Steroids in Pregnancy May Heighten Autism, ADHD Risk in Child

Children exposed to glucocorticoids prenatally may have an increased risk of developing autism, attention-deficit/hyperactivity disorder (ADHD), and other mood-related conditions, according to a study published in JAMA Network Open.

Researchers from Aarhus University in Aarhus, Denmark, analyzed data from over 1 million births in Denmark from 1999 to 2016. Previous studies linking the drugs to mental disorders are limited, which prompted researchers to fill evidence gaps.

Children who were exposed to glucocorticoids in utero were compared with those who were not. Some mothers had taken glucocorticoids to reduce the risk for preterm delivery, while others took them to help manage autoimmune or inflammatory disorders.

The findings highlight the importance of balancing the benefits of taking glucocorticoids during pregnancy with potential risks, said Kristina Laugesen, MD, PhD, a physician and researcher in the Department of Clinical Epidemiology at Aarhus University and Aarhus University Hospital, and lead author of the study.

“Adverse effects of glucocorticoids and how to minimize use is an ongoing debate among clinicians,” Laugesen said. “The drug has many beneficial effects…but we need to focus on reducing prescribing by increasing awareness.”

Children exposed to steroids because their mothers were at risk for preterm delivery had a 50% higher risk for autism spectrum disorders and a 30% higher risk for ADHD than children who were not exposed but whose mothers were also at risk for preterm delivery.

Researchers also observed a 50% higher risk for mood, anxiety, and stress-related disorders (risk ratio, 1.5; 95% CI, 1.1-2.0).

Children whose mothers had an autoimmune or inflammatory disorder and were exposed to steroids had from 30% to 40% higher risk of developing the mental disorders than children born to similar mothers but who were not exposed to the drugs.

Laugesen said clinicians should take note that the differences were modest in risk for disorders between children exposed to steroids and those who were not.

Mark Clapp, MD, MPH, a maternal-fetal medicine specialist at Massachusetts General Hospital in Boston, said prescribing glucocorticoids is commonplace for pregnant women at risk for preterm labor, especially when administered before 34 weeks of pregnancy. Steroids increase blood sugar, putting the neonate at risk of developing hypoglycemia.

“Some hypothesize there may be long-term effects for the neonate for being hypoglycemic, though this association is not well understood, and the data are mixed.”

Clapp said most clinicians make the call to administer steroids to mothers at risk for preterm delivery using shared decision-making.

“This means we should counsel the patients on all the information that we have, acknowledge places of ambiguity or lack of clarity about the best way forward, and then work with the patient to make the best decision,” Clapp said.

Both Clapp and Laugesen said further research is needed to help physicians decide the best treatment option for their patients.

“The findings are important to encourage more research on the topic,” Laugesen said. “For instance, increased surveillance and continued reevaluation of the risk of preterm birth may decrease use of glucocorticoids. Concerning women with autoimmune disorders, alternative medication may be an option, but more research is needed on the safety of these other medications.”

One study author reported employment at Novo Nordisk. No other disclosures were reported.