**Conflict of interest**

*Maternal and Child Health Matters Around the World*

omega-3 LCPUFAs can affect inflammatory cytokines [137].

but much remains to be investigated in these fields.

DHA supplementation during the third trimester of pregnancy and during breastfeeding can affect cytokine production, increasing anti-inflammatory

cytokine levels and decreasing pro-inflammatory cytokine levels. These effects may translate to a lower risk of pregnancy-related complications and childhood disease,

We thank all the members of our team who have participated in this work: Julio Ochoa, Federico Lara Villoslada, Naroa Kajarabille, Pedro Saavedra-Santana, Jose

CT group. Additionally, TNF-α was higher in CT children [26]. In a study on depression in pregnant women, it was also observed that prenatal EPA supplementation in particular reduced maternal levels of IL-6, Il-15, and TNF-α [131]. Clinically, these findings could translate to an increased anti-inflammatory "environment" provided by omega-3 LCPUFAs. TNF-α and IL-6 are pro-inflammatory, and IL-10, although it has both effects [131, 132], is considered the principal regulator of T cells and may act as an anti-inflammatory mediator of omega-3 LCPUFAs [133]. However, some studies have found no correlation between DHA and different cytokines: a study by Hawkes et al. [129] found that women receiving supplementation during pregnancy with a combination of 600 mg DHA plus 140 mg EPA daily for 4 weeks had an increase in omega-3 LCPUFA levels in the cells studied. DHA levels increased in a dose-dependent manner in the plasma and breast milk, which highlights the benefits of this dietary intervention. However, no significant differences were found between groups in the production of cytokines, either in breast milk cells or in peripheral blood. In addition to the dose, the duration of supplementation could be the key. There has been some investigation into the clinical effect that supplementation may have on infants [133–136]. It has been observed that increased dietary intake of salmon during pregnancy increases levels of omega-3 LCPUFAs in umbilical cord plasma and affects cytokine production in neonates, with lower levels of IL-2, IL-4, IL-5, IL-10, and TNF-α in response to various stimuli [133]. Reduced IL-10 production has also been observed in vitro following stimulation with cat allergens in an atopic population [134]. Increased DHA and EPA in mother and child results in lower levels of PGE-2, a pro-inflammatory eicosanoid and inducer of IL-10 production, which could explain the reduced secretion of IL-10 in these individuals. This concept is also supported by Warstedt et al. [136] who suggested that reduced maternal levels of PGE-2 after omega-3 LCPUFA supplementation could contribute to a foetal immune system less prone to developing inflammatory disease such as allergies, since eicosanoids, cytokines, and chemokines are closely associated with the immune response. However, although results have been promising, it is still unclear whether or not omega-3 LCPUFAs affect the development of atopy [4]. Changes in fatty acid levels have been demonstrated to affect cytokine levels. A positive association has been observed between DHA and IL-10 such that at higher concentrations of DHA, IL-10 secretion is increased [26, 131]. Likewise, DHA has been negatively associated with IL-6, which could translate to an increased antiinflammatory effect [26, 137]. These findings will need to be confirmed in future studies to clarify the uncertainties regarding the various mechanisms by which

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**7. Conclusions**

**Acknowledgements**

The authors declare no conflict of interest.
