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Objectives: To compare the prevalence and predictors of alcohol use in multiple cohorts., Design: Cross-cohort comparison of retrospective and prospective studies., Setting: Population-based studies in Ireland, the UK, Australia and New Zealand., Participants: 17,244 women of predominantly Caucasian origin from two Irish retrospective studies (Growing up in Ireland (GUI) and Pregnancy Risk Assessment Monitoring System Ireland (PRAMS Ireland)), and one multicentre prospective international cohort, Screening for Pregnancy Endpoints (SCOPE) study., Primary and Secondary Outcome Measures: Prevalence of alcohol use pre-pregnancy and during pregnancy across cohorts. Sociodemographic factors associated with alcohol consumption in each cohort., Results: Alcohol consumption during pregnancy in Ireland ranged from 20% in GUI to 80% in SCOPE, and from 40% to 80% in Australia, New Zealand and the UK. Levels of exposure also varied substantially among drinkers in each cohort ranging from 70% consuming more than 1-2 units/week in the first trimester in SCOPE Ireland, to 46% and 15% in the retrospective studies. Smoking during pregnancy was the most consistent predictor of gestational alcohol use in all three cohorts, and smokers were 17% more likely to drink during pregnancy in SCOPE, relative risk (RR)=1.17 (95% CI 1.12 to 1.22), 50% more likely to drink during pregnancy in GUI, RR=1.50 (95% CI 1.36 to 1.65), and 42% more likely to drink in PRAMS, RR=1.42 (95% CI 1.18 to 1.70)., Conclusions: Our data suggest that alcohol use during pregnancy is prevalent and socially pervasive in the UK, Ireland, New Zealand and Australia. New policy and interventions are required to reduce alcohol prevalence both prior to and during pregnancy. Further research on biological markers and conventions for measuring alcohol use in pregnancy is required to improve the validity and reliability of prevalence estimates., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To identify factors at 15 and 20 weeks' gestation associated with a subsequent uncomplicated pregnancy., Design: Prospective international multicentre observational cohort study., Setting: Auckland, New Zealand and Adelaide, Australia (exploration and local replication dataset) and Manchester, Leeds, and London, United Kingdom, and Cork, Republic of Ireland (external confirmation dataset)., Participants: 5628 healthy nulliparous women with a singleton pregnancy., Main Outcome Measure: Uncomplicated pregnancy, defined as a normotensive pregnancy delivered at >37 weeks' gestation, resulting in a liveborn baby not small for gestational age, and the absence of any other significant pregnancy complications. In a stepwise logistic regression the comparison group was women with a complicated pregnancy., Results: Of the 5628 women, 3452 (61.3%) had an uncomplicated pregnancy. Factors that reduced the likelihood of an uncomplicated pregnancy included increased body mass index (relative risk 0.74, 95% confidence intervals 0.65 to 0.84), misuse of drugs in the first trimester (0.90, 0.84 to 0.97), mean diastolic blood pressure (for each 5 mm Hg increase 0.92, 0.91 to 0.94), and mean systolic blood pressure (for each 5 mm Hg increase 0.95, 0.94 to 0.96). Beneficial factors were prepregnancy fruit intake at least three times daily (1.09, 1.01 to 1.18) and being in paid employment (per eight hours' increase 1.02, 1.01 to 1.04). Detrimental factors not amenable to alteration were a history of hypertension while using oral contraception, socioeconomic index, family history of any hypertensive complications in pregnancy, vaginal bleeding during pregnancy, and increasing uterine artery resistance index. Smoking in pregnancy was noted to be a detrimental factor in the initial two datasets but did not remain in the final model., Conclusions: This study identified factors associated with normal pregnancy through adoption of a novel hypothesis generating approach, which has shifted the emphasis away from adverse outcomes towards uncomplicated pregnancies. Although confirmation in other cohorts is necessary, this study implies that individually targeted lifestyle interventions (normalising maternal weight, increasing prepregnancy fruit intake, reducing blood pressure, stopping misuse of drugs) may increase the likelihood of normal pregnancy outcomes., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12607000551493.

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.

An overrepresentation of adverse pregnancy outcomes has been observed in pregnancies associated with a male fetus. We investigated the association between fetal gender and candidate biomarkers for preeclampsia. Proteins were quantified in samples taken at 20 weeks from women recruited to the SCreening fOr Pregnancy Endpoints (SCOPE) study (preeclampsia n = 150; no preeclampsia n = 450). In contrast to placental growth factor, soluble endoglin, and insulin-like growth factor acid labile subunit, levels of metallopeptidase domain 12 (ADAM12) at 20 weeks were dependent on fetal gender in pregnancies complicated by preeclampsia, for male (n = 73) fetuses the multiples of the median (MoM; interquartile range [IQR] 1.1-1.5) was 1.3, whereas for female fetuses (n = 75) MoM was 1.1 (1.0-1.3); P < .01. Prediction of preeclampsia using ADAM12 levels was improved for pregnancies associated with a male fetus (area under receiver–operator curve [AUC] 0.73 [95% confidence interval [CI] 0.67-0.80]) than that of a female fetus (AUC 0.62 [0.55-0.70]); P = .03. The data presented here fit a contemporary hypothesis that there is a difference between the genders in response to an adverse maternal environment and suggest that an alteration in ADAM12 may reflect an altered placental response in pregnancies subsequently complicated by preeclampsia. [ABSTRACT FROM AUTHOR]

Objective: Small for gestational age (SGA) infants comprise up to 50% of all stillbirths and a minority are detected before birth. We aimed to develop and validate early pregnancy predictive models for SGA infants. Methods: 5628 participants from SCOPE, a prospective study of nulliparous pregnant women, were interviewed at 15±1 weeks’ gestation. Fetal anthropometry, uterine and umbilical Doppler studies were performed at 20±1 weeks’. The cohort was divided into training (n = 3735) and validation datasets (n = 1871). All-SGA (birthweight <10th customised centile), Normotensive-SGA (SGA with normotensive mother) and Hypertensive-SGA (SGA with mother who developed hypertension) were the primary outcomes. Multivariable analysis was performed using stepwise logistic regression firstly using clinical variables and then with clinical and ultrasound variables. Receiver operator curves were constructed and areas under the curve (AUC) calculated. Results: 633 infants (11.3%) in the whole cohort were SGA; 465 (8.3%) Normotensive-SGA and 165 (3.0%) Hypertensive-SGA. In the training dataset risk factors for All-SGA at 15±1 weeks’ included: family history of coronary heart disease, maternal birthweight <3000 g and 3000 g to 3499 g compared with ≥3500 g, >12 months to conceive, university student, cigarette smoking, proteinuria, daily vigorous exercise and diastolic blood pressure ≥80. Recreational walking ≥4 times weekly, rhesus negative blood group and increasing random glucose were protective. AUC for clinical risk factors was 0.63. Fetal abdominal or head circumference z scores <10th centile and increasing uterine artery Doppler resistance at 20±1 weeks’ were associated with increased risk. Addition of these parameters increased the AUC to 0.69. Clinical predictors of Normotensive and Hypertensive-SGA were sub-groups of All-SGA predictors and were quite different. The combined clinical and ultrasound AUC for Normotensive and Hypertensive-SGA were 0.69 and 0.82 respectively. Conclusion: Predictors for SGA of relevance to clinical practice were identified. The identity and predictive potential differed in normotensive women and those who developed hypertension. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective. To develop clinical risk tools for preeclampsia and small for gestational age (SGA) in high-risk women. Methods. 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. Results. 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. Conclusion. Multiple clinical risk factors increase the risk of preeclampsia and SGA. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine (1). whether the inherited thrombophilias (the factor V Leiden and prothrombin gene mutations and the methylenetetrahydrofolate reductase [C677T] polymorphism) are increased in women with "idiopathic" (normotensive) small-for-gestational-age pregnancies and/or in their babies and (2). whether fetal carriage of a thrombophilia is associated with abnormal umbilical Doppler studies.Study Design: This was a case-controlled study of normotensive women who were delivered of a singleton small-for-gestational-age baby (birth weight, <10th percentile adjusted for sex) with no clinical evidence of chromosomal or congenital abnormality. Control subjects were healthy women who were delivered of appropriate-for-gestational-age babies.Results: One hundred forty-five women with small-for-gestational-age pregnancies and 290 control subjects were recruited. Small-for-gestational-age babies were born at an earlier gestational age (38 +/- 3.0 weeks) and with a lower birth weight (2373 +/- 521 g) than control babies (39.7 +/- 1.3 weeks and 3606 +/- 423 g, P <.01). There were no differences in the rates of factor V Leiden (2.8% vs 3.8%; relative risk, 0.79; 95% CI, 0.34-1.85), prothrombin gene mutation (2.8% vs 3.1%; relative risk, 0.92; 95% CI, 0.40-2.09), and methylenetetrahydrofolate reductase C677T polymorphism (13% vs 9%; relative risk, 1.27; 95% CI, 0.87-1.84) between mothers with small-for-gestational-age babies and control subjects, respectively. Inherited thrombophilias were not increased in small-for-gestational-age babies compared with control babies. Of small-for-gestational-age babies with abnormal umbilical artery Doppler studies (n = 25), 21% had a thrombophilia compared with 11% with normal umbilical artery Doppler studies (n = 68; relative risk, 1.75; 95% CI, 0.81-3.81).Conclusion: The rates of these inherited thrombophilias are not increased in normotensive women with small-for-gestational-age pregnancies. Further studies are required to determine whether thrombophilias are increased in small-for-gestational-age babies with abnormal umbilical Doppler study results. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine whether, in women who are at high risk of the development of preeclampsia, serum activin A concentrations are elevated before the disease and whether activin A is a useful predictor of preeclampsia.Study Design: Sera were collected on five occasions throughout pregnancy from women with chronic hypertension, renal disease, or previous early-onset preeclampsia (n = 80 women). Women were classified as control subjects (normotensive or stable chronic hypertension), gestational hypertensive, or preeclamptic (de novo or superimposed). Serum activin A concentrations were measured by immunoassay. Differences in activin A concentrations between groups were analyzed with the use of a mixed-models procedure; screening test characteristics were calculated.Results: Twenty-six women (33%) had gestational hypertension, and 17 women (21%) had preeclampsia or superimposed preeclampsia. Serum activin A levels increased with gestation in all groups (P =.0001), but there were no significant difference in activin A levels between groups (P =.75).Conclusion: In women who were at high risk of the development of preeclampsia, serum activin A levels are not elevated with preeclampsia. Activin A is not a useful predictor of preeclampsia in this setting. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Complicated pregnancies demonstrate abnormal decidual and placental villous vasculature. We examined maternal concentrations of vascular endothelial growth factor and placental growth factor in normal pregnancies and in pregnancies that were complicated by isolated idiopathic small-for-gestationalage (SGA) newborn infants, preeclampsia alone, or preeclampsia with SGA newborn infants at the time of clinical disease and before the onset of clinical signs. STUDY DESIGN: Serum vascular endothelial growth factor and placental growth factor were measured by enzyme-linked immunosorbent assay in cross-sectional and longitudinal cohorts of pregnant nulliparous women. The results were compared by Wilcoxon tests or a mixed-models method, respectively. RESULTS: In the cross-sectional study, serum placental growth factor was reduced in abnormal pregnancy relative to control subjects (SGA newborn infants, 18 [P = .04]; preeclampsia, 20; or preeclampsia with smallfor-gestational-age newborn infants, 11 [P = .0001]) as early as 15 to 19 weeks of gestation in preeclampsia with SGA newborn infants. Vascular endothelial growth factor was <30 pg/mL in all serum specimens from pregnant women. CONCLUSION: We postulate that decreased placental growth factor production results in abnormalities of placental angiogenesis through direct and indirect effects on other vasculotropic growth factors. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to determine whether the secretory component of immunoglobulin A in maternal serum predicts delivery before 34 weeks' gestation.Study Design: Primigravid women of an urban population in New Zealand were recruited at booking into a prospective longitudinal nested case control study (n = 1651; after exclusions and withdrawals, n = 1511). Serum was collected at 8 to 12 weeks, 15 to 18 weeks, 21 to 24 weeks, 28 to 30 weeks, and 36 to 38 weeks of gestation and 6 weeks post partum. Concentrations of the secretory component of immunoglobulin A were determined by enzyme-linked immunosorbent assay in all women who were delivered preterm (n = 53) and in controls randomly selected from women delivered at > or =37 weeks' gestation (n = 178).Results: Serum concentrations of the secretory component of immunoglobulin A were similar in women delivered at term or preterm throughout pregnancy (n = 21 delivered at <34 weeks and n = 32 at 34 to 36.9 weeks, incidence 3.5%). Receiver-operator characteristic curves showed no discriminating ability of the secretory component of immunoglobulin A. Smokers had 50% higher concentrations than nonsmokers did (p < 0.0001 by analysis of variance).Conclusion: The secretory component of immunoglobulin A in maternal serum does not predict preterm delivery in a low-risk population. [ABSTRACT FROM AUTHOR]

The authors explores the link between pre-eclampsia related vascular injury within the thyroid and the development of subclinical hypothyroidism in women. They discuss a study which investigated the association between increased rate of sublinical hypothyroidism with pre-eclampsia in pregnant women. They call for further studies on the possibility of residual vascular damage after pre-eclampsia. The authors also suggest that evidence from randomised controlled trials is needed before considering thyroxine replacement.

The article discusses the findings of a study on the risks of spontaneous preterm birth and of having a small for gestational age infant in pregnant women who stopped smoking by 15 weeks of gestation. The study recruited healthy nulliparous women to the Screening for Pregnancy Endpoints (SCOPE) study in Auckland, New Zealand and Adelaide, South Australia between November 2004 and July 2007. It showed no significant differences in adverse pregnancy outcomes between women in their 15 weeks of gestation who stopped smoking and those who do not smoke. However, women who smoked during pregnancy had higher rates of preterm birth and small for gestational age infants.