Maternal obesity alters immune cell frequencies and responses in umbilical cord blood samples

Wilson, Randall M.; Marshall, Nicole; Jeske, Daniel R.; Purnell, Jonathan Q.; Thornburg, Kent L.; Messaoudi, Ilhem

doi:10.1111/pai.12387

Cited by 71 publications

(100 citation statements)

References 22 publications

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“…The percentage change in estimates between models using the adult and cord blood reference panels was under 10% at 14/15 sites using the Andrews Table S8). Although maternal BMI was not associated with estimated cell proportions in our data, others have observed that maternal BMI is associated with cord blood cellular heterogeneity (31,32), in addition, some random variability in cell distribution across the range of maternal BMI can be expected. Therefore, we believe that adjustment is appropriate and indeed necessary.…”

Section: à7contrasting

confidence: 85%

Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the Pregnancy and Childhood Epigenetics (PACE) consortium

Sharp

Salas²,

Monnereau³

et al. 2017

Preprint

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Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m 2 ), P < 1.06 Â 10 À7 ) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for a6causal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.

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Section: à7contrasting

confidence: 85%

Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the Pregnancy and Childhood Epigenetics (PACE) consortium

Sharp

Salas²,

Monnereau³

et al. 2017

Preprint

View full text Add to dashboard Cite

show abstract

“…Future studies will need to focus on epigenetic changes within individual immune cell populations, as important changes in small populations may not be apparent when analyzing total leukocytes. Specifically, it might be interesting to examine epigenetic changes in monocytes or CD4 T helper cells as we have shown recently a dampened response by monocytes and myeloid dendritic cells stimulated by TL4 or TLR1&2 agonists and a reduction in IL-4 production by CD4 T cells (110). …”

Section: Resultsmentioning

confidence: 99%

The impact of maternal obesity during pregnancy on offspring immunity

Wilson

Messaoudi

2015

Molecular and Cellular Endocrinology

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In the United States, approximately 64% of women of childbearing age are either overweight or obese. Maternal obesity during pregnancy is associated with a greater risk for adverse maternalfetal outcomes. Adverse health outcomes for the offspring can persist into adulthood, increasing the incidence of several chronic conditions including cardiovascular disease, diabetes, and asthma. Since these diseases have a significant inflammatory component, these observations are indicative of perturbation of the normal development and maturation of the immune system of the offspring in utero. This hypothesis is strongly supported by data from several rodent studies. Although the mechanisms of these perturbations are not fully understood, it is thought that increased placental inflammation due to obesity may directly affect neonatal development through alterations in nutrient transport. In this review we examine the impact of maternal obesity on the neonatal immune system, and potential mechanisms for the changes observed.

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“…Maternal obesity leads to changes in immune cell counts –including eosinophils and monocytes, the levels of inflammatory cytokines (i.e. interleukin [IL]-1β, IL-6, tumor necrosis factor [TNF]-α, or interferon [IFN]-α2) 22,23 , and lipid profiles in cord blood or early post-natal life 25 . Moreover, maternal obesity may lead to metabolic and oxidative alterations in the placenta and the fetus 24 , and increased leptin level and insulin resistance in newborns 26 .…”

Section: Maternal Obesity During Pregnancy and Weight Gain In Early Pmentioning

confidence: 99%

The effect of obesity, weight gain, and weight loss on asthma inception and control

Forno

Celedón

2017

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of the review There is ample and growing evidence that obesity increases the risk of asthma and morbidity from asthma. Here we review recent clinical evidence supporting a causal link between obesity and asthma, and the mechanisms that may lead to “obese asthma”. Recent findings While in some children obesity and asthma simply co-occur, those with “obese asthma” have increased asthma severity, lower quality of life, and reduced medication response. Underlying mechanistic pathways may include anatomical changes of the airways such as obstruction and dysanapsis; systemic inflammation; production of adipokines; impaired glucose-insulin metabolism; altered nutrient levels; genetic and epigenetic changes; and alterations in the airway and/or gut microbiome. A few small studies have shown that weight loss interventions may lead to improvements in asthma outcomes, but thus far research on therapeutic interventions for these children has been limited. Summary Obesity increases the risk of asthma –and worsens asthma severity or control– via multiple mechanisms. “Obese asthma” is a complex, multifactorial phenotype in children. Obesity and its complications must be managed as part of the treatment of asthma in obese children.

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Maternal obesity alters immune cell frequencies and responses in umbilical cord blood samples

Abstract: These results support the hypothesis that maternal obesity influences programming of the neonatal immune system, providing a potential link to increased incidence of chronic inflammatory diseases such as asthma and cardiovascular disease in the offspring.

Cited by 71 publications

References 22 publications

Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the Pregnancy and Childhood Epigenetics (PACE) consortium

Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: Findings from the Pregnancy and Childhood Epigenetics (PACE) consortium

The impact of maternal obesity during pregnancy on offspring immunity

The effect of obesity, weight gain, and weight loss on asthma inception and control

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