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The United States implemented mandatory fortification of cereal grains with folic acid in 1998 to prevent neural tube defects (NTDs) during pregnancy. The health benefits of folate (vitamin B9) are well documented; however, there are potential risks of exceeding the upper tolerable limit, particularly in vulnerable populations. We conducted a popul...
Context in source publication
Context 1
... average prevalence of NTDs per 10,000 births in countries that do not fortify any cereal grains with folic acid was 13.32 (SD: 5.50, n = 116 countries), and the average prevalence of NTDs in countries with at least one cereal grain fortified with folic acid was 13.30 (SD: 6.13, n = 70). Stratification of the data based on which cereal grain was fortified with folic acid indicated no statistically significant differences in the prevalence of NTDs comparing wheat, maize, and rice fortification versus no fortification, albeit there was a trend for reduced NTDs with folic acid fortification of maize (p = 0.065) ( Table 2, Figures 1-4). There was a very weak correlation between NTD prevalence and the level of folic acid fortification irrespective of the cereal grain fortified: wheat (Figure 1), maize (Figure 2), and rice ( Figure 3). ...Similar publications
Optimal micronutrient status is critical to the health of women, particularly during their reproductive years. A woman’s health and nutritional status during the preconception stage thus has significant implications for pregnancy outcomes and her offspring’s health later in life. In this review, we evaluated micronutrient intakes and status (iron,...
Citations
... It has been demonstrated that folates and FA can reduce the risk of neural tube defects. As a result, numerous countries have established mandatory folic acid fortification policies to increase the consumption of folic acid among women of childbearing age [12]. Chile has implemented a mandatory fortification policy since 2000, which is considered a safe, cost-effective, and sustainable intervention. ...
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Many women with PCOS have been found to have an unbalanced diet and deficiencies in essential nutrients. This study aimed to assess the levels of folate and vitamin B12 (B12) and their relationship with metabolic factors in women with PCOS. Anthropometric, clinical, and genetic analyses were conducted to evaluate markers related to one-carbon metabolism in women with PCOS and in a control group. The PCOS group had a higher BMI and HOMA-IR (1.7 vs. 3.1; p < 0.0001). HDL cholesterol levels were 23% lower and triglyceride levels were 74% higher in women with PCOS. Although there were no significant differences in folate and B12 levels between the PCOS and control groups, over 60% of women with PCOS had low B12 levels (<300 pg/mL) and high homocysteine levels. In addition, the MTHFR A1298C and C677T polymorphisms were not associated with PCOS. Moreover, erythrocyte folate levels were positively correlated with fasting glucose, triglycerides, and free androgen index, and negatively correlated with SHBG and LH levels. These results suggest that B vitamins may be associated with the metabolic phenotype in PCOS. This study emphasizes the potential link between folate, vitamin B12, and metabolic and hormonal outcomes in women with PCOS.
... Although there is no conclusive evidence for any overall benefit of FA supplementation beyond 12 weeks gestation (31 trials involving 17,771 women) (De-Regil et al., 2015), many women continue to take FA supplements throughout their whole pregnancy, typically at amounts up to 800 µg/day or higher (Shand et al., 2016). In addition, as NTDs occur in the first month of pregnancy and many pregnancies are unplanned, more than 80 countries, including Australia, Canada and the USA, have mandated fortification of staple foods with FA, further increasing FA intakes of pregnant women (Murphy & Westmark, 2020). ...
Pregnant women are advised to take folic acid (FA) supplements before conception and during the first trimester of pregnancy. Many women continue FA supplementation throughout pregnancy, and concerns have been raised about associations between excessive FA intake and adverse maternal and child health outcomes. Unmetabolized folic acid (UMFA) is found in serum after high FA intakes and is proposed as a biomarker for excessive FA intake. We aimed to determine if removing FA from prenatal micronutrient supplements after 12 weeks of pregnancy reduces serum UMFA concentrations at 36 weeks gestation. In this double‐blind, randomized controlled trial conducted in South Australia, 103 women with a singleton pregnancy were randomly assigned at 12–16 weeks gestation to take a micronutrient supplement containing no FA or 800 µg/day FA from enrollment until 36 weeks gestation. Ninety women (0 µg/day FA n = 46; 800 µg/day FA n = 44) completed the study. Mean, UMFA concentration was lower in the women randomized to the 0 µg/day group compared to the 800 µg/day FA group, 0.6 ± 0.7 and 1.4 ± 2.7 nmol/L, respectively. The adjusted mean difference (95% CI) in UMFA between the groups was [‐0.85 (−1.62, −0.08) nmol/L, p = 0.03]. Maternal serum and red blood cell folate concentrations were lower in the 0 µg/day FA group than in the 800 µg/day group (median 23.2 vs. 49.3 and 1335 vs. 1914 nmol/L, respectively; p < 0.001). Removing FA at 12–16 weeks gestation from prenatal micronutrient supplements reduced the concentration of UMFA at 36 weeks gestation.
... According to some studies, there is 60-100% reduction in the risk of NTD pregnancy after folic acid intervention among pregnant women with prior NTD-affected pregnancies. 12 Observational studies of folic acid efficacy in preventing NTD in pregnant women without a prior NTD-affected pregnancy showed a 0-75% reduction in risk. 12 In the present study, 16 (53.3%) ...
... 12 Observational studies of folic acid efficacy in preventing NTD in pregnant women without a prior NTD-affected pregnancy showed a 0-75% reduction in risk. 12 In the present study, 16 (53.3%) mothers with an NTD child have not at all consumed folic acid during their entire pregnancy, and the others took folic acid during the first two trimesters but irregularly. ...
Objective
To estimate the prevalence of neural tube defects among all birth outcomes in Odisha during 2016–2022. Additionally, to estimate the identification rate of neural tube defects during Pradhan Mantri Surakshit Matritva Abhiyan sessions.
Design
A population-based cross-sectional study with a household survey for neural tube defects using pictorial card as well as a hospital-based study for antenatal ultrasonography data.
Setting
The sample population was selected through multistage random sampling. In the first stage, one district from each zone was selected randomly. In the second stage, using simple random sampling, one community health centre and one urban primary health centre were selected from each district. In the third stage, the population from a block and ward were picked from the selected rural and urban settings, respectively.
Participants
All married women in the reproductive age group (18–49 years) residing in these cluster villages in the selected districts were enrolled.
Results
The study surveyed 49 215 women and recorded 50 196 birth outcomes, including 49 174 live births, 890 stillbirths and 132 medical terminations of pregnancy. A total of 30 neural tube defect cases were detected. The overall prevalence rate of neural tube defect was 0.59 per 1000 birth outcomes. Spina bifida was the most prevalent neural tube defect with the prevalence of, followed by anencephaly and encephalocele. Despite 26 860 mothers receiving antenatal ultrasonography Pradhan Mantri Surakshit Matritva Abhiyan session, data on neural tube defects and other birth defects detected through these scans is unavailable.
Conclusion
This study found a low prevalence of neural tube defect in Odisha, which is far lower compared with the older studies from India. There is an urgent need to strengthen the quality of antenatal care services provided under Pradhan Mantri Surakshit Matritva Abhiyan through better training regarding anomaly scans and better data keeping at public healthcare facilities.
Trial registration number
CTRI/2021/06/034487.
... More importantly, folic acid insufficiency has been suggested as a risk factor for oral clefts. Consumption of folic acid before and during early pregnancy reduces the chance of neural tube defects and oral clefts [11][12][13][14][15]. According to the latest study regarding the prevalence of CL/P among American mothers from 2010 to 2014, the total prevalence rate per 10,000 births reported to be 10.25 with the highest prevalence among non-Hispanic American Indians and non-Hispanic Alaska Natives (AIAN) [16]. ...
Backgrounds
Cleft lip with or without cleft palate (CL/P) is the most common congenital craniofacial anomaly, including non-syndromic cleft lip with or without cleft palate and cleft palate only. Failure in the fusion of median and lateral nasal processes, the maxillary prominence, and soft tissues around the oral cavity can cause CL/P. Previously, the prevalence has been estimated to be 1 among every 1000 births in 2014 among American neonates and no other reports have been available since. Thus, this study aimed to calculate the prevalence and trend of isolated CL/P among American live births from 2016 to 2021 with its associated risk factors.
Methods and materials
In this cross-sectional population-based retrospective study, we used live birth data provided by the National Center for Health Statistics (NCHS) from the Center for Disease Control and Prevention (CDC). We calculated the prevalence per 10,000 live births of isolated (non-syndromic) CL/P from 2016 to 2021. To examine risk factors for developing isolated CL/P, we used logistic regression modelling.
Results
The total prevalence per 10,000 births from 2016 to 2021 was 4.88 (4.79–4.97), for both sexes, and 5.96 (5.82–6.10) for males, and 3.75 (3.64–3.87) for females. The prevalence did not show any consistent linear decreasing or increasing pattern. We found significant association between increased odds of developing isolated CL/P among cases with 20 to 24 year-old mothers (OR = 1.07, 1.01–1.13, p = 0.013), mothers who smoked 11 to 20 cigarettes per day (OR = 1.46, 1.33–1.60, p < 0.001), mothers with extreme obesity (OR = 1.32, 1.21–1.43, p < 0.001), mothers with grade II obesity (OR = 1.32, 1.23–1.42, p < 0.001), mothers with pre-pregnancy hypertension (OR = 1.17, 1.04–1.31, p = 0.009), mothers with pre-pregnancy diabetes mellitus (OR = 1.96, 1.71–2.25, p < 0.001), and mothers who used assisted reproductive technology (OR = 1.40, 1.18–1.66, p < 0.001).
Conclusions
Our findings suggest a minuscule increase, albeit insignificant, in the trend of CL/P prevalence from 2016 to 2021. Developing CL/P had greater odds among mothers with pre-pregnancy diabetes, smoking, obesity, and pre-pregnancy hypertension mothers along with mothers who used assisted reproductive technology. Isolated CL/P had the highest prevalence in non-Hispanic Whites, American Indian or Alaskan Native and Native Hawaiian and Other Pacific Islanders.
... Although adequate folate intake is critically essential for human health and the prevention of neural tube defects (NTDs), limited evidence in animal [24][25][26] and population studies have associated elevated FA intake with the increased risk for cancer [27,28], cardiometabolic diseases [17,29,30], and neurocognitive endpoints [31][32][33][34]. This suggestive evidence raises questions about potential unanticipated metabolomic effects associated with moderate-to-high FA intake and UMFA [29,35,36]. However, the current evidence is incomplete as dose-response data are lacking and the biological pathways and potential metabolomic effects of FA supplementation remain unknown [32][33][34][37][38][39]. ...
... Previous studies have shown that administering folic acid to expectant mothers significantly reduces the likelihood of their newborns developing neural tube defects (NTDs) (7). Consequently, some nations have implemented compulsory folic acid fortification programs (8). However, several Western European countries have yet to enforce mandatory folic acid fortification, partly due to concerns about potential adverse effects on cancer incidence (9). ...
... However, several Western European countries have yet to enforce mandatory folic acid fortification, partly due to concerns about potential adverse effects on cancer incidence (9). Furthermore, a recent data analysis examining the correlation between national folic acid fortification and the risk of NTDs found no significant association between folic acid fortification and a decreased incidence of NTDs in the population (8). Therefore, the potential negative consequences of folic acid supplementation should be a focal point of attention. ...
Previous researchers have tried to explore the association between folate/folic acid intake and dementia incidence, but the results remain controversial. We evaluated the associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure. A total of 466,224 UK Biobank participants were investigated. Cox proportional hazards models were used to assess the associations between folate/folic acid supplementation status and the risk of Alzheimer's disease (AD) and vascular dementia (VD). Multivariable linear regression models were employed to evaluate the association between folate/folic acid supplementation status and brain structure. In the final model, folate/folic acid supplementation alone was significantly associated with a higher risk of AD (hazard ratio [HR] =1.34, 95% confidence interval [CI] =1.06 to 1.69, p=0.015) and VD (HR=1.61, 95% CI=1.21 to 2.13, p=0.001). Folate/folic acid supplementation alone was associated with a reduction in the hippocampus (β= -95.25 mm3, 95% CI= -165.31 to -25.19 mm3, p=0.014) and amygdala (β= -51.85 mm3, 95% CI= -88.02 to -15.68 mm3, p=0.012). The risk of AD and VD, as well as brain structure, in the group with combined folate/folic acid supplementation and other B vitamins did not show a statistically significant difference compared to the reference group (all p>0.05). Folate/folic acid supplementation alone is significantly associated with a higher risk of AD and VD, as well as adverse alterations in brain structure. However, when combined with other B vitamins, these detrimental effects can be counteracted.
... Therefore, to prevent NTDs, folic acid should be taken starting from at least one month before conception until the end of the first trimester to ensure that maternal folate levels are sufficient in the early stages of pregnancy when neural tube closure occurs [24,25]. It is difficult to get enough folate from diet alone [26]; around 80 countries, including the USA, Canada, Chile, and South Africa, have mandated the fortification of staple food products, such as corn and wheat, with folic acid to increase folate levels in the population and decrease adverse health outcomes [27,28]. In 1998, in the USA, the FDA required that all enriched grain products be fortified with folic acid [29]. ...
Background
Maternal folic acid supplementation is protective against the development of neural tube defects (NTDs) in babies. However, recent public-facing communications have raised concerns about a causal relationship between folic acid supplementation, particularly after the first trimester, and ankyloglossia (tongue-tie) in infants. Non-evidence-based communications are potentially harmful because they could adversely affect adherence to folic acid supplementation, increasing NTD occurrence. This study aimed to review evidence on the relationships between maternal folic acid supplementation during preconception and/or pregnancy and the risk of ankyloglossia in infants.
Methods
We searched the databases MEDLINE, EMBASE, Cochrane CENTRAL, and Scopus. We searched for observational, and interventional studies, and systematic reviews investigating the effect of maternal folic acid supplementation during preconception or pregnancy on the occurrence of ankyloglossia in offspring. The search was registered on PROSPERO on 01/12/2022, ID: CRD42022375862.
Results
The database searches yielded 93 articles. After removing duplicates and screening titles and abstracts, 26 remained. One article was judged relevant for inclusion in analyses; a case-control study that directly mentions the relationship between folic acid supplementation and ankyloglossia . This study r eported that regular intake of folic acid supplements was higher in women with infants with ankyloglossia. However, this study has limitations regarding design, selection bias, and confounding, calling the findings into question.
Conclusions
Insufficient evidence exists for a relationship between folic acid supplementation and ankyloglossia. Currently, the benefits of folic acid supplementation far outweigh the risks. This must be clearly communicated to patients by their clinicians during preconception and antenatal care.
... Additionally, it is effective in treating FXS phenotypes, including hyperactivity, anxiety, antisocialism, and cognitive deficits, in Fmr1 K O mice (Liu et al., 2011). A personalized medicine approach will be required to implement micronutrient-mediated therapy for ASDs, particularly considering the contradictory evidence regarding the efficacy of population level folic acid supplementation and neural tube defects (Murphy and Westmark, 2020). ...
Altering the diet to treat disease dates to c. 400 BC when starvation was used to reduce seizures in persons with epilepsy. The current diversity of symptomology and mechanisms underlying autism spectrum disorders (ASDs) and a corresponding lack of disorder-specific effective treatments prompts an evaluation of diet as a therapeutic approach to improve symptoms of ASDs. In this review article, we summarize the main findings of nutritional studies in ASDs, with an emphasis on the most common monogenic cause of autism, Fragile X Syndrome (FXS), and the most studied dietary intervention, the ketogenic diet as well as other dietary interventions. We also discuss the gut microbiota in relation to pre- and probiotic therapies and provide insight into future directions that could aid in understanding the mechanism(s) underlying dietary efficacy.
... The USA was the first nation to implement mandatory folic acid fortification for the prevention of NTDs, which has significantly reduced their incidence [14]. Currently, more than 80 other countries have adopted the US policy of fortifying cereal grains with folic acid [14]. ...
... The USA was the first nation to implement mandatory folic acid fortification for the prevention of NTDs, which has significantly reduced their incidence [14]. Currently, more than 80 other countries have adopted the US policy of fortifying cereal grains with folic acid [14]. Fortified products include staple items such as foods like bread, four, rice, pasta, and breakfast cereals [15]. ...
Inadequate folate intake during pregnancy is the leading cause of the development of neural tube defects (NTDs) in newborns. For this reason, mandatory fortification of folic acid, a synthetic, easily bioavailable form, in processed cereals and cereal products has been implemented in the US since 1 January 1998 to reduce the risk of NTD in newborn children. This report aimed to review the literature related to the impact of mandated folic acid fortification on the intended and unintended benefits to health. Potential adverse effects were also discussed. We searched Pubmed, Google Scholar, Embase, SCOPUS, and Cochrane databases for reports. About 60 reports published between January 1998 and December 2022 were reviewed, summarized, and served as background for this review. The intended benefit was decreased prevalence of NTDs, while unintended benefits were reduction in anemia, blood serum homocysteine, and the risk of developing cardiovascular diseases. Potential issues with folic acid fortification are the presence of unmetabolized folic acid in circulation, increased risk of cancer, and the masking of vitamin B-12 deficiency. From a health perspective, it is important to monitor the impact of folic acid fortification periodically.
... In Australia, folic acid (FA) supplementation, with a daily dose of 400 µg for at least one month prior to and during the first trimester of pregnancy, has been part of clinical guidelines for over 20 years and was proven to reduce the incidence of neural tube defects [3,4]. To ensure that all women of reproductive age have sufficient folate levels, including those who may conceive unintentionally and are unlikely to supplement, over 80 governments across the world implemented mandatory FA food fortification programs [5]. The Australian government implemented a FA fortification mandate for bread-making flour in 2009 [6]. ...
... A recent systematic review of women taking defects [3,4]. To ensure that all women of reproductive age have sufficient folate levels, including those who may conceive unintentionally and are unlikely to supplement, over 80 governments across the world implemented mandatory FA food fortification programs [5]. The Australian government implemented a FA fortification mandate for bread-making flour in 2009 [6]. ...
Folic acid (FA) food fortification in Australia has resulted in a higher-than-expected intake of FA during pregnancy. High FA intake is associated with increased insulin resistance and gestational diabetes. We aimed to establish whether maternal one-carbon metabolism and hormones that regulate glucose homeostasis change in healthy pregnancies post-FA food fortification. Circulating folate, B12, homocysteine, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early pregnancy maternal blood in women with uncomplicated pregnancies prior to (SCOPE: N = 604) and post (STOP: N = 711)-FA food fortification. FA food fortification resulted in 63% higher maternal folate. STOP women had lower hPL (33%) and GH2 (43%) after 10 weeks of gestation, but they had higher PRL (29%) and hPL (28%) after 16 weeks. FA supplementation during pregnancy increased maternal folate and reduced homocysteine but only in the SCOPE group, and it was associated with 54% higher PRL in SCOPE but 28% lower PRL in STOP. FA food fortification increased maternal folate status, but supplements no longer had an effect, thereby calling into question their utility. An altered secretion of hormones that regulate glucose homeostasis in pregnancy could place women post-fortification at an increased risk of insulin resistance and gestational diabetes, particularly for older women and those with obesity.
