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.

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.

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.

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.

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.

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.

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.

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.

Multiple factors related to bottle-feeding performance in preterm infants.

BACKGROUND: A great deal of attention has focused on understanding preterm infant feeding behaviors and on strategies to support the preterm infant during this period; however, comprehensive descriptions of the feeding behavior of preterm infants that incorporate an examination of multiple subsystem levels are lacking. OBJECTIVE: To examine various physical indicators related to preterm infants' bottle-feeding performance. METHODS: This was a retrospective, descriptive, exploratory study using a convenience sample. Medical records of 116 preterm infants were reviewed from the initiation of bottle-feeding until discharge from the neonatal intensive care unit. This study examined bottle-feeding performance (volume intake in milliliters per minute) as well as postmenstrual age, weight at each observed feed, oral motor skills, signs of distress, feeding techniques, feeding experience, gender, and Apgar scores at 5 minutes. Oral motor skills were measured by the Neonatal Oral Motor Assessment Scale. RESULTS: Linear mixed-effects models were used to examine the relationship between bottle-feeding performance and the remaining variables. Postmenstrual age, weight at each observed feed, oral motor skills, feeding experience, and feeding techniques were found to be significant predictors of feeding performance at the .05 level. CONCLUSIONS: Multiple factors, both intrinsic and extrinsic, play a role in determining an infant's bottle-feeding performance. In addition to age and weight, the presently employed conventional criteria, oral motor skills, feeding practice, and feeding techniques also contribute to infants' feeding performance. Arbitrary age (34 weeks gestational age) and weight criteria (1,500 g) should not be the only indicators for oral feeding.

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.

Necrotising enterocolitis: the state of the science.

Necrotizing enterocolitis is the most common gastrointestinal emergency of the neonate, affecting 5-10% of infants, yet the pathogenesis remains unclear. Widely accepted risk factors include prematurity, enteral feeds, bacterial colonization and mucosal injury. How these or other yet identified factors come together to create the classic clinical and pathologic features is the subject of much research. The activation of the cytokine cascade, in part by bacterial ligands, appears to play a key role in mucosal injury. Two mediators that may also contribute are platelet activating factor and intestinal toll-like receptors. Short chain fatty acids, the products of bacterial fermentation of carbohydrates, have been thought to cause mucosal injury. Overgrowth of pathogenic bacteria in the face of a decreased commensal population may play a key role. A current focus of clinical research involves probiotics, enterally fed forms of commsenal bacteria. This may set the stage for a healthier intestinal ecosystem and possibly, decreased risk of NEC.

Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer model of intestinal barrier.

Production of short-chain fatty acids (SCFA) in the intestinal lumen may play an important role in the maintenance of the intestinal barrier. However, overproduction/accumulation of SCFA in the bowel may be toxic to the intestinal mucosa and has been hypothesized to play a role in the pathogenesis of neonatal necrotizing enterocolitis (NEC). By using a Caco-2 cell monolayer model of intestinal barrier, we report here that the effect of butyrate on the intestinal barrier is paradoxical. Butyrate at a low concentration (2 mM) promotes intestinal barrier function as measured by a significant increase in transepithelial electrical resistance (TER) and a significant decrease in inulin permeability. Butyrate at a high concentration (8 mM) reduces TER and increases inulin permeability significantly. Butyrate induces apoptosis and reduces the number of viable Caco-2 cells in a dose-dependent manner. Intestinal barrier function impairment induced by high concentrations of butyrate is most likely related to butyrate-induced cytotoxicity due to apoptosis. We conclude that the effect of butyrate on the intestinal barrier is paradoxical; i.e. whereas low concentrations of butyrate may be beneficial in promoting intestinal barrier function, excessive butyrate may induce severe intestinal epithelial cell apoptosis and disrupt intestinal barrier.

Short-chain fatty acid induces intestinal mucosal injury in newborn rats and down-regulates intestinal trefoil factor gene expression in vivo and in vitro.

BACKGROUND: Luminal administration of short-chain fatty acids (SCFAs) induces dose-dependent intestinal mucosal injury in newborn rats. However, the mechanism underlying the injurious effects of SCFAs on intestinal mucosa in neonates is unclear. Intestinal trefoil factor (ITF) is a factor important for the maintenance and repair of the intestinal mucosal barrier. Regulation of ITF gene expression by SCFAs may be involved as one of the mechanisms. OBJECTIVES: To examine the effect of butyrate-induced colonic injury on ITF gene expression in vivo and to determine the molecular mechanisms underlying the butyrate regulation of ITF gene expression in vitro. METHODS: Whole-section colonic tissues from 9- to 10-day-old Sprague-Dawley rats that have received butyric acid at two different concentrations (150 mmol/L and 300 mmol/L) and for different time periods were processed for total RNA extraction and Northern blot analysis. Littermates that received normal saline or lactic acid at 300 mmol/L served as controls. The effect of butyrate on ITF gene expression was also examined in vitro with human colonic epithelial LS 174T cells. To further define ITF gene regulation by butyrate, transient transfection assays were performed on a 930 bp human ITF promoter-luciferase reporter gene plasmid in LS174T cells with or without the presence of butyrate. RESULTS: Concurrent with mucosal injury, butyric acid inhibited ITF gene expression in colonic tissues of newborn rats as well as in intestinal epithelial cells in a dose- and time-dependent manner. Furthermore, butyrate reduced ITF promoter report gene activity in transfected LS174T cell, suggesting that butyric acid regulation of ITF gene is by way of a specific ITF promoter. CONCLUSIONS: Butyric acid induced-intestinal mucosal injury in newborn rats is associated with down-regulation of ITF gene expression. The changes in ITF gene expression in vivo may play a role in the pathogenesis of SCFA-induced intestinal mucosal injury.

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.

Short-chain fatty acids induce colonic mucosal injury in rats with various postnatal ages.

Short chain fatty acids (SCFAs) may play a role in the pathogenesis of neonatal necrotizing enterocolitis. To evaluate the injurious effect of SCFAs on the colonic mucosa of rats at various postnatal developmental stages, we studied a total of 170 newborn Sprague-Dawley rats at postnatal ages days 3, 9, and 23. A 1.8-F silastic catheter or umbilical catheter was inserted rectally deep into the proximal colon of the rats. Rats from each of the three postnatal age groups were randomly divided to receive one of the following distinct SCFA solutions: acetic acid, butyric acid, propionic acid, or a mixture of above SCFAs solutions. An additional subgroup of rats from each of the age groups received normal saline as a control. The concentration of each SCFA solution was 300 mM, and the pH of all solutions was adjusted to 4.0. The volume of administered solution was 0.1 mL/10 g of body weight. After 24 h, all rats were killed and the daily weight change was recorded and proximal colon was collected for histologic examination. A histologic injury score was used to quantify the severity of mucosal injury. The severity of mucosal injury induced by luminal SCFAs administration decreased as the rats matured; by postnatal day 23, the injury caused by SCFAs was minimal. Thus, the severity of the colonic mucosal injury induced by luminal SCFAs is maturation dependent; the immature state of the mucosal defense in early postnatal age in newborn rat may explain its greater vulnerability to luminal SCFAs.