By Ahizechukwu C. Eke, MD, PhD, MPH
Synopsis: The 2021 American College of Obstetricians and Gynecologists/Society for Maternal-Fetal Medicine practice advisory significantly increased the use of antenatal corticosteroids at 22 weeks of gestation in U.S. hospitals planning neonatal resuscitation, highlighting both the powerful influence of clinical guidelines on practice patterns and the persistence of disparities driven by sociodemographic factors.
Source: Fryar C, Liu T, Bates N, et al. Antenatal corticosteroid administration among infants born at 22 weeks’ gestation after a practice advisory endorsing its consideration. Am J Obstet Gynecol MFM. 2025;7(9):101728.
Periviable birth typically is defined as delivery between 20 0/7 and 25 6/7 weeks of gestation, a period that accounts for only about 0.5% of all births yet results in the majority of neonatal deaths and more than 40% of infant deaths.1 Before 23 weeks of gestation, survival is exceedingly rare: only 5% and 6% of neonates born before 23 weeks survive and nearly all survivors experience severe morbidity.1 These previable fetuses represent the extreme end of a broader preterm birth spectrum. Although approximately 12% to 13% of pregnancies in the United States end before 37 weeks, only a small fraction occur at the periviable threshold.2 Preterm deliveries arise from spontaneous labor with intact membranes, preterm premature rupture of membranes, or medically indicated interventions for maternal or fetal indications.2,3 Contributing factors include intrauterine infection or inflammation, vascular disease, uterine overdistension, a history of preterm birth and multiple gestations, and the rising prevalence of medically indicated preterm deliveries.2,3
In the specific context of the 22nd week of gestation, survival remains precarious and clinical decisions are fraught with controversy. Contemporary U.S. population data show that only about 2.5% to 36.5% of live-born infants at 22 to 23 weeks survive, with median survival around 15% at 27 days and 12% at one year.4 The American College of Obstetricians and Gynecologists’ (ACOG) periviable birth consensus emphasizes that prior to 23 weeks of gestation, neonatal survival is exceedingly rare, with a 94% to 95% overall risk of neonatal death. Among infants delivered at 22 weeks (22 0/7 to 22 6/7), 97% to 98% of survivors experience significant neurodevelopmental impairment, and only about 1% survive without impairment.1 Yet, emerging observational studies suggest that administering antenatal corticosteroids together with active neonatal resuscitation may double survival at 22 weeks (~39% vs. 19.5%), although survival without major morbidity remains extremely low (approximately 4% vs. 1%).1
Earlier trials found no significant reduction in mortality or neurodevelopmental impairment when steroids were used before 23 weeks, prompting ACOG to recommend antenatal corticosteroids primarily for imminent delivery at 24 to 25 weeks and to “consider” them at 23 weeks (and now at 22 weeks) only if neonatal resuscitation is planned and thorough counseling has occurred.1 Consequently, practice patterns vary widely across hospitals in the United States, and ethical debates persist over whether to universally resuscitate 22-week-old infants or reserve intensive interventions for selected cases based on parental preferences and institutional resources. In this study, Fryar et al reviewed data regarding the use of the 2021 ACOG practice advisory to determine whether it has been associated with an increase in the use of antenatal corticosteroids among infants born at 22 weeks of gestation in the United States.5
This was a retrospective, secondary analysis of U.S. birth certificate data from the National Vital Statistics System between 2017 and 2023. The study evaluated the effect of the September 2021 ACOG/Society for Maternal-Fetal Medicine (SMFM) practice advisory recommending consideration of antenatal corticosteroid administration at 22 weeks of gestation if neonatal resuscitation was planned. Live births at 22 weeks were the primary focus, with 24- to 25-week births serving as the control group, and 23-week births included in sensitivity analyses. Exclusions were applied for stillbirths, births outside hospitals, non-physician-attended deliveries, congenital anomalies, multiple gestations, extreme birthweights, absence of intrapartum antibiotics (as a proxy for no planned resuscitation), and missing data.
The primary outcome was antenatal corticosteroid use, and the main exposure was the post-guideline period (2022-2023) compared with the pre-guideline era (2017-2020), with 2021 excluded as a washout year. The statistical analysis plan relied on descriptive comparisons and regression modeling to assess changes in antenatal corticosteroid administration before and after the 2021 ACOG practice advisory. Demographics and outcomes were analyzed using standard statistical tests. The primary analysis employed multivariate logistic regression with a difference-in-difference specification to evaluate the interaction between gestational age group (22 weeks vs. 24 to 25 weeks) and time period (pre- vs. post-guideline), adjusting for maternal demographics, obstetric history, and comorbidities. Sensitivity analyses were conducted using 23-week births as the comparator group and linear probability models to estimate percentage point changes.
A total of 11,203 live births at 22 to 25 weeks met inclusion criteria (724 at 22 weeks, 2,688 at 23 weeks, and 7,791 at 24 to 25 weeks). Antenatal steroid use overall was 54% at 22 weeks, 63% at 23 weeks, and 64% at 24 to 25 weeks. At 22 weeks, antenatal corticosteroid administration increased significantly from 48% (178/368) before to 61% (216/356) after the ACOG guideline (P = 0.001). In contrast, rates were unchanged at 23 weeks (63% vs. 65%; P = 0.385) and only slightly higher at 24 to 25 weeks (63% vs. 66%; P = 0.033). Multivariate logistic regression confirmed these findings, showing a 65% higher odds of antenatal corticosteroid administration at 22 weeks after the guideline (adjusted odds ratio [aOR], 1.65; 95% confidence interval [CI], 1.22, 2.22; P = 0.001), while no significant differences were observed at 23 weeks (aOR 1.06; 95% CI, 0.90, 1.26; P = 0.0710) or at 24 to 25 weeks (aOR, 1.10; 95% CI, 0.99, 1.22; P = 0.061).
Sensitivity analyses yielded consistent results. Additional analyses revealed that prenatal care, history of prior preterm birth, hypertensive disorders of pregnancy, labor augmentation, and chorioamnionitis all were associated with higher odds of steroid administration. Notably, non-Hispanic Black women had lower odds of receiving antenatal corticosteroids compared to non-Hispanic white women, highlighting disparities in care.
Commentary
The study found that after the September 2021 ACOG/SMFM practice advisory, antenatal corticosteroid administration at 22 weeks increased meaningfully in U.S. hospital births presumed to plan neonatal resuscitation. Rates were unchanged at 23 weeks and only slightly higher at 24 to 25 weeks, supporting a practice change specific to 22 weeks of gestation. Prenatal care, prior preterm birth, hypertensive disorders of pregnancy, augmentation, and chorioamnionitis were associated with higher odds of antenatal corticosteroid administration. Clinically, the data suggest guidelines can shift behavior even when the recommendation is qualified, and that implementation efforts should pair guidance with focused quality improvement to ensure appropriate, consistent access at 22 weeks.
These findings align with and contextualize the broader antenatal corticosteroid conversation by Jobe and colleagues, which emphasizes that benefits are gestational age-dependent, overall efficacy is variable, and dosing regimens historically are pragmatic rather than pharmacokinetically optimized.6 The Myrhaug et al systematic review and meta-analysis discusses the rapid expansion of antenatal corticosteroid use into periviable gestations (as low as 22 weeks) despite low-certainty evidence at that boundary, and calls for better targeting (accurate dating, true imminence of delivery, and neonatal capability) to avoid overtreatment while preserving benefits for those most likely to benefit from antenatal corticosteroids.7 They also highlight emerging dose-optimization work and remind us that many foundational trials were conducted in high-resource settings, key caveats when translating policy into practice for diverse populations.
Lee, Nelin, and Foglia present the parallel debate on universal vs. selective resuscitation at 22 weeks of gestation.8 Nelin argues that pro-universal experts point to a single-center Swedish study and regional U.S data showing substantially improved survival when active care is standard for all 22-week births, arguing that standardized resuscitation mitigates bias and timing pressures and can achieve survivals approaching those at 23 to 24 weeks in highly resourced systems.8-10 Conversely, Foglia argues that the selective-resuscitation perspective stresses the heterogeneity of outcomes across settings, the high treatment burden, and the need to honor parental values through shared decision-making, noting that pooled survival after active treatment at 22 weeks remains modest, and survival without major in-hospital complications is low in broader cohorts.8 Together, these positions frame the observed U.S. shift in antenatal corticosteroid use at 22 weeks as ethically and operationally complex, and dependent on institutional capability and family-centered counseling.
In conclusion, the Fryar et al study shows that endorsement to consider antenatal corticosteroids at 22 weeks of gestation when resuscitation is planned translated into higher uptake concentrated at that gestation, consistent with evolving periviable practices and the ongoing universal vs. selective resuscitation debate.5 Current ACOG/SMFM guidance recommends a single course of antenatal corticosteroid for patients at risk of preterm birth within seven days at 24 0/7 to 33 6/7 weeks; consideration of antenatal corticosteroids at 22 0/7 to 23 6/7 weeks only when accurate dating, planned neonatal resuscitation, and comprehensive counseling are present; and consideration at 34 0/7 to 36 6/7 weeks for select patients without a prior antenatal steroid course.1 Implementation should be coupled with equitable access, accurate dating, and neonatal intensive care unit readiness, while research refines who benefits most and how to optimize dosing at the threshold of viability.
Ahizechukwu C. Eke, MD, PhD, MPH, is Associate Professor in Maternal Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore.
References
1. American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine. Obstetric Care consensus No. 6: Periviable birth. Obstet Gynecol. 2017;130(4):e187-e199.
2. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75-84.
3. Khandre V, Potdar J, Keerti A. Preterm birth: An overview. Cureus. 2022;14(12):e33006.
4. Vidavalur R, Hussain Z, Hussain N. Association of survival at 22 weeks’ gestation with use of antenatal corticosteroids and mode of delivery in the United States. JAMA Pediatr. 2023;177(1):90-93.
5. Fryar C, Liu T, Bates N, et al. Antenatal corticosteroid administration among infants born at 22 weeks’ gestation after a practice advisory endorsing its consideration. Am J Obstet Gynecol MFM. 2025;7(9):101728.
6. Jobe AH, Goldenberg RL, Kemp MW. Antenatal corticosteroids: An updated assessment of anticipated benefits and potential risks. Am J Obstet Gynecol. 2024;230(3):330-339.
7. Myrhaug HT, Brurberg KG, Hov L, Markestad T. Survival and impairment of extremely premature infants: A meta-analysis. Pediatrics. 2019;143(2):20180933.
8. Lee CD, Nelin L, Foglia EE. Neonatal resuscitation in 22-week pregnancies. N Engl J Med. 2022;386(4):391-393.
9. Backes CH, Söderström F, Ågren J, et al. Outcomes following a comprehensive versus a selective approach for infants born at 22 weeks of gestation. J Perinatol. 2019;39(1):39-47.
10. Watkins PL, Dagle JM, Bell EF, Colaizy TT. Outcomes at 18 to 22 months of corrected age for infants born at 22 to 25 weeks of gestation in a center practicing active management. J Pediatr. 2020;217:52-58.e1.
