Management of neonatal spontaneous intestinal perforation by peritoneal needle aspiration.

OBJECTIVE: To describe conservative management of spontaneous intestinal perforation (SIP) in preterm infants using peritoneal needle aspiration (PNA). STUDY DESIGN: Monocentric retrospective review of SIP cases treated primarily by PNA between 1999 and 2015 (n=31). RESULTS: Mean gestational age was 29.2±2.4 weeks and birthweight 1149±428 g. SIP occurred at 3.7±2.2 days of life. PNA achieved definitive treatment in 18 patients (60%) with a mean of 1.8 (±0.8) procedures. All patients requiring more than three PNAs had secondary laparotomy. Two patients died and five presented severe cerebral lesions. Full enteral feeding was achieved 42±18 days after SIP. Intestinal morbidity included cholestasis (n=6), intestinal stricture (n=1) and growth restriction (n=22). On follow-up (n=25, median=4 years), no severe impairment was noted. Seventeen children (68%) had a normal development. CONCLUSION: PNA as primary therapy for SIP is a viable option, resulting in definitive treatment in 60% of cases, with limited mortality and morbidity.

Xq28 duplication including MECP2 in six unreported affected females: what can we learn for diagnosis and genetic counselling?

Duplication of the Xq28 region, involving MECP2 (dupMECP2), has been primarily described in males with severe developmental delay, spasticity, epilepsy, stereotyped movements and recurrent infections. Carrier mothers are usually asymptomatic with an extremely skewed X chromosome inactivation (XCI) pattern. We report a series of six novel symptomatic females carrying a de novo interstitial dupMECP2, and review the 14 symptomatic females reported to date, with the aim to further delineate their phenotype and give clues for genetic counselling. One patient was adopted and among the other 19 patients, seven (37%) had inherited their duplication from their mother, including three mildly (XCI: 70/30, 63/37, 100/0 in blood and random in saliva), one moderately (XCI: random) and three severely (XCI: uninformative and 88/12) affected patients. After combining our data with data from the literature, we could not show a correlation between XCI in the blood or duplication size and the severity of the phenotype, or explain the presence of a phenotype in these females. These findings confirm that an abnormal phenotype, even severe, can be a rare event in females born to asymptomatic carrier mothers, making genetic counselling difficult in couples at risk in terms of prognosis, in particular in prenatal cases.

Evaluation of the management of pregnancies and infants at risk for congenital syphilis: La Réunion, 2008 to 2014.

OBJECTIVE: To evaluate the maternal-fetal management and follow-up of infants at risk for congenital syphilis. STUDY DESIGN: Monocentric retrospective cohort study at the Félix Guyon Hospital, Saint-Denis, La Réunion between January 2008 and December 2014. Management of 38 pregnancies (35 women, 39 fetuses) with a positive syphilis serology was evaluated according to the Centers for Disease Control and Prevention (CDC) guidelines. RESULTS: A total of 68% (n=26) of pregnancies were screened before 16 weeks of gestation, and 26% (n=10) had appropriate treatment. Adverse outcomes were noted in 45% of pregnancies. Neonatal serology was not performed in 7 live-born neonates (19%) and 33 infants were classifiable according to the four CDC scenarios. In the infants, adequate complementary evaluation and appropriate treatment were noted in 42% (n=13) and 55% (n=17) of cases, respectively. Rate of infant follow-up was 76% (n=16). No treatment failure was observed in infants. CONCLUSION: Reinforcement of public health policies and a better sensitization, training and collaboration among perinatal caregivers are warranted given the gaps revealed in our study.

Antenatal presentation of hereditary lymphedema type I.

Fetal edema can present as limited subcutaneous edema, fluid accumulation in body cavities or hydrops fetalis. Hydrops fetalis is the end stage of a variety of fetal/maternal disorders and nonimmune etiology represents more than 3/4 of cases. Lymphatic dysplasia may account for a subset of patients with nonimmune and "idiopathic" hydrops fetalis, fetal chylous ascites or chylothorax. We present two unrelated patients with antenatal features of hereditary lymphedema syndrome, in whom Milroy disease was diagnosed after birth. At least, 20 genes have been identified to cause primary lymphedema, with sometimes antenatal features. Hereditary lymphedema syndrome should be considered in cases of nonimmune hydrops fetalis/fetal edema after ruling out the more common etiologies.

Molecular findings and clinical data in a cohort of 150 patients with anophthalmia/microphthalmia.

Anophthalmia and microphthalmia (AM) are the most severe malformations of the eye, corresponding respectively to reduced size or absent ocular globe. Wide genetic heterogeneity has been reported and different genes have been demonstrated to be causative of syndromic and non-syndromic forms of AM. We screened seven AM genes [GDF6 (growth differentiation factor 6), FOXE3 (forkhead box E3), OTX2 (orthodenticle protein homolog 2), PAX6 (paired box 6), RAX (retina and anterior neural fold homeobox), SOX2 (SRY sex determining region Y-box 2), and VSX2 (visual system homeobox 2 gene)] in a cohort of 150 patients with isolated or syndromic AM. The causative genetic defect was identified in 21% of the patients (32/150). Point mutations were identified by direct sequencing of these genes in 25 patients (13 in SOX2, 4 in RAX, 3 in OTX2, 2 in FOXE3, 1 in VSX2, 1 in PAX6, and 1 in GDF6). In addition eight gene deletions (five SOX2, two OTX2 and one RAX) were identified using a semi-quantitative multiplex polymerase chain reaction (PCR) [quantitative multiplex PCR amplification of short fluorescent fragments (QMPSF)]. The causative genetic defect was identified in 21% of the patients. This result contributes to our knowledge of the molecular basis of AM, and will facilitate accurate genetic counselling.

[Prevalence, severity, and predictors of bronchopulmonary dysplasia in a cohort of very preterm infants]. / Prévalence, gravité et facteurs prédictifs de la dysplasie bronchopulmonaire dans une cohorte ultramarine de grands prématurés.

OBJECTIVES: The aim of this retrospective cohort study was to determine the prevalence and severity of BPD and its predictors in a regional cohort of very preterm (VP) infants in Reunion Island. METHODS: All autochthonous VP infants, live-born before the 33rd week of gestation (WG) between 1st January 2008 and 31st December 2009, were eligible for the study. Only VP infants surviving at least 28 days, for whom the parameters were known from birth, were included in the case-control study of predictors of moderate to severe BPD (BPDmo/s). RESULTS: In VP infants less than 33 WG, the rate of overall BPD (3 grades of severity) was 30.7%. Among those who survived 28 days or more, the rate of BPDmo/s was 13.1% (95%CI: 10.2-15.9%). In VP infants less than 32 WG that survived at 36 WG, the prevalence of BPDmo/s was 18.2% (95% CI: 14.2-22.1%). In a fixed-effect logistic model, adjusted for gestational age, postnatal growth, and the mode of ventilation at 24h, 4 key factors were predictive of BDPmo/s: small for gestational age, surfactant, delayed energy intake, and late-onset neonatal infection. In a mixed-effect logistic model adjusted for these same cofactors, the site was associated with BPDmo/s, in line with a center-effect. CONCLUSION: The prevalence of BPDmo/s in the mixed-race population of Reunion Island is consistent with those observed in Europe but were site-specific. In our setting, predictors of individual BPDmo/s are similar to those already identified.

[About six observations of double discrepancy of the heart: feasibility of prenatal diagnosis?]. / À propos de six observations de double discordance cardiaque : faisabilité du diagnostic anténatal ?

The double discrepancy (DD) is an exceptional cardiopathy, manifested by atrioventricular and ventriculo-arterial discordances. DD is rarely diagnosed in the antenatal period and is often found in adults when cardiac complications occur. We describe six cases of DD, the different forms, their ultrasound semiology, and the assessment of prognosis, correlated with the existence of associated cardiac anomalies.

[Severe forms of chikungunya virus infection in a pediatric intensive care unit on Reunion Island]. / Infections graves a virus chikungunya en réanimation pédiatrique a l'ile de La Réunion.

UNLABELLED: In 2005-2006, an unexpected, massive outbreak of chikungunya occurred on Reunion Island, a French overseas territory in the Indian Ocean. This arboviral infection transmitted by a mosquito of the Aedes genus is usually benign. A surprising feature of the Reunion Island epidemic was the occurrence of rare severe forms involving adults as well as children. OBJECTIVES: The purpose of this report is to describe severe forms of chikungunya observed in children hospitalized in a pediatric intensive care unit. PATIENTS AND METHODS: This retrospective single-center study was conducted from January 1st to April 30th, 2006. Children between 1 month and 15 years admitted to the pediatric intensive care unit with proven chikungunya infection were included. RESULTS: A total of 9 children were included. The main manifestations were extensive skin blisters in 5 cases, neurological symptoms (encephalopathy) in 4, cardiac complications (myocarditis, hemodynamic disorders) in 5 and bleeding in 1. Two children died. The causes of death were circulatory failure associated with coma and massive hemorrhage in one case and post-infectious encephalitis in the other. Three survivors present long-term neurologic or dermatologic sequels. DISCUSSION: Severe cases of chikungunya in children provide a stark reminder of the cardiac and neurological tropism of the virus and its hemorrhagic forms with high potential mortality and morbidity. These cases underline the need for personal protection measures and for research to develop specific antiviral therapy and vaccines to prevent potentially lethal forms of the disease.

Giant hepatic cysts: prenatal findings and uncommon postnatal outcome.

With modern prenatal imaging, liver cysts are being diagnosed more often. Although large cysts are usually asymptomatic, they may present as an abdominal emergency requiring surgery in the first weeks of life. We report a series of 3 patients with prenatal diagnosis of isolated cystic liver lesions diagnosed at 22, 31 and 33 weeks of gestational age. The hepatic origin of the cysts was confirmed prenatally by a MRI in 2 cases, with visualization of a normal gallbladder. The prenatal course was uneventful. Postnatal ultrasound confirmed the diagnosis of liver cyst, showed normality of the biliary tract and in one case, rupture of the cyst during delivery. Because of an uncommon rapid increase in size, the 3 children underwent surgical excision of the cysts within the first weeks of life. These were non-bile-containing intrahepatic cysts arising from segment IV. Long-term follow up was uneventful.

Tibial developmental field defect in valproic acid embryopathy: Report on three cases.

Prenatal exposure to valproic acid (VA) is associated with an increased risk of congenital malformations, especially limb defects like radial ray defects. Tibial developmental field defect in VA embryopathy remains exceptional. We report on three patients presenting with tibial hypo/aplasia associated with either femoral bifurcation or radial ray defect following prenatal exposure to VA. Femoral bifurcation and tibial agenesis has been described in the Gollop-Wolfgang complex and in the tibial agenesis-ectrodactyly syndrome. Tibial agenesis has also been reported in VACTERL association. The relation between prenatal exposure to VA and tibial agenesis is discussed.

Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations.

OBJECTIVE: To determine the spectrum of clinical, neuropsychological, and neuroradiologic features in patients with autosomal recessive primary microcephaly (MCPH) due to ASPM gene mutations. METHODS: ASPM was sequenced in 52 unrelated MCPH probands. In patients with ASPM mutations, we evaluated the clinical phenotype, cognition, behavior, brain MRI, and family. RESULTS: We found homozygous or compound heterozygous ASPM loss-of-function mutations in 11 (22%) probands and 5 siblings. The probands harbored 18 different mutations, of which 16 were new. Microcephaly was severe after 1 year of age in all 16 patients, although in 4 patients the occipital-frontal circumference (OFC) at birth was decreased by only 2 SD. The OFC Z score consistently decreased after birth. Late-onset seizures occurred in 3 patients and significant pyramidal tract involvement in 1 patient. Intellectual quotients ranged from borderline-normal to severe mental retardation. Mild motor delay was noted in 7/16 patients. Language development was delayed in all patients older than 3 years. Brain MRI (n = 12) showed a simplified gyral pattern in 9 patients and several malformations including ventricle enlargement (n = 7), partial corpus callosum agenesis (n = 3), mild cerebellar hypoplasia (n = 1), focal cortical dysplasia (n = 1), and unilateral polymicrogyria (n = 1). Non-neurologic abnormalities consisted of short stature (n = 1), idiopathic premature puberty (n = 1), and renal dysplasia (n = 1). CONCLUSIONS: We provide a detailed description of features associated with ASPM mutations. Borderline microcephaly at birth, borderline-normal intellectual efficiency, and brain malformations can occur in ASPM-related primary hereditary microcephaly.

[Chikungunya in paediatrics: epidemic of 2005-2006 in Saint-Denis, Reunion Island]. / Aspects pédiatriques de l'épidémie de Chikungunya à l'île de la Réunion.

UNLABELLED: During the southern-hemispheric 2005-2006 summer, Reunion Island was struck by an epidemic of Chikungunya (Chik), which affected more than a third of the overall population. OBJECTIVES: Our objective was to describe pediatric cases of Chick. MATERIAL AND METHODS: We conducted a retrospective descriptive monocentric study of confirmed pediatric cases of Chik recruited at Saint-Denis' departmental hospital during the peak of the epidemic (January 1st to April 30th 2006). RESULTS: Eighty-six children aged 10 days to 18 years were included. In addition to the typical clinical presentation, we observed other phenotypes. Well-known complicated forms with neurologic, cardiac, gastro-intestinal (plus dehydration) involvement were thoroughly investigated using modern medical technology. We observed 2 fatal cases of acute disease in 9-year-old children: death resulted from a central nervous system insult in one case, and multisystemic neurological, cardiac, haemorrhagic involvement in another. Severe acute presentations requiring hospital admission involved mainly children aged less than 6 months, and those with cardiac, skin and neurologic impairment. The study identified 3 cases of epidermolysis bullosa, which to our knowledge, have never been described previously. CONCLUSION: Chik in children warrants further research in order to propose early and appropriate treatments to avoid complications.

[Fryns syndrome. Report on 3 new cases]. / Syndrome de Fryns. Présentation de 3 nouvelles observations.

BACKGROUND: Fryns syndrome is a lethal autosomal recessive syndrome which includes congenital diaphragmatic hernia (CDH), pulmonary hypoplasia, cranio-facial manifestations including a coarse face, a cleft palate / lip and cloudy corneae, distal limb hypoplasia and internal malformations including central nervous system, cardiovascular, gastrointestinal, urogenital and skeletal anomalies. CASES REPORT: We report on 3 patients with Fryns syndrome in the french Indian Ocean islands (La Réunion and Mayotte islands). Pregnancies were complicated by polyhydramnios. All patients had coarse face, cloudy corneae, cleft lip / palate or high-arched palate, hypoplastic nails and brachytelephalangy. They died in the neonatal period. Two had CDH and 1 did not have a diaphragmatic involvement but a severe respiratory distress syndrome with refractory hypoxemia. Cytogenetic studies of blood lymphocytes and skin fibroblasts were normal. CONCLUSIONS: Fryns syndrome is the most common multiple congenital anomaly associated with CDH. The diagnosis is strongly suggested when CHD and brachytelephalangy are associated. Phenotypes with CDH similar to Fryns syndrome have been described with cytogenetic aberrations with G-banded chromosome analysis and submicroscopic chromosome deletions detected by high resolution karyotyping or array comparative genomic hybridization (CGH). Exclusion of chromosome aberrations (including isochromosome 12p in skin fibroblasts) is needed prior to making the diagnosis of Fryns syndrome. In sporadic cases, high resolution karyotyping or array CGH should be performed for correct diagnosis and genetic counselling.

Bruck syndrome: second antenatal diagnosis.

Bruck syndrome is characterized by the association of arthrogryposis and osteogenesis imperfecta. It is a distinct autosomal recessive disorder associated with normal collagen I. The main features are osteoporosis, long bone bowing and scoliosis due to vertebral deformities and congenital joint contractures. We describe a French girl who was born with ankle and wrist contractures (second antenatal discovery).

Maxillo-nasal dysplasia (binder syndrome): antenatal discovery and implications.

Binder syndrome (BS) or maxillo-nasal dysplasia is an uncommon developmental anomaly affecting primarily the anterior part of the maxilla and nasal complex. The characteristic findings are a failure of development in the premaxillary area with associated deformities of the nasal skeleton and the overlying soft tissues. Affected individuals typically have an unusually flat, underdeveloped midface (midfacial hypoplasia), with an abnormally short nose and flat nasal bridge, underdeveloped upper jaw, relatively protruding lower jaw and/or a 'reverse overbite' (or class III malocclusion). A case of BS was diagnosed at 24 weeks of gestation using two- and three-dimensional ultrasound. The first sign was an isolated flattened fetal nose in the mid-sagittal plane. Further ultrasound imaging showed the absence of the naso-frontal angle, giving impression of flat forehead and small fetal nose. We discuss about this entity.

[Primary amebic meningoencephalitis: 1st case observed in Madagascar]. / Méningo-encéphalite primitive à amibes libres: 1er cas observé à Madagascar.

The primary amebic meningoencephalitis is an acute suppurative infection that involves both the brain and the meninges. It is caused by Naegleria fowleri and is a very rare and fulminating condition, so far nearly always fatal. We report the first case in the area of Southern part of Indian Ocean that occured in a 7-year old French boy living in Madagascar. It is assumed that the disease was contracted by swimming in warm fresh water in a lake of the Madagascar east coast. Clinical signs began 10-12 days after exposure, associating headache, vomiting and pyrexia (39-40 degrees C). Upon admission in a Madagascar hospital, the patient was started on antibiotics, that did not control the disease and soon presented with a loss of consciousness and a delirium. He was transferred to Reunion island (Centre Hospitalier Départemental Félix-Guyon), where the diagnosis of primary amebic meningoencephalitis was confirmed. Therefore, he was started on high-dose of intraspinal amphotericin B, IV amphotericin B lipid complex and tetracycline. He developed myocarditis, diabetes insipidus, deep coma and subsequently died a week later. The diagnosis of amebic meningoencephalitis was based on: -- the cerebrospinal fluid examination that confirmed the diagnosis of purulent meningitis: 420 leucocytes (76% polynuclears, 14% lymphocytes), 90 red blood cells, and showed 50 ameboid trophozoites per 100 leucocytes, approximately 20 microm in size. -- the flagellate transformation test in distilled water showed two anterior flagellas that confirmed the genus Naegleria.

[Neonatal accidental burn by isopropyl alcohol]. / Brûlure néonatale accidentelle à l'isopropanol.

Antiseptic solutions are commonly used for skin care but are not always safe. In preterm infants, application of antiseptic solutions can lead to serious burns. We report the case of a premature newborn who developed severe burns at 35 weeks post-conceptional age, after his mother used disposable antiseptic towels containing isopropyl alcohol for his skin care. Burns outcome led to diffuse skin burn and death of the baby. Several cases of isopropyl alcohol poisoning through skin absorption have been reported in neonate and infants. Because of its neonatal toxicity, isopropyl alcohol has been excluded from composition of antiseptic solutions commonly used in neonatology. However, isopropyl alcohol is still available in many housecleaning and cosmetic products, while its toxic effects in children are not clearly mentioned. A specific mention "toxic for infants and children" should appear on mass consumption products containing isopropyl alcohol. Moreover, health workers may individually inform parents about possible hazards of poisoning through skin absorption.

Peritoneal needle suction for intestinal perforation in the preterm neonate.

UNLABELLED: A few years ago, most intestinal perforations in the premature newborn appeared within the clinical context of necrotising enterocolitis (NEC). Since then, we have observed an increase in the number of isolated perforations appearing outside typical NEC. The fact that the perforations are more often isolated, and the healing capabilities of the premature intestine, led us to propose peritoneal needle suction (PNS) alone as first treatment for intestinal perforations in the premature neonate. MATERIALS AND METHOD: The charts of 6 consecutive premature infants presenting with intestinal perforations treated initially by PNS alone were reviewed. RESULTS: The patients' median birth weight was 1030 g, with a median gestational age of 27 weeks. In 5 out of 6 infants (83 %), PNS achieved complete exsufflation without recurrence of the pneumoperitoneum and complete intestinal healing, allowing complete enteral feeding 30 to 71 days after perforation. One infant with recurrent pneumoperitoneum after 3 PNS and peritoneal drainage was operated. All infants survived. CONCLUSION: We believe that for early perforations of the premature neonate, the poor diffusion of the infection and the frequent capacity of the perforation to close and subsequently heal without scars, favour a minimally invasive management using PNS.

[Subependymal pseudocysts in the fetal brain revealing Zellweger syndrome]. / Pseudo-kystes subépendymaires au sein du cerveau foetal: découverte d'un syndrome de Zellweger.

Prognosis of subependymal pseudocyst is poor when associated with other anomalies. They can be caused by infectious, vascular, chromosomal or metabolic disorders but are rarely described in the antenatal period. We report the prenatal diagnosis of subependymal pseudocyst by MRI after prenatal detection of isolated ventriculomegaly at 23 weeks gestation. The karyotype was normal. The diagnostic of Zellweger syndrome was suspected and was confirmed after birth by metabolic studies. Metabolic studies with culture of chorionic villus cell is indicated for subsequent pregnancies.