Original ResearchObstetricsSevere and progressive neuronal loss in myelomeningocele begins before 16 weeks of pregnancy
Section snippets
Study population
We retrospectively collected all postmortem cases of spinal defects following TOP and confirmed by pathologic examination from 1998 to 2018. A signed consent for fetal autopsy was obtained for all cases.
Among these cases of spinal defects, we selected those that met the following features of MMC: open vertebral arch, open arachnoidal sheet, and open ependymal canal. Furthermore, to match the eligibility criteria of most trials on prenatal surgery, we selected cases with a normal karyotype or
Description of the study population
After exclusion of cases with defects at >T1 or <S1, closed defects, and cytogenetic anomalies, 186 cases were included in this study (Figure 3). Gestational age at TOP ranged from 13 to 39.5 weeks. A significant proportion of cases were terminated at an early gestational age with 21 (11.3 %) and 36 (19.4%) cases at ≤16 weeks and 16–20 weeks, respectively (Table 1), whereas most cases were terminated at >24 weeks after midtrimester ultrasound diagnosis. The time between delivery and autopsy in
Comment
This study showed that exposed spinal cord is significantly damaged early in pregnancy and that spinal injury extends cranially with a significant reduction in motor neurons in the adjacent cord right above the defect, which worsens with advancing gestational age at a rate of 16% per week.
A two-hit mechanism has been hypothesized for the neurological damage in MMC: it assumes that the functionally normal, yet dysraphic (first “hit”) exposed spinal cord is progressively destroyed during
Conclusion
Current surgical strategies might benefit from earlier repair to rescue motor neurons within the exposed cord. These procedures could possibly prevent further cranial extension of neuronal loss.
The development of new therapeutic strategies for early in utero repair of MMC could significantly improve neurologic and motor prognosis of these children: early prenatal repair (≤16 weeks) could prevent—better than reverse—Chiari II malformation in 69.3% of cases, rescue the 17% remaining motor neurons
Acknowledgments
The authors thank Professor T Molina (Department of Pathology, Necker-Enfants Malades Hospital, AP-HP and Université de Paris) and Professor A Pierani (Institute of Psychiatry and Neuroscience of Paris, INSERM U1266, & IMAGINE Institute) for coordination assistance. The authors also thank F. Frere, L. Hakkakian, E. Magnin, and E. Lunel (Department of Histology-Embryology and Cytogenetics, Unit of Embryo &fetal pathology, Necker-Enfants Malades Hospital, AP-HP and Paris Descartes University) for
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The authors report no conflict of interest.
Cite this article as: Ben Miled S, Loeuillet L, Van Huyen JD, et al. Severe and progressive neuronal loss in myelomeningocele begins before 16 weeks of pregnancy. Am J Obstet Gynecol 2020;223:256.e1-9.