Iodine and Fluid Metabolism in Somali Women

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Iodine and Fluid Metabolism in Somali Women

A study of non-pregnant women 15-69 years in Hargeisa

MD Espen Heen

M.Phil Thesis

UNIVERSITETET I OSLO

31.01.2012

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Iodine and fluid metabolism in Somali women

A study of non-pregnant women 15-69 years in Hargeisa 2011

Supervisor: MD PhD Maria Romøren Co-supervisor: Msc PhD Ahmed Ali Madar Principal investigator: MD DTMH Espen Heen

Dean of medical faculty University of Hargeisa: Deria Ereg

Thesis submitted as a part of the Master of Philosophy Degree in International Community Health

Department of Community Medicine Institute of Health and Society

The Faculty of Medicine University of Oslo,

Jan 2012

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Iodine and Fluid Metabolism in Somali Women Espen K. Heen

http://www.duo.uio.no/

Trykk: Reprosentralen, Universitetet i Oslo

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Executive summary

The Somali population in the horn of Africa is one of the hardest affected by civil war, social unrest, draught and displacement in the African continent. Morbidity, age-specific mortality and malnutrition ratios are high and food diversity low. The first national Somali

micronutrient survey (2009) unexpectedly found “more than adequate” or “excessive” intake of iodine amongst women and children despite negligible usage of fish and iodized salt.

This study’s objective was to investigate how hydration status could affect estimates of iodine intake in non-pregnant women 15-69 years and to quantify the contribution of iodine intake from local water sources in this sub-population. Non-breastfeeding and breastfeeding women were the two main target-groups, the latter typically considered more susceptible for iodine deficiency.

A two stage, clustered, probability proportionate to size sampling with elements of purposeful re-sampling was applied to a cross-sectional study of women recruited through local non- governmental organizations across Hargeisa city. Demographic and anthropometric data were obtained through three structured interviews and measurements. Urine was collected over 24 hours, drinking water taken from homes and the iodine concentration in both fluids measured.

A drinking and voiding diary from the same 24 hours provided additional data of fluid metabolism.

Out of 160 women, 127 completed the whole study. 118 women were included in all analysis, 27 of which were breastfeeding. Demographic and SES characteristics of the women were close to a sample of urban Somaliland women from the MICS-3 study. Mean adjusted urine volume over 24 hours was 1.28 litres. There were high correlation between urine volume and recorded urine units voided (r = .873) and urine colour (rs = -.819). A median UIC of 125 µg/l was found. In the subsample of breastfeeding women, the result was 73 µg/l; indicating risk of mild iodine deficiency. Mean drinking volume over the same 24 hours was 2.04 litres. An independent drinking frequency questionnaire estimated a mean of 8.1 drink-servings per day.

90% of all fluids drunken came from local water sources. Public tap water and water from tanker trucks provided 95% of all plain water for drinks and food. The mean iodine

concentration in 49 water samples, from 4 different main water sources, was 51 µg/l. A three- fold difference (p<0.001) between the sources was found. A median iodine intake of 212 µg/d for breastfeeding women and 168 µg/d for non-breastfeeding women were estimated. We

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calculated proportion of iodine intake from main household water sources to be 55-70% of the total iodine intake in this latter group.

The study showed that the group of women had 10-15% smaller urine production than assumed in the reference material guiding the international recommendations for UIC levels in populations. The study also showed that the majority of iodine consumption originated from the women’s main water sources.

The authors recommend that UIC is being measured in a larger and representative sample of breast-feeding women in Hargeisa and that iodine concentration in main water sources for the city is being controlled in all seasons throughout the year.

National UIC estimates might hide large regional deviations due to different iodine levels from one water source to another. There is a need for better local estimates of iodine status in the Somaliland population.

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Preface

Iodine sustains life. Too little or too much iodine leads to disease, disability and

disfigurement. When iodine dynamics in a population is clarified, relatively simple means can re-establish health and strength. It is my hope that this report about iodine and fluid

metabolism in Somali women will contribute to a better understanding of the contingencies for iodine nutrition within Hargeisa and the wider Somaliland and ultimately lead to better or sustained health for women and infants in the future.

Espen K. Heen Hargeisa, 31.01.2012

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1 Acknowledgements

This research project and thesis would not have been completed without the help of many hardworking, dedicated and supportive people.

I want to express my gratitude to the two supervisors, Maria Romøren and Ahmed Ali Madar for their constant source of encouragement. Maria; your countless hours of voluntary work, discussing concepts, methodology and findings, has been beyond what any master-student could possibly dream of. There is a fingerprint of your improvements in every chapter.

Ahmed; with your background, you gave me courage to believe this project was possible, even in dark moments. Your ability to see the bigger picture has been of great help.

I want to thank Prof Gunnar Bjune, executive officer Line Løw and other staff at Section for International Health and Department of Community Health for their flexibility and support through this journey of almost four years.

An equal gratitude is directed to Øyvind Åsland, Elin Vannes, Berte-Stine Aas, Rune

Mjølhus, Anders Lilleheim, Nils Andreas Loland, Øystein Evjen Olsen and Tormod Helland in NLM, SMEA and NNM. You have all, at certain times, taken decisions to invest

organizational resources in this project. I hope you will be proud of what we have achieved together.

Amina A Mohamed, Bashe M Farah, Barkhad J Dagaal, Abdirahman O Jama, Hussein Ismail, Filsan H Mohamed, Amal A Yassin, Zuhuur M Abdi, Qabuul A Abdi, Nimo J Ali, Rahma M Absiiye, Hamda O Ali, Fathia Akli and Asia A Abdilahi: As project co-workers, translators, interviewers, drivers, logisticians, lab technicians and data entry clerks, you were the ones who carried out the project, and the quality of the data is there, only because of your hard work. I also want to thank the rest of the NNM team for encouragement and eagerness to help in times of need.

Special thanks go to Dean of medical faculty, Dr Deria Ereg, for representing the University of Hargeisa in this research collaboration, providing resources for the project. Many of the 24 medical students of 5th year, who were involved in the practical preparations of the field work, did important work. Their insight in the local context improved the design of the study in many ways.

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Prof Pieter Jooste and chief research technologist Emmerentia Strydom at NIRU, Medical research council, Cape Town, did a tremendous job with the analysis of water and urine samples. Your willingness to contribute with advice and suggestions has been highly appreciated.

Many people have supported the project with technical advice, pieces of information and logistic support. In particular I would like to thank the statisticians Lien Diep and Magne, Thoresen (UiO); the researchers Lawrence E. Armstrong (University of Connecticut) Gry I Granli (Rikshospitalet), Liv E Torheim (FAFO), Sigrun Henjum (HiA), Ismail AR Kassim (UN/CIHD)) Andrew Seal (CIHD); Olav Fredheim (NTNU); Prof Trond Markestad (UiB), As. Prof Sven Gudmund Hinderaker (UiB) and Øystein Evjen Olsen (UiB), Hospital director Edna Adan Ismail, geographical mapper Nasir B Ismail, capacity development officer Nura M Gureh (FSNAU), nutrition focal point Somaliland Fuad H Mohamed (FSNAU) and nutrition technical manager Grainne Moloney (FAO Somalia), water coordinator Hussein Gadain (FAO/SWALIM) and laboratory director Ahmed H Fara (HGH)

Human Care Diagnostics, MSF Belgium, THET Somaliland, United Basic Industries and World Courier all supported the project in various ways.

Without the eager support from the leaders of NAGAAD women umbrella Somaliland and the good collaboration with Hargeisa Voluntary Youth Committee (HAWOYOCO), Somaliland Women Organization (SOLWO), TAWAKAL in M. Mooge, Iftiin MCH and Edna Adan University Hospital MCH, the project would never have succeeded.

I want to express my gratitude to the Ministry of health, Somaliland for facilitating the project and for NORAD and Digni for ultimately providing the funding.

Eirin, Sunniva, Vemund and Ingjerd, my wife; you have paid a price for this piece of work. I am very proud of you. Thanks for doing this together with me!

Finally, I want to thank each of the 152 women who participated in the project, chose to bear the embarrassment and willingly exposed themselves in service for their fellow sisters.

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2 Abbreviations

BMI Body Mass Index

C Celsius degrees

CH Congenital hypothyroidism CI Confidence interval CV Coefficient of variation

CV Curriculum Vitae

DBS Dried blood spot DEFF Design effect

DIT Diiodotyrosyl

dl Decilitre

DTMH Diploma in Tropical Medicine and Hygiene EAR Estimated average requirements

FAO Food and Agriculture Organization FGC Female genital cutting

FGD Focus group discussion

FSNAU Food Security and Nutrition Analysis Unit – Somalia GAM Global Acute Malnutrition

GD Graves disease

GDP Gross domestic product GFR Glomerular filtration rate HcG Human choriogonadothropin ICC Intra cluster correlation

ICCIDD International council for the control of iodine deficiency disorders

ID Iodine deficiency

ID Identification

IDD Iodine deficiency disorder IDP Internally displaced person

IIH Iodine induced hyperthyroidism

INGO International non-governmental organisation LNGO Local non-governmental organisation

MCH Mother and child health (clinic) MICS Multi Indicator Cluster Survey

MIT Monoiodotyrosyl

ml Millilitre

mm Millimetre

MNAN Micro Nutrient and Anthropometric Nutrition survey MSc Master in Science

mU/l Milli Units per Litre

MUAC Mean upper arm circumference

NAGAAD Women LNGO umbrella in Somaliland NNM Nooleynta Naruurada Mustaqbalka (INGO) NORAD Norwegian agency for development cooperation NW North West (Somalia)

PhD Doctor of philosophy ppm Parts per million

PPS Probability proportionate to size

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µg/d Micrograms per day µg/l Micrograms per litre RBP Retinol binding protein

RDA Recommended daily allowance RDI Recommended daily intake SAC School aged children

SD Standard deviation SE Standard error of the mean SES Socio-economic-status SG Specific gravity

SK Sandell-Kolthoff (reaction) SPSS Statistical package for social sciences sTfR Soluble transferrin receptor

T3 Tri-jodothyronine

T4 Thyroxin

TAA Thyroid auto antibodies TAI Thyroid autoimmunity TALC Teaching aid at low cost

TG Thyroglobulin

TGR Total goitre rate

TPO Thyroperoxidase

TRH Thyrotropin releasing hormone TSH Thyroid stimulating hormone

U5 Under 5 years

UIC Urinary iodine concentration UIE Urinary iodine excretion UiO University of Oslo UL Upper tolerable level

UN United Nations

UNDP United Nations Development Program UNICEF The United Nations Children’s Fund WFP World Food Program

WHO World Health Organization

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3 Introduction

3.1 Geographical and anthropological context

The Horn of Africa

The Somalis is a remarkable African people, constituting the majority of the inhabitants in the eastern part of the Horn of Africa. This vast area comprises fully or partly six self-governing regions and four internationally recognized countries, namely Somalia, Djibouti, Ethiopia and Kenya. Estimates of the total population are quite imprecise, but looking at various national figures, 13-16 million people could be the reality.^1-4

The Somali people are traditionally a nomadic people of Cushitic origin, moving with their camels and goats over the grassy plains that constitute the vast area between the Ethiopian highlands and the Indian Ocean. Still, many of the nomads do not pay attention to borders, but follow the old routes in search for grass and water throughout the year.

From the earliest written documentaries, the Somali people have been described as a strong, tall and fearless people with a well-developed poetic tradition. Islam became the leading religious force between the 13th and 15th century.⁵ Traditionally, Sufism, a kind of religious brotherhood, has been a vital force within the Islamic community in this people. Today, 99 % of the population is officially Sunni-Muslims.⁶

The people within Somalia have been severely affected by political unrest and civil war, beginning in the eighties when the ruling President in the late republic, Siad Barre, increased his oppression of rivalling political and tribal leaders. Since 1991, the republic of Somalia with its 6-9 million inhabitants has been described as one of the few collapsing states in the world with no central government in charge of more than a minute fraction of its citizens. In the absence of central power; tribal, Islamic and opportunistic warlords have made space for their own governance, also affecting the regions around Somalia itself. Several international armed interventions have tried to stabilize the situation, but only added fuel to the fire.⁷ Unpredictable changes in the seasonal rain, deforestation and soil erosion have added to the war-made food shortage and created several famines in recent years. Hundreds of thousands Somalis have lost their lives. Millions of people have been forced to flee their homes and the

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numerous camps for refugees and internally displaced people (IDP’s) in the region are still growing.^8;9 The anarchistic everyday life have made the way open for exploitation of the vulnerable.

Somaliland

Somaliland is one of the six self-governed Somali regions on the Horn. Somaliland covers an area of approximately 137 000 km². The position for the eastern border is disputed.¹⁰

Somaliland was a British Protectorate from 1884 to 1960 after which the British Colonial Power withdrew from the area. Somaliland voluntarily merged with Somalia four days after independence and formed the Somali Republic. The present Somaliland has grown out of the ruins of the 1988- 1991 civil war and declared

independence from Somalia in 1991.⁶ Lack of international recognition has restricted bilateral support from the international community. Support has however been rendered through INGO’s and the UN of approximately

3-400 million dollars annually. According to UNDP estimates, the Somaliland Diaspora makes out the major source of financial income for Somaliland, amounting to approximately 700 million dollars annually.¹¹ Somaliland’s major export products are camel, goats and sheep.¹²

The inhabitants of Somaliland mainly consist of ethnic Somalis organized into three main clans. The total population is estimated to be between 1.5 - 3.5 mill.^1;4;10 The official figures indicate that 650 000 people are settled in the capital city of Hargeisa.¹⁰ The population is young with a broad-based population pyramid.¹³ More than 50% of the inhabitants are still considered nomadic or semi-nomadic.¹⁰

Map 1. Somaliland and its neighbour countries. Source: UN Department of peacekeeping operations, Jan 2007

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7 The terrain is broadly divided into three distinct landscapes: The lowlands along the northern coast (Guban), the east-west mountain ridge that are rising steeply up from the north reaching 2400 meter at its highest (Golis), and the highland plains that continue with falling altitude towards the Ethiopia and the south (Hawd).⁶

The climate varies from Semi-arid to desert with an average rainfall of 100-500 millimetre per year depending on the location.¹⁴ The temperature varies with the season. Hargeisa normally have temperatures between 25-35 °C in the middle of the day, night temperatures between 10- 25 °C. The western border area is the main agricultural district. Here, farms are growing maize, sorghum, millet, groundnuts, beans, root-vegetables, oranges, papaya and water melon.

3.2 Health and nutrition in Somaliland

Somaliland, like the rest of Somalia, has experienced huge challenges in providing health for their population since the collapse of the Somali state. There are obviously many factors that contribute to poor health in this region: Economic constrains, poor sanitation, low access to pure water, failing local food production, culture and tradition, low educational level and poor performance of the existing health care system. The latest published Multi Indicator Cluster Survey, MICS-3, revealed that both necessary basic conditions to facilitate health and preventive and curative health care services are scarce for parts of the population.¹³ MICS has a special focus on women and children.

Gender issues are contributing to poor health for women in Somaliland. Studies indicate that more than 90% of all fertile women have been infibulated.¹³ This is the most severe type of female genital cutting (FGC), contributing to women morbidity and neonatal mortality.

Like in other Somali regions, food security and nutrition is closely monitored by national and international stakeholders. Food and Agriculture Organization (FAO) to Somalia is operating a special Food Security Nutrition Analysis Unit

 1 in 7 children dies before the age of five.

 5% of children under the age of six months are exclusively breastfed

 3% receive all vaccines in the national program

 Only 10% received all four ANC visits recommended by WHO.

 80% of women give labour without skilled birth attendance

 1 in every 100 delivery gives a dead mother

Table 1. Mother and child health MICS-3, UNICEF Somalia 2006

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(FSNAU) with bi-yearly monitoring of the malnutrition situation and regular special surveys related to food and nutrition. Leaning on their reports, Somaliland has experienced 3-4 food crises in the last 10 years. The latest data available (Summer 2011) indicate that all the

regions of Somaliland experienced Global Acute Malnutrition (GAM) ratios of urban children between 7,1 and 13,8%, reaching a maximum of 23,2% in the hardest affected rural areas.¹⁵ A nutrition survey performed across whole Somaliland during 2009 showed high consumption of cereals, milk and milk products, oils and fats, and low consumption of vitamin C rich fruits, eggs, offal, legumes, nuts and fish.¹⁶ Amongst Internally displaced people (IDP’s) a survey in Hargeisa town in 2005 indicated that more than half of the population in question had consumed less than four food groups during the last 24 hours. Cereal staples, sugar /honey and fats/oil were the most commonly food items in use.¹⁷

3.3 Micronutrient status in Somaliland

Micronutrients are a diverse group of substances and elements that the body needs in very small quantities. Essential micronutrients are not synthesized or synthesized insufficiently by our cells biochemical machinery. Without proper consummation various physiological

mechanisms as energy production in the mitochondria, maturation of epithelium, immune and inflammatory responses, vision, bone growth, hormone production and mental development are affected. Iron, vitamin-A, zinc and iodine are considered the most important

micronutrients in public health interventions in developing countries.¹⁸

Before 2010, relatively little was known about the micronutrient status of the Somaliland inhabitants.

Vitamin A capsules had been regularly distributed to children in Somaliland, but assessment through mothers recall indicated coverage only around 25%.¹³ A survey performed by

UNICEF and the Ministry of health and Labour in Somaliland in 2001, looking at anaemia in children (<11g/dl) revealed a prevalence of around 60%, without being able to establish the cause thereof.¹⁹

This study focuses on iodine in Somaliland. No scientific publications about iodine status in the population within the borders of Somalia or Somaliland were possible to retrieve from the scientific databases Pubmed, Popline, Embase or Index Medicus (Feb 2009). MICS-3

described less than 1% of households using iodized salt, assessed through salt test kits.¹³

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9 There were also knowledge about patchy occurrence of goitre (neck swellings often linked to low iodine intake) in mountainous regions in the northern parts of Somalia (personal

communication, UNICEF office, Hargeisa), where also intake of sea food (high in iodine) is known to be low.¹⁷ Goitre rate in the population had not been systematically studied in any of the major surveys known to this author.

Micronutrients are cost effective interventions for health

Since rough estimated GDP in the area is low, between three- and six hundred dollars per capita,^20;21 cost-effectiveness should be a major focus when considering how to spend resources for health. A number of influential international health actors ^a have made estimations of cost-effectiveness for different health interventions in order to help poor countries and INGO`s prioritize potential health activities.

Even though there are different opinions about the methodologies in use and the research teams themselves acknowledge the many assumptions and uncertainties put into the

equations, at current, this is the best guides we have for how to spend resources on health, and they are worth looking into.

The 2008 Copenhagen Consensus report ranked micronutrient interventions as the single most effective way of using an extra 75 billion US dollars in low income countries over the next four years in competition with nine other interventions directed at different major global challenges. Some of the reasons that micronutrient projects have become so attractive to implement, is the fact that there might be a considerable loss in human productivity where substantial parts of the population suffer from sub-optimal intake. It is easy to administer and have a very low program cost per capita.

Ensuring an iodine-replete population is estimated to be a highly cost-effective intervention, yielding up to 70 times more back to the society than what it takes.^18;22

a The “Copenhagen consensus” meetings held in 2004 and 2008 have engaged numerous scientist and economists in debating how to allocate resources for health in the developing world. The “Disease Control Priorities Project” undertaken by The World Bank, the World Health Organization, and the Fogarty International Centre of the National Institutes of Health has a similar scope. WHO have established an own database called CHOICE with the scope of compiling evidence for the effect of different interventions under various contexts.

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Micronutrient update in the horn of Africa

The gap between the vast amount of knowledge about the importance of micronutrients and the lack of context specific knowledge, led FSNAU-Somalia and a number of collaborative partners to undertake the “National micronutrient and anthropometric nutrition survey

Somalia 2009” (MNAN survey). The survey included proxy measures of vitamin A, iron and iodine status for women and children in the population. The sample size was calculated to ensure valid data for Somaliland, in the study called the North West Zone. Iodine status was estimated through measuring iodine concentration in urine from research participants. Goitre rate and utilization of iodized salt was also included in the study. The hypothesis was to find deficiencies of all three micronutrients in the target population.¹⁶

The results of the MNAN survey were published in May 2010. The core results are displayed in the table below.

Table 2. Results from the MNAN survey indicating status of iron, vitamin-A and iodine in women and children.

Somaliland and Somalia 2009.

Indicator Sample North West (CI) Zones combined (CI)

Iron deficiency

5-59 months 59.6% (51.5-67.2) 58.9% (53.5-64.1)

SAC* 17.8% (13.0-24.0) 20.8% (16.9-25.4)

Non-pregnant women 15-49 years 39.0% (33.3-45.1) 41.5% (36.5-46.7)

Vit A deficiency

5-59 months 25.6% (18.3-34.5) 33.3% (27.5-39.6)

SAC* 21.3% (14.8-29.8) 31.9% (25.8-38.6)

Women 15-49 years 49.5% (43.3-55.6) 54.4% (48.3-60.4)

Median UIC SAC* 295.5 μg/l 417.1 μg/l

Non-pregnant women 15-49 years 224.4 μg/l 325.1 μg/l

Visible goitre prevalence Women 15-49 years 3.3% 2.0%

* School aged children

The study unexpectedly indicated a “more than adequate” or “excessive” intake of iodine in the population. Children had higher concentration of iodine in urine than women. For the other micronutrient indicators, there was high prevalence of deficiencies.

Iodine - what now?

The surprising iodine results were subject to vivid discussion. A number of actors voiced the possibility of chronic dehydration amongst the Somali population as an explanation for the high iodine concentration in urine. Hot weather, poor access to high quality drinking water and strenuous urination for many women with female genital cutting could make this scenario

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11 plausible. The estimation of iodine intake (deficiency, sufficiency, above requirements,

excessive) from UIC values assumes that an adult in average produces 1.5 litre urine per 24 hours.^23;24 An average urine output significantly less than 1.5 litre should also diminish the estimated iodine intake per 24 hours in the researched population.²⁵ If so, the urinary iodine concentration (UIC) results from the MNAN survey had to be understood in light of this uncertainty.

The current knowledge about low consumption of sea-food and iodized salt and the general knowledge about high mineral content of water in the region brought forward the hypothesis that drinking water is a major agent of iodine to the population.

3.4 Iodine in health and disease

3.4.1 Iodine in the natural world

Iodine is the fourth member of the halogens in the periodic system, characterized by high reactivity and unusual physical properties.²⁶ Iodine is a relatively scarce element in the surface layer of the earth representing a mean crustal concentration of 1.4mg/kg. The median concentration in soils around the world is 5mg/kg but with great variability.²⁷ Iodine is volatile and tends to be easily washed out of soil by water. Mountainous regions, areas previously under glaciers and valleys with flooding and rivers tend to be iodine poor.²⁸ The majority of available iodine is situated in the oceans in the form of iodide (I^-) and iodate (IO3), and a minor fraction is found in organo-bound substances. The average concentration in water is about 50 µg/l.²⁶ Iodine is brought back into soil and fresh waters mainly by evaporation of volatile organic iodine compounds that becomes part of precipitation.²⁹ Phytoplankton and seaweeds extract iodine from the sea in high concentrations and values up to 30 000 times the concentration in water has been measured.²⁶ They bring iodine into the marine food chain as food for sea-animals.

Finally, deposits of marine sediments are rich in iodine compounds. When such sediments ends up as aquifers under dry land, they might contribute to the composition of ground water where iodine is found mainly as part of humic substances. Depending on the molecular

weight and type, iodine bound to such substances have different bioavailability when ingested by human beings.³⁰

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Figure 1. Iodine-cycling in nature. From “Encyclopedia of Human Nutrition, 2^nd ed”²⁸

3.4.2 Sources of iodine in human nutrition

While most food and beverages contain iodine to some extent, their relative importance for human nutrition will vary greatly depending on the natural occurrence of iodine in soil, water and animal fodder in that particular region of interest . Seafood from salt water is the most reliable source of iodine, given the relative constant content of iodine in the oceans.³¹ Where the content of iodine in soil is high, cabbage and cereals tend to be a good source of iodine and meat from grazing animals will contain measurable concentrations of iodine.²⁸ Animal milk is an important source of iodine, since iodine is actively excreted from the lactating mammary glands.³² The content of iodine in surface water is usually very low, but ground water might contain high levels of iodine, as has been shown from a number of places around the world.^26;33-35 In such a situation, water might be the single most important determinant of iodine nutrition.³⁶

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13 3.4.3 The physiology of iodine^37;38

Iodine is, as far as we know, only strictly mandatory in the production of the thyroid hormones Tri-iodothyronine (T3) and thyroxin (T4) in the human body, although it is also present in saliva, gastric juice and sweat. The hormones do their actions in the nucleus of the cells as general gene expression regulators. They are involved in overall control of

metabolism, cell differentiation and maturation from the time of the tiny foetus throughout life.

Through food and beverage, iodine is absorbed by the intestine and brought as albumin bound iodid (I^-) to the thyroid gland with the blood stream. The highly vascular thyroid gland is the seat for T3 and T4 production. It is situated around the upper trachea between the

suprasternal notch and the thyroid cartilage, taking the shape of a butterfly. The thyroid gland consists of thousands of small follicles; minute spherical aggregations of specialized

endocrine cells (thyrocytes). The outside surface of the thyrocytes (basolateral) are surrounded by capillaries, the inner side (colloidal) constitutes a closed space where the thyrocytes excrete a substance called colloid. In the colloid, thyroglobulin (TG), a dimeric glycoprotein with numerous tyrosyl residues (tyrosin amino acid “arms”) are coupled with elemental iodine, forming monoiodotyrosyl (MIT) and diiodotyrosyl (DIT) residues which later aggregates into T3 and T4 like residues, still part of the vast thyroglobulin protein.

This is the storage form of the thyroid hormones. In

order to release the hormones into the blood stream, colloid is engulfed into the thyrocytes and the T3 and T4 released by an enzyme, together with MIT’s and DIT’s. Finally the T3 and T4 diffuse into the blood-stream, while the remains of the colloid are degraded and reused.

Figure 2. Chemical structure of Tyrosine and T4. From “Encyclo-pedia of Human Nutrition, 2^nd

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Figure 3. Illustration of the physiology of a thyroid follicle. From “Encyclopedia of Human Nutrition, 2^nd ed”

The whole process is regulated by the hypothalamus - pituitary gland – thyroid axis.

Hypothalamus, secreting thyrotropin releasing hormone (TRH) stimulates the pituitary thyrotrophic cells to excrete thyroid stimulating hormone (TSH) that is acting directly in speeding up the production and release of T3 and T4. At the glandular level, TSH increases the transport of iodine into the thyrocytes; the incorporation of iodine into thyroglobulin and the release of hormones from the colloid to the blood stream. This is done through activating a number of transport proteins and enzymes in the follicles.

In the situation where there is a balance of synthesis and need for thyroid hormones, T3 and T4 inhibit the pituitary and hypothalamus secretion of TSH and TRH in a classical inhibitory feed-back loop. A number of other hormones and high blood concentrations of iodide are able to inhibit the stimulus to or synthesis of the thyroid hormones. Some substances from the ingestion (goitrogens) like thiocyanate, perclorate, flavonoider, goitrin and humic substances are also able to inhibit the uptake or production of thyroid hormons.^39;40

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15 T4 is usually released to the blood stream in a ratio 40:1 comparatively to T3. More than 99%

is transported to the tissues bound to three different plasma-proteins. Inside the target cells, T4 is converted to T3 by the enzyme 5`deiodase. This, and the fact that T3 is 3-8 times more potent than T4, makes T3 the main acting hormone, leaving T4 more as a plasma reservoir of thyroid hormone. Certain tissues, like brain and brown fat, are able to locally regulate the activity of 5`deiodase. Finally, T3 is degraded by another, similar enzyme, called 5-deiodase, to reverse-T3 that is non-functional. This exhibits another means of controlling metabolism by the endocrine system.

3.4.4 Thyroid dysfunction

Looking at reference values in a certain population, abnormally low or high values of T3 and/or T4 measured in an individual are called hypo- or hyperthyroxinaemia. Low or high values of TSH is called hypo- or hyperthyroidism.³⁸

3.4.5 Iodine metabolism and recommendations for daily intake There is a vast body of literature and epidemiological research underlying the

recommendations of average daily iodine intake.^23;41-43 The recommendations, approved by WHO, is based on the understanding of the iodine metabolism in the body. Under steady state conditions, at least 90% of lost iodine is excreted through urine and the rest via feces.⁴⁴ Under profuse sweating, lactation and diarrhoea, the loss of iodine will be more complex.⁴⁵ In pregnancy there is a net accumulation and an increased loss of iodine during the 9 months, and that will affect the amount of iodine that pregnant women need each day.⁴⁶

Recommended daily allowance (RDA) or recommended nutrient intake (RNI) is a

recommendation for the individual and is based on estimated average requirements (EAR) in a population; the intake that is sufficient for 50% of a specific group, given by median values.

To calculate RDA or RNI from EAR, the value of 2 SD is added, now theoretically covering the needs of 97.5% of the population if requirements are normally distributed. When

comparing deficiency or sufficiency in populations, EAR is the correct reference for

comparison.⁴⁷ Since EAR relates to population medians of individual long term intake (usual intake), 24 hour intake measurement should be adjusted for intra-individual day-to-day variation. In general, the distribution curve of usual intake tend to be narrower than the corresponding distribution curve for 24 hour intake.⁴⁸

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Table 3. Recommendations for iodine intake (µg/day) by age and population groups. Source^41;47

Age or

population group

US Institute of Medicine*

US Institute of Medicine**

Age or

population group

World Health Organization***

Infants 0-12

months 110-130**** Children 0-5 yr 90

Children 1-8 yr 65 90

Children 9-13 yr 73 120 Children 6-12 yr 120

Adults ≥ 14 yr 95 150 Adults > 12 yr 150

Pregnancy 160 220 Pregnancy 250

Lactation 200 290 Lactation 250

*EAR **RDA. ***RNI. **** Adequate intake

3.4.6 Measurements of iodine status

The four common indicators for iodine status in individuals and populations are urinary iodine concentration (UIC), TG, TSH and goitre ratio. Each of the indicators has strengths and weaknesses in terms of what they can tell us. UIC is by far the most common indicator and is the only indicator used in most countrywide iodine assessment programs. Spot urine samples in an arbitrary time of day are the common way of collecting the urine species.

Because of large intra-individual day-to-day variation in urinary iodine excretion (UIE), UIC cannot be used to measure individual iodine status, but is a tool to identify iodine status in the population as a whole.⁴²

3.4.7 Iodine deficiency

Iodine deficiency (ID) describes the situation where the intake of iodine in an individual or a population is so low that physiological adaption starts to take place. ID manifested as clinical pathology is called iodine deficiency disorders (IDD). Many individuals will be able to maintain levels of T3 and T4 within the normal range, despite lower than recommended intake, playing on the described regulatory mechanisms. However, within a population, there are groups of more vulnerable individuals that are at high risk of IDD. The lower the average daily intake becomes, the bigger proportion of the population will become sick. Therefore, epidemiologists have categorized ID into three levels; mild, moderate and severe, each with a core set of operational definitions, in order to classify populations under study.⁴²

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Table 4. Indicators of iodine status in populations adapted from “Assessment of iodine deficiency disorders and monitoring their elimination, 2007”. ⁴²

Median Urinary Iodine

concentration (µg/l) Goitre ratio in Children 6-12 years (% of total target population)

Concentration of

Thyroglobulin in peripheral blood in children 5-14 years (µg/l)

Iodine status in target population

Children 6-12 years and non- pregnant women

Pregnant women

Excessive ≥300 ≥500

Above requirements 200-299 250-499

Adequate/normal 100-199 150-249 0.0-4.9% 4-40

Mild ID 50-99

< 150 is inadequate

5.0-19.9%

> 40

Moderate ID 20-49 20.0-29.9%

Severe ID < 20 30.0% or more

Many decades of epidemiological research has clearly pointed out the vulnerability to IDD for females in reproductive age and the very young from the beginning of second trimester to the third year of life.²⁵

The physiological changes in pregnancy with increased total T4 in plasma, transfer of T4 and iodine across the placenta and sometimes an increased UIE; augments the need for iodine with approximately 50% during first trimester compared with pre-gestational status.^46;49 During breastfeeding there is a continued high demand of iodine due to delivery of iodine through breast milk. Iodine loss between 75-200 micrograms per day (μg/d) have been

suggested⁵⁰ with average infant iodine needs between 90 and 110 μg/d⁵¹. Depending on iodine consumption, levels of stored iodine in the body, number of pregnancies and breastfeeding practises, a childbearing woman might gradually deplete her reservoirs.⁴⁶ While reservoirs are becoming empty, physiological adaptations to ID begins. Sub-clinical hypothyroidism

indicated by an increased TSH level,⁵² leads to slight hypertrophy of the thyroid tissue, eventually leading to diffuse goitre.⁵³ If the situation aggravates over time, multi-nodular colloid goitre might be the end result,⁴¹ leading to clinical hypothyroidism with typical manifestations like tiredness and lethargy, brittle hair, dry skin, puffy face, obstipation, reduced cognition and increased risk for miscarriages and stillbirths.^38;54;55 Similar mechanisms will occur when non-pregnant women, children and men develop IDD.

The consequences for the developing child are even more serious. Research both with animal models and with human beings show that T4 and T3 is necessary for appropriate neurological

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development between gestational week 12 and the first years of life. Low concentrations of thyroid hormones from the beginning of second trimester will impair auditory, motor, cognitive and physical development, cretinism being the ultimate syndrome for the hardest affected individuals in regions with severe ID.⁵³ As already stated, some will not survive the intra partum period at all. It is also postulated that neonatal mortality are increased in iodine depleted areas.⁵⁶

3.4.8 Iodine excess

While the knowledge of iodine deficiency has been growing steadily during the last hundred years, the risks of excess iodine intake have not been so clearly mapped. During the twentieth century, the main focus has been on iodine toxicity, where administration of several mg of iodine per day often has been the situation, either as part of an unusual diet, in treatment of hyperthyroidism, in exposure of iodine containing antiseptics and x-ray contrast fluids or by poorly controlled iodine fortification programs.^57;58 Quite recently the focus has been shifting to look at what happens in a population when there is intake between 300-1000 µg/d, and upper tolerable levels (UL) of average iodine intake in populations has been suggested. UL describes the maximum individual daily intake over time with almost no risk of harm.⁴⁴

Table 5. Cut-off levels for iodine excess and upper tolerable iodine intake levels in populations. ^41;42

Daily iodine intake (µg/day) Iodine status in target

population

Children 6-12

years Adults Pregnant and lactating women

Adequate 120 150 250*/290**

Iodine excess >300 - >500

Upper tolerable level >300 >600*/1100** >600*/1100**

*WHO and ** Institute of medicine (United States) have different recommendations

Research has shown that average iodine consumption of more than upper tolerable intake over months reduces the level of T4 and increase the risk of goitre. In fact, excess iodine has the ability to inhibit thyroid function.⁵⁹ Even in iodine sufficient areas (no deficiency, no excess), we see more overt hypothyroidism, more thyrotoxicosis and more autoimmune thyroid illness than in mild iodine deficient areas.⁴¹ This trend will increase as the iodine load in the

population increases.

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19 Mechanisms and manifestations of thyroid diseases are slightly different depending on the nature of iodine excess in the population. In areas with high iodine intake over decennia, people with healthy thyroid glands will easily handle excessive iodine intake by a variety of protection mechanisms.⁵⁸ However, a higher iodine load over time is a risk factor for development of thyroiditis leading to hypothyroidism (subclinical and clinical; increase of TSH level).⁶⁰ If pregnant mothers develop such a condition, this will also affect the foetus.

Iodized TG seems to be more immunogenic than plain TG and higher iodine concentrations in the thyroid might lead to higher radical load, both through iodine itself and through hydrogen peroxide formation.⁵⁹ Another sub-group are at risk of developing Graves’ disease (GD) at a rather young age, subsequently leading to hyperthyroidism.⁶¹ This is only documented firmly from studies in Europe where it seems like GD mainly is a hereditary condition, but iodine triggers or hastens the development of the disease.⁶² In areas with iodine excess, diffuse goitre caused by autoimmunity or increased TSH level might be seen already in children. A few studies indicate that increased thyroid gland size in school aged children (SAC) 6-12 years starts around an average UIC of 500 µg/l.^34;63

In areas where high iodine intake represents a transient or relatively new situation from a baseline/background of iodine deficiency, we would expect more nodular goitre, increasing the risk of iodine induced hyperthyroidism (IIH) with potentially severe consequences for the individual. We would also expect to see increased incidence of thyroid autoimmunity.⁶¹

3.4.9 Summary

Studies from the last 20 years indicate a U-shaped relationship between average iodine intake in the population and the individual’s risk of developing thyroid disease. The optimal average iodine intake has a rather narrow range in order to balance the risk of ID towards the risk of iodine excess.⁶¹ This optimal range will be slightly different in populations around the world due to variation in genetics, bioavailability of iodine ingested, temporal variations in iodine exposure and type and concentration of goitrogens present in the typical daily diet.

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4 Objectives in the study

The researchers of the MNAN study recommended further investigation into the causes of the high levels of iodine in urine from women and children in Somalia. In line with their research recommendations, the objectives of this study are:

To investigate if dehydration amongst study participants could affect the estimates of iodine intake in this particular population.

To identify the sources of ingested iodine, particularly if drinking water could be an explanation for high iodine intake.

Primary research questions in this study of non-pregnant women aged 15-69 years

What is the mean volume of urine produced in 24 hours?

What is the average fluid intake in the same 24 hours?

What is the median urinary iodine concentration (UIC) from 24 hour urine collection?

What proportion of ingested iodine can be explained by the iodine content in the research participant’s drinking water sources?

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5 Subjects and methods

5.1 Study design

This is a cross-sectional study of women aged 15-69 years recruited through local non-

governmental organizations in Hargeisa city. A two stage, clustered, probability proportionate to size sampling with elements of purposeful re-sampling was applied. Demographic and nutritional data were collected through three structured interviews and anthropometric measurements. Urine was collected over 24 hours and drinking water taken from homes. A drinking and voiding diary from the same 24 hours provided additional fluid metabolism data.

Module III

•Ready?

•Various

•Household

•Anthropo

Instruction

•Explaining collection and logs

•pratical training

Module IV

•Drinking and voiding habits

•Water

•Various Q

•medicines

•Urine vol

•Lab analysis

•Urine transferred to vials

Module I

•Consent

•Demographic data

•Exclution

•Age and para

Consent info

•Explaining the whole study

•Exclution

•Bodily function problems

Module II

•Exclution

•disease

•medicines

•iodine

•Consent

•Preparing next meeting

First interview, day 1

Second interview, day 2 Third interview, day 3

24h trial

Figure 4. Illustration of the flow of field trial and data collection at each interview. Iodine and fluid metabolism in Somali women.

Hargeisa May-June 2011

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5.2 Development of data collection tools

5.2.1 Questionnaire

Variables of importance to the research objectives; for identifying exclusion criteria and for quality control of data collection were identified. Questions chosen were guided by pre- existing, tested questionnaires.13;16;64;65 After developing the first draft of the questionnaire in English, the wording and order of the questions were modified stepwise through focus group discussions (FGD) with Somali senior medical students, nurses and medical doctors, looking at cultural aspects, relevancy and saturation. Each question was given a unique alphanumeric 3 digit code. The questionnaire was reorganized thematically, and split in four modules and eight sections in order to fit the organization of the field trial.

Table 6. Questionnaire modules, sections and variable names. Iodine and fluid metabolism in Somali women.

Hargeisa May-June 2011

Separate questionnaires Section Question Code and Range Module I and II Demographic data

Exclusion criteria

DD00-DD21 E1-E24

Module III ^Checklist

Various questions Household Anthropometry

C1-C15 W1-W9 HH5-HH17 M1-M3

Module IV Drinking and voiding habits Water and Sanitation Various questions Checklist

U1-U20 WS1-12 W10-14 C18

The four modules were translated from English to Somali, using a team of five. One male medical doctor (A) and one female project manager (B) had Somali as mother tongue and were fluent in English. Two females, a medical doctor (C) and a nutritionist (D), had English as mother tongue and were fluent in Somali. Finally, the principal investigator, who was fluent in English and had basic skills in Somali (E). Each module was independently translated by two members; A, C or D. For each question, the two translations were

compared, technical input given by E, and a mediator (B) negotiated till a joint translation of the question was reached. For some questions, drafts of the MICS-4 (2011) study questions in

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23 Somali translation were consulted and adopted if appropriate. An independent person was used to improve orthography. The translated version of the questionnaire was piloted on three groups of Somali medical students and nurses and feed-back led to minor corrections. Finally, a standard layout for the four modules was incorporated, including colour and font codes and skip instructions in the margin to make it easier for the research assistants to standardize their interviews. The questionnaires in Somali and English language can be found in attachments I and J.

5.2.2 Drinking and voiding memos

To validate the collected urine volumes from the women¸ triangulation through detailed interviews of drinking and voiding habits during the 24 hour trial was desirable. Two different memory tools were developed for the women:

Paper-log

A paper form with icons for fluid intake and voiding frequency/volume was used by literate women and for the interviewers in order to structure the drinking and voiding data. (See paragraph 5.11.3. for further explanation)

Box-log

A small, clear plastic box with lid and two small zip bags containing 20 yellow paper balls and 20 blue paper-strips were given to illiterate women. Each time the woman drank, she placed one or more paper-strips in the box, guided by defined rules. For each void, 1-3 yellow paper balls were placed in the box defined by the volume she voided.

A detailed description of the development of the memo-tools can be found in attachment C.

5.2.3 Fluid volume models

In the interview setting, detailed records of type and volume of each “drink” during the 24 hour trial was done. Two different aids were developed to ease communication between the women and the interviewers and increase the reliability of the drinking volume

measurements:

Iodine and Fluid Metabolism in Somali Women

Iodine and Fluid Metabolism in Somali Women

A study of non-pregnant women 15-69 years in Hargeisa

MD Espen Heen

M.Phil Thesis

UNIVERSITETET I OSLO

Iodine and fluid metabolism in Somali women

A study of non-pregnant women 15-69 years in Hargeisa 2011

Department of Community Medicine Institute of Health and Society

The Faculty of Medicine University of Oslo,

Jan 2012

Executive summary

Preface

Table of contents

1 Acknowledgements

2 Abbreviations

3 Introduction

3.1 Geographical and anthropological context

3.2 Health and nutrition in Somaliland

3.3 Micronutrient status in Somaliland

3.4 Iodine in health and disease

4 Objectives in the study

5 Subjects and methods

5.1 Study design

Module I

5.2 Development of data collection tools