Children exposed to antenatal betamethasone during the late preterm period had similar rates of childhood respiratory impairment at age 6 years or older compared with children exposed to placebo, according to a follow-up study published in Obstetrics & Gynecology.

Researchers conducted a prospective follow-up study of pediatric patients whose parents participated in the Antenatal Late Preterm Steroids (ALPS) trial, a multicenter, double-blind randomized controlled trial evaluating betamethasone in pregnant patients at risk for delivery from 34 0/7 to 36 6/7 weeks’ gestation. The follow-up study included 1,218 pediatric patients aged 6 years or older, including 614 exposed to betamethasone and 604 exposed to placebo. Researchers also enrolled 436 term-born pediatric patients from the STAN trial as a reference cohort, of whom 432 completed spirometry and primary outcome assessment.

The primary outcome was a composite measure of childhood respiratory impairment that included abnormal spirometry findings, physician-diagnosed asthma with daily asthma medication use, or daily asthma medication use during the prior year. Respiratory outcomes were assessed with spirometry testing, caregiver questionnaires, and medication and hospitalization history.

The primary outcome occurred in 35% of pediatric patients exposed to betamethasone and 36% of pediatric patients exposed to placebo, with no statistically significant difference between groups. Rates of abnormal spirometry, asthma diagnosis, and asthma medication use were also similar between groups. Spirometry testing was successfully completed in 98% of ALPS participants enrolled in the follow-up study.

Although the study enrolled fewer participants than originally planned, the observed primary outcome rate was substantially higher than anticipated, giving the final cohort more than 90% power to detect a 30% relative increase or decrease in the primary outcome.

An exploratory secondary analysis showed that ever having wheezing or whistling in the chest was reported in 41% of pediatric patients exposed to betamethasone compared with 46% of pediatric patients exposed to placebo. However, rates of wheezing during the prior year, pneumonia, dry cough at night, and wheezing during or following exercise were otherwise similar between the betamethasone and placebo groups. The researchers noted that secondary analyses were not adjusted for multiple comparisons.

Compared with the term-born reference cohort, pediatric patients from the ALPS cohort had higher rates of some respiratory symptoms regardless of treatment assignment, suggesting that late preterm birth itself may contribute to persistent pulmonary differences. Wheezing during or following exercise occurred in 7% of pediatric patients exposed to betamethasone and 9% of pediatric patients exposed to placebo compared with 4% of pediatric patients in the term cohort. In addition, forced expiratory volume in 1 second/forced vital capacity ratios below the lower limit of normal occurred in approximately 24% of both ALPS groups compared with 18% of term-born pediatric patients.

Prespecified subgroup analyses evaluating private insurance status, cesarean delivery, and sex found no statistically significant interaction with treatment assignment for the primary outcome. Sensitivity analyses accounting for loss to follow-up, secondhand smoke exposure, and postbronchodilator spirometry measurements did not materially alter the findings.

The researchers noted several limitations, including enrollment of 1,218 participants rather than the planned 2,000 because of recruitment challenges and disruptions related to the COVID-19 pandemic. The pandemic also led investigators to discontinue routine postbronchodilator testing because of concerns regarding shared inhaler use. Participants who completed follow-up differed from nonparticipants in smoking exposure, insurance status, and educational attainment, raising the possibility of selection bias.

Researchers additionally observed poor agreement between caregiver-reported household smoking exposure and urine cotinine testing. Nearly 60% of pediatric patients with cotinine evidence of secondhand smoke exposure had caregivers who did not report smoking in the household.

The findings do not alter current recommendations supporting antenatal betamethasone use for pregnant patients at risk for late preterm delivery because of its established short-term neonatal respiratory benefits. However, the study did not demonstrate evidence that late preterm corticosteroid exposure improves long-term pulmonary outcomes during childhood.

“In conclusion, administration of late preterm antenatal corticosteroids improved short-term respiratory outcomes but did not affect childhood pulmonary outcomes, aside from ever having less wheezing or whistling in the chest, compared with those exposed to placebo,” wrote lead study author Cynthia Gyamfi-Bannerman, MD, of the University of California, San Diego, and colleagues.

Disclosures: The study was supported by the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The researchers reported no potential conflicts of interest. Torri D. Metz, MD, Deputy Editor of Obstetrics for Obstetrics & Gynecology, was not involved in the review or decision to publish the study.

Source: Obstetrics & Gynecology