Epidemiology of Iodine Deficiency Disorders in Pakistan ...with spectrophotometric detection. The inter-assay coefficient of variation (CV) was calculated to be 5.6%. Evaluation of

I

From the Institute for Community Medicine, Department SHIP/ Clinical-Epidemiological

Research

Director: Prof. Dr. Henry Völzke

Of the Faculty of Medicine, University Medicine Greifswald

Epidemiology of Iodine Deficiency Disorders in Pakistan and North-

East Germany

Inaugural – Dissertation

to

Attainment of Academic Grades

in

Doctor of Natural Sciences in Medicine

(Dr.rer.med)

from

Faculty of Medicine

of

University Medicine Greifswald

2017

Presented by: Rehman Mehmood Khattak

born on: 07 January 1979

in: Karak, Pakistan

II

Dean: Prof. Dr. Max P. Baur

1. Expert: Prof. Dr. Henry Völzke

2. Expert: Prof. Dr. D. Rothenbacher

3. Expert: Prof. Dr. Thomas Remer

City, Room: , Greifswald

Day of Defence: 26 March, 2018

III

Table of Contents

1. Introduction ......................................................................................................................... 1

1.1. Iodine Deficiency Disorders ............................................................................................. 1

1.2. IDD in Pakistan ................................................................................................................ 1

1.3. IDD in North-East Germany ............................................................................................ 2

2. Methodology ......................................................................................................................... 3

2.1. Study Design and Subjects. .............................................................................................. 3

2.1.1. Pregnant Women Study Population ........................................................................... 3

2.1.2. SHIP Study Population ............................................................................................. 3

2.2. Exclusion Criteria ............................................................................................................ 3

2.3. Assessments in Pregnant Women Population ................................................................... 4

2.4. Assessments in the SHIP Population ................................................................................ 4

2.5. Thyroid Ultrasound .......................................................................................................... 5

2.6. Statistical Analysis ........................................................................................................... 6

3. Results .................................................................................................................................. 6

3.1. Iodine Nutrition in Pregnant Women and Regional Influence in Pakistan ......................... 6

3.2. Monitoring the Prevalence of Thryoid Disorders in North-East Germany ......................... 8

4. Discussion ........................................................................................................................... 10

4.1. Iodine Nutrition in Pregnant Women and Regional Influence ......................................... 10

4.2. Monitoring the Prevalence of Thryoid Disorders in North-East Germany ....................... 11

4.3. The Common Lessons .................................................................................................... 12

4.4. Strengths and Limitations ............................................................................................... 14

5. Conclusion .......................................................................................................................... 14

6. Literature Cited ................................................................................................................. 15

IV

7. Scientific work .................................................................................................................... 20

7.1. Regional Influence on Iodine Nutritional Status of Pakistani Pregnant Women .............. 20

7.2. Monitoring the Prevalence of Thyroid Disorders in the Adult Population of Northeast

Germany ................................................................................................................................... 46

7.3. Factor Affecting Sustainable Iodine Deficiency Elimination in Pakistan: A Global

Perspective ............................................................................................................................... 58

8. Appendix ............................................................................................................................ 68

A. Statutory Declaration ..................................................................................................... 68

B. Own Contributions ......................................................................................................... 69

C. Curriculum Vitae ........................................................................................................... 70

D. Scientific Output ............................................................................................................ 71

E. Acknowledgements .............................................................................................................. 74

v

List of Tables

Table 1. Association of Demographic Characteristics with Iodized Salt Intake, Goiter

Prevalence and UIC <150 µg/L…………………………………………………………........7

Table 2. Change in Thyroid Characteristics between SHIP-0 (1997 - 2001) and SHIP-Trend-

0 (2008 - 2012) ......................................................................................................................9

Figure 1. Adjusted Association of Urban-rural Distribution to Various Parameters of Iodine

Deficiency .............................................................................................................................7

1

1. Introduction

1.1. Iodine Deficiency Disorders

Iodine deficiency disorders (IDD) result from insufficient iodine intake, and may lead to many

adverse effects on growth, development and thyroid diseases in humans (1). The nature of IDD is

variable depending on the region, iodine supplementation, stage of life and physiological

prospects (2).

Goiter presents the classic sequel of chronic iodine deficiency (3). When the iodine intake

decreases, the secretion of the thyroid-stimulating hormone (TSH) is enhanced for the reason to

increase the uptake of available iodine. TSH concentrations in turn stimulate hypertrophy and

hyperplasia of the thyroid, resulting in goiter. Initially goiters are characterized by diffuse,

homogeneous enlargements, but over time nodules and (subclinical) hyperthyroidism often

develop in adults.

Fetal damage is considered as the most serious adverse effect of iodine deficiency (3).

Insufficient iodine supply to the fetus impairs brain development (3). Severe iodine deficiency

during pregnancy may also result in stillbirths, abortions, and congenital abnormalities (4,5).

1.2. IDD in Pakistan

Pakistan is a country with history of iodine deficiency (6). McCarrison firstly identified the

region as severely iodine deficient in 1908 (7). Since then almost all the studies reported a high

goiter prevalence and iodine deficiency particularly in the Khyber Pakhtunkhwa (KPK) province

of Pakistan (6). Pakistan formally adopted the universal salt iodization programme in 1994.

These efforts resulted in a decline of iodine deficiency up to 50% (8). However, the estimated

improvement in IDD eradication is not uniform and may be over-estimated (6). The major

reasons for this are lack of proper planning, political will, and monitoring as well as myths

regarding iodized salt and socioeconomics (6).

Apart from others− Pakistani society is exposed to rural/urban disparity (9) and gender

discrimination (10). When on one hand urban populations enjoy more livelihood facilitation (9),

on the hand females are exposed to direct neglect in the society in terms of exposure, equality

2

and socioeconomic opportunities (10). Women in pregnancy are considered as the most affected

group for iodine deficiency because more iodine is needed during pregnancy (11). In Pakistan

there is less awareness and intake of iodized salt in the general population, as well as no

systematic adaptation of iodine supplementation to pregnant women (6). Hence females are more

exposed to the iodine deficiency issues in Pakistan, while the regional influence work

simultaneously.

1.3. IDD in North-East Germany

Before reunification both parts of Germany were iodine deficient. In the Eastern part, however,

due to mandatory iodine prophylaxis adaptation in 1983, the iodine status of the population

improved from moderate to mild iodine deficiency. After the reunification of Germany in 1989

“voluntary principle” was adopted leading again to a decrease in iodine intake (5). After

improving the legislation of the voluntary iodine fortification programme in 1993, the urinary

iodine excretion levels were elevated and goiter prevalence decreased (12,13). The North-East

German population demonstrated major consequences of long-term iodine deficiency in adults; a

high prevalence of goiter, thyroid nodules and hyperthyroidism in general population, as

extracted from the results of first Study of Health in Pomerania cohort (SHIP-0) conducted

between 1997 to 2001 (14).

A stable IDD prevention would result in a decrease of IDD without increase in the prevalence of

hypothyroidism and autoimmune thyroid disorders (15). The continuously improved iodine

status in North-East German population was reflected by the five-year follow-up examinations of

SHIP; showing a reduction of goiter, thyroid nodules and hyperthyroidism. Likewise, a decrease

in the incidence of positive autoantibodies to thyroperoxidase (anti-TPO Abs) was observed (16).

Germany and Pakistan present different socioeconomics, cultural values and adaptations to the

IDD eradication but have resemblance in history of iodine deficiency. In the recent years

Germany has improved in IDD eradication more than Pakistan. The purpose of this research was

to study the regional influence on iodine nutritional status of pregnant women in Pakistan and to

monitor the effectiveness of the iodine fortification programme in the North-East German

population.

3

2. Methodology

Our results are based on cross-sectional data obtained from pregnant women in the KPK

province of Pakistan and from the general population of a population based study SHIP− in the

North-East of Germany

2.1. Study Design and Subjects.

2.1.1. Pregnant Women Study Population

Pregnant women data was obtained from randomly selected (public and private) prenatal clinics

in five districts of the KPK province of Pakistan. Women visited there for their routine checkup

between March and September 2012. Data were obtained from almost 250 pregnant women from

each district reaching to a total of 1260 in all five districts.

2.1.2. SHIP Study Population

The SHIP project consists of two population-based cohorts, for which only individuals with

German citizenship and main residency in the study area were recruited. (17) In the first SHIP

cohort; SHIP-0, individuals aged 20-79 years were selected from population registries by a two-

stage cluster sampling method. The net sample (without migrated or deceased persons)

comprised 6265 eligible subjects, of which 4308 (response 68.8%) participated between 1997

and 2001. A separate stratified random sample of 8826 adults aged 20-79 years was drawn for

SHIP-Trend, of which 4420 subjects participated between 2008 and 2012 (response 50.1%) in

SHIP-Trend-0.

All participants gave written informed consent before data collection for pregnant women and

SHIP data. The SHIP study conformed to the ethical guidelines of the Declaration of Helsinki as

reflected in a priori approval by the local ethics committee of the University of Greifswald, while

for the pregnant women study an institutional approval from the academic research committee of

Kohat University of Science and Technology (KUST), Kohat, Pakistan was obtained.

2.2. Exclusion Criteria

Pregnant women with self-reported chronic medical disorders were not included in the study.

The study population available for the final analysis consisted of 1246 pregnant women.

4

For the analysis of monitoring trend of thyroid diseases in SHIP, 36 individuals were excluded

from analysis in SHIP-0 and 13 in SHIP-Trend-0 because of missing data regarding diagnosed

thyroid disorders.

2.3. Assessments in Pregnant Women Population

All the pregnant women were asked to complete a short interview questionnaire containing the

information related to sources and reasons for intake and non-intake of iodized salt. The

questionnaire also comprised questions related to knowledge of iodized salt nutrition.

Information on the number of previous pregnancies and/or abortions (fetal loss due to various

reasons, not including voluntary termination of pregnancy) was also obtained.

The gestational age of the pregnant women was determined from the first day of the last regular

menstrual period with gestational ages of ≤14.9, 28.9, and ≥29 weeks comprising the first,

second, and third trimesters of pregnancy, respectively.

For goiter assessment in pregnant women the WHO/UNICEF/IGN recommended palpation

method was used (18). UIC was measured using a modification of the Sandell-Kolthoff reaction

with spectrophotometric detection. The inter-assay coefficient of variation (CV) was calculated

to be 5.6%. Evaluation of group iodine status was based on median UIC categories defined by

the WHO/IGN (19). These are: recommended – median 150-249 μg/L; mild iodine deficiency –

median <150 μg/L.

2.4. Assessments in the SHIP Population

For the analysis of monitoring trends of thyroid diseases in SHIP, diagnosed thyroid disorders

were assessed by computer-assisted personal interviews. All participants were asked to bring

their medications taken seven days prior to the time of examination. Medication data were

obtained online using the IDOM program (online drug-database leaded medication assessment)

and classified according to the Anatomical-Therapeutic-Chemical (ATC) classification system

(17).

In SHIP population goiter assessment was based on thyroid volume determined with

ultrasonography. Goiter was defined as a thyroid volume exceeding 18 mL in women and 25 mL

in men (20). Urinary iodine concentrations were measured from spot urine samples by a

5

photometric procedure (Photometer ECOM 6122, Eppendorf, Hamburg, Germany) with Sandell

and Kolthoff reaction. The inter-assay coefficient of variation (CV) was calculated to be 5.6%.

Urinary creatinine concentrations were determined with the Jaffé method (SHIP-0: Hitachi 717,

Roche Diagnostics, Germany; SHIP-Trend-0: Dimension Vista, Siemens Healthcare Diagnostics,

Eschborn, Germany). Evaluation of group iodine status was based on median UIC categories

defined by the WHO/IGN (18). The iodine/creatinine ratio was calculated by dividing urinary

iodine by urinary creatinine concentrations.

Serum TSH, fT3, fT4 levels in SHIP study were measured by an immunochemiluminescent

procedure (SHIP-0: LIA-mat, Byk Sangtec Diagnostica GmbH, Frankfurt, Germany; SHIP-

Trend-0: Dimension Vista, Siemens, Eschborn, Germany). The functional sensitivity of the TSH

assay was 0.03 mIU/L (21) for SHIP-0 and 0.005 mIU/L for SHIP-Trend-0 (22). For SHIP-0

coefficients of variation for TSH were 5.0% at 0.3 mIU/L, 3.7% at 16.1 mIU/l, while for SHIP-

Trend-0 these were 2.04% or 2.20% for TSH. A method comparison between the two TSH

laboratory methods showed only negligible differences (23). High and low serum TSH levels

were based on the reference range established from data for SHIP-0 (0.25 mIU/L - 2.12 mIU/L)

and SHIP-TREND-0 (0.49 mIU/L - 3.29 mIU/L) respectively (21,22).

Anti-TPO Abs were measured by an enzyme immunoassay in the whole SHIP study

(VARELISA, Elias Medizintechnik GmbH, Freiburg, Germany). The functional sensitivity of

this assay was 1 IU/ml, and the coefficient of variation over the whole study period was 12%.

The anti-TPO Abs status was defined as follows: normal < 60 IU/ml in men and < 100 IU/ml in

women; increased > 60 IU/ml in men and > 100 IU/ml in women; positive: > 200 IU/ml in both

sexes (24).

2.5. Thyroid Ultrasound

Thyroid ultrasonography was performed in SHIP-0 using an ultrasound VST-Gateway with a 5

MHz linear array transducer (Diasonics, Santa Clara, CA, USA). In SHIP-Trend-0

ultrasonography was performed with a portable device using a 13-MHz linear array transducer

(Vivid-I, General Electrics, Frankfurt, Germany). In both studies intra- and inter-observer

reliabilities were assessed before the start of the study and semi-annually during the study. For

thyroid volume all inter-observer and inter-device variabilities showed mean differences (±2 SD)

6

of < 5% (<25%) (25). Thyroid volume was calculated as length x width x depth x 0.479 (ml) for

each lobe (26). The normal thyroid echo pattern was classified as homogeneous. A homogeneous

echo pattern with reduced echogenicity was defined as hypoechogenic. Nodular changes

exceeding 10 mm in diameter were defined as thyroid nodules.

2.6. Statistical Analysis

Multivariable logistic regression analysis adjusting for age was used to regress the outcome

measures (knowledge about IDD, iodized salt intake, UIC <150mIU/L and goiter prevalence) on

regional influences (as exposure) in each specific district. These results are presented as odd

ratios and their 95% confidence interval.

For the analysis in SHIP, all analyses were standardized by base-weights to account for different

sampling probabilities. In SHIP-Trend-0, additionally, inverse probability weights for study

participation were calculated, which were multiplied with the base-weights. Differences in

median levels between SHIP-0 and SHIP-Trend-0 were tested by median regression models;

prevalence differences between SHIP-0 and SHIP-Trend-0 were tested by Poisson regression

models.

A p-value of <0.05 was considered statistically significant. All analyses were carried out with

Stata 13.1 and 11.2 (Stata Corporation, College Station, TX, USA).

3. Results

3.1. Iodine Nutrition in Pregnant Women and Regional Influence in Pakistan

The majority of pregnant women (88.0%) had no knowledge about IDD (Table 1). A very high

(79%) percentage of pregnant women were not taking iodized salt, out of which 36.6% reported

that iodized salt would negatively affect reproduction and for 17.0%, it was too expensive.

Iodized salt intake in pregnant women was high in the big cities (Peshawar, Nowshehra) and in

the urban areas (27.0%) (Table 1).

7

Table 1. Association of Demographic Characteristics with Iodized Salt Intake, Goiter

Prevalence and UIC <150 µg/L

Characteristic

N=

1246

Iodized salt intake

(n=262; 21.0%)

Goiter prevalence

(n=318; 25.5%)

UIC <150 µg/L

(n=731; 58.7%)

n n (%) P value n (%) P value n (%) P value

District

Lakki

Marwat 244

45 18.4 0.64

44 18.0 0.656

57 23.4 0.096

Karak 252 9 3.6 <0.001 111 44.1 <0.000 208 82.5 <0.001

Kohat 249 27 10.8 <0.001 54 21.7 0.565 165 66.3 <0.001

Nowshehra 251 68 27.1 <0.001 60 23.9 0.244 226 90.0 <0.001

Peshawar 250 113 45.2 Ref 49 19.6 Ref 75 30.0 Ref

Residence

Rural 783 137 17.5 <0.001

209 26.7 0.218

467 59.6 0.364

Urban 463 125 27.0 109 23.5 264 57.0

Knowledge

about IDD

No 1093 147 13.5 <0.001

290 26.5 0.030

659 60.3 0.002

Yes 153 115 75.2 28 18.3 72 47.1

P-value calculated from logistic regression, adjusted for age, (Ref = reference category)

Figure 1. Adjusted Association of Urban-rural Distribution to Various Parameters of Iodine

Deficiency

8

In 41.3% of the pregnant women, we observed a UIC of >150mIU/L. The median UIC level for

the pregnant women was 131µg/L. The total goiter prevalence in pregnant women was 25.5%.

The prevalence of UIC <150mIU/L in pregnant women did not differ between rural and urban

areas (Table 1). The results based on logistic regression analysis shows that the prevalence on

knowledge about IDD, iodized salt intake, UIC <150mIU/L, and goiter did not differ in pregnant

women between urban and rural areas (Figure 1). In district Lakki Marwat except, the pregnant

women from urban residence had higher odds of having knowledge on IDD and iodized salt

intake than their rural counterparts.

3.2. Monitoring the Prevalence of Thryoid Disorders in North-East Germany

The prevalence of diagnosed thyroid disorders increased from 7.6% [CI 6.9-8.5] in SHIP-0 to

18.9% [CI 17.6-20.1] in SHIP-Trend-0 (Table 2). Likewise, the prevalence of thyroid medication

intake increased from 6.2% [CI 5.5-7.0] to 11.1% [CI 10.1-12.2]. The median urinary iodine

excretion levels decreased significantly, which was more pronounced in females than in males

(Table 2). The median iodine-to-creatinine ratio declined in all sex- and age-groups with stronger

decrease in females than in males. The prevalence of median urinary iodine excretion levels

<100µg/L increased between SHIP-0 and SHIP-Trend-0 (Table 2). Median serum TSH levels

increased significantly between SHIP-0 and SHIP-Trend-0, resulting in a right shift of the serum

TSH level distribution (Table2). The prevalence of high serum TSH levels remained almost

stable between SHIP-0 and SHIP-Trend-0. Likewise, the prevalence of low TSH remained

almost stable between SHIP-0 and SHIP-Trend-0. The prevalence of increased anti-TPO Abs

and positive anti-TPO Abs decreased from SHIP-0 to SHIP-Trend-0 in the whole study

population (Table 2). The prevalence of hypoechogenic thyroid pattern decreased from SHIP-0

to SHIP-Trend-0 (Table 2). The median thyroid volume remained similar between SHIP-0 and

SHIP-Trend-0 in the whole study population (Table 2). Goiter prevalence decreased

significantly; more pronounced in males than in females, while the prevalence of thyroid nodules

increased between SHIP-0 and SHIP-Trend-0.

9

Table 2. Change in Thyroid Characteristics between SHIP-0 (1997 - 2001) and SHIP-Trend-0 (2008 - 2012)

All Males Females

SHIP-0 SHIP-Trend-0 p* SHIP-0 SHIP-Trend-0 p* SHIP-0 SHIP-Trend-0 p*

Iodine; µg/l 123.0 (122.5; 123.5) 112.0 (111.5; 112.5) <0.001 134.0 (133.2; 134.8) 126.0 (125.5; 126.5) <0.001 108.0 (107.2; 108.8) 91.9 (91.4; 92.4) <0.001

Iodine to creatinine ratio;

µg/g 130.1 (129.8; 130.4) 113.7 (113.3; 114.0) <0.001 116.2 (115.7; 116.8) 105.8 (105.4; 106.2) <0.001 152.2 (151.4; 153.0) 128.0 (127.2; 128.8) <0.001

Iodine < 100 µg/L; % 37.7 (36.0; 39.5) 43.9 (42.0; 45.7) <0.001 30.5 (28.2; 32.9) 36.2 (33.9; 38.6) 0.001 45.6 (43.0; 48.3) 53.8 (51.0; 56.6) <0.001

Thyroid volume, ml 18.41 (18.36; 18.46) 18.27 (18.24; 18.30) <0.001 21.79 (21.71; 21.87) 20.39 (20.35; 20.44) <0.001 15.31 (15.26; 15.36) 15.43 (15.40; 15.47) <0.001

Goiter; % 35.1 (33.5; 36.7) 29.4 (27.8; 31.0) <0.001 36.5 (34.2; 38.8) 26.6 (24.7; 28.7) <0.001 33.7 (31.5; 36.0) 32.9 (30.4; 35.6) 0.676

Thyroid nodules; % 18.5 (17.3; 19.8) 30.5 (29.0; 32.1) <0.001 14.8 (13.2; 16.7) 24.4 (22.5; 26.4) <0.001 22.5 (20.7; 24.3) 38.4 (35.9; 41.0) <0.001

Hypoechogenic thyroid

pattern; % 5.4 (4.8; 6.2) 3.7 (3.1; 4.4) 0.001 1.8 (1.3; 2.4) 2.6 (1.9; 3.4) 0.113 9.5 (8.1; 11.0) 5.2 (4.1; 6.5) <0.001

Increased anti-TPO

antibodies; % 6.7 (5.8; 7.6) 5.2 (4.5; 6.0) 0.013 3.7 (2.9; 4.8) 3.7 (2.9; 4.7) 0.994 9.9 (8.5; 11.5) 7.1 (5.9; 8.6) 0.007

Positive anti-TPO

antibodies; % 3.9 (3.2; 4.6) 2.9 (2.4; 3.5) 0.022 1.3 (0.9; 1.9) 1.4 (1.0; 2.1) 0.677 6.7 (5.6; 8.1) 4.7 (3.7; 6.0) 0.017

TSH; mIU/L 0.69 (0.68; 0.70) 1.19 (1.18; 1.20) <0.001 0.68 (0.67; 0.69) 1.16 (1.15; 1.17) <0.001 0.71 (0.70; 0.72) 1.24 (1.23; 1.25) <0.001

Increased TSH; % 2.6 (2.1; 3.2) 2.9 (2.4; 3.6) 0.452 1.6 (1.1; 2.4) 2.4 (1.7; 3.3) 0.122 3.7 (2.9; 4.8) 3.6 (2.7; 4.8) 0.960

Decreased TSH; % 6.6 (5.8; 7.5) 6.4 (5.6; 7.3) 0.737 6.7 (5.6; 8.1) 6.4 (5.4; 7.6) 0.684 6.5 (5.4; 7.7) 6.4(5.2; 7.8) 0.940

Dichotomous data is presented as percentage and 95% confidence interval; continuous data as median and 95% confidence; all analyses are weighted by sampling weights; *p-values for differences between the studies are taken from Poisson (dichotomous data) and median regression models (continuous data)

10

4. Discussion

4.1. Iodine Nutrition in Pregnant Women and Regional Influence

The assessment of USI programme success in a population is based on the indicators of iodine

deficiency, which includes awareness in the public, iodized salt intake rate, urinary iodine

excretion levels and goiter prevalence (18) apart from more advanced parameters. The awareness

campaign on IDD and iodized salt consumption in Pakistan was poorly managed in the past

decade. It faced challenges at two fronts. First the effects of historical advertisement mistake (27)

leading to misconception about iodized salt, still exist. Second, there was a lack of locally

adoptive scientific interventions in campaigning (28). This can be clearly seen in our results

where only 13% pregnant women were aware about the IDD and iodized salt. In line with

previous studies (29,30) from Pakistan, the frequency of using iodized salt is far lower than the

international recommendations (18). Regarding UIC, in concordance with the results of a

previous study for our study region (31), the median UIC of 131 µg/L indicating a mild iodine

deficiency in pregnant women. The prevalence of goiter is in consonance with previous studies

conducted in the same region in school aged children (32,33).

In spite of huge differences in the urban and rural disparity index in Pakistan (KPK in particular)

(9), the odds for having greater knowledge about IDD, iodized salt intake, prevalence of UIC

<150mIU/L and goiter prevalence did not differ among urban and rural pregnant women.

Although due to ease availability and preference of selling in the urban areas in the big towns,

iodized salt intake in consonance with national nutrition survey 2011 (31) was higher.

Consequently goiter prevalence was lower in the urban than in the rural areas, although we could

not observe a significant difference in UIC among pregnant women from rural and urban origin.

The high goiter prevalence in district Karak is a result of low intake of iodized salt, geography

and previous history. The higher odds of rural pregnant women than the urban; to have

knowledge on IDD and having higher iodized salt intake in Lakki Marwat district may be related

to higher rural health standards and differences in rural/urban health care providers in

comparison to other districts (34). The lower goiter prevalence in this district may be because of

an already high intake of iodized salt, with the possibility of higher natural soil iodine in the

11

drinking waters and to the higher iodine contents in the sedimentary rock formation of district

Lakki Marwat (35,36).

4.2. Monitoring the Prevalence of Thyroid Disorders in North-East Germany

A general decline in IDD was observed during the last decade in the North-East German

population, in spite that an increase was observed in the self-reported diagnosed thyroid

disorders and treatments by thyroid medication. The increase in self-reported diagnosed thyroid

disorders and treatments by thyroid medication may be due to following factors apart from

increased awareness. First, due to therapeutic misjudgment prescription of thyroxine for non-

thyroid indications may not be ruled out, as observed in the Framingham (37) and DanThyr

studies (38). Second, it may be because of the wrong use of TSH reference intervals obtained

from the data in SHIP-0. Additionally, the different devices used in ultrasound for examination

of thyroid nodules in the two cohorts render non-comparable results. So, the probable increase in

prescription rate of thyroxine for the treatment of thyroid nodules in SHIP-Trend-0 may also not

be ruled out entirely.

In line with a general decline reported across Germany (39), a slight decline was observed in the

median iodine excretion levels between SHIP-0 and SHIP-Trend-0, but importantly without

detrimental effects. Median iodine excretion levels were lower in females (particularly in

younger women) than in males in both studies. A greater than normal intake of water will

increase the urine volume, leading to lower urinary creatinine and lower iodine concentrations,

but usually will not reduce the amount of creatinine excreted daily (40). Thus, the

iodine/creatinine ratio adjusts for differences in fluid intake and may provide a better estimate of

the true iodine intake in young females. On the other hand, there was a marginal but significant

increase in median thyroid volume in women, while goiter prevalence remained nearly

unchanged. In contrast thyroid volume and goiter prevalence decreased in men. This sex-

specific difference may be explained by a suboptimal iodine status in women compared to men.

When improving iodine supply there is always a risk to overcompensate, which may result in a

higher prevalence of hypothyroidism and thyroid antibodies. However, it depends on the pattern

of supplementation. A sudden, strong or periodic increase in iodine intake may provoke the

formation of thyroid antibodies and hypothyroidism, while a consistently optimal iodine intake,

12

like in our study (14,16) and in a Chinese study (15) does not. The former effect was observed in

studies from Denmark and Slovenia (41,42). Rather, we observed a decrease in the prevalence of

elevated and positive anti-TPO Abs between SHIP-0 and SHIP-Trend-0, which along with

equilibrium in prevalence of hypo- and hyperthyroidism argue for an optimal iodine supply in

our study region over the past two decades. It is evident that the current and history of iodine

supply to a region determines the distribution of TSH values of the population (24). Going

through transition in iodine supply from deficiency to sufficiency− accordingly TSH distribution

may shift from left to right if the iodine supply is persistent (21,22). We assume that the change

in TSH distribution we observed is mainly related to the improved iodine supply. A similar

association has been previously reported for the Danish population (43).

4.3. The Common Lessons

The IDD prevention programme of Germany comparatively presents a good example for

Pakistan to adopt, in order to reduce the long-term effects of iodine deficiency in the general

population. The IDD prevention programme in Germany has improved in many aspects in almost

the same time period since Pakistan adopted the USI programme (6,14). Germany has adopted a

nationwide uniform legislation for the IDD prevention (13). The IDD prevention programme is

regularly monitored by the nationwide studies in children, adolescent and adults [Studie zur

Gesundheit von Kindern und Jugendlichen in Deutschland (KIGGS) (13) and Studie zur

Gesundheit Erwachsener in Deutschland (DEGS) (12) and regional studies such as SHIP

(14,16,44). Furthermore, there is central advisory body Arbeitskreis Jodmangel, which provides

support through intensive educational work and with the help of service material for

professionals and end users in improving iodine supply and further to raise awareness of thyroid

health (45). However, Germany is lacking in studies on iodine deficiency effects on pregnant

women and neonates. Also options to control the effectiveness of IDD prevention is hampered

by limited or even not at all possible access to valid information on incident thyroid diseases,

treatments and costs in the national health-care system.

On Pakistani side, in spite of implementation problems, lots of effort on the iodized salt

production and supply have been made (46). There is a strong network present for the IDD

control at the national, provincial and district level (46). However, due to lack of proper

planning, political will, and monitoring as well as myths regarding iodized salt and

13

socioeconomics, the benefit to the end user is still impending (6). The “IDD control bill 2009” is

still awaiting approval from the national parliament, while provinces have differential adaptation

of pre-existing laws (6). The monitoring of IDD control programme is poorly managed. There is

no existence of national or regional monitoring studies and monitoring mechanism are affected

by insufficient resources; over-reliance on spot-test results; insufficient consideration of quality

assurance systems; and poorly established study protocols, laboratory resources, and expertise

(6,46). In spite of quantitative and qualitative differences in IDD prevention programme both

countries have a lot of space to work on many fronts regarding iodine deficiency elimination.

This may be in the form of utilizing expertise from Germany to assess prevalence and incidence

of common risk factors, subclinical disorders and clinical diseases related to thyroid dysfunction

and to investigate associations and interactions among them and with other disorders. From

Pakistan; due to lacking previous studies, qualitative data may be produced to look for the course

of iodine deficiency related disorders in general and targeted populations. Quality of data

collection may be optimized and standardized according to the German standards.

From future perspective both the countries need registry data for thyroid related outcomes,

regarding health care patterns, decision making, and delivery, as well as the subsequent

association of these factors with patient outcomes. There is dire need for cost effective analysis

of IDD prevention programme to adopt systematic approach for balancing resource implications

(cost) against results (effectiveness) of alternatives and is preferable to other approaches such as

gut feelings, or educated guesses. The results of cost effective analysis will provide decision

makers with information on costs, effectiveness, and the relationship between the two (i.e., the

value attained). A central advisory board with updated knowledge funded from public sources

may be established to give recommendation to the governmental authorities, general public for a

sustained programme for the elimination of IDD. Coordinated information campaigns organized

by central agencies are very important to bring awareness in public about the health benefits of

iodized salt, and health implications of iodine deficiency. The most important aspect may be to

develop a political will by enhancing the awareness among the politicians who may directly

influence the policy making infrastructure. A sustained programme is needed for the elimination

of IDD, as IDD is not a condition like smallpox, for which when once virus is removed would

not emerge again. Unless effective dietary supplementation programs are sustained, the people of

these regions will continue to suffer iodine deficiency disorders.

14

4.4. Strengths and Limitations

For the first time the iodine nutritional status with its regional effects was reported from

socioeconomically deprived districts with the largest study population of pregnant women in

Pakistan. Strengths of the SHIP data are the population based design, and that both SHIP studies

were conducted in nearly the same study regions ten years apart. In both SHIP studies

examinations were executed in the same laboratory with a common approach to high

standardization of measurements.

Our data from Pakistan was limited by not providing the personal educational level, occupation,

socioeconomic status and receiving or not receiving health and prenatal care. Further we had not

assessed iodine in salt due to resource limitations. In the SHIP studies different thyroid ultrasound

devices were used, which particularly led to a higher detection rate of thyroid nodules in SHIP-TREND-0

than in SHIP-0. In SHIP-Trend-0, we had no data on fT3 and fT4, making it impossible to distinct overt

and subclinical forms of thyroid dysfunction. Additionally, results may be affected by selection bias as

the participation reduced to 50.1%, in SHIP-Trend-0 as compared to 68.8% in the baseline cohort.

Though inverse probability weights were calculated for SHIP-Trend-0 study participation and used

multiplicatively to the base-weights to reduce selection bias. We present our results on the basis of

cross sectional data− of which we cannot draw causal inference.

5. Conclusion

In pregnant women in Pakistan due to insufficient awareness campaigns and low literacy ratio in

rural areas urinary iodine excretion levels indicate a stable iodine supply, which is still not

sufficient. Our results show that rural/urban disparity is affecting the IDD prevention program in

rural districts, but not in general. The SHIP data indicate that the improved iodine supply over

the past two decades in Germany is paralleled by a reduction in prevalence of IDDs, while no

increase was observed in markers of autoimmune thyroid disorders arguing for an optimal iodine

supply of the general adult population in Northeast Germany. The increase in prevalence of

diagnosed thyroid disorders and the intake of thyroid medication might be because of

inappropriate therapeutical decisions which should be made with caution, based on regional TSH

reference ranges, its prognostic value, and compliance with treatment.

15

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7. Scientific work

Article in Final Editor Review of “Thyroid”

7.1. Regional Influence on Iodine Nutritional Status of Pakistani Pregnant Women

Rehman Mehmood Khattak1, 6, Zuhra Saifullah2, Ghulam Khadija3, Amina Fayyaz3, Salma

Zaman4, Mahwish Gul4, Muhammad Nasir Khan Khattak5, 7, Birgit Schauer1, Henry Völzke1,

Till Ittermann1,

1Institute for Community Medicine, University Medicine Greifswald, Germany,

2Department of Zoology, University of Peshawar, Pakistan,

3Department of Zoology, Kohat University of Science and Technology (KUST), Kohat, Pakistan,

4Department of Animal Sciences, Quaid-i-Azam University Islamabad, Pakistan,

5Department of Zoology, University of Hazara, Mansehra, Pakistan,

6Department of Zoology, Islamia College Peshawar (CU), Pakistan,

7Department of Applied Biology, University of Sharjah, Sharjah, United Arab Emirates

Short running title: Iodine Nutritional Status in Pregnancy in Pakistan

Keywords: Iodine Deficiency Disorder, Pregnancy, Goiter Prevalence, Iodized Salt, Pakistan

21

Regional Influence on Iodine Nutritional Status of Pakistani Pregnant Women

Rehman Mehmood Khattak1, 6, Zuhra Saifullah2, Ghulam Khadija3, Amina Fayyaz3, Salma

Zaman4, Mahwish Gul4, Muhammad Nasir Khan Khattak5, 7, Birgit Schauer1, Henry Völzke1,

Till Ittermann1

1Institute for Community Medicine, University Medicine Greifswald, Germany, 2Department of

Zoology, University of Peshawar, 3Department of Zoology, Kohat University of Science and

Technology (KUST), Kohat, Pakistan, 4Department of Animal Sciences, Quaid-i-Azam

University Islamabad, 5Department of Zoology, University of Hazara, Mansehra, Pakistan,

6Department of Zoology, Islamia College Peshawar (CU), Pakistan, 7 Department of Applied

Biology, University of Sharjah, Sharjah, United Arab Emirates .


Keywords: Iodine Deficiency Disorder, Pregnancy, Goiter Prevalence, Iodized Salt, Pakistan

22

Abstract

Background

Keeping the rural-urban disparities in Pakistan in mind, this study aimed at assessing the regional

influence on nutritional iodine status of pregnant women, the most vulnerable group for iodine

deficiency.

Methods

Data were collected from 1246 pregnant women in all trimesters of pregnancy who visited pre-

natal clinics for routine checkups in five districts of the Khyber Pakhtunkhwa province.

Information on iodized salt intake and knowledge on iodine deficiency disorders (IDD) were

obtained through an interview questionnaire. Goiter and urinary iodine excretion levels were

assessed by the palpation method and the Sandell-Kolthoff reaction, respectively. Logistic

regression analysis was used for quantifying an association of residence (rural/urban), trimester

of pregnancy and previous abortion on the outcomes; knowledge about IDD, iodized salt intake,

presence of goiter and urinary iodine concentration (UIC) <150 μg/L.

Results

Overall, 87.7% of pregnant women had no knowledge about IDD, while only 21.0% were taking

iodized salt. Goiter prevalence in pregnant women was 25.5% and an UIC >150 μg/L was

observed in 41.3%. There were no significant differences between pregnant women from rural

and urban settings in regions with a solid socioeconomic status with respect to knowledge on

IDD, iodized salt intake, iodine deficiency and prevalence of goiter. Urban/rural differences were

observed only in socioeconomically deprived districts. Only in the district Lakki Marwat,

pregnant women from urban regions had higher odds of having knowledge on IDD and iodized

salt intake than those from rural regions. Trimesters of pregnancy and previous abortions of

pregnant women had no significant effect on the outcome measures.

Conclusions

UIC levels indicate a stable (in comparison to the national nutrition survey from 2011) but

mildly deficient iodine supply, while goiter prevalence and lack of iodized salt intake remain

23

high, especially in rural areas. Rural/urban disparities were observed only in socioeconomically

deprived districts, which limit the effectiveness of the IDD prevention program in rural areas in

Pakistan. The results suggest that the implementation of mandatory salt iodization needs to be

improved and the program’s effectiveness monitored to protect pregnant women from the

adverse health effects of sub-optimal nutritional iodine status.

24

Introduction

Pakistan is a country with endemic iodine deficiency resulting in high goiter prevalence (1, 2). A

program for the control of iodine deficiency disorders (IDD) has been adopted since 1994.

Although the iodization of salt is mandatory in the country according to the partially

implemented, drafted “IDD control bill 2009” (3), but its implementation is not regulated and

there is no regular monitoring of the program’s effectiveness (1). For these reasons, 20-50% of

all school-aged children suffer from goiter in certain areas (4-6). The Khyber Pakhtunkhwa

(KPK) province located in the Northwest is the most endemic IDD region in Pakistan, where the

prevalence of goiter is not consistent with the reported household usage of iodized salt (1).

Iodine deficiency in women of reproductive age is a big issue in Pakistan. The results of

the national nutrition survey in 2011 revealed that 48% of all 1460 women of reproductive age

(15-49 years) had less than the recommended urinary iodine concentration (UIC) of 100 µg/L,

while in the KPK province this prevalence was even lower (23.9%) (7). The median UIC of

women of reproductive age was 104 μg/L, whereas the median reported from KPK was 148.6

μg/L. In a recent study in pregnant women (n=202) (4) from the Charsadda district located in the

Peshawar valley the overall goiter prevalence was 20.7%, while median UIC was only 89.5

µg/L, which is far below the WHO recommended level of 150 µg/L (8). It is a common issue of

IDD surveys in Pakistan, that remote and rural districts are not covered resulting in biased

estimates about the progress in the correction of IDD (1). Our study includes data from two

districts located in the Peshawar valley (Peshawar and Nowshehra) (9) and three other districts

(Kohat, Karak and Lakki Marwat) not being part of the Peshawar valley. These five districts

represent a good cross section in terms of urbanization, topography, socioeconomics and

potential environmental threats to natural soil iodine including floods, drought, intense rainfall,

earthquake and cyclones (7, 9-12). The previous study performed in Charsadda did not focus on

regional effects on the nutritional iodine status of pregnant women. In the previous study the

study population (202) was very small, while in our study 1246 pregnant women were included.

In comparison to the previous study, we enrolled more parameters to improve the understanding

of potential causes underlying iodine deficiency.

During pregnancy, iodine supplementation is very important because more iodine is

required due to an increased renal clearance of iodide in early gestation, which persists until birth

25

of the child (13, 14). It is recommended that iodine intake should be optimized before or early in

pregnancy to prevent fetal damage. An optimal iodine intake is not only needed for maintaining

maternal euthyroidism, but is also needed for fetal thyroid hormone production and brain

development (8, 13). The WHO, the Iodine Global Network (IGN), and UNICEF, agreed on a

recommended daily allowance of 250 µg/day for pregnant women compared to 150 µg/day for

non-pregnant women (8). A median UIC of 150-249 µg/L is recommended by WHO as an

indicator of adequate iodine intake in pregnant women. In countries or regions where 90% of

households are using iodized salt and the median UIC in school-age children is around 100 µg/L,

WHO recommends iodine supplementation in pregnancy and infancy (8).

The Pakistani society is exposed to disparities between genders, regions, societal,

socioeconomic, and educational factors, which can affect health outcomes. Apart from

differences in living standards, these disparities also trigger migration from rural to urban areas

(15). A recent survey reported significantly higher disparities between rural and urban areas for

both genders, education, livelihood, health services, and sanitation in KPK (16). The observed

sex disparity highlights social and economic dominancy of men in families located in rural

regions, whereas individuals from urban regions had better education and education facilitation

related to infrastructure and quality (particularly at grade 10 and above). Furthermore, the quality

of infrastructure, housing, health services, drinking water supply, transportation, communication

and sanitation were also better in urban areas compared to rural regions.

The purpose of this study was to evaluate the nutritional iodine status of pregnant women

and associated factors with particular emphasis on differences between rural and urban residents

who live in a province with endemic iodine deficiency.

Materials and Methods

Study Area

This study was conducted in five districts of the KPK province in northwestern Pakistan (Figure

1). A choropleth map of the study region was created using ArcGIS for Desktop 10.3.1.

26

Study Design and Subjects

This cross-sectional study was conducted in randomly selected (public and private) prenatal

clinics in the selected districts. If private clinics declined to participate, the data collection was

restricted to public clinics only. The details of the data collection with name of the clinic, its

official status and number of participants is given in supplementary table 1. The details of the

public health care delivery units were obtained from the office of district health officers. In KPK,

maternal care is provided by three tiers of the public health delivery system: the primary health

care units (basic health units, rural health centers), the secondary care hospitals [district and

tehsil (administrative sub-division of the district) headquarter hospitals], and the tertiary

care/teaching hospitals and mother and child care centers (11).

Data were collected from pregnant women, who visited prenatal clinics for their routine

checkup between March and September 2012. From every district, data were collected from a

subtotal of almost 250 pregnant women reaching to a total of 1260 including participants from

all five districts. Pregnant women with self-reported chronic medical disorders such as

hypertension, diabetes mellitus, tumors, renal diseases, with regular use of any medication and

with history of blood borne diseases were not included in the study. The proportion of pregnant

women who declined to participate was not recorded. After exclusion of 14 individuals with

insufficient amount of urine for UIC analysis, the final study population consisted of 1246

pregnant women.

The gestational age was determined by the gynecologists in antenatal clinics based on the

last menstrual period. Gestational age was calculated from the first day of the last menstrual

period with gestational ages of ≤14.9, 14.9 to 28.9, and ≥29 weeks comprising the first, second,

and third trimesters of pregnancy, respectively. Information on the number of previous

pregnancies and/or abortions (fetal loss due to various reasons, not including voluntary

termination of pregnancy) was obtained. A written informed consent was obtained from each

participant before data collection. An institutional academic research committee approval of

Kohat University of Science and Technology (KUST), Kohat, Pakistan was obtained for this

study.

27

Iodized Salt Intake and Knowledge

All participants were asked to complete a short interview questionnaire containing questions

related to iodized salt intake. The questionnaire comprised questions related to knowledge on

iodized salt consumption and on health implications associated with inadequate intake of iodized

salt. It further included questions regarding knowledge about IDDs, sources for the input of

knowledge about IDD including media, doctors, or schools. In Pakistan the universal salt

iodization (USI) program has been affected by lack, uniformity of awareness and misconceptions

about IDDs and iodized salt (1). Thus, knowledge about IDD and iodized salt affects the

utilization of iodized salt, UIC levels, and goiter prevalence. Questions related to nutritional

practices focused on intake of iodized salt, identification of sources of iodized salt, and reasons

for or against utilization of iodized salt.

Urinary Iodine Concentration

The participants were asked to give a urine sample in the vicinity of the antenatal care unit. A

total of 1246 urine samples (≈ 2 ml) were collected in tight screw-capped plastic bottles. Each

bottle was labeled with a sample number, name of the district, name of the antenatal care unit,

and time and date of urine collection. The urine samples were kept in a cool dry box and

transported to the Institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar, where

the samples were chilled at 4ºC until urinary iodine analysis. UIC was measured using a

modification of the Sandell-Kolthoff reaction with spectrophotometric detection. The inter-assay

coefficient of variation (CV) was calculated to be 5.6%. Evaluation of iodine status was based on

median UIC categories defined by the WHO/IGN (8). These are: recommended – median 150-

249 μg/L; mild iodine deficiency – median <150 μg/L.

Goiter Assessment

For goiter assessment the WHO/UNICEF/IGN recommended palpation method was used. All the

pregnant women were examined for the presence of palpable goiter as follows. No palpable and

visible goiter was graded as 0. Palpable but no visible goiter was graded as I, and palpable and

visible goiter as Grade II. Palpation examination was carried out by trained examiners in all the

districts, who were trained in the central laboratory of Kohat University of Science and

28

Technology (KUST), Kohat, Pakistan. The severity of the goiter prevalence in the whole study

area and the concerned district was outlined based on the recommended WHO/IGN criteria (8).

Statistical Analysis

Categorical data are presented as absolute numbers and percentages, while continuous data are

presented as absolute numbers and mean or median. Analyses were carried out to identify

differences in iodine deficiency between the urban/rural distribution, trimesters, and previous

abortions among pregnant women of each district. Multivariable logistic regression analysis

adjusting for age was used to regress the outcome measures (knowledge about IDD, iodized salt

intake, UIC <150 µg/L and goiter prevalence) on regional influences (as exposure) in each

specific district. These results are presented as odd ratios and their 95% confidence intervals. A

p-value of <0.05 was considered statistically significant. All analyses were carried out with Stata

11.2 (Stata Corporation, College Station, TX, USA)

Results

The description and location of the studied districts (7, 10-12, 17) is given in Table 1 and Figure

1. The mean age of pregnant women was 27.1 years (age range: 15-50 years) (Table 2). The

baseline characteristics and numbers of studied pregnant women in all the districts are

summarized in tables 2 and 3.

Knowledge about IDD

The majority of pregnant women (88.0%) had no knowledge about IDD (Table 3). Interestingly,

13.5% of pregnant women were utilizing iodized salt despite of the fact that they had no

knowledge about IDD. The major sources of awareness about IDD for the pregnant women were

printed or electronic media (37.3%), schools (19.0%), and doctors (16.3%) (Supplementary table

2). While explaining the reason for taking iodized salt, 50.8% pregnant women reported that they

were taking it for better health, while 20.6% were taking iodized salt because of its better taste

and 13.7% because of family preferences (Supplementary table 3). When asked about the

definition of better health, 46.6% of pregnant women replied that it inhibits goiter development

29

and 12.0% reported it prevents IDD in general. However, 24.8% of the pregnant women taking

iodized salt for better health could not define better health. Among the 79% of the pregnant

women not taking iodized salt, most of them (44.5%) could not state any reasons for not taking

iodized salt, while 36.6% reported that it negatively affects reproduction, and for 17.0% iodized

salt was too expensive (Supplementary table 3).

The results based on logistic regression analysis show that; except for Lakki Marwat

district, the odds of having knowledge about IDD did not differ between rural and urban

pregnant women (Figure 2). In Lakki Marwat district, the pregnant women from urban residence

had higher odds of having knowledge on IDD than their rural counterparts.

Iodized Salt Intake

Around 79.0% pregnant women were not taking iodized salt (Table 3). Iodized salt intake in

pregnant women was higher in the big cities (Peshawar, Nowshehra) than in the smaller ones.

The highest intake was reported from Peshawar district (45.2%) and the lowest intake of iodized

salt was observed in Karak district (3.6%). In comparison to Peshawar iodized salt intake was

significantly lower in pregnant women in all other districts.

Frequencies of iodized salt intake were not significantly different between the first and

the other trimesters of pregnancy (Table 3). Similarly, iodized salt intake of pregnant women did

not differ significantly if they had a history of a previous abortion.

Iodized salt intake was higher in urban than in rural pregnant women, but this difference

was except for the Lakki Marwat district not statistically significant (Figure 2).

Urinary Iodine Concentration

In 41.3% of the pregnant women, we observed a UIC of >150 µg/L (Table 3). The median UIC

level for the pregnant women was 131 µg/L. The prevalence of UIC <150 µg /L was

significantly higher among pregnant women in the Nowshehra, Karak and Kohat districts in

comparison to Peshawar. The prevalence of UIC <150 µg/L in pregnant women did not differ in

rural and urban areas (Table 3). Similarly, the odds of having UIC <150 µg/L was not different

between rural and urban areas in all the districts (Figure 2). However, in Nowshehra district it

barely missed statistical significance. Knowledge about IDD was a contributory factor in

30

overcoming iodine deficiency. Pregnant women who had knowledge about IDD had a

significantly lower prevalence of UIC <150 µg/L (Table 3). The frequency of UIC <150 µg/L

was not significantly different among the pregnant women in all the three trimesters of

pregnancy. Previous abortion of pregnant women was not a determining factor for iodine

deficiency.

Goiter Prevalence

The goiter prevalence in pregnant women was 25.5%. Goiter prevalence was lowest in the Lakki

Marwat and Peshawar district (Table 3). A goiter prevalence of 44.1% was measured in the

Karak district, which was significantly higher than in Peshawar district (19.6%). There was no

significant difference in goiter prevalence of rural compared to urban pregnant women (Table 3).

Consistent with these findings, the odds of having a goiter were not different between women

from urban and rural areas (Figure 2).

Discussion

The present study was conducted to evaluate the rural/urban differences in nutritional iodine

status among pregnant women in the KPK province of Pakistan. Overall, there was mild iodine

deficiency among pregnant women. In a country with a history of iodine deficiency, urban

residence and awareness about IDD were associated with iodine sufficiency among pregnant

women.

Effective public health mass media campaigns are dependent on the literacy ratio of the

community, the medium of marketing and the quality of the message (18). In Pakistan, the

awareness campaign on IDD and iodized salt consumption has been poorly managed in the past

decade. This is evident from the results presented here that show a low level (12%) of awareness

about IDD or iodized salt utilization of pregnant women (13.5%) without knowledge about IDD.

This may partially be explained by a dissemination of information between the governmental

authorities and the general population for the historical advertisement mistake− in which iodine

intake advertisement was immediately followed by a fertility control advertisement on national

television− in a culturally conservative and religiously intact society. It resulted in misconception

31

of “iodized salt negatively affecting fertility”, which is still frequently believed in Pakistan (20).

Additionally, this may also be explained by the lack of locally adoptive scientific or social

interventions in campaigning (20, 21), involving local community through the Jirga system or

through the clerics. Jirga is an informal gathering of men that has a key governing and decision-

making role in the Pushtun community of KPK. A recent study conducted in a culturally and

socioeconomically similar population like ours showed a lower prevalence of goiter and higher

prevalence of iodized salt intake after intervention against IDD (20). Similarly, polio eradication

campaign, facing similar misconceptions like iodized salt, is progressing towards a probable end

in Pakistan (among the three countries around the world to have existence of polio virus), after

involving the local clerics for convincing the general public through direct speeches and fatwas

(22, 23).

Despite of limited access to electricity, particularly in rural areas of Pakistan, the

strongest medium promoting awareness about IDD are printed or electronic media. Our results

highlight the importance of media in awareness campaigns, which is consistent with other studies

(24, 25). However, we did not collect information about− when for the first time the pregnant

women started knowing about iodized salt or IDD. So, it is not certain whether knowing about

IDD represents the current or their previous knowledge from a decade ago, given the schooling

age as the second highest source of knowledge for all pregnant women. This is in line with the

phases of governmental efforts regarding awareness about iodized salt and IDD (1).

Urbanized settings are more suitable for awareness campaigns due to comparatively

higher chances of high-quality education and social integration. There are huge differences in

urban and rural disparity indices in Pakistan (KPK in particular) (16). Regarding iodine, iodized

salt and IDD the previous studies have reported a higher knowledge in urban than in the rural

populations (26-28). In contrast, we observed no difference in odds, between urban and rural

pregnant women for having greater knowledge about IDD. We suppose that due to focus of the

government on polio eradication during the last decade, the vigorous campaigning (including

awareness in population) for the IDD control program was slow. Further, because of missing

iodine supplementation in women during pregnancy, pregnant women in rural and urban areas

have similar knowledge about iodized salt or IDD. The Lakki Marwat district, in which rural

pregnant women had higher odds of having knowledge about IDD, was an exception. This may

32

be related to differences in rural/urban health care providers in comparison to other districts (11).

Thus, the literacy ratio and poverty index alone could not explain these differences.

Iodized salt intake is indispensable in populations less relying on foods rich in iodine (8).

The rapid physiological changes during pregnancy and the higher iodide requirements in

pregnant women define them as a special target group for iodine supplementation (13). Our

results show that a high frequency (79%) of pregnant Pakistani women were not taking iodized

salt (29). A low intake of iodized salt was reported in previous studies from the urban

metropolitan city of Lahore (34%) in 2009 (30) and a study from Faisalabad (6%) in 2000 (31)

from Punjab province. Likewise, the national nutrition survey in 2011 reported an intake of

iodized salt in only 40% of all women of reproductive age (7). Apart from the myth associated to

the iodized salt, the price of iodized salt is three times higher in comparison to the non-iodized

salt. Moreover, the price for iodized salt has been doubled during the last decade. These factors

contribute to a general less frequent use of iodized salt (1). In addition, disparities in salt intake

prevalence across Pakistani studies may be explained by regional differences and changes over

time (1). As demonstrated in our study, the prevalence of iodized salt intake is significantly

different even between districts of one province. This finding clearly demonstrates the need for a

consistent iodine fortification program throughout Pakistan. Overall, our and all previous studies

indicate that the prevalence of pregnant women taking iodized salt is far lower than international

recommendations (8).

Iodized salt intake was higher in the big cities like Peshawar and Nowshehra than in the

smaller ones (Karak and Kohat). Iodized salt intake was also higher in the pregnant women of

urban areas compared to rural areas. These results are consistent with data from the national

nutrition survey in 2011 (7). This may be due to preference of selling the iodized salt, because of

their organized packing in the urban areas of the big towns, apart from awareness. This is

highlighted by no significant differences in the pregnant women’s odds of iodized salt intake

from urban and rural residence. A recent study in the rural suburb of district Peshawar revealed

that− against the household iodized salt consumption of only 2.6% with awareness in general

public only 3%− 67.9% of the shopkeepers in the area regularly stocked iodized salt before

intervention (20). These results clearly show that iodized salt use is affected by its availability in

urban population, apart from other reasons. However, this is not a generalized rule, particularly

33

in the smaller towns. Increased urbanization may also increase the prevalence of iodized salt

intake. A good example can be elaborated from the district Karak in our results, where there was

extremely low intake of iodized salt among pregnant women in the whole district. However, due

to the urbanization effect reinforced by the higher literacy ratio of urban women− resulted in

marginal odds to have knowledge about IDD− the prevalence for iodized salt intake was high in

the urban settings, although around 93% of the population in this district lives under rural

conditions. District Lakki Marwat was the only exception where there was a reversed trend;

possibly because of higher rural health standards and significant advantage of the rural pregnant

women to have knowledge about IDD than in other districts may have contributed to the high

iodized salt intake in rural pregnant women.

UIC is a well-accepted sensitive marker and at population level a useful measure to

assess changes in the iodine status. The median UIC was lower (131 µg/L) than recommended

by the WHO, indicating a mild iodine deficiency. This finding is in concordance with those

reported in the national nutrition survey-2011; 149 µg/L for women of reproductive age in the

whole KPK province (7). However, UIC in our study is higher than in a study conducted in

school aged children of the same study region in 2015-16 (5, 6). Frequency of having UIC <150

µg/L were significantly higher among pregnant women in the districts Nowshehra, Karak and

Kohat in comparison to Peshawar. This is explained by their iodized salt intake and goiter

prevalence in line with previous history of iodine deficiency (1). We could not observe a

significant difference in UIC among pregnant women from rural and urban origin except a

marginally significant result in district Nowshehra. This finding is in in contrast to the results of

national nutrition survey-2011, where prevalence of normal and median UIC was higher in rural

areas than in urban.

In accordance with other studies in regions with low daily dietary iodine intake UIC

levels remained nearly stable or increased with trimesters of pregnancy (14, 32, 33). The increase

in iodine loss can be accounted for renal iodine loss during pregnancy, reflecting not only daily

dietary iodine intake but also initial thyroid iodine content depletion in the absence of increased

dietary iodine intake (14). There is an established association between the iodine deficiency and

reproductive failures including abortions (34, 35). The risk of reproductive failure is twice as

high in iodine deficient women than in woman with normal iodine level (34). This influence of

34

iodine deficiency is also demonstrated by the reduction in reproductive failures when iodine is

administered to women before pregnancy (36, 37). However, according to our results, previous

abortion could not motivate the pregnant women to overcome iodine deficiency, which is

possibly due to lack of awareness, resources or access. Hence the loss of iodine in the course of

successive pregnancies, iodine loss in trimesters of pregnancies (14) may further aggravate the

iodine deficiency related reproductive complications.

Pregnancy-induced goitrogenesis is evident from the association of biochemical features

of thyroidal stimulation with volumetric changes in the gland at least in conditions with a low

iodine intake (32) and this increase is observed accordingly during the trimesters of pregnancy

(13). There is no previous study reporting goiter prevalence in pregnant women in our study

region, but our results are in consonance with the previous studies conducted in the same regions

in school aged children (4-6). It is also known that goiter formation during pregnancy can be

prevented by increasing the iodine supply during pregnancy (33), compensating the increased

renal loss of iodine contributed to thyroid enlargement. Our study region had been passing

through a transition phase from being historically iodine deficient towards betterment. Naturally,

in the transition phase we may still expect goiter prevalence in our population. Additionally, the

environmental factors affecting natural soil iodine may also be contributing at population level

(1). It has been reported that thyroid volume in pregnant women increases significantly

compared to the non-pregnant women and accordingly during the trimesters of pregnancy (13),

but our results show a non-significant decrease and then increase in goiter prevalence in second

and third trimester of pregnancy respectively (Table 3). However, it may be argued that, due to

low sensitivity of goiter determination through palpation rather than ultrasound and further due

to interobserver variabilities, the precise estimate of goiter prevalence may have been

confounded by these factors. Goiter prevalence was lower in the urban than in the rural areas.

Reciprocated by the lower intake of iodized salt, geography and previous history (38), goiter

prevalence was almost twice higher in the Karak district than in the other districts. The factors

for the lowest goiter prevalence from district Lakki Marwat may be an already higher intake of

iodized salt, with the possibility of higher natural soil iodine in the drinking waters and to the

higher iodine contents in the sedimentary rock formation of district Lakki Marwat (12, 39). This

may be the reason that there are no previous reports of goiter prevalence and iodine deficiency

for any group from this region in history.

35

The strength of our study is that it is the first study from socioeconomically deprived

districts with the largest study population of pregnant women in Pakistan ever been studied. Our

study is limited by not presenting the personal educational level but we have interpreted results

based on the literacy ratio of the district concerned. Similarly we had not collected data about the

occupation, socioeconomic status and further about pregnant women receiving or not receiving

health and prenatal care. Additionally selection bias may have occurred as this study targeted

pregnant woman attending prenatal clinics. The data reporting from pre-natal clinics was self-

limiting by the fact that only 50% (11), women receive care from any level of prenatal care in

KPK province of Pakistan. Hence, results from this study cannot be generalized to the entire

population of the study region. A bias in the results may have been introduced because data from

private clinics was not available from all the districts due to non-response and cultural factors.

However, the results provide a very useful reference for woman attending prenatal clinics for this

province given the large sample size. Further, we had not assessed iodine in salt due to resource

limitations. Goiter prevalence may be confounded by interobserver variability and low sensitivity

of goiter determination by palpation rather than the ultrasound.

Conclusion

Urinary iodine excretion levels indicate a stable iodine supply, but still not sufficient based on

the goiter prevalence and iodized salt intake rate. This may be due to insufficient awareness

campaigns and low literacy ratio in rural areas. Our results show that rural/urban disparity is

affecting the IDD prevention program in rural districts, but not in general, and there is urgent

need for a uniform approach throughout Pakistan towards the elimination of iodine deficiency.

36

Acknowledgments

This project has received funding from the European Union’s Horizon 2020 research and

innovation program under grant agreement No. 634453. We also received partial support for the

analyses from the German Research Foundation under the project number DFG-VO955/10-2.

We acknowledge the contribution of all the persons; hospital administration, physicians,

provincial and district level health department administration and Department of Zoology; Kohat

University of Science and Technology (KUST), Kohat, Pakistan for their support in data

collection.

Author Disclosure Statement

No competing financial interest exist

Address for correspondence:

Rehman Mehmood Khattak

Institute for Community Medicine,

University Medicine Greifswald,

Walther Rathenau Str. 48, 17475 Greifswald, Germany

Phone: +49 - 3834 - 866683

FAX: +49 - 3834 – 867541

e-mail: [email protected]

mailto:[email protected]

37

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41

Table 1. Characteristics of the Study Area with Potential Threats to Natural Soil Iodine

Characteristics Lakki Marwat Karak Kohat Nowshehra Peshawar

Total Urbanized area

(%) 9.7 6.5 27.0 26.0 49.0

Estimated population

(in million) 0.065 0.058 0.076 0.124 0.283

Literacy ratio

(total/female) (%) 54/29 58/36 47/28 50/35 56/36

Literacy ratio female

(Urban/rural) (%) 49/26 62/34 49/23 41/32 45/26

Topography Desert with

mountainous

outskirts

High mountain

ranges with barren

plain areas

High mountain

ranges with fertile

plain areas

Plain riverine with

mountainous

outskirts

Plain, fertile,

riverine area

Potential

environmental threats

Cyclones, drought Floods, drought,

intense rainfall,

earthquake

Intense rainfall,

earthquake

Floods, intense

rainfall

Floods, intense

rainfall, earthquakes

(7, 9-11) Population data is based on the 1998 census

42

Table 2. Selected Baseline Characteristics of Pregnant Women in Five Districts

Characteristic Lakki

Marwat Karak Kohat Nowshehra Peshawar

Age (years) 26.3 ± 5.5 28.2 ± 4.9 28.5 ± 4.3 25.5 ± 5.9 27.0 ± 6.2

Age range

(years) 15-45 17-40 17-39 15-45 16-50

BMI (Kg/m2) 26.5 ± 6.3 25.2 ± 3.6 21.3 ± 3.9 26.7 ± 5.6 26.8 ± 6.0

Locality

Rural n (%) 173 (22.1) 195 (24.9) 192 (24.5) 123 (15.7) 100 (12.8)

Urban n (%) 71 (15.3) 57 (12.3) 57 (12.3) 128 (27.7) 150 (32.4)

Trimester of

pregnancy

First n (%) 42 (17.3) 39 (16.1) 76 (31.3) 56 (23.1) 30 (12.1)

Second n (%) 94 (24.7) 53 (13.9) 99 (26.1) 73 (19.2) 61 (16.1)

Third n (%) 108 (17.3) 160 (25.7) 74 (11.9) 122 (19.6) 159 (25.5)

Previous abortion

No n (%) 210 (21.7) 181 (18.7) 194 (20.1) 194 (20.1) 187 (19.4)

Yes n (%) 34 (12.1) 71 (25.4) 55 (19.6) 57 (20.4) 63 (22.5)

Number of

abortions

0 n (%) 210 (21.7) 181 (18.7) 194 (20.1) 194 (20.1) 187 (19.4)

1 n (%) 19 ( 12.1) 39 (24.8) 27 (17.2) 31 (19.8) 41 (26.1)

2 n (%) 9 (11.8) 20 (26.3) 19 (25.0) 14 (18.4) 14 (18.4)

3 n (%) 5 (20.0) 7 (28.0) 5 (20.0) 7 (28.0) 1 (04.0)

4 n (%) 0 (0.00) 4 (40.0) 2 (20.0) 2 (20.0) 2 (20.0)

5 n (%) 1 (10.0) 0 (0.00) 2 (20.0) 2 (20.0) 5 (50.0)

6 n (%) 0 (0.00) 0 (0.00) 0 (0.00) 1 (100.0) 0 (0.00)

10 n (%) 0 (0.00) 1 (100.0) 0 (0.00) 0 (0.00) 0 (0.00)

Data presented as absolute numbers (percentages) or mean ± standard deviation

43

Table 3. Association of Iodized Salt Intake, Goiter Prevalence and Recommended Baseline UIC with Different Demographic

Characteristics

Characteristic

Survey sample

(n=1246)

Iodized salt intake

(n=262; 21.0%)

Goiter prevalence

(n=318; 25.5%)

UIC <150 µg/L

(n=731; 58.7%)

n % n (%) P value n (%) P value n (%) P value

District

Lakki Marwat 244 19.6 45 18.4 <0.001 44 18.0 0.656 57 23.4 0.096

Karak 252 20.2 9 3.6 <0.001 111 44.1 <0.000 208 82.5 <0.001

Kohat 249 20.0 27 10.8 <0.001 54 21.7 0.565 165 66.3 <0.001

Nowshehra 251 20.1 68 27.1 <0.001 60 23.9 0.244 226 90.0 <0.001

Peshawar 250 20.1 113 45.2 Ref 49 19.6 Ref 75 30.0 Ref

Residence

Rural 783 62.8 137 17.5 <0.001

209 26.7 0.218

467 59.6 0.364

Urban 463 37.2 125 27.0 109 23.5 264 57.0

Knowledge

about IDD

No 1093 87.7 147 13.5 <0.001

290 26.5 0.030

659 60.3 0.002

Yes 153 12.3 115 75.2 28 18.3 72 47.1

Trimester of

pregnancy

First 245 19.7 46 18.9 Ref 62 25.5 Ref 150 61.7 Ref

Second 379 30.4 81 21.3 0.471 85 22.4 0.367 226 59.5 0.575

Third 622 44.0 135 21.7 0.373 171 27.5 0.564 355 57.0 0.203

Previous

abortion

No 966 77.5 200 20.7 0.603

236 24.4 0.101

563 58.3 0.607

Yes 280 22.5 62 22.1 82 29.3 168 60.0

P-value calculated from logistic regression, adjusted for age, (Ref = reference category); The percentages presented are row

percentages

44

45

46

7.2. Monitoring the Prevalence of Thyroid Disorders in the Adult Population of Northeast

Germany

Rehman Mehmood Khattak*1, 4, Till Ittermann*1, Matthias Nauck2, Harald Below3, Henry Völzke1

* equally contributed as first authors

1Institute for Community Medicine,

2Institute of Clinical Chemistry and Laboratory Medicine,

3Institute of Hygiene and Environmental Medicine,

Ernst Moritz Arndt University Greifswald, Germany,

4Department of Zoology, Islamia College Peshawar (CU), Pakistan

Short running title: Monitoring of Thyroid Disorders

Keywords: Thyroid Disorders, Epidemiology, Monitoring, Prevalence Trend

47

48

49

50

51

52

53

54

55

56

57

58

7.3. Factor Affecting Sustainable Iodine Deficiency Elimination in Pakistan: A Global

Perspective

Rehman Mehmood Khattak1, 3, Muhammad Nasir Khan Khattak2, 4, Till Ittermann1, Henry

Völzke1

1Institute for Community Medicine, University Medicine Greifswald, Germany,

2Department of Zoology, University of Hazara, Mansehra, Pakistan,

3Department of Zoology, Islamia College Peshawar (CU), Pakistan,

4Department of Applied Biology, University of Sharjah, Sharjah, United Arab Emirates


Keywords: Iodine Deficiency Disorder, Goiter Prevalence, Iodine Nutritional Status Salt,

Iodization, Pakistan

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8. Appendix

A. Statutory Declaration

Hiermit erkläre ich, dass ich die vorliegende Dissertation selbstständig verfasst und keine

anderen als die angegebenen Hilfsmittel verwendet habe.

Die Dissertation ist bisher keiner anderen Fakultät vorgelegt worden

Ich erkläre, dass ich kein Promotionsverfahren erfolglos beendet habe und dass eine

Anerkennung eines bereits erworbenen Doktorgrades nicht vorliegt

Greifswald, Date: Rehman Mehmood Khattak

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B. Own Contributions

Explanation of Individual Shares in Joint Work

Data for this research was derived from pregnant women in the Khyber Pakhtunkhwa (KPK)

Province of Pakistan and from the SHIP database of the Community Medicine research Network.

The author was involved in the data collection from pregnant women in KPK, Pakistan,

The author performed the literature search, conceptual design of data analysis, explored the

theoretical framework, performed the statistical analysis and drafted all the research articles and

the thesis to their final version.

Rehman Mehmood Khattak Prof. Dr. Henry Völzke

The above information is confirmed:

Prof. Dr. Henry Völzke

Greifswald, Date:

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C. Curriculum Vitae

Personal Data

Name Rehman Mehmood Khattak

Date of Birth 07 January 1979

City of Birth Karak, Pakistan

Address

Permanent Village Askari Alikhel, Tehsil and District Karak,

Khyber Pakhtunkhwa, Pakistan

Temporary Makarenko Street 51-B, 17491, Greifswald,

Germany

Marital status Married

Education

2005-2007 MPhil. Reproductive Physiology; Department of

Zoology, Bahauddin Zakariya University, Multan,

Punjab, Pakistan

2001-2003 MSc. Zoology; Department of Zoology, Bahauddin

Zakariya University, Multan, Punjab, Pakistan

1998-2000 BSc. Biology; Government College Dera Ghazi

Khan, Bahauddin Zakariya University, Multan,

Punjab, Pakistan

Professional Occupation

2007-2014 Lecturer in Zoology (Permanent); Kohat University

of Science and Technology (KUST), Kohat,

Pakistan

2005-2007 Lecturer in Zoology (Temporary); Kohat University

of Science and Technology (KUST), Kohat,

Pakistan

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D. Scientific Output

Original articles

1. Khattak RM, Kasi KK, Schauer B, Kasi MD, Völzke H, Ittermann T. Epidemiology of

Crimean Congo Hemorrhagic Fever (CCHF) Across the Durand Line. 2018.

2. Khattak RM, Saira S, Schauer B, Khattak MNK, Völzke H, Ittermann T. Prevalence of

Underweight, Overweight and Obesity Among School Going Cchildren (6-12 Years)

From Pakistan and Disparity of Results Based on IOTF and CDC Cut-offs. 2017.

3. Khattak RM, Kühn J-P, Lerch MM, Ittermann T, Völzke H. Association of Thyroid

Function with Fat and Iron Contents of the Liver derived from MRI. 2017.

4. Khattak RM, Saifullah Z, Khadija G, Fayyaz A, Zaman S, Gul M, Khattak MNK,

Schauer B, Völzke H, Ittermann T. Regional Influence on Iodine Nutritional Status of

Pakistani Pregnant Women. 2017.


deficiency elimination in Pakistan: A global perspective. Journal of Epidemiology. 2017.

6. Khattak RM, Ittermann T, Nauck M, Below H, Völzke H. Monitoring the prevalence of

thyroid disorders in the adult population of Northeast Germany. Population health

metrics. 2016;14(1):39.

7. Naeem M, Khattak RM, ur Rehman M, Khattak MNK. The role of glycated hemoglobin

(HbA1c) and serum lipid profile measurements to detect cardiovascular diseases in type 2

diabetic patients. South East Asia Journal of Public Health. 2016;5(2):30-34.

8. Völzke H, Caron P, Dahl L, De Castro JJ, Erlund I, Gaberšček S, Gunnarsdottir I,

Hubalewska-Dydejczyk A, Ittermann T, Ivanova L, Khattak RM, ........... Ensuring

effective prevention of iodine deficiency disorders. Thyroid. 2016;26(2):189-196.

9. Ittermann T, Khattak RM, Nauck M, Cordova CM, Völzke H. Shift of the TSH reference

range with improved iodine supply in Northeast Germany. European journal of

endocrinology. 2015;172(3):261-267.

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10. Jahangir M, Khattak R, Shahab M, Tauseef I, Khattak M. Prevalence of goiter and iodine

nutritional status in School-age Children of District Karak, Khyber Pakhtunkhwa,

Pakistan. Acta Endocrinologica (1841-0987). 2015;11(3).

11. Saeed S, Jahangir M, Fatima M, Shaikh R, Khattak R, Ali M, Iqbal F. PCR based

detection of Theileria lestoquardi in apparently healthy sheep and goats from two districts

in Khyber Pukhtoon Khwa (Pakistan). Tropical biomedicine. 2015;32(2):225-232.

12. Subhan F, Jahangir M, Saira S, Khattak RM, Shahab M, Haq M, Khattak MNK.


Kohat, Pakistan. South East Asia Journal of Public Health. 2015;4(2):42-46.

13. Saira S, Khattak R, Rehman A, Khan A, Khattak M. Prevalence of goiter and iodine

nutritional status in 6-12 years School-age Children and pregnant women of District

Charsadda, Pakistan. Acta Endocrinologica (1841-0987). 2014;10(1).

14. Ashraf QU, Khan AU, Khattak RM, Ali M, Shaikh RS, Iqbal F. A report on the high

prevalence of Anaplasma sp. in buffaloes from two provinces in Pakistan. Ticks and tick-

borne diseases. 2013;4(5):395-398.

15. Iqbal F, Khattak R, Ozubek S, Khattak M, Rasul A, Aktas M. Application of the reverse

line blot assay for the molecular detection of Theileria and Babesia sp. in sheep and goat

blood samples from Pakistan. Iranian journal of parasitology. 2013;8(2):289.

16. Durrani S, Khan Z, Khattak RM, Andleeb M, Ali M, Hameed H, Taqddas A, Faryal M,

Kiran S, Anwar H. A comparison of the presence of Theileria ovis by PCR amplification

of their ssu rRNA gene in small ruminants from two provinces of Pakistan. Asian Pacific

Journal of Tropical Disease. 2012;2(1):43-47.

17. Khattak R, Rabib M, Khan Z, Ishaq M, Hameed H, Taqddus A, Faryal M, Durranis S,

Gillani Q, Allahyar R. A comparison of two different techniques for the detection of

blood parasite, Theileria annulata, in cattle from two districts in Khyber Pukhtoon Khwa

Province (Pakistan). Parasite: journal de la Société Française de Parasitologie.

2012;19(1):91.

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18. Khattak RM, Ali S, Jahangir M, Khan MN, Rasul A, Iqbal F. Prevalence of ectoparasites

in wild and domesticated grey (Francolinus pondicerianus) and black partridges

(Francolinus francolinus) from Khyber Pakhtoonkhwa Province of Pakistan. Pakistan

Journal of Zoology. 2012;44(5):1239-1244.

19. Gilbert M, Oaks JL, Virani MZ, Watson RT, Ahmed S, Chaudhry M, Arshad M,

Mahmood S, Ali A, Khattak RM. The status and decline of vultures in the provinces of

Punjab and Sind, Pakistan: a 2003 update. Raptors worldwide (Eds: Chancellor, RC &

BU Meyburg) World Working Group on Birds of Prey/MME-BirdLife Hungary.

2004:221-234.

Presentations


deficiency elimination in Pakistan: A global perspective. Paper presented at: 12th Asia

Oceania Thyroid Association Congress 2017; Busan, South Korea.

Posters

1. Khattak RM, Kühn J-P, Lerch MM, Ittermann T, Völzke H. Association of Thyroid

Function with Fat and Iron Contents of Liver; MRI-based Examinations. Paper presented

at: 40th Annual Meeting of the European Thyroid Association 2017; Belgrade, Serbia.

2. Khattak RM, Saifullah Z, Khadija G, Fayyaz A, Zaman S, Gul M, Safdar F, Gul N,

Khattak MNK, Schauer B, Völzke H, Ittermann T. Regional Influence on Iodine

Nutritional Status of Pakistani Pregnant Women. Paper presented at: 12th Asia Oceania

Thyroid Association Congress 2017; Busan, South Korea.

3. Khattak RM, Ittermann T, Nauck M, Below H, Völzke H. Monitoring the Prevalence of

Thyroid Disorders in the Adult Population of Northeast Germany. Paper presented at:

39th Annual Meeting of the European Thyroid Association 2016; Copenhagen, Denmark.

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E. Acknowledgements

My heartiest thanks to Prof. Dr. Henry Völzke for providing me the opportunity to work under

his supervision, and further increasing my research related capabilities. I am obliged to him for

providing the intellectual support in SHIP team and in the international scientific community.

Further thanks for the extending support to my family for staying in Germany and in all other

aspects.

My special thanks to Dr. Till Ittemann for his assistance throughout my stay in Institute for

Community Medicine. He has always been a beacon light throughout the research I conducted in

the Institute for Community Medicine, University Medicine Greifswald, Germany.

My gratitude to all the colleagues in the SHIP team for making my stay comfortable with their

hostile attitude.

I extend my gratitude to my family−particularly my late mom (Noor Jehan), my father (Moweez

Gul Khattak) my wife (Mumtaz Begum) my kids (Noyana Fatma, Hanzala Abdullah Khattak) all

my brothers and sisters and my friends.

I would particularly like to thank Higher Education Commission (HEC) of Pakistan for

providing funding for my stay in Germany for completion of doctoral degree. I would also like to

thank Islamia College Peshawar (Chartered University) and all our funding partners for the

different projects.

Documents

Epidemiology of Iodine Deficiency Disorders in Pakistan ...with spectrophotometric detection. The inter-assay coefficient of variation (CV) was calculated to be 5.6%. Evaluation of