Uncontrolled Thyroid during Pregnancy Alters the Circulative and Exerted Metabolome.

Normal levels of thyroid hormones (THs) are essential for a normal pregnancy outcome, fetal growth and the normal function of the central nervous system. Hypothyroidism, a common endocrine disorder during pregnancy, is a significant metabolic factor leading to cognitive impairments. It is essential to investigate whether patients with thyroid dysfunction may present an altered circulative and excreted metabolic profile, even after receiving treatment with thyroxine supplements. NMR metabolomics was employed to analyze 90 serum and corresponding colostrum samples. Parallel analyses of the two biological specimens provided a snapshot of the maternal metabolism through the excretive and circulating characteristics of mothers. The metabolomics data were analyzed by performing multivariate statistical, biomarker and pathway analyses. Our results highlight the impact of hypothyroidism on metabolites' composition during pregnancy and lactation. Thyroid disorder causing metabolite fluctuations may lead to impaired lipid and glucose metabolic pathways as well as aberrant prenatal neurodevelopment, thus posing a background for the occurrence of metabolic syndrome or neurogenerative diseases later in life. This risk applies to not only untreated but also hypothyroid women under replacement therapy since our findings in both biofluids framed a different metabolic phenotype for the latter group, thus emphasizing the need to monitor women adequately after treatment initiation.

Early Human-Milk Metabolome in Cases of Intrauterine Growth-Restricted and Macrosomic Infants.

BACKGROUND: Abnormal fetal growth is associated with short-term and long-term metabolic dysregulation and susceptibility to obesity-related disorders. Maternal milk, the ideal source of infantile nutrition, protects from metabolic diseases in adulthood. By applying nuclear magnetic resonance (NMR) metabolomics, this study investigated the metabolic profile of early human milk/colostrum (EHM/C) at the extremes of fetal-growth conditions, which could affect its nutritional value. METHODS: From 98 mothers delivering 60 appropriate-for-gestational-age (AGA), 19 large-for-gestational-age (LGA), and 19 intrauterine growth-restricted (IUGR) full-term neonates, milk samples collected on the third to fourth day post partum were examined by NMR spectroscopy. Multivariate data analysis elicited information from NMR spectra and probed to metabolic signatures of EHM/C. RESULTS: LGA and IUGR EHM/C samples depicted increased content in lactose, citric acid, choline, phosphocholine, and N-acetylglutamine. AGA samples exhibited increased isoleucine and valine. Metabolic pathways involved were valine, leucine/isoleucine biosynthesis and degradation, glycerophospholipid metabolism, aminoacyl-transfer RNA biosynthesis, and citrate cycle. Orthogonal projections to latent structures discriminant analysis models were validated. CONCLUSION: This holistic metabolomics study framed an increased content of certain essential nutrients in EHM/C samples following the birth of LGA and IUGR infants prone to short- and long-term metabolic disorders, thus stressing additional benefits of early breastfeeding. Assessing the metabolic profile of EHΜ/C enables evaluation of its nutrition value, adjusted to fetal growth, and introduction of appropriate dietary interventions.

The effect of intrauterine growth on leukocyte telomere length at birth.

Objective: Telomeres are specialized nucleoprotein structures located at the ends of chromosomes, which play a crucial role in genomic stability. Telomere shortening has been proposed as a biomarker for the onset of age-related diseases. This study aimed to determine whether restricted or increased intrauterine growth affects leukocyte telomere length (LTL) at birth. Materials and methods: One hundred sixty-five (n = 165) full-term neonates participated in the study. Fetuses were classified as intrauterine growth restriction (IUGR, n = 21), large-for-gestational-age (LGA, n = 15), or appropriate-for-gestational-age (AGA, n = 129), based on customized birth-weight standards. Mixed arteriovenous cord blood samples were collected for isolation of leukocyte DNA. The LTL was measured using multiplex monochrome quantitative real-time PCR and telomeric restriction fragments through Southern blot analysis (terminal restriction fragment [TRF]). Results: Despite differences among groups in birth weight, length and head circumference, LTL did not differ among AGA (6.78 ± 0.58), IUGR (10.54 ± 1.80), and LGA (11.95 ± 2.42) neonates (p = .098). Cord blood IGF-1 and IGFBP-3 concentrations were higher in the LGA group. LTL positively correlated with birth length (r = 0.176, p = .032). Conclusions: Intrauterine growth does not seem to affect LTL at birth. Further studies, comprising a larger sample size of IUGR, LGA, and AGA neonates, are required to determine whether growth at birth influences LTL.

Heart rate as a therapeutic target in angina pectoris.

Heart rate is a major determinant of cardiac output and myocardial oxygen utilization and is increasingly being nominated as a modifiable risk factor for cardiovascular disease. Despite this evidence, screening strategies for preventing cardiovascular diseases do not include routine assessment of resting heart rate. Reasonably, heart rate reduction has been suggested as a useful approach against angina pectoris in subjects with acute or chronic coronary syndromes. Accordingly, reduction of heart rate in patients with stable angina could be an additional goal of therapy. Important data have shown retrospectively the beneficial effect of heart rate-lowering drugs, such as betaadrenoceptor antagonists, non-dihydropyridine calcium channel antagonists, as well as other agents, on several parameters in patients with coronary artery disease and stable angina. However, additional data are now being sought to assess the impact of this approach on clinical practice.

Insight to the pathophysiology of stable angina pectoris.

Atherosclerosis is a chronic disease which mainly represents an inflammatory response in the vessels. Myocardial ischemia manifested by angina pectoris can be either acute or chronic and usually is a result of imbalance between myocardial oxygen supply and myocardial oxygen demand. Chronic stable angina is chest discomfort attributed to myocardial ischemia without the presence of necrosis and is the most common symptom encountered by emergency room physicians. A growing amount of data has shown that endothelial dysfunction, is now considered an important early event in the development of atherosclerosis, while in the absence of angiographically obstructive coronary artery disease, anginal chest pain is often attributed to microvascular coronary dysfunction. Moreover, atheroma formation and in turn, atherosclerotic plaques seem to affect coronary flow, given that multivessel flow-limiting obstructions are observed in patients with chronic coronary syndrome. Morphological changes of diseased arteries related to significant atherosclerosis, such as vascular remodeling may also result in stable angina or claudication. However, several issues with respect to the comprehension of the pathophysiology of the chronic coronary syndrome have not been fully elucidated.

The role of microRNAs in the initiation and progression of stable atheromatous plaque.

Atherosclerosis is a chronic process related to several underlying mechanisms leading to the formation and evolution of atherosclerotic plaque. Of great interest are during the last years short, non-coding RNAs, called microRNAs and responsible for several aspects of homeostasis and disease. According to the available data microRNAs are expressed in the cardiovascular system and have key roles in normal states, as well as in disease development and progression. Moreover, it has been shown that they contribute to atherogenesis, coronary artery disease and myocardial infarction. Importantly, microRNAs circulate in the bloodstream, while they exist in tissues, affect plaque initiation and progression and seem to be essential biomarkers of atherosclerosis. Therefore, understanding the role of these molecules may be of great importance in the understanding of the pathogenesis of atheromatous plaque providing new evidence for diagnosis and treatment of atherosclerosis and its' clinical presentation.