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Prevalance and fetomaternal outcome of thyroid disorder in pregnancy.

Introduction

Thyroid diseases are the commonest endocrine disorders affecting women of reproductive age group and hence constitute the commonest endocrine disorder in pregnancy also. It has long been recognized that maternal thyroid hormone excess or deficiency can influence the outcome for mother and fetus at all stages of pregnancy as well as interfere with ovulation and fertility. [1,2]

Maternal hypothyroidism is the most common disorder of thyroid function in pregnancy and has been associated with miscarriage, fetal loss, preeclampsia, preterm delivery, placental abruption, low birth weight, fetal distress and reduced intellectual function of the offspring. These adverse outcomes have been associated with both overt hypothyroidism found in about 0.2% of pregnancies as well as subclinical hypothyroidism found in about 2.3% of pregnancies. [3-6] Subclinical hyperthyroidism is found in 0.4% of pregnancies. [7] Maternal and fetal complications of hyperthyroidism include congestive heart failure, thyroid storm, hyperemesis gravidarum, preeclampsia, preterm delivery, fetal growth restriction, still birth, fetal and neonatal thyrotoxicosis. [8]

Autoimmune thyroid dysfunctions remain a common cause of both hyperthyroidism and hypothyroidism in pregnant women. Graves's disease accounts for more than 85% of all cases of hyperthyroid, whereas Hashimoto thyroiditis is the most common cause of hypothyroidism. Postpartum thyroiditis (PPT) reportedly affects 4-10% of women. PPT is an autoimmune thyroid disease that occurs during the first year after delivery. Usually it is manifested by 6 to 12 weeks postpartum. Women with PPT present with transient thyrotoxicosis, hypothyroidism, or transient thyrotoxicosis followed by hypothyroidism.

Thyroid dysfunction is often overlooked in pregnant women because of the nonspecific symptoms and the hyper metabolic state of pregnancy. [9] Hence thyroid function test becomes essential to know the thyroid status in pregnancy and also to detect the subclinical disease.

Materials and Methods

Source Area: Private hospital in Ahmedabad

Study Design: Observational Study.

Sampling Method: 100 Antenatal patients between 11-14 weeks of gestation undergoing Antenatal Care follow up at private hospital in Ahmedabad.

Inclusion Criteria: All pregnant women between 11-14 weeks of pregnancy.

Exclusion Criteria: (i) Multi-fetal gestation; (ii) Known chronic disorder like diabetes and hypertension; (iii) Previous bad obstetric history

Method: The present study was conducted on 100 ANC women after obtaining informed consent selected from private hospital in Ahmedabad. These women were followed from 11-14 weeks up to term. A detailed history was taken regarding the symptoms and sign of thyroid disorders which included Menstrual, Obstetric, Past, Medical, Family, Personal history. A through general physical examination in which Pulse, BP, Temperature, Respiratory rate was noted followed by CVS, CNS, RS, Local thyroid examination. Per abdomen and per vaginal examination was also done. Patient's blood samples were sent for TSH, FT3, FT4 levels. TSH level >2.5 [micro]U/ml then TPOAb was checked. In overt and subclinical hypothyroidism with or without TPOAb positive thyroxine dosage was titrated to maintain serum TSH <2.5 [micro]U/ml in first trimester and < 3 [micro]U/ml in second and third trimester. In overt hyperthyroidism PTU (propyl thiouracil) was given to the patient. Every 6-8 weekly TSH levels were estimated and the dose of drug adjusted accordingly. At the end, the obstetrical and perinatal outcome of pregnancy was noted. According to Marwaha et al. 2008 the following reference intervals for FT3, FT4 and TSH determined for each trimester of pregnancy are recommended for evaluation of thyroid status of pregnant Indian women.

American Thyroid Association 2011 recommended trimester-specific reference ranges for TSH are: (i) First trimester: 0.1-2.5 [micro]U/mL; (ii) Second trimester: 0.2-3.0 [micro]U/mL; (iii) Third trimester: 0.3-3.0 [micro]U/mL.

So in this study following first trimester reference ranges of FT3, FT4,TSH are taken.-TSH-0.1-2.5 [micro]U/mL, FT3-1.92-5.86 pmol/L, FT4-12-19.45 pmol/L (FT3, FT4 and serum TSH were done by chemiluminescence immunoassay method).

Overt Hypothyroidism: This includes women with a TSH concentration above the trimester-specific reference interval (>2.5 [micro]U/ml) with a decreased FT4 (<12 pmol/L) and FT3 (<1.92 pmol/L), and all women with a TSH concentration >10.0 ([micro]U/ml) irrespective of the level of FT4.

Subclinical Hypothyroidism: It is defined as a serum TSH between 2.5 and 10 ([micro]U/ml) with normal FT4 and FT3 concentration.

After confirming high TSH abnormality (TSH>2.5), TPOAb measurement is a necessity for establishing presence of thyroid autoimmunity as a cause of mild subclinical hypothyroidism. The development of thyroid failure considered when higher concentration of TPOAb is present.

Increased levels of TPOAb is associated with (normal level TPO Ab-0 to 40) increased pregnancy failure rates, increased incidence of gestational thyroid dysfunction and pre-disposition to post-partum thyroiditis.

Hyperthyroidism: It is defined when TSH is low (<0.1 [micro]U/ml) and FT4 (>19.45 pmol/L) or FT3 (>5.86 pmol) is high.

Subclinical Hyperthyroidism: It occurs when FT4 (>19.45 pmol/L) or FT3 (>5.86 pmol) is high and TSH normal (0.1-2.5 [micro]U/ml).

Results

Overt or inadequately treated hypothyroidism is a risk factor of miscarriage and possibly preterm birth and fetal death. This study showed that in patients having overt hypothyroidism 50% (1/2) had IUD, 100% (2/2) developed preeclampsia, 100% (2/2) presented with preterm labour and 50% (1/2) had abruption.

Maximum numbers of patients were in 21-25 years (52%) age group. This was the age group of peak reproductive period. Table 4 shows that out of 5 patients with positive TPOAb, 3 developed preeclampsia, 4 underwent LSCS out of which 2 were preterm, 2 patients developed postpartum thyroiditis, 4 babies develop neonatal jaundice. All above complications were much lower in patients with negative TPOAb.

Discussion

On the basis of the results of this study, combined with those reported in the literature, some recommendations can be drawn. Gestational age specific reference ranges are of utmost importance because 8% of the patients would be missed for the diagnosis of subclinical hypothyroidism in this study. By gestational age specific reference intervals clinicians can reliably evaluate thyroid function and monitor thyroxine replacement therapy in pregnant women.

Overt or inadequately treated hypothyroidism is a risk factor of miscarriage and possibly preterm birth and fetal death (Abalovich et al. 2002, Allan et al. 2000). [4,20] This study showed that in overt hypothyroidism woman 50% (1/2) had IUD, 100% (2/2) developed preeclampsia, 100% (2/2) had preterm labour, 50% (1/2) had abruption. Another main previous finding is that the offspring of mothers with hypothyroidism have adverse neuropsychological outcome (Haddow et al. 1999) Pop et al. 2003, Henrichs et al. 2010). [6,20] Our results also show that mothers with TPOAb positive (50%), with hypothyroidism and subclinical hypothyroidism during pregnancy, have a very high incidence of subsequent thyroid disease, which would warrant routine check-up of these women later in their lives.

These findings indicate that adequate treatment of those with known hypothyroidism and reorganization of those at risk of progressing to overt hypothyroidism during pregnancy is to be recommended--preferably before pregnancy. It is recommended that those with overt hyperthyroidism, as defined by the new trimester-specific reference intervals, are treated and closely monitored, as the need for antithyroid therapy typically decreases as pregnancy progresses. The first few weeks of pregnancy are the most important time for brain development in the fetus and even subtle T4 deficiency in the mother may lead to poorer neuropsychological outcome.

Conclusion

By gestational age specific reference intervals clinicians can reliably evaluate thyroid function and monitor thyroxine replacement therapy in pregnant women. TPOAb positive are associated with an increased risk of abortion and these infants are more often born preterm. TSH is the hallmark in detection of hypothyroid as well hyperthyroid so TSH should be included in the list of routine investigations done in all antenatal women in first trimester. If TSH values are abnormal then FT3, FT4 and TPOAb need to be checked.

References

[1.] Casey BM, Leveno KJ. Thyroid disease in pregnancy. Obstet Gynecol 2006;108:1283-92.

[2.] Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd EW, Leveno KJ, et al. Subclinical Hypothyroidism and pregnancy outcomes. Obstet Gynecol 2005;105:239-45.

[3.] Abalovich M, Gutierrex S, Alcaraz G, Maccallini G, Garcia A, Levalle O. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid 2002;12:63-68.

[4.] Negro R, Formoso G, Mangieri T, Pezzarossa A, Sazzi D, Hassan H. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab 2006;91:2587-91.

[5.] Mestman JH. Hyperthyroidism in pregnancy. Endocrinol Metab Clin North Am 1998;27:127-49. doi:10.1016/S0889 8529(05)70303-0

[6.] Le Bean SO, Mandal SJ. Thyroid disorders during pregnancy. Endocrinal Metab Clin N Am 2006;35:117-36.

[7.] Ganong WF. The thyroid gland. In: Ganong WF, (edi). Review of Medical Physiology, 22nd ed. New York: Lange medical Books/McGraw-Hill; 2005. p. 317-32.

[8.] Hadley ME, Levine JE. Thyroid hormones. In: Endocrinology, 6th edi. Upper Saddle River, NJ: Pearson Prentice Hall, 2007. p. 293-314.

[9.] Valimaki M, Schalin-Jantti C. Kilpirauhanen. In: Valimaki M, Sane T, Dunkel L, (eds). Endokrinologia. Helsinki: Kustannus Oy Duodecim.; 2009. p. 174-230.

[10.] Anselmo J, Cao D, Karrison T, Weiss RE, Refetoff S. Fetal loss associated with excess thyroid hormone exposure. JAMA 2004;292:691-5.

[11.] Oken E, Braverman LE, Platek D, Mitchell ML, Lee SL, Pearce EN. Neonatal thyroxine, maternal thyroid function, and child cognition. J Clin Endocrinol Metab 2009;94:497-503.

[12.] Sullivan M. Antenatal Thyroid Screen Does Not Boost Child's IQ. Clinical Endocrinology News. 2010;5:16-7.

[13.] Delahunty C, Falconer S, Hume R, Jackson L, Midgley P, Mirfield M, et al. Levels of neonatal thyroid hormone in preterm infants and neurodevelopmental outcome at 5 1/2 years: millennium cohort study. J Clin Endocrinol Metab 2010;95:4898-908.

[14.] Lee RH, Spencer CA, Mestman JH, Miller EA, Petrovic I, Braverman LE, et al. Free T4 immunoassays are flawed during pregnancy. Am J Obstet Gynecol 2009;200:260 e1-6.

[15.] Anckaert E, Poppe K, Van Uytfanghe K, Schiettecatte J, Foulon W, Thienpont LM. FT4 immunoassays may display a pattern during pregnancy similar to the equilibrium dialysis ID-LC/tandem MS candidate reference measurement procedure in spite of susceptibility towards binding protein alterations. Clin Chim Acta 2010:411:1348-53.

[16.] Yue B, Rockwood AL, Sandrock T, La'ulu SL, Kushnir MM, Meikle AW. Free thyroid hormones in serum by direct equilibrium dialysis and online solid-phase extraction--liquid chromatography/tandem mass spectrometry. Clin Chem 2008;54:642-51.

[17.] Fister P, Gaberscek S, Zaletel K, Krhin B, Hojker S, Gersak K. Thyroid function in the third trimester of pregnancy and after delivery in an area of adequate iodine intake. Int J Gynaecol Obstet 2010;112:52-5.

[18.] Klajnbard A, Szecsi PB, Colov NP, Andersen MR, Jorgensen M, Bjorngaard B, et al. Laboratory reference intervals during pregnancy, delivery and the early postpartum period. Clin Chem Lab Med 2010;48:237-48.

[19.] Costeira MJ, Oliveira P, Ares S, Roque S, de Escobar GM, Palha JA. Parameters of thyroid function throughout and after pregnancy in an iodine-deficient population. Thyroid 2010;20(9):995-1001.

[20.] Ashoor G, Maiz N, Rotas M, Kametas NA, Nicolaides KH. Maternal thyroid function at 11 to 13 weeks of gestation and subsequent development of preeclampsia. Prenat Diagn 2010;30:1032-8.

Rajita S Jani (1), Devangi S Munshi (1), Shashwat K Jani (2), Sanjay P Munshi (2), Smit B Solanki (2), Viral M Pandya (2)

(1) Department of Obstetrics and Gynaecology, AMC MET Medical College, LG Hospital, Ahmedabad, Gujarat, India

(2) Department of Obstetrics and Gynaecology, Smt. NHL Municipal Medical College, VS General Hospital, Ahmedabad, Gujarat, India

Correspondence to: Rajita S Jani (rajita.munshi@gmail.com)

DOI: 10.5455/ijmsph.2014.260520143

Received Date: 15.04.2014

Accepted Date: 26.05.2014
Table-1: Pregnancy and thyroid related hormones

Hormones                          Trimester

                       First        Second        Third

FT3 (pmol/L)         1.92-5.86     3.2-5.73      3.3-5.18
FT4 (pmol/L)          12-19.45    9.48-19.58   11.32-17.70
TSH ([micro]U/ml)     0.6-5.0     0.44-5.78     0.74-5.70

Table-2: Characteristics of the Patients

                           Characteristics                   N     %

                                18-20                       23    23
Age Group                       21-25                       52    52
(years)                         26-30                       20    20
                                31-35                       05     5
Parity                       Primigravida                   32    32
             Multigravida with previous viable pregnancy    56    56
               Multigravida with previous abortion (s)      12    12
Thyroid                       Euthyroid                     87    87
Status                       Hyperthyroid                    1     1
                       Subclinical hyperthyroid              2     2
                             Hypothyroid                     2     2
                       Subclinical hypothyroid               8     8

Table-3: TSH level & maternal and fetal outcome

                                            TSH ([micro]U/ml)

                                      < 0.1    0.1-2.5    2.6-5

                 No. of cases           1        89         6

Maternal       FTND (> 37 weeks)        0        39         3
               LSCS (> 37 weeks)        0        33         1
                VD (< 37 weeks)         0         8         0
               LSCS (< 37 weeks)        1         5         1
            Hyperemesis gravidarum      1         4         0
                 Preeclampsia           1        12         1
                   Abruption            0         2         1
                      IUD               0         2         0
                   Abortion             0         4         1
             Postpartum thyroditis      0        NA         1
Fetal                 LBW               1        19         2
              Congenital anomaly        0         3         0
                   Jaundice             1        43         4

                                          TSH ([micro]U/ml)

                                      5.1-7.5   7.6-10    > 10

                 No. of cases            2        1        1

Maternal       FTND (> 37 weeks)         0        0        0
               LSCS (> 37 weeks)         1        0        0
                VD (< 37 weeks)          0        0        1
               LSCS (< 37 weeks)         0        1        0
            Hyperemesis gravidarum       0        0        0
                 Preeclampsia            1        1        1
                   Abruption             0        0        1
                      IUD                0        0        1
                   Abortion              1        0        0
             Postpartum thyroditis       0        1        0
Fetal                 LBW                0        1        0
              Congenital anomaly         0        0        0
                   Jaundice              1        1        0

Table-4: Thyroid peroxidase Antibody (TPOAb) & maternal and
fetal outcome

                                               TPOAb

                                      Positive    Negative

                 No. of cases             5           5

Maternal       FTND (> 37 weeks)          0           3
               LSCS (> 37 weeks)          2           0
                VD (< 37 weeks)           0           1
               LSCS (< 37 weeks)          2           0
            Hyperemesis gravidarum        0           0
                 Preeclampsia             3           1
                   Abruption              1           1
                      IUD                 0           1
                   Abortion               1           1
             Postpartum thyroditis        2           0
Fetal                 LBW                 3           0
              Congenital anomaly          0           0
                   Jaundice               4           2

Table-5: Thyroid status & maternal and fetal outcome

Maternal or fetal                       Thyroid status
complication
                           Euthyroid     Hyperthyroid     Subclinical
                                                         Hyperthyroid

Hyperemesis gravidarum     3 (3.44%)       1 (100%)         1 (50%)
  (N=5)
Preeclampsia (N=17)       11 (12.64%)      1 (100%)         1 (50%)
Preterm delivery (N=17)   13 (14.95%)      1 (100%)            0
Abruptio (N=4)             2 (2.30%)           0               0
Abortion (N=6)             4 (4.60%)           0               0
IUD (N=3)                  2 (2.30%)           0               0
Fetal distress (N=15)     11 (12.65%)          0            1 (50%)
Neonatal jaundice         42 (48.27%)      1 (100%)         1 (50%)
  (N=51)

Maternal or fetal                 Thyroid status
complication
                          Hypothyroid    Subclinical
                                         Hypothyroid

Hyperemesis gravidarum         0              0
  (N=5)
Preeclampsia (N=17)         2 (100%)       2 (25%)
Preterm delivery (N=17)     1 (50%)       1 (12.50%)
Abruptio (N=4)              1 (50%)       1 (12.50%)
Abortion (N=6)                 0           2 (25%)
IUD (N=3)                   1 (50%)           0
Fetal distress (N=15)       1 (50%)        2 (25%)
Neonatal jaundice           1 (50%)        6 (75%)
  (N=51)
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Title Annotation:RESEARCH ARTICLE
Author:Jani, Rajita S.; Munshi, Devangi S.; Jani, Shashwat K.; Munshi, Sanjay P.; Solanki, Smit B.; Pandya,
Publication:International Journal of Medical Science and Public Health
Article Type:Report
Geographic Code:9INDI
Date:Aug 1, 2014
Words:2457
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