Elizabeth Roy, Victor Olafusi, Enaja Sambatur, Faezeh Aghajani, Moti Gulersen, Asma Khalil, Vincenzo Berghella, Hiba J. Mustafa

Late Antenatal Corticosteroid Treatment in Twin Pregnancies and Neonatal Outcomes: A Systematic Review and Meta-Analysis

Introduction

Late antenatal corticosteroid treatment in twin pregnancies and neonatal outcomes: a systematic review and meta-analysis. Meta-analysis on late-preterm antenatal corticosteroids in twin pregnancies. Finds no reduced neonatal respiratory complications but increased CPAP & hypoglycemia risk.

Abstract

Objective: To examine the impact of administering late-preterm corticosteroids on neonatal outcomes in twin pregnancies.  Study Design: A systematic review of the literature was conducted in four electronic databases between 2000-2024. Studies reporting on neonatal outcomes in twin pregnancies at risk of preterm birth receiving corticosteroid treatment for fetal lung maturity at the gestational age (GA) of 34 weeks and 0 days to 36 weeks and 6 days were included. Studies involving participants with specific conditions (twin-to-twin transfusion syndrome and intrauterine fetal demise of one fetus) were excluded. The primary outcome was incidence of respiratory distress syndrome (RDS). Secondary outcomes included need for mechanical ventilation, continuous positive airway pressure (CPAP), and neonatal hypoglycemia. Comparison groups included those receiving steroids vs those not. The random effect model was used to generate weighted mean differences (MD) and odds ratio (OR) along with their 95% confidence intervals (CI). Heterogeneity was assessed using the I2 value.   Results: 267 abstracts were screened of which 15 full-texts were fully reviewed. A total of three studies were included in the final analysis which comprised 489 twin pregnancies receiving steroids and 2807 pregnancies not receiving steroids. There were no differences in obstetric characteristics between groups, including maternal age, body mass index, preeclampsia, diabetes, and type of twin chorionicity. GA at delivery was significantly earlier in the steroids group (MD -0.91, 95% CI -1.50 to -0.32). For neonatal outcomes, there were no significant differences in incidence of RDS and need for mechanical ventilation between groups. There were higher chances for CPAP use (OR 2.69, 95% CI, 1.47 to 4.92) and neonatal hypoglycemia (OR 2.05, 95% CI, 1.18 to 3.56) in the steroids group.  Conclusion: This study found that antenatal corticosteroid treatment during the late-preterm period in twin pregnancies was not associated with a reduced risk of neonatal respiratory complications. 

Review

This systematic review and meta-analysis addresses a clinically pertinent question regarding the efficacy and safety of late-preterm antenatal corticosteroids (ACS) in twin pregnancies. Given the rising rates of twin births and the ongoing debate surrounding ACS use in the late-preterm period (34+0 to 36+6 weeks gestation), this study fills an important gap in the literature by specifically focusing on this unique obstetric population. The use of a systematic review and meta-analysis approach promises to synthesize the available evidence and provide a high-level summary of the impact on key neonatal outcomes such as respiratory distress syndrome (RDS), mechanical ventilation, CPAP use, and neonatal hypoglycemia. The methodological rigor of the review is commendable, involving a comprehensive search of four electronic databases spanning over two decades and employing appropriate statistical models for meta-analysis. However, a significant limitation emerges from the results: despite screening 267 abstracts, only three studies were ultimately included in the final analysis. This extremely small number of included studies, representing 489 steroid-exposed and 2807 unexposed twin pregnancies, inherently limits the power and generalizability of the findings. The observation that gestational age at delivery was significantly earlier in the steroid group suggests potential selection bias, where corticosteroids might have been administered to pregnancies perceived to be at higher immediate risk of preterm birth, potentially confounding the outcomes. Critically, the meta-analysis found no reduction in RDS or need for mechanical ventilation with late-preterm ACS, but alarmingly, identified higher chances of CPAP use and neonatal hypoglycemia in the steroid-exposed group. The findings of this review challenge the presumed benefits of late-preterm ACS in twin pregnancies, suggesting not only a lack of positive impact on neonatal respiratory complications but also an increased risk of adverse events like CPAP requirement and neonatal hypoglycemia. This carries significant clinical implications, urging clinicians to reconsider the routine administration of late-preterm ACS in twin pregnancies, particularly given the potential for harm without demonstrable benefit. While the conclusion is compelling, the severe limitation of only three included studies underscores the need for cautious interpretation. Future research must prioritize larger, well-designed randomized controlled trials specifically investigating late-preterm ACS in twin pregnancies to provide more robust evidence and inform clinical guidelines definitively.

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