Are high cumulative doses of erythropoietin neuroprotective in preterm infants? A two year follow-up report.

BACKGROUND: Preterm infants are at risk for neurodevelopmental sequelae even in absence of major cerebral lesions. The hypothesis that Human Recombinant Erythropoietin (rEpo) could improve the neurodevelopmental outcome in risk neonates has raised the highest interest in recent years. METHODS: A group of preterm neonates born at a gestational age ≤ 30 weeks and free from major cerebral lesions or major visual impairment, were included in the study if they had a complete neurologic evaluation for at least 24 months of postmenstrual age. They were assigned to group I in the case they had been treated with rEpo or group II if untreated. The aim was to evaluate whether rEpo, given at the high cumulative doses utilized for hematologic purposes, is able to improve the neurodevelopmental outcome in preterm infants born at a gestational age ≤ 30 weeks. A group of 104 preterm neonates were studied: 59 neonates who received rEpo for 6.9 ± 2.4 weeks at a median cumulative dose of 6300 UI/Kg (6337 ± 2434 UI/Kg), starting at a median age of 4 days and 45 neonates who were born in the period preceding the routine use of rEpo. The neurodevelopmental quotient at 24 month postmenstrual age was assessed utilizing the Griffiths' Mental Developmental Scales. RESULTS: Our results failed to show any difference in the Developmental Quotient at 24 month. Bronchopulmonary dysplasia, minor intraventricular hemorrhages and blood transfusions were the clinical features significantly related to the Developmental Quotient. CONCLUSIONS: Our results do not support the hypothesis that rEpo, administered with the schedule utilized for hematologic purposes, improve the neurodevelopmental outcome of preterm neonates, at least those preterm infants free from major impairments.

Neurodevelopmental outcomes of premature infants with bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disorder common among very preterm infants affecting significantly not only mortality and morbidity but also neurodevelopmental outcomes. This review aims to identify the short and long-term neurodevelopmental outcomes of infants with BPD, considering that the new definition of BPD allows to relate severity of BPD with greater risk of developmental delay.

Urinary aldosterone excretion and electrolytic balance in response to chronic diuretic therapy in very low-birth weight infants.

BACKGROUND: It has been reported that the reninangiotensin- aldosterone system of healthy newborn infants and pre-term infants responds to acute furosemide challenge. OBJECTIVE: To assess urinary aldosterone excretion (UAE) and electrolytic balance in very low-birth weight (VLBW) infants who received chronic therapy with furosemide and to compare them with those of infants who did not receive diuretic therapy. METHODS: Infants with birth weight <1500 g were considered eligible for this prospective observational study. On the 10th day of life, infants enrolled were divided in 2 groups on the basis of our predictive score for chronic lung disease (CLD): group 1, with positive score, received furosemide and group 2, with negative score, did not receive diuretic therapy. Urinary aldosterone and electrolytes excretion, electrolytes intakes and clearance of creatinine were investigated before the beginning of the treatment and then weekly until discharge in both groups, and results were compared. RESULTS: Thirty infants were studied: 15 received long-term furosemide and 15 did not. UAE progressively increased in infants who received furosemide whereas remained unchanged in infants who did not receive treatment. UAE was greater in group 1 than in group 2 after 3 weeks of diuretic treatment, reaching statistical significance after 4 weeks of treatment. CONCLUSIONS: In VLBW infants, chronic therapy with furosemide leads to a progressive increase in UAE that may potentially limit the diuretic effect of long-term use of furosemide in the management of CLD.

Respiratory disorders and hospitalization rates during the second RSV season in preterm infants who received palivizumab prophylaxis during their first RSV season.

This prospective study evaluated the frequency and severity of respiratory symptoms during the second respiratory syncytial virus (RSV) season in an italian cohort of preterm infants (< or = 35 weeks) who had received palivizumab prophylaxis in their first year of life (October 2004-April 2005) and who had not previously been hospitalized for RSV-induced lower respiratory tract infection (LRTI). infants were evaluated at enrolment (May-September 2005), in October/November 2005 and in April 2006. The occurrence of any respiratory episode, the rate of hospitalization for respiratory-related LRTI, total length of stay in hospital, physician-documented recurrent wheezing (>or = 3 physician-documented episodes of wheezing) and use of airway medication/antibiotics were recorded during follow-up. All infants had prior palivizumab prophylaxis during their first RSV season. In the total evaluable population (n=260), 32.3% of infants experienced at least one respiratory episode, 3.8% required short hospitalization because of LRTI, 8.5% had physician-documented recurrent wheezing, and 48.8% required airway medications/antibiotics during follow-up. in this study the rate of airway morbidity, hospitalization and physician-documented recurrent wheezing during the second RSV season was low among preterm infants who had received prior palivizumab prophylaxis.

Urinary aldosterone excretion and renal function in extremely-low-birth-weight infants following acute furosemide therapy.

BACKGROUND: Increased activity of the renin-angiotensin-aldosterone system (RAAS) has been reported in the neonatal period. Until now, it has been demonstrated that the RAAS of healthy neonates responds to acute furosemide challenge while no data concerning the responsiveness of RAAS in extremely low birth weight (ELBW) infants are available. OBJECTIVE: To assess urinary aldosterone excretion (UAE) and renal function in ELBW infants who received diuretics for the purpose of reducing the incidence of chronic lung disease (CLD). METHODS: Infants with birth weights < or =1,000 g, at high risk to develop CLD, were studied in a prospective observational study. UAE and renal function were investigated before and after administration of furosemide given in a single dose of 2 mg/kg. RESULTS: UAE and renal function were evaluated in 20 ELBW infants. Diuretic administration resulted in a significant rise in UAE and urinary sodium, potassium and chloride excretion. No change occurred in creatinine clearance, while urine volume increased significantly. CONCLUSIONS: ELBW infants respond to acute furosemide challenge by increasing urine volume, urinary electrolytes and UAE.

Antenatal post-hemorrhagic ventriculomegaly: a prospective follow-up study.

OBJECTIVE: The aim of this study was to evaluate the presence and the severity of neurological and cognitive impairment at 2 years of age in 16 infants (9 term born, 7 preterm of mean gestation 33.6 weeks) with cerebral ventriculomegaly of antenatal onset associated with intraventricular haemorrhage. METHODS: Ventricular dilatation, with or without associated lesions, was, with one exception, not identified on the antenatal routine scan at approximately 22 weeks but was obvious on the scans performed between weeks 27 and 33. In 8 of the 16 cases there were signs of parenchymal involvement or of abnormalities of the corpus callosum or cerebellum. In all patients the diagnosis of antenatal IVH was confirmed by early neonatal imaging. Outcome was measured using the Hammersmith infant neurological examination and the Griffiths developmental scales at 2 years. RESULTS AND CONCLUSIONS: At 2 years, 8 infants had normal motor outcome and 8 had cerebral palsy. The presence and severity of cerebral palsy or neurodevelopmental delay was not always related to the magnitude or symmetry of the ventricular dilatation per se. The presence of associated lesions was a negative prognostic marker. The early development of epilepsy was also associated with an abnormal outcome.

Neurological examination at 6 to 9 months in infants with cystic periventricular leukomalacia.

The Hammersmith Infant Neurological Examination was performed in 24 infants with cystic periventricular leukomalacia whose gestational age ranged between 26-38 weeks. The infants were examined between 6 and 9.5 months corrected age. The aim of the study was to establish the different patterns of neurological abnormality as well as the optimality scores that predict the severity of motor sequelae at 2 years. Increased neck and trunk extensor tone, and a posture of flexed arms and extended legs between 6 and 9 months were always associated with the inability to sit unsupported at 2 years, whilst truncal hypotonia and extended arms and legs were associated with unsupported sitting but not walking. Optimality scores between 41 and 60 were generally associated with sitting but not walking at 2 years whilst scores below 40 were always associated with the inability to sit independently at 2 years. All infants who did not develop cerebral palsy at 2 years had scores > 60. Our results suggest that the pattern of findings on neurological examination performed between 6 and 9 months as well as the calculated optimality score helps to predict motor impairment in infants with PVL.

Crossed cerebellar atrophy of prenatal onset.

BACKGROUND: Crossed cerebellar atrophy after hemorrhagic-ischemic injury in the contralateral cerebral hemisphere was reported in adults with stroke and in children with acquired lesions. It was also reported in preterm infants after perinatal or postnatal contralateral supratentorial lesions. CASE REPORT: We report crossed-cerebellar atrophy in a preterm neonate with prenatal posthemorrhagic ventriculomegaly and periventricular ischemic lesion in whom contralateral cerebellar involvement was detected on antenatal scans. DISCUSSION: The result of our study suggests that in the developing brain, cross cerebellar atrophy may occur antenatally and that fetal MRI may help to identify such cases.

Cerebral ultrasound findings in neonatal lupus syndrome.

A prospective study was performed enrolling 11 newborns with neonatal lupus syndrome (NLS) and 22 control newborns to investigate cerebral ultrasound (US) anomalies and their relationship with clinical neurological signs and laboratory findings. Cerebral US detected a significantly higher incidence in the study group of both subependymal pseudocysts (SEPC) and subependymal hemorrhage (SEH), neither of which correlated to autoantibody levels. All infants had completely normal neurological examinations both at birth and follow-up. The etiopathogenesis of central nervous system findings in NLS is discussed. US evaluation identified minimal anomalies compatible with favorable outcome: further studies are necessary to investigate the possible long-term sequelae, pathogenesis and spectrum of cerebral US findings.

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 < or = 1250 g and gestational age < or = 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/kg to 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.

Progression of renal function in preterm neonates with gestational age < or = 32 weeks.

Serum creatinine (SeCr), creatinine clearance (CrCl), and fractional excretion of sodium (FeNa) were measured in 83 preterm neonates divided into four groups according to gestational age (GA). At birth, there were no differences in mean SeCr values in the four groups nor any significant correlation between initial values and GA. In all groups there was an initial SeCr increase; an inverse correlation between SeCr and GA was observed from the 3rd day of life to the 5th week (p<0.001). CrCl showed a positive correlation to GA from the first week onwards (p<0.001); in each group CrCl values correlated positively to days of life (p=0.0001). Rate of CrCl increase correlated positively to GA (p=0.0005). FeNa showed an inverse correlation to GA from the first week (p<0.001). In each group, the FeNa value correlated negatively to postnatal age (p<0.001) and the velocity of decrease was directly correlated to GA (p=0.0358). Our findings indicate that glomerular function shows a progression directly correlated to GA and postnatal age, while tubular function correlates inversely to the same parameters. The values reported could be useful for following renal function in very low birth weight infants.

Do recombinant human erythropoietin and iron supplementation increase the risk of retinopathy of prematurity?

Comparing a group of infants treated with recombinant erythropoietin and iron supplementation to a group of control infants, no difference was observed concerning the transfusion need. The incidence of retinopathy of prematurity was significantly higher in the treated group. These data need to be confirmed in randomized controlled studies.

Doppler evaluation of renal blood flow velocity as a predictive index of acute renal failure in perinatal asphyxia.

UNLABELLED: Aim of our study was to evaluate Doppler renal blood flow velocity in asphyxiated neonates and to correlate renal function to Doppler findings. Doppler renal blood flow velocity was evaluated in 23 severely asphyxiated neonates born at a gestational age > 32 weeks and compared to our standard Doppler data obtained in 25 healthy neonates comparable for gestational age and birth weight. Renal Doppler ultrasound was performed on the 1st and 3rd days of life. Renal function was investigated in the first 2 weeks of life. Asphyxiated neonates showed mean values of systolic velocity and mean velocity significantly reduced (P < 0.001) compared with our standard Doppler values on the 1st day of life. Seven out of the 23 asphyxiated neonates were affected by acute renal failure and 14 showed no renal involvement. Two neonates were oliguric but did not develop acute renal failure. On the 1st day of life, neonates with acute renal failure had significantly lower mean values of systolic velocity and mean velocity than the asphyxiated neonates without renal involvement (P < 0.01). All 7 neonates affected by acute renal failure showed a systolic velocity more than 2SD below the mean standard value, while only 4 of the 16 asphyxiated neonates (25%) without acute renal failure had low systolic velocity values on the 1st day of life. Doppler velocities in asphyxiated neonates were similar to standard values on the 3rd day of life. Renal failure recovered before the 11th day of life in all cases. CONCLUSION: Our findings indicate that decreased Doppler renal flow systolic velocity observed in asphyxiated neonates on the st day of life is a useful predictive index for subsequent development of acute renal failure, with 100% sensitivity and 63.6% specificity.

Furosemide does not prevent indomethacin-induced renal side effects in preterm infants.

OBJECTIVE: To determine whether furosemide could prevent renal side effects of indomethacin (INN, indometacin) used for the pharmacologic closure of the patent ductus arteriosus (PDA) in preterm infants. METHODS: Thirty-six preterm infants with birth weights < 1750 gm affected by hemodynamically significant PDA were randomly assigned to one of two study groups. Group 1 consisted of 18 infants treated with three doses of indomethacin (0.20 mg/kg every 12 hours); each dose was followed by a dose of furosemide (1 mg/kg). Group 2 consisted of 18 infants treated only with the same doses of indomethacin. Body weight, urine output, glomerular filtration rate (GFR), fractional excretion of sodium (FENa+) and potassium (FEK+), and osmolal and free water clearance were evaluated in both groups before, during, and after treatment. RESULTS: The body weight trend, serum sodium, chloride and potassium concentrations, plasmatic and urinary osmolality were similar during the treatment in both the groups. A significant reduction of urine output (p < 0.01) was detected in group 2 but not in group 1. A significant increase of blood urea nitrogen and serum creatinine was detected at the end of treatment in group 1 compared with group 2. During the treatment, a significantly higher GFR (p < 0.05) was found in group 2 than in group 1. FENa+ and FEK+ were significantly higher (p < 0.05 and p < 0.001, respectively) in group 1 than in group 2 during and after the treatment. The osmolol clearance and free water clearance were significantly higher during and after treatment (p < 0.01 and p < 0.001, respectively) in group 1 than in group 2. CONCLUSIONS: Our findings show that furosemide cannot prevent the indomethacin-induced renal failure, but it does not have any negative influence on its therapeutic effectiveness.

Fetal encephalopathy after maternal anaphylaxis. Case report.

Fetal hypoxic-ischemic encephalopathy can be diagnosed at birth by means of cerebral ultrasound scanning. The morphological appearance of the lesions depends on the time elapsed between the insult and examination of the brain. We report a case of a neonate affected by multicystic encephalomalacia and corpus callosum atrophy attributable to an episode of maternal anaphylactic shock which occurred at 27 weeks of gestation following intravenous iron injection. The diagnosis was made by means of a cerebral ultrasound scan performed at birth and confirmed by magnetic resonance. This case demonstrates that maternal severe acute hypotension during pregnancy can cause fetal cerebral damage similar to the hypoxicischemic injuries occurring in the perinatal period.

[Caloric intake in parenteral nutrition of very low weight infants]. / Rendimento calorico della nutrizione parenterale nel neonato di peso molto basso.

To evaluate the efficacy of a measure able to compare energy intake from parenteral and enteral nutrition we documented growth patterns in a group of VLBW infants treated with parenteral nutrition (PN). To analyze comparative energy intake from the two sources we expressed a percentage of both parenteral and enteral calories: the former (RCP%) related to an optimal value of 85 non protein calories and the latter (RCE%) to an optimal value of 150 total calories. Total energy intake was planned on the RCT% (RCP% + RCE%). We studied 75 VLBW infants with a mean BW of 1040 g and a mean GA of 29.5 weeks. The mean duration of PN was 25.8 +/- 10.4 days. The initial weight loss (10.2 +/- 5.3%), the time to regain BW (5.5 +/- 4 days) and the day of lowest weight (5.2 +/- 1.6 day of life) were in the normal range; the subsequent growth rate resulted 25.9 +/- 9.2 g/kg/die and did not change for different GA or BW. Growth pattern about head circumference and length were above the third percentile. The mean age of RCT% = 100% was 11.4 +/- 4.8 days of PN; this value was higher for the more premature infants. Severe metabolic abnormalities were not detected. Our observations show the efficacy of the RCT% as index of energy from both enteral and parenteral source during PN: the growth pattern seems to be quite satisfactory without any severe metabolic complication.

[Weight gain in the first 2 months of life in neonates with a birth weight less than or equal to 1500 g. A comparison between parenteral nutrition and orogastric feeding]. / Accrescimento ponderale dei primi due mesi di vita in neonati con PN meno di od uguale a 1500 g. Confronto tra nutrizione parenterale e alimentazione orogastrica.

This study was designed to verify the effectiveness of parenteral nutrition (NP) and continuous nasogastric feeding (AOG) in providing a good caloric intake and a good growth in the very low birth weight infants during the first 60 days of life. The study included 108 preterm babies with birth weight less than or equal to 1500 g: 26 received parenteral nutrition, 82 nasogastric feeding. Infants in NP showed a smaller postnatal weight loss and regained birth weight earlier than the AOG group. Caloric intake greater than 120 kcal/kg/die was achieved in 10.2 days of life in the NP group and in 14.1 days in the AOG group. Full enteral feeding was achieved later in the NP than in the AOG group (25.7 days vs 20.7 days). Weight gain at 60 days of life was better in the NP group (23.2 g/die vs 18.2 g/die), while there was no difference in the head circumference gain. The study shows the efficacy of NP in providing a good caloric intake in the very low birth weight infants in the first weeks of life.

[Osteopenia of prematurity. Proposal for clinical-laboratory screening]. / L'osteopenia della prematurità. Proposta di uno screening clinico-laboratoristico.

Osteopenia is a metabolic bone disease which affects a great deal of preterm infants. X-Ray evaluation is still the main step of the diagnostic and follow-up procedures. The Authors prospectively studied 77 newborn infants with birth weight less than 2500 grams, to identify specific clinical and biochemical features of the osteopenic infants. From the 2nd to the 12th week of life clinical, biochemical and radiological signs of osteopenia were looked for, every 2 weeks: the diagnosis of osteopenia was made on the basis of X-Ray. 26 osteopenic subjects with ga less than or equal to 32 weeks and/or bw less than or equal to 1500 grams were compared with 20 controls with ga less than or equal to 32 weeks and/or bw less than or equal to 1500 grams and with 31 control infants with ga greater than 32 weeks and bw greater than 1500 grams. Wider anterior funtanels, their progressively increasing dimensions, and craniotabe (with the "ping pong ball" sign) were the most characteristic features, as well as the increasing pattern of alkaline phosphatase activity, of the osteopenic babies. The Authors suggest a specific clinical and biochemical score to make the correct diagnosis and a non invasive follow-up in the osteopenic subjects and to avoid dangerous X-Ray exposure to babies that are not osteopenic.