[Folate, Choline, and Vitamin B12 Supplementation for Pre-Conceptional and Pregnant Women]. / Folat-, Cholin-, und Vitamin-B12-Supplementierung für präkonzeptionelle und schwangere Frauen.

Folate, Choline, and Vitamin B12 Supplementation for Pre-Conceptional and Pregnant Women Abstract. Inadequate maternal folate status is associated with higher risk of neural tube defects. The threshold for a good supply of folate (e.g., folate concentration in erythrocytes) is > 906nmol/L for all women who may become pregnant. This quite high folate concentration should already be reached before the onset of pregnancy, which can hardly be achieved with food. Supplementation with folate or folic acid is therefore strongly recommended for all women planning pregnancy (four to eight weeks before the start of pregnancy until the end of the first trimester). Folate supplementation can significantly reduce the risk of neural tube defects at the population level (approximately 50%), but it cannot prevent all cases. Recent studies show that low maternal choline and vitamin B12 intake during pregnancy is also associated with higher risk of neural tube defects. The role of choline in fetal brain development is biologically plausible based on its function as a source of methyl groups, acetylcholine, and cell membrane phospholipids and is not completely interchangeable with folate. Data on the association between maternal choline intake during preconception and the first trimester and fetal brain development suggest a causal relationship. The intake recommendation for choline is 480mg/day for pregnant women and 550mg/day for lactating women. Choline intake (mainly from animal-based diets) averages about 300mg/day and is thus insufficient for optimal supply during pregnancy. To date, no specific recommendations exist for choline supplementation before and during pregnancy. In Europe, prevention approaches at the population level are generally poorly followed. Therefore, individual counseling of young women planning pregnancy is more relevant than ever.

Folate supplementation for prevention of congenital heart defects and low birth weight: an update.

Women planning a pregnancy and pregnant women in the first trimester are recommended to use folate-containing supplements in order to prevent neural tube defects. The prevention of many cases of neural tube defects with folic acid is evident from meta-analysis, randomized controlled trials (RCTs), observational studies in humans and experimental evidence in animals. However, folate supplementation in pregnant women or a higher maternal folate status has been shown to be protective against other adverse birth outcomes such as congenital heart defects, low birth weight, and preterm birth. Additionally, infants and children with congenital heart defects often show disorders in folate metabolism (low folate, higher homocysteine, or low vitamin B12). Maternal genotype for several folate metabolizing genes has shown associations with the risk of having a child with congenital heart defect. There is some evidence that folate supplementation could have differential effects on sub-types of congenital heart defects, but it is not clear whether the prevention time window is the same as for neural tube defects. Some studies proposed a high dose of folic acid (in mg/d) to prevent congenital heart defects in women with a high global risk (such as those with diabetes or obesity). There are currently no RCTs to support that doses of folic acid in mg range are more effective than the currently recommended 400-800 µg/d taken at least 2-3 months before conception until the end of the first trimester.

Preventable spina bifida and anencephaly in Europe.

BACKGROUND: Promotion of voluntary folic acid supplement use among women of reproductive age has been proven to be ineffective in lowering the risk of neural tube defects in Europe. METHODS: Using surveillance data from all births covered by the full member countries of the European Surveillance of Congenital Anomalies (EUROCAT), we estimated the total prevalence of spina bifida and anencephaly per 10,000 births between 2000 and 2010. We also estimated additional lifetime direct medical costs among individuals with spina bifida, compared with those without, in Germany for the year 2009. RESULTS: During the study period, there were 7478 documented cases of spina bifida and anencephaly among the 9,161,189 births, with an estimated average combined prevalence of 8.16 per 10,000 births (95% confidence interval, 7.98 - 8.35). For the 241 spina bifida-affected live births in 2009 in Germany, the estimated additional lifetime direct medical costs compared with non-spina bifida affected births were €65.5 million. Assuming a 50% reduction in the prevalence if folic acid has been provided to all women before pregnancy, 293 spina bifida cases could have been prevented in Germany in 2009. The estimated lifetime direct medical cost saving for the live births in 2009 was €32.9 million assuming a 50% reduction, or €26.1 million assuming a 40% risk reduction. CONCLUSION: Europe has an epidemic of spina bifida and anencephaly compared with countries with mandatory folic acid fortification policy. Primary prevention through mandatory folic acid fortification would considerably reduce the number of affected pregnancies, and associated additional costs.

Is 5-methyltetrahydrofolate an alternative to folic acid for the prevention of neural tube defects?

Women have higher requirements for folate during pregnancy. An optimal folate status must be achieved before conception and in the first trimester when the neural tube closes. Low maternal folate status is causally related to neural tube defects (NTDs). Many NTDs can be prevented by increasing maternal folate intake in the preconceptional period. Dietary folate is protective, but recommending increasing folate intake is ineffective on a population level particularly during periods of high demands. This is because the recommendations are often not followed or because the bioavailability of food folate is variable. Supplemental folate [folic acid (FA) or 5-methyltetrahydrofolate (5-methylTHF)] can effectively increase folate concentrations to the level that is considered to be protective. FA is a synthetic compound that has no biological functions unless it is reduced to dihydrofolate and tetrahydrofolate. Unmetabolized FA appears in the circulation at doses of >200 µg. Individuals show wide variations in their ability to reduce FA. Carriers of certain polymorphisms in genes related to folate metabolism or absorption can better benefit from 5-methylTHF instead of FA. 5-MethylTHF [also known as (6S)-5-methylTHF] is the predominant natural form that is readily available for transport and metabolism. In contrast to FA, 5-methylTHF has no tolerable upper intake level and does not mask vitamin B12 deficiency. Supplementation of the natural form, 5-methylTHF, is a better alternative to supplementation of FA, especially in countries not applying a fortification program. Supplemental 5-methylTHF can effectively improve folate biomarkers in young women in early pregnancy in order to prevent NTDs.

Adding folate to the contraceptive pill: a new concept for the prevention of neural tube defects.

Although it is proven for a long time that folic acid supplementation in the periconceptional period can prevent neural tube defects (NTDs) effectively, all measures taken so far including food fortification and awareness campaigns so far had only limited success. Since more than 50% of the pregnant women in Europe get pregnant after they have used oral contraceptives (OCs) before, OCs are an ideal vehicle to increase not only the awareness for periconceptional folate application, but they can also help to bridge the gap between the recognition of a pregnancy and closure of the neural tube which is before day 26. In order to reach a truly protective folate level at the critical time period during pregnancy, now OCs are available which contain metafolin. The availability of this innovative type of OC will significantly reduce the number of NTDs.

Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part II--vitamin D, vitamin A, iron, zinc, iodine, essential fatty acids.

Part II of this review considers additional micronutrients. Vitamin D is a fat soluble vitamin found in foods of animal origins (fatty fish, liver oil) or fortified products (milk, cheese). Vitamin D deficiency is common in African-American women living in northern latitudes. Vitamin D supplementation may be needed to reach desired 25-(OH)D3 concentrations of >50 nmol/L. In foods of animal origin, preformed Vitamin A is present; in plants (fruits and vegetables) vitamin A precursors (ß-carotenoids) are present. Vitamin A supplementation is usually not warranted, and in developing countries should not exceed 3000 µg (10,000 IU)/day. Iron in the form of haem-iron is found in meat, fish and poultry; non-haem (inorganic) iron is found in vegetables, fruits and grains. Iron supplementation may be necessary in the third trimester, earlier in pregnancy or in non-pregnant states if serum ferritin is <20 µg/L or haemoglobin <10.9 g/dL. Zinc is available in red meat, seafood including oysters and unpolished grains; supplementation is not necessary. To assure adequate iodine, food is fortified worldwide with iodated salt. If urinary iodine levels are low, supplementation is needed. Essential fatty acids requirements can be met by one to two portions of fish per week.

Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part I--Folate, Vitamin B12, Vitamin B6.

This two-part review highlights micronutrients for which either public health policy has been established or for which new evidence provides guidance as to recommended intakes during pregnancy. One pivotal micronutrient is folate, the generic name for different forms of a water-soluble vitamin essential for the synthesis of thymidylate and purines and, hence, DNA. For non-pregnant adult women the recommended intake is 400 µg/day dietary folate equivalent. For women capable of becoming pregnant an additional 400 µg/day of synthetic folic acid from supplements or fortified foods is recommended to reduce the risk of neural tube defects (NTD). The average amount of folic acid received through food fortification (grains) in the US is only 128 µg/day, emphasising the need for the supplemental vitamin for women of reproductive age. Vitamin B12 (cobalamin) is a cofactor required for enzyme reactions, including generation of methionine and tetrahydrofolate. B12 is found almost exclusively in foods of animal origin (meats, dairy products); therefore, vegetarians are at greatest risk for dietary vitamin B12 deficiency and should be supplemented. Vitamin B6 is required for many reactions, primarily in amino acid metabolism. Meat, fish and poultry are good dietary sources. Supplementation beyond routine prenatal vitamins is not recommended.

The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations.

This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines for health-care providers supported by the World Association of Perinatal Medicine, the Early Nutrition Academy, and the Child Health Foundation are provided. The fetus and neonate should receive LC-PUFA in amounts sufficient to support optimal visual and cognitive development. Moreover, the consumption of oils rich in n-3 LC-PUFA during pregnancy reduces the risk for early premature birth. Pregnant and lactating women should aim to achieve an average daily intake of at least 200 mg DHA. For healthy term infants, we recommend and fully endorse breastfeeding, which supplies preformed LC-PUFA, as the preferred method of feeding. When breastfeeding is not possible, we recommend use of an infant formula providing DHA at levels between 0.2 and 0.5 weight percent of total fat, and with the minimum amount of AA equivalent to the contents of DHA. Dietary LC-PUFA supply should continue after the first six months of life, but currently there is not sufficient information for quantitative recommendations.

Role of omega 3-fatty acids and multivitamins in gestation.

There is a rising interest in a balanced and varied women's diet not only preconceptionally but also during pregnancy and in the breastfeeding period in order to reduce fetal, neonatal, and maternal risks. A decreased intake of omega 3-fatty acids (FA) or deficiencies of micronutrients are a global health problem, not only in developing countries, where micronutrient-rich food and fortified aliments are often not available, and also in the industrialized world. In contrast to data about the daily preconceptionally intake of folate acid that has been shown to reduce substantially the occurrence and recurrence of neural tube defects (NTD), the benefit of other micronutrients is less determinant. Deficiencies of omega 3-FA may be a contributing factor for severe complications in pregnancy and postpartum. A meta-analysis for the role of omega 3-FA in preeclampsia and maternal postpartum depression is less consistent, some meta-view's results differ substantially or are even contradictory to large observational studies. Further well-designed studies are warranted. A personal interview and counseling concerning the daily diet should be integrated in the preconceptional and in the antenatal care and an individual supplementation should be offered, if indicated.

Psychological management of pregnancy-related breast cancer.

The comprehensive care of a pregnant patient in whom breast cancer is diagnosed presents a challenge to the biomedical and psychological competence of the medical team. Illustrated by a case presentation the different phases of psychological care are delineated and discussed: the confrontation with the diagnosis of a life-threatening disease in a situation in which the beginning of a future life is celebrated. Special attention is given to breaking bad news, the establishment of a stable and trustful physician-patient relationship, communicating risk and to the extremely difficult decision-making process regarding termination or continuation of pregnancy (shared decision-making). The delicate balance between oncological care for the mother with a high-risk disease and a high-risk pregnancy and neonatal care for the foetus is outlined, including regular talks about emotions and concerns.