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 III, et al.

Bottom Line

The MOMS trial demonstrated that prenatal surgical repair of myelomeningocele significantly improves motor and neurologic outcomes in children while reducing the need for cerebrospinal fluid shunting, albeit at the cost of increased maternal and fetal morbidity related to preterm delivery.

Key Findings

1. Prenatal surgery significantly reduced the primary composite outcome of fetal or neonatal death or the need for a cerebrospinal fluid (CSF) shunt at 12 months (68% vs 98%; relative risk 0.70; 97.7% CI, 0.58 to 0.84; P < 0.001).
2. The actual rate of CSF shunt placement at 12 months was significantly lower in the prenatal group compared to the postnatal group (40% vs 82%; relative risk 0.48; 97.7% CI, 0.36 to 0.64; P < 0.001).
3. Children undergoing prenatal repair showed improved mental and motor development at 30 months compared to those in the postnatal group (P = 0.007).
4. Prenatal intervention was associated with an increased risk of maternal and fetal complications, including higher rates of preterm birth before 30 weeks (13% vs 0%) and uterine dehiscence at delivery.
5. Prenatal repair demonstrated a reversal of hindbrain herniation in a significant proportion of fetuses by the 12-month evaluation.

Study Design

Design
RCT
Open-Label
Sample
183
Patients
Duration
30 mo
Median
Setting
Multicenter, US
Population Pregnant women with a singleton pregnancy and a fetus diagnosed with an isolated myelomeningocele at a gestational age of 19 to 26 weeks.
Intervention Prenatal surgical repair of the myelomeningocele defect performed before 26 weeks of gestation.
Comparator Standard postnatal surgical repair, usually performed within 24 hours of birth.
Outcome Composite of fetal or neonatal death or the need for a cerebrospinal fluid shunt by 12 months; composite score of mental and motor development at 30 months.

Study Limitations

The trial was stopped early for efficacy, which may limit the precision of secondary outcome estimates.
The study was limited to non-obese women with singleton pregnancies and isolated myelomeningocele, potentially limiting generalizability to broader populations.
The procedure requires highly specialized surgical expertise, which may not be universally available.
The increased risk of preterm birth and potential long-term maternal uterine morbidity necessitated careful risk-benefit counseling.

Clinical Significance

This landmark study established prenatal surgery as a viable and superior standard of care for selected fetuses with myelomeningocele, fundamentally shifting the management paradigm from postnatal to prenatal intervention for this condition to improve functional long-term outcomes.

Historical Context

Before this trial, myelomeningocele was managed exclusively with postnatal surgical closure. While early observational reports suggested that intrauterine intervention might prevent secondary neurologic damage from amniotic fluid exposure and mitigate Chiari II malformations, robust evidence from a randomized controlled trial was lacking until the MOMS trial provided the necessary data to validate the intervention's efficacy.

Guided Discussion

High-yield insights from every perspective

Med Student
Medical Student

Explain the 'two-hit hypothesis' regarding the pathophysiology of myelomeningocele and how prenatal surgery addresses this mechanism differently than postnatal surgery.

Key Response

The first 'hit' is the failure of neural tube closure during the fourth week of gestation. The second 'hit' is the progressive damage caused by exposure of the neural elements to amniotic fluid and mechanical trauma in utero. Prenatal surgery aims to mitigate the 'second hit' by covering the spinal cord early, whereas postnatal surgery only addresses the defect after the secondary damage has already occurred.

Resident
Resident

What are the primary clinical benefits demonstrated by the MOMS trial for the infant, and what is the specific maternal morbidity risk that necessitates a mandatory mode of delivery for all future pregnancies?

Key Response

The trial showed a significant reduction in the need for ventriculoperitoneal shunting and improved motor function (walking without orthotics). However, the hysterotomy required for prenatal repair increases the risk of uterine dehiscence or rupture, requiring that all future deliveries be performed via scheduled Cesarean section before the onset of labor.

Fellow
Fellow

Critically analyze the impact of prenatal myelomeningocele repair on the Chiari II malformation. How did the trial measure this, and what were the implications for the neonate's respiratory and feeding status?

Key Response

The MOMS trial found that prenatal repair resulted in a significant reversal of hindbrain herniation (the hallmark of Chiari II). By restoring the pressure gradient and stopping CSF leak at the spinal level, the brainstem can relocate superiorly, potentially reducing the incidence of brainstem-related complications like stridor, apnea, and dysphagia.

Attending
Attending

The MOMS trial demonstrated clear neurologic benefits for the child, but at the cost of maternal morbidity. How should a multidisciplinary center standardize the counseling process to ensure an unbiased presentation of the trade-off between neonatal mobility and maternal reproductive risk?

Key Response

Counseling must balance the child's potential for independent ambulation and reduced shunt-related complications against maternal risks of PPROM, preterm birth, and lifelong uterine scarring. Practice-changing implications suggest this should only be offered at high-volume fetal centers where coordinated care between MFM, Neurosurgery, and Ethics committees is established.

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 (DSMB) due to efficacy. Discuss the potential for 'overestimation of effect' in early-stopped trials and how this might influence the statistical confidence in the long-term (30-month) neurodevelopmental secondary outcomes.

Key Response

Trials stopped early for benefit are susceptible to the 'Winner's Curse,' where the treatment effect size is often exaggerated. While the primary outcomes (shunting/motor function) were robust, the early termination may have limited the precision of secondary neurodevelopmental data, such as the Bayley Scales of Infant Development scores, requiring long-term follow-up studies like MOMS2.

Journal Editor
Journal Editor

Despite the randomized design, the MOMS trial could not be blinded for the surgical intervention. How does the use of an 'independent, blinded examiner' for the 12-month and 30-month assessments protect the internal validity of the study, and what threats to validity remain?

Key Response

Using blinded assessors for the primary outcomes (Bayley scores and Motor Function) minimizes observer bias, which is the greatest threat in unblinded trials. However, 'unblinding' can occur if the examiner notices the maternal surgical scar or if parents inadvertently reveal the treatment group, potentially introducing subtle bias in performance-based testing.

Guideline Committee
Guideline Committee

Based on the findings of the MOMS trial and subsequent ACOG/SMFM consensus, what are the absolute contraindications for prenatal repair that must be maintained in clinical guidelines to ensure maternal safety?

Key Response

Current guidelines (e.g., ACOG Committee Opinion No. 720) emphasize that prenatal repair should only be offered when the fetus has a normal karyotype, the mother has a BMI < 35, and there is no risk of preterm labor. These strict criteria are necessary because the maternal risks of surgery (pulmonary edema, placental abruption, and uterine rupture) are only justified when the likelihood of a successful fetal outcome is high and maternal complications can be managed.

Clinical Landscape

Noteworthy Related Trials

2014

Management of Myelomeningocele Study (MOMS) Follow-up

n = 183 · Obstet Gynecol

Tested

Prenatal myelomeningocele repair

Population

Children aged 30 months who participated in the original MOMS trial

Comparator

Postnatal repair

Endpoint

Neurodevelopmental and motor outcomes at 30 months

Key result: The benefits of prenatal surgery on motor function and the need for shunt placement persisted through 30 months of age.
2020

MOMS2 Trial

n = 208 · Pediatrics

Tested

Prenatal myelomeningocele repair

Population

Children who underwent prenatal repair in the original MOMS trial

Comparator

Children who underwent postnatal repair in the original MOMS trial

Endpoint

Motor and cognitive function at school age

Key result: At school age, prenatal repair did not show significant differences in cognitive or motor function compared to postnatal repair, though it remained associated with improved mobility outcomes.
2020

Fetoscopic vs Open MOMS Trial

n = 40 · Ultrasound Obstet Gynecol

Tested

Fetoscopic prenatal repair

Population

Fetuses with myelomeningocele

Comparator

Open prenatal repair

Endpoint

Maternal and fetal outcomes including shunt dependency

Key result: Fetoscopic repair was associated with reduced maternal morbidity and comparable fetal outcomes to open surgery.

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