Zdenka Limanova

Thyroid in pregnancy: From physiology to screening

Abstract Thyroid hormones are crucial for the growth and maturation of many target tissues, especially the brain and skeleton. During critical periods in the first trimester of pregnancy, maternal thyroxine is essential for fetal development as it supplies thyroid hormone-dependent tissues. The ontogeny of mature thyroid function involves organogenesis, and maturation of the hypothalamus, pituitary and the thyroid gland; and it is almost complete by the 12th–14th gestational week. In case of maternal hypothyroidism, substitution with levothyroxine must be started in early pregnancy. After the 14th gestational week, fetal brain development may already be irreversibly affected by lack of thyroid hormones. The prevalence of manifest hypothyroidism in pregnancy is about 0.3–0.5%. The prevalence of subclinical hypothyroidism varies between 4 and 17%, strongly depending on the definition of the upper TSH cutoff limit. Hyperthyroidism occurs in 0.1–1% of all pregnancies. Positivity for antibodies against thyroid peroxidase (TPOAb) is common in women of childbearing age with an incidence rate of 5.1–12.4%. TPOAb-positivity may be regarded as a manifestation of a general autoimmune state which may alter the fertilization and implantation processes or cause early missed abortions. Women positive for TPOAb are at a significant risk of developing hypothyroidism during pregnancy and postpartum. Laboratory diagnosis of thyroid dysfunction during pregnancy is based upon serum TSH concentration. TSH in pregnancy is physiologically lower than the non-pregnant population. Results of multiple international studies point toward creation of trimester-specific reference intervals for TSH in pregnancy. Screening for hypothyroidism in pregnancy is controversial and its implementation varies from country to country. Currently, the case-finding approach of screening high-risk women is preferred in most countries to universal screening. However, numerous studies have shown that one-third to one-half of women with thyroid disorders escape the case-finding approach. Moreover, the universal screening has been shown to be more cost-effective. Screening for thyroid disorders in pregnancy should include assessment of both TSH and TPOAb, regardless of the screening approach. This review summarizes the current knowledge on physiology of thyroid hormones in pregnancy, causes of maternal thyroid dysfunction and its effects on pregnancy course and fetal development. We discuss the question of case-finding versus universal screening strategies and we display an overview of the analytical methods and their reference intervals in the assessment of thyroid function and thyroid autoimmunity in pregnancy. Finally, we present our results supporting the implementation of universal screening.

Recommendations on prenatal screening and the connections to other diseases such as thyroid dysfunction

Abstract The aim of general maternal-foetal care is to ensure an uncomplicated birth of a healthy baby to a healthy mother. There is a large range of screening tests used during pregnancy: for gestational diabetes, infection, rhesus-D status, thyroid dysfunction, as well as other tests. An important part of prenatal care is the screening of major aneuploidies, primarily for Down’s syndrome. This screening is possible in either the first or second trimester, or in both. Management of this type of screening is very similar around the world. Hypothyroidism can affect the psychomotor development of the child. Thyroid-stimulating hormone (TSH), autoantibodies against thyroperoxidase (TPOAb), and free thyroxin (FT4) were determined within our group of 7530 pregnant women. Elevated concentrations of TSH were found in 5.1%, suppression was found in 2.9% and 11.5% were TPOAb positive. Either a familial or personal history of thyroid or autoimmune diseases was present in 58.3% of those women who tested positive on any thyroid test. At minimum, 40% of women TPOAb positive during pregnancy have some kind of thyroid disorders after delivery. These results support the efficacy of general thyroid function screening in early pregnancy, as well as the follow-up after delivery of those women who are positive.

Thyroid in Pregnancy

Many changes in the functioning of the thyroid gland occur during pregnancy and some diseases of the thyroid gland can affect both the pregnant woman and the fetus. (Casey et all., 2006; Lazarus & Premawardhana, 2005; Poppe et all., 2007). Hypothyroidism is the most serious disorder of those occurring during pregnancy, and it might go unnoticed as some ‘nonspecific’ problem. Pregnant women with subclinical hypothyroidism seem to escape early clinical detection (Lazarus, 2002). While the hyperfunction during pregnancy usually manifests itself by clinical symptoms or a relapse of a previously cured disease (mostly Graves Basedow) (Abalovich et all., 2007), lowered functioning is much more dangerous because of its non-specific symptoms. During the 1st trimester, the fetus is completely dependent upon thyroxin produced by the mother (Smallridge & Landerson, 2001). Even a small unnoticed malfunction of the thyroid gland, which doesn’t have to endanger the course of the pregnancy, can affect the psychomotor developement of the child (Morreale de Escobar et all., 2004; Mitchell & Klein, 2004)). Some women with subclinical hypothyroidism are absolutely asymptomatic and there is no reliance on the clinical image, while diagnostic of thyroid dysfunction (Klein et all., 2001). Malfunction of the thyroid gland during pregnancy is long-term, and still not a sufficiently solved problem (Lazarus, 2002). On many pages of scientific literature and specialist literature there are still new arguments to systematically screen pregnant women for thyroid dysfunction and asymptomatic chronic thyroiditis in order to give such women the appropriate treatment (Surks et all., 2004). Results of surface population screenings are slightly varied, depending upon on level of medical care and approach to prevention, geographical conditions, supplementing with iodine, and other circumstances (including used diagnostic criteria) (Vaidya et all., 2007). Evaluating thyroidal function during pregnancy is difficult, considering the other differing influences of pregnancy. Guidelines for management of thyroid dysfunction during pregnancy and postpartum (Abalowich et al. 2007) recommend not universal but only case finding screening. The first aim of the study was to assess the value of this recommendation. The other aim was to introduce an estimation of thyroid dysfunction during pregnancy, selection of suitable biochemical markers and determination of reference intervals for these markers in pregnancy.

Universal Screening for Thyroid Disorders in Pregnancy: Experience of the Czech Republic

The role of the thyroid gland in pregnancy and the impact of thyroid disorders on the course of pregnancy and development of the offspring have drawn a considerable interest in the recent years, both in the medical and in the general society. About 10% of pregnant women are positive for autoantibodies against thyroperoxidase (TPOAb) (Glinoer 2007, Lazarus and Kokandi 2000, Springer 2009) and between 2 and 4% suffer subclinical or overt hypothyroidism (Casey 2005; Vaidya 2007, Springer 2009). Dysfunction of the maternal thyroid in pregnancy adversely affects the course of pregnancy and the psychomotor development of the offspring (Haddow 1999, Morreale de Escobar 2004). According to recent findings, even the mere positivity of TPOAb without concomitant thyroid dysfunction in pregnant women may have a negative impact on the psychomotor development of the child (Li 2010). Furthermore, up to one half of the TPOAb-positive (TPOAb+) pregnant women develop postpartum thyroiditis (PPT) which can lead to persistent hypothyroidism in about one third of women (Lazarus and Premawardhana 2008). According to recent findings of Stagnaro-Green, this proportion may be even much higher and persistent hypothyroidism may affect up to one-half of women with history of PPT (Stagnaro-Green 2011b). If unrecognised and untreated, late postpartum thyroid dysfunction, in most cases subclinical (SH) or overt hypothyroidism (OH) may have a longterm negative effect not only on the mother s health, but also on the next pregnancies.