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Vitamins, minerals and trace elements
Vitamins and minerals are organic foods found only in plants and animals, and are essential to the normal functioning of the body. However, the actual definition of the term “essential” is not applied to all vitamins. Vitamin imbalances can be divided into three categories:
- 1.
Hypovitaminosis – shortage of one or more vitamins.
- 2.
Avitaminosis – depletion of one or more vitamins.
- 3.
Hypervitaminosis – excess of selected vitamins by overdose, and hence intoxication.
Altered maternal metabolism, growth of the conceptus and additional storage of some vitamins in the yolk sac and placenta, in particular vitamins A, B 1 , B 2 , B 3 , B 6 , B 12 , C, folic acid and minerals (calcium and iron), increase vitamin and mineral requirements during pregnancy.
A varied and balanced composition of the daily diet is the preferred basis for supplying vitamins and minerals. Folic acid may be the only vitamin identified to date that must be supplemented before and during pregnancy to prevent birth defects. However, questions have arisen with regard to additional supplementation of Vitamins A and D where an absence in the diet or lack of exposure to sunshine before and during pregnancy may occur. Researchers have demonstrated in countries with low dietary intake of vitamin A that supplementation with retinyl esters is critical for continued pregnancy and normal development ( ). Alternate sources of vitamin A are being developed as food sources, e.g. “golden” rice ( www.goldenrice.org ; ). There is always a concern that hypervitaminosis may produce toxicity for the newborn based upon animal studies; however, the dosages for producing such birth defects are usually extraordinarily high compared with the RDA.
In many countries, multivitamins/mineral tablets are used prior to, and during pregnancy, in order to provide coverage for any deficiencies in diet. It is commonly recommended that a daily prenatal vitamin tablet be taken and is recommended by the health care provider (HCP); as mentioned earlier the need for the multivitamin is often related to the need for prenatal folic acid supplementation (see Section 2.18.7 ). These recommendations may be especially important for the vegan and vegetarian who may not receive sufficient vitamins in their diets as well as appropriate amounts of iron.
A special note is added concerning gastric bypass surgery and pregnancy. Little information is specifically available for pregnant women; however, reviewed the population and stated: “The most common clinically relevant micronutrient deficiencies after gastric bypass include thiamine, vitamin B 12 , vitamin D, iron, and copper. Reports of deficiencies of many other nutrients, some with severe clinical manifestations, are relatively sporadic. Diet and multivitamin use are unlikely to consistently prevent deficiency, thus supplementation with additional specific nutrients is often needed. Though optimal supplement regimens are not yet defined, most micronutrient deficiencies after gastric bypass currently can be prevented or treated by appropriate supplementation.” This chapter will not directly address pregnant women following gastric bypass surgery; however, the reader will hopefully incorporate the above advise in the care of these women who may be planning a pregnancy or already pregnant.
Also, the use of dietary supplements for preventing postnatal depression does not appear to be effective based upon a recent Cochrane Report assessment ( ). In contrast, in another National Birth Defects Prevention Study ( ), results implied an association of nutrient intake with preterm deliveries.
2.18.1
Vitamin A (retinol)
Pharmacology
Vitamin A is a fat-soluble vitamin that occurs in two forms in nature. It ( retinol / retinal ) is found in food derived from animals, such as fish oils and liver. The body readily converts these forms to retinoids. Vitamin A values are expressed in different ways.
The nutrient was originally measured in IU (international units). In 1974, the United States began using a measurement called Retinol Equivalents (REs), where 1 RE = 1 μg of retinol, or 6 μg of β-carotene, or 3.333 IU of vitamin A. The recommended daily allowance for pregnant women is 700 RE.
Vitamin A can also be found in vegetables in the form of β-carotene or provitamin A. This form is found in plants, and is the precursor of the actual vitamin (retinol/retinal). Vitamin A is the basic substance needed for rhodopsin (visual purple). In addition, epithelial cells need vitamin A for growth and functional maintenance. Vitamin A, like vitamin C, accumulates in the embryo. The endogenous concentration of vitamin A metabolites in the serum is reduced in pregnant women during the first trimester, and amounts to between 0.26 and 7.7 μg/L. Even after 3 weeks of supplementation with 30,000 IU vitamin A per day, the peak values of the metabolites – retinoic acids ( tretinoin and isotretinoin ) are, at most, slightly above the concentrations measured previously ( ), or no different than noted in pregnant women who were not taking supplements ( ). During the second half of pregnancy, the endogenous concentration increases to about 150% of the level in nonpregnant women ( ).
Toxicology
The teratogenic action on humans of vitamin A derivatives, such as the retinoids (isotretinoin and acitretin ), which are used as therapy for severe forms of acne and psoriasis, is discussed in Chapter 2.17 . Retinoids are absolutely contraindicated during pregnancy.
About three decades ago, the possibility was first discussed that vitamin A preparations in doses over 25,000 IU daily might have a teratogenic action on humans similar to that of retinoids, and could cause characteristic “retinoid effects” ( ). At the end of the 1980s, manufacturers of multivitamin preparations in many countries changed the composition of their products, following the opinions of the Teratology Society and at the insistence of regulatory authorities, so that a daily dose did not contain more than 6,000 IU ( ). The safety of such doses has been confirmed repeatedly in many studies, among them the study on pregnant women in Hungary. Amazingly, a later study from the European Network of Teratology Information Services (ENTIS) gave no indication of a teratogenic effect, even with higher vitamin A doses (10,000–300,000, mean 50,000 IU per day), taken in the first trimester. In particular, the observations in another study that doses over 15,000 IU daily cause neural crest anomalies ( ) has been discredited based upon subjects not having the neural crest anomalies ( ). The ENTIS study of 423 pregnant women is the largest vitamin A study to date ( ). There was no increase in the rate of birth defects either among the 311 live-born children, or within the high-dose group of 120 children whose mothers took 50,000 IU daily. Nevertheless, looking at these case numbers statistically, they only allow for a relative risk above 2.8 to be ruled out.
A retrospective study discussed a higher risk for transposition of the great vessels with maternal vitamin A intake >10,000 IU daily during the 12 months prior to conception ( ). However, the number of affected children was low, and these results were not confirmed by other studies. Another retrospective study found no association between oral clefts and the (normal) vitamin A levels of women taking supplementation or consuming liver ( ).
There is a general warning against eating liver because a meal portion (100 g) may contain up to 400,000 IU; however, there is no clear indication yet of teratogenic effects from liver consumption. According to a pharmacokinetic study by , the peak value of vitamin A or of the ultimate teratogen, all-trans-retinoic acid, in the serum after eating liver is only 1/20 of that measured after taking vitamin A tablets. However, the three- to five-fold observed increase in plasma concentrations and the dose-dependent increase in exposure to 13-cis and 13-cis-4-oxo retinoic acid support the current safety recommendation: that women should be cautious regarding their consumption of liver-containing meals during pregnancy ( ).
β-carotene, also called pro-vitamin A, is converted as needed by the organism to vitamin A (retinol). Even high doses of β-carotene do not increase the retinol concentration in the serum and do not pose any teratogenic risk ( , ).
It must be re-emphasized that vitamin A deficiency is a serious condition as mentioned in the introduction above. Besides regions of the world deficient in vitamin A, another condition pregnancy following bariatric surgery may lead to vitamin A deficiency and should be monitored ( ).
Recommendation
A pregnant woman is recommended not to take more than 6,000 IU of vitamin A as retinyl esters, retinal or retinol per day. Basically, there is no reason to consume a vitamin A supplement, particularly when nutrition is reasonably well-balanced. Exceptions are, of course, illnesses where there is a proven deficiency – for example, as a result of limited intestinal absorption or living in an environment where food stuffs do not have adequate Vitamin A. If, however, a dosage of more than 25,000 IU per day has been given by accident, interruption of the pregnancy is not indicated. An individual risk assessment should be made using detailed fetal ultrasound. Potentially pregnant women should not eat liver. However, single liver meals do not require any action. β-carotene is safe to ingest during pregnancy.
2.18.2
Vitamin B 1 (thiamine)
Pharmacology and toxicology
Thiamine is important as a co-enzyme in carbohydrate metabolism. The need for vitamin B 1 (1–1.2 mg daily) does increase slightly during pregnancy, and there is a higher concentration in the fetal blood than in that of the mother. Even though thiamine supplementation is not usually discussed for hyperesis gravidarum treatment ( ), thiamine deficiency can induce clinical symptoms within 1 week. Severe polyneuropathy (Wernicke’s encephalopathy) can occur with chronic hyperemesis during pregnancy, and must be treated with thiamine supplementation ( , ) (see Chapter 2.4.6 ).
Recommendation
Supplementation with vitamin B 1 during pregnancy is, as a rule, unnecessary; however, for chronic hyperemesis gravidarum , thiamine supplementation should be instituted to prevent polyneuropathies. There are no clinical data suggesting teratogenicity with overdoses of thiamine.
2.18.3
Vitamin B 2 (riboflavin)
Pharmacology and toxicology
Riboflavin is an important co-enzyme in energy metabolism. No developmental disorders could be demonstrated in newborns whose mothers had clinical or laboratory signs of riboflavin deficiency ( ). In the same study, vitamin B 2 concentrations in the cord blood were four times higher than in the maternal blood. It would appear that there may be an active transplacental transport of vitamin B 2 , which prevents deficiency in the fetus. A suggestion has been made that riboflavin hypovitaminosis might be an additional risk factor for preeclampsia ( ).
Recommendation
Supplementation with vitamin B 2 during pregnancy is, as a rule, unnecessary when adequate dietary intake is available. Embryo- or fetotoxicity with an overdose of riboflavin has not been reported.
2.18.4
Vitamin B 3 (nicotinamide)
Pharmacology and toxicology
Nicotinamide is a constituent in many important enzymes. Deficiencies in pregnancy have not been reported.
Recommendation
Supplementation with vitamin B 3 during pregnancy is, as a rule, unnecessary. No adverse reactions are known.
2.18.5
Vitamin B 6 (pyridoxine)
Pharmacology and toxicology
Pyridoxine is the co-enzyme for some amino acid decarboxylases and transaminases. In North America, vitamin B 6 is used in combination with doxylamine as therapy for excessive vomiting in pregnancy (hyperemesis) (see Chapter 2.4 ). The vitamin B 6 concentration in the mother’s blood is reduced throughout the entire pregnancy. By contrast, the concentrations in the fetal blood are about three times higher ( ). There is no indication as yet for teratogenicity (see Chapter 2.4.5 ).
Recommendation
Supplementation with vitamin B 6 is only necessary in exceptional cases; for example, during tuberculostatic treatment with isoniazid (see Chapter 2.6 ). For treatment of nausea and vomiting in pregnancy, see Chapter 2.4 .
2.18.6
Vitamin B 12 (cyanocobalamin)
Pharmacology and toxicology
Vitamin B 12 ( cyanocobalamin ) is a factor in animal proteins necessary for the maturation of the erythroblasts. Its absence leads to megaloblastic (pernicious) anemia, with neurological consequences. Although the concentration of vitamin B 12 in the maternal serum drops slightly during the pregnancy, there is no reduction in the vitamin B 12 stored in the mother’s liver (about 3,000 μg). The newborn’s need for about 50 μg of stored vitamin B 12 is comparatively modest.
Diets in Western Europe commonly include 5–15 μg vitamin B 12 per day. The daily requirement for vitamin B 12 is 2 μg for nonpregnant women; during pregnancy this rises to 3 μg per day. Low vitamin B 12 levels have been discussed as a risk factor for early recurrent abortion ( ). Another genetic problem is transcobalamin II deficiency, which reduces the transfer of vitamin B 12 into the cell because of a lack of the carrier protein Transcobalamin II binding to Transcobalamin II receptors on cells especially the placenta. Interestingly, the placenta produces transcobalamin II and can provide sufficient transcobalamin II for the mother to overcome her transcobalamin II deficiency and thus low cellular levels of Vitamin B 12 . Low vitamin B 12 levels are measured directly in the blood; however, with vitamin B 12 deficiency in cells, one must monitor methylmalonic acid levels.
Recommendation
Because vitamin B 12 deficiency is not caused by pregnancy, supplementation with this vitamin is not routinely necessary. At most, it might be indicated with an unbalanced vegetarian or vegan diet. Anemia in the pregnancy caused by a vitamin B 12 deficiency should, of course, be treated.
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