Genetic factors impacting birth weight and neurodivergence

Genetic factors impacting birth weight and neurodivergence | Image Credit: © kieferpix - © kieferpix - stock.adobe.com.

According to a recent study published in JAMA Network Open, neurodevelopmental conditions (NDCs) are impacted by low birth weight, and this link is associated with genetic conditions.

About 18% of individuals in the United States present with NDCs, including autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID). Genetic and nonshared environmental factors have been linked to NDCs, with low birth weight being linked to autism, ADHD, and ID.

Investigators have not determined if there is an independent association between low birth weight and NDCs, or if other factors such as genetic susceptibility impact this association. However, this association can be analyzed using a twin co-control design with dizygotic and monozygotic twins, which share 50% and 100% of their genome respectively.

To determine how genetic conditions influence the association between low birth weight and NDCs, investigators conducted a study incorporating a co-twin control design. Assessment occurred from August 2011 to March 2022.

Eligibility criteria included 1 or both twins having a positive NDC screening result or typical development. Zygosity was, “determined using a panel of 48 single-nucleotide polymorphisms.” Diagnostic assessment was accomplished using Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria.

The assessment occurred during a 2-and-a-half-day clinic visit. Tools used for assessment include the Autism Diagnostic Interview–Revised, Autism Diagnostic Observation Schedule–2,the Structured Clinical Interview for DSM-IV, the Diagnostic Interview for ADHD in Adults, and the Adaptive Behavior Assessment System–2.

The Social Responsiveness Scale–2 was used to evaluate autistic traits, measured on a 4-point Likert scale. A 3-point Likert scale was used when measuring ADHD traits, and intelligence quotient (IQ) ratings were measured using a Wechsler Intelligence Scale based on participant age.

A questionnaire from the original study gathered prenatal, perinatal, and postnatal data. Questionnaires were completed during participant visit and validated against medical registry data. A significant correlation was found between birth weight information and medical record data.

There were 393 participants included in the analysis, 230 of which were monozygotic same-sex twins and 159 dizygotic twins. Participants were aged a mean 15 years, and 47.1% were female and 52.9% male. 

An ADHD diagnosis was made in 28% of participants, an autism diagnosis in 23.4%, an ID diagnosis in 5.1%, another NDC diagnosis in 16.8%, and another psychiatric disorder diagnosis in 26%. A birth weight under 2 kg was recorded in 19.8% of patients, and a birth weight of under 2.5 kg in 45.3% The average birth weight was 2.49 kg for monozygotic twins and 2.55 kg for dizygotic twins.

An association was made between increased birth weight and reduced autistic traits, but this association was not found with ADHD traits or IQ.This association remained across monozygotictwin pairs, and these individuals were also seen with an association between higher birth weight and higher IQ ratings and fewer ADHD traits.

Higher IQ ratings, along with lower ADHD and autism traits ratings, were also found in older individuals. Decreased odds ratios of autism and ID were also found in individuals with increased birth weight. The association with autism remained in monozygotic twin pairs.

As associations were only found among monozygotic twin pairs, investigators concluded there is a genetic confounding of the association between birth weight and NDCs. Investigators recommended future studies on the biological mechanisms underlying this association.

Reference

Isaksson J, Ruchkin V, Ljungström T, Bölte S. Evaluation of birth weight and neurodevelopmental conditions among monozygotic and dizygotic twins. JAMA Netw Open. 2023;6(6):e2321165. doi:10.1001/jamanetworkopen.2023.21165