Fluconazole prophylaxis in extremely low birth weight infants: association with cholestasis.

BACKGROUND: Extremely low birth weight (ELBW) infants are at increased risk for invasive candidiasis and associated morbidity and mortality. The use of fluconazole prophylaxis in this population has raised a benefit versus risk concern among clinicians. OBJECTIVES: To evaluate the effectiveness and safety of fluconazole prophylaxis in ELBW infants. STUDY DESIGN: ELBW infants (BW

Work of breathing using high-flow nasal cannula in preterm infants.

OBJECTIVE: To compare the work of breathing (WOB) in premature neonates supported with high-flow nasal cannula (HFNC) and nasal continuous positive airway pressure (NCPAP). STUDY DESIGN: Eighteen preterm neonates <2.0 kg on HFNC or NCPAP support were studied in a random order. A ventilator was used to deliver 6 cm H2O of NCPAP with nasal prongs. High-flow nasal cannula delivered with Vapotherm (VAPO) at 3, 4 and 5 l/min was used. Tidal ventilation was obtained using respiratory inductance plethysmography calibrated with face-mask pneumotachography. An esophageal balloon estimated pleural pressure from which changes in end distending pressure were calculated. Inspiratory, elastic and resistive WOB and respiratory parameters were calculated. RESULTS: No differences were found in the WOB for all settings. Changes in end distending pressure did not vary significantly over all device settings except VAPO at 5 l/min. CONCLUSION: In these preterm infants with mild respiratory illness, HFNC provided support comparable to NCPAP.

Impaired sensitivity of a single early leukocyte count in screening for neonatal sepsis.

The common clinical practice of using a single, early white blood cell (WBC) count to screen for early onset neonatal sepsis was investigated in a population of 61 newborn infants with culture proven sepsis in the first 3 days of life. Thirteen patients (21%) had a falsely normal WBC screening test. The patients with true positive and falsely normal WBC counts did not differ by risk factors for sepsis, birth weight, age, outcome or severity of disease. However, there was a significant delay between the screening test and the positive blood culture in the patients with false normal WBC counts and not in the patients with positive abnormal WBC counts (14.9 +/- 5.9 hours vs. 2.8 +/- 1.4 hr, mean +/- SE, P less than 0.001). A WBC count obtained soon after birth as currently utilized may not adequately screen for early onset neonatal sepsis.

Predischarge monitoring of preterm infants.

The objectives of this study were: 1) to perform documented event-monitoring (DEM) for apnea (A, > or = 20 s) and bradycardia (B, < 80 beats per min for > or = 5 s) in premature infants prior to discharge, and 2) to examine the accuracy of nursing documentation (ND) of A and B. Forty-four stable preterm infants, with mean weights and gestational ages at birth (+/- SD) of 1,543 (+/- 365) g, and 30 (+/- 2) weeks, respectively, were studied using DEM for 9 (+/- 2) days prior to discharge. Differences in DEM and ND were analyzed by the z-test for proportions. There were 561 true events recorded by DEM: 56 were As and 505 were Bs. ND revealed 296 events, 190 As and 106 Bs. Of the 56 true As on DEM, only 21 (38%) were correctly reported by ND (P < 0.001, 95% confidence interval (CI) 0.44-0.81). Of the 505 true Bs on DEM, 153 (30%) were correctly reported by ND (P < 0.001, CI 0.63-0.76). When ND was compared with DEM, 174 (59%) of NDs were true events. Of the 106 As on ND, only 21 (20%) were true As on DEM (P < 0.001, CI 0.58-1). Of the 190 Bs on ND, 153 (80%) were true Bs on DEM (P < 0.001, CI 0.13-0.26). ND did not detect 6 of the 33 infants who had significant events on DEM, while 4 of the 11 who had events reported on ND did not have any on DEM. Thus, 10 infants were misclassified by ND (P < 0.01, CI 0.1-0.36). These results indicate that, compared to DEM, ND not only identified significantly fewer true As and Bs, but also misclassified a significant number of infants. We conclude that DEM performed prior to discharge for preterm infants at risk for apnea and bradycardia provides more objective and accurate information than ND.

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.

Intravenous administration of lipid emulsions to premature infants.

This article describes the mechanisms responsible for hydrolysis and clearance of triglyceride from the circulation and focuses on the factors that affect lipid clearance in the newborn infant. The potential beneficial and adverse effects of IV lipid administration to premature infants are reviewed in detail. Several practical considerations for IV lipid administration are also discussed.

Congenital right diaphragmatic hernia. A case report and review of the literature.

Congenital right diaphragmatic hernia can present a difficult diagnostic problem. An illustrative case is reviewed in which the diagnosis was not considered during the initial hospitalization because chest radiographs were interpreted as showing an atelectatic and pneumonic process. Once suspected, the diagnosis was made by fluoroscopy, which showed an immobile right hemidiaphragm, and by liver scan, which demonstrated herniation of the liver into the right thorax. The tendency of congenital right diaphragmatic hernias to present after the neonatal period and to mimic pulmonary parenchymal disease is discussed. Several alternative means of diagnosis of right diaphragmatic hernias are reviewed.

Clinical and genetic complexity of Mitchell-Riley/Martinez-Frias syndrome.

Mitchell-Riley syndrome/Martinez-Frias syndrome (MRS/MFS) is a rare, autosomal recessive disorder with multisystem involvement and poor prognosis. Most reported cases have been associated with homozygous or compound heterozygous mutations in the RFX6 gene, a transcriptional regulatory factor for pancreatic morphogenesis. Given the limited number of reported cases, the syndrome may be under-recognized. When the particular phenotype of MFS includes a mutation on the RFX6 gene and neonatal diabetes, it has been called Mitchell-Riley syndrome. Because of this, we propose that MFS/MRS is a symptom continuum or an RFX6 malformation complex. We report an infant with all of the key clinical features of MRS/MFS without a definable mutation in RFX6 gene, supporting the consideration of these features as a symptom complex, and raising the question of genetic heterogeneity.

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)

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.

Plasma lecithin: cholesterol acyltransferase and plasma lipolytic activity in preterm infants given total parenteral nutrition with 10% or 20% Intralipid.

The effect of 10% or 20% Intralipid on lipid clearing enzymes, plasma lipids and apoproteins was investigated during the first 5 days after birth in 37 premature infants maintained on total parenteral nutrition; 21 infants received 20% and 16 received 10% Intralipid, respectively. Lipid was infused over a 20-h period at rates of 1, 2 and 3 g/kg/day on consecutive days. Plasma lecithin: cholesterol acyltransferase (LCAT) activity was low and increased significantly (p<0.05) only during infusions of 3 g/kg/day in both groups of infants. Plasma lipolytic activity was generally not affected by the regimen or preparation (10% or 20%) of Intralipid infused, except for higher (p<0.05) levels at 3 g/kg/day of 20% compared with prelipid infusion. Plasma triglyceride concentrations wer similar after 10% or 20% Intralipid, whereas plasma total cholesterol was significantly higher during infusion of 2 and 3 g/kg/day of 10% compared with 20% Intralipid. The efficient clearing of 20% Intralipid might be related to the lower lecithin: triglyceride ration which is compatible with the low LCAT activity of premature infants.

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.

Passive jejunal bile salt absorption alters the enterohepatic circulation in immature rats.

BACKGROUND: Developmental changes in passive bile salt absorption may alter the enterohepatic circulation. METHODS: 14-, 21-, and 40-day-old anesthetized male Sprague-Dawley rats were studied. Jejunum and ileum were isolated, cannulated, and injected or perfused with a taurocholate, [3H]taurocholate, and nonabsorbable marker solution. Bile was collected. RESULTS: Using bolus injection, jejunal taurocholate absorption rates and total taurocholate absorption were nonsaturable, linearly related to taurocholate dose, and decreased from 14 days (1.62 nmol.cm-1.min-1) to 21 days (1.05 nmol.cm-1.min-1) and 40 days (0.54 nmol.cm-1.min-1). While total taurocholate absorption decreased (14 days, 52.4%; 21 days, 43.7%; 40 days, 30.5%), hepatic taurocholate clearance increased (14 days, 18.2%; 21 days, 23.7%; 40 days, 37.3%). Hepatic taurocholate clearance was saturated only at 14 days. Using jejunal perfusion, total taurocholate absorption (14 days, 62.0%; 21 days, 43.1%; 40 days, 45.3%) and taurocholate absorption rate decreased with age (14 days, 941.13 nmol.cm-2.min-1 per micromole of taurocholate; 21 days, 411.28 nmol.cm-2.min-1 per micromole of taurocholate; 40 days, 334.50 nmol.cm-2.min-1 per micromole of taurocholate). CONCLUSIONS: Passive jejunal bile salt absorption and decreased hepatic bile salt clearance could account for the low intraluminal and high serum bile salt levels observed in immature animals and in human neonates.

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)