Neurological development in children born moderately or late preterm: national cohort study

Abstract

Objective: To assess long term neurodevelopmental outcomes of children born at different gestational ages, particularly 32-33 weeks (moderately preterm) and 34-36 weeks (late preterm), compared with 39-40 weeks (full term).

Design: Nationwide cohort study.

Setting: Sweden.

Participants: 1 281 690 liveborn singleton children without congenital malformations born at 32⁺⁰ to 41⁺⁶ weeks between 1998 and 2012.

Main outcome measures: The primary outcomes of interest were motor, cognitive, epileptic, hearing, and visual impairments and a composite of any neurodevelopmental impairment, diagnosed up to age 16 years. Hazard ratios and 95% confidence intervals were estimated using Cox regression adjusted for parental and infant characteristics in the study population and in the subset of full siblings. Risk differences were also estimated to assess the absolute risk of neurodevelopmental impairment.

Results: During a median follow-up of 13.1 years (interquartile range 9.5-15.9 years), 75 311 (47.8 per 10 000 person years) liveborn singleton infants without congenital malformations had at least one diagnosis of any neurodevelopmental impairment: 5899 (3.6 per 10 000 person years) had motor impairment, 27 371 (17.0 per 10 000 person years) cognitive impairment, 11 870 (7.3 per 10 000 person years) epileptic impairment, 19 700 (12.2 per 10 000 person years) visual impairment, and 20 393 (12.6 per 10 000 person years) hearing impairment. Children born moderately or late preterm, compared with those born full term, showed higher risks for any impairment (hazard ratio 1.73 (95% confidence interval 1.60 to 1.87) and 1.30 (1.26 to 1.35); risk difference 4.75% (95% confidence interval 3.88% to 5.60%) and 2.03% (1.75% to 2.35%), respectively) as well as motor, cognitive, epileptic, visual, and hearing impairments. Risks for neurodevelopmental impairments appeared highest from 32 weeks (the earliest gestational age), gradually declined until 41 weeks, and were also higher at 37-38 weeks (early term) compared with 39-40 weeks. In the sibling comparison analysis (n=349 108), most associations remained stable except for gestational age and epileptic and hearing impairments, where no association was observed; for children born early term the risk was only higher for cognitive impairment compared with those born full term.

Conclusions: The findings of this study suggest that children born moderately or late preterm have higher risks of adverse neurodevelopmental outcomes. The risks should not be underestimated as these children comprise the largest proportion of children born preterm. The findings may help professionals and families achieve a better risk assessment and follow-up.

Fig 1

Association between gestational age and neurodevelopmental outcomes among liveborn singleton children without congenital malformations in Sweden 1998-2012. Risk difference is the difference in risk of neurodevelopmental outcome by age 16 years comparing different gestational ages. Hazard ratios and risk differences are adjusted for maternal age at delivery, parity, country of birth, cohabiting status, body mass index during early pregnancy, smoking during pregnancy, diabetic and hypertensive diseases, calendar period of delivery, parental highest educational level, parental history of neurological or psychiatric disorder, and infant’s sex and birth weight for gestational age. Children born at 40⁺⁰ weeks are the reference. Any impairment was defined by at least one of the following: motor, cognitive, epileptic, visual, or hearing impairment. Any severe or major impairment was defined by a diagnosis of cerebral palsy, severe mental retardation, generalised epileptic disorder, or severe hearing or visual impairment