Nehad Nasef

Patent ductus arteriosus in preterm infants: do we have the right answers?

Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants. Preterm newborns with PDA are at greater risk for several morbidities, including higher rates of bronchopulmonary dysplasia (BPD), decreased perfusion of vital organs, and mortality. Therefore, cyclooxygenase (COX) inhibitors and surgical interventions for ligation of PDA are widely used. However, these interventions were reported to be associated with side effects. In the absence of clear restricted rules for application of these interventions, different strategies are adopted by neonatologists. Three different approaches have been investigated including prophylactic treatment shortly after birth irrespective of the state of PDA, presymptomatic treatment using echocardiography at variable postnatal ages to select infants for treatment prior to the duct becoming clinically significant, and symptomatic treatment once PDA becomes clinically apparent or hemodynamically significant. Future appropriately designed randomized controlled trials (RCTs) to refine selection of patients for medical and surgical treatments should be conducted. Waiting for new evidence, it seems wise to employ available clinical and echocardiographic parameters of a hemodynamically significant (HS) PDA to select patients who are candidates for medical treatment. Surgical ligation of PDA could be used as a back-up tool for those patients who failed medical treatment and continued to have hemodynamic compromise.

Pentoxifylline therapy for late-onset sepsis in preterm infants: a randomized controlled trial.

Background: The role of pentoxifylline (PTX) in reducing mortality associated with neonatal sepsis is not well established. We aimed to assess the efficacy and safety of PTX as an adjunct to antibiotics on mortality and morbidity in preterm infants with late-onset sepsis (LOS). Methods: Double blind, randomized controlled trial was conducted on 120 preterm infants with LOS. They were randomly assigned to receive either intravenous PTX 5 mg/kg/hr for 6 hours on 6 successive days or placebo. Death before hospital discharge was our primary outcome and secondary outcomes were length of hospital stay, duration of respiratory support, duration of antibiotics use, short-term morbidity of preterm infants, tumor necrosis factor-alpha concentrations, C-reactive protein concentrations, and adverse effects of PTX. Results: A total of 120 infants were enrolled, 60 in each group, 78 (65%) infants had confirmed and 42 (35%) had suspected LOS. There were no significant differences between groups regarding mortality [6 (10%) in PTX vs. 10 (16.5%) in placebo, P = 0.44], short-term morbidity and combined mortality and/or short-term morbidity [18 (30%) vs. 24 (40%), P = 0.23]. PTX therapy was associated with significant reduction of serum tumor necrosis factor-alpha and C-reactive protein concentrations. The length of hospital stay, durations of respiratory support and antibiotic therapy were significantly shorter in the PTX group. Patients in PTX group had less need for vasopressors, lower incidence of metabolic acidosis, disseminated intravascular coagulopathy and thrombocytopenia. No adverse effects to PTX were reported. Conclusions: PTX has a beneficial adjuvant effect to antibiotic therapy in preterm infants with LOS without significant impact on neonatal mortality and morbidity.

Caffeine therapy in preterm infants

Caffeine is the most commonly used medication for treatment of apnea of prematurity. Its effect has been well established in reducing the frequency of apnea, intermittent hypoxemia, and extubation failure in mechanically ventilated preterm infants. Evidence for additional short-term benefits on reducing the incidence of bronchopulmonary dysplasia and patent ductus arteriosus has also been suggested. Controversies exist among various neonatal intensive care units in terms of drug efficacy compared to other methylxanthines, dosage regimen, time of initiation, duration of therapy, drug safety and value of therapeutic drug monitoring. In the current review, we will summarize the available evidence for the best practice in using caffeine therapy in preterm infants.

High‐flow nasal cannulae are associated with increased diaphragm activation compared with nasal continuous positive airway pressure in preterm infants

High‐flow nasal cannulae (HFNC) are increasingly used for respiratory management of preterm infants. However, their ability to provide support compared to nasal continuous positive airway pressure (CPAP) has been questioned. We compared the effect of HFNC versus nasal CPAP on diaphragm electrical activity (EAdi) in preterm infants.

Conventional Versus Prolonged Infusion of Meropenem in Neonates with Gram Negative Late Onset Sepsis: A Randomized Controlled Trial.

Background: Gram-negative bacteria are associated with significant morbidity and mortality in preterm and term newborns. Meropenem has widespread efficacy and often allows for monotherapy in this group. Prolonged infusion instead of infusion over 30 minutes has been suggested to result in higher microbiologic efficacy. Objective: To compare the clinical and microbiologic efficacy and safety of prolonged infusions versus conventional dosing of meropenem in neonates with Gram-negative late-onset sepsis (GN-LOS). Methods: A prospective, randomized clinical trial was conducted in neonates with GN-LOS admitted to neonatal intensive care unit (NICU), Mansoura University Children’s Hospital, between August 2013 and June 2015. Patients were randomly assigned to receive either intravenous infusion of meropenem over 4 hours (infusion group) or 30 minutes (conventional group) at a dosing regimen of 20 mg/kg/dose every 8 hours and 40 mg/kg/dose every 8 hours in meningitis and Pseudomonas infection. Clinical and microbiologic success in eradication of infection were the primary outcomes. Neonatal mortality, meropenem-related (MR) duration of mechanical ventilation, MR length of NICU stay, total length of NICU stay, duration of respiratory support (RS), duration of mechanical ventilation, MR duration of inotropes and adverse effects were secondary outcomes. Results: A total of 102 infants (51 in each group) were recruited. The infusion group demonstrated a significantly higher rate of clinical improvement and microbiologic eradication 7 days after starting meropenem therapy compared with the conventional group. Mortality and duration of RS were significantly less in the infusion group compared with conventional group. Acute kidney injury after meropenem treatment was significantly less in the infusion group compared with the conventional group. Conclusions: Prolonged infusion of meropenem in neonates with GN-LOS is associated with higher clinical improvement, microbiologic eradication, less neonatal mortality, shorter duration of RS and less acute kidney injury compared with the conventional strategy.

Role of ascorbate in lung cellular toxicity mediated by light-exposed parenteral nutrition solution.

Abstract Neonatal lung injury has been induced experimentally by infusion of multivitamin-containing light-exposed parenteral nutrition (PN) solutions. The objective was to explore the role of ascorbate in toxic effects of light-exposed PN on primary cultured foetal rat lung epithelial cells. Hydroperoxides were measured in 3% amino acid solutions at baseline, immediately after addition of either multivitamins or ascorbate alone (400 μg/mL) and again after a 24-h period of exposure to (or protection from) ambient light. Cellular toxicity was assessed by [C14]adenine release. Multivitamins or ascorbate alone increased hydroperoxides in PN, which was attenuated by light protection. Light-exposed PN containing multivitamins was more toxic to cells than baseline or light-protected PN. Exposure to ascorbate at concentrations both lower (< 5 μg/mL) and higher (> 1000 μg/mL) than normally contained in PN-induced oxidant-mediated cell death, as indicated by protective effects of hydroperoxide and hydroxyl radical scavengers. This study concludes that ascorbate generates toxic amounts of peroxide in PN solutions. The types and physiological importance of hydroperoxides induced by pro-oxidant effects of ascorbate require further evaluation in vivo.

Acute flaccid paralysis in a patient with sacral dimple.

Sacral dimples are the most common cutaneous anomaly detected during neonatal spinal examination. Congenital dermal sinus tract, a rare type of spinal dysraphism, occurs along the midline neuraxis from occiput down to the sacral region. It is often diagnosed in the presence of a sacral dimple together with skin signs, local infection, meningitis, abscess, or abnormal neurological examination. We report a case of acute flaccid paralysis with sensory level in a 4 mo old female infant with sacral dimple, diagnosed by magnetic resonance imaging to be a paraspinal subdural abscess. Surgical exploration revealed a congenital dermal sinus tract extending from the subdural abscess down to the sacral dimple and open to the exterior with a minute opening.

A newborn with facial hemangioma and sternal defect

Large facial segmental hemangiomas tend to be associated with extracutaneous abnormalities. We report a case of large progressive segmental facial hemangioma, sternal cleft and talipes equinovarus deformity.