Prenatal Array Comparative Genomic Hybridization in Fetuses With Structural Cardiac Anomalies.

OBJECTIVES: To examine the diagnostic performance of array comparative genomic hybridization (CGH) for fetal cardiac anomalies in two medium-sized Canadian prenatal genetics clinics. METHODS: We prospectively recruited 22 pregnant women with fetal structural cardiac anomalies, normal rapid aneuploidy detection, and FISH for 22q11.2 testing for array CGH analysis. RESULTS: One case had an 8p deletion that was also visible on karyotype and included the GATA4 gene, which has been associated with congenital heart disease. Two cases had inherited pathogenic copy number variants (CNVs) of variable expressivity and penetrance: one was a duplication of 16p11.2 and the other a deletion of 15q11.2. One case had the incidental finding of being a carrier of a recessive disease unrelated to the cardiac anomaly. CONCLUSIONS: Of these prospectively recruited cases of fetal cardiac anomalies, 14% had a pathogenic result on array CGH. Pathogenic CNVs of variable penetrance and expressivity were a significant proportion of the positive results identified. These CNVs are generally associated with neurodevelopmental issues and may or may not have been associated with the fetus' underlying congenital heart disease. Array CGH increases the diagnostic yield in this group of patients; however, certain CNVs remain a challenge for counselling in the prenatal setting.

Correlation of residual amniotic fluid and perinatal outcomes in periviable preterm premature rupture of membranes.

OBJECTIVE: To correlate maternal and fetal outcomes of pregnancies affected by preterm premature rupture of membranes (PPROM) at < 24 weeks' gestational age with the amount of residual amniotic fluid as determined by sonographic evaluation. METHODS: We searched the local maternal-fetal medicine database for the records of all women with PPROM prior to 24 completed weeks of pregnancy. The quantity of residual amniotic fluid determined by ultrasound was recorded and women were separated into two groups: (A) deepest vertical pocket (DVP) ≥ 1 cm, or (B) DVP < 1 cm (severe oligohydramnios). Hospital chart review was undertaken to determine latency to delivery, perinatal death, and maternal complications. Data were analyzed using Fisher exact and Wilcoxon-Mann-Whitney U tests. RESULTS: We identified 31 subjects, of whom nine elected termination of pregnancy (6 in group A, 3 in group B). Six of 10 subjects in group A had a live delivery without neonatal death, whereas only one of 12 subjects in group B had a live delivery (P = 0.020). Additional complications included placental abruption in 63% in group A and 45% in group B, chorioamnionitis in 50% and 70%, respectively, and postpartum endometritis in 0% and 9%, respectively. None of these differences were statistically significant. There were no cases of maternal sepsis or maternal death in either group. Group A was associated with a later GA at delivery (27.5 weeks vs. 23 weeks, P = 0.07), with the GA at rupture of the membranes similar for both groups. CONCLUSION: These results indicate that a higher level of residual amniotic fluid after periviable PPROM is associated with fetal survival and increased latency to delivery without an increase in maternal complications. This information will be valuable in counselling pregnant women with PPROM < 24 weeks.

The predictive value of 18 and 22 week uterine artery Doppler in patients with low first trimester maternal serum PAPP-A.

OBJECTIVE: To determine if the addition of uterine artery (UA) Doppler pulsatility index (PI) at 18 and 22 weeks of gestation improves the predictive accuracy of low first trimester pregnancy associated plasma protein A (PAPP-A) in the detection of adverse obstetrical outcomes. METHODS: This was a prospective interventional study. All women undergoing first trimester combined screening (FTS) at a single center, with a low maternal serum PAPP-A level (<0.4 MoM), were included. Patients underwent bilateral UA Doppler assessments at 18 and 22 weeks of gestation. A positive test was defined as a mean PI > 1.45. Primary outcomes were obtained from chart review, and logistic regression analysis was used to compare outcomes with positive and negative tests. Positive and negative predictive value, specificity and sensitivity were calculated. RESULTS: Between January and October 2007, 5359 women completed FTS. Among the low PAPP-A group (n = 289), 18 week UA Doppler was a significant predictor of low birth weight (OR = 2.28, p = 0.04) while 22 week UA Doppler significantly predicted preterm birth (OR = 12.6, p = 0.001), small for gestational age (OR = 8.24, p = 0.001) and low birth weight (OR = 2.28, p = 0.04). Test characteristics suggested improved positive and negative predictive value for Doppler at 22 versus 18 weeks for these outcomes. CONCLUSIONS: UA Doppler at 22 weeks is a useful adjunct in patients with low PAPP-A. However, a negative Doppler does not rule out all adverse outcomes and clinical judgment is advised in the management of these patients.