Cláudia Regina Hentges

Association of late-onset neonatal sepsis with late neurodevelopment in the first two years of life of preterm infants with very low birth weight

OBJECTIVE To establish the influence of late-onset sepsis on neurodevelopment of preterm infants with very low birth weight (VLBW), according to the etiologic agent. METHOD This was a cohort of newborns with birth weight<1,500 g and gestational age less than 32 weeks, admitted to the institutional intensive care unit (ICU) with up to 48 hours of life, and followed-up at the outpatient follow-up clinic for preterm infants with VLBW until 2 years of corrected age. EXCLUSION CRITERIA death within the first 72 hours of life, congenital malformations and genetic syndromes, children with congenital infection by the human immunodeficiency virus (HIV), congenital infection (STORCH), presence of early-onset sepsis and cases with more than one pathogen growth in blood cultures. Septic and non-septic infants were compared regarding neonatal outcomes and mortality. Neurodevelopment was assessed using the Bayley Scale (BSDI-II) at 18 to 24 months of corrected age. RESULTS 411 preterm infants with VLBW were eligible; the mean gestational age was 29 ± 2.2 weeks and mean birth weight was 1,041 ± 281 grams. Late-onset sepsis occurred in 94 preterm infants with VLBW (22.8%). VLBW infants with Gram-positive infection showed motor deficit when compared to the non-septic group, 68.8% vs. 29.3%, respectively (OR 6; 1.6-21.8, p=0.006); the cognitive development was similar between the groups. The overall mortality rate from infection was 26.7%; considering the pathogens, the rates were 18.7% for coagulase-negative Staphylococcus, 21.8% for Gram-positive bacteria, and 50% for Gram-negative bacteria and fungi. CONCLUSION Neonatal sepsis has a significant influence on late neurodevelopment at 2 years of corrected age in preterm infants with VLBW, and Gram-positive infections are associated with motor deficit.

Serum levels of caffeine in umbilical cord and apnea of prematurity

OBJECTIVE To determine the influence of presence of caffeine in umbilical cord blood on apnea occurrence. METHODS A prospective cohort study with preterm newborns with birth weight lower than 2,000 g was undertaken. Exclusion criteria were: mothers who received opioids; mechanical ventilation during the first 4 days of life; cerebral and major cardiac malformations; perinatal asphyxia; severe periintraventricular hemorrhage; exchange transfusion before the fourth day of life; and those who received methylxanthine prior to extubation. Neonates were divided into detectable and undetectable caffeine in umbilical cord blood. Newborns were followed for the first 4 days for occurrence of apnea spells. RESULTS Eighty-seven newborns with and 40 without detectable caffeine in umbilical cord blood were studied. Median caffeine concentration of the 87 patients with detectable caffeine in umbilical blood was 2.3 microg/mL (0.2-9.4 microg/mL). There was no association between occurrence of apnea spells and presence of caffeine in umbilical cord blood. Neonates with detectable caffeine in umbilical blood had borderline later apnea (66.3+/-4.14 hours) than those with undetectable levels (54.2+/-6.26 hours). CONCLUSION Detected levels of caffeine in umbilical cord blood did not decrease occurrence of apnea of prematurity, but it had a borderline effect delaying its occurrence, suggesting that even a low level of caffeine in umbilical cord blood might delay occurrence of apnea spells.

Vascular Endothelial Growth Factor/Placental Growth Factor Heterodimer Levels in Preterm Infants with Bronchopulmonary Dysplasia

BACKGROUND Bronchopulmonary dysplasia (BPD) is associated with changes in pulmonary angiogenesis. However, the role of the vascular endothelial growth factor/placental growth factor (VEGF/PlGF) heterodimer, an antiangiogenic factor, remains unknown in this disease. OBJECTIVE To compare VEGF/PlGF levels in preterm infants with and without BPD. METHODS This study was approved by the Institutional Review Board. Preterm neonates with birth weight <2,000 g and gestational age ≤ 34 weeks were included. Exclusion criteria were: neonates transferred from other institutions after 72 hours of life; death before blood collection; presence of major congenital malformations, inborn errors of metabolism, and early sepsis; and mothers with multiple pregnancies, TORCH infections, HIV infection, or autoimmune diseases. BPD was defined as the need for oxygen therapy for a period equal to or greater than 28 days, accompanied by radiographic changes compatible with the disease. Blood was collected from neonates in the first 72 hours of life. VEGF/PlGF levels were measured using the enzyme-linked immunosorbent assay method. The chi-square test, t-test, Mann-Whitney test, analysis of variance, and Kruskal-Wallis test were used for statistical analysis. Variables found to be significant in the univariate analysis were included in the multivariate analysis. RESULTS Seventy-three patients were included (19 with BPD, 43 without BPD, and 11 neonates who died in the first 28 days of life), with a mean (SD) gestational age of 30.32 (2.88) weeks and birth weight of 1,288 (462) g. Median VEGF/PlGF levels were higher in the groups with BPD and death in the first 28 days of life than in the group without BPD (16.46 [IQR, 12.19-44.57] and 20.64 [IQR, 13.39-50.22], respectively, vs. 9.14 [IQR, 0.02-20.64] pg/mL], p < 0.001). Higher VEGF/P1GF levels remained associated with BPD and death in the first 28 days of life in the multivariate analysis. CONCLUSION Higher plasma VEGF/PlGF levels were found in preterm neonates with BPD and in those who died in the first 28 days of life, suggesting an important role of this substance in pulmonary vascular development.

Angiogenic and Antiangiogenic Factors in Preterm Neonates Born to Mothers with and without Preeclampsia

BACKGROUND Angiogenic and antiangiogenic factors are altered in pregnant women with preeclampsia (PE), but the pattern of expression of these factors in their newborns remains unknown. OBJECTIVE This study aims to measure vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) levels in preterm neonates born to mothers with PE. METHODS Neonates with birth weight<2,000 g and gestational age≤34 weeks were included and divided into the following two groups: born to mothers with PE and without PE. Blood was collected from neonates within the first 72 hours of life. VEGF and sFlt-1 levels were measured using the enzyme-linked immunosorbent assay method. RESULTS A total of 88 neonates were included (37 born to mothers with PE and 51 born to mothers without PE), with a mean gestational age of 29.12±2.96 weeks and birth weight of 1,223.80±417.48 g. In the multivariate analysis, VEGF was 80% lower and sFlt-1 was 13.48 times higher in the group with PE. sFlt-1 concentration was higher in neonates small for gestational age (SGA) than in those appropriate for gestational age. CONCLUSION Higher sFlt-1 and lower VEGF levels in the group with PE, as well as higher sFlt-1 levels in SGA neonates, reflect a predominance of antiangiogenic mechanisms in PE and growth restriction.

Infecção disseminada por Trichosporon spp em recém-nascido prematuro: relato de um caso

OBJECTIVE: To report the first case of disseminated Trichosporon spp infection in a newborn infant in Brazil, discussing a few aspects concerning management and treatment. A new spectrum of pathogens associated with severe infections in neonatal ICU has arisen, afflicting mainly newborn infants weighing less than 1,000 g at birth. Infection with Trichosporon asahii is rare and often fatal in this group of patients. DESCRIPTION: A case of Trichosporon spp fatal infection in a newborn weighing 815 g at birth is reported. Literature search in the main databases returned only nine articles, reporting 14 cases of infection with this fungus in preterm newborns. CONCLUSIONS: The rate of invasive fungal infection is around 6% in this group of patients, Trichosporon infection being a likely occurrence. Mortality rate in these cases is extremely high, but early treatment with triazole antifungals improves prognosis significantly.

Níveis plasmáticos de cafeína no cordão umbilical e apneia da prematuridade

OBJECTIVE: To determine the influence of presence of caffeine in umbilical cord blood on apnea occurrence. METHODS: A prospective cohort study with preterm newborns with birth weight lower than 2,000 g was undertaken. Exclusion criteria were: mothers who received opioids; mechanical ventilation during the first 4 days of life; cerebral and major cardiac malformations; perinatal asphyxia; severe periintraventricular hemorrhage; exchange transfusion before the fourth day of life; and those who received methylxantine prior to extubation. Neonates were divided into detectable and undetectable caffeine in umbilical cord blood. Newborns were followed for the first 4 days for occurrence of apnea spells. RESULTS: Eighty-seven newborns with and 40 without detectable caffeine in umbilical cord blood were studied. Median caffeine concentration of the 87 patients with detectable caffeine in umbilical blood was 2.3 µg/mL (0.2-9.4 µg/mL). There was no association between occurrence of apnea spells and presence of caffeine in umbilical cord blood. Neonates with detectable caffeine in umbilical blood had borderline later apnea (66.3±4.14 hours) than those with undetectable levels (54.2±6.26 hours). CONCLUSION: Detected levels of caffeine in umbilical cord blood did not decrease occurrence of apnea of prematurity, but it had a borderline effect delaying its occurrence, suggesting that even a low level of caffeine in umbilical cord blood might delay occurrence of apnea spells.

Disseminated Trichosporon spp infection in preterm newborns: a case report

OBJECTIVE To report the first case of disseminated Trichosporon spp infection in a newborn infant in Brazil, discussing a few aspects concerning management and treatment. A new spectrum of pathogens associated with severe infections in neonatal ICU has arisen, afflicting mainly newborn infants weighing less than 1,000 g at birth. Infection with Trichosporon asahii is rare and often fatal in this group of patients. DESCRIPTION A case of Trichosporon spp fatal infection in a newborn weighing 815 g at birth is reported. Literature search in the main databases returned only nine articles, reporting 14 cases of infection with this fungus in preterm newborns. CONCLUSIONS The rate of invasive fungal infection is around 6% in this group of patients, Trichosporon infection being a likely occurrence. Mortality rate in these cases is extremely high, but early treatment with triazole antifungals improves prognosis significantly.

Influence of maternal pre-eclampsia on VEGF/PlGF heterodimer levels in preterm infants

Abstract Objective: To measure VEGF/PlGF heterodimer levels in preterm infants born to mothers with preeclampsia. Methods: Neonates with birth weight <2000 g and gestational age ≤34 weeks were divided into two groups: born to mothers with Preeclampsia (PE) and controls. Neonates transferred from outside after the 72nd hour of life, death before blood collection, major congenital malformations or inborn errors of metabolism, and mothers with multiple pregnancies, STORCH complex infections, HIV or autoimmune conditions were excluded. Blood was collected within 72 h of birth and again at 28 days. VEGF/PlGF heterodimer levels were measured by ELISA. Results: We included 73 neonates (24 born to mothers with PE and 49 without PE). Mean gestational age was 30.32 ± 2.88 weeks and mean birth weight was 1288.62 ± 462.22 g. Median VEGF/PlGF levels were significantly higher in infants born to mothers with PE. VEGF/PlGF levels were inversely proportional to birth weight. There were no between-group differences in blood samples collected at age 28 days. Conclusion: Higher VEGF/PlGF levels were higher in neonates exposed to PE, and there was a significant negative correlation between birth weight and VEGF/PlGF levels. Further studies to elucidate the role of this substance in the fetal and neonatal period are needed.