#392 - [Journal Club] - 📌 Do Antenatal Corticosteroids Improve Survival for Babies Born at 21–24 Weeks?

In this Journal Club episode, Ben and Daphna review a large national cohort study examining the association between antenatal corticosteroid exposure and survival in extremely preterm infants born between 21 and 24 weeks’ gestation. They discuss biologic plausibility, practice variation, and the challenges of interpreting retrospective data, while focusing on how these findings may inform counseling and shared decision-making at the margins of viability.

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The Effects of Antenatal Corticosteroids on Extremely Premature Neonates Born between 21 and 24 Weeks. Yao R, Tritch N, Vedhanayagam K, Ali N, Reimche-Vu H, Gedestad I, Karageuzian S, Contag S.Am J Perinatol. 2025 Nov 6. doi: 10.1055/a-2722-8107. Online ahead of print. PMID: 41086871

Transcript

[00:00.780] Ben: Hello everybody, welcome back to another episode of Journal Club on The Incubator Podcast. We're back today for another article. Daphna, good morning. What do you have in store for us today?

[00:10.824] Daphna: Good morning. I have an article that relates to our discussion from Tuesday. We talked about 21-weekers and touched on antenatal corticosteroids (ACS) at that time. This study, published at the end of last year, is titled "Effects of Antenatal Corticosteroids on Extremely Premature Neonates Born Between 21 and 24 Weeks." It’s from the American Journal of Perinatology. The lead author is Ruafan Yao and the senior author is Stephen Contag, coming out of Loma Linda in California.

[00:51.886] Ben: Yeah, an extension of the discussion on the Iowa paper, looking specifically at the administration of steroids. Very interesting.

[00:54.396] Daphna: Exactly. They wanted to see the impact of antenatal corticosteroids prior to delivery on neonatal outcomes in extremely preterm neonates delivered between 21 and 23 weeks of gestation. As we mentioned, ACOG (American College of Obstetricians and Gynecologists) now suggests we should consider giving steroids at 22 weeks, whereas previously it wasn't recommended before 23 weeks, mostly due to a lack of data.

[01:15.000] Daphna: This was a retrospective cohort study of all live-born, non-anomalous, singleton neonates delivered between 21 0/7 and 23 6/7 weeks at a single Level IV NICU (Neonatal Intensive Care Unit) between 2010 and 2021. They excluded any infants who didn't receive active resuscitation.

[02:00.000] Daphna: They categorized infants into three groups: those who received no steroids, those who received a partial course (one dose), and those who received a complete course (two doses). Their primary outcome was neonatal death, defined as death before NICU discharge. Secondary outcomes included common NICU morbidities like Grade 3 or 4 IVH (Intraventricular Hemorrhage), NEC (Necrotizing Enterocolitis), and BPD (Bronchopulmonary Dysplasia).

[03:00.000] Daphna: During the study period, they had 252 infants meeting the criteria. Interestingly, even at 21 weeks, 18.5% of mothers received some steroids. At 22 weeks, that went up to 48%, and by 23 weeks, it was 90%. This shows that even before formal guidelines changed, clinicians were already "pushing the envelope" based on clinical judgment.

[04:30.000] Ben: It’s that "gray zone" where clinicians feel they have to do something even if the evidence is still catching up. What did the mortality data look like?

[05:43.278] Daphna: The results were striking. For the entire cohort, any exposure to antenatal corticosteroids was associated with a significant reduction in neonatal death. Specifically, the risk of death was 51% for those with no steroids, but dropped to 39.1% with any steroid exposure.

[06:30.000] Daphna: When they broke it down by gestational age, the 22-weekers saw a massive benefit. In the 22-week group, the mortality rate was 53.6% without steroids versus only 33.3% with steroids. Even at 21 weeks, although the sample size was small, there was a trend toward improved survival, though it didn't reach statistical significance for that specific week alone.

[08:00.000] Daphna: Regarding secondary outcomes, they found a significant reduction in the incidence of severe IVH (Grade 3 or 4). In the no-steroid group, the rate was about 34%, compared to only 16% in the group that received a full course of steroids. This is a huge finding because IVH is one of the biggest drivers of long-term neurodevelopmental impairment.

[09:30.000] Ben: Did they see any differences between a partial course and a complete course?

[10:00.000] Daphna: Yes. A complete course was superior to a partial course, but even a partial course (a single dose) provided more protection than no steroids at all. This reinforces the idea that if you think delivery is imminent, you should still give that first dose of betamethasone or dexamethasone.

[11:00.000] Daphna: They also looked at the "steroid-to-delivery interval." The maximum benefit for survival and reduction of IVH was seen when the steroids were administered between 2 and 7 days before delivery. If given less than 24 hours before birth, the benefit was less pronounced but still present.

[12:33.806] Ben: I was discussing this with a family today. It's striking how powerful this intervention can be, specifically for these 22 and 23-weekers. A 51% reduction in the risk of neonatal death compared to 39%—that's a huge difference to a parent.

[12:59.150] Ben: I agree with you. The guidance for the 21st week is still vague, but using shared decision-making with the family and Maternal-Fetal Medicine (MFM), it’s perfectly reasonable to offer steroids based on this emerging data, especially if you have a sense the patient won't make it to 23 weeks.

[13:26.107] Daphna: Absolutely. I'm not a researcher by trade, but it seems like it would be impossible—and perhaps unethical—to do a randomized controlled trial at 21 weeks now, randomizing babies to "no steroids." We have to rely on this high-quality retrospective data.

[13:43.832] Ben: Agreed. Very interesting. Thank you, Daphna. Tomorrow we will be back with our weekly episode of NeoNews tomorrow.