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he impac o docosahexaenoic acid on ma e nal men al heal h: scoping e iew
El impac o del ácido docosahexaenoico en la salud men al ma e na: e isión sis ema izada
de la li e a u a
Olga Maso 1,2, Julio José Ochoa He e a3, Elena Pa aíso Pueyo1,2, Judi h Roca1,2, Jèssica Mi anda1,2, Ana La edán San ama ía1,2
1Depa men o Nu sing and Physio he apy. Uni e sidad de Lleida. Lleida, Spain. 2Heal h Ca e Resea ch G oup (GRECS). Ins i u o de In es igación Biomédica de Lleida
Fundación D . Pi a é. IRBLleida. Lleida, Spain. 3Ins i u o de Nu ición y Tecnología de los Alimen os José Ma aix Ve dú (INYTA). Depa men o Physiology. Uni e sidad de
G anada. G anada, Spain
Con lic o in e es : he au ho s decla e no con lic o in e es .
Maso O, Ochoa He e a JJ, Pa aíso Pueyo E, Roca J, Mi anda J, La edán San ama ía A. The impac o
docosahexaenoic acid on ma e nal men al heal h: scoping e iew. Nu Hosp 2023;40(4):848-857
DOI: h p://dx.doi.o g/10.20960/nh.04523
Recei ed: 28/01/2023 • Accep ed: 20/03/2023
Co espondence:
Elena Pa aíso Pueyo. Depa men o Nu sing and
Physio he apy. Uni e sidad de Lleida. C/ Mon se a
Roig, 2. 25198 Lleida, Spain
e-mail: [email p o ec ed]
Re isión
Abs ac
Docosahexaenoic acid (DHA) is a polyunsa u a ed essen ial a y acid om he omega-3 se ies ha appea s o be key o pe ina al men al
heal h. Fo his, he aim o his e iew is o e alua e he e ec o DHA on ma e nal men al heal h du ing p egnancy and lac a ion wi h espec o
dep ession and anxie y. The p esen scoping e iew was ca ied ou ollowing he me hodology o A ksey and O’Malley (2005). The selec ion o
s udies was ca ied ou in acco dance wi h PRISMA by means o sys ema ic sea ches in he PubMed, Scopus, PsycINFO and Medline da abases.
The esul s classi ied acco ding o he e ec i eness o DHA. In mos (n = 9) o he 14 s udies inally included, DHA plasma le els wi h o wi hou
o he polyunsa u a ed omega-3 a y acids we e signi ican ly lowe in p egnan women wi h dep essi e and anxie y symp oms. Howe e , no
s udy epo ed a bene icial e ec o DHA on men al heal h du ing he pos pa um pe iod. The majo i y used de ec ion me hod was he Edinbu gh
Pos pa um Dep ession Scale (n = 11). The p e alence o dep essi e symp oms anged be ween 5.9% and 50%. As a conclusion, al hough
mo e esea ch is needed in his a ea, hese explo a o y esul s sugges ha DHA could play an impo an ole in p e en ing he pa hogenesis o
dep ession and anxie y du ing ges a ion.
Keywo ds:
Docosahexaenoic acid.
Dep ession. Anxie y.
P egnancy. Pos pa um.
Re iew.
Resumen
El ácido docosahexaenoico (DHA) es un ácido g aso esencial poliinsa u ado de la se ie omega-3 que pa ece se cla e pa a la salud men al
pe ina al. Po ello, el obje i o de es a e isión es e alua el e ec o del DHA sob e la salud men al ma e na du an e el emba azo y la lac ancia con
espec o a la dep esión y la ansiedad. La p esen e e isión se lle ó a cabo siguiendo la me odología de A ksey y O’Malley (2005). La selección
de es udios se ealizó de acue do con PRISMA median e búsquedas sis emá icas en las bases de da os PubMed, Scopus, PsycINFO y Medline.
Los esul ados se ca aloga on según la e icacia del DHA. En la mayo ía (n = 9) de los 14 es udios inalmen e incluidos, los ni eles plasmá icos
de DHA con o sin o os ácidos g asos omega-3 poliinsa u ados ue on signi ica i amen e más bajos en muje es emba azadas con sín omas de
dep esión y ansiedad. Sin emba go, ningún es udio in o mó un e ec o bene icioso del DHA sob e la salud men al du an e el pe iodo pospa o. El
mé odo de de ección más u ilizado ue la Escala de Dep esión Pospa o de Edimbu go (n = 11). La p e alencia de sín omas dep esi os osciló
en e el 5,9% y el 50%. Como conclusión, aunque se necesi a más in es igación en es e ámbi o, los esul ados explo a o ios pa ecen indica
que el DHA juega un papel impo an e en la p e ención de la pa ogenia de la dep esión y la ansiedad du an e el pe iodo de ges ación.
Palab as cla e:
Ácido docosahexaenoico.
Dep esión. Ansiedad.
Emba azo. Pospa o.
Re isión.
849THE IMPACT OF DOCOSAHEXAENOIC ACID ON MATERNAL MENTAL HEALTH: SCOPING REVIEW
[Nu Hosp 2023;40(4):848-857]
INTRODUCTION
Docosahexaenoic acid (DHA o 22:6n-3) is an omega n-3
polyunsa u a ed a y acid (PUFA). Chemically, i is a ca boxylic
acid like all a y acids (FAs). DHA is conside ed as he mos im-
po an long-chain PUFA o he n-3 amily. Physiologically, he
human body is able o me abolize DHA h ough con e sion in he
o ganism o alpha linolenic acid (ALA), ano he n-3 PUFA. This
con e sion akes place p incipally in he li e and i is anspo ed
as a phospholipid by plasma albumin, almos exclusi ely, o he
b ain and e ina. In cases o p egnancy, adipose issue also ac s
as a empo a y ese e, bu he deg ee o con e sion is educed,
making i di icul o mee ecommended le els o DHA, con-
side ed o be an essen ial p ena al nu ien (1). Fo his eason,
he Eu opean Food Sa e y Au ho i y (EFSA) (2) ecommenda ion
anges om 100 o 200 mg/day.
Fac o s ha can in luence low DHA in ake in p egnan emales
include le el o educa ion, olde age, smoking and insu icien
ish and sea ood consump ion, especially in he second and hi d
imes e s (3). DHA is ound in ish oil and some algae. In u n,
mos DHA in ish and o he complex o ganisms comes om hei
access o pho osyn he ic he e o ophic mic oalgae. Foods ha
con ain i include cold-wa e ish (like salmon, he ing o ancho-
y), una and cod ish oil (1). As i can be di icul o each he ec-
ommended amoun s h ough die a y in ake, he consump ion o
DHA supplemen s wi h o wi hou o he FAs is ad ised. I should
also be no ed ha omega-3 a y acid supplemen s a e well ole -
a ed by p egnan and lac a ing women (4).
In his g oup o women, his n-3 PUFA pa icipa es in di e en
unc ions (5,6). In e ms o men al heal h, signi ican ly lowe le els
o DHA, EPA and o al n-3 PUFAs ha e been ound in adul pa ien s
wi h dep ession, sugges ing ha n-3 PUFAs play a ole in he pa ho-
genesis o his illness (7), pa icipa ing in neu obiological p ocesses
including con ol o se o one gic and dopamine gic unc ion, modu-
la ion o b ain-de i ed neu o ophic ac o in he hippocampus, egu-
la ion o he hypo halamic-pi ui a y-ad enal axis, and wi h e ec s on
neu oin lamma ion (8). In his ega d, Lin e al. (7) a gued he need
o s udies examining he speci ic unc ions o DHA in di e en popu-
la ion g oups wi h dep essi e symp oms. In his con ex , he p esen
s udy ocuses on ma e nal men al heal h.
One possible solu ion o men al heal h issues in such si ua-
ions is he applica ion o p esc ip ion d ugs. Howe e , because
o hei po en ial oxic, e a ogenic o e en le hal e ec s on he
e us, he use o many o hem is no ecommended du ing p eg-
nancy. In addi ion, he physiological changes inhe en o p eg-
nancy and lac a ion condi ion he abso p ion, ans e , exc e ion
and me abolism o an ipsycho ics (9). Fo his eason, nu i ion-
based ea men s ha e been p oposed as an aid o alle ia e and/
o p e en p ena al anxie y and dep ession (10). The e is he e-
o e an e iden need o know he eal e ec o DHA on men al
heal h du ing p egnancy and he pos pa um pe iod.
None heless, despi e he indings o he e e enced s udies,
he ela ionship be ween DHA and i s e ec on men al heal h
in he p ena al s age is no ully clea (7). I can be specula ed
ha di e en ac ions can occu simul aneously. On one hand, by
main aining and inc easing he b ain s uc u es and p ese ing hei
unc ion by in e ac ing wi h phospholipid me abolism and, hence, he
modula ion o signal ansduc ion. On he o he hand, p e en ing o
dec easing he in lamma o y s a us occu ing du ing dep ession (11).
The aim o his scoping e iew is he e o e o e alua e he e ec o
DHA du ing p egnancy and he pos pa um pe iod on ma e nal men-
al heal h in e ms o dep essi e symp oms and anxie y.
MATERIAL AND METHODS
The scoping e iew amewo k adop ed was based on he me h-
odological model o A ksey and O’Malley (12), wi h con ibu ions om
he P e e ed Repo ing I ems o Sys ema ic e iews and Me a-Anal-
yses ex ension o Scoping Re iews (PRISMA-ScR) (13). Following
he model, he me hodological p ocess was di ided in o i e s ages.
IDENTIFYING THE RESEARCH QUESTION
The esea ch ques ion ha was o mula ed was as ollows: wha
a e he e ec s o DHA du ing p egnancy and he pos pa um pe iod
on ma e nal men al heal h in e ms o dep ession and anxie y?
IDENTIFYING RELEVANT STUDIES
Rele an s udies we e iden i ied by sea ching ecen li e a u e
published be ween Feb ua y and Ma ch 2021 in he PubMed, Sco-
pus, PsycINFO and Medline da abases. The ollowing keywo ds we e
used: “Docosahexaenoic Acid”; “Fish Oil”; “Die a y Supplemen s”;
“P egnancy”; “Ma e nal-Fe al Exchange”; “B eas Feeding”; “De-
p ession; “Dep ession, Pos pa um”; “Men al Heal h”; “Beha io al
Symp oms”; “S ess, Psychological”; “A ec i e Symp oms”; “Anxi-
e y”; “Pos na al dep ession”; and “An ena al dep ession”.
A icles included in his scoping e iew me he ollowing
speci ied inclusion c i e ia: a) analy ical s udies (i.e., andomised
con olled ials [RCT], o mainly obse a ional s udies [c oss-
sec ional, coho and case-con ol]); b) e alua ing he e ec o
DHA on men al heal h (dep ession and anxie y) in p egnan and/
o lac a ing women; c) published in English o Spanish; and d)
published be ween Janua y 2010 and Ma ch 2021. The heal h-
ca e le el a which he s udy was ca ied ou was no conside ed
as ele an . S udies which we e ca ied ou on animals o which
ocused only on o he n-3 PIFAs we e excluded.
STUDY SELECTION
S udy selec ion was ca ied ou as desc ibed abo e and ol-
lowing PRISMA (14). Fi s , he sea ch esul s we e impo ed
in o Mendeley (h ps://www.mendeley.com) o pe o m he du-
plica ion check, hus elimina ing 563 a icles. O he emaining
964 s udies which we e subsequen ly analyzed acco ding o
i le and abs ac , 883 we e disca ded based on he inclusion
850 O. Maso e al.
[Nu Hosp 2023;40(4):848-857]
and exclusion c i e ia, while 81 we e ound o be po en ially eligi-
ble a icles. Subsequen ly, he ele ance o each o he abs ac s
was analyzed, elimina ing 46 in his p ocess. Finally, he ull ex
o he emaining 35 a icles was examined and 14 we e chosen
o inal analysis (Fig. 1). The en i e p ocess was eco ded using
an Excel In o ma ion Manage sp eadshee (15).
CHARTING THE DATA
Fou speci ic componen s we e ex ac ed using a s anda dised
o m: a) gene al da a (au ho [s], yea o publica ion and coun-
y); b) me hodological elemen s (s udy design and popula ion); c)
da a o he in e en ion/obse a ion ca ied ou (i.e., dose o DHA,
measu emen o he p esence o dep ession and/o anxie y, e c.);
and d) da a e alua ing he e ec o DHA on he men al heal h o
p egnan and/o lac a ing women.
COLLATING, SUMMARIZING AND REPORTING
THE RESULTS
The esul s we e classi ied acco ding o whe he o no aking
DHA du ing p egnancy was e ec i e o ma e nal men al heal h.
O he 14 pape s, nine epo ed bene icial e ec s and i e, no
bene icial bene i s.
RESULTS
The esul s a e se ou in h ee di e en sec ions: cha ac e is-
ics o he included s udies, s udies which show he e ec i eness
o DHA in e ms o ma e nal men al heal h, and s udies which
show no such e ec i eness.
CHARACTERISTICS OF INCLUDED STUDIES
The 14 pape s came om a o al o 11 coun ies: wo om
B azil, Uni ed S a es and Japan; and one each om Aus alia,
The Ne he lands, I an, Kenya, Mexico, No way, Uni ed Kingdom
and Taiwan. Exac ly hal o he pape s we e published be ween
2016 and 2018 (n = 7). As o he ype o s udy, six we e RCT,
ou we e p ospec i e coho s, h ee we e c oss-sec ional s ud-
ies and one, a longi udinal case-con ol s udy. These and o he
cha ac e is ics o he s udies a e shown in able I.
Figu e 1.
PRISMA cha . DHA: docosahexaenoic acid; n-3 PUFA: omega-3 polyunsa u a ed a y acids.
Iden i icac ion
Numbe o in e en on s udies
supplemen a ion du ing
p egnancy o –n-3 PuFA–
(n = 6)
Numbe o obse a ional s udies
–n-3 PuFA concen a ions in
ma e nal blood–
(n = 8)
Reco ds excluded
(n = 46)
Full- ex a icles excluded, wi h
easons (n = 21):
• Made in animals (n = 5)
• i is no an o iginal s udy (n = 5)
• Does no s udy he e ec o DHA
in p egnan o lac a ing women
(n = 4)
• Dep essi e symp oma ology o
anxie y is no examined (n = 7)
Sc eening and eligibili yIncluded
Reco ds iden i ied h ough
da abase sea ching
(n = 1527)
Reco ds a e duplica es emo ed
(n = 964)
Reco ds sc eened
(n = 81)
Full- ex a icles assessed o
eligibili y
(n = 35)
s udies included in quali a i e
syn hesis
(n = 14)
851THE IMPACT OF DOCOSAHEXAENOIC ACID ON MATERNAL MENTAL HEALTH: SCOPING REVIEW
[Nu Hosp 2023;40(4):848-857]
Table I. O e iew o included s udies
Au ho (s),
yea o
publica ion
Coun y S udy
design Popula ion In e en ion/obse a ion DHA e ec
S udies whe e DHA was ound o be bene icial o ma e nal men al heal h
Ál a ez-Ramí ez
e al. (16), 2018
Mexico C oss-
sec ional s udy
n = 151 p egnan in second
semes e
DHA in ake: ood equency ques ionnai e
Anxie y: STAI; dep ession: EPDS (≥ 12 poin s)
A e age daily in ake o DHA: 70 mg/day
Anxie y: 44.4%; dep ession: 17.9%
Anxie y: ↑ STAI sco e wi h ↓ DHA in ake (p = 0.03)
Dep ession: ↑ EPDS sco e wi h ↓ DHA in ake
(p = 0.01)
Chang e al. (19),
2018
Taiwan C oss-
sec ional s udy
n = 17 wi h dep ession (DSM-IV)
n = 16 wi hou dep ession (CG)
All we e in he 2nd o 3 d imes e
DHA and o he FAs in blood
Pe ina al dep ession: DSM-IV and EPDS (in medians)
EPDS: 14.6 poin s (SD: ± 3.6) in he g oup wi h
dep ession and 5.3 (SD: ± 3.8) in CG
< DHA le els in he dep essed g oup (p = 0.02)
Fa shba -Khalili
e al. (22), 2016
I an RCT IG: n = 75
CG: n = 75
P egnan
IG: 1,000 mg/day o ish oil supplemen s (wi h 120 mg
o DHA; 180 mg o EPA and 400 mg o ALA)
CG: 1,000 mg/day placebo
Follow-up: beginning (WG 16-20), WG 26-30, WG 35-
37, and 30-45 days pos pa um
Dep ession: EPDS (in medians); se um le els DHA and
EPA
A e ollow-up, signi ican di e ences be ween g oups
we e in mean EPDS sco e (adjus ed mean di e ence
= -1.4 [95% CI: -2.6 o -0.25])
IG: ↓ mean dep ession sco e du ing p egnancy
and he pos pa um pe iod (p < 0.05)
Pin o e al. (17),
2016
B azil Coho s,
p ospec i e
n = 172 p egnan DHA and o he FAs in blood; dep ession: EPDS (≥ 11
poin s)
Follow-up be ween 5-13, 20-26 and 30-36 WG
Dep ession: 1s imes e = 33.7%; 2nd = 18.9%; and
3 d = 17.4%
Ad ancemen o p egnancy = > high concen a ions o
DHA (OR = 0.96, 95% CI 0.93-0.99) and o he FA and
↓ in dep essi e symp oms (p < 0.05)
Shi aishi e al.
(18), 2015
Japan C oss-
sec ional s udy
n = 329 p egnan (WG 19-23) Plasma concen a ions o DHA (48.6-152.4 μg/ml) and
EPA (11.6-107.2 μg/ml); die a y his o y: BDHQ du ing
he mon h p io o he s udy
Dep ession: EPDS (> 8 poin s)
Dep ession: 5.9%
↑ EPDS sco e wi h ↓ DHA in ake (p = 0.09) and ↓
plasma DHA concen a ion (p = 0.04)
Judge e al. (23),
2014
USA RCT (pilo
s udy)
IG: n = 20 p egnan
CG: n = 22 p egnan
IG: DHA (300 mg o DHA)
CG: placebo (wi hou DHA, co n oil capsule)
Consump ion o capsules om 24 o 40 WG (1 capsule
5 days/week)
Dep ession du ing p egnancy: CES-D; pos pa um (up
o 6 mon hs): PDSS (in means)
CES-D: means IG 12.6 (SD: ± 8.3) and CG 9.5
(SD: ± 8.3)
PDSS: means be ween 46.03 and 47.65
↓ o al PDSS sco es in IG: wi h less anxie y/insecu i y
(p = 0.03), emo ional labili y (p = 0.04) and loss o sel
(p = 0.02)
(Con inues on nex page)
852 O. Maso e al.
[Nu Hosp 2023;40(4):848-857]
Table I (Con .). O e iew o included s udies
Au ho (s),
yea o
publica ion
Coun y S udy
design Popula ion In e en ion/obse a ion DHA e ec
S udies whe e DHA was ound o be bene icial o ma e nal men al heal h
Sallis e al. (29),
2014
UK Coho s,
p ospec i e
n = 306 wi h pe ina al
dep ession
n = 2,357 wi hou dep essi e
symp oms
DHA and EPA: changes in hei p esence in
e y h ocy es (1% in DHA and 0.1% in EPA)
Pe ina al, an ena al and pos na al dep ession: EPDS (≥
12 poin s)
Pe ina al dep ession: 11.5%
Posi i e associa ion o EPA (OR = 1.07, 95% CI: 0.99-
1.15) and DHA (OR = 1.08, 95% CI: 0.98-1.19) wi h
pe ina al dep ession
The e we e no associa ions wi h he o he ypes o
dep ession
Ma khus e al.
(21), 2013
No way Coho s,
p ospec i e
n = 35 women who comple ed
he ollow-up
FA in e y h ocy es (28 WG)
Dep ession: EPDS (≥ 10 poin s) measu ed a 3 mon hs
pos pa um
Dep ession: 6.9%
Signi ican associa ion be ween low le els o DHA wi h
highe dep ession sco es (p = 0.006)
Mozu kewich e
al. (24), 2013
USA RCT IG1: n = 39
IG2: n = 38
CG: n = 41
All p egnan a he beginning o
p egnancy had isk o dep ession
IG1: EPA (1,060 mg EPA + 274 mg DHA)
IG2: DHA (900 mg o DHA + 180 mg o EPA)
CG: placebo (soybean oil)
Dep ession: Beck Dep ession In en o y + Mini
In e na ional Neu opsychia ic In e iew a he ime
o en olmen , 26-28 WG, 34-36 WG, and 6-8 weeks
pos pa um
Se um AF: on admission and be ween 34 and 36 WG
↑ DHA (IG2) concen a ions a 34-36 WG, ↓ BDI
sco es (p < 0.05)
IG1 and CG we e no signi ican
S udies ha do no demons a e he e ec i eness o DHA on ma e nal men al heal h
U ech e al. (26),
2020
The
Ne he lands
Case-con ols,
longi udinal
n = 9 wi h majo dep ession
n = 10 wi h anxie y
n = 8 wi h mixed anxie y-
dep ession diso de
CG: 40 heal hy p egnan
DHA and o he FAs in ma e nal e y h ocy es and b eas
milk
Dep ession: EPDS (in means)
P ena al anxie y: DSM-IV
Mean sco es ↑ in g oups wi h majo dep ession (9.5
± 6.1), in mixed diso de (7.6 ± 7.6), and wi h anxie y
(5.1 ± 1.8) han in heal hy (3.0 ± 3.8)
No signi ican associa ions we e ound be ween
p ena al dep ession and/o anxie y and DHA in milk o
ma e nal e y h ocy es
Opiyo e al. (29),
2018
Kenya RCT IG: n = 109
CG: n = 107
All HIV-posi i e p egnan women
IG: daily dose o ish oil ich in n-3 (EPA = 2.15 g; DHA
= 1.02 g)
CG: daily dose o soybean oil (SFA: 0.178 g, MUFA:
0.299 g, PUFA: 0.985 g, wi h aces o EPA: 0.115 g)
Follow-up: 8 weeks be ween WG 14 and 27
Dep ession: Beck’s Dep ession In en o y (< 14)
Mild dep ession: 95.3% in he IG and 97.9% in he
CG
The e we e no signi ican di e ences be ween he wo
g oups in he educ ion o symp oms o dep ession in
HIV-posi i e p egnan women
(Con inues on nex page)
853THE IMPACT OF DOCOSAHEXAENOIC ACID ON MATERNAL MENTAL HEALTH: SCOPING REVIEW
[Nu Hosp 2023;40(4):848-857]
Table I (Con .). O e iew o included s udies
Au ho (s),
yea o
publica ion
Coun y S udy
design Popula ion In e en ion/obse a ion DHA e ec
S udies ha do no demons a e he e ec i eness o DHA on ma e nal men al heal h
Dos San os Vaz e
al. (30), 2017
B azil RCT IG: n = 32
CG: n = 28
All p egnan a isk o dep ession
GI: 1.8 g (1.08 g EPA and 0.72 g DHA)
CG: placebo
Supplemen a ion began a 22-24 WG (T1) and las ed
16 weeks
Dep ession: EPDS (≥ 11 poin s) a 5-13 WG (T0),
22-24 WG (T1), 30-32 WG (T2) and 4-6 weeks
pos pa um (T3)
Dep ession in IG: 50% (T0), 25% (T1), 28.6% (T2)
and 25% (T3)
Dep ession in CG: 46.9% (T0), 37.5% (T1), 34.4%
(T2) and 25% (T3)
The e we e no di e ences be ween IG and CG in
he p e alence o dep ession om p egnancy o
pos pa um
IG women wi h dep ession had a g ea e educ ion
in EPDS om he second o he hi d imes e (p =
0.029)
Kobayashi e al.
(27), 2017
Japan Coho s,
p ospec i e
n = 967 pue pe al women (1
mon h a e deli e y)
n = 710 women (6 mon hs a e
deli e y)
DHA consump ion du ing 26-40 WG: sFFQ
Dep ession: EPDS (≥ 9 poin s)
Dep ession: 19.8% and 12.8% in he pue pe ium
No signi ican associa ions we e obse ed be ween
EPA, DHA, and n-3 PUFA in ake a he end o
p egnancy and pos pa um dep ession a bo h one
mon h and six mon hs o ollow-up
Mak ides e al.
(28), 2010
Aus alia RCT GI: n = 1,197 women
CG: n = 1,202 women
n = 694 newbo ns
GI: ish oil capsules wi h DHA (800 mg/day)
CG: ege able oil capsules wi hou DHA
Bo h om he beginning o he s udy un il bi h
Pos pa um dep ession: EPDS (> 12 poin s); cogni i e
and language de elopmen o he baby: Bayley scale
Pos pa um dep ession: in IG 9.7% and in CG 11.2%
IG compa ed o CG did no gi e lowe le els o
pos pa um dep ession no did i imp o e cogni i e and
language de elopmen in ea ly childhood
DSM-IV: Diagnos ic and S a is ical Manual, 4 h edi ion; IG: in e en ion g oup; CG: con ol g oup; WG: ges a ion week; DHA: docosahexaenoic acid; EPA: eicosapen aenoic acid; STAI: S a e-T ai Anxie y In en o y (Spanish e sion);
EPDS: Edinbu gh Pos pa um Dep ession Scale; FA: a y acids; ALA: alpha-linolenic acid; BDHQ: sel -adminis e ed die his o y ques ionnai e; CES-D: Cen e o Epidemiologic S udies Dep ession Scale; PDSS: Pos pa um
Dep ession Sc eening Scale; HIV: human immunode iciency i us; n-3: omega-3; SFA: sa u a ed a y acids; MUFA: monounsa u a ed a y acids; PUFA: polyunsa u a ed a y acids; sFFQ: semi-quan i a i e ood equency
ques ionnai e; n-3 PUFA: omega-3 polyunsa u a ed a y acids.
854 O. Maso e al.
[Nu Hosp 2023;40(4):848-857]
STUDIES THAT REPORT EFFECTIVENESS
OF DHA WITH RESPECT TO MATERNAL
MENTAL HEALTH
O he 14 analyzed pape s, nine ound ha he consump ion o
ei he DHA alone o in combina ion wi h o he FAs du ing p eg-
nancy was bene icial o ma e nal men al heal h. O hese, six
(16-21) measu ed plasma le els in he mo he while only h ee
(22-24) s udied die a y supplemen s du ing he p egnancy.
Wi h espec o he consump ion o DHA alone, wi hou o he
FAs, his was only pe o med by Judge e al. (23). Signi ican ly
lowe sco es (p = 0.016) we e eco ded on he Pos pa um De-
p ession Sc eening Scale in he IG (46.03 ± 2.17) compa ed o
he con ol g oup (CG) (52.11 ± 2.4).
The e ec o he combina ion o DHA wi h o he FAs has also
been s udied. Daily in ake o DHA a ied be ween 70 mg/day
and 325 mg/day and he p e alence o dep essi e symp oms
be ween 5.8% and 33.7% (16-18,21). Pin o e al. (17) epo ed
a 5% dec ease in he p obabili y o ha ing dep essi e symp oms
o each one-week inc ease in he p egnancy. In all (16-18,21),
i was ound ha p egnan women wi h lowe die a y in ake and
blood concen a ions o DHA had highe sco es on he Edinbu gh
Pos pa um Dep ession Scale (EPDS) (p < 0.05). Likewise, lowe
plasma concen a ions o o he FAs, such as EPA (16-18,21),
docosapen aenoic acid (DPA) (17,21), o al n-3 (17,21), he n-
3/n-6 a io and highly unsa u a ed a (21) we e co ela ed wi h
highe sco es on he EPDS. Finally, i should be no ed ha no
s a is ically signi ican esul s we e ob ained o he pos pa um
pe iod (20,21). As o anxie y, Ál a ez-Ramí ez e al. (16) epo -
ed a p e alence o 44.4% (STAI > 40 poin s) and an inc ease in
he STAI sco e o p egnan women wi h a lowe in ake o DHA
and EPA (p = 0.03).
Two obse a ional s udies ca ied ou a ollow-up o a g oup o
p egnan emales diagnosed wi h pe ina al dep ession (IG) and
ano he wi h no p io pa hology (CG). In he i s o hese, Chang
e al. (19) ound ha he IG had signi ican ly lowe le els o DHA
(p = 0.020), o al n-3 (p = 0.026), and EPA (p = 0.019). In he
second s udy (20), an 11.5% p e alence o pe ina al dep ession
was ound, along wi h a posi i e associa ion be ween DHA and
EPA, and pe ina al dep ession. Howe e , as in he p e ious cases,
no s a is ically signi ican co ela ions we e ound be ween DHA
and EPA plasma concen a ions and pos na al dep ession.
The inal wo pape s ha epo ed a bene icial e ec o DHA
we e RCTs. In he i s o hese (22), a e he ollow-up i was
ound ha ish oil supplemen s signi ican ly educed he mean
EPDS sco e du ing p egnancy (p < 0.05). In he second s udy,
Mozu kewich e al. (24) used wo IGs and a CG (wi h soybean oil).
EPA- ich ish oil was adminis e ed o he i s IG and DHA- ich
ish oil o he second. A he hi d o ou isi s (a 24-36 weeks’
ges a ion), he Beck Dep ession In en o y (BDI) sco e was signi i-
can ly p edic ed by se um DHA (p < 0.05), BDI a en ollmen (p
< 0.001) and admission o ha ing s opped aking he capsules
(p < 0.01). None o he h ee die a y supplemen s signi ican ly
p edic ed he BDI sco es a 6-8 weeks pos pa um.
STUDIES THAT REPORTED NO
EFFECTIVENESS OF DHA WITH RESPECT
TO MATERNAL MENTAL HEALTH
In his sec ion, a desc ip ion is o e ed o he i e s udies which
epo ed no bene icial e ec o DHA on ma e nal men al heal h. In
he obse a ional s udies, an analysis was unde aken o he con-
cen a ion o n-3 PUFAs in blood samples. In he mos ecen o he
s udies, ca ied ou by U ech e al. (26), a longi udinal ollow-up was
made o ou g oups o p egnan women. Mean sco es inc eased
mo e in he g oups wi h a men al diso de han in he heal hy g oup
(CG). Mo eo e , women wi h a majo dep ession diso de did p es-
en lowe le els o n-3 (p = 0.018) and EPA (p = 0.006), and hose
diagnosed wi h a mixed anxie y-dep ession diso de had lowe le -
els o EPA (p = 0.015) and highe le els o DPA (p = 0.001). No
s a is ically signi ican associa ion was ound be ween he anxie y
diso de g oup and any FA. In addi ion, no FA was signi ican ly asso-
cia ed wi h pos pa um dep ession. In he o he obse a ional s udy
(27), a o al o 967 women we e sc eened o pos pa um dep es-
sion. Dep ession was eco ded in 19.8% o he women one mon h
a e deli e y, a alue which ell o 12.8% a six mon hs. No signi i-
can associa ions we e obse ed be ween pos pa um dep ession
and in akes o DHA, EPA and n-3 PUFA.
Jus one s udy, ha o Mak ides e al. (28), adminis e ed only
DHA supplemen s (800 mg/day) o an IG. No signi ican di e -
ences we e ound be ween he pe cen age o women who e-
po ed dep essi e symp oms du ing he i s six mon hs pos -
pa um in he IG and CG (9.67% agains 11.19%; adjus ed
OR 0.85; 95% CI: 0.70-1.02; p = 0.09). Dep essi e symp oms
we e commone among women wi h a p io o cu en diagnosis
o dep ession a en olmen .
The wo RCTs in which DHA was s udied in combina ion wi h
o he FAs we e published by Opiyo e al. (29) and Dos San os
Vaz e al. (30). In he i s o hese (29), all pa icipan s we e
HIV-posi i e p egnan women. A he end o he ollow-up, mos
o he pa icipan s had mild dep essi e symp oms (95.3% in
he IG and 97.9% in he CG), wi h he di e ence no being s a-
is ically signi ican . Finally, in he s udy by Dos San os Vaz e al.
(30), dep ession was de ec ed using he EPDS (≥ 11 poin s) in
di e en ges a ion weeks. A weeks 30-32 o ges a ion, he IG
had highe se um concen a ions o EPA, DHA and lowe n-6/n-3
a io compa ed o he CG. Howe e , he e we e no di e ences
be ween he IG and CG in he p e alence o EPDS sco es o e
ime. Only women in he IG wi h a p e ious his o y o dep ession
had a highe educ ion in he EPDS sco e be ween he second
and hi d imes e compa ed o he CG (p = 0.038). In hei
conclusions, he au ho s a gued ha a daily die a y supplemen
o 1.8 g o n-3 PUFAs du ing 16 weeks had no e ec in e ms o
p e en ing ma e nal dep essi e symp oms.
DISCUSSION
The esul s we e classi ied acco ding o whe he he s udies
showed bene icial e ec s o o he wise o he in ake o DHA du -
855THE IMPACT OF DOCOSAHEXAENOIC ACID ON MATERNAL MENTAL HEALTH: SCOPING REVIEW
[Nu Hosp 2023;40(4):848-857]
ing p egnancy on ma e nal men al heal h in e ms o dep essi e
symp oms and anxie y. The obse a ional ones almos all show
ha he DHA has an impo an e ec in ela ion o ma e nal men-
al heal h (6 yes, 2 no). On he o he hand, he expe imen al ones
do no show ha e ec so clea (3 yes, 3 no). This lowe e ec
in he expe imen al ones may be due o a ious causes (i.e., he
di e en doses, he sample size and e en he di e en coun ies
in which he s udies ha e been pe o med, since i is known ha
he e a e clea di e ences in die s [31]).
Acco ding o he analysis o he pape s ha has been unde -
aken, dose is one o he condi ioning ac o s ha may a ec
he e ec i eness o DHA. Di e en doses we e adminis e ed in
he RCTs (22-24) (Table I). These doses mee he ecommended
daily DHA in ake o he EFSA (2) (a ange om 100 o 200 mg/
day). I should also be no ed ha he e ec i eness o DHA e-
po ed in hese s udies may be a ec ed by he exclusion c i e ia
o a p io his o y o dep ession, anxie y o ce ain o he illnesses.
In o he RCTs wi h highe doses o DHA, no bene icial e ec on
men al heal h was epo ed, hough his may be due o how he
s udies we e de eloped. In he case o Dos San os Vaz e al. (30),
he inclusion c i e ia we e a p io his o y o isk o dep ession. Like-
wise, in he s udy o HIV-posi i e p egnan women (29), he illness
i sel could imply a bias in he esul s gi en he di e en physiologi-
cal and psychological condi ioning ac o s o his g oup o women.
Finally, i should be no ed ha in he s udy by Mak ides e al. (28),
a die a y DHA supplemen o 800 mg/day was ound o be ine ec-
i e in he p e en ion o educ ion o dep essi e symp oms. How-
e e , as limi a ions o hei s udy, he au ho s epo ed ha hey
did no e i y he clinical diagnosis o dep ession be o e he s a
o he RCT. In addi ion, hey associa ed he lowe han expec ed
a e o dep essi e symp oms in he CG o he so-called Haw ho ne
e ec (33), acco ding o which he me e ac o pa icipa ion in a
ial wi h a high deg ee o con ac wi h esea che s helps o p e-
en such symp oms. Finally, in ela ion o he non-e ec i eness o
DHA in p egnan women wi h an es ablished diagnosis o p ena al
dep ession, a ecen s udy by Mezquida e al. (34) epo ed he
associa ion o a speci ic pa e n o obs e ic complica ions wi h a
mo e se e e clinical symp omology like dep ession. All o his may
be in luen ial in e ms o he esul s o he non-e ec i eness o
DHA in his popula ion wi h a his o y o men al illness.
On he o he hand, Mak ides e al. (28) only analyzed he e ec
o DHA in he pos pa um pe iod, while he e ec i eness o DHA
was only ound o be s a is ically signi ican in o he s udies du ing
p egnancy (16-24). In his ega d, a o al o i e s udies (24,26-29)
ound, a e analyzing he e ec o DHA in he pos pa um pe iod, no
posi i e e ec in e ms o he p e en ion o educ ion o dep essi e
o anxie y symp oms. This may be because he die a y supplemen s
we e adminis e ed du ing p egnancy and, he e o e, he concen a-
ions o DHA would ha e lowe ed conside ably in he pos pa um
pe iod. Howe e , he impo ance o DHA o ma e nal men al heal h
in he hi d imes e has been shown. This appea s o be a c i i-
cal pe iod o ensu e adequa e le els o ma e nal DHA o acili a e
op imal cogni i e de elopmen a he end o in ancy (35). In his
ega d, he po en ial e ec s o DHA du ing in ancy and adul hood
a e becoming mo e widely ecognized, sugges ing a he same ime
ha DHA le els can play a ole in cogni i e decline and in ela ion
o he main psychia ic diso de s (36). The e ec may be ela ed o
he in ake o DHA supplemen s inc easing he concen a ions o
17-hyd oxy-docosahexaenoic acid in ma e nal and umbilical co d
blood (p = 0.02) (37).
Finally, ano he condi ioning ac o ha may ha e a ec ed he
esul s is he way dep essi e symp oms we e measu ed. One o
he scales used, in he s udy by Judge e al. (23), was he Cen e
o Epidemiologic S udies Dep ession scale (CES-D) (38). In he
s udy, a C onbach’s α coe icien o 0.89 in he IG and 0.90 in
he CG was epo ed. A no ewo hy esul i compa ed wi h he
o iginal coe icien s o 0.85 and 0.9, espec i ely (38). Fo his
eason, Judge e al. (23) concluded ha he ma e nal CES-D
sco e du ing p egnancy was a signi ican p edic o o pos pa -
um dep essi e symp oms. This inding also suppo s p e ious
esea ch ha iden i ied psychological dis u bance du ing he
p ena al pe iod as a signi ican p edic o o pos pa um dep es-
sion (39,40). Howe e , his scale was no used in he o he s ud-
ies, whe e he mos commonly used scale was he EPDS (25)
(n = 11). This scale measu es dep ession and he emo ional eel-
ings o mo he s in he las weeks o ges a ion. The p e alence
o dep ession anged be ween 5.9% and 50% (16-22,24,26-
28,30). The EPDS has been used wi h di e en cu -o alues
(≥ 12 poin s, ≥ 11, ≥ 10, ≥ 9 and > 8) o simply he mean alues.
Al hough a high EPDS sco e (25) canno con i m a diagnosis o
dep ession, i is conside ed ha a sco e highe han 12 may
indica e a p obable dep essi e diso de (28). A sco e o 10 o 12
ep esen s a c osso e poin and a sco e o 0 o 9, he absence
o pos pa um dep ession (41). In con as , Ma khus e al. (21)
a gue ha he cu -o alue should be ≥ 10, as his is he alue
commonly used in P ima y Ca e se ings.
LIMITATIONS
The selec ed s udies we e ca ied ou in di e en coun ies
wi h la ge sociocul u al and die a y di e ences, making gene al-
iza ions di icul . In addi ion, he e a e impo an gaps in he body
o knowledge wi h espec o he in luence o o he nu ien de i-
ciencies (i.e., gene ic polymo phisms ha a ec he syn hesis o
n-3 FAs and he o al in ake o FAs) o he eal in luence o o he
n-3 FAs (i.e., EPA) in ma e nal men al heal h. Da a on die a y
in ake o a s and measu es o a y acid s a us in blood a e no
collec ed o , a leas , no speci ied in mos pape s.
The s udies a e also limi ed in many ins ances by a small sam-
ple numbe o he inclusion/exclusion c i e ia ha we e used in
ela ion o men al heal h issues p io o p egnancy. Fo he abo e
easons, he esul s o hese s udies canno be conside ed o be
conclusi e.
CONCLUSIONS
This scoping e iew ocuses on iden i ying he e ec i eness
o DHA wi h espec o ma e nal men al heal h. In mos o he
856 O. Maso e al.
[Nu Hosp 2023;40(4):848-857]
s udies analyzed (n = 9), highe se um concen a ions o his
n-3 PUFA, whe he due o a high na u al in ake o die a y sup-
plemen s, we e shown o in luence educing he p e alence o
dep essi e and anxie y symp oms. Al hough mo e esea ch is
needed, hese explo a o y esul s he e o e seem o indica e ha
DHA plays an impo an ole in he p e en ion o he pa hogen-
esis o hese wo men al illnesses du ing he ges a ion pe iod.
Howe e , i appea s o lose e ec i eness in he pos pa um
pe iod, since no s udies analyzed in his e iew had shown an
e ec o DHA on dep essi e o anxie y symp oms. The indings
lend suppo o he hypo hesis o he implica ion o phospholipids
in dep ession. Howe e , u he esea ch in his a ea is equi ed.
Fu u e in es iga ions should aim o eplica e indings in la ge
da a se s and cla i y possible pa hophysiological mechanisms.
Ano he esea ch line would be o in es iga e wha happens wi h
mul iple p egnancies gi en ha all he s udies made o da e ha e
concen a ed on single on p egnancies. I should also be no ed
ha e y ew o he pape s ha e conside ed only he use o DHA,
wi h mos s udying DHA in combina ion wi h o he PUFAs like
EPA. Fu he esea ch is he e o e equi ed o know he indi idual
e ec o DHA on ma e nal men al heal h.
Finally, di e en scales we e used o de ec dep essi e symp-
oms, wi h he EPDS being he mos equen ly employed. How-
e e , he e appea s o be no consensus on he cu -o alue.
Cla i ying his ques ion is key in e ms o he heal hca e impli-
ca ions o he sys ema ic de ec ion o dep ession du ing p eg-
nancy and he pos na al pe iod and, in his way, ensu ing ea ly
in e en ion and he co ec ackling o he diso de .
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