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A fishy recommendation: omega-3 fatty acidintake in pregnancy Department of Obstetrics and Gynecology, Faculty of Medicine, University of Alberta, Edmonton, Alberta, CanadaCorrespondence: Dr SJ Genuis, University of Alberta, 2935-66 Street, Edmonton, Alberta, Canada T6K 4C1. Email sgenuis@ualberta.ca Please cite this paper as: Genuis S. A fishy recommendation: omega-3 fatty acid intake in pregnancy. BJOG 2008;115:1–4.
offspring for diabetes,16 asthma,17 adverse bone health,18and multiple sclerosis19 illustrate the truism that the human With recent concern about aquatic contamination from being requires specific nutrients during gestation to carry out potential teratogens including heavy metals, dioxins, pharma- the molecular processes within cells and tissues, processes ceutical residues, polychlorinated biphenyls (PCBs), and syn- which on the macroscale influence both maternal physiology thetic estrogens,1–6 some public health agencies throughout and fetal development. Considerable attention has recently the world have recommended limiting gestational fish con- focused on the role of EFAs in maternal and fetal metabolism.
sumption to minimise fetal harm associated with toxicantexposure.7 Conversely, a well-publicised research paper inLancet concluded that adequate seafood consumption in pregnancy correlates with improved child development andthat ‘advice to limit seafood consumption could actually be EFAs refer to lipids that cannot be synthesised within the detrimental’.8 This commentary will consider the issue of body and must be ingested to meet metabolic demands.
maternal fish consumption in the context of recent medical The two families of essential lipids—omega-3 fatty acids literature on nutrition and essential fatty acids (EFAs).
(v3FAs) and omega-6 fatty acids (v6FAs)—are required for With discussion of intricate laparoscopic techniques, physiological functions including oxygen transport, energy avant-garde reproductive interventions, complex microsur- storage, cell membrane function, and regulation of inflam- gery, and epigenetic therapies, many medical practitioners mation and cell proliferation.20,21 In pregnancy, EFAs are find the practice of dietary or nutritional therapy to be dull, required for early development of the fetal-placental unit;22 alternative, and perhaps simplistic medicine. Exploration of docosahexaenoic acid (DHA), a type of v3FA commonly the aetiological factors contributing to the global escalation in derived from seafood, is vital for maternal homeostasis, as chronic disease,9 however, has revealed that some contempo- well as fetal brain and retinal development throughout the rary ill health results from nutritional compromise.10 Further- more, recent research demonstrates that certain obstetric and Various studies have demonstrated that EFA deficiency as paediatric afflictions might effectively be prevented by pro- well as unbalanced consumption of v3FAs and v6FAs may vision during pregnancy of the nutrients required for optimal be significant to health outcomes.26 With an overall 80% decline in v3FA intake in the past century,6,27 combined with The correlation between deficient folate and neural tube a noteworthy increase in v6FA intake, epidemiological defects11 (NTDs) previously prompted widespread pericon- research suggests that EFA malnutrition may be a determinant ceptional supplementation and recent concerns about poten- of several chronic and degenerative disease states.20,26 Various tial fetal sequelae (including cleft palate)12 of maternal biotin recent papers and meta-analyses report an increased risk of deficiency13 as well as considerable risk for NTDs with low a variety of condition such as heart disease,28 rheumatoid maternal vitamin B12 status14 have fuelled intensified re- arthritis,29 breast cancer,30 hypertension,31 osteoporosis,32 search on the link between gestational nutrient requirements and neurological33 and psychiatric disease34 in association and maternal and fetal outcome. Correlations including with inadequate v3FA consumption. Maternal and fetal those of maternal selenium levels with pre-eclampsia15 and research has also begun to evaluate the consequences of maternal vitamin D status with subsequent risk in the ª 2008 The Author Journal compilation ª RCOG 2008 BJOG An International Journal of Obstetrics and Gynaecology behaviour,51 and less risk of metabolic disorders such as type I diabetes in the developing offspring.52 In review, there isabundant evidence in the medical literature that links ade- It has been hypothesised that sufficient gestational v3FA quate gestational fatty acid status with maternal and fetal intake may diminish the likelihood of preterm labour by the downregulation of prostaglandin formation.35 Juxtaposedwith recent evidence that inadequate consumption of v3FAs significantly increases the likelihood of early labour,36 an epi- demiological study has reported a marked rise in pretermbirth among white American women from 1981 to 1998.37 To secure safe and appropriate v3FA gestational intake, two Furthermore, a prospective cohort study demonstrated that principles merit consideration. Marine sources of v3FAs women who avoided seafood had a 7.1% incidence of preterm contain required DHA, while plant foods generally do not; birth compared with a 1.9% risk for those eating fish once conversion from plant source v3FAs to DHA is possible weekly.38 In addition, maternal consumption of cod liver oil but requires energy and enzymatic availability. As v3FAs and increased v3FA:v6FA intake ratio have been associated and v6FAs use the same enzymes, dietary intake ratio of with longer gestations and higher birthweights,35,39,40 except these lipids can determine enzymatic availability. Accord- in women with high pre-existing levels of v3FAs.35 Whether ingly, while some pregnant women produce sufficient DHA the results from these interesting studies should change our through biochemical conversion from plant source v3FAs, clinical practice remains uncertain.
direct DHA from fish intake secures provision of this required Hypertension complicates about 6% of pregnancies in the developed world. A cross-sectional case–control study found As a result of multiple potential teratogens contaminating that pregnant women with low levels of v3FAs were 7.6 times seafood sources,1–6 however, some authors warn about risks more likely to have pre-eclampsia than those with high levels associated with gestational seafood intake. With potentially of this EFA41 and that a 46% risk reduction for pre-eclampsia long induction times from toxicant exposure to ultimate could be achieved by a moderate increase in the proportion of outcomes53 [as in the diethylstilbestrol (DES) tragedy], with v3FAs consumed.41 While meta-analytical reviews confirm insufficient research on the long-term impact of many a dose-dependent relationship between v3FAs intake and contemporary aquatic contaminants (acting in isolation or blood pressure outside pregnancy,30,41 recent evidence sug- synergistically with other pollutants), and with pronounced gests that blood pressure control later in life may also be vulnerability of the fetus to seemingly minuscule levels of affected negatively by inadequate maternal and neonatal toxicants,53 debate continues as to whether risks from EFA intake of v3FAs.42 While many studies show significant insufficiency outweigh the risks of harm from seafood toxi- benefit in relation to hypertension, a controlled trial of cants. In response, some have suggested that supplementation supplementation in selected high-risk pregnancies found with fish oil rather than seafood consumption might be a pre- that additional v3FA intake was associated with reduced ferred approach to providing required DHA. Recent research, recurrence risk for preterm delivery but had no impact on however, has challenged this approach.
recurrence risks for intrauterine growth restriction or preg- Most work examining fish oil use in pregnancy demon- strates benefit; a few recent studies, however, fail to confirm The demonstrated correlation between lower gestational benefit and some outcomes appear to suggest harm.54,55 A seafood consumption and higher rates of postpartum depres- major confounder in current work, however, is that oil pre- sion44 suggests that individual v3FA indices may also be pared from fish liver (the major organ of detoxification) is a determinant of postpartum mood status.45,46 Possibly asso- often contaminated with the same toxicants including heavy ciated with the limited seafood intake in North America, the metals23 found in source fish. Accordingly, consumers of reg- incidence of postpartum depression is in the range of 12% ular fish oil consume toxicants that may affect physiological compared with about 2% in Japan where fish consumption is processes and influence metabolic outcomes. Methyl mer- high44 (although major cultural differences in the way the two cury, for example, is a common aquatic contaminant and societies are organised may also be important). Furthermore, can induce hypertension in animals56—this may account for low DHA in breast milk and maternal red cells, resulting from adverse outcomes, such as gestational hypertension in con- low gestational intake of EFAs,47 are commonly found in sumers of regular fish oil.55 Furthermore, some toxicants can impair or modify absorption, utilisation, and metabolism of Maternal v3FA status also appears to correlate with fetal nutrients potentially resulting in adverse sequelae.
outcome. Ensuring a sufficiency of v3FAs for women during To address the toxicity concern, however, gestational EFA pregnancy and lactation has been correlated with enhanced requirements can be secured with avoidance of toxic exposure cognitive and behavioural functioning,48–50 improved sleep by replacing gestational seafood intake with regular ingestion ª 2008 The Author Journal compilation ª RCOG 2008 BJOG An International Journal of Obstetrics and Gynaecology of plant source v3FAs and supplementation with purified fish 7 US Department of Health and Human Services UEPA. What you need oil.57,58 Through distillation and subsequent toxicological to know about mercury in fish and shellfish. EPA and FDA advice forwomen who might become pregnant, women who are pregnant, testing, purified fish oil preparations are available. As well nursing mothers, and young children. 2004 [www.cfsan.fda.gov/;dms/ as obviating patient hazard, toxicant confounding in research admehg3.html]. Accessed 9 March 2007.
can be precluded by use of purified preparations.
8 Hibbeln JR, Davis JM, Steer C, Emmett P, Rogers I, William C, et al.
Maternal seafood consumption in pregnancy and neurodevelopmentaloutcomes in childhood (ALSPAC study): an observational cohort study.
Lancet 2007;369:578–85.
9 Horton R. The neglected epidemic of chronic disease. Lancet 2005; The recent medical and scientific literature correlating micro- 10 Genuis SJ. Nutritional transition: a determinant of global health.
nutrient and dietary transitions with health sequelae makes it J Epidemiol Community Health 2005;59:615–17.
evident that nutritional status is a major determinant of 11 Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube health and wellbeing throughout life, including intrauterine defects by periconceptional vitamin supplementation. N Engl J Med1992;327:1832–5.
development. Regardless of beneficial outcomes in research or 12 University of Arkansas for Medical S. UAMS Leads Search for Answers epidemiological study, however, medical history has repeat- on Cleft Palate, Other Biotin-related Birth Defects. 2006 [www.uams.
edly demonstrated that translating new ideas and research edu/newsbureau/2003/January/biotinbirthdefects.htm]. Accessed 3 findings into clinical practice is generally a slow process.59 It often takes a generation—corresponding to the time required 13 Mock DM, Quirk JG, Mock NI. Marginal biotin deficiency during nor- mal pregnancy. Am J Clin Nutr 2002;75:295–9.
for new trainees untainted by status quo ideas and biases to 14 Ray JG, Wyatt PR, Thompson MD, Vermeulen MJ, Meier C, Wong PY, achieve positions of influence—before innovative clinical pat- et al. Vitamin B12 and the risk of neural tube defects in a folic-acid- terns emerge. While concerns about gestational folate defi- fortified population. Epidemiology 2007;18:362–6.
ciency were expressed in 1976,60 for example, it took two 15 Rayman MP, Bode P, Redman CW. Low selenium status is associ- decades before routine supplementation was widespread.
ated with the occurrence of the pregnancy disease preeclampsia inwomen from the United Kingdom. Am J Obstet Gynecol 2003;189: Research confirms the need for essential v3FAs in preg- nancy, and population analyses suggest that deficiency is 16 Fronczak CM, Baron AE, Chase HP, Ross C, Brady HL, Hoffman M, et al.
common. Accordingly, it is important that providers of In utero dietary exposures and risk of islet autoimmunity in children.
maternity care be familiar with principles of clinical nutrition and possess the necessary tools to assess and manage concerns 17 Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, Rich-Edward JW, Weiss ST, Gold DR, et al. Maternal intake of vitamin D during pregnancy and relating to nutritional health. In keeping with extensive epi- risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr 2007; demiological evidence linking obstetric and paediatric out- comes with gestational dietary habits, it is suggested that 18 Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, obstetricians and midwives should discuss the importance et al. Maternal vitamin D status during pregnancy and childhood bone of a good diet with pregnant women and that in the absence mass at age 9 years: a longitudinal study. Lancet 2006;367:36–43.
19 Chaudhuri A. Why we should offer routine vitamin D supplementation of measured maternal v3FAs levels, the plant source EFAs be in pregnancy and childhood to prevent multiple sclerosis. Med Hypoth- regularly consumed during pregnancy and pure fish oil sup- plements be explored as a means to provide the necessary 20 Simopoulos AP. Essential fatty acids in health and chronic diseases.
DHA required for optimal maternal and fetal outcome. j 21 Bralley JA, Lord RS. Laboratory Evaluations in Molecular Medicine: Nutrients, Toxicants, and Cell Regulators. Norcross, GA: The Institutefor Advances in Molecular Medicine, 2005.
22 Crawford MA, Doyle W, Drury P, Lennon A, Costeloe K, Leighfield M.
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3 Olsen SF. Mercury, PCB, and now eicosapentaenoic acid: still another 25 Wainwright PE. Dietary essential fatty acids and brain function: a devel- reason why pregnant women should be concerned about eating sea- opmental perspective on mechanisms. Proc Nutr Soc 2002;61:61–9.
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26 Simopoulos AP. The importance of the ratio of omega-6/omega-3 4 Sehmer J. Mercury in seafood. CMAJ 2002;167:122, 124.
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5 Heberer T. Occurrence, fate, and removal of pharmaceutical residues in 27 Simopoulos AP. n-3 fatty acids and human health: defining strategies the aquatic environment: a review of recent research data. Toxicol Lett for public policy. Lipids 2001;36 (Suppl):S83–9.
28 Bucher HC, Hengstler P, Schindler C, Meier G. N-3 polyunsaturated 6 Saldeen T. Fish Oil and Health. Uppsala, Sweden: Swede Health Press, fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials. Am J Med 2002;112:298–304.
ª 2008 The Author Journal compilation ª RCOG 2008 BJOG An International Journal of Obstetrics and Gynaecology 29 Kremer JM, Lawrence DA, Jubiz W, DiGiacomo R, Rynes R, Bartholomew 45 Makrides M, Crowther CA, Gibson RA, Gibson RS, Skeaff CM. Doco- LE, et al. Dietary fish oil and olive oil supplementation in patients with sahexaenoic acid and post-partum depression—is there a link? Asia rheumatoid arthritis. Clinical and immunologic effects. Arthritis Rheum Pac J Clin Nutr 2003;12 (Suppl):S37.
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33 Morris MC, Evans DA, Bienias JL, Tagney CC, Bennett DA, Wilson RS, 49 Willatts P. Long chain polyunsaturated fatty acids improve cognitive et al. Consumption of fish and n-3 fatty acids and risk of incident development. J Fam Health Care 2002;12(6 Suppl):5.
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50 Helland IB, Smith L, Saarem K, Saugstad OD, Drevon CA. Maternal 34 Stoll AL, Severus WE, Freeman MP, Reuter S, Zboyan HA, Diamond E, supplementation with very-long-chain n-3 fatty acids during preg- et al. Omega 3 fatty acids in bipolar disorder: a preliminary double- nancy and lactation augments children’s IQ at 4 years of age. Pediatrics blind, placebo-controlled trial. Arch Gen Psychiatry 1999;56:407–12.
35 Olsen SF, Hansen HS, Sommer S, Jensen B, Sørensen TI, Secher NJ, et al.
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36 McGregor JA, Allen KG, Harris MA, Reece M, Wheeler M, French JI, 52 Stene LC, Ulriksen J, Magnus P, Joner G. Use of cod liver oil during et al. The omega-3 story: nutritional prevention of preterm birth and pregnancy associated with lower risk of type I diabetes in the offspring.
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ª 2008 The Author Journal compilation ª RCOG 2008 BJOG An International Journal of Obstetrics and Gynaecology

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