Evaluation of Birth Weight and Neurodevelopmental Conditions Among Monozygotic and Dizygotic Twins

Key Points Question After adjustment for genetic factors, is birth weight associated with neurodevelopmental conditions? Findings In this case-control study of 393 twins in Sweden, the twin with a lower birth weight in monozygotic twin pairs, but not dizygotic pairs, had more autism and attention-deficit/hyperactivity disorder (ADHD) symptoms, lower IQ ratings, and higher odds of having a diagnosis of autism and ADHD compared with their co-twin. Meaning These findings suggest that birth weight contributes to neurodevelopmental conditions when adjusting for genetic factors. This case-control study estimates the associations between birth weight and neurodevelopmental conditions, such as autism, attention-deficit/hyperactivity disorder, and intellectual disability, among monozygotic and dizygotic twins. Importance Low birth weight is associated with an increased likelihood of neurodivergence and neurodevelopmental conditions (NDCs) such as autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. However, it is unclear whether birth weight contributes independently to NDCs or whether the association is predominantly driven by genetic predisposition. Objective To estimate the associations between birth weight and dimensional (trait) and categorical (diagnoses) NDC outcomes, while adjusting for genetic risks. Design, Setting, and Participants A co-twin design was applied to this case-control study conducted in Sweden.Diagnostic assessments were conducted between August 2011 and March 2022, within the Roots of Autism and ADHD Twin Study in Sweden (RATSS) during a 2.5-day participant visit to the clinic. The RATSS sample comprised phenotyped monozygotic and dizygotic twins enriched for NDCs. Data analysis was conducted in November 2022. ExposureBirth weight. Main Outcomes and Measures Categorical and dimensional operationalizations of autism, ADHD, and intellectual disability were assessed. Generalized estimating equation models were fitted across and within twin pairs. Results The study sample included 393 twins: 230 were monozygotic and 159 were dizygotic (zygosity was unknown for 4). Their median age was 15 (range, 8-37) years. There were 185 female participants (47.1%) and 208 male participants (52.9%). Across twin pairs, higher birth weight was associated with fewer autistic traits (unstandardized beta [B],-5.51 [95% CI, -10.09 to -0.94]) and lower odds of autism diagnosis (OR, 0.63 [95% CI, 0.45 to 0.88]) and intellectual disability (OR, 0.42 [95% CI, 0.19 to 0.92]). Within pairs, the association between birth weight and dimensional autism (B, -17.35 [95% CI, -28.66 to -6.04]) and categorical autism (OR, 0.02 [95% CI, 0.001 to 0.42]) remained among monozygotic pairs but not dizygotic pairs. In addition, higher birth weight was associated with lower odds of ADHD diagnosis (OR, 0.003 [95% CI, 0 to 0.70]), fewer ADHD traits (B, -0.25 [95% CI, -0.39 to -0.11]), and higher IQ ratings (B, 7.43 [95% CI, 1.05 to 13.82]) among monozygotic twins. Conclusions and Relevance The findings of this co-twin study suggest an association between low birth weight and NDCs, but they also acknowledge the importance of genetics because the associations observed were only statically significant among monozygotic twins. It is of pivotal importance to facilitate early identification of factors contributing to fetal growth restriction to minimize detrimental outcomes.