Antenatal corticosteroid administration between 24 hours and 7 days before extremely preterm delivery is associated with the lowest rate of mortality

Context

Antenatal corticosteroids (ACS) reduce mortality in preterm infants.¹ The association between timing of ACS and outcomes among extremely preterm infants has been sparsely investigated. In a recent large retrospective cohort study, higher odds for severe neonatal morbidity or mortality were seen in infants born at 24–33 weeks gestation with an administration-to-birth interval of ACS <1 or>7 days compared with 1–7 days.² The objective of this study was to investigate the impact of ACS administration-to-birth interval on survival among extremely preterm infants.

Methods

This population-based cohort study used data collected prospectively from 2004 to 2007. Infants from 220/7 to 266/7 weeks gestation were categorised according to ACS exposure; none; <24 hours; 24 to <48 hours; 48 hours to 7 days; >7 days and unknown duration. The primary outcome was neonatal survival. Secondary outcomes included infant survival and survival without major hospital morbidities. Infants exposed between 48 hours and 7 days were the reference category for analyses. HRs for survival by ACS administration-to-birth interval were estimated using Cox proportional hazards regression analyses. Infant factors associated with higher mortality were included in the model: inborn ≥level 3 hospital, small for gestational age, gender and surfactant <2 hours after birth. However, multiple birth and birth weight were not included.

Findings

There were 707 infants included in this study, of whom 591 (84%) were exposed to ACS, 85 (12%) were unexposed and 31 (4%) had missing data. Infants without exposure had the lowest rate of neonatal survival compared with the reference group (38.8% vs 83.6%; HR 0.22, 95% CI 0.12 to 0.38). Partial exposure was also associated with lower rates of neonatal survival (70.5% vs 83.6%; HR 0.44, 95% CI 0.26 to 0.74). Similarly, infant survival was lowest in infants unexposed to ACS. Infants exposed to a partial course and those delivered >7 days after ACS had lower infant survival but not those delivered 24–47 hours after ACS. Results for survival without major morbidity showed a similar pattern.

Commentary

This study adds to evidence indicating an optimal window for ACS administration from 24 hours to 7 days.^{2 3} Care must be taken interpreting this study in the context of evidence from randomised controlled trials which show reduced mortality following a partial course of ACS.¹ This study did not compare infants without exposure to ACS directly to those with a partial course. A large observational study of infants from 501 to 1500 g with a low rate of ACS exposure found lower mortality among infants with partial exposure.⁴ Although ACS are one of the most effective treatments in preventing death and major morbidities in preterm infants, the mechanism and timing of action remain largely unknown. A recent large multicountry observational study suggested that even administration within 3 hours before delivery can result in higher survival rates in preterm infants.³ The current study noted that the group of infants without ACS exposure was less mature with a higher proportion <24 weeks gestation. Interestingly, this group was also less likely to receive surfactant, suggesting that more infants in this group may not have received full resuscitation. It seems likely there was both antenatal and postnatal bias confounding this study as infants without ACS exposure may have had their care limited.

Implications for practice

The current study supports recommendations that ACS should be given to women at risk of extremely preterm delivery^{5 6} and that ACS administration between 24 hours and 7 days is associated with the lowest mortality rate. However, the best current evidence shows that partial ACS exposure improves survival in preterm infants,¹ possibly even when administered within 3 hours before delivery.³