Antenatal Betamethasone Exposure at the Threshold of Viability: Survival and Neonatal Outcomes at 21–25 Weeks of Gestation

Introduction: Survival and short-term neonatal outcomes in preterm infants remain a significant clinical challenge. Although it is known that antenatal corticosteroids reduce neonatal mortality and morbidity when administered between 24 and 34 weeks of gestation, evidence regarding their use in borderline pregnancies is limited. The aim of this study was to evaluate the effect of antenatal betamethasone exposure on neonatal mortality and morbidity in infants born between 21 and 25 weeks of gestation. Materials and Methods: This retrospective study includes newborns born at Mersin City Training and Research Hospital between 1 January 2021 and 1 January 2026, at gestational ages ranging from 210/7 to 256/7 weeks, who underwent resuscitation in the delivery room and were admitted to the neonatal intensive care unit. Neonatal clinical and maternal characteristics, pregnancy and delivery characteristics, antenatal corticosteroid exposure, the need for respiratory support, neonatal morbidities, and mortality data were evaluated. The primary outcome was survival to discharge or transfer alive; secondary outcomes included recorded neonatal morbidities and their composites with death. Descriptive statistics were presented as medians (25th–75th percentiles), counts, and percentages. Group comparisons used the Kruskal–Wallis or Mann–Whitney U test for continuous variables and Fisher exact or Fisher–Freeman–Halton exact tests for binary categorical variables. Adjusted logistic regression assessed associations with clinical outcomes; sensitivity analyses included restriction to singleton infants. Sibling correlation was not accounted for in the 108-infant analysis. Results: The study included 108 preterm infants born at 21–25 weeks gestation. Thirty of the infants (27.8%) received a full/booster dose of betamethasone, 31 (28.7%) received an incomplete dose, and 47 (43.5%) did not receive betamethasone. Survival rates in the complete, incomplete, and no-betamethasone groups were 66.7%, 41.9%, and 14.9%, respectively (p < 0.001). In the main logistic regression model adjusted for gestational week, sex, and birth weight, compared with the group that did not receive betamethasone, incomplete exposure was associated with a 4.38-fold higher probability of survival, while complete exposure was associated with an 11.95-fold higher probability of survival. Incomplete and complete betamethasone exposure were associated with a lower likelihood of outcomes such as severe intraventricular hemorrhage or death. Complete exposure was also associated with a lower likelihood of the composite outcomes of necrotizing enterocolitis or death and retinopathy of prematurity or death. Conclusions: Antenatal betamethasone exposure in the management of periviable infants may offer potential benefits in terms of neonatal survival and morbidity. However, evaluating survival alone as a measure of a successful neonatal outcome is insufficient; serious neonatal morbidities and long-term neurodevelopmental outcomes must also be considered in the clinical decision-making process. To reduce uncertainty in this area, there is a need for studies with larger sample sizes, involving multiple centers, and including long-term follow-up.