Maternal obesity and the impact of associated early-life inflammation on long-term health of offspring

Abstract

The prevalence of obesity is increasingly common in the United States, with ~25% of women of reproductive age being overweight or obese. Metaflammation, a chronic low grade inflammatory state caused by altered metabolism, is often present in pregnancies complicated by obesity. As a result, the fetuses of mothers who are obese are exposed to an in-utero environment that has altered nutrients and cytokines. Notably, both human and preclinical studies have shown that children born to mothers with obesity have higher risks of developing chronic illnesses affecting various organ systems. In this review, the authors sought to present the role of cytokines and inflammation during healthy pregnancy and determine how maternal obesity changes the inflammatory landscape of the mother, leading to fetal reprogramming. Next, the negative long-term impact on offspring’s health in numerous disease contexts, including offspring’s risk of developing neuropsychiatric disorders (autism, attention deficit and hyperactive disorder), metabolic diseases (obesity, type 2 diabetes), atopy, and malignancies will be discussed along with the potential of altered immune/inflammatory status in offspring as a contributor of these diseases. Finally, the authors will list critical knowledge gaps in the field of developmental programming of health and diseases in the context of offspring of mothers with obesity, particularly the understudied role of hematopoietic stem and progenitor cells.

Obesidad pregestacional y alteraciones del parto

“…Existe evidencia que señala que los riesgos de la cesárea son mayores y más complejos en las embarazadas obesas. Aparte de presentar mayores probabilidades de indicación de interrupción del embarazo por vía abdominal, también tienen mayor riesgo de complicaciones postoperatorias asociadas a la obesidad (por ejemplo, preeclampsia) (21)(22)(23) . Aunque la cesárea es un buen indicador de los posibles efectos de la obesidad sobre las alteraciones del parto, la información que puede suministrar debe ser analizada cuidadosamente, ya que puede ser afectada por múltiples factores.…”

Role of Obesity in Female Reproduction

“…There is concern that an altered inflammatory state can impact the growing fetus indirectly by altering a variety of placental functions (e.g., trophoblast invasion or nutrient transport) 98 . Aye et al found that increased maternal BMI was associated with activation of placental p38-MAPK and STAT signaling, demonstrating that inflammation associated with maternal obesity is regulated by altered placental function 99 .…”

Identifying of immune‐associated genes for assessing the obesity‐associated risk to the offspring in maternal obesity: A bioinformatics and machine learning

“…It is increasingly acknowledged as an early‐life factor that influences offspring health 3 . Mothers with pre‐pregnancy obesity tend to have high circulating levels of pro‐inflammatory markers/cytokines, such as IL‐8, IL‐6, CRP, TNF‐α, IFN‐γ, and altered adipokine level 4 . Human data have revealed that the activated pro‐inflammatory state during pregnancy is linked to adverse health outcomes in offspring, including childhood obesity 4 .…”

“… 3 Mothers with pre‐pregnancy obesity tend to have high circulating levels of pro‐inflammatory markers/cytokines, such as IL‐8, IL‐6, CRP, TNF‐α, IFN‐γ, and altered adipokine level. 4 Human data have revealed that the activated pro‐inflammatory state during pregnancy is linked to adverse health outcomes in offspring, including childhood obesity. 4 Animal experiments have demonstrated that fetal inflammation induced by maternal obesity significantly contributes to the promoting adipogenesis and increasing adiposity in the offspring.…”