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Assessment of Cardiac Parameters in Large for Gestational Age Infants in Mothers with &without Gestational Diabetes: Correlation with Placental Pathology
Abstracts / Placenta 34 (2013) A1–A99
2. To examine the correlation between placental pathology findings and cardiac parameters in LGA infants. 3. To find correlations between maternal risk factors and cardiac parameters in LGA infants.
P1.128. PLACENTAL STOX1 Y153H MUTATION IS ASSOCIATED WITH SEVERE EARLY ONSET PREECLAMPSIA AND LOW BIRTH WEIGHT Caroline Dunk 1, Marie Van Djik 2, Laura Anderson 1, Cees Oudejans 2, Stephen J. Lye 1, 3 1
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; 2 Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands; 3 Departments of Obstetrics and Gynecology and Physiology, The University of Toronto, Toronto, ON, Canada Objective: Controversy exists over the strength of the association of the gain-of-function mutation of the STOX1 transcription factor (Y153H allele) with Preeclampsia (PE). The use of maternal blood may not be appropriate for genotyping studies as this gene is paternally imprinted leading to the maternal allele specific expression of STOX1 in the placenta; thus we hypothesise that placenta genotype is more informative. We have previously shown that the HH STOX placental genotype induces an EVT specific reduction in invasion through the upregulation of a-T catenin supporting our contention of a role for STOX1 in the pathogenesis of PE. Methods: Placental DNA was extracted from a cohort of Severe early onset PE with an AGA baby (n¼15), Severe early onset PE with IUGR (n¼17), Late Onset PE with an AGA baby (n¼11) and Term controls (n¼15). Sequencing of the STOX1 PCR product was performed by ACGT Inc. Toronto. Statistical analyses were performed using R software. Results: Assessment of the Y153H genotypes revealed that there was a 3.58 fold increased risk of severe early onset PE cases both with and without IUGR in comparison to term if the placenta was STOX1 HH. The placental samples from pregnancies with late onset of PE did not show this genotype correlation and resembled the term controls. When a preterm control group matched for gestational age with the severe early onset PE cases was also included in the analysis there was a highly significant association of the STOX1HH genotype with low birth weight, (p<0.002, corrected for ethnicity, fetal sex and PE). A further cohort of 250 PE and 250 control maternal and fetal samples are currently under analysis. Conclusions: These data support our hypothesis that defective EVT invasion associated with increased STOX1 transactivation is a precipitating factor in the development of PE. Funding: This work was funded by the CIHR MOP82811 http://dx.doi.org/10.1016/j.placenta.2013.06.164
P1.129. ASSESSMENT OF CARDIAC PARAMETERS IN LARGE FOR GESTATIONAL AGE INFANTS IN MOTHERS WITH &WITHOUT GESTATIONAL DIABETES: CORRELATION WITH PLACENTAL PATHOLOGY P. Charlagorla, H. Inany, M. Gudavalli, M. Chhabra, C. Salafia, B. Dygulska, P. Narula, A. Gad New York Methodist Hospital, Brooklyn/NY, USA Introduction: Large for gestational age (LGA) is defined as birth weight above the 90-th percentile for that gestational age. Maternal pre and gestational diabetes (GDM) and obesity are major risk factors leading to LGA babies. Perinatal hyperglycemia is thought to be the teratogen or causative agent, leading to major fetal complications, stillbirth, increased C-Sections and health care costs. Incidence of asymmetric septal hypertrophy (ASH) is of 31-38% in LGA newborns of GDM mothers, and 7% in nongestational diabetic mothers (NGDM). To this date, no study has distinguished and compared ASH findings in LGA newborns born to GDM/ NGDM mothers in comparison with placental pathology findings. Objectives: 1. Identify differences in placental pathology between GDM and NGDM mothers of LGA infants.
A55
Methodology: This is a retrospective study. Study subjects were LGA babies term newborns (GA 37- 40weeks) born to mothers with GDM (n¼31) and NGDM (n¼36). All babies were matched in terms of gestational age (GA) and mode of delivery and gender and underwent cardiac echocardiography (Echo) in the hospital before discharge as a part of routine care. Placental pathology reports are analyzed for placental parameters. Statistical analysis of categorical variables was carried out using chi-square and Fisher's exact tests as appropriate. Comparison of means was carried out using Student's t-test. A Pearson's correlation coefficient (r) calculation and multiple regression analysis performed on significant findings. Results: There are no significant differences between the 2 groups of LGA newborns. However, Body mass Index (BMI) was found to be higher in mothers with GDM. Placental thickness (not dimensions) was significantly increased in the GDM group but had no association to cardiac structural paramters. Correlating maternal BMI with different cardiac parameters in all LGA subjects showed a semi linear relationship with cardiac septal thickness (ST) (p¼0.03, (95%CI, 1.8-44). There was no relationship between maternal BMI and other cardiac parameters. Cardiac ST correlation with placental basal myofibers (p¼0.031) did not persist after controlling for other cardiac findings in regression analysis. Conclusion: 1. High maternal BMI is a major risk factor for GDM and ASH in the newborn. 2. Thick placenta could represent a marker for abnormal glucose metabolism during pregnancy. 3. Placental pathology exam has become to play a pivotal role in identifying newborns at risk for GDM related cardiac disease and opens the door for early interference. 4. Comparing the study findings to normal newborns in ongoing. http://dx.doi.org/10.1016/j.placenta.2013.06.165
P1.130. DEVELOPMENT OF ONLINE TEACHING MODULES FOR UNDERSTANDING PLACENTA PATHOLOGY David Grynspan 1, Benoit Desrochers 1, Andree Gruslin 2, 3, Laura McDonell 1, Julien Yockell-Lelievre 2, Christopher Ball 3, Nasser Al-Abbad 2, 3 1
Childrens Hospital of Eastern Ontario, Ontario, Canada; 2 The Ottawa Hospital, Ontario, Canada; 3 The University of Ottawa, Ontario, Canada
Introduction: A major trend in modern education has been the use of online instructional modules. The most notable example is the success of the Khan Academy, an online educational website which has several million viewers. These video modules are often made available free on video or file exchange sites such as youtube. The openness of these forums allows for rapid knowledge translation through the wide dissemination and global exchange of academic tutorials. A drawback is that the lack of confidentiality or control precludes use of direct clinical material. Thus abstract or conceptual fields such as mathematics, which can be taught using simple graphics, drawing and voice, are most amenable to online micro-tutorials as shown by the Khan Academy experience. Aim: The ability to map two-dimensional histological sections of placenta to the three dimensional structure is challenging due to the complexity of the branching structures and the numerous reflecting surfaces. We speculate that the education of pathology and obstetric trainees in this area would benefit from online instructional modules modeled after the Khan Academy tutorials since it is both an abstract and a visualization problem.
2. To examine the correlation between placental pathology findings and cardiac parameters in LGA infants. 3. To find correlations between maternal risk factors and cardiac parameters in LGA infants.
P1.128. PLACENTAL STOX1 Y153H MUTATION IS ASSOCIATED WITH SEVERE EARLY ONSET PREECLAMPSIA AND LOW BIRTH WEIGHT Caroline Dunk 1, Marie Van Djik 2, Laura Anderson 1, Cees Oudejans 2, Stephen J. Lye 1, 3 1
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; 2 Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands; 3 Departments of Obstetrics and Gynecology and Physiology, The University of Toronto, Toronto, ON, Canada Objective: Controversy exists over the strength of the association of the gain-of-function mutation of the STOX1 transcription factor (Y153H allele) with Preeclampsia (PE). The use of maternal blood may not be appropriate for genotyping studies as this gene is paternally imprinted leading to the maternal allele specific expression of STOX1 in the placenta; thus we hypothesise that placenta genotype is more informative. We have previously shown that the HH STOX placental genotype induces an EVT specific reduction in invasion through the upregulation of a-T catenin supporting our contention of a role for STOX1 in the pathogenesis of PE. Methods: Placental DNA was extracted from a cohort of Severe early onset PE with an AGA baby (n¼15), Severe early onset PE with IUGR (n¼17), Late Onset PE with an AGA baby (n¼11) and Term controls (n¼15). Sequencing of the STOX1 PCR product was performed by ACGT Inc. Toronto. Statistical analyses were performed using R software. Results: Assessment of the Y153H genotypes revealed that there was a 3.58 fold increased risk of severe early onset PE cases both with and without IUGR in comparison to term if the placenta was STOX1 HH. The placental samples from pregnancies with late onset of PE did not show this genotype correlation and resembled the term controls. When a preterm control group matched for gestational age with the severe early onset PE cases was also included in the analysis there was a highly significant association of the STOX1HH genotype with low birth weight, (p<0.002, corrected for ethnicity, fetal sex and PE). A further cohort of 250 PE and 250 control maternal and fetal samples are currently under analysis. Conclusions: These data support our hypothesis that defective EVT invasion associated with increased STOX1 transactivation is a precipitating factor in the development of PE. Funding: This work was funded by the CIHR MOP82811 http://dx.doi.org/10.1016/j.placenta.2013.06.164
P1.129. ASSESSMENT OF CARDIAC PARAMETERS IN LARGE FOR GESTATIONAL AGE INFANTS IN MOTHERS WITH &WITHOUT GESTATIONAL DIABETES: CORRELATION WITH PLACENTAL PATHOLOGY P. Charlagorla, H. Inany, M. Gudavalli, M. Chhabra, C. Salafia, B. Dygulska, P. Narula, A. Gad New York Methodist Hospital, Brooklyn/NY, USA Introduction: Large for gestational age (LGA) is defined as birth weight above the 90-th percentile for that gestational age. Maternal pre and gestational diabetes (GDM) and obesity are major risk factors leading to LGA babies. Perinatal hyperglycemia is thought to be the teratogen or causative agent, leading to major fetal complications, stillbirth, increased C-Sections and health care costs. Incidence of asymmetric septal hypertrophy (ASH) is of 31-38% in LGA newborns of GDM mothers, and 7% in nongestational diabetic mothers (NGDM). To this date, no study has distinguished and compared ASH findings in LGA newborns born to GDM/ NGDM mothers in comparison with placental pathology findings. Objectives: 1. Identify differences in placental pathology between GDM and NGDM mothers of LGA infants.
A55
Methodology: This is a retrospective study. Study subjects were LGA babies term newborns (GA 37- 40weeks) born to mothers with GDM (n¼31) and NGDM (n¼36). All babies were matched in terms of gestational age (GA) and mode of delivery and gender and underwent cardiac echocardiography (Echo) in the hospital before discharge as a part of routine care. Placental pathology reports are analyzed for placental parameters. Statistical analysis of categorical variables was carried out using chi-square and Fisher's exact tests as appropriate. Comparison of means was carried out using Student's t-test. A Pearson's correlation coefficient (r) calculation and multiple regression analysis performed on significant findings. Results: There are no significant differences between the 2 groups of LGA newborns. However, Body mass Index (BMI) was found to be higher in mothers with GDM. Placental thickness (not dimensions) was significantly increased in the GDM group but had no association to cardiac structural paramters. Correlating maternal BMI with different cardiac parameters in all LGA subjects showed a semi linear relationship with cardiac septal thickness (ST) (p¼0.03, (95%CI, 1.8-44). There was no relationship between maternal BMI and other cardiac parameters. Cardiac ST correlation with placental basal myofibers (p¼0.031) did not persist after controlling for other cardiac findings in regression analysis. Conclusion: 1. High maternal BMI is a major risk factor for GDM and ASH in the newborn. 2. Thick placenta could represent a marker for abnormal glucose metabolism during pregnancy. 3. Placental pathology exam has become to play a pivotal role in identifying newborns at risk for GDM related cardiac disease and opens the door for early interference. 4. Comparing the study findings to normal newborns in ongoing. http://dx.doi.org/10.1016/j.placenta.2013.06.165
P1.130. DEVELOPMENT OF ONLINE TEACHING MODULES FOR UNDERSTANDING PLACENTA PATHOLOGY David Grynspan 1, Benoit Desrochers 1, Andree Gruslin 2, 3, Laura McDonell 1, Julien Yockell-Lelievre 2, Christopher Ball 3, Nasser Al-Abbad 2, 3 1
Childrens Hospital of Eastern Ontario, Ontario, Canada; 2 The Ottawa Hospital, Ontario, Canada; 3 The University of Ottawa, Ontario, Canada
Introduction: A major trend in modern education has been the use of online instructional modules. The most notable example is the success of the Khan Academy, an online educational website which has several million viewers. These video modules are often made available free on video or file exchange sites such as youtube. The openness of these forums allows for rapid knowledge translation through the wide dissemination and global exchange of academic tutorials. A drawback is that the lack of confidentiality or control precludes use of direct clinical material. Thus abstract or conceptual fields such as mathematics, which can be taught using simple graphics, drawing and voice, are most amenable to online micro-tutorials as shown by the Khan Academy experience. Aim: The ability to map two-dimensional histological sections of placenta to the three dimensional structure is challenging due to the complexity of the branching structures and the numerous reflecting surfaces. We speculate that the education of pathology and obstetric trainees in this area would benefit from online instructional modules modeled after the Khan Academy tutorials since it is both an abstract and a visualization problem.