|Year : 2018 | Volume
| Issue : 2 | Page : 80-83
Effect of thyroid autoimmunity on pregnancy outcomes in gestational diabetes mellitus
Ramya Varada, Mythili Ayyagari, Vivekanand Bongi, Jayanthy Ramesh, K A V Subrahmanyam
Department of Endocrinology, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India
|Date of Web Publication||17-Jul-2018|
Department of Endocrinology, Andhra Medical College, Visakhapatnam, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Context: There are little data on the prevalence of thyroid autoimmunity in gestational diabetes mellitus (GDM) and its influence on pregnancy outcomes.
Aims: The aims were to estimate the prevalence of thyroid autoimmunity in euthyroid GDM and to compare the pregnancy outcomes in euthyroid antithyroid peroxidase antibody (TPOAb)-positive women to TPOAb-negative women and to compare the pregnancy outcomes across the euthyroid range of thyroid-stimulating hormone (TSH).
Design: This is an observational, prospective cohort study.
Subjects and Methods: One hundred women with GDM with euthyroid status were recruited. Samples were analyzed for TSH, free T4, and TPOAb. Women with TPOAb positivity were considered as cases and with TPOAb negativity were controls. Pregnancy outcomes assessed were pregnancy-induced hypertension (PIH), preterm delivery, cesarean section, birth weight, birth asphyxia, neonatal jaundice, hypoglycemia, seizures, and stillbirths.
Statistical Analysis: Student t-test and Chi-square test were used to compare the mean values between the groups and differences between proportions, respectively, and P < 0.05 was considered statistically significant.
Results: The prevalence of TPOAb positivity in euthyroid GDM was 14%. Pregnancy outcomes between cases and controls were similar except for neonatal jaundice (42.9% vs. 18.5%), which was statistically significant (P = 0.04). PIH occurred in 28.6% and 25.6% in cases and controls, respectively. There was no significant difference in maternal and neonatal outcomes across euthyroid range of TSH.
Conclusion: The prevalence of TPOAb positivity in euthyroid GDM was similar to the nondiabetic pregnant women. Neonatal jaundice was more in TPOAb-positive women. Pregnancy outcomes were comparable across the euthyroid range in GDM, suggesting similar range as those without GDM. There is no influence of thyroid autoimmunity on pregnancy outcomes in GDM in the present study.
Keywords: Gestational diabetes mellitus, pregnancy outcomes, thyroid autoimmunity
|How to cite this article:|
Varada R, Ayyagari M, Bongi V, Ramesh J, Subrahmanyam K A. Effect of thyroid autoimmunity on pregnancy outcomes in gestational diabetes mellitus. Thyroid Res Pract 2018;15:80-3
|How to cite this URL:|
Varada R, Ayyagari M, Bongi V, Ramesh J, Subrahmanyam K A. Effect of thyroid autoimmunity on pregnancy outcomes in gestational diabetes mellitus. Thyroid Res Pract [serial online] 2018 [cited 2018 Nov 22];15:80-3. Available from: http://www.thetrp.net/text.asp?2018/15/2/80/236703
| Introduction|| |
Gestational diabetes mellitus (GDM) and thyroid functional abnormalities are common disorders in pregnancy which can have adverse effects on pregnancy outcomes. 10%–15% of pregnant women have high titers of antithyroid peroxidase antibody (TPOAb) similar to general population. Several studies found a higher prevalence of thyroid autoimmunity in GDM and women with a history of GDM which speculated that gestational hyperglycemia may trigger thyroid autoimmunity.
In view of discrepancy of available studies, this study was designed to evaluate the prevalence of thyroid autoimmunity in pregnant women with GDM and the influence of it on pregnancy outcomes. The other objective was to compare the pregnancy outcomes across the euthyroid range in GDM mothers.
| Subjects and Methods|| |
This is an observational, prospective cohort study. The present study was done at the departments of endocrinology and obstetrics and gynecology in a South Indian tertiary care hospital from March 2015 to December 2016. One hundred singleton pregnant women aged >18 years with GDM between 24 and 28 weeks of gestation and euthyroid status were recruited for the study. Diagnosis of GDM was established as per the International Association of Diabetes and Pregnancy Study Groups criteria. Euthyroid status was defined as thyroid-stimulating hormone (TSH) between 0.3 and 3 μIU/ml.
TSH, FT4, and TPOAb were assayed using chemiluminescent method (Roche, ELECSYS 2010, Hitachi High-Technologies Corporation, Tokyo, Japan). The normal ranges for TSH, FT4, and TPO antibodies were 0.3–4.5 μIU/ml, 0.9–1.7 ng/ml, and ≤34 IU/ml, respectively. The inter- and intra-assay coefficient of variation for all these assays was <10%. Plasma glucose estimation was done by glucose oxidase–peroxidase method. TPOAb was considered positive if the titer was more than the upper limit of normal of the assay used, i.e., 34 IU/ml.
The women with positive TPOAb were considered as cases and those with negative TPOAb were considered as controls. They were followed once in a month during their antenatal visits until delivery and then until early neonatal period. Maternal outcomes analyzed were pregnancy-induced hypertension (PIH), preterm (PT) delivery (birth <37th gestational week), and cesarean section. Neonatal outcomes studied were birth weight, birth asphyxia, neonatal jaundice, hypoglycemia, seizures, and stillbirths.
The study was approved by the institutional ethics committee.
The data were presented as mean ± standard deviation or percentage of the cohort affected. Independent sample t-test was used for comparison of mean to calculate significance, and Chi-square test was used to calculate the difference between proportions. P < 0.05 was considered statistically significant.
| Results|| |
The prevalence of thyroid autoimmunity of 100 women with euthyroid GDM was 14%. All the baseline characteristics were similar between cases and controls [Table 1]. The mean TSH values were significantly higher in TPO-positive cases even within the euthyroid range (P< 0.05).
[Figure 1] shows the maternal outcomes in cases and controls, and PIH occurred in 28.6% and 25.6% in cases and controls, respectively (P = 0.81). None of the other outcomes reached statistical significance. [Table 2] shows the neonatal outcomes in cases and controls. Neonatal jaundice occurred in 42.9% and 18.5% in offspring of cases and controls, respectively (P = 0.04). There is no statistically significant difference between other outcomes. [Figure 2] shows the comparison of maternal outcomes within euthyroid range of TSH, by dividing individuals into two groups: Group 1 with TSH value of 0.2–2 μIU/ml and Group 2 with TSH of 2–3 μIU/ml. There was no significant difference in maternal outcomes between the two groups. [Table 3] shows that neonatal outcomes were comparable within two groups; however, there was a trend toward the increase in number of low-birth weight neonates in the group with TSH <2 μIU/ml.
|Figure 1: Maternal outcomes in cases and controls. PIH: Pregnancy-induced hypertension, PT: preterm, CS: Cesarean section|
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|Figure 2: Maternal outcomes across the euthyroid range. PIH: Pregnancy-induced hypertension, PT: Preterm, CS: Cesarean section|
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| Discussion|| |
The prevalence of thyroid autoimmunity in euthyroid GDM in our study was 14%, which was equal to the prevalence in general population and normal pregnant women.,, All the above-mentioned studies showed that TPOAb positivity in pregnant women was similar to general population, probably indicating that pregnancy does not have influence on thyroid autoimmunity.
Earlier studies from Italy done by Vitacolonna et al. and Olivieri et al. revealed a high prevalence of thyroid autoantibodies in pregnant women with GDM (17.6% and 16%, respectively)., Vitacolonna et al. further showed a higher TPOAb positivity of 26.2% in postpartum women with a history of GDM, possibly establishing the relationship between GDM and thyroid autoimmunity. In a study done in Iran, Shahbazian et al. found the prevalence of TPOAb in both GDM and normal pregnancies (27% and 23%, respectively), which is much higher than the prevalence in our study. In an Indian study, Gayathri et al. found the prevalence of 7% in euthyroid women without GDM. The present study has a prevalence of 14% in GDM. All the Western studies showed a similar prevalence comparable to our study. The discrepancy of prevalence of TPOAb in our study compared to the Indian study by Gayathri et al. could be explained by regional differences related to iodine sufficiency.
The present study showed a significantly higher TSH in cases compared to controls. However, there was no difference in the FT4 values between cases and controls. This discrepancy could be explained by the high prevalence of iodine deficiency in the baseline population; however, iodine deficiency was not analyzed in the participants. When comparison was done across the euthyroid range of TSH irrespective of TPOAb status, there was no significant difference between both maternal and fetal outcomes between these two groups. These results show that grades of TSH <3 μIU/ml do not have influence on pregnancy outcomes.
The maternal outcomes were similar in both cases and controls; there was slightly more PIH in TPOAb-positive women, but without statistical significance. In an Indian study by Chittamuri et al., positive TPOAb has higher adverse maternal outcomes, especially PIH (6.67% vs. 0) compared to negative TPOAb (P< 0.05). The prevalence of PIH in our study was high in both cases and controls (28.6% and 25.6%, respectively) with no significant difference, as the study population constitutes the GDM which itself is a risk factor for PIH. Our outcomes might have been significant if the sample size was much bigger. A study from Iran by Hossein-Nezhad showed the prevalence of 8% of PIH in GDM. Singh et al. from the All India Institute of Medical Sciences, New Delhi, reported the prevalence of 6.8% of PIH in GDM. Kumru et al.'s study showed no relationship between thyroid autoimmunity and PIH in contrast to the study by Saki et al. and Mecacci et al. which had shown a positive relationship between the presence of antibodies (anti-TPO and anti-thyroglobulin [Tg]) and preeclampsia.,, In Saki et al.'s study, thyroid autoimmunity increased the risk of PT delivery.
The prevalence of neonatal jaundice was significantly higher in TPOAb-positive women in the present study. However, TPOAb status did not influence the other neonatal outcomes. Kumru et al.'s study showed no increased risk of low birth weight and birth asphyxia with thyroid autoimmunity. Hence, probably, thyroid autoimmunity alone may not influence the neonatal outcomes; it is the thyroid dysfunction that has adverse effects on neonatal outcomes. There was no significant difference in pregnancy outcomes when analyzed across the euthyroid range of TSH, except for a trend toward the increase in the number of low-birth weight neonates in those with TSH <2 μIU/ml.
This is the first Indian study to observe the pregnancy outcomes in euthyroid GDM with and without TPOAb. The presence of TPO antibodies in euthyroid GDM did not have significant adverse pregnancy outcomes. There was no significant difference between the pregnancy outcomes across the euthyroid range of TSH, suggestive of TSH cutoffs similar to women without GDM.
The main limitation of the present study was small sample size. The pregnancy outcomes in euthyroid TPO antibody positive GDM women in the current study should be confirmed with a larger sample size and epidemiological studies before drawing more conclusions. Diagnosis of thyroid autoimmunity was based only on the detection of TPOAb. Anti-TgAb was not done in this study.
| Conclusion|| |
The prevalence of TPOAb positivity in euthyroid GDM was 14% in the present study. There was a trend toward the occurrence of PIH in TPOAb-positive women. Neonatal jaundice was significantly more in TPOAb-positive women. Pregnancy outcomes were comparable across the euthyroid TSH range in GDM, suggesting similar range as those without GDM. There is no influence of thyroid autoimmunity on pregnancy outcomes in GDM in the present study.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
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.
Vitacolonna E, Lapolla A, Di Nenno B, Passante A, Bucci I, Giuliani C, et al.
Gestational diabetes and thyroid autoimmunity. Int J Endocrinol 2012;2012:867415.
Mariotti S, Anelli S, Ruf J, Bechi R, Czarnocka B, Lombardi A, et al.
Comparison of serum thyroid microsomal and thyroid peroxidase autoantibodies in thyroid diseases. J Clin Endocrinol Metab 1987;65:987-93.
Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al
. American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2017;14:130-6.
Gupta A, Wajdi N, Verma A, Pal MK. Role of anti-thyroid peroxidase antibodies in adverse pregnancy outcomes Int J Reprod Contracept Obstet Gynecol 2016;5:3001-5.
Olivieri A, Valensise H, Magnani F, Medda E, De Angelis S, D'Archivio M, et al.
High frequency of antithyroid autoantibodies in pregnant women at increased risk of gestational diabetes mellitus. Eur J Endocrinol 2000;143:741-7.
Shahbazian H, Shahbazian N, Rahimi Baniani M, Yazdanpanah L, Latifi SM. Evaluation of thyroid dysfunction in pregnant women with gestational and pre-gestational diabetes. Pak J Med Sci 2013;29:638-41.
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.
Pandav CS, Yadav K, Srivastava R, Pandav R, Karmarkar MG. Iodine deficiency disorders (IDD) control in India. Indian J Med Res 2013;138:418-33.
] [Full text]
Chittamuri S, Bongi V, Ayyagari M, Kandregula DK, Subrahmanyam AV. Kandregula pregnancy outcomes in subclinicalhypothyroidism and thyroid autoimmunity. Thyroid Res Pract 2016;13:1-4. [Full text]
Hossein-Nezhad A. Comparison of incidence of pregnancy Induced hypertension in gestational diabetes mellitus and healthy pregnant women 2011. Iran J Diabetes Lipid Disord 2011;10:1-9.
Singh N, Madhu M, Vanamail P, Malik N, Kumar S. Efficacy of metformin in improving glycaemic control and perinatal outcome in gestational diabetes mellitus: A non-randomized study. Indian J Med Res 2017;145:623-8.
] [Full text]
Kumru P, Erdogdu E, Arisoy R, Demirci O, Ozkoral A, Ardic C, et al.
Effect of thyroid dysfunction and autoimmunity on pregnancy outcomes in low risk population. Arch Gynecol Obstet 2015;291:1047-54.
Saki F, Dabbaghmanesh MH, Ghaemi SZ, Forouhari S, Omrani GR, Bakhshayeshkaram M, et al.
Thyroid autoimmunity in pregnancy and its influences on maternal and fetal outcome in Iran (a prospective study). Endocr Res 2015;40:139-45.
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.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]