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Original Investigation
July 19, 2021

Temporal Trends in Neurodevelopmental Outcomes to 2 Years After Extremely Preterm Birth

Author Affiliations
  • 1Neonatal Services, Royal Women’s Hospital, Melbourne, Australia
  • 2Clinical Sciences, Murdoch Children’s Research Institute, Melbourne, Australia
  • 3Department of Obstetrics & Gynaecology, University of Melbourne, Melbourne, Australia
  • 4Department of Paediatrics, University of Melbourne, Melbourne, Australia
  • 5Clinical Epidemiology and Biostatistics Unit, Murdoch Children’s Research Institute, Melbourne, Australia
  • 6Department of Physiotherapy, University of Melbourne, Melbourne, Australia
  • 7Neonatal Services, Mercy Hospital for Women, Melbourne, Australia
  • 8Department of Neonatology, Monash Medical Centre, Melbourne, Australia
  • 9Department of Nursing, University of Melbourne, Melbourne, Australia
  • 10Paediatric Infant Perinatal Emergency Retrieval, Royal Children’s Hospital, Melbourne, Australia
  • 11Centre for Community and Child Health, Royal Children’s Hospital, Melbourne, Australia
  • 12Population Health, Murdoch Children’s Research Institute, Melbourne, Australia
  • 13Neonatal Medicine, Royal Children’s Hospital, Melbourne, Australia
  • 14Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Melbourne, Australia
JAMA Pediatr. Published online July 19, 2021. doi:10.1001/jamapediatrics.2021.2052
Key Points

Question  Have neurodevelopmental outcomes to 2 years’ corrected age for infants born extremely preterm improved with advances in perinatal and neonatal intensive care?

Findings  In this cohort study of extremely preterm infants at 2 years, survival free of major neurodevelopmental disability increased steadily over time, from 42% in 1991-1992, 51% in 1997, 53% in 2005, to 62% in 2016-2017. Annual numbers of survivors with major neurodevelopmental disability per year were 22 (1991-1992), 39 (1997), 24 (2005), and 26 (2016-2017).

Meaning  In this study, advances in care over time have been associated with increased survival free of major disability at 2 years of age, with no increase in absolute numbers with major neurodevelopmental disability.

Abstract

Importance  Survival of infants born extremely preterm (EP) (<28 weeks’ gestation) has increased since the early 1990s. It is necessary to know whether increased survival is accompanied by increased neurodevelopmental disability.

Objective  To examine changes in major (ie, moderate or severe) neurodevelopmental disability and survival free of major neurodevelopmental disability at 2 years in infants born EP.

Design, Setting, and Participants  Four prospective longitudinal cohort studies comprising all EP live births at 22 to 27 weeks’ gestation from April 1, 2016, to March 31, 2017, and earlier eras (1991-1992, 1997, and 2005), and contemporaneous term-born controls in the state of Victoria, Australia. Among 1208 live births during the periods studied, data were available for analysis of 2-year outcomes in 1152 children: 422 (1991-1992), 215 (1997), 263 (2005), and 252 (2016-2017). Data analysis was performed from September 17, 2020, to April 15, 2021.

Exposures  Extreme preterm live birth.

Main Outcomes and Measures  Survival, blindness, deafness, cerebral palsy, developmental delay, and neurodevelopmental disability at 2 years’ corrected age. Developmental delay comprised a developmental quotient less than −1 SD relative to the control group means on the Bayley Scales for each era. Major neurodevelopmental disability comprised blindness, deafness, moderate to severe cerebral palsy, or a developmental quotient less than −2 SDs. Individual neurodevelopmental outcomes in each era were contrasted relative to the 2016-2017 cohort using logistic regression adjusted for gestational age, sex, birth weight z score, and sociodemographic variables. Changes in survival free of major neurodevelopmental disability over time were also assessed using logistic regression.

Results  Survival to 2 years was highest in 2016-2017 (73% [215 of 293]) compared with earlier eras (1991-1992: 53% [225 of 428]; 1997: 70% [151 of 217]; 2005: 63% [170 of 270]). Blindness and deafness were uncommon (<3%). Cerebral palsy was less common in 2016-2017 (6%) than in earlier eras (1991-1992: 11%; 1997: 12%; 2005: 10%). There were no obvious changes in the rates of developmental quotient less than −2 SDs across eras (1991-1992: 18%; 1997: 22%; 2005: 7%; 2016-2017: 15%) or in rates of major neurodevelopmental disability (1991-1992: 20%; 1997: 26%; 2005: 15%; 2016-2017: 15%). Rates of survival free of major neurodevelopmental disability increased steadily over time: 42% (1991-1992), 51% (1997), 53% (2005), and 62% (2016-2017) (odds ratio, 1.30; 95% CI, 1.15-1.48 per decade; P < .001).

Conclusions and Relevance  These findings suggest that survival free of major disability at age 2 years in children born EP has increased by an absolute 20% since the early 1990s. Increased survival has not been associated with increased neurodevelopmental disability.

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