Steroid profiling in pregnancy: a focus on the human fetus.

In this review we focused on steroid metabolomics in human fetuses and newborns and its role in the physiology and pathophysiology of human pregnancy and subsequent stages of human life, and on the physiological relevance of steroids influencing the nervous systems with regards to their concentrations in the fetus. Steroid profiling provides valuable data for the diagnostics of diseases related to altered steroidogenesis in the fetal and maternal compartments and placenta. We outlined a potential use of steroid metabolomics for the prediction of reproductive disorders, misbalance of hypothalamic-pituitary-adrenal axis, and impaired insulin sensitivity in subsequent stages of human life. A possible role of steroids exhibiting a non-genomic effect in the development of gestational diabetes and in the neuroprotection via negative modulation of AMPA/kainate receptors was also indicated. Increasing progesterone synthesis and catabolism, declining production of tocolytic 5ß-pregnane steroids, and rising activities of steroid sulfotransferases with the approaching term may be of importance in sustaining pregnancy. An increasing trend was demonstrated with advancing gestation toward the production of ketones (and 3ß-hydroxyl groups in the case of 3α-hydroxy-steroids) was demonstrated in the fetus on the expense of 3α-hydroxy-, 17ß-hydroxy-, and 20α-hydroxy-groups weakening in the sequence C17, C3, and C20. There was higher production of active progestogen but lower production of active estrogen and GABAergic steroids with the approaching term. Rising activities of placental CYP19A1 and oxidative isoforms of HSD17B, and of fetal CYP3A7 with advancing gestation may protect the fetus from hyperestrogenization. This article is part of a Special Issue entitled 'Pregnancy and Steroids'.

What is the benefit of screening for thyroid function in pregnant women in the detection of newly diagnosed thyropathies?

BACKGROUND: Thyroid gland disturbances are the most common endocrine disorders in pregnancy. There are some particular recommendations for the investigation of women in risk groups, but no consensus guidelines for general screening exists at present in the Czech Republic. AIM: The aim of our study was to determine whether universally conducted screening of pregnant women would reveal a significant number thyropathies. MATERIAL AND METHODS: We examined 592 pregnant women for thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels and for autoantibodies against thyroperoxidase (antiTPO) in the 6th - 10th week of their pregnancy. RESULTS: Levels of TSH, fT4 or antiTPO beyond laboratory reference limits were found by gynaecologists in 214 women (36.1%) and 141 of whom (23.8%) underwent endocrinological examination. In the women without known risk factors (n=91) we found undiagnosed autoimmune thyroiditis in 20 cases (22 %) and in 7 cases (7.7%) some degree of subclinical hypothyroidism was confirmed. Finally, 18 (19.8%) women had hypothyroxinemia in the 1st trimester (fT4 average 8.76 pmol/L) with normal TSH levels. Altogether, a total of 45 women were succesfully identified (49.5% of the endocrinologically examined group without risk factors, i.e. 7.6% of the whole screened group) who warranted monitoring. Of 73 women (12.3%) who underwent screening and, despite recommendation, did not undergo endocrinological examination, there were 55 cases (9.3% of the screened group) with positive levels of antiTPO and with elevation of TSH above the upper normal limit. CONCLUSIONS: Of 592 women in the 6th - 10th week of pregnancy who underwent thyropathy screening, we newly diagnosed 3.4% of women with autoimmune thyroiditis, 1.2% with subclinical hypothyroidism and 3% with hypotyroxinemia, for whom n o thyropathy risk factor had been evident. Thyropathies were identified in 7.6% of probands. We believe that our results support the importance of universal screening in pregnancy.