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.
n-6 and n-3 fatty acids during early human development. J Intern Med
1 Bjerregaard P, Hansen JC. Organochlorines and heavy metals in preg-
nant women from the Disko Bay area in Greenland. Sci Total Environ
23 Saldeen P, Saldeen T. Women and omega-3 fatty acids. Obstet Gynecol
2 Matthiessen P, Sumpter JP. Effects of estrogenic substances in the
24 Nettleton JA. Are n-3 fatty acids essential nutrients for fetal and infant
aquatic environment. EXS 1998;86:319–35.
development? J Am Diet Assoc 1993;93:58–64.
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.
food? Int J Epidemiol 2001;30:1279–80.
26 Simopoulos AP. The importance of the ratio of omega-6/omega-3
4 Sehmer J. Mercury in seafood. CMAJ 2002;167:122, 124.
essential fatty acids. Biomed Pharmacother 2002;56:365–79.
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.
46 Rees AM, Austin MP, Parker G. Role of omega-3 fatty acids as a treat-
30 Maillard V, Bougnoux P, Ferrari P, Jourdan ML, Pinault M, Lavillonnie`re F,
ment for depression in the perinatal period. Aust N Z J Psychiatry 2005;
et al.N-3 and N-6 fatty acids in breast adipose tissue and relative risk of
breast cancer in a case-control study in tours, France. Int J Cancer
47 Maes M, Christophe A, Delanghe J, Altamura C, Neels H, Meltzer HY.
Lowered omega3 polyunsaturated fatty acids in serum phospholipids
31 Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ. Blood pres-
and cholesteryl esters of depressed patients. Psychiatry Res 1999;85:
sure response to fish oil supplementation: metaregression analysis of
randomized trials. J Hypertens 2002;20:1493–9.
48 McCann JC, Ames BN. Is docosahexaenoic acid, an n-3 long-chain
32 Weiss LA, Barrett-Connor E, von Muhlen D. Ratio of n-6 to n-3 fatty
polyunsaturated fatty acid, required for development of normal brain
acids and bone mineral density in older adults: the Rancho Bernardo
function? An overview of evidence from cognitive and behavioral tests
study. Am J Clin Nutr 2005;81:934–8.
in humans and animals. Am J Clin Nutr 2005;82:281–95.
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.
Alzheimer disease. Arch Neurol 2003;60:940–6.
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.
51 Cheruku SR, Montgomery-Downs HE, Farkas SL, Thoman EB, Lammi-
Gestational age in relation to marine n-3 fatty acids in maternal eryth-
Keefe CJ. Higher maternal plasma docosahexaenoic acid during preg-
rocytes: a study of women in the Faroe Islands and Denmark. Am J
nancy is associated with more mature neonatal sleep-state patterning.
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.
other adverse pregnancy outcomes. Obstet Gynecol Surv 2001;56 (5
53 Genuis SJ. Health issues and the environment—an emerging paradigm
37 Branum AM, Schoendorf KC. Changing patterns of low birthweight
for providers of obstetrical and gynecological healthcare. Hum Reprod
and preterm birth in the United States, 1981-98. Paediatr Perinat Epi-
54 Onwude JL, Lilford RJ, Hjartardottir H, Staines A, Tuffnell D. A rando-
38 Olsen SF, Secher NJ. Low consumption of seafood in early pregnancy as
mised double blind placebo controlled trial of fish oil in high risk preg-
a risk factor for preterm delivery: prospective cohort study. BMJ 2002;
nancy. Br J Obstet Gynaecol 1995;102:95–100.
55 Olafsdottir AS, Skuladottir GV, Thorsdottir I, Hauksson A, Thorgeirs-
39 Allen KG, Harris MA. The role of n-3 fatty acids in gestation and par-
dottir H, Steingrimsdottir L. Relationship between high consumption of
turition. Exp Biol Med 2001;226:498–506.
marine fatty acids in early pregnancy and hypertensive disorders in
40 Olafsdottir AS, Magnusardottir AR, Thorgeirsdottir H, Hauksson A,
Skuladottir GV, Steingrimsdottir L. Relationship between dietary intake
56 Wakita Y. Hypertension induced by methyl mercury in rats. Toxicol Appl
of cod liver oil in early pregnancy and birthweight. BJOG 2005;112:
57 Melanson SF, Lewandrowski EL, Flood JG, Lewandrowski KB. Measure-
41 Williams MA, Zingheim RW, King IB, Zebelman AM. Omega-3 fatty
ment of organochlorines in commercial over-the-counter fish oil prep-
acids in maternal erythrocytes and risk of preeclampsia. Epidemiology
arations: implications for dietary and therapeutic recommendations for
omega-3 fatty acids and a review of the literature. Arch Pathol Lab
42 Armitage JA, Pearce AD, Sinclair AJ, Vingrys AJ, Weisinger RS,
Weisinger HS. Increased blood pressure later in life may be associated
58 Genuis SJ, Schwalfenberg G. Time for an oil check: the role of essential
with perinatal n-3 fatty acid deficiency. Lipids 2003;38:459–64.
omega 3 fatty acids in maternal and pediatric health. J Perinatol 2006;
43 Olsen SF, Secher NJ, Tabor A, Weber T, Walker JJ, Gluud C. Randomised
clinical trials of fish oil supplementation in high risk pregnancies. Fish
59 Genuis SK, Genuis SJ. Exploring the continuum: medical information to
Oil Trials In Pregnancy (FOTIP) Team. BJOG 2000;107:382–95.
effective clinical practice: paper 1. The translation of knowledge into
44 Hibbeln JR. Seafood consumption, the DHA content of mothers‘ milk
clinical practice. J Eval Clin Pract 2006;12:49–62.
and prevalence rates of postpartum depression: a cross-national, eco-
60 Smithells RW, Sheppard S, Schorah CJ. Vitamin deficiencies and neural
logical analysis. J Affect Disord 2002;69:15–29.
tube defects. Arch Dis Child 1976;51:944–50.
ª 2008 The Author Journal compilation ª RCOG 2008 BJOG An International Journal of Obstetrics and Gynaecology
Reisediarrhöe für Taucher Wer kennt das nicht? Man freut sich Monate im Voraus auf den heiß ersehnten Tauchurlaub, und dann das: man kommt von der Toilette des Safaribootes gar nicht mehr herunter und muss mit anhören, wie die Kollegen gesund und munter von Walhaien, Mantas und Nacktschnecken erzählen. Was kann man tun gegen diese Nach neueren Studienergebnissen entwickeln 40-60% alle
Upcoming Events COMMUNITY & SOCIAL ENGAGEMENT from 5 November, on Tuesdays 11:30am-3:30pm The Volunteer Desk will be open once again. This service offers Bocconi students, faculty and staff the opportunity to get to know and approach Milanese organizations committed to social issues, dedicating part of their time to concrete activities. The service is managed thanks to a collabor