Clinicians should use caution in prescribing corticosteroids to some pregnant patients, according to a new study.

Full-term infants exposed to antenatal corticosteroids (ACSs) had significantly more infections in childhood and adolescence than those who were not exposed, based on data from more than 1.5 million mother-child pairs.

“Our findings suggest that antenatal corticosteroid treatment should be used judiciously, given the potential long-term effects in otherwise healthy term and preterm born children,” said Fabienne Decrue, PhD, researcher at The University of Edinburgh in Edinburgh, Scotland, who led the study.

By contrast, infants born between 28 and 33 weeks’ gestation showed no significant association between exposure to steroids in utero and the risk for infection into childhood and adolescence.

“Our results are reassuring about the potential safety of antenatal corticosteroid treatment in children born before 34 weeks’ gestation,” Decrue said. “In these populations, the clear short-term benefits of treatment outweigh other short- to mid-term risks.”

ACSs are often prescribed to pregnant women between 24 and 33 weeks’ gestation if their risk for preterm delivery is imminent, as advised by the American College of Obstetricians & Gynecologists.

An increasing number of children are exposed to steroids during gestation, according to data from a 2022 study.

But previous studies have linked the use of corticosteroids during pregnancy to a range of adverse outcomes, including admission to the NICU, reduced head circumference, neurodevelopmental disorders, acute gastroenteritis, and pneumonia.
 

However, the association between ACSs and long-term risk for infectious diseases in children has not been well-studied, Decrue said.

In the new study published in JAMA Network Open, Decrue and her colleagues analyzed inpatient and outpatient data from nationwide registries in Scotland and Finland. The study population included more than 1.5 million mothers with singleton children born between 1997 and 2018 in Scotland or between 2006 and 2018 in Finland.

Children were considered exposed if their mothers received at least one dose of a corticosteroid during pregnancy. Their outcomes were tracked until the date of first infection, death, up to age 21 years, or 2018.

Over the course of the long-term follow-up period, 34.4% of children exposed to steroids developed respiratory infections compared to 26.5% of nonexposed children.

Other types of infections were also tracked, including viral, bacterial, gastrointestinal, and soft tissue, of which viral was the most common. Other infections occurred more frequently in ACS-exposed children than in nonexposed children (18.6% vs 13.35%). Viral infections occurred in 11.6% and 7.5% of the exposed and nonexposed children, respectively.

But outcomes depended on when corticosteroids were administered by gestational age group.

Infants born between 28 and 33 weeks exposed to corticosteroids showed no statistically significant associations with infections later on in fully adjusted models.

Exposed infants who were born between 34 and 36 weeks’ gestation had a higher risk for respiratory and other infections with adjusted hazard ratios (aHRs) of 1.10 (95% CI,1.06-1.14) and 1.17 (95% CI,1.11-1.23), respectively, than did infants who had not been exposed to the drugs.

Risks for respiratory and other infections also were greater for exposed children born between 37 and 38 weeks’ gestation (aHRs 1.19 and 1.23, respectively), as well as for those born full-term (aHRs 1.27 and 1.31, respectively), the researchers reported.

The data may help inform discussions of the merits and long-term risks of maternal ACS treatment, Decrue said.

Informing Clinical Decisions

The findings parallel conclusions from studies with shorter follow-up periods, such as a 2023 study, said Aleksandr M. Fuks, MD, professor and chair in the Department of Obstetrics and Gynecology at East Tennessee State University in Johnson City, Tennessee, who was not involved in the research.

“As there was no difference in long-term morbidity from infections among very preterm and moderately preterm infants exposed and not exposed to ACS, the results support continuation of ACS administration to these patients, who are at highest risk of morbidity related to prematurity,” Fuks said.

He said was surprised by missing data for covariates including maternal hypertension and preeclampsia. The study also did not include information on maternal or neonatal vaccinations, which could relate to later infection in children.

The study authors reported receiving support from the Wellcome Trust Clinical Career Development Fellowship. Decrue reported receiving grants from the Swiss National Science Foundation and Bangerter-Rhyner Foundation. Fuks reported having no relevant financial conflicts.