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Plasencia
Plasencia
By
Jessica Plasencia
December 2019
Abstract
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Introduction
preschool aged children and pregnant women. The focus of this review is vitamin A deficiency
in pregnant women. Adequate vitamin A status is critical during times of rapid growth and
development. During times of rapidly differentiating cells, such as during fetal development, the
need for adequate vitamin A stores is greater than usual. While the prevalence of vitamin A
deficiency has decreased over time, it remains a public health concern in many countries
worldwide, especially in developing African countries. Over half of the countries in Africa are
categorized as severe subclinical or as clinical public health concern with regards to vitamin A
status (World Health Organization [WHO], 2010). Nearly 19 million pregnant women suffer
from vitamin A deficiency worldwide (WHO, 2009). More so, this deficiency disproportionately
impacts pregnant women in their third trimester of pregnancy. The inability to acquire adequate
vitamin A stores prior to pregnancy only leads to further depletion and an increased difficulty
replenishing stores before the next pregnancy, leading to a vicious cycle of vitamin depletion.
The purpose of this literature review is to examine and compare the effectiveness of
women in Africa. Vitamin A status was assessed using serum retinol levels in all but one study,
the latter used dark-threshold adaptation to assess vitamin A status. In the present literature
review, the WHO definition of vitamin A deficiency, i.e. serum retinol level ≤0.70/L μmol, is
used to reflect severity. Additionally, night blindness is used to reflect severity and as a health-
related outcome associated with vitamin A deficiency. PubMed and Cal Poly One Search were
used to search journal articles using key phrases including “maternal vitamin A deficiency”,
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Observational and experimental studies were utilized in this review. These articles included
Vitamin A Importance
Vitamin A has many functions including regulation of gene expression, vision, cellular
differentiation, and immunity. Carotenoid and retinoid forms of the vitamin have independent
functions playing key roles in proper eye development. Vitamin A also forms rhodopsin, a
pigment protein located in the light-receptors, or rods, of the retina. Vitamin A has several
immune system functions including the ability to maintain T-lymphocyte function and antibody
response. Without proper vitamin A stores, the ability to fight off infection is compromised
(Gropper et al., 2018). Due to the multitude of its functions, vitamin A deficiency may increase
the risk of maternal morbidity while also being a major cause of preventable night blindness in
typically associated with low levels of vitamin A intake or stores (clevandclinic.org, 2019).
When a flash of light hits the retina, vitamin A in cis-retinal form is converted to trans-retinal
form, cleaving a rhodopsin molecule in the process. When this process is reversed and the eye
encounters darkness, the rhodopsin must be reformed using cis-retinal. If vitamin A stores are
depleted, the rhodopsin is unable to reform and the ability to adjust to low light is compromised
(Gropper et al., 2018). Pregnant mothers, particularly those entering pregnancy with low vitamin
A stores, are disproportionately affected by night blindness during their last trimester of
pregnancy due to further depletion of stores by the increased needs of the growing fetus.
Vitamin A in retinoic acid form plays a role in immune function. Retinoic acid stimulates
phagocytic and natural killer cell activity. Additionally, depletion of vitamin A stores affects T-
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lymphocyte cell function. T-lymphocytes are non-antibody producing cells that can become
cytotoxic cells or memory cells. The key advantage of memory cells is their near instant humoral
If vitamin A levels are low and T-lymphocytes are not produced at adequate levels, then the
capacity to combat viral, parasitic, and bacterial infections is compromised (Marieb et al., 2015).
Hanson, et al (2018) studied the serum retinol and carotenoid levels of mother-infant
pairs in the U.S. and Nigeria to study the prevalence of maternal vitamin A deficiency,
associated health outcomes, and effects on infant vitamin A levels. The comparison of findings
between a developed and developing country is not only helpful in comparing prevalence, but
also in analyzing possible distinctions responsible for group disparities in vitamin A status. This
comparative study had a total of 278 participants. Excluded were mother-infant pairs with
metabolic errors. In Nigeria, 99 mother-infant pairs enrolled to the antenatal clinic at the
University of Abuji Teaching Hospital in Nigeria were recruited to participate in the study. Of
the mother-infant pairs recruited, only 84 mothers and 74 infants had usable blood samples. In
the U.S., 179 mother-infant pairs were strategically recruited from Nebraska Medicine Hospital’s
labor and delivery units to represent the U.S. demographic, however, only 176 mothers and 167
Cord and maternal blood samples were collected at the time of delivery to determine
vitamin A status, serum retinol levels, and serum carotenoid levels of mother-infant pairs. Along
with serum samples, infant birth anthropometrics and sex, as well as, maternal age, BMI, and
smoking status were collected. In Nigeria, the hospital followed up with a phone interview 28
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days after the hospital discharge date to evaluate mother-infant pair well-being and collect
information regarding any postnatal hospitalizations. In the U.S., mother-infant pair information
regarding health status was collected from hospital records (Hanson et al., 2018).
Table 1. Serum retinol status of mother and infants in the U.S. and Nigeria (Hanson, et al 2018)
The Nigerian mothers demonstrated nearly four times higher rates of vitamin A
deficiency than the U.S. mothers, 35.5% versus 9.3% (Table 1). Nigeria demonstrated almost
double the amount of severely deficient infants, 14.8%, then the U.S., 7.6% (Table 1). Although
both the Nigerian mothers and infants demonstrated elevated rates of vitamin A deficiency, the
two were not found to be correlated (p=0.66). Notably, while Nigerian mothers had higher pro-
vitamin A levels than U.S. mothers, they still demonstrated a higher prevalence of vitamin A
deficiency. This could be attributed to the plant-based diet of the Nigerian population that is
higher in the lower bioavailable pro-vitamin A. One limitation of this study was the small sample
size in relation to the prevalence estimate of the country represented (Hanson at al., 2018).
vitamin A deficiency is a public health concern. The International Vitamin A Consultative Group
(IVACG) defines severe public health concern as 5% of the population having a vitamin A
deficiency. In Africa, this percentage is nearly doubled at 13.5% (WHO prevalence report,
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2009). While it is clear that action must be taken, the appropriate method for supplementation of
approach of a weekly low-dose supplement of vitamin A in Nepal. The primary goal of this trial
The study population consisted of all women aged 15-45 who lived in the seven
prominent districts in the Brong Ahafo Region of Ghana. Women were randomly assigned,
according to their cluster of residence, a vitamin A capsule or a placebo capsule with identical
appearance and taste. The vitamin A capsule contained 25,000 IU retinol equivalents in soybean
oil to enhance absorption. The placebo capsule only contained soybean oil. Women were given 4
capsules in a vial at a time and were instructed to take the supplement weekly. Every four-weeks,
the women were visited at home to receive their next vial, however no direct observation of
capsule consumption took place. Distribution of capsules begun in December 2000. All
distribution stopped in September 2008 and all data collection stopped in October 2008. In order
program was formed. This educational program was held every Sunday and encouraged women
to consume the capsule that day, to create a sense of community and support while reducing
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forgetfulness. The IEC group addressed any adherence problems through regularly held focus
groups. During home visits to distribute capsules, data was collected regarding any pregnancies,
consumption. Between March 2003 and May 2003, a sub-study was held. 200 randomly selected
participants were surveyed to assess night blindness within the sample population. Between
September 2008 and October 2008, a second sub-study was held. This time, 440 pregnant
women and 440 women who had not been pregnant in the last year were randomly selected to
give 5 mL of venous blood to assess serum retinol concentrations (Kirkwood et al., 2010).
This trial continued for 8 years, with an average participation duration of 4.5 years, and a
total of 9,440 participants. Adherence to consumption was high. 88.2% of women self-reported
consumption of all four capsules and 84.3% consumed all four based on observed capsules left in
their vial. However, results of this trial suggest that weekly vitamin A supplementation in this
population had no beneficial effect on maternal morbidity, mortality, or vitamin A status. There
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hospital admissions (2342 admissions for placebo vs 2332 admissions for supplement). There
was also no significant difference found between mortality rates of the two groups. Vitamin A
supplemented groups had 115 pregnancy-related deaths and the placebo group had 110 deaths,
p=0.80 (Table 3). In the 2008 sub-study, there was no indication of vitamin A supplementation
having any effect on serum retinol levels. Interestingly, the vitamin A supplementation group of
women had higher level of deficiency, 25%, than the placebo group, 15.4% (Table 3). Notably,
the placebo group was given oil capsules to consume weekly, essentially, increasing vitamin A
absorptivity. The study conducted in Nepal concluded that maternal mortality could be reduced
by 44% in the sample population through a weekly, low-dose vitamin A supplement (West et al.,
1999). Reasons inhibiting paralleled results between the populations studied, could be
participants affected by night blindness, while this population demonstrated a rare number of
women affected. The study concluded that there is no benefit to an inclusion of a low-dose
aid in consuming adequate amounts of said nutrient. However, due to the wide variety of
nutrients within whole foods, a supplement cannot completely replace the nutrient diversity of a
healthy diet (National Institute of Health [NIH], 2011). In several countries in Africa, societal
norms require women to feed their family members before themselves, limiting nutrient status
and increasing risk of micronutrient deficiency. Despite animal sources having the most
bioavailable form of vitamin A, due to low-income status, women often rely on plant sources of
vitamin A (Lietz et al., 2001). The findings of the Kirkwood et al., 2010 study and Africa’s
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deficiency status suggests that, perhaps, the appropriate approach to improving micronutrient
Food-Based Approach
Ethiopia to analyze vitamin A status. This study attempted to find behavioral correlation between
women and adequate vitamin A status. 104 pregnant women were randomly selected for this
study. To perform the dark adaptation threshold, each woman was first adapted in a dark tent for
ten minutes. Each woman was then asked to read black letters on a white background in a dark
room. The room’s light level was tested by researchers prior to the study to assure the subjects
were being asked a reasonable task. The women’s pupillary response was measured using a
Scotopic Sensitivity Tester-1 (SST-1). This tester consists of an illumination device, ranging
from 0 to 30 decibel intensities. The women were tested based on their pupillary response to
illuminations at this range of light intensities. Women were also asked to provide a 24-hour
dietary recall. Dietary diversity scores were given on a scale from 1 to 10 based on the number of
The study population was 27.5±6.1 years old at 28±7 weeks of gestation. Of these
women, 80.7% had been pregnant previously. 91.3% of the women sampled had heard of night
blindness before, indicating high prevalence of the issue within the community. Of the women
who had given birth in the past three years, 12.9% had experienced night blindness themselves;
older women, those with no formal education, and those in their third trimester of pregnancy had
a higher proportion affected. The dietary diversity scores revealed that 50% of participants
received a dietary diversity score of less than 3, and only 18.3% received a dietary diversity
score over 6. Women with formal education had higher dietary diversity scores and showed
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significantly higher consumption of animal-source vitamin A foods (p=0.003) and slightly higher
consumption of plant-source vitamin A foods (p=0.082). For each unit increase in dietary
diversity score, there was a decrease in dark adaptation threshold (p=0.001). Therefore, dietary
approach to vitamin A deficiency. Although this study did not indicate any design limitations,
the statistical approach of this study was poorly described. Sufficient narrative explained the
study process; however the results were presented rather vaguely (Hiwot et al., 2014).
The absorption of carotenoids varies but can be up to 60% in pure oil form. Leitz, et al
status in breastfeeding mothers and pregnant women in Tanzania. Red palm oil was the chosen
food-based source of vitamin A due to its dual role in providing provitamin A and oil to enhance
absorption. The population studied consisted of 90 women in their third trimester of pregnancy
from 20 different villages in Tanzania. This study excluded women with severe anemia and
dietary intake between the groups. This was determined based on several variables such as
access to water and electricity, and income. All but one of the women were small-scale farmers.
In order to minimize crossover of the different supplement types, the women were allocated into
three groups based on supplement likeness and then separated by distance. The different
supplement groups had a minimum of 3km of distance among them. The study compared a
control group, a group administered sunflower oil (low in vitamin A), and a group administered
red palm oil (rich in provitamin A) to compare outcomes of serum and breastmilk retinol, alpha-
carotene, and beta-carotene levels. Each group was encouraged to consume green leafy
vegetables with their allotted oil; the control group paired their greens with rice. Oil was
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distributed monthly throughout the last trimester of pregnancy and three months postnatal; a total
of six months. Each woman was given enough oil to feed their entire family, giving all members
the potential to benefit from the study. Each woman was taught how to incorporate the oil into
traditional meals and warned of the dangers of heating oil past the smoke point. Distribution of
oil was done in public spaces in the village. During this time, women completed questionnaires,
gave blood and breast milk samples, and were assessed anthropometrically. Blood samples were
used to analyze plasma alpha-carotene, beta-carotene, and serum retinol levels. Breastmilk
samples were used to analyze alpha-carotene, beta-carotene, retinol levels, and milk fat
percentage which affects newborn absorption of vitamin A. At the start of the study, there were
no significant differences in plasma nutrient composition between groups (Lietz et al., 2001).
Table 4. Plasma retinol, alpha-carotene, and beta-carotene levels at baseline (during third
trimester), one month, and three months postpartum (Lietz, et al 2001).
At one month postpartum, the red palm oil group’s plasma alpha- and beta-carotene
concentrations were 42 times and 3 times higher than the control group (Table 4). At three
months postpartum, this difference remained significant at 51 times greater for alpha-carotene
and 4 times higher for beta-carotene (Table 4). However, no significant difference was found in
plasma retinol levels at one or three months postpartum, p=0.94. Unlike the control group, both
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the red palm oil and sunflower oil groups demonstrated a maintenance of alpha- and beta-
carotene levels between one and three months postpartum. Breastmilk alpha- and beta-carotene
concentrations were significantly higher per kilogram milk fat in the red palm oil group than the
This study indicates that red palm oil increases alpha- and beta-carotene concentrations in
plasma and breastmilk (Table 4, Table 5). No group showed a significant difference in change in
retinol levels, however both the red palm oil group and the sunflower oil group showed much
higher postpartum retention rates than the control group. This could be due to oil increasing
absorption and retention of vitamin A. The overall increase in serum retinol of all groups can be
attributed to the increased consumption of dark green leafy greens and fat; typically this
Table 5. Concentration of breastmilk retinol, alpha-, and beta-carotene levels at one month
and three months postpartum (Lietz, et al 2001).
Red palm oil is widely produced in West Africa, however proper cooking technique is
not as common. Red palm oil is commonly used for deep-fat frying and vegetables consumed are
commonly blanched, decreasing nutrient availability. For this reason, the population was
instructed how to prepare dishes while preserving vitamin A bioavailability. Although further
research is needed, red palm oil consumption is considered of added benefit for increased plasma
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and breastmilk alpha- and beta-carotene levels and maintenance in the sample population (Lietz
et al., 2001).
In the 2010 Ghana study by Kirkwood et al., the weekly vitamin A supplement
demonstrated no increase in serum retinol levels when compared to the control group. Although
in the study by Lietz et al., 2001 there was no significant difference in serum retinol
concentration increases between the three groups, there were substantial increases across all
groups. The lowest increase observed being the control group, from 0.94 μmol to 1.14 μmol
(Table 4). The commonality between groups was increased consumption of vitamin A rich whole
foods. The red palm oil and sunflower oil groups were instructed to consume 4 tbsp of oil and
avoid cooking past the smoke point. When paired with proper cooking techniques, the increased
consumption of plant-source vitamin A foods proved to increase serum retinol, alpha-, and beta-
Busse, et al., 2017 conducted a cross-sectional study in five rural districts of Ethiopia.
The populations’ knowledge of vitamin A rich source, vitamin A deficiency, and associated
deficiency caused by common population practices. These rural areas have demonstrated
difficulty meeting nutritional recommendations in the past due to low health care access.
The sample population consisted of 150 mothers with at least one child between 6-59
months old. The population was surveyed to assess general knowledge of vitamin A, nutrition
consumption behaviors, family production of potato, white fleshed sweet potato (WFSP), and
orange fleshed sweet potato (OFSP), and health status indicators. The research team considered
that food choice extends beyond simply selecting a food item, and considered social and cultural
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The average maternal age was 36.4 years old. The average woman was married at 16.9
years old and had her first child at 17.8 years old. In a woman with poor vitamin A status, each
child means a further depletion of micronutrient stores. On average, the women in this
Table 6. Comparison of maternal consumption of potato crops in the past seven days, separated by
district (Busse et al., 2017).
Production and consumption of potatoes varied across the included distircts. The Boricha
and Duguna districts produced the most potato and WFSP. The Damot Gale produced the most
OFSP. Due to societal norms in many African countries, women often feed their family members
before themselves, indicated by the difference between household production and average
maternal consumption of potatoes. On average, only 15% of the women sampled reported
consuming potato crops in the past seven days. Also, due to traditional low-fat consumption,
none of the districts paired vitamin A sources with a fat source to enhance absorption (Table 6).
The lack of vitamin A and fat pairing could be a strong determinant for relatively high rates of
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Notably, the district of Damot Woyide was the only district with OFSP consumption
(Table 6). One medium OFSP can provide well over 100% of the daily recommendations for
vitamin A (Ware, 2017). Notably, this district had lower history of eye problems and night
blindness when compared to many other districts, indicating improved vitamin A status (Table
7). Thus, the increased consumption of OFSP is beneficial to eye health (Busse et al., 2017).
Table 7. Comparison of maternal health practices and outcomes, separated by district (Busse
et al., 2017)
This study concluded that the best way to improve vitamin A deficiency related health
implications is through the consumption of vitamin A rich crops, specifically OFSP. Not only
will this improve vitamin A status, but it may additionally help improve other micronutrient
deficiencies due to the high nutrient variety in whole foods. This practice is a more economically
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capsule form. While this survey accurately reflected vitamin A practices and knowledge of the
five rural communities sampled at this time, it does not reflect all of Ethiopia or this population
completely due to large seasonal variation in food consumption. This survey was held at the end
of the belg season, or the secondary harvest season, which tends to have lower food production
and stores than the primary harvest season (Busse et al., 2017).
The present literature review assessed supplement- versus food-based approaches and their
effects on vitamin A status. One experimental study was reviewed to evaluate vitamin A
supplementation effectiveness. One observational and two experimental studies were reviewed to
risk for this deficiency due to the increased vitamin A needed to support fetal growth and
development. Women in Africa have a much higher prevalence of vitamin A deficiency when
compared to women in the United States, 13.5% vs 2% (Table 2). With a deficiency prevalence
over 5% indicating public health concern, the current vitamin A status in African pregnant
has not proven beneficial in African countries (Kirkwood et al., 2010). The weekly supplement
administered in the Ghana study contained 25,000 IU retinol equivalents paired with soybean oil,
but the capsule alone did not significantly affect vitamin A status (Kirkwood et al., 2010).
Animal sources of vitamin A have an increased absorbance rate in the body, however, due to
lower socioeconomic status and food availability, plant-based diets are more common in Africa.
Notably, while having a lower bioavailability, the plant sources of vitamin A proved beneficial to
vitamin A status and related health outcomes when cooked correctly and supplemented with a fat
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source (Hiwot et al., 2014; Lietz et al, 2001). The red palm oil was particularly beneficial in
increasing serum and breastmilk beta-carotene levels (Lietz et al, 2001). In the observational
study conducted by Hiwot et al., 2014 dietary diversity was correlated to decreased dark
threshold adaptation, p=0.001. Although the red palm oil study conducted by Lietz et al., 2001
did not assess eye health, carotenoids play key roles in eye development and maintenance.
Further research is needed to correlate increased red palm oil intake and eye health status.
A status in pregnant women in Africa, while constituting a safe source of vitamin A for the entire
community to consume. Additionally, this approach is more sustainable and economically sound,
and may increase jobs, income, crop production, and sales, while potentially, addressing issues
of social inequality and food insecurity. Future research is needed to identify the most beneficial
types of foods that will be self-sustainable year-round in African communities, and intake
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Table 8. Summary of Research Studies Evaluated
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Busse, H., Kurabachew, H., Ptak, M., & Fofanah, M. (2017). A food-based approach to reduce
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