Management of Myelomeningocele Study (MOMS)

• Infant death or need for ventricular shunt by 1 year of life [ Time Frame: 12 months of age ] [ Designated as safety issue: No ]
• Bayley Scales of Infant Development MDI and functional-anatomical level of lesion at 30 months of age [ Time Frame: 30 months of age ] [ Designated as safety issue: No ]
• Follow-up primary outcome (MOMS2): Vineland Scales of Adaptive Behavior [ Time Frame: Age 5 to 9 ] [ Designated as safety issue: No ]

• motor function
• developmental progress
• bladder development
• renal development
• brain development

• Chiari II malformation [ Time Frame: 12 months ] [ Designated as safety issue: No ]
• Neurodevelopmental status [ Time Frame: 30 months of age ] [ Designated as safety issue: No ]
• Ambulation status, neuromuscular defects [ Time Frame: 30 months of age ] [ Designated as safety issue: No ]
• Maternal, psychological and reproductive functioning [ Time Frame: 30 months postpartum ] [ Designated as safety issue: No ]
• Follow-up secondary outcome (MOMS2): Cognition [ Time Frame: Age 5 to 9 ] [ Designated as safety issue: No ]
• Follow-up secondary outcome (MOMS2): Motor function [ Time Frame: Age 5 to 9 ] [ Designated as safety issue: No ]
• Follow-up secondary outcome (MOMS2): Brain morphology and function [ Time Frame: Age 5 to 9 ] [ Designated as safety issue: No ]
• Follow-up secondary outcome (MOMS2): Urologic outcomes [ Time Frame: Age 5 to 9 ] [ Designated as safety issue: No ]
• Follow-up secondary outcome (MOMS2): Spina bifida associated outcomes [ Time Frame: Age 5 to 9 ] [ Designated as safety issue: No ]
• Follow-up secondary outcome (MOMS2): Quality of life [ Time Frame: Age 5 to 9 ] [ Designated as safety issue: No ]
• Follow-up secondary outcome (MOMS2): Maternal reproductive functioning [ Time Frame: Age 5 to 9 ] [ Designated as safety issue: No ]

Spina bifida (myelomeningocele) is a complex birth defect in which a portion of the spinal cord is not fully developed. The overlying bones and skin are incompletely formed and the underdeveloped area of the spinal cord is exposed on the surface of the back. Spina bifida defects are closed soon after birth to prevent further damage to the spinal cord and nerves. The Management of Myelomeningocele Study (MOMS) is a research study comparing two approaches to the treatment of babies with spina bifida: surgery before birth (prenatal surgery) and the standard closure, surgery after birth (postnatal surgery).

Since 1997, more than 200 fetuses have had in utero closure of myelomeningocele by open maternal-fetal surgery. Preliminary clinical evidence suggests that this procedure reduces the incidence of shunt-dependent hydrocephalus and restores the cerebellum and brainstem to more normal configuration. However, clinical results of prenatal surgery for myelomeningocele are based on comparisons with historical controls and examine only efficacy, not safety. MOMS will determine if intrauterine repair of fetal myelomeningocele at 19 to 25 weeks of gestation improves outcomes as compared to standard postnatal repair. Outcomes assessed include death, the need for ventricular decompressive shunting by one year of life and neurologic function at 30 months of age.

Two hundred women, whose fetuses have spina bifida, will be enrolled in the study and randomized to have either prenatal surgery or postnatal surgery. After a central screening process which includes a medical record review, all women will have an extensive baseline evaluation that will include ultrasound, MRI, physical exam, social work evaluation, psychological screening, and education about spina bifida and prenatal surgery.

For women who are eligible following the central screening process, all screening, surgery and follow-up visits will be performed at one of three MOMS Centers. The mother, if eligible, and her support person will travel (at the expense of the study) to the MOMS Center for screening and randomization.

Women assigned to have prenatal surgery will be scheduled for surgery within 1 to 3 days after they are randomized. They will stay near the MOMS Center until they deliver. Women in the postnatal group will travel back to their assigned MOMS Center to deliver. Both groups will deliver their babies by C-section around the 37th week of their pregnancies. Babies born to women in the postnatal surgery group will have their spina bifida defects closed when they are medically stable, usually within 48 hours of birth.

Children and their parents will return to their assigned MOMS Center at 1 year and 2 ½ years of age for follow-up evaluation. Motor function, developmental progress, and bladder, kidney, and brain development will be assessed. The children will be asked to return for an additional follow-up visit (MOMS2) between the ages of 5 to 8. This follow-up is to determine whether children who received the surgery before birth have better health and mental outcomes and live more independently and function more safely and appropriately in daily life than those who received the surgery after birth.

• Meningomyelocele
• Spinal Dysraphism

• Procedure: Prenatal Myelomeningocele Repair Surgery
  Fetal surgery to repair spina bifida defect performed prior to 26 weeks of gestation with delivery by C-section at approximately 37 weeks of gestation.
• Procedure: Postnatal Myelomeningocele Repair Surgery
  Standard postnatal surgical closure of the spina bifida defect

• Experimental: 1
  Fetal surgery to close spina bifida defect prior to 26 weeks of gestation with delivery by C-Section at approximately 37 weeks of gestation.
  Intervention: Procedure: Prenatal Myelomeningocele Repair Surgery
• Active Comparator: 2
  Standard postnatal closure of the spina bifida defect when the baby is medically stable, usually within 48 hours of birth by C-section.
  Intervention: Procedure: Postnatal Myelomeningocele Repair Surgery

• Adzick NS, Thom EA, Spong CY, Brock JW, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D'Alton ME, Farmer DL; the MOMS Investigators. A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele. N Engl J Med. 2011 Feb 9; [Epub ahead of print]
• Michejda M, McCollough D. New animal model for the study of neural tube defects. Z Kinderchir. 1987 Dec;42 Suppl 1:32-5.
• Heffez DS, Aryanpur J, Rotellini NA, Hutchins GM, Freeman JM. Intrauterine repair of experimental surgically created dysraphism. Neurosurgery. 1993 Jun;32(6):1005-10.
• Paek BW, Farmer DL, Wilkinson CC, Albanese CT, Peacock W, Harrison MR, Jennings RW. Hindbrain herniation develops in surgically created myelomeningocele but is absent after repair in fetal lambs. Am J Obstet Gynecol. 2000 Nov;183(5):1119-23.
• Tulipan N, Bruner JP, Hernanz-Schulman M, Lowe LH, Walsh WF, Nickolaus D, Oakes WJ. Effect of intrauterine myelomeningocele repair on central nervous system structure and function. Pediatr Neurosurg. 1999 Oct;31(4):183-8.
• 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.
• 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.
• Meuli M, Meuli-Simmen C, Hutchins GM, Yingling CD, Hoffman KM, Harrison MR, Adzick NS. In utero surgery rescues neurological function at birth in sheep with spina bifida. Nat Med. 1995 Apr;1(4):342-7.

Inclusion Criteria

• Pregnant women carrying a fetus diagnosed with myelomeningocele
• Myelomeningocele lesion that starts no higher than T1 and no lower than S1 with hindbrain herniation present
• Gestational age at randomization of 19 weeks 0 days to 25 weeks 6 days
• Normal karyotype
• Singleton pregnancy
• United States resident
• Able to travel to study site for study evaluation, procedures, and visits (if randomized to prenatal surgery, must stay near center until delivery)
• Support person to travel and stay with participant

Exclusion Criteria

• Maternal insulin-dependent pregestational diabetes
• Short or incompetent cervix or cervical cerclage
• Placenta previa
• Body mass index of 35 or more
• Previous spontaneous delivery prior to 37 weeks
• Maternal HIV, Hepatitis-B or Hepatitis-C status positive
• Uterine anomaly
• Maternal medical condition which is a contraindication to surgery or general anesthesia
• Other fetal anomaly