RESUMO
In utero exposure to maternal obesity programs increased obesity risk. Animal models show that programmed offspring obesity is preceded by hyperphagia, but the mechanisms that mediate these changes are unknown. Using a mouse model of maternal obesity, we observed increased intake of a high-fat diet (HFD) in offspring of obese mothers that precedes the development of obesity. Through small RNA sequencing, we identified programmed overexpression of hypothalamic miR-505-5p that is established in the fetus, lasts to adulthood and is maintained in hypothalamic neural progenitor cells cultured in vitro. Metabolic hormones and long-chain fatty acids associated with obesity increase miR-505-5p expression in hypothalamic neurons in vitro. We demonstrate that targets of miR-505-5p are enriched in fatty acid metabolism pathways and overexpression of miR-505-5p decreased neuronal fatty acid metabolism in vitro. miR-505-5p targets are associated with increased BMI in human genetic studies. Intra-cerebroventricular injection of miR-505-5p in wild-type mice increased HFD intake, mimicking the phenotype observed in offspring exposed to maternal obesity. Conversely, maternal exercise intervention in an obese mouse pregnancy rescued the programmed increase of hypothalamic miR-505-5p in offspring of obese dams and reduced HFD intake to control offspring levels. This study identifies a novel mechanism by which maternal obesity programs obesity in offspring via increased intake of high-fat foods.
Assuntos
Dieta Hiperlipídica , Ácidos Graxos , Hipotálamo , MicroRNAs , Obesidade Materna , Animais , Feminino , Humanos , Masculino , Camundongos , Gravidez , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Hipotálamo/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , MicroRNAs/genética , Neurônios/metabolismo , Obesidade/metabolismo , Obesidade/genética , Obesidade Materna/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/genéticaRESUMO
Obesity and gestational diabetes (GDM) impact fetal growth during pregnancy. Iron is an essential micronutrient needed for energy-intense feto-placental development, but if mis-handled can lead to oxidative stress and ferroptosis (iron-dependent cell death). In a mouse model showing maternal obesity and glucose intolerance, we investigated the association of materno-fetal iron handling and placental ferroptosis, oxidative damage and stress signalling activation with fetal growth. Female mice were fed a standard chow or high fat, high sugar (HFHS) diet during pregnancy and outcomes were measured at day (d)16 or d19 of pregnancy. In HFHS-fed mice, maternal hepcidin was reduced and iron status maintained (tissue iron levels) at both d16 and d19. However, fetal weight, placental iron transfer capacity, iron deposition, TFR1 expression and ERK2-mediated signalling were reduced and oxidative damage-related lipofuscin accumulation in the placenta was increased in HFHS-fed mice. At d19, whilst TFR1 remained decreased, fetal weight was normal and placental weight, iron content and iron transporter genes (Dmt1, Zip14, and Fpn1) were reduced in HFHS-fed mice. Furthermore, there was stress kinase activation (increased phosphorylated p38MAPK, total ERK and JNK) in the placenta from HFHS-fed mice at d19. In summary, a maternal HFHS diet during pregnancy impacts fetal growth trajectory in association with changes in placental iron handling, ferroptosis and stress signalling. Downregulation of placental iron transporters in HFHS mice may protect the fetus from excessive oxidative iron. These findings suggest a role for alterations in placental iron homeostasis in determining perinatal outcomes of pregnancies associated with GDM and/or maternal obesity.
Assuntos
Ferroptose , Obesidade Materna , Humanos , Gravidez , Feminino , Animais , Camundongos , Ferro , Peso Fetal , Placenta , Feto , Dieta Hiperlipídica/efeitos adversosRESUMO
BACKGROUND: Maternal overweight and obesity have been associated with an increased risk of atopic dermatitis (AD) in the offspring, but the underlying mechanisms are unclear. Vernix caseosa (VC) is a proteolipid material covering the fetus produced during skin development. However, whether maternal prepregnancy weight excess influences fetal skin development is unknown. Characterizing the VC of newborns from mothers with prepregnancy overweight and obesity might reveal AD-prone alterations during fetal skin development. OBJECTIVE: We sought to explore AD biomarkers and staphylococcal loads in VC from the offspring of mothers who were overweight/obese (O/O) before pregnancy versus in those from offspring of normal weight mothers. METHODS: The VC of newborns of 14 O/O and 12 normal weight mothers were collected immediately after birth. Biomarkers were determined by ELISA and staphylococcal species by quantitative PCR. RESULTS: The VC from the O/O group showed decreased expression of skin barrier proteins (filaggrin and loricrin) and increased levels of proinflammatory biomarkers (IgA, thymic stromal lymphopoietin [TSLP], S100A8, IL-25, and IL-33). No differences in concentrations of antimicrobial peptides and enzymes were detected. The VC from the O/O group had a lower Staphylococcus epidermidis and Staphylococcus hominis commensal bacterial load, whereas Staphylococcus aureus bacterial load was not significantly different between the 2 groups. Maternal body mass index was negatively correlated with VC filaggrin expression and S epidermidis load and was positively associated with TSLP concentration. One-year follow-up established that the offspring of O/O mothers had a higher incidence of AD that was specifically linked with decreased VC filaggrin expression and lower S epidermidis load. CONCLUSIONS: VC from neonates of mothers with prepregnancy overweight and obesity exhibit skin barrier molecular alterations and staphylococcal dysbiosis that suggest early mechanistic clues to this population's increased risk of AD.
Assuntos
Dermatite Atópica , Obesidade Materna , Verniz Caseoso , Humanos , Recém-Nascido , Feminino , Gravidez , Dermatite Atópica/patologia , Proteínas Filagrinas , Obesidade Materna/metabolismo , Obesidade Materna/patologia , Verniz Caseoso/metabolismo , Sobrepeso , Pele/patologia , Citocinas/metabolismo , Linfopoietina do Estroma do Timo , Obesidade/patologia , Biomarcadores/metabolismoRESUMO
Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean.NEW & NOTEWORTHY Offspring from obese parents are more susceptible to kidney injury and worse outcomes following an acute ischemia-reperfusion insult. Male, but not female, offspring from obese parents exhibit increased blood pressure early in life. Female offspring are partially protected against major kidney injury induced by ischemia-reperfusion.
Assuntos
Injúria Renal Aguda , Rim , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão , Animais , Masculino , Feminino , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/patologia , Rim/fisiopatologia , Rim/patologia , Rim/metabolismo , Fatores Sexuais , Obesidade/complicações , Obesidade/fisiopatologia , Dieta Hiperlipídica , Gravidez , Lipocalina-2/metabolismo , Obesidade Materna/metabolismo , Obesidade Materna/complicações , Obesidade Materna/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal , Camundongos , Fatores de Risco , Modelos Animais de Doenças , Biomarcadores/sangueRESUMO
BACKGROUND: Children born to obese mothers are at increased risk of developing mood disorders and cognitive impairment. Experimental studies have reported structural changes in the brain such as the gliovascular unit as well as activation of neuroinflammatory cells as a part of neuroinflammation processing in aged offspring of obese mothers. However, the molecular mechanisms linking maternal obesity to poor neurodevelopmental outcomes are not well established. The ephrin system plays a major role in a variety of cellular processes including cell-cell interaction, synaptic plasticity, and long-term potentiation. Therefore, in this study we determined the impact of maternal obesity in pregnancy on cortical, hippocampal development, vasculature and ephrin-A3/EphA4-signaling, in the adult offspring in mice. METHODS: Maternal obesity was induced in mice by a high fat/high sugar Western type of diet (HF/HS). We collected brain tissue (prefrontal cortex and hippocampus) from 6-month-old offspring of obese and lean (control) dams. Hippocampal volume, cortical thickness, myelination of white matter, density of astrocytes and microglia in relation to their activity were analyzed using 3-D stereological quantification. mRNA expression of ephrin-A3, EphA4 and synaptic markers were measured by qPCR in the brain tissue. Moreover, expression of gap junction protein connexin-43, lipocalin-2, and vascular CD31/Aquaporin 4 were determined in the hippocampus by immunohistochemistry. RESULTS: Volume of hippocampus and cortical thickness were significantly smaller, and myelination impaired, while mRNA levels of hippocampal EphA4 and post-synaptic density (PSD) 95 were significantly lower in the hippocampus in the offspring of obese dams as compared to offspring of controls. Further analysis of the hippocampal gliovascular unit indicated higher coverage of capillaries by astrocytic end-feet, expression of connexin-43 and lipocalin-2 in endothelial cells in the offspring of obese dams. In addition, offspring of obese dams demonstrated activation of microglia together with higher density of cells, while astrocyte cell density was lower. CONCLUSION: Maternal obesity affects brain size, impairs myelination, disrupts the hippocampal gliovascular unit and decreases the mRNA expression of EphA4 and PSD-95 in the hippocampus of adult offspring. These results indicate that the vasculature-glia cross-talk may be an important mediator of altered synaptic plasticity, which could be a link between maternal obesity and neurodevelopmental/neuropsychiatric disorders in the offspring.
Assuntos
Obesidade Materna , Efeitos Tardios da Exposição Pré-Natal , Humanos , Criança , Camundongos , Animais , Feminino , Gravidez , Idoso , Lactente , Obesidade Materna/metabolismo , Lipocalina-2/metabolismo , Efrinas/metabolismo , Efrina-A3/genética , Efrina-A3/metabolismo , Filhos Adultos , Células Endoteliais/metabolismo , Obesidade/metabolismo , Hipocampo/metabolismo , RNA Mensageiro/metabolismo , Conexinas/genética , Conexinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/metabolismoRESUMO
Maternal obesity before or during pregnancy has been associated previously in offspring with a wide range of poor neurodevelopmental outcomes and mental health problems. The effects of maternal obesity on offspring brain structure and function that may be responsible for these poor outcomes are not well understood. We, therefore, undertook a systematic review of magnetic resonance imaging (MRI) studies that have assessed the associations of maternal obesity with brain measures in offspring. A systematic search was conducted in PubMed, Web of Science, Scopus, and PsycINFO on August 20, 2023. Of 15 eligible studies, seven employed functional MRI (fMRI), five diffusion tensor imaging (DTI), and four anatomical MRI (one used both DTI and anatomical MRI) in the offspring. The ages of offspring varied widely: one was a study of fetuses in utero, five of neonates, one of infants, five of school-aged children, two of both neonates and infants, and one of both children and adults. Collectively, 12 studies reported significant associations of maternal obesity with structural or functional alterations of the offspring's brain, most frequently in the prefrontal cortex and limbic system. In conclusion, maternal obesity appears to have a profound influence on offspring brain development, particularly within the prefrontal and limbic networks that regulate emotion and behavior. Further studies are needed to identify how changes in brain structure and function mediate the effects of maternal obesity on long-term emotional and behavioral outcomes, as well as the molecular pathways through which maternal obesity alters offspring brain development.
Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Obesidade Materna , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem , Efeitos Tardios da Exposição Pré-Natal/patologiaRESUMO
Obesity is becoming a worldwide pandemic with over one billion people affected. Of women in the United States, who are of childbearing age, two-thirds of them are considered overweight/obese. Offspring of women with obesity have a greater likelihood of developing cardiometabolic disease later in life, therefore making obesity a transgenerational issue. Emerging topics such as maternal microbial dysbiosis with altered levels of bacterial phyla and maternal obesity programming offspring cardiometabolic disease are a novel area of research discussed in this review. In the authors' opinion, beneficial therapeutics will be developed from knowledge of bacterial-host interactions at the most specific level possible. Although there is an abundance of obesity-related microbiome research, it is not concise, readily available, nor easy to interpret at this time. This review details the current knowledge regarding the relationship between obesity and the gut microbiome, with an emphasis on maternal obesity.
Assuntos
Doenças Cardiovasculares , Microbiota , Obesidade Materna , Humanos , Feminino , Gravidez , Disbiose , Obesidade/terapiaRESUMO
BACKGROUND: Rodent models suggest that in utero exposure to under and overnutrition programs offspring physical activity (PA) behaviors. Such nexus has not been established in humans. This study evaluated the association of early pregnancy maternal adiposity with offspring PA at age 2 years (2-yo-PA) taking into consideration prenatal and postnatal factors. METHODS: Women (n = 153) were enrolled early in pregnancy (<10 weeks). At enrollment, maternal adiposity [air displacement plethysmography, fat mass index (FMI, kg/m2)] and PA (accelerometers, activity counts) were measured, and age, race, and education self-reported. Gestational weight gain was measured at the research facility. Offspring birthweight and sex were self-reported. At age 2 years, parental feeding practices (child feeding questionnaire) were assessed, whereas anthropometrics (length and weight) and physical activity (accelerometers) were objectively measured. Offspring body mass index z-scores were calculated. Generalized linear regression analysis modeled the association of maternal FMI and 2-yo-PA [average activity counts (AC)4/day]. RESULTS: In bivariate associations, 2-yo-PA did not associate with maternal FMI (ß = -0.22, CI = -0.73 to 0.29, p = 0.398). However, maternal FMI interacted with offspring sex in association with 2-yo-PA. Specifically, 2-yo-PA was lower in girls (ß = -1.14, CI = -2.1 to -0.18, p = 0.02) compared to boys when maternal FMI was ≥7 kg/m2. When stratified by sex, 2-yo-PA of girls negatively associated with maternal FMI (ß = -0.82, CI = -1.43 to 0.29, p = 0.009) while no association was found between maternal FMI and boy's PA (ß = 0.32, CI = -0.38 to 1.01, p = 0.376). CONCLUSIONS: The association of 2-yo-PA and early pregnancy maternal adiposity was modified by offspring sex. Offspring's physical activity decreased with increasing early pregnancy adiposity maternal in girls but not boys in second parity dyads.
Assuntos
Adiposidade , Obesidade Materna , Masculino , Criança , Gravidez , Humanos , Feminino , Pré-Escolar , Obesidade , Índice de Massa Corporal , Exercício Físico , AntropometriaRESUMO
OBJECTIVE: To evaluate the association between maternal BMI and congenital heart defects (CHDs) in the offspring when including live births, stillbirths, aborted and terminated pregnancies and to investigate if maternal interpregnancy weight changes between the first and second pregnancy influences the risk of foetal CHDs. METHODS: A nationwide cohort study of all singleton pregnancies in Denmark from 2008 to 2018. Data were retrieved from the Danish Foetal Medicine Database, which included both pre- and postnatal diagnoses of CHDs. Children or foetuses with chromosomal aberrations were excluded. Odds ratios were calculated with logistic regression models for CHDs overall, severe CHDs and five of the most prevalent subtypes of CHDs. RESULTS: Of the 547 105 pregnancies included in the cohort, 5 442 had CHDs (1.0%). Risk of CHDs became gradually higher with higher maternal BMI; for BMI 25-29.9 kg/m2, adjusted odds ratio (aOR) 1.17 (95% CI 1.10-1.26), for BMI 30-34.9 kg/m2, aOR 1.21 (95% CI 1.09-1.33), for BMI 35-39.9 kg/m2, aOR 1.29 (95% CI 1.11-1.50) and for BMI ≥ 40 kg/m2, aOR 1.85 (95% CI 1.54-2.21). Data was adjusted for maternal age, smoking status and year of estimated due date. The same pattern was seen for the subgroup of severe CHDs. Among the atrioventricular septal defects (n = 231), an association with maternal BMI ≥ 30 kg/m2 was seen, OR 1.67 (95% CI 1.13-2.44). 109 654 women were identified with their first and second pregnancies in the cohort. Interpregnancy BMI change was associated with the risk of CHDs in the second pregnancy (BMI 2 to < 4 kg/m2: aOR 1.29, 95% CI 1.09-1.53; BMI ≥ 4 kg/m2: aOR 1.36, 95% CI 1.08-1.68). CONCLUSION: The risk of foetal CHDs became gradually higher with higher maternal BMI and interpregnancy weight increases above 2 BMI units were also associated with a higher risk of CHDs.
Assuntos
Cardiopatias Congênitas , Obesidade Materna , Humanos , Feminino , Gravidez , Obesidade Materna/epidemiologia , Obesidade Materna/complicações , Cardiopatias Congênitas/epidemiologia , Adulto , Dinamarca/epidemiologia , Estudos de Coortes , Índice de Massa Corporal , Fatores de Risco , Recém-NascidoRESUMO
BACKGROUND: Preconception or antenatal lifestyle interventions in women with obesity may prevent adverse cardiovascular outcomes in the child, including cardiac remodelling. We undertook a systematic review of the existing data to examine the impact of randomised controlled trials of lifestyle interventions in pregnant women with obesity on offspring cardiac remodelling and related parameters of cardiovascular health. METHODS: This review was registered with PROSPERO (CRD42023454762) and aligns with PRISMA guidelines. PubMed, Embase, and previous reviews were systematically searched. Follow-up studies from randomised trials of lifestyle interventions in pregnant women with obesity, which included offspring cardiac remodelling or related cardiovascular parameters as outcome measures, were included based on pre-defined inclusion criteria. RESULTS: Eight studies from five randomised controlled trials were included after screening 3252 articles. Interventions included antenatal exercise (n = 2), diet and physical activity (n = 2), and preconception diet and physical activity (n = 1). Children were <2-months to 3-7-years-old, with sample sizes ranging between n = 18-404. Reduced cardiac remodelling, with reduced interventricular septal wall thickness, was consistently reported. Some studies identified improved systolic and diastolic function and a reduced resting heart rate. Risk of bias analyses rated all studies as 'fair' (some risk of bias). A high loss-to-follow-up was a common limitation. CONCLUSION: Although there is some evidence to suggest that lifestyle interventions in women with obesity may limit offspring cardiac remodelling, further high-quality longitudinal studies with larger sample sizes are required to confirm these observations and to determine whether these changes persist to adulthood. Child offspring cardiovascular health benefits of preconception and antenatal lifestyle interventions in women with obesity.
Assuntos
Obesidade Materna , Humanos , Feminino , Gravidez , Cuidado Pré-Concepcional/métodos , Estilo de Vida , Criança , Doenças Cardiovasculares/prevenção & controle , Remodelação Ventricular/fisiologia , Cuidado Pré-Natal/métodos , Exercício Físico/fisiologia , Complicações na Gravidez/prevenção & controle , Pré-Escolar , Efeitos Tardios da Exposição Pré-Natal , Adulto , Lactente , Obesidade/complicações , Obesidade/fisiopatologiaRESUMO
Maternal obesity increases the risk of adverse pregnancy outcomes. The mechanisms that contribute to this elevated risk are unclear but may be related to greater activity of the sympathetic nervous system, which is associated with hypertensive disorders of pregnancy. We hypothesized that resting muscle sympathetic nerve activity (MSNA) would be greater in women with obesity during pregnancy when compared with normal-weight women. Blood pressure, heart rate, and MSNA were recorded during 5 min of supine rest in 14 normal-weight women [body mass index (BMI) 22.1 ± 2.1 (SD) kg/m2] and 14 women with obesity (BMI 33.9 ± 3.5 kg/m2) during (early and late) pregnancy and postpartum. All women had uncomplicated pregnancies. Resting MSNA burst frequency was not different between groups during early (normal weight 17 ± 10 vs. obesity 22 ± 15 bursts/min, P = 0.35) but was significantly greater in the obesity group during late pregnancy (23 ± 13 vs. 35 ± 15 bursts/min, P = 0.031) and not different postpartum (10 ± 6 vs. 9 ± 7 bursts/min, P = 0.74). These findings were also apparent when comparing burst incidence and total activity. Although still within the normotensive range, systolic blood pressure was greater in the obesity group across all time points (P = 0.002). Diastolic blood pressure was lower during pregnancy compared with postpartum (P < 0.001) and not different between groups (P = 0.488). Heart rate increased throughout pregnancy in both groups (P < 0.001). Our findings suggest that maternal obesity is associated with greater increases in sympathetic activity even during uncomplicated pregnancy. Future research is needed to determine if this is linked with an increased risk of adverse outcomes or is required to maintain homeostasis in pregnancy.NEW & NOTEWORTHY The impact of maternal obesity on resting muscle sympathetic nerve activity was examined during (early and late) and after uncomplicated pregnancy. Resting muscle sympathetic nerve activity is not different during early pregnancy or postpartum but is significantly elevated in women with obesity during late pregnancy when compared with normal-weight women. Future research is needed to determine if this is linked with an increased risk of adverse outcomes or is required to maintain homeostasis in pregnancy.
Assuntos
Obesidade Materna , Humanos , Feminino , Gravidez , Masculino , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Músculo Esquelético/inervação , Obesidade/diagnóstico , Sistema Nervoso SimpáticoRESUMO
Maternal obesity is associated with an increased risk of psychiatric disorders such as anxiety, depression, schizophrenia and autism spectrum disorder in the offspring. While numerous studies focus on preventive measures targeting the mothers, only a limited number provide practical approaches for addressing the damages once they are already established. We have recently demonstrated the interplay between maternal obesity and treatment with cannabidiol (CBD) on hypothalamic inflammation and metabolic disturbances, however, little is known about this relationship on behavioral manifestations and neurochemical imbalances in other brain regions. Therefore, here we tested whether CBD treatment could mitigate anxiety-like and social behavioral alterations, as well as neurochemical disruptions in both male and female offspring of obese dams. Female Wistar rats were fed a cafeteria diet for 12 weeks prior to mating, and during gestation and lactation. Offspring received CBD (50 mg/kg) from weaning for 3 weeks. Behavioral tests assessed anxiety-like manifestations and social behavior, while neuroinflammatory and neurochemical markers were evaluated in the prefrontal cortex (PFC) and hippocampus. CBD treatment attenuated maternal obesity-induced anxiety-like and social behavioral alterations, followed by rescuing effects on imbalanced neurotransmitter and endocannabinoid concentrations and altered expression of glial markers, CB1, oxytocin and dopamine receptors, with important differences between sexes. Overall, the findings of this study provide insight into the signaling pathways for the therapeutic benefits of CBD on neuroinflammation and neurochemical imbalances caused by perinatal maternal obesity in the PFC and the hippocampus, which translates into the behavioral manifestations, highlighting the sexual dimorphism encompassing both the transgenerational effect of obesity and the endocannabinoid system.
Assuntos
Ansiedade , Comportamento Animal , Canabidiol , Hipocampo , Obesidade Materna , Córtex Pré-Frontal , Efeitos Tardios da Exposição Pré-Natal , Ratos Wistar , Animais , Feminino , Canabidiol/farmacologia , Gravidez , Ratos , Masculino , Obesidade Materna/metabolismo , Ansiedade/metabolismo , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Comportamento Social , Obesidade/metabolismo , Endocanabinoides/metabolismoRESUMO
AIM: A primary goal of obstetric care of women with type 1 diabetes (T1D) is to reduce the risks of preterm birth (PTB). Besides hyperglycaemia, maternal obesity is an important risk factor for PTB in T1D. However, it's unclear if public health efforts decreased risks of maternal obesity and PTB in pregnancies with T1D. We examined time-trends over the last 20 years in the distribution of gestational ages at birth (GA) in offspring of women with T1D in Sweden, and in maternal BMI in the same mothers. METHODS: Population-based cohort study, using data from national registries in Sweden. To capture differences not only in the median values, we used quantile regression models to compare the whole distributions of GA's and early pregnancy BMI between deliveries in 1998-2007 (P1) and 2008-2016 (P2). Multivariable models were adjusted for differences in maternal age, smoking and education between periods 1 and 2. RESULTS: The study included 7639 offspring of women with T1D between 1998 and 2016. The 10% percentile GA, increased with 0.09 days (95% CI: -0.11 to 0.35) between P1 and P2. The 90% percentile for BMI was 1.20 kg/m2 higher (95% CI: 0.57 to 1.83) in P2. Risks of PTB remained stable over time also when adjusting for maternal BMI. CONCLUSION: Despite modern diabetes management, the distribution of GA, and consequently the risk of PTB in T1D, remained unchanged from 1998 to 2016. During the same time, maternal BMI increased, particularly in the already obese.
Assuntos
Diabetes Mellitus Tipo 1 , Obesidade Materna , Gravidez em Diabéticas , Nascimento Prematuro , Humanos , Feminino , Gravidez , Suécia/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Nascimento Prematuro/epidemiologia , Adulto , Gravidez em Diabéticas/epidemiologia , Obesidade Materna/epidemiologia , Obesidade Materna/complicações , Recém-Nascido , Índice de Massa Corporal , Sistema de Registros , Estudos de Coortes , Fatores de Risco , Idade Gestacional , Adulto JovemRESUMO
BACKGROUND: Maternal obesity is associated with stillbirth, but uncertainty persists around the effects of higher obesity classes. We sought to compare the risk of stillbirth associated with maternal obesity alone versus maternal obesity and additional or undiagnosed factors contributing to high-risk pregnancy. METHODS: We conducted a retrospective cohort study using the Better Outcomes Registry and Network (BORN) for singleton hospital births in Ontario between 2012 and 2018. We used multivariable Cox proportional hazard regression and logistic regression to evaluate the relationship between prepregnancy maternal body mass index (BMI) class and stillbirth (reference was normal BMI). We treated maternal characteristics and obstetrical complications as independent covariates. We performed mediator analyses to measure the direct and indirect effects of BMI on stillbirth through major common-pathway complications. We used fully adjusted and partially adjusted models, representing the impact of maternal obesity alone and maternal obesity with other risk factors on stillbirth, respectively. RESULTS: We analyzed data on 681 178 births between 2012 and 2018, of which 1956 were stillbirths. Class I obesity was associated with an increased incidence of stillbirth (adjusted hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.35-1.78). This association was stronger for class III obesity (adjusted HR 1.80, 95% CI 1.44-2.24), and strongest for class II obesity (adjusted HR 2.17, 95% CI 1.83-2.57). Plotting point estimates for odds ratios, stratified by gestational age, showed a marked increase in the relative odds for stillbirth beyond 37 weeks' gestation for those with obesity with and without other risk factors, compared with those with normal BMI. The impact of potential mediators was minimal. INTERPRETATION: Maternal obesity alone and obesity with other risk factors are associated with an increased risk of stillbirth. This risk increases with gestational age, especially at term.
Assuntos
Obesidade Materna , Natimorto , Gravidez , Feminino , Humanos , Lactente , Natimorto/epidemiologia , Estudos Retrospectivos , Obesidade/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Accumulating studies indicate that maternal obesity is associated with the risk of cerebral palsy (CP); however, their conclusions have been inconsistent. OBJECTIVES: To quantitatively estimate the association between maternal body mass index (BMI) and CP in offspring. DATA SOURCES: PubMed, Embase and Web of Science. STUDY SELECTION AND DATA EXTRACTION: Articles published up to 18 September 2022 were searched that reported the correlation between maternal BMI and CP in children. Two reviewers independently extracted data and critically assessed articles. SYNTHESIS: Pooled relative risks (RR) and 95% confidence intervals (CI) were estimated by the random-effects model. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. RESULTS: In total, 11 articles (8,407,668 participants) were identified for inclusion in our meta-analysis. For maternal underweight, no significant association was found with CP risk (RR 1.11, 95% CI 0.90, 1.38). The risk of CP was increased by 25% (RR 1.25, 95% CI 1.06, 1.47), 38% (RR 1.38, 95% CI 1.18, 1.61) and 127% (RR 2.27, 95% CI 1.82, 2.83) for maternal overweight, obesity and obesity grade 3, respectively. In addition, we observed a positive linear dose-response relationship, with the pooled risk of cerebral palsy in offspring increasing by 3% with each unit increase in maternal BMI. CONCLUSION: This meta-analysis indicates that the risk of CP in offspring grew with maternal overweight or obesity grades increasing, and was positively correlated with maternal BMI.
Assuntos
Índice de Massa Corporal , Paralisia Cerebral , Humanos , Paralisia Cerebral/epidemiologia , Paralisia Cerebral/etiologia , Feminino , Gravidez , Criança , Fatores de Risco , Obesidade Materna/epidemiologia , Obesidade Materna/complicaçõesRESUMO
OBJECTIVE: To assess the prevalence of obesity in pregnant women in Victoria, 2010-2019. STUDY DESIGN: Retrospective cohort study; analysis of Victorian Perinatal Data Collection data. SETTING, PARTICIPANTS: Women who gave birth in seventeen Victorian Department of Health areas (eight metropolitan, nine regional), 2010-2019. MAIN OUTCOME MEASURES: Proportions of births to women with obesity (body mass index ≥ 30 kg/m2), by Department of Health area and year. RESULTS: A total of 710 364 births with records that included the mothers' BMI were recorded in Victoria during 2010-2019. The proportion of births to women with obesity rose from 19.6% (95% confidence interval [CI], 19.3-19.9%) in 2010 to 21.5% (95% CI, 21.2-21.8%) in 2019; the proportion of births to women with normal weight declined from 49.0% (95% CI, 48.6-49.4%) to 46.8% (95% CI, 46.4-47.1%). In metropolitan areas, the proportion of births to women with obesity rose from 17.7% (95% CI, 17.7-17.8%) to 19.4% (95% CI, 19.3-19.4%); in regional areas, it increased from 25.0% (95% CI, 25.0-25.1%) to 29.1% (95% CI, 29.0-29.2%). The increase in prevalence of obesity was greater among women living in the lowest socio-economic standing (Index of Relative Socio-Economic Disadvantage) quintile than for those residing in the quintile of least disadvantage (adjusted rate ratio, 2.16; 95% CI, 2.12-2.20). CONCLUSION: The proportion of births to Victorian women with obesity rose during 2010-2019, particularly in regional areas. Ensuring that regional health services are adequately resourced to meet the needs of the increasing number of women at risk of obesity during pregnancy is vital.
Assuntos
Obesidade , Humanos , Feminino , Vitória/epidemiologia , Estudos Retrospectivos , Gravidez , Adulto , Obesidade/epidemiologia , Prevalência , Complicações na Gravidez/epidemiologia , Índice de Massa Corporal , Adulto Jovem , Obesidade Materna/epidemiologiaRESUMO
BACKGROUND AND AIMS: Obesity is the most common health issue in women of reproductive age, which profoundly affects maternal-fetal health. Despite progress in understanding key inflammatory and metabolic changes, the pathogenesis of the cardiovascular phenotype of obese pregnant women remains to be fully understood. This study aimed at: (i) evaluating the changes of the renin-angiotensin system (RAS) throughout pregnancy in obese vs normal weight (control) women, and (ii) evaluating the presence of any associations between maternal hemodynamic status and RAS changes. METHODS AND RESULTS: Thirty-eight normal weight and nineteen obese pregnant women were included. Clinical assessment, blood samples and maternal hemodynamic evaluation were performed at 12, 20, 30, and 36 weeks, while ultrasound assessment was scheduled at 20, 30, and 36 weeks of gestation. Measurements of sFlt-1, PlGF, Angiotensinogen, Renin, AngII, Ang1-7, ACE and ACE2 were performed by ELISA. Our data show that normotensive obese women had lower placental blood supply, as assessed by UV-Q and UV-Q/EFW, as compared to controls, and significantly higher levels of AngII and AngII/Ang1-7 ratio, which were inversely related to placental blood supply. CONCLUSIONS: Our study shows for the first time that normotensive obese women exhibited a significant progressive increase of AngII and AngII/Ang1-7 throughout pregnancy, which were inversely related to placental blood supply as assessed by UV-Q and UV-Q/EFW. Our data shed light on the early changes in pregnant obese women and suggest that RAS dysregulation is a prerequisite rather than a consequence of hypertensive disorders of pregnancy and other maternal neonatal complications.
Assuntos
Angiotensinogênio , Obesidade Materna , Sistema Renina-Angiotensina , Renina , Feminino , Humanos , Recém-Nascido , Gravidez , Ensaio de Imunoadsorção Enzimática , Estudos Longitudinais , Placenta , Obesidade Materna/sangue , Angiotensinogênio/sangue , Renina/sangueRESUMO
INTRODUCTION: Maternal obesity is a significant risk factor for hypertensive disorders of pregnancy. High diet quality may protect against this, yet data regarding the relationship between diet quality and blood pressure among pregnant women with raised body mass index (BMI) is limited. MATERIAL AND METHODS: This is a secondary analysis (n = 543) of women with BMI ≥25 kg/m2 from two randomized controlled trials; PEARS (Pregnancy Exercise and nutrition Research Study with smartphone application support) and ROLO (Randomized cOntrol trial of LOw glycemic index diet to prevent macrosomia in euglycemic women). Blood pressure was measured at 10-18 weeks and 28 weeks of pregnancy. Mean arterial pressure was calculated as (diastolic blood pressure + 1 3 × [systolic blood pressure - diastolic blood pressure]). Diet quality was assessed using 3-day food diaries, and Alternative Healthy Eating Index for Pregnancy (AHEI-P) scores were generated, quantifying alignment of food intakes with dietary guidelines in first and early third trimesters. The cohort was divided based on AHEI-P tertiles to explore differences at an alpha significance value of <0.05. RESULTS: The mean age of the group was 32.21 ± 4.39 years with a median body mass index (BMI) of 28.13 (IQR 3.47) kg/m2. Mean arterial pressures in the first and third trimesters were 81.07 ± 9.00 mmHg and 82.33 ± 7.53 mmHg, respectively. Rates of elevated blood pressure (≥120/80 mmHg) were 22.33% in trimester 1 and 24.48% in early trimester 3. Mean AHEI-P scores in trimester 1 and early trimester 3 were 53.90 ± 10.43 and 54.05 ± 10.76, respectively. There was no correlation between AHEI-P score and blood pressure and no differences in blood pressure between AHEI-P tertiles at either timepoint (all P-values <0.05). A higher proportion of those with elevated early third trimester blood pressure had a BMI of ≥30 kg/m2 compared with those with normal blood pressure (40.31% vs 28.64%, P = 0.016). CONCLUSIONS: While diet remains an important factor in maternal health and wellbeing, we did not find a relationship between diet quality as measured by AHEI-P and blood pressure among pregnant women with BMI ≥25 kg/m2. High BMI remains a risk factor for hypertensive disorders of pregnancy.
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Pressão Sanguínea , Humanos , Feminino , Gravidez , Adulto , Índice de Massa Corporal , Sobrepeso , Dieta , Obesidade Materna , Hipertensão Induzida pela Gravidez , Obesidade/complicações , Obesidade/fisiopatologiaRESUMO
INTRODUCTION: Maternal obesity, a health condition increasingly prevalent worldwide, has been suggested to be associated with a higher risk of birth defects in offspring, whereas evidence from population-based data from China was largely lacking. Additionally, the role of gestational diabetes in the association between maternal obesity and birth defects remains unclear. We aimed to investigate the association of maternal pre-pregnancy overweight or obesity with any and different types of birth defects in offspring and the interaction between pre-pregnancy overweight or obesity and gestational diabetes. MATERIAL AND METHODS: We conducted a population-based cohort study including 257 107 singletons born between 2015 and 2021 in Longgang District, Shenzhen, China, using data from the Shenzhen Maternal and Child Health Management System. Poisson regression was conducted to estimate the associations of maternal pre-pregnancy overweight or obesity, as well as the interaction between pre-pregnancy overweight or obesity and gestational diabetes, with the risk of birth defects. Models were adjusted for maternal age at delivery, educational level, type of household registration, and gravidity. RESULTS: Maternal pre-pregnancy overweight was associated with a higher risk of any birth defect (risk ratio [RR] 1.21, 95% confidence interval [CI] 1.12 to 1.31) as well as of congenital malformations of the circulatory system (RR 1.26, 95% CI 1.12 to 1.41), eye/ear/face/neck (RR 1.42, 95% CI 1.04 to 1.94), and musculoskeletal system (RR 1.21, 95% CI 1.01 to 1.44). Maternal pre-pregnancy obesity was associated with a higher risk of any birth defect (RR 1.38, 95% CI 1.18 to 1.63) and congenital malformations of the circulatory system (RR 1.61, 95% CI 1.30 to 1.98). Infants born to overweight or obese mothers with gestational diabetes had a higher risk of congenital malformations of the circulatory system than infants born to overweight or obese mothers without gestational diabetes. CONCLUSIONS: Maternal pre-pregnancy overweight or obesity was associated with a higher risk of birth defects, particularly congenital malformations of the circulatory system, in offspring. Gestational diabetes interacts additively with pre-pregnancy overweight or obesity on modifying the risk of congenital malformations of the circulatory system. The importance of improving weight management and assessment of glucose and metabolic functions was emphasized among women planning for pregnancy who are overweight or obese.
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Diabetes Gestacional , Obesidade Materna , Lactente , Criança , Feminino , Gravidez , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Diabetes Gestacional/epidemiologia , Estudos de Coortes , Obesidade Materna/complicações , Índice de Massa Corporal , Obesidade/complicações , Obesidade/epidemiologia , Peso ao Nascer , PartoRESUMO
BACKGROUND: A substantial proportion of maternal pregnancy complications, adverse birth outcomes and neurodevelopmental delay in children may be attributable to high maternal pre-pregnancy Body Mass Index (BMI). However, BMI alone is insufficient for the identification of all at-risk mothers and children as many women with non-obesity(< 30 kg/m2) or normal weight(18.5-24.99 kg/m2) and their children may suffer from adversities. Evidence suggests that BMI-related metabolic changes during pregnancy may predict adverse mother-child outcomes better than maternal anthropometric BMI. METHODS: In a cohort of 425 mother-child dyads, we identified maternal BMI-defined metabolome based on associations of 95 metabolic measures measured three times during pregnancy with maternal pre-pregnancy BMI. We then examined whether maternal BMI-defined metabolome performed better than anthropometric BMI in predicting gestational diabetes, hypertensive disorders, gestational weight gain (GWG), Caesarian section delivery, child gestational age and weight at birth, preterm birth, admission to neonatal intensive care unit (NICU), and childhood neurodevelopment. Based on metabolic measures with the highest contributions to BMI-defined metabolome, including inflammatory and glycolysis-related measures, fatty acids, fluid balance, ketone bodies, lipids and amino acids, we created a set of maternal high BMI-related polymetabolic risk scores (PMRSs), and in an independent replication cohort of 489 mother-child dyads tested their performance in predicting the same set of mother-child outcomes in comparison to anthropometric BMI. RESULTS: BMI-defined metabolome predicted all of the studied mother-child outcomes and improved their prediction over anthropometric BMI, except for gestational hypertension and GWG. BMI-related PMRSs predicted gestational diabetes, preeclampsia, Caesarian section delivery, admission to NICU, lower gestational age at birth, lower cognitive development score of the child, and improved their prediction over anthropometric BMI. BMI-related PMRSs predicted gestational diabetes, preeclampsia, Caesarean section delivery, NICU admission and child's lower gestational age at birth even at the levels of maternal non-obesity and normal weight. CONCLUSIONS: Maternal BMI-defined metabolome improves the prediction of pregnancy complications, birth outcomes, and neurodevelopment in children over anthropometric BMI. The novel, BMI-related PMRSs generated based on the BMI-defined metabolome have the potential to become biomarkers identifying at-risk mothers and their children for timely targeted interventions even at the level of maternal non-obesity and normal weight.