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

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• dc.contributor.author Pretorius, Rachelle A.
• dc.contributor.author Guxens Junyent, Mònica
• dc.contributor.author Júlvez Calvo, Jordi
• dc.contributor.author Huang, Rae-Chi
• dc.date.accessioned 2025-04-08T06:13:00Z
• dc.date.available 2025-04-08T06:13:00Z
• dc.date.issued 2025
• dc.description.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.
• dc.description.sponsorship 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Pretorius RA, Avraam D, Guxens M, Julvez J, Harris JR, Nader JT, et al. 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 Pediatr. 2025 Jan 30;25(1):76. DOI: 10.1186/s12887-024-05365-y
• dc.identifier.doi http://dx.doi.org/10.1186/s12887-024-05365-y
• dc.identifier.issn 1471-2431
• dc.identifier.uri http://hdl.handle.net/10230/70103
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof BMC Pediatr. 2025 Jan 30;25(1):76
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/733206
• dc.rights © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Attention deficient hyperactive disorder
• dc.subject.keyword Autism spectrum disorder
• dc.subject.keyword Behavioural
• dc.subject.keyword Cognitive
• dc.subject.keyword Externalising problems
• dc.subject.keyword Gestational diabetes mellitus
• dc.subject.keyword Neurodevelopmental
• dc.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
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion