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The impact of exposure to corticosteroids in utero on risk of long-term neurological impairment varied by birth timing, according to a systematic review and meta-analysis.

Children with extremely preterm birth who were exposed to a single course of antenatal corticosteroids had a significantly reduced risk of developing long-term adverse neurodevelopmental outcomes (adjusted OR 0.69, 95% CI 0.57-0.84), reported Kiran Ninan, BHSc, of McMaster University in Ontario, and colleagues.

But for children with late preterm birth, exposure to antenatal corticosteroids was associated with modestly increased risk of investigation for neurocognitive disorders (adjusted HR 1.12, 95% CI 1.05-1.20), the researchers wrote in .

Babies born at full term who were exposed to corticosteroids in utero had a significantly increased risk of developing mental or behavioral disorders (aHR 1.47, 95% CI 1.36-1.60) and proven or suspected neurocognitive disorders (aHR 1.16, 95% CI 1.10-1.21).

"Given that approximately 50% of children who had preterm exposure to antenatal corticosteroids exceeded expectations and were born full term, the timing and dose of antenatal corticosteroid administration should be carefully considered," Ninan and colleagues wrote.

In an , Andrea Duncan, MD, MSCR, of the Children's Hospital of Philadelphia, and colleagues, said that this review shifts the discussion of antenatal corticosteroid administration from "the timing of receipt to the timing of delivery."

It is possible that exposure to antenatal corticosteroids during a term pregnancy may potentially predispose kids to worse neurodevelopment in childhood, the editorialists stated. Moving forward, it will be important to ascertain whether the timing of birth is still significant when considering the possibility that children may have been exposed to multiple courses of antenatal corticosteroids.

"As obstetrical and neonatal-perinatal care continue to evolve and improve, findings such as those presented by Ninan et al should generate new hypotheses and hope," Duncan and colleagues wrote. "Such reports confirm that the developing child is not simply a small adult and should not be treated as such."

The administration of antenatal corticosteroids among women at risk for preterm birth is standard practice, and considered one of the most significant antenatal therapies to improve neonatal outcomes, the editorialists wrote. However, some animal studies have found that there are harmful neurological outcomes associated with steroid use.

In this review, Ninan and colleagues analyzed articles that assessed long-term neurodevelopmental, psychological, and other outcomes among kids who were exposed to corticosteroids in utero. All studies included were published between January 2000 and October 2021 and assessed participant outcomes at 1 year of age or older.

Ninan's group compared outcomes among babies with and without antenatal corticosteroid exposure. They included studies that explored the impacts of exposure to a single course of antenatal corticosteroids (either 24 mg of betamethasone or dexamethasone), as well as multiple courses.

Overall, 30 studies met the inclusion criteria with a total of more than 1.25 million children who were at least 1 year old when the outcomes were assessed. The duration of participant follow-up ranged from 1 to 10 years. Ten of the studies measured long-term outcomes associated with exposure to a single course of antenatal corticosteroids, and 20 studies did not specify the number of courses administered.

Compared to nonexposure, a single course of antenatal corticosteroids was not associated with significant reductions in odds of visual impairment (aOR 1.42, 95% CI 0.57-3.54), auditory impairment (aOR 0.58, 95% CI,0.33-1.01), or moderate or severe cerebral palsy (aOR 0.82, 95% CI 0.56-1.19). However, among infants born extremely preterm, exposure to a single course was associated with a significantly decreased risk of neurodevelopmental impairment, cerebral palsy, and other outcomes.

Having received an unspecified number of courses of antenatal corticosteroids was associated with several neurodevelopmental and psychological outcomes among children with preterm and full-term birth, the authors found.

Ninan and colleagues acknowledged that this review was limited by the scarcity of randomized follow-up data, as well as the inclusion of observational data that could introduce bias. Additionally, the researchers noted that there was a paucity of data describing race and ethnicity, which they stated should be an area for future study.

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