| Domain | Key finding | Evidence type/sample | Quantitative result | Source/date/URL |
|---|---|---|---|---|
| Genetics / structural variation | Common 22q11.2 deletion is a strong risk factor for meningomyelocele; CRKL prioritized as key deleted gene, with folate-sensitive effect in mouse follow-up | Human trio exome/genome sequencing; 715 parent-offspring trios in Spina Bifida Sequencing Consortium, plus independent 22q11.2 deletion cohort of 1,522 individuals (pqac-00000011, pqac-00000012) | 6/715 cases had 22q11.2del (0.839%); OR vs gnomAD 22.98 (95% CI 6.47–81.61; P=9.16×10^-6); independent 22q11.2del cohort: 8/1522 with MM (0.526%), OR 12.28–15.54 depending on comparator (pqac-00000011, pqac-00000012) | Vong et al., *Science* 2024-05-03, DOI: 10.1126/science.adl1624, https://doi.org/10.1126/science.adl1624 (pqac-00000011, pqac-00000012) |
| Genetics / GWAS | Novel exonic loci identified in Bangladeshi spina bifida case-control/trio study | Human genotyping study; 112 case children, 121 control children, 272 mothers, 128 trios (pqac-00000015) | Trio TDT hits: rs140199800 (*SULT1C2*) P=1.9×10^-7; rs45580033 (*ASB2*) P=4.2×10^-10; rs75426652 (*LHPP*) P=7.2×10^-14; no genome-wide significant variants in case-control models (pqac-00000015) | Tindula et al., *Birth Defects Research* 2024-03, DOI: 10.1002/bdr2.2331, https://doi.org/10.1002/bdr2.2331 (pqac-00000015) |
| Genetics / systems biology WGS | Rare likely gene-disrupting variants implicate pathway-level risk rather than single-gene hits; enriched pathways include carbon metabolism, inflammation, innate immunity, cytoskeletal regulation, transcription | Human ancestry-matched whole-genome case-control analysis; 149 cases + 149 controls after QC/matching (pqac-00000013) | 41,005,720 cohort-level variants initially; 22,502,019 rare variants retained; RF model AUROC 0.78; 439 discriminatory genes highlighted for enrichment analysis (pqac-00000013) | Aguiar-Pulido et al., *PNAS* 2021-12-16, DOI: 10.1073/pnas.2106844118, https://doi.org/10.1073/pnas.2106844118 (pqac-00000013) |
| Surgery / long-term outcomes | Prenatal repair improves mobility and reduces hydrocephalus-related surgery burden at school age, but not overall adaptive behavior | Human follow-up cohort from randomized MOMS trial; 161 children assessed at age 5.9–10.3 years (pqac-00000014) | Vineland composite 89.0 vs 87.5 (P=.35); walking without orthotics/devices 29% vs 11% (P=.06); FRESNO 92±9 vs 85±18 (P<.001); hindbrain herniation 60% vs 87% (P<.001); shunt placement 49% vs 85% (P<.001); shunt revisions 47% vs 70% (P=.02) (pqac-00000014) | Houtrow et al., *Pediatrics* 2020-02, DOI: 10.1542/peds.2019-1544, https://doi.org/10.1542/peds.2019-1544 (pqac-00000014) |
| Epidemiology / mortality | Long-term Swedish registry shows falling prevalence and major first-year survival gains; adult deaths emphasize psychosocial and urinary/bladder risks | Population-based registry study in Sweden; 1,735 people with spina bifida, 1973–2021 (pqac-00000016) | Prevalence fell from 5.2 to 1.2 per 10,000 births; first-year survival rose from 75% to 94%; childhood causes of death: congenital abnormalities, hydrocephalus, infections; adult excesses included self-inflicted injuries/substance abuse and bladder malignancy (pqac-00000016) | Andersson et al., *Acta Paediatrica* 2024-05, DOI: 10.1111/apa.17275, https://doi.org/10.1111/apa.17275 (pqac-00000016) |
| Epidemiology / mortality synthesis | Infant and neonatal mortality have declined over time; prematurity and low birthweight are the strongest infant mortality predictors | Systematic review/meta-analysis of 20 population-based studies; >30 million live births and ~12,000 spina bifida-affected infants (pqac-00000010, pqac-00000001) | IMR decreased 4.76% per 100,000 live births per year; infant case fatality decreased 2.70% per year; preterm birth RR 4.45 (2.30–8.60); low birthweight RR 4.77 (2.67–8.55) (pqac-00000010, pqac-00000001) | Ho et al., *PLOS ONE* 2021-05-12, DOI: 10.1371/journal.pone.0250098, https://doi.org/10.1371/journal.pone.0250098 (pqac-00000010, pqac-00000001) |
| Prevention / folate | Folic acid remains the most established preventive intervention for neural tube defects; mechanism linked to one-carbon metabolism and DNA methylation | Narrative review focused on Visegrad countries and broader NTD prevention literature (pqac-00000006) | FA supplementation during preconception/periconception reduces NTD incidence by nearly 80%; recommended dose 400 µg/day; folate deficiency may exceed 20% in many lower-income countries and is typically <5% in higher-income countries (pqac-00000006) | Rísová et al., *Nutrients* published 2024-12-31, DOI: 10.3390/nu17010126, https://doi.org/10.3390/nu17010126 (pqac-00000006) |
| Rehabilitation / function | Independence-focused rehabilitation evidence supports camp-based, CO-OP, occupation-based, self-catheterization, wheelchair, and assistive-tech interventions | Integrative review; 523 records screened, 19 met criteria, 18 intervention studies analyzed (pqac-00000008) | 18 intervention studies synthesized; strongest support reported for camp-based interventions, CO-OP, and occupation-based therapy to improve ADLs/IADLs independence (pqac-00000008) | Ferreira & Alves, *Cadernos Brasileiros de Terapia Ocupacional* 2024, DOI: 10.1590/2526-8910.ctoAR291837922, https://doi.org/10.1590/2526-8910.ctoAR291837922 (pqac-00000008) |
| Experimental therapy / trial | CuRe tests placenta-derived mesenchymal stem cells added to fetal repair to improve motor and autonomic outcomes beyond standard fetal surgery | Interventional Phase 1/2a clinical trial; estimated enrollment 55, recruiting; 35 treated + 20 contemporaneous non-PMSC cohort (pqac-00000021, pqac-00000022) | Primary endpoint: safety at birth (CSF leak, infection, wound healing failure, unexpected growth/tumor); secondary efficacy at 30 months includes motor improvement ≥2 levels over expected and independent walking, plus bowel/urologic outcomes (pqac-00000021, pqac-00000022) | ClinicalTrials.gov NCT04652908, first posted 2020-12-03; recruiting update verified 2026-01, https://clinicaltrials.gov/study/NCT04652908 (pqac-00000021, pqac-00000022) |


*Table: This compact evidence matrix summarizes high-value recent and foundational studies across genetics, prevention, surgery, prognosis, rehabilitation, and experimental therapy for spina bifida cystica/myelomeningocele. It is useful for rapidly mapping claims to quantitative evidence and source URLs.*