What is DHA ?

What is DHA ?

Docosahexaenoic acid (DHA) is an essential fatty acid and a member of the omega-3 fatty acid family. Docosahexaenoic acid (DHA) is an “essential” fatty acid, meaning that people must obtain it from food or supplements because the human body cannot manufacture it ¹. Omega-3 fatty acids are important for a number of bodily functions, including muscle activity, blood clotting, digestion, fertility, and cell division and growth. Docosahexaenoic acid (DHA) is also found in all cell membranes, and play an important role as structural membrane lipids, particularly in nerve tissue for brain development and the retina of the eye ². Various organizations worldwide have made dietary recommendations for eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and fish intake that are primarily for coronary disease risk reduction and triglyceride lowering. Recommendations also have been made for docosahexaenoic acid (DHA) intake for pregnant women, infants, and vegetarians/vegans ³. Over the past decades, evidence has accumulated in support of the hypothesis that DHA (docosahexaenoic acid) may have an important role in pregnancy health and outcome, as well as in the postnatal development of perceptual and cognitive function in infancy.

What are Omega-3 fatty acids

Fats are essential for living organisms. Fatty acid molecules have a variable length carbon chain with a methyl terminus and a carboxylic acid head group ⁴. They can be categorized based on the degree of saturation of their carbon chains. Saturated fatty acids possess the maximal number of hydrogen atoms, while monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) have one, or two or more, double bonds, respectively.

Figure 1. Monounsaturated Fatty Acids Structure

Figure 2. Polyunsaturated Fatty Acids Structure

Figure 3. Omega-3 fatty acids and Omega-6 fatty acids structure

Figure 4. Conversion of dietary ALA to EPA and DHA via Desaturation, elongation and retroconversion of polyunsaturated fatty acids.

[Source ⁵]

Omega-3 fatty acids are long-chain polyunsaturated fatty acids (18–22 carbon atoms in chain length) with the first of many double bonds beginning with the third carbon atom, n-3, when counting from the methyl end of the fatty acid molecule (see Figure 3). The three principal omega-3 fatty acids are:

1. Alpha-linolenic acid (ALA) (18:3ω-3),
2. Eicosapentaenoic acid (EPA) (20:5ω-3),
3. Docosahexaenoic acid (DHA) (22:6ω-3).

The three principal omega-3 fatty acids are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). The main sources of alpha-linolenic acid (ALA) in the U.S. diet are vegetable oils, particularly canola and soybean oils; flaxseed oil is richer in ALA than soybean and canola oils but is not commonly consumed. ALA can be converted, usually in small amounts, into EPA and DHA in the body. EPA and DHA are found in seafood, including fatty fish (e.g., salmon, tuna, and trout) and shellfish (e.g., crab, mussels, and oysters).

Long-chain Omega-3 PUFAs are synthesized from the essential fatty acid linoleic acid (LA) and alpha-linolenic acid (ALA). An essential fatty acid cannot be made by the body and must be obtained through dietary sources. Fatty fish, such as mackerel, herring and salmon, provide an excellent source of the long-chain derivatives of ALA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ⁶. The typical North American diet provides about 1–3 g of n-3 PUFA alpha-linolenic acid (ALA) per day but only 0.10–0.15 g of EPA (Eicosapentaenoic acid) plus DHA (Docosahexaenoic acid) per day ⁷, ⁸. The results indicate that the majority of American are failing to meet intake recommendations for long chain Omega-3 PUFA and emphasize the need for strategies, to increase the availability and consumption of Omega-3-containing foods ².

Of the 20 or so edible fatty acids, only omega-3 and omega-6 fatty acids cannot be synthesized by the body ⁹. All of the omega-3 and omega-6 fatty acids accumulated by the fetus must ultimately be derived from the mother by placental transfer. The typical American diet is well-supplied with omega-6 fatty acids, particularly linoleic acid (LA), which is readily converted to arachidonic acid (AA). Omega-6 fatty acids can be found in the vegetable oils used in processed foods, fried foods, and condiments like salad dressings ¹⁰, ¹¹. One teaspoon of corn oil can satisfy the daily omega-6 requirement, but most individuals eat 10 to 20 times that amount ¹⁰, ¹¹.

Table 1. Adequate Intakes for Omega-3s

Age	Male	Female	Pregnancy	Lactation
Birth to 6 months*	0.5 g	0.5 g
7–12 months*	0.5 g	0.5 g
1–3 years**	0.7 g	0.7 g
4–8 years**	0.9 g	0.9 g
9–13 years**	1.2 g	1.0 g
14–18 years**	1.6 g	1.1 g	1.4 g	1.3 g
19-50 years**	1.6 g	1.1 g	1.4 g	1.3 g
51+ years**	1.6 g	1.1 g

*As total omega-3s
**As ALA

[Source: Institute of Medicine ¹²]

In contrast, the intake of omega-3 fatty acids is suboptimal ⁹. The richest dietary sources of omega-3 fatty acids are from marine sources, fish oil supplements, and selected vegetable oils like flaxseed (57% omega-3 fatty acids), canola (11% omega-3 fatty acids), and soybean (8% omega-3 fatty acids). Most individuals in the United States do not consume these omega-3-rich foods on a regular basis. The ratio of dietary omega- 6/omega-3 fatty acids in the American diet approximates 10 to 25:1 ¹¹.

The omega-3 fatty acid eicosapentaenoic acid (EPA) and the omega-6 fatty acid arachidonic acid (AA) are essential structural components of every cell in the body. Both eicosapentaenoic acid (EPA) and arachidonic acid (AA) serve as precursors for biologically active compounds called eicosanoids. These fatty acids compete for the enzyme systems cyclooxygenase, which makes prostaglandins and thromboxanes, and lipoxygenase, which makes leukotrienes. Diets that are rich in omega-6 fatty acids produce potent eicosanoids, whereas a diet with a more balanced intake of omega-6 and omega-3 fatty acids makes less inflammatory and less immunosuppressive eicosanoids ¹³.

Specific to pregnancy, although both DHA and arachidonic acid (AA) appear to be essential to fetal CNS development, the relatively poor intake of EPA coupled with the high intake of linoleic acid (which produces AA), may affect pregnancy outcome by altering the balance of the eicosanoids produced ¹⁴, ¹⁵. A high ratio of arachidonic acid (AA) to eicosapentaenoic acid (EPA) may promote untoward effects such as preterm labor and preeclampsia ¹⁶. A linoleic acid-rich diet produces an abundance of arachidonic acid (AA), which serves as a precursor of the potent 2-series prostaglandins (PGs) E2 and PGF2α, and the vasoconstrictor thromboxane (TX) A2. Both PGE2 and PGF2α are closely associated with the initiation of labor and preterm labor, whereas thromboxane A2 has been associated with preeclampsia ¹⁷, ¹⁸. Whereas the omega-3 fatty acid, DHA, is not usually considered to be involved with eicosanoid formation, EPA is a precursor for the 3-series of PGs and produces PGE3 and PGI3, which promote relaxation of myometrium ¹⁹, ²⁰. Also, EPA and DHA competitively displace arachidonic acid (AA) in the membrane phospholipids and thereby reduce production of 2-series eicosanoids ²¹. Thus, a diet that provides a closer balance of omega-3 to omega-6 fatty acids may be as important to pregnant women as the absolute individual plasma levels of these fatty acids.

Nonetheless, in pregnancy, the real significance of eicosapentaenoic acid (EPA) may be related to its role in mediating DHA and arachidonic acid (AA) concentrations across the placenta rather than its production of the relatively less potent PGI3. Free fatty acids need to be bound for transfer to the fetal circulation. Selective transport across the human placenta for individual fatty acids has been suggested as a mechanism to explain greater concentrations of some PUFAs like DHA and AA in the fetal, rather than maternal, circulation. In this regard, the effect of EPA on mRNA expression of fatty acid transport proteins (FATPs) becomes important ²². EPA, but not DHA, has been positively correlated with mRNA expression of all membrane proteins. Thus, higher maternal EPA concentrations may increase FATP expression (FATP-4 in particular) that, in turn, has been shown to increase cord blood DHA levels ²². In addition, the free fatty acids need to be bound to fatty acid binding proteins (FABPs) in order to gain entry into placental and fetal cells. Because, as noted above, EPA has been positively correlated with mRNA expression of all membrane proteins, higher EPA concentrations also lead to increased expression of FABPs including B-FABP, which is strongly expressed in developing brain cells and has a strong affinity for DHA ²³.

Because only about 4% to 11% of DHA is retroconverted to EPA ²⁴, pregnant women who just take DHA supplements, without any dietary EPA, may be unable to produce the right balance of eicosanoids and may limit the transport and uptake of DHA into fetal cells ²⁴.

In the field of perinatal nutrition, polyunsaturated fatty acids (PUFAs) of the omega-3 and omega-6 groups have gained recent attention because of their important functions in fetal and newborn neurodevelopment and because of their roles in inflammation ²⁵, ²⁶, ²⁷.

Two PUFAs, arachidonic acid (AA) and docosahexaenoic acid (DHA), are critical to fetal and infant central nervous system (brain) growth and development ²⁵, ²⁸. Embedded in the cell membrane phospholipid, arachidonic acid (AA) is involved in cell signaling pathways and cell division, and serves as an inflammatory precursor for eicosanoids. The DHA concentration is high in retinal and brain membrane phospholipids, and it is involved in visual and neural function and neurotransmitter metabolism ²⁶. During the last trimester, the fetus accrues about 50 to 70 mg a day of omega-3 fatty acid, DHA ²⁹, ³⁰. Both maternal DHA intake and circulating DHA concentrations are important determinants of fetal blood concentrations of DHA ²⁷. Babies accrue DHA into the brain up until about 18 months of age ³¹, ³².

Although research into the specific pathways affected by these PUFAs is still in its infancy, there is enough understanding to draw conclusions and make recommendations about their dietary intake during the perinatal period.

Foods with DHA and EPA

The U.S. Department of Agriculture’s (USDA’s) Nutrient Database website ³³ lists the nutrient content of many foods with DHA (Docosahexaenoic acid) arranged by DHA nutrient content ³⁴ and by DHA food name ³⁵.

Table 2. Omega-3 Fatty Acid Foods EPA (Eicosapentaenoic acid) and DHA (Docosahexaenoic acid) – Fish and Seafood Sources

[Source ⁵]

Table 3. Other sources of Omega-3 Alpha-Linolenic Acid (ALA) – Non-Seafood Sources

[Source ³⁶]

The typical Western diet is deficient in omega-3 PUFAs, in general, and in DHA in particular. Although seafood is a good source of both DHA and EPA, concerns about mercury contamination have led to both fear and confusion about whether to recommend it during pregnancy. Both the Environmental Protection Agency and The American College of Obstetricians and Gynecologists recommend that women consume 12 ounces of seafood per week from low-mercury species:

• Shrimp 880 mg (320 mg DHA) ³⁷
• Salmon 620 mg (260 mg DHA) ³⁷
• Pollock 520 mg (360 mg DHA) ³⁷
• Catfish 340 mg (180 mg DHA) ³⁷
• Scallops 740 mg (360 mg DHA) ³⁷
• Sardines 2.2 g (1.2 g DHA) ³⁸
• Light tuna 380 mg (170 mg DHA) ³⁷

Avoid large predatory fish (e.g. marlin, pike, swordfish and shark), which are more likely to be contaminated with methylmercury.

[Source ³⁹]

For those seeking to avoid seafood, there are few nonsupplement options. Plant-based omega-3 fatty acids (ie, α-linolenic acid [ALA]), like flaxseed oil, are poorly converted to the biologically active omega-3 fatty acid EPA, and converts even less to DHA ²⁴, ⁴⁰. The range of conversion of Alpha-linolenic acid (ALA) to Eicosapentaenoic acid (EPA) is generally between 0.2% and 9%, although some authors have suggested that women of childbearing age may be able to convert up to 21% of their dietary ALA to EPA. Regardless of which conversion factor is correct, trying to obtain all omega-3 fatty acids from plant-based oils requires ingestion of too many fat calories.

Infant health and neurodevelopment

Numerous studies have examined the effects of maternal seafood and omega-3 intakes on infant birth weight, length of gestation, visual and cognitive development, and other infant health outcomes. High concentrations of DHA are present in the cellular membranes of the brain and retina ⁴¹, and DHA is important for fetal growth and development. The accumulation of DHA in the retina is complete by birth, whereas accumulation in the brain continues throughout the first 2 years after birth.

In 2016, Agency for Healthcare Research and Quality (AHRQ) published a review on the effects of omega-3 fatty acids on child and maternal health ⁴². This comprehensive report evaluated the findings from 95 randomized controlled trials and 48 prospective longitudinal studies and nested case-control studies. Most studies examined the effects of fish oil supplements or other DHA and EPA combinations in pregnant or breastfeeding women or of infant formula fortified with DHA plus arachidonic acid, an omega-6. The authors concluded that, except for small beneficial effects on infant birth weight and length of gestation, omega-3 supplementation or fortification has no consistent effects on infant health outcomes.

Recommendations from the Dietary Guidelines for Americans: The 2015–2020 Dietary Guidelines for Americans states that women who are pregnant or breastfeeding should consume 8–12 ounces of seafood per week, choosing from varieties that are higher in EPA and DHA and lower in methyl mercury, such as salmon, herring, sardines, and trout. These women should not consume certain types of fish, such as king mackerel, shark, swordfish, and tilefish that are high in methyl mercury, and they should limit the amount of white (albacore) tuna they consume to 6 ounces a week. The American Academy of Pediatrics has similar advice for breastfeeding women, recommending intakes of 200–300 mg DHA per day by consuming one to two servings of fish per week to guarantee a sufficient amount of DHA in breast milk ⁴³.

Most currently available infant formulas in the United States contain DHA and arachidonic acid. However, the authors of a paper published by the American Academy of Family Physicians and of two Cochrane reviews (one on full-term infants and one on preterm infants) have concluded that the evidence is insufficient to recommend the use of infant formulas that are supplemented with these fatty acids ⁴⁴, ⁴⁵, ⁴⁶.

DHA supplement

Fish oil supplements are commercially available from multiple companies. A typical fish oil supplement provides about 1,000 mg fish oil, the amount of EPA and DHA per capsule varies, but most contain one-third to one-half of these omega-3 fatty acids (eg, in a 1000-mg capsule, 300 or 500 mg would come from EPA and DHA) ¹. Although seafood contains varying levels of methyl mercury (a toxic heavy metal) ⁴⁷, omega-3 supplements have not been found to contain this contaminant because it is removed during processing and purification ⁴⁸. Cod liver oil is considered a less desirable source of EPA and DHA, because it is also rich in vitamin A, unlike other fish oils ¹. Long-term use of vitamin A has been associated with an increased risk of osteoporosis ⁴⁹.

Meaningful vegetarian sources of DHA are essentially limited to algae-derived DHA from Martek Biosciences (Columbia, MD) ¹. Using a strain of algae, Crypthecodinium cohnii, which is a naturally high producer of DHA, DHA oil is produced in US Food and Drug Administration-inspected, environmentally controlled manufacturing facilities. Although free of any environmental contaminants such as mercury, the oils do not contain any EPA and data demonstrating the benefits in pregnancy of DHA alone are lacking ¹.

Much of the interest in omega-3 fatty acid intake and pregnancy began in the early 1980s, when Danish investigators determined that women living on the Faroe Islands delivered babies that were 194 g heavier and had gestation lengths 4 days longer than babies born in Denmark ²⁰. The Faroese diet had substantially more omega-3 fatty acids and less omega-6 fatty acids than a Danish diet. Red blood cell fatty acid content (expressed as the ratio of omega-3 to omega-6) was significantly higher in the Faroese pregnant women than in Danish pregnant women ⁵⁰. From this study, the authors theorized that a Danish woman who adjusted her diet to increase her blood ratio of these fatty acids by 20% would expect to increase gestation 5.7 days ⁵⁰.

Following up on their earlier epidemiologic work, the same Danish group then randomized pregnant women at week 30 of gestation to either a fish oil supplement (2.7 g omega-3 fatty acids, of which 920 mg were DHA), olive oil, or no supplement ¹⁹. Women in the fish oil group had a gestational period 4 days longer than women taking either olive oil or no supplement. The babies born to the women in the fish oil group also weighed 107 g more than babies born to the women in the olive oil group, and 43 g more than those born to those mothers without supplementation. The supplemental amount of dietary omega-3 fatty acids used in this study was larger than a typical Danish diet, which only provided about 10% of this amount (ie, 270 mg of omega-3 fatty acids). Thus, it appeared that rather high amounts of omega-3 fatty acids need to be consumed to affect gestation and fetal weight.

The time of the most rapid neural and retinal development occurs in the second half of pregnancy, mainly during the third trimester. On this basis, supplementation of the maternal diet later in pregnancy with omega-3 fatty acids, especially DHA, was thought to be especially important ¹⁰, ¹⁴, ⁵¹. In a trial focused on the benefits of naturally occurring DHA from food, a sample of pregnant Inuit women living in Arctic Quebec was assessed ²¹. Maternal DHA blood concentrations were shown to be directly related to cord plasma phospholipid levels, and the correlation of the DHA/AA ratio in maternal and cord plasma was even stronger. In this study, higher DHA cord blood concentration was related to longer gestation, better visual acuity and mental and psychomotor skills at 6 months and 11 months, suggesting that raising DHA concentrations alone may independently yield some benefits ²¹. It must be noted that the Inuit population has a dietary intake of EPA and DHA that is higher than most other nations because of their regular intake of fish and marine animals. Such foods are also rich in EPA, but it was not measured.

A second study providing large amounts of DHA as a supplement explored its effects during pregnancy and, later, on fetal cognition ²⁷. From week 16 of gestation until delivery, healthy Canadian women (average age, 33 years) who were not taking supplemental fish oil capsules were randomized to 400 mg of algae-derived DHA or a blend of corn and soybean oil. The purpose of the study was to compare red blood cell DHA levels, dietary intakes of DHA and other omega-3 fatty acids, and infant visual acuity at 60 days of age. At week 36, DHA in the supplemented women was 32% higher than the control group, and no differences were found between the groups for EPA and AA, both of which decreased. Infants were 3 times more likely to have low visual acuity scores in the placebo group than the DHA group, indicating that the usual diet may have had insufficient DHA to maximize visual acuity in infants. In fact, omega-3 fatty acid deficiency, as measured by red blood cell DHA, was more prevalent in the control group than in the DHA-supplemented group.

DHA Benefits

Docosahexaenoic acid (DHA), as a fundamental constituent in cell membranes, is essential to the structure, maturation and function of the retina and the brain ⁵², ⁵³. DHA is mainly contained in aquatic products, especially in seafood. Dietary DHA intake is a major source to meet human body requirements, since humans only synthesize a limited amount of DHA from α-linolenic acid (ALA) ⁵⁴. It is widely acknowledged that pregnant and lactating women are more susceptible to DHA deficiency because they need to meet their own needs as well as those of the fetuses. Increased intake of DHA during pregnancy and lactation has been documented to benefit fetal and infant development ⁵⁵, ⁵⁶, ⁵⁷.

The availability and consumption of aquatic products plays an important role in DHA status. In a study ⁵⁸ conducted among women from four Tanzanian tribes differing in lifetime intakes of fish, Luxwolda et al. observed an obvious positive correlation between fish consumption and DHA levels ⁵⁸. DHA status may also vary across ethnicities. In a study ⁵⁹ comparing plasma DHA phospholipids between Dutch and ethnic minority pregnant women in Netherlands, van Eijsden et al. ⁵⁹ reported significant ethnic differences in maternal DHA status despite controlling for fish intake. Besides, in an earlier study ⁶⁰ involving women from Ecuador and four European countries with different baseline phospholipid DHA status, Otto et al. ⁶⁰ observed consistent decreases in the DHA weight percentage of total fatty acids as women progress from early pregnancy to delivery.

Babies fed with breast milk are known to have more mature visual skills and a higher IQ (intelligence quotient) than babies fed with formula milk. Unlike breast milk that contains high levels of long chain PUFA (e.g. DHA and AA), most infant formulae are known to only contain minimal amounts of long chain PUFA. The presence of docosahexaenoic acid (DHA) and arachidonic acid (AA) in human milk but not in infant formula, coupled with lower plasma and brain lipid contents of DHA in formula-fed than in breast-fed infants and reports of higher IQ in individuals who were breast-fed versus formula-fed as infants, suggest that exogenous DHA (and AA) may be essential for optimal development ⁶¹. Thus, since 1990, several studies have examined the impact of formulas containing DHA or DHA plus AA on visual function and neurodevelopmental outcome. Some of these studies have shown benefits but others have not. These results leave largely unanswered the question of whether these fatty acids are beneficial for either the term or preterm infant. However, evidence that preterm infants might benefit is somewhat more convincing than that for term infants. Despite the limited evidence for efficacy, formulas supplemented with DHA and AA are now available and appear to be safe.

In terms of feeding full-term babies with formula milk enriched with long chain polyunsaturated fatty acids (long chain PUFA e.g. DHA or EPA), this Cochrane review ⁶² analysed studies that compared outcomes of full-term babies (born at ≥ 37 weeks of pregnancy) who were given formula milk enriched with long chain polyunsaturated fatty acids versus outcomes of full-term babies fed formula milk without enrichment with long chain PUFA. Review authors found that full-term babies fed formula milk supplemented with long chain PUFA did not have better outcomes than were reported for full-term babies fed formula milk without long chain PUFA. Most of the included randomised clinical trials reported no beneficial effects or harms of long chain PUFA supplementation on neurodevelopmental outcomes of formula-fed full-term infants and no consistent beneficial effects on visual acuity. Routine supplementation of full-term infant milk formula with long chain PUFA cannot be recommended at this time ⁶².

It has been suggested that the relatively high levels of long chain PUFA found in breast milk may contribute to the higher IQ levels and visual skills. Some milk formulae are available with added long chain PUFA, usually as fish oil. In another 2016 Cochrane Review ⁶³ studies that compared the outcomes of premature babies (born at < 37 weeks of pregnancy) who were given formula milk enriched with long chain polyunsaturated fatty acids versus formula milk without enrichment with long chain PUFA were analysed. The researchers found that premature babies fed formula milk supplemented with long chain PUFA do not have better outcomes compared to those fed formula milk without long chain PUFA ⁶³.

Prenatal DHA and Pregnancy

According to this 2007 European Commission on Early Nutrition Programming Project ⁶⁴ pregnant and lactating women should aim to achieve an average dietary intake of at least 200 mg DHA per day can be reached with the consumption of one to two portions of sea fish per week, including oily fish such as herring, mackerel and salmon ⁶⁴. The European Food Safety Authority concluded that pregnant women eating up to two portions per week of fish are unlikely to exceed the provisional tolerable weekly intake for dioxin, dioxin-like compounds and contaminants such as methylmercury, polychlorinated biphenyls, brominated flame retardants, camphechlor and organotin ⁶⁴. However, particularly high levels of contamination are found in herring or wild salmon from the Baltic Sea and women of childbearing age should limit the consumption of Baltic Sea herring or wild salmon to no more than one portion per week ⁶⁴. Intakes of up to 1 g per day of DHA or 2·7 g/d Omega-3 long-chain PUFA have been used in randomized clinical trials without significant adverse effects; women of childbearing age should aim to consume one to two portions of sea fish per week, including oily fish ⁶⁴. Intake of the DHA precursor, α-linolenic acid (ALA), is far less effective with regard to DHA deposition in fetal brain than preformed DHA ⁶⁴. Intake of fish or other sources of long-chain Omega-3 fatty acids results in a slightly longer pregnancy duration; dietary inadequacies should be screened for during pregnancy and individual counselling be offered if needed.

The Omega-3 long chain-PUFA, DHA, must be deposited in appreciable amounts in the central nervous system during the perinatal brain growth spurt, as well as in other membrane-rich tissues. Fetal DHA accretion amounts to about 30–45 mg per day in the last trimester of gestation, while arachidonic acid (AA) accretion mainly occurs postnatally ⁶⁵, ⁶⁶. The pathways to form DHA from the precursor essential fatty acid, α-linolenic acid (ALA), exist in man (see Figure 4 above). The fractional conversion of α-linolenic acid (ALA) to Omega-3 long chain-PUFA may be greater in women than in men, which may contribute to meeting the demands of the fetus and the breast-fed neonate for DHA, but most evidence indicates that the overall contribution of α-linolenic acid (ALA) to DHA is limited; therefore, adequate intakes of preformed Omega-3 long chain-PUFA and in particular DHA, appear important for maintaining optimal tissue function ⁶⁷, ⁶⁸, ⁶⁹. In intrauterine growth-restricted pregnancies, indications for reduced placental and/or fetal conversion of precursor essential fatty acids to long chain-PUFA (DHA and EPA) have been reported ⁷⁰. Moreover, recent data indicate a considerable inter-individual variation in the ability to convert the precursor α-linolenic acid (ALA) to DHA, related to common polymorphisms in the human Δ-5 and Δ-6 desaturase genes FADS1 and FADS29. Preformed DHA is preferentially transferred across the human placenta to the fetus mediated by specific transfer proteins ⁷¹. In non-human primates, preformed dietary DHA is about an order of magnitude more efficient as a source for the neonatal brain accumulation of DHA than is α-linolenic acid ⁷².

The effects of supplementing pregnant women with Omega-3 long chain-PUFA from fish oil or single cell oils on pregnancy outcomes have been evaluated in a number of randomized controlled clinical trials, which provided daily DHA intakes ranging from 150–200 mg up to about 1200 mg/d, or up to 2·7 g total Omega-3 long chain-PUFA per day. Systematic evaluation of these studies in recent meta analyses revealed that Omega-3 long chain-PUFA prolonged gestation by a mean of 1·6 or 2·6 days in two independent analyses, respectively ⁷³, ⁷⁴, accompanied by a slight increase of birth weight by a mean 47 or 54 g, respectively ⁷³, ⁷⁴ and reduced the risk of preterm birth before 34 weeks of gestation by 31 % in all pregnancies ⁷⁴ or by 61 % in high-risk pregnancies ⁷⁵. Except for some reported discomfort associated with the intake of Omega-3 oil capsules, such as belching and unpleasant taste, no adverse effects were detected up to the highest intake of 2·7 g total Omega-3 long chain-PUFA per day tested in a randomized controlled trial in pregnancy.

Enhanced maternal dietary intakes of DHA increase fetal supply and lead to higher DHA concentrations in cord blood ⁷⁶. A higher DHA supply to the fetus during pregnancy and to the infant after birth was associated with beneficial effects on the development of visual acuity, cognitive functions and attention, maturity of sleep patterns, spontaneous motor activity, immune phenotypes in cohort studies and in a limited number of randomized clinical trials ⁷⁷, ⁷⁸, ⁷⁹. Based on the information available at this time, it is advisable that pregnant women aim at achieving an average intake of at least 200 mg DHA per day. Supplementation of lactating women with 200 mg DHA/d increased human milk DHA content by about 0·2 % fatty acids to a level considered desirable for infant outcomes ⁸⁰, ⁸¹. Therefore, an average dietary intake of at least 200 mg DHA/d appears to be also adequate during lactation.

Postnatal depression is a common condition that affects women and may impact on their babies. Common symptoms of postnatal depression include fluctuations in mood, mood changes, suicidal ideation and preoccupation with infant well-being ranging from over-concern to frank delusions. There is currently not much evidence regarding interventions that might prevent or treat postnatal depression. A diet lacking in certain vitamins, minerals or other nutrients (e.g. DHA, EPA) may cause postnatal depression in some women. Correcting this deficiency with dietary supplements might therefore prevent postnatal depression. In a large double-blind, multicenter, randomized controlled trial involving DHA and mother infant outcome conducted in 5 Australian maternity hospitals involving 2399 women who were less than 21 weeks’ gestation with singleton pregnancies ⁸². Women allocated to the DHA group were asked to consume three 500-mg/d capsules of DHA-rich fish oil concentrate, providing 800 mg/d of DHA and 100 mg/d of eicosapentaenoic acid (EPA, 20:5n-3; Incromega 500 TG); and women in the control group were asked to take three 500-mg/d vegetable oil capsules without DHA ⁸². The dose of 800 mg/d was chosen because this was above the estimated threshold associated with lower risk of depressed maternal mood and higher scores on developmental outcomes of children ⁸³, as well as being consistent with the estimated requirement to cover 97% of the population ⁸⁴. The vegetable oil capsules contained a blend of 3 nongenetically modified oils (rapeseed, sunflower, and palm) in equal proportions. This blend of oils was designed to match the polyunsaturated, monounsaturated, and saturated fatty acid profile of the average Australian diet ⁸⁵. Women were asked to take their assigned capsules daily, from study entry until birth of their child. All capsules were similar in size, shape, and color. In addition, 694 children (95.6% of those selected for follow-up) were assessed at 18 months.

The results were the percentage of women reporting high levels of depressive symptoms during the first 6 months postpartum did not differ between the DHA and control groups ⁸². Depressive symptoms were more common among women with a previous or current diagnosis of depression at trial entry but did not differ between groups ⁸². The percentage of women with a new medical diagnosis for depression during the trial or a diagnosis requiring treatment also did not differ between groups ⁸².

Mean cognitive scores of children from women allocated to the DHA group did not differ from mean scores of children of women from the control group, although fewer children from the DHA group had cognitive scores indicating delayed cognitive development compared with controls ⁸². Overall, mean language scores also did not differ between groups; however, a significant treatment × sex interaction indicated a differential response of boys and girls. Girls from the DHA group had a lower mean language score than girls from the control group, as well as an increased risk of delayed language development, and the response of boys did not differ between groups ⁸². For the secondary developmental outcomes, motor development, social-emotional behavior, and adaptive behavior did not differ between groups overall, although girls exposed to DHA in utero had poorer mean adaptive behavior scores than girls from the control group ⁸².

The secondary clinical outcomes of the infants – there were fewer very preterm births (<34 weeks’ gestation) in the DHA group compared with the control group, but there were more postterm births requiring obstetric intervention (inductions or cesarean deliveries) in the DHA group compared with the control group ⁸². Mean birth weight was 68 g heavier and fewer infants were of low birth weight in the DHA group compared with the control group ⁸². However, mean birth weight z scores (corrected for gestational age and sex) did not differ between groups, indicating that group differences in birth size were largely a function of gestational age at birth ⁸².

In summary, the use of DHA-rich fish oil capsules compared with vegetable oil capsules during pregnancy did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood ⁸².

Furthermore, in a 2013 Cochrane Review ⁸⁶, the study authors stated there is insufficient evidence to conclude that selenium, DHA or EPA prevent postnatal depression ⁸⁶. There is currently no evidence to recommend any other dietary supplement for prevention of postnatal depression.

Summary

Women of childbearing age can meet the recommended intake of DHA (at least 200 mg DHA/day) by consuming one to two portions of sea fish per week, including oily fish, which is a good source of Omega-3 long chain-PUFA. This intake of oily fish rarely exceeds the tolerable intake of environmental contaminants. Dietary fish should be selected from a wide range of species without undue preference for large predatory fish (e.g. marlin, pike, swordfish and shark), which are more likely to be contaminated with methylmercury.

Intake of the precursor, α-linolenic acid (ALA), is far less effective with regard to DHA deposition in fetal brain than the intake of preformed DHA.

There is no evidence that women of childbearing age whose dietary intake of linoleic acid (LA) is adequate, need an additional dietary intake of arachidonic acid (AA).

Some studies have shown that maternal intake of fish, fish oils or Omega-3 long chain-PUFA results in a slightly longer duration of gestation ⁸⁷, a somewhat higher birth weight (greater birth size) and a reduced risk of early preterm delivery ⁸⁸. The clinical importance of such effects with regard to overall infant health and development of most infants has not been fully elucidated and is subject to further investigation.

The amount of Omega-3 long chain-PUFA supplementation (DHA plus EPA) in the published trials ranges from 100 mg to 3.3 grams per day. Studies did not identify any serious safety concerns related to DHA supplementation for mother or newborn.

There is currently no evidence to recommend any other dietary supplement for prevention of postnatal depression. The use of DHA-rich fish oil capsules during pregnancy did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood. Furthermore, brain development and function is influenced by many variables other than DHA. To add complexity, infant development is a distribution in which an individual’s potential is unknown.

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