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

Abstract

Objectives To develop a predictive model for preeclampsia 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 preeclampsia, including 47 (1.3%) with preterm preeclampsia. 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 preeclampsia. 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.

The relationship between 25-hydroxyvitamin D concentration in early pregnancy and pregnancy outcomes in a large, prospective cohort

“…Pre-eclampsia was diagnosed according to the International Society for the Study of Hypertension in Pregnancy criteria (14) as gestational hypertension (systolic blood pressure of ≥140 mmHg and/or diastolic blood pressure of ≥90 mmHg on at least two occasions) with proteinuria or any multisystem complication of pre-eclampsia (15) . SGA was defined as weight below the 10th customised birth weight centile (16) , and spontaneous preterm birth was defined as delivery before 37 weeks of gestation.…”

“…Participants were also asked to rate their physical activity (over the previous 3 months) as vigorous, moderate, recreational walking or no physical activity, and the frequency at which they engaged in physical activity was recorded. Data were entered into an Internet-accessed, password-protected, centralised database with complete audit train (MedSciNet AB ).Pre-eclampsia was diagnosed according to the International Society for the Study of Hypertension in Pregnancy criteria (14) as gestational hypertension (systolic blood pressure of ≥140 mmHg and/or diastolic blood pressure of ≥90 mmHg on at least two occasions) with proteinuria or any multisystem complication of pre-eclampsia (15) . SGA was defined as weight below the 10th customised birth weight centile (16) , and spontaneous preterm birth was defined as delivery before 37 weeks of gestation.…”

Low molecular weight heparin for the prevention of severe preeclampsia: where next?

“…The potential maternal and perinatal complications of preeclampsia are significant, including maternal seizures, fetal growth restriction (FGR) and stillbirth. Approximately 5% of women develop preeclampsia, with the majority of women experiencing mild preeclampsia that occurs near term and is safely managed by delivery [2]. Only 1% of pregnant women develop early-onset preeclampsia, where both the maternal and fetal implications are substantially greater, typically resulting in FGR and the need for iatrogenic preterm delivery before 34 weeks' gestation [2].…”

“…A patient population that is at high risk of severe preeclampsia is low, approximately 1% [2]. Importantly, LMWH is a costly therapy.…”

“…Approximately 5% of women develop preeclampsia, with the majority of women experiencing mild preeclampsia that occurs near term and is safely managed by delivery [2]. Only 1% of pregnant women develop early-onset preeclampsia, where both the maternal and fetal implications are substantially greater, typically resulting in FGR and the need for iatrogenic preterm delivery before 34 weeks' gestation [2]. Early-onset preeclampsia is hypothesized to be a direct consequence of the interactions between a dysfunctional placenta and maternal cardiovascular system, while late-onset preeclampsia is hypothesized to be largely triggered by maternal constitutional factors [3][4][5].…”