Public Health Crisis of Anemia in India: Retrospective Study of Hemoglobin Levels and Impact of Medication Intervention in a School Setting

doi:10.21203/rs.3.rs-2759496/v1

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Public Health Crisis of Anemia in India: Retrospective Study of Hemoglobin Levels and Impact of Medication Intervention in a School Setting

https://doi.org/10.21203/rs.3.rs-2759496/v1

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Background

Anemia has been a pervasive and constant public health crisis in India. Anemia’s prevalence in rural areas is 79% in children and 49.5% in women.A large survey of adolescent girls reported an anemia prevalence of 89%, of which 56% have iron deficiency anemia. The objectives of this study are to understand the prevalence of iron deficiency anemia in children and women from rural villages in India and the impact of a medication and health education intervention on hemoglobin levels, utilizing an existing local community structure of a boarding school.

Methods

Retrospective study of de-identified hemoglobin data originally collected during a public health clinical care investigation was performed to understand the prevalence of anemia in women and children in rural villages. Participants gave blood samples to measure hemoglobin levels. Analysis of health education and medication intervention consisting Albendazole 200 mg and Autrin Capsule tablets containing cyanocobalamin vitamin B12 (0.1% in gelatin), ferrous fumarate (98.6 mg of elemental iron), and folic acid with lemon water given to 275 female students at Kaneria Boarding School was performed to understand the impact of intervention on hemoglobin levels.

Key Results

Utilizing the World Health Organization (WHO) anemia classification, prevalence of moderate and severe anemia ranged 20-60% amongst women and children. Results from an interventional study showed a statistically and clinically significant increase in hemoglobin levels of 2.848 (p<0.05) in 10^th grade and 2.423 (p<0.05) in 12^th grade students.

Conclusions

Understanding the prevalence of anemia in rural regions in India is imperative to focusing therapies targeting iron deficiency anemia. Results of an interventional study utilizing existing community structures such as a school holds promise for future wide-scale iron deficiency anemia interventions.

Iron deficiency anemia

Anemia

Public Health

Prevalence

India

Anemia is a general classification of when the body has a low number of red blood cells, which are needed to carry oxygen to tissues in the body. In iron deficiency anemia (IDA), there is a lack of iron that is an integral component of hemoglobin, the oxygen-carrying molecule in red blood cells. Other forms of anemia can arise due to a lack of vitamin B12, folic acid, and other micronutrients. IDA may lead to negative health outcomes such as fatigue and shortness of breath, which could make it difficult to work, in addition to further exacerbating congestive heart failure.⁴ In addition, IDA may lead to an increased risk of infection.⁵ Although IDA is not fatal in the near term, if the etiology underlying the IDA is not addressed then this could lead to poor outcomes.⁴ Anemia has been linked to significantly impairing overall survival for individuals over 60 years old.⁶ It has been found that low iron has a negative impact on reproductive age women’s cognitive function.⁷ When iron deficiency is corrected in adults, there is an improvement of cognitive function.⁷

IDA is a prevalent public health crisis around the world.⁹ India in particular has had a consistently high prevalence of IDA based on the National Family Health Survey, which began in 1991.¹ According to the review of literature, women have a high prevalence of anemia, with findings being over 49.5%.² In studies of children in India, it is found that anemia was found in 89% of adolescent girls.³ Of those, 56% are affected by IDA. Previous studies have shown a prevalence of 17% mild, 65% moderate and 5% severe anemia in girls.³

IDA is prevalent among people in India due to low consumption of iron among females, with the medium iron consumption being 13.7 mg/day while the recommended daily consumption of iron is 15–18 mg/day.¹⁰ This may be due to a typical diet low in iron and containing non-heme iron, including grains, plants, cereals, lentils and vegetables. Iron may be obtained from iron supplements and iron-fortified foods, but are not as readily absorbed as compared to sources of heme iron such as meat and fish.¹⁰ Although there is a standard guideline for iron-folic acid supplementation in place, the iron-folic acid interventions appear to be ineffective in reducing the burden of IDA in India.¹⁰

In addition to low dietary intake of iron, India accounts for roughly 25% of the global cases of soil-transmitted Helminth infections (Ascaris lumbricoides, hookworm, and Trichuris trichiura), affecting over 220 million children.¹¹ These helminth infections further contribute to the malabsorption of iron and essential nutrients, exacerbating IDA. Of note, recent findings suggest that a single dose of albendazole, a common deworming medication, can effectively treat hookworm infections.⁹ Furthermore, lack of health education covering the ways people can acquire greater iron intake through lifestyle and dietary modifications may have contributed to the prevalence of IDA in at-risk populations.

The state of Gujarat, India has not been focused on in great depth for the prevalence and severity of anemia. Those from rural villages are particularly understudied and there is little research on IDA intervention studies in many of these regions. Researchers at the University of California, Irvine School of Medicine sought to understand the prevalence of IDA in the rural villages of Dhank, Kolki, and Bhimora, Gujarat. The initial study analyzed hemoglobin level data to understand the prevalence of anemia amongst children and women in these villages. Researchers then sought to understand the impact of an IDA intervention by administering vitamin supplements to 10th and 12th grade girls at an all-girls boarding school, Kaneria Boarding School, in Junagadh, India.

This is a retrospective analysis of de-identified data collected during a 2010–2015 public health clinical care investigation of hemoglobin levels and medication interventions in several villages in India. The University of California, Irvine Institutional Review Board determined the current study to be non-human subjects research because the data does not contain any identifying protected health information.

In the villages of Dhank, Kolki, and Bhimora, prevalence of anemia was determined from blood samples taken to measure hemoglobin levels. There were two sample groups: children ages 0–18 (n = 17,111) and women ages 18–45 (n = 9,151). Researchers calculated the mean hemoglobin levels and then classified the prevalence of anemia for each group based on World Health Organization (WHO) criteria.¹²

The intervention study focused on 10th (n = 200) and 12th (n = 75) grade girls at an Kaneria Boarding School in Junagadh. These girls came from a rural farming background, and received education, board, and stay at the boarding school. In a supervised setting, the students were given one dose of deworming tablets (albendazole 200 mg), followed by 1 week rest, and then Autrin Capsule tablets containing cyanocobalamin vitamin B12 (0.1% in gelatin), ferrous fumarate (98.6 mg of elemental iron), and folic acid with lemon juice every day for 100 days. Autrin was given after an initial assay showed 30% low vitamin B12 levels in that area. Along with the supplementation, the students were given a health education presentation on IDA and nutrition. Blood samples were taken to measure hemoglobin levels (g/dl) before and after the 100 days of treatment. Researchers calculated the difference in means for hemoglobin levels using two-tailed paired t-test analysis with a p value threshold for statistical significance ≤ 0.05. Classification for anemia severity was made based on the WHO criteria.

The results show levels of moderate and severe anemia within the states of Kolki, Bhimora, and Dhank for children aged 0–18 and women aged 18–45. Amongst children, the highest level of moderate to severe anemia was in Bhimora. The lowest level of severe anemia and highest level of no anemia were in Kolki. Similar results were seen amongst women. with the highest level of both moderate and severe anemia were in Bhimora. The lowest level of severe anemia and highest level of no anemia were in Kolki (Table 1, Fig. 1, Fig. 2).

Table 1

Prevalence of Anemia determined by WHO criteria in Children 0–18 and Women 18–45 in Kolki, Dhank, and Bhimora
Children 0–18	Non-anemic	Mild anemia	Moderate anemia	Severe anemia
Kolki (n = 8,994)	12%	53%	33%	1%
Bhimora (n = 4,013)	2%	28%	65%	4%
Dhank (n = 4,104)	1%	28%	56%	2%
Women 18–45
Kolki (n = 3,516)	20%	62%	19%	1%
Bhimora (n = 2,985)	1%	34%	64%	1%
Dhank (n = 2,688)	4%	43%	53%	0%

The results show hemoglobin levels for the girls at Kaneria Boarding School before and after receiving the 100 day treatment of albendazole (200mg), cyanocobalamin (vitamin B12) (0.1% in gelatin), ferrous fumarate (98.6 mg of elemental iron), and folic acid. Both the 10th and 12th grade students showed a significant increase in hemoglobin levels post treatment and a change from moderate anemia to no anemia based on WHO Criteria (Table 2).

Table 2

Pre and post medication intervention hemoglobin levels in students at Kaneria Boarding School
School Grade	Mean Pre- intervention Hb level	Mean Post- intervention Hb level	Mean difference in Hb level	P-value	Change in WHO Classification
10 (n = 199)	10.20 (SD = 0.98)	13.05 (SD = 1.32)	-2.85 (Sp: 1.35, 95% CI: -3.08, -2.62)	P-value < 0.001 (t= -24.48)	Moderate to Non-anemia
12 (n = 75)	10.52 (SD = 1.22)	12.95 (SD = 1.31)	-2.42 (Sp: 1.26, 95% CI:-2.83, -2.05)	P-value < 0.001 (t= -11.74)	Moderate to Non-anemia

Iron Deficiency Anemia is a serious public health crisis within the state of Gujarat, India. This was studied in the villages of Kolki, Bhimora, and Dhank where women and children have a high prevalence of moderate and severe anemia based on WHO classification. An intervention utilizing the existing social structure of a boarding school consisted of albendazole deworming tablets and supplementation of cyanocobalamin vitamin B12 (0.1% in gelatin), ferrous fumarate (98.6 mg of elemental iron), and folic acid, which led to a dramatic rise in hemoglobin levels.

The innovation and crux of this study lies in the utilization of a school as the primary setting for an IDA intervention in a low-income community in India. While it is known that deworming tablets and vitamin supplementation can improve hemoglobin levels in IDA, the implementation of effective interventions requires further exploration of how to utilize existing community and social structures. Boarding schools such as Kaneria Boarding School are examples of community structures that hold high potential for such medical interventions. Previous studies have demonstrated the positive impacts of preventative health education implemented in schools in India. For example, dental health education amongst students aged 6–12 in India was shown to have improved oral health outcomes, including increased frequency of brushing and decreased oral plaque¹³. Similarly in this study, incorporating health education on IDA in schools holds promise in prevention against complications of IDA amongst children. Additionally, compliance rate and medication adherence is predicted to be higher in a school compared to in homes where children are reliant on themselves or their parents for supplementation. A study of compliance rates in Brazil showed that the two predominant factors preventing mothers from giving daily iron to their infants were signs of gastrointestinal intolerance and forgetfulness of the parent¹⁴. These factors can be eliminated in a school setting by providing direct patient health education on the side effects of iron supplementation as well as close monitoring of children by school workers or on site health professionals to ensure medication adherence.

The study benefited from a large sample size (n = 26,300 for the prevalence portion of the study) in addition to a relatively homogeneous population. Focusing on these key areas of India allowed the researchers to widely sample the population for children 0–18 and women 18–45. However, there are issues with the intervention taking place in a school setting rather than within the general village population. The results from the interventions taken in this study are only generalizable to school settings, not to an entire village’s population. The benefit of choosing one location is that it is more efficient in rolling out a certain public health intervention and ensuring compliance. The school setting allowed the researchers to better keep track of the individual participants and prevent loss to follow-up. Further study is needed to understanding how IDA interventions can be implemented in other existing social structures, such as religious hubs or local community centers.

Future study of the data will assess the relationship of hemoglobin levels and iron deficiency severity with specific socioeconomic factors, including caste, class, and working status. These future studies, in turn, would be able to guide the targeted deployment of vitamin B12, ferrous fumarate, and folic acid, and deworming tablets along with extensive educational intervention. Furthermore, more studies may be conducted on the relationship between early interventions in health and health literacy for young women and children from disadvantaged backgrounds and avoidance of downstream need for care.

Limitations of the study include the need to have a financial infrastructure in place in order to enact the multiple steps that were studied, including measuring hemoglobin levels and administering various interventions. The initial financial cost may be beneficial long term, but this would need to be the focus of a future longitudinal study. Additionally, the use of multiple medications as part of the intervention poses potential confounding variables, yet these methods were decided upon due to the lowered cost of administering the medications and vitamins together to all children within the intervention group. Future research opportunities may aim to individually administer each medication and study their unique effects on hemoglobin levels.

The study is also limited by its focus on the rural regions of India, and not in the urban areas. Within neighboring urban areas, iron deficiency anemia continues to remain an issue. Thus, future studies within nearby urban areas are necessary to look at the prevalence of iron deficiency anemia and enact similar interventions in order to assess whether urban areas have higher or lower response rates. Additionally, the findings of this study has potential to shape the evaluation and treatment of iron deficiency anemia in other countries, including the United States. Simple interventions involving medications and vitamins can potentially have profound effects in improving hemoglobin levels for women and children nationwide. Future studies will need to assess whether the iron deficiency anemia within the United States will respond similarly to the intervention used in Gujarat, India.

Furthermore, the effects of improving iron deficiency anemia can be evaluated using other forms of measure in addition to hemoglobin levels. For example, physical and mental health benefits such as improvement in concentration, increase in energy levels, and better educational outcomes amongst children can illustrate the direct impact of managing iron deficiency anemia on quality of life. Further studies comparing these factors pre and post intervention are needed.

This study shows that iron deficiency anemia continues to remain prevalent condition within rural villages of Gujurat, India. Hemoglobin levels collected from women and children show high levels of moderate to severe anemia, a public health crisis that must be addressed to prevent long term complications of iron deficiency. Medication and educational intervention utilizing the community structure of a boarding school reveals an significant increase on hemoglobin levels, holding potential for future interventions at pre-existing community structures such as schools, temples, and community centers. Important benefits in the utilization of community structures include the ability to provide extensive direct health education and monitor for medication adherence. Further study is needed to understand the impact of such interventions in urban areas and other countries, the implementation of a financial structure to support interventions, and the long term effects of intervention on mental and physical health.

IDA

Iron Deficiency Anemia

WHO

World Health Organization

Ethics approval and consent to participate: The University of California, Irvine Institutional Review Board determined the current study to be non-human subjects research because the data does not contain any identifying protective health information. The UCI Human Research Protections (HRP) staff states: “The Human Research Protections (HRP) staff reviewed the information submitted pertaining to your project ‘The Prevalence of Anemia in India - A Retrospective Study’ and concluded that the project, as described, does not qualify as human subjects research because the activities do not involve human subjects. Therefore, the research is not subject to UCI IRB review and approval.”
Consent for publication: Informed consent was obtained in this study. Students participating were given education on the medication interventions and blood samples, with the option to opt out of the study at any time.

Availability of data and materials: The datasets during and/or analyzed during the current study available from the corresponding author on reasonable request.

Competing interests: Amin reported serving as PI or co-I of clinical trials sponsored by NIH/NIAID, NeuroRx Pharma, Pulmotect, Blade Therapeutics, Novartis, Takeda, Humanigen, Eli Lilly, PTC Therapeutics, OctaPharma, Fulcrum Therapeutics, Alexion, unrelated to the present study; speaker and/or consultant for BMS, Pfizer, BI, Portola, Sunovion, Mylan, Salix, Alexion, AstraZeneca, Novartis, Nabriva, Paratek, Bayer, Tetraphase, Achogen LaJolla, Ferring, Seres, Millenium, Spero, Eli Lilly, PeraHealth, HeartRite, Aseptiscope, Sprightly, unrelated to the present study.

Funding: Not Applicable

Author’s contributions RB and AF analyzed and interpreted de-identified data regarding hemoglobin levels and intervention. SM, AA, DP, BK, RB, KB, and AA were major contributors in writing and editing the manuscript. All authors read and approved the final manuscript.

Acknowledgements: Not applicable

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No competing interests reported.

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Public Health Crisis of Anemia in India: Retrospective Study of Hemoglobin Levels and Impact of Medication Intervention in a School Setting

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