The role of obstetric adversities in neurodevelopmental conditions: A sibling study

Neurodevelopmental conditions (NDC) are highly heritable. Obstetric complications (OC) have been studied as potential predictors for NDC, although results are inconsistent. Inconsistencies might be related to biases such as family confounders. While some studies using sibling and twin designs have examined the association between OC and NDC, this body of research remains limited, and findings to date remain inconsistent. We used a case-control sibling study including children aged 6-17 years across five groups: those diagnosed with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), co-occurring ASD + ADHD, their unaffected siblings and a comparison group without NDC. For analytic purposes, we created a combined NDC group including all individuals with ASD, ADHD or both. Participants were recruited between 2021 and 2022 from a tertiary hospital in Spain. We examined the association of NDC and OC using single predictors and cumulative OC. The study adheres to the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. A total of 238 participants were included (NDC = 117, unaffected siblings = 82, comparison group = 39). We found that NDC individuals showed more neonatal complications than the comparison group (β = 1.73, 95% CI = 1.00-2.98, p = 0.04), which remained significant in the sibling analysis (β = 1.43, 95% CI = 1.02-2.00, p = 0.04). This study supports that the cumulative neonatal complications, rather than specific factors, are associated with increased likelihood of being diagnosed with NDC, beyond familial confounding. Results highlight the neonatal period as a relevant window of vulnerability.Lay AbstractThe role of complications during pregnancy in neurodevelopmental disorders: a sibling studyThis study examined the association between complications during pregnancy and autism, attention-deficit/hyperactivity disorder and the combination of both conditions. We compared children with these conditions and their siblings, as well as a group comparison without diagnosed neurodevelopmental disorders. We gathered information through parents' interviews. We found that children with autism or attention-deficit/hyperactivity disorder presented more problems in the first 4 weeks of the child's life than their siblings and the group of comparison. We did not find that children with these conditions present more complications during pregnancy. In addition, we observed that the probability of being diagnosed with these conditions is increased due to cumulative problems rather than specific problems.