Patrizia Papacci

Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings

PURPOSE To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). DESIGN Single randomized controlled trial. PARTICIPANTS All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. METHODS Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. MAIN OUTCOME MEASURES Presence of retinal and choroidal abnormalities on FA at 9 months. RESULTS Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. CONCLUSIONS This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied.

Original articleIntravitreal Bevacizumab versus Laser Treatment in Type 1 Retinopathy of Prematurity: Report on Fluorescein Angiographic Findings

PURPOSE To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). DESIGN Single randomized controlled trial. PARTICIPANTS All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. METHODS Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. MAIN OUTCOME MEASURES Presence of retinal and choroidal abnormalities on FA at 9 months. RESULTS Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. CONCLUSIONS This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied.

Effects of prophylactic ibuprofen on cerebral and renal hemodynamics in very preterm neonates

To evaluate the effects on cerebral and renal blood flow velocities of ibuprofen when used as prophylaxis for patent ductus arteriosus in preterm neonates (gestational age ≤30 weeks).

Relationship between maternal parity, basal prolactin levels and neonatal breast milk intake

Basal serum levels of prolactin (PRL) in 21 nursing mothers were measured by radioimmunoassay on the 2nd, 3rd and 4th days of the puerperium. The quantity of breast milk suckled during the 4th day of life was also evaluated by calculating the difference in the babys weight before and after each feeding. During the first postpartum days, mean basal levels of PRL did not change. However these levels were noted to be significantly lower in the multiparas (p less than 0.05) than in the primiparas. In addition, the milk intake in neonates of multiparous mothers was significantly greater (p less than 0.05) than that in neonates of primiparous mothers. The authors hypothesis, based on the results of animal experimentation described in the literature, is that initiation of breast-feeding is facilitated in multiparas by the increased number of occupied PRL receptors in the mammary glands reflected by the lowered serum levels of the hormone.

Cardiac Adverse Effects of Early Dexamethasone Treatment in Preterm Infants: A Randomized Clinical Trial

This study evaluates the effects of early administration of dexamethasone on left ventricle dimensions and their clinical significance in preterm infants. Fifty preterm infants with birth weight ≤ 1250 g and gestational age ≤ 30 weeks were randomly assigned after 72 hours of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the 7th day). Serial echocardiographic measurements of end systolic interventricular septum thickness, end diastolic interventricular septum thickness, end systolic left ventricle posterior wall thickness, end diastolic left ventricle posterior wall thickness, left ventricle end diastolic diameter, and left ventricle end systolic diameter were taken before starting dexamethasone, on days 3 and 7 of treatment, 7 days after the interruption of treatment, and at the 28th day of life. Five infants of each group were excluded by the final analysis because of the lack of a complete cardiac evaluation, leaving 20 treated and 20 control infants. Infants receiving dexamethasone had a significantly larger increase in mean septal and left posterior wall thickness during the treatment and 7 days after the dexamethasone weaning. The mean left ventricle diameter of treated infants was significantly lower than that of control infants from the 7th day of treatment to the 28th day of life. Four neonates (20%) in the dexamethasone group developed left ventricular myocardial hypertrophy without left ventricle outflow tract obstruction, showing signs of decreased cardiac output and ischemic changes on ECG. The daily fluid intake was increased to 200 ml/kgto ensure an adequate preload volume, and the complete resolution of left ventricle hypertrophy was obtained within the 2nd to 3rd week after dexamethasone weaning. Preterm infants receiving an early (< 96 hours of life) short course of dexamethasone develop a left ventricular myocardial hypertrophy that can be symptomatic and clinically significant. Preterm infants included in future studies with the goal to find the minimum dose and duration of dexamethasone treatment should be strictly monitored echocardiographically for this side effect.

Use of intravenous ketorolac in the neonate and premature babies

Background : Ketorolac is a powerful nonsteroidal anti‐inflammatory drug widely used for pain control in children and adults. The aim of this study was to evaluate its safety and analgesic efficacy in the neonate.

Failure of fibrinolytic endoventricular treatment to prevent neonatal post-haemorrhagic hydrocephalus. A case-control trial

Abstract Post-haemorrhagic hydrocephalus is assumed to result from obstruction of the cerebrospinal fluid (CSF) pathways by blood clots and subsequent chronic infiltration with collagen. The aim of this work was to evaluate the possibility of preventing permanent shunt dependence by enhancing the endoventricular fibrinolysis by means of an endoventricular streptokinase infusion in babies affected by posthaemorrhagic ventricular dilatation. A case-control trial was carried out in 12 neonates affected by intraventricular haemorrhage and subsequent progressive ventriculomegaly. Six of them were treated with 20,000 U/day of streptokinase infused over 96 h through a percutaneous ventricular catheter. Our results show that the percentage of shunted babies was identical in treated and control patients despite the enhancement of endoventricular fibrinolysis obtained in all treated patients. On the basis of our results we do not recommend intraventricular streptokinase infusion for routine use in post-haemorrhagic ventricular dilatation.

Effect on growth of two different dexamethasone courses for preterm infants at risk of chronic lung disease. A randomized trial.

A randomized study was designed to evaluate the effects of two different dexamethasone courses on the growth of preterm infants. The first phase included 30 preterm infants at high risk for chronic lung disease (CLD). 15 babies (moderately early dexamethasone group) were treated with dexamethasone for 14 days, from the 10th day of life, and received a total dose of 4.75 mg/kg; 15 babies were assigned to the control group. The second phase included 30 preterm infants at high risk for CLD. 15 babies (early dexamethasone group) were treated with dexamethasone for 7 days, from the 4th day of life, and received a total dose of 2.38 mg/kg; 15 babies were assigned to the control group. All the main clinical baseline characteristics were similar between the groups both in the first and in the second phase. Infants given the two dexamethasone courses showed significantly reduced weight gain during the period of treatment when compared to the respective control group, but they had a weight catch-up soon after the end of treatment. At 30 days of life the weight and length gain of each treated group were similar to those of control infants, but the moderately early dexamethasone group showed a significantly poorer head growth. No differences between the groups were observed at discharge. Dexamethasone treatment induces a slower weight gain which is time-limited to the period of treatment and is followed by a body weight catch-up. However, the poorer head growth detected at 30 days of life in the infants who received a higher dose of dexamethasone could indicate important adverse effects, possibly dose-related, on postnatal brain growth and development.

A prospective, randomized, double blind study comparing lutein to placebo for reducing occurrence and severity of retinopathy of prematurity

Lutein has been shown to have antioxidant functions in newborns and with zeaxantin selectively taken up into the macula of the eye. We hypothesize that lutein administration may contribute to reducing the incidence of Retinopathy of Prematurity (ROP). This was a single center, double-blind randomized controlled study. Preterm infants with gestational age (GA) ≤32 weeks able to tolerate minimal enteral feeding before the seventh day of life (DOL) were enrolled; lutein and zeaxantin plasma concentrations and ROP occurrence and severity were evaluated. Sixty-three newborns were enrolled, 31 in the lutein group and 32 in the placebo group (one died before ROP assessment). The mean GA was 29.9 (±1.9) weeks and the mean birth weight was 1331 (±415) grams. There were no differences in the incidence of ROP at any stage between groups. Oxidative injury is probably an additional mechanism of damage of the developing retinal vessels, and it probably plays only a minor role in the pathogenesis of ROP. Supplementation with antioxidant substances might have beneficial effects noticeable only on larger samples of high risk neonates or at very high dosage. Further investigations would be needed to evaluate whether lutein supplementation can influence functional rather than anatomical outcomes in preterm infants.

Spontaneous minute ventilation is a predictor of extubation failure in extremely-low-birth-weight infants

Objective: To validate the percentage of time spent below a target value of spontaneous expiratory minute ventilation (<125 ml/min per kg) during a 2-h period of continuous positive airway pressure (CPAP) via an endotracheal tube (ETT) as a predictor of failed extubation in preterm infants.Methods: Forty-one infants intubated for at least 24 h, with birth weight between 500 and 1000 g, who were clinically stable and at ventilator setting compatible with an extubation attempt, were studied during a 2-h period of ETT CPAP. Dynamic lung compliance and total lung resistance were measured during a period of quiet breathing, while tidal volume (Vt), respiratory rate and the corresponding spontaneous expiratory minute ventilation values were calculated for the complete recording period of 2 h using a customized computer program. The time each patient spent below the target spontaneous expiratory minute ventilation value was reported as a percentage of the total recorded time (% spontaneous expiratory minute ventilation <125 ml/min per kg). Extubation failure was defined as the need for reintubation within 72 h.Results: Eleven out of 41 babies (26.8%) experienced failure of extubation (failure group) while 30 infants (73.2%) were successfully extubated (success group). There were no significant differences in dynamic lung compliance and lung resistance between the two groups, but the mean values of respiratory rate and spontaneous expiratory minute ventilation were significantly lower in the failure group than in the success group: 43 (37–56) breaths/min and 240 (160–353) ml/min per kg vs. 53 (28–67) breaths/min and 309 (223–434) ml/min per kg, respectively (p=0.0129 and p=0.0039). Moreover, the babies in whom extubation failed spent a longer time below the target value of spontaneous expiratory minute ventilation when compared with successfully extubated babies (p<0.0001). Percentage of time spent with spontaneous expiratory minute ventilation <125 ml/min per kg had a larger area than transcutaneous (Tc)PCO2, TcPO2and pulse oxymetry saturation (SpO2) under the receiver operator characteristic curves.Conclusion: The measurement of spontaneous expiratory minute ventilation prior to extubation could be useful in identifying those babies who are not ready for spontaneous ventilation.