Nutrition in pregnancy, during lactation, childhood, and later stages has a fundamental influence on overall development. There is a growing research interest on the role of key dietary nutrients in fetal health. Omega-3 polyunsaturated fatty acids (n-3 LCPUFAs) play an important role in brain development and function. Evidence from animal models of dietary n-3 LCPUFAs deficiency suggests that these fatty acids promote early brain development and regulate behavioral and neurochemical aspects related to mood disorders (stress responses, depression, and aggression and growth, memory, and cognitive functions). Preclinical and clinical studies suggest the role of n-3 LCPUFAs on neurodevelopment and growth. n-3 LCPUFAs may be an effective adjunctive factor for neural development, growth, and cognitive development, but further large-scale, well-controlled trials and preclinical studies are needed to examine its clinical mechanisms and possible benefits. The present paper discusses the use of n-3 LCPUFAs during different developmental stages and the investigation of different sources of consumption. The paper summarizes the role of n-3 LCPUFAs levels during critical periods and their effects on the children’s neurodevelopment, nutrition, and growth.
Arachidonic acid (AA; 20:4n-6) and Docosahexaenoic acid (DHA; 22:5n-3) are essential for brain growth and cognitive development; they also accumulate rapidly in the brain and retina during the later stages of gestation and early postnatal life [
During pregnancy, AA and DHA are transported across the placenta into fetal venous blood [
After birth, breast milk is the source of AA and DHA to the neonate; the content of essential polyunsaturated fatty acids (PUFAs) in breast milk is dependent on the maternal intake of these fatty acids [
The contribution of DHA for better neurodevelopment has been documented in breastfed infants. However, the effects of different levels of DHA in human milk and maternal DHA supplementation limited to the lactation period are still under investigation [
Researchers and mothers have turned to fish oil supplements, which are generally low in contaminants (methylmercury) and can provide substantially higher doses of n-3 LCPUFAs than most adults are able to consume in their diets [
It is evident that several worldwide health agencies recognize the importance of increasing dietary intake of n-3 LCPUFAs. The daily DHA recommendation during pregnancy from the Expert Committee ranges from 200–300 mg/daily (modified from [
In the present paper, we review the scientific evidence that relates n-3 LCPUFAs levels during these critical periods to children’s neurodevelopment, nutrition, and growth. PubMed database was used to identify relevant studies, and reference lists from retrieved studies were reviewed. Study selections were limited to English and Portuguese studies involving humans and experimental studies, from 1980 to 2012.
In Iran, authors found a significant difference in the total n-3 LCPUFAs and DHA in breast milk in women in coastal cities compared with those in inland cities. Coastal mothers showed a significantly higher intake of fish or seafood compared with inland mothers
A randomized controlled trial investigated direct supplementation of high dose fish oil to term infants in the early postnatal period (with regard to feeding practices). Infants were supplemented daily, from birth to six months, with fish oil supplement or placebo. The results indicate that direct fish oil supplementation can significantly elevate DHA levels in infancy. The study showed a successful strategy for raising infant DHA status [
Long-chain polyunsaturated fatty acids (LCPUFAs) play an important role in the central nervous system (CNS) and are essential for early brain development. LCPUFAs comprise approximately 15 to 30% of the brain’s dry weight [
The fastest stage of neural development is during fetal growth. However, there is also significant development during the first five years of postnatal life. At this time, environmental factors, including nutrient intake, play a critical role in the development of the brain’s cytoarchitecture [
During the third trimester of pregnancy, fetuses require approximately 40 to 60 mg of n-3 LCPUFAs per kilogram of body weight per day [
Studies have shown evidence for the neurodevelopmental benefits of dietary PUFA during pregnancy and infancy [
Several studies have shown the cognitive benefits of high levels of consumption of n-3 LCPUFA in elderly populations [
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Maternal intake of n-3 LCPUFA and breastfeeding predicted oppositional defiant and conduct disorder and comorbid externalizing disorder, before adjustment for confounding factors. However, there was no association between intake of n-3 LCPUFA by the mother or child with any type of externalizing disorder once sociodemographic factors were taken into account [
Confounding factors associated with inherited factors such as maternal IQ [
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A review of studies that investigated the effects of n-3 LCPUFAs and mental illness found consistent evidence about the beneficial effects of n-3 LCPUFAs in relation to mood disorders. The results of studies that investigated an association between n-3 LCPUFAs and schizophrenia, borderline personality, attention deficit hyperactivity, and symptoms of anxiety are inconclusive. The results do not support indication of monotherapy or adjunctive treatment for mental illnesses [
However, there is evidence of n-3 LCPUFAs deficiency identified in women who develop postpartum depression. Postpartum depression is a serious mood disorder with the same symptoms as major depressive disorders (depressed mood, loss of interest in pleasurable activities, changes in sleep patterns and weight, and reduced cognitive abilities and concentration) [
Observational studies show that prevalence of postpartum depression may be associated with n-3 LCPUFAs (FAs) intake and status. However, there are few controlled trials that have evaluated the effects of increasing the intakes of FAs on depression symptoms in postpartum women. Most interventions studies investigated a reduced number of patients and typically provided fish oil-based supplements that contained high doses of EPA and DHA [
A recent review showed unclear effects of maternal prenatal and postnatal LC-PUFAs supplementation on global neurobehavioral outcomes for children born to term. However, n-3 LCPUFAs supplementation for breastfeeding women of preterm infants improved performance on tests of global neurodevelopment [
Fish oil supplementation (4 g of fish oil with 1.1 g EPA and 2.2 DHA/daily) starting at 20 weeks of pregnancy until birth significantly increased the fatty acid composition of maternal and neonatal erythrocytes in comparison with olive oil supplementation. The effects were partially sustained until at least 6 weeks postpartum. Similarly, administration of n-6 polyunsaturated fatty acids AA was associated with significantly lower erythrocytes in neonates in the fish oil group in comparison with controls [
A DOMInO (DHA to Optimize Mother Infant Outcome) study with 2,399 women investigated whether DHA supplementation during the second half of gestation reduced the risk for depressed maternal mood (Edinburgh Postnatal Depression Scale) during the postpartum period. Women in the DHA group consumed 3 daily capsules of fish oil that contained a total of 800 mg DHA and 100 mg EPA (eicosapentaenoic acid); women in the control group consumed similar supplement levels of vegetable oil. The group given DHA did not show significant reduction in the rates of PND [
In the same study, researchers investigated early cognitive development in the offspring at 18 months of age. The results did not show an overall effect of DHA on development (assessed using the Bayley Scales of Infant and Toddler Development including cognitive scores and language scores [
Daily maternal supplementation with 1.6 g EPA or 1.1 g DHA from the 25th gestational week to an average 3-4 months in early breastfeeding decreased the risk for food allergies and IgE-associated eczema during the first year of life. The effects were shown in infants with a family history of allergic disease compared with a placebo group [
Supplementation with a relatively high dose of fish oil (1.1 g EPA and 2.2 g DHA/daily) during the last 20 weeks of pregnancy is not only safe but also has potential beneficial effects, but the effects need to be further investigated. At age 2.5 years, children in the fish oil-supplemented group showed a significantly higher score for hand-eye coordination than children in the placebo group. There was a correlation between hand-eye coordination scores with n-3 LCPUFAs levels in cord blood erythrocytes, and a negative correlation with n-6 PUFA [
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A multicenter, randomized controlled trial from DINO (Docosahexaenoic Acid for the Improvement of Neurodevelopmental Outcome in Preterm Infants) with 657 lactating administered six 500 mg DHA-rich tuna oil capsules per day (for breast milk DHA concentration). The study showed that a DHA dose of approximately 1% total fatty acids in early life did not increase Bayley Mental Developmental (MDI) scores of preterm infants with less than 33 weeks of gestation. However, the dosage improved the MDI scores of girls [
In another study, breast-feeding women received identical capsules containing either DHA algal oil (200 mg/d of DHA) or a vegetable oil (no DHA) from delivery until 4 months postpartum. The results showed that at 5 years, there were no differences in visual function (Bailey-Lovie acuity chart), transient visual evoked potential, or sweep visual evoked potential testing between children whose mothers received DHA versus placebo. However, children whose mothers received DHA versus placebo performed significantly better on the Sustained Attention Subscale of the Leiter International Performance Scale. There were no statistically significant differences between groups on other neuropsychological domains [
Yet another study was carried out with the objective of determining the effect of DHA supplementation on neurodevelopment status and visual function. Breastfeeding mothers were administered capsules containing either high-DHA concentration algal oil (200 mg DHA/day) or a vegetable oil (no DHA) to breastfeeding women for 4 months after delivery. The intervention group showed 50% greater content of maternal plasma phospholipids DHA, 75% greater content of DHA in milk lipids, and 35% greater content of DHA in infant plasma phospholipids. However, higher infant plasma phospholipids DHA content did not show effects on visual acuity at either 4 or 8 months of age [
The DINO Trial DHA found that supplementation for infants <33 weeks gestation with tuna oil capsules reduced the incidence of bronchopulmonary dysplasia in boys and in all infants with a birth weight <1250 g; it also reduced the incidence of reported hay fever in boys at either 12 or 18 months [
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In an observational study of subjects born in 1936 whose mental ability was tested in 1947 and who were followed up in 2000-2001, the childhood IQ did not differ significantly by category of food supplement use. However, at the age of 64 years, cognitive function was higher in food supplement users than in nonusers, before adjustment for childhood IQ [
A recent review limited to human studies published in English from 2000 until 2010 on n-3 and growth suggests that n-3 (DHA in particular) during pregnancy, lactation and early life may be associated with significant benefits for infant growth and development in developing countries. Studies in developing countries show that a higher n-3 intake or supplementation during pregnancy may result in improvements in birth weight, length, and gestational age. Limited data from developing countries suggest that ALA or DHA supplementation during lactation and in infants may be beneficial for growth and development of young children; these benefits are more pronounced in undernourished children. However, there is no evidence of improvements in growth following n-3 supplementation in children >2 years of age [
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An interventional study carried out in Brazil showed that postnatal sardine consumption (100 g of sardines two or three times a week) contributed to an increase omega-3 series fatty acids (DHA and DPA) on the composition of breast milk of mothers at 15 and 30 days into the study [
In a prospective, observational cohort study with 2109 subjects who were enrolled in the Project Viva, in the USA, the authors investigated if maternal marine n-3 LCPUFAs and seafood intake were associated with birth weight, birthweight for gestational-age
A prospective study with 62099 women in Norway (Norwegian Mother and Child Cohort Study-MoBa) investigated the influence of maternal intakes of seafood and supplementary n-3 LCPUFAs in infant birth weight, length, and head circumference. The researchers found that maternal seafood consumption was positively associated with birth size, driven by lean fish intake, while supplementary n-3 intake was negatively associated with infant head circumference [
A study was conducted with 22 Lister Hooded rats that are divided into two groups: the control group (CG) which received a casein-based diet, and the flaxseed group (FG) which received 25% flaxseed diet supplement, and 14% casein showed that, during gestation and lactation, the FG was similar to the CG group in relation to food intake and litter size. The same result was observed for milk fat content and total energy value. At weaning, the FG group was similar to the CG group in both in offspring body weight and in weight gain of pups during lactation [
A study with female Wistar rats
A recent review shows that LC-PUFAs supplementation during pregnancy is associated with modest increases in birth size in both low-income and high-income populations. However, postnatal supplementation with LC-PUFAs did not influence infant growth [
Babies born of primiparous Mexican women who received 400 mg/d of algal DHA during the second half of the pregnancy term were heavier and had larger head circumferences at birth than children whose mothers received placebo (olive oil). However, no effect was observed in multiparous mothers. Children of primiparous women who were given DHA were taller at 18 months than those of primiparous women given placebo. The authors suggest that since primiparous women were, on average, younger than the multiparous women, their own body stores of DHA are not well established and available to the fetus and infant [
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Supplementation with fish oil (1.1 g EPA and 2.2 DHA/daily) or olive oil starting at 18–20 weeks of pregnancy and continued until delivery showed similar growth measurements in the two groups at age
A randomized, double-blind trial gave lactating mothers fish oil or olive oil supplements for 4 months; the study followed infant development for 2.5 years and showed that children from the fish oil group had larger head circumference and higher BMI than those in the olive oil group after adjustment for relevant confounds. Both body composition and head circumference at 2.5 years of age positively correlated with the DHA content of maternal red blood cells at the end of the intervention [
Experimental, biochemical, and epidemiological evidence support the hypothesis that low n-3 polyunsaturated fatty acids (n-3 LCPUFA) levels are associated with dysfunctional brain development and impaired growth; the evidence also shows that n-3 supplementation is useful for improvement of specific parameters, especially those related to memory and cognition. However, the precise definition of the method of use and dosages is still unclear. Large-scale, well-controlled trials should be carried out to confirm the efficacy of the acids and establish the minimum dose and length of supplementation to significantly improve clinical outcomes. It is also important to determine the use of the acids on different stages of development. n-3 LCPUFAs represent an attractive supplementary alternative, because they are perceived as a natural substance rather than an artificial supplement. In sum, the dietary consumption and supplementation of n-3 LCPUFAs could provide physical and mental health benefits for development.
The authors would like to acknowledge the contribution of Carla Dalmaz (Biochemistry Department, UFRGS, Brazil) in the discussion and preparation of the early draft of this paper. There is no conflict of interests, either financial or of any other nature in relation to the present work. Financial support was received from ARD/FAPERGS 2010 (Silveira PP, 10/0474-2); Universal National Counsel of Technological and Scientific Development (CNPq)—Brazil 2010 (Silveira PP, 478820/2010-0); FIPE/HCPA (GPPG 09-410); Foundation for the Coordination of Higher Education and Graduate Training (CAPES); INCT Translational Medicine (CNPq) 573671/2008-7.