Fetal surgery for spina bifida publications

Fetal surgery for spina bifida publications

Staff of the Center for Fetal Diagnosis and Treatment have written extensively about fetal surgery for spina bifida. These articles in peer-reviewed publications show the long legacy of CHOP research into fetal surgery for myelomeningocele, the most severe form of spina bifida, as well as our team's contributions to the new treatments available to patients with myelomeningocele, the most severe form of spina bifida.

Establishing fetal surgery for spina bifida as a standard of care

In 2011, a study published in the New England of Journal of Medicine outlined the results of the MOMS (Management of Myelomeningocele) Study and established fetal surgery for spina bifida as a new standard of care.

Adzick NS, Thom EA, Spong CY, Brock III JW, Burrows PK, Johnson MP, et al. "A randomized trial of prenatal versus postnatal repair of myelomeningocele." N Engl J Med 2011; 364:993-1004. Cited in PubMed; PMID 21306277.

MOMS2 Study Findings

In 2020, researchers published new findings in follow-up study known as “MOMS2: Follow up of the Management Of Myelomeningocele Study.” These findings, published in Pediatrics, show significant physical and emotional benefits a decade later in school-age children who received corrective surgery in the womb for myelomeningocele.

Houtrow AJ, Thom EA, Fletcher JM, Burrows PK, Adzick NS, Thomas NH, Brock III JW, Cooper T, Lee H, Bilaniuk L, Glenn OA, Pruthi S, MacPherson C, Farmer DL, Johnson MP, Howell LJ, Gupta N, Walker WO. “Prenatal Repair of Myelomeningocele and School-Age Functional Outcomes.” Pediatrics, online January 24, 2020.

MOMS3

Phase three of the study — known as “Follow-up in the Teen and Young Adult Years to the Management of Myelomeningocele Study: MOMS3” — is now enrolling participants. MOMS3 will continue to follow this same group of children until they are 15 to 24 years old. Learn more about this next phase of the MOMS trial.

Recent reports on fetal surgery for spina bifida

2020

Rintoul NE, Keller RL, Walsh WF, Burrows PK, Thom EA, Kallan MJ, Howell LJ, Adzick NS, MOMS Investigators. The Management of Myelomeningocele Study: Short-Term Neonatal Outcomes. Fetal Diagn Ther. 2020 Aug 31;1-8. doi: 10.1159/000509245. PMID: 32866951

2019

Moldenhauer JS, Flake AW. Open fetal surgery for neural tube defects. Best Pract Res Clin Obstet Gynaecol. 2019 Mar 18;. [Epub ahead of print] PMID: 31078425

Brock JW 3rd, Thomas JC, Baskin LS, Zderic SA, Thom EA, Burrows PK, Lee H, Houtrow AJ, Macpherson C, Adzick NS. Effect of Prenatal Repair of Myelomeningocele on Urological Outcomes at School Age. J Urol. 2019 May 10; [Epub ahead of print] PMID: 31075056 

2018

Antiel RM, Janvier A, Feudtner C, Blaine K, Fry J, Howell LJ, Houtrow AJ. The experience of parents with children with myelomeningocele who underwent prenatal surgery. J Pediatr Rehabil Med. 2018 Nov 18;. PMID: 30507587 

Farmer DL, Adzick NS. Reply to Manuscript # L18-092AR1 "A clinician's concerns about motor functions Outcomes of fetal Surgery for Myelomeningocele." Am J Obstet Gynecol. 2018 Sep 21; [Epub ahead of print] PMID: 30248309

Fraga MV, Giaccone A, Adzick NS. Respiratory morbidities in late preterm and term infants with myelomeningocele. J Perinatol. 2018 Aug 30;. [Epub ahead of print] PMID: 30166620 [PubMed - as supplied by publisher]

Joyeux L, Danzer E, Flake AW, Deprest J. Fetal surgery for spina bifida aperta. Arch Dis Child Fetal Neonatal Ed. 2018 Jul 13. pii: fetalneonatal-2018-315143. doi: 10.1136/archdischild-2018-315143. [Epub ahead of print]

Farmer DL, Thom EA, Brock JW, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Gupta N, Adzick NS for the MOMS Investigators. Management of Myelomeningocele Study Investigators. The Management of Myelomeningocele Study: full cohort 30-month pediatric outcomes. Am J Obstet Gynecol. 2018 Feb;218(2): Epub 2017 Dec 12. PMID: 29246577

2017

Moldenhauer JS, Adzick NS. Fetal surgery for myelomeningocele: After the Management of Myelomeningocele Study (MOMS). Semin Fetal Neonatal Med. 2017 Oct 11. pii: S1744-165X(17)30093-8. doi: 10.1016/j.siny.2017.08.004. [Epub ahead of print]

Kim AG, Danzer E, Moldenhauer JS, Khalek N, McClain LE, Waqar LN, Hedrick HL, Johnson MP, Adzick NS, Peranteau WH, Flake AW. Amniotic Fluid Concentrations of Glial Fibrillary Acidic Protein Do Not Correlate with Prenatal Metrics in Fetuses with Myelomeningocele. Fetal Diagn Ther. 2017 Jul 29. Doi: 10.1159/000478258. [Epub ahead of print].

Heuer GG, Moldenhauer JS, Adzick NS. Prenatal surgery for myelomeningocele: review of the literature and future directions. Childs Nerv Syst. 2017 Jul;33(7):1149-1155. Doi: 10.1007/s00381-017-3440-z. Epub 2017 May 17.

2016

Johnson MP, Bennett KA, Rand L, Burrows PK, Thom EA, Thom LJ, Farrell JA, Dabrowiak ME, Brock JW 3rd, Farmer DL, Adzick NS, 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 Aug 2. pii: S0002-9378(16)30526-9. doi: 10.1016/j.ajog.2016.07.052. 

Antiel RM, Adzick NS, Thom EA, Burrows PK, Farmer DL, Brock JW 3rd, Howell LJ, Farrell JA, Houtrow AJ; Management of Myelomeningocele Study Investigators. Impact on family and parental stress of prenatal vs postnatal repair of myelomeningocele. Am J Obstet Gynecol. 2016 Jun 2. pii: S0002-9378(16)30264-2. doi: 10.1016/j.ajog.2016.05.045.

Danzer E, Thomas NH, Thomas A, Friedman KB, Gerdes M, Koh J, Adzick NS, Johnson MP. Long-term neurofunctional outcome, executive functioning, and behavioral adaptive skills following fetal myelomeningocele surgery. Am J Obstet Gynecol. 2016 Feb;214(2):269.e1-8.

2015

Tulipan N, Wellons JC 3rd, Thom EA, Gupta N, Sutton LN, Burrows PK, Farmer D, Walsh W, Johnson MP, Rand L, Tolivaisa S, D'alton ME, Adzick NS; for the MOMS Investigators. Prenatal surgery for myelomeningocele and the need for cerebrospinal fluid shunt placement. J Neurosurg Pediatr. 2015 Dec;16(6):613-20.

Soni S, Moldenhauer JS, Spinner SS, Rendon N, Khalek N, Martinez-Poyer J, Johnson MP, Adzick NS. Chorioamniotic Membrane Separation and Preterm Premature Rupture of Membranes Complicating In Utero Myelomeningocele Repair. Am J Obstet Gynecol. 2015 Dec 12.

Brock JW 3rd, Carr MC, Adzick NS, Burrows PK, Thomas JC, Thom EA, Howell LJ, Farrell JA, Dabrowiak ME, Farmer DL, Cheng EY, Kropp BP, Caldamone AA, Bulas DI, Tolivaisa S, Baskin LS; MOMS Investigators. Bladder Function After Fetal Surgery for Myelomeningocele. Pediatrics. 2015 Oct;136(4):e906-13.

Moldenhauer JS, Soni S, Rintoul NE, Spinner SS, Khalek N, Martinez-Poyer J, Flake AW, Hedrick HL, Peranteau WH, Rendon N, Koh J, Howell LJ, Heuer GG, Sutton LN, Johnson MP, Adzick NS. Fetal Myelomeningocele Repair: The Post-MOMS Experience at the Children's Hospital of Philadelphia. Fetal Diagn Ther. 2015;37(3):235-40. Epub 2014 Aug 15.

2014

Heuer GG, Adzick NS, Sutton LN. Fetal myelomeningocele closure: technical considerations. Fetal Diagn Ther. Aug 2014.

Jackson EM, Schwartz DM, Sestokas AK, Zarnow DM, Adzick NS, Johnson MP, Heuer GG, Sutton LN. Intraoperative neurophysiological monitoring in patients undergoing tethered cord surgery after fetal myelomeningocele repair. J Neurosurg Pediatr. 2014 Apr;13(4):355-61. doi: 10.3171/2014.1.PEDS11336. Epub 2014 Feb 7.

2013

Adzick NS. Fetal surgery for spina bifida: past, present, future. Semin Pediatr Surg. 2013 Feb;22(1):10-7. doi: 10.1053/j.sempedsurg.2012.10.003. Cited in PubMed; PMID 23395140.

2012

Adzick NS. Fetal surgery for myelomeningocele: trials and tribulations. J Pediatr Surg. 2012 Feb;47(2):273-81. Cited in PubMed; PMID 22325376.

Danzer E, Johnson MP, Adzick NS. Fetal surgery for myelomeningocele: progress and perspectives. Dev Med Child Neurol. 2012 Jan;54(1):8-14. doi: 10.1111/j.1469-8749.2011.04049.x. Epub 2011 Jul 11. Review. Cited in PubMed; PMID 21745203.

2011

Bebbington MW, Danzer E, Johnson MP, Adzick NS. Open fetal surgery for myelomeningocele. Prenat Diagn. 2011 Jul;31(7):689-94. doi: 10.1002/pd.2805. Epub 2011 Jun 8. Cited in PubMed; PMID 21656790.

Danzer E, Gerdes M, Bebbington MW, Koh J, Adzick SN, Johnson MP. Fetal myelomeningocele surgery: preschool functional status using the Functional Independence Measure for children (WeeFIM). Childs Nerv Syst. 2011 Jul;27(7):1083-8. Epub 2011 Feb 16. Cited in PubMed; PMID:21327591.

Grant RA, Heuer GG, Carrión GM, Adzick NS, Schwartz ES, Stein SC, et al. Morphometric analysis of posterior fossa after in utero myelomeningocele repair. J Neurosurg Pediatr. 2011 Apr;7(4):362-8. Cited in PubMed; PMID 21456906.

Danzer E, Adzick NS. Fetal surgery for myelomeningocele: Patient selection, perioperative management and outcomes. Fetal Diagn Ther. 2011;30(3):163-73. Cited in PubMed; PMID 21849764.

Danzer E, Gerdes M, Bebbington MW, Koh J, Adzick NS, Johnson MP. Preschool neurobehavioral outcome following fetal myelomeningocele surgery. Fetal Diagn Ther. 2011;30(3):174-9. Epub 2011 Sep 8. Cited in PubMed; PMID 21912086.

Establishing the baseline shunt percentages for children with standard postnatal myelomeningocele repair

This baseline data for children with myelomeningocele (MMC) treated after birth and followed in the CHOP Spina Bifida Clinic was used for the postnatal repair group in the statistical formulation of the MOMS Trial.

Advancing fetal surgery: Establishing intraoperative fetal echocardiographic monitoring as a standard of care

Rychik J, Cohen D, Tran KM, Szwast A, Natarajan SS, Johnson MP, Moldenhauer JS, Khalek N, Martinez-Poyer J, Flake AW, Hedrick HL, Adzick NS. The Role of Echocardiography in the Intraoperative Management of the Fetus Undergoing Myelomeningocele Repair. Fetal Diagn Ther. 2014 Jul 18. [Epub ahead of print]

Rychik J, Tian Z, Cohen MS, Ewing SG, Cohen D, Howell LJ, et al. Acute cardiovascular effects of fetal surgery in the human. Circulation. 2004 Sep 21;110(12):1549-56. Epub 2004 Sep 7.

Important maternal follow-up after fetal surgery at CHOP

Wilson RD, Lemerand K, Johnson MP, Flake AW, Bebbington M, Hedrick HL, et al. Reproductive outcomes in subsequent pregnancies after a pregnancy complicated by open maternal-fetal surgery (1996-2007). Am J Obstet Gynecol. 2010 Sep;203(3):209.e1-6. Cited in PubMed; PMID 20537307.

Wilson RD, Johnson MP, Flake AW, Crombleholme TM, Hedrick HL, Wilson J, et al. Reproductive outcomes after pregnancy complicated by maternal-fetal surgery. Am J Obstet Gynecol. 2004 Oct;191(4):1430-6. Cited in PubMed; PMID 15507978.

Wilson RD, Johnson MP, Crombleholme TM, Flake AW, Hedrick HL, King M, et al. Chorioamniotic membrane separation following open fetal surgery: pregnancy outcome. Fetal Diagn Ther. 2003 Sep-Oct;18(5):314-20. Cited in PubMed; PMID 12913340.

Clinical outcomes for pre-MOMS fetal surgery myelomeningocele patients from CHOP

Danzer E, Finkel R, Gerdes M, Schwartz EM, Rintoul NN, Adzick NS, et al. The relationship of seizure activity and chronic epilepsy in early infancy and short-term neurodevelopmental outcome following fetal myelomeningocele closure. Neuropediatrics. 2010 Jun;41(3):140-3. Epub 2010 Sep 21. Cited in PubMed; PMID 20859834.

Danzer E, Gerdes M, Bebbington MW, Zarnow DN, Adzick NS, Johnson MP. Preschool neurodevelopmental outcome of children following fetal myelomeningocele closure. Am J Obstet Gynecol. 2010 May;202(5):450.e1-9. Epub 2010 Mar 29. Cited in PubMed; PMID 20347433.

Danzer E, Ernst LM, Rintoul NE, Johnson MP, Adzick NS, Flake AW. In utero meconium passage in fetuses and newborns with myelomeningocele. J Neurosurg Pediatr. 2009 Feb;3(2):141-6. Cited in PubMed; PMID 19278315.

Danzer E, Gerdes M, Bebbington MW, Sutton LN, Melchionni J, Adzick NS, et al. Lower extremity neuromotor function and short-term ambulatory potential following in utero myelomeningocele surgery. Fetal Diagn Ther. 2009;25(1):47-53. Epub 2009 Jan 28. Cited in PubMed; PMID 19174610.

Danzer E, Finkel RS, Rintoul NE, Bebbington MW, Schwartz ES, Zarnow DM, et al. Reversal of hindbrain herniation after maternal-fetal surgery for myelomeningocele subsequently impacts on brain stem function. Neuropediatrics. 2008 Dec;39(6):359-62. Epub 2009 Jun 30. Cited in PubMed; PMID 19569004.

Danzer E, Adzick NS, Rintoul NE, Zarnow DM, Schwartz ES, Melchionni J, et al. Intradural inclusion cysts following in utero closure of myelomeningocele: clinical implications and follow-up findings. J Neurosurg Pediatr. 2008 Dec;2(6):406-13. Cited in PubMed; PMID 19035686.

Carr MC. Fetal myelomeningocele repair: urologic aspects. Curr Opin Urol.2007 Jul;17(4):257-62. Cited in PubMed; PMID 17558269.

Danzer E, Johnson MP, Bebbington M, Simon EM, Wilson RD, Bilaniuk LT. Fetal head biometry assessed by fetal magnetic resonance imaging following in utero myelomeningocele repair. Fetal Diagn Ther. 2007;22(1):1-6. Epub 2006 Sep 21. Cited in PubMed; PMID 17003546.

Johnson MP, Gerdes M, Rintoul N, Pasquariello P, Melchionni J, Sutton LN, et al. Maternal-fetal surgery for myelomeningocele: Neurodevelopmental outcomes at 2 years of age. Am J Obstet Gynecol. 2006 Apr;194(4):1145-50; discussion 1150-2. Cited in PubMed; PMID 16580316.

Danzer E, Johnson MP, Wilson RD, Flake AW, Hedrick HL, Sutton LN, et al. Fetal head biometry following in-utero repair of myelomeningocele. Ultrasound Obstet Gynecol. 2004 Nov;24(6):606-11. Cited in PubMed; PMID 15517548.

Johnson MP, Sutton LN, Rintoul N, Crombleholme TM, Flake AW, Howell LJ, et al. Fetal myelomeningocele repair: short-term clinical outcomes. Am J Obstet Gynecol.2003 Aug;189(2):482-7. Cited in PubMed; PMID 14520222.

Tulipan N, Sutton LN, Bruner JP, Cohen BM, Johnson M, Adzick NS. The effect of intrauterine myelomeningocele repair on the incidence of shunt-dependent hydrocephalus. Pediatr Neurosurg.2003 Jan;38(1):27-33. Cited in PubMed; PMID 12476024.

Early research related to prenatal myelomeningocele repair

Adzick NS. Fetal myelomeningocele: Natural history, pathophysiology, and in-utero intervention. Semin Fetal Neonatal Med. 2010 Feb;15(1):9-14. Epub 2009 Jun 18. Cited in PubMed; PMID 19540177.

Mitchell LE, Adzick SN, Melchionne J, Pasquariello PS, Sutton LN, Whitehead AS. Spina bifida. Lancet. 2004 Nov 20-26;364(9448):1885-95. Cited in PubMed; PMID 15555669.

Bouchard S, Davey MG, Rintoul NE, Walsh DS, Rorke LB, Adzick SN. Correction of hindbrain herniation and anatomy of the vermis after in utero repair of myelomeningocele in sheep. J Pediatr Surg. 2003 Mar;38(3):451-8; disc 451-8. Cited in PubMed; PMID 12632366. (This work confirmed the pathophysiology of hindbrain herniation.)

Sutton LN, Adzick NS, Bilaniuk LT, Johnson MP, Crombleholme TM, Flake AW. Improvement in hindbrain herniation demonstrated by serial fetal magnetic resonance imaging following fetal surgery for myelomeningocele. JAMA. 1999 Nov 17;282(19):1826-31. Cited in PubMed; PMID 10573273.

Adzick NS, Sutton LN, Crombleholme TM, Flake AW. Successful fetal surgery for spina bifida. Lancet. 1998 Nov 21;352(9141):1675-6. See the case study.

Meuli M, Meuli-Simmen C, Hutchins GM, Seller MJ, Harrison MR, Adzick NS. The spinal cord lesion in human fetuses with myelomeningocele: implications for fetal surgery. J Pediatr Surg. 1997 Mar;32(3):448-52. Cited in PubMed; PMID 9094015. (Further support of the “two-hit hypothesis” was shown in human fetuses.)

Meuli M, Meuli-Simmen C, Hutchins GM, Yingling CD, Hoffman KM, Harrison MR, et al. In utero surgery rescues neurologic function at birth in sheep with spina bifida. Nat Med. 1995 Apr;1(4):342-7. Cited in PubMed; PMID 7585064. (This article provides the most important experimental “proof of principle” contribution for the “two-hit hypothesis.")

Fetal myelomeningocele laboratory research

Oliver ER, Heuer GG, Thom EA, Burrows PK, Didier RA, DeBari SE, Martin-Saavedra JS, Moldenhauer JS, Jatres J, Howell LJ, Adzick NS, Coleman BG. Myelomeningocele Sac Associated With Worse Lower-Extremity Neurological Sequelae: Evidence for Prenatal Neural Stretch Injury? Ultrasound Obstet Gynecol. 2020 Jun;55(6):740-746. doi: 10.1002/uog.21891.

Watanabe M, Li H, Roybal JL, Santore MT, Radu A, Jo JI, et al. A tissue engineering approach for prenatal closure of myelomeningocele: Comparison of gelatin sponge and microsphere scaffolds and bioactive protein coatings. Tissue Eng Part A. 2011 Jan. 31. Cited in PubMed; PMID 21128864.

Bebbington MW, Danzer E, Johnson MP, Adzick NS. Open fetal surgery for myelomeningocele. Prenat Diagn. 2011 Jul;31(7):689-94. doi: 10.1002/pd.2805. Epub 2011 Jun 8. Review. Cited in PubMed; PMID 21656790.

Danzer E, Adzick NS. Fetal surgery for myelomeningocele: patient selection, perioperative management and outcomes. Fetal Diagn Ther. 2011;30(3):163-73. Cited in PubMed; PMID 21849764.

Grant RA, Heuer GG, Carrión GM, Adzick NS, Schwartz ES, Stein SC, et al. Morphometric analysis of posterior fossa after in utero myelomeningocele repair. J Neurosurg Pediatr. 2011 Apr;7(4):362-8. Cited in PubMed; PMID 21456906.

Danzer E, Zhang L, Radu A, Bebbington MW, Liechty KW, Adzick NS, et al. Amniotic fluid levels of glial fibrillary acidic protein in fetal rats with retinoic acid induced myelomeningocele: A potential marker for spinal cord injury. Am J Obstet Gynecol. 2011 Feb;204(2):178.e1-178.e11. Cited in PubMed; PMID 21284970.

Watanabe M, Jo J, Radu A, Kaneko M, Tabata Y, Flake AW. A tissue engineering approach for prenatal closure of myelomeningocele with gelatin sponges incorporating basic fibroblast growth factor. Tissue Eng Part A. 2010 May;16(5):1645-55. Cited in PubMed; PMID 19954327.

Danzer E, Radu A, Robinson LD, Volpe MV, Adzick NS, Flake AW. Morphologic analysis of the neuromuscular development of the anorectal unit in fetal rats with retinoic acid induced myelomeningocele. Neurosci Lett. 2008 Jan 10;430(2):157-62. Epub 2007 Nov 17. Cited in PubMed; PMID 18063303.

Danzer E, Kiddoo DA, Redden RA, Robinson L, Radu A, Zderic SA, et al. Structural and functional characterization of bladder smooth muscle in fetal rats with retinoic acid-induced myelomeningocele. Am J Physiol Renal Physiol. 2007 Jan;292(1):F197-206. Epub 2006 Aug 29. Cited in PubMed; PMID 16940565.

Danzer E, Schwarz U, Wehrli S, Radu A, Adzick NS, Flake AW. Retinoic acid induced myelomeningocele in fetal rats: Characterization by histopathological analysis and magnetic resonance imaging. Exp Neurol. 2005 Aug;194(2):467-75. Cited in PubMed; PMID 15893307.

Yingling CD, Meuli-Simmen C, Meuli M, Timmel GB, Harrison M, Adzick NS. Experimental fetal neurosurgery: effects of in-utero manipulations on somatosensory evoked potentials. Pediatr Surg Int. 1999;15(8):535-9. Cited in PubMed; PMID 10631727.

Yingling CD, Meuli-Simmen C, Meuli M, Timmel GB, Adzick NS, Harrison M. Assessment of sensory function in neonatal sheep with somatosensory evoked potentials: methodology and normative data. Pediatr Surg Int. 1999;15(8):530-4. Cited in PubMed; PMID 10631726.

Meuli M, Meuli-Simmen C, Yingling CD, Hutchins GM, Timmel GB, Harrison MR, et al. In utero repair of experimental myelomeningocele saves neurological function at birth.  J Pediatr Surg. 1996 Mar;31(3):397-402. Cited in PubMed; PMID 8708911.

Meuli M, Meuli-Simmen D, Yingling CD, Hutchins GM, Hoffman KM, Harrison MR, et al. Creation of myelomeningocele in utero: A model of functional damage from spinal cord exposure in fetal sheep. J Pediatr Surg. 1995 Jul;30(7):1028-32; discussion 1032-3. Cited in PubMed; PMID 7472926.

Meuli-Simmen C, Meuli M, Hutchins GM, Harrison MR, Buncke HJ, Sullivan KM, et al. Fetal reconstructive surgery: experimental use of the latissimus dorsi flap to correct myelomeningocele in utero. Plast Reconstr Surg. 1995 Oct;96(5):1007-11. Cited in PubMed; PMID 7568473.