Evaluating the Utility of Diagnostic Workups for Biliary Atresia in Neonates with Cholestatic Jaundice Following Prolonged TPN

Introduction: Parenteral nutrition associated cholestasis (PNAC) develops in 40-60% of premature infants following TPN for 2-4+ weeks. The incidence of biliary atresia is low and there is a 60-day, post-term window for corrective surgery. There is limited data on both the natural history of PNAC in premature infants following prolonged TPN, as well as the utility of diagnostic tools investigating biliary atresia in these patients. Methods: A retrospective chart review using EMR data from the Intensive Care Nursey was performed with the following criteria: premature babies diagnosed with cholestasis, born at \u3c1500 grams, and received TPN for 14 days. Ultimately 61 babies met criteria and data was collected and pooled to produce descriptive statistics and graphs describing laboratory trends. Results: Median gestational age was 26 [IQR 25, 28] weeks, birth weight was 732 [650, 930] grams and 60% (36/60) were male. After being on TPN for a median of 51 [38, 73] days and developing cholestasis, 12/61 (19.7%) babies underwent hepatobiliary scintigraphy, three of which also underwent repeat scans, 29/61 (47.5%) received GI consults and 32/61 (52.5%) underwent abdominal ultrasounds. No babies were diagnosed with biliary atresia. Graphical depiction of laboratory trends demonstrates an initial spike in direct bilirubin after TPN cessation, followed by a gradual decline 3-4 weeks later. Discussion: Despite many diagnostic procedures and consults, PNAC was the only observed diagnosis at discharge for this cohort of babies. Based on the laboratory trends, delaying the investigation of elevated bilirubin until 3-4 weeks after ceasing TPN might prevent unnecessary diagnostics and improve resource allocation

Effects of Neonatal Abstinence Syndrome on Long-Term Growth Parameters

Introduction: Past studies have shown that babies with Neonatal Abstinence Syndrome (NAS) have lower weight, head circumference, and height at birth. This study aims to compare their growth at 9 and 18 months of age, and to compare growth parameter of NAS infants below 10th percentile to those above 10th percentile at birth. Methods: In this retrospective review, 260 infants admitted to Jefferson Neonatal Intensive Care Unit between 2006 and 2018 were included. The weight, height, and head circumference at birth, 9 months, and 18 months were collected and correlated by Pearson correlation. The growth parameters of infants below 10th percentile at birth were also compared with those above 10th percentile by appropriate statistical tests. Results: There was a significant but weak correlation between birth and 9 month weight, head circumference, and length (r=0.28, p \u3c 0.001; r=0.22, p = 0.001; and r=0.13, p = 0.048; respectively) which persisted at 18 months for weight and head circumference but not for length. There were significant differences in weight (p = 0.01), head circumference (p = 0.02), and length (p = 0.02) between infants below 10th percentile and those above 10th percentile at 9 months, but not at 18 months. Discussion: The results implicate that NAS infants who were small for gestational age at birth catch up to their counterparts in physical growth parameter. Further studies on longer term follow-up and underlying factors that allow for this growth could help design interventions that enhance their growth

Lung Rest During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure-Practice Variations and Outcomes.

OBJECTIVE: Describe practice variations in ventilator strategies used for lung rest during extracorporeal membrane oxygenation for respiratory failure in neonates, and assess the potential impact of various lung rest strategies on the duration of extracorporeal membrane oxygenation and the duration of mechanical ventilation after decannulation. DATA SOURCES: Retrospective cohort analysis from the Extracorporeal Life Support Organization registry database during the years 2008-2013. STUDY SELECTION: All extracorporeal membrane oxygenation runs for infants less than or equal to 30 days of life for pulmonary reasons were included. DATA EXTRACTION: Ventilator type and ventilator settings used for lung rest at 24 hours after extracorporeal membrane oxygenation initiation were obtained. DATA SYNTHESIS: A total of 3,040 cases met inclusion criteria. Conventional mechanical ventilation was used for lung rest in 88% of cases and high frequency ventilation was used in 12%. In the conventional mechanical ventilation group, 32% used positive end-expiratory pressure strategy of 4-6 cm H2O (low), 22% used 7-9 cm H2O (mid), and 43% used 10-12 cm H2O (high). High frequency ventilation was associated with an increased mean (SEM) hours of extracorporeal membrane oxygenation (150.2 [0.05] vs 125 [0.02]; p \u3c 0.001) and an increased mean (SEM) hours of mechanical ventilation after decannulation (135 [0.09] vs 100.2 [0.03]; p = 0.002), compared with conventional mechanical ventilation among survivors. Within the conventional mechanical ventilation group, use of higher positive end-expiratory pressure was associated with a decreased mean (SEM) hours of extracorporeal membrane oxygenation (high vs low: 136 [1.06] vs 156 [1.06], p = 0.001; mid vs low: 141 [1.06] vs 156 [1.06]; p = 0.04) but increased duration of mechanical ventilation after decannulation in the high positive end-expiratory pressure group compared with low positive end-expiratory pressure (p = 0.04) among survivors. CONCLUSIONS: Wide practice variation exists with regard to ventilator settings used for lung rest during neonatal respiratory extracorporeal membrane oxygenation. Use of high frequency ventilation when compared with conventional mechanical ventilation and use of low positive end-expiratory pressure strategy when compared with mid positive end-expiratory pressure and high positive end-expiratory pressure strategy is associated with longer duration of extracorporeal membrane oxygenation. Further research to provide evidence to drive optimization of pulmonary management during neonatal respiratory extracorporeal membrane oxygenation is warranted

Adverse Events Following Screening Eye Examinations for Retinopathy of Prematurity in Premature Infants

Introduction: The retinopathy of prematurity (ROP) examination is recommended for high-risk preterm infants to prevent its complications but may be associated with adverse events. The goal of this study is to determine whether the ROP examination increases the incidence of adverse events in premature infants. Design/Methods: This was a retrospective study on all preterm infants (32 weeks gestation) born between 03/2017 and 12/2019 who survived until the first eye examination. The number of episodes of apnea (A), bradycardia (B), desaturation (D), number of infants on mechanical ventilation, and number of infants requiring sepsis evaluation were compared before and after the eye examination. The groups were compared using paired t-test, chi-square, ANOVA, and extended Fisher’s Exact test. Results: 124 infants met the study criteria and 461 examinations were performed. There was no significant difference in ABD 1 day before, on the day of examination, and one day after the examination. There was a significant difference in either A, B or D 3 days before and 3 days after an eye examination (p=0.04) but not in cumulative adverse events. There was no significant difference in the number of infants on mechanical ventilation or requiring sepsis evaluation before and after the examination. Conclusions: ROP examination was not associated with increased adverse events. Isolated finding of an increase in A/B/D 3 days after examination could be due to multiple comparison. These findings are useful for clinicians to consider when screening for ROP in vulnerable neonates

Reduced maternal immunity and vertical transfer of immunity against SARS-CoV-2 variants of concern with COVID-19 exposure or initial vaccination in pregnancy.

INTRODUCTION: As the SARS-CoV-2 pandemic continues to evolve, we face new variants of concern with a concurrent decline in vaccine booster uptake. We aimed to evaluate the difference in immunity gained from the original SARS-CoV-2 mRNA vaccine series in pregnancy versus SARS-CoV-2 exposure during pregnancy against recent variants of concern. STUDY DESIGN: This is a retrospective analysis of previously collected samples from 192 patients who delivered between February 2021 and August 2021. Participants were categorized as 1) COVID vaccine: mRNA vaccine in pregnancy, 2) COVID-exposed, and 3) controls. The primary outcome was neutralizing capacity against wild-type, Delta, and Omicron-B1 between cohorts. Secondary outcomes include a comparison of cord-blood ID50 as well as the efficiency of vertical transfer, measured by cord-blood:maternal blood ID50 for each variant. RESULTS: Pregnant women with COVID-19 vaccination had a greater spike in IgG titers compared to both those with COVID-19 disease exposure and controls. Both COVID exposure and vaccination resulted in immunity against Delta, but only COVID vaccination resulted in significantly greater Omicron ID-50 versus controls. The neutralizing capacity of serum from newborns was lower than that of their mothers, with COVID-vaccination demonstrating higher cord-blood ID50 vs wildtype and Delta variants compared to control or COVID-exposed, but neither COVID-exposure nor vaccination demonstrated significantly higher Omicron ID50 in cord-blood compared to controls. There was a 0.20 (0.07-0.33, p=0.004) and 0.12 (0.0-0.24, p=0.05) increase in cord-blood:maternal blood ID50 with COVID vaccination compared to COVID-19 exposure for wild-type and Delta respectively. In pair-wise comparison, vertical transfer of neutralization capacity (cord-blood:maternal blood ID50) was greatest for wild-type and progressively reduced for Delta and Omicron ID50. CONCLUSION: Pregnant patients with either an initial mRNA vaccination series or COVID-exposure demonstrated reduced immunity against newer variants compared to wild-type as has been reported for non-pregnant individuals; however, the COVID-vaccination series afforded greater cross-variant immunity to pregnant women, specifically against Omicron, than COVID-disease. Vertical transfer of immunity is greater in those with COVID vaccination vs COVID disease exposure but is reduced with progressive variants. Our results reinforce the importance of bivalent booster vaccination in pregnancy for both maternal and infant protection and also provide a rationale for receiving updated vaccines as they become available

Gender variations in neonatal and early infant mortality in India and Pakistan: A secondary analysis from the global network maternal newborn health registry

Background: To determine the gender differences in neonatal mortality, stillbirths, and perinatal mortality in south Asia using the Global Network data from the Maternal Newborn Health Registry.Methods: This study is a secondary analysis of prospectively collected data from the three south Asian sites of the Global Network. The maternal and neonatal demographic, clinical characteristics, rates of stillbirths, early neonatal mortality (1-7 days), late neonatal mortality (8-28 days), mortality between 29-42 days and the number of infants hospitalized after birth were compared between the male and female infants.Results: Between 2010 and 2018, 297,509 births [154,790 males (52.03%) and 142,719 females (47.97%)] from two Indian sites and one Pakistani site were included in the analysis [288,859 live births (97.1%) and 8,648 stillbirths (2.9%)]. The neonatal mortality rate was significantly higher in male infants (33.2/1,000 live births) compared to their female counterparts (27.4/1,000, p \u3c 0.001). The rates of stillbirths (31.0 vs. 26.9/1000 births) and early neonatal mortality (27.1 vs 21.6/1000 live births) were also higher in males. However, there were no significant differences in late neonatal mortality (6.3 vs. 5.9/1000 live births) and mortality between 29-42 days (2.1 vs. 1.9/1000 live births) between the two groups. More male infants were hospitalized within 42 days after birth (1.8/1000 vs. 1.3/1000 live births, p \u3c 0.001) than females.Conclusion: The risks of stillbirths, and early neonatal mortality were higher among male infants than their female counterparts. However, there was no gender difference in mortality after 7 days of age. Our results highlight the importance of stratifying neonatal mortality into early and late neonatal period to better understand the impact of gender on neonatal mortality. The information from this study will help in developing strategies and identifying measures that can reduce differences in sex-specific mortality

A novel noninvasive approach for evaluating work of breathing indices in a developmental rat model using respiratory inductance plethysmography.

Pulmonary function testing (PFT) is an important component for evaluating the outcome of experimental rodent models of respiratory diseases. Respiratory inductance plethysmography (RIP) provides a noninvasive method of PFT requiring minimal cooperation. RIP measures work of breathing (WOB) indices including phase angle (Ф), percent rib cage (RC %), breaths per minute (BPM), and labored breathing index (LBI) on an iPad. The aim of this study was to evaluate the utility of a recently developed research instrument, pneuRIP, for evaluation of WOB indices in a developmental rat model. Sprague Dawley rats (2 months old) were commercially acquired and anaesthetised with isoflurane. The pneuRIP system uses two elastic bands: one band (RC) placed around the rib cage under the upper armpit and another band (AB) around the abdomen. The typical thoracoabdominal motion (TAM) plot showed the abdomen and rib cage motion in synchrony. The plots of phase angle and LBI as a function of data point number showed that values were within the range. The distribution for phase angle and LBI was within a narrow range. pneuRIP testing provided instantaneous PFT results. This study demonstrated the utility of RIP as a rapid, noninvasive approach for evaluating treatment interventions in the rodent model

The Airway Microbiome at Birth.

Alterations of pulmonary microbiome have been recognized in multiple respiratory disorders. It is critically important to ascertain if an airway microbiome exists at birth and if so, whether it is associated with subsequent lung disease. We found an established diverse and similar airway microbiome at birth in both preterm and term infants, which was more diverse and different from that of older preterm infants with established chronic lung disease (bronchopulmonary dysplasia). Consistent temporal dysbiotic changes in the airway microbiome were seen from birth to the development of bronchopulmonary dysplasia in extremely preterm infants. Genus Lactobacillus was decreased at birth in infants with chorioamnionitis and in preterm infants who subsequently went on to develop lung disease. Our results, taken together with previous literature indicating a placental and amniotic fluid microbiome, suggest fetal acquisition of an airway microbiome. We speculate that the early airway microbiome may prime the developing pulmonary immune system, and dysbiosis in its development may set the stage for subsequent lung disease

Reduced maternal immunity and vertical transfer of immunity against SARS-CoV-2 variants of concern with COVID-19 exposure or initial vaccination in pregnancy

IntroductionAs the SARS-CoV-2 pandemic continues to evolve, we face new variants of concern with a concurrent decline in vaccine booster uptake. We aimed to evaluate the difference in immunity gained from the original SARS-CoV-2 mRNA vaccine series in pregnancy versus SARS-CoV-2 exposure during pregnancy against recent variants of concern.Study DesignThis is a retrospective analysis of previously collected samples from 192 patients who delivered between February 2021 and August 2021. Participants were categorized as 1) COVID vaccine: mRNA vaccine in pregnancy, 2) COVID-exposed, and 3) controls. The primary outcome was neutralizing capacity against wild-type, Delta, and Omicron-B1 between cohorts. Secondary outcomes include a comparison of cord-blood ID50 as well as the efficiency of vertical transfer, measured by cord-blood:maternal blood ID50 for each variant.ResultsPregnant women with COVID-19 vaccination had a greater spike in IgG titers compared to both those with COVID-19 disease exposure and controls. Both COVID exposure and vaccination resulted in immunity against Delta, but only COVID vaccination resulted in significantly greater Omicron ID-50 versus controls. The neutralizing capacity of serum from newborns was lower than that of their mothers, with COVID-vaccination demonstrating higher cord-blood ID50 vs wildtype and Delta variants compared to control or COVID-exposed, but neither COVID-exposure nor vaccination demonstrated significantly higher Omicron ID50 in cord-blood compared to controls. There was a 0.20 (0.07-0.33, p=0.004) and 0.12 (0.0-0.24, p=0.05) increase in cord-blood:maternal blood ID50 with COVID vaccination compared to COVID-19 exposure for wild-type and Delta respectively. In pair-wise comparison, vertical transfer of neutralization capacity (cord-blood:maternal blood ID50) was greatest for wild-type and progressively reduced for Delta and Omicron ID50.ConclusionPregnant patients with either an initial mRNA vaccination series or COVID-exposure demonstrated reduced immunity against newer variants compared to wild-type as has been reported for non-pregnant individuals; however, the COVID-vaccination series afforded greater cross-variant immunity to pregnant women, specifically against Omicron, than COVID-disease. Vertical transfer of immunity is greater in those with COVID vaccination vs COVID disease exposure but is reduced with progressive variants. Our results reinforce the importance of bivalent booster vaccination in pregnancy for both maternal and infant protection and also provide a rationale for receiving updated vaccines as they become available

Hyperoxia-Induced miR-195 Causes Bronchopulmonary Dysplasia in Neonatal Mice

Background: Exposure to hyperoxia is an important factor in the development of bronchopulmonary dysplasia (BPD) in preterm newborns. MicroRNAs (miRs) have been implicated in the pathogenesis of BPD and provide a potential therapeutic target. Methods: This study was conducted utilizing a postnatal animal model of experimental hyperoxia-induced murine BPD to investigate the expression and function of miR-195 as well as its molecular signaling targets within developing mouse lung tissue. Results: miR-195 expression levels increased in response to hyperoxia in male and female lungs, with the most significant elevation occurring in 40% O2 (mild) and 60% O2 (moderate) BPD. The inhibition of miR-195 improved pulmonary morphology in the hyperoxia-induced BPD model in male and female mice with females showing more resistance to injury and better recovery of alveolar chord length, septal thickness, and radial alveolar count. Additionally, we reveal miR-195-dependent signaling pathways involved in BPD and identify PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) as a novel specific target protein of miR-195. Conclusions: Our data demonstrate that high levels of miR-195 in neonatal lungs cause the exacerbation of hyperoxia-induced experimental BPD while its inhibition results in amelioration. This finding suggests a therapeutic potential of miR-195 inhibition in preventing BPD