Cardiometabolic Complications in Pregnancy and Biological Ageing in the Offspring: A Systematic Review and Meta‐Analysis

Background Cardiometabolic complications in pregnancy may alter the intrauterine environment, influence offspring biological ageing and potentially increase the risk of chronic diseases later in life. Objectives This systematic review and meta‐analysis aimed to examine associations between diabetes in pregnancy, hypertensive disorders of pregnancy, maternal BMI and metabolic syndrome, and offspring biological ageing markers, including telomere length and DNA methylation. Data Sources Studies were retrieved from PubMed, EMBASE, Scopus and Web of Science. Study Selection and Data Extraction Study characteristics, exposures and outcomes were independently extracted and summarised. Synthesis Standardised mean differences in telomere length were calculated using Hedges' g, and random effects meta‐analysis was applied to pool effect estimates. Results Of the 123 studies, 90 assessed DNA methylation, 28 reported telomere length and 5 reported both outcomes. No differences in telomere length were observed in offspring exposed to gestational diabetes (7 studies) or hypertensive disorders (14 studies). Each unit increase in maternal BMI was associated with a 0.27% decrease in offspring telomere length (3 studies). Exposure to cardiometabolic complications was associated with aberrant DNA methylation patterns in genes related to cardiometabolic pathways. Higher mean methylation level was reported in cord blood (2 studies) and placenta (7 studies) following exposure to diabetes and hypertensive disorders. Conclusions Higher maternal BMI was associated with slightly shorter offspring telomeres, while no differences were observed following exposure to gestational diabetes or hypertensive disorders. Altered DNA methylation in cardiometabolic genes suggests epigenetic effects of in utero exposure, although heterogeneity in biospecimens and measurement methods limits definitive conclusions.