Maternal metabolic syndrome in pregnancy and child development at age 5: exploring mediating mechanisms using cord blood markers

Background: There is limited evidence on how the classification of maternal metabolic syndrome during pregnancy affects children's developmental outcomes and the possible mediators of this association. This study uses a cohort sample of 12,644 to 13,832 mother-child pairs from the UK Born in Bradford Study to examine the associations between maternal metabolic syndrome classification (MetS) and child development outcomes at age 5, using cord blood markers as candidate mediators.

Methods: Maternal cardiometabolic markers included diabetes, obesity, triglycerides, high-density lipoprotein cholesterol, blood pressure, hypertension, and fasting glucose during pregnancy. Cord blood markers of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin were used as child mediators. Child outcomes included two starting school variables: British Picture Vocabulary Scale (BPVS) and the Letter Identification Assessment (LID), and five developmental milestone domains from a national UK framework: (1) communication and language (COM); (2) personal, social, and emotional (PSE); (3) physical development (PHY); (4) literacy (LIT); and (5) mathematics (MAT). Mediation models were used to examine the associations between the classification of maternal metabolic syndrome and child developmental milestones. Models were adjusted for potential maternal, socioeconomic, and child confounders such as maternal education, deprivation, and gestational age.

Results: In mediation models, significant total effects were found for MetS associations with children's development in the LIT domain at age 5. MetS predicted individual cord blood mediators of lower HDL and increased leptin levels in both adjusted and unadjusted models. Total indirect effects (effects of all mediators combined) for MetS on a child's COM and PSE domain were significant, through all child cord blood mediators of LDL, HDL, triglycerides, adiponectin, and leptin for adjusted models.

Conclusions: The results support the hypothesis that maternal metabolic syndrome classification during pregnancy is associated with some child developmental outcomes at age 5. After adjusting for maternal, child, and environmental covariates, maternal metabolic syndrome classification during pregnancy was associated with children's LIT domain through direct effects of maternal metabolic health and indirect effects of cord blood markers (total effects), and COM and PSE domains via changes only in a child's cord blood markers (total indirect effects).