Additional Major Anomalies Research Articles

Genetic diagnoses and associated anomalies in fetuses prenatally diagnosed with esophageal atresia.

Esophageal atresia (EA) is a congenital anomaly occurring in 2.3 per 10,000 live births. Due to advances in prenatal imaging, EA is more readily diagnosed, but data on the associated genetic diagnoses, other anomalies, and postnatal outcome for fetuses diagnosed prenatally with EA are scarce. We collected data from two academic medical centers (n = 61). Our data included fetuses with suspected EA on prenatal imaging that was confirmed postnatally and had at least one genetic test. In our cohort of 61 cases, 29 (49%) were born prematurely and 19% of those born alive died in the first 9 years of life. The most commonly associated birth defects were cardiac anomalies (67%) and spine anomalies (50%). A diagnosis was made in 61% of the cases; the most common diagnoses were vertebral defects, anal atresia, cardiac anomalies, tracheoesophageal fistula with esophageal atresia, radial or renal dysplasia, and limb anomalies association (43%, although 12% met only 2 of the criteria), trisomy 21 (5%), and CHARGE syndrome (5%). Our findings suggest that most fetuses with prenatally diagnosed EA have one or more additional major anomaly that warrants a more comprehensive clinical genetics evaluation. Fetuses diagnosed prenatally appear to represent a cohort with a worse outcome.

Long-term survival for infants born with orofacial clefts in Western Australia.

Only two population-based studies have reported survival beyond 15 years for individuals with orofacial clefts (OFC), and only for individuals with isolated OFC. Compared with the general population, long-term survival was similar for individuals with cleft lip only, and lower for individuals with cleft palate only. Results for those born with isolated cleft lip and cleft palate were inconsistent. Using linked population-based health data, including a congenital anomaly register with active surveillance and diagnoses up to 6 years, we compared survival at 1, 5, and 20 years for infants born 1980 to 2010 with, and without OFC. Of the 8112 live born infants in the cohort, 186 died before 20 years; most (81%) died during infancy. Compared with infants without OFC, infants born with all types of isolated OFC ± additional minor anomalies had similar infant survival (around 99%), but we found lower survival for infants with all cleft types and an additional major anomaly (66-84%). From 1 to 5 years, only infants with cleft palate only and an additional major anomaly had lower survival (97%) compared with children without OFC (99.9%). From 5 to 20 years, children with all cleft types, with or without additional major anomalies had similar survival to children without OFC (98-100%). Parents with a child diagnosed with an OFC ± additional minor anomalies only can be reassured that the OFC does not influence survival rates in infancy, or long-term. Infant survival was lower only for children with OFC and additional major anomalies.

Need for Fetal Autopsy and Genetic Diagnosis in Fetal Limb Anomalies

AbstractImproved antenatal imaging has led to increased detection rates of fetal limb anomalies. While they are nonlethal, they could be the first indication of an underlying genetic disorder. In the event of termination, postmortem and genetic evaluation are rarely performed, missing the opportunity to diagnose genetic disorders. The aim of the present study was to examine the utility of fetal autopsy in antenatally detected limb anomalies and to determine the incidence of genetic disorders in the same cohort. This was a retrospective evaluation of 59 cases. Only fetuses terminated for limb anomalies, either in isolation or in association with other features, were included. Cases terminated for lethal skeletal dysplasia and arthrogryposis multiplex congenita were excluded. Cases where limb defects were diagnosed after termination were also not included. The antenatal ultrasound records were compared to postmortem findings to determine the concordance rates. Chromosomal studies along with fetal autopsy were performed in all cases. Mutation analysis was also carried out where possible. Complete concordance between antenatal and postnatal findings was observed in 61 % of the cases. In 23.7 % of the cases, additional major anomalies were observed, the commonest being orofacial clefts. A genetic association was present in 62.7 % of the cases, of which, 25.4 % had an abnormal karyotype. Bilateral limb involvement and presence of associated features were strong predictors of genetic syndromes.

Predicting fetal karyotype in fetuses with omphalocele: The current role of ultrasound.

To assess the ability of ultrasound in predicting abnormal karyotype in pregnancies with prenatally diagnosed omphaloceles and to compare its test characteristics to previously published studies. A retrospective case-control study of omphaloceles diagnosed at one center was performed from 1995-2007. Cases were those with an abnormal karyotype and controls were those with a normal karyotype. Data collection included demographics, karyotype results, and ultrasound findings. The number and type of associated anomalies were compared between the cases and controls. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting an abnormal karyotype were calculated from previously published studies. Of the 73 subjects, there were 12 cases and 61 controls. The majority of women were Caucasian and primigravida. The cases were less likely to have an isolated omphalocele [1 (8.3%) vs. 27 (42.6%), OR = 0.122; 95% CI: 0.02-0.08] but were more likely to have two or more major anomalies [8 (66.7%) vs. 17 (27.9%), OR = 5.18; 95% CI: 1.19-24.04)] compared to the controls. Cardiac anomalies and only one additional major anomaly were not different between the two groups, P > 0.05. The test characteristics for this study were similar to previously published studies. Isolated omphaloceles were more likely to have a normal karyotype; however fetuses with multiple anomalies were more likely to have an abnormal karyotype. Despite advances in ultrasound technology, its ability for predicting an abnormal karyotype in these fetuses has not improved.

PF.66 Prognostic Significance an Enlarged Fetal Stomach in the Second Trimester

IntroductionDuodenal atresia classically presents with a “double bubble” sign and polyhydramnios in the third trimester. The significance of an enlarged stomach detected on a second trimester scan is unclear.MethodsA retrospective...

Prospective long-term follow up of children with anorectal malformation: Growth and development until 5 years of age

Background/purposeTo evaluate growth and development in children with anorectal malformations and to analyze effects of type of malformation and comorbidities. MethodsNon-syndromal children with anorectal malformations were prospectively evaluated at 0.5, 1, 2, and 5years. Biometrics were obtained at all visits. Mental and psychomotor function development was determined. Results108 children (59% male) were included. 49% had a high malformation, and 46% had ≥1 additional major comorbidity. All growth parameters were below the norm at all ages (p<0.01), irrespective of type of malformation. Children with ≥1 additional major anomaly had lower height at all ages; at 5years, mean (95% CI) height was −1.83 (−2.7 to −1.1) and −0.70 (−1.3 to −0.1) in children with and without comorbidities, respectively (p=0.019). Mental development was normal, irrespective of the type of malformation or comorbidities. Motor development was delayed at all ages. At 5years, motor development (n=30) was normal in 70%, borderline in 23%, and 7% had definitive motor problems (p=0.043). ConclusionNon-syndromal children with anorectal malformations are at risk for growth impairment, especially those with additional major comorbidity. Mental development is normal. Motor development is slightly impaired. Supportive care should focus on growth, dietary management, and motor development besides defecation problems.

Maternal caffeine consumption and risk of congenital limb deficiencies

Animal studies have shown that high doses of caffeine might cause congenital limb deficiencies (LDs); however, no epidemiologic studies have explored this relation. This case-control study assessed associations between maternal dietary caffeine and congenital LDs using data from the National Birth Defects Prevention Study (NBDPS), with 844 LD cases and 8069 controls from 1997 to 2007. Caffeine intakes from beverages (coffee, tea, and soda) and chocolate combined and by beverage type were examined. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated for subtypes of isolated LDs (no additional major anomalies) and LDs with other major anomalies separately, comparing the odds of 10 to <100, 100 to <200, 200 to <300, and 300+ mg/day total caffeine intake to 0 to <10 mg/day. All total dietary caffeine intake categories of 10 mg/day and above were marginally associated with odds of all isolated LDs combined (aOR, 1.4-1.7), isolated longitudinal LDs (aOR, 1.2-1.6), and isolated transverse LDs (aOR, 1.3-1.8) compared to the lowest intake category. A dose-response pattern for total dietary caffeine intake was not observed. A weak increased risk of congenital LDs associated with maternal dietary caffeine consumption was observed in this study; however, risk did not vary by amount of caffeine consumed.

Outcome of fetuses with a prenatal ultrasound diagnosis of isolated omphalocele

To assess the outcome following an ultrasound diagnosis of isolated fetal omphalocele (normal karyotype). Ultrasound database (1988-2002) was searched for omphalocele. Categories assigned as (1) isolated-no additional structural/karyotype anomalies, (2) associated minor abnormality, and (3) major structural/karyotype abnormalities. Ultrasound identified 65 cases, 13 with isolated omphalocele and 6 with associated minor anomalies. These 19 cases represented 29.2% of the population (19/65); isolated omphalocele was confirmed in 14 neonates (14/19, 73.7%). In five neonates, unrecognized by prenatal ultrasound were cardiac anomalies (2 cases), tracheoesophageal atresia with cardiac anomaly (1 case), and Beckwith-Wiedemann syndrome (BWS) (2 cases). A minor ultrasound finding did not predict further anomalies at birth. Preterm delivery complicated 37.5%; the only deaths occurred among preterm infants. Follow-up of isolated omphalocele found no long-term medical issues or learning disabilities except speech delay. Isolated fetal omphalocele is the exception. An additional minor ultrasound finding does not impact a relatively good prognosis with little long-term morbidity. However, this series highlights two areas of caution: (1) one-third were delivered preterm with a 50% rate of demise and (2) in a quarter of cases, an additional major anomaly or BWS was identified in the neonate.

OP01.17: Cerebral ventriculomegaly: is the prevalence increased for fetuses with trisomy 21?

Objective: To evaluate the correlation of trisomy 21 with ventriculomegaly diagnosed between 15 and 25 weeks. Methods: This study included 140 fetuses with cytogenetic diagnosis of trisomy 21 and detailed mid-trimester ultrasound examination in our prenatal center. This was a retrospective review of cases diagnosed between 1999 and 2006. Prenatal or postnatal karyotyping, ultrasound video and DVD recordings, still frames and ultrasound reports were analyzed in all included cases. Results: Six cases (4.3%) of mild ventriculomegaly (10–12 mm) were detected among 140 fetuses with Down’s syndrome. Five of these fetuses had additional soft marker: mild nuchal edema (3 cases), short nasal bone (4 cases), short femur and humerus (2 cases), echogenic intracardiac focus (2 cases). In three fetuses additional major anomalies were diagnosed: one case with VSD, one case with AVSD, one case with nonimmune hydrops. Only one fetus had isolated ventriculomegaly and no other signs of trisomy 21. No case of severe degree of ventriculomegaly (> 12 mm ventricular atrial diameter) was found in our collective of trisomy 21 fetuses. Conclusions: Since 4.3% of the fetuses with trisomy 21 were affected by mild ventriculomegaly the risk for trisomy 21 is increased above average when sonographic examination reveals this marker. We diagnosed 151 cases of mild ventriculomegaly in 43.490 US examinations in our center, the prevalence for all fetuses was 0.35%. However ventriculomegaly as isolated observation is rarely found. Associated anomalies involving other organs are common in cases with trisomy 21. Nevertheless we conclude that karyotyping is recommended in all cases with ventriculomegaly.

Outcomes of Congenital Diaphragmatic Hernia: A Population-Based Study in Western Australia

Outcomes of Congenital Diaphragmatic Hernia: A Population-Based Study in Western Australia

Duplicate exstrophy of the bladder

Duplicate exstrophy of the bladder is a rare, distinct congenital anomaly without additional major anomalies of the urinary tract. A 15-year-old boy with duplicate exstrophy is reported on, and the possible role of bladder sequestration in the development of classical musculoskeletal deformities in this anomaly is discussed.

Critical aortic coarctation: Patch aortoplasty in infants less than age 3 months

Twenty-three infants less than age 3 months (mean age 31 days) underwent patch aortoplasty for relief of coarctation of the aorta. All had intractable congestive heart failure, despite aggressive medical therapy. Each infant had other cardiac anomalies, including patent ductus arteriosus (83 percent) and ventricular septal defect (74 percent). All patients underwent closure of the ductus arteriosus and patch angioplasty of the aorta to produce a luminal diameter of at least 16 mm. In addition, 9 of the 17 patients (53 percent) with a large shunt ventricular septal defect underwent pulmonary arterial banding. There was one hospital death 42 days after operation secondary to bowel perforation and sepsis. Hospitalization beyond 21 days postoperatively was always due to other unrepaired cardiac lesions. The three late deaths at 3, 9 and 18 months after operation were associated with additional major anomalies. Fourteen patients have had postoperative catheterization. No gradient was found across the site of coarctation repair, but one patient had a gradient between the left carotid and left subclavian arteries. Surgical repair of critical coarctation of the aorta in infants can safely be offered despite the presence of other cardiac anomalies.

Congenital fusion of the thalami (atresia of the third ventricle) and associated anomalies in a 6-months-old infant.

The case is reported of a 6 months old infant boy who had gradually increasing hydrocephalus since birth. Ventriculograms showed greatly dilated lateral ventricles and an apparent mass in the area of the third ventricle which failed to fill. Necropsy showed congenital atresia of the upper portion of the fourth ventricle, the entire aqueduct and the third ventricle. The two thalami were fused in the midline. No gliosis was present in the areas of ventricular and aqueductal occlusion. Microscopic clusters of ependymal cells, separated from each other by normal nervous tissue, indicated the region of obliterated ventricles and aqueduct. As further expressions of a tendency of nervous tissue fusion in the midline, the colliculi of the quadrigeminal plate were fused into one dorsal protuberance and the incisures separating the cerebellar hemispheres were absent. The dentate nuclei were also fused in the midline. An additional major anomaly was agenesis of the right lung. The etiology of these malformations is unknown at present, but the changes in the brain, brain stem and cerebellum appear to be an exaggeration of the normal “closing in” of midline structures, such as the physiological narrowing of the large fetal aqueduct and the normal unification of the two lateral cerebellar primordia. To our knowledge this is the first reported case of congenital atresia of the third ventricle and fusion of the cerebellar hemispheres and dentate nuclei. The fused thalami created the rontgenological impression of a neoplasm of the third ventricle.