RESUMO
Previous studies show differentially expressed long non-coding RNA present in the placenta from women with pre-eclampsia, potentially playing a vital role in the pathogenesis of the complication. In a published microarray study, Ribonuclease P RNA component H1 was decreased in leukocytes from women that later developed pre-eclampsia. We hypothesized that Ribonuclease P RNA component H1 decreased during pregnancy in women developing pre-eclampsia and important for the development of the complication. We isolated RNA from extracellular vesicles, leukocytes and plasma using blood samples taken at weeks 22-24 and 36-38 in women who subsequently developed pre-eclampsia and from healthy pregnancy. The expression of Ribonuclease P RNA component H1 was quantified using qPCR. Expression of Ribonuclease P RNA component H1 at 22-24 weeks was further examined to investigate its discriminatory potential of subsequent pre-eclampsia and association with clinical markers. We found lower expression of Ribonuclease P RNA component H1 in leukocytes at 22-24 and 36-38 weeks amongst women who subsequent developed pre-eclampsia compared with those who did not, while increased Ribonuclease P RNA component H1 expression was found in plasma at 36-38 weeks. Pre-eclampsia risk factors could not account for this difference in the Ribonuclease P RNA component H1 expression. Prediction of pre-eclampsia at 22-24 weeks using Ribonuclease P RNA component H1 expression in leukocytes in addition to the screening algorithm used today had a significantly better performance. In conclusion, Ribonuclease P RNA component H1 expression in leukocytes was significantly decreased in women with pre-eclampsia, and the expression at 22-24 weeks associated with the subsequent development of pre-eclampsia. Ribonuclease P RNA component H1 in leukocytes may be a useful biomarker for prediction and/or early detection of pre-eclampsia and an unknown regulator of the signaling affecting immune cells.
Assuntos
Leucócitos , Pré-Eclâmpsia , RNA Longo não Codificante , Humanos , Feminino , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/diagnóstico , Gravidez , Leucócitos/metabolismo , RNA Longo não Codificante/sangue , RNA Longo não Codificante/genética , Adulto , Biomarcadores/sangueRESUMO
Glucose is a major energy substrate for the fetus, including liver, heart, and brain metabolism. The umbilical vein (UV) blood flow supplies the fetal liver directly from the placenta, whereas a fraction is shunted via ductus venosus (DV) to the fetal systemic circulation bypassing the fetal liver. We hypothesized UV glucose concentration to be a major regulator of the distribution of glucose supply between the fetal liver and DV, and explored the influence of maternal metabolic status on this distribution. We included 124 healthy women with normal singleton pregnancies, scheduled for elective cesarean section. UV and DV blood flow measurements were performed by Doppler ultrasound immediately before, and blood samples were obtained during surgery. UV blood flow was significantly correlated with DV blood flow, liver blood flow, and the DV shunting fraction, while UV glucose concentration was not. For normal-weight mothers, the maternal-fetal glucose gradient was positively correlated with DV shunting fraction, and negatively with liver blood flow. For the fetuses of the overweight mothers no such correlation was found. This indicates that within the normal physiological range the human fetus makes adaptations of blood flow to ensure individual needs related to the offered maternal energy supply.
Assuntos
Glucose/análise , Hemodinâmica , Fígado , Fluxo Sanguíneo Regional , Veias Umbilicais/irrigação sanguínea , Adulto , Cesárea , Estudos de Coortes , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Fígado/irrigação sanguínea , Fígado/embriologia , Saúde Materna , Estado Nutricional , GravidezRESUMO
BACKGROUND: Reduced lung function at birth has evident antenatal origins and is associated with an increased risk of wheezing and asthma later in life. Little is known about whether blood flow in the fetal pulmonary artery, may impact postnatal lung function. OBJECTIVE: Our primary aim was to investigate the potential associations between fetal Doppler blood flow velocity measures in the fetal branch pulmonary artery, and infant lung function by tidal flow-volume (TFV) loops at three months of age in a low-risk population. Our secondary aim was to explore the association between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries, and the same lung function measures. METHODS: In 256 non-selected pregnancies from the birth cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) we performed fetal ultrasound examination with Doppler blood flow velocity measurements at 30 gestational weeks (GW). We recorded the pulsatility index, peak systolic velocity, time-averaged maximum velocity, acceleration time/ejection time ratio, and time velocity integral primarily in the proximal pulmonary artery close to the pulmonary bifurcation. The pulsatility index was measured in the umbilical and middle cerebral arteries and the peak systolic velocity in the middle cerebral artery. The cerebro-placental ratio (ratio between pulsatility index in the middle cerebral and umbilical arteries) was calculated. Infant lung function was assessed using TFV loops in awake, calmly breathing three months old infants. The outcome was the time to peak tidal expiratory flow to expiratory time ratio (tPTEF/tE), tPTEF/tE <25th percentile, and tidal volume per kg body weight (VT/kg). Potential associations between fetal Doppler blood flow velocity measures and infant lung function were assessed using linear and logistic regressions. RESULTS: The infants were born at median (min - max) 40.3 (35.6 - 42.4) GW, with a mean (SD) birth weight of 3.52 (0.46) kg, and 49.4% were females. The mean (SD) tPTEF/tE was 0.39 (0.1) and the 25th percentile was 0.33. Neither univariable nor multivariable regression models revealed any associations between fetal pulmonary blood flow velocity measures and tPTEF/tE, tPTEF/tE <25th percentile, or VT/kg at three months of age. Similarly, we did not observe associations between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries and infant lung function measures. CONCLUSION: In a cohort of 256 infants from the general population, fetal third-trimester Doppler blood flow velocity measures in the branch pulmonary, umbilical, and middle cerebral arteries were not associated with infant lung function measures at three months of age.
Assuntos
Placenta , Artéria Pulmonar , Recém-Nascido , Criança , Lactente , Humanos , Gravidez , Feminino , Masculino , Artéria Pulmonar/diagnóstico por imagem , Estudos de Coortes , Velocidade do Fluxo Sanguíneo/fisiologia , Estudos Prospectivos , Pulmão/diagnóstico por imagem , Ultrassonografia Doppler , Artérias Umbilicais/fisiologia , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Women with a history of gestational diabetes mellitus and preeclampsia are at increased risk of cardiovascular disease later in life, but the mechanism remains unclear. The aim of the study was to evaluate the association between CXC chemokine ligand 16 and indices of glucose metabolism, dyslipidemia and systemic inflammation in gestational diabetes mellitus and preeclampsia. METHODS: This sub-study of the population-based prospective cohort included 310 women. Oral glucose tolerance test was performed during pregnancy and 5 years later along with lipid analysis. CXC chemokine ligand 16 was measured in plasma (protein) and peripheral blood mononuclear cells (messenger RNA) during pregnancy and at follow-up. RESULTS: Circulating CXC chemokine ligand 16 was higher in gestational diabetes mellitus women early in pregnancy and at follow-up, while higher in preeclampsia women late in pregnancy compared to control women. Messenger RNA of CXC chemokine ligand 16 in peripheral blood mononuclear cells were lower in gestational diabetes mellitus and preeclampsia women compared to control women. Increased circulating CXC chemokine ligand 16 level was associated with a higher apolipoprotein B and low-density lipoprotein cholesterol in gestational diabetes mellitus women but not in normal pregnancy at follow-up. CONCLUSION: Our study shows that women with gestational diabetes mellitus and preeclampsia had a dysregulated CXC chemokine ligand 16 during pregnancy, and in gestational diabetes mellitus, the increase in CXC chemokine ligand 16 early in pregnancy and after 5 years was strongly associated with their lipid profile.
Assuntos
Quimiocina CXCL16/sangue , Diabetes Gestacional/sangue , Lipoproteínas/sangue , Pré-Eclâmpsia/sangue , Adulto , Apolipoproteína B-100/sangue , Biomarcadores/sangue , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Quimiocina CXCL16/genética , LDL-Colesterol/sangue , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/genética , Feminino , Seguimentos , Humanos , Mediadores da Inflamação/sangue , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/genética , Gravidez , Estudos Prospectivos , Fatores de Tempo , Regulação para CimaRESUMO
BACKGROUND: Neonatal body composition has implications for the health of the newborn both in short and long term perspective. The objective of the current study was first to explore the association between maternal BMI and metabolic parameters associated with BMI and neonatal percentage body fat and to determine to which extent any associations were modified if adjusting for placental weight. Secondly, we examined the relations between maternal metabolic parameters associated with BMI and placental weight. METHODS: The present work was performed in a subcohort (nâ=â207) of the STORK study, an observational, prospective study on the determinants of fetal growth and birthweight in healthy pregnancies at Oslo University Hospital, Norway. Fasting glucose, insulin, triglycerides, free fatty acids, HDL- and total cholesterol were measured at week 30-32. Newborn body composition was determined by Dual-Energy X-Ray Absorptiometry (DXA). Placenta was weighed at birth. Linear regression models were used with newborn fat percentage and placental weight as main outcomes. RESULTS: Maternal BMI, fasting glucose and gestational age were independently associated with neonatal fat percentage. However, if placental weight was introduced as a covariate, only placental weight and gestational age remained significant. In the univariate model, the determinants of placenta weight included BMI, insulin, triglycerides, total- and HDL-cholesterol (negatively), gestational weight gain and parity. In the multivariable model, BMI, total cholesterol HDL-cholesterol, gestational weight gain and parity remained independent covariates. CONCLUSION: Maternal BMI and fasting glucose were independently associated with newborn percentage fat. This effect disappeared by introducing placental weight as a covariate. Several metabolic factors associated with maternal BMI were associated with placental weight, but not with neonatal body fat. Our findings are consistent with a concept that the effects of maternal BMI and a number of BMI-related metabolic factors on fetal fat accretion to a significant extent act by modifying placental weight.