Comparison of brain microstructure after prenatal spina bifida repair by either laparotomy-assisted fetoscopic or open approach.

OBJECTIVE: To compare prenatal and postnatal brain microstructure between infants that underwent fetoscopic myelomeningocele (MMC) repair and those that had open-hysterotomy repair. METHODS: This was a longitudinal retrospective cohort study of 57 fetuses that met the Management of Myelomeningocele Study (MOMS) trial criteria and underwent prenatal MMC repair, by a fetoscopic (n = 27) or open-hysterotomy (n = 30) approach, at 21.4-25.9 weeks' gestation. Fetoscopic repair was performed under CO2 insufflation, according to our protocol. Diffusion-weighted magnetic resonance imaging (MRI) was performed before surgery in 30 cases (14 fetoscopic and 16 open), at 6 weeks postsurgery in 48 cases (24 fetoscopic and 24 open) and within the first year after birth in 23 infants (five fetoscopic and 18 open). Apparent diffusion coefficient (ADC) values from the basal ganglia, frontal, occipital and parietal lobes, mesencephalon and genu as well as splenium of the corpus callosum were calculated. ADC values at each of the three timepoints (presurgery, 6 weeks postsurgery and postnatally) and the percentage change in the ADC values between the timepoints were compared between the fetoscopic-repair and open-repair groups. ADC values at 6 weeks after surgery in the two prenatally repaired groups were compared with those in a control group of eight healthy fetuses that underwent MRI at a similar gestational age (GA). Comparison of ADC values was performed using the Student's t-test for independent samples (or Mann-Whitney U-test if non-normally distributed) and multivariate general linear model analysis, adjusting for GA or age at MRI and mean ventricular width. RESULTS: There were no differences in GA at surgery or GA/postnatal age at MRI between the groups. No significant differences were observed in ADC values in any of the brain areas assessed between the open-repair and fetoscopic-repair groups at 6 weeks after surgery and in the first year after birth. No differences were detected in the ADC values of the studied areas between the control and prenatally repaired groups, except for significantly increased ADC values in the genu of the corpus callosum in the open-hysterotomy and fetoscopic-repair groups. Additionally, there were no differences between the two prenatally repaired groups in the percentage change in ADC values at any of the time intervals analyzed. CONCLUSIONS: Fetoscopic MMC repair has no detectable effect on brain microstructure when compared to babies repaired using an open-hysterotomy technique. CO2 insufflation of the uterine cavity during fetoscopy does not seem to have any isolated deleterious effects on fetal brain microstructure. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal brain imaging for predicting need for postnatal hydrocephalus treatment in fetuses that had neural tube defect repair in utero.

OBJECTIVE: To determine if brain imaging in fetuses that underwent prenatal repair of neural tube defect (NTD) can predict the need for postnatal hydrocephalus treatment (HT) in the first year postpartum. METHODS: This was a retrospective study of fetuses diagnosed with open NTD that had in-utero myelomeningocele repair between April 2014 and April 2016. Independent variables were collected from four chronological sets of fetal images: presurgery ultrasound, presurgery magnetic resonance imaging (MRI), 6-week postsurgery MRI and predelivery ultrasound. The following independent variables were collected from all image sets unless otherwise noted: gestational age, head circumference, mean ventricular width, ventricular volume (MRI only), hindbrain herniation (HBH) score (MRI only), and level of lesion (LOL), defined as the upper bony spinal defect (presurgery ultrasound only). Based on these measurements, additional variables were defined and calculated including change in degree of HBH, ventricular width growth (mm/week) and ventricular volume growth (mL/week). The need for HT (by either ventriculoperitoneal shunt or endoscopic third ventriculostomy with choroid plexus cauterization) was determined by a pediatric neurosurgeon using clinical and radiographic criteria; a secondary analysis was performed using the MOMS trial criteria for hydrocephalus. The predictive value of each parameter was assessed by receiver-operating characteristics curve and logistic regression analyses. RESULTS: Fifty affected fetuses were included in the study, of which 32 underwent open hysterotomy and 18 fetoscopic repair. Two neonates from the open hysterotomy group died and were excluded from the analysis. The mean gestational ages for the presurgery ultrasound, presurgery MRI, postsurgery MRI and predelivery ultrasound were 21.8 ± 2.1, 22.0 ± 1.8, 30.4 ± 1.6 and 31.0 ± 4.9 weeks, respectively. A total of 16 subjects required HT. The area under the curve (AUC) of predictive accuracy for HT showed that HBH grading on postsurgery MRI had the strongest predictive value (0.86; P < 0.01), outperforming other predictors such as postsurgery MRI ventricular volume (0.73; P = 0.03), MRI ventricular volume growth (0.79; P = 0.01), change in HBH (0.82; P = 0.01), and mean ventricular width on predelivery ultrasound (0.73; P = 0.01). Other variables, such as LOL, mean ventricular width on presurgery ultrasound, mean ventricular width on presurgery and postsurgery MRI, and ventricular growth assessment by MRI or ultrasound, had AUCs < 0.7. Optimal cut-offs of the variables with the highest AUC were evaluated to improve prediction. A combination of ventricular volume growth ≥ 2.02 mL/week and/or HBH of 3 on postsurgery MRI were the optimal cut-offs for the best prediction (odds ratio (OR), 42 (95% CI, 4-431); accuracy, 84%). Logistic regression analyses showed that persistence of severe HBH 6 weeks after surgery by MRI is one of the best predictors for HT (OR, 39 (95% CI, 4-369); accuracy, 84%). There was no significant change in the results when the MOMS trial criteria for hydrocephalus were used as the dependent variable. CONCLUSIONS: Persistence of HBH on MRI 6 weeks after prenatal NTD repair independently predicted the need for postnatal HT better than any ultrasound- or other MRI-derived measurements of ventricular characteristics. These results should aid in prenatal counseling and add support to the hypothesis that HBH is a significant driver of hydrocephalus in myelomeningocele patients. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Imágenes cerebrales prenatales para predecir el tratamiento postnatal de la hidrocefalia en fetos con reparación de defectos del tubo neural OBJETIVOS: Determinar si las imágenes cerebrales en fetos que se sometieron a reparación prenatal de defectos del tubo neural (DTN) pueden predecir la necesidad de tratamiento postnatal de la hidrocefalia (TH) en el primer año después del parto. MÉTODOS: Este fue un estudio retrospectivo de fetos diagnosticados con DTN aun abierto cuyo mielomeningocele fue reparado en el útero, entre abril de 2014 y abril de 2016. Se recolectaron variables independientes de cuatro conjuntos cronológicos de imágenes fetales: ecografía prequirúrgica, imágenes por resonancia magnética (IRM) prequirúrgica, imágenes por resonancia magnética (IRM) posquirúrgica a las seis semanas y ecografía previa al parto. Las siguientes variables independientes se recolectaron de todos los conjuntos de imágenes, a menos que se indique lo contrario: edad gestacional, perímetro cefálico, ancho ventricular medio, volumen ventricular (IRM solamente), puntaje de hernia del rombencéfalo (HR) (IRM solamente) y nivel de lesión (NDL), definido como el defecto espinal óseo superior (ecografía prequirúrgica solamente). A partir de estas mediciones se definieron y calcularon variables adicionales, como el cambio en el grado de HR, el aumento del ancho ventricular (mm/semana) y el aumento del volumen ventricular (mL/semana). La necesidad de TH (ya sea por derivación ventriculoperitoneal o por ventriculostomía endoscópica del tercer ventrículo y cauterización del plexo coroideo) fue determinada por un neurocirujano pediátrico utilizando criterios clínicos y radiográficos; se realizó un análisis secundario utilizando los criterios del estudio MOMS para la hidrocefalia. El valor predictivo de cada parámetro se evaluó mediante un análisis de la curva de la característica operativa del receptor y de la regresión logística. RESULTADOS: Se incluyeron en el estudio 50 fetos afectados, de los cuales 32 se sometieron a histerotomía abierta y 18 a reparación fetoscópica. Dos de los recién nacidos del grupo de histerotomía abierta murieron y fueron excluidos del análisis. Las edades gestacionales medias para la ecografía prequirúrgica, la IRM prequirúrgica, la IRM postoperatoria y la ecografía previa al parto fueron 21,8 ±2,1; 22,0 ±1,8; 30,4 ±1,6 y 31,0 ±4,9 semanas, respectivamente. Un total de 16 sujetos requirieron TH. El área bajo la curva (ABC) de precisión predictiva para la TH mostró que la clasificación de la HR en la IRM postoperatoria tuvo el valor predictivo más fuerte (0,86; P<0.01), por encima de otros valores predictivos como el volumen ventricular en la IRM posquirúrgica (0,73; P=0,03), el crecimiento del volumen ventricular en la IRM (0,79; P=0,01), cambios en la HR (0,82; P=0,01), y el ancho ventricular medio en la ecografía previa al parto (0,73; P=0,01). Otras variables, como el NDL, la anchura ventricular media en la ecografía prequirúrgica, la anchura ventricular media en la IRM prequirúrgica y posquirúrgica, y la evaluación del crecimiento ventricular mediante ecografía o IRM, tuvieron AUC <0,7. Para mejorar la predicción se evaluaron los límites óptimos de las variables con las AUC más altas. Los límites óptimos para la mejor predicción (razones de momios [RM], 42 [IC 95%: 4-431]; precisión, 84%) fueron una combinación de crecimiento del volumen ventricular ≥2,02 mL/semana y/o HR de 3 en la IRM postoperatoria. Los análisis de regresión logística mostraron que la persistencia de la HR grave a las 6 semanas después de la cirugía en IRM es uno de los mejores predictores de la TH (RM, 39 (IC 95%: 4-369); precisión, 84%). Los resultados no cambiaron de forma significativa cuando se utilizaron los criterios del estudio MOMS para la hidrocefalia como variable dependiente. CONCLUSIONES: La persistencia de la HR en la IRM 6 semanas después de la reparación prenatal de DTN predijo independientemente la necesidad de la TH postnatal mejor que cualquier ecografía o que otras mediciones de las características ventriculares a partir de IRM. Estos resultados deberían ayudar en el asesoramiento previo al parto y a apoyar la hipótesis de que la HR es un impulsor significativo de la hidrocefalia en pacientes con mielomeningocele.