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Oral Concurrent Session 4 Physiology/Genetics www.AJOG.org

49 The association between preterm delivery andong term maternal cardiovascular morbidity

Roy Kessous1, Gali Pariente1, Carmit Erez-Azulay1, Ilana Shoham-ardi2, Gershon Holcberg1, Eyal Sheiner1

1Soroka University Medical Center, Ben-Gurion University of the Negev,epartment of Obstetrics and Gynecology, Faculty of Health Sciences, Beer

heva, Israel, 2Ben-Gurion University of the Negev, Epidemiology and Healthervices Evaluation, Beer sheva, Israel

OBJECTIVE: To investigate whether a history of preterm deliveryPTD) poses a risk for subsequent maternal long term cardiovascularorbidity.

STUDY DESIGN: A population-based study comparing consecutivepregnancies of women with and without a diagnosis of PTD was con-ducted. Deliveries occurred during the years 1988-1999 and had afollow up until 2010. Incidence of long-term cardiovascular hospital-izations and morbidity was compared between women with PTD andwomen who gave birth at the same period without PTD. Multivariableanalysis was used to control for ethnicity and maternal age.RESULTS: During the study period 47908 deliveries met the inclusionriteria; 12.5% (n�5992) occurred in patients who were diagnosedith PTD. During a follow up period of more than ten years, patientsith PTD were more likely to have simple and complex cardiovascular

vents. In addition, patients with PTD had higher rates of long-termardiovascular hospitalizations (table). Using a multivariable logisticegression model, controlling for confounders such as maternal agend ethnicity, PTD remained an independent risk factor for long-erm maternal cardiovascular hospitalizations (adjusted OR� 1.6;5% CI-1.4-1.9, p � 0.001).

CONCLUSION: Preterm delivery is an independent risk factor for long-term cardiovascular morbidity in a follow-up period of more than adecade.

50 Genomic profiles in common aneuploidies:combination of dose effects and whole

enome misregulationKatherine Bianco1, Matthew Gormley1, Hannah Tilden1,

ike McMaster1, Susan Fisher1

1UCSF School of Medicine, Obstetrics, Gynecology &eproductive Sciences, San Francisco, CA

OBJECTIVE: Trisomy 21, 18 and 13 (T21, T18, T13) are the most com-on aneuploidies, and therefore, the main focus of pregnancy screen-

ng. We sought to improve understanding at the molecular level ofhese entities.

STUDY DESIGN: 20 placentas biopsies from trisomy cases (T21,n�10;18,n�6;T13,n�4) & 4 gestational age-matched, euploid con-

rols(14-22 wks) were collected. FISH was used to confirm the ploidy.lobal transcriptional profiling was used to compile genes that wereifferentially expressed (DE). DE genes were validated by qRT-PCR.tatistical significance was set at p-value � 0.05.

RESULTS: We identified genes that were (DE) inT21(n�130; 120regulated,102regulated),T18 (n�75; 69 1regulated, 5 2regu-

lated) & T13 (n�74; 66 1regulated, 8 2regulated). Our findingssupported the hypothesis that there is a gene “dosing” effect as severalof the over expressed genes resided on the corresponding aneuploidchromosome. For T18, the most highly1-regulated genes were glu-taminyl-peptide cyclotransferase (GPTC) & sperm specific antigen 2(SSFA2). For T21, SSFA2 was the most highly1regulated gene. Thisfinding suggested the existence of more complicated mechanisms ofregulation beyond gene dosing, perhaps genome-wide phenomena

that result in overlapping patterns of gene expression in trisomies that

S30 American Journal of Obstetrics & Gynecology Supplement to JANUARY 20

involve different chromosomes. Other1 regulated genes in T21 in-cluded CASP2 & ADAMTS1. The latter gene, which is located in thepostulated Down syndrome critical region (21q21-22), has been as-sociated with early onset of Alzheimer’s DS. For T13 the top1 regu-lated genes included GALNT7, IL13RA1,IL-18, & IGFBP5, which wasalso 1regulated in T18. Interestingly, IGFBP5 is proteolyzed byPAPP-A during pregnancy, resulting in 1 IGF bioviability, whichmay have consequence for the development of the fetal/maternal unit.CONCLUSION: Improving our knowledge of the molecular conse-quences of the most common aneuploidies has the potential to yieldbetter diagnostic/ therapeutic approaches.

51 Moderate voluntary running protects against hepaticnsulin resistance and restores the placenta-pup glucoseptake gradient in diet-induced obese pregnant rats

Hye Heo1, Derek Huffman2, Fabien Delahaye1, Scarlett Karakash1,ongmei Zhao1, Nir Barzilai2, Francine Einstein1

1Montefiore Medical Center/Albert Einstein College of Medicine,bstetrics & Gynecology and Women’s Health, Bronx, NY, 2Montefioreedical Center/Albert Einstein College of Medicine, Medicine

nd Genetics, Bronx, NYOBJECTIVE: To evaluate the effects of voluntary running on insulinction and placenta/pup glucose uptake in lean and diet-inducedbese pregnant rats.

STUDY DESIGN: Age-matched pregnant SD rats were studied (n�5-6/group): lean exercise (LE), lean sedentary (LS), obese (western dietfrom 3wks through gestation) exercise (OE), and obese sedentary(OS). Starting D1 of 22-day gestation, LE and OE were individuallycaged with voluntary running wheels. On D19, hyperinsulinemic-eu-glycemic clamps (3mU/kg/min) were performed using 33H-glucosetracer to asses insulin sensitivity and 2-[U-14C]deoxyglucose for tis-sue uptake. To study chronic effects of exercise, wheels were locked18hrs prior to clamp studies. Tissue samples were weighed and col-lected at the end of the clamp.RESULTS: Compared to lean, obese dams weighed more pre-preg-

ancy (285�3 v 274�6g, p�0.05) and had more visceral fat (13�1 v�1g, p�0.05). Body weight, visceral fat and food intake remainedimilar with exercise. Plasma free fatty acids, triglycerides, liver tri-lyceride, total glycolysis, and total glycogen synthesis were similar inll groups. LE and OE ran similar total distances during pregnancy9,433�1,593 v 14,966�3,221m, p�NS). OE had improved hepaticnsulin sensitivity compared to OS as demonstrated by decreased

GP (Table 1). LS and LE had similar peripheral and hepatic insulinensitivity. 2-deoxyglucose uptake in placenta compared to pups wasignificantly greater in LS and LE. This placenta-pup gradient wasliminated in OS and restored with exercise (OE) (Fig 1). Pup weight,itter size and placenta weight (adjusted for litter size) were similar inll groups.

CONCLUSION: Maternal voluntary running improves hepatic insulinsensitivity in diet induced obese rats, but has no effect on lean dams.Voluntary running in pregnancy restores the normal gradient of pla-centa-pup glucose uptake, which is disrupted with maternal diet-in-duced obesity.

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www.AJOG.org Physiology/Genetics Oral Concurrent Session 4

52 Maternal plasma DNA sequencing: effects ofultiple gestation on aneuploidy detection and the

elative cell-free fetal DNA (cffDNA) per fetusAnupama Srinivasan1, Diana Bianchi2, Wayne Liao3,

my Sehnert3, Richard Rava1

1Verinata Health, Inc., Research and Development, Redwood City, CA,2Tufts Medical Center, Mother Infant Research Institute, Boston, MA,3Verinata Health, Inc., Clinical Affairs, Redwood City, CAOBJECTIVE: Aneuploidy determination by massively parallel sequenc-

2-deoxyglucose uptake byplacenta compared to pups

Mean � SD.*P � .05 placenta vs pup was significantly greater in both LS and LE. Placenta-pup gradient waseliminated in OS and restored with exercise (OE).

Hyperinsulinemic euglycemic clamps

*P � .05 compared to OS.

ng (MPS) is limited only by the counting statistics of the sequencing

Supplem

process. At the depth of sequencing currently being utilized in clinicallaboratories, the fetal fraction of the total DNA required to exceedstatistical thresholds is 2-4% depending on the chromosome beinganalyzed. The objectives of this study were to determine the ability ofMPS to detect fetal aneuploidy in multiple gestations, and to investi-gate the relative fraction of cffDNA per fetus.STUDY DESIGN: Plasma samples from 84 women originally enrolled inthe MELISSA study (Bianchi et al, 2012) but excluded due to multiplegestation were sequenced blindly and classified for chromosomes(chr) 21, 18, 13, and sex using normalized chromosome values(NCVs) as previously described for singletons. NCVs for chr X insamples with at least one male fetus were used to determine thecffDNA fraction per fetus.RESULTS: There were 66 sets of dichorionic twins, 9 monochorionicwin sets, 7 triplets, and 2 quadruplets. Aneuploidy was correctly de-ected for chr 21 in 1 dichorionic twin pair and for chr 18 in 1 set of

onochorionic twins with no false positives. There were no false neg-tives. Measurements of the cffDNA fraction in the twins and tripletsased on NCVs for chr X allowed determination of fetal fraction peretus (Table). Using 48 samples with dichorionic twins and at least one

ale fetus, the mean fetal fraction was 6.5% (SD 2.5%) with a rangerom 1.6% to 15.9% per fetus. There was no significant dependence ofetal fraction on GA in the range examined (10-23 weeks)R2�0.0006, p�0.717) for these samples.

CONCLUSION: The relative cffDNA fraction per fetus is reduced in mul-tiple compared to singleton gestations. Detection of fetal aneuploidyin twin gestations by maternal plasma DNA sequencing is possible,with very low false positive rates.

Fetal fraction in multiple gestation pregnancieswith male fetus

ent to JANUARY 2013 American Journal of Obstetrics & Gynecology S31