Andreas Heydweiller

Prenatal Diagnosis and Evaluation of Sonographic Predictors for Intervention and Adverse Outcome in Congenital Pulmonary Airway Malformation

Objective To describe antenatal findings and evaluate prenatal risk parameters for adverse outcome or need for intervention in fetuses with congenital pulmonary airway malformation (CPAM). Methods In our retrospective study all fetuses with a prenatal diagnosis of CPAM detected in our tertiary referral center between 2002 and 2013 were analyzed. Sonographic findings were noted and measurements of mass-to-thorax-ratio (MTR), congenital pulmonary airway malformation volume-ratio (CVR) and observed to expected lung-to head-ratio (o/e LHR) were conducted and correlated to fetal or neonatal morbidity and mortality and/or need for prenatal intervention. Results 67 fetuses with CPAM were included in the study. Hydropic fetuses were observed in 16.4% (11/67) of cases, prenatal intervention was undertaken in 9 cases; 7 pregnancies were terminated. The survival rate of non-hydropic fetuses with conservatively managed CPAM was 98.0% (50/51), the survival rate for hydropic fetuses with intention to treat was 42.9% (3/7). 10 (18.2%) children needed respiratory assistance. Fetuses with a CVR of <0.91 were significantly less likely to experience adverse outcome or need for prenatal intervention with sensitivity, specificity and positive/negative predictive value of 0.89, 0.71, 0.62 and 0.93, respectively. A MTR (mass-to-thorax-ratio) of < 0.51 had a positive predictive value of 0.54 and a negative predictive value of 0.96 of adverse events with a sensitivity of 0.95 and a specificity of 0.63. The negative predictive value for o/e LHR of 45% was 0.84 with sensitivity, specificity and positive predictive value of 0.73, 0.68 and 0.52, respectively. Conclusions The majority of cases with CPAM have a favorable outcome. MTR and CVR are able to identify fetuses at risk, the o/e LHR is less sensitive.

Bronchopulmonary sequestration with massive pleural effusion: pleuroamniotic shunting vs intrafetal vascular laser ablation

To assess the incidence of complications among a relatively large cohort of fetuses with bronchopulmonary sequestration (BPS) and the success of two different intrauterine treatment modalities.

Nine new twin pairs with esophageal atresia: A review of the literature and performance of a twin study of the disorder

BACKGROUND Isolated esophageal atresia (EA) is a rare congenital malformation whose etiology remains largely unknown. Nine twin pairs with EA were identified from our clinical service, prompting the performance of a systematic review of the literature and the first reported twin study of isolated EA. METHODS A total of 330 twin pairs with EA were identified from the literature. The zygosity, concordance, and malformation (isolated vs. nonisolated) status of all 339 twin pairs were evaluated. A total of 72 twin pairs (4 of 9 / 68 of 330) fulfilled the criteria for inclusion in a classic twin study of isolated EA. RESULTS The pairwise concordance rates were 50% (95% confidence interval [CI], 34-66%) for monozygous (MZ) twin pairs and 26% (95% CI, 15-42%) for dizygous (DZ) twin pairs (p = 0.033). The probandwise concordance rates were 67% (95% CI, 53-78%) for MZ twin pairs and 42% (95% CI, 29-56%) for DZ twin pairs (p = 0.011). The MZ/DZ ratios were 1.9 for pairwise analysis and 1.6 for probandwise analysis. The familial risk ratios for MZ and DZ twin pairs were 1700 and 900, respectively. CONCLUSION The observation of higher concordance rates for MZ compared to DZ twin pairs indicates that genetic factors contribute to isolated EA.

Comparison of environmental risk factors for esophageal atresia, anorectal malformations, and the combined phenotype in 263 German families

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and anorectal malformations (ARM) represent the severe ends of the fore- and hindgut malformation spectra. Previous research suggests that environmental factors are implicated in their etiology. These risk factors might indicate the influence of specific etiological mechanisms on distinct developmental processes (e.g. fore- vs. hindgut malformation). The present study compared environmental factors in patients with isolated EA/TEF, isolated ARM, and the combined phenotype during the periconceptional period and the first trimester of pregnancy in order to investigate the hypothesis that fore- and hindgut malformations involve differing environmental factors. Patients with isolated EA/TEF (n = 98), isolated ARM (n = 123), and the combined phenotype (n = 42) were included. Families were recruited within the context of two German multicenter studies of the genetic and environmental causes of EA/TEF (great consortium) and ARM (CURE-Net). Exposures of interest were ascertained using an epidemiological questionnaire. Chi-square, Fishers exact, and Mann-Whitney U-tests were used to assess differences between the three phenotypes. Newborns with isolated EA/TEF and the combined phenotype had significantly lower birth weights than newborns with isolated ARM (P = 0.001 and P < 0.0001, respectively). Mothers of isolated EA/TEF consumed more alcohol periconceptional (80%) than mothers of isolated ARM or the combined phenotype (each 67%). Parental smoking (P = 0.003) and artificial reproductive techniques (P = 0.03) were associated with isolated ARM. Unexpectedly, maternal periconceptional multivitamin supplementation was most frequent among patients with the most severe form of disorder, i.e. the combined phenotype (19%). Significant differences in birth weight were apparent between the three phenotype groups. This might be attributable to the limited ability of EA/TEF fetuses to swallow amniotic fluid, thus depriving them of its nutritive properties. Furthermore, the present data suggest that fore- and hindgut malformations involve differing environmental factors. Maternal periconceptional multivitamin supplementation was highest among patients with the combined phenotype. This latter finding is contrary to expectation, and warrants further analysis in large prospective epidemiological studies.

Second study on the recurrence risk of isolated esophageal atresia with or without trachea‐esophageal fistula among first‐degree relatives: No evidence for increased risk of recurrence of EA/TEF or for malformations of the VATER/VACTERL association spectrum

BACKGROUND Esophageal atresia with/without trachea-esophageal fistula (EA/TEF) denotes a spectrum of severe congenital malformations. The aim of this systematic study was to determine both the recurrence risk for EA/TEF, and the risk for malformations of the VATER/VACTERL association spectrum, in first-degree relatives of patients with isolated EA/TEF. METHODS A total of 108 unrelated patients with isolated EA/TEF were included. These individuals had 410 first-degree relatives including 194 siblings. The presence of EA/TEF and malformations of the VATER/VACTERL association spectrum in relatives was systematically assessed. Data from the EUROCAT network were used for comparison. RESULTS None of the first-degree relatives displayed any form of EA/TEF. In two families, a first-degree relative presented with malformations from the VATER/VACTERL association spectrum. However, no increase in the risk for malformations of the VATER/VACTERL association spectrum was found compared with the control cohort (p = 0.87). In three families, one more distantly related relative presented with EA/TEF. CONCLUSION In contrast to previous studies, our results suggest a very low recurrence risk for isolated EA/TEF and/or for malformations of the VATER/VACTERL association spectrum among first-degree relatives.

Intestinal Atresia, Encephalocele, and Cardiac Malformations in Infants with 47,XXX: Expansion of the Phenotypic Spectrum and a Review of the Literature

Identification of the 47,XXX karyotype often occurs adventitiously during prenatal fetal karyotyping in cases of advanced maternal age. Although most females with 47,XXX appear healthy at birth, various types of congenital malformations have been reported, of which urinary tract anomalies are the most frequent. We report on 2 newborns with 47,XXX and congenital cardiac defects, one of whom had duodenal atresia and the other an occipital encephalocele. This expands the spectrum of malformations reported in association with the triple-X syndrome. We also present a review of the literature on non-urinary tract malformations in females with 47,XXX. We conclude that prenatal identification of the 47,XXX karyotype is an indication for detailed fetal ultrasonography which should include examination of multiple organ systems. Such prenatal screening for possible associated congenital malformations should help to ensure optimal perinatal clinical management of 47,XXX cases.

Esophageal Atresia with or without Tracheoesophageal Fistula (EA/TEF): Association of Different EA/TEF Subtypes with Specific Co-occurring Congenital Anomalies and Implications for Diagnostic Workup.

Background Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) represents the most common developmental malformation of the upper digestive tract. It is classified into six subtypes according to the classification of Vogt, depending on anatomical variation of this malformation. Around 50% of the patients with EA/TEF present additional anomalies, which often influence, next to the EA/TEF subtype, the overall prognosis of EA/TEF newborns. Here, we investigated the association of the different EA/TEF subtypes with co‐occurring congenital anomalies in EA/TEF patients and demonstrate their implications for postnatal diagnostic workup. Materials and Methods We investigated 333 patients of a large German multicenter study born between 1980 and 2012. After evaluation of all available clinical records, 235 patients were included in our analysis. We compared our results with existing data. Results The highest risk for co‐occurring anomalies was seen in patients with most common Vogt 3b (p = 0.024), especially for additional gastrointestinal anomalies (p = 0.04). Co‐occurring anomalies of the skin were significantly more common in patients with subtype Vogt 2 (p = 0.024). A significant correlation was observed for an impaired neurodevelopmental outcome and EA/TEF Vogt 3a (p = 0.041). Patients with EA/TEF showed a higher risk to present with any additional congenital anomaly compared with the general population (p < 0.001). Conclusion Our results warrant thorough clinical workup for gastrointestinal anomalies especially in patients with Vogt 3b. Moreover, it might be necessary to focus on a thorough aftercare for neurocognitive development in patients with Vogt 3a. The here presented observations need to be confirmed by future studies.

1403 Does Amnioticfluid Play a Nutritive Role Before Birth? a Retrospective Analysis of Newborninfants with Upper and Lower Gastrointestinal Atresia

Introduction During pregnancy the fetus swallows and absorbs an increasing amount of amnioticfluid. It remains unclear whether a lack of absorption of amniotic fluid may result in low birth weight (BW). There are a few studies evaluating the significance of amniotic fluid on fetal growth and the their results are controversial. This study was carried out to evaluate the intrauterine nutritive role of amniotic fluid on fetal growth. Method Neonates with atresia of gastrointestinal tract (GIT) during a period of 12 years were studied retrospectively. 29 from 100 patients were excluded from the statistical analysis because of VATER (VACTERL) association (8), chromosomal abnormalities (11) and congenital heart anomalies (10). BW and birth length (BL) from 71 infants (esophageal atresia (20), duodenal atresia (16), jejunal atresia (7), ileal atresia (11) and anal atresia (17) compared between infants with atresia of upper GIT (AUGIT; esophagus, duodenum) and atresia of lower GIT (ALGIT; jejunum, ileum, colon and anal atresia). Results There is a significant difference in BW between UGIA and LGIA: BW below the 10th percentile was observed in 16 of 36 patients (44%) with UGIA and only 6 of 35 patients (17%) with LGIA (p= 0.012, UGIA vs. LGIA). There is no statistical significant difference for BL between both groups (p=0.735). Conclusion Newborn infants with UGIA had lower birth weight than newborn infants with LGIA. This would be in agreement with the hypothesis that absence or decrease of absorption of amniotic fluid in the fetus leads to lower birth weight.

Temporary Banding of a Lower Tracheoesophageal Fistula in an Infant with Left Congenital Diaphragmatic Hernia and Esophageal Atresia

Congenital diaphragmatic hernia (CDH) and esophageal atresia (EA) are relatively common congenital malformations with an incidence of 1 per 2500–3000 live births [7,20,21]. The incidence of associated malformations in fetuses with both CDH and EA can be as high as 33–71% [7, 12,14,21]. CDH associated with EA, with or without tracheoesophageal fistula (TEF), has been reported only in 25 cases and is considered highly lethal [1–6,8– 11,13,15–19,22–24]. We present here a preterm male newborn with a severe left CDH with EA and lower TEF and review the literature.