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In the grey zone—survival and morbidities of periviable births

Journal of Perinatology volume 42, pages 1001–1007 (2022)Cite this article

Subjects

Abstract

Objective

To compare the survival and morbidities of infants born between 22 0/7–25 6/7 weeks of gestation.

Study design

This observational cohort study consisted of 187 eligible infants liveborn at a single, Level III Neonatal Intensive Care Unit (NICU) between June 1, 2009, and December 31, 2016, in Cleveland, Ohio. Infants with recognized syndromes or major congenital malformations were excluded from the review.

Result

The rate of survival to discharge for NICU-admitted infants born at 22- and 23- week was 56% and 54% respectively at our institution. There was no trend observed between gestational ages and incidence of necrotizing enterocolitis (NEC), patent ductus arteriousus (PDA), sepsis, or severe intraventricular hemorrhage (IVH- Grade 3 or 4). The infants born at 22 weeks had a higher incidence of retinopathy of prematurity (ROP) as compared to 25 weeks gestation (p < 0.001). The need for home oxygen was significantly higher in the smallest infants 70% at 22 weeks, 62% and 60% at 23 and 24 weeks versus 33% at 25 weeks gestation (p < 0.007). Those born at 22 weeks had the same rate of survival to discharge with severe IVH as those born at 23 weeks but required fewer VP shunts (p > 0.52).

Conclusions

The course of extremely preterm infants shows no difference between those born at 22 and 23 weeks of gestation in our NICU with regards to both mortality and short-term morbidities, although they differed marginally from 24 week gestation infants and significantly from those born at 25 weeks gestation.

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References

  1. Obstetric Care consensus No. 6: Periviable Birth. Obstet Gynecol. 2017;130:e187-e199. https://doi.org/10.1097/aog.0000000000002352.

  2. Doyle LW. Neonatal intensive care at borderline viability-is it worth it? Early Hum Dev. 2004;80:103–13. https://doi.org/10.1016/j.earlhumdev.2004.05.009.

    Article  CAS  PubMed  Google Scholar 

  3. Hack M, Wright LL, Shankaran S, Tyson JE, Horbar JD, Bauer CR, et al. Very-low-birth-weight outcomes of the National Institute of Child Health and Human Development Neonatal Network, November 1989 to October 1990. Am J Obstet Gynecol. 1995;172:457–64. https://doi.org/10.1016/0002-9378(95)90557-x.

    Article  CAS  PubMed  Google Scholar 

  4. Norman M, Hallberg B, Abrahamsson T, Björuklund LJ, Damellöf M, Farooqi A, et al. Association between year of birth and 1-year survival among extremely preterm infants in sweden during 2004–2007 and 2014–2016. JAMA. 2019;321:1188–99. https://doi.org/10.1001/jama.2019.2021.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Stoll BJ, Hansen NI, Bell EF, Shankaran S, Laptook AR, Walsh M, et al. Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network. Pediatrics. 2010;126:443–56. https://doi.org/10.1542/peds.2009-2959.

    Article  PubMed  Google Scholar 

  6. Stoll BJ, Hansen NI, Bell EF, Walsh M, Carlo WA, Shankaran S, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012. JAMA. 2015;314:1039–51. https://doi.org/10.1001/jama.2015.10244.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Younge N, Goldstein RF, Bann CM, Hintz SR, Patel RM, Smith PB, et al. Survival and neurodevelopmental outcomes among periviable infants. N Engl J Med. 2017;376:617–28. https://doi.org/10.1056/NEJMoa1605566.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Söderström F, Normann E, Jonsson M, Ågren J. Outcomes of a uniformly active approach to infants born at 22–24 weeks of gestation. Arch Dis Child Fetal Neonatal Ed. 2021;106:413–7. https://doi.org/10.1136/archdischild-2020-320486.

    Article  PubMed  Google Scholar 

  9. Anderson JG, Baer RJ, Partridge JC, Kuppermann M, Franck LS, Rand L, et al. Survival and major morbidity of extremely preterm infants: a population-based study. Pediatrics. 2016;138, https://doi.org/10.1542/peds.2015-4434.

  10. Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics. 2000;106:659–71. https://doi.org/10.1542/peds.106.4.659.

    Article  CAS  PubMed  Google Scholar 

  11. McElrath TF, Robinson JN, Ecker JL, Ringer SA, Norwitz ER. Neonatal outcome of infants born at 23 weeks’ gestation. Obstet Gynecol. 2001;97:49–52. https://doi.org/10.1016/s0029-7844(00)01086-3.

    Article  CAS  PubMed  Google Scholar 

  12. Stensvold HJ, Klingenberg C, Stoen R, Moster D, Braekke K, Guthe HJ, et al. Neonatal morbidity and 1-year survival of extremely preterm infants. Pediatrics. 2017;139. https://doi.org/10.1542/peds.2016-1821.

  13. Patel RM, Rysavy MA, Bell EF, Tyson JE. Survival of infants born at periviable gestational ages. Clin Perinatol. 2017;44:287–303. https://doi.org/10.1016/j.clp.2017.01.009.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Guinsburg R, Branco de Almeida MF, Dos Santos Rodrigues Sadeck L, Marba STM, Suppo de Souza Rugolo LM, Luz JH, et al. Proactive management of extreme prematurity: disagreement between obstetricians and neonatologists. J Perinatol. 2012;32:913–9. https://doi.org/10.1038/jp.2012.28.

    Article  CAS  PubMed  Google Scholar 

  15. Guillen U, DeMauro S, Ma L, Zupancic J, Wang E, Gafni A, et al. Survival rates in extremely low birthweight infants depend on the denominator: avoiding potential for bias by specifying denominators. Am J Obstet Gynecol. 2011;205:329.e1–7. https://doi.org/10.1016/j.ajog.2011.05.032.

    Article  Google Scholar 

  16. Backes CH, Rivera BK, Haque U, Srouji L, Beck S, Yin H, et al. A proactive approach to neonates born at 23 weeks of gestation. Obstet Gynecol. 2015;126:939–46. https://doi.org/10.1097/aog.0000000000001098.

    Article  PubMed  Google Scholar 

  17. Mehler K, Oberthuer A, Keller T, Becker I, Valter M, Roth B, et al. Survival among infants born at 22 or 23 weeks’ gestation following active prenatal and postnatal care. JAMA Pediatr. 2016;170:671–7. https://doi.org/10.1001/jamapediatrics.2016.0207.

    Article  PubMed  Google Scholar 

  18. Ehret DEY, Edwards EM, Greenberg LT, Bernstein IM, Buzas JS, Soll RF, et al. Association of antenatal steroid exposure with survival among infants receiving postnatal life support at 22 to 25 weeks’ gestation. JAMA Netw Open. 2018;1:e183235. https://doi.org/10.1001/jamanetworkopen.2018.3235.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Rysavy MA, Li L, Bell EF, Das A, Hintz SR, Stoll BJ, et al. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med. 2015;372:1801–11. https://doi.org/10.1056/NEJMoa1410689.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wang D, Yasseen AS 3rd, Marchand-Martin L, Sprague AE, Graves E, Goffinet F, et al. A population-based comparison of preterm neonatal deaths (22–34 gestational weeks) in France and Ontario: a cohort study. CMAJ Open. 2019;7:E159–e166. https://doi.org/10.9778/cmajo.20180199.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Cahill AKA, Kuller J, Turrentine MA. Use of antenatal corticosteroids at 22 weeks of gestation. https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2021/09/use-of-antenatal-corticosteroids-at-22-weeks-of-gestation.

  22. Rysavy MA, Horbar JD, Bell EF, Li L, Greenberg LT, Tyson JE, et al. Assessment of an updated neonatal research network extremely preterm birth outcome model in the Vermont Oxford network. JAMA Pediatr. 2020;174:e196294. https://doi.org/10.1001/jamapediatrics.2019.6294.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Backes CH, Rivera BK, Pavlek L, Beer LJ, Ball MK, Zettler ET, et al. Proactive neonatal treatment at 22 weeks of gestation: a systematic review and meta-analysis. Am J Obstet Gynecol. 2020; https://doi.org/10.1016/j.ajog.2020.07.051.

  24. Roberts G, Anderson PJ, De Luca C, Doyle LW. Changes in neurodevelopmental outcome at age eight in geographic cohorts of children born at 22–27 weeks’ gestational age during the 1990s. Arch Dis Child Fetal Neonatal Ed. 2010;95:F90–4. https://doi.org/10.1136/adc.2009.165480.

    Article  CAS  PubMed  Google Scholar 

  25. Mikkola K, Ritari N, Tommiska V, Salokorpi T, Lehtonen L, Tammela O, et al. Neurodevelopmental outcome at 5 years of age of a national cohort of extremely low birth weight infants who were born in 1996–1997. Pediatrics. 2005;116:1391–400. https://doi.org/10.1542/peds.2005-0171.

    Article  PubMed  Google Scholar 

  26. Drotar D, Hack M, Taylor G, Schluchter M, Andreias L, Klein N. The impact of extremely low birth weight on the families of school-aged children. Pediatrics. 2006;117:2006–13. https://doi.org/10.1542/peds.2005-2118.

    Article  PubMed  Google Scholar 

  27. Stephens BE, Bann CM, Poole WK, Vohr BR. Neurodevelopmental impairment: predictors of its impact on the families of extremely low birth weight infants at 18 months. Infant Ment Health J. 2008;29:570–87. https://doi.org/10.1002/imhj.20196.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Leversen KT, Sommerfelt K, Rønnestad A, Kaaresen PI, Farstad T, Skranes J, et al. Prediction of neurodevelopmental and sensory outcome at 5 years in Norwegian children born extremely preterm. Pediatrics. 2011;127:e630–8. https://doi.org/10.1542/peds.2010-1001.

    Article  PubMed  Google Scholar 

  29. Stahlmann N, Rapp M, Herting E, Thyen U. Outcome of extremely premature infants at early school age: health-related quality of life and neurosensory, cognitive, and behavioral outcomes in a population-based sample in northern Germany. Neuropediatrics. 2009;40:112–9. https://doi.org/10.1055/s-0029-1243166.

    Article  CAS  PubMed  Google Scholar 

  30. Steinmacher J, Pohlandt F, Bode H, Sander S, Kron M, Franz AR. Neurodevelopmental follow-up of very preterm infants after proactive treatment at a gestational age of > or = 23 weeks. J Pediatr. 2008;152:771-6–776.e1-2. https://doi.org/10.1016/j.jpeds.2007.11.004.

    Article  Google Scholar 

  31. Marlow N, Wolke D, Bracewell MA, Samara M. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med. 2005;352:9–19. https://doi.org/10.1056/NEJMoa041367.

    Article  CAS  PubMed  Google Scholar 

  32. Serenius F, Ewald U, Farooqi A, Fellman V, Hafstrom M, Hellgren K, et al. Neurodevelopmental outcomes among extremely preterm infants 6.5 years after active perinatal care in Sweden. JAMA Pediatr. 2016;170:954–63. https://doi.org/10.1001/jamapediatrics.2016.1210.

    Article  PubMed  Google Scholar 

  33. Moore GP, Lemyre B, Barrowman N, Daboval T. Neurodevelopmental outcomes at 4 to 8 years of children born at 22 to 25 weeks’ gestational age: a meta-analysis. JAMA Pediatr. 2013;167:967–74. https://doi.org/10.1001/jamapediatrics.2013.2395.

    Article  PubMed  Google Scholar 

  34. Roberts G, Anderson PJ, Doyle LW. The stability of the diagnosis of developmental disability between ages 2 and 8 in a geographic cohort of very preterm children born in 1997. Arch Dis Child. 2010;95:786–90. https://doi.org/10.1136/adc.2009.160283.

    Article  CAS  PubMed  Google Scholar 

  35. Hack M, Taylor HG, Drotar D, Schluchter M, Carter L, Wilson-Costello D, et al. Poor predictive validity of the Bayley Scales of Infant Development for cognitive function of extremely low birth weight children at school age. Pediatrics. 2005;116:333–41. https://doi.org/10.1542/peds.2005-0173.

    Article  PubMed  Google Scholar 

  36. Saigal S, Stoskopf B, Pinelli J, Streiner D, Hoult L, Paneth N, et al. Self-perceived health-related quality of life of former extremely low birth weight infants at young adulthood. Pediatrics. 2006;118:1140–8. https://doi.org/10.1542/peds.2006-0119.

    Article  PubMed  Google Scholar 

  37. Jaworski M, Janvier A, Lefebvre F, Luu TM. Parental perspectives regarding outcomes of very preterm infants: toward a balanced approach. J Pediatr. 2018;200e1. https://doi.org/10.1016/j.jpeds.2018.03.006.

  38. Saigal S, Stoskopf BL, Feeny D, Furlong W, Burrows E, Rosenbaum PL, et al. Differences in preferences for neonatal outcomes among health care professionals, parents, and adolescents. JAMA. 1999;281:1991–7. https://doi.org/10.1001/jama.281.21.1991.

    Article  CAS  PubMed  Google Scholar 

  39. Lam HS, Wong SP, Liu FY, Wong HL, Fok TF, Ng PC. Attitudes toward neonatal intensive care treatment of preterm infants with a high risk of developing long-term disabilities. Pediatrics. 2009;123:1501–8. https://doi.org/10.1542/peds.2008-2061.

    Article  PubMed  Google Scholar 

  40. Lee SK, Penner PL, Cox M. Comparison of the attitudes of health care professionals and parents toward active treatment of very low birth weight infants. Pediatrics. 1991;88:110–4.

    Article  CAS  Google Scholar 

  41. Janvier A, Baardsnes J, Hebert M, Newell S, Marlow N. Variation of practice and poor outcomes for extremely low gestation births: ordained before birth? Arch Dis Child Fetal Neonatal Ed. 2017;102:F470–f471. https://doi.org/10.1136/archdischild-2017-313332.

    Article  PubMed  Google Scholar 

  42. Lantos JD, Mokalla M, Meadow W. Resource allocation in neonatal and medical ICUs. Epidemiology and rationing at the extremes of life. Am J Respir Crit Care Med. 1997;156:185–9. https://doi.org/10.1164/ajrccm.156.1.9510103.

    Article  CAS  PubMed  Google Scholar 

  43. Meadow W, Lagatta J, Andrews B, Lantos J. The mathematics of morality for neonatal resuscitation. Clin Perinatol. 2012;39:941–56. https://doi.org/10.1016/j.clp.2012.09.013.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Lantos JD, Meadow WL. Costs and end-of-life care in the NICU: lessons for the MICU? J Law Med Ethics. 2011;39:194–200. https://doi.org/10.1111/j.1748-720X.2011.00588.x.

    Article  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Arkansas Children’s Hospital/University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA

    Ankita Shukla & Vikas Chowdhary

  2. Case Western Reserve University, Cleveland, OH, USA

    Caroline Beshers & Marc Collin

  3. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA

    Sarah Worley

  4. Department of Pediatrics, Division of Neonatology, MetroHealth Medical Center- Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Marc Collin

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Shukla, A., Beshers, C., Worley, S. et al. In the grey zone—survival and morbidities of periviable births. J Perinatol 42, 1001–1007 (2022). https://doi.org/10.1038/s41372-022-01355-z

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