The use of antenatal steroids to accelerate fetal lung development and induce endogenous surfactant production is perhaps one of the most important advances in the field of obstetrics to improve the outcome of the very premature neonate. The recommendation of the 1994 NIH Consensus Conference was that all pregnant women between 24 and 33 completed weeks of gestation who are at risk of preterm delivery within 7 days should be considered candidates for antenatal treatment with a single course of corticosteroids. However the very premature infant accounts for a relatively small portion of preterm birth. Over 9% of all births in 2005 were between 34 and 36 completed weeks with a third of those estimated to have some form of respiratory morbidity. In 2005, at a National Institute of Child Health and Human Development (NICHD) workshop to address this emerging issue, one of the recommendations made to improve outcomes was to investigate the use of antenatal corticosteroids in this "late preterm" population. This study is a collaborative effort of the NICHD MFMU Network, which consists of fourteen academic clinical centers, a data coordinating center, and the Pregnancy and Perinatology Branch of the NICHD. The proposed study design is a randomized, double-masked, clinical trial of 2800 women with a singleton pregnancy who are between 34 weeks 0 days and 36 weeks 5 days with spontaneous preterm labor or ruptured membranes, or whose care providers have scheduled delivery to take place in the next 7 days, and no later than 36 weeks 6 days. Women with prior corticosteroid use during pregnancy, and those whose delivery is expected within 6 hours will be excluded. Gestational age is determined by a standardized algorithm prior to randomization. Eligible and consenting women will be randomized to a course of two intramuscular injections containing 12 mg of betamethasone, 24 hours apart or to a similar course of an identically appearing placebo. The first dose will be administered immediately after randomization. All women will be followed until hospital discharge following delivery and neonates until discharge or 120 days of age, whichever is sooner. The composite primary outcome is stillbirth or neonatal death before 24 hours or the need for neonatal respiratory support within the first 72 hours of life. Respiratory support is defined as the use of continuous positive airway pressure or humidified high-flow nasal cannula for at least two continuous hours, oxygen requirement of FiO2 e 0.3 for at least four continuous hours, or mechanical ventilator use. The use of ECMO is also included in the primary outcome. In summary, antenatal corticosteroids could potentially reduce respiratory morbidity in newborn infants born in the late preterm period, which in turn could translate into a lasting improvement in the health of children, and a reduction in burden on the health care system.
The increase in the rate of preterm birth over the past 10 years has been driven in part by the increase in late preterm births, defined as those births occurring between 34 and 36 weeks. Late preterm infants are more likely to suffer complications such as respiratory distress, hypothermia, and jaundice and are readmitted to the hospital more frequently than infants born at term. The use of antenatal corticosteroids has been shown to improve lung function in very premature infants, but has not been evaluated in those likely to deliver in the late preterm period. If shown to reduce the need for respiratory support and thus to decrease the rate of special care nursery admissions and improve short-term outcomes, the public health and economic impact will be considerable.