Jeffery S. Garland

Neonatal Cord Blood Leptin: Its Relationship to Birth Weight, Body Mass Index, Maternal Diabetes, and Steroids

Leptin is a 16-kD protein encoded by the ob/ob (obesity) gene. In rodents it plays a role in obesity, diabetes, fertility, and neuroendocrine function. In humans serum concentrations of leptin correlate with total body fat in both adults and children. We measured cord blood leptin in 186 neonates that included 82 appropriate for gestational age (AGA), 47 large for gestational age (LGA), 20 infants of diabetic mothers, 52 preterm infants, and 15 intrauterine growth-retarded (IUGR) infants. There were 16 pairs of twins. The mothers of 17 preterm infants were treated with steroids before delivery. Leptin (mean ± SD) concentration in term, AGA infants (39.4 ± 1.1 wk) with birth weight (BW) of 3.2 ± 0.3 kg, body mass index (BMI) of 12.6 ± 1.1 was 4.01 ± 3.5 ng/mL. BW correlated with cord leptin (p = 0.002) in a multivariate analysis controlling for potential confounders. Both LGA infants and infants of diabetic mothers had higher cord leptin concentration 7.3 ± 3.8 and 6.1 ± 4.8 ng/mL, respectively, compared with AGA infants (p < 0.05). Preterm infants had a mean leptin level of 1.8 ± 0.97 ng/mL and a 3-fold elevation was seen if mothers received steroids antenatally (p = 0.006). IUGR infants had increased leptin (6.5 ± 3.9 ng/mL, p= 0.03). Concerning the twin pairs, the smaller had a higher leptin level compared with larger twin (4.1 ± 9.51 versus 2.8 ± 5.14, p = NS). Neonatal cord leptin concentrations correlate well with BW and BMI. No gender differences were found in cord blood leptin. Maternal obesity had no effect on cord leptin, whereas exogenous maternal steroids increased neonatal leptin concentrations.

Comparison of 10% povidone-iodine and 0.5% chlorhexidine gluconate for the prevention of peripheral intravenous catheter colonization in neonates : a prospective trial

The purpose of the study was to compare the efficacy of 10% povidone-iodine with that of 0.5% chlorhexidine gluconate in 70% isopropyl alcohol for the prevention of peripheral intravenous catheter colonization in neonates. This was a multicenter, nonrandomized prospective study in a tertiary neonatal intensive care setting in which povidone-iodine and chlorhexidine gluconate were each used as antiseptic skin preparations over sequential 6-month periods. During the first 6 months of the study when povidone-iodine was in use 9.3% (38 of 408) of catheters were colonized. During the second 6 months of the study when chlorhexidine gluconate was in use, catheter colonization occurred in 4.7% (20 of 418, P = 0.01). Catheter-related bacteremia occurred during only 0.2% (2 of 826) of all catheterizations. Heavy skin colonization before catheter insertion (relative risk, 3.6; 95% confidence interval, 1.9, 7.0), catheterization > or = 72 hours (relative risk. 2.0; 95% confidence interval, 1.01, 3.8) and gestational age < or = 32 weeks (relative risk, 1.8; 95% confidence interval, 1.02, 3.3) increased colonization risk. Ampicillin infusion (relative risk, 0.4; 95% confidence interval, 0.2, 0.7) and 0.5% chlorhexidine gluconate cutaneous antisepsis (relative risk, 0.4; 95% confidence interval, 0.2, 0.8) were factors associated with decreased colonization risk. We conclude that 0.5% chlorhexidine gluconate in 70% isopropyl alcohol appears to be more efficacious than 10% povidone-iodine for the prevention of peripheral intravenous catheter colonization in neonates.

A vancomycin-heparin lock solution for prevention of nosocomial bloodstream infection in critically ill neonates with peripherally inserted central venous catheters: a prospective, randomized trial.

Objective.Critically ill neonates are at high risk for vascular catheter–related bloodstream infection (CRBSI), most often caused by coagulase-negative staphylococci. Most CRBSIs with long-term devices derive from intraluminal contaminants. The objective of this study was to ascertain the safety and the efficacy of a vancomycin-heparin lock solution for prevention of CRBSI. Methods.A prospective, randomized double-blind trial was conducted during 2000–2001 at a community hospital level III NICU. Very low birth weight and other critically ill neonates with a newly placed peripherally inserted central venous catheter were randomized to have the catheter locked 2 or 3 times daily for 20 or 60 minutes with heparinized normal saline (n = 43) or heparinized saline that contained vancomycin 25 μg/mL (n = 42). The origin of each nosocomial bloodstream infection (BSI) was studied by culturing skin, catheter hubs, and implanted catheter segments and blood cultures, demonstrating concordance by restriction-fragment DNA subtyping. Surveillance axillary and rectal cultures were performed to detect colonization by vancomycin-resistant organisms. The main outcome measures were (1) CRBSIs and (2) colonization or infection by vancomycin-resistant Gram-positive bacteria. Results.Two (5%) of 42 infants in the vancomycin-lock group developed a CRBSI as compared with 13 (30%) of 43 in the control group (2.3 vs 17.8 per 1000 catheter days; relative risk: 0.13; 95% confidence interval: 0.01–0.57). No vancomycin-resistant enterococci or staphylococci were recovered from any cultures. Vancomycin could not be detected in the blood of infants who did not receive systemic vancomycin therapy. Twenty-six neonates (8 vancomycin-lock group, 18 control group) had at the end of a catheter-lock period asymptomatic hypoglycemia that resolved promptly when glucose-containing intravenous fluids were restarted. Conclusions.Prophylactic use of a vancomycin-heparin lock solution markedly reduced the incidence of CRBSI in high-risk neonates with long-term central catheters and did not promote vancomycin resistance but was associated with asymptomatic hypoglycemia. The use of an anti-infective lock solution for prevention of CRBSI with long-term intravascular devices has achieved proof of principle and warrants selective application in clinical practice.

A Three-day Course of Dexamethasone Therapy to Prevent Chronic Lung Disease in Ventilated Neonates: A Randomized Trial

Background. Although several trials of early dexamethasone therapy have been completed to determine if such therapy would reduce mortality and chronic lung disease (CLD) in infants with respiratory distress, optimal duration and side effects of such therapy remain unknown. Purpose. The purpose of this study was: 1) to determine if a 3-day course of early dexamethasone therapy would reduce CLD and increase survival without CLD in neonates who received surfactant therapy for respiratory distress syndrome and 2) to determine adverse effects associated with such therapy. Design. This was a prospective multicenter randomized trial comparing a 3-day course of dexamethasone therapy beginning at 24 to 48 hours of life to placebo therapy. Two hundred forty-one neonates (dexamethasone n = 118, placebon = 123), who weighed between 500 g and 1500 g, received surfactant therapy, and were at significant risk for CLD or death using a model to predict CLD or death at 24 hours of life, were enrolled in the trial. Infants randomized to receive early dexamethasone were given 6 doses of dexamethasone at 12-hour intervals beginning at 24 to 48 hours of life. The primary outcomes compared were survival without CLD and CLD. CLD was defined by the need for supplemental oxygen at the gestational age of 36 weeks. Complication rates and adverse effects of study drug therapy were also compared. Results. Neonates randomized to early dexamethasone treatment were more likely to survive without CLD (RR: 1.3; 95% CI: 1.03, 1.7) and were less likely to develop CLD (RR: 0.6; CI: 0.3, 0.98). Mortality rates were not significantly different. Subsequent dexamethasone therapy use was less in early dexamethasone-treated neonates (RR: 0.8; CI: 0.7, 0.96). Very early (≤7 days of life) intestinal perforations were more common among dexamethasone-treated neonates (8% vs 1%). Conclusion. We conclude that an early 3-day course of dexamethasone therapy increases survival without CLD, reduces CLD, and reduces late dexamethasone therapy in high-risk, low birth weight infants who receive surfactant therapy for respiratory distress syndrome. Potential benefits of early dexamethasone therapy at the dosing schedule used in this trial need to be weighed against the risk for early intestinal perforation.

Trends in mortality in children hospitalized with meningococcal infections, 1957 to 1987

We reviewed charts of 261 children seen at Childrens Hospital of Wisconsin from 1957 to 1987 with culture-proven meningococcemia or meningococcal meningitis, and we analyzed trends in mortality and disease severity for that interval. Overall case fatality was 10%, ranging from 9% in the period 1957 to 1963, to 16% in the period 1980 to 1987 (P = 0.15). The percent of patients admitted with severe disease increased from 14% to 38% (P = 0.001). When stratified by disease severity, case-fatality rates did not change with time. We conclude that technologic advances of the past 30 years had no measurable impact on mortality from meningococcal infection in our hospital and that crude case-fatality rates can be misleading if disease severity is not considered.

Infectious complications during peripheral intravenous therapy with Teflon catheters: a prospective study.

Infectious complication rates and associated risk factors occurring during peripheral intravenous therapy with Teflon catheters were determined during a prospective study of 286 cannula insertions. Suppurative phlebitis, cannula-related sepsis or suspected sepsis did not occur. Semiquantitative cannula cultures revealed a colonization rate of 10.4% (12 of 115). Coagulase-negative nonadherent Staphylococcus was the most common colonizing organism occurring in 10 of 12 positive catheters. Alpha Streptococcus and adherent coagulase-negative Staphylococcus colonized the remaining catheters. Colonization was not related to the rate of phlebitis, extravasation or cannulation time. No patient- or catheter-related factors increased the risk of colonization. In children in a general pediatric ward the risk of catheter colonization and subsequent sepsis should not be used as reasons for routinely removing complication-free peripheral Teflon catheters at 72 hours.

Safety of percutaneous endoscopic gastrostomy in medically complicated infants.

Background and Objective: Percutaneous endoscopic gastrostomy (PEG) tubes have been placed in children for more than 2 decades to provide nutrition to those unable to adequately and safely feed orally. Despite the well-documented success of PEG placement in older children, there is only 1 published article documenting the safety of PEG placement in small infants. In all children, PEG studies demonstrate the major complication rate to vary from 0.5% to 17%. The objective of this study was to evaluate the incidence of acute complications of PEG placement in medically complicated infants with a weight of less than 6 kg. Patients and Methods: We reviewed the charts of all infants cared for in the neonatal intensive care unit of Wheaton Franciscan Health Care-St Josephs Regional Hospital, Milwaukee, WI, who received a PEG tube between January 2001 and June 30, 2008. Results: Forty infants with a mean gestational age of 29 weeks (range 23–41 weeks) with a mean weight of 3250 g (range 2100–5600 g) at time of PEG placement were included. The primary indication for most infants was dysphagia or inability to orally feed safely. A PEG was successfully placed in 38 of 40 (95%) infants. There was 1 major complication: a 38-week infant with Prader-Willi syndrome developed a pneumomediastinum caused by a tear at the upper esophageal sphincter. In a second infant the PEG bumper could not be passed beyond the upper esophageal sphincter. Sixteen infants had other surgical procedures performed at the time of PEG placement. For those infants only having a PEG placed, the mean procedure time was 10 minutes. Conclusions: PEG placement is both feasible and safe in small, medically complicated infants.

Accidental cocaine intoxication in a nine-month-old infant: presentation and treatment

A case of a nine-month-old male who ingested cocaine is presented. The rarity of this type of ingestion, as well as the caretakers denial of the presence of cocaine in the household, made rapid diagnosis of this infants malady difficult. We present this case to alert physicians to the presentation and treatment of cocaine-intoxicated infants.

THE NATURAL HISTORY OF TEFLON CATHETER ASSOCIATED PHLEBITIS (PHL) IN CHILDREN

The purpose of this study was to examine the natural history of PHL during peripheral intravenous therapy with Teflon® catheters (TC). Sites (286) were selected randomly and inspected daily for signs of PHL. Sites that developed PHL were followed until symptoms resolved. A random sample of TC tips were cultured.Ten percent (30/286) of the sites developed PHL. TC induced sepsis did not occur and colonization was not associated with PHL. Factors associated with an increased risk of PHL were: nafcillin (p<.001), aminoglycosides (p<.01), parenteral nutrition (PN) (p<.009), age (older>younger, p<.008), race (white>black, p<.01) and cannulation time (>72 hours, p<.01). Multiple linear regression analysis using these variables revealed PN, nafcillin, aminoglycoside therapy and age as the most important determinants of the PHL rate. The mean onset and resolution time of PHL episodes was 69.2±39.3 hours (range 200 hours) and 39.5±26.8 hours (range 84 hours) respectively. In 9 cases, PHL was not fully developed until after the TC were removed. No factors hastened the onset of PHL and only PN prolonged the resolution time of PHL episodes. We conclude that the rate of PHL in children is less than that of recently published adult rates (18-23%). Phlebitis appears to be a minor complication during infusion therapy with TC.

Risk of morbidity following catheter removal among neonates with catheter associated bloodstream infection

OBJECTIVE We hypothesized that infectious morbidities following percutaneously inserted central venous catheter (PICC) removal would be greater among neonates with central-line associated bloodstream infection (CLBASI). STUDY DESIGN This retrospective cohort study, included all neonates who required a PICC over a ten-year period. Outcomes assessed following PICC removal included: late bloodstream infection, rule-out sepsis workups, need for a subsequent PICC and antibiotic days and PICC days after PICC removal. Odds ratios (OR) and 95% confidence intervals (CI) were determined for outcomes. Regression analyses were used to control for confounders. RESULTS Two-thousand nine hundred and thirteen neonates required at least one PICC during the study period. After adjusting for confounders neonates with CLABSI were 3.4 (95% confidence interval (CI) 2.5, 4.6) and 2.2 (95% CI 1.2, 4.0) times more likely respectively to require a subsequent PICC or develop a late bloodstream infection after PICC removal. Neonates with CLABSI required 1.33 (95% CI 0.77, 1.89) more days of antibiotic treatment and 6.85 (95% CI 5.34, 8.37) more PICC days following PICC removal than neonates without a CLABSI. CONCLUSIONS Neonates with CLABSI are at risk for additional infectious morbidities after PICC removal. Future intervention studies aimed at reducing CLABSI should evaluate whether morbidities following catheterization are also reduced.