Risk of schizophrenia in the offspring of mothers with diabetes during pregnancy: systematic review and meta-analysis.

OBJECTIVES: Hyperglycemia during pregnancy is related to adverse obstetric, neonatal, and long-term health outcomes for both mothers and the offspring. This study aimed to conduct a systematic review and meta-analysis of the global literature evaluating the association between maternal diabetes (DM) during pregnancy and the incidence of schizophrenia in the offspring. METHODS: Following PRISMA guidelines and registered in PROSPERO (CRD42024545505), a comprehensive search was conducted across major databases up to November 2024. Three retrospective cohort studies, including 2,603,889 individuals, met the inclusion criteria. RESULTS: Three studies were included in the quantitative synthesis. Meta-analysis of hazard ratios showed that maternal DM during pregnancy was associated with an increased risk of schizophrenia in the offspring (HR = 1.58; 95% CI: 1.22-2.03; P = 0.0004), with no heterogeneity (I² = 0%). Analysis based on odds ratios showed a similar trend but did not reach statistical significance (OR = 2.15; 95% CI: 0.13-34.69; P = 0.59). CONCLUSION: Maternal DM during pregnancy may be associated with an increased risk of schizophrenia in the offspring. Although maternal hyperglycemia may influence fetal neurodevelopment through inflammatory and metabolic mechanisms, the observational nature and limited number of included studies preclude causal inference, and these findings should be interpreted with caution.