Abstract

OBJECTIVES: the MOMS randomized trial has demonstrated that prenatal spina bifida aperta (SBA) repair via open approach is safe and effective for both mother and fetus, yet half of the infants have incomplete reversal of hindbrain herniation and no improvement in neuromotor function. One contributing factor may be the incompleteness of the neurosurgical repair causing persistent in utero leakage of cerebrospinal fluid (CSF) and exposure of the spinal cord to the amniotic fluid until birth. We aim to investigate the neurostructural and neurofunctional efficacy of the watertightness of prenatal SBA repair.

METHODS: a superiority study was conducted in the validated SBA fetal lamb model and powered (n=7 per group). Outcomes of lambs undergoing watertight or non-watertight multilayer repairs through an open approach were compared to those in unrepaired SBA lambs at delivery (term=145 days). At ~75-day fetal lambs underwent standardized induction of lumbar SBA. At ~100 days, they were assigned to one of the three groups and subsequently to either watertight or non-watertight layered repair group based on an intraoperative watertightness test using subcutaneous fluoresceine injection. Finally, at 1-2 postnatal days, we assessed reversal of hindbrain herniation on Magnetic Resonance Imaging (MRI) as primary outcome. Secondary proxies of neuroprotection were CSF leakage at the repair site; hindlimb motor function based on joint movement score, locomotor grade and Motor Evoked Potentials (MEP); neuroprotection score encompassing live birth, hindbrain herniation reversal, absent CSF leakage and joint score ≥9/15; and brain and spinal cord histology and immunohistochemistry. As the watertightness test is not clinically usable, we developed a potential surrogate intraoperative quality score and assessed its relationship with improved outcomes. This four-point scoring system is based on visual assessment of the quality of the skin repair (suture inter-run distance ≤3mm, absence of tear and ischemia).

RESULTS: Compared to unrepaired lambs, watertight repair was neuroprotective in 5/7 lambs (neuroprotection score of 4/4), as evidenced by a 100% reversal of hindbrain herniation on MRI; lower CSF leakage rate (14%); better hindlimb motor function evidenced by higher joint movement score, locomotor grade, and MEP area-under-the-curve and peak-to-peak amplitude; higher neuronal density in the hippocampus and corpus callosum; and higher reactive astrogliosis at the SBA lesion epicenter. Conversely, non-watertight SBA repair did not achieve the same level of neuroprotection (1/7) due to non-significant 86% hindbrain herniation reversal, no motor function improvement, high CSF leakage (43%), low brain neuron count in both regions and low spinal astroglial cell area at the epicenter. Like watertight layered repair, a high quality score (≥2/3) was associated with improved outcomes yet watertightness test and quality score could not be used interchangeably due to results discrepancies.

CONCLUSIONS: A watertight layered fetal SBA repair improves brain and spinal cord structure and function in the fetal lamb model. This translational research has important clinical implication and neurosurgical technique that achieves watertightness should be adopted in all fetal centers to improve neuroprotection. Future clinical studies could assess whether the high quality of the repair correlates with clinical outcomes for neuroprotection. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology
Early online date30 Mar 2022
DOIs
Publication statusE-pub ahead of print - 30 Mar 2022

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