Less invasive ventilation in extremely low birth weight infants from 1997 to 2011: survey versus evidence.

UNLABELLED Evidence for target values of arterial oxygen saturation (SaO2), CO2, and pH has changed substantially over the last 20 years. A representative survey concerning treatment strategies in extremely low-birth-weight infants (ELBW) was sent to all German neonatal intensive care units (NICUs) treating ELBW infants in 1997. A follow-up survey was conducted in 2011 and sent to all NICUs in Germany, Austria, and Switzerland. During the observation period, NICUs targeting SaO2 of 80, 85, and 90 % have increased, while units aiming for 94 and 96 % decreased (all p < 0.001). Similarly, NICUs aiming for pH 7.25 or lower increased, while 7.35 or higher decreased (both p < 0.001). Furthermore, more units targeted a CO2 of 50 mmHg (7.3 kPa) or higher (p < 0.001), while fewer targeted 40 or 35 mmHg (p < 0.001). Non-invasive ventilation (NIV) was used in 80.2 % of NICUs in 2011. The most frequently used ventilation modes were synchronized intermittent mandatory ventilation (SIMV) (67.5 %) and intermittent positive pressure ventilation (IPPV) (59.7 %) in 1997 and SIMV (77.2 %) and synchronized intermittent positive pressure ventilation (SIPPV) (26.8 %) in 2011. NICUs reporting frequent or always use of IPPV decreased to 11.0 % (p < 0.001). SIMV (77.2 %) and SIPPV (26.8 %) did not change from 1997 to 2011, while high-frequency oscillation (HFO) increased from 9.1 to 19.7 % (p = 0.018). Differences between countries, level of care, and size of the NICU were minimal. CONCLUSIONS Target values for SaO2 decreased, while CO2 and pH increased significantly during the observation period. Current values largely reflect available evidence at time of the surveys. WHAT IS KNOWN • Evidence concerning target values of oxygen saturation, CO 2 , and pH in extremely low-birth-weight infants has grown substantially. • It is not known to which extent this knowledge is transferred into clinical practice and if treatment strategies have changed. WHAT IS NEW • Target values for oxygen saturation in ELBW infants decreased between 1997 and 2011 while target values for CO 2 and pH increased. • Similar treatment strategies existed in different countries, hospitals of different size, or university versus nonuniversity hospitals in 2011.

Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants (EpoRepair).

BACKGROUND Preterm infants suffering from intraventricular hemorrhage (IVH) are at increased risk for neurodevelopmental impairment. Observational data suggest that recombinant human erythropoietin (rEPO) improves long-term cognitive outcome in infants with IVH. Recent studies revealed a beneficial effect of early high-dose rEPO on white matter development in preterm infants determined by magnetic resonance imaging (MRI). OBJECTIVES To summarize the current evidence and to delineate the study protocol of the EpoRepair trial (Erythropoietin for the Repair of Cerebral Injury in Very Preterm Infants). METHODS The study involves a review of the literature and the design of a double-blind, placebo-controlled, multicenter trial of repetitive high-dose rEPO administration, enrolling 120 very preterm infants with moderate-to-severe IVH diagnosed by cranial ultrasound in the first days of life, qualitative and quantitative MRI at term-equivalent age and long-term neurodevelopmental follow-up until 5 years of age. RESULTS AND CONCLUSIONS The hypothesis generated by observational data that rEPO may improve long-term cognitive outcomes of preterm infants suffering from IVH are to be confirmed or refuted by the randomized controlled trial, EpoRepair.

False normal Lung Clearance Index in infants with cystic fibrosis due to software algorithms.

BACKGROUND Lung clearance index (LCI), a marker of ventilation inhomogeneity, is elevated early in children with cystic fibrosis (CF). However, in infants with CF, LCI values are found to be normal, although structural lung abnormalities are often detectable. We hypothesized that this discrepancy is due to inadequate algorithms of the available software package. AIM Our aim was to challenge the validity of these software algorithms. METHODS We compared multiple breath washout (MBW) results of current software algorithms (automatic modus) to refined algorithms (manual modus) in 17 asymptomatic infants with CF, and 24 matched healthy term-born infants. The main difference between these two analysis methods lies in the calculation of the molar mass differences that the system uses to define the completion of the measurement. RESULTS In infants with CF the refined manual modus revealed clearly elevated LCI above 9 in 8 out of 35 measurements (23%), all showing LCI values below 8.3 using the automatic modus (paired t-test comparing the means, P < 0.001). Healthy infants showed normal LCI values using both analysis methods (n = 47, paired t-test, P = 0.79). The most relevant reason for false normal LCI values in infants with CF using the automatic modus was the incorrect recognition of the end-of-test too early during the washout. CONCLUSION We recommend the use of the manual modus for the analysis of MBW outcomes in infants in order to obtain more accurate results. This will allow appropriate use of infant lung function results for clinical and scientific purposes.

Accuracy of tidal breathing measurement of FloRight compared to an ultrasonic flowmeter in infants.

INTRODUCTION Monitoring breathing pattern is especially relevant in infants with lung disease. Recently, a vest-based inductive plethysmograph system (FloRight®) has been developed for tidal breathing measurement in infants. We investigated the accuracy of tidal breathing flow volume loop (TBFVL) measurements in healthy term-born infants and infants with lung disease by the vest-based system in comparison to an ultrasonic flowmeter (USFM) with a face mask. We also investigated whether the system discriminates between healthy infants and those with lung disease. METHODS Floright® measures changes in thoracoabdominal volume during tidal breathing through magnetic field changes generated by current-carrying conductor coils in an elastic vest. Simultaneous TBFVL measurements by the vest-based system and the USFM were performed at 44 weeks corrected postmenstrual age during quiet unsedated sleep. TBFVL parameters derived by both techniques and within both groups were compared. RESULTS We included 19 healthy infants and 18 infants with lung disease. Tidal volume per body weight derived by the vest-based system was significantly lower with a mean difference (95% CI) of -1.33 ml/kg (-1.73; -0.92), P < 0.001. Respiratory rate and ratio of time to peak tidal expiratory flow over total expiratory time (tPTEF/tE) did not differ between the two techniques. Both systems were able to discriminate between healthy infants and those with lung disease using tPTEF/tE. CONCLUSION FloRight® accurately measures time indices and may discriminate between healthy infants and those with lung disease, but demonstrates differences in tidal volume measurements. It may be better suited to monitor breathing pattern than for TBFVL measurements.

Rhinovirus Infections and Associated Respiratory Morbidity in Infants: A Prospective Cohort Study.

BACKGROUND Risk factors promoting rhinovirus (RV) infections are inadequately described in healthy populations, especially infants. OBJECTIVES To determine the frequency of symptomatic and asymptomatic RV infections and identify possible risk factors from host and environment among otherwise healthy infants. METHODS In a prospective birth cohort, respiratory health was assessed in 41 term-born infants by weekly telephone interviews during the first year of life, and weekly nasal swabs were collected to determine RV prevalence. In a multilevel logistic regression model, associations between prevalence and respiratory symptoms during RV infections and host/environmental factors were determined. RESULTS 27% of nasal swabs in 41 infants tested positive for RVs. Risk factors for RV prevalence were autumn months (OR=1.71, p=0.01, 95% CI 1.13-2.61), outdoor temperatures between 5-10 °C (OR=2.33, p=0.001, 95% CI 1.41-3.86), older siblings (OR=2.60, p=0.001, 95% CI 1.50-4.51) and childcare attendance (OR=1.53, p=0.07, 95% CI 0.96-2.44). 51% of RV-positive samples were asymptomatic. Respiratory symptoms during RV infections were less likely during the first three months of life (OR=0.34, p=0.003, 95% CI 0.17-0.69) and in infants with atopic mothers (OR=0.44, p=0.008, 95% CI 0.24-0.80). Increased tidal volume (OR=1.67, p=0.03, 95% CI 1.04-2.68) and outdoor temperatures between 2-5 °C (OR=2.79, p=0.02, 95% CI 1.17-6.61) were associated with more symptoms. CONCLUSIONS RVs are highly prevalent during the first year of life, and most infections are asymptomatic. Frequency of RV infections is associated with environmental factors, while respiratory symptoms during RV infections are linked to host determinants like infant age, maternal atopy, or premorbid lung function.

Barriers to Influenza Immunization: The Role of Physician Training on Influenza Vaccine Utilization in Six to Twenty-Three Month Old Infants

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Clinical decisions related to CBC screening of asymptomatic full-term infants at risk for group B streptococcus disease

Objective. Although complete blood count (CBC) changes occur with the development of clinical sepsis in newborns, the CBC has not been reported to be a sensitive predictor of sepsis in asymptomatic full-term newborn infants, nor has it been reported to be related to risk factors for sepsis or clinical decisions. The objective of this study was to evaluate the relationship between the WBC/I:T (immature:total neutrophil) ratio and maternal group B streptococcal (GBS) risk factors (rupture of membranes ≥18 hours, maternal temperature ≥100.4°F, maternal age ≤20 years, previous infant with invasive GBS disease, maternal GBS bacteriuria, and black ethnicity); and to evaluate the relationship between the WBC/I:T ratios and providers' clinical decisions (observe versus repeat the CBC or complete sepsis evaluation) in the asymptomatic full-term newborn at risk for early-onset GBS sepsis. ^ Methods. Medical records of infants admitted to the well baby nursery at a tertiary care teaching hospital in Houston, TX between 1/1/99 and 12/31/00 whose gestational ages were ≥35 weeks; who had mothers with GBS positive or unknown culture status and inadequate intrapartum antibiotic prophylaxis; and who had screening CBCs performed in the first 30 hours of life because of GBS risk were reviewed (n = 412). Demographic information, maternal GBS risk factors, CBC results, clinical decisions, and rationales for clinical decisions were collected. ^ Results. With the exception of black ethnicity (p = .0000, odds ratio = 0.213), no statistically significant differences in risk factors between infants with normal and abnormal WBC counts or normal and abnormal I:T ratios were found. Infants with abnormal WBCs had a significantly higher likelihood of having a CBC repeated (p = 0.002 for WBC). Providers documented the CBC result in the rationale for clinical decisions in 62% of the cases. ^ Conclusion. The CBC results were not related to maternal risk factors for GBS except for ethnicity. Black infants had significantly lower WBC levels than infants of other ethnicities, although this difference was clinically insignificant. Infants with abnormal WBCs had a significantly higher likelihood of undergoing repeat CBCs but not sepsis evaluations. Provider rationale was difficult to evaluate due to insufficient documentation. The screening CBC result did not impact the clinicians' decisions to initiate sepsis evaluations in this population. ^

Impact of maternal Tdap vaccination on pertussis infection in young infants

Undiagnosed infected mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention (CDC) recommends Tdap vaccine for post-partum women before hospital discharge. This intervention has been implemented at Ben Taub General Hospital (BTGH) in Houston, TX since January 2008. Our objective was to compare the proportion of infants born at BTGH and developing pertussis to the total number of pertussis cases before and after the intervention. Methods. We conducted a cross-sectional comparative study between the pre-intervention (7/2000 to 12/2007) and post-intervention (1/2008 to 5/2009) periods. Information on pertussis diagnosis was determined using ICD-9 codes, infection control records, and molecular microbiology reports from Texas Children's Hospital (TCH) and BTGH. Only patients ≤ 6 months of age with laboratory-confirmed B. pertussis infection were included in the study. Results. 481 infants had pertussis illness; 353 (73.3%) during pre-intervention and 128 (26.6%) during post-intervention years. The groups were comparable in all measures including age (median 73 vs. 62.5 days; p=0.08), gender (males 54.2%; p=0.47), length of hospitalization (median 9.8 vs. 4 9.5 days; p=0.5), outcomes (2 deaths in each period; p=0.28) and pertussis illness at TCH (95.2% vs. 95.3%; p=0.9). The proportion of pertussis patients born at BTGH, and thus amenable to protection by the intervention, was not statically different between the two periods after adjusting for age, gender and ethnicity (7.3% vs. 9.3%; an OR=1.05, 95% CI 0.5-2.1, p=0.88). Conclusions. Vaccinating only mothers with Tdap in the post-partum period does not reduce the proportion of pertussis in infants age ≤ 6 months. Efforts should be directed at Tdap immunization of not only mothers, but also all household and key contacts of newborns to protect them against pertussis illness before the primary DTaP series is completed.^

Probiotics and the prevention of necrotizing enterocolitis in preterm infants: A systematic review of the literature

Necrotizing enterocolitis is a common gastrointestinal disease associated with high mortality and morbidity among preterm infants. This was a systematic literature review that evaluated whether the administration of probiotic supplements is of benefit in the prevention of NEC. The search was narrowed to randomized clinical trials identified through The Cochrane Central Register of Controlled Trials, U.S. National Institute of Health clinical trials registry database, Pub Med and OVID MEDLINE databases. Inclusion criteria were: prospective, randomized clinical trials that administered probiotics as a preventive measure against NEC for infants of early gestational age (<35 wks) and/or low birth weight (<1500g), maintained NEC as the primary measured outcome, used Bell’s classification for NEC diagnosis with reports of stage 2 NEC or higher, and began probiotic administration within 10 days of life. Trials were excluded if participant enrollment was fewer than 100 infants, published before the year 2000, or probiotic supplementation was discontinued after less than seven consecutive days. Based on specific study characteristics, each resulting article was then judged by two authors for study quality. The search was further narrowed to studies of either high or moderate quality, which were then summarized in a set of tables based on study characteristics and results. From an initial set of 20 identified studies, five clinical trials met all criteria; each was discussed thoroughly based on trial limitations, strengths and comparisons to other included publications. Based on this review, the weight of evidence appears to support the use of probiotic supplementation in preterm infants as a preventive measure against NEC. Recommendations for future research were also provided.^

Targeted immunization to protect infants against pertussis in the United States

Pertussis is an infectious disease caused by the bacteria Bordetella pertussis, and is associated with a serious respiratory infection, a prolonged cough, and can require hospitalization. A vaccine for adolescents and adults has been available since 2005. This paper examines one recommended immunization strategy to prevent pertussis among infants, called “cocooning.” The strategy focuses on creating immunity among adult caregivers so they serve as a protective cocoon to the newborns, who are too young to be vaccinated. This paper looks at relevant studies summarizing implementation of cocooning strategies and addresses the question – Does the research literature support the view of using cocooning as an effective strategy to prevent pertussis in infants? After exclusions, 8 studies remained for synthesis. The evidence shows that cocooning is complex strategy and the evidence is mixed when it comes to ensuring an increase in immunization of caregivers. ^

Feeding practices and their associations with diarrhea incidence in a cohort of rural Egyptian infants

A study was conducted in 4 villages in Bilbeis, Egypt, to document the infant feeding practices and identify their determinants, and examine the associations between feeding practices and diarrhea incidence in infants. A cohort of 152 infants were followed from birth with twice-weekly home visits to record feeding practices and diarrheal illness. Cross-sectional information was obtained about child birth; early neonatal feeding practices; and the socioeconomic, demographic, and water and sanitation characteristics of study families.^ Prelacteal fees were given to 60% of the infants. Nineteen percent of the infants were wet nursed at least once during the first week of life. Breast-feeding prevalence declined from 100% among infants aged less than 12 weeks to 84% among those aged 44-47 weeks. The prevalence of exclusive breast-feeding among breast-fed infants was 38% in those aged less than 4 weeks, increased to 54% in age period 4-7 weeks, and then declined rapidly to 4% in age period 24-27 weeks. The patterns and determinants of consumption by breast-fed infants of specific supplements were examined in detail.^ Between birth and age 47 weeks, the diarrhea incidence rate per person-year among breast-fed infants (6.84 episodes) was identical to the rate among all infants (6.89 episodes). In age period 0-11 weeks, the diarrhea incidence rate among breast-fed infants receiving supplements was 1.3 times (95% confidence interval: 0.9-2.0) higher than the rate among those exclusively breast-fed. In other age periods, diarrhea incidence was generally nonsignificantly higher among exclusively breast-fed infants than among those partially breast-fed and those completely weaned.^ Both univariate and multivariate analyses were done to examine the associations between diarrhea incidence and the consumption by breast-fed infants of specific supplements. After multivariate adjustment, supplements that showed significant, borderline, or suggestive positive associations with diarrhea incidence were cereal-water, cheese, raw vegetables, and 'other' foods. Significant, borderline, or suggestive negative associations were observed between diarrhea incidence and the intake of fresh animal milk, and potatoes.^ To reduce the risk of diarrhea, indiscriminate use of supplements among Bilbeis infants aged less than 12 weeks should be strongly discouraged. While mothers in this area should be educated about methods of safer preparation, handling, storage, and administration of all weaning foods, their attention should be particularly drawn to the 4 foods that were found to be positively associated with diarrhea incidence among infants in this study. ^

Effects of breastfeeding and naturally acquired immunity on infection with {\it Giardia lamblia}: A study in a cohort of Mexican infants

Giardia lamblia is one of the most common causes of gastrointestinal tract infection among young children worldwide. Yet host protection against this parasite and the effect of infection with Giardia on infant growth are poorly understood. It was hypothesized that among young children, protection against infection with Giardia is afforded by breastfeeding and previous infection with the parasite and further, that infection with Giardia decreases growth velocity. From 4/88 to 4/90, 197 infants in a poor area of Mexico City were followed from 0 to 18 months of age, with stool specimens, symptoms and feeding status data collected weekly. A total of 6,031 stool specimens were tested for Giardia antigen by enzyme-linked immunosorbent assay. There were 1.0 Giardia infections per child-year; 25% were symptomatic and 54% lasted more than 1 month; 94 infants had 1, and 33 had 2 or more infections. Breastfeeding status was coded and analyzed for each child-week of follow up. 91% of study infants were breastfed from birth, 57% at 6 months and 38% at 12 months of age. Rate ratios for non-breastfeeding adjusted for confounding factors were calculated from stratified analyses and the Cox proportional hazards model. Not breastfeeding was a significant risk factor for first infection with Giardia vs. any breastfeeding (adjusted RR = 1.8; 1.1, 2.8) at all ages; a dose response was demonstrated by degree of breastfeeding. The adjusted rate ratio for non-breastfeeding vs. partial breastfeeding was 1.6 (1.03, 2.6) and for non-breastfeeding vs. complete breastfeeding was 4.7 (1.4, 15.9). Among Giardia infected infants, breastfeeding did not protect against diarrheal symptoms or shorten the duration of carriage. First and repeat infections with Giardia did not differ in duration or the percent symptomatic. The analysis of growth and Giardia infection was inconclusive but suggested that a history of Giardia infection might be associated with decreased weight velocity, while an immediate chronic infection might be associated with increased weight velocity. In summary, these data indicate that breastfeeding protects infants against infection with Giardia; provide no evidence of protection against repeat infections resulting from a prior infection and suggest but do not establish that a history of Giardia infection might be associated with decreased growth in young children. ^