Rennae S. Taylor

Clinical risk prediction for pre-eclampsia in nulliparous women: development of model in international prospective cohort

Objectives 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. Design Prospective multicentre cohort. Setting Five centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland. Participants 3572 “healthy” nulliparous women with a singleton pregnancy from a large international study; data on pregnancy outcome were available for 3529 (99%). Main outcome measure 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. Results 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. Conclusions 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.

Early pregnancy prediction of preeclampsia in nulliparous women, combining clinical risk and biomarkers: the Screening for Pregnancy Endpoints (SCOPE) international cohort study

More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks’ gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks’ gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70–0.77) and 0.68 (0.63–0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78–1.0] and 0.78 [0.58–0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia. # Novelty and Significance {#article-title-41}More than half of all cases of preeclampsia occur in healthy first-time pregnant women. Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints (SCOPE) study of low-risk nulliparous women. Forty-seven biomarkers identified on the basis of (1) association with preeclampsia, (2) a biological role in placentation, or (3) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sampled at 14 to 16 weeks’ gestation from 5623 women. The cohort was randomly divided into training (n=3747) and validation (n=1876) cohorts. Preeclampsia developed in 278 (4.9%) women, of whom 28 (0.5%) developed early-onset preeclampsia. The final model for the prediction of preeclampsia included placental growth factor, mean arterial pressure, and body mass index at 14 to 16 weeks’ gestation, the consumption of ≥3 pieces of fruit per day, and mean uterine artery resistance index. The area under the receiver operator curve (95% confidence interval) for this model in training and validation cohorts was 0.73 (0.70–0.77) and 0.68 (0.63–0.74), respectively. A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio, mean arterial pressure, any pregnancy loss <10 weeks, and mean uterine artery resistance index (area under the receiver operator curve [95% confidence interval] in training and validation cohorts, 0.89 [0.78–1.0] and 0.78 [0.58–0.99], respectively). Neither model included pregnancy-associated plasma protein A, previously reported to predict preeclampsia in populations of mixed parity and risk. In nulliparous women, combining multiple biomarkers and clinical data provided modest prediction of preeclampsia.

Evaluation of a definition of pre‐eclampsia

Objectives To determine: 1. whether an alternative definition of gestational hypertension and pre‐eclampsia stratifies women according to their risk of maternal and fetal complications; 2. whether pregnancy outcome in women with gestational hypertension differs in the presence or absence of ‘+’ proteinuria; and 3. whether a blood pressure rise of ≥ 30/15 mmHg during pregnancy is associated with adverse outcome in women who remain normotensive.

Risk factors for small-for-gestational-age infants by customised birthweight centiles: data from an international prospective cohort study

Please cite this paper as: McCowan L, Roberts C, Dekker G, Taylor R, Chan E, Kenny L, Baker P, Moss‐Morris R, Chappell L, North R on behalf of the SCOPE consortium. Risk factors for small‐for‐gestational‐age infants by customised birthweight centiles: data from an international prospective cohort study. BJOG 2010;117:1599–1607.

Duration of sexual relationship and its effect on preeclampsia and small for gestational age perinatal outcome

The aim of this study was to determine if women with preeclampsia or delivering small for gestational age (SGA) babies are more likely to have a short duration of sexual relationship compared with those who have uncomplicated pregnancies. In a prospective cohort study, 2507 nulliparous women with singleton pregnancies were interviewed at 15+/-1 weeks gestation about the duration of their sexual relationship with the biological father. Short duration of sexual relationship (< or =6 months, < or =3 months, or first intercourse) was compared between women with preeclampsia (N=131) or SGA babies (N=263) and those with uncomplicated pregnancies (N=1462). Short duration of sexual relationship was more common in women with preeclampsia compared with uncomplicated pregnancies (< or =6 months 14.5% versus 6.9%, adjusted odds ratio [adjOR] 1.88, 95% CI 1.05-3.36; < or =3 months 6.9% versus 2.5%, adjOR 2.32, 95% CI 1.03-5.25; first intercourse 1.5% versus 0.5%, adjOR 5.75, 95% CI 1.13-29.3). Although the total number of semen exposures was lower in SGA, SGA was not associated with a shorter duration of sexual relationship. On post hoc analysis, the subgroup of SGA with abnormal uterine artery Doppler at 20 weeks (N=58) were more likely to have had a short sexual relationship compared with controls (< or =6 months adjOR 2.33, 95% CI 1.09-4.98; < or =3 months adjOR 3.22, 95% CI 1.18-8.79; first intercourse adjOR 8.02, 95% CI 1.58-40.7). We conclude that compared to uncomplicated pregnancies, short duration of sexual relationship is more common in women who develop preeclampsia and women with abnormal uterine artery Doppler waveforms who deliver an SGA baby.

Risk factors for infants small for gestational age by customised birthweight centiles: data from an international prospective cohort study

Please cite this paper as: McCowan L, Roberts C, Dekker G, Taylor R, Chan E, Kenny L, Baker P, Moss‐Morris R, Chappell L, North R on behalf of the SCOPE consortium. Risk factors for small‐for‐gestational‐age infants by customised birthweight centiles: data from an international prospective cohort study. BJOG 2010;117:1599–1607.

Risk Factors for Excessive Gestational Weight Gain in a Healthy, Nulliparous Cohort

Objective. Excessive gestational weight gain (GWG) is associated with adverse maternal and child outcomes and contributes to obesity in women. Our aim was to identify early pregnancy factors associated with excessive GWG, in a contemporary nulliparous cohort. Methods. Participants in the SCOPE study were classified into GWG categories (“not excessive” versus “excessive”) based on pregravid body mass index (BMI) using 2009 Institute of Medicine (IOM) guidelines. Maternal characteristics and pregnancy risk factors at 14–16 weeks were compared between categories and multivariable analysis controlled for confounding factors. Results. Of 1950 women, 17% gained weight within the recommended range, 74% had excessive and 9% inadequate GWG. Women with excessive GWG were more likely to be overweight (adjOR 2.9 (95% CI 2.2–3.8)) or obese (adjOR 2.5 (95% CI 1.8–3.5)) before pregnancy compared to women with a normal BMI. Other factors independently associated with excessive GWG included recruitment in Ireland, younger maternal age, increasing maternal birthweight, cessation of smoking by 14–16 weeks, increased nightly sleep duration, high seafood diet, recent immigrant, limiting behaviour, and decreasing exercise by 14–16 weeks. Fertility treatment was protective. Conclusions. Identification of potentially modifiable risk factors for excessive GWG provides opportunities for intervention studies to improve pregnancy outcome and prevent maternal obesity.

Prevalence and predictors of alcohol use during pregnancy: findings from international multicentre cohort studies

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.

Gestational weight gain and adverse pregnancy outcomes in a nulliparous cohort

OBJECTIVE Excessive gestational weight gain (GWG) is an important contributing factor to the obesity epidemic in women and is associated with pregnancy complications. We investigated the relationship between GWG and caesarean delivery in labour, large for gestational age (LGA), small for gestational age (SGA) infants and pregnancy-induced hypertension by maternal pre-pregnancy body mass index (BMI) in a contemporary nulliparous cohort. STUDY DESIGN Using 2009 Institute of Medicine guidelines, participants in the SCOPE study (from Cork, Ireland, Auckland, New Zealand and Adelaide, Australia) were classified into GWG categories (low, normal and high) according to pre-pregnancy BMI. Maternal characteristics and pregnancy outcomes were compared between weight gain categories. SGA and LGA were defined as <10th and >90th customised birthweight centile. Multivariable analysis adjusted for confounding factors that impact on GWG including BMI. RESULTS Of 1950 participants, 17.2% (n=335) achieved the recommended GWG, 8.6% (n=167) had low and 74.3% (n=1448) had high GWG. Women with high GWG had increased rates of LGA infants [adjusted OR 4.45 (95% CI 2.49-7.99)] and caesarean delivery in labour [aOR 1.46 (1.03-2.07)]. SGA was increased in women with low GWG [aOR 1.79 (1.06-3.00)]. CONCLUSION Three quarters of participants had high GWG, which was associated with an independent risk of LGA infants and caesarean in labour. Low GWG was associated with SGA infants. These adverse outcomes are potentially modifiable by achievement of normal GWG, which should be an important focus of antenatal care.

Risk of First-Stage and Second-Stage Cesarean Delivery by Maternal Body Mass Index Among Nulliparous Women in Labor at Term

OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, www.anzctr.org.au, ACTRN12607000551493. LEVEL OF EVIDENCE: II