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Original Investigation
March 2, 2020

Assessment of an Updated Neonatal Research Network Extremely Preterm Birth Outcome Model in the Vermont Oxford Network

Author Affiliations
  • 1Stead Family Department of Pediatrics, University of Iowa, Iowa City
  • 2Vermont Oxford Network, Burlington
  • 3Department of Pediatrics, University of Vermont College of Medicine, Burlington
  • 4Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, North Carolina
  • 5Center for Clinical Research & Evidence-Based Medicine, University of Texas McGovern Medical School, Houston
  • 6Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia
  • 7Department of Pediatrics, University of Alabama, Birmingham
  • 8Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
  • 9Department of Mathematics and Statistics, College of Engineering and Mathematical Sciences, University of Vermont, Burlington
  • 10Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California
  • 11Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio
  • 12Biostatistics and Epidemiology Division, RTI International, Rockville, Maryland
  • 13Office of Research, George Mason University College of Health and Human Services, Fairfax, Virginia
JAMA Pediatr. Published online March 2, 2020. doi:10.1001/jamapediatrics.2019.6294
Key Points

Question  Do differences in infant survival among hospitals and over time affect a prognostic model widely used in extremely preterm birth counseling?

Findings  In this prognostic study of most actively treated extremely preterm infants in the United States in 2006 to 2012 and 2013 to 2016, survival increased from 66% to 70%, and model prediction was moderate. The birth hospital and gestational age contributed equally to prediction of survival .

Meaning  For extremely preterm birth, an area of medicine with substantial variation among hospitals and changing outcomes, prognostic models used in clinical practice may require accounting for local outcomes and periodic updating to remain relevant.


Importance  The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) extremely preterm birth outcome model is widely used for prognostication by practitioners caring for families expecting extremely preterm birth. The model provides information on mean outcomes from 1998 to 2003 and does not account for substantial variation in outcomes among US hospitals.

Objective  To update and validate the NRN extremely preterm birth outcome model for most extremely preterm infants in the United States.

Design, Setting, and Participants  This prognostic study included 3 observational cohorts from January 1, 2006, to December 31, 2016, at 19 US centers in the NRN (derivation cohort) and 637 US centers in Vermont Oxford Network (VON) (validation cohorts). Actively treated infants born at 22 weeks’ 0 days’ to 25 weeks’ 6 days’ gestation and weighing 401 to 1000 g, including 4176 in the NRN for 2006 to 2012, 45 179 in VON for 2006 to 2012, and 25 969 in VON for 2013 to 2016, were studied. VON cohorts comprised more than 85% of eligible US births. Data analysis was performed from May 1, 2017, to March 31, 2019.

Exposures  Predictive variables used in the original model, including infant sex, birth weight, plurality, gestational age at birth, and exposure to antenatal corticosteroids.

Main Outcomes and Measures  The main outcome was death before discharge. Secondary outcomes included neurodevelopmental impairment at 18 to 26 months’ corrected age and measures of hospital resource use (days of hospitalization and ventilator use).

Results  Among 4176 actively treated infants in the NRN cohort (48% female; mean [SD] gestational age, 24.2 [0.8] weeks), survival was 63% vs 62% among 3702 infants in the era of the original model (47% female; mean [SD] gestational age, 24.2 [0.8] weeks). In the concurrent (2006-2012) VON cohort, survival was 66% among 45 179 actively treated infants (47% female; mean [SD] gestational age, 24.1 [0.8] weeks) and 70% among 25 969 infants from 2013 to 2016 (48% female; mean [SD] gestational age, 24.1 [0.8] weeks). Model C statistics were 0.74 in the 2006-2012 validation cohort and 0.73 in the 2013-2016 validation cohort. With the use of decision curve analysis to compare the model with a gestational age–only approach to prognostication, the updated model showed a predictive advantage. The birth hospital contributed equally as much to prediction of survival as gestational age (20%) but less than the other factors combined (60%).

Conclusions and Relevance  An updated model using well-known factors to predict survival for extremely preterm infants performed moderately well when applied to large US cohorts. Because survival rates change over time, the model requires periodic updating. The hospital of birth contributed substantially to outcome prediction.

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