Abstract: A method is described whereby the concentrations and 2H isotope enrichment of glutathione (GSH) and cysteine can be simultaneously determined in a single gas chromatography-mass spectrometry run following derivatization as their N,S-ethoxycarbonyl methyl esters. Improvements of the derivatization protocol and the use of a short gas chromatography column combined with single-ion monitoring allow for rapid quantification of these parameters with acceptable precision and reproducibility (coefficient of variation less than 5%). The method makes possible their quantitative measurement in very small volumes (50 microL) of human umbilical cord blood, and is thus suitable for determining the cysteine and GSH concentrations and 2H isotope enrichments in blood samples from neonates or in other conditions in which sample size is restricted. It is shown that the fractional synthesis rate of human umbilical erythrocyte lysates in vitro is several-fold greater than that measured in vivo.

Abstract: BACKGROUND: The increasing survival rates of children who are born very preterm raise issues about the risks of neurological disabilities and cognitive dysfunction. We aimed to investigate neurodevelopmental outcome and use of special health care at 5 years of age in a population-based cohort of very preterm children. METHODS: We included all 2901 livebirths between 22 and 32 completed weeks of gestation from nine regions in France in Jan 1-Dec 31, 1997, and a reference group of 667 children from the same regions born at 39-40 weeks of gestation. At 5 years of age, children had a medical examination and a cognitive assessment with the Kaufman assessment battery for children (K-ABC), with scores on the mental processing composite (MPC) scale recorded. Data for health-care use were collected from parents. Severe disability was defined as non-ambulatory cerebral palsy, MPC score less than 55, or severe visual or hearing deficiency; moderate deficiency as cerebral palsy walking with aid or MPC score of 55-69; and minor disability as cerebral palsy walking without aid, MPC score of 70-84, or visual deficit (<3/10 for one eye). FINDINGS: In total, 1817 (77%) of the 2357 surviving children born very preterm had a medical assessment at 5 years and 396 (60%) of 664 in the reference group. Cerebral palsy was diagnosed in 159 (9%) of children born very preterm. Scores for MPC were available for 1534 children born very preterm: 503 (32%) had an MPC score less than 85 and 182 (12%) had an MPC score less than 70. Of the 320 children in the reference group, the corresponding values were 37 (12%) and 11 (3%), respectively. In the very preterm group, 83 (5%) had severe disability, 155 (9%) moderate disability, and 398 (25%) minor disability. Disability was highest in children born at 24-28 completed weeks of gestation (195 children [49%]), but the absolute number of children with disabilities was higher for children born at 29-32 weeks (441 children [36%]). Special health-care resources were used by 188 (42%) of children born at 24-28 weeks and 424 (31%) born at 29-32 weeks, compared with only 63 (16%) of those born at 39-40 weeks. INTERPRETATION: In children who are born very preterm, cognitive and neuromotor impairments at 5 years of age increase with decreasing gestational age. Many of these children need a high level of specialised care. Prevention of the learning disabilities associated with cognitive deficiencies in this group is an important goal for modern perinatal care for children who are born very preterm and for their families.

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Abstract: OBJECTIVE: Premature preterm rupture of membranes (PPROM) accounts for a significant part of overall perinatal mortality and morbidity. This study aims to define potential prognostic factors for neonatal outcome. PATIENTS AND METHODS: One hundred and thirty-one pregnancies complicated with PPROM at between 26 and 32 weeks were retrospectively reviewed over a three-year period. The influence of chorioamnionitis on perinatal morbidity and mortality was assessed using a composite outcome. RESULTS: On admission, gestational age (GA) at diagnosis, fetal heart rate anomalies and increasing severity of clinical features of chorioamnionitis were significantly related with an adverse outcome. Significant factors associated with a favourable outcome were an administration of steroids for lung maturation, prophylactic antibiotics and tocolytic therapies. Stratifying according to GA at PPROM, the survival rates were 43 and 52% at before 22 weeks and between 22 and 26 weeks respectively. The prognosis dramatically improved after 26 weeks with an 84.6% rate of survival without impairment. Although this rate reached 97.5% after 30 weeks, there was no statistical evidence supporting any benefit to prolong pregnancies beyond this point. The complete expression of chorioamnionitis independently increased the mortality rate by 41% (OR=1.41; 95% CI [0.99-2.01]. Overall, the most relevant factor was GA at delivery, levelling the prognostic value of GA at diagnosis. DISCUSSION AND CONCLUSION: If no consensus rules PPROM at the moment, the most efficient prognosis factor before 34 weeks is mostly determined by GA at delivery.

Abstract: OBJECTIVE: To assess the impact of antenatal corticosteroids (ACS) on neonatal mortality, cerebral lesions and 5-year neurodevelopmental outcome of infants born at 24-27 and 28-32 weeks of gestational age (GA). DESIGN: Observational population-based study including all births at GAs between 22 and 32 weeks in 1997 in nine regions of France. Survivors were assessed at the age of 5 years. SAMPLE AND METHODS: The population enrolled in the follow up comprised 2323 infants; there were 23 deaths before age 5 years and outcome at 5 years was available for up to 1781 subjects. Two GA subgroups (24-27 and 28-32 weeks of GA) were analysed separately. Propensity scores were used to reduce bias in the estimation of the association between ACS treatment and outcomes. MAIN OUTCOME MEASURES: Neonatal death, neonatal white matter injury, cerebral palsy, mental processing composite (MPC) of the Kaufman Assessment Battery for Children test and behavioural difficulties at 5 years. RESULTS: In the 28- to 32-week GA subgroup, there was a significant association between ACS and a decreased risk of both neonatal death (OR = 0.61 [0.41-0.91]) and white matter injury (OR = 0.60 [0.46-0.79]) but only a nonsignificant trend for improved 5-year outcome (cerebral palsy, MPC < 70). In the 24- to 27-week GA subgroup, ACS was associated with a significant decrease risk of neonatal death (OR = 0.43 [0.27-0.68]) but there was only a trend for a lower risk of white matter injury and no beneficial impact on outcome at 5 years. Limiting the analysis to only those who received complete courses of ACS did not modify the results. CONCLUSION: The study shows that ACS therapy greatly increases the survival of very preterm infants, including the most immature, but there is little evidence that ACS affects long-term neurodevelopmental and behavioural outcome in 28- to 32-week survivors, and none in <28-week survivors.

Abstract: AIMS: The standard treatment of neonatal group B Streptococcus infection is intravenous amoxicillin for 10 days. We investigated whether effective serum amoxicillin concentrations could be reached by switching to oral amoxicillin after 48 h of intravenous administration in full-term neonates with group B Streptococcus infection. METHODS: Over 2 years, we included 222 full-term neonates who had early onset group B streptococcal disease responsive to 48 h of intravenous amoxicillin, at which point they were asymptomatic and fed orally. They were switched to oral amoxicillin (300 or 200 mg/kg per day in four divided doses). Steady-state serum amoxicillin concentrations were determined 48 h later by high-performance liquid chromatography; values > or =5 mg/l were considered effective. RESULTS: Mean gestational age was 39.32 +/- 1.5 weeks ,and mean birth weight was 3,422 +/- 533 g; 29 newborns were bacteremic. Median serum amoxicillin concentration on oral therapy was 31,.15 (range 11-118) and 25.80 (range 5-84.8) with 300 and 200 mg/kg per day, respectively. None of the infants had a concentration <5 mg/l (p < 0.001). Gastrointestinal tolerance was satisfactory; 216 patients were discharged at 5 days of age, and none was readmitted within the 3-month follow-up. CONCLUSION: Early switching to the oral route in asymptomatic full-term newborns with early onset group B streptococcal disease maintained serum amoxicillin concentrations within our predefined therapeutic range (error risk<0.001). This strategy may hold potential for reducing treatment invasiveness and shortening hospital length of stay.

Abstract: OBJECTIVE: In a previous multicenter, randomized trial, elective use of high-frequency oscillatory ventilation was compared with the use of conventional ventilation in the management of respiratory distress syndrome in preterm infants <30 weeks. No difference in terms of respiratory outcome was observed, but concerns were raised about an increased rate of severe intraventricular hemorrhage in the high-frequency ventilation group. To evaluate outcome, a follow-up study was conducted until a corrected age of 2 years. We report the results concerning neuromotor outcome. METHODS: Outcome was able to be evaluated in 192 of the 212 infants who survived until discharge from the neonatal unit: 97 of 105 infants of the high-frequency group and 95 of 104 infants of the conventional ventilation group. RESULTS: In the infants reviewed, mean birth weight and gestational age were similar in the 2 ventilation groups. As in the overall study population, the following differences were observed between the high-frequency ventilation group and the conventional ventilation group: lower 5-minute Apgar score, fewer surfactant instillations, and a higher incidence of severe intraventricular hemorrhage. At a corrected age of 2 years, 93 of the 97 infants of the high-frequency group and 79 of the 95 infants of the conventional ventilation group did not present any neuromotor disability, whereas 4 infants of the high-frequency group and 16 infants of the conventional ventilation group had cerebral palsy. CONCLUSIONS: Contrary to our initial concern about the increased rate of severe intraventricular hemorrhage in the high-frequency ventilation group, these data suggest that early use of high-frequency ventilation, compared with conventional ventilation, may be associated with a better neuromotor outcome. Because of the small number of patients studied and the absence of any explanation for this finding, we can conclude only that high-frequency oscillatory ventilation is not associated with a poorer neuromotor outcome.

Abstract: OBJECTIVE: <<Sécurité naissance-Naître ensemble des Pays-de-la-Loire>> network organized a survey to evaluate the incidence rate of early neonatal sudden death or near death syndrome for the full term and healthy presume neonates. METHOD: Maternity wards are declared apparent life-threatening events and deaths from 2001 to 2006. Certain cases and probable cases were defined. Incidence rate have been calculated with births in maternity wards during period... RESULTS: Eleven apparent life-threatening events are observed with 7 deaths during five and half years. The incidence rate was one apparent life-threatening events for 26000 births and one death for 40000 births, with certain cases for 41000 births and probable cases for 71000 births. All kind of maternities were involved. Nothing very special could be noticed about pregnancies and deliveries. Five times on eight well known cases, the newborn was in skin to skin contact with heir mother at the moment of the event, once in her arms and once in the delivery room, far from the mother, at three minutes of life. Twice on four well known cases, newborns were lying on their belly. A baby has been considered as dead at the maternity, ten have been transferred to care unit, and six died in the ward. CONCLUSION: Without systematic survey in France, it's not easy to say if the incidence of this type of event have increased, and if their happening is linked with skin-to-skin practices at the birth. In <<Sécurité naissance-Naître ensemble des Pays-de-la-Loire>> from September 2006, prevent measures have been suggested in all maternities in the recommendation on care to normal newborns. A systematic study with a standard questionary has been organized in region area to notice apparent life-threatening events and neonatal sudden deaths, and we could hope a systematic prospective survey in France.

Abstract: We conducted a prospective study in 215 children, 3 to 36 months of age, presenting with fever > or = 39 degrees C without obvious origin, in order to evaluate the diagnostic value of procalcitonin (PCT) in detection of occult bacteraemia. PCT associated with white blood cell count constitutes an efficient screening method with sensitivity 100%, specificity 61.9% and positive and negative likelihoods ratios of 2.62 and 0, respectively.

Abstract: To gain insight into specific gene expression in the gastrointestinal (GI) tract of preterm infants, we adapted a method to isolate exfoliated epithelial cells. Gastric residual fluid aspirates (n = 89) or stool samples (n = 10) were collected from 96 neonates (gestational age, 24-36 wk). Cells were characterized by microscopic observation, cytokeratin-18 immunodetection, and expression of transcripts. The human origin of cellular DNA was confirmed by amplification of specific X and Y chromosome sequences. Isolation yielded 100-500 cells per sample for gastric aspirates (n = 8) and 10-20 cells for fecal samples (n = 5). Epithelial origin was confirmed by immunodetection of cytokeratin 18. Analyses of reverse transcribed products, using two independent methods, from 15 gastric fluid and two stool samples showed that 18S-rRNA and transcripts of beta-actin, glyceraldehyde-3-phosphate dehydrogenase (gapdh), and period1 were in quantities corresponding to at least 10 cells. On 59 aspirates, we found beta-actin transcripts (all but one), cytokeratin 18 (eight positive of eight samples), SLC26-A7-1 (13 positive of 19 samples), period2 (17 positive of 17 samples), and clock (25 positive of 26 samples). Exfoliated cells can be recovered from gastric aspirates and fecal samples and serve as a tool to investigate the impact of therapeutic and nutritional regimens on the maturation of GI functions.

Abstract: OBJECTIVE: To evaluate the rates of in-hospital death, neonatal complications, and 5-year outcomes of infants born at 30-34 weeks of gestation. METHODS: In nine regions of France, all 2,020 stillbirths and live births at 30, 31, and 32 weeks in 1997 and all 457 births at 33 and 34 weeks in April and October 1997 were recorded. Survivors were evaluated at 5 years of age. RESULTS: Increasing gestational age from 30 to 34 weeks was associated with progressive decreases in in-hospital mortality (from 8.1% to 0.4%) and neonatal complications (respiratory distress syndrome, 43.8% to 2.6%; maternofetal infections, 7.2% to 2.6%; and severe white matter injury, 5.5% to 1.3%). Although infants at 33 and 34 weeks of gestation rarely experienced necrotizing enterocolitis, bronchopulmonary dysplasia, or nosocomial infections, they still required endotracheal ventilation, antibiotics, or parenteral nutrition. At 5 years of age, older gestational age was associated with significant decreases in rates of cerebral palsy (6.3% at 30 weeks and 0.7% at 34 weeks) and mild to severe cognitive impairments (35.3% at 30 weeks and 23.9% at 34 weeks). In singletons, preterm rupture of membranes or preterm labor carried an increased risk of cerebral palsy but not of cognitive impairment. CONCLUSION: Neonates born at 30-34 weeks experienced substantial morbidity and often required admission to neonatal intensive care units. These outcomes suggest that prolonging pregnancies beyond 34 weeks may be desirable whenever possible. Infants born at 30-34 weeks should be carefully monitored to ensure prompt detection and management of neurodevelopmental impairment.

Abstract: OBJECTIVE: To develop an effective outbreak-control strategy by identifying the source and modes of transmission of Staphylococcus capitis in a 60-bed neonatal intensive care unit (NICU). STUDY DESIGN: We conducted a study among neonates hospitalized during the outbreak (June 2000 through November 2003). All cases of S. capitis colonization or infection detected by clinical samples during the outbreak were included. The molecular analysis of the isolated was assessed by pulsed-field electrophoresis. We reported the description of the outbreak and the measures taken during this investigation. RESULT: Thirty-three patients were colonized or infected by S. capitis. Mean gestational age was 28.5+/-4.4 weeks of gestation, mean birth weight was 1068+/-637.3 g and the mean length of hospital stay was 77.9+/-35.9 days. We observed that positive S. capitis cultures were over-represented in six beds of the NICU. Because S. capitis is known to thrive in lipid media, we cultured samples from the almond oil bottles assigned to these beds. S. capitis strain recovered from one of the almond oil sample was genetically identical to the strain recovered from the cases. CONCLUSION: Almond oil is an unusual reservoir infection. Control policy allowed prompt institution of measures that were successful in ending the outbreak.

Abstract: We evaluated the semi-quantitative procalcitonin level for diagnosing late-onset infections in 176 neonates. Using a cut-off level of 0.5ng/ml, the sensitivity was 84.4%+/-0.19, specificity was 93.9%+/-0.04, positive predictive value was 82.6%+/-0.1, and negative predictive value was 94.6%+/-0.04. Procalcitonin could be a useful marker of late-onset infection in neonates.

Abstract: BACKGROUND AND OBJECTIVES: - Follow-up networks for newborns with a handicap risk need to be put into place downstream of the perinatal health networks. Such a network was implemented in the Pays de la Loire region in 2003. Our objective is to evaluate the feasibility and the capacity to detect infants with an incapacitating condition at nine months corrected age and the patents'satisfaction with such a network. MATERIAL AND METHODS: - A common tool based on the Amiel Tison assessment was set up. Infants included since 1(st) March 2003 and who were two years old corrected age on 1(st) September 2006 were taken into consideration. A satisfaction survey was conducted with the parents of infants showing normal development at two years old corrected age or with an abnormal neuromotor examination. RESULTS: - Amongst the 1339 infants included, 1185 (88.4 %) were seen at the age of two years: 7.3 % showed pathological development, 4.5 % infants showed suspect neuromotor examination. Cares were proposed for 11% of the infants followed, permitting cares from nine months old for 65 % of the infants considered as having a pathological development at the age of two years. DISCUSSION/CONCLUSION: - This follow-up network has fulfilled its initial goal: 2.2 % of newborn babies in the region were included, a low rate of lost for follow-up was observed. Moreover, this network has a relative good capacity for detection and early initiation of care. The application of the parents is important and their level of satisfaction appeared to be high. This experiment shows that regional follow-up networks can become reality, but their efficiency still needs to be improved.

Abstract: We report the case of a 29-day-old baby girl in whom Escherichia coli meningitis led to the diagnosis of Currarino syndrome (CS) (OMIM 176450), an autosomal-dominant genetic disorder associated with sacral agenesis, anorectal malformation, presacral masses and spinal cord malformations. Her condition improved with antibiotics and early surgical treatment. A familial study identified other genetically related individuals with similar symptoms.

Abstract: Procalcitonin (PCT) and C reactive protein (CRP) concentrations in umbilical cord blood of 197 neonates were measured to evaluate their value as markers of infection. Sixteen of the neonates were infected. The sensitivity, specificity, and negative and positive predictive values were respectively 87.5%, 98.7%, 87.5%, and 98.7% for PCT and 50%, 97%, 67%, and 94% for CRP. Serum PCT in cord blood seems to be a useful and early marker of antenatal infection.

Abstract: OBJECTIVE: Perinatal regionalization has been organized into 3 ascending levels of care, fitting increasing degrees of pathology. Current recommendations specify that very premature infants be referred prenatally to level III facilities, yet not all very preterm neonates require level III intensive care. The objective of our study was to determine the antenatal factors that, in association with gestational age, predict the need for neonatal intensive care in preterm infants, to match the size of birth with the level of care required. METHODS: Data were analyzed from a cohort of very preterm infants born in nine French regions in 1997. We defined the need for neonatal intensive care as follows: (1) the requirement for specialized management (mechanical ventilation for >48 hours, high frequency oscillation, or inhaled nitric oxide) or (2) poor outcome (transfer to a level III facility within the first 2 days of life or early neonatal death). Triplet pregnancies and pregnancies marked by fetal malformations or intensive care requirements for the mother before delivery were excluded. RESULTS: We focused our study on 1262 neonates aged 30, 31 and 32 weeks' gestation, where the need for intensive care was 42.8%, 33.2%, and 22.8%, respectively. Multivariate analysis showed that the risk factors for intensive care requirement with low gestational age were twin pregnancies, maternal hypertension, antepartum hemorrhage, infection, and male gender. Antenatal steroid therapy and premature rupture of membranes were protective factors against intensive care requirement. CONCLUSION: Infants <31 weeks' gestation should be referred to level III facilities. From 31 weeks' gestation, some infants can be safely handled in level IIb facilities. However, the quality of perinatal regionalization may only be fully assessed by long-term follow-up.

Abstract: AIM: To evaluate the effects of hydroxyethyl starch (6% HES 200/0.5) on cardiac output in hypotensive neonates with low cardiac output and absence of myocardial dysfunction. METHODS: In a prospective randomized blinded trial, 21 hypotensive neonates (mean gestational age of 29+/-3 wk) were randomly allocated to receive infusions of either 5% albumin (albumin group), isotonic saline (saline group) or hydroxyethyl starch (HES group). Infants had to show low cardiac output and an absence of myocardial dysfunction for inclusion in the study. Cardiac output was assessed by Doppler-derived mean aortic flow velocity. RESULTS: Ten minutes after infusion, 67% of all infants had more than a 10% increase in cardiac output. Increases in mean aortic flow velocity (m/s; median and range) were 0.05 (-0.02, +0.07), 0.03 (-0.03, +0.12) and 0.03 (-0.04, +0.11) for the albumin, saline and HES groups, respectively (p = 0.79). The percentage of blood pressure normalization (95% confidence interval) was 86% (60-100) in the albumin group, 57% (20-94) in the saline group and 71% (37-100) in the HES group (p = 0.50). CONCLUSION: This study did not provide evidence that hydroxyethyl starch is more efficient than isotonic saline or albumin.

Abstract: BACKGROUND: We report a case of shock, revealing a severe hypernatremia caused by salt poisoning in a 17-day-old male neonate. OBJECTIVE: We consider the physiopathology of salt overload in this context and the diagnostic strategy in neonate with hypernatremia. METHODS: We used patient history, weight, plasma, and urine osmolality to establish the diagnostic strategy. RESULTS: Salt poisoning in neonates manifests as intracellular dehydration without extracellular fluid accumulation. CONCLUSIONS: This poisoning underscores the need for providing appropriate help to mothers at discharge from the maternity ward or neonatology unit.

Abstract: OBJECTIVE: An adult trial reported the efficacy of recombinant human erythropoietin in critically ill patients with a 19% decrease in red blood cell transfusion. Our aim was to evaluate the relevance of this prophylactic treatment in children hospitalized in a pediatric intensive care unit (PICU). DESIGN: Cohort study from January 1995 to December 2004. SETTING: University hospital PICU. PATIENTS: Children between 1 month and 18 yrs of age. INTERVENTIONS: We searched through a prospective databank for all children hospitalized in the PICU for > or =4 days (potential recipients of erythropoietin, as proposed in the adult trial) and transfused with red blood cells after day 7 following PICU entry (in whom erythropoietin might prevent anemia, according to results of the adult trial). MEASUREMENTS AND MAIN RESULTS: We found that 799 of 2,578 children (31%) were hospitalized for > or =4 days. The study group comprised 787 patients who were hospitalized for > or =4 days in the PICU and for whom full records were available. One hundred eighty-three children in this study group were transfused during their stay in the PICU (median age, 7 months; weight, 6.60 kg). Hemoglobin levels before transfusion (mean +/- sd) were 7.7 +/- 1.5 g/dL. These transfused children represented 23% of the study group and 7% of the total PICU admissions. Forty-seven children (6% of the study group, 2% of the total PICU admissions) were transfused with red blood cells after 7 days of hospitalization and could have benefited from a prophylactic treatment with erythropoietin. Relative risk to benefit of a prophylactic treatment by erythropoietin was higher in cases of mechanical ventilation (relative risk, 1.18) and inotropic treatment (relative risk, 1.72) and if the main diagnosis involved dermatological (relative risk, 3.03) or oncologic disease (relative risk, 3.94). CONCLUSIONS: If we applied the results of the adult trial to our PICU, we would have to treat 31% of the children with prophylactic erythropoietin and thereby expect a reduction of one red blood cell transfusion for every 17 treated patients.

Abstract: OBJECTIVES: To assess the relation between cigarette smoking during pregnancy and neonatal respiratory distress syndrome (RDS) in very preterm birth, and to analyse the differential effect of antenatal steroids on RDS among smokers and non-smokers. DESIGN: A population based cohort study (the French Epipage study). SETTING: Regionally defined births in France. METHODS: A total of 858 very preterm liveborn singletons (27-32 completed weeks of gestation) of the French Epipage study were included in this analysis. The odds ratio for RDS in relation to smoking in pregnancy was estimated using a logistic regression to control for gestational age. The odds ratio for RDS in relation to antenatal steroids was estimated taking into account an interaction between antenatal steroids and cigarette smoking, using multiple logistic regression to control for gestational age, birthweight ratio, main causes of preterm birth, mode of delivery, and sex. RESULTS: The odds ratio for RDS in relation to smoking in pregnancy adjusted for gestational age (aOR) was 0.59 (95% confidence interval (CI) 0.44 to 0.79). The aOR for RDS in relation to antenatal steroids was 0.31 (95% CI 0.19 to 0.49) in babies born to non-smokers and 0.63 (95% CI 0.38 to 1.05) in those born to smokers; the difference was significant (p = 0.04). CONCLUSIONS: Cigarette smoking during pregnancy is associated with a decrease in the risk of RDS in very preterm babies. Although antenatal steroids reduce the risk of RDS in babies born to both smokers and non-smokers, the reduction is smaller in those born to smokers.

Abstract: The correlation of clinical and epidemiological data suggests that intrauterine infection/inflammation can promote foetal lung injury. The aim of this study was: 1) to characterise the early inflammatory response elicited in infected foetal lungs, in terms of nitric oxide-derived oxidative stress and programmed cell death; and 2) to investigate the effects of antibiotic therapy on these parameters. A previously described rabbit experimental model of materno-foetal infection was used. Animals were divided into three groups: controls; Escherichia coli infected (12 h); and E. Coli infected (12 h) and treated (24 h gentamicin+ceftriaxone). Foetal lungs were examined in terms of histology, nitric oxide synthase (NOS) activity, immunohistochemical detection of 3-nitrotyrosine, and detection of apoptotic cells by the TUNEL assay and Hoechst staining. In the infected group, a moderate inflammatory response was observed, associated with a significant increase in inducible NOS activity, the formation of 3-nitrotyrosine residues in epithelial and immune cells, the down-regulation of constitutive NOS activity and clusters of apoptotic cells, as compared with the control group. Early antibiotic therapy, initiated at 12 h post-inoculation, elicited a significant decrease in the infection-induced nitrosative stress. Levels of 3-nitrotyrosine and of apoptotic cells were decreased in the infected-and-treated group compared with the infected group, mainly by the re-expression of constitutive NOS and of the basal level of inducible NOS. Altogether, these findings indicate that early antibiotic therapy can curb the inflammatory reaction and help avert antenatal lung injury, which is known to be involved in the onset of bronchopulmonary dysplasia.

Abstract:

Abstract: OBJECTIVE: To investigate the specific hemodynamic effects of the phosphodiesterase inhibitor milrinone in a rabbit model of septic shock in the absence of any other treatment. DESIGN: A prospective, controlled, interventional study. Animal Model: Fourteen sedated New Zealand rabbits. SETTING: Research laboratory of a health sciences university. INTERVENTIONS: Rabbits were anesthetized and vascular catheters inserted in femoral artery and jugular vein. After a stabilization period and the recording of baseline measurements (H0), all animals received a 10-mL infusion of Pseudomonas aeruginosa. Two hours later (H2rabbits were randomly assigned to receive 5% dextrose (control group) or milrinone (milrinone group). MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure (MAP) was monitored continuously, and a cardiac index (CI) was determined every 30 mins by a transpulmonary thermodilution technique using an integrated monitoring device (PICCO). No differences were detected between the two groups after stabilization (H0) or before the treatment (H2) for either CI (mL/min(-1)/kg(-1)) or MAP (mm Hg). CI decreased progressively in the control group during the following 4 hrs, but not in the treated group (at H6: 122 +/- 4 vs. 207 +/- 16 mL/min(-1)/kg(-1); p < .05). No drop of MAP occurred after milrinone infusion. A comparison of the treated and control group reveals that milrinone improved tissue perfusion as evidenced by measurements of central venous saturation (at H4: 0.59 +/- 0.05 vs. 0.71 +/- 0.03, p = .04), lactacidemia (at H6: 10.3 +/- 2.4 vs. 3.9 +/- 0.9 mmol/L, p = .03), creatinemia (at H6: 95 +/- 11 vs. 60 +/- 5 micromol/L, p = .02) and survival (at H6: 5 vs. 7, not significant). CONCLUSION: Milrinone improves cardiac output and tissue perfusion in a rabbit model involving severe septic shock.

Abstract: OBJECTIVE: The purpose of this study was to examine the relationships between different causes of preterm delivery (eg, maternal hypertension, small-for-gestational age [SGA], other) and cerebral damage (eg, cystic periventricular leukomalacia [c-PVL], grade III intraventricular hemorrhage [IVH], and intra-parenchymal hemorrhage [IPH]). STUDY DESIGN: This study included 1902 very preterm singletons who were transferred to neonatal intensive care units in 9 French regions. We used logistic regression models to compare the risk of cerebral injury associated with maternal hypertension, SGA, and all other causes of preterm delivery. RESULTS: We found that the risk of c-PVL and grade III IVH was higher in infants born after preterm premature rupture of membranes (PPROM) with short latency or idiopathic preterm labor than in infants born to hypertensive mothers. We show that SGA and antepartum maternal hemorrhage significantly increase the risk of IPH. CONCLUSION: Our results show that infants born to hypertensive mothers have a lower risk of cerebral injuries than infants born following idiopathic preterm labor and PPROM because they are less exposed to prenatal infection.

Abstract: OBJECTIVE: To identify the main prenatal risk factors for cerebral palsy in very preterm singletons and twins. METHODS: The data were from the Epipage study, which included all very preterm children (< 33 weeks) born in 1997 in 9 regions of France. The analysis included 1,954 children for whom a medical questionnaire was completed at the age of 2 years (83% of the surviving children). The risk factors studied were pregnancy complications and specific factors in twins (type of placenta and death of cotwin). Logistic regression analysis was carried out for singletons and generalized estimating equation models used for twins. RESULTS: The proportion of cerebral palsy was 8% in singletons and 9% in twins. For singletons, spontaneous preterm labor (adjusted odds ratio [OR] 3.4, 95% confidence interval [CI] 1.7-6.7), preterm premature rupture of membranes (PPROM) with short latency (adjusted OR 4.9, 95% CI 2.0-11.8), and prolonged PPROM (adjusted OR 2.7, 95% CI 1.4-5.3) were associated with a higher risk of cerebral palsy than was hypertension. No such link was found between these pregnancy complications and cerebral palsy in twins. For twins, a monochorionic placenta (OR 1.9, 95% CI 1.0-3.6) increased the risk of cerebral palsy, but the OR became nonsignificant after adjustment (OR 1.7, 95% CI 0.8-3.4). CONCLUSION: In very preterm singletons, spontaneous preterm labor and PPROM increased the risk of cerebral palsy compared with hypertension.

Abstract: Tetraplegia developed abruptly in an 11-y-old with pneumococcal meningitis. Magnetic resonance imaging showed multiple hyperintensities at the brainstem-spinal cord junction. Serological tests were positive for Mycoplasma pneumoniae (microparticle agglutination and specific IgMs). Erythromycin and dexamethasone were started promptly, and 10 d later the patient was discharged with normal neurological function. CONCLUSION: Tetraplegia during the course of pneumococcal meningitis in an 11-y-old girl disappeared after treatment with ceftriaxone, erythromycin and dexamethasone.

Abstract: OBJECTIVES: To evaluate the risk of very preterm birth (22-32 weeks of gestation) associated with previous induced abortion according to the complications leading to very preterm delivery in singletons. DESIGN: Multicentre, case-control study (the French EPIPAGE study). SETTING: Regionally defined population of births in France. SAMPLE: The sample consisted of 1943 very preterm live-born singletons (< 33 weeks of gestation), 276 moderate preterm live-born singletons (33-34 weeks) and 618 unmatched full-term controls (39-40 weeks). METHODS: Data from the EPIPAGE study were analysed using polytomous logistic regression models to control for social and demographic characteristics, lifestyle habits during pregnancy and obstetric history. The main mechanisms of preterm delivery were classified as gestational hypertension, antepartum haemorrhage, fetal growth restriction, premature rupture of membranes, idiopathic preterm labor and other causes. MAIN OUTCOME MEASURES: Odds ratios for very preterm birth by gestational age and by pregnancy complications leading to preterm delivery associated with a history of induced abortion. RESULTS: Women with a history of induced abortion were at higher risk of very preterm delivery than those with no such history (OR + 1.5, 95% CI 1.1-2.0); the risk was even higher for extremely preterm deliveries (< 28 weeks). The association between previous induced abortion and very preterm delivery varied according to the main complications leading to very preterm delivery. A history of induced abortion was associated with an increased risk of premature rupture of the membranes, antepartum haemorrhage (not in association with hypertension) and idiopathic spontaneous preterm labour that occur at very small gestational ages (< 28 weeks). Conversely, no association was found between induced abortion and very preterm delivery due to hypertension. CONCLUSION: Previous induced abortion was associated with an increased risk of very preterm delivery. The strength of the association increased with decreasing gestational age.

Abstract: OBJECTIVE: To assess the relationship between cigarette smoking during pregnancy and very preterm births, according to the main mechanisms of preterm birth. DESIGN: Case-control study (the French Epipage study). SETTING: Regionally defined population of births in France. POPULATION: Eight hundred and sixty-four very preterm live-born singletons (between 27 and 32 completed weeks of gestation) and 567 unmatched full-term controls. METHODS: Data from the French Epipage study were analysed using a polytomous logistic regression model to control for social and demographic characteristics, pre-pregnancy body mass index and obstetric history. The main mechanisms of preterm delivery were classified as gestational hypertension, antepartum haemorrhage, premature rupture of membranes, spontaneous preterm labour and other miscellaneous mechanisms. MAIN OUTCOME MEASURES: Odds ratios for very preterm birth for low to moderate (1-9 cigarettes/day) and heavy (>/=10 cigarettes/day) maternal smoking in pregnancy, estimated according to the main mechanisms leading to preterm birth. RESULTS: Smokers were more likely to give birth to very preterm infants than non-smokers [adjusted odds ratio (aOR) 1.7, 95% confidence interval (CI) 1.3-2.2]. Heavy smoking significantly reduced the risk of very preterm birth due to gestational hypertension (aOR 0.5, 95% CI 0.3-1.0), whereas both low to moderate and heavy smoking increased the risk of very preterm birth due to all other mechanisms (aOR between 1.6 and 2.8). CONCLUSION: These data from the Epipage study show that maternal smoking during pregnancy is a risk factor for very preterm birth. The impact of maternal smoking on very preterm birth appears to be complex: it lowers the risk of very preterm birth due to gestational hypertension, but increases the risk of very preterm birth due to other mechanisms. These findings might explain why maternal smoking is more closely related to preterm birth among multiparous women than among nulliparous women.

Abstract: Newborns are given attentive perinatal care but the organization of further follow-up can be haphazard. The main consequences are the difficulties parents have in finding appropriate medical assistance for caring for high-risk infants and the absence of appropriate surveillance or efficient care. An inpatient-outpatient healthcare network enables early care of these infants and can reduce the consequences of neurosensorial sequelae. The overall impact of the regional perinatal care can also be evaluated. Such a network has been implemented in the Pays de Loire region in France since early 2003. In six months, among 1000 initially included infants, 500 were followed by pediatricians working in an outpatient (40%) or inpatient (60%) setting. This organization enables correction of over-centralization of neonatal care and the absence of coordination for follow up.

Abstract: OBJECTIVE: To evaluate the outcome for all infants born before 33 weeks gestation until discharge from hospital. DESIGN: A prospective observational population based study. SETTING: Nine regions of France in 1997. PATIENTS: All births or late terminations of pregnancy for fetal or maternal reasons between 22 and 32 weeks gestation. MAIN OUTCOME MEASURE: Life status: stillbirth, live birth, death in delivery room, death in intensive care, decision to limit intensive care, survival to discharge. RESULTS: A total of 722 late terminations, 772 stillbirths, and 2901 live births were recorded. The incidence of very preterm births was 1.3 per 100 live births and stillbirths. The survival rate for births between 22 and 32 weeks was 67% of all births (including stillbirths), 85% of live births, and 89% of infants admitted to neonatal intensive care units. Survival increased with gestational age: 31% of all infants born alive at 24 weeks survived to discharge, 78% at 28 weeks, and 97% at 32 weeks. Survival among live births was lower for small for gestational age infants, multiple births, and boys. Overall, 50% of deaths after birth followed decisions to withhold or withdraw intensive care: 66% of deaths in the delivery room, decreasing with increasing gestational age; 44% of deaths in the neonatal intensive care unit, with little variation with gestational age. CONCLUSION: Among very preterm babies, chances of survival varies greatly according to the length of gestation. At all gestational ages, a large proportion of deaths are associated with a decision to limit intensive care.

Abstract: BACKGROUND: Patent ductus arteriosus is a common complication of prematurity that frequently requires surgical or medical treatment. The benefit of prophylactic treatment by indometacin, a cyclo-oxygenase inhibitor, remains uncertain compared with curative treatment. This benefit could be improved with ibuprofen, another cyclo-oxygenase inhibitor with fewer adverse effects than indometacin on renal, mesenteric, and cerebral perfusion. We aimed to compare prophylactic and curative ibuprofen in the treatment of this abnormality in very premature infants. METHODS: We did a randomised controlled trial in infants younger than 28 weeks of gestation, who were randomly assigned to receive either three doses of ibuprofen or placebo within 6 h of birth. After day 3, symptomatic patent ductus arteriosus was treated first by open curative ibuprofen, then back-up indometacin, surgery, or both. The primary endpoint was need for surgical ligation. Analysis was per protocol. FINDINGS: The study was stopped prematurely after 135 enrollments because of three cases of severe pulmonary hypertension in the prophylactic group. 65 infants received prophylactic ibuprofen, and 66 received placebo. Prophylaxis reduced the need for surgical ligation from six (9%) to zero (p=0.03), and decreased the rate of severe intraventricular haemorrhage from 15 (23%) to seven (11%) (p=0.10). However, survival was not improved (47 [71%] placebo vs 47 [72%] treatment, p=1.00), because of high frequency of adverse respiratory, renal, and digestive events. INTERPRETATION: In premature infants, prophylactic ibuprofen reduces the need for surgical ligation of patent ductus arteriosus, but does not reduce mortality or morbidity. Therefore, it should not be preferred to early curative ibuprofen.

Abstract: Advances in prenatal care have improved survival rates in extremely preterm newborns, but cerebral palsy rates have not decreased in developed countries over the past 30 years. During the next 10 years we will probably not observe a dramatic improvement in intensive care such as that observed over the last 15 years. The man goal for the coming years will be to improve the quality of neonatal and postdischarge care in order to improve the long-term outcomes of very preterm infants.

Abstract: The clinical features of Prader-Willi Syndrome (PWS) in the neonate are marked by hypotonia, absence of crying, and feeding difficulties, but the clinical nature of PWS in utero remains unclear. We report a case of PWS with fetal immobility and distal arthrogryposis in a girl admitted the first day of life to the neonatal intensive care unit for severe hypotonia and respiratory distress.

Abstract: Necrotizing enterocolitis (NEC) is among the most severe conditions that can affect preterm infants. Although the etiology of NEC remains unknown, initial bacterial colonization could play a pivotal role in the development of NEC. To further explore the putative relationship between pathogen microorganisms and NEC, we conducted a prospective case-control study in 12 preterm infants with a new approach based on molecular techniques. Over an inclusion period of 24 mo, 12 neonates of <34 wk gestational age admitted to the neonatal unit were enrolled. The group included three cases of NEC, and nine control infants without evidence of NEC who were matched for gestational age and birth weight. Stool samples were collected at weekly intervals from all infants. PCR and temporal temperature gradient gel electrophoresis of 16S ribosomal DNA were used to detect the establishment of bacterial communities in the digestive tract. A salient feature of the bacteriological pattern was observed only in the three infants who later developed NEC: A band corresponding to the Clostridium perfringens subgroup could be detected in early samples, before diagnosis. There was no evidence for this specific band in any of the nine controls. To our knowledge, the current report is the first to demonstrate that the use of molecular techniques based on the study of bacterial 16S rRNA genes allowed the recognition of C. perfringens species in the first 2 wk of life of three infants who later displayed symptoms of NEC. A significant temporal relationship was thus established between early colonization by Clostridium and the later development of NEC. Compared with conventional bacteriological culturing methods, the use of this new molecular approach to analyze the gastrointestinal ecosystem should therefore allow a more complete and rapid assessment of intestinal flora. Although the current data do not constitute definitive proof that the identified bacterial species was a causative agent in the development of NEC, they outline the promise of this new technique based on molecular biology, and suggest that large-scale studies on a much wider population at high risk for NEC may be warranted.

Abstract: The objective of the present study was to evaluate the pharmacokinetic parameters for both S- and R-ibuprofen enantiomers in very premature neonates (gestational age strictly inferior to 28 weeks) and possible relationships between the pharmacokinetic parameters and various covariates. Newborns were randomized to receive ibuprofen or placebo for the prophylactic treatment of patent ductus arteriosus (PDA) at an initial dose of 10 mg/kg ibuprofen within 6 hours after birth, followed by two 5-mg/kg doses at 24-hour intervals (n = 52). If a PDA was still present afterwards, a curative course of ibuprofen using the same dosage regimen was administered (n = 10). A sparse sampling strategy was used because only 2 samples were collected after the third prophylactic injection and 1 after the third curative injection. A model including the chiral transformation of R- to S-ibuprofen was fitted to the concentration-time data using a population approach (NONMEM). R- and S-ibuprofen t(1/2) were about 10 hours and 25.5 hours, respectively. After prophylactic treatment, the mean clearance of R-ibuprofen (CLR = 12.7 mL/h) was about 2.5-fold higher than for S-ibuprofen (CLS = 5.0 mL/h). In addition, clearance of R- and S-ibuprofen increased significantly with gestational age. The mean estimation of R-ibuprofen clearance was found to be higher than for S-ibuprofen, and the clearance of both enantiomers increased with gestational age. This should be considered to assess pharmacokinetic-pharmacodynamic relationships of ibuprofen in premature neonates and subsequently to understand and refine the use of ibuprofen in managing PDA either as a prophylactic or curative treatment.

Abstract: AIM: To evaluate the effects of maternal antibiotic treatment on fetal brain cell death in a rabbit intrauterine infection model. METHODS: After Escherichia coli uterine-horn inoculation in 22 pregnant rabbits, followed at various times by ceftriaxone and caesarean section, cell death in white matter (histology and fragmented DNA staining) from fetuses killed at extraction was compared across groups using the Mantel-Haenszel test and Fisher's exact test for small numbers. RESULTS: White matter cell death was consistently present at 48 h, with ceftriaxone initiation at 24 h (group 1), detectable at 84 but not 60 h, with ceftriaxone initiation at 12 h, and significantly reduced at 84 h with ceftriaxone initiation at 6 h (60% vs 100% in group 1, p < 0.001, Fisher's exact test). CONCLUSION: Early maternal antibiotic therapy delays white matter cell death in rabbit fetuses exposed to intrauterine infection. This may provide a window for preventing white matter damage.

Abstract: OBJECTIVES: To compare the accuracy of ultrasonography (US) and magnetic resonance imaging (MRI) in diagnosing white matter abnormalities in preterm infants and to determine the specific indications for MRI. DESIGN: Prospective cohort study. SETTING: A neonatal intensive care unit in France. PATIENTS: All preterm infants (</= 33 weeks gestation) without severe respiratory distress syndrome precluding MRI. MAIN OUTCOME MEASURES: US and MRI performed contemporaneously during the third postnatal week were analysed by an independent observer. The findings were compared with those of a term MRI scan, the results of which were taken as the final diagnosis. Statistical analysis was performed to determine which early imaging study best predicted the term MRI findings. RESULTS: The early US and MRI findings (79 infants) correlated closely for severe lesions (cystic periventricular leucomalacia and parenchymal infarction; kappa coefficient = 0.86) but not for moderate lesions (non-cystic leucomalacia and parenchymal punctate haemorrhages; kappa = 0.62). Overall, early MRI findings predicted late MRI findings in 98% of patients (95% confidence interval (CI) 89.5 to 99.9) compared with only 68% for early US (95% CI 52.1 to 79.2). CONCLUSIONS: US is highly effective in detecting severe lesions of the white matter in preterm infants, but MRI seems to be necessary for the diagnosis of less severe damage. MRI performed at about the third week of life is highly predictive of the final diagnosis at term.

Abstract: OBJECTIVE: To evaluate the prevalence of cranial ultrasound abnormalities in very preterm infants as a function of gestational age, plurality, intrauterine growth restriction, and death before discharge. STUDY DESIGN: A prospective, population-based cohort of 2667 infants born between 22 and 32 weeks of gestation in 1997 in nine regions of France, transferred to a neonatal intensive care unit, for whom at least one cranial ultrasound scan was available. RESULTS: The frequencies of white matter damage (WMD), major WMD, cystic periventricular leukomalacia (PVL), periventricular parenchymal hemorrhagic involvement, and intraventricular hemorrhage with ventricular dilatation were 21%, 8%, 5%, 3%, and 3%, respectively. The risk of WMD increased with decreasing gestational age. Mean age at diagnosis of cystic PVL was older for the most premature infants. Intraventricular hemorrhage with ventricular dilatation was associated with a higher risk of cystic PVL. Intrauterine growth restriction was not associated with a lower prevalence of cystic PVL. CONCLUSION: The frequency of WMD is high in very preterm babies and is strongly related to gestational age. The incidence of cystic PVL did not differ between babies with intrauterine growth restriction and babies who were appropriate for gestational age.

Abstract: Although the fetal inflammatory response syndrome seems crucial to the association between intrauterine infection and white matter disease in human preterm infants, the underlying mechanisms remain unclear. Using our previously described rabbit model of cerebral cell death in the white matter and hippocampus induced by intrauterine Escherichia coli infection, we investigated inflammatory and astroglial responses in placenta and brain tissues, in correlation with cell death distribution. Brains and placentas were studied 12, 24, or 48 h following intrauterine inoculation of E. coli or saline (groups G12, G24, and G48). Diffuse monocyte-macrophage infiltrates positive for inducible nitric oxide synthase (i-NOS) were significantly more marked in G24 and G48 placentas than in controls. In the G48 fetuses with both diffuse cell death and focal periventricular white matter cysts mimicking cystic periventricular leukomalacia, a strong rabbit macrophage and inducible nitric oxide synthase immunostaining was observed at the border of these cystic lesions. In contrast, in the fetuses with only diffuse and significant cell death, no inflammatory or astroglial responses were detected in the white matter or hippocampus. Cell death was accompanied by i-NOS immunostaining in the hippocampus but not the white matter. Hippocampal cells positive for i-NOS usually displayed a neuronal phenotype. In this model, focal white matter cysts are accompanied by a robust inflammatory response, and diffuse cell death, which may mimic the white matter and hippocampal damage seen in very and extremely pre-term infants, occur in the absence of a detectable brain inflammatory response.

Abstract: The effect of optimized maternal therapy by bactericidal agents was evaluated in a reproducible rabbit model of Escherichia coli maternofetal infection simulating human pharmacokinetics. Intravenous antibiotic therapy was begun in the pregnant rabbit 12 h after bacterial intrauterine inoculation, using a computer-controlled pump to simulate human pharmacokinetics of ceftriaxone (1 g/day) associated or not with gentamicin (3 mg/kg of body weight/day). Data were compared for fetal survival, quantitative blood cultures, fetal histology in treated versus untreated groups, and maternal and fetal antibiotic concentrations in plasma in treated animals. Antibiotic therapy led to dramatic improvement in maternal outcome (100% survival versus 100% death in the untreated group in association with maternal septicemia). Fetal survival also improved, with the two-drug combination providing a more potent effect. After 3 days of treatment, 32% of fetuses survived with one-drug therapy and 62% with two-drug therapy (Yates corrected chi(2), P < 0.05). In untreated animals, bacterial counts in blood cultures increased rapidly during the first 24 h up to 8.1 +/- 0.5 log CFU/ml, but remained relatively constant at all times with antibiotic treatment: 4.5 +/- 0.7 log CFU/ml at the start of treatment and 6.2 +/- 0.4 and 5.2 +/- 0.9 log CFU/ml after 72 h for one- and two-drug therapy, respectively (data are means +/- standard deviations). The failure of animals to be cured after 3 days of treatment was not due to an inadequate concentration of ceftriaxone, as the residual level in fetal serum at sacrifice was more than 1000 times the MIC of the microbe. Unexpectedly, inflammation in fetal lung decreased in the treated group after as little as 24 h of antibiotic therapy, despite persistent bacteremia. Although maternal outcome improved and drug concentrations were above the MIC, the treatment did not achieve sterilization of fetuses in utero for this rabbit E. coli maternofetal infection. However, fetal survival showed some improvement, and the histologic features of lung inflammation were reduced.

Abstract: An environmental investigation and a cohort study were carried out to analyse an outbreak of infection caused by a serotype O10 Pseudomonas aeruginosa in a neonatal intensive care unit. Thirty one cases of infection were recorded, including four lethal ones. The outbreak was stopped by eradicating the environmental sources: a contaminated milk bank pasteuriser and bottle warmer.

Abstract: OBJECTIVE: To study the renal effects (measured by creatininemia) of plasma volume expansion with a medium molecular weight hydroxyethyl starch in the newborn. DESIGN: A prospective, randomized, double-blinded, pilot study. PATIENTS: The study included 26 neonates weighing 690-4030 g (gestational age, 26-40 wks), without cardiac or renal failure or major hemostasis abnormalities and requiring a peripherally inserted central catheter for parenteral nutrition. SETTING: Pediatric and neonatal intensive care unit of a university-affiliated hospital. INTERVENTIONS: Plasma volume expansion was performed to facilitate insertion of the central catheter. After parental consent, neonates were randomly allocated to receive intravenous infusions at 10 mL.kg(-1) of 5% albumin or 6% hydroxyethyl starch 200/0.5. Sample size was calculated to detect an increase in mean creatininemia of >20 micromol.L(-1) (with alpha = 0.05, beta = 0.80). MEASUREMENTS AND MAIN RESULTS: No clinically or statistically significant differences were found between the two groups 6 hrs, 24 hrs, 48 hrs, and 7 days after plasma volume expansion. The study could detect an increase in creatininemia > or =20 micromol.L(-1) with a power of 80%. CONCLUSIONS: In 13 healthy neonates, plasma volume expansion with 10 mL.kg(-1) of 6% hydroxyethyl starch 200/0.5 does not increase creatininemia.

Abstract: We investigated the effects of dopamine on pulmonary artery pressure in 18 ventilated hypotensive preterm neonates by using the flow characteristics of the ductal shunt. Dopamine has variable effects on pulmonary/systemic mean arterial pressure ratio with half the neonates showing an increase in pulmonary pressure relative to systemic pressure.

Abstract: Although very low birth weight infants are subjected to severe stress and glutamine is now considered a conditionally essential amino acid that may attenuate stress-induced protein wasting in adults, current amino acid solutions designed for neonatal parenteral nutrition do not contain glutamine. To determine whether a short-term supplementation with i.v. glutamine would affect protein metabolism in very low birth weight infants, 13 preterm neonates (gestational age, 28-30 wk; birth weight, 820-1610 g) receiving parenteral nutrition supplying 1.5 g x kg(-1) x d(-1) amino acids and approximately 60 nonprotein kcal x kg(-1) x d(-1) were randomized to receive an i.v. supplement made of either 1) natural L-glutamine (0.5 g x kg(-1) x d(-1); glutamine group), or 2) an isonitrogenous glutamine-free amino acid mixture (control group), for 24 h starting on the third day of life. On the fourth day of life, they received a 2-h infusion of NaH(13)CO(3) to assess the recovery of (13)C in breath, immediately followed by a 3-h L-[1-(13)C]leucine infusion. Plasma ammonia did not differ between the groups. Glutamine supplementation was associated with 1) higher plasma glutamine (629 +/- 94 versus 503 +/- 83 microM, mean +/- SD; p < 0.05, one-tailed unpaired t test), 2) lower rates of leucine release from protein breakdown (-16%, p < 0.05) and leucine oxidation (-35%, p < 0.05), 3) a lower rate of nonoxidative leucine disposal, an index of protein synthesis (-20%, p < 0.05), and 4) no change in protein balance (nonoxidative leucine disposal - leucine release from protein breakdown, NS). We conclude that although parenteral glutamine failed to enhance rates of protein synthesis, glutamine may have an acute protein-sparing effect, as it suppressed leucine oxidation and protein breakdown, in parenterally fed very low birth weight infants.

Abstract: Refractory hypoxemia in the newborn requires an accurate diagnostic investigation for an optimal and prompt management. CASE REPORT: After a short delivery, a post-term newborn developed a severe hypoxemia with patchy pulmonary alveolar opacities and systolic right-to-left extrapulmonary shunting through the ductus arteriosus. Echocardiography ruled out a cardiac malformation and showed dilated left atrium with left-to-right shunting by the ovale foramen due to left ventricular dysfunction. Inotropic support associated with mechanical ventilation allowed a rapid improvement. CONCLUSION: A pathophysiological analysis is needed in case of severe neonatal hypoxemia. Doppler ultrasound is a non invasive and rapid method allowing the adjustment of the therapeutic strategy.

Abstract: The prophylactic administration of Palivizumab, a monoclonal antibody binding the respiratory syncytial virus (RSV) fusion protein, was recently shown to significantly decrease the incidence of RSV-related hospitalizations among high-risk children (IMpact-RSV trial). While awaiting marketing authorization in France and through a cohort of patients' name-based national program temporarily authorized by the French Drug Agency, a prospective register of all Palivizumab-treated patients in France was set up during the epidemic season 1999-2000. Based on this register, this study was carried out to evaluate the incidence of RSV-related hospitalizations and the safety of prophylaxis among a national cohort of children at high-risk of severe RSV disease. During the study period, guidelines issued by the French Pediatric Society recommended prophylaxis for children either aged less than 6 months at inclusion and born at less than 33 weeks of gestation with a history of bronchopulmonary dysplasia (BPD) at 28 days of life, or aged less than 2 years, born at less than 36 weeks of gestation, and having required treatment for BPD over the previous 6 months. Once included in the program, investigators were to prospectively report the clinical and demographic characteristics of children, all hospitalizations, and reasons for the hospitalizations. Five hundred and sixteen children were treated with 1-5 monthly doses. The median gestational age was 28 weeks, and children born at less than 33 weeks of gestation accounted for 88% of the cohort. The prevalence of BPD was 81%. Ninety children were hospitalized for respiratory illness. In 39 children, hospitalizations were attributed to RSV (7.6% of the total cohort). Among those 39 children, 10 (1.9% of the total cohort) required admission into an intensive care unit, and 4 required mechanical ventilation. No deaths or serious adverse events attributable to RSV infection or Palivizumab treatment were reported. We conclude that the RSV-related hospitalization rate in this high-risk cohort was comparable to the rate observed in the subgroup of Palivizumab-prophylaxed children with BPD in the IMpact-RSV trial.

Abstract: We report three cases of severe hypoxaemia after ibuprofen administration during a randomised controlled trial of prophylactic treatment of patent ductus arteriosus with ibuprofen in premature infants born at less than 28 weeks of gestation. Echocardiography showed severely decreased pulmonary blood flow. Hypoxaemia resolved quickly on inhaled nitric oxide therapy. We suggest that investigators involved in similar trials pay close attention to pulmonary pressure if hypoxaemia occurs after prophylactic administration of ibuprofen.

Abstract: AIM: To study baroreflex maturation by measuring, longitudinally, baroreflex sensitivity in preterm (gestational age 24-37 weeks) and full term infants. METHODS: Baroreflex sensitivity was quantified once a week, one to seven times, by a totally non-invasive method. RESULTS: Baroreflex sensitivity at birth was lower in the preterm infant and increased with gestational age. It also increased with postnatal age, but the values for the preterm infants at term still tended to be lower than the values for full term babies. CONCLUSION: Baroreflex control of heart rate is present in the premature infant, but is underdeveloped and increases with postnatal age. Ex utero maturation seems to be delayed compared with in utero maturation assessed by full term values. These results may reflect sympathovagal imbalance in preterm infants and could identify a population more vulnerable to stress.

Abstract: Since the regionalization of perinatal services and the laws on the safety of child-birth were announced on the 9th October 1998, conventions and rules establishing relationships between doctors in perinatal networks have gradually been set up. In order to assess the impact, functioning and effectiveness of this care organisation on the health of mothers an childs, a common study design is essential. Such a common protocol, with the same methodology, allows the comparison of observed results from one perinatal network to another. With this objective, four leading societies in the field, the French National College of Gynaecologists and Obstetricians (CNGOF), the National Federation of Neonatal Pediatricians (FNPN), the French Society of Perinatal Medicine (SFPM) and the Association of Computerised Medical Records in Perinatalogy, Obstetrics and Gynaecology (AUDIPOG) set up a workshop in order to elaborate a common text, which was adopted by the Administrative Councils of the four societies. This contractual text, co-operatively elaborated, is now introduced to the scientific community. It was prepared from scientific papers and international recommendations in the field of perinatal regionalization, leading to a protocol giving information on objectives, study population, study design and assessment criteria. For this, a list of questions was proposed, including the impact of perinatal network, its acceptability by doctors and families, its functioning and its effectiveness on the health of mother and child. The means of data collection were then presented, whether from institutional sources of perinatal data (completed from specific registers or studies), or from the information system France-Perinat, especially designed for the evaluation of the perinatal networks.

Abstract: We report two foetal complications after amnioinfusion with dye injection for evaluation of severe oligohydramnios in pregnancy. In the first case, an underskin colouring was to disappear within a few days. In the second case, an irreversible skin after-effect with muscular atrophy and lesion of the underskin tissues developed progressively, although the trained practitioner did not notice any particular resistance during the injection of the dye and the ultrasonographer did not point out that the foetus had been stuck by the needle.Both later reported cases concern two life threatening maternal complications due to amniocentesis for foetal karyotyping indicated by maternal age, a septic shock occurred 24h after entering the amniotic cavity, leading to a long stay in intensive care units. In one of those cases, the patient recovered from a cardiac arrest.We come to the conclusion that the essential continuous ultrasonographic monitoring cannot avoid all complications, some of which may lead to severe adverse foetal effects and others may need an intensive medical care for the mother, mainly after iatrogenic chorioamnionitis. Experience of the perinatologist remains an important factor to limit the complications without avoiding them completely. The indications must be carefully evaluated, the information given to the patients must be clear and in the future, intraamniotic injections of dyes will have to be avoided and replaced by non-invasive tests for diagnosis of preterm premature rupture of membranes, such as diamine-oxidase, foetal fibronectin or PROM-tests. The rules of a good practice will have to be defined and widely spread.

Abstract: An association between chorioamnionitis and periventricular leukomalacia has been reported in human preterm infants. However, whether this link is causal has not been convincingly established, and the underlying molecular mechanisms remain unclear. The objective of this study was to establish a reproducible model of cerebral white matter disease in preterm rabbits after intrauterine infection. Escherichia coli was inoculated into both uterine horns of laparotomized pregnant rabbits when gestation was 80% complete. The fetuses were delivered by cesarean section and killed 12, 24, or 48 h after the inoculation. Programmed cell death in the white matter was evaluated by hematoxylin-eosin-saffron staining and in situ fragmented DNA labeling (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). In a first group of 14 pregnant rabbits not treated with antibiotics, all fetuses delivered 48 h after inoculation were stillborn, whereas fetuses extracted 12 or 24 h after inoculation were alive. No significant cell death was detected in the live fetuses compared with the control noninfected rabbits. In a second group of five pregnant rabbits treated with ceftriaxone initiated 24 h after the inoculation and continued until cesarean section was performed 48 h after inoculation, 13 fetuses were alive, but all showed evidence of extensive programmed cell death in the white matter by hematoxylin-eosin-saffron staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. White matter damage became histologically detectable only 48 h after inoculation. Three of the 13 brains displayed periventricular white matter cysts mimicking human cystic periventricular leukomalacia. The high reproducibility of white matter damage in our model should permit further studies aimed at unraveling the molecular mechanisms of periventricular leukomalacia.

Abstract: AIM: Evaluation of the progress in the treatment of seriously ill newborn infants under hospital care over the nine-year period from 1986 to 1995 in three departments of the Pays de la Loire region in France. POPULATION AND METHODS: The category of seriously ill newborn infants included only infants born after at least 32 weeks of gestation and having a Cullen severity score higher than 2. The two groups of seriously ill newborn infants at risk in 1986 and 1995 were first compared to a control group of healthy newborn babies delivered during the same years. The two groups were then compared with each other. RESULTS: In 1986 and 1995, the numbers of births were respectively 32,876 and 29,446, and the numbers of seriously ill newborn infants under hospital care were respectively 307 and 245. However, between 1986 and 1995 the risk factors as well as the causes of morbidity had changed. The average period of hospitalization decreased by five days. The mortality rate dropped from 0.16% to 0.09% (P < 0.05) and the number of serious complications decreased from 0.07% to 0.03% (P < 0.05). CONCLUSION: The improvement in the care of seriously ill newborn infants between the two reference periods, 1986 and 1995, may be attributed not only to technical progress but also to a better organization of the perinatal care in our region.

Abstract: Neonatal hemochromatosis is characterized by abnormal hepatic and extrahepatic iron overload, which spares the reticuloendothelial system. In neonates, hemochromatosis results in an acute and frequently lethal liver failure. CASE REPORTS: We report five cases of neonatal hemochromatosis which demonstrate various aspects of this disorder and underline the complexity of both the diagnosis and treatment. Case 3 had an extremely low arterial pressure, a presentation not yet described. CONCLUSION: Neonatal hemochromatosis should be suspected in the presence of cholestasis with liver failure of perinatal onset and with high blood level ferritin. Abdominal nuclear magnetic resonance and/or liver biopsy can confirm neonatal hemochromatosis. For one of our patients, a medical treatment allowed us to perform a liver transplantation.

Abstract: BACKGROUND: The Pays de Loire has a low perinatal mortality indicators among French regions but this could be due to under-notification. OBJECTS: To explore this hypothesis we undertook a survey in order to identify all fetal and neonatal deaths occurring at a gestionnal age of 22 weeks or more. We also tried to examine and analyze the causes of death. METHODS: All maternity (26) and neonatal wards (5) in the region took part in the survey in 1995. Clinicians were asked to fill out a questionnaire for all deaths occurring from gestational age (GA) 22 weeks and/or concerning a birthweight of a least 500 g. Only perinatal deaths related to parents living in the Pays de Loire were included in the study. RESULTS: Two hundred and sixty seven perinatal deaths were identified out of a total 29,440 births (9.1 /1000). Eighty three (2.8 /1000) were termination of pregnancy for medical reasons, of which 82% were motivated by chromosomic illness. Ninety-nine stillbirths fell (3.4 /1000) into two GA periods: 24 to 27 weeks (20%) and 38 to 41 weeks (2%). The cause of stillbirths remained unknown in 50% of cases despite a post-mortem examination rate of 87%. There were 29 deaths (1 /1000) in the immediate per and post-partum, 40% of which occurred at GA 22 to 25 weeks. Another 38% occurred at GA 36 to 40 weeks and these were related to undectected malformations or infections. Neonatal and intensive care units reported 56 neonatal deaths (1.9 /1000). GA was under 33 weeks for 44% of them. Deaths were caused by usual complications of severe prematurity, neurologic diseases and malformations. Thirty-two percent of total deaths were not notified to the French Authority: 25% of deaths for termination of pregnancy for medical reasons and 7% for stillbirths and per and post partum deaths. CONCLUSION: This survey suggests that the Pays de Loire perinatal mortality indicators remained low compared with other French regions, even after adjustment for this under notification. This casts doubts on the validity of perinatal mortality monitoring based on official notifications. The cause may lie in the inadequacy of legislation of the particular circumstances of perinatal deaths.

Abstract: BACKGROUND: Although medium-chain triacylglycerols (MCTs) may be utilized more efficiently than long-chain triacylglycerols (LCTs), their effect on protein metabolism remains controversial. OBJECTIVE: The aim of the study was to compare the effects of mixed MCT-LCT and pure LCT emulsions on leucine metabolism in preterm infants. DESIGN: Fourteen preterm [gestational age: 30+/-1 wk; birth weight: 1409+/-78 g (x +/- SE)] neonates were randomly assigned to receive, from the first day of life, either a 50:50 MCT-LCT (mixed MCT group; n = 7) or an LCT (LCT group; n = 7) lipid emulsion as part of an isonitrogenous, isoenergetic total parenteral nutrition program. On the fourth day, infants received intravenous feeding providing 3 g lipid, 15 g glucose, and 3 g amino acids kg(-1) x d(-1) and underwent 1) indirect calorimetry and 2) a primed, 2-h infusion of H13CO3Na to assess the recovery of 13C in breath, immediately followed by 3) a 3-h infusion of L-[1-13C]leucine. RESULTS: The respiratory quotient tended to be slightly but not significantly higher in the mixed MCT than in the LCT group (0.96+/-0.06 compared with 0.93+/-0.03). We did not detect a significant difference between the mixed MCT and LCT groups with regard to release of leucine from protein breakdown (B; 309+/-40 compared with 257+/-46 micromol x kg(-1) x h(-1)) and nonoxidative leucine disposal (NOLD; 296+/-36 compared with 285+/-49 micromol x kg(-1) x h(-1)). In contrast, leucine oxidation was greater in the mixed MCT than in the LCT group (113+/-10 compared with 67+/-10 micromol x kg(-1) x h(-1); P = 0.007). Net leucine balance (NOLD - B) was less positive in the mixed MCT than in the LCT group (-14+/-9 compared with 28+/-10 micromol x kg(-1) x h(-1); P = 0.011). CONCLUSION: Mixed MCTs may not be as effective as LCT-containing emulsions in promoting protein accretion in parenterally fed preterm neonates.

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Abstract: Renal venous thrombosis (RVT) is a rare event in neonates and infants. Its incidence varies from 0.5 per thousand concerning admissions in neonatal intensive care units to 0.5% in autopsic findings. Some cases may occur in the antenatal period. Clinical presentation in infants includes a mass in the flank. hematuria and thrombocytopenia. We report a case of RVT which was diagnosed at 34 weeks' gestation by ultrasound in a fetus showing cardiotocographic signs of fetal distress. We observed the typical pattern reported by pediatric radiologists: renal enlargement, loss of the cortico-medullary boundary, echoic streaks following the direction of interlobular veins, lack of definition of renal sinus echoes and loss of venous flow in the right kidney by Doppler velocimetry. After delivery by caesarean section and transient hyperbilirubinemia and moderately impaired renal function the infant weighing 2435 g had a full recovery at 1 week and a normal evolution at 1 month of life.

Abstract: The aim of this study was to determine interobserver variation in Doppler assessment of mean left pulmonary arterial flow velocity, and its normal values during the first 24h of life. The interobserver variation was determined by a Bland and Altman analysis of the values of mean velocity measured in 21 newborns by 2 observers. Then, normal values of mean velocity were measured in 15 newborns at 5, 10 and 15 min of life in the delivery room, and in 14 other newborns at 1, 2, 6, 12 and 24h of life in the nursery unit. The interobserver variation was found to be acceptable. Mean velocity had a few variations within the first 24 h, but remained consistently above 20 cm s(-1). In conclusion, mean velocity values below 20 cm(-1) suggest low pulmonary blood flow.

Abstract: AIMS: Since vancomycin's bactericidal action has been shown to be time-dependent, a constant rate infusion over 24 h might result in a better bactericidal efficacy. The purpose of this study was to define a new dosage schedule in prematures. METHODS: Two vancomycin 24 h constant rate infusion schedules were tested in two groups of neonates. Postconceptional age (PCA) was 27 to 41 weeks in group 1 (n=24) and 28 to 51.5 weeks in group 2 (n=29). Group 1 neonates received continuous infusion of 10 to 30 mgkg(-1) day(-1), adjusted for PCA and weight. Group 2 was designed to take into account the significant relationship observed in group 1 between vancomycin clearance standardized on weight and PCA and consisted of a constant loading dose of 7 mg kg(-1) followed by continuous infusion of 10 to 40 mg kg(-1) day(-1) adjusted for PCA and weight. RESULTS: Mean vancomycin serum concentration at steady state was 11+/-3.1 mg1(-1) in group 1 and 15.4+/-6.2 mg1(-1) in group 2. Fifty-six percent of group 1 values vs 88% of group 2 values were between 10 and 30 mg at steady state (P<0.01). Both regimens were well tolerated. CONCLUSIONS: A loading dose of vancomycin followed by constant rate infusion of the appropriate dose adjusted for PCA and weight might improve vancomycin concentrations in neonates.

Abstract: Persisting spongy myocardium (also known as noncompaction of the ventricular myocardium) is a rare and special form of cardiomyopathy. The few cases reported in the literature were detected postnatally and involved a high rate of cardiovascular complications. This anomaly of endomyocardial morphogenesis, which occurs during the embryonic phase at the stage of cardiac partitioning, is characterised by an excessive number of prominent trabeculae and by intertrabecular recesses within the myocardial wall. Antenatal detection is difficult in the absence of an associated malformation, which is the general situation. We report a case of antenatal cardiomyopathy which led to therapeutic abortion. The diagnosis of persisting spongy myocardium was made during fetopathologic examination.

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Abstract: BACKGROUND: Refractory hypoxemia in the newborn requires a precise diagnostic investigation for optimal and fast management. CASE REPORT: A full term newborn presented with refractory hypoxemia associated with radiologically clear lung fields and extrapulmonary shunt. Echocardiography ruled out a cardiac malformation. The persistence of hypoxemia despite treatment of the extrapulmonary shunt and the absence of parenchymatous pulmonary disease led to suspect misaligned lung vessels with alveolar capillary dysplasia. This diagnosis was confirmed by post mortem microscopic examination of the lung. CONCLUSION: The diagnosis of misaligned lung vessels with alveolar capillary dysplasia can be suspected on clinical features. The disposition of pulmonary veins must be checked to recognize this disease in case of neonatal death with pulmonary hypertension.

Abstract: Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10-80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51+/-21 vs 23+/-17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45+/-20 vs 20+/-17, P < .0001), 'idiopathic' PPHN (39+/-14 vs 14+/-9, P < .0001), and sepsis (55+/-25 vs 26+/-20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI=41+/-16 vs 28+/-18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI=58+/-25 vs 46+/-32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age > or =34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants.

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Abstract: AIMS: To determine whether it is possible to assess baroreflex sensitivity in neonates by studying only spontaneous variation in systolic blood pressure and heart rate. METHODS: ECG and non-invasive blood pressure signals were continuously studied in 14 preterm neonates (term 29-32 weeks) and five term neonates (term 40-41 weeks). Non-invasive blood pressure measures were obtained using a Finapres placed around the child's wrist. Both signals (ECG and blood pressure), sampled at 400 Hz, were digitised by an A/D converter and stored in a binary mode on magnetic disk. An inhouse software QRS detection algorithm was used to define R peaks of the QRS complexes with an accuracy greater than 2 ms. Four 4 minute periods were recorded in each infant. The slope of the linear regression of RR intervals versus systolic blood pressure was calculated in each period and the mean value of the four slopes was then considered as the index of baroreflex sensitivity (in ms/mm Hg) in each neonate. RESULTS: Spontaneous baroreflex sensitivity was lower in preterm neonates than in term neonates (mean(SD): 4.07 (2.19) ms/mm Hg vs 10.23 (2.92) ms/mm Hg). CONCLUSION: Baroreflex sensitivity can be assessed in term and preterm neonates by studying spontaneous variations in systolic blood pressure alone. This method could be useful for studying the ontogeny of baroreflex sensitivity and might therefore provide information about the maturation of the autonomic nervous system.

Abstract: The feasibility of using a Finapres device to reproduce the beat to beat signal of arterial blood pressure in eight neonates was assessed and compared with intra-arterial measurement of arterial blood pressure in the umbilical artery, using a catheter. The two methods gave similar results. Continuous recording of arterial blood pressure in neonates using Finapres is feasible and reliable.

Abstract: Newborn infants may have a high oxygen cost of breathing (OCB) at the time of being weaned from mechanical ventilation. We hypothesized that this increase in oxygen consumption (V'O2) could be reduced by using certain weaning ventilatory modes. We designed a study to assess V'O2 during three weaning ventilatory modes: patient triggered ventilation, synchronous intermittent mandatory ventilation (SIMV) and continuous positive airway pressure in 16 newborn infants before being weaned from mechanical ventilation In seven infants whose OCB was high. V'O2 was not significantly different between CV and PTV (8.9+/-0.6 versus 9.5+/-0.8, respectively) whereas it tended to increase to 10.8+/-1.1 mL x min(-1) x kg(-1) during SIMV and increased significantly to 11.9+/-0.8 mL x min(-1) x kg(-1). In the other nine infants whose OCB was normal, no significant variation of V'O2 was observed. Patient triggered ventilation was a weaning ventilatory mode that significantly reduced the increase in oxygen consumption observed in infants with a high oxygen cost of breathing, as compared to synchronous intermittent mandatory ventilation or continuous positive airway pressure. Further investigations in newborn infants with a high oxygen cost of breathing should be performed prior to routine use of patient triggered ventilation.

Abstract: BACKGROUND: Acute respiratory distress occurring in a child without any past medical history can have different origins. Pulmonary edema can be lesional or hemodynamic in origin. Bronchoalveolar lavage often allows indication of the type of lesional oedema. CASE REPORT: A 13-year old child was hospitalized for acute respiratory distress 24 hours after knee surgery complicated by a fracture of the tibial metaphysis. There were no clinical manifestations of airway obstruction. Chest X-ray showed pulmonary parenchymous pathology. Pulmonary edema secondary to congestive heart failure was eliminated by doppler echocardiogram. The cause of lesional pulmonary edema was found with bronchoalveolar lavage that showed fat drops in the cytoplasm of many alveolar macrophages. CONCLUSION: Fat embolism syndrome may be confirmed by examination of bronchoalveolar lavage fluid.

Abstract: Periventricular leukomalacia is an infrequent but severe lesion in the premature neonate. The presence of positive rolandic sharp waves (PRSW) on the electroencephalogram, regardless of their morphology, is a reliable marker of periventricular ischemia, justifying systematic EEG monitoring during the first three weeks of life for infants born at less than 34 weeks of amenorrhea. A retrospective study of 32 premature neonates with extensive cavitary periventricular leukomalacia confirmed the early occurrence of positive rolandic sharp waves in 84% of premature newborns. The mean rate of PRSW was 1.54/min, but showed great variability. In C(Z), these sharp waves which were more frequent or isolated in one case, had the same value as those recorded in C3 or C4. Four neonates had no PRSW, but late periventricular leukomalacia was diagnosed at one month of age. As all these premature infants were born before 29 weeks of amenorrhea, longer EEG monitoring was justified. The prognosis was very poor: 17 newborns died, 11 had motor, sensory and intellectual impairment, and three had motor lesions.

Abstract: In order to assess the perinatal health policy in a French department in comparison with other policies, we performed a prospective transversal survey in the Loire-Atlantique for 5 weeks. Newborns were registered according to clinical data using the Paris pediatricians classification (classes 1 to 4) and maternity wards by number of health personnel and facilities using the American Academy of Pediatrician classification (I-III). 1316 newborns were registered. This survey showed that the health care organization in maternity wards is rational in the Loire-Atlantique for newborns in classes 1 and 4. However, care for newborns in classes 2 and 3 could be provided in maternity wards in classes II and III if available personnel and equipment is improved.

Abstract: Oxygen consumption (VO2) was measured during controlled and spontaneous ventilation with continuous positive airway pressure in newborn infants in whom chronic lung disease later developed. The oxygen cost of breathing (the difference in VO2 between spontaneous and controlled ventilation) was significantly higher in infants with chronic lung disease than in control infants (20.1% +/- 7.5% and 4.8% +/- 4.9% of VO2 during spontaneous ventilation (p < 0.05), respectively).

Abstract: Measurements of oxygen uptake (VO2) and CO2 output (VCO2) are useful in critically ill patients. However, VO2 is not routinely measured in intensive care during mechanical ventilation (MV) especially in premature newborns. The present study describes a new method of measuring VO2 and VCO2 using a double open circuit which accounts for gas leaks around the uncuffed tracheal tube. The accuracy of the method was assessed with N2 and CO2 infusion. In case of leaks, VO2 and VCO2 measurement was significantly underestimated by the simple circuit method. This underestimation was not present with double circuit method. Five preterm newborns were studied. VO2 and VCO2 using the double open circuit were compared with the classic simple circuit. During MV, the mean underestimation assessed by the difference between simple and double circuit measurement was -12% (range from 0 to -29%) for VO2 and -14% (range 0 to -26%) for VCO2.

Abstract: Nitric oxide inhalation can benefit newborn babies with right-to-left extrapulmonary shunt (EPS). Using doppler ultrasound, we compared the effects of nitric oxide on systemic oxygenation and mean pulmonary-blood-flow velocity (MPBFV) in severely hypoxic babies with or without EPS. With a median (interquartile range) dose of 20 (32) parts per million, oxygenation index decreased significantly in both groups (EPS, 49 [19] vs 11 [9]; non-EPS, 40 [11] vs 20 [13]). The decrease was significantly greater in the EPS group. MPBFV increased significantly in the EPS group (18 [4] vs 29 [8] m/s) only. Nitric oxide may improve systemic oxygenation in neonates with severe hypoxaemia secondary to EPS by increasing pulmonary blood flow, and in those without EPS by improving ventilation-perfusion matching.

Abstract: We developed two multidisciplinary tutorial programs (TOBRA-DIDACT and VANCO-DIDACT) for teaching the basic principles of antibiotic drug monitoring by simulation of repeated administrations to fictitious patients whose physio-pathologic characteristics were pre-defined in the programs. To illustrate the two types of bactericidal kinetics, we have chosen one time-dependent (vancomycin) and one concentration-dependent (tobramycin) antibiotic. These computer-assisted programs operate on an interactive mode. In each of them, three main steps are connected: (1) Various types of clinical cases are submitted to the student: for each of them, case report includes clinical characteristics, location of infection, bacterial strain and minimal bactericidal concentration. These data must be taken into account during the following steps. (2) The student has to establish the treatment schedule: route of administration, dose for each injection, intervals between injections and duration of infusion. (3) The result of the dosage scheme proposed by the student is represented by a simulation of plotting antibiotic plasma concentrations vs. time during the first 4 days of treatment. These curves are obtained by a monoexponential (TOBRA-DIDACT) or biexponential (VANCO-DIDACT) pharmacokinetic model. Peak and trough concentrations are calculated at steady-state. An expert system provides a commentary with each result to evaluate the efficacy of the treatment and to assist the student in improving his prescription. TOBRA-DIDACT and VANCO-DIDACT illustrate the influence of age, obesity, renal impairment, location of infection and bacterial strain on antibiotic therapy. They also show the role of route of administration, dosing and intervals between injections on therapeutic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: A randomised double blind study was designed to evaluate haemodynamic response to dobutamine and dopamine in 20 hypotensive preterm infants of less than 32 weeks' gestation. Neonates initially received dopamine or dobutamine 5 micrograms/kg/min. If mean arterial pressure (MAP) remained below 31 mm Hg, the infusion rate was increased in increments of 5 micrograms/kg/min. If 20 micrograms/kg/min of the initial drug failed to achieve a MAP above 30 mm Hg, it was discontinued and the other drug was administered at the same infusion rate. Left ventricular output (LVO) was measured by pulsed Doppler echocardiography. Mean (SE) MAP increased significantly from 24.4 (1.0) to 32.0 (1.4) mm Hg at a median dobutamine dosage of 20 micrograms/kg/min and from 25.6 (1.2) to 37.7 (1.5) mm Hg at a median dopamine dosage of 12.5 micrograms/kg/min. The percentage LVO increase was +21 (7)% with dobutamine compared with -14 (8)% with dopamine. Dobutamine failed to increase MAP above 30 mm Hg in six infants out of 10, whereas dopamine succeeded in all 10 infants. Six switches from dobutamine to dopamine were thus performed, providing a rise in MAP (29.2 (0.5) to 41.2 (2.0) mm Hg) and drop in LVO (356 (40) to 263 (36) ml/kg/min). These data indicate that dopamine is more effective than dobutamine in raising and maintaining MAP above 30 mm Hg; however dopamine does not increase LVO.

Abstract: Despite advances in therapy for maternal diabetes, pregnancies of diabetic women remained at an increased risk of spontaneous abortion or delivery of an infant with major malformation. We report on an infant of a diabetic mother with hypoglossia-hypodactylia associated with complete jejunal atresia. A common pathogenesis for these 2 malformations could be a vascular disruptive mechanism with in utero arterial thrombosis.

Abstract: BACKGROUND. Cardiac metastases from malignant tumors are rare in children and are usually found only at necropsy. CASE REPORT. A girl aged 6 months developed a swelling in the area of her left shoulder. Surgical excision was incomplete and pathological examination indicated neuroectodermic soft-tissue tumor. Chemotherapy with cyclophosphamide, doxorubicin then vincristine and actinomycin D was instituted, followed by second course of cyclophosphamide-doxorubicin. Three months after cessation of chemotherapy, the child developed manifestations of congestive cardiac failure that could not be induced by anthracycline (total cumulative dose: 275 mg/m2). Cardiac ultrasonography showed a metastatic tumor (diam = 3 cm) on the wall of the right ventricle and atrium, which was pedunculated inside the infundibular chamber. It was partly excised, and the patient was treated with etoposide and carboplatin. But a second metastatic tumor formed in the paravertebral area. CONCLUSION. This is the first description, to our knowledge, of cardiac metastases from neuroectodermic tumor. They were diagnosed by cardiac ultrasonography, as this imaging technique differentiates this complication from the anthracycline-induced cardiomyopathy usually seen in children developing cardiac failure under chemotherapy.

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Abstract: A survey was undertaken in 3 French departments of the Pays de Loire from January 1, 1986 to December 31, 1986. Among the 32,876 neonate (NN) population, the authors studied the 2,753 NN who were hospitalized and a control group of 1,458 NN representative of the population of 30,123 NN who were not hospitalized. Socioeconomic patterns of mothers, of their pregnancies and deliveries were studied in both groups. The control group was compared with the data obtained in 1981 at the national level and in 1982 at the local level. This group was used as a reference for the study of hospitalized NN. Intrauterine growth retardation rate was 2.4%, prematurity rate 4.6% of live births, very premature rate (as defined by a gestational age less than 32 weeks) was 0.45% of births. Among the group of hospitalized NN, which represent 8.5% of the general population, the NN were regrouped according to Cullen's classification and their care load estimated according to the Omega score. Thus 2 subgroups were defined: the 2,298 ordinarily hospitalized (Cullen's classes I and II) and the 455 severely sick NN (classes III and IV) i.e. 1.3% of births. One third of the severely ill NN were very prematures. The 2 other thirds presented with respiratory (24%), infectious (24%), malformative (19%) or neurological (13%) diseases. Lengths of stay and Omega scores varied according to the causes for hospitalizations and were inversely correlated with gestational ages (p less than 0.001). Neonatal mortality was 3.3 p. 1,000 births and rate of stillbirths 6.5 p. 1,000.

Abstract: The precise diagnosis of lower respiratory tract infection in the critically ill newborn remains a difficult challenge. The bronchoscopic protected specimen brush (PSB) is a reliable method in intubated adults. Because the bronchoscopic procedure is not generally available for young children, Zucker proposed a blind technique for introducing the PSB into the distal airways. His results were promising but were not compared with any bacteriologic reference method. Therefore, we wanted to evaluate this technique in comparison with the open lung biopsy (OLB) when it could be ethically accomplished. Eleven PSB were collected simultaneously with an OLB. The sensitivity of the PSB procedure was 100%, its specificity 88%, its positive predictive value 66%, and its negative predictive value 100%. There were no complications secondary to the PSB procedure. In this short study, the PSB procedure using a blind technique is safe and feasible to obtain uncontaminated specimens in intubated and ventilated newborns, and is largely accurate in identifying the bacterial etiologic agent of lower respiratory tract infection.

Abstract: Two consecutive studies of amikacin plasma levels were performed in 63 and 64 neonates whose postconceptional age (PCA) ranged from 26 to 45 weeks. The first study, using a dose of 7.5 mg/kg every 12 hours, permitted to establish a dosage related to PCA. Half-life elimination of amikacin was strongly correlated with PCA (r = -0.42, p = 0.0009). The apparent volume of distribution was correlated with none of the variables studied. The mean volume of distribution was 640 +/- 190 ml/kg. From these data, the inferred dosage was 10 mg/kg, given at intervals of time predetermined as a function of PCA. A second prospective study proved the value of this PCA adapted dosage. The maximal concentrations obtained were higher (21.6 +/- 5.9 vs 18.5 +/- 4.6 micrograms/ml, p less than 0.001), the nadir concentrations were not significantly increased (5.7 +/- 3.1 vs 5.2 +/- 3.7 micrograms/ml, NS) and the number of nadir concentrations outside the desired interval of 2-8 micrograms/ml was smaller (p less than 0.01).

Abstract: Most cephalhematomas resorb spontaneously; intervention by means of needle aspiration may introduce infection. In our case, a neonatal septicemia was associated with a large parietal cephalhematoma. The newborn was discharged after treatment of sepsis. Three days later, the diagnosis of infected cephalhematoma was apparent, associated with meningitis and septicemia. The authors discuss the physiopathology of the infection, antimicrobial therapy and careful aspiration when a serious infection is associated with cephalhematoma.

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Abstract: Rapid bactericidal effect is essential for therapy of severe Staphylococcus aureus infections in children. The in vitro activity of clinically achievable levels of vancomycin and its combinations with gentamicin, amikacin and rifampin plus amikacin was studied with the time-kill curve method at 2.5, 4, 6, 24 and 48 hours against 20 strains of Staphylococcus aureus isolated from children with severe staphylococcal infection. Vancomycin alone exerted a bactericidal effect at 48 hours. However, with the combinations vancomycin plus gentamicin, vancomycin plus amikacin and vancomycin plus amikacin plus rifampin a bactericidal effect was respectively observed at 24, 6 and 4 hours. Most rapid killing was achieved with vancomycin plus rifampin plus amikacin. Thus this antibiotic combination seems the most appropriate for initial treatment of severe staphylococcal infections in children.

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Abstract: There are no reports analyzing the results of pediatric intensive care in Europe. We evaluated quantitatively the severity of illness and the amount of care required for 714 consecutively admitted patients. We used simultaneously the Clinical Classification System (CCS) the Acute Physiology Score (APS) and the Therapeutic Intervention Scoring System (TISS). Overall mortality at 1 month was 15%. The mortality rate was higher for CCS Class IV patients (32.3%) than for CCS III (4.5%) and CCS II (3.2%). The difference was significant between CCS IV and CCS III and II respectively (p less than 0.001) but no difference was observed between CCS III and CCS II. The patients were also classified among 7 major organ system failures: cardio vascular, respiratory, neurologic, gastro intestinal, renal, metabolic, hematologic. Three of them were primarily involved: respiratory (44.9%) cardio-vascular (20.7%), neurologic (18.8%). Among these 3 groups the highest mortality was observed in cardio-vascular patients (p less than 0.01 v.s. respiratory, p less than 0.05 v.s. neurologic). The death rate was 22% among the 264 neonates, 9.7% among the 247 infants (p less than 0.01) and 12.6% among the 198 children. APS and TISS scores increased significantly with the CCS classes.(ABSTRACT TRUNCATED AT 250 WORDS)

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Abstract: A retrospective national study undertaken by the Club Français de Réanimation Pédiatrique found 103 children hospitalized in intensive care units for severe infectious purpura in 1984, i.e. 1.08 case per department. A great heterogeneity in the geographic distribution was observed. The responsible agent was identified in 65% of cases. Short-term evolution was severe: death in 48%.

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Abstract: The prognosis of hemolytic uremic syndrome was studied in 37 children hospitalized between January 1980 and January 1985. 75% of affected children were less than 3 years of age. Twenty-two (60%) presented with anuria or oliguria (mean duration of anuria: 10.7 days). In this last group, severe extrarenal manifestations occurred: 12 cases of neurological involvement (6 involving hypervolemia), gastrointestinal involvement in 5 cases, including a case of ileal necrosis; pancreatic involvement in another. Three children died during the first month of the disease (overall death-rate: 8%). Thirty-two children were followed with a mean 24 months follow-up (6 months to 60 months). Six (19%) presented with sequellae, of which 3 were severe: one severe arterial hypertension and two with chronic renal failure of which one terminal with severe neurologic sequellae. The existence of extrarenal manifestations implies a poor prognosis. Among the 22 children with anuria or oliguria, 8 had no extra-renal manifestations. All of these recovered. Three of 11 children with one extrarenal manifestation had an unfavorable outcome. The course was unfavorable in the 3 cases with multiple extrarenal involvement.

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