The Impact of Late Preterm Steroids in Reducing Neonatal Respiratory Morbidity in the US

In the US, 280,000 infants are born in the late preterm period (34-36 weeks of gestation) each year, and there are marked disparities in preterm birth rates among racial and ethnic groups. Respiratory morbidity remains a leading cause of complications resulting from prematurity; among late preterm births, 10% of neonates will experience respiratory complications. The Antenatal Late Preterm Steroids Trial, a randomized controlled trial (RCT) of 2,831 individuals at risk for late preterm delivery, demonstrated that antenatal steroids reduced severe neonatal respiratory complications by 34%. However, routine administration of antenatal late preterm steroids (ALPS) remains underutilized in the US due to the controversy surrounding which populations experience the greatest respiratory benefit in relation to the potential risks. The lack of granular efficacy data has divided clinicians about when to offer ALPS, curtailing its full-scale adoption and leading to heterogeneous use across the US. The overall objective of the project is to reduce preventable neonatal respiratory morbidity by generating clinical evidence that is urgently needed to help obstetricians, neonatologists, and policymakers reach a consensus on appropriate ALPS administration in the US. First, to inform quality monitoring efforts, we will identify patient and hospital factors associated with an individual’s likelihood of receiving ALPS and quantify the proportion of hospital-level variation that remains unexplained by these factors (Aim 1). Next, we will leverage hospital-level variation in ALPS use to estimate the effectiveness of ALPS outside the clinical trial setting using a difference-in-differences (DID) design (Aim 2). The study team has considerable experience with this approach, which involves conceptualizing the differential adoption of ALPS as a natural experiment and can be used to estimate unbiased causal effects even in the presence of unmeasured confounders, which biases traditional cohort study designs. Last, we will rely on the technical expertise of the NCI’s cancer modeling consortium to develop and validate a microsimulation model for late preterm birth. This approach will allow us to examine how policies designed to increase ALPS utilization could reduce respiratory morbidity and other neonatal outcomes (e.g., hypoglycemia episodes, NICU admissions) among late preterm births in the US using this comprehensive simulation modeling framework (Aim 3). To complete this work, we will draw on data from the ALPS RCT, US vital statistics, and patient- and hospital-level information from the Premier Healthcare Database (PHD), an existing data set that includes information on the care of nearly 1 million births from >800 hospitals annually (25% of all US births). The multi-disciplinary team’s expertise in clinical obstetrics and neonatology, health services research, quasi-experimental methods, and simulation modeling has uniquely positioned our team to address these critical gaps. Results from this study will have direct, immediate, and actionable implications for the individuals at risk of late preterm delivery and their neonates, their families, clinicians, and policymakers. Project Number: 1R01HL176836-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Mark Clapp (+1 co-PI) | Institution: MASSACHUSETTS GENERAL HOSPITAL, BOSTON, MA | Award Amount: $667,776 | Activity Code: R01 | Study Section: Special Emphasis Panel[ZRG1 HSS-P (90)] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HL17683601