The New England Journal of Medicine March 17, 2011

A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele

N. Scott Adzick, Elizabeth A. Thom, Catherine Y. Spong, John W. Brock 3rd, et al. (MOMS Investigators)

Bottom Line

Prenatal in utero surgery for fetal myelomeningocele significantly reduced the need for cerebrospinal fluid shunting and improved motor function at 30 months compared to standard postnatal repair, though it increased maternal and fetal risks such as preterm delivery.

Key Findings

1. The trial was stopped early for efficacy after 183 of the planned 200 patients were enrolled.
2. The first primary outcome—a composite of fetal/neonatal death or the need for a cerebrospinal fluid (CSF) shunt by 12 months—occurred in 68% of the prenatal-surgery group compared to 98% of the postnatal-surgery group (Relative Risk [RR], 0.70; 97.7% CI, 0.58 to 0.84; P<0.001).
3. Actual rates of CSF shunt placement were significantly lower in the prenatal-surgery group (40%) compared to the postnatal-surgery group (82%) (RR, 0.48; 97.7% CI, 0.36 to 0.64; P<0.001).
4. Prenatal surgery resulted in a significantly improved composite score for mental development and motor function at 30 months of age (P=0.007).
5. Independent ambulation at 30 months was achieved by 42% of infants in the prenatal-surgery arm compared with 21% in the postnatal-surgery arm (P=0.01).
6. Prenatal surgery was associated with increased risks, notably a higher rate of preterm delivery (average gestational age 34.1 weeks vs. 37.3 weeks) and an increased risk of maternal uterine dehiscence at delivery.

Study Design

Design
Randomized Controlled Trial
Open-Label
Sample
183
Patients
Duration
30 months
Median
Setting
Multicenter, US
Population Pregnant women carrying a singleton fetus diagnosed with myelomeningocele (with an upper lesion boundary between T1 and S1), evidence of hindbrain herniation, a normal karyotype, and a gestational age between 19.0 and 25.9 weeks at randomization.
Intervention Open maternal-fetal surgical repair of the myelomeningocele performed in utero prior to 26 weeks of gestation.
Comparator Standard postnatal surgical repair of the myelomeningocele performed shortly after maternal delivery.
Outcome Two primary outcomes: (1) A composite of fetal or neonatal death or the need for placement of a cerebrospinal fluid (CSF) shunt by 12 months of age; and (2) A composite score of mental development and motor function assessed at 30 months of age.

Study Limitations

The trial utilized an open-label design, as blinding the mothers and surgical teams to the intervention was practically impossible.
Prenatal surgery exposed the mother to significant risks, including an increased risk of uterine dehiscence, necessitating cesarean delivery for the index pregnancy and all subsequent pregnancies.
Infants in the prenatal arm were exposed to the inherent morbidities associated with preterm birth (13% were delivered before 30 weeks of gestation).
The cohort comprised a highly selected group of patients meeting strict inclusion criteria treated at three specialized fetal medicine centers, which may limit the generalizability of the outcomes to lower-volume centers.

Clinical Significance

The MOMS trial firmly established open maternal-fetal surgery as a standard-of-care option for eligible pregnancies complicated by myelomeningocele. It validated the 'two-hit hypothesis,' proving that early intrauterine surgical closure mitigates ongoing secondary neurologic injury caused by prolonged exposure of the spinal cord to amniotic fluid, substantially improving long-term functional independence.

Historical Context

Prior to the MOMS trial, the in utero repair of myelomeningocele was gaining traction based on animal models and early observational human data, which suggested neurological benefit. However, the practice remained highly controversial due to the profound risks imposed on the mother and the lack of rigorous, randomized data. Sponsored by the NICHD, the MOMS trial halted unregulated, unproven procedures and definitively demonstrated the therapeutic value and specific risks of fetal surgery compared to traditional postnatal closure.

Guided Discussion

High-yield insights from every perspective

Med Student
Medical Student

The MOMS trial demonstrates improved outcomes with prenatal repair based on the two-hit hypothesis of myelomeningocele. What are the two hits in this pathophysiologic model, and how does in utero closure prevent secondary complications like Chiari II malformation?

Key Response

The first hit is the primary embryologic failure of neural tube closure. The second hit involves ongoing chemical toxicity from amniotic fluid and mechanical trauma to the exposed spinal cord. Reversing the CSF leak by closing the defect in utero restores normal pressure dynamics, which prevents or reverses hindbrain herniation (Chiari II) that disrupts normal CSF flow, thereby directly reducing the infant's need for ventriculoperitoneal shunting.

Resident
Resident

While counseling a patient at 20 weeks gestation with a newly diagnosed fetal myelomeningocele, how should you balance the fetal benefits of prenatal repair demonstrated in the MOMS trial against the specific maternal and obstetric risks?

Key Response

Residents must master informed consent for complex interventions. Prenatal repair improves infant motor function and halves the need for shunting (40 percent versus 82 percent), but it significantly increases maternal risks such as preterm birth, uterine dehiscence, and placental abruption. It also mandates cesarean delivery for the index and all future pregnancies due to the classical hysterotomy required for the fetal repair.

Fellow
Fellow

The MOMS trial had strict inclusion criteria, such as an upper boundary of 25 weeks and 6 days gestation and specific anatomical lesion limitations. How do lesion level and the presence of severe kyphosis impact the technical feasibility and functional outcomes of fetal repair, and why are these criteria critical for maternal-fetal triage?

Key Response

Fetal surgery requires an optimal window before irreversible neural damage occurs, but late enough for technical feasibility. Severe kyphosis makes primary skin closure nearly impossible without extensive dissection, risking severe fetal blood loss. Higher anatomical lesions often have worse baseline functional prognoses, which fundamentally alters the risk-benefit ratio for exposing a healthy mother to major abdominal surgery and lifelong obstetric risks.

Attending
Attending

The MOMS trial shifted the paradigm of myelomeningocele management, yet creating a fetal surgery program requires immense specialized resources. As an attending, how do you navigate the centralization of fetal surgery centers and coordinate the complex long-term multidisciplinary care required for these children post-delivery?

Key Response

Fetal surgery is high-risk and high-resource, necessitating referral to specialized quaternary centers to replicate the trial safety profile. However, post-delivery and early childhood care involving pediatric neurosurgery, urology, orthopedics, and developmental pediatrics must often be transitioned back to the patient's local community. This highlights the critical importance of robust care-coordination and standardized transition protocols to maintain the initial surgical gains.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD
PhD

The MOMS trial was stopped early by the Data and Safety Monitoring Board after 183 of the planned 200 patients were randomized due to significant efficacy in the primary outcome. What are the methodological risks of stopping a surgical trial early for efficacy, particularly concerning the accurate estimation of rare maternal adverse events?

Key Response

Stopping early for efficacy can exaggerate treatment effects due to random highs and prematurely truncate the collection of crucial safety data. For a highly invasive procedure with severe risks like uterine rupture, a smaller sample size limits the precision of confidence intervals for rare, catastrophic maternal complications, which complicates comprehensive long-term risk modeling and maternal counseling.

Journal Editor
Journal Editor

The trial utilized highly experienced surgeons at only three established quaternary centers. If reviewing a follow-up multi-center implementation study, what methodological safeguards would you require to ensure that the surgical learning curve and outcomes in newly adopting non-trial centers do not mask increased maternal and fetal morbidity?

Key Response

The positive MOMS effect relies heavily on the expertise of highly specific, multidisciplinary surgical teams. A discerning editor must be highly critical of generalizability; widespread adoption without rigorous credentialing, mandatory registry tracking, and strict quality assurance can easily lead to unacceptably high maternal-fetal morbidity that was successfully mitigated in the tightly controlled trial environment.

Guideline Committee
Guideline Committee

Based on the MOMS trial results, ACOG and SMFM guidelines now recommend that maternal-fetal surgery for myelomeningocele be offered as an option to eligible patients. What level of evidence supports this, and what specific institutional and resource criteria must guidelines mandate to safely integrate this procedure into standard obstetric practice?

Key Response

Supported by Level A evidence from this well-conducted RCT, guidelines mandate that this option be discussed with eligible families. However, ACOG/SMFM guidelines strongly emphasize that the procedure should only be performed at multidisciplinary centers with extensive fetal surgery experience, specialized obstetric anesthesia, and high-risk NICU capabilities to strictly mitigate the substantial known risks of extreme prematurity, maternal hemorrhage, and uterine rupture.

Clinical Landscape

Noteworthy Related Trials

1991

MRC Vitamin Study

n = 1,195 · Lancet

Tested

Folic acid supplementation (4 mg daily)

Population

Women with a prior pregnancy affected by a neural tube defect

Comparator

Placebo or vitamins without folic acid

Endpoint

Incidence of neural tube defects in the subsequent pregnancy

Key result: Folic acid supplementation reduced the risk of recurrent neural tube defects by 72 percent.
2004

Eurofoetus Trial

n = 142 · NEJM

Tested

Fetoscopic laser coagulation of chorionic vessels

Population

Pregnant women with severe twin-twin transfusion syndrome

Comparator

Serial amnioreduction

Endpoint

Survival of at least one twin to 28 days of age and survival without neurologic complications at 6 months

Key result: Laser therapy significantly improved the survival rate of at least one twin and reduced neurologic complications compared to serial amnioreduction.
2021

TOTAL Trial

n = 80 · NEJM

Tested

Fetoscopic endoluminal tracheal occlusion (FETO)

Population

Fetuses with severe isolated congenital diaphragmatic hernia

Comparator

Expectant management with postnatal repair

Endpoint

Survival to discharge from the neonatal intensive care unit

Key result: FETO significantly increased survival to discharge compared to expectant care, though it was associated with higher rates of preterm birth.

Tailored to your role

Want this tailored to you?

Add your specialty or training stage to get role-specific takeaways and more questions.

Personalize this analysis