Late preterm antenatal corticosteroids in singleton and twin gestations: a retrospective cohort study

Abstract

Background In 2016, the American College of Obstetricians and Gynecologists recommended antenatal corticosteroids in the late preterm period for women at risk for preterm delivery. Limited real-world evidence exists on neonatal outcomes, particularly for twin gestations, following the guideline change. The study objective is to determine the association of antenatal corticosteroids in late preterm singleton and twin pregnancies with respiratory complications and hypoglycemia in a real-world clinical setting. Methods This is a retrospective cohort study comprising late preterm deliveries (4,341 mother–child pairs) within the Mount Sinai Health System, 2012–2018. The exposure of interest is antenatal corticosteroid administration of betamethasone during pregnancy between 34 0/7 and 36 6/7 weeks. Our primary outcomes are neonatal respiratory complications and hypoglycemia. Multivariable logistic regression was used to estimate the association between antenatal corticosteroid exposure and these two outcomes. We stratified the study population by singleton gestations and twins to minimize the potential confounding from different obstetric management between the two groups. Results Among a total of 4,341 mother–child pairs (3,309 singleton and 1,032 twin mother–child pairs), 745 mothers received betamethasone, of which 40.94% (305/745) received the full course. Relative to no treatment, a full course of betamethasone was associated with reduced odds of respiratory complications (OR = 0.53, 95% CI:[0.31–0.85], p < 0.01) and increased odds of hypoglycemia (OR = 1.86, 95%CI:[1.34–2.56], p < 0.01) in singletons; however, the association with respiratory complications was not significant in twins (OR = 0.42, 95% CI:[0.11–1.23], p = 0.16), but was associated with increased odds of hypoglycemia (OR = 2.18, 95% CI:[1.12–4.10], p = 0.02). A partial course of betamethasone (relative to no treatment) was not significantly associated with any of the outcomes, other than respiratory complications in twins (OR = 0.34, 95% CI:[0.12–0.82], p = 0.02). Conclusions Exposure to antenatal corticosteroids in singletons and twins is associated with increased odds of hypoglycemia. Among singletons, exposure to the full dosage (i.e. two doses) was associated with decreased odds of respiratory complications but this was only the case for partial dose among twins. Twin gestations were not studied by the Antenatal Late Preterm Steroids trial. Therefore, our study findings will contribute to the paucity of evidence on the benefit of antenatal corticosteroids in this group. Health systems should systematically monitor guideline implementations to improve patient outcomes.

Antenatal Corticosteroid Treatment During the Late-Preterm Period and Neonatal Outcomes for Twin Pregnancies

“…17 There has been considerable evidence supporting antenatal corticosteroid treatment during the late-preterm period for singleton pregnancies 11,18,19 but limited, unsupportive evidence for antenatal corticosteroid treatment for twin pregnancies. 12,13 This difference could be explained by the differences in the pharmacokinetics of corticosteroids in twins vs singletons, the off-target phenomenon of antenatal corticosteroids (the absence of delivery Յ7 days after administration of antenatal corticosteroids),…”

“…To minimize the confounding factors in antenatal corticosteroid treatment of individuals with twin pregnancy, we implemented the following strategies. We took advantage of a cohort of 2705 individuals with twin pregnancies, which, to our knowledge, is larger than that of previously reported studies . Instead of the conventional multivariable logistic regression previous studies used, we used the propensity score overlap weighting method to effectively eliminate the potential confounding factors, achieving the effect of randomized clinical trials to the greatest extent possible in retrospective studies .…”

“…The results showed that the use of antenatal corticosteroid treatment was not consistently associated with an improving neonatal respiratory outcome. 12,13 Therefore, the correlation between antenatal corticosteroid treatment for twins at risk of latepreterm birth and neonatal outcomes remains an unanswered question.…”

The role of antenatal corticosteroids in twin pregnancy

“…In several studies including a large multi-center randomized controlled trial, hypoglycemia was noted in late preterm infants whose mothers were treated with ACS (Kamath-Rayne et al, 2012;Gyamfi-Bannerman et al, 2016;Ramadan et al, 2016). The finding was the same in twins as two retrospective cohort studies showed (Ben-David et al, 2020;Vieira et al, 2022). Despite appearing selflimiting, hypoglycemia has been connected to poor neurological outcomes in premature newborns (McKinlay et al, 2017), to which thus attention should be paid.…”

“…A retrospective cohort study including a total of 290 women with twin pregnancies showed that late preterm ACS administration in twins complicated by late preterm birth did not reduce neonatal respiratory morbidity but was associated with higher rates of neonatal intensive care unit (NICU) admission and hypoglycemia ( Ben-David et al, 2020 ). Another study including 1,032 mother-child pairs in twins showed that exposure to ACS is associated with increased odds of hypoglycemia, but no significant association with respiratory complications ( Vieira et al, 2022 ). So far, the results of ACS for late preterm birth of twins have not been very promising.…”