|Year : 2017 | Volume
| Issue : 1 | Page : 81-84
Thyroid dysfunction in early pregnancy and spontaneous abortion
Preeti Gahlawat1, Aditi Singh2, Smiti Nanda1, Simmi Kharb2
1 Department of Biochemistry, Obstetrics and Gynecology, Pt. B.D. Sharma PGIMS, Rohtak, Haryana, India
2 Department of Biochemistry, Pt. B.D. Sharma University of Health Sciences, Rohtak, Haryana, India
|Date of Web Publication||24-Jul-2017|
#1396, Sector.1, Rohtak, Haryana
Source of Support: None, Conflict of Interest: None
Background: Pregnancy is associated with significant but reversible changes in thyroid function. Abnormal thyroid hormone levels could give rise to increased malplacentation increase to malplacentation that underlies the association between maternal thyroid dysfunction and adverse obstetric outcomes such as fetal brain damage, preterm births, and fetal death. Aim: The present study was planned to predict the risk of abortion in pregnancy by studying the relation between thyroid profile and rate of abortion. Methods: This prospective observational study was carried out in 100 pregnant women with a singleton pregnancy of 6–12 weeks of gestation in the Department of Biochemistry in collaboration with the Department of Obstetrics and Gynaecology, Pt. B.D. Sharma, PGIMS, Rohtak. The patients were divided into three groups, namely, Group 1 (n = 30, control group) included normal pregnant women with no history of abortion; Group 2 (n = 35) included pregnant females with previous history of abortion; and Group 3 (n = 35) comprised pregnant women coming with chief complaint of bleeding per vaginum. A volume of 5 mL blood sample was taken and serum was separated using centrifugation. Triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) levels were estimated by chemiluminiscence. Results: T3, T4 and levels were comparable in all the three groups and the difference was not statistically significant. TSH levels were found to be negatively correlated with T3 and T4 values in the three groups. Only, 13% of the patients had spontaneous abortion. Nearly 6.66% of the patients in Group 1, 11.42% in Group 2 and 19.99% of patients in Group 3 ended up in abortion. TSH was found to be strongly associated with abortion in all the three groups (P ≤ 0.001). TSH levels were significantly higher in the first trimester in women who had an abortion than pregnant women who had a successful continuation of pregnancy. Conclusions: TSH was strongly associated with abortion in the first trimester in all the three groups.
Keywords: Abortion, gestational age, pregnancy, thyroid
|How to cite this article:|
Gahlawat P, Singh A, Nanda S, Kharb S. Thyroid dysfunction in early pregnancy and spontaneous abortion. Biomed Biotechnol Res J 2017;1:81-4
|How to cite this URL:|
Gahlawat P, Singh A, Nanda S, Kharb S. Thyroid dysfunction in early pregnancy and spontaneous abortion. Biomed Biotechnol Res J [serial online] 2017 [cited 2019 Jun 26];1:81-4. Available from: http://www.bmbtrj.org/text.asp?2017/1/1/81/211410
| Introduction|| |
Spontaneous abortion is the most common complication of early pregnancy and more than 80% of the spontaneous abortions occur within the first 12 weeks of gestation. The main causes leading to abortion could be either fetal or parental. Fetal factors can be chromosomal anomalies (such as autosomal trisomy) and several teratogenic or mutagenic factors, including, alcohol, smoking, drugs like-phenytoin. Maternal causes of spontaneous abortion could be increased maternal age, infections, medications, nutrition, occupational and environmental factors, uterine defects, immunological factors, inherited thrombophilia, hormonal insufficiency, endocrine disorders mainly diabetes mellitus and thyroid disorders, etc.
Pregnancy is associated with significant but reversible changes in thyroid functions. During pregnancy proper maternal thyroid function is important for both mother and fetus. Elevated maternal thyroid stimulating hormone (TSH) has been associated with an increased risk of preterm birth, placental abruption, fetal death, and impaired neurological development in the child.,, The presence of antibodies to thyroid peroxidase (TPO-Ab) has been associated with increased the risk of miscarriage., Thyroid dysfunctions are common in women during reproductive age with the prevalence of elevated TSH ranging from 4% to 9% and the prevalence of TPO-Ab ranging from 11.3% to 18% in the population.,
Women with hypothyroidism have decreased fertility, and if they conceive, they have increased the risk of abortion, along with the risk of gestational hypertension, anemia, abruption placenta and postpartum hemorrhage. Human placental development is itself responsive to thyroid hormone from early gestation with evidence of trophoblastic expression of thyroid hormone receptors. In humans, triiodothyronine (T3) has been shown to suppress apoptosis and down-regulate Fas and Fas-ligand expression. and thus promoting extravillous trophoblast invasion in the decidua. It has been postulated that abnormal thyroid hormone levels could give rise to increased increase to malplacentation which underlie the association between maternal thyroid dysfunction and adverse obstetric outcome. Colicchia et al. concluded that a the local action of thyroid hormones on female reproductive organs and embryo seemed to be crucial for a successful pregnancy and alterations of the highly regulated local activity of thyroid hormones may play an important role in early pregnancy and pregnancy loss.
Hypothyroidism has been documented to be associated with various reproductive disorders ranging from menstrual irregularities to infertility. Hypothyroidism is associated with an increased TRH production and hyperprolactinaemia. This further leads to a delayed luteinizing hormone response and inadequate corpus luteum formation. By affecting the peripheral oestrogen metabolism and also by decreasing sex hormone-binding globulin production, hypothyroidism may affect the fertility. Abalovich et al. showed that untreated hypothyroidism, subclinical or overt at the time of conception is associated with higher miscarriage rate as compared to euthyroid subjects. Ashoor et al. demonstrated a significant association between low maternal free thyroxine (FT4) during the first trimester and fetal loss, in pregnancies complicated by subclinical hypothyroidism. Thus, there is a need to screen pregnant women for subclinical hypothyroidism and thyroid autoimmunity, especially those women with a history of miscarriage. Hence, this study was designed to analyze thyroid hormone profile in pregnancy and its possible association with the risk of abortion during pregnancy.
| Methods|| |
This prospective observational study was carried out in 100 pregnant women with a singleton pregnancy of 6–12 weeks of gestation in the Department of Biochemistry in collaboration with Department of Obstetrics and Gynaecology during 2016. The patients were divided into three groups, namely, Group 1 (n = 30): Comprising normal pregnant women with no history of abortion (control group); Group 2 (n = 35): Comprising pregnant females with history of previous abortion and Group 3 (n = 35): Comprising of pregnant women coming with chief complaints of bleeding per vaginum.
Women who were not sure of dates, known case of diabetes mellitus, hypertension, thyroid disorder, renal or liver disease, autoimmune disorder, and multiple pregnancy were excluded from the study.
A detailed history and thorough general physical examination were carried out in all the pregnant women. Routine antenatal investigations were done at the time of first antenatal visit. A volume of 5 mL blood was drawn aseptically, and serum was separated by centrifugation. Routine investigations and total T3, total thyroxine (T4) and TSH levels were estimated in maternal blood by chemiluminescence. All the patients were followed every 4 weekly till 20 weeks and the outcome was noted in terms of anembryonic pregnancy, missed abortion, spontaneous abortion, or continuation of pregnancy. Data thus collected were presented as mean ± standard deviation and Statistical Package for the Social Sciences(SPPSS)/analysis of covariance (ANOVA) (IBM; Armonk, New York, United States) was applied.
| Results|| |
In this study, maximum number of women were between 21 and 25 years of age group. Mean age in Group 1, 2, and 3 were 21.63 ± 1.21, 22.6 ± 1.55, and 22.92 ± 2.31 years, respectively, and the difference between the mean age of patients in three groups was not statistically significant. The mean gestational age by dates in Group 1 was 8.86 ± 1.63 weeks, in Group 2 was 8.22 ± 1.55 weeks, and in Group 3 was 8.22 ± 1.33 weeks. Mean Hb in Group 1, 2, and 3 were 10.15 ± 1.09, 9.83 ± 0.88, and 10.64 ± 1.33 g/dl, respectively. The difference in the mean Hb in three groups was not statistically significant. In the present study, there was no significant difference between three groups on the basis of parity. The majority of patients in all the groups were primigravida (63.33% in Group 1, 68.57% in Group 2, and 68.57% in Group 3). The percentage of multigravida was 36.66% in Group 1; 31.42% each in Group 2 and 3.
Most of the patients in all three groups were Rh positive. Nearly 2% of patients in Group 1, 2.85% of patients in Group 2 and 5.71% of patients in Group 3 were Rh negative. The difference was not statistically significant.
In Group 1, all the patients were HIV and Venereal Disease Research Laboratory (VDRL) negative, whereas 3.33% of patients were positive for Australia antigen. 2.85% of patients in Group 2 were found to be reactive for each HIV, hepatitis B surface antigen (HBsAg) and VDRL. All patients in Group 3 were nonreactive for VDRL, whereas 2.85% of patients were reactive for HIV and HBsAg antigen. The difference between the HIV, HBsAg, and VDRL status between three groups was statistically insignificant.
[Table 1] shows mean thyroid profile of study population. It was observed that the mean T3 and T4 values in Group 1, 2, and 3 were comparable. However, the difference between T4 values of Group 1 and 2 was statistically significant (P = 0.04). Mean TSH levels in the first trimester in Group 1, 2 and 3 were comparable.
|Table 1: Distribution of patients according to thyroid profile in three groups|
Click here to view
[Table 2] shows the correlation of TSH with T3 and T4, respectively. TSH was significantly negatively correlated with T3 in all the three groups (r = −0.951 in Group 1, r = −0.951 in Group 2, and r = −0.563 in Group 3). TSH also showed a significant negative correlation with T4 in all the three groups (r = −0.563, r = −0.950, and r = −0.927 in Group 1, 2, and 3, respectively).
In [Table 3], in Group 1, 90% of euthyroid patients had normal pregnancy. From the total 9.99% hypothyroid patients, 6.66% aborted and only 3.33% continued with the pregnancy. This showed the strong association of TSH with abortion (P ≤ 0.001). In Group 2 and 3, 88.57% and 80% of euthyroid patients had normal pregnancy, respectively, while 2.85% euthyroid female from Group 3 aborted. Indicating that TSH was significantly associated with abortion in the present study (P ≤ 0.05).
Nearly 3.33% of patients ended up with anembryonic and spontaneous abortion each in Group 1; rest continued with pregnancy successfully. Whereas in Group 2, 88.58% of patients had a successful pregnancy, whereas 5.71% of cases resulted in anembryonic and missed abortion each. In Group 3, only 80.01% of cases continued with pregnancy, and 2.85% of cases had anembryonic abortion, and missed and spontaneous abortion occurred in 8.57% of cases each. The difference between all three groups in terms of the outcome of pregnancy was statistically insignificant.
| Discussion|| |
Fetal and placental growth were affected by thyroid dysfunction in early pregnancy. In the present study mean value of T3 and T4 were comparable in Group 1, 2, and 3 and the difference was not statistically significant. Mean TSH levels in the first trimester in Group 1 was 1.58 ± 0.76 mIU/L; in Group 2 and 3 were 1.92 ± 0.77 and 1.79 ± 0.90 mIU/L, respectively. The difference in the mean TSH value in the three groups was found to be statistically insignificant.
Donmez et al. and Rao et al. compared thyroid hormone levels in recurrent aborters with normal pregnant females and found significantly lower levels of T4 and T3 in the study group. This is in contrast to the present study. The reason for this could be that in present study patients with a history of abortion were included in Group 2 instead of those with recurrent abortions.
In Group 1, 90% (n = 27) of euthyroid patients had normal pregnancy. From the total 9.99% (n = 3) hypothyroid patients, 6.66% (n = 2) aborted and only 3.33% (n = 1) continued with pregnancy. Showing a strong association of TSH with abortion. In Group 2 and 3, 88.57% (n=31) and 80% (n=28) euthyroid patients had normal pregnancy, respectively, while 2.85% euthyroid female from Group 3 aborted showing an association of TSH with abortion.
Sharma et al. found a significant association of thyroid function with an abortion rate of 14.63% in their study group, i.e., pregnant women with hypothyroidism (and 4.96% in their control group). Furthermore, Abalovich et al. reported that when adequate treatment with levothyroxine was given, in the overtly hypothyroid pregnant females there were no abortions. However, when it was inadequate (in subclinically hypothyroid group), the abortion rate was 71.4%. In euthyroid group, the abortion rate was 4%.
Springer et al. have reported mean TSH levels in the first trimester to be 1.213 mIU/L in a study over of 4337 pregnant women (excluding those with a history of thyroid disease and autoimmunity). They attributed this to thyrotropic activity of elevated circulating human chorionic gonadotropin (HCG) concentration to be responsible for lower serum TSH levels, mainly in the first trimester.
In the present study, mean TSH in first trimester was negatively correlated with mean T3(r = −0.951, r = −0.951, and r = −0.972, respectively) and mean T4 values (r = −0.563, r = −0.950 and r = −0.927, respectively) in the three groups (P ≤ 0.01) [Table 3]. Various studies have reported a significant negative correlation between the TT4, TT3 and TSH levels (P ≤ 0.01) in normal pregnancy., Similarly, this study showed the significant inverse relationship between the TT4, TT3, and TSH indicating the existence of the feedback mechanism between the TSH and T4 production.
Various studies have shown that the inverse correlation between TSH and FT4 levels was due to thyrotropic properties of HCG. After an initial increase in the first 10 weeks of pregnancy, HCG levels subsequently decrease, leading to a decrease in FT4 and an increase in TSH levels. In addition, the high estrogen levels lead to a rise in T4-binding globulin levels, thereby increasing total T4 levels. Benhadi et al. found an inverse relationship between TSH and FT4. They considered HCG as a possible causative factor. HCG levels were used as a marker for abortion: women with low HCG were at a much higher risk of abortion. Ashoor et al. observed a negative correlation (r = −0.697) between TSH and FT4. The incidence of high TSH and low FT4 in the fetal loss group was higher than in normal outcome group. The findings of this study are in accordance with these reports.
In the present study also, the abortion rate was higher in the hypothyroid group as compared to euthyroid group (P < 0.05). TSH was found to be strongly associated with abortion in all the three groups (P < 0.001). TSH was found to be negatively correlated with T3 and T4 values in the three groups, respectively (P < 0.01). In the present study, 3.33% of patients ended up with anembryonic and spontaneous abortion each in Group 1; rest continued with pregnancy successfully. Whereas in Group 2, 88.58% of patients had successful pregnancy and 5.71% of cases resulted in anembryonic and missed abortion each. In Group 3, only 80.01% of cases continued with pregnancy and 2.85% of cases had anembryonic abortion, whereas missed and spontaneous abortion occurred in 8.57% of cases each. The difference between all three groups in terms of the outcome of pregnancy was statistically insignificant.
| Conclusion|| |
TSH levels were significantly higher in the first trimester in women who had spontaneous abortion as compared to pregnant women who had a successful continuation of pregnancy. TSH was strongly associated with abortion in the first trimester in all the three groups. Thus, screening of thyroid disorders in early pregnancy has clinical significance and adequate T4 replacement therapy if given in cases of hypothyroidism would help to reduce the risk of miscarriage in these women.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Regan L, Rai R. Epidemiology and the medical causes of miscarriage. Baillieres Best Pract Res Clin Obstet Gynaecol 2000;14:839-54.
Cunningham FG, Leveno KJ, Bloom SL, Spong CY, Dashe JS, Casey BM, et al
. Textbook of Williams Obstetrics. 24th
ed. New York: McGraw-Hill Co.; 2014. p. 350-76.
LaFranchi SH, Haddow JE, Hollowell JG. Is thyroid inadequacy during gestation a risk factor for adverse pregnancy and developmental outcomes? Thyroid 2005;15:60-71.
Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ, et al
. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 2005;105:239-45.
Allan WC, Haddow JE, Palomaki GE, Williams JR, Mitchell ML, Hermos RJ, et al
. Maternal thyroid deficiency and pregnancy complications: Implications for population screening. J Med Screen 2000;7:127-30.
Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al
. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N
Engl J Med 1999;341:549-55.
Poppe K1, Glinoer D. Thyroid autoimmunity and hypothyroidism before and during pregnancy. Hum Reprod Update 2003;9:149-61.
Stagnaro-Green A, Glinoer D. Thyroid autoimmunity and the risk of miscarriage. Best Pract Res Clin Endocrinol Metab 2004;18:167-81.
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med 2000;160:526-34.
Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, et al
. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002;87:489-99.
Abalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid 2002;12:63-6.
Laoag-Fernandez JB, Matsuo H, Murakoshi H, Hamada AL, Tsang BK, Maruo T. 3,5,3'-triiodothyronine down-regulates Fas and Fas ligand expression and suppresses caspase-3 and poly (adenosine 5'-diphosphate-ribose) polymerase cleavage and apoptosis in early placental extravillous trophoblasts in vitro
. J Clin Endocrinol Metab 2004;89:4069-77.
Colicchia M, Campagnolo L, Baldini E, Ulisse S, Valensise H, Moretti C. Molecular basis of thyrotropin and thyroid hormone action during implantation and early development. Hum Reprod Update 2014;20:884-904.
Ashoor G, Maiz N, Rotas M, Jawdat F, Nicolaides KH. Maternal thyroid function at 11 to 13 weeks of gestation and subsequent fetal death. Thyroid 2010;20:989-93.
Sardana D, Nanda S, Kharb S. Thyroid hormones in pregnancy and preeclampsia. J Turk Ger Gynecol Assoc 2009;10:168-71.
Donmez M, Tolga S, Alev A, Yazuv A. Spontaneous abortion and thyroid functions. Perinatol J 2005;13:110-3.
Rao VR, Lakshmi A, Sadhnani MD. Prevalence of hypothyroidism in recurrent pregnancy loss in first trimester. Indian J Med Sci 2008;62:357-61.
] [Full text]
Sharma PP, Mukhopadhyay P, Mukhopadhyay A, Muraleedharan PD, Begum N. Hypothyroidism in pregnancy. J Obstet Gynaecol India 2007;57:331-4.
Springer D, Zima T, Limanova Z. Reference intervals in evaluation of maternal thyroid function during the first trimester of pregnancy. Eur J Endocrinol 2009;160:791-7.
Glinoer D. The regulation of thyroid function in pregnancy: Pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997;18:404-33.
Rodien P, Jordan N, Lefèvre A, Royer J, Vasseur C, Savagner F, et al
. Abnormal stimulation of the thyrotrophin receptor during gestation. Hum Reprod Update 2004;10:95-105.
Alexander EK. Thyroid autoantibodies and pregnancy risk. Nat Rev Endocrinol 2011;7:54-6.
Benhadi N, Wiersinga WM, Reitsma JB, Vrijkotte TG, Bonsel GJ. Higher maternal TSH levels in pregnancy are associated with increased risk for miscarriage, fetal or neonatal death. Eur J Endocrinol 2009;160:985-91.
[Table 1], [Table 2], [Table 3]