“AN ANALYTICAL CROSS-SECTIONAL STUDY ON HYPOTHYROIDISM IN
PREGNANCY, ITS MATERNAL AND FETAL OUTCOME”
Dissertation submitted to
THE TAMILNADU Dr.M.G.R MEDICAL UNIVERSITY In partial fulfilment of the requirement
for the award of
M.S.DEGREE – BRANCH – II
OBSTETRICS AND GYNAECOLOGY
GOVT. KILPAUK MEDICAL COLLEGE, KILPAUK, CHENNAI
MAY- 2019
BONAFIDE CERTIFICATE
This is to certify that the dissertation entitled “AN ANALYTICAL CROSS SECTIONAL STUDY ON HYPOTHYROIDISM IN PREGNANCY, ITS MATERNAL AND FETAL OUTCOME” is the bonafide original work of Dr.S.VINODHINI under the guidance of Dr.T.S.MEENA M.D, DGO., Professor of Department of Obstetrics and Gynaecology, KMCH, Chennai in partial fulfilment of the requirements for MS Obstetrics and Gynaecology branch II examination of the Tamilnadu Dr.M.G.R. Medical university to be held in MAY 2019. The period of Postgraduate study and training is from May 2016 to May 2019.
Prof. Dr.P. VASANTHAMANI, MD, DGO, MNAMS, DCPSY, MBA, THE DEAN,
Government Kilpauk Medical College and Hospital, Chennai-600010
Dr.T.S.MEENA M.D, DGO,
PROFESSOR,Department of Obstetrics and Gynaecology, Govt Kilpauk Medical College and Hospital Chennai – 600 010
Dr.K.L.MALARVIZHI, M.D.,DGO.,DNB., PROFESSOR & HOD,
Department of Obstetrics and Gynaecology, Govt Kilpauk Medical College and Hospital Chennai – 600 010
DECLARATION
I solemnly declare that this dissertation “AN ANALYTICAL CROSS- SECTIONAL STUDY ON HYPOTHYROIDISM IN PREGNANCY, ITS MATERNAL AND FETAL OUTCOME” was prepared by me at Government Kilpauk Medical College and Hospital, Chennai, under the guidance and supervision of Dr.T.S.MEENA M.D, DGO, Professor, Department of Obstetrics and Gynaecology, Government Kilpauk Medical College and Hospital, Chennai. This dissertation is submitted to The Tamil Nadu Dr.M.G.R. Medical University, Chennai in partial fulfillment of the University regulations for the award of the degree of M.S. (Obstetrics and Gynaecology).
Place: Chennai
Date: (Dr.S. VINODHINI)
ACKNOWLEDGEMENT
I take this opportunity to express our gratitude to all those who have been instrumental in the successful completion of project either directly or indirectly.
I express my sincere thanks to Prof. Dr.P.VASANTHAMANI MD, DGO, MNAMS, DCPSY, MBA, Dean, Government Kilpauk Medical College for allowing me to conduct the study using the available facilities.
I convey my heartfelt gratitude and sincere thanks to our HOD Dr.K.L.MALARVIZHI, M.D., DGO, DNB, Department of Obstetrics and Gynaecology, Kilpauk Medical College for her constant support and guidance throughout the course of my study and preparation of the dissertation.
I convey my heartfelt gratitude and sincere thanks to my guide
Dr.T.S.MEENA M.D, DGO., Professor, Department of Obstetrics and
Gynaecology, Kilpauk Medical College who with her exhaustive knowledge and
Professional expertise has provided able guidance and constant encouragement
throughout the preparation of this dissertation.
I take this opportunity to express my deep sense of gratitude and humble regards to my beloved teacher prof Dr.M.S.SORNAM, MD., DGO and Prof.
Dr.S.USHARANI, M.D.,DGO.,DNB for being a constant source of inspiration and support.
I am grateful to my Professors, Assistant Professors, colleagues and my friends for their advice and suggestions.
My heartful thanks to my family and friends, who have been a constant source of encouragement and immense help, for instilling in me a sense of commitment and for their belief in me.
Last but not the least I thank all my Patients, who formed the backbone of this study without whom this study would not have been possible.
(Dr. S. VINODHINI)
ABBREVIATIONS TPO - THYROID PERXOIDISE
Tg- THYROGLOBULIN
TBG-THYROXINE-BINDING GLOBULIN T3 -TRI IODO TYRONINE
T4 -TETRA IODO TYRONINE fT3 - FREE T3
fT4 - FREE T4 rT3 - REVERSE T3
MIT-MONOIODOTYROSINE DIT-DIIODOTYROSINE
TFT - THYROID FUNCTION TEST
TSH- THYROID STIMULATING HORMONE
TRH- THYROTROPIN RELEASING HORMONE
βhCG -β HUMAN CHORIONIC GONADOTROPHIN PPT - POSTPARTUM THYROIDITIS
FNAC- FINE NEEDLE ASPIRATION CYTOLOGY PROM- PRELABOUR RUPTURE OF MEMBRANES LSCS- LOWER SEGMENT CESAEREAN SECTION EPO- ERYTHROPOIETIN
GDM-GESTATIONAL DIABETES MELLITUS IUD-INTRA UTERINE DEATH
WHO-WORLD HEALTH ORGANISATION
AACE- AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS ACOG- AMERICAN COLLEGE OF OBSTETRICS AND GYNAECOLOGY ITS -INDIAN THYROID SOCIETY
RCOG- ROYAL COLLEGE OF OBSTETRICS AND GYNAECOLOGY
CONTENTS
S.NO TITLE PAGE NO
1 INTRODUCTION 1
2 AIM OF THE STUDY 3
3 REVIEW OF LITERATURE 4
4 MATERIALS AND METHODS 46
5 OBSERVATION AND ANALYSIS 51
6 DISCUSSION 70
7 CONCLUSION 78
8 BIBLIOGRAPHY 79
9 ANNEXURES 84
PROFORMA
PLAGIARISM SCREENSHOT
PLAGIARISM CERTIFICATE
ETHICAL COMMITTEE APPROVAL CERTIFICATE
CONSENT FORM
MASTER CHART
INTRODUCTION
1
INTRODUCTION
Thyroid disorders constitute one of the most common endocrine disorders encountered in pregnancy as well as the reproductive life of a woman. It will be cheerful for every health personnel to conduct deliveries without any complications to both mother and the fetus at the end of the term gestation. There may be a hindrance for both the mother and the fetus if there is thyroid dysfunction.
Pregnancy is associated with significant alterations in the regulation of thyroid function. These alterations include an increase of thyroxine-binding globulin (TBG) due to elevated estrogen by decreasing the hepatic clearance of TBG, increased renal losses of iodine due to increased glomerular filtration rate, modifications in the peripheral metabolism of maternal thyroid hormones and modifications in the iodine transfer to the placenta.
The developing fetus relies on the mother for thyroid hormone synthesis in the early first trimester of pregnancy around 10-12 weeks. Foetal thyroid gland starts working by the end of the first trimester. Still, the foetus demands maternal iodine intake.
Thyroid hormones are crucial for neuronal development of the fetus. Thus, there is an elevated need for the maternal thyroid to meet these requirements. This can lead to either a physiologic goitrogenic effect in some pregnant women or can cause abnormality like hypothyroidism /hyperthyroidism.
2
Clinical hypothyroidism is associated with various pregnancy complications such as abortions, pre-eclampsia, anaemia, placental abnormalities and postpartum hemorrhage.
Also, the offspring of these mothers can have complications such as premature birth, low birth weight, IUGR and increased neonatal respiratory distress, congenital hypothyroidism and impaired cognitive function.
Iodine deficiency is attributed to be the commonest cause of hypothyroidism.
Hashimotos thyroiditis is the commonest cause in the developed countries. Normal development of placenta and the neuronal migration are dependent on thyroid hormones.
Auto immune thyroiditis commonly develops during the first postpartum year.
If we are able to identify such problems early in the pregnancy or just before conception, we will be able to prevent any adverse effects encountered in the mother and the fetus. It is also extremely important to titrate the dose of thyroid medications in a pregnant woman who is already a known case of hypothyroidism.
Interpretation of the TFT requires atmost attention because the cutoff values are not identical for both pregnant and the non-pregnant women. Also, the incidence of severe hypothyroidism in pregnancy is rare as most of them will not conceive.
Our study aimed to determine the prevalence of hypothyroidism in pregnancy and its association with various maternal and fetal outcomes in the population belonging to Central Chennai. We also would like to discuss regarding the recommendations of whether universal or high-risk screening to the populations.
AIMS AND OBJECTIVES
3
AIM AND OBJECTIVE OF THE STUDY
Aim:
1.To assess the prevalence of hypothyroidism in pregnant women.
2.To analyse the maternal & foetal outcome of pregnancies complicated by hypothyroidism.
Objective:
To determine whether Thyroid Function Test can be recommended as a universal screening or high-risk screening test for the pregnant mothers.
REVIEW OF LITERATURE
4
REVIEW OF LITERATURE
ANATOMY:
Thyroid gland is located anteriorly in the neck between the level of C5 vertebrae and T1 vertebrae and is rich in vascular supply. It is located deep in the platysma, sternothyroid and sternohyoid muscles, enveloped by the layers of deep cervical fascia.
The weight of the thyroid gland is approximately 15-20 gm. In newborn it is approximately 1gm.
The gland consists of two lobes (right and left) with pair of superior and inferior poles, and the lobes are connected together by isthmus. Each lobe measuring 4 cm in length, 2 cm in width and 2-3 cm in thickness. The isthmus measures 2 cm in width, 2 cm in height and 2-6 mm in thickness. 50 % of individuals present with a pyramidal lobe (also known as Morgagni’s or Lalouette’s pyramid).
5
The thyroid gland consists of a true inner capsule, which is firmly adherent to the gland.
The true capsule projects into the gland forming septae and divides into lobes and lobules.
There are also 2 pairs of parathyroid glands lying in close proximity to the gland tissue.
EMBRYOLOGY:
The first endocrine gland to develop in humans is the thyroid gland. A diverticulum located in the median ventral wall of the pharynx known as the thyroid diverticulum gives origin to the thyroid gland. During the 4th week of embryonal development, thyroid placode which is an endodermal thickening emerges in the floor of primitive pharynx between the first and second pharyngeal pouches. [1]
This primitive tissue which is hollow initially becomes solid and is called as the thyroid bud. It passes through the underlying mesenchymal tissue and reaches the lower neck by descending anteriorly through the thyroglossal duct and laryngeal cartilages.
The thyroid gland is more round in shape at first which then takes a bilobed structure as it enlarges towards the end of the 7th week of embryonal development and takes its final location in the neck in front of the trachea between 2nd and 5th tracheal ring.
6
During embryogenesis, the following transcription factors play a significant role in the development of thyroid gland. [2]
TTF-1 (thyroid transcription factor-1) PAX8 (paired box gene 8)
FOXE-1 (forkhead box E1)
HHEX (hematopietically expressed homeobox)
7
HISTOLOGY:
Thyroid gland when viewed microscopically, is divided into lobules. Each lobule consists of 20 to 40 round follicles, which form the main structural units of the thyroid gland. These follicles are lined by simple epithelium (single layer of cuboidal epithelium) which encloses a colloid filled cavity. The central colloid contains the main iodinated glycoprotein- known as the iodothyroglobulin. Thyroid is the only human gland in which hormonal product is stored extracellularly.
When the thyroid gland is stimulated, the follicular cells turn columnar and the lumen gets depleted of colloid.
When the thyroid gland function is suppressed, the follicular cells turn flat with the colloid getting accumulated inside the lumen.
There are also parafollicular cells which lie adjacent to the follicular cells within the basal lamina.
Epithelial cells of thyroid gland are of two types:
1. Principal cells (follicular cells)
2. Parafollicular cells (also known as C-cells)
8
The principal or follicular cells forms colloid, whereas the parafollicular cells (C- cells) form Calcitonin, the main hormone involved in calcium homeostasis of the human body.
9
PHYSIOLOGY OF THYROID GLAND :
Hormone synthesis in the thyrocyte can be grouped under three main steps:
1. Iodide uptake
2. Iodide oxidation & organification 3. Thyroid hormones secretion.
Step 1: Iodide Uptake:
Iodine is ingested with a number of food items including dairy products, grains, and meat. Fish, milk and eggs are rich sources of iodine. Approximately 150 µg of iodine is required by the thyroid gland for its daily activity. But in certain conditions like pregnancy and breastfeeding, the requirements are greater. [3] Upon ingestion, organic iodine is converted to inorganic iodide. Iodide is the chemical form that is needed for the biosynthesis of thyroid hormones. The thyroid and kidney are considered to be the most iodine-dependent organs. Thyroid stores nearly 90% of the body’s iodine. The excess iodine in plasma is excreted through kidneys.
The first step of Iodide trapping is an ATP dependent active transport across the basement membrane of the thyroid follicular cells (through Sodium/Iodide symporter). The thyroid follicular cells contain Thyroglobulin (Tg)- a glycoprotein with 4 tyrosyl residues.
10 Step 2: Iodide oxidation & Organification
The iodide which is now trapped in the cytoplasm of the polarized thyrocyte moves apically and gets oxidized, which is then covalently bound to thyroglobulin. This step is catalyzed by Thyroid peroxidase and requires H2O2. [6]
THYROID PEROXIDASE – It acts as an H2O2 DONOR & OXIDIZES IODIDE.
The resulting compounds maybe I+ or OI- (Hypoiodite). Both these compounds are capable of interacting with Thyroglobulin.
Iodination of Thyroglobulin results in,
MONOIODOTYROSINE (MIT)
DIIODOTYROSINE (DIT) COUPLING:
When a MIT is coupled to a DIT 3,5,3’-Triiodothyronine (T3) is generated.
When a DIT is coupled to another DIT 3,5,3’,5’-Tetraiodothyronine(T4) is generated. Also known as Thyroxine.
Noniodinated tyrosine donor couples to a DIT acceptor to form 3,5-diiodothyronine (T2).
Finally, 3,3’,5’-triiodothyronine (Reverse T3 or rT3) accounts for only 0.9% of thyroid hormones which is released in the circulation.
11
12
Step 3: Thyroid Hormones Secretion
:
In the final step, the peroxidase-processed thyroglobulin is endocytosed by follicularepithelial cells which fuses with lysosomes to form phagolysosomes. In these phagolysosomes hydrolysis of the thyroglobulin molecule takes place to release free iodothyronines (T4, T3) and mono and diiodotyrosines. The iodotyrosines which are released from the thyroglobulin are deiodinated by the help of Iodotyrosine deiodinase enzyme. Thus, most of the iodide is recycled for thyroid hormone synthesis again.
On stimulation of the thyroid gland, these formed thyroid hormones are released into the circulation. This peroxidase-processed thyroglobulin within the follicle act as a reservoir for thyroid hormones.
Regulation of Thyroid Hormones Biosynthesis:
Three important factors involved in the thyroid hormone biosynthesis and metabolism are:
• TSH-induced stimulation
• Availability of Iodine and
• Deiodinases enzyme activity.
TSH stimulate most if not all steps of thyroid hormones biosynthesis, from the uptake of iodine (by enhancing NIS expression) to internalization of Thyroglobulin
13
molecule from the follicular lumen and consequent secretion of thyroid hormones into the circulation. TSH is made and secreted by the thyrotropes present in the anterior pituitary gland.
TRH triggers TSH secretion, which is in turn synthesized by neurons of the paraventricular nucleus of the hypothalamus. In order to prevent hyperstimulation by TSH, and to restore the individual set point of the hypothalamus–pituitary–thyroid axis, there are multiple negative feedback loops.
The thyroid hormone itself inhibits both TRH and TSH secretion. TRH secreting neurons and tancytes are involved in the inhibition of TRH release. TSH regulates its own secretion by an ultra-short feedback loop maintained by thyrotropes.
The normal TSH physiological secretion is pulsatile and its secretion is 50 to 100 percent higher in the late evening than the daytime. The normal TSH secretion rate in individual ranges from 75 to 150mIU/day.
Availability of Iodine regulates the biosynthesis and secretion of thyroid hormones.
When iodine availability is insufficient, T3 and T4 are inadequately synthesized, TSH increases, and goitrogenesis occurs.
In addition, conversion of T4 to T3 is enhanced. In contrast, excessive iodine exposure leads to inhibition of thyroid hormones biosynthesis by blocking H2O2 production and Thyroglobulin iodination (The Wolff-Chaikoff effect).
14
Thyroid hormone activation and inactivation are regulated by the deiodinases.
Thyroid contains especially D1 and D2.
Type 2 deiodinase (D2) acts on the outer ring of T4, converting it into T3.
By contrast, Type 3 deiodinase (D3) inactivates T4 and T3, deiodinating their inner ring and converting them into rT3 and T2, respectively.
In addition, Type 1 deiodinase (D1) acts both on the outer and inner ring.
15
THYROID PHYSIOLOGY IN PREGNANCY:
As the pregnancy is associated with increased metabolic demand in the body and the developing fetus, it leads to major changes in the physiology of pituitary-thyroid axis and the iodine metabolism. This increased demand is met by elevation in thyroid function by 10% in iodine-replete areas. People living in iodine deficiency places, thyroid function increases by 20-40%. [4]
There is an increase in the production of thyroid hormones both T3 and T4 by 50%
in the first half of pregnancy, in association with 50% increase in daily iodine requirement.
It maintains a plateau range at around 20 weeks of pregnancy.
These changes in thyroid function during pregnancy are mainly due to the following reasons. [10,11]
Elevated maternal estrogen during pregnancy results in sialylation of the TBG and more production of TBG.
There is also decreased hepatic clearance of TBG resulting in pooling of TT3 and TT4 .
Serum βhCG has an activity similar to that of TSH as both of them have same a subunits and different b subunit. After fertilization βhCG escalates and reaches a maximum point at around 10 -12 weeks of pregnancy. So ft3 and ft4 levels increases in 1st trimester and TSH declines, followed by readoption of the same in the later trimester as βhCG declines.
16
The following flowchart helps us understand the mechanism involoved.
17
There is a transient resetting of the hypothalamic-pituitary-thyroid axis negative feedback mechanism in early gestation aimed at increasing T4 supply to the fetus. Fetal development requires the maternal T4 supply when the fetal thyroid gland is not yet ready to secrete the hormone.
The production of 17B estradiol and epidermal growth factor in human placenta is triggered by T3. This increased supply of thyroid hormone has a significant role at this crucial stage of trophoblast invasion, placental tissue differentiation and development. [7]
18
REFERENCE VALUE FOR TSH IN PREGNANCY
TSH levels during pregnancy are not the same as seen in the non-pregnant state.
They are at a much lower level because of the significant physiological changes in the size and action of the thyroid gland that occurs during pregnancy.
Pregnancy-specific and trimester-specific reference values for TSH are as seen below:
[12]
TRIMESTER VALUE
1
sttrimester 0.1-2.5mIU/l
2
ndtrimester 0.2-3mIU/l
3
rdtrimester 0.3-3mIU/l
However, some recent studies conducted in Asian countries shows only a slight decrease in the upper refence limit. Looking at the body of evidence, the upper reference range should be set at 4.0 for the late first trimester (7-12 weeks) with return to non-pregnant range in the 2nd & 3rd trimesters. [5]
Trimester fT3 (pg/mL) fT4 (ng/dL)
1
sttrimester 2.11-3.83 0.70 -2.00
2
ndtrimester 1.96-3.38 0.50 -1.60
3
rdtrimester 1.96-3.38 0.50 -1.60
19
IODINE IN PREGNANCY:
Thyroid hormone production is solely dependent on iodine. 52 µcg of iodide is needed everyday by the thyroid gland to synthesize the required amount of thyroxine.
Iodine rich foods are fish, seafood, kelp, some drinking water and vegetables cultivated in iodine rich soil. Cow’s milk is a rich source of iodine.
During pregnancy, there is an increase in iodine demand by about 50% due to multiple factors. There is also an increase in urinary iodine excretion because of elevated glomerular filtration rate and elevated plasma clearance of iodine. [4]
Women residing in iodine sufficient areas with good stores are able to meet this demand. Women living in the iodine-deficient areas, there is a drop in thyroid hormones levels leading to increased TSH production and thereby hypothyroidism.
Adequate iodine is needed for the neurological maturation of the fetus which occurs soon after the women conceives. Degree of iodine deficiency correlates with the abnormalities that occur in the neonates.
Severe Iodine deficiency can result in pregnancy losses, stillbirth, perinatal and infant mortality rates. It can affect the transfer of maternal thyroid hormones via the placenta to the fetus and can cause cognitive impairment in the offspring and results in development of cretinism in them.
20
So higher dietary intake of Iodine is recommended in pregnancy compared to the non-pregnant state. WHO recommends total daily iodine intake of 250 µg per day for the pregnant and lactating women. [4]
The total iodine intake must not exceed 500µg/day because some individuals may not be able to escape the wolff-chaikoff effect and become susceptible to hypothyroidism in the light of elevated iodine levels.
Iodine status of a woman can be assessed by the urinary iodine levels. [13]
Median urinary iodine concentration Iodine
sufficiency
Children
Nonpregnant adults
100-299 µg/l
Pregnant woman 150-249 µg/l Iodine
deficiency
Mild 50-149 µg/l
Moderate 20-49 µg/l
Severe <20 µg/l
Associated iron deficiency, selenium deficiency, and vitamin A deficiency can also aggravate the outcomes of iodine deficiency.
21
HYPOTHYROIDISM
This is a condition occurring as a result of underactive thyroid glands that secretes inadequate levels of thyroid hormones. Hypothyroidism is seen in both the sexes, but is more common in females.
PRIMARY MATERNAL HYPOTHYROIDISM
This is a condition characterized by the presence of increased TSH levels during pregnancy.
Primary hypothyroidism is further classified as subclinical and overt hypothyroidism.
Subclinical hypothyroidism is described as pregnant women with TSH value between 2.5 to 10 mIU/l (1st trimester) and 3 to 10 mIU/l (2nd &3rd trimester) with free T4 levels in a normal range. It is more common and is frequently reported thyroid disorder in pregnancy. [8]
Overt hyperthyroidism is described as the pregnant women with abnormally high TSH value with abnormally low total /free T4 levels. It can also be described as a TSH value more than 10 mIU/l irrespective of free T4 values. [8]
22
CAUSES OF HYPOTHYROIDISM [7]
Autoimmune Hashimoto’s (chronic)
De Quervain’s thyroiditis (subacute, transient)
Iatrogenic Surgical removal of thyroid (thyroidectomy)
Previous Radioactive iodine treatment Drug-induced (e.g. lithium, amiodarone) Congenital
hypothyroidism
Thyroid gland agenesis Thyroid dyshormonogenesis
Genetic mutations of thyroid d receptors
Substance deficiency Iodine deficiency (the commonest cause)
Infiltrative disorders Sarcoidosis
23
Clinical presentation of hypothyroidism:
The patients usually present with insidious nonspecific symptoms like fatigue, constipation, cold intolerance, muscle cramps and unusual weight gain. Unusual signs and symptoms like edema, dry skin, hair loss, slow pulse rate and prolonged relaxation phase of deep tendon reflexes have also been reported.
If the patient presents with myxedema which is a very rare condition, she may have typical facial features with yellowish skin, brittle hair and significant loss of outer two third of the eye brow. Inadequately treated patients can develop myxedema madness.
Women with Hashimoto's thyroiditis or those living in iodine-deficient areas can present with enlarged thyroid gland.
Menstrual abnormalities like oligomenorrhoea, amenorrhea, polymenorrhoea and menorrhagia have been noted in these women.
These symptoms are commonly seen in overt hypothyroidism. Women with subclinical hypothyroidism are usually asymptomatic and are diagnosed on their routine antenatal workup.
24
PREVALENCE OF HYPOTHYROIDISM:
Globally, the prevalence of hypothyroidism is estimated to be around 2-3%. Around 0.3 to1.2% are overt hypothyroid and 0.2-2.5% are subclinical hypothyroid.
Among the Indian population, a much higher prevalence of hypothyroidism has been reported ranging from 4.8%-11%. [15]
The prevalence varies widely between the Asian and Western countries. Similarly, variations have been reported with in India with higher prevalence in northern states.
Reason could be due to the geo-chemical nature of iodine deficiency due to glaciations, high rain falls and floods mounting to decreased iodine content in the soil and the water.
In a study conducted by Gupta et al (2017), he reported prevalence of hypothyroidism to be 6.22%. Of which, 3.77% were subclinical hypothyroid and 2.45
%were overt hypothyroid. [16]
Ajmani et el (2014) in his study mentioned that 12% were hypothyroid. Among them, 9% were subclinical hypothyroid and 3 % were overt hypothyroid. [14]
Nambiar et al (2015) reported a prevalence of 4.8% of hypothyroidism and 12.4%
of thyroid autoimmunity in his research. [15]
25
EFFECTS OF HYPOTHYROIDISM ON PREGNANCY:
Uncorrected hypothyroidism has several adverse effects on the mother as well as the fetus. Women being hypothyroid at the early weeks of pregnancy are at increased risk of developing the complications when compared to being euthyroid.
Newly diagnosed hypothyroid during pregnancy were treated, if they become euthyroid before 20 weeks, overall complication rate was 4.8%; If they become euthyroid after 20 weeks, it was 19% and who never achieved euthyroid level during pregnancy, it was 31.5% [4]
Continuation of pregnancy with uncorrected hypothyroidism can result in any of the following illustrated complications:
MATERNAL COMPLICATION
Preeclampsia, Eclampsia,GHT
Placental Abruption
Postpartum Haemorrhage Anaemia
Preterm Labour
Oligohydromnios
26
Though overt hypothyroidism is associated with anovulatory cycles and are associated with infertility and increased first trimester abortions, they are associated with the above- mentioned complications at an increased rate when compared to subclinical hypothyroid patients. [18]
Some studies suggest that women with subclinical hypothyroidism reported a higher incidence of severe preeclampsia, preterm delivery, placental abruption, and/or pregnancy loss as compared with the euthyroid women. Some studies demonstrate significant association between subclinical hypothyroidism and impaired cognitive development in the offspring.
FETAL COMPLICATIONS Low Birth
Weight IUGR
Perinatal Mortality And
Morbidity
Neuropsuchological and Cognitive Imapirment of
the child
27
HYPOTHYROISIM AND ANAEMIA
Anemia is defined as hemoglobin concentration that is lower than the threshold of two standard deviation resulting in the decreased oxygen carrying capacity of the blood.
Hb < 11g/dl is considered as anemia according to WHO. CDC has the cutoff value of
<10.5g/dl in the second trimester.
Red cell abnormalities are commonly encountered in thyroid disorders. Thyroid hormones often have influence on erythropoiesis. [19,20,21]
THYROID HORMONES
hyper proliferation of immature
erythroid progenitors
augment repletion of
hypoxia inducible factor1 (HIF-
1
)intensify erythrocyte 2, 3
compactnessto DPG enhances the delivery of oxygen
to tissues
motivate growth of erythroid colonies (BFU-E,
CFU-E).
increase secretion of
EPO by inducing erythropoietin
gene
expression.
28
Different forms of anemia (normochromic-normocytic, hypochromic-microcytic or macrocytic) are caused by hypothyroidism via reduction the oxygen metabolism.
Thyrotrophic response to TRH, serum T3 and T4 levels are reduced in iron deficiency. This decreases the turnover of T3 and also T3 nuclear binding.
Hypothyroidism causes bone marrow repression and also lack of erythropoietin production occurring from the reduction in the need of O2 results in the development of microcytic, hypochromic anaemia.
Hypothyroidism also causes B12 deficiency through absorption problem due to decreased intestinal motility, edema of the intestinal wall and bacterial infiltration [22].
Hypothyroidism also results in folate deficiency by disrupting the folate mechanism via reduction in the hepatic levels of dihydrofolate reductase such as methylene- tetrahydrofolate reductase [23].
29
HYPOTHYROIDISM AND PREECLAMPSIA
Gestational hypertension is labelled as new onset hypertension occurring after 20 weeks of gestation without proteinuria or any other systemic features of preeclampsia in a previously normotensive women that resolves within 3 months postpartum.
Preeclampsia is defined as hypertension associated with proteinuria after 20 weeks of gestation.
Eclampsia is nothing but convulsions occurring in a patient with preeclampsia. Any seizure of unknown origin during pregnancy should be attributed as eclampsia unless otherwise proven.
Hypothyroidism causes reduction in the production of nitric oxide and cause impairment in the vascular relaxation there by leading to endothelial dysfunction.
Endothelial dysfunction is the major pathogenic event involved in the development of preeclampsia.
30
HYPOTHYROIDISM AND IUGR
Fetal growth restriction is considered as a pathological condition where the fetus has not attained its genetic growth potential, irrespective of the fetal size.
This accounts for the second primary cause of perinatal mortality, causing nearly 30% of stillbirth.
Endocrine paracrine and autocrine events along with fetoplacental unit are responsible for fetal development and growth. Any defect of this unit can lead to IUGR which can be symmetrical or asymmetrical.
There is a strong association between thyroid levels and fetal hypoxia. Oxygen usage is decreased in the peripheral tissues because of the low thyroid hormone levels. This leads to destruction in the neurodevelopment as peripheral tissues will not able to maintain the viability. There is also a poor expression of thyroid receptor isoforms in the cerebellum and cortex of such fetus.
31
THYROID HORMONE AND THE FETUS [7]
By around 12 weeks of gestation, there is a completion in the embryogenesis of the fetal thyroid gland and there is an accumulation of iodide and production of thyroid hormone. Fetal hypothalamus demonstrates TRH and Fetal TSH is also detected in the anterior pituitary at this age. The thyroid hormones T3, T4 are released into the circulation in measurable amounts from 16-18 weeks onwards.
Thyroid hormone synthesis by negative feedback mechanism emerges by approximately mid-gestation (20 weeks). There is a constant and progressive rise in TSH, total T4, and TBG levels as the gestation advances.
Maternal thyroid hormone is substantially at higher levels than the fetal thyroid hormones but this variation gets altered as the pregnancy advances. There is an elevation of both thyroid hormones and TBG in the fetus near term. Similarly, fT3 increase only in late pregnancy and fT4 reaches adult levels by 36 weeks.
The fetal thyroid gland has not matured completely up to 36-40 weeks of gestation in its ability to adapt to exogenous iodine. Hence preterm babies are more susceptible to thyroid suppressing effects of exogenous iodine than the term babies.
The major fetal thyroid hormone is T4 and the level of T3 is quite low throughout the pregnancy. rT3 levels parallelly elevates with the rise of T4. Thus, the fetus goes from a state of relative T3 deficiency to T3 thyrotoxicosis during delivery.
32
Placenta is freely permeable to TRH but not to TSH. Maternally obtained TRH plays a role in regulates the fetal thyroid function.
Following delivery with 30 mins,
TSH surge occurs reaching a peak of 80mU/L at 6 hours which then falls rapidly over 24 hours and then a much lower decline over the first 7 days of life.
There is also an activation of the maternal thyroid gland which results in the elevated production of serum T3 and T4 levels.
33
Thyroid hormone dependent neuro development involves 3stages:
Fetal brain development depends partly on the maternal and partly on the fetal thyroid status in utero. Even though some degree of corrections occurs if either one is lacking, there is demonstrable variation in the neuropsychological development compared to euthyroid.
Some expert argues that neurocognitive dysfunction of the children of women with subclinical hypothyroidism could be due to preterm delivery. (49)
first stage
-
occurs before the onset of fetal thyroid hormone synthesis.
-influences
neurogenesis and neuronal migration.
-areas involved are cerebral cortex, hippocampus and medial ganglionic eminence.
second stage -occurs during the rest of the
pregnancy.
-causes axon and dendrite -migration, glail cell proliferation and myelination.
3rd stage
-occurs in postnatal period.
-specific cell types are formed in the
cerebellum
,hippocampusand cortex.
-hormone dependent gliogenesis and
myelination occurs
.34
AUTOIMMUNE THYRODITIS
It is a chronic condition commonly encountered in the females of 30 -50 years of age. This may account for thyroid dysfunction in nearly 10% of the population. It includes a spectrum of disease ranging from Hashimoto's thyroiditis (HT) or chronic autoimmune thyroiditis and its variants, Graves' disease (GD), postpartum thyroiditis and autoimmune atrophic thyroiditis or primary myxedema. [4]
It is an autoimmune condition characterized by the development of antibodies against the three major thyroid antigens namely
1. Thyroid peroxidase 2. TSH receptor 3. Thyroglobulin
Various genetic and environmental factors contribute to the development of autoimmunity which includes HLA-DR genotype, T-cell defects, iodine, viral infection and oxidative stress. Clinically it can present as either atrophic thyroiditis or goitrous thyroiditis.
There is an extensive lymphocytic infiltration with development of germinal centre and eradication of follicular cells in Hashimotos variety. Graves’ disease shows hypertrophic and hyperplastic thyroid follicles with columnar epithelium and decrease in the colloid size.
35
Effect of autoimmune thyroiditis
Autoimmune thyroid disease is associated with increased risk of miscarriage, preterm delivery, perinatal death, postpartum thyroid dysfunction and decreased motor and intellectual development in the offspring. [4]
Thangaratinam et al demonstrated a substantiate risk for unexplained subfertility, abortions, recurrent pregnancy loss, preterm delivery and postpartum thyroiditis in euthyroid pregnant women who showed the presence of various thyroid antibodies. [37]
There are also studies which show some association between the TPO antibodies and depression, postpartum mood disturbances and anger irrespective of having postpartum thyroiditis.
Nambiar et al in his study stated higher prevalence of thyroid autoimmunity being 12.4%. He reported 3 times higher rate of miscarriage when compared to other studies. The possible explanation could be due to rejection of the fetal graft as thyroid autoimmunity is considered as a marker of generalized immune imbalance. He also reported a higher incidence of history of still births in women with thyroid autoimmunity.[15]
There is no clear-cut treatment protocol is available for the pregnant mothers identified with thyroid antibodies. Hence serial monitoring of the serum TSH should be done to detect the development of hypothyroidism in future.
36
TPO ANTIBODIES:
It is imperative to assess the thyroid antibody status in pregnant women. Thus, while doing TFT, it is advisable to do TPO antibodies.
Negro et al demonstrated a higher risk of adverse pregnancy outcomes at a lower TSH level in women with subclinical hypothyroidism and positive anti-thyroid peroxidase (TPO)antibodies than in women with negative TPO antibodies. [38]
Similarly, higher incidence of foetal loss, perinatal mortality and large for gestational age babies was reported in euthyroid women with high TPO antibody concentrations in another study. Increased incidence of subclinical hypothyroidism in first trimester and thyroiditis in the postpartum period were reported in these pregnant women.
According to ATA, TPO-positive women at a TSH level >2.5 mIU/L revealed a higher risk of pregnancy-specific complications which was not seen in TPO-negative women until TSH values exceeded 5 to 10 mIU/L.
There is still a debate on whether to monitor the euthyroid women with positive TPO antibodies or to treat them with levothyroxine. Some studies demonstrated a decrease in the incidence of abortions after treatment with levothyroxine. But still, large trails need to done to build a standard guideline for the same. [4]
37
POSTPARTUM THYROIDITIS [5,7]
It is an autoimmune inflammatory disorder with its recognition during the first year of the childbirth. Worldwide prevalence is around 5% which may be up to 25% in women with type 1 diabetes mellitus. Postpartum thyroiditis has a positive correlation with anti- TPO antibodies.
Transient subacute destructive lymphocytic infiltration is the histologic picture seen in this condition. FNAC depicts lymphocytes, thyroid follicular cells and masses of colloid.
It has a biphasic pattern of hyperthyroidism followed by hypothyroidism in 90 percent of the patients. It can also be present as either hypothyroidism only or hyperthyroidism only.
Etiology:
1.Postpartum rebound in the maternal immune system.
2. Brief elevation in the antithyroid antibodies.
3. Increased NK cell activity and complement activation.
Clinical manifestation:
It is a painless condition usually asymptomatic but can also be mildly symptomatic during the hyperthyroid stage. It can also be present with other features of hyperthyroidism like irritability, heating intolerance, fatigue and palpitation. Hypothyroid exhibits
38
symptoms like cold intolerance, dry skin, fatigue, impaired concentration and paresthesia.
Some studies reported an association between PPT and postpartum depression.
Diagnosis: biochemical evaluation.
Treatment
Most of the affected women doesn’t need treatment during the either phase of the disease, but needs cautious monitoring of the thyroid function.
Thyrotoxic phase
This phase will not respond to antithyroid drugs because it is a destructive disorder where hormone production cannot be increased. Beta blockers can offer symptomatic relief to the patients and also it is safe during breastfeeding.
Drugs: Propranolol, metoprolol Hypothyroid phase
Treatment with thyroxine should be offered to the women for 6 to 12 months followed by gradual tapering with the monitoring of TSH every 6-8 weeks.
Recurrence in subsequent pregnancy is reported to be around 70 %. These patients have to followed up with yearly TFT as 25% of them are at risk of developing permanent hypothyroidism in the next 5 years.
39
SCREENING OF HYPOTHYROIDISM
From the recognition of adverse effects of hypothyroidism on mother and the foetus, there has been an argument on whether to have universal screening or targeted screening.
The latter is favored because of low cost, practicality and failure of any research to prove that universal screening is better over target screening.
Screening is a method of detection of the presence of unrecognized disease in an asymptomatic people by application of tests or procedures.
To recommend universal screening for a disease, 1. The disease must have a high incidence 2. The screening test must be cost effective.
3. Early detection and treatment should reduce the morbidity.
Universal screening includes screening of a whole population or a subgroup whereas targeted screening is selectively applied to a high-risk group.
Vaidya et al., in his study stated that universal screening is superior to screening only high-risk women because high-risk screening has missed 30% of women with hypothyroidism. [24]
Negro et al., also figured out the same which states that adverse pregnancy outcomes were less following treatment in those women identified by universal screening vs. targeted case finding for thyroid dysfunction in pregnancy.[25]
40
The Endocrine Society (2012) does not recommend universal screening of all pregnant woman but encourages TSH in “high risk” individuals.
Guidelines from the AACE and the American Thyroid Association (2012) do not recommend universal screening but only women at risk. The Society of Maternal Foetal Medicine published the same recommendations in 2012. [26]
Furthermore, the American College of Obstetricians and Gynaecologists (ACOG) in 2015 recommended “thyroid testing in pregnant women only if they were symptomatic, or had a personal history of thyroid disease or other medical disorders such as Diabetes Mellitus”. [27]
Comments of Cochrane collaboration in 2010 that “until more convincing data becomes available, only pregnant women at risk for thyroid disease should be tested”. [28]
World Health Organization (WHO) has not given any recommendation regarding thyroid screening in pregnancy.
Recommendation of Indian Thyroid Society (ITS) is that “screening of TSH levels in all pregnant woman at the time of their first visit, ideally during prepregnancy evaluation or as soon as pregnancy is confirmed”.
Recent “2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during Pregnancy and the Postpartum” states [5]:
The role of Universally screening of thyroid dysfunction during pregnancy remains controversial at present.
41
There is still insufficient data to recommend for or against universal screening for TSH in early pregnancy.
Any screening for detecting low fT4 concentrations in pregnant women is not recommended.
It strongly recommends that all pregnant women be verbally screened at the initial prenatal visit for any history of thyroid dysfunction, and prior or current use of either thyroid hormone or antithyroid medications.
If pregnant women have any of the following risk factors, then testing for serum TSH is recommended: [5]
1. A history suggestive of hypothyroidism/hyperthyroidism or current symptoms/signs of thyroid dysfunction.
2. Previous known thyroid antibody positivity or goitre present.
3. Any prior history of head or neck radiation or thyroid surgery 4. Age >30 years
5. Type 1 diabetes or autoimmune disorders
6. Past history of pregnancy loss, preterm delivery, or infertility 7. Multiple prior pregnancies (≥2)
8. History of autoimmune thyroid disease or thyroid dysfunction in the family members.
42 9. Morbid obesity (BMI ≥40 kg/m2)
10. Intake of amiodarone or lithium, or recent administration of iodinated radiologic contrast.
11. Resident of area with moderate to severe iodine deficiency.
12. History of diagnosed mental retardation in family/previous births.
MANAGEMENT OF HYPOTHYROIDISM
The one and only drug used in treating hypothyroidism is levothyroxine.
This levo-isomer of thyroxine is a synthetic preparation. It has a bioavailability of 48%to 80% with a considerable amount being absorbed from jejunum and ileum. Route of excretion is by the kidneys. Fasting state increases its absorption. Calcium and iron should be preferably avoided for 4 hours pf taking this medication.
It is prescribed in oral formulations as levothyroxine sodium. 25 µg, 50 µg and 100 µg are the various strength available. Room temperature is ideal for its storage. Patient should be informed not expose the medicine to the direct sunlight always.
43
The patient has to take this medicine per orally in empty stomach in the morning.
The patient is informed not to take anything for the next half an hour after its intake orally.
FDA approve this drug under category A and can be used safely during pregnancy and lactation and has no adverse effects on the mother and the foetus.
If the patient fails to take the tablets on one day, then she must be advised to take it as early as possible when she remembers and inform her not to take anything orally for the next half an hour.
If the patient fails to take the tablet one whole day, recommendation is to take twice the dose in the next morning. There are no reported contraindications to this medicine. The dose that we recommend for treatment has no proven side effects.
Researches have shown that initiation of treatment of hypothyroidism preconceptionally or early in the first trimester has reduced the incidence of adverse maternal and fetal outcomes. Thus attainment of trimester specific TSH level should be the target of our treatment.
Dr. Abalovich and colleagues addresses "initiation of treatment in newly diagnosed hypothyroidism following levothyroxine doses: [17]
Type Level dose
Subclinical hypothyroidism TSH <4.2 1.20 µg/kg/day Subclinical hypothyroidism 4.2-10 1.42 µg/kg/day Overt hypothyroidism >10 2.33 µg/kg/day
44
TSH levels need to be monitored every 6 after starting the medication.
Dose adjustment based on TSH values: [12]
Overcorrection should also be avoided as it can iatrogenically convert the patient to hyperthyroidism. When TSH <0.1mIU/l, decrease the dose as follow:
45
National guidelines for screening of hypothyroidism during pregnancy has recommended the following for the treatment of hypothyroidism [12].
MATERIALS AND METHODS
46
MATERIALS AND METHODS
Study design:
An analytical cross-sectional study with internal comparison.
Study period:
September 2017 to July 2018 Place of Study:
Antenatal OPD and Labor Ward Casualty in the Department of Obstetrics &
Gynecology, Govt Kilpauk Medical College & Hospital, Chennai.
Inclusion criteria:
1.All women with singleton pregnancy in third trimester.
2.Known hypothyroid prior to pregnancy or newly diagnosed hypothyroid during pregnancy
3.Willing to deliver in our hospital
Exclusion Criteria:
Women with 1. Multiple Gestation
2.Chronic Hypertension.
47 3.Overt diabetes mellitus
4. Any autoimmune disorders
5.Those who are not willing to deliver in our hospital Study Setting:
Study involved screening 932 antenatal eligible women belonging to third trimester after obtaining the consent.
The research proposal was presented before the Institutional Review Board of Government Kilpauk Medical College and Hospital, Chennai and approved prior to the recruitment of cases.
Sample Size
The confidence level is estimated at 95% with a z value of 1.96 The confidence interval or margin of error is estimated at +/-12 Assuming p% =2.1 and q%=97.9
n = p% x q% x [z/e%] ² n= 2.1x 97.9 x [1.96/3]² n= 87.75 (rounded up to 88)
With Attrition 10% = 88+9=97
Therefore 97 is the minimum sample size required for the study assuming 80% as the power of study.
48
Blood was collected in fasting state from the patients by venu puncture (2ml), allowed to clot, and serum was separated by centrifugation at room temperature. The serum was stored at 2 to 8°C till its usage.
The TSH was measured by ELISA method. Abnormal serum TSH required estimation of fT3 and fT4.
TSH ESTIMATION in laboratory:
Method
Solid Phase Two-Site Immuno Radio Metric Assay (IRMA) with IRMAK-9 kit, BRIT, Mumbai.
Principle
In IRMA, two antibodies generated against different portions (epitopes) of the same antigen are used. One of the antibodies is bound to a solid phase, while the other is labeled with 125I. Thus, the antigen binds both antibodies in a “sandwich” fashion. The radioactivity in the bound fraction is quantitated using a gamma counter
Reagents
hTSH monoclonal antibody coated tubes 125I- Anti hTSH Wash diluents.
Specimen collection
Serum or plasma can be used for assay. EDTA plasma is not used.
49 FREE T3 & FREE T4 ESTIMATION
Method
RIA (Radio Immuno Assay) – IMMUNOTECH Prague, Cze ch republic Principle
The radio immuno assay of the free tri-iodo thyronine (T3) is a competitive assay done by using labeled antibody. Samples and calibrators are incubated with an 125I- labelled antibody specific for T3, as tracer, in tubes coated with an analog of T3 (ligand).
The free tri-iodo thyronine and the ligand compete for the binding to the labeled antibody.
The content in the tubes is aspirated after incubation and bound radioactivity is measured. A calibration curve is designed and values are ascertained by interpolation from the curve.
Reagents
Ligand-coated tubes 125I- labeled monoclonal antibody Calibrators Control serum.
Based on these values and the previous history, participants were grouped into subclinical and overt hypothyroidism.
The patients were treated with L-thyroxine as per the National guidelines for screening of hypothyroidism during pregnancy
50
The women were followed every 6 weeks with TSH, till delivery and the details were recorded regarding the complications and the mode of delivery. Target TSH level should be < 3m IU/L in the third trimesters.
The new born baby details were also obtained from the neonatologist at the time of delivery. These women after delivery in post-partum period were suggested to start pre- pregnancy dose of Levothyroxine or the same dose depending on the time of onset of the disease and advised to review in Endocrinology department with serum TSH levels after 4-6 weeks.
DATA ANALYSIS
Descriptive statistics was done for all data and were described in terms of mean values and percentages. Suitable statistical tests of comparison were done. Continuous variables were evaluated using unpaired t test. Categorical variables were evaluated with the Chi-Square Test and Fisher Exact Test. Statistical significance was taken as P < 0.05.
The data was analysed using SPSS version 16 and Microsoft Excel 2007.
OBSERVATION AND ANALYSIS
51
OBSERVATION AND ANALYSIS PREVALENCE OF HYPOTHYROIDISM
Prevalence of Hypothyroidism Number %
Euthyroid
834 89.48
Subclinical Hypothyroidism
61 6.55
Overt Hypothyroidism
37 3.97
Total
932 100
Out of 932 pregnant antenatal mothers screened,98 were found to be hypothyroid. The prevalence is found to be 10.5%
They were grouped into subclinical and overt hypothyroid based on the ft4 values. The prevalence of subclinical hypothyroidism is 6.55% and overt hypothyroidism is 3.975% in our study.
834
61 37
89.48
6.55 3.97
0 100 200 300 400 500 600 700 800 900
Euthyroid Subclinical Hypothyroidism Overt Hypothyroidism
Number of Subjects
Prevalence of Hypothyroidism
Number %
52
STUDY GROUPS
Study Groups Intervention Number %
Subclinical Group
Upper value of TSH level > 3 mIU/L and free T4 is
normal 61 62.24
Overt Group
Upper value of TSH level > 3 mIU/L and free T4 is below normal
37 37.76
Total 98 100.00
61
37
98
62.24
37.76
100.00
0 20 40 60 80 100 120
Subclinical Overt Total
Number of Subjects
Study Groups For Internal Comparisions
Number Percentage
53
AGE DISTRIBUTION
Age Groups Subclinical % Overt % Total %
≤ 20 years 4 6.56 2 5.41 6 6.12
21-25 years 30 49.18 22 59.46 52 53.06
26-30 years 21 34.43 9 24.32 30 30.61
> 30 years 6 9.84 4 10.81 10 10.20
Total 61 100.00 37 100.00 98 100.00
Age Distribution Subclinical Overt Total
Mean 25.28 24.92 25.14
SD 3.19 3.20 3.18
P value
Unpaired t Test 0.590
Most of the subclinical group subjects were in 21-25 years age group (49.18%) with a mean age of 25.28 years. In overt group, majority too were in 21-25 years age group (59.46%) with a mean age of 24.92 years. (p= 0.590). The data subjected to unpaired t test reveals the existence of statistically non-significant association between age distribution and study groups (p > 0.05)
4 2 6
30
22
52
21
9
30
6 4
10 0
10 20 30 40 50 60
Subclinical Overt Total
Number of Subjects
Age Groups
≤ 20 years 21-25 years 26-30 years > 30 years
54
GESTATIONAL AGE
Gestational
Age Subclinical % Overt % Total %
28 weeks 19 31.15 9 24.32 28 28.57
29 weeks 12 19.67 11 29.73 23 23.47
30 weeks 15 24.59 9 24.32 24 24.49
31 weeks 15 24.59 8 21.62 23 23.47
Total 61 100.00 37 100.00 98 100.00
P value Chi squared
Test 0.932
Most of the subclinical group subjects were around 28weeks of gestation (31.15%) and most of the overt group subjects were 29 weeks of gestation (29.73%) (p= 0.0932). The data subjected to chi squared test reveals the existence of statistically non-significant association (p >0.05)
19
9
28
12 11
23
15
9
24
15
8
23
0 5 10 15 20 25 30
Subclinical Overt Total
Number of Subjects
Gestational Age
28weeks 29 weeks 30 weeks 31 weeks
55
OBSTETRICS SCORE
Obstetric
Score Status Subclinical % Overt % Total %
Primi Gravida 27 44.26 15 40.54 42 42.86
Second
Gravida 19 31.15 15 40.54 34 34.69
Third Gravida 15 24.59 7 18.92 22 22.45
Total 61 100.00 37 100.00 98 100.00
P value Chi squared
Test 0.610
Most of the subclinical group subjects were primi gravida (44.26%) and in overt group majority were equally distributed in primi and second gravida (40.54%) (p= 0.610). There was a statistically non-significant association between obstetric score status and study groups (p >0.05)
27
15
42
19
15
34
15
7
22
0 5 10 15 20 25 30 35 40 45
Subclinical Overt Total
Number of Subjects
Obstetric Score Status
Primi Gravida Second Gravida Third Gravida
56
ANAEMIA
Anaemia
Status Subclinical % Overt % Total %
No 52 85.25 24 64.86 76 77.55
Yes 9 14.75 13 35.14 22 22.45
Total 61 100.00 37 100.00 98 100.00
P value Chi squared
Test 0.019
The prevalence of anaemia was 35% in the overt hypothyroid and 15% in the subclinical hypothyroid group (p= 0.019). This reveals the existence of statistically significant association between anaemia status and study groups (p <0.05)
52
24
76
9 13
22
0 10 20 30 40 50 60 70 80
Subclinical Overt Total
Number of Subjects
Anaemia Status
No Yes
57
PREECLAPMSIA
Pre- Eclampsia
Status Subclinical % Overt % Total %
No 51 83.61 19 51.35 70 71.43
Yes 10 16.39 18 48.65 28 28.57
Total 61 100.00 37 100.00 98 100.00
P value Chi squared
Test <0.001
Preeclampsia is reported in 49% of the overt hypothyroid and 16% of the subclinical hypothyroid group (p= <0.001) which shows a statistically significant association.
51
19
70
10
18
28
0 10 20 30 40 50 60 70 80
Subclinical Overt Total
Number of Subjects
Pre Eclampsia Status
No Yes
