Publications by authors named "Bernd Beedgen"

10 Publications

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Case Report: Successful Long-Term Management of a Low-Birth Weight Preterm Infant With Compound Heterozygous Protein C Deficiency With Subcutaneous Protein C Concentrate Up to Adolescence.

Front Pediatr 2021 28;9:591052. Epub 2021 Sep 28.

Department of Neonatology, Heidelberg University Children's Hospital, Heidelberg, Germany.

Homozygous/compound heterozygous forms of congenital protein C deficiency are often associated with severe antenatal and postnatal thrombotic or hemorrhagic complications. Protein C deficiency frequently leads to severe adverse outcomes like blindness and neurodevelopmental delay in children and may even lead to death. The most widely used long-term postnatal treatment consists of oral anticoagulation with vitamin K antagonists (e.g., warfarin), which is supplemented with protein C concentrate in acute phases. Subcutaneous infusions have been described in infants mostly from 2 months of age after severe postnatal thrombosis, but not in newborns or premature infants without thromboembolism. We report the first case of a compound heterozygous protein C-deficient preterm infant, born at 31+5 weeks of gestation to parents with heterozygous protein C deficiency (protein C activity 0.9% at birth). We focus on both prenatal and perinatal management including antithrombotic treatment during pregnancy, the cesarean section, and continuous postnatal intravenous and consecutive subcutaneous therapy with protein C concentrate followed by a change of therapy to direct oral anticoagulants (DOACs) (apixaban). We report successful home treatment with subcutaneous protein C concentrate substitution overnight (target protein C activity >25%) without complication up to 12.5 years of age. We propose that early planned cesarean section at 32 or preferably 34 weeks of gestation limits potential maternal side effects of anticoagulation with vitamin K antagonists and reduces fetal thromboembolic complications during late pregnancy. Intravenously administered protein C and early switch to subcutaneous infusions (reaching about 3 kg body weight) resulted in sufficient protein C activity and has guaranteed an excellent quality of life without any history of thrombosis for 13 years now. In older children with protein C deficiency, as in our case, DOACs could be a new therapeutic option.
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http://dx.doi.org/10.3389/fped.2021.591052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506145PMC
September 2021

Urinary acute kidney injury biomarkers in very low-birth-weight infants on indomethacin for patent ductus arteriosus.

Pediatr Res 2019 04 11;85(5):678-686. Epub 2019 Feb 11.

Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.

Background: Serum creatinine (SCr)- or urine output-based definitions of acute kidney injury (AKI) have important limitations in neonates. This study evaluates the diagnostic value of urinary biomarkers in very low-birth-weight (VLBW) infants receiving indomethacin for closure of a patent ductus arteriosus (PDA).

Methods: Prospective cohort study in 14 indomethacin-treated VLBW infants and 18 VLBW infants without indomethacin as controls. Urinary biomarkers were measured before, during, and after indomethacin administration.

Results: Indomethacin therapy was associated with significantly higher SCr concentrations at 36, 84, and 120 h compared to controls. At 36 h, three indomethacin-treated patients met the criteria for neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) AKI. The product of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]•[IGFBP7]) was significantly elevated in the AKI subgroup at 12 h (P < 0.05), hence 24 h earlier than the increase in SCr. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin were significantly increased in the indomethacin group at 12 h (P < 0.05), irrespective of fulfillment of the AKI criteria. Urinary kidney injury molecule-1 (KIM-1) was not significantly altered.

Conclusion: While urinary [TIMP-2]•[IGFBP7] proves valuable for the early diagnosis of neonatal modified KDIGO-defined AKI, elevated urinary NGAL and calprotectin concentrations in indomethacin-treated VLBW infants not fulfilling the AKI criteria may indicate subclinical kidney injury.
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http://dx.doi.org/10.1038/s41390-019-0332-9DOI Listing
April 2019

Immunotherapy with ipilimumab plus nivolumab in a stage IV melanoma patient during pregnancy.

Eur J Cancer 2018 11 25;104:239-242. Epub 2018 Oct 25.

Department of Dermatology, Section of DermatoOncology, National Center for Tumor Diseases (NCT), University of Heidelberg, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.ejca.2018.09.008DOI Listing
November 2018

Prophylactic administration of surfactant in extremely premature infants.

Crit Care Res Pract 2010 7;2010. Epub 2010 Jun 7.

Division of Neonatology, Department of Pediatrics, University of Heidelberg Medical School, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany.

Objective. To investigate whether prophylactic surfactant administration is superior over selective treatment in preterm infants with respiratory distress syndrome (RDS). Methods. In our retrospective analysis, we compared premature infants (23 + 0 to 26 + 6 weeks) receiving 200 mg/kg surfactant (curosurf(®)) within five minutes after birth (prophylactic group, N = 31) with those infants who received surfactant therapy for established RDS (selective group, N = 34). Results. Prophylactic therapy significantly decreased the need for mechanical ventilation (74 hours per patient versus 171 hours per patient, resp.). We observed a reduced incidence of interstitial emphysema (0% versus 9%, resp.), pneumothoraces (3% versus 9%, resp.), chronic lung disease (26% versus 38%, resp.), and surfactant doses per patient (1.3 versus 1.8, resp.), although those variables did not reach significance. Conclusion. We conclude that infants under 27 weeks' gestation profit from prophylactic surfactant administration by reducing the time of mechanical ventilation. This in turn could contribute to reduce the risk for mechanical ventilation associated complications, without any detrimental short-term side effects.
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http://dx.doi.org/10.1155/2010/235894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2951078PMC
July 2011

Intracerebellar hemorrhage in premature infants: sonographic detection and outcome.

J Perinat Med 2007 ;35(1):67-70

Division of Neonatology, Department of Pediatrics, University of Heidelberg, Germany.

Aims: Intracerebellar hemorrhage is a rarely confirmed diagnosis in preterm infants in comparison to peri-/intraventricular hemorrhage. This study evaluates the incidence of intracerebellar hemorrhage and neurological outcome in preterm infants.

Methods: 260 infants with gestational age of 22-32 weeks were studied prospectively by cranial ultrasound. Neurodevelopmental outcome was examined in the first three years of life.

Results: 15 infants had intracranial hemorrhage grade II-IV (10 intraventricular, 6 intracerebellar hemorrhage). Neurodevelopmental follow-up showed that one infant with intracerebellar hemorrhage is severely handicapped, two have moderate and two mild impairments and one has no sequelae.

Conclusion: Cerebellar hemorrhage is not rare if ultrasound examination is specifically focused on cerebellar lesions.
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http://dx.doi.org/10.1515/JPM.2007.010DOI Listing
April 2007

Pharmacokinetics of a netilmicin loading dose on the first postnatal day in preterm neonates with very low gestational age.

Eur J Clin Pharmacol 2006 Sep 25;62(9):773-7. Epub 2006 Jul 25.

Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany.

Objective: Pharmacokinetic parameters are important for dose adjustment of aminoglycosides, but they are highly variable in neonates. In this study the pharmacokinetics of a netilmicin loading dose was investigated on the first postnatal day in preterm neonates with very low gestational age (GA).

Methods: In an open prospective study, 20 neonates with GA between 22.9 and 32.0 weeks and suspected postnatal bacterial infection received an intravenous loading dose of 5 mg/kg netilmicin over 1 h during the first postnatal day. Netilmicin serum concentrations were determined by an enzyme multiplied immunoassay.

Results: The systemic clearance of netilmicin normalized to body weight (BW) was not significantly different in three GA subgroups (0.59+/- 0.02 ml/min/kg for GA <24 weeks, 0.72+/-0.14 ml/min/kg for GA 24-27 weeks, and 0.62+/-0.19 ml/min/kg for GA 27-32 weeks, P=0.123). Similar results were also obtained for serum elimination half-time and for the distribution volume normalized to BW. Multiple regression analysis showed that systemic clearance and volume of distribution (both not normalized to BW) significantly correlated with BW (P<0.0001) but not with GA. In the entire group, 20% of peak concentrations were below the target of 6 mg/l, and 63% of trough concentrations were above the target of 2 mg/l.

Conclusion: In neonates with very low GA, the pharmacokinetic parameters of netilmicin determined after an intravenous loading dose were not dependent on GA when normalized to BW. A number of neonates did not reach targeted peak and trough netilmicin serum concentrations, suggesting that a higher loading dose and a prolonged dosing interval might enhance the effectiveness and safety of netilmicin in preterm neonates immediately after birth.
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http://dx.doi.org/10.1007/s00228-006-0153-8DOI Listing
September 2006

Effectiveness and side effects of an escalating, stepwise approach to indomethacin treatment for symptomatic patent ductus arteriosus in premature infants below 33 weeks of gestation.

Pediatrics 2005 Dec;116(6):1361-6

Division of Neonatology, Department of Pediatrics, University of Heidelberg, Heidelberg, Germany.

Objective: Symptomatic patent ductus arteriosus (sPDA) is a common problem in premature infants and can be treated effectively with intravenous indomethacin, leading to permanent ductal closure in 70% to 80% of infants. Infants who do not respond to pharmacologic closure of the duct ultimately have to undergo surgical or interventional closure of the PDA. Optimizing the pharmacologic treatment could offer an interesting approach to reduce the number of infants who need surgical closure of the duct.

Methods: We conducted a retrospective analysis in infants who were <33 weeks' gestation, had sPDA, and were treated with high-dose intravenous indomethacin. From 1993 to 2002, 129 infants with sPDA received indomethacin after diagnosis of sPDA was confirmed by echocardiography. Treatment was started in all infants with intravenous indomethacin (0.2 mg/kg given 5 times at 0 hours, 12 hours, 24 hours, 48 hours, and 72 hours). When the ductus was still open at 36 hours, indomethacin every 12 hours was continued and single doses increased up to 1 mg/kg until ductal closure was achieved.

Results: In 68 (53%) of 129 infants who were treated with indomethacin, ductal closure occurred during intermediate-dose indomethacin therapy (up to 1.5 mg/kg total dose). In the 61 initial nonresponders, the continuation of indomethacin led to ductal closure in 59 infants. When infants who were treated with an intermediate dose were compared with the initial nonresponders, no differences in the incidences of renal or electrolyte abnormalities, gastrointestinal bleeding, intraventricular hemorrhage, or periventricular leukomalacia were found.

Conclusions: High-dose indomethacin after intermediate-dose therapy resulted in an overall closure rate of 98.5% (127 of 129). Although single indomethacin doses of up to 1 mg/kg were given, high-dose indomethacin was safe.
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http://dx.doi.org/10.1542/peds.2005-0293DOI Listing
December 2005

Energy expenditure in neonates with Down syndrome.

J Pediatr 2003 Aug;143(2):264-6

Division of Neonatology, Department of Pediatrics, University of Heidelberg, Im Neuenheimer Feld 150, D-69120 Heidelberg, Germany.

Resting energy expenditure was measured in term neonates with Down syndrome during the first week of life and compared with healthy neonates. Infants with Down syndrome expended 14% fewer calories than did healthy infants of the same age.
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http://dx.doi.org/10.1067/S0022-3476(03)00327-5DOI Listing
August 2003

Six day antimicrobial therapy for early-onset group B streptococcal infection in near-term and term neonates.

Scand J Infect Dis 2003 ;35(5):302-5

Department of Pediatrics, Division of Neonatology, University of Heidelberg, Heidelberg, Germany.

Antibiotics for the treatment of group B streptococcal (GBS) infection are usually given for 7-10 d. The aim of this prospective investigation was to study whether antibiotic treatment for 6 d is sufficient to treat early-onset GBS infection in term and near-term neonates. During a 2 y period 67 neonates of GBS-positive mothers developed GBS infection and were admitted to the neonatal intensive care unit. All neonates showed clinical signs of infection, C-reactive protein levels > 20 mg/l and/or elevated immature to total neutrophil ratio > 0.25. Two groups were differentiated: 10 neonates with proven sepsis with GBS-positive blood cultures (15%) and 57 neonates with presumed GBS infection with negative blood cultures but with GBS-positive surface swab cultures of ear (68%), nasopharyngeal (21%) or gastric aspirate (16%). All patients were GBS positive in 1 or more cultures. Antimicrobial therapy with ampicillin and cefotaxime was discontinued after 6 d. At that time all neonates were asymptomatic and laboratory results were normal. No relapse or death within 4 weeks after therapy was detected. In conclusion, antibiotic therapy for 6 d was sufficient to treat 10 neonates with proven and 57 neonates with presumed early-onset GBS infection. Owing to the small sample size, further studies are needed to show significant differences to longer therapy regimens.
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http://dx.doi.org/10.1080/00365540310008438DOI Listing
September 2003

Caffeine impairs cerebral and intestinal blood flow velocity in preterm infants.

Pediatrics 2002 May;109(5):784-7

Department of Paediatrics, Division of Neonatology, University of Heidelberg, Heidelberg, Germany.

Objective: In adults, a single dose of 250 mg of caffeine may decrease cerebral blood flow by 30%. In preterm infants, caffeine is commonly used for the treatment and prophylaxis of apnea. The purpose of this investigation was to assess effects of caffeine on circulatory parameters in preterm infants.

Methods: We studied 16 preterm neonates with a mean gestational age (mean +/- standard deviation) of 31 +/- 1.2 weeks (range: 29-33 weeks), birth weight of 1400 +/- 380 g (range: 625-2060 g), and postnatal age of 24 to 72 hours before and 1 and 2 hours after an oral loading dose of 25 mg/kg pure caffeine. We investigated left ventricular output (LVO), cerebral blood flow velocity (BFV) of the internal carotid artery (ICA) and the anterior cerebral artery, and intestinal BFV of the celiac artery and superior mesenteric artery by Doppler sonography.

Results: Mean BFV in the ICA decreased significantly 1 (17%) and 2 hours (22%) after caffeine administration. Mean BFV in the anterior cerebral artery showed a reduction of 14% after 2 hours. The mean BFV in the superior mesenteric artery decreased significantly 1 and 2 hours after caffeine administration (30%). Mean BFV in the celiac artery showed a significant reduction of 14% 1 hour after caffeine. No changes were observed in LVO, blood pressure, and heart rate.

Conclusion: Oral administration of a high loading dose of caffeine results in marked reduction of cerebral and intestinal BFV, without changing LVO, blood pressure, and heart rate.
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http://dx.doi.org/10.1542/peds.109.5.784DOI Listing
May 2002
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