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a Center for Human Nutrition, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205 and b International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh 1000
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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1.05 µmol/L or 0.28 µmol/g fat) throughout the
study. Overall, mean maternal serum retinol concentrations were not
affected by supplementation. Compared to the placebo group, the mean
MRDR ratio of 6-mo-old infants was higher in the vitamin A group.
Infants (33%) had serum retinol concentrations <0.70 µmol/L and
88% had MRDR ratios 
0.06. We conclude that while both interventions
were beneficial, neither was sufficient to correct the underlying
subclinical vitamin A deficiency in these women nor to bring their
infants into adequate vitamin A status.
KEY WORDS: • humans • lactation • vitamin A • ß-carotene • supplementation
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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, Humphrey et al. 1992
, Katz et al. 1995
, Underwood 1994
). In recent years, efforts to develop interventions for
these population groups have increased. One effective strategy for
simultaneously improving the vitamin A status of lactating women and
their breastfeeding infants is maternal vitamin A supplementation
during the postpartum period. The World Health Organization (WHO)
supports this approach and currently recommends that all lactating
women living in endemic areas of vitamin A deficiency should be given
one dose of 200,000 international units (IU) [60,000 retinol
equivalents (RE)]6vitamin A within 8 wk postpartum. WHO also recommends that
supplementation take place as soon as possible after delivery in order
to maximize the benefits on maternal vitamin A status, breast-milk
vitamin A concentrations and subsequent infant vitamin A status
(WHO/UNICEF/IVACG task force 1997
).
Previous randomized studies demonstrated the biological efficacy of
maternal vitamin A supplementation. In a placebo-controlled trial in
Indonesia, a 300,000-IU (90,000 RE) dose administered at 1–3 wk
postpartum resulted in improvements in maternal vitamin A status, the
vitamin A content of breast milk and infant vitamin A status
(Stoltzfus et al. 1993
). Similar findings were reported
from a trial in Thailand in which a 300,000-IU (90,000 RE) dose was
given within 3 d of delivery (Thanangkul et al. 1974
). In Bangladesh, a 200,000-IU (60,000 RE) dose given at
delivery also resulted in improvements in maternal vitamin A status and
breast-milk vitamin A concentrations, but infant status was not
assessed (Roy et al. 1997
). In addition, in a
nonrandomized study in Bangladesh, a 300,000-IU (90,000 RE) dose given
within 3 mo postpartum was found to have a positive impact on infant
mortality (de Francisco et al. 1995
).
An alternative strategy for improving the vitamin A status of young
infants is to supplement them directly, either at birth or during other
contacts with the health-care system. In Bangladesh, infants who
received immunizations and vitamin A during Expanded Program on
Immunization contacts had increased serum retinol concentrations when
compared to those who received immunizations and placebos
(Mahalanabis et al. 1997
, Rahman et al. 1995
). However, 10–15% of the infants in these studies
developed bulging fontanelle shortly after dosing (Baqui et al. 1995
, de Francisco et al. 1993
). While the
condition was transient and there appears to be no long-term side
effects associated with this phenomenon (van Dillen et al. 1996
), concerns about this approach to infant dosing remain. In
a safety study conducted in Indonesia, a 50,000-IU (15,000 RE) dose of
vitamin A given to infants at birth was associated with a 2% excess
rate of bulging fontanelle, but this condition was not associated with
an increase in intracranial pressure or with increased rates of any
other sign or symptom of morbidity (Agoestina et al. 1994
). However, utilizing maternal supplementation programs to
deliver vitamin A to young infants would prevent this potential
problem, as well as benefit mothers.
In contrast to supplementation programs, food-based interventions are
promoted as a more sustainable and long-term solution for the problem
of vitamin A deficiency. Most food-based programs attempt to increase
the consumption of low-cost ß-carotene-rich fruits and vegetables,
since foods containing preformed vitamin A are generally more
expensive. However, very little data exist on the efficacy of
ß-carotene interventions for improving the vitamin A status of
lactating women. While observational studies suggest that women with
higher dietary ß-carotene intakes produce breast milk with higher
vitamin A content (Newman 1993
), a recently conducted
placebo-controlled trial in Indonesia found that maternal vitamin A
status and breast-milk vitamin A concentrations increased in response
to ß-carotene consumed as synthetic supplements, but not to
ß-carotene in vegetables (de Pee et al. 1995
). A
variety of factors affect the efficiency with which increased
ß-carotene intakes from fruits and vegetables can improve vitamin A
status (de Pee and West 1996
), and further research is
needed to determine the efficacy of ß-carotene interventions for
improving the vitamin A status of lactating women.
To investigate the efficacy of both maternal vitamin A supplementation as currently recommended by WHO and daily, dietary level synthetic ß-carotene supplementation, we conducted a community-based, individually randomized, placebo-controlled trial among lactating women in Matlab, Bangladesh. In this report we describe the main effects of maternal postpartum supplementation on subsequent maternal and infant vitamin A status.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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This study was conducted in the 70 villages of the International Centre
for Diarrhoeal Disease Research Centre for Health and Population
Research (ICDDR,B) Maternal Child Health Family Planning Project
(MCH-FP project) intervention area located 45 km southeast of the
capital city of Dhaka in the Matlab thana of rural Bangladesh. Rice,
jute and fish are the main agricultural products of this river delta
region. ICDDR,B has maintained demographic surveillance of the
population since the 1960s and over the years has provided preventive
and curative health services in the community in conjunction with
ongoing health research projects (Fauveau 1994
).
The existing network of 80 MCH-FP community health workers and logistical support services was utilized for birth detection, capsule delivery, compliance monitoring and motivational activities during the supplementation study. The MCH-FP community health workers routinely visit all households with a married woman of childbearing age twice a month and provide family-planning services, immunizations and treatment or referral to an ICDDR,B clinic for a variety of health problems. Women participating in the supplementation study received these services as usual. The additional study-specific visits at 2 wk, 3, 6 and 9 mo postpartum were conducted by a separate team of trained field workers.
All women registered in the MCH-FP area who delivered a live infant in the service area between June 14–August 29, 1994, were eligible for the trial. After the report of a live birth was received, an enrollment visit was scheduled while infants were in the eligible age range of 7–21 d. Data collected from the MCH-FP records indicated that 368 women delivered live infants during the enrollment period. Women (300) remained eligible for the trial after excluding those who delivered their infants outside of the service area (n = 25), those with infants >21 d-old (n = 35), those whose infants had died (n = 5) and those with severely ill infants (n = 3). Of the 300 eligible families, 48 (16%) refused to participate, and 32 births (11%) were not detected due to the absence of community health workers, a time lag in birth reporting or for other unknown reasons. We successfully recruited 220 (73%) of the eligible women into the study, 218 with single and 2 with twin births.
This study was approved by The Johns Hopkins University School of Hygiene and Public Health Committee on Human Research and the Ethical Review Committee at ICDDR,B. Informed consent was obtained from all study participants in accordance with guidelines at The Johns Hopkins University and ICDDR,B.
Randomization.
The trial was individually randomized and double-blinded. Because the cultural practices in the region prohibit some women from leaving their homes during the first few weeks postpartum, women were given a choice of completing the enrollment visit at 2 wk (±1 week) postpartum either at the central Matlab clinic or in their homes. During the enrollment visit, they were assigned a study identification number that randomly allocated them to one of three treatment groups and to a follow-up schedule that determined the location of their follow-up visits at 3, 6 and 9 mo postpartum. During clinic visits, women provided a full milk sample and a blood sample. During home visits, women provided a casual milk sample, but no blood sample (details described below).
Before beginning the study, individual treatment codes and follow-up
schedules were assigned to a sequence of identification numbers in
blocks of 18 using a random number table (Smith and Morrow
1991
). Each block contained all possible combinations of three
treatment groups (vitamin A, ß-carotene or placebo) and six follow-up
schedules. The six follow-up schedules assigned women to complete
clinic visits at either 0.5 and 3, 0.5 and 6, 0.5 and 9, 3 and 6, 3 and
9 or 6 and 9 mo postpartum. When they were not assigned to a clinic
visit, the women completed their follow-up visits at home. At each
visit, half of the women in each of the three treatment groups
completed a home visit and the other half completed a clinic visit.
Supplementation.
At enrollment, women in the vitamin A group received one 200,000-IU
(60,000 RE) dose of retinyl palmitate while women in the ß-carotene
and placebo groups received placebos. After that, all women took daily
capsules until 9 mo postpartum. Women in the ß-carotene group
received capsules containing 7.8 mg of ß-carotene, and women in the
vitamin A and placebo groups received placebos. Using a conversion
factor of 6 µg of all-trans-ß-carotene: 1 RE, the ß-carotene dose
was designed to approximate one U.S. recommended dietary allowance of
vitamin A for lactating women in the first 6 mo postpartum
[National Research Council (U.S.) Subcommittee on the Tenth Edition of the RDAs 1989
].
The study capsules were manufactured by Tischon Corporation (Salisbury, MD) and delivered to the field and to study participants coded as type A, B or C. Except for the enrollment capsules, which were distributed individually, the capsules were packaged in groups of 18 in blister pack strips. Although the vitamin A and placebo capsules used at enrollment differed slightly in color, they were individually wrapped in foil before distribution, making direct comparisons between the treatment groups unlikely. The ß-carotene and placebo capsules distributed in blister packs were maroon-colored and identical in outward appearance.
At the enrollment visit, women consumed their first capsule under the supervision of a field worker. They were then given one pack of capsules with instructions to take one capsule every morning with their first meal of the day. Over the next 8 mo, the MCH-FP community health workers supplied all study participants with a new pack of capsules every 2 wk. Compliance was monitored through counts from returned capsule packs and spot checks in the field.
Data collection.
Serum retinol and the modified relative dose-response test.
On days of clinic visits, women came to the central Matlab clinic and
received an oral dose of 3,4-didehydroretinyl acetate (8.8 µmol) for
the determination of their MRDR ratio (Tanumihardjo et al. 1996
). This was immediately followed by a high-fat cookie and
tea with lemon. During the waiting period, women were given other
snacks low in vitamin A. A blood sample was collected from the
antecubital vein 5 h after dosing.
At the 6-mo visit, infants were given an oral dose of
3,4-didehydroretinyl acetate (5.3 µmol) for the determination of
their MRDR ratio (Tanumihardjo et al. 1996
). Mothers
were encouraged to breast feed their infants immediately after dosing
and on demand throughout the waiting period. A blood sample was
collected from the femoral vein 5 h after dosing.
After collection, the blood samples were slowly expressed into a foil-covered 8-mL glass vial, allowed to clot in the dark at room temperature for ~1 h and then centrifuged. Serum (500 µL aliquots) was stored at -20°C for up to 3 mo at the field site, transported to Dhaka on ice, stored at -70°C, then transported in liquid nitrogen to Baltimore, MD, and stored at -70°C until analysis.
Serum retinol and didehydroretinol concentrations were assayed at The Johns Hopkins University using reversed-phase high performance liquid chromatography (HPLC). Thawed serum (400 µL) was combined with 75 µL of internal standard [retinyl acetate (Sigma Chemical Co., St. Louis, MO) dissolved in ethanol] and 400 µL of ethanol. This mixture was extracted twice with 750 µL of hexane. The hexane layers were then pooled and evaporated completely under nitrogen.
The residue was redissolved in 50 µL of methanol/dichloromethane (4:1, v/v), and 30 µL was injected onto an equilibrated HPLC system by a Waters WISP 710B autosampler (Waters Corp., Milford, MA). A System Gold Beckman Programmable Detector Module 166 (Beckman Instruments, Inc., Columbia, MD) monitored the wavelength at 350 nm. A System Gold Beckman pump with a 110B Solvent Delivery Module (Beckman Instruments, Inc.) delivered the methanol/water (90:10, v/v) mobile phase at a flow rate of 1.0 mL/min for 8 min and then at 1.5 mL/min until 14 min to the Waters Spherical C18 Resolve 15-cm reversed-phase column (Waters Corp.). Peak areas were integrated by the System Gold software (Version 8.0) which also functioned as the system controller. The didehydroretinol and retinol concentrations were determined in ng/mL from standard curves established in the laboratory.
Quality control was monitored using vitamin A reference materials from the National Institute of Standards and Technology (Gaithersburg, MD). Serum obtained from well-nourished adults who had been dosed with 3,4-didehydroretinyl acetate (8.8 µmol) was used to construct a set of quality-control samples. Day-to-day assay performance was assessed by analyzing 1–3 of these quality-control samples along with each batch of study samples. Over the sample analysis period, the within-run and between-run coefficient of variation for the quality-control samples were 4 and 5% for retinol and 5 and 6% for the molar 3,4-didehydroretinol/retinol (MRDR) ratio, respectively.
The serum retinol values were converted from ng/mL to µmol/L for data
analysis. In infants, serum retinol concentrations <0.70 µmol/L were
used to define low vitamin A status. In both women and infants, an MRDR
ratio 0.06 was considered indicative of marginal vitamin A status
(WHO 1996
).
Breast milk vitamin A and fat content.
Milk samples were collected from all women at each visit. Samples were
collected using two different techniques: "full" collection during
clinic visits, or "casual" collection during home visits. For full
collection, a trained field worker used a manual breast pump (White
River, Laguna, CA) to express the entire contents of one breast which
had not been used to feed an infant for 2 h. Milk was collected from
the left breast except when a breast infection was present or if milk
production had stopped. Samples were collected between 1030 and
2115 h with a median collection time of 1145 h. The
late-night milk collections occurred when evening clinic visits were
scheduled for a few Muslim women in order to accommodate the
traditional dawn-to-dusk fasting period associated with Ramadan.
For casual milk collection, mothers manually expressed ~5 mL of milk into a glass collection jar without control over the time since last breastfeeding episode. A milk sample was collected from the breast which had not been used to feed the infant for the longer period of time or rarely from the only breast capable of producing milk. Casual milk samples were collected between 0800–1900 h with a median collection time of 1050 h.
All milk samples were stored in a cooler on ice and protected from
light until processing later the same day. For processing, the milk
samples were warmed to room temperature and homogenized by gentle
swirling. The fat content of each milk sample was determined in
triplicate using the creamatocrit method (Lucas et al. 1978
). The equation published by Lucas (1978)
was used to convert the volume measurement to grams of milk fat per
liter of milk. Milk (500 µL aliquots) was stored at -20°C for up
to 3 mo at the field site, transported on ice to Dhaka and then stored
at -70°C until analysis.
Milk samples were analyzed at ICDDR,B using reversed-phase HPLC. Milk (400 µL aliquots) was thawed, combined with 200 µL of a pyrogallol in methanol solution (100 g/L), 400 µL of internal standard (ß-apo-8'-carotenal-methyl-oxime) and 1.0 mL of a 5.35 mol/L solution of potassium hydroxide in a methanol/water mixture (80:20, v/v). The samples were saponified at 4°C for 16–20 h. Following the addition of 2.0 mL of saturated sodium chloride solution, the sample was extracted twice with a hexane/ether (80:20, v/v) mixture, cleaned with water and sodium sulfate, dried under nitrogen and reconstituted with 200 µL of mobile phase. The mobile phase consisted of acetonitrile, dichloromethane, ammonium acetate in water (10 g/L) and triethylamine in a ratio of 89:10:1:0.1 (v/v/v/v). Of the reconstituted sample, 25 µL was injected onto an equilibrated HPLC system with a 5-µm YMC-Pack ODS-AL column (YMC, Wilmington, NC). Retinol and internal standard peaks were detected at 325 and 450 nm, respectively. Day-to-day assay performance was monitored by analyzing two quality-control samples with each batch of study samples. The within- and between-run coefficient of variation for the milk vitamin A content of the quality-control samples were 3 and 6%, respectively.
The vitamin A content of milk was calculated as concentration per
volume (µmol/L) and per gram of milk fat (µmol/g). The latter value
was obtained by dividing the vitamin A concentration per volume
(µmol/L) by the fat concentration (g/L) to obtain µmol/g. According
to WHO criteria, values 1.05 µmol/L and 0.28 µmol/g of fat were
considered low (WHO 1996
). In the present report, values
obtained from casual and full milk samples were combined because
analyses of the differences between treatment groups revealed that both
of the milk sampling methods yielded similar conclusions about the
effects of supplementation.
Anthropometric data. Women and infants were weighed to the nearest 0.1 kg at each visit using a digital scale model 770 (Seca Corp., Columbia, MD). Scales were standardized on a daily basis using a 1-kg weight. The women were weighed wearing lightweight clothing. Infants wearing minimal clothing were weighed while in their mother's arms, and their weight was obtained by subtracting the mother's weight alone. Maternal height was measured at the 6-mo visit using a locally constructed height measuring device. Maternal body mass index at baseline was calculated as weight (kg)/height (m)2 using the weight at 0.5 mo and height at 6 mo postpartum.
Infant dietary assessment.
At the 3-, 6- and 9-mo visits, mothers were interviewed about their
infants' dietary intake using 24-h recall interviews and open-ended
food-frequency questionnaires. Complementary feeding was assessed from
the 24-h recall data and defined as giving any type of food or liquid
(other than water or breast milk) in any amount to the infants. The
vitamin A and ß-carotene content of individual foods was assigned
using food tables from Bangladesh (Darnton-Hill et al. 1988
), and those containing >100 RE/100 g were considered
vitamin A-rich foods. At the 6-mo visit, mothers were presented with a
selection of locally available infant vitamin syrups and asked to
identify the amount and type of any supplemental vitamins their infants
had been given.
Demographic and socio-economic data. Baseline data on maternal age, educational level and religious affiliation were obtained from the existing MCH-FP database for all women in the area who delivered live infants during the recruitment period. Data on the total number of reported pregnancies were also obtained for the women enrolled in the study.
Statistical analysis.
The sample size for the study was calculated to detect a difference in
the proportion of individuals with low vitamin A status between a group
who received active supplements (either vitamin A or ß-carotene) and
the placebo group who did not. Therefore, the data were analyzed by
comparing separately the values in the vitamin A to the placebo group
and the values in the ß-carotene to the placebo group. For
categorical variables, comparisons were made using 
2
analyses. For continuous variables, comparisons were made using
two-sided t tests. Because the MRDR ratios were skewed to
high values, the data were log transformed to normalize distributions
prior to statistical testing, and geometric means are reported.
Although P values <0.05 are considered as statistically
significant, values 0.10 are reported to indicate potentially
important trends in the data. Statistical analyses were conducted using
SPSS 7.5 (SPSS Inc., Chicago, IL).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The baseline characteristics of the 220 women and their infants who participated in the study are shown by treatment group in Table 1. The three groups did not differ in maternal age, gravidity, educational level, religious affiliation or body mass index. Infant weights were also similar at enrollment.
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Compliance with supplementation and follow-up rates.
Compliance with daily capsule consumption and the completion of
follow-up visits was high. Twenty-three different women missed one or
more visits resulting in overall follow-up rates of 98, 95 and 92% at
3, 6 and 9 mo, respectively. Among women who completed follow-up
visits, the mean compliance rate with daily capsule consumption was
95%. In order to deliver the intended intervention, regular capsule
consumption was most critical in the ß-carotene group and was
consistently high. Because the first capsule was administered under
supervision, women in the vitamin A group received the full-intended
amount of supplemental vitamin A regardless of subsequent compliance.
Infant dietary intake.
The pattern of complementary feeding, consumption of vitamin A-rich foods and infant vitamin syrups in 6-mo-old infants was comparable between treatment groups (Table 2 ).At 6 mo, all of the infants were still breastfeeding, and although 91% were also receiving complementary foods, these were foods generally low in vitamin A content. According to the food frequency data, only 33% of 6-mo-old-infants had ever been fed a vitamin A-rich food in any amount during their life. Although the practice was not recommended by study staff, 15% of the infants (n = 32) had been given supplemental infant vitamin syrups. In 27 of these cases, the mothers reported syrup brands known to contain vitamin A. The estimated vitamin A intake from these syrups ranged from 22,500 to 210,000 IU with a median of 90,000 IU. In the other cases, brand information was not reported (n = 4) or the syrup given did not contain vitamin A (n = 1).
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Maternal modified relative dose-response ratios and serum retinol
concentrations.
Compared to the placebo group, vitamin A supplementation resulted in
significantly improved vitamin A stores in women at 3 mo postpartum,
evident by a lower proportion of women with an MRDR ratio 0.06
(P < 0.01) and a lower mean MRDR ratio
(P < 0.05) in the vitamin A group (Table 3
).The vitamin A-supplemented women continued to have better vitamin A
status at 6 and 9 mo as assessed by the MRDR test, but the impact of
supplementation was less than that observed at 3 mo.
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0.06) was twice as high. However, this trend was
reversed at subsequent time points. At 6 mo the mean MRDR ratio of
women in the ß-carotene group was lower (P < 0.05)
than the placebo group. In the subset of women assessed at 2 wk and 9 mo postpartum, the mean MRDR ratio (95% confidence interval) in the ß-carotene group (n = 12) was 0.067 (0.044–0.102) at 2 wk and 0.043 (0.029–0.063) at 9 mo. The values for the placebo group (n = 12) at these time points were 0.033 (0.024–0.046) and 0.049 (0.031–0.077), respectively. At 2 wk women in the ß-carotene group had higher (P < 0.05) ratios (i.e., worse liver vitamin A stores) than women in the placebo group. However, when compared to the placebo group, the change in MRDR ratios indicated an improvement (P < 0.01) over time in the liver vitamin A stores of women in the ß-carotene group.
In contrast, neither ß-carotene nor vitamin A supplementation
affected the mean maternal serum retinol concentrations (Table 4
).However, mean concentrations were close to 1.40 µmol/L throughout the
study, and low values were infrequent. Out of the 412 serum samples
from the 220 women, only 1.5% were <0.70 µmol/L and 18.9% were
<1.05 µmol/L. In U.S. adults, serum concentrations 1.05 µmol/L
are considered indicative of adequate vitamin A status (Pilch 1987
). A similar cutoff has not been established for
populations in developing countries.
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Breast milk vitamin A. The vitamin A concentration of breast milk, expressed both as vitamin A per volume and vitamin A per gram of fat, is shown by treatment group in Table 5. At baseline, the vitamin A concentration of milk was not statistically different between the three groups. As expected, milk vitamin A content was highest in transitional milk (0.5 mo) and lower thereafter.
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Infant serum retinol concentrations and modified relative dose-response ratios. The infant serum retinol concentrations and MRDR ratios from 6-mo-old infants are shown in Table 6. The mean serum retinol concentration in the vitamin A group was higher than in the placebo group (P < 0.06). The overall proportion of infants with serum retinol levels <0.70 µmol/L was 33%. This proportion was lowest in the vitamin A group and higher in the placebo and ß-carotene groups. The serum retinol concentration (means ± SD) was not significantly different between infants who were given supplemental vitamin syrups known to contain vitamin A (n = 27) as compared to those (n = 181) who were not (0.82 ± 0.23 µmol/L vs. 0.80 ± 0.22 µmol/L).
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|
DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Other investigators (Roy et al. 1997
, Stoltzfus et al. 1993
, Thanangkul et al. 1974
) also
reported that a single postpartum dose of 200,000–300,000 IU
(60,000–90,000 RE) vitamin A improved maternal vitamin A status and
increased breast-milk vitamin A concentrations. In the present study,
the benefits of a 200,000-IU (60,000 RE) dose of vitamin A were
short-lived. At 9 mo postpartum, more women in both the vitamin A and
placebo groups had lower liver stores than when the study began. This
suggests that the 200,000-IU (60,000 RE) dose of vitamin A was
insufficient to protect women's liver stores from being depleted as a
result of lactation.
Similar to a recent study conducted in Indonesia (de Pee et al. 1995
), we found that daily, dietary level synthetic
ß-carotene supplements improved maternal vitamin A status. While the
proportion of women in the placebo group with low liver stores
increased from 14 to 42% from the beginning to the end of the study,
the proportion in the ß-carotene group remained nearly the same (26
and 31%). This suggests that the daily ß-carotene dose was able to
prevent the depletion of liver stores over time, but not to correct the
underlying deficiency. By chance, women in the ß-carotene group
started the study with poorer vitamin A status than the placebo group.
This may have caused the impact of ß-carotene supplementation to be
underestimated in this study.
At baseline, serum retinol concentrations averaged ~1.70 µmol/L,
which may explain the fact that mean serum retinol did not increase
with either type of supplementation. Serum retinol concentrations are
homeostatically controlled over a wide range of total body stores, and
as vitamin A status improves, serum retinol becomes less responsive to
interventions (Olson 1984
). However, at 9 mo postpartum
significantly fewer women in the ß-carotene group had values <1.40
µmol/L than in the placebo group. Thus, ß-carotene supplementation
was effective in improving the serum retinol concentrations of women
with the lowest initial vitamin A status.
Breast-milk vitamin A concentrations responded quickly to vitamin A
supplementation and more slowly to ß-carotene supplementation.
Previous studies of vitamin A supplementation found a more prolonged
impact on breast-milk vitamin A concentrations. In Indonesia
(Stoltzfus et al. 1993
) and Thailand (Thanangkul et al. 1974
), a higher dose of vitamin A [300,000 IU (60,000
RE)] was effective in maintaining higher breast-milk vitamin A
concentrations among supplemented women for 8 and 9 mo, respectively.
In urban Bangladeshi women who received a 200,000-IU (60,000 RE) dose
at delivery, significantly higher breast-milk vitamin A concentrations
were observed at 6 mo postpartum (Roy et al. 1997
). In
the present study, women receiving ß-carotene supplements produced
breast milk with increasingly higher vitamin A concentrations from 3 to
9 mo, but the concentration was significantly different from the
placebo group only at 9 mo.
Similar to other investigators working in Bangladesh, we found that
breast milk was the most important dietary source of vitamin A for
infants (Brown et al. 1982
, Zeitlin et al. 1992
). In Bangladesh nearly all infants are exclusively breast
fed during the first few months of life, and some continue partial
breastfeeding past 2 y of age (Huffman et al. 1980
). Although nearly all 6-mo-old infants received
complementary foods in the present study, these were foods low in
vitamin A. A low proportion of infants (13%) consumed additional
vitamin A from supplemental vitamin syrups. However, at 6 mo the status
of these infants was similar to the rest of the infants in the study.
We attribute the observed improvements in infant vitamin A status to
increased breast-milk vitamin A concentrations.
Infant vitamin A status followed the trends in breast-milk vitamin A
concentrations prior to 6 mo postpartum. The best status was observed
among infants in the vitamin A group, followed by those in the
ß-carotene and placebo groups. Previous epidemiological studies and
empirical calculations suggest that while breast-milk vitamin A levels
in the range observed in this study (~1 µmol/L) are sufficient to
meet basal needs and avoid clinical deficiency among infants less than
6-mo-old, they are inadequate to build up significant liver reserves of
vitamin A (Underwood 1994
). Our data support these
observations. We found that although liver stores were improved, 85%
of the infants of supplemented mothers still had MRDR ratios indicative
of low liver stores.
Other recent studies in Bangladesh found high proportions of infants
with subclinical vitamin A deficiency. Of 40 apparently healthy
breast-fed infants 5–7 mo of age, 75% had relative dose-response
values indicative of marginal vitamin A status, and 60% had serum
retinol concentrations <0.70 µmol/L (Wahed et al. 1997
). In another study, 56% of the breast-fed infants who had
received up to three doses of 50,000 IU (15,000 RE) vitamin A still had
serum retinol concentrations <0.70 µmol/L at 25 wk of age
(Mahalanabis et al. 1997
).
In spite of the beneficial effects of maternal supplementation,
subclinical vitamin A deficiency remained prevalent in this population.
The prevalence of subclinical deficiency among individuals in the
supplemented groups ranged from 25% using maternal MRDR ratios to 75%
using low breast-milk vitamin A content, to 85% using infant MRDR
ratios. Because these indicators measure different biological
processes, the estimates differ. However, the pattern is consistent,
and the problem would be classified as moderate-to-severe using any of
these indicators according to WHO guidelines (WHO 1996
).
Issues with ß-carotene supplementation.
The conversion of ß-carotene to vitamin A is affected by a wide
variety of factors. Absorption and conversion are unfavorably
influenced by low levels of dietary fat, the presence of infections,
fevers and parasitic infestation (Burri 1997
). We did
not measure or control the amount of dietary fat consumed along with
the ß-carotene supplements. Taking the capsules with a high-fat meal
might have enhanced the absorption of ß-carotene and improved the
response to the intervention.
Helminth infections have been shown to adversely affect the absorption
of nutrients in children (Jalal 1991
) and may have
decreased ß-carotene absorption among the women in this study.
Although population-based studies of helminth infections in Matlab have
not been conducted, a clinic-based study of individuals seeking
treatment for diarrhea found that in 20–49-y-old women, 69% were
infected with Ascaris lumbricoides, 31% with
Trichuris trichiura and 33% with hookworms (Hossain et al. 1981
). Women were not treated for helminth infections as
part of this study protocol. At 9 mo postpartum, 25% reported they had
taken some kind of medication in the past year to treat kirmi (the
local term for worms). Systematically treating women for helminth
infections might have improved their response to the ß-carotene
supplementation.
The ß-carotene supplementation might have affected serum and
breast-milk ß-carotene concentrations, but this was not measured in
the present study. In Indonesia, synthetic ß-carotene supplements
given to lactating women resulted in increased serum ß-carotene
concentrations (de Pee et al. 1995
). Data from a recent
trial conducted in Nepal in which women of reproductive age received
weekly supplements of synthetic ß-carotene or vitamin A also suggest
that ß-carotene may have positive impacts on maternal health aside
from those attributed to its provitamin A activity (West, Jr. et
al. 1997
). Thus, although ß-carotene acted more slowly than
vitamin A to improve maternal and infant vitamin A status in the
present study, it might have had other positive effects that were not
measured.
Vitamin A postpartum dosage levels.
The currently recommended 200,000-IU (60,000 RE) postpartum dose of
vitamin A should allow a healthy woman to maintain her liver reserves
while producing breast milk with normal vitamin A concentrations for
60 d. This calculation assumes: good initial vitamin A status;
good health; dietary intake adequate to meet basal needs for vitamin A;
additional requirement of 500 RE/day due to lactation [National Research Council (U.S.) Subcommittee on the Tenth Edition of the RDAs 1989
]; 50% retention of the supplemental dose (Kusin et al. 1974
, Pereira and Begum 1973
) and 100%
utilization of the retained dose for breast-milk production. Few, if
any, of these assumptions are met by women in developing countries. In
these settings women often have inadequate dietary intakes of vitamin
A, and subclinical deficiency is common. Supplemental vitamin A given
to subclinically deficient women may be utilized first for maternal
needs, rather than for breast-milk production. Thus, the amount of
vitamin A from a single 200,000-IU (60,000 RE) dose that remains
available for transfer into breast milk may be much less than is
required to produce milk with even moderate levels of vitamin A for
more than 1–2 mo.
We conclude that, as a long-term strategy, ß-carotene supplementation
is efficacious for improving the vitamin A status of lactating women.
To benefit breastfeeding infants by 6 mo of age, maternal ß-carotene
supplementation needs to begin during pregnancy or earlier. Our data
suggest that including ß-carotene in prenatal supplements could
increase breast-milk vitamin A concentrations and subsequent infant
vitamin A status. Because previous studies suggest that synthetic
supplements tend to overestimate the impact of food-based interventions
(de Pee and West 1996
), we recommend that dietary
interventions which aim to improve breast-milk vitamin A concentrations
by increasing maternal intakes of ß-carotene should be directed
toward pregnant as well as lactating women or to all women of
reproductive age.
We also conclude that among populations where subclinical vitamin A
deficiency is prevalent, the currently recommended postpartum dose of
200,000-IU (60,000 RE) vitamin A for lactating women is simply not
enough. In this study, a single 200,000-IU (60,000 RE) dose did not
completely correct the subclinical vitamin A deficiency found among
women at the beginning of lactation. During lactation, the dose did not
maintain maternal vitamin A status for more than a few months or
improve breast-milk vitamin A concentrations to levels capable of
building adequate liver vitamin A stores in their 6-mo-old
breastfeeding infants. Previous studies using larger doses demonstrated
a larger and more prolonged impact of supplementation on maternal and
infant vitamin A status with no evidence of adverse effects. The
current recommendation should be reviewed and a higher dosage
considered. A combination program to provide postpartum vitamin A
supplements and prenatal or continuing supplements that contain
ß-carotene may also be feasible in some settings. In addition,
improving dietary vitamin A intakes among all women of reproductive age
should be a priority public-health measure. Years of experience with
vitamin A supplementation programs for preschool age children clearly
teach us that supplementation programs alone cannot completely solve
the problem of vitamin A deficiency (UNICEF 1998
).
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
1 Presented in part at Experimental Biology 98 in
San Francisco, April 20, 1998. A. L. Rice, R. J. Stoltzfus,
A. de Francisco, J. Chakraborty, C. L. Kjolhede, and M. A. Wahed. Maternal vitamin A or ß-carotene supplementation in
lactating Bangladeshi women: effects on mothers and infants. FASEB
1998;12:A648.
2 Supported by cooperative agreements
between The Johns Hopkins University School of Hygiene and Public
Health, Baltimore, MD, USA and the Office of Health and Nutrition, U.S.
Agency for International Development, Washington, DC
(DAN-5116-1-00-8051-00 and HRN-A-00-97-00015-00). The study was a
collaborative project between the Johns Hopkins University and the
International Centre for Diarrhoeal Disease Research, Bangladesh
(ICDDR,B). The ICDDR,B is supported by the aid agencies of the
governments of Australia, Bangladesh, Belgium, Canada, Japan, The
Netherlands, Norway, Saudi Arabia, Sri Lanka, Sweden, Switzerland, the
United Kingdom and the United States; international organizations
including Arab Gulf Fund, European Union, the United Nations
Children's Fund (UNICEF), the United Nations Development Programme
(UNDP), and the World Health Organization (WHO); private foundations
including Aga Khan Foundation, Child Health Foundation (CHF), Ford
Foundation, Population Council, Rockefeller Foundation, Thrasher
Research Foundation and the George Mason Foundation; and private
organizations including East West Center, Helen Keller International,
International Atomic Energy Agency, International Center for Research
on Women, International Development Research Center, International Life
Sciences Institute, Karolinska Institute, London School of Hygiene and
Tropical Medicine, Lederle Praxis, National Institutes of Health (NIH),
New England Medical Center, Procter & Gamble, RAND Corporation, Social
Development Center of Philippines, Swiss Red Cross, the Johns Hopkins
University, the University of Alabama at Birmingham, the University of
Iowa, University of Goteborg, UCB Osmotics Ltd., Wander A. G. and
others.
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 Research Institute, The Mary Imogene
Bassett Hospital, Cooperstown, NY 13326.
5 Abbreviations used: HPLC, high performance
liquid chromatography; ICDDR,B, International Centre for Diarrhoeal
Disease Research, Bangladesh; IU, international unit; MCH-FP project,
Maternal Child Health-Family Planning project; MRDR ratio, modified
relative dose-response ratio; RE, retinol equivalent; WHO, World Health
Organization.
Manuscript received May 21, 1998. Initial review completed July 14, 1998. Revision accepted November 2, 1998.
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
1. Agoestina T., Humphrey J. H., Taylor G. A., Usman A., Subardja D., Hidayat S., Nurachim M., Wu L., Friedman D. S., West K. P., Jr. Safety of one 52-µmol (50,000 IU) oral dose of vitamin A administered to neonates. Bull. WHO 1994;72:859-868.[Medline]
2. Baqui A. H., de Francisco A., Arifeen S. E., Siddique A. K., Sack R. B.. Bulging fontanelle after supplementation with 25,000 IU of vitamin A in infancy using immunization contacts. Acta Paediatrica 1995;84:863-866.[Medline]
3.
Brown K. H., Black R. E., Becker S., Nahar S., Sawyer J.. Consumption of foods and nutrients by weanlings in rural Bangladesh. Am J. Clin. Nutr. 1982;36:878-889.
4. Burri B. J.. Beta-carotene and human healtha review of current research. Nutr. Res. 1997;17:547-580.
5. Christian P., West K. P., Jr, Khatry S. K., Katz J., Shrestha S. R., Pradhan E. K., LeClerq S. C., Pokhrel R. P.. Night blindness of pregnancy in rural Nepal—nutritional and health risks. Intl. J. Epidem. 1998;27:231-237.
6. Darnton-Hill I., Hassan N., Karim R., Duthie M. R.. Tables of nutrient composition of Bangladeshi foodsEnglish version with particular emphasis on vitamin A content. Helen Keller International, Dhaka, Bangladesh 1988;.
7. de Francisco A., Chakraborty J., Chowdhury H. R., Yunus M., Baqui A. H., Siddique A. K., Sack R. B.. Acute toxicity of vitamin A given with vaccines in infancy. Lancet 1993;342:526-527.[Medline]
8. de Francisco, A., Yasui, Y. & Chakraborty, J. (1994) Vitamin A supplementation given to mothers after delivery reduces infant mortality and increases symptoms of morbidity. Paper presented at the XVI International Vitamin A Consultative Group meeting October 24–28, 1994, Chiang Rai, Thailand..
9. de Pee S., West C. E.. Dietary carotenoids and their role in combating vitamin A deficiencya review of the literature. Eur. J. Clin. Nutr. 1996;50 Suppl 3:S38-S53.
10. de Pee S., West C. E., Muhilal , Karyadi D., Hautvast J. G.. Lack of improvement in vitamin A status with increased consumption of dark-green leafy vegetables. Lancet 1995;346:75-81.[Medline]
11. Fauveau V. F.. MatlabWomen, children and health 1994 The International Centre for Diarrhoeal Disease Research, Bangladesh Dhaka, Bangladesh.. .
12. Hossain M. M., Glass R. I., Black R. E.. The prevalence of Ascaris, hookworm, and Trichuris in patients attending a rural diarrhea treatment center in Bangladesh. SE. Asian. J. Trop. Med. Pub. Health 1981;12:539-543.[Medline]
13.
Huffman S. L., Chowdhury A., Chakraborty J., Simpson N. K.. Breast-feeding patterns in rural Bangladesh. Am. J. Clin. Nutr. 1980;33:144-154.
14. Humphrey J. H., West K. P., Jr, Sommer A.. Vitamin A deficiency and attributable mortality among under-5-year-olds. Bull. WHO 1992;70:225-232.[Medline]
15. Jalal, F. (1991) Effects of deworming, dietary fat intake, and carotenoid rich diets on vitamin A status of preschool children infected with Ascaris lumbricoides in West Sumatra province, Indonesia. Doctoral thesis, Cornell University, Ithaca, NY..
16. Katz J., Khatry S. K., West K. P., Humphrey J. H., LeClerq S. C., Kimbrough E., Pohkrel P. R., Sommer A.. Night blindness is prevalent during pregnancy and lactation in rural Nepal. J. Nutr. 1995;125:2122-2127.
17. Kusin J. A., Reddy V., Sivakumar B.. Vitamin E supplements and the absorption of a massive dose of vitamin A. Am. J. Clin. Nutr. 1974;27:774-776.[Abstract]
18. Lucas A., Gibbs J.A.H., Lyster R.L.J., Baum J. D.. Creamatocritsimple clinical technique for estimating fat concentration and energy value of human milk. Br. Med. J. 1978;1:1018-1020.
19. Mahalanabis D., Rahman M. M., Wahed M. A., Islam M. A., Habte D.. Vitamin A megadoses during early infancy on serum retinol concentration and acute side effects and residual effects on 6 month follow-up. Nutr. Res. 1997;17:649-659.
20. . National Research Council (U.S.) Subcommittee on the Tenth Edition of the RDAs. Recommended Dietary Allowances 10th ed. 1989 National Academy Press Washington, D.C.. .
21. Newman V.. Vitamin A and breastfeedingA comparison of data from developed and developing countries 1993 Wellstart International San Diego, CA.. .
22. Olson J. A.. Serum levels of vitamin A and carotenoids as reflectors of nutritional status. J. Natl. Cancer Inst. 1984;73:1439-1444.
23. Pereira S. M., Begum A.. Retention of a single oral massive dose of vitamin A. Clin. Sci. Mol. Med. 1973;45:233-237.
24. Pilch S. M.. Analysis of vitamin A data from the health and nutrition examination surveys. J. Nutr. 1987;117:636-640.
25. Rahman M. M., Mahalanabis D., Wahed M. A., Islam M. A., Habte D.. Administration of 25,000 IU vitamin A doses at routine immunisation in young infants. Eur. J. Clin. Nutr. 1995;49:439-445.[Medline]
26. Roy S. K., Islam A., Molla A., Akramuzzaman S. M., Jahan F., Fuchs G.. Impact of a single megadose of vitamin A at delivery on breastmilk of mothers and morbidity of their infants. Eur. J. Clin. Nutr. 1997;51:302-307.[Medline]
27. Smith P. G. Morrow R. H. eds. Methods for field trials of interventions against tropical diseases: a `toolbox.' 1991 Oxford University Press New York, NY.. .
28. Stoltzfus R. J., Hakimi M., Miller K. W., Rasmussen K. M., Dawiesah S., Habicht J. P., Dibley M. J.. High dose vitamin A supplementation of breast-feeding Indonesian motherseffects on the vitamin A status of mother and infant. J. Nutr. 1993;123:666-675.
29.
Tanumihardjo S. A., Cheng J., Permaesih D., Muherdiyantiningsih , Rustan E., Muhilal , Karyadi D., Olson J. A.. Refinement of the modified-relative-dose-response test as a method for assessing vitamin A status in a field settingexperience with Indonesian children. Am. J. Clin. Nutr. 1996;64:966-971.
30. Thanangkul, O., Promkutkaew, C., Waniyapong, T. & Damrongsak, D. (1974) Comparison of the effects of a single high dose of vitamin A given to mother and infant upon plasma levels of vitamin A in the infant. Presented at a joint WHO/USAID meeting: The Control of Vitamin A Deficiency: Priorities for Research and Action Programmes. NUT/WP/74.I14. November 25–29, 1974. Jakarta, Indonesia. .
31.
Underwood B. A.. Maternal vitamin A status and its importance in infancy and early childhood. Am. J. Clin. Nutr. 1994;59 (suppl):517S-522S.
32. . UNICEF. The state of the world's children 1998 Oxford University Press New York, NY.. .
33. van Dillen J., de Francisco A., Overweg-Plandsoen W. C.. Long-term effect of vitamin A with vaccines. Lancet 1996;347:1705.
34. Wahed M. A., Alvarez J. O., Rahman M. M., Hussain M., Jahan F., Habte D.. Subclinical vitamin A deficiency in young infants from Bangladesh. Nutr. Res. 1997;17:591-598.
35. West, K. P., Jr., Khatry, S. K., Katz, J., LeClerq, S. C., Pradhan, E. K., Shrestha, S. R., Connor, P. B., Dali, S., Adhikari, R., Pokhrel, R. P. & Sommer, A. (1997) Impact of weekly supplementation of women with vitamin A or beta-carotene on fetal, infant and maternal mortality in Nepal. Paper presented at the XVIII International Vitamin A Consultative Group meeting, September 22–26, 1997, Cairo, Egypt..
36. WHO (1996) Indicators for assessing vitamin A deficiency and their application in monitoring and evaluating intervention programmes. WHO/NUT/96.10, World Health Organization, Geneva..
37. . WHO/UNICEF/IVACG Task Force. Vitamin A SupplementsA Guide to Their Use in the Prevention of Vitamin A Deficiency and Xerophthalmia 2nd ed. 1997 World Health Organization Geneva, Switzerland.. .
38.
Zeitlin M. F., Megawangi R., Kramer E. M., Armstrong H. C.. Mothers' and children's intakes of vitamin A in rural Bangladesh. Am. J. Clin. Nutr. 1992;56:136-147.
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