Maternal Genes Tied to ADHD Development in Children

By Marilynn Larkin

May 09, 2019

NEW YORK (Reuters Health) - Mothers at high genetic risk for attention-deficit/hyperactivity disorder (ADHD) and other neurodevelopmental disorders may also be at risk for adverse behaviors during pregnancy that could affect their child, according to a recent study.

"Mothers provide their children with genetic information, as well as the prenatal environment. Therefore, it is possible that associations between pregnancy risk factors and neurodevelopmental disorder in the child are not causal, but due to genetic risk shared between mother and child," Dr. Beate Leppert of the University of Bristol, UK told Reuters Health.

"We measured maternal genetic risk for ADHD, autism and schizophrenia, and assessed if these genetic risk factors increase the risk of pregnancy exposures that have been considered risk factors for these disorders," she explained by email.

"We found that a high genetic risk for ADHD in mothers was associated with a range of factors that have been considered risk factors for ADHD in children, such as paracetamol use, heavy metal exposure and infections during pregnancy," she said.

"We want to stress that we assessed the contribution of genetic risk for neurodevelopmental disorders on prenatal factors in the general population - in mothers who do not necessarily present with the disorder but might have subthreshold symptoms," she noted. "Our findings suggest that associations between pregnancy risk factors and child neurodevelopmental disorders are at least partly explained by genetic risk, primarily for ADHD."

Dr. Leppert and colleagues calculated polygenic risk scores (PRSs) for 7,921 mothers (mean age 28.5) with genotype data from the Avon Longitudinal Study of Parents and Children. They also assessed questionnaire data on the mothers' lifestyle and behavior (e.g., smoking, alcohol consumption, body mass index); use of nutritional supplements and medications in pregnancy (e.g., acetaminophen, iron, zinc, folic acid, and vitamins); illnesses (e.g., diabetes, hypertension, rheumatism, psoriasis, depression); and perinatal factors (e.g., birth weight, preterm birth, and cesarean delivery).

As reported online May 1 in JAMA Psychiatry, the ADHD PRS was associated with multiple prenatal factors, including infections (odds ratio, 1.11), acetaminophen use during late pregnancy (OR, 1.11), lower blood levels of mercury, and higher blood levels of cadmium.

By contrast, there was little evidence to suggest associations between the ASD or SCZ PRS and prenatal factors, or between any of the PRSs and adverse birth events. The results were upheld in sensitivity analyses.

Summing up, the authors state, "these findings highlight the need to carefully account for potential genetic confounding and triangulate evidence from different approaches when assessing the effects of prenatal exposures on neurodevelopmental disorders in offspring."

Dr. Leppert said, "Further studies using a combination of causally informative study designs are required to causally assess the risk of prenatal factors. This can include Mendelian randomization, family, twin and IVF studies and replication in other large cohorts."

"Determining which exposures are truly causal will identify potential intervention targets to reduce the burden of neurodevelopmental disorders," she concluded.

Psychiatric physician Dr. Rupali Chadha, Chief of Medical Staff at Metropolitan State Hospital in Norwalk, California, told Reuters Health by email, "This is the first study that is showing this maternal genetic link coupled with these environmental factors resulting in an illness in her child later. Follow-up studies are always needed to replicate results in an initial study."

Clinically, said Dr. Chadha, who was not involved in the study, "I would change my practice only to inform mothers of these suspected links. I would educate them that this is one study. And they'd have to have the risk alleles in order to have the environmental factors 'switch' them on."

"That being said, I may recommend avoiding (acetaminophen) and sick contacts - a good practice anyhow," she noted. "As of now, we aren't genetically screening for every risk allele known to us, but this highlights the future of perinatal care."


JAMA Psychiatry 2019.