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.

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

OBJECTIVE: 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). METHODS: Blood flow velocities in the anterior cerebral artery and the renal artery were measured with Doppler ultrasonography in 17 neonates before, during, and 10, 30, and 60 minutes after administration of 10 mg/kg ibuprofen lysine. RESULTS: In four (23.6%) neonates without echocardiographic patency of the ductus, no significant modifications in blood flow velocities and Doppler indexes were found either in the anterior cerebral artery or in the renal artery. In 13 (76.4%) neonates, cardiac echocardiographic Doppler showed patency of the ductus and left-to-right shunt. In these neonates diastolic and mean blood velocities rapidly increased both in the anterior cerebral artery and the renal artery (P < .0001). Resistance and pulsatility index decreased during the study period (P < .0001 and P < .001, respectively, in the anterior cerebral artery; P < .0001 in the renal artery). CONCLUSIONS: Data suggest that ibuprofen does not determine any direct effect on cerebral and renal blood flow velocities; hemodynamic modifications observed in neonates with patency of ductus can be related to closure of the ductus induced by the drug.

Antithrombin III in full-term and pre-term newborn infants: three cases of neonatal diagnosis of AT III congenital defect.

Antithrombin III (AT III) plasma levels were investigated in 18 full term neonates and 14 healthy preterm neonates. A control group of 20 healthy adults was also studied. AT III was measured as antigen concentration (Ag) and antithrombin or anti-factor Xa heparin cofactor (H.C.) activities. Crossed immunoelectrophoresis on heparin-agarose (H-CIE) was carried out on plasma samples; moreover the distribution of isoantithrombins was investigated on whole plasma by a technique of crossed immunoelectrofocusing (CIEF). AT III plasma levels in full term infants were significantly lower as compared to the adult values. The preterm newborns group showed a further significant decrease in AT III levels as compared to the full term neonates. In all infants AT III H-CIE runs displayed a single fast moving anodal peak, so that a normal binding to heparin was demonstrated. The CIEF AT III plasma pattern of the adults as well as of all neonates displayed three major peaks at pH range 5.2-4.9, a small amount of AT III at pH 4.9-4.8 and a minor peak at pH 4.8-4.6, so that it was concluded that the isoantithrombins plasma distribution in neonatal age is identical to that of the adult subjects. Four neonates whose mothers were affected by AT III congenital defect were also investigated: diagnosis of congenital deficiency was established in three cases.

A scoring system to predict the evolution of respiratory distress syndrome into chronic lung disease in preterm infants.

OBJECTIVE: The purpose of this study was to develop and validate an empirical scoring system to predict the evolution of neonatal respiratory distress syndrome (RDS) into chronic lung disease (CLD) in preterm infants, by comparing it with a more complicated logistic regression model. DESIGN: Clinical study. SETTING: Neonatal intensive care unit. PATIENTS: The retrospective analysis of a 3-year experience showed that a gestational age (GA) of less than 30 weeks, a birth weight (BW) of less than 1000 g, the diagnosis of hyaline membrane disease (HMD) and pulmonary interstitial emphysema (PIE) during the first 72 h of life, the peak inspiratory pressure (PIP) and the fraction of inspired oxygen (FIO2) were the highest relative risk factors correlated with the evolution of CLD. On this basis an empirical and a statistical scoring system were defined and prospectively applied at 3 and 5 days of life to 228 neonates with BW less than 1,250 g. The results obtained with both scoring systems were then compared. RESULTS: Of the 149 infants surviving at 28 days of life, 67 (GA: 29.9 +/- 2.3 weeks; BW: 1,058 +/- 143 g) were normal and 82 (GA: 27.5 +/- 3.9 weeks: BW: 838 +/- 200 g) had CLD. Using a cut-off value of 4.0, the empirical scoring system showed a specificity of 97.0% and a sensitivity of 92.7% on the 3rd day of life; on the 5th day of life the specificity was still 95.5%, while sensitivity remained 92.7%. The areas under the ROC curves plotted with both scoring systems tested were similar. CONCLUSIONS: The proposed empirical scoring system is easy to use and is highly reliable. The application of this scoring system provides the opportunity to direct aggressive treatment for CLD toward only very high risk patients between the 3rd and 5th days of life.

Early postnatal dexamethasone for the prevention of chronic lung disease in high-risk preterm infants.

OBJECTIVE: The purpose of this study was to evaluate the effect of early administration of dexamethasone on the incidence of chronic lung disease (CLD) in high risk preterm infants and to evaluate the side effects of the early steroid administration. DESIGN: Randomised clinical trial. SETTING: Neonatal intensive care unit. PATIENTS: 50 infants at high risk of CLD were randomly assigned after 72 h 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 per day for the first 3 days, 0.25 mg/kg per day for the next 3 days and 0.125 mg/kg per day on the 7th day). The control group received no steroid treatment. RESULTS: The incidence of CLD at 28 days of life and at 36 weeks' postconceptional age was significantly lower in the dexamethasone group than in the control group (p < 0.001). Moreover, infants in the dexamethasone group remained intubated and required oxygen therapy for a shorter period than those in the control group (p < 0.001). Hyperglycaemia, hypertension, growth failure and mainly hypertrophy of the left ventricle were the transient side effects associated with early steroid administration. CONCLUSIONS: Early dexamethasone administration may be useful in preventing CLD, but its use should prudently be restricted to preterm infants at high risk of CLD.

Doppler ultrasound of blood flow velocities in ophthalmic and central retinal arteries during the early neonatal period.

PURPOSE: To obtain standard values of blood flow velocity in the ophthalmic artery and central retinal artery in the neonatal period and to compare blood flow velocity of orbital vessels with that of the anterior cerebral artery and middle cerebral artery. METHODS: Forty-five healthy neonates (gestational age, 39.2 +/- 1.2 weeks; birth weight, 3,210 +/- 567 g) on the first and third postnatal days (90 eyes each time) and on the fifth day of life (34 eyes) were included in a clinical trial. A duplex scanner with mechanical sector probe was used for measuring blood flow velocity in the ophthalmic artery, central retinal artery, anterior cerebral artery, and middle cerebral artery. A nominal imaging frequency of 7.5 MHz, a transmitted Doppler frequency of 5 MHz, and a wall filter setting of 50 Hz were used in each case. Systolic, end-diastolic, and mean-enveloped velocities were measured for the studied vessels and the resistance and pulsatility indices were calculated. RESULTS: On the first postnatal day, blood flow velocities and indices in the ophthalmic artery were systolic 14 +/- 2.4 cm/sec, end-diastolic 3.8 +/- 0.6 cm/sec, mean-enveloped 7.3 +/- 1.3 cm/sec, resistance index 0.73 +/- 0.03, and pulsatility index 1.5 +/- 0.2. Central retinal artery blood flow velocities and indices were systolic 8.7 +/- 1.8 cm/sec, end-diastolic 2.7 +/- 0.7 cm/sec, mean-enveloped 5.0 +/- 1.1 cm/sec, resistance index 0.70 +/- 0.04, and pulsatility index 1.3 +/- 0.1. There were no significant differences in ophthalmic artery and central retinal artery flow velocities between right and left eyes. Doppler values of the central retinal artery were significantly lower (P = .0005) than those of the ophthalmic artery for each day studied. The Doppler data for the central retinal artery and ophthalmic artery were significantly lower (from P = .005 to .0001) than those observed in the anterior cerebral artery and middle cerebral artery at the same postnatal age. No significant differences in flow variables were found in the central retinal artery and ophthalmic artery from the first to third day, whereas blood flow velocities in the anterior cerebral artery and middle cerebral artery increased significantly (P = .01 to .0001) from day 1 to day 3. On the fifth day of life a significant increase in blood flow velocities and indices was observed in the ophthalmic artery, whereas only systolic velocity significantly increased in the central retinal artery. CONCLUSIONS: We report blood flow data of the ophthalmic artery and central retinal artery in healthy neonates and suggest that a delay of arterial blood flow changes occurs for the ophthalmic artery and central retinal artery with respect to the anterior cerebral artery and middle cerebral artery in the early prenatal period.

A three year follow up of preterm infants after moderately early treatment with dexamethasone.

OBJECTIVE: To assess the effect of moderately early postnatal dexamethasone treatment on growth and neurodevelopmental outcome in preterm infants. METHODS: Thirty preterm infants enrolled in a randomised clinical trial to investigate the effectiveness of moderately early dexamethasone administration in the treatment of chronic lung disease were routinely followed up. Fifteen babies received a total dose of 4.75 mg/kg over 14 days from the 10th day of life, and 15 babies were untreated. Five infants in each group received open label steroids to facilitate extubation later in their clinical course. Growth and neurodevelopmental outcome are reported. RESULTS: The mean body weight, height, and head circumference as well as the number of babies with anthropometric measurements within normal range were similar in treated and untreated babies. There was no significant difference between treated and control groups with respect to incidence of cerebral palsy, major neurosensory impairment, mean intelligence quotient scores, and behavioural abnormalities. CONCLUSIONS: Postnatal dexamethasone treatment with the schedule used in this study did not impair growth and neurodevelopmental outcome in preterm infants. Data from larger trials have raised major concern that postnatal steroid treatment may increase neurodevelopmental impairment. The full extent of the risk will only be known when more trials have reported follow up data.

Perceptual-motor, visual and cognitive ability in very low birthweight preschool children without neonatal ultrasound abnormalities.

Thirty-six children born preterm with very low birth weight without neonatal brain disorders and normal cerebral ultrasound findings were examined at pre-school age: visual, perceptual motor, attention, behaviour and cognitive assessments were performed in the study group as well as in a control group of term children matched for age, sex and parental educational and occupational status. The results showed a significant lower scoring in perceptual motor skills in the study group, associated with a defect of accuracy in spatial attention and a higher incidence of stereopsis impairment related with perceptual motor disabilities. Behavioural disorders, in terms of emotional maturation and hyperactivity, were significantly more frequent in the study group. To prevent behavioural and learning problems at school, a complete longitudinal assessment including visual functions and perceptual motor abilities seems mandatory in preterm born children, even in the absence of neonatal brain disorders including abnormal cerebral ultrasound findings.

Neonatal outcome of spontaneous and assisted twin pregnancies.

OBJECTIVES: Over the last 10 years, diffusion of assisted reproduction techniques (ovarian stimulation, IVF, GIFT) has led to an increased incidence of multiple pregnancies and consequently, of the related obstetric-neonatal problems. In this study, multiple births have been studied, with particular reference to the twin births occurring in the Gemelli hospital, Rome. The hospital is also a reference centre for obstetric pathologies and infertility treatment. In particular, attention has been focused on neonatal outcome, comparing twins born from spontaneous and assisted pregnancies. STUDY DESIGN: 228 neonates from spontaneous twin pregnancies and 32 from assisted twin pregnancies were taken into consideration with regard to: premature birth, low birth-weight, intrauterine growth retardation, weight discordance, Apgar score, major neonatal diseases, and mortality. RESULTS: Results showed a significant higher incidence of prematurity and low birth-weight, as well as a significant lower gestational age, occurring more frequently in twins resulting from assisted pregnancies than in twins from spontaneous pregnancies. Furthermore, the incidence of severe depression at birth and respiratory disease was significantly higher in twins from assisted pregnancies than in those from spontaneous pregnancies, despite similar gestational age and birth-weight.

Transient evoked otoacoustic emissions (TEOAEs) in new-borns: normative data.

OBJECTIVE: Early diagnosis and rehabilitation of congenital hearing loss are mandatory in order to achieve a satisfactory linguistic and cognitive development. A universal hearing screening in order to identify congenital hearing losses before 3 months of age is required. METHODS: TEOAEs are an easy to perform, short lasting, not invasive and low-cost test with a high sensitivity. 320 at term new-borns (640 ears) without any risk factor for hearing loss underwent TEOAEs. The new-borns were screened 3 days after birth. Those who failed the first test were retested when possible before the discharge from the hospital. ABR was performed 3 months later in cases who failed TEOAE. RESULTS: The median TEOAE sampling time was 98 s, the median test duration was 14 min. The mean stimulus amplitude was 80 dB peSPL in the left ear and 81 dB peSPL in the right ear, noise levels within the external meatus during sampling were 44 dB SPL on the right ear and 43 dB SPL on the left one, noise contained within the response (A-B difference) was 8.65 dB SPL in the left ear and 8.74 dB SPL in the right ear, mean TEOAEs amplitudes were 21.49 dB SPL and 21.78 dB SPL in the right and left ear respectively, the mean lower and upper limit of the spectrum being 678 and 5720 Hz. According to these criteria 494/640 ears (77.2%) passed the test at the first recording, while TEOAEs resulted to be absent in 146/640 ears (22.8%). A retest was performed successfully before the discharge from the Hospital in 30/640 ears (4.7%). An ABR recording within the third month of life was scheduled as out-patient in the 58 new-borns (116 ears, 18.2%) who failed the test. 18 of them (36 ears, 5.6%) did not complete the program, 19 new-borns (38 ears, 11.8%) showed a normal ABR, while two new-borns (four ears, 0.6%) failed ABR after 3 months. A second ABR performed after 6 months was normal. CONCLUSIONS: TEOAEs recording seems at now the test of choice for a universal hearing screening. However, a greater standardization of criteria both in performing the test and in evaluating the results is needed.

Molecular analysis of Klebsiella pneumoniae strains isolated in pediatric wards by ribotyping, pulsed field gel electrophoresis and antimicrobial susceptibilities.

The purpose of this study was to investigate the usefulness of different molecular typing techniques in the surveillance and control of the spread of extended-spectrum-beta-lactamase-(ESBL) producing Klebsiella pneumoniae in the pediatric department of the "Agostino Gemelli" hospital of the Catholic University in Rome, over a period of nine months. The strains were characterized by ribotyping using HindIII as restriction enzyme and pulsed field gel electrophoresis (PFGE) using XbaI as endonuclease. Sixty six K. pneumoniae clinical strains were isolated during this period, the first 32 were isolated in the summer of 1998. Among these first isolates, ribotyping generated 26 different patterns whereas PFGE produced 16 patterns. The remaining 34 strains were isolated during January and April 1999 and all of them were ESBL producers. Ribotyping clustered the strains into 6 patterns whereas PFGE generated only 3 patterns. PCR revealed the presence in 10 isolates of both bla(TEM) and bla(SHV) genes and 24 strains carried only the bla(SHV) gene. In our experience ribotyping revealed a higher power of differentiation with respect to PFGE and was of great help in the surveillance of the infection.

Normal neonatal values of ophthalmic and central retinal artery blood flow velocities.

PURPOSE: To define standard values of blood flow velocities and indices in the ophthalmic and central retinal arteries in the neonatal period. METHODS: Forty-two healthy full-term neonates comprised the study population. A color Doppler with mechanical sector probe was used for measuring blood flow velocity in the ophthalmic and central retinal arteries. Systolic, end diastolic, and mean-enveloped velocities were measured, and the resistance index and pulsatility index were calculated. RESULTS: Ophthalmic artery Doppler velocities were similar on the first and third days of life, but increased significantly on the fifth and seventh days of life; resistance index significantly increased during the first week of life, whereas pulsatility index did not change significantly. Doppler velocities of the central retinal artery were similar on the first and third days; they show a delayed increase compared to the ophthalmic artery. Central retinal artery blood flow velocities increased significantly from the third to seventh postnatal day. Resistance index also increased between the first two days and on the fifth and seventh postnatal days, while pulsatility index did not change. CONCLUSION: These data constitute a starting point for studying the possible relationship between eye circulation and pathogenesis of retinopathy of prematurity.

[Neonatal lupus: different clinical neonatal expression in siblings]. / Lupus néonatal: une fratrie de nouveau-nés avec différentes expressions cliniques.

Neonatal Lupus Syndrome is a rare disease caused by placental passage of maternal autoantibodies. Pathogenesis is partially unknown and many clinical manifestations are possible. We report on newborn siblings who presented with different symptoms of Neonatal Lupus Syndrome. One patient presented with congenital heart block and another with hepatic and haematologic involvement. Cases of Neonatal Lupus among siblings are very rare, because of the high risk of pregnancy in affected women. Various clinical expressions may be explained by a different specificity of Anti-Ro autoantibodies among siblings. The reported cases are commented with regard to recent literature, trying to explain their pathogenesis.

[Ineffectiveness of vitamin 25(OH)D3 in the prevention of hypocalcemia induced by phototherapy]. / Inefficacia della vitamina 25(OH)D3 nella prevenzione dell'ipocalcemia indotta dalla fototerapia.

Phototherapy causes a higher incidence of hypocalcemia in preterm infants by still unknown pathogenetic mechanism. The authors studied 100 preterm newborns in order to verify whether Calcifediolo (25-OH-D3) could be useful to prevent the phototherapy-induced hypocalcemia. Results obtained show that Calcifediolo is not able, anyway, to lower the increase of the phototherapy-induced hypocalcemia in preterm infants. Vit D is therefore unlikely to play any important role in the patogenesis of phototherapy-induced hypocalcemia.

[Assistance procedures in the perinatal period that condition breast feeding at the time of discharge from the hospital]. / Procedure assistenziali del periodo perinatale che condizionano l'allattamento al seno alla dimissione dall'ospedale.

The authors have evaluated the influence of some obstetric events (type and duration of labour and method of delivery) and some pharmacological factors (oxytocic drugs during labour, local infiltration, duration of general anaesthesia, oxytocic drugs and/or ergot derivatives during puerperium) on frequency of breast-feeding at the time of discharge from hospital. About 57% of 356 newborns were breast-fed (wholly or prevalently) at discharge from the "A. Gemelli" University Hospital in Rome, during two months period (march-april 1981). The results showed that all those conditions requiring medical and paramedical action, either instrumental or pharmacological (such as: induced labour, prolonged labour, operative delivery either vaginal or abdominal, particularly in emergency; use of local infiltration; use of oxytocic drugs during labour, particularly for induction; prolonged general anaesthesia in caesarean section) may have an unfavorable effect, nearly always significant, on breast-feeding. According with these results, the Authors suggest the following measures for breast-feeding promotional programme: modification of neonatal routine care to promote an earlier mother-infant interaction during lying-in; limitation of avoidable obstetric procedures and of drugs giving to mothers; a better understanding of pharmacokinetics, both in mothers (placentar passage of drugs and through milk) and in newborns during labour, delivery and puerperium.

[Which light for phototherapy of the low birth weight infant?]. / Quale luce per la fototerapia nel neonato di basso peso?

We have compared three different fluorescent light sources (true light, blue light, true light + blue light) for phototherapy in 155 low birth weight newborn babies affected with non haemolytic hyperbilirubinaemia. Our data suggest that blue light is significantly more effective than true light. Surprisingly the association of true light with blue light is significantly more effective than both true light and blue light separately. The greater effectiveness associated with the better tolerance of true light + blue light respect to blue light only, makes it preferable than phototherapy regimen, even if more extensive study on its effectiveness and on short and long term side effects are need.

[Parity and the quantity of suckled maternal milk produced in the 1st 4 days of the puerperium]. / Parità e quantità di latte materno da suzione prodotta nei primi quattro giorni del puerperio.

In 120 nursing mothers, the quantity of milk suckled was evaluated during the first days of the puerperium. Measurements of the milk intake were based on the difference between the weights of the neonate before and after each feeding. It was noted that, as the parity of the mother increased, the mean quantity of breast milk suckled/24 hours increased on the 1st, 2nd and 3rd day of the puerperium, as well as during the last 24 hours prior to discharge from the hospital (3rd or 4th post-partum day). Given the importance of a satisfactory flow of breast milk during the first days of the puerperium in the successful initiation of the breast-feeding experience, the authors would like to emphasize the increased risk of failure in the primipara and to suggest that greater attention be given to the effect of maternal parity in programs which promote breast-feeding.

[Effects on growth, tolerability and biochemical parameters of two different human milk fortifiers in very low birth-weight newborns]. / Effetti sull'accrescimento, sulla tollerabilitlà e sui parametri biochimici dell'uso di due tipi di fortificanti del latte materno in neonati di peso molto basso.

OBJECTIVES: The aim of the study was to compare a group of very low birth-weight infants feeded with a preterm formula with two other groups feeded with human milk and two different fortifiers. METHODS: 30 preterm newborns with birth-weight < 1.500 g, admitted to the Neonatal Intensive Care Unit (NICU) of Department of Neonatology of Catholic University of Rome were randomized for three different feeding groups: total enteral nutrition with HM fortified with Enfamil Human Milk fortifier or with Eoprotin, compared to a group feeded with Similac 24 preterm formula. Statistical analysis was performed using the two-way analysis of variance (ANOVA). RESULTS: During the study and at the end we found a growth rate for weight, cranial circumference and lenght similar to the fetal standard growth rate in the third trimester of pregnancy in all the three groups. Fortified HM was well tolerated. No pathologic value of the biochemical parameters studied was found. Higher level of serum phosphorus in spite of significantly lower intakes of phosphorus occurred in fortified HM feeded neonates, as if there was a better availability of this nutrient in HM. CONCLUSIONS: This study demonstrates the role of fortified HM as a good alternative to the preterm formula.

[Efficacy of phototherapy in the low weight newborn infant: relation to gestational age, birth weight and intra-uterine growth]. / L'efficacia della fototerapia nel neonato di basso peso: relazione con età gestazionale, peso neonatale ed accrescimento intrauterino.

Phototherapy is largely used in the management of neonatal hyperbilirubinaemia, but its safety is very far from being proved. The Authors studied the effectiveness of daylight in low-birth-weight newborns. The results obtained show that the reduction of bilirubin induced by phototherapy is related with gestational age and intra-uterine growth. The very low-birth-weight infants, at higher risk of kernicterus, as they are more responsives to phototherapy, as well they are, probably, more susceptibles to side-effects. The Authors think that phototherapy should be planned on the basis of such observations.

[Alimentary strategies in the neonatal period in the prevention of allergies]. / Strategie alimentari nella prevenzione dell'allergia in età neonatale.

The Authors report an update relative to the dietetic prevention strategies in the high allergic risk subject, as proposed from more recent literature. The babies with a familiar history of atopia are defined as population with allergic risk. The Authors examine the role of early exposure to cow's milk formulas and maternal diet during breast-feeding as risk factors for allergic symptoms in such babies. Moreover, they examine the indications for hydrolisated milk (partial and extensive) formulas and soy milk formulas use, as reported in published Meta-analysis and official statements of several Scientific Associations. They conclude that beyond the undoubted preventive role of exclusive breast-feeding in the first 4-6 month after birth, and of the extensively hydrolisated formulas, there are many concerns about the role for partially hydrolisated formulas and soy formulas. The Authors claim for multicentric methodologically correct trials in order to clear the controversies.