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Jenny E Myers,
Robin Tuytten,
Grégoire Thomas,
Wouter Laroy,
Koen Kas,
Griet Vanpoucke,
Claire T Roberts,
Louise C Kenny,
Nigel A B Simpson,
Philip N Baker, Robyn A North
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ABSTRACT: Preeclampsia, a hypertensive pregnancy complication, is largely unpredictable in healthy nulliparous pregnant women. Accurate preeclampsia prediction in this population would transform antenatal care. To identify novel protein markers relevant to the prediction of preeclampsia, a 3-step mass spectrometric work flow was applied. On selection of candidate biomarkers, mostly from an unbiased discovery experiment (19 women), targeted quantitation was used to verify and validate candidate biomarkers in 2 independent cohorts from the SCOPE (SCreening fOr Pregnancy Endpoints) study. Candidate proteins were measured in plasma specimens collected at 19 to 21 weeks' gestation from 100 women who later developed preeclampsia and 200 women without preeclampsia recruited from Australia and New Zealand. Protein levels (n=25), age, and blood pressure were then analyzed using logistic regression to identify multimarker models (maximum 6 markers) that met predefined criteria: sensitivity ≥50% at 20% positive predictive value. These 44 algorithms were then tested in an independent European cohort (n=300) yielding 8 validated models. These 8 models detected 50% to 56% of preeclampsia cases in the training and validation sets; the detection rate for preterm preeclampsia cases was 80%. Validated models combine insulin-like growth factor acid labile subunit and soluble endoglin, supplemented with maximally 4 markers of placental growth factor, serine peptidase inhibitor Kunitz type 1, melanoma cell adhesion molecule, selenoprotein P, and blood pressure. Predictive performances were maintained when exchanging mass spectrometry measurements with ELISA measurements for insulin-like growth factor acid labile subunit. In conclusion, we demonstrated that biomarker combinations centered on insulin-like growth factor acid labile subunit have the potential to predict preeclampsia in healthy nulliparous women.
Hypertension 04/2013; · 6.21 Impact Factor
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ABSTRACT: Background: Large-for-gestational-age (LGA) or macrosomic infants are associated with adverse maternal and neonatal outcomes. It is unclear if these associations are stronger using customised birthweight centiles. We compared outcomes between term infants defined macrosomic by birthweight >4000 g (Macro(4000) ) or LGA by population centiles (LGA(pop) ) with those defined LGA by customised centiles (LGA(cust) ). Methods: This is a prospective cohort study of 2668 term nulliparous women recruited into the Screening for Pregnancy Endpoints (SCOPE) study centres in Auckland, New Zealand and Adelaide, Australia. Maternal (caesarean delivery, postpartum haemorrhage) and infant (severe neonatal morbidity/mortality and admission to neonatal intensive care) outcomes in Macro(4000) and LGA groups were compared with appropriate-for-gestational-age infants by customised centiles using logistic regression. Results: Customised centiles defined fewer infants as LGA (10.3% LGA(cust) , 14.8% Macro(4000) , 11.2% LGA(pop) ). However customised centiles showed stronger association with adverse outcomes. Pre-labour and intrapartum caesarean section were increased twofold in LGA(cust) pregnancies, including those that were not Macro(4000) or LGA(pop) . Postpartum haemorrhage was increased twofold in mothers of LGA(cust) infants only when infants were also LGA(pop) . Severe neonatal morbidity/mortality or admission to neonatal intensive care was increased twofold in LGA(cust) who were also either Macro(4000) or LGA(pop) . Importantly 52.3% of Macro(4000) and 25.5% of LGA(pop) infants were AGA(cust) and not at increased risk of most adverse maternal or neonatal outcomes. Conclusions: The use of customised centiles are more strongly associated with adverse birth outcomes and its use should be considered in the definition of LGA.
Paediatric and Perinatal Epidemiology 11/2012; 26(6):543-552. · 2.31 Impact Factor
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ABSTRACT: Objective. To describe patterns of vaginal bleeding in the first 20 weeks of pregnancy and evaluate the association between patterns of bleeding and risk of subsequent pre-eclampsia in nulliparous women. Design. Cohort study. Setting. Participating centres of the Screening for Pregnancy Endpoints (SCOPE) study in Auckland (New Zealand), Adelaide (Australia), Manchester and London (UK) and Cork (Ireland). Population. Healthy nulliparous women (n= 3431). Methods. Logistic regression was used to assess the association between bleeding characteristics and pre-eclampsia while controlling for known determinants of pre-eclampsia. Main outcome measures. Preeclampsia, defined as gestational hypertension with proteinuria or any multi-system complication of preeclampsia. Four bleeding variables were evaluated: any bleeding during the first 20 weeks; maximal bleeding intensity; duration of bleeding; and number of bleeding episodes. Results. Of the 3431 women enrolled, 780 (23%) experienced vaginal bleeding during the first 20 weeks of pregnancy. Risk of pre-eclampsia was not associated with the presence or absence of bleeding (adjusted odds ratio (ORa) 0.96, 95% confidence interval (95% CI) 0.67-1.38). Analyses confined to women with vaginal bleeding showed that any bleeding episode of five or more consecutive days, compared with shorter episodes, increased risk of pre-eclampsia approximately twofold (ORa 2.15, 95% CI 1.01-4.57), as did multiple compared with single episodes of bleeding (ORa 2.33, 95% CI 1.16-4.67). Conclusions. Bleeding is a common complication during the first 20 weeks of nulliparous pregnancy, and the presence or absence of vaginal bleeding is not a determinant of subsequent pre-eclampsia. Among women with vaginal bleeding, consideration of the bleeding pattern, in terms of intensity, duration and frequency, appears to be informative with respect to pre-eclampsia risk.
Acta Obstetricia Et Gynecologica Scandinavica 07/2012; · 1.77 Impact Factor
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ABSTRACT: BACKGROUND: Two-dimensional polyacrylamide gel electrophoresis (2D PAGE) is commonly used to identify differentially expressed proteins under two or more experimental or observational conditions. Wu et al (2009) developed a univariate probabilistic model which was used to identify differential expression between Case and Control groups, by applying a Likelihood Ratio Test (LRT) to each protein on a 2D PAGE. In contrast to commonly used statistical approaches, this model takes into account the two possible causes of missing values in 2D PAGE: either (1) the non-expression of a protein; or (2) a level of expression that falls below the limit of detection. RESULTS: We develop a global Bayesian model which extends the previously described model. Unlike the univariate approach, the model reported here is able treat all differentially expressed proteins simultaneously. Whereas each protein is modelled by the univariate likelihood function previously described, several global distributions are used to model the underlying relationship between the parameters associated with individual proteins. These global distributions are able to combine information from each protein to give more accurate estimates of the true parameters. In our implementation of the procedure, all parameters are recovered by Markov chain Monte Carlo (MCMC) integration. The 95% highest posterior density (HPD) intervals for the marginal posterior distributions are used to determine whether differences in protein expression are due to differences in mean expression intensities, and/or differences in the probabilities of expression. CONCLUSIONS: Simulation analyses showed that the global model is able to accurately recover the underlying global distributions, and identify more differentially expressed proteins than the simple application of a LRT. Additionally, simulations also indicate that the probability of incorrectly identifying a protein as differentially expressed (i.e., the False Discovery Rate) is very low. The source code is available at https://github.com/stevenhwu/BIDE-2D.
BMC Bioinformatics 06/2012; 13(1):137. · 2.75 Impact Factor
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ABSTRACT: Obesity is associated with an increased level of inflammation. Interactions between inflammatory and angiogenic pathways are implicated in the major pregnancy disorders. The aim of this study was to investigate whether functional polymorphisms in angiogenesis-regulating genes (VEGFA rs699947, VEGFA rs3025039, KDR rs2071559 and ANGPT1 rs2507800) interact with the maternal BMI to modify the risk of a spontaneous preterm birth (sPTB). We conducted a nested case-control study of 1190 nulliparous Caucasian women (107 sPTBs and 1083 controls). Spontaneous PTB was defined as spontaneous preterm labour or a preterm premature rupture of membranes resulting in a preterm birth at <37 weeks of gestation. DNA was extracted from the peripheral blood and genotyped using the Sequenom MassARRAY system. Among overweight or obese women (BMI ≥25), the VEGFA rs699947 AA genotype was associated with a higher risk of sPTBs [odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.4-4.6, P = 0.001] and a significant interaction between the BMI and the polymorphism was detected (OR = 4.2, 95% CI: 1.7-10.9, P = 0.003). Among women with a BMI <25, ANGPT1 rs2507800 AA genotype was associated with a higher risk of sPTB (OR = 2.3, 95% CI: 1.2-4.4, P= 0.02) and a significant interaction between BMI and the polymorphism was detected (OR = 3.3, 95% CI: 1.1-9.3, P = 0.02). All results remained significant after adjusting for potential confounding factors. The maternal BMI interacts with angiogenesis-regulating gene polymorphisms to modify the risk of sPTBs.
Molecular Human Reproduction 04/2012; 18(9):459-65. · 3.85 Impact Factor
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ABSTRACT: Antepartum haemorrhage of unknown origin (APHUO) is associated with preterm birth and perinatal mortality.
To determine whether smoking beyond the first trimester of pregnancy was an independent risk factor for APHUO.
Rates of APHUO were compared between non-smokers and smokers, and non-smokers and ceased smokers. Participants were healthy nulliparous women recruited to the Screening for Pregnancy Endpoints (SCOPE) prospective cohort study in New Zealand, Australia, Ireland and United Kingdom. Logistic regression was used to compare adjusted odds ratio, 95% confidence intervals (OR, 95% CI) of APHUO between continued smokers and non-smokers, adjusting for possible confounders.
Of the 3513 participants, 77.9% (n = 2737) were non-smokers, 10.6% (n = 371) ceased in the first trimester and 11.5% (n = 405) continued smoking beyond the first trimester. APHUO rates were higher in smokers than nonsmokers (7.4%, n = 30 vs 4.5%, n = 122; P = 0.01), but there was no difference between ceased smokers and nonsmokers (4.3%, n = 16 vs 4.5%, n = 122; P = 0.90). Smoking was no longer significantly associated with APHUO after adjustment for confounders (adjusted OR = 1.28, 95% CI 0.76–2.14), but vaginal bleeding in early pregnancy (adjusted OR = 2.98, 95% CI 2.12–4.18) and overweight/obesity (adjusted OR = 1.43, 95% CI 1.02–1.99) were independent risk factors. First trimester folic acid use was associated with a reduced risk (adjusted OR = 0.44, 95% CI 0.25–0.77).
Smoking is not an independent risk factor for APHUO after adjustment for confounders, but other risk and protective factors have been identified.
Australian and New Zealand Journal of Obstetrics and Gynaecology 04/2012; 52(2):161-6. · 1.24 Impact Factor
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ABSTRACT: In our search for early biomarkers for the pregnancy complicationssmall for gestational age (SGA) and preeclampsia (PE) we analysed plasma from 19-21 weeks gestation in women recruited into the SCOPE study, a prospective cohort of nulliparous women, by differential in gel electrophoresis (DIGE). DIGE revealed the differential expression of clusterin levels and its isoforms in top6-depleted plasma of women who delivered an SGA infant but remained normotensive (SGA-NT; N = 8) compared to healthy women with an uncomplicated pregnancy outcome (Controls, N = 8). Immunosorbent enzyme-linked assay (ELISA) showed that compared to plasma clusterin levels from healthy controls [71.1 (SD 12.4) µg/mL, n = 39], clusterin was decreased in SGA-NT [58.3 (SD 11.7), N = 20, P < 0.0001], increased in women with SGA and PE [81.5 (SD 14.8), N = 20, P < 0.01], but similar in PE alone [71.2 (SD 9.4)g/ml, P = 1.0]. Screening for clusterin levels and/or its different isoformsmay be useful in mid-pregnancy to identify women who subsequently develop SGA but remain normotensive or who develop preeclampsia with SGA.
Reproductive sciences (Thousand Oaks, Calif.) 02/2012; 19(6):650-7. · 2.31 Impact Factor
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ABSTRACT: To identify risk factors for spontaneous preterm birth (birth <37 weeks gestation) with intact membranes (SPTB-IM) and SPTB after prelabour rupture of the membranes (SPTB-PPROM) for nulliparous pregnant women.
Prospective international multicentre cohort.
3234 healthy nulliparous women with a singleton pregnancy, follow up was complete in 3184 of participants (98.5%).
Of the 3184 women, 156 (4.9%) had their pregnancy complicated by SPTB; 96 (3.0%) and 60 (1.9%) in the SPTB-IM and SPTB-PPROM categories, respectively. Independent risk factors for SPTB-IM were shorter cervical length, abnormal uterine Doppler flow, use of marijuana pre-pregnancy, lack of overall feeling of well being, being of Caucasian ethnicity, having a mother with diabetes and/or a history of preeclampsia, and a family history of low birth weight babies. Independent risk factors for SPTB-PPROM were shorter cervical length, short stature, participant's not being the first born in the family, longer time to conceive, not waking up at night, hormonal fertility treatment (excluding clomiphene), mild hypertension, family history of recurrent gestational diabetes, and maternal family history of any miscarriage (risk reduction). Low BMI (<20) nearly doubled the risk for SPTB-PPROM (odds ratio 2.64; 95% CI 1.07-6.51). The area under the receiver operating characteristics curve (AUC), after internal validation, was 0.69 for SPTB-IM and 0.79 for SPTB-PPROM.
The ability to predict PTB in healthy nulliparous women using clinical characteristics is modest. The dissimilarity of risk factors for SPTB-IM compared with SPTB-PPROM indicates different pathophysiological pathways underlie these distinct phenotypes.
ACTR.org.au ACTRN12607000551493.
PLoS ONE 01/2012; 7(7):e39154. · 4.09 Impact Factor
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ABSTRACT: Pregnancies complicated by pre-eclampsia and small-for-gestational-age (SGA) infants demonstrate impaired placental vascular remodelling. Angiopoietin-1 (ANG-1) is an angiogenic growth factor which regulates vascular integrity and remodelling. The TT genotype of angiopoietin 1 (ANGPT1) rs2507800 polymorphism has been associated with increased plasma ANG-1 levels compared with the AA genotype. We aimed to investigate the association between ANGPT1 rs2507800 polymorphism and pregnancies complicated by gestational hypertensive disorders and SGA infants. We also aimed to investigate whether the polymorphism was associated with abnormal uterine artery Doppler as a surrogate marker of impaired placental vascular remodelling. Genotyping data of 1361 nulliparous pregnant women, 1226 partners and 1190 infants were analysed. The prevalence of ANGPT1 rs2507800 TT genotype was reduced in women with pre-eclampsia [P = 0.01, adjusted odds ratio (aOR), 0.5; 95% confidence interval (CI), 0.3-0.9], hypertensive SGA (P = 0.04, aOR, 0.5; 95% CI, 0.2-0.9) and SGA with abnormal uterine artery Doppler (P = 0.009, aOR, 0.4. 95% CI, 0.2-0.8) compared with women with uncomplicated pregnancy. The prevalence of maternal ANGPT1 rs2507800 TT genotype was reduced in women with increased uterine artery resistance index (P = 0.03, aOR, 0.7; 95% CI, 0.5-0.9) and bilateral notching of the uterine arteries (P = 0.004, aOR, 0.6; 95% CI, 0.4-0.9). These results remained significant after correcting for multiple testing. Maternal ANGPT1 rs2507800 TT genotype is associated with a reduced risk for pre-eclampsia, hypertensive SGA and abnormal uterine artery Doppler. These findings suggest that the TT genotype may protect against these pregnancy disorders by increasing ANG-1 production at the maternal-fetal interface. The ANGPT1 rs2507800 polymorphism may have a potential role in screening women to predict the risk of these pregnancy complications. TRIAL REGISTRY NAME: Screening nulliparous women to identify the combinations of clinical risk factors and/or biomarkers required to predict pre-eclampsia, SGA babies and spontaneous preterm birth.
Molecular Human Reproduction 12/2011; 18(6):325-32. · 3.85 Impact Factor
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ABSTRACT: To examine whether single-nucleotide polymorphisms (SNPs) in VEGFA (-2578 C/A and +936 C/T) associate with small-for-gestational-age (SGA) pregnancies and to identify their effects on first-trimester placental VEGFA expression.
Multicenter prospective cohort study.
Adelaide, Australia, and Auckland, New Zealand.
A total of 3234 nulliparous pregnant women, their partners, and their infants.
The SNPs in the parent-infant trios and first-trimester placentae (n = 74) were genotyped. Placental VEGFA messenger RNA expression was determined by quantitative reverse transcription-polymerase chain reaction. Small for gestational age was defined as a birth weight less than the 10th customized birth weight percentile adjusted for maternal height, weight, parity, and ethnicity and for gestational age at delivery and infant sex. Uterine and umbilical artery Doppler was performed at 20 weeks' gestation, and resistance indices greater than the 90th percentile were considered abnormal.
Of 2123 pregnancies, 1176 (55.4%) were uncomplicated and 216 (10.2%) had SGA infants. Neonatal VEGFA +936 C/T SNP associates with SGA (adjusted odds ratio [aOR], 1.6; 95% CI, 1.0-2.3), SGA with abnormal Doppler findings (aOR, 3.5; 95% CI, 1.8-7.1), lower birth weight (P = .006), customized birth weight percentile (P = .049), and abnormal uterine artery Doppler findings (OR, 2.5; 95% CI, 1.2-5.4). Maternal VEGFA +936 C/T associates with abnormal umbilical artery Doppler findings (OR, 1.5; 95% CI, 1.1-2.2). VEGFA +936 CT+TT first-trimester placentae have 36% lower VEGFA messenger RNA expression compared with CC (P = .045).
Neonatal VEGFA +936 C/T associates with SGA, and the association is stronger for SGA with abnormal uterine or umbilical artery Doppler findings. The SNP also associates with reduced first-trimester placental VEGFA expression, suggesting that it may have a role in the pathogenesis of SGA. Trial Registration clinicaltrials.gov Identifier: ACTRN12607000551493.
Archives of pediatrics & adolescent medicine 12/2011; 165(12):1123-30. · 3.73 Impact Factor
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Richard P Horgan,
David I Broadhurst,
Sarah K Walsh,
Warwick B Dunn,
Marie Brown,
Claire T Roberts, Robyn A North,
Lesley M McCowan,
Douglas B Kell,
Philip N Baker,
Louise C Kenny
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ABSTRACT: Being born small for gestational age (SGA) confers increased risks of perinatal morbidity and mortality and increases the risk of cardiovascular complications and diabetes in later life. Accumulating evidence suggests that the etiology of SGA is usually associated with poor placental vascular development in early pregnancy. We examined metabolomic profiles using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) in three independent studies: (a) venous cord plasma from normal and SGA babies, (b) plasma from a rat model of placental insufficiency and controls, and (c) early pregnancy peripheral plasma samples from women who subsequently delivered a SGA baby and controls. Multivariate analysis by cross-validated Partial Least Squares Discriminant Analysis (PLS-DA) of all 3 studies showed a comprehensive and similar disruption of plasma metabolism. A multivariate predictive model combining 19 metabolites produced by a Genetic Algorithm-based search program gave an Odds Ratio for developing SGA of 44, with an area under the Receiver Operator Characteristic curve of 0.9. Sphingolipids, phospholipids, carnitines, and fatty acids were among this panel of metabolites. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of SGA offers insight into disease pathogenesis and offers the promise of a robust presymptomatic screening test.
Journal of Proteome Research 06/2011; 10(8):3660-73. · 5.11 Impact Factor
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ABSTRACT: To estimate in a cohort of nulliparous women in labor at term whether cesarean delivery rates are increased in first and second stages of labor in overweight and obese women and whether being overweight or obese is an independent risk factor for cesarean delivery.
Nulliparous women recruited to the prospective Screening for Pregnancy Endpoints study who went into labor after 37 weeks of gestation were categorized according to ethnicity-specific body mass index (BMI) criteria as normal, overweight, or obese. Normal BMI was the referent. Multivariable analysis, adjusting for known confounders for obesity and cesarean delivery, was performed to estimate if being overweight or obese was associated with an increased risk of cesarean in labor (all cesarean deliveries and in first stage of labor).
Of 2,629 participants, 1,416 (54%) had normal BMIs, 773 (29%) were overweight, and 440 (17%) were obese. First-stage cesarean delivery was increased in overweight (n=149 [19%]) and obese (n=137 [31%]) women compared with normal-weight women (n=181 [13%; P<.001), whereas second-stage cesarean delivery was similar (normal BMI 76 [6.2%], overweight 45 [7.2%], obese 23 [7.6%], P=.87). Being overweight or obese was an independent risk factor for all cesarean deliveries in labor with adjusted odds ratio (OR) of 1.34 (95% confidence interval [CI] 1.07-1.67) and 2.51 (95% CI 1.94-3.25), respectively. Similarly, being overweight (adjusted OR 1.39; 95% CI 1.09-1.79) or obese (adjusted OR 2.89; 95% CI 2.19-3.80) was associated with increased cesarean delivery during the first stage. Risks of cesarean delivery were similar regardless of whether ethnicity-specific or World Health Organization (WHO) BMI criteria were used.
Among nulliparous women in labor at term, being overweight or obese by either WHO or ethnicity-specific BMI criteria is an independent risk factor for cesarean delivery in the first stage but not the second stage of labor.
Australian New Zealand Clinical Trials Registry, www.anzctr.org.au, ACTRN12607000551493.
Obstetrics and Gynecology 06/2011; 117(6):1315-22. · 4.73 Impact Factor
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David M Carty,
Justyna Siwy,
Janet E Brennand,
Petra Zürbig,
William Mullen,
Julia Franke,
James W McCulloch,
Claire T Roberts, Robyn A North,
Lucy C Chappell,
Harald Mischak,
Lucilla Poston,
Anna F Dominiczak,
Christian Delles
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ABSTRACT: Preeclampsia is a major determinant of fetal and maternal morbidity and mortality. We used a proteomic strategy to identify urinary biomarkers that predict preeclampsia before the onset of disease. We prospectively collected urine samples from women throughout pregnancy. Samples from gestational weeks 12 to 16 (n=45), 20 (n=50), and 28 (n=18) from women who subsequently had preeclampsia develop were matched to controls (n=86, n=49, and n=17, respectively). We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry. Disease-specific peptide patterns were generated using support vector machine-based software. Candidate biomarkers were sequenced by liquid chromatography-tandem mass spectrometry. From comparison with nonpregnant controls, we defined a panel of 284 pregnancy-specific proteomic biomarkers. Subsequently, we developed a model of 50 biomarkers from specimens obtained at week 28 that was associated with future preeclampsia (classification factor in cases, 1.032 ± 0.411 vs controls, -1.038 ± 0.432; P<0.001). Classification factor increased markedly from week 12 to 16 to 28 in women who subsequently had preeclampsia develop (n=16; from -0.392 ± 0.383 to 1.070 ± 0.383; P<0.001) and decreased slightly in controls (n=16; from -0.647 ± 0.437 to -1.024 ± 0.433; P=0.043). Among the biomarkers are fibrinogen alpha chain, collagen alpha chain, and uromodulin fragments. The markers appear to predict preeclampsia at gestational week 28 with good confidence but not reliably at earlier time points (weeks 12-16 and 20). After prospective validation in other cohorts, these markers may contribute to better prediction, monitoring, and accurate diagnosis of preeclampsia.
Hypertension 03/2011; 57(3):561-9. · 6.21 Impact Factor
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ABSTRACT: Placental derived vasculogenic/angiogenic substances in maternal blood are dysregulated in pre-eclampsia. We hypothesized that CXCL12, a chemokine with vasculogenic actions, is amongst such molecules.
CXCL12, CXCL16, CXCR4, and CXCR6 immunolocalization in placental tissue was analyzed in pre-eclampsia (n=8) in comparison to controls (n=8). CXCL12, measured by ELISA in blood, in women diagnosed with pre-eclampsia (n=14) and prior to the development of pre-eclampsia (at 20 weeks' gestation, n=20) was compared with CXCL12 concentrations in gestation-matched, healthy control subjects (n=34).
In placental tissue, syncytiotrophoblast staining for CXCL12 was increased in pre-eclampsia. Maternal serum CXCL12 was increased in pre-eclampsia [2000 (SD 402) vs 1484 (SD 261)pg/ml, P=0.01] but not in plasma obtained at 20 weeks of gestation prior to the onset of pre-eclampsia [1183 (SD 336) vs 1036 (SD 144)pg/ml, P=0.09].
Our data suggest that the syncytiotrophoblast contributes to a pre-eclampsia-associated increase in CXCL12 levels in maternal blood. These findings support the hypothesis that an imbalance of angiogenic factors contributes to the pathogenesis of pre-eclampsia.
European journal of obstetrics, gynecology, and reproductive biology 03/2011; 157(1):32-7. · 1.97 Impact Factor
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ABSTRACT: To investigate the association between hyperemesis gravidarum and altered cognitive, behavioural and emotional well-being in pregnancy.
The study cohort consisted of 3423 nulliparous women recruited in the Screening for Pregnancy Endpoints (SCOPE) study performed in Auckland, New Zealand; Adelaide, Australia; Cork, Ireland; Manchester and London, United Kingdom between November 2004 and August 2008. Women were interviewed at 15±1 weeks' gestation and at 20±1weeks' gestation. Women with a diagnosis of hyperemesis gravidarum (HG) were compared with women who did not have a diagnosis of HG. Main outcome measures included the Short form State- Trait Anxiety Inventory (STAI) score (range 6-24), Perceived Stress Scale score (PSS, range 0-30), Edinburgh Postnatal Depression Scale (EPDS) score (range 0-30 or categories a-c) and behavioural responses to pregnancy score (limiting/resting [range 0-20] and all-or-nothing [range 0-28]).
During the study period 164 women suffered from HG prior to their 15 week interview. Women with HG had significantly higher mean STAI, PSS, EPDS and limiting response to pregnancy scores compared to women without HG. These differences were observed at both 15±1 and 20±1 weeks' of gestation. The magnitude of these differences was greater in women with severe HG compared to all women with HG. Women with severe HG had an increased risk of having a spontaneous preterm birth compared with women without HG (adjusted OR 2.6 [95% C.I. 1.2, 5.7]).
This is the first large prospective study on women with HG. Women with HG, particularly severe HG, are at increased risk of cognitive, behavioural and emotional dysfunction in pregnancy. Women with severe HG had a higher rate of spontaneous preterm birth compared to women without HG. Further research is required to determine whether the provision of emotional support for women with HG is beneficial.
PLoS ONE 01/2011; 6(11):e27678. · 4.09 Impact Factor
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Paul T Seed,
Lucy C Chappell,
Michael A Black,
Katrina K Poppe,
Yuan-Chun Hwang,
Nikola Kasabov,
Lesley McCowan,
Andrew H Shennan,
Steven H Wu,
Lucilla Poston, Robyn A North
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ABSTRACT: To develop clinical risk tools for preeclampsia and small for gestational age (SGA) in high-risk women.
Individual risk scores based on clinical risk factors were calculated using logistic regression and validated in 1687 women with obesity in first pregnancy, chronic hypertension, or previous preeclampsia.
The risk of preeclampsia varied from 7% in obese primiparae without hypertension to 30% when previous preeclampsia and chronic hypertension occurred together. A prediction model incorporating these risk factors had a sensitivity of 48 and 89% for preeclampsia delivered <34 weeks' gestation.
Multiple clinical risk factors increase the risk of preeclampsia and SGA.
Hypertension in Pregnancy 01/2011; 30(1):58-73. · 1.69 Impact Factor
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Robyn A North,
Lesley M E McCowan,
Gustaaf A Dekker,
Lucilla Poston,
Eliza H Y Chan,
Alistair W Stewart,
Michael A Black,
Rennae S Taylor,
James J Walker,
Philip N Baker,
Louise C Kenny
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ABSTRACT: To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated.
Prospective multicentre cohort.
Five centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland.
3572 "healthy" nulliparous women with a singleton pregnancy from a large international study; data on pregnancy outcome were available for 3529 (99%).
Pre-eclampsia defined as ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg, or both, on at least two occasions four hours apart after 20 weeks' gestation but before the onset of labour, or postpartum, with either proteinuria or any multisystem complication. Preterm pre-eclampsia was defined as women with pre-eclampsia delivered before 37(+0) weeks' gestation. In the stepwise logistic regression the comparison group was women without pre-eclampsia.
Of the 3529 women, 186 (5.3%) developed pre-eclampsia, including 47 (1.3%) with preterm pre-eclampsia. Clinical risk factors at 14-16 weeks' gestation were age, mean arterial blood pressure, body mass index (BMI), family history of pre-eclampsia, family history of coronary heart disease, maternal birth weight, and vaginal bleeding for at least five days. Factors associated with reduced risk were a previous single miscarriage with the same partner, taking at least 12 months to conceive, high intake of fruit, cigarette smoking, and alcohol use in the first trimester. The area under the receiver operating characteristics curve (AUC), under internal validation, was 0.71. Addition of uterine artery Doppler indices did not improve performance (internal validation AUC 0.71). A framework for specialist referral was developed based on a probability of pre-eclampsia generated by the model of at least 15% or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors. Nine per cent of nulliparous women would be referred for a specialist opinion, of whom 21% would develop pre-eclampsia. The relative risk for developing pre-eclampsia and preterm pre-eclampsia in women referred to a specialist compared with standard care was 5.5 and 12.2, respectively.
The ability to predict pre-eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other populations. If validated, it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added. Trial registration ACTRN12607000551493.
BMJ (Clinical research ed.). 01/2011; 342:d1875.
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ABSTRACT: Our aims were to investigate whether men who fathered small for gestational age (SGA) infants themselves had lower birthweight, were more likely to be obese, have central adiposity and elevated blood pressure in adult life compared with men who fathered non-SGA infants. A total of 2,002 couples participating in the Screening for Pregnancy Endpoints (SCOPE) study were enrolled in early pregnancy and pregnancy outcome data collected prospectively. SGA was defined as birthweight <10th customized centile, obesity as BMI ≥30 kg/m(2), central adiposity as waist circumference >102 cm. Logistic regression was used to compare rates of obesity, and central adiposity between men who fathered SGA infants compared with those with non-SGA infants and the final model was adjusted for maternal and paternal confounders. The men who fathered an SGA infant (209 (10.4%)) themselves had lower mean birthweight (3,291 (530) g vs. 3,472 (584) g, P < 0.0001), were more likely to be obese (50 (24.8%) vs. 321 (18.3%), adjusted odds ratio (OR) 1.50, 95% confidence interval 1.05-2.16, adjusted for maternal and paternal factors) and to have central adiposity (52 (25.1%) vs. 341 (19.2%), adjusted OR 1.53, 95% confidence interval 1.06-2.20) compared with men who fathered a non-SGA infant. Elevated paternal blood pressure was not associated with SGA. In conclusion, we report a novel relationship between paternal obesity/central adiposity and birth of an SGA infant, which appears to be independent of maternal factors associated with fetal growth restriction.
Obesity 12/2010; 19(5):1035-9. · 4.28 Impact Factor
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ABSTRACT: Preeclampsia is a pregnancy-specific syndrome that causes substantial maternal and fetal morbidity and mortality. The etiology is incompletely understood, and there is no clinically useful screening test. Current metabolomic technologies have allowed the establishment of metabolic signatures of preeclampsia in early pregnancy. Here, a 2-phase discovery/validation metabolic profiling study was performed. In the discovery phase, a nested case-control study was designed, using samples obtained at 15±1 weeks' gestation from 60 women who subsequently developed preeclampsia and 60 controls taking part in the prospective Screening for Pregnancy Endpoints cohort study. Controls were proportionally population matched for age, ethnicity, and body mass index at booking. Plasma samples were analyzed using ultra performance liquid chromatography-mass spectrometry. A multivariate predictive model combining 14 metabolites gave an odds ratio for developing preeclampsia of 36 (95% CI: 12 to 108), with an area under the receiver operator characteristic curve of 0.94. These findings were then validated using an independent case-control study on plasma obtained at 15±1 weeks from 39 women who subsequently developed preeclampsia and 40 similarly matched controls from a participating center in a different country. The same 14 metabolites produced an odds ratio of 23 (95% CI: 7 to 73) with an area under receiver operator characteristic curve of 0.92. The finding of a consistent discriminatory metabolite signature in early pregnancy plasma preceding the onset of preeclampsia offers insight into disease pathogenesis and offers the tantalizing promise of a robust presymptomatic screening test.
Hypertension 10/2010; 56(4):741-9. · 6.21 Impact Factor
