Endocrine Abstracts

Background: Normal pregnancy is a state of physiological oxidative stress (OS) with oxidants facilitating the implantation of the embryo and optimal decidualisation but counterbalanced by antioxidants. Pro-oxidant processes exceeding the anti-oxidants capacity result in imbalanced OS, which has been associated with the ‘’big four’’ obstetric complications: pre-term birth, intra-uterine growth retardation, pre-eclampsia and diabetes gravidarum. Important OS balance modulators are TH, hCG, CRP, the cytokine IL-6 and the iron status, often reflected by the serum ferritin level.

Rationale of the study: Early gestational hypothyroxinaemia has also repeatedly been associated with poor obstetric outcome and with impaired offspring neurodevelopment. Non-thyroidal illness has been conceptualized as a model of impaired balance of OS due to inflammation.

Aim of the study: In an area with sufficient iodine intake, to evaluate the possible association between 1^st trimester hypothyroxinemia and the different parameters involved in OS including ferritin, IL-6, CRP, and hCG, adjusting for age and parity.

Methods: Between June 2018 and December 2022, the Brabant Study (BrSt) recruited 2835 pregnant women. We defined hypothyroxinaemia as FT4 < 5^th percentile with TSH between 2.5-97.5^th percentiles and a reference group with adequate FT4 levels, i.e., between 10 - 90^th percentiles and normal TSH levels.

Results: 68 women on T4 replacement therapy were excluded and 12 women had incomplete data. Data-analysis refers to 2762 women. Of these, 122 had hypothyroxinaemia and 2114 belonged to the reference group. There were 147 women with low ferritin (< 5^th percentile: < 17 µg/l), 129 women with high CRP (> 95^th percentile: > 14.58 mg/l) and 136 women with a high Il-6 level (> 95^th percentile: > 3.71 µg/l). Significantly more women with low ferritin, high CRP and high IL-6 status belonged to the hypothyroxinemic group compared to the control group (χ² (1): 12.9, 11.1 and 10.9, all P < 0.001). Moreover, hypothyroxinemic women had significantly lower hCG levels (MW-U: Z = 4.6, P < 0.001) than the control group. Multiple logistic regression showed that hypothyroxinemia was independently associated with low iron status (OR: 3.6, 95%CI: 2.1-6.4), high CRP (OR: 2.1, 95%CI: 1.1-4.2), high IL-6 (OR: 2.3, 95%CI: 1.2-4.5), lower log hCG levels (OR: 6.6, 95%CI: 2.6-16.6), and higher age (OR: 1.08, 095%CI: 1.03-1.14).

Conclusion: Different modulators of OS – which are all separately associated with poor obstetric outcome – seem to be associated with hypothyroxinaemia during early gestation calling into question whether hypothyroxinaemia should be thought of as an example of OS, as reported in non-thyroidal illness.