Publications by authors named "Rolf Felix Maier"

9 Publications

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Detection of Volatile Organic Compounds as Potential Novel Biomarkers for Chorioamnionitis - Proof of Experimental Models.

Front Pediatr 2021 22;9:698489. Epub 2021 Jul 22.

Department of General Paediatrics and Neonatology, Saarland University Medical School, Homburg, Germany.

Histologic chorioamnionitis is only diagnosed postnatally which prevents interventions. We hypothesized that volatile organic compounds (VOCs) in the amniotic fluid might be useful biomarkers for chorioamnionitis and that VOC profiles differ between amnionitis of different origins. Time-mated ewes received intra-amniotic injections of media or saline (controls), or live serovar 3 (Up) 14, 7 or 3d prior to c-section at day 124 gestational age (GA). 100 μg recombinant ovine IL-1α was instilled at 7, 3 or 1d prior to delivery. Headspace VOC profiles were measured from amniotic fluids at birth using ion mobility spectrometer coupled with multi-capillary columns. 127 VOC peaks were identified. 27 VOCs differed between samples from controls and Up- or IL-1α induced amnionitis. The best discrimination between amnionitis by Up vs. IL-1α was reached by 2-methylpentane, with a sensitivity/specificity of 96/95% and a positive predictive value/negative predictive values of 96 and 95%. The concentration of 2-methylpentane in VOCs peaked 7d after intra-amniotic instillation of Up. We established a novel method to study headspace VOC profiles of amniotic fluids. VOC profiles may be a useful tool to detect and to assess the duration of amnionitis induced by Up. 2-methylpentane was previously described in the exhalate of women with pre-eclampsia and might be a volatile biomarker for amnionitis. Amniotic fluids analyzed by ion mobility spectrometry coupled with multi-capillary columns may provide bedside diagnosis of amnionitis and understanding inflammatory mechanisms during pregnancy.
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http://dx.doi.org/10.3389/fped.2021.698489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339372PMC
July 2021

Association between postnatal growth and neurodevelopmental impairment by sex at 2 years of corrected age in a multi-national cohort of very preterm children.

Clin Nutr 2021 08 15;40(8):4948-4955. Epub 2021 Jul 15.

Université de Paris, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, INSERM, INRA, F-75004, Paris, France.

Background & Aims: Extra-uterine growth restriction (EUGR) is common among very preterm (VPT) infants and has been associated with impaired neurodevelopment. Some research suggests that adverse effects of EUGR may be more severe in boys. We investigated EUGR and neurodevelopment at 2 years of corrected age (CA) by sex in a VPT birth cohort.

Methods: Data come from a population-based cohort of children born <32 weeks' gestation from 11 European countries and followed up at 2 years CA. Postnatal growth during the neonatal hospitalization was measured with: (1) birthweight and discharge-weight Z-score differences using Fenton charts (2) weight-gain velocity using Patel's model. Published cut-offs were used to define EUGR as none, moderate or severe. Neurodevelopmental impairment was assessed using a parent-report questionnaire, with standardized questions/instruments on motor function, vision, hearing and non-verbal cognition. We estimated relative risks (RR) adjusting for maternal and neonatal characteristics overall and by sex.

Results: Among 4197 infants, the prevalence of moderate to severe impairment at 2 years CA was 17.7%. Severe EUGR was associated with neurodevelopmental impairment in the overall sample and the interaction with sex was significant. For boys, adjusted RR were 1.57 (95% Confidence Intervals (CI): 1.18-2.09) for Fenton's delta Z-score and 1.50 (95% CI: 1.12-2.01) for Patel's weight-gain velocity, while for girls they were 0.97 (0.76-1.22) and 1.12 (0.90-1.40) respectively.

Conclusion: EUGR was associated with poor neurodevelopment at 2 years among VPT boys but not girls. Understanding why boys are more susceptible to the effects of poor growth is needed to develop appropriate healthcare strategies.
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http://dx.doi.org/10.1016/j.clnu.2021.07.005DOI Listing
August 2021

Different Effects of Two Protocols for Pre-Procedural Analgosedation on Vital Signs in Neonates during and after Endotracheal Intubation.

Klin Padiatr 2021 Jul 19;233(4):181-188. Epub 2021 Jan 19.

Children's hospital, Philipps University Marburg Faculty of Medicine, Marburg, Germany.

Background: Analgosedation is often used for endotracheal intubation in neonates, but no consensus exists on the optimal pre-procedural medication.

Aims: To compare the time to intubation and vital signs during and after intubation in 2 NICUs using different premedication protocols.

Methods: Prospective observational study in 2 tertiary NICUs, comparing fentanyl and optional vecuronium for elective neonatal endotracheal intubation (NICU-1) with atropine, morphine, midazolam and optional pancuronium (NICU-2). Primary endpoints were: time to intubate and number of intubation attempts; secondary endpoints were: deviations of heart rate, oxygen saturation and blood pressure from baseline until 20 min post intubation.

Results: 45 and 30 intubations were analyzed in NICU-1 and NICU-2. Time to intubation was longer in NICU-1 (7 min) than in NICU-2 (4 min; p=0.029), but the mean number of intubation attempts did not differ significantly. Bradycardias (34 vs. 1, p<0.001) and hypoxemias (136 vs. 48, p<0.001) were more frequent in NICU-1, and tachycardias (59 vs. 72, p<0.001) more frequent in NICU-2. Mean arterial blood pressure (MAP) increased in NICU-1 (+6.18 mmHg) and decreased in NICU-2 (-5.83 mmHg), whereas mean heart rates (HR) decreased in NICU-1 (-19.29 bpm) and increased in NICU-2 (+15.93 bpm). MAP and HR returned to baseline 6-10 min after intubation in NICU-1 and after 11-15 min and 16-20 min in NICU-2, respectively.

Conclusions: The two protocols yielded significant differences in the time to intubation and in the extent and duration of physiologic changes during and post-intubation. Short acting drugs should be preferred and vital signs should be closely monitored at least 20 min post intubation. More studies are required to identify analgosedation protocols that minimize potentially harmful events during endotracheal intubation.
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http://dx.doi.org/10.1055/a-1330-8538DOI Listing
July 2021

Variation in very preterm extrauterine growth in a European multicountry cohort.

Arch Dis Child Fetal Neonatal Ed 2021 May 2;106(3):316-323. Epub 2020 Dec 2.

Université de Paris, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team,EPOPé, INSERM, INRA, F-75004, Paris, France.

Objective: Extrauterine growth restriction (EUGR) among very preterm infants is related to poor neurodevelopment, but lack of consensus on EUGR measurement constrains international research. Our aim was to compare EUGR prevalence in a European very preterm cohort using commonly used measures.

Design: Population-based observational study.

Setting: 19 regions in 11 European countries.

Patients: 6792 very preterm infants born before 32 weeks' gestational age (GA) surviving to discharge.

Main Outcome Measures: We investigated two measures based on discharge-weight percentiles with (1) Fenton and (2) Intergrowth (IG) charts and two based on growth velocity (1) birth weight and discharge-weight Z-score differences using Fenton charts and (2) weight-gain velocity using Patel's model. We estimated country-level relative risks of EUGR adjusting for maternal and neonatal characteristics and associations with population differences in healthy newborn size, measured by mean national birth weight at 40 weeks' GA.

Results: About twofold differences in EUGR prevalence were observed between countries for all indicators and these persisted after case-mix adjustment. Discharge weight <10th percentile using Fenton charts varied from 24% (Sweden) to 60% (Portugal) and using IG from 13% (Sweden) to 43% (Portugal), while low weight-gain velocity ranged from 35% (Germany) to 62% (UK). Mean term birth weight strongly correlated with both percentile-based measures (Spearman's rho=-0.90 Fenton, -0.84 IG, p<0.01), but not Patel's weight-gain velocity (rho: -0.38, p=0.25).

Conclusions: Very preterm infants have a high prevalence of EUGR, with wide variations between countries in Europe. Variability associated with mean term birth weight when using common postnatal growth charts complicates international benchmarking.
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http://dx.doi.org/10.1136/archdischild-2020-319946DOI Listing
May 2021

[Kidney Cysts and Cystic Nephropathies in Children - A Consensus Guideline by 10 German Medical Societies].

Klin Padiatr 2020 Sep 13;232(5):228-248. Epub 2020 Jul 13.

Center for Pediatrics and Adolescent Medicine, Division of Pediatric Nephrology, University Hospital Heidelberg, Heidelberg.

This consensus-based guideline was developed by all relevant German pediatric medical societies. Ultrasound is the standard imaging modality for pre- and postnatal kidney cysts and should also exclude extrarenal manifestations in the abdomen and internal genital organs. MRI has selected indications. Suspicion of a cystic kidney disease should prompt consultation of a pediatric nephrologist. Prenatal management must be tailored to very different degrees of disease severity. After renal oligohydramnios, we recommend delivery in a perinatal center. Neonates should not be denied renal replacement therapy solely because of their age. Children with unilateral multicystic dysplastic kidney do not require routine further imaging or nephrectomy, but long-term nephrology follow-up (as do children with uni- or bilateral kidney hypo-/dysplasia with cysts). ARPKD (autosomal recessive polycystic kidney disease), nephronophthisis, Bardet-Biedl syndrome and HNF1B mutations cause relevant extrarenal disease and genetic testing is advisable. Children with tuberous sclerosis complex, tumor predisposition (e. g. von Hippel Lindau syndrome) or high risk of acquired kidney cysts should have regular ultrasounds. Even asymptomatic children of parents with ADPKD (autosomal dominant PKD) should be monitored for hypertension and proteinuria. Presymptomatic diagnostic ultrasound or genetic examination for ADPKD in minors should only be done after thorough counselling. Simple cysts are very rare in children and ADPKD in a parent should be excluded. Complex renal cysts require further investigation.
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http://dx.doi.org/10.1055/a-1179-0728DOI Listing
September 2020

T17 Cell Frequency in Peripheral Blood Is Elevated in Overweight Children without Chronic Inflammatory Diseases.

Front Immunol 2017 16;8:1543. Epub 2017 Nov 16.

Children's Hospital, Philipps University, Marburg, Germany.

Background: The prevalence of obesity has dramatically increased in children in the last few decades and is associated with chronic inflammatory diseases. Fat tissue produces IL-6 and TNF-α, which are stimuli for T17 cell differentiation. These cells are characterized by expression of the transcription factor receptor-related orphan receptor C (RORC) and by IL-17A production. In murine models, obesity has been linked with elevated T17 cell frequencies. The aim of this study was to explore whether being overweight was associated with an elevated frequency of circulating T17 cells or elevated messenger RNA (mRNA)-levels of IL-17A and RORC in children without chronic inflammatory diseases.

Methods: We studied peripheral blood samples from 15 overweight and 50 non-overweight children without a history of autoimmune diseases, asthma, atopic dermatitis or allergic rhinoconjunctivitis. T17 cells were quantified in Ionomycin stimulated peripheral blood mononuclear cells by flow cytometry using intracellular IL-17A staining. RORC- and IL-17A expressions were measured by real-time PCR.

Results: We found significantly elevated T cell frequencies in overweight children compared then on-overweight controls with 34.7 ± 1.5% of CD3CD4 cells versus 25.4 ± 2.4% (mean ± SEM,  = 0.0023), respectively. Moreover, T cell frequencies correlated positively with body mass index ( = 0.42,  = 0.0005, respectively). The relative mRNA expression of RORC ( = 0.013) and IL-17A ( = 0.014) were upregulated in overweight compared to non-overweight children.

Conclusion: Childhood obesity is an independent factor that is associated with an elevated frequency of circulating T17 cells and higher expression of RORC- and IL-17A-mRNA after stimulation with Ionomycin. This might be due to the inflammatory activity of the fat tissue. Studies on T17 immunity should not only be adjusted for acute and chronic inflammatory diseases but also for overweight.
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http://dx.doi.org/10.3389/fimmu.2017.01543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696328PMC
November 2017
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