Association of MTHFR (C677T, A1298C) and MTRR A66G polymorphisms with fatty acids profile and risk of neural tube defects.

OBJECTIVE: This study aims to determine if 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms were associated with fatty acid (FA) levels in mothers of fetuses with neural tube defects (NTDs) and whether these associations were modified by environmental factors. METHODS: Plasma FA composition was assessed using capillary gas chromatography. Concentrations of studied FA were compared between 42 mothers of NTDs fetuses and 30 controls as a function of each polymorphism by the Kruskal-Wallis nonparametric test. RESULTS: In MTHFR gene C677T polymorphism, cases with (CT + TT) genotype had lower monounsaturated FAs (MUFA) and omega-3 polyunsaturated FA (n-3 PUFA) levels, but higher omega-6 polyunsaturated FAs (n-6 PUFA) and omega-6 polyunsaturated FAs: omega-3 polyunsaturated FAs (n-6:n-3) ratio levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype had lower MUFA levels, but higher PUFA and n-6 PUFA levels. Controls with (AG + GG) genotype had lower n-6 PUFA levels. In MTHFR gene C677T polymorphism, cases with smoking spouses and (CT + TT) genotype had lower MUFA and n-3 PUFA levels, but higher PUFA, n-6 PUFA, and n-6:n-3 ratio levels. Cases with (CT + TT) genotype and who used sauna during pregnancy had lower n-3 PUFA levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype and who used sauna during pregnancy had higher PUFA and n-6 PUFA levels. CONCLUSIONS: Further research is required to clarify the association of FA metabolism and (MTHFR, MTRR) polymorphisms with NTDs.

RSG1 is required for cilia-dependent neural tube closure.

Cilia play a key role in the regulation of signaling pathways required for embryonic development, including the proper formation of the neural tube, the precursor to the brain and spinal cord. Forward genetic screens were used to generate mouse lines that display neural tube defects (NTD) and secondary phenotypes useful in interrogating function. We describe here the L3P mutant line that displays phenotypes of disrupted Sonic hedgehog signaling and affects the initiation of cilia formation. A point mutation was mapped in the L3P line to the gene Rsg1, which encodes a GTPase-like protein. The mutation lies within the GTP-binding pocket and disrupts the highly conserved G1 domain. The mutant protein and other centrosomal and IFT proteins still localize appropriately to the basal body of cilia, suggesting that RSG1 GTPase activity is not required for basal body maturation but is needed for a downstream step in axonemal elongation.

The impact of a biocellulose-based repair of fetal open spina bifida on the need to untether the cord: is it time to unify techniques for prenatal repair?

OBJECTIVE: To report the need for cord untethering after prenatal repair of open spina bifida using a unique biocellulose-based technique performed at a later gestational age. METHODS: An observational cohort study was conducted to determine the incidence of tethered cord syndrome. Between May 2013 and May 2022, we performed 172 procedures using the percutaneous fetoscopic approach in fetuses at 26-28 weeks of gestation. After placode dissection, a biocellulose patch was placed to cover the placode, a myofascial flap (when possible) was dissected, and the skin was closed. Owing to death or loss to follow-up, 23 cases were excluded. Cord tethering syndrome was defined as symptoms of medullary stretching, and the infants were evaluated and operated on by local neurosurgeons after an magnetic resonance imaging examination. Infants over 30-month had ambulation and neurodevelopment evaluations (PEDI scale). RESULTS: Among 172 cases operated at a median gestational age of 26.7 weeks and delivered at 33.2 weeks, 149 cases were available for postnatal follow-up, and cord untethering was needed in 4.4% of cases (6/136; excluding 13 cases younger than 12 months). Cerebrospinal fluid diversion and bladder catheterization were needed in 38% and 36% of cases, respectively. Of the 78 cases evaluated at 30 months, 49% were ambulating independently, and 94% had normal social function. CONCLUSION: The biocellulose-based technique was associated with a low rate of cord tethering, wich may be attributed to the lack of the duramater suture during prenatal repair, the formation of a neoduramater and/or later gestational age of surgery.

Risk of meningomyelocele mediated by the common 22q11.2 deletion.

Meningomyelocele is one of the most severe forms of neural tube defects (NTDs) and the most frequent structural birth defect of the central nervous system. We assembled the Spina Bifida Sequencing Consortium to identify causes. Exome and genome sequencing of 715 parent-offspring trios identified six patients with chromosomal 22q11.2 deletions, suggesting a 23-fold increased risk compared with the general population. Furthermore, analysis of a separate 22q11.2 deletion cohort suggested a 12- to 15-fold increased NTD risk of meningomyelocele. The loss of Crkl, one of several neural tube-expressed genes within the minimal deletion interval, was sufficient to replicate NTDs in mice, where both penetrance and expressivity were exacerbated by maternal folate deficiency. Thus, the common 22q11.2 deletion confers substantial meningomyelocele risk, which is partially alleviated by folate supplementation.

Diagnosis and Management of Tethered Cord Syndrome.

Tethered cord syndrome is a condition in which the spinal cord is tethered by pathological structures such as a tight filum terminale, intradural lipomas with or without a connecting extradural component, intradural fibrous adhesions, diastematomyelia, and neural placode adhesions following closure of a myelomeningocele.It usually occurs in childhood and adolescence as the spine grows in length, but it can also develop in adulthood. Symptoms of tethered cord syndrome are slowly progressive and varied. Incorrect diagnosis and inappropriate treatment may be provided if the physician lacks knowledge and understanding of this disease.This chapter aims to describe the pathophysiology, syndromes, diagnostic imaging, surgical treatment, and prognosis of tethered cord syndrome to enhance the understanding of this condition.

Understanding perspectives on neural tube defect management: insights from Jordanian parents.

INTRODUCTION: Neural tube defects (NTDs) represent a spectrum of heterogeneous birth anomalies characterized by the incomplete closure of the neural tube. In Jordan, NTDs are estimated to occur in approximately one out of every 1000 live births. Timely identification of NTDs during the 18-22 weeks of gestation period offers parents various management options, including intrauterine NTD repair and termination of pregnancy (TOP). This study aims to assess and compare parental knowledge and perceptions of these management modalities between parents of affected children and those with healthy offspring. MATERIALS AND METHODS: This retrospective case-control study was conducted at Jordan University Hospital (JUH) using telephone-administered questionnaires. Categorical variables were summarized using counts and percentages, while continuous variables were analyzed using mean and standard deviation. The association between exposure variables and outcomes was explored using binary logistic regression. Data analysis was performed using SPSS for Windows version 26 (SPSS Inc., Chicago, IL). RESULTS: The study sample comprised 143 participants, with 49.7% being parents of children with NTDs. The majority of NTD cases were associated with unplanned pregnancies, lack of folic acid supplementation, and postnatal diagnosis. Concerning parental knowledge of TOP in Jordan, 86% believed it to be legally permissible in certain situations. However, there was no statistically significant difference between cases and controls regarding attitudes toward TOP. While the majority of parents with NTD-affected children (88.7%) expressed a willingness to consider intrauterine surgery, this percentage decreased significantly (to 77.6%) after receiving detailed information about the procedure's risks and benefits (p = .013). CONCLUSIONS: This study represents the first case-control investigational study in Jordan focusing on parental perspectives regarding TOP versus intrauterine repair of myelomeningocele following a diagnosis of an NTD-affected fetus. Based on our findings, we urge the implementation of a national and international surveillance program for NTDs, assessing the disease burden, facilitating resource allocation toward prevention strategies, and promoting early diagnosis initiatives either by using newly suggested diagnostic biomarkers or early Antenatal ultrasonography.

Inadvertent antibiotic exposure during pregnancy may increase the risk for neural tube defects in offspring.

BACKGROUND: As emerging environmental contaminants, antibiotics pose potential threats to human health, in particular to pregnant women and infants. However, the potential harm of inadvertent antibiotic exposure (IAE) is often disregarded in light of the focus on intentional antibiotic use during pregnancy. Currently, little is known about the effects of IAE during pregnancy on fetal neural tube development. METHODS: In this case-control study, we used questionnaire data from 855 subjects to investigate the effects of intentional antibiotic use in early pregnancy on neural tube defects (NTDs). Then we tested for placental antibiotics in mothers who had not intentionally used antibiotics, and the compounds were detected in 379 subjects; these were considered IAE cases. We assessed the association between IAE during pregnancy and fetal NTDs using both multivariable logistic and multi-pollutant exposure models. We also analyzed the correlation between maternal dietary habits and placental antibiotics to explore possible sources of IAE. RESULTS: Only 50 of 855 participants (5.8%) intentionally used antibiotics and such use showed no significant association with NTD risk (odds ratio [OR] = 1.92, confidence interval [95%CI] = [0.66, 5.59]). However, 14 of 15 placental antibiotics were detected in 378 of 379 subjects (99.7%) and multivariable logistic analysis indicated that high levels of placental macrolides were significantly associated with increased NTD risk (4.42 [2.01-10.45]). Multi-pollutant exposure analysis suggested an increase in NTD risk with an increase in exposure to a mixture of placental antibiotics, among which macrolides were the most important contributor. In addition, the level of placental macrolides was positively correlated with the intake frequency of milk. Finally, mothers who drank river, well, or pond water had higher levels of placental macrolides than those who drank only tap water. CONCLUSIONS: Intentional antibiotic use during early pregnancy may not be associated with NTDs, while IAE during pregnancy is associated with higher NTD risk in offspring. Macrolides are crucial risk factors. Milk, and river, well, or pond water may be important sources of IAE.

The Listeria monocytogenes persistence factor ClpL is a potent stand-alone disaggregase.

Heat stress can cause cell death by triggering the aggregation of essential proteins. In bacteria, aggregated proteins are rescued by the canonical Hsp70/AAA+ (ClpB) bi-chaperone disaggregase. Man-made, severe stress conditions applied during, e.g., food processing represent a novel threat for bacteria by exceeding the capacity of the Hsp70/ClpB system. Here, we report on the potent autonomous AAA+ disaggregase ClpL from Listeria monocytogenes that provides enhanced heat resistance to the food-borne pathogen enabling persistence in adverse environments. ClpL shows increased thermal stability and enhanced disaggregation power compared to Hsp70/ClpB, enabling it to withstand severe heat stress and to solubilize tight aggregates. ClpL binds to protein aggregates via aromatic residues present in its N-terminal domain (NTD) that adopts a partially folded and dynamic conformation. Target specificity is achieved by simultaneous interactions of multiple NTDs with the aggregate surface. ClpL shows remarkable structural plasticity by forming diverse higher assembly states through interacting ClpL rings. NTDs become largely sequestered upon ClpL ring interactions. Stabilizing ring assemblies by engineered disulfide bonds strongly reduces disaggregation activity, suggesting that they represent storage states.

Knowledge, awareness, and use of folic acid among women of childbearing age living in a peri-urban community in Ghana: a cross-sectional survey.

BACKGROUND: Folic acid, a water-soluble B-complex vitamin, plays a crucial role in DNA synthesis and maintenance, making it particularly significant during reproduction. Its well-known ability to reduce the risk of congenital anomalies during the periconceptional period underscores its importance. The increased requirement for folate during pregnancy and lactation is essential to support the physiological changes of the mother and ensure optimal growth and development of the foetus and offspring. This study assessed the knowledge, awareness, and use of folic acid among pregnant and lactating women of reproductive age residing in Dodowa in the Shai Osu-Doku District, Accra, Ghana. METHODS: The study was a cross-sectional design that involved 388 randomly selected participants (97 pregnant and 291 lactating women). Structured questionnaires were administered to gather information on the socioeconomic demographic characteristics, knowledge, awareness, and use of folic acid of the participants. Dietary intake was assessed using a food frequency questionnaire. The data were analysed using descriptive statistics and Pearson's chi-square analysis tests and are presented as frequencies and percentages, means, standard deviations, bar graphs, and pie charts. The significance of the results was determined at a 95% confidence interval. RESULTS: The mean age of the participants was 31 ± 5.0 years. Among the study participants, 46.1% demonstrated knowledge of folic acid deficiency, while approximately 68.3% had a high awareness of folic acid supplementation. Approximately 75% of the participants indicated that they had not used folic acid supplements within the week, and 15.5% reported consuming folic acid-fortified food per week. CONCLUSIONS: The women exhibited high awareness but poor knowledge regarding the usage of folic acid supplementation during pregnancy and lactation. Consequently, this lack of knowledge influenced the low use of folic acid supplements and low intake of folate-rich foods among pregnant and lactating mothers.

A Case Report of Fluoroscopically Guided Epidural Catheter Placement in a Parturient with History of Tethered Cord, Super-Morbid Obesity, and Risk for Difficult Airway.

Tethered cord syndrome results from adherence of the conus medullaris to the sacrum and may be associated with high complication rates from neuraxial anesthesia. We present the case of a 32-year-old gravida 2 para 0 patient with a history of lipomyelomeningocele (one of several types of spina bifida) and tethered cord status post repair, residual low-lying conus medullaris, supermorbid obesity (body mass index of 58), and Mallampati IV airway, who underwent successful fluoroscopically guided epidural catheter placement for vaginal delivery. Risks and benefits of epidural catheter utilization and methods of placement are reviewed.

Prevalence and associated factors of congenital anomalies in Ethiopia: A systematic review and meta-analysis.

BACKGROUND: Congenital anomalies represent a significant contributor to infant mortality, morbidity, and enduring disability. With this in mind, the present investigation endeavour to ascertain the pooled prevalence of congenital anomalies and associated determinants among neonates in Ethiopia. METHOD: PubMed, Google Scholar, CINAHAL, Hinari, and Global Health databases were systematically searched. Joanna Briggs Institute (JBI) assessment checklist was used to assess quality of included studies. Data were extracted from database and exported to stataMP-17 for analysis. Pooled prevalence was determined using DerSimonian-Laird random effects model. The degree of heterogeneity and Publication bias were assessed using I2 statistics and Eggers test, respectively. Study protocol was registered under PROSPERO ID CRD42021229140. RESULT: A total of 18 studies with 519,327 participants were included in the study. Pooled prevalence of congenital anomalies in Ethiopia was 2% (95% CI: 0.02, 0.03%). Among affected newborns neural tube defect (48%) was the most common congenital anomaly in Ethiopia, followed by orofacial cleft (19%). Risk factors such as alcohol consumption (pooled OR: 2.28, 95% CI: 1.54, 3.38), lack of folic acid supplement (pooled OR: 2.83, 95% CI: 1.09-7.36), medication during pregnancy (pooled OR: 2.58, 95% CI: 1.03-6.47), khat (Catha edulis) chewing (pooled OR: 2.44, 95% CI: 1.61-3.71), exposure to pesticides (pooled OR: 4.45, 95% CI: 2.44-8.09) and maternal illness (pooled OR:1.79, 95% CI: 1.03, 3.10) had statistically significant association with congenital anomalies in Ethiopia. CONCLUSION: In this review, prevalence of congenital anomalies in Ethiopia was high with considerable regional variation. The most common type of congenital anomaly in Ethiopia was neural tube defects, followed by oro-facial cleft. Alcohol consumption, inadequate intake of folic acid, khat chewing, maternal diseases, exposure to pesticides, and use of medication during pregnancy were identified as potential contributors to congenital abnormalities in Ethiopia.

Aberrant Dorsal Nerve Root as a Concomitant Cause of Spinal Cord Tethering Associated with a Dorsal Type Lipomyelomeningocele in a Child With Caudal Agenesis.

ABSTRACT: Tethered cord syndrome is a neurological disorder closely associated with congenital spinal dysraphism. Aberrant dorsal nerve roots may be one of the possible and relatively rare tethering pathologies, especially in the complex form of occult spinal dysraphism such as caudal regression syndrome or split cord malformation. We report an illustrative case of caudal regression syndrome with spinal cord tethering due to a combination of a contiguous bundle of an aberrant dorsal nerve root, and a dorsal-type lipomyelomeningocele, with a thickened filum terminale treated with microneurosurgical untethering.

Update on the impact of voluntary folic acid fortification of corn masa flour on red blood cell folate concentrations-National Health and Nutrition Examination Survey, 2011-March 2020.

BACKGROUND: Folic acid is a micronutrient that is effective at preventing neural tube defects (NTDs). In 2016, the FDA authorized the voluntary fortification of corn masa flour (CMF) with folic acid to reduce disparities in NTDs among infants of women who do not regularly consume other fortified cereal grains, in particular Hispanic women of reproductive age (WRA). METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to March 2020 assessing the impact of voluntary fortification of CMF on the folate status of Hispanic WRA. We analyzed folic acid usual intake and red blood cell (RBC) folate concentrations among non-pregnant, non-lactating Hispanic WRA, comparing pre-fortification (2011-2016) to post-fortification (2017-March 2020) data. RBC folate concentrations were used to create model-based estimation of NTD rates. RESULTS: The proportion of Hispanic WRA with folic acid usual intakes <400 µg/d did not change (2011-2016: 86.1% [95% Confidence Interval, CI: 83.7-88.5]; 2017-March 2020: 87.8% [95% CI: 84.8-90.7]; p = .38) nor did the proportion of Hispanic WRA with RBC folate below optimal concentrations (<748 nmol/L, 2011-2016: 16.0% [95% CI: 13.7-18.2]; 2017-March 2020: 18.1% [95% CI: 12.1-24.0]; p = 0.49). Model-based estimates of NTD rates suggest further improvements in the folate status of Hispanic WRA might prevent an additional 157 (95% Uncertainty Interval: 0, 288) NTDs/year. CONCLUSIONS: Voluntary fortification of CMF with folic acid has yet to have a significant impact on the folate status of WRA. Continued monitoring and further research into factors such as fortified product availability, community knowledge, and awareness of folic acid benefits would inform and improve future public health interventions.

Folic Acid-Fortified Iodized Salt and Serum Folate Levels in Reproductive-Aged Women of Rural India: A Nonrandomized Controlled Trial.

Importance: India has a disproportionately high prevalence of neural tube defects, including spina bifida and anencephaly (SBA), causing a high number of stillbirths, elective pregnancy terminations, and child mortality; India contributes a large proportion of the global burden of SBA. Thirty years after folic acid was shown to be effective in reducing SBA prevalence, only about one-quarter of such births are prevented globally through cereal grain fortification. Objective: To determine the association of folic acid-fortified iodized salt with serum folate concentrations among nonpregnant and nonlactating women of reproductive age. Design, Setting, and Participants: This nonrandomized controlled trial using a preintervention and postintervention design was conducted in 4 rural villages in Southern India from July 1 to November 30, 2022. All households in the villages agreed to participate in the study. Preintervention and postintervention serum folate levels were analyzed among study participants at baseline and after 4 months, respectively. Intervention: Consumption of approximately 300 µg/d of folic acid using double fortified salt (folic acid plus iodine). Median serum folate concentrations were assessed at baseline and 4 months. Main Outcomes and Measures: Change in median serum folate levels between baseline and study end point as the primary outcome of the study. Results: A total of 83 nonpregnant nonlactating women aged 20 to 44 years (mean [SD] age, 30.9 [5.1] years) were eligible for the study and provided serum samples for analysis at baseline and the end point of the intervention. The median serum folate concentration increased from 14.6 (IQR, 11.2-20.6) nmol/L at baseline to 54.4 (IQR, 43.5-54.4) nmol/L at end of study, a 3.7-fold increase from baseline to study end point. Two-tailed Wilcoxon signed rank test showed the median difference in preintervention and postintervention serum folate concentrations to be highly significant (P < .001). The participants found the salt acceptable in color and taste. Conclusions and Relevance: Use of folic acid-fortified iodized salt was associated with increased serum folate concentrations in women of reproductive age. This novel evidence can inform public health policy to accelerate SBA prevention. Trial Registration: ClinicalTrials.gov Identifier: NCT06174883.

Perspectives on folate with special reference to epigenetics and neural tube defects.

Folate is a micronutrient essential for DNA synthesis, cell division, fetal growth and development. Folate deficiency leads to genomic instability. Inadequate intake of folate during conception may lead to neural tube defects (NTDs) in the offspring. Folate influences the DNA methylation, histone methylation and homocysteine mediated gene methylation. DNA methylation influences the expression of microRNAs (miRNAs). Folate deficiency may be associated with miRNAs misregulation leading to NTDs. Mitochondrial epigenetics and folate metabolism has proved to be involved in embryogenesis and neural tube development. Folate related genetic variants also cause the occurrence of NTDs. Unmetabolized excessive folate may affect health adversely. Hence estimation of folate levels in the blood plays an important role in high-risk cases.

Association of spinal cord abnormalities with vertebral anomalies: an embryological perspective.

PURPOSE: To analyze the relationship between spinal cord and vertebral abnormalities from the point of view of embryology. METHODS: We analyzed the clinical and radiological data of 260 children with different types of spinal cord malformations in combination with vertebral abnormalities. RESULTS: Among 260 individuals, approximately 109 presented with open neural tube defects (ONTDs), 83 with split cord malformations (SCMs), and 83 with different types of spinal lipomas. Pathological spina bifida emerged as the most frequent vertebral anomaly, affecting 232 patients, with a higher prevalence in ONTD. Vertebral segmentation disorders, including unsegmented bars, butterfly vertebrae, and hemivertebrae, were present in 124 cases, with a higher prevalence in SCM. The third most common spinal anomaly group consisted of various forms of sacral agenesis (58 cases), notably associated with blunt conus medullaris, spinal lipomas, and sacral myelomeningocele. Segmental aplasia of the spinal cord had a typical association with segmental spinal absence (N = 17). CONCLUSION: The association between SCM and neuroenteric cyst/canal and vertebral segmentation disorders is strong. High ONTDs often coincide with pathological spina bifida posterior. Type 1 spinal lipomas and focal spinal nondisjunction also correlate with pathologic spina bifida. Segmental spinal absence or dysgenesis involves localized spinal and spinal cord aplasia, sometimes with secondary filar lipoma.

Prognostic Significance of Central Skull Base Remodeling in Chiari II Malformation.

BACKGROUND AND PURPOSE: Outward convexity of the basiocciput and posterior atlanto-occipital membrane are common in patients with Chiari II malformation associated with an open neural tube defect. We aimed to determine if the severity of these findings correlated with the need for future hydrocephalus treatment. MATERIALS AND METHODS: A retrospective chart and imaging review identified patients who underwent open neural tube defect repair at a quaternary care pediatric hospital from July 2014 through September 2022. Patients were classified by the need for hydrocephalus treatment and whether they received prenatal or postnatal neural tube defect repair. Measurements of imaging parameters related to posterior fossa maldevelopment and skull base remodeling were performed. RESULTS: Compared with 65 patients who did not require hydrocephalus treatment, 74 patients who required treatment demonstrated statistically significantly greater mean basiocciput convexity (P < .001). While the mean basiocciput length in the hydrocephalus treatment group was smaller (P < .001), the ratio of basiocciput convexity to length was larger (P < .001). Notably, 100% of patients with a basiocciput convexity of ≥4 mm required hydrocephalus treatment. The mean posterior atlanto-occipital membrane convexity was significantly greater for patients who required hydrocephalus treatment in the postnatal group (P = .02), but not the prenatal group (P = .09). CONCLUSIONS: Pediatric patients with Chiari II malformation who ultimately required surgical hydrocephalus treatment had greater outward convexity of the basiocciput but had greater posterior atlanto-occipital membrane outward convexity only if the repair was performed postnatally. Together these measurements may be useful in predicting the need for hydrocephalus treatment.

Folate and vitamin B12 status and predicted neural tube defects risk among nonpregnant women of reproductive age from the Malawi National Micronutrient Survey, 2015-2016.

BACKGROUND: Maternal folate and vitamin B12 deficiency can lead to serious adverse pregnancy outcomes. There are no nationally representative estimates on folate and vitamin B12 status among women of reproductive age (WRA) in Malawi. OBJECTIVE: We assessed folate and vitamin B12 status among nonpregnant WRA in Malawi and predicted the risk of folate-sensitive neural tube defects (NTDs) were they to become pregnant. METHODS: Using data from the cross-sectional, nationally representative 2015-2016 Malawi Micronutrient Survey, we calculated the proportion of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 778 nonpregnant WRA (15-49 years). We predicted NTD prevalence using red blood cell (RBC) folate distributions and a published Bayesian model of the association between RBC folate and NTD risk. Analyses accounted for complex survey design. RESULTS: Among WRA, 8.5% (95% CI: 6.2, 11.6) and 13.3% (10.0, 17.4) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The proportion of vitamin B12 deficiency (<148 pmol/L) and insufficiency (≤221 pmol/L) was 11.8% (8.6, 16.0) and 40.6% (34.1, 47.4), respectively. RBC folate insufficiency (<748 nmol/L, defined as the concentration associated with the threshold for elevated NTD risk: >8 cases per 10,000 births) was widespread: 81.4% (75.0, 86.4). The predicted NTD risk nationally was 24.7 cases per 10,000 live births. RBC folate insufficiency and higher predicted NTD risk were more common among WRA living in urban areas or with higher education. CONCLUSIONS: These findings highlight the importance of nutritional and NTD surveillance in Malawi and the opportunity for improving folate and vitamin B12 nutrition among Malawian WRA.

Genome-wide analysis of spina bifida risk variants in a case-control study from Bangladesh.

BACKGROUND: Human studies of genetic risk factors for neural tube defects, severe birth defects associated with long-term health consequences in surviving children, have predominantly been restricted to a subset of candidate genes in specific biological pathways including folate metabolism. METHODS: In this study, we investigated the association of genetic variants spanning the genome with risk of spina bifida (i.e., myelomeningocele and meningocele) in a subset of families enrolled from December 2016 through December 2022 in a case-control study in Bangladesh, a population often underrepresented in genetic studies. Saliva DNA samples were analyzed using the Illumina Global Screening Array. We performed genetic association analyses to compare allele frequencies between 112 case and 121 control children, 272 mothers, and 128 trios. RESULTS: In the transmission disequilibrium test analyses with trios only, we identified three novel exonic spina bifida risk loci, including rs140199800 (SULT1C2, p = 1.9 × 10-7), rs45580033 (ASB2, p = 4.2 × 10-10), and rs75426652 (LHPP, p = 7.2 × 10-14), after adjusting for multiple hypothesis testing. Association analyses comparing cases and controls, as well as models that included their mothers, did not identify genome-wide significant variants. CONCLUSIONS: This study identified three novel single nucleotide polymorphisms involved in biological pathways not previously associated with neural tube defects. The study warrants replication in larger groups to validate findings and to inform targeted prevention strategies.