Brain imaging and neurodevelopmental outcome at school age in preterm-born infants: Effects of neonatal hydrocortisone treatment

Abstract

A 2-year cohort of 236 preterm-born infants (gestational age < 32 weeks and/or birth weight < 1500 grams), born between March 1, 1991 and March 1, 1993 and admitted to the NICU of the Wilhelmina Children's Hospital, was evaluated at school age. This cohort represented 83.4% of the surviving population of this time period. A normal neonatal cranial ultrasound excluded the occurrence of major abnormalities on later MRI in 99% of cases. Those with a normal or mildly abnormal cranial ultrasound had an approximately 50% chance of being in the corresponding MRI group. Over 70% of the children with a severely abnormal cranial ultrasound had major abnormalities on later MRI. MRI findings correlated better with outcome than ultrasound, although statistically significant, these differences were clinically not relevant. The mean total cross-sectional corpus callosum (CC) area, measured at school age, was significantly smaller in preterm-born infants compared with their term-born controls The preterm children with cerebral palsy (CP) had significantly smaller mean corpus callosum areas compared with the preterms who did not develop CP. The preterms without CP also had significantly smaller body, posterior and total CC areas compared with term-born controls. There was a significant inverse association between the total impairment score (TIS) and the areas of the CC. Higher TIS (indicating poorer motor function) was strongly related to smaller total CC area. A larger CC was strongly related to better scores on the VMI test. In the second part of the thesis, the impact of neonatal hydrocortisone administration, to treat chronic lung disease in ventilator-dependent preterm-born infants, on long-term outcome was investigated. The most commonly used corticosteroid worldwide to treat these infants is dexamethasone, but the adverse side-effects on long-term development are alarming. The Wilhelmina Children's Hospital has always used the much milder steroid hydrocortisone. At a median age of 8.1 years, neurocognitive assessment included an IQ test, a Visual-Motor Integration test and a memory test (15-word recall). Motor performance was assessed with the Movement Assessment Battery for Children. A MRI of the brain was obtained and in the last 60 children, three-dimensional MRI with advanced image-processing and proton magnetic resonance spectroscopy of the hippocampus were added to the protocol. Sixty-two hydrocortisone-treated preterm-born children were compared with 164 non-treated preterm-born children. Adjustments for gestational age, birth weight, gender, mechanical ventilation and small for gestational age was made. Adjusted mean IQ, VMI and memory test results were the same in the hydrocortisone and the non-steroid group. Motor function and incidence of CP in both groups was not different. Occurrence of brain lesions on MRI was identical for the two groups. Hydrocortisone-treated children had very similar volumes of gray matter, white matter, and cerebrospinal fluid, compared with non-treated infants. The volumes and proton spectroscopy ratios of the hippocampus were not significantly different between the hydrocortisone group and the non-steroid group. There was no relation between NAA/(Cho+Cr) ratios and memory nor between NAA/(Cho+Cr) ratios and IQ. Neonatal hydrocortisone treatment for BPD had no long-term effects on neurodevelopment