Omega-3s, infants, and kids: New evidence for healthy mental and physical development

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Omega-3 fatty acids are critical nutrients for the developing fetus and the growing child. Published studies attest to the benefits of increasing omega-3 intake levels through dietary practices as well as dietary supplements, especially in pregnant women and in early childhood development. Why? Omega-3 long-chain polyunsaturated fats (PUFA) play major roles in embryonic development that span the gamut of human physiology.

Docosahexaenoic acid (DHA), in particular, is one of the most critical omega-3 fatty acids for fetal development. This is illustrated by the fact that, while concentrations of all fatty acids in maternal blood increase during pregnancy, the concentration of DHA specifically decreases, indicating the growing fetus’s need for DHA. In addition, DHA is one of the few fatty acids that is preferentially transferred to the placenta through the mother’s cord blood.¹

DHA and other omega-3 fatty acids, including eicosapentaenoic acid (EPA), remain of critical importance after birth, in early childhood and through adolescence. Unfortunately, the majority of DHA and EPA intake comes from the diet, and it has been shown that dietary intake of these essential omega-3s by both young and old remains woefully inadequate. According to National Institutes of Health data, children and teens average about a 40-mg total daily DHA + EPA intake from dietary sources, while adults average about 90 mg.² This is substantially lower than the 500 mg/day that the Global Organization for EPA and DHA Omega-3 (GOED; Salt Lake City) recommends for health maintenance,³ and does little to fulfill potential daily requirements for these key nutritional factors.

This is concerning, given that ongoing research continues to point to the great need for omega-3 fatty acids for healthy development. Ahead, we highlight some recent studies in the areas of fetal development, childhood growth, and brain development.

Preterm Birth and Fetal Growth

Omega-3 fatty acids, in particular DHA, support several aspects of fetal growth. Several, but not all, recent studies indicate that higher intake of omega-3 fatty acids during pregnancy may reduce the incidence of preterm birth and help reduce the likelihood of children being born with low or very low birth weight. Additional research points to the benefits of DHA intake for addressing other areas of fetal development.

A recently conducted analysis led by Susan Carlson from the University of Kansas Medical Center (Kansas City) took data from two clinical studies conducted earlier which assessed other pregnancy-related outcomes in women supplementing with DHA. The University of Kansas researchers performed a secondary analysis on this data looking specifically at the relationship between DHA supplement dosage and the incidence of preterm birth and birth weight in 345 pregnant women.⁴ In the original studies, healthy pregnant women with singleton pregnancies (no twins, etc.) were assigned to supplement with 600 mg/day of DHA or a corn-and-soybean-oil placebo beginning between week 12 and 20 of gestation until delivery.

Because supplementation compliance was pointed out as an issue of concern in the original studies, the authors looked at the relationship between compliance and the relevant endpoints of preterm delivery and birth weight. They found that the incidence of low and very low birth weight, as well as preterm deliveries, decreased significantly with increased compliance (and therefore greater DHA intake). Upon assessing the data, they determined that a rate of about 50% compliance (or an average intake of 285 mg of DHA/day) reduced preterm birth and reduced low- and very-low-birth-weight rates by nearly half. Increasing the dose of DHA even further (up to 600 mg/day) led to additional declines in preterm birth as well as very-low-birth-weight deliveries.

In another investigation, Annie Penfield-Cyr from Brigham and Women’s Hospital (Boston) led a secondary analysis of data from the Maternal-Fetal Medicine Units Network randomized controlled trial assessing whether supplementation with 2 g of omega-3 fatty acids daily (as 800 mg DHA and 1200 mg EPA) during pregnancy (beginning between weeks 16 and 22) prevented recurrent preterm birth.⁵

While the primary study did not show a benefit of omega-3 supplementation in preventing preterm birth⁶, this secondary analysis looked at whether the ratio of pro-inflammatory-to-inflammatory fatty acids (omega-6:omega-3 ratio) measured between week 25 and 28 of pregnancy impacted fetal growth parameters. Furthermore, the participants were divided into two subgroups based on their body mass index (BMI) and classified as lean (18.5-24.9 kg/m²) or overweight/obese (>25 kg/m²). The analysis included 440 pregnant women with a prior history of preterm delivery.

Of the women taking omega-3 supplements during their pregnancy, the researchers found that those classified as obese/overweight with higher omega-6:omega-3 ratios showed impaired fetal growth and shorter gestational length. The babies of these mothers also had a higher incidence of respiratory distress after birth as well as increased hospital stays. These results indicate that higher maternal inflammation (as measured by omega-6:omega-3 ratios during pregnancy) may be a marker of adverse fetal growth outcomes, especially in overweight and obese pregnant women. Because supplementation with omega-3 fatty acids can modify maternal inflammation, it may have a protective effect on fetal growth parameters.

A more recent, large, double-blind, multi-center study performed in Australia and led by Maria Makrides from the South Australian Health and Medical Research Institute (North Terrace, Adelaide, Australia) followed 5,544 pregnancies in which women were asked to supplement with 900 mg of omega-3 fatty acids or placebo daily beginning before 20 weeks of gestation to the end of pregnancy.⁷ The primary outcome of this study was early preterm delivery.

The results showed that early preterm delivery occurred in 2.0% of the women taking the placebo, while it occurred in 2.2% of those taking omega-3 fatty acids; however, the differences were not statistically significant. On the other hand, a significantly higher percentage of infants born to women taking the omega-3 supplements were very large for gestational age at the time of birth. Given these results, the impact of omega-3 supplementation on preterm birth remains unclear and requires further analysis.

Questions regarding the optimal dose of omega-3s during pregnancy as well as which populations benefit the most remain to be answered. Additionally, the authors of this study mention that previous studies have found that women with the lowest baseline levels of omega-3s are likely to receive the most benefit from supplementation; in the current study, that analysis was not performed, but could very well have resulted in similar findings. It is likely that women with certain baseline risk factors would benefit significantly more than others from omega-3 intake during pregnancy.

Childhood Growth and Healthy Body Composition

Omega-3 intake at a young age and during development has been found to confer significant benefits on several aspects of childhood growth. Research has shown that omega-3s, whether consumed by the mother in pregnancy or by the child during his or her early years, are likely to positively influence body composition and overall growth.

In a recent trial led by Rebecca Vinding from the University of Copenhagen (Copenhagen, Denmark), researchers studying fish oil supplementation during pregnancy and its effects on childhood growth found significant benefits for bone health as well as lean and fat mass.⁸

In the double-blind, placebo-controlled study, researchers followed 736 women and their offspring until age six. The women were asked to supplement with fish oil (2.4 g/day containing 55% EPA and 37% DHA) or an olive oil placebo, from week 24 of pregnancy until one week after birth.

The results indicated that fish oil during pregnancy may have a general and beneficial growth-stimulating effect on the offspring. Significant increases were seen in BMI, weight-to-height ratio, and waist circumference in the offspring between ages 0 and 6 in the fish oil group, but not in the olive oil group; however, it should be noted that these increases did not lead to an increased risk of obesity. Dual-energy x-ray absorptiometry scans (DXA) showed a significantly higher increase in lean mass in the fish oil group versus olive oil, and a higher bone mineral content, revealing that maternal fish oil supplementation led to a proportional increase in lean mass, bone mass, and fat mass.

An additional study explored the impact of maternal DHA supplementation on child body composition at five years of age. Led by Brandon Hidaka from the University of Kansas Medical Center (Kansas City), researchers measured body composition of 154 five-year-old children whose mothers had supplemented with 600 mg of DHA or a placebo during pregnancy.⁹ The mothers started out with poor DHA status at the beginning of the study and commenced supplementation from before 20 weeks of gestation to birth.¹⁰

For the present analysis, researchers used air-displacement plethysmography to assess body composition in the children.⁹ These measurements were compared to three different indicators of DHA status in the mothers. The results of the study showed that maternal red blood cell phospholipid DHA status at delivery was significantly correlated with higher fat-free mass in the children at age five, while the other two measures of DHA status (which included change in maternal blood DHA levels and being a part of the intent-to-treat DHA group) showed a favorable trend for this effect but did not reach statistical significance. The takeaway: overall higher DHA status in mothers during pregnancy had a favorable impact on lean mass in their children at five years of age.

Brain Development

PUFA, and particularly DHA, are known to be important building blocks for brain development. Several studies suggest that supplementation of omega-3 fatty acids either by the mother during pregnancy or by children in their early years may have lasting benefits for brain function and cognition.

Rebecca Lepping and colleagues from University of Kansas Medical Center (Kansas City) conducted a study to evaluate the effect of consuming long-chain-PUFA–fortified infant formula (containing arachidonic acid/ARA and DHA) during the first year of life on brain development at age nine.¹¹

In the study, a total of 42 children who consumed formula without long-chain PUFA, or with 0.64% ARA plus three different concentrations of DHA (0.32%, 0.64%, or 0.96%), were then evaluated using various magnetic resonance imaging (MRI) techniques to assess effects on brain structure, function, and metabolism. Following functional MRI analysis, researchers found that children who had consumed long-chain-PUFA–fortified formula during the first year of life had greater brain activation in the anterior cingulate cortex and parietal regions when undergoing the Flanker task (a measure of the brain’s ability to inhibit responses that are inappropriate in a given context), indicating greater inhibition.

Furthermore, resting-state MRI analysis of each of the groups found that those consuming the formula fortified with 0.64% DHA showed greater connectivity between the prefrontal and parietal regions of the brain compared to all other groups. In addition, brain white matter volume in the prefrontal and anterior cingulate cortex increased in the 0.32%- and 0.64%-DHA groups. These results suggest that fortification of formula-fed infants with DHA during their first year of life can have significant lasting benefits for neurological development, including brain structure and function.

Another study looked at the effect on infant brain volumes of a DHA-enriched supplement given to mothers during pregnancy. Led by Enitan Ogundipe from Imperial College of London (London), researchers recruited 300 pregnant women and asked them to consume two capsules of the DHA-based supplement (containing 300 mg DHA, 42 mg EPA, and 8.4 mg ARA per capsule) or a placebo until delivery.¹²

At the end of the study, 86 infants underwent brain MRI scans at an average gestational age of 43 weeks. In female infants, no significant differences in brain volume were noted in the supplement group versus placebo; however, in male infants in the supplement group, DHA led to increased birth length and head circumference as well as increased total brain, cortex, corpus callosum, and whole gray matter volume compared to placebo. The study findings indicate a gender-specific effect of DHA and highlights the need for ensuring optimal DHA status in pregnant women for supporting healthy infant brain development.

Crucial for Kids

The research on omega-3 fats and their ability to positively impact the developing fetus and growing children is clear. Nutritional interventions incorporating these essential and healthy fats can yield significant benefits for childhood growth and development.

Although researchers must continue to tease out issues around dosing as well as identifying population groups that are likely to benefit the most, adding DHA and other omega-3 fatty acids to a child or expecting mother’s daily routine may be a prudent step in ensuring individuals are meeting their need for these critical nutritional factors.

References:

1. Demmelmair H et al. “Importance of fatty acids in the perinatal period.” World Review of Nutrition and Dietetics. Published online November 24, 2014.
2. National Institutes of Health. Omega-3 Fatty Acids: Fact Sheet for Health Professionals. Updated July 9, 2019. Accessed at: https://ods.od.nih.gov/factsheets/Omega3FattyAcids-HealthProfessional
3. Global Organization for EPA and DHA Omega-3 Intake Recommendations. Accessed at: https://goedomega3.com/intake-recommendations
4. Carlson SE et al. “Dose-response relationship between docosahexaenoic acid (DHA) intake and lower rates of early preterm birth, low birth weight and very low birth weight.” Prostaglandins, Leukotrienes, and Essential Fatty Acids. Published online September 20, 2018.
5. Penfield-Cyr A et al. “Maternal BMI, mid-pregnancy fatty acid concentrations, and perinatal outcomes.” Clinical Therapeutics. Published online September 19, 2018.
6. Harper M et al. “Omega-3 fatty acid supplementation to prevent recurrent preterm birth: a randomized controlled trial.” Obstetrics and Gynecology, vol. 11 (2 Pt 1): 234-242
7. Makrides M et al. “A randomized trial of prenatal n-3 fatty acid supplementation and preterm delivery.” New England Journal of Medicine, vol. 381, no. 11 (September 12, 2019): 1035-1045
8. Vinding RK et al. “Effect of fish oil supplementation in pregnancy on bone, lean, and fat mass at six years: randomised clinical trial.” BMJ. Published online September 4, 2018.
9. Hidaka BH et al. “Intrauterine DHA exposure and child body composition at 5 y: exploratory analysis of a randomized controlled trial of prenatal DHA supplementation.” American Journal of Clinical Nutrition, vol. 107, no. 1 (January 1, 2018): 35-42
10. Carlson SE et al. “DHA supplementation and pregnancy outcomes.” American Journal of Clinical Nutrition, vol. 97, no. 4 (April 2013): 808-815
11. Lepping RJ et al. “Long-chain polyunsaturated fatty acid supplementation in the first year of life affects brain function, structure, and metabolism at age nine years.” Developmental Psychobiology. Published online October 11, 2018.
12. Ogundipe E et al. “Randomized controlled trial of brain specific fatty acid supplementation in pregnant women increases brain volumes on MRI scans of their newborn infants.” Prostaglandins, Leukotrienes, and Essential Fatty Acids. Published online September 21, 2018.