Maternal Docosahexaenoic Acid Supplementation Decreases Lung Inflammation in Hyperoxia-Exposed Newborn Mice

Abstract

DHA is a long-chain fatty acid that has potent antiinflammatory properties. Whereas maternal DHA dietary supplementation has been shown to improve cognitive development in infants fed DHA-supplemented milk, the antiinflammatory effects of maternal DHA supplementation on the developing fetus and neonate have not been extensively explored. Pregnant C3H/HeN dams were fed purified control or DHA-supplemented diets (~0.25% of total fat) at embryonic d 16 and consumed these diets throughout the study. At birth, the nursing mouse pups were placed in room air (RA; 21% O(2)) or >95% O(2) (hyperoxia) for up to 7 d. These studies tested the hypothesis that maternal DHA supplementation would decrease inflammation and improve alveolarization in the lungs of newborn mouse pups exposed to hyperoxia. Survival, inflammatory responses, and lung growth were compared among control diet/RA, DHA/RA, control/O(2), and DHA/O(2) pups. There were fewer neutrophils and macrophages in lung tissues from pups nursed by DHA-supplemented dams than in those nursed by dams fed the control diet at 7 d of hyperoxia exposure (P < 0.015). Although differences due to hyperoxia exposure were observed, maternal diet did not affect keratinocyte-derived chemokine, macrophage inflammatory protein-2, IL-1β, or TNFα mRNA levels in pup tissues. Hyperoxia also induced NF-κB activity, but maternal diet did not affect NF-κB or PPARγ activities. In mice, DHA supplementation decreases leukocyte infiltration in the offspring exposed to hyperoxia, suggesting a potential role for DHA supplementation as a therapy to reduce inflammation in preterm infants.

DHA suppresses chronic apoptosis in the lung caused by perinatal inflammation

“…that the combination of maternal inflammation and neonatal hyperoxia exposure causes an exacerbated pathophysiology with alterations in lung biology that persists into adulthood (24,(31)(32)(33). This critical phenotype is similar to that observed in a preterm infant that develops severe bronchopulmonary dysplasia (BPD) (9,28,29).…”

“…In earlier studies, we have documented improvements in lung growth and function in mice exposed to maternal inflammation and neonatal hyperoxia by supplementing the pregnant and nursing dams with docosahexaenoic acid (DHA) (24,31). In the present studies we tested the hypothesis that maternal DHA supplementation during the inflammatory period would prevent long-term dysregulation of cell death pathways.…”

“…437627; Calbiochem, Gibbstown, NJ) or an equal volume of saline, as previously reported (32,33,35). Also beginning on E16, dams injected with LPS or saline were placed on control diets (CD) or DHA-supplemented diets (DHA) until weaning, as described previously (22,31). At birth, each litter of newborn mice was paired with a litter born to a dam receiving the same embryonic exposures (LPS or saline, control or DHA diets), and the pups were pooled and redistributed randomly as previously described (33).…”

“…maternal inflammation; neonatal hyperoxia; docosahexaenoic acid, apoptosis THE LIFE-LONG EFFECTS of an adverse maternal environment on the developing fetus and the contributions of this perinatal milieu to adult disease pathogenesis are currently being defined (10,36). We have previously demonstrated in a mouse model that the combination of maternal inflammation and neonatal hyperoxia exposure causes an exacerbated pathophysiology with alterations in lung biology that persists into adulthood (24,(31)(32)(33). This critical phenotype is similar to that observed in a preterm infant that develops severe bronchopulmonary dysplasia (BPD) (9,28,29).…”

Omega-3 Long-Chain Polyunsaturated Fatty Acids for Extremely Preterm Infants: A Systematic Review

“…52 Maternal DHA supplementation reduces inflammation in the neonatal mouse hyperoxia model of BPD. 56 In extremely preterm infants, reduced serum DHA during the first postnatal month was associated with increased need for supplemental oxygen at 36 weeks PMA (odds ratio 2.5, 95% CI 1.3-5.0). 8 The ratio of n6-linoleic acid to n3-DHA in these infants was highly predictive of lung disease, confirming the importance of balanced ratios of LCPUFA and potential selective role of DHA in protecting against BPD.…”