Role of Omega-3 Fatty Acids in Maternal, Fetal, Infant and Child Wellbeing

Ellen Mozurkewich; Deborah R Berman; Julie Chilimigras


Expert Rev of Obstet Gynecol. 2010;5(1):125-138. 

In This Article

Fetal Brain Development & Early Childhood IQ

Evidence from Epidemiologic Studies

The human brain is predominantly composed of lipids, with phospholipids making up 22% of the cerebral cortex and 24% of the white matter.[75] In the third trimester of pregnancy, omega-3 fatty acids are selectively transferred to the fetus to meet the demands of rapid brain growth, and DHA accumulates in the fetal brain at a rate of 14.5 mg/week.[76] DHA is the predominant fatty acid found in the brain, although the proportion of DHA varies according to brain region.[76] It is most prevalent in growth cones, synaptic membranes, astrocytes, myelin and microsomal and mitochrondrial membranes.[76,77] DHA has been shown to support neuronal proliferation and decrease neuron apoptosis.[77] Brains of infants born before 33 weeks' gestation are relatively deficient in DHA compared with brains of infants born at term, and survivors of prematurity exhibit permanently reduced gray and white matter volumes,[78] a finding that may explain some of the subtle developmental abnormalities observed in survivors of prematurity.[76] Owing to the importance of DHA in brain structure, it has been hypothesized that the relative imbalance of omega-6 and omega-3 fatty acids in the modern diet may have adverse developmental consequences, such that current dietary habits in the industrialized world may not optimally meet the needs of the developing brain.[77]

In a recently published British cohort study, Hibbeln stratified prenatal seafood consumption as greater than or less than 340 g/week (two fish meals). Children born to studied pregnancies were followed-up to 8 years of age, and verbal IQ and other developmental outcomes were measured. After adjustment for socioeconomic status and other potentially confounding variables, children born to mothers who consumed less than 340 g of seafood per week were at increased risk for low verbal IQ, prosocial behavior, fine motor, communication and social development scores.[79] The authors advised re-examination of dietary guidelines advising limiting fish consumption in pregnancy to two or fewer fish meals per week.

Evidence from Clinical Trials

Developmental outcomes have been assessed in several interventional trials of LC-PUFA supplementation of mothers in pregnancy and lactation, as well as supplementation of formula-fed term and preterm neonates. In a double-blind, randomized, controlled trial of very long-chain PUFA supplementation among 341 Norwegian women attending two antenatal clinics, cod liver oil supplementation was compared with corn oil supplementation. Of the 135 women out of this total who were invited to bring their infants for cognitive testing at 4 years of age, 90 completed this process. Children from the cod liver oil group were found to have significantly higher Mental Processing Composite subtest scores at 4 years of age than children born in the corn oil group. There was a trend to higher scores on other subtests in the cod liver oil group, but this trend did not reach statistical significance.[80] Likewise, in a follow-up study of infants born in a randomized, controlled trial of DHA dietary supplementation of economically disadvantaged women through DHA-fortified eggs, Colombo et al. demonstrated that higher maternal erythrocyte DHA concentrations at delivery were associated with improved measures of infant attention in tests administered in the first 2 years of life.[81] By contrast, in a randomized, controlled trial of fish oil supplementation versus olive oil placebo in 122 lactating mothers with habitual fish intake below the population median of Denmark, no beneficial effects of supplementation were demonstrated with regard to problem-solving ability at 9 months and language development at 1 and 2 years of age.[82]

In an attempt to improve visual acuity and developmental outcomes, some manufacturers have added LC-PUFA (usually DHA and arachidonic acid) to infant formula. Two Cochrane systematic reviews of LC-PUFA supplementation of infant formula on infant development and cognition have been carried out among term and preterm infants.[83,84] The control formulas in most of these studies were supplemented with α-linolenic acid and linoleic acid, the precursor fatty acids to DHA and EPA and arachidonic acid, respectively. For supplementation of infants born at term, the reviewers combined 14 studies with 1719 subjects.[83] The nine studies that used visual acuity or visual evoked potential as the primary outcomes yielded inconsistent results, with three studies showing benefit and six studies showing no effect. Meta-analysis of the 11 studies that measured mental or psychomotor development index showed no difference in outcomes between supplemented and unsupplemented children. Likewise, in a systematic review of α-linolenic acid and linoleic acid supplementation of formula for preterm infants, Simmer et al. found no consistent beneficial or harmful effect of supplementation on visual acuity, neurodevelopment or growth.[84]

Subsequent to the search date of the two systematic reviews, Makrides et al. reported on the results of a randomized, controlled trial of high-dose DHA supplementation of 657 infants born before 33 weeks' gestation.[85] In this study, infants received either standard- or high-dose DHA through enteral feedings of breast milk or formula. Lactating mothers of randomized infants received either tuna oil capsules or soy oil placebo in order to create either DHA-enriched or standard composition milk. Infants of mothers who were not lactating received standard or high-DHA formula. Although the investigators found high-dose supplementation had no effect on the mental development index for the total group, DHA supplementation significantly improved mental development index among girls (adjusted mean difference 4.5; 95% CI: 0.5–8.5). Fewer infants who received the high-DHA diet had significantly delayed mental development.[85]


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