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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 resourc...
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... The levels of PAPP-A were found to be significantly lower in fetuses with Down syndrome [ 3 ]. Literature shows that low first trimester PAPP-A in patients with normal karyotype is associated with adverse perinatal outcome [ 4 ] including IUFD, spontaneous abortions [ 5 ], low birth weight, preterm labor and PE [6][7][8]. Together with maternal characteristics and mean arterial pressure they are promising markers in the risk assessment of PE, especially for the early onset, complicated by SGA [ 6 ]. ...
In Bulgaria the frst trimester Down syndrome screening was first performed in 2006. For a three years period over 13 000 pregnancies have been screened. The aim of the study is to evaluate the role of low PAPP-A levels in prediction of PE and early PE alone, or together with some risk factors. Four hundred and twenty singleton pregnancies that underwent first trimester Down syndrome screening between January 2008 and December 2010 had been analyzed. Fifty patients (11.9%) developed PE, of which 17 required delivery before 34th gw. The control group consists of 279 women who delivered
term healthy babies. The borderline for evaluation of the risk of PE is set on 0.4 MoM. Twenty out of 50 (40%) patients with PE, 11 out of 17 (64.7%) patients with early onset PE and 87 out of 279 (31.2%) controls had PAPP-A levels below this border. These levels were associated with 1.5 RR for PE development. Low first trimester PAPP-A levels alone were associated with a poor prognostic value for development of PE. Together with the maternal age and especially with uterine arteries Doppler a signifcant prognostic value improvement was found. This combination provides a good possibility for evaluation
of the patients at risk for such pregnancy complication.
... The present study found that the incidence of SGA and preterm birth increased when a PAPP-A level of less than 0.4 MoM was used as the cutoff for detection. This quintile of PAPP-A (equivalent to the 20th centile) matched the fifth centile cited in previously published studies [5,7,9,17,18], indicating that more pregnancies in the present study population had lower PAPP-A levels than did populations included in other studies. The PAPP-A cut-off defined in the present study had previously been associated with increased frequency of adverse obstetric outcomes [13]. ...
... In the present study, low PAPP-A levels were associated with both SGA and preterm birth, which is consistent with previously published data [17,20]. However, some studies have reported a statistically significant association of low PAPP-A levels with SGA only [8,21,22]. ...
Objective:
To analyze the relationship between first-trimester levels of pregnancy-associated plasma protein A (PAPP-A) and small-for-gestational-age (SGA) neonates and preterm births, and to assess predictive utility for these events.
Methods:
A prospective study was conducted among women undergoing first-trimester screening between January 1, 2012, and December 31, 2013, at two centers in Pune, India. Serum PAPP-A levels, pregnancy course, and outcome were assessed.
Results:
Overall, 1474 women were included. An association was found between the lowest quintile of PAPP-A levels (<0.4 multiples of median) for both SGA (<10th centile; 20.9% of cases in this PAPP-A quintile) and preterm birth (<37weeks; 15.8%). Women in the lowest quintile of PAPP-A concentration had a significantly increased risk of SGA (<10th centile) than did those with higher concentrations (adjusted odds ratio 2.92, 95% confidence interval 2.00-4.27). Their risk of preterm birth (<37weeks) was also increased (adjusted odds ratio 1.84, 95% confidence interval 1.25-2.72). The predictive sensitivities of the lowest quintile of PAPP-A were 35.85% for SGA (<10th centile) and 27.92% for preterm birth (<37weeks).
Conclusion:
Low levels of PAPP-A were associated with SGA and preterm births; however, poor predictive sensitivity could restrict clinical utility of this marker when used alone.
... The most accurate predictor was PAPPA < 0.4 MoM (multiples of median); LR+ 2.17 (1.48,3.17), LR-0.91 (0.85, Fig. 1 Seletion process: process from initial search to final inclusion for biochemical screening to predict pre-eclampsia/small for gestational age/preterm delievery For SGA there were 19 studies for SGA < 10 th centile and 6 studies for SGA < 5 th centile included in the meta-analysis [4,6,7,10,11,[23][24][25][26][27][28][29][30][31][32][33][34][35][36] (Fig. 4). The commonest threshold used to predict SGA < 10 th centile were PAPPA < 5 th centile (9 studies). ...
... The commonest thresholds used were hCG < 5 th (3 studies) and calculated from receiver operating curve analysis. The most accurate predictor for SGA < 10 th centile was calculated from receiver operating curve analysis; LR+ 3.44 There were 6 studies for preterm delivery [7,10,11,23,35,40] and 4 studies for preterm delivery < 34 weeks [7,23,25,40] included in the meta-analysis (Fig. 10). The commonest threshold used to predict preterm delivery were hCG < 5 th centile (6 studies). ...
Early assessment before the establishment of placental dysfunction has the potential to improve treatment and prognosis for clinical practice.The objective of the study is to investigate the accuracy of serum biochemical markers(Pregnancy- Associated Plasma Protein-A (PAPP-A), human Chorionic Gonadotropin (hCG), Placental Growth Factor (PlGF), Placental Protein 13 (PP13) used in first trimester serum screening in predicting preelampsia, small for gestational age (SGA) and preterm delivery.
The data sources included Medline, Embase, Cochrane library, Medion, hand searching of relevant journals, reference list checking of included articles and contact with experts. Two reviewers independently selected the articles. Two authors independently extracted data on study characteristics, quality and results.
The results showed low predictive accuracy overall. For preeclampsia, the best predictor was PlGF; LR + 4.01 (3.74, 4.28), LR-(0.67, 0.64, 0.69). The predictive value of serum markers for early preeclampsia was better than that of late preeclampsia. For SGA the best predictor was PP13; LR+ 3.70 (3.39, 4.03), LR- 0.70 (0.67, 0.73). For preterm delivery, the best predictor was PP13; LR+ 4.16 (2.72, 5.61), LR- 0.56 (0.45, 0.67).
First trimester screening analytes have low predictive accuracy for pre-eclampsia, small for gestational age and preterm delivery. However, the predict value of first trimester analytes is not worse than that of the second trimester markers.
... This is an increase in successful linkages of 4% compared with the linkage of mother's laboratory data to the perinatal database. 29 The addition of one more piece of personal information, hospital of birth, available on NBS data led to this increase in linkage rates. The processes of record linkage and data analysis are separated; therefore, researchers only have access to de-identified data and study participants' privacy is ensured. ...
Studies examining the relationship between maternal and infant thyroid parameters have shown conflicting results. Record linkage provides an opportunity to examine the association between maternal and infant thyroid-stimulating hormone (TSH) levels. Our aim was to demonstrate the feasibility of record linkage of newborn screening (NBS), laboratory and birth databases for research by investigating the association between maternal and newborn TSH levels.
The records of 2802 women with first trimester serum TSH concentrations were linked with population-based birth data and NBS data containing infant TSH levels. Association between moderately high neonatal TSH levels (>5 mIU/L) and maternal and infant characteristics was evaluated. The correlation and association between maternal and infant TSH levels were assessed using Pearson's correlation coefficient and multivariable linear regression, respectively.
Of maternal and birth records, 99.3% linked with an NBS record. Mother's country of birth, gestational age (>41 weeks) and lower birthweight were associated with neonatal TSH levels >5 mIU/L. Neonatal and maternal first trimester TSH levels were not correlated, although statistically significant (r = 0.05, P = 0.008). The association between neonatal TSH and maternal TSH, after adjusting for maternal age, gestational age and age at NBS testing, was also small (b = 0.039, P = 0.009).
Record linkage is a feasible and cost-efficient way to investigate the association between maternal factors and neonatal hormone levels. First trimester maternal thyroid levels are not correlated with neonatal TSH levels. This method of outcome assessment can be used for future research examining long-term outcomes for infants with different NBS results.
© 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
... Given that countryrelated heterogeneity exists in methadone treatment (e.g., program content, coverage rate and methadone dose) and treatment seekers (e.g., age, educational attainment, racial composition and addiction severity) (Baewert et al., 2012;Unger et al., 2010), the results may not be directly generalized to Asian countries. Recently, record linkage, an approach that connects records for the same individual across different data sources, has been used to study adverse obstetric outcomes related to illegal drug uses by bringing together the drug-related hospital admission and birth records (Burns et al., 2006Lain, Algert, Tasevski, Morris, & Roberts, 2009). However, these studies often focus on outcome-specific excessive risks, thus obscuring the association between the overall risk of adverse obstetric outcomes and its explanatory factors. ...
... In Australia unit record data from multiple datasets cannot be produced because unique identifiers are not available for record linkage. Therefore, probabilistic linkage methods are used [7,8] . This involves a complex process of blocking and matching combinations of selected variables (such as name, date of birth, address and hospital ) using record-linkage software [9]. ...
To assess the accuracy of first trimester soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in predicting pregnancy hypertension and pre-eclampsia; and compare with the accuracy of routinely collected maternal and clinical risk factors.
In this population-based cohort study, serum sFlt-1 and PlGF levels were measured in first trimester in 2,681 women with singleton pregnancies in New South Wales, Australia.
Prediction of pregnancy hypertension and pre-eclampsia.
There were 213 (7.9%) women with pregnancy hypertension, including 68 (2.5%) with pre-eclampsia. The area under the curve (AUC) for both sFlt-1 and PlGF was not different from chance, but combined was 0.55 (P=0.005). Parity and previous diagnosed hypertension had better predictive accuracy than serum biomarkers (AUC=0.64, P<0.001) and the predictive accuracy for all maternal and clinical information was fair (AUC=0.70, P<0.001 for pregnancy hypertension and AUC=0.74, P<0.001 for pre-eclampsia). Adding sFlt-1 and PlGF to maternal risk factors did not improve the ability of the models to predict pregnancy hypertension or pre-eclampsia.
Maternal first trimester serum concentrations of sFlt-1 and PlGF do not predict hypertensive disorders in pregnancy any better than routinely collected clinical and maternal risk factor information. Screening for sFlt-1 and PlGF levels in early pregnancy would not identify those pregnancies at-risk.
Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.
... In Australia unit record data from multiple datasets cannot be produced because unique identifiers are not available for record linkage. Therefore, probabilistic linkage methods are used [7,8]. This involves a complex process of blocking and matching combinations of selected variables (such as name, date of birth, address and hospital) using record-linkage software [9]. ...
... This involves a complex process of blocking and matching combinations of selected variables (such as name, date of birth, address and hospital) using record-linkage software [9]. The validity of the probabilistic record linkage is extremely high with less than 1% of records having an incorrect match [7][8][9]. Record linkage was conducted by The NSW Centre for Health Record Linkage (CHeReL) and identifying information are removed before the data are sent to researchers. The CHeReL assesses the linkage quality for each study, and for this study there were <5/1000 missed links and <2/1000 false positive links. ...
Objective
To assess the accuracy of first trimester soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in predicting pregnancy hypertension and pre-eclampsia; and compare with the accuracy of routinely collected maternal and clinical risk factors.
Study design
In this population-based cohort study, serum sFlt-1 and PlGF levels were measured in first trimester in 2,681 women with singleton pregnancies in New South Wales, Australia.
Main outcome measures
Prediction of pregnancy hypertension and pre-eclampsia.
Results
There were 213 (7.9%) women with pregnancy hypertension, including 68 (2.5%) with pre-eclampsia. The area under the curve (AUC) for both sFlt-1 and PlGF was not different from chance, but combined was 0.55 (P = 0.005). Parity and previous diagnosed hypertension had better predictive accuracy than serum biomarkers (AUC = 0.64, P < 0.001) and the predictive accuracy for all maternal and clinical information was fair (AUC = 0.70, P < 0.001 for pregnancy hypertension and AUC = 0.74, P < 0.001 for pre-eclampsia). Adding sFlt-1 and PlGF to maternal risk factors did not improve the ability of the models to predict pregnancy hypertension or pre-eclampsia.
Conclusions
Maternal first trimester serum concentrations of sFlt-1 and PlGF do not predict hypertensive disorders in pregnancy any better than routinely collected clinical and maternal risk factor information. Screening for sFlt-1 and PlGF levels in early pregnancy would not identify those pregnancies at-risk.
... 5,6 Data linkage allows enhanced utilization of PHDS for a range of research opportunities, including longitudinal studies, 7 the collection of outcome and cost data for randomized controlled trials, 8 and more recently the linkage of PHDS with laboratory data to find biomarkers of adverse outcomes. 9 International population data collected for billing services, such as hospital discharge data, or for state and federal registries, such as birth and death certificate data, may be available and accessible but uncertainty remains over their accuracy and completeness. ...
Administrative or population health datasets (PHDS) are increasingly being used for research related to maternal and infant health. However, the accuracy and completeness of the information in the PHDS is important to ensure validity of the results of this research.
To compile and review studies that validate the reporting of conditions and procedures related to pregnancy, childbirth, and newborns and provide a tool of reference for researchers.
A systematic search was conducted of Medline and EMBASE databases to find studies that validated routinely collected datasets containing diagnoses and procedures related to pregnancy, childbirth, and newborns. To be included datasets had to be validated against a gold standard, such as review of medical records, maternal interview or survey, specialized register, or laboratory data. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and/or κ statistic for each diagnosis or procedure code were calculated.
Forty-three validation studies were included. Under-enumeration was common, with the level of ascertainment increasing as time from diagnosis/procedure to birth decreased. Most conditions and procedures had high specificities indicating few false positives, and procedures were more accurately reported than diagnoses. Hospital discharge data were generally more accurate than birth data, however identifying cases from more than 1 dataset further increased ascertainment.
This comprehensive collection of validation studies summarizing the quality of perinatal population data will be an invaluable resource to all researchers working with PHDS.
... There is some evidence that in pregnancies delivering preterm the endocervical length is reduced at 11-13 weeks (Greco et al., 2011). Several studies have also investigated the potential value of uterine artery pulsatility index (PI) and maternal serum concentrations of pregnancy-associated plasma protein-A (PAPP-A), free β-human chorionic gonadotrophin (β-hCG), PlGF, placental protein 13 (PP13), a disintegrin and metalloprotease 12 (ADAM12), inhibin-A and activin-A and reported contradictory results (Strigini et al., 1995;Germain et al., 1999;Smith et al., 2002Smith et al., , 2007Tul et al., 2003;Agarwal et al., 2004;Cobian-Sanchez et al., 2004;Dugoff et al., 2004Dugoff et al., , 2005Krantz et al., 2004;Spencer et al., 2005Spencer et al., , 2008Farina et al., 2006;Fonseca et al., 2006;Chafetz et al., 2007;Cowans et al., 2007Cowans et al., , 2008Soares et al., 2007;Poon et al., 2008Poon et al., , 2009Chaiworapongsa et al., 2009;Lain et al., 2009;Goetzinger et al., 2010;Huang et al., 2010). ...
... We found a small decrease in serum PAPP-A at 11-13 weeks in pregnancies that subsequently deliver spontaneously before 34 weeks but no significant differences in the levels of serum free β-hCG, PLGF, PP13, ADAM12, activin-A or inhibin-A. These results are compatible with findings in previous studies investigating maternal levels of these biomarkers at 11-13 weeks in the prediction of preterm delivery (Morssink et al., 1998;Ong et al., 2000;Smith et al., 2002Smith et al., , 2007Tul et al., 2003;Dugoff et al., 2004;Krantz et al., 2004;Spencer et al., 2005Spencer et al., , 2008Cowans et al., 2007Cowans et al., , 2008She et al., 2007;Poon et al., 2008Poon et al., , 2009Lain et al., 2009;Huang et al., 2010). However, one study of 46 women with subsequent spontaneous delivery before 37 weeks reported significantly increased serum PP13 at 9-12 weeks (Chafetz et al., 2007). ...
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.
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.
