This is a prospective study conducted in Obstetrics and Gynaecology department of IMS and SUM Hospital Bhubaneswar, Odisha, India, during a period from August 2015 till July 2016. Institutional Ethical clearance was taken for this study. Total number of 4031 pregnant females attending OPD for the first time upto 20 weeks during this period was included in this study group after undertaking written consent from them irrespective of their age, parities, BMI, history of infertility or diabetes mellitus or any other risk factors for development of hypothyroidism. Those who were diagnosed to have hypothyroid before pregnancy were also included in this study group. Patients who were diagnosed to have raised TSH in late trimester or untreated were excluded from study. Routine screening of serum TSH and FT4 were performed in all patients of the study group. Previous TSH and FT4 values were collected from those who were pre pregnancy diagnosed cases of hypothyroidism. According to The American Thyroid Association (ATA) guide line those who are diagnosed to have SCH and OH during pregnancy and already pre pregnany diagnosed case of hypothyroid were treated with levothyroxine 1.6 mcg per kg per day and dose was adjusted by 12.5 to 25 mcg increase every 4 to 6 weeks until the patient was euthyroid and serum TSH returned normal as per consultation with Endocrinology unit. These patients were followed up till deliveries and their adverse obstetrical outcomes were recorded as development of PIH, LBW, Oligohydramnios, association with GDM, PPROM and NICU admission. These adverse outcomes were compared with similar types of complications developed in 3213 number of pregnant ladies delivered in our hospital from August 2015 till July 2016 excluding those treated hypothyroid patients taken as control group.

Subclinical hypothyroidism is defined as raised thyrotropin combined with a normal serum free thyroxine level. The ATA 2011 and Endocrine Society (ES) 2012 guidelines recommended that the normal thyrotropin reference range should be 0.1-2.5miu/ml in first trimester, 0.2-3miu/ml, .3-3.5miu/ml in second and third trimester respectively [2,16]. The ATA, ES, AACE (American Association of Clinical Endocrinologist) have recommended and generally accepted that any pregnant women having thyrotropin above 10miu/ml and normal thyroxin level should be diagnosed as overt Hypothyroidism [2,16,17]. Subclinical hypothyroidism is a biochemical diagnosis and cannot be based upon patient’s symptoms, hence routine TSH screening is best method for diagnosis of hypothyroidism. Worldwide endemic iodine deficiency accounts for most cases of hypothyroidism in pregnant women while chronic autoimmune thyroiditis is the most common cause of hypothyroidism in iodine sufficient parts of the world [18].

In this one year study 256 pregnant ladies were diagnosed to have hypothyroid by routine screening of TSH and FT4 by chemi illumisence method (CLA) by Roch Cobas 411e in our Hospital’s central laboratory up to 20 weeks of gestation irrespective of their gravida. CLA is more sensitive as well as more specific for monitoring thyrotropin [19,20]. All diagnosed cases of hypothyroid pregnant ladies were treated with levothyroxine dosage adjusted by Endocrinologist and were followed up with serum TSH and FT4, in 4 to 8 week intervals. Out of 256 patients 38 were lost follow up and ultimately 218 hypothyroid pregnant females were followed up till deliveries and their outcomes were recorded. Total number of deliveries in our hospital in one year was 3431 and the incidence of hypothyroidism in pregnancy was calculated to be 6.35%.

Statistical significance was taken at the 0.05 value. Categorical variables were compared using the χ² test and Fisher’s-exact test was used when there were few observations. A p-value for PIH, GDM, Oligohydramnios, PPROM developed in hypothyroid pregnant ladies which were calculated by Yates corrected Chi-square and Fisher’s-exact test from open epic version 3.03a.

In our study [Table/Fig-1], indicates the incidence of adverse obstetrical outcomes in the treated hypothyroid pregnant ladies as well as incidence of similar adverse outcome among all delivered patients. Out of these 184 was Sub Clinical Hypothyroid and 34 were Overt Hypothyroid. Incidence of PIH, GDM, Oligohydramnios, PPROM, NICU admissions were higher among hypothyroid pregnant women though adequately treated with levothyroxine than the total delivered pregnant women (3213). But incidence of LBW babies were less and no one had developed PET or Eclampsia, abruption and IUD among the treated group while incidence of PET and Eclampsia was 2.3% in control group. Incidence of PIH and GDM were very high (16% and10% respectively) in treated thyroid group than the control (5.3% and1.27% respectively). Two cases of abortion were documented while not a single case of IUD was documented among treated women.

In our study rate of cesarean section was more in treated thyroid group [Table/Fig-2].

[Table/Fig-3] indicates that among the hypothyroid patients 184 were SHC and 34 were OH whose TSH were >10miu/ml or above the trimester specific reference with decrease FT4 level. Comparing the adverse obstetric outcomes between SCH and OH, the incidence of LBW is almost equal in both the groups while associations of GDM and PIH incidence are more among OH. Considering the age group for hypothyroidism among pregnant women is higher between 26- 30 years because maximum pregnant ladies were in this age group according to hospital records.

Our study shows the p-value for PIH, GDM, Oligohydraminos, PPROM developed in hypothyroid pregnant ladies which were calculated by Yates corrected chi-square and Fisher’s-exact test from open epic version 3.03a. A p-value was significant (<0.001) for PIH, GDM, PPROM and oligohydramnios but insignificant for low birth weight [Table/Fig-4].

Pregnancy has a profound impact on thyroid gland and its functions which warrants universal screening for hypothyroidism in all pregnant women. Hypothyroidism poses special risk for both pregnant women and her developing foetus. Early detection by screening all pregnant ladies with TSH and treating them with levothyroxine can be able to prevent complications to some extent. It is better to screen for hypothyroid both pregnant women and those who wants to be pregnant as thyroid hormone status is directly related to foetal brain development.

In different prospective studies the prevalence of undiagnosed subclinical hypothyroidism ranges from 3 to 15 % [21]. In International evidences, the estimated prevalence of hypothyroidism in pregnancy was 2-3% [22,23]. Of these, 0.3-0.5% is OH and 2-2.5% is SCH [24]. Prevalence of hypothyroidism in pregnancy in Indian population is 4.8-12% [24]. Reported prevalence by Sahu et al., in 2010 was 6.47% with 4.58% as OH [25]. Another Indian study has reported the prevalence of hypothyroidism to be 12%, of which 3% was OH and 9% was SCH [26]. In our study the incidence of hypothyroidism was 6.35% of which 5.35% was SCH and1.01% was OH which indicates higher prevalence of SCH and OH like other Indian studies.

Though the previous data suggests hypothyroid mothers have increased incidence of pregnancy related complications if it is not corrected or inadequately treated [11,12,27], but no data suggests reduced or increased risk of complications in adequately treated SCH/OH mothers. However, one study Matalon S et al., had shown increase risk of caesarean section in cases with adequately treated hypothyroidism [28]. A register based study without estimate of treatment adequacy found increase risk for preeclampsia, diabetes, preterm births, caesarean section, and labour inductions among those on levothyroxine use [29]. Study done by Avalovich et al., in inadequately treated hypothyroid pregnant mother the incidence of preterm deliveries was 20% among OH and 7.2% among SCH [5]. But in our study with adequately treated mother incidence of PPROM leading to preterm deliveries are almost equal in both OH and SCH (5.9 in SCH and 5.8 in OH). This implies the incidence of preterm is reduced in controlled patient. Similarly study done by Leung et al., incidence of PIH was 36% in OH and 25% in SCH among untreated hypothyroid mother while in our study in controlled patient incidence of PIH was 23.5% and 14.6% in OH and SCH respectively which is reduced incidence among treated patients [12].

The most common endocrinology problems during pregnancy are GDM and hypothyroidism. Approximately 1.1 to 14.3% of pregnant ladies suffer from GDM and hypothyroidism affects 2.6 to 6.4% of them [30]. In our study there was clear-cut association of increased incidence of GDM among hypothyroid and that to higher among OH (17.6%).

Sample size was small and it could have been better to compare the obstetric complications between treated and untreated pregnant women.

It has already been proved that thyroid diseases are associated with various obstetrical, labor and delivery complications. ATA and ES have already recommended routine TSH screening in all pregnant women but we lack the information whether all these adverse pregnancy outcomes can be avoided by adequately treating hypothyroid pregnant women with levothyroxine or not. We concluded from our study that even if pregnancy with hypothyroidism adequately treated with levothyroxine, development of adverse outcomes cannot be totally prevented. However incidence of PIH, Preterm delivery can be reduced as well as severe form of PIH (PET and Eclampsia), IUD and Abruptio placentae can be prevented among controlled hypothyroid pregnant women. All hypothyroid pregnant women must be screened for GDM as incidence of GDM is higher among them. However, further researches are needed to prove the fact.