Rita de Cássia dos Santos Silveira

Evaluation of interleukin‐6, tumour necrosis factor‐α and interleukin‐1β for early diagnosis of neonatal sepsis

Silveira RC, Procianoy RS. Evaluation of interleukin‐6, tumour necrosis factor‐α and interleukin‐1β for early diagnosis of neonatal sepsis. Acta Pædiatr 1999; 88: 647‐50. Stockholm. ISSN 0803‐5253

Hypothermia and Early Neonatal Mortality in Preterm Infants

OBJECTIVE To evaluate intervention practices associated with hypothermia at both 5 minutes after birth and at neonatal intensive care unit (NICU) admission and to determine whether hypothermia at NICU admission is associated with early neonatal death in preterm infants. STUDY DESIGN This prospective cohort included 1764 inborn neonates of 22-33 weeks without malformations admitted to 9 university NICUs from August 2010 through April 2012. All centers followed neonatal International Liaison Committee on Resuscitation recommendations for the stabilization and resuscitation in the delivery room (DR). Variables associated with hypothermia (axillary temperature <36.0 °C) 5 minutes after birth and at NICU admission, as well as those associated with early death, were analyzed by logistic regression. RESULTS Hypothermia 5 minutes after birth and at NICU admission was noted in 44% and 51%, respectively, with 6% of early neonatal deaths. Adjusted for confounding variables, practices associated with hypothermia at 5 minutes after birth were DR temperature <25 °C (OR 2.13, 95% CI 1.67-2.28), maternal temperature at delivery <36.0 °C (OR 1.93, 95% CI 1.49-2.51), and use of plastic bag/wrap (OR 0.53, 95% CI 0.40-0.70). The variables associated with hypothermia at NICU admission were DR temperature <25 °C (OR 1.44, 95% CI 1.10-1.88), respiratory support with cold air in the DR (OR 1.40, 95% CI 1.03-1.88) and during transport to NICU (OR 1.51, 95% CI 1.08-2.13), and cap use (OR 0.55, 95% CI 0.39-0.78). Hypothermia at NICU admission increased the chance of early neonatal death by 1.64-fold (95% CI 1.03-2.61). CONCLUSION Simple interventions, such as maintaining DR temperature >25 °C, reducing maternal hypothermia prior to delivery, providing plastic bags/wraps and caps for the newly born infants, and using warm resuscitation gases, may decrease hypothermia at NICU admission and improve early neonatal survival.

Massage therapy improves neurodevelopment outcome at two years corrected age for very low birth weight infants

BACKGROUND Long term effects of massage therapy in very preterm newborns infants are still to be described. Few studies evaluated neurodevelopment just at six months, and included late preterm infants. OBJECTIVE To study the effect of massage therapy on neurodevelopment of very low birth weight infants at two years corrected age. STUDY DESIGN Newborns with birth weight between >or= 750 and <or= 1500 g and gestational age <or= 32 weeks were randomly assigned to massage therapy by mothers plus skin-to-skin care (Intervention Group) or just skin-to-skin care (Control Group) during their hospital stay. Growth and neurodevelopment outcome were evaluated at 2 years corrected age. RESULTS We followed 73 newborns (35 in Intervention Group, and 38 in Control Group). Both groups were similar in neonatal data. Growth at 2 years corrected age was similar in both groups. Intervention Group had borderline higher Psychomotor Development Index and significantly higher Mental Development Index scores than Control Group. CONCLUSIONS We suggest that massage therapy by mothers combined to skin-to-skin care during neonatal hospital stay improves neurodevelopment outcome at 2 years corrected age.

Mechanical Ventilation of Newborns Infant Changes in Plasma Pro- and Anti-Inflammatory Cytokines

OBJECTIVE To evaluate plasma levels of interleukin (IL)-1beta, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha in newborn infants immediately before and after 2 hours of mechanical ventilation. STUDY DESIGN Term and late preterm neonates with no history of mechanical ventilation and/or ventilatory support were studied prospectively. Exclusion criteria were congenital malformations, congenital infections, use of nitric oxide, resuscitation with positive-pressure ventilation, and any procedure in the delivery room or neonatal intensive care unit that resulted in tracheal intubation. Blood samples for IL-1beta, IL-6, IL-8, IL-10, and TNF-alpha levels were collected before intubation and mechanical ventilation and 2 hours later. RESULTS Nineteen newborn infants with gestational age 35.8 +/- 1.9 weeks and birth weight 2280 +/- 370 g were included. Pro-inflammatory cytokines increased: IL-8 (2.5-fold), IL-1beta (7.5-fold), and TNF-alpha (10-fold), and the anti-inflammatory cytokine IL-10 decreased by 90%. Although median IL-6 levels were similar between before and after ventilation, IL-6 increased in 89.4% of infants. CONCLUSIONS A short period of mechanical ventilation promotes an imbalance of plasma levels of pro-inflammatory and anti-inflammatory cytokines. The systemic alteration of cytokines in response to mechanical ventilation may lead to ventilator-induced lung injury.

Association between high cytokine levels with white matter injury in preterm infants with sepsis.

Objective: To examine the association among interleukin-6, interleukin-8, tumor necrosis factor-&agr;, interleukin-10, and interleukin-1&bgr; and white matter injury in very-low-birth-weight infants with clinical sepsis and to help predict infants at risk for development of white matter injury. Design: A prospective cohort study was carried out. Setting: Neonatal intensive care unit. Patients: Very low birth weight infants with clinical early-onset sepsis. Exclusion criteria were death before 14 days, major malformations, and congenital infections. Intervention: Ultrasound brain scans were carried out on the third day and weekly until the sixth week of life or discharge and confirmed by a magnetic resonance image performed in the first year. Plasma was assayed for interleukin-6, interleukin-8, tumor necrosis factor-&agr;, interleukin-10, and interleukin-1&bgr; in the same sample collected for sepsis work-up. Mann-Whitney, chi-square, t tests, multiple regression, and receiver operating characteristic analysis were applied. Measurements and Main Results: From July 2005 to October 2007 we studied 84 very-low-birth-weight infants, 27 (32%) with white matter injury, and 57 (68%) control subjects (with no white matter injury). Proven early-onset sepsis and necrotizing enterocolitis were high risk for white matter injury after adjustment for gestational age and birth weight (relative risk, 3.04; 1.93–4.80 and relative risk, 2.2; 1.31–3.74, respectively). Interleukin-6, interleukin-8, and tumor necrosis factor-&agr; levels were higher in infants with white matter injury than in control subjects (p < .0001). Interleukin-1&bgr; and interleukin-10 were similar. The areas under the curve for interleukin-6, interleukin-8, and tumor necrosis factor-&agr; were 0.96 (0.92–0.99), 0.97 (0.94–1.0), and 0.93 (0.86–0.99), respectively. Interleukin-8 ≥100 pg/mL was the best predictor of white matter injury; the sensitivity and specificity were 96% and 83%, respectively, and negative predictive value was 98%. Conclusions: Very-low-birth-weight infants with proven early-onset sepsis, necrotizing enterocolitis, and high plasma levels of interleukin-6, interleukin-8, and tumor necrosis factor-&agr; are at high risk for white matter injury.

Growth and neurodevelopment outcome of very low birth weight infants delivered by preeclamptic mothers

Aim: To investigate growth and neurodevelopment outcome of very low birth weight (VLBW) infants delivered by preeclamptic mothers.

Ischemic brain damage in very low birth weight preterm newborn infants

OBJETIVO: Apresentar uma revisao critica e atualizada sobre as lesoes cerebrais isquemicas no recem-nascido pre-termo de muito baixo peso. FONTES DE DADOS: As referencias foram obtidas atraves do banco de dados MEDLINE, sendo selecionadas as mais representativas a criterio dos autores. SINTESE DOS DADOS: A hemorragia com evolucao para lesao isquemica cerebral, a leucomalacia periventricular cistica e a lesao difusa da substância branca cerebral sao as lesoes isquemicas mais frequentes em recem-nascidos pre-termo de muito baixo peso. Todas sao doencas de causas multifatoriais, em que podem estar envolvidos fatores vasculares, hemodinâmicos, inflamatorios e infecciosos. Sao doencas que podem causar sequelas neuropsicomotoras importantes e levar a paralisia cerebral e/ou deficit cognitivo e comportamental. CONCLUSOES: O diagnostico precoce e uma estrategia terapeutica adequada podem minimizar as sequelas causadas por essas doencas. A prevencao da prematuridade e a principal medida preventiva a ser tomada.

Maternal Preeclampsia Protects Preterm Infants against Severe Retinopathy of Prematurity

OBJECTIVE To study the influence of maternal preeclampsia on the occurrence of retinopathy of prematurity. STUDY DESIGN A prospective cohort study of 324 preterm neonates with birth weight ≤ 1500 g and gestational age ≤ 32 weeks. Multiple maternal and perinatal factors were analyzed for association and confounding by multiple logistic regression analysis. RESULTS Mean birth weight was 1128 ± 240 g, and mean gestational age 29.7 ± 1.9 weeks. Twenty-four newborns (7.4%) had severe retinopathy of prematurity; 97 had any stage of retinopathy, and 227 had no retinopathy of prematurity. Preeclampsia and complete antenatal steroid treatment course reduced the risk for any stage of retinopathy of prematurity by 60% and 54%, respectively. Preeclampsia reduced the risk for severe retinopathy of prematurity by 80%. CONCLUSIONS Preeclampsia lowered the risk for occurrence of any stage and severe retinopathy of prematurity in very low birth weight infants.

Assessment of the contribution of cytokine plasma levels to detect retinopathy of prematurity in very low birth weight infants.

PURPOSE To prospectively study the association of high cytokine plasma levels with later development of retinopathy of prematurity (ROP) in preterm infants with early-onset sepsis to assess a laboratory test to detect ROP. METHODS A prospective cohort study was conducted of preterm infants with clinical early-onset sepsis whose birth weight (BW) was ≤1500 g and gestational age (GA) was ≤32 weeks. Plasma samples were assayed for cytokines IL-6, IL-8, IL-10, IL-1β, and TNF-α. ROP was diagnosed in screening assessments. For the univariate analysis of the known risk factors for ROP, all infants without ROP were designated as the No ROP group, patients with any stage of ROP formed the ROP group, and all treated patients formed the Severe ROP group. The best cutoff points for all cytokine levels were determined by ROC curves. RESULTS Seventy-four patients were enrolled. Mean GA and BW were 29.6 ± 2.1 weeks and 1110.3 ± 232.5 g, respectively; 49 patients (66.2%) had no ROP and 25 (33.8%) had any stage of ROP (17 had stage 1 or 2 ROP and 8 had stage 3 ROP). IL-6 >357 pg/mL, IL-8 >216 pg/mL, and TNF-α >245 pg/mL were significantly associated with treatable ROP. CONCLUSIONS There is a relationship between high plasma levels of IL-6, IL-8, and TNF-α in the first days of life with the later development of ROP severe enough to treat in preterm infants with early-onset sepsis. Further epidemiologic studies are needed to explore other possible associations of high serum levels of cytokines with ROP in this population at high risk.

Periventricular leukomalacia in very low birth weight preterm neonates with high risk for neonatal sepsis

OBJECTIVE To investigate the association between periventricular leukomalacia (PVL) and neonatal sepsis in very low birth weight infants (VLBWI). METHODS We studied VLBWI with a clinical suspicion of infection who had been born at our institution between the 1st of August, 2005 and the 31st of July, 2007. Children were excluded if they died before reaching 14 days, had malformations of the central nervous system or congenital infections. Ultrasound brain scans were carried out on the third day and weekly up until the sixth week of life or discharge. Periventricular leukomalacia was diagnosed by persistent diffuse periventricular hyperechogenecity for more than 7 days, or by periventricular cysts. The VLBWI were separated into two groups on the basis of the presence or absence of PVL. Sepsis was defined as clinical manifestation plus a positive culture. The Mann-Whitney, chi-square and t tests were applied followed by logistic regression. RESULTS A total of 88 VLBWI were studied. Of these, 62 (70.5%) survived and 51 (57.8%) had PVL. Both groups were similar in terms of birth weight, gestational age, Apgar score, type of delivery, SNAPPE-II score, presence of necrotizing enterocolitis, persistent ductus arteriosus and deaths. Sepsis and mechanical ventilation were more common in the group with PVL (23.5 and 2.7%, p = 0.005; 86 and 59%, p = 0.004, respectively). Both of these were identified as, independent risk factors for PVL by logistic regression (p = 0.027 and 0.015, respectively). CONCLUSIONS Chorioamnionitis has been defined as a risk factor for PVL. We have demonstrated that neonatal sepsis is also an important risk factor. We believe that the systemic inflammatory response is the principal factor involved in the etiopathogenesis of PVL among VLBWI.