Neurodevelopmental outcome of children with spina bifida aperta repaired prenatally vs postnatally: systematic review and meta‐analysis

Abstract

Objective To assess the neurodevelopmental outcome of children with spina bifida aperta (SBA) treated prenatally as compared to those treated postnatally. Methods We performed a systematic review of the literature in PubMed/MEDLINE, EMBASE, Web of Science and The Cochrane Library, comparing the neurological outcome of infants with SBA treated prenatally vs postnatally. Only randomized controlled trials (RCTs) and non‐randomized prospective controlled studies were included. The primary outcome assessed was neurodevelopmental impairment at the age of 1 year or later. Secondary outcomes were preterm birth, need for ventriculoperitoneal (VP) shunt by 12 months of age, absence of signs of hindbrain herniation at the first postnatal magnetic resonance imaging (MRI) evaluation and independent ambulation evaluated at 30 months. Results Of 11 359 studies identified through the electronic search, six met the inclusion criteria and were assessed in full text and two, one RCT and one prospective cohort study, were ultimately included in the meta‐analysis. Sensitivity analysis did not show any difference between the outcomes of the RCT alone and those of the pooled RCT and prospective cohort study. This allowed neurodevelopmental assessment of 213 children between 14 and 53 months of age. Neurodevelopment was assessed by the Bayley Scales of Infant Development II (BSID‐II) mental development index corrected for chronological age, with a cut‐off of ≥ 70 (representing no more than 2 SD below the mean). The presence of neurodevelopmental impairment was similar between children who underwent prenatal (25/105 (23.8%)) and those who had postnatal (30/108 (27.8%)) repair of SBA (odds ratio (OR), 0.82 (95% CI, 0.43–1.56); P = 0.54), although the risk of prematurity was higher in the prenatal‐repair group (OR, 17.62 (95% CI, 7.60–40.87); P < 0.0001). For every two fetuses operated on before birth, there was, compared with those operated on after birth, one additional premature birth (number needed to harm = 2 (95% CI, 1–3)). The need for VP shunt placement by 12 months of age was lower in the prenatal‐repair group (45/109 (41.3%)) than in children that had postnatal repair (93/112 (83.0%); OR, 0.14 (95% CI, 0.08–0.26); P < 0.0001). Data on neurodevelopmental impairment in children with a shunt were available only for patients from the prenatal‐surgery group of the RCT; in this subgroup, the likelihood for impairment was similar between children who did (7/39 (17.9%)) and those who did not (4/48 (8.3%)) have shunt placement (P = 0.21). At first postnatal MRI evaluation, no signs of hindbrain herniation were detected in 28/88 (31.8%) children who were operated on prenatally compared with 4/89 (4.5%) who had postnatal repair (OR, 9.45 (95% CI, 3.12–28.64); P < 0.0001). Independent ambulation at 30 months was achieved by 41/109 (37.6%) children who underwent prenatal repair compared with 21/111 (18.9%) who had postnatal repair (OR, 2.59 (95% CI, 1.39–4.86); P = 0.003). Conclusion The risk of neurodevelopmental impairment in infan...

Management of prenatally diagnosed spina bifida: how do we move ahead?

“…The forest plots in this systematic review underscore that the addition of the prospective cohort study did little to improve on the results from the MOMS trial. The only confidence interval that was significantly narrowed by the combination of the two studies was that for absence of signs of hindbrain herniation.…”

“…The first is a systematic review and meta‐analysis, which, by definition, should avoid the pitfalls associated with single‐study evidence. From the systematic review process, we hope to determine the best clinical practice based on the synthesized evidence.…”

“…From a methodological perspective, the systematic review by Inversetti et al . was conducted beautifully, incorporating all of the requisite checks and balances.…”

“…While the selection criteria for this systematic review included both open and less invasive fetal surgical approaches, the two included studies had performed only open surgery for prenatal repair. If we wish to evaluate effectively minimally invasive techniques, simply publishing results from a cohort undergoing such procedures will be insufficient to prove benefit.…”

“…While Inversetti et al . 's systematic review was a stellar undertaking, with only two studies ultimately meeting the selection criteria for a meta‐analysis, are there really sufficient data with which to proceed? There is no definitive guidance on the number of studies that are necessary for a meta‐analysis.…”