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The aim of the study was to develop and validate a prediction model for hemorrhage in critically ill neonates which combines rotational thromboelastometry (ROTEM) parameters and clinical variables. This cohort study included 332 consecutive full-term and preterm critically ill neonates. We performed ROTEM and used the neonatal bleeding assessment tool (NeoBAT) to record bleeding events. We fitted double selection least absolute shrinkage and selection operator logit regression to build our prediction model. Bleeding within 24 hours of the ROTEM testing was the outcome variable, while patient characteristics, biochemical, hematological, and thromboelastometry parameters were the candidate predictors of bleeding. We used both cross-validation and bootstrap as internal validation techniques. Then, we built a prognostic index of bleeding by converting the coefficients from the final multivariable model of relevant prognostic variables into a risk score. A receiver operating characteristic analysis was used to calculate the area under curve (AUC) of our prediction index. EXTEM A10 and LI60, platelet counts, and creatinine levels were identified as the most robust predictors of bleeding and included them into a Neonatal Bleeding Risk (NeoBRis) index. The NeoBRis index demonstrated excellent model performance with an AUC of 0.908 (95% confidence interval [CI]: 0.870–0.946). Calibration plot displayed optimal calibration and discrimination of the index, while bootstrap resampling ensured internal validity by showing an AUC of 0.907 (95% CI: 0.868–0.947). We developed and internally validated an easy-to-apply prediction model of hemorrhage in critically ill neonates. After external validation, this model will enable clinicians to quantify the 24-hour bleeding risk.

Hypofibrinolysis has been demonstrated in several studies in adult sepsis. Although fibrinolysis is an important and integral part of the hemostatic system, few data are available regarding its role in neonatal sepsis. Our purpose was to define fibrinolytic profiles across neonatal sepsis spectrum using rotational thromboelastometry (ROTEM).This study was performed in a Greek tertiary General Hospital during an 18 month-period and included 44 neonates with confirmed sepsis and 22 with suspected sepsis; 110 healthy neonates served as controls. Whenever sepsis was suspected, EXTEM and APTEM assays were performed, clinical findings and laboratory data were recorded.Although most EXTEM parameters were significantly different among the 3 groups, Maximal Lysis (ML) and Lysis Index at 60 min (LI60) levels were similar (p = 0.11 and p = 0.20, respectively). Hyperfibrinolysis, as defined by ROTEM parameters, did not significantly differ among the study populations (p = 0.41). On the contrary, fibrinolysis shutdown, defined as an EXTEM LI60 ≥98%, was more common in septic neonates than in healthy (p 0.001) and neonates with suspected sepsis (p = 0.042). A weak to moderate correlation of LI60 and ML with mortality (Spearman rho = 0.43 and - 0.40, p = 0.005 and 0.007, respectively) and SNAPE score (Spearman rho = 0.35 and - 0.33, p = 0.02 and 0.03, respectively) was noticed in sepsis group.ROTEM, based on fibrinolytic parameters, showed a more frequent fibrinolysis shutdown in neonatal sepsis, but it could neither effectively discriminate septic neonates, nor predict their clinical outcome. The considerable overlap among numerical ROTEM values probably compromises their diagnostic clinical utility in neonatal sepsis.

Perinatal hypoxia is associated with an increased risk of coagulation disorders by enhancing the consumption of platelets and some clotting factors due to the associated severe hypoxemia, acidemia, and compromised oxygen and blood supply to the neonatal liver and bone marrow. Thromboelastometry (TEM), which estimates the dynamics of blood coagulation, may represent an attractive tool for studying the coagulation status of these neonates. We aimed at assessing the hemostatic profile of neonates with perinatal hypoxia using the standard extrinsically activated TEM (ex-TEM) assay. In total, 164 hospitalized neonates with perinatal asphyxia and/or fetal distress comprised the study subjects, and 273 healthy neonates served as controls. Ex-TEM assay was performed, SNAPPE (Score for Neonatal Acute Physiology Perinatal Extension) was calculated, and clinical findings and laboratory results were recorded in all study subjects. Hypoxic neonates expressed a prolonged clotting time (CT) and clot formation time (CFT) and reduced amplitude at 10 minutes (A10), α-angle, and maximum clot firmness compared with healthy neonates. Furthermore, asphyxiated neonates had a significantly prolonged CT and CFT and reduced A10 and α-angle compared with neonates with fetal distress. Hypoxic neonates demonstrate a hypocoagulable ex-TEM profile relative to healthy neonates, indicating a potential role of TEM in the early detection of coagulation derangement in perinatal hypoxia.

The aim of the present study was to assess the coagulation profile in neonatal critical illness using rotational thromboelastometry (ROTEM), and to investigate its association with disease severity and its potential prognostic role in this clinical setting. Over a period of 67 months (July 2014–February 2020) 423 critically ill neonates with confirmed or suspected sepsis, perinatal hypoxia, or respiratory distress syndrome, hospitalized in our neonatal intensive care unit were included in the study. Demographic, clinical, and laboratory data were recorded on admission day and arterial blood was analyzed on ROTEM analyzer using the standard extrinsically activated rotational thromboelastometry assay (EXTEM). Neonatal illness severity scores (Modified NEOMOD [Neonatal Multiple Organ Dysfunction] and SNAPPE [Score for Neonatal Acute Physiology with Perinatal Extension]) were calculated at the same time as ROTEM analysis. Mortality during in-hospital stay was the main outcome measure. Multivariable analyses showed that a 10 mm decrease in EXTEM clot amplitude recorded at 10 minutes (A10) is significantly associated with a higher mortality (odds ratio [OR] = 1.69, 95% confidence interval [CI]: 1.33–2.08). Higher modified NEOMOD (OR = 1.36, 95% CI: 1.26–1.47) and higher SNAPPE scores (OR = 1.06, 95% CI: 1.04–1.08) were also associated with increased mortality. The CT and A10 variables demonstrated the best prognostic performance among the EXTEM parameters for mortality (area under the curve [AUC] = 0.78; 95% CI: 0.69–0.86 and AUC = 0.76; 95% CI: 0.66–0.85, respectively), showing an optimal cut-off CT ≥63 seconds and A10 ≤37 mm. Using optimal cut-off values of the EXTEM parameters for prediction of mortality, neonates with CT ≥63 seconds were 7.4 times more likely to die (OR = 7.40, 95% CI: 3.50–15.65), while neonates with A10 ≤37 mm were 5.8 times more likely to die (OR = 5.88, 95% CI: 2.94–12.50). An EXTEM hypocoagulable profile on disease onset was shown to be an independent risk factor for in-hospital mortality in neonatal critical illness.

Backround The impact of the consistent implementation of “aggressive” nutrition by means of intensive early neonatal nutritional support up to 40–44 weeks postmenstrual age and the use of nasal continuous positive airway pressure (nCPAP) within the first hour of life on the respiratory function of very premature neonates (VPN) at school age is unclear. Method Respiratory function was evaluated in 108 VPN and 70 term controls. Growth, frequency of lower respiratory tract infections, re-hospitalization, and spirometry were recorded up to 8–10 years of age. Comparison was carried out between the two study groups. Results There was no significant difference in forced expiratory volume in 1 s and forced vital capacity at 8 years of age, and also in lower respiratory tract infections and re-hospitalization due to them, up to 8 years of age between preterm and term neonates. No significant difference was found in spirometry measurements neither between premature neonates with and without BPD nor between the two subgroups of preterms and term neonates. Conclusion “Aggressive” nutrition, persistent nCPAP use, and their impact on early postnatal growth probably positively affect the respiratory function of our study population. These very encouraging results need to be confirmed by larger studies.

Scarce data exists about the hemostatic status of small for gestational age (SGA) neonates. We aimed at evaluating the hemostatic profile of SGA neonates, using thromboelastometry (TEM). This is an observational study performed in a Greek tertiary General Hospital during an 18-month period. Ninety-three neonates were included in the study: 48 appropriate for gestational age weight (AGA) neonates and 45 SGA neonates Extrinsically activated TEM (ex-TEM) parameters, such as clotting time, clot formation time, amplitude recorded at 5 and 10 min, a angle, maximum clot firmness, lysis index at 60 min, and also platelet count, were used for the evaluation of the hemostatic profile in all neonates. No statistically significant differences were noticed regarding all ex-TEM parameters between AGA and SGA neonates, while no event of hemorrhage or thrombosis was noticed in the study population.Conclusions: The coagulation system of SGA neonates seems to be fully functional, with no evident tendency toward coagulopathy or thrombosis, when compared with AGA neonates. TEM seems to provide a promising and valid assessment of coagulation and fibrinolysis systems and may be used as a valuable biomarker, in the future. Further studies, with large samples, are necessary to confirm our results. What is Known: • SGA neonates may present coagulation disorders mainly due to hepatic dysfunction, polycythemia, and thrombocytopenia owing to long-term intrauterine hypoxia. • In the literature, despite the statistically significant differences in laboratory results between SGA and AGA neonates, no clinical manifestations of significantly altered hemostasis were recorded. Data of TEM interpretation of hemostasis in SGA neonates are not available. What is New: • TEM seems to interpret coagulation mechanism of preterm and full-term SGA neonates and confirm previous relevant literature findings regarding hemostasis in these neonates.

Introduction: The effects of “aggressive” neonatal feeding policies of very preterm neonates (VPN) and the risk of metabolic syndrome later in life remain questionable. We aimed to evaluate the effect of our “aggressive” nutrition policies of VPN during hospitalisation on body mass index (BMI) at ages 2 and 8 years. Materials and Methods: Eighty four VPN, who received “aggressive” nutrition during hospitalisation in an effort to minimise postnatal growth restriction (PGR) (group A), and 62 term neonates, as controls (group B), were enrolled in the study. Group A was further divided in four subgroups depending on the type (A1: fortified expressed breast milk and preterm formula, A2: exclusively preterm formula) and quantity of milk received (A3: maximum feeds 180–210 mL/kg/day, A4: maximum feeds 210 and up to 260 mL/kg/day). BMI was calculated at ages 2 and 8 years and plotted on the centile charts. Results: There was no significant difference in BMI between groups A and B at 2 and 8 years, respectively, in both absolute BMI values and their centile chart distribution. There was no significant difference in BMI at 2 and 8 years either between subgroups A1 and A2 or between subgroups A3 and A4. Conclusions: “Aggressive” and individualised feeding policy for VPN did not affect the BMI and obesity rates at ages of 2 and 8 years in our study population. The type and quantity of milk feeds had no impact on their BMI at school age. Further larger studies are needed to confirm our results.

"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.

Background: Caffeine has been commonly used for prevention and treatment of apnea-related symptoms in premature infants. However, its side effects have not been thoroughly studied. We investigated whether caffeine affects gastric motility in very-preterm (VP) neonates. Methods: The study is a randomized crossover clinical trial. Twenty-two neonates with mean birth weight (BW) (standard deviation&mdash, SD) 1077 (229) g and mean gestational age (GA) (SD) 28.6 (2.1) weeks were recruited. Each neonate had its gastric emptying time checked twice with ultrasound assessment of changes in antral cross sectional area (ACSA). All neonates were sequentially allocated to the caffeine group (A) and the control group (B). Complications from the gastrointestinal tract were documented throughout the study. Results: Statistically significant difference was found with regards to the gastric emptying time [median, (range)] between caffeine and control group (p = 0.040). Additionally, in the neonates with BW 1000&ndash, 1500 g and GA &ge, 28 weeks, the gastric emptying time (minutes) was significantly longer during caffeine treatment [44.5 (36&ndash, 68.2)] and [40 (34.5&ndash, 66.5)] respectively, as compared to the gastric emptying time during no caffeine treatment [27 (24.2&ndash, 30)] (p = 0.002) and [27 (24.5&ndash, 30)] (p = 0.001). The incidence of gastrointestinal (GI) complications was significantly greater in neonates receiving caffeine [6 (27.%)] as compared with those without caffeine treatment [1 (4.6%)] (p = 0.039). Conclusions: During caffeine treatment, a significantly delayed gastric emptying time was noted in all study neonates, especially in these with BW 1000&ndash, 1500 g and those with GA &ge, 28 weeks. Further larger studies are necessary in order to confirm this interesting finding.

Hemostasis is a dynamic age-related process, which gradually evolves from fetal life throughout childhood until adulthood. Although at birth there is a hemostatic deficit of most coagulation factors, studies have shown that this “hemostatic immaturity” is functionally counterbalanced in healthy term or preterm newborns. This delicate hemostatic balance is, however, deranged in sick neonates, resulting in an enhanced risk of hemorrhage and/or thrombosis. In critically ill neonates, conventional coagulation tests do not seem to provide reliable information or indications regarding the functional status of platelets or fibrinolysis. In contrast, viscoelastic tests, namely thromboelastography/thromboelastometry (TEG/TEM) hold promise for rapid assessment of the whole hemostatic potential, allowing immediate intervention should this be required. However, neonatal data are limited due to lack of reference values, especially in premature neonates. In this narrative review, we provide some insights around current knowledge regarding TEG/TEM applications in healthy and sick newborns. Overall, the use of viscoelastic tests in diagnosis and management of coagulation disorders in neonates is definitely worth further exploration. Consideration should be made to include these tests in the routine laboratory investigation of neonates and specific transfusion algorithms should also be developed in order to avoid treatment pitfalls.

We present a case of a term male neonate born with congenital diaphragmatic hernia (CDH), double-outlet right ventricle (DORV) and a “picture of genetic syndrome”, antenatally diagnosed, without any confirmation of a particular syndrome as no amnioparacentesis was performed. The postnatal chromosomal analysis revealed trisomy 18.