[Skip to Content]
[Skip to Content Landing]

Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018

Educational Objective
To learn about health outcomes associated with preterm delivery.
1 Credit CME
Key Points

Question  Among extremely preterm infants born at US academic medical centers between 2013 and 2018, what were mortality, in-hospital morbidity, and 2-year neurodevelopmental outcomes?

Findings  In this observational study based on a prospective registry of 10 877 infants born at 22-28 weeks’ gestational age in 2013-2018 in 19 US academic medical centers, survival to discharge occurred in 78.3% and was significantly improved compared with a historical rate of 76.0% among infants born in 2008-2012. Among infants born at less than 27 weeks’ gestational age who survived to follow-up assessment at 2 years, 49.9% had been rehospitalized and severe neurodevelopmental impairment occurred in 21.2%.

Meaning  Among extremely preterm infants born at US academic medical centers from 2013 to 2018, survival to discharge significantly improved compared with infants born in 2008-2012, but among those born at less than 27 weeks’ gestational age, rehospitalization and neurodevelopmental impairment at 2 years were common.

Abstract

Importance  Despite improvement during recent decades, extremely preterm infants continue to contribute disproportionately to neonatal mortality and childhood morbidity.

Objective  To review survival, in-hospital morbidities, care practices, and neurodevelopmental and functional outcomes at 22-26 months’ corrected age for extremely preterm infants.

Design, Setting, and Participants  Prospective registry for extremely preterm infants born at 19 US academic centers that are part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. The study included 10 877 infants born at 22-28 weeks’ gestational age between January 1, 2013, and December 31, 2018, including 2566 infants born before 27 weeks between January 1, 2013, and December 31, 2016, who completed follow-up assessments at 22-26 months’ corrected age. The last assessment was completed on August 13, 2019. Outcomes were compared with a similar cohort of infants born in 2008-2012 adjusting for gestational age.

Exposures  Extremely preterm birth.

Main Outcomes and Measures  Survival and 12 in-hospital morbidities were assessed, including necrotizing enterocolitis, infection, intracranial hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia. Infants were assessed at 22-26 months’ corrected age for 12 health and functional outcomes, including neurodevelopment, cerebral palsy, vision, hearing, rehospitalizations, and need for assistive devices.

Results  The 10 877 infants were 49.0% female and 51.0% male; 78.3% (8495/10848) survived to discharge, an increase from 76.0% in 2008-2012 (adjusted difference, 2.0%; 95% CI, 1.0%-2.9%). Survival to discharge was 10.9% (60/549) for live-born infants at 22 weeks and 94.0% (2267/2412) at 28 weeks. Survival among actively treated infants was 30.0% (60/200) at 22 weeks and 55.8% (535/958) at 23 weeks. All in-hospital morbidities were more likely among infants born at earlier gestational ages. Overall, 8.9% (890/9956) of infants had necrotizing enterocolitis, 2.4% (238/9957) had early-onset infection, 19.9% (1911/9610) had late-onset infection, 14.3% (1386/9705) had severe intracranial hemorrhage, 12.8% (1099/8585) had severe retinopathy of prematurity, and 8.0% (666/8305) had severe bronchopulmonary dysplasia. Among 2930 surviving infants with gestational ages of 22-26 weeks eligible for follow-up, 2566 (87.6%) were examined. By 2-year follow-up, 8.4% (214/2555) of children had moderate to severe cerebral palsy, 1.5% (38/2555) had bilateral blindness, 2.5% (64/2527) required hearing aids or cochlear implants, 49.9% (1277/2561) had been rehospitalized, and 15.4% (393/2560) required mobility aids or other supportive devices. Among 2458 fully evaluated infants, 48.7% (1198/2458) had no or mild neurodevelopmental impairment at follow-up, 29.3% (709/2419) had moderate neurodevelopmental impairment, and 21.2% (512/2419) had severe neurodevelopmental impairment.

Conclusions and Relevance  Among extremely preterm infants born in 2013-2018 and treated at 19 US academic medical centers, 78.3% survived to discharge, a significantly higher rate than for infants born in 2008-2012. Among infants born at less than 27 weeks’ gestational age, rehospitalization and neurodevelopmental impairment were common at 2 years of age.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 Credit(s)™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Edward F. Bell, MD, Department of Pediatrics, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242 (edward-bell@uiowa.edu).

Correction: This article was corrected on June 7, 2022, for a technical problem in Supplement 2.

Accepted for Publication: December 10, 2021.

Author Contributions: Ms Hansen and Dr Das had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Bell, Hintz, Vohr, Stoll, Rysavy.

Acquisition, analysis, or interpretation of data: Bell, Hintz, Hansen, Bann, Wyckoff, DeMauro, Walsh, Stoll, Carlo, Van Meurs, Rysavy, Patel, Merhar, Sánchez, Laptook, Hibbs, Cotten, D’Angio, Winter, Fuller, Das.

Drafting of the manuscript: Bell, Hintz, Vohr.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Hansen, Bann, Das.

Obtained funding: Bell, Wyckoff, Walsh, Stoll, Van Meurs, Patel, Merhar, Sánchez, Hibbs, D’Angio, Das.

Administrative, technical, or material support: Hintz, Wyckoff, Stoll, Carlo, Van Meurs, Sánchez, Hibbs.

Supervision: Bell, Hintz, Wyckoff, Van Meurs, Sánchez, Hibbs, Cotten, D’Angio, Das.

Conflict of Interest Disclosures: Drs Bell, Hintz, Walsh, Vohr, Rysavy, Merhar, Laptook, Hibbs, and Fuller reported receiving grant(s) from the National Institutes of Health (NIH) outside the submitted work. Dr DeMauro reported receiving grants from the NIH outside the submitted work and a grant from the Thrasher Research Fund. Dr Carlo reported receiving grants from the NIH outside the submitted work and grants from the Thrasher Research Fund, the University of Virginia, the Hudson Alpha Institute for Biotechnology, the Foundation for the National Institutes of Health, and the Gates Foundation. Dr Van Meurs reported receiving grants from the NIH outside the submitted work and grants from the Thrasher Foundation and serving on a scientific advisory board for Greenwich Biosciences. Dr Patel reported serving on the data monitoring committee for a trial by Infant Bacterial Therapeutics/Premier Research. Dr Sánchez reported receiving grants from Merck and AstraZeneca (MedImmune). Dr Cotten reported receiving grants from the NIH outside the submitted work and a grant from the Robertson Foundation. No other disclosures were reported.

Funding/Support: The NIH, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Center for Research Resources, and the National Center for Advancing Translational Sciences provided grant support for the Neonatal Research Network Generic Database and Follow-up studies to maintain high-risk preterm infant registries through the following cooperative agreements: U10 HD021373, UG1 HD021364, UG1 HD021385, UG1 HD027851, UG1 HD027853, UG1 HD027856, UG1 HD027880, UG1 HD027904, UG1 HD034216, UG1 HD036790, UG1 HD040492, UG1 HD040689, UG1 HD053089, UG1 HD053109, UG1 HD068244, UG1 HD068263, UG1 HD068270, UG1 HD068278, UG1 HD068284, UG1 HD087226, UG1 HD087229, UL1 TR000006, UL1 TR000041, UL1 TR000042, UL1 TR000077, UL1 TR000093, UL1 TR000105, UL1 TR000442, UL1 TR000454, and UL1 TR001117.

Role of the Funder/Sponsor: Eunice Kennedy Shriver National Institute of Child Health staff had input into the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The members of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network appear in Supplement 2.

Disclaimer: The content of the article is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Additional Contributions: Participating Neonatal Research Network sites collected data and transmitted them to RTI International, the data coordinating center for the network, which stored, managed, and analyzed the data for this study. We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study.

References
1.
Stoll  BJ , Hansen  NI , Bell  EF ,  et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012.   JAMA. 2015;314(10):1039-1051. doi:10.1001/jama.2015.10244PubMedGoogle ScholarCrossref
2.
Horbar  JD , Edwards  EM , Greenberg  LT ,  et al.  Variation in performance of neonatal intensive care units in the United States.   JAMA Pediatr. 2017;171(3):e164396. doi:10.1001/jamapediatrics.2016.4396PubMedGoogle ScholarCrossref
3.
Lee  SK , Beltempo  M , McMillan  DD ,  et al; Evidence-Based Practice for Improving Quality Investigators.  Outcomes and care practices for preterm infants born at less than 33 weeks’ gestation: a quality-improvement study.   CMAJ. 2020;192(4):E81-E91. doi:10.1503/cmaj.190940PubMedGoogle ScholarCrossref
4.
Kono  Y , Yonemoto  N , Nakanishi  H , Kusuda  S , Fujimura  M .  Changes in survival and neurodevelopmental outcomes of infants born at <25 weeks’ gestation: a retrospective observational study in tertiary centres in Japan.   BMJ Paediatr Open. 2018;2(1):e000211. doi:10.1136/bmjpo-2017-000211PubMedGoogle ScholarCrossref
5.
Norman  M , Hallberg  B , Abrahamsson  T ,  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(12):1188-1199. doi:10.1001/jama.2019.2021PubMedGoogle ScholarCrossref
6.
Younge  N , Goldstein  RF , Bann  CM ,  et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Survival and neurodevelopmental outcomes among periviable infants.   N Engl J Med. 2017;376(7):617-628. doi:10.1056/NEJMoa1605566PubMedGoogle ScholarCrossref
7.
Synnes  A , Luu  TM , Moddemann  D ,  et al; Canadian Neonatal Network and the Canadian Neonatal Follow-up Network.  Determinants of developmental outcomes in a very preterm Canadian cohort.   Arch Dis Child Fetal Neonatal Ed. 2017;102(3):F235-F234. doi:10.1136/archdischild-2016-311228PubMedGoogle ScholarCrossref
8.
Adams-Chapman  I , Heyne  RJ , DeMauro  SB ,  et al; Follow-up Study of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Neurodevelopmental impairment among extremely preterm infants in the Neonatal Research Network.   Pediatrics. 2018;141(5):e20173091. doi:10.1542/peds.2017-3091PubMedGoogle ScholarCrossref
9.
Cheong  JLY , Anderson  PJ , Burnett  AC ,  et al; Victorian Infant Collaborative Study Group.  Changing neurodevelopment at 8 years in children born extremely preterm since the 1990s.   Pediatrics. 2017;139(6):e20164086. doi:10.1542/peds.2016-4086PubMedGoogle ScholarCrossref
10.
Moore  T , Hennessy  EM , Myles  J ,  et al.  Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies.   BMJ. 2012;345:e7961. doi:10.1136/bmj.e7961Google ScholarCrossref
11.
Marlow  N , Doyle  LW , Anderson  P ,  et al; International Neonatal Consortium.  Assessment of long-term neurodevelopmental outcome following trials of medicinal products in newborn infants.   Pediatr Res. 2019;86(5):567-572. doi:10.1038/s41390-019-0526-1PubMedGoogle ScholarCrossref
12.
Janvier  A , Farlow  B , Baardsnes  J , Pearce  R , Barrington  KJ .  Measuring and communicating meaningful outcomes in neonatology: a family perspective.   Semin Perinatol. 2016;40(8):571-577. doi:10.1053/j.semperi.2016.09.009PubMedGoogle ScholarCrossref
13.
Saigal  S , Ferro  MA , Van Lieshout  RJ , Schmidt  LA , Morrison  KM , Boyle  MH .  Health-related quality of life trajectories of extremely low birth weight survivors into adulthood.   J Pediatr. 2016;179(Dec):68-73. doi:10.1016/j.jpeds.2016.08.018PubMedGoogle ScholarCrossref
14.
McAndrew  S , Acharya  K , Westerdahl  J ,  et al.  A prospective study of parent health-related quality of life before and after discharge from the neonatal intensive care unit.   J Pediatr. 2019;213(Oct):38-45. doi:10.1016/j.jpeds.2019.05.067PubMedGoogle ScholarCrossref
15.
Engle  WA ; American Academy of Pediatrics Committee on Fetus and Newborn.  Age terminology during the perinatal period.   Pediatrics. 2004;114(5):1362-1364. doi:10.1542/peds.2004-1915PubMedGoogle ScholarCrossref
16.
Travers  CP , Carlo  WA , McDonald  SA ,  et al; Generic Database and Follow-up Subcommittees of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Racial/ethnic disparities among extremely preterm infants in the United States from 2002 to 2016.   JAMA Netw Open. 2020;3(6):e206757. doi:10.1001/jamanetworkopen.2020.6757PubMedGoogle ScholarCrossref
17.
Alexander  GR , Himes  JH , Kaufman  RB , Mor  J , Kogan  M .  A United States national reference for fetal growth.   Obstet Gynecol. 1996;87(2):163-168. doi:10.1016/0029-7844(95)00386-XPubMedGoogle ScholarCrossref
18.
Bell  MJ , Ternberg  JL , Feigin  RD ,  et al.  Neonatal necrotizing enterocolitis: therapeutic decisions based upon clinical staging.   Ann Surg. 1978;187(1):1-7. doi:10.1097/00000658-197801000-00001PubMedGoogle ScholarCrossref
19.
Walsh  MC , Kliegman  RM .  Necrotizing enterocolitis: treatment based on staging criteria.   Pediatr Clin North Am. 1986;33(1):179-201. doi:10.1016/S0031-3955(16)34975-6PubMedGoogle ScholarCrossref
20.
Papile  LA , Burstein  J , Burstein  R , Koffler  H .  Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm.   J Pediatr. 1978;92(4):529-534. doi:10.1016/S0022-3476(78)80282-0PubMedGoogle ScholarCrossref
21.
Jensen  EA , Dysart  K , Gantz  MG ,  et al.  The diagnosis of bronchopulmonary dysplasia in very preterm infants: an evidence-based approach.   Am J Respir Crit Care Med. 2019;200(6):751-759. doi:10.1164/rccm.201812-2348OCPubMedGoogle ScholarCrossref
22.
Rysavy  MA , Li  L , Bell  EF ,  et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Between-hospital variation in treatment and outcomes in extremely preterm infants.   N Engl J Med. 2015;372(19):1801-1811. doi:10.1056/NEJMoa1410689PubMedGoogle ScholarCrossref
23.
Bayley  N.   Bayley Scales of Infant and Toddler Development, Third Edition. Harcourt Assessment; 2006.
24.
Newman  JE , Bann  CM , Vohr  BR , Dusick  AM , Higgins  RD ; Follow-up Study Group of Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  Improving the Neonatal Research Network annual certification for neurologic examination of the 18-22 month child.   J Pediatr. 2012;161(6):1041-1046. doi:10.1016/j.jpeds.2012.05.048PubMedGoogle ScholarCrossref
25.
Palisano  R , Rosenbaum  P , Walter  S , Russell  D , Wood  E , Galuppi  B .  Development and reliability of a system to classify gross motor function in children with cerebral palsy.   Dev Med Child Neurol. 1997;39(4):214-223. doi:10.1111/j.1469-8749.1997.tb07414.xPubMedGoogle ScholarCrossref
26.
Spiegelman  D , Hertzmark  E .  Easy SAS calculations for risk or prevalence ratios and differences.   Am J Epidemiol. 2005;162(3):199-200. doi:10.1093/aje/kwi188PubMedGoogle ScholarCrossref
27.
Haslam  MD , Lisonkova  S , Creighton  D ,  et al; Canadian Neonatal Network and the Canadian Neonatal Follow-up Network.  Severe neurodevelopmental impairment in neonates born preterm: impact of varying definitions in a Canadian cohort.   J Pediatr. 2018;197(Jun):75-81. doi:10.1016/j.jpeds.2017.12.020PubMedGoogle ScholarCrossref
28.
Serenius  F , Källén  K , Blennow  M ,  et al; EXPRESS Group.  Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in Sweden.   JAMA. 2013;309(17):1810-1820. doi:10.1001/jama.2013.3786PubMedGoogle ScholarCrossref
29.
Jaworski  M , Janvier  A , Lefebvre  F , Luu  TM .  Parental perspectives regarding outcomes of very preterm infants: toward a balanced approach.   J Pediatr. 2018;200:58-63. doi:10.1016/j.jpeds.2018.03.006PubMedGoogle ScholarCrossref
30.
Daly  M .  Parental perspective on neonatal outcomes.   BMJ Paediatr Open. 2019;3(1):e000404. doi:10.1136/bmjpo-2018-000404PubMedGoogle ScholarCrossref
31.
Bangma  JT , Kwiatkowski  E , Psioda  M ,  et al.  Assessing positive child health among individuals born extremely preterm.   J Pediatr. 2018;202(Nov):44-49. doi:10.1016/j.jpeds.2018.06.037PubMedGoogle ScholarCrossref
32.
Lamarche-Vadel  A , Blondel  B , Truffer  P ,  et al; EPIPAGE Study Group.  Re-hospitalization in infants younger than 29 weeks’ gestation in the EPIPAGE cohort.   Acta Paediatr. 2004;93(10):1340-1345. doi:10.1111/j.1651-2227.2004.tb02934.xPubMedGoogle ScholarCrossref
33.
DeMauro  SB , Jensen  EA , Bann  CM ,  et al.  Home oxygen and 2-year outcomes of preterm infants with bronchopulmonary dysplasia.   Pediatrics. 2019;143(5):e20182956. doi:10.1542/peds.2018-2956PubMedGoogle ScholarCrossref
34.
Rysavy  MA , Colaizy  TT , Bann  CM ,  et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.  The relationship of neurodevelopmental impairment to concurrent early childhood outcomes of extremely preterm infants.   J Perinatol. 2021;41(9):2270-2278. doi:10.1038/s41372-021-00999-7PubMedGoogle ScholarCrossref
35.
Ehret  DEY , Edwards  EM , Greenberg  LT ,  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(6):e183235. doi:10.1001/jamanetworkopen.2018.3235PubMedGoogle ScholarCrossref
36.
Taylor  GL , Joseph  RM , Kuban  KCK ,  et al.  Changes in neurodevelopmental outcomes from age 2 to 10 years for children born extremely preterm.   Pediatrics. 2021;147(5):e2020001040. doi:10.1542/peds.2020-001040PubMedGoogle ScholarCrossref
37.
Marlow  N .  Is survival and neurodevelopmental impairment at 2 years of age the gold standard outcome for neonatal studies?   Arch Dis Child Fetal Neonatal Ed. 2015;100(1):F82-F84. doi:10.1136/archdischild-2014-306191PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
Want full access to the AMA Ed Hub?
After you sign up for AMA Membership, make sure you sign in or create a Physician account with the AMA in order to access all learning activities on the AMA Ed Hub
Buy this activity
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Close
Close

Lookup An Activity

or

My Saved Searches

You currently have no searches saved.

Close

My Saved Courses

You currently have no courses saved.

Close