Abstract
Mechanistic pathways linking maternal polyunsaturated fatty acid (PUFA) status with gestational length are poorly delineated. This study examined whether inflammation and sleep quality serve as mediators, focusing on the antiinflammatory ω-3 docosahexaenoic acid (DHA; 22:6n3) and proinflammatory ω-6 arachidonic acid (AA; 20:4n6). Pregnant women (n = 135) provided a blood sample and completed the Pittsburgh Sleep Quality Index (PSQI) at 20–27 weeks gestation. Red blood cell (RBC) fatty acid levels were determined by gas chromatography and serum inflammatory markers [interleukin (IL)-6, IL-8, tumor necrosis factor-α, IL-1β, and C-reactive protein] by electrochemiluminescence using high sensitivity kits. Both higher serum IL-8 (95% CI = 0.10,3.84) and poor sleep (95% CI = 0.03,0.28) served as significant mediators linking lower DHA:AA ratios with shorter gestation. Further, a serial mediation model moving from the DHA:AA ratio → sleep → IL-8 → length of gestation was statistically significant (95% CI = 0.02, 0.79). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. No interactions with race were observed in relation to length of gestation as a continuous variable. However, a significant interaction between race and the DHA:AA ratio in predicting preterm birth was observed (p = 0.049); among African Americans only, odds of preterm birth decreased as DHA:AA increased (p = 0.048). These data support a role for both inflammatory pathways and sleep quality in linking less optimal RBC PUFA status with shorter gestation in African American and European American women and suggest that African-Americans have greater risk for preterm birth in the context of a low DHA:AA ratio.
Highlights
It is well established that long chain polyunsaturated fatty acids (LC-PUFAs), the ω-3 docosahexanoic acid (DHA; 22:6n-3), are critical to fetal growth, neural and retinal development
In this study of 135 pregnant women assessed in mid-gestation, both serum inflammatory markers and sleep quality served as mediators linking red blood cell (RBC) PUFA status with length of gestation
Higher serum IL-8 significantly mediated the association between higher arachidonic acid (AA) and a lower DHA:AA ratio with shorter gestation
Summary
It is well established that long chain polyunsaturated fatty acids (LC-PUFAs), the ω-3 docosahexanoic acid (DHA; 22:6n-3), are critical to fetal growth, neural and retinal development. Other meta-analyses of studies in low as well as high-risk populations indicate that maternal consumption of LC-PUFAs, lower DHA, predicts shorter length of gestation and/or risk for preterm birth [7,8,9,10] This effect is supported in a phase III, double-blind RCT of 350 women which demonstrated that supplementation with 600 mg/d of DHA in the last half of pregnancy resulted in longer gestation and greater infant size (birth weight, length, and head circumference)[11]. Our prior data demonstrate an association between poor sleep quality during pregnancy and risk for shorter gestation which was mediated by elevations in serum levels of the proinflammatory cytokine interleukin(IL)-8 [25] In these prior analyses, effects were driven by African American women. Given racial disparities in preterm birth, and our prior data demonstrating differential effects by race, we examined effects of race within these models
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