ATLANTA – Administration of betamethasone to mothers at risk of late preterm birth reduced the risk of perinatal respiratory complications – including supplemental oxygen, ventilation, and death – by 20%.
The steroid was also associated with a 33% reduction in the risk of severe respiratory complications, Dr. Cynthia Gyamfi-Bannerman reported at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine. The study was simultaneously published in the New England Journal of Medicine (2016; doi: 10.1056/NEJMoa1516783.).
“This finding is practice changing and it’s ready for prime time,” Dr. Gyamfi-Bannerman said in an interview. “Right now there are 300,000 late preterm deliveries every year in this country, and if we can do something now to improve their outcomes without imparting any harm, then I think we should do that right away.”
Although standard practice for early preterm infants, betamethasone use in the late preterm period has not been well studied since the 1970s, said Dr. Gyamfi-Bannerman of Columbia University, New York. At that time, it was determined to be unhelpful; since then, studies have focused on its use in earlier time points. However, she said, those early studies were small and had methodologic problems.
Dr. Gyamfi-Bannerman’s study is the first large, placebo-controlled trial to examine the steroid’s use in the late preterm period. It was conducted in 17 centers and comprised 2,831 women with a singleton pregnancy of 34 to 36 weeks, 5 days’ gestation. All women were at high risk of delivery during the late preterm period, which was considered up to 36 weeks, 6 days.
Women were assigned to receive two injections of either 12 mg betamethasone or placebo 24 hours apart. The primary neonatal outcome was a composite of treatments required during the first 72 postnatal hours, including positive airway pressure or high-flow nasal cannula for at least 2 hours; supplemental oxygen for at least 4 hours; extracorporeal membrane oxygenation or mechanical ventilation; or stillbirth or neonatal death within that 72-hour period.
The women were a mean of 28 years old. Labor with intact membranes was the most common risk factor for preterm delivery; followed by ruptured membranes, and gestational diabetes or preeclampsia. Other risks included expected delivery for intrauterine growth restriction or oligohydramnios.
Outcomes data were available for 2,827 infants. There were no stillbirths or deaths within the first 72 hours.
The primary outcome was significantly less common among those who received betamethasone (11.6% vs. 14.4%; relative risk, 0.80). The number needed to treat to prevent one outcome was 35.
A secondary analysis eliminated 32 infants with a major congenital anomaly that had been unrecognized before birth; the significant benefit of betamethasone was unchanged.
The rate of the composite outcome of severe respiratory complications was also significantly lower in the betamethasone group (8.1% vs. 12.1%; RR, 0.67). The number needed to treat to prevent one case of a severe respiratory complication was 25.
While rates of respiratory distress syndrome, apnea, and pneumonia were similar in the two groups, other disorders were significantly less common in the treated group, including transient tachypnea of the newborn (6.7% vs. 9.9%); bronchopulmonary dysplasia (0.1% vs. 0.6%), and the composite of the respiratory distress syndrome, transient tachypnea of the newborn, or apnea (13.9% vs. 17.8%).
Significantly fewer infants in the treatment group required resuscitation at birth (14.5% vs. 18.7%) and surfactant (1.8% vs. 3.1%).
The use of betamethasone was not associated with any clinically significant adverse neonatal effects with one exception, Dr. Gyamfi-Bannerman said. Neonatal hypoglycemia occurred in 24%, compared with 15% of those in the placebo group – a significant 60% increased relative risk. There were no hypoglycemia-related adverse events; nor did the condition affect length of stay. In fact, infants with hypoglycemia were discharged an average of 2 days earlier than were those without “suggesting that the condition was self-limiting.” It was probably associated with earlier feeding in these babies, she added.
Late preterm birth is one of the largest risk factors for neonatal hypoglycemia, she noted.
“To put this in perspective, our numbers were similar or even less than those reported in the literature,” she said. “Our nurses are familiar with this risk and these babies are being checked regularly. We should be looking for it, in the way that we normally would.”
The study was supported by grants from the National Institutes of Health. Dr. Gyamfi-Bannerman reported having no financial disclosures.
Watch Dr. Gyamfi-Bannerman discuss the study here.