Antenatal Steroids May Improve Respiratory Outcomes for Late Preterm Births

EBM Focus - Volume 11, Issue 6

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Reference - N Engl J Med 2016 Feb 4 early online (level 1 [likely reliable] evidence)

  • Antenatal corticosteroids are recommended for pregnant women at risk of preterm delivery at 24-34 weeks gestation, but little data is available to determine if late preterm delivery between 34 and 37 weeks may also benefit from this intervention.
  • Single course betamethasone significantly decreased the need for respiratory support, severe respiratory complications, resuscitation at birth, surfactant use, transient tachypnea of the newborn, and bronchopulmonary dysplasia compared to placebo, but there were no significant differences in the need for mechanical ventilation or respiratory distress syndrome.
  • Betamethasone was associated with an increased risk of neonatal hypoglycemia, however this increase did not translate into an increased risk of hypoglycemia-related adverse events or a longer hospital stay.

The American College 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 (Obstet Gynecol 2016 Jan;127(1):190). This intervention has been shown to reduce neonatal mortality and Respiratory Distress Syndrome (RDS) of the newborn (Cochrane Database Syst Rev 2006 Jul 19;(3):CD004454,Obstet Gynecol 2015 Jun;125(6):1385). 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 (BMJ 2011 Apr 12;342:d1696, Gynecol Obstet Invest 2010;70(2):95). 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 betamethasone 12 mg vs. placebo intramuscularly with 2 doses administered 24 hours apart.
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 ECMO. 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 = 0.02, NNT 36) and severe respiratory complications (8.1% vs. 12.1%, p < 0.001, NNT 25). Betamethasone was also associated with 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 < 0.001, NNH 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 1-2 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.

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