A Risk Score for Predicting the Incidence of Hemorrhage in Critically Ill Neonates: Development and Validation Study.

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.

Association of maternal Toll-like receptor-4 alleles with susceptibility to early-onset preeclampsia in central Greece.

INTRODUCTION: Altered maternal inflammatory responses may play a role in the development of hypertensive disorders of pregnancy like preeclampsia, its more severe early-onset form and intrauterine growth restriction. We evaluated the relation of common allelic variants of Toll-like receptor 4 (TLR4), known to impair the inflammatory response, with the susceptibility to early-onset preeclampsia in Central Greece. METHODS: We compared the occurrence of TLR4 (Asp299Gly and Thr399Ile) alleles in heterozygous (A/G, C/T) and homozygous (G/G, T/T) states in 84 women with a history of early-onset preeclampsia and 94 age matched controls with a history of only uneventful pregnancies, by direct sequencing. RESULTS: Heterozygous TLR4 allelic variants were more common in women with a history of early-onset preeclampsia than in controls (GA for Asp299Gly: 14.3% vs 6.4% (AA), p = 0.053 & CT for Thr399Ile: 16.7% vs. 6.4% (CC), p = 0.019) and a stronger association was obtained when homozygous allelic carriers were also included (GA/GG for Asp299Gly: 16.7% vs. 6.4% (AA), p = 0.03 & TC/TT for Thr399Ile: 19.0% vs. 6.4% (CC), p = 0.01). DISCUSSION: We recorded association between common TLR4 gene variants and early-onset preeclampsia. Our findings support the involvement of maternal innate immune system in severe hypertensive disorders of pregnancy and point to the potential value of maternal TLR4 polymorphisms as predictors-risk factors of susceptibility to early-onset preeclampsia in Central Greece.

Thromboelastometry for diagnosis of neonatal sepsis-associated coagulopathy: an observational study.

Our aim was to evaluate the potential role of standard extrinsically activated thromboelastometry (EXTEM) assay in the early detection of neonatal sepsis. We studied 91 hospitalized neonates categorized in two groups: group A included 35 neonates with confirmed sepsis, while group B included 56 neonates with suspected sepsis; 274 healthy neonates served as controls. Whenever sepsis was suspected, EXTEM assay was performed, Score for Neonatal Acute Physiology Perinatal Extension (SNAPPE) and Tοllner score were calculated, and clinical findings and laboratory results were recorded. Septic neonates had significantly prolonged clotting time (CT) and clot formation time (CFT), and reduced maximum clot firmness (MCF), compared to neonates with suspected sepsis (p values 0.001, 0.001, and 0.009, respectively) or healthy neonates (p values 0.001, 0.001, and 0.021, respectively). EXTEM parameters (CT, CFT, MCF) demonstrated a more intense hypocoagulable profile in septic neonates with hemorrhagic diathesis than those without (p values 0.021, 0.007, and 0.033, respectively). In septic neonates, CFT was correlated with platelet count, SNAPPE, Tollner score, and day of full enteral feeding (p values 0.01, 0.02, 0.05, and 0.03, respectively). CONCLUSIONS: A ROTEM hypocoagulable profile at admission seems promising for the early detection of sepsis in neonates while the degree of hypocoagulation may be associated with sepsis severity. What is Known: • The early phase of septicemia might be difficult to be recognized in neonates. In adult septic patients, the diagnostic and prognostic role of thromboelastometry (ROTEM) have been extensively investigated. • Limited data are available on the role of ROTEM as an indicator of early neonatal sepsis. What is New: • ROTEM measurements indicate an early appearance of hypocoagulability in neonatal sepsis, while the degree of hypocoagulation might be associated with severity of sepsis. • ROTEM could be a useful tool in the early detection of sepsis in neonates.

Reference ranges of thromboelastometry in healthy full-term and pre-term neonates.

BACKGROUND: Rotational thromboelastometry (ROTEM) is an attractive method for rapid evaluation of hemostasis in neonates. Currently, no reference values exist for ROTEM assays in full-term and pre-term neonates. Our aim was to establish reference ranges for standard extrinsically activated ROTEM assay (EXTEM) in arterial blood samples of healthy full-term and pre-term neonates. METHODS: In the present study, EXTEM assay was performed in 198 full-term (≥37 weeks' gestation) and 84 pre-term infants (<37 weeks' gestation) using peripheral arterial whole blood samples. RESULTS: Median values and reference ranges (2.5th and 97.5th percentiles) for the following main parameters of EXTEM assay were determined in full-term infants: clotting time (seconds), 41 (range, 25.9-78); clot formation time (seconds), 70 (range, 40-165.2); maximum clot firmness (mm), 66 (range, 41-84.1); lysis index at 60 min (LI60, %), 97 (range, 85-100). The only parameter with a statistically significant difference between full-term and pre-term neonates was LI60 (p=0.006). Furthermore, it was inversely correlated with gestational age (p=0.002) and birth weight (p=0.016) in pre-term neonates. CONCLUSIONS: In conclusion, an enhanced fibrinolytic activity in pre-term neonates was noted. For most EXTEM assay parameters, reference ranges obtained from arterial newborn blood samples were comparable with the respective values from studies using cord blood. Modified reagents, small size samples, timing of sampling, and different kind of samples might account for any discrepancies among similar studies. Reference values hereby provided can be used in future studies.

Bone metabolism compensates for the delayed growth in small for gestational age neonates.

The goal of the present study is to investigate the relationship between anthropometric and bone metabolism markers in a sample of neonates and their mothers. A sample of 20 SGA (small for the gestational age), AGA (appropriate for the gestational age) and LGA (large for the gestational age) term neonates and their 20 mothers was analyzed at birth and at exit. Elisa method was used to measure the OPG (Osteoprotegerin), RANK (Receptor activator of nuclear factor-kappaB), RANKL (Receptor activator of nuclear factor-kappaB Ligand), IGF-1 (Insulin-like growth factor 1), IGFBP3 (Insulin-like Growth Factor Binding Protein 3) and Leptin levels. Birth weight and length were positively correlated with RANKL, IGF-1 and IGFBP3 and negatively with the ratio OPG/RANKL. SGA neonates presented lower RANKL values and higher OPG/RANKL ratio while LGA neonates had higher RANK levels than AGA neonates. Positive association was shown between neonatal IGFBP3 and maternal IGF-1 values and between neonatal and maternal RANK values at birth and at exit. These results reveal a remarkable upregulation of OPG/RANKL ratio in SGA neonates, pointing out the role of bone turnover in compensating for the delayed neonatal growth.

Data analysis of the benefits of an electronic registry of information in a neonatal intensive care unit in Greece.

OBJECTIVES: This study assesses the results of implementation of a software program that allows for input of admission/discharge summary data (including cost) in a neonatal intensive care unit (NICU) in Greece, based on the establishment of a baseline statistical database for infants treated in a NICU and the statistical analysis of epidemiological and resource utilization data thus collected. METHODS: A software tool was designed, developed, and implemented between April 2004 and March 2005 in the NICU of the LITO private maternity hospital in Athens, Greece, to allow for the first time for step-by-step collection and management of summary treatment data. Data collected over this period were subsequently analyzed using defined indicators as a basis to extract results related to treatment options, treatment duration, and relative resource utilization. RESULTS AND DISCUSSION: Data for 499 babies were entered in the tool and processed. Information on medical costs (e.g., mean total cost +/- SD of treatment was euro310.44 +/- 249.17 and euro6704.27 +/- 4079.53 for babies weighing more than 2500 g and 1000-1500 g respectively), incidence of complications or disease (e.g., 4.3 percent and 14.3 percent of study babies weighing 1,000 to 1,500 g suffered from cerebral bleeding [grade I] and bronchopulmonary dysplasia, respectively, while overall 6.0 percent had microbial infections), and medical statistics (e.g., perinatal mortality was 6.8 percent) was obtained in a quick and robust manner. CONCLUSIONS: The software tool allowed for collection and analysis of data traditionally maintained in paper medical records in the NICU with greater ease and accuracy. Data codification and analysis led to significant findings at the epidemiological, medical resource utilization, and respective hospital cost levels that allowed comparisons with literature findings for the first time in Greece. The tool thus contributed to a clearer understanding of treatment practices in the NICU and set the baseline for the assessment of the impact of future interventions at the policy or hospital level.

Physicochemical stability of parenteral nutrition supplied as all-in-one for neonates.

BACKGROUND: Common clinical practice for the provision of parenteral nutrition of neonates is to administer the nutrients in separate solutions. The aim of this study was to introduce and examine an alternative way of parenteral feeding for neonates, providing all-in-one parenteral regimes. METHODS: Stability studies were carried out on 2 all-in-one admixtures. Stability assays consisted of the assessment of the admixture's (1) macroscopic aspect, (2) drop size measurement, (3) pH measurement, (4) peroxide value, and (5) alpha-tocopherol concentration. For the measurements, the admixtures were stored at 2 different temperatures, 4 degrees C (storage) and 25 degrees C (compounding), and then analyzed at a starting time, 24 hours, 48 hours, and 7 days after compounding. RESULTS: The 2 all-in-one parenteral admixtures for neonates were shown to be physically stable under analysis conditions, and there were no particles larger than 1 mum. The maximum loss of alpha-tocopherol was approximately 24%. In all-in-one admixtures, lipid peroxide occurred within 24 hours after the addition of the lipid emulsion. CONCLUSIONS: The addition of fat emulsion and fat-soluble vitamins did not alter the physical stability of parenteral admixtures for neonates. Moreover, the admixtures examined were relatively chemically stable for 24 hours, as far as vitamin E is concerned. Lipid peroxidation was the limiting factor for application stability of an all-in-one neonatal parenteral regimen.

Breast-feeding in Athens, Greece: factors associated with its initiation and duration.

OBJECTIVES: To determine the prevalence, examine the influence of hospital practices and investigate potential determinants of breast-feeding in Athens. PATIENTS AND METHODS: Three hundred twelve mothers provided information regarding feeding practices at certain maternity hospitals in Athens, at 40 days and 6 months postpartum. Multiple logistic regression analysis was performed to evaluate the association between the initiation and maintenance of breast-feeding and potential risk factors. RESULTS: Although almost 90% of newborn infants were given a breast milk substitute one or more times during the first 2 days at the maternity hospital, the exclusive breast-feeding percentage on the last day of hospital stay reached 85%. Breast-feeding and exclusive breast-feeding percentages dropped to 55% and 35%, respectively, at 40 days postpartum and to 16% and 12%, respectively, at 6 months postpartum. While in the hospital, 3% of mothers initiated breast-feeding within 1 hour of labor, only 34% were informed about the advantages of breast-feeding by health professionals and 42% were trained to breast-feed by the midwives. "Rooming-in" was not practiced in the private hospitals. The educational level was positively associated with the initiation of breast-feeding [odds ratio (OR): 1.36, confidence interval (CI): 1.02-1.81], the mother's body mass index was negatively associated with the maintenance of breast-feeding for 40 days (OR: 0.56, CI: 0.32-0.98) and 6 months (OR: 0.28, CI: 0.06-1.26) and a caesarean section was negatively associated with the initiation (OR: 0.24, CI: 0.11-0.49) and maintenance of breast-feeding (OR: 0.42, CI: 0.20-0.89). CONCLUSIONS: Breast-feeding is not appropriately supported in certain maternity hospitals in Athens, and this is probably the cause of observed low breast-feeding prevalence.

Gastric emptying in very-low-birth-weight infants treated with nasal continuous positive airway pressure.

OBJECTIVE: Nasal continuous positive airway pressure (NCPAP) is frequently used for prolonged periods in very low birth weight infants. We asked if NCPAP affects gastric emptying. STUDY DESIGN: Preterm newborn infants (n = 16) with a mean body weight of 935 g (SD, 155) and a mean gestational age of 27.7 weeks (SD, 1.9) were treated with NCPAP and fed by orogastric tube. A comparison group of 20 newborn infants with a mean body weight of 1090 grams (SD, 130) and a mean gestational age of 28.2 weeks (SD, 1.2) were not receiving NCPAP. All newborn infants received a milk formula containing 81 kcal/dL given in similar quantities. The antral cross-sectional area was measured by means of an ultrasound technique. RESULTS: Mean half-time of antral cross-sectional area was 28 minutes (SD, 12) in the NCPAP group and 40 minutes (SD, 17) in the comparison group ( P < .05). There were no differences in gastrointestinal complications between the two groups. CONCLUSIONS: The gastric emptying time was shorter for newborn infants treated with NCPAP.