Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring

Maternal obesity is known to increase the risk of obesity and diabetes in offspring. Though diabetes is a key risk factor for the development of chronic kidney disease (CKD), the relationship between maternal obesity and CKD has not been clearly defined. In this study, a mouse model of maternal obesity was employed to determine the impact of maternal obesity on development of diabetic nephropathy in offspring. Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow diet. At postnatal Week 8, offspring were randomly administered low dose streptozotocin (STZ, 55 mg/kg/day for five days) to induce diabetes. Assessment of renal damage took place at postnatal Week 32. We found that offspring of obese mothers had increased renal fibrosis, inflammation and oxidative stress. Importantly, offspring exposed to maternal obesity had increased susceptibility to renal damage when an additional insult, such as STZ-induced diabetes, was imposed. Specifically, renal inflammation and oxidative stress induced by diabetes was augmented by maternal obesity. Our findings suggest that developmental programming induced by maternal obesity has implications for renal health in offspring. Maternal obesity should be considered a risk factor for CKD

Maternal obesity during pregnancy and lactation influences offspring obesogenic adipogenesis but not developmental adipogenesis in mice

Obesity is an escalating health crisis of pandemic proportions and by all accounts it has yet to reach its peak. Growing evidence suggests that obesity may have its origins in utero. Recent studies have shown that maternal obesity during pregnancy may promote adipogenesis in offspring. However, these studies were largely based on cell culture models. Whether or not maternal obesity impacts on offspring adipogenesis in vivo remains to be fully established. Furthermore, in vivo adipogenic differentiation has been shown to happen at distinct time periods, one during development (developmental adipogenesis—which is complete by 4 weeks of age in mice) and another in adulthood in response to feeding a high-fat (HF) diet (obesogenic adipogenesis). We therefore set out to determine whether maternal obesity impacted on offspring adipocyte hyperplasia in vivo and whether maternal obesity impacted on developmental or obesogenic adipogenesis, or both. Our findings reveal that maternal obesity is associated with enhanced obesogenic adipogenesis in HF-fed offspring. Interestingly, in newly weaned (4-week-old) offspring, maternal obesity is associated with adipocyte hypertrophy, but there were no changes in adipocyte number. Our results suggest that maternal obesity impacts on offspring obesogenic adipogenesis but does not affect developmental adipogenesis

Do Gestational Obesity and Gestational Diabetes Have an Independent Effect on Neonatal Adiposity? Results of Mediation Analysis from a Cohort Study in South India.

PURPOSE: Neonates born to mothers with obesity or gestational diabetes mellitus (GDM) have an increased chance of various metabolic disorders later in life. In India, it is unclear whether maternal obesity or GDM is related to offspring adiposity. We aimed to understand the independent effect of maternal obesity and GDM with neonatal adiposity and whether GDM has a mediating effect between maternal obesity and neonatal adiposity. METHODS: We recruited a cohort of 1120 women (between April 2016 and February 2019) from the public hospitals in Bangalore, India, who voluntarily agreed to participate and provided written informed consent. The primary outcome was neonatal adiposity, defined as the sum of skinfold thickness >85th percentile. Exposure included maternal obesity, defined as >90th percentile of skinfold thickness. GDM, the potential mediator, was classified using the World Health Organization criteria by oral glucose tolerance test. Binary logistic regression was applied to test the effect of maternal obesity and GDM on neonatal adiposity, adjusting for potential confounders. We used Paramed command in STATA version 14 for analyzing mediating effects. RESULTS: We found that maternal obesity (odds ratio (OR)=2.16, 95% CI 1.46, 3.18) and GDM (OR=2.21, 95% CI1.38, 3.52) have an independent effect on neonatal adiposity. GDM significantly mediates 25.2% of the total effect between maternal obesity and neonatal adiposity, (natural direct effect OR = 1.16 95% CI 1.04, 1.30) with significant direct effect of maternal obesity (natural direct effect OR = 1.90 95% CI 1.16, 3.10) and significant total effect (OR=2.20 95% CI 1.35, 3.58). CONCLUSION: We showed that maternal obesity and GDM are independently associated with offspring adiposity. Also, GDM mediates the association of maternal obesity on adiposity in children. Interventions focused on obesity prevention in women, and effective screening and management of GDM may contribute to reducing childhood obesity in India

Maternal obesity in Africa : a systematic review and meta-analysis

Background: Maternal obesity is emerging as a public health problem, recently highlighted together with maternal under-nutrition as a ‘double burden’, especially in African countries undergoing social and economic transition. This systematic review was conducted to investigate the current evidence on maternal obesity in Africa. Methods: MEDLINE, EMBASE, Scopus, CINAHL and PsycINFO were searched (up to August 2014) and identified 29 studies. Prevalence, associations with socio-demographic factors, labour, child and maternal consequences of maternal obesity were assessed. Pooled risk ratios comparing obese and non-obese groups were calculated. Results: Prevalence of maternal obesity across Africa ranged from 6.5 to 50.7%, with older and multiparous mothers more likely to be obese. Obese mothers had increased risks of adverse labour, child and maternal outcomes. However, non-obese mothers were more likely to have low-birthweight babies. The differences in measurement and timing of assessment of maternal obesity were found across studies. No studies were identified either on the knowledge or attitudes of pregnant women towards maternal obesity; or on interventions for obese pregnant women. Conclusions: These results show that Africa's levels of maternal obesity are already having significant adverse effects. Culturally adaptable/sensitive interventions should be developed while monitoring to avoid undesired side effects

From Fatalism to Mitigation: a Conceptual Framework for Mitigating Fetal Programming of Chronic Disease by Maternal Obesity

Prenatal development is recognized as a critical period in the etiology of obesity and cardiometabolic disease. Potential strategies to reduce maternal obesity-induced risk later in life have been largely overlooked. In this paper, we first propose a conceptual framework for the role of public health and preventive medicine in mitigating the effects of fetal programming. Second, we review a small but growing body of research (through August 2015) that examines interactive effects of maternal obesity and two public health foci – diet and physical activity – in the offspring. Results of the review support the hypothesis that diet and physical activity after early life can attenuate disease susceptibility induced by maternal obesity, but human evidence is scant. Based on the review, we identify major gaps relevant for prevention research, such as characterizing the type and dose response of dietary and physical activity exposures that modify the adverse effects of maternal obesity in the offspring. Third, we discuss potential implications of interactions between maternal obesity and postnatal dietary and physical activity exposures for interventions to mitigate maternal obesity-induced risk among children. Our conceptual framework, evidence review, and future research directions offer a platform to develop, test, and implement fetal programming mitigation strategies for the current and future generations of children

Association of Maternal Obesity and Pregnancy Outcomes

Background: The prevalence of obesity is increasing globally, causing various possible disorders and complications. Maternal and perinatal morbidity and mortality might potentially be affected by maternal obesity. This study aimed to evaluate the association between maternal obesity and pregnancy outcomes.Methods: This retrospective cohort study was part of a larger cohort study performed from July 2016 to July 2017 in West Java, including 223 pregnant women with normal fetuses, who were obese or non-obese pre-pregnancy. Underweight women were excluded. Data on pregnancy outcomes consisting of Caesarean section, preeclampsia, premature rupture of membrane (PROM), preterm birth, post-term birth, small for gestational age (SGA), and large for gestational age (LGA) were collected. The association with maternal obesity was analyzed using the Fisher’s Exact Test to determine the association with a 95% confidence interval, and a p-value <0.05 was considered significant.Results: There was an association between maternal obesity and Caesarean section, with an increased risk in obese mothers compared to non-obese mothers (RR 2.398 CI 1.328-4.329). There was no significant association between maternal obesity and preeclampsia, PROM, preterm birth, post-term birth, SGA, and LGA.Conclusion: Maternal obesity is associated with Caesarean section. A more comprehensive approach is essential for obese pregnant women to ensure the health of both the mother and the infant

The Influence Of Maternal Obesity On Adolescent Obesity In Santiago, Chile

Objective: To examine the relationship between adolescent obesity and associated maternal obesity variables of interest, specifically maternal pre-pregnancy obesity and maternal obesity 10 years postpartum. Design: Secondary data analysis of a longitudinal study in Santiago, Chile (N=786 adolescents). Variables were extracted from multiple waves of data collection. The maternal obesity variables of interest and covariates were stratified by gender and associations of interest examined using univariate logistic regression analyses and multivariate logistic regression models with missing data imputation. Covariates included were birth weight percentile, breastfeeding for 6 months, father\u27s presence, maternal age, and maternal education. Results: Adolescent obesity was associated with maternal obesity in both males and females. Female obese adolescents had a positive association with maternal obesity at 10 years postpartum (OR= 3.65, CI= 1.19, 11.14) and a negative association with father\u27s presence in the household (OR= 0.236, CI= 0.07, 0.76). Among male adolescents obesity was positively associated with maternal pre-pregnancy obesity (OR= 9.59, CI= 1.25, 73.31). Conclusions: Maternal obesity status is an important predictor of adolescent obesity. Maternal obesity was a significant predictor of obesity among males and females but at chronologically different periods of the child\u27s development. This may be attributed to gender related differences in genetic, behavioral, and/or environmental factors. Adolescent obesity intervention programs should provide varied approaches that cater to the different needs of males and females. Future research on maternal and other influences of adolescent obesity should focus on quantitative collection of parental and peer-related measures of anthropometrics, physical activity, dietary habits, as well as other sociobehavioral determinants of health

Maternal obesity predisposes offspring towards the development of chronic kidney disease

Obesity together with insulin resistance promotes multiple metabolic abnormalities and is strongly associated with increased risk of chronic disease including type 2 diabetes (T2D), cardiovascular disease (CVD) and chronic kidney disease (CKD). The incidence of obesity is rising and affects all different stages of the lifespan. Importantly, obesity in women of reproductive has potential ramifications for offspring health. Maternal obesity is known to influence offspring development of obesity, T2D and CVD. In contrast, the relationship between maternal obesity and CKD has been less clearly defined. This thesis aims to determine whether maternal obesity increases offspring risk of CKD. Rodent models of maternal obesity were employed by feeding dams a high fat diet (HFD) for 6 weeks prior to mating, during gestation and lactation. At Day 20, there was evidence of renal inflammation and oxidative stress in the kidneys of rat offspring and the nuclear hormone receptor Farnesoid X receptor (FXR) was pathogenically implicated. At postnatal Week 9, the kidneys of rat offspring of obese mothers demonstrated increased markers of inflammation, oxidative stress and fibrosis, exacerbated by HFD-feeding in the offspring. The glucose-like peptide-1 (GLP-1) analogue, Exendin-4, ameliorated the negative renal effects of maternal. GLP-1 analogues may be useful for protecting against the deleterious effects of maternal obesity on renal physiology in offspring. Consistent with the metabolic effects observed in the rat, mouse offspring of obese mothers at postnatal Week 32 had increased fat deposition, insulin resistance and impaired glucose tolerance and renal pathology. Furthermore, postnatal feeding of HFD in offspring augmented these effects. Offspring of obese mothers were more prone to renal damage when an additional insult, such as streptozotocin-induced diabetes, was imposed. However, offspring obesity induced by HFD was the strongest predictor of weight gain, glucose intolerance, albuminuria and renal damage, which appeared to overpower the effect of maternal obesity. This thesis suggests that developmental programming resulting from in utero exposure to maternal obesity predisposes offspring towards CKD. Foetal exposure to maternal obesity should be considered as a significant risk factor for CKD

Maternal Obesity and Fetal Macrosomia: An Integrative Review of the Literature Regarding Interventions

Research suggests pre-pregnancy obesity is associated with an increased risk of macrosomia in the newborn. Since women are expected to gain weight during pregnancy, the standard recommendation of weight loss for obesity is not ideal for this population. In this systematic review of the literature regarding interventions for maternal obesity to reduce fetal macrosomia, 149 articles were screened using three different databases to identify recent randomized controlled trials related to this topic. A total of 11 full text articles were analyzed and included in the review. The articles addressed nutritional, lifestyle, and pharmacological interventions. The results indicated there is currently insufficient evidence to support specific treatment options for women with obesity during pregnancy to reduce the risk of fetal macrosomia