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Hypothyroidism and Pregnancy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Obstetrik)ORCID iD: 0000-0002-6311-9506
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hypothyroidism is a common endocrine disorder affecting women of reproductive age. On a global level, iodine deficiency is still the most common cause of hypothyroidism. Also genetic variations, in particular SNP rs4704397 in the PDE8B gene, are responsible for a significant proportion of TSH variations.  Untreated hypothyroidism has significant adverse effects on pregnancy and fetal outcome. Most international guidelines suggest targeted thyroid testing in pregnant women with risk factors for thyroid disturbances.

In a case-control study, an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage was found. The explanation for this association is unknown.

In a nationwide survey, all guidelines for thyroid testing and management of hypothyroidism during pregnancy in Sweden were collected and compared with international guidelines. The local guidelines were variable and poorly compliant with the international guidelines.

In a follow-up in one district, 5,254 pregnant women were included for subsequent review of their medical reports. We found a targeted thyroid testing rate of 20.1% in clinical practice, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More disturbingly, half of the women who were on levothyroxine treatment at the time of conception had an elevated TSH level at thyroid testing.

In a subsequent cohort study of the 5,254 women, we found the prevalence of trimester-specific elevated TSH and overt hypothyroidism to be equal in targeted thyroid tested and untested women.

In a cross-sectional study, a median urinary iodine concentration (UIC) of 98 μg/l was found in the study population. According to WHO/UNICEF/IGN criteria, the population-based median UIC during pregnancy should be 150-249 μg/l.

In conclusion, genetic variations may contribute to adverse pregnancy outcomes. In clinical practice, thyroid testing and the management of hypothyroidism during pregnancy is unsatisfactory, regarding the whole chain from development of local guidelines to their implementation and to targeted thyroid testing. Moreover, our results indicate insufficient iodine status in the pregnant population of Sweden.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. , 69 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1081
Keyword [en]
phosphodiesterase 8B, recurrent miscarriage, single nucleotide polymorphism, thyroid, guidelines, hypothyroidism, pregnancy, survey, thyroid testing, screening, iodine, iodine deficiency, median urinary iodine concentration
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
URN: urn:nbn:se:uu:diva-247090ISBN: 978-91-554-9201-4 (print)OAI: oai:DiVA.org:uu-247090DiVA: diva2:796119
Public defence
2015-05-08, Rosénsalen, Akademiska sjukhuset, ingång 95/96. Barn- och kvinnosjukhuset. NBV (nedre bottenvåning)., Uppsala, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-04-17 Created: 2015-03-13 Last updated: 2015-07-07
List of papers
1. Phosphodiesterase 8B gene polymorphism in women with recurrent miscarriage: A retrospective case control study.
Open this publication in new window or tab >>Phosphodiesterase 8B gene polymorphism in women with recurrent miscarriage: A retrospective case control study.
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2012 (English)In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 13, 121- p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Recurrent miscarriage affects approximately 1% of all couples. There is a known relation between hypothyroidism and recurrent miscarriage. Phosphodiesterase 8B (PDE8B) is a regulator of cyclic adenosine monophosphate (cAMP) with important influence on human thyroid metabolism. Single nucleotide polymorphism (SNP) rs 4704397 in the PDE8B gene has been shown to be associated with variations in serum Thyroid Stimulating Hormone (TSH) and thyroxine (T4) levels. The aim of this study was to investigate whether there is an association between the SNP rs 4704397 in the PDE8B gene and recurrent miscarriage. METHODS: The study was designed as a retrospective case control study. 188 cases with recurrent miscarriage were included and compared with 391 controls who had delivered at least once and with no history of miscarriage or assisted reproduction. RESULTS: No difference between cases and controls concerning age was found. Bivariate associations between homozygous A/A (OR 1.57, 95% CI 0.98-2.52) as well as G/G carriers (OR 1.52, 95% CI 1.02-2.25) of SNP rs 4704397 in PDE8B and recurrent miscarriage were verified (test for trend across all 3 genotypes, p = 0.059). After adjustment for known confounders such as age, BMI and smoking the association between homozygous A/A (AOR 1.63, 95% CI 1.01 - 2.64, p = 0.045) and G/G (AOR 1.52, 95% CI 1.02 - 2.27, p = 0.039) carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage remained. CONCLUSIONS: Our findings suggest that there is an association between homozygous A/A as well as homozygous G/G carriers of SNP rs 4704397 in PDE8B and recurrent miscarriage.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-188671 (URN)10.1186/1471-2350-13-121 (DOI)000314113200001 ()23237535 (PubMedID)
Available from: 2012-12-18 Created: 2012-12-18 Last updated: 2017-12-06Bibliographically approved
2. Thyroid Testing and Management of Hypothyroidism During Pregnancy: A Population-based Study
Open this publication in new window or tab >>Thyroid Testing and Management of Hypothyroidism During Pregnancy: A Population-based Study
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2013 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 98, no 7, 2687-2692 p.Article in journal (Refereed) Published
Abstract [en]

Context: There are international guidelines on thyroid function testing and management of hypothyroidism during pregnancy. Few studies have evaluated how they are implemented into clinical practice. Objective: In this descriptive study, we assessed the implementation of international guidelines in this field into local guidelines and also into clinical practice. Design and Participants: In a nationwide survey, all guidelines in Sweden were collected (n = 29), and the adherence of the local guidelines to The Endocrine Society Guidelines 2007 was evaluated. In a follow-up in 1 district, 5254 pregnant women with an estimated date of delivery between January 1, 2009, and December 31, 2011, were included for subsequent review of their medical reports. Results: All but 1 district had guidelines on the subject. All local guidelines included fewer than the 10 listed reasons for thyroid testing recommended by The Endocrine Society Guidelines. Furthermore, most guidelines recommended additional types of thyroid function tests to TSH sampling and lower trimester-specific TSH upper reference limits for women on levothyroxine treatment (P < .001). In the follow-up, the thyroid testing rate was 20%, with an overall frequency of women with trimester-specific elevated TSH of 18.5%. More than half of the women (50.9%) who were on levothyroxine treatment at conception had an elevated TSH level at thyroid testing according to The Endocrine Society Guidelines. Conclusions: The local guidelines are variable and poorly compliant with international guidelines. Performance of thyroid testing is not optimal, and rates of elevated TSH at testing are extremely high in subgroups.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-208672 (URN)10.1210/jc.2013-1302 (DOI)000322780600030 ()
Available from: 2013-10-07 Created: 2013-10-07 Last updated: 2017-12-06Bibliographically approved
3. Targeted Thyroid Testing During Pregnancy in Clinical Practice
Open this publication in new window or tab >>Targeted Thyroid Testing During Pregnancy in Clinical Practice
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2014 (English)In: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 124, no 1, 10-15 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:To evaluate the efficacy of a targeted thyroid testing approach during pregnancy in clinical practice.

METHODS:This is a retrospective cohort study performed within Uppsala County, Sweden. Data were derived from the population-based Uppsala Biobank of Pregnant Women, in which blood samples are collected in conjunction with the routine ultrasound screening in gestational week 17-19. For this study, 5,254 pregnant women with an estimated date of delivery between January 1, 2009, and December 31, 2011, were included. On review of their medical records, women who were tested for thyroid dysfunction during pregnancy in clinical practice were identified (n=891). From the remaining untested women, 1,006 women were randomly selected for analyses of thyrotropin (TSH), free thyroxine levels, and thyroid peroxidase antibodies. Thyroid-stimulating hormone levels in both groups were analyzed with regard to trimester-specific upper reference levels as recommended by the International Endocrine Society Guidelines.

RESULTS:The proportion of trimester-specific TSH elevation was 12.6% in the targeted thyroid testing group and 12.1% in the untested group (P=.8; odds ratio [OR] 1.04, 95% confidence interval [CI] 0.79-1.37). The proportion of overt hypothyroidism was 1.1% and 0.7% in the groups, respectively (P=.4; OR 1.57, 95% CI 0.55-4.45).

CONCLUSIONS:The prevalence of trimester-specific elevated TSH and overt hypothyroidism was equal in targeted thyroid tested and untested women. When implemented in clinical practice, targeted thyroid testing is unsatisfactory. If ongoing studies provide support for treatment of pregnant women with elevated TSH, universal thyroid testing appears the most reasonable approach.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-228696 (URN)10.1097/AOG.0000000000000344 (DOI)000337734000004 ()
Available from: 2014-07-21 Created: 2014-07-21 Last updated: 2017-12-05Bibliographically approved
4. Iodine deficiency in a study population of pregnant women in Sweden
Open this publication in new window or tab >>Iodine deficiency in a study population of pregnant women in Sweden
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2015 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 94, no 11, 1168-1174 p.Article in journal (Refereed) Published
Abstract [en]

Introduction

Iodine deficiency in utero may impair neurological development of the fetus. In Sweden, iodine nutrition is considered to be adequate in the general population. The aim of this study was to evaluate iodine nutrition during pregnancy in Sweden.

Material and methods

In this cross-sectional study, the total study population (= 459) consisted of two cohorts (Värmland County, = 273, and Uppsala County, = 186) of pregnant non-smoking women without pre-gestational diabetes mellitus or known thyroid disease before or during pregnancy. Spot urine samples were collected in the third trimester of pregnancy for median urinary iodine concentration (UIC) analysis.

Results

The median UIC in the total study population was 98 μg/L (interquartile range 57–148 μg/L).

Conclusions

According to WHO/UNICEF/IGN criteria, population-based median UIC during pregnancy should be 150–249 μg/L. Thus, our results indicate insufficient iodine status in the pregnant population of Sweden. There is an urgent need for further assessments in order to optimize iodine nutrition during pregnancy.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-247420 (URN)10.1111/aogs.12713 (DOI)000362844400004 ()26292156 (PubMedID)
Available from: 2015-03-18 Created: 2015-03-18 Last updated: 2017-12-04Bibliographically approved

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