Milrinone Versus Sildenafil in Treatment of Neonatal Persistent Pulmonary Hypertension: A Randomized Control Trial.

ABSTRACT: Persistent pulmonary hypertension of the newborn (PPHN) is a condition caused by failure of pulmonary vascular adaptation at birth, resulting in severe hypoxia. Several therapeutic modalities are being tried in developing countries where established therapies (inhaled nitric oxide and extracorporeal membrane oxygenation) are widely unavailable. This study aimed to assess the efficacy of milrinone versus sildenafil as available alternative therapeutics in treating PPHN. Forty neonates (>34 weeks) admitted to neonatal intensive care units with evidence of PPHN were randomly allocated to receive either oral sildenafil (0.5-2 mg/kg/6 hours) or intravenous milrinone (0.25-0.75 mic/kg/min). Primary outcomes included improvements in systolic pulmonary artery pressure and oxygen saturation index (OSI) at 24 and 48 hours after treatment. Secondary outcomes included the duration of hospitalization and mechanical ventilation. The ClinicalTrials identifier is NCT04391478. Both groups showed significant improvement in the post-treatment hemodynamic variables compared with pretreatment levels ( P < 0.05 for all parameters). Systolic pulmonary artery pressure and OSI values significantly improved in both study groups compared with baseline ( P < 0.001). The 24-hour and 48-hour post-treatment OSI values were much lower in the milrinone group than those in the sildenafil group ( P < 0.05). The length of hospital stay was significantly shorter in the milrinone group than that in the sildenafil group ( P < 0.05). There were no significant differences in the duration of mechanical ventilation, incidence of intracranial hemorrhage and pulmonary hemorrhage, or mortality between the 2 groups ( P > 0.05). In conclusion, milrinone and sildenafil are effective and well-tolerated in neonates with PPHN, particularly when inhaled nitric oxide and extracorporeal membrane oxygenation are not available. Milrinone is superior to sildenafil in improving oxygenation without lowering blood pressure parameters.

Gut priming with bovine colostrum and T regulatory cells in preterm neonates: a randomized controlled trial.

BACKGROUND: Necrotizing enterocolitis (NEC) and neonatal sepsis are still considered major problems, especially in formula-fed preterm neonates. This study aimed to investigate the effect of bovine colostrum on T regulatory cells, NEC, and late-onset sepsis in preterm neonates ≤34 weeks. METHODS: This prospective double-blind randomized controlled trial was conducted on 80 preterm infants who were randomly assigned to either the bovine colostrum group (n = 32) or control group (n = 48). T lymphocytes and their subsets, necrotizing enterocolitis, late-onset sepsis (LOS) and its severity, feeding tolerance, growth, length of hospital stay, and mortality were documented. RESULTS: The bovine colostrum group showed higher follow-up levels of CD4+CD25+ FOXP3+ T lymphocyte % (FOXP3 Tregs). FOXP3 Tregs and its difference in change levels between baseline and follow-up were considered as the most related factors to the bovine colostrum. Bovine colostrum group showed positive trends for reduction of sepsis severity and mortality with no significant difference in the incidence of NEC, LOS, and length of hospital stay. CONCLUSIONS: Preterm neonates who received bovine colostrum showed a higher FOXP3 Treg level. IMPACT: Bovine colostrum has no significant effect on the incidence of necrotizing enterocolitis. FOXP3 T regulatory cells and their increased level between baseline and follow-up is considered as the most influencing factors related to the bovine colostrum. Positive trends were noted for reduction of sepsis severity and concomitant mortality, but the study lacked the power to assess these outcomes.

Effect of right lateral position with head elevation on tracheal aspirate pepsin in ventilated preterm neonates: randomized controlled trial.

Objective: To evaluate the effect of right lateral positioning in comparison with supine positioning on tracheal aspirate pepsin levels as a marker of aspiration of gastric contents in ventilated preterm neonates. Study design: This randomized controlled trial was conducted on 60 ventilated preterm neonates <35 weeks; 30 neonates were nursed in right lateral position for 6 hours while the other 30 neonates were nursed in supine position for 6 hours. Tracheal aspirate sample was obtained from each neonate in both the groups just after the end of 6 hours and pepsin level was measured. Results: Neonates in right lateral position group had significantly lower tracheal pepsin level than neonates in supine position group (6 ng/ml) interquartile range [IQR] (3-20) versus 15 ng/ml [IQR] (5.5-90) (p = .024). There is positive correlation between tracheal aspirate pepsin level and fraction of inspired oxygen (FiO2) needed during the intervention (r = 0.383, p = .040). There is no correlation between tracheal pepsin level and gestational age, birth weight, or duration of mechanical ventilation and other ventilatory settings. Conclusion: Nursing ventilated premature infants in right lateral position is associated with decreased aspiration of gastric contents.

Early Zinc Supplementation and Enhanced Growth of the Low-Birth Weight Neonate.

BACKGROUND: Nutritional deficits are almost universal in Low-Birth Weight babies. Zinc is essential for normal infant growth and its supplementation assists growth probably through insulin-like growth factor-1. AIM: This double-blind randomized-controlled trial aimed at evaluating the role of zinc in catch-up growth of low-birth-weight infants and investigating its proposed mediator. MATERIAL AND METHODS: The study was conducted in Ain Shams University Maternity Hospital. Two hundred low-birth-weight neonates were simply randomized to either oral zinc therapy or placebo. Anthropometric measurements were recorded at birth, 3, 6, and 12 months; including weight, recumbent length, head, waist, chest, and mid-upper arm circumferences, and triceps and sub-scapular skin fold thickness. RESULTS: We found that initial and 3-months measurements, except weight, were comparable in the 2 groups. All measurements at 6- and 12-months, except sub-scapular skin-fold-thickness, were significantly higher in zinc group than placebo. Catch-up growth, at 12-months, was significant in zinc group and was significantly higher in appropriate-for-gestational-age vs. small-for-gestational-age, in preterm vs. term, and in male vs. female infants. The median 6-months insulin-like growth factor-1 levels were significantly higher in zinc group. CONCLUSION: We conclude that early start of oral zinc supplementation in low-birth-weight neonates assists catch-up growth, probably through rise of insulin-like growth factor-1.

Surveillance of health care-associated infections in a tertiary hospital neonatal intensive care unit in Egypt: 1-year follow-up.

BACKGROUND: Reported rates of neonatal health care-associated infections (HAIs) in neonatal intensive care units (NICUs) have risen rapidly in recent years. Little data are available in Egypt, however. The aim of the present study was to determine the incidence of and risk factors for HAIs in the NICU of Ain Shams University Hospital of Obstetrics and Gynecology. METHODS: A prospective study was carried out on all neonates admitted in the NICU of Ain Shams University Hospital of Obstetrics and Gynecology in 2012. Centers for Disease Control and Prevention criteria were followed for identifying HAIs. RESULTS: A total of 434 neonates were enrolled in the study. The cumulative incidence of HAIs in the NICU was 28%. Bloodstream infections accounted for 85% of HAI episodes; pneumonia, for 10%. The most common organism isolated was Klebsiella spp. The main risk factors identified on multivariable analysis were gestational age <38 weeks (relative risk [RR], 1.63), birth weight <1,500 g (RR, 1.39), mechanical ventilation (RR, 1.74), and surgical procedures (RR, 1.65). The mortality rate attributed to HAIs was 11.75%, and the extra hospital length of stay attributed to HAIs was 8 days. CONCLUSION: The high incidence of HAI identified in the study NICU mandates more vigorous infection control interventions.

Single dose recombinant erythropoietin versus moderate hypothermia for neonatal hypoxic ischemic encephalopathy in low resource settings.

OBJECTIVE: To determine the safety and efficacy of single dose systemic recombinant human erythropoietin (rEPO) in neonates with perinatal hypoxic Ischemic Encephalopathy (HIE), and its effect on serum brain-derived neurotrophic factor (BDNF) and neuron-specific enolase (NSE). METHODS: Forty-five full-term neonates; 30 with perinatal HIE and 15 controls were studied. HIE neonates were randomized into three intervention groups (first 6 h of life): 10 received single subcutaneous 1500 U/kg rEPO at day-1, 10 subjected to hypothermia for 72 h and 10 received supportive care. BDNF and NSE measured during first 6 h and day 5 postnatal. Daily Thompson's score, MRI brain and neuromuscular function scale for survivors at 3 months of age were done. RESULTS: Hypothermia group had best survival especially with stage-II Sarnat scale, followed by rEpo and supportive group. BDNF day-5 was significantly higher in each group compared to controls. MRI score and neuromuscular function score were non-significantly lower in the hypothermia group compared to rEPO. CONCLUSIONS: Therapeutic hypothermia was superior to single dose rEpo for neuro-protection in HIE especially in patients with stage-II Sarnat scale. Therapeutic effect of combined rEPO multiple dosing and modest hypothermia therapy should be studied.

Targeted versus Universal Neonatal Hearing Screening in a Single Egyptian Center.

Aim. To compare targeted neonatal hearing screening (TNHS) and universal neonatal hearing screening (UNHS) since many developing countries, including Egypt, implement selective screening for high-risk neonates. Methods. 150 neonates were assessed; 50 full terms consecutively admitted to the well-baby nursery and 100 neonates consecutively admitted to neonatal intensive care unit (NICU), Ain Shams University. Patients were further subdivided into high-risk group which included 50 neonates with multiple risk factors for hearing loss and low risk group which included 50 neonates with only one risk factor. Transient evoked otoacoustic emissions (TEOAEs) were used for hearing screening. Auditory brain response (ABR) was performed 3 months later for failed TEOAEs. Results. The most frequent risk factor was consanguinity (46%). In the well-baby population, 16% failed TEOAEs. In the NICU, 30% of the low risk and 38% of the high risk groups failed TEOAEs. Regarding ABR, failed results were 12%, 10%, and 8% in the high-risk, low-risk, and healthy groups, respectively. Conclusion. The use of TNHS would have missed 8% of neonates from the well-baby group who actually had PCHL (permanent congenital hearing loss). The use of UNHS would identify all cases with PCHL, allowing for early intervention and follow-up.

Serum OX40 ligand levels in asthmatic children: a potential biomarker of severity and persistence.

The costimulatory molecule OX40 and its ligand, OX40L, mediate key aspects of allergic airway inflammation in animal models of asthma, including eosinophilic airway inflammation, airway hyperresponsiveness, and T-helper type 2 (Th2) polarization. However, involvement of these molecules in Th2-dominated allergen-induced childhood asthma remains unclear. Therefore, we sought to examine OX40L expression in pediatric asthma across disease activity and attack severity. Serum OX40L concentrations were measured by ELISA in 50 children with atopic asthma (during and in between acute attacks), and in 40 healthy children serving as controls. The median and mean (SD) serum OX40L levels (1487 and 1560 [543] pg/mL) were significantly higher in asthmatic children during acute attacks in comparison with children in between attacks (731 and 689 [321] pg/mL) and in comparison with controls (193 and 157 [60.3] pg/mL). OX40L values were higher among children who presented with acute severe asthma exacerbations than in children with mild or moderate asthma exacerbations. During stability, patients with severe persistent asthma had significantly higher levels when compared with patients with moderate or mild persistent asthma. A positive correlation could be elicited between OX40L levels during exacerbations and the corresponding values during remission. Serum OX40L levels correlated negatively with peak expiratory flow rate and positively with absolute eosinophil count. Up-regulation of OX40L may play a critical role in development of childhood atopic asthma and is in favor of asthma severity. OX40L may represent a useful biomarker of monitoring allergic inflammation. OX40L is one of the most promising targets of immune intervention for treatment of these diseases.

Umbilical cord ghrelin in term and preterm newborns and its relation to metabolic hormones and anthropometric measurements.

The aim of the study was to assess umbilical cord ghrelin level in term and preterm newborns and its relation to other metabolic hormones and anthropometric measurements. A cross sectional comparative study included 50 normal appropriate-for-gestational-age newborns (25 full-terms; 25 preterm). Assessment of anthropometric measurements, cord levels of ghrelin, leptin, insulin and glucose were done to all newborns. Umbilical cord ghrelin was detected in all newborns. There was no significant difference between term and preterm groups regarding ghrelin, insulin and glucose. Leptin was significantly lower in preterm than term group. Sex and mode of delivery had no effects regarding all studied variables. There was no overall correlation between ghrelin and gestational age, anthropometric measurements, leptin, insulin or glucose in all newborns. Preterm group demonstrated significant correlations between ghrelin and weight, body mass index and abdominal circumference. An overall significant correlation was found between leptin and gestational age and anthropometric measurements in all newborns. In preterm group leptin correlated with weight, length, subscapular skin-fold thickness and abdominal circumference. To conclude the umbilical cord ghrelin was relatively invariable at birth between 30 and 41 weeks gestation showing no gestational age-related variation, unlike leptin, which was lower in preterm group indicating increased adipose mass and placental maturation with increased gestational age.

Evaluation of renal glomerular and tubular functional and structural integrity in neonates.

BACKGROUND: Renal cells are not fully differentiated at birth, representing a major risk in preterm infants. We evaluated glomerular and tubular functional integrity as well as structural integrity of renal tubules among healthy full-term and preterm infants as well as diseased preterm infants. METHODS: A total of 50 newborns (10 healthy full-term, 10 healthy preterm, and 30 diseased preterm, at 38.9 +/- 1.10, 34.2 +/- 0.92, and 32 +/- 2.47 weeks gestational age, respectively) were included in the present study. Glomerular function was assessed by measuring urinary levels of both microalbumin and immunoglobulin G as well as serum creatinine levels, whereas the proximal tubular function was investigated by measuring the urinary levels of both alpha1-microglobulin and beta2-microglobulin as well as retinol-binding protein. Also, distal tubular reabsorption capacity was investigated by assessing fractional excretion of sodium. Moreover, the structural integrity of renal proximal tubules was studied by measuring the urinary activities of both the brush-border membrane enzyme leucine-aminopeptidase (LAP) and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase. The preceding investigations were done on both the first and third days of life of all 50 newborns. RESULTS: Glomerular and tubular function and structure was relatively impaired at birth among both healthy and diseased preterm as well as healthy full-term neonates and improved rapidly thereafter. The diseased preterm neonates showed worse renal function and structure with minimal improvement regardless of the underlying sickness. CONCLUSION: Renal insufficiency and renal immaturity could be evaluated using enzymuria and low- and high-molecular-weight proteinuria as noninvasive methods.