Beruflich Dokumente
Kultur Dokumente
Anemia and Deficiencies of Folate and Vitamin B-6 Are Common and Vary
with Season in Chinese Women of Childbearing Age1
Alayne G. Ronnenberg,* Marlene B. Goldman, Iain W. Aitken* and Xiping Xu**2
*Department of Population and International Health, Department of Epidemiology and **Department of
Environmental Health and the Program for Population Genetics, Harvard School of Public Health, Boston,
MA 02115
KEY WORDS:
China
women
folic acid
vitamin B-12
vitamin B-6
iron
ABSTRACT Little is known about the micronutrient status of Chinese women of childbearing age. We assessed
nonfasting plasma concentrations of folic acid, vitamin B-12, vitamin B-6 (as pyridoxal-5-phosphate), hemoglobin
(Hb), ferritin and transferrin receptor (TfR) in 563 nonpregnant textile workers aged 2134 y from Anqing, China. All
women had obtained permission to become pregnant and were participating in a prospective study of pregnancy
outcomes. Mean (SD) plasma concentrations were 9.7 (4.1) nmol/L folic acid, 367 (128) pmol/L vitamin B-12, 40.2
(15.8) nmol/L vitamin B-6, 108 (12.9) g/L Hb, 42.6 (34.2) g/L ferritin and 5.2 (2.7) mg/L TfR. Twenty-three percent
of women had biochemical evidence of folic acid deficiency, 26% were deficient in vitamin B-6 and 10% had low
vitamin B-12. Overall, 44% of women were deficient in at least one B vitamin. Although anemia (Hb 120 g/L) was
detected in 80% of women, only 17% had depleted iron stores (ferritin 12 g/L); 11% had elevated TfR
concentrations. Distinct seasonal trends were observed in the prevalence of moderate anemia (Hb 100 g/L) and
deficiencies of folic acid and vitamin B-6, with significantly lower concentrations of folate and Hb occurring in
summer and lower concentrations of vitamin B-6 occurring in winter and spring than in other seasons. We conclude
that deficiencies of folic acid, vitamin B-6 and iron were relatively common in this sample of Chinese women of
childbearing age and were contributing to the high prevalence of anemia. Without appropriate supplementation,
these deficiencies could jeopardize the womens health and increase their risk of adverse pregnancy
outcomes. J. Nutr. 130: 27032710, 2000.
1
Supported in part by grant 1R01HD/OH32505 from the National Institute of
Child Health and Human Development.
2
To whom correspondence should be addressed.
3
Abbreviations used: BMI, body mass index; Hb, hemoglobin; LBW, low birth
weight; NTD, neural tube defects; TfR, transferrin receptor.
RONNENBERG ET AL.
2704
TABLE 1
Characteristics of Chinese women in the study
Characteristic
Age, y
Height, cm
Weight, kg
Body mass index, kg/m2
25.0 1.51
157.7 5.01
49.2 5.91
19.8 2.11
%
6
396
156
5
1.0
70.3
27.7
0.9
22
51
424
43
23
3.9
9.1
75.3
7.6
4.1
41
405
117
7.3
71.9
20.8
459
61
12
2
25
82.1
10.9
2.2
0.4
4.5
550
4
9
2
97.7
0.8
1.6
0.4
1 Means SD.
RESULTS
The demographic characteristics of the study population
are presented in Table 1. Most women (90%) were between
23 and 28 y old, and 95% had a BMI of 23 kg/m2. Because
eligible women were married, had obtained permission to
become pregnant and were planning to become pregnant in
the near future, only 18% reported the current use of any type
of contraceptive. Only 2% indicated they used nutrient supplements of any kind.
High prevalence of micronutrient deficiencies and anemia. Although mean folic acid and vitamin B-6 concentrations were within the normal range, deficiencies of these
vitamins were observed in 23 and 26% of women, respectively
(Table 2). Ten percent of women had combined deficiencies
of folic acid and vitamin B-6, and 39% were deficient in either
folate or vitamin B-6. Low plasma concentrations of vitamin
B-12 were observed in 10% of women. Overall, 44% of women
were deficient in at least one B vitamin, although 2% were
deficient in all three. The mean concentration of folic acid was
significantly lower in women in the lowest BMI quintile
(18.02 kg/m2) than in those in the upper four quintiles (8.7
3.4 versus 10.0 4.2 nmol/L, P 0.001). In addition, the
prevalence of folate deficiency decreased significantly across
BMI quintiles from 30% in the lowest quintile to 17% in the
highest quintile (P for trend 0.02). The prevalence of
vitamin B-12 deficiency, however, increased across BMI quintiles from 5% in the lowest quintile to 19% in the highest (P
for trend 0.0002). Vitamin status was unrelated to age,
education, menstrual characteristics or contraceptive use.
Among the 557 women for whom Hb concentration was
available, 80% were anemic, with Hb below the established
World Health Organization cutoff value of 120 g/L (Table 2).
As shown in the distribution of Hb concentration (Fig. 1),
nearly 60% of women had an Hb concentration of 100 119
g/L, and 20% had 100 g/L; only 5% had 90 g/L. Plasma
ferritin and TfR concentrations were determined in a subset of
499 women for whom adequate plasma samples were available.
Of these, 17% had a ferritin concentration of 12 g/L,
indicating iron depletion (Table 2), and an additional 19%
had a ferritin concentration of 1224 g/L, indicative of low
but not yet depleted stores; 11% of women had elevated TfR.
Overall, 22% of women had either low ferritin or elevated
TfR. Mean TfR concentration was significantly higher among
women with depleted iron stores than among women with
ferritin of 12 g/L (Table 3). Furthermore, 33% of women
with depleted iron stores, and 24% with ferritin of 20 g/L
had elevated TfR concentrations, indicating functional iron
deficiency. Among women with elevated TfR, 51% also had
depleted iron stores. No relation was observed between age,
BMI, education, contraceptive use, menstrual cycle length or
number of bleeding days per cycle and either mean concentrations of Hb, ferritin and TfR (ANOVA P 0.05) or the
Education completed
Elementary
Middle School
High School
College and above
Menstrual cycle length, d
2023
2426
2730
3135
36
Bleeding days per cycle,
23
46
7
Contraceptive use
None
Condom
Oral contraceptive pill
Intrauterine device
Other (unspecified)
Vitamin supplement use
None
Multivitamin and/or B vitamins
Vitamin C, E or A
Current use of alcohol
563
563
562
562
2705
TABLE 2
B Vitamin, hemoglobin, ferritin and transferrin receptor (TfR)
concentrations and percentage of Chinese women with
abnormal values
Variable
n1
Means
SD
Median
Abnormal2
%
563
563
563
557
499
499
9.7 4.1
367 128
40.2 15.8
108 12.9
42.6 34.2
5.2 2.7
9.1
350
38.4
105
36
4.6
23.1
9.8
25.6
80.1
16.8
10.6
RONNENBERG ET AL.
2706
depleted iron stores and 80% were anemic. Because our subjects had already obtained the government permission that is
required in China before having a child, most will attempt to
become pregnant during subsequent months. Unless periconceptional supplementation is initiated, many women will enter
pregnancy with severely compromised micronutrient status,
which will likely deteriorate further in response to the physiologic demands of gestation, thereby increasing their risk of
adverse pregnancy events.
We found strong evidence that the prevalence of moderate
anemia and deficiencies of both folate and vitamin B-6 varies
according to season. Zheng et al. (1989) also reported seasonal
variations in folate status among subjects in Linxian, China,
with lower red cell folate observed between April and August
compared with September through March, which is consistent
with our finding of lower plasma folate during summer. To our
knowledge, ours is the first report of seasonal variation in
vitamin B-6 status from China. Understanding seasonal variations in nutritional status is particularly important in women
of childbearing age because some evidence suggests that perinatal outcomes, including perinatal death, also vary by season
(Zhang et al. 1991).
The high prevalence of deficiencies of folic acid or vitamin
B-12 (30%) among women who may be attempting to become
pregnant poses particular reproductive risks given recent findings that relate poor periconceptional folate (Czeizel and Dudas 1992, Mills et al. 1995) and vitamin B-12 (Kirke et al.
1993, Steen et al. 1998) status to the occurrence of NTD and
other birth defects (Shaw et al. 1995). Reports indicate that
NTD occur more frequently in rural areas (Hu et al. 1996, Lian
et al. 1987, Wang et al. 1996) and Northern provinces (Berry
et al. 1999, Moore et al. 1997) of China than in Western
countries, and there is evidence that poor B vitamin status
may be involved. In a study of 195 urban and 216 rural women,
Zhan et al. (1997) reported a correlation between measures of
folate and vitamin B-12 status and the occurrence of NTD in
rural China. Furthermore, a recent folic acid supplementation
trial among nearly 250,000 Chinese women reported that
periconceptional intake of 400 g of folic acid/d reduced the
risk of NTD by as much as 85% in Northern areas and 40% in
Southern regions (Berry et al. 1999).
In addition to birth defects, however, which are relatively
rare events, maternal B vitamin deficiencies may contribute to
more common adverse pregnancy complications, such as spontaneous abortion (Giles 1966, Hibbard 1964, Wouters et al.
TABLE 3
Transferrin receptor (TfR) concentration and percentage of
Chinese women with elevated TfR, stratified by ferritin
concentration
Ferritin
n1
g/L
12
1219.9
2029.9
30
83
58
64
294
TfR2
Elevated TfR
(8.3 mg/L)
mg/L
7.1 3.9
5.4 2.2
4.5 1.8
4.8 2.2
32.53
12.1
4.6
5.5
1 Total n 499.
2 Means SD differ significantly across ferritin strata, P 0.0001
(ANOVA). Mean TfR for ferritin 12 g/L differs significantly from all
other strata, P 0.05 (Tukey).
3 Proportions differ significantly, P 0.0001 (2); P for trend
0.0001 (Mantel-Haenszel).
2707
TABLE 4
Seasonal variations in B vitamin, hemoglobin, ferritin and transferrin receptor (TfR) concentrations among young Chinese women1
Variable
1
2
3
4
5
Spring
Summer
Fall
127
10.2 (9.510.9)a
112
10.7 (10.011.3)a
113
7.9 (7.28.6)b
210
9.8 (9.310.4)a
127
36.0 (32.439.7)b
112
36.0 (32.139.9)b
113
46.5 (42.750.4)a
210
43.2 (40.446.0)a
127
359 (336381)a
112
376 (353400)a
113
357 (333381)a
210
375 (357392)a
126
110.0 (107.8112.3)a
112
109.4 (107.1111.8)a
109
102.3 (100.0104.7)b
210
108.4 (106.7110.2)a
127
40.3 (34.346.2)a
112
38.7 (32.445.0)a
91
43.2 (36.250.2)a
169
46.4 (41.251.5)a
127
5.0 (4.55.4)a
112
5.0 (4.55.4)a
91
5.4 (4.96.0)a
169
5.5 (5.15.9)a
Seasons were defined as follows: winter (Dec/Jan/Feb), spring (Mar/Apr/May), summer (June/July/Aug) and fall (Sept/Oct/Nov).
Total sample size (in parentheses) varies from 563 due to missing values or insufficient plasma for analysis.
CI, confidence interval.
Values with different superscripts in a row differ significantly, P 0.05 (ANOVA with Tukeys studentized range test).
Vitamin B-6 as pyridoxal-5-phosphate.
Winter
RONNENBERG ET AL.
2708
TABLE 5
B vitamin and iron parameters in young Chinese women, stratified by hemoglobin concentration
Hemoglobin concentration
Variable
100
100119
120
P for model1
P for trend2
g/L
111
9.1 3.8b
26.1
332
9.6 4.1a,b
24.4
112
10.4 4.6a
16.1
0.047
0.135
0.075
111
346 120b
12.6
332
368 129a,b
10.8
112
392 131a
4.5
0.025
0.084
0.042
111
36.5 13.8b
35.1
332
39.6 15.6b
26.5
112
45.0 16.7a
14.3
0.001
0.002
0.001
111
39.3 32.7a
22.5
307
42.3 34.1a
16.6
74
49.5 37a
8.1
0.130
0.036
0.011
111
5.9 3.6a
16.2
307
5.1 2.4b
10.8
74
4.8 1.6b
1.4
0.011
0.006
0.002
1 Means compared using ANOVA. Values with different superscripts in a row differ significantly, P 0.05 (Tukey). Proportions compared using
2 analysis.
2 Mantel-Haenszel 2.
3 Sample size varies from 563 due to missing values or insufficient plasma for analysis.
4 Abnormal values defined as folic acid 6.8 nmol/L, vitamin B-12 221 pmol/L, vitamin B-6 30 nmol/L, ferritin 12 g/L and transferrin
receptor (TfR) 8.3 mg/L.
5 Vitamin B-6 as pyridoxal-5-phosphate.
way of more sensitively identifying iron deficiency in conditions in which ferritin concentrations may be altered by factors
other than iron stores, such as gestation (Carmel and Skikne
1992) or inflammation (Ahluwalia 1998). We found that the
prevalence of elevated TfR increased significantly as Hb and
ferritin concentrations decreased, with elevated TfR observed
in a third of women with depleted iron stores. However, of the
53 women with elevated TfR concentrations, only 27 (51%)
had a plasma ferritin concentration of 12 g/L, and 32
(60%) had a ferritin concentration of 16 g/L. This finding
contrasts with those of Carriaga et al. (1991), who reported
that 100% of their subjects with elevated TfR also had ferritin
of 16 g/L. Our results can be interpreted in one of two
ways: either 1) ferritin is pathologically elevated due to infection or inflammation or 2) factors other than iron depletion
are contributing to elevated TfR concentrations. Previous
studies showed that elevated TfR also occurs in conditions
associated with ineffective erythropoiesis, such as thalassemia
(Ahluwalia 1998) and megaloblastic anemia due to vitamin
B-12 deficiency (Carmel and Skikne 1992). We have no data
on the prevalence of thalassemia in our cohort, although
others have reported that some variant of the trait may be
carried by 3% of persons in Southern China (Xu et al. 1996),
so this disorder may be a factor in our study. Severe vitamin
B-12 deficiency (275 pmol/L) was rare in our population,
occurring in just 7 women (1.2%), whereas severe folic acid
deficiency (4.5 nmol/L) was detected in 33 women (6%).
Without other hematologic measures, such as mean cell volume, we cannot determine whether severe B vitamin deficiencies were associated with megaloblastosis.
Although 80% of our study subjects met the World
that such differences were necessarily related to nutrient intake. Nevertheless, it is clear from our data that the women
with low Hb concentrations were also more likely to have
micronutrient deficiencies.
Poor micronutrient status among women of childbearing
age jeopardizes their health and may influence their risk of
achieving a normal pregnancy and delivering a healthy infant.
Although we found a high prevalence of micronutrient deficiencies in Chinese textile workers of reproductive age, most
of these deficiencies could be corrected easily and inexpensively through appropriate supplementation with B vitamins
and iron. Family planning and antenatal care are available to
these women, and the incorporation of nutritional counseling
and therapy into these services could provide a convenient
means of improving both maternal and infant health.
ACKNOWLEDGMENTS
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We want to express our thanks to Marie Nadeau and Irene Ellis for
their technical assistance and to Jacob Selhub, Richard Wood (Tufts
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of Public Health) for their advice and assistance.
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