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Community and International Nutrition

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

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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.

risk of neural tube defects (NTD3) (Czeizel and Dudas 1992,


Mills et al. 1995, Steegers-Theunissen et al. 1994), and other
evidence indicates that vitamin B-12 status also may influence
NTD risk, independent of folate status (Kirke et al. 1993,
Steen et al. 1998). Folate deficiency during pregnancy has
been associated with low birth weight (LBW) and preterm
delivery (Baumslaug et al. 1970, Scholl et al. 1996), and
prenatal vitamin B-6 status may influence birth weight as well
(Kubler 1981). Poor B vitamin status also has been linked to
hyperhomocysteinemia, which is associated with an increased
risk of NTD (Mills et al. 1995, Molloy et al. 1998), preeclampsia (Leeda et al. 1998, Rajkovic et al. 1997) and spontaneous
abortion (Steegers-Theunissen et al. 1992, Wouters et al.
1993).
Iron deficiency remains the most common nutrient deficiency worldwide, with women of childbearing age among
those at the greatest risk (DeMaeyer and Adiels-Tegman
1985). Iron deficiency impairs immune function (IOM 1990)
and was associated with reduced work output among women
cotton mill workers in Beijing, China (Li et al. 1994). Recent
evidence indicates that iron deficiency during pregnancy negatively affects fetal growth (Singla et al. 1997) and increases

Little is known about the micronutrient status of young


women in China. Most Chinese nutrition surveys have involved men and have assessed dietary intake, usually with
respect to energy and protein. Few studies have measured
biochemical indicators of micronutrient status, particularly
among women of childbearing age. According to U.S. data,
however, the highest prevalence of certain micronutrient deficiencies occurs among young women aged 20 44 y (Life
Sciences Research Office 1984), and similar findings have
been reported for women in developing countries (Hercberg
and Galan 1992). The limited data that are available from
China suggest that deficiencies of iron (Li et al. 1993, Zhou et
al. 1998), folic acid (An and Xiu-qing 1986) and other B
vitamins (Zhan et al. 1997) may be relatively common among
young Chinese women.
The recognition of micronutrient deficiencies in women of
reproductive age is important not only because nutritional
status affects the womans health and productivity but also
because deficiencies are associated with adverse pregnancy
outcomes. Poor periconceptional folic acid status increases the

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.

0022-3166/00 $3.00 2000 American Society for Nutritional Sciences.


Manuscript received 10 April 2000. Initial review completed 16 May 2000. Revision accepted 3 August 2000.
2703

RONNENBERG ET AL.

2704

SUBJECTS AND METHODS


Subjects. The current assessment of nutritional status was conducted in conjunction with an on-going prospective study of the
effects of rotating shift work on reproductive outcomes among female
textile workers in Anqing, China. Anqing is located 200 km west
of Shanghai. All employees of the textile mills and their families
receive health care, including prenatal, delivery and postnatal care, in
the nearby hospital. For the present study, eligible subjects were the
563 women enrolled in the shift work study between August 1996
and December 1998. All women were married and between 20 and
34 y of age and had never smoked. In addition, eligible women had

obtained permission to have a child and were attempting to become


pregnant during the course of the prospective study. Women were
excluded if they were pregnant at the initial interview, had tried
unsuccessfully to get pregnant for at least 1 y, were current or former
smokers or planned to quit, change jobs or move out of the city in the
coming year. Although we originally intended to evaluate the effects
of work shift on nutritional status, only 39 women enrolled during
this period worked nonrotating shifts, so data for all types of shifts
were pooled for analyses. The Human Investigations Review Committees at the Harvard School of Public Health and Beijing Medical
University approved all study procedures, and informed consent was
obtained from each woman.
Measurements. At enrollment, height and body weight in light
clothing were measured to the nearest 0.1 kg and 0.1 cm, respectively,
with a beam weighing scale and measuring system. At that time,
interviewers administered a previously validated questionnaire to the
women and their husbands to collect baseline information on sociodemographic, environmental and personal attributes that might be
related to shift work and reproductive outcomes. Included among
these variables were education level, menstrual characteristics (cycle
length and bleeding days/cycle), use of contraceptives or vitamin
and/or mineral supplements and current intake of alcohol.
Preexisting nonfasting blood samples were used for this project.
They were obtained from women before the initial interview via
venipuncture into 10-mL, metal-free EDTA-treated tubes. A small
aliquot of whole blood was used to determine hemoglobin (Hb)
concentration. The remaining blood was centrifuged, and plasma was
obtained and stored at 20C until shipped on dry ice to the Harvard
School of Public Health, where it was stored at 70C before
nutritional analyses. Frozen samples were transported to the U.S.
Department of Agriculture Human Nutrition Research Center on
Aging at Tufts University, Boston, MA, where plasma concentrations
of ferritin, TfR, folic acid and vitamins B-6 and B-12 were measured.
Hb concentration was determined in whole blood according to an
automated colorimetric procedure. Plasma folate and vitamin B-12
concentrations were determined with a radioimmunoassay method
using a commercially available kit from BioRad Diagnotics Group
(Hercules, CA). Plasma vitamin B-6 (as pyridoxal-5-phosphate) was
measured according to the tyrosine decarboxylase apoenzyme method
(Shin et al. 1983). Vitamin measurements were completed in four
batches over an 11-mo period, with 63282 samples in each batch.
Typical coefficients of variation for in-house control plasma samples
were 4.4 7.5% for folate, 5.37.4% for vitamin B-12 and 3.15.8%
for vitamin B-6. Plasma ferritin and TfR concentrations were determined in a subset of 499 women for whom adequate plasma samples
were available with the use of enzyme immunoassays kits from Ramco
Laboratories (Houston, TX). These measurements were made in
three batches during a 13-mo period, with 100 282 samples in each
batch. Mean intra-assay and interassay variabilities were 4.2 and 6.0%
for TfR and 6.7 and 7.7% for ferritin, respectively.
Statistical analysis. We used SAS statistical software for Windows, version 6.12 (SAS Institute 1989) for all analyses. Summary
statistics were calculated and used to describe Hb and plasma concentrations of folic acid, vitamin B-12, vitamin B-6, ferritin and TfR.
Mean (arithmetic) plasma vitamin concentrations were compared
with published reference values to determine the proportion of
women with deficiency. Below normal Hb concentration was defined
as 120 g/L, which is based on World Health Organization recommendations (World Health Organization 1968) for nonpregnant
women. Below-normal concentrations for other nutritional variables
were defined as 12 g/L for ferritin (DeMaeyer 1989), 8.3 mg/L
for TfR (Yeung et al. 1998), 6.8 nmol/L (3 ng/mL) for folic acid
(Herbert and Das 1994), 30 nmol/L for pyridoxal-5-phosphate
(Leklem 1994) and 221 pmol/L (300 pg/mL) for vitamin B-12
(Koehler et al. 1996).
To determine whether micronutrient status was related to age,
body mass index (BMI), education, menstrual characteristics or the
use of contraceptives, we compared mean micronutrient concentrations across categories of these variables using the General Linear
Models (GLM) procedure of SAS Institute and compared the proportion of women with abnormal values across categories using 2
analyses (Selvin 1996). To determine whether micronutrient status

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the risk of infant iron deficiency (Kilbride et al. 1999, Preziosi


et al. 1997), which is associated with lower Apgar scores
(Preziosi et al. 1997) and potentially irreversible delays in
cognitive and psychomotor development (Lozoff et al. 1996).
The identification of iron deficiency can be complicated by
physiologic changes that perturb typical measures of iron status. For instance, although plasma ferritin concentration is the
most sensitive indicator of iron deficiency in healthy persons
(Cook and Skikne 1989), infections and other inflammatory
processes that trigger an acute-phase response can artificially
elevate ferritin concentrations. Previous studies indicate that
the exposure of textile workers to cotton dust initiates both
acute and chronic lung inflammation (Li et al. 1995, Rylander
1987), which could speciously elevate ferritin concentrations,
thereby complicating estimates of iron deficiency in textile
workers. Recently, transferrin receptor (TfR) concentration
was identified as a useful and stable measure of iron status,
reflecting tissue iron availability while remaining unaffected by
infection (Ahluwalia 1998). The determination of both ferritin and TfR may provide a more sensitive and reliable measure of iron status in some groups, including textile workers.
Although micronutrient deficiencies in reproductive-age
women jeopardize both their health and that of their offspring,
intervention trials indicate that supplementation improves
nutritional status (Li et al. 1994, Ubbink et al. 1994) and
reduces the reproductive risks associated with deficiency
(Baumslag et al. 1970, Berry et al. 1999, Czeizel and Dudas
1992, Medical Research Council Vitamin Study Research
Group 1991). In 1992, the U.S. Public Health Service advised
women who were pregnant or were capable of becoming pregnant to consume at least 400 g of folic acid/d (MMWR
1992). No data are available on the prevalence of routine
periconceptional vitamin and mineral supplementation in
China. However, cereal grains in China are not fortified with
folic acid, and a recent folic acid intervention study in China
found that 40 48% of women who had been asked to purchase and consume folate supplements in the perinatal period
did not comply (Berry et al. 1999). Even in large urban areas
such as Beijing, where antenatal care is widely available and
prenatal supplements are routinely recommended, supplementation most likely begins after pregnancy has been clinically
established, usually around weeks 8 10, which is too late to
prevent adverse pregnancy events that occur earlier in gestation, such as spontaneous abortion or certain birth defects.
Thus, suboptimal micronutrient status in young Chinese
women could be an important determinant of adverse pregnancy outcomes that would be amenable to intervention.
The present study in Chinese women of childbearing age
was designed to address the following questions: 1) How prevalent and severe are deficiencies of B vitamins and iron in this
population? 2) Does the prevalence of these deficiencies vary
by season? 3) What is the relation between anemia and plasma
concentrations of ferritin and TfR? 4) What is the relation
between anemia and B vitamin deficiencies?

MICRONUTRIENTS IN YOUNG CHINESE WOMEN

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.

was influenced by the season in which blood samples were obtained,


we defined four seasons as follows: winter (December, January, February), spring (March, April, May), summer (June, July, August) and
fall (September, October, November). Seasons in which mean Hb or
plasma micronutrient concentrations differed significantly were identified using the GLM procedure of SAS Institute with Tukeys adjustment for multiple comparisons (Kleinbaum et al. 1988). In addition, the proportion of women with abnormal values was determined
for each season, and significant differences among the proportions
were evaluated using 2 analyses (Selvin 1996). The GLM procedure
was also used to determine whether mean TfR concentration varied
across strata of ferritin and whether mean vitamin, ferritin and TfR
concentrations varied across Hb strata. In both analyses, significantly
different means were identified using Tukeys adjustment for multiple
comparisons (Kleinbaum et al. 1988). Similarly, the proportion of
women with elevated TfR was compared across ferritin strata and the
proportion of women with abnormal nutritional parameters was compared across strata of Hb, with significant differences among the
proportions evaluated using 2 analyses and the Mantel-Haenszel 2
test for trend (Rosner 1995). If not otherwise noted, statistical significance refers to P 0.05.

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

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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
%

Folic acid, nmol/L


Vitamin B-12, pmol/L
Vitamin B-6, nmol/L3
Hemoglobin, g/L
Ferritin, g/L
TfR, mg/L

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

1 Sample size varies from 563 due to missing values (hemoglobin) or


insufficient plasma for analyses (ferritin and TfR).
2 Abnormal is defined as folic acid 6.8 nmol/L, vitamin B-12 221
pmol/L, vitamin B-6 30 nmol/L, hemoglobin 120 g/L, ferritin 12
g/L and TfR 8.3 mg/L.
3 As pyridoxal-5-phosphate.

RONNENBERG ET AL.

2706

proportion of women with anemia, depleted iron stores or


elevated TfR (2 P 0.05).
Seasonal variations in micronutrient deficiencies and anemia. Mean folic acid and Hb concentrations were significantly lower in summer than in the other seasons, whereas
mean vitamin B-6 concentration was lower in winter and
spring than in summer and fall (Table 4). No seasonal variations were observed in plasma concentrations of vitamin B-12,
ferritin or TfR.
Distinct seasonal trends also were observed in the prevalence of anemia and deficiencies of folic acid and vitamin B-6
(Fig. 2). Folate deficiency was much more common in summer
than in the other seasons (42% versus 20%, 2 P 0.001),
and the prevalence of moderate anemia (Hb 100 g/L) followed the same seasonal pattern as folate deficiency, with
twice as many moderately anemic women observed in summer
as in winter (31% versus 15%, 2 P 0.01). The percentage
of women with mild anemia (Hb 100 120 g/L) remained fairly
constant across the seasons at 60% (data not shown). Vitamin B-6 deficiency occurred in 35% of women in winter and
spring compared with only 15% of women in fall (2 P
0.001).
Relation between micronutrient deficiencies and anemia.
We compared nutritional status across three strata of Hb
concentration: 100, 100 119 and 120 g/L (Table 5).
Mean concentrations of all three vitamins were significantly
lower among women with Hb of 100 g/L than among nonanemic women. Moreover, the prevalence of vitamin deficiencies decreased across Hb strata, with the prevalence of vitamin
B-6 deficiency, for instance, nearly 250% greater among
women in the lowest Hb group than among nonanemic
women. Among women with Hb of 100 g/L, 54% were
deficient in one or more vitamins compared with 31% of
nonanemic women (2 P 0.002). Although the prevalence
of iron depletion (ferritin 12 g/L) was 275% greater among
women in the lowest Hb group than among nonanemic
women, only 18% of all anemic women and 23% of women
with Hb of 100 g/L had depleted iron stores, and only 12%
of anemic women had elevated TfR.
DISCUSSION
In the present study, 44% of Chinese women had evidence
of single or combined B-vitamin deficiencies, nearly 17% had

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FIGURE 1 Distribution of hemoglobin concentration among 557


Chinese women of childbearing age. Sample size varies from 563 due
to missing values for hemoglobin.

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).

MICRONUTRIENTS IN YOUNG CHINESE WOMEN

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.

1993), preeclampsia (Brophy and Siiteri 1975), preterm birth


and LBW (Hibbard 1975, Kubler 1981, Scholl et al. 1996),
and can lead to elevated homocysteine concentrations, which
have been linked to preeclampsia (Rajkovic et al. 1997) and
spontaneous abortion (Wouters et al. 1993). The high prevalence of B vitamin deficiencies that we observed may increase
the risk of adverse pregnancy outcomes. In 1990, the proportion of Chinese infants with LBW was estimated at 59.9%
(World Health Organization 1992). Zhang et al. (1991) reported that from 1986 to 1987, the perinatal mortality rates in
Shanghai were 13 and 15 times higher among LBW and

FIGURE 2 Seasonal variations in the percentage of young Chinese


women with abnormal concentrations of hemoglobin (n 557), folic
acid and vitamin B-6 (n 562). Folate deficiency was defined as folic
acid of 6.8 nmol/L and vitamin B-6 deficiency (as pyridoxal-5-phosphate) of 30 nmol/L. For this figure, abnormal hemoglobin was defined as 100 g/L. Percentages vary significantly across seasons; 2 P
0.001 for folate and vitamin B-6 and P 0.01 for hemoglobin.
Sample sizes vary from 563 due to missing values.

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Folic acid, nmol/L


n (562)2
Means (95% CI)3,4
Vitamin B-6, nmol/L5
n (562)
Means (95% CI)
Vitamin B-12, pmol/L
n (562)
Means (95% CI)
Hemoglobin, g/L
n (557)
Means (95% CI)
Ferritin, g/L
n (499)
Means (95% CI)
TfR, mg/L
n (499)
Means (95% CI)

Winter

preterm infants, respectively, than among infants of normal


weight and gestational age. Correction of maternal vitamin
deficiencies through supplementation could provide an easy
and inexpensive means of reducing perinatal deaths.
In the present study, 17% of women had ferritin concentrations of 12 g/L, and an additional 19% had ferritin
concentrations of 1224 g/L, reflecting low but not yet
depleted iron stores. Although these findings suggest that
nearly 40% of women had some degree of iron depletion, they
may actually underestimate the true prevalence of iron deficiency. Ferritin concentration is pathologically elevated in
response to acute and chronic inflammation (Blake et al. 1981,
Kuvibidila et al. 1994), and Li et al. (1995) reported that
exposure to cotton dust increased airway inflammation in
cotton mill workers in Beijing. Similar increases in inflammatory markers among textile workers have been reported by
others (Keman et al. 1998, Rylander 1987), and it is possible
that the women in our study had artificially elevated ferritin
concentrations due to an inflammatory response related to
textile work. An independent measure of inflammation, such
as C-reactive protein, would be necessary to confirm this
suspicion.
Even if we assume that only 17% of our subjects have iron
deficiency, without supplemental iron their iron status is likely
to deteriorate further, particularly because most will become
pregnant over subsequent months (IOM 1990). In a study of
221 pregnant women in Taipei, Taiwan, Ho et al. (1987)
found that 10% of previously nonanemic, unsupplemented
women developed frank iron deficiency anemia and that 52%
developed some degree of iron deficiency by the end of their
pregnancy. Poor maternal iron status during pregnancy is
associated with reduced infant length and Apgar scores (Preziosi et al. 1997), lower birth weight and mid-arm circumference (Singla et al. 1997) and iron deficiency during infancy
(Kilbride et al. 1999), which is associated with long-term
developmental disadvantages (Lozoff et al. 1991).
Assessment of TfR concentration has been advocated as a

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

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Folic acid, nmol/L


n3
Means SD
% Deficient4
Vitamin B-12, pmol/L
n
Means SD
% Deficient
Vitamin B-6, nmol/L5
n
Means SD
% Deficient
Ferritin, g/L
n
Means SD
% Abnormal
TfR, mg/L
n
Means SD
% Elevated

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

Health Organization (1968) criteria for anemia (Hb 120


g/L), 75% of these had very mild anemia (Hb of 100 119 g/L)
and 20% had Hb of 100 g/L. The high prevalence of mild
anemia is consistent with data from the Chinese Institute of
Nutrition and Food Hygiene (1985), which reported that
2155% of fertile women were anemic. In a study of 447
nonpregnant female cotton mill workers in Beijing, Li et al.
(1993) reported a mean Hb of 123 15 g/L and a 34%
prevalence of anemia. In that study, 71% of anemic women
(24% of their subjects overall) had serum ferritin of 12
g/L, leading the authors to conclude that most of the anemia
in their population was related to iron deficiency. In our study,
the contribution of iron deficiency to anemia appears to be
much smaller. We found that only 18% of all anemic women
and 22% of those with Hb of 100 g/L had depleted iron
stores, whereas 54% of our subjects with Hb of 100 g/L were
deficient in at least one B vitamin. These findings suggest that
in addition to iron deficiency, B vitamin deficiencies are
contributing to the high prevalence of anemia in our population. This conclusion is supported by the similarity in the
seasonal patterns observed for low Hb and folate deficiency,
whereas no seasonal effects were observed for plasma ferritin.
No data were available on the folic acid, vitamin B-6 or
vitamin B-12 status of women in the Beijing study (Li et al.
1993). However, the mean weight and BMI of Anqing women
in the present study were 49.2 kg and 19.8 kg/m2, respectively,
compared with 55.6 kg and 22.1 kg/m2 in the Beijing study.
These anthropometric differences suggest that energy balance
and perhaps overall nutritional status differed between the
Anqing and Beijing textile workers, although without reliable
dietary data for the two groups, it is impossible to conclude

MICRONUTRIENTS IN YOUNG CHINESE WOMEN

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
University), Andrew Damokosh and Walter Willett (Harvard School
of Public Health) for their advice and assistance.

2709

2710

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