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The Journal of Nutrition Vol. 127 No. 10 October 1997, pp. 1966-1972
Copyright ©1997 by the American Society for Nutritional Sciences

Vitamin B-12 Deficiency Is Very Prevalent in Lactating Guatemalan Women and Their Infants at Three Months Postpartum1,2,3

Jennifer E. Casterline, Lindsay H. Allen4, and Marie T. Ruel5

Department of Nutrition, Program in International Nutrition, University of California, Davis, CA 95616-8669 and * Instituto de Nutricion de Centro America y Panama, Guatemala City, Guatemala

ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGMENTS
FOOTNOTES
LITERATURE CITED

ABSTRACT

Vitamin B-12 status was evaluated in 113 Guatemalan women and their infants at 3 mo of lactation. Plasma vitamin B-12 was deficient or low in 46.7% of the mothers, and holotranscobalamin II (holo TC II) concentrations were low in 32.3%, which may indicate vitamin B-12 malabsorption. Only 9% had deficient or low plasma folate. Breast milk vitamin B-12 was low in 31%, and negatively correlated with infant urinary methylmalonic acid (UMMA, r = -0.22, P < 0.05, n = 88); UMMA was elevated in 12.2% of the infants, indicating vitamin B-12 deficiency. Mothers of the infants with elevated UMMA had significantly lower concentrations of vitamin B-12 in their breast milk compared with mothers of infants with normal UMMA concentrations (410.7 ± 247.7 vs. 705.3 ± 487.5 pmol/L, P = 0.05, n = 87). Mean maternal dietary intake of vitamin B-12 was significantly correlated with plasma vitamin B-12 (r = 0.20, P = 0.05, n = 94) and was the main determinant of plasma vitamin B-12 in a linear regression model. Determinants of maternal holo TC II concentrations included dietary intake of vitamin B-12 and Giardia lamblia infection. There were no statistically significant determinants of infant UMMA concentrations. We conclude that vitamin B-12 deficiency is highly prevalent in these lactating women and is associated with depletion of the vitamin in their infants. The cause of the maternal deficiency is unknown, but malabsorption exacerbated by low dietary intake of the vitamin is a possibility.

KEY WORDS: vitamin B-12 · folate · breast milk · infants · methylmalonic acid

INTRODUCTION

In two previous studies conducted in rural Mexico, we reported a high prevalence of vitamin B-12 deficiency (Allen et al. 1995, Black et al. 1994). In the first study, the Mexico Nutrition Collaborative Research Support Program (CRSP),6 vitamin B-12 deficiency was found in preschoolers, school-aged children, adults and pregnant and lactating women, with the prevalence ranging from 19 to 41% among these groups. In the second study, children received supplemental zinc and/or iron for a year, starting at 18-36 mo of age (Rosado et al. 1997). Vitamin B-12 deficiency was found in about 8% of the children, and low plasma vitamin B-12 in an additional 33%, at three different time points over the year. Plasma holotranscobalamin II (holo TC II) concentrations were low in 18-40% of the children. Holotranscobalamin II is thought to be an indicator of negative balance of vitamin B-12, which is usually caused by malabsorption (Herbert et al. 1990).

The purposes of the present study were 1) to investigate whether vitamin B-12 and folate deficiency and malabsorption are also common in a poor urban community in Guatemala, and 2) to investigate possible determinants of vitamin B-12 status of the mothers and infants, including anthropometry, biochemical indicators of nutritional status, maternal dietary intake and parasitic infections. Lactating women were chosen as subjects because this group had the highest prevalence of vitamin B-12 deficiency in the Mexico CRSP, and because it was also considered important to measure the association between maternal vitamin B-12 deficiency and vitamin B-12 status of breast-fed infants. Plasma folate concentrations were measured simultaneously in the assay for vitamin B-12 and malabsorption and deficiency of both vitamins have been reported in several studies. For example, in 29 Swedish children age 0.7-13.5 y (mean 3.3 y) with chronic giardiasis, subnormal fractional absorptions of folate and vitamin B-12 were present in one sixth and one third of the children, respectively (Hjelt et al. 1992). In Peruvian adults with megaloblastic anemia associated with chronic diarrhea and small bowel bacterial overgrowth, 64% had both low serum vitamin B-12 and folate, 20% had low serum vitamin B-12, and 16% had low serum folate alone (Frisancho et al. 1994).

There are few studies of vitamin B-12 status in infants, and most of these were conducted in infants born to strictly vegetarian mothers. Infants born to mothers whose vitamin B-12 status is inadequate are at high risk of developing a deficiency of the vitamin, because their stores are probably lower at birth and maternal breast milk concentrations are low (Allen 1994). Specker et al. (1988 and 1990a) showed that in vegan and omnivorous groups, the vitamin B-12 status of infants, assessed from their urinary methylmalonic acid (UMMA) concentrations, was associated with their mothers' serum vitamin B-12 concentration between 2 and 14 mo of lactation. Serum methylmalonic acid concentrations are thought to be a more sensitive indicator of vitamin B-12 status because they often become elevated before a fall in serum vitamin B-12 concentrations (Herbert et al. 1990), and evidence from a study of an elderly population suggests that the same is true for UMMA concentrations (Norman and Morrison 1993). Assessing infants' vitamin B-12 status with UMMA provides the advantage that blood samples are not required.

It is important to diagnose vitamin B-12 deficiency in infants because it can result in neurobehavioral disorders. Children born with low vitamin B-12 stores show developmental problems within the first 4-8 mo of life (Allen 1994). Symptoms include decreased ability to concentrate, depression, problems with abstract thought, and memory impairment and confusion (Lindenbaum et al. 1988). These sequelae could be particularly damaging to rapidly developing infants. Severe vitamin B-12 deficiency could also result in anemia.

MATERIALS AND METHODS

Subjects and location. Participants were residents of Santa Elena, a poor, peri-urban community on the outskirts of Guatemala City. The community health clinic served as the research headquarters. This cross-sectional study was added to a randomized double-blind trial designed for other purposes, in which mothers (n = 130) were given either a daily zinc supplement (15 mg/d) or a placebo, between 30 and 60 d postpartum. All of the mothers in this study were also in the zinc supplementation trial. Mothers were recruited when they came to the clinic to register their child, an event which is compulsory by 15 d after birth. All women in this community register their children because they believe strongly that this offers some protection against child robbery. Premature and/or low-birth-weight infants were not included in the study. After the zinc study ended at 2 mo of lactation, 113 lactating women and their infants entered into the present study at 3.0 ± 0.5 mo of lactation. The protocol was approved by the Human Subjects Review Committee at the University of California, Davis, and at the Instituto de Nutricion de Centro America y Panama (INCAP), Guatemala City, Guatemala.

Anthropometry, socioeconomic status and parity. Anthropometric data were collected by two anthropometrists who were trained (Lohman et al. 1988) and standardized (Habicht 1974) using standard techniques, and included height and weight of the mothers, and recumbent length and weight of the infants, measured to the nearest gram and millimeter, respectively. Z-scores for weight-for-age, length-for-age, and weight-for-height were calculated by comparing individual values to the WHO/Centers for Disease Control reference data (WHO 1979). Socioeconomic status was measured using a short questionnaire, and from this a variable was generated based on whether the women had the following items in or at their household: a car, bicycle, motorcycle, sewing machine, radio, television, stereo, refrigerator or a lamp. Data on the number of pregnancies and on living and deceased children were collected from the mothers.

Dietary information. To obtain information on maternal dietary energy, protein, vitamin B-12 and folate intake, dietary data were collected as a 24-h recall from the women on two separate occasions at 1 and 2 mo postpartum. The weight of food consumed was derived from a combination of weighing the foods at the household when available, asking the mothers about portions consumed, and obtaining an average weight of produce at local markets. The nutrient composition of these foods was then estimated using the WorldFood Dietary Assessment program (WFDAP, Murphy et al. 1994). All of the foods were included in the analysis, and 204 out of the 220 foods consumed were identical to those in the WFDAP. The nutrient composition of the remaining 16 foods came from the following sources: Survey 7 (n = 5 foods, USDA 1991), Handbook 8 (n = 6, USDA 1976), and the INCAP food composition database (n = 5 fruits and vegetables, Flores et al. 1971). The INCAP food composition database does not have information on the vitamin B-12 or folate content of foods.

Inadequate intakes of vitamin B-12 and folate were calculated using two methods. The first is called the probability of deficiency, which was estimated by the WFDAP. The calculation follows the probability approach recommended by the National Research Council (1986) and requires in the calculation estimates of the mean and SD of the nutrient requirements. The approach is discussed in more detail by Calloway et al. (1993) and Murphy et al. (1995) and is based on the WHO requirements (FAO/WHO 1988) for vitamin B-12 (1.3 µg/d) and folate (270 µg/d) in lactation. The second method compares the average dietary intakes to 2/3 of the U.S. RDA for vitamin B-12 (2.6 µg/d) and folate (280 µg/d, Food and Nutrition Board 1989).

All infants were completely breast-fed when this study was conducted, so that breast milk was their only source of vitamin B-12. Mothers did not take vitamin B-12 supplements during pregnancy or lactation.

Collection of blood, breast milk, urine and feces. All samples were taken between 0800 and 1000 h. A blood sample (10 mL) was drawn from the women when not fasting, with EDTA as an anti-coagulant. A milk sample was collected by complete expression of one breast, using an electric breast pump (Egnell Inc., Cary, IL), while the child was nursing from the opposite breast to stimulate a let-down reflex. Based on results from a validation study conducted in this population (Ruel et al. 1997), samples were collected from the opposite breast from the one used for the last feed, and at least 1.5 h after the last feed. Each sample was covered in aluminum foil and kept on ice prior to freezing within 4 h. Women were asked to bring a stool sample, which was screened for ova and parasites using microscopy at INCAP.

A urine sample was collected from each infant. The urine was collected into plastic bags attached to the male infants, and in plastic containers placed under the female infants. Samples were stored at -20°C until they were hand-carried frozen to the University of California, Davis, and stored at -20°C until analyzed.

Biochemical analyses. Hemoglobin and hematocrit concentrations were measured in whole blood using a HemoCue (HemoCue Inc., Mission Viejo, CA) and a microcentrifuge, respectively. The cut-off values used to define anemia were hemoglobin <= 122 g/L and hematocrit <= 0.365, which included an adjustment for the altitude of 1500 m (WHO 1972). Plasma vitamin B-12, holo TC II and folate and breast milk vitamin B-12 were measured by the MAGIC Vitamin B-12/Folate radioassay (Ciba-Corning Diagnostics, Medfield, MA). The reported intraindividual and interindividual CV were <5% based on five individuals and <6% based on 12 samples, respectively. Holotranscobalamin II has been proposed as a sensitive measure of negative vitamin B-12 balance because vitamin B-12 is most rapidly depleted from holo TC II when its absorption is low (Herbert et al. 1990). Holotranscobalamin II was measured after mixing 1 mL of plasma with microfine glass, which binds apo- and holo TC II, leaving TCI and III. Vitamin B-12 bound to TCI and III was analyzed and holo TC II calculated by difference from total plasma vitamin B-12 (Vu et al. 1993).

Cut-off values for plasma vitamin B-12 are defined as deficient (<= 147.7 pmol/L) and low (147.7-221.3 pmol/L; WHO Scientific Group 1968). A plasma concentration of holo TC II >= 45.0 pmol/L is necessary to sustain erythrocyte concentrations of vitamin B-12 in the normal range (Tisman et al. 1993), and this concentration was the cut-off used for this study. There are no generally accepted cut-offs for deficient or low breast milk vitamin B-12 concentrations. However, infant UMMA excretion increased when breast milk concentrations were <362 pmol/L in a group of vegan and omnivorous women (Specker et al. 1990a). The normal range for UMMA in infants is 0.4-23 µmol/mmol creatinine (Specker et al. 1990b), so 23 µmol/mmol creatinine was used as the cut-off for this ratio. Plasma folate concentrations are defined by the manufacturers of the radioassay to be deficient at <= 6.1 nmol/L and low at 6.1-8.4 nmol/L.

Table 1. Descriptive statistics on Guatemalan lactating women and their infants at 3 mo postpartum

[View Table]

Table 2. Mean and prevalence of deficient and low biochemical and hematological values in Guatemalan lactating women and their infants at 3 mo postpartum

[View Table]

Methylmalonic acid in the infant urine samples was extracted with ethyl acetate and then dried and derivatized with monodansylcadaverine and dicyclohexylcarbodiimide (Babidge and Babidge 1994). Methylmalonic acid was measured by HPLC with a fluorescence detector and expressed as a ratio of µmol/L methylmalonic acid to mmol/L creatinine (Sigma Diagnostics, St. Louis, MO).

Statistical analyses. Statistical analyses were performed using SAS (version 6.04, SAS Institute, Cary, NC). When the distributions were skewed, variables were transformed using either a log or square root transformation. Spearman correlation analyses tested associations between maternal biochemical, hematological and breast milk measures, socioeconomic status, parity, dietary intake of vitamin B-12 and folate, and infant UMMA. Student's t test was used to determine differences in any of the variables due to the previous zinc supplementation, plasma holo TC II concentrations between those with low or deficient compared with normal plasma vitamin B-12 concentrations, and plasma vitamin B-12 and infant UMMA concentrations of mothers with low holo TC II concentrations based on whether or not the mothers had low or adequate dietary intakes of vitamin B-12. Student's t test was also used to test the statistical significance of differences in maternal and infant biochemical variables due to parasites in general or to specific parasites including Giardia lamblia, Ascaris lumbricoides and Endolimax nana. These were tested individually because they were the most prevalent parasitic infections. Stepwise linear and logistic regression models (Neter et al. 1985) were used to determine the main determinants of maternal plasma vitamin B-12, holo TC II and folate, breast milk vitamin B-12 and infant UMMA concentrations. Maternal hemoglobin and hematocrit concentrations were controlled for in the multiple regression models.

RESULTS

Characteristics of the mothers and infants at 3 mo are described in Table 1. There was no significant difference in plasma vitamin B-12 or folate concentrations due to the zinc supplements. However, both hemoglobin (12.76 ± 1.38 vs. 13.69 ± 1.45 g/L, P < 0.003) and hematocrit (0.39 ± 0.02 vs. 0.40 ± 0.02, P < 0.02) were significantly lower in those women who received zinc supplements between 30 and 60 d postpartum compared with the placebo group.

Mean concentrations of plasma vitamin B-12 and folate and hematological measures are presented in Table 2, with prevalences of deficient and low concentrations. About one third of the mothers had low plasma vitamin B-12, and an additional 13% had concentrations in the deficient range. Approximately one third of the mothers had a low breast milk vitamin B-12 concentration (Fig. 1). Anemia, found in 24.7% of the women, was less prevalent than low plasma vitamin B-12 concentrations.

Fig. 1. Cumulative frequency of vitamin B-12 concentrations in breast milk samples from Guatemalan lactating women (n = 92). A suggested adequate concentration is >= 362.0 pmol/L (Specker et al. 1990a).
[View Larger Version of this Image (14K GIF file)]

Holotranscobalamin II concentrations were low in a third of the mothers and were significantly lower in women with low vs. normal plasma vitamin B-12 compared with normal concentrations (40.3 ± 22.5 vs. 86.8 ± 48.5 pmol/L, P < 0.0002) and in those with deficient vs. normal vitamin B-12 concentrations (29.9 ± 18.5 vs. 71.6 ± 44.3 pmol/L, P < 0.0002). The correlation between plasma vitamin B-12 and holo TC II was r = 0.72 (P < 0.0001, n = 97, Table 3). Women with low plasma folate had lower plasma vitamin B-12 (r = 0.45, P < 0.0001, n = 95, Table 3) and holo TC II (r = 0.31, P < 0.003, n = 97, Table 3) concentrations, although only 9% of the women had low plasma folate. Those with a low hematocrit had low plasma vitamin B-12 (r = 0.30, P < 0.003, n = 96), holo TC II (r = 0.26, P < 0.02, n = 99) and folate (r = 0.24, P < 0.04, n = 96) and a low hemoglobin concentration (r = 0.75, P < 0.0001, n = 81, Table 3).

Table 3. Correlation matrix of biochemical, hematological, dietary, parity and anthropometric variables from Guatemalan lactating women and their infants

[View Table]

Surprisingly, breast milk vitamin B-12 concentrations were not significantly correlated with maternal plasma vitamin B-12 or holo TC II concentrations. As expected, maternal breast milk vitamin B-12 was negatively correlated with infant UMMA:creatinine concentrations (r = -0.22, P < 0.05, n = 88, Table 3). In addition, mothers of the 12.2% of infants with elevated UMMA had significantly lower concentrations of vitamin B-12 in their breast milk than mothers of infants with normal UMMA concentrations (410.7 ± 247.7 vs. 705.3 ± 487.5 pmol/L, P = 0.05, n = 87, Fig. 2).

Fig. 2. Urinary methylmalonic acid (UMMA) concentrations in infants fed by mothers with low or normal breast milk vitamin B-12 concentrations (410.7 ± 247.7 vs. 705.3 ± 487.5 pmol/L, P = 0.05, n = 87).
[View Larger Version of this Image (13K GIF file)]

Maternal nutrient intake data are presented in Table 1. Maternal dietary vitamin B-12 intake averaged 3.90 ± 12.00 µg/d with a median of 1.47 µg/d, and was significantly correlated with plasma vitamin B-12 (r = 0.20, P = 0.05, n = 94) concentrations. The five highest contributors to vitamin B-12 intake were beef liver, beef kidney, goose liver, dried fish and sardines in tomato sauce. Four women consumed on average more than 47 µg/d, because of their high intakes of beef liver, beef kidney, dried fish or pork sausage on the days when dietary data were collected. The mean intakes of vitamin B-12 and energy were significantly correlated (r = 0.30, P < 0.003, n = 96), as were intakes of vitamin B-12 and protein (r = 0.35, P < 0.0005, n = 96). Folate consumption averaged 241.9 ± 111.1 µg/d, and was significantly correlated with plasma folate concentration (r = 0.37, P < 0.0003, n = 96, Table 3). Three women were high consumers of folate, but they were not the same women with high vitamin B-12 consumption. Folate intake was not related to consumption of any particular foods. Plasma folate was weakly associated with mean energy (r = 0.19, P < 0.07, n = 96) and protein (r = 0.20, P < 0.06, n = 96) intake. The inadequate dietary intakes based on calculated probabilities of deficiency and 2/3 of the U.S. RDA for vitamin B-12 and folate were 38.6 ± 37.6 and 47.1 ± 36.3% and 60.5 ± 49.1 and 32.6 ± 47.0%, respectively.

Women with low holo TC II concentrations and vitamin B-12 intakes less than 1.3 µg/d had significantly lower plasma vitamin B-12 concentrations (147.6 ± 0.97 vs. 192.7 ± 1.0 pmol/L, P < 0.02) compared with women with adequate vitamin B-12 intakes.

There were no significant correlations between socioeconomic status and any of the maternal or infant biochemical indices or with mean dietary vitamin B-12 or folate. Parity was negatively correlated with maternal dietary intake of vitamin B-12 (r = -0.23, P < 0.01, n = 126), and weakly with maternal hematocrit (r = -0.19, P < 0.06, n = 100) and with infant UMMA (r = -0.24, P < 0.02, n = 98), weight-for-age (r = -0.22, P < 0.03, n = 101) and length-for-age (r = -0.23, P < 0.03, n = 101, Table 3).

The frequency of women infected with parasites was as follows: Giardia lamblia (9.6%), Ascaris lumbricoides (14.9%), Trichuris trichura (3.2%), Iodameba buetschlii (5.3%), Endolimax nana (13.8%), Entamoeba histolytica (2.1%), and Blastocystis hominis (4.3%); 43% of women were infected with at least one parasite. Women infected with Giardia lamblia (n = 9) had holo TC II concentrations that were approximately 50% of those of uninfected women (31.9 ± 12.6 vs. 67.6 ± 10.5 pmol/L, P < 0.06, n = 94), but this difference was not significant. The presence of parasites showed no significant association with any other maternal biochemical variable.

The stepwise linear regression models revealed that dietary vitamin B-12 intake was the main predictor (P < 0.05) in a model to determine plasma vitamin B-12 concentrations, using dietary vitamin B-12 intake, zinc supplementation status, parity, socioeconomic status, age of the mother, maternal weight and height, and parasites as possible determinants. Although an indicator of malabsorption would be ideal in this model, holo TC II was not included because of its high correlation with plasma vitamin B-12; holo TC II constitutes 20% of total plasma vitamin B-12. In a similar model for holo TC II concentrations, dietary intake of vitamin B-12 and Giardia lamblia infection were the significant determinants (P < 0.05). Breast milk vitamin B-12 concentrations had no significant determinants. There were no significant determinants of infant UMMA concentrations. The only significant predictor for maternal plasma folate concentration was dietary folate intake (P < 0.003). The logistic regression model did not converge for any of the biochemical variables.

DISCUSSION

There is a high prevalence of vitamin B-12 deficiency in this group of Guatemalan lactating women and an association between maternal breast milk vitamin B-12 concentrations and depletion in infants. The lack of association between maternal plasma and breast milk vitamin B-12 concentrations is somewhat puzzling, because a significant correlation has been reported in other studies. However, in the Mexico Nutrition CRSP, there was a marginally significant relation (r = 0.48, P = 0.06, n = 50) between the two variables at 204 ± 30 d of lactation, in milk samples consisting of 5 mL of foremilk plus 5 mL of hindmilk and in serum collected from fasting mothers. One possible explanation is that the relationship is stronger in women with poorer vitamin B-12 status than found in this study; Specker et al. (1990a) found a strong association between maternal plasma and breast milk vitamin B-12 in 19 strict vegetarians, many of whom had a much lower plasma vitamin B-12 concentration than these Guatemalan women.

The significant inverse correlation between breast milk vitamin B-12 concentration and infant UMMA excretion is consistent with studies conducted by Specker et al. (1988 and 1990a) and suggests that low maternal vitamin B-12 status and intake during pregnancy and lactation is associated with vitamin B-12 depletion in the infants. Specker et al. (1990a) found that maternal breast milk vitamin B-12 concentrations were more strongly correlated with infant UMMA when the concentration in breast milk was <= 362 pmol/L. This pattern did not occur in the present study, even though 29 women had concentrations below this cut-off and the variance in their breast milk vitamin B-12 concentration was smaller.

There is no generally accepted value for adequate breast milk vitamin B-12 concentrations, due to differences in the assays used among investigators and the small number of studies. In one study, concentrations of vitamin B-12 in breast milk in women in the United States ranged from 221 to 738 pmol/L (n = 21, 2-30 mo postpartum, Sandberg et al. 1981). Concentrations at 3 mo of lactation in the current study ranged from 177 to 2466 pmol/L, (mean = 690 ± 491 pmol/L) and were higher than those found in the Mexico CRSP at 204 ± 30 d postpartum (mean = 390 ± 236 pmol/L). Trugo and Sardinha (1994) showed in the only longitudinal study of breast milk vitamin B-12 that concentrations decrease during the first 3 mo of lactation. No longer-term longitudinal data are available. However, other investigators have reported that there is no further decrease during lactation in cross-sectional studies up to 30 mo postpartum (Donangelo et al. 1989, Trugo et al. 1988, Sandberg et al. 1981). In a group of well-nourished Brazilian women, there was no difference in vitamin B-12 concentration between morning, afternoon and evening collections, or between right or left breasts, or between foremilk and hindmilk samples. Intraindividual coefficients of variation within a day ranged from 0 to 83%, but there was no trend throughout the day (Trugo and Sardinha 1994). This suggests that it does not matter the time of day that breast milk samples are taken, but variability will be high, making it difficult to find significant associations with breast milk vitamin B-12 concentrations.

Infants born to well-nourished mothers have about 25 µg of vitamin B-12 stores at birth, which should be adequate to maintain infant vitamin B-12 status until the end of the first year of life even if breast milk concentrations are low (Allen 1994). However, an infant born to a vitamin B-12-deficient mother will accumulate less stores in utero and may require more breast milk vitamin B-12 to prevent deficiency. Even the mother with the lowest concentration of breast milk vitamin B-12 in our study (177 pmol/L) should have provided her infant with 0.19 µg vitamin B-12/d, assuming a breast milk intake of approximately 800 mL/d by infants 3-5 mo of age in developing countries (Brown et al. 1997). On the basis of the breast milk vitamin B-12 concentrations of the women in this study, 16.3% of the infants would have had intakes below the RDA of 0.3 µg/d. All would have had an intake higher than the WHO recommendation of 0.1 µg/d (FAO/WHO 1988), a value selected because it reverses clinical symptoms in infants with vitamin B-12 deficiency.

The causes of the vitamin B-12 deficiency in this study are unknown. Several lines of evidence suggest that low maternal dietary intake of the vitamin B-12 was a risk factor: 1 ) dietary vitamin B-12 intake was predicted to be inadequate in 39 and 60% of the women, based on the probability of deficiency and 2/3 of the U.S. RDA, respectively, and was the only significant predictor of plasma vitamin B-12 concentrations and 2 ) within the group of women with possible vitamin B-12 malabsorption (i.e., low holo TC II concentrations), those with a low intake of the vitamin had significantly lower plasma vitamin B-12 concentrations. However, malabsorption of vitamin B-12 is also implicated by the lower holo TC II concentrations observed in women infected with Giardia lamblia, the fact that Giardia lamblia was a predictor of holo TC II concentrations in the linear regression model, and the high prevalence (33%) of low plasma holo TC II. Our data support the hypothesis that a combination of low dietary vitamin B-12 intake and malabsorption are risk factors for the vitamin deficiency. Whether any malabsorption is solely attributable to Giardia lamblia is uncertain, because only nine of the women were infected with this parasite. Bacterial overgrowth (Saltzman and Russell 1994) and Helicobacter pylori (Carmel et al. 1994) have also been associated with vitamin B-12 malabsorption, but these were not investigated in this study.

Vitamin B-12 and folate have been shown to be malabsorbed simultaneously during Giardia lamblia infection (Hjelt et al. 1992), and this could explain the correlation between plasma vitamin B-12 and folate concentrations. However, the correlation could also be explained by similar consumption patterns of the two vitamins; 47.1 ± 36.3% of women were predicted to have inadequate intakes of folate and 38.6 ± 37.6% consumed inadequate amounts of vitamin B-12, although low plasma folate was much less prevalent than low plasma vitamin B-12. In addition, dietary intake of folate was the main predictor of plasma folate concentrations, and intakes of vitamin B-12 and folate were significantly correlated. Therefore, it cannot be determined from the results of this study whether the association between low plasma vitamin B-12 and folate was due to simultaneous malabsorption or low dietary intakes.

There is a need to investigate the global prevalence of vitamin B-12 deficiency, to determine its causes and to evaluate the effect of vitamin B-12 supplementation in developing countries. Because of the potential serious consequences of vitamin B-12 deficiency for infants, studies should be conducted in other developing countries to evaluate vitamin B-12 status during the perinatal period and its relation to cognitive or neuromotor performance of neonates.

ACKNOWLEDGMENTS

We wish to thank Diana Marroquin and Milagro de Castillo at INCAP, Guatemala City, Guatemala, for organizing and conducting the field work, Flori Cano at INCAP for the parasite analyses, Janet Peerson in the Program of International Nutrition at the University of California, Davis, for her statistical assistance, Stephen Dueker at UC Davis for his technical assistance with the MMA analyses and Natalie Studer for analyzing the infant urinary creatinine concentrations. In addition, we also wish to thank the mothers and their infants for their participation.

FOOTNOTES

1   Presented in part at the International Conference of the Society for Research in Human Milk and Lactation, July 1995, Tlaxcala, Mexico and at Experimental Biology 96, April 1996, Washington, DC [Casterline, J. E., Ruel, M., Marroquin, D. & Allen, L. H. (1996) Vitamin B-12 deficiency in Guatemalan lactating women and their infants. FASEB J. 10: 1673 (abs.)].
2   Supported by USAID grant no. DAN-5063-A-00-1115196.
3   The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.
4   To whom correspondence and reprint requests should be addressed.
5   Current address: IFPRI, 1200 Seventeenth St. NW, Washington, DC., 20036-3006.
6   Abbreviations used: CRSP, Collaborative Research Support Program; UMMA, urinary methylmalonic acid; INCAP, Instituto de Nutricion de Centro America y Panama; WFDAP, WorldFood Dietary Assessment program; TC, transcobalamin.

Manuscript received 24 March 1997. Initial reviews completed 16 May 1997. Revision accepted 23 June 1997.

LITERATURE CITED

0022-3166/97 $3.00 ©1997 American Society for Nutritional Sciences



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[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
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 J. Nutr.Home page
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[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
K. M. Jones, M. Ramirez-Zea, C. Zuleta, and L. H. Allen
Prevalent Vitamin B-12 Deficiency in Twelve-Month-Old Guatemalan Infants Is Predicted by Maternal B-12 Deficiency and Infant Diet
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[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
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Multiple micronutrients in pregnancy and lactation: an overview
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Home page
 J. Nutr.Home page
K. G. Dewey, R. J. Cohen, and K. H. Brown
Exclusive Breast-Feeding for 6 Months, with Iron Supplementation, Maintains Adequate Micronutrient Status among Term, Low-Birthweight, Breast-Fed Infants in Honduras
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[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
A.-L. B. Monsen, H. Refsum, T. Markestad, and P. M. Ueland
Cobalamin Status and Its Biochemical Markers Methylmalonic Acid and Homocysteine in Different Age Groups from 4 Days to 19 Years
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[Abstract] [Full Text] [PDF]

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 J. Nutr.Home page
S. P. Murphy and L. H. Allen
Nutritional Importance of Animal Source Foods
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[Abstract] [Full Text] [PDF]

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 Am. J. Clin. Nutr.Home page
S. Villalpando, M. E Latulippe, G. Rosas, M. J. Irurita, M. F. Picciano, and D. L O'Connor
Milk folate but not milk iron concentrations may be inadequate for some infants in a rural farming community in San Mateo, Capulhuac, Mexico
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[Abstract] [Full Text] [PDF]

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 J. Nutr.Home page
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B Vitamins: Proposed Fortification Levels for Complementary Foods for Young Children
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[Abstract] [Full Text] [PDF]

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 Am. J. Clin. Nutr.Home page
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Vegetarianism and vitamin B-12 (cobalamin) deficiency
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Homocysteine and methylmalonic acid in diagnosis and risk assessment from infancy to adolescence
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[Abstract] [Full Text] [PDF]

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 Am. J. Clin. Nutr.Home page
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High prevalence of cobalamin deficiency in Guatemalan schoolchildren: associations with low plasma holotranscobalamin II and elevated serum methylmalonic acid and plasma homocysteine concentrations
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[Abstract] [Full Text] [PDF]

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 Am. J. Clin. Nutr.Home page
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Lack of hemoglobin response to iron supplementation in anemic Mexican preschoolers with multiple micronutrient deficiencies
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