Randomized controlled trial of restrictive fluid management in transient tachypnea of the newborn.

OBJECTIVE: To determine the effect of mild fluid restriction on the hospital course of neonates with transient tachypnea of the newborn (TTN). STUDY DESIGN: In this pilot prospective randomized controlled trial of 64 late preterm and term neonates diagnosed with TTN at a single tertiary care hospital in the United States, patients were randomized to receive standard fluid management or mild fluid restriction. The primary outcome was duration of respiratory support. Secondary outcomes were duration of admission to the intensive care unit, time to first enteral feed, and total and composite hospital costs. Results were analyzed by t-test, χ(2) test, Kaplan-Meier estimation, and proportional hazards regression. RESULTS: Fluid restriction did not cause adverse events or unsafe dehydration. Fluid management strategy did not affect primary or secondary outcomes in the total study population. Fluid restriction significantly reduced the duration of respiratory support (P = .008) and hospitalization costs (P = .017) in neonates with severe TTN. CONCLUSION: Mild fluid restriction appears to be safe in late preterm and term neonates with uncomplicated TTN. Fluid restriction may be of benefit in decreasing the duration of respiratory support and reducing hospitalization costs in term and late preterm neonates with uncomplicated severe TTN.

Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers.

Butyrate, one of the SCFA, promotes the development of the intestinal barrier. However, the molecular mechanisms underlying the butyrate regulation of the intestinal barrier are unknown. To test the hypothesis that the effect of butyrate on the intestinal barrier is mediated by the regulation of the assembly of tight junctions involving the activation of the AMP-activated protein kinase (AMPK), we determined the effect of butyrate on the intestinal barrier by measuring the transepithelial electrical resistance (TER) and inulin permeability in a Caco-2 cell monolayer model. We further used a calcium switch assay to study the assembly of epithelial tight junctions and determined the effect of butyrate on the assembly of epithelial tight junctions and AMPK activity. We demonstrated that the butyrate treatment increased AMPK activity and accelerated the assembly of tight junctions as shown by the reorganization of tight junction proteins, as well as the development of TER. AMPK activity was also upregulated by butyrate during calcium switch-induced tight junction assembly. Compound C, a specific AMPK inhibitor, inhibited the butyrate-induced activation of AMPK. The facilitating effect of butyrate on the increases in TER in standard culture media, as well as after calcium switch, was abolished by compound C. We conclude that butyrate enhances the intestinal barrier by regulating the assembly of tight junctions. This dynamic process is mediated by the activation of AMPK. These results suggest an intriguing link between SCFA and the intracellular energy sensor for the development of the intestinal barrier.

Bottle-feeding behaviors in preterm infants with and without bronchopulmonary dysplasia.

OBJECTIVE: This study compared bottle-feeding behaviors in preterm infants with and without bronchopulmonary dysplasia (BPD) during the initial hospitalization. METHOD: Individual sucking characteristics and feeding transitional rates were compared in 41 preterm infants (22 boys, 19 girls) with BPD and 99 infants (44 boys, 55 girls) without BPD. Observations of the first bottle feeding and observations of the last feeding before discharge were obtained from medical records of all infants retrospectively. RESULTS: On discharge, infants with BPD, unlike those without BPD, continued to have an immature sucking pattern and required longer hospital stays to attain full oral feeding (p < .001). No differences were found between the BPD and non-BPD groups in time needed for feeding and use of oral support. CONCLUSION: These results suggest that feeding transitional rate, rather than sucking pattern, may be a better discharge indicator for infants with BPD.

Acidosis in newborns with nuchal cords and normal Apgar scores.

OBJECTIVE: Apgar scores and cord blood gases (BG) and pH were compared between a group of babies with nuchal cords and a group without nuchal cords and uncomplicated deliveries. STUDY DESIGN: We collected umbilical arterial (UA) and umbilical venous (UV) blood samples from the placentas of term infants from both normal deliveries (NORM, n=29) and nuchal cords (NUCH, n=33). BG/pH and hematocrit were measured; base deficits and oxygen contents were calculated; and a member of the study assigned Apgar scores and demographic data were collected from the babies' charts. RESULTS: Median Apgar scores in the NUCH babies at 1 and 5 minutes were 9 and 9 respectively, which did not differ from the NORM infants. The pH, PCO(2), and oxygen content obtained from UV of the NUCH infants was not statistically different from the NORM. The pH and oxygen content of the NUCH UA was significantly lower than that of the NORM. The UA PCO(2) in the NUCH was greater than the NORM. Veno-arterial (VA) differences (Delta VA) in pH and PCO(2) of the NUCH infants were greater than that of the NORM. CONCLUSION: The Apgar score is not a sensitive indicator of acid-base changes in nuchal cord patients; UV samples alone may be misleading. UA must be sampled to detect the hypercapnia and diminished oxygen content that is a result of the nuchal cord.

Is there an advantage of using pressure support ventilation with volume guarantee in the initial management of premature infants with respiratory distress syndrome? A pilot study.

OBJECTIVE: To evaluate the feasibility of using the pressure support ventilation with volume guarantee (PSV-VG) as an initial ventilatory mode in preterm infants with respiratory distress syndrome (RDS) after surfactant treatment to achieve accelerated weaning of peak inspiratory pressure (PIP) and mean airway pressure (MAP). STUDY DESIGN: Initial 24-hour ventilatory parameters were compared in two groups of preterm infants managed by PSV-VG and the synchronized intermittent mandatory ventilation (SIMV) mode in a randomized controlled pilot study after surfactant treatment for RDS. A total of 16 babies were randomized to PSV-VG (1198+/-108 g [mean+/-SEM]; 27.9+/-0.6 weeks) and 18 babies to SIMV (birth weight 1055+/-77 g; gestational age 27.4+/-0.5 weeks). Repeated measures analysis of variance was used to compare serial values of PIP and MAP in the two groups. RESULTS: The PIP and MAP decreased over time (p<0.001) during the first 24 hours after surfactant administration in both groups but the decrease in MAP was faster in the SIMV group compared to PSV-VG group (p=0.035). The median numbers of blood gases during the first 24 hours were four and two in the SIMV and PSV-VG groups, respectively (p<0.001). The overall outcomes were not significantly different between the two groups. CONCLUSION: PSV-VG did not offer any ventilatory advantage over SIMV in the initial management of surfactant-treated premature newborns with RDS except for minimizing the number of blood gases.

Breastfeeding and delivery room neonatal collapse.

Sudden unexpected neonatal collapse in the delivery room is a rare occurrence in healthy term infants. Upper airway obstruction may occur from improper positioning of the newborn even while breastfeeding. Such occlusion may have dire consequences if not recognized immediately. We report 2 healthy term neonates who suffered respiratory arrest while in the mother's arms and attempting breastfeeding. In each case, rapid response by the delivery room nurse averted tragedy. Metabolic and infectious evaluations were unremarkable. Both babies have been well on subsequent examinations. We conclude that proper education of mothers and safe positioning of neonates is critical during the initiation of breastfeeding.

In utero pesticide exposure, maternal paraoxonase activity, and head circumference.

Although the use of pesticides in inner-city homes of the United States is of considerable magnitude, little is known about the potentially adverse health effects of such exposure. Recent animal data suggest that exposure to pesticides during pregnancy and early life may impair growth and neurodevelopment in the offspring. To investigate the relationship among prenatal pesticide exposure, paraoxonase (PON1) polymorphisms and enzyme activity, and infant growth and neurodevelopment, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. In this report we evaluate the effects of pesticide exposure on birth weight, length, head circumference, and gestational age among 404 births between May 1998 and May 2002. Pesticide exposure was assessed by a prenatal questionnaire administered to the mothers during the early third trimester as well as by analysis of maternal urinary pentachlorophenol levels and maternal metabolites of chlorpyrifos and pyrethroids. Neither the questionnaire data nor the pesticide metabolite levels were associated with any of the fetal growth indices or gestational age. However, when the level of maternal PON1 activity was taken into account, maternal levels of chlorpyrifos above the limit of detection coupled with low maternal PON1 activity were associated with a significant but small reduction in head circumference. In addition, maternal PON1 levels alone, but not PON1 genetic polymorphisms, were associated with reduced head size. Because small head size has been found to be predictive of subsequent cognitive ability, these data suggest that chlorpyrifos may have a detrimental effect on fetal neurodevelopment among mothers who exhibit low PON1 activity.

Meconium enhances the growth of perinatal bacterial pathogens.

OBJECTIVE: To demonstrate the effects of meconium on growth of bacterial pathogens, which are common causes of intra-amniotic infection and neonatal sepsis. METHODS: Meconium collected from 9 healthy neonates was suspended as a 20% solution using sterile saline. In experiment 1, separate test tubes of meconium solution and sterile saline (the control) were individually inoculated with 10(6) colony-forming units of a single species of the following test pathogens: Escherichia coli, Enterococcus faecalis, Group B Streptococcus, Staphylococcus aureus, Pseudomonas aeruginosa, and Listeria monocytogenes. After incubation at 37 degree C for 24 hours, 1 L each of the bacterial-meconium and bacterial-saline solutions was inoculated onto 5% sheep blood agar. After 24 hours of incubation, the number of developing colonies was counted. In experiment 2, equal volumes of meconium and saline solutions were inoculated with 10(5) colony-forming units of either E. coli or Group B Streptococcus. At intervals of 6, 9, and 24 hours post-incubation, 1 L each of the bacterial-meconium and bacterial-saline solutions was inoculated onto 5% sheep blood agar plates, and colonies were counted after overnight incubation. RESULTS: In the first experiment, 24 hours of incubation resulted in bacterial amplification in the meconium solution from an initial inoculum of 10(6) colony-forming units/mL to 10(9) colony-forming units/mL. In contrast, the same inoculation of saline solution (control) showed no increase in colony counts over the same time interval. For E. coli and Group B Streptococcus in experiment 2, growth enhancement in meconium was seen as early as 6 hours, as colony counts of a test species increased from 105 colony-forming units/mL to 10(9)-10(10) colony-forming units/mL. CONCLUSION: Enhanced growth of perinatal pathogens in meconium was constantly observed, and can occur as early as 6 hours after bacterial interaction of meconium.

Ontogeny and prenatal expression of trefoil factor 3/ITF in the human intestine.

BACKGROUND: Trefoil factor 3 (TFF3) or intestinal trefoil factor (ITF), a peptide normally expressed and secreted by goblet cells at the mucosal surface of the small intestine and colon, is important for the maintenance and repair of the intestinal mucosal barrier. AIM: To study the ontogeny and developmental expression of TFF3 in human intestine. SUBJECTS: We examined TFF3 expression in formalin-fixed and paraffin-embedded intestinal tissues from 24 fetuses (gestational age [GA] 12-23 weeks) and 5 adults by immunohistochemical staining. To determine whether TFF3 is excreted into the fetal intestinal tract, first-passed meconium samples were collected from 43 newborn infants (gestational age 24-41 weeks). The presence of TFF3 was examined by Western blot analysis and the relative levels of TFF3 in the meconium were quantified with a slot blot assay. RESULTS: TFF3 can be detected by immunohistochemistry in human intestine as early as 12 weeks gestation. TFF3 is present in the meconium of newborn infants; no significant difference exists in TFF3 levels in the meconium of premature infants with birth weight (BW) less than 1500 g compared to those with birth weight equal to or more than 1500 g. CONCLUSION: Premature infant's susceptibility to intestinal mucosal injury is unlikely to be explained by developmental expression of TFF3 in human intestine since secreted TFF3 is not deficient in premature infants.

Is the best interest standard good for pediatrics?

We argue that the "best interest standard" for surrogate decision-making is problematic for a number of reasons. First, reliance on the best interest standard is subjective. Second, it leads to behavior that is intolerant and polarizing. Third, appeals to the best interest standard are often vague and indeterminate. After all, cases are usually controversial precisely because reasonable people disagree about what is or is not in a child's best interest. We then recommend that, instead of the best interest standard, parents should be held to a standard that we call the "not unreasonable" standard. By that standard, parents' decisions would be respected unless they were deemed unreasonable. This recommendation would allow a greater range for parental discretion than the best interest standard.

Importance of birth weight as a risk factor for severe retinopathy of prematurity when gestational age is 30 or more weeks.

PURPOSE: To determine whether birth weight less than 1500 g is a relevant guideline indicating the need for examination for retinopathy of prematurity (ROP) when gestational age at birth is 30 or more completed weeks. DESIGN: A retrospective observational cohort study. METHODS: A total of 266 infants in a single institutional neonatal intensive care unit (NICU), whose gestational age at birth was 30 or more weeks but whose birth weight was less than 1500 g, were examined according to published guidelines. Infants with lethal congenital anomalies or major ocular abnormalities were excluded. Outcomes were vascularization in retinal zone III without a prior need for treatment, or ROP warranting treatment. RESULTS: A study outcome was reached by 212 infants. Two hundred and eleven (99.5%) became vascularized through zone III without needing treatment. Only 1 (0.5%) required treatment for ROP. The 95% confidence interval for the occurrence rate of ROP requiring treatment in this cohort was 0.01%-2.60%. CONCLUSION: Our results suggest that the occurrence rates of ROP requiring treatment in infants with gestational age 30 or more weeks and birth weight less than 1500 g is very low, and could indicate the need to revise examination guidelines for this subgroup of infants.

Antibiotic use in newborns with transient tachypnea of the newborn.

BACKGROUND: Initiation of empiric antibiotic treatment for possible early-onset sepsis is recommended for late preterm and term neonates with respiratory distress. There is no evidence base to this approach. OBJECTIVES: To determine the incidence of adverse infectious events in neonates with transient tachypnea of the newborn (TTN) managed with a risk-factor-based restrictive antibiotic use policy. METHODS: This is a single institution retrospective cohort study of neonates with primary diagnosis of TTN between 2004 and 2010. The relationship between antibiotic exposure and infectious outcomes during the neonatal hospitalization was evaluated. An infectious outcome was defined as pneumonia, bacteremia, clinical sepsis, or death. Analysis included t test, χ(2) test, and analysis of variance as appropriate. RESULTS: 745 neonates with TTN met inclusion criteria. None of the 494 antibiotic-naive infants, and 212 of the 251 antibiotic-exposed infants had identifiable risk factors for sepsis. No infectious outcomes occurred in infants who did not receive antibiotics. Eight neonates with TTN received full antibiotic treatment for early-onset sepsis. Each was appropriately identified for early receipt of antibiotics based on historical or clinical risk factors for early-onset sepsis. CONCLUSIONS: This study suggests that empiric postnatal antibiotic treatment may not be warranted for late preterm and term infants with TTN in the absence of specific infectious risk factors.

Group B Streptococcus exposure and self-limited respiratory distress in late preterm and term neonates.

BACKGROUND: Self-limited respiratory distress is a common neonatal respiratory morbidity for which effective treatments are lacking. Supportive care with non-invasive respiratory support is the norm. Animal models suggest that intrapartum exposure to group B Streptococcus (GBS) may cause mild pulmonary hypertension in the neonate, resulting in self-resolving respiratory distress. Treatments for pulmonary hypertension are currently not provided to neonates with self-limited respiratory distress empirically. OBJECTIVES: This study examines the hypothesis that the incidence and severity of self-limited respiratory distress are altered by intrapartum exposure to GBS and antibiotic prophylaxis (IAP) in a human population. METHODS: This is a 10-year single-center cohort study of retrospective data of late preterm and term neonates diagnosed with self-limited respiratory distress. Multiple logistic models were fitted to examine associations between exposure to GBS and IAP, and markers of self-limited respiratory distress severity. Additional linear regression models were fitted to examine the association between exposure to GBS and IAP, and duration of respiratory support for self-limited respiratory distress. Finally, crude and gestational age-adjusted incidence of self-limited respiratory distress among GBS-exposed and -unexposed infants, as well as the odds of self-limited respiratory distress based on GBS exposure were calculated. RESULTS: 584 neonates met study criteria. Neither GBS exposure nor IAP exposure was associated with severity of self-limited respiratory distress in multiple models. Crude and adjusted incidence of self-limited respiratory distress among neonates did not differ by GBS exposure history. CONCLUSIONS: Although animal studies indicate that GBS-mediated pulmonary hypertension may contribute to self-limited respiratory distress, neither exposure to GBS nor IAP was associated with an increased severity or incidence of self-limited respiratory distress in our human study population. Treatments for pulmonary hypertension are unlikely to speed symptom resolution for patients with self-limited respiratory distress.

Distribution dynamics of recombinant Lactobacillus in the gastrointestinal tract of neonatal rats.

One approach to deliver therapeutic agents, especially proteins, to the gastro-intestinal (GI) tract is to use commensal bacteria as a carrier. Genus Lactobacillus is an attractive candidate for use in this approach. However, a system for expressing exogenous proteins at a high level has been lacking in Lactobacillus. Moreover, it will be necessary to introduce the recombinant Lactobacillus into the GI tract, ideally by oral administration. Whether orally administered Lactobacillus can reach and reside in the GI tract has not been explored in neonates. In this study, we have examined these issues in neonatal rats. To achieve a high level of protein expression in Lactobacillus, we tested the impact of three promoters and two backbones on protein expression levels using mRFP1, a red fluorescent protein, as a reporter. We found that a combination of an L-lactate dehydrogenase (ldhL) promoter of Lactobacillus sakei with a backbone from pLEM415 yielded the highest level of reporter expression. When this construct was used to transform Lactobacillus casei, Lactobacillus delbrueckii and Lactobacillus acidophilus, high levels of mRFP1 were detected in all these species and colonies of transformed Lactobacillus appeared pink under visible light. To test whether orally administered Lactobacillus can be retained in the GI tract of neonates, we fed the recombinant Lactobacillus casei to neonatal rats. We found that about 3% of the bacteria were retained in the GI tract of the rats at 24 h after oral feeding with more recombinant Lactobacillus in the stomach and small intestine than in the cecum and colon. No mortality was observed throughout this study with Lactobacillus. In contrast, all neonatal rats died within 24 hours after fed with transformed E. coli. Taken together, our results indicate that Lactobacillus has the potential to be used as a vehicle for the delivery of therapeutic agents to neonates.

Endotracheal tube: friend or foe? Bacteria, the endotracheal tube, and the impact of colonization and infection.

The microbiology of the endotracheal tube culture plays a role in diagnosing a variety of diseases in the newborn intensive care unit, including subglottic stenosis, bronchopulmonary dysplasia, and ventilator-associated pneumonia. Bacterial production of a biofilm that coats the endotracheal tube acts as a reservoir for infection, prevents eradication, and may play a role in the development of subglottic stenosis. The diagnosis of ventilator-associated pneumonia is limited by the CDC definition as well as currently available diagnostic methods. Biomarkers could aid in differentiating colonization from infection, but are not available to most clinicians. The etiology of ventilator-associated pneumonia is often polymicrobial. Failure to differentiate colonization from infection results in unnecessary prescription of antibiotics, which could contribute to antimicrobial resistance. Measures to prevent ventilator-associated pneumonia have been described, primarily in the adult population.

Statewide NICU central-line-associated bloodstream infection rates decline after bundles and checklists.

OBJECTIVE: In 2008, all 18 regional referral NICUs in New York state adopted central-line insertion and maintenance bundles and agreed to use checklists to monitor maintenance-bundle adherence and report checklist use. We sought to confirm whether adopting standardized bundles and using central-line maintenance checklists reduced central-line-associated bloodstream infections (CLABSI). METHODS: This was a prospective cohort study that enrolled all neonates with a central line who were hospitalized in any of 18 NICUs. Each NICU reported CLABSI and central-line utilization data and checklist use. We used χ(2) to compare CLABSI rates in the preintervention (January to December 2007) versus the postintervention (March to December 2009) periods and Poisson regression to model adjusted CLABSI rates. RESULTS: Each study period included more than 55 000 central-line days and more than 200 000 patient-days. CLABSI rates decreased 67% statewide (risk ratio: 0.33 [95% confidence interval: 0.27-0.41]; P < .0005); after adjusting for the altered central-line-associated bloodstream infection definition in 2008, by 40% (risk ratio: 0.60 [95% confidence interval: 0.48-0.75]; P < .0005). A total of 13 of 18 NICUs reported using maintenance checklists for 10% to 100% of central-line days. The checklist-use rate was associated with the CLABSI rate (coefficient: -0.57, P = .04). A total of 10 of 18 NICUs were independent CLABSI rate predictors, ranging from 1 site with greatly reduced risk (incidence rate ratio: 0.04, P < .0005) to 1 site with greatly increased risk (incidence rate ratio: 2.87, P < .0005). CONCLUSIONS: Although standardizing central-line care elements led to a significant statewide decline in NICU CLABSIs, site of care remains an independent risk factor. Using maintenance checklists reduced CLABSIs.