435: Mechanism of second generation obesity: maternal obesity programs offspring hyperphagia

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<ul><li><p>in combination with EPO reduced the extent of the damage. Func-tional test indicate a significant reduction of spastic paresis.CONCLUSION: Transplantation of human placenta-derived MSC intothe lateral ventricle of neonatal rats / EPO is possible. Morpho-logic changes in the reciepients brain indicate neuroprotective effectsof the stem cell therapy in both investigated groups. Further experi-ments will assess the window of opportunity of stem cell therapy inperinatal brain damage.</p><p>433 Predictors of abdominal wall closurein neonates with gastroschisisMatthew Loichinger1, Tana Kim3, Randall Kuhlmann2,Erika Peterson21University of Hawaii John A. Burns School ofMedicine,Maternal-FetalMedicine, Honolulu, HI, 2Medical College ofWisconsin,Maternal-FetalMedicine,Milwaukee,WI, 3Medical College ofWisconsin, OB/GYN,Milwaukee,WIOBJECTIVE: To evaluate closure outcomes for neonates with gastros-chisis born at a single tertiary center.STUDY DESIGN: This is a retrospective analysis of 151 cases of fetalgastroschisis during an 11 year period from September 2001 to De-cember of 2011. After initial chart review, 11 cases met exclusion cri-teria and 140 cases were stratified into the following gestational agecategories: early pre-term (35.0 weeks), late pre-term (35.0-36.6weeks), and term (37.0weeks).Datawere then abstracted frombothmaternal and fetal charts. The relationship between gestational age atthe time of delivery and type of closurewas determined. The followingconfounding variables were accounted for: fetal weight, bowel dila-tion, mode of delivery, respiratory distress syndrome (RDS), necro-tizing enterocolitis (NEC), bowel atresia, antenatal steroids, and shortgut syndrome. Univariate analysis was performed using the Kruskall-Wallis Test and Fishers Exact Test as appropriate. Any variables witha p-value of 0.05 or less were included in the multivariate analysis.Multivariate regression was performed and a p-value less than 0.05was considered statistically significant.RESULTS: Gestational age at the time of delivery did not have a statis-tically significant correlation with the type of abdominal wall closure(p0.14). However, there was a statistically significant correlationbetween fetal weight at the time of delivery and primary closure(p0.04, OR1.091, 95% CI 1.004-1.185). For every 100 gramincrease in weight there was a 9% increase in the odds of primaryclosure.CONCLUSION: Increasing fetal weight at the time of delivery is a betterpredictor of primary closure than gestational age at the time of deliv-ery for neonates with gastroschisis.</p><p>434 Maternal high fat diet exposure is associatedwith a disruption of the fetal thyroid axis in anon-human primate modelMelissa Suter1, Haleh Sangi-Haghpeykar1, Lori Showalter1,Cindy Shope1, Min Hu1, Alan Harris1, Sarah Williams2,Robert Lane3, Kevin Grove2, Kjersti Aagaard11Baylor College ofMedicine, Division ofMaternal-Fetal Medicine,Departments of Obstetrics and Gynecology, Cell andMolecular BIology, andMolecular andHumanGenetics, Houston, TX, 2OregonHealth and SciencesUniversity, OregonNational Primate Research Center, Beaverton, OR,3University of Utah, Pediatrics, Salt Lake City, UTOBJECTIVE: Thyroid hormone (TH) is an essential regulator of bothfetal development and energy expenditure. Although the associationbetween sub-clinical hypothyroidism and obesity has been well stud-ied, a causal relationship has yet to be established. TH synthesis andrelease is orchestrated through tight regulation of gene expressionwithin the hypothalamic-pituitary-thyroid axis (Fig. 1A). The balancebetween bioactive free T3 (fT3) and free T4 (fT4) produced by thethyroid gland is maintained through tissue specific expression of thedeiodinase, iodothyronine (DIO) genes.We have previously reportedthat in utero exposure to a maternal high fat diet (HFD) is associated</p><p>with reduced fetal fT4. In this study we sought to determine if HFDexposure disrupts expression of genes involved in maintaining THhomeostasis in the fetus.STUDY DESIGN: Pregnant macaques were fed either control (13% fat,n4) or HF (35% fat, n4) diet. On e130, fetal liver, thyroid glandand hypothalamic tissues were obtained and snap frozen. Chromatin,DNA, RNA and protein were extracted for use in extensive molecularcharacterization of the fetal thyroid axis.RESULTS: Expression of DIO2 and DIO3 is significantly decreased inthe fetal liver with maternal HFD exposure (0.3-fold, p0.003; 0.5-fold, p0.001). DIO3 is similarly decreased in fetal hypothalamus(0.5-fold, p0.039). Genes involved in TH synthesis and release(TRH, TSHR, TG, TPO, SLC5A5) are all significantly decreased ineither the hypothalamus or thyroid gland with HFD exposure (Fig.1B).CONCLUSION: In light of our previous findings of alterations of thehepatic histone code, these data are consistent with the deleteriouseffects of exposure to a maternal HFD extending to transcriptionaland epigenetic alterations of the fetal thyroid axis. We speculate thatmaternal high fat diet exposure in utero may set the stage for later inlife obesity in part by disrupting the transcriptional program neces-sary to maintain thyroid homeostasis in fetal life.</p><p>435 Mechanism of second generation obesity: maternalobesity programs offspring hyperphagiaMina Desai1, Michael Ross1, Tie Li11LABioMed at Harbor-UCLAMed. Ctr., Obstetrics and Gynecology,Torrance, CAOBJECTIVE: As the prevalence of obesity among pregnant women con-tinues to rise, increasing number of children are exposed to an obeseintrauterine environment. Maternal obesity has been shown to in-crease the risk of offspring obesity, due in part to altered developmentof the hypothalamic appetite center (arcuate nucleus; ARC). TheARCcontains two populations of neurons with opposing actions on foodintake: ARC appetite (AgRP; agouti-related protein) and ARC satiety(POMC; pro-opiomelanocortin). We hypothesized that maternalobesity impacts fetal hypothalamic ARC development, resulting in anincrease in appetite (AgRP) versus satiety (POMC) neurons.STUDY DESIGN: At 3 week of age, female rats were weaned to high fat(HF: 60% k/cal) or (control, 10% k/cal) diet. At 11 weeks of age, theserats were mated and continued on their respective diets during preg-nancy and lactation. After birth, litter size was standardized, pupsnursed by the same dams and weaned to a normal diet. Brains were</p><p>Epigenomic and transcriptional modificationof the fetal thryoid axis by the maternal diet</p><p>A, The hypothalamic-pituitary-thyroid (HPT) axis coordinates TH produc-tion. TSH is bound by the TSHR in the thyroid gland, which activates thedownstream genes necessary for TH production and release (TG, TPO andSLC5A5); B, The HPT axis is epigenomically modified with significant re-duction following maternal HFD exposure (n4/group).</p><p>www.AJOG.org Doppler Assess, Fetus, Prematurity, U/S, Med-Surg-Diseases Poster Session III</p><p>Supplement to JANUARY 2013 American Journal of Obstetrics&amp; Gynecology S189</p></li><li><p>collected from newborn and adult (6 months) male offspring andnewborn hypothalami and adult ARC dissected. Protein expression(Western Blot) of AgRP and POMC was determined and normalizedvalues presented as fold change.RESULTS: HF offspring had comparable body weight as Controls atbirth, but were markedly heavier at 6 months (75814 vs 64515 g).Increased HF weight gain was apparent both during nursing and fol-lowing weaning, with evidence of increased food intake. At 1 day ofage, HF exhibited increased hypothalamic expression of AgRP (1.4-fold) as compared to Controls. At 6 months of age, HF showed con-tinued increased expression of ARC AgRP (1.5-fold) and decreasedPOMC (0.5-fold) expression.CONCLUSION: In HF obese offspring, expression of the appetite factorAgRP is increased and the satiety factor POMC is decreased. Infantsborn to obese women may be at risk of childhood and adult obesitysecondary to an increased proportion of appetite versus satietyneurons.</p><p>436 The placental factor in early and latenormotensive growth restrictionMichal Kovo1, Letizia Schreiber2, Avi Ben-Haroush3, Guy Cohen1,Eran Weiner1, Abraham Golan1, Jacob Bar11EdithWolfsonMedical Center, Holon, affiliated with Sackler Faculty ofMedicine, Tel Aviv University, Obstetrics &amp;Gynecology, Tel-Aviv, Israel,2EdithWolfsonMedical Center, Holon, affiliated with Sackler Faculty ofMedicine, Tel Aviv University, Department of Pathology, Tel-Aviv, Israel,3RabinMedical Center, Petah-Tikva affiliated with Sackler Faculty ofMedicine, Tel Aviv University, Obstetrics and Gynecology, Tel-Aviv, IsraelOBJECTIVE: Recent studies suggested that fetal growth restriction(FGR) canbe divided to early-onset (before 34weeks of gestation) andto late-onset FGR (after 34 weeks of gestation), by demonstratingdifferences in severity, pregnancy outcome and Doppler indices be-tween the groups. However, the placental component has not beencompared between the groups yet. Therefore, we compared placentalhistology between small for gestational age (SGA) neonates and be-tween control neonates appropriate for gestational age (AGA).STUDY DESIGN: Placentas from normotensive women who deliveredneonates with birth-weight 10th percentile of the local populationgrowth curves (FGR group), and placentas from healthy women whodelivered AGA neonates (AGA group), between 24-42 weeks of ges-tation, were analyzed by a single pathologist. Placental lesions wereclassified to lesions consistent with maternal underperfusion, lesionsconsistent with fetal thrombo-occlusive disease and inflammatory le-sions. Placental findings were compared between those who deliveredbefore and after 34 weeks of gestation.RESULTS: The early-onset FGR group (n24) was characterized by ahigher rate of vascular lesions related to maternal underperfusion,41.7% vs. 8.7% than in the late-FGR group (n334), p0.001. Com-pared to AGA controls delivered34 weeks (n68), the early-onsetFGR group had more villous lesions related to maternal underperfu-sion, 70.8% vs. 5.9%, P0.001, and less inflammatory lesions, 8.3%vs. 58.8%, p0.001. Placentas from late-onset FGR group had morevillous lesions related to maternal underperfusion, 57% vs. 19%,p0.001, and more lesions consistent with fetal thrombo-occlusivedisease, 26.3% vs. 8.5%, p0.001, compared with AGA controls(n153) delivered34 weeks.CONCLUSION: Placentas from pregnancies with late-onset FGR dem-onstrate less severe maternal vascular supply lesions than placentasfrom early-onset FGR, and more fetal vascular supply lesions than incontrols, suggesting differentmechanism(s) of placental dysfunction.</p><p>437 The impact of change in pregnancybody mass index on macrosomiaMorgan Swank1, Aaron Caughey2, Christine Farinelli1, ElliottMain3, Kathryn Melsop3, William Gilbert4, Judith Chung11University of California, Irvine,Maternal Fetal Medicine, Orange, CA,2OregonHealth &amp; Science University, Maternal Fetal Medicine, Portland,OR, 3CaliforniaMaternal Quality Care Collaborative, (CMQCC), Stanford,CA, 4SutterMedical Center, Maternal Fetal Medicine, Sacramento, CAOBJECTIVE: To examine the impact of changes in body mass index(BMI) during pregnancy on the incidence of macrosomia.STUDY DESIGN: This is a retrospective cohort study using linked birthcertificate and discharge diagnosis data (All-California, Rapid-Cycle,Maternal/Infant Database) from the year 2007. Adjusted odds ratios(aOR) with 95% confidence intervals (CI) were calculated for theoutcome of macrosomia (birthweight 4000g), as a function of acategorical change in pregnancy BMI: BMI loss (BMI change-0.5),no change (-0.5 to 0.5), minimal (0.6 to 5), moderate (5.1 to 10), andexcessive (10). No change in BMI served as the reference group. Theimpact of pregnancy change in BMI was determined for the entirecohort and then stratified by prepregnancy WHO BMI category.RESULTS: The study population consisted of 436,414 womenwith sin-gleton gestations. Overall, women with moderate and excessive BMIchanges had an aOR of 1.66 (95% CI1.50-1.83) and 3.18 (95%CI2.86-3.55), respectively for fetal macrosomia, when compared towomen with no BMI change. When stratified by prepregnancy BMI,normal (aOR5.29, 95% CI3.59-7.81) and overweight women(aOR5.29, 95%CI4.17-6.72)with a BMI change10 had a higherodds of macrosomia as compared to any of the three obese classes:class I (aOR4.08, 95% CI3.25-5.12), class II (aOR3.72, 95%CI2.77-5.00), class II (aOR2.39, 95% CI1.72-3.31).CONCLUSION: Excessive change in pregnancy BMI results in an in-creased odds of macrosomia. Women at highest risk for developingfetal macrosomia were those who had a normal or overweightprepregnancy BMI, who then underwent excessive BMI change dur-ing pregnancy.</p><p>Unadjusted incidence of birthweight &gt;4000 g as afunction of change in pregnancy body mass index</p><p>Poster Session III Doppler Assess, Fetus, Prematurity, U/S, Med-Surg-Diseases www.AJOG.org</p><p>S190 American Journal of Obstetrics&amp; Gynecology Supplement to JANUARY 2013</p></li></ul>


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