Distribution of thyroid peroxidase positivity and its effects on thyroid function in normal pregnant women during 1 st trimester in Dhaka city

Objective: To measure the distribution of TPO-Ab positivity and to observe the effect of thyroid peroxidase positivity on thyroid function during first trimester in normal pregnancy. Method: A cross sectional among 120 subjects were taken in this study and divided into control and study groups. Control group (Group A) consisted of 60 healthy non pregnant women age ranged between 20 to 35 years. Study group (Group B) consisted of 60 normal pregnant women of same age range. Group B was further subdivided into group B1 and group B2according to the level of TPO-Ab. Group B1 consisted of TPO-Ab positive pregnant women and group B2 consisted of TPOAb negative pregnant women. Control group was selected from personal contacts and study group from Out Patient Department (OPD) of Obstetrics and Gynecology of Sir Salimullah Medical College and Mitford Hospital. For assessment of thyroid function, serum free thyroxine (FT4), thyroid stimulating hormone (TSH) were measured. Serum FT4, TSH were measured by Enzyme link immunosorbant (ELISA) method. Again, serum TPO-Ab of total study population and hCG of all the pregnant women were measured. Serum TPOAb by Micro particle Enzyme Immunoassay (MEIA) method and hCG was estimated by ELISA. Statistical analysis was done by SPSS version 17. Results: In this study, serum FT4 and was significantly (P<0.001) higher and TSH level was significantly (P<0.001) lower in normal pregnant women during 1 trimester in comparison to those of non pregnant women. Again, 18% of pregnant women showed TPO-Ab positivity. However, serum FT4 level was significantly (P<0.001) lower whereas, TSH level was significantly (p<0.001) higher in TPO-Ab positive pregnant women in comparison to those of TPO-Ab negative pregnant women. Conclusion: TPO-Ab positivity increases during 1st trimester of normal pregnancy which decreases the hyper functional state of thyroid hormones. So, thyroid screening should be done routinely during pregnancy.


INTRODUCTION
During pregnancy various physiological and biochemical changes take place to meet the metabolic demand of the developing fetus 1 .Among the hormonal changes, thyroid *Address of Correspondence: Ohida Sultana, MBBS, M.phil(Physiology) Assistant Professor Kumudini Women's Medical College, Mirzapur.Bangladesh.Phone: +88-01818068886.
Updat Dent.Coll .j2014;4(1):15-20 hormone change is a remarkable one.The production, circulation and disposal of thyroid hormones are all altered during pregnancy 2 .Thyroid hormone is a calorigenic hormone which increases metabolic activities of almost all cells of the body and is essential for proper development of central nervous system 3 .First trimester of pregnancy which is up to 12 weeks of gestation is the most important period as organogenesis of fetus takes place at this stage .During 1 st trimester, the fetus completely depends on transplacental passage of maternal thyroxine, as fetal thyroid gland is non functional during this period 4 .So, normal thyroid function of mother during 1 st trimester is very important for fetal development 5 .Due to structural similarity with TSH and its high concentration, human chorionic gonadotropin (hCG) causes a transient increase in FT 4 level and decrease in TSH level during this period 6 .But, during pregnancy thyroid hypofunction may occur due to presence of thyroid peroxidase antibody (TPO-Ab) 7 .Thyroid peroxidase enzyme is a key enzyme in the formation of thyroid hormone, a major autoantigen in autoimmune thyroid disease.Thyroid peroxidase antibody (TPO-Ab) titer of 12 IU/ml or more is regarded as positive 8 .Pregnant women have a higher chance to develop thyroid autoantibodies specially thyroid peroxidase antibodies (TPO-Ab) in first trimester Usually, TPO-Ab positivity causes decrease in FT 4 level and increase in TSH level 9 .This altered thyroid function causes higher incidence of obstetrical complication 10 and negative pregnancy outcome such as miscarriage, prematurity, maternal post partum thyroiditis and post partum depression 11 .The rate of thyroid peroxidase antibody positivity is different in different countries.The rate of thyroid peroxidase antibody positivity is 11.2% among Pakistani pregnant women 12 , 11.7% in Italy 13 , (12-26) % in Netherlands 14 .So, TPO-Ab screening test can be an important routine diagnostic tool in early pregnancy which can help to identify women at risk for poor fetal outcome and post partum depression.But, little work is known on this regard in our country as well as in abroad.So, this study has been under taken which can provide a guideline to the obstetrician to take necessary step in euthyroid pregnant women with TPO-Ab positivity.

METHODS:
This cross sectional study was carried out in the Department of Physiology, Sir Salimullah Medical College and Mitford Hospital, Dhaka from January 2011 to December 2011.A total number of 120 euthyroid female subject's age ranged 20 To 35 years were included in this study.Among them sixty (60) were non-pregnant women (Group A) and another sixty (60) were primi gravid women (Group B) with gestational age between 9 to 12 weeks.This group was again subdivided in to group B 1 and B 2 according to the level of thyroid peroxidase antibody (TPO-Ab).Group B 1 Consisted of thyroid peroxidase antibody (TPO-Ab) positive pregnant women (TPO-Ab≥12IU/ml) and Group B 2 Consisted of thyroid peroxidase antibody (TPO-Ab) negative pregnant women (TPO Ab<12IU/ml).All the pregnant women were selected from Out Patient Department (OPD) of Obstetrics and Gynecology, Sir Salimullah Medical College and Mitford hospital and non-pregnant women were from personal contact by simple purposive sampling.All the subjects were belonged to middle socioeconomic status.Any subject suffering from systemic disease, endocrine abnormalities, user of drug that can affect thyroid function, smoking, alcoholism were excluded from the study.After selection of the subject the purpose, risks and benefits of the study was explained to each of the subject with a cordial attitude and only positive respondents were recruited as research participants.A written informed consents was taken from each participant.Detailed family and medical history were taken.Thorough physical examinations were done and all the informations were recorded in a prefixed questionnaire.Blood was collected for estimation of serum FT  The mean (±SD) serum TSH and TPO-Ab levels were significantly (p<0.001)higher, whereas, serum FT 4 level was significantly (p < 0.001) lower in group B 1 in comparison to those of group B 2. In contrast, serum hCG level was slightly higher in group B 1 in comparison to that of group B 2 but the difference was not statistically significant(Table lll).

DISCUSSION
The present study, serum free thyroxine (FT 4 ) level was significantly (p< 0.001) higher and TSH level was significantly (p<0.001)lower in normal pregnant women during 1 st trimester in comparison to those of non pregnant women.These findings are in consistent with the findings of some researchers. 15,16n the contrary, some other researchers had shown a lower level of serum FT 4 17 and higher level of serum TSH 18 in normal pregnant women during 1 st trimester in comparison to non pregnant women.18% of normal pregnant women during 1 st trimester had TPO-Ab positivity in this study whereas, this finding was different in other countries 19 .Serum free thyroxine (FT 4 ) level was significantly (p< 0.001) lower and TSH level was significantly (p<0.001) higher in TPO-Ab positive pregnant women during 1 st trimester in comparison to those of TPO-Ab negative pregnant women.Similar findings were also observed by some researchers. 20gain, serum hCG was slightly higher in TPO-Ab positive pregnant women in comparison to that of TPO-Ab negative women but the difference was not statistically significant.There are some postulated mechanisms suggested by various researchers of different countries which may imply the underlying causes regarding the changes in the present study.It has been suggested that, thyrotropic effect by higher concentration of serum hCG seems to be responsible for higher thyroid hormone concentration during 1st trimester 21 Increased fetal demand and increased placental transfer of thyroid hormone during pregnancy specially in 1 st trimester may also be responsible for the higher level of FT 4 indirectly by negative feedback mechanism 22 .Growing fetus release enough antigen to stimulate the maternal immune system which subsequently produce thyroid per oxidase antibodies and exerts inverse effect on maternal thyroid hormone synthesis 23 .Antibody against thyroid peroxidase enzyme (TPO-Ab) blocks each steps of thyroid hormone synthesis and causes a decrease in serum free thyroxine (FT 4 ) and increase in serum TSH levels in TPO-Ab positive women in comparison to those of TPO-Ab negative women during 1 st trimester 24 .
In the present study, mild hyper functional state of thyroid was observed in normal pregnant women during 1 st trimester as evidenced by higher level of serum FT4 and lower level of serum TSH in comparison to those of non pregnant women.This higher FT 4 level is most likely due to higher concentration of serum hCG during first trimester.The positive correlation of FT 4 with hCG is in favour of this suggestion.Again, lower TSH level is the result of negative feedback effect of FT 4 on TSH secretion.Moreover, thyroid peroxidase antibody positivity was present in 18% of pregnant women which indicates the raised autoimmune reaction during pregnancy.Although, serum hCG level was higher, serum FT 4 remained lower and TSH remained higher in TPO-Ab positive pregnant women in comparison to those of TPO-Ab negative pregnant women in this study may be due to competitive inhibition of hCG by higher level of TSH.

CONCLUSION:
The result of the study concludes that thyroid hyper functional state usually observed during 1 st trimesterin normal pregnancy, which may be due to 'thyrotrophic' effect of higher concentration of hCG during this period.This hyperfunctional state of thyroid gland can decrease in TPO-Ab positive pregnant women, which may cause pregnancy complications.So further study is required to observe the relationship of pregnancy related complication with TPO-Ab positivity.

Table I : Serum free thyroxine (FT 4 ), thyroid stimulating hormone (TSH) level in both groups (n=120)
4, TSH, TPO-Ab, hCG levels.Serum FT 4 , TSH and hCG were measured by Enzyme Link Immuno sorbent Assay (ELISA) in the laboratory of *** 0.000 *** Data are expressed as Mean ± SD.For statistical analysis, unpaired student's't' test was performed for comparison between the groups.Figure in parentheses indicate ranges.Group A: Apparently healthy non pregnant women (Control).Group B: Normal pregnant women during 1 st trimester (study).*** = Significant at p< 0.001 n= total number of subjects