44: the effect of pregnancy on long-term maternal cardiovascular function in a mouse model of...

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PHYSIOLOGY/GENETICS Abstracts 44 – 52 Moderators: William Gilbert, MD; Jim Goldberg, MD 44 The effect of pregnancy on long-term maternal cardiovascular function in a mouse model of pre-pregnancy obesity Egle Bytautiene 1 , Esther Tamayo 1 , Huazhi Yin 1 , Phyllis Gamble 1 , George Saade 1 1 University of Texas Medical Branch, Obstetrics and Gynecology, Galveston, TX OBJECTIVE: The prevalence of pre-existing obesity in the pregnant population continues to increase. Obesity itself is associated with ad- verse cardiovascular outcomes later in life, and pregnancy may com- pound this risk. The objective of our study was to evaluate whether pregnancy increases the risk of cardiovascular abnormalities later in life beyond the risks associated with pre-pregnancy obesity, using a well characterized animal model. STUDY DESIGN: Virgin CD-1 female mice were placed on standard (SF) or high fat (HF) diet. After 3 months, mice were randomly allocated to a breeding versus non breeding group resulting in 4 groups: primi- gravid on SF (SF-PG) or HF (HF-PG) and nulligravid on SF (SF-NG) or HF (HF-NG). The primigravid group proceeded through a normal pregnancy and delivery. After weaning of the primigravid group, all animals were contemporaneously placed on SF diet. At 6 months post partum, PG mice were age-matched to NG mice and fitted with te- lemetric transducers for systolic (SBP) and diastolic blood (DBP) pressure recordings in the conscious, unrestrained animals. Student t-test and Mann-Whitney test were used for statistical analysis (sig- nificance: p0.05). RESULTS: There were no differences in BP between nulligravid HF and SF mice. The primigravid HF mice exposed to pregnancy had signif- icantly higher SBP (p0.04) than SF-PG mice. Comparisons within diet groups revealed that SF-NG had significantly higher SBP (p0.03) and DBP (p0.04) than SF-PG mice (Figure A). HF-NG group exhibited significantly higher DBP (p0.03) and a trend to- wards higher SBP compared with HF-PG (Figure B) CONCLUSION: A normal pregnancy is a protective factor against hyper- tension later in life in both obese and non-obese animals. 45 The impact of multiparity on peripartum and cardiovascular outcomes in women with repaired tetralogy of Fallot Torri Metz 1 , Samuel Hayes 2 , Clarisa Garcia 2 , Anji Yetman 2 1 University of Utah, Obstetrics and Gynecology, Salt Lake City, UT, 2 University of Utah, Pediatrics, Salt Lake City, UT OBJECTIVE: Little data exist on multiparity in women with repaired tetralogy of Fallot (ToF). An uncomplicated first pregnancy is often considered a good prognostic indicator for future pregnancies. We assessed the impact of number of pregnancies on peripartum and long-term cardiac outcomes in this group of patients. STUDY DESIGN: Obstetric and cardiac data on women cared for at a tertiary institution over a 10-year period were analyzed. Pre-, peri- and post-partum echocardiographic studies were reviewed. The rela- tionship between clinical variables and peripartum and cardiovascu- lar outcomes was sought. Multivariable logistic regression was used to assess the impact of multiparity on a composite long-term ad- verse outcome defined as death, heart failure, or unanticipated cardiac surgery. RESULTS: There were 94 pregnancies (median 3.0 [1-10]) in 32 women resulting in 79 live births. All women except 1 were NYHA class I at onset of pregnancy. Forty (38/94) percent of pregnancies occurred in women with an RV to pulmonary artery (PA) conduit in place. Pro- gressive valvar obstruction or insufficiency occurred in 23% & 55%, respectively. Cardiac complications occurred in 24 (25%) pregnancies including new onset heart failure (CHF) in 21, pulmonary emboli in 5, endocarditis in 1, and new arrhythmias in 9. Absence of complications with initial pregnancy did not correlate with risk with future pregnan- cies (r0.3, pNS). Obstetrical complications included preeclampsia in 6, gestational diabetes in 2 and PPROM in 2. Premature delivery occurred in 15 (19%), neonatal heart disease in 5 (6%), and perinatal death in 4 (5%). Long-term adverse outcome occurred in 15/32 (47%) women. Each subsequent delivery increased the odds of a composite adverse long-term outcome 4-fold despite adjustment for BMI and age at first pregnancy (OR 4.02, 95% CI 1.22,13.21). CONCLUSION: Women with repaired ToF often deliver preterm. Peri- partum CHF is common. Multiparity appears to increase the risk of long-term adverse cardiac outcomes. 46 The effect of prenatal pravastatin treatment on altered fetal programming of cardiovascular function in a preeclampsia-like murine model Mollie McDonnold 1 , Esther Tamayo 1 , Talar Kechichian 1 , Rheanna Urrabaz-Garza 1 , Monica Longo 1 , George Saade 1 , Maged Costantine 1 1 University of Texas Medical Branch, Obstetrics and Gynecology, Galveston, TX OBJECTIVE: Preeclampsia creates an adverse intrauterine environment which alters fetal programming and results in long term cardiovascu- lar dysfunction in the offspring. Pravastatin has been shown to pre- vent preeclampsia in animal models. Our aim was to evaluate the role of pravastatin on developmental programming of adult cardiovascu- lar function using a well characterized murine model. STUDY DESIGN: On day 8 of gestation, CD-1 mice were injected through the tail vein with Adv-sFlt-1 and randomly allocated to prav- astatin (5 mg/kg/day; sFlt-prav) or water (sFlt) until weaning. A con- trol group was injected with adenovirus carrying the murine immu- Figure SBP and DBP in age-matched nulligravid and primigravid mice exposed to A, standard fat or B, high fat diet. Oral Concurrent Session 4 www. AJOG.org Friday, February 15, 2013 • 1:15 pm – 3:30 pm • Continental 5 S28 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013

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Oral Concurrent Session 4 www.AJOG.orgFriday, February 15, 2013 • 1:15 pm – 3:30 pm • Continental 5

PHYSIOLOGY/GENETICS

Abstracts 44 – 52

Moderators: William Gilbert, MD; Jim Goldberg, MD

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44 The effect of pregnancy on long-term maternalardiovascular function in a mouse modelf pre-pregnancy obesity

Egle Bytautiene1, Esther Tamayo1, Huazhi Yin1,hyllis Gamble1, George Saade1

1University of Texas Medical Branch, Obstetrics andynecology, Galveston, TX

OBJECTIVE: The prevalence of pre-existing obesity in the pregnantopulation continues to increase. Obesity itself is associated with ad-erse cardiovascular outcomes later in life, and pregnancy may com-ound this risk. The objective of our study was to evaluate whetherregnancy increases the risk of cardiovascular abnormalities later in

ife beyond the risks associated with pre-pregnancy obesity, using aell characterized animal model.

STUDY DESIGN: Virgin CD-1 female mice were placed on standard (SF)r high fat (HF) diet. After 3 months, mice were randomly allocated tobreeding versus non breeding group resulting in 4 groups: primi-

ravid on SF (SF-PG) or HF (HF-PG) and nulligravid on SF (SF-NG)r HF (HF-NG). The primigravid group proceeded through a normalregnancy and delivery. After weaning of the primigravid group, allnimals were contemporaneously placed on SF diet. At 6 months postartum, PG mice were age-matched to NG mice and fitted with te-

emetric transducers for systolic (SBP) and diastolic blood (DBP)ressure recordings in the conscious, unrestrained animals. Student-test and Mann-Whitney test were used for statistical analysis (sig-ificance: p�0.05).

RESULTS: There were no differences in BP between nulligravid HF andF mice. The primigravid HF mice exposed to pregnancy had signif-cantly higher SBP (p�0.04) than SF-PG mice. Comparisons withiniet groups revealed that SF-NG had significantly higher SBPp�0.03) and DBP (p�0.04) than SF-PG mice (Figure A). HF-NGroup exhibited significantly higher DBP (p�0.03) and a trend to-ards higher SBP compared with HF-PG (Figure B)

CONCLUSION: A normal pregnancy is a protective factor against hyper-tension later in life in both obese and non-obese animals.

Figure

SBP and DBP in age-matched nulligravid and primigravid mice exposed toA, standard fat or B, high fat diet.

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S28 American Journal of Obstetrics & Gynecology Supplement to JANUARY 20

45 The impact of multiparity on peripartumnd cardiovascular outcomes in womenith repaired tetralogy of Fallot

Torri Metz1, Samuel Hayes2, Clarisa Garcia2, Anji Yetman2

1University of Utah, Obstetrics and Gynecology, Salt Lake City, UT,2University of Utah, Pediatrics, Salt Lake City, UTOBJECTIVE: Little data exist on multiparity in women with repairedetralogy of Fallot (ToF). An uncomplicated first pregnancy is oftenonsidered a good prognostic indicator for future pregnancies. Wessessed the impact of number of pregnancies on peripartum andong-term cardiac outcomes in this group of patients.

STUDY DESIGN: Obstetric and cardiac data on women cared for at aertiary institution over a 10-year period were analyzed. Pre-, peri-nd post-partum echocardiographic studies were reviewed. The rela-ionship between clinical variables and peripartum and cardiovascu-ar outcomes was sought. Multivariable logistic regression was usedo assess the impact of multiparity on a composite long-term ad-erse outcome defined as death, heart failure, or unanticipatedardiac surgery.

RESULTS: There were 94 pregnancies (median 3.0 [1-10]) in 32 womenesulting in 79 live births. All women except 1 were NYHA class I atnset of pregnancy. Forty (38/94) percent of pregnancies occurred inomen with an RV to pulmonary artery (PA) conduit in place. Pro-ressive valvar obstruction or insufficiency occurred in 23% & 55%,espectively. Cardiac complications occurred in 24 (25%) pregnanciesncluding new onset heart failure (CHF) in 21, pulmonary emboli in 5,ndocarditis in 1, and new arrhythmias in 9. Absence of complicationsith initial pregnancy did not correlate with risk with future pregnan-

ies (r�0.3, p�NS). Obstetrical complications included preeclampsian 6, gestational diabetes in 2 and PPROM in 2. Premature deliveryccurred in 15 (19%), neonatal heart disease in 5 (6%), and perinataleath in 4 (5%). Long-term adverse outcome occurred in 15/32 (47%)omen. Each subsequent delivery increased the odds of a composite

dverse long-term outcome 4-fold despite adjustment for BMI andge at first pregnancy (OR 4.02, 95% CI 1.22,13.21).

CONCLUSION: Women with repaired ToF often deliver preterm. Peri-partum CHF is common. Multiparity appears to increase the risk oflong-term adverse cardiac outcomes.

46 The effect of prenatal pravastatin treatment onltered fetal programming of cardiovascular function

n a preeclampsia-like murine modelMollie McDonnold1, Esther Tamayo1, Talar Kechichian1,

heanna Urrabaz-Garza1, Monica Longo1, George Saade1,aged Costantine1

1University of Texas Medical Branch, Obstetrics and Gynecology,alveston, TX

OBJECTIVE: Preeclampsia creates an adverse intrauterine environmenthich alters fetal programming and results in long term cardiovascu-

ar dysfunction in the offspring. Pravastatin has been shown to pre-ent preeclampsia in animal models. Our aim was to evaluate the rolef pravastatin on developmental programming of adult cardiovascu-

ar function using a well characterized murine model.STUDY DESIGN: On day 8 of gestation, CD-1 mice were injectedhrough the tail vein with Adv-sFlt-1 and randomly allocated to prav-statin (5 mg/kg/day; sFlt-prav) or water (sFlt) until weaning. A con-

rol group was injected with adenovirus carrying the murine immu-

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