Establishment of reference range for thyroid hormones in normal pregnant Indian women

Abstract

Background Interpretation of thyroid function tests during pregnancy needs trimester-related reference intervals from pregnant populations with minimal risk for thyroid dysfunction. While India has become iodine sufficient after two decades of salt iodisation, there is no normative data for thyroid function from healthy pregnant women of this country.Aims and objectives To determine trimester-specific reference ranges for free triiodothyronine (FT 3 ), free thyroxine (FT 4 ) and thyrotropin (TSH) from healthy pregnant Indian women.Design Cross-sectional study in a reference population of pregnant women.Setting Primary care level obstetric department in India.Population Women with uncomplicated pregnancy in any trimester.Methods Five hundred and forty-one apparently healthy pregnant women with uncomplicated single intrauterine gestations reporting to the Armed Forces Clinic in any trimester were consecutively recruited. Clinical examination, thyroid ultrasound for echogenicity and nodularity and estimation of FT 3 , FT 4 , TSH and antithyroid antibodies (antithyroperoxidase [anti-TPO] and antithyroglobulin [anti-Tg]) using electrochemiluminescence technique were carried out. From this entire sample, a disease-and risk-free reference population was obtained by excluding those with any known factor that could affect thyroid function or those who were being treated for thyroid dysfunction.Main outcome measure None.Results Of the 541 consecutive pregnant women in different trimesters enrolled for the study, 210 women were excluded. The composition of reference population comprising 331 women was 107 in first trimester, 137 in second trimester and 87 in third trimester. The 5th and 95th percentiles values were used to determine the reference ranges for FT 3 , FT 4 and TSH. The trimester-wise values in the first, second and third trimesters were: FT 3 (1.92-5.86, 3.2-5.73 and 3.3-5.18 pM/l), FT 4 (12-19.45, 9.48-19.58 and 11.32-17.7 pM/l) and TSH (0.6-5.0, 0.44-5.78 and 0.74-5.7 iu/ml), respectively. Analysis of mean, median values for FT 3 , FT 4 and TSH between each trimester showed no significant difference in FT 3 and TSH values (95% CI). However, FT 4 showed significant variation between trimesters with values decreasing with advancing gestational age (P value: first versus second = 0.015, first versus third = 0.003 and second versus third = not significant). Women with antibody positivity and hypoechogenicity of thyroid gland had significantly higher TSH values when compared with women with antibody negativity and normoechogenicity.Conclusions Reference ranges of FT 3 , FT 4 and TSH have been established for pregnant Indian women using 5th and 95th percentiles.

Recommendations on prenatal screening and the connections to other diseases such as thyroid dysfunction

“…Moreover, the use of different analytical systems could lead to a misdiagnosis, considering the differences among reference intervals for different analytical systems (80,84,87) .…”

11 Hypothyroidism in Pregnancy

“…Some researchers have established trimester-specific reference intervals for a local population ( The reference range for TSH is lower throughout pregnancy; both the lower normal limit and the upper normal limit of serum TSH are decreased by about 0.1-0.2 mIU/l and 1 mIU/l respectively, compared with the customary TSH reference interval of 0.4-4 mIU/l of non pregnant women. Serum TSH and its reference range rise gradually in the second and third trimesters, except for the study of Marwaha et al [84], but it is noteworthy that the TSH reference interval remains lower than in non pregnant women [80,81,85].…”

To study the neonatal outcomes in pregnancies with hypothyroidism in a tertiary referral centre

“…18 The large burden of subclinical hypothyroidism in pregnancy may prove to be a major public health burden in India, once it becomes clear that adverse outcomes can be corrected with screening and early replacement of levothyroxine. Children born to hypothyroid mothers have a poor intellectual function during the later part of their life.…”