This document summarizes a recent study on the use of antenatal corticosteroids for late preterm deliveries between 34-36 weeks gestation. The study found that administering betamethasone to women at risk of late preterm delivery significantly reduced neonatal respiratory complications compared to placebo. While neonatal hypoglycemia was increased in babies exposed to betamethasone, no other adverse neonatal outcomes were observed. Based on these results, major obstetric organizations now approve the use of antenatal corticosteroids in certain late preterm pregnancies to reduce respiratory morbidity in newborns. Further research is still needed to fully understand the efficacy and safety of this treatment approach in late preterm gestations.

1. DR. ALLEN CHERER
Antenatal
Corticosteroid
Use for Late
Preterm
Delivery

2. In 1972, Drs. Liggins and Howie published their
landmark study demonstrating that antenatal
corticosteroids administered to women 24-36
weeks of gestation reduced the incidence of
respiratory distress syndrome and neonatal
mortality. Liggins had previously noted that
lambs, treated with intrafetal ACTH, cortisol, or
dexamethasone, delivered prematurely, and
sacrificed, demonstrated partially expanded
lungs.

3. Such alveolar stability was not typically noted
until later in gestation. It suggested to Liggins
that glucocorticoids might cause premature
liberation of surfactant into the alveoli and
served as the basis for his study. In the trial, the
most significant difference in the incidence of
respiratory distress syndrome among those
treated vs. not treated with corticosteroids
occurred in those gestations less than 32 weeks.

4. Although those gestations treated between 32
and 37 weeks exhibited a decreased incidence
of respiratory distress, the number did not reach
statistical significance. Nevertheless, even at
that time, Liggins postulated that mechanisms
in addition to enhanced surfactant production
and release might be responsible for the
improved pulmonary function noted in more
advanced gestations treated with antenatal
corticosteroids.

5. Interestingly, despite the findings of the initial
study and similar results in multiple subsequent
studies , the 1994 NIH Consensus report on the
effect of corticosteroids for fetal maturation on
perinatal outcomes found that only 20% of
women who delivered newborns 501-1500
grams received the benefit of antenatal
steroids.

6. After a thorough review of available evidence,
including 12 year neurodevelopmental follow up
showing no adverse outcomes, the Consensus
Panel felt the benefits of antenatal
administration of corticosteroids vastly
outweigh the risks and all fetuses between 24
and 34 weeks gestation at risk of preterm
delivery should be considered candidates for
antenatal treatment.

7. Only in those few pregnancies where
corticosteroids would have an adverse effect on
the mother or delivery was imminent should
steroid treatment be withheld. In addition,
although Grade 1 evidence existed at the time to
support the use of antenatal corticosteroids for
gestations greater than 34 weeks, it was judged
insufficient to recommend their use.

8. Since the Consensus statement, the use of
antenatal corticosteroid use has become
common and has resulted in considerable
reduction in mortality and morbidity, as well as
total health care costs. In addition, further
neurodevelopmental follow up, including the
original Auckland steroid trial participants,
continues to demonstrate no adverse effects on
psychological functioning and health-related
quality of life.

9. Other studies have demonstrated a decrease in
overall respiratory disease in infants born
beyond 34 weeks who had previously been
exposed to antenatal corticosteroids when
compared to unexposed infants born at similar
gestations.

10. More than 300,000 pregnancies deliver in the late
preterm period (34 0/7 – 36 6/7 weeks gestation)
each year in the United States. Seventy per cent of
Intensive Care Nursery admissions are late preterm
newborns. Their increasing numbers and the
broad range and severity of respiratory disorders
with which they present beg for a re-evaluation of
antenatal corticosteroid use in this range of
gestations. This is especially appropriate with a
better understanding of the multiple actions of
corticosteroids as gestation approaches term.

11. A recent study, titled Antenatal Late Preterm
Steroids (ALPS), a Randomized Trial to Reduce
Neonatal Respiratory Morbidity, was published in
The New England Journal of Medicine in April,
2016. The study enrolled over 2800 women with
singleton pregnancies at high risk for late preterm
delivery.

12. The participants were randomized to receive
antenatal betamethasone by injection or a
matching placebo. Greater than 80% of women in
the trial delivered prior to 37 weeks gestation. The
primary outcome was a neonatal composite of
treatment in the first 72 hours (CPAP or High Flow
Nasal Cannula for at least 2 hours, supplemental
oxygen with fraction of inspired oxygen of at least
0.3 for at least 4 hours, mechanical ventilation, or
ECMO) or stillbirth or neonatal death within 72
hours of birth.

13. The study found a significant decrease in neonatal
respiratory complications in the group given the
steroid treatment (11.6% vs. 14.4%). In addition,
severe respiratory complications occurred
significantly less frequently in the betamethasone
group. The incidence of neonatal hypoglycemia
was increased in those treated with
betamethasone (24% vs. 14.9%), but no other
adverse neonatal outcomes were noted between
the groups.

14. The study is authoritative due to its size,
generalizability, and methodologic rigor. Although
the issue of long term follow up cannot be
specifically addressed, follow up studies of similar
treatment in earlier gestations are reassuring. Late
preterm births comprise a high risk group for
hypoglycemia regardless of maternal antenatal
steroid treatment and warrant vigilant monitoring
during the newborn period.

15. In sum, the findings of the Antental Late Preterm
Steroids study are consistent with other
randomized controlled trials of antenatal
corticosteroids administered at gestations less
than 34 weeks.

16. Both the American College of Obstetrics and
Gynecology with an endorsement by the American
Academy of Pediatrics and the Society for
Maternal-Fetal Medicine have addressed and
published recommendations based on the study’s
findings. Although the recommendations do not
establish exclusive standards of care, the
organizations approve the use of antenatal
corticosteroids in certain defined late preterm
pregnancies.

17. It is only with thoughtful application of the
recommendations and further studies that the
efficacy and safety of antenatal steroids in the late
preterm pregnancy will be realized. It is a
significant start.