Vitamin A is a fat-soluble vitamin that occurs in two forms in nature. It is found in food derived from animals, such as fish oils and liver. The body readily uses this form. Vitamin A values are expressed in different ways.
The nutrient was originally measured in IU (international units), but in 1974 the United States began using a measurement called Retinol Equivalents (REs), where 1 RE = 1 pg of retinol, or 6|ig of ,1-carotene, or 3.333 1U 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 |3-carotene or provitamin A. This form is found in plants, and is the precursor of the actual vitamin. 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 7.7pg/l. Even after 3 weeks of supplementation with 30000 IU vitamin A per day, the peak values of the metabolites retinoic acid and isotretinoin are, al most, slightly above the concentrations measured previously (Wicgand 1998). During the second half of pregnancy, the endogenous concentration increases to about 150% of the level in nonpregnant women (Malone 1975).
The teratogenic action on humans of vitamin A derivatives such as the retinoids isotretinoin and acitretin, which arc 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" (Rosa 1986). 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 6000 1U (Teratology Society 1987). The safety of such doses has been confirmed repeatedly in many studies, among them the Dudas (1992) 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 high doses (i.e. over 15 000 IU daily) cause neural crest anomalies (Rothman 1995) could not be confirmed (Miller 1998). The ENTIS study of 423 pregnant women is the largest vitamin A study to date (Mastroiacovo 1999). 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 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 (Botto 2003). However, the number of affected children was low, and these results are 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 (Mitchell 2003).
There is a general warning against eating liver, because a 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 Buss (1994), 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 (Hartniann 2005).
i-carotene, also called pro-vitamin A, is converted as needed by the organism to vitamin A (retinol). Even high doses of ;l-carotene do not increase the retinol concentration in the scrum and do not pose any teratogenic risk (Miller 1998: Poiifka 1996).
Recommendation. A pregnant woman should not take more than 6000 IU of vitamin A as retinyl esters, retinal or retinol per day. Basically, there is no reason to take 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, if, however, a dosage of more than 25 000 1U per day has been given by accident, interruption of the pregnancy is in no way 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. 3-carotene is safe during pregnancy.
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