[Variables determining the amount of care for very preterm neonates: the concept of medical stance]. / Diversité inter-régionale de la quantité de soins délivrés aux grands prématurés : notion de « regard médical ¼

OBJECTIVE: To compare the amount of medical interventions on very preterm neonates (24-31 weeks of gestation) in two French university tertiary care centers, one of which is involved in a Neonatal Developmental Care program. A secondary objective is to assess whether this difference in medical interventions can be linked to a difference in mortality and morbidity rates. METHODS: We prospectively included all very preterm neonates free from lethal malformation born live in these two centers between 2006 and 2010. These inclusion criteria were met by 1286 patients, for whom we compared the rate of five selected medical interventions: birth by caesarean section, chest intubation in the delivery room, surfactant therapy, pharmacological treatment of patent ductus arteriosus, and red blood cell transfusion. RESULTS: The rates of the five medical interventions were systematically lower in the center that is involved in Neonatal Developmental Care. There was no significant difference in survival at discharge with no severe cerebral ultrasound scan abnormalities between the two centers. There were, however, significantly higher rates of bronchopulmonary dysplasia and nosocomial sepsis and longer hospital stays when the patients were not involved in a Neonatal Developmental Care program. DISCUSSION: This benchmarking study shows that in France, in the first decade of the 21st century, there are as many ways to handle very preterm neonates as there are centers in which they are born. This brings to light the concept of medical stance, which is the general care approach prior to the treatment itself. This medical stance creates the overall framework for the staff's decision-making regarding neonate care. The different parameters structuring medical stance are discussed. Moreover, this study raises the problematic issue of the aftermath of benchmarking studies when the conclusion is an increase of morbidity in cases where procedure leads to more interventions.

[Advantage of delayed umbilical cord clamping in the newborn infant]. / Intérêt du clampage retardé du cordon ombilical chez le nouveau-né

The timing of umbilical cord clamping remains controversial. Although most maternity wards use the early clamping (5-15s), randomized studies and meta-analyses have demonstrated the benefit of delayed clamping for term and preterm newborn infants over the past 10 years. Indeed, placentofetal transfusion of 20-30 ml/kg in 2-3 min improves the iron status of term infants and prevents infant hypochromic anemia. Infant anemia is a public health problem in many developing countries. For preterm newborns, placental transfusion for 45 s or milking the cord for 15 s improves cardiovascular adaptation, with better hemodynamic stability, as well as decreased intraventricular hemorrhages, need for transfusion, and late-onset sepsis. A new look at this symbolic act is needed and professionals need to be persuaded of the importance of the "wait a minute" policy for a better physiological delivery.

[Very preterm birth: is maternal anesthesia a risk factor for neonatal intubation in the delivery room?]. / Le risque d'intubation des grands prématurés en salle de naissance est-il lié au type d'anesthésie maternelle ? Expérience des réseaux périnatals Poitou-Charentes et Franche-Comté

OBJECTIVE: To assess the risk of tracheal intubation at birth in very premature neonates related to the type of maternal anesthesia in case of elective cesarean. POPULATION AND METHODS: All 219 live-born very premature neonates (28-32 weeks of gestation), delivered after an elective cesarean in the 27 maternity wards of 2 French semi-rural neonatal networks. Eighty-three percent (182/219) were delivered in level III maternity wards in university hospitals. RESULTS: Of the very preterm neonates, 33.3% (73/219) were intubated in the delivery room, either for respiratory distress syndrome or a low APGAR score. Very preterm neonates delivered after maternal general anesthesia were more often intubated than those delivered after spinal anesthesia (48.7% vs 25.2%; OR: 2.8; 95% CI: 1.8-5.1). The risk of intubation related to maternal general anesthesia remained statistically significant after an adjustment for gestational age, fetal growth retardation, respiratory distress syndrome, type of maternity ward, and a propensity score that took into account maternal sociodemographic characteristics and the causes of very preterm birth (aOR: 3.4; 95% CI: 1.4-8.2). The risk of intubation related to general anesthesia was lower after adjusting for the 5-min APGAR score (aOR: 2.8; 95% CI: 1.0-7.3). CONCLUSION: Very preterm neonates delivered after cesarean with general anesthesia require tracheal intubation in the delivery room more often than those delivered with spinal anesthesia. This study cannot assess a causal link between anesthesia and the need for neonatal intubation. However, neonatologists have to be aware of the type of maternal anesthesia because it may interfere with the non-invasive ventilation support policy of the very preterm neonate.

[Air embolism on central venous access in a premature neonate, beware of the infusion device assembly! ]. / Embolie gazeuse sur cathéter central chez un nouveau-né prématuré, méfiez-vous de votre montage de perfusion !

A fatal pulmonary air embolism, confirmed by an oriented necropsy, is described in a 25-day-old premature and small-for-gestational-age neonate. The embolism was suspected after air bubbles were detected in the infusion line. The air bubbles originated from a male Luer-lock to male Luer-lock connector, which was part of a specific assembly of the perfusion line. A solution to this problem is thereby proposed. We recommend caution in using complex infusion line assemblies because such complications are probably underestimated.

Molecular epidemiology of Enterobacter cloacae in a neonatal department: a 2-year surveillance study.

A surveillance program was implemented to investigate the molecular epidemiology of Enterobacter cloacae in neonatal units. This program ran for 2 years and involved screening for E. cloacae intestinal colonization of all infants at admission and weekly thereafter. In addition, mothers whose children were admitted to neonatal units were also screened. Pulsed-field gel electrophoresis analysis was used to establish genetic relationships between strains and to identify mother-to-child transmission. During the survey period, 166 (22.6%) of the 735 included children had E. cloacae intestinal colonization, and 29 (3.9%) patients gave clinical samples positive for E. cloacae. Genotyping revealed 90 different pulsotypes in the 199 clinical and screening isolates from neonates, including three major epidemic clones. Mother-to-child transmission of E. cloacae was directly responsible for 8.8% of intestinal colonization of the neonates. This surveillance program reveals a major contribution of patient-to-patient transmission and the rarity of mother-to-child transmission in the spread of E. cloacae in neonates. This highlights the importance of good compliance with infection control procedures by health-care workers.

[Involvement of thyroid gland at non-Hodgkin lymphoma initial diagnosis: 2 pediatric cases]. / Goitre thyroïdien révélateur d'un lymphome non hodgkinien: à propos de 2 cas.

Extranodal thyroid lymphomatous involvement is rare in childhood. We report here 2 children, 1 with vertical transmission-acquired human immunodeficiency virus (HIV), presenting with lymphomatous infiltration of the thyroid gland at diagnosis. One child had infra-clinical endocrine impairment and both responded well to chemotherapy. Although the cases are too scarce to be affirmative, thyroid gland involvement doesn't seem to alter the good prognosis of childhood Burkitt's lymphoma. The third child's cancer in frequency is Non-Hodgkin Lymphomas. Presenting as the initial AIDS event in 1 patient, this case report also highlights the need to systematically propose antiretroviral therapy in vertically HIV infected children.

Does smoking in pregnancy modify the impact of antenatal steroids on neonatal respiratory distress syndrome? Results of the Epipage study.

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.

[Obstetrical and neonatal prognosis of monoamniotic twin gestations]. / Pronostic obstétrical et néonatal des grossesses gémellaires monoamniotiques.

Monoamniotic twin gestations result from a late division of the fertilized ovum with development of the two embryos within a common amnionic sac. We performed a retrospective study in our university hospital on nearly 19 years of clinical activities; we found 16 cases of monoamniotic twins. Obstetrical and neonatal outcomes were analyzed and compared to the data in the literature. The pronosis after 28 weeks of gestation does not appear to be influenced by this type of twin gestation and we demonstrate in this study that vaginal delivery is possible and not deleterious.

Acute vanishing bile duct syndrome after ibuprofen therapy in a child.

We report the case of a 10 year-old girl who had Stevens-Johnson syndrome and cholestasis after ibuprofen therapy. Liver histology was compatible with vanishing bile duct syndrome. She received ursodeoxycholic acid, and liver tests normalized within 7 months. This report confirms that ibuprofen may induce acute vanishing bile duct syndrome.

[Neonatal resuscitation in the delivery room: educational process and evaluation]. / Réanimation du nouveau-né en salle de naissance : démarche pédagogique et évaluation.

Based upon a three necessities basis: public health, biological and medico-legal, this article presents the state of the art about teaching neonatal resuscitation in the delivery room. The educational process is present worldwide; main experiences are described. Evaluation of these actions varies in the literature. We analyze the evaluation of the process of the trained professionals, their satisfaction, the changes in their practices, their theoretical and practical levels, and the impact on newborns' health. We propose a few measures to make official this kind of teaching in France, with a certificate for instructors and trained professionals.

[An appreciation of maternal smoking with high-performance liquid chromatographic determination of maternal and neonatal urinary cotinine]. / Appréciation du tabagisme maternel et néonatal par un dosage de la cotinine urinaire par chromatographie liquide haute performance.

OBJECTIVE: To study the correlation of urinary cotinine levels in mothers and newborns with the number of cigarettes smoked at the end of pregnancy. Population and methods. We recorded the smoking habits of 123 mothers attending a university maternity clinic and measured urinary cotitine levels in mothers and their newborns. All mothers were Europeans and gave birth to a normal full-term (37 weeks gestation) infant. Cotinine levels were measured with high-performance liquid chromatography from urine samples taken during the 6-hour period prior to or after delivery for the mothers and 24-h after birth for the newborns. RESULTS: The average cotinine level for non-smoking mothers, for those who smoked one to nine cigarettes a day and heavy smokers (ten or more cigarettes per day) were 0.21, 2.17 and 4.28 mol/l respectively (p<0.001). The average levels in their newborns were 0.04, 0.39 and 1.36 mol/l respectively (p<0.001). Thirteen percent of the mothers who claimed they did not smoke had cotinine levels higher than the significance cut-off (0.3 mol/l). There was a significant correlation 1) between the number of cigarettes the mothers stated they smoked at the end of pregnancy and their urinary cotinine concentrations (cotinine level=0.213 + 0.349 cigarettes, r=0.78, p<0.001); 2) between the number of cigarettes smoked and newborn's urinary cotinine concentration (cotinine level=0.002 + 0.104 cigarettes/day, r=0.81, p<0.001); and 3) between the mother's and the newborn's urinary cotinine concentrations (newborn cotinine=0.027 + 0.219 maternal cotinine, r=0.77, p<0.001). CONCLUSION: The number of cigarettes smoked at the end of pregnancy accounts for roughly 50% of the variance in the mother's urinary cotinine level and that in her newborn at birth. The urinary cotinine concentration in newborns is 3 to 5 times lower than that of their mothers. A woman smoking 3 cigarettes per day has a urinary cotinine concentration of 1 mol/l. The urinary cotinine level in newborns is 1 mol/l for mothers smoking 10 cigarettes per day.

[Neurodevelopmental outcome of premature infants born at less than 33 weeks of gestational age and not cerebral palsy at the age of 5 years]. / Devenir neurodéveloppemental à cinq ans des prématurés nés avant 33 semaines d'aménorrhée et indemnes d'infirmité motrice d'origine cérébrale.

AIM: To appreciate the impact of prematurity, fetal hypotrophy and familial environment on the neurodevelopmental performances of very premature infants without cerebral palsy at the age of five years. POPULATION AND METHODS: We followed a regional cohort of 171 very premature infants (< or = 32 weeks of gestation) until they were five years of age. Cognitive functions were tested with the WPPSI test and the development quotient was assessed by the ability to draw a "bonhomme". Twenty-two premature infants suffered from cerebral palsy diagnosed before the age of two years. Another infant had a moderate diplegia at the five-year examination. We had no information for 16 prematures (9.3% of survivors). Twenty-eight premature infants were considered as having no severe disability on phone or mailed contact, and another child had a severe isolated mental retardation. We examined 104/148 infants, and 96/148 survivors without cerebral palsy passed the tests. The cognitive functions of these premature infants are compared to the performances of a control group made up of 108 children born at term > or = 37 weeks, matched for birthplace and single or twin characteristics of the pregnancy. RESULTS: The values of the different quotients are significantly decreased in the preterm group. The global IQ and the performance IQ are 0.8 SD, verbal IQ is 0.5 SD and the development quotient is 0.4 SD below the values observed in the control group. A performance IQ less than -2 SD for the mean of the control group is observed three times more than in the controls (13.5% vs 3.7%, P < 0.01). Multiple linear regression shows that prematurity explains, independent of hypotrophy and socioeconomic environment, 8% of the variation of the performance IQ (P < 0.01), 2% of the variation of the verbal IQ and 2% of the development quotient (P < 0.05). CONCLUSION: The five-year neurologic outcome of the children born prematurely in this regional study is similar to the results observed in regional studies conducted in Europe: 13.4% of the survivors have cerebral palsy, and the cognitive functions of the children with no cerebral palsy are significantly lower than the term control group. Other risk factors such as hypotrophy, which modulates the developmental quotient, and the socioeconomic status, which modulates the verbal IQ, are underlined.

[For what reasons is the neurologic status of very premature infants altered between 1 and 2 years in a follow-up study? The contribution of a Frache-Comté region study]. / Pour quelles raisons le statut neurologique des grands prématurés se modifie-t-il entre un et deux ans dans une enquête de suivi? Apport de l'enquête franc-comtoise.

BACKGROUND: The purpose of this population-based study was firstly to compare the neuro-developmental outcome at one and two years of very preterm infants, and secondly, to identify the risk factors for a misdiagnosis of cerebral impairment at the age of one year. POPULATION AND METHODS: The preterm cohort included 203 infants born between 25 and 32 weeks of gestational age in the region of Franche-Comté (France) during a two-year period. The control group included 196 full-term infants born in the same maternity wards. Neuro-developmental assessments were performed by pediatricians or physicians, both at one and two years of age, on 94% (161/171) surviving preterms and 89% (173/195) full-terms. RESULTS: There is a fair correlation between the two neurological evaluations of the control group (170/173, 98% have the same classification at the age of one and two). There is a weak correlation (kappa = 0.37) between the two neurological evaluations of the preterm group. Sixteen preterms (10%) had been classified more abnormal at one year than they were at two years. The presence of a broncho-pulmonary dysplasia, linked to male sex and extreme prematurity, was statistically linked to this first kind of misclassification. Seventeen preterms (10%) had been considered more normal at one year than they were at two years. The presence of a diplegia, family precariousness and the examination at one year of age by a general practitioner were statistically linked to this second kind of misclassification. CONCLUSION: This prospective population-based study identifies structural situations (bronchopulmonary dysplasia linked to extreme prematurity) and environmental situations (family precariousness, examiner's qualifications) linked to a misclassification of the neurological status of one-year-old former preterm infants.

[Smith-Lemli-Opitz syndrome]. / Le syndrome de Smith-Lemli-Opitz.

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is an autosomic recessive metabolic affection. Children affected by SLOS exhibit a defect in cholesterol biosynthesis associated with a high concentration of cholesterol precursor 7 dehydrocholesterol (7 DHC) and its isomers, which is due to an enzymatic block at the level of delta-7-DHC reductase. SLOS has been subdivided into two types on the basis of clinical severity: type I is the classic and type II is the severe one. CASE REPORT: A full term female was born from a pregnancy complicated by oligoamniosis and intra-uterine growth retardation. The neurologic status was immediately impaired with severe hypotonia, absence of reflexes, and abnormal crying. She exhibited multiple congenital anomalies with a facial dysmorphia, anomalies of members, unicornus uterus and a pyloric stenosis. Plasmatic concentration exhibited a normal cholesterolemia contrasting with an elevated level of 7 and 8 DHC. Major alimentary tract defect led to enteral and parenteral nutrition. The severe neurological defect led to death on the 16th day of life. CONCLUSION: Despite normal blood cholesterol levels that can be attributed to enteral and parenteral nutrition, the severity of clinical findings and the lethal course permit to classify this case as type II.

Some risk factors for cerebral palsy in very premature infants: importance of premature rupture of membranes and monochorionic twin placentation.

OBJECTIVE: To delineate the perinatal risk factors of neurodevelopmental disabilities in very preterm birth applying logistic regression analysis. DESIGN: This prospective, geographically defined collaborative study was carried out in the Franche-Comté region of France. SUBJECTS: From October 1, 1990 to September 30, 1992, perinatal and follow-up data were collected on 203 consecutive live-born singleton or twin non-malformed infants with strictly ascertained gestational ages of less than 33 weeks. MAIN OUTCOME MEASURE: The rate of cerebral palsy and/or severe mental retardation as diagnosed by a family physician or pediatrician with a screening-skill test performed at 2 years of age. RESULTS: 167/171 (98%) survivors were evaluated. Twenty-two of the 167 examined infants (13%) showed signs of cerebral palsy, and 10 of these had severe cerebral palsy or mental retardation. Risk factors for disabilities were selected by a multivariate approach: premature rupture of membranes >/=48 h (OR 4.3, 95% CI 1.6-11.8); monochorionic twin placentation (OR 6.0, 95% CI 1.7-21.3), and respiratory distress syndrome (OR 2.8, 95% CI 1.1-7.1). CONCLUSION: This geographically defined prospective study gives epidemiological data and highly suggests that there is a link between prenatal events (premature rupture of membranes, monochorionic twin placentation), postnatal events (respiratory distress syndrome), and neurological disabilities in former preterm infants.

[Neurologic development in premature infants under 33 weeks of gestational age: determination of risk of neurological abnormalities in a prospective regional survey with a control group]. / Devenir neurologique des prématurés de moins de 33 semaines: détermination du risque d'anomalie neurologique dans une enquête régionale prospective avec groupe témoin.

AIM: The purpose of this population-based study was to compare the incidence of neurodevelopmental disability and its risk factors between preterm and full-term infants matched as control group. POPULATION AND METHODS: The preterm cohort included 203 infants born between 25 and 33 weeks of gestational age in the region of Franche-Comté (France) during a two-year-period. The control group included 196 full-term infants born in the same maternities. Survival up to the date of follow-up was 171/203 (84%) for preterms and 195/196 (99.5%) for full-term infants (uncorrected age, mean 12 months). Neurodevelopmental assessments were performed by pediatricians or physicians on 164/171 surviving preterms (96% follow-up) and 179/195 full-terms (92%). RESULTS: Thirty-two (19.5%) preterm infants had disability, ten of these (6%) showing severe disability. Five (2.8%) full-term infants had disability, one of these (.5%) having severe disability. Risk factors predicting a disability included in a multivariate approach: prematurity (odds-ratio [OR]: 7.8), maternal age > 37 (OR: 3.0), lack of profession for both parents (OR: 3.7), male gender (OR: 2.9). The pediatrician observed a disability more frequently than the physician (OR: 2.46). Likewise, risk factors predicting a severe disability included: prematurity (OR: 10.8), lack of profession for both parents (OR: 5.8) and monochorial twin-placentation (OR: 4.5). CONCLUSIONS: Prematurity is not the only risk factor to be taken into account for neurodevelopmental evaluation of premature infants, but its influence still remains widely predominant.

Apparent segregation of null alleles ascribed to deletions of the ornithine transcarbamylase gene in congenital hyperammonaemia.

Ornithine transcarbamylase (OTC) deficiency is an X-linked disorder of the urea cycle mapped to chromosome Xp21.1. Here, we show that apparent segregation of null alleles at the OTC locus and flanking polymorphic loci mimicked false maternity or false paternity in three affected families. Based on these observations, we suggest giving consideration to gene deletion when dealing with segregation of null alleles in OTC deficiency.