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Original Investigation
September 8, 2015

Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012

Author Affiliations
  • 1Department of Pediatrics, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta, Georgia
  • 2Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina
  • 3Department of Pediatrics, University of Iowa, Iowa City
  • 4Department of Pediatrics, Rainbow Babies and Children’s Hospital, Case Western Reserve University, Cleveland, Ohio
  • 5Division of Neonatology, University of Alabama at Birmingham
  • 6Department of Pediatrics, Wayne State University, Detroit, Michigan
  • 7Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, Rhode Island
  • 8Center for Perinatal Research, Department of Pediatrics, Nationwide Children’s Hospital, The Ohio State University, Columbus
  • 9Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California
  • 10Lucile Packard Children's Hospital, Palo Alto, California
  • 11Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas
  • 12Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville, Maryland
  • 13Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
  • 14Department of Pediatrics, Indiana University School of Medicine, Indianapolis
  • 15Department of Pediatrics, University of Texas Medical School at Houston
  • 16Department of Pediatrics, Duke University, Durham, North Carolina
  • 17University of New Mexico Health Sciences Center, Albuquerque
  • 18University of Rochester School of Medicine and Dentistry, Rochester, New York
  • 19Department of Pediatrics, University of Pennsylvania, Philadelphia
  • 20Department of Pediatrics, Children's Mercy Hospital, Kansas City, Missouri
  • 21Department of Pediatrics, University of California, Los Angeles
  • 22Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
JAMA. 2015;314(10):1039-1051. doi:10.1001/jama.2015.10244

Importance  Extremely preterm infants contribute disproportionately to neonatal morbidity and mortality.

Objective  To review 20-year trends in maternal/neonatal care, complications, and mortality among extremely preterm infants born at Neonatal Research Network centers.

Design, Setting, Participants  Prospective registry of 34 636 infants, 22 to 28 weeks’ gestation, birth weight of 401 to 1500 g, and born at 26 network centers between 1993 and 2012.

Exposures  Extremely preterm birth.

Main Outcomes and Measures  Maternal/neonatal care, morbidities, and survival. Major morbidities, reported for infants who survived more than 12 hours, were severe necrotizing enterocolitis, infection, bronchopulmonary dysplasia, severe intracranial hemorrhage, cystic periventricular leukomalacia, and/or severe retinopathy of prematurity. Regression models assessed yearly changes and were adjusted for study center, race/ethnicity, gestational age, birth weight for gestational age, and sex.

Results  Use of antenatal corticosteroids increased from 1993 to 2012 (24% [348 of 1431 infants]) to 87% (1674 of 1919 infants]; P < .001), as did cesarean delivery (44% [625 of 1431 births] to 64% [1227 of 1921]; P < .001). Delivery room intubation decreased from 80% (1144 of 1433 infants) in 1993 to 65% (1253 of 1922) in 2012 (P < .001). After increasing in the 1990s, postnatal steroid use declined to 8% (141 of 1757 infants) in 2004 (P < .001), with no significant change thereafter. Although most infants were ventilated, continuous positive airway pressure without ventilation increased from 7% (120 of 1666 infants) in 2002 to 11% (190 of 1756 infants) in 2012 (P < .001). Despite no improvement from 1993 to 2004, rates of late-onset sepsis declined between 2005 and 2012 for infants of each gestational age (median, 26 weeks [37% {109 of 296} to 27% {85 of 320}]; adjusted relative risk [RR], 0.93 [95% CI, 0.92-0.94]). Rates of other morbidities declined, but bronchopulmonary dysplasia increased between 2009 and 2012 for infants at 26 to 27 weeks’ gestation (26 weeks, 50% [130 of 258] to 55% [164 of 297]; P < .001). Survival increased between 2009 and 2012 for infants at 23 weeks’ gestation (27% [41 of 152] to 33% [50 of 150]; adjusted RR, 1.09 [95% CI, 1.05-1.14]) and 24 weeks (63% [156 of 248] to 65% [174 of 269]; adjusted RR, 1.05 [95% CI, 1.03-1.07]), with smaller relative increases for infants at 25 and 27 weeks’ gestation, and no change for infants at 22, 26, and 28 weeks’ gestation. Survival without major morbidity increased approximately 2% per year for infants at 25 to 28 weeks’ gestation, with no change for infants at 22 to 24 weeks’ gestation.

Conclusions and Relevance  Among extremely preterm infants born at US academic centers over the last 20 years, changes in maternal and infant care practices and modest reductions in several morbidities were observed, although bronchopulmonary dysplasia increased. Survival increased most markedly for infants born at 23 and 24 weeks’ gestation and survival without major morbidity increased for infants aged 25 to 28 weeks. These findings may be valuable in counseling families and developing novel interventions.

Trial Registration  clinicaltrials.gov Identifier: NCT00063063.