Journal of the American College of Nutrition, Vol. 21, No. 1, 33-37 (2002)
Published by the American College of Nutrition
Vitamin Profile of 563 Gravidas during Trimesters of Pregnancy
Herman Baker, PhD, FACN,
Barbara DeAngelis, MPA,
Bart Holland, PhD,
Lisa Gittens-Williams, MD and
Theodore Barrett, Jr, MD
Department of Preventive Medicine and Community Health (H.B., B.D.A., B.H.), University of Medicine and Dentistry, New Jersey Medical School, Newark, New Jersey
Department of Obstetrics and Gynecology (T.B., L.G.-W.), University of Medicine and Dentistry, New Jersey Medical School, Newark, New Jersey
Address reprint requests to: Herman Baker, PhD, New Jersey Medical School, 65 Bergen St., GB159-SSB, Newark, NJ 07107
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ABSTRACT
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Objective: Gestation imposes metabolic stress on the mother which heightens as pregnancy progresses. The need for quantifying circulating vitamins is important for identifying pitfalls in metabolic imbalance and nutritional status. For this reason we wanted to analyze blood vitamin concentrations of B12, thiamin, biotin, pantothenate, B6, niacin, riboflavin, folate, vitamins A, C, E and total carotenes to determine if imbalances occur during the trimesters of pregnancy.
Methods: We randomly selected 563 gravidas who volunteered for this study from the obstetrical clinic of New Jersey Medical School; 132 were in 1st trimester, 198 were in 2nd trimester, and 233 were in 3rd trimester. All were healthy, taking a good diet and supplemented with vitamins. Blood, from an antecubital vein, was analyzed for thiamin, biotin, B12, B6, pantothenate, riboflavin, nicotinate, folates, vitamins A, E, C and total carotenes. Gravidas were classified as being normovitaminemic, hypervitaminemic or hypovitaminemic compared with blood vitamins seen in healthy non-pregnant, non-vitamin supplemented women.
Result: Hypervitaminemic levels of folate, biotin, pantothenate and riboflavin were found during any trimester of pregnancy due to vitamin supplementation. Despite the vitamin supplementation, a high percent of vitamin A, B6, niacin, thiamin and B12 hypovitaminemia was noted during pregnancy trimesters. An especially high percentage of niacin deficiency was seen during the 1st trimester; it worsened in later trimesters; B12 deficits increased during the late trimesters. Combination deficits of niacin, thiamin, vitamins A, B6, B12 were noted in each of the trimesters.
Conclusions: Despite vitamin supplementation, a vitamin profile of pregnancy indicates that vitamin deficits exist during the trimesters. Also, combination hypovitaminemias of deficient vitamins were noted; this indicates that a vitamin deficit during pregnancy does not occur in isolation.
Key words: pregnancy, vitamins, blood vitamin concentrations
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INTRODUCTION
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Gestation is more than the imposition of fetal growth upon the mother. Stress is exacerbated because maternal nutritional and physiologic demands heighten as pregnancy progresses. Growth and development of the fetus depend on the maternal supply of essential nutrients, e.g. vitamins [1–6]. An average 20% to 30% of pregnant women suffer from a vitamin deficiency; without prophylaxis, about 75% would show a deficit of at least one vitamin. Sequelae of some vitamin deficits during pregnancy, e.g. megaloblastosis, neural tube defects, placental and fetal defects, low birth weight and premature delivery, are still being studied [2]. In this report we analyze the blood of 563 gravidas grouped by trimester of pregnancy for 11 vitamins and total carotenes using proven sensitive and specific vitamin methodology [1,7,8]. This would provide an accounting of blood vitamin concentration of gravidas during the trimesters to use as a guide for identifying vitamin defects seen during pregnancy that might signal metabolic stress. A cross sectional study was chosen to allow us to profile, for the first time, the vitamin picture one might expect to see in a large group of gravidas in each trimester.
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MATERIALS AND METHODS
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For one year we randomly selected a total of 563 healthy gravidas who volunteered for this study. They represented 39% of the patients receiving care at our obstetrical clinic at the University Hospital of the New Jersey Medical School; 132 were in the 1st trimester, 198 were in the 2nd trimester and 233 were in the 3rd trimester of pregnancy. Each patient was given a general medical examination. Despite their low socio-economic status, all gravidas in the study were healthy with no overt nutritional stigmata. Gravidas having renal, metabolic, intestinal or liver disease, infections or taking medicines except vitamins were excluded. Patients received dietary needs and supplementation established by the Women, Infant, and Children (WIC) Program at our hospital center. Dietary intake of calories, protein, fat and carbohydrates from patients’ average 24-hour recall was calculated by the registered dietitians; based on this information, the dietitians concluded that the patients’ diets were not deficient. During each trimester routine blood chemistries revealed no gross aberrations. Daily ingestion of one supplemental vitamin-mineral pill (Materna®—Lederle Laboratories), as prescribed, was admitted. The vitamin-mineral supplementation used contained (as per label): 5000 IU vitamin A (50% as beta carotene), 400 IU vitamin D, 30 IU vitamin E, 120 mg vitamin C, 1.0 mg folic acid, 3.0 mg thiamin, 3.4 mg riboflavin, 10 mg vitamin B6, 12 µg vitamin B12, 20 mg nicotinamide, 30 µg biotin, 10 mg calcium pantothenate, 150 µg potassium iodide, 200 mg calcium carbonate, 27 mg ferrous fumarate, 25 mg magnesium oxide, 2.0 mg cupric oxide, 25 mg zinc oxide, 25 µg chromium chloride, 25 µg sodium molybdate, 5.0 mg manganese sulfate and 20 µg sodium selenite. A pill count, upon renewal, indicated full compliance by the gravidas. The age of the gravidas ranged from 20 to 39 years. After informed consent, maternal blood was drawn from an antecubital vein into Vacutainers (Becton Dickenson, Sunnyvale, CA) containing EDTA as anticoagulant. Blood was analyzed for thiamin, biotin, B12, B6, pantothenate, riboflavin and nicotinate concentration by vitamin sensitive and specific protozoologic methods [1,7,8]; folate was determined with Lactobacillus casei (ATCC #7469); vitamins A, E, C and total carotenes were analyzed by spectrophotometric methods. The sensitivity and specificity of these techniques used here for detecting vitamin deficits in biologic fluids and tissues have been validated [1,7,8]. On a micro-scale, protozoa respond to a great variety of vitamins in most of their molecular forms with a comprehensiveness matching chick, rat and HPLC chemical assays. Blood vitamin status of 83 non-vitamin supplemented, healthy, well-nourished, non-pregnant females, ages 24 to 36, was carried out. These current student volunteers provided a baseline reference range for comparing how pregnancy with vitamin supplementation influences blood vitamin concentrations. We classified gravidas in this study as being normovitaminemic (within the reference range), hypovitaminemic (below the reference range) or hypervitaminemic (above the reference range). Vitamin values for gravidas were listed in ascending and descending order and frequency of occurrence in the population in each trimester plotted. The mean (± SD) and 95% confidence limit were determined for each vitamin. A logarithmic distribution held for water-soluble vitamins and vitamin E; vitamin A and carotenes held as Gaussian distribution. The percentage of a single vitamin deficit during each trimester was calculated. The percentage of a paired multivitamin deficiency was also calculated by plotting the frequency of its occurrence in each trimester. All data were entered in Claris® and transferred to a SAS® database for analysis.
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RESULTS
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The vitamin means and ranges of the 563 healthy gravidas seen in each trimester are shown in Table 1. The percent of single vitamin deficits is shown in the 1st vitamin column of Table 2. In Table 2, the {+} indicates the specific vitamin deficit that was paired with the single deficit shown in the 1st vitamin column of the table. When the single vitamin deficit was paired with another vitamin deficit, e.g. niacin + B6, thiamin + B6 or vitamin A + thiamin, we could calculate the percent of specific multivitamin deficiencies (Table 2). Hypervitaminosis of folate, biotin, pantothenate and riboflavin is evident (Table 1). Despite vitamin supplementation a lower range & mean than the reference is noted for vitamins A, C, B6, B12, niacin and thiamin for each trimester hinting that a hypovitaminemia is hidden in these ranges (Table 1). Indeed, Table 2 indicates a high percent of single and multi-combination deficits of thiamin, niacin, vitamin A, B6, B12 during the trimesters of pregnancy. An especially high percent of single niacin deficit is seen during the 1st trimester; it becomes more severe as pregnancy progresses; it is the most prominent hypovitaminemia encountered during each trimester (Table 2). A vitamin B12 deficit is minimal during the 1st trimester but becomes more severe as pregnancy progresses (Tables 1 and 2). During the 1st trimester, gravidas have a 37% single niacin deficit, but it was not combined with a B12 deficiency; this contrasts with the increase of a niacin + B12 combination deficit seen during the 2nd and 3rd trimesters (Table 2). Niacin deficit is the most common part of the multivitamin deficit combinations seen in this study (Table 2). Single vitamin E, C and total carotene deficits are minimal during the trimesters (Table 2).
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DISCUSSION
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To our knowledge, this is the first study to record blood vitamin profile of gravidas grouped by trimester of pregnancy. Despite vitamin supplementation, deficiency of vitamin A, B6, niacin and thiamin is evident during all trimesters. B12 deficits increase during the 2nd and 3rd trimesters (Table 2) indicating that as pregnancy progresses the B12 demand by the fetus may be heightened. Vitamin deficiencies (Tables 1 and 2) suggest that as pregnancy proceeds it induces a maternal depletion of blood vitamins. A vitamin-depleted mother may give birth to a vitamin-depleted neonate. Such depletion may harbor metabolic consequences for the neonate [9]. The maternal vitamin depletion is not due to hemodilution common in pregnancy; vitamin concentrations are not greatly altered by such hemodilution [1,6]. One must note that despite hemodilution, total serum proteins did not change markedly from normal in these gravidas, e.g. 6–8 g/dL. Since circulating vitamins are bound to serum proteins [10] any deviation in vitamin concentration would result from vitamin availability per se, rather than from hemodilution. Others have observed this for trace metals, vitamins A and C and total carotenes during pregnancy [6,11].
Folic acid levels are above the upper-limits in each of the trimesters (Table 1). This stems from the high folate intake (1 mg) supplied by the vitamin supplement. High folate supplementation saturates blood folates for a prolonged interval; biotin, riboflavin and pantothenate show the same pattern (Table 1). These high blood levels indicate that vitamin malabsorption is probably not a factor for promoting vitamin deficits during pregnancy. Multivitamin deficit combinations of niacin, vitamins A, B12, B6 and thiamin are seen in each trimester of pregnancy (Table 2). This emphasizes that vitamin depletion during pregnancy does not occur in isolation. Increased placental vitamin transfer to the fetus may be responsible for depleting some vitamins in the mother; water-soluble vitamins do pass the placenta into the fetus from the maternal circulation with ease [9,12,13]. As mentioned for B12, perhaps the fetus requires more of specific vitamins, e.g. vitamin A, niacin, thiamin and B6, for metabolism and development during various trimesters of gestation (Table 2). It thus depletes these vitamins from the maternal circulation without producing overt clinical effects in the mother during the short time period required for pregnancy. Perhaps maternal tissue vitamins, e.g. those in the liver, are not yet depleted enough to produce overt clinical signs [7]. The high percent of subclinical niacin depletion seen in this study is puzzling; it has been reported earlier [3]. Niacin is essential for synthesizing NAD precursors. In pregnant rats, NAD precursors, e.g. niacinamide, are essential for maintaining fetal viability [2]. In contrast to studies on rats, we recorded no fetal or neonatal deaths during our study.
Given the striking prevalence of hypovitaminemias (Table 2), we noted no evidence of eclampsia, fetal stress, neonatal mortality or morbidity, or abnormal Apgar scores, agreeing with other workers [2,14]. Fifty-three neonates were of low birth weight (<1500 grams). We attempted to correlate low birth weights as well as parity, gestational age with changes in the key deficient nutrients, e.g. niacin, thiamin, vitamin A, B12 and B6; we found no statistical correlations using the Wilcoxon’s rank sum test. Such a conclusion might seem at odds with clinical wisdom; however, others have found positive [2,9,15,16] as well as negative vitamin correlations with birth weight [2,14]. Animal studies have shown this correlation, but results in humans still remain inconclusive [2]; it is always tempting to extrapolate experimental data from animals to humans. Unless the human mother is grossly undernourished, one could not anticipate an easily detectable influence of prenatal micronutrient aberration on fetal weight and gestation. Short of famine, or underreporting of energy intake, sub-clinical micronutrient depletions may not be prominent signals influencing birth weight [2,14,17–20]. Perhaps clearer correlations with factors involving pregnancy outcomes with hypovitaminemias might have emerged if we omitted vitamin supplementation during pregnancy. Obviously it would have been unethical to do so in order to sort out whether correlations could possibly imply causation.
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ACKNOWLEDGMENTS
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We thank The Healthcare Foundation of New Jersey for partial support of this study.
Received April 3, 2001.
Accepted October 25, 2001.
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TOP
ABSTRACT
INTRODUCTION
