Folic Acid Supplement Use Research Articles

Letter to the editor: Comment on "Maternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: A cohort study"

Letter to the editor: Comment on "Maternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: A cohort study"

Folic acid allergy and the role of the basophil activation test

Background: Despite the large use of folic acid supplements, there are very few cases of reported allergy. Clinical case: A 38-year-old woman, experienced palmoplantar pruritus, generalized urticaria, angioedema and conjunctival hyperemia, 30 minutes after the intake of a 5mg folic acid tablet. She was taken to the Emergency Department and on discharge was referred to the Allergy and Clinical Immunology Department, where the patient underwent a diagnostic workup. The Skin Prick Test (SPT) was positive for the 5mg/mL concentration and the Basophil Activation Test (BAT) was considered positive for both dilutions, from an initial solution concentration of 5mg/ml: 1/100 dil (CD63=9.03%; SI=10.1) and 1/160 dil (CD63=7.46%; SI=8.4). Discussion/ Conclusion: We report a patient with an immediate reaction to folic acid with positive SPT and BAT, which favors an IgE-mediated allergy. To our knowledge, this is the first case describing the use of a BAT in the diagnostic workup of folic acid allergy.

Preconception Folic Acid and Multivitamin Supplementation for the Prevention of Neural Tube Defect: An Umbrella Review of Systematic Review and Meta-analysis.

Previous reviews explored the association between maternal use of folic acid and multivitamin supplements and risk of neural tube defect (NTD) in children, with no definitive conclusion. These reviews had produced contradictory results, and there had been no umbrella review. Therefore, the objective of this umbrella review is to combine the inconsistent data on the effect of prenatal folic acid and/or multivitamin supplementation for the prevention of NTD in offspring. Using the PRISMA guideline, PubMed, Embase, Scopus, Web of Sciences, Cochrane Database of Systematic Reviews, Scopus, and Google Scholar reported that the effects of folic acid and/or multivitamin supplementation for the prevention of NTD in offspring were searched. The quality of the included studies was assessed using Assessment of Multiple Systematic Reviews (AMSTAR). A weighted inverse variance random-effects model was applied to find the pooled estimates. The subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also assessed. Ten SRM with 296,816 study participants were included. The random-effects model analysis from 10 included systematic review and meta-analysis revealed that the pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD globally is found to be 0.43 (95% CI: 0.29, 0.58) (I2 = 93.50%; p ≤0.001). In the subgroup analysis, the pooled effect was found to be 0.23 (0.09, 0.37) in folic acid group, while this estimate is 0.63 (0.53, 0.72) and 0.61 (0.46, 0.75) in groups who took multivitamin. The pooled effect of prevention of NTD was found to be 0.50 (0.34, 0.66) in SRMs aimed at occurrence prevention (primary prevention) group, while this estimate is 0.20 (-0.01, 0.41) among SRMs, which aimed at reoccurrence (secondary) prevention, and 0.61 (0.46, 0.75) among those SRMs aimed to assess the effect folic acid or multivitamin for the prevention of both occurrence and reoccurrence. The pooled effect of either folic acid or multivitamin supplementation for the prevention of NTD was found to be 0.45 (0.03, 0.87) in SRMs of observational studies, while this estimate is 0.43 (0.32, 0.54) among SRMs of randomized controlled trials. This umbrella review of systematic review and meta-analysis found that prenatal folic acid and/or multivitamin supplementation was associated with a 57% reduction in NTD. Participants who took folic acid supplementation were associated with a slightly higher (77%) percentage of reduction in NTD compared with those who took multivitamin (37%). Reductions of 80% and 50% were observed for reoccurrence and occurrence prevention of NTD. Reductions of 57% and 55% of NTD have been found in SRM of RCTs and observational studies. This umbrella review revealed that both folic acid and multivitamin were associated with significantly lower levels of NTD in children. Considering the incorporation of those supplements in NTD prevention strategies during the preconception period is recommended. More large-scale prospective cohort and RCTs are needed to understand the protective effect of multivitamins and/or folic acid on NTD risk addressing the molecular mechanisms and to determine the optimal dose, duration, and timing of maternal multivitamin and folic acid intake for best child NTD risk reduction.

Folic acid supplementation is associated with a decreased mortality and reduced hospital readmission in patients with decompensated alcohol-related liver cirrhosis

Background and AimsThiamine and folic acid malnutrition is highly frequent in patients with decompensated alcohol-related liver cirrhosis (aLC). Current guidelines therefore recommend vitamin supplementation in these patients. However, implementation and its impact on the clinical outcome remains unknown. Therefore, we aimed to analyze the use of thiamine and folic acid and their effects on mortality and morbidity in patients with decompensated aLC. MethodsA number of 289 consecutive patients with decompensated aLC who received a paracentesis at Hannover Medical School between 2011 and 2023 were retrospectively investigated. The use of folic acid and thiamine-containing supplements was assessed in the discharge medication. Patients were followed for up to one year regarding liver transplant (LTx)-free survival and the incidence of hepatic encephalopathy, infections and hepatic decompensation requiring rehospitalization. ResultsMedian baseline MELD was 15, median age 56.6 years. 73.0% (n=211) were male patients. At hospital discharge, thiamine-containing supplements and folic acid were prescribed to 48.1% (n=139) and 18.0% (n=52) patients, respectively. Neither thiamine nor folic acid prescription were linked to improved clinical outcomes within 90 days. However, folic acid intake was associated with a higher one-year LTx-free survival (HR=0.48; p=0.04) in the multivariable analysis. Furthermore, folic acid substitution was linked to a decreased risk of rehospitalization within one year (HR=0.55; p=0.01) in the multivariable competing risk model. In contrast, thiamine prescription did neither affect LTx-free survival nor the here investigated liver-related complications. ConclusionFolic acid, but not thiamine substitution was linked to an improved outcome in patients with decompensated aLC.

Maternal non-compliance with recommended folic acid supplement use alters global DNA methylation in cord blood of newborns: A cohort study

Background & aimsPrenatal folate exposure may alter epigenetic marks in the offspring. We aimed to evaluate associations between prenatal exposure to folic acid (FA) in preconception and in utero with cord blood DNA methylation in long interspersed nuclear element 1 (LINE-1) and Alu short interspersed nuclear elements (SINEs) as markers of global DNA methylation levels. MethodsData come from 325 mother-child pairs participating in the Nutrition in Early Life and Asthma (NELA) birth cohort (2015-2018). Pregnant women were asked about supplement use, including brand name and dose, one month before pregnancy (preconception) and through the trimesters of pregnancy. Maternal dietary folate intake was assessed using a validated food frequency questionnaire with additional questions for FA supplement use. Folate serum levels were measured in mothers at 24 weeks of gestation and in cord blood of newborns. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 5 LINE-1 and 3 Alu different elements. Associations were estimated using multivariable linear regression models. ResultsA reduction in methylation levels of LINE-1 in newborns was associated with the use of FA supplements below the recommended doses (<400 ug/day) during preconception (-0.50; 95% CI: -0.91, -0.09; P=0.016), and from preconception up to 12 weeks of gestation (-0.48; 95% CI: -0.88, -0.08; P=0.018). Maternal use of FA supplements above the tolerable upper intake level of 1000 ug/day from preconception until 12 weeks of gestation was also related to lower methylation in LINE-1 at birth (-0.77; 95% CI: -1.52, -0.02; P=0.044). Neither FA supplement use after 12 weeks of gestation nor maternal total folate intake (diet plus supplements) were associated with global DNA methylation levels at birth. ConclusionsMaternal non-compliance with the use of FA supplement recommendations from preconception up to 12 weeks of gestation reduces offspring global DNA methylation levels at birth.

Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?

In the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression. The issue of masking and exacerbating B12 deficiency has recently been rekindled with the institution of folic acid fortification and the wide-spread use of folic acid supplements. The objectives of this review are to describe clinical and epidemiological evidence that excess folic acid exacerbates B12 deficiency, to summarize a hypothesis to explain this phenomenon, and to provide guidance for clinicians. Cognitive function test scores are lower and blood homocysteine and methylmalonic acid concentrations are higher in people with low B12 and elevated folate than in those with low B12 and nonelevated folate. High-dose folic acid supplementation in patients with pernicious anemia or epilepsy cause significant reductions in serum B12. It is hypothesized that high-dose folic acid supplements cause depletion of serum holotranscobalamin and thus exacerbate B12 deficiency. The evidence for excess folic acid exacerbating B12 deficiency is primarily correlative or from uncontrolled clinical observations, and the hypothesis to explain the phenomenon has not yet been tested. Nonetheless, the evidence is sufficiently compelling to warrant increased vigilance for identifying B12 deficiency in at risk individuals, including older adults and others with low B12 intake or conditions that are associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed folic acid in high doses.

Evaluation of nutritional status using the minimum dietary diversity for women of reproductive age (MDD-W) tool in breastfeeding mothers in Madagascar.

Women of reproductive age in low-income countries are especially nutritionally vulnerable given the strain that pregnancy and lactation places on the body. The aim of this study was to identify dietary diversity and its associated factors among mothers with young children. It is a cross-sectional study conducted in Ampefy, Madagascar from 1 November 2022 to 31 March 2023. Dietary diversity was determined using the minimum dietary diversity for women of reproductive age tool. Data were collected through face-to-face interviews using validated structured questionnaires, and anthropometric status was examined. Frequencies and percentages were calculated, and the comparison of variables was performed between mothers with acceptable and unacceptable dietary diversity using the chi-square test for qualitative variables. A logistic regression analysis was also conducted. A total of 437 mothers with young children participated in the study, resulting in a response rate of 95.0%. The mean age of the participants was 25.84 years (SD = 6.30). The study revealed that 32.95% of participants had unacceptable dietary diversity scores and the associated profile included low education, no transport, homebirth not by personal choice, not breastfeeding within the first hour of birth, not breastfeed exclusively for 6 months, no dietary changes during pregnancy or lactation, and no use of folic acid supplements. This study's findings underscore the importance of providing nutrition information to women, in order to improve dietary diversity and overall maternal and child health.

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

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

Folic acid and iodine supplement use from preconception through to six weeks postpartum in New Zealand women

Folic acid (FA) and iodine supplements are recommended by the Ministry of Health (MOH) for pregnant and/or lactating women in New Zealand (NZ)(1). Evidence suggests that many NZ women are not just taking FA and iodine in the form of a single-nutrient supplement (SNS) but are taking FA and iodine as part of a multivitamin supplement (MVS) which may or may not contain the recommended doses, and some are using a combination of both(2). No NZ study has examined the daily dose taken from both SNS and MVS for both FA and iodine across all time periods (2, 3). The aim of this study was to investigate what nutritional supplements containing FA and iodine were taken by postpartum NZ women, preconception, during the three trimesters of pregnancy and post-partum, and examine how well the women’s supplement use aligned with the NZ MOH recommendations. This cross-sectional observational study utilised data gathered on FA and iodine supplement use from an anonymous survey between February and August 2022. Descriptive statistics including frequency and percentages were reported. Folic acid and iodine weekly intakes from SNS and MVS were calculated by multiplying the amount of nutrient in each supplement, with the number of times per day taken, and the average number of days taken per week reported. A total of 584 women were included in the analysis. In addition to the SNS for FA (0.8mg and 5mg) and iodine (150 ug), women took 28 different MVS. Fifty-eight percent (preconception; 30% from SNS, 18% from MVS, and 10% from both) and 96% (1st trimester pregnancy; 61% from SNS, 17% from MVS, and 19% from both) of women took FA containing supplements. More than 75% of women reported taking iodine containing supplements during pregnancy (1st and 2nd trimesters: 93%, 3rd trimester: 89%) and postpartum (76%).Approximately 60% took SNS, 18% took only MVS and 14% took both. Based on the MOH recommendations, only 30% (preconception) and 62% (1st trimester) achieved sufficiency of FA supplementation at 0.8mg/day; 35% (preconception) and 69% (1st trimester) achieved sufficiency of FA at 5mg/day; around 50% women achieved sufficiency of iodine supplementation at 150 µg/day during pregnancy while only 37% during postpartum. The balance either took none, an insufficient dose or a dose that exceeded the recommended dose and many took them during non-recommended periods (FA after the 1st trimester; iodine preconception). Most women reported taking FA and/or iodine containing supplements at some point before, during and after their pregnancy. However, it is concerning that a large number of women do not seem to be adhering to the MOH recommendations for FA and iodine supplementation.

Prevalence of Urinary Tract Infection and Anemia and Their Associated Factors Among Pregnant Women

Background: Urinary tract infections (UTIs) and anemia are significant disorders that occur during pregnancy, potentially leading to severe complications. Objectives: This study explored the prevalence of urinary tract infections and anemia, along with their associated factors, among pregnant women. Methods: A cross-sectional retrospective study was conducted with 700 pregnant women attending clinics in Khash, Iran, in 2022. A self-administered questionnaire collected data on the socio-demographic and clinical factors of these women. The data were analyzed using descriptive statistics and the chi-square test in SPSS software, version 22. Multiple logistic regression models were used to calculate the adjusted odds ratio (AOR) with a 95% confidence interval (CI). Results: The prevalence rates of anemia and urinary tract infections were 63.6% (95% CI: 59.8 - 67.1) and 49% (95% CI: 45.2 - 52.7), respectively. Significant associations were observed between anemia and the number of medical care visits, smoking status, the use of iron and folic acid supplements, history of abortion, and thalassemia (P-value &lt; 0.05). Additionally, income level, previous history of urinary tract infections, education level, and syphilis were significantly associated with UTIs among pregnant women (P-value &lt; 0.05). Conclusions: The prevalence rates of anemia and UTIs among pregnant women are high. Consequently, standard antenatal care services, as recommended for the early identification of risk factors, should be emphasized by the Ministry of Health and its stakeholders to mitigate the high prevalence of anemia and UTIs during pregnancy and their associated complications.

Epigenetic Genome Modifications during Pregnancy: The Impact of Essential Nutritional Supplements on DNA Methylation.

Pregnancy is an extremely stressful period in a pregnant woman's life. Currently, women's awareness of the proper course of pregnancy and its possible complications is constantly growing. Therefore, a significant percentage of women increasingly reach for various dietary supplements during gestation. Some of the most popular substances included in multi-ingredient supplements are folic acid and choline. Those substances are associated with positive effects on fetal intrauterine development and fewer possible pregnancy-associated complications. Recently, more and more attention has been paid to the impacts of specific environmental factors, such as diet, stress, physical activity, etc., on epigenetic modifications, understood as changes occurring in gene expression without the direct alteration of DNA sequences. Substances such as folic acid and choline may participate in epigenetic modifications by acting via a one-carbon cycle, leading to the methyl-group donor formation. Those nutrients may indirectly impact genome phenotype by influencing the process of DNA methylation. This review article presents the current state of knowledge on the use of folic acid and choline supplementation during pregnancy, taking into account their impacts on the maternal-fetal unit and possible pregnancy outcomes, and determining possible mechanisms of action, with particular emphasis on their possible impacts on epigenetic modifications.

Women in Canada are consuming above the upper intake level of folic acid but few are meeting dietary choline recommendations in the second trimester of pregnancy: data from the CHILD cohort study.

There is concern that during a low-risk pregnancy, women are consuming more than recommended (400 µg/day) supplemental folic acid and may not meet recommendations for other nutrients. The objective of this study was to determine folic acid supplement use and dietary folate intakes in the second trimester (week 18) of pregnancy in women (n=2996) in the Canadian CHILD cohort study. Vitamin B12 and choline intakes were also assessed because they are metabolically related to folate. The majority of participants (71.6%) were consuming a daily prenatal supplement. Twenty-eight percent of women (n=847) reported consuming a folic acid supplement and of these women, 45.3% had daily supplemental folic acid intakes above the upper intake level (UL; 1000 µg/day). Daily dietary folate intakes were (mean (SD)) 575 (235) DFE µg/day. In contrast, only 24.8% of women met the dietary choline adequate intake (AI) recommendation (AI ≥ 450mg/day) with a mean (SD) intake of 375 (151) mg/day. Further understanding of the impact of supplemental folic acid intake above the UL and low choline intake during pregnancy requires further investigation.

Somali immigrant women’s knowledge of and experiences with folic acid supplement use before and during pregnancy: A qualitative study from Norway

IntroductionHealth authorities in many countries recommend that women should take folic acid supplements before and during pregnancy to prevent having babies with neural tube defects. Somali immigrant women in Norway use less folic acid supplements than the recommended amount and subsequently, less than Norwegian-born women. ObjectivesTo explore Somali immigrant women’s knowledge of and experiences with using folic acid supplements before and during pregnancy. MethodsData were collected through semi-structured individual interviews with ten Somali immigrant women in Norway. The participants were recruited and interviewed between September and November 2019. Graneheim and Lundmańs qualitative content analysis was used for data analysis. ResultsTwo main themes were developed through the process of analysing the data: 1) Attitudes to life and pregnancy affect how health care advice is met; 2) Understanding the benefits of folic acid is crucial. ConclusionsThe women in this study had varied knowledge about, and experiences with the use of folic acid supplements before and during pregnancy. The findings suggest that the healthcare system needs to adapt the information it provides on folic acid supplementation to target the needs of Somali immigrant women. In line with suggestions from the study participants, information needs to be given in a timely manner, by someone they trust, in their first language, include visual aids, and be offered to all women of childbearing age before their first pregnancy.

Factors Associated with the use of Folic Acid and Iron Supplementation in the Periconceptional and Antenatal Periods of Pregnant Women: A Cross-Sectional Study

Factors Associated with the use of Folic Acid and Iron Supplementation in the Periconceptional and Antenatal Periods of Pregnant Women: A Cross-Sectional Study

Factors Influencing Folic Acid and Iron Supplement Use Among Pregnant Women at Hoima Regional Referral Hospital in Uganda

The study sought to assess adherence levels to Folic Acid and Iron supplementation among expectant women attending antenatal care at Hoima Regional Referral Hospital. Findings revealed a 58.8% adherence rate among pregnant mothers. Among adherents, the majority were younger than 30, Christians, rural residents, cohabiting, had primary education, and were homemakers. Notably, only a minority were experiencing their first pregnancy. Regarding awareness and advice, a significant percentage knew about the preventive benefits of Iron-folic acid supplements against anemia, had received advice on supplementation benefits and the necessity of not missing doses. However, awareness about the specific benefits, dosage, and sources of folic acid and iron was limited. While most attended early ANC visits, only a fraction knew about folic acid benefits and sources, the correct dosage, or foods containing folic acid. Additionally, just over half met the recommended ANC visit frequency. Factors influencing adherence were largely tied to demographics such as age, religion, residence, partnership status, education, and employment, alongside knowledge gaps about supplementation benefits and dosages. Conversely, behaviors like alcohol intake, late or infrequent ANC attendance, and negative experiences during ANC acted as barriers to adherence. Keywords: Pregnancy, Anaemia, Antenatal Care, Folic acid, Iron supplementation.

Folic acid supplementation use during the peri-conceptional period among professionals of a hospital in France

Folic acid insufficiency is an important risk factor for congenital neural tube defects. Despite recommendations and national campaigns, the proportion of women taking folic acid in the peri-conceptional period remains insufficient worldwide. We describe in this study the proportion of peri-conceptional folic acid supplementation use and its determinants among a population of hospital workers during the course of a prevention campaign. We performed a single-center cross sectional study in a university hospital in France. Data were collected during 2 months in 2019 by an online questionnaire sent to all professionals. We collected information about folic acid supplementation use, its modalities (form, period, frequency and dosage) and reason for initiating or not supplementation. Response rate was 11.4 % (n = 1,075/9,447). Among the 748 women who reported at least one pregnancy, 72.7 % (95 % CI: 69.4–76.0 %) reported taking folic acid during their last pregnancy. Main reason for initiating supplementation was information given by a health professional (87.8 %), especially by gynaecologists-obstetricians. Principal factors associated with folic acid supplementation use were age between 25 and 35 years, high level of education and recent pregnancy. Folic acid supplementation use is still not systematic before and during pregnancy, even among health professionals. There is a case for mandatory folic acid fortification for the French general population.

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.

Frequency of Various Congenital Anomalies and Associated Maternal Risk Factors, an Experience at Tertiary Care Hospital

Objective: To determine frequency of congenital anomalies in children and associated risk factors of mothers. Setting: Department of obstetrics and gynecology Rai Medical College Sargodha. Study design: Descriptive observational study. Duration: July 2022 to December 2022. Methodology: All babies with congenital anomalies born within study duration and their mothers were included in this study. Anomalies of neonates were evaluated after proper clinical evaluation by a neonatologist. A questionnaire was designed to evaluate maternal risk factors. All collected data was analyzed using SPSS version 20. Results: Total 1900 babies delivered during this study period and out of them congenital anomalies were found in 31 (1.6%) cases. Most common anomaly was hydrocephalus in 10(32.2%) and meningomyelocele in 6(19.3%) cases. Most common maternal risk factor was consanguineous marriage in 15(48.3%) cases. Most commonly mothers with the age of 19-30 years were having babies with congenital anomalies. Practical Implication: This study helps us to understand the importance of avoiding consanguineous marriages, screening of high risk cases using various diagnostic techniques like ultrasonography during 16-20 weeks, use of folic acid supplements and in case of detecting congenital anomalies option of selective termination of pregnancy can be offered to the parents. Proper awareness of the parents and their counselling after birth of a baby with anomaly can prevent its recurrence in their future pregnancies Conclusion: Most common congenital anomaly reported in this study was hydrocapahlus followed by meningocele and most common maternal risk factor associated with these anomalies was consanguineous marriage. Keywords: Congenital anomaly, consanguineous marriage, Maternal risk factor, Neural tube defects

Pregnancy, folic acid, and antiseizure medication

Abstract Background Although some antiseizure medications (ASMs) are teratogenic, most people with epilepsy need treatment in pregnancy. The risk of ASM fetotoxicity may be mitigated with folic acid. High-dose folic acid supplementation has traditionally been recommended before and during gestation despite little evidence of efficacy and safety for this patient group. Several studies have investigated the potential benefits and risks of folic acid supplements. Objective To provide an updated overview of the risks, benefits, and rationale for use of folic acid supplementation in relation to pregnant people of childbearing age using ASM. Materials and methods This is a narrative review based on an unstructured literature search of PubMed. We also scrutinized neurological and obstetrical guidelines. Results Antiseizure medication can decrease folate concentrations. In children exposed to ASM prenatally, those born to persons using folic acid supplements periconceptionally had lower risk of adverse neurodevelopment and preterm birth. It remains unclear whether the risk for congenital malformations can be equally alleviated. In studies of the general population, high plasma folate concentrations and/or high-dose folic acid supplements were associated with adverse neurodevelopmental outcomes. This has not been seen in children of mothers with epilepsy. However, an increased cancer risk has been found in children of mothers with epilepsy using high-dose folic acid supplements in pregnancy. Conclusion The optimal folic acid dose is not clear for persons of childbearing potential with epilepsy using ASM. Both low and excess folate status during pregnancy have been associated with adverse neurodevelopment. We propose an individual folic acid supplement dose that should be titrated based on maternal plasma folate concentrations during pregnancy.

Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?

BackgroundPrenatal exposure to antiseizure medication (ASM) may lead to low plasma folate concentrations and is associated with impaired neurodevelopment. ObjectivesTo examine whether maternal genetic liability to folate deficiency interacts with ASM-associated risk of language impairment and autistic traits in children of women with epilepsy. MethodsWe included children of women with and without epilepsy and with available genetic data enrolled in the Norwegian Mother, Father, and Child Cohort Study. Information on ASM use, folic acid supplement use and dose, dietary folate intake, child autistic traits, and child language impairment was obtained from parent-reported questionnaires. Using logistic regression, we examined the interaction between prenatal ASM exposure and maternal genetic liability to folate deficiency expressed as polygenic risk score of low folate concentrations or maternal rs1801133 genotype (CC or CT/TT) on risk of language impairment or autistic traits. ResultsWe included 96 children of women with ASM-treated epilepsy, 131 children of women with ASM-untreated epilepsy, and 37,249 children of women without epilepsy. The polygenic risk score of low folate concentrations did not interact with the ASM-associated risk of language impairment or autistic traits in ASM-exposed children of women with epilepsy compared with ASM-unexposed children aged 1.5–8 y. ASM-exposed children had increased risk of adverse neurodevelopment regardless of maternal rs1801133 genotype {adjusted odds ratio [aOR] for language impairment aged 8 y was 2.88 [95% confidence interval (CI): 1.00, 8.26] if CC and aOR 2.88 [95% CI: 1.10, 7.53] if CT/TT genotypes}. In children of women without epilepsy aged 3 y, those with maternal rs1801133 CT/TT compared with CC genotype had increased risk of language impairment (aOR: 1.18; 95% CI: 1.05, 1.34). ConclusionsIn this cohort of pregnant women reporting widespread use of folic acid supplements, maternal genetic liability to folate deficiency did not significantly influence the ASM-associated risk of impaired neurodevelopment.