Level 1 [likely reliable] evidence
The American Congress of Obstetricians and Gynecologists (ACOG) recommends a single course of antenatal corticosteroid in pregnant women between 24 and 34 weeks gestation who are at risk of preterm delivery within 7 days.1 This intervention has been shown to reduce neonatal mortality and respiratory distress syndrome (RDS) of the newborn. 2,3 While late preterm birth is also associated with increased morbidity and mortality compared to term birth, the fetal lungs have already matured in most cases. The data on antenatal corticosteroid use in pregnant women at 34 to 37 week gestation at high risk of preterm delivery is limited and inconsistent. To further investigate the effects of antenatal corticosteroids on late preterm neonates, 2,831 women with singleton pregnancy between 34 and 36 5/7 weeks gestation at high risk of late preterm delivery were randomized to receive 12 mg of betamethasone or placebo intramuscularly, with 2 doses administered 24 hours apart. 4
Only 59.6% of the women (1,686) received both doses of trial medication, as 38.3% (1,083 women) delivered within 24 hours of the first dose. The primary outcome was a composite of the need for respiratory support, stillbirth, or neonatal death within 72 hours of delivery. Respiratory support ranged from high-flow supplemental oxygen to mechanical ventilation and extracorporeal membrane oxygenation. Severe respiratory complications, which included longer periods of respiratory support, were also evaluated. There were no stillbirths or neonatal deaths within 72 hours. Compared to placebo, betamethasone significantly reduced the rates of the primary outcome (11.6% vs 14.4%; P =.02; number needed to treat [NNT], 36) and severe respiratory complications (8.1% vs 12.1%; P <.001; NNT, 25). Betamethasone was also associated with a significantly reduced need for resuscitation at birth, surfactant use, transient tachypnea of the newborn, and bronchopulmonary dysplasia. There were no significant differences in mechanical ventilation, RDS, apnea, pneumonia, neonatal sepsis, or maternal outcomes. However, hypoglycemia was significantly increased in the betamethasone group, compared to placebo (24% vs 15%; P <.001; NNT, 12).
The current trial is the largest and most extensive trial to evaluate antenatal corticosteroids in pregnant women at high risk of late preterm birth to date. The need for respiratory support as well as severe respiratory complications, transient tachypnea of the newborn, and bronchopulmonary dysplasia were all significantly reduced with 1 to 2 doses of betamethasone before birth. The improvement in the primary respiratory outcome is due to differences in need for high-flow nasal cannula and continuous positive airway pressure rather than differences in more invasive interventions such as mechanical ventilation. However, even a few hours of supplemental oxygen can interfere with the initial maternal-infant bonding, and the significance of this was not assessed in this trial. While the rate of hypoglycemia was significantly increased in the betamethasone group, no adverse events related to hypoglycemia were reported, and there was no increase in the length of hospitalization in neonates with hypoglycemia. Overall, the decreased rate of respiratory complications with betamethasone suggests this intervention may improve the respiratory status in late preterm infants, even if there is no difference in rates of RDS. Long-term follow-up will show whether this treatment will have an effect on chronic lung conditions.
Alan Ehrlich, MD, is a deputy editor for DynaMed, Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester.
DynaMed is a database that provides evidence-based information on more than 3,000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals.
- Practice bulletin no. 159 summary: management of preterm labor. Obstet Gynecol. 2016;127:190-191.
- Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. 2006;:CD004454;
- Sotiriadis A, Tsiami A, Papatheodorou S, Baschat AA, Sarafidis K, Makrydimas G. Neurodevelopmental outcome after a single course of antenatal steroids in children born preterm: a systematic review and meta-analysis. Obstet Gynecol. 2015;125:1385-1396.
- Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al. Antenatal betamethasone for women at risk for late preterm delivery. N Engl J Med. 2016;374:1311-1320.