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  • 1
    Online Resource
    Online Resource
    The bioavailability and maturing clearance of doxapram in preterm infants
    Springer Science and Business Media LLC ; 2021
    In:  Pediatric Research Vol. 89, No. 5 ( 2021-04), p. 1268-1277
    Details
    In: Pediatric Research, Springer Science and Business Media LLC, Vol. 89, No. 5 ( 2021-04), p. 1268-1277
    Type of Medium: Online Resource
    ISSN: 0031-3998 , 1530-0447
    URL: Article
    DOI: 10.1038/s41390-020-1037-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2031217-9
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Increasing Mean Arterial Blood Pressure and Heart Rate With Catecholaminergic Drugs Does Not Improve the Microcirculation in Children With Congenital Diaphragmatic Hernia : A Prospective Cohort Study
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Pediatric Critical Care Medicine Vol. 15, No. 4 ( 2014-05), p. 343-354
    Details
    In: Pediatric Critical Care Medicine, Ovid Technologies (Wolters Kluwer Health), Vol. 15, No. 4 ( 2014-05), p. 343-354
    Type of Medium: Online Resource
    ISSN: 1529-7535
    URL: Article
    DOI: 10.1097/PCC.0000000000000105
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 2070997-3
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  • 3
    Online Resource
    Online Resource
    UM206, a selective Frizzled antagonist, attenuates adverse remodeling after myocardial infarction in swine
    Elsevier BV ; 2016
    In:  Laboratory Investigation Vol. 96, No. 2 ( 2016-02), p. 168-176
    Details
    In: Laboratory Investigation, Elsevier BV, Vol. 96, No. 2 ( 2016-02), p. 168-176
    Type of Medium: Online Resource
    ISSN: 0023-6837
    URL: Article
    DOI: 10.1038/labinvest.2015.139
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 2041329-4
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  • 4
    Online Resource
    Online Resource
    Abstract 017: Effect of Sildenafil on Nitric Oxide-Mediated Vasodilation in the Human Placenta: an Ex-Vivo Placental Perfusion Study
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Hypertension Vol. 72, No. Suppl_1 ( 2018-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 72, No. Suppl_1 ( 2018-09)
    Abstract: Preeclampsia (PE) is a serious pregnancy complication characterized by suboptimal placentation, leading to increased vascular resistance and generalized endothelial dysfunction. A promising treatment is sildenafil, a phosphodiesterase-5 (PDE5) inhibitor that enhances nitric oxide (NO) mediated vasodilation. Although there are currently sildenafil trials ongoing in pregnant women, the effects of sildenafil on the placenta are still unknown. Placentas of healthy (n=17), early-onset (Eo)PE (n=6) and late-onset (Lo)PE (n=5) pregnancies were dually perfused, pre-constricted with serotonin, and subsequently exposed to the NO donor SNP in the absence or presence of 1 μmol/L sildenafil. Two healthy placentas were perfused with sildenafil on the maternal side to study placental transfer. Placental protein expression of PDE5, PDE1A, eNOS and iNOS was assessed using Western blot. Mean baseline pressure ±SEM was significantly lower (p 〈 0.05) in EoPE (22.3±2.8 mmHg) and LoPE (22.8±1.7 mmHg) vs. healthy placentas (33.1±2.2 mmHg). There was no effect of sildenafil on baseline pressure or serotonin-induced pre-constriction. Sildenafil tended to enhance vasodilatory response to 10 -6 M SNP in healthy (mean pressure decrease 4.3±0.8 vs. 8.1±1.9 mmHg, p=0.1) and LoPE placentas (3.0±1.0 vs. 7.3±3.2 mmHg), while no improvement was seen in EoPE placentas (6.0±2.0 vs. 5.0±1.0 mmHg). When sildenafil was added at the maternal side, average fetal-maternal concentration ratio was 0.22 after 3 hours of perfusion, as compared to 0.86 for antipyrine, a freely diffusing molecule. Placental levels of PDE1A tended to be higher in PE (p=0.08), while no differences in expression of PDE5, eNOS and iNOS were observed between PE and healthy placentas. Our study reveals that PE placentas have a significantly lower baseline pressure compared to healthy placentas, possibly due to lower resistance in the feto-placental vasculature as a compensation mechanism for the increased resistance in the spiral arteries. Although sildenafil tended to enhance vasodilation in healthy and LoPE placentas, it did not have those beneficial effects in EoPE. Possibly PDE1A-selective inhibitors should be applied in PE, or PDE is not the appropriate target for restoring disturbed vasodilation.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.72.suppl_1.017
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 2094210-2
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  • 5
    Online Resource
    Online Resource
    Influence of Maternal Angiogenic Factors During Pregnancy on Microvascular Structure in School-Age Children
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Hypertension Vol. 65, No. 4 ( 2015-04), p. 722-728
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 65, No. 4 ( 2015-04), p. 722-728
    Abstract: Reduced placental growth factor (PlGF) levels and higher soluble fms-like tyrosine kinase (sFlt-1) levels in mothers during pregnancy may have persistent effects on vascular structures in their offspring. We examined whether angiogenic factors during pregnancy also affect childhood retinal microvasculature in a population-based prospective cohort study among 3505 mothers and their children. We measured maternal PlGF and sFlt-1 in the first and second trimester of pregnancy. At the age of 6, we measured childhood retinal arteriolar and venular calibers from digitized retinal photographs. We performed multiple linear regression models, taking maternal and childhood sociodemographic and lifestyle-related characteristics, birth characteristics, and childhood current body mass index and blood pressure into account. We observed that first trimester maternal PlGF and sFlt-1 levels were not associated with childhood retinal arteriolar caliber. Lower second trimester maternal PlGF levels, but not sFlt-1 levels, were associated with narrower childhood retinal arteriolar caliber (difference: −0.09 SD score [95% confidence interval, −0.16 to 0.01], per SD score decrease in PlGF). This association was not explained by maternal and childhood sociodemographic and lifestyle-related characteristics, birth characteristics, or childhood current body mass index and blood pressure. Maternal PlGF and sFlt-1 levels in the first or second trimester were not associated with childhood retinal venular caliber. Our results suggest that lower maternal second trimester PlGF levels affect the microvascular development in the offspring, leading to narrower retinal arteriolar caliber in childhood. Further studies are needed to confirm these findings and to explore the underlying mechanisms and long-term cardiovascular consequences.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.114.05008
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2094210-2
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  • 6
    Online Resource
    Online Resource
    Transfer and Vascular Effect of Endothelin Receptor Antagonists in the Human Placenta
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Hypertension Vol. 75, No. 3 ( 2020-03), p. 877-884
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 75, No. 3 ( 2020-03), p. 877-884
    Abstract: Increasing evidence suggests a role for the ET (endothelin) system in preeclampsia. Hence, blocking this system with endothelin receptor antagonists (ERAs) could be a therapeutic strategy. Yet, clinical studies are lacking due to possible teratogenic effects of ERAs. In this study, we investigated the placental transfer of ERAs and their effect on ET-1-mediated vasoconstriction. Term placentas were dually perfused with the selective ET A R (ET type A receptor) antagonists sitaxentan and ambrisentan or the nonselective ET A R/ET B R antagonist macitentan and subsequently exposed to ET-1 in the fetal circulation. ET-1 concentration-response curves after incubation with sitaxentan, ambrisentan, macitentan, or the selective ET B R antagonist BQ-788 were also constructed in isolated chorionic plate arteries using wire-myography, and gene expression of the ET-system was quantified in healthy and early onset preeclamptic placentas. At steady state, the mean fetal-to-maternal transfer ratios were 0.32±0.05 for sitaxentan, 0.21±0.02 for ambrisentan, and 0.05±0.01 for macitentan. Except for BQ-788, all ERAs lowered the response to ET-1, both in the perfused cotyledon and isolated chorionic plate arteries. Placental gene expression of ECE-1, ET A R, and ET B R were comparable in healthy and preeclamptic placentas, while ET-1 expression was higher in preeclampsia. Our study is the first to show direct transfer of ERAs across the term human placenta. Furthermore, ET A R exclusively mediates ET-1-induced constriction in the fetoplacental vasculature. Given its limited transfer, macitentan could be considered as potential preeclampsia therapy. Extending knowledge on placental transfer to placentas of preeclamptic pregnancies is required to determine whether ERAs might be applied safely in preeclampsia.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.119.14183
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2094210-2
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  • 7
    Online Resource
    Online Resource
    Fetal and Infant Growth Patterns and Risk of Lower Lung Function and Asthma. The Generation R Study
    American Thoracic Society ; 2018
    In:  American Journal of Respiratory and Critical Care Medicine Vol. 197, No. 2 ( 2018-01-15), p. 183-192
    Details
    In: American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, Vol. 197, No. 2 ( 2018-01-15), p. 183-192
    Type of Medium: Online Resource
    ISSN: 1073-449X , 1535-4970
    URL: Article
    DOI: 10.1164/rccm.201703-0631OC
    RVK:
    XA 21200
    Language: English
    Publisher: American Thoracic Society
    Publication Date: 2018
    detail.hit.zdb_id: 1468352-0
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  • 8
    Online Resource
    Online Resource
    Preconception and early-pregnancy risk prediction for birth complications: development of prediction models within a population-based prospective cohort
    Springer Science and Business Media LLC ; 2022
    In:  BMC Pregnancy and Childbirth Vol. 22, No. 1 ( 2022-12)
    Details
    In: BMC Pregnancy and Childbirth, Springer Science and Business Media LLC, Vol. 22, No. 1 ( 2022-12)
    Abstract: Suboptimal maternal health already from preconception onwards is strongly linked to an increased risk of birth complications. To enable identification of women at risk of birth complications, we aimed to develop a prediction model for birth complications using maternal preconception socio-demographic, lifestyle, medical history and early-pregnancy clinical characteristics in a general population. Methods In a population-based prospective cohort study among 8340 women, we obtained information on 33 maternal characteristics at study enrolment in early-pregnancy. These characteristics covered the preconception period and first half of pregnancy ( 〈  21 weeks gestation). Preterm birth was 〈  37 weeks gestation. Small-for-gestational-age (SGA) and large-for-gestational-age (LGA) at birth were gestational-age-adjusted birthweight in the lowest or highest decile, respectively. Because of their co-occurrence, preterm birth and SGA were combined into a composite outcome. Results The basic preconception model included easy obtainable maternal characteristics in the preconception period including age, ethnicity, parity, body mass index and smoking. This basic preconception model had an area under the receiver operating characteristics curve (AUC) of 0.63 (95% confidence interval (CI) 0.61 to 0.65) and 0.64 (95% CI 0.62 to 0.66) for preterm birth/SGA and LGA, respectively. Further extension to more complex models by adding maternal socio-demographic, lifestyle, medical history and early-pregnancy clinical characteristics led to small, statistically significant improved models. The full model for prediction of preterm birth/SGA had an AUC 0.66 (95% CI 0.64 to 0.67) with a sensitivity of 22% at a 90% specificity. The full model for prediction of LGA had an AUC of 0.67 (95% CI 0.65 to 0.69) with sensitivity of 28% at a 90% specificity. The developed models had a reasonable level of calibration within highly different socio-economic subsets of our population and predictive performance for various secondary maternal, delivery and neonatal complications was better than for primary outcomes. Conclusions Prediction of birth complications is limited when using maternal preconception and early-pregnancy characteristics, which can easily be obtained in clinical practice. Further improvement of the developed models and subsequent external validation is needed.
    Type of Medium: Online Resource
    ISSN: 1471-2393
    URL: Article
    DOI: 10.1186/s12884-022-04497-2
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2059869-5
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  • 9
    Online Resource
    Online Resource
    Influence of genetic variants for birth weight on fetal growth and placental haemodynamics
    BMJ ; 2020
    In:  Archives of Disease in Childhood - Fetal and Neonatal Edition Vol. 105, No. 4 ( 2020-07), p. 393-398
    Details
    In: Archives of Disease in Childhood - Fetal and Neonatal Edition, BMJ, Vol. 105, No. 4 ( 2020-07), p. 393-398
    Abstract: To determine the combined effect of 60 genetic variants (single nucleotide polymorphisms, SNPs), previously identified as being associated with birth weight, on fetal growth and placental haemodynamics throughout pregnancy. Design Prospective birth cohort (Generation R Study). Setting General multiethnic population. Participants 5374 singleton liveborn children with genome-wide association arrays and fetal growth data. Methods Longitudinal and cross-sectional analyses of a genetic score of the total number of birth weight–increasing alleles across the 59 available SNPs and repeated fetal growth and haemodynamic measures. Main outcome measures SD scores (SDS) of fetal weight, (femur) length, head circumference, umbilical artery pulsatility index, uterine artery mean resistance index and placental weight, in different periods of pregnancy until birth. Results In longitudinal analyses, the effect of the genetic score on the fetal growth measures increased throughout pregnancy (p 〈 0.001). At 20 weeks of gestation, the genetic score was not associated with any of the fetal growth measures, whereas at 30 weeks it was associated with all. The strongest effects were observed at birth: per SD increase in genetic score, birth weight increased by 0.15 SDS (95% confidence interval: 0.13 to 0.18), birth length by 0.12 SDS (0.08 to 0.19) and head circumference by 0.08 SDS (0.05 to 0.12). The genetic score was not associated with placental haemodynamics, but was associated with a 14 g (10 to 18) increase in placental weight per SDS increase in genetic score. Conclusions Our results suggest that genetic variants related to birth weight exert their combined effect on fetal growth from second half of pregnancy onwards and have no effect on placental haemodynamics.
    Type of Medium: Online Resource
    ISSN: 1359-2998 , 1468-2052
    URL: Article
    DOI: 10.1136/archdischild-2019-317044
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2188490-0
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  • 10
    Online Resource
    Online Resource
    Predictive Intelligent Control of Oxygenation (PRICO) in preterm infants on high flow nasal cannula support: a randomised cross-over study
    BMJ ; 2021
    In:  Archives of Disease in Childhood - Fetal and Neonatal Edition Vol. 106, No. 6 ( 2021-11), p. 621-626
    Details
    In: Archives of Disease in Childhood - Fetal and Neonatal Edition, BMJ, Vol. 106, No. 6 ( 2021-11), p. 621-626
    Abstract: To investigate the efficacy of automated control of inspired oxygen (FiO2) by Predictive Intelligent Control of Oxygenation (PRICO) on the Fabian ventilator in maintaining oxygen saturation (SpO2) in preterm infants on high flow nasal cannula (HFNC) support. Design Single-centre randomised two-period crossover study. Setting Tertiary neonatal intensive care unit. Patients 27 preterm infants (gestational age (GA) 〈 30 weeks) on HFNC support with FiO2 〉 0.25. Intervention A 24-hour period on automated FiO2-control with PRICO compared with a 24-hour period on routine manual control (RMC) to maintain a SpO2 level within target range of 88%–95% measured at 30 s intervals. Main outcome measures Primary outcome: time spent within target range (88%–95%). Secondary outcomes: time spent above and below target range, in severe hypoxia (SpO2 〈 80%) and hyperoxia (SpO2 〉 98%), mean SpO2 and FiO2 and manual FiO2 adjustments. Results 15 patients received PRICO-RMC and 12 RMC-PRICO. The mean time within the target range increased with PRICO: 10.8% (95% CI 7.6 to 13.9). There was a decrease in time below target range: 7.6% (95% CI 4.2 to 11.0), above target range: 3.1% (95% CI 2.9 to 6.2) and in severe hypoxia: 0.9% (95% CI 1.5 to 0.2). We found no difference in time spent in severe hyperoxia. Mean FiO2 was higher during PRICO: 0.019 (95% CI 0.006 to 0.030). With PRICO there was a reduction of manual adjustments: 9/24 hours (95% CI 6 to 12). Conclusion In preterm infants on HFNC support, automated FiO2-control by PRICO is superior to RMC in maintaining SpO2 within target range. Further validation studies with a higher sample frequency and different ventilation modes are needed.
    Type of Medium: Online Resource
    ISSN: 1359-2998 , 1468-2052
    URL: Article
    DOI: 10.1136/archdischild-2020-320728
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2188490-0
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