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.

[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.

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.

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.

[Prenatal corticotherapy and acceleration of fetal maturation. I. Experimental and pharmacological data]. / Corticothérapie anténatale et accélération de la maturation foetale. I. Données expérimentales et pharmacologiques.

Data from numerous experimental studies clearly indicate that endogenous corticosteroids physiologically act on the fetal lung maturation. There are also convincing experimental data demonstrating that exogenous corticosteroids stimulate phospholipids biosynthesis, induce the surfactant specific protein genes expression, and improve the lung biophysical properties. The first report of a clinical beneficial effect derived from these experimental observations is due to Liggins and Howie who demonstrated that prenatal corticosteroid treatment significantly reduces the incidence of respiratory distress syndrome and the mortality among preterm neonates. Fluorinated corticosteroids (dexamethasone, betamethasone) are the only efficient corticosteroids, with the advantage of a low mineralocorticoid activity. After a single course, they do not inhibit postnatal stress adrenal response; however, repeated courses may induce adrenal depression if a stressing event occurs after birth.

[Prenatal corticotherapy and acceleration of fetal maturation. II. Results of clinical applications]. / Corticothérapie anténatale et accélération de la maturation foetale. II. Résultats des applications cliniques.

Numerous subsequent controlled trials and recent meta-analysis have confirmed the efficiency of antenatal glucocorticoid therapy in reducing both the incidence of respiratory distress syndrome (RDS) and perinatal mortality. Moreover, antenatal glucocorticoid administration reduces the odds of several severe complications relating to immaturity: intraventricular hemorrhage (IVH), ductus arteriosus patency, necrotising enterocolitis, and hemodynamic failure. Exogenous surfactant therapy has not ruled out the benefits of corticosteroids: on the contrary, a synergic effect is obtained when both antenatal and postnatal therapeutic approaches are combined. Very premature infants may also take advantage of the hormonal treatment: in this population, RDS occurrence, IVH incidence and perinatal mortality are also reduced. Unfortunately, despite convincing evidence, the incidence of antenatal steroids therapy has not yet achieved the optimal and desirable level. Obstetricians and pediatricians must be encouraged to ensure high maternal exposure to steroids when preterm delivery is likely to occur.

[Surfactants in the digestive tube]. / Les surfactants dans le tube digestif.

Epithelia of the gastrointestinal tract both synthesize and secrete surfactant-like materials. Like the pulmonary surfactant, these materials contain not only phospholipids, but also surfactant apoproteins, regarded until recently as specific products of the bronchoalveolar epithelium. Presented here are the various roles, most of them still speculative, of these phospholipids-containing products in the gastro-intestinal tract.

[An unknown etiology of fetal ascites: acute intestinal intussusception]. / Une cause méconnue d'ascite foetal: l'invagination intestinale aiguë.

BACKGROUND: Intussusception is a frequent diagnosis during the first year of life. However, it is an uncommon and very rare pathology in neonates and premature infants. CASE REPORTS: Two full term neonates presented an antenatal intussusception associated with fetal ascites; another premature infant developed an intussusception at the age of 15 days. In the three cases the diagnosis of intussusception had only been established during the laparotomy. A recent review of the literature revealed 13 cases of antenatal intussusception, one of these being associated with fetal ascites. CONCLUSION: The differential diagnosis of fetal ascites should always include intussusception. Early recognition of this pathology and prompt surgical action would avoid fatalities.

[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.

[Maternofetal disseminated candidiasis and high-grade prematurity]. / Infection maternofoetale disséminée a Candida albicans et grande prématurite.

BACKGROUND: Despite the frequency of vaginal yeast colonization, serious candidiasis infections in pregnant patients or neonates remain rare. Four cases of disseminated congenital candidiasis in very preterm infants are reported. CASE REPORTS: Congenital Candida albicans infection has been diagnosed in four very preterm infants. In three cases, the mothers had intrauterine devices in place throughout pregnancy. A careful macroscopic examination of the umbilical cord and placenta after birth has allowed an early management strategy in three cases. In all cases, a serious infectious alveolitis occurred. A pronounced increase in white blood cells (> 50,000/mm3) and high levels of both segmented neutrophil and band cells, despite the frequent normality of the CRP, constituted other features. Infection was controlled by parenteral amphotericin B or fluconazole. In one case, serious thrombocytopenia occurred after the first amphotericin B injection requiring substitution for fluconazole. The outcome was unfavourable in two cases with an extensive periventricular leukomalacia. CONCLUSION: Congenital candidiasis in these four very preterm neonates has several features in common: intrauterine contraceptive device during pregnancy, characteristic chorioamnionitis and funisitis, high WBC count, infectious alveolitis. Fluconazole as alternative to amphotericine B therapy is proposed.

[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.

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.

Fetal rat lung type II cell differentiation in serum-free isolated cell culture: modulation and inhibition.

Undifferentiated fetal rat lung epithelial cells were isolated on gestational days 15 or 17 (term 22 days) and cultured in a defined medium. On plastic, most of the cells developed structurally abnormal lamellar bodies. On a basement membrane matrix (BMM), they sequentially accumulated glycogen and formed typical lamellar bodies. Biochemical analysis of the latter indicated that they had a phospholipid composition typical of surfactant for cells on BMM but not on plastic and that surfactant protein A appeared on BMM only. Progressing maturation from day 1 to day 6 in culture was demonstrated for 17-day cells on BMM by a sevenfold increase of labeled precursor incorporation into surfactant phospholipids. Exposure to medium conditioned by 21-day fetal fibroblasts enhanced incorporation already after a 1-day culture. The antisteroid RU 486 had no effect on differentiation, whereas transforming growth factor-beta, a factor produced by lung mesenchyme at early fetal stages, inhibited it markedly. Alveolar epithelial type II cells appear to be committed early, but their maturational process would be prevented until a definite gestational stage.

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.

Characterization of the rat pulmonary surfactant protein A promoter.

The expression of the pulmonary surfactant protein A (SP-A) is developmentally regulated and controlled by several hormones. In an attempt to characterize cis-acting elements involved in the regulation of SP-A expression, we have cloned the 5' flanking sequence of the rat SP-A gene. The promoter region contains a TATA box but no CAAT box. The transcription start site has been identified by anchored polymerase chain reaction and S1 nuclease mapping of the mature and precursor transcripts. S1 mapping of precursor transcripts has confirmed the stimulating effect of glucocorticoids on SP-A rat gene transcription in vivo. This hormonal effect may be mediated by a putative glucocorticoid responsive element located 140 bp upstream from the initiation site and protected against DNase 1 digestion in footprinting experiments. In vitro transcription of a G-free reporter cassette linked to the 212-bp 5' flanking DNA fragment has established that this putative promoter region is functional. Efficient transcription of the G-free reporter cassette was obtained with cell-free fetal lung extracts, whereas no transcript was detectable with cell-free liver extracts. Comparative analysis of the human and rat 5' flanking sequences shows the presence of strongly conserved motifs, unrelated to previously known consensus sequences. Some of these motifs, specifically protected in DNase 1 footprinting studies, could therefore be involved in the regulation of SP-A gene expression.