Neural Tube Defects Research Articles

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

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. 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. 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. Further research is required to clarify the association of FA metabolism and (MTHFR, MTRR) polymorphisms with NTDs.

A retrospective study of congenital anomalies and associated risk factors among children admitted at a tertiary hospital in northwestern Tanzania.

Congenital anomalies in Sub-Sahara Africa (SSA) are understudied despite the significant pediatric health burden. This retrospective longitudinal hospital-based study evaluated the records of 326 inpatient children under the age of two years with congenital anomalies at Bugando Medical Centre, a tertiary referral hospital in northwestern Tanzania. Classical logistic regression was used in the analysis of congenital malformation of muscles, gastrointestinal malformation, oral facial clefts, neural tube defects, and skeletal malformations. A modified poisson regression was used to model risk factors for Central Nervous System (CNS) hydrocephalus and congenital heart disease (CHD). A majority (78.8%) of children included in the study were less than six months of age. Nearly half (48.8%) were diagnosed with CHD followed by CNS hydrocephalus (10.4%) and congenital malformation of muscles (8.9%). Babies whose mothers missed periconceptual folic acid supplementation had 83% higher risk of hydrocephalus (aPR = 1.83, 95% CI = 1.11-1.96) and 78% higher for CHD (aPR = 1.78, 95% CI = 1.31-1.94). Male children had 1.67 higher odds of muscular congenital malformations (aOR = 1.67, 95% CI = 1.23-1.89). Less than 37 gestational age had a 1.86 higher odds of muscular congenital malformations (aOR = 1.86, 95% CI = 1.53-3.66). Our study highlights the critical need for folic acid supplementation and establishes a need for a registry and the potential for mapping.

Perinatal Management of Pregnancies with Fetal Congenital Anomalies: A Guide to Obstetricians and Pediatricians.

Congenital anomalies are responsible for approximately 20% of all neonatal deaths worldwide. Improvements in antenatal screening and diagnosis have significantly improved the prenatal detection of birth defects; however, these improvements have not translated into the improved neonatal prognosis of babies born with congenital anomalies. An attempt has been made to summarise the prenatal interventions, if available, the optimal route, mode and time of delivery and discuss the minimum delivery room preparations that should be made if expecting to deliver a fetus with a congenital anomaly. The recent literature related to the perinatal management of the fetus with prenatally detected common congenital anomalies was searched in English peer-reviewed journals from the PubMed database to work out an evidence-based approach for their management. Fetuses with prenatally detected congenital anomalies should be delivered at a tertiary care centre with facilities for neonatal surgery and paediatric intensive care if needed. There is no indication for preterm delivery in the majority of cases. Only a few congenital malformations, like highrisk sacrococcygeal teratoma, congenital lung masses with significant fetal compromise, fetal cerebral lesions or neural tube defects with Head circumference >40 cm or the biparietal diameter is ≥12 cm, gastroschisis with extracorporeal liver, or giant omphaloceles in the fetus warrant caesarean section as the primary mode of delivery. The prognosis of a fetus with congenital anomalies can be significantly improved if planning for delivery, including the place and time of delivery, is done optimally. A multidisciplinary team should be available for the fetus to optimize conditions right from when it is born.

Serum pcsk9 levels as a novel biomarker for pregnant women with risk of fetal neural tube defects

Serum pcsk9 levels as a novel biomarker for pregnant women with risk of fetal neural tube defects

Brief title of the study case report: a case of type II sacral agenesis with no neurogenic dysfunction

BackgroundSacral agenesis is a rare neural tube defect characterized by abnormal development of the caudal aspect of the vertebral column and the spinal cord. Even though the etiology is unknown. Its pathophysiology has been linked to maternal diabetes, genetic factors, and several teratogens.Case reportThis case report presents the case of a young female patient (2 years old) of sacral agenesis type II with no neurogenic dysfunctions. MRI results were specifically used to make the diagnosis. There were no anatomical or functional impairments found in this patient, making the presentation of this case unique.ConclusionsThe case is being reported for its rarity and educational value because the prognosis is good in isolated sacral agenesis. Early detection and prompt treatment are crucial to decreasing the risk of complications and improving the prognosis.

Management of giant posterior meningocele lombosacral: about three case report

Meningoceles are one of the most common malformations of the nervous system, accounting for around 10% of all neural tube defects. It is a complex congenital malformation of the spine, characterized by protrusions or expansions of one or more layers of the thecal sac through a canal or foramen of the spine in which there is a defect. Children usually show no neurological signs at birth, but surgical exploration is warranted to prevent future neurological deterioration. These malformations are frequently found in a posterior position, with dysraphic vertebrae in the lumbosacral region. Their management is associated with multiple challenges in our regions, including difficulties with perioperative and anesthetic care. We report these to highlight and share our experiences in the perioperative management of meningocele.

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

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. 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. 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. 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.

Bladder height to width ratio as a surrogate marker for non-physiological storage pressures in children with spinal dysraphism.

Spinal dysraphism is the most frequent cause of neurogenic bladder. Urodynamic study (UDS) is an important component of the follow-up of a child with neurogenic bladder. However, it suffers from a lack of widespread availability and is further hampered by technical difficulties and difficulty in its interpretation in children. A neurogenic bladder often appears vertically elongated; only limited and sparse literature is available regarding objectively defining the bladder shape and the urodynamic parameters in the cohort. This study aimed to investigate the usefulness of the bladder's height-to-width ratio (HWR) on cystogram as a screening tool for identifying "non-physiological" bladder pressures in children with spinal dysraphism. A prospective study was undertaken to evaluate children operated for spinal dysraphism. Cystogram, ultrasonography and UDS evaluation were performed. HWR was calculated by the ratio of the maximum height to the maximum bladder width at maximum cystometric capacity (MCC), where MCC was calculated using standard Koff's formula, given by (age in years + 2) *30ml in children more than one year and weight *7ml for infants. The children were categorised into groups based on maximum detrusor pressure (MDP) into two groups (MDP ≥ 30cmH2O and MDP < 30cmH2O). A receiver-operative characteristic curve was constructed to analyse the sensitivity and specificity of HWR in predicting the MDP. A total of 53 children, operated for spinal dysraphism, met the study criteria during the study period, from March 2021 to September 2022. The median age of children was 4years (IQR-3-5.5years). The HWR ratio was compared between the two groups and was significantly higher for the non-physiological pressure bladders than for physiological pressure bladders (mean of 1.55 vs 1.26, p = 0.001). On evaluating the sensitivity and specificity of HWR for discerning children with non-physiological bladder pressures were 87.5% and 48.28%, respectively. The area under the curve (AUC) was 0.781, with a cut-off value of 1.3. We attempted to evaluate the HWR based on bladder shape objectively. We demonstrated a moderate correlation between the bladder shape and the bladder pressures. An HWR of 1.3 or higher could be significant for identifying a non-physiological bladder storage pressure. The height to width ratio of the bladder on cystogram is a useful tool as a surrogate marker for non-physiological storage pressures in bladders of children with spinal dysraphism.

Cartilage within lipomyelomeningocele and ulnar longitudinal deficiency syndrome as VACTERL association, alliance in SHH/GLI3, and Wnt pathway: illustrative case.

Lipomyelomeningocele associated with an ulnar club hand in the spectrum of VACTERL association ([costo-]vertebral abnormalities; anal atresia; cardiac defects; tracheal-esophageal abnomalities, including atresia, stenosis, and fistula; renal and radial abnormalities; limb abnormalities; single umbilical artery) is a very rare and infrequently reported phenomenon. Within the fat mass of the lipoma, it is not common to find a well-defined cartilaginous mass with no attachments to the surrounding tissue. The authors present the case of a 3-month-old male with low-back swelling that was off-center to the left, accompanied by a left short forearm displaying outward bowing. Echocardiography showed an atrial septal defect. This rare VACTERL association comprises lipomyelomeningocele, atrial septal defect, and ulnar longitudinal deficiency syndrome. During surgical intervention for the lipoma, a well-defined cartilaginous mass was discovered within the adipose tissue. The manifestation of VACTERL association can be partially explained by the Shh/Gli and Wnt pathway defects. It is prudent to screen children with neural tube defects to be aware of any associated syndromes. This case is very rare, and the literature has contained no prior report on the VACTERL association of lipomyelomeningocele, atrial septal defect, and ulnar longitudinal deficiency.

Periventricular nodular heterotopia in patients with a prenatal diagnosis of myelomeningocele/myeloschisis: associations with seizures and neurodevelopmental outcomes during early childhood.

Historically, the presence of gray matter heterotopia was a concern for adverse postnatal neurocognitive status in patients undergoing fetal closure of open spinal dysraphism. The purpose of this study was to evaluate neurodevelopmental outcomes and the onset of seizures during early childhood in patients with a prenatal diagnosis of myelomeningocele/myeloschisis (MMC) and periventricular nodular heterotopia (PVNH). All patients evaluated at the Center for Fetal Diagnosis and Treatment with a diagnosis of MMC between June 2016 to March 2023 were identified. PVNH was determined from prenatal and/or postnatal MRI. The Bayley Scales of Infant and Toddler Development (edition III or IV) were used for neurodevelopmental assessments. Patients were screened for seizures/epilepsy. Of 497 patients evaluated with a prenatal diagnosis of MMC, 99 were found to have PVNH on prenatal MRI, of which 35 had confirmed PVNH on postnatal imaging. From the 497 patients, 398 initially did not exhibit heterotopia on prenatal MRI, but 47 of these then had confirmed postnatal PVNH. The presence of PVNH was not a significant risk factor for postnatal seizures in early childhood. The average neurodevelopmental scores were not significantly different among heterotopia groups for cognitive, language, and motor domains. The presence of PVNH in patients with a prenatal diagnosis of MMC does not indicate an increased risk for neurodevelopmental delay at 1year of age. We did not demonstrate an association with seizures/epilepsy. These findings can aid clinicians in prenatal consultation regarding fetal repair of open spinal dysraphism. Long-term follow-up is required to discern the true association between PVNH seen on prenatal imaging and postnatal seizures/epilepsy and neurodevelopmental outcomes.

Different fetal effects on fingers from exposure to phenytoin, phenobarbital, and carbamazepine.

Exposure at conception to phenytoin (PHT), phenobarbital (PB), and carbamazepine (CBZ) has been associated with several different effects on the fetus, including hypoplasia of the distal phalanges, dysmorphic facial features, and structural abnormalities such as oral clefts and neural tube defects. One question is whether each of these antiepileptic drugs (AEDs) has the same effects or just similar effects. A systematic examination of the fingers of children exposed at conception to PHT, PB, or CBZ, as monotherapy, has been used to address this question. The findings in the examinations of the fingers of 115 AED-exposed children (40, PHT; 34, PB; 41, CBZ) and their parents were compared to the findings in 111 age- and sex-matched children and their parents. The evaluations used were both subjective assessments and objective measurements. Shortening and narrowing of the fifth fingernail and an increased frequency of arch patterns in the dermal ridges were more common in PHT-exposed children. A significant decrease in the length of the nail, but not width, occurred in the PB-exposed children. Stiffness of the interphalangeal joints was more common in the CBZ-exposed children. The findings in children exposed to PHT, PB, or CBZ, as monotherapy, showed that all three exposures in early pregnancy affected the fingers, but the effects were not the same. The most striking effects were present in PHT-exposed children.

Anencephaly: A case report and the crucial role of folic acid supplementation and early diagnosis

Anencephaly is a congenital malformation caused by neural tube failure, which can be managed through folic acid intake during pregnancy. Diagnosis is typically prenatal, and termination of pregnancy is often recommended. A newborn born at Kolwezi paediatric clinic was born with a visible congenital malformation. The mother had a low socio-economic background and was 41 years old. An ultrasound scan revealed a progressing pregnancy at 30 weeks gestation with polyhydramnios. No antenatal care monitoring or folic acid prophylaxis was implemented during the periconceptional period and throughout the pregnancy. Anencephaly diagnosis was confirmed, and the newborn died five minutes post-birth. Preventive folic acid treatment has shown a decrease in neural tube defects, and first-trimester ultrasound scans can help identify life-incompatible congenital malformations. Advocating for legislative measures and genetic counselling is crucial to educate parents on recurrence risks and the advantages of folic acid supplementation before subsequent pregnancies.

Socioeconomic profile of families with spina bifida children in Turkey

BackgroundSpina bifida’s prevalence and incidence vary across geographical regions with sociodemographic characteristics and socioeconomic status of the populations having a significate influence over its epidemiology. This study aimed to outline the socioeconomic profile of families with spina bifida children, based on sociodemographic characteristics.MethodsBetween August and December 2022, 86 surveys completed by parents of children that underwent spina bifida repair in our institution were included in this analysis. The first part of the survey included questions based on sociodemographic characteristics. The second part of the survey was based on care provided by the families, regular follow-ups, participation in rehabilitation programs, and type of burdens perceived by the caregivers.ResultsA close look at the highest level of parent education showed that more than half of them were only middle school graduates. Occupational status in the perioconceptional period revealed that 77% of mothers were housewives/unemployed. 23% had a history of induced or spontaneous abortion. A high number of consanguine marriages were registered with 58% of the subjects being biologically related. 53% of the spina bifida children came from families with low household income. Only 15% of the spina bifida children had access to physiotherapy and 18% to rehabilitation programs.ConclusionsChildren with spinal dysraphism were more likely to come from families resulted from consanguineous marriages, with at least two children, low level of parent education and household income. Emotional and financial burden perceived by caregivers should be addressed in order to diminish the numerous challenges that this group of families encounter.

Sleep-related breathing disorders in infants with spina bifida repaired prenatally and postnatally.

Advances in prenatal repair of myelomeningocele (MMC) have improved outcomes involving different organ systems. There is limited data on respiratory outcomes following prenatal surgical repair. We hypothesize there is no difference in respiratory outcomes between spina bifida (SB) patients who have undergone prenatal versus postnatal repair. We performed a retrospective study of 46 infants <1 year with SB seen at Children's Hospital Los Angeles from 2004-2022. Demographic data, timing of closure, neonatal course, Chiari II malformation (CIIM), ventriculoperitoneal shunt (VPS), polysomnography (PSG) results, and need for supplemental oxygen were collected. Unpaired t-test and Chi-square Test were used to analyze results. 31/46 had prenatal repair of MMC; average age at repair was 27 weeks post-conception (PCA). Average age at postnatal repair was 37 PCA. There was no difference in age at PSG. There was no difference in CIIM presence (p=0.61). 60% of patients with postnatal repair and 23% in the prenatal group underwent VPS placement (p=0.01). Patients with SB who've undergone closure of neural tube defect have persistent central apneas, obstructive apneas, and significant hypoxemia. There were no differences in the frequency or severity of sleep-disordered breathing in those with prenatal repair versus postnatal repair.

The Effect of In-vitro Fertilization Procedures on Alpha-fetoprotein Levels in Second Trimester Screening for Fetal Defects

Objective Prenatal screening for developmental and chromosomal fetal defects during both the first and second trimesters of pregnancy is considered standard practice. In the second trimester, screening for spinal cord malformations, such as spina bifida and anencephaly (a type of neural tube defect), involves measuring alpha-fetoprotein levels in maternal blood. The cutoffs used to identify increased risks for neural tube defects are typically tailored for factors like race, multiple fetuses, reported smoking, and the presence of maternal insulin-dependent diabetes. What remains unclear is the impact of assisted reproductive technology, commonly known as in vitro fertilization procedures, on alpha-fetoprotein levels and other measured analytes. Method This report presents a retrospective study that examines the impact of reported in vitro fertilization procedures on second-trimester levels of alpha-fetoprotein. The study utilizes consecutive data from March 20, 2019, through March 29, 2023, sourced from laboratory records. Result We illustrate elevated levels of maternal serum alpha-fetoprotein across all racial subgroups undergoing in vitro fertilization procedures. Additionally, we demonstrate that maternal serum alpha-fetoprotein levels rise with maternal age. Conclusion This study underscores the significance of our findings in evaluating the risk of neural tube defects, such as spina bifida, Down syndrome, and other genetic anomalies. It holds considerable value in guiding clinical practices. Furthermore, it highlights the need for further investigation to evaluate how our findings impact the assessment of fetal well-being.

Pediatric Lower Urinary Tract Dysfunction: A Comprehensive Exploration of Clinical Implications and Diagnostic Strategies.

Lower urinary tract dysfunction is clinically important because it may cause urinary tract infections, mainly due to accumulation of residual urine, and adversely affect renal function. In addition, it may cause urinary incontinence, strongly affecting the child's quality of life. The function of the lower urinary tract is closely associated with function of the bowel because constipation is commonly present with bladder dysfunction. The interplay between the lower urinary tract and bowel function, coupled with common conditions such as detrusor overactivity and voiding dysfunction, requires a nuanced diagnostic approach. Detrusor overactivity, a benign but socially harmful condition, is the principal cause of daytime urinary incontinence in childhood. It needs to be differentiated from more serious conditions such as neurogenic bladder dysfunction or urethral obstruction. Voiding dysfunction, a habitual sphincter contraction during voiding, is common in children with detrusor overactivity and may be self limiting but may also result in residual urine and urinary tract infections. It may resemble, in severe cases, neurogenic bladder dysfunction, most often caused by spinal dysraphism, which very often leads to recurrent urinary tract infections and high intravesical pressures, jeopardizing renal function. A voiding diary is crucial in the initial evaluation of lower urinary tract function in children.

Dolutegravir and Folic Acid Interaction during Neural System Development in Zebrafish Embryos.

Dolutegravir (DTG) is one of the most prescribed antiretroviral drugs for treating people with HIV infection, including women of child-bearing potential or pregnant. Nonetheless, neuropsychiatric symptoms are frequently reported. Early reports suggested that, probably in relation to folic acid (FA) shortage, DTG may induce neural tube defects in infants born to women taking the drug during pregnancy. Subsequent reports did not definitively confirm these findings. Recent studies in animal models have highlighted the association between DTG exposure in utero and congenital anomalies, and an increased risk of neurologic abnormalities in children exposed during in utero life has been reported. Underlying mechanisms for DTG-related neurologic symptoms and congenital anomalies are not fully understood. We aimed to deepen our knowledge on the neurodevelopmental effects of DTG exposure and further explore the protective role of FA by the use of zebrafish embryos. We treated embryos at 4 and up to 144 h post fertilization (hpf) with a subtherapeutic DTG concentration (1 μM) and observed the disruption of the anterior-posterior axis and several morphological malformations in the developing brain that were both prevented by pre-exposure (2 hpf) and rescued by post-exposure (10 hpf) with FA. By whole-mount in situ hybridization with riboprobes for genes that are crucial during the early phases of neurodevelopment (ntl, pax2a, ngn1, neurod1) and by in vivo visualization of the transgenic Tg(ngn1:EGFP) zebrafish line, we found that DTG induced severe neurodevelopmental defects over time in most regions of the nervous system (notochord, midbrain-hindbrain boundary, eye, forebrain, midbrain, hindbrain, spinal cord) that were mostly but not completely rescued by FA supplementation. Of note, we observed the disruption of ngn1 expression in the dopaminergic regions of the developing forebrain, spinal cord neurons and spinal motor neuron projections, with the depletion of the tyrosine hydroxylase (TH)+ dopaminergic neurons of the dorsal diencephalon and the strong reduction in larvae locomotion. Our study further supports previous evidence that DTG can interfere with FA pathways in the developing brain but also provides new insights regarding the mechanisms involved in the increased risk of DTG-associated fetal neurodevelopmental defects and adverse neurologic outcomes in in utero exposed children, suggesting the impairment of dopaminergic pathways.

Spinal Intradural Epidermoid Cyst with Dermal Sinus in a 2 – Year Old Child: A Rare Case Report

Introduction: Spinal epidermoid accounts for &lt; 1% of all primary cord tumor. This rare benign lesion may be congenital or acquired. Invagination of epidermal elements into the neural tube during embryonic period leads to the development of epidermoid cyst. Case Presentation: A 2 year old girl presented with a spontaneous intergluteal swelling with dermal sinus and lower limbs weakness. The lumber MR demonstrated an intradural lesion from L3 to L5 levels that compressed cauda equine or nerve roots. MR findings were compatible with an epidermoid cyst with dermal sinus without any coexistent spinal dysraphism. The patient underwent microsurgical laminectomy from L3 to L5, tumor was resected and sent for histopathological examination. A pearly white tumor was found and histopathology revealed an epidermoid tumor. Post-operative Magnetic Resonance Imaging (MRI) finding was total removal. Conclusion: Diagnosis of spinal epidermoid cyst is often delayed due to its obscure presentation. Here, we presented spinal lumber intradural epidermoid cyst with dermal sinus which was treated successfully with microsurgical total resection with preservation of spinal stability and neurological function. Post-operative follow up with MRI is helpful.

DTYMK is an essential gene in mice and heterozygosity does not cause neural tube defects

Regulation of nucleotide biosynthesis is necessary for maintaining cellular processes including DNA replication and repair. A key enzyme in this process is deoxythymidylate kinase (dTYMK), which catalyzes the initial step in the production of dTTP from dTMP. This gene constitutes the first merged step of dTTP synthesis from the de novo and salvage pathways which regulate dTMP biosynthesis. Decreased de novo dTMP biosynthesis causes dysregulated dTTP:dUTP pools, and leads to increased uracil in DNA and neural tube closure defect (NTD) development in mice. The goal of this research was to investigate if dTYMK, the downstream enzyme in dTTP production, is an essential gene in mice and if impairments in dTYMK play a causal role in development including NTD pathology in mice. Dtymk+/− C57BL/6J females were weaned onto either a control, excess folic acid, or folic acid deficient diet and timed breeding was performed after 8 weeks on diet. The offspring were analyzed for NTDs and other reproductive outcomes at embryonic day 12.5 (E12.5). Dtymk–/– mice were confirmed to be embryonic lethal before E12.5, and Dtymk+/− mice on all three experimental diets did not show the presence of open neural tube defects, spina bifida or exencephaly. However, the expression of dTYMK in Dtymk+/− mouse embryos was confirmed to be decreased by approximately 3-fold compared to Dtymk+/+ embryos. Although dTYMK was demonstrated to be an essential gene in mice and is required for the regulation of nucleotide pools in vitro, there was no evidence of increased risk of NTDs because of a reduction in expression of this enzyme during embryonic development. It is possible that a further reduction in expression may be required to see developmental anomalies in C57BL/6J mice.

Prevalence and Risk Factors for Congenital Malformations in Morocco

Background: Congenital malformations are among the most pressing health concerns globally. In Morocco, minimizing the morbidity and mortality associated with congenital malformations is a key health policy objective. In the Marrakech-Safi region, the prevalence and etiology of congenital malformations remain unclear. Objectives: This study seeks to ascertain the prevalence of clinically evident congenital malformations and identify the factors contributing to their incidence in the Marrakech-Safi region. Methods: A retrospective study was conducted in the maternity ward of the Mohamed VI University Hospital Center in Marrakech in 2022. An obstetric chart was utilized to gather sociodemographic, obstetrical, maternal, and neonatal data from the target population, including risk factors. The data were analyzed using SPSS 21 software. Results: Out of 17 250 files reviewed, 159 births with malformations were identified, resulting in a prevalence of 0.92% of births. Newborns with multiple malformations constituted 22.64% of all cases, with a prevalence of 2.08/1000 births. Neural tube defects were the most common, with a prevalence of 3.65/1000 births, followed by musculoskeletal defects and digestive tract defects. Chromosomal malformations, specifically trisomy 21, were the fifth most common, with a prevalence of 1.4/1000 births. Facial and urogenital malformations were the least frequent in this study. The occurrence of congenital malformations in this region is influenced by various risk factors, including maternal age, male sex, parity, medical history, and newborn weight at birth. Conclusions: In the Marrakech-Safi region, congenital malformations are influenced by a wide range of risk factors. Identifying these factors is crucial for healthcare providers to enhance surveillance among at-risk populations and develop effective preventive, diagnostic, and therapeutic strategies.