Gary E. Stahl

Pepsin, a Marker of Gastric Contents, Is Increased in Tracheal Aspirates From Preterm Infants Who Develop Bronchopulmonary Dysplasia

OBJECTIVE. The objective of this study was to study the association between pepsin in tracheal aspirate samples and the development of bronchopulmonary dysplasia in preterm infants. METHODS. Serial tracheal aspirate samples were collected during the first 28 days from mechanically ventilated preterm neonates. Bronchopulmonary dysplasia was defined as the need for supplemental oxygen at 36 weeks’ postmenstrual age. An enzymatic assay with a fluorescent substrate was used to detect pepsin. Total protein was measured by the Bradford assay to correct for the dilution during lavage. Immunohistochemistry using antibody against human pepsinogen was performed in 10 lung tissue samples from preterm infants. RESULTS. A total of 256 tracheal aspirate samples were collected from 59 preterm neonates. Pepsin was detected in 234 (91.4%) of 256 of the tracheal aspirate samples. Twelve infants had no bronchopulmonary dysplasia, 31 infants developed bronchopulmonary dysplasia, and 16 infants died before 36 weeks’ postmenstrual age. The mean pepsin concentration was significantly lower in infants with no bronchopulmonary dysplasia compared with those who developed bronchopulmonary dysplasia or developed bronchopulmonary dysplasia/died before 36 weeks’ postmenstrual age. Moreover, the mean pepsin level was significantly higher in infants with severe bronchopulmonary dysplasia compared with moderate bronchopulmonary dysplasia. The mean pepsin level in tracheal aspirate samples from the first 7 days was also lower in infants with no bronchopulmonary dysplasia compared with those who developed bronchopulmonary dysplasia or developed bronchopulmonary dysplasia/died before 36 weeks’ postmenstrual age. Pepsinogen was not localized in the lung tissues by immunohistochemistry. CONCLUSION. The concentration of pepsin was increased in the tracheal aspirate of preterm infants who developed bronchopulmonary dysplasia or died before 36 weeks’ postmenstrual age. Recovery of pepsin in tracheal aspirate samples is secondary to gastric aspiration, not by hematogenous spread or local synthesis in the lungs. Chronic aspiration of gastric contents may contribute in the pathogenesis of bronchopulmonary dysplasia.

Effect of heparin dose and infusion rate on lipid clearance and bilirubin binding in premature infants receiving intravenous fat emulsions

The effect of heparin dose and infusion rate on plasma lipids, lipases, and unbound bilirubin was investigated in 22 premature infants with physiologic jaundice. Infants were randomly assigned to receive low or high intravenous doses (24 vs 137.3 U/day) of heparin. Each patient then received 2 g/kg/day of 10% Intralipid on 2 successive days: one day during a 15-hour period and the other day over 24 hours, with the order assigned randomly. The results demonstrate a significantly greater change in serum-free fatty acids in infants receiving the high heparin dose during the 15-hour lipid infusion period. Lipoprotein lipase activity rose more with the high heparin dose and equally at either infusion rate. We conclude that lipid infusions of 2 g/kg/day with low heparin dosage infused over 24 hours resulted in less elevation in serum-free fatty acids. There were no adverse effects on unbound bilirubin at either infusion rate or heparin dosage.

Total parenteral nutrition with intralipid in premature infants receiving TPN with heparin: effect on plasma lipolytic enzymes, lipids, and glucose.

Plasma lipolytic activity (lipoprotein lipase and hepatic lipase), free fatty acids (FFA), triglycerides, cholesterol, and glucose levels were measured in 21 premature infants [gestational age 26-37 weeks (mean +/- SEM 30.4 +/- 0.63 weeks), aged 1-8 days (mean +/- SEM 3.00 +/- 0.35 days)]. All infants were maintained on total parenteral nutrition with heparin (1 U/ml) and were given Intralipid, 1, 2, and 3 g/kg/day, over 15 h on days 1, 2, and 3, respectively. Blood samples were drawn before and at the end of Intralipid administration. Baseline plasma lipolytic activity, before the start of lipid infusion, was 1.54 +/- 0.24 U/ml (1 U = 1 mumol [3H]oleic acid released from tri[3H]olein/h). Lipolytic activity increased after lipid infusion to 4.04 +/- 0.96, 4.32 +/- 0.63, and 6.09 +/- 1.00 U/ml on days 1, 2, and 3 of the study. Hepatic lipase amounted to 38-47% of total lipolytic activity. During the 3 days of lipid infusion, there were dose-dependent increases in plasma FFA, triglyceride, and cholesterol. Whereas FFA and triglyceride concentrations returned to prelipid infusion levels 9 h after stopping the infusion of Intralipid, 1, 2, or 3 g/kg, there was a cumulative increase in plasma cholesterol and glucose concentrations. The close correlation between FFA concentrations and plasma lipolytic activity (r = 0.655, p less than 0.001) suggests considerable intravascular lipolysis. The positive correlation between plasma FFA and triglycerides (r = 0.632, p less than 0.001) and FFA and cholesterol (r = 0.582, p less than 0.001) indicate, however, that intravascular lipolysis does not prevent the lipemia associated with Intralipid infusion to low birth weight infants.(ABSTRACT TRUNCATED AT 250 WORDS)

The Effect of 15-Hour Fat Infusions of Varying Dosage on Bilirubin Binding to Albumin

Intravenous fat emulsions (1, 2, and 3 g/kg) were administered over 15 hr to 20 appropriate for gestational age premature infants with physiologic hyperbilirubinemia to determine the effect of fat infusions on the serum free fatty acid:albumin molar ratio (F/A) and on unbound bilirubin. Significant increases (p less than 0.05) in F/A occurred with each increase in lipid dose in infants less than 30 wk gestation, but not in infants greater than or equal to 30 wk gestation. There was a direct linear correlation (r = 0.65, p less than 0.001) between F/A ratio and unbound bilirubin (estimated fluorometrically by the ratio of albumin-bound bilirubin/reserve bilirubin binding capacity, B/R). The largest increases in unbound bilirubin (albumin-bound bilirubin/reserve bilirubin binding capacity) were seen in infants with F/A greater than 4.0. The gestational age of infants with F/A greater than 4.0 was significantly less (p less than 0.01) than infants with F/A less than 4.0 (28.7 +/- 0.47 vs. 31.1 +/- 0.40 wk, mean +/- SEM). In 10/58 infusions there was a fall in unbound bilirubin, unrelated to birthweight, gestational age, postnatal age, however, during these infusions the end-infusion F/A was greater than or equal to 3.0. We conclude that 1 g/kg of lipid emulsion infused over a 15-hr period has minimal risk of decreasing bilirubin binding in premature infants less than 30 wk gestation. As doses of 2 or 3 g/kg are used, these infants may be at risk of decreased bilirubin binding, due to elevations in the F/A ratio. Monitoring of the F/A ratio may identify infants at risk for decreased bilirubin binding during lipid infusion and provide guidelines for determining the appropriate lipid dose.

Long-term assessment of growth, nutritional status, and gastrointestinal function in survivors of necrotizing enterocolitis

The long-term effect of necrotizing enterocolitis on growth, nutritional status, and gastrointestinal function was assessed in premature infants at the age of 1 year. Of the 22 of 40 infants who developed NEC, 18 were given medical treatment and four required surgical treatment consisting of intestinal resection of less than one fourth of the small bowel. Eighteen infants who did not develop NEC served as controls. At 1 year follow-up, NEC survivors and controls had normal and comparable anthropometric measurements, biochemical values (serum iron, albumin, prealbumin, retinol binding protein, liver function studies) and gastrointestinal tract function (vitamin E absorption, fasting serum bile acids concentration, lactose breath test). This study demonstrates that, in the absence of short bowel syndrome, there is no detectable long-term effect on growth, nutritional status, and gastrointestinal tract function in premature infants who had NEC in the newborn period.

Single-dose treatment of uncomplicated urinary tract infections in children

Thirty-six girls, aged two to 17 years, with culture-proven, acute, uncomplicated lower urinary tract infections and without signs or symptoms of upper urinary tract infection, were randomized to receive either single-dose amoxicillin or conventional therapy for ten days. Twenty-six patients completed the study, ten in the single-dose group and 16 in the conventional therapy group. The patients treated with single-dose therapy had cure rates (70% vs 75%), relapse rates (30% vs 25%), and reinfection rates (0% vs 12%) comparable to those of conventionally treated patients. A significant difference in the induction of resistant organisms was seen between treatment groups (P less than .05). All single-dose relapses were due to failure to clear a sensitive organism from the urinary tract. All relapses on conventional therapy resulted from an initially sensitive organism becoming resistant to amoxicillin during treatment. Single-dose antibiotic therapy of uncomplicated urinary tract infections in children is effective in patients with culture-proven infections selected by clinical criteria, and appears to be safe when combined with conscientious long-term follow up and radiographic evaluation. Single-dose therapy offers the advantage of selecting significantly fewer resistant organisms from the gut flora than do conventional antibiotic regimens.

Randomized trial of prophylactic phototherapy in the infant with very low birth weight

Twenty-two preterm infants (birth weight 850 +/- 220 gm) were randomly assigned to receive phototherapy either soon after birth or after the serum bilirubin concentration reached 5 mg/dl. Infants receiving prophylactic phototherapy were placed under lights at a significantly earlier age and lower serum bilirubin concentration than infants in the routine group (P less than 0.001). There was no significant difference between groups in peak serum bilirubin concentration, age at which it peaked, rate of rise in serum bilirubin concentration, or serum bilirubin concentration at any time during the study. Infants assigned to the prophylactic phototherapy group were under lights for a significantly longer time than those in the routine group (P less than 0.05). There was a significant rise in both configurational and structural photo-isomers (P less than 0.005) independent of serum bilirubin concentration after phototherapy in all patients. These data suggest that the clinical course of hyperbilirubinemia is not altered in infants with very low birth weight receiving prophylactic phototherapy compared with infants with phototherapy begun at a bilirubin concentration of 5 mg/dl.

Comparison of nonabsorbable markers Poly R-478 and (14C)PEG-4,000 for use in developmental absorption studies

To determine the utility of Poly R-478, a stable, polymeric dye (MW, 40,000), as a nonabsorbable marker for studies in the developing small intestine, it was validated by comparison to carbon 14-labeled polyethylene glycol, MW 4,000 [( 14C]PEG-4,000) in rats from 14 to 40 days of age. The recovery and quantification of Poly R-478 from biological samples is simple and rapid compared to other nonradioactive nonabsorbable markers. In 40-day-old rats simultaneously given Poly R-478 and [14C]PEG, total recoveries were similar, the percentages of the Poly R-478 dose and the [14C]PEG dose recovered per segment were identical, and taurocholate absorption rates calculated using each marker were comparable. Recovery of Poly R-478 from flushed intestinal segments, determined by a one-step extraction, was equivalent to that of [14C]PEG in 40-day-old rats (96.5 +/- 3.7% versus 102.7 +/- 10.1%; NS) but was superior to that of [14C]PEG in 21-day-old rats (98.0 +/- 6.2% versus 63.4 +/- 5.5%; p less than 0.001) and 14-day-old rats (97.8 +/- 6.7% versus 56.7 +/- 12.6%; p less than 0.001). Within each age group, the distribution of Poly R-478 within the intestine was similar to that of [14C]PEG. In addition, total taurocholate absorption in the presence of Poly R-478 was comparable to that in the presence of [14C]PEG. Complete recovery of Poly R-478 from a suspension of liver particles and from mixtures with two commercial infant formulas was demonstrated in vitro, suggesting that Poly R-478 may be used when foods are present in the intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidural analgesia and neonatal fever.

To the Editor. We read with interest the report of Lieberman et al1 regarding the relationship of the duration of epidural analgesia and fever in labor. We have had a long-held hypothesis regarding this relationship based on both the study of Fusi et al2 in 1989 and a retrospective study we performed and presented as a poster at the Society for Pediatric Research in 1990.3 Our prior study closely agrees with the conclusions in the Lieberman study. We analyzed computerized data on all 1909 infants admitted to the special care nurseries for a 30-month period, delivered by our obstetrical service with 60% epidural use. Fever in labor was found in 32% of the mothers with epidurals and in 12.5% of the mothers not given epidurals (χ2 94.11, P < .00001). Mothers with epidurals who had fever were given antibiotics more often ( P < .05), and term infants born to mothers with epidural and fever received significantly more lab tests and antibiotics ( P < .001) without any increase in culture-proven sepsis. Also, the length of stay for these latter infants averaged 6.7 days, compared with 3.0 days for children born to mothers who remained afebrile after epidural. Because our standard practice was to admit all infants of mothers with fever to the special care nurseries, the incidence of fever in the 8400 live births (all levels of gravidarity) was calculated as 5.7% with an incidence of approximately 2.5% in those without epidurals and 7.5% of those with epidural analgesia.3 These numbers, although less dramatic than the 1% and 14.5% found by Lieberman et al1 in their population of 1657 primigravidas, confirm the strong correlation of fever and epidural analgesia. Lieberman et al1 also concluded that there were more sepsis evaluations and antibiotic use in …

The effect of comprehensive infection control measures on the rate of late-onset bloodstream infections in very low-birth-weight infants.

Late-onset bloodstream infection (LOBI) is a significant problem in very low-birth-weight (VLBW) infants and can lead to increased mortality and morbidity. The incidence of LOBI in VLBW infants in our unit was >35% before 2004, much higher than 20% reported in other studies. A comprehensive infection control measure was introduced in our unit in 2005. Here we report the effects of comprehensive infection control measures on the rate of LOBI in VLBW infants. Infants in the preintervention group (born 2001 to 2004) were compared with the intervention group (born 2005 to 2008) for baseline demographics, risk factors for infection, and the rate of LOBI. LOBI was defined as a positive blood and/or cerebrospinal fluid culture after 3 days of life. Three hundred thirty-four VLBW infants were admitted to our unit during the preintervention period and 303 during the intervention period. There was no significant difference in baseline demographics and risk factors for LOBI between the two groups. The incidence of LOBI was significantly reduced from 38% before intervention to 23% after intervention ( P < 0.001). Comprehensive infection control measures significantly reduced the rate of LOBI in VLBW infants.