Previous research has found that children born early have higher risks of neurodevelopmental and behavioural disabilities in the first years of life and throughout childhood and adolescence, but there has been limited research on the long-term outcomes of these children compared with those born at term.
To fill this knowledge gap, researchers from Karolinska Institutet, Stockholm, used Swedish national registry data 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).
Their study of more than 1m children found that those born moderately (32-33 weeks) or late preterm (34-36 weeks), have higher long-term risks of neurodevelopmental difficulties that can affect their behaviour and ability to learn.
As these children comprise about 80% of all preterm births, the researchers said these risks should not be underestimated, adding that their findings may also help professionals and families achieve a better risk assessment and follow-up of these children.
Their findings, published in The British Medical Journal, are based on 1 281 690 singleton children without birth defects born at 32 to 41 weeks between 1998 and 2012, and a sub-group of 349 108 full siblings to control for unmeasured shared genetic and environmental factors.
The main outcomes of interest were movement (motor), brain (cognitive), epileptic, hearing and visual impairments, and a combination of any neurodevelopmental impairment, diagnosed up to the age of 16 years.
Potentially influential factors were taken into account including mother’s age, parity, country of birth, cohabiting status, body mass index during early pregnancy, smoking during pregnancy, diabetic and hypertensive diseases, calendar period of delivery, parents’ educational level and history of neurological and psychiatric disorders, and infant’s sex and birth weight for gestational age.
During an average follow-up period of 13 years, 75 311 infants (48 per 10 000 person years) had at least one diagnosis of any neurodevelopmental impairment.
Some 5 899 (four per 10 000 person years) had motor impairment, 27 371 (17 per 10 000) cognitive impairment, 11 870 (seven per 10 000) epileptic impairment, 19 700 (12 per 10 000) visual impairment, and 20 393 (13 per 10 000) hearing impairment.
Overall, compared with children born full term, those born moderately or late preterm showed higher risks for any impairment (e.g, an additional 475 cases per 10 000 population by age 16 for children born moderately preterm compared with those born full term).
The highest relative risk for children born moderately preterm compared with those born full term was for motor impairment (a nearly five-fold increased risk), followed by epileptic impairment (a nearly two-fold increased risk).
Risks for neurodevelopmental impairments appeared highest from 32 weeks, then gradually declined until 41 weeks, with higher risks also at early term (37-38 weeks) than at full term.
In the sibling comparison analysis, most associations remained stable except for gestational age and epileptic and hearing impairments, where no association was found.
This is an observational study, so can’t establish cause, and the researchers acknowledge that they were unable to provide precise information for some outcomes, and that possible under-reporting or misclassification of the diagnoses might lead to an underestimation of the associations found.
They also can’t rule out the possibility that other unmeasured factors, such as alcohol and substance misuse during pregnancy, may have influenced the results.
However, this was a large, population-based study using high-quality comprehensive national registries, making it possible to investigate clinically relevant risks across the spectrum of gestational age.
As such, they said: “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 to better assess risk, follow-up, and healthcare systems planning for children born moderately or late preterm.”
Study details
Neurological development in children born moderately or late preterm: national cohort study
Ayoub Mitha, Ruoqing Chen Neda Razaz, Stefan Johansson, Olof Stephansson, Maria Altman, Jenny Bolk.
Published in The BMJ on 22 November 2023
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.
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