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Journal article
Is maternal diabetes during pregnancy associated with neurodevelopmental, cognitive and behavioural outcomes in children? Insights from individual participant data meta-analysis in ten birth cohorts
BMC pediatrics, Vol.25(1), 76
2025
PMID: 39885386
Abstract
Background
Growing evidence shows that dysregulated metabolic intrauterine environments can affect offspring’s neurodevelopment and behaviour. However, the results of individual cohort studies have been inconsistent. We aimed to investigate the association between maternal diabetes before pregnancy and gestational diabetes mellitus (GDM) with neurodevelopmental, cognitive and behavioural outcomes in children.
Methods
Harmonised data from > 200 000 mother-child pairs across ten birth cohorts in Europe and Australia were available. Mother-child pairs were included for analysis to determine whether GDM was recorded (yes or no) and whether at least one neurodevelopmental, cognitive and behavioural outcome was available in children aged 3 to 13 years. Confounder-adjusted regression models were used to estimate associations between maternal diabetes and child outcomes using two-stage individual participant data (IPD) meta-analysis. Model 1 included a crude estimate. The full adjustment model (model 2) included adjustment for child sex, maternal age, pre-pregnancy BMI, pregnancy weight gain, maternal smoking during pregnancy, plurality, parity and maternal education.
Results
Children (aged 7–10 years) born to mothers with GDM had higher attention-deficient hyperactive disorder (ADHD) symptoms compared to non-exposed controls (model 2, regression coefficient (β) 3.67 (95% CI 1.13, 6.20), P = 0.001). Moreover, children (aged 4–6 years) born to mothers with GDM exhibited more externalising problems than those born to mothers without GDM (model 2, β 2.77 (95% CI 0.52, 5.02), P = 0.01). A pre-existing maternal history of type 1 and type 2 diabetes mellitus was associated with ADHD symptoms at 4–6 years (model 1, β 8.82 (95% CI 2.21, 15.45, P = 0.009) and β 7.90 (95% CI 0.82, 14.98, P = 0.02), respectively). The association was no longer apparent in further adjustments.
Conclusions
This study found that children between 4 - 6 and 7–10 years of age born to mothers with GDM have a greater likelihood of developing externalising problems and ADHD symptoms, respectively. Externalising problems often co-exist with ADHD symptoms and precede formal ADHD diagnosis. Overall, this large-scale multi-cohort study suggested that a dysregulated metabolic environment during pregnancy may contribute to ADHD symptoms and externalising problems in young children.
Details
- Title
- Is maternal diabetes during pregnancy associated with neurodevelopmental, cognitive and behavioural outcomes in children? Insights from individual participant data meta-analysis in ten birth cohorts
- Authors/Creators
- Rachelle A Pretorius - Murdoch University, School of Medical, Molecular and Forensic SciencesDemetris Avraam - Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, DenmarkMònica Guxens - Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Centre, Rotterdam, The NetherlandsJordi Julvez - Clinical and Epidemiological Neuroscience Group (NeuroÈpia), Institut d'Investigació Sanitària Pere Virgili (IISPV), 43204 Reus (Tarragona), Catalonia, Barcelona, SpainJennifer R Harris - Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, NorwayJohanna Thorbjornsrud Nader - Department of Genetics and Bioinformatics, Division of Health Data and Digitalisation, Norwegian Institute of Public Health, Oslo, NorwayTim Cadman - UMCG Genetics Department, Genetics Department, University Medical Centre Groningen, GCC - Genomic Coordination Centre), Groningen, The NetherlandsAhmed Elhakeem - Population Health Science, Bristol Medical School, University of Bristol, Bristol, UKKatrine Strandberg-Larsen - Section of Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen, DenmarkHanan El Marroun - Erasmus University RotterdamSerena Defina - The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The NetherlandsTiffany C Yang - Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UKRosie McEachan - Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UKJohn Wright - Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UKJesús Ibarluzea - Biogipuzkoa Health Research Institute, Environmental Epidemiology and Child Development San Sebastian, Madrid, SpainLoreto Santa-Marina - Centro de Investigación Biomédica en Red de Epidemiología y Salud PúblicaJuana Mari Delgado - Epidemiology and Environmental Health Joint Research Unit, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region, FISABIO-Public Health, FISABIO-Universitat Jaume I-Universitat de València, Valencia, SpainMarisa Rebagliato - Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, SpainMarie-Aline Charles - Joint unit Elfe, Ined, Inserm, Aubervilliers, 93322, FranceSilvia Maritano - Piedmont Reference Center for Epidemiology and Cancer PreventionChloe Vainqueur - Université Paris Cité and Université Sorbonne Paris Nord, INRAE, Centre for Research in Epidemiology and StatisticS (CRESS), Inserm, Paris, F-75004, FranceDaniela Zugna - Cancer Epidemiology Unit, Medical Science Department, University of Turin and CPO Piemonte, Via Santena 7, Turin, 10126, ItalyWen Lun Yuan - Université Paris Cité and Université Sorbonne Paris Nord, INRAE, Centre for Research in Epidemiology and StatisticS (CRESS), Inserm, Paris, F-75004, FranceBarbara Heude - Université Paris Cité and Université Sorbonne Paris Nord, INRAE, Centre for Research in Epidemiology and StatisticS (CRESS), Inserm, Paris, F-75004, FranceRae-Chi Huang - The Kids Research Institute Australia
- Publication Details
- BMC pediatrics, Vol.25(1), 76
- Publisher
- BioMed Central Ltd unless otherwise stated. Part of Springer Nature.; LONDON
- Number of pages
- 15
- Grant note
- European Union's Horizon 2020 Research and Innovation Programme: 733206
\LifeCycle is a 5-year research project that is funded through the European Union's Horizon 2020 Research and Innovation Programme (grant agreement no. 733206). Cohort-specific funding is provided in Supplementary Text 2.
- Identifiers
- 991005741592207891
- Copyright
- © The Author(s) 2025.
- Murdoch Affiliation
- School of Medical, Molecular and Forensic Sciences
- Language
- English
- Resource Type
- Journal article
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- Domestic collaboration
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- Citation topics
- 1 Clinical & Life Sciences
- 1.72 Obstetrics & Gynecology
- 1.72.182 Maternal-Fetal Health
- Web Of Science research areas
- Pediatrics
- ESI research areas
- Clinical Medicine