Prenatal Myelomeningocele Repair Improves Outcomes: The MOMS Trial

Megan Brooks

February 09, 2011

February 9, 2011 — Repairing a myelomeningocele in utero, rather than after birth, reduces the risk for fetal or neonatal death and the need for shunting by age 1 and substantially improves neurologic and motor outcomes. However, it is not without maternal and fetal risks.

These are the findings, in a nutshell, of the long-awaited Management of Myelomeningocele Study (MOMS), which were published online February 9 in The New England Journal of Medicine.

The study was led by N. Scott Adzick, MD, Surgeon-in-Chief and Director of the Center for Fetal Diagnosis and Treatment at The Children's Hospital of Philadelphia, an early pioneer of prenatal myelomeningocele repair.

Dr. N. Scott Adzick

"Both the experimental outcomes of animal studies and the results of the MOMS trial suggest that prenatal surgery for myelomeningocele stops the exposure of the developing spinal cord to amniotic fluid and thereby averts further neurological damage in utero," Dr. Adzick said in a statement.

"In addition, by stopping the leak of cerebrospinal fluid from the myelomeningocele defect, prenatal surgery reverses hindbrain herniation in utero. We believe this in turn mitigates the development of hydrocephalus and the need for shunting after birth."

Joe Leigh Simpson, MD, of Florida International University in Miami, and Michael F. Greene, MD, of Massachusetts General Hospital in Boston, authors of an accompanying editorial, note that postnatal repair of myelomeningocele is associated with "less-than-desirable" long-term neurologic outcome. While the degree to which intrauterine repair will "transform outcomes for fetuses with myelomeningocele remains unclear," the MOMS trial is "a major step in the right direction," they write.

The MOMS Trial

Spina bifida is the most common congenital anomaly of the central nervous system and myelomeningocele is the most frequent form, occurring in an estimated 3.4 of every 10,000 live births in the United States. Myelomeningocele is characterized by the extrusion of the spinal cord into a sac filled with cerebrospinal fluid, resulting in lifelong disability.

The MOMS trial assessed outcomes of prenatal surgery (through the use of hysterotomy and open fetal repair) as compared with standard postnatal repair. The study involved nonobese women in good health with singleton pregnancy, an isolated myelomeningocele located between T1 and S1, evidence of hindbrain herniation on fetal magnetic resonance imaging, and a normal karyotype.

Fetus with myelomeningocele before (left) and after (right) surgical repair. The Center for Fetal Diagnosis and Treatment at Children’s Hospital of Philadelphia

From February 2003 through December 2010, 183 of 1233 screened women (15%) were randomly assigned to prenatal surgery performed at 19 to 26 weeks of gestation, followed by planned cesarean delivery at 37 weeks, or to postnatal surgery, usually within 24 hours after cesarean delivery at 37 weeks' gestation.

The goal was to enroll 200 women, but the trial was halted early in December 2010 after 183 surgeries had occurred. Discontinuation was based on clear evidence of efficacy in the prenatal surgery group, the researchers report. Outcomes at 12 months and 30 months are based on 158 and 134 women, respectively.

"In the big view," Dr. Adzick told Medscape Medical News, "the operation before birth reduced the need for ventricular shunting to treat hydrocephalus and improved motor outcomes at 30 months of age, so more kids in the fetal surgery group could walk, basically."

The findings were "quite striking," he added.

In the intention-to-treat analysis, the first primary outcome — fetal or neonatal death or the need for a cerebrospinal fluid shunt by 12 months — occurred in 68% of infants in the prenatal surgery group vs 98% in the postnatal surgery group, a relative risk reduction of 30% (relative risk, 0.70; 95% confidence interval [CI], 0.58 - 0.85; P < .001).

Actual rates of shunt placement at 12 months of age were 40% and 82%, respectively, yielding a relative risk reduction of 52% with prenatal surgery (relative risk, 0.48; 97.7% CI, 0.36 - 0.64; P < .001).

At 12 months, the proportion of infants with no evidence of hindbrain herniation was higher in the prenatal than the postnatal surgery group (36% vs 4%) and the rate of moderate or severe hindbrain herniation was lower (25% vs 67%).

At 30 months, prenatal surgery relative to postnatal surgery also resulted in a significant improvement in the composite score for mental development (Bayley Mental Development Index) and motor function (P = .007). Forty-two percent of children in the prenatal surgery group were able to walk independently without orthotics or devices vs 21% of children in the postnatal surgery group (P = .01).

Dr. Adzick and his colleagues note in their report that although the prenatal surgery group had better outcomes than the postnatal surgery group, "not all infants benefited from the early intervention, and some had a poor neuromotor outcome." Going forward, "we need to refine things in terms of diagnosis and figuring out which fetuses with spina bifida will benefit the most," Dr. Adzick told Medscape Medical News.

Risk-Benefit Counseling Crucial

The investigators also emphasize that the "potential benefits of prenatal surgery must be balanced against the risks."

Prenatal surgery was associated with higher rates of maternal and certain fetal complications, including spontaneous membrane rupture (46% vs 8%), oligohydramnios (21% vs 4%), preterm birth (79% vs 15%), and more complications associated with prematurity, such as respiratory distress syndrome, which was seen in one fifth of infants in the prenatal surgery group. One third of women who underwent prenatal surgery had an area of dehiscence or a very thin prenatal uterine surgery scar at the hysterotomy site.

In their commentary, Dr. Simpson and Dr. Greene emphasize the need for explicit risk-benefit conversations with women contemplating prenatal myelomeningocele repair.

"For many women, the 20% absolute improvement in ambulation at the age of 3 years and the decreased need for shunting may be perceived as sufficient to justify the increased risk of maternal complications, but it should be recognized that outcomes after prenatal surgery were less than perfect in MOMS."

They further note that couples may "unavoidably feel pressured 'to do everything possible' and hence may be inclined to interpret even marginal benefit favorably. It is also human nature to overestimate the likely benefit for one's own fetus and to underestimate the associated risks."

Drs. Simpson and Greene encourage clinicians to give precise quantitative comparative information on prenatal vs postnatal surgery on the basis of the MOMS trial, as well as information on center-specific experience with the surgery.

Regionalization?

For the duration of the MOMS trial, all cases of myelomeningocele were funneled to the 3 study centers: The Children’s Hospital of Philadelphia, Vanderbilt University, and the University of California San Francisco. All other US fetal surgery centers not participating in the trial agreed not to perform fetal surgery for spina bifida during the 7-year duration of the trial.

On the basis of the now-published trial results, other US centers are likely to initiate their own programs; "fetal results may not be as good as those in MOMS and maternal complications could be increased," the editorialists warn.

Dr. Adzick and colleagues agree that the MOMS trial results should not be generalized to patients who have the surgery at less experienced centers or who do not meet the eligibility criteria. The surgery "really requires an expert multidisciplinary team," Dr. Adzick said; he thinks it should be "strongly regionalized."

The MOMS trial was sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, part of the National Institutes of Health. A complete list of disclosures for study authors and editorialists can be found with the original articles.

N Engl J Med. Published online February 9, 2011.

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