Bhagya L. Puppala

A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus immune globulin

Objectives:Very low birth weight (VLBW) infants are vulnerable to nosocomial infections and subsequent morbidity; including infections caused by Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph™ is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG.Methods:A Phase 2 clinical trial to assess the safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter study were randomized to receive two identical 20 ml/kg i.v. infusions of either 0.45% NaCl placebo or 1000 mg Altastaph/kg. Each infant was followed for 28 days after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8 IgG levels were measured preinfusion and at various times after each infusion.Results:Of 206 neonates, 158 received both infusions. Adverse events were similar in the two treatment groups. Six subjects (3% in each group) discontinued owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642 mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses, respectively, in neonates ⩽1000 g and slightly higher in neonates 1001 to 1500 g. Trough levels before second infusion were 188 mcg/ml. Type 8 IgG levels were similar. Geometric mean IgG levels among placebo recipients were consistently <2 and <5 mcg/ml for types 5 and 8 in both weight groups. Three episodes of S. aureus bacteremia occurred in each arm.Conclusions:Infusion of Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5 and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune globulin was well tolerated in this population.

Procalcitonin as a Screening Test for Late-Onset Sepsis in Preterm Very Low Birth Weight Infants

OBJECTIVE:To compare the utility of procalcitonin (PCT) vs C-reactive protein (CRP) as indicators of late-onset neonatal sepsis in very low birth weight (VLBW) infants.METHODS:PCT and CRP levels were measured in VLBW infants with suspected sepsis and controls. Comparisons were made between infected vs noninfected infants. Using cutoff values of 0.5 and 1.0 ng/ml for PCT and 0.8 mg/dl for CRP, sensitivity, specificity, positive and negative predictive values were calculated to evaluate these assays as potential predictors of late-onset sepsis.RESULTS:A total of 67 infants were evaluated. Mean PCT levels were significantly higher in the infected group (5.41 ng/ml) compared to the noninfected group (0.43 ng/ml) (p<0.001). At a cut off value of 0.5 ng/ml, the sensitivity of PCT was 97%, whereas that of CRP was 73% in predicting late-onset sepsis. At a PCT cutoff of 1.0 ng/ml, sensitivities of PCT and CRP were similar (72% each).CONCLUSION:PCT (0.5 ng/ml) is more sensitive than CRP in predicting late-onset sepsis in VLBW infants.

A randomized, double-blind, placebo-controlled trial of prophylactic recombinant human granulocyte-macrophage colony-stimulating factor to reduce nosocomial infections in very low birth weight neonates

OBJECTIVE We carried out a randomized placebo-controlled trial in very low birth weight neonates (VLBWNs), comparing the incidence of nosocomial infections after the prophylactic use of recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) versus placebo in VLBWNs. STUDY DESIGN VLBWNs (n = 264), weighing 501 to 1000 g, </=72 hours of age were randomly assigned to receive rhu GM-CSF (8 microg/kg/d), administered intravenously (n = 134) over 2 hours daily x 7 days and every other day for 21 days, or placebo (n = 130). The safety, incidence of nosocomial infections, days of absolute neutrophil count >/=4000/mm,3 peripheral blood progenitor studies, and 24-hour polymorphonuclear leukocyte C3bi receptor expression were compared between the 2 treatment groups. RESULTS No (grade III/IV) toxicity or adverse events were associated with rhu GM-CSF. The absolute neutrophil count and absolute eosinophil count were significantly elevated in the rhu GM-CSF group on days 7 (P =.001), 14 (P =.001), and 21 (P =.007) and on days 7 and 28 (P =.012 and P =.001, respectively). However, there was no difference in the incidence of confirmed nosocomial infections between the 2 treatment groups in this trial (40% vs 39%, rhu GM-CSF vs placebo; P = NS). CONCLUSION In a large randomized placebo-controlled trial, prophylactic administration of rhu GM-CSF in VLBWNs does not appear to decrease the incidence of nosocomial infections.

Outcomes of Early Nutrition Support in Extremely Low-Birth-Weight Infants

BACKGROUND Early nutrition intervention, both parenteral and enteral, is becoming a standard of care for the extremely low-birth-weight infant (ELBW; <1,000 g) in many neonatal intensive care units (NICU) across the United States. However, there are no published or widely accepted guidelines regarding nutrition support strategies for this population. Most NICU clinicians have developed their own guidelines, so nutrition practices vary widely. In an effort to standardize our practice, we implemented nutrition support guidelines for ELBW infants, initiating both parenteral nutrition (PN) and minimal enteral feedings (MEFs) within the first 24 hours of life, whenever possible. The purpose of this study was 2-fold: (1) to evaluate the adherence to the nutrition guidelines and (2) to compare pre- and postguideline outcomes such as time to regain birth weight, time to reach full enteral feedings, and average daily weight gains. METHODS The study was conducted at a level III NICU from January 2002 until February 2003. Charts of 70 infants with a birth weight <or=1,250 g were reviewed as part of a quality-assurance project to monitor adherence to the newly established guidelines. Another 23 charts of ELBW infants who were admitted and cared for in the NICU before the initiation of the nutrition guidelines were reviewed as a control group. Data collected from the charts included the hour of life PN and MEFs were started, the day of life infants reached full enteral feedings, infant weights for the first 4 weeks of life, incidence of early hyperglycemia, occurrence of necrotizing enterocolitis, and length of neonatal birth hospital stay. Students t-tests were used to compare clinical outcomes between infants receiving early nutrition support (<or=24 hours of life) vs those who were started later. RESULTS Of eligible infants, 82.6% began receiving nutrition support within 24 hours of life. The average time to begin PN was 22 hours after the adoption of the guidelines vs 64.4 hours before guideline implementation (p < .01). In the postguideline group, MEFs were initiated at mean 27.1 hours of age vs 80.4 hours in the preguideline group (p < .01). Those who were started on early nutrition support reached full enteral feedings significantly sooner than those who received delayed nutrition support (12.7 days vs 45.8 days; p < .01). Early nutrition support also resulted in earlier regain of birth weight (day 13.3 vs 15.4 days, p < .05). Although not statistically significant, infants who received earlier nutrition support showed trends toward greater overall weight gain in weeks 3 and 4 of life and a lower incidence of elevated serum blood glucose. CONCLUSIONS The implementation of early nutrition support guidelines influenced the timeliness of initiating nutrition support in our unit. Early initiation of nutrition support in ELBW infants produces a rapid regain of initial weight loss, improves weight gain, and enhances earlier achievement of full enteral feedings.

Nasal Glioma Presenting as Neonatal Respiratory Distress Definition of the Tumor Mass by MRI

Nasal gliomas are benign congenital midline tumors with the potential for intracranial extension. They are most commonly seen in neonates and children but rarely in adults. The treatment of choice is surgical excision. Inadequate primary excision results in a 4 to 10 percent recurrence. Hence, a thorough preoperative evaluation is essential to delineate the exact site and extension of the tumor and to plan the appropriate surgical approach. Computerized tomographic (CT) scans are useful in visualizing bony defects, but are not well suited for soft tissue imaging. Magnetic resonance imaging (MRI) offers superior soft tissue contrast, without ionizing radiation. This is a report of a neonate with unexplained early respiratory distress. On day 5, a soft nasal mass became apparent. CT scans were inconclusive, so MRI scan was used to demonstrate intracranial extension. MRI is superior for imaging brain tissue, so it should be used preferentially to delineate intracranial extension and to help guide the surgical approach.

Incidence and duration of hepatitis B surface antigenemia after neonatal hepatitis B immunization

After immunization with recombinant hepatitis B vaccine, 19 infants were tested serially for hepatitis B surface antigen (HBsAg); 65% of infants had test results positive for HBsAg at least once, the incidence peaking 2 to 3 days from the time of immunization. The longest documented duration of antigenemia was 8 days; in all patients, HBsAg test results were negative by 18 days.

Familial occurrence of congenital colonic atresia

Patient 1. A term male infant was transferred to the Newborn Intensive Care Unit from another hospital at 60 hours of age because of progressive abdominal distention, vomiting, poor feeding, lethargy~ and failure to pass stools since birth. The infant had been born to a 26-year-old unmarried mother, gravida 2, para 1. The pregnancy was unremarkable until two weeks prior to delivery, when the mother develoPed edema of the hands and feet, whichwas treated with a diuretic. The membranes ruptured spontaneously one hour prior to delivery, revealing clear amniotic fluid. Hydramnios was not noted. Birth weight was 3,076 gin. Initial physical examination revealed slight abdominal distention with no obvious malformations. Nipple feedings were taken poorly, followed by vomiting of bile-stained material. At 12 hours he passed a mucous plug per rectum. The abdominal distention progressively increased. Rectal examination revealed no meconium in the rectum. An abdominal radiograph revealed generalized distention of small and large bowel, with feces in the flanks and no air in the rectum. A saline retention enema was administered, without return of stool. The infant was transferred for further evaluation and treatment. Following admission to the Neonatal Intensive Care Unit, a barium enema was administered and revealed abrupt termination of barium in the distal sigmoid, with microcolon. At laparotomy the proximal colon was found to be enormously

Airborne concentrations of volatile organic compounds in neonatal incubators

Objective:To identify and quantify airborne volatile organic compounds (VOCs) inside neonatal incubators during various modes of operation within the neonatal intensive care unit (NICU) environment.Study Design:Air samples were taken from 10 unoccupied incubators in four operational settings along with ambient air samples using air sampling canisters. The samples were analyzed following EPA TO-15 using a Tekmar AutoCan interfaced to Agilent 6890 Gas Chromatograph with a 5973 Mass Spectrometer calibrated for 60 EPA TO-15 method target compounds. Non-target compounds were tentatively identified using mass spectral interpretation and with a mass spectral library created by National Institute for Standards and Technology.Result:Two non-target compounds, 2-heptanone and n-butyl acetate, were found at elevated concentrations inside the incubators compared with ambient room air samples. Increase in temperature and addition of humidity produced further increased concentrations of these compounds. Their identities were verified by mass spectra and relative retention times using authentic standards. They were quantified using vinyl acetate and 2-hexanone as surrogate standards.Conclusion:The emission pattern of these two compounds and background measurements indicate that they originate inside the incubator. There is evidence that exposure to some VOCs may adversely impact the fetal and developing infants’ health. Currently, as there is no definitive information available on the effects of acute or chronic low-level exposure to these compounds in neonates, future studies evaluating the health effects of neonatal exposure to these VOCs are needed.

Neonatal Distal Femoral Physeal Fracture Requiring Closed Reduction and Pinning

Neonatal physeal fracture of the distal femur is often difficult to diagnose. Timely and accurate diagnosis and appropriate therapy are critical in order to avoid permanent morbidity and dysfunction of the affected limb. We describe an infant in whom closed reduction and pinning were required in order to assure a good outcome.

Distal ileostomy drip feedings in neonates with short bowel syndrome

When a newborn infant presents with high intestinal atresia, the proximal segment of the bowel is usually grossly distended and atonic. The anastomosis of this segment to the smaller and unused distal segment will usually result in little or no propulsion of contents distally. Many techniques have been employed to correct this problem. A common surgical approach is immediate end-to-end anastomosis, followed by parenteral alimentation until return of normal function. This can take many weeks, and requires special attention to fluid loss and complications associated with parenteral alimentation. In this paper we report two infants in whom we utilized a new technique to circumvent these problems. The technique involves continuous drip ileostomy feedings through the distal ileostomy, while basic nutritional needs are being met parenterally. In addition, the secretions from the proximal stoma are collected and infused with the elemental feeding. The distal bowel, now being fully utilized, is stimulated to accommodate, and when the two ends are joined at a second operation, nearly normal anatomical bowel is present.