TY - JOUR A1 - Lu, Yong-Ping A1 - Hasan, Ahmed A. A1 - Zeng, Shufei A1 - Hocher, Berthold T1 - Plasma ET-1 concentrations are elevated in pregnant women with hypertension - meta-analysis of clinical studies JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie ; official organ of the Deutsche Liga zur Bekämpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft N2 - Background/Aims: The ET system might be involved in the pathogenesis of hypertensive disorders during pregnancy. The objective is to analyse the impact of ET-1 in hypertensive pregnant women by a strict meta-analysis of published human clinical studies. Methods: Based on the principle of Cochrane systematic reviews, Cohort studies in PubMed (Medline), Google Scholar and China Biological Medicine Database (CBM-disc) designed to identify the role of endothelin-1 (ET-1) in the pathophysiology of gestational hypertension and preeclampsia were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects model. Results: Sixteen published cohort studies including 1739 hypertensive cases and 409 controls were used in the meta-analysis. ET-1 plasma concentrations were higher in hypertensive pregnant women as compared to the controls (mean difference between groups: 19.02 [15.60～22.44], P < 0.00001,). These finding were driven by severity of hypertension and/or degree of proteinuria. Conclusion: Plasma ET-1 concentrations are elevated in hypertensive disorders during human pregnancy. In particular women with preeclampsia (hypertensive pregnant women with proteinuria) have substantially elevated plasma ET-1 concentration as compared to pregnant women with normal blood pressure. KW - Et-1 KW - Pregnancy KW - Hypertension KW - Meta-analysis Y1 - 2017 U6 - https://doi.org/10.1159/000482004 SN - 1420-4096 SN - 1423-0143 VL - 42 IS - 4 SP - 654 EP - 663 PB - Karger CY - Basel ER - TY - JOUR A1 - He, Jing A1 - Liu, Zhi-Wei A1 - Lu, Yong-Ping A1 - Li, Tao-Yuan A1 - Liang, Xu-Jing A1 - Arck, Petra A1 - Huang, Si-Min A1 - Hocher, Berthold A1 - Chen, You-Peng T1 - A systematic review and meta-analysis of influenza a virus infection during pregnancy associated with an increased risk for stillbirth and low birth weight JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie ; official organ of the Deutsche Liga zur Bekämpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft N2 - Background/Aims: Impaired pregnancy outcomes, such as low birth weight are associated with increased disease risk in later life, however little is known about the impact of common infectious diseases during pregnancy on birth weight. The study had two aims: a) to investigate risk factors of influenza virus infection during pregnancy, and b) to analyze the impact of influenza virus infection on pregnancy outcome, especially birth weight. Methods: Prospective and retrospective observational studies found in PubMed, MEDLINE, Embase, Google Scholar, and WangFang database were included in this meta analysis. Data of included studies was extracted and analyzed by the RevMan software. Results: Pregnant women with anemia (P=0.004, RR=1.46, 95% CI: 1.13-1.88), obesity (P<0.00001, RR=1.35, 95% CI: 1.25-1.46) and asthma (P<0.00001, RR=1.99, 95% CI: 1.67-2.37) had higher rates of influenza virus infection. Regarding birth outcomes, influenza A virus infection did not affect the likelihood for cesarean section. Mothers with influenza had a higher rate of stillbirth (P=0.04, RR=2.36, 95% CI: 1.05-5.31), and their offspring had low 5-minute APGR Scores (P=0.009, RR=1.39, 95% CI: 1.08-1.79). Furthermore, the rate for birth weight < 2500g (P=0.04, RR=1.71, 95% CI: 1.03-2.84) was increased. Conclusion: Results of this study showed that anemia, asthma and obesity during pregnancy are risk factors influenza A virus infection during pregnancy. Moreover, gestational influenza A infection impairs pregnancy outcomes and increases the risk for low birth weight, a known risk factor for later life disease susceptibility. KW - Apgar score KW - Influenza virus KW - Offspring KW - Outcome KW - Pregnancy KW - Stillbirth KW - Birth weight Y1 - 2017 U6 - https://doi.org/10.1159/000477221 SN - 1420-4096 SN - 1423-0143 VL - 42 IS - 2 SP - 232 EP - 243 PB - Karger CY - Basel ER - TY - JOUR A1 - Fruscalzo, Arrigo A1 - Frommer, Julia-Marie A1 - Londero, Ambrogio P. A1 - Henze, Andrea A1 - Schweigert, Florian J. A1 - Nofer, Jerzy-Roch A1 - Steinhard, Johannes A1 - Klockenbusch, Walter A1 - Schmitz, Ralf A1 - Raila, Jens T1 - First trimester TTR-RBP4-ROH complex and angiogenic factors in the prediction of small for gestational age infant’s outcome JF - Archives of gynecology and obstetrics N2 - To study the role of the TTR-RBP4-ROH complex components (transthyretin, serum retinol binding protein, retinol) and of angiogenic factors PlGF (placental growth factor) and sFlt-1 (soluble fms-like tyrosine kinase-1) in pregnancies complicated by small for gestational age infants (SGA). Case control study conducted on maternal serum collected between 11 + 0 to 13 + 6 weeks of gestation. TTR, RBP4, ROH, PlGF and sFlt-1 were measured in SGA patients (birth weight < 10%) who delivered at term (n = 37) and before 37 weeks of gestation (n = 17) and in a matched control group with uneventful pregnancies (n = 37). We found decreased RBP4 in SGA patients that delivered fetuses < 3% and in fetuses delivered after the 37 weeks of gestation compared to controls [1.50 (95% CI 1.40-1.75) vs 1.62 (95% CI 1.47-1.98), p < 0.05]. Further, we found lower PlGF and sFlt-1 concentrations in SGA that delivered before 37 weeks of gestation compared to controls (respectively, PIGF and sFlt-1: 39.7 pg/ml (95% CI 32.3-66.3) vs 62.9 pg/ml (95% CI 45.2-78.4) and 906 pg/ml (95% CI 727-1626) vs 1610 pg/ml (95% CI 1088-212), p < 0.05). First trimester maternal serum RBP4 and angiogenic factors PlGF and sFlt-1 can differently predict the timing of delivery of pregnancies complicated by SGA fetuses. KW - Low birth weight KW - Small for gestational age KW - Pregnancy KW - First trimester KW - Marker KW - RBP4 KW - TTR KW - Retinol KW - Vitamin A KW - sFlt-1 KW - PlGF Y1 - 2017 U6 - https://doi.org/10.1007/s00404-017-4338-4 SN - 0932-0067 SN - 1432-0711 VL - 295 SP - 1157 EP - 1165 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Tsuprykov, Oleg A1 - Buse, Claudia A1 - Skoblo, Roman A1 - Haq, Afrozul A1 - Hocher, Berthold T1 - Reference intervals for measured and calculated free 25-hydroxyvitamin D in normal pregnancy JF - The Journal of Steroid Biochemistry and Molecular Biology N2 - The determination of free 25-hydroxyvitamin D (25(OH)D) as compared to the analysis of total 25-hydroxyvitamin D might reflect better the vitamin D status during pregnancy, since vitamin D-binding protein (DBP) concentrations increase throughout pregnancy and the vast majority of 25(OH)D is tightly bound to DBP thus strongly influencing total 25(OH)D. The concentration of the biologically active free 25(OH)D - on the other hand - is much less dependent on the DBP concentrations. The study was conducted in May-June 2016 in 368 Caucasian pregnant healthy women - residents of Northeastern Germany. Free 25(OH)D was either measured directly by commercial ELISA kit or assessed by calculation via total 25(OH)D, DBP, and albumin serum concentrations. Regardless of the detection method, free 25(OH)D lowers in the 3rd trimester comparing to the 1st trimester (by 12% and 21%, p < 0.05 and p < 0.001, for measured and calculated free 25(OH)D, respectively), whereas total 25(OH)D was not decreased in late pregnancy. DBP rises with gestational age. Total 25(OH)D was not correlated with serum calcium (p = 0.251), whereas free 25(OH)D was significantly (p = 0.007 for measured free 25(OH)D and p < 0.001 for calculated free 25(OH)D) positively correlated with calcium. All 25(OH) D isoforms were significantly negatively correlated with bone-specific alkaline phosphatase (BSAP), however the correlation strength was the lowest with total 25(OH)D (rho = -0.108, p = 0.038), whereas both measured and calculated free 25(OH)D revealed better associations with BSAP (rho = -0.203 and rho = -0.211 for measured and calculated free 25(OH)D, respectively, p < 0.001 for both). We established pregnancy trimester specific reference intervals for free measured and calculated 25(OH)D and DBP. Both measured and calculated free 25(OH)D showed better correlations with parameters of the endocrine vitamin D system (calcium and BSAP). Both ways of measuring free 25(OH)D in pregnant women are suitable as novel laboratory parameter for vitamin D status monitoring during human pregnancy and might replace in the future the routine total 25(OH)D assessment. KW - Measured free 25-hydroxyvitamin D KW - Calculated free 25-hydroxyvitamin D KW - Vitamin D-binding protein KW - Pregnancy KW - Reference intervals Y1 - 2018 U6 - https://doi.org/10.1016/j.jsbmb.2018.03.005 SN - 0960-0760 VL - 181 SP - 80 EP - 87 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Gilles, Maria A1 - Otto, Henrike A1 - Wolf, Isabell A. C. A1 - Scharnholz, Barbara A1 - Peus, Verena A1 - Schredl, Michael A1 - Suetterlin, Marc W. A1 - Witt, Stephanie H. A1 - Rietschel, Marcella A1 - Laucht, Manfred A1 - Deuschle, Michael T1 - Maternal hypothalamus-pituitary-adrenal (HPA) system activity and stress measures at birth JF - Psychoneuroendocrinology N2 - Background: Prenatal maternal stress might be a risk for the developing fetus and may have long-lasting effects on child and adult vulnerability to somatic and psychiatric disease. Over-exposure of the unborn to excess glucocorticoids and subsequent alteration of fetal development is hypothesized to be one of the key mechanisms linking prenatal stress with negative child outcome. Methods: In this prospective longitudinal study, mothers-to-be (n = 405) in late pregnancy (36.8 +/- 1.9 weeks of gestational age) and their singleton neonates were studied. We investigated the impact of different prenatal stress indices derived from six stress variables (perceived stress, specific prenatal worries, negative life events, symptoms of depression, trait anxiety, neuroticism) and diurnal maternal saliva cortisol secretion on gestational age and anthropometric measures at birth. KW - Early life stress KW - Gestational age KW - Anthropometric measures at birth KW - Cortisol KW - Prenatal distress KW - Pregnancy Y1 - 2018 U6 - https://doi.org/10.1016/j.psyneuen.2018.04.022 SN - 0306-4530 VL - 94 SP - 152 EP - 161 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Wolf, Isabell Ann-Cathrin A1 - Gilles, Maria A1 - Peus, Verena A1 - Scharnholz, Barbara A1 - Seibert, Julia A1 - Jennen-Steinmetz, Christine A1 - Krumm, Bertram A1 - Deuschle, Michael A1 - Laucht, Manfred T1 - Impact of prenatal stress on the dyadic behavior of mothers and their 6-month-old infants during a play situation: role of different dimensions of stress JF - Journal of neural transmission KW - Prenatal stress KW - Cortisol KW - Mother-infant behavior KW - Pregnancy KW - Stress inoculation Y1 - 2017 U6 - https://doi.org/10.1007/s00702-017-1770-3 SN - 0300-9564 SN - 1435-1463 VL - 124 SP - 1251 EP - 1260 PB - Springer CY - Wien ER - TY - JOUR A1 - Putra, Sulistyo Emantoko Dwi A1 - Neuber, Corinna A1 - Reichetzeder, Christoph A1 - Hocher, Berthold A1 - Kleuser, Burkhard T1 - Analysis of genomic DNA methylation levels in human placenta using liquid Chromatography-Electrospray ionization tandem mass spectrometry JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology N2 - Background: DNA-methylation is a common epigenetic tool which plays a crucial role in gene regulation and is essential for cell differentiation and embryonic development. The placenta is an important organ where gene activity can be regulated by epigenetic DNA modifications, including DNA methylation. This is of interest as, the placenta is the interface between the fetus and its environment, the mother. Exposure to environmental toxins and nutrition during pregnancy may alter DNA methylation of the placenta and subsequently placental function and as a result the phenotype of the offspring. The aim of this study was to develop a reliable method to quantify DNA methylation in large clinical studies. This will be a tool to analyze the degree of DNA methylation in the human placenta in relationship to clinical readouts. Methods: Liquid chromatography-electrospray ionization/multi-stage mass spectrometry (LC-ESI/MS/MS) technique was used for the quantification of the 5dmC/dG ratio in placentas from 248 healthy pregnancies. We were able to demonstrate that this method is a reliable and stable way to determine global placental DNA methylation in large clinical trials. Results/Conclusion: The degree of placental DNA methylation seen in our pilot study varies substantially from 2% to 5%. The clinical implications of this variation need to be demonstrated in adequately powered large studies. KW - Pregnancy KW - Placenta KW - Methylation KW - Global KW - LC-MS/MS KW - Fetal programming KW - Clinical Y1 - 2014 U6 - https://doi.org/10.1159/000358666 SN - 1015-8987 SN - 1421-9778 VL - 33 IS - 4 SP - 945 EP - 952 PB - Karger CY - Basel ER - TY - JOUR A1 - Pilari, Sabine A1 - Preusse, Cornelia A1 - Huisinga, Wilhelm T1 - Gestational influences on the pharmacokinetics of gestagenic drugs a combined in silico, in vitro and in vivo analysis JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, EUFEPS N2 - During preclinical development of a gestagenic drug, a significant increase of the total plasma concentration was observed after multiple dosing in pregnant rabbits, but not in (non-pregnant) rats or monkeys. We used a PBPK modeling approach in combination with in vitro and in vivo data to address the question to what extent the pharmacologically active free drug concentration is affected by pregnancy induced processes. In human, a significant increase in sex hormone binding globulin (SHBG), and an induction of hepatic CYP3A4 as well as plasma esterases is observed during pregnancy. We find that the observed increase in total plasma trough levels in rabbits can be explained as a combined result of (i) drug accumulation due to multiple dosing, (ii) increase of the binding protein SHBG, and (iii) clearance induction. For human, we predict that free drug concentrations in plasma would not increase during pregnancy above the steady state trough level for non-pregnant women. KW - PBPK KW - Pregnancy KW - Gestagenic drug KW - Protein binding KW - SHBG KW - Clearance induction Y1 - 2011 U6 - https://doi.org/10.1016/j.ejps.2010.12.003 SN - 0928-0987 VL - 42 IS - 4 SP - 318 EP - 331 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Li, Jian A1 - Chen, You-Peng A1 - Wang, Zi-Neng A1 - Liu, Tie-Bin A1 - Chen, Dan A1 - Dong, Yun-Peng A1 - Hocher, Berthold T1 - A functional fetal HSD11B2[CA]n microsatellite polymorphism is associated with maternal serum cortisol concentrations in pregnant women JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie N2 - Background/Aims: Cortisol plays an important role during pregnancy. It controls maternal glucose metabolism and fetal development. Cortisol metabolism is partially controlled by the 11b-HSD2. This enzyme is expressed in the kidney and human placenta. The activity of the enzyme is partially controlled by functional polymorphisms: the HSD11B2[CA]n microsatellite polymorphism. The impact of this functional gene polymorphism on cortisol metabolism and potential effects on the newborn's is unknown so far. Methods: In the current prospective birth cohort study in southern Asia, we analyzed the association of the HSD11B2[CA]n microsatellite polymorphisms in 187 mothers and their newborn's on maternal and newborn's serum cortisol concentrations. Results: Using multivariable regression analyses considering known confounding ( gestational age, newborn's gender, the labor uterine contraction states and the timing during the day of blood taking), we showed that the fetal HSD11B2[CA]n microsatellite polymorphisms in the first intron was related to maternal cortisol concentration ( R2=0.26, B=96.27, p=0.007), whereas as the newborn's cortisol concentrations were independent of fetal and maternal HSD11B2[CA] n microsatellite polymorphism. Conclusions: Our study showed for the first time that the fetal HSD11B2[CA]n microsatellite polymorphism of the HSD11B2 gene in healthy uncomplicated human pregnancy is associated with maternal cortisol concentration. This indicates that fetal genes controlling cortisol metabolism may affect maternal cortisol concentration and hence physiology in healthy pregnant women. KW - Pregnancy KW - Placenta KW - Cortisol vertical bar metabolism KW - 11 beta-hydroxysteroid dehydrogenase 2 KW - HSD11B2[CA]n polymorphism Y1 - 2013 U6 - https://doi.org/10.1159/000355761 SN - 1420-4096 SN - 1423-0143 VL - 38 IS - 1 SP - 132 EP - 141 PB - Karger CY - Basel ER -