DHA is the most important structural fatty acid in brain and eye. Daily some 75 mg DHA are pumped across the placenta to build up the fetus’ brain and eyes in the last three months of pregnancy at the mothers expense (Brenna u. Carlson, 2014). Specific proteins in the placenta actively and selectively transport DHA (Dunstan et al, 2004, Larqué et al, 2011). According to in vivo kinetics, this transport of DHA is regulated, so that DHA will reach approximately 9% in fetal erythrocytes, with EPA accounting for another 1.5 to 2.5% (Dunstan et al, 2004). Many scientific societies recommend a daily intake of at least 200 mg DHA during pregnancy (http://www.dge.de/wissenschaft/referenzwerte/fett/; Koletzko et al 2008). The recommendation supports an adequate brain structure, and adequate complex brain function (details below). The scientific societies recommend to diagnose deficits in nutrition early in pregnancy and act upon the results.

According to our measurements, more than 75% of the population have a HS-Omega-3 Index below the target range of 8 – 11% (von Schacky, 2014), which also applies to pregnant women. Therefore, we think that the HS-Omega-3 Index should be determined before or early in pregnancy, in order to detect a deficit in EPA and/or DHA. There is a substantial body of evidence demonstrating that pregnancies without a deficit in EPA and/or DHA have a better course and a better outcome for mother and child. This body of evidence is based on randomized intervention trials with EPA and/or DHA in pregnant women, and will be briefly presented here.

Duration of pregnancy: A systematic analysis of randomized intervention trials, comprising 1278 newborns, demonstrated that supplementation with EPA and DHA prolonged pregnancy by 1.57 days (95%CI: 0,35 – 2.78 d, p=0.01), and increased head circumference by 0.26 cm (95%CI 0.02 – 0.49, p=0.03)(Szajewaska et al. 2006). In a Cochrane-analysis, fish oil prolonged pregnancy by 2.6 days (95 % CI 1.03- 4.07), and increased birth weight slightly (47 g, 95 % CI 1 g – 93 g). In a more recently published meta-analysis, birth weight of the child was 71g higher and pregnancy 4.5 days longer (Salvig & Lamont, 2011). This was also found in a recent intervention trial (Carlson et al, 2013).

Premature birth: According to a Cochrane-analysis of 6 randomized intervention trials with omega-3 fatty acids (2783 pregnancies), premature birth occurred less frequently in women supplementing EPA plus DHA (RR 0,69, CI 0.49-0.99), than in the control groups (Makrides et al, 2006). A more recent meta-analysis of intervention trials had a similar result: low risk for birth before week 37 of gestation (RR 0.61, 95%CI 0.40 – 0.93; p<0.05), and a substantially lower risk before week 34 (RR 0,34, 95%CI 0.09 – 0.95) (Salvig & Lamont, 2011).

Pre-eclampsia: High levels of EPA and DHA in erythrocytes and plasma correlate with a low risk for hypertension and pre-eclampsia in pregnancy, as found in most, but not all epidemiologic studies (Brenna et al 2009, Qiu et al, 2006).

Post-partum depression: Low levels or low intake of EPA and DHA are associated with depression in pregnancy and childbed (Borja-Hart et al, 2010). Of seven intervention trials aiming at prevention of post-partum depression, three were positive (Borja-Hart et al, 2010). The trials were small, however (Borja-Hart et al, 2010). Meta-analyses comprising epidemiologic studies and intervention trials saw no clear-cut effect (Wojcicki & Heyman, 2011; Parker et al, 2015). Nevertheless, an early start and a dose of 2 g / day was recommended for future trials (Wojcicki & Heyman, 2011). The largest intervention trial ever conducted in pregnant women saw post-partum depression not reduced (Makrides et al, 2010). However, in more than 80% of participants levels overlapped between verum and placebo groups (Muhlhausler et al, 2014) – a typical phenomenon resulting from conventional trial design (discussed in more detail in the general part of this website). Recently, an intervention trial demonstrated a larger effect in verum than in placebo (Kaviani et al, 2014). Safety, tolerability and lack of alternatives make intervention trials with omega-3’s attractive in the future.

Many randomized controlled intervention trials investigated supplementing the diet of pregnant women with omega-3 fatty acids in doses from 0.13 – 3.3 g EPA plus DHA / day (mostly around 2 g / day) in comparison to placebo (Koletzko et al, 2007, Brenna et al, 2009, Carlson 2009, Innis 2008). Parameters representative for complex brain function, like visual acuity, attention spans, eye – hand coordination, problem solving behavior, and other were improved in children, whose mothers had verum supplements in pregnancy (Koletzko et al, 2007, Brenna et al, 2009, Carlson 2009, Innis 2008). The improved brain functions correlated with levels of EPA and DHA in the mother (if assessed). If pregnant women had higher levels of EPA plus DHA, the intelligence quotient of their children was higher at age seven (in comparison to mothers with lower levels, Brenna et al, 2009, Helland et al, 2008).

Other parameters found improved by supplementation with EPA and DHA in pregnancy were heart rate variability and sleep duration (Gustafson et al, 2013).
Allergies, colds and inflammatory diseases early in life
In a randomized trial, food allergies were less frequent in children of mothers having supplemented EPA plus DHA in pregnancy, in comparison to controls (Furuhjelm et al, 2009). Fewer and shorter colds were observed in children of mothers having supplemented EPA plus DHA in pregnancy, as compared to controls (Imhoff-Kunsch et al, 2011, Escamilla-Nuñez et al, 2011). Supplementing EPA plus DHA in pregnancy also reduced respiratory allergies and atopic eczema in the children (Palmer et al, 2012). Reduced tendency towards allergies and a less severe course of respiratory infections further support the supplementation with EPA plus DHA in pregnancy. We suggest to target the supplementation towards a HS-Omega-3 Index between 8 and 11%.

Bouwstra H, Dijck-Brouwer DAJ, Wildeman JAL, Tjoonk HM, van der Heide JC, Boersma ER, Muskiet FAJ, Hadders-Algra M. Long-chain polyunsaturated fatty acids have a positive effe on the quality of general movements of healthy term infants. Am J Clin Nutr 2003;78:313-8
Brenna JT, Lapillonne A. Background paper on fat and fatty acid requirements during pregnancy and lactation. Ann Nutr Metab. 2009;55(1-3):97-122
Brenna JT, Carlson SE. Docosahexaenoic acid and human brain development: Evidence that a dietary supply is needed for optimal development. J Hum Evol. 2014 Dec;77:99-106.
Carlson SE, Colombo J, Gajewski BJ, Gustafson KM, Mundy D, Yeast J, Georgieff MK, Markley LA, Kerling EH, Shaddy DJ. DHA supplementation and pregnancy outcomes. Am J Clin Nutr. 2013;97:808-15.
Dunstan JA, Mori TA, Barden A, Beilin LJ, Holt PG, Calder PC, Taylor AL, Prescott SL. Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and fetal erythrocyte fatty acid composition. Eur J Clin Nutr. 2004;58:429-37
Dunstan JA, Simmer K, Dixon G, Prescott SL. Cognitive assessment at 2 ½ years following fish oil supplementation in pregnancy: a randomized controlled trial. Arch Dis Child Fetal Neonatal Ed 2008;93:F45-50
Escamilla-Nuñez MC, Barraza-Villarreal A, Hernández-Cadena L, Navarro-Olivos E, Sly PD, Romieu I. Omega-3 fatty acid supplementation during pregnancy and respiratory symptoms in children. Chest. 2014 Aug;146(2):373-82
Gustafson KM, Carlson SE, Colombo J, Yeh HW, Shaddy DJ, Li S, Kerling EH. Effects of docosahexaenoic acid supplementation during pregnancy on fetal heart rate and variability: a randomized clinical trial. Prostaglandins Leukot Essent Fatty Acids. 2013 May;88(5):331-8.
Harris WS, Connor WE, Lindsey S.Will dietary omega-3 fatty acids change the composition of human milk? Am J Clin Nutr. 1984;40:780-5
Harsløf LB, Larsen LH, Ritz C, Hellgren LI, Michaelsen KF, Vogel U, Lauritzen L. FADS genotype and diet are important determinants of DHA status: a cross-sectional study in Danish infants. Am J Clin Nutr. 2013 Jun;97(6):1403-10
Helland IB, Smith L, Saarem K, Saugsted OD, Drevon CA. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children’s IQ at 4 years of age.Pediatrics 2003; 111:e39-44
Hibbeln JR. Seafood consumption, the DHA content of mothers’ milk and prevalence rates of postpartum depression: a cross-national, ecological analysis. J Affect Disord 2002; 69:15
Imhoff-Kunsch B, Stein AD, Martorell R, Parra-Cabrera S, Romieu I, Ramakrishnan U. Prenatal docosahexaenoic acid supplementation and infant morbidity: randomized controlled trial. Pediatrics. 2011 Sep;128(3):e505-12
Innis SM. Impact of maternal diet on human milk composition and neurological development of infants. Am J Clin Nutr. 2014 Mar;99(3):734S-41S Review
Jayawant S, Rawlinson A, Gibbon F, Price J, Schulte J, Sharples P, Sibert JR, Kemp AM. Subdural haemorrhages in infants: population based study. BMJ. 1998;317:1558-61
Jensen CL. Effect of n-3 fatty acids during pregnancy and lactation. Am J Clin Nutr 2006;83(Suppl)1452S-7S
Kaviani M, Saniee L, Azima S, Sharif F, Sayadi M. The Effect of Omega-3 Fatty Acid Supplementation on Maternal Depression during Pregnancy: A Double Blind Randomized Controlled Clinical Trial. Int J Community Based Nurs Midwifery. 2014 Jul;2(3):142-7.
Koletzko B, Lien E, Agostoni C, Böhles H, Campoy C, Cetin I, Decsi T, Dudenhausen JW, Dupont C, Forsyth S, Hoesli I, Holzgreve W, Lapillonne A, Putet G, Secher NJ, Symonds M, Szajewska H, Willatts P, Uauy R. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J Perinat Med. 2008;36:5-14
Larqué E, Demmelmair H, Gil-Sánchez A, Prieto-Sánchez MT, Blanco JE, Pagán A, Faber FL, Zamora S, Parrilla JJ, Koletzko B. Placental transfer of fatty acids and fetal implications. Am J Clin Nutr. 2011 Dec;94(6 Suppl):1908S-1913S
Makrides M, Duley L, Olsen SF. Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterine growth restriction. Cochrane Database Syst Rev 2006;3:CD003402
Makrides M, Gibson RA, McPhee AJ, Yelland L, Quinlivan J, Ryan P; DOMInO Investigative Team. Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial. JAMA. 2010;304:1675-83.
Matsuzaka T, Yoshinaga M, Tsuji Y, Yasunaga A, Mori K.. Incidence and causes of intracranial hemorrhage in infancy: a prospective surveillance study after vitamin K prophylaxis. Brain Dev. 1989;11:384-8
Meldrum SJ, D’Vaz N, Simmer K, Dunstan JA, Hird K, Prescott SL. Effects of high-dose fish oil supplementation during early infancy on neurodevelopment and language: a randomised controlled trial. Br J Nutr. 2012 Oct 28;108(8):1443-54.
Muhlhausler BS, Gibson RA, Yelland LN, Makrides M. Heterogeneity in cord blood DHA concentration: towards an explanation. Prostaglandins Leukot Essent Fatty Acids. 2014 Oct;91(4):135-40.
Olsen SF, Osterdal ML, Salvig JD, Weber T, Tabor A, Secher NJ. Duration of pregnancy in relation to fish oil supplementation and habitual fish intake: a randomised clinical trial with fish oil. Eur J Clin Nutr 2007;61:976-85
Palmer DJ, Sullivan T, Gold MS, Prescott SL, Heddle R, Gibson RA, Makrides M. Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants’ allergies in first year of life: randomised controlled trial. BMJ. 2012 Jan 30;344:e184
Parker G, Hegarty B, Granville-Smith I, Ho J, Paterson A, Gokiert A, Hadzi-Pavlovic D. Is essential fatty acid status in late pregnancy predictive of post-natal depression? Acta Psychiatr Scand. 2015;131:148-56.
Qiu C, Sanchez SE, Larrabure G, David R, Bralley JA, Williams MA. Erythrocyte omega-3 and omega-6 polyunsaturated fatty acids and preeclampsia risk in Peruvian women. Arch Gynecol Obstet. 2006;274:97-103
Salvig JD, Lamont RF. Evidence regarding an effect of marine n-3 fatty acids on preterm birth: a systematic review and meta-analysis. Acta Obstet Gynecol Scand. 2011 Aug;90(8):825-38
Szajewaska H, Horvath A, Koletzko B. Effect of n-3 long-chain polyunsaturated fatty acid supplementation of women with low-risk pregnancies on pregnancy outcomes and growth measures at birth: a meta-analysis of randomized controlled trials. Am J Clin Nutr 2006;83:1337-44
von Schacky C. Schwangerschaft, kindliche Entwicklung, Omega-3-Fettsäuren und HS-Omega-3 Index. J Frauengesundheit 2010;3:10-21.
Willatts P, Forsyth S, Agostoni C, Casaer P, Riva E, Boehm G. Effects of long-chain PUFA supplementation in infant formula on cognitive function in later childhood. Am J Clin Nutr. 2013 Aug;98(2):536S-42S.