708: maternal tobacco use and maternal obesity alter mitochondrial dna in placental tissue

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termination, 103 (22.7%) were born alive (6% of them with Down’s syndrome), 67 (14.8%) miscarried before 24 weeks, 5 (1.1%) had fetal loss after 24 weeks and 2 (0.4%) suffered neonatal death. Of the elec- tively terminated pregnancies we found that 76 (27.5%) had a normal karyotype, 148 (53.6%) had an abnormal karyotype, and no karyotype was available for 52 (18.8%) subjects. Of all genetic abnormalities, Trisomy 21 (32.4%) was the most frequently detected, followed by Monosomy X and Trisomy 18 (23.6% each). Trisomy 13 was detected in 8% while Mosaicism and Triploidies were both diagnosed in 2%. 8% had other abnormal karyotypes. CONCLUSIONS: Many pregnant women (60%) diagnosed with cystic hygroma terminate their pregnancy. A significant percentage (27.5%) of those terminations have a normal karyotype. 705 Neural tube defects and growth restriction: is there an association? Shayna Norman 1 , Anthony Odibo 1 , Ryan Longman 1 , Kimberly A. Roehl 1 , George Macones 1 , Alison Cahill 1 1 Washington University in St. Louis, St. Louis, MO OBJECTIVE: To estimate the association between neural tube defects (NTD) and intrauterine growth restriction (IUGR). STUDY DESIGN: This was a retrospective cohort study of consecutive women undergoing ultrasound from 17-22 weeks for anatomic survey with a singleton gestation at one institution from 1990 to 2008. Pres- ence or absence of a fetus with a NTD, excluding anencephaly, defined the two study groups. The primary outcomes were IUGR defined as birth weight 10 th percentile, and severe IUGR defined as birth weight 5 th percentile. Subgroup analysis was performed for isolated NTD to observe if the association with IUGR persisted. Univariate, bivariate, and multiple logistic regression analyses were performed. RESULTS: Among 66,956 women in the cohort, 170 were found to have fetal NTD. Of the 170 women with a NTD, 149 cases were isolated NTD with no other major anomalies. At baseline, the only character- istic that differed between the 2 study groups was maternal age; women found to have fetal NTD were significantly younger. Fetuses with a NTD were found to have a significantly increased risk for IUGR 10 th percentile and severe IUGR 5 th percentile, and the associa- tion persisted even when the finding of NTD was isolated. (Table 1) CONCLUSIONS: Women found to have a fetal NTD are at increased risk for IUGR even when the NTD is an isolated finding. The findings suggest that a policy of serial growth scans in cases with isolated NTD is justified. Table 1. Association between isolated NTD and IUGR Isolated NTD Present (n149) NTD Absent (n66786) RR (95% CI) aOR* (95% CI) P value IUGR 10% 18.1% 8.3% 2.2 2.4 0.01 .......................................................................................................................................................................................... (n5642) (1.6-3.1) (1.5-3.6) .......................................................................................................................................................................................... IUGR 5% 14.1% 6.3% 2.2 2.3 0.01 .......................................................................................................................................................................................... (n4265) (1.5-3.3) (1.5-3.7) .......................................................................................................................................................................................... * Adjusted for advanced maternal age, African-American race, smok- ing, and chronic hypertension † No other major congenital anomalies identified 706 Electrical uterine myography (EUM) is as good as intra uterine pressure catheter (IUP) in measuring contractions Gabi Haran 1 , Moshe D Fejgin 1 , Tal Biron-Shental 1 1 Meir Medical Center, Tel Aviv University, Kfar Saba OBJECTIVE: Electrical uterine myography (EUM) enables noninvasive measuring of uterine contractions. Unlike the external commonly used monitor, the EUM is capable of evaluating the intensity of the contractions. Nowadays, whenever this parameter is crucial during labor, intra uterine pressure catheter (IUP) is used. Since IUP is inva- sive, requires ruptured membranes and might increase infections and bleeding, an accurate noninvasive tool to measure contractions is ben- eficial. The aim of this study was to determine the accuracy of the EUM in evaluating contraction compared to IUP. STUDY DESIGN: EUM was measured prospectively on 10 women in different stages of labor. Subjects were monitored simultaneously by an IUP monitor. Myometrial electrical activity was measured using a multi-channel amplifier and a 3-dimensional non-invasive position sensor. Data evaluator was blinded to clinical parameters. Energy was presented in units of micro-Watts and was compared to IUP. We compared the intensity, the length and the frequency of uterine con- tractions between the two methods. Usage of IUP was made only according to clinical indications. RESULTS: Pearson analysis showed complete correlation between the EUM and the IUP in terms of timing, length and intensity of the contractions (P0.0001). CONCLUSIONS: EUM is as good as IUP for evaluating contractions dur- ing labor. Since EUM is noninvasive, it might be even beneficial. 707 Mechanisms of telomere shortening in placentas from pregnancies complicated with intrauterine growth restriction Tal Biron-Shental 1 , Rivka Sukenik-Halevy 2 , Moshe D Fejgin 1 , Reuven Sharony 1 , Dvora Kidron 3 , Aliza Amiel 4 1 Meir Medical Center, Tel Aviv University, Kfar Saba, 2 Meir Medical Center, Kfar Saba, 3 Meir Medical Center, Tel Aviv Uniersity, Kfar Saba, 4 Genetic Institute, Meir Medical Center, Bar Ilan University, Kfar saba OBJECTIVE: Intrauterine Growth Restriction (IUGR) correlates with placental telomere shortening and senescence. Telomerase is an en- zyme complex that elongates telomeres. Telomerase RNA component (TERC) gene serves as the RNA template for the addition of telomeric repeats. Telomerase reverse transctiptase (TERT) is the catalytic com- ponent of telomerase. We studies mechanisms of telomere shortening in IUGR placentas. STUDY DESIGN: We estimated the copy number of the TERC gene us- ing FISH and the expression of TERT mRNA using RT-PCR, in pla- cental biopsies from six pregnancies complicated with IUGR and from six gestational age matched controls. RESULTS: Lower TERC gene copy number was observed in IUGR tro- phoblasts (p0.05). TERT mRNA was found to be diminished in IUGR placentas compared to control samples (mean fold of 0.50.2 and 0.960.1 respectively, p0.0005). CONCLUSIONS: These results support and explain the observations of telomere shortening and decreased telomerase activity in IUGR pla- centas. We suggest that these findings may play a role in the patho- physiology of IUGR, perhaps by promoting senescence in tropho- blasts of IUGR placentas. 708 Maternal tobacco use and maternal obesity alter mitochondrial DNA in placental tissue Adi Abramovici 1 , Lauren Patterson 1 , Behrouz Zand 1 , Cynthia Shope 1 , Min Hu 1 , Lori Showalter 1 , Melissa Suter 1 , Kjersti Aagaard 1 1 Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TX OBJECTIVE: Maternal adipose tissue contributes to an inflammatory response, providing a potential source of oxidative stress on the pla- centa. Maternal smoking leads to the activation of phase I enzymes in the placenta, which process xenobiotics into reactive unstable inter- mediates and expose the cell to increased oxidative stress. We hypoth- esized that increased oxidative stress related to maternal tobacco use or obesity may lead to associative altered mitochondrial DNA (mtDNA) copy number, as well as the highly variant D-loop segment of the mitochondrial genome (Figure). STUDY DESIGN: Placentas were stored at 80°C within 30 minutes of delivery until use. Nuclear DNA, RNA, and mtDNA was extracted from each of three nested cohorts: smokers (SP, N20), class II/III obese(OP, n18), and their 1:1 matched controls (matched by ma- www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging Poster Session V Supplement to JANUARY 2011 American Journal of Obstetrics & Gynecology S279

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Page 1: 708: Maternal tobacco use and maternal obesity alter mitochondrial DNA in placental tissue

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www.AJOG.org Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging Poster Session V

termination, 103 (22.7%) were born alive (6% of them with Down’ssyndrome), 67 (14.8%) miscarried before 24 weeks, 5 (1.1%) had fetalloss after 24 weeks and 2 (0.4%) suffered neonatal death. Of the elec-tively terminated pregnancies we found that 76 (27.5%) had a normalkaryotype, 148 (53.6%) had an abnormal karyotype, and no karyotypewas available for 52 (18.8%) subjects. Of all genetic abnormalities,Trisomy 21 (32.4%) was the most frequently detected, followed byMonosomy X and Trisomy 18 (23.6% each). Trisomy 13 was detectedin 8% while Mosaicism and Triploidies were both diagnosed in 2%.8% had other abnormal karyotypes.CONCLUSIONS: Many pregnant women (60%) diagnosed with cystic

ygroma terminate their pregnancy. A significant percentage (27.5%)f those terminations have a normal karyotype.

705 Neural tube defects and growthestriction: is there an association?

Shayna Norman1, Anthony Odibo1, Ryan Longman1,imberly A. Roehl1, George Macones1, Alison Cahill1

1Washington University in St. Louis, St. Louis, MOOBJECTIVE: To estimate the association between neural tube defectsNTD) and intrauterine growth restriction (IUGR).

STUDY DESIGN: This was a retrospective cohort study of consecutiveomen undergoing ultrasound from 17-22 weeks for anatomic surveyith a singleton gestation at one institution from 1990 to 2008. Pres-

nce or absence of a fetus with a NTD, excluding anencephaly, definedhe two study groups. The primary outcomes were IUGR defined asirth weight � 10th percentile, and severe IUGR defined as birtheight � 5th percentile. Subgroup analysis was performed for isolatedTD to observe if the association with IUGR persisted. Univariate,ivariate, and multiple logistic regression analyses were performed.

RESULTS: Among 66,956 women in the cohort, 170 were found to haveetal NTD. Of the 170 women with a NTD, 149 cases were isolatedTD with no other major anomalies. At baseline, the only character-

stic that differed between the 2 study groups was maternal age;omen found to have fetal NTD were significantly younger. Fetusesith a NTD were found to have a significantly increased risk for IUGR10th percentile and severe IUGR �5th percentile, and the associa-

ion persisted even when the finding of NTD was isolated. (Table 1)CONCLUSIONS: Women found to have a fetal NTD are at increased riskor IUGR even when the NTD is an isolated finding. The findingsuggest that a policy of serial growth scans in cases with isolated NTDs justified.

Table 1. Association between isolated NTD and IUGR

Isolated† NTDPresent(n�149)

NTD Absent(n�66786)

RR(95%CI)

aOR*(95%CI) P value

UGR10%

18.1% 8.3% 2.2 2.4 �0.01

..........................................................................................................................................................................................

(n�5642) (1.6-3.1) (1.5-3.6)..........................................................................................................................................................................................

IUGR �5% 14.1% 6.3% 2.2 2.3 �0.01..........................................................................................................................................................................................

(n�4265) (1.5-3.3) (1.5-3.7)..........................................................................................................................................................................................

* Adjusted for advanced maternal age, African-American race, smok-ing, and chronic hypertension † No other major congenital anomaliesidentified

706 Electrical uterine myography (EUM) is as good as intraterine pressure catheter (IUP) in measuring contractions

Gabi Haran1, Moshe D Fejgin1, Tal Biron-Shental11Meir Medical Center, Tel Aviv University, Kfar SabaOBJECTIVE: Electrical uterine myography (EUM) enables noninvasive

easuring of uterine contractions. Unlike the external commonlysed monitor, the EUM is capable of evaluating the intensity of the

ontractions. Nowadays, whenever this parameter is crucial during o

Supplem

labor, intra uterine pressure catheter (IUP) is used. Since IUP is inva-sive, requires ruptured membranes and might increase infections andbleeding, an accurate noninvasive tool to measure contractions is ben-eficial. The aim of this study was to determine the accuracy of theEUM in evaluating contraction compared to IUP.STUDY DESIGN: EUM was measured prospectively on 10 women in

ifferent stages of labor. Subjects were monitored simultaneously byn IUP monitor. Myometrial electrical activity was measured using aulti-channel amplifier and a 3-dimensional non-invasive position

ensor. Data evaluator was blinded to clinical parameters. Energy wasresented in units of micro-Watts and was compared to IUP. Weompared the intensity, the length and the frequency of uterine con-ractions between the two methods. Usage of IUP was made onlyccording to clinical indications.

RESULTS: Pearson analysis showed complete correlation between theUM and the IUP in terms of timing, length and intensity of theontractions (P�0.0001).

CONCLUSIONS: EUM is as good as IUP for evaluating contractions dur-ng labor. Since EUM is noninvasive, it might be even beneficial.

707 Mechanisms of telomere shortening in placentas fromregnancies complicated with intrauterine growth restriction

Tal Biron-Shental1, Rivka Sukenik-Halevy2, Moshe D Fejgin1,euven Sharony1, Dvora Kidron3, Aliza Amiel4

1Meir Medical Center, Tel Aviv University, Kfar Saba, 2Meir Medical Center,Kfar Saba, 3Meir Medical Center, Tel Aviv Uniersity, Kfar Saba, 4GeneticInstitute, Meir Medical Center, Bar Ilan University, Kfar sabaOBJECTIVE: Intrauterine Growth Restriction (IUGR) correlates with

lacental telomere shortening and senescence. Telomerase is an en-yme complex that elongates telomeres. Telomerase RNA componentTERC) gene serves as the RNA template for the addition of telomericepeats. Telomerase reverse transctiptase (TERT) is the catalytic com-onent of telomerase. We studies mechanisms of telomere shortening

n IUGR placentas.STUDY DESIGN: We estimated the copy number of the TERC gene us-ing FISH and the expression of TERT mRNA using RT-PCR, in pla-cental biopsies from six pregnancies complicated with IUGR andfrom six gestational age matched controls.RESULTS: Lower TERC gene copy number was observed in IUGR tro-

hoblasts (p�0.05). TERT mRNA was found to be diminished inUGR placentas compared to control samples (mean fold of 0.5�0.2nd 0.96�0.1 respectively, p�0.0005).

CONCLUSIONS: These results support and explain the observations ofelomere shortening and decreased telomerase activity in IUGR pla-entas. We suggest that these findings may play a role in the patho-hysiology of IUGR, perhaps by promoting senescence in tropho-lasts of IUGR placentas.

708 Maternal tobacco use and maternal obesitylter mitochondrial DNA in placental tissue

Adi Abramovici1, Lauren Patterson1, Behrouz Zand1,ynthia Shope1, Min Hu1, Lori Showalter1,elissa Suter1, Kjersti Aagaard1

1Maternal-Fetal Medicine, Baylor College of Medicine, Houston, TXOBJECTIVE: Maternal adipose tissue contributes to an inflammatoryesponse, providing a potential source of oxidative stress on the pla-enta. Maternal smoking leads to the activation of phase I enzymes inhe placenta, which process xenobiotics into reactive unstable inter-

ediates and expose the cell to increased oxidative stress. We hypoth-sized that increased oxidative stress related to maternal tobacco user obesity may lead to associative altered mitochondrial DNAmtDNA) copy number, as well as the highly variant D-loop segmentf the mitochondrial genome (Figure).

STUDY DESIGN: Placentas were stored at �80°C within 30 minutes ofelivery until use. Nuclear DNA, RNA, and mtDNA was extracted

rom each of three nested cohorts: smokers (SP, N�20), class II/III

bese(OP, n�18), and their 1:1 matched controls (matched by ma-

ent to JANUARY 2011 American Journal of Obstetrics & Gynecology S279

Page 2: 708: Maternal tobacco use and maternal obesity alter mitochondrial DNA in placental tissue

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Poster Session V Academic Issues, Antepartum Fetal Assessment, Genetics, Hypertension, Medical-Surgical Complications, Ultrasound-Imaging www.AJOG.org

ternal BMI, ethnicity, and gestational age; CP, n�20). Nuclear DNA,mtDNA, and D-Loop copy number/variant was quantitiated by ratiomeasurements (16S, 18S, tRNA, mtDNA, and normalization) withSybr. Gene expression analysis was performed using qPCR with Taq-Man probes.RESULTS: D-Loop variant, normalized to nuclear 18S DNA, differed

etween CP and OP (1.5-fold increase, p�0.004) but not between CPnd SP (1.33-fold, p�0.369). Similarly, we observed a significant dif-erence in mtDNA copy number between CP and SP (1.12-fold,�0.021) but not between CP and OP (1.19-fold, p�0.440). Al-hough we tested expression levels in all 58 subjects of 10 integraluclear encoded transcripts, we did not observe a significant differ-nce in expression of nuclear genes regulating mitochondrial functionp.0.05).

CONCLUSIONS: We demonstrate a signficant increase in placentaltDNA copy number among smokers, alongside an increase in theitochondrial D-Loop variant in obese subjects. Given our prior

ndings on the role of epigenetic modifications in mediating placentalene expression among smokers, we speculate that altered mtDNAopy number may serve as an additional non-nuclear genomic adap-ive response to the metabolic and oxidative demands from maternalmoking and obesity.

709 The impact of first trimester risk assessment on timingf aneuploidy diagnosis and termination of pregnancy

Asha Heard1, Laura Baecher-Lind1,lison Monahan1, Sabrina Craigo1

1Tufts Medical Center, Boston, MAOBJECTIVE: Over the past decade there has been increasing availabilitynd acceptance of aneuploidy screening using first trimester markers.

e sought to evaluate the impact of first trimester risk assessment onhe gestational age at time of invasive testing for and at termination ofregnancy for aneuploidy.

STUDY DESIGN: All cases of aneuploidy diagnosed antenatally at a ter-tiary care referral center from January 2002 to December 2009 wereincluded for analysis. Gestational age at time of invasive diagnosticprocedure, indications for invasive testing, and gestational age at ter-mination of pregnancy were collected. First trimester risk assessmentwas defined as first trimester serum screening or first trimester ultra-sound. The association between gestational age at time of invasivetesting and at subsequent termination of pregnancy was analyzed us-ing Pearson’s pairwise correlation coefficients. Linear regression wasused to analyze continuous variables over time.RESULTS: 272 patients had complete clinical data and abnormal fetal

aryotypes. Of these patients, 181 (67%) underwent subsequent ter-ination of pregnancy. Gestational age at time of invasive testing and

estational age at termination were significantly correlatedp�0.002). Gestational age at invasive testing and at termination of

regnancy decreased over time. This corresponded to a 7% increase a

S280 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2

per year in the proportion of cases of aneuploidy diagnosed by CVSrather than amniocentesis (p�0.01). Similarly, the proportion of an-euploidy cases diagnosed due to abnormal first trimester risk assess-ment significantly increased by 5% per year (p�0.02). From 2002-2009, the gestational age at time of invasive testing decreased by 2.3days per year (p�0.05) and the gestational age at termination of preg-nancy for aneuploidy decreased by 2 days per year (p�0.07).CONCLUSIONS: These findings demonstrate an intended goal of firstrimester screening can be achieved. Increasing use of first trimesterisk assessment is associated with an earlier gestational age at aneu-loidy diagnosis and affords patients earlier options for terminationf pregnancy.

710 Inflammatory cytokines patternn recurrent miscarriage

Stefano R. Giannubilo1, Beatrice Landi1, Valentina Pozzi1,affaella Raffio1, Davide Sartini1, Monia Cecati1,iergiorgio Stortoni1, Alessandra Corradetti1,ndrea L. Tranquilli1, Monica Emanuelli1

1Universita’ Politecnica Marche, AnconaOBJECTIVE: To elucidate the role of inflammatory processes involvedn alloimmune activation, at placental interface, in the pathophysiol-gy of recurrent miscarriage.

STUDY DESIGN: We investigated the expression pattern of inflamma-ory cytokines and their receptors in trophoblastic tissue from womenith unexplained recurrent spontaneous miscarriage. Trophoblastic

issue was obtained during surgical uterine evacuation in 11 womenith recurrent miscarriage and in 20 healthy pregnant women under-oing elective termination of pregnancy as controls. The array waserformed with GEArray Q Series Human Inflammatory Cytokines &eceptors Gene Array HS-015 membranes. The data were confirmedy quantitative real-time PCR (qPCR). The Mann-Whitney U test waserformed for statistical analysis.

RESULTS: Macroarray analysis identified three genes differentially ex-ressed. Quantitative real-time PCR in trophoblastic tissue confirmedsignificant down-regulation for Transforming Growth Factor beta 3

TGF- �3) and for Interleukin 25 ( IL-25) (5-fold reduction and 2.5-fold reduction, respectively), and a significant up-regulation for CD-25, also known as Interleukin 2 receptor alpha (IL-2RA) (7-fold in-crease) in women with recurrent miscarriage compared to controls.CONCLUSIONS: These results seem to suggest that immunological andnflammatory regulation of the placental environment plays a key rolen unexplained recurrent miscarriage. The trophoblast cytokines ex-ression pattern confirm a switch between Th1 and Th2 profile ataternal-fetal interface, in recurrent miscarriage, consistently with

he immunotrophic theory.

711 Prenatal genetic invasive procedures: experiencever a 10-years period in a single private center

Carmen Comas Gabriel1, Monica Echevarria Telleria1, M Angelesodriguez Perez1, Ana Munoz Prades1, Margarita Torrents Muns1

1Institut Universitari Dexeus, BarcelonaOBJECTIVE: To describe invasive prenatal diagnostic practice in a sin-le-center over a 10-years period.

STUDY DESIGN: Included in this study were all consecutive pregnancieswith genetic amniocentesis (AC) or chorionic villus sampling (CVS)procedure done during the period January 1999 to December2008.Invasive procedures were performed by 10 obstetricians experi-enced in obstetric ultrasound. All tests were performed under ultra-sound guidance. CVS were done transvaginally (by Snake forceps).RESULTS: A total of 8928 AC and 412 CVS were performed (9% in

ultiple pregnancies). Main indications for referral were increasedaternal age (38%) and anxiety (24%). The mean gestational age inhich de procedure was done was 15,9 (range 10-38) in AC and 11,6eeks (range 9-16) in CVS. The mean MA was 35 (range 16-48). In

his series, 380 cases of chromosome abnormalities (CA) were detect-

ble by conventional cytogenetic analysis (4,1%), 269 of them consid-

011