Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates.

AIM: Protein hydrolysates have been introduced in preterm formulae, but it is not clear whether they are needed for the feeding of preterm infants. We designed a randomized, controlled trial to test the effects of a preterm formula with hydrolysed cow's milk proteins on short-term growth and urinary and plasma amino acids levels. METHODS: Infants with a birthweight < or = 1750 g and gestational age < or = 34 wk fed a conventional preterm infant formula (formula B) or a hydrolysed formula (formula A). Weight was measured daily; length, head circumference, mid-arm circumference and total skinfold thickness were measured weekly. Blood and urine were analysed for amino acid concentrations at start, 14 and 28 d. RESULTS: Twenty-one infants met the criteria for randomization. The daily feeding volumes were: formula A 172.8 +/- 5.6 vs formula B 170.1 +/- 2.8 ml/kg/d. Infants fed with formula A showed slower weight gain (17.4 +/- 3.4 vs 20.5 +/- 3.3 g/kg/d; p = 0.045) and lower mean change in Z-scores for weight (-0.18 +/- 0.16 vs 0.00 +/- 0.09; p = 0.009) and for head circumference (-0.06 +/- 0.13 vs 0.06 +/- 0.13; p = 0.049). After 14 d, infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula B. CONCLUSION: Our results support the hypothesis of less nutritional value of hydrolysed versus conventional preterm formulae. Higher renal excretion of essential amino acids may be one of the mechanisms involved. These findings must be confirmed by further studies with larger sample sizes and protein hydrolysates with different degrees of hydrolysis.

[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.

[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.

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.

Adrenocortical function and chronic lung disease of pre-maturity: an unresolved problem?

The aim of this study was to investigate the relationship between adrenocortical function and chronic lung disease (CLD) of pre-term infants. Plasma F and ACTH were measured at 7, 14, 21 and 28 days of life in 25 pre-term infants with gestational age < or = 32 weeks and birth weight < or = 1,250 g. Fourteen infants developed CLD (CLD group) and 11 recovered without CLD (NOCLD group). Response to ACTH stimulation was tested on days 7 and 28. The results show that at the 7th day of life plasma F and ACTH levels were similar in the NOCLD and CLD group. CLD group had significantly higher plasma F and ACTH concentrations at the 14th (p=0.006 for F and p=0.020 for ACTH) and at the 21st (p=0.008 for F and p=0.024 for ACTH) day of life, while no significant differences were detected at the 28th day of life. The response to ACTH stimulation test was similar between the NOCLD and CLD group. These data demonstrate the lack of any significant association between adrenal insufficiency and CLD and discourage the use of baseline or stimulated plasma F levels to predict the development of CLD in pre-term infants.

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.

[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.

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.

Plasma levels of interleukin-6 and interleukin-10 in preterm neonates evaluated for sepsis.

UNLABELLED: In a prospective study, plasma interleukin-6 (IL-6) and interleukin-10 (IL-10) levels were measured by enzyme-linked immunosorbent assay in 45 premature neonates (25-34 weeks gestational age) with signs and symptoms of suspected sepsis at 0, 12 and 24 h; C-reactive protein (CRP) was measured at 0-24 h after enrolment. Six subjects were excluded due to insufficient blood sampling. The remaining 39 neonates were assigned to one of three groups: 25 newborns with sepsis (blood culture positive), seven with pneumonia (positive results on broncho-alveolar lavage fluid culture and characteristic chest radiography) and seven with necrotising enterocolitis (NEC) (characteristic intestinal and radiological signs according to the criteria of Bell et al.). A group of 20 healthy preterm neonates represented control subjects. On admission, higher levels of IL-6, IL-10 and CRP were observed in neonates with sepsis: IL-6 (median 1500 pg/ml, range 487-10000 pg/ml), IL-10 (median 113 pg/ml, range 70-196 pg/ml), CRP (median 22 mg/l, range 4-80 mg/l); pneumonia: IL-6 (median 1500 pg/ml, range 747-8000 pg/ml, IL-10 (median 84 pg/ml, range 76-92 pg/ml), CRP (median 10 mg/l, range 8-33 mg/l) and NEC: IL-6 (median 6650 pg/ml, range 1595-7950 pg/ml), IL-10 (median 80 pg/ml, range 61-147 pg/ml), CRP (median 3 mg/l, range 2.8-8 mg/l) as compared to controls (IL-6 median 208 pg/ml, range 198-349 pg/ml; IL-10 median 36 pg/ml, range 19-50 pg/ml; CRP median < 2 mg/l) (P < 0.05). In neonates with sepsis, IL-6 levels were significantly correlated with IL-10 levels (r = 0.65; P = 0.04) at the time of the second sample. The highest IL-6 levels were observed at onset, while IL-10 was predominant 12 h later. On admission, IL-10 and CRP levels were significantly higher in non-survivors (IL-10 median 507 pg/ml, range 422-753 pg/ml; CRP median 123 mg/l, range 20-219 mg/l) than in survivors (IL-10 median 76 pg/ml, range 61-143 pg/ml; CRP median 8 mg/l range 3-46 mg/l), while IL-10 levels were significantly higher (P < 0.05) also 12 h after admission (non-survivors: IL-10 median 600 pg/ml, range 538-800 pg/ml; survivors: IL-10 median 74 pg/ml, range 53-161 pg/ml). IL-6 and IL-10 levels were significantly correlated with CRP levels on admission (r = 0.45; P = 0.05). CONCLUSION: Preterm neonates with sepsis, pneumonia or necrotising enterocolitis showed increased interleukin-6, interleukin-10 and C-reactive protein levels. High interleukin-10 concentration was associated with mortality and could be an early indicator of prognosis.

Left ventricle dimensions in preterm infants during the first month of life.

This study was designed to evaluate left ventricle dimensions in preterm infants during the first month of life, in order to define reference values and their correlation with gestational age, birth weight, gender and baseline. Thirty-five infants, gestational age 25-29 (mean 27.9 +/- 1.4) weeks, birth weight 750-1249 (mean 965 +/- 206) g, were measured using echocardiography on days 3, 7, 14, 21 and 28 of life. The following dimensions were measured: end-systolic and end-diastolic interventricular septum thickness, end-systolic and end-diastolic left ventricle posterior wall thickness, end-diastolic and end-systolic left ventricle diameter. A progressive and significant increase of all the left ventricle measurements was observed during the first month of life. Left ventricle dimensions at the first scan (Day 3) correlated with birth weight but not with gestational age and gender. The degree of the increase observed during the first month of life was inversely related to the baseline, suggesting that the smaller the left ventricle is at birth, the higher is its postnatal increase toward dimensions similar to those of term infants. Our study gives reference data about left ventricle dimensions of preterm infants during the first month of life and is helpful when making a diagnosis of left ventricular hypertrophy in these subjects.

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.

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.

Caudal blockade as alternative therapeutic approach in neonatal arterial thrombosis.

Considering the high frequency of bleeding complications following fibrinolytic treatment, caudal blockade could be used in association with lower doses of tissue plasminogen activator as a possible new therapeutic approach in management of arterial thrombosis in neonates.

Transient effect of granulocyte colony-stimulating factor in allo-immune neonatal neutropenia.

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration at 10 microg/kg/day for 15-30 min over 3 consecutive days in 3 preterm neonates with allo-immune neonatal neutropenia (ANN) is reported. Patients 1 and 2 had antibodies against antigen NA2, while patient 3 had antibodies against NA1. All neonates developed a rapid increase in absolute neutrophil count which reached the normal range within 48 h (from 75-640/mm(3) to 2,520-4,700/mm(3)). However, 23-25 days later, all 3 neonates relapsed into a second phase of severe neutropenia (408-870/mm(3)). Antibodies against neutrophil antigens were still positive during this period. This second-phase neutropenia persisted for 20-30 days and resolved spontaneously. It may be possible that when rhG-CSF is administered within a short time after birth in neonates with ANN, its effect is exhausted before the concentration of circulating antibodies decreases, with the result that a second phase of neutropenia can be expected.

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.

Periodic lateralized epileptiform discharges (PLEDs) as early indicator of stroke in full-term newborns.

We report on periodic lateralized epileptiform discharges (PLEDs) on EEG in two infants with neonatal convulsions. In both neonates, the EEG abnormalities were seen soon after the onset of seizures, at a time when cranial ultrasound scans were thought to be normal. Subsequent Magnetic Resonance Imaging scans demonstrated cerebral infarction in both patients. In one case, the localisation of the lesion on MRI was concordant with that of the EEG abnormalities, as usually observed in adults with focal lesions. The other infant showed similar EEG abnormalities, but her MRI showed a localised lesion in the basal ganglia, which has also been reported to be involved in the genesis of these abnormalities.

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.

Prophylactic ibuprofen therapy of patent ductus arteriosus in preterm infants.

UNLABELLED: This study was aimed at evaluating the efficacy of ibuprofen in the prophylaxis of patent ductus arteriosus (PDA) in very preterm neonates and at detecting eventual side-effects. A total of 46 preterm neonates with gestational age under 31 weeks were randomly assigned at 2 h of life: 23 to the prophylaxis group and 23 to the control group. The prophylaxis group received intravenous treatment with ibuprofen lysine (10 mg/kg), followed by 5 mg/kg after 24 h and 48 h. No placebo was given to the control group. No PDA was demonstrated at 72 h of life in 20 of the 23 babies in the ibuprofen group (87%) nor in 7 of the 23 control neonates (30.4%). All neonates with PDA received treatment with indomethacin. One neonate in the prophylaxis group and three in the control group underwent surgical ligation. Prophylaxis with ibuprofen was not associated with any significant side-effect except for food intolerance. CONCLUSION: Ibuprofen prophylaxis seems to be efficient in closing patent ductus arteriosus and in reducing indomethacin treatment. No significant early side-effects were found due to ibuprofen.

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.

Efficacy of oral iodide therapy on neonatal hyperthyroidism caused by maternal Graves' disease.

OBJECTIVE: To verify the efficacy of oral iodide therapy in treating a case of early neonatal hyperthyroidism due to maternal Graves' disease. METHODS: We report a case of neonatal hyperthyroidism which occurred in a 2,650-gram, female baby, born at 39 weeks' gestational age (GA) to a 30-year-old mother affected by Graves' disease and treated with thionamides (propylthiouracil) from the 20th week of gestation. A fetal goiter, due to maternal therapy, had been observed by ultrasound scan at 31 and 35 weeks of gestation, with contemporary low cord thyroid hormone levels. Two intra-amniotic injections of levothyroxine were then performed at 34 and 36 weeks of gestation, which led to a significant reduction of fetal goiter and to normalization of cord thyroid hormone levels. The neonatal clinical course was characterized by symptoms of hyperthyroidism from the 2nd to 3rd days of life (irritability, tachycardia, tachypnea, hyperphagia), mostly during feeding. Oral treatment with potassium iodide (KI, 8 mg x 3 times a day) was started at 23 days of life. RESULTS: Treatment with KI led to a significant reduction of neonatal clinical symptoms and to a normalization of hormone levels within 4 days of therapy. The treatment was discontinued in 13th week of life because of neonatal well-being and normal hormone levels. CONCLUSIONS: We believe that KI therapy is effective in treating neonatal hyperthyroidism and does not cause suppression of neonatal thyroid activity, which is possible using antithyroid drugs like thionamides.