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Table of Contents
ORIGINAL ARTICLE
Year : 2018  |  Volume : 8  |  Issue : 1  |  Page : 41-43

Abortion may be associated with elevated risk of future hypothyroidism


Department of Medicine, Dr. RPGMC, Kangra, Tanda, Himachal Pradesh, India

Date of Web Publication9-Mar-2018

Correspondence Address:
Dr. Vivek Chauhan
Department of Medicine, Dr. RPGMC, Kangra, Tanda, Himachal Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJCIIS.IJCIIS_43_17

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   Abstract 


Objective: Fetal microchimerism during pregnancy and abortion has been linked with autoimmune hypothyroidism in females. We conducted a case–control study to investigate the odds of “abortion in the past” in the newly diagnosed hypothyroid females compared to their age-matched euthyroid controls.
Methods: All consecutive newly diagnosed hypothyroid females, over 1 year, were enrolled as cases. Age-matched euthyroid controls were selected from the same region. The exposure variable tested was “past history of abortion (elective or therapeutic).”
Results: Totally, 120 cases and 172 controls were recruited over 1 year with a mean age of 42.2 ± 9.8 years and 41.1 ± 12.4 years, respectively. The exposure variable (abortion) was present in 71 (59%) cases and 10 (6%) controls. Odds ratio (OR): 23.5 (12.2–48.9) P < 0.0001. Autoimmunity, based on thyroid peroxidase (TPO) positivity (TPO levels ≥30 U/ml), was present in 92 (77%) of the cases; TPO was negative in 28 (33%) of cases. The exposure variable was documented in 62.4% and 50% of TPO positive and negative cases, respectively (P = 0.28).
Discussion and Conclusion: The study suggests that abortion (elective or therapeutic) in the past is strongly associated with newly diagnosed hypothyroidism in females aged 42.2 ± 9.8 years; OR: 23.5 (P < 0.0001). Interestingly, abortion was associated with both, TPO positive and negative hypothyroidism.

Keywords: Autoimmunity, endocrinology, Hashimoto's, hormone, miscarriage, parity, thyroid


How to cite this article:
Chauhan V, Thakur A, Sharma G. Abortion may be associated with elevated risk of future hypothyroidism. Int J Crit Illn Inj Sci 2018;8:41-3

How to cite this URL:
Chauhan V, Thakur A, Sharma G. Abortion may be associated with elevated risk of future hypothyroidism. Int J Crit Illn Inj Sci [serial online] 2018 [cited 2019 Dec 11];8:41-3. Available from: http://www.ijciis.org/text.asp?2018/8/1/41/227056




   Introduction Top


Hypothyroidism is very well known to lead to abortions.[1] The reverse association of parity and abortions with future risk of hypothyroidism has also been recently shown to exist.[2],[3] Fetal microchimerism that occurs after pregnancy and abortions has been shown to be responsible for this.[4] Fetal microchimerism is defined as the presence of fetal cells in maternal tissues.[5] Although fetal cells enter maternal circulation in most pregnancies, the fetal loss (abortion) is more likely to induce fetal microchimerism.[6] Some investigators, however, believe that microchimeric cells are the innocent bystanders and are not responsible for hypothyroidism in females.[7] We conducted a case–control study to investigate the odds of “abortion in the past” in the newly diagnosed hypothyroid females compared to their age-matched euthyroid controls.


   Methodology Top


Type of study

Case–control study; duration: 1 year (January–December 2016); setting: Department of Medicine, Tertiary care 785 bedded teaching hospital in the Sub-Himalayan Region of North India

Null hypothesis

The odds of a past abortion in newly diagnosed hypothyroid females are not significantly higher than that in their age-matched euthyroid females.

Alternative hypothesis

The odds of a past abortion in newly diagnosed hypothyroid females are significantly higher than that in their age-matched euthyroid females.

Definitions

Newly diagnosed hypothyroidism

It was defined as the signs and symptoms suggestive of hypothyroidism along with the biochemical values of serum thyroid stimulating hormone (TSH) levels of ≥5 mIU/L in the presence of low free T3 or free T4. Clinical features were noted for all hypothyroid females.

Autoimmunity

It was defined positive when thyroid peroxidase (TPO) antibody level was ≥30 U/ml.

Exclusion criteria

In the absence of signs and symptoms suggestive of hypothyroidism, patients with serum TSH level of <10 mIU/L and normal free T3/free T4 were excluded from the study.

Cases

We enrolled all consecutive newly diagnosed married hypothyroid females presenting in the Department of Medicine over 1 year as the cases.

Controls

Age-matched controls were selected by a convenient random sampling from the females attending the outpatient Department of Medicine for minor unrelated complaints. Hypothyroidism (TSH level >5 mIU/L) was ruled out in controls. Controls belonged to the same geographic area as the cases.

Exposure variable

We checked the exposure variable, i.e., past abortion (elective or therapeutic) in the cases and controls.

Statistical analysis

The data were analyzed using SPSS software (version 23, SPSS, Inc., Chicago, IL, USA). The continuous variables were expressed as means and standard deviations, and categorical variables were expressed as proportions. The comparison of continuous variables was done using t- test, and categorical variables were compared using Fisher's exact. An alpha error of 95% was considered statistically significant (P < 0.05).

Approval from ethics committee was obtained for this study, and informed consent was obtained from the participants before enrollment.


   Results Top


Newly diagnosed hypothyroid females

We enrolled 120 married females with newly diagnosed hypothyroidism as the cases, and 176 age-matched euthyroid married females as the controls. Cases and controls had a mean age 42.2 ± 9.8 years and 41.1 ± 12.4 years, respectively, they shared a similar socioeconomic and cultural background.

Mean TSH of the cases and controls was 31.7 ± 26.6 mIU/L (range 8–100 mIU/L) and 2.28 ± 0.87 (range 0.5–4.5 mIU/L) (P < 0.0001).

The exposure variable, i.e. the history of abortion (elective or therapeutic) was present in 71 (59%) cases and 10 (6%) controls. Odds ratio (OR): 23.5 (12.2–48.9) P < 0.0001 [Table 1].
Table 1: 2×2 table for newly diagnosed hypothyroid females versus control euthyroid females

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TPO positivity and negativity among the cases were documented in 92/120 (77%) and 29/120 (33%), respectively. A history of past abortion among TPO positive and negative hypothyroid cases was 57/92 (62%) and 14/28 (50%), respectively (P = 0.28).

Other important signs among the hypothyroid cases were loss of lateral third of eyebrows in 14 (11.5%), goiter in 4 (3.3%), slowness of speech in 31 (25.8%), and delayed relaxation of Achilles tendon reflex in 27 (22.5%) females.


   Discussion Top


Hypothyroidism leads to abortions and stillbirths; this is known for long.[1] The reverse phenomenon that abortion leads to hypothyroidism in later life is a relatively new finding in biology.[5] Studies show that abortions and parity are both associated with future autoimmune diseases in females.[4] This association was strongest for the autoimmune hypothyroidism.[2],[3],[4],[5],[6],[8]

The available evidence is contradictory; some show a positive association of parity with future hypothyroidism;[2],[3] others show no association.[9],[10]

Our case–control study showed a significant association between newly diagnosed hypothyroidism and past abortions in females living in the Sub-Himalayan Region of North India. OR of 23.5 and P < 0.0001.

Fetal microchimerism has been held responsible for the development of autoimmunity in females. It becomes established during pregnancy and is aided by the maternal immune suppression in pregnancy by the placenta.[5] Fetal microchimerism may persist in the postpartum period for decades after the last pregnancy or abortion.[7] High OR (23.5; P < 0.001) for past abortion in the cases aged 42.2 ± 9.8 years, in our study, shows that the risk for hypothyroidism persists for a lifetime after an abortion.

The identification of fetal cells that persist preferentially in maternal tissues subject to autoimmunity, such as skin and thyroid, has also suggested the possible immune modulation of the autoimmune response at the target tissue by fetal cells.[5],[8] The exact mechanism of fetal microchimerism leading to autoimmune hypothyroidism is yet unclear. There are 4 possible hypotheses related to microchimerism with sufficient supporting evidence for each one of them:[11] (1) microchimerism-induced graft versus host reaction; (2) microchimerism Induced host versus graft reaction; (3) microchimeric cells repair injured tissues resulting in their concentration in injured tissues; and (4) microchimeric cells are innocent bystanders.

TPO positive and negative females had a history of past abortion 62% and 50%, respectively (P = 0.28); thus, abortion is equally associated with TPO positive and negative forms of hypothyroidism. This is a new finding and needs corroboration in a larger sample size study.

Limitations

This is a clinical study done in a single center. Controls were selected as a convenient random sample from the outpatient department. The controls were matched only for age but not for other variables such as hypertension, diabetes, and dyslipidemia.

Strengths

A total of 120 newly diagnosed females were studied over 1 year as cases, which is a large enough sample to conduct a case–control study. The controls were age-matched and belonged to the same geographic region as controls.


   Conclusion Top


Our study suggests that abortion (elective or therapeutic) in the past is strongly associated with newly diagnosed hypothyroidism in females aged 42.2 ± 9.8 years. OR: 23.5 (P < 0.0001). Interestingly, abortion was associated with both, TPO positive and negative hypothyroidism.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Zhang Y, Wang H, Pan X, Teng W, Shan Z. Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: A systematic review and meta-analysis. PLoS One 2017;12:e0175708.  Back to cited text no. 1
[PUBMED]    
2.
Friedrich N, Schwarz S, Thonack J, John U, Wallaschofski H, Völzke H. Association between parity and autoimmune thyroiditis in a general female population. Autoimmunity 2008;41:174-80.  Back to cited text no. 2
    
3.
Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L, Rasmussen LB, et al. Development of autoimmune overt hypothyroidism is highly associated with live births and induced abortions but only in premenopausal women. J Clin Endocrinol Metab 2014;99:2241-9.  Back to cited text no. 3
    
4.
The Role of Fetal Microchimerism in Autoimmune Disease. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2894651/. [Last accessed on 2017 May 13].  Back to cited text no. 4
    
5.
Ando T, Davies TF. Clinical review 160: Postpartum autoimmune thyroid disease: The potential role of fetal microchimerism. J Clin Endocrinol Metab 2003;88:2965-71.  Back to cited text no. 5
    
6.
Khosrotehrani K, Johnson KL, Lau J, Dupuy A, Cha DH, Bianchi DW. The influence of fetal loss on the presence of fetal cell microchimerism: A systematic review. Arthritis Rheum 2003;48:3237-41.  Back to cited text no. 6
    
7.
O'Donoghue K. Pregnancy and the risk of autoimmune disease: An exploration. Chimerism 2011;2:84-5.  Back to cited text no. 7
    
8.
Klintschar M, Immel UD, Kehlen A, Schwaiger P, Mustafa T, Mannweiler S, et al. Fetal microchimerism in Hashimoto's thyroiditis: A quantitative approach. Eur J Endocrinol 2006;154:237-41.  Back to cited text no. 8
    
9.
Walsh JP, Bremner AP, Bulsara MK, O'Leary P, Leedman PJ, Feddema P, et al. Parity and the risk of autoimmune thyroid disease: A community-based study. J Clin Endocrinol Metab 2005;90:5309-12.  Back to cited text no. 9
    
10.
Sgarbi JA, Kasamatsu TS, Matsumura LK, Maciel RM. Parity is not related to autoimmune thyroid disease in a population-based study of Japanese-Brazilians. Thyroid 2010;20:1151-6.  Back to cited text no. 10
    
11.
Lepez T, Vandewoestyne M, Deforce D. Fetal microchimeric cells in autoimmune thyroid diseases: Harmful, beneficial or innocent for the thyroid gland? Chimerism 2013;4:111-8.  Back to cited text no. 11
    



 
 
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