Ultrasound evaluation of diaphragm kinetics after minimally invasive surfactant administration.

PURPOSE: Concerns remain on different alveolar deposition of surfactant between LISA and INSURE methods. Ultrasound evaluation of diaphragm kinetics may provide clinical evidence on this issue, as indirect representation of the respiratory system compliance. METHODS: This was a prospective-observational pilot study. The inclusion criterion was CPAP-supported infants ≤ 32 weeks with RDS receiving surfactant via minimally invasive technique. 52 patients randomized for surfactant administration via LISA or INSURE methods were enrolled. Right diaphragm (RD) global mean peak velocity (MPV) by Pulsed-Wave Tissue Doppler Imaging (PTDI) was recorded before and two hours after surfactant administration with simultaneous measurements of oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) (SF ratio). Mechanical ventilation ≤ 72 h from birth represented treatment failure. RESULTS: LISA infants had significantly higher gestational age (p = 0.029) and birth weight (p = 0.030) with lower CRIB-II scores (p = 0.030) than INSURE infants. LISA infants showed higher median MPV at baseline RD-PTDI US assessment (p = 0.024), but post-surfactant median MPV and other the investigated variables were similar at the adjusted analysis for gestational age and sedation. 8/52 (15%) infants who failed treatment had a significantly lower SF ratio (p = 0.002) and higher median MPV at RD-PTDI US (p = 0.004) after surfactant administration, despite the higher CPAP support level before (p = 0.007) and after (p = 0.001) surfactant administration. A full course of antenatal steroids was protective against mechanical ventilation (p = 0.038). CONCLUSIONS: Different minimally invasive surfactant administration techniques do not appear to influence diaphragm kinetics evaluated by RD-PTDI US.

Minipuberty assessment in newborns with hypoxic ischemic encephalopathy treated with therapeutic hypothermia: a single-center case-control study.

Introduction: The aim of our single-center case-control study is to evaluate whether minipuberty occurs in patients with hypoxic ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). We intend to conduct this evaluation by confronting the values of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and the values of testosterone in males and estradiol in females between newborns with HIE and in subsequent TH and healthy controls. Methods: We enrolled 40 patients (age: 56-179 days; 23 males), of whom 20 met the inclusion criteria for the case group and who underwent TH. A blood sample was taken from each patient at approximately 10 weeks of age to evaluate FSH and LH from the serum samples of all patients and to evaluate 17-beta estradiol (E2) and testosterone levels, respectively, from the serum samples of female and male patients. Results: It was found that minipuberty occurred in the case group patients, with no significant differences reported from the control group and with hormonal serum levels comparable to healthy infants of the control group (FSH 4.14 mUI/ml ± 5.81 SD vs. 3.45 mUI/ml ± 3.48 SD; LH 1.41 mUI/ml ±1.29 SD vs. 2.04 mUI/ml ±1.76 SD; testosterone in males 0.79 ng/ml ± 0.43 SD vs. 0.56 ng/ml ± 0.43 SD; 17-beta estradiol in females 28.90 pg/ml ± 16.71 SD vs. 23.66 pg/ml ± 21.29 SD). Discussion: The results of the present study may pave the way for further research and the evaluation of more possible advantages of TH.

Impact of blood sampling technique on reproducibility of viscoelastic coagulation monitor (VCM™) system test results in the neonate.

Purpose: To evaluate the reproducibility of the results of the viscoelastic coagulation test (VCT) performed with a new viscoelastic coagulation monitor (VCM™ - Entegrion) on native blood obtained by heel prick blood sampling with two different techniques compared to the standard blood collection in the newborn.Methods: Three blood samples were tested with the VCM analyzer in each of the 67 study subjects admitted to our level 3 neonatal intensive care unit. Standard blood collection (S) was performed by direct puncture of a peripheral vessel or by drawing of blood in a syringe connected to an arterial or venous catheter. Then, two more blood samples were drawn through a single heel prick. The first heel prick blood sample (HP1) was collected in the sample well through the attached metal capillary while the second (HP2) was poured directly into the sample well. Blood samples were automatically drawn into their pre-warmed cartridges and inserted into the VCM analyzers set up for analyses, which ran for one hour. VCT blood variables included clotting time (CT), clot formation time (CFT), angle alpha (α), amplitude at 10 and 20 min (A10 and A20), maximum clot firmness (MCF), and lysis indexes at 30 and 45 min (LY30 - LY45). Agreement was quantified by calculating the mean difference and SD between measurements of VCT blood variables from S, HP1 and HP2 blood samples. The 95% limits of agreement were calculated by the Bland & Altman method, using the upper or lower limit of agreement to interpret the variability of the measurements. The Kendall's τ correlation coefficient evaluated the interdependence between SD and intra-measurement mean.Results: S blood samples were easily obtained in all the study subjects, while mild difficulties were recorded in 3/67 infants (4.5%) with the HP1 blood sampling and in 5/67 infants (7%) with the HP2 blood sampling. Pairwise comparison of test results performed on blood samples drawn with HP1 and HP2 techniques showed moderate agreement for CT and α-angle, strong agreement for CFT, LY30 and LY45 and almost perfect agreement for A10, A20 and MCF. In pairwise comparison of VCM analyses performed on blood samples drawn with S technique vs HP1 and HP2 techniques, Kendall's τ correlation coefficient was significant for CT (S vs HP1 and HP1 vs HP2), CFT (S vs HP1 and S vs HP2), α-angle (S vs HP1) and MCF (S vs HP1). This suggests that the measurement error depends on the extent of the measurement. The overall ICC for blood sampling techniques ranged from 0.289 to 0.879 with best agreement observed for CFT (strong) and for A10, A20 and MCF (almost perfect). The LY30 index was the least repeatable measurement (poor agreement). The VCM analysis performed on the blood sample drawn with the HP1 technique showed the best repeatability compared with that performed with the S blood-sampling technique.Conclusion. VCT test results performed with the VCM analyzer on native blood drawn by heel prick in neonates are comparable to those obtained from standard blood samples. This could allow for a widespread, real-time assessment of the overall bedside haemostasis of these small patients.

How to improve CPAP failure prediction in preterm infants with RDS: a pilot study.

We aimed to test the diagnostic accuracy in predicting continuous positive airway pressure (CPAP) failure in premature infants with respiratory distress syndrome (RDS) by integrating oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) (SF ratio) with the measurement of peak velocity of the right diaphragmatic excursions (RD-PV), during the inspiration (I-Peak) and expiratory (E-Peak) phases, performed by pulsed-wave Tissue Doppler imaging. This is a prospective, observational pilot study conducted over a 2-year period. Neonates at ≤ 32 weeks gestation supported by early CPAP were eligible. Natural surfactant was delivered via a minimally invasive technique. We performed serial measurements of SF ratio and RD-PV during the early post-natal hours to test the accuracy in predicting surfactant administration as well as invasive ventilation support within 72 h from birth because of the RDS worsening. Of 56 preterm infants enrolled, 34 (61%) failed CPAP support. SF ratio showed a significant inverse relationship with both Silverman-Andersen score at birth (rho = - 0.417; P = .001) and RD-PV [E-Peak] (rho = - 0.361; P = .007). We achieved a high accuracy in predicting CPAP failure (AUC = 95%; 95% CI, 89-100%) by integrating gender, SF ratio, and RD-PV [E-Peak] at the restricted, multivariate analysis.Conclusions: SF ratio and RD-PV, as measured by pulsed-wave Tissue Doppler, may help physicians to improve their confidence in optimizing therapeutic options in preterm infants with RDS. What is Known: • Continuous positive airway pressure is the recommended first-line treatment for respiratory distress syndrome in preterm infants, but failure rates remain unacceptably high. • Choosing the optimal treatment in terms of non-invasive ventilation effectiveness and timeliness of surfactant administration for these patients is often challenging, also due to our inability to identify a worsening respiratory failure. What is New: • The integration of oxygen saturation, as measured by SpO2/FiO2, with right diaphragm peak motion velocities, as measured by pulsed-wave tissue Doppler, allows for high prediction accuracy of non-invasive ventilation support failure in premature infants at risk of respiratory distress syndrome. • These measurements may help physicians in providing optimal supportive therapy for these patients.

Cerebral Sinovenous Thrombosis in the Asphyxiated Cooled Infants: A Prospective Observational Study.

BACKGROUND: Cerebral sinovenous thrombosis is unusual in the asphyxiated cooled infants, but reliable data regarding the incidence of this comorbidity are lacking. We assessed the incidence of sinovenous thrombosis in a population of asphyxiated cooled infants by performing routine brain magnetic resonance venography. METHODS: All asphyxiated infants who underwent therapeutic cooling at our institution completed brain magnetic resonance venography after rewarming. Assessing the incidence of cerebral sinovenous thrombosis was the primary goal. Secondary analyses included group comparisons for laboratory tests and monitored parameters, relationship between variables, logistic regression models, and receiver operating characteristic curve for cerebral sinovenous thrombosis prediction. RESULTS: Cerebral sinovenous thrombosis was detected in 10 of 37 infants (27%), most commonly affecting the superior sagittal sinus (eight of ten). These infants manifested higher blanket (P < 0.001) and lower esophageal temperatures (P = 0.006), lower platelet counts (P = 0.045), and received more red blood cell transfusions (P = 0.038) than the cooled infants without thrombosis. Blanket temperature was independently associated with cerebral sinovenous thrombosis (P = 0.049), and 32°C/hour was the optimal cutoff value to predict the event (sensitivity, 90%; specificity, 88.5%). CONCLUSIONS: High incidence or cerebral sinovenous thrombosis in neonates treated with therapeutic hypothermia suggests that magnetic resonance venography may be reasonable in many of these children. High blanket temperature may be one variable that helps identify patients at higher risk.

Thromboelastographic profiles of the premature infants with and without intracranial hemorrhage at birth: a pilot study.

OBJECTIVE: To delineate thromboelastographic profiles of the premature infants with and without intracranial hemorrhage during the first 21 days of life. METHODS: In this study, 49 premature infants (24 female; 25 male) were consecutively admitted at our neonatal intensive care unit during a 6 months period were subject to thromboelastography and standard coagulation assessments at birth and weekly up to 21 days. Sixteen out of 49 infants developed intracranial hemorrhage at birth. RESULTS: The test results of 127/196 were considered eligible for analysis. Overall significant changes of the main thromboelastographic parameters were observed shortly after birth. Newborns with intracranial hemorrhage showed increased thromboelastogram-defined thrombin generation (shorter R and time to maximum amplitude times) from birth onward, suggesting a hypercoagulable state. No significant differences concerning thromboelastographic and coagulation assays parameters were found at birth between infants with and without intracranial hemorrhage, except for higher plasma D-Dimer concentration (p = 0.002) in the former infants. Finally, a positive correlation between clot lysis time and gestational age (Spearman's rho = 0.502, p = 0.002) was observed. CONCLUSIONS: Thromboelastographic profiles of the premature infants suggest an effective hemostatic function during the first post-natal weeks. Further study is needed to determine whether thromboelastography may be more useful than coagulation assays to reflect the bleeding risk of the premature infants.

Fresh frozen plasma use in the NICU: a prospective, observational, multicentred study.

OBJECTIVES: To examine the use of fresh frozen plasma (FFP) in Italian neonatal intensive care units (NICUs); specifically to quantify compliance with guideline recommendations and to evaluate the relationship between coagulation tests and subsequent bleeding episodes. DESIGN: Prospective, observational study. SETTING: Seventeen Italian NICUs. PATIENTS AND METHODS: Over a period of 12 months, for all neonates that received FFP we recorded specific characteristics, pretransfusion and post-transfusion laboratory test of haemostasis, and details of all haemorrhagic events. RESULTS: Among 3506 NICU admissions, 290 (8.2%) received one or more FFP transfusions during their hospital stay. Of these, 37% received FFP because of active bleeding and 63% received FFP prophylactically with the intention of preventing haemorrhage. A total of 609 FFP transfusions were administered (mean 2.1/transfused patient-range 1-25). Using previously agreed upon criteria, we judged that 60% of the 609 FFP transfusions were not compliant with guideline recommendations. By logistic regression, abnormalities in the prothrombin time, activated partial thromboplastin time, fibrinogen and platelet count were not independently associated with bleeding episodes. CONCLUSIONS: FFP transfusion is a relatively frequent intervention in the NICU. In the present analysis, we found a remarkably high proportion of FFP transfusions given to non-bleeding neonates for indications not compliant with guideline recommendations. Platelet counts and coagulation studies were poor predictors of clinical bleeding.

Symptomatic Meckel's diverticulum in newborn: two interesting additional cases and review of literature.

OBJECTIVES: This study aimed to review the literature about symptomatic Meckel's diverticulum (MD) in the neonatal period with 2 additional uncommon cases. METHODS: The authors describe 2 interesting neonatal cases of symptomatic MD and analyze the literature on this topic, with particular reference to the prevalence of sex, age at presentation, most common signs and symptoms, treatment, histology, associated anomalies, and outcome. RESULTS: The first patient was a term newborn with bowel obstruction by a pseudocystic MD. The second patient was a preterm infant with double perforation of the MD and ileum. Literature search for published case reports and case series on this topic reveals only 18 cases of neonatal symptomatic MD. Males are more frequently involved than females, and even preterm infants may be affected. Bowel obstruction (58.3%) and pneumoperitoneum (33.3%) are the most frequent clinical manifestation. Acute inflammation of the MD is the prominent histopathological finding (75%), although it does not seem to be related with the presence of heterotopic tissue within the MD. Surgical treatment is essential. The association of neonatal symptomatic MD with other anomalies is exceptional but is otherwise life threatening despite surgery. CONCLUSIONS: Bowel obstruction and pneumoperitoneum are the most frequent clinical manifestations of symptomatic MD in the newborn. Surgery is required for a definitive diagnosis and successful outcome.

A consistent approach to platelet transfusion in the NICU.

Platelet transfusions are the principal means of treating thrombocytopenia in neonatal intensive care units (NICUs), and are generally used as treatment of thrombocytopenic neonates who have active bleeding and as prophylactic administration in thrombocytopenic neonates who do not have hemorrhage but appear to be at high risk for bleeding. In this article, we summarize the rationale, benefits and risks of platelet transfusions in neonates. We review the importance of choosing the best product available for platelet transfusion, and we emphasize the importance of adopting and adhering to transfusion guidelines.

Functional echocardiographic assessment of myocardial performance in anemic premature infants: a pilot study.

This prospective observational study conducted in a neonatal intensive care unit aimed to evaluate echocardiographic changes provoked by anemia and transfusion of packed red blood cells (pRBCs) in premature infants. In this study, 32 anemic premature infants had serial echocardiographic assessment of left ventricular (LV) systolic performance, LV preload, and afterload immediately before, within 48 h, and up to 120 h after the transfusion of pRBCs. Pretransfusional evaluations also were compared with similar assessments of 71 nonanemic inpatient premature infants analogous for sex, gestational age at birth, and postnatal age. Left ventricular systolic performance was estimated from fractional shortening, LV output, and LV myocardial performance index (LVMPI). The LV preload was estimated from the LV end-diastolic dimension and the ratio of left atrium-to-aortic root dimension (LA/Ao ratio). The LV afterload was estimated from end-systolic wall stress. The LVMPI was found to decrease with increasing corrected gestational age in both the nonanemic (R = 0.173; p = 0.03) and anemic (R = 0.460; p = 0.007) infants. The LVMPI was the only index that changed after transfusion of pRBCs, decreasing in the younger anemic infants (p = 0.011) and increasing in the older anemic infants (p = 0.012). Finally, a significant inverse relationship between pre- and posttransfusional LVMPI values (R = 0.730; p < 0.001) was noted. The LVMPI may allow for identification of preterm infants more likely to be helped by transfusion of pRBCs.

Clinical use of fresh-frozen plasma and cryoprecipitate in neonatal intensive care unit.

Evidence-based indications for the use of plasma products in neonatal medicine are limited to few conditions. In the setting of inherited disorders of hemostasis, fresh frozen plasma (FFP) and cryoprecipitate should be used as replacement therapy only if the specific factor concentrate is not available. FFP is indicated to treat disseminated intravascular coagulation (DIC), liver failure, vitamin K-dependent bleeding and to reconstitute whole blood for exchange transfusion. Despite the lack of evidence, the use of cryoprecipitate to treat neonates with acquired hypofibrinogenemia during DIC or liver failure is now considered standard therapy.

Combination therapy for life-threatening pulmonary hypertension in a premature infant: first report on bosentan use.

Premature infants with preterm premature rupture of membranes (PPROM) are at high risk of severe respiratory failure because of lung hypodysplasia associated with persistent pulmonary hypertension of the newborn (PPHN). We describe the clinical course of a 28-week gestation infant with PPROM from the 20th week and prolonged oligohydramnios before delivery, who developed refractory hypoxia treated with oral bosentan as adjunct therapy to inhaled nitric oxide (iNO) and oral sildenafil. Conclusion Our experience suggests that bosentan can be used in the premature infant with PPHN after PPROM. To the best of our knowledge, this is the first report of bosentan treatment in a premature infant.

Changes in neonatal transfusion practice after dissemination of neonatal recommendations.

OBJECTIVE: To evaluate the change in neonatal transfusion practices after the introduction of national recommendations for transfusion of blood products to neonates in 2006. METHODS: A questionnaire-based survey on neonatal transfusion practice of 79 Italian NICUs was completed in 2008. Results were compared with those obtained from a previous national Italian neonatal transfusion-practice survey performed in 2001. RESULTS: Responses were received from 62 of 79 (78.5%) neonatal units. Prophylaxis for transfusion-transmitted cytomegalovirus infection in 2001 and 2008 had been performed in 96.8% and 98.4% of NICUs, respectively. Filter leukoreduction of red blood cell donor units was preferred over cytomegalovirus antibody testing to obtain cytomegalovirus-safe blood components. Prophylaxis for graft-versus-host disease increased from being performed at 61.3% of neonatal units in 2001 to 77.4% in 2008 (P = .08, Pearson chi(2)), whereas usage of dedicated red blood cell donor units (paedipack system), permitting multiple transfusions from the same unit, improved from 53.2% to 82.2% (P = .001, Pearson chi(2)). The 2008 survey documented a continuation of wide variability in transfusion practice for fresh-frozen plasma and platelet concentrates. CONCLUSIONS: This nation-wide Italian self-report survey highlighted improvements in NICU transfusion practice after the neonatal recommendations issued in 2006. Prophylaxis for transfusion-transmitted cytomegalovirus infection continued with nearly total adherence to national recommendations, and both prophylaxis for graft-versus-host disease and paedipack-system usage suggested a trend of improvement of adherence rates. The continuing wide diversity observed among neonatal units in fresh-frozen plasma and platelet-concentrate transfusion practice may indicate a lack of acceptable criteria for the administration of these blood products.

Cerebral arteriovenous shunts regression in two preterm newborns with heart failure in utero.

In this report, the cases of two newborn infants with cerebral arteriovenous shunts and heart failure in utero are presented. Different from the malformations of the vein of Galen, which usually generate a progressive and lethal heart failure after birth, our cases show heart failure resolution after birth, together with cerebral vascular shunt disappearance. Therefore, we hypothesized that the opening of arteriovenous shunts was a secondary modification due to the intrauterine heart failure. From our cases, it appears that, despite the dramatic echographic appearance, generalized cerebral venous dilatation can resolve spontaneously without sequelae.