short telomeres in aneuploidy, intrauterine hypoxia (which causes intrauterine fetal growth restriction [IUGR]), and in uncontrolled gestational diabetes mellitus.
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Academic Issues, Antepartum Fetal, Clinical Ob, Fetus, Genetics, Hypertension, Med-Surg-Diseases, Operative Ob, U/S
Poster Session IV
savings of $2.4 million over 4 years (assuming $459/NT). The false positive rate was 3.9%. CONCLUSION: A stepwise, contingent Down syndrome screening program performed well and saved $2.4 million over 4 years in this cohort. In addition, this approach enabled earlier diagnosis without the need to train and credential large numbers of sonographers.
Algorithm for stepwise, contingent Down syndrome screening
609 Insulin growth factor 1 (IGF-1) therapy restored IUGR induced alteration in pancreatic tissues Khaled Omar1, Tarek Alsaied2, Ahmed Lababidi1, Helen Jones1, Swathi Balaji1, Sundeeb Keswani1, Timothy Crombleholme3, Mounira Habli1 1 Cincinnati Childrens Hospital medical center, Center for molecular fetal therapy, Cincinnati, OH, 2Cincinnati Childrens Hospital medical center, Pediatrics, Cincinnati, OH, 3Colorado Childrens Hospital medical center, Pediatric surgery, Aurora, CO
608 Senescence in genotoxic amniocytes and stressed trophoblasts Tal Biron-Shental1, Moshe Fejgin1, Yehudit Sharon3, Dvora Kidron4, Aliza Amiel2 1 Meir Medical Center, Sackler School of Medicine, Tel Aviv University, Obstetrics and Gynecology, Kfar Saba, Israel, 2Meir Medical Center, Tel Aviv University, Genetic Institute, Kfar Saba, Israel, 3Bar Ilan University, Faculty of Life Science, Ramat Gan, Israel, 4Meir Medical Center, Sackler School of Medicine, Tel Aviv University, Pathology, Kfar Saba, Israel
OBJECTIVE: Cellular senescence is a state of metabolic and cell cycle arrest evoked by exogenous or endogenous stressors, especially genotoxic stress. Some cases of senescence are characterized by formation of senescence-associated heterochromatin foci (SAHF). Short, dysfunctional telomeres lead to senescence. We have previously reported short telomeres in aneuploidy, intrauterine hypoxia (which causes intrauterine fetal growth restriction [IUGR]), and in uncontrolled gestational diabetes mellitus. We studied senescence in amniocytes and placentas from aneuploidic fetuses, in trophoblasts from IUGR fetuses, and from diabetic placentas, by assessing SAHF. STUDY DESIGN: Using DAPI staining, we counted the percentage of cells with increased nuclear fragmentation (SAHF). We assessed SAHF expression in trophoblasts from placental biopsies (n⫽7) and in amniocytes (n⫽10) from known trisomy-21 fetuses and compared the results to control placentas (n⫽6) and to amniocytes (n⫽10) from fetuses with a known normal karyotype. We also assessed the presence of SAHF in trophoblasts from pregnancies complicated by IUGR (n⫽12) and from pregnancies complicated by uncontrolled diabetes mellitus [DM] (n⫽10) and compared them to gestational-agematched controls from uncomplicated pregnancies (n⫽12). RESULTS: A significantly higher rate of cells with SAHF was found in trisomy-21 placentas and amniocytes, as well as in IUGR and in trophoblasts from pregnancies with uncontrolled diabetes compared to the control samples (Figure). CONCLUSION: Increased SAHF formation in amniocytes and in trophoblasts that were previously found to express shorter telomeres emphasizes the correlation between short telomeres and senescence. These findings may be linked to other genetic instability parameters previously described in trisomy-21 and help explain intrauterine programming in pregnancies with IUGR and uncontrolled diabetes mellitus.
OBJECTIVE: We demonstrated that intraplacental gene therapy with adenoviral insulin growth factor (Ad-hIGF1) corrects impaired birthweight and glucose regulatory response in a mouse model of placental insufficiency. Evidence from diabetic patients and Murine IUGR offspring demonstrates decreased area and mass of islets and beta cells. We hypothesized that one of the mechanisms of AdhIGf1 induced attenuation in IUGR related adult onset diabetes is by restoring pancreatic mass, beta and alpha cell ratio. STUDY DESIGN: Laparotomy was performed on pregnant C57BL/6J mice at gestational day 18 and pups were divided into 3 groups (n⫽3). Control: Sham operated; IUGR: by ligation of a branch of mesenteric uterine artery; IGF1-Treated: intra placental injection of Ad hIGF1 after ligation. Pups were delivered on day 20, cross-fostered to CD1 mice. At 32 weeks, Pancreas of the off springs were weighed, and histologically processed and whole mounted. After every 20 section, a 5 um consecutive primary and reference sections were obtained for the entire pancreas. Immunohistochemistry staining was performed for Beta (anti-insulin) and Alpha (anti-glucagon) cells, and area was quantified (design-based stereology). Data were analysed using ANOVA. RESULTS: Male IUGR demonstrated 22% significant reduction in pancreatic mass (230.6 ⫾ 5.8 vs 296 ⫾ 5.7 vs 290⫾ 10 mg, p⫽0.01), 84 % reduction in Islets/Pancreas percentage area (2.5 ⫾ 1.1% vs 14.8 ⫾ 2.6% vs 16 ⫾ 3.7%, p⫽0.02), 80% in Beta cell/Alpha cell percentage area and 12% in Beta cell/ Islets percentage area (Table) as compared to SHAM, which was restored to normal with IGF1 treatment. Total area of pancreas, Islets, beta and alpha cells did not show any significant differences among 3 groups. CONCLUSION: Intra-placental gene transfer of Ad-hIGF1 restored IUGR-induced alterations in pancreatic mass, beta and alpha cell ratio. These changes may represent a potential mechanism of fetal reprogramming by which (AdhIGF1) may attenuate fetal predisposition to adult onset Diabetes.
Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
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Poster Session IV
Academic Issues, Antepartum Fetal, Clinical Ob, Fetus, Genetics, Hypertension, Med-Surg-Diseases, Operative Ob, U/S
Sham as a reference group
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611 Using maternal dry blood spot for fetal DNA quantification, fetal RhD, and fetal gender determination in the first trimester Yali Xiong1, Indhu Prabhakaran1, Eliezer Holtzman2, Stacey Jeronis3, Amen Ness4, Dan Liebermann1, Barbara Hoffman1, Ossie Geifman-Holtzman5 1
Temple University School of Medicine, Fels Institute, Philadelphia, PA, Sheba Medical Center, Tel-Aviv University, Nephrology and Hypertension Institute, Tel Hashomer, Israel, 3Temple University School of Medicine, OBGYN, Philadelphia, PA, 4Saint Peters University Hospital, Drexel University, OBGYN, Philadelphia, PA, 5Drexel University, OBGYN, Philadelphia, PA 2
* ⫽ P ⬍ 0.05; ** ⫽ P ⬍ 0.001.
610 An observational study of a contingency screening program for Down syndrome Valeria Di Stefano1, Elena Ashkinadze1, Revital Faro1, Christy Seymour1, Joaquin Santolaya1, Todd Rosen1 1 UMDNJ-RWJMS, Dept. of Obstetrics, Gynecology and Reproductive Sciences, New Brunswick, NJ
OBJECTIVE: Contingency screening offers similar Down syndrome detection rates to integrated screening with advantages of earlier results and reduced costs as most patients are notified of results in the first trimester. In this study we sought to determine the clinical efficacy of an antenatal contingency genetic screening program. STUDY DESIGN: We reviewed the UMDNJ-RWJMS antenatal genetics database for all patients who participated in the contingency screening program between May 2010 and June 2011. In this program, all women had first trimester screening. If risk returned greater than 1/100 for Down syndrome, genetic counseling was performed and invasive testing was offered. If risk was less than 1/1,000, women were informed they were low risk and offered no further testing. If risk was between 1/100 and 1/1,000, patients were told they were at intermediate risk and scheduled for second trimester serum screening. In the intermediate risk group, numerical risk was not disclosed until the screen was completed, unless the patient requested results. We modeled that 1.8% of women would screen positive in the first trimester, with 1% of women screening positive after second trimester screening. RESULTS: 1634 patients, including 45 twin pregnancies, participated in this program. Table 1 summarizes the performance of the contingency screening program in practice. Not all women followed the prescribed protocol. 20% (38/191) of women in the intermediate risk group requested and received their numerical risk before second trimester blood work was drawn. Of these women, 53% (20/38) completed the second trimester blood work and 18% (7/38) chose an invasive procedure based on the first trimester results. 50% (3/6) of women choosing an invasive procedure were in the traditional screennegative range. CONCLUSION: We implemented a large scale contingency screening program for Down syndrome. 20% of women requested a numerical risk after an intermediate result and were unwilling to wait for the second trimester screen to be completed.
Table
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OBJECTIVE: To determine fetal gender, RhD genotyping and fetal DNA quantification during first screen using peripheral maternal dry blood spot. STUDY DESIGN: Fetal DNA was extracted from both Guthrie card and peripheral blood samples of RhD-negative pregnant in the first trimester. Probe specific Realtime PCRs were used to detect fetal gender gene (male -DSY14, female - S05, S06 and S10A) and Exon 4-6 of the RhD gene. Confirmation was obtained after delivery. Both Simplex (S) and Duplex (D) realtime PCRs were performed for quantification of fetal DNA. RESULTS: RhD amplification of exon 4, 5 or 6 was determined 8/13 and 5/13 fetuses to be Rh-positive or Rh-negative, respectively. One Rhnegative baby was incorrectly diagnosed as positive. Except for one, sex determination was correct in all cases. Quantification studies using S PCR and ratio of expressional levels of fetal gender genes over the -actin levels detected fetal DYS14 gene: positive, ratio⫽ 3.45814893 from mononuclear layer and 0.00445611 from Guthrie card. Using D PCR and ratio of expressional levels of fetal gender genes (female) and RhD gene over the predetermined copy number gene levels detected fetal female polymorphism gene S06: positive, copy number⫽ 1.254070363 and RhD gene exon4 copy number⫽ 6.601552872, exon5 copy number⫽ 9.003016417, exon6 copy number⫽11.21182. CONCLUSION: Our study revealed that fetal DNA from maternal dry blood samples placed on Guthrie card during the first trimester screen were reliable sources for fetal sex and fetal RhD determination as well as fetal DNA quantification. Although this method is prospective for convenient testing, fetal DNA trace from previous pregnancy may impair the accuracy of the results. Fetal DNA quantification has the potential in clinical use not only for accurate fetal genotyping but also for numerous applications such as predicting anomalies & pregnancy complications in the current pregnancy, early in the first trimester.
612 Low-dose aspirin is associated with a reduction in spontaneous preterm birth among non-smokers Adi Abramovici1, Victoria Jauk1, Luisa Wetta1, Rodney Edwards1, Joseph Biggio1, Alan Tita1 1 University of Alabama at Birmingham, Obstetrics and Gynecology, Birmingham, AL
OBJECTIVE: To evaluate the relationship between prenatal low dose aspirin intake and perinatal outcomes in high risk women when stratified by smoking status. STUDY DESIGN: Secondary analysis of a NICHD MFMU multi-center placebo-controlled trial of low-dose (60mg) aspirin to prevent preeclampsia in women at high risk (prior preeclampsia, chronic hypertension, diabetes mellitus or multifetal pregnancy). We examined the effect of aspirin intake by reported smoking status (smokers and nonsmokers). The primary outcome was preeclampsia. Secondary perinatal outcomes included preterm birth, birthweight ⬍2500 grams, and neonatal intensive care unit (NICU) admission. The Breslow-Day test was used to ascertain differences in results by smoking status. RESULTS: Of the 2500 women, 1252 received aspirin and 1248 received placebo. The prevalence of treatment assignment (aspirin) was similar between smokers (50.8%) and non-smokers (49.9%). The analyses of aspirin by smoking status for select perinatal outcomes are in the
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013
