Impact of Preterm Birth on Neurodevelopmental Disorders in South Korea: A Nationwide Population-Based Study

Abstract

Neurodevelopmental disorder (NDD) in preterm infants has become of great interest. We aimed to investigate the impact of preterm birth on the proportion of NDD using nationwide data provided by the Korean National Health Insurance Service. We included 4894 extremely preterm or extremely low-birth-weight (EP/ELBW; <28 weeks of gestation or birth weight < 1000 g) infants, 70,583 other preterm or low-birth-weight (OP/LBW; 28−36 weeks of gestation or birth weight < 2500 g) infants, and 264,057 full-term infants born between 2008 and 2015. We observed their neurodevelopment until 6 years of age or until the year 2019, whichever occurred first. Diagnoses of NDDs were based on the World Health Organization’s International Classification of Diseases 10th revision. An association between preterm birth and NDD was assessed using a multivariable logistic regression model. There was a stepwise increase in the risk of overall NDD with increasing degree of prematurity, from OP/LBW (adjusted odds ratio 4.46; 95% confidence interval 4.34−4.58), to EP/ELBW (16.15; 15.21−17.15). The EP/ELBW group was strongly associated with developmental delay (21.47; 20.05−22.99), cerebral palsy (88.11; 79.89−97.19), and autism spectrum disorder (11.64; 10.37−13.06). Preterm birth considerably increased the risk of NDD by the degree of prematurity.

Keywords: autism spectrum disorder; developmental delay; nationwide cohort; neurodevelopmental disorder; preterm birth.

Figure 1

Flow chart of the study population. Abbreviations: ICD-10, the World Health Organization’s International Classification of Diseases 10th revision; EP, extremely preterm; ELBW, extremely low birth weight; OP, other preterm; LBW, low birth weight; FT, full-term.

Figure 2

Comparisons of the probability of neurodevelopmental disorders in a pediatric population stratified by the degree of prematurity. All subjects are plotted against follow-up years until six years of age. The solid blue line represents the EP/ELBW group, the red dotted line represents the OP/LBW group, and the green dotted line represents the FT group. The x-axis represents follow-up time (year) and the y-axis represents the NDD-free probability. The log-rank test was applied, and p < 0.001 was considered statistically significant. Abbreviations: NDD, neurodevelopmental disorder; EP, extremely preterm; ELBW, extremely low birth weight; OP, other preterm; LBW, low birth weight; FT, full-term; ASD, autism spectrum disorder; ADHD, attention-deficit hyperactivity disorder.