Invasive Procedures in Preterm Children: Brain and Cognitive Development at School Age

TLDR

Very preterm infants undergo many invasive procedures, and higher numbers of such procedures have been linked to abnormal brain development in both animal models and human neonates, even after accounting for other clinical risks. This study examined whether the number of invasive procedures during neonatal care predicts long‑term alterations in white‑matter microstructure and cognitive outcomes at school age in children born very preterm. Fifty very‑preterm children underwent MRI (T1/T2 and diffusion tensor imaging for fractional anisotropy in seven white‑matter regions) and Wechsler Intelligence Scale for Children‑IV testing at a median age of 7.6 years, and multivariate models adjusted for clinical confounders were used to relate procedure counts to brain and cognitive measures. Higher counts of invasive procedures were associated with lower fractional anisotropy and, through an interaction with white‑matter integrity, with lower IQ, indicating that neonatal invasive procedures contribute to long‑term white‑matter abnormalities and reduced cognitive performance.

Abstract

Very preterm infants (born 24-32 weeks' gestation) undergo numerous invasive procedures during neonatal care. Repeated skin-breaking procedures in rodents cause neuronal cell death, and in human preterm neonates higher numbers of invasive procedures from birth to term-equivalent age are associated with abnormal brain development, even after controlling for other clinical risk factors. It is unknown whether higher numbers of invasive procedures are associated with long-term alterations in brain microstructure and cognitive outcome at school age in children born very preterm.Fifty children born very preterm underwent MRI and cognitive testing at median age 7.6 years (interquartile range, 7.5-7.7). T1- and T2-weighted images were assessed for the severity of brain injury. Magnetic resonance diffusion tensor sequences were used to measure fractional anisotropy (FA), an index of white matter (WM) maturation, from 7 anatomically defined WM regions. Child cognition was assessed using the Wechsler Intelligence Scale for Children-IV. Multivariate modeling was used to examine relationships between invasive procedures, brain microstructure, and cognition, adjusting for clinical confounders (eg, infection, ventilation, brain injury).Greater numbers of invasive procedures were associated with lower FA values of the WM at age 7 years (P = .01). The interaction between the number of procedures and FA was associated with IQ (P = .02), such that greater numbers of invasive procedures and lower FA of the superior WM were related to lower IQ.Invasive procedures during neonatal care contribute to long-term abnormalities in WM microstructure and lower IQ.