Obesity In Pregnancy Research Articles

Measurements of HbA1c, and fasting plasma glucose in patients with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a heterogeneous disease that is characterized by a combination of signs and symptoms of androgen excess (hirsutism and/or hyperandrogenemia) and ovarian dysfunction (oligo ovulation and/or polycystic ovarian morphology (PCOM)), provided that other specific diagnoses have been excluded.The main features of PCOS include reduced fertility due to dysfunctional follicular maturation and ovulation, disturbance of reproductive hormones including luteinizing hormone (LH) hypersecretion, and hyperandrogenism which causes acne and hirsutism. Insulin resistance and compensatory hyperinsulinism have been demonstrated to be related to androgen excess in PCOS, as according to many studies, insulin acts as a co gonadotropin on the ovaries, facilitate androgen secretion from the adrenal glands and modulate luteinizing hormone pulsatility.Insulin resistance is considered a major risk factor for the development of type 2 diabetes mellitus in PCOS. Patients with PCOS are predisposed to consequences of IR such as: central obesity, acanthosis nigricans, hirsutism, and early pregnancy loss.So, screening of all PCOS women for T2DM and prediabetes is mandatory.

Associations of maternal metabolic profile with placental and fetal cerebral and cardiac hemodynamics

ObjectiveMaternal obesity and metabolic health affect pregnancy outcomes. We examined whether maternal metabolic profiles are associated with placental and fetal hemodynamics. Study DesignIn a population-based prospective cohort study among 1175 women we examined the associations of an adverse maternal metabolic profile in early pregnancy with placental, fetal cerebral and cardiac hemodynamic development. We obtained maternal pre-pregnancy BMI by questionnaire and measured blood pressure, cholesterol, triglycerides and glucose concentrations at a median gestational age of 12.6 (95 % range 9.6–17.1) weeks. An adverse maternal metabolic profile was defined as ≥4 risk factors. Placental and fetal hemodynamics were measured by pulsed-wave-Doppler at a median gestational age of 30.3 (95 % range 28.8–32.3) weeks. ResultsAn adverse maternal metabolic profile was associated with a 0.29 Z-score higher (95 %CI 0.08−0.50) fetal cerebral middle artery pulsatility index (PI), but not with placental or fetal cardiac hemodynamic patterns. When the individual components of an adverse maternal metabolic profile were assessed, we observed that higher maternal total cholesterol and triglyceride concentrations were associated with a higher cerebral middle artery PI (Z-score, 0.09 (95 %CI 0.02−0.15), 0.09 (95 %CI 0.03−0.15) per Z-score increase). Higher total and HDL maternal cholesterol concentrations were also associated with a higher aorta ascendens peak systolic velocity (PSV) Z-score, 0.08 (95 %CI 0.01−0.14)), and a larger left cardiac output (Z-score, 0.08 (95 %CI 0.00−0.15), respectively). ConclusionAn adverse maternal metabolic profile, especially higher cholesterol and triglycerides concentrations, are associated with increased fetal cerebral vascular resistance and larger fetal aorta ascendens diameter, PSV and left cardiac output, but not with placental vascular resistance indices. Further studies are needed to identify long-term consequences of the observed associations.

Impact of Sugary Food Consumption on Pregnancy: A Review.

Obesity in pregnancy has been directly associated with an increased risk of almost all pregnancy complications such as gestational hypertension, preeclampsia, gestational diabetes mellitus (GDM), and premature delivery. Thereby, according to current evidence available, life-style interventions to prevent pre-pregnancy overweight and obesity in women of fertile age are necessary to reduce the negative impact of obesity on mother and child health. Unhealthy dietary patterns, together with the increased consumption of processed foods rich in simple sugar and sweeteners are some of the responsible, among others, for the increase in obesity rates during the last years. Nevertheless, how its consumption can affect pregnancy outcomes and long-term children’s health is still uncertain. This review aims to collate the available evidence about the consequences of unhealthy dietary patterns and sugary products consumption, including sweeteners, during pregnancy for obesity in childhood and mid-childhood. High simple sugar intake during gestation may contribute to an excessive gestational weight gain (GWG) as well as to develop other pregnancy complications such as GDM, preeclampsia and preterm birth. The heterogeneity of study populations, sample size, different approaches to measure GWG, GMD, preeclampsia, and birth weight, among other conditions, might explain the divergences observed among studies. Therefore, large, well-designed intervention-controlled trials with biological biomarkers to ensure dietary adherence are necessary to evaluate the effectiveness of lifestyle interventions in order to provide effective nutritional advice.

Iron-Dependent Apoptosis Causes Embryotoxicity in Inflamed and Obese Pregnancy

Since iron is essential for pregnancy, iron supplements are routinely prescribed to pregnant women without screening for iron deficiency. Most women in developed countries have sufficient iron stores, prompting concerns of the potential risks of iron supplementation in iron-replete women. A signal of potential harm of this practice is the association of maternal iron marker ferritin and pregnancy complications. Since ferritin is also induced by inflammation, it is unclear whether iron excess, inflammation, or their interaction cause fetal injury. We used mouse models to address this question. Two mouse models of maternal iron excess were used and compared to mice with normal iron status. To model dietary iron supplementation, C57BL/6 females were fed high-iron diet (2500-5000ppm iron) for 1 week prior to and during pregnancy. To model genetic iron loading, hepcidin knockout females were used and fed standard chow (185ppm iron). Two models of maternal inflammation were used. Acute systemic maternal inflammation was induced by a single subcutaneous injection of LPS on E8.5 or 15.5. Obesity was used as a model of mild chronic systemic maternal inflammation and was induced by feeding female mice Western diet. We evaluated the maternal, placental, and embryo response to iron excess in LPS- and obesity-induced inflammation at various time points. In the model of acute inflammation, we observed an adverse synergistic effect on embryo development when dams were both iron-loaded and LPS-injected, but not with either condition alone. On E8.5, LPS injection in iron-loaded dams caused embryo loss and encephalic malformations (Fig 1a) and on E15.5, LPS injection in iron-loaded dams caused embryo demise and resorption (Fig 1b). Western blotting and immunostaining showed increased apoptotic marker cleaved caspase-3 protein localized to endothelia in placentas and embryos, only when the dam was both iron-loaded and LPS-injected. Cytokine screen in vitro identified TNFα as the signal that synergized with iron to potentiate apoptosis of endothelial cells. Treatment of iron-loaded dams with TNFα-neutralizing antibody protected embryos from LPS-induced death, demonstrating the embryotoxic role of maternal TNFα in iron-loaded dams. Furthermore, RNA-Seq analysis of placental endothelial cells showed enrichment in oxidative stress pathways with maternal iron loading. Treatment of iron-loaded dams with antioxidant α-tocopherol protected against LPS-induced embryo death, attenuated placental inflammation and cleaved caspase-3 expression, and prevented endothelial apoptosis in the placenta and embryo. These data show that iron loading causes endothelial oxidative stress, which sensitizes endothelial cells to inflammation-induced apoptosis. In the obesity model, iron loading worsened embryotoxicity, causing subcutaneous hemorrhaging and eye malformations (Fig 1c), and potentiated placental cleaved caspase-3 expression. Iron loading increased TNFα levels in maternal serum. Importantly, treatment of obese iron-loaded dams with neutralizing TNFα antibody throughout pregnancy reduced the incidence of embryo eye malformations, confirming the role of TNFα in causing embryo injury in iron-loaded obese pregnancy. In summary, maternal iron excess worsened inflammation-induced embryo injury. Iron-dependent embryotoxicity was mediated by TNFα causing lethal apoptotic damage to embryo and placental endothelium which was prevented by antioxidant therapy. Our models raise the possibility that women exposed to both excessive iron and inflammation could be at risk for preventable pregnancy complications. Figure 1. Embryo outcomes in mouse pregnancies with maternal iron loading and inflammation. Figure 1 Disclosures Ganz: Akebia: Consultancy; Vifor: Consultancy; Ionis Pharmaceuticals: Consultancy; Silarus Therapeutics: Current equity holder in private company; Intrinsic LifeSciences: Current equity holder in private company; Global Blood Therapeutics: Consultancy; Ambys: Consultancy; Gossamer Bio: Consultancy; Astellas: Consultancy; Rockwell: Consultancy; Sierra Oncology: Consultancy; Disc Medicine: Consultancy; American Regent: Consultancy. Nemeth:Intrinsic LifeSciences: Current equity holder in private company; Vifor: Consultancy; Protagonist: Consultancy; Silarus Therapeutics: Current equity holder in private company; Ionis Pharmaceuticals: Consultancy.

The role of obesity and gestational diabetes on placental size and fetal oxygenation

IntroductionMaternal pregestational obesity is a significant risk factor for adverse pregnancy outcomes, such as gestational diabetes. Both these conditions can have an impact on placental development and affect maternal-fetal exchanges, compromising fetal metabolic status. The aim of the study is to investigate the influence of pre-pregnancy BMI on placental size and to evaluate the role of obesity and gestational diabetes mellitus (GDM) on fetal oxygenation in overweight and obese pregnant women. Methods208 normal weight (NW), 57 overweight (OW) and 69 obese (OB) women were studied at elective cesarean section (CS) at term. 10 OW and 24 OB women were affected by GDM. Maternal, fetal and placental data were collected. Respiratory gases and acid-base balance were measured in umbilical venous and arterial blood. ResultsPlacental weight and thickness were higher in OB pregnancies. Lower fetal-placental ratios (F/P) were found in GDM pregnancies, both OW and OB. Fetuses from OB mothers were more hypoxic and acidemic compared to NW, particularly when complicated by GDM. DiscussionIn agreement with previous studies, our data show that placentas from OB and GDM pregnancies are heavier and thicker, suggesting that an unbalanced pregestational nutritional status can decrease the placental efficiency in maternal-fetal exchanges. Fetuses from obese women are also hypoxic and acidemic, while fetuses from gestational diabetic mothers are hypoxic, reflecting that an altered pre-pregnancy BMI can affect fetal oxygenation, and GDM can play an additional detrimental role, thus worsening placental function and fetal oxygenation.

Supplementation with a prebiotic (polydextrose) in obese mouse pregnancy improves maternal glucose homeostasis and protects against offspring obesity.

We hypothesised that maternal diet-induced-obesity has adverse consequences for offspring energy expenditure and susceptibility to obesity in adulthood, and that the prebiotic polydextrose (PDX) would prevent the consequences of programming by maternal obesity. Female mice were fed a control (Con) or obesogenic diet (Ob) for 6 weeks prior to mating and throughout pregnancy and lactation. Half the obese dams were supplemented with 5% PDX (ObPDX) in drinking water throughout pregnancy and lactation. Offspring were weaned onto standard chow. At 3 and 6 months, offspring energy intake (EI) and energy expenditure (EE by indirect calorimetry) were measured, and a glucose-tolerance test performed. Offspring of control (OffCon), obese (OffOb) and PDX supplemented (OffObP) dams were subsequently challenged for 3 weeks with Ob, and energy balanced reassessed. Potential modifiers of offspring energy balance including gut microbiota and biomarkers of mitochondrial activity were also evaluated. Six-month-old male OffOb demonstrated increased bodyweight (BW, P < 0.001) and white adipose tissue mass (P < 0.05), decreased brown adipose tissue mass (BAT, P < 0.01), lower night-time EE (P < 0.001) versus OffCon, which were prevented in OffObP. Both male and female OffOb showed abnormal glucose-tolerance test (peak [Glucose] P < 0.001; AUC, P < 0.05) which was prevented by PDX. The Ob challenge resulted in greater BW gain in both male and female OffOb versus OffCon (P < 0.05), also associated with increased EI (P < 0.05) and reduced EE in females (P < 0.01). OffObP were protected from accelerated BW gain on the OB diet compared with controls, associated with increased night-time EE in both male (P < 0.05) and female OffObP (P < 0.001). PDX also prevented an increase in skeletal muscle mtDNA copy number in OffOb versus OffCon (P < 0.01) and increased the percentage of Bacteroides cells in faecal samples from male OffObP relative to controls. Maternal obesity adversely influences adult offspring energy balance and propensity for obesity, which is ameliorated by maternal PDX treatment with associated changes in gut microbiota composition and skeletal muscle mitochondrial function.

The Impact of Maternal Body Composition and Dietary Fat Consumption upon Placental Lipid Processing and Offspring Metabolic Health.

The proportion of women of reproductive age who are overweight or obese is increasing globally. Gestational obesity is strongly associated in both human studies and animal models with early-onset development of adult-associated metabolic diseases including metabolic syndrome in the exposed offspring. However, animal model studies have suggested that gestational diet in obese pregnancies is an independent but underappreciated mediator of offspring risk for later life metabolic disease, and human diet consumption data have highlighted that many women do not follow nutritional guidelines prior to and during pregnancy. Thus, this review will highlight how maternal diet independent from maternal body composition impacts the risk for later-life metabolic disease in obesity-exposed offspring. A poor maternal diet, in combination with the obese metabolic state, are understood to facilitate pathological in utero programming, specifically through changes in lipid handling processes in the villous trophoblast layer of the placenta that promote an environment associated with the development of metabolic disease in the offspring. This review will additionally highlight how maternal obesity modulates villous trophoblast lipid processing functions including fatty acid transport, esterification and beta-oxidation. Further, this review will discuss how altering maternal gestational diet may ameliorate these functional changes in lipid metabolic processes in the obese placenta.

Predictors of patterns of weight change 1 year after delivery in a cohort of Mexican women.

To evaluate the associations of pregestational BMI, gestational weight gain (GWG) and breast-feeding at 1 month postpartum with four patterns of weight change during the first year after delivery: postpartum weight retention (PPWR), postpartum weight gain (PPWG), postpartum weight retention + gain (PPWR + WG) and return to pregestational weight. In this secondary analysis of a prospective study, we categorised postpartum weight change into four patterns using pregestational weight and weights at 1, 6 and 12 months postpartum. We evaluated their associations with pregestational BMI, GWG and breast-feeding using multinomial logistic regression. Results are presented as relative risk ratios (RRR) and 95 % CI. Mexico City. Women participating in the Programming Research in Obesity, Growth, Environment and Social Stressors pregnancy cohort. Five hundred women were included (53 % of the cohort). Most women returned to their pregestational weight by 1 year postpartum (57 %); 8 % experienced PPWR, 14 % PPWG and 21 % PPWR + WG. Compared with normal weight, pregestational overweight (RRR 2·5, 95 % CI 1·3, 4·8) and obesity (RRR 2·2, 95 % CI 1·0, 4·7) were associated with a higher risk of PPWG. Exclusive breast-feeding, compared with no breast-feeding, was associated with a lower risk of PPWR (RRR 0·3, 95 % CI 0·1, 0·9). Excessive GWG, compared with adequate, was associated with a higher risk of PPWR (RRR 3·3, 95 % CI 1·6, 6·9) and PPWR + WG (RRR 2·4, 95 % CI 1·4, 4·2). Targeting women with pregestational overweight or obesity and excessive GWG, as well as promoting breast-feeding, may impact the pattern of weight change after delivery and long-term women's health.

Maternal Obesity Does Not Exacerbate the Effects of LPS Injection on Pregnancy Outcomes in Mice.

Simple SummaryObesity increases the risk of problems during pregnancy, potentially due to inappropriate activation of the immune system. We predicted that, because of this immune activation, obesity in mice would exacerbate the effects of lipopolysaccharide (LPS), a substance that mimics infection, impairs fetal growth and leads to pregnancy loss in animal models. Mice were fed a high- or low-fat diet for thirteen weeks prior to mating, and then received an LPS or control injection during pregnancy. Treatment with LPS induced pregnancy loss in some mice, as expected. However, LPS did not have more severe effects in females fed the high-fat diet, who were heavier. Our results therefore do not support the hypothesis that an otherwise healthy obese pregnancy can be driven to an adverse outcome by a low-level infection. Our study improves the understanding of why obese women are at greater risk of adverse pregnancy outcomes. In doing so, it will contribute to future studies that seek to determine how obese pregnancies at risk of adverse outcomes can be distinguished from healthy obese pregnancies.Obesity increases the risk of a number of pregnancy complications, potentially due to chronic inflammation. We predicted that an obesogenic high-fat diet (HFD) in mice would create an inflammatory environment that would exacerbate the effects of lipopolysaccharide (LPS), an inflammatory insult, administered during pregnancy. Females were placed on a HFD or a low-fat diet (LFD) prior to mating, injected with 2 µg LPS or control on gestational day 7 and collected on day 14. Treatment with LPS increased the odds that a female thought to be pregnant at injection had no conceptuses at day 14 (p = 0.024), suggesting that injection with LPS was more likely to induce complete abortion. However, there was no effect of diet on the odds of having no conceptuses at day 14 and no interaction between diet and LPS injection. Diet and LPS injection had no effect on the number of viable fetuses in females still pregnant at day 14. For fetal weight, there was a significant interaction between diet and treatment (p = 0.017), whereby LPS reduced fetal weight in HFD females but not in LFD females. However, LPS treatment of HFD females reduced fetal weight to that observed in control-injected LFD females. Although LPS increased the odds of abortion, there was little evidence that a HFD exacerbated the effects of LPS.

Maternal obesity causes fetal hypothalamic insulin resistance and disrupts development of hypothalamic feeding pathways

ObjectivePerinatal exposure to maternal obesity results in predisposition of offspring to develop obesity later in life. Increased weight gain in offspring exposed to maternal obesity is usually associated with hyperphagia, implicating altered central regulation of food intake as a cause. We aimed to define how maternal obesity impacts early development of the hypothalamus to program lasting dysfunction in feeding regulatory pathways. MethodsMice offspring of diet-induced obese mothers were compared to the offspring of lean control mothers. We analysed gene expression in the fetal hypothalamus, alongside neurosphere assays to investigate the effects of maternal obesity on neural progenitor cell proliferation in vitro. Western blotting was used to investigate the insulin signalling pathway in the fetal hypothalamus. Characterisation of cell type and neuropeptide profile in adulthood was linked with analyses of feeding behaviour. ResultsThere was a reduction in the expression of proliferative genes in the fetal hypothalamus of offspring exposed to maternal obesity. This reduction in proliferation was maintained in vitro when hypothalamic neural progenitor cells were grown as neurospheres. Hypothalamic fetal gene expression and neurosphere growth correlated with maternal body weight and insulin levels. Foetuses of obese mothers showed hypothalamic insulin resistance, which may be causative of reduced proliferation. Furthermore, maternal obesity activated the Notch signalling pathway in neonatal offspring hypothalamus, resulting in decreased neurogenesis. Adult offspring of obese mothers displayed an altered ratio of anorexigenic and orexigenic signals in the arcuate nucleus, associated with an inability to maintain energy homeostasis when metabolically challenged. ConclusionsThese findings show that maternal obesity alters the molecular signature in the developing hypothalamus, which is associated with disrupted growth and development of hypothalamic precursor cells and defective feeding regulation in adulthood. This is the first report of fetal hypothalamic insulin resistance in an obese pregnancy and suggests a mechanism by which maternal obesity causes permanent changes to hypothalamic structure and function.

Placental Adaptive Changes to Protect Function and Decrease Oxidative Damage in Metabolically Healthy Maternal Obesity.

Pregnancy-related disorders, including preeclampsia and gestational diabetes, are characterized by the presence of an adverse intrauterine milieu that may ultimately result in oxidative and nitrosative stress. This scenario may trigger uncontrolled production of reactive oxygen species (ROS) such as superoxide anion (O●−) and reactive nitrogen species (RNS) such as nitric oxide (NO), along with an inactivation of antioxidant systems, which are associated with the occurrence of relevant changes in placental function through recognized redox post-translational modifications in key proteins. The general objective of this study was to assess the impact of a maternal obesogenic enviroment on the regulation of the placental nitroso-redox balance at the end of pregnancy. We measured oxidative damage markers—thiobarbituric acid-reacting substances (TBARS) and carbonyl groups (C=O) levels; nitrosative stress markers—inducible nitric oxide synthase, nitrosothiol groups, and nitrotyrosine residues levels; and the antioxidant biomarkers—catalase and superoxide dismutase (SOD) activity and expression, and total antioxidant capacity (TAC), in full-term placental villous from both pre-pregnancy normal weight and obese women, and with absence of metabolic complications throughout gestation. The results showed a decrease in C=O and TBARS levels in obese pregnancies. Although total SOD and catalase concentrations were shown to be increased, both activities were significantly downregulated in obese pregnancies, along with total antioxidant capacity. Inducible nitric oxide sintase levels were increased in the obese group compared to the lean group, accompanied by an increase in nitrotyrosine residues levels and lower levels of nitrosothiol groups in proteins such as ERK1/2. These findings reveal a reduction in oxidative damage, accompanied by a decline in antioxidant response, and an increase via NO-mediated nitrative stress in placental tissue from metabolically healthy pregnancies with obesity. All this plausibly points to a placental adaptation of the affected antioxidant response towards a NO-induced alternative pathway, through changes in the ROS/RNS balance, in order to reduce oxidative damage and preserve placental function in pregnancy.

Association between change in maternal physical activity during pregnancy and infant size, in a sample overweight or obese women

ABSTRACT Physical activity (PA) naturally declines during pregnancy and its effects on infant size are unclear, especially in overweight or obese pregnancies, a low-active subpopulation that tends deliver heavier infants. The objective of this study was to evaluate changes in prenatal PA and infant birthweight in a group of overweight or obese pregnant women. We employed a prospective analysis using data from a randomized controlled exercise trial (2001 to 2006) in sedentary, overweight or obese pregnant women in Michigan. Women with complete data on peak oxygen consumption, daily PA (via pedometers) and birthweight were included in the analyses. Change in PA was estimated via repeated measures analyses, and then its influence on infant birthweight was assessed via linear regression. Eighty-nine pregnant women were included and considered low-active (6,579.91 ± 2379.17 steps/day). PA declined from months 4 to 8 (−399.73 ± 371.38 steps∙day−1∙month−1). Analyses showed that the decline in PA (β = −0.28 g, 95%CI: −0.70, 0.25 g, p = .35) was not associated with birthweight. The findings of this study demonstrated that the decline in maternal PA during mid- to late-pregnancy, in overweight or obese women, was unrelated to infant birthweight. Future investigations should employ rigorous measurements of PA and infant anthropometry in this subpopulation.

Administration of recombinant human placental growth factor decreases blood pressure in obese hypertensive pregnant rats.

Although epidemiological studies have shown that obesity is associated with increased incidence of hypertension during pregnancy, the mechanisms linking these two comorbidities are not as well studied. Previous investigations detected lower levels of the anti-hypertensive and pregnancy-related factor, placental growth factor (PlGF), in obese hypertensive pregnancies. Therefore, we examined whether obese hypertensive pregnant rats have reduced PlGF and whether increasing its levels by administering recombinant human (rh)PlGF reduces their blood pressure. We utilized a genetic model of obesity characterized to be heavier, hypertensive and fertile, namely rats having heterozygous deficiency of the melanocortin-4 receptor (MC4R-def). MC4R-def obese rats had lower circulating levels of PlGF than wild-type lean controls at gestational day 19. Also, assessment of the PlGF receptor, Flt-1, in the vasculature showed that its levels were reduced in aorta and kidney glomeruli but increased in small mesenteric arteries. Chronic intraperitoneal administration of rhPlGF from gestational day 13-19 significantly increased circulating PlGF levels in both obese and lean rats, but reduced blood pressure only in the obese pregnant group. The rhPlGF treatment did not alter maternal body and fat masses or circulating levels of the adipokines, leptin and adiponectin. In addition, this treatment did not impact average foetal weights but increased placental weights regardless of obese or lean pregnancy. PlGF is reduced in MC4R-def obese hypertensive pregnant rats, which is similar to findings in obese hypertensive pregnant women, while increasing its levels with exogenous rhPlGF reduces their blood pressure.

Obesity represents a strong pathogenetic link with the pathology of pregnancy and childbirth

Obesity is a significant health and social problem that is the scale of the growing worldwide epidemic. Over the past 10 years, the number of obese pregnant women has doubled. There are multiple risk factors associated with obesity, which includes poor nutrition, foods that are high in easily digestible carbohydrates and fats, frequent snacks, and widespread fast food consumption. Metabolic changes, especially in women with the genetic predisposition, are manifested by insulin resistance, hyperinsulinemia, arterial hypertension, and hypercoagulation syndrome. The course of pregnancy and childbirth in obese women is associated with a series of successive pathological conditions, such as miscarriage, the occurrence of gestational diabetes mellitus, preeclampsia and eclampsia, infectious complications, prolonged pregnancy, the occurrence of bleeding and much more. We have analyzed modern ideas about womens reproductive health and the course of pregnancy and childbirth in obesity.

1371-P: Effect of Omega-3 Supplementation in Pregnant Women with Obesity on Offspring Growth and Body Composition

Background: Maternal obesity is a growing health burden associated with adverse cardiometabolic health outcomes in the offspring. Higher omega-3 polyunsaturated fatty acids (n3 PUFA) status in pregnancy is associated with higher birthweight. However, the effect of n3 supplementation, specifically in pregnant women with overweight and obesity, on fetal growth and adiposity has not been explored. Objective: To examine the effect of n-3 supplementation in overweight and obese pregnancy on offspring anthropometry and body composition. Methods: A secondary analysis of a double-blind randomized controlled trial of pregnant women with pre-pregnancy BMI≥ 25 randomized to daily DHA plus EPA (2 g/d) or placebo (wheat germ oil) from 10-16 weeks gestation to delivery. We compared the following newborn outcomes i) birthweight z-score derived from anthropometrics, ii) % adiposity, fat-mass and fat-free mass using PeaPodTM and skin fold thickness measurement, by randomization group using Student T-test and Wilcoxon rank-sum for bivariate analyses, and linear regression adjusting for gestational age (GA) and sex. Results: For the 46 mother-child dyads with complete exposure and outcome data, median (IQR) maternal BMI was 30.2 (27.9, 35.5) kg/m2. Gestation was longer in the treatment vs. placebo group (40 (38.6,40.1) vs. 38.9 (38.0,39.4) weeks, p=0.009). Sex- and GA- specific birthweight z-score (-0.2 ± 0.7 vs. -0.6 ± 0.6-unit, p =0.035), but not birth length z-score (-0.3 ± 0.7 vs. -0.6 ± 0.6-unit, p =0.21), was higher in the treatment vs. placebo group. N-3 treatment was associated with higher fat-free mass (β 131.4g higher for treatment vs. control, 95% CI 3.1, 259.7) by skinfolds but not %bodyfat or fat mass at birth. Conclusion: n-3 supplementation early in pregnancy in women with obesity increased birthweight, but this results from increased fetal lean mass accrual. Future investigations should explore the long-term impact of this intervention on offspring cardiometabolic health. Disclosure C. Monthe-Dreze: None. S. Enstad: None. S. Sen: None. S. Hauguel de Mouzon: None. P. Catalano: None. Funding National Institutes of Health (RHD057236); Case Western Reserve University/Cleveland Clinic Clinical and Translational Science Award (UL1RR024989)

Telehealth in pregnancy

Telehealth in pregnancy

Effects of Maternal Obesity On Placental Phenotype.

The incidence of obesity is rising rapidly worldwide with the consequence that more women are entering pregnancy overweight or obese. This leads to an increased incidence of clinical complications during pregnancy and of poor obstetric outcomes. The offspring of obese pregnancies are often macrosomic at birth although there is also a subset of the progeny that are growth-restricted at term. Maternal obesity during pregnancy is also associated with cardiovascular, metabolic and endocrine dysfunction in the offspring later in life. As the interface between the mother and fetus, the placenta has a central role in programming intrauterine development and is known to adapt its phenotype in response to environmental conditions such as maternal undernutrition and hypoxia. However, less is known about placental function in the abnormal metabolic and endocrine environment associated with maternal obesity during pregnancy. This review discusses the placental consequences of maternal obesity induced either naturally or experimentally by increasing maternal nutritional intake and/or changing the dietary composition. It takes a comparative, multi-species approach and focusses on placental size, morphology, nutrient transport, metabolism and endocrine function during the later stages of obese pregnancy. It also examines the interventions that have been made during pregnancy in an attempt to alleviate the more adverse impacts of maternal obesity on placental phenotype. The review highlights the potential role of adaptations in placental phenotype as a contributory factor to the pregnancy complications and changes in fetal growth and development that are associated with maternal obesity.

English

Pre-eclampsia/Eclampsia has significant impact on maternal and perinatal health. Little is known about prevalence and risk factors for pre-eclampsia/eclampsia in Tanzania. This study aimed to determine prevalence and risk factors for pre-eclampsia/eclampsia among women who delivered at KCMC&nbsp; hospital between 2000 and 2014. Retrospective cross-sectional study was conducted at KCMC medical birth registry. Multivariable logistic regression models were performed to obtain odds ratios with 95% CI for factors associated with pre/eclampsia. P-value&lt;0.05 was considered statistically significant. A total of 40,176 mothers were analysed. The prevalence of pre/eclampsia was 4.2%. Factors&nbsp; such as maternal age (&ge;35) years (AOR = 1.73), &ge;12 years of schooling (AOR=1.29), being unmarried (AOR=2.03), overweight (AOR=1.99), obesity (AOR=5.52),&nbsp; hypertension (AOR=18.66), anaemia (AOR=3.53), and multiple pregnancy (AOR=6.58), &nbsp;were&nbsp; associated with higher risk of pre-eclampsia/eclampsia &nbsp;while ANC visits (&ge;4) reduced the risk of pre-eclampsia (AOR= 0.78). This study provides an estimate of prevalence of pre-eclampsia at KCMC hospital in Northern Tanzania. Factors such as advanced maternal age (&ge;35 years), &ge;12 years of schooling, being unmarried, overweight, obesity, hypertension, anaemia and multiple pregnancy were associated with higher risk of pre-eclampsia while having &ge;4 ANC visits reduced the risk of pre-eclampsia at KCMC.&nbsp; Key words: Prevalence, pre-eclampsia, eclampsia, risk factors, Tanzania. &nbsp

Endothelial Mineralocorticoid Receptor Deletion Abrogates Leptin‐Induced Endothelial Dysfunction in Pregnant Mice

Obesity is a risk factor for endothelial dysfunction and hypertension in pregnancy, both of which are hallmarks of preeclampsia. Our lab has demonstrated that obesity‐associated endothelial dysfunction and hypertension in female mouse models is mediated via leptin‐induced aldosterone production and subsequent mineralocorticoid receptor (MR) activation. We also showed that progesterone increases endothelial MR (ECMR) expression and that high progesterone levels in pregnant mice are associated with highly elevated ECMR expression, potentially rendering pregnant female mice susceptible to leptin‐induced endothelial dysfunction in obese pregnancy. Therefore, we hypothesized that ECMR deletion would prevent leptin‐induced endothelial dysfunction in pregnant mice in late gestation. Endothelial function was experimentally measured by wire myography concentration response curves to acetylcholine in mouse aorta. Chronic leptin infusion (0.9mg/kg/day, s.c. osmotic minipump) throughout late‐gestation (gestational days 11–18) induced endothelial impairment in wild‐type pregnant mice that was impaired both compared to sham‐treated pregnant (2‐way ANOVA with repeated measures, *P&lt;0.05) and non‐pregnant leptin‐infused females (*P&lt;0.05). However, leptin infusion in pregnant ECMR−/− mice did not induce similar endothelial dysfunction (*P&lt;0.05). Relaxation responses to acetylcholine in the presence of LNAME indicated that endothelial dysfunction in pregnant leptin‐infused mice was attributable to reduction in nitric oxide activity. In addition, no changes in endothelial‐independent sodium nitroprusside responses were observed among groups. Placental dysfunction is a characteristic of preeclampsia that precludes the development of endothelial dysfunction and hypertension. In homogenized placentas, mRNA expression of hypoxia‐inducible factor 1α (HIF1α), a marker of ischemia, was increased by leptin infusion in wild‐type (1.9±0.2‐fold change from sham wild‐type, P=0.08), but not in ECMR−/− (1.2±0.2‐fold change from sham ECMR−/−) pregnant mice. These changes in placental function were associated with adverse fetal effects in leptin‐infused wild‐type mice as indicated by decreased pup weight (0.86±0.04g sham wild‐type vs 0.52±0.11g wild‐type +leptin, *P&lt;0.05). However, ECMR deletion rescued pup weight in leptin‐infused pregnant mice (0.79±0.08g, sham ECMR−/− vs 0.86±0.11g, ECMR−/− +leptin). Collectively, these data indicate that high leptin levels in obese pregnancies may predispose to placental dysfunction and endothelial dysfunction, which are characteristics of preeclampsia.Support or Funding Information1R01HL130301‐01, 19EIA34760167, Adrenal Center pilot grant, 1K99HL146948‐01A1

Perceptions of risk and influences of choice in pregnant women with obesity. An evidence synthesis of qualitative research.

Between 7-35% of the maternity population are obese in high income countries and 1-40% in lower or middle-income countries. Women with obesity are traditionally limited by the choices available to them during pregnancy and birth because of the higher risk of complications. This evidence synthesis set out to summarise how women with obesity's perceptions of pregnancy and birth risk influence the care choices that they make. A search of medical and health databases for qualitative studies written in the English language, published Jan 1993-April 2019 and reporting on pregnant women with obesity's perception of risk and influence of pregnancy and birth choices. Data was extracted by two reviewers onto a questions framework and then analysed using a thematic synthesis technique. Confidence in the qualitative findings was assessed using GRADE-CERQual. 23 full texts were included. The common themes on perception of risk were: 'Self-blame arising from others' stereotyped beliefs ', 'Normalisation', 'Lack of preparation', 'Fearful acceptance and inevitability' and 'Baby prioritised over mother'. For influence of choices, the themes were: 'External influences from personal stresses', 'Restrictive guidelines', 'Relationship with healthcare professional' and 'Perception of Risk'. Evidence on what influences women with obesity's pregnancy choices is limited. Further research is needed on the best methods to discuss the risks of pregnancy and birth for women with obesity in a sensitive and acceptable manner and to identify the key influences when women with obesity make choices antenatally and for birth planning.