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.

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..

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.

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.

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.

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.

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.

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.

Group B Streptococci Induce Proinflammatory Responses via a Protein Kinase D1-Dependent Pathway.

Group B streptococci (GBS) are one of the leading causes of life-threatening illness in neonates. Proinflammatory responses to GBS mediated through host innate immune receptors play a critical role in the disease manifestation. However, the mechanisms involved in proinflammatory responses against GBS, as well as the contribution of signaling modulators involved in host immune defense, have not been fully elucidated. In the present study, we investigated the role of protein kinase D (PKD)1 in the proinflammatory responses to GBS. We found that both live and antibiotic-killed GBS induce activation of PKD1 through a pathway that is dependent on the TLR signaling adaptor MyD88 and its downstream kinase IL-1R-associated kinase 1, but independent of TNFR-associated factor 6. Our studies using pharmacological PKD inhibitors and PKD1-knockdown macrophages revealed that PKD1 is indispensable for GBS-mediated activation of MAPKs and NF-κB and subsequent expression of proinflammatory mediators. Furthermore, systemic administration of a PKD inhibitor protects d-galactosamine-sensitized mice from shock-mediated death caused by antibiotic-killed GBS. These findings imply that PKD1 plays a critical regulatory role in GBS-induced proinflammatory reactions and sepsis, and inhibition of PKD1 activation together with antibiotic treatment in GBS-infected neonates could be an effective way to control GBS diseases.

Glycerin Suppositories Use in Very Low Birth Weight Infants.

Objective To study the characteristics of very low birth weight (VLBW) infants receiving glycerin suppositories (GS) and evaluate the association of GS use with outcomes. Study Design This is a retrospective study of VLBW infants admitted to a level III neonatal intensive care unit. Infants with birth weight between 500 and 1,499 g were evaluated. We evaluated the frequency of GS use and compared the characteristics and outcomes of the GS group with the no-GS group. Multivariate analyses controlling for gestational age and small for gestational age status were performed to study the effect of GS on outcomes. Results A total of 1,073 infants were included in the study. Out of those, 527 (49.1%) infants received GS. Incidence of necrotizing enterocolitis was not significantly different between the two groups, while days to reach full enteral feeds and length of hospital stay were significantly longer in the GS group. Conclusion Frequent use of GS warrants further prospective studies to evaluate its safety and efficacy in view of our study showing association with longer time to reach full enteral feeds. We speculate that GS use could be a marker for gastrointestinal dysmotility and hence the association with unfavorable clinical outcomes.

Neonatal Hospital Course and Outcomes of Live-born Infants with Trisomy 18 at Two Tertiary Care Centers in the United States.

Objectives Trisomy 18 is presumed to be a lethal chromosomal abnormality; medical management of infants with this aneuploidy is controversial. Our objective was to describe our approach and experience with trisomy 18 infants. Study Design We reviewed the initial hospital course, management, and factors predicting discharge from the hospital from two large tertiary care neonatal intensive care units in the southern United States over 26 years. Results Of the 29 infants with trisomy 18, 21 (72%) died in the hospital and 8 (28%) were discharged home. 19 (66%) infants received mechanical ventilation and 10 (34%) received inotropic medications. Eight infants had critical congenital heart defects; only one survived to discharge. Three infants underwent major surgeries; one cardiac surgery, one tracheoesophageal fistula repair, and one myelomeningocele repair. Median length of hospital stay was 14 days (range, 0-78) for all the infants and 31 days (range, 18-66) for those that were discharged home. Factors associated with discharge from the hospital were female sex, higher gestational age, and absence of critical congenital heart defects. Median survival time was 13 days and was significantly longer for females compared with males. Our 1-month and 1-year survival rates were 31% and 3.9% respectively. Conclusion A significant proportion of infants with trisomy 18 were discharged home. These data are helpful in counseling parents of infants with trisomy 18.

Early versus Delayed Human Milk Fortification in Very Low Birth Weight Infants-A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of initiating human milk fortification at 2 different feeding volumes on feeding intolerance and the time to reach full feeding volume. STUDY DESIGN: Very low birth weight infants (n = 100) were prospectively randomized to early fortification (EF) (beginning at a feeding volume of 20 mL/kg/d) or delayed fortification (at a feeding volume of 100 mL/kg/d). We employed a standardized feeding protocol and parenteral nutrition guidelines for the nutritional management of all study infants. RESULTS: The median days to reach full feeding volumes were equivalent in the 2 groups (20 vs 20, P = .45). No significant difference was observed in the total number of episodes of feeding intolerance (58 vs 57). Two cases of necrotizing enterocolitis (Bell stage ≥2) and deaths occurred in each group. Median daily protein intake (g/kg/d) was higher in EF group in week 1 (3.3 [3.2, 3.5] vs 3.1 [2.9, 3.3], P < .001), week 2 (3.6 [3.5, 3.8] vs 3.2 [2.9, 3.4], P < .001), and week 3 (3.7 [3.4, 3.9] vs 3.5 [2.8, 3.8], P = .006). Cumulative protein intake (g/kg) in the first 4 weeks of life was higher in EF group (98.6 [93.8, 104] vs 89.6 [84.2, 96.4], P < .001). CONCLUSIONS: Very early human milk fortification may improve early protein intake in very low birth weight infants without increasing frequencies of adverse events. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01988792.

Trends in Medication Use in Very Low-Birth-Weight Infants in a Level 3 NICU over 2 Decades.

OBJECTIVE: This study aims to study the association between trends in medication utilization and survival in very low-birth-weight (VLBW) infants over a 22-year period. STUDY DESIGN: Medications received by VLBW infants were extracted retrospectively for the four periods 1990 to 1994, 1995 to 2000, 2001 to 2005, and 2006 to 2011 from our perinatal database and stratified by two birth weight groups: ≤ 1,000 g and 1,001 to 1,500 g. RESULT: A total of 5,529 VLBW infants were reviewed. The majority of them were African American (78%), with an increasing proportion over time. The median number of medications per patient in all VLBW infants remained similar over time, 9 (5, 15). A cardiovascular group of medications was most commonly used, with a significant increase in the use of dobutamine and indomethacin. A significant trend toward an increasing number of infants without any antibiotic exposure was also noted. Survival steadily and significantly increased from 83 to 87%. CONCLUSION: The trends of overall medication use remained the same in our neonatal intensive care unit (NICU) over the past 22 years. There was no association between medication utilization and survival. VLBW infants continue to receive a high number of medications in the NICU, including a variety of antibiotics.

Preterm Infants Can Mount Appropriate C-Reactive Protein Responses to Early Onset Sepsis.

OBJECTIVE: This study aims to evaluate whether infants born at ≤ 32 weeks' gestational age (GA) can mount C-reactive protein (CRP) responses during early onset bacterial sepsis that are comparable to infants born at > 32 weeks' GA. METHODS: Retrospectively (2003-2012) infants with a positive bacterial culture during the first 72 hours of life were identified and grouped into two categories based on their GA: ≤ 32 weeks (group A) and > 32 weeks (group B). RESULTS: Group A included 25 and group B included 122 infants. Both groups responded similarly to sepsis with an increase in CRP (p = 0.59). Each group had a significant change in intragroup CRP levels over time (p < 0.0001). However, in both groups, the degree of this change was at the same rate over time (p = 0.74). CONCLUSION: CRP responses to bacterial sepsis during the first 72 hours of life in infants born at ≤ 32 weeks' GA are comparable to infants born at > 32 weeks' GA.

Trends of Staphylococcus aureus bloodstream infections in a neonatal intensive care unit from 2000-2009.

BACKGROUND: Invasive methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) infections are major causes of numerous neonatal intensive care unit (NICU) outbreaks. There have been increasing reports of MRSA outbreaks in various neonatal intensive care units (NICUs) over the last decade. Our objective was to review the experience of Staphylococcus aureus sepsis in our NICU in the last decade and describe the trends in the incidence of Staphylococcus aureus blood stream infections from 2000 to 2009. METHODS: A retrospective perinatal database review of all neonates admitted to our NICU with blood cultures positive for Staphylococcus aureus from (Jan 1st 2000 to December 31st 2009) was conducted. Infants were identified from the database and data were collected regarding their clinical characteristics and co-morbidities, including shock with sepsis and mortality. Period A represents patients admitted in 2000-2003. Period B represents patients seen in 2004-2009. RESULTS: During the study period, 156/11111 infants were identified with Staphylococcus aureus blood stream infection: 41/4486 (0.91%) infants in Period A and 115/6625 (1.73%) in Period B (p < 0.0004). Mean gestation at birth was 26 weeks for infants in both periods. There were more MRSA infections in Period B (24% vs. 55% p < 0.05) and they were associated with more severe outcomes. In comparing the cases of MRSA infections observed in the two periods, infants in period B notably had significantly more pneumonia cases (2.4% vs. 27%, p = 0.0005) and a significantly higher mortality rate (0% vs. 15.7%, p = 0.0038). The incidences of skin and soft tissue infections and of necrotizing enterocolitis were not significantly changed in the two periods. CONCLUSION: There was an increase in the incidence of Staphylococcus aureus infection among neonates after 2004. Although MSSA continues to be a problem in the NICU, MRSA infections were more prevalent in the past 6 years in our NICU. Increased severity of staphylococcal infections and associated rising mortality are possibly related to the increasing MRSA infections with a more virulent community-associated strain.

A Comparison of Sequelae After a Practice Change From Vancomycin to Ampicillin Containing Antibiotic Regimens for Necrotizing Enterocolitis.

The aim of this study was to compare sequelae and acute kidney injury (AKI) occurrence among patients with necrotizing enterocolitis (NEC) after changing institutional guidelines replacing vancomycin with ampicillin for gram-positive coverage. This was a retrospective, single-center cohort analysis of patients from 2016-2020 (n = 73) with NEC at a surgical neonatal intensive care unit with a high community prevalence of methicillin-resistant Staphylococcus aureus (MRSA). Multivariate logistic regression was utilized to assess associations. Twenty-five (34%) patients had at least 1 sequela related to NEC. Ampicillin containing regimens were not associated with any sequelae type or AKI. Postmenstrual age < 29 weeks at diagnosis ([OR] 5.8 [1.2-28.8], P = .03; and receipt of vasopressors [OR] 3.3 [1.1-10.2], P = .04) were independently associated with sequalae. Stage III NEC was independently associated with AKI, OR 10.6 (2-55.6), P = .005. In conclusion, ampicillin-containing regimens are effective for NEC management at our institution despite a high prevalence of MRSA.

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.

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.