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Original article
Changes in survival and neurodevelopmental outcomes of infants born at <25 weeks’ gestation: a retrospective observational study in tertiary centres in Japan
  1. Yumi Kono1,
  2. Naohiro Yonemoto2,
  3. Hidehiko Nakanishi3,
  4. Satoshi Kusuda4,
  5. Masanori Fujimura5
  6. on behalf of the the Neonatal Research Network of Japan
  1. 1 Department of Pediatrics, Jichi Medical University, Shimotsuke, Japan
  2. 2 Department of Biostatistics, School of Public Health, Kyoto University, Kyoto, Japan
  3. 3 Department of Neonatology, Maternal and Perinatal Center, Tokyo Women’s Medical University, Tokyo, Japan
  4. 4 Department of Pediatrics, Kyorin Daigaku, Mitaka, Japan
  5. 5 Osaka Women’s and Children’s Hospital, Neonatology, Izumi, Osaka, Japan
  1. Correspondence to Dr Yumi Kono; ykono{at}


Objective To evaluate changes in the outcomes of infants born at <25 weeks’ gestation in the past decade.

Design Retrospective observational study.

Settings A multicentre database of the Neonatal Research Network, Japan.

Patients A total of 3318 infants born at 22–24 weeks’ gestation between periods 1 (2003–2007) and 2 (2008–2012) from 52 tertiary centres.

Main outcome measures We compared death and neurodevelopmental impairments (NDIs) at 3 years of age, including cerebral palsy (CP), visual impairments (VIs), hearing impairments (HIs) and the developmental quotient (DQ) of the Kyoto Scale of Psychological Development test <70, between two periods using multivariate logistic regression analyses adjusted for the centre, gender, multiple gestation, maternal age, caesarean delivery, antenatal steroid use, pregnancy-related hypertension, clinical chorioamnionitis, congenital anomalies and birth weight.

Results A total of 496/1479 infants (34%) in period 1 and 467/1839 (25%) in period 2 died by 3 years of age (adjusted OR 0.70, 95% CIs 0.59 to 0.83). Follow-up data were collected from 631 infants (64% of survivors) in period 1 and 832 (61% of survivors) in period 2. The proportions of CP with Gross Motor Function Classification System ≥2, VI and HI in the infants evaluated were lower, while that of DQ <70 was higher in period 2 than in period 1. Using multiple imputations to account for missing data, death or NDI decreased from 54% in period 1 to 47% in period 2 (0.83, 0.71 to 0.97). Significant decreases were observed in death or CP (0.65, 0.55 to 0.76), death or VI (0.59, 0.50 to 0.69) and death or HI (0.69, 0.58 to 0.81), but not in death or DQ <70 (0.91, 0.78 to 1.06).

Conclusion Along with improved survival, CP, VI and HI, but not cognitive impairments decreased in infants born at <25 weeks’ gestation between the two periods examined in the last decade. Further strategies are needed to reduce cognitive impairments in these infants.

  • neurodevelopment
  • neonatology
  • outcomes research

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  • Contributors YK conceptualised and designed the study and drafted the initial manuscript. NY performed the initial analyses and reviewed and revised the manuscript. HN set up the data and reviewed the manuscript. SK and MF initially conceptualised and designed the database, supervised the study and reviewed the manuscript. All authors agreed to be accountable for all aspects of the work.

  • Competing interests None declared.

  • Patient consent Parental/guardian consent obtained.

  • Ethics approval The study protocol was approved by the Ethics Review Committees of Tokyo Women’s Medical University and Jichi Medical University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data may be open for sharing if required.