Reference Ranges and Determinants of Thyroid Function and TSH Receptor Antibodies During Early Pregnancy in Nepal

Kjersti S Bakken; Apeksha Niraula; Ram K Chandyo; Manjeswori Ulak; Laxman Shrestha; Vijay Kumar Sharma; Tor A Strand; Tim I M Korevaar

doi:10.1111/cen.15175

Reference Ranges and Determinants of Thyroid Function and TSH Receptor Antibodies During Early Pregnancy in Nepal

Clin Endocrinol (Oxf). 2024 Dec 16. doi: 10.1111/cen.15175. Online ahead of print.

Authors

Kjersti S Bakken^{1

2}, Apeksha Niraula³, Ram K Chandyo⁴, Manjeswori Ulak^{1

5}, Laxman Shrestha⁵, Vijay Kumar Sharma³, Tor A Strand^{1

6}, Tim I M Korevaar⁷

Affiliations

¹ Center for International Health, University of Bergen, Bergen, Norway.
² Women's Clinic, Innlandet Hospital Trust, Lillehammer, Norway.
³ Department of Clinical Biochemistry, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal.
⁴ Department of Community Medicine, Kathmandu Medical College, Kathmandu, Nepal.
⁵ Department of Child Health, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal.
⁶ Department of Research, Innlandet Hospital Trust, Lillehammer, Norway.
⁷ Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.

PMID: 39676726
DOI: 10.1111/cen.15175

Abstract

Objective: Different definitions of thyroid dysfunction during pregnancy may lead to under or overtreatment. The aims of this study were to (1) define population-based pregnancy-specific reference ranges for thyroid dysfunction during early pregnancy in Nepal and assess the impact of antibody positivity, (2) quantify the diagnostic impact of population-based reference ranges compared with current practice and (3) assess the determinants of thyroid function and antibody positivity.

Methods: A total of 800 healthy pregnant women aged 20-40 years in the Bhaktapur municipality were included. Population-based reference ranges for thyroid hormones levels were defined as 2.5th and 97.5th percentiles using competitive immunoluminometric assay design. Thyroid disease cases and those with recommended treatment indications were calculated using current non-pregnancy new reference ranges. Multivariate regression analyses were performed to identify the determinants of thyroid hormones and antibody levels.

Results: Median gestational age was 11 weeks. The reference interval was 0.05-3.69 µLU/mL for thyroid stimulating hormone (TSH) and 8.89-15.28 pg/mL for free tetraiodothyronine (fT4) after excluding thyroid peroxidase antibody-positive women. Compared with the current non-pregnancy reference ranges, the new calculations increased the number of women who required treatment from 5 to 12 (0.9% increase). We identified 19 women (2.4%) who were positive for TSH receptor antibody (TRAb). We could not identify the determinants of TRAb positivity, and TRAb positivity was not associated with TSH or fT4 levels.

Conclusions: We found meaningful changes using population-based pregnancy-specific TSH and fT4 reference intervals and encourage further studies in other low- and middle-income settings. Our findings suggest that population screening for TRAb is not clinically meaningful.

Trial registration: Clinical Trial Registration: U1111-1183-4093.

Keywords: Nepal; TPOAb; TRAb; TgAb; pregnancy; reference range; thyroid autoimmunity; thyroid function.

Grants and funding

The study was supported by the Research Council of Norway through its Centres of Excellence scheme (project number 223269), the University of Bergen (UiB), Norway, to the Centre for Intervention Science in Maternal and Child Health (CISMAC), the Innlandet Hospital Trust (IHT) Research Fund (project number 150424), Lillehammer, Norway, Norges Forskningsråd, and Sykehuset Innlandet HF.