Advertisement
Mayo Clinic Proceedings Home

In Utero Restoration of Hindbrain Herniation in Fetal Myelomeningocele as Part of Prenatal Regenerative Therapy Program at Mayo Clinic

      Abstract

      Objective

      To assess our initial experience with prenatal restoration of hindbrain herniation following in utero repair of myelomeningocele (MMC).

      Patients and Methods

      Three consecutive patients with prenatally diagnosed MMC (between January 1, 2018 and September 30, 2018) were managed with open in utero surgery. As per institutional review board approval and following a protocol designed at the Mayo Clinic Maternal & Fetal Center, fetal intervention was offered between 19 0/7 and 25 6/7 weeks of gestation. Prenatal improvement of hindbrain herniation was the declared restorative end point. Obstetrical and perinatal outcomes were also assessed.

      Results

      Diagnosis of MMC was confirmed upon referral between 20 and 21 weeks’ gestation by using fetal ultrasound and magnetic resonance imaging. In all cases reported here, the spinal defect was lumbosacral with evidence of hindbrain herniation. Open in utero MMC repair was performed between 24 and 25 weeks’ gestation with no notable perioperative complications. Postprocedure fetal magnetic resonance imaging performed 6 weeks after in utero repair documented improvement of hindbrain herniation. Deliveries were at 37 weeks by cesarean section without complications. Most recent postnatal follow-ups were unremarkable at both 11 months (baby 1) and 3 months of age (baby 2), with mild ventriculomegaly. Antenatal and postnatal follow-up of baby 3 at 1 month of age was also unremarkable.

      Conclusion

      Our study highlights the prenatal restoration of hindbrain herniation following in utero MMC repair in all cases presented here as an example of a prenatal regenerative therapy program in our institution.

      Abbreviations and Acronyms:

      CDH (congenital diaphragmatic hernia), IV (intravenous), L (lumbar), MMC (myelomeningocele), MOMS (Management of Myelomeningocele Study), MRI (magnetic resonance imaging), S (sacral)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Adzick N.S.
        • Thom E.A.
        • Spong C.Y.
        • et al.
        • MOMS Investigators
        A randomized trial of prenatal versus postnatal repair of myelomeningocele.
        N Engl J Med. 2011; 364: 993-1004
        • Copp A.J.
        • Adzick N.S.
        • Chitty L.S.
        • Fletcher J.M.
        • Holmbeck G.N.
        • Shaw G.M.
        Spina bifida.
        Nat Rev Dis Primers. 2015; 1: 15007
        • Williams H.
        A unifying hypothesis for hydrocephalus, Chiari malformation, syringomyelia, anencephaly and spina bifida.
        Cerebrospinal Fluid Res. 2008; 5: 7
        • Ruano R.
        • Enninga E.A.L.
        • Brana Rivera P.E.
        • Terzic A.
        Regenerative prophylaxis in utero.
        Clin Pharmacol Ther. 2019; 105: 39-41
        • Ruano R.
        • Klinkner D.B.
        • Balakrishnan K.
        • et al.
        Fetoscopic therapy for severe pulmonary hypoplasia in congenital diaphragmatic hernia: a first in prenatal regenerative medicine at Mayo Clinic.
        Mayo Clin Proc. 2018; 93: 693-700
        • Waldman S.A.
        Prenatal regeneration in clinical practice.
        Mayo Clinic Proc. 2018; 93: 673-675
        • Ruano R.
        • da Silva M.M.
        • Campos J.A.
        • et al.
        Fetal pulmonary response after fetoscopic tracheal occlusion for severe isolated congenital diaphragmatic hernia.
        Obstet Gynecol. 2012; 119: 93-101
        • Ruano R.
        • Yoshisaki C.T.
        • da Silva M.M.
        • et al.
        A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia.
        Ultrasound Obstet Gynecol. 2012; 39: 20-27
        • Nagaraj U.
        • Bierbrauer K.
        • Zhang B.
        • Peiro J.
        • Kline-Fath B.
        Hindbrain herniation in Chiari II malformation on fetal and postnatal MRI.
        AJNR Am J Neuroradiol. 2017; 38: 1031-1036
        • Behfar A.
        • Terzic A.
        Regeneration for all: an odyssey in biotherapy.
        Eur Heart J. 2019; 40: 1033-1035
        • Wyles S.P.
        • Hayden R.E.
        • Meyer F.B.
        • Terzic A.
        Regenerative medicine curriculum for next-generation physicians.
        NPJ Regen Med. 2019; 4: 3
        • Zarutskie A.
        • Guimaraes C.
        • Yepez M.
        • et al.
        Prenatal brain imaging for predicting need for postnatal hydrocephalus treatment in fetuses that had neural tube defect repair in utero.
        Ultrasound Obstet Gynecol. 2019; 53: 324-334
        • Moldenhauer J.S.
        • Soni S.
        • Rintoul N.E.
        • et al.
        Fetal myelomeningocele repair: the post-MOMS experience at the Children's Hospital of Philadelphia.
        Fetal Diagn Ther. 2015; 37: 235-240
        • Moron A.F.
        • Barbosa M.M.
        • Milani H.
        • et al.
        Perinatal outcomes after open fetal surgery for myelomeningocele repair: a retrospective cohort study.
        BJOG. 2018; 125: 1280-1286
        • Lu V.
        • Snyder K.
        • Ibirogba E.
        • Ruano R.
        • Daniels D.J.
        • Ahn E.S.
        Progressive hydrocephalus despite early complete reversal of hindbrain herniation after open myelomeningocele repair.
        Neurosurg Focus. 2019; 47: E13
        • Nagaraj U.D.
        • Bierbrauer K.S.
        • Stevenson C.B.
        • et al.
        Prenatal and postnatal MRI findings in open spinal dysraphism following intrauterine repair via open versus fetoscopic surgical techniques [published online ahead of print July 27, 2019]. Prenat Diagn.
        • Zamłyński J.
        • Olejek A.
        • Koszutski T.
        • et al.
        Comparison of prenatal and postnatal treatments of spina bifida in Poland–a non-randomized, single-center study.
        J Matern Fetal Neonatal Med. 2014; 27: 1409-1417
        • Johnson M.P.
        • Bennett K.A.
        • Rand L.
        • et al.
        • Management of Myelomeningocele Study Investigators
        The Management of Myelomeningocele Study: obstetrical outcomes and risk factors for obstetrical complications following prenatal surgery.
        Am J Obstet Gynecol. 2016; 215: 778.e771-778.e779
        • Pedreira D.A.
        • Zanon N.
        • Nishikuni K.
        • et al.
        Endoscopic surgery for the antenatal treatment of myelomeningocele: the CECAM trial.
        Am J Obstet Gynecol. 2016; 214: 111.e1-111.e11