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Obesity in women of reproductive age has emerged as one of the main risk factors associated with neonatal complications and long-term neuropsychiatric consequences in offspring, including attention-deficit/hyperactivity disorder.

Research has also linked pregestational diabetes and gestational diabetes mellitus (GDM) to an increased risk for ADHD in offspring. Now, an observational study of 1,036 singleton births at one hospital between 1998 and 2008 suggests that in the presence of GDM, maternal obesity combined with excessive weight gain during pregnancy may be jointly associated with increased risk of offspring ADHD. The median follow-up was 17.7 years.

Maternal obesity was independently associated with ADHD (adjusted hazard ratio, 1.66), but excessive weight gain during pregnancy and maternal overweight were not, reported Verónica Perea, MD, renova zay flama merkezi adana PhD, of the Hospital Universitari Mútua de Terrassa, Barcelona, and colleagues in the Journal of Clinical Endocrinology & Metabolism.

However, in women with pregestation obesity who gained more weight than recommended by the National Academy of Medicine (NAM), the risk of offspring ADHD was higher, compared with women of normal weight whose pregnancy weight stayed within NAM guidelines (adjusted hazard ratio, 2.13; 95% confidence interval).

“The results of this study suggest that the negative repercussions of excessive weight gain on children within the setting of a high-risk population with GDM and obesity were not only observed during the prenatal period but also years later with a development of ADHD,” the researchers wrote.

The study also showed that when maternal weight gain did not exceed NAM guidelines, maternal obesity was no longer independently associated with ADHD in offspring (aHR, 1.36; 95% CI). This finding conflicts with earlier studies focusing primarily on the role of pregestational maternal weight, the researchers said. A 2018 nationwide Finnish cohort study in newborns showed an increased long-term risk of ADHD in those born to women with GDM, compared with the nondiabetic population (HR, 1.15; 95% CI). This long-term risk of ADHD increased in the presence of pregestational obesity (HR, 1.64).

Similarly, evidence from systematic reviews and meta-analyses has demonstrated that antenatal lifestyle interventions to prevent excessive weight gain during pregnancy were associated with a reduction in adverse pregnancy outcomes. However, evidence on offspring mental health was lacking, especially in high-risk pregnancies with gestational diabetes, the study authors said.

Although causal inferences can’t be drawn from the current observational study, “it seems that the higher risk [of ADHD] observed would be explained by the role of gestational weight gain during the antenatal period,” Perea said in an interview. Importantly, the study highlights a window of opportunity for promoting healthy weight gain during pregnancy, Perea said. “This should be a priority in the current management of gestation.”

Fatima Cody Stanford, MD, MPH, an associate professor of medicine and pediatrics at Harvard Medical School, Boston, agreed. “I think one of the key issues is that there’s very little attention paid to how weight gain is regulated during pregnancy,” she said in an interview. On many other points, however, Stanford, who is a specialist in obesity medicine at Massachusetts General Hospital Weight Center, did not agree.

The association between ADHD and obesity has already been well established by a 2019 meta-analysis and systematic review of studies over the last 10 years, she emphasized. “These studies were able to show a much stronger association between maternal obesity and ADHD in offspring because they were powered to detect differences.”

The current study does not say “anything new or novel,” Stanford added. “Maternal obesity and the association with an increased risk of ADHD in offspring is the main issue. I don’t think there was any appreciable increase when weight gain during pregnancy was factored in. It’s mild at best.”

Eran Bornstein, MD, vice-chair of obstetrics and gynecology at Lenox Hill Hospital, New York, expressed a similar point of view. Although the study findings “add to the current literature,” they should be interpreted “cautiously,” Bornstein said in an interview.

The size of the effect on ADHD risk attributable to maternal weight gain during pregnancy “was not clear,” he said. “Cohort studies of this sort are excellent for finding associations which help us generate the hypothesis, but this doesn’t demonstrate a cause and effect or a magnitude for this effect.”

Physicians should follow cumulative data suggesting that maternal obesity is associated with a number of pregnancy complications and neonatal outcomes in women with and without diabetes, Bornstein suggested. “Optimizing maternal weight prior to pregnancy and adhering to recommendations regarding weight gain has the potential to improve some of these outcomes.”

Treating obesity prior to conception mitigates GDM risk, agreed Stanford. “The issue,” she explained, “is that all of the drugs approved for the treatment of obesity are contraindicated in pregnancy and lifestyle modification fails in 96% of cases, even when there is no pregnancy.” Drugs such as metformin are being used off-label to treat obesity and to safely manage gestational weight gain, she said. “Those of us who practice obesity medicine know that metformin can be safely used throughout pregnancy with no harm to the fetus.”

This study was partially funded by Fundació Docència i Recerca MútuaTerrassa. Perea and study coauthors reporting have no conflicts of interest. Stanford disclosed relationships with Novo Nordisk, Eli Lilly, Boehringer Ingelheim, Gelesis, Pfizer, Currax, and Rhythm. Bornstein reported having no conflicts of interest.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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