Buprenorphine Compared with Methadone in Pregnancy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Illicit opioid use in pregnancy is associated with adverse maternal, neonatal, and childhood outcomes. Opioid substitution is recommended, but whether methadone or buprenorphine is the optimal agent remains unclear. METHODS: We searched EMBASE, PubMed, Web of Science, Scopus, Open Gray, CINAHL and the Cochrane Central Registry of Controlled Trials (CENTRAL) from inception to April 2020 for randomized controlled trials (RCTs) and cohort studies comparing methadone and buprenorphine treatment for opioid-using mothers. Included studies assessed maternal and or neonatal outcomes. We used random-effects meta-analyses to estimate summary measures for outcomes and report these separately for RCTs and cohort studies. RESULTS: Of 408 abstracts screened, 20 papers were included (4 RCTs, 16 cohort, 223 and 7028 participants respectively). All RCTs (4/4) had a high risk of bias and median (IQR) Newcastle Ottawa Scale for cohort studies was 7.5 (6-9). In both RCTs and cohort studies, buprenorphine was associated with; greater offspring birth weight (weighted mean difference [WMD] 343 g (95% CI: 40-645 g) in RCT and 184 g (95% CI: 121-247 g) in cohort studies); body length at birth (WMD 2.28 cm (95% CI: 1.06-3.49 cm) in RCTs and 0.65 cm (95% CI: 0.31-0.98 cm) in cohort studies); and reduced risk of prematurity (risk ratio [RR] 0.41 (95% CI: 0.18-0.93) in RCTs and 0.63 [95% CI: 0.53-0.75] in cohort studies) when compared to methadone. All other clinical outcomes were comparable. CONCLUSIONS: Compared to methadone, buprenorphine was consistently associated with improved birthweight and gestational age, however given potential biases, results should be interpreted with caution.

Epidural analgesia during labour and severe maternal morbidity: population based study.

OBJECTIVES: To determine the effect of labour epidural on severe maternal morbidity (SMM) and to explore whether this effect might be greater in women with a medical indication for epidural analgesia during labour, or with preterm labour. DESIGN: Population based study. SETTING: All NHS hospitals in Scotland. PARTICIPANTS: 567 216 women in labour at 24+0 to 42+6 weeks' gestation between 1 January 2007 and 31 December 2019, delivering vaginally or through unplanned caesarean section. MAIN OUTCOME MEASURES: The primary outcome was SMM, defined as the presence of ≥1 of 21 conditions used by the US Centers for Disease Control and Prevention (CDC) as criteria for SMM, or a critical care admission, with either occurring at any point from date of delivery to 42 days post partum (described as SMM). Secondary outcomes included a composite of ≥1 of the 21 CDC conditions and critical care admission (SMM plus critical care admission), and respiratory morbidity. RESULTS: Of the 567 216 women, 125 024 (22.0%) had epidural analgesia during labour. SMM occurred in 2412 women (4.3 per 1000 births, 95% confidence interval (CI) 4.1 to 4.4). Epidural analgesia was associated with a reduction in SMM (adjusted relative risk 0.65, 95% CI 0.50 to 0.85), SMM plus critical care admission (0.46, 0.29 to 0.73), and respiratory morbidity (0.42, 0.16 to 1.15), although the last of these was underpowered and had wide confidence intervals. Greater risk reductions in SMM were detected among women with a medical indication for epidural analgesia (0.50, 0.34 to 0.72) compared with those with no such indication (0.67, 0.43 to 1.03; P<0.001 for difference). More marked reductions in SMM were seen in women delivering preterm (0.53, 0.37 to 0.76) compared with those delivering at term or post term (1.09, 0.98 to 1.21; P<0.001 for difference). The observed reduced risk of SMM with epidural analgesia was increasingly noticeable as gestational age at birth decreased in the whole cohort, and in women with a medical indication for epidural analgesia. CONCLUSION: Epidural analgesia during labour was associated with a 35% reduction in SMM, and showed a more pronounced effect in women with medical indications for epidural analgesia and with preterm births. Expanding access to epidural analgesia for all women during labour, and particularly for those at greatest risk, could improve maternal health.