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?
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%.
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.
Despite improvement during recent decades, extremely preterm infants continue to contribute disproportionately to neonatal mortality and childhood morbidity.
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.
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.
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.
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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.
Corresponding Author: Edward F. Bell, MD, Department of Pediatrics, University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242 (firstname.lastname@example.org).
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.
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