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The multiple aspects of thyroid (dys)function in pregnant women

par Sitoris, Georgiana
Président du jury Verhoeven, Caroline
Promoteur Poppe, Kris
Co-Promoteur Rozenberg, Serge
Publication Non publié, 2024-08-28

Thèse de doctorat

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Résumé :

Thyroid function in pregnant women is governed by numerous factors. Among these, thyroid autoimmunity (TAI) plays a crucial role, as both thyroid dysfunction and TAI are linked to an increased risk of miscarriage, preeclampsia, and preterm delivery. Other maternal factors can also influence thyroid function, such as body mass index (BMI), iron and iodine levels, and ethnic origin. We have investigated the impact of these variables on thyroid function, and our findings have been published and included in a previous thesis. Many questions remain unanswered, such as the lack of consensus regarding the necessity of universal screening for thyroid disorders. The current approach is to perform targeted screening only for women at risk of developing hypothyroidism (clinical/subclinical) during pregnancy, rather than universal screening.Several reasons explain why universal screening has not yet been implemented: firstly, pregnancy outcomes are not always adjusted for certain confounding factors such as other maternal pathologies (e.g., gestational diabetes (GDM) and hypertension) or factors of placental origin (which may differ according to the sex of the foetus). These factors can alter the association between thyroid disorders and pregnancy outcomes. Secondly, certain outcomes related to thyroid dysfunction have not been investigated in the same way as miscarriage and preterm delivery. Finally, there are few studies evaluating the impact of thyroid hormone treatment (LT4) in women with subclinical hypothyroidism (SCH).The work compiled in this thesis aims to improve our knowledge in this field.First study: We evaluated the association between thyroid dysfunction and TAI and maternal and neonatal outcomes after excluding women treated with thyroid hormones or those who had received antithyroid medication from the study. These analyses were adjusted for several common confounding factors such as smoking, age, and BMI, as well as other gestational pathologies such as hypertension and gestational diabetes. The results of this study reported that women with TAI had a higher risk of neonatal intensive care admission and that women with SCH showed a tendency towards an increased risk of preeclampsia and low birth weight.We also recently analyzed thyroid pathology in relation to fetal sex, as the concentrations of placental substances, such as chorionic gonadotropin hormone (hCG) and vascular endothelial growth factor (VEGF), might have a different impact on thyroid function depending on gender. In daily practice, placental substances are not measured. Some studies report a different placental weight depending on fetal sex. Consequently, we conducted a second study to evaluate maternal thyroid function according to fetal sex. The results showed that women pregnant with a male fetus had a slight increase in TSH levels and a higher upper limit of the TSH reference value in the first trimester compared to pregnancies with a female fetus. We hypothesized that this difference might be related to higher hCG levels in women pregnant with a female fetus, but we were unable to analyze hCG levels in this retrospective study as these data were not available.In the third study, we investigated the association between TAI and GDM, a pregnancy complication with significant morbidity for both mother and child. The underlying hypothesis is that TAI is the main cause of SCH and is also a condition associated with an inflammatory state like GDM. Other studies report an association between SCH and a high prevalence of GDM, but when our study began, these data were contested. In our study, we included only women who had an oral glucose tolerance test (OGTT). GDM was defined according to the criteria accepted by the WHO. The results showed that among older euthyroid women, TAI was independently associated with GDM. Additionally, consistent with the literature, older age and higher BMI were strongly associated with the prevalence of GDM.Finally, another argument for introducing universal screening for thyroid dysfunction in pregnant women is to demonstrate that a well-established and safe medication exists and reduces maternal and/or fetal complications. In the case of thyroid dysfunction and pregnancy, this medication is LT4.Particularly in the case of women with SCH and without TAI, there is only one study providing evidence of the beneficial impact of LT4. Moreover, this study only analyzed preterm birth rates.Consequently, in the fourth study of this thesis, we evaluated the effectiveness of LT4 treatment in reducing maternal complications. We reported that women with SCH had a higher prevalence of preeclampsia and GDM compared to euthyroid women, whereas this was not the case in women treated with LT4, even when LT4 treatment was initiated after the first trimester. Additionally, the prevalence of iron deficiency anemia decreased in women treated with LT4.In this thesis, we discuss these four studies in detail, placing them in a broader perspective on thyroid disorders during pregnancy. We also propose future research directions.