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Prediction of spontaneous preterm delivery from maternal factors, obstetric history and placental perfusion and function at 11–13 weeks
Abstract
To develop a model for prediction of spontaneous delivery before 34 weeks based on maternal factors, placental perfusion and function at 11-13 weeks' gestation.
Two groups of studies: first, screening study of maternal characteristics, serum pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotrophin (β-hCG) and uterine artery pulsatility index (PI). Second, case-control studies of maternal serum or plasma concentration of placental growth factor (PlGF), placental protein 13 (PP13), a disintegrin and metalloprotease 12 (ADAM12), inhibin-A and activin-A. Regression analysis was used to develop a model for the prediction of spontaneous early delivery.
Spontaneous early delivery occurred in 365 (1.1%) of the 34 025 pregnancies. A model based on maternal factors could detect 38.2% of the preterm deliveries in women with previous pregnancies at or beyond 16 weeks and 18.4% in those without, at a false positive rate (FPR) of 10%. In the preterm delivery group, compared with unaffected pregnancies there were no significant differences in the markers of placental perfusion or function, except for PAPP-A which was reduced.
Patient-specific risk of preterm delivery is provided by maternal factors and obstetric history. Placental perfusion and function at 11-13 weeks are not altered in pregnancies resulting in spontaneous early delivery.
... Data from a variety of domains including patients' demographics, current and past obstetric history as well as social and past medical and surgical history was collected from the local hospital electronic medical records and pseudo-anonymised (Table 1). Initial domain selection was informed by previous published mathematical models as well as plausible pathophysiological pathways underlying sPTB [4,11]. ...
... To create the algorithm, data was standardised to be consistent across the index and control groups. Variables with multiple categories, for example substance misuse, were simplified for the algorithm and transformed into fewer categories such as alcohol (1), cannabis, heroin, or cocaine (2), mix of 1 and 2 (3) and/ or no misuse (4). Ethnicity was also reclassified into 7 categories based on the NHS self-reported available data including African, Asian, British, European, Latin American, Middle Eastern, and mixed (if 2 or more ethnicities selected). ...
... The average test's area under the receiver operating characteristic curve (AUC) and standard deviation were obtained. The predictive performance for sPTB was subsequently compared in a testing subset and also against a previous model by Beta et al. [4] which used demographic, obstetric data and placental and perfusion data collected during the first trimester. No formal comparison was made with the QUiPP app despite being a validated predictive model as the data inputted in the app must include sPTB history, gestational age, foetal fibronectin and/or cervical length, and therefore, it is not suitable to those regarded as low risk which was the case for most of our sPTB women [25]. ...
Background
Current predictive machine learning techniques for spontaneous preterm birth heavily rely on a history of previous preterm birth and/or costly techniques such as fetal fibronectin and ultrasound measurement of cervical length to the disadvantage of those considered at low risk and/or those who have no access to more expensive screening tools.
Aims and objectives
We aimed to develop a predictive model for spontaneous preterm delivery < 37 weeks using socio-demographic and clinical data readily available at booking -an approach which could be suitable for all women regardless of their previous obstetric history.
Methods
We developed a logistic regression model using seven feature variables derived from maternal socio-demographic and obstetric history from a preterm birth (n = 917) and a matched full-term (n = 100) cohort in 2018 and 2020 at a tertiary obstetric unit in the UK. A three-fold cross-validation technique was applied with subsets for data training and testing in Python® (version 3.8) using the most predictive factors. The model performance was then compared to the previously published predictive algorithms.
Results
The retrospective model showed good predictive accuracy with an AUC of 0.76 (95% CI: 0.71–0.83) for spontaneous preterm birth, with a sensitivity and specificity of 0.71 (95% CI: 0.66–0.76) and 0.78 (95% CI: 0.63–0.88) respectively based on seven variables: maternal age, BMI, ethnicity, smoking, gestational type, substance misuse and parity/obstetric history.
Conclusion
Pending further validation, our observations suggest that key maternal demographic features, incorporated into a traditional mathematical model, have promising predictive utility for spontaneous preterm birth in pregnant women in our region without the need for cervical length and/or fetal fibronectin.
... Това включва клинични симптоми като регулярни маточни контракции, активиране на мембраните (например спонтанна руптура на околоплодния мехур) и дилатация на маточната шийка [1,[3][4][5]. Етиологията на ПР е многокомпонентна и много автори смятат, че трябва да се разглежда като синдром, а не като изолирано заболяване или събитие [5][6][7]. Някои от етиологичните фактори са добре проучени, докато други все още предстои да бъдат напълно разбрани. Въпреки тези неясноти, патофизиологичната активация на раждането остава същата с вече изброените компоненти. ...
... По-възрастните пациентки са с повишен риск и поради коморбидитет, наднормено тегло и хормонален дисбаланс. Майчината възраст е независим рисков фактор за неблагоприятен акушерски изход [6,12]. Мултипаритетът също увеличава риска от ПР, като е оценено, че при пациенти примипара съществува риск за ПР в по-късни срокове, докато при наличие на едно предшестващо раждане -рискът е за по-ранен срок. ...
... В този ред на мисли, при скрининг за тези състояния и съответно програми за тяхното превантиране, се намаля и рискът от ПР [6]. Така при намалена честота на прееклампсия, ще се намали и процентът на усложненията в следствие от същата, което пък ще доведе до намаляване на ПР. ...
Преждевременното раждане оказва значително въздействие върху здравето на новороденото, което налага употребата на прогностични методи, за да се оценят рисковите бременни, които е възможно да родят по-рано, или да осигури спокойствие на жените, които са изложени на по-малък риск от настъпването на такова. Няма единна система за скрининг преди раждането с висока чувствителност, която ефективно разпознава жените с висок риск от прематурно раждане, но също така и с висока специфичност, за да се избегнат ненужни лечения и високите разходи за болничен престой. В ежедневната практика е необходим лесен и бърз тест за предвиждане на преждевременно раждане, а в допълнение и въвеждането на алгоритъм от методи за подобряване на клиничната прогноза. Настоящата публикация има за цел да представи и анализира познатите до момента методи за прогнозиране на предтерминно раждане.
... 8 There is some contradictory evidence as to whether women at high risk of developing pre-eclampsia are also at increased risk of spontaneous (s) and iatrogenic (i) preterm birth (PTB) for reasons other than pre-eclampsia and whether the incidence of these conditions is also reduced by prophylactic use of aspirin. [9][10][11][12][13] The objectives of this study are: first, to compare the predictive performance of the FMF triple test and NICE guidelines for sPTB and iPTB, and second, to examine the impact of prophylactic use of aspirin in the prevention of these pregnancy complications. ...
... 9 Another cohort study of 34 025 singleton pregnancies, investigating the value of various biomarkers of placental perfusion and function at 11-13 weeks of gestation, including UtA-PI and maternal serum pregnancy-associated plasma protein-A (PAPP-A), free βhuman chorionic gonadotrophin, PlGF, placental protein 13, ADAM12, inhibin-A and activin-A, in the prediction of sPTB at <34 weeks, reported that first, in the sPTB group, compared with unaffected pregnancies there were no significant differences in any of these biomarkers, except for PAPP-A which was reduced; and second, inclusion of these biomarkers did not improve the prediction of sPTB provided by maternal risk factors. 10 A smaller study of 11 437 women undergoing first-trimester screening for preterm preeclampsia by a combination of maternal risk factors, MAP, UtA-PI and PAPP-A, reported that in those with estimated risk of ≥1 in 50, compared with those with a risk <1 in 50, the odds ratio for iPTB was 6.0 (95% CI 4.29-8.43) and T A B L E 3 Incidence of each pregnancy complication in a population of 16 451 singleton pregnancies examined in SPREE 8 and detection rate with 95% confidence interval, in screening for preterm pre-eclampsia by the FMF triple test and NICE guidelines. ...
Objective
To report the predictive performance for preterm birth (PTB) of the Fetal Medicine Foundation (FMF) triple test and National Institute for health and Care Excellence (NICE) guidelines used to screen for pre‐eclampsia and examine the impact of aspirin in the prevention of PTB.
Design
Secondary analysis of data from the SPREE study and the ASPRE trial.
Setting
Multicentre studies.
Population
In SPREE, women with singleton pregnancies had screening for preterm pre‐eclampsia at 11–13 weeks of gestation by the FMF method and NICE guidelines. There were 16 451 pregnancies that resulted in delivery at ≥24 weeks of gestation and these data were used to derive the predictive performance for PTB of the two methods of screening. The results from the ASPRE trial were used to examine the effect of aspirin in the prevention of PTB in the population from SPREE.
Methods
Comparison of performance of FMF method and NICE guidelines for pre‐eclampsia in the prediction of PTB and use of aspirin in prevention of PTB.
Main outcome measure
Spontaneous PTB (sPTB), iatrogenic PTB for pre‐eclampsia (iPTB‐PE) and iatrogenic PTB for reasons other than pre‐eclampsia (iPTB‐noPE).
Results
Estimated incidence rates of sPTB, iPTB‐PE and iPTB‐noPE were 3.4%, 0.8% and 1.6%, respectively. The corresponding detection rates were 17%, 82% and 25% for the triple test and 12%, 39% and 19% for NICE guidelines, using the same overall screen positive rate of 10.2%. The estimated proportions prevented by aspirin were 14%, 65% and 0%, respectively.
Conclusion
Prediction of sPTB and iPTB‐noPE by the triple test was poor and poorer by the NICE guidelines. Neither sPTB nor iPTB‐noPE was reduced substantially by aspirin.
... An algorithm for the prediction of PTB with onset before 34 gestational weeks in the early stages of gestation exists that is based only on maternal characteristics (maternal age and BMI at early stages of gestation, racial origin, method of conception, and smoking during pregnancy) combined with previous obstetrics history [4]. It can identify, with a 10.0% false-positive rate (FPR), PTBs occurring before 34 gestational weeks in approximately 20% of nulliparous pregnancies and 38% of multiparous pregnancies [4]. ...
... An algorithm for the prediction of PTB with onset before 34 gestational weeks in the early stages of gestation exists that is based only on maternal characteristics (maternal age and BMI at early stages of gestation, racial origin, method of conception, and smoking during pregnancy) combined with previous obstetrics history [4]. It can identify, with a 10.0% false-positive rate (FPR), PTBs occurring before 34 gestational weeks in approximately 20% of nulliparous pregnancies and 38% of multiparous pregnancies [4]. This algorithm has been integrated into routine first-trimester prenatal screening performed within 11 and 13 gestational weeks and is currently used by the majority of Fetal Medicine Centres to calculate not only the risks for chromosomal aneuploidies (trisomy 21, trisomy 18, and trisomy 13) but also the risks for early preeclampsia (PE) with onset before 34 gestational weeks and fetal growth restriction (FGR) with onset before 37 gestational weeks (Astraia Obstetrics program) [5][6][7][8][9]. ...
The goal of the study was to establish an efficient first-trimester predictive model for any type of preterm birth before 37 gestational weeks (spontaneous preterm birth (PTB) or preterm prelabor rupture of membranes (PPROM)) in the absence of other pregnancy-related complications, such as gestational hypertension, preeclampsia, fetal growth restriction, or small for gestational age. The retrospective study was performed in the period from 11/2012 to 3/2020. Peripheral blood samples were collected from 6440 Caucasian individuals involving 41 PTB and 65 PPROM singleton pregnancies. A control group with 80 singleton term pregnancies was selected on the basis of equal sample-storage time. A combination of only six microRNAs (miR-16-5p, miR-21-5p, miR-24-3p, miR-133a-3p, miR-155-5p, and miR-210-3p; AUC 0.812, p < 0.001, 70.75% sensitivity, 78.75% specificity, cut-off > 0.652) could predict preterm delivery before 37 gestational weeks in early stages of gestation in 52.83% of pregnancies with a 10.0% FPR. This predictive model for preterm birth based on aberrant microRNA expression profile was further improved via implementation of maternal clinical characteristics (maternal age and BMI at early stages of gestation, infertility treatment with assisted reproductive technology, occurrence of preterm delivery before 37 gestational weeks in previous pregnancy(ies), and presence of any kind of autoimmune disease (rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, type 1 diabetes mellitus, or other autoimmune disease)). With this model, 69.81% of pregnancies destined to deliver before 37 gestational weeks were identified with a 10.0% FPR at early stages of gestation. When other clinical variables as well as those mentioned above—such as positive first-trimester screening for early preeclampsia with onset before 34 gestational weeks and/or fetal growth restriction with onset before 37 gestational weeks using the Fetal Medicine Foundation algorithm, as well as positive first-trimester screening for spontaneous preterm birth with onset before 34 gestational weeks using the Fetal Medicine Foundation algorithm—were added to the predictive model for preterm birth, the predictive power was even slightly increased to 71.70% with a 10.0% FPR. Nevertheless, we prefer to keep the first-trimester screening for any type of preterm birth occurring before 37 gestational weeks in the absence of other pregnancy-related complications as simple as possible.
... It uses this information to more accurately, and automatically, assess a woman's risk of preterm birth and pregnancy complications such as preeclampsia and fetal compromise which can lead to stillbirth. It does this by utilising three validated algorithms for risk assessment and clinical decision support; one for placental disorders (preeclampsia, stillbirth) [11] and two for preterm birth, one at the beginning of pregnancy [12] and the other during pregnancy if women present with symptoms of threatened preterm labour [13]. The tool not only provides individualised risk assessment at the point of care, but also recommends care pathways which are based on best practice and current national guidance. ...
... All used maternal characteristics, medical and previous obstetric history. The only algorithm calculating risk of preterm birth before 34 weeks was selected [12]. The algorithm had also been externally validated in a Dutch cohort [18]. ...
Background
Disparities in stillbirth and preterm birth persist even after correction for ethnicity and social deprivation, demonstrating that there is wide geographical variation in the quality of care. To address this inequity, Tommy’s National Centre for Maternity Improvement developed the Tommy’s Clinical Decision Tool, which aims to support the provision of “the right care at the right time”, personalising risk assessment and care according to best evidence. This web-based clinical decision tool assesses the risk of preterm birth and placental dysfunction more accurately than current methods, and recommends best evidenced-based care pathways in a format accessible to both women and healthcare professionals. It also provides links to reliable sources of pregnancy information for women. The aim of this study is to evaluate implementation of Tommy’s Clinical Decision Tool in four early-adopter UK maternity services, to inform wider scale-up.
Methods
The Tommy’s Clinical Decision Tool has been developed involving maternity service users and healthcare professionals in partnership. This mixed-methods study will evaluate: maternity service user and provider acceptability and experience; barriers and facilitators to implementation; reach (whether particular groups are excluded and why), fidelity (degree to which the intervention is delivered as intended), and unintended consequences. Data will be gathered over 25 months through interviews, focus groups, questionnaires and through the Tommy’s Clinical Decision Tool itself. The NASSS framework (Non-adoption or Abandonment of technology by individuals and difficulties achieving Scale-up, Spread and Sustainability) will inform data analysis.
Discussion
This paper describes the intervention, Tommy’s Clinical Decision Tool, according to TiDIER guidelines, and the protocol for the early adopter implementation evaluation study. Findings will inform future scale up.
Trial registration
This study was prospectively registered on the ISRCTN registry no. 13498237 , on 31 st January 2022.
... hCG. Evidence suggesting an association between maternal levels of hCG and sPTB is inconclusive [14,20,44,50], though some studies suggest that low levels of hCG were associated with increased risk of sPTB (OR range 0.8-2.0) [43, 45,49,78] and that high levels of hCG independently decreased risk of sPTB [77]. ...
... The predictive value of alpha-fetoprotein (AFP) and multi-marker models was higher in parous populations as compared to nulliparous [14,19,57], indicating that these two populations may have distinct physiology of sPTB and may require distinct approaches to prediction. Other biomarkers from maternal serum screen tests, pregnancy associated plasma protein (PAPP-A) and human chorionic gonadotropin (B-hCG) were similarly more associated with sPTB in parous populations with previous sPTB as compared to nulliparous populations [20,77]. ...
Introduction
The ability to predict spontaneous preterm birth (sPTB) prior to labour onset is a challenge, and it is currently unclear which biomarker(s), may be potentially predictive of sPTB, and whether their predictive power has any utility. A systematic review was conducted to identify maternal blood biomarkers of sPTB.
Methods
This study was conducted according to PRISMA protocol for systematic reviews. Four databases (MEDLINE, EMBASE, CINAHL, Scopus) were searched up to September 2021 using search terms: “preterm labor”, “biomarker” and “blood OR serum OR plasma”. Studies assessing blood biomarkers prior to labour onset against the outcome sPTB were eligible for inclusion. Risk of bias was assessed based on the Newcastle Ottawa scale. Increased odds of sPTB associated with maternal blood biomarkers, as reported by odds ratios (OR), or predictive scores were synthesized. This review was not prospectively registered.
Results
Seventy-seven primary research articles met the inclusion criteria, reporting 278 unique markers significantly associated with and/or predictive of sPTB in at least one study. The most frequently investigated biomarkers were those measured during maternal serum screen tests for aneuploidy, or inflammatory cytokines, though no single biomarker was clearly predictive of sPTB based on the synthesized evidence. Immune and signaling pathways were enriched within the set of biomarkers and both at the level of protein and gene expression.
Conclusion
There is currently no known predictive biomarker for sPTB. Inflammatory and immune biomarkers show promise, but positive reporting bias limits the utility of results. The biomarkers identified may be more predictive in multi-marker models instead of as single predictors. Omics-style studies provide promising avenues for the identification of novel (and multiple) biomarkers. This will require larger studies with adequate power, with consideration of gestational age and the heterogeneity of sPTB to identify a set of biomarkers predictive of sPTB.
... An algorithm for the prediction of spontaneous preterm delivery in the first trimester of gestation (between 11 and 13 weeks) based on the combination of maternal characteristics, obstetrics history, biochemical markers such as free beta human chorionic gonadotrophin (beta-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor 3 of 21 (PIGF), placental protein 13 (PP13), a disintegrin and metalloprotease 12 (ADAM12), inhibin-A, activin-A, and Doppler ultrasound parameter (mean uterine artery pulsatility index) was not superior over a model based on maternal factors and obstetrics history only [30]. The screening based on maternal factors and obstetrics history was able to identify at 10.0% FPR spontaneous early preterm delivery in about 20% nulliparous women and 38% multiparous women [30]. ...
... An algorithm for the prediction of spontaneous preterm delivery in the first trimester of gestation (between 11 and 13 weeks) based on the combination of maternal characteristics, obstetrics history, biochemical markers such as free beta human chorionic gonadotrophin (beta-hCG), pregnancy-associated plasma protein-A (PAPP-A), placental growth factor 3 of 21 (PIGF), placental protein 13 (PP13), a disintegrin and metalloprotease 12 (ADAM12), inhibin-A, activin-A, and Doppler ultrasound parameter (mean uterine artery pulsatility index) was not superior over a model based on maternal factors and obstetrics history only [30]. The screening based on maternal factors and obstetrics history was able to identify at 10.0% FPR spontaneous early preterm delivery in about 20% nulliparous women and 38% multiparous women [30]. This model was integrated into more complex Astraia Obstetrics programme, which has been currently used by most Fetal Medicine Centres to calculate the risks for trisomy 21, 18 and 13, preeclampsia, and fetal growth restriction during the first trimester of gestation [31][32][33][34][35]. ...
The aim of the study was to determine if aberrant expression profile of cardiovascular disease associated microRNAs would be able to predict within 10 to 13 weeks of gestation preterm delivery such as spontaneous preterm birth (PTB) or preterm prelabor rupture of membranes (PPROM) in the absence of other pregnancy-related complications (gestational hypertension, preeclampsia, fetal growth restriction, or small for gestational age). In addition, we assessed if aberrant expression profile of cardiovascular disease associated microRNAs would be able to predict preterm delivery before and after 34 weeks of gestation. The retrospective study was performed within the period November 2012 to March 2020. Whole peripheral blood samples were collected from 6440 Caucasian individuals involving 41 PTB and 65 PPROM singleton pregnancies. A control group, 80 singleton term pregnancies, was selected on the base of equal sample storage time. Gene expression of 29 selected cardiovascular disease associated microRNAs was studied using real-time RT-PCR. Downregulation of miR-16-5p, miR-20b-5p, miR-21-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-126-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, miR-221-3p and miR-342-3p was observed in pregnancies with preterm delivery before 37 (≤36 + 6/7) weeks of gestation. Majority of downregulated microRNAs (miR-16-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, and miR-342-3p) was associated with preterm delivery occurring before 37 (≤36 + 6/7) weeks of gestation. The only miR-210-3p was downregulated in pregnancies with preterm delivery before 34 (≤33 + 6/7) weeks of gestation. The type of preterm delivery also had impact on microRNA gene expression profile. Downregulation of miR-24-3p, miR-92a-3p, miR-155-5p, and miR-210-3p was a common feature of PTB and PPROM pregnancies. Downregulation of miR-16-5p, miR-20b-5p, miR-26a-5p, miR-126-3p, miR-133a-3p, miR-146a-5p, miR-221-3p, and miR-342-3p appeared just in PTB pregnancies. No microRNA was uniquely dysregulated in PPROM pregnancies. The combination of 12 microRNAs (miR-16-5p, miR-20b-5p, miR-21-5p, miR-24-3p, miR-26a-5p, miR-92a-3p, miR-133a-3p, miR-145-5p, miR-146a-5p, miR-155-5p, miR-210-3p, and miR-342-3p, AUC 0.818, p < 0.001, 74.53% sensitivity, 75.00% specificity, cut off > 0.634) equally as the combination of 6 microRNAs (miR-16-5p, miR-21-5p, miR-24-3p, miR-133a-3p, miR-155-5p, and miR-210-3p, AUC 0.812, p < 0.001, 70.75% sensitivity, 78.75% specificity, cut off > 0.652) can predict preterm delivery before 37 weeks of gestation in early stages of gestation in 52.83% pregnancies at 10.0% FPR. Cardiovascular disease associated microRNAs represent promising biomarkers with very good diagnostical potential to be implemented into the current routine first trimester screening programme to predict preterm delivery.
... At present, clinicians tend to use ad hoc prediction models generated by adding known historical or demographic risk factors to ultrasound findings to assign levels of risk to a pregnancy; however, this approach is not validated and prediction models have tended to perform poorly. 47 Our results provide evidence that twin pregnancy confers a high a priori risk of SPTB, and that a shorter cervix is associated with a higher risk. Further analysis of this dataset may allow precise risk estimates at various cervical length cutoffs, however, we have already cautioned extensively against arbitrary dichotomisation. ...
Objective
To quantify the prognostic value of mid-trimester cervical length for spontaneous preterm birth in asymptomatic women with twin pregnancy and to assess whether other factors may modify any association.
Designs
A two stage meta-analysis of individual participant data in a Cox proportional hazard model was performed using cervical length as a continuous variable.
Data sources
Medline, Embase, Cochrane, and LILACS, among others, were searched to identify eligible studies; the search was from 1 January 2000 to 30 September 2020. Risk of bias was assessed with the QUIPS tool. Studies were from eight countries between 2001 and 2018.
Eligibility criteria
Individual participant data were sought for eligible studies that reported mid-trimester (defined between 16 and 26 weeks) transvaginal sonographic cervical length and also gestational age at birth in asymptomatic women with twin pregnancy. The primary outcome was spontaneous preterm birth before 37 weeks.
Results
Among 29 eligible studies, authors of 17 studies provided individual participant data for 6437 women with a twin pregnancy (69.1% of individual participant data). Mean cervical length measurement was 39 mm (SD=9, range 1-74 mm). 2889 women (44.9%) delivered before 37 weeks' gestation, and 934 (14.9%) delivered before 34 weeks. Each 1 mm increase in cervical length was associated with a 4.0% reduction in the rate of spontaneous preterm birth before 37 weeks (hazard ratio 0.96 (95% confidence interval 0.95 to 0.97)), and a 6.8% reduction in the rate of spontaneous preterm birth before 34 weeks' gestation (0.93 (0.92 to 0.95)). The prognostic value remained stable in models adjusting for different sets of variables.
Conclusion
The prognostic value of cervical length for spontaneous preterm birth in twin pregnancy is on a continuous scale. No specific cervical length has been identified that can reliably predict or exclude all spontaneous preterm births.
Study registration
CRD42020146987.
... The next assessment is at 20-22 weeks' gestation for the examination of foetal growth and anatomy, placental localisation, uterine artery Doppler to assess impedance to blood flow across the placenta and cervical length measurement [15,16]. All pregnancies are offered a risk assessment for iatrogenic and spontaneous preterm delivery based on an assessment of maternal factors, obstetric and gynaecology history, cervical length assessment and uterine artery Doppler [15,17,18]. Those that are deemed to be at high chance for spontaneous prematurity are referred to the preterm birth clinic at 14-15 weeks' gestation and those at risk of iatrogenic preterm delivery due to placental insufficiency are referred to the placental disorder clinic. ...
Objectives: The aim of this study was to investigate the factors associated with the prediction of perinatal survival in pregnancies with extreme preterm delivery between 24⁺⁰ and 27⁺⁶ weeks’ gestation. Methods: This screening cohort study was undertaken at a large tertiary obstetric and neonatal unit in the United Kingdom. We included singleton pregnancies that booked and delivered at our hospital. Logistic regression analysis was carried out to determine risks of complications in pregnancies delivering preterm after adjusting for maternal and pregnancy characteristics. Effect sizes were expressed as absolute risks (ARs) and odds ratios (ORs) (95% confidence intervals [CI]). Results: The study population included 53,649 singleton pregnancies, including 139 (0.3%) with preterm delivery between 24⁺⁰ and 27⁺⁶ weeks and 47,006 (99.7%) with term delivery ≥37 weeks. Multivariate regression analysis demonstrated that there was a significant contribution of uterine artery pulsatility index (UtA-PI) and cervical length, but not of maternal factors, in the prediction of preterm delivery <28 weeks. The risk of neonatal death and intact neurological survival in pregnancies delivering <28 weeks was 11.5% and 79.1%, respectively. Caesarean compared to vaginal delivery and female compared to male neonates were associated with a lower incidence of neurological morbidity (6.1% vs. 19.3%; p = 0.016 and 13.1% vs. 26.9%; p = 0.036, respectively). In the prediction of intact perinatal survival, the only significant variable was gestational age at delivery, with survival rates of about 50%, 65%, 80% and 90% at 24, 25, 26 and 27 weeks, respectively. Conclusions: In pregnancies with extreme preterm delivery between 24⁺⁰ and 27⁺⁶ weeks, caesarean compared to vaginal delivery and female compared to male neonates are associated with a lower incidence of neurological morbidity. The only significant factor in the prediction of intact perinatal survival is gestational age at delivery.
... Ехографското изследване отдавна е идентифицирано като един от най-добрите предиктори за ПР. Измерването на дължината на маточната шийка е найшироко използван в съвременната клинична практика метод за прогнозирането на предстоящо раждане [6][7]. ...
Преждевременното раждане е сложен медицински проблем, който се дължи на множество етиологични фактори, включително генетични, инфекциозни, имунологични и екологични влияния. Прогнозирането и предотвратяването на раждане преди 37-та гестационна седмица представлява значително предизвикателство в пренаталната медицина поради разнообразието от етиологични фактори. Предвестниците на предтерминно раждане, които сигнализират за възможността от появата му, са от изключителна важност за предотвратяването му. Ехографското изследване отдавна е идентифицирано като един от най-добрите предиктори за преждевременно раждане. Измерването на дължината на маточната шийка е най-широко използван в съвременната клинична практика метод за прогнозирането на предстоящо раждане. Настоящата публикация има за цел да представи и анализира методите за прогнозиране на преждевременно раждане.
... The overall risk of bias in eight of the nine external validations was low [5,63]. The overall concern regarding applicability was low for seven of the eleven [33][34][35][36][37]63] developed models and in all nine external validations [5,53]. ...
Background
Early risk stratification can facilitate timely interventions for adverse pregnancy outcomes, including preeclampsia (PE), small‐for‐gestational‐age neonates (SGA), spontaneous preterm birth (sPTB) and gestational diabetes mellitus (GDM).
Objectives
To perform a systematic review and meta‐analysis of first‐trimester prediction models for adverse pregnancy outcomes.
Search Strategy
The PubMed database was searched until 6 June 2024.
Selection Criteria
First‐trimester prediction models based on maternal characteristics were included. Articles reporting on prediction models that comprised biochemical or ultrasound markers were excluded.
Data Collection and Analysis
Two authors identified articles, extracted data and assessed risk of bias and applicability using PROBAST.
Main results
A total of 77 articles were included, comprising 30 developed models for PE, 15 for SGA, 11 for sPTB and 35 for GDM. Discriminatory performance in terms of median area under the curve (AUC) of these models was 0.75 [IQR 0.69–0.78] for PE models, 0.62 [0.60–0.71] for SGA models of nulliparous women, 0.74 [0.72–0.74] for SGA models of multiparous women, 0.65 [0.61–0.67] for sPTB models of nulliparous women, 0.71 [0.68–0.74] for sPTB models of multiparous women and 0.71 [0.67–0.76] for GDM models. Internal validation was performed in 40/91 (43.9%) of the models. Model calibration was reported in 21/91 (23.1%) models. External validation was performed a total of 96 times in 45/91 (49.5%) of the models. High risk of bias was observed in 94.5% of the developed models and in 58.3% of the external validations.
Conclusions
Multiple first‐trimester prediction models are available, but almost all suffer from high risk of bias, and internal and external validations were often not performed. Hence, methodological quality improvement and assessment of the clinical utility are needed.
... Chronic hypertension 15 15 Gestational diabetes mellitus 10 analysis, model performance calculated using AUC ranged within 0.61-0.71 [23][24][25][26][27][28] . The types of birth used as the outcome variables were SPTBs and PTBs. ...
Preterm birth (PTB) is one of the most common and serious complications of pregnancy, leading to mortality and severe morbidities that can impact lifelong health. PTB could be associated with various maternal medical condition and dental status including periodontitis. The purpose of this study was to identify major predictors of PTB among clinical and dental variables using machine learning methods. Prospective cohort data were obtained from 60 women who delivered singleton births via cesarean section (30 PTB, 30 full-term birth [FTB]). Dependent variables were PTB and spontaneous PTB (SPTB). 15 independent variables (10 clinical and 5 dental factors) were selected for inclusion in the machine learning analysis. Random forest (RF) variable importance was used to identify the major predictors of PTB and SPTB. Shapley additive explanation (SHAP) values were calculated to analyze the directions of the associations between the predictors and PTB/SPTB. Major predictors of PTB identified by RF variable importance included pre-pregnancy body mass index (BMI), modified gingival index (MGI), preeclampsia, decayed missing filled teeth (DMFT) index, and maternal age as in top five rankings. SHAP values revealed positive correlations between PTB/SPTB and its major predictors such as premature rupture of the membranes, pre-pregnancy BMI, maternal age, and MGI. The positive correlations between these predictors and PTB emphasize the need for integrated medical and dental care during pregnancy. Future research should focus on validating these predictors in larger populations and exploring interventions to mitigate these risk factors.
... Some calculators for preterm birth are available to screen preterm birth, but these calculators are not useful in clinical practice. (15,16) Creating easy algorithms to predict preterm birth is important because the costs involved are tremendous. (7) Strategies joining cervical ultrasound, clinical aspects, and demographic characteristics are strongly encouraged by experts. ...
Objective
This study aims to create a new screening for preterm birth < 34 weeks after gestation with a cervical length (CL) ≤ 30 mm, based on clinical, demographic, and sonographic characteristics.
Methods
This is a post hoc analysis of a randomized clinical trial (RCT), which included pregnancies, in middle-gestation, screened with transvaginal ultrasound. After observing inclusion criteria, the patient was invited to compare pessary plus progesterone (PP) versus progesterone only (P) (1:1). The objective was to determine which variables were associated with severe preterm birth using logistic regression (LR). The area under the curve (AUC), sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were calculated for both groups after applying LR, with a false positive rate (FPR) set at 10%.
Results
The RCT included 936 patients, 475 in PP and 461 in P. The LR selected: ethnics white, absence of previous curettage, previous preterm birth, singleton gestation, precocious identification of short cervix, CL < 14.7 mm, CL in curve > 21.0 mm. The AUC (CI95%), sensitivity, specificity, PPV, and PNV, with 10% of FPR, were respectively 0.978 (0.961-0.995), 83.4%, 98.1%, 83.4% and 98.1% for PP < 34 weeks; and 0.765 (0.665-0.864), 38.7%, 92.1%, 26.1% and 95.4%, for P < 28 weeks.
Conclusion
Logistic regression can be effective to screen preterm birth < 34 weeks in patients in the PP Group and all pregnancies with CL ≤ 30 mm.
... PTB is the most prevalent complication in TwP, responsible for significant perinatal morbidity and mortality [1][2][3]. In singleton pregnancies, maternal serum biomarkers such as PAPP-A (pregnancyassociated plasma protein-A) and β-hCG (β-human chorionic gonadotropin) used for first-trimester screening have been associated with adverse pregnancy outcomes such as pre-eclampsia (PE), FGR, PTB [4][5][6][7][8][9]. However, for twin pregnancies, comprehensive data on first-trimester biomarkers is lacking and some previous reports have conflicting results [10,11]. ...
Purpose
This study aimed to determine the association of first-trimester maternal serum biomarkers with preterm birth (PTB), fetal growth restriction (FGR) and hypertensive disorders of pregnancy (HDP) in twin pregnancies.
Methods
This is a retrospective cohort study of twin pregnancies followed at Maternidade Dr. Alfredo da Costa, Lisbon, Portugal, between January 2010 and December 2022. We included women who completed first-trimester screening in our unit and had ongoing pregnancies with two live fetuses, and delivered after 24 weeks. Maternal characteristics, pregnancy-associated plasma protein-A (PAPP-A) and β-human chorionic gonadotropin (β-hCG) levels were analyzed for different outcomes: small for gestational age (SGA), gestational hypertension (GH), early and late-onset pre-eclampsia (PE), as well as the composite outcome of PTB associated with FGR and/or HDP. Univariable, multivariable logistic regression analyses and receiver-operating characteristic curve were used.
Results
466 twin pregnancies met the inclusion criteria. Overall, 185 (39.7%) pregnancies were affected by SGA < 5th percentile and/or HDP. PAPP-A demonstrated a linear association with gestational age at birth and mean birth weight. PAPP-A proved to be an independent risk factor for SGA and PTB (< 34 and < 36 weeks) related to FGR and/or HDP. None of the women with PAPP-A MoM > 90th percentile developed early-onset PE or PTB < 34 weeks.
Conclusion
A high serum PAPP-A (> 90th percentile) ruled out early-onset PE and PTB < 34 weeks. Unless other major risk factors for hypertensive disorders are present, these women should not be considered candidates for aspirin prophylaxis. Nevertheless, close monitoring of all TwP for adverse obstetric outcomes is still recommended.
... It is considered one of the main causes of maternal morbidity, and it refers to the presence or occurrence of diseases, conditions or health complications Numerous studies have identified the role of oxidative stress and cytokines in the pathogenesis of preterm birth [7,8]. ...
Introduction. Premature birth can occur at any age; however, it is important to note that the risk of preterm birth can vary
based on several factors, including the mother’s medical history, general health, and lifestyle. There is thought to be a relationship between maternal age and the risk of preterm birth, although the exact nature of this relationship may vary. At the
same time, it is considered for ages over 35, an increased risk factor for the evolution of pregnancies with complications.
Pregnant women over 35 face a higher risk of premature birth. This increased risk may be associated with age-related factors such as underlying health conditions, higher rates of multiple pregnancies (due to fertility treatments), and potential
placental dysfunction.
Material and methods. In the given study, the biomarkers IL-6, IL-8, IL-10, IL-12, SDF-1α and VEGF in amniotic fluid (AF)
and maternal blood were investigated, considering the above as predictive of premature birth outcome. At the same time, the
oxidative stress status of maternal blood and amniotic fluid collected in the second trimester of pregnancy was identified.
Results. In the research, we obtained statistically significant increases in the biomarkers AAT-isopropyl, G-GTP, HPL-isopropyl from the amniotic fluid taken from pregnant women over 35 years of age in the second trimester of pregnancy in
those pregnant women who had a preterm birth. In the serum of pregnant women with premature birth, an increase in
the concentration of carnosine-histidine peptides, G-GTP, GR and SH (thiol) groups was identified, and the decrease in the
values of SDF 1α, HPL – hexane and IL-12 were statistically significant in the serum pregnant women compared to that of
the amniotic fluid.
Identifying the values of biochemical mediators during pregnancy can be a method of predictive diagnosis
Conclusions. Our study shows the relationship between some concentrations of oxidative stress biomarkers (AAT-isopropyl, HPL-isopropyl and G-GTP, IL-12) in amniotic fluid, and values of (Carnosine Histidine Peptide, GR and SH and SDF-1α)
in the serum of pregnant women, in the second trimester of pregnancy.
Keywords: premature birth, preterm delivery, risk factors, pregnancy over the age of 35 years, cytokines, inflammation,
biomarkers, IL-6, IL-8, IL-10, IL-12, SDF-1α, VEGF, oxidative stress, amniotic fluid.
... Beta et al. [4] has created a similar screening method based on maternal characteristics, intending to associate serum markers, but without sonographic variables. The principal variables selected were previous PTB 34-36 weeks (OR 2.980 CI95% 1.887 À 4.704; p < .0001), ...
Objective
The objective of this study is to create a new screening for spontaneous preterm birth (sPTB) based on artificial intelligence (AI).
Methods
This study included 524 singleton pregnancies from 18th to 24th-week gestation after transvaginal ultrasound cervical length (CL) analyzes for screening sPTB < 35 weeks. AI model was created based on the stacking-based ensemble learning method (SBELM) by the neural network, gathering CL < 25 mm, multivariate unadjusted logistic regression (LR), and the best AI algorithm. Receiver Operating Characteristics (ROC) curve to predict sPTB < 35 weeks and area under the curve (AUC), sensitivity, specificity, accuracy, predictive positive and negative values were performed to evaluate CL < 25 mm, LR, the best algorithms of AI and SBELM.
Results
The most relevant variables presented by LR were cervical funneling, index straight CL/internal angle inside the cervix (≤ 0.200), previous PTB < 37 weeks, previous curettage, no antibiotic treatment during pregnancy, and weight (≤ 58 kg), no smoking, and CL < 30.9 mm. Fixing 10% of false positive rate, CL < 25 mm and SBELM present, respectively: AUC of 0.318 and 0.808; sensitivity of 33.3% and 47,3%; specificity of 91.8 and 92.8%; positive predictive value of 23.1 and 32.7%; negative predictive value of 94.9 and 96.0%. This machine learning presented high statistical significance when compared to CL < 25 mm after T-test (p < .00001).
Conclusion
AI applied to clinical and ultrasonographic variables could be a viable option for screening of sPTB < 35 weeks, improving the performance of short cervix, with a low false-positive rate.
... Despite extensive efforts, only limited progress has been made in the early identification of women at risk to develop sPTD. Thus far, a predictive model that combines well-known risk factors including maternal age, maternal BMI, racial origin, maternal behaviors, spontaneous or assisted conception and prior history of sPTD has been shown to identify only 18% of nulliparous and 38% of parous women at risk at a screenpositive rate of 10% [6]. Prediction rate may increase to up to of 54.8% by combining a priori risk factors with the measurement of cervical length [7]. ...
Objective
Identification of differentially expressed proteins (DEPs) in first trimester maternal plasma between pregnant women with a subsequent spontaneous moderate/late Preterm Delivery (sPTD) and women who delivered at term. The sPTD group consisted of women who delivered between 32°/7 and 366/7 weeks of gestation.
Methods
Isobaric tags for relative and absolute quantification (iTRAQ) coupled with LC–MS/MS was used for the analysis of five first trimester maternal plasma samples obtained from women with a subsequent moderate/late preterm sPTD and five women with term deliveries. Enzyme-linked immunosorbent assay (ELISA) was further applied in an independent cohort of 29 sPTD cases and 29 controls to verify the expression levels of selected proteins.
Results
236 DEPs, mainly linked to coagulation and complement cascade, were identified in first trimester maternal plasma obtained from the sPTD group. Decreased levels of selected proteins, namely, VCAM-1, SAA, and Talin-1, were further confirmed using ELISA, highlighting their potential as candidate predictive biomarkers for sPTD at32°/7 and 366/7 weeks of gestation.
Conclusion
First trimester maternal plasma proteomic analysis revealed protein changes associated with subsequent moderate/late preterm sPTD.
... It is considered one of the main causes of maternal morbidity, and it refers to the presence or occurrence of diseases, conditions or health complications Numerous studies have identified the role of oxidative stress and cytokines in the pathogenesis of preterm birth [7,8]. ...
Introduction. Premature birth can occur at any age; however, it is important to note that the risk of preterm birth can vary based on several factors, including the mother’s medical history, general health, and lifestyle. There is thought to be a relationship between maternal age and the risk of preterm birth, although the exact nature of this relationship may vary. At the same time, it is considered for ages over 35, an increased risk factor for the evolution of pregnancies with complications. Pregnant women over 35 face a higher risk of premature birth. This increased risk may be associated with age-related factors such as underlying health conditions, higher rates of multiple pregnancies (due to fertility treatments), and potential placental dysfunction. Material and methods. In the given study, the biomarkers IL-6, IL-8, IL-10, IL-12, SDF-1α and VEGF in amniotic fluid (AF) and maternal blood were investigated, considering the above as predictive of premature birth outcome. At the same time, the oxidative stress status of maternal blood and amniotic fluid collected in the second trimester of pregnancy was identified. Results. In the research, we obtained statistically significant increases in the biomarkers AAT-isopropyl, G-GTP, HPL-isopropyl from the amniotic fluid taken from pregnant women over 35 years of age in the second trimester of pregnancy in those pregnant women who had a preterm birth. In the serum of pregnant women with premature birth, an increase in the concentration of carnosine-histidine peptides, G-GTP, GR and SH (thiol) groups was identified, and the decrease in the values of SDF 1α, HPL – hexane and IL-12 were statistically significant in the serum pregnant women compared to that of the amniotic fluid. Identifying the values of biochemical mediators during pregnancy can be a method of predictive diagnosis Conclusions. Our study shows the relationship between some concentrations of oxidative stress biomarkers (AAT-isopropyl, HPL-isopropyl and G-GTP, IL-12) in amniotic fluid, and values of (Carnosine Histidine Peptide, GR and SH and SDF-1α) in the serum of pregnant women, in the second trimester of pregnancy.
... Despite the existence of strategies for the prevention of PTB such as cervical cerclage [9,10] and progesterone administration [11][12][13], premature birth rates have not declined. This fact might be explained in part by the multifactorial etiology of PTB and by the inadequate selection of patients at increased risk [14]. ...
Background. Studies have identified a trend towards suboptimal birth outcomes, including preterm birth (PTB), in women who experience psychological adversities (stress, depression, domestic violence, and low social support) during pregnancy. Objective. To evaluate the association of stress, depression, domestic violence, and low social support with PTB. Methods. This is a retrospective cohort study that used data of women assessed between February 2011 and February 2012. The primary outcome of the study was the occurrence of spontaneous PTB < 37 weeks of gestational age. The pregnant women included were evaluated at two different time points: prenatal (between 22 and 25 weeks) and at birth. Sociodemographic data, obstetric history, perceived stress, depression, violence, and social support were collected with a questionnaire and subsequently evaluated and analyzed. Univariate and multivariate log-binomial regression models were constructed to assess the effects of the variables collected on the presence of spontaneous PTB. The SAS 9.3 program was used for all analyses, assuming statistical significance at p < 0:05 and a power of the test of 80%. Results. A total of 1,370 women were included in the study. The prevalence of PTB was 9.1%. Log-binomial analysis revealed an association between the following characteristics and PTB: smoking (RR 1.64, 95% CI: 1.10-2.44), severe stress (RR 1.82, 95% CI: 1.21-2.73), three or more stressful life events (RR 1.65, 95% CI: 1.05-2.59), and being probably depressed (RR 1.49, 95% CI: 1.02-2.18). However, these associations did not remain significant after multivariate analysis. Conclusion. Evidence on the specific effects of depression, violence, anxiety, and stress on birth outcomes remains unclear and at times conflicting. Our results showed no association of the studied parameters with an increased risk of prematurity.
... Several algorithms for the prediction of preterm birth, based on maternal risk factors, ultrasound markers, and serum biomarkers, have been evaluated in the current literature [8,9]. Among the most commonly associated maternal risk factors for PTB are the following: age, ethnicity, obesity, smoking during pregnancy, assisted reproductive techniques, genital and urinary tract infections, autoimmune disorders, thrombotic disorders, gestational diabetes and preeclampsia, and personal history of adverse pregnancy outcomes (recurrent pregnancy loss, history of PTB, etc.) [10][11][12][13][14]. ...
(1) Background: Cervical elastography is a new concept that could allow clinicians to assess cervical consistency in various clinical scenarios. We aimed to evaluate the predictive performance of the strain ratio (SR) at the level of the internal os, either individually or in combination with other parameters, in the prediction of spontaneous preterm birth (PTB) at various gestational ages. (2) Methods: This prospective study included 114 pregnant patients with a high-risk profile for PTB who underwent cervical elastography during the second trimester. Clinical and paraclinical data were assessed using univariate analysis, logistic regression, and sensitivity analysis. (3) Results: The SR achieved an area under the receiver operating curve (AUROC) value of 0.850, a sensitivity of 85.71%, and a specificity of 84.31% in the prediction of PTB before 37 weeks of gestation. The combined model showed superior results in terms of accuracy (AUROC = 0.938), sensitivity (92.31%), and specificity (95.16%). When considering PTB subtypes, the highest AUROC value (0.80) and accuracy (95.61%) of this marker were achieved in the prediction of extremely preterm birth, before 28 weeks of gestation. (4) Conclusions: The SR achieved an overall good predictive performance in the prediction of PTB and could be further evaluated in various cohorts of patients.
... Effective screening for PTB can be achieved by combining maternal history, demographic characteristics [4], and cervical length (CL) on the second-trimester scan [5]. The most efficient isolated marker for PTB is the CL in a transvaginal ultrasound (TVS) performed between 20 and 24 weeks [6,7]. ...
... Mothers who are smokers were more likely to experience the adverse birth outcome of preterm birth compared to non-smokers. This is consistent with previous studies in the US, UK and Brazil that had shown the risk of PB is higher in smokers [57][58][59]. Our result is also in line with a recent systematic review and meta-analysis [60], in which smoking, was identified as a risk factor where smoking in pregnancy increased the risk of preterm birth. ...
Background
Air pollution and several prenatal factors, such as socio-demographic, behavioural, physical activity and clinical factors influence adverse birth outcomes. The study aimed to investigate the impact of ambient air pollution exposure during pregnancy adjusting prenatal risk factors on adverse birth outcomes among pregnant women in MACE birth cohort.
Methods
Data for the study was obtained from the Mother and Child in the Environment (MACE) birth cohort study in Durban, South Africa from 2013 to 2017. Land use regression models were used to determine household level prenatal exposure to PM 2.5 , SO 2 and NOx. Six hundred and fifty-six births of pregnant females were selected from public sector antenatal clinics in low socio-economic neighbourhoods. We employed a Generalised Structural Equation Model with a complementary log–log-link specification.
Results
After adjustment for potential prenatal factors, the results indicated that exposure to PM 2.5 was found to have both significant direct and indirect effects on the risk of all adverse birth outcomes. Similarly, an increased level of maternal exposure to SO 2 during pregnancy was associated with an increased probability of being small for gestational age. Moreover, preterm birth act a mediating role in the relationship of exposure to PM 2.5 , and SO 2 with low birthweight and SGA.
Conclusions
Prenatal exposure to PM 2.5 and SO 2 pollution adversely affected birth outcomes after controlling for other prenatal risk factors. This suggests that local government officials have a responsibility for better control of air pollution and health care providers need to advise pregnant females about the risks of air pollution during pregnancy.
... Despite extensive efforts, screening strategies to accurately predict sPTD are still unsatisfactory. Currently, the most effective predictive tool combines well-known risk factors including maternal age, maternal BMI, racial origin, maternal behavior, spontaneous or assisted conception and prior history of sPTD, resulting in the identification of~18% of nulliparous and 38% of parous sPTD cases, with a 10% false positive rate [5]. The prediction rate has been shown to increase by 54.8% by combining a priori risk factors with the measurement of cervical length [6]. ...
Spontaneous Preterm Delivery (sPTD) is one of the leading causes of perinatal mortality and morbidity worldwide. The present case–control study aims to detect miRNAs differentially expressed in the first trimester maternal plasma with the view to identify predictive biomarkers for sPTD, between 320/7 and 366/7 weeks, that will allow for timely interventions for this serious pregnancy complication. Small RNA sequencing (small RNA-seq) of five samples from women with a subsequent sPTD and their matched controls revealed significant down-regulation of miR-23b-5p and miR-125a-3p in sPTD cases compared to controls, whereas miR-4732-5p was significantly overexpressed. Results were confirmed by qRT-PCR in an independent cohort of 29 sPTD cases and 29 controls. Statistical analysis demonstrated that miR-125a is a promising early predictor for sPTL (AUC: 0.895; 95% CI: 0.814-0.972; p < 0.001), independent of the confounding factors tested, providing a useful basis for the development of a novel non-invasive predictive test to assist clinicians in estimating patient-specific risk.
... Beta et al. conducted a predictive model of preterm delivery with the biochemical markers of the 1 st trimester, maternal characteristics and obstetric history and conclude that preterm delivery could be detected with a rate of 20% in nulliparous women and 38% in women with a history of preterm delivery ≥ 16 weeks, with 10% false positives 25 . Spencer et al. conclude that low PAPP-A increases the risk of prematurity, but the same does not apply to βHCG. ...
Objective:
Positive Combined First Trimester Screening and by risk groups: 0-50, 51-100, 101-150, 151-200, 201-250, and normal karyotype relate with negative screening for adverse perinatal results.
Method:
Retrospective study of cases and controls in single pregnancies, with predictive analysis using multivariate logistic regression.
Results:
3,791 screenings were performed at our unit in 2012, with a screening/number of deliveries ratio of 89.9%. There is a greater likelihood of the newborn being underweight (AOR = 2.6, 95% CI 1.2 – 5.7), premature (OR = 2.2, 95% CI 1.03 – 4.5), admitted to the ICU (OR = 7.4, CI 95% 1.5 – 34.6) or admitted to the Neonates department (AOR = 8.1, 95% CI 1.7 – 37.7) in the case group.
Conclusion:
Combined first trimester screening is a predictive method for pregnant women with a higher risk of adverse perinatal outcomes.
... Other than different initial BP, the magnitude and velocity of the trough at midpregnancy also varies, resulting different BPV. However, numerous studies did not incorporate BPV as a predictor for preterm delivery.29,[32][33][34][35] BP is an easily measured and routinely collected information during pregnancy, future studies should examine the possibility of BPV as a risk factor for preterm delivery. ...
Women's blood pressure (BP) changes throughout pregnancy. The effect of BP trajectories on preterm delivery is not clear. The authors aim to evaluate the association between maternal BP trajectories during pregnancy and preterm delivery. The authors studied pregnant women included in the Born in Guangzhou Cohort Study in China between February 2012 and June 2016. Maternal BP was measured at antenatal visits between 13 and 40 gestational weeks, and gestational age of delivery data was collected. The authors used linear mixed models to capture the BP trajectories of women with term, and spontaneous and iatrogenic preterm delivery. BP trajectories of women with various gestational lengths (34, 35, 36, 37, 38, 39, 40 weeks) were compared. Of the 17 426 women included in the analysis, 618 (3.55%) had spontaneous preterm delivery; 158 (.91%) had iatrogenic preterm delivery; and 16 650 (95.55%) women delivered at term. The BP trajectories were all J‐shaped curves for different delivery types. Women with iatrogenic preterm delivery had the highest mean BP from 13 weeks till delivery, followed by those with spontaneous preterm delivery and term delivery (p < .001). Trajectory analysis stratified by maternal parity showed similar results for nulliparous and multiparous women. Excluding women with pre‐eclampsia and gestational hypertension (GH) significantly attenuated the aforementioned association. Also, women with shorter gestational length tend to have higher BP trajectories during pregnancy. In conclusion, Women with spontaneous preterm delivery have a higher BP from 13 weeks till delivery than women with term delivery, while women with iatrogenic preterm delivery have the highest BP.
... The models performed better in parous than in nulliparous women 27 . Signs of uteroplacental dysfunction, such as low PAPP-A and increased UtA-PI, in women who delivered preterm for iatrogenic or spontaneous reasons, have been reported in previous studies 15,16,28 . These factors may help improve prediction for women at risk of iPTB and sPTB, regardless of parity. ...
Objectives:
Preterm birth (PTB) is a major public health problem worldwide. It can occur spontaneously or be medically indicated for obstetric complications, such as pre-eclampsia (PE) or fetal growth restriction. The main objective of the study was to investigate the implication of uteroplacental dysfunction in the first trimester in subsequent PTB.
Methods:
This retrospective cohort study on singleton pregnancies was conducted between March 2018 and December 2020. A total of 11,437 women underwent first-trimester screening for preterm PE using the Fetal Medicine Foundation algorithm, which includes maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and pregnancy-associated plasma protein (PAPP-A). Women with a risk of ≥1 in 50 for preterm PE were classified as high-risk and offered prophylactic aspirin 150mg and serial ultrasound assessments. The following outcomes at delivery were collected: PTB, iatrogenic PTB (iPTB) and spontaneous PTB (sPTB).
Results:
475 (4.2%) women had preterm births with 308 (64.8%) sPTB and 167 (35.2%) iPTB. Patients with PTB had a higher body mass index, were more likely to be Black or Asian and have a history of previous PTB. They also had higher MAP (87.70 vs 86.00, p<0.0001), higher UtA-PI MoM (0.99 vs 0.92, p<0.0001), lower PAPPA MoM (0.89 vs 1.08, p<0.0001). In women at high risk of PE, the odds ratio (OR) for iPTB was 6.0 (95% CI 4.29-8.43, p<0.0001) and for sPTB was 2.0 (95% CI 1.46-2.86, p<0.0001). A prediction model for PTB developed from this cohort performed as well as an existing first-trimester prediction model.
Conclusions:
Increased first-trimester risk for uteroplacental dysfunction was associated with both iatrogenic and spontaneous PTB, implying a shared aetiological pathway. The same factors used to predict PE risk show acceptable discrimination to predict PTB before 33 weeks. Women at high risk of uteroplacental dysfunction may warrant additional monitoring and management for an increased risk of spontaneous PTB. This article is protected by copyright. All rights reserved.
... The risk for spontaneous early preterm delivery is influenced by various maternal characteristics: it increases with maternal age, decreases with height, it is higher in women of African and South Asian racial origin, in cigarette smokers and in those conceiving after the use of ovulation induction drugs. An important predictor of preterm delivery is also the outcome of previous pregnancies; the risk is inversely related to gestation at previous spontaneous delivery, decreasing from 7% if the gestation was 16-24 weeks to 3% if 31-33 weeks, and to 0.6% if all deliveries were at term [14]. Screening in the first trimester, at 11-13 weeks by an algorithm combining maternal characteristics and obstetric history identified 38% of pregnancies resulting in spontaneous delivery before 34 weeks and 20% of those delivering at 34-36 weeks, at a false positive rate of 10% [15]. ...
There is consistent evidence that many of the pregnancy complications that occur late in the second and third trimester can be predicted from an integrated 11-13 weeks visit, where a maternal and fetal assessment are comprehensively performed. The traditional aims of the 11-13 weeks visit have been: establishing fetal viability, chorionicity and dating of the pregnancy, and performing the combined screening test for common chromosomal abnormalities. Recent studies have shown that the first trimester provides important information that may help to predict pregnancy complications, such as preeclampsia and fetal growth restriction, stillbirth, preterm birth, gestational diabetes mellitus and placenta accreta spectrum disorder. The aim of this manuscript is to review the methods available to identify pregnancies at risk for adverse outcomes after screening at 11-13 weeks. Effective screening in the first trimester improves pregnancy outcomes by allowing specific interventions such as administering aspirin and directing patients to specialist clinics for regular monitoring.
... 8,27,28 The biochemical tests are for pregnancy-associated plasma protein-A (PAPP-A) and placenta growth factor (PLGF). 29 In the fifth place is a group of screening tests, namely screen for foetal growth restriction (FGR), preeclampsia (PET), preterm labour (PTL), and placenta accrete spectrum. [9][10][11][12][13][14][15][16][17] Furthermore, to achieve optimal results from routine ultrasound examinations it is suggested that scans should be performed by individuals who fulfil the following criteria: have completed training in the use of diagnostic ultrasonography and related safety issues, participate in continuing medical education activities, have established appropriate care pathways for suspicious or abnormal findings and participate in established quality assurance programs. 30 Generally, it is not known to what extent the first obstetric ultrasound in Nigeria complies with international norm in terms of the content of the scans, conduct of the scans, timing, engagement of the Sonographers in continuous professional development, the biometric parameters measured and the report given to patients. ...
Background: The study was prompted by the heterogeneity in the content and the performance of dating or first obstetric ultrasound) scans in Nigeria. The primary aim of the study therefore was to determine whether the conduct of the scans conform to international norms. The secondary goal was to access the implications of the scans for maternal and foetal care. Methods: The study was of mixed design-observational, cross-sectional with audit component, carried out at the Rivers State university teaching hospital (RSUTH), Nigeria from November, 2020 to February 2021. A literature search was carried out on the subject and standards were deduced from the review. 417 consecutive patients were recruited from the antenatal clinic and data on their history and the conduct of the scans were collected. The content of individual scan report was compared with international norms. Data were analysed using Epi. Info 2018 software. Results: There were no guidelines nor uniformity in the conduct of dating or first obstetric ultrasound scans at the RSUTH. Out of the total 408 scan reports, 108 (26.47%) and 300 (73.53) took place inside and outside the RSUTH respectively. The gestational ages at the scans ranged from 8 to 41 weeks. Appropriate biometric parameters were used in 115 (28.19%) reports while in the rest, inappropriate or incomplete parameters were used. Furthermore, the following were not on the menu for the first obstetric scans: determination of chorionicity/amnionicity in multiple pregnancies, anomaly scan, screening for chromosomal abnormalities, foetal growth restriction (FGR), preeclampsia, preterm labour and for morbid adherence of the placenta. The deficiencies in the first obstetric ultrasound would likely lead to wrong dating and inaccurate growth assessment with associated adverse maternal and foetal outcomes, including wrong timing for obstetric interventions and also increased prevalence of those conditions that were not screened for. Conclusions: Absence of guidelines, inaccurate dating and foetal growth assessment and non-performance of important obstetric screening procedures were likely to lead to adverse maternal foetal outcomes. There was therefore urgent need to formulate national guidelines on the subject, adopt effective referral cascade for scans and to introduce practical approach to training in maternal foetal medicine in tertiary institutions in Nigeria.
... 8 According to American Pregnancy Association, women are at greatest risk of preterm labor and subsequent delivery in her future pregnancies if they had previous premature birth or second trimester abortion, history of infertility (primary/secondary) or pregnant with multiples. 9 Women with history of vaginal bleed or subnormal amount of liquor (either polyhydramnios or oligohydramnios) or with fetal mal-presentation are at higher risk of suffering from premature labour and birth of baby, before 37 completed weeks of gestation. 10 Maternal infections like urinary tract infection or bacterial vaginosis are strong risk factors in the chain of causation of preterm births. ...
Background: Pakistan has one of the highest rates of preterm births, nearly 16 for every 100 babies born. Around 4% of these premature babies, are at highest likelihood of death. The objective of this study was to assess association of multiple risk factors with preterm birth in Pakistani women. Patients and methods: An analytical cross-sectional study was carried out in Obstetrics and Gynecology Department of Akhtar Saeed Trust Hospital and Farooq Hospital, West Wood Branch, Lahore from October 2018 to December 2019. Total 116 pregnant females who gave birth to preterm babies with gestational age between 20-37 weeks were included. Data about patients socio-demographic profile, previous obstetric history and current gestational profile was collected using closed ended structured questionnaire. Variables were presented in the form of frequency tables. Chi-square and Fisher exact test were applied to establish association of various risk factors and preterm presentation of patient p-was taken as significant. Results: Out of 116 participants, 49 (42.2%) were aged between 20-25 years, 47 (40.5%) were illiterate. Of the total sample 60 (51.7 %) participants were obese (BMI >30). Eighty-two (70.7%) patients were multigravida and 65 (56.1%) gave the history of previous cesarean section. Significant association was found between preterm birth and multi-parity (p=0.001), previous history of abortion (p=0.000), intrauterine death (p=0.001), infertility (p=0.04), cesarean-section (p=0.000), and inter-pregnancy interval of less than 24 months (p=0.007). Other significant factors associated with preterm labour were urinary tract infections (p=0.001), documented fever more than 101 o F (p=0.000), anemia (p=0.000), singleton pregnancy (p=0.000) and cephalic fetal presentation (p=0.002), during current pregnancy. Conclusion: Multi-gravidity, history of abortion, intrauterine death, previous infertility, cesarean-section, inter-pregnancy interval of less than 24 months, UTI, genital tract infection, anemia, singleton pregnancy and cephalic fetal presentation during current pregnancy were observed to be significantly associated with preterm births.
... El futuro de la Obstetricia y en particular de la Medicina Fetal está en la predicción de los eventos obstétricos, tal como lo demostráramos recientemente para parto pretérmino (23) . Por lo que nuestros hallazgos son de trascendental importancia por cuanto, a diferencia de los estudios en otros países, nuestras gestantes constituyen población no seleccionada sin tamizaje de cromosomopatías, donde el hallazgo ecográfico del fémur corto en el segundo trimestre no asociado a otra patología y con crecimiento normal al momento del examen ecográfico constituye un predictor de restricción de crecimiento intrauterino. ...
Antecedentes: El hallazgo ecográfico de fémur corto (longitud menor del percentil 5) en la valoración ecográfica rutinaria del feto del segundo trimestre plantea un desafío diagnóstico y de manejo. Clásicamente ha sido asociado a cromosomopatías y displasia esquelética. Existen pocos reportes que valoran los resultados perinatales de los fetos con fémur corto en el examen del segundo trimestre. Objetivos: Determinar la asociación de fetos con fémur corto aislado en fetos del segundo trimestre y recién nacidos con restricción del crecimiento intrauterino (RCIU) y su asociación con otros resultados perinatales adversos. Diseño: Estudio de cohorte retrospectivo. Institución: Unidad de Medicina Fetal, Instituto Nacional Materno Perinatal, Lima, Perú. Participantes: Gestantes de 16 a 28 semanas. Intervenciones: Para cumplir con el tamaño muestral, se seleccionó los fetos evaluados durante el periodo de tres años (2006 a 2008) que cumplieron los criterios de inclusión. Se clasificó los fetos de 278 gestantes de 16 a 28 semanas en dos grupos: 89 con longitud de fémur corto aislado como único hallazgo, sin RCIU al momento de la evaluación (casos), y 189 fetos con longitud de fémur normal (controles). Se excluyó las gestantes cuyos fetos tenían anormalidades cromosómicas o estructurales y aquellas gestaciones con embarazos múltiples. Se realizó un análisis univariado mostrando porcentajes y medidas de tendencia central y un análisis bivariado con la prueba t, para las variables continuas, y la prueba exacta de Fisher, para las variables categóricas. Principales medidas de resultados: Asociación del fémur corto fetal con complicaciones fetales y maternas. Resultados: El grupo de fetos con fémur corto aislado tuvo recién nacidos con peso promedio significativamente menor que las gestantes de fetos con longitud de fémur normal, con una diferencia estadística y clínicamente significativa de 412,3 g (P=0,000), encontrándose un mayor porcentaje de recién nacidos con RCIU en 14,6% versus 6,8% en el grupo control (p=0,000). Calculamos un OR de 2,32 (IC95%:1,03 a 5,23) para RCIU. Además, se observó que las gestantes con fetos de fémur corto aislado desarrollaron hipertensión gestacional (11,2% versus 4,8%, p=0,046) y preeclampsia (11,2% versus 2,1%, p=0,001). Asimismo, hubo mayor número de casos con puntaje de Ápgar <7 a los 5 minutos en el grupo de fetos con fémur corto (4,5% versus 0,5%, p=0,02). Igualmente, hubo dos casos de muerte perinatal en el grupo de fetos con fémur corto aislado. Conclusiones: El fémur corto, como hallazgo ecográfico aislado en fetos del segundo trimestre, está asociado a recién nacidos con RCIU y con gestaciones complicadas con hipertensión gestacional o preeclampsia. Este es la cohorte más grande publicada hasta el momento de fetos con fémur corto aislado.
... Effective screening for PTB can be achieved by combining maternal history, demographic characteristics [4], and cervical length (CL) on the second-trimester scan [5]. The most efficient isolated marker for PTB is the CL in a transvaginal ultrasound (TVS) performed between 20 and 24 weeks [6,7]. ...
Background:
Several studies were published about cervical pessary, with controversial results. These studies demonstrated that the patient follow-up after pessary insertion is very different between the study centers and the number of pessary insertions per center was often <30 cases. This study aims to determine cervical pessary performance in singleton pregnancies with a short cervix based on a single center learning curve.
Methods:
Between 2011 and 2018, 128 singleton pregnancies between 18 and 24 gestational weeks with a short cervix (<25 mm) were referred to our clinic. All cases were treated with progesterone, and when available in our supplies (due to low resources) cervical pessary was also offered. Three groups were created for statistical analysis: Group 1 (n = 33), treated with progesterone-only; Groups 2 and 3, treated with cervical pessary plus progesterone. Group 2 included the first cases (n = 30) of pessary, defined by a learning curve and cumulative sum analysis, while Group 3 included the subsequent 65 cases. The primary outcome was preterm birth (PTB) < 34 gestational weeks.
Results:
The learning curve was performed with all cases of pessary plus progesterone, and 30 patients were obtained as the number needed for learning, in our study with two operators. The PTB rate < 34 weeks was 27.3, 20, and 4.6% in groups 1, 2, and 3, respectively. There was no significant difference between Group 1 and 2 (OR 1.1; 95% CI 0.066 - 18.45; p = .945). When comparing Groups 1 and 3 there was a significant difference in PTB rates (OR 0.08; CI95% 0.01-0.42; p = .003). Considering Kaplan-Meyer Survival analysis, we can observe that the performance of progesterone alone (Group 1) was similar to Group 2 (progesterone + first 30 cases of pessary) (p = .432), but the performance of Group 3 (progesterone + subsequent 65 cases of pessary) and Group 1 shows a statistically significant difference (p = .011).
Conclusion:
Learning curve and cumulative sum analysis determined that the application and surveillance of at least 30 patients is required to see significant improvements in the primary outcome of PTB < 34 weeks.
Preeclampsia and preterm birth are the main causes of perinatal and maternal morbidity and mortality. In addition to indicating intensified monitoring, early detection of women with an increased risk enables initiation of prophylactic measures. Preeclampsia screening should ideally be carried out in the first trimester using a combination of different markers, as this has the best predictive value for an early complication, therefore allowing the only effective prophylaxis—low-dose aspirin—to be initiated in good time. Individual markers (especially anamnestic factors) do not achieve these predictive values. In the further course of pregnancy, a prediction of hypertensive pregnancy complications can be achieved in the second and third trimester by using the multimarker algorithm. In contrast to preeclampsia screening, there is currently no multifactorial algorithm available for screening or predicting premature birth. The most important parameters are maternal obstetric history and the measurement of cervical length in the second trimester.
Background
First, a logistic regression model, based on maternal demographic characteristics and medical history and blood pressure at 11‐13 weeks’ gestation, can identify about 70% of women who develop future chronic hypertension (CH) in the three years following pregnancy, at screen positive rate of 10%. Second, at mid‐gestation women who subsequently develop hypertensive disorders of pregnancy (HDP) have increased peripheral vascular resistance and mild cardiac functional and morphological alterations and these cardiovascular abnormalities persist for at least 2 years after delivery.
Objective
To examine whether the use of the first‐trimester risk for subsequent development of CH can help to identify women at high risk for cardiovascular maladaptation at mid‐gestation.
Methods
Prospective observational study in 3812 women with singleton pregnancies women attending for a routine hospital visit at 11+0 to 13+6 weeks’ gestation and again at 19+1 to 23+3 weeks at King's College Hospital, London, UK between August 2019 and August 2020. The first‐trimester visit included recording of maternal demographic characteristics and medical history and measurement of systolic and diastolic blood pressure. At mid‐gestation detailed maternal cardiovascular assessment was carried out. The association of risk for development of CH, determined from first‐trimester assessment, and cardiovascular indices at mid‐gestation was examined.
Results
Women who are at high‐risk for development of future CH, compared to those at low‐risk, had a higher incidence of hypertensive disorders of pregnancy (HDP). In addition, high‐risk women, had reduced systolic and diastolic function at mid‐gestation. Among women with HDP, those who were high‐risk for future CH, compared to those at low‐risk, also had worse cardiac function at mid‐gestation.
Conclusion
Use of a model for first‐trimester prediction of subsequent development of CH can identify women who show evidence of cardiac maladaptation at mid‐gestation. Further studies are needed to clarify whether women who screen as high‐risk for future CH, compared to those at low‐risk, have reduced cardiac function beyond pregnancy.
This article is protected by copyright. All rights reserved.
Objectives
The aim of this study was to evaluate the relationship between the cervix and the threat of preterm labor in singleton pregnancies between gestational weeks less than 37 and greater than 37 weeks in correlation with utero‐cervical angle (UCA) and cervical length (CL) measurements.
Materials and Methods
We conducted a prospective cohort study with UCA and CL measurements in patients with threatened preterm labor (TPL). Primary outcome was differences in UCA and CL measurements in relationship to maternal characteristics and perinatal outcome between groups. Secondary outcome evaluated measurement results and influencing factors for delivery within 7 days, between 1 and 4 weeks and beyond 4 weeks.
Results
Overall 152 patients were divided into as study/preterm group (<37 weeks; n = 56) and the control/term group (≥37 weeks; n = 96). Mean gestational age at admission was similar in both groups (30.98 ± 2.83 vs. 30.36 ± 2.63 weeks, p = 0.149) with similar CL (33.9 ± 6.34 vs. 32.02 ± 8.88 mm, p = 0.132), but wider UCA in the preterm group (81.65 ± 16.81° vs. 99.21 ± 22.33°, p < 0.001). Multivariate logistic regression analysis for preterm delivery was significant for nulliparity and UCA measurement. The factor for delivering before 37 gestational weeks within 7 days was the gestational week at admission ( p = 0.046). UCA and CL measurements were statistically significant for distinguishing patients for delivery within 7 days and beyond 4 weeks ( p = 0.001 for CL and p = 0.0001 for UCA). NPV was found 92.5, 92.2, and 92.3 for UCA >105°, CL ≤30 mm, and Bishop score >3, respectively.
Conclusion
Combined measurement of TV UCA and CL represents stronger predictors for sPTB ultrasonographically, demonstrating the uterocervical sub‐segment maturation before the active onset of labor.
Objective:
To evaluate the association between hCG and adverse pregnancy outcomes.
Data sources:
Medline, Embase, PubMed and Cochrane were searched in November 2021 using medical subject headings (MeSH) and relevant keywords.
Study eligibility criteria:
Published full text studies of pregnant women with serum hCG testing between 8-28 week gestation investigating fetal outcomes (fetal death in-utero, small for gestational age, preterm birth) or maternal factors (hypertension in pregnancy: preeclampsia, pregnancy induced hypertension, placental abruption, HELLP syndrome, gestational diabetes).
Study appraisal and synthesis methods:
Studies were extracted using RedCap software. Newcastle Ottawa Scale was used to assess for risk of bias. Final meta-analyses underwent further quality assessment using grading of recommendations, assessment, development, and evaluations (GRADE) method.
Results:
185 studies were included in the final review including the outcomes fetal death in-utero (45), small for gestational age (79), preterm delivery (61), hypertension in pregnancy (107), gestational diabetes (29), placental abruption (16), and haemolysis, elevated liver enzymes and low platelets syndrome (HELLP) (2). Data were analysed separately based on categorical measurement of hCG and hCG measured on a continuous scale. Eligible studies underwent meta-analysis to generate a pooled OR (categorical hCG level) or difference in medians (hCG continuous scale) between outcome groups. First trimester low hCG levels were associated with preeclampsia and fetal death in-utero, whereas high hCG levels were associated with preeclampsia. Second trimester high hCG levels were associated with fetal death in-utero and preeclampsia.
Conclusions:
hCG levels are associated with placenta mediated adverse pregnancy outcomes. Both high and low hCG levels in the first trimester of pregnancy can be early warning signs of adverse outcomes. Further analysis of hCG subtypes and pregnancy outcomes is required to determine the diagnostic utility of these findings in reference to specific cut-off values.
Introduction: Nowadays, the risk stratification of preterm birth (PTB) and its prediction remain a challenge. Many risk factors associated with PTB have been identified, and risk scoring systems (RSSs) have been developed to face this challenge. The objectives of this systematic review were to identify RSSs for PTB, the variables they consist of, and their performance. Materials and methods: Two databases were searched, and two authors independently performed the screening and eligibility phases. Records studying an RSS, based on specified variables, with an evaluation of the predictive value for PTB, were considered eligible. Reference lists of eligible studies and review articles were also searched. Data from the included studies were extracted. Results: A total of 56 studies were included in this review. The most frequently incorporated variables in the RSS included in this review were maternal age, weight, history of smoking, history of previous PTB, and cervical length. The performance measures varied widely among the studies, with sensitivity ranging between 4.2% and 92.0% and area under the curve (AUC) between 0.59 and 0.95. Conclusions: Despite the recent technological and scientifical evolution with a better understanding of variables related to PTB and the definition of new ultrasonographic parameters and biomarkers associated with PTB, the RSS’s ability to predict PTB remains poor in most situations, thus compromising the integration of a single RSS in clinical practice. The development of new RSSs, the identification of new variables associated with PTB, and the elaboration of a large reference dataset might be a step forward to tackle the problem of PTB.
Objectives:
One in five mothers will experience perinatal depression (PND) during pregnancy and within their first year following childbirth. Current evidence suggests the short-term efficacy of Mindfulness-based interventions (MBI) for perinatal women, but the extent to which this positive impact remains the early postpartum period is unclear. This study investigated the short- and maintenance efficacy of a mobile-delivered four-immeasurable MBI on PND, and obstetric and neonatal outcomes.
Methods:
Seventy-five adult pregnant women suffering from heightened distress were randomized to receive a mobile-delivered four-immeasurable MBI (n = 38) or a web-based perinatal education program (n = 37). PND was measured by Edinburgh Postnatal Depression Scale at baseline, post-intervention, 37th-week gestation, and 4-6 weeks postpartum. Outcomes also included obstetric and neonatal outcomes, trait mindfulness, self-compassion, and positive affect.
Results:
Participants reported an average age of 30.6 (SD = 3.1) years with a mean gestational age of 18.8 (SD = 4.6) weeks. In intention-to-treat analyses, women in the mindfulness group showed a significantly greater reduction in depression from baseline to post-intervention (adjusted mean change difference [β] = -3.9; 95%CI = [-6.05, -1.81]; d = -0.6), and the reduction sustained until 4-6 weeks postpartum (β = -6.3; 95%CI = [-8.43, -4.12]; d = -1.0), compared with control. They had a significantly reduced risk of emergent cesarean section (relative risk = 0.5) and gave birth to infants with higher Apgar scores (β = 0.6;p = .03; d = 0.7). Depression reduction before giving birth significantly mediated the intervention effect on lowering the emergency cesarean risk.
Conclusions:
With a reasonably low dropout rate (13.2 %), the mobile-delivered MBI can be an acceptable and effective intervention for reducing depression throughout pregnancy and postpartum. Our study also suggests the potential benefits of early prevention for mitigating emergent cesarean section risk and enhancing neonatal health.
Objective To develop and validate a risk prediction
model for the prediction of preterm birth using maternal
characteristics.
Design This was a retrospective follow-up study. Data
were coded and entered into EpiData, V.3.02, and were
analysed using R statistical programming language
V.4.0.4 for further processing and analysis. Bivariable
logistic regression was used to identify the relationship
between each predictor and preterm birth. Variables with
p≤0.25 from the bivariable analysis were entered into
a backward stepwise multivariable logistic regression
model, and significant variables (p<0.05) were retained
in the multivariable model. Model accuracy and goodness
of fit were assessed by computing the area under the
receiver operating characteristic curve (discrimination) and
calibration plot (calibration), respectively.
Setting and participants This retrospective study was
conducted among 1260 pregnant women who did prenatal
care and finally delivered at Felege Hiwot Comprehensive
Specialised Hospital, Bahir Dar city, north-west Ethiopia,
from 30 January 2019 to 30 January 2021.
Results Residence, gravidity, haemoglobin <11mg/dL,
early rupture of membranes, antepartum haemorrhage
and pregnancy-induced hypertension remained in the final
multivariable prediction model. The area under the curve of
the model was 0.816 (95% CI 0.779 to 0.856).
Conclusion This study showed the possibility of
predicting preterm birth using maternal characteristics
during pregnancy. Thus, use of this model could help
identify pregnant women at a higher risk of having a
preterm birth to be linked to a centre.
Biomarkers in Medicine is a comprehensive guide to understanding the current and future status of biomarkers. The book features 27 chapters focusing on disease biomarkers for diseases such as cancer, neurodegenerative diseases, cardiac diseases, metabolic conditions and much more.
This book supplies readers with the unique insight of experts in multiple specialties in medicine and life sciences who have extensive experience in diagnostics and clinical laboratories. The book includes case studies and practical examples from different classes of biomarkers on different platforms, including new data for biomarkers in different therapeutic indications. In addition to presenting biomarker information, each chapter covers the relevant pathology and also emphasizes on preclinical and clinical manifestation of the disease process.
Clinicians managing patients or clinical trials, clinical researchers, clinical laboratories, diagnostic companies, regulatory agencies, medical school graduate students, academic students, and the general public involved in healthcare delivery will all benefit from information presented in this book.
Abstract Preterm birth, the leading cause of perinatal morbidity and mortality, is associated with increased risk of short- and long-term adverse outcomes. For women identified as at risk for preterm birth attributable to a sonographic short cervix, the determination of imminent delivery is crucial for patient management. The current study aimed to identify amniotic fluid (AF) proteins that could predict imminent delivery in asymptomatic patients with a short cervix. This retrospective cohort study included women enrolled between May 2002 and September 2015 who were diagnosed with a sonographic short cervix (
The use of the second trimester alpha-fetoprotein (AFP) along with the first trimester pregnancy-associated plasma protein-A (PAPP-A) has been found to be useful in the estimation of unfavourable pregnancy outcome. Our aim in this study was to determine the relationship between maternal PAPP-A and b-hCG and AFP concentrations in spontaneous preterm birth (sPTB). This prospective cohort study included 372 singleton pregnancies with PAPP-A, b-hCG and AFP levels in the first trimester, which were converted to multiples of the median (MoM). The predictive ability of AFP-to-PAPP-A and AFP-to-b-hCG ratios for sPTB was evaluated. The risk for sPTB ≤34 weeks increased in women with AFP-to-PAPP-A ratio >7 (OR 2.9, 95% CI 1.2–6.4). Women with AFP-to-b-hCG ratio >0.6 had a 3.5-fold higher risk for sPTB ≤32 weeks. Increased maternal AFP-to-PAPP-A or AFP-to-b-hCG ratios in the first trimester may help to predict pregnant women at high risk for sPTB, and this may be beneficial in developing management plans.
• Impact Statement
• What is already known on this subject? There is a synergistic association between the combination of low pregnancy-associated plasma protein-A (PAPP-A) in the first trimester with alpha-fetoprotein (AFP) in the second trimester with subsequent development of PTB. Maternal serum biochemical markers measured as a part of aneuploidy screening are reflective of pregnancy adverse outcomes related with placental insufficiency. PAPP-A and AFP have a low predictive ability to determine women at high risk for preterm birth.
• What do the results of this study add? Elevated AFP:PAPP-A or AFP:B-HCG ratio in the first trimester is associated with increased risk for sPTB. The ratios of these biochemical markers in the first trimester may be beneficial to identify women at high risk for sPTB.
• What are the implications of these findings for clinical practice and/or further research? The ratios may predict pregnant women at high risk for sPTB, and such risk may be helpful in the development of a management plan. Incorporation of AFP:PAPP-A or AFP:B-HCG ratios in the first trimester may help to improve the screening efficacies, and provide a simple alternative tool.
Objectives:
To determine whether first trimester biomarkers of placental function can be used to screen for spontaneous preterm birth (sPTB) and develop prediction models with maternal factors, obstetric history and biomarkers of placental function at 11-13 weeks for the calculation of patient-specific risks for sPTB.
Methods:
This was a retrospective secondary analysis of the data derived from a prospective cohort study for first trimester screening for preeclampsia in singleton pregnancies at 11-13+6 weeks' gestation in women attending for routine Down syndrome screening at a tertiary obstetric unit between December 2016 to September 2019. A split-sample internal validation method was adopted to explore and develop prediction models for all sPTB at <37 weeks and those with preterm prelabor rupture of membranes (PPROM) using maternal risk factors, uterine artery Doppler indices, serum placental growth factor (PlGF), pregnancy associated plasma protein-A (PAPP-A), and beta human chorionic gonadotropin (β-hCG). Screening performance was assessed by receiver operating characteristic (ROC) curve analysis with the areas under the ROC curves (AUC) calculated.
Results:
A total of 9,298 singleton pregnancies were included in this study. Spontaneous preterm delivery at <37 weeks and <34 weeks occurred in 362 cases (3.89%) including 231 cases (2.48%) of PPROM, and 87 cases (0.94%) including 39 cases (0.42%) of PPROM, respectively. Identified maternal risk factors for sPTB at <37 weeks included chronic hypertension, conception by in-vitro fertilization and history of prior PTB; whereas for PPROM at <37 weeks included conception by in-vitro fertilization and history of prior PTB. The median PlGF multiple of median (MoM) and PAPP-A MoM were significantly reduced in women who had sPTB at <37 weeks as well as in those who had PPROM, compared to those who delivered at term. Screening with a combination of maternal risk factors and PAPP-A/PlGF achieved better performance in predicting sPTB at <37 weeks (AUC 0.630 vs 0.555, detection rate (DR) 24.8% vs 16.6% at false positive rate (FPR) of 10%, p=<0.0001) and PPROM at <37 weeks (AUC 0.643 vs 0.558, DR 28.1% vs 17.0% at FPR of 10%, p=<0.0001) than using maternal risk factors alone. Both models were successfully applied to the internal validation dataset, with AUC of 0.628 and 0.650, respectively.
Conclusions:
We have demonstrated that low levels of maternal serum PAPP-A and PlGF in the first trimester are associated with increased risks of sPTB and PPROM. However, further research is needed to identify additional biomarkers to improve the screening performance of the combined model using maternal risk factors and PAPP-A/PlGF before clinical application. This article is protected by copyright. All rights reserved.
This authoritative textbook provides a much-needed guide for postgraduate trainees preparing for the European Board and College of Obstetrics and Gynaecology (EBCOG) Fellowship examination. Published in association with EBCOG, it fully addresses the competencies defined by the EBCOG curriculum and builds the clinical practice related to these competencies upon the basic science foundations. Volume 1 covers the depth and breadth of obstetrics, and draws on the specialist knowledge of four highly experienced Editors and over 100 contributors from across Europe, reflecting the high-quality training needed to ensure the safety and quality of healthcare for women and their babies. It incorporates key international guidelines throughout, along with colour diagrams and photographs for easy understanding. This is an invaluable resource, not only for postgraduate trainees planning to sit the EFOG examination, but also for practising specialists looking to update their knowledge and skills to meet the ever-evolving complexity of clinical practice.
Introduction: To determine the impact on preterm birth (PTB) of a history of large
loop excision of the transformation zone (LLETZ)-alone compared with a history of
previous preterm birth-alone (PPTB) or a history of both (LLETZ+PPTB). Secondary
analyses were performed to evaluate the impact of antenatal interventions, depth of
cervical excision, and patient risk factors on PTB rate in each cohort.
Material and methods: A retrospective observational cohort study of women referred
to a tertiary Antenatal Prematurity Prevention Clinic with a history of LLETZ, PPTB,
or LLETZ+PPTB. Information was collated from routinely collected clinical data on
patient demographics, previous obstetric history, LLETZ dimensions, antenatal inves�tigations/interventions, and gestation at delivery.
Results: A total of 1231 women with singleton pregnancies were included, 543 with
history of LLETZ-alone, 607 with a history of PPTB-alone and 81 with a history of
LLETZ+PPTB. PTB rates were 8.8% in the LLETZ-alone group, which mirrored the PTB
rate in the local background obstetric population (8.9%) compared with 28.7% in the
PPTB-alone and 37.0% in the LLETZ+PPTB cohorts. PTB rates were higher in LLETZ
cohorts treated with antenatal intervention (cervical cerclage or progesterone pessary)
and there was no evidence of an effect of intervention on risk of PTB in post-excision
patients with identified shortened mid-trimester cervical length. Logistic regression
modeling identified PPTB as a strong predictor of recurrent PTB. Excision depth was
correlated with gestation at delivery in the LLETZ-alone group (r = −0.183, p < 0.01)
although this only reached statistical significance at depths of 20 mm or more (odds
ratio [OR] 3.40, 95% CI 1.04–1.11, p = 0.04). Depth of excision was not correlated with
delivery gestation in the LLETZ+PPTB group (r = −0.031, p = 0.82).
Conclusions: PPTB has a greater impact on subsequent PTB risk compared with depth
of cervical excisional treatment. The value and nature of antenatal interventions
should be investigated in the post-excision population.
Resumen
Muchos estudios han documentado la asociación entre valores bajos de PAPP-A y β-hCG en el suero materno durante el primer trimestre, así como efectos materno-fetales adversos.
Para valorar dicha relación, en nuestro medio se llevó a cabo un análisis retrospectivo de casos y controles anidado en una cohorte de pacientes con embarazo único en quienes se realizó el cribado del primer trimestre entre 2017 y 2018. Se consideraron casos aquellas pacientes con niveles de MoM PAPP-A y/o β-hCG iguales o inferiores al percentil 5, y como controles a una muestra aleatorizada de pacientes con niveles séricos por encima de dicho percentil.
El análisis de nuestros resultados demostró que en los grupos con niveles bajos de MoM PAPP-A y MoM β-hCG se observó un mayor riesgo de desarrollar crecimiento intrauterino restringido que en el grupo control (OR: 2,7 y 3,17, respectivamente). En el grupo MoM PAPP-A ≤ p5 también se obtuvo un riesgo 3,8 veces superior de estados hipertensivos del embarazo (IC: 1,94-7,83) y 7,9 veces mayor de muerte fetal anteparto (IC:1,09-217,4). Estas dos variables no resultaron estadísticamente significativas en el grupo MoM β-hCG ≤ p5.
Nuestros hallazgos confirmaron que los niveles bajos de PAPP-A y β-hCG en el suero de las gestantes se asoció con un riesgo elevado de desarrollar complicaciones obstétricas, por lo que podrían utilizarse para la detección precoz de las mismas y prevención de malos resultados obstétricos.
Background
Early antenatal care (ANC) reduces maternal and neonatal morbidity and mortality through identification of pregnancy-related complications, yet 44% of Rwandan women present to ANC after 16 weeks gestational age (GA). The objective of this study was to identify factors associated with delayed initiation of ANC and describe differences in the obstetric risks identified at the first ANC visit (ANC-1) between women presenting early and late to care.
Methods
This secondary data analysis included 10,231 women presenting for ANC-1 across 18 health centers in Rwanda (May 2017-December 2018). Multivariable logistic regression models were constructed using backwards elimination to identify predictors of presentation to ANC at ≥16 and ≥24 weeks GA. Logistic regression was used to examine differences in obstetric risk factors identified at ANC-1 between women presenting before and after 16- and 24-weeks GA.
Results
Sixty-one percent of women presented to ANC at ≥16 weeks and 24.7% at ≥24 weeks GA, with a mean (SD) GA at presentation of 18.9 (6.9) weeks. Younger age (16 weeks: OR = 1.36, 95% CI: 1.06, 1.75; 24 weeks: OR = 1.33, 95% CI: 0.95, 1.85), higher parity (16 weeks: 1–4 births, OR = 1.55, 95% CI: 1.39, 1.72; five or more births, OR = 2.57, 95% CI: 2.17, 3.04; 24 weeks: 1–4 births, OR = 1.93, 95% CI: 1.78, 2.09; five or more births, OR = 3.20, 95% CI: 2.66, 3.85), lower educational attainment (16 weeks: primary, OR = 0.75, 95% CI: 0.65, 0.86; secondary, OR = 0.60, 95% CI: 0.47,0.76; university, OR = 0.48, 95% CI: 0.33, 0.70; 24 weeks: primary, OR = 0.64, 95% CI: 0.53, 0.77; secondary, OR = 0.43, 95% CI: 0.29, 0.63; university, OR = 0.12, 95% CI: 0.04, 0.32) and contributing to household income (16 weeks: OR = 1.78, 95% CI: 1.40, 2.25; 24 weeks: OR = 1.91, 95% CI: 1.42, 2.55) were associated with delayed ANC-1 (≥16 and ≥24 weeks GA). History of a spontaneous abortion (16 weeks: OR = 0.74, 95% CI: 0.66, 0.84; 24 weeks: OR = 0.70, 95% CI: 0.58, 0.84), pregnancy testing (16 weeks: OR = 0.48, 95% CI: 0.33, 0.71; 24 weeks: OR = 0.41, 95% CI: 0.27, 0.61; 24 weeks) and residing in the same district (16 weeks: OR = 1.55, 95% CI: 1.08, 2.22; 24 weeks: OR = 1.73, 95% CI: 1.04, 2.87) or catchment area (16 weeks: OR = 1.53, 95% CI: 1.05, 2.23; 24 weeks: OR = 1.84, 95% CI: 1.28, 2.66; 24 weeks) as the health facility were protective against delayed ANC-1. Women with a prior preterm (OR, 0.71, 95% CI, 0.53, 0.95) or low birthweight delivery (OR, 0.72, 95% CI, 0.55, 0.95) were less likely to initiate ANC after 16 weeks. Women with no obstetric history were more likely to present after 16 weeks GA (OR, 1.18, 95% CI, 1.06, 1.32).
Conclusion
This study identified multiple predictors of delayed ANC-1. Focusing existing Community Health Worker outreach efforts on the populations at greatest risk of delaying care and expanding access to home pregnancy testing may improve early care attendance. While women presenting late to care were less likely to present without an identified obstetric risk factor, lower than expected rates were identified in the study population overall. Health centers may benefit from provider training and standardized screening protocols to improve identification of obstetric risk factors at ANC-1.
Background
Preterm labour, between 24 to 28 weeks of gestation, remains prevalent in low resource settings. There is evidence of improved survival after 24 weeks though the ideal mode of delivery remains unclear. There are no clear management protocols to guide patient management. We sought to determine the incidence of preterm labour occurring between 24 to 28 weeks, its associated risk factors and the preferred mode of delivery in a low resource setting with the aim of streamlining patient care.
Methods
Between February 2020 and September 2020, we prospectively followed 392 women with preterm labour between 24 to 28 weeks of gestation and their newborns from admission to discharge at Kawempe National Referral hospital in Kampala, Uganda. The primary outcome was perinatal mortality associated with the different modes of delivery. Secondary outcomes included neonatal and maternal infections, admission to the Neonatal Special Care Unit (SCU), need for neonatal resuscitation, preterm birth and maternal death. Chi-square test was used to assess the association between perinatal mortality and categorical variables such as parity, mode of delivery, employment status, age, antepartum hemorrhage, digital vaginal examination, and admission to Special Care unit. Multivariate logistic regression was used to assess the association between comparative outcomes of the different modes of delivery and maternal and neonatal risk factors.
Results
The incidence of preterm labour among women who delivered preterm babies between 24 to 28 weeks was 68.9% 95% CI 64.2–73.4). Preterm deliveries between 24 to 28 weeks contributed 20% of the all preterm deliveries and 2.5% of the total hospital deliveries. Preterm labour was independently associated with gravidity (p-value = 0.038), whether labour was medically induced (p-value <0.001), number of digital examinations (p-value <0.001), history of vaginal bleeding prior to onset of labour (p-value < 0.001), whether tocolytics were given (p-value < 0.001), whether an obstetric ultrasound scan was done (p-value <0.001 and number of babies carried (p-value < 0.001). At multivariate analysis; multiple pregnancy OR 15.45 (2.00–119.53), p-value < 0.001, presence of fever prior to admission OR 4.03 (95% CI .23–13.23), p-value = 0.002 and duration of drainage of liquor OR 0.16 (0.03–0.87), p-value = 0.034 were independently associated with preterm labour. The perinatal mortality rate in our study was 778 per 1000 live births. Of the 392 participants, 359 (91.5%), had vaginal delivery, 29 (7.3%) underwent Caesarean delivery and 4 (1%) had assisted vaginal delivery. Caesarean delivery was protective against perinatal mortality compared to vaginal delivery OR = 0.36, 95% CI 0.14–0.82, p-value = 0.017). The other protective factors included receiving antenatal corticosteroids OR = 0.57, 95% CI 0.33–0.98, p-value = 0.040, Doing 3–4 digital exams per day, OR = 0.41, 95% 0.18–0.91, p-value = 0.028) and hospital stay of > 7 days, p value = 0.001. Vaginal delivery was associated with maternal infections, postpartum hemorrhage, and admission to the Special Care Unit.
Conclusion
Caesarean delivery is the preferred mode of delivery for preterm deliveries between 24 to 28 weeks of gestation especially when labour is not established in low resource settings. It is associated with lesser adverse pregnancy outcomes when compared to vaginal delivery for remote gestation ages.
Aim: In this study, we aimed to compare the obstetric and neonatal outcomes and effects of subchorionichematoma (SH) in women with threatened abortion (TA) and healthy controls.Methods: The medical records of pregnant women were retrospectively reviewed. The obstetric and neonatal outcomes in 138 pregnant women diagnosed with TA (study group) were compared with those in 138 randomly selected healthy controls. The outcomes were also compared according to SH presence as revealed by ultrasonography (USG) in the first trimester.Results: The groups were demographically homogeneous. The mean infant weight and 1st-minute Apgar score were lower and the low-birth-weight infant rate was higher in the study group. The SH rate was statistically significantly higher in the study group (p<0.05), while there was no significant difference between the two groups in terms of birth week, preterm labor, postmaturity, delivery type, preeclampsia, placental abruption, and 5th-minute Apgar scores (p>0.05). In the control group, there was no significant difference between women with and without SH in terms of obstetric and neonatal outcomes. In the study group, the mean 5th-minute Apgar score was found to be significantly (p=0.002) higher in pregnant women with SH than in those without.Conclusion: TA may increase the likelihood of a low-birth-weight infant and a low 1st-minute Apgar score by affecting fetal weight gain and well-being. SH alone without other risk factors does not appear to affect neonatal and obstetric outcomes in healthy pregnant women. Concomitant SH and TA without additional risk factors may positively affect 5th-minute Apgar scores.
To investigate whether the maternal serum concentration of activin A at 11-13 weeks of gestation in pregnancies that subsequently develop hypertensive disorders is different from those with a normal outcome and to examine whether any possible differences are related to uterine artery pulsatility index (PI), serum pregnancy-associated plasma protein A (PAPP-A) and serum tumor necrosis factor-alpha receptor-1 (TNF-R1).
Serum activin A, TNF-R1, PAPP-A and uterine artery PI were determined in a case-control study of 126 cases that developed preeclampsia, 88 that developed gestational hypertension and 214 controls. Results: In preeclampsia, compared to controls, uterine artery PI, serum activin A and serum TNF-R1 were higher and serum PAPP-A was lower. In gestational hypertension, compared to controls, serum activin A was higher but uterine artery PI, serum PAPP-A and serum TNF-R1 were not significantly different. There were no significant associations between serum activin A and either uterine artery PI or serum TNF-R1 in either the hypertensive groups or the controls.
The data do not support the hypothesis linking activin A with impaired trophoblastic invasion of the maternal spiral arteries, placental hypoxia and the release of cytokines which in turn cause endothelial dysfunction and the development of the clinical symptoms of the disease.
Abstract Background Linking population health data to pathology data is a new approach for the evaluation of predictive tests that is potentially more efficient, feasible and efficacious than current methods. Studies evaluating the use of first trimester maternal serum levels as predictors of complications in pregnancy have mostly relied on resource intensive methods such as prospective data collection or retrospective chart review. The aim of this pilot study is to demonstrate that record-linkage between a pathology database and routinely collected population health data sets provides follow-up on patient outcomes that is as effective as more traditional and resource-intensive methods. As a specific example, we evaluate maternal serum levels of PAPP-A and free β-hCG as predictors of adverse pregnancy outcomes, and compare our results with those of prospective studies. Methods Maternal serum levels of PAPP-A and free β-hCG for 1882 women randomly selected from a pathology database in New South Wales (NSW) were linked to routinely collected birth and hospital databases. Crude relative risks were calculated to investigate the association between low levels (multiples of the median ≤ 5th percentile) of PAPP-A or free β-hCG and the outcomes of preterm delivery (
This report presents 2005 period infant mortality statistics from the linked birth/infant death data file by a variety of maternal and infant characteristics. The linked file differs from the mortality file, which is based entirely on death certificate data.
Descriptive tabulations of data are presented and interpreted. Excluding rates by cause of death, the infant mortality rate is now published with two decimal places.
The U.S. infant mortality rate was 6.86 infant deaths per 1,000 live births in 2005, which is statistically unchanged from 6.78 in 2004. Infant mortality rates ranged from 4.89 deaths per 1,000 live births for Asian or Pacific Islander (API) mothers to 13.63 for non-Hispanic black mothers. Among Hispanics, rates ranged from 4.42 for Cuban mothers to 8.30 for Puerto Rican mothers. Infant mortality rates were higher for infants who were born in multiple deliveries or whose mothers were born in the 50 states and the District of Columbia or were unmarried. Infant mortality was also higher for male infants and infants born preterm or at low birthweight. The neonatal mortality rate was essentially unchanged from 2004 (4.52) to 2005 (4.54). The postneonatal mortality rate increased 3 percent from 2.25 in 2004 to 2.32 in 2005. Infants born at the lowest gestational ages and birthweights have a large impact on overall U.S. infant mortality. For example, more than one-half (55 percent) of all infant deaths in the United States in 2005 occurred to the 2 percent of infants born very preterm (less than 32 weeks of gestation). Infant mortality rates for late preterm infants (34-36 weeks of gestation) were three times those for term infants (37-41 weeks). The three leading causes of infant death--congenital malformations, low birthweight, and sudden infant death syndrome (SIDS)--accounted for 44 percent all infant deaths. The percentage of infant deaths that were "preterm-related" increased from 34.6 percent in 2000 to 36.5 percent in 2005. The preterm-related infant mortality rate for non-Hispanic black mothers was 3.4 times higher and the rate for Puerto Rican mothers was 87 percent higher than the rate for non-Hispanic white mothers.
The risk of adverse perinatal outcome among 8839 women recruited to a multicenter, prospective cohort study was related to maternal circulating concentrations of trophoblast-derived proteins at 8-14 wk gestation. Women with a pregnancy-associated plasma protein A (PAPP-A) in the lowest fifth percentile at 8-14 wk gestation had an increased risk of intrauterine growth restriction [adjusted odds ratio, 2.9; 95% confidence interval (CI), 2.0-4.1], extremely premature delivery (adjusted odds ratio, 2.9; 95% CI, 1.6-5.5), moderately premature delivery (adjusted odds ratio, 2.4; 95% CI, 1.7-3.5), preeclampsia (adjusted odds ratio, 2.3; 95% CI, 1.6-3.3), and stillbirth (adjusted odds ratio, 3.6; 95% CI, 1.2-11.0). The strengths of the associations were similar when the test was performed before 13 wk gestation or between 13 and 14 wk gestation. In contrast, levels of free beta-human CG, another circulating protein synthesized by the syncytiotrophoblast, were not predictive of later outcome in multivariate analysis. PAPP-A has been identified as a protease specific for IGF binding proteins. We conclude that control of the IGF system in the first and early second trimester trophoblast may have a key role in determining subsequent pregnancy outcome.
In a study to evaluate the reproducibility and accuracy of the sonar technique of measurement of the in vivo fetal crown-rump length (Robinson, 1973), a series of in vivo and in vitro experiments was performed in which the random and systematic errors inherent in the technique were assessed. The potential sources of random error were those of operator judgement, movement of the fetus and mother, machine sensitivity settings and measurement from the photograph; while the sources of systematic error were those of oscilloscope scale factor, and velocity calibration inaccuracies, and the effect of beam width. The overall effect of the random errors, that is, the reproducibility of the technique, was assessed in an in vivo blind trial in which three independent measurements were made of the fetus. In a series of 30 experiments the average standard deviation of the three readings was found to be 1.2 mm. Evaluation of the systematic errors by in vivo experimentation, on the other hand, showed that the basic sonar measurements were in error by an overestimate of 1 mm for the beam width effect and 3.7 per cent for the scale factor and velocity calibration errors. A weighted non-linear regression analysis of 334 measurements was performed in order to obtain a "curve of best fit" for the period covering 6 to 14 weeks of menstrual age. The values obtained were corrected for the systematic errors and compared with widely quoted anatomical figures. In the second part of this investigation the original data was further analyzed to determine on a statistical basis the accuracy of the technique as a method of estimating maturity. It was shown that such an estimate could be made to within 4.7 days with a 95 per cent probability on the basis of a single measurement, and to within 2.7 days if three independent measurements were made.
Objective.
—To investigate the effect of advancing maternal age on pregnancy outcome among healthy nulliparous women, after adjustment for demographic characteristics, smoking, history of infertility, and other medical conditions.Design.
—A population-based cohort study was conducted with prospectively collected data from the Swedish Medical Birth Register.Patients.
—Nulliparous Nordic women (N=173715), aged 20 years and above, who delivered single births at Swedish hospitals from 1983 through 1987.Outcome Measures.
—Late fetal and early neonatal death rates; rates of very low birth weight (VLBW, <1500 g), moderately low birth weight (MLBW, 1500 through 2499 g), very preterm delivery (≤32 weeks), moderately preterm delivery (33 through 36 weeks), and small-for-gestational-age (SGA) infants (<-2 SDs).Results.
—Compared with women aged 20 to 24 years, women aged 30 to 34 years had significantly higher adjusted odds ratios (ORs) of late fetal deaths (OR=1.4); VLBW (OR=1.2); MLBW (OR=1.4); very preterm birth (OR=1.2); and SGA infants (OR=1.4). Among women aged 35 to 39 years, the adjusted OR was significantly higher for VLBW (OR=1.9); MLBW (OR=1.7); very preterm birth (OR=1.7); moderately preterm birth (OR=1.2); and SGA infants (OR=1.7). Among women 40 years old and older, the adjusted OR was significantly higher for VLBW (OR=1.8); MLBW (OR=2.0); very preterm birth (OR=1.9); moderately preterm birth (OR=1.5); and SGA infants (OR=1.4).Conclusions.
—Delayed childbearing is associated with an increased risk of poor pregnancy outcomes after adjustment for maternal complications and other risk factors.(JAMA. 1992;268:886-890)
The purpose of this case–control study was to examine the association of first-trimester concentrations of free β-human chorionic gonadotropin (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum with subsequent preterm delivery or small-for-gestational age (SGA) fetuses. We collected all the blood samples before chorionic villus sampling in the first trimester. Concentrations of free β-hCG and PAPP-A were expressed in multiples of the median (MOM) for gestational age. We compared the levels of both analytes in 73 SGA pregnancies (birth weight below the fifth percentile) with those in 292 normal controls, who were matched for gestational age, maternal age, parity, maternal weight, and smoking habits. We also compared the levels in 87 pregnancies with a preterm delivery (delivery before 37 completed weeks) with those in 348 matched controls. The median concentrations of PAPP-A and free β-hCG, expressed in MOMs, in the 73 SGA pregnancies were 0·83 and 0·95, respectively, compared with 0·98 and 1·01, respectively, in the 292 matched controls (P=0·08 and 0·19, respectively). In the 87 pregnancies with a preterm delivery, the median concentrations of PAPP-A and free β-hCG were 0·98 and 0·94, respectively, compared with 0·99 and 0·99, respectively, in the 348 matched controls (P=0·82 and 0·10, respectively). In contrast with the maternal serum analytes used in second-trimester screening—alpha-fetoprotein and human chorionic gonadotropin—this study showed that concentrations of PAPP-A and free β-hCG in the first trimester were not associated with subsequent fetal growth retardation or preterm delivery.
Objective: We sought to evaluate the association between prior spontaneous preterm delivery and subsequent pregnancy outcome. Study Design: A total of 1711 multiparous women with singleton gestations were prospectively evaluated at 23 to 24 weeks’ gestation. Prior pregnancies were coded for the presence or absence of a prior spontaneous preterm delivery. If a prior spontaneous preterm delivery had occurred, the gestation of the earliest prior delivery (13-22, 23-27, 28-34, and 35-36 weeks’ gestation) was recorded. Current gestations were categorized as spontaneous preterm delivery at
Background
Prenatal diagnosis of trisomy 21 currently relies on assessment of risk followed by invasive testing in the 5% of pregnancies at the highest estimated risk. Selection of the high-risk group by a combination of maternal age and second-trimester maternal serum biochemistry gives a detection rate of about 60%. We investigated assessment of risk by a combination of maternal age and fetal nuchal-translucency thickness, measured by ultrasonography at 10–14 weeks of gestation.
Methods
The risk of trisomy 21 was estimated for 96127 women of median age 31 years (range 14–49) with singleton pregnancies. Ultrasonography was done by 306 appropriately trained sonographers in 22 centres. Risk of trisomy 21 was calculated from the maternal age and gestational-age-related prevalence, multiplied by a likelihood ratio depending on the deviation from normal in nuchal-translucency thickness for crown-rump length. The distribution of risks was investigated and the sensitivity of a cut-off risk of 1 in 300 was calculated. Phenotype was assessed by fetal karyotyping or clinical examination of liveborn infants.
Findings
The estimated trisomy-21 risk, from maternal age and fetal nuchal-translucency thickness, was 1 in 300 or higher in 7907 (8·3%) of 95 476 normal pregnancies, 268 (82·2%) of 326 with trisomy 21, and 253 (77·9%) of 325 with other chromosomal defects. The 5% of the study population with the highest estimated risk included 77% of trisomy-21 cases.
Interpretation
Selection of the high-risk group for invasive testing by this method allows the detection of about 80% of affected pregnancies. However, even this method of risk assessment requires about 30 invasive tests for identification of one affected fetus.
To evaluate the performance of screening for pre-eclampsia by uterine artery pulsatility index (PI) at 11 + 0 to 13 + 6 weeks' gestation and the change in uterine artery PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks.
In 3107 singleton pregnancies attending for routine care at 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks' gestation we recorded maternal characteristics and medical and obstetric history, and measured uterine artery PI. The distributions of uterine artery PI were made Gaussian after logarithmic transformation and the log of the ratio of uterine artery PI at 21 + 0 to 24 + 6 weeks to that at 11 + 0 to 13 + 6 weeks was calculated. Multiple regression analysis was used to determine which of the maternal variables and Doppler findings were significant predictors of early and late pre-eclampsia. The performance of screening was described by receiver-operating characteristics curves.
Pre-eclampsia developed in 93 (3.0%) pregnancies, including 22 (0.7%) in which delivery was before 34 weeks (early pre-eclampsia) and 71 (2.3%) with delivery at 34 weeks or more (late pre-eclampsia). Seventy-three (2.3%) women developed gestational hypertension, 346 (11.1%) delivered small-for-gestational-age (SGA) babies with no hypertensive disorders and 2595 (83.5%) were unaffected by pre-eclampsia, gestational hypertension or SGA. Multiple regression analysis demonstrated that maternal variables, uterine artery PI at 11 + 0 to 13 + 6 weeks and the change in uterine artery PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks' gestation provided significant independent contributions to the prediction of pre-eclampsia. For a false positive rate of 5% the predicted detection rates of early and late pre-eclampsia were 90.9 and 31.0%, respectively. The same performance of screening was achieved by reserving second-trimester testing for only the 20% of women at the highest risk after first-trimester screening.
The decrease in uterine artery PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks is steeper in pregnancies with a normal outcome than in those developing pre-eclampsia. Effective screening for pre-eclampsia can be achieved by the Doppler measurement of uterine artery PI at 11 + 0 to 13 + 6 weeks and the change in PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks.
The purpose of this case-control study was to examine the association of first-trimester concentrations of free beta-human chorionic gonadotropin (free beta-hCG) and pregnancy-associated plasma protein A (PAPP-A) in maternal serum with subsequent preterm delivery or small-for-gestational age (SGA) fetuses. We collected all the blood samples before chorionic villus sampling in the first trimester. Concentrations of free beta-hCG and PAPP-A were expressed in multiples of the median (MOM) for gestational age. We compared the levels of both analytes in 73 SGA pregnancies (birth weight below the fifth percentile) with those in 292 normal controls, who were matched for gestational age, maternal age, parity, maternal weight, and smoking habits. We also compared the levels in 87 pregnancies with a preterm delivery (delivery before 37 completed weeks) with those in 348 matched controls. The median concentrations of PAPP-A and free beta-hCG, expressed in MOMs, in the 73 SGA pregnancies were 0.83 and 0.95, respectively, compared with 0.98 and 1.01, respectively, in the 292 matched controls (P=0.08 and 0.19, respectively). In the 87 pregnancies with a preterm delivery, the median concentrations of PAPP-A and free beta-hCG were 0.98 and 0.94, respectively, compared with 0.99 and 0.99, respectively, in the 348 matched controls (P=0.82 and 0.10, respectively). In contrast with the maternal serum analytes used in second-trimester screening--alpha-fetoprotein and human chorionic gonadotropin--this study showed that concentrations of PAPP-A and free beta-hCG in the first trimester were not associated with subsequent fetal growth retardation or preterm delivery.
To develop models for prediction of pre-eclampsia (PE) based on maternal factors and biophysical and biochemical markers at 11-13 weeks' gestation.
Screening study of singleton pregnancies at 11-13 weeks including 752 (2.2%) that subsequently developed PE and 32,850 that were unaffected by PE. Models were developed for the prediction of early PE, requiring delivery before 34 weeks, intermediate PE with delivery at 34-37 weeks and late PE delivering after 37 weeks. The data used for the models were firstly, maternal characteristics and history, uterine artery pulsatility index, mean arterial pressure and serum pregnancy-associated plasma protein-A obtained from the screening study and secondly, maternal serum or plasma concentration of placental growth factor, placental protein-13, inhibin-A, activin-A, soluble endoglin, pentraxin-3 and P-selectin obtained from case-control studies.
In screening for PE by maternal factors only at a fixed false positive rate of 5%, the estimated detection rates were 33.0% for early PE, 27.8% for intermediate PE and 24.5% for late PE. The respective detection rates in screening by a combination of maternal factors, biophysical and biochemical markers were 91.0, 79.4 and 60.9%.
Effective prediction of PE can be achieved at 11-13 weeks' gestation.
To define the potential value of endocervical length at 11 to 13 weeks' gestation in the prediction of spontaneous early delivery.
The lengths of the endocervix and cervico-isthmic complex were measured by transvaginal ultrasound at 11 to 13 weeks in singleton pregnancies, including 1492 that subsequently delivered after 34 weeks and 16 (1.1%) who had spontaneous delivery before 34 weeks. In 1320 of the cases, the measurements were repeated at 20 to 24 weeks.
There were significant associations in the length of the endocervix and cervico-isthmic complex between 11 to 13 and 20 to 24 weeks (r = 0.548, p < 0.0001 and r = 0.194, p < 0.0001), and the respective median lengths were 32.4 and 32.2 mm for the endocervix and 45.3 and 40.4 mm for the cervico-isthmic complex. At 11 to 13 weeks in the early delivery group, compared to unaffected pregnancies, the median endocervical length was shorter (27.5 vs 32.5 mm, p < 0.0001), but there was no significant difference in the length of the cervico-isthmic complex (41.4 vs 45.4 mm, p = 0.054).
In the measurement of cervical length, the endocervix should be distinguished from the isthmus. The endocervical length at 11 to 13 weeks is shorter in pregnancies resulting in spontaneous delivery before 34 weeks than in those delivering after 34 weeks.
To investigate the associations between four defined adverse pregnancy outcomes and levels of first and second trimester maternal serum markers focusing in particular on how well combinations of markers predict these adverse outcomes.
This was a retrospective review of associations between first and second trimester serum markers and adverse pregnancy outcomes among 141 698 women who underwent prenatal screening for Down syndrome in Ontario, Canada. Detection rates (DR), false positive rates (FPR), and odds ratios were estimated using both single and combinations of markers for the adverse outcomes defined.
Women with decreased second trimester unconjugated oestriol (uE3), deceased first trimester maternal serum pregnancy-associated plasma protein A (PAPP-A), increased second trimester serum alpha fetoprotein (AFP), or increased second trimester total human chorionic gonadotrophin (hCG) were at greater risk of developing adverse pregnancy outcomes. At a 5% FPR, combinations of these markers predicted at best 33.3% of fetal loss and 31.5% of preterm births (PTB) before 32 weeks of gestation.
There are significant associations between the levels of first and second trimester serum markers and adverse obstetric outcomes. However, even combinations of these markers can only predict adverse obstetric outcomes with modest accuracy.
To determine if development of preeclampsia is preceded by altered maternal plasma P-selectin and if the levels are related with uterine artery pulsatility index.
Plasma P-selectin and uterine artery pulsatility index were measured at 11-13 weeks in 121 cases that subsequently developed preeclampsia, 87 cases that developed gestational hypertension and 208 unaffected controls.
In the preeclampsia group the median multiple of the median in controls (MoM) P-selectin and uterine artery PI were significantly increased (1.2 MoM and 1.3 MoM). There was no significant association between P-selectin and uterine artery pulsatility index in either the preeclampsia or control group.
In pregnancies that develop preeclampsia there is evidence of platelet activation from the first trimester. However, there is no direct link between the degree of impaired placentation and platelet activation.
To determine the association of, and predictive ability of, pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin (beta-hCG), and nuchal translucency (NT) with preterm birth (PTB).
A 5-year retrospective cohort study of women who underwent first-trimester combined screening was performed. Maternal medical, antepartum, and pregnancy outcome data were obtained. PAPP-A and beta-hCG were converted to multiples of the median (MoM), and primary exposure was defined as < or =10th percentile MoM for PAPP-A. Secondary exposures were defined as > or = 90th percentile MoM for beta-hCG and NT values of > or = 20 and 25 mm. The primary outcome was PTB before 35 weeks and the secondary outcome was PTB before 32 weeks. Univariate, bivariate, multivariate, and receiver-operator analyses were used.
Of the 2231 patients meeting inclusion criteria with complete outcome data available, 222 had a PAPP-A level < or =10th percentile MoM. Abnormally low PAPP-A was associated with an increased risk for PTB < 35 weeks [adjusted odds ratio (aOR) 2.0, 1.0-3.8] and < 32 weeks (aOR 2.7, 1.1-6.4), even after adjusting for prior PTB, tobacco exposure, chronic hypertension, and body mass index. PAPP-A < or =10th percentile was not sufficiently predictive of PTB < 35 weeks (area under curve = 0.63, 95% CI 0.53-0.72). Neither abnormally high beta-hCG nor increased NT was associated with an increased risk for PTB.
PAPP-A < or =10th percentile is associated with an increased risk for PTB, but is not sufficiently predictive to be used clinically.
Wide disparities in obstetric outcomes exist between women of different race/ethnicities. The prevalence of preterm birth, fetal growth restriction, fetal demise, maternal mortality, and inadequate receipt of prenatal care all vary by maternal race/ethnicity. These disparities have their roots in maternal health behaviors, genetics, the physical and social environments, and access to and quality of health care. Elimination of the health inequities because of sociocultural differences or access to or quality of health care will require a multidisciplinary approach. We aim to describe these obstetric disparities, with an eye toward potential etiologies, thereby improving our ability to target appropriate solutions.
We investigated the association between prenatal smoking and the occurrence of medically indicated and spontaneous preterm delivery (<37 weeks). We performed a retrospective cohort study of singleton live births in the state of Missouri (n = 1,219,159) using maternally linked cohort data files covering the period 1989 to 2005. The main outcomes of interest were spontaneous and medically indicated preterm and very preterm birth. Logistic regression models were used to generate adjusted odds ratios and their 95% confidence intervals. There were 132,246 (10.8%) infants born preterm in the study population, of which 106,410 (80.5%) were classifiable as spontaneous preterm births and 25,836 (19.5%) were medically indicated preterm deliveries. We found elevated risks for both medically indicated and spontaneous preterm birth associated with maternal cigarette smoking during pregnancy. This heightened risk was particularly evident for medically indicated preterm birth (adjusted odds ratio [95% confidence interval] = 1.48 [1.41 to 1.55]). Women who smoke during pregnancy are at increased risk for preterm birth, and especially for medically indicated preterm delivery.
An imbalance between angiogenic and anti-angiogenic factors in maternal blood has been observed in several obstetrical syndromes including preeclampsia, pregnancies with fetal growth restriction and fetal death. Vascular lesions have been identified in a subset of patients with spontaneous preterm labor (PTL). It is possible that PTL may be one of the manifestations of an anti-angiogenic state. The aim of this study was to determine if patients prior to the clinical diagnosis of PTL leading to preterm delivery had plasma concentrations of angiogenic and anti-angiogenic factors different from normal pregnant women.
This longitudinal nested case-control study included normal pregnant women (n = 208) and patients with PTL leading to preterm delivery (n = 52). Maternal blood samples were collected at 6 gestational age intervals from 6 to 36.9 weeks of gestation. The end point (time of diagnosis) of the study, 'True PTL', was defined as patients presenting with PTL and delivered within 1 day. Plasma concentrations of sVEGFR-1, sVEGFR-2, sEng and PlGF were determined by ELISA. Analysis was performed with both cross-sectional and longitudinal (mixed effects model) approaches.
(1) Plasma sEng concentration in patients destined to develop PTL was higher than that in normal pregnant women from 15-20 weeks of gestation. The difference became statistical significant at 28 weeks of gestation, or approximately 5-10 weeks prior to the diagnosis of 'true PTL'. (2) Backward analysis suggests that plasma concentrations of PlGF and sVEGFR-2 were lower, and those of sVEGFR-1 were higher in patients with PTL than in normal pregnant women less than 5 weeks prior to the diagnosis of 'true PTL'; and (3) Plasma concentrations of sEng and sVEGFR-1 were higher and those of PlGF and sVEGFR-2 were lower in patients diagnosed with PTL and delivery within 1 day than in normal pregnant women who delivered at term.
The changes in sEng are demonstrable several weeks prior to the onset of preterm parturition. In contrast, the changes in the other angiogenic proteins are present close to the onset of PTL and delivery. This observation supports the view that an imbalance of angiogenic factors participates in the pathophysiology of spontaneous preterm parturition.
To examine the potential value of maternal serum concentration of placental protein 13 (PP13) at 11-13 weeks' gestation in screening for preeclampsia (PE).
Serum PP13, PAPP-A and uterine artery pulsatility index (PI) were determined in a case-control study of 208 cases that developed PE including 48 that required delivery before 34 weeks (early-PE) and 416 unaffected controls.
Serum PP13 levels, expressed as multiples of the median (MoM) in the unaffected group, were significantly reduced in early-PE (0.83 MoM) but not in late-PE (0.96 MoM). In both early- and late-PE serum PAPP-A (0.55 and 0.84 MoM) was reduced and uterine artery PI (1.61 and 1.25 MoM) was increased. In PE pregnancies there was a significant association between serum PP13 and both uterine artery PI and serum PAPP-A (p < 0.0001 for both). Logistic regression analysis demonstrated that serum PP13 did not improve significantly the prediction of early-PE provided by a combination of maternal factors, uterine artery PI and PAPP-A.
PP13 is implicated in the pathogenesis of impaired placentation and subsequent development of early-PE but measurement of this placental product is unlikely to be useful in screening for the disease at 11-13 weeks.
To investigate the potential value of maternal plasma inhibin A in first-trimester screening for preeclampsia (PE).
The concentration of inhibin A at 11-13 weeks was measured in samples from 121 pregnancies that developed PE, 87 cases of gestational hypertension (GH) and 208 normal controls. The distributions of inhibin A multiple of median (MoM) in the control and hypertensive groups were compared. Logistic regression analysis was used to derive algorithms for the prediction of hypertensive disorders.
The maternal plasma inhibin A MoM was significantly higher in the early and late PE groups (1.55 MoM and 1.24 MoM, respectively; p < 0.0083), compared to the controls (0.98 MoM), but not in GH. Significant contributions for the prediction of PE were provided by maternal factors, plasma inhibin A and uterine artery pulsatility index (PI) and with combined screening the detection rates for early and late PE were 88% and 42%, respectively, for a false positive rate of 10%.
The proposed combined screening test could be used to identify women at high risk for PE and intensive monitoring in such patients would lead to earlier identification of the disease which could potentially improve pregnancy outcome.
To examine the relationship between low maternal serum pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (UtA-PI) at 11+0 to 13+6 weeks with subsequent development of pre-eclampsia (PE).
UtA-PI and serum PAPP-A were measured in women attending for routine care at 11+0 to 13+6 weeks of gestation. In the population, 156 (1.9%) women developed PE, including 32 (0.4%) in whom delivery was before 34 weeks (early PE) and 124 (1.5%) with delivery at 34 weeks or more (late PE); 7895 (98.1%) women had no PE. Regression analysis was used to examine which of the factors amongst maternal characteristics, log PAPP-A multiples of the median (MoM) and log UtA-PI MoM contributed to the prediction of PE.
The median PAPP-A MoM was 1.002 (interquartile range (IQR), 0.685-1.411) in the unaffected group, 0.555 (IQR, 0.463-0.922) in early PE and 0.911 (IQR, 0.580-1.247) in late PE. Serum PAPP-A was below the 5th centile in 21.9% of early PE and 6.5% of late PE cases. The PAPP-A-related patient-specific risk for PE was strongly influenced by maternal characteristics. There was a significant association between log UtA-PI MoM and log PAPP-A MoM (P=0.001), and the detection rate of screening for PE by maternal variables and UtA-PI was not improved by inclusion of PAPP-A. Regression analysis was used to establish tables that allow modification of the maternal history and PAPP-A-related patient-specific risk for PE by the measurement of UtA-PI.
Low PAPP-A is a marker for subsequent development of PE. The PAPP-A-related patient-specific risk for PE can be modified by the measurement of UtA-PI.
To examine the possible association of maternal serum a disintegrin and metalloprotease (ADAM12) in the first trimester of pregnancy and subsequent development of preeclampsia, delivery of small for gestational age (SGA) neonates, and spontaneous preterm delivery.
The maternal serum concentration of ADAM12 at 11 0/7 to 13 6/7 weeks was measured in 128 cases of preeclampsia, 88 cases of gestational hypertension, 296 cases with SGA neonates, 58 cases of spontaneous preterm delivery, and 570 controls. Regression analysis was used to determine which of the maternal factors and fetal crown rump length were significant predictors of ADAM12 in the control group, and from the regression model the value in each case and control was expressed as a multiple of median (MoM). The levels of ADAM12 MoM were compared in cases and controls.
In the control group the concentration of ADAM12 increased with fetal crown rump length, decreased with maternal weight and was higher in African-American than in white women. There was a significant association between ADAM12 and pregnancy-associated plasma protein A (r=0.417, P<.001) and between each metabolite and birth weight percentile (r=0.176, P<.001 and r=0.109, P=.009). In the SGA group, the median ADAM12 concentration (0.848 MoM) was lower (P<.001), but in pregnancies complicated by preeclampsia (0.954 MoM), gestational hypertension (1.013 MoM), and spontaneous preterm delivery (1.048 MoM) the levels were not significantly different from controls (1.011 MoM).
There is a good correlation between the maternal serum ADAM12 and pregnancy-associated plasma protein A concentration. Measurement of ADAM12 does not provide useful prediction of SGA, preeclampsia, or spontaneous preterm delivery.
II.
To investigate the potential value of maternal serum placental growth factor (PlGF) in first-trimester screening for pre-eclampsia (PE).
The concentration of PlGF at 11 + 0 to 13 + 6 weeks' gestation was measured in samples from 127 pregnancies that developed PE, including 29 that required delivery before 34 weeks (early PE) and 98 with late PE, 88 cases of gestational hypertension (GH) and 609 normal controls. The distributions of PlGF multiples of the median (MoM) in the control and hypertensive groups were compared. Logistic regression analysis was used to determine the factors with a significant contribution for predicting PE.
In the control group significant independent contributions for log PlGF were provided by fetal crown-rump length, maternal weight, cigarette smoking and racial origin, and after correction for these variables the median MoM PlGF was 0.991. In the early-PE and late-PE groups PlGF (0.611 MoM and 0.822 MoM, respectively; P < 0.0001) and pregnancy-associated plasma protein-A (PAPP-A) (0.535 MoM; P < 0.0001 and 0.929 MoM; P = 0.015, respectively) were reduced but in GH (PlGF: 0.966 MoM; PAPP-A: 0.895 MoM) there were no significant differences from controls. Significant contributions for the prediction of PE were provided by maternal characteristics and obstetric history, serum PlGF and uterine artery pulsatility index (PI) and with combined screening the detection rates for early PE and late PE were 90% and 49%, respectively, for a false-positive rate of 10%.
Effective screening for PE can be provided by a combination of maternal characteristics and obstetric history, uterine artery PI and maternal serum PlGF at 11 + 0 to 13 + 6 weeks' gestation.
Patients with a history of two or more pregnancies which ended spontaneously before 37 weeks gestation had an increased risk of spontaneous pre-term labour and delivery in future pregnancies. This increased risk related mainly to previous second trimester abortions and not to previous first trimester abortions. Patients with one previous spontaneous pre-term labour and delivery had a 37 per cent risk, and those with two or more pre-term deliveries a 70 per cent risk of again delivering pre-term. There appeared to be no beneficial effect of cervical suture on the incidence of pre-term delivery in these patients.
In a study to evaluate the reproducibility and accuracy of the sonar technique of measurement of the in vivo fetal crown-rump length (Robinson, 1973), a series of in vivo and in vitro experiments was performed in which the random and systematic errors inherent in the technique were assessed. The potential sources of random error were those of operator judgement, movement of the fetus and mother, machine sensitivity settings and measurement from the photograph; while the sources of systematic error were those of oscilloscope scale factor, and velocity calibration inaccuracies, and the effect of beam width. The overall effect of the random errors, that is, the reproducibility of the technique, was assessed in an in vivo blind trial in which three independent measurements were made of the fetus. In a series of 30 experiments the average standard deviation of the three readings was found to be 1.2 mm. Evaluation of the systematic errors by in vivo experimentation, on the other hand, showed that the basic sonar measurements were in error by an overestimate of 1 mm for the beam width effect and 3.7 per cent for the scale factor and velocity calibration errors. A weighted non-linear regression analysis of 334 measurements was performed in order to obtain a "curve of best fit" for the period covering 6 to 14 weeks of menstrual age. The values obtained were corrected for the systematic errors and compared with widely quoted anatomical figures. In the second part of this investigation the original data was further analyzed to determine on a statistical basis the accuracy of the technique as a method of estimating maturity. It was shown that such an estimate could be made to within 4.7 days with a 95 per cent probability on the basic of a single measurement, and to within 2.7 days if three independent measurements were made.
To investigate the effect of advancing maternal age on pregnancy outcome among healthy nulliparous women, after adjustment for demographic characteristics, smoking, history of infertility, and other medical conditions.
A population-based cohort study was conducted with prospectively collected data from the Swedish Medical Birth Register.
Nulliparous Nordic women (N = 173,715), aged 20 years and above, who delivered single births at Swedish hospitals from 1983 through 1987.
Late fetal and early neonatal death rates; rates of very low birth weight (VLBW, less than 1500 g), moderately low birth weight (MLBW, 1500 through 2499 g), very preterm delivery (less than or equal to 32 weeks), moderately preterm delivery (33 through 36 weeks), and small-for-gestational-age (SGA) infants (less than -2 SDs).
Compared with women aged 20 to 24 years, women aged 30 to 34 years had significantly higher adjusted odds ratios (ORs) of late fetal deaths (OR = 1.4); VLBW (OR = 1.2); MLBW (OR = 1.4); very preterm birth (OR = 1.2); and SGA infants (OR = 1.4). Among women aged 35 to 39 years, the adjusted OR was significantly higher for VLBW (OR = 1.9); MLBW (OR = 1.7); very preterm birth (OR = 1.7); moderately preterm birth (OR = 1.2); and SGA infants (OR = 1.7). Among women 40 years old and older, the adjusted OR was significantly higher for VLBW (OR = 1.8); MLBW (OR = 2.0); very preterm birth (OR = 1.9); moderately preterm birth (OR = 1.5); and SGA infants (OR = 1.4).
Delayed childbearing is associated with an increased risk of poor pregnancy outcomes after adjustment for maternal complications and other risk factors.
To evaluate if idiopathic spontaneous preterm delivery is associated with abnormal uteroplacental circulation, as assessed by Doppler velocimetry.
The study was carried out on 417 women who had Doppler velocimetry performed between 25-36 weeks' gestation and were subsequently delivered vaginally. The systolic-diastolic ratio (S/D) was computed for the uterine and umbilical arteries, and the outcomes of pregnancies with spontaneous preterm and term deliveries were compared.
Uterine artery S/D was significantly higher (P < .0001) in the 31 patients delivered preterm, whereas no significant difference was observed in the umbilical S/D. Abnormal values of uterine S/D were detected in 58.1% of the preterm group, independent of the gestational age at examination. No significant increase in S/D was observed in patients hospitalized for preterm labor who delivered subsequently at term. Spontaneous preterm delivery was associated with increased uterine S/D among both pregnancies with small for gestational age fetuses and those with appropriately grown fetuses.
Preterm delivery is associated with modifications of uterine artery Doppler velocimetry, suggesting that impaired trophoblastic invasion of the placental bed may play a role in determining preterm delivery.
Our aim was to find out whether patients delivered preterm because of preterm labor or preterm premature rupture of membranes can be categorized according to clinical characteristics and placental pathologic findings.
We performed a case-control study of 105 patients who were delivered preterm, 42 because of preterm labor and 63 because of premature rupture of membranes, and 105 patients who were delivered at term after uncomplicated pregnancies.
Maternal placental vascular lesions were present in 14 (34.1%) patients with preterm labor, 19 (35.1%) patients with premature rupture of membranes, and 9 (11.8%) control patients (odds ratios 3.8 and 4.0, 95% confidence intervals 1.3 to 11.1 and 1.5 to 10.8, p = 0.0065 and 0.0022, respectively). Infection of the products of conception was found in 16 patients (38%) with preterm labor, 23 patients (36.5%) with premature rupture of membranes, and 19 control patients (18%) (odds ratios 2.7 and 2.6, 95% confidence intervals 1.1 to 6.6 and 1.2 to 5.6, p = 0.017 and 0.01, respectively). Patients with maternal placental vasculopathy had significantly different characteristics compared with those of infected patients.
It is possible to identify two subgroups of patients among those who are delivered preterm because of preterm labor or premature rupture of membranes, one with infection of the products of conception and another with maternal placental vasculopathy.
The role of the cervix in the pathogenesis of premature delivery is controversial. In a prospective, multicenter study of pregnant women, we used vaginal ultrasonography to measure the length of the cervix; we also documented the incidence of spontaneous delivery before 35 weeks' gestation.
At 10 university-affiliated prenatal clinics, we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies. We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery.
We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks. Spontaneous preterm delivery (at less than 35 weeks) occurred in 126 of the women (4.3 percent) examined at 24 weeks. The length of the cervix was normally distributed at 24 and 28 weeks (mean [+/- SD], 35.2 +/- 8.3 mm and 33.7 +/- 8.5 mm, respectively). The relative risk of preterm delivery increased as the length of the cervix decreased. When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile, the relative risks of preterm delivery among the women with shorter cervixes were as follows: 1.98 for cervical lengths at or below the 75th percentile (40 mm), 2.35 for lengths at or below the 50th percentile (35 mm), 3.79 for lengths at or below the 25th percentile (30 mm), 6.19 for lengths at or below the 10th percentile (26 mm), 9.49 for lengths at or below the 5th percentile (22 mm), and 13.99 for lengths at or below the 1st percentile (13 mm) (P < 0.001 for values at or below the 50th percentile; P = 0.008 for values at or below the 75th percentile). For the lengths measured at 28 weeks, the corresponding relative risks were 2.80, 3.52, 5.39, 9.57, 13.88, and 24.94 (P < 0.001 for values at or below the 50th percentile; P = 0.003 for values at the 75th percentile).
The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy.
Premature rupture of membranes arises from what are likely multifaceted and multistep pathogenic pathways. Pathophysiological processes may involve both endogenous and exogenous fetal and maternal factors. This article reviews and analyzes information regarding, first, the form and function of fetal membranes; second, how membranes physically fail (rupture) at term and preterm gestations; and third, evaluates if we can reduce risks of rupture using physiological understanding and evidence-based clinical studies.
To analyze the placental histology in cases of preterm premature rupture of membranes (PROM), classify the cases according to the results of the histologic examination, and determine if these histologic groups have different clinical characteristics and outcomes.
During a 3-year period, a cohort of 235 women with preterm PROM was studied prospectively. The women were classified according to placental histologic findings, and their prenatal and intrapartum courses and perinatal mortality and morbidity were analyzed and compared.
One hundred two placentas (43.4%) exhibited acute inflammatory lesions, 48 (20.4%) had vascular lesions, 48 (20.4%) had both inflammatory and vascular lesions, 31 (13.2%) had no abnormal findings, four (1.7%) had villous edema, and two (0.8%) had chronic villitis. The four largest histologic groups had distinctive characteristics with respect to gestational age at the time of PROM and at delivery, duration of the latency period, and perinatal mortality and morbidity.
Cases of preterm PROM may be classified according to placental histologic findings, and these groups have different clinical manifestations, prognoses, and outcomes.
Prenatal diagnosis of trisomy 21 currently relies on assessment of risk followed by invasive testing in the 5% of pregnancies at the highest estimated risk. Selection of the high-risk group by a combination of maternal age and second-trimester maternal serum biochemistry gives a detection rate of about 60%. We investigated assessment of risk by a combination of maternal age and fetal nuchal-translucency thickness, measured by ultrasonography at 10-14 weeks of gestation.
The risk of trisomy 21 was estimated for 96127 women of median age 31 years (range 14-49) with singleton pregnancies. Ultrasonography was done by 306 appropriately trained sonographers in 22 centres. Risk of trisomy 21 was calculated from the maternal age and gestational-age-related prevalence, multiplied by a likelihood ratio depending on the deviation from normal in nuchal-translucency thickness for crown-rump length. The distribution of risks was investigated and the sensitivity of a cut-off risk of 1 in 300 was calculated. Phenotype was assessed by fetal karyotyping or clinical examination of liveborn infants.
The estimated trisomy-21 risk, from maternal age and fetal nuchal-translucency thickness, was 1 in 300 or higher in 7907 (8.3%) of 95476 normal pregnancies, 268 (82-2%) of 326 with trisomy 21, and 253 (77.9%) of 325 with other chromosomal defects. The 5% of the study population with the highest estimated risk included 77% of trisomy-21 cases.
Selection of the high-risk group for invasive testing by this method allows the detection of about 80% of affected pregnancies. However, even this method of risk assessment requires about 30 invasive tests for identification of one affected fetus.
We assessed several variables as predictors for pre-eclampsia risk in a group of women at high risk.
We studied 2503 women with either diabetes mellitus, chronic hypertension, multifetal gestation, or pre-eclampsia in a previous pregnancy who participated in a multicenter study comparing aspirin and placebo in preventing pre-eclampsia. We evaluated multiple variables for predicting pre-eclampsia risk with use of univariate and multivariable analysis.
Parity and mean arterial pressure at randomization were most predictive of pre-eclampsia risk. The risk was 8% with a mean arterial pressure at enrollment of <75 mm Hg versus 27% with a mean arterial pressure >85 mm Hg (relative risk and 95% confidence interval 3.3 [2.4 to 4.4]). The risk of pre-eclampsia was 26% in nulliparous patients versus 17% in parous subjects (relative risk and 95% confidence interval 1.5 [1.3-1.8]).
The finding that second-trimester mean arterial pressure affects pre-eclampsia risk suggests that the pathophysiologic process of preeclampsia is initiated before that time.
To examine the potential value of routine measurement of cervical length in singleton pregnancies at 23 weeks of gestation in the prediction of the risk for early spontaneous preterm delivery.
Cervical length was measured by sonography at 23 weeks in 2567 singleton pregnancies in women attending for routine antenatal care. In 43 women, the length was < or = 15 mm and 21 of these were managed expectantly, whereas in 22 cases a cervical cerclage was placed. In the pregnancies that were managed expectantly, the relation between cervical length and preterm delivery was examined and the risk of spontaneous delivery at < or = 32 weeks was estimated.
Cervical length at 23 weeks was < or = 15 mm in 1.7% of cases; this group contained 86%, 58% and 20% of pregnancies that delivered spontaneously at < or = 28, < or = 32 and < or = 36 weeks, respectively. The risk for delivery at < or = 32 weeks decreased from 78% at a cervical length of 5 mm to 4% at 15 mm and 0.5% at 50 mm.
Cervical length at 23 weeks is < or = 15 mm in < 2% of the population; this group contains about 90% and 60% of the women delivering at < or = 28 and < or = 32 weeks, respectively. Measurement of cervical length provides accurate prediction of risk for early preterm delivery.
To determine the relevance of ischemia in the incidence of preterm labor. A second objective was to document perinatal outcomes for patients with preterm labor classified according to its clinical, functional, and pathologic characteristics (infectious, ischemic, mixed, or idiopathic).
Perinatal outcomes were evaluated for 145 consecutive patients with preterm labor, subdivided into etiologic categories according to clinical, functional (Doppler), and morphologic (placental pathology) characteristics. A group of 44 normal pregnancies delivered at term served as controls.
Of the preterm labor group, 28.3% were classified as ischemic, compared with 4.5% of the control group (odds ratio and 95% confidence interval = 8.28 [1.8, 51.8]; P < .05). Compared with the control group, the preterm labor patients who delivered preterm had higher rates of ischemia (31.4% compared with 4.5%; P < .05) and infection (16.1% compared with 2.3%; P < .05). Among the preterm labor group, patients classified in the infectious or ischemic subgroups had a higher rate of preterm delivery (95.0% and 90.2% compared with 73.2%; P < .05), admission to the neonatal intensive care unit (75.0% and 61.0% compared with 40.0%; P < .05), and newborn weight under 1500 g (35.0% and 19.5% compared with 3.7%; P < .05) than the idiopathic subgroup.
Preterm labor resulting from infection or ischemia is associated with a higher perinatal complication rate than idiopathic preterm labor.
We sought to evaluate the association between prior spontaneous preterm delivery and subsequent pregnancy outcome.
A total of 1711 multiparous women with singleton gestations were prospectively evaluated at 23 to 24 weeks' gestation. Prior pregnancies were coded for the presence or absence of a prior spontaneous preterm delivery. If a prior spontaneous preterm delivery had occurred, the gestation of the earliest prior delivery (13-22, 23-27, 28-34, and 35-36 weeks' gestation) was recorded. Current gestations were categorized as spontaneous preterm delivery at <28, <30, <32, <35, or <37 weeks' gestation. The risk of spontaneous preterm delivery in the current gestation was determined on the basis of the occurrence, gestational age, and cause of the earliest prior spontaneous preterm delivery.
The incidences of spontaneous preterm delivery before 28, 30, 32, 35, and 37 weeks' gestation were 0.8%, 1.1%, 1.9%, 5.1%, and 11.9%, respectively. Those with a prior spontaneous preterm delivery carried a 2.5-fold increase in the risk of spontaneous preterm delivery in the current gestation over those with no prior spontaneous preterm delivery (21. 7% vs 8.8%; P </=.001). Gravid women with an early prior spontaneous preterm delivery (23-27 weeks' gestation) had a higher risk of recurrent spontaneous preterm delivery (27.1% vs 8.8%; P </=.001). Prior spontaneous preterm delivery was more closely associated with subsequent early spontaneous preterm delivery at <28 weeks' gestation (relative risk, 10.6) than for spontaneous preterm delivery overall (relative risk, 2.5). An early prior spontaneous preterm delivery (23-27 weeks' gestation) was most highly associated with early spontaneous preterm delivery (<28 weeks' gestation) in the current gestation (relative risk, 22.1). The relationship between prior spontaneous preterm delivery and current outcome was not as strong for those with a very early spontaneous preterm delivery (13-22 weeks' gestation). Prior spontaneous preterm delivery caused by preterm premature rupture of the membranes and preterm labor was significantly associated with similar outcomes in the current gestation (P <.001).
Prior spontaneous preterm delivery is highly associated with recurrence in the current gestation. An early prior spontaneous preterm delivery is more predictive of recurrence and is most highly associated with subsequent early spontaneous preterm delivery.
We have attempted to quantify the most up-to-date estimate of the association between cigarette smoking by the mother and preterm delivery. Studies were selected for inclusion in this review if they were prospective, reported data stratified across at least two levels of maternal smoking, and defined preterm delivery on the basis of gestational age. In a meta-analysis we combined results from multiple studies that reported on preterm delivery and maternal smoking during pregnancy. Pooled odds ratios were computed for various strata of smoking intensity with the Mantel-Haenszel fixed-effects model. Twenty studies met all inclusion criteria and were included in meta-analysis. The pooled point estimate from 20 prospective studies on any maternal smoking versus no maternal smoking was 1.27 (95% confidence interval, 1.21-1.33). Subgroup analyses stratifying maternal smoking on number of cigarettes per day suggest a dose-response relationship at low to moderate levels of smoking, which was not further increased at high levels of smoking. A nonsignificant level of publication bias appears to exist in the smoking-preterm delivery literature. Cigarette smoking is a preventable risk factor that is associated with preterm delivery. Consistent results across many study populations and research designs and evidence of a dose-response relationship support its causal role in preterm delivery.
To examine the value of first trimester maternal serum free beta human chorionic gonadotrophin (beta hCG) and pregnancy associated plasma protein A (PAPP-A) as predictors of pregnancy complications.
Screening study.
Antenatal clinics.
Singleton pregnancies at 10-14 weeks of gestation.
Maternal serum free beta hCG and PAPP-A were measured at 10-14 weeks of gestation in 5,584 singleton pregnancies. In the 5,297 (94.9%) pregnancies with complete follow up free beta hCG and PAPP-A were compared between those with normal outcome and those resulting in miscarriage, spontaneous preterm delivery, pregnancy induced hypertension or fetal growth restriction and in those with pre-existing or gestational diabetes.
Maternal serum PAPP-A increased and beta hCG decreased with gestation. The multiple of median maternal serum PAPP-A was significantly lower in those pregnancies resulting in miscarriage, pregnancy induced hypertension, growth restriction and in those with pre-existing or gestational diabetes mellitus, but not in those complicated by spontaneous preterm delivery. The level was < 10th centile of the reference range in about 20% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 27% of those that developed gestational diabetes. Maternal serum free beta hCG was < 10th centile of the reference range in about 15% of the pregnancies that subsequently resulted in miscarriage or developed pregnancy induced hypertension or growth restriction, and in 20% of those that developed gestational diabetes.
Low maternal serum PAPP-A or beta hCG at 10-14 weeks of gestation are associated with subsequent development of pregnancy complications.
The purpose of this study was to determine whether failure of physiologic transformation of the spiral arteries occurs in patients with preterm premature rupture of membranes (PROM).
A cross-sectional study was designed to examine the histopathologic findings in the placental bed and placenta of patients with preterm PROM, preeclampsia, and normal women at term. Immunohistochemistry with cytokeratin 7 and periodic acid-Schiff (PAS) were used to detect trophoblast and fibrinoid and to diagnose failure of physiologic transformation of the spiral arteries.
One hundred thirteen cases met the inclusion criteria, 59 from patients with normal pregnancies, 31 with preterm PROM, and 23 with preeclampsia. The mean number of the spiral arteries with failure of physiologic transformation of the myometrial segment was significantly higher in patients with preterm PROM and preeclampsia than in normal pregnant women at term (P =.006 and P <.0001, respectively). In contrast, the mean number of the spiral arteries with failure of physiologic transformation of the decidual segment of the spiral arteries in the basal plate of the placenta was not significantly different in patients with preterm PROM from that in normal pregnant women (P >.05). Placentas from patients with preterm PROM had a higher frequency of vascular lesions than those from normal pregnant women (P =.02).
Defective placentation, defined as failure of physiologic transformation of the myometrial segment of the spiral artery, is frequently present in preterm PROM.
The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population.
A randomized, double-blind, placebo-controlled study included 142 high-risk singleton pregnancies. Progesterone (100 mg) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes, between 24 and 34 weeks of gestation. Progesterone (n = 72) and placebo (n = 70) groups were compared for epidemiologic characteristics, uterine contraction frequency, and incidence of preterm birth. Data were compared by chi(2) analysis and Fisher exact test.
The preterm birth rate was 21.1% (30/142). Differences in uterine activity were found between the progesterone and placebo groups (23.6% vs 54.3%, respectively; P <.05) and in preterm birth between progesterone and placebo (13.8% vs 28.5%, respectively; P <.05). More women were delivered before 34 weeks in the placebo group (18.5%) than in the progesterone group (2.7%) (P <.05).
Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity.