Altered hepatic and intestinal homeostasis in a neonatal murine model of short-term total parenteral nutrition and antibiotics.

Parenteral nutrition (PN) prevents starvation and supports metabolic requirements intravenously when patients are unable to be fed enterally. Clinically, infants are frequently provided PN in intensive care settings along with exposure to antibiotics (ABX) to minimize infection during care. Unfortunately, neonates experience extremely high rates of hepatic complications. Adult rodent and piglet models of PN are well-established but neonatal models capable of leveraging the considerable transgenic potential of the mouse remain underdeveloped. Utilizing our newly established neonatal murine PN mouse model, we administered ABX or controlled drinking water to timed pregnant dams to disrupt the maternal microbiome. We randomized mouse pups to PN or sham surgery controls +/- ABX exposure. ABX or short-term PN decreased liver and brain organ weights, intestinal length, and mucosal architecture (vs. controls). PN significantly elevated evidence of hepatic proinflammatory markers, neutrophils and macrophage counts, bacterial colony-forming units, and evidence of cholestasis risk, which was blocked by ABX. However, ABX uniquely elevated metabolic regulatory genes resulting in accumulation of hepatocyte lipids, triglycerides, and elevated tauro-chenoxycholic acid (TCDCA) in serum. Within the gut, PN elevated the relative abundance of Akkermansia, Enterococcus, and Suterella with decreased Anaerostipes and Lactobacillus compared with controls, whereas ABX enriched Proteobacteria. We conclude that short-term PN elevates hepatic inflammatory stress and risk of cholestasis in early life. Although concurrent ABX exposure protects against hepatic immune activation during PN, the dual exposure modulates metabolism and may contribute toward early steatosis phenotype, sometimes observed in infants unable to wean from PN.NEW & NOTEWORTHY This study successfully established a translationally relevant, murine neonatal parenteral nutrition (PN) model. Short-term PN is sufficient to induce hepatitis-associated cholestasis in a neonatal murine model that can be used to understand disease in early life. The administration of antibiotics during PN protects animals from bacterial translocation and proinflammatory responses but induces unique metabolic shifts that may predispose the liver toward early steatosis.

Efficacy of Sildenafil in Infants with Bronchopulmonary Dysplasia-Associated Pulmonary Hypertension.

Background: Pulmonary hypertension (PH) is a common comorbidity in infants with bronchopulmonary dysplasia (BPD). Sildenafil is a widely recognized therapy for PH, but its efficacy in infants with BPD is questionable. We propose to assess the efficacy of sildenafil in BPD-associated PH as evaluated based on transthoracic echocardiography (TTE) changes and clinical measures. Methods: Data were retrospectively and prospectively collected. Inclusion criteria were gestational age (GA) < 32 weeks, birth weight (BW) < 1500 g with severe BPD, diagnosis of PH via TTE on sildenafil treatment. PH was evaluated via TTE, which was performed monthly after 36 weeks post-menstrual age (PMA) as a standard of care, and re-reviewed by a single pediatric cardiologist, who was blind to the initial reading. Results: In total, 19 patients were enrolled in the study, having a median GA of 24 3/7 weeks (IQR 23 5/7-25 5/7) and a median BW of 598 g (IQR 572-735). Sildenafil treatment was started at a median PMA of 40.4 weeks. The median respiratory severity score (RSS) at 28 d was 6.5, RSS and FiO2 showed improvement about 12 weeks after starting sildenafil treatment. Conclusions: Improvement in PH was noted via TTE, and patients had improvement in their RSS and FiO2 after prolonged therapy. However, TTE improvements did not correlate with clinical improvements.

The fungal intestinal microbiota predict the development of bronchopulmonary dysplasia in very low birthweight newborns.

RATIONALE: Bronchopulmonary dysplasia (BPD) is the most common morbidity affecting very preterm infants. Gut fungal and bacterial microbial communities contribute to multiple lung diseases and may influence BPD pathogenesis. METHODS: We performed a prospective, observational cohort study comparing the multikingdom fecal microbiota of 144 preterm infants with or without moderate to severe BPD by sequencing the bacterial 16S and fungal ITS2 ribosomal RNA gene. To address the potential causative relationship between gut dysbiosis and BPD, we used fecal microbiota transplant in an antibiotic-pseudohumanized mouse model. Comparisons were made using RNA sequencing, confocal microscopy, lung morphometry, and oscillometry. RESULTS: We analyzed 102 fecal microbiome samples collected during the second week of life. Infants who later developed BPD showed an obvious fungal dysbiosis as compared to infants without BPD (NoBPD, p = 0.0398, permutational multivariate ANOVA). Instead of fungal communities dominated by Candida and Saccharomyces, the microbiota of infants who developed BPD were characterized by a greater diversity of rarer fungi in less interconnected community architectures. On successful colonization, the gut microbiota from infants with BPD augmented lung injury in the offspring of recipient animals. We identified alterations in the murine intestinal microbiome and transcriptome associated with augmented lung injury. CONCLUSIONS: The gut fungal microbiome of infants who will develop BPD is dysbiotic and may contribute to disease pathogenesis.

Use of Vasopressors in Extremely Preterm Infants in First Week of Life.

OBJECTIVE: A significant variability exists for diagnosis and treatment of hypotension in extremely preterm infants. Benefits of the use of vasopressors remain unclear. We wanted to identify the risk factors associated with use of vasopressors in the first week of life and their impact on outcomes of extremely preterm infants. STUDY DESIGN: Retrospective review of all newborns ≤28 weeks of gestational age (GA) admitted in neonatal intensive care unit from October 1, 2012, to October 31, 2015, done. Data regarding antenatal and neonatal characteristics and outcomes were recorded. Study infants were divided into two cohorts and compared based on vasopressor use. Chi-square, t-test, and multiple logistic regression were performed as appropriate and significance set at p <0.05. RESULTS: Of 213 extremely preterm infants, 90 (42.3%) received vasopressors in first week of life. The mean arterial pressure (MAP) at admission in these infants was significantly lower than that of infants who did not require vasopressors (27 ± 8 vs. 30 ± 6 mm Hg, p < 0.05). Vasopressors were initiated within 24 hours in 91% of babies. After controlling for other variables, use of vasopressors was significantly higher in infants with lower birth weight (odds ratio [OR]: 3.2, 95% confidence interval [CI]: 1.6-8.3), 5-minute Apgar's score ≤5 (OR: 1.8, 95% CI: 1.2-3.12), and admission hypothermia (OR: 2.7, 95% CI: 1.3-4.9). The use of vasopressors was significantly associated with severe intraventricular hemorrhage (IVH), even after controlling for other significant variables (OR: 5.9, 95% CI: 1.6-9.3). CONCLUSION: Lower birth weight, low 5-minute Apgar's score, and admission hypothermia are characteristics associated with early use of vasopressors in extremely preterm infants. Infants treated with vasopressors are at a higher risk of developing severe IVH. KEY POINTS: · Low systemic blood pressure is a very common problem in the extremely preterm population.. · In clinical practice, mean arterial blood pressure (BP) less than the infants GA in week is typically considered to be "low BP.". · About 50% of infants born at <29 weeks of GA received very preterm in the first week of life.. · Use of vasopressors is associated with a higher incidence of intraventricular hemorrhage in extremely preterm population..

Improving Red Reflex Screening in a Level III NICU Through a Quality Improvement-based Approach.

BACKGROUND: Red reflex is a routine part of newborn examination in most high-income countries. It is an inexpensive, noninvasive method of detecting serious ocular abnormalities like cataracts, retinoblastoma, vitreous masses, etc. The American Academy of Pediatrics recommends red reflex examination before discharge from newborn nursery. However, the current rate of red reflex examination in the NICUs in the United States is unknown. We noted a low rate of documentation (19%) in our level III NICU, prompting us to initiate this quality improvement project to improve this rate. METHODS: We created a key-driver diagram and summarized possible interventions to achieve our aim to increase the documentation rate to >80%. We implemented various interventions over 4 plan-do-study-act cycles. Over 19 months, we educated the nurses and the providers regarding the importance of red reflex assessment, placed visual reminders to check red reflex, implemented discharge checklist for the residents, and improved the accessibility to ophthalmoscope. RESULTS: Infants discharged from our NICU during a 25-month period included 1168 infants who an ophthalmologist did not formally examine. The rate of red reflex documentation improved significantly from a baseline of 19% (6 months before the first plan-do-study-act cycle) to 89.5% (during the 19-month intervention period). One abnormal red reflex was detected during this study. CONCLUSIONS: Implementation of this project has led to a culture change at our institution, which will help prevent us from missing the diagnosis of serious visual abnormalities in the future.

Effect of Whole-Genome Sequencing on the Clinical Management of Acutely Ill Infants With Suspected Genetic Disease: A Randomized Clinical Trial.

Importance: Whole-genome sequencing (WGS) shows promise as a first-line genetic test for acutely ill infants, but widespread adoption and implementation requires evidence of an effect on clinical management. Objective: To determine the effect of WGS on clinical management in a racially and ethnically diverse and geographically distributed population of acutely ill infants in the US. Design, Setting, and Participants: This randomized, time-delayed clinical trial enrolled participants from September 11, 2017, to April 30, 2019, with an observation period extending to July 2, 2019. The study was conducted at 5 US academic medical centers and affiliated children's hospitals. Participants included infants aged between 0 and 120 days who were admitted to an intensive care unit with a suspected genetic disease. Data were analyzed from January 14 to August 20, 2020. Interventions: Patients were randomized to receive clinical WGS results 15 days (early) or 60 days (delayed) after enrollment, with the observation period extending to 90 days. Usual care was continued throughout the study. Main Outcomes and Measures: The main outcome was the difference in the proportion of infants in the early and delayed groups who received a change of management (COM) 60 days after enrollment. Additional outcome measures included WGS diagnostic efficacy, within-group COM at 90 days, length of hospital stay, and mortality. Results: A total of 354 infants were randomized to the early (n = 176) or delayed (n = 178) arms. The mean participant age was 15 days (IQR, 7-32 days); 201 participants (56.8%) were boys; 19 (5.4%) were Asian; 47 (13.3%) were Black; 250 (70.6%) were White; and 38 (10.7%) were of other race. At 60 days, twice as many infants in the early group vs the delayed group received a COM (34 of 161 [21.1%; 95% CI, 15.1%-28.2%] vs 17 of 165 [10.3%; 95% CI, 6.1%-16.0%]; P = .009; odds ratio, 2.3; 95% CI, 1.22-4.32) and a molecular diagnosis (55 of 176 [31.0%; 95% CI, 24.5%-38.7%] vs 27 of 178 [15.0%; 95% CI, 10.2%-21.3%]; P < .001). At 90 days, the delayed group showed a doubling of COM (to 45 of 161 [28.0%; 95% CI, 21.2%-35.6%]) and diagnostic efficacy (to 56 of 178 [31.0%; 95% CI, 24.7%-38.8%]). The most frequent COMs across the observation window were subspecialty referrals (39 of 354; 11%), surgery or other invasive procedures (17 of 354; 4%), condition-specific medications (9 of 354; 2%), or other supportive alterations in medication (12 of 354; 3%). No differences in length of stay or survival were observed. Conclusions and Relevance: In this randomized clinical trial, for acutely ill infants in an intensive care unit, introduction of WGS was associated with a significant increase in focused clinical management compared with usual care. Access to first-line WGS may reduce health care disparities by enabling diagnostic equity. These data support WGS adoption and implementation in this population. Trail Registration: ClinicalTrials.gov Identifier: NCT03290469.

Management and short-term outcomes of neonates born to mothers with active perinatal SARS-CoV-2 infection.

OBJECTIVE: We report here on the management and outcomes of neonates born to mothers with active perinatal SARS-CoV-2 infection. STUDY DESIGN: In this prospective study, eligible neonates were enrolled in a database to track in-hospital outcomes and followed up outpatient periodically till 2 months of age to assess for late onset symptoms of infection. RESULTS: From April 2020 to February 2021, 67 mothers with perinatal SARS-CoV-2 infection and 70 at-risk neonates were included. Two neonates (3%) tested positive for SARS-CoV-2 within 48 h of life but remained asymptomatic during hospitalization and at all follow-up periods. Three infants were reported to have a febrile illness in 2 months follow up period, none of which was attributable to SARS-CoV-2. CONCLUSION: Our data supports the emerging evidence which describes a probable low risk of vertical transmission of SARS-CoV-2. We also demonstrate a low risk of post-natal transmission or late-onset symptomatic infection with SARS-CoV-2.

Kagami-Ogata Syndrome: Case Series and Review of Literature.

Kagami-Ogata syndrome (KOS) (OMIM #608149) is a genetic imprinting disorder affecting chromosome 14 that results in a characteristic phenotype consisting of typical facial features, skeletal abnormalities including rib abnormalities described as "coat hanger ribs," respiratory distress, abdominal wall defects, polyhydramnios, and developmental delay. First identified by Wang et al in 1991, over 80 cases of KOS have been reported in the literature. KOS, however, continues to remain a rare and potentially underdiagnosed disorder. In this report, we describe two unrelated male infants with differing initial presentations who were both found to have the characteristic "coat hanger" rib appearance on chest X-ray, raising suspicion for KOS. Molecular testing confirmed KOS in each case. In addition to these new cases, we reviewed the existing cases reported in literature. Presence of polyhydramnios, small thorax, curved ribs, and abdominal wall defects must alert the perinatologist toward the possibility of KOS to facilitate appropriate molecular testing. The overall prognosis of KOS remains poor. Early diagnosis allows for counseling by a multidisciplinary team and enables parents to make informed decisions regarding both pregnancy management and postnatal care.

The danger of diazoxide in the neonatal intensive care unit.

BACKGROUND: The most common cause of persistent hypoglycemia in infancy is hyperinsulinemic hypoglycemia. When conservative measures fail, providers often use medications to treat persistent hypoglycemia. Diazoxide is first-line therapy for neonatal hypoglycemia and works by inhibiting insulin secretion. Diazoxide is associated with fluid retention, and less commonly with respiratory decompensation and pulmonary hypertension. Case reports documenting these severe adverse events exist in the literature, although the overall incidence, risk factors, and timing for these effects in a newborn are not clearly defined. METHODS: We performed a retrospective chart review of all infants admitted to the neonatal intensive care unit (NICU) at Regional One Health from 1 January 2013 until 15 August 2019, who received diazoxide as a treatment for persistent hypoglycemia secondary to hyperinsulinism. Patients were stratified as either having no adverse event or having an adverse outcome to the medication. A severe adverse outcome was defined as any known major side effect of the medication, which a patient developed within 2 weeks of medication initiation that led to medication discontinuation. RESULTS: From our pharmacy database, we identified a total of 15 babies who received diazoxide for persistent hypoglycemia. Of these patients, eight (53%) were classified as having a complication requiring discontinuation of the medication. Six out of eight patients required intubation with mechanical ventilation and five out of eight patients developed pulmonary hypertension. All patients returned to their baseline respiratory support after drug discontinuation. CONCLUSIONS: A total of 53% of our study population had an adverse outcome to diazoxide. Previous studies suggest 5% of patients may have respiratory decompensation and require ventilatory support while on diazoxide; however, 40% of our patients deteriorated and then required mechanical ventilation. Based on our data, respiratory deterioration may be more likely to occur when diazoxide is used in preterm infants, those with lower birth weight and intrauterine growth restriction. PLAIN LANGUAGE SUMMARY: The dangers in diazoxide Newborns could experience a transient period of low blood glucose levels soon after birth. However, some may progress to persistent low blood glucose levels that cannot be controlled with adequate glucose infusion and may require other ways of treatment. Diazoxide is the first-line drug approved by the US Food and Drug Administration (FDA) for this condition. However, certain cases have reported the development of respiratory deterioration, including increased blood pressure in lung circulation after its use. This prompted a black box warning in 2015 by the FDA. The incidence of neonatal low blood glucose levels seems to have increased and so has the use of this drug. Our study identifies 15 newborns who received diazoxide at Regional One Health neonatal intensive care unit in the past 6 years and reports a significantly higher rate of adverse events in our population leading to drug discontinuation in almost 53% of our cases.

Outcomes of neonates with tracheostomy secondary to bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a disease that can affect preterm neonates. Infants with severe BPD may develop pulmonary hypertension (PHN) and may require chronic mechanical ventilation with tracheostomy. The outcomes of these infants have not been studied well. We proposed to review survival and outcomes of infants requiring tracheostomy secondary to severe BPD in our NICU at 24 months. METHODS: We reviewed infants' charts who were diagnosed with BPD that underwent tracheostomy from January 2011 to May 2016 at our children's hospital NICU. Data were recorded from hospital stay as well as from follow up clinics. Institutional review board approval was obtained prior to beginning of study. RESULTS: Forty-one babies (37 during initial hospitalization and 4 subsequently) requiring tracheostomy were identified from our database. Median gestational age at birth was 26 weeks (25-27 IQR), mean birthweight of 731 g (±245 SD) and 32% were small for gestational age (SGA). Median age of tracheostomy placement was 168 days (108-197 IQR), and median PMA 48 wks (40-56 IQR). 26% of infants requiring tracheostomy also had subglottic stenosis along with BPD. 34 infants (83%) survived to discharge from NICU. 66% (27/41) of our patients had a composite outcome of death, ventilator dependency and/or poor neurodevelopmental outcome at 2 years. We found that a higher respiratory severity score at the time of tracheostomy placement and later post-menstrual age at admission to level IV NICU was associated with a worse outcome. Small for gestational age infants were found to have worse outcomes as well. 41% (13/32) of infants had more than 3 hospital admissions after discharge. CONCLUSIONS: In our cohort about 80% of infants with severe BPD and tracheostomy survived to discharge with need for prolonged home ventilation in more than half of the survivors. Later postmenstrual age at admission to level 4 NICU was associated with a worse outcome. Our retrospective data may be inadequate to determine the causal relationship between postmenstrual age at admission and outcome. These patients continue to have high morbidity and recurrent hospitalizations.

Pulmonary Hypertension with Prolonged Patency of the Ductus Arteriosus in Preterm Infants.

There continues to be a reluctance to close the patent ductus arteriosus (PDA) in premature infants. The debate on whether the short-term outcomes translate to a difference in long-term benefits remains. This article intends to review the pulmonary vasculature changes that can occur with a chronic hemodynamically significant PDA in a preterm infant. It also explains the rationale and decision-making involved in a diagnostic cardiac catheterization and transcatheter PDA closure in these preterm infants.

Estimated fetal weight and severe neonatal outcomes in preterm prelabor rupture of membranes.

Objectives Our aim was to study the association of clinical variables obtainable before delivery for severe neonatal outcomes (SNO) and develop a clinical tool to calculate the prediction probability of SNO in preterm prelabor rupture of membranes (PPROM). Methods This was a prospective study from October 2015 to May 2018. We included singleton pregnancies with PPROM and an estimated fetal weight (EFW) two weeks before delivery. We excluded those with fetal anomalies or fetal death. We examined the association between SNO and variables obtainable before delivery such as gestational age (GA) at PPROM, EFW, gender, race, body mass index, chorioamnioitis. SNO was defined as having at least one of the following: respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, neonatal sepsis, or neonatal death. The most parsimonious logistic regression models was constructed using the best subset selection model approach, and receiver operator curves were utilized to evaluate the prognostic accuracy of these clinical variables for SNO. Results We included 106 pregnancies, 42 had SNO (39.6%). The EFW (area under the receiver operating characteristic curve [AUC]=0.88) and GA at PPROM (AUC=0.83) were significant predictors of SNO. The addition of any of the other variables did not improve the predictive probability of EFW for the prediction of SNO. Conclusions The EFW had the strongest association with SNO in in our study among variables obtainable before delivery. Other variables had no significant effect on the prediction probability of the EFW. Our findings should be validated in larger studies.

Comparison of institutional guidelines with established early onset sepsis risk calculator in reducing antibiotic use in an inner-city NICU in US.

OBJECTIVES: Early onset sepsis (EOS) incidence has decreased since national guidelines and intrapartum prophylaxis were introduced. However, there has been a rising concern in antibiotic overtreatment for suspicion of EOS. A web-based EOS calculator has recently been used to evaluate the risk in newborns ≥34 weeks. Our purpose was to compare local strategies with the EOS calculator in our setting with an EOS incidence of 2/1000 live births. METHODS: A retrospective review of all newborns born ≥34 weeks from 1 January 2016 to 31 December 2017 was completed after receiving IRB approval. We applied the calculator to those eligible using an EOS incidence of 0.6/1000 and 2/1000 live births and divided the patients into four cohorts. The rate of antibiotic use was compared between local evidence-based guidelines and the EOS calculator. RESULTS: Of the 1367 newborns included in the study, 679 received antibiotics. Over the 2 years, antibiotic utilization decreased by 38%. The calculator would have recommended antibiotics for 468 patients (31% decrease) for an EOS incidence of 0.6/1000, but with a 2/1000 incidence rate the calculator recommended antibiotics for 673 patients (1% decrease). CONCLUSIONS: The EOS calculator has been helpful in optimizing antibiotic use, but its use may result in suboptimal treatment without the knowledge of local EOS incidence. Our local antibiotic stewardship guidelines seemed to be comparable to the EOS calculator, especially by the last 6 months of the study period.

TGR5 signaling mitigates parenteral nutrition-associated liver disease.

Bile acid receptors regulate the metabolic and immune functions of circulating enterohepatic bile acids. This process is disrupted by administration of parenteral nutrition (PN), which may induce progressive hepatic injury for unclear reasons, especially in the newborn, leading to PN-associated liver disease. To explore the role of bile acid signaling on neonatal hepatic function, we initially observed that Takeda G protein receptor 5 (TGR5)-specific bile acids were negatively correlated with worsening clinical disease markers in the plasma of human newborns with prolonged PN exposure. To test our resulting hypothesis that TGR5 regulates critical liver functions to PN exposure, we used TGR5 receptor deficient mice (TGR5-/-). We observed PN significantly increased liver weight, cholestasis, and serum hepatic stress enzymes in TGR5-/- mice compared with controls. Mechanistically, PN reduced bile acid synthesis genes in TGR5-/-. Serum bile acid composition revealed that PN increased unconjugated primary bile acids and secondary bile acids in TGR5-/- mice, while increasing conjugated primary bile acid levels in TGR5-competent mice. Simultaneously, PN elevated hepatic IL-6 expression and infiltrating macrophages in TGR5-/- mice. However, the gut microbiota of TGR5-/- mice compared with WT mice following PN administration displayed highly elevated levels of Bacteroides and Parabacteroides, and possibly responsible for the elevated levels of secondary bile acids in TGR5-/- animals. Intestinal bile acid transporters expression was unchanged. Collectively, this suggests TGR5 signaling specifically regulates fundamental aspects of liver bile acid homeostasis during exposure to PN. Loss of TGR5 is associated with biochemical evidence of cholestasis in both humans and mice on PN.NEW & NOTEWORTHY Parenteral nutrition is associated with deleterious metabolic outcomes in patients with prolonged exposure. Here, we demonstrate that accelerated cholestasis and parental nutrition-associated liver disease (PNALD) may be associated with deficiency of Takeda G protein receptor 5 (TGR5) signaling. The microbiome is responsible for production of secondary bile acids that signal through TGR5. Therefore, collectively, these data support the hypothesis that a lack of established microbiome in early life or under prolonged parenteral nutrition may underpin disease development and PNALD.

Management of Patent Ductus Arteriosus in Premature Infants in 2020.

The patent ductus arteriosus (PDA) is the most commonly found cardiac condition in neonates. While there have been several studies and thousands of publications on the topic, the decision to treat the PDA is still strongly debated among cardiologists, surgeons, and neonatologists. This is in part due to the shortage of long-term benefits with the interventions studied. Practice variations still exist within sub-specialties and centers. This article briefly summarizes the history, embryology and histology of the PDA. It also succinctly discusses the hemodynamic significance of a PDA which builds the framework to review all the available literature on PDA closure in premature infants, though not a paradigm shift just yet; it introduces transcatheter PDA closure (TCPC) as a possible armament to the clinician for this age-old problem.

Fetal pulmonary artery acceleration/ejection time prognostic accuracy for respiratory complications in preterm prelabor rupture of membranes.

Objective: To determine the prognostic accuracy of the fetal pulmonary artery acceleration time/ejection time (PATET) for the prediction of neonatal respiratory complications (NRCs) in pregnancies with preterm premature rupture of membranes (PPROM).Methods: This is a prospective cohort of singleton pregnancies complicated by PPROM managed in our institution from October 2015 to April 2018. Inclusion criteria included mothers from 13 to 46 years of age and singleton pregnancies with PATET measurements <7 days prior to delivery. PATET was obtained by placing the Doppler caliper in the main pulmonary artery proximal to the bifurcation of this vessel. NRC was defined as: need for ventilatory support, respiratory distress syndrome (RDS), or lung hypoplasia. Logistic regression models and area under the receiver operating characteristic curves (ROC) were utilized to determine the prognostic accuracy of PATET and gestational age for NRC and RDS.Results: Of 95 patients included, 46 had NRC (RDS = 33). PATET was a significant predictor of NRC (AUC 0.74; 95%CI: 0.61-0.83; p < .001) and RDS (AUC 0.69; 95%CI: 0.57-0.80; p = .021) in PPROM. Gestational age at delivery and gestational age at PPROM were also significantly associated with NRC and RDS. Their predictive accuracy for NRC was 0.87 and 0.84, and for RDS 0.85 and 0.86, respectively.Conclusions: PATET is a statistically significant predictor for NRC in pregnancies with PPROM; however, its clinical use may be limited as gestational age is a better predictor of these outcomes.Rationale: NRCs are common in pregnancies complicated by preterm prelabor rupture of membranes (PPROM). We aim to determine the prognostic accuracy of the fetal PATET for the prediction of neonatal NRC in these pregnancies. Our results indicate that PATET is a statistically significant predictor for NRC in pregnancies with PPROM; however, its clinical use may be limited, as gestational age is a better predictor of these outcomes.

Perinatal maternal antibiotic exposure augments lung injury in offspring in experimental bronchopulmonary dysplasia.

During the newborn period, intestinal commensal bacteria influence pulmonary mucosal immunology via the gut-lung axis. Epidemiological studies have linked perinatal antibiotic exposure in human newborns to an increased risk for bronchopulmonary dysplasia, but whether this effect is mediated by the gut-lung axis is unknown. To explore antibiotic disruption of the newborn gut-lung axis, we studied how perinatal maternal antibiotic exposure influenced lung injury in a hyperoxia-based mouse model of bronchopulmonary dysplasia. We report that disruption of intestinal commensal colonization during the perinatal period promotes a more severe bronchopulmonary dysplasia phenotype characterized by increased mortality and pulmonary fibrosis. Mechanistically, metagenomic shifts were associated with decreased IL-22 expression in bronchoalveolar lavage and were independent of hyperoxia-induced inflammasome activation. Collectively, these results demonstrate a previously unrecognized influence of the gut-lung axis during the development of neonatal lung injury, which could be leveraged to ameliorate the most severe and persistent pulmonary complication of preterm birth.

Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age.

Fungal and bacterial commensal organisms play a complex role in the health of the human host. Expansion of commensal ecology after birth is a critical period in human immune development. However, the initial fungal colonization of the primordial gut remains undescribed. To investigate primordial fungal ecology, we performed amplicon sequencing and culture-based techniques of first-pass meconium, which forms in the intestine prior to birth, from a prospective observational cohort of term and preterm newborns. Here, we describe fungal ecologies in the primordial gut that develop complexity with advancing gestational age at birth. Our findings suggest homeostasis of fungal commensals may represent an important aspect of human biology present even before birth. Unlike bacterial communities that gradually develop complexity, the domination of the fungal communities of some preterm infants by Saccromycetes, specifically Candida, may suggest a pathologic association with preterm birth.-Willis, K. A., Purvis, J. H., Myers, E. D., Aziz, M. M., Karabayir, I., Gomes, C. K., Peters, B. M., Akbilgic, O., Talati, A. J., Pierre, J. F. Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age.

Improving neonatal resuscitation in Tennessee: a large-scale, quality improvement project.

OBJECTIVE: We report a statewide collaborative quality initiative to improve resuscitation and stabilization practices following introduction of the 6th edition of the Neonatal Resuscitation Program. METHODS: Participants drafted a consensus toolkit of interventions and corresponding measures. Hospital teams collected baseline data, and implemented changes using PDSA-cycles and statistical process control charts. RESULTS: Nine Tennessee NICUs submitted data on 3771 resuscitations. "Special cause" improvements were achieved and sustained for pre-resuscitation checklists (77-90%) and team briefings (80-92%). Time to intravenous access (50-42 min), glucose infusion initiation (73-60 min), and antibiotic dosing (113-98 min) were also significantly reduced. Teams were unable to meet new NRP oxygen saturation targets. Improvements in post-resuscitation debriefing were not sustained, while communication with parents declined significantly (68-60%). CONCLUSION: Large-scale collaboration facilitated statewide implementation of new guidelines, while highlighting under-appreciated systems challenges among competing resource demands.