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
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 p...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12887-024-05365-y |
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| author | Rachelle A. Pretorius Demetris Avraam Mònica Guxens Jordi Julvez Jennifer R. Harris Johanna Thorbjornsrud Nader Tim Cadman Ahmed Elhakeem Katrine Strandberg-Larsen Hanan El Marroun Serena Defina Tiffany C. Yang Rosie McEachan John Wright Jesús Ibarluzea Loreto Santa-Marina Juana Mari Delgado Marisa Rebagliato Marie-Aline Charles Chloe Vainqueur Silvia Maritano Daniela Zugna Wen Lun Yuan Barbara Heude Rae-Chi Huang |
| author_facet | Rachelle A. Pretorius Demetris Avraam Mònica Guxens Jordi Julvez Jennifer R. Harris Johanna Thorbjornsrud Nader Tim Cadman Ahmed Elhakeem Katrine Strandberg-Larsen Hanan El Marroun Serena Defina Tiffany C. Yang Rosie McEachan John Wright Jesús Ibarluzea Loreto Santa-Marina Juana Mari Delgado Marisa Rebagliato Marie-Aline Charles Chloe Vainqueur Silvia Maritano Daniela Zugna Wen Lun Yuan Barbara Heude Rae-Chi Huang |
| author_sort | Rachelle A. Pretorius |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-0691b38da45b4e458e3d2063e653ff3a |
| institution | Kabale University |
| issn | 1471-2431 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | BMC Pediatrics |
| spelling | doaj-art-0691b38da45b4e458e3d2063e653ff3a2025-02-02T12:42:51ZengBMCBMC Pediatrics1471-24312025-01-0125111510.1186/s12887-024-05365-yIs maternal diabetes during pregnancy associated with neurodevelopmental, cognitive and behavioural outcomes in children? Insights from individual participant data meta-analysis in ten birth cohortsRachelle A. Pretorius0Demetris Avraam1Mònica Guxens2Jordi Julvez3Jennifer R. Harris4Johanna Thorbjornsrud Nader5Tim Cadman6Ahmed Elhakeem7Katrine Strandberg-Larsen8Hanan El Marroun9Serena Defina10Tiffany C. Yang11Rosie McEachan12John Wright13Jesús Ibarluzea14Loreto Santa-Marina15Juana Mari Delgado16Marisa Rebagliato17Marie-Aline Charles18Chloe Vainqueur19Silvia Maritano20Daniela Zugna21Wen Lun Yuan22Barbara Heude23Rae-Chi Huang24Nutrition & Health Innovation Research Institute, Edith Cowan UniversityDepartment of Public Health, Policy and Systems, University of LiverpoolISGlobal in BarcelonaISGlobal in BarcelonaCentre for Fertility and Health, Norwegian Institute of Public HealthDepartment of Genetics and Bioinformatics, Division of Health Data and Digitalisation, Norwegian Institute of Public HealthSection of Epidemiology, Department of Public Health, University of CopenhagenPopulation Health Science, Bristol Medical School, University of BristolSection of Epidemiology, Department of Public Health, University of CopenhagenDepartment of Psychology, Education and Child Studies, Erasmus School of Social and Behavioural Sciences, Erasmus University RotterdamDepartment of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical CentreBradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation TrustBradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation TrustBradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation TrustBiogipuzkoa Health Research Institute, Environmental Epidemiology and Child Development San SebastianSpanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos IIIDepartment of Medicine, Faculty of Health Sciences, Universitat Jaume IDepartment of Medicine, Faculty of Health Sciences, Universitat Jaume IUniversité Paris Cité and Université Sorbonne Paris Nord, INRAE, Centre for Research in Epidemiology and StatisticS (CRESS)Université Paris Cité and Université Sorbonne Paris Nord, INRAE, Centre for Research in Epidemiology and StatisticS (CRESS)Cancer Epidemiology Unit, Medical Science Department, University of Turin and CPO PiemonteCancer Epidemiology Unit, Medical Science Department, University of Turin and CPO PiemonteUniversité Paris Cité and Université Sorbonne Paris Nord, INRAE, Centre for Research in Epidemiology and StatisticS (CRESS)Université Paris Cité and Université Sorbonne Paris Nord, INRAE, Centre for Research in Epidemiology and StatisticS (CRESS)Nutrition & Health Innovation Research Institute, Edith Cowan UniversityAbstract 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.https://doi.org/10.1186/s12887-024-05365-yGestational diabetes mellitusAttention deficient hyperactive disorderAutism spectrum disorderNeurodevelopmentalCognitiveBehavioural |
| spellingShingle | Rachelle A. Pretorius Demetris Avraam Mònica Guxens Jordi Julvez Jennifer R. Harris Johanna Thorbjornsrud Nader Tim Cadman Ahmed Elhakeem Katrine Strandberg-Larsen Hanan El Marroun Serena Defina Tiffany C. Yang Rosie McEachan John Wright Jesús Ibarluzea Loreto Santa-Marina Juana Mari Delgado Marisa Rebagliato Marie-Aline Charles Chloe Vainqueur Silvia Maritano Daniela Zugna Wen Lun Yuan Barbara Heude Rae-Chi Huang 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 Gestational diabetes mellitus Attention deficient hyperactive disorder Autism spectrum disorder Neurodevelopmental Cognitive Behavioural |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Gestational diabetes mellitus Attention deficient hyperactive disorder Autism spectrum disorder Neurodevelopmental Cognitive Behavioural |
| url | https://doi.org/10.1186/s12887-024-05365-y |
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