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Johns Hopkins School of Public Health, Baltimore, MD 21205 and * The Society for Prevention of Blindness, Kathmandu, Nepal
2To whom correspondence should be addressed. E-mail: pchristi{at}jhsph.edu.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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KEY WORDS: • maternal night blindness • infants • mortality • vitamin A • ß-carotene
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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. Prematurity, intrauterine growth
retardation and infectious morbidity due to acute lower respiratory
infection rates, neonatal tetanus, sepsis and diarrhea are the major
causes of infant mortality (2)
. Night blindness during
pregnancy is common at 18% prevalence (3)
and is
associated with increased risk of inadequate vitamin A intake,
reproductive morbidity, anemia and wasting malnutrition among women in
Nepal (4)
. A community-based, randomized trial of
vitamin A and ß-carotene supplementation to women of reproductive age
in Nepal yielded the following three key findings: 1)
supplementation resulted in a 40–49% reduction in
pregnancy-related mortality (5)
; 2) night
blindness during pregnancy was associated with a significantly higher
risk of subsequent mortality in women, a risk that was largely
ameliorated with supplementation (6)
; and 3)
there was no effect of either supplement on fetal loss and mortality up
to 6 mo of life (7)
. In this paper, we hypothesized that
mortality in the first 6 mo of life may be elevated among infants of
women who suffered from night blindness during pregnancy because they
are at an increased nutritional and health risk. We examined this
relationship in the cohort of women and infants who were followed in
the vitamin A, ß-carotene supplementation trial. |
SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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6
7)
. Briefly, 426 communities of the southeastern Terai
district of Sarlahi were randomized for women of reproductive age to
receive, once a week, vitamin A as retinyl palmitate [7000
µg retinol equivalents
(RE)3
], all-trans ß-carotene (42 mg or 
7000 µg
RE) or placebo. The supplements were identical in shape, size and color
and were made by Roche, Basel, Switzerland. They were opaque gelatinous
capsules containing peanut oil and 5 mg dl-
-tocopherol as
an antioxidant. Locally hired women administered the supplements each
week to women of reproductive age in their area, and also identified
pregnancies. Women were randomized to one of the three allocation
groups, 6 mo before the commencement of pregnancy enrollment, thus
allowing at least 6 mo of supplementation before pregnancy declaration.
Data for this analysis cover pregnancies reported and outcomes that
occurred over a period of 3 y, beginning from the last week of July
1994 until the first week of April,1997. These dates allowed a 6 mo
follow-up to determine the survival status of infants after birth,
until the study’s termination in October 1997.
In two thirds of the study area, a weekly night blindness surveillance
was set up to identify cases of night blind pregnant women. The locally
hired women were also trained to elicit night blindness histories using
the local term for this condition in the surveillance area. The
standard question used was "Are you currently night blind (local
term)?" Night blindness is a well-recognized condition in the
community (8)
and is strongly associated with vitamin A
deficiency among pregnant women in Nepal (4)
. Once a study
woman reported being pregnant, she was asked every week until the end
of her pregnancy whether she had developed night blindness. Women were
considered cases if they had reported being night blind at least once
during pregnancy.
Pregnant women were interviewed twice during pregnancy and at 3 and
6 mo postpartum regarding their dietary intake, history of morbidity
symptoms, alcohol and tobacco use, and work, using a 7-d recall. Data
on previous pregnancy history and household socioeconomic
characteristics were also collected at the time. Vital status of
infants was ascertained at the postpartum visits.
Statistical analysis.
Because mortality of infants among women without night blindness was
similar across groups receiving placebo, vitamin A or ß-carotene,
these three groups were combined and used as the reference category.
However, night blind/placebo, night blind/vitamin A and night
blind/ß-carotene groups were categorized separately. Kaplan Meier
survival analysis was used to examine the difference in mortality among
infants up to 6 mo among the four groups (9)
. Logistic
regression analysis was done using 6-mo mortality in infants as the
outcome and maternal night blindness and supplementation status coded
as indicator variables. Confounding effects of variables such as
parity, gestational age at birth, mid-upper arm circumference and
symptoms of morbidity during pregnancy were adjusted in the logistic
regression analysis. Only symptoms of morbidity that were significantly
associated with mortality were retained in the final model. Both
unadjusted and adjusted odds ratios (OR) with the 95% confidence
interval (CI) were calculated. A P-value < 0.05
was considered significant. All analyses were performed using SAS
version 6 statistical software (SAS Institute, Cary, NC).
Ethical approval for the study was obtained from the Nepal Health Research Council, Kathmandu, Nepal and the Joint Committee on Clinical Investigation and the Committee on Human Research at the Johns Hopkins School of Medicine and Public Health, Baltimore, MD. Verbal informed consent was provided by women.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). A small number (3–7%) of infants were lost to follow-up due to
out-migration from the study area, and their vital status was
unknown. Loss to follow-up was similar between treatment groups and
by night blindness status, although losses were slightly higher among
infants of non-night blind women relative to those of the night
blind women. Overall, 605 infants died by 6 mo postpartum, at a rate of
90/1000 live births among night blind women and 63/1000 live births
among non-night blind women. As mentioned previously, although 6-mo
mortality among infants did not vary significantly by supplement group
among women never reporting night blindness, mortality risk was higher
and varied among infants of night blind women across the three
different supplement groups.
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). Mortality was the highest among infants of women who were in the
placebo group and had night blindness during pregnancy (99/1000 live
births), followed by 91/1000 live births among ß-carotene and 74/1000
live births among vitamin A recipients with night blindness. The
mortality of infants of non-night blind women was similar and was
63/1000 live births for the three groups (placebo, vitamin A,
ß-carotene) combined.
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). Infants of night blind mothers were found to have a 63% excess risk
of mortality in the first 6 mo of life (OR = 1.63 95%; CI:
1.09–2.38) over those of non-night blind mothers, after adjustment
for confounding factors. Infants of night blind mothers receiving
ß-carotene had a 50% excess risk of mortality compared with those of
women without night blindness, although the CI includes unity (OR
= 1.50; 95% CI: 0.97–2.33). The risk of mortality among infants
of night blind women receiving vitamin A was only 14% (OR
= 1.14; 95% CI: 0.67–1.93) higher than observed among infants of
non-night blind mothers.
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|
DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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.
The increased mortality in the first 6 mo of life in infants may be
related to the numerous associated health and nutritional risks faced
by night blind mothers that may stress the pregnancy and consequently
the infant. These factors include a diet lacking adequate vitamin A,
hyporetinolemia, anemia, wasting malnutrition and morbidity during
pregnancy reflected by frequent reporting of diarrhea, nausea,
vomiting, poor appetite and symptoms of urinary/reproductive tract
infections (4)
.
Maternal vitamin A or ß-carotene supplementation at normal dietary
levels before and during pregnancy reduced the risk of night blindness
during pregnancy by 70% among women who consumed 95–100% of their
weekly vitamin A supplements throughout pregnancy (10)
.
ß-Carotene, on the other hand, only reduced risk of maternal night
blindness by 17% (95% CI: -9 to 37%). Thus, high compliance with
supplementation and the form in which the vitamin A was given
influenced its protective effect against night blindness.
Previously we reported that vitamin A and ß-carotene supplementation
to women failed to reduce overall mortality of infants up to 6 mo of
age (7)
. The present analysis, however, indicates that
compared with the mortality up to 6 mo of age among infants of
non-night blind women, the risk of mortality was 1)
markedly elevated (by 63%) in infants of placebo-recipient mothers
who developed night blindness during pregnancy; 2) slightly
lower, yet still remarkably high (50%) among infants of mothers
receiving ß-carotene who developed night blindness during pregnancy;
and 3) only slightly higher (14%) among infants of
vitamin A–receiving night blind mothers. This last group may represent
a high risk mother-infant dyad among whom routine vitamin A receipt
remained inadequate to resolve maternal night blindness but was
sufficient to meet critical fetal/infant needs to improve survival.
ß-Carotene did not appear to do as well, either in preventing night
blindness in women during pregnancy or in reducing the elevated
mortality in the first 6 mo of life among infants of night blind women.
These findings reinforce the potential clinical significance of a history of maternal night blindness during pregnancy. In this Nepalese population, the condition identified an acute, high risk situation for both the mother and her infant. Maternal night blindness could be a valuable prognostic tool for identifying high risk pregnant women in need of antenatal and postnatal vitamin A supplementation, nutritional care and health services.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: CI, confidence interval; OR, odds ratio; RE, retinol equivalent.
Manuscript received October 31, 2000. Revision accepted January 17, 2001.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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1. United Nations Children’s Fund The State of the World’s Children 1998 UNICEF New York, NY.
2. Child Health Research Project Special Report Reducing Perinatal and Neonatal Mortality. Report of a Meeting 1999;3, no. 1 Baltimore, MD
3. National Family Health Survey Bureau of Statistics, His Majesty’s Government of Nepal 1996 Kathmandu Nepal.
4.
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. Int. J. Epidemiol. 1998;27:231-237
5.
West K. P., Jr, Katz J., Khatry S. K., LeClerq S. C., Pradhan E. K., Shrestha S. R., Connor P. B., Dali S. M., Christian P., Pokhrel R. P., Sommer A., NNIPS Study Group Low dose vitamin A or ß-carotene supplementation reduces pregnancy-related mortality: a double-masked, cluster randomized prevention trial in Nepal. Br. Med. J. 1999;318:570-575
6.
Christian P., West K. P., Khatry S. K., Kimbrough-Pradhan E., LeClerq S. C, Katz J., Shrestha S. R., Dali S. M., Sommer A. Night blindness during pregnancy and subsequent mortality among women in Nepal: effects of vitamin A and ß-carotene supplementation. Am. J. Epidemiol. 2000;152:542-547
7.
Katz J., West K. P., Jr, Khatry S. K., Pradhan E. K., LeClerq S. C., Christian P., Wu L.S.F., Adhikari R. K., Shrestha S. R., Sommer A. Low-dose vitamin A or beta-carotene supplementation does not reduce early infant mortality: a double-masked, randomized, controlled community trial in Nepal. Am. J. Clin. Nutr. 2000;71:1570-1576
8. Christian P., Bentley M. E., Pradhan R., West K. P., Jr An ethnographic study of night blindness "ratauni" among women in the Terai of Nepal. Soc. Sci. Med. 1998;7:879-889
9. Kahn H. A., Sempos C. T. Statistical Methods in Epidemiology 1989 Oxford University Press New York, NY.
10.
Christian P., West K. P., Jr, Khatry S. K., Katz J., LeClerq S. C., Pradhan E. K., Shrestha S. R. Vitamin A or ß-carotene reduces but does not eliminate maternal night blindness in Nepal. J. Nutr. 1998;128:1458-1463
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