Folic Acid Supplementation Research Articles

Neural Tube Defect in a Resource Limited Setting: Clinical Profile and Short Term Outcome.

There is a huge burden of neural tube defect (NTD) in Ethiopia, and surgical management is not readily available. We aimed to assess the clinical profile and hospital outcome of children with NTD that were operated in Hawassa University Comprehensive Specialized Hospital, Hawassa, Ethiopia. A retrospective cross-sectional study on 250 children with NTD that were treated in a tertiary hospital from March 2016 to May 2020 was conducted to describe the clinical profile and treatment outcome at discharge. Logistic regression analysis was carried out to evaluate factors that determine mortality. Out of the 250 children, 50.4% were male. Myelomeningocele was the most common type of NTD (77.2%) followed by meningocele (10.4%). Only 3 mothers (1.2%) received periconceptional folic acid. Prenatal diagnosis of NTD was made in only 22 (8.8%) cases. 52.8% of the NTDs were ruptured at presentation and 50.8% had associated sepsis. At presentation, 42.4% were ≤72 hours of age and only 18 neonates (7.2%) were operated within 72 hours of admission. 54% had associated hydrocephalus, 31.6% had Chiari II malformation and 19.6% had club foot. Surgical site infection, post MMC repair hydrocephalus, and meningitis were seen in 8%, 14% and 16.8% of the participants, respectively. The mean duration of hospitalization was 24 ± 14.4 days. Twenty patients (8%) died before discharge from hospital. Prematurity [AOR: 26 (95% CI: 8.01, 86.04), P < 0.001] and the presence of meningitis [AOR: 3.8 (95% CI: 1.12,12.9), P = 0.03]were determinants of mortality. NTDs are substantial health problem in this part of the country. Periconceptional folic acid supplementation is almost non-existent. Prenatal detection of NTDs is very low and management is delayed in the majority of cases. Myelomeningocele is the most common type of NTD. There is high in-hospital mortality, and prematurity and the presence of meningitis are its determinants.

Advanced Messaging Intervention for Medication Adherence and Clinical Outcomes Among Patients With Cancer: Randomized Controlled Trial.

Medication adherence is crucial for improving clinical outcomes in the treatment of patients with cancer. The lack of adherence and adverse drug reactions can reduce the effectiveness of cancer therapy including the quality of life. The commonly used intervention methods for medication adherence continue to evolve, and the age of fifth-generation (5G) messaging has arrived. In this study, we conducted a prospective, pilot randomized controlled trial to evaluate the effect of 5G messaging on medication adherence and clinical outcomes among patients with cancer in China. The research population was patients with nonsmall cell lung cancer undergoing pemetrexed chemotherapy who require regular folic acid (FA) and vitamin B12 supplements. The intervention and control groups were assigned to 5G messaging and second-generation (2G) messaging, respectively. The patients' medication adherence and quality of life were assessed at baseline and 1-month and 3-month time points. Moreover, the chemotherapy-related hematologic or nonhematologic toxicities, as well as the serum levels of FA and vitamin B12, were measured. Of the 567 patients assessed for eligibility between January and May 2021, a total of 154 (27.2%) patients were included. Overall, 80 were randomized to the control group and 74 to the intervention group. The odds of adherence in the 5G messaging intervention group were significantly higher than the control group at the 1-month (62/69, 90% vs 56/74, 76%; adjusted odds ratio 2.67, 95% CI 1.02-7.71) and 3-month (50/60, 83% vs 48/64, 75%; adjusted odds ratio 2.36, 95% CI 1.00-5.23) time points. Correspondingly, the FA and vitamin B12 serum levels of patients in the 5G messaging group were higher than those of the control group. Regarding hematologic toxicities, only the incidence of leukopenia in the intervention group was lower than that in the control group (25/80, 31% in the control group vs 12/74, 16% in the intervention group; P=.04). There were no differences in nonhematologic toxicities and quality of life between the 2 groups. In summary, we conclude that compared with conventional 2G text-based messaging, a 5G messaging intervention can better improve medication adherence and clinical outcome among patients with cancer. Chinese Clinical Trial Registry ChiCTR2200058188; https://www.chictr.org.cn/showproj.html?proj=164489.

The Effect of Vitamin D, B12, and Folic Acid Supplements in Relieving Major Depressive Symptoms, General Anxiety Disorder among Adults and Adolescents - A Systemic Article Review

Depression and anxiety disordersare a heterogeneous disorders and are thought to develop as a result of complex interactions between genetic and environmental Factors.(1) Vitamin D deficiency is the most common cause of Osteomalacia among adults and adolescents with its associated classical symptoms such as bones pain, muscle weakness which may affect productivity, daily activates, school and work absence and mood. Vitamin B12 deficiency causes complex hematological and neurological signs and symptoms as easy fatigability, lethargy, pallor, ictrous, paresthesia, difficulty of balance or loss of proprioception and neuropsychiatric symptoms may be presented in severe cases. Vitamin B9 deficiency is a rare condition causes complex hematological signs and symptoms as easy fatigability, lethargy, pallor, ictrous, symptoms may be presented in severe cases. Aim of the study: To review articles studying the relationship between Vitamin D deficiency and/ or vitamin B12 deficiency, and/or B9 deficiency levels and supplements in relieving major depression (MDD) and general anxiety disorder (GAD) symptoms.

Hyperhomocysteinaemia Promotes Doxorubicin-Induced Cardiotoxicity in Mice.

Doxorubicin, a widely used chemotherapeutic drug in clinical oncology, causes a series of cardiac side effects referred to as doxorubicin-induced cardiotoxicity. Hyperhomocysteinaemia is an independent risk factor for multiple cardiovascular diseases. However, whether hyperhomocysteinaemia contributes to doxorubicin-induced cardiotoxicity is currently unknown. In this study, we explored the pathogenic effects of hyperhomocysteinaemia induced by dietary methionine supplementation (2% wt/wt in rodent chow) in a mouse model of doxorubicin-induced cardiotoxicity. Our data showed that methionine supplementation doubled serum homocysteine levels, inducing mild hyperhomocysteinaemia. Doxorubicin at a cumulative dosage of 25 mg/kg body weight led to significant weight loss and severe cardiac dysfunction, which were further exacerbated by methionine-induced mild hyperhomocysteinaemia. Doxorubicin-induced cardiac atrophy, cytoplasmic vacuolisation, myofibrillar disarray and loss, as well as cardiac fibrosis, were also exacerbated by methionine-induced mild hyperhomocysteinaemia. Additional folic acid supplementation (0.006% wt/wt) prevented methionine-induced hyperhomocysteinaemia and inhibited hyperhomocysteinaemia-aggravated cardiac dysfunction and cardiomyopathy. In particular, hyperhomocysteinaemia increased both serum and cardiac oxidative stress, which could all be inhibited by folic acid supplementation. Therefore, we demonstrated for the first time that hyperhomocysteinaemia could exacerbate doxorubicin-induced cardiotoxicity in mice, and the pathogenic effects of hyperhomocysteinaemia might at least partially correlate with increased oxidative stress and could be prevented by folic acid supplementation. Our study provides preliminary experimental evidence for the assessment of hyperhomocysteinaemia as a potential risk factor for chemotherapy-induced cardiotoxicity in cancer patients.

Genome-wide interaction analysis of folate for colorectal cancer risk

BackgroundEpidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate’s role in CRC. ObjectivesOur aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. MethodsWe applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). ResultsInverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. ConclusionsVariation in 3p25.2 locus may modify the association of folate supplement with CRC risk. Experimental studies and studies incorporating other relevant omics data are warranted to validate this finding.

Impact of Homocysteine as a Preconceptional Screening Factor for In Vitro Fertilization and Prevention of Miscarriage with Folic Acid Supplementation Following Frozen-Thawed Embryo Transfer: A Hospital-Based Retrospective Cohort Study.

Homocysteine is an amino acid naturally produced in the body and metabolized via the methionine cycle. High homocysteine levels can increase the risk of infertility and pregnancy complications, such as preeclampsia, preterm delivery, miscarriage, and low birth weight. Preconceptional homocysteine levels may be reduced by taking folic acid supplements to reduce the risk of such complications. This cross-sectional, hospital-based study was conducted to examine the role of homocysteine in 1060 infertile women with a history of IVF/intracytoplasmic sperm injection (ICSI) failure. We analyzed whether folic acid intervention altered homocysteine levels and influenced reproductive outcome. We found that a higher homocysteine level was statistically associated with a lower fertilization rate in patients with a history of IVF/ICSI failure. There was an inverse relationship between homocysteine levels and serum 25(OH)VD, and a trend towards lower anti mullerian hormone in the group with higher homocysteine levels. This is the first interventional study to identify that folic acid supplementation improved pregnancy outcomes following freeze embryo transfer (FET) in women with a history of FET failure by monitoring the reduction in homocysteine levels. Therefore, folic acid supplementation and homocysteine level monitoring may constitute a novel intervention for improving IVF/ICSI pregnancy outcomes.

Complementary and alternative medicine use by pregnant women in Japan: a pilot survey

BackgroundComplementary and alternative medicine (CAM) are popular among women, and are used during their pregnancy in Japan. This study aimed to survey the prevalence of CAM use by healthy pregnant women as a health-care prescribed therapy or self-care and to investigate the factors associated with CAM use in Japan.MethodsIn this cross-sectional study, pregnant women after 34 weeks of gestation were asked to respond to a questionnaire at the clinic or online. The questionnaire comprised questions on the participants’ characteristics and their use of CAM for therapy and self-care. Descriptive statistics were calculated in the analyses, and bivariate and multivariate logistic analyses were performed to evaluate the associations between factors and CAM use.ResultsA total of 394 women responded from three hospitals, two clinics, and two midwifery birth centers. CAM was received as treatment by practitioners during pregnancy by 75 women (19.0%). The following therapies were used: traditional Chinese medicine (7.9%), chiropractic (6.9%), moxibustion (6.4%), and acupuncture (5.3%). One or more types of therapy were used as self-care by 348 women (88.3%). Highly used CAM for self-care were: folic acid supplementation (75.4%), other supplements (51.5%), herbs (20.8%), and yoga (19.0%). Multiple logistic regression analyses revealed that the factors associated with CAM use as a therapy were midwifery birth centers for planned childbirth settings (adjusted odds ratio [AOR] 3.64, 95% confidence interval [CI] [1.69–7.83]) and pregnancy complications diagnosed (AOR 2.46, 95%CI [1.38–4.39]). The factors associated with CAM use for self-care were age 30–39 years (AOR 4.48, 95%CI [2.14–9.73]) and over 40 years (AOR 3.92, 95%CI [1.10–13.91]), junior college education or above (AOR 2.30, 95%CI [1.18–4.51]), and primiparas (AOR 3.82, 95%CI [1.86–7.86]). The most common source of information was the “Internet” (43.8%).ConclusionsApproximately 20% of Japanese pregnant women received CAM as therapy by practitioners, and the related factors were: tended to have baby at midwifery birth center and pregnancy complications. Almost 90% of respondents used CAM as self-care and the related factors were: older, had a higher educational level and tended to be primiparas. They used the Internet as their main source of information about CAM. Health care providers need to provide evidenced-based information on CAM and to help decision making to ensure safe and effective CAM utilization by pregnant women.

Quality of Antenatal Care Services in Four Accredited Primary Health Care Centers in Cairo, Egypt

Abstract Background Antenatal care (ANC) is a careful, systematic assessment and follow-up of pregnant women, that includes education, counseling, screening, and treatment to assure the best possible health of the mother and her fetus. In order to assure each women gets the best quality of care, quality assessment of all items of antenatal care should be arranged regularly. This study aims to measure the perceived quality of antenatal care services, the adherence of the primary care physician to the Egyptian ministry of health guidelines as well as the overall satisfaction of pregnant women about their antenatal care services. Methods A cross sectional study was conducted from January till April 2021 among women aged 1849 years old who attend antenatal care clinics at four primary health centres in Cairo, Egypt. All health centres included in the study are government run facilities. Results Despite the high overall satisfaction (98%) reported for the antenatal care services, the total quality score was low (&amp;lt;60%), the highest satisfaction was reported from most of accessibility point and cleanliness of the primary care centers, answering inquiries, number of the doctors, discussion of the delivery plan, health education about importance of folic acid and iron supplements, family planning and cost of the service. Lowest satisfaction reported from the PHC was for working hours of the center, history taking, examination time, health education about diet, breastfeeding, and the harmful effects of passive smoking. Although most women reported that they had the majority of the Egyptian antenatal guidelines covered by their physician, items like past medical history, personal hygiene and oral glucose challenge test were missed. Conclusion The findings showed the need for new approaches to upgrade the quality of antenatal care and improve the health education skills for the primary care physicians, despite the high overall satisfaction.

Association of MTHFR polymorphism, folic acid and vitamin B12 with serum homocysteine levels in pregnant women.

Homocysteine is known to be associated with adverse vascular and metabolic effects, as well as pregnancy complications. Its serum levels are influenced by the function of the enzyme methylenetetrahydrofolate reductase (MTHFR) and the dietary intake of folic acid, vitamin B12, and methionine. In this cross-sectional study, we investigated the association of genetic polymorphisms of the MTHFR gene with vitamin status in pregnant women during mandatory folic acid supplementation. The study included 102 pregnant women between 24 and 28 weeks of gestation who were attending regular outpatient examinations at the maternity clinic. Homocysteine, folic acid, vitamin B12 levels, and MTHFR gene polymorphisms (C677T and A1298C) were analyzed. Significant associations were found between vitamin B12 and folic acid levels with homocysteine (P < 0.001), with lower serum levels of these vitamins being associated with higher homocysteine levels. Surprisingly, there was no significant association between MTHFR genetic polymorphisms and serum homocysteine levels, likely attributed to the supplementation of folic acid and vitamin B12 in vitamin supplements for pregnant women, which counteracts the effect of the mutation. Remarkably, a high prevalence of MTHFR gene mutations was found, with the C677T polymorphism present in 56.9% and the A1298C polymorphism in 87.2% of pregnant women. These findings emphasize the importance of adequate folic acid and vitamin B12 intake during pregnancy to regulate homocysteine levels. Although the MTHFR gene mutations were highly prevalent, their influence on homocysteine levels in this population appears to be mitigated by vitamin supplementation. Further research is warranted to explore the impact of these mutations on other aspects of pregnancy outcomes. The trial is registrated at Clinicaltrail.gov (NCT04952324).

Folic acid improved memory and learning function in a rat model of neuroinflammation induced by lipopolysaccharide.

Folic acid (FA) plays an important role in the maintenance of normal neurological functions such as memory and learning function. Neuroinflammation contributes to the progression of cognitive disorders and Alzheimer's disease. Thus, this study aimed to investigate the effect of FA supplementation on cognitive impairment, oxidative stress, and neuro-inflammation in lipopolysaccharide (LPS)-injured rats. For this purpose, the rats were given FA (5-20 mg/kg/day, oral) for 3weeks. In the third week, LPS (1 mg/kg/day; intraperitoneal injection) was given before the Morris water maze (MWM) and passive avoidance (PA) tests. Finally, the brains were removed for biochemical assessments. In the MWM test, LPS increased the escape latency and traveled distance to find the platform compared to the control group, whereas all doses of FA decreased them compared to the LPS group. The findings of the probe trial showed that FA increased the traveling time and distance in the target area. LPS impaired the performance of the rats in the PA test. FA increased delay and light time while decreasing the frequency of entry and time in the dark region of PA. LPS increased hippocampal levels of interleukin (IL)-6 and IL-1β. The hippocampal level of malondialdehyde was also increased but thiol content and superoxide dismutase activity were decreased in the LPS group. However, treatment with FA restored the oxidative stress markers along with a reduction in the levels of pro-inflammatory cytokines. In conclusion, FA could ameliorate the memory and learning deficits induced by LPS via normalizing the inflammatory response and oxidative stress markers in the brain.

Factors Associated with Neural Tube Defects among Women Who Gave Birth at Adama Hospital Medical College, Adama, Ethiopia: A Case Control Study.

Neural tube defects (NTDs) occur as a result of incomplete closure of the neural tube by the embryonic age of 26 to 28 days. Addressing factors associated with NTDs would help to identify and prioritize high-risk women, which in turn guides the preventive strategy. The study aimed to identify factors associated with NTDs among women who gave birth or had a second-trimester abortion at Adama Hospital Medical College, from January 1st to December 31st, 2019. Hospital based unmatched case-control study was conducted on 344 women. Data were analyzed with SPSS 20. Descriptive statistics were computed. Binary logistic regression analysis was performed to determine factors associations with NTDs. The odds of having a fetus with NTDs were 2.19 times higher among women who are not in a marital relationship (AOR = 2.19; 95% CI: 1.13, 4.25). Women with a previous history of Abortion or stillbirth had 3 fold increased risk of having a fetus with NTDs (AOR = 3.05; 95% CI: 1.58, 5.88). Inadequate housing condition nearly doubles the odds of having a fetus with NTDs (AOR = 1.91; 95% CI: 1.20, 3.04). Folic acid or multivitamin supplementation early in pregnancy reduced the odds of having a fetus with NTDs by 43% (AOR = 0.57; 95% CI: 0.35, 0.91). Being not in a marital relationship, previous history of abortion or stillbirth, and living in inadequate housing conditions were risk factors for NTDs, while multivitamins or folic acid supplementation was a protective factor.

Molecular regulatory mechanism of key LncRNAs in subclinical mastitic cows with folic acid supplementation

BackgroundFolic acid is a water-soluble B vitamin (B9), which is closely related to the body’s immune and other metabolic pathways. The folic acid synthesized by rumen microbes has been unable to meet the needs of high-yielding dairy cows. The incidence rate of subclinical mastitis in dairy herds worldwide ranged between 25%~65% with no obvious symptoms, but it significantly causes a decrease in lactation and milk quality. Therefore, this study aims at exploring the effects of folic acid supplementation on the expression profile of lncRNAs, exploring the molecular mechanism by which lncRNAs regulate immunity in subclinical mastitic dairy cows.ResultsThe analysis identified a total of 4384 lncRNA transcripts. Subsequently, differentially expressed lncRNAs in the comparison of two groups (SF vs. SC, HF vs. HC) were identified to be 84 and 55 respectively. Furthermore, the weighted gene co-expression network analysis (WGCNA) and the KEGG enrichment analysis result showed that folic acid supplementation affects inflammation and immune response-related pathways. The two groups have few pathways in common. One important lncRNA MSTRG.11108.1 and its target genes (ICAM1, CCL3, CCL4, etc.) were involved in immune-related pathways. Finally, through integrated analysis of lncRNAs with GWAS data and animal QTL database, we found that differential lncRNA and its target genes could be significantly enriched in SNPs and QTLs related to somatic cell count (SCC) and mastitis, such as MSTRG.11108.1 and its target gene ICAM1, CXCL3, GRO1.ConclusionsFor subclinical mastitic cows, folic acid supplementation can significantly affect the expression of immune-related pathway genes such as ICAM1 by regulating lncRNAs MSTRG.11108.1, thereby affecting related immune phenotypes. Our findings laid a ground foundation for theoretical and practical application for feeding folic acid supplementation in subclinical mastitic cows.

Prevalence of Anemia, Knowledge, Attitude and Compliance Related to Weekly Iron Folic Acid Supplementation Programme among the Adolescents in Selected School of South East Delhi

Prevalence of Anemia, Knowledge, Attitude and Compliance Related to Weekly Iron Folic Acid Supplementation Programme among the Adolescents in Selected School of South East Delhi

Folic acid supplementation improved cognitive deficits associated with lithium administration during pregnancy in rat offspring.

The present study aimed to analyse both neurobehavioural and biochemical results of neonates born of mothers exposed to different doses of lithium along with the groups that received lithium at the highest dose with folic acid as a preventive treatment. Male and female rats were mated in separate cages, and pregnant rats were divided into eight first group as (1) vehicle; (2) propylthiouracil (PTU)-induced hypothyroidism; (3-4) received two different doses of lithium carbonate (15 and 30 mg/kg); (5-7) the highest doses of lithium (30 mg/kg) plus three different doses of folic acid (5, 10 and 15 mg/kg); and (8) received just folic acid (15 mg/kg). All treatments were dissolved in drinking water and continued until delivery, followed by returning to a regular diet without treatment. Lithium (30 mg/kg) disrupts both behavioural and biochemical markers, including TSH, T3 and T4 as measuring indicators to assess thyroid function, IL-10 and TNF-α as anti-inflammatory and inflammatory agents, respectively, malondialdehyde as an oxidative stress marker, alongside SOD, and catalase activity as antioxidant indicators. Besides, folic acid, almost at the highest dose (15 mg/kg), attenuated memory impairement and anxiety-like behaviour caused by lithium. Moreover, the groups treated with folic acid alone in comparison with vehicles demonstrated higher levels of antioxidant and anti-inflammatory indicators. According to the results, prenatal exposure to a high dose of lithium (30 mg/kg) leads to foetal neurodevelopmental disorder and growth restriction through various mechanisms more likely attributed to hypothyroidism, which means it should be either prohibited or prescribed cautiously during pregnancy.

Management of anaemia in pregnancy using ‘test and treat’ strategy: hospital based open randomized study

In India, prevalence of nutritional anaemia due to iron, folic acid and vitamin B12 deficiency is high. National anaemia control programme envisaged detection and treatment of anaemic pregnant women. Prevalence of anaemia continues to be high because this strategy was not operationalised and coverage and compliance with iron folic acid supplementation remains low. : The present study aimed at: 1. Operationalizing Hb estimation in urban maternity center, 2. assessing prevalence of iron, folic acid and vitamin B12 deficiency, 3. undertaking an open randomized study in women with Hb between 8.0 and 10.9 g/dL to assess impact of supplementation with iron and folic acid (Group 1) or iron, folic acid and vitamin B 12 (Group 2). The ‘Test and treat’ strategy was operationalized in urban maternity center. At enrolment 100% of women were anaemic, 60% had ferritin &amp;#60;12ng/ml, 5% had folic acid &amp;#60;3ng/ml and 1/3 had vitamin B12 &amp;#60;200pg/ml. After eight weeks of supplementation, there was an increase in mean Hb (&amp;#62;1.0 g/dL), mean ferritin and folic acid in both Gr 1 and 2. There was a fall in mean vitamin B12 at 8 weeks in Gr 1 women who received 5 mg folic acid. Addition of vitamin B12 to IFA does not improve mean Hb or vitamin B12.With assured regular supply and supportive supervision, iron folic acid supplementation for 8 weeks reduces prevalence of anaemia in pregnancy by 50%; with continued supplementation till 38 weeks of pregnancy, there was 70% reduction in prevalence of anaemia.

Folate deficiency increases the incidence of dolutegravir-associated foetal defects in a mouse pregnancy model

Dolutegravir (DTG) is a recommended first-line regimen for all people with Human Immunodeficiency Virus (HIV) infection. Initial findings from Botswana, a country with no folate fortification program, showed an elevated prevalence of neural tube defects (NTDs) with peri-conceptional exposure to DTG. Here we explore whether a low folate diet influences the risk of DTG-associated foetal anomalies in a mouse model. C57BL/6 mice fed a folate-deficient diet for 2 weeks, were mated and then randomly allocated to control (water), or 1xDTG (2.5mg/kg), or 5xDTG (12.5mg/kg) both administered orally with 50mg/kg tenofovir disoproxil fumarate 33.3mg/kg emtricitabine. Treatment was administered once daily from gestational day (GD) 0.5 to sacrifice (GD15.5). Foetuses were assessed for gross anomalies. Maternal and foetal folate levels were quantified. 313 litters (103 control, 106 1xDTG, 104 5xDTG) were assessed. Viability, placental weight, and foetal weight did not differ between groups. NTDs were only observed in the DTG groups (litter rate: 0% control; 1.0% 1xDTG; 1.3% 5xDTG). Tail, abdominal wall, limb, craniofacial, and bleeding defects all occurred at higher rates in the DTG groups versus control. Compared with our previous findings on DTG usage in folate-replete mouse pregnancies, folate deficiency was associated with higher rates of several defects, including NTDs, but in the DTG groups only. We observed a severe left-right asymmetry phenotype that was more frequent in DTG groups than controls. Maternal folate deficiency may increase the risk for DTG-associated foetal defects. Periconceptional folic acid supplementation could be considered for women with HIV taking DTG during pregnancy, particularly in countries lacking folate fortification programs. This project has been funded by Federal funds from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN275201800001I and award #R01HD104553. LS is supported by a Tier 1 Canada Research Chair in Maternal-Child Health and HIV. HM is supported by a Junior Investigator award from the Ontario HIV Treatment Network.

Pregnancy characteristics and adverse outcomes in offspring of women with epilepsy: a prospective registry study from Mainland China.

This study aimed to explore the influencing factors of adverse outcomes in the offspring of women with epilepsy (WWE) and to analyze the changes brought about by the epilepsy knowledge popularization campaign in China (EKPCIC). This nested case-control study focused on WWE and their offspring from a female epilepsy cohort in mainland China. From January 2009 to August 2022, WWE was prospectively enrolled in 32 study centers. This study aimed to observe the health outcomes of their offspring within 1 year of age. The main outcome measure assessed the health status of the offspring within their first year of age. We aimed to analyze the effects of seizures, anti-seizure medicines (ASMs), and a lack of folic acid supplementation on adverse outcomes in the offspring of WWE and to explore the changes in perinatal management and adverse outcomes of the offspring after dissemination of the EKPCIC in 2015. Additionally, subgroup analyses were conducted to compare seizure control during pregnancy between the valproate and non-valproate groups. In total, 781 pregnancies in 695 WWE were included, of which 186 (23.69%) had adverse outcomes. The National Hospital Epilepsy Severity Scale score, number of seizures, status epilepticus, ASM type, and valproate and folic acid doses were associated with a high risk of adverse outcomes. After the EKPCIC, the use of ASMs (P = 0.013) and folic acid (P < 0.001), the seizure-free rate during pregnancy (P = 0.013), and the breastfeeding rate (P < 0.001) increased, whereas the incidence of complications during pregnancy decreased (P = 0.013). However, there was no significant difference in the incidence of adverse outcomes between the analyzed offspring pre-/post-EKPCIC. Additionally, there was no association between the frequency of seizures at different time points during pregnancy and the use of valproate (F = 1.514, P = 0.221). Possible factors influencing adverse outcomes in the offspring of WWE include seizures, type and number of ASM usage, and a lack of folic acid supplementation. Although the management of WWE during pregnancy is now more standardized, further efforts are needed to reduce adverse outcomes in offspring.

Association of Maternal Folate Intake and Offspring MTHFD1 and MTHFD2 Genes with Congenital Heart Disease.

Existing evidence supported that congenital heart defect (CHD) was associated with a combination of environmental and genetic factors. Based on this, this study aimed at assessing the association of maternal folic acid supplementation (FAS), genetic variations in offspring methylenetetrahydrofolate dehydrogenase (MTHFD)1 and MTHFD2 genes, and their interactions with CHD and its subtypes. A hospital-based case-control study, including 620 cases with CHD and 620 healthy children, was conducted. This study showed that the absence of FAS was significantly associated with an increased risk of total CHD and its subtypes, such as atrial septal defect (ASD). FAS during the first and second trimesters was associated with a significantly higher risk of CHD in offspring compared to FAS during the three months prior to conception. The polymorphisms of offspring MTHFD1 and MTHFD2 genes at rs2236222, rs11849530, and rs828858 were significantly associated with the risk of CHD. Additionally, a significantly positive interaction between maternal FAS and genetic variation at rs828858 was observed for the risk of CHD. These findings suggested that pregnant women should carefully consider the timing of FAS, and individuals with higher genetic risk may benefit from targeted folic acid supplementation as a preventive measure against CHD.

Nutrients deficiencies in patients with autism spectrum disorder, role of folic acid and vitamin D3 - review of literature

Introduction and purpose: This article will discuss the relationship between nutrition deficiency, focusing on folic acid and vitamin D3 and autism spectrum disorder (ASD). Research suggests that nutrient deficiencies play a role in the development and progression of autism. This article will investigate causes of nutrient deficiencies in ASD, like dietary constraints, food choice, and environment exposure, and their impact on ASD and related symptoms. The purpose of this article is to provide an overview of the research examining the relationship between folic acid and vitamin d3 supplementation and autism.&#x0D; Materials and methods: A broad search was conducted using the PubMed database in order to identify relevant studies published between 2010-2020 using keywords such as “folic acid”, “folinic acid”, "vitamin d3", "autism spectrum disorder".&#x0D; A brief description of the current state of knowledge: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that in recent years has been increasingly diagnosed among children. Only between 2016 and 2014 measured prevalence in the United States has increased by 10%. [1] The exact etiology of ASD in not known. In this review we will examine a role of folic acid and vitamin D3. Research suggests that folic acid supplements can help improve verbal skills in people with ASD. Research also shows decreased levels of vitamin d3 in ASD patients. Clinical trials involving vitamin d3 present inconclusive data but lean towards positive impact of supplementation. Both folic acid and vitamin d3 supplementation is safe. Dietary changes and oral supplementation may be beneficial for patients.&#x0D; Conclusions: Studies with larger participant numbers should be done to prove the significance of folic acid and vitamin D3 supplementation as it shows potential in being a safe and not expensive complementary therapeutic option.

Periconceptional intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further reduce the risk of neural tube defects in offspring: a United States population–based case-control study of women meeting the folic acid recommendations

BackgroundNeural tube defects (NTDs) still occur among some women who consume 400 μg of folic acid for prevention. It has been hypothesized that intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further protect against NTDs. ObjectivesTo investigate whether intakes of vitamin B6, vitamin B12, choline, betaine, methionine, thiamine, riboflavin, and zinc, individually or in combination, were associated with NTD risk reduction in offspring of women meeting the folic acid recommendations. MethodsData were from the National Birth Defects Prevention Study (United States population–based, case-control). We restricted deliveries between 1999 and 2011 with daily periconceptional folic acid supplementation or estimated dietary folate equivalents ≥400 μg. NTD cases were live births, stillbirths, or terminations affected by spina bifida, anencephaly, or encephalocele (n = 1227). Controls were live births without a major birth defect (n = 7095). We categorized intake of each micronutrient as higher or lower based on a combination of diet (estimated from a food frequency questionnaire) and periconceptional vitamin supplementation. We estimated NTD associations for higher compared with lower intake of each micronutrient, individually and in combination, expressed as odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, race/ethnicity, education, and study center. ResultsNTD associations with each micronutrient were weak to modest. Greater NTD reductions were observed with concurrent higher-amount intakes of multiple micronutrients. For instance, NTD odds were ∼50% lower among participants with ≥4 micronutrients with higher-amount intakes than among participants with ≤1 micronutrient with higher-amount intake (adjusted OR: 0.53; 95% CI: 0.33, 0.86). The strongest reduction occurred with concurrent higher-amount intakes of vitamin B6, vitamin B12, choline, betaine, and methionine (adjusted OR: 0.26; 95% CI: 0.09, 0.77) compared with ≤1 micronutrient with higher-amount intake. ConclusionsOur findings support that NTD prevention, in the context of folic acid fortification, could be augmented with intakes of methyl donors and other micronutrients involved in folate metabolism.