Paraskevi Karagianni

Early versus delayed minimal enteral feeding and risk for necrotizing enterocolitis in preterm growth-restricted infants with abnormal antenatal Doppler results.

We studied the effect of early (< or = 5 days) versus delayed (> or = 6 days) initiation of minimal enteral feeding (MEF) on the incidence of necrotizing enterocolitis (NEC) and feeding intolerance in preterm infants with intrauterine growth restriction (IUGR) and abnormal antenatal Doppler results. We performed a randomized, nonblinded pilot trial of infants receiving early or delayed MEF in addition to parenteral feeding within 48 hours of life. Demographic data, maternal preeclampsia, antenatal steroid exposure, Doppler studies, as well as cases of NEC and feeding intolerance were all recorded. Of the 84 infants enrolled, 81 completed the study: 40 received early (median age: 2 days, range: 1 to 5 days) and 41 delayed (median age: 7 days, range: 6 to 14 days) MEF. The incidence of NEC and feeding intolerance was not significantly different between groups (p = 0.353 and p = 0.533, respectively). Birth weight was an independent risk factor for NEC in both groups. Early MEF of preterm infants with IUGR and abnormal antenatal Doppler results may not have a significant effect on the incidence of NEC or feeding intolerance. Furthermore, birth weight seems to be an independent risk factor for the development of NEC, irrespectively of the timing of MEF introduction.

Loss of FEV1 in cystic fibrosis: correlation with HRCT features

Abstract. The purpose of this study was to determine which high-resolution computed tomography (HRCT) features in patients with cystic fibrosis are most strongly associated with functional impairment as expressed by forced expiratory volume in one second (FEV1). Forty-seven patients with cystic fibrosis underwent chest HRCT and had pulmonary function tests. The HRCT examinations were evaluated for 11 features scored using a modification of Bhalla system and FEV1 was recorded as percentage of the predicted value. Univariate and multivariate correlations between HRCT scores and FEV1 were performed. The most common HRCT feature was bronchiectasis (98%) followed by atelectasis–consolidation (81%), bronchial wall thickening (77%), tree-in-bud sign (74%), mucous plugging (72%) and mosaic perfusion pattern (47%). On univariate analysis the following features correlated strongly with FEV1: bronchial wall thickening (p<0.0000001), tree-in-bud sign (p<0.0000001), mucous plugging (p<0.0000001), atelectasis–consolidation (p<0.0000001), thickening of interlobular septa (p<0.0002), severity (p<0.0002) and extent of bronchiectasis (p<0.0002). On multivariate analysis bronchial wall thickening and atelectasis–consolidation were the strongest independent determinants of the FEV1. We found a regression equation between FEV1 and the two HRCT features: FEV1=constant variable+a multiplied by bronchial wall thickening+b multiplied by atelectasis–consolidation (a and b=regression coefficients, R2=0.48). The major morphological determinants of functional abnormality in cystic fibrosis, as expressed by the loss of FEV1, are bronchial wall thickening and atelectasis–consolidation.

Is the use of rFVIIa safe and effective in bleeding neonates? A retrospective series of 8 cases.

Background Recombinant activated factor VII (rFVIIa), originally developed for the treatment of life-threatening bleeding in hemophilic patients with inhibitors to factors VIII or IX, has been increasingly used to control hemorrhage unresponsive to conventional treatment, in the absence of a defined coagulopathy or thrombocytopathy. To date, clinical experience of rFVIIa administration in neonates, especially preterms, is rather limited, because of the lack of controlled studies and based solely on some published case reports and 1 prospective pilot study. The objective of this study was to retrospectively evaluate the clinical outcome of newborns treated with recombinant activated factor VII for intractable bleeding or severe coagulation disturbances, resistant to conventional hemostatic therapy. Methods The medical records of 8 neonates treated with rFVIIa (100  μg/kg) were retrospectively reviewed for the course of hemorrhage and the hemostatic interventions performed before and up to 24 hours after the administration rFVIIa. Coagulation parameters of 3 different time-points were assessed and compared: before administration of any blood product (time-point 1), before administration of the first dose of rFVIIa (time-point 2), and 4 hours after the administration of the last dose of rFVIIa (time-point 3). The safety and tolerability profile of rFVIIa in bleeding neonates was also evaluated. Results Six preterm and 2 term patients were included in the study. Seven patients presented with refractory bleeding and 1 was diagnosed with severe coagulopathy unresponsive to the conventional treatment. Prompt hemostasis was achieved in half of the patients with their coagulation profile being restored within 4 hours after the administration of the first dose of rFVIIa. Improvement in prothrombin time, activated partial thromboplastin time, and fibrinogen after rFVIIa administration was statistically significant, as compared with that observed after conventional treatment. No major safety issues were observed during the study. All 8 patients survived and had their hemorrhage or coagulopathy controlled within 4 hours after transfusion of the last dose of rFVIIa. Conclusions In this study, the hemostatic agent rFVIIa was well-tolerated and behaved in a safe and efficacious manner in all infants treated for life-threatening bleeding and coagulation disorders. Future prospective controlled trials are needed to determine the efficacy, safety, tolerability, and possibly the optimal dose and timing of rFVIIa administration.

Haemostatic profile of full-term, healthy, small for gestational age neonates

BACKGROUND Small for Gestational Age (SGA) neonates often appear with haemostatic alterations, principally due to hepatic dysfunction that results from chronic intrauterine hypoxia. Polycythaemia and thrombocytopenia are common findings in this neonatal population. STUDY DESIGN We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born full term [gestational age (G.A.) >37 weeks]. Study population consisted of 188 healthy newborns, 90 of whom were SGA (62 females and 28 males), while the rest were the control group (44 females and 54 males). Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, vWillebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test was used to compare the differences between the values of haemostatic parameters. RESULTS Statistical analysis revealed a significant prolongation in PT, INR, elevated levels of tPA (p<0.015, 0.01 and 0.002 respectively) and a decrease in the values of XII and free protein S (p<0.045 and 0.007 respectively) in SGA full term neonates. The two groups had similar demographic characteristics (except birth weight), without significant differences in the values of other haemostatic parameters. CONCLUSIONS Despite of statistically significant differences in PT, INR, values of tPA, XII and free protein S, levels of haemostatic factors range within laboratory references for healthy full term newborns. These findings were not accompanied with clinical manifestations of altered haemostasis.

Neuromotor Outcomes in Infants With Bronchopulmonary Dysplasia

We examine the neuromotor outcomes of preterm infants with bronchopulmonary dysplasia. Two hundred and nineteen infants (gestational age, ≤ 32 weeks; birth weight, ≤ 1500 g) were studied. Neuromotor development was assessed using the Hammersmith Infant Neurological Examination. All potential risk factors associated with neuromotor scores (P < 0.015) were included in the generalized linear model (multiple linear regression) to determine if bronchopulmonary dysplasia had an independent relationship with neuromotor scores. Infants with severe bronchopulmonary dysplasia had lower global scores at ages 6 and 12 months. After adjustment for confounding factors, scores of infants with severe bronchopulmonary dysplasia were reduced by 13.2 units, whereas scores for those with periventricular leukomalacia were reduced by 11.1 units, at age 6 months. At age 12 months, scores for those with periventricular leukomalacia were reduced by 11.9 units. Duration of hospital stay reduced scores by 0.1 for each additional day increase in hospital. Bronchopulmonary dysplasia constitutes a major cause of poor neuromotor outcomes at age 6 months, but improvements in motor outcomes occur over time.

Clinical Applications of Creatine Supplementation on Paediatrics

Creatine plays a central role in energy metabolism and is synthesized in the liver, kidney and pancreas. In healthy patients, it is transported via the blood stream to the muscles, heart and brain with high and fluctuating energy demands by the molecule creatine transporter. Creatine, although naturally synthesized in the human body, can be ingested in the form of supplements and is commonly used by athletes. The purpose of this review was to assess the clinical applications of creatine supplementation on paediatrics. Creatine metabolism disorders have so far been described at the level of two synthetic steps, guanidinoacetate N-methyltransferase (GAMT) and arginine: glycine amidinotransferase (AGAT), and at the level of the creatine transporter 1(CrT1). GAMT and AGAT deficiency respond positively to substitutive treatment with creatine monohydrate whereas in CrT1 defect, it is not able to replenish creatine in the brain with oral creatine supplementation. There are also data concerning the short and long-term therapeutic benefit of creatine supplementation in children and adults with gyrate atrophy (a result of the inborn error of metabolism with ornithine delta- aminotransferase activity), muscular dystrophy (facioscapulohumeral dystrophy, Becker dystrophy, Duchenne dystrophy and sarcoglycan deficient limb girdle muscular dystrophy), McArdles disease, Huntingtons disease and mitochondria-related diseases. Hypoxia and energy related brain pathologies (brain trauma, cerebral ischemia, prematurity) might benefit from Cr supplementation. This review covers also the basics of creatine metabolism and proposed mechanisms of action.

Haemostatic profile of healthy premature small for gestational age neonates

BACKGROUND The pathogenetic profile of premature Small for Gestational Age (SGA) neonates is strongly related to their haemostatic equilibrium, which is inadequately understood. OBJECTIVE To evaluate coagulation and fibrinolysis in premature SGA neonates before intervening with Vitamin K administration. STUDY DESIGN We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born prematurely [gestational age (G.A.) <37 weeks]. Study population consisted of 139 preterm newborns, 68 of whom were SGA (25 males and 43 females), while 71 were AGA (37 males and 34 females) that consisted the control group. Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, von Willebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test and the Mann-Whitney U test were used to compare the differences between the values of haemostatic parameters. RESULTS Premature SGA infants presented significantly lower levels of fibrinogen (p<0.029) and higher levels of VIIIc factor, APCR, tPA and PAI-1 (p<0.041, 0.017, 0.021 and 0.019 respectively). The two groups had similar demographic characteristics (except from birth weight), without significant differences in the values of other haemostatic parameters. CONCLUSIONS Despite the statistically significant differentiation in the levels of fibrinogen, VIIIc factor, APCR, tPA and PAI-1, the rest of haemostatic parameters have similar values between SGA and AGA preterms.

Neurological Outcome in Preterm Small for Gestational Age Infants Compared to Appropriate for Gestational Age Preterm at the Age of 18 Months: A Prospective Study

The aim of this study was to investigate the neurological outcome of premature small for gestational age infants at the corrected age of 18 months by the Hammersmith Infant Neurological Examination. A prospective trial was conducted comparing 41 preterm infants being small for gestational age with 41 appropriate for gestational age infants. Birth weight was significantly lower in small for gestational age infants compared with appropriate for gestational age infants (1724.6 ± 433 versus 1221 ± 328 g). There were no significant differences regarding the median gestational age and Apgar scores. Median global scores differ significantly between both groups: 75 (47-78) versus 76 (72-78) for the small for gestational age and appropriate for gestational age infants, respectively. Both groups had optimal scores. In conclusion, although the small for gestational age group scored lower in the Hammersmith Infant Neurological Examination, median global score in both groups was within optimal range.

Significant reduction of central line–associated bloodstream infection rates in a tertiary neonatal unit

To evaluate the effectiveness of a quality initiative in reducing central line-associated bloodstream infections (CLABSIs) in our neonatal intensive care unit, we designed a prospective study (January 2012-September 2013) estimating CLABSI incidence before and after our implementation. CLABSI rates were significantly decreased after our intervention, from 12 cases per 1,000 central vascular catheter (CVC) days during the preinterventional period to 3.4 cases per 1,000 CVC days during the postinterventional period (P = .004).

Intraventricular Hemorrhage and Platelet Indices in Extremely Premature Neonates.

Intraventricular hemorrhage (IVH) is a multifactorial disorder, the most important risk factors of which are prematurity and low birth weight. Disturbances in cerebral blood flow, inherent fragility of the germinal matrix vasculature, and platelet/coagulation disturbances are the 3 major pathogenic mechanisms. In this context, we investigated the role of platelet indices and several maternal and neonatal characteristics in the development of IVH through a retrospective cohort analysis of 130 extremely premature neonates, 24% of whom presented with severe IVH. There was a significant difference in platelet counts between the IVH and the control group on the first day of life (P=0.046). Presence of IVH was linked with lower birth weight (P=0.006) and lower gestational age (P=0.001). Platelet count on the first day of life was positively correlated with survival (P=0.001) and, along with platelet mass, was indicative of the worst IVH grade recorded for each neonate (P=0.002 and 0.007, respectively). Prolonged prothrombin time was also correlated with IVH (P<0.001), but factor analysis supported no prominent role. Maternal medications seem to play a minor role as well. In conclusion, IVH in extremely premature infants cannot be solely explained by platelet parameters, and further studies are required to determine the relationships between IVH, platelet indices, and outcomes.