Maternal inflammatory diet and adverse pregnancy outcomes: Circulating cytokines and genomic imprinting as potential regulators?

Abstract

Excessive inflammation during pregnancy alters homeostatic mechanisms of the developing fetus and has been linked to adverse pregnancy outcomes. An anti-inflammatory diet could be a promising avenue to combat the pro-inflammatory state of pregnancy, particularly in obese women, but we lack mechanistic data linking this dietary pattern during pregnancy to inflammation and birth outcomes. In an ethnically diverse cohort of 1057 mother-child pairs, we estimated the relationships between dietary inflammatory potential [measured via the energy-adjusted dietary inflammatory index (E-DII™)] and birth outcomes overall, as well as by offspring sex and maternal pre-pregnancy body mass index (BMI). In a subset of women, we also explored associations between E-DII, circulating cytokines (n = 105), and offspring methylation (n = 338) as potential modulators of these relationships using linear regression. Adjusted regression models revealed that women with pro-inflammatory diets had elevated rates of preterm birth among female offspring [β = -0.22, standard error (SE) = 0.07, P<0.01], but not male offspring (β=0.09, SE = 0.06, P<0.12) (P = 0.003). Similarly, we observed pro-inflammatory diets were associated with higher rates of caesarean delivery among obese women (β = 0.17, SE = 0.08, P = 0.03), but not among women with BMI <25 kg/m (P = 0.02). We observed consistent inverse associations between maternal inflammatory cytokine concentrations (IL-12, IL-17, IL-4, IL-6, and TNFα) and lower methylation at the MEG3 regulatory sequence (P<0.05); however, results did not support the link between maternal E-DII and circulating cytokines. We replicate work by others on the association between maternal inflammatory diet and adverse pregnancy outcomes and provide the first empirical evidence supporting the inverse association between circulating cytokine concentrations and offspring methylation.

Associations between maternal cytokine levels during gestation and measures of child cognitive abilities and executive functioning

“…Continued work across species will be useful in clarifying the role of specific inflammatory markers on child cognitive ability and executive functioning. Studies that elucidate the down-stream factors contributing to prenatal inflammation are needed, as well as studies examining potential mechanisms [e.g., epigenetic alterations (McCullough et al, (2017)] that may help explain the link between immune activity and measures of cognitive ability and executive functioning. To the extent that early child cognitive and executive functioning abilities are a harbinger for physical and mental health outcomes over the life-course, understanding the role of maternal gestational immune activity could be useful for early identification and remediation of long-term deleterious outcomes with high societal impact.…”

Intergenerational associations of dietary inflammatory index with birth outcomes and weight status at age 5 and 9: Results from the Lifeways cross‐generation cohort study

“…In our study, higher maternal E‐DII scores (mean E‐DII of 0.42, range of −4.39 to 5.52) were associated with higher risk of LBW. McCullough et al examined maternal DII (median E‐DII of −1.37, range of −5.00 to 4.96) and birth outcomes in a multi‐ethnic population (43% African‐American, 34% White and 23% Hispanic) but found no association with birthweight, only with adverse pregnancy outcomes (higher caesarean delivery rate in mothers with obesity). Conversely in Project Viva, a cohort comprising mother–child pairs (70.6% White race, mean DII of −2.6 ± 1.4), a pro‐inflammatory diet in pregnancy was associated with LBW, consistent with our findings, and also infant adiposity.…”

“…Recent data from the Healthy Start Study showed that higher DII scores in mothers with obesity were associated with increased neonatal adiposity . Ethnic diversity and maternal weight status during pregnancy may contribute to the disparity between studies. Black race, Hispanic ethnicity and higher maternal BMI were associated with a more higher E‐DII scores in both studies, while older maternal age and higher household income and education were associated with lower E‐DII score, consistent with our results.…”

“…In children, CRP concentrations predicted annual BMI‐for‐age z score gain during childhood . There is also evidence that prenatal factors, including maternal weight and nutrition, can modify placental and fetal growth and, therefore, predispose children to developing chronic diseases, such as obesity, in later life …”

“…such as obesity, in later life. 8,9 The literature-derived Dietary Inflammation Index (DII ® ) was developed to characterize the inflammatory potential of an individual's diet on a spectrum from anti-to pro-inflammatory. 10 The DII, which is validated against several inflammatory biomarkers in numerous populations, 11,12 including an Irish adult cohort, 13 has been associated with a range of health outcomes including cancer, asthma, anthropometric measures, cardiometabolic health, metabolic syndrome (MetS) and adverse mental health outcomes.…”