Ronald L. Poland

Incidence, presenting features, risk factors and significance of late onset septicemia in very low birth weight infants

BACKGROUND Septicemia is a major antecedent of morbidity and mortality in very low birth weight (501- to 1500-g) infants. Our purpose was to determine prospectively the incidence, clinical presentation, laboratory features, risk factors, morbidity and mortality associated with late onset septicemia in infants 501 to 1500 g. METHODS Clinical data were prospectively collected for 2416 infants enrolled in a multicenter trial to determine the efficacy of intravenous immunoglobulin in preventing nosocomial infections. Septicemia was confirmed by positive blood culture in 395 symptomatic infants. Multivariate analyses of factors associated with septicemia were performed. RESULTS Sixteen percent of VLBW infants developed septicemia at a median age of 17 days. Factors associated with septicemia by logistic regression included male gender, lower gestational age and birth weight and decreased baseline serum IgG concentrations. Increasing apnea (55%), feeding intolerance, abdominal distension or guaiac-positive stools (43%), increased respiratory support (29%), lethargy and hypotonia (23%) were the dominant presenting features of septicemia. An abnormal white blood cell count (46%), unexplained metabolic acidosis (11%) and hyperglycemia (10%) were the most common laboratory indicators. Septicemic infants, compared with nonsepticemic infants, had significantly increased mortality (21% vs. 9%), longer hospital stay (98 vs. 58 days) and more serious morbidity, including severe intraventricular hemorrhage, bronchopulmonary dysplasia and increased ventilator days (P < 0.001). CONCLUSIONS Late onset septicemia is common in very low birth weight infants, and the rate is inversely proportional to gestational age and birth weight. Septicemia is more common in males and those with low initial serum IgG values. A set of clinical signs (apnea, bradycardia, etc.) and laboratory values (leukocytosis, immature white blood cells and neutropenia) increase the probability of late onset sepsis, but they have poor positive predictive value.

A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants

BACKGROUND Nosocomial infections are a major cause of morbidity and mortality in premature infants. As a rule, their low serum gamma globulin levels at birth subsequently decline to hypogammaglobulinemic values; hence, prophylactic administration of intravenous immune globulin may reduce the rate of hospital-acquired infections. METHODS In this prospective, multicenter, two-phase controlled trial, 2416 infants were stratified according to birth weight (501 to 1000 g and 1001 to 1500 g) and randomly assigned to an intravenous immune globulin group (n = 1204) or a control group (n = 1212). Control infants were given placebo infusions during phase 1 of the study (n = 623) but were not given any infusions during phase 2 (n = 589). Infants weighing 501 to 1000 g at birth were given 900 mg of immune globulin per kilogram of body weight, and infants weighing 1001 to 1500 g at birth were given a dose of 700 mg per kilogram. The immune globulin infusions were repeated every 14 days until the infants weighed 1800 g, were transferred to another center, died, or were sent home from the hospital. RESULTS Nosocomial infections of the blood, meninges, or urinary tract occurred in 439 of the 2416 infants (18.2 percent): 208 (17.3 percent) in the immune globulin group and 231 (19.1 percent) in the control group (relative risk, 0.91; 95 percent confidence interval, 0.77 to 1.08). Septicemia occurred in 15.5 percent of the immune globulin recipients and 17.2 percent of the controls. During phase 1 the rate of nosocomial infections was 13.4 percent in the immune globulin group and 17.8 percent in the control group; the respective rates during phase 2 were 21.0 percent and 20.4 percent. The predominant organisms included gram-positive cocci (53.0 percent), gram-negative bacilli (22.4 percent), and candida species (16.0 percent). Adverse reactions were rarely observed during the infusions. Immune globulin therapy had no effect on respiratory distress syndrome, bronchopulmonary dysplasia, intracranial hemorrhage, the duration of hospitalization, or mortality. The incidence of necrotizing enterocolitis was 12.0 percent in the immune globulin group and 9.5 percent in the control group. CONCLUSIONS Prophylactic use of intravenous immune globulin failed to reduce the incidence of hospital-acquired infections in very-low-birth-weight infants.

Sonographic classification of intracranial hemorrhage. A prognostic indicator of mortality, morbidity, and short-term neurologic outcome

Sixty-two neonates diagnosed to have periventricular-intraventricular hemorrhage were classified by sonographic findings as follows: mild, confined to the subependymal region or accompanied by a small amount of blood in the normal-sized lateral ventricle (10); moderate, intermediate amount of blood in the enlarged lateral ventricle (26); and severe, hemorrhage filling the entire ventricle forming a cast (12) or intraventricular hemorrhage with an intracerebral extension (14). Twenty-six of 35 surviving neonates had posthemorrhagic hydrocephalus, and 11 infants required shunt insertion. The survival rate of neonates with periventricular-intraventricular hemorrhage and the incidence of posthemorrhagic hydrocephalus correlated with the severity of the hemorrhage (P less than 0.05). The highest mortality rate was seen in the group with ventricular casts. All surviving neonates with casts developed hydrocephalus. All surviving neonates with intracerebral hemorrhage developed porencephaly. The severity of the hemorrhage correlated with short-term neurologic outcome (P less than 0.05), the group most severely affected being the one with intracerebral extension of hemorrhage. The severity of the hemorrhage also correlated with abnormal ventricular size by sonography on follow-up (P less than 0.05). However, posthemorrhagic hydrocephalus and abnormal ventricular size on follow-up did not correlate with neurologic outcome in the moderate and severe hemorrhage groups.

Sodium Bicarbonate: Basically Useless Therapy

Common clinical practices often are unsupported by experimental evidence. One example is the administration of sodium bicarbonate to neonates. Despite a long history of widespread use, objective evidence that administration of sodium bicarbonate improves outcomes for patients in cardiopulmonary arrest or with metabolic acidosis is lacking. Indeed, there is evidence that this therapy is detrimental. This review examines the history of sodium bicarbonate use in neonatology and the evidence that refutes the clinical practice of administering sodium bicarbonate during cardiopulmonary resuscitation or to treat metabolic acidosis in the NICU.

The effect of vitamin E prophylaxis on the incidence and severity of bronchopulmonary dysplasia

Forty-four infants (21 treated and 23 control subjects) ventilated for hyaline membrane disease were enrolled in a controlled trial of vitamin E (Roche E injectable) supplementation to assess the effects of the vitamin on the development of bronchopulmonary dysplasia. The two groups did not differ significantly in gestational age, birth weight, Apgar scores, the amount of oxygen received, the level of positive pressure applied per ventilator, or the time of exposure to oxygen and positive pressure. Peak pressures exceeding 40 cm H 2 O were uncommon (

Antenatal phenobarbital for the prevention of neonatal intracerebral hemorrhage

Forty-six pregnant women less than 35 weeks of gestation were enrolled in a prospective randomized controlled study evaluating the effects of antenatal phenobarbital on neonatal intracerebral hemorrhage. The women were randomly assigned to control (n = 22) or treatment (n = 24) groups; the treatment group received 500 mg of phenobarbital intravenously. The time interval between the dose of phenobarbital and delivery was 5.5 +/- 4.8 hours (mean +/- SD). The infants in the control group (n = 23) and those in the phenobarbital-treated group (n = 25) were comparable regarding birth weight, gestational age, and other obstetric and neonatal risk factors associated with intracerebral hemorrhage. The incidence of intracerebral hemorrhage was 56.5% (13 of 23 infants) in the control group and 32% (eight of 25 infants) in the phenobarbital-treated group (p = 0.08). Moderate or severe hemorrhage was diagnosed in six of 13 control infants and in none of the phenobarbital-treated infants (p less than 0.01). The mortality rate was significantly lower in the phenobarbital-treated group (two of 25 infants) than in the control group (eight of 23 infants; p less than 0.05). Our study suggests that antenatal phenobarbital administration results in a decrease in mortality and in the severity of intracerebral hemorrhage in the preterm neonate.

High milk lipase activity associated with breast milk jaundice.

Summary: Human milk samples that inhibit bilirubin-UDP-glucuronyl transferase (UDPGT) activity in vitro have been associated with prolonged unconjugated hyperbilirubinemia in newborn infants. We measured the concentrations of nonesterified fatty acids (total and individual fatty acids), total fat and protein, and lipase activities (with and without bile salt stimulation) in milk samples from two groups of women. Women whose infants had prolonged unconjugated hyperbilirubinemia and whose milk inhibited the activity of UDPGT were in the first group (N = 9). Volunteers with healthy infants acted as controls.Inhibitory milk contained significantly more nonester?fied fatty acids (total, palmitic, and oleic) than did controls. Fat and protein concentrations and bile salt-stimulated lipase activities were similar in the two groups. Unstimulated lipase activity was higher in the inhibitory milks (11.9 ± 0.8 mM±min-1±ml-1) than in the controls (6.0 ± 0.2 mM±min-1±ml-1) (P ≤0.01). The specific activity (mM±min-1±mg protein-1) of unstimulated lipase was also significantly higher in the inhibitory milks (P ≤0.0001).The high nonesterified fatty acid levels in inhibitory milks is accounted for by the elevated unstimulated lipase activities. How these circumstances lead to jaundice in the infants remains to be shown.Speculation: The strong association between high unstimulated lipase activity in human milk and the syndrome of breast milk jaundice leads us to conclude that fat digestion and absorption may have an important efffect on the metabolism of bilirubin in newborn infants. Further studv of the influence of the digestive Drocess on the absorption aid further metabolism of dietaiy lipid ih neonates may help to illuminate the relationship between lipid metabolism and neonatal hyperbilirubinemia.

The displacement of bilirubin from albumin byfurosemide

Since furosemide, a sulfonamide diuretic, has been recommended for use in the newborn infant, a study was made of its effect on the bilirubin-binding capacity of albumin. Furosemide was compared to sulfisoxazole, a known displacer of bilirubin, by means of three methods. First, aliquots of whole blood from 20 icteric infants were diluted in phosphate buffer along with expected clinical concentrations of furosemide and sulfisoxazole. The red cells and globulins were then isolated and bilirubin concentrations were measured in these two fractions. The addition of Furosemide resulted in the displacement of bilirubin from albumin to red cells and globulins. Mole for mole, furosemide displaced bilirubin about as well as sulfisoxazole. Second, the hydroxybenzeneazobenzoic acid dye binding test of Porter and twaters was performed using the sera of eight jaundiced newborn infants. The mean dye binding capacity of the sera was significantly reduced with the addition of furosemide to a final concentration of 2 mug/ml. Third, the administration of furosemide (5 mg/kg) or sulfisoxazole (50 mg/kg) to adult Gunn rats resulted in a significant fall in mean serum bilirubin concentration compared to saline controls. Furosemide, like sulfisoxazole, is a potent displacer of bilirubin and should be used with caution in jaundiced infants.

Normal values for ventricular size as determined by real time sonographic techniques

Seventy-three real time sonographic scans were performed through the anterior fontanelle of 67 infants between 28 and 48 weeks post-conception who had no evidence of intracranial disease. Several anatomical measurements were plotted against independent variables such as post-conception age, weight and head circumference at the time of the examination. All of the measurements increased as age, weight and head circumference increased. Ratios formed by dividing transventricular diameters by transcalvarial diameters at the two levels in the coronal plane and by dividing occipital mantle thickness by frontal mantle thickness in the parasagittal planes remained stable as all of the independent variables increased. In 88% of cases the occipital mantle could not be measured since the occipital horns of the lateral ventricles could not be identified. Since dilation of the ventricular system starts in the occipital horns of the lateral ventricles, non-visualization of this area is an important negative finding.

EFFECT OF VITAMIN E DEFICIENCY ON PULMONARY OXYGEN TOXICITY

Adult female white mice were divided into two groups. One was fed a diet deficient in vitamin E (E-) and the other (E+) was fed the same mixture with D-a-tocopherol added (100 mg/kg chow). The following were evaluated: serum tocopherol concentrations, lung weight and sodium content, and the survival time of the animals in oxygen. Mean serum tocopherol concentrations were 2.1 ug/ml and 14.5 ug/ml (p<.005). Lung wet weight, sodium content and water content increased with time in 65% and 100% oxygen. E- mice had more sodium retention/gin lung than E+ mice (p<.05). Survival:Electron microscope studies of lungs that were fixed with glutaraldehyde at 20 cmH2O pressure showed vitamin E related differences. Oxygen (65% x 3-6 days) caused disruption of pulmonary capillary endothelial junctions and of the structure of the mitochondrial cristae in E- mice but not in E+ mice. Edema and fibrin deposition were greater in the E- group. These changes were not observed in animals kept in room air.These results indicate that vitamin E deficiency enhances the toxic effects of oxygen in mice.