Influence of preterm birth on the association between gestational diabetes mellitus and childhood developmental vulnerability: a causal mediation analysis

Abstract Background Epidemiological studies examining the direct and indirect effects of gestational diabetes mellitus (GDM) on offspring early childhood developmental vulnerability are lacking. Therefore, the aims of this study were to estimate the direct and indirect effects of GDM (through preterm birth) on early childhood developmental vulnerability. Methods We conducted a retrospective population-based cohort study on the association between gestational diabetes mellitus and early childhood developmental vulnerability in children born in Western Australia (WA) using maternal, infant and birth records from the Midwives Notification, Hospitalizations, Developmental Anomalies, and the Australian Early Development Census (AEDC) databases. We used two aggregated outcome measures: developmentally vulnerable on at least one AEDC domain (DV1) and developmentally vulnerable on at least two AEDC domains (DV2). Causal mediation analysis was applied to estimate the natural direct (NDE), indirect (NIE), and total (TE) effects as relative risks (RR). Results In the whole cohort ( n = 64,356), approximately 22% were classified as DV1 and 11% as DV2 on AEDC domains. Estimates of the natural direct effect suggested that children exposed to GDM were more likely to be classified as DV1 (RR = 1.20, 95% CI: 1.10–1.31) and DV2 (RR = 1.34, 95% CI: 1.19–1.50) after adjusting for potential confounders. About 6% and 4% of the effect of GDM on early childhood developmental vulnerability was mediated by preterm birth for DV1 and DV2, respectively. Conclusion Children exposed to gestational diabetes mellitus were more likely to be developmentally vulnerable in one or more AEDC domains. The biological mechanism for these associations is not well explained by mediation through preterm birth.