Caroline Helwick

February 04, 2016

ATLANTA — A National Institutes of Health study has shown that infants born at 34 to 36 weeks of gestation can benefit from antenatal steroids in much the same way that younger preemies do.

In a study of 2831 women, the use of antenatal betamethasone reduced the chance of respiratory complications in "late" preterm infants, who constitute about 8% of all deliveries.

"Our results indicate that prenatal steroid therapy for women delivering late preterm infants could greatly reduce the rate of serious respiratory complications," said Uma Reddy, MD, from the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland.

"Betamethasone is the standard of care for women delivering at 34 weeks and earlier, but we have not had data for those born at 34 to 37 weeks. The conventional thinking is that these babies do so well that it's not necessary, but it turns out that they also have increased risk for respiratory problems and admission to the neonatal intensive care unit," Dr Reddy explained.

"The study was undertaken to determine whether steroids help in this age group," she said.

The study results were presented by Cynthia Gyamfi-Bannerman, MD, from the perinatal clinic at the Columbia University Medical Center in New York City, here at the Society for Maternal-Fetal Medicine 2016 Pregnancy Meeting, and were published online simultaneously in the New England Journal of Medicine.

Women who participated in the study were in weeks 34 to 36 of their pregnancies and were at high risk of delivering before 37 weeks.

 
Prenatal steroid therapy for women delivering late preterm infants could greatly reduce the rate of serious respiratory complications.
 

The investigators defined a high probability of delivery as preterm labor with intact membranes and at least 3 cm dilation or 75% effacement of the cervix; spontaneous rupture of the membranes; or expected preterm delivery for any other indication by induction or cesarean 24 hours to 7 days after planned randomization, as determined by the obstetric provider.

The team randomly assigned 1429 women to betamethasone 12 mg and 1402 to placebo. The women received two injections, 24 hours apart, of the study medication.

The primary outcome was the need for respiratory support at 72 hours of age. This composite end point consisted of one or more of the following: continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) for 2 consecutive hours or more; oxygen requirement with a fraction of inspired oxygen of at least 30% for 4 continuous hours or more; extra corporeal membrane oxygenation; and the need for mechanical ventilation.

A secondary outcome was severe respiratory morbidity, defined as CPAP or HFNC for 12 continuous hours or more, supplemental oxygen of at least 30% for 24 continuous hours or more, extra corporeal membrane oxygenation, or mechanical ventilation.

Other neonatal secondary outcomes included respiratory distress syndrome, transient tachypnea of the newborn, bronchopulmonary, surfactant administration, hyperbilirubinemia, hypoglycemia, necrotizing enterocolitis, intraventricular hemorrhage of grade 3 or 4, neonatal sepsis, and death before discharge.

Maternal secondary outcomes included chorioamnionitis, endometritis, delivery prior to completion of steroids, and length of hospital stay.

Of the 2831 study participants, 1686 (60%) received both doses of the study medication, 1139 (95%) received only one dose and delivered before the second dose could be administered, and six did not receive any of the doses.

Two patients in each group, were lost to follow-up, so the final analysis involved 1427 women in the betamethasone group and 1400 in the placebo group.

There were fewer adverse effects in the betamethasone group than in the placebo group (14.1% vs 20.3%; P < .001), and 95% of these events were local reactions at the injection site.

Neonatal Outcomes Improved With Steroids

Respiratory support at 72 hours, the primary outcome, was less frequent in the betamethasone group than the placebo group (11.6% vs 14.4%; P = .023). The number needed to treat to prevent one event was 35.

The rate of severe respiratory morbidity was lower in the betamethasone group than in the placebo group (8.1% vs 12.1%; P < .001). For this outcome, the number needed to treat was 25.

"Only 25 women have to be treated to prevent one infant from needing either oxygen for 24 hours or mechanical ventilation, CPAP, or HFNC for 12 hours," the investigators report.

Table. Major Outcomes

Outcome Betamethasone Group, % (n = 1427) Placebo Group, % (n = 1400) Relative Risk P Value
Primary outcome 11.6 14.4 0.80 .023
Severe respiratory morbidity 8.1 12.1 0.67 <.001
Respiratory distress syndrome 5.5 6.4 0.87 .356
Transient tachypnea of the newborn 6.7 9.9 0.67 .002
Bronchopulmonary dysplasia 0.6 0.1 0.22 .040
Surfactant use 1.8 3.1 0.59 .031
Chorioamnionitis 1.4 2.3 0.61 .080
Neonatal hypoglycemia 24.0 15.0 1.60 <.001
Proven neonatal sepsis 0.6 0.8 0.80 .623
Necrotizing enterocolitis 0.0 0.1
Time from first dose to delivery, hours 33.0 30.6 .565
Time to first feed, hours 10.0 5.5 .004
Gestational age at delivery, weeks 36.1 36.1 .517

 

Two infants in the betamethasone group died before 72 hours, but not from respiratory causes. Neonatal sepsis, necrotizing enterocolitis, intraventricular hemorrhage, and other complications were rare and were no more common in the betamethasone group than in the placebo group.

Infants in the betamethasone group were less likely than those in the placebo group to spend 3 days or more in the intensive or intermediate-care nursery. There were no differences in birth weights between the two groups, or in the rate of infants who were small for gestational age. In terms of maternal outcomes, there were no differences in the incidence of chorioamnionitis, the incidence of endometritis, time to delivery, or length of hospital stay.

"We saw a lot of benefits from the use of steroids and no differences in many other things we are concerned about," Dr Reddy reported.

Because 8% of all babies are late preterm, the use of steroids would have "a huge impact," she added.

Dr Reddy also pointed out that late preterm infants are already at risk for neonatal hypoglycemia, and the condition was self-limited. "We recommend that they be monitored for low blood sugar," she said.

Findings Are "Generalizable"

These findings are from a randomized controlled trial, the "gold standard" in study design, said Judette Louis, MD, from the Department of Obstetrics and Gynecology at Morsani College of Medicine and the College of Public Health at the University of South Florida in Tampa.

The strengths of the study include the large number of patients and the diversity of study sites, she told Medscape Medical News. "This makes their findings generalizable to the overall obstetric population," Dr Louis explained.

She pointed out that a number of studies have attempted to determine whether antenatal steroids are beneficial in the late preterm birth period. Two small studies showed no benefit, but they were insufficiently powered because of the size of the study population; however, a subsequent larger observational study did show improved outcomes in women who received antenatal corticosteroids, she said.

"Their findings of a benefit are similar to the current study. However, the current study has a superior study design," she said. "The results of this trial provide further support for the use of antenatal corticosteroids in women at 34 weeks of gestation and beyond."

"We now have enough information to recommend that providers administer antenatal corticosteroids in clinical practice to women in the thirty-fourth to thirty-sixth week of pregnancy who are at high risk for delivering before 37 weeks because of the significant neonatal benefits," Dr Louis concluded.

This study was cofunded by National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute. Dr Reddy and Dr Louis have disclosed no relevant financial relationships.

Society for Maternal-Fetal Medicine (SMFM) 2016 Pregnancy Meeting: Abstract 1. Presented February 4, 2016.

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