Early-life risk factors and cardiometabolic outcomes in children and adolescents: a systematic review and meta-analysis

Abstract

Early-life metabolic, endocrine, and nutritional exposures may be associated with later cardiometabolic health. We aimed to identify early-life risk factors occurring during preconception, pregnancy and birth, and infancy up to 2 years that are associated with glucose intolerance, dyslipidemia, hypertension, metabolic syndrome, and type 2 diabetes (T2D) in children and adolescents. This systematic review (PROSPERO CRD42022355152) included prospective and retrospective longitudinal observational studies, case-control studies, and randomized controlled trials (RCTs) identified in selected electronic databases through February 20, 2025. Of 18,765 screened records, 70 met the inclusion criteria (65 longitudinal observational studies, four case-control studies, and one RCT). Risk-factor quality was assessed according to modifiability and predictive power. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects models. Meta-analyses based on fewer than five independent studies were classified as exploratory. Gestational diabetes mellitus (GDM) was positively associated with every cardiometabolic risk outcome, with glucose intolerance being the most frequently reported. The odds of developing glucose intolerance were significantly higher in children and adolescents exposed to GDM (OR: 2.13, 95% CI: 1.58–2.86; I² = 12.7%), based on a revised meta-analysis retaining only one independent estimate per source cohort. In addition, exploratory analyses suggested higher odds of hypertension in children born small for gestational age (SGA); the corresponding exploratory analysis for preterm birth and elevated systolic blood pressure did not reach statistical significance and is presented for methodological illustration only. Maternal pregnancy body mass index (BMI) was positively associated with glucose intolerance, dyslipidemia, hypertension, and metabolic syndrome, whereas infant BMI and weight changes were positively associated with dyslipidemia, hypertension, and metabolic syndrome. Limited evidence suggested a possible inverse association between breastfeeding and cardiometabolic risk in childhood and adolescence, based on few studies per outcome. GDM, low or high birth weight, SGA or large for gestational age, maternal pregnancy BMI, and infant BMI or weight changes were associated with cardiometabolic outcomes in childhood and adolescence. Evidence for an inverse association with breastfeeding was limited and inconclusive. These findings may support closer cardiometabolic monitoring of children with relevant early-life exposures and inform future prevention research.