Omega-3 Fatty Acid Supplementation, Pro-Resolving Mediators, and Clinical Outcomes in Maternal-Infant Pairs

Tara M Nordgren, Ann Anderson Berry, Matthew Van Ormer, Samuel Zoucha, Elizabeth Elliott, Rebecca Johnson, Elizabeth McGinn, Caleb Cave, Katherine Rilett, Kara Weishaar, Sai Sujana Maddipati, Harriet Appeah, Corrine Hanson, Tara M Nordgren, Ann Anderson Berry, Matthew Van Ormer, Samuel Zoucha, Elizabeth Elliott, Rebecca Johnson, Elizabeth McGinn, Caleb Cave, Katherine Rilett, Kara Weishaar, Sai Sujana Maddipati, Harriet Appeah, Corrine Hanson

Abstract

Omega (n)-3 fatty acids are vital to neonatal maturation, and recent investigations reveal n-3 fatty acids serve as substrates for the biosynthesis of specialized pro-resolving lipid mediators (SPM) that have anti-inflammatory and immune-stimulating effects. The role SPM play in the protection against negative maternal-fetal health outcomes is unclear, and there are no current biomarkers of n-3 fatty acid sufficiency. We sought to ascertain the relationships between n-3 fatty acid intake, SPM levels, and maternal-fetal health outcomes. We obtained n-3 fatty acid intake information from 136 mothers admitted for delivery using a food frequency questionnaire and measured docosahexaenoic acid (DHA)-derived SPMs resolvin D1 (RvD1) and RvD2 in maternal and cord plasma. We found significantly elevated SPM in maternal versus cord plasma, and increased SPM levels were associated with at-risk outcomes. We also identified that increased DHA intake was associated with elevated maternal plasma RvD1 (p = 0.03; R² = 0.18) and RvD2 (p = 0.04; R² = 0.20) in the setting of neonatal intensive care unit (NICU) admission. These findings indicate that increased n-3 fatty acid intake may provide increased substrate for the production of SPM during high-risk pregnancy/delivery conditions, and that increased maternal plasma SPM could serve as a biomarker for negative neonatal outcomes.

Keywords: docosahexaenoic acid (DHA); fetal health; omega-3 fatty acid; pregnancy; resolvins; specialized pro-resolving lipid mediator (SPM).

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Resolvin D1 (RvD1) and Resolvin D2 (RvD2) levels in maternal and cord blood plasma. Enzyme immunoassays were performed on maternal and cord blood plasma samples collected upon admission for delivery and at birth, respectively. (A) RvD1 levels in maternal and cord blood plasma; (B) RvD2 levels in maternal and cord blood plasma; (C) comparison of maternal RvD1 and RvD2 plasma levels; (D) comparison of cord RvD1 and RvD2 plasma levels.
Figure 2
Figure 2
Comparison of maternal and cord blood plasma RvD1 and RvD2 levels and infant NICU admission at birth. Samples were stratified based on infant NICU admission at birth (yes/no) and maternal and cord blood plasma RvD1 and RvD2 levels were compared. (A) Maternal RvD1 levels; (B) maternal RvD2 levels; (C) cord RvD1 levels; (D) cord RvD2 levels. n.s.: no significant difference.
Figure 3
Figure 3
Comparison of maternal and cord blood plasma RvD1 and RvD2 levels and gestational age at delivery. Maternal and cord blood RvD1 and RvD2 levels were separated into infants delivering at less than 36 weeks estimated gestational age versus infants delivered at greater than or equal to 36 weeks estimated gestational age and compared. (A) Maternal RvD1 levels; (B) maternal RvD2 levels; (C) cord RvD1 levels; (D) cord RvD2 levels. n.s.: no significant difference.
Figure 4
Figure 4
Receiver-operating characteristic (ROC) curves of sensitivity and specificity of maternal RvD1 and RvD2 in discriminating preterm birth, defined as infants delivered at less than 36 weeks estimated gestational age versus infants delivered at greater than or equal to 36 weeks gestational age (A), and NICU admission (B) outcomes.
Figure 5
Figure 5
Relationship between DHA intake and maternal RvD1 and RvD2 plasma levels. Maternal RvD1 and RvD2 plasma levels were stratified based on infant NICU admission upon delivery and compared with DHA intake. (A) Linear regressions of maternal RvD1 levels and DHA intake in mothers with (A) and without (B) infant NICU admission upon delivery; Linear regression of maternal RvD2 levels and DHA intake in mothers with (C) and without (D) NICU admission upon delivery.

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