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..

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.

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.

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.

Reducing Severe Intraventricular Hemorrhage in Preterm Infants With Improved Care Bundle Adherence.

BACKGROUND AND OBJECTIVES: Intraventricular hemorrhage prevention bundles (IVHPBs) can decrease the incidence of intraventricular hemorrhage (IVH) in premature infants. Our center had a high rate of severe (grade III/IV) IVH (9.8%), and poor adherence (24%) to an IVHPB in neonates born ≤1250 g or ≤30 gestational weeks. Improvement initiatives were planned to decrease the incidence of severe IVH by 30% over 2 years. METHODS: A multidisciplinary team undertook interventions including in-service training, prompt initiation of IVHPB, revision of guidelines, and process standardization. Baseline data were collected from May 2016 to June 2018, with interventions occurring from July 2018 to May 2020. Adherence to the IVHPB was the primary process measure, and incidence of severe IVH the primary outcome measure. Control charts were used to analyze the effect of interventions on outcome. Balancing measures included use of breast milk at discharge, use of mechanical ventilation after initial resuscitation, and bronchopulmonary dysplasia. RESULTS: A total of 240 infants were assessed preintervention, and 185 during interventions. Adherence to the IVHPB improved from 24% to 88%. During this period, the incidence of severe IVH decreased from 9.8% to 2.4%, a 76% reduction from baseline. A higher adherence score was associated with reduced odds of IVH (odds ratio 0.30; 95% confidence interval 0.10-0.90, P = .03). CONCLUSIONS: Interventions focused on enhancing adherence to an IVHPB were associated with a reduced rate of severe IVH in high-risk neonates, highlighting the importance of assessing adherence to clinical guidelines.

Feeding volume advancement in preterm neonates: A level 4 neonatal intensive care unit quality improvement initiative.

INTRODUCTION: Because of provider variability in feeding guideline application, a quality improvement (QI) initiative was begun to better standardize feeding initiation and advancement for preterm infants. Our specific, measurable, achievable, relevant, and timely aims included decreasing the time to reach full feeds by 35% and reducing the duration of central lines by 30% over 12 months in infants born between 25 and 30 weeks' gestation or with birth weight between 600 and 1250 g. METHODS: Registered dietitians tracked central line days, parenteral nutrition (PN), enteral nutrition, fortification, guideline adherence, anthropometrics, necrotizing enterocolitis (NEC) cases, and central line-associated bloodstream infections (CLABSIs). QI progress charts were reviewed monthly. RESULTS: Mean central line days decreased from 7.3 to 5.8. Days of PN decreased from 6.7 to 5.1. The day of life that enteral feeds were started decreased from 1.1 to 0.5. The number of days between starting enteral feeds and adding fortification decreased from 3.4 to 2.3 days. Full enteral feeds were achieved on average 2 days earlier. Birth weight was regained at around 10.2 days of life before the guideline was implemented and at a mean of 9.6 days after the guideline. There was no increase in cases of CLABSI or diagnoses of NEC. CONCLUSION: After implementation of this feeding QI initiative at a level 4 neonatal intensive care unit, central line duration and PN use were decreased and infants reached full enteral feeds earlier without changes in cases of NEC, CLABSI, or time to regain birth weight.

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.

Survey of ECMO practices for infants with hypoxic ischemic encephalopathy.

OBJECTIVE: Historically, some physicians are reluctant to offer extracorporeal membrane oxygenation (ECMO) to infants with neonatal encephalopathy. This study describes how ECMO practices have changed since the development of therapeutic hypothermia (TH) for neonatal encephalopathy. STUDY DESIGN: A 22-question electronic survey was sent to neonatal medical directors and ECMO directors in the USA and Canada. Participants were queried on TH and ECMO practices and if they would offer ECMO given certain clinical factors; confidential responses were compared with a similar survey conducted in 2008. RESULT: A total of 356 physicians were invited to participate, and the response rate was 25%. Seventy-two percent had initiated or referred for ECMO during cooling therapy. Compared with the 2008 survey, participants were more likely to offer ECMO for moderate and severe encephalopathy. Ninety-four percent offer hypothermia for neonatal encephalopathy, but only 24% have written ECMO criteria for such patients. Neonatologists were more likely than non-neonatologists to offer ECMO for mild and moderate encephalopathy. CONCLUSION: ECMO use with neonatal encephalopathy has increased since TH has become standard care. Wide variability in practice remains with important differences between neonatologists and non-neonatologists.

Characteristics and outcomes of very low birth weight infants receiving epinephrine during delivery room resuscitation.

BACKGROUND: Delivery room resuscitation of very low birth weight infants can involve use of endotracheal or intravenous epinephrine. Data of the past 19 years were reviewed to identify the usage of epinephrine in delivery room and identify characteristics of these babies. METHODS: Neonates with ≤1500g birthweight from January 1996 to August 2014 were reviewed. Infants born alive and admitted to NICU were eligible. Characteristics such as demographics, survival and outcomes were recorded. Variables significant at p≤0.1 among neonates receiving epinephrine were further analyzed via multiple logistic regressions. RESULTS: Out of 5868 eligible neonates, 416 (7%) received epinephrine in the delivery room. The infants who received epinephrine were of lower estimated gestational age (25 vs. 28wk) and lower birth weight (746 vs. 980g). Gender, race and mode of delivery were comparable between the two cohorts. Survival was higher in non-epinephrine group (89.4 vs. 61.1%). Bacterial infection (24.3 vs. 18.4%) and combined grade 3 and 4 intraventricular hemorrhage (18.4 vs. 8.4%) were higher in epinephrine group. Use of epinephrine in the delivery room was associated with decreased survival even after controlling for birth weight, gestational age and low Apgar scores [Odd ratio - 0.48 with 95% CI (0.37-0.62), p<0.001]. CONCLUSION: Neonates with lower birth weight and younger gestational age were more likely to receive epinephrine during resuscitation at birth. Use of epinephrine in delivery room was associated with lower survival and severe intraventricular hemorrhage among very low birth weight infants.

Combination therapy with ampicillin and azithromycin improved outcomes in a mouse model of group B streptococcal sepsis.

BACKGROUND: Evidence suggests that ß-lactam monotherapy of streptococcal infections may incite stronger inflammation and is inferior to combination therapy with macrolides. We hypothesized that use of macrolides alone or in combination with a ß-lactam for group B streptococcal (GBS) sepsis would improve outcomes by reducing inflammation. METHODS: TNF-α was measured from supernatants of RAW 264.7 cells stimulated with GBS isolates, in presence of four treatment regimens: ampicillin alone, azithromycin alone, or combination of azithromycin plus ampicillin. Mouse model of GBS sepsis was developed and treated with same four regimens. Clinical sepsis scores were monitored; serum cytokines (TNF-α, IL-6, IL-10) and chemokines (MIP-1α) were measured at the end. RESULTS: GBS isolates exposed to azithromycin or combination (compared to ampicillin alone) stimulated less TNF production in vitro. In the murine sepsis model, mortality was lower along with decreased sepsis scores in mice treated with combination therapy. Mean serum IL-6 was lower in mice treated with azithromycin alone (66±52 pg/ml) or combination of ampicillin plus azithromycin (52±22 pg/ml) compared to ampicillin alone (260±160 pg/ml) (p<0.005). CONCLUSIONS: Combination therapy of ampicillin+azithromycin improved outcomes in a murine GBS sepsis model; this therapeutic approach deserves additional study.