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The impact of docosahexaenoic acid on maternal mental health: scoping review

Masot, Olga,Ochoa Herrera, Julio José

Abstract

Introduction: Docosahexaenoic acid (DHA) is a polyunsaturated essential fatty acid from the omega-3 series that appears to be key to perinatal mental health. For this, the aim of this review is to evaluate the effect of DHA on maternal mental health during pregnancy and lactation with respect to depression and anxiety. The present scoping review was carried out following the methodology of Arksey and O'Malley (2005). The selection of studies was carried out in accordance with PRISMA by means of systematic searches in the PubMed, Scopus, PsycINFO and Medline databases. The results classified according to the effectiveness of DHA. In most (n = 9) of the 14 studies finally included, DHA plasma levels with or without other polyunsaturated omega-3 fatty acids were significantly lower in pregnant women with depressive and anxiety symptoms. However, no study reported a beneficial effect of DHA on mental health during the postpartum period. The majority used detection method was the Edinburgh Postpartum Depression Scale (n = 11). The prevalence of depressive symptoms ranged between 5.9 % and 50 %. As a conclusion, although more research is needed in this area, these exploratory results suggest that DHA could play an important role in preventing the pathogenesis of depression and anxiety during gestation.

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Nu ición Hospi ala ia ISSN (elec ónico): 1699-5198 - ISSN (papel): 0212-1611 - CODEN NUHOEQ S.V.R. 318 ©Copy igh 2023 SENPE y ©A án Ediciones S.L. Es e es un a ículo Open Access bajo la licencia CC BY-NC-SA (h p://c ea i ecommons.o g/licenses/by-nc-sa/4.0/). 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 . REFERENCES 1. Innis SM. Pe ina al biochemis y and physiology o long-chain polyun- sa u a ed a y acids. J Pedia 2003;143(4):1-8. DOI: 10.1067/S0022- 3476(03)00396-2 2. 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