Born Near the Limit of Viability – Developmental Outcomes 2.5 Years Later

Abstract: Although advances in neonatal care have resulted in increased survival rates among extremely preterm infants (born < 28 gestational weeks), they still face substantial morbidity risks during the neonatal period. The question of possible later outcomes is a key issue faced by health care professionals working with these infants. Objectives The objective of the present thesis was to explore developmental outcomes of extremely preterm birth at corrected age 2.5 years. The included studies contribute to the general objective differently: Study I examines developmental differences between children born extremely preterm and full term, and prevalence of mild, moderate or severe developmental delay. Study II investigates developmental function differences between boys and girls born extremely preterm, and sex-specific predictors of functioning outcome. Study III examines the extent of behavioral problems in children born extremely preterm, and the relationships between extremely preterm birth, development, and behavioral problems. Methods As a part of the population-based Extremely Preterm Infants in Sweden Study (EXPRESS), 399 children born before 27 weeks of gestation and 366 control children born at term were assessed with the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), assigning scores for cognition, communication, and motor functions. Based on control group mean scores, prevalences of developmental delay in the preterm group were calculated (Study I). Sex-group differences in Bayley-III scores were calculated. Socioeconomic, birth, and neonatal factors were used in models calculated separately for boys and girls born extremely preterm, to determine sex-specific predictors of developmental outcome (Study II). The Child Behavior Checklist for the ages 1½–5 years (CBCL/1½–5) was used to obtain standardized parental ratings of children’s behavioral functioning, assigning composite scores for internalizing, externalizing behavior and total problems. Group differences in behavioral difficulties and prevalence of clinical problems were calculated. Results Analyses showed significantly lower performances of the preterm group compared with the control group on the Bayley-III subtests. Prevalence of moderate-severe delay was 10.8% in cognitive, 11.8% in receptive communication, 14.5% in expressive communication, 12.4% in fine motor, and 7.0% in gross motor functions (Study I). Girls scored significantly higher than boys on all Bayley-III indices. In both sexes, brain injury, long-term ventilator treatment, and foreign-born mother predicted lower scores. Having breast milk by hospital discharge predicted higher scores. Severe retinopathy of prematurity was the strongest predictor of cognitive and language deficits in boys. For girls, high parental education predicted higher cognitive and language scores, whereas severe bronchopulmonary dysplasia was the strongest predictor of motor deficits (Study II). Preterm children had significantly higher mean T-scores on CBCL/1½–5 internalizing, externalizing and total problems, as compared with the controls, but these were still within average range. The proportion of subjects showing behavioral problems within the clinical range was significantly higher in the preterm group. Levels of cognitive, language and motor development mediated the between-group differences in behavioral problems. Conclusions Extremely preterm children show significantly lower cognitive, communicative and motor function levels at 2.5 years compared with children born at term. Extreme prematurity seems to affect boys more than girls. Socioeconomic and neonatal factors confer similar risks or protections to both sexes, but some variables pose certain risks for boys and some other for girls. Our findings encourage behavioral assessments during preschool years and emphasize the importance of considering multifactorial pathways of prediction when examining prematurity outcome.