Perinatal and familial factors associated with intellectual disability/global developmental delay: A multicenter frequency-matched case–control study

Intellectual disability (ID) and global developmental delay (GDD) are neurodevelopmental disorders that place significant lifelong burdens on affected individuals and families. However, modifiable perinatal risk factors remain underexplored in multicenter Chinese populations. In this multicenter, frequency-matched case–control study, we aimed to identify independent familial and perinatal risk factors for ID/GDD and to standardize terminology for language impairment–related comorbidities. We recruited 412 children with ID/GDD and 824 developmentally normal controls from 15 tertiary centers between 2020 and 2022. Cases were diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and standardized developmental assessments; controls had normal developmental screening results. Family history was defined as first-degree relatives (parents or siblings) with ID, GDD, autism spectrum disorder, epilepsy, or clinically documented learning disorders. Perinatal exposures – including gestational hypertension, gestational diabetes mellitus, cesarean delivery, prolonged labor, meconium-stained amniotic fluid, neonatal asphyxia, postpartum hemorrhage, puerperal infection, and parity – were collected using predefined definitions. Unconditional logistic regression was performed, adjusting for age category, sex, residence, and prespecified covariates (family history, maternal age, and gestational age). Six independent risk factors were identified: first-degree family history (adjusted odds ratio [aOR]: 2.12; 95% confidence interval [CI]: 1.13–3.98), gestational hypertension (aOR: 1.76; 95% CI: 1.01–3.05), cesarean delivery (aOR: 1.85; 95% CI: 1.04–3.29), prolonged labor (aOR: 2.21; 95% CI: 1.11–4.40), neonatal asphyxia (aOR: 3.67; 95% CI: 1.20–11.20), and postpartum hemorrhage (aOR: 2.51; 95% CI: 1.01–6.23). Other factors, such as parity ≥2, gestational diabetes mellitus, meconium-stained amniotic fluid, and puerperal infection, were not significantly associated with ID/GDD after adjustment. Overall, 62.6% of cases had at least 1 comorbidity. These findings indicate that modifiable perinatal complications – especially prolonged labor, neonatal asphyxia, postpartum hemorrhage, and maternal hypertension – along with familial predisposition, are associated with an increased risk of ID/GDD. Enhanced obstetric surveillance, timely neonatal resuscitation, and structured family history assessment may improve early risk stratification and prevention strategies.