By Ahizechukwu C. Eke, MD, PhD, MPH
Associate Professor in Maternal Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore
SYNOPSIS: Prognostic differences exist among neonatal and obstetric care providers when neonates are delivered at 22 weeks of gestation. However, there are no statistically significant differences in the gestational age at which providers recommend active treatment or antenatal corticosteroids.
SOURCE: Nair Shah N, Krishna I, Vyas-Read S, Mangal Patel R. Neonatal and obstetric provider perceptions and management at 22 weeks’ gestation. Am J Perinatol 2022; Dec 15. doi: 10.1055/a-1969-1237. [Online ahead of print].
Fetal viability (the gestational age above which fetuses are sufficiently mature to survive without significant morbidity following delivery) has decreased considerably, from approximately 30-31 weeks of gestation in the 1960s to the current lower limit of 23 weeks of gestation.1 As a result, the lower gestational age at which neonates can be successfully resuscitated in most hospitals across the United States currently is 23 weeks.2 Although this shift represents a significant improvement in our ability to provide prenatal, perinatal, and postnatal care to pregnant women and their offspring, it presents significant management, developmental, ethical, and social challenges.1,3
Management (including timing of antenatal corticosteroids for fetal maturity) and resuscitation of fetuses born at 22 weeks of gestation is challenging and has generated intense debate and disagreements among neonatal and maternal-fetal medicine specialists.4 In addition, the prognosis as perceived by neonatal and obstetric providers can differ and may have an effect on the management and resuscitation of 22-week-old neonates.5
Given the ongoing debate about neonatal resuscitation and management at the 22nd week of gestation, Nair et al designed this study to measure the prognostic discrepancy between provider and data-driven neonatal survival estimates and explore the relationship between prognostic discrepancy and the gestational age threshold at which neonatal providers recommend active management and obstetric providers recommend antenatal corticosteroids.6 This is important, since the definition and approach to management and neonatal resuscitation at the limits of fetal viability are key sources of anxiety to pregnant women and their families.
Healthcare providers (obstetricians and neonatologists) at Atlanta’s Grady Memorial Hospital and Emory University Hospital Midtown neonatal intensive care units completed brief, electronic surveys based on real-life cases managed. The surveys were done between August and September 2020 (neonatologists) and between April and May 2021 (obstetric providers). The electronic surveys were used to acquire provider survival estimates as well as to determine survival criteria at which clinicians would consider active therapy or prenatal corticosteroids. The National Institute of Child Health and Development’s (NICHD) extremely preterm birth outcomes calculator was used to create national survival estimates for fetuses born at 22 weeks of gestation. The authors evaluated the degree of prognostic discrepancy between expected survival rates at 22 weeks of gestation (from the NICHD calculator) and the estimates of survival from obstetric and neonatal providers. To investigate the relationship between prognostic discrepancy at 22 and 23 weeks of gestation, survival estimates at 23 weeks of gestation also were obtained. Prognostic discrepancy rates were classified as optimistic (prognostic discrepancy better than survival estimates), accurate (prognostic discrepancy similar to survival estimates), and pessimistic (prognostic discrepancy worse than survival estimates). Family wishes about resuscitation (if any) also were taken into account.
Non-parametric tests were used to compare the median and interquartile ranges (IQR) of prognostic discrepancies based on responder characteristics. The Kendall-Tau correlation coefficient was used to analyze the relationship between providers’ survival estimations and the survival probability cutoffs at which to propose active therapy or prenatal corticosteroids based on the NICHD calculator. The R2 statistic was used to analyze the correlation between the prognosis discrepancy of cases at 22 and 23 weeks of gestation.
There were 137 neonatal respondents (51% response rate) and 57 obstetric respondents (23% response rate) at the end of the study. Overall, the median prognostic discrepancy rate was 1.5% (IQR, -17, 13). Among all neonatal and obstetric providers, 42 (22%) were optimistic, 100 (52%) were accurate, and 52 (26%) were pessimistic. There were no statistically significant associations between prognostic discrepancy and provider type (P = 0.053), age (P = 0.71), or years of experience (P = 0.41). The median threshold probability of survival below which neonatal and obstetric providers recommended comfort care was 20% (10% to 30%) and 10% (0% to 10%), respectively, while the threshold above which neonatal and obstetric providers recommended active treatment was 30% (20% to 45%) and 10% (10% to 20%), respectively.
Thresholds did not differ among the three prognostic discrepancy groups. By gestational age, neonatal providers unanimously recommended active treatment at ≥ 25 weeks of gestation, and comfort care at ≤ 21 weeks of gestation, while obstetric providers unanimously recommended antenatal corticosteroids at 24 and 25 weeks of gestation and varied in their responses at earlier gestational ages. At 22 weeks of gestation, obstetric provider recommendation for antenatal corticosteroids was 54% when the family was undecided regarding resuscitation and was 81% if the family desired resuscitation. For neonatal providers, there was high positive correlation in prognostic discrepancy for cases at 22 and 23 weeks of gestation (R2 = 0.57).
COMMENTARY
Over time, there has been a gradual decline in the gestational age of fetal viability, since several studies have demonstrated that some neonates born at lower gestational ages (22-23 weeks) can survive.7-9 However, because of the effect of several factors that could affect neonatal and infant growth and development following delivery, it is challenging and very difficult to predict with precision neonatal and infant outcomes after a 22-week delivery.
It is debatable whether to resuscitate every fetus born in the 22nd week of pregnancy.10 For fetuses born at 22 weeks of gestation, targeted rather than universal neonatal resuscitative approaches have been used. The neonatal mortality rate when targeted resuscitation was used was worse than the mortality rate resulting from universal resuscitation (survival, 19% vs. 53%, P = 0.05), despite studies that support the use of a targeted method to resuscitate neonates delivered at 22 weeks of gestation.10 Although it appears that universal resuscitation for all neonates born at 22 weeks of gestation seems logical, the burden of treatment is high, with survivors spending several months in the neonatal intensive care unit (NICU), and they are at high risk for later neurodevelopmental impairment and have very high rates of morbidity and mortality.10
Regarding steroid administration, previous studies showed no discernible decrease in infant death and neurodevelopmental anomalies with the use of prenatal corticosteroids at 20 0/7 weeks to 22 6/7 weeks of gestation.11,12 However, when combined with resuscitative efforts, recent observational studies demonstrate that antenatal corticosteroid administration, in conjunction with resuscitation attempts, improves rates of survival at 22 weeks of gestation.13 Although there is growing information on survival rates for neonates born at 22 weeks of gestation, a major drawback of current studies is that these neonates currently are managed at level IV NICU facilities, making it difficult to generalize the findings from these studies. Additionally, studies frequently combine neonatal outcomes for infants born at 22 weeks of gestation with those for infants born at 23 and 24 weeks of gestation, making it challenging to determine the outcomes for infants born at 22 weeks of gestation. This study had limitations, including a limited sample size, low response rates, closed-ended survey questions, and varied responses on the extent of neonatal resuscitation by providers.
In conclusion, there should be a well-thought-out approach to fetal resuscitation for infants born at 22-23 weeks of gestation after a thorough discussion with patients and their partners. The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine advise that antenatal corticosteroids may be considered at gestational ages between 22 0/7 weeks and 22 6/7 weeks if neonatal resuscitation is planned (after appropriate counseling), but not recommended at gestational ages below 21 6/7 weeks because there is insufficient evidence to support a benefit.13
REFERENCES
- Doyle LW; Victorian Infant Collaborative Study Group. Neonatal intensive care at borderline viability--is it worth it? Early Hum Dev 2004;80:103-113.
- Arzuaga BH, Meadow W. National variability in neonatal resuscitation practices at the limit of viability. Am J Perinatol 2014;31:521-528.
- Shukla A, Beshers C, Worley S, et al. In the grey zone–survival and morbidities of periviable births. J Perinatol 2022;42:1001-1007.
- Swanson JR, Sinkin RA. Antenatal corticosteroids before 24 weeks: Is it time? J Perinatol 2016;36:329-330.
- Holtrop P, Swails T, Riggs T, et al. Resuscitation of infants born at 22 weeks gestation: A 20-year retrospective. J Perinatol 2013;33:222-225.
- Nair Shah N, Krishna I, Vyas-Read S, Mangal Patel R. Neonatal and obstetric provider perceptions and management at 22 weeks’ gestation. Am J Perinatol 2022; Dec 15. doi: 10.1055/a-1969-1237. [Online ahead of print].
- Mehler K, Oberthuer A, Keller T, et al. Survival among infants born at 22 or 23 weeks’ gestation following active prenatal and postnatal care. JAMA Pediatr 2016;170:671-677.
- Ishii N, Kono Y, Yonemoto N, et al. Outcomes of infants born at 22 and 23 weeks’ gestation. Pediatrics 2013;132:62-71.
- Czarny HN, Forde B, DeFranco EA, et al. Association between mode of delivery and infant survival at 22 and 23 weeks of gestation. Am J Obstet Gynecol MFM 2021;3:100340.
- Lee CD, Nelin L, Foglia EE. Neonatal resuscitation in 22-week pregnancies. N Engl J Med 2022;386:391-393.
- American College of Obstetricians and Gynecologists; Society for Maternal-Fetal Medicine. Obstetric Care consensus No. 6: Periviable birth. Obstet Gynecol 2017;130:e187-e199.
- Carlo WA, McDonald SA, Fanaroff AA, et al. Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22 to 25 weeks’ gestation. JAMA 2011;306:2348-2358.
- The American College of Obstetricians and Gynecologists. Use of antenatal corticosteroids at 22 weeks of gestation. Practice Advisory. Reaffirmed October 2022. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2021/09/use-of-antenatal-corticosteroids-at-22-weeks-of-gestation
Prognostic differences exist among neonatal and obstetric care providers when neonates are delivered at 22 weeks of gestation. However, there are no statistically significant differences in the gestational age at which providers recommend active treatment or antenatal corticosteroids.
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