Need for Gastrostomy Tube in Periviable Infants.

OBJECTIVE: We sought to identify clinical and demographic factors associated with gastrostomy tube (g-tube) placement in periviable infants. STUDY DESIGN: We conducted a single-center retrospective cohort study of live-born infants between 22 and 25 weeks' gestation. Infants not actively resuscitated and those with congenital anomalies were excluded from analysis. RESULTS: Of the 243 infants included, 158 survived until discharge. Of those that survived to discharge, 35 required g-tube prior to discharge. Maternal race/ethnicity (p = 0.006), intraventricular hemorrhage (p = 0.013), periventricular leukomalacia (p = 0.003), bronchopulmonary dysplasia (BPD; p ≤ 0.001), and singleton gestation (p = 0.009) were associated with need for gastrostomy. In a multivariable logistic regression, maternal Black race (Odds Ratio [OR] 2.88; 95% confidence interval [CI] 1.11-7.47; p = 0.029), singleton gestation (OR 3.99; 95% CI 1.28-12.4; p = 0.017) and BPD (zero g-tube placement in the no BPD arm; p ≤ 0.001) were associated with need for g-tube. CONCLUSION: A high percentage of periviable infants surviving until discharge require g-tube at our institution. In this single-center retrospective study, we noted that maternal Black race, singleton gestation, and BPD were associated with increased risk for g-tube placement in infants born between 22 and 25 weeks' gestation. The finding of increased risk with maternal Black race is consistent with previous reports of racial/ethnic disparities in preterm morbidities. Additional studies examining factors associated with successful achievement of oral feedings in preterm infants are necessary and will inform future efforts to advance equity in newborn health. KEY POINTS: · BPD, singleton birth, and Black race are associated with need for g-tube in periviable infants.. · Severe intraventricular hemorrhage is associated with increased mortality or g-tube placement in periviable infants.. · Further investigation into the relationship between maternal race and g-tube placement is warranted..

Lower Urinary Tract Obstruction in Newborns.

Lower urinary tract obstruction (LUTO) is a rare birth defect with a prevalence between 1 in 5,000 and 1 in 25,000 pregnancies. LUTO is one of the most common causes of congenital abnormalities of the renal tract. Several genetic conditions have been associated with LUTO. Most common causes of LUTO are posterior urethral valves and urethral atresia. Despite available prenatal and postnatal treatments, LUTO is a significant cause of morbidity and mortality in newborns causing significant end stage renal disease and pulmonary hypoplasia.

Gastroschisis Outcomes: Presence of Histologic Chorioamnionitis and the Impact on Time to Full Enteral Feeds and Length of Hospital Stay.

OBJECTIVE: Despite improvements in our ability for early diagnosis and providing supportive care for infants with gastroschisis, it continues to be associated with long length of stay and morbidity. Intestinal dysfunction secondary to chronic inflammatory insult to exposed bowel is well known; however, little research has been done on the impact of acute inflammation in the perinatal period on intestinal function. This study's aim was to investigate the impact of acute chorioamnionitis on the time to achieve full enteral feeds and length of hospital stay. STUDY DESIGN: Retrospective chart review of 60 mothers and their infants born with gastroschisis at a Level IV NICU from November 2011 to June 2020 was performed. Infants were divided into two groups based on the presence of histologic chorioamnionitis, and outcomes were compared. The primary outcome was delayed full enteral feeds (full enteral feeds after 28 days of life). The secondary outcomes were differences in their time to achieve full enteral feeds and time to hospital discharge, and prolonged length of hospital stay (discharge after 30 days of life). Univariate and multivariate logistic regression analyses were performed to assess the association between the dependent and the predictor variables. RESULT: Of the 60 infants enrolled, 23 (38%) had evidence of histologic chorioamnionitis. The median gestational age was 37 weeks. Fifty-four (90%) infants achieved full enteral feeds, with a median time of 24 days. Median length of hospital stay was 31 days. The presence of histologic chorioamnionitis was not associated with delayed full enteral feeds (odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.14-4.23; p = 0.80) or prolonged length of hospital stay (OR = 0.45; 95% CI = 0.1-0.23; p = 0.32) in the adjusted analysis. CONCLUSION: Acute placental inflammation during the perinatal period does not impact the infant's time to achieve full feeds or prolong their hospital stay. Larger studies are needed to confirm these findings. KEY POINTS: · Chronic inflammatory injury to exposed bowel in utero is well known in fetuses with gastroschisis.. · Acute inflammatory injury during perinatal period may impact enteral feeding outcomes.. · No impact of acute placental inflammation on time to full enteral feeds..

The Impact of Mode of Delivery on Maternal and Neonatal Outcomes during Periviable Birth (22-25 Weeks).

OBJECTIVE: The objective of our study was to compare the maternal and neonatal complications of periviable birth by the delivery route. STUDY DESIGN: A retrospective cohort study of periviable deliveries (220/7-256/7weeks) from 2013 to 2020 at a tertiary teaching institution was conducted. Deliveries were grouped by the mode of delivery. Excluded deliveries included pregnancy termination, anomaly, or undesired neonatal resuscitation. The primary composite maternal outcome included death, intensive care admission, sepsis, surgical site infection, unplanned operation, or readmission. Secondary outcomes included maternal blood loss, length of stay, neonatal survival, bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), and retinopathy of prematurity (ROP). Outcomes were compared using Student's t-test, Wilcoxon-Mann-Whitney and Chi-squared tests. Relative risk (RR) and 95% confidence intervals were calculated with log-binomial regression. p-Values <0.05 were considered significant. Demographic and intervention variables associated with the outcome and the exposure were included in an adjusted relative risk (aRR) model. Subgroup analyses of singleton pregnancies and 220/7 to 236/7 weeks deliveries were conducted. RESULTS: After exclusion, 230 deliveries were included in the cohort. Maternal characteristics were similar between cohorts. For the primary outcome, cesarean delivery was associated with a trend toward increased maternal morbidity (22.6 vs. 10.7%, RR = 2.11 [1.03-4.43], aRR = 1.95 [0.94-4.03], p-value 0.07). Administration of magnesium sulfate, antenatal corticosteroids, and tocolytics were similar between cohorts. Neonatal survival to discharge was not different between the groups (54/83, 65.1% vs. 118/191, 61.8%, aRR = 0.93 [0.77-1.13]). Among the 172 neonates discharged alive, there was no difference in BPD, IVH, NEC, PDA, ROP, or intact survival. CONCLUSION: Periviable birth has a high rate of maternal morbidity with a trend toward the highest risk among women undergoing cesarean delivery. These risks should be included in shared decision-making. KEY POINTS: · Periviable birth has high maternal morbidity (19%) and is highest after cesarean delivery (23%).. · Route of delivery does not impact neonatal survival or intact neonatal survival.. · Head entrapment is rare during vaginal breech delivery..

PIGA Mutations Can Mimic Neonatal Hemochromatosis.

Neonatal hemochromatosis (NH), one of the most common causes of liver failure in the neonate, often causes fetal loss or death during the neonatal period. Most cases are thought to be due to gestational alloimmune disease; however, other rare causes have been reported. NH is generally considered congenital and familial but not heritable. We present an infant diagnosed with NH whose clinical course differed significantly from that of most NH cases: at 11 months of age he had normal levels of liver enzymes, ferritin, and bilirubin, and normal neurodevelopment. This term male infant was born with a history of intrauterine growth restriction, oligohydramnios, and pericardial effusion. On day of life 1, he had hyperbilirubinemia and transaminitis; on day of life 3, ferritin was elevated; and on day of life 9, an MRI revealed iron deposits in the liver and renal cortex. Phenotypic features prompted a genetics consult. Whole-exome sequencing revealed a variant in the phosphatidylinositol glycan biosynthesis class A protein (PIGA) gene. Germ-line PIGA mutations are generally thought to be lethal in utero; however, there are reports of infants with PIGA mutations associated with dysmorphic features, neurologic manifestations, biochemical perturbations, and systemic iron overload; development can be normal up to 6 months of age. Because of the differences between infants with NH versus PIGA germ-line mutations in inheritance, prognosis, and natural history of disease, we propose that PIGA gene testing should be considered when evaluating newborns who present with NH.

Aerosolized Calfactant for Newborns With Respiratory Distress: A Randomized Trial.

BACKGROUND: Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. METHODS: A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers' discretion. RESULTS: Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P < .0001). Respiratory outcomes up to 28 days of age were no different. CONCLUSIONS: In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.

Trinitrobenzene sulfonic acid-induced intestinal injury in neonatal mice activates transcriptional networks similar to those seen in human necrotizing enterocolitis.

BACKGROUND: We have shown previously that enteral administration of 2, 4, 6-trinitrobenzene sulfonic acid in 10-d-old C57BL/6 pups produces an acute necrotizing enterocolitis with histopathological and inflammatory changes similar to human necrotizing enterocolitis (NEC). To determine whether murine neonatal 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-mediated intestinal injury could be used as a NEC model, we compared gene expression profiles of TNBS-mediated intestinal injury and NEC. METHODS: Whole-genome microarray analysis was performed on proximal colon from control and TNBS-treated pups (n = 8/group). For comparison, we downloaded human microarray data of NEC (n = 5) and surgical control (n = 4) from a public database. Data were analyzed using the software programs Partek Genomics Suite and Ingenuity Pathway Analysis. RESULTS: We detected extensive changes in gene expression in murine TNBS-mediated intestinal injury and human NEC. Using fold-change cut-offs of ±1.5, we identified 4,440 differentially-expressed genes (DEGs) in murine TNBS-mediated injury and 1,377 in NEC. Murine TNBS-mediated injury and NEC produced similar changes in expression of orthologous genes (r = 0.611, P < 0.001), and also activated nearly-identical biological processes and pathways. Lipopolysaccharide was top predicted upstream regulator in both the murine and human datasets. CONCLUSION: Murine neonatal TNBS-mediated enterocolitis and human NEC activate nearly-identical biological processes, signaling pathways, and transcriptional networks.

The gut of geographically disparate Ciona intestinalis harbors a core microbiota.

It is now widely understood that all animals engage in complex interactions with bacteria (or microbes) throughout their various life stages. This ancient exchange can involve cooperation and has resulted in a wide range of evolved host-microbial interdependencies, including those observed in the gut. Ciona intestinalis, a filter-feeding basal chordate and classic developmental model that can be experimentally manipulated, is being employed to help define these relationships. Ciona larvae are first exposed internally to microbes upon the initiation of feeding in metamorphosed individuals; however, whether or not these microbes subsequently colonize the gut and whether or not Ciona forms relationships with specific bacteria in the gut remains unknown. In this report, we show that the Ciona gut not only is colonized by a complex community of bacteria, but also that samples from three geographically isolated populations reveal striking similarity in abundant operational taxonomic units (OTUs) consistent with the selection of a core community by the gut ecosystem.

A Basal chordate model for studies of gut microbial immune interactions.

Complex symbiotic interactions at the surface of host epithelia govern most encounters between host and microbe. The epithelium of the gut is a physiologically ancient structure that is comprised of a single layer of cells and is thought to possess fully developed immunological capabilities. Ciona intestinalis (sea squirt), which is a descendant of the last common ancestor of all vertebrates, is a potentially valuable model for studying barrier defenses and gut microbial immune interactions. A variety of innate immunological phenomena have been well characterized in Ciona, of which many are active in the gut tissues. Interactions with gut microbiota likely involve surface epithelium, secreted immune molecules including variable region-containing chitin-binding proteins, and hemocytes from a densely populated laminar tissue space. The microbial composition of representative gut luminal contents has been characterized by molecular screening and a potentially relevant, reproducible, dysbiosis can be induced via starvation. The dialog between host and microbe in the gut can be investigated in Ciona against the background of a competent innate immune system and in the absence of the integral elements and processes that are characteristic of vertebrate adaptive immunity.