Neurodevelopmental Pathways from Maternal Obesity to Offspring Outcomes: An Umbrella Review of Cognitive and Behavioral Consequences Across Development.

Background: Maternal obesity affects 20-25% of pregnancies globally and has been associated with adverse offspring neurodevelopmental outcomes. This umbrella review synthesized evidence on neurodevelopmental pathways linking maternal obesity to offspring cognitive, executive, and behavioral outcomes. Methods: Following PRISMA 2020 guidelines, we systematically searched six databases (PubMed/MEDLINE, Scopus, Web of Science, PsycINFO, EMBASE, CINAHL) for studies published 2008-2024. We included original peer-reviewed studies examining maternal pre-pregnancy obesity (BMI ≥ 30 kg/m2) and offspring neurodevelopmental outcomes using prospective cohort, experimental, neuroimaging, or systematic review designs with validated assessments. Risk of bias was assessed using Newcastle-Ottawa Scale, Cochrane RoB 2.0, and SYRCLE guidelines. Results: Analysis of 78 studies encompassing 650,000+ mother-child pairs from 17 countries revealed significant associations. Study designs included prospective cohorts (59%), animal experiments (22%), systematic reviews/meta-analyses (13%), neuroimaging studies (4%), and randomized trials (3%). Maternal obesity (BMI ≥ 30 kg/m2) was associated with reduced cognitive abilities (IQ differences: -2.5 to -5.8 points), impaired executive function (OR 1.4-2.3), and increased ADHD symptoms (OR 1.4-2.8) and emotional dysregulation (OR 1.5-2.2). Dose-response relationships revealed threshold effects at BMI ≥ 30 kg/m2, accelerating at BMI ≥ 35 kg/m2. Four primary mechanistic pathways were identified: inflammatory, metabolic, epigenetic, and neurotransmitter alterations. Only 57.7% of studies used prospectively measured pre-pregnancy BMI. Conclusions: Observational and experimental evidence indicates maternal obesity represents a modifiable risk factor for offspring neurodevelopmental impairment. The primarily observational human evidence, supported by mechanistic animal studies, suggests multimodal interventions targeting identified pathways during critical windows (pre-conception through early postnatal period) warrant investigation.