Association between fetal brain diffusion-weighted imaging and postnatal neurodevelopmental outcome after prenatal...

Myelomeningocele (MMC) is associated with significant alterations of the brain microstructure, which can impair long-term neurodevelopmental outcomes. By measuring the random displacement of water molecules within the brain, magnetic resonance imaging (MRI)-based diffusion-weighted imaging (DWI) can provide objective metrics, such as apparent diffusion coefficient (ADC) values, which allow the fetal brain microstructure to be characterized. The aim of this study was to compare prenatal brain ADC values, obtained using MRI-DWI, between infants with prenatally repaired MMC who had normal vs impaired neurodevelopmental outcomes, assessed ≥ 18 months of age.

This retrospective study included children who underwent prenatal MMC repair using either a fetoscopic or open-hysterotomy surgical approach between July 2012 and June 2022, at a single tertiary hospital. A 1.5-Tesla MRI-DWI scan of the fetal brain was performed using standard departmental protocols 6 weeks after surgery. ADC values were measured in the right and left hemispheric white matter of the frontal, parietal, temporal and occipital lobes, as well as within the basal ganglia, pons, cerebellar hemispheres and vermis. Neurodevelopment was evaluated by a developmental pediatrician at or after 18 months of age, using the Capute Scales (Clinical Adaptive Test (CAT) for problem-solving skills and fine motor skills and Clinical Linguistic and Auditory Milestone Scale (CLAMS) test for language) and the gross motor domain of the Revised Gesell Developmental Schedules. The Developmental Profile-3 (DP-3) test was also conducted during parental interview at or after 18 months of age, which evaluates five qualities of development: physical, adaptive behavior, social-emotional, cognitive and communication skills. Developmental quotients were calculated as: (age equivalent on Capute Scales, gross motor or DP-3 test/age at assessment) × 100. A normal developmental quotient score was defined as ≥ 85 and a score of < 85 indicated neurodevelopmental impairment (NDI), compared with reference values. ADC values measured in each brain region were compared between children who later had a normal developmental quotient score vs those with a score < 85, using the Mann-Whitney U-test and logistic regression analysis, adjusting for the child's age at the time of neurodevelopmental testing, gestational age at the time of MRI-DWI and gestational age at delivery.

A total of 50 children were included (39 that underwent prenatal fetoscopic repair and 11 that underwent prenatal open-hysterotomy repair). A prenatal MRI-DWI scan was performed after surgery at a median of 30.9 (interquartile range (IQR), 30.5-31.4) weeks' gestation. The Capute Scales and gross motor scores were available in 31/50 (62.0%) and 29/50 (58.0%) cases, respectively, and were obtained at a median age of 23.0 (IQR, 18.0-25.5) months and 23.0 (IQR, 21.0-26.2) months, respectively. Among these cases, 22/31 (71.0%), 19/31 (61.3%) and 3/29 (10.3%) scored ≥ 85 on the CLAMS test, CAT and gross motor test, respectively. The DP-3 test score was available in 42/50 (84.0%) children and was conducted at a median age of 24.5 (IQR, 19.0-26.7) months. Among these children, 18/42 (42.9%), 28/42 (66.7%), 38/42 (90.5%), 35/42 (83.3%) and 33/42 (78.6%) had a score ≥ 85 for the physical, adaptive behavior, social-emotional, cognitive and communication domains, respectively. After adjustment, fetal ADC values obtained 6 weeks after surgery were significantly higher in all fetal brain regions studied (P < 0.05 for all), except for the vermis (P = 0.12) and pons (P = 0.05), in infants who later had a CLAMS test score indicating NDI compared to those with a score ≥ 85. Additionally, fetal ADC values were significantly higher in all fetal brain regions, except for the left temporal lobe (P = 0.05), left occipital lobe (P = 0.06), pons (P = 0.30), right and left cerebellum (P = 0.55 and 0.24, respectively) and vermis (P = 0.76), in infants who later had a CAT score indicating NDI compared to those with a normal score. Fetal ADC values were also significantly higher in the parietal and temporal lobes as well as in the pons (P < 0.05 for all) in infants who later had a DP-3 cognitive and communication score indicating NDI compared to those with a normal score. There was no difference in fetal ADC values in any of the brain regions studied between children with scores indicating normal vs impaired neurodevelopment on the gross motor test, the DP-3 physical, adaptive behavior and social-emotional domains or the DP-3 general development score.

Infants with NDI in problem-solving, cognitive and communication skills exhibited significant differences in their brain microstructure, as demonstrated by higher ADC values measured in utero 6 weeks after prenatal MMC repair, compared to those with normal neurodevelopmental outcomes as assessed at or after 18 months of age. These findings have significant clinical implications, especially for the early identification and management of children at risk for NDI after prenatal MMC repair. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.