Review shows that using surfactant a number of times or as a vehicle for budesonide may reduce the risk of bronchopulmonary dysplasia.

AIM: Bronchopulmonary dysplasia (BPD) remains the most common respiratory morbidity in immature infants. This review describes the diagnosis of BPD has evolved and summarises the therapeutic approaches that have made it possible to limit the incidence of BPD. METHOD: We reviewed the literature from the first definition of BPD by Northway in 1967 to the surfactant treatment policies that are currently in use, drawing on more than 50 papers up to 2017. RESULTS: Our review showed that improvements in neonatal survival have been associated with an increased risk of severe BPD, significant levels of long-term morbidity and the increased use of healthcare resources. These issues have encouraged researchers to explore potential new treatments that limit the incidence of BPD. Repeated surfactant instillation and the use of surfactant as a vehicle for budesonide are promising strategies for alleviating the burden of chronic lung disease. Ongoing research on surfactant or stem cell therapy may further improve the respiratory prognosis for prematurely born children. CONCLUSION: Considerable research has been carried out into the increase in BPD, which has resulted from improvements in neonatal survival. Key areas of research include repeated surfactant administration, using surfactant as a vehicle for budesonide and stem cell therapy.

Three new cases of the Schinzel-Giedion syndrome and review of the literature.

Three fetuses with normal chromosomes were found to have uni- or bilateral hydronephrosis during the third trimester of pregnancy. At birth, they presented with coarse face, hypertelorism, and a deep groove under the eyes. Fontanelles and sutures were wide open. Genital abnormalities were present in 2 cases. Skeletal radiographs showed delayed bone maturation, broad and dense ribs, and a wide synchondrosis between the exoccipital and supraoccipital bones. The combination of such findings suggested the diagnosis of Schinzel-Giedion syndrome. Two patients died soon after birth, whereas the third one developed severe mental and motor retardation with seizures and spasticity, and died at 18 months. Schinzel-Giedion syndrome is rare and likely to be inherited as an autosomal recessive trait. So far, 13 well-documented cases have been reported allowing major and minor traits of the syndrome to be distinguished. Since no genetic marker is available, the prenatal diagnosis of Schinzel-Giedion syndrome relies on ultrasound examination, especially detection of renal abnormalities.

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.

Development and initial validation of the EDIN scale, a new tool for assessing prolonged pain in preterm infants.

OBJECTIVE: To develop and validate a scale suitable for use in clinical practice as a tool for assessing prolonged pain in premature infants. METHODS: Pain indicators identified by observation of preterm infants and selected by a panel of experts were used to develop the EDIN scale (Echelle Douleur Inconfort Nouveau-Né, neonatal pain and discomfort scale). A cohort of preterm infants was studied prospectively to determine construct validity, inter-rater reliability, and internal consistency of the scale. RESULTS: The EDIN scale uses five behavioural indicators of prolonged pain: facial activity, body movements, quality of sleep, quality of contact with nurses, and consolability. The validation study included 76 preterm infants with a mean gestational age of 31.5 weeks. Inter-rater reliability was acceptable, with a kappa coefficient range of 0.59-0.74. Internal consistency was high: Cronbach's alpha coefficients calculated after deleting each item ranged from 0.86 to 0.94. To establish construct validity, EDIN scores in two extreme situations (pain and no pain) were compared, and a significant difference was observed. CONCLUSIONS: The validation data suggest that the EDIN is appropriate for assessing prolonged pain in preterm infants. Further studies are warranted to obtain further evidence of construct validity by comparing scores in less extreme situations.

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.

Perinatal factors affecting survival and survival without disability of extreme premature infants at two years of age.

OBJECTIVE: To study obstetrical factors leading to very preterm delivery (between 24 and 28 weeks) and to relate these factors to neonatal outcome and psychomotor development at two years. STUDY DESIGN: Among 144 infants born alive before 28 weeks of gestation at a single perinatal center between January 1993 and December 1996, we analyzed the influence on neonatal outcome and on psychomotor development at 24 months of a variety of perinatal and neonatal factors. Psychomotor development at two years was classified as: normal, borderline, or moderately or severely handicapped. RESULTS: During the study period, 114 women delivered live infants before 28 weeks' gestation: 87 singletons, 25 sets of twins, 1 set of triplets and 1 set of quadruplets. All 144 live-born infants received neonatal resuscitation: 50 died before discharge. At two years of age, 6 of the 94 survivors were lost to follow-up. Assessments of the psychomotor development of the other 88 was normal for 52%; borderline for 20%, moderately handicapped for 20%, and severely handicapped for 8%. Multivariate analysis found that two factors affected survival: birthweight and fetal heart rate. (The 42% of infants with a birthweight below 700 g survived versus 83% above 900 g, P<0.001, OR=5.2, 95% CI (confidence interval) [2.4-11.2].) CONCLUSION: These data show the influence of perinatal factors on the outcome of very preterm infants; birthweight and fetal heart rate are strongly correlated with survival. Gestational age is a good predictor of psychomotor development at two years.

Periventricular leukomalacia and mode of delivery in twins under 1500 g.

BACKGROUND: The optimal mode of delivery in twin gestations remains undefined, particularly for twins weighing less than 1500 g. OBJECTIVE: To evaluate the impact of the mode of delivery on neonatal outcome in twins below 1500 g. MATERIALS AND METHODS: In this multicenter cohort study during 1999, 66 sets of twins born in hospital and weighing below 1500 g formed our study group. Antenatal and neonatal parameters and their relationship to mode of delivery were studied, based on a factor analysis. Analysis of covariance was used to assess the effect of the mode of delivery on postnatal factors, with antenatal parameters used as covariates. RESULTS: Statistical analysis showed that infants delivered vaginally had significantly more periventricular leukomalacia than those children delivered by Cesarean section (p = 0.03). The estimated odds for leukomalacia were higher in the vaginal than in the Cesarean group when adjusted for covariates (OR = 4.7; 95% CI = 1.0, 25.15). CONCLUSION: Routine Cesarean section should be recommended in twin gestations with infants weighing less than 1500 g, regardless of gestational age or fetal presentation.

[Platelet transfusions in neonatology]. / Transfusions plaquettaires en néonatalogie.

Thrombocytopenia occurs in 20% to 40% of infants admitted to a neonatal intensive care unit. Approximately 30% of the newborns with severe thrombocytopenia below 50.10(9)/l platelets receive platelet transfusions. The etiology may be: bacterial infection, DIC and immune mediated thrombocytopenia. The consequences of thrombocytopenia are significant risks of severe intracranial hemorrhage and neurologic morbidity. Therapeutic platelet transfusions are given to actively bleeding neonates with less than 50.10(9)/l platelets. Prophylactic platelet concentrates are usually given to infants with platelets counts below 20.10(9)/l. The standard platelet concentrate (CMV-negative donor) is the product of choice for newborns. Fetal intracranial hemorrhage is possible as soon as 20 weeks of gestation in allo-immune thrombocytopenia. Actually percutaneous umbilical blood sampling is very useful to measure fetal platelets count in order to decide in utero maternal platelet transfusion. Maternal irradiated plateletpheresis concentrates are preferentially infused in this indication. At the end of pregnancy, cesarean section is preferred to normal vaginal delivery if fetal thrombocytopenia below 100.10(9)/l is observed. In pregnant women with auto-immune thrombocytopenia, the decision to carry out percutaneous umbilical blood samples should be weigh relatively to the 3-5% estimated risk of serious consequences. Platelets transfusions are particularly successful in immune thrombocytopenia but less effective in other clinical circumstances.

[Periventricular leukomalacia. I. Histological and pathophysiological aspects]. / Les leucomalacies périventriculaires. I. Aspects histologiques et étiopathogéniques.

The term 'periventricular leukomalacia' (PVL) usually covers necrotic and/or gliotic lesions from perinatal origin occurring in the periventricular ring of telencephalic white matter. PVLs are found post-mortem in one third of brains from autopsies of premature infants; PVLs are diagnosed in 4 to 10% of infants born before 33 weeks of gestation and remaining alive more than 3 days after birth. PVL is very rare in at term infants. The proportion of PVLs from prenatal origin is estimated between one third and one half of cases. Recent progresses in neuroepidemiology, developmental neurobiology and imaging methods permit to revisit the pathophysiology of PVLs on a multifactorial basis. The final result of these multiple factors seem to be calcium influx due to glutamatergic overactivation triggered by cytokines, infection and inflammation, and deficit in neurotrophic factors. Periventricular topography can be explained by properties of intracerebral vascular wall at this stage of angiogenesis and by perfusion failure/hypoxia.

[Periventricular leukomalacia and brain protection. II. Diagnosis, sequelae and neuroprotection]. / Les leucomalacies périventriculaires. II. Diagnostic, séquelles et neuroprotection.

The term 'periventricular leukomalacia' (PVL) usually covers necrotic and/or gliotic lesions from perinatal origin occurring in the periventricular ring of telencephalic white matter. Carrying motor and neuropsychological consequences, PVLs could be the most severe danger for very premature brains. Positive rolandic sharp waves recorded on EEG and precocious abnormally echogenous periventricular images on ultrasound suggest prospective periventricular cysts. Cystic periventricular cavitations certify the diagnosis of PVL. More subtle lesions of PVL do not reach the cystic grade and their diagnosis is confirmed by MRI. Treatment of infections is already available and potentially a tool for prevention. When the overwhelming glutamatergic signal has been triggered, neuroprotective agents turning off the excitotoxic cascade, including calcium blockers, growth factors and others, are promising therapeutic tools.

[Pain symptomatology in premature infants]. / Sémiologie de la douleur chez le prématuré.

BACKGROUND: Assessing pain in premature babies is difficult because of their limited capacities to communicate. The aim of this study was to recognize manifestations of acute and chronic pain or, on the contrary, of well-being state, and to validate a "pain scale" for premature babies. POPULATION AND METHODS: Premature babies less than 28 days of age (most of them less than 32 weeks of gestational age) were carefully observed during their stay in a neonatal intensive care unit by nurses, physicians, physiotherapists and a psychiatrist. All signs and symptoms were collected during situations a priori painful and compared to the behavior of the well-being states. Photographs and videofilms were also analysed. RESULTS: Five items, scored from 0 to 4, were established, based on facial activity, movements and posture of the body, quality of sleep, relationship with the examiner, and efficacy of measures of comforting. These items permitted to describe four patterns corresponding to 1: well-being status, 2: acute pain, 3 and 4: durable pain or discomfort either through clinical picture of irritability or motionlessness. A strict concordance of scores for the five items between the different examiners was found in 80% of the 50 babies studied. The sensibility of the scale (studied in 12 babies) appeared accurate (77% of variation of the scores during hospitalization). CONCLUSIONS: An objective assessment of pain and discomfort in premature babies can be made using a "pain scale" useful for care and therapeutic decisions.

[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.

[Pediatric follow-up network in the south Ile-de-France]. / Le réseau de suivi pédiatrique du sud de l'Ile-de-France.

Regional organization of perinatal care, with maternal tranfers, has largely contributed to the increasing survival rate of very preterm infants. Nevertheless, follow-up and care the of these surviving children at risk of neurodevelopmental impairment are insufficiently organized. For this reason, a pediatric network of care and follow-up has been set up in continuity of a regional perinatal network ("réseau périnatal et réseau pédiatrique du sud-ouest de l'Ile de France"). Two missions are devoted to this network: organize local follow-up and care of infants at risk of abnormal outcome and collect follow-up data with specific forms. One form per year of age is to be filled with Items concerning growth, health, cognitive and motor development, family and society integration, quality of life.

[Anoxic encephalopathy of the term neonate and brain hypothermia]. / Encéphalopathie anoxique du nouveau-né à terme et hypothermie cérébrale.

The outcome of term newborns with birth asphyxia and moderate to severe hypoxic ischemic encephalopathy remains very poor. After the primary phase of energy failure during asphyxia, neuronal cell metabolism may deteriorate in a secondary phase of brain injury. The window between these two phases opens the way to potential neuroprotective treatments such as brain cooling. Promising experimental data on controlled hypothermia need to be examined with clinical trials.

[What does remain about bronchopulmonary dysplasia?]. / Que reste-t-il de la dysplasie bronchopulmonaire?

Bronchopulmonary dysplasia is defined as prolonged respiratory failure resulting from sequellae after neonatal intensive care in premature infants. Functional impairment continues into adult life. There are two main causal factors: the initial respiratory disease and pulmonary immaturity. Up through the nineties, bronchopulmonary dysplasia was a major problem in neonatal intensive care units; mortality reached 20% of infants requiring artificial ventilation for 1 or 2 months. Despite the rising rate of premature births (currently 2%) considerable progress has been made in the treatment of bronchopulmonary dysplasia. The question is whether the infants in the current generation with still suffer into adult life. Advances in preventive therapy have included antenatal corticosteroid therapy, use of exogenous surfactants and progressive improvement in ventilatory assistance techniques. Improved neonatal care to relieve pain and maintain nutrition have also had an important effect. Specific treatments include the use of salbutamol spray to reduce bronchospasme and improve respiratory compliance. The initial hopes placed in inhaled corticosteroids were unfortunately recently shown to be unfounded. Due to the large number of premature infants it appears difficult to predict the future situation of bronchopulmonary dysplasia, but current data show a clear tendancy towards regression of the disease. Three preventive measures could further reduce the incidence: better coordination between obstetricians and pediatricians, extension of antenatal corticosteroid therapy and the development and improvement of continuous positive pressure ventilation.

[Bronchopulmonary dysplasia]. / Dysplasie bronchopulmonaire.

Bronchopulmonary dysplasia (BPD) is one of the most serious complications of neonatal intensive care. This chronic lung disease usually follows early pulmonary injuries. Surfactant defect, oxygen toxicity and barotrauma are three major factors leading to diffuse alveolar and bronchiolar damage, first step of BPD. BPD usually appears in preterm infants and correlates with degree of prematurity and the severity of neonatal distress syndrome. Infants with BPD frequently have poor outcome; the mortality rate is near 30%. The long-term survival prognosis is uncertain with a risk of bronchopathy in adulthood. Until date, current management of BDP is unsuccessful. New strategies are required to prevent neonatal respiratory distress syndrome and decrease its severity.