[Assessment of developmental outcome of preterm babies]. / Bébé prématuré, bébé particulier? Quel suivi développemental?

Increasing survival of very preterm and sick neonates has lead to more concern about development outcome. Risk factors include antenatal, perinatal and socioeconomic factors. Developmental assessment has to be repeated during infancy till late school age (at term 3, 6, 12, 18, 42 months corrected age ...). Neurological examination, sensorial assessment and cognitive evaluation with special attention to visuo-spatial factors are mandatory.

[Prematurity and infant-parent attachment disturbances. Assessment and intervention]. / Le prématuré confronté aux troubles de l'attachement parents-enfant. Prévention et prise en charge.

Premature birth is a factor of impaired infant-parent attachment. In addition it is frequently associated with other factors of impaired attachment related either to the infant (mainly the various pathologies of the premature infants and the hospitalization) and/or to the parents, specially the mother. The main characteristics of the normal process of infant-parent interaction are described as a basis for the early recognition and assessment of impaired interaction and preventive intervention.

Adaptation in neonatology of the once-daily concept of aminoglycoside administration: evaluation of a dosing chart for amikacin in an intensive care unit.

BACKGROUND: The bactericidal efficacy of aminoglycosides is directly related to peak serum concentration (Cmax), particularly the first one. Transitory high concentrations of aminoglycosides do not result in such a high drug uptake by renal and cochlear tissues because of the saturation of cell binding sites. These observations have led to the concept that less frequent administration of relatively larger doses of aminoglycosides would be of interest in treating infectious diseases. OBJECTIVE: Prospective evaluation of a dosing chart of amikacin (Ak) in high-risk neonates suspected of infection within the first 2 days of life. This dosing chart was based on a previous pharmacokinetic population study published elsewhere, treated accordingly to the new once-daily concept of aminoglycoside administration. STUDY DESIGN: One hundred and seventy-seven neonates (69 females and 108 males; mean gestational age (GA +/-SD: 33.6 +/- 4.1 weeks (W) received Ak regimen dosage according to the following dosing chart: Group (Gr) 1a GA <28 W: 20 mg/kg/42 h; Gr 1b GA 28 /= 37 W: 15.5 mg/kg/24 h. In case of asphyxia, hypoxic episode and intercourse treatment with indomethacin, the interval was systemically increased by 6 h whatever the GA groups. The mean duration time of Ak treatment (+/- 1 SD) was 5.00 +/- 2.01 days (range 2-13). Ak serum concentrations 1 h after completion of 30 min infusion (C1h), and successive Ak serum concentrations just before next administration depending on the difference of interval between each group (so defined minimum serum concentration (Cmin)), were determined in each neonate. Creatininemia during the fist postnatal weeks was used as an index of glomerular filtration rate; brainstem auditory evoked potentials (BEAPs) were used in 139 babies when reaching a postconceptional age of >/= 36 weeks to assess possible ototoxicity, and were compared to values from a group of term and a group of preterm babies, previously defined as our reference control groups. RESULTS: At day 1 of treatment, there was no correlation between the Ak C1hS and the GA at birth (mean 27.8 +/- 5.21 microgram/ml (+/- 1 SD); median 28; r = -0.003; range 10-40). In the same way, there was no correlation between the first Ak CminS and the GA at birth (mean 3.7 +/- 2.0 microgram/ml (+/- 1 SD); median 3.0; r = -0.33; range 0-10). The lack of correlation between these first observed C1hS and CminS and the GA at birth suggests the validity of our previous established dose regimen recommendations. Analyzing the data between groups, the mean value +/- 1 SD of Ak C1hS at day 1 of treatment was not significantly different (p > 0.05). Concerning the first Ak CminS, a significant difference (p < 0.01) was only observed when comparing groups 1a, 1b and 2 to group 4. However, this significant difference disappeared when comparing the successive next Ak CminS between groups while each interval remained the same, suggesting a positive postnatal maturation of the renal clearance. In the same way, creatininemia showed a significant and normal decrease (p < 0.01) in each group during the first postnatal weeks. Threshold values of BEAPs at 30 dB showed no significant difference (p > 0.05) between the treated groups (preterm group and term group) and the corresponding control groups. While the primary aim of the study was not to test the bactericidal efficacy of this new regimen, the recovery was excellent in 37 babies with proven or highly suspected infectious disease, except in 1 of them who died from septic shock (group B Streptococcus). After 5 years of using this kind of Ak administration in the unit, minimal inhibitory concentration profiles tested in 43 successive bacterial strains collected from inborn patients remained adequate. (ABSTRACT TRUNCATED)

High-frequency oscillatory ventilation in neonatal RDS: initial volume optimization and respiratory mechanics.

To determine whether initial lung volume optimization influences respiratory mechanics, which could indicate the achievement of optimal volume, we studied 17 premature infants with respiratory distress syndrome (RDS) assisted by high-frequency oscillatory ventilation. The continuous distending pressure (CDP) was increased stepwise from 6-8 cmH2O up to optimal CDP (OCDP), i.e., that allowing good oxygenation with the lowest inspired O2 fraction. Respiratory system compliance (Crs) and resistance were concomitantly measured. Mean OCDP was 16.5 +/- 1.2 cmH2O. Inspired O2 fraction could be reduced from an initial level of 0.73 +/- 0.17 to 0.33 +/- 0.07. However, Crs (0.45 +/- 0.14 ml . cmH2O-1 . kg-1 at starting CDP point) remained unchanged through lung volume optimization but appeared inversely related to OCDP. Similarly, respiratory system resistance was not affected. We conclude that there is a marked dissociation between oxygenation improvement and Crs profile during the initial phase of lung recruitment by early high-frequency oscillatory ventilation in infants with RDS. Thus optimal lung volume cannot be defined by serial Crs measurement. At the most, low initial Crs suggests that higher CDP will be needed.

The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome.

OBJECTIVE: To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support. DESIGN: A prospective randomized clinical trial. SETTING: Three community-based level III neonatal intensive care units. SUBJECTS: A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50. INTERVENTIONS: Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit. MEASUREMENTS AND MAIN RESULTS: No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants. CONCLUSIONS: When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost.

Once-a-day administration of amikacin in neonates: assessment of nephrotoxicity and ototoxicity.

Neonates, especially preterms, are known to have low glomerular filtration rates (GFR). This may result in elevated trough concentrations during multiple administration of aminoglycosides (AGs), potentially leading to nephro- and ototoxic reactions. The once-daily administration (q.d.) of AGs has been shown to be equally or better tolerated in adults and children than the conventional schedules (twice daily, b.i.d.; thrice daily, t.i.d.), while offering potential pharmacodynamic and nursing advantages. No data, however, are available for neonates. As a consequence, this pilot study was conducted in order to assess the tolerance of the once-a-day administration of amikacin in comparison with the twice daily dose regimen, in relation to the pharmacokinetics of the drug under these two schedules. 22 Male neonates (gestational age > or = 34 weeks; postnatal age < or = 2 days) were randomized to receive amikacin (AK) (15 mg/kg/day) q.d. (n = 10) or b.i.d. (n = 12) together with ampicillin (50 mg/kg/12 h). AK plasma levels were measured at days 1, 3, 5 and 7 of treatment just before the next dose (trough level) and 1 h after completion of infusion (peak level) and after 3 and 6 h only at day 1. Due to the small size of the samples, no difference in efficacy could be assessed and was not the aim per se. Glomerular dysfunction was assessed by creatinine clearance, and tubular injuries by the urinary excretion of proteins (retinol binding protein, beta 2-microglobulin, clara cell protein (P1) and microalbumin), enzymes (N-acetyl-beta-D-glucosaminidase, alkaline phosphatase, alanine aminopeptidase, and gamma-glutamyltransferase), and total phospholipids (TPL) in urine. Ototoxicity was assessed by brainstem auditory evoked potentials (BAEPs) at days 0, 3 and 9 of therapy. Eight healthy neonates served as controls. All patients showed a normal and similar increase of GFR during the first postnatal days. Proteinuria did not increase, but enzymuria and TPL increased significantly during the treatment in both AK groups without significant difference between groups. BAEPs at day 9 were not significantly different between treated and untreated patients. We conclude from this pilot study that, in the absence of more toxicity, the q.d. administration of AK in neonates of > or = 34 weeks of gestational age may be recommended over its bid schedule in view of its potential advantages.

Natural disaster situations and growth : A macroeconomic model for sudden disaster impacts

The aim of this paper is to examine the realtion between a natural disaster situation and its potencial effects on a growth rate of output, by means of a simple macroeconomic model, which is later applied as a demonstration to a sample of countries affected by major natural disasters in the last two decades. This quantitative application appears to support the model. The main conclusions are that capital loss is unlikely to have an important effect on growt and that a very moderate response expenditure may be sufficient to prevent the growth rate of output from falling. A general derived conclusion is that foreign and public disaster response may be better used to help actual victims and affected activities directly than to proceed on the rather unsound prima facie belief that the economy will be heavily affected by the disaster

Maillard reaction products and lysinoalanine: urinary excretion and the effects on kidney function of preterm infants fed heat-processed milk formula.

Heat processing is essential for the preservation of milk-based infant formulas. Heating, however, induces a number of chemical changes during which lysine in the milk proteins reacts with reducing sugars to form Maillard reaction products (MRPs) and also reacts with the dehydroalanine resulting from cystine degradation to form lysinoalanine (LAL). Both products have been reported to induce histological changes in the straight portion of the proximal tubule in the rat kidney. This pilot study was made to investigate the urinary excretion by healthy preterm babies of MRPs and LAL contained in infant formula and to determine their influence on kidney function. Twelve healthy male preterm babies were first fed for 10 days with pooled human milk and then for 5 days with each of two experimental premature infant formulas in a cross-over design. The infant formulas were sterilized either by ultra-high temperature (UHT) treatment or by a conventional retort process to give products with low and high levels of MRPs and LAL, respectively. In total, some 15.6% of the initial lysine had been modified in the in-can-sterilized product, compared to 6.2% in the UHT product. Urinary excretion of MRP lactulosyllysine ranged from 1.3 to 3.9% of the ingested amount, whereas that of LAL ranged from 6.2 to 9.3%. The higher level of MRPs and LAL in the formulas compared to breast milk had no influence on creatinine clearance or electrolyte excretion. There was no evidence of tubular damage as determined by the urinary excretion of four kidney-derived enzymes. Feeding of formula, however, did result in a general increase in urinary microprotein levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Phosphorus intake in preterm babies and variation of tubular reabsorption for phosphate per liter glomerular filtrate.

Inadequate low intake of phosphorus can induce a hypophosphatemic depletion syndrome resulting in hypercalcemia, hypercalciuria, hypophosphatemia, and rickets. Tubular reabsorption for phosphate per liter glomerular filtration rate (TP/GFR) has been proposed as a reliable index of renal phosphate handling for all age groups. In the present study, carried out in 12 healthy premature babies fed unmodified pooled human milk and then a preterm formula for two periods of 10 days, we demonstrated clearly that TP/GFR as well as calciuria can reflect the poor phosphorus intake and that the kidney of preterm babies is able to rapidly adapt itself to an increase in phosphorus diet content.

A scoring system in predicting the risk of intestinal stricture in necrotizing enterocolitis.

Of 46 infants with a diagnosis of necrotizing enterocolitis (NEC) admitted to the neonatal intensive care unit over the period 1981-1985, 40 have been followed from 2 to 6 years after the acute episode. A contrast enema (CE) to look for intestinal strictures (IS) was performed either during the first months in surgically managed patients, or between 2 and 6 years in asymptomatic patients. Clinical, laboratory and radiology parameters collected during the 7 days following NEC were used to establish a score which was correlated with radiological data obtained after CE. Of the 40 infants, 17 developed symptomatic or asymptomatic IS and 16 of these 17 infants has a score greater than or equal to 7. Nineteen of the 23 patients without IS had a score less than 7. We conclude that the proposed score established on day 8 after onset of NEC helps to identify infants at higher risk of developing IS and for whom closer follow up appears necessary.

Tracheal agenesis: an exceptional cause of neonatal respiratory distress.

The absence of the trachea is a rare and always lethal congenital malformation. Temporary survival depends on ventilation through the esophagus. We report our experience with a newborn who presented this unusual tracheal abnormality in association with cardiac malformation.

Exogenous prostaglandin administration and pseudo-Bartter syndrome.

Biological abnormalities simulating Bartter syndrome were observed in a preterm neonate with complex cyanotic congenital heart disease, for which ductus arteriosus was maintained open by high doses of prostaglandin (PG) until a Blalock shunt could be performed. These abnormalities spontaneously disappeared after cessation of PG administration. We postulate that the natriuretic effect of exogenous administered PG could further increase sodium wasting already induced by the cardiopathy thus leading to pseudo-Bartter syndrome.

Validity of N-acetyl-beta-D-glucosaminidase (NAG) determination in assessing netilmicin nephrotoxicity in preterm babies.

The supposed nephrotoxicity of netilmicin has been assessed in preterm neonates using the urinary excretion of a lysosomal enzyme as marker: N-acetyl-beta-D-glucosaminidase (NAG). 17 male preterm neonates with birth weight appropriate for gestational age were enrolled in a study where 9 received netilmicin therapy since the first day of life and 8 served as control group. We observed a significant increase in urinary NAG/creatinine ratio during the postnatal days in the netilmicin group babies followed by a regular decrease during the days after the end of therapy. If this increase in lysosomal enzymuria such as NAG could reflect netilmicin nephrotoxicity on the proximal tubular cell, many questions remain unanswered about the exact significance of this finding. In particular, its relation with tubular cell dysfunction remains to be established.

Aminoglycoside nephrotoxicity and urinary excretion of N-acetyl-beta-D-glucosaminidase.

The purpose of this paper is to discuss briefly the mechanism of aminoglycosides nephrotoxicity. This kind of antibiotic seems to act preferentially on the phospholipid metabolism of the proximal tubular cell. A lysosomal enzyme, N-acetyl-beta-D-glucosaminidase, could be of interest in assessing this renal interference.

Normal values for urinary N-acetyl-beta-glucosaminidase excretion in preterm and term babies.

Urinary N-acetyl-beta-glucosaminidase (NAG) excretion was measured in 14 healthy, preterm, male neonates with gestational ages between 32 and 35 weeks. Daily NAG excretion increased significantly during the first four weeks of life. No correlation was observed between urinary NAG:creatinine ratio and postnatal age regardless of whether measurements were taken from the whole 24 hour urine collection or from an isolated urine spot sample at the same time on each day. When the preterm infants were compared with a group of 20 healthy, full term, male infants at a postnatal age of 7 days the NAG:creatinine ratio was significantly higher in the preterm group, the measurements having been taken from single urine spot samples. We suggest that this variable be used in the evaluation of renal tubular integrity during the neonatal period.