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Generating a Reproducible Model of Mid-Gestational Maternal Immune Activation using Poly(I:C) to Study Susceptibility and Resilience in Offspring
Published on: August 17, 2022
Developmental programming for allergy: a secondary analysis of the Mothers, Omega-3, and Mental Health Study
Vivian C Romero1, Emily C Somers, Valerie Stolberg
1Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Michigan Medical School, Ann Arbor, MI, USA.
Insights
Prenatal omega-3 fatty acid supplementation, including eicosapentaenoic acid and docosahexaenoic acid, lowered T helper 2/T helper 1 chemokine ratios in newborns. Cesarean delivery was linked to a higher T helper 2 bias at birth.
Area of Science:
- Immunology
- Perinatal Medicine
- Nutritional Science
Background:
- Fetal immune system development, particularly T helper cell pathways, is crucial for allergy predisposition.
- Elevated cord blood T helper 2 (Th2) to T helper 1 (Th1) ratios are associated with an increased risk of developing allergic diseases.
- Understanding factors influencing fetal immune programming, such as maternal supplementation and delivery mode, is vital for allergy prevention.
Purpose of the Study:
- To investigate if prenatal supplementation with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) alters cord blood Th2/Th1 chemokine ratios.
- To examine the influence of delivery mode (vaginal vs. Cesarean) on cord blood Th2/Th1 chemokine profiles.
Main Methods:
- Secondary analysis of a randomized placebo-controlled trial involving 126 participants.
- Cord plasma from 98 newborns analyzed for Th2-associated chemokines (CCL17, CCL22, CCL11) and Th1-associated chemokine (CXCL10) using immunoassays.
- Statistical comparison of chemokine ratios (log-transformed) between supplementation groups and placebo, adjusting for covariates.
Main Results:
- Both EPA and DHA supplementation groups showed significantly lower Th2/Th1 chemokine ratios compared to placebo after adjusting for delivery mode, gestational age, and birthweight.
- Cesarean delivery was associated with significantly higher Th2/Th1 chemokine ratios compared to vaginal delivery.
- Specific chemokines analyzed included macrophage-derived chemokine (CCL22)/interferon-inducible protein-10 (CXCL10) and thymus and activation-regulated chemokine (CCL17)/interferon-inducible protein-10 (CXCL10).
Conclusions:
- Prenatal EPA and DHA supplementation effectively reduces fetal Th2/Th1 immune deviation, potentially lowering allergy risk.
- Cesarean delivery is associated with a more pronounced Th2-skewed immune profile at birth.
- Findings highlight the role of maternal nutrition and delivery method in shaping neonatal immune responses.
Objective:
Fetal dysregulation of T helper cell pathways may predispose to allergy, as high cord blood T helper 2/T helper 1 ratios have been shown to precede development of allergic diseases. We aimed to determine whether prenatal eicosapentaenoic acid and docosahexaenoic acid supplementation reduces T helper 2 to T helper 1-associated chemokine ratios. We also explored the effect of mode of delivery on T helper 2/T helper 1 ratios.
Study Design:
We conducted a secondary analysis of a randomized placebo controlled trial initially performed to assess the effects of docosahexaenoic acid or eicosapentaenoic acid supplementation on pregnancy-related depressive symptoms among 126 participants. Cord plasma specimens from 98 newborns were assayed for chemokines associated with T helper 2 (thymus and activation-regulated chemokine [CCL17], macrophage-derived chemokine [CCL22], eotaxin [CCL 11]) and T helper 1 (interferon-inducible protein-10 [CXCL 10]) by enzyme-linked immunosorbent assay and Multiplex immunoassays. Ratios of log-transformed chemokines macrophage-derived chemokine/interferon-inducible protein-10 and thymus and activation-regulated chemokine/interferon-inducible protein-10 were compared between groups by analyses of variance. Multiple linear regression was performed to examine associations between treatments and chemokine ratios, adjusting for covariates.
Results:
After adjusting for gestational age at delivery, birthweight, and mode of delivery, both omega-3 supplementation groups were associated with lower macrophage-derived chemokine/interferon-inducible protein-10 ratios than placebo (eicosapentaenoic acid: coefficient -1.8; 95% confidence interval [CI], -3.6 to -0.05; P = .04; docosahexaenoic acid: -2.0; 95% CI, -3.9 to -0.07; P = .04). Similar associations were found for thymus and activation-regulated chemokine/interferon-inducible protein-10 (eicosapentaenoic acid: -1.5; 95% CI, -3.0 to 0.06; P = .06; docosahexaenoic acid -2.2; 95% CI, -3.8 to -0.52; P = .01). Cesarean delivery was associated with higher macrophage-derived chemokine/interferon-inducible protein-10 (1.6; 95% CI, 0.01-3.3; P = .049) and thymus and activation-regulated chemokine/interferon-inducible protein-10 (1.5; 95% CI, 0.1-2.9; P = .042) ratios than vaginal delivery.
Conclusion:
Prenatal supplementation with eicosapentaenoic acid and docosahexaenoic acid resulted in decreased cord blood T helper 2/T helper 1 chemokine ratios. Cesarean delivery was associated with a pronounced T helper 2 deviation at birth.
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