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Prenatal exposure to corticosteroids was associated with increased rates of mental and behavioral disorders in childhood, according to a Finnish registry study.

Among 670,097 children, the risk for developing a mental or behavioral disorder in early childhood was modestly higher for those whose mothers took corticosteroids in pregnancy compared with unexposed kids (adjusted hazard ratio 1.33, 95% CI 1.26-1.41, P<0.001), reported Katri Räikkönen, PhD, of the University of Helsinki, and colleagues.

In an analysis of 241,621 sibling pairs within this population, siblings exposed to maternal prenatal corticosteroids also had a significantly increased risk for developing mental or behavioral disorders versus unexposed siblings (HR 1.38, 95% CI 1.21-1.58, P<0.001), they wrote in .

The risk was significantly higher for exposed versus unexposed children when restricting the analysis to infants born full term (HR 1.47, 95% CI 1.36-1.69, P<0.001), but not among children born preterm (HR 1.00, 95% CI 0.92-1.09, P=0.97), they added.

Together, the findings suggest "unmeasured familiar confounding did not explain these associations," and that corticosteroids "may not pose a risk for mental and behavioral disorders independent of complications and illnesses related to preterm birth," Räikkönen and colleagues wrote. "The risk associated with treatment exposure appeared to be comparable in magnitude to the risk of key covariates, such as maternal smoking during pregnancy."

The American College of Obstetricians and Gynecologists (ACOG) for women with threatened late preterm birth and women undergoing full-term elective cesarean delivery, which translates to more than 10% of births, noted Sara B. DeMauro, MD, of the University of Pennsylvania in Philadelphia, in an

Prior studies have shown prenatal exposure to corticosteroids to be associated with fetal development, with downstream cardiovascular, metabolic, endocrine, and neurologic outcomes, DeMauro added.

However, research has also suggested the "abnormal pregnancy events that lead clinicians to administer steroids also predispose the exposed children to adverse cognitive outcomes, potentially through similar pathways of fetal programming," DeMauro commented.

Notably, fewer than 40% of preterm children in this study were exposed to prenatal corticosteroids and the authors did not report how many infants born very preterm (<32 weeks) were exposed, raising the possibility that the infants who needed this treatment the most did not receive it, DeMauro said.

On the other hand, among the fewer than 45% of infants who were exposed and delivered at term, "minor short-term benefit may have been outweighed by significant longer-term risks," she wrote.

"Although benefits of this therapy outweigh risks in the most vulnerable infants, this may not be true for all infants," she concluded. "Recommendations to administer this therapy to broader populations of pregnant women may need to be reexamined until sufficient safety data, particularly among more mature infants, are available."

For the study, researchers linked registry data for children born 2006-2017 in Finland who survived the first year of life. The birth register did not include data on the number or timing of treatments, although Finnish national guidelines recommended 12 mg betamethasone administered twice, 24 hours apart, up to 34 weeks until 2009 and then up to 34 weeks and 6 days after 2009.

The data were controlled for infant characteristics such as birth year, admission to the neonatal ICU, and weight and gestational age, as well as maternal characteristics (delivery mode, smoking, gestational diabetes, and mental health disorders).

In total, 14,868 children (46.1% female) were exposed to corticosteroids in utero, of which 6,730 (45.27%) were born full term. In contrast, 655,229 children (48.9% female) were not exposed, of which 96.88% were born at term. The cohort was followed up for a median 5.8 years.

Overall, the incidence of any mental and behavioral disorder was significantly higher for the treatment-exposed cohort than the unexposed cohort (12.01% vs 6.45%; 95% CI 5.04%-6.19%, P<0.001), and in term-born children (8.89% vs 6.31%; 95% CI 1.92%-3.29%, P<0.001), the authors reported.

Although the risk was not significantly different among the cohort of preterm-born infants, the incidence of mental or behavioral disorder diagnoses was significantly higher among preterm-born children exposed versus unexposed (14.59% vs 10.71%; 95% CI 2.95%-4.87%, P<0.001), they added.

Mental or behavioral disorders were diagnosed a median 1.4 years earlier in exposed children than in unexposed children, they added.

In the entire cohort and when the analysis was restricted to term-born children, exposure to corticosteroids was associated with attention deficit-hyperactivity or conduct disorders, emotional disorders, and sleep disorders, among others, although "these findings should be regarded as exploratory because of the possibility of type I error," the authors noted.

In addition to the lack of data on the timing of corticosteroid exposure and dose, and mental disorder diagnoses made in primary care, "residual confounding cannot be ruled out," the authors reported. The study's generalizability is limited due to the Finnish population sampled, they added.

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