George Mitsiakos

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.

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.

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.

Influence of smoking during pregnancy on haemostasis in healthy full term neonates

BACKGROUND Clinical and experimental researches have linked smoking to disturbances of coagulation and fibrinolysis. Several potential mechanisms are incriminated involving inflammation, fibrinogen synthesis and clotting factors. Based on the fact that the majority of tobacco components cross the placental barrier, the objective of our current study is to investigate the influence of smoking during pregnancy on neonatal haemostasis. STUDY DESIGN The study was based on a comparative evaluation of coagulation and fibronolysis between healthy full term infants of women who smoked during pregnancy and a control group. Subjects consisted of 39 newborns of smoking and 43 newborns of nonsmoking mothers. Blood samples were obtained shortly after 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 (vWF), protein C and S, APCr, anti-thrombin (AT), t-PA and PAI-1. The independent t- test was used to compare the differences between the values of coagulation and fibrinolytic parameters at the p<0.05 level. RESULTS We discovered a statistically significant decrease in factor II and protein S levels and an elevation in t-PA and factor VIII concentrations in newborns of smoking mothers, without clinical manifestations of altered haemostasis. There were no significant differentiations in other coagulation or fibrinolytic parameters. CONCLUSION The alteration in factor II, protein S, t-PA and factor VIII in neonates exposed in utero to tobacco smoke is not accompanied by loss in the balance between coagulation and fibrinolytic pathways.

Focusing on patient safety in the Neonatal Intensive Care Unit environment

Patient safety in the Neonatal Intensive Care Unit (NICU) environment is an under-researched area, but recently seems to get high priority on the healthcare quality agenda worldwide. NICU, as a highly sensitive and technological driven environment, signals the importance for awareness in causation of mistakes and accidents. Adverse events and near misses that comprise the majority of human errors, cause morbidity often with devastating results, even death. Likewise in other organizations, errors causes are multiple and complex. Other high reliability organizations, such as air force and nuclear industry, offer examples of how standardized/homogenized work and removal of systems weaknesses can minimize errors. It is widely accepted that medical errors can be explained based on personal and/or system approach. The impact/effect of medical errors can be reduced when thorough/causative identification approach is followed by detailed analysis of consequences and prevention measures. NICU’s medical and nursing staff should be familiar with patient safety language, implement best practices, and support safety culture, maximizing efforts for reducing errors. Furthermore, top management commitment and support in developing patient safety culture is essential in order to assure the achievement of the desirable organizational safety outcomes. The aim of the paper is to review patient safety issues in the NICU environment, focusing on development and implementation of strategies, enhancing high quality standards for health care.

Corrigendum to “Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism”

In the paper titled “Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism,” [1] the first and last names of all the authors were reversed. The correct names in order (first name, last name) have been shown above.

Cerebral sinus thrombosis in an infant with Prader-Willi syndrome and literature review

A full-term male neonate from a first pregnancy of two clinical non-consanguineous parents was born at 40 weeks of gestation with cesarean section. He was admitted at 2 hours of life to our III level Neonatal Intensive Care Unit due to generalized hypotonia, presenting at birth. Cerebral ultrasound showed a temporal bilateral aspecific alteration of the parenchimal echogenicity, whereas a magnetic resonance imaging/venography revealed an extensive cerebral sinus thrombus. Extensive diagnostic studies for prothrombotic disorders showed negative results, even if there was an alterated haemostatic screening. Persistency of hypotonia led us to investigate Prader-Willi syndrome among others. Methylation analysis confirmed the diagnosis. This is the third report associating cerebral venous thrombosis and Prader-Willi syndrome, confirming sinus thrombosis as a possible presentation of this syndrome. A review of the literature is provided in order to disclose possible similarities and differences in Prader-Willi syndrome patients with cerebral sinovenus thrombosis.