European Journal of Obstetrics & Gynecology and Reproductive Biology
Inert patch with bioadhesive for gentle foetal surgery of myelomeningocele in a sheep model☆
Introduction
Myelomeningocele (MMC) is a congenital malformation characterized by a closure defect at the posterior aspect of the spinal column that can result in considerable disability at birth and is a challenge for foetal repair [1].
The unprotected foetal neural tissue undergoes progressive damage with advancing gestational age, probably due to chemical and mechanical factors related to exposure to the uterine environment [2], [3]. In addition, a foetus with MMC usually develops Chiari II malformation of the brain, thought to be produced by the pressure disturbances resulting from a continuous loss of cerebrospinal fluid (CSF) through the defect [4].
The neurological consequences at birth are irreversible and sometimes devastating. Depending on the level and size of the defect, these may include paraplegia, sphincter incontinence, hydrocephalus, cranial nerve disturbances, respiratory problems, and death [5], [6].
The malformation is usually detected by ultrasound study between 16 and 20 weeks of gestation. The current management options for the condition include interruption of pregnancy, surgical repair following birth, birth advancement [7], and reparative foetal surgery [8].
Experimental animal studies have shown that repair of the neural tube closure defect during foetal life results in less severe hindbrain herniation [9], [10] and spinal cord injury [2], [11], [12] at birth. Nonetheless, foetal repair of MMC in humans is a challenging procedure that is not free of complications [8], [13]. Currently, this surgery is only performed in selected patients in a few centres worldwide, and the main reparative method used is open surgery by laparotomy and hysterotomy [14]. The foetal neural tube defect is usually closed in a multilayer fashion, the neural placode is dissected free, the dura is closed over the neural elements, and the skin borders are brought together and sutured [8], [15]. To achieve complete tension-free closure, it is sometimes necessary to extensively undermine the skin, perform bilateral vertically oriented incisions parallel to the defect, or add some type of sutured patch [13], [14]. These surgical manoeuvres further lengthen the operating time and may be complex because of the small surgical field, especially in large defects, in sacral areas because the skin is dissected with difficulty, and in early repair when the foetal tissue lacks the integrity required for extensive dissection and suture. Multilayer closure has also been reported in fetoscopic repair, but the method is even more technically demanding and time-consuming [13], [14], [16].
The rationale of our study was to investigate a closure method for MMC that is fast, simple, and does not require manipulation of fragile foetal tissues. Thus, the aim of this study was to assess whether a simple coverage technique using inert material and surgical sealant avoids foetal tissue manipulation, provides adequate closure of the neural tube defect, and prevents Chiari malformation.
Section snippets
Materials and method
This is an experimental study performed in healthy, 1-year-old pregnant sheep (Ripollese breed), following the National Institutes of Health Guidelines for the use of laboratory animals and with the approval of the local Ethics Committee for experimental animal use. All animals were obtained from the same provider. The procedures were carried out between January 2006 and December 2007.
Survival and surgeries
Twenty pregnant sheep were required. One ewe lost the foetus before the procedures and 8 presented twin gestations (4 UT group, 3 SI group, 1 SM group); in these cases, surgery was performed only on 1 foetus. Fifteen animals born at term (5 in each group) were ultimately available for clinical and histological analysis (79% survival) (Fig. 1).
The mean operating time for the foetal procedure (patch placement and surgical sealant) was 7.1 (SD = 1.6) min.
Clinical study
None of the animals in the UT group were able
Comment
In this experimental study of MMC in sheep, a simplified coverage technique using a sealed patch avoided foetal tissue manipulation, provided good closure of the defect, and averted secondary neural injury and Chiari malformation. The method was very fast, minimally invasive for the foetus, and resulted in regeneration of several soft tissue layers.
The multilayer tissue closure completely isolated and protected the spinal cord from injury and could explain why none of the surgically treated
Acknowledgments
We thank Marta Rosal, Asiul Chacaltana, Carla Fonseca and Marielle Esteves for their substantial contribution to the study through the care of the sheep and lambs. Funded by a grant (FIS PI040492) from the Spanish Ministry of Health, and Fundació Privada A. Bosch.
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Cited by (0)
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Preliminary results presented at the 17th Annual Meeting of the European Orthopaedic Research Society, in Madrid, Spain, on April 24–26, 2008, and at the 27th Annual Meeting of the International Foetal Medicine and Surgery Society, in Athens, Greece, on September 12–16, 2008.