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OCR for page 336
17
Vitamins A, E, and K
In this chapter, the subcommittee reviews data relating to supplemen-
tation of the fat-soluble vitamins A, E, and K during pregnancy. Vitamin
D, another fat-soluble vitamin, is reviewed in conjunction with calcium in
Chapter 16, because calcium metabolism is dependent on that vitamin. The
fat-soluble vitamins are often considered together since their absorption,
transport, and excretion are influenced by their very limited solubility in
water.
VITAMIN A
The term vitamin A includes a number of closely related compounds
with similar biologic activities. This group of compounds is important
throughout life because of their participation in a variety of biologic func-
tions, including vision, reproduction, immune function, and cellular growth
and differentiation. Two groups of compounds are related to vitamin A: the
rei'noids (called preformed vitamin A if they possess vitamin A activity) and
the carotenoids (called precursors of vitamin A or provitamin A if they can
be metabolized to an active form of the vitamin). The naturally occurring
forms of retinoids include retinal, retinaldehyde, and retinoic acid. The
primary form of preformed vitamin A is retinyl ester, which is found in
foods of animal origin such as liver, fish liver oils, milk, eggs, and butter.
Provitamin A carotenoids are mainly of vegetable origin; carrots and dark-
green leafy vegetables are especially rich sources. Nutritional needs for
vitamin A can be met by ingesting either preformed retinoids with vitamin
336
OCR for page 337
VITAMIN A, E' ID K
337
A activity or certain carotenoids, such as carotene, that can be metabolized
to vitamin ~
After ingestion, between 70 and 90% of preformed vitamin A is ab-
sorbed, whereas the absorption of carotenoids is less efficient and more
variable, ranging from 20 to 50%. Retinyl esters are hydrolyzed, reester-
ified, and transported in chylomicrons to the liver. Carotenoids can be
converted to retinal and retinyl esters in the intestinal mucosa, and both
carotenoids and the retinyl esters derived from them are transported via
the chylomicrons to the liver. The major storage site is the liver, which
normally contains more than 90% of the total body stores of vitamin A in
well-nourished people. Adipose tissue and the kidney are minor storage
sites.
The liver releases a complex of retinal and retinol-binding protein
(RBP). This complex combines with transthyretin in the blood, is circulated,
and may be either extracted by tissues or remetabolized by the liver and
excreted in bile.
Importance
From a public health standpoint, vitamin A is of greatest importance
in maintaining visual function. Worldwide, vitamin A deficiency results
in approximately 250,000 to 500,000 cases of visual impairment per year,
primarily in children in developing countries (FAO, 1988; Sommer, 1982~.
Thus, vitamin A deficiency appears to be a major public health problem in
many parts of the world (Araujo et al., 1986, 1987; Sklan, 1987; Stanton et
al., 1986; Villard and Bates, 1987) but is not common in the United States.
The most widely recognized effect of vitamin A is in the retina, where
it is involved in photochemical reactions with rhodopsin (Wald, 1968~. It
also functions throughout the body in aiding glycoprotein synthesis and
promoting cellular growth and differentiation.
Vitamin A During Pregnancy
There is only limited information regarding the effect of pregnancy
on the metabolism and physiology of vitamin A. Some evidence suggests
that the retinol-RBP complex may be different In pregnant women than in
nonpregnant controls (Sklan et al., 1985~. Data from studies of pregnant
sheep support the possibility that binding proteins in the fetus may be
different from those in the adult (Donoghue et al., 1982~.
Quantitation of the rates at which vitamin A is transferred from mother
to fetus is difficult and has largely been limited to animals. The rate at
which retinoic acid is transferred to the fetal rat may be lower than that of
retinyl ester (Shukla et al., 1986~. Studies in vitamin A-sufficient pregnant
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338
DIETARY INTAKE AND NUTRIENT SUPPLEMENTS
sheep suggest that transport of vitamin A to the fetus increases but that
efficiency of transfer decreases when high levels of vitamin A are provided
to the ewe (Donoghue et al., 1985), suggesting that there may be some
placental regulation of transport.
Several mechanisms proposed for the transfer of retinol to the fetus are
based primarily on animal data. One possibility is the direct transfer of the
retinol-RBP complex. Alternatively, placental uptake of retinol, transient
esterification in the placental tissues, and release of retinol into the fetal
circulation may be involved; this was observed in sheep by Donoghue et al.
(1982) and in rats by Torma and Vahlquist (1986~. Data on both sheep and
rats suggest that a dynamic equilibrium exists between mother and fetus
and that there is substantial transfer in both directions (Donoghue et al.,
1982, 1985; Ismadi and Olson, 1982~.
Once transferred into the fetus, some retinol is stored in the fetal
liver. Wallingford and Underwood (1986) reported that maternal vitamin
A supplementation did not increase fetal hepatic retinol levels in rats. In
human fetuses, such hepatic concentrations are consistently much lower
than those in adults (Montreewasuwat and Olson, 1979; Shah et al., 1987;
Wallingford and Underwood, 1986) and correlate with maternal serum
retinol levels (Shah et al., 1987~. An intercountry comparison of fetal liver
tissue showed a significant increase in hepatic vitamin A levels in Swedish
but not Ethiopian fetuses during the second and third trimesters compared
with first-trimester levels (Gebre-Medhin and Vahlquist, 1984~.
Units of Measurement
Chemical and pharmacologic diversity among the compounds with
vitamin A activity has led to the use of different units to express vitamin
A activity international units (IUs) and retinol equivalents (REs). An IU
is defined in terms of the growth-promoting activity of 0.30 ,ug of all-`rans
retinol or 0.60 ,ug of all-trans p-carotene. The RE was adopted to account
for the difference in the intestinal absorption of retinol and carotene. One
RE is equal to 1 fig of all-trans retinol, and biologically, 1 RE is assumed
to be equivalent to 6 fig of all-1rans ,~?-carotene (NRC, 1989~. At present,
the RE is preferred, although IUs have been widely used in the past and
are still reported. Because of ambiguities in converting from one system to
another, the use of IUs is retained in this chapter if that was the unit of
measurement used in the report that is referenced.
Criteria for Deficiency
Assessment of vitamin A status is complicated by the chemical and
pharmacologic diversity among the compounds with vitamin A activity.
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VITAMIN A, E, AND K
339
Methods to assess deficiency include biologic measurements such as bio-
chemical measurements of plasma retinal level or liver concentrations of
vitamin A and functional tests such as correction of impaired dark adapta-
tion.
Plasma retinal concentrations can be widely used as a basis for clinical
determination of vitamin A status. In normal nonpregnant adults, impaired
dark adaptation may result at retinal concentrations below 15 ~g/dl (Hume
and Krebs, 1949), and abnormal electroretinograms may be found at levels
below 4 to 11 ~g/dl (Sauberlich et al., 1974~. Levels below 30 ,ug/dl have
been associated with vitamin A-responsive anemia, and levels of 7 to 37
,ug/dl, with follicular keratosis (Sauberlich et al., 1974~. In Recommended
Dietary Allowances (RDAs) it is recommended that nonpregnant adults
maintain plasma retinal concentrations higher than 30 ~g/dl in order to
maintain body stores; levels less than 20 ~g/dl are associated with increased
risk for development of clinical signs and symptoms of vitamin A deficiency
(NRC, 1989~.
Pregnancy complicates the interpretation of these values, in part be-
cause blood levels of REP change with pregnancy (NRC, 1978~. In re-
search settings, liver stores of vitamin A have been used to assess vitamin
A status-100 ,ug/g is typical of well-nourished, nonpregnant adults.
Measurement of dark adaptation has also been used for screening
vitamin A deficiency (Hume and Krebs, 1949~. A more recent method of
measuring dark adaptation has been reported as a practical and reliable
method requiring only limited technology (Villard and Bates, 1986~. From
a public health standpoint, this type of assessment may be of considerable
value.
Vitamin A appears to be important for fetal growth. In a study
of mother-infant pairs in an undernourished population, poor maternal
vitamin A status was associated with preterm birth, intrauterine growth
retardation, and decreased birth weight (Shah and Rajalakshmi, 1984~. In
a human autopsy series, maternal serum retinal correlated positively with
fetal weight (Shah and Rajalakshmi, 1984; Shah et al., 1987~. Chytil (1985)
provided evidence that vitamin A may be important for lung growth in
human fetuses. Similarly, studies in several animal species, including rats
and domestic farm animals, suggest positive correlations of vitamin A with
fetal growth. In rats, maternal vitamin A deficiency was correlated with
decreased fetal body and organ size (Khanna and Reddy, 1983; Reddy and
Khanna, 1983; Sharma and Misra, 1986; ~kahashi et al., 1975~.
Recommended Intakes
Estimates of vitamin A intakes required to maintain desirable retinal
levels have been somewhat variable, ranging from 500 to 1,200 RE/day
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340
DIETARY INTAKE AND NUTRIENT SUPPLEMENTS
(FAO 1988; NRC, 1989; Sauberlich et al., 1974). The RDA for vitamin
A is 800 RE for nonpregnant women in the childbearing years and is not
increased during pregnancy (NRC, 1989).
Vitamin A deficiency is rare in the United States, and evidence suggests
that U.S. women have adequate liver stores of the vitamin. Fetal vitamin A
requirements are very low until the third trimester, and even then they are
estimated to increase maternal vitamin A requirements by only 9% (NRC,
1989). There is no persuasive evidence that the dietary requirement for
vitamin A is increased during pregnancy.
Teratogenicity and Toxicity
It is apparent that vitamin A deficiency affects the human fetus; how-
ever, an excess of retinoids has also been of considerable concern, partic-
ularly regarding the possibility of teratogenicity (see review by Teratology
Society, 1987~. Isotretinoin, a synthetic relative of vitamin A (Accutane(~,
13~s-retinoic acid), has been reported to be teratogenic in animals and
humans in the first trimester (Teratology Society, 1987~. The typical pheno-
type includes such central nervous system abnormalities as hydrocephalus
or microcephaly, cardiovascular abnormalities, facial anomalies (e.g., of
the ear and palate), and altered growth. A high incidence of spontaneous
abortion has also been reported.
Large doses of retinal or retinyl esters may result in a similar syndrome
(Rosa et al., 1986; Stange et al., 1978; Teratology Society, 1987; Woollam,
1985~. Retinoic acid also appears to be teratogenic (Lammer et al., 1985~.
The minimum teratogenic dose is not known. A wide range of maternal
vitamin A intakes has been reported in these studies. Of particular concern
is the association of a first-trimester 2,000-IU vitamin A supplement with
phenotypic isotretinoin syndrome (Lungarotti et al., 1987~. However, most
other observers suggest that an intake of at least 20,000 to 50,000 IU is
required for teratogenicity. Whether or not lower doses produce a less
evident clinical syndrome is not known.
Ingestion of excessive amounts of preformed vitamin A produces a
well-defined syndrome, including headache, vomiting, diplopia, alopecia,
liver damage, and skin abnormalities (Bauernfeind, 1980~. These toxic
reactions appear to require a sustained total dietary intake of preformed
vitamin A in excess of 15,000 RE in adults. It is not known whether
pregnancy alters the maternal clinical syndrome of vitamin A toxicity.
In contrast, limited data on humans suggest that high intakes of
carotenoids are not teratogenic or toxic to either mother or fetus. In
nonpregnant adults, very large intakes of carotenoids do not appear to
be harmful, primarily because large doses are inefficiently absorbed and
converted to vitamin A.
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VITAMIN A, E, AND K
341
Usual Intake
Usual intakes of vitamin A by pregnant women are discussed in Chap-
ter 13. As mentioned above, the average vitamin A intake in the United
States appears to exceed the RDA for both pregnant and nonpregnant
women.
Rush et al. (1988) showed that the average vitamin A intake of low-
income women in the United States exceeds the RDA' even before the
women enter the Supplemental Food Program for Women, Infants, and
Children. Finley et al. (1985) reported that the average dietary intake of
vitamin A by complete vegetarians appears to be somewhat higher than
that of the average U.S. population. However, since there is also a wide
range of individual intakes, it may be important to assess vitamin A intakes,
particularly in women with unusual diets or who habitually avoid dietary
sources of vitamin ~
Recommendations for Supplementation
Since estimated dietary intake in the United States appears to be suf-
ficient to meet the needs of most pregnant women throughout gestation,
routine supplementation during pregnancy is not recommended. Carefully
supervised supplementation may be desirable for some groups of pregnant
women in the United States, for example, for recent emigrants from coun-
tries in which vitamin A deficiency is endemic. Information and opinion on
the teratogenic risk of various forms of vitamin A are rapidly evolving, and
supplementation of vitamin A should be approached with caution until the
risk is clarified.
VITAMIN E
Vitamin E is required by most animal species, although the recognition
of its importance in humans is relatively recent. This vitamin is biologically
important as an antioxidant; i.e., it traps free radicals and prevents oxi-
dation of unsaturated fatty acids. Manifestations of its deficiency include
anemia, neuromuscular abnormalities, and reproductive failure. In humans,
vitamin E deficiency has been demonstrated in premature infants, mani-
fested primarily by anemia (Oski and Barness, 1967), and in patients with
prolonged, marked fat malabsorption, usually accompanied by necrologic
abnormalities (Kelleher et al., 1987; Muller, 1986; Sokol et al., 1985~. Many
other functions have been attributed to vitamin E, both in the medical and
lay literature, but these effects remain unproven and controversial.
I\vo classes of compounds, tocopherols and tocotrienols, include bio-
logically active forms of vitamin E. Both classes are characterized chemically
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342
DIETARY INTAKE AND NUTRIENT SUPPLEMENTS
by a similar ring system, but they differ in the saturation of the side chain.
The tocopherols act-, ,0-, by-, and b-), which have a saturated side chain, are
widely found in nature. c~-ldcopherol is both the most active and the most
prevalent biologic form.
Normal bile secretion and pancreatic function are required for intesti-
nal absorption of vitamin E. After absorption, vitamin E is carried in the
blood in the lipoproteins, primarily in high-density lipoproteins in women
but in low-density lipoproteins in men (Behrens et al., 1982~. As a fat-
soluble compound, tocopherol is widely distributed in the fatty component
of tissues. Its concentration is similar in most tissues if expressed relative
to their fat content.
Vitamin E is widely distributed in the polyunsaturated fatty acids
(PUFAs) of cell membranes. Deficiency of vitamin E permits oxidation
of PUFAs, with consequent damage to membranes and cells. Although
vitamin E selves as the primary antioxidant system, ascorbic acid and
selenium also serve this purpose.
Importance
Blood tocopherol levels increase during pregnancy, paralleling a rise
in total lipid levels (Ho~witt et al., 1972; NRC, 1978~. Vitamin E deficiency
is not known to be of special concern for pregnant women or their fetuses.
Although vitamin E has not been a major issue in obstetrics and is not
believed to be related to the risk of preterm birth, it has attracted consider-
able interest in the care of newborns, particularly those born prematurely.
Premature infants occasionally develop a hemolytic anemia, which is gen-
erally believed to be due to vitamin E deficiency. Thus, the vitamin is given
to premature infants routinely to meet their special needs (AAP/ACOG,
1988~. The limited evidence that macrocytic anemia results from vitamin
E deficiency is based primarily on hemolysis after an in vitro peroxide
stress. This anemia seldom occurs in full-term neonates or infants (Cruz
et al., 1983; Hassan et al., 1966; Linderkamp, 1987; Oski and Barness,
1967; Vanderpas and Vertongen, 1985~. However, although the clinical
syndrome of anemia is well known, more recent studies have questioned
whether this anemia results from vitamin E deficiency (Zipursky et al.,
19874. Linderkamp (1987) has pointed out, quite correctly, that many
features are unique to the red cells of newborn infants a factor that
complicates interpretation of study results.
Vitamin E may be involved in several other serious problems of prema-
ture infants, such as bronchopulmona~y dysplasia, a common form of lung
disease. Early enthusiasm for treating this disorder with therapeutic doses
of vitamin E has waned (Ehrenkranz et al., 1979, 1982; McCarthy et al.,
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VITAMIN A, E, AND K
343
1984; Wender et al., 1981; Zoberlein et al., 1982). Similarly, there is con-
siderable controversy regarding a role for therapeutic doses of vitamin E in
reducing retinopathy of prematurity (retrolental fibroplasia), an infrequent
but serious condition leading to substantial visual impairment (Bremer et
al., 1986; Hittner et al., 1984; Kretzer et al., 1985; Phelps et al., 1987;
Rosenbaum et al., 1985~. Evidence has also been presented that vitamin
E may be protective in reducing intraventricular hemorrhage in newborn
infants (Chiswick et al., 1983; Speer et al., 1984) and microcephaly in rats
(Tanaka et al., 1986~. Studies of the use of vitamin E in the treatment of
these clinical problems have produced inconsistent results, and vitamin E
supplementation of preterm infants remains highly controversial (see re-
views by Karp and Robertson, 1986; Pereira and Barbosa, 1986; and Phelps,
1987~. Attempts to treat diseases of preterm infants with intravenous vi-
tamin E have resulted in major morbidity and mortality (Martone et al.,
1986~. However, this is now attributed to a stabilizer in the preparation,
rather than to the vitamin itself (Alade et al., 19864.
There is no evidence that maternal vitamin E supplementation would
reduce the incidence of health problems in premature infants. However, if
the fetus acquires vitamin E while it is accumulating fat (during the last 8
to 10 weeks of gestation), the premature infant may be especially low in
vitamin E. The full-term infant may therefore have larger vitamin E stores
than preterm infants, but the stores are still low compared with those of
adults (Gross and Melhorn, 1972~. Vitamin E status is difficult to interpret
in human fetuses and newborns, in part because both serum lipids and
serum levels of vitamin E are low (All et al., 1986; Desai et al., 1984;
Huijbers et al., 1986; Ostrea et al., 1986; Schulz et al., 1986~.
Criteria for Deficiency
In clinical assessment, blood concentrations of tocopherol in normal
adults range from 0.5 to 1.2 mg/dl. The tocopherol concentration relates
directly to the concentration of total plasma lipids and should be expressed
in relation to total lipids.
Recommended and Usual Intakes
The RDA for vitamin E is based on estimates of customary intakes of
the vitamin from balanced diets in the United States (NRC, 1989~. Actual
requirements have not been estimated because of methodologic di~culties.
There is significant variation in the tocopherol content of foods. Vegetable
oils are the richest source of vitamin E in the U.S. diet. Margarine,
shortening, wheat germ, whole grains, and nuts contain large amounts
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344
DIETARY INTAKE AND NUTRIENT SUPPLEMENTS
of vitamin E. Substantial loss of tocopherol may occur with processing,
storage, and food preparation.
Vitamin E appears to be safe over a wide range of intakes, and
no chemical or clinical evidence of toxicity has been observed with oral
vitamin E in dosages to 800 mg/day in nonpregnant adults (Farrell and
Bieri, 1975~. Intake varies widely within and among diets, but appears to
average 5 to 11 mg/day for adults eating a typical mixed diet. As noted
in Chapter 13, the dietary intake of vitamin E may be difficult to assess
because of methodologic and reporting problems. The estimated mean
intake by pregnant women in the United States ranges from 3 to 9 mg/day,
which is below the pregnancy RDA of 10 ma. The vitamin E intake of well-
nourished pregnant and lactating women in England has also been reported
to be below the RDA, but without evident clinical signs or symptoms (Black
et al., 1986~.
Recommendations for Supplementation
In pregnant women, there have been no definable deficiency syndromes
for vitamin E, and intakes below the RDA have not been accompanied by
an obvious clinical morbidity. Thus, supplementation of healthy pregnant
women appears to be unnecessary.
Special Considerations
Given the low vitamin E levels and the clinical syndrome of anemia
believed to result from vitamin E deficiency, it is routine to give premature
infants supplements of vitamin E.
VITAMIN K
Vitamin K is a fat-soluble vitamin that is required for the synthesis
of prothrombin and clotting factors VII, IX, and X. Additional vitamin K-
dependent proteins are found in bone, kidney, and other tissues. Natural
forms include phylloquinone of plant origin and a group of menaquinones
of bacterial origin. Menadione is a fat-soluble synthetic compound with
vitamin K activity; several water-soluble derivatives of menadione are also
available.
Vitamin K can be absorbed from the small intestine. Efficient absorp-
tion occurs in the presence of normal biliary and pancreatic function. The
vitamin is widely distributed among tissues; the highest concentration is
found in the liver. The body pool of vitamin K is small, and its turnover is
rapid (Bjornsson et al., 1980~.
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~IIAMIN A, E, AND K
345
Vitamin K is contained in a variety of foods, especially leafy vegetables,
dairy products, meat, and eggs. Bacterial flora of the small intestine are
another source of vitamin K activity. Analyses of liver compounds with
vitamin K activity indicate that food and bacteria provide the normal adult
with roughly equal amounts of vitamin K (Rietz et al., 1970~.
Importance
The specific importance of vitamin K during pregnancy is largely
undetermined. It is known that vitamin K levels and the levels of vitamin
K-dependent clotting factors are low in the human fetus (Pietersma-de
Bruyn and van Haard, 1985~. Transport of vitamin K from mother to fetus
has received little attention, but it appears to be limited (Hamulyak et al.,
1987, Hiraike et al., 1988~. The process of fetal and neonatal clotting is
very complicated, and specific clinical problems with bleeding in the fetus
are rare. The existence of vitamin K deficiency in the fetus is uncertain
(Israels et al., 1987~.
By contrast, there is considerable evidence that the newborn infant is
functionally vitamin K-deficient, as judged both by vitamin K levels and by
abnormal clotting (Lane and Hathaway, 1985; Muntean, 1983; Pietersma-
de Bruyn and van Haard, 1985; Prentice, 1985~. Accordingly, pediatric
and obstetric professional groups recommend that all newborns receive
parenteral vitamin K immediately after birth (AAP/ACOG, 1988), whether
maternal dietary intake is high or low.
Criteria for Deficiency
Data on plasma vitamin K levels are not systematically available. Vita-
min K status is traditionally assessed by blood clotting time. Prolongation
of clotting resulting from deficiency of vitamin K-dependent factors is
considered to be presumptive evidence of vitamin K deficiency.
Recommended and Usual Intake
The requirement for vitamin K is difficult to estimate, partly because
of technical problems. Although a 65-,ug RDA for vitamin K has been
established for adults, a different recommendation has not been made for
vitamin K intake during pregnancy (NRC, 1989~.
Normal newborns are routinely given 0.5 to 1.0 mg of vitamin K as phy-
tonadione in a single dose immediately following birth. Hemolytic anemia,
hyperbilirubinemia, and kernicterus have been reported in newborns who
were given menadione (Owen, 1971~. These complications are uncommon
today, however, since other forms of vitamin K are in current use.
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346
DIETARY INTAKE AND NUTRIENT SUPPLEMENTS
Vitamin K intake has not been investigated in nationwide studies of
nutrient intake. Estimates for usual intake from a mixed diet in the United
States range from 300 to 500 Friday (Olson, 1987~.
Recommendations for Supplementation
No vitamin K supplement is indicated in the routine care of pregnant
women. No general public health problems have been associated with
vitamin K deficiency, which is limited to individuals with disorders that
cause substantial degrees of malabsorption or alterations of gut flora. There
does not appear to be a need to supplement normal pregnant women with
vitamin K, but treatment with vitamin K may be advisable as a part of the
medical therapy for pregnant women with malabsorption or those who are
undergoing treatment with antibiotics. Vitamin K status should be carefully
assessed in patients taking prothrombin~epressing anticoagulants, such as
coumarin. Vitamin K may also be of special importance in newborns born
to women taking anticonvulsant drugs (Yerby, 1987~.
CLINICAL IMPLICATIONS
· Routine supplementation with vitamin A, either as retinal (pre-
formed vitamin A) or carotene (its precursor), appears to be unnecessary
in the United States, because the usual dietary intake is adequate to meet
the needs of most pregnant women.
· Because of uncertainties about the teratogenicity of preformed
vitamin A, use of supplemental retool is discouraged during the first
trimester of pregnancy unless there Is evidence of deficiency.
.
Although it is routine to supplement premature infants with vitamin
E, evidence does not support routine supplementation of pregnant women
with this vitamin.
· Although it Is advisable that all newborns receive vitamin K at
birth, evidence does not indicate that pregnant women should be provided
with supplemental vitamin K.
REFERENCES
AAP/ACOG (American Academy of Pediatrics/American College of Obstetricians and
Gynecologists). 1988. Guidelines for Perinatal Care, 2nd ed. American Academy of
Pediatrics, Elk Grove, Ill. 356 pp.
Alade, S.L., R.E. Brown, and A. Paquet, Jr. 1986. Polysorbate 80 and E-Ferol toxicity.
Pediatrics 77:593-597.
All, J., H.A. Kader, K Hassan, and H. Arshat. 1986. Changes in human milk vitamin E
and total lipids during the fimt twelve days of lactation. Am. J. Clin. Nutr. 43:925-930.
Araujo, R.L., M.B.D.G. Araujo, R.O. Sieior, R.D.P. Machado, and B.V Leite. 1986.
Diagnostico da situac~ao da hipovitaminose a e da anemia nutricional na populaces
do vale do Jequitinhonha, Minas Gerais, Brasil. Arch. Latinoam. Nutr. 36:642-653.
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VITAMIN A, E, AND K
347
Araujo, R.L., M.B.D.G. Araujo, R.D.P. Machado, A.N Braga, B.V. Leite, and J.R. Oliveira.
1987. Evaluation of a program to overcome vitamin A and iron deficiencies in areas
of poverty in Minas Gerais, Brazil. Arch. Latinoam. Nutr. 37:9-22.
Bauernfeind, J.C. 1980. The Safe Use of Vitamin A. A Report of the International Vitamin
A Consultative Group (IVACG). We Nutrition Foundation, Washington, D.C. 44 pp.
Behrens, WA., J.N. Thompson, and R. Madere. 1982. Distribution of ct-tocopherol in
human plasma lipoproteins. Am. J. Clin. Nutr. 35:691-696.
Bjornsson, T.D., P.J. Meffin, S.E. Swezey, and T.F. Blaschke. 1980. Disposition and turnover
of vitamin K1 in man. Pp. 328-332 in J.W. Suttie, ed. Vitamin K Metabolism and
Vitamin K-Dependent Proteins. University Park Press, Baltimore.
Black, A.E., S.J. Wiles, and A.A. Paul. 1986. The nutrient intakes of pregnant and lactating
mothers of good soc~o-economic status in Cambridge, UK: some implications for
recommended daily allowances of minor nutrients. Br. J. Nutr. 56:59-72.
Bremer, D.L~, G.L~ Rogers, H. Bell, and R. Lytle. 1986. The efficacy of vitamin E in
retinopathy of prematurity. J. Pediatr. Ophthalmol. Strab. 23:132-136.
Chiswick, M.L^, M. Johnson, C. Woodhall, M. Gowland, J. Davies, N. Toner, and D. Sims.
1983. Protective effect of vitamin E on intraventricular haemorrhage in the newborn.
Ciba Found. Symp. 101:186-200.
Chytil, F. 1985. Vitamin A and lung development. Pediatr. Pulmonol. l:S115-S117.
Cruz, C.S.D., P.D. W~mberley, K Johansen, and B. Friis-Hansen. 1983. The effect of
vitamin E on erythrocyte hemolysis and lipid peroxidation in newborn premature
infants. Acta Paediatr. Scand. 72:823-826.
Desai, I.D., F.E. Martinez, J.E. Dos Santos, and J.E. Dutra de Oliveria. 1984. Transient
lipoprotein deficiency at birth: a cause of low levels of vitamin E in the newborn.
Acta Vitaminol. Enzymol. 6:71-76.
Donoghue, S., D.W. Richardson, D. Sklan, and D.S. Kronfeld. 1982. Placental transport of
retinol in sheep. J. Nutr. 112:2197-2203.
Donoghue, S., D.W. Richardson, D. Sklan, and D.S. Kronfeld. 1985. Placental transport of
retinol in ewes fed high intakes of vitamin A. J. Nutr. 115:1562-1571.
Ehrenkranz, R.A., R. C. Ablow, and J.B. Warshaw. 1979. Prevention of bronchopulmonary
dysplasia with vitamin E administration during the acute stages of respiratory distress
syndrome. J. Pediatr. 95:873-878.
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Representative terms from entire chapter:
dietary intake
