David Arroyo-Manzano

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 Reviews 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.

Anaesthesia-related maternal mortality in low-income and middle-income countries: a systematic review and meta-analysis

BACKGROUND The risk factors contributing to maternal mortality from anaesthesia in low-income and middle-income countries and the burden of the problem have not been comprehensively studied up to now. We aimed to obtain precise estimates of anaesthesia-attributed deaths in pregnant women exposed to anaesthesia and to identify the factors linked to adverse outcomes in pregnant women exposed to anaesthesia in low-income and middle-income countries. METHODS In this systematic review and meta-analysis, we searched major electronic databases from inception until Oct 1, 2015, for studies reporting risks of maternal death from anaesthesia in low-income and middle-income countries. Studies were included if they assessed maternal and perinatal outcomes in pregnant women exposed to anaesthesia for an obstetric procedure in countries categorised as low-income or middle-income by the World Bank. We excluded studies in high-income countries, those involving non-pregnant women, case reports, and studies published before 1990 to ensure that the estimates reflect the current burden of the condition. Two independent reviewers undertook quality assessment and data extraction. We computed odds ratios for risk factors and anaesthesia-related complications, and pooled them using a random effects model. This study is registered with PROSPERO, number CRD42015015805. FINDINGS 44 studies (632,556 pregnancies) reported risks of death from anaesthesia in women who had an obstetric surgical procedure; 95 (32,149,636 pregnancies and 36,144 deaths) provided rates of anaesthesia-attributed deaths as a proportion of maternal deaths. The risk of death from anaesthesia in women undergoing obstetric procedures was 1·2 per 1000 women undergoing obstetric procedures (95% CI 0·8-1·7, I(2)=83%). Anaesthesia accounted for 2·8% (2·4-3·4, I(2)=75%) of all maternal deaths, 3·5% (2·9-4·3, I(2)=79%) of direct maternal deaths (ie, those that resulted from obstetric complications), and 13·8% (9·0-20·7, I(2)=84%) of deaths after caesarean section. Exposure to general anaesthesia increased the odds of maternal (odds ratio [OR] 3·3, 95% CI 1·2-9·0, I(2)=58%), and perinatal deaths (2·3, 1·2-4·1, I(2)=73%) compared with neuraxial anaesthesia. The rate of any maternal death was 9·8 per 1000 anaesthetics (5·2-15·7, I(2)=92%) when managed by non-physician anaesthetists compared with 5·2 per 1000 (0·9-12·6, I(2)=95%) when managed by physician anaesthetists. INTERPRETATION The current international priority on strengthening health systems should address the risk factors such as general anaesthesia and rural setting for improving anaesthetic care in pregnant women. FUNDING Ammalife Charity and ELLY Appeal, Barts Charity.

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; I2=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; I2=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; I2=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.

Cognitive, motor, behavioural and academic performances of children born preterm: a meta-analysis and systematic review involving 64 061 children

Preterm birth may leave the brain vulnerable to dysfunction. Knowledge of future neurodevelopmental delay in children born with various degrees of prematurity is needed to inform practice and policy.

Type of obstetric anesthesia administered and complications in women with preeclampsia in low- and middle-income countries: A systematic review.

ABSTRACT Background: Delivery is often expedited with cesarean section, necessitating anesthesia, to prevent complications in women with preeclampsia. Anesthesia-associated risks in these women from low- and middle-income countries (LMICs) are not known. Methods: We searched major databases (until February 2017) for studies on general vs. regional anesthesia in women with preeclampsia. We summarized the association between outcomes and type of anesthesia using a random effects model and reported as odds ratio (OR) with 95% confidence intervals (95% CIs). Findings: We included 14 studies (10,411 pregnancies). General anesthesia was associated with an increase in the odds of maternal death sevenfold (OR 7.70, 95% CI 1.9 to 31.0, I2 = 58%) than regional anesthesia. The odds of pulmonary edema (OR 5.16, 95% CI 2.5 to 10.4, I2 = 0%), maternal intensive care unit admissions (OR 16.25, 95% CI 9.0 to 29.5, I2 = 65%), and perinatal death (OR 3.01, 95% CI 1.4 to 6.5, I2 = 56%) were increased with general vs. regional anesthesia. Conclusion: General anesthesia is associated with increased complications in women with preeclampsia undergoing cesarean section in LMIC.