Prediction of complications in early-onset pre-eclampsia (PREP): development and external multinational validation of prognostic models.

BACKGROUND: Unexpected clinical deterioration before 34 weeks gestation is an undesired course in early-onset pre-eclampsia. To safely prolong preterm gestation, accurate and timely prediction of complications is required. METHOD: Women with confirmed early onset pre-eclampsia were recruited from 53 maternity units in the UK to a large prospective cohort study (PREP-946) for development of prognostic models for the overall risk of experiencing a complication using logistic regression (PREP-L), and for predicting the time to adverse maternal outcome using a survival model (PREP-S). External validation of the models were carried out in a multinational cohort (PIERS-634) and another cohort from the Netherlands (PETRA-216). Main outcome measures were C-statistics to summarise discrimination of the models and calibration plots and calibration slopes. RESULTS: A total of 169 mothers (18%) in the PREP dataset had adverse outcomes by 48 hours, and 633 (67%) by discharge. The C-statistics of the models for predicting complications by 48 hours and by discharge were 0.84 (95% CI, 0.81-0.87; PREP-S) and 0.82 (0.80-0.84; PREP-L), respectively. The PREP-S model included maternal age, gestation, medical history, systolic blood pressure, deep tendon reflexes, urine protein creatinine ratio, platelets, serum alanine amino transaminase, urea, creatinine, oxygen saturation and treatment with antihypertensives or magnesium sulfate. The PREP-L model included the above except deep tendon reflexes, serum alanine amino transaminase and creatinine. On validation in the external PIERS dataset, the reduced PREP-S model showed reasonable calibration (slope 0.80) and discrimination (C-statistic 0.75) for predicting adverse outcome by 48 hours. Reduced PREP-L model showed excellent calibration (slope: 0.93 PIERS, 0.90 PETRA) and discrimination (0.81 PIERS, 0.75 PETRA) for predicting risk by discharge in the two external datasets. CONCLUSIONS: PREP models can be used to obtain predictions of adverse maternal outcome risk, including early preterm delivery, by 48 hours (PREP-S) and by discharge (PREP-L), in women with early onset pre-eclampsia in the context of current care. They have a potential role in triaging high-risk mothers who may need transfer to tertiary units for intensive maternal and neonatal care. TRIAL REGISTRATION: ISRCTN40384046 , retrospectively registered.

Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis.

OBJECTIVE: To determine the risks of stillbirth and neonatal complications by gestational age in uncomplicated monochorionic and dichorionic twin pregnancies. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane databases (until December 2015). REVIEW METHODS: Databases were searched without language restrictions for studies of women with uncomplicated twin pregnancies that reported rates of stillbirth and neonatal outcomes at various gestational ages. Pregnancies with unclear chorionicity, monoamnionicity, and twin to twin transfusion syndrome were excluded. Meta-analyses of observational studies and cohorts nested within randomised studies were undertaken. Prospective risk of stillbirth was computed for each study at a given week of gestation and compared with the risk of neonatal death among deliveries in the same week. Gestational age specific differences in risk were estimated for stillbirths and neonatal deaths in monochorionic and dichorionic twin pregnancies after 34 weeks' gestation. RESULTS: 32 studies (29 685 dichorionic, 5486 monochorionic pregnancies) were included. In dichorionic twin pregnancies beyond 34 weeks (15 studies, 17 830 pregnancies), the prospective weekly risk of stillbirths from expectant management and the risk of neonatal death from delivery were balanced at 37 weeks' gestation (risk difference 1.2/1000, 95% confidence interval -1.3 to 3.6; I(2)=0%). Delay in delivery by a week (to 38 weeks) led to an additional 8.8 perinatal deaths per 1000 pregnancies (95% confidence interval 3.6 to 14.0/1000; I(2)=0%) compared with the previous week. In monochorionic pregnancies beyond 34 weeks (13 studies, 2149 pregnancies), there was a trend towards an increase in stillbirths compared with neonatal deaths after 36 weeks, with an additional 2.5 per 1000 perinatal deaths, which was not significant (-12.4 to 17.4/1000; I(2)=0%). The rates of neonatal morbidity showed a consistent reduction with increasing gestational age in monochorionic and dichorionic pregnancies, and admission to the neonatal intensive care unit was the commonest neonatal complication. The actual risk of stillbirth near term might be higher than reported estimates because of the policy of planned delivery in twin pregnancies. CONCLUSIONS: To minimise perinatal deaths, in uncomplicated dichorionic twin pregnancies delivery should be considered at 37 weeks' gestation; in monochorionic pregnancies delivery should be considered at 36 weeks. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014007538.

Prognostic models in obstetrics: available, but far from applicable.

Health care provision is increasingly focused on the prediction of patients' individual risk for developing a particular health outcome in planning further tests and treatments. There has been a steady increase in the development and publication of prognostic models for various maternal and fetal outcomes in obstetrics. We undertook a systematic review to give an overview of the current status of available prognostic models in obstetrics in the context of their potential advantages and the process of developing and validating models. Important aspects to consider when assessing a prognostic model are discussed and recommendations on how to proceed on this within the obstetric domain are given. We searched MEDLINE (up to July 2012) for articles developing prognostic models in obstetrics. We identified 177 papers that reported the development of 263 prognostic models for 40 different outcomes. The most frequently predicted outcomes were preeclampsia (n = 69), preterm delivery (n = 63), mode of delivery (n = 22), gestational hypertension (n = 11), and small-for-gestational-age infants (n = 10). The performance of newer models was generally not better than that of older models predicting the same outcome. The most important measures of predictive accuracy (ie, a model's discrimination and calibration) were often (82.9%, 218/263) not both assessed. Very few developed models were validated in data other than the development data (8.7%, 23/263). Only two-thirds of the papers (62.4%, 164/263) presented the model such that validation in other populations was possible, and the clinical applicability was discussed in only 11.0% (29/263). The impact of developed models on clinical practice was unknown. We identified a large number of prognostic models in obstetrics, but there is relatively little evidence about their performance, impact, and usefulness in clinical practice so that at this point, clinical implementation cannot be recommended. New efforts should be directed toward evaluating the performance and impact of the existing models.

Epilepsy in pregnancy and reproductive outcomes: a systematic review and meta-analysis.

BACKGROUND: Antenatal care of women with epilepsy is varied. The association of epilepsy and antiepileptic drug exposure with pregnancy outcomes needs to be quantified to guide management. We did a systematic review and meta-analysis to investigate the association between epilepsy and reproductive outcomes, with or without exposure to antiepileptic drugs. METHODS: We searched MEDLINE, Embase, Cochrane, AMED, and CINAHL between Jan 1, 1990, and Jan 21, 2015, with no language or regional restrictions, for observational studies of pregnant women with epilepsy, which assessed the risk of obstetric complications in the antenatal, intrapartum, or postnatal period, and any neonatal complications. We used the Newcastle-Ottawa Scale to assess the methodological quality of the included studies, risk of bias in the selection and comparability of cohorts, and outcome. We assessed the odds of maternal and fetal complications (excluding congenital malformations) by comparing pregnant women with and without epilepsy and undertook subgroup analysis based on antiepileptic drug exposure in women with epilepsy. We summarised the association as odds ratio (OR; 95% CI) using random effects meta-analysis. The PROSPERO ID of this Systematic Review's protocol is CRD42014007547. FINDINGS: Of 7050 citations identified, 38 studies from low-income and high-income countries met our inclusion criteria (39 articles including 2,837,325 pregnancies). Women with epilepsy versus those without (2,809,984 pregnancies) had increased odds of spontaneous miscarriage (OR 1·54, 95% CI 1·02-2·32; I(2)=67%), antepartum haemorrhage (1·49, 1·01-2·20; I(2)=37%), post-partum haemorrhage (1·29, 1·13-1·49; I(2)=41%), hypertensive disorders (1·37, 1·21-1·55; I(2)=23%), induction of labour (1·67, 1·31-2·11; I(2)=64%), caesarean section (1·40, 1·23-1·58; I(2)=66%), any preterm birth (<37 weeks of gestation; 1·16, 1·01-1·34; I(2)=64%), and fetal growth restriction (1·26, 1·20-1·33; I(2)=1%). The odds of early preterm birth, gestational diabetes, fetal death or stillbirth, perinatal death, or admission to neonatal intensive care unit did not differ between women with epilepsy and those without the disorder. INTERPRETATION: A small but significant association of epilepsy, exposure to antiepileptic drugs, and adverse outcomes exists in pregnancy. This increased risk should be taken into account when counselling women with epilepsy. FUNDING: EBM CONNECT Collaboration.