Early Risk Factors for ADHD Similar in Boys and Girls

Megan Brooks

December 02, 2013

Despite the well-documented sex difference in the prevalence of attention-deficit/hyperactivity disorder (ADHD), when it comes to early perinatal risk factors, there seems to be little variance between boys and girls, new research suggests.

Contrary to other studies, new results from a population-based, record linkage, case-control study show that low birth weight, post-term pregnancy, low Apgar scores, and fetal distress were not factors for ADHD irrespective of sex.

"Our study is one of the largest population studies on antenatal risk factors published to date, using a robust, reliable data linkage system with only deidentified data, ensuring strict privacy. Importantly, we found that risk associations were generally similar for boys and girls with ADHD," investigators led by Desiree Silva, FRACP, MPH, from Telethon Institute for Child Health Research and School of Pediatrics and Child Health, University of Western Australia in Perth, write.

The study was published online December 2 in Pediatrics.

Highly Heritable

The most common mental health disorder in childhood, ADHD is highly heritable and much more common in boys. Several studies have identified perinatal risk factors for ADHD, but until now, no study has specifically looked at risk factors for boys and girls separately.

The researchers sought to investigate maternal, pregnancy, and newborn risk factors by sex for children prescribed stimulant medication for the treatment of ADHD.

The study included 12,991 children and adolescents with ADHD and 30,071 children without the disorder who acted as controls.

The results showed that factors including low birth weight and post-term pregnancy that had previously been linked to ADHD did not increase risk.

In addition, the investigators note that although birth order is considered a key environmental factor in child development and that being first born has previously been associated with an increased risk for psychiatric disorders such as ADHD, this did not bear out in the fully adjusted model.

They found there was an elevated risk for ADHD in both boys and girls when mothers had a urinary tract infection during pregnancy (odds ratio [OR], 1.37; 95% confidence interval [CI], 1.21 - 1.55 for boys; OR, 1.51; 95% CI, 1.21 - 1.90 for girls) or preeclampsia (OR 1.32; 95% CI, 1.21 - 1.44 for boys; OR, 1.44; 95% CI, 1.22 - 1.70 for girls). Mothers of children with ADHD were also significantly more likely to be younger, single, to have smoked during pregnancy, to have had labor induced, and to have experienced threatened preterm labor.

In girls, oxytocin augmentation (but not induction) emerged as a novel potential protective factor, but the authors caution that this "may be a chance finding."

The researchers note that additional studies "should investigate this association and provide some neurobiological explanation, including whether a reduction in duration of labor is plausible, because it is surprising that such a late intervention as augmentation of labor may potentially have a neuroprotective effect for female births."

Further studies designed to "disentangle possible mechanisms, confounders, and moderators of these risk factors are warranted," they add.

Oxytocin Protective?

Commenting on the study for Medscape Medical News, ADHD researcher Lidy Pelsser, PhD, of Pelsser RED Centrum, Eindhoven, the Netherlands, who was not involved in the research, said she is also wary of the suggestion that oxytocin augmentation may somehow be protective.

It is "very awkward and unlikely: why would there be an effect of oxytocin augmentation but not of oxytocin induction? Further investigation is needed to differentiate among potential explanations of the association, including underlying pregnancy conditions requiring the eventual need to induce/augment the events of labor and delivery associated with induction/augmentation," she said.

Also as noted by the authors, the lack of information on parental diagnosis of ADHD is a key limitation of the study, said Dr. Pelsser.

"Considering the high heritability (79%) of ADHD, it goes without saying that parental information is very important."

In terms of smoking, Dr. Pelsser cautions that it is not possible to determine from this study whether smoking during pregnancy increases the risk for ADHD, only that there is an association between smoking and ADHD.

In general, Dr. Pelsser said she finds it "really frustrating…that we keep on searching in environmental corners where we know the answer will not be found."

In her view, "other environmental corners, like ADHD being triggered by a hypersensitivity to foods," as suggested by a study published in the Lancet in 2011 and reported by Medscape Medical News at that time, are "very promising but sadly enough generally ignored."

The study was supported by the National Health and Medical Research Council. The authors and Dr. Pelsser report no relevant financial relationships.

Pediatrics. Published online December 2, 2013. Abstract

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