Prognostic value of diffusion-weighted magnetic resonance imaging of the fetal brain in fetal growth restriction: results of a prospective multicenter study.

OBJECTIVE: To prospectively measure the apparent diffusion coefficient (ADC) values between 28 and 32 weeks of gestation in different cerebral territories of fetuses with estimated fetal weight (EFW) ≤ 5th centile to analyse their association with an adverse perinatal outcome. METHODS: A prospective multi-center study involving 6 tertiary perinatal centres was conducted. Inclusion criteria were: (i) singleton small-for-gestational-age (SGA) fetuses with EFW ≤ 5th percentile between 28 and 32 weeks of gestation whatever the results of the umbilical Doppler and maternal uterine Doppler examinations. A fetal MRI examination with diffusion-weighted sequences (DWI) was performed within 14 days following the inclusion. ADC values were measured in frontal and occipital white matter, centrum semi-ovale, basal ganglia, cerebellar hemispheres and pons. Ultrasound examination was performed within one week prior to MRI examination. The primary outcome was a composite measure of adverse perinatal outcome defined as any of the following: perinatal death, admission to neonatal intensive care units with a mechanical ventilation > 48 hours, necrotising enterocolitis, grade III-IV intraventricular haemorrhage or periventricular leucomalacia. A univariate comparison of median ADC values in all cerebral territories between fetuses with adverse perinatal outcome and those without was performed. Association between ADC values and adverse perinatal outcome was then performed using multilevel logistic regression models to adjust for other common prognostic factors for growth-restricted fetuses. RESULTS: MRI examination was performed in 64 patients. Five patients were excluded owing to fetal movements artefacts on DWI (7.8%) and two patients were excluded for termination of pregnancies with no link to fetal growth restriction. One intra uterine death occurred secondary to severe IUGR. Among the 56 live born neonates delivered at a mean (SD) GA of 33.6 (3.0) weeks with a mean birth weight of 1441 (566) g, four neonatal deaths occurred. In addition, two neonates required prolonged mechanical ventilation, one of whom also developed necrotising enterocolitis. Finally, 7 cases out of 57 had adverse perinatal outcome (12.3%, IC 95%=[3.8-20.8%]). The ADC values in the frontal region were significantly lower in the adverse perinatal outcome group compared with the favourable outcome group (mean values of both hemispheres: 1.68 vs 1.78 10-3 mm2 /s, p=0.04). No significant difference in ADC values was observed between groups in other territories. A cut-off value of 1.70 10-3 mm2 /s was associated with a sensitivity of 57% [0.18-0.90], a specificity of 78% [0.63-0.88], a PPV of 27% [0.08-0.55] and a NPV of 93% [0.80-0.98] in predicting adverse perinatal outcome. A mean frontal ADC value < 1.70 10-3 mm2 /s was not significantly associated with an increased risk of adverse perinatal outcome either in the univariate analysis (p=0.07) nor when adjusting for GA at MRI examination and fetal sex (OR=6.06 [0.9-37.1], p=0.051) or after adjusting for umbilical artery Doppler (OR=5.27[0.75-36.9]). CONCLUSION: This first prospective multicentric cohort study of DWI in the setting of SGA fetuses reported lower ADC values in the frontal WM territory in fetuses with adverse perinatal outcome. The prognostic value of these changes needs further standardized evaluation of the neurodevelopment of the children born with growth restriction. This article is protected by copyright. All rights reserved.