A comparison of prenatal and postnatal repair of myelomeningocele: a systematic review and meta- analysis

A comparison of prenatal and postnatal repair of myelomeningocele: a systematic review and meta- analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article A comparison of prenatal and postnatal repair of myelomeningocele: a systematic review and meta- analysis Arooba Ishmal, Hamid Rehman, Manav Das, Imad Khan, Laiba Zaman, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7216514/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Myelomeningocele (MMC), the most severe form of spina bifida, is associated with lifelong disability due to incomplete neural tube closure. Traditionally repaired postnatally, prenatal surgical intervention has emerged as a promising alternative, potentially preventing neurological deterioration. This meta-analysis aimed to compare prenatal and postnatal surgical repair of MMC in terms of motor function, ambulation, shunt dependency, and mortality. Methods: A comprehensive search of PubMed, Scopus, and Cochrane databases was conducted through May 2025. Eligible studies included randomized controlled trials and cohort studies comparing prenatal and postnatal MMC repair. Primary outcomes were motor function and walking independence. Secondary outcomes included ventriculoperitoneal (VP) shunt placement and neonatal mortality. Risk of bias was assessed using the Cochrane RoB2 and Newcastle–Ottawa Scale. Results: Four studies (N=516 patients) met inclusion criteria. Prenatal repair significantly improved functional mobility (RR = 2.45, 95% CI: 1.72–3.47, p < 0.00001, I² = 0%) and walking independence (RR = 2.33, 95% CI: 1.52–3.55, p < 0.0001, I² = 13%). A trend toward reduced VP shunt placement was observed in the prenatal group (RR = 0.52, p = 0.06), though not statistically significant. Mortality was slightly higher in the prenatal group (RR = 1.49, p = 0.48), but without significance. Conclusion: Prenatal MMC repair yields superior motor outcomes and greater walking independence without significantly affecting mortality. While shunt dependency may be reduced, further research is required to confirm long-term safety and optimize patient selection. Prenatal surgery should be considered in specialized centers with multidisciplinary expertise. Myelomeningocele Prenatal Surgery Postnatal Repair Motor Function Systematic Review Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Myelomeningocele (MMC) is the most common congenital defect of the central nervous system, resulting from incomplete neural tube closure early in gestation, typically within the first 6 weeks, leading to significant lifelong disabilities. 1 , 2 The approximate incidence of myelomeningocele (MM) in the United States is 3.4 per 10, 000 live births. 3 Live-born infants with MM have an approximately 10% risk of mortality, and survivors face significant morbidity. Conventional treatment of MM has been to perform a postnatal repair within 48 hours after birth. After repair of the defect, neurosurgeons must remain vigilant about recognizing and treating hydrocephalus, which is a frequent comorbidity in MM patients. 4 The NIH-sponsored Management of Myelomeningocele Study (MOMS) was initiated in 2003 to compare the safety and efficacy of prenatal repair of myelomeningocele with that of standard postnatal repair. The trial was stopped in 2010 before reaching the target sample size, at the recommendation of its Data and Safety Monitoring Committee (DSMC), in accordance with the stopping rules for the efficacy of prenatal surgery. 5 Results of the trial were reported based on 158 women who had undergone randomization before July 1, 2009, as this was the cohort analyzed for the DSMC. Findings in that report demonstrated a significant improvement in the primary outcomes at 12 and 30 months of age, and in multiple secondary outcomes, including reversal of hindbrain herniation and ambulation by 30 months, in the prenatal repair group. 6 Sequential ultrasonographic images that are obtained from fetuses with myelomeningocele suggest that insults to both the central and peripheral nervous systems may be progressive. Movement in the lower limbs may be lost, and hindbrain herniation and hydrocephalus may worsen during fetal gestation. 7 , 8 , 9 Historically, myelomeningocele has been managed with surgical repair after birth. However, prenatal (in utero) repair has emerged as an alternative that may prevent progression of neurologic damage caused by prolonged exposure of neural tissue to amniotic fluid and mechanical trauma. However, it also carries risks such as preterm birth and maternal morbidity. 10 Taking all the above into account, the main aim of this systematic review and meta-analysis was to compare Motor function in patients following treatment of myelomeningocele through postnatal vs prenatal surgical repair, as assessed by Walking status (independent vs assisted), Peabody Developmental Motor Scales (PDMS-2) gross motor score or any other validated criteria. This review will gather global evidence to answer: Which approach truly gives babies and families the best shot at a healthier future? Existing reviews lack synthesis of recent evidence, long-term neurological outcomes, and maternal morbidity, creating clinical uncertainty. This meta-analysis addresses gaps by comparing prenatal vs. postnatal repair across diverse outcomes (mobility, ambulation, shunt rates, mortality), providing updated insights for risk-benefit counseling. Methodology Data sources and search strategy : This meta-analysis was conducted conclusively with the Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. 11 A comprehensive electronic search of PubMed (Medline), Sci-Hub Scopus, and Cochrane Central databases was conducted from inception to MAY 2025.. The following search terms were used: (Meningomyelocele OR ""Meningomyelocele""[Mesh])) AND (Postnatal) AND (Prenatal) AND (Mortality OR post-operative complications OR treatment outcomes OR ""Postoperative Complications""[Mesh] OR ""Mortality""[Mesh] OR ""Treatment Outcome""[Mesh])" Two unbiased authors (LZ and MD) searched without limitations or conflicts of interest. A search was conducted for relevant published or unpublished clinical trials. Furthermore, we conducted a search of the reference lists of the included research, as well as related meta-analyses and review articles, to identify possibly relevant studies. Study Selection : The eligibility criteria were Randomized controlled trials (RCTs) and Cohorts, with a target population of fetus or neonates diagnosed with Myelomeningocele (MMC). All studies had participants with singleton pregnancies where the MMC lesions were located between thoracic level t1 and sacral level s1 with evidence of hind brain herniation, involving postnatal repair compared with prenatal repair for myelomeningocele. We excluded review articles, protocols, uncontrolled trials, and observational studies other than cohort studies (e.g., case-control and cross-sectional designs). Additionally, commentaries, letters to the editor, and case reports were excluded. “The study selection process is depicted in the PRISMA 2020 flow diagram Data Extraction and Assessment of Study Quality : Duplicate studies were removed from the list after exporting the retrieved articles to Endnote Reference Library Software. All data extracted from the included studies during this systematic review and meta-analysis are available from the corresponding author upon reasonable request. Two reviewers (LZ AND MD) then carefully assessed the remaining articles, and only those that met the previously stated eligibility conditions were included. All the articles were first screened based on the abstract and title. After that, the remaining articles were screened through the full text. A third reviewer (AI) was consulted to resolve any disagreements regarding the results. An online Microsoft Excel spreadsheet was created using data from the completed studies for the baseline characteristics and outcomes. Baseline parameters are as follows: Maternal age, Maternal BMI, presence of chiari II malformation, Prevalence of Hydrocephalus, Hind brain herniation severity. These outcomes were included: Primary Outcomes : Motor function at 30 months Ambulation status SECONDARY OUTCOMES : Ventriculoperitoneal shunt (VP) shunt placement Neonatal Mortality The modified Cochrane Collaboration risk of bias technique was utilized to check the reliability of the included studies. Quality assessment and risk of bias were independently assessed using the Cochrane Risk of Bias Tool 2 for the randomized controlled trial, and the Newcastle–Ottawa Scale (NOS) for the cohort studies, by two investigators. The results were matched, and any discrepancies were resolved by team consensus. Meta-analysis : This meta-analysis used Review Manager (version 5.4. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Forest plots were generated for the results' visual display. The outcomes were displayed as risk ratios (RR) with a 95% confidence interval using the random effects model. Statistical heterogeneity was assessed using the I 2 Statistics, with values greater than 50% considered indicative of substantial heterogeneity among the 4 included studies. Results Study selection : The searches yielded 42 articles from PubMed and Cochrane Central databases. After filtering duplicates and excluding irrelevant articles based on title, 11 articles were examined for the availability of full texts and data related to the research objective. Following the assessment of complete texts, 4 articles were included for analysis. 12 , 13 , 14 , 15 The study selection steps are presented in Fig. 1 . Characteristics of studies : All four of the included articles compared outcomes of patients undergoing pre-natal vs post-natal surgical repair for myelomeningocele. Detailed characteristics of the included studies and the results of each study are outlined in Table 1 (Baseline Characteristics). The study by Diane L. Farmer et al. was a randomized control trial (2020) was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Clinical and Translational Science Awards, National Institutes of Health. 12 The study by Jacek Zamłyn´ ski et al. was a non-randomized, single center study conducted in Poland where screening for MMC occurred between 2005 and 2011 by tertiary perinatal centers and laboratories of prenatal diagnosis with FMF certification. 14 M. Sanz Cortez et al. conducted a retrospective review of a cohort of children who underwent open neural defect repair between November 2011 and May 2023. 15 The 2023 study by Anita L. Kalluri presented a retrospective review of all patients who underwent MMC repair between 2012 and 2022 at a single pediatric neurological tertiary care center. 13 Table 1 Baseline Characteristics Study Anita L. Kalluri Jacek Zamłynski M. Sanz Cortes Diana L. Farmer Population fetuses or neonates diagnosed with myelomeningocele (MMC) fetuses or neonates diagnosed with myelomeningocele (MMC) fetuses or neonates diagnosed with myelomeningocele (MMC) fetuses or neonates diagnosed with myelomeningocele (MMC) Intervention Prenatal repair for myelomeningocele Prenatal repair for myelomeningocele Prenatal repair for myelomeningocele Prenatal repair for myelomeningocele Control Postnatal repair for myelomeningocele Postnatal repair for myelomeningocele Postnatal repair for myelomeningocele Postnatal repair for myelomeningocele Study design Cohort Cohort Cohort RCT Total number of patients 79 patients 93 patients 161 patients 183 patients Maternal Age (years) Intervention 29 ± 5 28 (19–45) 29.2 ± 5.2 Maternal Age (years) control 27 ± 5 27 (17–24) 28.7 ± 4.8 Maternal BMI (kg/m²) Intervention 24.1 ± 3.2 25.8 (18.5–37.9) Maternal BMI (kg/m²) Control 26.7 ± 3.8 30.4 (17.9–60.0) Hindbrain Herniation: I – Small intervention 3(6.5%) Hindbrain Herniation: I – Small control 2 (4.3%) Hindbrain Herniation: II – Mild intervention 43 (93.5%) Hindbrain Herniation: severe intervention 0 27(29.7) Hindbrain Herniation: severe control 23 (25.0) Lesion Level Intervention 29 (96.7%) 100% Lesion Level control 41 (89.1%) 97.5% Lesion Level_2 Intervention 1 (3.3%) 84(76.4%) Lesion Level_2 Control 5 (10.9%) 40(78.4%) Thoracic Level Involved Intervention 1 (3.3%) 0 Thoracic Level Involved Control 5 (10.9%) 0 Lumbar Level Involved Intervention 30 (100.0%) 35(87.5%) Lumbar Level Involved control 46 (100.0%) 31(79.5%) Sacral Level Involved Intervention 29 (96.7%) 5(12.5%) 83.6% Sacral Level Involved Control 41 (89.1%) 7(17.9%) 72.0% Chiari 2 Malformation Intervention 29 (96.7%) 93.5% Chiari 2 Malformation control 41 (87.2%) 95.7% Hydrocephalus Intervention 15(50.0%) 37(33.6%) Hydrocephalus Control 28(59.6%) 40(78.4%) Foot Deformity Intervention 10(33.3%) 2(4.3%) 23(20.9%) 24(26.4) Foot Deformity Control 20(40.8%) 3(6.4%) 17(33.3%) 19(20.7) Corpus Callosum Agenesis, n (%) Intervention group 8(17.4) 8 (17.4%) Yes: 90 (99%) Corpus Callosum Agenesis, n (%) Control group 9(19.1) 9 (19.1%) NO: 1 (1%) Female fetal sex Intervention group 19 (63%) 23(50.0%) (0.61) 42(46.2) Female fetal sex Control group 28 (57.1%) 29(61.7%) 27(52.9) 57(62.0) Intact Motor At Birth (WALKING DEPENDENTLY) 9(50.0%) 32(60.4) Intact Motor At Birth (WALKING INDEPENDENTLY) 2(11.1%) 50(87.7%) Risk of bias assessment : The quality of individual studies analysis was conducted according to the study design using Cochrane Risk of Bias Tool 2, 16 for the randomized controlled trial, where this checklist was used to analyze the risk of bias in the studies. The results of the risk of bias assessment are presented in supplementary Fig. 1. The Newcastle–Ottawa Scale (NOS) 17 was used for quality assessment of the cohort studies, the results are presented in supplementary table 1 . PRIMARY OUTCOMES : Figure 2 shows the forest plot comparing functional mobility in prenatal vs postnatal group. The functional mobility in the study by Anita L. Kalluri and M. Sanz Cortez was assessed at 12 months of age, while the Diane L. farmer study was assessed at 30 months through the Bayley Scales of Infant and Toddler Development (BSID) II psychomotor development index, and the score of ≥ 85 was taken as a marker for normal motor function. The pooled analysis shows a risk ratio (RR) of 2.45 (95% CI: 1.72–3.47) which shows that prenatal repair of myelomeningocele is associated with better motor function compared to post-natal repair. The p value (P < 0.00001) suggests the difference is statistically significant and the heterogeneity I² = 0% indicates consistency of results across the studies. Figure 3 compares the outcomes of independent ambulation in prenatal vs postnatal repair group. The pooled analysis shows a risk ratio of 2.33 (95% CI: 1.52–3.55) which indicates that infants who have undergone prenatal repair of myelomeningocele are 2.33 times more likely to walk independently than those who have undergone postnatal repair. The p value of less than 0.0001 indicates that the results are statistically significant and the relatively low heterogeneity demonstrates consistency of results across studies. SECONDARY OUTCOMES : Figure 4 represents a forest plot comparing the placement of ventriculoperitoneal (VP) shunt in patients after prenatal surgery for repair of myelomeningocele vs postnatal surgery. The risk ratio of 0.52 (95% CI: 0.26–1.02) indicates the risk of VP shunt placement was lower in prenatal group. The p value is 0.06 which suggesting a strong trend toward benefit with prenatal intervention that does not reach the threshold for significance. The heterogeneity is relatively high (I² = 69%) indicating significant variations across the studies. The forest plot in Fig. 5 compares the outcomes of mortality between the prenatal and the postnatal repair of myelomeningocele. The pooled analysis shows a risk ratio of 1.49 (95% CI: 0.49–4.51) indicating that the prenatal group is associated with higher rates of mortality than the postnatal group, however the p value (P = 0.48) suggests that the results are not statistically significant, hence the result is inconclusive. The very low heterogeneity I² = 3% indicates consistency of results across the studies. Publication Bias : Since there are fewer studies (4), we could not make funnel plots and perform Egger's regression test for accessing publication bias. Uncertainty of Evidence : The summary of findings table shows the evidence on the effect of prenatal surgical repair for myelomeningocele compared to postnatal repair. According to moderate certainty evidence prenatal repair likely improves walking independence and functional mobility. However, it may also increase mortality according to low certainty evidence. Furthermore, the need for VP shunt placement is uncertain due to very low certainty evidence (Supplementary Table 2). Discussion This meta-analysis is a modern and thorough review that compares the effectiveness of prenatal and postnatal surgical repair of myelomeningocele (MCC) regarding important outcomes such as mobility, independent walking, ventriculoperitoneal (VP) shunt placement, and death. The incorporation of recent RCTs and prospective studies into this analysis provides a more detailed view of the functional and neurological advantages, as well as the limitations and risks, of prenatal surgery. There was a statistically significant improvement of functional mobility in prenatal repair favor. In three randomized controlled trials (380 participants; 208 prenatal and 172 postnatal), prenatal repair turned the probability of having an improvement of functional mobility, with an overall risk ratio (RR) of 2.45 (95% CI: 1.72–3.47; p < 0.00001), and no heterogeneity (I² = 0). These data support the previous ones that were provided by the landmark MOMS trial and its follow-ups which confirmed better motor performances at 30 months of age in the prenatal group than in the postnatal group. 9 , 18 Danzer et al. (2020) showed better lower limbs functioning among patients having prenatal repair, and Sanz-Cortes et al. (2024) mentioned the success of fetoscopic procedures in relation to motor functioning. 15 , 19 Regarding walking independence, 3 studies and 374 participants (215 prenatal, 159 postnatal) showed that prenatal surgery had a significant impact on ambulation outcomes (RR = 2.33, 95% CI: 1.52–3.55; p < 0.0001, I² = 13%). The result concurs with other previous findings by MOMS trial who recorded increased ambulation in the prenatal group. 9 The uniformity of research studies indicates that the prenatal repair may provide factual functional benefit, possibly by spinal cord protection. In terms of VP shunt placement, the data of 291 persons (134 prenatal, 157 postnatal) indicates that prenatal surgery can reduce the threat due to a 48 percent probability (RR = 0.52, 95% CI: 0.26–1.02; p = 0.06), but it failed to be statistically significant. The level of heterogeneity was moderate (I² = 69%), which may indicate indifferences in used criteria of shunts and institutional guidelines. However, this correlates with previous reports that were expressed with reduced frequency of hydrocephalus and hindbrain herniation in the prenatal cohort. 9 , 15 In a similar fashion, Moldenhauer et al. (2015) and Kernaghan D, Mauer E, Farmer DL, et al. reported lower levels of shunt dependency in patients of the prenatal cohort. 18 , 16 Lastly in case of mortality, results of four studies indicated that there is no statistically significant modification between the prenatal and postnatal repair groups (RR = 1.44, 95% CI: 0.50–4.13; p = 0.49), with low heterogeneity (I² = 1%). One would think that the point estimate reflects the higher mortality rates in the prenatal community, but it is not statistically so. The safety of prenatal surgery, which has been reported previously and by the MOMS trial as well as Zamelinski et al. (2014), has been confirmed by previous reports. 9 , 18 Nonetheless, the risk of experience to mothers, e.g., uterine rupture, chorioamniotic separation, preterm premature rupture of membranes, etc. is still not trivial, particularly when it is open fetal surgery 14 , 15 . Those of these maternal risks can be alleviated with some of the emerging techniques such as fetoscopic repair. 15 Notwithstanding such positive results, the presented meta-analysis has its limitations. The available studies are also insufficient and do not allow subgroup and sensitivity analyses to be robust. Heterogeneity in the methods used during surgery, postoperative treatment and standards of determining the outcomes evaluation also exists, especially in VP shunt placement results. Moreover, the follow-up times of the majority of the studies are inadequate to fully report neurodevelopmental, educational, and psychosocial results in adults. In what is frequently put in force during functional assessments, parental reporting creates bias subjectivity. There are a few strengths of this meta-analysis. First, it comprises a restricted set of randomized control trials (RCTs) and prospective studies that have the utmost support in terms of clinical evidence. Recent studies have been included to provide the synthesis of the recent studies of prenatal versus postnatal repair outcomes in myelomeningocele (MMC). Functional mobility, the need for VP shunt, independent ambulation and mortality were reported with clear outcome measures across information and these improvements made comparability and internal validity. Second, the study used thorough methodology in the analysis and used PRISMA method of analysis, clear selection criteria, and a strong statistical synthesis with tests of heterogeneity. Regarding the major results such as walking independence and functional mobility, the heterogeneity was zero (I²: 0%), which means that the studies included comparable results, and the findings added in the background led to a higher probability of accurate results. Future studies must focus on the long term senescence follow ups in adolescence and adulthood in order to show whether the benefits on the motor and functional benefits exist throughout. It is time to conduct a comparative analysis of open fetal surgical interventions and minimally invasive ones with the use of fetoscopy to outline safety and efficiency profiles further. Also, functional and psychosocial assessment strengths should be standardized and a method to identify the biomarkers to reflect which fetuses would respond best to prenatal intervention should be studied. Lastly, caregiver burden assessment and cost-effective analysis will help cast a more magnificent vision of the overall effects of prenatal MMC repair. In conclusion, this meta-analysis supports the idea that prenatal repair significantly improves the results in functional mobility and walking independence, as compared with postnatal repair, without the significant changes in mortality. The impediment of placement of VP shunt is encouraging, albeit not significant. These results favor the application of prenatal surgery in selective cases, including the multidisciplinary approach in a high expertise environment, and point toward the necessity of additional long-term, comparative, and cost-effectiveness research in the future as the basis of clinical decision-making. Conclusion Prenatal surgical correction of myelomeningocele provides significant functional benefits compared to postnatal surgery, resulting in improved walking independence and mobility. Crucially, the death rates for these two methods do not differ much. The placement of VP shunt shows promising results but the results are not statistically significant. These findings support the use of prenatal repair in carefully selected cases, highlighting the need for thorough evaluations of both maternal and fetal risks, expert consultations, and informed patient counseling. Despite these considerable clinical improvements, the lack of a difference in mortality emphasizes the importance of skilled medical teams and careful patient selection. Future investigations should focus on long-term studies that improve quality of life, cost-effectiveness, neurodevelopmental outcomes, and the best time to implement treatments. These insights are essential for guiding clinical decisions and shaping healthcare policy. Declarations Ethical approval: Ethical approval was not required for this study Consent: Informed consent was not required for this study Consent for Publication: Patient/participant/guardian’s consent is not required for the publication of this study Source of funding: None Author contribution: AI: Data Curation, Formal analysis, Writing-Results, Writing- review & editing. HR: Abstract writing, Discussion writing. MD: Data Extraction, Conclusion writing. IK: Protocols writing, Introduction writing, demographic table. LZ: Demographic Tables and Methodology. MUH: Risk of Bias assessment and uncertainty of evidence. MSK: Writing review and Editing. UN: Supervision A.M: Writing, Review and Editing. Conflicts of interest disclosure: The authors declare no conflicts of interest. Acknowledgements: None Data availability : All data generated or analysed during this study are included in this published article and its supplementary information files. Provenance and peer review: Not applicable. Clinical Trial Number: Clinical Trial number not applicable References Janik K, Manire M, Smith GM, Krynska B. Spinal Cord Injury in Myelomeningocele: Prospects for Therapy. Front Cell Neurosci. 2020;14:201. https://doi.org/10.3389/FNCEL.2020.00201 . Raybaud C, Miller E. Radiological Evaluation of Myelomeningocele — Chiari II Malformation. Milano: Springer; 2008. pp. 111–42. https://doi.org/10.1007/978-88-470-0651-5_9 . Boulet SL, Yang Q, Mai C, Kirby RS, Collins JS, Robbins JM, et al. Trends in the postfortification prevalence of spina bifida and anencephaly in the United States. Birth Defects Res Clin Mol Teratol. 2008;82(7):527–32. 10.1002/bdra.20468 . [PubMed: 18481813]. Tamber MS, Flannery AM, McClung-Smith C, Assassi N, Bauer DF, Beier AD, Blount JP, Durham SR, Klimo P Jr, Nikas DC, Rehring P, Tyagi R, Mazzola CA. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Incidence of Shunt-Dependent Hydrocephalus in Infants With Myelomeningocele After Prenatal Versus Postnatal Repair. Neurosurgery. 2019;85(3):E405-E408. 10.1093/neuros/nyz262 . PMID: 31418039. Pollesche J. (2017). Management of Myelomeningocele Study Clinical Trial (2003–2010) . https://hpsrepository.asu.edu/handle/10776/13011 Johnson MP, Bennett KA, Rand L, Burrows PK, Thom EA, Howell LJ, Farrell JA, Dabrowiak ME, Brock JW 3rd, Farmer DL, Adzick NS, Management of Myelomeningocele Study Investigators. The Management of Myelomeningocele Study: obstetrical outcomes and risk factors for obstetrical complications following prenatal surgery. Am J Obstet Gynecol. 2016;215(6):778. .e1-778.e9. Epub 2016 Aug 2. PMID: 27496687; PMCID: PMC5896767. Korenromp MJ, Van Gool JD, Bruinese HW, Kriek R. Early fetal movements in myelomeningocele. Lancet. 1986;1:917–8. [PubMed: 2870386]. Sival DA, Begeer JH, Staal-Schreinemachers AL, et al. Perinatal motor behaviour and neurological outcome in spina bifida aperta. Early Hum Dev. 1997;50:27–37. [PubMed: 9467691]. Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D'Alton ME, Farmer DL. MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. 2011;364(11):993–1004. 10.1056/NEJMoa1014379 . Epub 2011 Feb 9. PMID: 21306277; PMCID: PMC3770179. Johnson MP, Bennett KA, Rand L, Burrows PK, Thom EA, Howell LJ, Farrell JA, Dabrowiak ME, Brock JW 3rd, Farmer DL, Adzick NS. Management of Myelomeningocele Study Investigators. The Management of Myelomeningocele Study: obstetrical outcomes and risk factors for obstetrical complications following prenatal surgery. Am J Obstet Gynecol. 2016. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. 10.1136/bmj.n71 . PMID: 33782057; PMCID: PMC8005924. Farmer DL, Thom EA, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Gupta N, Adzick NS. Management of Myelomeningocele Study Investigators. The Management of Myelomeningocele Study: full cohort 30-month pediatric outcomes. Am J Obstet Gynecol. 2018;218(2):256.e1-256.e13. doi: 10.1016/j.ajog.2017.12.001. Epub 2017 Dec 12. PMID: 29246577; PMCID: PMC7737375. Kalluri AL, Jiang K, Abu-Bonsrah N, Ammar A, Reynolds R, Alomari S, Odonkor MN, Bhimreddy M, Ram N, Robinson S, Akbari SHA, Groves ML. Socioeconomic characteristics and postoperative outcomes of patients undergoing prenatal vs. postnatal repair of myelomeningoceles. Childs Nerv Syst. 2024;40(4):1177–84. 10.1007/s00381-023-06254-y . Epub 2023 Dec 22. PMID: 38133684. Zamłyński J, Olejek A, Koszutski T, Ziomek G, Horzelska E, Gajewska-Kucharek A, Maruniak-Chudek I, Herman-Sucharska I, Kluczewska E, Horak S, Bodzek P, Zamłyński M, Kowalik J, Horzelski T, Bohosiewicz J. Comparison of prenatal and postnatal treatments of spina bifida in Poland–a non-randomized, single-center study. J Matern Fetal Neonatal Med. 2014;27(14):1409-17. 10.3109/14767058.2013.858689 . Epub 2013 Nov 26. PMID: 24156622. Sanz Cortes M, Corroenne R, Pyarali M, Johnson RM, Whitehead WE, Espinoza J, Donepudi R, Castillo J, Castillo H, Mehollin-Ray AR, Shamshirsaz AA, Nassr AA, Belfort MA. Ambulation after in-utero fetoscopic or open neural tube defect repair: predictors for ambulation at 30 months. Ultrasound Obstet Gynecol. 2024;64(2):203–213. 10.1002/uog.27589 . Epub 2024 Jul 3. PMID: 38243917. Risk of bias tools. - Current version of RoB 2. sites.google.com. https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/current-version-of-rob-2?authuser=0 Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [Internet]. www.ohri.ca.2021. Available from: https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp Moldenhauer JS, et al. Fetal myelomeningocele repair: the post-MOMS experience at the Children's Hospital of Philadelphia. Fetal Diagn Ther. 2015;37(3):234–40. https://pubmed.ncbi.nlm.nih.gov/25138132/ . Danzer E, Johnson MP, Adzick NS, Melchiorre PJ. Prenatal repair and physical functioning among children with myelomeningocele: A secondary analysis of a randomized clinical trial. JAMA Pediatr. 2020;174(3):e205674. https://doi.org/10.1001/jamapediatrics.2020.5674 . Additional Declarations No competing interests reported. Supplementary Files Supplementarytablesandfigures.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7216514","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":508687389,"identity":"49183dd7-a803-43b4-b541-543883a55c0c","order_by":0,"name":"Arooba Ishmal","email":"","orcid":"","institution":"MBBS Karachi Medical and Dental College","correspondingAuthor":false,"prefix":"","firstName":"Arooba","middleName":"","lastName":"Ishmal","suffix":""},{"id":508687390,"identity":"c3fc766b-1bf2-4a6a-a7a3-a35c0c9b2e95","order_by":1,"name":"Hamid Rehman","email":"","orcid":"","institution":"Khyber Medical University (KMU)","correspondingAuthor":false,"prefix":"","firstName":"Hamid","middleName":"","lastName":"Rehman","suffix":""},{"id":508687391,"identity":"89f37d99-eca2-495e-a9db-ba3c802c491c","order_by":2,"name":"Manav Das","email":"","orcid":"","institution":"Liaquat University of Medical \u0026 Health Sciences","correspondingAuthor":false,"prefix":"","firstName":"Manav","middleName":"","lastName":"Das","suffix":""},{"id":508687392,"identity":"0fe64b7a-db65-4145-b14c-58258b351b32","order_by":3,"name":"Imad Khan","email":"","orcid":"","institution":"Northwest School of medicine","correspondingAuthor":false,"prefix":"","firstName":"Imad","middleName":"","lastName":"Khan","suffix":""},{"id":508687393,"identity":"80becaf8-3fe5-4e6e-b7ad-4e31717ef386","order_by":4,"name":"Laiba Zaman","email":"","orcid":"","institution":"University College of Medicine \u0026 Dentistry (UCMD)","correspondingAuthor":false,"prefix":"","firstName":"Laiba","middleName":"","lastName":"Zaman","suffix":""},{"id":508687394,"identity":"c610782d-09c9-4bda-8df5-72ef6403f89d","order_by":5,"name":"Minhaj Ul Hassan","email":"","orcid":"","institution":"Liaquat University of Medical \u0026 Health Sciences","correspondingAuthor":false,"prefix":"","firstName":"Minhaj","middleName":"Ul","lastName":"Hassan","suffix":""},{"id":508687395,"identity":"ba5c3217-e17e-4b54-a124-4cbfd65922f0","order_by":6,"name":"Muhammad Saad Khan","email":"","orcid":"","institution":"Jinnah Sindh Medical University","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"Saad","lastName":"Khan","suffix":""},{"id":508687396,"identity":"b979a378-ec8e-4784-8951-a9f58e063af3","order_by":7,"name":"Umaima Naeem","email":"","orcid":"","institution":"MBBS Graduate Jinnah Sindh Medical University","correspondingAuthor":false,"prefix":"","firstName":"Umaima","middleName":"","lastName":"Naeem","suffix":""},{"id":508687397,"identity":"d57e7e66-98b3-4cbe-98bf-618c841462f0","order_by":8,"name":"Abubakr Mahmoud","email":"data:image/png;base64,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","orcid":"","institution":"University of Khartoum","correspondingAuthor":true,"prefix":"","firstName":"Abubakr","middleName":"","lastName":"Mahmoud","suffix":""}],"badges":[],"createdAt":"2025-07-25 17:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7216514/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7216514/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90464381,"identity":"f9549e06-5755-48f6-891b-c23fb45414fe","added_by":"auto","created_at":"2025-09-03 05:09:03","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":88724,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePRISMA FLOWCHART\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7216514/v1/235b24152d6b5f27b78256f9.jpeg"},{"id":90464391,"identity":"c36dd7a9-e475-4f86-bdba-93c3127c5fdd","added_by":"auto","created_at":"2025-09-03 05:09:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":7703,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCOMPARISON OF FUNCTIONAL MOBILITY IN PRENATAL VS POSTNATAL SURGERY\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7216514/v1/7a83221b72d049a9f68dca93.png"},{"id":90464396,"identity":"4ac32cde-df2b-4520-b352-18c63587fce0","added_by":"auto","created_at":"2025-09-03 05:09:07","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":7574,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCOMPARISON OF WALKING INDEPENDENCE IN PRENATAL VS POSTNATAL SURGERY\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7216514/v1/9d234e12ef2c7a91c3ff6033.png"},{"id":90464409,"identity":"75d7eed1-f63a-4334-a41e-6982dd3750f3","added_by":"auto","created_at":"2025-09-03 05:09:10","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":241186,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCOMPARISON OF MORTALITY IN PRENATAL VS POSTNATAL SURGERY\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7216514/v1/a4a00d99657aa3dd5e51bf57.jpeg"},{"id":90464388,"identity":"eb352ab2-70c7-4f39-8e22-ec22eba55e8e","added_by":"auto","created_at":"2025-09-03 05:09:04","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":7891,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7216514/v1/0a4cb7b9c22bfebb1f70a7de.png"},{"id":90799980,"identity":"db6572af-c19a-4757-8c3e-d97d9158a6ad","added_by":"auto","created_at":"2025-09-08 10:02:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1632924,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7216514/v1/5b94fd2a-2089-423c-bd8b-d08049c0e566.pdf"},{"id":90464398,"identity":"bfb2f287-96fd-47fb-a63d-28d35e78e29d","added_by":"auto","created_at":"2025-09-03 05:09:08","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":72387,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytablesandfigures.docx","url":"https://assets-eu.researchsquare.com/files/rs-7216514/v1/1030bffb3cff1d3aef30ce83.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"A comparison of prenatal and postnatal repair of myelomeningocele: a systematic review and meta- analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMyelomeningocele (MMC) is the most common congenital defect of the central nervous system, resulting from incomplete neural tube closure early in gestation, typically within the first 6 weeks, leading to significant lifelong disabilities.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e The approximate incidence of myelomeningocele (MM) in the United States is 3.4 per 10, 000 live births.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e Live-born infants with MM have an approximately 10% risk of mortality, and survivors face significant morbidity. Conventional treatment of MM has been to perform a postnatal repair within 48 hours after birth. After repair of the defect, neurosurgeons must remain vigilant about recognizing and treating hydrocephalus, which is a frequent comorbidity in MM patients.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e The NIH-sponsored Management of Myelomeningocele Study (MOMS) was initiated in 2003 to compare the safety and efficacy of prenatal repair of myelomeningocele with that of standard postnatal repair. The trial was stopped in 2010 before reaching the target sample size, at the recommendation of its Data and Safety Monitoring Committee (DSMC), in accordance with the stopping rules for the efficacy of prenatal surgery.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e Results of the trial were reported based on 158 women who had undergone randomization before July 1, 2009, as this was the cohort analyzed for the DSMC. Findings in that report demonstrated a significant improvement in the primary outcomes at 12 and 30 months of age, and in multiple secondary outcomes, including reversal of hindbrain herniation and ambulation by 30 months, in the prenatal repair group.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eSequential ultrasonographic images that are obtained from fetuses with myelomeningocele suggest that insults to both the central and peripheral nervous systems may be progressive. Movement in the lower limbs may be lost, and hindbrain herniation and hydrocephalus may worsen during fetal gestation.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e Historically, myelomeningocele has been managed with surgical repair after birth. However, prenatal (in utero) repair has emerged as an alternative that may prevent progression of neurologic damage caused by prolonged exposure of neural tissue to amniotic fluid and mechanical trauma. However, it also carries risks such as preterm birth and maternal morbidity.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eTaking all the above into account, the main aim of this systematic review and meta-analysis was to compare Motor function in patients following treatment of myelomeningocele through postnatal vs prenatal surgical repair, as assessed by Walking status (independent vs assisted), Peabody Developmental Motor Scales (PDMS-2) gross motor score or any other validated criteria. This review will gather global evidence to answer: Which approach truly gives babies and families the best shot at a healthier future? Existing reviews lack synthesis of recent evidence, long-term neurological outcomes, and maternal morbidity, creating clinical uncertainty. This meta-analysis addresses gaps by comparing prenatal vs. postnatal repair across diverse outcomes (mobility, ambulation, shunt rates, mortality), providing updated insights for risk-benefit counseling.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003e\u003cstrong\u003eData sources and search strategy\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThis meta-analysis was conducted conclusively with the Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. \u003csup\u003e\u003cstrong\u003e\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/strong\u003e\u003c/sup\u003e A comprehensive electronic search of PubMed (Medline), Sci-Hub Scopus, and Cochrane Central databases was conducted from inception to MAY 2025.. The following search terms were used: (Meningomyelocele OR \"\"Meningomyelocele\"\"[Mesh])) AND (Postnatal) AND (Prenatal) AND (Mortality OR post-operative complications OR treatment outcomes OR \"\"Postoperative Complications\"\"[Mesh] OR \"\"Mortality\"\"[Mesh] OR \"\"Treatment Outcome\"\"[Mesh])\" Two unbiased authors (LZ and MD) searched without limitations or conflicts of interest. A search was conducted for relevant published or unpublished clinical trials. Furthermore, we conducted a search of the reference lists of the included research, as well as related meta-analyses and review articles, to identify possibly relevant studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Selection\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe eligibility criteria were Randomized controlled trials (RCTs) and Cohorts, with a target population of fetus or neonates diagnosed with Myelomeningocele (MMC). All studies had participants with singleton pregnancies where the MMC lesions were located between thoracic level t1 and sacral level s1 with evidence of hind brain herniation, involving postnatal repair compared with prenatal repair for myelomeningocele. We excluded review articles, protocols, uncontrolled trials, and observational studies other than cohort studies (e.g., case-control and cross-sectional designs).\u003c/p\u003e\n\u003cp\u003eAdditionally, commentaries, letters to the editor, and case reports were excluded. \u0026ldquo;The study selection process is depicted in the PRISMA 2020 flow diagram\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Extraction and Assessment of Study Quality\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eDuplicate studies were removed from the list after exporting the retrieved articles to Endnote Reference Library Software. All data extracted from the included studies during this systematic review and meta-analysis are available from the corresponding author upon reasonable request. Two reviewers (LZ AND MD) then carefully assessed the remaining articles, and only those that met the previously stated eligibility conditions were included. All the articles were first screened based on the abstract and title. After that, the remaining articles were screened through the full text.\u003c/p\u003e\n\u003cp\u003eA third reviewer (AI) was consulted to resolve any disagreements regarding the results. An online Microsoft Excel spreadsheet was created using data from the completed studies for the baseline characteristics and outcomes. Baseline parameters are as follows: Maternal age, Maternal BMI, presence of chiari II malformation, Prevalence of Hydrocephalus, Hind brain herniation severity.\u003c/p\u003e\n\u003cp\u003eThese outcomes were included:\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary Outcomes\u003c/strong\u003e:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eMotor function at 30 months\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eAmbulation status\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eSECONDARY OUTCOMES\u003c/strong\u003e:\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003eVentriculoperitoneal shunt (VP) shunt placement\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003eNeonatal Mortality\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe modified Cochrane Collaboration risk of bias technique was utilized to check the reliability of the included studies. Quality assessment and risk of bias were independently assessed using the \u003cstrong\u003eCochrane Risk of Bias Tool 2\u003c/strong\u003e for the randomized controlled trial, and the \u003cstrong\u003eNewcastle\u0026ndash;Ottawa Scale (NOS)\u003c/strong\u003e for the cohort studies, by two investigators. The results were matched, and any discrepancies were resolved by team consensus.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMeta-analysis\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThis meta-analysis used Review Manager (version 5.4. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Forest plots were generated for the results' visual display. The outcomes were displayed as risk ratios (RR) with a 95% confidence interval using the random effects model. Statistical heterogeneity was assessed using the I\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Statistics, with values greater than 50% considered indicative of substantial heterogeneity among the 4 included studies.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eStudy selection\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe searches yielded 42 articles from PubMed and Cochrane Central databases. After filtering duplicates and excluding irrelevant articles based on title, 11 articles were examined for the availability of full texts and data related to the research objective. Following the assessment of complete texts, 4 articles were included for analysis. \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003eThe study selection steps are presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eCharacteristics of studies\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eAll four of the included articles compared outcomes of patients undergoing pre-natal vs post-natal surgical repair for myelomeningocele. Detailed characteristics of the included studies and the results of each study are outlined in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e (Baseline Characteristics). The study by Diane L. Farmer et al. was a randomized control trial (2020) was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Clinical and Translational Science Awards, National Institutes of Health.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e The study by Jacek Zamłyn\u0026acute; ski et al. was a non-randomized, single center study conducted in Poland where screening for MMC occurred between 2005 and 2011 by tertiary perinatal centers and laboratories of prenatal diagnosis with FMF certification.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e M. Sanz Cortez et al. conducted a retrospective review of a cohort of children who underwent open neural defect repair between November 2011 and May 2023.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e The 2023 study by Anita L. Kalluri presented a retrospective review of all patients who underwent MMC repair between 2012 and 2022 at a single pediatric neurological tertiary care center.\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Characteristics\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnita L. Kalluri\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eJacek Zamłynski\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eM. Sanz Cortes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDiana L. Farmer\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePopulation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003efetuses or neonates diagnosed with myelomeningocele (MMC)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003efetuses or neonates diagnosed with myelomeningocele (MMC)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003efetuses or neonates diagnosed with myelomeningocele (MMC)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003efetuses or neonates diagnosed with myelomeningocele (MMC)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePrenatal repair for myelomeningocele\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePrenatal repair for myelomeningocele\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePrenatal repair for myelomeningocele\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePrenatal repair for myelomeningocele\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eControl\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePostnatal repair for myelomeningocele\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePostnatal repair for myelomeningocele\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePostnatal repair for myelomeningocele\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePostnatal repair for myelomeningocele\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStudy design\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCohort\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCohort\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCohort\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRCT\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal number of patients\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79 patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e93 patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e161 patients\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e183 patients\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMaternal Age (years)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28 (19\u0026ndash;45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e29.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMaternal Age (years) control\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27 (17\u0026ndash;24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e28.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMaternal BMI (kg/m\u0026sup2;)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25.8 (18.5\u0026ndash;37.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMaternal BMI (kg/m\u0026sup2;)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eControl\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30.4 (17.9\u0026ndash;60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHindbrain Herniation: I \u0026ndash; Small intervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(6.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHindbrain Herniation: I \u0026ndash; Small control\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (4.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHindbrain Herniation: II \u0026ndash; Mild intervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43 (93.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHindbrain Herniation: severe intervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e27(29.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHindbrain Herniation: severe control\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23 (25.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLesion Level Intervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (96.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLesion Level control\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (89.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e97.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLesion Level_2\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e84(76.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLesion Level_2\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eControl\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (10.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e40(78.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eThoracic Level Involved Intervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eThoracic Level Involved Control\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (10.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLumbar Level Involved\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30 (100.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35(87.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLumbar Level Involved control\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46 (100.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31(79.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSacral Level Involved\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (96.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5(12.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e83.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSacral Level Involved\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eControl\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (89.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7(17.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e72.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChiari 2 Malformation\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (96.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e93.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChiari 2 Malformation control\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (87.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHydrocephalus\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15(50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37(33.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHydrocephalus\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eControl\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28(59.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e40(78.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFoot Deformity\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntervention\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10(33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(4.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23(20.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e24(26.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFoot Deformity\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eControl\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20(40.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(6.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17(33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e19(20.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCorpus Callosum Agenesis, n (%)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntervention group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8(17.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"1\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e8 (17.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e\u003ccolgroup cols=\"1\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes: 90 (99%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCorpus Callosum Agenesis, n (%)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eControl group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9(19.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (19.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNO: 1 (1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFemale fetal sex\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eIntervention group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (63%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23(50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e(0.61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e42(46.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFemale fetal sex\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eControl group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (57.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29(61.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27(52.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e57(62.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIntact Motor At Birth (WALKING DEPENDENTLY)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e32(60.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIntact Motor\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eAt Birth (WALKING INDEPENDENTLY)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2(11.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50(87.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eRisk of bias assessment\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe quality of individual studies analysis was conducted according to the study design using Cochrane Risk of Bias Tool 2,\u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e for the randomized controlled trial, where this checklist was used to analyze the risk of bias in the studies. The results of the risk of bias assessment are presented in supplementary Fig.\u0026nbsp;1. The Newcastle\u0026ndash;Ottawa Scale (NOS) \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e was used for quality assessment of the cohort studies, the results are presented in supplementary table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePRIMARY OUTCOMES\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the forest plot comparing functional mobility in prenatal vs postnatal group. The functional mobility in the study by Anita L. Kalluri and M. Sanz Cortez was assessed at 12 months of age, while the Diane L. farmer study was assessed at 30 months through the Bayley Scales of Infant and Toddler Development (BSID) II psychomotor development index, and the score of \u0026ge;\u0026thinsp;85 was taken as a marker for normal motor function. The pooled analysis shows a risk ratio (RR) of 2.45 (95% CI: 1.72\u0026ndash;3.47) which shows that prenatal repair of myelomeningocele is associated with better motor function compared to post-natal repair. The p value (P\u0026thinsp;\u0026lt;\u0026thinsp;0.00001) suggests the difference is statistically significant and the heterogeneity I\u0026sup2; = 0% indicates consistency of results across the studies.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e compares the outcomes of independent ambulation in prenatal vs postnatal repair group. The pooled analysis shows a risk ratio of 2.33 (95% CI: 1.52\u0026ndash;3.55) which indicates that infants who have undergone prenatal repair of myelomeningocele are 2.33 times more likely to walk independently than those who have undergone postnatal repair. The p value of less than 0.0001 indicates that the results are statistically significant and the relatively low heterogeneity demonstrates consistency of results across studies.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSECONDARY OUTCOMES\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e represents a forest plot comparing the placement of ventriculoperitoneal (VP) shunt in patients after prenatal surgery for repair of myelomeningocele vs postnatal surgery. The risk ratio of 0.52 (95% CI: 0.26\u0026ndash;1.02) indicates the risk of VP shunt placement was lower in prenatal group. The p value is 0.06 which suggesting a strong trend toward benefit with prenatal intervention that does not reach the threshold for significance. The heterogeneity is relatively high (I\u0026sup2; = 69%) indicating significant variations across the studies.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe forest plot in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e compares the outcomes of mortality between the prenatal and the postnatal repair of myelomeningocele. The pooled analysis shows a risk ratio of 1.49 (95% CI: 0.49\u0026ndash;4.51) indicating that the prenatal group is associated with higher rates of mortality than the postnatal group, however the p value (P\u0026thinsp;=\u0026thinsp;0.48) suggests that the results are not statistically significant, hence the result is inconclusive. The very low heterogeneity I\u0026sup2; = 3% indicates consistency of results across the studies.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePublication Bias\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eSince there are fewer studies (4), we could not make funnel plots and perform Egger's regression test for accessing publication bias.\u003c/p\u003e\u003cp\u003e\u003cb\u003eUncertainty of Evidence\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe summary of findings table shows the evidence on the effect of prenatal surgical repair for myelomeningocele compared to postnatal repair. According to moderate certainty evidence prenatal repair likely improves walking independence and functional mobility. However, it may also increase mortality according to low certainty evidence. Furthermore, the need for VP shunt placement is uncertain due to very low certainty evidence (Supplementary Table\u0026nbsp;2).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e This meta-analysis is a modern and thorough review that compares the effectiveness of prenatal and postnatal surgical repair of myelomeningocele (MCC) regarding important outcomes such as mobility, independent walking, ventriculoperitoneal (VP) shunt placement, and death. The incorporation of recent RCTs and prospective studies into this analysis provides a more detailed view of the functional and neurological advantages, as well as the limitations and risks, of prenatal surgery.\u003c/p\u003e\u003cp\u003eThere was a statistically significant improvement of functional mobility in prenatal repair favor. In three randomized controlled trials (380 participants; 208 prenatal and 172 postnatal), prenatal repair turned the probability of having an improvement of functional mobility, with an overall risk ratio (RR) of 2.45 (95% CI: 1.72\u0026ndash;3.47; p\u0026thinsp;\u0026lt;\u0026thinsp;0.00001), and no heterogeneity (I\u0026sup2; = 0). These data support the previous ones that were provided by the landmark MOMS trial and its follow-ups which confirmed better motor performances at 30 months of age in the prenatal group than in the postnatal group. \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e Danzer et al. (2020) showed better lower limbs functioning among patients having prenatal repair, and Sanz-Cortes et al. (2024) mentioned the success of fetoscopic procedures in relation to motor functioning. \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eRegarding walking independence, 3 studies and 374 participants (215 prenatal, 159 postnatal) showed that prenatal surgery had a significant impact on ambulation outcomes (RR\u0026thinsp;=\u0026thinsp;2.33, 95% CI: 1.52\u0026ndash;3.55; p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001, I\u0026sup2; = 13%). The result concurs with other previous findings by MOMS trial who recorded increased ambulation in the prenatal group. \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e The uniformity of research studies indicates that the prenatal repair may provide factual functional benefit, possibly by spinal cord protection.\u003c/p\u003e\u003cp\u003eIn terms of VP shunt placement, the data of 291 persons (134 prenatal, 157 postnatal) indicates that prenatal surgery can reduce the threat due to a 48 percent probability (RR\u0026thinsp;=\u0026thinsp;0.52, 95% CI: 0.26\u0026ndash;1.02; p\u0026thinsp;=\u0026thinsp;0.06), but it failed to be statistically significant. The level of heterogeneity was moderate (I\u0026sup2; = 69%), which may indicate indifferences in used criteria of shunts and institutional guidelines. However, this correlates with previous reports that were expressed with reduced frequency of hydrocephalus and hindbrain herniation in the prenatal cohort. \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e In a similar fashion, Moldenhauer et al. (2015) and Kernaghan D, Mauer E, Farmer DL, et al. reported lower levels of shunt dependency in patients of the prenatal cohort. \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eLastly in case of mortality, results of four studies indicated that there is no statistically significant modification between the prenatal and postnatal repair groups (RR\u0026thinsp;=\u0026thinsp;1.44, 95% CI: 0.50\u0026ndash;4.13; p\u0026thinsp;=\u0026thinsp;0.49), with low heterogeneity (I\u0026sup2; = 1%). One would think that the point estimate reflects the higher mortality rates in the prenatal community, but it is not statistically so. The safety of prenatal surgery, which has been reported previously and by the MOMS trial as well as Zamelinski et al. (2014), has been confirmed by previous reports. \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e Nonetheless, the risk of experience to mothers, e.g., uterine rupture, chorioamniotic separation, preterm premature rupture of membranes, etc. is still not trivial, particularly when it is open fetal surgery \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e. Those of these maternal risks can be alleviated with some of the emerging techniques such as fetoscopic repair. \u003csup\u003e\u003cb\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNotwithstanding such positive results, the presented meta-analysis has its limitations. The available studies are also insufficient and do not allow subgroup and sensitivity analyses to be robust. Heterogeneity in the methods used during surgery, postoperative treatment and standards of determining the outcomes evaluation also exists, especially in VP shunt placement results. Moreover, the follow-up times of the majority of the studies are inadequate to fully report neurodevelopmental, educational, and psychosocial results in adults. In what is frequently put in force during functional assessments, parental reporting creates bias subjectivity.\u003c/p\u003e\u003cp\u003eThere are a few strengths of this meta-analysis. First, it comprises a restricted set of randomized control trials (RCTs) and prospective studies that have the utmost support in terms of clinical evidence. Recent studies have been included to provide the synthesis of the recent studies of prenatal versus postnatal repair outcomes in myelomeningocele (MMC). Functional mobility, the need for VP shunt, independent ambulation and mortality were reported with clear outcome measures across information and these improvements made comparability and internal validity. Second, the study used thorough methodology in the analysis and used PRISMA method of analysis, clear selection criteria, and a strong statistical synthesis with tests of heterogeneity. Regarding the major results such as walking independence and functional mobility, the heterogeneity was zero (I\u0026sup2;: 0%), which means that the studies included comparable results, and the findings added in the background led to a higher probability of accurate results.\u003c/p\u003e\u003cp\u003eFuture studies must focus on the long term senescence follow ups in adolescence and adulthood in order to show whether the benefits on the motor and functional benefits exist throughout. It is time to conduct a comparative analysis of open fetal surgical interventions and minimally invasive ones with the use of fetoscopy to outline safety and efficiency profiles further. Also, functional and psychosocial assessment strengths should be standardized and a method to identify the biomarkers to reflect which fetuses would respond best to prenatal intervention should be studied. Lastly, caregiver burden assessment and cost-effective analysis will help cast a more magnificent vision of the overall effects of prenatal MMC repair.\u003c/p\u003e\u003cp\u003eIn conclusion, this meta-analysis supports the idea that prenatal repair significantly improves the results in functional mobility and walking independence, as compared with postnatal repair, without the significant changes in mortality. The impediment of placement of VP shunt is encouraging, albeit not significant. These results favor the application of prenatal surgery in selective cases, including the multidisciplinary approach in a high expertise environment, and point toward the necessity of additional long-term, comparative, and cost-effectiveness research in the future as the basis of clinical decision-making.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePrenatal surgical correction of myelomeningocele provides significant functional benefits compared to postnatal surgery, resulting in improved walking independence and mobility. Crucially, the death rates for these two methods do not differ much. The placement of VP shunt shows promising results but the results are not statistically significant. These findings support the use of prenatal repair in carefully selected cases, highlighting the need for thorough evaluations of both maternal and fetal risks, expert consultations, and informed patient counseling. Despite these considerable clinical improvements, the lack of a difference in mortality emphasizes the importance of skilled medical teams and careful patient selection.\u003c/p\u003e\u003cp\u003eFuture investigations should focus on long-term studies that improve quality of life, cost-effectiveness, neurodevelopmental outcomes, and the best time to implement treatments. These insights are essential for guiding clinical decisions and shaping healthcare policy.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval was not required for this study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was not required for this study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatient/participant/guardian’s consent is not required for the publication of this study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSource of funding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAI: Data Curation, Formal analysis, Writing-Results, Writing- review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003eHR: Abstract writing, Discussion writing.\u003c/p\u003e\n\u003cp\u003eMD: Data Extraction, Conclusion writing.\u003c/p\u003e\n\u003cp\u003eIK: Protocols writing, Introduction writing, demographic table.\u003c/p\u003e\n\u003cp\u003eLZ: Demographic Tables and Methodology.\u003c/p\u003e\n\u003cp\u003eMUH: Risk of Bias assessment and uncertainty of evidence.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;MSK: Writing review and Editing.\u003c/p\u003e\n\u003cp\u003eUN: Supervision\u003c/p\u003e\n\u003cp\u003eA.M: Writing, Review and Editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest disclosure:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analysed during this study are included in this published article and its supplementary information files.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eProvenance and peer review:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical Trial number not applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eJanik K, Manire M, Smith GM, Krynska B. Spinal Cord Injury in Myelomeningocele: Prospects for Therapy. Front Cell Neurosci. 2020;14:201. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/FNCEL.2020.00201\u003c/span\u003e\u003cspan address=\"10.3389/FNCEL.2020.00201\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRaybaud C, Miller E. Radiological Evaluation of Myelomeningocele \u0026mdash; Chiari II Malformation. Milano: Springer; 2008. pp. 111\u0026ndash;42. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/978-88-470-0651-5_9\u003c/span\u003e\u003cspan address=\"10.1007/978-88-470-0651-5_9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBoulet SL, Yang Q, Mai C, Kirby RS, Collins JS, Robbins JM, et al. Trends in the postfortification prevalence of spina bifida and anencephaly in the United States. Birth Defects Res Clin Mol Teratol. 2008;82(7):527\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/bdra.20468\u003c/span\u003e\u003cspan address=\"10.1002/bdra.20468\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. [PubMed: 18481813].\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTamber MS, Flannery AM, McClung-Smith C, Assassi N, Bauer DF, Beier AD, Blount JP, Durham SR, Klimo P Jr, Nikas DC, Rehring P, Tyagi R, Mazzola CA. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on the Incidence of Shunt-Dependent Hydrocephalus in Infants With Myelomeningocele After Prenatal Versus Postnatal Repair. Neurosurgery. 2019;85(3):E405-E408. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/neuros/nyz262\u003c/span\u003e\u003cspan address=\"10.1093/neuros/nyz262\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 31418039.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePollesche J. (2017). \u003cem\u003eManagement of Myelomeningocele Study Clinical Trial (2003\u0026ndash;2010)\u003c/em\u003e. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://hpsrepository.asu.edu/handle/10776/13011\u003c/span\u003e\u003cspan address=\"https://hpsrepository.asu.edu/handle/10776/13011\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJohnson MP, Bennett KA, Rand L, Burrows PK, Thom EA, Howell LJ, Farrell JA, Dabrowiak ME, Brock JW 3rd, Farmer DL, Adzick NS, Management of Myelomeningocele Study Investigators. The Management of Myelomeningocele Study: obstetrical outcomes and risk factors for obstetrical complications following prenatal surgery. Am J Obstet Gynecol. 2016;215(6):778. .e1-778.e9. Epub 2016 Aug 2. PMID: 27496687; PMCID: PMC5896767.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKorenromp MJ, Van Gool JD, Bruinese HW, Kriek R. Early fetal movements in myelomeningocele. Lancet. 1986;1:917\u0026ndash;8. [PubMed: 2870386].\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSival DA, Begeer JH, Staal-Schreinemachers AL, et al. Perinatal motor behaviour and neurological outcome in spina bifida aperta. Early Hum Dev. 1997;50:27\u0026ndash;37. [PubMed: 9467691].\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAdzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D'Alton ME, Farmer DL. MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. 2011;364(11):993\u0026ndash;1004. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1014379\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa1014379\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2011 Feb 9. PMID: 21306277; PMCID: PMC3770179.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJohnson MP, Bennett KA, Rand L, Burrows PK, Thom EA, Howell LJ, Farrell JA, Dabrowiak ME, Brock JW 3rd, Farmer DL, Adzick NS. Management of Myelomeningocele Study Investigators. The Management of Myelomeningocele Study: obstetrical outcomes and risk factors for obstetrical complications following prenatal surgery. Am J Obstet Gynecol. 2016.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePage MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hr\u0026oacute;bjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/bmj.n71\u003c/span\u003e\u003cspan address=\"10.1136/bmj.n71\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 33782057; PMCID: PMC8005924.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFarmer DL, Thom EA, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Gupta N, Adzick NS. Management of Myelomeningocele Study Investigators. The Management of Myelomeningocele Study: full cohort 30-month pediatric outcomes. Am J Obstet Gynecol. 2018;218(2):256.e1-256.e13. doi: 10.1016/j.ajog.2017.12.001. Epub 2017 Dec 12. PMID: 29246577; PMCID: PMC7737375.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKalluri AL, Jiang K, Abu-Bonsrah N, Ammar A, Reynolds R, Alomari S, Odonkor MN, Bhimreddy M, Ram N, Robinson S, Akbari SHA, Groves ML. Socioeconomic characteristics and postoperative outcomes of patients undergoing prenatal vs. postnatal repair of myelomeningoceles. Childs Nerv Syst. 2024;40(4):1177\u0026ndash;84. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00381-023-06254-y\u003c/span\u003e\u003cspan address=\"10.1007/s00381-023-06254-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2023 Dec 22. PMID: 38133684.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZamłyński J, Olejek A, Koszutski T, Ziomek G, Horzelska E, Gajewska-Kucharek A, Maruniak-Chudek I, Herman-Sucharska I, Kluczewska E, Horak S, Bodzek P, Zamłyński M, Kowalik J, Horzelski T, Bohosiewicz J. Comparison of prenatal and postnatal treatments of spina bifida in Poland\u0026ndash;a non-randomized, single-center study. J Matern Fetal Neonatal Med. 2014;27(14):1409-17. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3109/14767058.2013.858689\u003c/span\u003e\u003cspan address=\"10.3109/14767058.2013.858689\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2013 Nov 26. PMID: 24156622.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSanz Cortes M, Corroenne R, Pyarali M, Johnson RM, Whitehead WE, Espinoza J, Donepudi R, Castillo J, Castillo H, Mehollin-Ray AR, Shamshirsaz AA, Nassr AA, Belfort MA. Ambulation after in-utero fetoscopic or open neural tube defect repair: predictors for ambulation at 30 months. Ultrasound Obstet Gynecol. 2024;64(2):203\u0026ndash;213. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/uog.27589\u003c/span\u003e\u003cspan address=\"10.1002/uog.27589\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Epub 2024 Jul 3. PMID: 38243917.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRisk of bias tools. - Current version of RoB 2. sites.google.com. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/current-version-of-rob-2?authuser=0\u003c/span\u003e\u003cspan address=\"https://sites.google.com/site/riskofbiastool/welcome/rob-2-0-tool/current-version-of-rob-2?authuser=0\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWells G, Shea B, O\u0026rsquo;Connell D, Peterson J, Welch V, Losos M et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [Internet]. www.ohri.ca.2021. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ohri.ca/programs/clinical_epidemiology/oxford.asp\u003c/span\u003e\u003cspan address=\"https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMoldenhauer JS, et al. Fetal myelomeningocele repair: the post-MOMS experience at the Children's Hospital of Philadelphia. Fetal Diagn Ther. 2015;37(3):234\u0026ndash;40. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://pubmed.ncbi.nlm.nih.gov/25138132/\u003c/span\u003e\u003cspan address=\"https://pubmed.ncbi.nlm.nih.gov/25138132/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDanzer E, Johnson MP, Adzick NS, Melchiorre PJ. Prenatal repair and physical functioning among children with myelomeningocele: A secondary analysis of a randomized clinical trial. JAMA Pediatr. 2020;174(3):e205674. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jamapediatrics.2020.5674\u003c/span\u003e\u003cspan address=\"10.1001/jamapediatrics.2020.5674\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Myelomeningocele, Prenatal Surgery, Postnatal Repair, Motor Function, Systematic Review","lastPublishedDoi":"10.21203/rs.3.rs-7216514/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7216514/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003cbr\u003e\nMyelomeningocele (MMC), the most severe form of spina bifida, is associated with lifelong disability due to incomplete neural tube closure. Traditionally repaired postnatally, prenatal surgical intervention has emerged as a promising alternative, potentially preventing neurological deterioration. This meta-analysis aimed to compare prenatal and postnatal surgical repair of MMC in terms of motor function, ambulation, shunt dependency, and mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003cbr\u003e\nA comprehensive search of PubMed, Scopus, and Cochrane databases was conducted through May 2025. Eligible studies included randomized controlled trials and cohort studies comparing prenatal and postnatal MMC repair. Primary outcomes were motor function and walking independence. Secondary outcomes included ventriculoperitoneal (VP) shunt placement and neonatal mortality. Risk of bias was assessed using the Cochrane RoB2 and Newcastle–Ottawa Scale.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003cbr\u003e\nFour studies (N=516 patients) met inclusion criteria. Prenatal repair significantly improved functional mobility (RR = 2.45, 95% CI: 1.72–3.47, p \u0026lt; 0.00001, I² = 0%) and walking independence (RR = 2.33, 95% CI: 1.52–3.55, p \u0026lt; 0.0001, I² = 13%). A trend toward reduced VP shunt placement was observed in the prenatal group (RR = 0.52, p = 0.06), though not statistically significant. Mortality was slightly higher in the prenatal group (RR = 1.49, p = 0.48), but without significance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003cbr\u003e\nPrenatal MMC repair yields superior motor outcomes and greater walking independence without significantly affecting mortality. While shunt dependency may be reduced, further research is required to confirm long-term safety and optimize patient selection. Prenatal surgery should be considered in specialized centers with multidisciplinary expertise.\u003c/p\u003e","manuscriptTitle":"A comparison of prenatal and postnatal repair of myelomeningocele: a systematic review and meta- analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-03 05:08:45","doi":"10.21203/rs.3.rs-7216514/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"310b8c39-c5d7-4246-8100-db208159c3e8","owner":[],"postedDate":"September 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-08T09:54:02+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-03 05:08:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7216514","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7216514","identity":"rs-7216514","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}