**3.1 Thyroid hormones and its effects on obstetric outcome**

Various studies have registered in their findings that placenta has strong affinity for T3 and is dependent on thyroid hormones for its growth. Triiodothyronine/ T3 is plays a significant role in placental trophoblastic growth by its likely effect on growth factors like EGF (epidermal growth factor) and hormone like 17 beta estradiol [19, 24, 25]. Small for gestational age babies (SGA) and intra uterine growth retardation of fetus (IUGR) are most likely results of impaired growth of placental trophoblasts [26, 27]. Fetal thyroid hormones have been found to be decreased in IUGR babies compared to gestation matched normal fetal serum. Inflammation associated with impaired uteroplacental circulation are registered to be causative factors for development of serious disorders like eclampsia and preeclampsia in pregnancy. These situations are also documented to be associated with increased oxidative stress by various studies [28]. Hence various studies now put inflammation under major focus in development of preeclampsia and pre-term labor in pregnancy. Thyroid hormones act on DNA and regulate expression of various genes which also includes genes associated with inflammation. As inflammation is now considered to be an important causative factor for development of pre-eclampsia, thyroid hormones are also corroborated by various studies to be responsible for this [29]. Analysis of maternal and cord blood has validated this hypothesis and revealed a low T4 with raised TSH level in preeclampsia cases which has also been linked with placental inadequacy.

Various studies have also found an association of gestational diabetes mellitus (GDM) with impaired thyroid status. Inverse correlation between metformin and TSH value further strengthens this association. Thus, screening of all pregnant women for thyroid function along with anti TPO antibody measurement has been advised by many studies, particularly in "at risk "cases of GDM [30–33]. Both thyroid dysfunction and diabetes mellitus are known to adversely affect obstetric and fetal outcome and now gradually gathering data proves that very often both the conditions coexist in pregnancy depicting an association between them and hence early screening, intervention and timely management is advocated by various studies [34–37].

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planned pregnancy.

*Autoimmune Basis of Sub Clinical Hypothyroidism in Pregnancy*

**3.2 Pregnancy and clinical/subclinical hypothyroidism**

This also results in increased need of iodine in pregnancy.

**3.3 Hypothyroidism and autoimmunity in pregnancy**

symptoms of autoimmune disease [41].

The need for iodine increases in pregnancy (daily requirement of

Indian population with greater prevalence of anti TPO antibody positivity.

High TSH level with normal T4 level is known as subclinical hypothyroidism (SCH). Subclinical hypothyroidism is one of the most common type of thyroid dysfunction that is found to be associated with pregnancy [38, 39]. The increased need of thyroid hormones to meet the extra demand by the growing fetus in the first 12 weeks of gestation is dealt by hCG due to its thyrotrophic action as discussed earlier and also via hypothalamus-pituitary-thyroid axis regulation which usually results in small painless enlargement, i.e., goiter formation in pregnant women [1].

Hence, endemic areas of iodine deficiency have shown a higher prevalence of clinical or subclinical hypothyroidism in general and in particular in pregnant women. Because of increased thyroid hormone production, increased renal iodine excretion, and fetal iodine requirements, dietary iodine requirements are higher in pregnancy than they are for non-pregnant adults. The requirement of iodine is 250 μg/day in pregnancy. Recommendation by American Thyroid Association (ATA) is women who are planning pregnancy or currently pregnant, should supplement their diet with a daily oral supplement that contains 150μg of iodine in the form of potassium iodide [40]. This should optimally start 3 months in advance of

However, apart from iodine deficiency, the other most significant cause of hypothyroidism in recent times is presence of anti thyroperoxidase antibody, i.e., anti TPO antibody and anti Tg (anti thyroglobulin) antibody in the serum. The thyroperoxidase enzyme as described above is highly essential for oxidation of trapped iodine and its incorporation into tyrosine molecule for synthesis of thyroxin. Anti TPO antibody destroys the thyroperoxidase enzyme and hence prevents the iodination of tyrosine molecule and overall synthesis of thyroxin is hampered resulting in hypothyroidism. This autoimmune basis of hypothyroidism is now more relevant after iodine deficiency has been tackled by fortification of food products with iodine/with iodine supplementation as potassium iodide. In pregnancy, immune regulatory cytokines and cells are present in the mother's circulatory system and accumulate in the decidua and can modify autoimmune responses influencing the

Presence of anti-TPO antibody is a major risk factor for progression to overt hypothyroidism. Various studies reveal a prevalence of 2–17% of euthyroid pregnant women being anti-TPO antibody positive. Still data from Indian scenario is extremely limited. TPO antibodies are able to cross the placenta. At the time of delivery, cord blood anti TPO Ab levels strongly correlate with third-trimester

iodine −150–200 μg/day, 250 μg/day in pregnancy) leading to an iodine deficient status if not adequately supplemented. Apart from iodine deficiency, the other most common factor for thyroid hormone deficiency has been attributed to anti-TPO antibodies. Hypothyroidism is registered to be more prevalent in Asian countries compared to their Western counterparts. As such thyroid disorders have wide geographical variations attributed to dietary factors, level of various goitrogens in diet and their consumption level, deficiencies of micronutrients like selenium, iron and most importantly iodine. Autoimmune thyroid diseases are also more prevalent in Asian countries and accumulating literatures suggest it to be more substantial in

*DOI: http://dx.doi.org/10.5772/intechopen.88508*

*Goiter - Causes and Treatment*

mothers has also been documented [23].

linked with placental inadequacy.

**3.1 Thyroid hormones and its effects on obstetric outcome**

Various studies have registered in their findings that placenta has strong affinity

Various studies have also found an association of gestational diabetes mellitus (GDM) with impaired thyroid status. Inverse correlation between metformin and TSH value further strengthens this association. Thus, screening of all pregnant women for thyroid function along with anti TPO antibody measurement has been advised by many studies, particularly in "at risk "cases of GDM [30–33]. Both thyroid dysfunction and diabetes mellitus are known to adversely affect obstetric and fetal outcome and now gradually gathering data proves that very often both the conditions coexist in pregnancy depicting an association between them and hence early screening, intervention and timely management is advocated by various

for T3 and is dependent on thyroid hormones for its growth. Triiodothyronine/ T3 is plays a significant role in placental trophoblastic growth by its likely effect on growth factors like EGF (epidermal growth factor) and hormone like 17 beta estradiol [19, 24, 25]. Small for gestational age babies (SGA) and intra uterine growth retardation of fetus (IUGR) are most likely results of impaired growth of placental trophoblasts [26, 27]. Fetal thyroid hormones have been found to be decreased in IUGR babies compared to gestation matched normal fetal serum. Inflammation associated with impaired uteroplacental circulation are registered to be causative factors for development of serious disorders like eclampsia and preeclampsia in pregnancy. These situations are also documented to be associated with increased oxidative stress by various studies [28]. Hence various studies now put inflammation under major focus in development of preeclampsia and pre-term labor in pregnancy. Thyroid hormones act on DNA and regulate expression of various genes which also includes genes associated with inflammation. As inflammation is now considered to be an important causative factor for development of pre-eclampsia, thyroid hormones are also corroborated by various studies to be responsible for this [29]. Analysis of maternal and cord blood has validated this hypothesis and revealed a low T4 with raised TSH level in preeclampsia cases which has also been

of thyroid hormones in pregnancy as the developing fetus is completely dependent on maternal thyroid hormones till 12 weeks of gestation. Hence, the gland becomes over stimulated and hyperactive to secrete more T4 and T3 to meet the increased demand and this is brought about through hypothalamus-pituitary-thyroid axis regulatory mechanisms. Thyroxin and TBG (thyroid binding globulins) levels rise in pregnancy along with a simultaneous decrease in TSH (thyroid stimulating hormone) level [13]. A placental deiodinase enzyme also results in more thyroid hormone synthesis in pregnancy [14–16]. hCG is known to have a TSH simulating effect and hence attributes to raise the thyroid hormone synthesis to meet the increased demand via its thyrotrophic effect [17]. Absolute fetal dependency on mother's thyroid hormones can result in adverse obstetric and fetal outcome if the increased demand for T4 and T3 is not met adequately in the first 12 weeks of gestation [18]. There has also been documented evidences that proper placental development is also dependent on thyroid hormones and lack of it can result in improper placenta formation [19] with adverse obstetric outcomes like abruptio placentae, preeclampsia, miscarriages, preterm delivery, low birth weight (LBW), IUGR (intrauterine growth retardation) and small for gestational age babies (SGA) [20–22]. Impaired intellectual development of off springs of hyper/hypothyroid

**18**

studies [34–37].
