Francine Tessier

Outcome of fetuses diagnosed with atrioventricular septal defect

OBJECTIVE To quantify the association of prenatally diagnosed atrioventricular septal defect with Down syndrome and to evaluate its impact on obstetric and neonatal outcomes. METHODS Charts of 42 cases of atrioventricular septal defect diagnosed by fetal echocardiography from July 1985 to July 1997 were reviewed for prenatal history and outcome data (pregnancy outcome, pathologic confirmation, postnatal echocardiographic findings, and neonatal outcome). Statistical analysis was done using Fisher exact test and odds ratios. RESULTS The mean gestational age at diagnosis was 26 weeks. Four cases could not be confirmed antenatally on repeat echocardiograms and were excluded. Reasons for referral of the remaining 38 fetuses included an abnormal four-chamber view in 76%. Twenty-two fetuses (58%) had abnormal karyotypes: 19 trisomy 21, one trisomy 18, one trisomy 13, and one mosaicism. The cardiac lesions were isolated in 20 fetuses (53%). After excluding cases of termination, ten of 12 fetuses (83%) with Down syndrome survived, compared with seven of 13 (54%) with normal karyotypes (P = .125). The odds of trisomy 21 were 16 times higher (95% confidence interval 3.0, 85.3) in fetuses with isolated cardiac lesions compared with those with associated cardiac anomalies. CONCLUSION Prenatal diagnosis of atrioventricular septal defect was associated with a 58% risk of aneuploidy (mainly trisomy 21). Down syndrome fetuses with this cardiac anomaly appeared to have a better survival rate than fetuses with normal karyotypes. Our sample did not have enough power to show a statistically significant difference. When an isolated atrioventricular septal defect was diagnosed prenatally, the odds of trisomy 21 were significantly higher than when other associated cardiac lesions were diagnosed. This information should be considered in prenatal counseling for atrioventricular septal defect.

Prediction of pediatric outcome after prenatal diagnosis and expectant antenatal management of congenital cystic adenomatoid malformation.

Objective: To determine whether the congenital cystic adenomatoid malformation (CCAM) volume ratio (CVR) is associated with fetal and postnatal outcome after prenatal diagnosis and antenatal expectant management in a provincial tertiary referral center that does not offer fetal surgery. Methods: Retrospective cohort of 71 consecutive cases of prenatally diagnosed CCAM meeting study criteria (1996–2004). CVR was calculated on the initial ultrasound at the referral center, and associated with hydrops (Fisher’s exact test) and a composite adverse postnatal outcome consisting of death, intubation for respiratory distress, extracorporeal membrane oxygenation, non-elective surgery for symptomatology, or respiratory infection requiring hospital admission (Mann-Whitney test). Results: A CVR >1.6 was significantly associated with hydrops (p = 0.003). In addition, the CVR was significantly associated with the composite adverse postnatal outcome (p = 0.004) at a mean age of follow-up of 41 months (range <1–117 months). For CVR and postnatal outcome, the area-under-the-curve receiver operating characteristic was 0.81 (95% CI 0.69–0.93, p = 0.006), and choosing a CVR cut-off of <0.56, the negative predictive value was 100% (95% CI 0.85–1.00). Conclusion: In a provincial referral center with antenatal expectant management of CCAM, the CVR was associated with hydrops and postnatal outcome, with a CVR <0.56 predictive of good prognosis after birth.

Beckwith–Wiedemann syndrome in sibs discordant for IC2 methylation†‡

Genetically heterogeneous imprinting disorders include Beckwith–Wiedemann syndrome (BWS) and multiple maternal hypomethylation syndrome (MMHS). Using DNA sequencing, quantitative PCR, SNuPE, pyrosequencing, and hybridization to the Illumina GoldenGate Methylation Cancer Panel 1 array, we characterized the genomic DNA of two brothers with BWS who were discordant for loss of methylation at several differentially methylated regions (DMR), including imprinting center 2 (IC2) on chromosome band 11p15.5, which is often hypomethylated in BWS. In keeping with MMHS, the elder child had hypomethylation of SGCE and PLAGL1 as well as of IC2, whereas the younger brother demonstrated no loss of methylation at these DMRs. Although this discordance is consistent with the observation that 15–20% of individuals with BWS do not have detectable genetic or epigenetic alterations of 11p15.5, this is the first report of familial recurrence of BWS with discordance for chromosomal 11p15.5 alterations. We hypothesize that this apparent discordance arises either from mosaicism precluding identification of IC2 hypomethylation in blood or buccal mucosa DNA of the younger child, or from hypomethylation at a site not interrogated by our molecular studies.

Is the Nuchal Index Increased in Fetuses with Congenital Structural Heart Defects

Objectives: To determine if the Nuchal index (NIx) is increased in euploid fetuses with structural congenital heart defects (CHD). Methods: Euploid fetuses with CHD between 18 and 24 weeks gestation were identified. The next fetus meeting the same criteria with a normal fetal echocardiogram were selected as a control. The NIx [(mean nuchal thickness /mean biparietal diameter) × 100] and cardiac axis (CA; degrees) were calculated for each fetus. Standard descriptive tests and two-tailed t test were used. Results: The NIx in the abnormal (n = 20) and control (n = 20) groups were 9.10 (2.35) and 7.54 (p = 0.04) and CA was 55.8° and 48.6° (p = 0.02), respectively. Conclusions: The NIx and CA were significantly different in fetuses with CHD. A prospective study to confirm these findings and determine clinical utility is warranted.

P05.01: Is the nuchal index increased in fetuses with congenital structural heart defects? A prospective study

Objectives: To determine if the Nuchal Index (NIx) is increased in euploid fetuses diagnosed with an isolated structural congenital heart defect (CHD) on fetal echocardiogram. Methods: A prospective case-control study was conducted from March 2002 to July 2003. All patients between 18 and 24 weeks’ gestation referred for fetal echocardiography were approached for participation. Patients were excluded if other major anomalies or an abnormal karyotype were present. The NIx was calculated as the mean nuchal thickness/mean biparietal diameter ×100. Fetal cardiac axis was calculated from hard copy images in a blinded fashion. Analysis was by standard descriptive tests, 2-tailed t-test, receiver operating characteristic (ROC) curve, univariate analysis and discriminant analysis. Cases were classified as normal or abnormal as per the co-authors diagnosis at the time of the fetal echocardiogram. Results: Of the 607 echocardiograms performed, 314 were eligible. Two hundred and seven (22 abnormals and 185 normals) were recruited for a capture rate of 65.9%. The mean NIx in the abnormal and normal group was 9.3 and 7.8 respectively. This was statistically significant (p = 0.003). Using a cut-off of 10.4 at a 5% false positive rate, the sensitivity was 29% with an ROC of 0.699 [95%CI 0.582, 0.816]. Eleven of the 22 abnormal hearts and 7/185 normals had an abnormal cardiac axis. (OR 0.04 [95%CI 0.01, 0.12, p < 0.00001]). Although NIx and Nth were different between the study groups, discriminant analysis was unable to identify an adequate cut-off to allow adequate prediction of CHD. Conclusions: The NIx and CA were significantly different in fetuses with CHD in a high-risk population. However, an appropriate cutoff value could not be found in our study. Further studies in a low-risk population are warranted.

P05.26: Cardiac rhabdomyoma in the left ventricular outflow tract of a fetus

Gest. age at diagnosis 18 weeks 21 weeks 20 weeks 22 weeks, maternal Associated findings Poor cardiac function, small nuchal cystic hygroma, echogenic bowel, club foot Fetal hydrops, large placenta Bilateral hydronephrosis, placental abruption Ascites, cerebral ventriculomegaly, decreased cardiac function. On f/u: resolution of ascites, progressive ventriculomegaly with microcephaly and mural calcifications, persistent patchy echogenic myocardium. Fetal echocardiography Epicardial calcifications, poor bi-ventricular function, possible hypoplastic RV, bouts of SVT Heart enlarged, diffusely echogenic, poor contractility, bradycardia 80–90 bpm N/A Normal anatomy, generalized brightness of myocardium, moderately decreased function which improved on followup Karyotype 46,XY 46,XX N/A 46,XY Outcome TOP TOP IUFD C/S at 37 weeks, 2790 gr Histo-pathology/postnatal followup Structurally normal heart, near-circumferential calcification of epicardium and transmural involvement of RV outflow tract. Small bowel calcification. Structurally normal heart, extensive atrial and focal epicardial scarring with calcification. Structurally normal heart, calcified epicardial collagen, fibrosis and calcification of myometrium deep to epicardial calcifications, focal papillary muscle calcification. Large clot adherent to placenta, rt. upper quadrant calcifications. Seizures, hydrocephalus with shunt placement, microcephaly, chorioretinal abnormalities, sensorineural deafness, cognitive developmental delay.