Cue-Based Feeding as Intervention to Achieve Full Oral Feeding in Preterm Infants Primarily Managed with Bubble CPAP.

OBJECTIVE: Cue-based feeding aims at matching introduction of per oral (PO) feeding with physiological readiness of preterm infants to facilitate PO intake and avoid oral aversion. It was claimed that cue-based feeding may lead to delay in the initiation or achieving full PO feeding in clinical setting primarily using bubble nasal continuous positive airway pressure (CPAP). The study aimed to examine the association of cue-based feeding with time of introduction and completing oral feeding in infants primarily managed with bubble CPAP. STUDY DESIGN: A retrospective analysis where outcomes of preterm infants ≤32 weeks' gestational age (GA) and ≤2,000 g birth weight (BW) were compared after a practice change from volume-based feeding advancement to cue-based feeding. Continuous variables were compared by using t-test and multilinear regression analysis to control for confounding variables. RESULTS: Of the 311 preterm infants who met inclusion and exclusion criteria, 194 were in the cue-based feeding group and 117 were in the volume-based advancement historical comparison group. There were no differences between groups regarding demographic or clinical variables. Postmenstrual age (PMA) of initial feeding assessment was less in the cue-based feeding group. Age of first PO feeding and when some PO was achieved every feed was mildly delayed in the cue-based feeding compared with comparison group, 34 (±1.3) versus 33.7 (±1.2) weeks, and 36.2 (±2.3) versus 36.0 (±2.4) weeks, (p < 0.01) respectively. However, the age of achieving full PO did not differ between groups, 36.8 (±2.2) versus 36.4 (±2.4) weeks (p = 0.13). There was no difference between groups regarding growth parameters at 36 weeks' PMA or at discharge. Similar results were obtained when examining subcategories of infants ≤1,000 g and 1,001 to 2,000 g. CONCLUSION: Cue-based feeding may not be associated with a delay in achieving full oral feeding or prolongation of the length of stay in preterm infants managed with CPAP. KEY POINTS: · Cue-based feeding matches introduction of PO feeding with physiological readiness.. · Cue-based feeding may not be associated with a delay in achieving full oral feeding in preterm infants.. · Cue-based feeding is not associated with prolongation of the length of stay in preterm infants.. · Cue based feeding in preterm infants managed with noninvasive bubble CPAP is examined..

Length of Neuromuscular Re-education Therapy and Growth Parameters in Premature Infants.

OBJECTIVE: Neuromuscular re-education (NMRE) therapy including bracing, containment, facilitation techniques, joint compression, weight (WT) bearing, and myofascial release has been shown to improve neurodevelopmental maturation in premature infants. This study aimed to examine the association of NMRE with growth parameters including WT and length (L) at 36 weeks postmenstrual age (PMA) and at discharge. STUDY DESIGN: We analyzed data of infants <34 weeks gestational age (GA) or <1,800 g birth weight (BW) to examine the association of NMRE with growth parameters using correlation coefficient analysis. The effect of potential confounders was examined using multilinear regression models. RESULTS: Study includes 253 premature infants. Average GA was 300/7 weeks (±23/7) and BW was 1,315 g (±416), 49.8% were females and 65% were African Americans. NMRE has inverse correlation with WT at birth and at 36 weeks PMA, -0.66 (<0.001) and -0.21 (<0.001), respectively, but not at the time of discharge. NMRE has direct correlation with change in WT from birth to 36 weeks PMA and time of discharge, 0.50 (<0.001) and 0.62 (<0.001), respectively, and from the time of starting therapy to 36 weeks PMA or discharge, 0.25 (<0.001) and 0.51 (<0.001), respectively. There was no negative correlation between NMRE with daily WT gain from birth to 36 weeks PMA or to discharge, -0.05 (0.43) and -0.07 (0.23), respectively, or from the time of starting therapy to 36 weeks PMA, -0.09 (0.14). There was an inverse correlation between NMRE with average WT gain per day from the time of starting therapy to discharge, -0.26 (<0.001), Similar findings were found examining the correlation between NMRE and changes in L. Multilinear regression analysis examining the relationship while controlling for GA, BW, sex, and race; socioeconomic variables; and concurrent massage therapy and sensory integration revealed similar results. CONCLUSION: NMRE, aimed to enhance neurodevelopmental outcomes of premature infants, may not have a negative impact on their physical growth. KEY POINTS: · NMRE has been introduced in the care of premature infants to improve neurodevelopmental outcomes.. · It was hypothesized that NMRE may cause stress and lead to failure to thrive or suboptimal growth.. · The association of the duration of NMRE with length and weight gain in very low birth weight infants was examined, and there was no negative correlation..

A Dose-Limited Dexamethasone and Bubble Continuous Positive Airway Pressure in Ventilation-Dependent Extremely Premature Infants.

OBJECTIVE: Dexamethasone has been associated with early extubation and shorter duration of mechanical ventilation in preterm infants. High doses or prolonged courses of dexamethasone may be associated with poor neurodevelopmental outcomes. STUDY DESIGN: This is an observational cohort study assessing the efficacy of a low-dose short dexamethasone course combined with postextubation bubble continuous positive airway pressure (bCPAP) strategy on rates of successful extubation and reduction of the duration of invasive mechanical ventilation in extremely preterm infants. We compared the short-term outcomes of implementing such strategy on a group of infants with birth weight <750 g to a historical cohort. RESULTS: Among infants intubated for at least 10 days, median time to extubation from starting the dexamethasone course was 2 days (interquartile range: 1-3). Total duration of intubation was significantly shorter in infants who received dexamethasone compared with the control groups (21 ± 6 vs. 30 ± 10 days, p = 0.03), and although statistically nonsignificant, duration to wean to 21% bCPAP was shorter compared with the control group (48 ± 13 vs. 74 ± 29 days, p = 0.06). CONCLUSION: A low-dose short dexamethasone course combined with postextubation bCPAP intervention may be associated with successful early extubation and shorter duration of mechanical ventilation. KEY POINTS: · Noninvasive strategies may not succeed in infants < 750 g birth weight.. · Bubble CPAP has been shown to be associated with reduced complications including chronic lung disease.. · Postnatal dexamethasone therapy may succeed in conjunction with bubble CPAP to reduce reintubation..

Maternal Opioids Usage and Cesarean Delivery Rates: A Retrospective Cross-Sectional Analysis.

OBJECTIVE: The growing opioid crisis increasingly affects maternal care in the US and it is unknown if opioid use puts pregnant women at increased odds for cesarean delivery (CD). Understanding how opioids influence CD trends is important in improving maternal and neonatal outcomes. This study aims to understand the association of opioid use with CD in the context of the demographic, clinical, behavioral, and health system complexity. METHODS: This retrospective cross-sectional analysis used representative data from the 2012-2014 National Inpatient Sample. Opioid use during pregnancy, CD, and other clinical variables were identified using ICD9 codes. Characteristics were assessed using bivariate and multivariate statistics. A logistic regression model was used to determine the association between opioid use and CD while controlling for confounders. Adjustments were made for rural/urban hospital location, regional median income, maternal age, race, and medical and pregnancy-related conditions. RESULTS: The rate of CD in the overall sample was about 30%. Among opioids-users, the overall proportion of CD was significantly less (24.7%). The adjusted odds ratio for CD among opioids users was 0.74 (CI: 0.73-0.76, p < 0.001). This finding is unique to pregnant women who are covered by public insurance. In rural areas, the relationship between opioid use and CD was not significant. CONCLUSION: Opioid use during pregnancy is associated with lower CD rates in urban settings. This evidence suggests that maternal care varies between rural and urban areas in relation to CD of pregnant opioid users compared to non-opioid users.

Hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non-alcoholic steatohepatitis.

BACKGROUND: Hepatic expression of Sonic Hedgehog (SHH) is associated with Non-alcoholic fatty liver disease (NAFLD) and development of Non-alcoholic steatohepatitis (NASH). Hepatic SHH detection increases with the diagnosis of NASH. This pilot study was designed to confirm that staining for SHH is useful in NASH diagnosis and determine whether quantification of staining by computer assisted morphometry (CAM) can be used to assess severity of ballooning degeneration. METHODS: SHH was detected by immunohistochemistry (IHC) on paraffin-embedded liver sections in subjects (N = 69) with biopsy proven NAFLD and no liver disease (control). Serum samples were also available for these subjects. Post-staining, a digitized image of the section was acquired and an area quantification algorithm was used to quantify the degree of SHH expression. Additionally, circulating M30, M65, and SHH were measured by ELISA. RESULTS: Notably, hepatic SHH expression correlated with histologic ballooning degeneration (rho = 0.62, p < 0.0001), steatosis grade (rho = 0.554, P < 0.001), Mallory-Denk bodies (rho = 0.54, P < 0.001), pericellular fibrosis (rho = 0.527, P < 0.001), and lymphocytic infiltration (rho = 0.435, P < 0.0002). Additionally, hepatic SHH expression correlated with circulating M65 (rho = 0.588, p < 0.0001), and circulating M30 (rho = 0.375, p = 0.001), as well as AST and ALT (rho = 0.43, p = 0.0004, and rho = 0.27, p = 0.03, respectively). Further, serum M30 was almost twice as high in NASH patients compared to non-NASH (539.1 ± 290.8 U/L vs. 287.6 ± 190.5 U/L; p = 0.0002), while M65 was almost three times higher in NASH patients compared to non-NASH (441.2 ± 464.2 U/L vs. 162.8 ± 353.1 U/L, P = 0.0006). Logistic modeling indicates hepatic SHH expression and presence of type 2 diabetes as independent predictors of advanced fibrosis (defined as portal and pericellular fibrosis > 2: OR = 1.986, p = 0.01, and OR = 3.280, p = 0.03, respectively). CONCLUSION: Thus, our findings show quantitation of SHH expression by CAM can provide a tool for quantifying changes in hepatocyte injury and assist in unambiguous staging/grading of NASH. Our study showed minimal interobserver variability using CAM based quantification. Once validated, CAM assessment of hepatic SHH could benefit clinical trials or long term outcomes studies of NASH subjects.

An exploratory study examining how nano-liquid chromatography-mass spectrometry and phosphoproteomics can differentiate patients with advanced fibrosis and higher percentage collagen in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is among the leading causes of liver disease worldwide. It is increasingly recognized that the phenotype of NASH may involve a number of different pathways, of which each could become important therapeutic targets. The aim of this study is to use high resolution mass spectrometry (MS) and phosphoproteomics techniques to assess the serum proteome and hepatic phosphoproteome in subjects with NASH-related fibrosis. METHODS: Sixty-seven biopsy-proven NAFLD subjects with frozen sera and liver tissue were included. Reverse phase protein microarray was used to quantify the phosphorylation of key signaling proteins in liver and nano-liquid chromatography (LC)-MS was used to sequence target biomarkers in the serum. An image analysis algorithm was used to quantify the percentage of collagen (% collagen) using computer-assisted morphometry. Using multiple regression models, serum proteomes and phosphorylated hepatic proteins that were independently (p ≤ 0.05) associated with advanced fibrosis (stage ≥ 2) and higher % collagen were assessed. RESULTS: Phosphorylated signaling pathways in the liver revealed that apoptosis signal-regulating kinase 1, mitogen-activated protein kinase (ASK1-MAPK pathway involving ASK1 S38 (p < 0.02) and p38 MAPK (p = 0.0002)) activated by the inflammatory cytokine interleukin (IL-10) (p < 0.001), were independently associated with higher % collagen. LC-MS data revealed that serum alpha-2 macroglobulin (α2M) (p = 0.0004) and coagulation factor V (p = 0.0127) were independently associated with higher % hepatic collagen. CONCLUSIONS: Simultaneous profiling of serum proteome and hepatic phosphoproteome reveals that the activation of ASK1 S38, p38 MAPK in the liver, and serum α2M and coagulation factor V are independently associated with hepatic collagen deposition in patients with NASH. These data suggest the role of these pathways in the pathogenesis of NASH-related fibrosis as a potential therapeutic target.

Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver disease worldwide. We estimated the global prevalence, incidence, progression, and outcomes of NAFLD and nonalcoholic steatohepatitis (NASH). PubMed/MEDLINE were searched from 1989 to 2015 for terms involving epidemiology and progression of NAFLD. Exclusions included selected groups (studies that exclusively enrolled morbidly obese or diabetics or pediatric) and no data on alcohol consumption or other liver diseases. Incidence of hepatocellular carcinoma (HCC), cirrhosis, overall mortality, and liver-related mortality were determined. NASH required histological diagnosis. All studies were reviewed by three independent investigators. Analysis was stratified by region, diagnostic technique, biopsy indication, and study population. We used random-effects models to provide point estimates (95% confidence interval [CI]) of prevalence, incidence, mortality and incidence rate ratios, and metaregression with subgroup analysis to account for heterogeneity. Of 729 studies, 86 were included with a sample size of 8,515,431 from 22 countries. Global prevalence of NAFLD is 25.24% (95% CI: 22.10-28.65) with highest prevalence in the Middle East and South America and lowest in Africa. Metabolic comorbidities associated with NAFLD included obesity (51.34%; 95% CI: 41.38-61.20), type 2 diabetes (22.51%; 95% CI: 17.92-27.89), hyperlipidemia (69.16%; 95% CI: 49.91-83.46%), hypertension (39.34%; 95% CI: 33.15-45.88), and metabolic syndrome (42.54%; 95% CI: 30.06-56.05). Fibrosis progression proportion, and mean annual rate of progression in NASH were 40.76% (95% CI: 34.69-47.13) and 0.09 (95% CI: 0.06-0.12). HCC incidence among NAFLD patients was 0.44 per 1,000 person-years (range, 0.29-0.66). Liver-specific mortality and overall mortality among NAFLD and NASH were 0.77 per 1,000 (range, 0.33-1.77) and 11.77 per 1,000 person-years (range, 7.10-19.53) and 15.44 per 1,000 (range, 11.72-20.34) and 25.56 per 1,000 person-years (range, 6.29-103.80). Incidence risk ratios for liver-specific and overall mortality for NAFLD were 1.94 (range, 1.28-2.92) and 1.05 (range, 0.70-1.56). CONCLUSIONS: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous. (Hepatology 2016;64:73-84).

Acceptability of intramuscular injection of tranexamic acid in postpartum hemorrhage prevention.

BACKGROUND: Newer research comparing routes of medication administration has extended beyond efficacy as a primary endpoint to incorporate patient preference. However, little is known about the preferences of pregnant women in terms of routes of medication administration, specifically with regards to hemorrhage prevention and control. OBJECTIVE: This study aimed to understand the preferences of pregnant women in terms of medical interventions to prevent hemorrhage at the time of delivery. STUDY DESIGN: Surveys were distributed from April 2022 to September 2022 using electronic tablets at a single urban center with an annual delivery volume of 3000 women per year to women >18 years of age who were either currently pregnant or have been pregnant in the past. Subjects were asked to choose their preferred route of administration from the following options: intravenous, intramuscular, or subcutaneous. The primary outcome was patient preference on the route of medication administration during a hemorrhage event. RESULTS: The study cohort included 300 patients, mostly African American (39.8%) followed by White (32.1%), and the majority of the participants ranged from 30 to 34 years of age (31.7%). When asked which method of administration they would prefer to prevent hemorrhage before birth, the results were as follows: 31.1% would prefer intravenous, 23.0% had no preference, 21.2% were unsure, 15.9% preferred subcutaneous, and 8.8% preferred intramuscular administration. In addition, 69.4% of respondents reported that they have never declined or avoided intramuscular administration of medication if recommended by their physician. CONCLUSION: Although some survey participants preferred an intravenous route of administration, 68.9% of subjects were unsure, had no preference, or preferred nonintravenous routes. This information is helpful particularly in low-resource settings where intravenous treatments are not readily available or in urgent clinical situations in which intravenous administration routes are not easily obtainable in high-risk patients.

Antenatal magnesium sulfate and the need for mechanical ventilation in the first three days of life.

BACKGROUND: Antenatal administration of magnesium sulfate (MgSO4) to women in preterm labor has gained widespread use. This study examined the relationship between MgSO4 exposure with neonatal respiratory outcomes. METHODS: Very low birth weight (VLBW) infants exposed to antenatal MgSO4 were included. Infants who were intubated anytime during the first three days of life were compared to those who were not intubated regarding their demographic and clinical characteristics, MgSO4 therapy, immediate respiratory outcomes, and occurrence of intraventricular hemorrhage (IVH) using student t-test, chi square testing and logistic regression analysis to control for confounding variables. Correlation coefficient of MgSO4 cumulative dose given and duration of infusion with delivery room resuscitation and need for mechanical ventilation in the first 3 days of life were also calculated. Multilinear regression analysis was used to control for confounding factors. RESULTS: Intubated group included 96 infants while non-intubated group included 171 infants. Although, intubated group has younger gestational age (26 vs. 29 weeks, p < 0.01) and lower birth weight (786 vs. 1115 g (g), p < 0.01), there were no significant differences between groups in regard to MgSO4 cumulative dose (24 vs. 27 g, p = 0.29), infusion time (14.6 vs. 18 h, p = 0.19) or infants' serum magnesium level (2.6 vs. 2.8 milliequivalents (mEq)/L p = 0.86). There was no correlation between cumulative MgSO4 dose with endotracheal intubation or cardiac resuscitation in the delivery room (cc: -0.03, p = 0.66; and 0.02, p = 0.79, respectively) or the need for mechanical ventilation in the first 3 days of life (cc: -0.04 to -0.07, p = 0.21-0.51). In addition, there was no relationship between MgSO4 dose, duration of infusion, or infant's serum magnesium level and occurrence of IVH. CONCLUSION: Regardless of dose or duration of infusion, antenatal MgSO4 exposure is not associated with increased intubation or mechanical ventilation early in life.

The impact of a multifaceted quality improvement program on the incidence of necrotizing enterocolitis in very low birth weight infants.

BACKGROUND: Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease which mostly occurs in very low birth weight (VLBW) infants. In addition to decreasing gestational age (GA) or birth weight (BW), artificial formula, delayed initiation or rapidly advanced feeding, severe anemia and systemic infections were associated with NEC. Several studies demonstrated that breast milk, standardized feeding advancement regimens and treatment of anemia are associated with less incidence of NEC. It is not known if including all these interventions in one multifaceted program will lead to significant reduction in NEC. METHODS: The NICU team at The George Washington University Hospital created a multifaceted interdisciplinary quality improvement project to tackle several aspects of NEC prevention that addressed researched risk factors for NEC. The program was made of four quality improvement protocols: 1) Standardized Structured Feeding Program, 2) Feeding Intolerance Management Algorithm, 3) Enteral Osmolality Control Tool, and 4) Packed Red Blood Cell (RBC) Standardized Transfusion Protocol. This time-series, quasi experimental study design examined the differences in the incidence of NEC between infants with BW < 1500 g who were admitted to the GW Hospital NICU before and after the program implementation. RESULTS: Data from 408 VLBW infants were included in the study. Although not statistically significant, there was a decreasing trend of NEC incidence in the post-implementation group (n = 199) compared to the pre-implementation group (n = 209), (3.5% vs. 5.3%, p = 0.88). The trend in the incidence of NEC declined further after the introduction of RBC transfusion protocol which was introduced ten month after starting the other elements of the program. CONCLUSION: Integration of the multifaceted quality improvement program may be associated with a decline in the occurrence of NEC. Further analysis with a larger sample size is required to determine if the changes seen are statistically significant.

Major Histocompatibility Complex Class I-Related Chain A Alleles and Histology of Nonalcoholic Fatty Liver Disease.

Major histocompatibility complex class I-related chain A (MICA) is a highly polymorphic gene that modulates immune surveillance by binding to its receptor on natural killer cells, and its genetic polymorphisms have been associated with chronic immune-mediated diseases. The progressive form of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), is characterized by accumulation of fat and inflammatory cells in the hepatic parenchyma, potentially leading to liver cell injury and fibrosis. To date, there are no data describing the potential role of MICA in the pathogenesis of NAFLD. Therefore, our aim was to assess the association between MICA polymorphism and NASH and its histologic features. A total of 134 subjects were included. DNA from patients with biopsy-proven NAFLD were genotyped using polymerase chain reaction-sequence-specific oligonucleotide for MICA alleles. Liver biopsies were assessed for histologic diagnosis of NASH and specific pathologic features, including stage of fibrosis and grade of inflammation. Multivariate analysis was performed to draw associations between MICA alleles and the different variables; P ≤ 0.05 was considered significant. Univariate analysis showed that MICA*011 (odds ratio [OR], 7.14; 95% confidence interval [CI], 1.24-41.0; P = 0.04) was associated with a higher risk for histologic NASH. Multivariate analysis showed that MICA*002 was independently associated with a lower risk for focal hepatocyte necrosis (OR, 0.24; 95% CI, 0.08-0.74; P = 0.013) and advanced fibrosis (OR, 0.11; 95% CI, 0.02-0.70; P = 0.019). MICA*017 was independently associated with a higher risk for lymphocyte-mediated inflammation (OR, 5.12; 95% CI, 1.12-23.5; P = 0.035). Conclusion: MICA alleles may be associated with NASH and its histologic features of inflammation and fibrosis. Additional research is required to investigate the potential role of MICA in increased risk or protection against NAFLD.