197: Maternal race and gestational age dependent changes in maternal serum lipids

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Clinical Obstetrics, Epidemiology, Fetus, Medical-Surgical Complications, Neonatology, Physiology/Endocrinology, Prematurity

195 Critical enzymes for endocannabinoid metabolism in a baboon model of maternal obesity Brian Brocato1, Zorica Janjetovich2, Andrzej Slominski2, Mari Giancarlo1, Gene Hubbard3, Edward Dick4 1 University of TN Health Science Center, Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Memphis, TN, 2University of TN Health Science Center, Pathology, Memphis, TN, 3University of Texas Health Science Center at San Antonio, Pathology, San Antonio, TX, 4Texas Biomedical Research Institute, Pathology, San Antonio, TX

OBJECTIVE: Maternal obesity is a risk factor for adverse fetal outcomes including fetal loss and abnormal growth. It has been suggested that the increase in endocannabinoid (ECB) system tone found in obesity may cause early fetal loss. We hypothesized that expression of ECB degrading enzymes (FAAH, MAGL and DAGL) will be altered in placentas of obese baboons. STUDY DESIGN: Four obese and four non-obese baboons (Papio spp) were studied as previously described. Placenta was retrieved during C-section and was flash- frozen and stored at ⫺80°. RNA was isolated using Trizol. 5 ␮g RNA was used for cDNA synthesis (Roche, Basel Switzerland). Primate specific primers and TagMan probes (Roche Universal probes library) were used for Real-time PCR performed on a Roche Light Cycler 480. The amounts were compared to a reference gene (␤- actin) using a comparative CT method. All reactions were performed in triplicate with the appropriate controls. Relative gene expression data were calculated using ⌬Ct method. Data are expressed as mean ⫾ SEM. Two-tailed t-Student test was used to compare the variables; p⬍0.05 was considered significant. RESULTS: There were no differences in the relative expression of gene transcripts between obese and non-obese animals. The expression of FAAH was 0.55 ⫾0.1 in obese (Ob) vs. 0.76 ⫾0.2 in non-obese (nOb) animals, DAGL 0.69 ⫾0.2 (Ob) vs. 0.75⫾0.04 (nOb) and MAGL 5.9 ⫾0.9 (Ob) vs. 5.62⫾0.4 (nOb). CONCLUSION: This is the first report regarding the expression of ECB enzyme gene transcripts in term non-human primate placentas. The detected 38% decrease in FAAH expression seen in the placenta of obese baboons was not statistically significant. Further studies are necessary to determine whether placental ECB metabolizing enzymes might serve as a potential target for intervention to possibly improve poor fetal outcomes associated with maternal obesity.

Poster Session I

to lean women (Figure). There was no significant difference in serum free IGF-II median levels between obese (25.3 [17.9-41.1] ng/mL) and lean (34.4 [26.6-62.0] ng/mL) women. There was no significant up- or down-regulation of placental Igf1r (FC 1.21, p ⫽ .15) or Igf2r (FC 1.04, p ⫽ .58) expression among obese women. CONCLUSION: Serum free IGF-I levels are decreased in obese women during the first trimester. This may be a result of an obesity-induced insulin resistance blunting effect on IGF-binding protein levels. Further analysis of the IGF-axis is required to clarify this finding, which includes determination of serum levels of total IGF, IGF-binding proteins, and PAPP-A.

197 Maternal race and gestational age dependent changes in maternal serum lipids Christina Scifres1, Janet Catov1, Hygriv Simhan1 1 University of Pittsburgh, Department of Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh, PA

196 The insulin-like growth factor axis in healthy obese and lean women in the first trimester Carlton Schwab1, Mark Alanis2 1 Medical University of South Carolina, Obstetrics and Gynecology, Charleston, SC, 2Colorado Springs Memorial Hospital, Maternal-Fetal Medicine, Colorado Springs, CO

OBJECTIVE: To examine serum free IGF-I and IGF-II levels and transcript levels for placental IGF receptors (Igf1r and Igf2r transcripts) in obese and lean women in the first trimester. STUDY DESIGN: Serum and placental specimens were collected at the time of voluntary termination of pregnancy in obese (BMI ⱖ 30) and lean (BMI 18.5-24.9) subjects between 8 0/7 and 13 6/7 weeks of gestation. Subjects were matched 1:1 by race/ethnicity, smoking status, and gestational age. Serum was analyzed by ELISA for free IGF-I and IGF-II, and RNA was extracted from placental samples to measure Igf1r and Igf2r transcript levels by RT-qPCR. Serum IGF levels were log transformed to induce normality. Student’s t-tests were performed on normally distributed data to compare differences in means. Skewed data were analyzed by the Wilcoxon rank sum test. Fold-changes in Igf1r and Igf2r were calculated by the delta-delta Cq calculation. Two-tailed p values ⬍ 0.05 were considered statistically significant. A sample size calculation (n ⫽ 25 matched pairs) was performed to provide ⬎ 80% power to detect a relative 25% difference in serum IGF-I levels between groups. RESULTS: Fifty-four women (27 matched pairs) were enrolled consecutively. There were no differences in age, parity, or other demographic variables. Serum free IGF-I was significantly lower in obese compared

OBJECTIVE: Maternal adaptation to pregnancy involves alterations in serum lipids, and aberrations have been linked to adverse pregnancy outcomes with significant race disparities. We considered that maternal serum lipids in the 1st and 2nd trimesters would vary by maternal race. STUDY DESIGN: 185 women who had maternal serum cholesterol, HDL, LDL, and triglycerides measured at less than 13 weeks and between 24-28 weeks’ gestation were included in this analysis. Individual species of fatty acids were also measured at both time points in a subset of 127 women. We analyzed differences in maternal serum lipids between black and white women using univariable and multivariable methods. RESULTS: Maternal serum lipids were measured in 76 (41%) white women and 109 (59%) black women. After adjustment, maternal serum triglycerides were lower in black women at less than 13 weeks (⫺13.1 mg/dL, 95% CI ⫺25.7,⫺0.45, p⫽0.04) and between 24-28 weeks’ gestation (⫺41.6 mg/dL, 95% CI ⫺57.6, ⫺25.6, p⬍0.01) compared to white women. Total fatty acids were also lower in black women at less than 13 weeks (⫺28.9 mg/dL, 95% CI ⫺48.6, ⫺9.1, p⬍0.01) and at 24-28 weeks (⫺54.9 mg/dL, 95% CI ⫺82.4,27.2, p⬍0.01). In addition, black women had lower levels of saturated, monounsaturated, and polyunsaturated fatty acid levels at both time points and higher levels of omega 6 fatty acids at 24-28 weeks’ compared to white women. HDL levels were higher in black women at less than 13 weeks (3.8 mg/dL, 95% CI 0.5-7.1, p⬍0.03) and at 24-28 weeks’ gestation (7.7 mg/dL, 95% CI 2.7-12.8, p⬍0.01).

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Poster Session I

Clinical Obstetrics, Epidemiology, Fetus, Medical-Surgical Complications, Neonatology, Physiology/Endocrinology, Prematurity

CONCLUSION: Black women had lower levels of triglycerides and fatty

acids in the 1st and 2nd trimesters compared to white women, and black women had higher levels of omega-6 fatty acids at 24-28 weeks. Triglycerides and fatty acids are essential for fetal growth and development, and higher levels of omega-6 fatty acids have been linked to preterm birth. Further investigation is necessary to determine whether these lipid differences contribute to race disparities in pregnancy outcomes.

198 Prolactin derived vasoinhibins are associated with inflammation in mid-gestation Christy Pearce1, Linah Al-Alem2, John O’Brien2, Kristine Lain3, Wendy Hansen2, Thomas Curry2 1

Vanderbilt University, OB/GYN, Nashville, TN, 2University of Kentucky, OB/GYN, Lexington, KY, 3Norton Healthcare, Maternal Fetal Medicine, Louisville, KY

OBJECTIVE: Prolactin derived vasoinhibins have been implicated in the pathophysiology of preeclampsia and peripartum cardiomyopathy via a pro-inflammatory mechanism. We sought to determine the presence and examine the relationship of these prolactin derived vasoinhibins and inflammation in mid-gestation. STUDY DESIGN: Women with a singleton gestation between 16-23 weeks without exclusion for preexisting medical conditions were recruited as the study cohort. Women with preeclampsia at 24-42 weeks were recruited as physiologic standards. Serum was tested for C-reactive protein with a turbidimetric assay, prolactin with an immunoassay, and prolactin derived vasoinhibins via immunoprecipitation and Western blot. A sample by which to normalize vasoinhibin expression across different Western blots was selected from one of the recruited preeclamptic standards. Statistical analysis included t-test and correlation coefficients. RESULTS: Sixty subjects were recruited at an average of 19.9 ⫾ 1.5 weeks gestation for the study cohort. The mean age was 22.4 ⫾ 3.6 years and mean body mass index (BMI) was 27.9 ⫾ 7.1 kg/m2. Most women were primigravidas (n⫽47, 78.3%) and Caucasian (n⫽43, 71.7%). Forty-nine (81.7%) of samples expressed a significant measurable optical density of PRL fragment on Western blot. Increasing prolactin derived vasoinhibins and the ratio of vasoinhibins to prolactin was associated with increasing C-reactive protein (rho⫽0.3, p⫽0.04 and rho⫽0.3, p⫽0.04). See figure 1. Significant differences in mean C-reactive protein were noted between samples above and below the median prolactin derived vasoinhibin optical density (9.7⫾8.1 vs. 6.3⫾6.1, p⫽0.03) and the median ratio of vasoinhibins to prolactin (9.9⫾8.1 vs. 6.2⫾6.1, p⫽0.02). CONCLUSION: Prolactin derived vasoinhibins are associated with inflammation in mid-gestation. Further examination of these prolactin fragments in larger, high risk cohorts may be instructive in the pathophysiology of obstetrical conditions.

Correlation of CRP with prolactin derived vasoinhibin and ratio of prolactin derived vasoinhibin to prolactin

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199 Maternal obesity suppresses placental fatty acid uptake in male offspring Elizabeth Brass1, Kent Thornburg2, Perrie O’Tierney2 1 Oregon Health & Science University, Obstetrics & Gynecology, Portland, OR, 2Oregon Health & Science University, Heart Research Center, Dept Cardiovascular Medicine, Portland, OR

OBJECTIVE: The fetus is dependent on the placenta for its supply of long chain polyunsaturated fatty acids (LCPUFA), which are essential in fetal growth and development. Previous work suggests that maternal body mass index is associated with fetal LCPUFA delivery and that males have greater fatty acid requirements than females during development. We hypothesized that male placental fatty acid uptake would be more sensitive to maternal BMI compared to females. STUDY DESIGN: Women were recruited upon admission to Labor & Delivery for cesarean section (n⫽25). At delivery, placental samples were collected for fatty acid uptake studies using 14C-labeled oleic acid (OA), arachidonic acid, (AA) and docosahexanoic acid (DHA) in placental explants. Uptake was calculated as nmol fatty acid/mg protein at 15 minutes. Results were stratified by fetal sex and maternal first trimester BMI (normal BMI⬍25, obese BMI⬎26). Women with significant co-morbidities were excluded. Dichotomous outcomes were analyzed using 1 way ANOVA followed by Tukey post-hoc testing; p⬍0.05 was used to indicate statistical significance. RESULTS: Placental fatty acid uptake of OA and AA in males of obese women was decreased 62% and 60% respectively compared to normal BMI women (p⬍0.001). In females, placental fatty acid uptake was not suppressed in the setting of obesity; OA and AA uptake in normal BMI women was reduced 49% and 48% respectively compared to its male cohort (p⬍0.01). There was no difference in DHA uptake between sex or BMI groups. Fatty acid transporter CD36 and binding protein FABP5 gene expression levels in males mirrored the fatty acid uptake suppression seen in obesity. CONCLUSION: Placentas from males with obese mothers had suppressed uptake of unsaturated fatty acids and expression of their transporters, while uptake in females was unaffected by maternal BMI. This data suggest that males born to high BMI mothers may have inadequate LCPUFA acquisition. Males may pay a higher developmental price in the setting of maternal obesity.

200 Fetoplacental endothelium demonstrate unique responses to physiologic hypoxemia Emily Su1, Hong Xin1, Chunfa Jie2, Nadareh Jafari3, Matthew Dyson1, Serdar Bulun1 1 Northwestern University Feinberg School of Medicine, Obstetrics and Gynecology, Chicago, IL, 2Northwestern University Feinberg School of Medicine, Surgery/Organ Transplantation, Chicago, IL, 3Northwestern University Feinberg School of Medicine, Center for Genetic Medicine, Chicago, IL

OBJECTIVE: Although physiologic, fetoplacental pO2 is relatively hypoxemic in comparison to postnatal life, ranging from 12-50 mm Hg (1.5 - 8% O2). In adults, hypoxic conditions have profound effects on endothelial cell function that are often deleterious. We sought to de-

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American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013