Antenatal corticosteroid exposure linked to higher infection risk

The odds of developing infectious diseases are greater in full-term infants exposed to antenatal corticosteroids (ACS) vs those unexposed, according to a recent study published in JAMA Network Open.¹

Pregnancies with significant preterm birth risk are often managed using ACS, which has been linked to improved respiratory outcomes at later gestations.² This has led to a significant increase in ACS use, but concerns have arisen about potential adverse developmental effects.¹

“However, to date, no study has investigated the long-term risk of ACS exposure on infectious diseases in childhood and adolescence through adulthood,” wrote investigators.

Assessing ACS exposure

The study was conducted to evaluate the link between prenatal ACS exposureand infectious disease risks in preterm and full-term infants. Patients were included from the Consortium for the Study of Pregnancy Treatments cohort. Data from Scotland between 1997 and 2018 and from Finland between 2006 and 2018 was included in the analysis.

Patients from Scotland were followed until the age of 21 years and those from Finland until the age of 12 years. Those with major congenital anomalies or missing ACS exposure information were excluded. Exposure was defined as prenatal administration of at least 1 ACS.

An initial respiratory infection diagnosis was reported as the primary outcome, while the secondary outcome was the first diagnosis of a non-respiratory infection. International Statistical Classification of Disease and Related Health Problems, Tenth Revision codes were used to identify respiratory infections.

Categories of respiratory infections included lower respiratory tract infections and upper respiratory tract infections. Covariates included age at birth, parity, maternal smoking, maternal diabetes, gestational age at birth, country, year of birth, mode of birth, birth weight, and sex of child.

Infection incidence and risk

There were 1,548,538 mother-child pairs with a mean maternal age of 29.4 years and mean gestational age at birth of 39.2 weeks included in the analysis. Forty-nine percent of neonates were female, and 57.3% of patients were Scottish while 42.7% were Finnish. ACS exposure was reported in 3.2% of children, preterm birth in 70.7%, and full-term birth in 29.3%.

Offspring were aged a median 494 days at first infectious disease episode vs 567 days at first nonrespiratory infectious disease episode. Incidence rates in ACS-exposed children were 65.2 and 30 per 1000 person-years, respectively, vs 39.8 and 17.9 per 1000 person-years, respectively, in those unexposed, highlighting increased rates from ACS exposure.

A decline in incidence rates was correlated with gestational age at birth. For example, an incidence rate of 82 per 1000 person-years was reported for infectious disease among those born from 28 weeks 0 days to 31 weeks 6 days’ gestation, vs 32 per 1000 person-years for noninfectious diseases.

Long-term implications

In those born from 39 weeks 0 days to 41 weeks 6 days’ gestation, these rates were 38.2 vs 17.3 per 1000 person-years, respectively. Overall, a hazard ratio of 1.19 was reported for respiratory infection among children with ACS exposure vs no exposure.

These results highlighted increased infection risk through the age of 21 years following prenatal ACS exposure. Investigators concluded ACS treatment should be provided judiciously because of the potential long-term effects.

“Mechanistic studies are warranted to identify how ACS affect susceptibility to infections and to allow development of interventions,” wrote investigators.

References

1. Decrue F, Frier EM, Lin C, et al. Antenatal corticosteroids and infectious diseases throughout childhood. JAMA Netw Open. 2025;8(10):e2536809. doi:10.1001/jamanetworkopen.2025.36809
2. Committee on Obstetric Practice. Committee opinion no. 713: antenatal corticosteroid therapy for fetal maturation.Obstet Gynecol. 2017;130(2):e102-e109. doi:10.1097/AOG.0000000000002237