Javeed Travadi

Pentoxifylline Reduces the Incidence and Severity of Necrotizing Enterocolitis in a Neonatal Rat Model

Necrotizing enterocolitis (NEC) is a potentially fatal illness in premature neonates. Tumor necrosis factor alpha (TNF-α) has been shown to play a central role in the inflammatory cascade leading to the development of NEC. Published evidence points to a significant role of pentoxifylline in inhibition of TNF-α and in reducing mucosal injury and improving healing in ischemia-reperfusion experiments. Our aim was to investigate the effect of pentoxifylline on the incidence of NEC in a neonatal rat model. Newborn Sprague-Dawley rat pups originating from eight separate litters were delivered by cesarean section at 21.5 d and were formula fed from birth by orogastric gavage. The rat pups were randomized to receive either intraperitoneal pentoxifylline (15 mg/kg/dose) or placebo, given every 8 h beginning at 24 h of age, in a blinded fashion. Experimental NEC was induced by exposure to hypoxia for 60 s followed by cold stress at 4°C for 10 min. The animals were euthanized at development of NEC or at 96 h and intestinal tissue was processed and examined for histologic changes of NEC. The incidence of NEC was significantly lower in the pentoxifylline group [pentoxifylline 5/38 versus placebo 15/36; p = 0.008, odds ratio (OR) = 0.21 95% confidence interval (CI) 0.07–0.67]. Among the pups developing NEC, significantly fewer rat pups treated with pentoxifylline had severe (≥3) intestinal injury scores [pentoxifylline 1/5 versus placebo 10/15; p = 0.031, OR 0.06, 95% CI 0.01–0.79]. We conclude that intraperitoneal administration of pentoxifylline significantly reduced the incidence and severity of NEC in our experimental animal model.

Targeted Oxygen in the Resuscitation of Preterm Infants, a Randomized Clinical Trial

BACKGROUND AND OBJECTIVES: Lower concentrations of oxygen (O2) (≤30%) are recommended for preterm resuscitation to avoid oxidative injury and cerebral ischemia. Effects on long-term outcomes are uncertain. We aimed to determine the effects of using room air (RA) or 100% O2 on the combined risk of death and disability at 2 years in infants <32 weeks’ gestation. METHODS: A randomized, unmasked study designed to determine major disability and death at 2 years in infants <32 weeks’ gestation after delivery room resuscitation was initiated with either RA or 100% O2 and which were adjusted to target pulse oximetry of 65% to 95% at 5 minutes and 85% to 95% until NICU admission. RESULTS: Of 6291 eligible patients, 292 were recruited and 287 (mean gestation: 28.9 weeks) were included in the analysis (RA: n = 144; 100% O2: n = 143). Recruitment ceased in June 2014, per the recommendations of the Data and Safety Monitoring Committee owing to loss of equipoise for the use of 100% O2. In non-prespecified analyses, infants <28 weeks who received RA resuscitation had higher hospital mortality (RA: 10 of 46 [22%]; than those given 100% O2: 3 of 54 [6%]; risk ratio: 3.9 [95% confidence interval: 1.1–13.4]; P = .01). Respiratory failure was the most common cause of death (n = 13). CONCLUSIONS: Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks’ gestation. This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably. Additional data are needed.

Staphylococcal scalded skin syndrome in an extremely premature neonate: a case report with a brief review of literature.

Abstract:  Staphylococcus aureus can cause a spectrum of exfoliative skin conditions including staphylococcal scalded skin syndrome (SSSS) which can present as a severe and life threatening illness in extremely premature neonates. We describe a case of an extremely premature neonate with SSSS and discuss relevant pathology and issues in clinical management.

Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants

BACKGROUND Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n‐3 long‐chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. METHODS We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen‐saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. RESULTS A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06). CONCLUSIONS Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.)

Patent ductus arteriosus in extremely preterm infants receiving phototherapy: Does shielding the chest make a difference? A randomized, controlled trial

Background: Patent ductus arteriosus (PDA), a common complication in extremely preterm infants, is associated with increased mortality and morbidity. Phototherapy has been associated with PDA, and one randomized, control trial has shown that shielding of the chest may decrease the risk of PDA. Aim: To examine if chest shielding reduces the incidence and severity of PDA in extremely preterm infants. Study design: Randomized clinical trial of infants < 29 wk gestation (stratified into two groups: <27 wk gestation and 27–28 wk gestation). Methods: Following written parental consent, eligible infants were randomized to receive phototherapy, with or without a chest shield. Ductal parameters were assessed by Doppler echocardiogram in all infants prior to starting phototherapy and at 48 h after initiation, or earlier if phototherapy was discontinued. Results: 54 infants were enrolled in the study. The incidence of PDA (shield 19/27 vs no shield 21/27), ductal size (1.4 vs 1.0 mm) and left atrial/aortic root (LA/Ao) ratio (1.2 vs 1.3) were similar in the two groups pre‐phototherapy. There was no difference between the groups post‐phototherapy in incidence (shield 12/27 vs no shield 13/27), ductal size (1.4 vs 1.5 mm) or LA/Ao ratio (1.1 vs 1.3).

Patent Ductus Arteriosus in Infants <29 Weeks Gestation - Outcomes and Factors Affecting Closure

ObjectiveTo determine Patent ductus arteriosus (PDA) closure rates for extremely preterm infants in a tertiary care centre, factors affecting response to indomethacin and outcomes of these infants relative to their PDA status.SettingNeonatal intensive care unit in tertiary-care children’s hospital.DesignRetrospective medical record review.MethodsA retrospective chart review of all infants <29 weeks gestation between 1st Jan 2003 and 30th June 2006 was carried out. Multiple courses of standard intravenous indomethacin (dose: 0.2 mg/kg 12 hourly; 3 doses) followed by a tail course (0.1 mg/kg/day; 3 doses) were used to treat PDA depending on clinical and hemodynamic status. Data on demographic characteristics, PDA status, use of indomethacin, and outcome factors such as chronic lung disease and mortality were collected.ResultsA total of 166 infants were identified in the study period, of which 15 were excluded. The median gestation was 27 weeks [IQR (25, 28)] and the mean (SD) birthweight was 950 (244) grams. The remaining infants (n=151) were divided into three groups. Group1 (n=47): no or non-significant PDA, Group 2 (n=91): significant PDA closed after indomethacin treatment (≥ 1 course) and Group 3 (n=13): significant PDA not responding to indomethacin. The closure rate of PDA with indomethacin treatment (group 2) was 87%. A low gestational age < 26 weeks (OR 5.6, 95% CI 1.6–19.9) and female sex (OR 5.8, 95% CI 1.5–22.8) was associated with poor response to indomethacin in our study population.ConclusionsMultiple indomethacin courses using the standard dosing approach result in high PDA closure rates for infants < 29 weeks gestation.

Gastrointestinal contrast studies in high-risk neonates with suspected necrotising enterocolitis - a note of caution

Abstract Upper gastrointestinal contrast studies are frequently performed in neonates to rule out conditions such as malrotation. Low osmolality water-soluble (LOWS) contrast media are currently considered safe for use in neonates. The clinical course of a neonate with suspected necrotising enterocolitis, who deteriorated significantly due to peritonitis following contrast study with LOWS, is reported. The possibility that LOWS contrast media may not always be safe in high-risk neonates is raised.

241 Patent Ductus Arteriosus |[ndash]| Is Surgical Ligation Necessary|[quest]| The Western Australian Experience

Patent ductus arteriosus (PDA) with a significant left-right shunt is associated with chronic lung disease (CLD), intraventricular haemorrhage (IVH) and necrotising enterocolitis (NEC). Surgical ligation is reserved for PDA refractory to medical treatment, however there is no clear evidence that this improves outcome. WCHS is the only tertiary perinatal/paediatric centre in Western Australia. Geographical isolation from the nearest cardiac surgical centre (3,500kms) has meant that ductal ligation has not been an option until recently. A retrospective data analysis was undertaken to test the hypothesis that outcomes of infants with persistent PDA were no worse than that of those with a closed duct. Patients and Methods: Infants born 1.4 or a ductal diameter of > 1.5 mm with a left-to-right shunt. Continuous data is summarised as median (IQR) and analysed with Mann-Whitney and Kruskal-Wallis tests. Duration of ventilation, oxygen and hospital stay were estimated using Kaplan-meier probability estimates and analysed using Cox proportional hazards regression model Results Total 284 infants <28 weeks gestation were included and 32 excluded. Twenty-four (10%) infants died at median (IQR) 15.5 (9–35) days. Relative to Group 1, the infants in Group 3 were at increased risk of death (adjusted OR = 4.01 (95% CI 1.12–14.51) p= 0.033). Deaths: Group1= 6/154; Group2= 7/65; Group3: deaths= 11/33. There was no significant difference between groups in the incidence of CLD, CLD or death, NEC, IVH, duration of oxygen or hospital stay but duration of ventilation tended to be longer in Group 3 (adjusted HR 0.66 (95% CI 0.41–1.06) p=0.082.

What does the world think of ankyloglossia

The diagnosis of tongue‐tie (or ankyloglossia) has increased more than 10‐fold in some countries. Whether this is a global phenomenon or related to cultural and professional differences is uncertain.

Cost is an important factor influencing active management of extremely preterm infants

The attitudes of neonatologists towards the active management of extremely premature infants in a developing country like China are uncertain.