Tube Defects In Infants Research Articles

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

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

Low-dose daily folic acid (400 μg) supplementation does not affect regulation of folate transporters found present throughout the terminal ileum and colon of humans: a randomized clinical trial

BackgroundFolic acid supplementation during the periconceptional period reduces the risk of neural tube defects in infants, but concern over chronic folic acid exposure remains. An improved understanding of folate absorption may clarify potential risks. Folate transporters have been characterized in the small intestine, but less so in the colon of healthy, free-living humans. The impact of folic acid fortification or supplementation on regulation of these transporters along the intestinal tract is unknown. ObjectiveThe objective was to characterize expression of folate transporters/receptor (FT/R) and folate hydrolase, glutamate carboxypeptidase II (GCPII), from the terminal ileum and throughout the colon of adults and assess the impact of supplemental folic acid. MethodsIn this 16-wk open-labeled randomized clinical trial, adults consumed a low folic acid-containing diet, a folate-free multivitamin, and either a 400 μg folic acid supplement or no folic acid supplement. Dietary intakes and blood were assessed at baseline, 8 wk, and 16 wk (time of colonoscopy). Messenger RNA (mRNA) expression and protein expression of FT/R and GCPII were assessed in the terminal ileum, cecum, and ascending and descending colon. ResultsAmong 24 randomly assigned subjects, no differences in dietary folate intake or blood folate were observed at baseline. Mean ± SD red blood cell folate at 16 wk was 1765 ± 426 and 911 ± 242 nmol/L in the 400 and 0 μg folic acid group, respectively (P < 0.0001). Reduced folate carrier, proton-coupled folate transporter, and folate-receptor alpha expression were detected in the terminal ileum and colon, as were efflux transporters of breast cancer resistance protein and multidrug resistance protein-3. Other than a higher mRNA expression of FR-alpha and GCPII in the 400 μg supplement group in the ascending colon, no treatment differences were observed (P < 0.02). ConclusionsFolate transporters are present throughout the terminal ileum and colon; there is little evidence that a low dose of folic acid supplementation affects colonic absorption.This trial was registered at clinicaltrials.gov as NCT03421483.

Dolutegravir-induced neural tube defects in mice are folate responsive.

In 2018, the Botswana Tsepamo Study reported a nine-fold increased risk of neural tube defects in infants whose mothers were treated with dolutegravir (DTG) from the time of conception. As maternal folate supplementation and status is a well known modifier of neural tube defect (NTD) risk, we sought to evaluate birth outcomes in mice fed normal and low folic acid diets treated with DTG during pregnancy. DTG was evaluated for developmental toxicity using pregnant mice fed normal or low folic acid diet. CD-1 mice were provided diet with normal (3 mg/kg) or low (0.3 mg/kg) folic acid. They were treated with water, a human therapeutic-equivalent dose, or supratherapeutic dose of DTG from mouse embryonic day E6.5 to E12.5. Pregnant dams were sacrificed at term (E18.5) and fetuses were inspected for gross, internal, and skeletal defects. Fetuses with exencephaly, an NTD, were present in both therapeutic human equivalent and supratherapeutic exposures in dams fed low folic acid diet. Cleft palates were also found under both folate conditions. Recommended dietary folic acid levels during mouse pregnancy ameliorate developmental defects that arise from DTG exposure. Since low folate status in mice exposed to DTG increases the risk for NTDs, it is possible that DTG exposures in people living with HIV with low folate status during pregnancy may explain, at least in part, the elevated NTD risk signal observed in Botswana. Based on these results, future studies should consider folate status as a modifier for DTG-associated NTD risk.

Awareness of Vitamin and mineral supplements among college students.

A Vitamin or mineral supplement is a kind of adjunct that aims to supplement the diet and it comprises a wide range of Vitamins, minerals, herbs, etc., that amplifies different nutrient levels. People intake such supplements for protection against health illnesses such as stress, cold, flu, osteoporosis, heart attacks, tooth decay, cancer, and neural tube defects in infants, etc. Anyhow, intake of large amounts without proper medical consideration can have severe negative consequences. This study aimed to assess the awareness on Vitamin and mineral supplements among College students. An online cross-sectional questionnaire was made using Google Forms and distributed among 100 College students. The data collected were analyzed using SPSS software. Descriptive analysis and Chi-square tests were done. Results showed that the majority of 63.43% of UG students and 21.64% of PG students believed that its consumption was beneficial and in general awareness was more among UG students. When asked about the Vitamin that should be avoided during pregnancy, a majority of 20.30% of UG students opted for Vitamin E and 7.52% of PG students opted for Vitamin A which shows that both were feasible options as they were fat-soluble vitamins capable of causing congenital defects. The most probable issue related with the use of dietary supplements is that the people who include them in their diet might see it as a substitute, in lieu of a supplement, thus, more people should be made aware of the proper consumption and side effects of Vitamin and mineral supplements.

周産期の医薬品使用の安全性に関する研究

We have been conducting research with the aim of generating evidence for the safety of perinatal drugs. As a result of reviewing the records of inquiries to the Drug Information Office of our hospital, we found a large discrepancy between the description of perinatal drugs in package inserts in Japan and the description of the Pregnancy Risk Category according to the U.S. Food and Drug Administration. In the Japan Environment and Children's Study (JECS), we determined the proportion of drug and supplement use among 97464 pregnant women. We clarified that prescriptions of antihypertensive drugs for pregnant women increased during the second half of pregnancy, while prescriptions of anti-epileptic and anti-anxiety drugs decreased after pregnancy using a claims database. A survey of pharmacists and pharmacy students revealed a lack of awareness of effective folic acid intake to reduce the risk of neural tube defects in infants. The percentage of pre-pregnancy folic acid supplementation among pregnant women participating in the Babies and their Parents' Longitudinal Observation in Suzuki Memorial Hospital on Intrauterine Period (BOSHI) study, the JECS, and the Tohoku Medical Megabank (TMM) Birth and Three-Generation (BirThree) cohort study was 6.3-18.0%. As a result of close examination of the records of inquiries to the Drug Information Office of our hospital, and of cases in which our lactation plan sheet was applied, it was found that there were discrepancies between the information on the drug package insert and the information on Medications & Mother's Milk, etc. in Japan. The results obtained have been clinically applied in daily practice and we are continuing our research while taking measures.

Validity of diagnosis and procedure codes for identifying neural tube defects in infants.

The use of validated criteria to identify birth defects in electronic healthcare databases can avoid the cost and time-intensive efforts required to conduct chart reviews to confirm outcomes. This study evaluated the validity of various case-finding methodologies to identify neural tube defects (NTDs) in infants using an electronic healthcare database. This analysis used data generated from a study whose primary aim was to evaluate the association between first-trimester maternal prescription opioid use and NTDs. The study was conducted within the Medication Exposure in Pregnancy Risk Evaluation Program. A broad approach was used to identify potential NTDs including diagnosis and procedure codes from inpatient and outpatient settings, death certificates and birth defect flags in birth certificates. Potential NTD cases were chart abstracted and confirmed by clinical experts. Positive predictive values (PPVs) and 95% confidence intervals (95% CI) are reported. The cohort included 113 168 singleton live-born infants: 55 960 infants with opioid exposure in pregnancy and 57 208 infants unexposed in pregnancy. Seventy-three potential NTD cases were available for the validation analysis. The overall PPV was 41% using all diagnosis and procedure codes plus birth certificates. Restricting approaches to codes recorded in the infants' medical record or to birth certificate flags increased the PPVs (72% and 80%, respectively) but missed a substantial proportion of confirmed NTDs. Codes in electronic healthcare data did not accurately identify confirmed NTDs. These results indicate that chart review with adjudication of outcomes is important when conducting observational studies of NTDs using electronic healthcare data.

Mutational landscape screening of methylene tetrahydrofolate reductase to predict homocystinuria associated variants: An integrative computational approach

Methylene tetrahydrofolate reductase (MTHFR) is a flavoprotein, involved in one-carbon pathway and is responsible for folate and homocysteine metabolism. Regulation of MTHFR is pivotal for maintaining the cellular concentrations of methionine and SAM (S-adenosyl methionine) which are essential for the synthesis of nucleotides and amino acids, respectively. Therefore, mutations in MTHFR leads to its dysfunction resulting in conditions like homocystinuria, cardiovascular diseases, and neural tube defects in infants. Among these conditions, homocystinuria has been highly explored, as it manifests ocular disorders, cognitive disorders and skeletal abnormalities. Hence, in this study, we intend to explore the mutational landscape of human MTHFR isoform-1 (h.MTHFR-1) to decipher the most pathogenic variants pertaining to homocystinuria. Thus, a multilevel stringent prioritization of non-synonymous mutations in h.MTHFR-1 by integrative machine learning approaches was implemented to delineate highly deleterious variants based on its pathogenicity, impact on structural stability and functionality. Subsequently, extended molecular dynamics simulations and molecular docking studies were also integrated in order to prioritize the mutations that perturbs structural stability and functionality of h.MTHFR-1. In addition, displacement of Loop (Arg157-Tyr174) and helix α9 (His263-Ser272) involved in open/closed conformation of substrate binding domain were also probed to confirm the functional loss. On juxtaposed analysis, it was inferred that among 126 missense mutations screened, along with known pathogenic mutations (H127 T, A222 V, T227 M, F257 V and G387D) predicted that W500C, P254S and D585 N variants could be potentially driving homocystinuria. Thus, uncovering the prospects for inclusion of these mutations in diagnostic panels based on further experimental validations.

Congenital anomalies following antenatal exposure to dolutegravir: a Canadian surveillance study.

Dolutegravir is recommended worldwide as a first-line antiretroviral therapy (ART) for individuals living with HIV. A recent study reported increased rates of neural tube defects in infants of dolutegravir-treated women. This study examined rates of congenital anomalies in infants born to women living with HIV (WLWH) in Canada. The Canadian Perinatal HIV Surveillance Programme captures surveillance data on pregnant WLWH and their babies and was analysed to examine the incidence of congenital anomalies. Paediatric HIV clinics. Live-born infants born in Canada to WLWH between 2007 and 2017. Data on mother-infant pairs, including maternal ART use at conception and during pregnancy, are collected by participating sites. Congenital anomalies. Of the 2423 WLWH, 85 (3.5%, 95% CI 2.85-4.36%) had non-chromosomal congenital anomalies. There was no evidence of a significant difference in rates of congenital anomalies between women who were on ART in their first trimester (3.9%, CI 1.7-7.6%) or later in the pregnancy (3.9%, 95% CI 2.6-5.6%). Four of the 80 (5.0%, 95% CI 1.4-12.3%) neonates born to WLWH on dolutegravir during the first trimester had congenital anomalies, none were neural tube defects (95% CI 0.00-3.10%). Despite recent evidence raising a safety concern, this analysis found no signal for increased congenital anomalies. Five percent of the infants of Canadian women living with HIV on dolutegravir at conception had congenital anomalies; none had neural tube defects.

CARACTERÍSTICAS EPIDEMIOLÓGICAS DAS ANOMALIAS CONGÊNITAS DO TUBO NEURAL EM MENORES DE 5 ANOS DE IDADE E POSSÍVEIS FATORES DE RISCO PARA A SUA OCORRÊNCIA EM CAMPOS DOS GOYTACAZES-RJ

As anomalias congênitas, possuem etiologia multifatorial, envolvendo aspectos genéticos e ambientais. Entre diversos fatos geradores, é evidente a importância do ácido fólico na redução ou mesmo prevenção de malformações. Esta vitamina relaciona-se com a síntese de DNA e RNA, portanto, com o desenvolvimento fetal. Foi implementada no País a fortificação compulsória das farinhas de trigo e milho com ferro e ácido fólico resultando em redução de anomalias em 35%. Já níveis diários de suplementação medicamentosa superiores a 5mg de ácido fólico reduz entre 75% e 91%. Tal fato demonstra a relevância e benefícios do folato no pré-natal. O período ideal de administração seria o periconcepcional, de 1 a 3 meses antes da gestação e até 4 meses após a concepção. Este estudo objetiva avaliar a prevalência de Anomalias Congênitas do tubo neural de menores de 5 anos de idade no município de Campos dos Goytacazes-RJ, através de um estudo de caso controle para serem analisados possíveis fatores de risco para ocorrência de tais anormalidades. Para análise da distribuição de defeitos do tubo neural foram usadas as variáveis: nível socioeconômico e educacional, idade materna, utilização ou não do ácido fólico, realização de pré-natal, número de consultas, entre outras. A amostra coletada é do tipo probabilística aleatória simples, período de realização, 1º de março de 2016 à 30 de maio de 2017. Este projeto atenderá a resolução 196/96 versão 2012 do CNS relativas ás questões da ética em pesquisa com humanos.&#x0D;

The occurrence and co-occurrence of aflatoxin and fumonisin along the maize value chain in southwest Nigeria

Aflatoxin and fumonisin are two major foodborne mycotoxins: toxic chemicals produced by fungi that contaminate food commodities including maize, a staple food in sub-Saharan Africa. Aflatoxin causes liver cancer, and is associated with acute liver toxicity and immunotoxicity; while fumonisin is associated with neural tube defects in infants and esophageal cancer. Both mycotoxins have been associated with child growth impairment. Previous studies suggest that co-occurrence of these mycotoxins may have potentially synergistic toxicological effects. Despite health risks associated with co-occurrence of these mycotoxins, no study has examined their co-occurrence along key food supply chains in Africa. This study is the first report that examines the occurrence and co-occurrence of aflatoxins and fumonisins along the maize value chain in Nigeria. All samples were analyzed using LC-MS/MS. About 52% and 21% of the samples had aflatoxin levels above the Nigerian and US standards for human food, respectively. Though no regulatory limits exist for fumonisin in Nigeria, 13% of the samples contained fumonisin levels higher than the US regulatory limit. Aflatoxin levels can become dangerously high in maize stored four months or longer. Adequately addressing mycotoxin risk requires consideration of the entire maize value chain and associated value chains for food production.

Outcome of Choroid Plexus Cauterization with Endoscopic 3&amp;lt;sup&amp;gt;rd&amp;lt;/sup&amp;gt; Ventriculostomy vs Ventricular Shunting in Management of Hydrocephalus Secondary to Neural Tube Defect

Background: Different surgical management of infants suffering neural tube defects (NTD) associated hydrocephalus were reported in the literature. Great debate whether combining endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) is more effective than ventriculoperitoneal (VP) shuntfor management of congenital hydrocephalus secondary to neural tube defects ininfants younger than 1 year of age. Purpose: To evaluate and compare the therapeutic efficacy of ETV combined with CPC versus VP shunts in infants with infantile hydrocephalus associated with NTD. Methods: Thirty infants with infantile NTD associated hydrocephalus (de novo), were equally divided and randomly allocated to each intervention group either ETV/CPC or VP shunts). They were monitored for at least 6 months for any sign of raised intracranial pressure (rICP) and/or hydrocephalic metrics (fontanelle quality, HC, and ventricular size) were also documented and compared between two groups. Statistical Analysis: The association between intervention group and outcome was tested with Chi-square test and P=0.05 or less was considered statistically significant. Results: Of the total thirty patients included in the study, thirteen patients (43.3%) were male and seventeen were female (56.7%) with mean age of 80.3±11.5 days. Twenty patients (66%) were under 6 months of age. The overall success rate in 1-year follow-up was 54% and 60% for VP shunt and ETV/CPC, respectively; with the difference being not statistically significant. Conclusion: Combined ETV-CPC is considered a successful surgical option for treatment of infantile hydrocephalus associated with NTD; achieving success rate better than VPS implantation.

Risks and benefits of dolutegravir-based antiretroviral drug regimens in sub-Saharan Africa: a modelling study

SummaryBackgroundThe integrase inhibitor dolutegravir could have a major role in future antiretroviral therapy (ART) regimens in sub-Saharan Africa because of its high potency and barrier to resistance, good tolerability, and low cost, but there is uncertainty over appropriate policies for use relating to the potential for drug resistance spread and a possible increased risk of neural tube defects in infants if used in women at the time of conception. We used an existing individual-based model of HIV transmission, progression, and the effect of ART with the aim of informing policy makers on approaches to the use of dolutegravir that are likely to lead to the highest population health gains.MethodsWe used an existing individual-based model of HIV transmission and progression in adults, which takes into account the effects of drug resistance and differential drug potency in determining viral suppression and clinical outcomes to compare predicted outcomes of alternative ART regimen policies. We calculated disability adjusted life-years (DALYs) for each policy, assuming that a woman having a child with a neural tube defect incurs an extra DALY per year for the remainder of the time horizon and accounting for mother-to-child transmission. We used a 20 year time horizon, a 3% discount rate, and a cost-effectiveness threshold of US$500 per DALY averted.FindingsThe greatest number of DALYs is predicted to be averted with use of a policy in which tenofovir, lamivudine, and dolutegravir is used in all people on ART, including switching to tenofovir, lamivudine, and dolutegravir in those currently on ART, regardless of current viral load suppression and intention to have (more) children. This result was consistent in several sensitivity analyses. We predict that this policy would be cost-saving.InterpretationUsing a standard DALY framework to compare health outcomes from a public health perspective, the benefits of transition to tenofovir, lamivudine, and dolutegravir for all substantially outweighed the risks.FundingBill & Melinda Gates Foundation.

Risk factors associated with neural tube defects in infants referred to western Iranian obstetrical centers; 2013-2014.

BackgroundNeural tubes defects (NTDs) are known to be the second most prevalent congenital disorder worldwide whose risk factors have not been explicitly addressed yet.AimTo determine the risk factors affecting NTDs among infants who referred to obstetrical centers in Kurdistan, a western province of Iran.MethodsThis prospective case-control study was conducted in the form of prospective case-control. Sample population included all women (27,153 cases) who referred to obstetrical centers in Kurdistan for either delivery or abortion during 2013 and 2014. Inclusion criterion was the presence of a known NTD in infants, and exclusion criterion was the reluctance of patients to participate in the study. Accordingly, 46 cases participated in the study as the case group, and 138 cases (three times higher than case group) were selected to be the control group. Case and control groups were matched in terms of the number of pregnancies and place of birth. The variables investigated in the present study were as follows: age, occupation, BMI, abortion history, family relation with husband, fetus’ sex, number of twins, history of previous children with NTD, receiving prenatal surveillance, consumption of folic acid and multivitamins, smoking, alcohol drinking, passive smoking, and suffering from such diseases as epilepsy and diabetes. Data were analyzed using various statistical tests, including chi-square, Fishers’ exact test, multiple logistic regression analysis using SPSS version 20. In the study group, inclusion criteria included all women who had an infant with tube defects that their total number was 46 individuals. In the control group inclusion criteria included mothers with healthy infants who were similar to the study group in terms of birth place and frequency of pregnancy.ResultsThe results of the present study demonstrated that prenatal surveillance (p<0.002), multivitamin consumption (p<0.001), history of having a child with NTD (p<0.001), alcohol drinking (p<0.014), and passive smoking were related to NTDs (p<0.001).ConclusionBefore fertilization and during pregnancy, mothers should be examined in terms of exposure to harmful agents, diet, and nutritional status in order to identify possible risk factors and find opportunities to prevent NTDs in infants.

Formation of neurodegenerative aggresome and death-inducing signaling complex in maternal diabetes-induced neural tube defects

Diabetes mellitus in early pregnancy increases the risk in infants of birth defects, such as neural tube defects (NTDs), known as diabetic embryopathy. NTDs are associated with hyperglycemia-induced protein misfolding and Caspase-8-induced programmed cell death. The present study shows that misfolded proteins are ubiquitinylated, suggesting that ubiquitin-proteasomal degradation is impaired. Misfolded proteins form aggregates containing ubiquitin-binding protein p62, suggesting that autophagic-lysosomal clearance is insufficient. Additionally, these aggregates contain the neurodegenerative disease-associated proteins α-Synuclein, Parkin, and Huntingtin (Htt). Aggregation of Htt may lead to formation of a death-inducing signaling complex of Hip1, Hippi, and Caspase-8. Treatment with chemical chaperones, such as sodium 4-phenylbutyrate (PBA), reduces protein aggregation in neural stem cells in vitro and in embryos in vivo. Furthermore, treatment with PBA in vivo decreases NTD rate in the embryos of diabetic mice, as well as Caspase-8 activation and cell death. Enhancing protein folding could be a potential interventional approach to preventing embryonic malformations in diabetic pregnancies.

Folic acid supplementation in pregnancy and implications in health and disease.

Maternal exposure to dietary factors during pregnancy can influence embryonic development and may modulate the phenotype of offspring through epigenetic programming. Folate is critical for nucleotide synthesis, and preconceptional intake of dietary folic acid (FA) is credited with reduced incidences of neural tube defects in infants. While fortification of grains with FA resulted in a positive public-health outcome, concern has been raised for the need for further investigation of unintended consequences and potential health hazards arising from excessive FA intakes, especially following reports that FA may exert epigenetic effects. The objective of this article is to discuss the role of FA in human health and to review the benefits, concerns and epigenetic effects of maternal FA on the basis of recent findings that are important to design future studies.

Folic Acid Food Fortification and Incidence of Anemia In General Population

AbstractAbstract 5140 Introduction:Folic acid (FA) deficiency is considered one of the important causes of anemia and of neural tube defects in infants. In 1996 FDA issued a regulation that by 1998 all enriched grain products contain 140 mg of folic acid per 100 grams. This process began in 1996 and was essentially completed by mid-1997. This program intended to increase folic acid intake among women of childbearing age has decreased the incidence of pregnancies affected by neural tube defects. This has also led to a decrease in incidence of FA as a cause of anemia. In 2000 we reported the impact of folate food fortification in our community hospital. In 1994 to 1996, of 4403 patients sample tested 60 were found to be folate deficient. From 1997 to 1999 only 3 of 6326 patients tested were folate deficient. The first patient was 73 year old and had severe CHF and COPD, the second patient was 62 year old alcoholic admitted with delirium tremens, and third patient was 90 year old with dysphagia who required PEG replacement. All three appeared to have stopped eating in the days prior to admission. On the basis of this experience in our community hospital we concluded at that time that folate food fortification has largely eliminated FA deficiency and that the routine determination of FA as part of anemia work up in this era is not indicated. We now report our continuing experience from 2003 to 2006. Methods:We studied retrospectively the patients who presented in our community hospital with anemia and folate level ordered as a part of anemia work up. Serum folate levels were measured using Bayer Center Chemiluminescent Assay. Serum FA level <1.1 mg/ml is considered indicative of deficiency. We evaluated 1861 patients from year January'2003 to May'2006. We also assessed the cost effectiveness of ordering this test routinely as part of anemia workup. Results:Among the 1861 patients, we did not find any patient who had folate level of less than 1.1, which is the lower limit for folate level in our laboratory. Medicare cost for serum folate level test for our institute is $20.54 (code 82746) and phlebotomy cost for one test is $3.00 (code 36418). Total cost for this test for one patient is $23.54. Total health cost for these tests in 3 years and five months was $43807.94. Conclusion:Our results which are similar to our previous report suggest that food fortification and possibly also vitamin supplementation has substantially improved blood folate levels and has largely eliminated folic acid deficiency as a cause of anemia in the population that we tested. Routine folate level determination in the workup of anemia is not cost effective and may be best limited in patients who are malnourished as in patients with poor nutrition status, malabsorption, alcoholics and psychiatric disorders. Disclosures:No relevant conflicts of interest to declare.

Vegetarian Diets in Children and Adolescents

1. Meredith Renda, MD* 2. Philip Fischer, MD* 1. *Department of Pediatrics, Mayo Clinic, Rochester, Minn Vegetarianism is becoming more common among adults, with 1 in 40 adults currently choosing a vegetarian diet. Consequently, more children are raised as vegetarians. Vegetarianism is adopted for various reasons, including moral, religious, and health. Numerous studies have shown significant health benefits for individuals following this type of diet. Pediatricians should be well informed about vegetarianism and its role in our pediatric population. A first-time mother and her 2-month-old boy present to the clinic for a health supervision visit. The mother is breastfeeding, and her baby is growing appropriately. At the end of the visit, the mother mentions that she is a vegetarian and that she would like to raise her son in the same way. She would like to know what she should be doing as a breastfeeding mother and how she can make sure that her son has the appropriate nutrition in the future . The physician should begin by taking a dietary history from the mother to determine what type of vegetarianism she practices. He or she should explain to the mother that her infant's nutrition is based on her own dietary intake for as long as she continues to breastfeed. The pediatrician should counsel the mother on the importance of diet variety. If the mother is vegan, the pediatrician must take time to ensure that she is getting enough vitamin B12 and calcium in her diet. When she is ready to wean her infant, she should continue to focus on dietary variety. The mother should be cautioned that adult vegetarian diets that are high in bulk and low in calories are not always appropriate for the growing and developing child. Finally, the pediatrician should ensure that the mother has the appropriate resources to guide her in finding the best foods for her child's nutritional needs. …

Another Reason for Maternal Folic Acid Supplementation

Maternal folic acid deficiency is known to be associated with neural tube defects in infants, but the possibility of a relation between folic acid

Folate Synthesis and Metabolism in Plants and Prospects For Biofortification

Folates are essential cofactors for one‐carbon transfer reactions in most living organisms and are required for the biosynthesis of nucleic acids, amino acids, and pantothenate. Unlike plants and microorganisms, humans cannot synthesize folates de novo and must acquire them from the diet, primarily from plant foods. However, lack of folates is the most common vitamin deficiency in the world and has serious health consequences, including increased risk of neural tube defects in infants, cancers, and vascular diseases. Consequently, there is much interest in engineering plants with enhanced folate content (biofortification). In this review, we outline progress in defining the plant folate synthesis pathway and its unique compartmentation and point out sectors of folate metabolism that have yet to be elucidated, including transport and catabolism. We also consider possible strategies to enhance plant folate synthesis and accumulation by metabolic engineering.

Folic Acid Supplementation and Twin Pregnancy in Patients with Sickle Cell Disease.

Patients with sickle cell disease (SCD) usually take 1mg of folic acid daily. The rationale for this approach is to maintain effective erythropoiesis with a stable hemoglobin level. Other potential advantages of folate therapy in patients with SCD include the prevention of hyperhomocysteinemia that may predispose to thrombotic events, which, in turn, may lead to painful episodes. Moreover, folate supplementation during pregnancy is known to prevent neural tube defects in infants. The major disadvantage of folate supplementation in patients with SCD is that it may mask vitamin B12 deficiency. Another controversial effect of folic acid supplementation pertains to its potential effect on the number of twins coming to term. We reviewed our database on patients with SCD to determine the effect, if any, of folic acid supplementation on twin pregnancies. The data were collected prospectively since 1981. All patients routinely took 1.0 mg of folic acid orally on a daily basis. Random testing of the level of folic acid in the steady state in women with SCD including those who became pregnant showed increased levels to > 20ng/ml (Normal range: 3.0–18.0 ng/ml) in most patients. Pregnant patients also took additional perinatal vitamins that also contained folic acid. We selected those pregnant patients in whom the outcome of pregnancy was either a liveborn or stillborn at or after 20 weeks' gestation. We found that 46 patients with SCD became pregnant 60 times between 1981 and 2002 and who met the defined criteria mentioned above. The average maternal age at delivery was 26 years. Fifty-six pregnancies (93%) ended in liveborn and the remaining four (7%) in intrauterine fetal death. Five pregnancies (8.3%) resulted in the delivery of twins. This is a significantly higher rate of multiple births compared to other pregnant women. The reported rate of multiple births is between 0.34 and 1.1% both in Black and Caucasian women respectively. All twin births were dizygotic in nature. Patients with SCD take higher amounts of folic acid on a regular basis for a longer period of time before and after pregnancy than other pregnant women. This may explain why twin pregnancies are higher in these patients. The reason why folate therapy is associated with twinning is unknown at the present. Further studies may clarify the pathogenetic pathway of this phenomenon.