Objective. To present any congenital anomalies with respect to tumor necrosis factor (TNF) antagonists reported to the US Food and Drug Administration (FDA) to determine if there are common findings. Methods. A review of the FDA database of reported adverse events with etanercept, infliximab, and adalimumab from 1999 through December of 2005 was performed. Key words for congenital anomalies were employed as search tools. Duplicate reports were eliminated. Any concomitant medicines were recorded. Results. Our review of > 120,000 adverse events revealed a total of 61 congenital anomalies in 41 children born to mothers taking a TNF antagonist. Of these mothers, 22 took etanercept and 19 took infliximab. There were no reports in women taking adalimumab. The most common reported congenital anomaly was some form of heart defect. Twenty-four of the 41 (59%) children had one or more congenital anomalies that are part of vertebral abnormalities, anal atresia, cardiac defect, tracheoesophageal, renal, and limp abnormalities (VACTERL) association. There were 34 specific types of congenital anomalies in total, and 19 (56%) of those are part of the VACTERL spectrum. Nine of these 19 (47%) types of VACTERL anomalies were observed statistically significantly more than historical controls (p Conclusion. A seemingly high number of congenital anomalies that are part of the VACTERL spectrum have been reported. These congenital anomalies are occurring at a rate higher than historical controls. This commonality raises concerns of a possible causative effect of the TNF antagonists.

https://www.jrheum.org/content/jrheum/36/3/635.full.pdf

A Safety Assessment of Tumor Necrosis Factor Antagonists During Pregnancy : A Review of the Food and Drug Administration Database

Objective

To evaluate the contribution of new imaging techniques in the prenatal diagnosis of skeletal dysplasia.



Methods

Between May and October 2003, a prospective study was conducted in a single referral center. Three-dimensional ultrasound (3D-US) and three-dimensional helical computer tomography (3D-HCT) were performed after two-dimensional ultrasound (2D-US) in six cases of skeletal dysplasia. Diagnostic accuracy and detailed findings with each of the three techniques were compared with postnatal radiological findings.



Results

There were three cases of achondroplasia, two cases of osteogenesis imperfecta type II and one case of chondrodysplasia punctata. Termination of pregnancy was performed in five cases and one fetus with osteogenesis imperfecta type II was delivered at term by Cesarean section. 2D-US made the correct diagnosis in four cases. 3D-US and 3D-HCT achieved an accurate diagnosis in all six cases. 3D-HCT and 3D-US identified significantly more abnormalities than did 2D-US (3D-HCT: 94.3% (33/35); 3D-US: 77.1% (27/35); 2D-US: 51.4% (18/35); P < 0.01). The diagnosis was made between 27 and 36 weeks' gestation in all cases. The advantage of 3D-HCT over 3D-US was the possibility of imaging the entire fetus.



Conclusion

3D-US and 3D-HCT seem to be useful complementary methods to 2D-US, and may improve accuracy of the prenatal diagnosis of skeletal disorders. These new imaging technologies may have a role in the prenatal multidisciplinary approach to the diagnosis of skeletal dysplasias. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.

https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1002/uog.1113

Prenatal diagnosis of fetal skeletal dysplasias by combining two-dimensional and three-dimensional ultrasound and intrauterine three-dimensional helical computer tomography

Jeune syndrome, originally described as asphyxiating thoracic dystrophy by Jeune et al [Jeune et al (1955); Arch Fr Pediatr 12:886-891], is an autosomal recessive osteochondrodysplasia with characteristic skeletal abnormalities, and variable renal, hepatic, pancreatic, and retinal complications We present eight patients, including two brothers with Jeune syndrome, and an extensive review of 118 cases in the published literature with the purposes of: (1) defining the clinical and radiological diagnostic criteria for Jeune syndrome; (2) comparing our cases to those in the literature meeting the documented clinical and radiological findings of Jeune syndrome, in order to: (3) provide an accurate clinical characterization of Jeune syndrome with frequency of associated complications and outcome data In order to estimate the frequency of phenotypic abnormalities in Jeune syndrome as precisely as possible, we did not include reports in the literature with incomplete descriptions of the radiologic and clinical findings, nor those reports having additional findings overlapping with other syndromes We found that the occurrence of renal, hepatic, and ophthalmologic complications is variable; does not correlate with severity of the skeletal phenotype; nor is it predictable even with the presence of a well-defined skeletal phenotype, as in this study Based upon these cases with Jeune syndrome, renal and hepatic abnormalities occur in approximately 30% of cases, with renal failure occurring in 38% of those with kidney involvement Eye abnormalities are reported in 15%, but it is unclear whether this represents under-ascertainment There is a 12:1 ratio between living and deceased patients; a respiratory cause of death is most common, occurring almost exclusively in those less than 2 years of age, and a renal etiology accounts for all deaths between the ages of 3-10 years of age There is a paucity of affected individuals reported in the literature greater than age 20 years, and a lack of longitudinal data to obtain accurate data on morbidity and mortality of Jeune syndrome at older ages This study provides a well-defined group of patients with Jeune syndrome with delineation of the frequency of associated findings, which may form a basis for current and future genotype-phenotype studies

Clinical Insights Gained From Eight New Cases and Review of Reported Cases With Jeune Syndrome (Asphyxiating Thoracic Dystrophy)

Congenital Tracheal Anomalies

Objective To examine the indications, risks, and surgical outcomes after tracheal reconstruction using cadaveric homograft in children. Design Retrospective medical record review. Setting Tertiary referral center. Patients Ten children (4 boys and 6 girls). Intervention Tracheal reconstruction using cadaveric homograft. Main Outcome Measures Cause of stenosis, number and type of procedures before homograft reconstruction, severity of preoperative stenosis, surgical approach, homograft length, duration of stenting, number and type of procedures after reconstruction, and rates of decannulation and survival. Results Ten children (mean [SD] age, 8.4 [5.5] years) underwent 14 tracheal reconstructions using cadaveric homograft. Patients had an average of 7.0 (range, 1-16) procedures before homograft reconstruction, including an average of 2.8 (range, 0-6) major open airway reconstructions. Mean (SD) pretracheoplasty Myer-Cotton grade of stenosis was 3.80 (0.42) (range, 3-4), and all patients were tracheotomy dependent. A cervical approach was used in 12 reconstructions (86%), and 2 (14%) required median sternotomy. Mean (SD) homograft length was 3.9 (1.7) cm (range, 2-8 cm), which was approximately 0.60 times the length of the total recipient trachea. Mean (SD) duration of stenting for all homografts was 0.67 (0.46) years (range, 0.24-1.98 years). The survival rate was 90% after a mean follow-up of 5.47 (1.52) years (range, 3.32-7.55 years). Surviving patients required an average of 7.38 (5.52) procedures (range, 1-19) after homograft transplant, including an average of 1 major open airway reconstruction (range, 0-4). The mean (SD) grade of stenosis after the final homograft placement was 1.89 (1.27) (range, 1-4). Although the operation-specific decannulation rate was only 7% (1 of 14), the overall decannulation rate eventually reached 60%. Statistical bootstrapping methods and a multivariate regression model determined that increasing patient age (odds ratio, 1.21; 95% confidence interval, 1.07-1.36), increasing number of prior procedures (1.26; 1.02-1.57), and increasing homograft length (2.42; 1.60-3.40 [P  Conclusions Tracheal reconstruction using cadaveric homograft is an option in children who have undergone multiple airway surgical procedures and present with long-segment stenoses that cannot be bridged using conventional methods. These patients must receive close postoperative follow-up. Subsequent procedures are almost always required before decannulation, and eventual decannulation rates are only 60%. Decannulation rates are lower in older patients who have previously undergone many procedures and require a long tracheal homograft.

https://jamanetwork.com/journals/jamaotolaryngology/articlepdf/716333/ooa15025_583_590.pdf

Pediatric tracheal reconstruction using cadaveric homograft.

Isolated type III tracheal agenesis without associated congenital anomalies is very rare. Therefore, infants with this type of isolated defects are potential candidates for surgical correction. We present three cases of tracheal agenesis (Floyd's type III) with no other major abnormalities and reviewed the literature. We also discussed the previously attempted surgical procedures with the hope that in future, with advances in surgical reconstruction, there may be a better solution for this lethal anomaly.

Tracheal agenesis: Report of three cases and review of the literature

We describe prenatal sonographic findings in a 34-week fetus with Jeune syndrome or asphyxiating thoracic dystrophy (ATD). The long bones measured were less than third percentile; the thoracic circumference (TC) measured 216 mm (< 2.5th percentile); the abdominal circumference (AC) measured 303.5 mm (50th – 75th percentiles) and the rib cage perimeter (RCP) measured was 98 mm. The TC/AC was 0.70 (normal, 0.85) and the RCP/TC was 0.45 (normal, 0.68). Following birth diagnosis of Jeune syndrome was made based on radiographic analysis, which was subsequently confirmed by clinical and postmortem examination. This case highlights the utility of both TC/AC and RCP/TC in diagnosis of ATD and other skeletal dysplasias associated with a small thorax.

Fetal thoracic measurements in prenatal diagnosis of jeune syndrome

Congenital syphilis (CS) continues to occur despite widespread serologic testing of pregnant women.' The incidence of CS generally reflects the prevalence of untreated primary and secondary syphilis in women of childbearing age? Reported cases of CS in the United States increased from 115 to 268 during the period 1978-1985: Metropolitan New York and three states-Texas, California, and Florida-accounted for 80% of the reported cases of CS in 1985. Mascola et al., after a retrospective review of 50 cases under 1 year of age, identified risk factors for developing CS.' A prospective study was undertaken in a section of New York City to determine factors that may have resulted in failure of prevention of CS in the first week of life.

Anasuya Nagaraj

Papers

Tracheal agenesis: Report of three cases and review of the literature

Fetal thoracic measurements in prenatal diagnosis of jeune syndrome

Congenital Syphilis in an Urban Population