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Browsing by Subject "Maternal obesity"
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Item High early pregnancy body mass index is associated with alterations in first- and second-trimester angiogenic biomarkers(Elsevier, 2022) Beck, Celeste; Allshouse, Amanda; Silver, Robert M.; Grobman, William A.; Simhan, Hyagriv; Haas, David; Reddy, Uma M.; Blue, Nathan R.; Obstetrics and Gynecology, School of MedicineBackground: Obesity is associated with various placenta-mediated adverse pregnancy outcomes, including preeclampsia, preterm birth, and stillbirth. Mechanisms linking obesity with placental dysfunction are not completely understood. Objective: This study aimed to examine the relationship between early pregnancy body mass index and placental angiogenic biomarkers soluble fms-like tyrosine kinase-1, placental growth factor, and the soluble fms-like tyrosine kinase-1-to-placental growth factor ratio. Study design: We conducted secondary analyses of an existing substudy within a multisite, prospective observational cohort study of nulliparous pregnant women in the United States. First- and second-trimester maternal blood samples, first-trimester body mass index, and demographic, lifestyle, and pregnancy outcomes data were collected. Soluble fms-like tyrosine kinase-1 and placental growth factor concentrations were measured at 6 to 13 and 16 to 22 weeks of gestation for women (cases) who experienced one of several adverse pregnancy outcomes (delivery at <37 weeks of gestation, preeclampsia or eclampsia, birthweight for gestational age <5th percentile, or stillbirth) and for those who had none of those outcomes (controls). We used multivariable mixed-effects linear regression models to estimate the association of body mass index with angiogenic biomarkers at both time points. We evaluated mean change between first- and second-trimester biomarker concentrations using multivariable linear regression models. Lastly, we used logistic regression models to estimate the risk of a high second-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratio, using clinically established cutoffs for risk prediction. Results: Angiogenic biomarker and early pregnancy body mass index data were available for 2363 women (1467 with adverse pregnancy outcomes and 896 controls). High early pregnancy body mass index was associated with consistently lower soluble fms-like tyrosine kinase-1 concentrations across the first and second trimesters of pregnancy. We found lower first-trimester placental growth factor concentrations in the group with class II or III obesity (P<.001) and lower second-trimester placental growth factor concentrations among groups who were overweight, with class I obesity, and class II or III obesity (P<.001). For every unit increase in early pregnancy body mass index, there was a -4.4 pg/mL (95% confidence interval, -3.6 to -5.2) smaller mean increase in placental growth factor concentrations between the first and second trimesters of pregnancy. These differences resulted in significantly lower mean first-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratios among groups who were overweight, with class I obesity, and class II or III obesity (P<.05) and in a significantly higher second-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratio among the group with class II or III obesity (P<.001), compared with the group with normal body mass index. Each unit of increase in body mass index was associated with a 0.5 (95% confidence interval, 0.3-0.7) greater mean increase in the soluble fms-like tyrosine kinase-1-to-placental growth factor ratio between the first and second trimesters of pregnancy. In stratified analyses, associations between body mass index and angiogenic biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor were similar in nonadverse pregnancy outcome and adverse pregnancy outcome subgroups, whereas associations between body mass index and the soluble fms-like tyrosine kinase-1-to-placental growth factor ratio were attenuated in the subgroups. Participants in the group with class II or III obesity were 3.13 (95% confidence interval, 1.15-8.49) times more likely than participants with normal weight to have a second-trimester ratio of ≥38 in univariate analysis. Conclusion: High early pregnancy body mass index was associated with lower soluble fms-like tyrosine kinase-1 and placental growth factor concentrations across early pregnancy. Maternal body mass was inversely associated with first-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratios and positively associated with second-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratios, driven by a diminished rise in placental growth factor between the first and second trimesters of pregnancy. Women with class II or III obesity have an increased risk of a high second-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratio associated with placental dysfunction.Item Offspring of Obese Dams Exhibit Sex-Differences in Pancreatic Heparan Sulfate Glycosaminoglycans and Islet Insulin Secretion(Frontiers Media, 2021-05-24) Casasnovas, Jose; Damron, Christopher Luke; Jarrell, James; Orr, Kara S.; Bone, Robert N.; Archer-Hartmann, Stephanie; Azadi, Parastoo; Kua, Kok Lim; Pediatrics, School of MedicineOffspring of obese mothers suffer higher risks of type 2 diabetes due to increased adiposity and decreased β cell function. To date, the sex-differences in offspring islet insulin secretion during early life has not been evaluated extensively, particularly prior to weaning at postnatal day 21 (P21). To determine the role of maternal obesity on offspring islet insulin secretion, C57BL/6J female dams were fed chow or western diet from 4 weeks prior to mating to induce maternal obesity. First, offspring of chow-fed and obese dams were evaluated on postnatal day 21 (P21) prior to weaning for body composition, glucose and insulin tolerance, and islet phasic insulin-secretion. Compared to same-sex controls, both male and female P21 offspring born to obese dams (MatOb) had higher body adiposity and exhibited sex-specific differences in glucose tolerance and insulin secretion. The male MatOb offspring developed the highest extent of glucose intolerance and lowest glucose-induced insulin secretion. In contrast, P21 female offspring of obese dams had unimpaired insulin secretion. Using SAX-HPLC, we found that male MatOb had a decrease in pancreatic heparan sulfate glycosaminoglycan, which is a macromolecule critical for islet health. Notably, 8-weeks-old offspring of obese dams continued to exhibit a similar pattern of sex-differences in glucose intolerance and decreased islet insulin secretion. Overall, our study suggests that maternal obesity induces sex-specific changes to pancreatic HSG in offspring and a lasting effect on offspring insulin secretion, leading to the sex-differences in glucose intolerance.Item Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation(Wiley, 2018-12-01) Puppala, Sobha; Li, Cun; Glenn, Jeremy P.; Saxena, Romil; Gawrieh, Samer; Quinn, Amy; Palarczyk, Jennifer; Dick, Edward J.; Nathanielsz, Peter W.; Cox, Laura A.; Medicine, School of MedicineKey points Maternal obesity (MO) and exposure to a high‐fat, high‐simple‐carbohydrate diet during pregnancy predisposes offspring to obesity, metabolic and cardiovascular disorders in later life. Underlying molecular pathways and potential epigenetic factors that are dysregulated in MO were identified using unbiased transcriptomic methods. There was increased lipid accumulation and severe steatosis in the MO baboon fetal liver suggesting that these offspring are on an early trajectory of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis. Abstract Maternal obesity (MO) increases offspring cardiometabolic disease risk. Altered fetal liver development in response to the challenge of MO has metabolic consequences underlying adverse offspring life‐course health outcomes. Little is known about the molecular pathways and potential epigenetic changes regulating primate fetal liver responses to MO. We hypothesized that MO would induce fetal baboon liver epigenetic changes resulting in dysregulation of key metabolic pathways that impact lipid metabolism. MO was induced prior to pregnancy by a high‐fat, high‐fructose diet. Unbiased gene and microRNA (small RNA Seq) abundance analyses were performed on fetal baboon livers at 0.9 gestation and subjected to pathway analyses to identify fetal liver molecular responses to MO. Fetal baboon liver lipid and glycogen content were quantified by the Computer Assisted Stereology Toolbox. In response to MO, fetal livers revealed dysregulation of TCA cycle, proteasome, oxidative phosphorylation, glycolysis and Wnt/β‐catenin signalling pathways together with marked lipid accumulation supporting our hypothesis that multiple pathway dysregulation detrimentally impacts lipid management. This is the first study of MO programming of the non‐human primate fetal liver using unbiased transcriptome analysis to detect changes in hepatic gene expression levels and identify potential microRNA epigenetic regulators of metabolic disruption.Item The moderating role of the built environment in prenatal lifestyle interventions(Springer Nature, 2021) Phelan, Suzanne; Marquez, Fred; Redman, Leanne M.; Arteaga, Sonia; Clifton, Rebecca; Grice, Brian A.; Haire-Joshu, Debra; Martin, Corby K.; Myers, Candice A.; Pomeroy, Jeremy; Vincent, Eileen; Van Horn, Linda; Peaceman, Alan; Ashby-Thompson, Maxine; Gallagher, Dympna; Pi-Sunyer, Xavier; Boekhoudt, Trisha; Drews, Kimberly; Brown, Greg; LIFE-Moms consortium; Emergency Medicine, School of MedicineThis study examined whether the neighborhood built environment moderated gestational weight gain (GWG) in LIFE-Moms clinical trials. Participants were 790 pregnant women (13.9 weeks’ gestation) with overweight or obesity randomized within four clinical centers to standard care or lifestyle intervention to reduce GWG. Geographic information system (GIS) was used to map the neighborhood built environment. The intervention relative to standard care significantly reduced GWG (coefficient = 0.05; p = 0.005) and this effect remained significant (p < 0.03) after adjusting for built environment variables. An interaction was observed for presence of fast food restaurants (coefficient=−0.007; p = 0.003). Post hoc tests based on a median split showed that the intervention relative to standard care reduced GWG in participants living in neighborhoods with lower fast food density 0.08 [95% CI, 0.03,0.12] kg/week (p = 0.001) but not in those living in areas with higher fast food density (0.02 [−0.04, 0.08] kg/week; p = 0.55). Interaction effects suggested less intervention efficacy among women living in neighborhoods with more grocery/convenience stores (coefficient = −0.005; p = 0.0001), more walkability (coefficient −0.012; p = 0.007) and less crime (coefficient = 0.001; p = 0.007), but post-hoc tests were not significant. No intervention x environment interaction effects were observed for total number of eating establishments or tree canopy. Lifestyle interventions during pregnancy were effective across diverse physical environments. Living in environments with easy access to fast food restaurants may limit efficacy of prenatal lifestyle interventions, but future research is needed to replicate these findings.