While there is clear evidence that severe maternal morbidity (SMM) contributes significantly to poor maternal health outcomes, limited data exist on its impact on perinatal outcomes. We undertook a systematic review and meta-analysis to ascertain the association between SMM and adverse perinatal outcomes in high-income countries (HICs). We searched for full-text publications in PubMed, Embase, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Scopus databases. Studies that reported data on the association of SMM and adverse perinatal outcomes, either as a composite or individual outcome, were included. Two authors independently assessed study eligibility, extracted data, and performed quality assessment using the Newcastle–Ottawa Scale. We used random-effects modelling to calculate odds ratios (ORs) with 95% confidence intervals. We also assessed the risk of publication bias and statistical heterogeneity using funnel plots and Higgins I2, respectively. We defined sub-groups of SMM as hemorrhagic disorders, hypertensive disorders, cardiovascular disorders, hepatic disorders, renal disorders, and thromboembolic disorders. Adverse perinatal outcome was defined as preterm birth (before 37 weeks gestation), small for gestational age (SGA) (birth weight (BW) < 10th centile for gestation), low birthweight (LBW) (BW < 2.5 kg), Apgar score < 7 at 5 min, neonatal intensive care unit (NICU) admission, stillbirth and perinatal death (stillbirth and neonatal deaths up to 28 days). A total of 35 studies consisting of 38,909,426 women were included in the final analysis. SMMs associated with obstetric hemorrhage (OR 3.42, 95% CI: 2.55–4.58), severe hypertensive disorders (OR 6.79, 95% CI: 6.06–7.60), hepatic (OR 3.19, 95% CI: 2.46–4.13) and thromboembolic disorders (OR 2.40, 95% CI: 1.67–3.46) were significantly associated with preterm birth. SMMs from hypertensive disorders (OR 2.86, 95% CI: 2.51–3.25) or thromboembolic disorders (OR 1.48, 95% CI: 1.09–1.99) were associated with greater odds of having SGA infant. Women with severe hemorrhage had increased odds of LBW infant (OR 2.31, 95% CI: 1.57–3.40). SMMs from obstetric hemorrhage (OR 4.16, 95% CI: 2.54–6.81) or hypertensive disorders (OR 4.61, 95% CI: 1.17–18.20) were associated with an increased odds of low 5-min Apgar score and NICU admission (Severe obstetric hemorrhage: OR 3.34, 95% CI: 2.26–4.94 and hypertensive disorders: OR 3.63, 95% CI: 2.63–5.02, respectively). Overall, women with SMM were 4 times more likely to experience stillbirth (OR 3.98, 95% CI: 3.12–7.60) compared to those without SMM with cardiovascular disease (OR 15.2, 95% CI: 1.29–180.60) and thromboembolic disorders (OR 9.43, 95% CI: 4.38–20.29) conferring greatest risk of this complication. The odds of neonatal death were significantly higher in women with SMM (OR 3.98, 95% CI: 2.44–6.47), with those experiencing hemorrhagic (OR 7.33, 95% CI: 3.06–17.53) and hypertensive complications (OR 3.0, 95% CI: 1.78–5.07) at highest risk. Overall, SMM was also associated with higher odds of perinatal death (OR 4.74, 95% CI: 2.47–9.12) mainly driven by the increased risk in women experiencing severe obstetric hemorrhage (OR 6.18, 95% CI: 2.55–14.96). Our results highlight the importance of mitigating the impact of SMM not only to improve maternal health but also to ameliorate its consequences on perinatal outcomes.
A Systematic Review of the Safety of Blocking the IL-1 System in Human Pregnancy
