Hany Aly

Is Bloodstream Infection Preventable Among Premature Infants? A Tale of Two Cities

Background. Bloodstream infection (BSI) is a significant cause of morbidity and death encountered in the NICU. The rates of BSIs vary significantly in NICUs across the nation. However, no attempt has been made to correlate this variation with specific infection-control practices and policies. We experienced a significant increase in BSIs in the NICU at the George Washington University Hospital and were seeking additional precautionary measures to reduce BSI rates. Our objective was to review policies and practices associated with lower infection rates nationally and to test their reproducibility in our unit. Design and Methods. Data on BSI rates in 16 NICUs were reviewed. The BSI rate at Connecticut Children’s Medical Center (CCMC) was the lowest among those reviewed. A team from George Washington University Hospital conducted a site visit to CCMC to examine their practices. Differences in the aseptic precautions used for intravenous line management were noted at CCMC, where a closed medication system is used. This system was applied at George Washington University Hospital starting January 1, 2001. Infection rates among low birth weight infants (<2500 g) at George Washington University Hospital in the period from January 1998 to December 2000 (group 1) were compared with those in the period from January 2001 to December 2003 (group 2). Comparisons between the 2 cohorts were made with Fisher’s exact test, the Kruskal-Wallis test, and Student’s t test. Multivariate analysis was used to control for differences in birth weight, gestational age, central line days, and ventilator days. Analyses were repeated for the subgroup of very low birth weight infants (<1500 g). Results. A total of 536 inborn low birth weight infants were included in this retrospective study (group 1, N = 169 infants; group 2, N = 367). The incidence of sepsis decreased significantly from group 1 to group 2 (25.4% and 2.2%, respectively). The reduction of sepsis observed in association with the new practice was statistically significant after controlling for birth weight, central line days, and ventilator days in a multiple regression model (regression coefficient: 0.95 ± 0.29). The odds ratio of reduction in sepsis after implementation of the new practice was 2.6 (95% confidence interval: 1.5–4.5). The central line-related BSI rate decreased from 15.17 infections per 1000 line days to 2.1 infections per 1000 line days. The study included 233 very low birth weight infants, ie, 90 in group 1 and 143 in group 2. The rate of BSIs decreased significantly from group 1 to group 2 (46.7% and 5.6%, respectively). The decrease in sepsis rate remained significant in a multiple regression model (regression coefficient: 1.42 ± 0.35). The odds ratio of decreased sepsis in relation to the new policy application among the very low birth weight infants was 4.15 (95% confidence interval: 2.1–8.3). Conclusion. Applying the closed medication system was associated with reduced BSI rates in our unit. This protocol was easily reproducible in our environment and showed immediate results. Serious attempts to share data can potentially optimize outcomes and standardize policies and practices among NICUs.

Human Recombinant Erythropoietin in Asphyxia Neonatorum: Pilot Trial

OBJECTIVE: The goal was to examine biochemical, neurophysiologic, anatomic, and clinical changes associated with erythropoietin administration to neonates with hypoxic-ischemic encephalopathy (HIE). METHODS: We conducted a prospective case-control study with 45 neonates in 3 groups, a normal healthy group (N = 15), a HIE-erythropoietin group (N = 15; infants with mild/moderate HIE who received human recombinant erythropoietin, 2500 IU/kg, subcutaneously, daily for 5 days), and a HIE-control group (N = 15; did not receive erythropoietin). Serum concentrations of nitric oxide (NO) were measured at enrollment for the normal healthy neonates and at enrollment and after 2 weeks for the 2 HIE groups. The 2 HIE groups underwent electroencephalography at enrollment and at 2 to 3 weeks. Brain MRI was performed at 3 weeks. Neurologic evaluations and Denver Developmental Screening Test II assessments were performed at 6 months. RESULTS: Compared with normal healthy neonates, the 2 HIE groups had greater blood NO concentrations (P < .001). At enrollment, the 2 HIE groups did not differ in clinical severity, seizure incidence, NO concentrations, or electroencephalographic findings. At 2 weeks of age, electroencephalographic backgrounds improved significantly (P = .01) and NO concentrations decreased (P < .001) in the HIE-erythropoietin group, compared with the HIE-control group; MRI findings did not differ between groups. At 6 months of age, infants in the HIE-erythropoietin group had fewer neurologic (P = .03) and developmental (P = .03) abnormalities. CONCLUSION: This study demonstrates the feasibility of early administration of human recombinant erythropoietin to term neonates with HIE, to protect against encephalopathy.

Red blood cell transfusion, feeding and necrotizing enterocolitis in preterm infants.

Objective:Preliminary studies suggested an association between red blood cell (RBC) transfusion and necrotizing enterocolitis (NEC) in premature neonates. An advantageous effect of withholding feeds during transfusion has never been studied. We aimed, first, to determine whether preterm infants who developed NEC were more likely to be transfused in the 48 to 72 h before the diagnosis of NEC; second, to test if a strict policy of withholding feeds during transfusion would decrease the incidence of transfusion-associated NEC.Study Design:The study was conducted in two phases. Phase 1: a retrospective case–control study of premature low-birth weight (<32 weeks and <2500 g) infants who developed NEC over a 6-year period. Phase 2: a comparison study of the incidence of NEC during the 18-months preceding, and the 18 months following the change of practice to withholding feeds during RBC transfusion.Result:In the case–control study (25 infants with NEC and 25 controls), more infants in the NEC group received transfusions in the 48 and 72 h preceding diagnosis (56 vs 20% within 48 h, P=0.019; and 64 vs 24% within 72 h, P=0.01). The total number of transfusions and age of RBCs were not different between the two groups. Implementing the policy of withholding feeds during transfusion was associated with a decrease in the incidence of NEC from 5.3 to 1.3% (P=0.047).Conclusion:Infants who developed NEC frequently received RBC transfusions in the 48 and 72 h preceding presentation of NEC. A strict policy of withholding feeds during transfusion may have a protective effect from NEC.

Does the Experience With the Use of Nasal Continuous Positive Airway Pressure Improve Over Time in Extremely Low Birth Weight Infants

Objective. Early use of nasal continuous positive airway pressure (ENCPAP) in extremely low birth weight (ELBW) infants continues to be a source of debate. Centers are applying this management strategy with varying success. Our center has implemented this strategy of care over the past 4 years, and the objective of this study was to evaluate the impact of experience over time with the use of ENCPAP on outcomes of ELBW infants. Methods. All ELBW infants who were born at our hospital since the institution of the ENCPAP practice (n = 101) were analyzed retrospectively. Patients were divided into 3 terciles according to their birth date. A baseline group of ELBW infants who were born in the 2 years preceding the institution of the ENCPAP practice (group 0; n = 45) were used for comparison. Trends in practices and outcomes over time were analyzed using the 2-sided Cochran-Armitage linear trend test. Statistical significance for these trends were then analyzed again using a multivariate regression model controlling for significant variables. Bivariate analyses comparing individual groups were also conducted. Results. There were no significant trends in mortality rate among the baseline group and the 3 terciles since the institution of the ENCPAP practice (26.7% vs 26.5% vs 11.8% vs 18.2%). ENCPAP management increased in the surviving infants over time (14% vs 19.2% vs 65.52% vs 70.4%), whereas the use of surfactant decreased (51.5% vs 48% vs 13.3% vs 33.3%) and the incidence of bronchopulmonary dysplasia (BPD) decreased (33.3% vs 46.2% vs 25.9% vs 11.1%). The average ventilator days per infant decreased, the rate of sepsis decreased, and the average daily weight gain increased. There were no significant trends in the incidence of intraventricular hemorrhage or necrotizing enterocolitis (NEC). When comparing the cohorts of survivors in the 3 terciles since the institution of ENCPAP system, ELBW infants who were started on ENCPAP but intubated within 1 week (CPAP failure) decreased over time (38.5% vs 13.8% vs 7.4%). There were other trends that did not reach significance, such as increased incidence of necrotizing enterocolitis (NEC). In a multivariate analysis controlling for gestational age, birth weight, and sepsis, the incidence of BPD was significantly lower over time (regression coefficient = −1.002 ± 0.375). Conclusions. The frequency of use of ENCPAP in ELBW infants and its success improved in our unit over time. The major positive association in this population was a reduction in BPD rates and an increase in average weight gain. Relation of ENCPAP and NEC should be evaluated further.

Is It Safer to Intubate Premature Infants in the Delivery Room

Objectives. Early nasal continuous positive airway pressure (ENCPAP) has recently emerged in neonatal units as an acceptable alternative to routine intubation and mandatory ventilation. The risks and benefits of ENCPAP have yet to be established. In this study, we aimed to examine variables that influenced the decision to initiate ENCPAP in the delivery room (DR). We also explored potential harmful effects of early intubation and examined whether unsuccessful ENCPAP attempts might subject infants to any unforeseen morbidity. Methods. All inborn very low birth weight (VLBW) infants admitted to the NICU since the implementation of the ENCPAP policy were included in this retrospective study. Infants were stratified initially into 2 cohorts according to whether they were intubated in the DR or began ENCPAP. Infants were then stratified into 4 groups according to the respiratory management during their first week of life. Infants in group 1 were supported with ENCPAP in the DR and continued to receive continuous positive airway pressure (CPAP) at least for the entire first week. Infants in group 2 began ENCPAP treatment in the DR but required intubation during the first week of life. Infants in group 3 were intubated in the DR but transitioned successfully to CPAP within the first 48 hours and were treated with CPAP for the first week of life or longer. Infants in group 4 were intubated in the DR and treated with intermittent mandatory ventilation for >48 hours. Univariate analyses compared different groups with the Wilcoxon nonparametric test, Kruskal-Wallis test, and analysis of variance. A multivariate regression model adjusted for differences in birth weights (BWs), gestational ages (GAs), race, and Apgar scores between the groups. Results. A total of 234 VLBW infants (weight of <1500 g) were admitted to the NICU during the period from August 1997 to December 2003. The mean BW was 977.1 ± 305.8 g, and the mean GA was 27.7 ± 2.7 weeks. The overall mortality rate was 11.1%, and the incidence of bronchopulmonary dysplasia among survivors was 17.4%. ENCPAP was implemented successfully in the DR for 151 (64.5%) infants, whereas 83 (35.5%) infants required intubation. Infants who required intubation had significantly lower GAs, BWs, and 1-minute Apgar scores. The use of ENCPAP in the DR increased significantly over time. The chance of successful maintenance with ENCPAP for >48 hours was not demonstrable at <24 weeks of gestation (10% success). Use of ENCPAP improved significantly by 25 weeks of gestation (45% success). Infants in group 1 required a shorter duration of oxygen use than did infants in group 3 (7.9 ± 18.3 vs 39 ± 32.7 days; regression coefficient [b] = 19 ± 5.3). None of the infants in group 1 developed intraventricular hemorrhage of grade III or IV or retinopathy of prematurity of stage 3 or 4. Infants in group 3 did not show improved outcomes, compared with group 1. Compared with group 4, infants in group 2 had a higher incidence of necrotizing enterocolitis (15.6% vs 7.3%; b = 2.5 ± 1.2). Conclusions. The success of ENCPAP improved with increased GA and with staff experience over time. Infants treated successfully with ENCPAP were unlikely to develop intraventricular hemorrhage of grade III or IV. Infants who experienced ENCPAP failure were at increased risk for the development of necrotizing enterocolitis. Infants who were intubated briefly in the DR were at increased risk for prolonged oxygen requirement. An individualized approach should be considered for respiratory support of VLBW infants.

Early weaning from CPAP to high flow nasal cannula in preterm infants is associated with prolonged oxygen requirement: A randomized controlled trial

OBJECTIVE To determine the better approach for weaning preterm infants from nasal continuous positive airway pressure (NCPAP) with or without transitioning to nasal cannula (NC). DESIGN/METHODS This is a randomized, open label, controlled trial. Preterm infants born at ≥28 weeks gestation who were clinically stable on NCPAP of 5 cm H(2)O with FiO(2)<0.30 for at least 24 h were randomly assigned to one of 2 groups. The no-NC group were kept on NCPAP until they were on FiO(2)=0.21 for 24 h, and then were weaned off NCPAP completely without any exposure to NC. If they met failing criteria, NCPAP was re-instituted. The NC-group was weaned off NCPAP when FiO(2) was ≤0.30 to NC (2 L/min) followed by gradual weaning from oxygen. Infants who failed NC were supported back with NCPAP for 24 h before making a second attempt of NC. RESULTS Sixty neonates were enrolled; 30 in each group. The two groups were similar in birthweight, gestational age, sex, antenatal steroids, mode of delivery, use of surfactant and xanthines, and duration of mechanical ventilation. After randomization, the no-NC group had fewer days on oxygen [median (interquartile range): 5 (1-8) vs 14 (7.5-19.25) days, p<0.001] and shorter duration of respiratory support [10.5 (4-21) vs 18 (11.5-29) days, p=0.03]. There were no differences between groups regarding success of weaning from NCPAP. CONCLUSIONS Weaning preterm infants from NCPAP to NC is associated with increased exposure to oxygen and longer duration of respiratory support.

Randomized, Controlled Trial on Tracheal Colonization of Ventilated Infants: Can Gravity Prevent Ventilator-Associated Pneumonia?

OBJECTIVE. The goal was to test the hypothesis that intubated infants positioned on their sides would be less likely to contract bacterial colonization in their tracheae, compared with those positioned supine. METHODS. We conducted a prospective, randomized, controlled trial with 60 intubated infants; 30 infants were positioned supine (supine group), and 30 infants were maintained in the lateral position (lateral group). Tracheal aspirates were cultured and bacterial colony counts were recorded after 48 hours and after 5 days of mechanical ventilation. RESULTS. After 2 days, the numbers of positive tracheal cultures in the supine group (67%) and in the lateral group (47%) showed no statistical difference. After 5 days of mechanical ventilation, tracheal cultures differed significantly between groups. Cultures were positive for 26 infants (87%) in the supine group and 9 infants (30%) in the lateral group. Compared with the lateral group, more infants in the supine group experienced increased colony counts or had new organisms in their tracheal aspirates over time (21 vs 8 infants). The most common organisms isolated from tracheal aspirates in both groups were Gram-negative rods. CONCLUSIONS. Respiratory contamination is very common among ventilated infants. Therefore, judicious use of mechanical ventilation cannot be overemphasized. Gravitational force can ameliorate the onset of respiratory colonization. The mechanism and clinical applicability of such observations need to be explored further.

Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study

Objective:Melatonin has been shown to be neuroprotective in animal models. The objective of this study is to examine the effect of melatonin on clinical, biochemical, neurophysiological and radiological outcomes of neonates with hypoxic–ischemic encephalopathy (HIE).Study Design:We conducted a prospective trial on 45 newborns, 30 with HIE and 15 healthy controls. HIE infants were randomized into: hypothermia group (N=15; received 72-h whole-body cooling) and melatonin/hypothermia group (N=15; received hypothermia and five daily enteral doses of melatonin 10 mg kg−1). Serum melatonin, plasma superoxide dismutase (SOD) and serum nitric oxide (NO) were measured at enrollment for all infants (N=45) and at 5 days for the HIE groups (N=30). In addition to electroencephalography (EEG) at enrollment, all surviving HIE infants were studied with brain magnetic resonance imaging (MRI) and repeated EEG at 2 weeks of life. Neurologic evaluations and Denver Developmental Screening Test II were performed at 6 months.Result:Compared with healthy neonates, the two HIE groups had increased melatonin, SOD and NO. At enrollment, the two HIE groups did not differ in clinical, laboratory or EEG findings. At 5 days, the melatonin/hypothermia group had greater increase in melatonin (P<0.001) and decline in NO (P<0.001), but less decline in SOD (P=0.004). The melatonin/hypothermia group had fewer seizures on follow-up EEG and less white matter abnormalities on MRI. At 6 months, the melatonin/hypothermia group had improved survival without neurological or developmental abnormalities (P<0.001).Conclusion:Early administration of melatonin to asphyxiated term neonates is feasible and may ameliorate brain injury.

Transport of premature infants is associated with increased risk for intraventricular haemorrhage

Background Intraventricular haemorrhages (IVH) greatly impact the outcome of very low birth weight (VLBW) infants. This study examines the correlation between inter-hospital transport and the incidence and severity of IVH in VLBW infants in a large cohort of data. Methods The US National Inpatient Sample Database (NIS) and its KID subportion were analysed for the years 1997–2004. Infants <1500 g were included in the study and were classified into transport and inborn groups. Groups were further classified according to birth weight into <1000 g and 1000–1499 g. IVH and severe IVH (grades 3–4) were compared between groups and subgroups. Adjusted OR for IVH or severe IVH in correlation with inter-hospital transport were calculated using logistic regression models while controlling for clinical and demographic confounders. We examined changing trends of the incidence of IVH, incidence of neonatal transport and OR for IVH in correlation with neonatal transport in VLBW infants over the years. Results A total of 67 596 VLBW infants were included in the study. Overall incidence of IVH in the sample was 14.7%; the transport group had more IVH compared to inborn group (27.4% vs 13.42%): adjusted OR 1.75 (95% CI 1.64 to 1.86; p<0.001). Severe IVH was higher in the transport group compared to the inborn group (44.1% vs 32.9%); adjusted OR 1.44 (95% CI 1.22 to 1.70, p=0.001). Similar results were demonstrated in weight-based subgroups. There was increasing trends for neonatal transport and for IVH over the years (p<0.001 for both) with no significant change in the OR for IVH in transported infants. Conclusion Inter-hospital transport of VLBW Infants is correlated with increased incidence and severity of IVH. This correlation has remained constant over the recent years.

Massage with kinesthetic stimulation improves weight gain in preterm infants

Objective:The aim of this study was to evaluate the effects of massage with or without kinesthetic stimulation on weight gain and length of hospital stay in the preterm infant.Study Design:A prospective randomized clinical trial was conducted evaluating the effects of massage with or without kinesthetic stimulation (KS) on weight gain and length of stay (LOS) in medically stable premature (<1500 g and/or ⩽32 weeks gestational age) neonates. Infants were randomized either to receive no intervention (control), massage therapy alone (massage), or massage therapy with KS (M/KS). Linear regression analysis was performed to evaluate differences in the primary outcomes between the groups after controlling for covariates. Post hoc analysis with stratification by birthweight (BW> and <1000 g) was also performed.Result:A total of 60 premature infants were recruited for this study; 20 infants in each group. Average daily weight gain and LOS were similar between the groups after controlling for covariates. For infants with BW>1000 g, average daily weight gain was increased in the intervention groups compared to control. This effect was mainly attributable to the M/KS group.Conclusion:Massage with KS is a relatively simple and inexpensive intervention that can improve weight gain in selected preterm infants. Length of hospital stay is not impacted by massage with or without KS. Further studies are needed to evaluate the effect of massage in the extremely low BW(<1000 g) infant.