Can Antenatal Corticosteroids Cause Later Childhood Effects?

Babies who were exposed to antenatal corticosteroids are at an increased risk of adverse health outcomes later on, according to new research published in the BMJ.

Antenatal corticosteroids are considered a key intervention for pregnant people who are at risk of preterm delivery earlier than 34 weeks. The drugs reduce the risk for perinatal and neonatal death, and decrease the risk of developing respiratory distress syndrome.

However, how these drugs affect these infants into childhood has been less widely studied, according to the new systematic review and meta-analysis of 1.6 million infants published last week.

About 40% of infants exposed to the steroids before 34 weeks gestation were born at full-term, but were more likely to have a neonatal intensive care admission, be intubated, have a reduced head circumference, and develop long-term neurodevelopmental or behavioral disorders in childhood.

Study authors wrote that clinicians need to more carefully assess the risks and benefits for individual pregnant patients. They also noted the future need for better ways to help predict preterm birth, as well as assessments for clinicians to use when considering prescribing antenatal corticosteroids.

"Steroids are powerful medications,” said Sarah McDonald, MD, professor and maternal-fetal medicine specialist in the Department of Obstetrics & Gynecology at McMaster University, Hamilton, Canada, and lead study author. "With power comes responsibility. As physicians, we want to use steroids to help those who need it (the smallest babies), but avoid using them if birth is unlikely to be very early as there may be developmental harms associated with steroids, particularly if babies are not born very early.”

Study Findings and Potential Future Risks

McDonald and colleagues analyzed data from seven randomized controlled trials and 10 population-based cohort studies that included data on infants with exposure to antenatal corticosteroids born before 34 weeks, between 35 and 36 weeks, and those born at term (≥ 37 weeks)

The researchers found that around 40% of infants who were exposed to antenatal corticosteroids before 24 weeks were born at term, but with associated risk for short- and long-term effects.

These risks, they found, included neonatal intensive care admission (adjusted odds ratio, 1.49; 95% CI, 1.19 - 1.86), intubation (unadjusted relative risk, 2.59), reduced head circumference (adjusted mean difference, −0.21; 95% CI, −0.29 to −0.13), and long-term neurodevelopmental or behavioral disorders (adjusted hazard ratio [AHR], 1.47; 95% CI 1.36 - 1.60).

The researchers found similar results in over half of exposed infants born at term or late preterm.

The findings align with a second study, published online last week in the BMJ, that compared more than 45,000 exposed infants in Taiwan to almost 2 million infants with no exposure. Exposure to one course of antenatal corticosteroids (compared with no exposure) increased the risk for overall serious infections (AHR, 1.32; 95% CI, 1.18 - 1.47, P < .001 ), acute gastroenteritis (AHR, 1.35; 95% CI, 1.10 - 1.65; P < .001), sepsis (AHR, 1.74; 95% CI, 1.16 - 2.61; P = .01), and pneumonia (AHR, 1.39; 95% CI, 1.17 - 1.65; P < .001) in the first 12 months of life.

The findings create a better understanding of potential future risks, according to G. Thomas Ruiz, MD, ob/gyn lead at MemorialCare Orange Coast Medical Center in Fountain Valley, California, who was not affiliated with the research. But he said the findings may not change current clinical practice immediately because of the absence of predictive tools that can inform clinicians of specific risk to a patient.

"Sometimes you have to use steroids, especially for infants at risk of being born very prematurely,” Ruiz said. "There are too many good studies which demonstrate benefits.”

He added that the study also did not demonstrate whether the negative health outcomes directly resulted from the use of corticosteroids alone, or if other factors may play a role.

The study authors report no relevant financial relationships.

BMJ. Published online August 2, 2023. Ninan et al, Yao et al

Lisa M. Basile, MFA, is an award-nominated health writer and author.

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