UNASSIGNED: Maternal obesity poses risks for both mother and offspring during pregnancy, with underlying mechanisms remaining largely unexplored. Obesity is associated with microbial gut dysbiosis and low-grade inflammation, and also the diet has a major impact on these parameters. This study aimed to investigate how maternal obesity and diet contribute to changes in immune responses, exploring potential associations with gut microbiota dysbiosis and adverse pregnancy outcomes in mice.
UNASSIGNED: Before mating, C57BL/6 mice were assigned to either a high-fat-diet (HFD) or low-fat-diet (LFD) to obtain obese (n=17) and lean (n=10) mice. To distinguish between the effects of obesity and diet, 7 obese mice were switched from the HFD to the LFD from day 7 until day 18 of pregnancy (\"switch group\"), which was the endpoint of the study. T helper (Th) cell subsets were studied in the spleen, mesenteric lymph nodes (MLN) and Peyer\'s patches (PP), while monocyte subsets and activation status were determined in maternal blood (flow cytometry). Feces were collected before and during pregnancy (day 7,14,18) for microbiota analysis (16S rRNA sequencing). Pregnancy outcome included determination of fetal and placental weight.
UNASSIGNED: Obesity increased splenic Th1 and regulatory T cells, MLN Th1 and PP Th17 cells and enhanced IFN-γ and IL-17A production by splenic Th cells upon ex vivo stimulation. Switching diet decreased splenic and PP Th2 cells and classical monocytes, increased intermediate monocytes and activation of intermediate/nonclassical monocytes. Obesity and diet independently induced changes in the gut microbiota. Various bacterial genera were increased or decreased by obesity or the diet switch. These changes correlated with the immunological changes. Fetal weight was lower in the obese than the lean group, while placental weight was lower in the switch than the obese group.
UNASSIGNED: This study demonstrates that obesity and diet independently impact peripheral and intestinal immune responses at the end of pregnancy. Simultaneously, both factors affect specific bacterial gut genera and lead to reduced fetal or placental weight. Our data suggest that switching diet during pregnancy to improve maternal health is not advisable and it supports pre/probiotic treatment of maternal obesity-induced gut dysbiosis to improve maternal immune responses and pregnancy outcome.

BACKGROUND: Shared decision-making supports women\'s choices in pregnancy. Women with high body mass index (≥35 kg/m2) experience a high rate of interventions in pregnancy, labour, and birth, providing an opportunity for clinicians to implement shared decision-making in practice. However, weight stigma may limit women\'s opportunities for shared decision-making.
OBJECTIVE: To understand how pregnant women with high body mass index perceive their involvement in antenatal decision-making, including whether weight stigma influences their experience.
METHODS: Women with high body mass index were recruited via purposive sampling from two sites in Melbourne, Australia. Semi-structured interviews were audio-recorded, transcribed, and analysed using reflexive thematic analysis.
RESULTS: Ten pregnant women consented to participate. Three themes and six sub-themes were identified. These were: 1) Trusting the system, 2) Who takes the lead?, and 3) Defying disease.
CONCLUSIONS: Shared decision-making is limited for women with high body mass index in antenatal care, and weight stigma is experienced by women. Clinical practice recommendations relating to excess weight have the potential to further limit women\'s involvement in decision-making if adequate support is not provided to ensure women\'s understanding and involvement in care.
CONCLUSIONS: Women\'s involvement in care is a central component of shared decision-making and it is currently limited for women with high body mass index. Transparency regarding the rationale for recommendations is required, and further work must be done to address the influence and impact of weight stigma on the care of women with high body mass index.

OBJECTIVE: To assess the prevalence of obesity in pregnant women in Victoria, 2010-2019.
METHODS: Retrospective cohort study; analysis of Victorian Perinatal Data Collection data.
METHODS: Women who gave birth in seventeen Victorian Department of Health areas (eight metropolitan, nine regional), 2010-2019.
METHODS: 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).
CONCLUSIONS: 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.

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.

The prevalence of overweight and obese people worldwide has dramatically increased in the last decades and is yet to peak. At the same time and partly due to obesity and associated assisted reproduction, twinning rates showed a clear rise in the last years. Adverse fetomaternal outcomes are known to occur in singleton and twin pregnancies in overweight and obese women. However, the impact of the obesity levels as defined by the World Health Organization on the outcomes of twin pregnancies has not been thoroughly studied. Therefore, the purpose of this study is to examine how maternal overweight, and the level of obesity affect fetomaternal outcomes in twin pregnancies, hypothesizing a higher likelihood for adverse outcomes with overweight and each obesity level. This is a retrospective cohort study with 2,349 twin pregnancies that delivered at the Buergerhospital Frankfurt, Germany between 2005 and 2020. The mothers were divided into exposure groups depending on their pre-gestational body mass index; these were normal weight (reference group), overweight and obesity levels I, II, and III. A multivariate logistic regression analysis was performed to assess the influence of overweight and obesity on gestational diabetes mellitus, preeclampsia, postpartum hemorrhage, intrauterine fetal death, and a five-minutes Apgar score below seven. The adjusted odds ratio for gestational diabetes compared to normal weight mothers were 1.47, 2.79, 4.05, and 6.40 for overweight and obesity levels I, II and III respectively (p = 0.015 for overweight and p < 0.001 for each obesity level). Maternal BMI had a significant association with the risk of preeclampsia (OR 1.04, p = 0.028). Overweight and obesity did not affect the odds of postpartum hemorrhage, fetal demise, or a low Apgar score. While maternal overweight and obesity did not influence the fetal outcomes in twin pregnancies, they significantly increased the risk of gestational diabetes and preeclampsia, and that risk is incremental with increasing level of obesity.

Previous studies reporting the association between gut microbiota dysbiosis and maternal obesity were mostly confined at the phylum level or at postpartum period. This study aimed to investigate the dynamic changes in gut microbial communities associated with maternal obesity at different time points of pregnancy. We performed 16S rRNA gene V3-V4 amplicon sequencing on stool samples from 110 women in all three trimesters and 1-month postpartum. Maternal gut microbial communities associated with maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) were explored. The influence of maternal obesity on gut microbiota trajectories was determined based on longitudinal shifts in community clusters across the trimesters. The richness index of alpha diversity decreased with the progression of pregnancy, particularly in women with excessive GWG. The evenness index in 2nd trimester was found inversely associated with GWG. Various taxonomic differences in 1st trimester were associated with excessive GWG, whereas limited taxonomic differences in 2nd and 3rd trimesters were associated with pre-pregnancy BMI or GWG. Meanwhile, the gut microbiota trajectory with especially depleted genus Faecalibacterium in 1st trimester was associated with excessive GWG (adjusted odds ratio 5.7, 95% confidence interval 1.2-28.1). Moreover, the longitudinal abundances of genus Lachnospiraceae ND3007 group across gestations were depleted in women with overweight/obese pre-pregnancy BMI, while genus Bifidobacterium enriched in women with excessive GWG. Our study shows that dysbiosis of the gut microbiota in early pregnancy may have a significant impact on excess GWG. The abundance of the genus Faecalibacterium in 1st trimester may be a potential risk factor. Clinical trial number: NCT03785093 (https://classic.clinicaltrials.gov/ct2/show/NCT03785093).

Diet-induced obesity reduces oocyte quality mainly by impacting oocyte mitochondrial functions. Moreover, maternal obesity is associated with mitochondrial dysfunction in oocytes of their adult offspring. However, these effects were reported only in fully grown oocytes, mainly in the form of abnormal mitochondrial ultrastructure. It is unknown if obesogenic (OB) diets or maternal obesity already impact the primordial and preantral follicles. Considering the long duration and dynamics of folliculogenesis, determining the stage at which oocytes are affected and the extent of the damage is crucial for optimal reproductive management of obese patients and their daughters. Potential interaction between maternal and offspring diet effects are also not described, yet pivotal in our contemporary society. Therefore, here we examined the impact of OB diets on oocyte mitochondrial ultrastructure in primordial and activated preantral follicles in offspring from diet-induced obese or lean mothers. We used an outbred Swiss mouse model to increase the pathophysiological relevance to humans. Female mice were fed control or OB diets for 7 weeks, then mated with control males. Their female offspring were fed control or OB diets after weaning for 7 weeks (2-by-2 factorial design). Adult offspring ovarian sections were examined using transmission electron microscopy. We characterised and classified unique features of oocyte mitochondrial ultrastructure in the preantral follicles. An increase in mitochondrial matrix density was the most predominant change during follicle activation in secondary follicles, a feature that is linked with a higher mitochondrial activity. Maternal obesity increased mitochondrial density already in the primordial follicles suggesting an earlier increase in bioenergetic capacity. Maternal obesity did not induce abberant ultrastructure (abnormalities and defects) in primordial or preantral follicles. In contrast, offspring OB diet increased mitochondrial abnormalities in the primordial follicles. Further investigation of the consequences of these changes on oocyte metabolic regulation and stress levels during folliculogenesis is needed.

Maternal obesity and/or Western diet (WD) is associated with an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven, in part, by the dysregulation of the early life microbiome. Here, using a mouse model of WD-induced maternal obesity, we demonstrate that exposure to a disordered microbiome from WD-fed dams suppressed circulating levels of endogenous ligands of the aryl hydrocarbon receptor (AHR; indole, indole-3-acetate) and TMAO (a product of AHR-mediated transcription), as well as hepatic expression of Il10 (an AHR target), in offspring at 3 weeks of age. This signature was recapitulated by fecal microbial transfer from WD-fed pregnant dams to chow-fed germ-free (GF) lactating dams following parturition and was associated with a reduced abundance of Lactobacillus in GF offspring. Further, the expression of Il10 was downregulated in liver myeloid cells and in LPS-stimulated bone marrow-derived macrophages (BMDM) in adult offspring, suggestive of a hypo-responsive, or tolerant, innate immune response. BMDMs from adult mice lacking AHR in macrophages exhibited a similar tolerogenic response, including diminished expression of Il10. Overall, our study shows that exposure to maternal WD alters microbial metabolites in the offspring that affect AHR signaling, potentially contributing to innate immune hypo-responsiveness and progression of MASLD, highlighting the impact of early life gut dysbiosis on offspring metabolism. Further investigations are warranted to elucidate the complex interplay between maternal diet, gut microbial function, and the development of neonatal innate immune tolerance and potential therapeutic interventions targeting these pathways.

Maternal gestational obesity is related to risk of obesity in the child. This risk may be in part mediated by altered child temperament, which can affect mother-child interactions, including feeding and soothing behaviors that affect obesity risk. Our objective was to examine the association between maternal pre-pregnancy BMI and child zBMI and determine if child temperament, specifically positive Affectivity/Surgency, mediates this association. Using conditional process modeling, we analyzed data from 408 mother-child dyads enrolled in the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Child temperament was assessed at 3 years of age via a parent report measure, the Child Behavior Questionnaire (CBQ), and child zBMI was calculated from in-person measurements of child height and weight at 4-5 years of age. Bivariate correlations showed that there was a significant positive correlation between zBMI and Surgency (r = 0.11, p = 0.03), and zBMI was also correlated with maternal pre-pregnancy BMI (r = 0.12, p = 0.02). Multivariable regression revealed that maternal pre-pregnancy BMI (adjusted β = 0.15, 95% confidence interval [CI]; 0.00-0.05, p = 0.02) and Surgency scores (adjusted β = 0.14, 95% CI; 0.02-0.28, p = 0.03) were associated with higher child zBMI at 4-5 years of age. Mediation analysis showed that Surgency mediated the association between pre-pregnancy BMI and child zBMI. Our models controlled for maternal gestational weight gain, gestational diabetes, socioeconomic status, maternal anxiety and depression, and gestational age at birth. Overall, maternal pre-pregnancy BMI was positively associated with child zBMI, and this association was mediated by higher child Surgency scores.

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.
CONCLUSIONS: 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.