The fetal liver exhibits marked sex differences at the protein level, and these are disturbed by maternal smoking. The foundations for smoke-induced post-natal diseases are likely to be due to sex-specific effects on diverse pathways.

BackgroundMaternal lifestyle factors, including smoking and increased body weight, increase risks of adult diseases such as metabolic syndrome and infertility. The fetal thyroid gland is essential for the control of fetal metabolic rate, cardiac output, and brain development. Altered fetal thyroid function may contribute to increased disease onset later in life. Here, we investigated the impact of maternal smoking and high maternal weight on human fetal thyroid function during the second trimester.MethodsThyroid glands and plasma were collected from fetuses electively terminated in the second trimester (normally progressing pregnancies). Plasma total triiodothyronine (T3) and total thyroxine (T4) were measured by solid-phase extraction-liquid chromatography-tandem mass spectrometry. Fetal plasma thyroid-stimulating hormone (TSH) levels were measured using a multiplex assay for human pituitary hormones. Histology and immunolocalization of thyroid developmental markers were examined in thyroid sections. Transcript levels of developmental, functional, apoptotic, and detoxification markers were measured by real-time PCR. Statistical analyses were performed using multivariate linear regression models with fetal age, sex, and maternal smoking or maternal body mass index (BMI) as covariates.ResultsMaternal smoking was associated with significant changes in fetal plasma T4 and TSH levels during the second trimester. Smoke-exposed thyroids had reduced thyroid GATA6 and NKX2-1 transcript levels and altered developmental trajectories for ESR2 and AHR transcript levels. Maternal BMI > 25 was associated with increased fetal thyroid weight, increased plasma TSH levels, and abnormal thyroid histology in female fetuses. Normal developmental changes in AHR and ESR1 transcript expression were also abolished in fetal thyroids from mothers with BMI > 25.ConclusionsFor the first time, we show that maternal smoking and high maternal BMI are associated with disturbed fetal thyroid gland development and endocrine function in a sex-specific manner during the second trimester. These findings suggest that predisposition to post-natal disease is mediated, in part, by altered fetal thyroid gland development.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1183-7) contains supplementary material, which is available to authorized users.

A best evidence topic in interventional cardiac surgery was written according to a structured protocol. The question we addressed related to the elevation of markers of cardiac damage associated with percutaneous coronary intervention (PCI). We explored and compared the clinical and prognostic relevance of the elevation of creatinine kinase-myocardial band (CK-MB) and cardiac troponin (cTn) levels during the periprocedural period and the post-procedural period, respectively, following an emergency or elective PCI. We found in excess of 390 papers after a systematic literature search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. From the best evidence available it appears that the monitoring of cardiac biomarkers following a PCI can provide important clinical information about the health of the myocardium, as well as prognostic information on short to mid-term outcomes of mortality up to 3 years. The narrow evidence base advocates the use of periprocedural CK-MB monitoring, recommending that an elevation in CK-MB is a significant predictor of adverse events. Troponins remain a precise and reliable marker of cardiac damage; however, current evidence argues that cTn holds little prognostic relevance until the degree of elevation is almost five times the upper limit of normal (ULN). Thus, the best evidence recommends the use of periprocedural CK-MB routinely during PCI to provide clinical and prognostic information about the degree of myocardial injury and risk of post-procedural morbidity and mortality.

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