Maintenance of methylation profile in imprinting control regions in human induced pluripotent stem cells.

BACKGROUND: Parental imprinting is an epigenetic mechanism that leads to monoallelic expression of a subset of genes depending on their parental origin. Imprinting disorders (IDs), caused by disturbances of imprinted genes, are a set of rare congenital diseases that mainly affect growth, metabolism and development. To date, there is no accurate model to study the physiopathology of IDs or test therapeutic strategies. Human induced pluripotent stem cells (iPSCs) are a promising cellular approach to model human diseases and complex genetic disorders. However, aberrant hypermethylation of imprinting control regions (ICRs) may appear during the reprogramming process and subsequent culture of iPSCs. Therefore, we tested various conditions of reprogramming and culture of iPSCs and performed an extensive analysis of methylation marks at the ICRs to develop a cellular model that can be used to study IDs. RESULTS: We assessed the methylation levels at seven imprinted loci in iPSCs before differentiation, at various passages of cell culture, and during chondrogenic differentiation. Abnormal methylation levels were found, with hypermethylation at 11p15 H19/IGF2:IG-DMR and 14q32 MEG3/DLK1:IG-DMR, independently of the reprogramming method and cells of origin. Hypermethylation at these two loci led to the loss of parental imprinting (LOI), with biallelic expression of the imprinted genes IGF2 and DLK1, respectively. The epiPS™ culture medium combined with culturing of the cells under hypoxic conditions prevented hypermethylation at H19/IGF2:IG-DMR (ICR1) and MEG3/DLK1:IG-DMR, as well as at other imprinted loci, while preserving the proliferation and pluripotency qualities of these iPSCs. CONCLUSIONS: An extensive and quantitative analysis of methylation levels of ICRs in iPSCs showed hypermethylation of certain ICRs in human iPSCs, especially paternally methylated ICRs, and subsequent LOI of certain imprinted genes. The epiPS™ culture medium and culturing of the cells under hypoxic conditions prevented hypermethylation of ICRs in iPSCs. We demonstrated that the reprogramming and culture in epiPS™ medium allow the generation of control iPSCs lines with a balanced methylation and ID patient iPSCs lines with unbalanced methylation. Human iPSCs are therefore a promising cellular model to study the physiopathology of IDs and test therapies in tissues of interest.

How can we improve perinatal care in isolated multiple intestinal atresia? A retrospective study with a 30-year literature review.

INTRODUCTION: Multiple intestinal atresia (MIA) is a rare cause of neonatal intestinal obstruction. To provide an overview of the current prenatal, surgical, and nutritional management of MIA, we report our experience and a literature review of papers published after 1990. METHODS: All cases of isolated MIA (non-hereditary, not associated with apple-peel syndrome or gastroschisis) treated at our institution between 2005 and 2016 were reviewed and compared with cases found in the literature. RESULTS: Seven patients were prenatally suspected of having intestinal obstruction and were postnatally diagnosed with MIA, with a mean 1.7 (1-2) resections-anastomoses (RA) and 6 (1-10) strictureplasties performed, resulting in a mean resected bowel length of 15.1cm (15-25 cm). Median time to full oral feed was 46 days (14-626 days). All patients were alive and none had orality disorder after a mean follow-up of 3.1 years (0.2-8.1 years). Three surgical strategies were found in the literature review: multiple RA (68%, 34/50) including Santulli's technique in four of 34 (12%) and anastomoses over a transanastomotic tube (32%, 16/50), with a 98% survival rate, and short-bowel syndrome for only two patients. CONCLUSION: Bowel-sparing surgery and appropriate medical management are key to ensuring a favorable nutritional and gastrointestinal outcome and a good prognosis. Prenatal assessment and standardization of the surgical course of treatment remain challenging.

A randomised controlled trial of amnioexchange for fetal gastroschisis.

OBJECTIVE: Morbidity in fetuses affected by gastroschisis is mainly the result of bowel ischaemic and inflammatory processes. Experimental studies on animal models show that clearing amniotic fluid from the digestive secretions by amnioexchange procedures reduces the inflammatory process. We evaluated the benefit of the amnioexchange procedure for fetal gastroschisis in humans. DESIGN: Prospective, interventional, randomised study. SETTING: Eight referral centres for fetal medicine. POPULATION: Pregnant women carrying a fetus with gastroschisis. METHODS: We compared, in utero, amnioexchange with a sham procedure. The protocol included, in both arms, steroid injections at 30 weeks of gestation and the use of postnatal minimal enteral feeding. MAIN OUTCOME MEASURES: The primary outcome was a composite variable based on the duration of ventilation and parenteral nutrition. Secondary outcomes were the effectiveness and safety of the amnioexchange procedure, including the rate of perinatal death, time to full enteral feeding, primary closure, and late feeding disorders. RESULTS: Sixty-four patients were randomised. There was no difference in the composite criteria between the amnioexchange and control groups. Based on an intention-to-treat analysis, there were no significant between-group differences in pregnancy outcome or complications. When studying the relationship between digestive compounds and amniotic fluid inflammatory markers, a clear correlation was found between bile acid and both ferritin and interleukin 1ß (IL1ß). CONCLUSIONS: In humans, amnioexchange, as described in our protocol, is not an option for fetal care; however, we provide supplementary proof of the involvement of inflammation in the pathogenicity of gastroschisis and suggest that future research should aim at reducing inflammation. ClinicalTrials.gov: NCT00127946. TWEETABLE ABSTRACT: A prospective, interventional, randomised study shows no benefit of amnioexchange for fetal gastroschisis in humans.

Antenatal antipsychotic exposure induces multigenerational and gender-specific programming of adiposity and glucose tolerance in adult mouse offspring.

Second-generation antipsychotics (SGAs) are well known for their metabolic side effects in humans, including obesity and diabetes. These compounds are maintained during pregnancy to prevent the relapse of psychoses, but they readily diffuse across the placenta to the fetus, as documented with the widely-prescribed drug olanzapine (OLZ). However, observational studies have provided conflicting results on the potential impact of SGAs on fetal growth and body weight, and their effects on metabolic regulation in the offspring. For this reason, our study has tested whether antenatal exposure of CD1 mice to OLZ influenced metabolic outcomes in the offspring of the first (F1) and second (F2) generations. In F1 mice, OLZ antenatal treatment caused a decrease in neonatal body weight in both genders, an effect that persisted throughout life only in male animals. Interestingly, F1 female mice also displayed altered glucose homoeostasis. F2 mice, generated by mating normal males with F1 female mice exposed to OLZ during antenatal life, exhibited higher neonatal body weights which persisted only in F2 female animals. This was associated with expansion of fat mass and a concordant pattern of adipose tissue gene expression. Moreover, male and female F2 mice were glucose-intolerant. Thus, our study has demonstrated that antenatal OLZ exposure induces multigenerational and gender-specific programming of glucose tolerance in the offspring mice as adults, and points to the need for careful monitoring of children exposed to SGAs during pregnancy.

[G6PD deficiency in females with neonatal revelation. Report of four cases]. / Déficit en G6PD chez la fille à révélation néonatale. Revue de 4 cas cliniques.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human erythrocyte enzyme defect, estimated to affect approximately 4 million people worldwide. It is associated with severe neonatal hyperbilirubinemia, which may lead to bilirubin encephalopathy and kernicterus, and with hemolytic crisis. G6PD deficiency is an X-linked enzymopathy affecting hemizygous males, homozygous females, and also a subset of heterozygous females via chromosome X inactivation. We report four cases of female newborns with neonatal hyperbilirubinemia related to a G6PD deficiency and followed by the Centre national de référence en hémobiologie périnatale (CNRHP) from November 2013 to July 2014. Clinical and biological characteristics suggested G6PD deficiency (jaundice observed within the first 24h, severe hyperbilirubinemia, associated with regenerative hemolytic anemia, low response to phototherapy, ethnic origin of the parents from high-incident geographical regions). The family investigations revealed a deficit in G6PD in one of the parents who was unaware of this deficit until then. This article aims to make neonatologists and pediatricians aware of the need to search for an etiology for any severe hyperbilirubinemia and to raise G6PD deficiency in male and female newborns in case of hyperbilirubinemia with hemolysis.

[Congenital cytomegalovirus infection manifesting as neonatal respiratory distress in an HIV-exposed uninfected newborn]. / Pneumopathie congénitale à cytomégalovirus chez un nouveau-né à terme né de mère séropositive pour le VIH.

BACKGROUND: Cytomegalovirus (CMV) is one of the most common intrauterine infections, affecting approximately 1% of all live births. There are few reports on congenital CMV infections manifesting as isolated pneumonitis. CASE REPORT: We report a case of congenital CMV with neonatal respiratory distress affecting an HIV-exposed uninfected infant. This infant required noninvasive ventilation beginning within the first 15min of life. The initial chest X-ray showed diffuse bilateral ground-glass opacifications. Bacterial infection, meconium aspiration and hyaline membrane disease were excluded. Salivary quantitative CMV PCR was positive (2,342,261IU/mL) and serum viral load for CMV was low (476IU/mL). Bronchoalveolar lavage (BAL) performed on day 12 for quantitative CMV PCR was significantly positive (1,045,942IU/mL). Intravenous ganciclovir treatment was started on day 14 (7.5mg/kg/12h) for 2 weeks and oral valganciclovir (15mg/kg/12h) was given for 4 weeks afterwards. Ventilatory support was stopped on day 18. HIV serum viral load was negative on day 30. DISCUSSION: Congenital CMV infection can present as isolated pneumonitis with persistent neonatal respiratory symptoms, emphysematous lung disease, or persistent pulmonary hypertension. If this diagnosis is suspected, and even if CMV viremia remains low, BAL with quantitative CMV PCR must be performed to ascertain the diagnosis and indicate antiviral treatment. HIV-exposed uninfected infants have higher rates of congenital CMV infection when the mother's CD4 rate is<200/mm3. Most cases of CMV transmission in HIV-exposed uninfected infants have occurred by maternal endogenous reactivation or reinfection.

Endothelial dysfunction in individuals born after fetal growth restriction: cardiovascular and renal consequences and preventive approaches.

Individuals born after intrauterine growth restriction (IUGR) have an increased risk of perinatal morbidity/mortality, and those who survive face long-term consequences such as cardiovascular-related diseases, including systemic hypertension, atherosclerosis, coronary heart disease and chronic kidney disease. In addition to the demonstrated long-term effects of decreased nephron endowment and hyperactivity of the hypothalamic-pituitary-adrenal axis, individuals born after IUGR also exhibit early alterations in vascular structure and function, which have been identified as key factors of the development of cardiovascular-related diseases. The endothelium plays a major role in maintaining vascular function and homeostasis. Therefore, it is not surprising that impaired endothelial function can lead to the long-term development of vascular-related diseases. Endothelial dysfunction, particularly impaired endothelium-dependent vasodilation and vascular remodeling, involves decreased nitric oxide (NO) bioavailability, impaired endothelial NO synthase functionality, increased oxidative stress, endothelial progenitor cells dysfunction and accelerated vascular senescence. Preventive approaches such as breastfeeding, supplementation with folate, vitamins, antioxidants, L-citrulline, L-arginine and treatment with NO modulators represent promising strategies for improving endothelial function, mitigating long-term outcomes and possibly preventing IUGR of vascular origin. Moreover, the identification of early biomarkers of endothelial dysfunction, especially epigenetic biomarkers, could allow early screening and follow-up of individuals at risk of developing cardiovascular and renal diseases, thus contributing to the development of preventive and therapeutic strategies to avert the long-term effects of endothelial dysfunction in infants born after IUGR.

[Oxidative stress after preterm birth: origins, biomarkers, and possible therapeutic approaches]. / Stress oxydant chez l'enfant prématuré : causes, biomarqueurs et possibilités thérapeutiques.

The survival of preterm babies has increased over the last few decades. However, disorders associated with preterm birth, known as oxygen radical diseases of neonatology, such as retinopathy, bronchopulmonary dysplasia, periventricular leukomalacia, and necrotizing enterocolitis are severe complications related to oxidative stress, which can be defined by an imbalance between oxidative reactive species production and antioxidant defenses. Oxidative stress causes lipid, protein, and DNA damage. Preterm infants have decreased antioxidant defenses in response to oxidative challenges, because the physiologic increase of antioxidant capacity occurs at the end of gestation in preparation for the transition to extrauterine life. Therefore, preterm infants are more sensitive to neonatal oxidative stress, notably when supplemental oxygen is being delivered. Furthermore, despite recent advances in the management of neonatal respiratory distress syndrome, controversies persist concerning the oxygenation saturation targets that should be used in caring for preterm babies. Identification of adequate biomarkers of oxidative stress in preterm infants such as 8-iso-prostaglandin F2α, and adduction of malondialdehyde to hemoglobin is important to promote specific therapeutic approaches. At present, no therapeutic strategy has been validated as prevention or treatment against oxidative stress. Breastfeeding should be considered as the main measure to improve the antioxidant status of preterm infants. In the last few years, melatonin has emerged as a protective molecule against oxidative stress, with antioxidant and free-radical scavenger roles, in experimental and preliminary human studies, giving hope that it can be used in preterm infants in the near future.

The offspring of the diabetic mother--short- and long-term implications.

In the 1980s, David Barker and Colleagues proposed that the major causes of cardiovascular and metabolic diseases have their roots in early development. There is now robust evidence that an hyperglycemic intrauterine environment is responsible not only for significant short-term morbidity in the fetus and the neonate but also for an increased risk of developing diabetes as well as other chronic, noncommunicable diseases at adulthood. The risk is higher in pregestational diabetes, but unrecognized and/or poorly managed gestational diabetes (GDM) may have similar consequences. Although a relatively clear picture of the pathogenesis of the fetal and neonatal complications of maternal diabetes and of their interrelationship is available today, the intimate molecular mechanisms involved in the long term are far from being understood. While the rate of GDM is sharply increasing in association with the pandemic of obesity and of type 2 diabetes over the world, we review here the current understanding of short- and long-term outcomes of fetuses exposed to a diabetic environment.

[Risk factors for developing pneumothorax in full-term neonates with respiratory distress]. / Détresse respiratoire du nouveau-né à terme : quels facteurs de risque de développer un pneumothorax ?

OBJECTIVES: To describe respiratory distress (RD) in full-term neonates hospitalized in the NICU and to determine risk factors in this population for pneumothorax. STUDY DESIGN: Retrospective inclusion for 4 years of full-term neonates hospitalized for RD before the 2nd day of life. Neonates were separated into Group I (RD with no pneumothorax) and Group II (RD with pneumothorax). Data collected from maternal and newborn medical records were obstetrical, perinatal, and postnatal. P<0.05 was set as the significance level. RESULTS: Ninety-six neonates were included. In this population, 64 (66.7%) were male, 45 (46.9%) were born by cesarean section, and 30 (31.3%) by elective cesarean section. Neonatal outcome was 4.6 days of hospital stay, 47.4% odds of mechanical ventilation, and 17.7% of persistent pulmonary hypertension of the neonate (PPHN). A central catheter was needed in 25% of the patients and amine treatment in 3.1%. The number of neonates born by cesarean section was lower as term increased. Those born by cesarean section were more likely to develop PPHN (26.7 vs 9.8%; P=0.03), and those born without labor were more likely to require oxygen (83.3 vs 63.6%; P=0.05). When comparing Group I and Group II (32 neonates), absence of labor (RR 1.5) and birth outside of a level III maternity unit (RR 1.6) were risk factors for pneumothorax. These results were confirmed in multivariate analysis. In Group II, birth before 39 weeks was a risk factor for bilateral pneumothorax (P=0.01). The median length of hospitalization was significantly longer in Group II than in Group I (5.8 days vs 4 days, P=0.03). CONCLUSIONS: RD at term exposes the infant to high morbidity and pneumothorax, especially if born outside of a level III maternity unit and absence of labor.

[Prenatal intestinal volvulus: A life-threatening event with good long-term outcome]. / Volvulus prénatal du grêle : risque vital immédiat mais bon pronostic à long terme.

BACKGROUND AND AIMS: To describe the outcome of neonates with prenatal intestinal volvulus. PATIENTS AND METHODS: All neonates with prenatal intestinal volvulus managed in our institution between May 2004 and December 2010 were retrospectively studied. All neonates with prenatal or neonatal diagnosis of prenatal intestinal volvulus were included. We analyzed age at diagnosis, fetal ultrasound (US) scan and magnetic resonance imaging (MRI) findings, clinical signs at birth, surgical findings, management, and postoperative outcome. RESULTS: Ten neonates with prenatal intestinal volvulus were identified. Prenatal US scans or MRI demonstrated evidence of meconium peritonitis in one fetus and bowel dilatation in 2 others. The mean gestational age at birth was 36 weeks (range, 31-38 weeks) and the mean birth weight was 2811g (range, 2050-3700g). One premature neonate developed respiratory distress and required ventilatory support at birth. In 7 neonates, clinical examination showed distended abdomen and emesis, whereas plain abdominal radiographs showed intestinal obstruction. All neonates underwent surgery and all had normal intestinal rotation, except one with total intestinal volvulus secondary to malrotation. Other causes of volvulus were suspected in 4 neonates: mesenteric defect (n=1), intestinal atresia (n=2) and narrow mesentery (n=1). Detorsion of total volvulus, ileostomy, or intestinal resection with primary anastomosis was performed in 2, 5, and 3 neonates, respectively. One patient with total intestinal volvulus secondary to malrotation died, whereas all other neonates survived. In one patient, the postoperative course was complicated by intestinal dysmotility of the distal small bowel requiring a secondary jejunoileostomy. Stoma closure was subsequently performed at 1 year of age with good outcome. One patient developed angiocholitis treated successfully with antibiotics. Median time to initiate enteral feeds was 7 days (range, 4-16 days) and all patients were subsequently weaned from parenteral nutrition. Median duration of parenteral nutrition was 29 days (range, 6-667 days). None of the patients had cystic fibrosis. Unlike postnatal volvulus, most prenatal volvulus occurs without malrotation. Although prenatal volvulus is a life-threatening condition, our results suggest that good long-term outcome can be achieved in most cases.

[Neonatal intoxication with pyrimethamine: risk due to the absence of pediatric formulation?]. / Intoxication néonatale à la pyriméthamine : un risque lié à l'absence de forme galénique pédiatrique ?

Curative treatment of congenital toxoplasmosis is based on the association of pyrimethamine and sulfonamide. There is currently no pediatric galenic formulation. We report the case of a newborn child affected by asymptomatic congenital toxoplasmosis who received an overdose of pyrimethamine. The patient received a dose of pyrimethamine 4 times, equal to 100 times the recommended dose, due to an error in the prescription. He had partial seizures 48 h after the last medicinal absorption. We noted a lack of appetite and vomiting, with a favorable progression in 5 days. Blood analysis showed isolated, spontaneously regressive moderate cholestasis. We propose a pharmacological clarification on the treatment of congenital toxoplasmosis.

[Neonatal seizures, buprenorphine abstinence syndrome, and substitutive treatment with morphine]. / Convulsions néonatales, syndrome de sevrage à la buprénorphine et traitement morphinique substitutif.

We report the case of a hypotrophic twin who presented neonatal abstinence syndrome to buprenorphine and developed neonatal seizures when the substitutive treatment by morphine was stopped. The other eutrophic twin did not develop withdrawal symptoms. This case demonstrates the unpredictable nature of transplacental transfer of buprenorphine. It also shows that neonatal abstinence syndrome can be potentially severe and that morphine treatment is not without risk.

[Fetal and neonatal complications of gestational diabetes: perinatal mortality, congenital malformations, macrosomia, shoulder dystocia, birth injuries, neonatal outcomes]. / Complications foetales et néonatales du diagnostic gestationnel: mortalité périnatale, malformations congénitales, macrosomie, dystocie des épaules, traumatisme obstétrical, complications néonatales.

OBJECTIVE: To evaluate perinatal outcomes in case of gestational diabetes (GD) treated or not. METHODS: This study is based on Pubmed search and on NICE and HAS recommendations. RESULTS: Moderate or severe GD increases the risk of foetal and neonatal complications [EL1]. The risk of malformation is slightly increased in case of GD compared with non diabetic population [EL2]. The increased risk of malformation is probably linked to undiagnosed cases of type 2 diabetes among cases of GD [EL2]. There is a continuous association of maternal glucose levels with increased birth weight [EL2]. The incidence of macrosomia decreases when diabetes is treated [EL1]. Data from the literature don't allow estimating precise risk of hypertrophic cardiomyopathy in case of GD, but severe clinical form is exceptional. Risk of neonatal asphyxia and perinatal death is not increased in case of GD [EL2]. Birth injuries and nerve palsy are rare in case of GD, and there is no evidence for increased incidence of such events when GD is not treated. The risk of neonatal respiratory distress whatever is the cause, is difficult to estimate. There is no evidence to establish a link between GD and neonatal respiratory distress. It is difficult to estimate the risk of neonatal hypoglycaemia because of various definitions used in the different studies, but the frequency of hypoglycaemia treated with IV glucose is low [EL1]. The risk of hypocalcemia [EL4] and hyperbilirubinemia [EL1] is similar to that of the general population. CONCLUSION: Severe perinatal complications specifically linked to GD are rare. Macrosomia is the principal neonatal adverse outcomes demonstrated in case of GD. It is the main factor related to the complications reported in case of GD. Maternal obesity is an additional risk factor of neonatal adverse outcomes and is independent from the diabetes.

[Management of neonates born to mothers with gestational diabetes: paediatric environment]. / Particularités de la prise en charge du nouveau-né de mère avec diabète gestationnel. Environnement pédiatrique.

OBJECTIVE: To estimate the modalities of neonatal care for newborn from mother with gestational diabetes (GD) treated or not. METHODS: This study is based on Pubmed search and on NICE and HAS recommendations. RESULTS: There is no paediatric indication to organize the birth in a specialized structure, excepted in case of severe abnormality of the foetal growth, of severe malformation or of risk of prematurity. It is recommended to watch systematically the glycaemia of the newborn children of mother with GD treated by insulin or in case of macrosomia or growth restriction. The systematic surveillance of the glycaemia is not indicated at the child's of mother with GD treated by only diet and without abnormality of growth. The newborn should benefit from the usual surveillance of the neonatal icterus. The dosage of the calcemia and the realization of blood cells count are indicated according to the clinical signs. The realization of additional examinations in search of a cardiac, osseous or cerebral malformation must be directed according to the signs in the clinical examination. The indications of transfer of the newborn of mother with DG in neonatal unit are the same that for every newborn child. CONCLUSIONS: The newborn can be welcomed in the maternity of nearness except in case of prematurity, of severe malformations or of severe abnormality of the foetal growth. The care of the newborn of mother with DG, in particular for the prevention, the detection and the treatment of hypoglycaemias, will be improved by the existence of a protocol.

Management of infants born to mothers with gestational diabetes. Paediatric environment.

OBJECTIVE: To evaluate the modalities of neonatal care for cases of treated and untreated gestational diabetes mellitus (GDM). METHODS: A search of the PubMed database was performed and recommendations from the National Institute for Health and Clinical Excellence and the French National Authority for Health were consulted. RESULTS: There were no paediatric indications for birth to take place in a specialised facility, except in cases of severe foetal growth abnormality, major malformations or risk of premature birth. Systematic blood glucose monitoring is recommended for newborns of mothers with insulin-treated GDM, or infants considered large or small for gestational age. Systematic blood glucose monitoring is not recommended for infants of mothers with diet-controlled GDM, or in the absence of growth abnormalities. Newborns should undergo routine neonatal icterus monitoring. Measurement of calcium levels and a complete blood count (CBC) should be carried out when clinically appropriate. Complementary testing for the detection of heart, bone or brain defects should be performed according to clinical signs. The indications for transferring infants of mothers with GDM to a neonatal intensive care unit are the same as for all other newborns. CONCLUSIONS: Newborns can be cared for in general maternity wards, except in cases of premature birth, major malformations or severe foetal growth abnormalities. The management of newborns of mothers with GDM, particularly in the prevention, detection and management of hypoglycaemia, is improved through the existence of a written protocol.

Foetal and neonatal complications in gestational diabetes: perinatal mortality, congenital malformations, macrosomia, shoulder dystocia, birth injuries, neonatal complications.

OBJECTIVE: To evaluate the risks of perinatal complications in infants born to mothers with treated or untreated gestational diabetes mellitus (GDM). METHODS: A search of the PubMed database was performed and recommendations from NICE and the French National Authority for Health were consulted. RESULTS: Untreated moderate or severe GDM increases the risk of foetal and neonatal complications (EL1). The risk of malformations slightly increases in newborns of mothers with GDM compared to the general population (EL2). This risk is probably associated with the presence of undiagnosed type 2 diabetes among patients with GDM (EL2). There is a linear relationship between maternal blood glucose levels and an increased birth weight (EL2). Treatment for GDM reduces the incidence of macrosomia (EL1). Although the risk of cardiomyopathy in cases of GDM cannot be accurately estimated based on the available data, severe clinical forms are rare. The risks of neonatal asphyxia and perinatal mortality are no higher in infants born to women with GDM (EL2). Birth injuries and brachial plexus injuries are rare, and no more likely to occur in cases of untreated GDM. It is difficult to assess the risk of respiratory distress, regardless of its cause. It is not possible to establish a link between GDM and neonatal respiratory problems due to insufficient data. Although the risk of neonatal hypoglycaemia is difficult to determine due to the variable definitions reported in the literature, the incidence of hypoglycaemia requiring intravenous therapy is low (EL1). The risks of hypocalcaemia (EL4) and hyperbilirubinemia (EL1) are similar to the general population. CONCLUSION: Serious perinatal complications specifically associated with GDM are rare. Macrosomia has been demonstrated to be the predominant adverse outcome in cases of GDM. It is the main factor linked to reported cases of complications in GDM. Maternal obesity is an additional risk factor for complications, regardless of diabetes status.

[Description and investigation of an outbreak of extended-spectrum beta-lactamase producing Escherichia coli strain in a neonatal unit]. / Description et investigation d'une épidémie nosocomiale de colonisations et d'infections à Escherichia coli producteur d'une bêta-lactamase à spectre étendu dans un service de néonatologie.

An outbreak of colonization and infection with an Escherichia coli strain producing extended-spectrum beta-lactamase (ESBL) occurred in a neonatal unit : a high rate of cases was observed, 27/59 neonates were colonized : one of them developed meningitis with favourable outcome and another baby developed conjunctivitis. Despite intensive efforts to control the outbreak by standard methods of hand hygiene, patients screening and isolation, the spread was uncontrolled and the unit was closed to all admission in order to stop the outbreak. The investigation was not able to identify a single outbreak's source. Emergence and spread of ESBL producing E. coli strains from community and hospital acquired infections are a significant public health problem with difficult choice of treatment for serious infections.