Pregnancy Outcomes In Obese Women Research Articles

Reversal of maternal obesity attenuates hypoxia and improves placental development in the preeclamptic-like BPH/5 mouse model.

Women with obesity have higher risk of adverse pregnancy outcomes, including preeclampsia (PE). Late-gestational hypertension, aberrant fetoplacental development, and fetal growth restriction (FGR), hallmarks of PE, are observed spontaneously in BPH/5 mice. Similar to obese preeclamptic women, BPH/5 mice have higher visceral white adipose tissue (WAT) and circulating leptin. We hypothesized that attenuation of maternal obesity and serum leptin in pregnant BPH/5 mice will improve fetoplacental development by decreasing hypoxia markers and leptin expression at the maternal-fetal interface. To test this hypothesis, BPH/5 mice were fed ad libitum (lib) and pair-fed (PF) to C57 ad lib controls beginning at embryonic day (e) 0.5. Hypoxia-related genes, hypoxia inducible factor (Hif) 1α, stem cell factor (Scf), heme oxygenase-1 (Ho-1), leptin (Lep), and leptin receptor (LepR) were assessed in e7.5 implantation sites. BPH/5 ad lib had 1.5 to 2-fold increase in Hif1α, Scf, and Ho-1 mRNA and a greater than 3-fold increase in leptin mRNA vs. C57 that was attenuated with PF. Exogenous leptin promoted Hif1α and Ho-1 mRNA expression in e7.5 decidua in vitro. While hypoxic conditions in vitro did not change decidual leptin mRNA. Furthermore, BPH/5 PF mice demonstrated improved fetal and placental outcomes later in gestation, with greater placental vascular area by e18.5 and attenuation of FGR. In conclusion, pair-feeding BPH/5 mice beginning at conception may improve placental vasculature formation via decreased leptin and hypoxia-associated markers in this model. Future investigations are needed to better determine the effect of hypoxia and leptin on pregnancy outcomes in obese pregnant women.

P-596 Comparative efficacy of Letrozole (5 mg) versus Clomiphene citrate (100 mg) for ovulation induction among infertile women

Abstract Study question Does Letrozole have better offerings while being compared to Clomiphene citrate as an Ovulation inducing agent in infertile women? Summary answer Compared to clomiphene, Letrozole - an aromatase inhibitor, is associated with higher live-birth and ovulation rates among infertile women. What is known already Anovulatory dysfunction is a common problem and is responsible for about 40% of female infertility and among causes; PCOS (polycystic ovarian syndrome) is the leading cause. Clomiphene citrate has been traditionally used as the drug of choice for treatment of women with anovulatory infertility. In the last decade, an aromatase inhibitor, letrozole, has emerged as an alternative ovulation induction agent among anovulatory women with polycystic ovarian syndrome. Letrozole has a definitive role in anovulatory women who have not responded to clomiphene citrate therapy, as confirmed by literature. Study design, size, duration Randomized double-blind study. Total 100 women were randomly assigned and divided into 2 groups of 50 patients each. The 2 groups were well matched at baseline. Study participants are of age 20 to 39 years. Study began in October 2019 and was completed in October 2021. Participants/materials, setting, methods Group 1: Clomiphene citrate (100 mg daily) and group 2: letrozole (5 mg daily), started from any day between 3-5 of the menstrual cycle and continued up to 5 consecutive days. Both groups have received Estradiol Valerate 4 mg on the 12th day of menstruation until 16th day of menstruation. All patients had USG monitoring of follicular and endometrium size with perifollicular flow and uterine scoring system for reproduction (USSR) score with timed intercourse. Main results and the role of chance Women who received letrozole as compared to those who received clomiphene citrate had more cumulative live births (36 of 50 [72%] vs. 28 of 50 [56%]). Number of women ovulated in Letrozole group was – 42 (84%) while in Clomiphene citrate (CC) Group it was 39 (78%). The ovulation rate was significantly higher with letrozole than with clomiphene citrate. Among the study participants who ovulated, there was a significantly greater chance of singleton pregnancy with letrozole compared to clomiphene citrate. The mean number of dominant follicles (18 mm) was 1.40 ± 0.58 for letrozole and 1.10 ± 0.86 for clomiphene citrate (P-value = <0.05). The size of follicular development by day 14 was 17.6 ± 2.92 mm in Letrozole group while in Clomiphene citrate group it was 15.8 ± 3.84 mm (P-value = <0.05). The mean endometrial thickness by day 14 was 7.2 ± 0.77 mm for Letrozole and 6.8 ± 0.92 mm for clomiphene citrate (P-value = <0.05). Limitations, reasons for caution In our study, we have not considered lifestyle intervention before enrolment; although such interventions are recommended by experts, but there is currently no evidence from high quality clinical trials that they improve pregnancy outcomes in obese women. Wider implications of the findings Although Letrozole has still not gained universal acceptance as an ovulating agent for a variety of reasons, emerging evidences suggests that Letrozole could be an effective option and is non inferior to clomiphene citrate as an ovulating agent especially, in patients with non- responders to Clomiphene citrate and PCOS women. Trial registration number Not applicable

Birth Outcomes in Women With Body Mass Index of 40 kg/m2 or Greater Stratified by Planned and Actual Mode of Birth: A Systematic Review and Meta-Analysis

(Acta Obstet Gynecol Scand. 2021;100:200–209) Obese pregnant women are at increased risk of complications compared to those with normal body mass index (BMI). One systematic review found that pregnant women with BMI ≥40 kg/m2 were more likely to experience prepregnancy diabetes, gestational diabetes or hypertensive disorders during pregnancy compared with those with BMI ≤30 to 39.9 kg/m2. Among other factors, these conditions have been linked to higher rates of cesarean delivery (CD) and wound complications. Obesity in pregnancy has also been associated with increased risk of neonatal complications including Apgar scores <7 after 5 minutes and birth trauma. Vaginal delivery (VD) has generally been accepted as the preferred mode of delivery for this population. The aim of this study was to evaluate outcomes in obese pregnant women based on mode of delivery.

Effect of a Low-Glycemic Load Diet Intervention on Maternal and Pregnancy Outcomes in Obese Pregnant Women.

The increased prevalence of obese, pregnant women who have a higher risk of glucose intolerance warrants the need for nutritional interventions to improve maternal glucose homeostasis. In this study, the effect of a low-glycemic load (GL) (n = 28) was compared to a high-GL (n = 34) dietary intervention during the second half of pregnancy in obese women (body mass index (BMI) > 30 or a body fat >35%). Anthropometric and metabolic parameters were assessed at baseline (20 week) and at 28 and 34 weeks gestation. For the primary outcome 3h-glucose-iAUC (3h-incremental area under the curve), mean between-group differences were non-significant at every study timepoint (p = 0.6, 0.3, and 0.8 at 20, 28, and 34 weeks, respectively) and also assessing the mean change over the study period (p = 0.6). Furthermore, there was no statistically significant difference between the two intervention groups for any of the other examined outcomes (p ≥ 0.07). In the pooled cohort, there was no significant effect of dietary GL on any metabolic or anthropometric outcome (p ≥ 0.2). A post hoc analysis comparing the study women to a cohort of overweight or obese pregnant women who received only routine care showed that the non-study women were more likely to gain excess weight (p = 0.046) and to deliver large-for-gestational-age (LGA) (p = 0.01) or macrosomic (p = 0.006) infants. Thus, a low-GL diet consumed during the last half of pregnancy did not improve pregnancy outcomes in obese women, but in comparison to non-study women, dietary counseling reduced the risk of adverse outcomes.

The Impact of COVID-19 Lockdown on Weight Loss Program in Infertile Polycystic Ovary Syndrome Women with Obesity

Introduction: Lockdown due to the COVID-19 pandemic has caused gym closures and adjustments to ongoing weight loss programs were needed in order to keep the programs running. Little is known whether adjustments affected the success of weight reduction. Weight reduction of at least 5% is related to improved fertility and better pregnancy outcomes in obese women. This study compared success of the weight loss program in infertile polycystic ovary syndrome women with obesity who attended the program before and during lockdown due to COVID-19 pandemic. Furthermore, we checked whether there were any differences in spontaneous pregnancy rates between both groups at the end of the program. Methods: Altogether, 27 women were prospectively included to the weight loss program. Twelve women attended the 8 – week program before COVID-19 pandemic. Fifteen women began the program before the lockdown and ended it during lockdown. Due to lockdown, the program was prolonged for 4 weeks and taken online. Results: On average, prior to lockdown women achieved a BMI reduction of 6.8% whereas women that attended the program during the lockdown reduced their BMI for 3.7%. This difference was not statistically significant. No significant differences were seen in other measured anthropometric and endocrine parameters between both groups. Furthermore, there were no differences in spontaneous pregnancy rates between both groups. In women who reduced their BMI for 5% or more, spontaneous pregnancy rate was 29.4%. Discussion/Conclusions: Although statistical significance has not been reached in the present study, we have shown that lockdown due to COVID-19 pandemic has led to almost half lower BMI reduction despite adaptations and longer duration of the weight loss program. On average, BMI in the group of women that attended the program during lockdown was 3.7% lower after the end of the weight loss program. This means they did not reach the wanted 5% reduction which is known to improve fertility. We have also shown that weight reduction is the correct approach for treating infertile women with obesity, as almost 30% of those who reduced their body weight by 5% or more conceived spontaneously.

Performance of early pregnancy HbA1c for predicting gestational diabetes mellitus and adverse pregnancy outcomes in obese European women

AimsTo investigate the performance of early pregnancy HbA1c for predicting gestational diabetes mellitus (GDM) and adverse pregnancy outcomes in obese women. MethodsPost hoc analysis using data from the Vitamin D And Lifestyle Intervention for GDM prevention trials conducted across 9 European countries (2012–2014). Pregnant women (BMI ≥ 29 kg/m2) underwent a baseline HbA1c and oral glucose tolerance tests at < 20 weeks, 24–28 weeks, and 35–37 weeks. Women with GDM were referred for treatment. ResultsAmong the 869 women tested, the prevalence of GDM was 25.9% before 20 weeks, with a further 8.6% at 24–28 weeks. The areas under the curves for HbA1c at the two time points were 0.55 (0.50–0.59) and 0.54 (0.47–0.61), respectively. An early HbA1c ≥ 5.7% (39 mmol/mol) (N = 111) showed low sensitivity (18.2%) with 89.1% specificity for GDM before 20 weeks, at 24–28 weeks (sensitivity of 8.0% and specificity of 88.6% after excluding early GDM), and throughout gestation (sensitivity of 15.9% and specificity of 89.4%). The ≥ 5.7% (39 mmol/mol) threshold was significantly associated with concurrent GDM before 20 weeks (adjusted OR (aOR) 2.77(1.39–5.51)) and throughout gestation (aOR 1.72 (1.02–2.89)), but not adverse pregnancy outcomes. ConclusionsEarly pregnancy HbA1c is of limited use for predicting either GDM or adverse outcomes in overweight/obese European women.

Neonatal outcomes in obese pregnant women who develop preeclampsia.

Obesity and preeclampsia in pregnant women are each independently associated with poorer neonatal outcomes. We study obesity and preeclampsia alone and also in combination in pregnant women to determine their association with neonatal outcomes. This retrospective study (n = 664) compared four groups: 1) no preeclampsia/no obesity, 2) no preeclampsia/yes obesity, 3) yes preeclampsia/no obesity, and 4) yes preeclampsia/yes obesity. The primary outcome was neonatal intensive care unit (NICU) admission. Secondary outcomes were low birth weight, low Apgar 1 score, and low Apgar 5 score. Those with yes preeclampsia/yes obesity (OR:3.06, 95% CI:1.76, 5.32, p < 0.001) and those with yes preeclampsia/no obesity (OR:1.98, 95% CI:1.03, 3.80, p < 0.05) each had significantly higher odds for NICU admission. Those with no preeclampsia/yes obesity were not associated with NICU admission. Yes preeclampsia/yes obesity did not have any significant association with low birth weight, low Apgar 1 score, and low Apgar 5 score. Patients with preeclampsia alone or preeclampsia/obesity combined are associated with higher odds for NICU admission. However, obesity alone without preeclampsia is not associated with NICU admission. This knowledge can allow the Pediatric service prior to delivery to prepare and mitigate potential poor neonatal complications.

Metformin reduces maternal weight gain in obese pregnant women: A systematic review and meta-analysis of two randomized controlled trials.

SummaryObese pregnant women are likely to face several gestational and neonatal complications. Metformin is an effective oral antihyperglycaemic agent that is considered to be effective during pregnancy. The aim of our study was to evaluate the effect of metformin on obstetric and perinatal outcomes in obese pregnant women. Electronic databases were searched (MEDLINE, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, OVID, and Cochrane Library). The selection criteria included only randomized clinical trials (RCTs) of obese pregnant women randomized to a daily metformin regimen or to a placebo condition. The type of participants included women with a body mass index (BMI) ≥ 30 kg/m2 who did not have diabetes mellitus, any other disease, or a contraindication to metformin use. The summary measures were reported as relative risk (RR) with 95% confidence intervals (CIs). The primary outcome was the effect on maternal weight gain (MWG). Two double‐blind RCTs, including 849 obese pregnant women, were included in the meta‐analysis: 428 (50.4%) were randomized to the metformin group, and 421 (49.6%) were randomized to the placebo group. The use of metformin was significantly associated with lower MWG. Metformin was also associated with a significantly lower incidence of preeclampsia (PE) and admission to the neonatal intensive care unit (NICU). Metformin could be considered a useful drug for the treatment of obese, nondiabetic pregnant women because it can significantly decrease weight gain in pregnant women and improve perinatal outcomes by reducing the incidence of PE and NICU admission. However, women should be aware of the uncertainties concerning the long‐term effects of metformin transplacental passage on metabolic outcomes.

6: Early gestational diabetes screening in obese women: a randomized controlled trial

Although ACOG recommends screening obese women early for gestational diabetes (GDM), no studies demonstrate an improvement in perinatal outcomes. We sought to determine whether early GDM screening improves pregnancy outcomes in obese women. RCT of obese women (BMI≥30 kg/m2) with non-anomalous, singleton gestations <20wks comparing early GDM screening (14-20 wks) to routine (24-28 wks). GDM screening was performed using a 50-g, 1-hr glucose challenge test followed by a 100-g, 3-hr glucose tolerance test if ≥135 mg/dL. GDM was diagnosed using Carpenter Coustan criteria. HbA1c was measured on all patients; the provider was notified and GDM diagnosed if ≥6.5. Women not diagnosed at 14-20 wks were rescreened at 24-28 wks. Exclusion criteria were diabetes, major medical illness (cardiac, hemoglobinopathy, prednisone), bariatric surgery, and prior cesarean. The primary outcome was a composite of macrosomia (>4000g), primary cesarean, hypertensive disease of pregnancy (PIH), shoulder dystocia, neonatal hyperbilirubinemia, and neonatal hypoglycemia. We estimated a 50% incidence of the primary composite outcome; to detect a 50% reduction in the GDM patients (α=0.05, β=0.2), 58 GDM patients per group were necessary. The total sample size of 950 estimated a 14% incidence of GDM in obese women. This sample would also have 80% power to detect a 10% absolute change in the primary outcome for the entire population. Of 954 women enrolled, 912 (95.6%) had outcomes. Randomization groups were balanced at baseline for race, BMI, nulliparity, gestational age at randomization, and HbA1c. Of the 454 (49.7%) randomized to early screening, 69 (15.2%) were diagnosed with GDM: 29 (6.4%) <20 wks and 40 (8.8%) >24 wks. Of 458 randomized to routine screening, 56 (12.2%) had GDM. Early screening did not reduce the incidence of the primary outcome as it was nominally higher in the early group (59.0% vs 53.3%, p=0.08, Table 1). PIH was not reduced in the early group (13.5% vs 9.6%, p=0.06). Use of insulin was significantly increased in the early group (2.6% vs 0.7%, p=0.02). These findings were consistent when only those with GDM were compared (Table 2); considering only GDM, women in the early group were delivered earlier than the routine. In this RCT, early GDM screening in obese women was not beneficial and may have been harmful. Recommendations for early GDM screening need to be reassessed in light of these findings.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Docosahexaenoic Acid Supplementation in Pregnancy Modulates Placental Cellular Signaling and Nutrient Transport Capacity in Obese Women.

Maternal obesity in pregnancy has profound impacts on maternal metabolism and promotes placental nutrient transport, which may contribute to fetal overgrowth in these pregnancies. The fatty acid docosahexaenoic acid (DHA) has bioactive properties that may improve outcomes in obese pregnant women by modulating placental function. To determine the effects of DHA supplementation in obese pregnant women on maternal metabolism and placental function. Pregnant women were supplemented with DHA or placebo. Maternal fasting blood was collected at 26 and 36 weeks' gestation, and placentas were collected at term. Academic health care institution. Thirty-eight pregnant women with pregravid body mass index ≥30 kg/m2. DHA (800 mg, algal oil) or placebo (corn/soy oil) daily from 26 weeks to term. DHA content of maternal erythrocyte and placental membranes, maternal fasting blood glucose, cytokines, metabolic hormones, and circulating lipids were determined. Insulin, mTOR, and inflammatory signaling were assessed in placental homogenates, and nutrient transport capacity was determined in isolated syncytiotrophoblast plasma membranes. DHA supplementation increased erythrocyte (P < 0.0001) and placental membrane DHA levels (P < 0.0001) but did not influence maternal inflammatory status, insulin sensitivity, or lipids. DHA supplementation decreased placental inflammation, amino acid transporter expression, and activity (P < 0.01) and increased placental protein expression of fatty acid transporting protein 4 (P < 0.05). Maternal DHA supplementation in pregnancy decreases placental inflammation and differentially modulates placental nutrient transport capacity and may mitigate adverse effects of maternal obesity on placental function.

Improving pregnancy outcome in obese women: the UK Pregnancies Better Eating and Activity randomised controlled Trial

BackgroundObesity in pregnancy is associated with insulin resistance, which underpins many common complications including gestational diabetes mellitus (GDM) and fetal macrosomia.ObjectivesTo assess the effect of a complex behavioural intervention based on diet and physical activity (PA) on the risk of GDM and delivery of a large-for-gestational age (LGA) infant.DesignThree phases: (1) the development phase, (2) the pilot study and (3) a multicentre randomised controlled trial (RCT) comparing a behavioural intervention to improve glycaemic control with standard antenatal care in obese pregnant women. A cost–utility analysis was undertaken to estimate the cost-effectiveness of the health training (intervention) over and above standard care (control).SettingPilot study: antenatal clinics in four inner-city UK hospitals. RCT: eight antenatal clinics in eight UK inner-city hospitals.ParticipantsWomen were eligible for inclusion if they had a body mass index of ≥ 30 kg/m2, were pregnant with a single fetus and at 15+0to 18+6weeks’ gestation, were able to give written informed consent and were without predefined disorders.InterventionThe intervention comprised an initial session with a health trainer, followed by eight weekly sessions. Dietary advice recommended foods with a low dietary glycaemic index, avoidance of sugar-sweetened beverages and reduced saturated fats. Women were encouraged to increase daily PA.Main outcome measuresDevelopment phase: intervention development, acceptability and optimal approach for delivery. Pilot study: change in dietary and PA behaviours at 28 weeks’ gestation. RCT: the primary outcome of the RCT was, for the mother, GDM [as measured by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)’s diagnostic criteria] and, for the infant, LGA delivery (i.e. customised birthweight ≥ 90th centile for gestational age).ResultsDevelopment phase: following a literature meta-analysis, a study of dietary intention questionnaires and semistructured interviews, an intervention based on behavioural science was developed that incorporated optimal and acceptable methods for delivery. Pilot study: the pilot study demonstrated improvement in dietary behaviours in the intervention compared with the standard care arm but no increase in objectively measured PA. Process evaluation demonstrated feasibility and general acceptability. RCT: the RCT showed no effect of the intervention on GDM in obese pregnant women or the number of deliveries of LGA infants. There was a reduction in dietary glycaemic load (GL) and reduced saturated fat intake, an increase in PA and a modest reduction in gestational weight gain, all secondary outcomes. Lower than expected was the number of LGA infant deliveries in all women, which suggested that universal screening for GDM with IADPSG’s diagnostic criteria, and subsequent treatment, may reduce the number of deliveries of LGA infants. According to the cost–utility analysis, the estimated probability that the UK Pregnancies Better Eating and Activity Trial (UPBEAT) behavioural intervention is cost-effective at the £30,000/quality-adjusted life-year willingness-to-pay threshold was 1%.LimitationsIncluded the high refusal rate for participation and self-reported assessment of diet and PA.ConclusionsThe UPBEAT intervention, an intense theoretically based intervention in obese pregnant women, did not reduce the risk of GDM in women or the number of LGA infant deliveries, despite successfully reducing the dietary GL. Based on total cost to the NHS provider and health gains, the UPBEAT intervention provided no supporting evidence to suggest that the intervention represents value for money based on the National Institute for Health and Care Excellence benchmarks for cost-effectiveness.Future workAlternative strategies for reducing the risk of GDM in obese pregnant women and the number of LGA infant deliveries should be considered, including development of clinically effective interventions to prevent obesity in women of reproductive age, of clinically effective interventions to reduce weight retention following pregnancy and of risk stratification tools in early pregnancy.Trial registrationCurrent Controlled Trials ISRCTN89971375 and UK Clinical Research Network Portfolio 5035.FundingThis project was funded by the NIHR Programme Grant for Applied Research programme and will be published in full inProgramme Grants for Applied Research, Vol. 5, No. 10. See the NIHR journals library website for further project information. Contributions to funding were also provided by the Chief Scientist Office CZB/4/680, Scottish Government Health Directorates, Edinburgh; Guys and St Thomas’ Charity, Tommy’s Charity (Lucilla Poston, Annette L Briley, Paul T Seed) and the NIHR Biomedical Research Centre at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, UK and the Academy of Finland, Finland. Keith M Godfrey was supported by the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre. Lucilla Poston and Keith M Godfrey were supported by the European Union’s Seventh Framework Programme (FP7/2007-2013), project EarlyNutrition under grant agreement number 289346.

OP12.05: Adipocytokines as predictors for pre‐eclampsia and other adverse outcomes in obese pregnant women

OP12.05: Adipocytokines as predictors for pre‐eclampsia and other adverse outcomes in obese pregnant women

Diet-induced obesity impairs endometrial stromal cell decidualization: a potential role for impaired autophagy.

What effect does diet-induced obesity have on endometrial stromal cell (ESC) decidualization? Diet-induced obesity impairs ESC decidualization. Decidualization is important for successful implantation and subsequent health of the pregnancy. Compared with normal-weight women, obese women have lower pregnancy rates (both spontaneous and by assisted reproductive technology), higher rates of early pregnancy loss and poorer oocyte quality. Beginning at 6 weeks of age, female C57Bl/6J mice were fed either a high-fat/high-sugar diet (HF/HS; 58% Fat Energy/Sucrose) or a diet of standard mouse chow (CON; 13% Fat) for 12 weeks. At this point, metabolic parameters were measured. Some of the mice (n = 9 HF/HS and 9 CON) were mated with reproductively competent males, and implantation sites were assessed. Other mice (n = 11 HF/HS and 10 CON) were mated with vasectomized males, and artificial decidualization was induced. For in vitro human studies of primary ESCs, endometrial tissue was obtained via biopsy from normo-ovulatory patients without history of infertility (obese = BMI > 30 kg/m(2), n = 11 and lean = BMI < 25 kg/m(2), n = 7) and from patients consented for hysterectomies for a benign indication (n = 4). In vitro studies were also performed with immortalized human ESCs. ESCs were decidualized in culture for nine 9 days in the presence or absence of palmitic acid (PA), and the degree of decidualization was assessed by measuring expression of decidualization markers. The sizes of implantation sites and fetuses were analyzed in mice mated with reproductively competent males. In mice mated with vasectomized males, decidualization was induced, and uterine tissues were analyzed via hematoxylin and eosin staining, quantitative RT-PCR (RT-qPCR), and western blots. Human ESCs were cultured in vitro and induced to decidualize by treatment with cAMP and medroxyprogesterone. The level of expression of decidualization markers was assessed by RT-qPCR (mRNA) and western blotting (protein). ATP content of ESCs was measured, and levels of autophagy were assessed by western blotting of the autophagy regulators acetyl coa carboxylase (ACC) and ULK1 (Ser 317). Autophagic flux was measured by western blot of the marker LC3b-II. Mice exposed to an HF/HS diet became obese and metabolically impaired. HF/HS-exposed mice mated to reproductively competent males had smaller implantation sites in early pregnancy (P <0.001) and larger fetuses at term (P <0.05) than CON-exposed mice. In the artificial decidualization experiments, mice exposed to the HF/HS diet developed 50% smaller deciduomas than mice exposed to CON diet (P< 0.001). Human ESCs cultured in the presence of PA had markedly decreased mRNA expression of the decidualization markers, decidual prolactin (PRL) (P< 0.0001) and insulin-like growth factor binding protein 1 (IGFBP1) (P< 0.0001). Expression of PRL and IGFBP1 by mRNA were also significantly lower in early follicular phase ESCs of obese women than in those of normal-weight women (P< 0.05). Protein expression of phosphorylated ACC and phosphorylated ULK1, both activated forms, were lower in deciduomas of HF/HS mice than in those of control mice (P < 0.01). In immortalized human ESCs, LC3b-II levels were higher in decidualized cells than in controls, indicating increased autophagy. PA treatment abrogated this increase. Many aspects of obesity and metabolic impairment could contribute to the decidualization defects observed in the HF/HS-exposed mice. Although our findings suggest that both autophagy and decidualization are impaired by exposure to PA, the underlying mechanisms should be elucidated. Finally, our human patient sample size was small. Although many factors contribute to poor reproductive outcome and early pregnancy loss in obese women, our study suggests the importance of decidualization defects. Such defects may contribute to compromised endometrial receptivity and poor implantation. If defects in autophagy contribute to impaired decidualization, therapeutics could be developed to improve this process and thus improve implantation and pregnancy outcomes in obese women. Grants include NIH 5T32HD040135-12 (J.S.R.), R01 HD065435 (K.H.M.), NIH T32 HD049305 (J.L.S.) and ACOG Research Grant (M.B.S.). The authors report no conflicts of interest.

Maternal and neonatal outcomes in obese women who lose weight during pregnancy.

To evaluate neonatal and maternal outcomes in obese pregnant women whose weight gain differed from the Institute of Medicine (IOM) recommendations. Maternal and neonatal outcomes associated with weight change in pregnancy were retrospectively investigated in women with obesity (body mass index (BMI) ⩾30 kg m(-2); N=10734) who gave birth at 12 hospitals. Using a 1:1:1:1 design (n=778 matched groups), we matched women with obesity who lost, maintained, gained appropriate (IOM recommended) and gained excessive weight during pregnancy by gestational age at delivery, maternal age, race/ethnicity, prepregnancy BMI, chronic hypertension, pregestational diabetes and smoking status. Regression techniques were used to adjust for confounders and compare outcomes across weight change categories. Compared with IOM recommendations, weight loss was associated with twofold greater odds of low birth weight infants and a mean decrease in estimated blood loss of 30 ml; excessive weight gain was associated with doubled odds of gestational hypertension or preeclampsia, fourfold greater odds of macrosomia and a mean decrease in 5-min APGAR of 0.09. From lost to excessively gained weight, the odds of cesarean delivery increased 1.4 times and mean infant birth weight increased by 197 g. In contrast, the odds of small-for-gestational age were 1.8 times greater for women who lost than gained excessive weight. Weight loss in obese pregnant women is associated with increased risk for low birth weight neonates but significantly decreased or maintained risk for other maternal and neonatal morbidities, as compared with appropriate or excessive weight gain. This study supports re-evaluation of the current IOM guidelines for women with obesity.

Weight Loss Instead of Weight Gain within the Guidelines in Obese Women during Pregnancy: A Systematic Review and Meta-Analyses of Maternal and Infant Outcomes.

BackgroundControversy exists about how much, if any, weight obese pregnant women should gain. While the revised Institute of Medicine guidelines on gestational weight gain (GWG) in 2009 recommended a weight gain of 5–9 kg for obese pregnant women, many studies suggested even gestational weight loss (GWL) for obese women.ObjectivesA systematic review was conducted to summarize pregnancy outcomes in obese women with GWL compared to GWG within the 2009 Institute of Medicine guidelines (5–9 kg).DesignFive databases were searched from 1 January 2009 to 31 July 2014. The Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA Statement were followed. A modified version of the Newcastle-Ottawa scale was used to assess individual study quality. Small for gestational age (SGA), large for gestational age (LGA) and preterm birth were our primary outcomes.ResultsSix cohort studies were included, none of which assessed preterm birth. Compared to GWG within the guidelines, women with GWL had higher odds of SGA <10th percentile (adjusted odds ratio [AOR] 1.76; 95% confidence interval [CI] 1.45–2.14) and SGA <3rd percentile (AOR 1.62; 95% CI 1.19–2.20) but lower odds of LGA >90th percentile (AOR 0.57; 95% CI 0.52–0.62). There was a trend towards a graded relationship between SGA <10th percentile and each of three obesity classes (I: AOR 1.73; 95% CI 1.53–1.97; II: AOR 1.63; 95% CI 1.44–1.85 and III: AOR 1.39; 95% CI 1.17–1.66, respectively).ConclusionDespite decreased odds of LGA, increased odds of SGA and a lack of information on preterm birth indicate that GWL should not be advocated in general for obese women.

Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial

SummaryBackgroundMaternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycaemia and insulin resistance are both implicated. We aimed to establish whether the insulin sensitising drug metformin improves maternal and fetal outcomes in obese pregnant women without diabetes.MethodsWe did this randomised, double-blind, placebo-controlled trial in antenatal clinics at 15 National Health Service hospitals in the UK. Pregnant women (aged ≥16 years) between 12 and 16 weeks' gestation who had a BMI of 30 kg/m2 or more and normal glucose tolerance were randomly assigned (1:1), via a web-based computer-generated block randomisation procedure (block size of two to four), to receive oral metformin 500 mg (increasing to a maximum of 2500 mg) or matched placebo daily from between 12 and 16 weeks' gestation until delivery of the baby. Randomisation was stratified by study site and BMI band (30–39 vs ≥40 kg/m2). Participants, caregivers, and study personnel were masked to treatment assignment. The primary outcome was Z score corresponding to the gestational age, parity, and sex-standardised birthweight percentile of liveborn babies delivered at 24 weeks or more of gestation. We did analysis by modified intention to treat. This trial is registered, ISRCTN number 51279843.FindingsBetween Feb 3, 2011, and Jan 16, 2014, inclusive, we randomly assigned 449 women to either placebo (n=223) or metformin (n=226), of whom 434 (97%) were included in the final modified intention-to-treat analysis. Mean birthweight at delivery was 3463 g (SD 660) in the placebo group and 3462 g (548) in the metformin group. The estimated effect size of metformin on the primary outcome was non-significant (adjusted mean difference −0·029, 95% CI −0·217 to 0·158; p=0·7597). The difference in the number of women reporting the combined adverse outcome of miscarriage, termination of pregnancy, stillbirth, or neonatal death in the metformin group (n=7) versus the placebo group (n=2) was not significant (odds ratio 3·60, 95% CI 0·74–17·50; p=0·11).InterpretationMetformin has no significant effect on birthweight percentile in obese pregnant women. Further follow-up of babies born to mothers in the EMPOWaR study will identify longer-term outcomes of metformin in this population; in the meantime, metformin should not be used to improve pregnancy outcomes in obese women without diabetes.FundingThe Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council and National Institute for Health Research partnership.

Metformin and pregnancy outcomes in obese women

Metformin and pregnancy outcomes in obese women

Physical Activity and Maternal and Neonatal Metabolic Outcomes in Obese Pregnant Women

Maternal obesity and physical inactivity during pregnancy are independently associated with unfavorable maternal and neonatal metabolic outcomes. Previous research in non-gravid adults suggests physical activity provides protection from many chronic diseases irrespective of body weight. PURPOSE: To determine if maternal and neonatal markers of metabolic health are better in physically active obese women versus sedentary obese women during pregnancy. We hypothesize that physically active obese pregnant women will have higher insulin sensitivity, lower oxidative stress levels, lower inflammatory markers, lower blood lipids, and will deliver leaner neonates with higher insulin sensitivity compared to their sedentary obese counterparts. METHODS: Lean (LG) (n=14), obese (OBG) (n=11), and obese-physically active (OPAG) (n=11) pregnant women were compared late in their 3rd trimester. Body composition, physical fitness level (YMCA cycle test), and weekly physical activity levels (accelerometry) were assessed. Maternal plasma markers of insulin sensitivity (HOMA-IR), oxidative stress, inflammation, and lipemia were measured at baseline, during a 30-minute bout of moderate intensity exercise, and during a 1-hour recovery period. Cord blood was collected at delivery for measurement of neonatal plasma insulin sensitivity, oxidative stress, inflammation, and lipemia. Infant body composition was measured 24-48 hours postpartum. RESULTS: The OPAG spent more time in moderate physical activity (17.4%) compared to the OBG (10.3%, p<0.001) and the LG (14.1%, p=0.04). The OPAG had higher predicted fitness levels (33.6±6.2ml/kg/min) compared to the OBG (26.1±3.8ml/kg/min, p=0.001) and the LG (29.2±4.0 ml/kg/min, p=0.12). Baseline C-reactive protein levels were higher in the OBG (8.3±4.7mg/dL) compared to the LG (2.4±2.0mg/dL, p<0.001) and the OPAG (5.6±1.8mg/dL, p=0.04). Cord blood free fatty acid concentration was lower in the OPAG (0.10 ±0.05meq/L) compared to both other groups (LG: 0.18±0.08meq/L, p=0.02; OBG: 0.18 ±0.06meq/L, p=0.04). Similar trends are emerging for other outcomes. CONCLUSION: Preliminary data suggests physical activity during pregnancy in obese women may improve maternal and neonatal metabolic health.

Baseline Maternal Body Mass Index Compared With Body Mass Index at Delivery as a Predictor of Neonatal Outcomes in Obese Pregnant Women [95

Baseline Maternal Body Mass Index Compared With Body Mass Index at Delivery as a Predictor of Neonatal Outcomes in Obese Pregnant Women [95

Metformin does not improve pregnancy outcomes in obese women

Metformin does not improve pregnancy outcomes in obese women