Perinatal factors contributing to intellectual impairment in a cohort of Japanese children with very low birth weight.

BACKGROUND To determine whether prematurity, intrauterine growth restriction (IUGR), or neonatal stress affects intellectual impairment in children with very low birth weight (VLBW). METHODS This national historical cohort study evaluated children with VLBW cared for in perinatal medical centers throughout Japan. Factors assessed included three latent variables (prematurity, IUGR, and stress during the neonatal period) and eight observed variables during perinatal period. The primary endpoint was intellectual or developmental quotient (IQ/DQ) at age ≥3 years. Structural equation model (SEM) was used to examine factors associated with IQ/DQ. RESULTS The study included 248 VLBW children, who were of mean age 5.7±2.0 years and mean IQ/DQ of 85.5 at last encounter. SEM showed that stress during the neonatal period (β=-0.37) contributed more to IQ/DQ than intrauterine malnutrition (β=0.25) and prematurity (β=0.15) and that the duration of mechanical ventilation was an important contributor to stress during the neonatal period. CONCLUSIONS Neonatal stress was more harmful to future intellectual impairment of VLBW neonates, with IUGR contributing more than prematurity. Duration of mechanical ventilation was an important risk factor in neonatal stress. Neonatologists should minimize neonatal stress in VLBW neonates, and obstetricians should monitor fetal growth restriction to prevent intellectual impairment in later life.