Maternal Obesity Affects Inflammatory and Iron Indices in Umbilical Cord Blood

Abstract

Objective To determine the impact of maternal obesity and gestational weight gain across pregnancy on fetal indices of inflammation and iron status. Study design Eighty-five healthy term newborns delivered via elective cesarean were categorized by 2 maternal body mass index (BMI) thresholds; above or below 30 kg/m2 or above or below 35 kg/m2. Umbilical cord plasma levels of C-reactive protein, interleukin (IL)-6, tumor necrosis factor (TNF)-α, ferritin, and hepcidin were assayed. Cytokines released by phytohemagglutinin-stimulated umbilical cord mononuclear cells (MNCs) were assayed. Results Maternal class II obesity, defined as BMI of 35 kg/m2 and above, predicted higher C-reactive protein and TNF-α in umbilical cord plasma (P< .05 for both), and also proinflammatory cytokines (IL-1β, IL-6, and TNF-α) from stimulated MNC (P < .05 for all). The rise in plasma TNF-α and MNC TNF-α was not linear but occurred when the threshold of BMI 35 kg/m2 was reached (P < .005, P < .06). Poorer umbilical cord iron indices were associated with maternal obesity. When ferritin was low, IL-6 was higher (P < .04), but this relationship was present primarily when maternal BMI exceeded 35 kg/m2 (P < .03). Ferritin was correlated with hepcidin (P < .0001), but hepcidin was unrelated to either maternal BMI or inflammatory indices. Conclusions Class II obesity and above during pregnancy is associated with fetal inflammation in a threshold fashion. Although maternal BMI negatively impacted fetal iron status, hepcidin, related to obesity in adults, was related to iron status and not obesity in fetuses. Pediatricians should be aware of these relationships.

Effects of maternal obesity on placental function and fetal development

“…Although the concept of low-grade inflammation with obesity is widely accepted, an increased pro-inflammatory cytokine profile in obese mothers has not been consistently reported and appears to be modulated with advancing gestation (Friis et al 2013; Stewart et al 2007; Christian and Porter, 2014). A significant pro-inflammatory activation may not occur in the developing human fetus of obese mothers (Aye et al 2014b; Pantham et al 2015) or may be present only in severe obesity (body mass index >35 kg/m 2 ) (Dosch et al 2016). However, even if direct fetal exposure to maternal cytokines may be limited, cytokines in the maternal circulation have been proposed to modulate placental growth and function, which in turn impacts fetal development.…”

Impact of pregravid obesity on maternal and fetal immunity: Fertile grounds for reprogramming

“…Very high maternal BMI (>35) has been associated with elevated systemic levels of inflammatory mediators, notably TNF and C-reactive protein (CRP) in the cord plasma. 81,82 In addition to these canonical inflammatory markers, maternal BMI is also a strong indicator of cord blood levels of malondialdehyde and NO, contributing to increased oxidative stress in the newborn. 83 In agreement with this hypothesis, transcriptional studies in cord blood have demonstrated elevated expression of genes involved in the cellular response to oxidative stress and inflammatory signaling with high maternal BMI, independent of offspring adiposity.…”

“…Poor ex vivo monocyte responses in the offspring with pregravid obesity could potentially be tied to an altered inflammatory intrauterine environment. Very high maternal BMI (>35) has been associated with elevated systemic levels of inflammatory mediators, notably TNFα and C‐reactive protein (CRP) in the cord plasma . In addition to these canonical inflammatory markers, maternal BMI is also a strong indicator of cord blood levels of malondialdehyde and NO, contributing to increased oxidative stress in the newborn .…”

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

“…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 .…”