Neuroprotection is improved by watertightness of fetal spina bifida repair in the sheep model

Joyeux, Luc; Merwe, Johannes van der; Aertsen, Michaël; Patel, Premal A.; Khatoun, Ahmad; Cunha, Marina Gabriela Monteiro Carvalho Mori da; Vleeschauwer, Stéphanie De; Parra, Johanna; Danzer, Enrico; McLaughlin, M; Stoyanov, Danail; Vercauteren, Tom; Ourselin, Sébastien; Radælli, Enrico; Coppi, Paolo De; Calenbergh, Frank Van; Deprest, Jan

doi:10.1002/uog.24907

Cited by 10 publications

(24 citation statements)

References 63 publications

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“…We also evaluated the white matter in our fetal surgery population, and, again, no differences in volume or shape were found compared to normal controls [ 26 ]. These fetuses however had a variable degree of ventriculomegaly prior to fetal surgery; after the operation, the ventricular width continued to increase, in concordance with the observations of others [ 8 12 16 26 ]. To us, it remains unclear how the white matter volume evolves during the remainder of the pregnancy and in postnatal life in this subset of patients.…”

Section: Fetal Brain Mri In Spina Bifida Apertasupporting

confidence: 89%

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The Role of Fetal Brain Magnetic Resonance Imaging in Current Fetal Medicine

Aertsen

2022

Journal of the Belgian Society of Radiology

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In open spina bifida we studied the use of MRI for the assessment of the posterior fossa and prevalence of supratentorial anomalies before and after in utero repair. New postprocessing techniques were applied to evaluate fetal brain development in this population compared to controls. In fetuses with congenital diaphragmatic hernia, we evaluated the brain development in comparison to controls. Diffusion weighted imaging was applied to study difference between fetuses with proven first trimester cytomegalovirus infection and controls. Finally, we investigated the value of third trimester fetal brain MRI after treatment for complicated monochorionic diamniotic pregnancies.

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Section: Fetal Brain Mri In Spina Bifida Apertasupporting

confidence: 89%

“…Earlier studies, such as the one from Sutton [ 11 ]), also reported such changes between three and six weeks after the surgery in all fetuses where this was measured. The re-accumulation of intracranial CSF can be an interesting proxy of the efficacy of spinal closure [ 12 ].…”

Section: Fetal Brain Mri In Spina Bifida Apertamentioning

confidence: 99%

The Role of Fetal Brain Magnetic Resonance Imaging in Current Fetal Medicine

Aertsen

2022

Journal of the Belgian Society of Radiology

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“…This technique is used clinically for fetoscopic repair with the purpose of arresting CSF leakage. 14,32,33 The multi-layered closure included dural coverage with dural patch followed by skin approximation but without myofascial or paraspinal muscle closure-which is not possible in this model. The experiment was not designed to compare different neurosurgical techniques but to determine the difference in local host response to different dural patches.…”

Section: Discussionmentioning

confidence: 99%

“…We excluded animals that displayed any signs of insufficient or non-watertight closure as unsuccessful closure may be less neuroprotective. 14 The experiment was neither powered to study the spectrum of effects of incomplete SBA closure. Data from incomplete closure were not considered for analysis as experiments in large animal models demonstrate that ongoing leakage is associated with deterioration of hindlimb motor function, hence it is likely to be less neuroprotective.…”

Section: Discussionmentioning

confidence: 99%

“…7 In comparison, most fetoscopic techniques insert a dural patch over the spinal cord, to simplify the techniques and to achieve a watertight repair. 14 To our knowledge, there is only one biocellulose patch which was experimentally tested for fetal SBA repair in a fetal rabbit model (Biofill ® , Fibrocel). 15,16 Other more widely available dural patches used in adult neurosurgery, such as the DuraGen ® Plus TM (Integra) and Durepair TM Regeneration Matrix (Medtronic), have not been formally tested for fetal surgery, although they are already used clinically.…”

Section: Introductionmentioning

confidence: 99%

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Local host response of commercially available dural patches for fetal repair of spina bifida aperta in rabbit model

et al. 2023

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Objective Fetal surgery for spina bifida aperta (SBA) by open hysterotomy typically repairs anatomical native tissue in layers. Increasingly, fetoscopic repair is performed using a dural patch followed by skin closure. We studied the host response to selected commercially available patches currently being used in a fetal rabbit model for spina bifida repair. Methods SBA was surgically induced at 23–24 days of gestation (term = 31 days). Fetal rabbits were assigned to unrepaired (SBA group), or immediate repair with Duragen™ or Durepair™. Non‐operated littermates served as normal controls. At term, spinal cords underwent immunohistochemical staining including Nissl and glial fibrillary acidic protein. We hypothesized that spinal cord coverage with a dural patch and skin closure would preserve motor neuron density within the non‐inferiority limit of 201.65 cells/mm2 and reduce inflammation compared to unrepaired SBA fetuses. Results Motor neuron density assessed by Nissl staining was conserved both by Duragen (n = 6, 89.5; 95% CI −158.3 to −20.6) and Durepair (n = 6, 37.0; 95% CI −132.6 to −58.5), whereas density of GFAP‐positive cells to quantify inflammation was lower than in unrepaired SBA‐fetuses (SBA 2366.0 ± 669.7 cells/mm2 vs. Duragen 1274.0 ± 157.2 cells/mm2; p = 0.0002, Durepair 1069.0 ± 270.7 cells/mm2; p < 0.0001). Conclusions Covering the rabbit spinal cord with either Duragen or Durepair followed by skin closure preserves motor neuron density and reduces the inflammatory response.

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Length of hysterotomy for fetal spina bifida repair is associated with prematurity risk

Watananirun,

Vargas,

Vergote

et al. 2024

Prenatal Diagnosis

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ObjectiveTo investigate whether prenatal repair of spina bifida aperta through mini‐hysterotomy results in less prematurity, as compared to standard hysterotomy, when adjusting for known prematurity risks.MethodsWe performed a bi‐centric, propensity score matched, controlled study, that is, adjusting for factors earlier reported to result in premature delivery or membrane rupture, in consecutive women having prenatal repair either through stapled hysterotomy or sutured mini‐hysterotomy (≤3.5 cm). Matches were pairwise compared and cox‐regression analysis was performed to define the hazard ratio of delivery <37 weeks.ResultsOf 346 meeting the MOMS‐criteria, 78 comparable pairs were available for matched‐controlled analysis. Mini‐hysterotomy patients were younger and had a higher BMI. Mini‐hysterotomy was associated with a 1.67‐lower risk of delivery <37 weeks (hazard ratio: 0.60; 95% CI: 0.42–0.85; p = 0.004) and 1.72 for delivery <34 + 6 weeks (hazard ratio: 0.58; 95% CI: 0.34–0.97; p = 0.037). The rate of intact uterine scar at birth (mini‐hysterotomy: 98.7% vs. hysterotomy: 90.4%; p = 0.070), the rate of reversal of hindbrain herniation within 1 week after surgery (88.9% vs. 97.4%; p = 0.180) and the rate of cerebrospinal fluid leakage (0% vs. 2.7%; p = 0.50) were comparable.ConclusionPrenatal spina bidifa repair through mini‐hysterotomy was associated with a later gestational age at delivery and a comparable intact uterus rate without apparent compromise in neuroprotection.

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Neuroprotection is improved by watertightness of fetal spina bifida repair in the sheep model

Cited by 10 publications

References 63 publications

The Role of Fetal Brain Magnetic Resonance Imaging in Current Fetal Medicine

The Role of Fetal Brain Magnetic Resonance Imaging in Current Fetal Medicine

Local host response of commercially available dural patches for fetal repair of spina bifida aperta in rabbit model

Length of hysterotomy for fetal spina bifida repair is associated with prematurity risk

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