Antenatal Corticosteroid Use for Late Preterm Delivery

DR. ALLEN CHERER

AntenatalCorticosteroidUse for LatePretermDelivery

In 1972, Drs. Liggins and Howie published theirlandmark study demonstrating that antenatalcorticosteroids administered to women 24-36weeks of gestation reduced the incidence ofrespiratory distress syndrome and neonatalmortality. Liggins had previously noted thatlambs, treated with intrafetal ACTH, cortisol, ordexamethasone, delivered prematurely, andsacrificed, demonstrated partially expandedlungs.

Such alveolar stability was not typically noteduntil later in gestation. It suggested to Ligginsthat glucocorticoids might cause prematureliberation of surfactant into the alveoli andserved as the basis for his study. In the trial, themost significant difference in the incidence ofrespiratory distress syndrome among thosetreated vs. not treated with corticosteroidsoccurred in those gestations less than 32 weeks.

Although those gestations treated between 32and 37 weeks exhibited a decreased incidenceof respiratory distress, the number did not reachstatistical significance. Nevertheless, even atthat time, Liggins postulated that mechanismsin addition to enhanced surfactant productionand release might be responsible for theimproved pulmonary function noted in moreadvanced gestations treated with antenatalcorticosteroids.

Interestingly, despite the findings of the initialstudy and similar results in multiple subsequentstudies , the 1994 NIH Consensus report on theeffect of corticosteroids for fetal maturation onperinatal outcomes found that only 20% ofwomen who delivered newborns 501-1500grams received the benefit of antenatalsteroids.

After a thorough review of available evidence,

including 12 year neurodevelopmental follow upshowing no adverse outcomes, the ConsensusPanel felt the benefits of antenataladministration of corticosteroids vastlyoutweigh the risks and all fetuses between 24and 34 weeks gestation at risk of pretermdelivery should be considered candidates forantenatal treatment.

Only in those few pregnancies wherecorticosteroids would have an adverse effect onthe mother or delivery was imminent shouldsteroid treatment be withheld. In addition,

although Grade 1 evidence existed at the time tosupport the use of antenatal corticosteroids forgestations greater than 34 weeks, it was judgedinsufficient to recommend their use.

Since the Consensus statement, the use ofantenatal corticosteroid use has becomecommon and has resulted in considerablereduction in mortality and morbidity, as well astotal health care costs. In addition, furtherneurodevelopmental follow up, including theoriginal Auckland steroid trial participants,continues to demonstrate no adverse effects onpsychological functioning and health-relatedquality of life.

Other studies have demonstrated a decrease inoverall respiratory disease in infants bornbeyond 34 weeks who had previously beenexposed to antenatal corticosteroids whencompared to unexposed infants born at similargestations.

More than 300,000 pregnancies deliver in the latepreterm period (34 0/7 – 36 6/7 weeks gestation)

each year in the United States. Seventy per cent ofIntensive Care Nursery admissions are late pretermnewborns. Their increasing numbers and thebroad range and severity of respiratory disorderswith which they present beg for a re-evaluation ofantenatal corticosteroid use in this range ofgestations. This is especially appropriate with abetter understanding of the multiple actions ofcorticosteroids as gestation approaches term.

A recent study, titled Antenatal Late PretermSteroids (ALPS), a Randomized Trial to ReduceNeonatal Respiratory Morbidity, was published inThe New England Journal of Medicine in April,2016. The study enrolled over 2800 women withsingleton pregnancies at high risk for late pretermdelivery.

The participants were randomized to receiveantenatal betamethasone by injection or amatching placebo. Greater than 80% of women inthe trial delivered prior to 37 weeks gestation. Theprimary outcome was a neonatal composite oftreatment in the first 72 hours (CPAP or High FlowNasal Cannula for at least 2 hours, supplementaloxygen with fraction of inspired oxygen of at least0.3 for at least 4 hours, mechanical ventilation, orECMO) or stillbirth or neonatal death within 72hours of birth.

The study found a significant decrease in neonatalrespiratory complications in the group given thesteroid treatment (11.6% vs. 14.4%). In addition,

severe respiratory complications occurredsignificantly less frequently in the betamethasonegroup. The incidence of neonatal hypoglycemia was increased in those treated withbetamethasone (24% vs. 14.9%), but no otheradverse neonatal outcomes were noted betweenthe groups.

The study is authoritative due to its size,

generalizability, and methodologic rigor. Althoughthe issue of long term follow up cannot bespecifically addressed, follow up studies of similartreatment in earlier gestations are reassuring. Latepreterm births comprise a high risk group forhypoglycemia regardless of maternal antenatalsteroid treatment and warrant vigilant monitoringduring the newborn period.

In sum, the findings of the Antental Late PretermSteroids study are consistent with otherrandomized controlled trials of antenatalcorticosteroids administered at gestations lessthan 34 weeks.

Both the American College of Obstetrics andGynecology with an endorsement by the AmericanAcademy of Pediatrics and the Society forMaternal-Fetal Medicine have addressed andpublished recommendations based on the study’sfindings. Although the recommendations do notestablish exclusive standards of care, theorganizations approve the use of antenatalcorticosteroids in certain defined late pretermpregnancies.

It is only with thoughtful application of therecommendations and further studies that theefficacy and safety of antenatal steroids in the latepreterm pregnancy will be realized. It is asignificant start.