|Year : 2015 | Volume
| Issue : 2 | Page : 402-405
Anti-thyroid peroxidase antibody positivity during early pregnancy is associated with pregnancy complications and maternal morbidity in later life
Raghunath Bhattacharyya1, Kasturi Mukherjee2, Anjan Das3, Madhuri Ranjana Biswas3, Sandip Roy Basunia3, Anindya Mukherjee4
1 Department of G and O, College of Medicine and Sagore Dutta Hospital, Kolkata, West Bengal, India
2 Department of Biochemistry, Kolkata Medical College, Kolkata, West Bengal, India
3 Department of Anaesthesiology, College of Medicine and Sagore Dutta Hospital, Kolkata, West Bengal, India
4 Department of Anaesthesiology, Nil Ratan Sircar Medical College and Hospital, Kolkata, West Bengal, India
|Date of Web Publication||6-Jul-2015|
Dr. Anjan Das
174, Gorakshabashi Road, Royal Plaza Apartment 4th Floor, Flat No. 1, Nagerbazar, Kolkata - 700 028, West Bengal
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Aims: We assessed the impact of detecting anti-thyroid peroxidase antibodies (anti-TPO-Ab) in the first trimester of pregnancy on pregnancy outcomes and maternal thyroid function during the postpartum period. Materials and Methods: In a prospective study consisting 400 pregnant women (8-12 weeks pregnant) were screened for their thyroid profile and followed-up to 12 weeks postpartum. Patients with abnormal thyroid function at 12 weeks postpartum were further followed-up with repeated assessment of thyroid stimulating hormone (TSH) and serum-free thyroxine-4 levels at 8 weeks interval up to 12 months postpartum. Results: 11.5% of the subjects were positive for anti-TPO-Ab who had mean TSH level of 2.31 μIU/ml, which was significantly (P- 0.0001) higher than pregnant women negative for anti-TPO-Ab (1.73 μIU/ml). Increased incidence of miscarriage was observed in anti-TPO positive mothers when compared to antibody negative mothers. Postpartum thyroid dysfunction developed in 4.7% cases at 12 weeks, among them antibody positivity was observed in 81.25% of subjects. In 18.75% mothers positive for anti-TPO-Ab, the thyroid dysfunction persisted up to 12 months postpartum. Conclusions: Thyroid antibodies detected in early pregnancy seems to be predicting pregnancy complications and later maternal thyroid disease related morbidity.
Keywords: Outpatient department, postpartum thyroid dysfunction, postpartum thyroiditis, thyroid peroxidase antibody
|How to cite this article:|
Bhattacharyya R, Mukherjee K, Das A, Biswas MR, Basunia SR, Mukherjee A. Anti-thyroid peroxidase antibody positivity during early pregnancy is associated with pregnancy complications and maternal morbidity in later life. J Nat Sc Biol Med 2015;6:402-5
|How to cite this URL:|
Bhattacharyya R, Mukherjee K, Das A, Biswas MR, Basunia SR, Mukherjee A. Anti-thyroid peroxidase antibody positivity during early pregnancy is associated with pregnancy complications and maternal morbidity in later life. J Nat Sc Biol Med [serial online] 2015 [cited 2021 Mar 4];6:402-5. Available from: http://www.jnsbm.org/text.asp?2015/6/2/402/160021
| Introduction|| |
Thyroid peroxidase (TPO), is a membrane-bound enzyme, which catalyzes iodide oxidation and iodination of tyrosyl residues of thyroglobulin. ,, Anti-TPO-antibody (anti-TPO-Ab) can react with TPO, leading to the destruction of thyrocytes. Autoantibodies to TPO are common in the euthyroid population and are associated with major alterations in the course of pregnancy affecting the mother, fetus, and/or neonate. Although the presence of TPO-Ab is associated with increased rate of pregnancy complications such as miscarriage, placental abruption, pregnancy-induced hypertension, and preterm delivery,  these relationships are not proved in all studies. Women with high antibody titer in early pregnancy are commonly affected with postpartum thyroid dysfunction (PPTD)  with its potential impact on future pregnancies.
We conducted this study in tertiary care hospital to evaluate the incidence of TPO-Ab positivity in women attending antenatal outpatient department (OPD), to determine the effects of presence of thyroid antibody (anti-TPO-Ab) in antenatal period on pregnancy outcomes, the incidence of PPTD and its natural course.
| Materials and Methods|| |
The present study was undertaken in a tertiary care institute from April 2011 to October 2012, where consecutive 400 pregnant women from booked antenatal cases were screened. The study was approved by Institute's Ethics Committee following which subjects were enrolled after adequate informed consent was obtained. In this prospective cohort study, mothers with a singleton pregnancy without any sorts of known previous thyroid disorder were included. Mothers with pregnancy in congenitally malformed uterus, fibroid uterus, known cervical incompetence, and history of smoking were excluded.
Serum Free T 4 , Free T 3 , and thyroid-stimulating hormone (TSH) and serum anti-TPO-Ab levels were measured routinely in their first antenatal visit (median gestational age at sampling was 10 weeks). Thorough and detailed history of each case was recorded. Special importance were given to detailed obstetric history; medical history of autoimmune diseases, diabetes, previous history of miscarriage, family history of diabetes, autoimmune thyroid diseases, and other autoimmune diseases. They were closely monitored in the antenatal clinic and the labor ward following admission. All subjects were followed-up in OPD during routine postnatal visit. Serum Free T 4 and TSH levels were repeated in all cases routinely at 12 weeks after delivery. All subjects with abnormal thyroid function at 12 weeks postpartum were followed-up with repeated serum Free T 4 and TSH levels at 8 weeks interval up to 12 months postpartum (telephonic contact was maintained). During follow-up visits, complaints are noted carefully with special reference to signs of thyroid diseases. Endocrinology consultations were also done.
Normal reference range in pregnancy (as per our hospital reference value)
Thyroid-stimulating hormone: 0.35-2.5 μIU/ml; Free T 3 : 2.3-4.2 pg/dl; Free T 4 : 0.89-1.7 ng/dl
Postpartum hypothyroidism may be defined as either a serum TSH concentration >3.6 μIU/ml together with a free T 4 <0.6 ng/dl or a TSH ≥10 μIU/ml
Serum Free T 4 , Free T 3 , and TSH level were measured by ELISA; serum anti-TPO-Ab levels were measured by chemiluminescence.
Statistical analysis was performed by Graphpad prism software(GraphPad Software, Inc. San Diego, CA 92130; USA). All the data are normally distributed. Categorical variables were compared between groups by Chi-square test; numerical variables were compared by Student's t-test. All analyses were two-tailed and P < 0.05 was considered to be statistically significant.
| Results|| |
Of the 400 antenatal mothers screened for thyroid status, the postpartum follow-up records were incomplete in 38 cases, and these were excluded from the study [Figure 1].
Of 400 antenatal mothers, 46 detected positive for anti-TPO-Ab, giving an incidence rate of 11.5%. The incidence of subclinical hypothyroidism in mothers attending our antenatal clinic was 5.25% (21 out of 400). The percentage of anti-TPO-Ab positivity in euthyroid mothers was 11.34% (43 out of 379) and the percentage of anti-TPO-Ab positivity in cases of subclinical hypothyroid antenatal mothers was 14.28% (3 out of 21).
Totally, 41 mothers (9 TPO-Ab positive and 32 TPO-Ab negative) with TSH level of >2.5 μIU/ml received Levothyroxine therapy. It was started at a dose of 25 mcg/day as per endocrinologist recommendation and the final dose was titrated according to next thyroid profile. It was noted that the average dose of Levothyroxine required was significantly higher in TPO-Ab positive patients [Table 1].
About 38.24% anti-TPO-Ab positive mothers were <25 years age group. Antibody positivity was observed in 2.17% (1 out of 46) of women, which was associated with autoimmune medical disorder.
Mean serum TSH level was significantly (P < 0.0001) higher (2.31 vs. 1.73 μIU/ml) among TPO-Ab positive than negative mothers. Increased incidence of past history miscarriage was observed in TPO-Ab positive mothers than in antibody negative mothers [Table 1].
In our study, 10.87% of anti-TPO-Ab positive mothers had a spontaneous abortion and in case of anti-TPO-Ab negative mothers, it was 4.8%, however, this difference was not statistically significant (P = 0.16) [Table 2]. Again 14.28% of anti-TPO-Ab positive mothers had preterm delivery and in case of anti-TPO-Ab negative mothers, it was 8.6% (P = 0.496) [Table 2].
Postpartum thyroid dysfunction developed in 16 cases (incidence of 4.7%). Among them, antibody positivity was observed in 81.25% subjects [Table 3]. Of 16 mothers who were found to have PPTD at 12 weeks, 3 mothers persisted the disorder up to 12 months postpartum. During the course of PPTD, hypothyroidism was observed in 31.23% (5 out of 16), hyperthyroidism alone observed in 25% (4 out of 16) and hyperthyroidism followed by subclinical hypothyroidism was observed in 43.75% (7 out of 16) of cases. Average duration of PPTD was about 7 months. Symptoms present at the time of detection of PPTD were vague and nonspecific (fatigue, irritability, lethargy, etc.). 6.25% (1 out of 16) women develop a small painless goiter. 18.75% (3 out of 16) of cases who developed PPTD required Levothyroxine therapy.
| Discussion|| |
The presence of thyroid autoantibodies is nonspecific, being present in up to 20% of biochemically euthyroid pregnant women. ,, However, 10% of normal adults have high serum anti-TPO-Ab concentrations, and the prevalence increases up to 30% among elderly.  In our study, the percentage of anti-TPO-Ab positivity in mothers attending antenatal clinic was 11.5%.
In a previous survey of pregnant women, 2% had subclinical hypothyroidism and 58% of had high anti-TPO-Ab concentration.  While in our study, only 14.28% had high anti-TPO-Ab concentration. This may be due to the iodine deficiency which is the most common cause of hypothyroidism in our country in comparison to autoimmune thyroid disorders. 
It is noted that the thyroid antibody titers remain very low with the TSH level >2 μIU/L. The titer rises with the TSH level beyond 2 μIU/L or higher.  In our study, TSH level in majority of TPO-Ab positive cases was 2 μIU/ml, which was significantly different (P-0.001) between TPO-Ab (+)ve and (-)ve groups [Table 1].
The association between thyroid autoimmunity and increased fetal loss is previously reported. , In our study as well, although not statistically significant (P = 0.16), anti-TPO-Ab positive mothers had a higher spontaneous abortion rate than anti-TPO-Ab negative mothers (10.87% vs. 4.8%, respectively). TPO-Ab-positive women had a significant increase in preterm delivery compared with antibody-negative women (26.8 vs. 8.0%, P = 0.01),  which is consistent with our observation (14.28 vs. 8.6% respectively).
The biphasic biochemical pattern (initial thyrotoxicosis due to an excessive release of preformed thyroid hormone, followed by hypothyroidism) is observed in almost 90% of patients, ,, while a variable incidence from 3% to 17% is reported worldwide. , Women with thyroid antibodies in the first trimester have a 33-50% chance of having postpartum thyroiditis (PPT). , Regarding the incidence of PPTD, the result of our study (4.7%) is lower than previous reports, which may be because we had screened all the subjects only once (at 12 weeks postpartum) and hence could have missed the cases who may have developed PPTD in later weeks of postpartum period. In our study, significantly (P = 0.0001) higher number of the antibody-positive mother (30.95% vs. 1.006%) developed PPTD [Table 3].
Quantitative evaluation of depressive symptomatology shows an increase of mild to moderate depression in thyroid antibody positive women even when they remain euthyroid during the postpartum period.  Several studies from different countries have shown that about 12-61% of women who develop postpartum hypothyroidism become chronically hypothyroid. , In those women who do not develop permanent hypothyroidism, the chance of experiencing a recurrence of PPTD after a previous episode is around 70%.  In this study, 18.75% mothers persisted the disorder up to 12 months postpartum.
The main limitation in our study is the time of recruiting participants at 8-12 weeks of gestation (median 10 weeks), as most abortions or pregnancy loss occur before 8 th week of gestation.
Despite the controversy around screening for postpartum thyroiditis measurement of serum soluble CD4 concentration drawn in the 1 st month postpartum may prove an ideal test for population screening for impending PPT.  Long-term follow-up of women who had an episode of PPT reveals a 20-40% incidence of permanent primary hypothyroidism. Identifying the women at increased risk for developing permanent hypothyroidism  will help in its prevention and better clinical management. Moreover, the test for anti-TPO-Ab is cheap and not associated with any ethical issues. A recent review of selenium concluded that selenium administration is effective in decreasing the TPO-Ab titer, incidence of PPT, and permanent hypothyroidism.  Nevertheless, treatment of TPO-Ab positive women with selenium to prevent PPT remains premature.
| Conclusion|| |
Thyroid antibodies detected in early pregnancy seem to predict pregnancy complications and later thyroid disease morbidity of the mother. Hence, screening should include an anti-TPO-Ab titer and TSH level, as the presence of antibody identifies women with much increased risk of developing pregnancy complications and postpartum thyroiditis.
| References|| |
Weetman AP, McGregor AM. Autoimmune thyroid disease: Further developments in our understanding. Endocr Rev 1994;15:788-830.
McLachlan SM, Rapoport B. The molecular biology of thyroid peroxidase: Cloning, expression and role as autoantigen in autoimmune thyroid disease. Endocr Rev 1992;13:192-206.
Ui N. Chemistry of thyroglobulin: Current research. Horumon To Rinsho 1972;20:3-7.
Karakosta P, Alegakis D, Georgiou V, Roumeliotaki T, Fthenou E, Vassilaki M, et al.
Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. J Clin Endocrinol Metab 2012;97:4464-72.
Swelam Eel S, Bakr HG, Mansour MA. Postpartum thyroid dysfunction: A state of immunological dysregulation. Clin Lab 2011;57:731-9.
O′Leary PC, Boyne P, Atkinson G, Mileham KJ, James I. Longitudinal study of serum thyroid hormone levels during normal pregnancy. Int J Gynaecol Obstet 1992;38:171-9.
Stagnaro-Green A, Roman SH, Cobin RH, el-Harazy E, Alvarez-Marfany M, Davies TF. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA 1990;264:1422-5.
Thyroid disease in pregnancy. ACOG Technical Bulletin Number 181 - June 1993. Int J Gynaecol Obstet 1993;43:82-8.
Mariotti S, Sansoni P, Barbesino G, Caturegli P, Monti D, Cossarizza A, et al.
Thyroid and other organ-specific autoantibodies in healthy centenarians. Lancet 1992;339:1506-8.
Klein RZ, Haddow JE, Faix JD, Brown RS, Hermos RJ, Pulkkinen A, et al.
Prevalence of thyroid deficiency in pregnant women. Clin Endocrinol (Oxf) 1991;35:41-6.
Fister P, Gaberscek S, Zaletel K, Krhin B, Hojker S, Gersak K. Thyroid function in the third trimester of pregnancy and after delivery in an area of adequate iodine intake. Int J Gynaecol Obstet 2011;112:52-5.
Abramson J, Stagnaro-Green A. Thyroid antibodies and fetal loss: An evolving story. Thyroid 2001;11:57-63.
Ghafoor F, Mansoor M, Malik T, Malik MS, Khan AU, Edwards R, et al.
Role of thyroid peroxidase antibodies in the outcome of pregnancy. J Coll Physicians Surg Pak 2006;16:468-71.
Shahbazian HB, Sarvghadi F, Azizi F. Prevalence and characteristics of postpartum thyroid dysfunction in Tehran. Eur J Endocrinol 2001;145:397-401.
Barca MF, Knobel M, Tomimori E, Cardia MS, Medeiros-Neto G. Prevalence and characteristics of postpartum thyroid dysfunction in São Paulo, Brazil. Clin Endocrinol (Oxf) 2000;53:21-31.
Walfish PG, Meyerson J, Provias JP, Vargas MT, Papsin FR. Prevalence and characteristics of post-partum thyroid dysfunction: Results of a survey from Toronto, Canada. J Endocrinol Invest 1992;15:265-72.
Hurtado-Hernández Z, Segura-Domínguez A. Postpartum thyroiditis. A review. Semergen 2013;39:272-8.
Stagnaro-Green A. Approach to the patient with postpartum thyroiditis. J Clin Endocrinol Metab 2012;97:334-42.
Glinoer D. The regulation of thyroid function in pregnancy: Pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997;18:404-33.
Glinoer D. The regulation of thyroid function during normal pregnancy: Importance of the iodine nutrition status. Best Pract Res Clin Endocrinol Metab 2004;18:133-52.
Kuijpens JL, Vader HL, Drexhage HA, Wiersinga WM, van Son MJ, Pop VJ. Thyroid peroxidase antibodies during gestation are a marker for subsequent depression postpartum. Eur J Endocrinol 2001;145:579-84.
Fung HY, Kologlu M, Collison K, John R, Richards CJ, Hall R, et al.
Postpartum thyroid dysfunction in Mid Glamorgan. Br Med J (Clin Res Ed) 1988;296:241-4.
Muller AF, Drexhage HA, Berghout A. Postpartum thyroiditis and autoimmune thyroiditis in women of childbearing age: Recent insights and consequences for antenatal and postnatal care. Endocr Rev 2001;22:605-30.
Lazarus JH, Ammari F, Oretti R, Parkes AB, Richards CJ, Harris B. Clinical aspects of recurrent postpartum thyroiditis. Br J Gen Pract 1997;47:305-8.
Balázs C, Farid NR. Soluble CD4 concentrations predict relapse of post-partum thyroiditis. J Endocrinol Invest 2002;25:11-7.
Premawardhana LD, Parkes AB, Ammari F, John R, Darke C, Adams H, et al.
Postpartum thyroiditis and long-term thyroid status: Prognostic influence of thyroid peroxidase antibodies and ultrasound echogenicity. J Clin Endocrinol Metab 2000;85:71-5.
Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab 2007;92:1263-8.
[Table 1], [Table 2], [Table 3]
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