- Email: [email protected]
216: Relationship of mean arterial pressure, uterine artery Doppler and placental vascular indices: placental response to abnormal maternal perfusion
Poster Session I
Clinical Obstetrics, Epidemiology, Fetus, Medical-Surgical Complications, Neonatology, Physiology/Endocrinology, Prematurity
214 Left ventricular Tachykinin 1 gene expression is increased in chronically anemic fetal sheep Juulia Junno4, Juha Räsänen3, Jennifer Farwell2, Roger Hohimer2, Olli Vuolteenaho1, Lowell Davis2, Sonnet Jonker2 1 University of Oulu, Physiology, Oulu, Finland, 2Oregon Health and Science University, Obstetrics and Gynecology, Portland, OR, 3Kuopio University Hospital, Obstetrics and Gynecology, Kuopio, Finland, 4Oulu University Hospital, Obstetrics and Gynecology, Oulu, Finland
OBJECTIVE: Chronically anemic fetuses increase cardiac output by 50%. Anemia-induced cardiac remodeling is associated with diminished isovolumic contraction velocity acceleration (IVCVacc) and isovolumic relaxation velocity deceleration (IVRVdec) in the left ventricle indicating reduced ventricular contractility and relaxation. We therefore sought to determine if there were changes in genes that affect ventricular function in chronically anemic fetuses. STUDY DESIGN: 7 fetal sheep with twin gestations had catheters placed surgically and 1 randomly selected twin was made anemic by daily isovolumic hemorrhage for 8 days. At 126 days gestation echocardiographic studies were performed under anesthesia and tissues from the right (RV) and left (LV) ventricles were obtained. Agilent’s 8x15K Sheep Gene Expression array with greater than 2 fold changes were selected for qRT-PCR. RESULTS: Hematocrit was reduced in anemic fetuses as compared to controls 13.1 (2.5) vs 34.9 (5.2)% means (SD) as well as oxygen content 2.3 (0.4) vs 8.4 (1.7) ml/dl. LV and RV IVCVacc and IVRVdec, and MRNA expression/18s are shown below. All the data are presented as means (SD).* p⬍0.05. CONCLUSION: Neither changes in -adrenergic receptor 1, phospholamban, nor troponin C account for the decrease in left ventricular contractility and relaxation in anemic fetuses. Increased Tachykinin 1 gene expression through substance P and neurokinin A may be important in mediating decreased ionotropy and lusitropy in chronic fetal anemia.
215 Maternal biomarkers of adiposity are associated with infant birthweight Kataneh Salari1, Anjel Vahratian2, Marjorie Treadwell1 1 University of Michigan Health System, Department of Obstetrics and Gynecology, Ann Arbor, MI, 2University of Michigan Health System, Department of Obstetrics and Gynecology, Ann Arbor, MI
OBJECTIVE: The purpose of this study is to evaluate the association between maternal biomarkers of adiposity and infant birthweight. STUDY DESIGN: Fifty patients in the first trimester of pregnancy receiving care through the University of Michigan Health System were recruited to participate into the study. Maternal morphometry (weight, height) was obtained at the first visit. Biomarkers related to maternal adiposity were drawn (glucose, insulin, adiponectin, leptin, LDL, HDL, total cholesterol, triglycerides, hemoglobin A1C) in each trimester. Maternal visceral fat indices (preperitoneal and subcutaneous fat measurements) were also measured in each trimester. Information regarding infant birthweight was obtained by reviewing patient records. RESULTS: Forty-five patients completed the study after initial enrollment. The average age of subjects enrolled was 30.4 years. The mean birthweight was 3429 g. Using linear regression analysis, positive determinants of birthweight were gestational age, maternal fasting glucose values in the third trimester, and maternal triglyceride levels in the first trimester. For every 10 mg/dL increase in maternal fasting
S100
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glucose level and triglyceride level, there was a 300 g (P ⫽ 0.005) and a 69 g (P ⫽ 0.008) increase in birthweight, respectively. Maternal adiponectin levels in the first and second trimester were negatively associated with birthweight. For every 1 ug/mL increase in maternal adiponectin level, there was a 33-37 g decrease in birthweight (P ⫽ 0.05). There was no association between birthweight and the remainder of maternal biomarkers of adiposity, morphometric measurements, or maternal visceral fat indices. CONCLUSION: Maternal glucose, triglycerides, and adiponectin levels were significantly associated with infant birthweight, consistent with results of a recently reported study of maternal biomarkers of adiposity in pregnancy. Thus, biomarkers that accurately reflect the maternal metabolic state may help better identify pregnant women at risk for fetal macrosomia.
216 Relationship of mean arterial pressure, uterine artery Doppler and placental vascular indices: placental response to abnormal maternal perfusion Katherine Goetzinger1, Alison Cahill1, Linda Odibo1, George Macones1, Anthony Odibo1 1 Washington University in St. Louis, Obstetrics and Gynecology, St. Louis, MO
OBJECTIVE: Maternal mean arterial pressure (MAP), uterine artery (UA) Doppler, and placental vascular indices have been proposed as first-trimester screening tools for pregnancies at high risk for preeclampsia (PEC); however, their relationship is unknown. We sought 1) to evaluate the relationship between first-trimester UA Doppler and measures of placental perfusion and 2) to determine if these measures are altered by MAP. STUDY DESIGN: This is a prospective cohort study of singleton gestations presenting at 11-14 weeks for aneuploidy screening. MAP was calculated at the initial visit. Placental vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were obtained with 4-D power Doppler images of the placenta using the VOCAL program. Mean UA pulsatility indices (PI) were calculated. Only pregnancies with normal outcomes were analyzed in order to establish a physiologic basis for any relationship. Placental vascular indices were compared between women with abnormal (⬍70 mmHg or ⬎110 mmHg) and normal MAP using Mann-Whitney U statistics. Pearson correlation coefficients were used to evaluate the association between UA PI and placental vascular indices. RESULTS: Of 599 patients, 36 (6.0%) had abnormal MAP. Both FI (47.7 vs 43.8, p⫽0.04) and VFI (9.3 vs 6.1, p⫽0.03) were significantly higher in women with low MAP compared to normal MAP; however, there was no significant difference in any of the placental vascular indices in women with high MAP compared to normal MAP (Table). There was no significant correlation between UA PI and any placental vascular index (VI: r⫽ ⫺0.05, p⫽0.22; FI: r⫽ ⫺0.07, p⫽0.07; VFI: r⫽ ⫺0.05, p⫽0.21). CONCLUSION: A compensatory increase in placental blood flow, reflected by increased vascular indices, in patients with low MAP suggests these two parameters are not independent; however, the lack of correlation between UA Doppler and placental vascular indices support their combined use as screening tools for PEC.
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013
www.AJOG.org
Clinical Obstetrics, Epidemiology, Fetus, Medical-Surgical Complications, Neonatology, Physiology/Endocrinology, Prematurity
Poster Session I
219 Profiling of microRNA by next-gen deep sequencing reveals novel and modifiable miRNA species in human breast milk Kjersti Aagaard1, Erika Munch1, R. Alan Harris3, Mahmoud Mohammad2, Ashley Benham6, Sasha Pejerrey4, Preethi Gunaratne5, Morey Haymond2 1 Baylor College of Medicine, Maternal-Fetal Medicine, Houston, TX, 2Baylor College of Medicine, Pediatrics, Houston, TX, 3Baylor College of Medicine, Molecular and Human Genetics, Bioinformatics Research Lab, Houston, TX, 4 Baylor College of Medicine, Molecular and Cell Biology, Houston, TX, 5 Baylor College of Medicine, Pathology, Houston, TX, 6University of Houston, Biology and Biochemistry, Houston, TX
*Data expressed as medians and interquartile ranges.
217 WITHDRAWN 218 Does fetal gender play a role in the detection of fetal microchimerism? Kimberly Ma1, J. Nelson2, V. Gadi3, Hilary Gammill1 1
University of Washington, Obstetrics and Gynecology, Seattle, WA, University of Washington, Rheumatology, Seattle, WA, 3University of Washington, Medical Oncology, Seattle, WA 2
OBJECTIVE: The protective association between parity and breast cancer appears to be stronger in women with sons compared to daughters. The underlying mechanism is unknown and has been hypothesized to be immunologic or endocrinologic. During pregnancy, transplacental cellular exchange results in microchimerism (Mc). Mc can persist and is associated with protection from breast cancer. We sought to evaluate whether fetal Mc concentration varies according to fetal gender, thereby potentially contributing to the differential protection of parity with sons versus daughters. STUDY DESIGN: Pregnant women and parous, nonpregnant women were studied. Blood samples were obtained, and DNA was extracted from Ficoll-purified peripheral blood mononuclear cells. Maternal and fetal HLA genotyping was conducted, and fetal Mc was quantified employing a panel of Q-PCR assays targeting fetal-specific HLA alleles. Detection of fetal Mc was compared according to fetal gender. Among the pregnant women, current fetal gender was used to define male versus female exposure. Prior birth of any male child was considered male exposure in nonpregnant, parous women. RESULTS: 97 subjects were studied, 35 during pregnancy and 62 outside of pregnancy. There were no differences in the detection of fetal Mc according to fetal gender. In pregnant women, 6.7% (1/15) of women with a male fetus had fetal Mc detected compared to 10.0% (2/20) with a female fetus (p⫽0.73). Outside of pregnancy, fetal Mc was detected in 18.9% (7/37) of those with a history of a male fetus compared to 20.0% (5/25) of those with only a female fetus (p⫽0.92). CONCLUSION: We observed no association of fetal gender with detection rates of fetal Mc during pregnancy or in parous women. It is possible that fetal Mc may contribute to known epidemiological findings of differential protection of parity for diseases according to offspring gender. However, our findings suggest that if this is the case, functional, rather than quantitative differences in Mc by fetal gender are more likely to underlie a relationship.
OBJECTIVE: While breast milk has unique health advantages for infants, the mechanisms by which it regulates the physiology of newborns are incompletely understood. microRNAs (miRNAs), a class of noncoding RNAs, are criticaltranscellularmediatorsofposttranscriptionalgeneregulation.Wehypothesized that breast milk in general, and milk fat globules in particular, contain significant numbers of known and limited novel miRNA species detectable with massively parallel sequencing. STUDY DESIGN: Extracted RNA from 3 well-characterized cohorts of lactating women (before and after rhGH, high glucose vs galactose diet modified, or high fat vs high carbohydrate diet modified; Figure panel A) was smRNA-enriched. smRNA was subjected to massively parallel shotgun sequencing, and robustly analyzed on customized pipelines to identify functional targets. Data were validated with qPCR. RESULTS: smRNA-Seq was performed to generate 124,110,646 36-nt reads, including 308 of 1018 (29%) known mature miRNAs (miRBase 16.0). We identified 21 putative novel miRNAs, of which 12 were validated. Collectively, these miRNAs target 9074 genes; the 10 most abundant of these predicted to target 2691 genes with enrichment for transcriptional regulation of metabolic and immune responses (panels B&C). Moreover, expression of several novel miRNAs were significantly and specifically altered following maternal high-fat diet modifications (p⬍0.05). CONCLUSION: We have shown for the first time that novel (and known) miRNAs are enriched in breast milk, and expression of several novel miRNA species is regulated by a high fat maternal diet. Based on robust pathway mapping, our data supports the notion that these maternally secreted miRNAs-which are stable in the milk fat globulesplay a regulatory role in the infant and account in part for the health benefits of breast milk. We speculate that regulation of these miRNA by a high fat maternal diet enables modulation of fetal metabolism to accommodate significant dietary challenges.
Identification and functional analysis of novel miRNA in human breast milk
Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
S101
Clinical Obstetrics, Epidemiology, Fetus, Medical-Surgical Complications, Neonatology, Physiology/Endocrinology, Prematurity
214 Left ventricular Tachykinin 1 gene expression is increased in chronically anemic fetal sheep Juulia Junno4, Juha Räsänen3, Jennifer Farwell2, Roger Hohimer2, Olli Vuolteenaho1, Lowell Davis2, Sonnet Jonker2 1 University of Oulu, Physiology, Oulu, Finland, 2Oregon Health and Science University, Obstetrics and Gynecology, Portland, OR, 3Kuopio University Hospital, Obstetrics and Gynecology, Kuopio, Finland, 4Oulu University Hospital, Obstetrics and Gynecology, Oulu, Finland
OBJECTIVE: Chronically anemic fetuses increase cardiac output by 50%. Anemia-induced cardiac remodeling is associated with diminished isovolumic contraction velocity acceleration (IVCVacc) and isovolumic relaxation velocity deceleration (IVRVdec) in the left ventricle indicating reduced ventricular contractility and relaxation. We therefore sought to determine if there were changes in genes that affect ventricular function in chronically anemic fetuses. STUDY DESIGN: 7 fetal sheep with twin gestations had catheters placed surgically and 1 randomly selected twin was made anemic by daily isovolumic hemorrhage for 8 days. At 126 days gestation echocardiographic studies were performed under anesthesia and tissues from the right (RV) and left (LV) ventricles were obtained. Agilent’s 8x15K Sheep Gene Expression array with greater than 2 fold changes were selected for qRT-PCR. RESULTS: Hematocrit was reduced in anemic fetuses as compared to controls 13.1 (2.5) vs 34.9 (5.2)% means (SD) as well as oxygen content 2.3 (0.4) vs 8.4 (1.7) ml/dl. LV and RV IVCVacc and IVRVdec, and MRNA expression/18s are shown below. All the data are presented as means (SD).* p⬍0.05. CONCLUSION: Neither changes in -adrenergic receptor 1, phospholamban, nor troponin C account for the decrease in left ventricular contractility and relaxation in anemic fetuses. Increased Tachykinin 1 gene expression through substance P and neurokinin A may be important in mediating decreased ionotropy and lusitropy in chronic fetal anemia.
215 Maternal biomarkers of adiposity are associated with infant birthweight Kataneh Salari1, Anjel Vahratian2, Marjorie Treadwell1 1 University of Michigan Health System, Department of Obstetrics and Gynecology, Ann Arbor, MI, 2University of Michigan Health System, Department of Obstetrics and Gynecology, Ann Arbor, MI
OBJECTIVE: The purpose of this study is to evaluate the association between maternal biomarkers of adiposity and infant birthweight. STUDY DESIGN: Fifty patients in the first trimester of pregnancy receiving care through the University of Michigan Health System were recruited to participate into the study. Maternal morphometry (weight, height) was obtained at the first visit. Biomarkers related to maternal adiposity were drawn (glucose, insulin, adiponectin, leptin, LDL, HDL, total cholesterol, triglycerides, hemoglobin A1C) in each trimester. Maternal visceral fat indices (preperitoneal and subcutaneous fat measurements) were also measured in each trimester. Information regarding infant birthweight was obtained by reviewing patient records. RESULTS: Forty-five patients completed the study after initial enrollment. The average age of subjects enrolled was 30.4 years. The mean birthweight was 3429 g. Using linear regression analysis, positive determinants of birthweight were gestational age, maternal fasting glucose values in the third trimester, and maternal triglyceride levels in the first trimester. For every 10 mg/dL increase in maternal fasting
S100
www.AJOG.org
glucose level and triglyceride level, there was a 300 g (P ⫽ 0.005) and a 69 g (P ⫽ 0.008) increase in birthweight, respectively. Maternal adiponectin levels in the first and second trimester were negatively associated with birthweight. For every 1 ug/mL increase in maternal adiponectin level, there was a 33-37 g decrease in birthweight (P ⫽ 0.05). There was no association between birthweight and the remainder of maternal biomarkers of adiposity, morphometric measurements, or maternal visceral fat indices. CONCLUSION: Maternal glucose, triglycerides, and adiponectin levels were significantly associated with infant birthweight, consistent with results of a recently reported study of maternal biomarkers of adiposity in pregnancy. Thus, biomarkers that accurately reflect the maternal metabolic state may help better identify pregnant women at risk for fetal macrosomia.
216 Relationship of mean arterial pressure, uterine artery Doppler and placental vascular indices: placental response to abnormal maternal perfusion Katherine Goetzinger1, Alison Cahill1, Linda Odibo1, George Macones1, Anthony Odibo1 1 Washington University in St. Louis, Obstetrics and Gynecology, St. Louis, MO
OBJECTIVE: Maternal mean arterial pressure (MAP), uterine artery (UA) Doppler, and placental vascular indices have been proposed as first-trimester screening tools for pregnancies at high risk for preeclampsia (PEC); however, their relationship is unknown. We sought 1) to evaluate the relationship between first-trimester UA Doppler and measures of placental perfusion and 2) to determine if these measures are altered by MAP. STUDY DESIGN: This is a prospective cohort study of singleton gestations presenting at 11-14 weeks for aneuploidy screening. MAP was calculated at the initial visit. Placental vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were obtained with 4-D power Doppler images of the placenta using the VOCAL program. Mean UA pulsatility indices (PI) were calculated. Only pregnancies with normal outcomes were analyzed in order to establish a physiologic basis for any relationship. Placental vascular indices were compared between women with abnormal (⬍70 mmHg or ⬎110 mmHg) and normal MAP using Mann-Whitney U statistics. Pearson correlation coefficients were used to evaluate the association between UA PI and placental vascular indices. RESULTS: Of 599 patients, 36 (6.0%) had abnormal MAP. Both FI (47.7 vs 43.8, p⫽0.04) and VFI (9.3 vs 6.1, p⫽0.03) were significantly higher in women with low MAP compared to normal MAP; however, there was no significant difference in any of the placental vascular indices in women with high MAP compared to normal MAP (Table). There was no significant correlation between UA PI and any placental vascular index (VI: r⫽ ⫺0.05, p⫽0.22; FI: r⫽ ⫺0.07, p⫽0.07; VFI: r⫽ ⫺0.05, p⫽0.21). CONCLUSION: A compensatory increase in placental blood flow, reflected by increased vascular indices, in patients with low MAP suggests these two parameters are not independent; however, the lack of correlation between UA Doppler and placental vascular indices support their combined use as screening tools for PEC.
American Journal of Obstetrics & Gynecology Supplement to JANUARY 2013
www.AJOG.org
Clinical Obstetrics, Epidemiology, Fetus, Medical-Surgical Complications, Neonatology, Physiology/Endocrinology, Prematurity
Poster Session I
219 Profiling of microRNA by next-gen deep sequencing reveals novel and modifiable miRNA species in human breast milk Kjersti Aagaard1, Erika Munch1, R. Alan Harris3, Mahmoud Mohammad2, Ashley Benham6, Sasha Pejerrey4, Preethi Gunaratne5, Morey Haymond2 1 Baylor College of Medicine, Maternal-Fetal Medicine, Houston, TX, 2Baylor College of Medicine, Pediatrics, Houston, TX, 3Baylor College of Medicine, Molecular and Human Genetics, Bioinformatics Research Lab, Houston, TX, 4 Baylor College of Medicine, Molecular and Cell Biology, Houston, TX, 5 Baylor College of Medicine, Pathology, Houston, TX, 6University of Houston, Biology and Biochemistry, Houston, TX
*Data expressed as medians and interquartile ranges.
217 WITHDRAWN 218 Does fetal gender play a role in the detection of fetal microchimerism? Kimberly Ma1, J. Nelson2, V. Gadi3, Hilary Gammill1 1
University of Washington, Obstetrics and Gynecology, Seattle, WA, University of Washington, Rheumatology, Seattle, WA, 3University of Washington, Medical Oncology, Seattle, WA 2
OBJECTIVE: The protective association between parity and breast cancer appears to be stronger in women with sons compared to daughters. The underlying mechanism is unknown and has been hypothesized to be immunologic or endocrinologic. During pregnancy, transplacental cellular exchange results in microchimerism (Mc). Mc can persist and is associated with protection from breast cancer. We sought to evaluate whether fetal Mc concentration varies according to fetal gender, thereby potentially contributing to the differential protection of parity with sons versus daughters. STUDY DESIGN: Pregnant women and parous, nonpregnant women were studied. Blood samples were obtained, and DNA was extracted from Ficoll-purified peripheral blood mononuclear cells. Maternal and fetal HLA genotyping was conducted, and fetal Mc was quantified employing a panel of Q-PCR assays targeting fetal-specific HLA alleles. Detection of fetal Mc was compared according to fetal gender. Among the pregnant women, current fetal gender was used to define male versus female exposure. Prior birth of any male child was considered male exposure in nonpregnant, parous women. RESULTS: 97 subjects were studied, 35 during pregnancy and 62 outside of pregnancy. There were no differences in the detection of fetal Mc according to fetal gender. In pregnant women, 6.7% (1/15) of women with a male fetus had fetal Mc detected compared to 10.0% (2/20) with a female fetus (p⫽0.73). Outside of pregnancy, fetal Mc was detected in 18.9% (7/37) of those with a history of a male fetus compared to 20.0% (5/25) of those with only a female fetus (p⫽0.92). CONCLUSION: We observed no association of fetal gender with detection rates of fetal Mc during pregnancy or in parous women. It is possible that fetal Mc may contribute to known epidemiological findings of differential protection of parity for diseases according to offspring gender. However, our findings suggest that if this is the case, functional, rather than quantitative differences in Mc by fetal gender are more likely to underlie a relationship.
OBJECTIVE: While breast milk has unique health advantages for infants, the mechanisms by which it regulates the physiology of newborns are incompletely understood. microRNAs (miRNAs), a class of noncoding RNAs, are criticaltranscellularmediatorsofposttranscriptionalgeneregulation.Wehypothesized that breast milk in general, and milk fat globules in particular, contain significant numbers of known and limited novel miRNA species detectable with massively parallel sequencing. STUDY DESIGN: Extracted RNA from 3 well-characterized cohorts of lactating women (before and after rhGH, high glucose vs galactose diet modified, or high fat vs high carbohydrate diet modified; Figure panel A) was smRNA-enriched. smRNA was subjected to massively parallel shotgun sequencing, and robustly analyzed on customized pipelines to identify functional targets. Data were validated with qPCR. RESULTS: smRNA-Seq was performed to generate 124,110,646 36-nt reads, including 308 of 1018 (29%) known mature miRNAs (miRBase 16.0). We identified 21 putative novel miRNAs, of which 12 were validated. Collectively, these miRNAs target 9074 genes; the 10 most abundant of these predicted to target 2691 genes with enrichment for transcriptional regulation of metabolic and immune responses (panels B&C). Moreover, expression of several novel miRNAs were significantly and specifically altered following maternal high-fat diet modifications (p⬍0.05). CONCLUSION: We have shown for the first time that novel (and known) miRNAs are enriched in breast milk, and expression of several novel miRNA species is regulated by a high fat maternal diet. Based on robust pathway mapping, our data supports the notion that these maternally secreted miRNAs-which are stable in the milk fat globulesplay a regulatory role in the infant and account in part for the health benefits of breast milk. We speculate that regulation of these miRNA by a high fat maternal diet enables modulation of fetal metabolism to accommodate significant dietary challenges.
Identification and functional analysis of novel miRNA in human breast milk
Supplement to JANUARY 2013 American Journal of Obstetrics & Gynecology
S101