Humberto Holmer Fiori

Hemispheric brain injury and behavioral deficits induced by severe neonatal hypoxia-ischemia in rats are not attenuated by intravenous administration of human umbilical cord blood cells.

Neonatal hypoxia-ischemia (HI) is an important cause of mortality and morbidity in infants. Human umbilical cord blood (HUCB) is a potential source of cellular therapy in perinatology. We investigated the effects of HUCB cells on spatial memory, motor performance, and brain morphologic changes in neonate rats submitted to HI. Seven-day-old rats underwent right carotid artery occlusion followed by exposure to 8% O2 inhalation for 2 h. Twenty-four hours after HI, rats received either saline solution or HUCB cells i.v. After 3 wk, rats were assessed using a Morris Water Maze and four motor tests. Subsequently, rats were killed for histologic, immunohistochemical, and polymerase chain reaction (PCR) analyses. HI rats showed significant spatial memory deficits and a volumetric decrease in the hemisphere ipsilateral to arterial occlusion. These deficits and decreases were not significantly attenuated by the injection of HUCB cells. Moreover, immunofluorescence and PCR analysis revealed few HUCB cells located in rat brain. Intravenous administration of HUCB cells requires optimization to achieve improved therapeutic outcomes in neonatal hypoxic-ischemic injury.

Red Blood Cell Transfusions are Independently Associated with Intra-Hospital Mortality in Very Low Birth Weight Preterm Infants

OBJECTIVE To test the hypothesis that red blood cell (RBC) transfusions in preterm infants are associated with increased intra-hospital mortality. STUDY DESIGN Variables associated with death were studied with Cox regression analysis in a prospective cohort of preterm infants with birth weight <1500 g in the Brazilian Network on Neonatal Research. Intra-hospital death and death after 28 days of life were analyzed as dependent variables. Independent variables were infant demographic and clinical characteristics and RBC transfusions. RESULTS Of 1077 infants, 574 (53.3%) received at least one RBC transfusion during the hospital stay. The mean number of transfusions per infant was 3.3 ± 3.4, with 2.1 ± 2.1 in the first 28 days of life. Intra-hospital death occurred in 299 neonates (27.8%), and 60 infants (5.6%) died after 28 days of life. After adjusting for confounders, the relative risk of death during hospital stay was 1.49 in infants who received at least one RBC transfusion in the first 28 days of life, compared with infants who did not receive a transfusion. The risk of death after 28 days of life was 1.89 times higher in infants who received more than two RBC transfusions during their hospital stay, compared with infants who received one or two transfusions. CONCLUSION Transfusion was associated with increased death, and transfusion guidelines should consider risks and benefits of transfusion.

Periodontal disease in pregnancy and low birth weight

Introduction: It is known for a long time that tooth and gingival infections may have long distance organic repercussions. Recently, it has been suggested that periodontal disease in pregnancy could be a cause of low weight at birth. Objective: To evaluate the influence of periodontal disease in pregnancy on the birth weight of the newborn infants. Patients and Methods: Mothers who gave birth to low-birth-weight infants were randomly selected (Group 1 - G1; n=13). Immediately after inclusion of each mother in group 1, the mother of the next term newborn with birth weight of > 2,500 g (Group 2 - G2; n=13) was included as control. Mothers were examined by a periodontist who was not informed of the group the child belonged to. A probe was used to measure attachment loss of the alveolar bone. The extension index (EI) and severity index (SI) of the periodontal disease were determined. Results: Both groups of mothers were similar in terms of maternal age, parity, color of skin, height, nutrition, smoking, drinking, socioeconomic status, prenatal examinations, premature rupture of membranes, chorioamnionitis, bacteriuria, placenta previa , abruptio placentae, previous hypertensive disease, preeclampsia, and heart disease. The characteristics of the newborns were: birth weight - G1 = 1,804 ± 675 g x G2 = 3,030 ± 516 g; gestational age - G1 = 33 ± 5 weeks x G2 = 39 ± 2 weeks; length of stay in the neonatal intensive care unit (NICU) - G1 = 128 days x G2 = 0 days. Average EI: G1 = 89.788 ± 18.355 x G2 = 72.420 ± 20.717; p=0.033. Average SI: G1 = 1.377 ± 0.626 x G2 = 0.754 ± 0.413 (OR=18.3; CI95%: 2.5-133.3; p = 0.006). After adjustment for risk factors for low birth weight, such as smoking, maternal height, bacteriuria, and previous hypertension, the odds ratio for SI dropped to 7.2 (CI95% = 0.4-125.4; P = 0.176). Conclusion: The multivariate analysis indicated a marked association between periodontal disease measured by SI score and low birth weight. Our data suggested that periodontal disease during pregnancy may be a risk factor for low weight at birth.

Surfactant Deficiency in Transient Tachypnea of the Newborn

OBJECTIVE To evaluate surfactant production and function in term neonates with transient tachypnea of the newborn (TTN). STUDY DESIGN Samples of gastric aspirates collected within 30 minutes of birth from 42 term newborns with gestational age ≥ 37 weeks (21 patients with TTN and 21 control subjects), delivered via elective cesarean delivery, were analyzed with lamellar body count and stable microbubble test. RESULTS Results of lamellar body counts and stable microbubble tests were significantly lower in the TTN group than in control subjects (P = .004 and .013, respectively). Lamellar body counts were significantly lower in infants with TTN requiring oxygen for ≥ 24 hours after birth than in infants requiring oxygen for < 24 hours (P = .029). When the cutoff point was 48 hours, the stable microbubble count was significantly lower in the group requiring oxygen for ≥ 48 hours than in the group requiring oxygen for < 48 hours (P = .047). CONCLUSIONS Term infants with TTN had low lamellar body counts associated with decreased surfactant function, suggesting that prolonged disease is associated with surfactant abnormalities.

Lamellar Body Count and Stable Microbubble Test on Gastric Aspirates from Preterm Infants for the Diagnosis of Respiratory Distress Syndrome

Background: Lamellar body count (LBC) in amniotic fluid is being used to identify infants at risk of respiratory distress syndrome (RDS) who would benefit from surfactant prophylaxis or very early therapy. The test in gastric aspirates of newborns has not been properly explored. Objective: The main objective of this research was to evaluate the performance of LBC alone or in combination with the stable microbubble test (SMT), done on gastric aspirates from preterm babies to predict RDS. Methods: A total of 34 preterm infants with RDS and 29 without RDS, with a gestational age between 24 and 34 weeks, were included in the study. Gastric fluid was collected in the delivery room. A diluent (dithiothreitol) allowed all samples to be processed, even the thickest and non-homogeneous ones, without centrifugation. The SMT was done for comparison. Results: The best cut-off value was <42,000 lamellar bodies/µl to predict RDS, with a sensitivity of 92% (95% CI 73–100%) and specificity of 86% (95% CI 77–95%). The area under the receiver-operating characteristic curve was 0.928 (95% CI 0.86–0.99). SMT showed similar results. LBC and SMT together in series (positive result if both tests were positive) showed a sensitivity of 100% and a specificity of 86%. Conclusion: LBC on gastric aspirates diluted in a solution of dithiothreitol can be rapidly and easily performed, and may be used alone or in combination with SMT as a predictor of RDS, allowing selective prophylaxis or very early treatment only in surfactant-deficient newborns.

Assessment of Vocal Fold Mobility Before and After Cardiothoracic Surgery in Children

OBJECTIVES To assess the incidence of vocal fold immobility (VFI) after cardiothoracic surgery in children and to determine the factors potentially associated with this outcome. METHODS Flexible laryngoscopy to assess vocal fold mobility was performed before surgery and within 72 hours after extubation in 100 pediatric patients who underwent cardiothoracic procedures. The 2 operating surgeons recorded the surgical technique and their impression of possible injury to the recurrent laryngeal nerve. The presence of laryngeal symptoms, such as stridor, hoarseness, and strength of cry, after extubation was documented. RESULTS Of 100 children included in this study, 8 had VFI after surgery. Univariate analyses showed that these 8 patients were younger and weighed less than the patients with normal vocal fold movement. Monopolar cautery was used in all patients with VFI. On univariate analysis, factors statistically significantly associated with VFI were circulatory arrest and dissection or ligation of the patent ductus arteriosus, left pulmonary artery, right pulmonary artery, or descending aorta. However, multivariate analyses failed to show these associations. CONCLUSIONS The incidence of VFI after cardiothoracic surgery in our population of children was 8.0% (8 of 100). Of several factors found to be potentially associated with VFI on univariate analysis, none were significant on multivariate analysis. This may be a result of the few patients with VFI. A larger multicenter prospective study would be needed to definitively identify factors associated with the outcome of VFI.

Evaluating end of life practices in ten Brazilian paediatric and adult intensive care units

Objective To evaluate the modes of death and treatment offered in the last 24 h of life to patients dying in 10 Brazilian intensive care units (ICUs) over a period of 2 years. Design and setting Cross-sectional, multicentre, retrospective study based on medical chart review. The medical records of all patients that died in seven paediatric and three adult ICUs belonging to university and tertiary hospitals over a period of 2 years were included. Deaths in the first 24 h of admission to the ICU and brain death were excluded. Intervention Two intensive care fellows of each ICU were trained in fulfilling a standard protocol (κ=0.9) to record demographic data and all medical management provided in the last 48 h of life. The Student t test, Mann–Whitney U test, χ2 test and RR were used for data comparison. Measurements and main results 1053 medical charts were included (59.4% adult patients). Life support limitation was more frequent in the adult group (86% vs 43.5%; p<0.001). A ‘do not resuscitate’ order was the most common life support limitation in both groups (75% and 66%), whereas withholding/withdrawing were more frequent in the paediatric group (33.9% vs 24.9%; p=0.02). The life support limitation was rarely reported in the medical chart in both groups (52.6% and 33.7%) with scarce family involvement in the decision making process (23.0% vs 8.7%; p<0.001). Conclusion Life support limitation decision making in Brazilian ICUs is predominantly centred on the medical perspective with scarce participation of the family, and consequently several non-coherent medical interventions are observed in patients with life support limitation.

Selective surfactant prophylaxis in preterm infants born at ≤31 weeks' gestation using the stable microbubble test in gastric aspirates

Abstract Objective: To evaluate the stable microbubble test (SMT) ability to select candidates for surfactant prophylaxis for respiratory distress syndrome (RDS). Study design: We followed patients treated according to a new routine for surfactant prophylaxis based on the SMT to determine timing of the initial dose of surfactant, proportion of infants using surfactant, and the predictive value of the SMT. Gastric secretions were collected after birth. Newborns with <25 microbubbles (MB)/mm2 received prophylactic surfactant. Surfactant was given only after confirmation of RDS (rescue therapy) to newborns with ≥25 MB/mm2. Results: Fifty-four (55%) had a low MB count and received prophylactic surfactant. Three out of 44 infants with a high MB count required rescue therapy (negative predictive value 93%; CI:81.3–98.6%). The median interval and interquartile range between surfactant administration and birth in the prophylaxis group was 20 (17–27) minutes. Surfactant was used in 23 of 28 (82%) infants born at <28 weeks of gestation and in 34 of 70 (49%) infants between 28 and 31 weeks. Conclusions: The SMT may be useful to determine surfactant prophylaxis (<30 min after birth). This approach may reduce costs and the number of unnecessary interventions.

Prospective operationalization and feasibility of a glycemic control protocol in critically ill children

Objective: To evaluate the feasibility and safe operationalization of a pediatric glycemic control protocol in the setting of a general pediatric intensive care unit in a developing country. Design: Prospective, observational cohort study carried out over 12 months. Setting: Fourteen-bed pediatric intensive care unit in Brazil. Patients: Children requiring mechanical ventilation with at least one organ system dysfunction were included. Interventions: Glucose was monitored and insulin used for persistent hyperglycemia (glucose >140 mg/dL [7.8 mmol/L] for at least two observations separated by at least a 1-hr interval), with a target glucose during insulin use of 60–140 mg/dL (3.3–7.8 mmol/L). Results: Out of 410 admissions, 144 children met the criteria for applying the protocol. One hundred fourteen of 144 (79%) children had at least one peak glucose level that was hyperglycemic, but only 44 (31%) children required insulin. Insulin infusion was most frequently started on day 1 (61%), with a glucose level at the time of 229 ± 79 mg/dL (12.7 ± 4.4 mmol/L). The mean glucose level after 6 hrs of insulin was 172 ± 87 mg/dL (9.6 ± 4.8 mmol/L), and the time to achieve the target glucose range was 9.5 (2–20) hrs (median [interquartile range]). The overall duration of insulin was 24.5 (10–48) hrs, and the average dose required was 0.06 ± 0.03 U/kg/hr. In the whole series, the peak glucose level was 202 ± 93 mg/dL (11.2 ± 5.2 mmol/L), with no difference between survivors and nonsurvivors. There was no difference in mortality when different glucose bands were considered and no association between glucose level and mortality. The overall rate of hypoglycemia (glucose <40 mg/dL [2.2 mmol/L]) was 8.3%, and it was more common in those receiving insulin (20% vs. 3%, p < .05). Conclusions: Hyperglycemia is frequent in critically ill children managed in a pediatric intensive care unit in a developing country. Using a glycemic control protocol, one-third of these children required insulin, but attendants should be aware of a significant risk of hypoglycemia in this setting. Based on these data, a trial to detect a 20% relative reduction in mortality (power 90%, p = .05) associated with insulin in a similar population would need to screen >10,000 patients.

Tadalafil improves oxygenation in a model of newborn pulmonary hypertension.

Objectives: Sildenafil, a phosphodiesterase-5 inhibitor, significantly improves oxygenation when used in animal models and patients with pulmonary hypertension. Tadalafil is a new and clinically available phosphodiesterase-5 inhibitor that, aside from causing pulmonary vasodilation, has been shown to increase cardiac output in pulmonary hypertensive adults. Its hemodynamic effects on the newborn, however, have not been tested. The objective was to evaluate the effect of tadalafil on central hemodynamics and arterial oxygenation in a piglet model of acute pulmonary hypertension. Design: Laboratory experiment. Setting: University laboratory. Subjects: Seven anesthetized and mechanically ventilated newborn piglets. Interventions: Pulmonary hypertension was induced and maintained in seven anesthetized and mechanically ventilated newborn piglets following acute exposure to 11% oxygen. The experimental animals received orla tadalafil (1 mg/kg), whereas the control animals were given an equal volume of normal saline. Systemic and pulmonary hemodynamic variables were measured, and the cardiac output and ejection fraction were obtained from two-dimensional echocardiogram and Doppler measurements in all animals. Serial arterial blood gases were also obtained, and the alveolar-arterial oxygen gradient was calculated. Measurements and Main Results: In contrast with the control animals, in which no significant changes were noted, in the experimental animals pulmonary arterial pressure decreased on average by 54% and cardiac output increased by 88% following tadalafil administration (p < .05). Tadalafil increased the Pao2 by 48% ± 21% (p < .01), likely as a result of a 74% ± 13% reduction in the alveolar-arterial oxygen gradient (p < .01). Conclusions: In a newborn animal model of acute pulmonary hypertension, oral tadalafil administration reduces pulmonary vascular resistance and increases arterial oxygenation by increasing cardiac output and reducing the lung shunt fraction. This previously untested compound deserves additional investigation in laboratory models of persistent pulmonary hypertension of the newborn.