Developmental Trajectories in Very Preterm Born Children Up to 8 Years: A Longitudinal Cohort Study

Abstract

Aim: Long-term outcome data in preterm children is often limited to cross-sectional measurement of neurodevelopmental impairment (NDI) at the corrected age of 24-36 months. However, impairments may only become overt during childhood or resolve with time, and individual trajectories in outcome over time may vary. The primary aim of this study was to describe NDI in very preterm born children at three subsequent ages of 2, 5, and 8 years of age. As a secondary aim, a longitudinal analysis was performed on the individual longitudinal trajectories in NDI from 2 to 8 years of age. Methods: Single-center prospective cohort study including children born between 1990 and 2011 below 30 weeks' gestation and followed into 2019. The outcome measurement was NDI assessed at 2, 5, and 8 years of age. NDI is a composite score that includes cognitive, neurological, visual, and auditory functions, in which problems were categorized as none, mild, moderate, or severe. Cognitive function measured as total DQ/IQ score was assessed by standardized psychometric tests. Neurological, visual, and auditory functions were assessed by the neonatologist. Results: In total, 921 children were eligible for follow-up, of whom 726 (79%) children were assessed. No NDI was seen in 54, 54, and 62%, mild NDI was seen in 31, 36, and 30%, and moderate-to-severe NDI was seen in 15, 9.2, and 8.6% of the children at 2, 5, and 8 years, respectively. From 2 to 8 years, 63% of the children remained in the same NDI category, 20% of the children improved to a better NDI category, and 17% deteriorated toward a worse NDI category. No differences were found in baseline characteristics of infants that improved or deteriorated. Extreme prematurity, male gender and low parental education were associated with worse NDI status at all time points. Although we observed considerable individual variation over time in NDI status, the course of the trajectories in NDI were not associated with gestation, gender, and parental education. Conclusions: Continued follow-up until school life is essential in order to provide optimal and individually focused referrals and care when needed.

Keywords: NDI; longitudinal follow-up; neurodevelopmental outcome; trajectories; very preterm children.

Figure 1

Flowchart of the included children. 921 children were eligible for follow-up at the outpatient clinic. In total, the results are based on 726 participants with data on 1930 follow-up moments, as presented in the gray square.

Figure 2

Shifts in NDI from 2 to 8 years of age. This figure shows NDI rate at 2 vs. 8 years of age for infants with NDI calculation at all three follow-up contacts (N = 495). The numbers are presented as N (%), with the % calculated relatively to the full group of N = 495 infants. The row sums show the total number of infants at 2 years of age for normal, mild, and moderate-to-severe NDI. The column sums show the total number of infants at 8 years of age for normal, mild, and moderate-to-severe NDI. The dark gray boxes represent all infants that deteriorated toward a worse NDI category from 2 to 8 years, the light gray boxed represent all infants that improved toward a better NDI category from 2 to 8 years, and the white boxes represent all infants that remained in the same NDI category.

Figure 3

Individual trajectories of neurodevelopmental impairment (NDI) at different ages, presented in a horizontal line plot for all children with follow-up. The horizontal line plot uses colors to differentiate between states on a categorical longitudinal variable for multiple participants. Because categorical data defines a specific state, a trajectory for a categorical variable becomes a sequence of states rather than a continuum. The figure consists of 726 stacked horizontal line, with each horizontal line representing a participant. In this figure, NDI category is presented at 2, 5, and 8 years of age. This figure shows overall patterns of increasing and decreasing trajectories, including patterns in missing data. The blank spaces indicate missing data for that follow-up age.