Impact of timing of antenatal corticosteroid exposure on neonatal outcomes

The optimal timing and frequency of antenatal corticosteroids (ACS) administration are still unclear. ACS treatment should be initiated at least 24-48 h prior to delivery to achieve a therapeutic benefit. However, debate exists if the benefits of ACS administration persist more than 7 days after treatment initiation. In fact, if the effects of ACS persist beyond 7 days, then repeated courses of ACS might not be necessary for those delivering after initial treatment. Conversely, if the benefits are temporary, then an additional dose of ACS might be beneficial for those who deliver more than 7 days after initial treatment. Noteworthy, multiple investigations have reported an adverse effect of repeated courses of ACS, with no clear improvement in morbidities.
An American group conducted a retrospective study to determine if women with a remote history of steroid exposure, who then delivered between 30 and 33 6/7 weeks gestation, would have fewer neonatal complications than those with no or limited (<48 h) ACS exposure. Neonatal outcomes after remote or recent ACS exposure were compared as well. Data were stratified by the time interval of ACS administration to delivery: none or <48 h (Incomplete/Unexposed), 48 h to 7 days (Recent) and >7 days (Remote).
In total, 524 infants were included in this analysis: 273 Incomplete/Unexposed, 120 Recent and 131 with Remote ACS exposure. RDS was significantly less frequent with Recent vs. Remote exposure (56.7% vs 69.5%, respectively; p=0.04). In addition, surfactant use was also significantly different between the groups, with infants of the Incomplete/Unexposed group having the highest rate of surfactant use. Statistical analysis show that increasing gestational age [Odds Ratio (OR): 0.68; CI 95%: 0.56-0.83] and Recent ACS exposure (OR: 0.62; CI 95%: 0.39-0.98), but not Remote exposure, were independently associated with a lower incidence of RDS. In addition, surfactant use was significantly less among those infants with Recent (OR: 0.56; CI 95% 0.33-0.97) and Remote (OR: 0.41; 0.23-0.72) steroid exposure. Ventilator use was only reduced in the Remote steroid group (OR: 0.56; CI 95%: 0.35-0.90).
Overall, these results show that infants with ACS exposure >7 days prior to delivery had a significantly increased rate of RDS compared with newborns who were exposed within the 48 h to 7 day window. Moreover, RDS incidence was similar between neonates with limited or no ACS exposure and those with remote steroid exposure. These findings suggest that the beneficial effects of ACS are lost after 1 week or more. Surprisingly, the use of surfactant therapy did not mirror the findings of RDS: in both the Recent and Remote steroid groups the use of surfactant was much lower than in the Incomplete/Unexposed group. A possible explanation of this finding is that the knowledge of prior ACS exposure led the neonatologists to be less aggressive in the practice of surfactant administration. Another possible explanation is that remote steroid exposure may decrease the severity of RDS, but does not impact the frequency of the disease.

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