TY - JOUR
T1 - Is maternal diabetes during pregnancy associated with neurodevelopmental, cognitive and behavioural outcomes in children?
T2 - Insights from individual participant data meta-analysis in ten birth cohorts
AU - Pretorius, Rachelle A.
AU - Avraam, Demetris
AU - Guxens, Mònica
AU - Julvez, Jordi
AU - Harris, Jennifer R.
AU - Nader, Johanna Thorbjornsrud
AU - Cadman, Tim
AU - Elhakeem, Ahmed
AU - Strandberg-Larsen, Katrine
AU - Marroun, Hanan El
AU - Defina, Serena
AU - Yang, Tiffany C.
AU - McEachan, Rosie
AU - Wright, John
AU - Ibarluzea, Jesús
AU - Santa-Marina, Loreto
AU - Delgado, Juana Mari
AU - Rebagliato, Marisa
AU - Charles, Marie Aline
AU - Vainqueur, Chloe
AU - Maritano, Silvia
AU - Zugna, Daniela
AU - Yuan, Wen Lun
AU - Heude, Barbara
AU - Huang, Rae Chi
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85217357252&partnerID=8YFLogxK
U2 - 10.1186/s12887-024-05365-y
DO - 10.1186/s12887-024-05365-y
M3 - Article
C2 - 39885386
AN - SCOPUS:85217357252
SN - 1471-2431
VL - 25
SP - 76
JO - BMC Pediatrics
JF - BMC Pediatrics
IS - 1
M1 - 76
ER -