Fatal congenital copper transport defect caused by a homozygous likely pathogenic variant of SLC31A1.

Known hereditary human diseases featuring impaired copper trafficking across cellular membranes involve ATP7A (Menkes disease, occipital horn disease, X-linked spinal muscular atrophy type 3) and ATP7B (Wilson disease). Herein, we report a newborn infant of consanguineous parents with a homozygous pathogenic variant in a highly conserved sequence of SLC31A1, coding for the copper influx transporter 1, CTR1. This missense variant, c.236T > C, was detected by whole exome sequencing. The infant was born with pulmonary hypoplasia and suffered from severe respiratory distress immediately after birth, necessitating aggressive mechanical ventilation. At 2 weeks of age, multifocal brain hemorrhages were diagnosed by cerebral ultrasound and magnetic resonance imaging, together with increased tortuosity of cerebral arteries. Ensuing seizures were only partly controlled by antiepileptic drugs, and the infant became progressively comatose. Laboratory investigations revealed very low serum concentrations of copper and ceruloplasmin. No hair shaft abnormalities were detected by dermatoscopy or light microscopic analyses of embedded hair shafts obtained at 4 weeks of life. The infant died after redirection of care and elective cessation of invasive mechanical ventilation at 1 month of age. This case adds SLC31A1 to the genes implicated in severe hereditary disorders of copper transport in humans.

Plötzlicher Kindstod von zwei Säuglingen in Babytragehilfen.

Sudden unexpected death in infancy (SUDI), previously termed sudden infant death syndrome (SIDS), is the second leading cause of death in infants beyond the neonatal period in Germany, and a major cause of infant mortality in economically well developed countries (OECD Health Statistics, 2019). The risk of SUDI peaks at the age of 2-4 months and then decreases continuously till the end of the first year. A complex multifactorial cause, rather than a single characteristic factor, may cause SUDI within a critical period of infant development (Guntheroth WG et al., Pediatrics 2002; 110: e64-e64). Risk factors include prematurity, male gender, bottle-feeding, prone sleeping position, overheating, as well as exposure to smoke amongst others (Carpenter RG et al., Lancet 2004; 363: 185-191). Thus, health professionals consistently advise and educate parents about avoidable risk factors of SUDI at routine well-baby examinations. Since the advent of SUDI prevention strategies in the 1980s, the incidence has decreased 10fold, from 1,55/1.000 live births in 1991 to 0,15/1000 in 2015. This number seems to have reached a steady state (Statistisches Bundesamt Germany, 2015).

The circadian clock regulates rhythmic erythropoietin expression in the murine kidney.

Generation of circadian rhythms is cell-autonomous and relies on a transcription/translation feedback loop controlled by a family of circadian clock transcription factor activators including CLOCK, BMAL1 and repressors such as CRY1 and CRY2. The aim of the present study was to examine both the molecular mechanism and the hemopoietic implication of circadian erythropoietin expression. Mutant mice with homozygous deletion of the core circadian clock genes cryptochromes 1 and 2 (Cry-null) were used to elucidate circadian erythropoietin regulation. Wild-type control mice exhibited a significant difference in kidney erythropoietin mRNA expression between circadian times 06 and 18. In parallel, a significantly higher number of erythropoietin-producing cells in the kidney (by RNAscope®) and significantly higher levels of circulating erythropoietin protein (by ELISA) were detected at circadian time 18. Such changes were abolished in Cry-null mice and were independent from oxygen tension, oxygen saturation, or expression of hypoxia-inducible factor 2 alpha, indicating that circadian erythropoietin expression is transcriptionally regulated by CRY1 and CRY2. Reporter gene assays showed that the CLOCK/BMAL1 heterodimer activated an E-box element in the 5' erythropoietin promoter. RNAscope® in situ hybridization confirmed the presence of Bmal1 in erythropoietin-producing cells of the kidney. In Cry-null mice, a significantly reduced number of reticulocytes was found while erythrocyte numbers and hematocrit were unchanged. Thus, circadian erythropoietin regulation in the normoxic adult murine kidney is transcriptionally controlled by master circadian activators CLOCK/BMAL1, and repressors CRY1/CRY2. These findings may have implications for kidney physiology and disease, laboratory diagnostics, and anemia therapy.

Epidemiology of Sepsis Among Children and Neonates in Germany: Results From an Observational Study Based on Nationwide Diagnosis-Related Groups Data Between 2010 and 2016.

OBJECTIVES: Worldwide, more than half of all sepsis cases occur in pediatric and adolescent patients, particularly in neonates. Previous population-based studies in these age groups often were limited to either neonatal or pediatric patients admitted to ICUs. We aimed to investigate the overall and age-specific incidence and case fatality of sepsis in children in Germany, a high-income country with a total population of 82 million. DESIGN: Retrospective observational study based on the German Diagnosis-related Groups statistics of the years 2010-2016. SETTING: All acute care hospitals in Germany except for prison and psychiatric hospitals. PATIENTS: Pediatric patients less than or equal to 19 years with International Classification of Diseases, 10th Revision-coded sepsis, neonates with International Classification of Diseases, 10th Revision-coded neonatal sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed pediatric sepsis incidence in patients aged birth to less than or equal to 19 years old, case fatality, and underlying comorbidities, and neonatal sepsis incidence and case fatality within the neonatal period. We identified 14,635 pediatric sepsis cases among 15.4 million pediatric hospitalizations between 2010 and 2016 (= 0.1% of pediatric hospitalizations). The incidence of pediatric sepsis was 14 cases per 100,000 children between 0 and 19 years. Case fatality was 16.6% and decreased from 17.8% (2010) to 15.0% (2016). A total of 11.5% of hospital deaths in the age group 0-19 years were associated with pediatric sepsis. Sepsis incidence and case fatality were highest in children less than 1 year old and declined in older children and adolescents. Admissions with pediatric sepsis were more common in children with preexisting comorbidities compared with those without (0.52% vs 0.03% of pediatric admissions). In neonates, the incidence of neonatal sepsis was 1,006 cases per 100,000 live births. Case fatality was 3.9%. While 17.7% of very low birth weight infants had neonatal sepsis, only 2.1% of low birth weight and 0.6% of normal birth weight neonates were affected, respectively. CONCLUSIONS: Sepsis is also in Germany a common and frequently fatal condition in pediatric patients, particularly among neonates and children with comorbidities.

Adult Donor Blood Products as Risk Factors for Central Venous Catheter-associated Thromboembolism in Neonates: A Retrospective Case-Control Study.

This study aimed to examine whether the transfusion of donor blood products, abnormal coagulation or inflammation increase the risk of venous thromboembolism (VTE) associated with central venous catheters (CVC) in neonates. A retrospective case-control study including 25 neonates with CVC-associated VTE and tightly matched controls with CVC, but without VTE was performed. The frequency of (i) abnormal coagulation screens, (ii) increased inflammatory marker proteins before catheter insertion, or (iii) catheter-associated blood stream infection did not differ between cases and controls. No difference was found in the number or type of transfusions within the last day before VTE. However, the total number of transfusions in the time period between catheter placement and VTE diagnosis (median 6.5 d) was significantly higher (P<0.001) in cases (44 red blood cell, 61 plasma, and 18 platelet transfusions) compared with an equal median time period of 7 days postcatheter insertion in controls (26/24/11). In conclusion, intensive transfusion treatment (through a peripheral line) after CVC insertion was associated with a higher risk of VTE (odds ratio 7.58; 95% confidence interval, 0.84-68.46), suggesting that transfusion of adult donor blood products into the cellular and plasmatic hemostatic system of the neonate increases the risk for CVC-associated VTE.

[Consequences of the SARS-CoV-2 Pandemia on the Early Childhood Examinations]. / Auswirkungen der SARS-CoV-2 Pandemie auf die Früherkennungs-Untersuchungen bei Kindern.

Seit Mitte Mai wird berichtet, dass die Maßnahmen oder die Angst vor einer Infektion mit SARS-CoV-2 zu einem sekundären Gesundheitsrisiko führen könnten, weil Diagnosen, z. B. von Krebs- oder Herz-Kreislauferkrankungen, verspätet gestellt und Therapien, z. B. komplizierte operative Eingriffe mit Intensivpflege, verzögert durchgeführt werden (COVIDSurg Collaborative, Br J Surg 2020; DOI: 10.1002/bjs.11746; Kuhlen R et al., Dtsch Arztebl Int 2020; 117: 488-489). In der Kinder- und Jugendmedizin stehen die Fragen und Probleme des Schulunterrichts, der fehlenden sozialen Kontakte innerhalb der peer group und der häuslichen Gewalt im Vordergrund der Fragen zur Auswirkung der Pandemie auf die Gesundheit (Wade M et al., Psychiatry Res 2020; 290:113-143). Mögliche Auswirkungen auf die Umsetzung der Richtlinie des Gemeinsamen Bundesausschuss (G-BA) über die Früherkennung von Krankheiten bei Kinder (Vorsorge-Untersuchungen U1-U9) sind bislang nicht bekannt. Im Rahmen der SARS-CoV2 Kontaktbeschränkungen hatte der G-BA die Toleranzzeiten (Abrechnungsfristen) für die Vorsorge-Untersuchungen U6-U9 bis zum Ablauf von 3 Monaten nach Beendigung einer epidemischen Lage von nationaler Tragweite aufgehoben (BAnz AT 29.05.2020 B6).

Never too late? Quadruplets at the age of 65 years.

BACKGROUND: We discuss the challenges of multiple pregnancy at very advanced reproductive age. CASE PRESENTATION: We present the case of a quadruplet pregnancy at the maternal age of 65 following in-vitro fertilization (IVF) with donor eggs and sperm, involving cross-border reproductive care. All children born were at 25 weeks' gestation and survived; however, poor neurodevelopmental outcome remains a major concern in one child. CONCLUSIONS: The use of reproductive technology to achieve a multiple pregnancy at such an advanced post-menopausal age generated a debate on ethical, psychosocial and medical questions. We share this debate and highlight the need to reconsider international guidelines for women of advanced reproductive age.

[Prenatal Diagnostics and Postnatal Complications in a Case of Extremely Rare Tetra-Amelia]. / Pränatale Diagnostik und postnatale Komplikationen im Fall einer extrem seltenen Tetraamelie.

Tetra-amelia is extremely rare with an incidence of 2.4 per 10,000,000 births. It describes the absence of all 4 outer extremities and can be associated with other malformations. The boy presented here was diagnosed at 22 1/7 weeks of gestation by sonography in 2D and 3D mode. The parents decided to continue the pregnancy; vaginal birth occurred after external rotation at 38 1/7 weeks of pregnancy. Postnatally, surgical closure of a cleft of the soft palate was performed. External abnormalities manifested themselves increasingly in the area of the spine and the face. The anatomically limited psychomotor development of the child is supported by physiotherapy, occupational therapy, and speech therapy. Various aids enable the child to participate in activities appropriate to his age.

[... because We Should not Forget! Neonatal Organ Donation]. / ... denn wir dürfen sie nicht vergessen! Organspende in der Neonatologie.

Obwohl sich fast 40% aller Todesfälle im Kindes- und Jugendalter während der Neugeborenenperiode ereignen, kommt es in der Neonatologie nur selten zur Organspende. Wir berichten über ein Neugeborenes, bei dem nach perinataler Asphyxie der endgültige, nicht behebbare Ausfall der Gesamtfunktion des Großhirns, des Kleinhirns und des Hirnstamms ("Hirntod") gemäß Transplantationsgesetz diagnostiziert wurde. Das Herz wurde nach der sogenannten zweiten richtliniengemäßen "Hirntoddiagnostik" zur Organspende entnommen und erfolgreich transplantiert. Besondere juristische Herausforderungen ergaben sich aus dem Umstand der anonymen Geburt, den notwendigen Regelungen der Vormundschaft sowie der Zuordnung des Totenfürsorgerechts. Medizinisch standen die speziellen Regelungen der Diagnostik des irreversiblen Hirnfunktionsausfalls bei Neugeborenen und der optimale Erhalt der Organfunktion vor Entnahme im Vordergrund. Für die Pflegenden stellte sich der Ablauf grundlegend anders dar als bei einer Therapiezieländerung mit anschließender palliativen Versorgung in Anwesenheit der Eltern. Angesichts der großen emotionalen Herausforderungen erwiesen sich die Einbindung aller Beteiligten in die Entscheidungsabläufe und die Übernahme der besonderen Verantwortung als hilfreich.Although almost 40% of all deaths prior to 18 years of age occur within the neonatal period, organ donation is rare in neonatology. Herein we report about a newborn infant with perinatal asphyxia and permanent, irreversible loss of brain function (cerebrum, cerebellum and brain stem), managed according to the criteria and instructions defined by the German law of donor organ transplantation. After confirmation of irreversible loss of brain function, the heart was successfully transplanted. Specific legal challenges resulted from the instance of an anonymous birth, the guardianship required, and the specific regulations of welfare of the deceased individual. The most prominent medical challenges consisted in the specific regulatory purposes for the diagnosis of the irreversible loss of brain function in neonates and the optimal maintenance of organ functions prior to donation. From the nursing point of view, the proceeding differed entirely compared to redirection of care into palliation while parents are present. Involving all stakeholders in every step of decision making was regarded as emotionally helpful.

Pooling, room temperature, and extended storage time increase the release of adult-specific biologic response modifiers in platelet concentrates: a hidden transfusion risk for neonates?

BACKGROUND: Adult donor platelets (PLTs) are frequently transfused to prevent or stop bleeding in neonates with thrombocytopenia. There is evidence for PLT transfusion-related morbidity and mortality, leading to the hypothesis on immunomodulatory effects of transfusing adult PLTs into neonates. Candidate factors are biologic response modifiers (BRMs) that are expressed at higher rates in adult than in neonatal PLTs. This study investigated whether storage conditions or preparation methods impact on the release of those differentially expressed BRMs. STUDY DESIGN AND METHODS: Pooled PLT concentrates (PCs) and apheresis PCs (APCs) were stored under agitation for up to 7 days at room temperature (RT) or at 2 to 8°C. The BRMs CCL5/RANTES, TGFß1, TSP1, and DKK1 were measured in PCs' supernatant, lysate, and corresponding plasma. PLT function was assessed by light transmission aggregometry. RESULTS: Concerning the preparation method, higher concentrations of DKK1 were found in pooled PCs compared to APCs. In supernatants, the concentrations of CCL5, TGFß1, TSP1, and DKK1 significantly increased, both over standard (≤4 days) and over extended storage times (7 days). Each of the four BRMs showed an up to twofold increase in concentration after storage at RT compared to cold storage (CS). There was no difference in the aggregation capacity. CONCLUSION: This analysis shows that the release of adult-specific BRMs during storage is lowest in short- and CS APCs. Our study points to strategies for reducing the exposure of sick neonates to BRMs that can be specifically associated to PLT transfusion-related morbidity.

Screening for Third-Generation Cephalosporin-Resistant Bacteria Reduces the Incidence on Late-Onset Sepsis and Antibiotic use in Neonates.

BACKGROUND: The extensive use of antibiotics is reflected by an increasing prevalence of infections with multidrug-resistant bacteria, including third-generation cephalosporin-resistant bacteria (3GCRB). For neonatal intensive care units screening and enhanced barrier precautions are recommended to control the spread of multidrug-resistant Gram-negative bacteria, while evidence for efficacy of barrier precautions remains scarce in a non-outbreak setting. OBJECTIVE: To determine the impact of a screening program for maternal 3GCRB colonization and the effects of contact precautions and cohort nursing, concerning the risk of neonatal late-onset sepsis (LOS) and antibiotic use rates (AURs). STUDY DESIGN: In a retrospective matched-pair cohort study, data of neonates exposed to maternal 3GCRB colonization were compared with findings in non-exposed neonates. RESULTS: Of 3,144 neonates admitted, 184 neonates born to 3GCRB-positive mothers were eligible. Among them, 37 (20%) became 3GCRB positive during hospital stay. 3GCRB-exposed infants had a lower rate of LOS (6.5 vs. 14.1%, p=0.03) and lower AURs in that time period compared to controls (mean 0.009 vs. 0.025, p=0.006). When started within the first 72h after birth, days of therapy with meropenem were significantly lower in non-exposed vs. 3GCRB-exposed infants (mean 0.13 vs. 0.42; p=0.002). No invasive infections with 3GCRB occurred. CONCLUSIONS: Neonates of 3GCRB-positive mothers do not have an increased a priori risk for invasive 3GCRB infection and may benefit from enhanced contact precautions measures. HINTERGRUND: Der zunehmende Einsatz von Antibiotika führt zu einem Anstieg von Infektionen mit multiresistenten Erregern wie z. B. Drittgeneration Cephalosporin-resistenten Bakterien (3GCRB). Empfehlungen zu Screening- und Kohortierungsmaßnahmen auf neonatologischen Intensivstationen zielen auf die Prävention von horizontaler Transmission und invasiven Infektionen ab. Für Nicht-Ausbruchssituationen ist die Evidenz für Hygienemaßnahmen und Screeningprogrammen unzureichend. ZIEL: Evaluation eines Screening für mütterliche 3GCRB-Besiedlung mit nachfolgender Isolation bzw. Kohortenpflege des Neugeborenen (NG) unter Bezug auf das Risiko einer Late-Onset-Sepsis (LOS) und die Anzahl der Antibiotika-Tage (AUR). STUDIENDESIGN: In einer retrospektiven Fall-Kontroll-Kohortenstudie wurden Daten von NG mit maternaler 3GCRB-Besiedelung im Vergleich zu einer Kontrollgruppe mit unauffälligem Screening analysiert. ERGEBNISSE: In einer Kohorte von 3144 NG fanden sich 184 NG von 3GCRB-besiedelten Müttern. Bei 37 (20%) wurde im Verlauf eine Besiedelung mit 3GCRB nachgewiesen. In der Gruppe der 3GCRB-exponierten NG kam es seltener zu einer LOS (6,5 vs. 14,1%, p=0,03). Zwischen dem 4. Lebenstag und der Entlassung hatten 3GCRB-exponierte NG eine niedrigere AUR (Mittelwert 0,009 vs. 0,025, p=0,006) als die Kontrollgruppe. Die Behandlungstage mit Meropenem (Start in den ersten 3 Lebenstagen), war in der Kontrollgruppe signifikant geringer als in der 3GCRB-exponierten Gruppe (Mittelwert 0,13 vs. 0,43 Tage; p=0,002). In beiden Gruppen trat keine invasive Infektion mit 3GCRB auf. SCHLUSSFOLGERUNG: Neugeborene, deren Mütter 3GCRB besiedelt sind, haben kein erhöhtes a priori Risiko für eine invasive Infektion mit 3GCRB Erregern und profitieren wahrscheinlich von erweiterten Kohortierungs- und Isolationsmaßnahmen.

The Erythropoietin Promoter Variant rs1617640 Is Not Associated with Severe Retinopathy of Prematurity, Independent of Treatment with Erythropoietin.

In this case-control study, the erythropoietin (EPO) promoter variant s1617640, linked to high intravitreal EPO concentrations and increased risk of diabetic retinopathy, was not associated with severe retinopathy of prematurity. This finding was observed both in infants with and without recombinant EPO administration.

[New Challenges: Diagnosis of Brain Death in Newborn, Children and Adolescents]. / Neue Herausforderungen: Feststellung des irreversiblen Ausfalls der Hirnfunktion bei Neugeborenen, Kindern und Jugendlichen.

BACKGROUND: According to the current update of the German guideline on brain death (BD), participation of paediatricians is now mandatory for the examination of BD in patients younger than 14 years. The present analysis focuses on the previous practice and highlights the challenges that arise from the current update. METHODS: Retrospective evaluation of the patient registry of the German organ procurement organisation (north-eastern bureau) between January, 2001 and December, 2010 with specified paediatric age groups according to the 4th update of the German guideline on BD from the 1st of July 2015. RESULTS: 133 patients (0-17 years) received at least one BD examination. Secondary brain damage was most frequent within the first 6 months of life whereas traumatic and other causes of primary brain damage were predominantly observed thereafter. The number of patients who received BD examination by paediatricians or were treated on neonatal/paediatric intensive care units declined with increasing age. In more than two-third of all paediatric patients, no paediatrician was involved in BD diagnostics. DISCUSSION: After enforcement of the 4th update of the German guideline on BD, the participation of qualified paediatric physicians must be increased significantly compared to previous practice. Advancements in the specialist training of paediatric physicians, adjustments in patient-centered paediatric care and interdisciplinary diagnostic teams may be solutions to meet this demand.

Familial Gordon syndrome associated with a PIEZO2 mutation.

Gordon syndrome or distal arthrogryposis type 3 is a rare autosomal dominant disorder characterized by contractures of upper and lower limbs. It is distinguishable from other forms of distal arthrogryposis by cleft palate and short stature. Recently, Gordon syndrome has been associated to heterozygous mutations in the piezo-type mechanosensitive ion channel component 2 gene (PIEZO2). Different mutations of this gene also cause distal arthrogryposis type 5 and Marden-Walker syndrome. Dysfunction of this ion channel provides pleiotropic effects on joints, ocular muscles, and bone development. Here, we present a family with three affected individuals exhibiting multiple contractures (metacarpo-phalangeal and interphalangeal joints as well as elbow, shoulder, knee, and ankle joints), clubfeet, short stature, bifid uvula/cleft palate, and a distinct facial phenotype including ptosis. In addition, mild intellectual disability and delay in psychomotor development are obvious. The multigenerational phenotypic spectrum of Gordon syndrome is present in the 37-year-old father, his 4-year-old son and a male neonate showing typical signs of arthrogryposis in the prenatal ultrasound examination already seen at 13 week of gestation. In all affected family members, we identified the PIEZO2 mutation c.8057G>A (p.Arg2686His) by Sanger sequencing. Our analysis indicated that mild delay in psychomotor development and intellectual disability could be part of the phenotypic spectrum of Gordon syndrome. © 2016 Wiley Periodicals, Inc.

Fresh frozen plasma transfusion - a risk factor for pulmonary hemorrhage in extremely low birth weight infants?

AIM: To evaluate risk factors for pulmonary hemorrhage (PH) in extremely low birth weight infants (ELBW) taking into consideration coagulation screens, platelet counts, transfusion of fresh frozen plasma (FFP), and platelet concentrates prior to PH. PATIENTS AND METHODS: A retrospective case-control study consisting of 20 ELBW infants with PH and 40 matched controls. Coagulation screens, platelet counts at birth and at onset of PH, and transfusion frequencies prior to PH were compared to case-controls at birth and 24-96 h after birth. RESULTS: While the initial platelet counts, fibrinogen concentrations, and international normalized ratios were similar in PH infants and controls, the activated partial prothrombin time was prolonged (P=0.05). Compared to 28% of case controls (P<0.05), 55% of infants with later PH received FFP prior to PH. Platelet counts were significantly lower at onset of PH (median 81/nL; range: 37-236/nL) compared to controls (166/nL; 27-460/nL; P<0.005). Multivariate analysis indicated a lack of antenatal steroids, supplemental oxygen, and transfusion of FFP as independent risk factors for PH. CONCLUSION: Prolonged activated partial thromboplastin time (aPTT) might be associated with PH. PH does not primarily depend upon severe thrombocytopenia. A developmental mismatch in hemostasis by transfusion of adult donor plasma should be considered a risk factor for PH.

The rationale for third trimester testing of vertical HIV transmission in neonates with CMV infection.

We report on a late-preterm neonate with severe congenital cytomegalovirus (CMV) infection, refractory to antiviral therapy with ganciclovir. Subsequent immune diagnostics led to the finding of HIV infection at day 69, even though the mother tested negative for HIV in early pregnancy. Thus, in congenital CMV infection, HIV testing should be performed to elucidate maternal HIV seroconversion during late pregnancy. Our case strongly supports third trimester screening of HIV infection acquired during pregnancy, yet recommended only for women with traditional risk factors for HIV or living in an area of high HIV prevalence.

Transcription factor Yin-Yang 2 alters neuronal outgrowth in vitro.

The Yin-Yang 2 (YY2) protein is the most recently described member of the family of YY transcription factors. Despite its high structural and functional homology with the well-characterized YY1, less is known about its role in biological processes. In previous studies, we have found differential yy2 mRNA expression levels in various cell types of the murine brain. To investigate the functional implication of yy2 in neurons, we have examined the influence of altered cellular yy2 concentrations during neuronal differentiation. Our results indicate that both the up- and down-regulation of yy2 significantly impairs the outgrowth of the major neurite of primary hippocampal neurons and the numbers of neuronal processes in proximate extensions. Moreover, enhanced expression of wild-type yy2 results in increased cell death, whereas elevated expression levels of a yy2 DNA-binding mutant have no effect on cell viability. Therefore, stringent regulation of the cellular yy2 content might be needed to ensure proper neurite outgrowth and cell vitality.

Safety of Early High-Dose Recombinant Erythropoietin for Neuroprotection in Very Preterm Infants.

OBJECTIVE: To investigate the safety and short term outcome of high dose recombinant human erythropoietin (rhEpo) given shortly after birth and subsequently over the first 2 days for neuroprotection to very preterm infants. STUDY DESIGN: Randomized, double masked phase II trial. Preterm infants (gestational age 26 0/7-31 6/7 weeks) were given rhEpo (nt = 229; 3000 U/kg body weight) or NaCl 0.9% (nc = 214) intravenously at 3, 12-18, and 36-42 hours after birth. RESULTS: There were no relevant differences between the groups for short-term outcomes such as mortality, retinopathy of prematurity, intraventricular hemorrhage, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. At day 7-10, we found significantly higher hematocrit values, reticulocyte, and white blood cell counts, and a lower platelet count in the rhEpo group. CONCLUSIONS: Early high-dose rhEpo administration to very premature infants is safe and causes no excess in mortality or major adverse events. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00413946.