Neonatal inflammation and its association with asthma and obesity in late childhood among individuals born extremely preterm.

BACKGROUND: Asthma and obesity are frequent outcomes among individuals born extremely preterm and are associated with decreased lifespan. Neonatal inflammation is associated with chronic neurodevelopmental disorders; however, it is less studied in association with other later childhood chronic disorders in this population. METHODS: Fourteen hospitals in 5 U.S. states enrolled 1506 infants born before 28 weeks of gestation in the Extremely Low Gestational Age Newborn cohort in 2004-2014. Neonatal blood spots were collected on postnatal days 1, 7, 14, 21, and 28, and used to measure 14 inflammation-related proteins. Associations were evaluated between high (top quartile) levels of proteins and two chronic health disorders at ages 10 and 15 years: physician-diagnosed asthma and obesity (body mass index ≥95th percentile). RESULTS: Few associations were found between high levels of 14 inflammation-related proteins, either on a single day or on multiple days, and either asthma or obesity. Similarly, few associations were found in analyses stratified by sex or presence/absence of prenatal inflammation. CONCLUSIONS: In extremely preterm newborns, systemic elevations of inflammation-related proteins during the neonatal period were not associated with childhood asthma and obesity outcomes at 10 or 15 years of age. IMPACT: In the large multi-center Extremely Low Gestational Age Newborn (ELGAN) cohort, sustained elevation of neonatal levels of inflammation-related proteins was not consistently associated with asthma or obesity outcomes at 10 or 15 years of age. This finding contrasts with reported associations of perinatal inflammation with obesity at 2 years and neurodevelopmental disorders at 2-15 years in the ELGANs, suggesting that unlike neurodevelopment, peripubertal obesity and asthma may be driven by later childhood exposures. Future research on perinatal mechanisms of childhood asthma and obesity should account for both fetal and later exposures and pathways in addition to inflammation at birth.

Early-life determinants of childhood plasma insulin levels: implications for primordial prevention of diabetes.

BACKGROUND: We earlier reported prematurity as an independent risk factor for elevated insulin levels. Investigation is still lacking on the influence of prenatal and perinatal factors on childhood insulin levels. METHODS: In this secondary analysis of a prospective birth cohort, plasma insulin levels were measured at birth and early childhood. Regression models identified early-life factors associated with the primary outcome: log-transformed childhood plasma insulin levels. RESULTS: One thousand one hundred and nine children had insulin levels at birth and 825 at both time points. Compared to term, preterm infants had higher plasma insulin levels (geometric mean) at birth (612, 95% CI 552-679 vs. 372, 95% CI 345-402 pmol/ml) and in early childhood (547, 95% CI 494-605 vs. 445, 95% CI 417-475 pmol/ml). Factors associated with higher early childhood insulin levels included higher insulin level at birth, black race, female sex, maternal smoking during pregnancy, maternal perceived stress, in utero drug exposure, maternal pregestational diabetes mellitus, and maternal preconception overweight and obesity. CONCLUSIONS: In this high-risk US birth cohort, we identified multiple prenatal and perinatal risk factors for higher early childhood insulin levels, in addition to prematurity. These findings lend support to primordial preventive strategies for diabetes mellitus. IMPACT: In this secondary analysis of a large prospective study from a high-risk racially diverse cohort, we identify biological and social factors that contribute to elevated levels of plasma insulin in early childhood. Our study also investigates factors affecting plasma insulin in preterm infants along with comorbidities commonly seen during the neonatal intensive care stay. Our work reaffirms the importance of Developmental Origins of Health and Disease with regards to in utero programming of insulin levels. Our work supports the possibility that primordial preventive strategies for diabetes mellitus in high-risk populations may need to begin as early as the prenatal period.

Childhood obesity and adverse cardiometabolic risk in large for gestational age infants and potential early preventive strategies: a narrative review.

Accumulating evidence indicates that obesity and cardiometabolic risks become established early in life due to developmental programming and infants born as large for gestational age (LGA) are particularly at risk. This review summarizes the recent literature connecting LGA infants and early childhood obesity and cardiometabolic risk and explores potential preventive interventions in early infancy. With the rising obesity rates in women of childbearing age, the LGA birth rate is about 10%. Recent literature continues to support the higher rates of obesity in LGA infants. However, there is a knowledge gap for their lifetime risk for adverse cardiometabolic outcomes. Potential factors that may modify the risk in early infancy include catch-down early postnatal growth, reduction in body fat growth trajectory, longer breastfeeding duration, and presence of a healthy gut microbiome. The early postnatal period may be a critical window of opportunity for active interventions to mitigate or prevent obesity and potential adverse metabolic consequences in later life. A variety of promising candidate biomarkers for the early identification of metabolic alterations in LGA infants is also discussed. IMPACT: LGA infants are the greatest risk category for future obesity, especially if they experience rapid postnatal growth during infancy. Potential risk modifying secondary prevention strategies in early infancy in LGA infants include catch-down early postnatal growth, reduction in body fat growth trajectory, longer breastfeeding duration, and presence of a healthy gut microbiome. LGA infants may be potential low-hanging fruit targets for early preventive interventions in the fight against childhood obesity.

Effectiveness of Dual Medication Therapy (Oral Acetaminophen and Oral Ibuprofen) for the Management of Patent Ductus Arteriosus in Extremely Premature Infants: A Feasibility Trial.

OBJECTIVE: The study aimed to evaluate the efficacy of dual medication therapy (DMT) with oral acetaminophen and oral ibuprofen for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA). STUDY DESIGN: In a prospective case-control cohort study (July 2017-May 2019), infants <29 weeks' gestational age and birth weight <1,000 g at ≤14 postnatal days with hsPDA and ratio of the smallest ductal diameter to the ostium of the left pulmonary artery diameter >0.5 were eligible. Infants received 10 mg/kg oral ibuprofen followed by two additional doses of 5 mg/kg at 24 and 48 hours after the initial ibuprofen dose and concomitant treatment with 15 mg/kg oral acetaminophen every 6 hours for 3 days (12 doses). Success of PDA treatment was defined as a small or absent PDA as ascertained by echocardiographic measurements. The p-values of comparisons were adjusted for multiple comparisons to preserve an error rate of 5%. RESULTS: Overall, 20 infants received oral DMT and 11 infants received intravenous single medication therapy (SMT) with ibuprofen. The rates of successful PDA treatment following the first treatment in DMT and SMT groups were not statistically different (11/20 [55%] vs. 4/11 [36%], p = 0.46). However, DMT significantly decreased PDA size (mean difference = 0.54 mm, 95% confidence interval [CI]: 0.21-0.96, adjusted p-value = 0.0002) and PDA/LPA ratio (mean difference = 0.27, 95% CI: 0.10-0.47, adjusted p-value = 0.0004). We observed no evidence of hematologic, hepatic, or renal impairment. CONCLUSION: DMT achieved a greater degree of PDA closure than SMT and did not result in abnormalities in hepatic and renal profile. KEY POINTS: · No consensus on optimal medication for PDA treatment is available.. · Dual oral medication therapy (ibuprofen and acetaminophen) could be an effective alternative treatment for PDA.. · Dual oral medication therapy (ibuprofen and acetaminophen) may have a better safety profile than currently approved medications such as intravenous indomethacin and intravenous ibuprofen..

Charge Nurses Taking Charge, Challenging the Culture of Culture-Negative Sepsis, and Preventing Central-Line Infections to Reduce NICU Antibiotic Usage.

OBJECTIVE: We aimed to reduce our monthly antibiotic usage rate (AUR, days of treatment per 1,000 patient-days) in the neonatal intensive care unit (NICU) from a baseline of 330 (July 2015-April 2016) to 200 by December 2018. STUDY DESIGN: We identified three key drivers as follows: (1) engaging NICU charge nurses, (2) challenging the culture of culture-negative sepsis, and (3) reducing central-line associated bloodstream infections (CLABSI). Our main outcome was AUR. The percentage of culture-negative sepsis that was treated with antibiotics for >48 hours and CLABSI was our process measure. We used hospital cost/duration of hospitalization and mortality as our balancing measures. RESULTS: After testing several plan-do-study-act (PDSA) cycles, we saw a modest reduction in AUR from 330 in the year 2016 to 297 in the year 2017. However, we did not find a special-cause variation in AUR via statistical process control (SPC) analysis (u'-chart). Thereafter, we focused our efforts to reduce CLABSI in January 2018. As a result, our mean AUR fell to 217 by December 2018. Our continued efforts resulted in a sustained reduction in AUR beyond the goal period. Importantly, cost of hospitalization and mortality did not increase during the improvement period. CONCLUSION: Our sequential quality improvement (QI) efforts led to a reduction in AUR. We implemented processes to establish a robust antibiotic stewardship program that included antibiotic time-outs led by NICU charge nurses and a focus on preventing CLABSI that were sustained beyond the QI period. KEY POINTS: · This is a quality improvement project to reduce antibiotic usage in NICU.. · Charge nurses should take charge to reduce infections in NICU.. · Central line infections should be reduced to decrease antibiotic usage..

Glucose Gel in Infants at Risk for Transitional Neonatal Hypoglycemia.

OBJECTIVE: To evaluate whether glucose gel as a supplement to feedings in infants admitted to the newborn nursery at risk for neonatal hypoglycemia (NH) reduces the frequency of transfer to a higher level of care for intravenous dextrose treatment. STUDY DESIGN: We revised our newborn nursery protocol for management of infants at risk for NH to include use of 40% glucose gel (200 mg/kg). Study population included late preterm, small and large for gestational age infants, and infants of diabetic mothers. We compared outcomes before (4/1/14-3/31/15: Year 1) and after (4/1/15-3/31/16: Year 2) initiation of the revised protocol. Our prospective primary outcome was transfer to the neonatal intensive care unit (NICU) for treatment with a continuous infusion of dextrose. RESULTS: NICU transfer for management of NH fell from 8.1% in Year 1 (34 of 421 at-risk infants screened) to 3.7% in Year 2 (14 of 383 at-risk infants screened). Rate of exclusive breastfeeding increased from 6% in Year 1 to 19% in Year 2. Hospital charges for the study population decreased from 801,276 USD to 387,688 USD in Year 1 and Year 2, respectively. CONCLUSION: Our study supports the adjunctive use of glucose gel to reduce NICU admissions and total hospitalization expense.

The association of overweight and obesity with spirometric values in minority children referred for asthma evaluation.

BACKGROUND: Overweight, obesity, and asthma are more prevalent in minority children; yet, the association of overweight and obesity with spirometric values in asthmatic minorities is not well characterized. OBJECTIVE: To study the relationship between weight, ethnicity, and spirometric values in children referred for asthma evaluation to a large inner-city hospital in Bronx, NY. METHODS: Retrospective review of spirometry done at the first pulmonary clinic visit of 980 asthmatic children, aged 7-20 years, was conducted. Linear regression analysis was performed to elucidate the association of overweight and obesity with pulmonary function among Whites, African Americans, and Hispanics compared with their normal weight counterparts. RESULTS: More African Americans (58%) and Hispanics (65.4%) were overweight and obese than Whites (51.2%) (p < .05). Compared with their normal weight counterparts, percent forced expiratory volume in the 1st second (FEV(1))/forced vital capacity (FVC) ratio was lower in both overweight and obese African Americans (2.99%, p < .05 and 3.56%, p < .01, respectively) and Hispanics (2.64%, p < .05 and 2.36%, p < .05, respectively); these differences were found in obese (3.73%, p < .05) but not in overweight (0.68%, p = .7) Whites. CONCLUSIONS: FEV(1)/FVC ratio was lower in both overweight and obese African American and Hispanic children, while this association was present only among obese Whites compared with their normal weight counterparts. These results suggest that spirometric measures of lower airway obstruction decrease with smaller weight increments in minority children when compared with White children. In the context of the higher prevalence of overweight and obesity among African Americans and Hispanics, our findings offer one potential explanation for increased asthma among minority children.

Longitudinal Trajectory and Early Life Determinant of Childhood Adipokines: Findings From a Racially Diverse Birth Cohort.

CONTEXT: Leptin and adiponectin play important roles in systemic metabolic homeostasis, beginning in utero. Limited data exist on the levels and trajectories of these 2 hormones at birth and in childhood and their biological and social determinants. OBJECTIVE: We examined the longitudinal trajectories of leptin and adiponectin from birth to early childhood, along with influential prenatal and infancy factors, and whether the trajectories and risk factors differ by preterm birth status. METHODS: We included mother-infant pairs in the Boston Birth Cohort, a predominantly Black, indigenous, and people of color (BIPOC) study population. We measured infant plasma leptin and adiponectin levels at birth and in early childhood. We examined longitudinal trajectories and the associated prenatal maternal and infancy factors. We analyzed 716 infants (158 preterm) who had leptin and adiponectin measured at birth and in early childhood (mean corrected age 2.18 years [interquartile range, 0.4-10.4]). RESULTS: Cord leptin was higher in term infants (40 230 vs 20 481 in preterm, P < 0.0001) but childhood leptin did not differ by prematurity (4123 in term vs 4181 in preterm, P = 0.92). Adiponectin was higher in term infants at birth (18 416 vs 11 223, P < 0.0001) and in childhood (12 108 vs 10532, P = 0.04). In stepwise regression, Black race was associated with higher childhood leptin and lower childhood adiponectin. Female sex was associated with higher childhood leptin levels and lower childhood adiponectin levels in multivariable regression models. CONCLUSION: Our results highlight preterm status, race, and biological sex as predictors of adipokine trajectory throughout childhood. These findings raise the possibility that early life programming of adipokines may contribute to higher metabolic risk in life, especially among Black children born preterm.

Frequency of Acute Kidney Injury and Association With Mortality Among Extremely Preterm Infants.

Importance: Neonatal acute kidney injury (AKI) is common and associated with morbidity and mortality. The temporal relationship between AKI and critical illness, as well as the frequency of AKI definition components (urine output and serum creatinine [sCr] concentration change), are unknown in extremely low-birth-weight (ELBW) (<1000 g), extremely preterm (<29 weeks' completed gestational age [GA]) infants. Objective: To measure the frequency of AKI from birth to death or discharge with attention to the definition components as well as the temporal relationship of AKI to critical illness and death. Design, Setting, and Participants: A single-center, multiyear, retrospective cohort study was conducted at an academic level IV neonatal intensive care unit between January 1, 2012, and January 1, 2020. Participants included inborn ELBW and infants at 22 to 28 weeks' completed GA with confirmed congenital anomalies who survived 12 hours or more. Exposures: Extremely preterm birth and ELBW. Main Outcomes and Measures: The primary outcome was AKI frequency. The timing, severity, and criteria for AKI were measured. The temporal relationship between AKI, organ dysfunction, and outcomes were quantified using odds ratios (ORs), logistic regression, and Shapley Additive Explanations. Acute kidney injury recognition, imaging, pediatric nephrology consultation, and follow-up were determined. Results: A total of 436 infants (52% male; 44% Black) met the inclusion criteria (median BW, 725 g; median GA, 25.7 wk). Acute kidney injury was common in the first week of life (44%), primarily based on the change in the sCr concentration criterion (88%), and negatively associated with GA (OR, 0.69; 95% CI, 0.60-0.78), but positively associated with antecedent critical illness (OR, 1.17; 95% CI, 1.12-1.23), severe intraventricular hemorrhage (OR, 1.86; 95% CI, 1.12-3.08), late-onset sepsis (OR, 1.03; 95% CI, 1.02-1.03), and mortality (OR, 2.77; 95% CI, 1.63-4.72). Acute kidney injury had negligible clinical contribution to death within the model (Shapley Additive Explanation, <0.5% change to outcome) relative to antecedent patient-concentration organ dysfunction (6%-15% change). Among infants with severe AKI, recognition (32%), nephrology inpatient consultation (16%), and outpatient follow-up (9%) were not common. Conclusions and Relevance: In this cohort study of ELBW infants, AKI was common in the first week of life, inversely associated with GA, and followed organ (primarily cardiovascular) dysfunction. Acute kidney injury considered as the primary pathway to mortality was rare, and amelioration of AKI to modify death was not well supported.

Dual medication therapy (acetaminophen and ibuprofen) for the management of patent ductus arteriosus in preterm infants: a systematic review and meta-analysis.

OBJECTIVE: To examine the efficacy of dual medication therapy (intervention) (DMT: acetaminophen and ibuprofen) vs. single medication therapy (control) (SMT: ibuprofen) for medical management of PDA (outcomes) in preterm infants (population). STUDY DESIGN: We systematically searched multiple sources to identify randomized controlled trials (RCT) and non-randomized studies (NRS) that compared DMT to SMT for management of hemodynamically significant PDA. RESULTS: We identified two RCTs and four NRS. There were no differences in the rates of successful PDA closure following the first treatment course between DMT and SMT (RR = 1.23 [95% CI 0.89-1.70] for NRS and RR = 1.18 [95% CI 0.66-2.10] for RCTs), nor were there significant differences in secondary outcomes and adverse events including PDA ligation, bronchopulmonary dysplasia, and necrotizing enterocolitis etc. Markers of hepatic/renal function did not change significantly during treatment. CONCLUSION: We found no evidence for superiority of DMT over SMT in PDA management.

Maternal and fetal factors affecting cord plasma leptin and adiponectin levels and their ratio in preterm and term newborns: New insight on fetal origins of metabolic dysfunction.

Background: Understanding of maternal and fetal factors affecting leptin, adiponectin, and adiponectin:leptin ratio at birth may provide valuable insights into potential future risk of metabolic alterations and inform primordial prevention and precision nutrition strategies. The objective of this study is to identify maternal and fetal risk factors that affect leptin and adiponectin levels (markers of adiposity) and adiponectin/leptin ratio (a marker of dysfunctional adipose tissue) at birth. Methods: We studied mother-infant pairs in the Boston Birth Cohort. Cord blood was collected at birth. We used student t- tests to compare log normalized cord leptin and adiponectin levels. Regression analysis was performed to examine the association of maternal and fetal factors with leptin and adiponectin levels and adiponectin:leptin ratio at birth in both term and preterm infants. Results: We analyzed 1012 infants (245 preterm). Both cord leptin and adiponectin were higher in term infants than preterm infants (10.2 ± 0.9 vs. 9.2 ± 1.3, P < 0.0001 and 9.5 ± 0.7 vs. 8.9 ± 0.8, P < 0.0001, respectively). Cord leptin was higher for Black infants (10.1 ± 1.1 vs. 9.9 ± 1.2; P < 0.001) although Black (ref: non-Black) infants had lower cord adiponectin levels (9.3 ± 0.8 vs. 9.5 ± 0.7; P = 0.01). Ratio of adiponectin to leptin (log normalized) was higher in preterm infants (-0.24) vs. term infants (-0.69). On regression analysis, cord leptin was positively associated with longer gestational age (GA), birth weight z score, Black race, maternal overweight and obesity, gestational diabetes and pregestational diabetes mellitus and negatively associated with male sex. Cord adiponectin was positively associated with GA, birth weight z score and negatively with Black race and male sex. Adiponectin:leptin ratio was positively with male sex and negatively with GA, birth weight z score, Black race, gestational DM, pregestational DM and maternal overweight and obesity. Conclusions: We identified several factors that affect leptin and adiponectin levels along with adiponectin-leptin ratio at birth beyond GA and birth weight which could also play an important role in influencing the trajectory of these hormones and future cardiometabolic outcomes. This knowledge can help tailor precision nutrition interventions.

Antenatal and neonatal factors contributing to extra uterine growth failure (EUGR) among preterm infants in Boston Birth Cohort (BBC).

OBJECTIVE: Identify antenatal and neonatal factors associated with primary outcome of EUGR. METHODS: 1063 preterm infants from a subset of the BBC were included in this prospective cohort study. Regression analysis was carried out to evaluate associations of EUGR with antenatal factors and neonatal factors. RESULTS: 6.1% of the infants had in-utero growth restriction (IUGR) at birth and 21.7% of infants had EUGR. The adjusted odds ratio for EUGR status were significant for birth weight (OR 0.99, p = 0.00, CI 0.99-0.99), for GA at birth (OR 4.58, p = 0.00, CI 3.25-6.44), for PDA (OR 2.9, p = 0.02, CI 1.17-7.1), for NEC (OR 5.14, p = 0.012, CI 1.44-18.3) and for day of life of reaching full feeds (OR 1.04, p = 0.001, CI 1.01-1.06). CONCLUSION: This study highlights important factors associated with EUGR. Additional studies are needed to gain further insight.

Effects of standardized feeding protocol on growth velocity and necrotizing enterocolitis in extremely low birth weight infants.

OBJECTIVE: To assess the effect of a standardized feeding protocol (SFP) on growth velocity (GV) and necrotizing enterocolitis (NEC) in extremely low birth weight infants. METHODS: This single-study center retrospectively compared growth, nutritional, and gastrointestinal outcomes in two infant cohorts before (cohort 1; n = 145) and after (cohort 2; n = 69) SFP implementation. RESULTS: Although weekly GV in the first 4 weeks of life did not differ between the two cohorts, median GV at 36 weeks' post-menstrual age (PMA) was higher in cohort 2 compared with cohort 1 (26.8 g/day [24.7, 28.9] vs 24.9 g/day [22.9, 28.3], p = 0.02). The odds of NEC were lower in cohort 2 by 63% after adjusting for birth weight, small-for-gestational-age, and gender (OR = 0.38, 95% CI 0.142-0.993, p = 0.047). CONCLUSION: Our SFP was associated with improved GV at 36 weeks' PMA and a lower adjusted rate of NEC.

Comparison of extubation success using noninvasive positive pressure ventilation (NIPPV) versus noninvasive neurally adjusted ventilatory assist (NI-NAVA).

OBJECTIVE: Compare rates of initial extubation success in preterm infants extubated to NIPPV or NI-NAVA. STUDY DESIGN: In this pilot study, we randomized 30 mechanically ventilated preterm infants at the time of initial elective extubation to NI-NAVA or NIPPV in a 1:1 assignment. Primary study outcome was initial extubation success. RESULTS: Rates of continuous extubation for 120 h were 92% in the NI-NAVA group and 69% in the NIPPV group (12/13 vs. 9/13, respectively, p = 0.14). Infants extubated to NI-NAVA remained extubated longer (median 18 vs. 4 days, p = 0.02) and experienced lower peak inspiratory pressures (PIP) than infants managed with NIPPV throughout the first 3 days after extubation. Survival analysis through 14 days post extubation showed a sustained difference in the primary study outcome until 12 days post extubation. CONCLUSIONS: Our study is the first to suggest that a strategy of extubating preterm infants to NI-NAVA may be more successful.

Cell phones: modern man's nemesis?

Over the past decade, the use of mobile phones has increased significantly. However, with every technological development comes some element of health concern, and cell phones are no exception. Recently, various studies have highlighted the negative effects of cell phone exposure on human health, and concerns about possible hazards related to cell phone exposure have been growing. This is a comprehensive, up-to-the-minute overview of the effects of cell phone exposure on human health. The types of cell phones and cell phone technologies currently used in the world are discussed in an attempt to improve the understanding of the technical aspects, including the effect of cell phone exposure on the cardiovascular system, sleep and cognitive function, as well as localized and general adverse effects, genotoxicity potential, neurohormonal secretion and tumour induction. The proposed mechanisms by which cell phones adversely affect various aspects of human health, and male fertility in particular, are explained, and the emerging molecular techniques and approaches for elucidating the effects of mobile phone radiation on cellular physiology using high-throughput screening techniques, such as metabolomics and microarrays, are discussed. A novel study is described, which is looking at changes in semen parameters, oxidative stress markers and sperm DNA damage in semen samples exposed in vitro to cell phone radiation.

Oxidative stress & male infertility.

The male factor is considered a major contributory factor to infertility. Apart from the conventional causes for male infertility such as varicocoele, cryptorchidism, infections, obstructive lesions, cystic fibrosis, trauma, and tumours, a new and important cause has been identified: oxidative stress. Oxidative stress is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body. It is a powerful mechanism that can lead to sperm damage, deformity and eventually, male infertility. This review discusses the physiological need for ROS and their role in normal sperm function. It also highlights the mechanism of production and the pathophysiology of ROS in relation to the male reproductive system and enumerate the benefits of incorporating antioxidants in clinical and experimental settings.

Altered hypoxia-inducible factor-1α (HIF-1α) signaling contributes to impaired angiogenesis in fetal lambs with persistent pulmonary hypertension of the newborn (PPHN).

Previous studies in adult pulmonary hypertension reported that increased hypoxia-inducible factor-1α (HIF-1α) signaling contributes to pulmonary vascular remodeling. However, alterations in endothelial HIF-1α signaling and its contribution to impaired angiogenesis in persistent pulmonary hypertension of the newborn (PPHN) remain unclear. We investigated the hypothesis that HIF-1α levels are increased in lung endothelial cells in PPHN and contribute to impaired angiogenesis function. We examined HIF-1α expression and promoter activity in the isolated pulmonary artery endothelial cells (PAEC) from fetal lambs with or without PPHN induced by prenatal ductus arteriosus constriction. We measured the levels of HIF-1α downstream targets, vascular endothelial growth factor (VEGF) and glycolytic protein, hexokinase 2 (Hek-2) in PAEC from PPHN, and control lambs. We examined the effect of small interfering-RNA (siRNA) mediated knockdown of native HIF-1α on VEGF expression and in vitro angiogenesis function of PPHN-PAEC. HIF-1α protein levels were higher in the isolated PAEC from PPHN-lambs compared to controls. HIF-1α promoter activity and Hek-2 protein levels were higher in PPHN. VEGF protein levels and in vitro angiogenesis function were decreased in PAEC from PPHN lambs. HIF-1α silencing significantly increased the expression of VEGF and improved the angiogenesis function of PPHN PAEC. Aberrant HIF-1α signaling contributes to endothelial dysfunction and decreased angiogenesis in PPHN.

Successful implementation of an intracranial hemorrhage (ICH) bundle in reducing severe ICH: a quality improvement project.

OBJECTIVE: Our specific, measurable, attainable, relevant, and time-limited (SMART) aim was to reduce the incidence of severe intracranial hemorrhage (ICH) among preterm infants born <30 weeks' gestation from a baseline of 24% (January 2012-December 2013) to a long-term average of 11% by December 2015. STUDY DESIGN: We instituted an ICH bundle consisting of elements of the "golden hour" (delayed cord clamping, optimized cardiopulmonary resuscitation, improved thermoregulation) and provision of cluster care in the neonatal intensive care unit (NICU). We identified key drivers to achieve our SMART aims, and implemented quality improvement (QI) cycles: initiation of the ICH bundle, education of NICU staff, and emphasis on sustained adherence. We excluded infants born outside our facility and those with congenital anomalies. RESULTS: Using statistical process control analysis (p-chart), the ICH bundle was associated with successful reduction in severe ICH (grade 3-4) in our NICU from a prebundle rate of 24% (January 2012-December 2013) to a sustained reduction over the next 4 years to an average rate of 9.7% by December 2017. Results during 2016-2017 showed a sustained improvement beyond the goal for 2014-2015. Over the same interval, there was improvement in admission temperatures [median 36.1 °C (interquartile range: 35.3-36.7 °C) vs. 37.1 °C (36.8-37.5 °C), p < 0.01] and a decrease in mortality rate [pre: 16/117 (14%) vs. post: 16/281 (6%), P < 0.01]. CONCLUSION: Our multidisciplinary QI initiative decreased severe ICH in our institution from a baseline rate of 24% to a lower rate of 9.7% over the ensuing 4 years. Intensive focus on sustained implementation of an ICH bundle protocol consisting of improved delivery room management, thermoregulation, and clustered care in the NICU was temporally associated with a clinically significant reduction in severe ICH.

Magnetic activated cell sorting (MACS): utility in assisted reproduction.

Assisted reproductive techniques (ART) have now been extensively incorporated in the management of infertile couples. But even after rapid methodological and technological advances the success rates of these procedures have been below expectations. This has led to development of many sperm preparation protocols to obtain an ideal semen sample for artificial reproduction. Sperm apoptosis has been heavily linked to failures in reproductive techniques. One of the earliest changes shown by apoptotic spermatozoa is externalization of phosphatidyl serine. Magnetic activated cell sorting (MACS) is a novel sperm preparation technique that separates apoptotic and non-apoptotic spermatozoa based on the expression of phosphatidylserine. This has led to the incorporation of MACS as a sperm preparation technique. The review highlights the principle and mechanism of this novel technique and enumerates its advantages as a sperm preparation technique. Its utility in ART as an efficient tool for sperm recovery and its application in cryopreservation of semen samples is also explained.