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ORIGINAL ARTICLE
Year : 2016  |  Volume : 13  |  Issue : 1  |  Page : 1-4

Pregnancy outcomes in subclinical hypothyroidism and thyroid autoimmunity


Department of Endocrinology, Andhra Medical College, King George Hospital, Visakhapatnam, Andhra Pradesh, India

Date of Web Publication5-Jan-2016

Correspondence Address:
Suhitha Chittamuri
Department of Endocrinology, Andhra Medical College, King George Hospital, Visakhapatnam - 530 002, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-0354.168893

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  Abstract 

Context: This is a study on “pregnancy outcomes in subclinical hypothyroidism (SCH) and thyroid autoimmunity,” as the data from previous Indian studies is inconclusive. Aims: The aims were to evaluate pregnancy outcomes in SCH and to compare outcomes with and without thyroid peroxidase antibodies (TPOAbs). We also looked at pregnancy outcomes in euthyroid in relation to TPOAb. Design: This is an observational, prospective, cohort study. Subjects and Methods: One Hundred (50 SCH and 50 euthyroid) pregnant women are recruited in the study. Samples are analyzed for thyroid stimulating hormone, free T4, and TPOAb. SCH women are treated with levothyroxine. Pregnancy outcomes that are, miscarriage, pregnancy induced hypertension (PIH), gestational diabetes, preterm (PT) delivery, cesarean section (CS), Apgar score, and birth weight are recorded in follow-up. Statistical Analysis: Unpaired t-test and standard error of the difference between proportions are used for statistical analysis. P < 0.05 is considered as significantResults: Pregnancy outcomes between cases and controls, TPOAb positive and negative cases are similar. However, there is a significant increase of PT deliveries (10% vs. 0) and CS (36.73% vs. 15%) in cases when compared to TPOAb negativecontrols. PIH (6.67% vs. 0) is significantly higher in TPOAb positive controls when compared to TPOAb negative controls. Conclusions: Adverse pregnancy outcomes are not significantly higher in treated SCH when compared to euthyroid women, and TPOAb status have not affected the outcomes in SCH. However, there are significantly higher PT deliveries and need for CS in SCH compared to TPOAb negative euthyroid women. Euthyroid women with TPOAb are associated with significantly higher risk of PIH.

Keywords: Pregnancy outcomes, subclinical hypothyroidism, thyroid peroxidase antibodies


How to cite this article:
Chittamuri S, Bongi V, Ayyagari M, Kandregula DK, Kandregula SA. Pregnancy outcomes in subclinical hypothyroidism and thyroid autoimmunity. Thyroid Res Pract 2016;13:1-4

How to cite this URL:
Chittamuri S, Bongi V, Ayyagari M, Kandregula DK, Kandregula SA. Pregnancy outcomes in subclinical hypothyroidism and thyroid autoimmunity. Thyroid Res Pract [serial online] 2016 [cited 2019 Jun 26];13:1-4. Available from: http://www.thetrp.net/text.asp?2016/13/1/1/168893


  Introduction Top


Hypothyroidism affects 3–5% of all pregnant women and the prevalence of subclinical hypothyroidism (SCH) (2–3%) is much higher than that of overt hypothyroidism (0.3–0.5%). Thyroid autoantibodies are found in 5–15% of women during childbearing age.[1] Many studies have examined maternal and fetal complication rates in treated and untreated SCH to clarify whether all pregnant women with thyroid dysfunction needs treatment. Negro et al. noted an overall decrease in a composite of adverse pregnancy outcomes in the group treated with levothyroxine (LT4).[2] A recent study by Lazarus and colleagues did not show any differences in preterm (PT) delivery rates or birth weight between the treated and untreated groups of SCH.[3] The American Thyroid Association (ATA) recommends that evidence is fair to treat thyroid peroxidase antibody (TPOAb) positive pregnant women with SCH and insufficient to for or against routinely providing LT4 treatment in TPOAb negative pregnant women with SCH.[4] The Endocrine Society panel also recommends a LT4 replacement in women with SCH irrespective of TPOAb status; evidence is fair for obstetrical outcome and poor for neurological outcome.[5]

In view of the discrepancy in studies, the present study is designed to evaluate pregnancy outcomes in women with SCH and thyroid autoimmunity.


  Subjects and Methods Top


This is an observational, prospective, Cohort Study conducted in the Departments of Endocrinology and Obstetrics and Gynecology at a South Indian Tertiary Care Hospital. The present study recruited 100 pregnant women, of whom 50 are SCH cases, and the other 50 are euthyroid controls. [Figure 1] depicts the design of the current study. Singleton pregnant women aged ≥18 years with thyroid stimulating hormone (TSH) >2.5 µIU/ml in first trimester and TSH >3 µIU/ml in second trimester with normal free T4 (FT4) levels are included as cases. Controls are age, and trimester matched healthy first and second trimester singleton euthyroid pregnant women. Women with twinning, diabetes/impaired glucose tolerance, hypertension, prior history of thyroid disease or autoimmune disease, treatment for infertility, chronic infections, systemic illness, alcoholism, and smoking are excluded.
Figure 1: Study design. TPOAb +ve: Thyroid peroxidase antibody positive, TPOAb −ve: Thyroid peroxidase antibody negative

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Maternal serum samples are analyzed for TSH, FT4, and TPOAb using chemiluminescent method (Rosche, Elecsys, 2010, Hitachi High Technologies Corporation, Tokyo, Japan.). The normal ranges for TSH, FT4, and TPOAb are 0.1–2.5 µIU/ml in first trimester and 0.2–3 µIU/ml in second trimester, 0.82–1.8 ng/dl and ≤34 IU/ml, respectively. The lower limits of detection of these assays are 0.01 µIU/ml, 0.01 ng/dl, and 5 IU/ml, respectively. The interassay and intraassay coefficients of variation for all these assays are <10%.

SCH during pregnancy is defined by ATA as raised serum TSH but <10 µIU/ml (TSH >2.5 µIU/ml during the first trimester and >3.0 µIU/ml during the second and third trimesters) with normal serum FT4 levels. TPO antibodies are considered as positive if the titer was more than the upper limit of normal that is, 34 IU/ml. Cases are treated based on the recent ATA guidelines. The subjects are followed once in a month during their antenatal visits until delivery and then during delivery. All data concerning the pregnancy outcomes that is, miscarriage, pregnancy induced hypertension (PIH), placental abruption, gestational diabetes mellitus, PT delivery, cesarean section (CS) requirement, Apgar score, and low birth weight are recorded in follow-up.

The data are presented as mean ± standard deviation (SD) or percentage of cohort affected. The significance between means of two parameters is compared using the unpaired t-test. Standard error of the difference between proportions is used to find out the significance between two proportions. P < 0.05 is considered as statistically significant.


  Results Top


Of the hundred pregnant women recruited, 50 are SCH cases and the other 50 are euthyroid controls. [Table 1] outlines the baseline characteristics of the study group. TSH is higher in the SCH group ranging from 3.08 to 9.7 µIU/ml. When TSH is distributed into tertiles as 2.5–5 µIU/ml, 5.1–7.5 µIU/ml, and 7.6–10 µIU/ml; 72% of recruited SCH had TSH between 2.5 and 5 µIU/ml and 14% each in the other two tertiles. The mean (±SD) LT4 requirement among cases is 58.25 ± 19.82 µg with no significant difference in relation to TPOAb. Most of them became euthyroid within 2 months of starting LT4 therapy. TPOAb are positive in 27 (54%) cases and 30 (60%) controls. TPOAb positive women are older when compared to TPOAb negative women. More number of TPOAb positive subjects are multigravida among euthyroid women and primigravida in SCH.
Table 1: Baseline characteristics of cases and controls

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Pregnancy outcomes did not differ significantly between treated SCH and controls [Table 2]. There are also no significant differences in treated SCH women irrespective of TPOAb status [Table 3]. [Figure 2] outlines the pregnancy outcomes of treated SCH and TPOAb negative controls. PT deliveries (10% vs. 0) and the requirement of CS (36.73% vs. 15%) are significantly higher in SCH women when compared to TPOAb negative euthyroid women. [Figure 3] depicts the pregnancy outcomes of TPOAb positive and negative controls. PIH (6.67% vs. 0) is significantly higher in TPOAb positive controls when compared to TPOAb negative controls.
Table 2: Pregnancy outcomes in treated SCH versus controls

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Table 3: Pregnancy outcomes in treated SCH women based on TPOAb

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Figure 2: Pregnancy outcomes in treated subclinical hypothyroidism and thyroid peroxidase antibody negative euthyroid women. An asterisk indicates P < 0.05 for comparison between the groups. PIH: Pregnancy induced hypertension, GDM: Gestational diabetes mellitus, PT: Preterm, CS: Cesarean section, LBW: Low birth weight, SCH: Subclinical hypothyroidism, TPOAb: Thyroid peroxidase antibodies

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Figure 3: Pregnancy outcomes in thyroid peroxidase antibody positive and negative euthyroid women. An asterisk indicates P < 0.05 for comparison between the groups. PIH: Pregnancy induced hypertension, GDM: Gestational diabetes mellitus, PT: Preterm, CS: Cesarean section, LBW: Low birth weight, SCH: Subclinical hypothyroidism, TPOAb: Thyroid peroxidase antibodies

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  Discussion Top


The present study is aimed at assessing pregnancy outcomes in treated SCH compared to euthyroid women. There are no significant differences in pregnancy outcomes between treated SCH women and controls. Similarly, improvement in adverse pregnancy outcomes is described in the previous studies in treated SCH, especially by Negro et al.[2] Treatment of SCH women with LT4 based on the ATA guidelines might have led to the decline of adverse pregnancy outcomes.

Our study had a higher percentage of TPOAb positivity. TPO antibodies are positive in 54% of SCH women and 60% of euthyroid women. An Indian study by Gayathri et al. had shown the similar higher percentage of positive TPO antibodies in SCH (57.1%) but only 7% in euthyroid women.[6] Klein et al. showed that thyroid autoantibodies are found in 5–15% of women during childbearing age.[1] A higher positivity of TPO antibodies among euthyroid women in the current study could be a selection bias. The reasons are euthyroid women enrolled in this study had higher previous miscarriages, and they tested positive for TPOAb. Many of the euthyroid women in the current study were multigravida, which might also have contributed to the higher antibody positivity. The reason for this high degree of TPO antibodies needs further evaluation by future studies.

Women with SCH were treated and had similar pregnancy outcomes irrespective of their TPO antibody status. This is similar to the study by Jayaraman et al. who had studied pregnancy outcomes in relation to TPOAb status with an optimum LT4 replacement for SCH.[7] This could be due to the mitigation of antibody mediated effects by LT4 treatment. Thus, our study supports the importance of a TSH targeted approach during pregnancy.

SCH is further compared with TPOAb negative euthyroid women, and the results showed a significantly higher risk of PT deliveries and CS requirement among SCH women. Hence, this suggests that more number of TPO antibody positivity in controls might have attenuated the difference between cases and controls. In spite of adequate LT4 therapy, the significant difference in these obstetric outcomes could be due to late presentation to their first antenatal consultation.

Euthyroid women with positive TPOAb have higher adverse maternal outcomes especially PIH, which reached statistical significance compared to negative TPO antibodies. Studies by Feki et al.[8] and Mecacci et al.[9] had also shown a higher prevalence of PIH in TPOAb positive women. The other outcomes also would have been significant if the sample size was much bigger. The reason for adverse pregnancy outcomes could be, a thyroid with a reduced functional reserve, does not compensate for the pregnancy-related increased hormone requirement as suggested by Glinoer et al.[10] Thus, individuals with asymptomatic autoimmune thyroid disease who are euthyroid in early pregnancy carry a significant risk of developing hypothyroidism progressively during gestation.

The main limitations of the present study are small sample size and delay in initiation of LT4 therapy because of late reporting to antenatal clinics. We could not compare treated SCH women directly with the untreated SCH women, as it is unethical to avoid treatment for SCH women. The higher prevalence of TPO antibody positivity among euthyroid women in the current study should be confirmed with a larger sample size and epidemiological studies before generalizing to the entire population.

In summary, the present study concludes that SCH and thyroid autoimmunity influence pregnancy outcomes. Treatment with LT4 in SCH women is beneficial in decreasing adverse pregnancy outcomes. The presence of TPO antibodies in euthyroid pregnant women is also an alarming signal, where sequential monitoring throughout gestation would be beneficial.


  Conclusions Top


Adverse pregnancy outcomes are not significantly higher in treated SCH when compared to euthyroid women, and TPOAb status have not affected the outcomes in SCH. However, there are significantly higher PT deliveries and need for CS in SCH compared to TPOAb negative euthyroid women. Euthyroid women with TPOAb are associated with significantly higher risk of PIH.

 
  References Top

1.
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.  Back to cited text no. 1
    
2.
Negro R, Schwartz A, Gismondi R, Tinelli A, Mangieri T, Stagnaro-Green A. Universal screening versus case finding for detection and treatment of thyroid hormonal dysfunction during pregnancy. J Clin Endocrinol Metab 2010;95:1699-707.  Back to cited text no. 2
    
3.
Lazarus JH, Bestwick JP, Channon S, Paradice R, Maina A, Rees R, et al. Antenatal thyroid screening and childhood cognitive function. N Engl J Med 2012;366:493-501.  Back to cited text no. 3
    
4.
Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011;21:1081-125.  Back to cited text no. 4
    
5.
De Groot L, Abalovich M, Alexander EK, Amino N, Barbour L, Cobin RH, et al. Management of thyroid dysfunction during pregnancy and postpartum: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012;97:2543-65.  Back to cited text no. 5
    
6.
Gayathri R, Lavanya S, Raghavan K. Subclinical hypothyroidism and autoimmune thyroiditis in pregnancy – a study in south Indian subjects. J Assoc Physicians India 2009;57:691-3.  Back to cited text no. 6
    
7.
Jayaraman M, Verma A, Harikumar KV, Ugale M, Modi K. Pregnancy outcomes with thyroxine replacement for subclinical hypothyroidism: Role of thyroid autoimmunity. Indian J Endocrinol Metab 2013;17:294-7.  Back to cited text no. 7
    
8.
Feki M, Omar S, Menif O, Tanfous NB, Slimane H, Zouari F, et al. Thyroid disorders in pregnancy: Frequency and association with selected diseases and obstetrical complications in Tunisian women. Clin Biochem 2008;41:927-31.  Back to cited text no. 8
    
9.
Mecacci F, Parretti E, Cioni R, Lucchetti R, Magrini A, La Torre P, et al. Thyroid autoimmunity and its association with non-organ-specific antibodies and subclinical alterations of thyroid function in women with a history of pregnancy loss or preeclampsia. J Reprod Immunol 2000;46:39-50.  Back to cited text no. 9
    
10.
Glinoer D, Riahi M, Grün JP, Kinthaert J. Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metab 1994;79:197-204.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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Abstract
Introduction
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