Subclinical hypothyroidism in pregnancy – assessment of offspring thyroid status and mitochondrial robustness to stress

Abstract

Subclinical hypothyroidism’s clinical implications on pregnancy are controversial. Consequently, thyrotropin (TSH) cutoff-values for pregnancy are continuously a subject for debate. In subclinical hypothyroidism, altered levels of thyroid hormones may affect mitochondrial function.

Objectives were i) to analyze thyroid hormone levels in offspring of women with and without subclinical hypothyroidism ii) to analyze mitochondrial “robustness” in terms of MTG/TMRM ratio in pregnant women and their offspring in relation to thyroid function and iii) to perform differentiate analyses on different TSH thresholds to determine the importance of cutoff-values to results.

Pregnant women were included by blood collections prior to a planned cesarean section, and cord samples were collected after delivery. Thyroid status (analyzed by Siemens Healthcare Diagnostics by an electrochemical luminescent immunoassay based on LOCI-technology) grouped the women and their offspring in euthyroid or subclinical hypothyroid, with groups established from previous recommended third-trimester cutoff-value (TSH > 3.0 mIU/L) and the recently recommended cutoff-value in Denmark (TSH > 3.7 mIU/L). Flow cytometric measurements of mitochondrial function in mononuclear blood cells with the fluorophores TetraMethylRhodamine Methyl Ester (TMRM) and Mitotracker Green (MTG) were used to evaluate mitochondrial robustness as the MTG/TMRM ratio.

No significant differences in mitochondrial robustness between euthyroid and subclinical hypothyroid cohorts were observed, irrespective of TSH-cutoff applied. Maternal and cord MTG/TMRM ratios were positively correlated. Cord-TSH was elevated in subclinical hypothyroid offspring, independent of TSH cutoff applied. Cord-TSH was associated with maternal TSH-level, maternal smoking and cord arterial-pH.

Keywords:

• Mitochondria
• thyroid diseases
• pregnancy
• flow cytometry
• thyrotropin
• infant
• newborn
• subclinical hypothyroidism
• reference levels

Acknowledgements

The authors would like to thank technicians Jette Ellehauge and Carina Foldager at the Department of Clinical Biochemistry, Naestved Hospital, Region Zealand, for their dedicated work. Moreover, Professor Jan Kvetny for inspiration and launching of the project, and Jane Clements for English proofreading.

Ethics approval

The study was approved by the Regional Ethics Committee of Zealand (SJ-361), and by the Danish Data Protection Agency. The study conformed to the Declaration of Helsinki. The study was registered in Clinical Trials (NCT02061111). All adult participants received oral and written information, and both parents had to accept the inclusion of the child in the study by written consent.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The study was supported by grants from Region Zealand’s Medical Research Foundation, the Medical Research Foundation of Naestved, Slagelse and Ringsted Hospitals, Region Zealand, and the Dept. of Gynecology and Obstetrics, Naestved/Slagelse Hospital, to which we are grateful.