Folic Acid

Folic acid, also known as folate or vitamin B9, is one of the 13 essential vitamins that are required for cell growth and function. It is not produced by the body, and therefore must be obtained either from diet or supplementation. Folate occurs naturally in foods such as leafy green vegetables, black-eyed peas, lentils, rice, egg yolk, asparagus, and citrus fruit. Folic acid is a synthetic vitamin that is added to select foods, taken as a stand-alone supplement, or included in a multivitamin. Prenatal and intrapartum folic acid supplementation is widely accepted as standard of care to prevent neural tube defects and structural malformations.4 Less well known is the impact of genetic polymorphisms (generic variations) that affect metabolism of folate and folic acid and its subsequent impact on pregnancy outcomes.

Both folate and folic acid are metabolically inactive and must be metabolically reduced to L-5-methyltetrahydrofolate (5MTHF) to be able to contribute to cellular metabolism.5 MTHFR genetic polymorphisms reduce metabolism of folate and folic acid.6 Two meta-analyses examining the MTHFR gene polymorphism, C677T, and risk for neural tube defects found a significant association, implying that women with a C677T polymorphism are at higher risk for delivering an infant with neural tube defects.7,8 In the United States, evidence suggests that up to 43% of American Indians and 34% of Americans of European descent have the most common MTHFR polymorphism (C677T). Asian populations were found to have up to 20% prevalence of the C677T polymorphism.8

The current folic acid recommendation is 0.4 to 0.8 mg/d for all women of childbearing age.9 With respect to estimates of the population carrying the MTHFR polymorphism, it may be beneficial to supplement with the bioavailable form of folate, L-5-MTHF.8 This form of folic acid does not require the metabolic activation that can be impaired with a genetic polymorphism. L-5-MTHF has been tested in healthy women and has been shown to be safe and at least as effective as folic acid.5,10 Individuals with known MTHFR mutations and a history of offspring with neural tube defects are clearly targeted for supplementation with the metabolically reduced, more bioavailable L-5-MTHF. However, recommending L-5-MTHF to all women of childbearing age may protect those not yet diagnosed with methylation polymorphisms.

Recommendation: 5MTHF, 400 µg/d, as tolerated for all women of childbearing age may be included in a routine prenatal vitamin or consumed as a stand-alone supplement.

Iodine

Iodine is a micronutrient that is necessary for thyroid function. When a woman becomes pregnant, thyroid function increases dramatically to meet increasing metabolic demands.11 Lack of iodine in pregnancy has devastating, permanent consequences, and robust evidence links iodine insufficiency to multiple negative outcomes in pregnancy, including lower child IQ, child neural abnormalities, miscarriage, infant mortality, congenital iodine deficiency syndrome, and, most recently, autism.11,12 Foundational fetal neurologic formations initiated in the first trimester depend on thyroid hormones to develop correctly. The iodine recommendation for nonpregnant adult women is 150 µg/d; once a woman becomes pregnant, that recommendation increases to 220 to 250 µg, and increases to 290 µg/d while breastfeeding.13

The United States population is classified as having “more than adequate” iodine levels based on population urine iodine concentration (UIC) collected in 2009 and 2010; more recent evaluation of UICs in US women found a median UIC of 144 µg/L, which is lower than the recommended 150 µg/L.14 Black women had the lowest UIC, at 131 µg/L; the median UIC for pregnant women even lower at 129 µg/L. A separate dataset found similarly low UICs: the median UIC for all adult women was 134 µg/L, the median UIC for women of childbearing age was 124 µg/L, and the median UIC for black women was 131 µg/L. These results are alarming, because the UIC of the US population has been considered more than adequate, and concerns of iodine deficiency are dismissed as a problem of other world regions. However, these results demonstrate that iodine deficiency is a condition that all providers need to address. Over the past several decades, the iodine status of the US population has declined from a median UIC of 320 μg/L to 145 μg/L (1 μg/L = 0.079 μmol/L), representing a 50% decrease, according to the National Health and Nutrition Examination Survey (NHANES I; 1971–1974) and NHANES III (1988–1994), respectively.14

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One of the challenges in assessing and treating iodine deficiency is that there is no reliable clinical marker of individual iodine levels. Although UIC is often used as a marker for population iodine levels, it is less helpful as an individual indicator. Clinicians evaluating iodine levels in individual patients need to consider indirect indicators of iodine levels.

Providers should inquire and assess dietary intake of iodine. Although the United States implemented iodized salt in 1942, many salts lack iodine. Estimates suggest that the US population obtains 60% of its iodine from dairy sources, both from feed given to dairy cows, and from iodine-containing processing methods, suggesting a reduced iodine intake in dairy-free diets.14 Approximately 70% of salt consumed in the United States comes from processed and restaurant foods that generally do not use iodized salt.14 The Institute of Medicine’s recommendation to reduce sodium intake for cardiovascular health many also contribute to low iodine intake.15