Taiwanese Journal of Obstetrics & Gynecology 61 (2022) 960e964

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Taiwanese Journal of Obstetrics & Gynecology

journal homepage: www.tjog-online.com

Original Article

Does presence of subclinical hypothyroidism and thyroid auto

antibodies affect pregnancy outcomes in pregnancy? A record-based
cross-sectional study
Ülkü Ayşe Türker Aras a, *, Burcu Dinçgez b
a
Kafkas University, Department of Obstetrics and Gynecology, Şehitler Street No: 1, Kars, Turkey
b
Bursa Yuksek Ihtisas Training and Research Hospital, University of Health Sciences, Obstetrics and Gynecology, Emniyet Street No: 1, Bursa, Turkey

a r t i c l e i n f o a b s t r a c t

Article history: Objective: Our aim in this study is to determine the relationship between TPOAb positivity and preg-
Accepted 29 June 2022 nancy outcomes in the subclinical hypothyroid patient group.
Materials and methods: This study was started with 21,321 pregnant women, but after the exclusion
Keywords: criteria, 11,387 pregnant women were included int his study. Demographic characteristics of each patient
Subclinical hypothyroidism group included in the study, such as age, bodymass index (BMI), and laboratory parameters such as
Pregnancy
complete blood count (hemogram), liver and kidney function tests, type of delivery, birth weight,
Impaired glucose tolerance
neonatal intensive care admission, 1st and 5th minute APGAR scores, glucose tolerance test results,
Neonatal outcome
Maternal outcome
whether there was high blood pressure during pregnancy, whether there was premature rupture of
Thyroid auto antibodies membranes were recorded from the hospital information system and patient files.
Results: Pregnant women with subclinical hypothyroidism were divided into groups according to their
TPOAb status. When maternal and neonatal outcomes were evaluated between groups; Among these
four groups there was a statistically significant difference only in impaired glucose tolerance (IGT)
antibody groups with and without subclinical hypothyroidism according to their positivity (p < 0.01).
When the euthyroid TPOAb negative group was taken as reference, the risk of impaired and TPOAb
positive groups (OR: 1.210; 95% CI: 0.936e1.563; P ¼ 0.145), impaired in the group with subclinical
hypothyroidism but TPOAb positivity glucose tolerance 1.358(OR: 1.358); 95% CI: 1.042e1.770; P ¼ 0.023)
fold increased by 3.556 (OR: 3.556) in the group with subclinical hypothyroidism and TPOAb positivity;
(95% CI: 2.37e5.343; p < 0,001).
Conclusion: In ourstudy, there was a significant difference only in terms of IGT between the Groups with
and without subclinical hypothyroidism, depending on whether they were positive for TPOAb or not.
Therefore, studies in volving larger patient groups are needed.
© 2022 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction clear information about how to follow-up pregnant women with

SCH, whether treat them or not and pregnancy outcomes [2,3].
Subclinical hypothyroidism (SCH) is defined as a high serum Although a statistically significant difference was detected in terms
thyrotropin (TSH) level and a normal serum thyroxine (sT4) level of pregnancy outcomes between pregnant women with and
[1]. Hypothyroidism is defined a slow sT4 and elevated TSH levels. without SCH in some studies [5e16], no statistical differences were
Although SCH is detected in 1.5e42.9% during pregnancy, hypo- reported in some studies [4e7]. On the other hand, Thyroid auto-
thyroidism is detected in 0.4%. On the other hand, treating hypo- antibody positivity (TPOAb) is among the common causes of hy-
thyroidism during pregnancy has effects on maternal and fetal pothyroidism in women in there productive period. In some pre-
morbidity and mortality. For this reason, treatment is important [2]. vious studies, it was reported that TPOAb positivity affects
However, when the literature data were examined, there was no pregnancy outcomes [3]. The purpose of the present was to eval-
uate pregnancy outcomes according to TPOAb positivity and
negativity in the pregnant population with and without SCH.
* Corresponding author.
E-mail address: [email protected] (Ü.A. Türker Aras).

https://doi.org/10.1016/j.tjog.2022.06.013
1028-4559/© 2022 Taiwan Association of Obstetrics & Gynecology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
Ü.A. Türker Aras and B. Dinçgez Taiwanese Journal of Obstetrics & Gynecology 61 (2022) 960e964

Material and method Table 1

Definitions of variables: [30e36].

The region where the study was conducted Definition on variables

Loss of pregnancy Excretion of pregnancy material outside the

It was conducted in the obstetrics and gynecology department uterus before the 20th gestational week.
of a 3rd level health institution. Impaired Glucose Plasma glucoselevelis 100e126 mg/dL in fasting
Tolerance (IGT) measurement
Gestational Diabetes The 75-g oral glucose tolerance test was
Data source
Mellitus (GDM) performed. The presence of any of the following
diagnosis parameters in the measurements was
The data were obtained from the records of pregnant women considered as GDM:
who applied to the obstetrics and gynecology clinic of a 3rd level Fasting glucose  92 mg/dL
1st-hour glucose  180 mg/dL
hospital.
2nd-hour glucose  153 mg/dL
Pregnancy-Induced Blood pressure at or over 140/90 mmHg after
Study population Hypertension (HDP) the 20th gestational week
Decollement placenta The separation of the placenta from the uterine
The number of pregnant women who applied to the clinic in the cavity before labor occurs
Early Membrane The spontaneous separation of fetal membranes
first trimester and had TSH, sT4, whose TPOAb was checked be-
Rupture (EMR) before labor begins
tween December 2017 and applied, the study was continued with Placenta previa The placement of all or part of the placenta in
11,387 pregnant women. the lower uterine segment.
Preterm birth Labor occurs between the 24e37th weeks of
Exclusion criteria pregnancy
Low Birth Weight The fetus is less than 2500 g
(LBW)
Being younger than 18 years old, being older than 35 years, not NICU hospitalization Severe jaundice
continuing pregnancy follow-ups in our hospital, pregnancy not indications
being terminated in our hospital, absence of TSH, sT4, TPOAb data Births earlier than the 32nd gestational week
Respiratory distress
registered in our hospital system in the first trimester, first
Need for cardiorespiratory monitoring
trimester TSH > 10 mIU/L or TSH being <0.1 mIU/L, receiving Neonatal sepsis
treatment with thyroxine or anti thyroid drugs, pregnant women Conditions requiring exchange transfusion
with overt thyroid dysfunction, presence of any auto immune or
heart disease, history of diabetes mellitus and hypertensive disor-
der, multiple pregnancies, diagnosis of structural or genetic ab-
Statistical analysis
normality in the current pregnancy, liver or kidney failure, anemia
Statistical analyzes were made by using the SPSS statistical
(hemoglobin10 g/dL), any known thyroid disease in the past or a
software version 21.0 (Statistical Package for the Social Sciences).
family history of thyroid disease, drug use affecting thyroid func-
All data were reported as mean ± standard deviation, median
tions, uterine pathologies, history of recurrent pregnancy loss,
(minimum:maximum) values, or in percentages. Normal distribu-
preterm birth in previous pregnancies, history of placental abnor-
tion fit test was performed and an Anova test was used to compare
mality, and alcohol or smoking as addictive substance use.
the means. The Chi-Square. Test was performed to evaluate the
relationship between the categorical variables. Significant variables
Definitions of the laboratory measurements
were included in the Backward Logistics Regression Analysis
P < 0.05 was considered significant.
In all laboratory examinations, measurements were made from
fasting venous blood samples. Coulter LH780 Analyzer (Bechmen
Coulter Ireland, Inc.) was used for hematological measurements; Results
liver and kidney function tests were evaluated by using Abbott
Diagnostics C80002 (Abbott) Auto-Analyzer. Serum TSH, serums T4 In the present study, the rate of SCH was determined as 12.4%.
levels, and TPOAb were evaluated with Beckman Coulter DX1800 TPOAb positive SCH rate was 1.8%, TPOAb negative SCH rate was
electrochemilumnesence immunoassay. 10.5%, TPOAb positive euthyroid rate was 12.4%, and TPOAb nega-
tive euthyroid rate was 75.1%. TPOAb positivity was detected as
Variables of the study 14.4% in all pregnant women. The demographic and laboratory
parameters of the pregnant women are given in Table 1. In this
Dependent variables respect, no statistically significant differences were detected be-
Pregnancy outcomes. tween the groups in terms of age, BMI, HB, hematocrit (HTC),
platelet (PLT), aspartate amino transferase (AST), alanine amino
Independent variables transferase (ALT), and urea values (p ¼ 0.089; p ¼ 0.534; p ¼ 0.679;
Subclinical hypothyroidism accompanied by TPOAb positivity p ¼ 0.606; p ¼ 0.069; p ¼ 0.842; p ¼ 0.063; p ¼ 0.375 respectively).
(SCH þ abþ), subclinical hypothyroidism accompanied by TPOAb When the maternal results were evaluated, statistically signifi-
negativity (SCH þ ab), the euthyroid group accompanied by cant differences were detected between the independent variable
TPOAb positivity (SCH  abþ), and euthyroid group accompanied and, impaired glucose tolerance (IGT) (p ¼ 0.001), the dependent
by TPOAb negativity (SCH  ab). variable. No statistically significant differences were detected be-
Variable definitions are given in Table 1. tween pregnancy loss, GDM, high blood pressure during pregnancy,
placenta previa, abruption and delivery types (p ¼ 0.066, p ¼ 0.905,
Permission for the study p ¼ 0.262, p ¼ 0.051, p ¼ 0.943, p ¼ 0.514, respectively) (Table 2).
The study was conducted retrospectively (see Table 2). Approval On the other hand, when neonatal outcomes were examined, no
was obtained from the local ethics committee. The study was statistical differences were detected between the in dependent and
conducted in line with the declaration of Helsinki. dependent variables (NICU, APGAR<7, LBW, PROM, preterm birth)
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Ü.A. Türker Aras and B. Dinçgez Taiwanese Journal of Obstetrics & Gynecology 61 (2022) 960e964

Table 2
Distribution of the demographic and laboratory parameters between the study groups.

SCH () AB () SCH () AB (þ) SCH (þ) AB () SCH (þ) AB (þ) P

(n ¼ 8552) (n ¼ 1423) (n ¼ 1200) (n ¼ 212)

Age (years) 27.22 ± 4.47 27.51 ± 4.51 27.40 ± 4.44 27.08 ± 4.23 0.089
BMI (kg/m2) 25.08 ± 3.245 25.12 ± 3.29 25.22 ± 3.30 25.12 ± 3.14 0.534
HB (g/dl) 11.87 ± 2.12 11.94 ± 2.88 11.90 ± 3.07 11.79 ± 0.88 0.679
HTC (%) 35.95 ± 2.82 36.04 ± 2.91 35.92 ± 2.95 35.83 ± 2.86 0.606
PLT (*103/ml) 268.05 ± 62.12 264.93 ± 60.59 265.64 ± 59.48 260.22 ± 58.07 0.069
AST (IU/L) 18.96 ± 6.96 18.86 ± 6.75 19.03 ± 6.96 19.28 ± 7.14 0.842
ALT (IU/L) 14.72 ± 7.18 14.56 ± 6.83 15.18 ± 6.76 15.42 ± 6.80 0.063
Urea (mg/Dl) 7.49 ± 2.58 7.37 ± 2.73 7.45 ± 1.81 7.38 ± 1.90 0.375

a e SCH: Subclinical Hypothyroidism; b e TPOAb: thyroid antibody; c e n: number; d e BMI: Body Mass Index; e e HB: Hemogram; f e HTC: Hematocrit; g e PLT: Platelet; h e
ALT: Alanine aminotransferase; i e AST: Aspartate aminotransferase.

(p ¼ 0.763, p ¼ 0.564, p ¼ 0.391, p ¼ 0.159, p ¼ 0.993, respectively) Discussion

(Table 3).
When the study data were analyzed, it was determined that The frequency of thyroid diseases varies greatly. In the results of
only impaired glucose tolerance showed significant variability be- the previous studies conducted in the world. It is emphasized in
tween the groups. According to the Logistic Regression Analys is these studies that this variability occurs because of the presence of
results, when the euthyroid TPOAb negative group is taken as the regions where iodine deficiency is endemic [9]. There is a limitation
reference, the risk of impaired glucose tolerance in the euthyroid in comparing the data because the studies on SCH in pregnant
and TPOAb positive groups did not increase (OR: 1.210; 95% CI: women are so few that they can be counted with fingers (see
0.936e1.563), and the impaired glucose tolerance in the group with Table 5).
subclinical hypothyroidism but not TPOAb positivity was 1.358 (OR: In the present study, the frequency of SCH was found to be
1.358; 95% CI: 1.042e1.770) times, and 3.556 (OR: 3556; 95% CI: 12.4%. It was reported in a meta-analysis that the frequency of SCH
2.37e5343) times more in the group with subclinical hypothy- varied between 1.5% and 42.9% in pregnant women [1]. In a
roidism and TPOAb positivity (Table 4). hospital-based study conducted in Turkey, the frequency of SCH

Table 3
The distribution of the maternal outcomes between the study groups.

Pregnancy loss IGT GDM HDP P. Previa Decollement Birth type

No Yes No Yes No Yes No Yes No Yes No Yes No Yes

n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%)

SCH þ abþ 199 13 170 29 187 12 181 18 197 2 197 2 111 88

(93.9) (6.0) (85.4) (14.6) (94.0) (6.0) (91.0) (9.0) (99.0) (1.0) (99.0) (1.0) (55.8) (44.2)
SCH þ ab¡ 1128 72 1059 69 1060 68 1043 85 1119 9 1114 14 683 445
(94.0) (6.0) (93.9) (6.1) (94.0) (6.0) (92.5) (7.5) (99.2) (0.8) (98.8) (1.2) (65.3) (39.5)
SCH ¡ ABþ 1349 74 1276 73 1274 75 1259 90 1337 12 1331 18 818 531
(94.8) (5.2) (94.6) (5.4) (94.4) (5.6) (93.3) (6.7) (99.1) (0.9) (98.7) (1.3) (60.6) (39.4)
SCH ¡ ab¡ 8170 382 7796 374 7719 451 7646 524 8136 34 8056 114 4984 3186
(75.3) (70.6) (95.4) (4.61) (94.5) (5.5) (93.6) (6.4) (99.6) (0.4) (98.6) (1.4) (61.0) (39.0)
P 0.066 <0.001 0.905 0.262 0.051 0.943 0.514

a e SCH: Subclinical Hypothyroidism; b e TPOAb: thyroid autoantibody; c e n: number; d e IGT: Impaired Glucose Tolerance; e e GDM: gestational diabetes mellitus; f e HDP:
hypertensive disorders of pregnancy; g e P. Previa: placenta previa; h e LBW: Low birth weight; i e NICU; Newborn Intensive Care Unit; j e PROM: Preterm Membrane
Rupture; k e APGAR: Activity Pulse Grimace Appearance Respiration Score.

Table 4
The distribution of the neonatal results between the study groups.

NICU APGAR < 7 LBW EMR Preterm Birth

No Yes No Yes No Yes No Yes No Yes

n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%) n (%)

SCH þ abþ 191 (96.0) 8 (4.0) 190 (95.5) 9 (4.5) 179 (89.9) 20 (10.1) 182 (91.5) 17 (8.5) 190 (95.5) 9 (4.5)
SCH þ ab¡ 1084 (96.1) 44 (3.9) 1086 (96.3) 42 (3.7) 1052 (93.3) 75 (6.7) 1011 (89.6) 117 (10.4) 1081 (95.8) 47 (4.2)
SCH¡þ 1299 (96.3) 50 (3.7) 1297 (96.1) 52 (3.9) 1251 (92.7) 98 (7.3) 1223 (90.7) 126 (9.3) 1294 (95.9) 55 (4.1)
SCH ¡ ab¡ 7893 (96.6) 277 (3.4) 7899 (96.7) 271 (3.3) 7558 (92.6) 607 (7.4) 7479 (91.5) 691 (8.5) 7829 (95.8) 341 (4.2)
P 0.763 0.564 0.391 0.159 0.993

a e SCH: Subclinical Hypothyroidism; b e TPOAb: thyroid autoantibody; c e n: number; d e IGT: Impaired Glucose Tolerance; e e GDM: gestational diabetes mellitus; f e HDP:
hypertensive disorders of pregnancy; g e P. Previa: placenta previa; h e LBW: Low birth weight; i e NICU; Newborn Intensive Care Unit; j e PROM: Preterm Membrane
Rupture; k e APGAR: Activity Pulse Grimace Appearance Respiration Score.

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Table 5 levels of the patients in the range of 2.5e10 mIU/ml and the fT4
Logistic regression analysis results of the impaired glucose tolerance test. levels within the normal limits because the study was retrospective
Odds ratio 95 %CI Minemax P value and there were no local parameters for TSH [4].
SCH þ abþ 3.556 2.37e5.343 <0.001
As a conclusion, studies must be conducted to evaluate the
SCH þ ab¡ 1.358 1.042e1.770 0.023 pregnancy outcomes of subclinical hypothyroidism, including more
SCH ¡ abþ 1.210 0.936e1.563 0.145 patients and covering wider areas. Further studies must be con-
SCH ¡ ab¡ 1 (Reference Group) ducted to develop and use the diagnostic criteria for subclinical
a e SCH: Subclinical Hypothyroidism; b e TPOAb: Thyroid Autoantibody; c e CI: hypothyroidism all over the world.
Confidence Interval; d e OR: Odds Ratio.

Conflict of interest
was found to be 19.4% [10]. We believe that this difference in the
There is no conflict of interest among the researchers who
frequency of SCH occurred because these studies we reconducted in
participated in the study.
different regions [3,11]. On the other hand, TPOAb positivity was
found to be 14.4% in the study. When the studies in the literature
are examined, TPOAb positivity is found to be 10e20%, and this was Acknowledgments
found to be consistent with the result of the present study [12].
When the present study was evaluated in integrity, no statistically This study was not funded.
significant differences were detected between maternal and
neonatal outcomes (except IGT) as a result of the comparisons of
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