The differential associative relationship between early risk factors, neonatal morbidities and early neurodevelopmental outcome in preterm infants <29 weeks' gestation.

Background: Very preterm infants of <29 weeks' gestation are at high risk for adverse neurodevelopment due to multiple risk factors in the early stages of life. There is little information regarding the associative effects of risk factors in early life, neonatal morbidities and subsequent neurodevelopmental outcomes.

Aims: Investigate the association of early neurodevelopmental outcomes, neonatal complications and the risk factors in the early hours of life in a cohort of preterm infants <29 weeks' gestational age.

Methods: We enrolled all surviving preterm neonates born at gestation <29 weeks between January 2015 and June 2021 in the University of Hong Kong-Shenzhen Hospital. Demographic and clinical characteristics were collected from a database of the neonatal intensive care unit. Neurodevelopmental outcomes of the survivors were evaluated using the Ages and Stages Questionnaire (ASQ-3) which were measured at the adjusted age of 12 to 18 months. The multivariate linear regression model was used to determine correlation presented as β coefficient (β) with 95 % confidence intervals (CI).

Results: In this cohort of 56 survivors <29 weeks' gestation, urine output within the first 12 h of life and Apgar score at 5 min were positively associated with different domains of ASQ-3 score, however male sex and highest fraction of inspired oxygen (FiO) in the first 12 h of life were negatively related with at least one of neurocognitive domains of ASQ-3 at adjusted age of 12 to 18 months. During hospitalization, in addition to the frequency of packed red cell transfusions, the development of severe necrotizing enterocolitis was inversely associated with both neuromotor and neurocognitive skills (gross motor domain: β = -16.93, CI: -32.04, -1.82; fine motor domain: β = -16.42, CI: -28.82, -4.02; problem solving domain: β = -13.14, CI: -24.45, -1.83; all P < 0.05), whereas severe intraventricular hemorrhage had adverse effects on gross motor only (β = -13.04, CI: -24.42, -1.65; P = 0.03). Bronchopulmonary dysplasia and retinopathy of prematurity were not related with ASQ-3.

Conclusions: In this small cohort study of very preterm neonates born at <29 weeks' gestation, risk factors in the early hours of life and neonatal morbidities during hospitalization had differential associative relationships with ASQ-3 at 12-18 months adjusted age. This information may be important for parental counseling and management including early diagnosis and intervention.