Proactive management of extreme prematurity: disagreement between obstetricians and neonatologists.

OBJECTIVE: To verify, in extremely preterm infants, if disagreement between obstetricians and neonatologists regarding proactive management is associated with early death. STUDY DESIGN: Prospective cohort of 484 infants with 23(0/7) to 26(6/7) weeks, without malformations, born from January 2006 to December 2009 in eight Brazilian hospitals. Pro-active management was defined as indication of ≥1 dose of antenatal steroid or cesarean section (obstetrician) and resuscitation at birth according to the international guidelines (neonatologist). Main outcome was neonatal death in the first 24 h of life. RESULT: Obstetricians and neonatologists disagreed in 115 (24%) patients: only neonatologists were proactive in 107 of them. Disagreement between professionals increased 2.39 times the chance of death in the first day (95% confidence interval 1.40 to 4.09), adjusted for center and maternal/neonatal clinical conditions. CONCLUSION: In infants with 23 to 26 weeks of gestation, disagreement between obstetricians and neonatologists, translated as lack of antenatal steroids and/or vaginal delivery, despite resuscitation procedures, increases the odds of death in the first day.

A predictive score for retinopathy of prematurity in very low birth weight preterm infants.

AIMS: This study describes the development of a score based on cumulative risk factors for the prediction of severe retinopathy of prematurity (ROP) comparing the performance of the score against the birth weight (BW) and gestational age (GA) in order to predict the onset of ROP. METHODS: A prospective cohort of preterm infants with BW≤ 1500 g and/or GA≤ 32 weeks was studied. The score was developed based on BW, GA, proportional weight gain from birth to the 6th week of life, use of oxygen in mechanical ventilation, and need for blood transfusions from birth to the 6th week of life. The score was established after linear regression, considering the impact of each variable on the occurrences of any stage and severe ROP. Receiver operating characteristic (ROC) curves were used to determine the best sensitivity and specificity values for the score. All variables were entered into an Excel spreadsheet (Microsoft) for practical use by ophthalmologists during screening sessions. RESULTS: The sample included 474 patients. The area under the ROC curve for the score was 0.77 and 0.88 to predict any stage and severe ROP, respectively. These values were significantly higher for the score than for BW (0.71) and GA (0.69) when measured separately. CONCLUSIONS: ROPScore is an excellent index of neonatal risk factors for ROP, which is easy to record and more accurate than BW and GA to predict any stage ROP or severe ROP in preterm infants. The scoring system is simple enough to be routinely used by ophthalmologists during screening examination for detection of ROP.

Cerebellar growth in very low birth weight infants.

OBJECTIVE: The aim of this study was to assess cerebellar growth of very low birth weight infants from birth to discharge and compare it with term infants. STUDY DESIGN: Very low birth weight infants were matched by gender, adequacy of weight to gestational age at birth and postmenstrual ages at hospital discharge to term newborns. Exclusion criteria were central nervous system malformation, peri-intraventricular hemorrhage, cerebellar hemorrhage and meningitis. Transverse cerebellar diameter was measured by cranial ultrasound at birth and at hospital discharge in cases, and at birth in matched controls. Very low birth weight infants had magnetic resonance imaging done in the first year. RESULT: Cerebellar growth was similar in very low birth weight infants without periventricular leukomalacia and controls, and smaller in cases with periventricular leukomalacia than in controls. CONCLUSION: We suggest that cerebellar growth is normal in the absence of supratentorial injury.

Score for Neonatal Acute Physiology and Perinatal Extension II as a predictor of retinopathy of prematurity: study in 304 very-low-birth-weight preterm infants.

AIM: To evaluate the use of the Score for Neonatal Acute Physiology and Perinatal Extension (SNAPPE-II) at admission to predict the development of retinopathy of prematurity (ROP) among very-low-birth-weight preterm babies. METHODS: A prospective cohort study included 304 infants screened for ROP from July 2004 to October 2007. The main outcomes were the development of any stage ROP and severe ROP. The main variable was the SNAPPE-II obtained at admission. Seventeen risk factors for ROP were studied by univariate analysis (chi(2) and Student's t test). A simple descriptive analysis was used for the SNAPPE-II (mean, median, standard deviation and interquartile range: p25-p75). Logistic regression and receiver-operating characteristic (ROC) curve were calculated for SNAPPE-II. Ophthalmological examinations started at the 6th week of life and were repeated until the 45th week of corrected gestational age (GA). RESULTS: The mean GA and mean birth weight of the whole cohort were 30.3 weeks (+/-2.2) and 1,209.2 g (+/-277.7), respectively. The median SNAPPE-II among non-ROP and ROP patients were 6.0 and 15.0, respectively (p = 0.001). When compared with severe ROP patients (25.0) there was also a significant difference (p = 0.003). After logistic regression, the SNAPPE-II adjusted odds ratio for ROP was 1.024. The area under the ROC curve was 0.62 (95% confidence interval: 0.55-0.70, p < 0.001). The best discriminative cutoff value was 8.5 (sensitivity: 68%; specificity: 54%; positive predictive value: 37.3%; negative predictive value: 80.6%). CONCLUSIONS: The SNAPPE-II values at admission were significantly higher among babies with ROP, suggesting a positive association between higher scores with the development of ROP, but after adjusted logistic regression and ROC curve results, the SNAPPE-II scores at admission did not enhance the assessment of risk for ROP.

Incidence and risk factors for retinopathy of prematurity in very low and in extremely low birth weight infants in a unit-based approach in southern Brazil.

AIMS: To analyse the incidence and risk factors for retinopathy of prematurity (ROP) and survival rates among extremely low birth weight (ELBW) and very low birth weight (VLBW) preterm infants. METHODS: A prospective cohort study of 352 infants admitted at a teaching hospital, Hospital de Clinicas de Porto Alegre, Brazil, between October 2002 and December 2006, was screened for ROP. The ELBW group comprised infants whose birth weight (BW) was < or = 1000 g and the VLBW group comprised those infants whose BW were > 1000 g and < or = 1500 g. Perinatal risk factors for ROP were assessed using univariate and multivariate analysis. RESULTS: Of the 352 neonates screened, 88 were ELBW babies. Survival rates among ELBW and VLBW were 47.8 and 88.7%, respectively. ROP affected 48.9% of ELBW infants and 18.2% of VLBW babies. Threshold disease occurred in 21 patients, 15 of whom were born weighing < 1000 g. Only 2.3% of the neonates born with more than 1000 g developed treatable disease. Univariate analysis showed that gestational age (GA), BW, use of indomethacin and erythropoietin, blood transfusions, and intraventricular haemorrhage were associated with ROP. After logistic regression, the most important adjusted risk factors were BW (OR: 1.002;95% CI: 1.001-1.003; P=0.003), GA (OR: 1.254;95% CI: 1.082-1.455; P=0.003), and use of erythropoietin (OR: 2.486;95% CI: 1.182-5.231; P=0.016). CONCLUSION: This study showed reduced survival rates, high incidence of ROP, and a greater need of treatment among ELBW infants as compared to VLBW babies admitted in this institution.

Massage therapy reduces hospital stay and occurrence of late-onset sepsis in very preterm neonates.

OBJECTIVE: To study the effect of maternal massage therapy on hospital stay in very-low-birth-weight infants who were already submitted to skin-to-skin care. STUDY DESIGN: A randomized study was performed including infants of birth weight >or=750 and

Cortisol and 17-alpha-hydroxy-progesterone levels in infants with refractory hypotension born at 30 weeks of gestation or less.

Refractory hypotension is frequent in very low-birth weight infants, whose hypothalamic-pituitary-adrenal axis has been suggested to be immature. The objective of the present study was to evaluate basal cortisol and 17-alpha-OH-progesterone in the first 36 h of life in preterm infants with and without refractory hypotension (mean arterial blood pressure below the lower limit for gestational age throughout the study despite aggressive volume expansion and use of vasopressors). Thirty-five infants with

Cortisol and 17-a-hydroxy-progesterone levels in infants with refractory hypotension born at 30 weeks of gestation or less

Refractory hypotension is frequent in very low-birth weight infants, whose hypothalamic-pituitary-adrenal axis has been suggested to be immature. The objective of the present study was to evaluate basal cortisol and 17-a-OH-progesterone in the first 36 h of life in preterm infants with and without refractory hypotension (mean arterial blood pressure below the lower limit for gestational age throughout the study despite aggressive volume expansion and use of vasopressors). Thirty-five infants with ú30 weeks of gestation and a birth weight ú1250 g, with no postnatal use of corticosteroid or death in the first 48 h were studied. Mean arterial pressure was measured every 4 h during the first 48 h. Cortisol and 17-a-OH-progesterone were determined at 12 and 36 h and patients were divided into refractory hypotensive (N = 15) and control (N = 20) groups. The groups were not different regarding type of delivery, use of prenatal corticosteroid, requirement of mechanical ventilation, use of vasopressor drugs, morphine, fentanyl, prophylactic indomethacin, and mean sample timing. Although refractory hypotensive newborns were more immature, were smaller, suffered more deaths after 48 h of life and had a higher SNAPPE-2 score, their cortisol and 17-a-OH-progesterone levels were not different from controls at 12 h and at 36 h. The increase of cortisol in newborns with refractory hypotension 36 h after birth was significantly higher than in controls. Despite the fact that refractory hypotensive very low-birth weight neonates were submitted to a very stressful condition, their cortisol and 17-a-OH-progesterone levels were similar to controls.

Umbilical cord blood and neonatal endothelin-1 levels in preterm newborns with and without respiratory distress syndrome.

Increased pulmonary vascular resistance in preterm newborn infants with respiratory distress syndrome is suggested, and endothelin-1 plays an important role in pulmonary vascular reactivity in newborns. We determined umbilical cord blood and neonatal (second sample) levels of endothelin-1 in 18 preterm newborns with respiratory distress syndrome who had no clinical or echocardiographic diagnosis of pulmonary hypertension and 22 without respiratory distress syndrome (gestational ages: 31.4 +/- 1.6 and 29.3 +/- 2.3 weeks, respectively). Umbilical cord blood and a second blood sample taken 18 to 40 h after birth were used for endothelin-1 determination by enzyme immunoassay. Median umbilical cord blood endothelin-1 levels were similar in both groups (control: 10.9 and respiratory distress syndrome: 11.4 pg/mL) and were significantly higher than in the second sample (control: 1.7 pg/mL and respiratory distress syndrome: 3.5 pg/mL, P < 0.001 for both groups). Median endothelin-1 levels in the second sample were significantly higher in children with respiratory distress syndrome than in control infants (P < 0.001). There were significant positive correlations between second sample endothelin-1 and Score for Neonatal Acute Physiology and Perinatal Extension II (r = 0.36, P = 0.02), and duration of mechanical ventilation (r = 0.64, P = 0.02). A slower decline of endothelin-1 from birth to 40 h of life was observed in newborns with respiratory distress syndrome when compared to controls. A significant correlation between neonatal endothelin-1 levels and some illness-severity signs suggests that endothelin-1 plays a role in the natural course of respiratory distress syndrome in preterm newborns.

Umbilical cord blood and neonatal endothelin-1 levels in preterm newborns with and without respiratory distress syndrome

Increased pulmonary vascular resistance in preterm newborn infants with respiratory distress syndrome is suggested, and endothelin-1 plays an important role in pulmonary vascular reactivity in newborns. We determined umbilical cord blood and neonatal (second sample) levels of endothelin-1 in 18 preterm newborns with respiratory distress syndrome who had no clinical or echocardiographic diagnosis of pulmonary hypertension and 22 without respiratory distress syndrome (gestational ages: 31.4 ± 1.6 and 29.3 ± 2.3 weeks, respectively). Umbilical cord blood and a second blood sample taken 18 to 40 h after birth were used for endothelin-1 determination by enzyme immunoassay. Median umbilical cord blood endothelin-1 levels were similar in both groups (control: 10.9 and respiratory distress syndrome: 11.4 pg/mL) and were significantly higher than in the second sample (control: 1.7 pg/mL and respiratory distress syndrome: 3.5 pg/mL, P < 0.001 for both groups). Median endothelin-1 levels in the second sample were significantly higher in children with respiratory distress syndrome than in control infants (P < 0.001). There were significant positive correlations between second sample endothelin-1 and Score for Neonatal Acute Physiology and Perinatal Extension II (r = 0.36, P = 0.02), and duration of mechanical ventilation (r = 0.64, P = 0.02). A slower decline of endothelin-1 from birth to 40 h of life was observed in newborns with respiratory distress syndrome when compared to controls. A significant correlation between neonatal endothelin-1 levels and some illness-severity signs suggests that endothelin-1 plays a role in the natural course of respiratory distress syndrome in preterm newborns.

Effect of perinatal asphyxia on thyroid-stimulating hormone and thyroid hormone levels.

AIM: To compare serum concentrations of thyroid hormones--T4, T3, free T4 (FT4) and reverse T3 (rT3)--and thyroid-stimulating hormone (TSH) found in the umbilical cord blood of term newborns with and without asphyxia and those found in their arterial blood collected between 18 and 24 h after birth. A further aim of the study was to assess the association between severity of hypoxic-ischemic encephalopathy and altered thyroid hormone and TSH levels, and between mortality and FT4 levels in the arterial blood of newborns between 18 and 24 h of life. METHODS: A case-control study was carried out. The case group comprised 17 term newborns (Apgar score < or = 3 and < or = 5 at the first and fifth minutes; umbilical cord blood pH < or = 7.15) who required bag and mask ventilation for at least one minute immediately after birth. The control group consisted of 17 normal, term newborns (Apgar score > or = 8 and > or = 9 at the first and fifth minutes; umbilical cord blood pH > or = 7.2). Cord blood and arterial blood samples were collected immediately after birth and 18 to 24 h after birth, respectively, and were used in the blood gas analysis and to determine serum concentrations of T4, T3, FT4, rT3 and TSH by radioimmunoassay. All newborns were followed-up until hospital discharge or death. RESULTS: Gestational age, birthweight, sex, size for gestational age, mode of delivery and skin color (white and non-white) were similar for both groups. No differences were found in mean levels of cord blood TSH, T4, T3 and FT4 between the groups. In the samples collected 18 to 24 h after birth, mean levels of TSH, T4, T3 and FT4 were significantly lower in the asphyxiated group than in the control group. Mean concentrations of arterial TSH, T4 and T3 between 18 and 24 h of life were lower than concentrations found in the cord blood analysis in asphyxiated newborns, but not in controls. In addition, asphyxiated newborns with moderate/severe hypoxic-ischemic encephalopathy presented significantly lower mean levels of TSH, T4, T3 and FT4 than those of controls. None of the asphyxiated newborns with FT4 > or = 2.0 ng/dl died; 6 out of the 11 asphyxiated newborns with FT4 < 2.0 ng/dl died. CONCLUSIONS: Serum concentrations of TSH, T4, T3 and FT4 are lower in asphyxiated newborns than in normal newborns between 18 and 24 h of life; this suggests central hypothyroidism secondary to asphyxia. Asphyxiated newborns with moderate/severe hypoxic-ischemic encephalopathy present a greater involvement of the thyroid function and consequently a greater risk of death.

A randomized, double-masked, placebo-controlled trial of recombinant granulocyte colony-stimulating factor administration to preterm infants with the clinical diagnosis of early-onset sepsis.

OBJECTIVE: We performed a randomized, double-masked, parallel-groups, placebo-controlled trial of recombinant granulocyte colony-stimulating factor (rG-CSF) administration to 44 preterm neonates who had blood cultures obtained and antibiotics begun because of the clinical diagnosis of early-onset sepsis. Two primary outcome variables were tested 1) mortality and 2) development of nosocomial infections over the 2-week period after dosing. DESIGN AND METHODS: The treatment group (n = 22) received 10 microgram/kg/day of intravenous rG-CSF once daily for 3 days and the placebo group (n = 22) received the same volume of a visually indistinguishable vehicle. Mortality and culture-proven nosocomial infections were recorded. Immediately before the first, second, and third doses, and again 10 days after the first dose, serum concentrations were determined for tumor necrosis factor-alpha, interleukin 6, granulocyte-macrophage colony stimulating factor, and G-CSF, and blood leukocyte counts, absolute neutrophil counts, immature/total neutrophil ratios, platelet counts, and hemoglobin concentrations were measured. RESULTS: The treatment and placebo groups were of similar gestational age (29 +/- 3 vs 31 +/- 3 weeks) and birth weight (1376 +/- 491 vs 1404 +/- 508 g), and had similar Apgar scores and 24-hour Score for Neonatal Acute Physiology scores. The mortality rate was not different between treatment and placebo groups. However, the occurrence of a subsequent nosocomial infection was lower in the rG-CSF recipients (relative risk:.19; 95% confidence interval:.05-.78). rG-CSF treatment did not alter the serum concentrations of the cytokines measured (except for G-CSF). Serum G-CSF levels and blood neutrophil counts were higher in the treatment than in the placebo group 24 hours and 48 hours after dosing. CONCLUSIONS: Administration of 3 daily doses of rG-CSF (10 microgram/kg/day) to premature neonates with the clinical diagnosis of early-onset sepsis did not improve mortality but was associated with acquiring fewer nosocomial infections over the subsequent 2 weeks.

[Effect of perinatal asphyxia on thyroid hormones] / Efeitos da Asfixia Perinatal sobre os Hormônios Tireoidianos.

OBJECTIVE: To verify the effect of perinatal asphyxia on thyroid hormone levels in term newborn infants. METHODS: We carried out a case-control study with 17 term and asphyxiated (A) and 17 term and control (N) newborn infants at the Hospital de Clínicas de Porto Alegre. Patients were paired according to color of skin, sex, type of delivery, gestational age, and weight at birth. We collected umbilical cord plasma T4, T3, free T4, reverse T3, and TSH after 18 to 24 hours of life and from asphyxiated and control newborn infants. RESULTS: There were no differences in thyroid hormones of cord blood, with the exception of reverse T3, which was higher in A than in controls [median (25th-75th percentile): A= 2(1.4-2); N= 1.41 (1.13-1.92); P=0.037)]. Thyroid hormone levels were lower in A than in controls on samples collected within 18-24 hours after birth, except for reverse T3, which was similar in both groups [average -/+ SD: T4 A= 9.79 -/+ 2.59; N=14.68 -/+ 3.05; P<0.001; median T3 A= 40.83 (37.4-80.4); N= 164 (56.96-222.5); P=0.003; average -/+ SD: free T4 A=1.85 -/+ 0.92; N= 2.8 -/+ 0.74; P=0.004; median: reverse T3 A=1.54 (1.16-1.91); N=1.31(0.87-2); P=0.507; TSH A=9.1 (6.34-12.95); N=14.5(12.9-17.85); P=0.008]. CONCLUSIONS: Our data suggest that lower T4, free T4, and T3 levels are secondary to lower TSH levels in asphyxiated newborns; also, peripheral metabolism of T4 in asphyxiated infants can be altered due to low T3 and normal reverse T3 levels.

[The effect of recombinant human erythropoietin on the treatment of anemia of prematurity] / O efeito da eritropoetina humana recombinante no tratamento da anemia da prematuridade.

OBJECTIVE: To assess the efficacy of erythropoietin in the prevention and treatment of anemia of prematurity, correlating the use of this drug with weight gain, length, and head circumference and comparing two administration schemes of he same weekly dose: daily use and twice a week. METHODS: The study comprised 42 premature newborns with gestational age up to 33 weeks, birthweight up to 1550 g, and postnatal age between 10 and 35 days. The newborns were randomized into three groups: patients in group 1 received seven daily doses of 100 U/kg erythropoietin per week; patients in group 2 received two 350 U/kg erythropoietin doses per week; and patients in group 3 did not receive the drug. Hematologic measurements, blood transfusion requirements, and growth rates were followed during therapy. RESULTS: Cases and controls did not differ with respect to weight, length, head circumference, and total time of hospital stay. At the end of the study, no significant difference was observed in the platelet count measurement means, white blood cell count, and ferritin levels in the three groups. However, the final hematocrit and hemoglobin values of patients who did not receive erythropoietin were significantly lower than those of patients who received the drug. The absolute reticulocyte count mean was significantly higher in patients who received erythropoietin after two weeks of treatment when compared with those patients who did not receive the drug. Patients in group 1 e 2 received fewer excessive transfusions (2 or more) than patients in group 3. The administration of 700 U/kg/week erythropoietin significantly reduced the number of excessive blood transfusions. There is no significant difference in blood transfusion volume between patients who received erythropoietin on a daily basis and those who received the drug twice weekly. CONCLUSIONS: the use of erythropoietin did not influence weight gain and growth. The administration of 700 U/kg/week erythropoietin in premature infants with gestational age up to 33 weeks and birthweight up to 1550 g stimulates erythropoiesis and significantly reduces excessive blood transfusion requirements. Erythropoietin showed to be a safe and well tolerated medication, with no short-term side effects in the study population.

[Predictive value of SNAP and SNAP-PE for neonatal mortality] / Valor preditivo dos escores de SNAP e SNAP-PE na mortalidade neonatal.

OBJECTIVE: To evaluate the Score for Neonatal Acute Physiology and the Score for Neonatal Acute Physiology Perinatal Extension as neonatal mortality predictors in our neonatal intensive care unit, and to compare their results. METHODS: All newborn infants admitted to our neonatal intensive care unit from March 1997 through December 1998 were prospectively evaluated just at completion of 24 hours of life for SNAP and SNAP-PE. Exclusion criteria were: death or discharge from the neonatal intensive care unit in the first 24 hours of life, congenital malformations incompatible with life, and outborn infants. RESULTS: 553 newborn infants were included in the study and 54 died. The median SNAP and SNAP-PE values were higher in those who died. Infants were allocated to five different raising ranges of SNAP and SNAP-PE severity. SNAP: up to 6, 7-11, 12-15, 16-24, higher than 24 (mortality: 3%, 11%, 29%, 48%,75%, respectively). SNAP-PE: up to 11, 12-23, 24-32, 33-50, higher than 50 (mortality: 3%, 10%, 53%, 78%, 83%, respectively). The optimal cut off points based on ROC curve were 12 for SNAP, and 24 for SNAP-PE. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for death were figured out. SNAP 12: sensitivity 79.6%, specificity 71.7%, PPV 23.4%, NPV 97%. SNAP-PE 24: sensitivity 79.6%, specificity 80%, PPV 30%, NPV 97.3%. The area under the curve (Az) were 81.4% for SNAP, and 85.1% for SNAP-PE, both statistically significant. There were no statistical differences between the two areas under the curve. CONCLUSIONS: SNAP and SNAP-PE are excellent predictors of neonatal survival. Therefore, we recommend their use in Neonatal Intensive Care Units.

[Do newborn infants feel pain when submitted to gastric suctioning?] / Os recém-nascidos sentem dor quando submetidos à sondagem gástrica?

OBJECTIVES: Evaluate physiological and behavioral parameters to verify if newborns feel pain when submitted to gastric suctioning. METHODS: 50 healthy newborns over 33 weeks gestational age, weighing more than 1999g, were submitted to gastric suctioning, randomly selected, and divided into two groups: Friction/Lancing and Lancing/Friction. The newborns were assessed through the Neonatal Infant Pain Scale (NIPS) (0-7, pain>3) by two independent observers in three different moments: one minute before, during, and one minute after gastric suctioning, heel lancing and foot friction, with simultaneous monitoring of heart rate, respiratory frequency, and hemoglobin oxygen saturation. RESULTS: The respiratory frequency only decreased during gastric suctioning (P=0.004). The heart rate was lower during gastric suctioning (P<0.0001), during the heel lacing procedure in the Friction/Lancing group (P=0.01), and during friction in the Friction/Lancing group (P=0.022). The hemoglobin oxygen saturation suffered no alterations during the three procedures. The results obtained through NIPS revealed that both groups felt pain during gastric suctioning and heel lancing, and did not feel pain during friction (P<0.0001). CONCLUSION: During the gastric suctioning procedure, newborns responded as if it were a painful stimulus. Physiological alterations were neither specific nor sensitive to pain assessment in newborn infants.

[Hypoxic-ischemic syndrome] / Síndrome hipóxico-isquêmica.

OBJECTIVE: To review the literature on the hypoxic-ischemic syndrome, emphasizing its physiopathology, clinical manifestations, and treatment. SOURCES: Electronic search in the Medline and LILACS databases, with selection of the most relevant articles. SUMMARY OF THE FINDINGS: The hypoxic-ischemic syndrome is a multisystem disease with generalized manifestations. The physiopathology is based on hypoxic-ischemic brain injury and reperfusion with cellular injury caused by failure of ATP production secondary to ischemia, and overproduction of oxidative substances caused by reperfusion. Neurological, cardiovascular, respiratory, metabolic, gastrointestinal, renal, and hematological manifestations are frequent. Multisystem clinical management is complex; the neuroprotective approach is still experimental; and the prognosis is not good for those patients with severe hypoxic-ischemic encephalopathy. CONCLUSIONS: The management of the hypoxic-ischemic syndrome is a great challenge to pediatricians., since treatment requires multisystem intervention.

[Assessing the efficacy of the recombinant human granulocyte colony-stimulating factor "rhG-CSF" in the treatment of early neonatal sepsis in premature neonates] / Avaliação da eficácia do fator estimulador recombinante humano de colônias de granulócitos "rhG-CSF" no tratamento da sepse de início precoce, em recém-nascidos prematuros.

OBJECTIVE: To evaluate the efficacy of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) in the treatment of early-onset neonatal sepsis among premature infants.MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled trial was performed among forty-four preterm neonates who had "clinical diagnosis" of early-onset sepsis. The treatment group (n=22) received 10 micro g/kg/d of rhG-CSF, IV once daily for three consecutive days, and the placebo group (n=22) received the same volume of a visually-indistinguishable vehicle. Prior to the first dose, and prior to the second and third doses, and again 10 days after the first dose, we measured tumor necrosis factor-a, interleukin-6, granulocyte-macrophagocyte colony-stimulating factor, G-CSF, leukocyte count, absolute neutrophil count, immature/total neutrophil ratio, platelet count, and hemoglobin concentration. A bone marrow aspiration was performed seven days after the first dose, and both the neutrophil storage pool (NSP) percent and the NSP/NPP (neutrophil proliferative pool) ratios were tabulated.RESULTS: The treatment and placebo groups were of similar gestational age (29-/+ 3 vs 31-/+ 3 weeks) and birth weight (1376 -/+ 491 vs 1404 -/+ 508 grams). They had similar Apgar scores and 24 hour SNAP scores. No deaths occurred during the first week of life among the treatment group while three deaths occurred in the placebo group. RhG-CSF treatment did not alter the serum concentrations of the cytokines measured (except for G-CSF). Serum G-CSF levels, blood leukocyte counts, absolute neutrophil counts, NSP percentages, and NSP/NPP ratios were higher in the treatment group 24 hours and 72 hours after dosing. The occurrence of a subsequent infection over the two week period following dosing was significantly lower in the treatment group (n=2) than in the placebo group (n=9; p<0.02, RR 0.19 [0.05-0.78]). The overall mortality rate during the entire hospitalization was not different between treatment and placebo groups.CONCLUSIONS: Administration of rhG-CSF to premature neonates with the clinical diagnosis of early-onset sepsis was associated with lower incidence of nosocomial infection over the ensuing three weeks period, but it did not change the overall mortality rate.

Evaluation of interleukin-6, tumour necrosis factor-alpha and interleukin-1beta for early diagnosis of neonatal sepsis.

The objective of this study was to assess the contribution of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) to an early diagnosis of early-onset neonatal sepsis. A cohort of 117 newborn infants delivered during a 1-y period had IL-6, TNF-alpha and IL-1beta, blood and cerebrospinal fluid (CSF) cultures, leucocyte and platelet count collected on the initial evaluation of possible early-onset sepsis. They were divided into four groups: I, positive blood and/or CSF cultures; II, probably infected with clinical sepsis but negative cultures; III, same as group II but mother received antibiotic antepartum; and IV, newborn infants that did not receive any antibiotic therapy. There were no differences among the four groups with respect to mean gestational ages and birthweights, median Apgar scores, type of delivery, or number of newborn infants with leucocyte count <5000 mm(-3) or >25000 mm(-3), platelet count <100000 mm(-3), immature/total neutrophil ratio >0.2, absolute neutrophil count <1000mm(-3) and median IL-1beta levels. Median IL-6 and TNF-alpha levels were significantly higher in groups with patients with a diagnosis of clinical sepsis than in controls. The optimal cut-off point was 32 pg ml(-1) for IL-6 and 12 pg ml(-1) for TNF-alpha. The combination of both provided a sensitivity of 98.5%. In conclusion, the combination of IL-6 and TNF-alpha is a highly sensitive marker of sepsis in the immediate postnatal period.