Naziha Khen-Dunlop

Esophageal atresia: Data from a national cohort

PURPOSE A prospective national register was established in 2008 to record all new cases of live-birth newborns with esophageal atresia (EA). This epidemiological survey was recommended as part of a national rare diseases plan. METHODS All 38 national centers treating EA participated by completing for each patient at first discharge a questionnaire validated by a national committee of experts. Data were centralized by the national reference center for esophageal anomalies. Quantitative and qualitative analyses were performed, with P-values of less than 0.05 considered statistically significant. Results of the 2008-2009 data collection are presented in this report. RESULTS Three hundred seven new living cases of EA were recorded between January 1, 2008, and December 31, 2009. The male/female sex ratio was 1.3, and the live-birth prevalence of EA was 1.8 per 10,000 births. Major characteristics were comparable to those reported in the literature. Survival was 95%, and no correlation with caseload was noted. CONCLUSIONS Epidemiologic surveys of congenital anomalies such as EA, which is a rare disease, provide valuable data for public health authorities and fulfill one important mission of reference centers. When compared with previous epidemiological data, this national population-based registry suggests that the incidence of EA remains stable.

Is complex gastroschisis predictable by prenatal ultrasound

Please cite this paper as: Kuleva M, Khen‐Dunlop N, Dumez Y, Ville Y, Salomon L. Is complex gastroschisis predictable by prenatal ultrasound? BJOG 2012;119:102–109.

Bacteriologic epidemiology and empirical treatment of pediatric complicated appendicitis

Preoperative samples in the context of complicated appendicitis (CA) are rarely collected, and there is no consensus regarding the optimal antibiotic therapy in children. To help optimize empirical preoperative treatment, we studied clinical and bacteriologic data from a prospective cohort of 93 children with CA in a French hospital. All the bacteria isolated from peritoneal fluids were identified, using phenotypic and/or molecular techniques. The most commonly recovered species were Escherichia coli (71%), Streptococcus group milleri (34%), anaerobes (20%), and Pseudomonas aeruginosa (19%). The association piperacillin-tazobactam is an accurate choice of empirical therapy as it is active against 97% of bacteria. A third-generation cephalosporin with metronidazole in association with an aminoglycoside is a good alternative. Although antibiotic use may be considered as an adjunct to surgical intervention of CA, the appropriate use of preoperative antibiotics is essential and must be constantly reevaluated according to the bacterial epidemiology.

Value of 18F–fluoro-l-dopa PET in the Preoperative Localization of Focal Lesions in Congenital Hyperinsulinism

PURPOSE To retrospectively compare fluorine 18 ((18)F) fluoro-L-dopa positron emission tomography (PET) and pancreatic venous sampling (PVS) in the preoperative differentiation of diffuse from focal congenital hyperinsulinism (CHI) and localization of focal lesions. MATERIALS AND METHODS This study was approved by the institutional ethical committee, and informed consent for the research study was obtained from the parents of all subjects. Fifty-one patients evaluated for focal CHI between January 1, 1995, and January 31, 2008, were included. Thirty five underwent PVS evaluation alone, and 16 underwent a PET evaluation alone. The sensitivity values of each technique for the diagnosis and localization of focal lesions were compared in regard to results of surgery and pathologic analyses. In each patient, perioperative treatment was reviewed, and the presence of postoperative hypoglycemia was assessed as evidence of incomplete resection. Comparisons of the sensitivity values and recurrence rates were performed by using the Fisher exact test in regard to the number of patients. Comparisons of median age, weight, or number of biopsies were performed with a two-tailed unpaired Mann-Whitney U test. A difference with P < .05 was considered significant. RESULTS For PVS and PET groups, there was no error in differentiating focal from diffuse forms. PVS was not completed in four of 35 patients. In 27 (87%) of 31 patients in whom PVS was completed and 13 (81%) of 16 patients in whom PET was completed, preoperative localization of the focal lesion was in accordance with the surgical findings (P = .7). Although not significant, the number of biopsies performed before discovering the focal lesion was higher in the PET group compared with the PVS group (P = .06). Inadequate localization occurred in two (6%) patients in the PVS group and five (31%) patients in the PET group at initial preoperative imaging study; these patients underwent repeat surgery for residual CHI (P = .03). CONCLUSION (18)F-fluoro-L-dopa PET is equivalent to PVS in the characterization of CHI but does not provide localization of the lesion as precisely as does PVS.

Congenital diaphragmatic hernia: does gestational age at diagnosis matter when evaluating morbidity and mortality?

OBJECTIVE The objective of the investigation was to study the relationship between gestational age at diagnosis and mortality and morbidity in fetuses with an isolated congenital diaphragmatic hernia. STUDY DESIGN Between January 2008 and November 2013, 377 live births with isolated congenital diaphragmatic hernia diagnosed antenatally at a known gestational age were recorded in the database of the French National Center for Rare Diseases. The primary outcome studied was mortality estimated at 28 days and at 6 months. The secondary outcome was morbidity evaluated by pulmonary arterial hypertension at 48 hours, oxygen therapy dependence at 28 days, oral disorders, enteral feeding, and prosthetic patch repair. Analyses were adjusted for the main factors of congenital diaphragmatic hernia severity (side of the hernia, thoracic herniation of the liver, gestational age at birth, lung-to-head ratio, and prenatal treatment by tracheal occlusion. RESULTS Mortality rates at 28 days decreased significantly (P < .001) when gestational age at diagnosis increased: 61.1%, 39.2%, and 10.4% for a diagnosis in the first, second, and third trimester, respectively. Adjusted odds ratios were 3.12 [95% confidence interval, 1.86-5.25] and 0.35 [95% confidence interval, 0.18-0.66] for a diagnosis in the first and third trimesters, respectively, compared with a diagnosis in the second trimester. Similarly, morbidity decreased significantly when gestational age at diagnosis increased, and the trend remained significant after adjustment for the main factors of congenital diaphragmatic hernia severity (P < .001). CONCLUSION Gestational age at diagnosis is an independent predictor of postnatal prognosis for children presenting an isolated congenital diaphragmatic hernia and should be taken into account when estimating postnatal morbidity and mortality.

Biochemical amniotic fluid pattern for prenatal diagnosis of esophageal atresia.

Prenatal diagnosis of esophageal atresia (EA) may improve the outcome of affected neonates by allowing optimization of both prenatal and postnatal care. Prenatal sonographic detection is based on polyhydramnios and/or nonvisualization of the fetal stomach bubble, two signs with a large number of etiologies. We evaluated a biochemical approach to improving diagnostic efficiency. We compared amniotic fluid biochemical markers in 44 EA cases with 88 polyhydramnios and 88 nonpolyhydramnios controls. Both matched for GA with cases. Total proteins, alpha-fetoprotein (AFP), and digestive enzyme activities were assayed, including gamma-glutamyl transpeptidase (GGTP). We defined an EA index (AFP multiplied by GGTP). A significant difference (p < 0.0001) was observed for total protein, AFP, GGTP, and EA index between the EA group and each of the two control groups. No statistical difference was observed for any marker between the two most frequent EA subgroups (type I and type III) or between the two control groups. Using a cutoff of 3 for the EA index, 98% sensitivity and 100% specificity were observed for amniotic fluid prenatal diagnosis of EA, whatever the anatomical type. A large prospective series is required to confirm these results.

Does prenatal diagnosis modify neonatal treatment and early outcome of children with esophageal atresia

OBJECTIVE Our study aimed at (1) evaluating neonatal treatment and outcome of neonates with either a prenatal or a postnatal diagnosis of esophageal atresia (EA) and (2) analyzing the impact of prenatal diagnosis on outcome based on the type of EA. STUDY DESIGN We conducted a population-based study using data from the French National Register for infants with EA born from 2008-2010. We compared prenatal, maternal, and neonatal characteristics among children with prenatal vs postnatal diagnosis and EA types I and III. We defined a composite variable of morbidity (anastomotic esophageal leaks, recurrent fistula, stenosis) and death at 1 year. RESULTS Four hundred sixty-nine live births with EA were recorded with a prenatal diagnosis rate of 24.3%; 82.2% of EA type I were diagnosed prenatally compared with 17.9% of EA type III (P < .001). Transfer after birth was lower in case of prenatal diagnosis (25.6% vs 82.5%; P < .001). The delay between birth and first intervention did not differ significantly among groups. The defect size was longer among the prenatal diagnosis group (2.61 vs 1.48 cm; P < .001). The composite variables were higher in prenatal diagnosis subset (44% vs 27.6%; P = .003) and in EA type I than in type III (58.1% vs 28.3%; P < .001). CONCLUSION Despite the excellent survival rate of EA, cases with antenatal detection have a higher morbidity rate related to the EA type (type I and/or long gap). Even though it does not modify neonatal treatment and the 1-year outcome, prenatal diagnosis allows antenatal parental counselling and avoids postnatal transfers.

Specific biochemical amniotic fluid pattern of fetal isolated esophageal atresia.

Background:Perinatal care of esophageal atresia (EA) may be improved by prenatal diagnosis. Ultrasound findings (polyhydramnios and/or nonvisualization of fetal stomach) lead to a detection rate of ~50%. An amniotic fluid (AF) biochemical pattern characterized by high total protein, γ-glutamyl transpeptidase (GGTP), and normal l-leucine-aminopeptidase (AMP) leads to a 100% detection rate. The aim of this study was to explain this specific pattern.Methods:On the basis of enzyme activities assay, the following four objectives were sought: (i) comparing AF markers between EA and other digestive tract atresias, (ii) determining local GGTP synthesis in the esophagus (immunohistobiochemistry), (iii) determining the presence of a specific AF-AMP activity inhibitor, and (iv) comparing AF-AMP and AF-GGTP half-lives.Results:The AF-EA pattern was similar to that observed in upper duodenal atresia (above the Oddi sphincter). No local synthesis of GGTP was observed in the esophagus. No AF-AMP activity inhibitor was found. AF-GGTP had a longer half-life than AF-AMP.Conclusion:Due to the swallowing anomaly observed in EA, GGTP and AMP values physiologically observed at 18 wk will decrease on the basis of the half-lives of markers, with a flat slope for GGTP and a sharp slope for AMP, therefore explaining the differences observed in the AF-EA pattern.

Prenatal Intestinal Obstruction Affects the Myenteric Plexus and Causes Functional Bowel Impairment in Fetal Rat Experimental Model of Intestinal Atresia

Background Intestinal atresia is a rare congenital disorder with an incidence of 3/10 000 birth. About one-third of patients have severe intestinal dysfunction after surgical repair. We examined whether prenatal gastrointestinal obstruction might effect on the myenteric plexus and account for subsequent functional disorders. Methodology/Principal Findings We studied a rat model of surgically induced antenatal atresia, comparing intestinal samples from both sides of the obstruction and with healthy rat pups controls. Whole-mount preparations of the myenteric plexus were stained for choline acetyltransferase (ChAT) and nitric oxide synthase (nNOS). Quantitative reverse transcription PCR was used to analyze mRNAs for inflammatory markers. Functional motility and permeability analyses were performed in vitro. Phenotypic studies were also performed in 8 newborns with intestinal atresia. In the experimental model, the proportion of nNOS-immunoreactive neurons was similar in proximal and distal segments (6.7±4.6% vs 5.6±4.2%, p = 0.25), but proximal segments contained a higher proportion of ChAT-immunoreactive neurons (13.2±6.2% vs 7.5±4.3%, p = 0.005). Phenotypic changes were associated with a 100-fold lower concentration-dependent contractile response to carbachol and a 1.6-fold higher EFS-induced contractile response in proximal compared to distal segments. Transcellular (p = 0.002) but not paracellular permeability was increased. Comparison with controls showed that modifications involved not only proximal but also distal segments. Phenotypic studies in human atresia confirmed the changes in ChAT expression. Conclusion Experimental atresia in fetal rat induces differential myenteric plexus phenotypical as well as functional changes (motility and permeability) between the two sides of the obstruction. Delineating these changes might help to identify markers predictive of motility dysfunction and to define guidelines for post-surgical care.

Respiratory Morbidity in Infants Born With a Congenital Lung Malformation

In a multicenter cohort of children with congenital lung malformation, this study evaluates the frequency of respiratory symptoms and factors associated to their occurrence. BACKGROUND AND OBJECTIVES: The actual frequency of respiratory symptoms related to congenital pulmonary malformations (CPMs) remains undetermined. The goal of this study was to prospectively evaluate the respiratory symptoms occurring in infants with prenatally diagnosed CPMs, identify factors associated with the occurrence of these symptoms, and evaluate their resolution after surgery. METHODS: Infectious and noninfectious respiratory symptoms were prospectively collected in a French multicenter cohort of children with CPMs. RESULTS: Eighty-five children were followed up to the mean age of 2.1 ± 0.4 years. Six children (7%) underwent surgery during the first 28 days of life. Of the 79 remaining children, 33 (42%) had respiratory symptoms during infancy before any surgery. Wheezing was the dominant symptom (24 of 79 [30%]), and only 1 infant had documented infection of the cystic lobe. Symptoms were more frequent in children with noncystic CPMs, prenatally (P = .01) or postnatally (P < .03), and with postnatally hyperlucent CPMs (P < .01). Sixty-six children underwent surgery during the follow-up period, and 40% of them displayed symptoms after the intervention. Six children had documented pneumonia during the postoperative period. At the end of the follow-up, pectus excavatum was observed in 10 children, significantly associated with thoracotomy (P < .02) or with surgery before the age of 6 months (P < .002). CONCLUSIONS: CPMs are frequently associated with wheezing episodes. Surgery had no significant impact on these symptoms but was associated with a paradoxical increase in pulmonary infections, as well as an increased risk of pectus excavatum after thoracotomy.