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Aim: The aim of the present study was to determine immediate changes of global and regional lung function after exogenous surfactant administration in mechanically ventilated infants with respiratory distress syndrome (RDS) using electrical impedance tomography (EIT) measurements. Materials and Methods: A prospective study was conducted in a Neonatal Intensive Care Unit at a university hospital. Seventeen preterm infants (<12 hours old) suffering from RDS were included in this study. Interventions taken were lowpressure recruitment maneuver, surfactant administration and minimal adjustments in ventilator settings. Repeated EIT measurements (401 in total) were performed before and after (15 min - 30 min) surfactant administration. Global lung function changes were assessed with two markers, namely absolute resistivity (AbsR) and normalized impedance change (ΔZ); redistribution of regional lung ventilation was assessed as well. Airway pressure and arterial blood gases were recorded. Results: Surfactant administration resulted in a statistically significant increase of both the AbsR and ΔZ markers. Moreover, there was a ventilation shift towards dorsal - dependent lung areas with less asymmetry in the right-to-left air distribution. Conclusions: Surfactant administration in the recruited lung with RDS modifies regional ventilation, as assessed by EIT, contributing to a more homogeneous air distribution. Furthermore, significant changes in EIT markers reflect improvement of global lung function after surfactant administration. [ABSTRACT FROM AUTHOR]

Background: Attendance to neonatal follow-up programs presents a significant factor associated with positive long-term outcomes of high-risk infants. Strategies to maximize participation benefit not only future interventions' effectiveness but also healthcare systems and society. While a number of studies have focused on attrition or loss to follow-up, no studies have focused on the contributive risk factors to abstaining from neonatal follow-up programs specifically during the COVID-19 pandemic. This study aims to reveal the main factors linked to non-compliance in a neonatal follow-up program of a tertiary hospital., Methods: In this ambidirectional observational study, data from 1137 high-risk neonates who participated in a hospital follow-up program were collected (573 before and 564 after the COVID-19 pandemic). The study sample was grouped to three groups: G1 (N = 831), who maintained participation in the program; G2 (N = 196), who discontinued; and G3 (N = 110), who never visited the outpatient clinics. Data were obtained from the hospital's Systems Applications and Products (SAP) Software and a structured questionnaire, answered by parents of newborns either discontinuing (G2) or not attending (G3) the follow-up program through a telephone contact., Results: The most frequently reported reason for discontinuance before the pandemic onset was the parents' perception of no necessity to maintain participation (44.12%). During the COVID-19 pandemic, provider-related barriers to maintaining hospital access, inability to provide high-quality services (37.14%), and feelings of fear and insecurity (18.5%) emerged as factors for non-attendance. Citizenship and morbidity (respiratory distress syndrome, sepsis, necrotic enterocolitis, jaundice) acted as incentives to join the follow-up program during both study periods. Multiple regression analysis showed that multiple-gestation infants had higher odds of maintaining participation during the COVID-19 period (OR, 4.04; CI, 1.09-14.9)., Conclusions: Understanding the potential impact of COVID-19 and the transformative changes in neonatal follow-up clinics is crucial for applying compliance strategies. Removing barriers to maintain family participation can lead to increased attendance rates., Competing Interests: The authors declare no conflicts of interest.

Developmental hemostasis refers to age-related alterations related to the progressive maturation of the hemostatic system. Although the conventional coagulation tests, such as prothrombin time (PT) and activated partial thromboplastin time (aPTT), are indeed helpful in coagulation workup, they do not accurately delineate the hemostasis in vivo. The viscoelastic tests, namely thromboelastography (TEG) and rotational thromboelastometry (ROTEM), seem to reflect hemostasis more accurately since they measure various clot parameters without excluding the cellular coagulation components. TEG and ROTEM have shown redaction in blood product administration when used in therapeutic algorithms in older children and adults, but their use in neonates is limited. This review summarizes the current literature regarding using these tests in the neonatal population. Several studies tried to resolve the lack of neonatal reference values of the TEG/ROTEM parameters by publishing neonatal reference ranges for various gestational age groups. Moreover, few studies concerning therapeutic hypothermia, neonates undergoing surgery, and critically ill neonates have shown some predictive value of these tests regarding bleeding events. Even though their results seem promising, larger studies of higher quality are needed to clarify any discrepancies and point out whether these tests have significant predictive value. In conclusion, viscoelastic tests need to be increasingly part of the NICUs' clinical routine and should be used along with conventional coagulation tests in transfusion therapy.

Objectives: During pregnancy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection may intensify the gestational procoagulant state. Coronavirus disease 2019 (COVID-19) associated coagulopathy (CAC) constitutes an exacerbated immunothrombosis response. There is limited data regarding the coagulation profile of SARS-CoV2-infected pregnant women, especially those with CAC, and the effect on their offspring. This prospective study aimed to compare the hemostatic profile of those women and their neonates with healthy mother-neonate pairs., Methods: Conventional coagulation tests (CCTs) and rotational thromboelastometry (ROTEM) were employed to evaluate the hemostatic profiles. Neonates were assessed at birth and on the fourth day of life., Results: We enrolled 46 SARS-CoV2-infected pregnant women and 22 healthy controls who gave birth to 47 and 22 neonates, respectively. CAC was present in 10 participants. SARS-CoV2-infected pregnant women manifested slightly prolonged APTT and higher fibrinogen levels. Regarding ROTEM, we noted decreased FIBTEM CFT, with higher A10, A-angle, and MCF. The CAC group presented lower platelet count, increased fibrinogen levels, and higher FIBTEM A10 and MCF. PT was slightly prolonged at birth in neonates born to SARS-CoV2-infected mothers. During the fourth day of life, D-dimers were significantly increased. Concerning ROTEM, neonates born to SARS-CoV2-infected mothers showed lower FIBTEM CT at birth., Conclusions: SARS-CoV2-infected pregnant women present a hypercoagulable profile. Hypercoagulability with elevated fibrinolysis and lower platelet count is observed in participants with CAC. The coagulation profile of neonates born to SARS-CoV2 mothers seems unaffected. Elevated D-dimers on the fourth day may reflect a neonatal inflammatory response to maternal SARS-CoV2., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Pre-eclampsia (PE) is a placenta-mediated disease and remains a major cause of maternal and neonatal mortality and morbidity. As PE develops, normal pregnancy's hypercoagulable balance is disrupted, leading to platelet hyperactivation, excessive pathological hypercoagulability, and perturbed fibrinolysis. This narrative review aims to summarize the current knowledge regarding hemostasis in PE compared with healthy gestation and the potential effects of maternal PE on neonatal hemostasis. Finally, it aims to discuss hemostasis assessments for normal pregnancies and PE, emphasizing the role of viscoelastic tests, namely, thromboelastography (TEG) and thromboelastometry (ROTEM), for monitoring PE-associated hemostatic alterations. The use of TEG/ROTEM for assessing the hemostatic profile of PE women has been little considered, even though conventional coagulation tests (CCTs) have not helped to monitor hemostasis in this population. Compared with normal pregnancy, TEG/ROTEM in PE reveals an excessive hypercoagulability analogous with the severity of the disease, characterized by higher-stability fibrin clots. The TEG/ROTEM parameters can reflect PE severity and may be used for monitoring and as predictive markers for the disease.

Objective: This systematic review and meta-analysis (SRMA) aims to compare the efficacy of combining low molecular weight heparin (LMWH) and aspirin against aspirin alone in preventing preeclampsia (PE) and small for gestational age (SGA) neonates in women at moderate and high risks., Study Design: The included studies were nonrandomized and randomized clinical trials (RCTs) enrolling women at moderate and high risks for developing preeclampsia. PubMed/Medline, Cochrane Library, Embase, and Grey literature (including ClinicalTrials.gov) were searched., Results: Out of 4,762 records, 7 nonrandomized studies and 12 RCTs (enrolling 545 and 1,677 women, respectively) were selected. Although the studies were clinically heterogeneous, the conduction of quantitative analysis was feasible. Regarding RCTs, the odds of early-onset preeclampsia was reduced by 89% (pooled odds ratio [OR] = 0.11, 95% confidence interval [CI]: 0.01-0.93, p  = 0.04) in women with thrombophilia, the incidence of SGA neonates below the 5th percentile by 48% (pooled OR = 0.52, 95% CI: 0.28-0.96, p  = 0.04) in women with a history of preeclampsia and/or SGA neonates, and the incidence of SGA neonates below the 10th percentile by 31% (pooled OR = 0.69, 95% CI: 0.50-0.96, p  = 0.03) in the whole population., Conclusion: Concerning the whole studied population, combined anticoagulant therapy is not superior to aspirin alone. However, it may be more effective in preventing early-onset preeclampsia regarding women with thrombophilia, SGA neonates below the 5th percentile regarding women with a history of preeclampsia and/or SGA, and SGA neonates below the 10th percentile in moderate- or high-risk women. The above mixed but promising results need to be envisaged with caution due to the clinical heterogeneity of the included studies which is the main limitation of our research. Nevertheless, the strict and narrow inclusion search criteria, and the appropriate subgroup analysis are its main strengths. More RCTs with homogeneous populations and stricter inclusion criteria are needed to confirm these results., Key Points: · Combined therapy is not superior to aspirin alone.. · Combined therapy in women with thrombophilia may protect against early-onset preeclampsia.. · Combined therapy in moderate/high-risk women may protect against SGA <10th percentile neonates.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Neonatal sepsis is frequently accompanied by coagulopathy and thrombocytopenia attributed to the cross-link between inflammation and coagulation. However, sepsis-induced coagulopathy and platelet function in septic preterm neonates remain to be elucidated. In addition, there is no robust evidence for a causal relationship between thrombocytopenia and bleeding in preterm neonates with sepsis., Objective: This single-center prospective cohort study aimed to assess sepsis-induced coagulopathy and platelet function in preterm neonates during sepsis., Methods: We included 25 preterm neonates with Gram-positive sepsis born at gestational age 24 + 1 to 34 + 3 and studied in comparison to 30 healthy counterparts. Coagulation was assessed using conventional coagulation tests (CCTs) and rotational thromboelastometry (ROTEM). Platelet function was evaluated by flow cytometry. The study was conducted at 3-time points, at 1st, at 2nd to 3rd, and at 5th to 7th day of sepsis, respectively., Results: Compared with healthy controls, neonates with Gram-positive sepsis present in ROTEM a hypercoagulable state; a higher maximum clot firmness (MCF) and higher amplitudes of intrinsic rotational thromboelastometry (INTEM) (INTEM MCF: median, 71; P .004 and INTEM A10: median, 67; P .005, respectively), extrinsic rotational thromboelastometry (EXTEM) (EXTEM MCF: median, 70; P .02 and EXTEM A10: median, 67; P .02, respectively), and rotational thromboelastometry assay for fibrin formation (FIBTEM) (FIBTEM MCF: median, 25; P  < .001 and FIBTEM A10: median, 23; P .002, respectively). Conversely, CCTs exhibited hypocoagulation. Thrombocytopenia in preterm neonates with Gram-positive sepsis is not associated with an increased bleeding risk. In Gram-positive sepsis, platelets display increased glycoprotein (GP) surface receptors' expression (GPIb: median, 2.8; P .03, GPIIb: median, 3.1; P .004, and GPIIIa: median, 3.9; P .008, respectively) and reduced activation (P-selectin: median, 1; P  < .001). A higher expression of platelets GP and improved degranulation capacity were recorded in patients in higher gestational age groups of >32 weeks of gestation. Platelet GPIb expression is age-dependent in healthy neonates., Conclusion: Neonatal Gram-positive sepsis is characterized by a progressive hypercoagulation along with increased GP expression, reduced platelet activation, and thrombocytopenia without bleeding. Platelet GP expression and degranulation capacity are age-dependent among neonates with sepsis. Platelet GP expression is age-dependent among healthy counterparts., (© 2023 The Author(s).)

Objectives: Although the vaccination against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS Cov-2) is considered safe during pregnancy, vaccine hesitancy among pregnant women is high. The results of published observational studies addressing the issue of Covid-19 vaccination's efficacy and safety during pregnancy need to be summarized., Content: This systematic review compares the incidence of major maternal and neonatal outcomes between SARS Cov-2 vaccinated and unvaccinated pregnant women. The included studies enrolled pregnant women of any age and any trimester. Medline-Pubmed, Scopus, Cochrane Library, and grey literature were searched until the 28th of May 2022, and 2,947 studies were found., Summary: Seven observational cohort studies, enrolling 67,274 pregnant women, were selected. When comparing vaccinated and unvaccinated pregnant women, SARS Cov-2 vaccines were not associated with major maternal and neonatal adverse events. The rate of SARS Cov-2 infections among vaccinated pregnant women compared to unvaccinated is significantly reduced by 43%., Outlook: SARS Cov-2 vaccination in pregnant women is effective and safe. The results are promising, but caution is advised due to some limitations: only observational studies addressing this issue were found. Parallelly, the enrolled populations and the intervention (vaccination type and the number of doses) were not homogeneous., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Objectives: Developmental dysplasia of the hip (DDH) is a condition with variation among ethnicities and regions. We aimed to investigate the effect of a gestational week of birth on the sonographic acetabular hip angles of newborns., Methods: We prospectively scanned the hips of neonates born in a single, tertiary hospital during their first week of life, using the Graf sonographic method. Demographics, obstetric history of the mother, birth weight, parity, presentation, family history of developmental dysplasia of the hip (DDH), gender, mode of delivery, single/multiple birth, and gestational age were recorded. Acetabular α and β angles were measured, and hip type was determined according to Graf's classification. Patients were divided according to the gestational age of birth (<37 weeks, 37-38, 38-39, 39-40, >40 weeks)., Results: From May- October 2020, 342 babies (684 hips) were examined (52.9% males / 47.1% females). 76.7% were Caucasian-Greek, and 88.3% were term babies. There was a significant difference between the α-angles of the right and left hip in both genders. More females had Type II hips than males. Subgroup analysis did not reveal a significant difference in hip angles of term babies. There was no correlation between birth weight or gestational age and hip angles. Female gender and the existence of maternal thyroidopathy were positively correlated with Type II hips., Conclusion: Gestational birth age in term infants is unimportant regarding acetabular hip angles. Female gender and maternal thyroidopathy appeared to be related to hip type. Further investigation may be warranted to elucidate the effect of maternal thyroidopathy and hip development., Competing Interests: The author(s) do NOT have any potential conflicts of interest for this manuscript

Neonatal osteomyelitis (OM), although exceptionally rare, has been linked to detrimental sequel, as diagnosis in the early stages is challenging and any delay in treatment can lead to disturbance in skeletal growth. In pediatric OM the most commonly grown bacteria is Staphylococcus aureus followed by group A Streptococcus (GAS). Notwithstanding, sepsis-induced coagulopathy is a well-known entity in children and adults, still sepsis-associated thrombosis is sparsely observed. we present a case of a newborn with GAS associated OM and thrombosis. A term neonate on the 11th day of life was referred to our NICU due to right (R) lower limb edema, cyanosis and core temperature up to 39 °C. Late onset sepsis was suspected and started on vancomycin and amikacin. A colour Doppler scan showed thrombosis of the R common femoral vein. The neonate started on iv unfractionated heparin. Ampicillin was added given positive for GAS blood culture. An MRI on the 5th day of admission, showed evidence of thrombosis resolution. On the 14th day of admission, a bone Tc99 scan showed evidence of OM of R femur. Antibiotic treatment switched to amoxicillin per os. The management was restricted to anticoagulant therapy with low molecular weight heparin for 3 months and antibiotic therapy for 6 months without surgery intervention and the patient recovered and discharged at 42 days of age. Early diagnosis and treatment of neonatal osteomyelitis can prevent bone destruction. Sepsis-associated thrombosis is barely observed during osteomyelitis, yet it should be considered as an emerged case requiring prompt treatment.

Aims: We 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 Methods: We 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., Results: Infants 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, p<0.001). Neonatal MCHr was significantly associated with maternal diabetes [standardized coefficients 0.21, 95% confidence interval (CI) 0.05-0.58, p=0.003) and maternal preeclampsia (standardized coefficients 0.17, 95% CI 0.02-0.92, p=0.019), after adjusting for maternal anemia, maternal obesity, prematurity, and small-for-gestational-age status. Those results were consistent also when analyzing maternal-infant pairs with pre-existing diabetes, and maternal-infant pairs with gestational diabetes. There was significant discordance between neonatal MCHr and neonatal ferritin (p=0.001)., Conclusions: MCHr 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Babacheva, Rallis, Christou, Mitsiakos, Mikos, Dampala, Tsakalidis, Kioumi, Goulis and Soubasi.)

Introduction: The aim of our study was to establish reference ranges for neonatal coagulation and fibrinolysis parameters and to investigate their relationship with gestational age (GA) and birth weight (BW)., Methods: A single-centre prospective study was conducted in all healthy neonates born in our hospital during the study period, excluding those with maternal or neonatal disorders and diseases that affect haemostasis. The following parameters were measured: fibrinogen, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT) as well as factors II, V, VII, VIII, IX, X, XI and XII, von Willebrand (vWF), protein C, free protein S, antithrombin (AT), activated protein C resistance (APCr), tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1)., Results: Study population consisted of 327 neonates. Fibrinogen, AT III, proteins C and S, PAI-1, vWF and factors II, V, VIII, IX, XI and XII were positively correlated, while PT, aPPT, INR, APCr and tPA were negatively correlated with GA and BW. Proteins C and S, factors II, VIII, IX, XI and vWF, as well AT III and PAI-1 had a significant positive linear correlation with GA, while aPTT had a significant negative one. Fibrinogen, and factors V, VII and XII had a significant positive linear correlation with BW, while factor VIII, tPA, as well PT and INR had a significant negative one., Conclusion: Fibrinogen, AT III, proteins C and S, PAI-1, vWF and factors II, V, VIII, IX, XI and XII increase with GA and BW., (© 2022 John Wiley & Sons Ltd.)

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.)

Neonatal sepsis is considered critical for a significant increase in neonatal morbidity and mortality among hospitalized neonates. Neonatal sepsis, in most cases, coexists with coagulopathy, which can prove to be life-threatening. Complex molecular and cellular systems are involved in the cross-talk between inflammation and hemostasis during sepsis. Disturbances in the regulating systems of the vascular endothelium, and platelet-endothelial and platelet-neutrophil interactions play a pivotal role in both inflammation and coagulation. This complex process is poorly understood in neonates. In addition to the developmental maturation of hemostasis and the immune response in neonatal sepsis, a cellular model of hemostasis during sepsis should be taken into account. This review focused on the molecular and cellular mechanisms underlying inflammation and hemostasis during neonatal sepsis, taking the developmental immune response and developmental hemostasis into account in order to provide future diagnostic approaches to be applied in everyday clinical settings. Regarding the diagnostic modalities, we briefly provide the limitations of the currently used conventional coagulation assays, focusing on viscoelastic tests and platelet flow cytometry.

Background: Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme comprised extensive preclinical studies to inform a randomised controlled trial to assess optimised vancomycin dosing. We compared the efficacy of an optimised regimen to a standard regimen in infants with late onset sepsis that was known or suspected to be caused by Gram-positive microorganisms., Methods: NeoVanc was an open-label, multicentre, phase 2b, parallel-group, randomised, non-inferiority trial comparing the efficacy and toxicity of an optimised regimen of vancomycin to a standard regimen in infants aged 90 days or younger. Infants with at least three clinical or laboratory sepsis criteria or confirmed Gram-positive sepsis with at least one clinical or laboratory criterion were enrolled from 22 neonatal intensive care units in Greece, Italy, Estonia, Spain, and the UK. Infants were randomly assigned (1:1) to either the optimised regimen (25 mg/kg loading dose, followed by 15 mg/kg every 12 h or 8 h dependent on postmenstrual age, for 5 ± 1 days) or the standard regimen (no loading dose; 15 mg/kg every 24 h, 12 h, or 8 h dependent on postmenstrual age for 10 ± 2 days). Vancomycin was administered intravenously via 60 min infusion. Group allocation was not masked to local investigators or parents. The primary endpoint was success at the test of cure visit (10 ± 1 days after the end of actual vancomycin therapy) in the per-protocol population, where success was defined as the participant being alive at the test of cure visit, having a successful outcome at the end of actual vancomycin therapy, and not having a clinically or microbiologically significant relapse or new infection requiring antistaphylococcal antibiotics for more than 24 h within 10 days of the end of actual vancomycin therapy. The non-inferiority margin was -10%. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov (NCT02790996)., Findings: Between March 3, 2017, and July 29, 2019, 242 infants were randomly assigned to the standard regimen group (n=122) or the optimised regimen group (n=120). Primary outcome data in the per-protocol population were available for 90 infants in the optimised group and 92 in the standard group. 64 (71%) of 90 infants in the optimised group and 73 (79%) of 92 in the standard group had success at test of cure visit; non-inferiority was not confirmed (adjusted risk difference -7% [95% CI -15 to 2]). Incomplete resolution of clinical or laboratory signs after 5 ± 1 days of vancomycin therapy was the main factor contributing to clinical failure in the optimised group. Abnormal hearing test results were recorded in 25 (30%) of 84 infants in the optimised group and 12 (15%) of 79 in the standard group (adjusted risk ratio 1·96 [95% CI 1·07 to 3·59], p=0·030). There were six vancomycin-related adverse events in the optimised group (one serious adverse event) and four in the standard group (two serious adverse events). 11 infants in the intention-to-treat population died (six [6%] of 102 infants in the optimised group and five [5%] of 98 in the standard group)., Interpretation: In the largest neonatal vancomycin efficacy trial yet conducted, no clear clinical impact of a shorter duration of treatment with a loading dose was demonstrated. The use of the optimised regimen cannot be recommended because a potential hearing safety signal was identified; long-term follow-up is being done. These results emphasise the importance of robust clinical safety assessments of novel antibiotic dosing regimens in infants., Funding: EU Seventh Framework Programme for research, technological development and demonstration., Competing Interests: Declaration of interests PTH is a member of the National Institute for Health and Care Excellence neonatal infection guideline development group. LR is an employee of Therakind. DD obtained a PhD that was funded by Fondazione Penta; the capacity and remit of this PhD was independent and unrelated to involvement with NeoVanc. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Parvovirus B19 infection in pregnancy may have a poor outcome for the fetus. Ocular anomalies, brain damage with hydrocephalus and central nervous system (CNS) scarring, cleft lip and hypospadias, as well myocarditis and congenital heart disease have been reported. We present a case of a preterm female neonate born with ascites, hydrothorax and congenital diaphragmatic eventration (CDE), with a prenatal diagnosis of congenital diaphragmatic hernia (CDH). The neonate was born prematurely at 32 weeks gestation with caesarean section due to a previous caesarean delivery. She was immediately intubated in the delivery room, transferred in the Neonatal Intensive Care Unit (NICU) and supported with high frequency oscillatory ventilation (HFOV). The diagnosis of CDH was sonographically estimated from the 20th week of gestation and surgical correction was decided. During surgery CDE was diagnosed instead of CDH and despite postoperatively care the neonate developed disseminated intravascular coagulation and finally died in the 40th hour of life. Along with the identification of parvovirus B19 in the pleural fluid by PCR, the biopsy of the diaphragm revealed connective tissue, full of vasculature and absence muscle tissue. Although only cytomegalovirus, rubella, and toxoplasmosis were considered to be associated with CDE, parvovirus B19 might also be related to this congenital diaphragmatic malformation. In CDE, the function of the lungs can be compromised as a consequence of the compression applied by the abdominal organs. The neonatologists should include this condition in their differential diagnosis for a more direct and effective management.

"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. What is Known: • Conventional coagulation tests seem to fail to accurately depict the in vivo hemostasis. • TEG and ROTEM delineate more rapidly and accurately the hemostatic potential. What is New: • TEG and ROTEM have shown predictive value for bleeding events. • TEG and ROTEM may lead to a more targeted transfusion therapy optimizing utilization of blood products., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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.

G6PD deficiency is one of the most commonly inherited enzymopathies with a hallmark of an X-linked pattern. G6PD has more than 300 unique variants with different enzyme activity. The G6PD Mediterranean variant is prevalent in Greece and associated with asymptomatic patients who may experience haemolysis under specific circumstances. G6PD Harilaou is a new variant that was first described in Greece in an eight-year-old boy who suffered chronic haemolysis demanding multiple transfusions. We present a new case of the G6PD Harilaou variant in a Greek male neonate who suffered severe intrauterine haemolysis and passed away 39 hours after birth. To our knowledge, it is the second reported G6PD Harilaou case., (© 2021 Kleoniki I. Athanasiadou, MD et al. published by Sciendo.)

Objectives: Multiple pregnancies sustain the high pace of extreme prematurity. Little evidence is available about triplet gestation given the evolution in their management during the last decades . The aim of the study was to compare the neonatal outcomes of triplets with those of matched singletons in a cohort study., Methods: An observational retrospective cohort study of triplets and matched singletons born between 2004 and 2017 matched by gestational age was conducted. Additionally, the investigation performed in regard to data from the overall Greek population of interest. The primary outcome was mortality or severe neonatal morbidity based on pregnancy type., Results: A total of 237 triplets of 24-36 weeks' gestation and 482 matched singletons were included. No differences in the primary outcome between triplets and singletons were found. Rates of severe neonatal morbidities did not differ significantly between triplets and singletons. A threshold of 1000 gr for birthweight and 28 weeks' gestation for gestational age determined survival on triplets [OR: 0.08 (95% CI: 0.02-0.40, p=0.0020) and OR: 0.13 (95% CI: 0.03-0.57, p=0.0020) for gestational age and birthweight respectively]. In Greece stillbirths in triplets was 8 times higher than that of singletons (OR: 8.5, 95% CI: 6.9-10.5). From 3,375 triplets, 94 were stillborn, whereas in singletons, 4,659 out of 1,388,273. In our center 5 times more triplets than the expected average in Greece were delivered with no significant difference in stillbirths' rates., Conclusions: No significant differences were identified in mortality or major neonatal morbidities between triplets and matched singletons highlighting the significance of prematurity and birthweight for these outcomes., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

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.

Objective To examine cerebral oxygenation and perfusion in small for gestational age (SGA) compared with appropriate for gestational age (AGA) neonates during the first postnatal week, and to investigate any association with neurodevelopmental outcomes at 24-36 months of age. Methods A prospective matched case-control study was conducted evaluating cerebral oxygenation and perfusion, using near-infrared spectroscopy (NIRS), between SGA and AGA neonates, during the first postnatal week. A neurodevelopmental assessment with Bayley-III was performed at 24-36 months of age. Results Forty-eight SGA and 48 AGA neonates of similar gestation (32.8 ± 2.1 vs. 32.5 ± 1.9) were enrolled. On the first postnatal day, the cerebral oxygenation was equal between SGA and AGA neonates (71 ± 7% vs. 72 ± 8%); however, in the subgroup analysis, males had higher oxygenation compared to female SGA neonates (73 ± 7% vs. 69 ± 7%, P = 0.04). Cerebral perfusion was significantly higher in SGA neonates on the first postnatal day (1.4 ± 0.6 vs. 1.1 ± 0.5, P = 0.04), but this difference was diminished on subsequent measurements. There were no significant differences between the SGA and AGA infants regarding the composite cognitive, communication and motor index scores. The length of mechanical ventilation and late-onset sepsis were significant risk factors affecting the cognitive and communication composite index scores, respectively. Conclusion Cerebral oxygenation was equal between SGA and AGA neonates, while cerebral perfusion was transiently increased in SGA neonates during the first postnatal day. There was no significant association of cerebral oxygenation and perfusion with neurodevelopmental outcomes.