Prevention Of Neural Tube Defects Research Articles

Perikoncepcijska primena folne kiseline kod trudnica u Bosni i Hercegovini - studija preseka

Folic acid (FA) supplementation is recommended for all women of childbearing age and pregnant women. Still, women's adherence to these recommendations is often low. This crosssectional survey aimed to assess FA supplementation among pregnant women in Bosnia and Herzegovina (BiH) since no such data exist to date. Data were collected by a voluntary, anonymous, self-administered internet-based questionnaire. The inclusion criteria were current pregnancy, BiH origin, and BiH residence for at least the past 5 years. The vast majority (82.1%) of women reported inadequate periconceptional FA supplementation, and only 26.9% reported supplementation during the critical period for neural tube closure. The use of a high dose (≥5 mg/day) FA beyond the first trimester was reported by 9.0% of women. Women's age was significantly associated with adequate folic acid use for the prevention of neural tube defects (OR=1.207, p<0.05). The periconceptional FA supplementation in the studied population is suboptimal. These preliminary data call for action, especially because BiH is a lower-middleincome country without mandatory FA food fortification program. Further research on folate dietary intake and folate status in the target group, as well as possible predictors of the low prevalence of supplementation, is recommended.

Sisters Together: Lessons Learned from Implementing a Grocery Store Campaign in Michigan Communities at Risk for Neural Tube Defects.

Sisters Together intended to develop and disseminate folic acid (FA) educational materials through a point-of-purchase program in low-income predominantly African American communities in Southeastern Michigan counties with high prevalence of neural tube defects (NTDs). Guided by the Theory of Reasoned Action and the Consumer Information Processing Model, 17 supermarkets hosted displays, shelf-signs, and food tastings and tracked purchases of FA sources, alongside customer-intercept and store manager surveys, and observational logs. Stocking and signage were implemented with moderate-to-high fidelity, and food tastings with high reach and dose. Purchases of black beans, spinach, orange juice, and supplements showed increases, although only a third of the women identified them as sources of FA. Only 21/122 women (17%) surveyed reported seeing the shelf-signs. Theory-driven, grocery store-centric interventions are effective strategies to address gaps in FA education, with the key behavior change mechanism appearing to be modeling "procedural knowledge."

Risk factors, presentation and outcome of meningomyelocele repair.

Objective:To determine the risk factors, presentation and outcome of meningomyelocele repairMethods:We reviewed 150 cases operated for meningomyelocele (MMC) at Jinnah Postgraduate Medical Centre Karachi between May 2015 and May 2018. Data of infants operated for MMC repair was extracted including socioeconomic status, maternal folate intake during pregnancy, head circumference, location and width of the defect, accompanying bladder and limb anomalies and treatments administered. Patients were followed up for a mean period of six months.Results:A total of 150 children were evaluated, out of which there were 83(55.3%) males and 67(44.7%) females. All belonged to low socio economic group and prenatal maternal folate intake as risk factor was positive in 103(68.7%) cases. Mean head circumference was 37.4 cm (range, 30.7 to 50 cm). Based on their location, 83(55%) of the defects were lumbosacral, 38(25.4%) were lumbar, 16(10.7%) were thoraco lumbar, 10(6.7%) were thoracic and three (2%) were cervical. Mean size of the meningomyelocele sac was 4.3 cm×5.6 cm (range, 1cm×2 cm to 11cm×8.4cm) and 21(14%) of the babies had a skin defect requiring flap. According to accompanying anomalies, 98(65.3%) of the babies had hydrocephalus, 13(9%) had club foot, four (2.7%) had diastematomyelia and three (2%) had tethered cord. Eighty seven (58%) patients had neurological deficit pre operatively and eight (5.4%) patients with normal power deteriorated after surgery out of which five (3.3%) developed paraplegia and three (2%) developed paraparesis. CSF leak was the major complication encountered in 16(11%) followed by meningitis in seven (5%), while the overall mortality was four (2.6%).Conclusion:The practice of periconceptional folic acid supplementation is essential to reduce the prevalence of neural tube defects (NTDs) in the developing world. Improved maternal nutrition with access to quality antenatal care is vital to decrease the prevalence and health burden.

Relationship of obesity with B vitamin status: analysis of NDNS data from UK women of reproductive age

AbstractPre-pregnancy obesity is associated with a 2-fold increased risk of Neural Tube Defects (NTD), an effect not explained by lower dietary folate intake, or non-use of folic acid supplements (as recommended globally to women before and in early pregnancy for NTD prevention). While the exact mechanism linking NTD and obesity is poorly understood, it is possible that a compromised status or metabolism of folate and/or of the closely related micronutrients (vitamin B12, B6 and riboflavin) may be involved. To date however, this hypothesis has not been adequately explored. This study therefore aimed to investigate the relationship of obesity with folate and related B vitamin biomarkers in a representative cohort of non-pregnant UK women of reproductive age. Data were accessed from the most recent UK National Diet and Nutrition Survey (NDNS; Years 7–8; 2015–16), a rolling cross-sectional survey designed to gather information from a representative sample of the UK population on nutrient intakes, food consumption and nutritional status. Data for women aged 16–45 years (non B vitamin supplement users; n 364), were extracted on: anthropometry (height, weight, body mass index [BMI] and waist circumference [WC]), dietary intakes of B vitamins and biomarkers for serum and red blood cell folate, vitamin B12 (total serum B12 and holotranscobalamin), vitamin B6 (plasma pyridoxal-5-phosphate [PLP]) and riboflavin (erythrocyte glutathione reductase activation coefficient EGRAac]). Prevalence of overweight and obesity (i.e. BMI: 25–30kg/m2 and &gt; 30kg/m2) was 28% and 22% respectively, whilst abdominal obesity (i.e. WC &gt; 88cm) was present in 31% of the women. Total serum B12 (r -0.215, P 0.012) and PLP (r -0.270, P 0.002) were negatively correlated with WC, with similar, albeit weaker, correlations found for BMI. Correspondingly, women with abdominal obesity compared to those without, had a lower status of total serum B12 (Median values of: 212 v 249 v pmol/L; P 0.049), B6 (31.5 v 40.5 nmol/L; P 0.002) and EGRac (1.43 v 1.36; P 0.031). No differences in B vitamin dietary intake were observed by categories of abdominal obesity. Abdominal obesity may be a risk factor for low status of both vitamins B12 and B6, independently of dietary intake. Further investigation to elucidate the potential underlying mechanism is warranted. These findings also highlight the importance of taking abdominal obesity into account, in addition to BMI, when examining possible adverse impacts of obesity on micronutrient status.

Urgent need for folic acid fortification of flour and grains: response to the 2019 UK Government’s public consultation

In June 2019, the UK Government took a step forward towards making a decision on the mandatory fortification of flour with folic acid (vitamin B9) in the prevention of neural...

84 Folate-methionine cycle and folate transport in developing buffalo embryos

Periconceptional folic acid is known to have a major role in the prevention of neural tube defects, leading to global recommendations for folic acid supplementation before and in early pregnancy. Maternal folate throughout pregnancy may have other roles in offspring health, including neurodevelopment and cognitive performance in childhood. Folate and folic acid (vitamin B9) act as a co-enzyme essential for single carbon metabolism, a network of pathways involved in several biological processes including nucleotide synthesis, DNA repair, and methylation reactions. In general, rapidly growing and multiplying cells require an adequate supply of folate. A primary deficiency of natural folate resulting in an increase of the total homocysteine concentration may be detrimental to the quality of the oocyte, subsequent fertilisation, embryogenesis, implantation, and fetal development. However, to date, folate-methionine metabolism and folate transport have not been studied in developing buffalo embryos. The present study details transcript expression for genes encoding key enzymes in the linked folate-methionine cycles in the ovary tissue, cumulus cells, immature oocytes, IVM oocytes, and pre-implantation embryos and also estimates the folate concentration in follicular fluid (FF) of buffalo. The FF was pooled and collected by aspiration of different sizes of surface follicles (2-8mm diameter). The total number of analysed samples was three, with different dilutions and estimation of folate in FF of buffalo done by chemiluminescence assay. Total RNA was extracted from oocytes, cumulus cells, ovarian tissue, and embryos produced from IVF. RT-PCR was performed to analyse the expression of folate-methionine cycle enzymes and folate transporters. Transcripts for all the enzymes of the folate-methionine cycle (i.e. SHMT, MTR, MTRR, MAT1A, MAT2B, GNMT, AHCY, CBS, and DHFR) and folate transporters (FOLR1, FOLR2) and reduced folate carrier (SLC19A1) were expressed in ovarian tissue, cumulus cells, oocytes, and pre-implantation embryos. Immunocytochemical analysis revealed FOLR2 and SLC19A1 protein expression on the plasma membrane and/or cytoplasm of the oocytes and embryos, and FOLR1 in the nucleus of pre-implantation embryos. The folate concentration in FF was 24ngmL−1. This is the first report to examine the concentration of folate in FF and revealed the identification of transcripts in different samples of buffalo species. The presence of these enzymes could have a profound effect on single-carbon metabolism within the ovary and pre-implantation embryo, therefore indicating that folate from FF is being disseminated through folate receptors within oocytes and embryos to participate in the folate pathway. This study advocates the necessity for examination of the result of folate supplementation throughout invitro embryo production for improving the quality and quantity of transferable blastocysts and subsequently live calf births in buffalo.

Erratum：葉酸サプリメントによる神経管閉鎖障害の予防：管理栄養士の認知率

Erratum：葉酸サプリメントによる神経管閉鎖障害の予防：管理栄養士の認知率

Vitamin B6 deficiency in new born rats affects hepatic cardiolipin composition and oxidative phosphorylation.

Vitamin B6 deficiency during pregnancy translates into a severe vitamin B6 deficiency (plasma levels decreased by 97%) in new-born rats. Further, hallmarks are increased (+89%) concentrations of homocysteine, gross changes in gene methylation and expression, and metabolic alterations including lipid metabolism. This study focuses on determining the effects of vitamin B6-deficiency on cardiolipin composition and oxidative phosphorylation in liver. For this purpose, hepatic cardiolipin composition was analyzed by means of LC/MS/MS, and mitochondrial oxygen consumption was determined by using a Clark-type electrode in a rat model of vitamin B6 deficiency. Liver mitochondria from new-born rats with pre-term vitamin B6 deficiency responded with substantial alterations in cardiolipin composition that include the following changes in the amounts of cardiolipin incorporated fatty acids: increase in C16, decrease in C18, decrease in saturated fatty acid, as well as increase in amount of oxidized cardiolipin species. These changes were accompanied by significantly decreased capacity of oxidative phosphorylation. In conclusion, vitamin B6 deficiency in new born rats induces massive alterations of cardiolipin composition and function of liver mitochondria. These findings support the importance of sufficient periconceptional supply of vitamin B6 to prevent vitamin B6 deficiency.Impact statementVitamin B6 (VitB6) is an active co-enzyme for more than 150 enzymes and is required for a great diversity of biosynthesis and metabolic reactions. There is an increased need for VitB6 during pregnancy and sufficient supply of VitB6 is crucial for the prevention of cleft palate and neural tube defects. We show that liver mitochondria from new-born rats with pre-term VitB6 deficiency respond with substantial alterations in cardiolipin (CL) composition and in the amount of oxidized CL species. These changes are associated with a decrease in the efficiency of oxidative phosphorylation. The results of this study support the significance of sufficient supply of VitB6 during pregnancy (and periconceptional) for diminishing the number of early abortions and minimizing malformation. The established link between VitB6 deficiency, CL composition, and mitochondrial respiration/energy production provides mechanistic insight as to how the VitB6 deficiency translates into the known pathophysiological and clinically relevant conditions.

Pre-conceptional folic acid supplementation: A possible cause for the increasing rates of ankyloglossia

BackgroundThere is an increasing awareness to ankyloglossia (tongue-tie) in infants, with marked increase in its report in the medical literature. Some reports indicate increase in prevalence. Whether the increase ankyloglossia rate is a real phenomenon or merely reflects increased awareness and reports has to be determined. One explanation for the increasing ankyloglossia rates is the growing trend of breast feeding initiation, often impaired by ankyloglossia, which brings it to medical attention. We propose an alternative hypothetical explanation based on increasing utilization of periconceptional folic acid supplementation for the prevention of neural tube defects (NTDs). Inadequate folic acid supply during organogenesis impairs cell division, and the mid-line structures are at the highest risk. We postulated that higher folic acid supply during organogenesis might enhance tissue synthesis with tighter closure of mid-line structures including the lingual frenulum, resulting in ankyloglossia. MethodsTo assess this hypothesis, we undertook an observational case control study comparing folic acid utilization before pregnancy in mothers of infants with and without ankyloglossia. Infants with ankyloglossia (n = 85) were compared to a control group without ankyloglossia (n = 140). ResultsThere was a slight, insignificant elevated frequency of reported utilization of folic acid (“any intake”) among mothers of infants with ankyloglossia compared with controls (74.1% and 66.4%, respectively). This difference was slightly higher, yet insignificant when folic acid intake “in most days” was considered (65.9% and 53.6%, respectively, OR = 1.67, 95%CI = 0.93–3.05, P = 0.07). In contrast, the reported intake of pre-conceptional folic acid “on a regular basis” was significantly higher among mothers of infants with ankyloglossia compared with controls (54.1% and 25.7%, respectively, OR = 3.41, 95%CI = 1.85–6.27, p < 0.0001). InterpretationThe reported association between higher frequency of regular pre-conceptional folic acid intake and ankyloglossia, supports the hypothesis for this association. More studies are required to test this hypothesis.

Modelling the impact of mandatory folic acid fortification of bread or flour in Ireland on the risk of occurrence of NTD-affected pregnancies in women of childbearing age and on risk of masking vitamin B12 deficiency in older adults

The rate of neural tube defects (NTDs) in Europe has remained similar since the 1990s despite folic acid supplement recommendations (400µg/day) for women of childbearing age. Mandatory folic acid fortification of staple foods has proved effective for reducing the prevalence of NTDs in over 80 countries. This study estimated the impact of addition of folic acid to bread or flour in the Republic of Ireland on reducing the risk of occurrence of NTD-affected pregnancies and the possible risk of masking (undiagnosed) vitamin B12 deficiency in older adults. Analyses were based on the Irish National Adult Nutrition Survey (2008-2010). Folic acid fortification was modelled using DaDiet© software. Estimates were made of the increase in average daily folic acid intake in women (18-50years) and the risk of exceeding the tolerable upper intake level (UL) of 1000µg for folic acid in adults over 50years of age. The fortification scenarios examined would reduce the risk of NTD-affected pregnancies by 8-32%, corresponding to an increase of 39-152μg in the mean daily folic acid intake of WCBA. The risk of masking anaemia associated with vitamin B12 deficiency in older adults would be negligible as the probability of exceeding the UL for folic acid, even by a small amount, is very low (≤ 0.2%). These levels of addition of folic acid to bread or flour would effectively reduce the risk of NTDs while allowing safe consumption of folic acid at current levels from other fortified foods and supplements.

Association of maternal folate status in the second trimester of pregnancy with the risk of gestational diabetes mellitus.

Interest in the high folate status of pregnant women has increased due to its role in the prevention of neural tube defects (NTDs). The effect of increased red blood cell (RBC) folate status during the second trimester of pregnancy on gestational diabetes mellitus (GDM) remains unclear. We measured RBC folate concentrations by competitive protein‐binding assay and obtained clinical information from electronic medical records. Logistic regression analysis was used to explore the associations of RBC folate concentrations with risks of gestational diabetes mellitus (GDM). We further assessed the potential nonlinear relations between continuous log‐transformed RBC folate concentrations and GDM risk by using the restricted cubic splines. We observed high RBC folate concentrations in GDM patients compared to control group [median (interquartile range, IQR), GDM vs. controls: 1,554.03 (1,240.54–1,949.99) vs. 1,478.83 (1,124.60–1,865.71) nmol/L, p = .001]. Notably, high folate concentrations were significantly associated with an increased risk of GDM [RR per 1‐SD increase: 1.16 (1.03, 1.30), p = .012] after adjustment for maternal age, parity, and body mass index (BMI) at enrollment. In the restricted cubic spline model, a test of the null hypothesis of the linear relationship was rejected (p = .001). Our study firstly showed that maternal RBC folate concentrations during the second trimester of pregnancy increase the risk of GDM in a Chinese population. Further randomized clinical trials (RCTs) are warranted to confirm the adverse effect.

Associations between Cumulative Environmental Quality and Neural Tube Defects

TPS 741: Adverse birth outcomes 2, Exhibition Hall, Ground floor, August 28, 2019, 3:00 PM - 4:30 PM Background/Aims: Neural tube defects (NTD), including anencephaly, spina bifida (SB), and encephalocele, are some of the most severe birth defects. The impact of how cumulative environmental quality contributes to associations with NTDs is unknown. The Environmental Quality Index (EQI) is a comprehensive measure of cumulative environmental exposures for five domains (air, water, land, sociodemographic, built) from 2000-2005. Methods: We conducted a county-level analysis to assess the associations between the EQI and four birth defects (NTD, anencephaly, SB, and encephalocele) using data from the Texas Birth Defects Registry and live birth records from 2000-2006. Prevalence ratios (PR) and 95% confidence intervals (CI) were estimated from Poisson regression models between the NTD defects and the EQI, represented by three exposure categories based on percentiles (<50%, or “better” environmental quality; 50-75%, “mid”; >75%, “worst”), adjusted for potential confounders. Results: We observed non-linear trends for overall EQI and the water domain, with increased prevalence of birth defects observed in the mid versus better environmental quality categories. For overall EQI, mid environmental quality was associated with higher prevalence of NTDs [PR=1.27, 95%CI: 1.06, 1.52], anencephaly [1.39 (1.16, 1.66)], SB [1.18 (0.98, 1.42)], and encephalocele [1.34 (1.11, 1.60)], as compared to better environmental quality. In the water domain, mid environmental quality was associated with higher prevalence of each of these four outcomes [NTDs: 1.58 (1.14, 1.78); anencephaly: 2.29 (2.03, 2.57); SB: 1.46 (1.30, 1.65); encephalocele 1.01 (0.90, 1.13)]. Comparing worst environmental quality to better environmental quality for the sociodemographic domain, the PRs were 2.14 (1.93, 2.37) for NTDs, 3.32 (3.00, 3.68) for anencephaly, 1.91 (1.72, 2.12) for SB, and 1.12 (1.00, 1.25) for encephalocele. In the air, land, and built domains, inverse associations were observed with all birth defects studies. Conclusions: We found that sociodemographic factors, water quality, and overall environmental quality contribute to associations with these NTD outcomes, but not with air, land or built environmental quality. This abstract does not reflect EPA policy.

Impact of gestational hypertension and preeclampsia on fetal gender: A large prospective cohort study in China.

Recent studies suggested an association between fetal sex preponderance and hypertensive disorders during pregnancy, but the conclusions were inconsistent. Our objective was to investigate whether the occurrence of gestational hypertensive disorders would affect the possibility of delivering boys. Data were obtained from the China-US Collaborative Project for Neural Tube Defects Prevention, a large population-based cohort study. We included participants who were registered in 2 southern Chinese provinces, and whose information of blood pressure and sex delivery were recorded in detailed. Blood pressure was measured during pregnancy by trained health care workers and other health-related information was recorded prospectively. We used log-binomial regression to evaluate the association between gestational hypertension or preeclampsia and the chance of male delivery. Among 205,605 singleton pregnancy women, the overall incidences of gestational hypertension and preeclampsia were 9.5% and 2.4%, respectively. The prevalence of male delivery was 51.1% and 50.2% in the groups of gestational hypertension and preeclampsia, while in the normotension group was 52.0%. After adjustment for the effects of the main potential confounders, women with gestational hypertension and preeclampsia both showed significantly decreased probability of giving birth to a boy. The adjusted risk ratios (RRs) were 0.98 (95% confidence interval (CI): 0.97-0.99) and 0.96 (95% CI: 0.94-0.99), respectively. Our results support a slight but significant association between gestational hypertension or preeclampsia and decreased likelihood of male delivery.

Folic Acid for the Prevention of Fetal Neural Tube Defects

The use of folic acid supplements before and during the first three months of pregnancy significantly reduces the risk of fetal neural tube defects (NTDs). This study assessed knowledge and factors that influence the use of folic acid, the actual use of folic acid and its relationship with socio-demographic factors among women of childbearing age in the Ife Central Local Government, Ile-Ife, Osun State, Nigeria. A cross-sectional descriptive design was adopted to select 400 women of childbearing age who participated in the study using a self-structured questionnaire. Results from this study showed that 39.8 per cent of the study participants had good knowledge about the benefits of folic acid, 64.6 per cent of the participants reported to have used folic acid at one time in their lives, while 55.5 per cent of them reported not to have taken folic acid before their pregnancy. This study also revealed a significant association between the respondents’ socio-demographic factors and the use of folic acid with a p-value of .000 (p-value &lt; 0.05). The study concluded that knowledge about the use of folic acid for the prevention of NTDs among women of childbearing age is not adequate and that very few of them used folic acid at the appropriate time.

Congenital anomalies and associated risk factors in a Saudi population: a cohort study from pregnancy to age 2 years

ObjectiveTo assess the three key issues for congenital anomalies (CAs) prevention and care, namely, CA prevalence, risk factor prevalence and survival, in a longitudinal cohort in Riyadh, Saudi Arabia.SettingTertiary care...

Defining the plasma folate concentration for optimal neural tube defects prevention cannot ignore the impact of the employed methodology

Defining the plasma folate concentration for optimal neural tube defects prevention cannot ignore the impact of the employed methodology

Lack of historical evidence to support folic acid exacerbation of the neuropathy caused by vitamin B12 deficiency

In 1998 a Tolerable Upper Intake Level (UL) for folic acid was established based on case reports from the 1940s suggesting that high-dosage folic acid intake, used to treat patients with pernicious anemia, had the potential to precipitate or speed-up the development of neurological problems. This UL has been employed in the decision-making process used by more than 80 countries to establish programs to fortify staple foods with folic acid to prevent neural tube birth defects. Some have claimed that this UL is flawed and has become an obstacle to the wider adoption of neural tube defect prevention programs and have called for re-evaluation of the scientific validity of this UL. Case reports cannot establish causality, but they can reveal patterns in the timing of the onset and treatment of patients with pernicious anemia. These patterns can be compared with secular trends of usual medical practice for the treatment of pernicious anemia and with the changes in usage of folic acid preparations, including recommended therapeutic dosage and precautions for its usage surrounding the synthesis of folic acid in 1945 and vitamin B12 in 1948. Folic acid package inserts, early editions of hematology textbooks, and international expert reports provide valuable historical information. The recommended therapeutic daily dosage for folic acid of 5-20 mg was unchanged from 1946 through to 1971. The likely cause of the neurological problems encountered is the development of vitamin B12 neuropathy when pernicious anemia was treated with high-dosage folic acid before vitamin B12 was widely available in the early 1950s. Thus, the historical record does not provide compelling evidence that folic acid can potentially cause neurologic complications among those with low vitamin B12 status and lends support for reconsidering the basis for the UL of folic acid.

Neural-Tube Defects and Antiretroviral Treatment Regimens in Botswana

BackgroundA preliminary safety signal for neural-tube defects was previously reported in association with dolutegravir exposure from the time of conception, which has affected choices of antiretroviral treatment (ART) for human immunodeficiency virus (HIV)–infected women of reproductive potential. The signal can now be evaluated with data from follow-up of additional pregnancies.MethodsWe conducted birth-outcomes surveillance at hospitals throughout Botswana, expanding from 8 to 18 sites in 2018. Trained midwives performed surface examinations of all live-born and stillborn infants. Research assistants photographed abnormalities after maternal consent was obtained. The prevalence of neural-tube defects and major external structural defects according to maternal HIV infection and ART exposure status was determined. In the primary analyses, we used the Newcombe method to evaluate differences in prevalence with 95% confidence intervals.ResultsFrom August 2014 through March 2019, surveillance captured 119,477 deliveries; 119,033 (99.6%) had an infant surface examination that could be evaluated, and 98 neural-tube defects were identified (0.08% of deliveries). Among 1683 deliveries in which the mother was taking dolutegravir at conception, 5 neural-tube defects were found (0.30% of deliveries); the defects included two instances of myelomeningocele, one of anencephaly, one of encephalocele, and one of iniencephaly. In comparison, 15 neural-tube defects were found among 14,792 deliveries (0.10%) in which the mother was taking any non-dolutegravir ART at conception, 3 among 7959 (0.04%) in which the mother was taking efavirenz at conception, 1 among 3840 (0.03%) in which the mother started dolutegravir treatment during pregnancy, and 70 among 89,372 (0.08%) in HIV-uninfected mothers. The prevalence of neural-tube defects was higher in association with dolutegravir treatment at conception than with non-dolutegravir ART at conception (difference, 0.20 percentage points; 95% confidence interval [CI], 0.01 to 0.59) or with other types of ART exposure. Major external structural defects were found in 0.95% of deliveries among women exposed to dolutegravir at conception and 0.68% of those among women exposed to non-dolutegravir ART at conception (difference, 0.27 percentage points; 95% CI, −0.13 to 0.87).ConclusionsThe prevalence of neural-tube defects was slightly higher in association with dolutegravir exposure at conception than with other types of ART exposure at conception (3 per 1000 deliveries vs. 1 per 1000 deliveries). (Funded by the National Institutes of Health.)

The search for genetic determinants of human neural tube defects.

An update is presented regarding neural tube defects (NTDs) including spina bifida and anencephaly, which are among the most common serious birth defects world-wide. Decades of research suggest that no single factor is responsible for neurulation failure, but rather NTDs arise from a complex interplay of disrupted gene regulatory networks, environmental influences and epigenetic regulation. A comprehensive understanding of these dynamics is critical to advance NTD research and prevention. Next-generation sequencing has ushered in a new era of genomic insight toward NTD pathophysiology, implicating novel gene associations with human NTD risk. Ongoing research is moving from a candidate gene approach toward genome-wide, systems-based investigations that are starting to uncover genetic and epigenetic complexities that underlie NTD manifestation. Neural tube closure is critical for the formation of the human brain and spinal cord. Broader, more all-inclusive perspectives are emerging to identify the genetic determinants of human NTDs.

Choline, not folate, can attenuate the teratogenic effects ofdibutyl phthalate (DBP) during early chick embryo development.

Dibutyl phthalate (DBP), a persistent environmental pollutant, can induce neural tube abnormal development in animals. The possible effects of DBP exposure on human neural tube defects (NTDs) remain elusive. In this study, the distribution of DBP in the body fluid of human NTDs was detected by GC-MS. Then, chick embryos were used to investigate the effects of DBP on early embryonic development. Oxidative stress indicators in chick embryos and the body fluid of human NTDs were detected by ELISA. The cell apoptosis and total reactive oxygen species (ROS) level in chick embryos were detected by whole-mount TUNEL and oxidized DCFDA, respectively. The study found that the detection ratio of positive DBP and its metabolites in maternal urine was higher in the NTD population than that in normal controls. 8-hydroxy-2 deoxyguanosine (8-OHDG) and malondialdehyde (MDA) were evidently upregulated and superoxide dismutase (SOD) was observably downregulated in amniotic fluid and urine. Animal experiments indicated that DBP treatment induced developmental toxicity in chick embryos by enhancing the levels of oxidative stress and cell apoptosis. MDA was increased and SOD was decreased in DBP-treated embryos. Interestingly, the supplement of high-dose choline (100 μg/μL), not folic acid, could partially restore the teratogenic effects of DBP. Our data collectively suggest that the incidence of NTDs is closely associated with DBP exposure. This study may provide new insight for NTD prevention.