Determination of steroid reference intervals in a pregnancy population

Abstract Steroids, including mineralocorticoids, glucocorticoids, and sex hormones play a critical role in pregnancy. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis offers an opportunity to conduct simultaneous multiplex steroid analysis within a given sample. This paper describes the LC-MS/MS steroid analysis method developed for assessing plasma specific reference ranges of 18 steroids from plasma samples (200 µL) of pregnant women participating in the PREDO study. Samples were prepared using supported liquid extraction and analyzed on an Acquity I-Class UPLC and a QTrap6500 + mass spectrometer. Mass spectrometry parameters were optimized for each steroid and chromatographic separation of 18 steroids was developed. Changes in steroid levels across pregnancy were assessed. Samples were collected after an overnight fast between 07:00 and 09:00. Data from 257 samples from 96 women with uncomplicated pregnancy (women with pre-pregnancy normal weight and no diabetes or hypertensive disorders before or during pregnancy, who delivered a live child at ≥ 37 weeks of gestation with appropriate for gestational age birth weight) were analyzed to calculate steroid reference ranges over three time points, between 11.6 and 14.3, 17.7–22.9, and 25.6–29.0 pregnancy weeks. Levels of progestogens, glucocorticoids, mineralocorticoids, estrogens, their precursors, and metabolites increased significantly across pregnancy. Androgen levels remained stable, except for a decrease in 5α-dihydrotestosterone. The LC-MS/MS method also showed validity in analyses of 917 samples of 328 women with complicated pregnancies. The method is suitable for the analysis of 18 steroids in plasma during pregnancy and the investigation of pregnancy complications, fetal growth, and development after birth.Abstract Steroids, including mineralocorticoids, glucocorticoids, and sex hormones play a critical role in pregnancy. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis offers an opportunity to conduct simultaneous multiplex steroid analysis within a given sample. This paper describes the LC-MS/MS steroid analysis method developed for assessing plasma specific reference ranges of 18 steroids from plasma samples (200 µL) of pregnant women participating in the PREDO study. Samples were prepared using supported liquid extraction and analyzed on an Acquity I-Class UPLC and a QTrap6500 + mass spectrometer. Mass spectrometry parameters were optimized for each steroid and chromatographic separation of 18 steroids was developed. Changes in steroid levels across pregnancy were assessed. Samples were collected after an overnight fast between 07:00 and 09:00. Data from 257 samples from 96 women with uncomplicated pregnancy (women with pre-pregnancy normal weight and no diabetes or hypertensive disorders before or during pregnancy, who delivered a live child at ≥ 37 weeks of gestation with appropriate for gestational age birth weight) were analyzed to calculate steroid reference ranges over three time points, between 11.6 and 14.3, 17.7–22.9, and 25.6–29.0 pregnancy weeks. Levels of progestogens, glucocorticoids, mineralocorticoids, estrogens, their precursors, and metabolites increased significantly across pregnancy. Androgen levels remained stable, except for a decrease in 5α-dihydrotestosterone. The LC-MS/MS method also showed validity in analyses of 917 samples of 328 women with complicated pregnancies. The method is suitable for the analysis of 18 steroids in plasma during pregnancy and the investigation of pregnancy complications, fetal growth, and development after birth

A polyepigenetic glucocorticoid exposure score at birth and childhood mental and behavioral disorders

BackgroundMaternal depression and anxiety during pregnancy may enhance fetal exposure to glucocorticoids (GCs) and harm neurodevelopment. We tested whether a novel cross-tissue polyepigenetic biomarker indicative of in utero exposure to GC is associated with mental and behavioral disorders and their severity in children, possibly mediating the associations between maternal prenatal depressive and anxiety symptoms and these child outcomes.MethodsChildren (n = 814) from the Prediction and Prevention of Preeclampsia and Intrauterine Growth Restriction (PREDO) study were followed-up from birth to age 7.1–10.7 years. A weighted polyepigenetic GC exposure score was calculated based on the methylation profile of 24 CpGs from umbilical cord blood. Child diagnosis of mental and behavioral disorder (n = 99) and its severity, defined as the number of days the child had received treatment (all 99 had received outpatient treatment and 8 had been additionally in inpatient treatment) for mental or behavioral disorder as the primary diagnosis, came from the Care Register for Health Care. Mothers (n = 408) reported on child total behavior problems at child's age of 2.3–5.8 years and their own depressive and anxiety symptoms during pregnancy (n = 583).ResultsThe fetal polyepigenetic GC exposure score at birth was not associated with child hazard of mental and behavioral disorder (HR = 0.82, 95% CI 0.54; 1.24, p = 0.35) or total behavior problems (unstandardized beta = −0.10, 95% CI -0.31; 0.10, p = 0.33). However, for one standard deviation decrease in the polyepigenetic score, the child had spent 2.94 (95%CI 1.59; 5.45, p ConclusionsThese findings suggest that fetal polyepigenetic GC exposure score at birth was not associated with any mental or behavioral disorder diagnosis or mother-rated total behavior problems, but it may contribute to identifying children at birth who are at risk for more severe mental or behavioral disorders.</p

Maternal influences on fetal brain development: the role of nutrition, infection and stress, and the potential for intergenerational consequences.

An optimal early life environment is crucial for ensuring ideal neurodevelopmental outcomes. Brain development consists of a finely tuned series of spatially and temporally constrained events, which may be affected by exposure to a sub-optimal intra-uterine environment. Evidence suggests brain development may be particularly vulnerable to factors such as maternal nutrition, infection and stress during pregnancy. In this review, we discuss how maternal factors such as these can affect brain development and outcome in offspring, and we also identify evidence which suggests that the outcome can, in many cases, be stratified by socio-economic status (SES), with individuals in lower brackets typically having a worse outcome. We consider the relevant epidemiological evidence and draw parallels to mechanisms suggested by preclinical work where appropriate. We also discuss possible transgenerational effects of these maternal factors and the potential mechanisms involved. We conclude that modifiable factors such as maternal nutrition, infection and stress are important contributors to atypical brain development and that SES also likely has a key role

Fetal programming of neuropsychiatric disorders by maternal pregnancy depression: a systematic mini review

BACKGROUND: Maternal depression complicates a large proportion of pregnancies. Current evidence shows numerous harmful effects on the offspring. Reviews, which include depression, concluded that stress has harmful effects on the offspring's outcomes neuro-cognitive development, temperament traits, and mental disorders. OBJECTIVE: This mini review of recent studies, sought to narrow the scope of exposure and identify studies specifically assessing prenatal depression and offspring neuropsychiatric outcomes. STUDY ELIGIBILITY CRITERIA: The review included longitudinal, cohort, cross-sectional, clinical, quasi-experimental, epidemiological, or intervention study designs published in English from 2014 to 2018. PARTICIPANTS: Study populations included mother-child dyads, mother-father-child triads, mother-alternative caregiver-child triads, and family studies utilizing sibling comparisons. METHODS: We searched PubMED and Web of Science. Study inclusion and data extraction were based on standardized templates. The quality of evidence was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Thirteen studies examining neuropsychiatric outcomes were included. We judged the evidence to be moderate to high quality. CONCLUSIONS: Our review supports that maternal prenatal depression is associated with neuropsychiatric adversities in children.Peer reviewe

Application of multi-layer structures of wafer-type made of composite materials for creating microwave antenna radomes

A new type of microwave antenna radome structure for aircrafts is suggested, which is a waffle radomes that possess improved characteristics if compared to traditional structures. Design peculiarities of such radome walls, waffle structures and their load-bearing elements made of dielectric composite materials are considered. A calculation model for such structures is justified and a methodology of selecting reasonable layer parameters according to radome’s level of radiolucency. A comparison of radio engineering characteristics of waffle and traditional three-layer structures of radome’s walls in a wide range of electromagnetic waves’ incidence angles in presence of mass limitations is conducted

HUMAN DIMENSION OF START-UP

Abstract. Start-up is a young and very small enterprise which staffing and human relationships are different from the internal environment of larger enterprises. Research has therefore focused on founders/leaders of start-ups and relationships inside start-up teams. The result of the research is the basic personal characteristics of the leading people (age, education, reasons for entering the business and others), the quality of their leadership and the quality of teamwork. Since a start-up is developing vigorously, leadership and teamsmanship are monitored on the base of business idea development and investment cycle. Start-up founders are better leaders than managers, teams are better at handling extraordinary situations than standard operation, quality of leadership is situationally conditioned to a certain extent by start-up development phase. Start-ups contain contradictions with significant asymmetry, which are the expression of their limited strengths and considerable weaknesses. The lack of living and work experiences is substituted by the enthusiasm, the diligence and the sense of teamwork that have their limits, and therefore the solution is to professionalize the start-up in in the later stages of its development. Keywords: start-up, founder, leadership, team, Slovakia. JEL Classification M10, G24 Formulas: 0; fig.: 0; tabl.: 5; bibl.: 31.</jats:p

Human dimension of start-up

Start-up is a young and very small enterprise which staffing and human relationships are different from the internal environment of larger enterprises. Research has therefore focused on founders/leaders of start-ups and relationships inside start-up teams. The result of the research is the basic personal characteristics of the leading people (age, education, reasons for entering the business and others), the quality of their leadership and the quality of teamwork. Since a start-up is developing vigorously, leadership and teamsmanship are monitored on the base of business idea development and investment cycle. Start-up founders are better leaders than managers, teams are better at handling extraordinary situations than standard operation, quality of leadership is situationally conditioned to a certain extent by start-up development phase. Start-ups contain contradictions with significant asymmetry, which are the expression of their limited strengths and considerable weaknesses. The lack of living and work experiences is substituted by the enthusiasm, the diligence and the sense of teamwork that have their limits, and therefore the solution is to professionalize the start-up in in the later stages of its development