Schizophrenia pregnancies should be given greater health priority in the global health agenda: results from a large-scale meta-analysis of 43,611 deliveries of women with schizophrenia and 40,948,272 controls

Abstract

Women with schizophrenia and their newborns are at risk of adverse pregnancy, delivery, neonatal and child outcomes. However, robust and informative epidemiological estimates are lacking to guide health policies to prioritise and organise perinatal services. For the first time, we carried out a systematic review and meta-analysis to synthesise the accumulating evidence on pregnancy, delivery, neonatal complications, and infant mortality among women with schizophrenia and their newborns (N = 43,611) vs. controls (N = 40,948,272) between 1999 and 2021 (26 population-based studies from 11 high-income countries) using random effects. Women with schizophrenia had higher odds (OR) of gestational diabetes (2.35, 95% CI: [1.57-3.52]), gestational hypertension, pre-eclampsia/eclampsia (OR 1.55, 95% CI: [1.02-2.36]; 1.85, 95% CI: [1.52-2.25]), antepartum and postpartum haemorrhage (OR 2.28, 95% CI: [1.58-3.29]; 1.14, 95% CI: [1.04-1.24]), placenta abruption, threatened preterm labour, and premature rupture of membrane (OR 2.20, 95% CI: [2.02-2.39]; 2.91, 95% CI: [1.57-5.40]; 1.29, 95% CI: [1.06-1.58]), c-section (OR 1.33, 95% CI: [1.22-1.45]), foetal distress (OR 1.80, 95% CI: [1.43-2.26]), preterm and very preterm delivery (OR 1.79, 95% CI: [1.62-1.98]; 2.31, 95% CI: [1.78-2.98]), small for gestational age and low birth weight (OR 1.63, 95% CI: [1.48-1.80]; 1.75, 95% CI: [1.46-2.11]), congenital malformations (OR 1.86, 95% CI: [1.71-2.03]), and stillbirths (OR 2.06, 95% CI: [1.83-2.31]). Their newborns had higher odds of neonatal death (OR 1.41, 95% CI: [1.03-1.94]), post-neonatal death (OR 2.87, 95% CI: [2.11-3.89]) and infant mortality (OR 2.33, 95% CI: [1.81-3.01]). This large-scale meta-analysis confirms that schizophrenia is associated with a substantially increased risk of very preterm delivery, stillbirth, and infant mortality, and metabolic risk in mothers. No population-based study has been carried out in low- and middle-income countries in which health problems of women with schizophrenia are probably more pronounced. More research is needed to better understand the complex needs of women with schizophrenia and their newborns, determine how care delivery could be optimised, and define best practices. Study registration: PROSPERO CRD42020197446.