C M Cotten

Congenital diaphragmatic hernia: a systematic review and summary of best-evidence practice strategies.

Objectives:Recent reports suggest that specific care strategies improve survival of infants with congenital diaphragmatic hernia (CDH). This review presents details of care from centers reporting high rates of survival among CDH infants.Study Design:We conducted a MEDLINE search (1995 to 2006) and searched all citations in the Cochrane Central Register of Controlled Trials. Studies were included if they contained reports of >20 infants with symptomatic CDH, and >75% survival of isolated CDH.Result:Thirteen reports from 11 centers met inclusion criteria. Overall survival, including infants with multiple anomalies, was 603/763 (79%; range: 69 to 93%). Survival for isolated CDH was 560/661 (85%; range: 78 to 96%). The frequency of extracorporeal membrane oxygenation (ECMO) use for isolated CDH varied widely among reporting centers 251/622 (40%; range: 11 to 61%), as did survival for infants with isolated CDH placed on ECMO: 149/206 (73%; range: 33 to 86%). There was no suggestion of benefit from use of antenatal glucocorticoids given after 34 weeks gestation or use of postnatal surfactant. Low mortality was frequently attributed to minimizing lung injury and adhering to center-specific criteria for ECMO.Conclusion:Use of strategies aimed at minimizing lung injury, tolerance of postductal acidosis and hypoxemia, and adhering to center-specific criteria for ECMO were strategies most consistently reported by successful centers. The literature lacks randomized clinical trials of these or other care strategies in this complex patient population; prospective studies of safety and long-term outcome are needed.

Mortality following blood culture in premature infants: increased with Gram-negative bacteremia and candidemia, but not Gram-positive bacteremia.

OBJECTIVE: To describe survival following nosocomial bloodstream infections and quantify excess mortality associated with positive blood culture.STUDY DESIGN: Multicenter cohort study of premature infants.RESULTS: First blood culture was negative for 4648/5497 (78%) of the neonates — 390/4648 (8%) died prior to discharge. Mortality prior to discharge was 19% in the 161 infants with Gram-negative rod (GNR) bacteremia, 8% in the 854 neonates with coagulase negative staphylococcus (CONS), 6% in the 169 infants infected with other Gram-positive bacteria (GP-o), and 26% in the 115 neonates with candidemia. The excess 7-day mortality was 0% for Gram-positive organisms and 83% for GNR bacteremia and candidemia. Using negative blood culture as referent, GNR [hazard ratio (HR)=2.61] and candidemia (HR=2.27) were associated with increased mortality; CONS (HR=1.08) and GP-o (HR=0.97) were not.CONCLUSIONS: Nosocomial GNR bacteremia and candidemia were associated with increased mortality but Gram-positive bacteremia was not.

Use of Medications for Gastroesophageal Reflux at Discharge Among Extremely Low Birth Weight Infants

OBJECTIVES. Our goals were (1) to determine the use of medications to treat gastroesophageal reflux in extremely low birth weight infants (birth weight of <1000 g) at discharge; (2) to identify risk factors associated with the use of medications to treat gastroesophageal reflux at discharge; and (3) to assess the contribution of gastroesophageal reflux medication use at discharge to growth and development at corrected ages of 18 to 22 months. METHODS. This retrospective cohort analysis included extremely low birth weight infants enrolled at National Institute of Child Health and Human Development Neonatal Research Network Centers between 2002 and 2003 who survived to follow-up evaluations at corrected ages of 18 to 22 months. Analyses were used to identify factors associated with discharge with antireflux medications and poor growth or neurodevelopmental impairment after discharge. RESULTS. A total of 1598 infants were included in the analyses; 24.8% were discharged from the hospital with medications to treat gastroesophageal reflux. A total of 19.3% of the 1287 infants discharged at postmenstrual age of ≤42 weeks were discharged with antireflux medications. For those infants, center, lower gestational age, and race had significant effects on the use of antireflux medications at discharge. A total of 47.6% of the 311 infants discharged at postmenstrual age of >42 weeks were discharged with antireflux medications. For those infants, no tested variables were associated with treatment with antireflux medications at discharge. Use of antireflux medications at discharge was not associated with either poor growth or neurodevelopmental impairment at corrected ages of 18 to 22 months. CONCLUSIONS. Use of antireflux medications at the time of discharge seems to be common for extremely low birth weight infants, especially those discharged at postmenstrual age of >42 weeks, but does not seem to have effects on growth or development at the time of follow-up evaluations.

Long-term morbidities associated with vocal cord paralysis after surgical closure of a patent ductus arteriosus in extremely low birth weight infants

Objective:Determine associations between left vocal cord paralysis (LVCP) and poor respiratory, feeding and/or developmental outcomes in extremely low birth weight (ELBW) infants following surgical closure of a patent ductus arteriosus (PDA).Study Design:ELBW infants who underwent PDA ligation between January 2004 and December 2006 were identified. We compared infants with and without LVCP following ligation to determine relationships between LVCP and respiratory morbidities, feeding and growth difficulties and neurodevelopmental impairment at 18 to 22-month follow-up. Students t-test, Fishers exact test and multivariable regression analyses were used to determine associations.Result:In all, 60 ELBW infants with a mean gestational age of 25 weeks and mean birth weight of 725 g had a PDA surgically closed. Twenty-two of 55 survivors (40%) were diagnosed with LVCP post-operatively. Infants with LVCP were significantly more likely to develop bronchopulmonary dysplasia (82 vs 39%, P=0.002), reactive airway disease (86 vs 33%, P<0.0001), or need for gastrostomy tube (63 vs 6%, P<0.0001).Conclusion:LVCP as a complication of surgical ductal ligation in ELBW infants is associated with persistent respiratory and feeding problems. Direct laryngoscopy should be considered for all infants who experience persistent respiratory and/or feeding difficulties following PDA ligation.

Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures

Objective:The purpose of this study was to examine the frequency of normal cerebrospinal fluid (CSF) parameters in Candida meningitis and the proportion of candidemia associated with Candida meningitis.Study design:We evaluated the initial lumbar puncture results from infants discharged from 150 Neonatal Intensive Care Units between 1997 and 2004. Candida meningitis was diagnosed by a positive CSF culture or positive Gram stain for yeast. We calculated two-tailed P-values using non-parametric testing, Mann–Whitney, Kruskal–Wallis or Fishers exact tests where appropriate.Results:Twenty infants had culture-positive Candida meningitis. Normal CSF parameters were found in 43% (3/7) of the infants with Candida meningitis and only 37% (7/19) of them had positive blood cultures for Candida.Conclusion:Normal CSF parameters do not exclude the diagnosis of neonatal Candida meningitis. The majority of infants in this cohort with Candida meningitis did not have evidence of candidemia at the time of diagnosis.

Caspofungin for the treatment of azole resistant candidemia in a premature infant.

Candidemia is common in extremely low birth weight infants and is associated with substantial mortality and morbidity. Treatment options have traditionally been limited to amphotericin B deoxycholate or fluconazole. We present a case of a premature infant with persistent candidemia despite antifungal treatment that responded to therapy with caspofungin, an echinocandin antifungal. The infants Candida isolate developed resistance to azoles during fluconazole administration and also suffered from severe hypercalcemia during the initiation of caspofungin therapy.

Transpyloric tube feeding in very low birthweight infants with suspected gastroesophageal reflux: impact on apnea and bradycardia.

Objective:Our aim was to assess the safety and efficacy of transpyloric tube feeding as a therapeutic option to reduce apnea and bradycardia in hospitalized very low birthweight (VLBW) infants with clinical signs suggestive of gastroesophageal reflux (GER).Study Design:This was a retrospective single-center cohort study of VLBW infants hospitalized from 2001 to 2004 with signs of GER who received transpyloric enteral tube feedings. Apnea (>10 s) and bradycardia (<100 bpm) episodes were compared before and after the initiation of transpyloric feedings. The Wilcoxon signed-rank test was used to compare differences between cardiorespiratory episodes before and after treatment at 1-day and combined 3-day intervals. Events recorded to assess the safety of transpyloric feedings included death, sepsis and necrotizing enterocolitis (NEC).Results:A total of 72 VLBW infants with a median birthweight of 870 g (ranging from 365 to 1435 g) and gestational age of 26 weeks (from 23 to 31 weeks) were identified. The median weight at initiation of transpyloric feedings was 1297 g (from 820 to 3145 g) and infants received transpyloric feeds for a median duration of 18 days (from 1 to 86 days). After the initiation of transpyloric feedings, a reduction in apnea episodes from 4.0 to 2.5 (P=0.02) and a decrease in bradycardia episodes from 7.2 to 4.5 (P<0.001) was observed when comparing the total number of episodes for the 3 days before and after treatment. Five (6.9%) of the infants developed NEC while receiving transpyloric feedings. None of the infants receiving human milk (P=0.07) and 36% of those receiving hydrolysate-based formula (P<0.01) during transpyloric feeds developed NEC. No infants had late-onset culture-proven sepsis. Seven (9.7%) infants died before hospital discharge.Conclusions:Transpyloric feedings, especially when limited to human milk, may safely reduce episodes of apnea and bradycardia in preterm infants with suspected GER. Prospective randomized studies are needed to determine the biological impact of bypassing the stomach, as well as the safety and efficacy of this intervention. The results of such studies could modify the current prevailing safety concerns regarding transpyloric feeding in this population.

A comparison of neonatal Gram-negative rod and Gram-positive cocci meningitis.

Objective:Neonatal meningitis is an illness with potentially devastating consequences. Early identification of potential risk factors for Gram-negative rod (GNR) infections versus Gram-positive cocci (GPC) infection prior to obtaining final culture results is of value in order to appropriately guide expirical therapy. We sought to compare laboratory and clinical parameters of GNR and GPC meningitis in a cohort of term and premature infants.Study Design:We evaluated lumbar punctures from neonates cared for at 150 neonatal intensive care units managed by the Pediatrix Medical Group Inc. We compared cerebrospinal fluid (CSF) parameters (white blood cell count, red blood cell count, glucose, and protein), demographics, and outcomes between infants with GNR and GPC meningitis. CSF cultures positive with coagulase-negative staphylococci were excluded.Results:We identified 77 infants with GNR and 86 with GPC meningitis. There were no differences in gestational age, birth weight, infant sex, race, or rate of Caesarean section. GNR meningitis was more often diagnosed after the third postnatal day and was associated with higher white blood cell and red blood cell counts. GNR meningitis diagnosed in the first 3 days of life was associated with antepartum antibiotic exposure. No difference was noted in either CSF protein or glucose levels. After correcting for gestational age, there was no observed difference in mortality between infants infected with GNR or GPC.Conclusion:Compared to GPC meningitis, GNR meningitis was associated with several aspects of the clinical history and laboratory findings including older age of presentation, antepartum exposure to antibiotics, and elevated CSF white blood cell and red blood cell counts.

Does IVIg administration yield improved immune function in very premature neonates

Intravenous immunoglobulin (IVIg) has been evaluated as an adjunctive therapy for neonatal sepsis with modest clinical success despite strong biological plausibility. Multiple factors contribute to this outcome, but perhaps none greater than the limited immune system function in newborns, especially in the very premature neonates. For very premature neonates (<30 weeks gestational age), understanding the effects of IVIg on specific immature immune system functions is particularly relevant given their preponderance to develop sepsis and therefore potentially benefit from IVIg-mediated immunoenhancement. Here, we review the available evidence for enhanced immune function after IVIg administration in very premature neonates and highlight areas for future research.

Impact of a Palliative Care Program on End-of-life Care in a Neonatal Intensive Care Unit

Objective:Evaluate changes in end-of-life care following initiation of a palliative care program in a neonatal intensive care unit.Study design:Retrospective study comparing infant deaths before and after implementation of a Palliative Care Program comprised of medication guidelines, an individualized order set, a nursing care plan and staff education.Result:Eighty-two infants died before (Era 1) and 68 infants died after implementation of the program (Era 2). Morphine use was similar (88% vs 81%; P =0.17), whereas benzodiazepines use increased in Era 2 (26% vs 43%; P=0.03). Withdrawal of life support (73% vs 63%; P=0.17) and do-not-resuscitate orders (46% vs 53%; P=0.42) were similar. Do-not-resuscitate orders and family meetings were more frequent among Era 2 infants with activated palliative care orders (n=21) compared with infants without activated orders (n=47).Conclusion:End-of-life family meetings and benzodiazepine use increased following implementation of our program, likely reflecting adherence to guidelines and improved communication.