Background

Previous reports from the Management of Myelomeningocele Study demonstrated that prenatal repair of myelomeningocele reduces hindbrain herniation and the need for cerebrospinal fluid shunting, and improves motor function in children with myelomeningocele. The trial was stopped for efficacy after 183 patients were randomized, but 30-month outcomes were only available at the time of initial publication in 134 mother-child dyads. Data from the complete cohort for the 30-month outcomes are presented here. Maternal and 12-month neurodevelopmental outcomes for the full cohort were reported previously.

Objective

The purpose of this study is to report the 30-month outcomes for the full cohort of patients randomized to either prenatal or postnatal repair of myelomeningocele in the original Management of Myelomeningocele Study.

Study design

Eligible women were randomly assigned to undergo standard postnatal repair or prenatal repair <26 weeks gestation. We evaluated a composite of mental development and motor function outcome at 30 months for all enrolled patients as well as independent ambulation and the Bayley Scales of Infant Development, Second Edition. We assessed whether there was a differential effect of prenatal surgery in subgroups defined by: fetal leg movements, ventricle size, presence of hindbrain herniation, gender, and location of the myelomeningocele lesion. Within the prenatal surgery group only, we evaluated these and other baseline parameters as predictors of 30-month motor and cognitive outcomes. We evaluated whether presence or absence of a shunt at 1 year was associated with 30-month motor outcomes.

Results

The data for the full cohort of 183 patients corroborate the original findings of Management of Myelomeningocele Study, confirming that prenatal repair improves the primary outcome composite score of mental development and motor function (199.4 ± 80.5 vs 166.7 ± 76.7, P = .004). Prenatal surgery also resulted in improvement in the secondary outcomes of independent ambulation (44.8% vs 23.9%, P = .004), WeeFIM self-care score (20.8 vs 19.0, P = .006), functional level at least 2 better than anatomic level (26.4% vs 11.4%, P = .02), and mean Bayley Scales of Infant Development, Second Edition, psychomotor development index (17.3% vs 15.1%, P = .03), but does not affect cognitive development at 30 months. On subgroup analysis, there was a nominally significant interaction between gender and surgery, with boys demonstrating better improvement in functional level and psychomotor development index. For patients receiving prenatal surgery, the presence of in utero ankle, knee, and hip movement, absence of a sac over the lesion and a myelomeningocele lesion of ≤L3 were significantly associated with independent ambulation. Postnatal motor function showed no correlation with either prenatal ventricular size or postnatal shunt placement.

Conclusion

The full cohort data of 30-month cognitive development and motor function outcomes validate in utero surgical repair as an effective treatment for fetuses with myelomeningocele. Current data suggest that outcomes related to the need for shunting should be counseled separately from the outcomes related to distal neurologic functioning.

BACKGROUND AND OBJECTIVES: The Management of Myelomeningocele Study (MOMS), a randomized trial of prenatal versus postnatal repair for myelomeningocele, found that prenatal surgery resulted in reduced hindbrain herniation and need for shunt diversion at 12 months of age and better motor function at 30 months. In this study, we compared adaptive behavior and other outcomes at school age (5.9-10.3 years) between prenatal versus postnatal surgery groups. METHODS: Follow-up cohort study of 161 children enrolled in MOMS. Assessments included neuropsychological and physical evaluations. Children were evaluated at a MOMS center or at a home visit by trained blinded examiners. RESULTS: The Vineland composite score was not different between surgery groups (89.0 ± 9.6 in the prenatal group versus 87.5 ± 12.0 in the postnatal group; P = .35). Children in the prenatal group walked without orthotics or assistive devices more often (29% vs 11%; P = .06), had higher mean percentage scores on the Functional Rehabilitation Evaluation of Sensori-Neurologic Outcomes (92 ± 9 vs 85 ± 18; P < .001), lower rates of hindbrain herniation (60% vs 87%; P < .001), had fewer shunts placed for hydrocephalus (49% vs 85%; P < .001) and, among those with shunts, fewer shunt revisions (47% vs 70%; P = .02) than those in the postnatal group. Parents of children repaired prenatally reported higher mean quality of life z scores (0.15 ± 0.67 vs 0.11 ± 0.73; P = .008) and lower mean family impact scores (32.5 ± 7.8 vs 37.0 ± 8.9; P = .002). CONCLUSIONS: There was no significant difference between surgery groups in overall adaptive behavior. Long-term benefits of prenatal surgery included improved mobility and independent functioning and fewer surgeries for shunt placement and revision, with no strong evidence of improved cognitive functioning.

Object

The Management of Myelomeningocele Study (MOMS) was a multicenter randomized trial comparing the safety and efficacy of prenatal and postnatal closure of myelomeningocele. The trial was stopped early because of the demonstrated efficacy of prenatal surgery, and outcomes on 158 of 183 pregnancies were reported. Here, the authors update the 1-year outcomes for the complete trial, analyze the primary and related outcomes, and evaluate whether specific prerandomization risk factors are associated with prenatal surgery benefit.

Methods

The primary outcome was a composite of fetal loss or any of the following: infant death, CSF shunt placement, or meeting the prespecified criteria for shunt placement. Primary outcome, actual shunt placement, and shunt revision rates for prenatal versus postnatal repair were compared. The shunt criteria were reassessed to determine which were most concordant with practice, and a new composite outcome was created from the primary outcome by replacing the original criteria for CSF shunt placement with the revised criteria. The authors used logistic regression to estimate whether there were interactions between the type of surgery and known prenatal risk factors (lesion level, gestational age, degree of hindbrain herniation, and ventricle size) for shunt placement, and to determine which factors were associated with shunting among those infants who underwent prenatal surgery.

Results

Ninety-one women were randomized to prenatal surgery and 92 to postnatal repair. The primary outcome occurred in 73% of infants in the prenatal surgery group and in 98% in the postnatal group (p < 0.0001). Actual rates of shunt placement were only 44% and 84% in the 2 groups, respectively (p < 0.0001). The authors revised the most commonly met criterion to require overt clinical signs of increased intracranial pressure, defined as split sutures, bulging fontanelle, or sunsetting eyes, in addition to increasing head circumference or hydrocephalus. Using these modified criteria, only 3 patients in each group met criteria but did not receive a shunt. For the revised composite outcome, there was a difference between the prenatal and postnatal surgery groups: 49.5% versus 87.0% (p < 0.0001). There was also a significant reduction in the number of children who had a shunt placed and then required a revision by 1 year of age in the prenatal group (15.4% vs 40.2%, relative risk 0.38 [95% CI 0.22-0.66]). In the prenatal surgery group, 20% of those with ventricle size < 10 mm at initial screening, 45.2% with ventricle size of 10 up to 15 mm, and 79.0% with ventricle size ≥ 15 mm received a shunt, whereas in the postnatal group, 79.4%, 86.0%, and 87.5%, respectively, received a shunt (p = 0.02). Lesion level and degree of hindbrain herniation appeared to have no effect on the eventual need for shunting (p = 0.19 and p = 0.13, respectively). Similar results were obtained for the revised outcome.

Conclusions

Larger ventricles at initial screening are associated with an increased need for shunting among those undergoing fetal surgery for myelomeningocele. During prenatal counseling, care should be exercised in recommending prenatal surgery when the ventricles are 15 mm or larger because prenatal surgery does not appear to improve outcome in this group. The revised criteria may be useful as guidelines for treating hydrocephalus in this group.

Background

The Management of Myelomeningocele Study was a multicenter, randomized controlled trial that compared prenatal repair with standard postnatal repair for fetal myelomeningocele.

Objective

We sought to describe the long-term impact on the families of the women who participated and to evaluate how the timing of repair influenced the impact on families and parental stress.

Study design

Randomized women completed the 24-item Impact on Family Scale and the 36-item Parenting Stress Index Short Form at 12 and 30 months after delivery. A revised 15-item Impact on Family Scale describing overall impact was also computed. Higher scores reflected more negative impacts or greater stress. In addition, we examined Family Support Scale and Family Resource Scale scores along with various neonatal outcomes. Repeated measures analysis was conducted for each scale and subscale.

Results

Of 183 women randomized, 171 women completed the Impact on Family Scale and 172 completed the Parenting Stress Index at both 12 and 30 months. The prenatal surgery group had significantly lower revised 15-item Impact on Family Scale scores as well as familial-social impact subscale scores compared to the postnatal surgery group (P = .02 and .004, respectively). There was no difference in total parental stress between the 2 groups (P = .89) or in any of the Parenting Stress Index Short Form subscales. In addition, walking independently at 30 months and family resources at 12 months were associated with both family impact and parental stress.

Conclusion

The overall negative family impact of caring for a child with spina bifida, up to 30 months of age, was significantly lower in the prenatal surgery group compared to the postnatal surgery group. Ambulation status and family resources were predictive of impact on family and parental stress.

Background

The Management of Myelomeningocele Study was a multicenter randomized trial to compare prenatal and standard postnatal closure of myelomeningocele. The trial was stopped early at recommendation of the data and safety monitoring committee and outcome data for 158 of the 183 randomized women published.

Objective

In this report, pregnancy outcomes for the complete trial cohort are presented. We also sought to analyze risk factors for adverse pregnancy outcome among those women who underwent prenatal myelomeningocele repair.

Study design

Pregnancy outcomes were compared between the 2 surgery groups. For women who underwent prenatal surgery, antecedent demographic, surgical, and pregnancy complication risk factors were evaluated for the following outcomes: premature spontaneous membrane rupture ≤34 weeks 0 days (preterm premature rupture of membranes), spontaneous membrane rupture at any gestational age, preterm delivery at ≤34 weeks 0 days, nonintact hysterotomy (minimal uterine wall tissue between fetal membranes and uterine serosa, or partial or complete dehiscence at delivery), and chorioamniotic membrane separation. Risk factors were evaluated using χ² and Wilcoxon tests and multivariable logistic regression.

Results

A total of 183 women were randomized: 91 to prenatal and 92 to postnatal surgery groups. Analysis of the complete cohort confirmed initial findings: that prenatal surgery was associated with an increased risk for membrane separation, oligohydramnios, spontaneous membrane rupture, spontaneous onset of labor, and earlier gestational age at birth. In multivariable logistic regression of the prenatal surgery group adjusting for clinical center, earlier gestational age at surgery and chorioamniotic membrane separation were associated with increased risk of spontaneous membrane rupture (odds ratio, 1.49; 95% confidence interval, 1.01-2.22; and odds ratio, 2.96, 95% confidence interval, 1.05-8.35, respectively). Oligohydramnios was associated with an increased risk of subsequent preterm delivery (odds ratio, 9.21; 95% confidence interval, 2.19-38.78). Nulliparity was a risk factor for nonintact hysterotomy (odds ratio, 3.68; 95% confidence interval, 1.35-10.05).

Conclusion

Despite the confirmed benefits of prenatal surgery, considerable maternal and fetal risk exists compared with postnatal repair. Early gestational age at surgery and development of chorioamniotic membrane separation are risk factors for ruptured membranes. Oligohydramnios is a risk factor for preterm delivery and nulliparity is a risk factor for nonintact hysterotomy at delivery.

Background

A substudy of the Management of Myelomeningocele Study evaluating urological outcomes was conducted.

Methods

Pregnant women diagnosed with fetal myelomeningocele were randomly assigned to either prenatal or standard postnatal surgical repair. The substudy included patients randomly assigned after April 18, 2005. The primary outcome was defined in their children as death or the need for clean intermittent catheterization (CIC) by 30 months of age characterized by prespecified criteria. Secondary outcomes included bladder and kidney abnormalities observed by urodynamics and renal/bladder ultrasound at 12 and 30 months, which were analyzed as repeated measures.

Results

Of the 115 women enrolled in the substudy, the primary outcome occurred in 52% of children in the prenatal surgery group and 66% in the postnatal surgery group (relative risk [RR]: 0.78; 95% confidence interval [CI]: 0.57-1.07). Actual rates of CIC use were 38% and 51% in the prenatal and postnatal surgery groups, respectively (RR: 0.74; 95% CI: 0.48-1.12). Prenatal surgery resulted in less trabeculation (RR: 0.39; 95% CI: 0.19-0.79) and fewer cases of open bladder neck on urodynamics (RR: 0.61; 95% CI: 0.40-0.92) after adjustment by child's gender and lesion level. The difference in trabeculation was confirmed by ultrasound.

Conclusions

Prenatal surgery did not significantly reduce the need for CIC by 30 months of age but was associated with less bladder trabeculation and open bladder neck. The implications of these findings are unclear now, but support the need for long-term urologic follow-up of patients with myelomeningocele regardless of type of surgical repair.

The Management of Myelomeningocele Study (MOMS), a randomized trial of prenatal versus postnatal repair for myelomeningocele, found that prenatal surgery resulted in reduced hindbrain herniation and need for shunt diversion at 12 months of age and better motor function at 30 months. In this study, we compared adaptive behavior and other outcomes at school age (5.9-10.3 years) between prenatal versus postnatal surgery groups. Follow-up cohort study of 161 children enrolled in MOMS. Assessments included neuropsychological and physical evaluations. Children were evaluated at a MOMS center or at a home visit by trained blinded examiners. The Vineland composite score was not different between surgery groups (89.0 ± 9.6 in the prenatal group versus 87.5 ± 12.0 in the postnatal group; P = .35). Children in the prenatal group walked without orthotics or assistive devices more often (29% vs 11%; P = .06), had higher mean percentage scores on the Functional Rehabilitation Evaluation of Sensori-Neurologic Outcomes (92 ± 9 vs 85 ± 18; P < .001), lower rates of hindbrain herniation (60% vs 87%; P < .001), had fewer shunts placed for hydrocephalus (49% vs 85%; P < .001) and, among those with shunts, fewer shunt revisions (47% vs 70%; P = .02) than those in the postnatal group. Parents of children repaired prenatally reported higher mean quality of life z scores (0.15 ± 0.67 vs 0.11 ± 0.73; P = .008) and lower mean family impact scores (32.5 ± 7.8 vs 37.0 ± 8.9; P = .002). There was no significant difference between surgery groups in overall adaptive behavior. Long-term benefits of prenatal surgery included improved mobility and independent functioning and fewer surgeries for shunt placement and revision, with no strong evidence of improved cognitive functioning.