Pregnancy represents a challenge to the maternal thyroid gland: the various hormonal variations and the increased metabolic demands occurring during ge-station deeply affect thyroid function [1]. The most common cause of gestational hypothyroidism is auto-immune. In a subset of mothers with autoimmune hypothyroidism, thyroid-stimulating hormone (TSH) blocking antibodies can be transferred to the fetus and cause either transient hyperthyrotropinemia or even hypothyroidism in the neonatal period requiring medications in some affected newborns [2]. Thyroid hormones (TH) play an indispensable role in vertebrate embryogenesis, fetal development and maturation. Serum thyroid-stimulating hormone (TSH) remains the primary screening test for thyroid dysfunction. and Evaluation of thyroid hormone replacement therapy in patients with primary hypothyroidism.

During early pregnancy, before the development of a functioning thyroid gland, the fetus is dependent on TH supplied by the mother Maternal hypothyroidism has been associated with poor pregnancy outcome, decreased birth weight and impaired neuropsy-chological development of the offspring [3].

During pregnancy, resistance to thyroid hormone beta (RTH β) serves as a unique model of isolated fetal hyperthyroidism, since the wild-type (WT) fetus is exposed to excessive levels of TH while the mother remains in a clinically eumetabolic state.

Furthermore, the absence of thyroid stimulating antibodies precludes the possibility of autoaimmunity affecting the fetus’ thyroid status [4]. Variations in serum TSH can occur physiologically in pregnancy. During the first trimester, serum TSH usually becomes lower, but rarely decreases to less than 0.1 mU/L, owing to the stimulatory effects of human chorionic gonado-tropin on the thyroid. Serum TSH subsequently returns to normal in the second trimester [5, 6].

Thyroid stimulation starts as early as the first trimester by β-human chorionic gonadotrophin (HCG) hormone, which shares some structural homology with thyroid-stimulating hormone. There is also an estrogen-mediated increase in circulating levels of thyroid-binding globulin (TBG) during pregnancy by 2∼3 times in serum TBG concentrations [7].

Thyroid function tests during first-trimester of pregnancy and particularly the reference interval for thyroid function tests for pregnant women in each region has to be established, to prevent mis-diagnosis and irreversible mental and physical adverse affect for growing fetus [8].

The incidence of varicella is low in pregnant women. The risk of viral pneumonia is not increased, but varicella zoaster virus (VZV)–associated pneumonia is usually more severe in pregnant women. Approximately 90% of women of childbearing age are immune to varicella because this disease is a common childhood illness and the vaccination against VZV has spread in many countries [9].

Rubella easily crosses the placenta of infected pregnant women; in the first trimester, rubella causes miscarriage or fetal death, or congenital rubella syndrome (CRS) could develop. CRS includes auditory, sensorineural, cardiac and ocular abnormalities. In cases in which the primary rubella infection occurs during the first 4  months of pregnancy, a prenatal diagnosis of fetal infection could be proposed. Some infections such as cytomegalovirus (CMV), rubella and toxoplasmosis may result in serious complications in the fetus and the newborn. In a healthy adult, these infections may be asymptomatic or result in mild symptoms. However, depending on gestational age, transplacental infection may cause problems ranging from long-term sequenced to intrauterine or neonatal death.

Investigating changes in exposure to various infectious agents during pregnancy is important in terms of reflecting the health status of the mother and the fetus. Screening for thyroid dysfunction is recom-mended among certain groups of women, who plan a pregnancy. Management of thyroid disease during pregnancy requires special consideration because pregnancy induces major changes in thyroid function, and maternal thyroid disease can have adverse affects on the pregnancy and the fetus. The purpose of this study was to investigate the correlation between thyroid-related factors and infectious factors among prenatal tests of normal pregnant women.

1. Subjects

This study was a retrospective study conducted on data from the normal pregnancy women in Bundang CHA women hospital, which is the most recent data that measured. The thyroid related factors and congenital infection factors were determined using standard laboratory techniques on a Cobas^Ⓡ8000 modular analyzer (Roche Diagnostic International AG, Rotkreuz, Switzerland) by particle enhanced immuno-turbidimetric assay). These data were a cross-sectional survey conducted by outpatients in Bundang CHA women hospital. These were performed from June 2016 to December 2016. Among the 2033 subjects who participated in the outpatients. However, since the test items were variously performed from the same patient, there was a missing value in the analysis. This study has been conducted according to the principles expressed in the Declaration of Helsinki (approved and exemp-tion by Institutional Review Board No. 1041479-201705-HR-009 at N. University).

2. General characteristics

Patients were excluded if they had received abortion, Most of the attendants were missing a test result according to the condition of pregnancy and the request for additional test items for antenatal testing. Results items from normal pregnant women, thyroid-stimulating hormone (TSH), triiodothyronine (T3), free thyroxine (FT4), Varicella zoster virus (VZA) IgM/G, Rubella IgM/G, human immunodeficiency virus (HIV), Hepatitis C virus (HCV) and hepatitis B virus (HBs) Ag/Ab. and general characteristic was pregnancy duration and fetus type (single, twin).

3. Statistical analysis

The level of statistical significance was defined as having a P-value of less than 0.05 or 0.01. Data were analyzed using PASW version 17.0 (SPSS Inc., Chicago, IL, USA). Categorical variables were reported as per-centages and compared using the chi-square or Fisher’s exact test as appropriate. The results of TSH, T3 and FT4 will be calculated as mean and standard deviation.

Calculate mistakes and percentages for the results of infected persons VZA, Rubella, HCV, HBs. and Analysis of VZA, rubella, HCV and HBs factors according to the distribution of TSH, T3 and FT4. Correlation between TSH, T3 and FT4 were analyzed by Pearson correlation coefficient.

1. Distribution of general characteristics parameters in clinical patients

The frequency of general characteristics of the participants are shown in Table 1. Most of 493 subjects (66.6%) were over the age of 30∼39 years. The VZV IgG (93.3%) and rubella IgG (89.8%) was mostly detected to positive and VZV IgM (96.4%) and rubella IgM (99.4%) was mostly detected to negative. The HIV was detected to negative in all patients. Among them quantitative analysis. mostly negative was 0.1∼0.2 ng/mL amount. The HCV was almostly negative (99.5%). HBs Ag was distribute to positive (2.9%), over 0.3 ng/mL of negative (95.5%). The positive of HBsAb was abudantly detected (76.3%) but negative detected (23.7%). Mostly patients was included in 11∼12 weeks pregnancy and fetus type was single. For thyroid related factors were mostly normal range included (Table 1).

Table 1

Frequency of general characteristics in the study participants

Characteristic	Variables	N	%
Age (years)	<19	6	0.8
	20∼29	107	14.5
	30∼39	493	66.6
	40∼49	112	15.1
	50∼59	22	3.0
VZV IgG	Equivocal	5	3.0
	Negative	6	3.7
	Positive	153	93.3
VZV IgM	Equivocal	4	2.4
	Negative	159	96.4
	Positive	2	1.2
Rubella IgG	Equivocal	33	7.0
	Negative	15	3.2
	Positive	423	89.8
Rubella IgM	Equivocal	1	0.2
	Negative	467	99.4
	Positive	2	0.4
HIV (ng/mL)	Negative	339	100.02
	<0.1	10	9
	0.1∼0.2	259	76.4
	0.2∼0.3	62	18.3
	>0.3	8	2.4
	Positive	0	0
HCV Ab (ng/mL)	Negative	381	99.5
	<0.1	371	96.9
	0.1∼0.2	4	1.0
	0.2∼0.3	1	0.3
	>0.3	5	1.3
	Positive	2	0.5
HBs Ag (ng/mL)	Negative	381	97.1
	<0.3	6	1.6
	>0.3	365	95.5
	Positive	11	2.9
HBs Ab (ng/mL)	Negative	381	23.7
	<2.0	70	20.0
	2∼10	13	3.7
	Positive	267	76.3
Pregnancy weeks	11	92	37.6
	12	108	44.1
	13	13	5.3
	14	11	4.5
	15∼16	14	5.7
	>17	7	2.9
Fetus type	Single	229	93.5
	Twin	16	6.5
T3 (0.6∼1.8 ng/mL)	Normal	140	97.9
	Abnormal	3	2.1
	Mean±SD	1.09±0.28
TSH (0.35∼5.5 μIU/mL)	Normal	468	98.3
	Abnormal	8	1.7
	Mean±SD	1.59±1.47
FT4 (0.89∼1.76 ng/dL)	Normal	334	97.1
	Abnormal	10	2.9
	Mean±SD	1.19±0.27

Abbreviations: VZA, varicella zoster virus; HIV, human immunodeficiency virus; HCV, hepatitis C virus; HBs, hepatitis B virus; TSH, thyroid-stimulating hormone; T3, triiodothyronine; FT4, free thyroxine.

2. The comparison of infection factors according to thyroid related factors

The age-related changes in T3 showed a tendency to decrease with age (P<0.001). VZV and rubella were not statistically significant. In HIV, FT4 was negative but increased 0.2∼0.3 compared with 0.1∼0.2 groups. The results of HCV showed a statistically significant increase in T3 in the positive group compared to the negative group of 0∼0.2. However, there was no significant difference in HBs and gestational age, but FT4 was statistically significantly higher in fetuses with twins (Table 2).

Table 2

Mean score of thyroid related factors according parameters (N=127)

Variables	Mean±SD
	T3	TSH	FT4	Schéffe
Age (years)	1.0±0.28	1.5±1.47	1.1±0.27
<19		2.0±1.01	1.2±0.07
20∼29a	1.1±0.43	1.5±1.49	1.2±0.33	a>b
30∼39	1.1±0.31	1.4±1.37	1.1±0.27
40∼49	1.0±0.22	1.9±1.76	1.1±0.29
50∼59b	0.9±0.17	1.8±1.26	1.1±0.27
F (P) value	3.915 (0.010)	2.208 (0.067)	0.567 (0.687)
VZV IgG	1.3±0.35	1.3±1.11	1.2±0.26
Equivocal		0.6±0.27	1.2±0.01
Negative		1.3±0.54	1.1±0.23
Positive	1.3±0.35	1.3±1.13	1.2±0.26
F (P) value		1.061 (0.349)	0.252 (0.778)
VZV IgM	1.4±0.35	1.3±1.11	1.2±0.26
Equivocal		1.1±0.95	1.2±0.01
Negative	1.4±0.35	1.3±1.10	1.2±0.01
Positive		1.8±2.48	0.9±0.17
F (P) value		0.264 (0.768)	0.057 (0.945)
Rubella IgG	1.1±0.33	1.4±1.38	1.1±0.22
Equivocal	1.0±0.29	1.1±0.78	1.1±0.13
Negative	1.0±0.01	1.3±1.03	1.2±0.16
Positive	1.2±0.33	1.5±1.43	1.1±0.23
F (P) value	0.818 (0.449)	0.535 (0.587)	0.521 (0.595)
Rubella IgM	1.1±0.33	1.4±1.37	1.1±0.22
Equivocal
Negative	1.1±0.32	1.4±1.38	1.1±0.22
Positive	0.7±0.01	1.0±0.14	1.1±0.02
F (P) value	1.562 (0.219)	0.223 (0.630)	0.080 (0.778)
HIV	1.0±0.27	1.6±1.55	1.1±0.22
Negative
<0.1	0.9±0.13	1.4±1.00	1.0±0.19	a<b
0.1∼0.2a	1.1±0.26	1.7±1.63	1.1±0.21
0.2∼0.3b	1.0±0.32	1.4±1.35	1.2±0.23
>0.3	1.0±0.14	2.3±0.94	1.0±0.21
Positive
F (P) value	0.795 (0.499)	1.291 (0.277)	5.257 (0.002)
HCV Ab	1.0±0.26	1.6±1.52	1.1±0.23
Negative
<0.1	1.0±0.25	1.6±1.52	1.1±0.23	a<b
0.1∼0.2a	0.8±0.09	1.5±1.53	1.3±0.27
0.2∼0.3	1.4±0.01	2.3±0.01	1.2±0.01
>0.3	1.5±0.01	1.4±1.45	1.0±0.18
Positiveb	1.7±0.01	0.1±0.09	1.4±0.01
F (P) value	3.232 (0.015)	0.558 (0.693)	0.802 (0.525)
HBs Ag	1.0±0.27	1.7±1.58	1.1±0.25
Negative
<0.3	0.9±0.13	1.3±1.22	1.1±0.04
>0.3	1.0±0.28	1.7±1.60	1.1±0.26
Positive	1.0±0.18	1.1±0.75	1.1±0.12
F (P) value	0.279 (0.757)	0.911 (0.403)	0.277 (0.758)
HBs Ab	1.0±0.26	1.7±1.60	1.1±0.22
Negative
<2.0	1.0±0.19	1.9±2.06	1.1±0.18
2∼10	0.9±0.12	1.4±0.92	1.1±0.13
Positive	1.1±0.27	1.7±1.47	1.1±0.24
F (P) value	0.911 (0.405)	1.155 (0.316)	1.155 (0.317)
Pregnancy weeks	1.3±0.32	1.2±1.17	1.2±0.27
11	1.3±0.33	1.3±1.03	1.2±0.22
12	1.2±0.37	1.3±1.43	1.2±0.35
13	1.2±0.01	1.1±0.50	1.1±0.12
14	1.5±0.14	1.3±0.79	1.0±0.10
15∼16		0.7±0.54	1.1±0.21
>17		1.4±1.01	1.0±0.06
F (P) value	0.393 (0.760)	0.601 (0.699)	1.088 (0.415)
Fetal	1.3±0.32	1.2±1.17	1.2±0.27	a<b
Singlea	1.3±0.32	1.3±1.20	1.1±0.22
Twinb	1.4±0.27	1.0±0.66	1.4±0.71
F (P) value	0.690 (0.415)	0.947 (0.331)	6.169 (0.014)

Abbreviation: See Table 1.

3. Correlation of T3 and TSH according to FT4 status

The reference values of FT4 were divided into normal group and abnormal group. As a result of cross-analysis between normal and abnormal group based on the reference values of T3 and TSH, The correlation between FT4 and T3 was statistically significant, but TSH was not statistically significant with FT4 (P<0.05) (Table 3).

Table 3

Mean score of parameters according to FT4 levels status (Mean±SD)

Variables	Free thyroxine		χ2 (P) value
	Normal (N=34)	Abnormal (N=93)
T3 (ng/mL)	1.0±0.27	1.4±0.60
Normal	N=138	N=2	45.974 (0.001)*
Abnormal	N=1	N=2
TSH (μIU/mL)	1.7±0.03	1.6±0.06
Normal	N=325	N=10	0.246 (0.620)
Abnormal	N=8	-

Abbreviation: See Table 1.

*P<0.05.

4. Infection factors according to tertile of TSH

The results of TSH were divided into tertile, and the correlation between each infection factor and general characteristics was investigated. In the age distribution, the highest distribution and TSH value were statistically significant (P<0.05) in 30∼39 years old group. Also, HIV-negative group was higher in the concentration of 0.1∼0.2, Statistically significant (P<0.05). However, the association with other infectious agents was not statistically significant (Table 4).

Table 4

Difference of parameters in according to the levels of TSH

Variables	Total	Q∼.30a (N=143)	Q.31∼.70b (N=190)	Q.71∼c (N=143)	χ2	P
Age					15.690	0.047
<19	5	0	2	3
20∼29	54	16	24	14
30∼39	300	104	117	79
40∼49	95	19	37	39
50∼59	22	4	10	8
VZV IgG					5.281	0.260
Equivocal	5	4	1	0
Negative	6	1	3	2
Positive	142	52	59	31
VZV IgM					3.875	0.423
Equivocal	3	2	0	1
Negative	149	55	63	31
Positive	2	1	0	1
Rubella IgG					2.022	0.732
Equivocal	15	5	8	2
Negative	10	2	6	2
Positive	184	57	81	46
Rubella IgM					2.402	0.301
Negative	206	64	93	49
Positive	2	0	2	0
HIV					12.824	0.046
Negative
<0.1	10	5	2	3
0.1∼0.2a	247	68	96	83
0.2∼0.3b	62	18	32	12
>0.3	8	0	3	5
Positive	0	0	0	0
HCV Ab					11.764	0.162
Negative
<0.1	359	96	149	114
0.1∼0.2a	4	1	2	1
0.2∼0.3	1	0	0	1
>0.3	5	3	0	2
Positiveb	2	2	0	0
HBS Ag					2.349	0.672
Negative	6	2	3	1
<0.3	355	90	140	125
>0.3	11	4	5	2
Positive
HBS Ab					2.699	0.609
Negative	68	19	22	27
<2.0	12	3	6	3
2∼10	230	62	109	89
Positive
Pregnancy weeks					8.903	0.541
11	88	31	34	23
12	101	38	41	22
13	12	4	7	1
14	11	3	6	2
15∼16	12	7	4	1
>17	7	3	1	3
Fetal					0.078	0.962
Singlea	216	80	87	49
Twinb	15	6	6	3

Abbreviation: See Table 1.

5. Difference of thyroid related factors according to thirds percentile with TSH

The correlations of the thyroid-related factors according to tertile of TSH. the T3, TSH and FT4 were found to be correlated. Especially, TSH values were statistically significant according to low group, middle group, and high group, and T3 and FT4 were statistically lower than those of low group. On the other hand, T3 and FT4 showed opposite results with TSH between groups (Table 5).

Table 5

Thyroid related factors in according to the third grade of TSH levels (Mean±SD)

Variables	Total	Q∼.30a (N=143)	Q.31∼.70b (N=190)	Q.71∼c (N=143)	F (P)	Schéffe* (P)
T3 (ng/mL)	1.09±0.28 (143)	1.21±0.35 (36)	1.06±0.23 (59)	1.04±0.26 (48)	4.638 (0.011)	a>c, b>c
FT4 (ng/dL)	1.19±0.27 (343)	1.34±0.40 (143)	1.16±0.17 (190)	1.11±0.17 (143)	21.539 (0.001)	a>c, b<c
TSH (μIU/mL)	1.59±1.47 (476)	0.41±0.24 (92)	1.25±0.29 (137)	3.22±1.69 (114)	326.675 (0.001)	a<b<c

Abbreviation: See Table 1.

*P<0.05.

6. Correlation of thyroid related factors

Table 6 showed the significant correlation between thyroid factors. The T3 and FT4 factors showed a significant positive correlation. but TSH showed a significant negative correlation with T3, FT4 values.

Table 6

Correlation of thyroid factors (r(P))

	T3	TSH	FT4
T3	1
TSH	−0.194* (0.020)	1
FT4	0.247** (0.003)	−0.276** (0.000)	1

Abbreviation: See Table 1.

**P<0.01, *P<0.05.

This study was a retrospective study that investigated the correlation between the prevalence of thyroid factor and prenatal infection in normal pregnant women. Pregnancy-related changes in thyroid phy-si-ology lead to changes in the thyroid function tests. Therefore, parameters of healthy pregnant women differ from those of euthyroid non-pregnant women. The trimester specific range for TSH, as defined in populations with optimal iodine intake, need to be applied while the interpretation of FT4 values necessitates trimester and method-specific ranges given a significant method-dependent variation in the FT4 measurement in pregnancy. Thyroid function in pregnancy and the TSH in pregnancy is physiologically lower than the non-pregnant population [10].

Early diagnosis for thyroid dysfunction of pregnant women and treatment of thyroid dysfunction during pregnancy is important and cost effective to avoid both fetal and maternal complications secondary to thyroid dysfunction [11]. Thyroid function testing during the neonatal period can be fraught with difficulty in interpretation due to the larger variation of normal levels and an overlap between TSH surge and patho-logical levels. These difficulties are compounded by differences in newborn screening methods in different laboratories. Infants with maternal history of thyroid disease may require additional testing beyond the newborn screen. However, providers can consider delaying test until after thyroid levels are more stable [12].

Low thyroid hormone levels during pregnancy have also been associated with impaired fetal neurological development [13]. Trimester-specific ranges for serum TSH as set by each different laboratory should be used in pregnancy. If not available, the following upper limits of normal range are recommended: TSH 2.5 mIU/L for the first trimester, 3.0 mIU/L for the second trimester, and 3.5 mIU/L for the third trimester [5]. Total T4 increases during the first trimester of pregnancy and the reference range is approximately 1.5-fold that of the nonpregnant range throughout the pregnancy [14].

Pregnant mother and infant protection is a priority in the health because these population groups are mostly exposed to the diseases and death. Thyroid dysfunction is one of the common complications of pregnancy and it contributes significantly to the maternal and fetus morbidity and mortality. Neonates born from mothers who developed varicella between D-5 and D+2 of delivery should also receive as soon as possible specific anti-VZV immunoglobulins [15]. Varicella immunization is recommended for all non-immune women as part of pre-pregnancy and postpartum care and Varicella vaccination should not be administered in pregnancy. However, termination of pregnancy should not be advised because of inadvertent vaccination during pregnancy.

The CMV and toxoplasma infections. We assessed IgG and IgM antibodies in pregnant women applying to the hospital in the first trimester and IgG avidity was utilized as a supplemental test to exclude acute infection and prevent unnecessary intervention. Since women had no serological status tested prior to pregnancy, we were not able to assess seroconversion of IgG antibodies. Thus, only women with elevated IgM antibody titers together with high IgG titers were further evaluated with avidity test to diagnose or exclude primary infection [16].

The trend for a correlation between high titers of CMV DNA in breast milk at 6 months and CMV infection at 6 months (P=0.069). In this cohort, more than 95 % of the children had acquired CMV infection by 2 years of age. Besides breastfeeding, which played a major role, also horizontal transmission between 1 and 2 years was certainly relevant in determining CMV infection ac-quisition [17]. The delivery route does not change the risk of maternal-fetal transmission of hepatitis B when serovaccination at birth was well conducted. Likewise, breast feeding does not change the risk of maternal-fetal transmission of hepatitis B after serovaccination [18].

Therefore, it is thought that it is important to evaluate the identification of various infectious persons to the prenatal pregnant women through this study, and it can be understood that the metabolic ability of the mother reflects the health condition of the fetus because it is a factor that directly affects the fetus. Also, monitoring the changes of various thyroid factors according to the exposure status of the infected person presented in this study may play an important role in antenatal screening.

In conclusion, this study may help to understand the pathophysiological mechanisms of infectious agents and sensory pathogens. Pregnancy represents a challenge to the maternal thyroid gland: the various hormonal variations and the increased metabolic demands occurring during gestation deeply affect thyroid function [19, 20]. Adequate thyroid hormone availability is important for an uncomplicated pregnancy and optimal fetal growth and development. Here, we put studies from the past decade on reference ranges for TSH, determinants of thyroid dysfunction, risks of adverse outcomes and options for treatment into perspective. In addition, we provide an overview of the current views on thyroid physiology during pregnancy and discuss strategies appropriate diagnosis, care and management of thyroid dysfunction in the pre-pregnancy, pregnancy and post-pregnancy periods are important to minimize the risk of complications, long-term effects of the mother and fetus.

임신은 갑상선 기능 검사의 중요한 해석을 필요로 하며 임신 중 갑상선 기능 이상과 외부 바이러스성 감염 인자들의 항체의 존재는 태아 및 산모의 건강에 영향을 미치기에 임신에서 갑상선 기능의 선별적 평가가 요구된다. 본 연구에서는 임신기간 동안 정상 산모들의 선택적 산전 감염인자 검사 항목 중에서 갑상선 관련 인자와 바이러스성 감염 인자의 임신시기별 상호 연관성을 알아보고자 하는 후향적 단편 실태조사이다. 분석한 결과를 살펴보면, T3는 나이가 증가함에 따라 감소하고, 특히 HCV가 양성인 그룹에서 양의 유의성을 보였다(P<0.01). 또한 HIV가 음성이지만 임계치에 근접하거나 쌍둥이 임산부에서는 FT4가 유의한 증가를 나타냈다(P<0.05). TSH는 30대 연령에서 높게 분포하였으며, 다른 바이러스성 감염인자와는 통계적 유의성이 나타나지 않았다. 또한, TSH의 결과 값을 삼분위로 나누어 분석한 결과, FT4와 T3은 양의 상관성을 보였으나 TSH와는 음의 상관성을 보였다(P<0.05). 따라서 본 연구를 통해서 임신 중 산전검사인 갑상선 검사와 바이러스성 감염인자의 검사를 통한 임신 중 평가는 임신 경과시간, 감염인자의 노출상태 및 정량적 수치의 상태를 반영하여 이루어져야 할 것이며, 갑상선 관련 내분비 인자에 대한 산전검사의 유용성에 대한 평가의 보완이 이루어져야 할 것으로 사료된다.

None

None

Lim DK^1,2, M.T., graduate student; Park CE³, Professor.