Maternal antenatal corticosteroid exposure linked to mental, behavioral disorders among offspring

Katri Räikkönen

Maternal antenatal corticosteroid treatment exposure appeared significantly associated with pediatric mental and behavioral disorders, according to results of a population-based cohort study published in JAMA.

“Maternal corticosteroid treatment is effective and can be life-saving for babies who are born extremely or very preterm,” Katri Räikkönen, PhD, of the department of psychology and logopedics at University of Helsinki, told Healio Psychiatry. “Although the short-term benefits of this treatment for infant morbidity and mortality are known, the long-term outcomes of treatment exposure have remained uncertain. Long-term neurodevelopmental outcomes after treatment exposure have been of particular concern, since corticosteroids not only cross the placenta, but also the blood-brain barrier and thus may harm fetal brain development.”

Few studies have been conducted on neurodevelopmental outcomes of treatment-exposed term-born children. Further, the researchers noted that to their knowledge, no population-based studies have evaluated associations between treatment exposure and child neurodevelopment, and no studies have tested whether unmeasured familial confounding explained any associations.

Räikkönen and colleagues sought to determine if antenatal corticosteroid treatment was associated with mental and behavioral disorders among children born at term and preterm, as well as to determine the role of familial confounding in these associations. They analyzed nationwide registry data of 670,097 singleton children born in Finland between 2006 and 2017 who survived until 1 year, and they conducted a within-sibpair comparison among term siblings. They used maternal antenatal corticosteroid treatment as the exposure, and any childhood mental and behavioral disorder diagnosed in public specialized medical care settings served as the primary outcome.

Median length of follow up was 5.8 years.

Results showed that among 14,868 (2.22%) children exposed to corticosteroid treatment, 6,730 (45.27%) were born at term and 8,138 (54.74%) were born preterm. Of the 655,229 (97.78%) nonexposed children, 634,757 (96.88%) were born at term and 20,472 (3.12%) were born preterm. A total of 4,128 (1.71%) eligible term-born maternal sibpairs nested within this population were discordant for treatment exposure.

Compared with nonexposure, the researchers reported that treatment exposure was linked to a significantly higher risk for any mental and behavioral disorder among the entire of cohort (12.01% vs. 6.45%; absolute difference = 5.56%; 95% CI, 5.04-6.19; adjusted HR [aHR] = 1.33; 95% CI, 1.26-1.41), term-born children (8.89% vs. 6.31%; absolute difference = 2.58%; 95% CI, 1.92-3.29; aHR = 1.47; 95% CI, 1.36-1.69) and when sibpairs discordant for treatment exposure were compared with those concordant for nonexposure (6.56% vs. 4.17% for within-sibpair differences; absolute difference = 2.4%; 95% CI, 1.67-3.21; aHR = 1.38; 95% CI, 1.21-1.58). Treatment-exposed preterm-born children exhibited a significantly higher cumulative incidence rate of any mental and behavioral disorder compared with nonexposed children; however, the aHR was not significant (14.59% vs. 10.71%; absolute difference = 3.38%; 95% CI, 2.95-4.87; aHR = 1; 95% CI, 0.92-1.09).

“It is important to weigh the balance between the long-term benefits and harms of this treatment, particularly when considering whether to expand its indications to later gestational weeks, which has been debated,” Räikkönen told Healio Psychiatry. “The prognosis of babies who are born preterm at later gestational weeks is very good in high-income countries.”

In a related editorial, Sara B. DeMauro, MD, MSCE, of Roberts Center for Pediatric Research at Children’s Hospital of Philadelphia, noted that these findings call into question current antenatal corticosteroid guidelines.

“The study by Räikkönen [and colleagues] provides new insight into potential adverse effects of antenatal corticosteroid exposure, particularly in infants who are ultimately born full term,” DeMauro wrote. “Although benefits of this therapy outweigh risks in the most vulnerable infants, this may not be true for all infants. 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.” – by Joe Gramigna

Disclosures: The study authors and DeMauro report no relevant financial disclosures.