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. 2024 Mar 4;13(2):e230163.
doi: 10.1530/ETJ-23-0163. Print 2024 Apr 1.

Hypothyroxinaemia during gestation is associated with low ferritin and increased levels of inflammatory markers

Victor J M Pop  1 , Johannes G Krabbe  2 , Maarten Broeren  3 , Wilmar Wiersinga  4 , Margaret P Rayman  5
Affiliations

Hypothyroxinaemia during gestation is associated with low ferritin and increased levels of inflammatory markers

Victor J M Pop et al. Eur Thyroid J. .

Abstract

Objective: Pregnancy is a state of physiological inflammation facilitating implantation. Early isolated hypothyroxinaemia (IH) and increased inflammation (including obesity) have been associated with severe obstetric complications. The current study evaluated the association between IH, low ferritin and inflammation parameters (interleukin 6 (IL-6), C-reactive protein (CRP), human chorionic gonadotrophin (hCG) and obesity. Moreover, the course of these parameters throughout pregnancy was evaluated in relation to IH.

Methods: In the cross-sectional study (A) at 12 weeks, 2759 women participated and 2433 participated in the longitudinal study (B) with assessments at 12, 20 and 28 weeks gestation. At the first trimester, 122 (4.4%) IH women (free thyroxine (FT4) <5th percentile, normal TSH levels) were compared with 2114 (76.6%) reference women (FT4 between tenth and 90th percentiles, normal thyrotrophin (TSH) levels), in study B these figures were 99 (4.1%) and 1847 (75.9%), respectively.

Results: Cross-sectionally, compared to reference women, IH was independently associated with low ferritin (<5th percentile, OR: 2.6, 95% CI: 1.4-4.9), high CRP (>95th percentile: OR: 1.9, 95% CI: 1.04-3.7), low hCG (<median, OR: 2.1, 95% CI: 1.40-3.16), obesity (BMI > 30, OR: 1.7, 95% CI: 1.12.9) and higher age (OR: 1.1, 95% CI: 1.04-1.15). Longitudinally, compared to reference women, women with IH at 12 weeks gestation showed persistently and significantly lower ferritin and hCG levels, and persistently higher CRP and IL-6 levels throughout gestation.

Conclusion: Gestational IH could be viewed as a condition of increased inflammation, as reported in non-thyroidal illness syndrome. Less favourable inflammation parameters and low iron status during early gestation in IH women seem to persist throughout gestation.

Keywords: inflammation; isolated hypothyroxinaemia; pregnancy.

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Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the study reported.

Figures

Figure 1
Figure 1
Flow chart of pregnant women of the Brabant Study who were included in the cross-sectional and the longitudinal follow-up study.
Figure 2
Figure 2
Number of cases (%) with low ferritin (<5th percentile), high CRP and high IL-6 (>95th percentile), low hCG (below median) and high BMI (>30) of 122 women with isolated hypothyroxinaemia (FT4 <5th percentile with TSH between 2.5th and 97.5th percentiles) compared with the number of cases of the 2114 women of the reference group (FT4 between tenth and 90th percentile with TSH between 2.5th and 97.5th percentile) at 12 weeks gestation. P refers to chi-square tests: df = 1.
Figure 3
Figure 3
Mean concentrations of FT4 (A) and mean log(TSH) (B) throughout gestation of 99 women with IH (isolated hypothyroxinaemia) compared to 1847 women with adequate FT4 levels (between tenth and 90th percentiles) at 12 weeks gestation.
Figure 4
Figure 4
Comparison between 99 IH women and 1847 women with adequate FT4 levels (FT4 between tenth and 90th percentiles) at 12 weeks gestation with regard to: mean (log)CRP, (A); mean (log)IL-6, (B); mean (log)fer, (C); mean (log)hCG, (D), throughout gestation. The left Y-axis shows mean log concentrations, the right Y-axis shows the corresponding linear concentrations. IH: isolated hypothyroxinaemia.
See this image and copyright information in PMC

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