- Email: [email protected]
552: Programmed insulin resistance of offspring of obese mothers
Poster Session III
ajog.org GA were also significantly lower (19.3 22.2 vs 5.22 7.2.; p¼0.01).
and 12 months (retroperitoneal) of age from male offspring. Protein expression of Wnt10b and b-catenin and PPARg were analyzed. RESULTS: Newborn MO males were heavier than Controls (1.550.09 vs 1.310.01 g; P<0.05). Consistent with our hypothesis, MO male newborns had downregulated Wnt10b (0.5-fold; P<0.05) and bcatenin (0.7-fold; P<0.05) and upregulated PPARg levels (2-fold; P<0.05). At 12 months of age, MO males demonstrated obesity (503 vs 412 g; p<0.001) with significantly increased body fat (472 vs 373 %; p<0.001) as compared to controls, and expressed further decreases in levels of Wnt10b (0.3-fold; P<0.05) and b-catenin (0.4fold; P<0.05) and further increases in PPARg (2.8-fold; P<0.05), as compared to newborn. CONCLUSION: Suppression of Wnt10b/ b-catenin and increased PPARg signalling represents a key pathway promoting programmed adipogenesis and obesity. Whereas maternal obesity activates the newborn adipose PPARg pathway, it is further potentiated by offspring obesity, suggesting a feed-forward cycle. Interruption of the obesity-mediated PPARg in offspring may prevent programmed adult obesity.
552 Programmed insulin resistance of offspring of obese mothers Mina Desai1, Guang Han1, Elaheh Mossayebi1, Marie H. Beall2, Michael G. Ross1 1
Los Angeles Biomedical Research Institute, Torrance, CA, 2L.A. Perinatal Assoc., Los Angeles, CA
CONCLUSION: The reduced EFW and BW in the group of FGR with
abnormal Dopplers provides validity of the comparison groups. Both absolute and normalized UVF correlate best with UmA Doppler. Overall, there was no significant relationship of UVF with MCA or the CPR. The abnormal UVF and UmA PI are consistent with abnormal vasculature structure and vasoreactivity described in the FGR placenta. In contrast, the MCA and CPR abnormalities seen in late preterm FGR are related to hypoxia and appear to act independently of UVF and UmA PI. (Funded by The Perelman IUGR Study)
551 A critical adipose pathway promotes both newborn and programmed offspring obesity Mina Desai1, Guang Han1, Kavita Narwani1, Marie H. Beall2, Robert H. Lane3, Michael G. Ross1 1
Los Angeles Biomedical Research Institute, Torrance, CA, 2L.A. Perinatal Assoc., Los Angeles, CA, 3Medical College of Wisconsin, Miliwaukee, WI
OBJECTIVE: Infants born to obese mothers (MO) are at markedly increased risk of childhood and adult obesity, in part a result of programmed fat accumulation (adipogenesis). We have shown that the increased offspring adiposity is mediated via newborn upregulation of adipogenic transcription factor, PPARg, which promotes adipocyte differentiation, resulting in increased number of adipocytes. PPARg-mediated adipogenesis is regulated by a Wnt10b signal pathway, as follows: activation of Wnt10b and b-catenin suppresses PPARg expression. We hypothesized that in MO offspring, Wnt10b/ b-catenin pathway increases PPARg and thus enhances adipogenesis contributing to programmed offspring obesity. STUDY DESIGN: Female mice were fed either a control (10% k/cal) or high fat (45% k/cal) diet to create maternal obesity (MO) prior to mating, and throughout pregnancy and lactation. All offspring were weaned to normal diet. Adipose tissue was obtained at 1 day (inguinal)
OBJECTIVE: Offspring born to obese mothers are often larger at birth, and have a markedly increased risk of obesity and insulin resistant diabetes in later life. As the prevalence of obesity among pregnant women continues to rise, increasing number of children are exposed to an ’obese intrauterine environment’ during development. Insulin resistance results in reduced glucose uptake, manifest importantly in skeletal muscle, the predominant site of insulin-mediated glucose uptake. We hypothesized that maternal obesity (OB) reduces offspring lean body mass (e.g., muscle) and decreases insulin-stimulated skeletal muscle glucose uptake. STUDY DESIGN: Female mice were fed either a control (10% k/cal) or high fat (45% k/cal) diet to create maternal obesity (OB) prior to mating, and diets continued throughout pregnancy and lactation. After birth, all offspring were weaned to normal diet. At 14 months of age, male offspring underwent DEXA scan and GTT. After overnight fast, males were sacrificed, blood glucose levels analyzed and 6 mg of muscle strips (carpi radialis) were incubated with 10mM of glucose with (10 mg/ml) and without insulin for 1h and glucose uptake determined. Values (meanSE) are expressed as percentage of Control without insulin. RESULTS: At 1 day of age, OB males were heavier (1.550.09 vs 1.310.01 g; p<0.05) than Controls. At 14 months of age, OB males were obese (503 vs 412 g; p<0.001) though with significantly decreased lean body mass (452 vs 583 %; p<0.001) and increased blood glucose levels (1867 vs 1246 mg/dl; p<0.001) as compared to controls. Further, OB males had impaired GTT. Skeletal muscle of OB adult males showed similar basal glucose uptake as controls. Insulin stimulated glucose uptake in both Control and OB muscle, though the response was was significantly decreased in OB offspring (figure 1). CONCLUSION: Maternal obesity programs offspring with reduced lean body mass and reduced skeletal muscle insulin-mediated glucose uptake, contributing to adult insulin resistance.
Supplement to JANUARY 2017 American Journal of Obstetrics & Gynecology
S325
Poster Session III
ajog.org categories of infections morbidity are presented in the table. The association between CD and long-term pediatric infectious morbidity remained significant in a Cox proportional hazards model, controlling for maternal age, preterm births, and birth weight (aHR 1.45; 95% CI 1.37-1.53). CONCLUSION: Children delivered by Cesarean are at an increased risk for pediatric infectious morbidity, as compared with children delivered vaginally.
553 Elective cesarean delivery and pediatric infectious morbidity of the offspring - results of a population based cohort of up to 18 years Tamar Wainstock1, Asnat Walfisch2, Ilana Shoham-Vardi1, Idit Segal3, Ruslan Sergienko1, Eyal Sheiner2,4 1
Ben Gurion University of the Negev, Beer- Sheva, Israel, 2Department of Obstetrics and Gynecology, Soroka University Medical Center, Beer- Sheva, Israel, 3Ministry of Health, Jerusalem, Israel, 4Ben-Gurion University of the Negev, Beer- Sheva, Israel
OBJECTIVE: Cesarean delivery (CD) has been shown to affect the
newborn’s microbiome. We aimed to study a possible association between mode of delivery and the risk for infectious diseases of the offspring, during a follow- up period of up to 18 years. STUDY DESIGN: A population based cohort analysis was performed comparing different subtypes of infectious morbidity leading to hospitalization among children (up to the age of 18 years) based on mode delivery: vaginal (VD) or CD. Data on pregnancy course and outcome, mode of delivery, and later offspring hospitalization were collected from the same database of a single tertiary center in the region. All singleton deliveries between the years 1991-2013 were included in the analysis. Exclusion criteria were congenital malformations, perinatal deaths, instrumental deliveries, pregnancy, delivery, and fetal complications (including: maternal hypertensive disorders and gestational diabetes, labor dystocia, fetal distress, labor induction, and fetal growth restriction). Kaplan-Meier survival curve was constructed to compare cumulative infectious disease hospitalization incidence based on mode of delivery, and a Cox proportional hazard model was used to control for confounders including gestational age and maternal factors. RESULTS: During the study period, 138 910 newborns met the inclusion criteria: 13 206 (9.5%) were delivered by CD, and 125 704 (91.5%) were delivered vaginally. During the follow up period (0-18 years, median 10.22), 13 054 (9.4%) were hospitalized (at least once) due to infectious morbidity: 12.0% among the CD children, and 9.1% of the VD (RR¼1.36; 95%CI 1.28-1.43; incidence density rates for first hospitalization: CD 15.22/1000 person years; VD 9.06/1000 person years; Kaplan-Meier Log rank p<0.001, figure). Selected
554 Low apgar score in term newborns and long term gastro-intestinal morbidity, a population based cohort study with up to 18 years of follow up Tamar Wainstock1, Asnat Walfisch2, Ilana Shoham- Vardi1, Idit Segal3, Ruslan Sergienko1, Eyal Sheiner2,4 1
Ben Gurion University of the Negev, Beer- Sheva, Israel, 2Department of Obstetrics and Gynecology, Soroka University Medical Center, Beer- Sheva, Israel, 3Ministry of Health, Jerusalem, Israel, 4Ben-Gurion University of the Negev, Beer -Sheva, Israel
OBJECTIVE: Low Apgar scores (<7) measured at age 5 minutes can predict short- term infant morbidity and mortality. We aimed to study the possible association between low 5 minutes Apgar scores in term newborns and their long-term gastro-intestinal (GI) related morbidity, during a follow- up of up to 18 years. STUDY DESIGN: A population based cohort analysis was performed comparing total and different subtypes of GI related pediatric hospitalizations (up to the age of 18 years) among newborns with normal (7) and low (<7) 5 minutes Apgar scores. The analysis included all term singletons born between the years 1999-2013 at a single tertiary regional medical center. Infants with congenital malformations and all perinatal deaths were excluded from the long term analysis. GI related morbidities included hospitalizations involving a pre-defined set of ICD-9 codes, as recorded in the hospital medical records. A KaplanMeier survival curve was constructed to compare the cumulative GI morbidity, and a Cox proportional hazards model was used to adjust for suspected confounders. RESULTS: The study population, including 223 224 term singletons, was followed for an average of 10.026.04 years (0- 18 years, median 10.25) following discharge from birth hospitalization. Low 5 minutes
S326 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2017
ajog.org GA were also significantly lower (19.3 22.2 vs 5.22 7.2.; p¼0.01).
and 12 months (retroperitoneal) of age from male offspring. Protein expression of Wnt10b and b-catenin and PPARg were analyzed. RESULTS: Newborn MO males were heavier than Controls (1.550.09 vs 1.310.01 g; P<0.05). Consistent with our hypothesis, MO male newborns had downregulated Wnt10b (0.5-fold; P<0.05) and bcatenin (0.7-fold; P<0.05) and upregulated PPARg levels (2-fold; P<0.05). At 12 months of age, MO males demonstrated obesity (503 vs 412 g; p<0.001) with significantly increased body fat (472 vs 373 %; p<0.001) as compared to controls, and expressed further decreases in levels of Wnt10b (0.3-fold; P<0.05) and b-catenin (0.4fold; P<0.05) and further increases in PPARg (2.8-fold; P<0.05), as compared to newborn. CONCLUSION: Suppression of Wnt10b/ b-catenin and increased PPARg signalling represents a key pathway promoting programmed adipogenesis and obesity. Whereas maternal obesity activates the newborn adipose PPARg pathway, it is further potentiated by offspring obesity, suggesting a feed-forward cycle. Interruption of the obesity-mediated PPARg in offspring may prevent programmed adult obesity.
552 Programmed insulin resistance of offspring of obese mothers Mina Desai1, Guang Han1, Elaheh Mossayebi1, Marie H. Beall2, Michael G. Ross1 1
Los Angeles Biomedical Research Institute, Torrance, CA, 2L.A. Perinatal Assoc., Los Angeles, CA
CONCLUSION: The reduced EFW and BW in the group of FGR with
abnormal Dopplers provides validity of the comparison groups. Both absolute and normalized UVF correlate best with UmA Doppler. Overall, there was no significant relationship of UVF with MCA or the CPR. The abnormal UVF and UmA PI are consistent with abnormal vasculature structure and vasoreactivity described in the FGR placenta. In contrast, the MCA and CPR abnormalities seen in late preterm FGR are related to hypoxia and appear to act independently of UVF and UmA PI. (Funded by The Perelman IUGR Study)
551 A critical adipose pathway promotes both newborn and programmed offspring obesity Mina Desai1, Guang Han1, Kavita Narwani1, Marie H. Beall2, Robert H. Lane3, Michael G. Ross1 1
Los Angeles Biomedical Research Institute, Torrance, CA, 2L.A. Perinatal Assoc., Los Angeles, CA, 3Medical College of Wisconsin, Miliwaukee, WI
OBJECTIVE: Infants born to obese mothers (MO) are at markedly increased risk of childhood and adult obesity, in part a result of programmed fat accumulation (adipogenesis). We have shown that the increased offspring adiposity is mediated via newborn upregulation of adipogenic transcription factor, PPARg, which promotes adipocyte differentiation, resulting in increased number of adipocytes. PPARg-mediated adipogenesis is regulated by a Wnt10b signal pathway, as follows: activation of Wnt10b and b-catenin suppresses PPARg expression. We hypothesized that in MO offspring, Wnt10b/ b-catenin pathway increases PPARg and thus enhances adipogenesis contributing to programmed offspring obesity. STUDY DESIGN: Female mice were fed either a control (10% k/cal) or high fat (45% k/cal) diet to create maternal obesity (MO) prior to mating, and throughout pregnancy and lactation. All offspring were weaned to normal diet. Adipose tissue was obtained at 1 day (inguinal)
OBJECTIVE: Offspring born to obese mothers are often larger at birth, and have a markedly increased risk of obesity and insulin resistant diabetes in later life. As the prevalence of obesity among pregnant women continues to rise, increasing number of children are exposed to an ’obese intrauterine environment’ during development. Insulin resistance results in reduced glucose uptake, manifest importantly in skeletal muscle, the predominant site of insulin-mediated glucose uptake. We hypothesized that maternal obesity (OB) reduces offspring lean body mass (e.g., muscle) and decreases insulin-stimulated skeletal muscle glucose uptake. STUDY DESIGN: Female mice were fed either a control (10% k/cal) or high fat (45% k/cal) diet to create maternal obesity (OB) prior to mating, and diets continued throughout pregnancy and lactation. After birth, all offspring were weaned to normal diet. At 14 months of age, male offspring underwent DEXA scan and GTT. After overnight fast, males were sacrificed, blood glucose levels analyzed and 6 mg of muscle strips (carpi radialis) were incubated with 10mM of glucose with (10 mg/ml) and without insulin for 1h and glucose uptake determined. Values (meanSE) are expressed as percentage of Control without insulin. RESULTS: At 1 day of age, OB males were heavier (1.550.09 vs 1.310.01 g; p<0.05) than Controls. At 14 months of age, OB males were obese (503 vs 412 g; p<0.001) though with significantly decreased lean body mass (452 vs 583 %; p<0.001) and increased blood glucose levels (1867 vs 1246 mg/dl; p<0.001) as compared to controls. Further, OB males had impaired GTT. Skeletal muscle of OB adult males showed similar basal glucose uptake as controls. Insulin stimulated glucose uptake in both Control and OB muscle, though the response was was significantly decreased in OB offspring (figure 1). CONCLUSION: Maternal obesity programs offspring with reduced lean body mass and reduced skeletal muscle insulin-mediated glucose uptake, contributing to adult insulin resistance.
Supplement to JANUARY 2017 American Journal of Obstetrics & Gynecology
S325
Poster Session III
ajog.org categories of infections morbidity are presented in the table. The association between CD and long-term pediatric infectious morbidity remained significant in a Cox proportional hazards model, controlling for maternal age, preterm births, and birth weight (aHR 1.45; 95% CI 1.37-1.53). CONCLUSION: Children delivered by Cesarean are at an increased risk for pediatric infectious morbidity, as compared with children delivered vaginally.
553 Elective cesarean delivery and pediatric infectious morbidity of the offspring - results of a population based cohort of up to 18 years Tamar Wainstock1, Asnat Walfisch2, Ilana Shoham-Vardi1, Idit Segal3, Ruslan Sergienko1, Eyal Sheiner2,4 1
Ben Gurion University of the Negev, Beer- Sheva, Israel, 2Department of Obstetrics and Gynecology, Soroka University Medical Center, Beer- Sheva, Israel, 3Ministry of Health, Jerusalem, Israel, 4Ben-Gurion University of the Negev, Beer- Sheva, Israel
OBJECTIVE: Cesarean delivery (CD) has been shown to affect the
newborn’s microbiome. We aimed to study a possible association between mode of delivery and the risk for infectious diseases of the offspring, during a follow- up period of up to 18 years. STUDY DESIGN: A population based cohort analysis was performed comparing different subtypes of infectious morbidity leading to hospitalization among children (up to the age of 18 years) based on mode delivery: vaginal (VD) or CD. Data on pregnancy course and outcome, mode of delivery, and later offspring hospitalization were collected from the same database of a single tertiary center in the region. All singleton deliveries between the years 1991-2013 were included in the analysis. Exclusion criteria were congenital malformations, perinatal deaths, instrumental deliveries, pregnancy, delivery, and fetal complications (including: maternal hypertensive disorders and gestational diabetes, labor dystocia, fetal distress, labor induction, and fetal growth restriction). Kaplan-Meier survival curve was constructed to compare cumulative infectious disease hospitalization incidence based on mode of delivery, and a Cox proportional hazard model was used to control for confounders including gestational age and maternal factors. RESULTS: During the study period, 138 910 newborns met the inclusion criteria: 13 206 (9.5%) were delivered by CD, and 125 704 (91.5%) were delivered vaginally. During the follow up period (0-18 years, median 10.22), 13 054 (9.4%) were hospitalized (at least once) due to infectious morbidity: 12.0% among the CD children, and 9.1% of the VD (RR¼1.36; 95%CI 1.28-1.43; incidence density rates for first hospitalization: CD 15.22/1000 person years; VD 9.06/1000 person years; Kaplan-Meier Log rank p<0.001, figure). Selected
554 Low apgar score in term newborns and long term gastro-intestinal morbidity, a population based cohort study with up to 18 years of follow up Tamar Wainstock1, Asnat Walfisch2, Ilana Shoham- Vardi1, Idit Segal3, Ruslan Sergienko1, Eyal Sheiner2,4 1
Ben Gurion University of the Negev, Beer- Sheva, Israel, 2Department of Obstetrics and Gynecology, Soroka University Medical Center, Beer- Sheva, Israel, 3Ministry of Health, Jerusalem, Israel, 4Ben-Gurion University of the Negev, Beer -Sheva, Israel
OBJECTIVE: Low Apgar scores (<7) measured at age 5 minutes can predict short- term infant morbidity and mortality. We aimed to study the possible association between low 5 minutes Apgar scores in term newborns and their long-term gastro-intestinal (GI) related morbidity, during a follow- up of up to 18 years. STUDY DESIGN: A population based cohort analysis was performed comparing total and different subtypes of GI related pediatric hospitalizations (up to the age of 18 years) among newborns with normal (7) and low (<7) 5 minutes Apgar scores. The analysis included all term singletons born between the years 1999-2013 at a single tertiary regional medical center. Infants with congenital malformations and all perinatal deaths were excluded from the long term analysis. GI related morbidities included hospitalizations involving a pre-defined set of ICD-9 codes, as recorded in the hospital medical records. A KaplanMeier survival curve was constructed to compare the cumulative GI morbidity, and a Cox proportional hazards model was used to adjust for suspected confounders. RESULTS: The study population, including 223 224 term singletons, was followed for an average of 10.026.04 years (0- 18 years, median 10.25) following discharge from birth hospitalization. Low 5 minutes
S326 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2017