Transcatheter closure of hemodynamic significant patent ductus arteriosus in 32 premature infants by amplatzer ductal occluder additional size-ADOIIAS.

OBJECTIVES: The advent of Amplatzer Duct Occluder II additional Size (ADOIIAS) provided the potential to close hemodynamic significant patent ductus arteriosus (HSPDA) and to analyze the feasibility, safety and efficacy of the device. BACKGROUND: Treatment of a patent ductus arteriosus (PDA) in very premature neonates is still a dilemma for the neonatalogist who has to consider its significance and has to choose among different treatment options. Because surgical ligation and medical therapy both have their drawbacks, interventional catheterization might provide an alternative means of closing HSPDA. MATERIAL AND METHODS: Between September 2013 and June 2015, 32 premature infants with complications related to HSPDA defined by ultrasound (US) underwent transcatheter closure. The procedure was performed in the catheterization laboratory by venous cannulation without angiography. The position of the occluder was directed by X-ray and US. In particular we looked at procedural details, device size selection, complications, and short and mid-term outcomes. RESULTS: Thirty two premature infants, all of whom had clinical complications related to HSPDA, born at gestational ages ranging between 23.6 and 36 weeks (mean ± standard deviation 28 ± 3 weeks) underwent attempted transcatheter PDA closure using the ADOIIAS. Their mean age and weight at the time of procedure was 25 days (range 8-70 days) and 1373 g (range 680-2480 g), respectively. Ten infants weighed ≤1,000g. All ducts were tubular. The mean PDA and device waist diameters were 3.2 ± 0.6mm (range 2.2-4) and 4.4 ± 0.6 mm, respectively, and the mean PDA and device lengths 5.2 ± 2.0 mm (range 2-10) and 3.4 ± 1.3 mm. Median fluoroscopy and procedural times were 11 min (range 3-24) and 28 min (range 10-90), respectively. Complete closure was achieved in all but one patient. There was no device migration. A left pulmonary artery (LPA) obstruction developed in one patient. Five infants died. Four deaths were related to complications of prematurity and one death in a 680 g infant was related to the procedure. CONCLUSIONS: It is feasible to close HSPDA in relative safety in premature infants who have severe and complex disease. Success requires perfect selection of the occluder and exact positioning by US. © 2017 Wiley Periodicals, Inc.

Increased MMP-9 and TIMP-1 in mouse neonatal brain and plasma and in human neonatal plasma after hypoxia-ischemia: a potential marker of neonatal encephalopathy.

INTRODUCTION: To implement neuroprotective strategies in newborns, sensitive and specific biomarkers are needed for identifying those who are at risk for brain damage. We evaluated the effectiveness of matrix metalloproteinases (MMPs) and their naturally occurring tissue inhibitors of metalloproteinases (TIMPs) in predicting neonatal encephalopathy (NE) damage in newborns. RESULTS: Plasma MMP-9 and TIMP-1 levels were upregulated as early as 1 h after the HI insult but not did not show such elevations after other types of injury (ibotenate-induced excitotoxicity, hypoxia, lipopolysaccharide-induced inflammation), and brain levels reflected this increase soon thereafter. We confirmed these results by carrying out plasma MMP-9 and TIMP-1 measurements in human newborns with NE. In these infants, protein levels of MMP-9 and TIMP-1 were found to be elevated during a short window up to 6 h after birth. DISCUSSION: This feature is particularly useful in identifying newborns in need of neuroprotection. A second peak observed 72 h after birth is possibly related to the second phase of energy failure after a HI insult. Our data, although preliminary, support the use of MMP-9 and TIMP-1 as early biomarkers for the presence and extent of perinatal brain injury in human term newborns. METHODS: We first used a mouse model of neonatal HI injury to explore mechanistic aspects such as the time course of these markers after the hypoxia-ischemia event, and the correlation between the levels of these candidate markers in brain and plasma.

Acute post-streptococcal glomerulonephritis in children of French Polynesia: a 3-year retrospective study.

The aim of this study was to define the current demographic, clinical and prognostic characteristics of acute post-streptococcal glomerulonephritis (APSGN) in French Polynesia and to compare these features with those of other populations. Fifty children, all of whom were <15 years old and had been admitted to the Territorial Hospital of Papeete for APSGN between January 2005 and December 2007, were retrospectively enrolled in the study. Diagnostic criteria were microscopic or macroscopic haematuria, decreased C3 fraction of the complement and evidence of recent streptococcal infection. The annual incidence was 18 cases per 100,000 children <15 years of age in 2007. Most of the children (98%) enrolled in the study were of Polynesian ethnic origin, 27 were male (54%), and the average age at presentation was 6.7 years. Signs of previous respiratory infections were clearly evident in 40% of the children. Most of the patients presented during the rainy season, correlating with the relatively high incidence of skin infections at this time. The majority of patients had proteinuria (98%), with 25% having proteinuria in the nephrotic range (proteinuria/urinary creatinine >3 g/g). The presentation was severe in 22% of the children (congestive cardiac failure, severe hypertension and/or encephalopathy), and renal failure was an initial presenting symptom in 43.7%. The C3 fraction was lower in severe presentations, but the type of haematuria, level of proteinuria and inflammatory syndrome were not correlated with immediate severe forms or with initial renal failure. Haematuria resolved in a mean of 7.7 months and proteinuria in a mean of 3.9 months. None of the children had hypocomplementemia for more than 8 weeks. Acute post-streptococcal glomerulonephritis is endemic among French Polynesians, and they can be considered to be a high-risk population. Despite a high incidence of skin infections, however, the predominance of respiratory infections potentially indicates that French Polynesia is on the way to become a low-incidence area. Systematic detection and treatment of group A Streptococcus should be intensified.

Transcatheter occlusion of the patent ductus arteriosus in premature infants weighing less than 1200 g.

OBJECTIVES: Over the last few decades different strategies have been proposed to treat persistent ductal patency in premature infants. The advent of the Amplatzer Duct Occluder II Additional Size (ADOIIAS) provided the potential to close the patent ductus arteriosus (PDA). Opinions differ on the significance and treatment of PDA in premature neonates. Because surgical ligation and medical therapy both have their drawbacks, interventional catheterisation can be considered as an alternative means of closing the ductus arteriosus. Our aim was to analyse the feasibility, safety and efficacy of this device in premature infants weighing <1200 g at procedure. METHODS: Eighteen premature infants underwent transcatheter closure. The procedure was performed in the catheterisation laboratory by venous cannulation without angiography. The position of the occluder was directed by X-ray and ultrasound. We looked at procedural details, device size selection, complications and short-term and mid-term outcomes. RESULTS: Eighteen infants born at gestational ages ranging between 23.6 and 29+6 weeks (mean±SD 25+6±3 weeks) underwent transcatheter PDA closure. Their mean age and weight at the time of the procedure was 20 days (range 8-44 days) and 980 g (range 680-1200 g), respectively. The mean PDA and device waist diameters were 3.2±0.6 mm (range 2.2-4 mm) and 4.5±0.6 mm, respectively, and the mean PDA and device lengths were 4.3±1.2 mm (range 2-10 mm) and 2.5±0.9 mm, respectively. Complete closure was achieved in all but one patient. There was no device migration. One patient developed a left pulmonary artery obstruction. Three infants died. Two deaths were related to complications of prematurity and one to the procedure. CONCLUSIONS: Transcatheter closure of a PDA is feasible in very low weight infants with ADOIIAS and is an alternative to surgery. Success requires perfect selection and placement of the occluder.

Necrotic skin lesions and cerebral infarction in the newborn: two case reports.

Localized skin necrosis with deeper soft tissue injury at birth is unusual and has been rarely reported in association with cerebral infarction. Two cases with forearm necrotic skin associated with injured deeper soft tissue are described in which brachial artery thrombosis was documented. Considering the possibility of disseminated thrombosis, cerebral ultrasound showed brain infarction due to unilateral middle cerebral artery thrombosis on Doppler. The origin of the embolism was identified in the inferior vena cava and umbilical and portal vein. No thrombophilia or other risk factors were identified. The various causes of the cutaneous lesions pointed to an antenatal process whose etiology and mechanisms are discussed. Localized necrotic skin lesions must be considered as part of a systemic embolic process and can lead to extensive especially cerebral ultrasound exploration.

Low species diversity and high interindividual variability in faeces of preterm infants as revealed by sequences of 16S rRNA genes and PCR-temporal temperature gradient gel electrophoresis profiles.

Little information regarding the composition of the gut microbiota in preterm infants is available. The purpose of this study was to investigate the bacterial diversity in faeces of preterm infants, using analysis of randomly cloned 16S rRNA genes and PCR-TTGE (temporal temperature gradient gel electrophoresis) profiles, to determine whether noncultivated bacteria represented an important part of the community. The 288 clones obtained from faecal samples of 16 preterm infants were classified into 25 molecular species. All but one molecular species had a cultivated representative in public databases: molecular tools did not reveal any unexplored diversity. The mean number of molecular species per infant was 3.25, ranging from one to eight. There was a high interindividual variability. The main groups encountered were the Enterobacteriaceae family and the genera Enterococcus, Streptococcus and Staphylococcus. Seven preterm infants were colonized by anaerobes and only four by bifidobacteria. TTGE profiles were composed of one to nine bands (mean value: 4.3). Furthermore, 51 of 59 clones (86%) comigrated with a band of the corresponding faecal sample. This study will form a comparative framework for other studies, e.g. on the faecal microbiota of preterm infants with different pathologies or the impact of diet on colonization.

Midbrain disconnection: an aetiology of severe central neonatal hypotonia.

A full term girl exhibited massive hypotonia related to severe posterior fossa abnormalities consisting of pontocerebellar hypoplasia with midbrain disconnection. The latter was due to lack of one and marked hypoplasia of the other cerebral peduncles. In addition, there was mild vermian and cerebellar hypoplasia. Compared to usual pontocerebellar hypoplasia, the midbrain disconnection is a distinctive feature of our case. It is a rare malformation only three similar cases have previously been described.

Familial rectal pain: a familial autonomic disorder as a cause of paroxysmal attacks in the newborn baby.

A 2-day-old baby exhibited impressive paroxysmal attacks consisting of bradycardia, bronchospasm and vasomotor fits (Harlequin type) related to a rare, dominantly inherited form of dysautonomy called "familial rectal pain". These events were recurrently triggered by emotion, diaper changes or wiping of the perineal areas or eating. Sometimes they occurred spontaneously. Carbamazepine had an excellent effect on the fainting. At four years of age, the child had normal psychomotor development with only minimal symptoms, and very rare paroxysmal attacks. The father of the child has minimal symptoms of this entity, with essentially ocular manifestations. Familial rectal pain is a very rare entity that must always be considered as a possible aetiology of any life-threatening event in an infant because of the availability of a very effective treatment. The existence of minimal forms of familial rectal pain is possible, and it is likely that this entity is underdiagnosed. [Published with video sequences].

Survival and morbidity of preterm children born at 22 through 34 weeks' gestation in France in 2011: results of the EPIPAGE-2 cohort study.

IMPORTANCE: Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines. OBJECTIVES: To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997. DESIGN, SETTING, AND PARTICIPANTS: The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011. MAIN OUTCOMES AND MEASURES: Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3). RESULTS: A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks. CONCLUSIONS AND RELEVANCE: The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.

Neonatal acute renal failure secondary to maternal exposure to telmisartan, angiotensin II receptor antagonist.

Fetal and neonatal toxic effects of angiotensin II receptor antagonists have been described in animals and humans. Five cases of fetal or neonatal deaths have been reported following maternal use of sartans for hypertension. We report a case of neonatal transient renal failure following telmisartan therapy during pregnancy. This class of antihypertensive drugs should be avoided during pregnancy and breastfeeding.

Report on 3 patients with 12p duplication including GRIN2B.

The duplication of the short arm (p) of chromosome 12 is a rare chromosomal abnormality, and most reported cases result from malsegregation of a balanced parental translocation associated with other chromosomal imbalances. Of the reported cases, only 15 involve a pure and complete 12p duplication and only 10 involve a pure and partial duplication overlapping the 12p12.3p13.1 region, including a single instance of an inherited duplication in two related individuals. Here, we report three new patients with a pure 12p duplication, detected by conventional cytogenetic studies and characterized by array-comparative genomic hybridization (array-CGH) and fluorescence in situ hybridization (FISH). The first patient was a child carrying a de novo inverted duplication of the short arm of chromosome 12. His phenotype was similar to that of the "trisomy 12p syndrome", characterized by developmental delays and craniofacial abnormalities including a high forehead, a short nose with anteverted nostrils and an everted lower lip. The second and third patients were a mother and son with a direct 12p12.3p13.1 duplication, exhibiting a milder phenotype characterized by moderate developmental delays, dysmorphic facial features, behavioral problems and obesity. The present data, including the rarity of the familial cases, should contribute to our knowledge of the genotype/phenotype correlation in trisomy 12p patients.

Outcome of cerebellar injury in very low birth-weight infants: 6 case reports.

Cerebellum injury is a severe and underestimated complication in very low birth-weight infants. Six cases of extreme premature babies are reported: 3 of them died during the neonatal period; the other 3 survived with severe neurological disabilities. Microcephaly, strabismus, and severe developmental delay without major motor handicap are very peculiar for the preterm in the long-term outcome. Easy diagnosis is possible by specific ultrasound windows and early diagnosis is required regarding the possible severe prognosis and to organize precisely the follow-up.

Physiopathology hypotheses and treatment of pulmonary sequestration.

Illustrated by this case report, partial obstruction of the venous collector of extrapulmonary sequestration explains pleural effusion and fetal hydrops. Therapy requires fetal thoracentesis and neonatal arterial occlusion of the pedicle artery allowing uneventful follow-up.