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We aimed to investigate the neurostructural and neurofunctional efficacy of watertight prenatal SBA repair  in a validated SBA fetal lamb model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A well\u2010powered superiority study was conducted in the validated SBA fetal lamb model (<jats:italic>n<\/jats:italic>\u2009=\u20097 per group). The outcomes of lambs which underwent watertight or non\u2010watertight multilayer repair through an open approach were compared to those of unrepaired SBA lambs (historical controls) at delivery (term\u2009=\u2009145\u2009days). At \u223c75\u2009days, fetal lambs underwent standardized induction of lumbar SBA. At \u223c100\u2009days, they were assigned to an either watertight or non\u2010watertight layered repair group based on an intraoperative watertightness test using subcutaneous fluorescein injection. At 1\u20132\u2009days postnatally, as primary outcome, we assessed reversal of hindbrain herniation using magnetic resonance imaging (MRI). Secondary proxies of neuroprotection were: absence of CSF leakage at the repair site; hindlimb motor function based on joint\u2010movement score, locomotor grade and Motor Evoked Potential (MEP); four\u2010score neuroprotection scale, encompassing live birth, complete hindbrain herniation reversal, absence of CSF leakage and joint\u2010movement score \u2265\u20099\/15; and brain and spinal cord histology and immunohistochemistry. As the watertightness test cannot be used clinically due to its invasiveness, we developed a potential surrogate intraoperative three\u2010score skin\u2010repair\u2010quality scale based on visual assessment of the quality of the skin repair (suture inter\u2010run distance \u2264\u20093\u2009mm, absence of tear and absence of ischemia), with high quality defined by a score \u2265\u20092\/3 and low quality by a score &lt;\u20092\/3, and assessed its relationship with improved outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with unrepaired lambs, lambs with watertight repair achieved a high level of neuroprotection (neuroprotection score of 4\/4 in 5\/7 <jats:italic>vs<\/jats:italic> 0\/7 lambs) as evidenced by: a significant 100% (<jats:italic>vs<\/jats:italic> 14%) reversal of hindbrain herniation on MRI; low CSF leakage (14% <jats:italic>vs<\/jats:italic> 100%); better hindlimb motor function, with higher joint\u2010movement score, locomotor grade and MEP area under the curve and peak\u2010to\u2010peak amplitude; higher neuronal density in the hippocampus and corpus callosum; and higher reactive astrogliosis at the SBA lesion epicenter. Conversely, lambs with non\u2010watertight SBA repair did not achieve the same level of neuroprotection (score of 4\/4 in 1\/7 lambs) compared with unrepaired lambs, with: a non\u2010significant 86% <jats:italic>(vs<\/jats:italic> 14%) reversal of hindbrain herniation; high CSF leakage (43% <jats:italic>vs<\/jats:italic> 100%); no improvement in motor function; low brain neuron count in both the hippocampus and corpus callosum; and small spinal astroglial cell area at the epicenter. Both watertight layered repair and high (\u2265\u20092\/3) intraoperative skin\u2010repair\u2010quality score were associated with improved outcome, but the watertightness test and skin\u2010repair\u2010quality scale could not be used interchangeably due to result discrepancies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Watertight layered fetal SBA repair is neuroprotective since it improves brain and spinal\u2010cord structure and function in the fetal lamb model. This translational research has important clinical implications. A neurosurgical technique that achieves watertightness should be adopted in all fetal centers to improve neuroprotection. Future clinical studies could assess whether a high skin\u2010repair\u2010quality score (\u2265\u20092\/3) correlates with neuroprotection. \u00a9 2022 International Society of Ultrasound in Obstetrics and Gynecology.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.24907","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T16:59:52Z","timestamp":1648659592000},"page":"81-92","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Neuroprotection is improved by watertightness of fetal spina bifida repair in the sheep model"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7331-6354","authenticated-orcid":false,"given":"L.","family":"Joyeux","sequence":"first","affiliation":[{"name":"My FetUZ Fetal Research Center, Department of Development and Regeneration Biomedical Sciences, KU Leuven  Leuven Belgium"},{"name":"Center for Surgical Technologies, Faculty of Medicine, KU Leuven  Leuven Belgium"},{"name":"Department of Obstetrics and Gynecology, Division of Woman and Child Fetal Medicine Unit, University Hospitals Leuven  Leuven Belgium"},{"name":"Department of Pediatric Surgery Texas Children's Hospital and Baylor College of Medicine  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"van der Merwe","sequence":"additional","affiliation":[{"name":"My FetUZ Fetal Research Center, Department of Development and Regeneration Biomedical Sciences, KU Leuven  Leuven Belgium"},{"name":"Center for Surgical Technologies, Faculty of Medicine, KU Leuven  Leuven Belgium"},{"name":"Department of Obstetrics and Gynecology, Division of Woman and Child Fetal Medicine Unit, University Hospitals Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1994-5365","authenticated-orcid":false,"given":"M.","family":"Aertsen","sequence":"additional","affiliation":[{"name":"Department of Radiology University Hospitals Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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