Chiara Poggi

Topiramate concentrations in neonates treated with prolonged whole body hypothermia for hypoxic ischemic encephalopathy

Purpose:  Therapeutic hypothermia reduces mortality and neurologic impairment in neonates with hypoxic–ischemic encephalopathy. Topiramate exerts a neuroprotective effect in asphyxiated neonatal animal models. However, no studies have investigated the association of hypothermia and topiramate, because topiramate pharmacokinetics during hypothermia and the optimal administration schedule are unknown. The influence of hypothermia on topiramate pharmacokinetics was evaluated in asphyxiated neonates treated with prolonged whole‐body hypothermia and topiramate.

Oral Topiramate in Neonates with Hypoxic Ischemic Encephalopathy Treated with Hypothermia: A Safety Study

OBJECTIVE To investigate whether topiramate associated with mild or deep hypothermia in asphyxiated term infants is safe in relation to the short-term outcome. STUDY DESIGN We report on 27 consecutive asphyxiated newborns who were treated with whole body hypothermia and 27 additional consecutive newborns with hypothermia who were co-treated with oral topiramate, once a day for 3 consecutive days, at 2 different doses. RESULTS Newborns were divided in 6 groups according to the depth of hypothermia and the association with higher or lower topiramate dosage. A statistical comparison of the groups identified some differences in biochemical and hemodynamic variables, but no adverse effects attributable to topiramate were detected. There were no statistically significant differences in the groups in short-term outcomes, survival rate at discharge, or incidence of pathologic brain magnetic resonance imaging. CONCLUSION Although the number of newborns in this study was limited, the short-term outcome and the safety data appear to support the evaluation of topiramate in clinical trials to explore its possible additive neuroprotective action.

Dopamine versus dobutamine in very low birthweight infants: endocrine effects

Objectives: To compare the endocrine effects of dopamine and dobutamine in hypotensive very low birthweight (VLBW) infants. Design: Non-blinded randomised prospective trial. Setting: Level III neonatal intensive care unit. Patients: 35 hypotensive VLBW infants who did not respond to volume loading, assigned to receive dopamine or dobutamine. Measurements: Haemodynamic variables and serum levels of thyroid stimulating hormone (TSH), total thyroxine (T4), prolactin (PRL) and growth hormone were assessed during the first 72 h of treatment and the first 72 h after stopping treatment. Results: Demographic and clinical data did not significantly differ between the two groups. Necessary cumulative and mean drug doses and maximum infusion required to normalise blood pressure were significantly higher in the dobutamine than in the dopamine group (p<0.01). Suppression of TSH, T4 and PRL was observed in dopamine-treated newborns from 12 h of treatment onwards, whereas levels of growth hormone reduced significantly only at 12 h and 36 h of treatment (p<0.01). TSH, T4 and PRL rebound was observed from the first day onwards after stopping dopamine. Dobutamine administration did not alter the profile of any of the hormones and no rebound was observed after stopping treatment. Conclusion: Dopamine and dobutamine both increase the systemic blood pressure, though dopamine is more effective. Dopamine reduces serum levels of TSH, T4 and PRL in VLBW infants but such suppression is quickly reversed after treatment is stopped. Further research is required to assess if short-term iatrogenic pituitary suppression has longer-term consequences.

Method of delivery and intraventricular haemorrhage in extremely preterm infants

Objectives. It has been reported that caesarean delivery (CD) protects against intraventricular haemorrhage (IVH) in the extremely preterm infant, but it is not known whether this effect involve the more severe grades of IVH. Thus, our aim was to confirm the correlation between the occurrence of IVH and the mode of delivery, and to evaluate this correlation for each grade of IVH. Methods. All infants with gestational age (GA) ≤ 28 weeks admitted to the neonatal intensive care unit of a tertiary hospital were studied for each grade IVH and major complications rate. Results. We found that vaginally born infants had a higher rate of each grade of IVH, but the increase was statistically significant only for grade 3 IVH (18% vs. 2%, p < 0.0001) and all grades IVH (45% vs. 20%, p < 0.0001). Multivariate analysis demonstrated that CD (RR: 0.42, 95% CI 0.28–0.63), birth weight ≥ 800 g (RR: 0.48, 95% CI 0.32–0.73), 27–28 weeks of GA (RR: 0.38, 95% CI 0.25–0.60) and antenatal steroids (0.66, 95% CI 0.22–0.46) decrease independently the risk of developing IVH. Conclusions. Our study demonstrates that CD decreases the risk of developing IVH in extremely preterm infants including the most severe grades of IVH.

Fusidic acid and heparin lock solution for the prevention of catheter-related bloodstream infections in critically ill neonates: a retrospective study and a prospective, randomized trial.

Objective: Catheter-related bloodstream infections (CRBSIs) are one of the main morbidities in critically ill neonates. The objective of the present study was to assess the efficacy of a fusidic acid-heparin lock in the prevention of CRBSIs. Design: A preliminary retrospective study showed that staphylococcal infections were largely prevalent. We planned a prospective, randomized trial to ascertain whether fusidic acid and heparin lock of central venous catheters would reduce the incidence of CRBSIs. Setting: Level III neonatal intensive care unit. Patients: One hundred three neonates were enrolled and randomly assigned to a treatment group (n = 50) or control group (n = 53). Interventions: Fusidic acid (4 mg/mL) and heparin (10 IU/mL) lock in the treatment group. Measurements and Main Results: The treatment group showed significantly lower incidence of CRBSIs (6.6 vs. 24.9 per 1000 catheter days; p < .01; relative risk 0.28; 95% confidence interval 0.13–0.60). No staphylococcal infections occurred in the treatment group, while in the control group Staphylococcus remained the main agent of CRBSI. Cost analysis comparing the present study and for the treatment of CRBSIs proved that antibiotic lock is financially favorable. Conclusions: Fusidic acid-heparin lock solution reduced the incidence of CRBSIs in our neonatal intensive care unit. However, we recommend basing antibiotic lock on local CRBSI epidemiology. With regard to fusidic acid, further and broader studies could be useful to confirm our results.

Use of polyvinyl feeding tubes and iatrogenic pharyngo-oesophageal perforation in very-low-birthweight infants

BACKGROUND Placement of a feeding tube may be associated with various complications, including iatrogenic pharyngo-oesophageal perforation. AIM To determine the incidence of pharyngo-oesophageal perforation secondary to the use of polyvinyl feeding tubes in newborns weighing less than 1500 g, we conducted a retrospective study over a 3(1/2)-y period. METHODS All the hospital files of the 371 very-low-birthweight newborns admitted were retrospectively reviewed. RESULTS Three iatrogenic pharyngo-oesophageal perforations were observed, giving an incidence of 1:124 preterm infants. This incidence reaches values of 1:25 newborns weighing less than 750 g. Data from our cases included clinical presentation and outcome, radiological evaluation, and type of feeding tube. One infant died of sepsis, and the clinical course was compatible with mediastinitis. The other two infants were treated successfully with conservative non-surgical management. CONCLUSION Pharyngo-oesophageal perforation in our experience exclusively involved preterm infants weighing less than 750 g after traumatic placement of a polyvinyl feeding tube. The use of a silastic feeding tube with a really soft end instead of polyvinyl catheters could probably avoid iatrogenic oesophageal perforation.

Nutrition and bronchopulmonary dysplasia

We aimed to assess the current knowledge on the nutritional management of preterm infants at risk of developing bronchopulmonary dysplasia (BPD) or with BPD. We considered the evidence supporting the actual fluid and energy intake, proteins, lipids, and electrolytes requirement, and need for other nutrients in preterm infant at risk of developing BPD or with BPD. We concluded that, although many areas remain to be investigated, early nutrition support and careful adjustment of parenteral nutrition and appropriate enteral feeding selection may enhance the growth and contribute a better neurodevelopment in these patients.

Coagulopathy screening and early plasma treatment for the prevention of intraventricular hemorrhage in preterm infants.

BACKGROUND: Despite the improvement in the assistance and treatment of preterm infants, intraventricular hemorrhage (IVH) remains a frequent complication in these patients. Our aim was to demonstrate the hypothesis that a coagulopathy screening and the early treatment with fresh‐frozen plasma (FFP) of proven coagulopathy may contribute to decrease the occurrence of IVH in infants with gestational age of less than 29 weeks.

Antioxidant Strategies and Respiratory Disease of the Preterm Newborn: An Update

Preterm newborns are challenged by an excessive oxidative burden, as a result of several perinatal stimuli, as intrauterine infections, resuscitation, mechanical ventilation, and postnatal complications, in the presence of immature antioxidant capacities. “Oxygen radical disease of neonatology” comprises a wide range of conditions sharing a common pathway of pathogenesis and includes bronchopulmonary dysplasia (BPD) and other main complications of prematurity. Antioxidant strategies may be beneficial in the prevention and treatment of oxidative stress- (OS-) related lung disease of the preterm newborn. Endotracheal supplementation or lung-targeted overexpression of superoxide dismutase was proved to reduce lung damage in several models; however, the supplementation in preterm newborn failed to reduce the risk of BPD, although long-term respiratory outcomes were improved. Also melatonin administration to small cohorts of preterm newborns suggested beneficial effects on lung OS. The possibility to identify single nucleotide polymorphism affecting the risk of BPD may help to identify specific populations with particularly high risk of OS-related diseases and may pose the basis for individually targeted treatments. Finally, surfactant replacement may lead to local anti-inflammatory and antioxidant effects, thanks to specific enzymatic and nonenzymatic antioxidants naturally present in animal surfactants.

Genetic polymorphisms of antioxidant enzymes as risk factors for oxidative stress-associated complications in preterm infants

Abstract We aimed to identify specific polymorphisms of genes encoding for superoxide dismutase (SOD) 1 (cytoplasmic Cu/ZnSOD), SOD2 (mitochondrial MnSOD), SOD3 (extracellular Cu/ZnSOD) and CAT in a cohort of preterm infants and correlate their presence to the development of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH) and retinopathy of prematurity (ROP). We carried out a retrospective study to evaluate the allele frequency and the genotype distribution of polymorphisms of SODs and CAT in a population of preterm neonates (n = 152) with a gestational age ≤ 28 weeks according to the presence or absence of RDS, BPD, IVH and ROP. Moreover, we evaluated through the haplotype reconstruction analysis whether combinations of the selected polymorphisms are related to the occurrence of RDS, BPD, IVH and ROP. We found that rs8192287 SOD3 polymorphism is an independent protective factor for all grade IVH, while rs4880 and rs5746136 SOD2 polymorphisms are associated with a lower gestational age (rs4880, rs5746136) and birth weight (rs4880). Haplotypes reconstruction showed that SOD1 (GG) decreased the risk of RDS, IVH and ROP; SOD2 (GT) increased the risk of BPD and decreased the risk of RDS, IVH and ROP; SOD3 (TGC) decreased the risk of BPD and IVH; and 4) CAT (CTC) decreased the risk of RDS. The rs8192287 SOD3 polymorphism is per se an independent predictor of a decreased risk of developing IVH. Different SOD2 polymorphisms are associated per se with a lower gestational age and/or birth weight, and haplotypes of SOD1, SOD3 and CAT genes may be independent protecting or risk markers for prematurity complications.