Meropenem vs standard of care for treatment of neonatal late onset sepsis (NeoMero1): A randomised controlled trial.

BACKGROUND: The early use of broad-spectrum antibiotics remains the cornerstone for the treatment of neonatal late onset sepsis (LOS). However, which antibiotics should be used is still debatable, as relevant studies were conducted more than 20 years ago, recruited in single centres or countries, evaluated antibiotics not in clinical use anymore and had variable inclusion/exclusion criteria and outcome measures. Moreover, antibiotic-resistant bacteria have become a major problem in many countries worldwide. We hypothesized that efficacy of meropenem as a broad-spectrum antibiotic is superior to standard of care regimens (SOC) in empiric treatment of LOS and aimed to compare meropenem to SOC in infants aged 44 weeks meeting the Goldstein criteria of sepsis, were randomized in a 1:1 ratio to receive meropenem or one of the two SOC regimens (ampicillin+gentamicin or cefotaxime+gentamicin) chosen by each site prior to the start of the study for 8-14 days. The primary outcome was treatment success (survival, no modification of allocated therapy, resolution/improvement of clinical and laboratory markers, no need of additional antibiotics and presumed/confirmed eradication of pathogens) at test-of-cure visit (TOC) in full analysis set. Stool samples were tested at baseline and Day 28 for meropenem-resistant Gram-negative organisms (CRGNO). The primary analysis was performed in all randomised patients and in patients with culture confirmed LOS. Proportions of participants with successful outcome were compared by using a logistic regression model adjusted for the stratification factors. From September 3, 2012 to November 30th 2014, total of 136 patients (instead of planned 275) in each arm were randomized; 140 (52%) were culture positive. Successful outcome at TOC was achieved in 44/136 (32%) in the meropenem arm vs. 31/135 (23%) in the SOC arm (p = 0.087). The respective numbers in patients with positive cultures were 17/63 (27%) vs. 10/77 (13%) (p = 0.022). The main reason of failure was modification of allocated therapy. Treatment emergent adverse events occurred in 72% and serious adverse events in 17% of patients, the Day 28 mortality was 6%. Cumulative acquisition of CRGNO by Day 28 occurred in 4% of patients in the meropenem and 12% in the SOC arm (p = 0.052). CONCLUSIONS: Within this study population, we found no evidence that meropenem was superior to SOC in terms of success at TOC, short term hearing disturbances, safety or mortality were similar in both treatment arms but the study was underpowered to detect the planned effect. Meropenem treatment did not select for colonization with CRGNOs. We suggest that meropenem as broad-spectrum antibiotic should be reserved for neonates who are more likely to have Gram-negative LOS, especially in NICUs where microorganisms producing extended spectrum- and AmpC type beta-lactamases are circulating

Neurodevelopmental outcome in extremely low birth weight infants at 2–3 years of age

Background and objectives: The aims of this study were to examine the relationship between neurological outcomes at 3-and 6-months corrected age with the neurodevelopmental outcome at 3 years of age; to identify the perinatal/neonatal risk factors for poor neurodevelopmental outcomes at 3 years of age. Materials and methods: In our single-centre longitudinal cohort study, of the 73 consecutive infants admitted to our Neonatal Intensive Care Unit (NICU), 49 infants (80%) received both Hammersmith Infant Neurological Examination (HINE) at 3-and 6-months corrected age and Bayley–III neurodevelopmental assessment at 2–3 years chronological age. At 3 months follow up, 8.2% had suboptimal scores (below 10th percentile) on the HINE. At 6 months follow up, 4.1% had suboptimal scores (below 10th percentile) on the HINE. The means(±SD) for Bayley-III cognitive, language, and motor subscales were (96.3 ± 9.8), (99.9 ± 11.9), (93.2 ± 9.9). Results: At 3 months corrected age, higher total HINE scores and subscores for function of cranial nerves, posture, tone, were associated with better cognitive scores while poorer scores for function of cranial nerves, posture, movements, tone, and total HINE score were associated with lower motor scores. Infants with a HINE subscore of function of cranial nerves in the suboptimal range have three times higher odds of having a motor delay. Infants with a HINE subscore of function of cranial nerves in the suboptimal range have more than two times higher odds of having a language delay. At 6 months corrected age, poorer scores for function of cranial nerves, movements, tone, reflexes, and total HINE score were associated with worse Bayley-III motor scores whilst infants who have a total HINE score and a subscore of reflexes in the suboptimal range have four and seven times, respectively, higher odds of having a motor delay. Conclusions: Early identification of infants at risk for adverse long-term outcomes is essential in introducing early intervention therapies for optimizing neurodevelopmental outcomes. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Ein Neugeborenes mit spät einsetzender Hypokalzämie aufgrund eines nicht erkannten mütterlichen Hyperparathyreoidismus und eine systematische Übersicht über ähnliche Fälle

Objective: Neonatal seizures are alarming manifestations of an underlying significant disorder demanding immediate attention and intervention. Hypocalcemia, although rare, must be considered in the differential diagnosis of neonatal seizures.Method: We present an unusual case of a 10-day-old infant with unexplained symptomatic hypocalcemia, experiencing multiple episodes of focal tonic-clonic seizures, born by an entirely asymptomatic mother. Moreover, we conducted a systematic search in PubMed and Scopus databases to present a clinical overview of all similar cases.Result: Maternal laboratory investigation revealed markedly increased calcium levels with concomitant high parathyroid hormone levels due to a parathyroid adenoma, undiagnosed during antenatal checkup.Conclusion: This is one of the few cases in the literature where neonatal symptomatology led to the diagnosis of undiagnosed maternal hyperparathyroidism. Early detection and appropriate management of neonatal hypocalcemia could eliminate serious maternal and fetal morbidity.Zielsetzung: Krampfanfälle bei Neugeborenen sind alarmierende Manifestationen einer zugrunde liegenden signifikanten Störung, die sofortige Aufmerksamkeit und Intervention erfordert. Obwohl Hypokalzämien selten sind, müssen sie bei der Differentialdiagnose von Krampfanfällen bei Neugeborenen berücksichtigt werden.Methode: Wir präsentieren einen ungewöhnlichen Fall eines 10 Tage alten Kindes mit ungeklärter symptomatischer Hypokalzämie, bei dem mehrere Episoden fokaler tonisch-klonischer Anfälle auftraten. Das Kind wurde von einer völlig asymptomatischen Mutter geboren. Darüber hinaus haben wir eine systematische Suche in den PubMed- und Scopus-Datenbanken durchgeführt, um einen klinischen Überblick über alle ähnlichen Fälle zu erhalten.Ergebnis: Laboruntersuchungen bei der Mutter ergaben einen deutlich erhöhten Kalziumspiegel bei gleichzeitig hohen Nebenschilddrüsenhormonspiegeln aufgrund eines Nebenschilddrüsenadenoms, das während der vorgeburtlichen Untersuchungen nicht diagnostiziert wurde.Schlussfolgerung: Dies ist einer der wenigen Fälle in der Literatur, in denen die Neugeborenen-Symptomatik zur Diagnose eines nicht diagnostizierten mütterlichen Hyperparathyreoidismus führte. Eine frühzeitige Erkennung und angemessene Behandlung der neonatalen Hypokalzämie könnte eine schwerwiegende Morbidität bei Mutter und Kind verhindern

Comparative safety and efficacy of paracetamol versus non-steroidal anti-inflammatory agents in neonates with patent ductus arteriosus: A systematic review and meta-analysis of randomized controlled trials

Aim: Ibuprofen and indomethacin are the preferred drug treatment for patent ductus arteriosus (PDA) in preterm neonates. The comparative safety and efficacy of paracetamol as an alternative has not yet been well established. The aim of our study was to define the comparative efficacy and safety of paracetamol versus ibuprofen and indomethacin for PDA. Methods: We performed a systematic literature search in PubMed, Scopus and Cochrane databases on randomized controlled trials comparing the efficacy and/or the safety of paracetamol versus ibuprofen and/or indomethacin and meta-analysed the available data. Results: There were 1718 neonates from 20 eligible studies. Paracetamol did not differ from ibuprofen or indomethacin regarding the primary (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.69–1.26, P-value: 0.650, when compared to ibuprofen, and OR: 0.78; 95% CI: 0.20–3.02, P-value: 0.716, when compared to indomethacin) and overall (OR: 1.17; 95% CI: 0.82–1.66, P-value: 0.394, when compared to ibuprofen, and OR: 1.12; 95% CI: 0.58–2.15, P-value: 0.733, when compared to indomethacin) PDA closure rates. Paracetamol resulted in significantly reduced risk of oliguria and a tendency towards less gastrointestinal bleeding. Conclusion: There was no significant difference between paracetamol and ibuprofen or indomethacin in the PDA closure rates. However, paracetamol caused fewer adverse effects. © 2022 British Pharmacological Society

Thromboelastometry in Neonates with Respiratory Distress Syndrome: A Pilot Study

Background: Although respiratory distress syndrome (RDS) constitutes a postnatal risk factor for bleeding and thromboembolic events in neonates, few studies have addressed this issue. We aimed to evaluate the hemostatic profile of neonates with RDS using rotational thromboelastometry (ROTEM). Methods: An observational study was conducted from November 2018 to November 2020 in the NICU of General Hospital of Nikaia “Aghios Panteleimon”. Preterm and term neonates with RDS hospitalized in the NICU were included and EXTEM (tissue factor-triggered extrinsic pathway), INTEM (ellagic acid activated intrinsic pathway), and FIBTEM (with platelet inhibitor cytochalasin D) assays were performed at the onset of the disease. Results: A hypocoagulable profile was noted in neonates with RDS compared to controls, expressed as significant prolongation of EXTEM CT (clotting time) and CFT (clot formation time), lower EXTEM A10 (amplitude at 10 min), MCF (maximum clot firmness), and LI60 (lysis index). Furthermore, prolongation of INTEM CFT and FIBTEM CT, and decreased INTEM and FIBTEM A10 and MCF were found in neonates with RDS. Multivariable logistic regression analysis showed that RDS is an independent factor for the recorded alterations in ROTEM variables. Conclusions: RDS is associated with a hypocoagulable profile and greater hyperfibrinolytic potential compared to healthy neonates

Thromboelastometry in Neonates with Respiratory Distress Syndrome: A Pilot Study.

BACKGROUND: Although respiratory distress syndrome (RDS) constitutes a postnatal risk factor for bleeding and thromboembolic events in neonates, few studies have addressed this issue. We aimed to evaluate the hemostatic profile of neonates with RDS using rotational thromboelastometry (ROTEM). METHODS: An observational study was conducted from November 2018 to November 2020 in the NICU of General Hospital of Nikaia "Aghios Panteleimon". Preterm and term neonates with RDS hospitalized in the NICU were included and EXTEM (tissue factor-triggered extrinsic pathway), INTEM (ellagic acid activated intrinsic pathway), and FIBTEM (with platelet inhibitor cytochalasin D) assays were performed at the onset of the disease. RESULTS: A hypocoagulable profile was noted in neonates with RDS compared to controls, expressed as significant prolongation of EXTEM CT (clotting time) and CFT (clot formation time), lower EXTEM A10 (amplitude at 10 min), MCF (maximum clot firmness), and LI60 (lysis index). Furthermore, prolongation of INTEM CFT and FIBTEM CT, and decreased INTEM and FIBTEM A10 and MCF were found in neonates with RDS. Multivariable logistic regression analysis showed that RDS is an independent factor for the recorded alterations in ROTEM variables. CONCLUSIONS: RDS is associated with a hypocoagulable profile and greater hyperfibrinolytic potential compared to healthy neonates

The use of thromboelastography (TEG) and rotational thromboelastometry (ROTEM) in neonates: a systematic review

“Developmental hemostasis” refers to the dynamic process of gradual hemostatic maturation. Conventional coagulation tests seem to fail to accurately depict the in vivo hemostasis, while viscoelastic tests, thromboelastography (TEG), and rotational thromboelastometry (ROTEM) appear very promising as they provide insight more rapidly and accurately into the hemostatic potential. We systematically reviewed the literature in PubMed to examine the use of TEG and ROTEM in neonates. Our search yielded 34 studies, of which 18 concerned healthy neonates and 16 sick neonates. These viscoelastic tests have shown accelerated initiation of coagulation, increased clot strength, and increased fibrinolysis in healthy neonates compared to children and adults. Cord blood leads to a hypercoagulable state as compared to whole blood when testing is performed with TEG. Pre-term neonates have a more hypocoagulable profile, but balanced hemostasis, related to term neonates, that evolves to a more procoagulant phenotype over the first month of life. Critically ill neonates exhibit a more hypocoagulable profile as compared to healthy neonates. TEG and ROTEM have shown predictive value for bleeding events in critically ill neonates and neonates undergoing cardiopulmonary bypass or therapeutic hypothermia. Conclusion: TEG and ROTEM need to become part of the standard coagulation assessment in clinical settings in which hemostatic abnormalities are involved, as they seem to provide more rapid and accurate information regarding the hemostatic profile of the neonates. Their predictive value for bleeding events in critically ill neonates could lead to a more targeted therapy optimizing utilization of blood products

Table_1_Maternal diabetes and the role of neonatal reticulocyte hemoglobin content as a biomarker of iron status in the perinatal period.docx

AimsWe aimed to evaluate the effects of maternal diabetes on neonatal iron status, measuring erythrocyte indices including hemoglobin, hematocrit, reticulocytes, mean corpuscular volume (MCV), percent (%) hypochromia, ferritin, and additionally mean reticulocyte hemoglobin content (MCHr) as an early marker of iron deficiency, and examine the association between neonatal MCHr, red cell indices, and ferritin.Materials and MethodsWe conducted a hospital-based prospective cohort study in a tertiary neonatal unit of a University Hospital from 2018 to 2020. We enrolled 126 maternal-infant pairs of mothers whose pregnancy was associated with diabetes and 74 maternal-infant pairs from uncomplicated pregnancies. Erythrocyte indices were analyzed within the first twelve hours after birth. Erythrocyte parameters were compared between infants of the diabetes and the non-diabetic group. We examined the correlation of the neonatal MCHr with perinatal characteristics, including gestation, birth weight, maternal body mass index, the erythrocytic indices, maternal diabetes, maternal obesity, prematurity, small-for-gestational-age status, maternal preeclampsia, and maternal anemia. Finally, we evaluated the discordance between neonatal MCHr and neonatal ferritin.ResultsInfants of the diabetes group had a significantly lower MCHr (32.6 pg vs. 34.2 pg, p=0.003) compared with infants of uncomplicated pregnancies. Neonatal MCHr was significantly correlated with maternal hypochromia (r=-0.237, p=0.004) and neonatal MCV (r=0.674, pConclusionsMCHr was significantly lower in infants of mothers whose pregnancy was associated with diabetes compared with infants of non-diabetic mothers and correlated with neonatal and maternal red cell indices of iron deficiency. Since there was significant discordance between neonatal MCHr and ferritin during the first postnatal day, it is possible that MCHr could be used as a screening test for iron deficiency, especially in infants.</p