Global and Indian perspectives on trimester-specific reference intervals for thyroid hormones in pregnant women: a systematic review

Establishment of trimester-specific reference intervals (RIs) for thyroid hormones is essential to avoid misdiagnosis and misinterpretation in pregnant women. This systematic review comprehensively analysed gestational age-specific reference intervals in different populations. The electronic databases such as Medline, Embase, Scopus, and Google Scholar were searched to identify relevant articles. The reference population, consisting of healthy pregnant women in the first, second, and third trimesters of pregnancy, meeting eligibility, such as the absence of thyroid disease, a negative thyroid peroxidase (TPO) antibody test, and sufficient urinary iodine concentration (UIC), was selected for the present study. Of the 1,160 studies identified in the databases, 48 were eligible for the systematic review. Data on trimester-specific RIs, established from a 95% confidence interval (CI) between the 2.5th percentile (lower limit) and the 97.5th percentile (upper limit) of thyroid hormones, were extracted. In most studies, the upper limit of TSH in healthy pregnant women during the first (85.4%), second (94.1%), and third trimesters (72%) was determined to be 2.15–4.51 mIU/L, 2.73–4.84 mIU/L, and 2.90–4.91 mIU/L, respectively. Furthermore, the lower and upper limits of FT4 during the first (80.5% and 87.8%), second (83.3% and 90%), and third trimesters (82.1% and 96.4%) have been reported as being between 10.17 and 14.16 pmol/L and 15.22–23.94 pmol/L, 8.31–11.71 pmol/L and 15.47–20.59 pmol/L, and 7.39–9.78 pmol/L and 12.03–19.82 pmol/L, respectively. The study results showed that reference value for thyroid hormones vary within the same population and also between different populations, particularly for TSH. Given this high variability, even within the Indian population, it is imperative to establish population-specific reference values. This systematic review examined trimester-specific reference intervals for thyroid hormones in women with a naturally conceived singleton pregnancy, normal iodine intake, negative TPO Abs, and a gestation-specific RI based on the 2.5th and 97.5th percentiles, with an emphasis on global and Indian perspectives. Half of the included studies reported additional exclusion criteria in addition to the primary criteria such as multiple foetuses, conception by IVF and known thyroid diseases. As the pregnancy progresses, TSH reference intervals increase over the trimesters, while FT4 reference values decrease. Pregnancy specific- reference Intervals for thyroid hormones vary considerably among Indian women, therefore it is necessary to establish population-specific RIs in India.