[Prenatal diagnosis of congenital mesoblastic nephroma. A case report]. / Diagnostic anténatal d'un néphrome mésoblastique congénital.

UNLABELLED: Antenatal ultrasounds allow the detection of renal tumors, especially renal mesoblastic nephromas, but only the pathological analysis of the surgical specimen can confirm this diagnosis postnatally. OBSERVATION: We report the prenatal discovery of a mesoblastic nephroma because of premature labour. Postnatal early surgery was decided because of possible complications in this premature infant. Histology revealed mesoblastic nephroma. COMMENTS: We point out the diagnostic elements of congenital mesoblastic nephroma, especially in what is related to arterial hypertension and hypercalcemia, histology and cytogenetics.

Benefit of antenatal glucocorticoids according to the cause of very premature birth.

In this observational study performed in a large cohort of very preterm singletons, respiratory outcome was found to be strongly dependent on the cause of premature delivery. Although less apparent in infants born to mothers with chorioamnionitis, exposure to antenatal glucocorticoids remained significantly associated with a decrease in the incidence of respiratory distress syndrome after adjustment for the main cause of premature birth.

Lower respiratory tract illness and RSV prophylaxis in very premature infants.

AIMS: To determine the frequency of and the risk factors for readmissions for any lower respiratory tract illness (LRTI) and for respiratory syncytial virus (RSV) documented LRTI in children born very prematurely who had or had not received RSV prophylaxis. METHODS: Multicentre prospective longitudinal cohort study of 2813 infants, born between April 2000 and December 2000 at less than 33 weeks of gestational age, and followed until the end of the epidemic season. RESULTS: Among the 2256 children who had no bronchopulmonary dysplasia at 36 weeks of postmenstrual age and were not submitted to RSV prophylaxis, 27.4% were readmitted at least once for any reason during the epidemic season; 15.1% and 7.2% were readmitted at least once for any LRTI and RSV related LRTI, respectively. Children born at less than 31 weeks' gestation, having an intrauterine growth restriction, or living in a single mother family were at a significantly higher risk of readmission for LRTI in general as well as for RSV related LRTI. Of the 376 children submitted to prophylaxis, 28.2% were readmitted at least once for any LRTI and 6.1% for RSV related LRTI. CONCLUSION: One out of four children who had received no prophylaxis, was born very prematurely, and was without bronchopulmonary dysplasia at 36 weeks of postmenstrual age, was readmitted at least once for any reason. Roughly 50% and 20% of these readmissions were related to a LRTI and an RSV infection, respectively. Further epidemiological studies are warranted to assess the aetiology and impact of other respiratory pathogens on post-discharge readmission and respiratory morbidity in this population.

A model of pulmonary adenocarcinoma in transgenic mice expressing the simian virus 40 T antigen driven by the rat Calbindin-D9K (CaBP9K) promoter.

Lung cancer is the most frequent cause of cancer deaths. Its origin and development remain poorly understood, partly because of the lack of pertinent animal models. This study produced transgenic mice expressing the simian virus (SV) 40 T antigen (Tag) driven by a 1011 base-pair DNA fragment of the rat Calbindin-D9K (CaBP9K) promoter. All transgenic animals developed multifocal pulmonary tumours with pathological and ultrastructural features consistent with adenocarcinomas. Using immunohistochemistry, northern blot or western blot, tumours were found to express the transcription factor TTF-1, as well as specific markers of the peripheral airway Clara cells (CC10) and alveolar type II cells (surfactant proteins A, B, C, and D). This model, with its similarities to human adenocarcinoma, should be useful not only for addressing the mechanisms underlying the development and progression of lung cancer, but also for testing new therapeutic approaches.

Late-onset cystic periventricular leukomalacia in premature infants: a threat until term.

The purposes of this study are (1) to describe a "late-onset" form of cystic periventricular leukomalacia eventually appearing in premature infants whose neurological assessments were normal in the first month of life; (2) to retrospectively evaluate its incidence among a large population of premature infants; (3) to suggest that a few unexpected complications of prematurity may trigger the development of white matter damage, even several weeks after birth. Retrospective study in a population of 1452 surviving infants after 5 days born before 33 weeks. We identified 10 cases of late-onset cystic periventricular leukomalacia appearing beyond the first 5 weeks of life. In 8 cases, an intercurrent event associated with a systemic inflammatory response preceded the appearance of cysts: necrotizing enterocolitis (n = 5), septicemia (n = 2 cases), strangulated inguinal hernia in one infant. Neurological surveillance should be repeated until discharge in very preterm infants, especially after the occurrence of an intercurrent complication coming along with a systemic inflammatory response.

Treatment of post-haemorrhage ventricular dilatation with an Ommaya's reservoir: management and outcome of 64 preterm infants.

Over a 5-year period, an Ommaya's reservoir has been inserted in a single neurosurgical centre in each of 64 preterm infants with post-haemorrhage ventricular dilatation (PHVD). Their mean gestational age at birth was 29.2 weeks. The average age at reservoir insertion was 24 days. Seventeen infants received a fibrinolytic agent through the reservoir. Infections occurred in 14 patients. Two patients died after handling of their reservoirs. Thirty-one of the 45 survivors required a shunt placement. After a follow-up ranging from 6 months to more than 4 years, 17 of 43 patients have severe sequelae or are handicapped. Compared with the results of other studies, our experience does not suggest that treatment of PHVD with an Ommaya's reservoir is beneficial in term of mortality, shunt placement, and/or neurological outcome. The place of Ommaya's reservoir among the various means of managing PHVD should be carefully evaluated, as should the best way of using this appliance safely.

[Effect of perinatal inflammation syndrome on lung maturation and development]. / Conséquences sur la maturation et le développement pulmonaires du syndrome inflammatoire périnatal.

Despite improvement in neonatal care, the incidence of bronchopulmonary dysplasia has not decreased over the last decade. Moreover, chronic lung disease still occurs in very premature infants who do not require ventilatory support at birth. This review presents the growing body of epidemiological, experimental and clinical evidence suggesting that the occurrence of an inflammatory reaction triggered in utero or immediately after birth is associated with the subsequent development of chronic lung disease. However, stimulators of inflammation or specific proinflammatory cytokines may also have beneficial on lung maturation. How proinflammatory mediators interfere with lung maturation and alveolarization needs to be better understood in order to pave the way for new immunomodulatory strategies to prevent chronic lung disease in very preterm infants.

Prospective randomized multicenter comparison of high-frequency oscillatory ventilation and conventional ventilation in preterm infants of less than 30 weeks with respiratory distress syndrome.

BACKGROUND: Early use of high-frequency ventilation and exogenous surfactant is proposed as the optimal mode of ventilatory support in infants with respiratory distress syndrome. In very premature infants, we tested the hypothesis that high-frequency versus conventional ventilation could decrease exogenous surfactant requirements and improve pulmonary outcome, without altering the complication rate, including that of severe intraventricular hemorrhage. METHODS: Preterm infants with a postmenstrual age of 24 to 29 weeks, presenting with respiratory distress syndrome were randomly assigned to high-frequency oscillatory ventilation (lung volume recruitment strategy) or conventional ventilation. RESULTS: Two hundred seventy-three infants were enrolled. One hundred fifty-three had a postmenstrual age of 24 to 27 weeks, and 143 had a birth weight /=2 instillations of exogenous surfactant (30% vs 62%; odds ratio:.27; 95% confidence interval:.16-.44) and no difference in pulmonary outcome. The incidence of severe intraventricular hemorrhage was 24% in the high-frequency group and 14% in the conventional ventilation group (adjusted odds ratio: 1.50; 95% confidence interval:.68-3.30). CONCLUSION: Early use of high-frequency oscillatory ventilation in very premature infants decreases exogenous surfactant requirements, does not improve the pulmonary outcome, and may be associated with an increased incidence of severe intraventricular hemorrhage.

Methylprednisolone, an alternative to dexamethasone in very premature infants at risk of chronic lung disease.

OBJECTIVE: To evaluate the benefits and the medium-term side effects of methylprednisolone in very preterm infants at risk of chronic lung disease. STUDY DESIGN: Forty-five consecutive preterm infants (< 30 weeks' gestation) at risk of chronic lung disease were treated at a mean postnatal age of 16 days with a tapering course of methylprednisolone. The outcome of treatment was assessed by comparison with 45 consecutive historical cases of infants treated with dexamethasone; the infants did not differ in baseline characteristics. RESULTS: There were no differences between groups in the rate of survivors without chronic lung disease. Infants treated with methylprednisolone had a higher rate of body weight gain during the treatment period (median 120 g, range 0 to 190, vs. 70 g, range -110 to 210, P = 0.01) and between birth and the age of 40 weeks (median 1660 g, range 1170-2520, vs. 1580 g, range 1,040 to 2,120, P = 0.02). The incidence of both glucose intolerance requiring insulin (0 % vs. 18 %, P = 0.006) and cystic periventricular leukomalacia (2 % vs. 18%, P = 0.03) was lower among methylprednisolone-treated infants. CONCLUSION: Our observations confirm methylprednisolone to be as effective as dexamethasone and to have fewer side effects. A randomized control trial is needed to further study the efficacy and safety of methylprednisolone in very premature infants at risk of chronic lung disease.

Multiple courses of antenatal glucocorticoid treatment and fetal outcome.

Thanks to the US National Institutes of Health Consensus Conference, the odds of antenatal use of glucocorticoids for preventing severe neonatal complications of premature delivery have significantly increased these last years. The belief that neonatal benefits last up to 7 days after the first course and administration of further courses is safe has led many obstetricians to prescribe multiple antenatal glucocorticoid courses. Whether multiple courses offer an advantage over a single course has not been demonstrated. In contrast, there are accumulating evidence suggesting that this practice may have short and long-term side effects. The potential benefits and side effects of multiple antenatal courses of glucocorticoids, extrapolated from experimental data and observational studies, are detailed in this review. Until the results of ongoing randomized trials with long term follow-up are available, the practice of giving multiple courses of glucocorticoids to women should be considered with the greatest caution.

The relationships between antenatal management, the cause of delivery and neonatal outcome in a large cohort of very preterm singleton infants.

OBJECTIVE: To determine whether the cause of very preterm delivery influences neonatal outcome. DESIGN: A cohort study of 685 consecutive singletons born before 33 weeks of gestation. METHODS: Causes of birth and perinatal outcome variables were correlated for statistical significance by uni- and multi-variate analyses. RESULTS: Intrauterine growth retardation or pre-eclampsia were associated with a higher rate of respiratory distress syndrome compared with prolonged rupture of membranes, after controlling for gestational age, antenatal corticosteroid therapy, antenatal antibiotic administration, mode of delivery and origin (inborn or outborn) (adjusted OR 3.12; 95% CI 1.55-6.28). The prevalence of grade 3-4 intraventricular haemorrhage or cystic periventricular leukomalacia was 25% in newborn babies born after intrauterine infection or prolonged rupture of membranes. Among infants born after intrauterine growth retardation/pre-eclampsia, the rate of severe intraventricular haemorrhage was 3.2% and the rate of periventricular leukomalacia was 0.9%. Compared with intrauterine infection and after controlling for potential confounding covariates, intrauterine growth retardation/pre-eclampsia was associated with a lower rate of periventricular leukomalacia (adjusted OR 0.08; 95% CI 0.02-0.41). In the same multiple logistic regression model, antenatal corticosteroid administration was associated with a lower incidence of periventricular leukomalacia (adjusted OR 0.36; 95% CI 0.16-0.79). CONCLUSIONS: The cause of very preterm delivery has an important influence on neonatal outcome.

[Constitutional deficiency of pulmonary surfactant protein B: clinical presentation, histologic and molecular diagnosis]. / Déficit constitutionnel en protéine B du surfactant pulmonaire: présentation clinique, diagnostic histologique et moléculaire.

We report a female full-term infant with fatal respiratory failure of early onset due to inherited SP-B deficiency. Lung biopsy was performed at 18 days after birth, with histopathological characterization indicating congenital alveolar proteinosis. Immunohistochemical studies of lung tissue revealed the absence of SP-B and the presence of intra-alveolar SP-A normal quantities. Analysis of genomic DNA showed homozygosity for the 121ins2 mutation of the SFTPB gene. The infant died 21 days after birth. Both parents were heterozygotes for the mutation. Chorionic villus sampling was performed at the first trimester of the following pregnancy. Restriction analysis of amplified fetal DNA, studies of microsatellite segregation and direct sequencing led to the diagnosis of homozygosity for the parental wild-type allele. The diagnosis of congenital SP-B deficiency should be suspected whenever an early and acute respiratory failure in a term or near-term infant does not resolve after five days of age: diagnostic confirmation can be easily and rapidly obtained with the analysis of genomic DNA and immunohistochemical characterization of lung tissue.

Outcome of premature infants delivered after prolonged premature rupture of membranes before 25 weeks of gestation.

OBJECTIVE: To identify factors influencing the outcome of premature infants delivered after prolonged premature rupture of membranes before 25 weeks' gestation. DESIGN AND POPULATION: All premature infants with gestational age <34 weeks, either inborn or outborn, with history of rupture of membranes before 25 weeks' gestation, admitted to our NICU between January 1992 and July 1997, were eligible for this retrospective study. Collected information included birth weight, gestational age at rupture of membranes and at delivery, duration between rupture of membranes and delivery (latency period), severity of oligohydramnios, pre- and post-natal managements, and follow-up of survivors. RESULTS: A total of 28 neonates fulfilled the inclusion criteria. Despite new strategies of ventilation and optimal management, the overall mortality rate was 43% (12/28). Nonsurvivors were significantly less mature at rupture of membranes, and had severe oligohydramnios (anamnios). We also noted less antenatal corticosteroids and antibiotic therapy in this group. Nine of eleven infants (82%) following rupture of membranes before 22 weeks' gestation died shortly after birth. The two remaining infants developed severe bronchopulmonary dysplasia. Nine deaths occurred in thirteen cases (69%) of anamnios. The major death causes were refractory respiratory failure and neurologic complications. Half of all survivors (8/16) developed bronchopulmonary dysplasia. CONCLUSION: The outcome of premature infants following prolonged premature rupture of membranes before 25 weeks' gestation is influenced by gestational age at rupture, severity of oligohydramnios, and antenatal antibiotics and corticosteroids. Neonates with rupture of membranes before 22 weeks have a very low chance of survival at the present time.

Maternal-fetal staphylococcal infections: a series report.

The objective of this paper is to study the characteristics of maternal-fetal staphyloccocal infection. A retrospective study among 1,582 infants admitted consecutively to our neonatal intensive care unit was carried out from January 1995 through September 1998. The antenatal history, and the clinical and bacteriological findings and outcome of the infants fulfilling maternal-fetal staphyloccocal infection were analysed. Among 122 (7.7%) maternal-fetal infection, 11 cases (8.9%) of congenital staphyloccal infections were diagnosed in 9 premature and 2 full-term babies. Antenatal invasive procedures were noted in 6 occasions (56%). All the 11 infants developed respiratory and hemodynamic failure. Staphylococcus aureus was the most common organism encountered in maternal bacteriologic data (9/11, 82%) as well as on peripheral sites (9/11, 82%) and in blood cultures (7/11, 64%) performed in the infants. There was one case of methicillin-resistant Staphylococcus aureus. The outcome was favorable for 9 infants. Two very preterm neonates died within the first 72 hours of life. Mother-to-infant transmission of Staphylococcus should be suspected whenever invasive procedures are performed during pregnancy and in the presence of severe neonatal distress associated with an inflammatory response. Prompt and adapted antibiotic therapy allows a favourable outcome.

Antenatal glucocorticoid treatment and cystic periventricular leukomalacia in very premature infants.

BACKGROUND: Antenatal glucocorticoid therapy decreases the incidence of several complications among very premature infants. However, its effect on the occurrence of cystic periventricular leukomalacia, a major cause of cerebral palsy, remains unknown. METHODS: We retrospectively analyzed a cohort of 883 live-born infants, with gestational ages ranging from 24 to 31 weeks, who were born between January 1993 and December 1996 at three perinatal centers in the Paris area. The mothers of 361 infants had received betamethasone before delivery, the mothers of 165 infants had received dexamethasone before delivery, and the mothers of 357 infants did not receive glucocorticoids. We compared the rates of cystic periventricular leukomalacia among the three groups of infants in bivariate and multivariate analyses after adjustment for confounding factors. RESULTS: The rate of cystic periventricular leukomalacia was 4.4 percent among the infants whose mothers had received betamethasone, 11.0 percent among the infants whose mothers had received dexamethasone, and 8.4 percent among the infants whose mothers had not received a glucocorticoid. After adjustment for gestational age, the mode of delivery, and the presence or absence of chorioamnionitis, prolonged interval between the rupture of membranes and delivery (>24 hours), preeclampsia, and the use of tocolytic drugs, antenatal exposure to betamethasone was associated with a lower risk of cystic periventricular leukomalacia than was either the absence of glucocorticoid therapy (adjusted odds ratio, 0.5; 95 percent confidence interval, 0.2 to 0.9) or exposure to dexamethasone (adjusted odds ratio, 0.3; 95 percent confidence interval, 0.1 to 0.7). The adjusted odds ratio for the group of infants whose mothers had received dexamethasone as compared with the group of infants whose mothers had not received a glucocorticoid was 1.5 (95 percent confidence interval, 0.8 to 2.9). CONCLUSIONS: Antenatal exposure to betamethasone but not dexamethasone is associated with a decreased risk of cystic periventricular leukomalacia among very premature infants.

Amniotic fluid concentrations of interleukin-1beta, interleukin-6 and TNF-alpha in chorioamnionitis before 32 weeks of gestation: histological associations and neonatal outcome.

OBJECTIVES: To test the association between cytokine levels in the amniotic fluid and (i) the vascular invasion phase of intrauterine infection, (ii) the occurrence of periventricular leukomalacia; to assess the correlation between C-reactive protein levels, a recognised biological marker of inflammation in maternal serum and cytokine levels in the amniotic fluid. DESIGN: Prospective clinical study. SETTING: Fetal medicine unit and neonatal intensive care unit, Antoine Beclere Hospital, Clamart, France. SAMPLE: Thirty-one pregnancies complicated by chorioamnionitis leading to birth before 32 weeks of gestation. METHODS: Interleukin 1-beta, Interleukin 6 and TNF-alpha prospectively measured in the amniotic fluid. Histological examination of the placenta. Ultrasound examination and magnetic resonance imaging of the brains of the newborn infants performed within the first week of life. MAIN OUTCOME MEASURES: The occurrence of periventricular leukomalacia was assessed by transfontanellar ultrasound and magnetic resonance imaging. RESULTS: There was a significant positive correlation between the occurrence of histological chorioamnionitis, vascular extension of infection of the membranes, maternal inflammatory syndrome and neonatal sepsis. A strong association was found between maternal serum C-reactive protein concentrations and cytokine levels in the amniotic fluid. Interleukin-1beta was the best predictor of vascular extension of chorioamnionitis, and TNF-alpha was the best predictor of the development of severe early neonatal infection. There was no association between the amniotic fluid levels of cytokines and the development of periventricular leukomalacia. CONCLUSIONS: These data suggest that IL-1beta, IL-6 and TNF-alpha are produced in relation to intrauterine inflammation and infection, but cannot be directly implicated in the development of fetal cerebral white matter lesions.