Congenital anomalies: Impact of prenatal diagnosis on mode of delivery

Congenital anomalies: Impact of prenatal diagnosis on mode of delivery

S190 SMFM Abstracts 625 PULMONARY ARTERY MUSCULARIZATION IS REDUCED BY FETAL GLUCOCORTICOIDS (GC) IN LAMBS WITH DIAPHRAGMATIC HERNIA (DH) FOLLOWING TR...

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S190 SMFM Abstracts 625 PULMONARY ARTERY MUSCULARIZATION IS REDUCED BY FETAL GLUCOCORTICOIDS (GC) IN LAMBS WITH DIAPHRAGMATIC HERNIA (DH) FOLLOWING TRACHEAL OCCLUSION (TO) MARCUS DAVEY1, SHINCY SHEGU1, ENRICO DANZER1, EDUARDO RUCHELLI1, N. SCOTT ADZICK1, ALAN FLAKE1, 1 1 HOLLY HEDRICK , Children’s Hospital of Philadelphia, Center of Fetal Research, Philadelphia, Pennsylvania OBJECTIVE: Prenatal GC therapy improves respiratory function in lambs with DH that undergo TO therapy (Davey et al., Ped.Res.2006), which may be due to improved pulmonary vascular structure. In lambs with DH that underwent prolonged TO, we have examined the effects of prenatal GC on muscularization of small pulmonary arteries. STUDY DESIGN: DH was surgically created in 24 fetal sheep at 65 days gestation. TO was performed in 17 of 24 fetuses between 110-140 days; 10 of these fetuses received Betamethasone (0.5mg/kg BW) 48 hours before delivery. 6 Sham-operated animals served as controls. Right lungs were pressure fixed via the trachea with 4% paraformaldehyde-PBS, embedded in paraffin, sectioned (3um) and stained with Elastin-Van Gieson. External diameter (ED) and medial wall thickness (MWT) of small pulmonary arteries were measured (n=629). % MWT was calculated as: (2xMWT/ED)x100. RESULTS: %MWT was increased by DH, and not improved by fetal TO (Figure 1). Average %MWT was significantly lower in GC-treated fetuses compared to non GC-treated animals. CONCLUSION: Prenatal GC reduced aberrant muscularization of pulmonary arteries in lambs that underwent TO therapy for DH. Increased luminal diameter would be expected to reduce pulmonary vascular resistance, and improve gas exchange.

627 CONGENITAL ANOMALIES: IMPACT OF PRENATAL DIAGNOSIS ON MODE OF DELIVERY MARK DEMPSEY1, FIONNUALA M. BREATHNACH1, MICHAEL GEARY2, CHRIS FITZPATRICK3, MICHAEL ROBSON4, FERGAL D. MALONE1, 1Royal College of Surgeons in Ireland, Dublin, Ireland, 2Rotunda Hospital, Dublin, Ireland, 3 Coombe Women’s Hospital, Dublin, Ireland, 4National Maternity Hospital, Dublin, Ireland OBJECTIVE: When an infant does not survive, the consequences of emergency Caesarean section (CS), with its attendant maternal morbidity and implications for subsequent pregnancy, may be far-reaching. We sought to explore congenital anomaly mortality over 10 years in our population to ascertain how prenatal diagnosis impacts on mode of delivery. STUDY DESIGN: A consecutive cohort of 211,163 women, delivered of infants weighing 500g or more in 3 tertiary referral centers from 01/95 to 12/ 04, was analyzed for perinatal death attributed to congenital malformation. Two comparative cohorts were created, comprising diagnosed and undiagnosed anomalies. Women who received no antenatal care and those in whom perinatal death was attributed to an anomaly not amenable to prenatal diagnosis were excluded from the analysis. Continuous data were compared by independent sample t-test and categorical data by chi-square test. RESULTS: Perinatal death attributable to congenital malformation occurred in 692 pregnancies during the study period (incidence 0.33%). The inclusion criteria for this study were met by 634 women. The proportion in whom an anomaly was diagnosed prenatally was 62.1% (394/634). No significant difference was identified between the diagnosed and undiagnosed groups with respect to maternal age, parity, gestation at delivery or infant birth weight. Perinatal death occurred in utero in 37.4% of cases (237/634). In the group that died in the neonatal period, the emergency CS rate was significantly lower where anomaly was detected versus undetected (17.5% vs 31.1%; p = 0.004). In contrast to undiagnosed anomalies, the indication for emergency CS was more often maternal in the diagnosed group (42% vs 19%; p = 0.019). CONCLUSION: An important aspect of prenatal diagnosis is the avoidance of emergency CS in fetal interest in cases where an infant will not survive. Where a diagnosis of congenital anomaly has been made in the prenatal period, the reduction in emergency CS rate by almost half in this study supports a pivotal role for prenatal diagnosis in optimizing maternal care. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.682

0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.679

626 SPLENIC ARTERY DOPPLER IN ALLOIMMUNIZED PREGNANCIES MARIO DIAS CORREA1, MARIO JORGE CASTRO1, ANTONIO CARLOS CABRAL1, HENRIQUE VITOR LEITE1, 1Universidade Federal de Minas Gerais, Departamento de Ginecologia e Obstetricia, Belo Horizonte, MG, Brazil OBJECTIVE: To verify the correlation between fetal splenic artery dopplervelocimetry and fetal hemoglobin levels in Rh alloimmunization and to evaluate the accuracy of this method in the prediction of fetal anemia. STUDY DESIGN: Splenic artery Doppler peak systolic velocity (PSV) and pulsatility index (PI) were obtained before cordocentesis in rhesus alloimmunized fetuses. Doppler was performed before 80 cordocentesis in 36 patients with gestational age between 20 and 35 weeks. Anemia overall was defined as a hemoglobin deficit of ¡Y´ 2g/dL. Moderate and severe anemia were defined as a hemoglobin deficit of ¡Y´ 5 and ¡Y´ 7g/dL respectively. RESULTS: Anemia was noted on 64% of the fetuses and moderate and severe anemia on 18% and 21%. Splenic artery PSV was higher in groups with moderate (p=0,001) and severe (p=0,000) anemia but not in the group with mild anemia (p=0,189) when compared to non anemic fetuses. Splenic artery PI was higher only in the severely anemic group (p=0,001). Splenic artery PSV showed positive correlation with fetal hemoglobin deficit (R2: 27,8%; p=0,000), and so did the splenic artery PI (R2: 8,3%; p=0,000). These findings were most important after 28 weeks gestation. There were no differences among previously transfused fetuses. Sensitivity and specificity in the diagnosis of moderate and severe anemia in the overall group were 45% e 98% and 64% e 96% in fetuses with 28 weeks gestation or more. CONCLUSION: Fetal hemoglobin deficit correlates with splenic artery PSV. This finding is more important in gestations over 28 weeks. The splenic artery PI is higher in fetuses with severe anemia. The accuracy of splenic artery Doppler in the prediction of fetal anemia improves after the 28th week. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.681

628 AUTOMATED ROBOTIC IDENTIFICATION AND ENRICHMENT OF RARE FETAL CELLS IN MATERNAL CIRCULATION (FCMC) MARK EVANS1, MICHAEL KILPATRICK2, TRIANTAFYLLOS TAFAS2, ILIA ICHETOVKIN2, ANTTI SEPPO2, YOUNGMIN KIM2, YANNING ZHU2, PETROS TSIPOURAS2, 1Comprehensive Genetics, New York, New York, 2Ikonisys Inc., New Haven, Connecticut OBJECTIVE: For 20 years, attempts to isolate FCMC suffered from the daunting task of isolating the rare FCMC and inadequate specific markers unique to fetal material. We have developed the Ikonisys fastFISHÔ fully robotic fluorescence microscopy platform, to identify and enumerate cells bearing X and Y FISH signals. More than 4,000 optical fields per slide can be analysed. Previously, we have identified rare XY cells, with a false positive rate below 0.00005%. Here, we have added an enrichment process, to reduce the cell/slide number needed to generate sufficient FCMC for routine clinical testing. STUDY DESIGN: Based on X and centromeric and telomeric-Y FISH signals, the Ikonisys fastFISHÔ system robotically identifies putative fetal cells at 10X magnification which are verified at 100X. 33 maternal samples, 13 first trimester and 20 second trimester, were analysed. Samples were analyzed before and after density gradient centrifugation. RESULTS: Fetal cells were identified in 28 of the 30 samples from pregnancies with male fetuses. For whole blood, 0.3 XY fetal cells per slide (0.5 XY fetal cells per million) were identified. Following simple density gradient enrichment, 1.4 XY fetal cells per slide (2.3 XY fetal cells per million) were identified.

CONCLUSION: FISH with robotic microscopy, identified XY fetal cells in both first and second trimester maternal blood samples. On average, density gradient centrifugation gives a 4-5 fold enrichment over whole blood. Use of specific markers for initial identification of fetal cells could allow analysis of both male and female fetus pregnancies. Our ongoing studies suggest such an approach, integrating ICC or RNA-FISH for fetal cell identification with FISH for chromosome counting, might facilitate non-invasive prenatal diagnosis of chromosomal aneuploidies. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2006.10.683