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Systematic Review

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

by
Evgenia Gkintoni
1,2,*,
Eleni Papachatzi
1,3,
Erifili Efthymiadou
4,
Emmanuella Magriplis
1,5 and
Apostolos Vantarakis
1
1
Lab. of Public Health, Department of Medicine, University of Patras, 26504 Patras, Greece
2
Department of Psychiatry, University General Hospital of Patras, 26504 Patras, Greece
3
Department of Pediatrics, University General Hospital of Patras, 26504 Patras, Greece
4
Lucy Faithfull Foundation, Epsom KT17 1HQ, UK
5
Lab. of Dietetics and Quality of Life, Department of Food Science and Human Nutrition, Agricultural University of Athens, 26504 Athens, Greece
*
Author to whom correspondence should be addressed.
Healthcare 2025, 13(20), 2653; https://doi.org/10.3390/healthcare13202653
Submission received: 21 August 2025 / Revised: 15 October 2025 / Accepted: 16 October 2025 / Published: 21 October 2025

Abstract

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.
Keywords: maternal obesity; neurodevelopment; cognitive development; executive function; ADHD; epigenetics; inflammatory pathways; developmental programming; umbrella review; behavioral outcomes maternal obesity; neurodevelopment; cognitive development; executive function; ADHD; epigenetics; inflammatory pathways; developmental programming; umbrella review; behavioral outcomes

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MDPI and ACS Style

Gkintoni, E.; Papachatzi, E.; Efthymiadou, E.; Magriplis, E.; Vantarakis, A. Neurodevelopmental Pathways from Maternal Obesity to Offspring Outcomes: An Umbrella Review of Cognitive and Behavioral Consequences Across Development. Healthcare 2025, 13, 2653. https://doi.org/10.3390/healthcare13202653

AMA Style

Gkintoni E, Papachatzi E, Efthymiadou E, Magriplis E, Vantarakis A. Neurodevelopmental Pathways from Maternal Obesity to Offspring Outcomes: An Umbrella Review of Cognitive and Behavioral Consequences Across Development. Healthcare. 2025; 13(20):2653. https://doi.org/10.3390/healthcare13202653

Chicago/Turabian Style

Gkintoni, Evgenia, Eleni Papachatzi, Erifili Efthymiadou, Emmanuella Magriplis, and Apostolos Vantarakis. 2025. "Neurodevelopmental Pathways from Maternal Obesity to Offspring Outcomes: An Umbrella Review of Cognitive and Behavioral Consequences Across Development" Healthcare 13, no. 20: 2653. https://doi.org/10.3390/healthcare13202653

APA Style

Gkintoni, E., Papachatzi, E., Efthymiadou, E., Magriplis, E., & Vantarakis, A. (2025). Neurodevelopmental Pathways from Maternal Obesity to Offspring Outcomes: An Umbrella Review of Cognitive and Behavioral Consequences Across Development. Healthcare, 13(20), 2653. https://doi.org/10.3390/healthcare13202653

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