[Pharmacologic treatment of neonatal jaundice. A new approach]. / Traitement pharmacologique de l'ictère du nouveau-né. Un nouvel essor.

Pharmacological treatment of neonatal jaundice is again topical. At the beginning of the eighties, clofibrate was added to phenobarbital which was difficult to use and inefficient. Clofibrate is a better enhancer of glucuronosyl transferase induction than phenobarbital and causes 100% increase of hepatic bilirubin clearance within 6 hours. In the treatment of early jaundice in full term neonate, it significantly reduces bilirubinemia in 16 hours, and decreases the intensity and duration of jaundice and also phototherapy requirement. At the end of the eighties, new molecules inhibiting hepatic production of heme to bilirubin, like metalloporphyrins, were introduced. These molecules block the transformation of heme to biliverdin and bilirubin. Among them, the Sn-mesoporphyrin seems to have the best efficacy when used prophylactically in premature infants between 30 and 36 weeks of gestational age, and also curatively in full-term neonates, with minimal side effects. However the product is not yet manufactured and can not be used in pediatrics practice. Therefore clofibrate represents the only pharmacological treatment of neonatal jaundice actually available.

Are neonatal brain lesions due to intrauterine infection related to mode of delivery?

Studies of antenatal and intrapartum factors involved in the development of cerebral palsy have identified intrauterine infection and chorioamnionitis as high risk situations for white matter damage, especially periventricular leukomalacia. To characterise adverse or protective perinatal factors further, we undertook a multiple regression analysis of selected perinatal events in a population of 110 inborn premature neonates with documented chorioamnionitis. In the total population of 110 infants delivered at between 25 and 32 weeks, 101 (92%) survived the first week of life and two were subsequently excluded. Of the 99 remaining infants, 20 (20%) developed periventricular leukomalacia including 16 (80%) cystic lesions. Forty-five (45%) babies were born by lower segment caesarean section, and for 37 of these, this was carried out before labour. Fetal presentation at delivery was breech in 14 (26%) of those born vaginally and 23 (52%) of those born by lower segment caesarean section (OR 3 [95% CI 1.3-7]). Among predetermined perinatal risk factors for periventricular leukomalacia, logistic regression analysis showed that delivery by caesarean section was associated with a dramatic decrease in the incidence of periventricular leukomalacia (OR 0.15 [95% CI 0.04-0.57]). These preliminary results warrant confirmation and preferably a prospective study before considering caesarean section as a protective perinatal factor of periventricular leukomalacia.

Periventricular leukomalacia: risk factors revisited.

The dramatic improvement in neonatal care during the last decade did not succeed in reducing the incidence of periventricular leukomalacia (PVL), suggesting that prenatal events may be the main target for PVL prevention. The studied cohort included 753 very preterm infants born between 24 and 32 weeks of gestational age, admitted to the intensive care unit and surviving at least 7 days; 69 (9.2%) of these infants had a diagnosis of cystic PVL. The highest PVL frequency was observed among the infants born at 28 weeks of gestation (16%). Inflammatory prenatal events occurring during the last days or weeks before delivery and PVL occurrence are strongly correlated. Indeed, the combination of intra-uterine infection and premature rupture of membranes is associated with a very high risk (22%). Prolongation of pregnancy with tocolysis for more than 24 hours also carries a significant 8% risk of PVL. In contrast, chronic fetal distress of long duration, such as severe intra-uterine growth retardation and pre-eclampsia, is seldom followed by PVL (< 2% risk). Similarly, rapid unexpected deliveries entail a minimal PVL risk (4%). Experimental and epidemiological confirmations of these data would have an influence on the management of both the preterm onset of labour and the premature rupture of membranes.

[Sleeping position, prevention of sudden death syndrome and gastroesophageal reflux]. / Position de sommeil, prévention de la mort subite du nourrisson et reflux gastrooesophagien.

Based on results of epidemiological studies, dorsal or lateral sleeping positions are now recommanded in the prevention of sudden infant death syndrome (SIDS). This raises an ethical question about the attitude towards the ventral positioning therapy for gastroesophageal reflux (GOR). The consensus conference considers that the ventral position should only be recommanded in GOR when the benefit appears to outweigh the risk of SIDS that it induces. The conference proposes that for infants with simple uncomplicated reflux, sleeping in the prone position should not be introduced in the first line treatment. Prone positioning should be restricted to complicated cases resistant to dietary and medical measures.

[Pharmacokinetics of clofibrate in jaundiced newborn infants at term]. / Pharmacocinétique du clofibrate chez le nouveau-né à terme ictérique.

BACKGROUND: Clofibrate (CFB) has been proposed to increase elimination of bilirubin in neonates with hyperbilirubinemia. Nevertheless, its disposition, at this age, remains unknown. The aim of this work was to characterize pharmacokinetics of an oil formulation of CFB in neonates at term with jaundice. PATIENTS AND METHODS: Two groups (G1 and G2) of eight neonates, presenting with jaundice, entered an open, non randomized and comparative study. Five blood samples were collected over 50 hours following a single oral administration of 100 mg/kg or 50 mg/kg CFB, respectively, in G1 and G2. Serum concentrations of both CFB and clofibric acid (CFA) were measured by HPLC and the pharmacokinetic analysis was made by a non-compartmental method. Data were compared to those obtained in adults receiving 2 g dose of CFB. RESULTS: Tolerance to the treatment was excellent. Pharmacokinetic profiles were similar in both groups of infants. There was a slow and prolonged formation of CFA whose serum concentrations remained high 50 hours after drug administration. Non-hydrolyzed CFB was found in the blood of three neonates. Elimination of CFA was prolonged corresponding to a terminal half-life (t1/2m) often above 100 hours and sometimes incalculable. MRTo-->50 (h) was similar in both groups (ie 26.2 +/- 2.0 vs 25.5 +/- 1.3, respectively). The decrease of t1/2m was related to the decrease of the clearance of CFA. CONCLUSIONS: The decrease in CFB's metabolism in newborns is probably the result of at least two concurrent phenomenons: partial hydrolysis of CFA, especially at high doses, and decrease in the hepatic capacity to conjugate the active metabolite. A single oral administration of 50 mg/kg CFB seems to be a suitable schedule.

Periventricular leukomalacia: correlation between MR imaging and autopsy findings during the first 2 months of life.

PURPOSE: To correlate magnetic resonance (MR) imaging and pathologic findings in premature infants with periventricular leukomalacia (PVL). MATERIALS AND METHODS: Eight premature infants with PVL who died after 3-7 weeks of life were studied with in vivo T1-weighted MR imaging, and imaging patterns were compared with hypoxic-ischemic injuries at pathologic analysis. RESULTS: Cavities were seen as zones of absent or weak signal intensity. Translucent sparsely cellular zones appeared as areas of intermediate intensity, and cellular reactions were seen as limited linear or punctate zones of increased intensity, usually less intense than the cortex. MR imaging provided reliable depiction of these lesions, with adequate estimation of their volume and topography. However, the extent of periventricular cellular lesions was underestimated. In one case, blood seen as hyperintense or isointense zones masked portions of cystic lesions, and in three cases small thalamic lesions were overlooked. CONCLUSION: With the above limitations, T1-weighted MR imaging offers precise evaluation of PVL.

[Periventricular leukomalacia of late onset in a premature infant]. / Leucomalacie périventriculaire d'apparition tardive chez un prématuré.

BACKGROUND: Periventricular leukomalacia in preterm neonates is usually due to abnormal cerebral blood flow before and/or during delivery. It is diagnosed during the first month of life. This study describes a case of late-developing periventricular leukomalacia. CASE REPORT: A girl was delivered by cesarean section at the 23rd week of gestation that was complicated by placenta previa. She weighted 880 g and immediately required resuscitation. She did not develop respiratory distress syndrome. She was intubated and ventilated for the first two weeks of life and developed bronchopulmonary dysplasia requiring corticosteroid treatment. Extubation was possible on day 43. The neonate had been given antibiotics for the first 10 days of life and indomethacin on day 8 because of a patent ductus arteriosus. Repeated craniosonography showed moderate bilateral intraventricular hemorrhage and occipital areas of hyperechogenicity that disappeared at the end of the first month of life. Repeated electroencephalograms revealed no positive rolandic sharp waves until the infant was 42 days old. Craniosonography on day 48 showed areas of heterogeneous hyperechogenicity and NMR imaging showed bilateral frontoparietal leukomalacia with loss of white matter. The baby died on day 71. CONCLUSIONS: Late periventricular leukomalacia is exceptional and usually seen after postnatal abnormalities in cerebral blood flow and/or prolonged hypoxemia. Both these risk factors were absent in this patient.

Intravenous immunoglobulin therapy for prevention of infection in high-risk premature infants: report of a multicenter, double-blind study.

The effectiveness of intravenously administered immunoglobulin (Ig) therapy for prophylaxis of infection was evaluated in high-risk preterm infants. Two hundred thirty-five premature newborns were randomly assigned, in a double-blind controlled trial, to treatment and placebo groups. Thirty-five infants (29%) of the Ig group and 29 (25%) of the placebo group had one or more episodes of certain infection. Thirty infants (25%) of the Ig group and 18 (16%) of the placebo group had one or more episodes of probable infection. No significant differences were observed in the incidence of certain or probable infection in treated and control infants. Nevertheless, among the infants who had one or more certain or probable episodes of infection, more of them belonged to the Ig group than to the placebo group. The possible deleterious effect of the administration of large amounts of polyspecific Ig is discussed.

[Pre-eclampsia: a cause of fetal heart failure?]. / La toxémie gravidique: une cause d'insuffisance cardiaque foetale?

The authors report the case of a newborn whose mother presented with pre-eclampsia. Intrauterine growth retardation, peripheral edema, ascitis and pleural effusion were present at birth. The authors suggest that placental vascular abnormalities could be responsible for fetal heart failure and edema syndrome.

[Comparison of arterial and transcutaneous oxygen partial pressure in infants with bronchopulmonary dysplasia]. / Comparaison des pressions partielles artérielle et transcutanée en oxygène chez des nourrissons atteints de dysplasie bronchopulmonaire.

Transcutaneous PO2 (PTCO2) (Radiometer electrode heated to 44 degrees C) was compared to arterial PO2 (PaO2) in 19 infants with bronchopulmonary dysplasia: 12 infants were tested once, at the mean postnatal age of 14 weeks (range 4-43 weeks), the other 7 infants were studied longitudinally from 5 weeks (range 2-8 weeks) to 12 weeks (range 6-18 weeks) of postnatal age. The protocol was standardized: measurement during behavioral stage 1, using a peripheral arterial line. Twenty-eight comparisons between PTCO2 and PaO2 were obtained. PTCO2 was significantly related to PaO2 [PTCO2 (mmHg) = 0.81 PaO2 + 5.2, r = 0.73, p less than 0.01]. The mean difference PTCO2 - PaO2 was -7.2 mmHg (range: -34.5 to + 33); in the studied age range the PTCO2 - PaO2 was not significantly related to postnatal age (r = -0.24; p greater than 0.1).

[Intravenous-intramuscular bioequivalency of ceftriaxone in newborn infants]. / Etude de la bioéquivalence intraveineuse-intramusculaire de la ceftriaxone chez le nouveau-né.

In 6 neonates over 7 days of life, comparison of maximum and residual serum concentrations of ceftriaxone after intra-venous or intra-muscular administration showed the bio-equivalence of both ways. In both cases a single daily injection obtained bacterial serum levels on most of the strains responsible for secondary bacterial infections in neonates.

[Post-transfusion hemolysis in premature infants. Apropos of 8 cases of post-transfusion hemolysis in premature infants]. / Hémolyse transfusionnelle du prématuré. A propos de 8 cas d'hémolyse post-transfusionnelle chez des prématurés.

Accidents related to blood transfusion have become rare in neonates, due to the application of very strict rules. The 8 reported cases of post-transfusion hemolysis occurred in prematures less than 32 weeks gestational age. Signs consisted of hemoglobinuria and/or severe jaundice. In some patients exchange-transfusion had to be performed. Immuno-hematologic, bacteriologic and technical investigations did not show the etiology of these accidents. No similar clinical reports were found in the literature. Some authors suggest a mechanical origin.

[Maternal administration of indomethacin and neonatal tricuspid insufficiency]. / Administration maternelle d'indométacine et insuffisance tricuspide néonatale.

The authors report the case of a neonate who presented since birth with refractory hypoxemia, peripheral edemas, ascites and pleural effusions. The mother had been given indomethacin for the 10 preceding days, in order to avoid premature labour. Echocardiography showed a tricuspid valve dysfunction with important regurgitation in the neonate. Under symptomatic treatment, clinical symptoms disappeared within 10 days. Echocardiography was normal by age 3 months. The responsibility of administration of indomethacin to the mother is discussed.

[Comparison between the number and nature of fecal clostridia and other risk factors implicated in the intestinal pathology of newborn infants]. / Comparaison entre le nombre et la nature des Clostridium fécaux et d'autres facteurs de risque impliqués dans la pathologie intestinale des nouveau-nés.

One-hundred and fifteen infants aged 1 to 31 days from two intensive-care units were grouped into 6 classes according to clinical criteria (enterocolitis with or without anatomopathological examination and pneumatosis intestinalis, "haemorrhagic colitis", acute diarrhoea or absence of intestinal disorders). The total number of viable bacteria, the number of Clostridium and, in some cases, the presence of rota- and/or coronavirus were determined in their stools. The incidence of Clostridium in the stools of infants with enterocolitis (with or without pneumatosis intestinalis) or haemorrhagic colitis was not significantly different from that of infants without intestinal disorders, whereas stools of infants with acute diarrhoea less often contained Clostridium than those of other infants. C. butyricum, C. difficile, C. perfringens, C. tertium, and C. sordellii were identified. Correspondence analysis comparing the variable, "clinical profile", with 23 other variables, suggested that the variables of gemellity, a birthweight below 1900 g, a gestational age of less than 35 weeks, respiratory distress, umbilical catheterization and a Clostridium count above 10(7)/g at the onset of clinical signs, i.e. between 8 to 12 days of age, were linked to the clinical profile of necrotizing enterocolitis with pneumatosis intestinalis. Conversely, the absence of gemellity, a high birthweight and gestational age, the absence of respiratory distress or umbilical catheterization, the onset of diarrhoea within 8 days, and the presence of rota- and/or coronavirus in the stools were linked with a clinical profile of acute diarrhoea.