Maternal supplementation with small-quantity lipid-based nutrient supplements during pregnancy and lactation does not reduce depressive symptoms at 6 months postpartum in Ghanaian women: a randomized controlled trial

ORIGINAL ARTICLE Ma e nal supplemen a ion wi h small-quan i y lipid-based nu ien supplemen s du ing p egnancy and lac a ion does no educe dep essi e symp oms a 6 mon hs pos pa um in Ghanaian women: a andomized con olled ial Ha ie Ok onipa 1,2 &Se h Adu-A a wuah 2 &Anna La ey 2 &Pe Asho n 3 & S ephen A. Vos i 4 &Rebecca R. Young 1 &Ka h yn G. Dewey 1 Recei ed: 2 Ap il 2017 /Accep ed: 19 June 2017 /Published online: 11 July 2017 #The Au ho (s) 2017. This a icle is an open access publica ion Abs ac We examined he impac on dep ession a 6 mon hs pos pa um o ma e nal supplemen a ion wi h small-quan i y lipid-based nu ien supplemen (SQ-LNS) compa ed o supplemen a ion wi h i on and olic acid (IFA) o mul iple mic onu ien s (MMN). In his pa ially double-blinded andomized con olled ial, p egnan women ≤20 weeks ges a ion (n= 1320) we e ec ui ed om an ena al clinics and andomly assigned o ecei e ei he (1) SQ-LNS du ing p egnancy and o 6 mon hs pos pa um, o (2) IFA du ing p egnancy only, o (3) MMN du ing p egnancy and o 6 mon hs pos pa um. Ma e nal dep essi e symp oms we e measu ed a 6 mon hs pos pa um using he Edinbu gh Pos na al Dep ession Scale (EPDS). Women who sco ed 12 o mo e on he EPDS we e conside ed o show symp oms o dep ession. One housand one hund ed i y-one women we e included in his analysis (LNS = 382, IFA = 387 and MMN = 382). Cha ac e is ics o he h ee g oups we e simila a baseline, and he e we e no signi ican di e ences be ween women whowe eincludedin heanalysis(n= 1151) and hose who we e no (n= 169). A 6 mon hs pos pa um, 13% o he women o e all showed symp oms o dep ession, and his did no di e by g oup (LNS = 13.1%, IFA = 11.2% and MMN = 14.7%. P= 0.36). The median (25, 75 pe - cen ile) EPDS sco e did no di e by g oup (LNS 4.0 (1.0, 8.0), IFA 4.0 (1.0, 8.0), MMN 5.0 (2.0, 9.0), P ans o med = 0.13). Adjus men o co a ia es did no al e hese indings. Ma e nal supplemen a ion wi h SQ-LNS compa ed o MMN o IFA did no a ec pos na al dep es- si e symp oms in his sample o Ghanaian women. Keywo ds Lipid-based nu ien supplemen s .Pos pa um dep ession .Ghana In oduc ion Globally, pos pa um dep ession (PPD) has been epo ed o a ec 10–20% o women (Fishe e al. 2012; Nhiwa iwa e al. 1998;O’Ha a and Swain 1996; S ewa e al. 2016;Uwakwe 2003). In one s udy in he Eas e n egion o Ghana, 9.3% o he women we e epo ed o show symp oms o dep ession a 6 mon hs pos pa um (Ok onipa e al. 2012). O e he yea s, PPD has ecei ed a en ion because o he dele e ious e ec i may ha e on bo h ma e nal and child heal h. Fo example, se e al s udies ha e epo ed associa ions be ween PPD and inc eased in an dia hoeal episodes (Ok onipa e al. 2012; Rahman e al. 2007), poo mo he -child in e ac ions (Mu ay e al. 1996) and sub-op imal b eas eeding p ac ices (Hende son e al. 2003). Inadequa e nu i ion may play a ole in men al heal h, including dep ession. Links be ween nu ien de iciencies andmoodha ebeen epo ed o ola e, i amin B-12, Clinical ials.go iden i ie : NCT00970866. *Ha ie Ok onipa heok onipa@ucda is.edu 1 P og am in In e na ional and Communi y Nu i ion, Depa men o Nu i ion, Uni e si y o Cali o nia, 3135 Meye Hall, One Shields A enue,Da is,CA95616,USA 2 Depa men o Nu i ion and Food Science, Uni e si y o Ghana, Legon, Acc a, Ghana 3 Cen e o Child Heal h Resea ch, Uni e si y o Tampe e School o Medicine and Tampe e Uni e si y Hospi al, Tampe e, Finland 4 Depa men o Ag icul u al and Resou ce Economics, Uni e si y o Cali o nia, Da is, CA, USA A ch Womens Men Heal h (2018) 21:55–63 DOI 10.1007/s00737-017-0752-7 calcium, i on, selenium, zinc and omega-3 a y acids (Bodna and Wisne 2005; Leung and Kaplan 2009). Resul s o andomized con olled ials ha ha e exam- ined nu ien supplemen a ion and PPD ha e howe e been mixed. In Gua emala, weekly s daily supplemen a- ion wi h mul iple mic onu ien s (MMN) o 12 weeks esul ed in imp o ed dep ession sco es among women o ep oduc i e age (Nguyen e al. 2009). Among Bangladeshi p egnan women, supplemen a ion wi h MMNcompa ed o30mgi on om14weeksges a ion o 12 weeks pos pa um esul ed in lowe dep ession sco es (F i h e al. 2009). In Indonesia, howe e , MMN supplemen a ion om p egnancy o 3 mon hs pos pa um had no signi ican e ec on ma e nal ‘mood’compa ed o p o ision o i on and olic acid (IFA) (P ado e al. 2012). In Sou h A ica, supplemen a ion du ing lac a ion wi h i on (compa ed o placebo) imp o ed dep ession among anaemic bu no among non-anaemic women (Bea d e al. 2005). Omega-3 a y acids a e ano he g oup o nu ien s ha ha e ecei ed a en ion because o hei po en ial ole in he ea men o dep ession. S udies in animals ha e sug- ges ed ha omega-3 a y acids can a ec b ain p ocesses such as hose ha con ol mood and anxie y (Ca lezon e al. 2005; Delion e al. 1996). Howe e , esea ch in humans on he associa ion be ween omega-3 a y acid supplemen a ion and dep ession has yielded inconsis en esul s. A me a-analysis o eigh ials conduc ed in pa- ien s wi h dep essi e symp oms epo ed a signi ican clinical bene i o n-3 a y acid ea men compa ed o placebo (G osso e al. 2014). Howe e , ano he me a- analysis o 12 andomized con olled ials ound li le e idence o suppo he use o omega-3 PUFAs o im- p o e dep essed mood (Apple on e al. 2006). Small-quan i y lipid-based nu ien supplemen s (SQ- LNS) we e designed o en ich he die s o a ge g oups a high isk o malnu i ion (A imond e al. 2013). They a e usually made wi h ege able oil, g oundnu pas e, milk powde , suga and mic onu ien s and p o ide ene gy, mic o- and mac o- nu ien s as well as essen ial a y acids. We conduc ed a ial o examine he e icacy o SQ-LNS p o ided o women du ing p egnancy and he i s 6 mon hs pos - pa um, and o hei o sp ing om 6 o 18 mon hs o age, on p egnancy ou comes and on child g ow h a 18 mon hs. As a seconda y objec i e, we sough o examine he impac o o i ica ion o ma e nal die wi h SQ-LNS compa ed o supplemen a ion wi h IFA and MMN on ma e nal PPD. We hypo hesized ha women who ecei ed SQ-LNS du ing p egnancy would ha e lowe mean Edinbu gh Pos na al Dep ession Scale (EPDS) sco es a 6 mon hs pos pa um compa ed o women who ecei ed ei he IFA o MMN. Me hods S udy si e, design and a ms The In e na ional Lipid-Based Nu ien Supplemen s ial in Ghana (iLiNS-DYAD) was conduc ed om No embe 2009 oMa ch2014in helowe ManyaandYiloK obo dis ic s in he Eas e n egion o Ghana. The a ea is semi- u ban, and is abou 70 km om he na ional capi al, Acc a. De ails o he s udy design ha e been desc ibed elsewhe e (Adu-A a wuah e al. 2015). B ie ly, women we e andomly assigned o ecei e one o he ollowing ea men s: (a) daily i on (60 mg) and olic acid (400 μg) capsule du ing p egnancy, and calcium (Ca) only (akin o a placebo) du ing he i s 6 mon hs pos pa um (IFA g oup); (b) daily mul iple mic onu ien capsule (1–2 RDAs o 18 i amins and mine als including 20 mg i on) du ing p egnancy and he i s 6 mon hs pos pa um (MMN g oup); and (c) daily 20 g SQ-LNS du ing p eg- nancy and he i s 6 mon hs pos pa um (LNS g oup). The20gSQ-LNScon ainedsimila i aminandmine al con en as he MMN capsule, plus ano he ou mine als (Ca, P, K, Mg) and essen ial a y acids (4.59 g linoleic acid, 0.59 g α-linolenic acid), and p o ided 118 kcal en- e gy (Table 1). De ails o how pa icipan s we e andomly assigned o he ea men g oups ha e been desc ibed elsewhe e (Adu-A a wuah e al. 2015,2016). The IFA/ MMNwe ep o idedascapsulesinablis e packwhe eas he SQ-LNS supplemen was in a 20-g sache . In a p e ious pape , we epo ed a empo a y mislabeling o IFA and MMN capsules (Adu-A a wuah e al. 2015,2016). B ie ly, some women (n= 170) who had been ini ially assigned o he IFA g oup ecei ed he MMN capsule ei he h oughou p egnancy (n= 85) o du ing pa o p egnancy (n= 85), be o e ecei ing he in ended IFA capsule he es o ollow-up, and ano he 170 women ini ially assigned o he MMN g oup also ecei ed he IFA capsule ei he h oughou p egnancy (n= 78) o du ing pa o p egnancy (n=92),be- o e ecei ing he in ended MMN capsule. Women in he LNS g oup ecei ed he co ec supplemen h oughou he s udy. In his cu en analysis, we included all o he women en- olled in o he s udy wi hou disca ding any da a om hose who ecei ed he unin ended supplemen s, since he unin end- ed exposu e occu ed only in he p e-na al pe iod. As p e i- ously epo ed, women in he IFA and MMN g oups we e exposed o he unin ended supplemen o only 13% o he ollow-up days (Adu-A a wuah e al. 2016). Ou main analy- sis was based on he supplemen women we e in ended o ecei e when hey we e en olled. In o de o add ess he p o- ocol iola ion associa ed wi h he consump ion o mislabeled capsules by some o he women du ing p egnancy, we con- duc ed wo sensi i i y analyses; he i s examined da a based on he supplemen ha women ac ually ecei ed when hey 56 Ok onipa H. e al. we e en olled, and he second examined da a only o women who ecei ed supplemen s a e he mislabeling o IFA and MMN supplemen s had been co ec ed. Rec ui men and ollow-up A de ailed accoun o he ec ui men p ocess has been gi en elsewhe e (Adu-A a wuah e al. 2015). B ie ly, p egnan women we e ec ui ed om he an ena al clinics o wo hos- pi als, one polyclinic and one heal h cen e in he s udy a ea. Women we e conside ed eligible o he s udy i hey we e (1) p egnan , (2) 18 yea s o olde , (3) 20 ges a ional weeks o less and (4) had an an ena al ca d comple e wi h his o y and ex- amina ion. Women we e excluded om he s udy i hey (1) epo ed milk o peanu alle gy, (2) li ed ou side he s udy a ea, (3) in ended o mo e ou o he s udy a ea wi hin he nex 2 yea s, (4) we e unwilling o ecei e ield wo ke s in hei homes o ake s udy supplemen s, (5) we e pa icipa ing in ano he clinical ial o (6) hei an ena al ca d indica ed ha hey had HIV in ec ion, as hma, epilepsy, ube culosis o any malignancy. Eligible women we e ollowed up h ough 6 mon hs pos pa um. Supplemen s we e deli e ed o women bi-weekly du ing p egnancy and lac a ion, and in o ma ion on supplemen in ake and o he da a we e also collec ed bi-week- ly. The dep ession ques ionnai e was adminis e ed a 6 mon hs pos pa um du ing a scheduled home isi . Ou come a iables Ma e nal epo o dep essi e symp oms was assessed a 6 mon hs pos pa um using he EPDS (Cox e al. 1987). The ques ionnai e was ead aloud o he pa icipan in hei own language, and as much as possible, he in e iew was conduc - ed in p i a e, wi h only he ield wo ke and pa icipan p es- en . The EPDS is a 10-i em scale ha documen s dep essi e symp oms ha occu ed o e he pas 7 days. Each i em was sco ed on a ou -poin a ing scale ha ep esen ed he le el o occu ence (ze o he lowes le el o occu ence, h ee he highes le el o occu ence). The sco es o all 10 i ems we e hen summed up o ob ain a o al dep ession sco e. Women wi h a o al EPDS sco e o 12 and abo e we e classi ied as showing symp oms o PPD whe eas women who sco ed be- low 12 we e classi ied as no showing symp oms o PPD (Chibanda e al. 2010;Law iee al.1998). This ques ionnai e has p e iously been used in Ghana (Ok onipa e al. 2012)and o he A ican coun ies (Nhiwa iwa e al. 1998; S ewa e al. 2016;Uwakwe2003) o measu e symp oms o PPD. O he a iables We collec ed o he da a on ma e nal and household baseline a iables including ma e nal yea s o o mal educa ion, age, body mass index (BMI, kg/m 2 ), ma i al s a us, anaemia, ges a ional age, p imipa i y, household asse index, household ood insecu i y index, housing index and season when dep es- sion da a we e collec ed (we /d y). S a is ical analysis The s a is ical analysis plan was pos ed on ou websi e (www. ilins.o g) be o e any analysis was ini ia ed. The p ima y ou come was ma e nal o al dep ession sco e a 6 mon hs pos pa um. We also examined he p opo ion o women who sco ed ≥12 on he EPDS. All analysis was ca ied ou using SAS o Windows Ve sion 9.4 (SAS Ins i u e, CARY, NC, USA) and was by in en ion o ea . All pa icipan s who had missing da a o he ou come a iable we e excluded om all analysis. Desc ip i e da a a e p esen ed as means and s anda d de ia ions o equencies and pe cen ages. Analysis o a iance and chi-squa ed es ing we e used o compa e baseline a iables be ween he h ee in e en ion g oups. Adhe ence o supplemen in ake du ing p egnancy and lac a- ion was calcula ed as he pe cen age o p egnancy days a e en olmen o deli e y and om deli e y o 6 mon hs pos pa - um, espec i ely, when supplemen s we e epo edly consumed. The di e ence in he dep ession sco es be ween he h ee g oups was analysed using ANCOVA, wi h Tukey adjus men o pai wise compa isons. Due o he non-no mal dis ibu ion o he dep ession sco es, we squa e- oo ans o med he a - iable be o e use in analysis. The p opo ion o women who sco ed ≥12 on he EPDS was compa ed be ween he h ee in e en ion g oups using logis ic eg ession. We calcula ed unadjus ed means (SD) o g oup pe cen ages and hen epea ed he analyses wi h adjus men s o p e- speci ied co a ia es. Co a ia es we examined included ma e - nal yea s o o mal educa ion, heigh , age, BMI, ma i al s a us, anaemia a en olmen , ges a ional age a en olmen , p imipa i y, household asse index, household ood insecu i y index and season when dep ession da a we e collec ed. Only co a ia es signi ican ly associa ed wi h he ou come a 10% le el o signi icance in bi a ia e analysis we e included in he inal adjus ed model. A P alue was conside ed o be signi - ican i α<0.05 (unless o he wise s a ed). We es ima ed pai wise in e en ion g oup di e ences in means and ela i e isk o con inuous and bina y ou comes, espec i ely. As pe ou analysis plan, we examined po en ial in e ac- ions be ween he in e en ion g oup and he a iables ha could modi y he impac o he in e en ion on dep ession ou comes. The p e-speci ied baseline a iables include ma e - nal yea s o o mal educa ion, heigh , age, BMI, ma i al s a us, anaemia a en olmen , ges a ional age a en olmen , p imipa i y, household asse index, household ood insecu i y index and season a dep ession da a collec ion. When an e ec modi ie was s a is ically signi ican (P< 0.1), we pe o med a s a i ied analysis by assessing he adjus ed g oup e ec a Lipid-based nu ien supplemen a ion and pos pa um dep ession 57 di e en le els o he e ec modi ie . Fo a con inuous e ec modi ie , he g oup e ec was compa ed a he en h pe cen- ile, he median and he 90 h pe cen ile o con inuous ou - comes and o a ca ego ical e ec modi ie , he g oup e ec was compa ed o all le els o he e ec modi ie . E hics E hical app o al o he s udy was ob ained om he ins i u- ional e iew boa ds o he Uni e si y o Cali o nia, Da is; Ghana Heal h Se ice and Uni e si y o Ghana Noguchi Memo ial Ins i u e o Medical Resea ch (NMIMR). Resul s Pa icipan s Da a we e collec ed be ween Decembe 2009 and Augus 2012. Ou o 2607 women who we e sc eened a he an ena al isi s, 1926 we e eligible o be ec ui ed. O his numbe , 1575 we e ec ui ed (signed consen o m) and 1320 en olled (pa - icipa ed in baseline assessmen and andomized o one o he h ee s udy g oups) (Fig. 1). O he 1320 en olled, dep ession da a we e a ailable o 87% (LNS = 87%, MMN = 87%, IFA = 88%) and hese women we e included in his analysis. The e we e no s a is ically signi ican di e ences in baseline cha ac e is ics be ween pa icipan s who we e included in his analysis and hose who we e excluded. The baseline cha ac- e is ics o women included in he s udy a e shown in Table 2. On a e age, women we e in hei mid- wen ies, we e abou 159 cm all, had abou 7 yea s o o mal educa ion and had ges a ional age o 16 weeks. Almos all women epo ed being ma ied o cohabi ing wi h a pa ne . The e we e no signi ican di e ences in baseline cha ac e is ics be ween he h ee in e - en ion g oups wi hin his analy ical sample. Repo ed adhe - ence (pe cen age o days supplemen s was epo edly con- sumed) o supplemen in ake in women was lowe in he LNS compa ed o he IFA and MMN g oups du ing p egnan- cy (72.5% ± 21.5 s 77.4% ± 16.9 s 76.7% ± 17.2%, espec- i ely, P< 0.001) and pos pa um (70.0% ± 24.6 s 77.3% ± 19.6 s 74.7% ± 21.6%, espec i ely, P<0.001). As p e iously epo ed (Adu-A a wuah e al. 2015,2016), we ound no signi ican di e ences in epo ed se e e ad e se e en s be ween g oups. Main g oup compa isons Tables 3and 4p esen he unadjus ed and adjus ed esul s o con inuous and bina y ou comes, espec i ely, by he in e - en ion g oup. The epo ed dep ession sco es a 6 mon hs pos pa um did no di e signi ican ly be ween he h ee in- e en ion g oups (Table 3). Simila ly, when we examined he p opo ion o women who sco ed ≥12 on he EPDS, we ound no signi ican di e ences be ween LNS, IFA and MMN g oups (Table 4). Adjus men o co a ia es did no al e hese indings. E ec modi ica ion We examined 11 p e-speci ied po en ial e ec modi ie s, and 3 in e ac ions we e signi ican (P< 0.1): season when dep es- sion da a we e collec ed (P= 0.034), housing index (P= 0.053) and child sex (P= 0.099). Among women in e iewed du ing he d y season, hose in he LNS g oup had lowe EPDS sco es compa ed o hose in he IFA and MMN g oups (1.73 s 1.95 s 2.08, P= 0.015). By con as , he e we e no signi ican di e ences be ween LNS, IFA and MMN g oups among women who we e in e iewed du ing he we season (2.07 s 1.91 s 2.03, P= 0.36). Among wom- en who deli e ed emale in an s, he e was a end o hose in he LNS g oup o ha e lowe EPDS sco es compa ed o hose in he IFA and MMN g oups (1.83 s 2.01 s 2.13, P=0.05), bu he e we e no signi ican di e ences among women who deli e ed male in an s. Among women who had highe (90 h pe cen ile) housing index, hose in he IFA g oup had lowe sco es compa ed o he MMN g oup (P= 0.013) bu no com- pa ed o he LNS g oup; none o he g oup di e ences was signi ican among women who had a lowe housing index. Sensi i i y analysis In o de o add ess he p o ocol iola ion associa ed wi h he consump ion o mislabeled capsules by some o he women du ing p egnancy as desc ibed in he me hods sec ion abo e, we conduc ed wo sensi i i y analyses ha examined da a (1) based on he supplemen ha women ac ually ecei ed when hey we e en olled and (2) only o women who ecei ed supplemen s a e he mislabeling o IFA and MMN supple- men s had been co ec ed. When we examined he da a based on he supplemen ha women ac ually ecei ed when hey we e en olled, we ound ha , o e all, he IFA g oup eco ded he highes dep ession sco e compa ed o LNS and MMN g oups in bo h unadjus ed (2.10 s 1.91 s 1.90, P= 0.039) and adjus ed (2.09 s 1.89 s 1.91, P= 0.032) analysis. In he pai wise compa isons, he IFA g oup ended o epo highe sco es compa ed o he MMN (unadjus ed: P=0.07; adjus ed: P=0.05)andLNS (unadjus ed: P= 0.06; adjus ed: P= 0.07). Dep ession sco es we e no signi ican ly di e en be ween he MMN and LNS g oups in adjus ed and unadjus ed analysis. The p opo ion o women who sco ed ≥12 on he EPDS did no di e signi i- can ly be ween he 3 in e en ion g oups in ei he adjus ed o unadjus ed analysis. In he analysis es ic ed o women who ecei ed supple- men s a e he mislabeling o IFA and MMN supplemen s 58 Ok onipa H. e al. had been co ec ed, we ound no signi ican di e ences be- ween g oups in epo ed dep ession sco es a 6 mon hs pos - pa um in ei he unadjus ed o adjus ed analysis, o in he p opo ion o women who sco ed ≥12 on he EPDS (da a no shown). Discussion In his semi-u ban a ea o Ghana whe e he iLiNS s udy was conduc ed, p o ision o SQ-LNS did no alle ia e dep essi e symp oms a 6 mon hs pos pa um. The indings do no sup- po ou hypo hesis ha women who ecei ed SQ-LNS du ing p egnancy would ha e lowe mean EPDS sco es a 6 mon hs pos pa um compa ed o women who ecei ed ei he IFA o MMN. In e ms o p e alence o PPD, ou esul s a e simila o wha was epo ed in ano he s udy in he same s udy a ea (9.3%) whe e ou s udy was conduc ed (Ok onipa e al. 2012). S udies conduc ed in o he A ican coun ies ha e also epo ed simila a es (11–16%) o PPD (Nhiwa iwa e al. 1998; S ewa e al. 2016;Uwakwe2003). Ou inding o no impac o SQ-LNS supplemen a ion on ma e nal PPD is consis en wi h wha was ound in he iLiNS- Malawi ial (S ewa e al. 2016) which used he same s udy design as ou s udy. I is possible ha he o mula ion o SQ- LNS used in hese ials (which included 0.59 g alpha- linolenic acid (ALA) and 4.59 g linoleic acid) did no con ain enough essen ial a y acids (EFA) o in luence dep ession, o he e was insu icien con e sion o he p e-cu so ALA o he longe chain a y acids eicosapen aenoic acid (EPA) and docosahexaenoic acid (DHA). A ecen me a-analysis o de- p ession ials showed ha EPA/DHA supplemen s con aining much highe doses (>60%) o EPA ( anging om 0.2 o 2.2 g, in excess o DHA) we e mo e e ec i e in ea ing dep ession (Suble e e al. 2011) han supplemen s con aining lowe doses Fig. 1 S udy p o ile. The IFA g oup ecei ed 60 mg i on plus 400 mg olic acid. The MMN g oup ecei ed 1–2 Recommended Die a y Allowances o 18 i amins and mine als (including 20 mg i on). The LNS g oup ecei ed SQ-LNS wi h he same mic onu ien s as he MMN g oup, plus ano he ou mine als (Ca, P, K and Mg), as well as mac onu ien s. All h ee supplemen s we e in ended o daily consump ion. IFA i on and olic acid, SQ-LNS small-quan i y lipid-based nu ien supplemen , MMN mul iple mic onu ien s Lipid-based nu ien supplemen a ion and pos pa um dep ession 59 (<60%) o EPA. Thus, inc easing he ALA dose in u u e SQ- LNS supplemen s o le els highe han we used in ou s udy o including EPA/DHA (wi h highe EPA dose) may be mo e likely o in luence dep ession. Al e na i ely, i is possible ha women in he s udy a ea egula ly consumed ish wi h high EFA con en and so had adequa e EFA s a us a baseline, making i di icul o ob- se e an e ec o SQ-LNS supplemen a ion on dep ession. Da a om he Food and Ag icul u e O ganiza ion balance shee s suppo he possibili y o high ish consump ion in Ghana (Michaelsen e al. 2011). Da a p e iously epo ed om ou s udy also show he EFA s a us o women a baseline o be wi hin no mal le els (Oaks e al. 2017). Addi ionally, i is also possible ha dep essi e symp oms we e no common in ou sample a baseline, be o e supple- men a ion, which would also make i di icul o de ec any e ec o supplemen a ion. We did no collec da a on base- line dep ession s a us, so we canno e alua e his possibil- i y. Las ly, i is possible ha o he causes o dep ession we e mo e in luen ial in ou popula ion han nu i ion- ela ed ac o s. A numbe o non-die a y ac o s including ma i al s a us and ela ionship, social suppo , childca e s ess, in an empe amen , socioeconomic s a us and un- planned p egnancy ha e been epo ed o be s ong p edic- o s o pos pa um dep ession (Beck 2001). Resul s o ou p e-speci ied es s o in e ac ions sug- ges ed ha season when dep ession da a we e collec ed, child sex and housing index modi ied he e ec o he Table 1 Composi ion and o mula ion o supplemen s used in he s udy Nu ien Chemical o m used in supplemen o mula ion IFA MMN SQ-LNS a Ra ion (g/day) 1 able 1 able 20 To al ene gy (kcal) 0 118 P o ein (g) 0 2.6 Fa (g) 010 Linoleic acid (g) 0 4.59 α-Linolenic acid (g) 0 0.59 Vi amin A (μg RE) Re inyl ace a e 800 800 Vi amin C (mg) L-asco bic acid 100 100 Vi amin B 1 (mg) Thiamin hyd ochlo ide 2.8 2.8 Vi amin B 2 (mg) Ribo la in 2.8 2.8 Niacin (mg) Niacinamide 36 36 Folic acid (μg) P e oyl monoglu amic acid 400 400 400 Pan o henic acid (mg) Calcium pan o hena e 7 7 Vi amin B 6 (mg) Py idoxine hyd ochlo ide 3.8 3.8 Vi amin B 12 (μg) Cyanocobalamin (0.1%) 5.2 5.2 Vi amin D (IU) Cholecalci e ol (D3) 400 400 Vi amin E (mg) DL-alpha- ocophe ol ace a e 20 20 Vi amin K (μg) Phylloquinone 5% 45 45 I on (mg) Encapsula ed e ous sulpha e 60 20 20 Zinc (mg) Zinc sulpha e 30 30 Coppe (mg) Encapsula ed coppe sulpha e 4 4 Calcium (mg) T icalcium phospha e 0 280 Phospho us (mg) T icalcium phospha e 0 190 Dipo assium phospha e Po assium (mg) Po assium chlo ide 0 200 Dipo assium phospha e Magnesium (mg) Magnesium ci a e 0 65 Selenium (μg) Sodium seleni e 1.5% 130 130 Iodine (μg) Po assium ioda e 250 250 Manganese (mg) Manganese sulpha e 2.6 2.6 In o ma ion om able p e iously published om Adu-A a wuah e al. (2015) and A imond e al. (2013) IFA i on and olic acid capsule, MMN mul iple mic onu ien supplemen capsule, SQ-LNS small-quan i y lipid- based nu ien supplemen o p egnan and lac a ing women a Nu ien concen a ions include con ibu ions om he ing edien s as well as om he mul iple mic onu ien p emix 60 Ok onipa H. e al. in e en ion. Among women in e iewed du ing he d y season, hose in he LNS g oup had signi ican ly lowe EPDS sco es compa ed o hose in he MMN g oup. I is possible ha SQ-LNS mi iga ed he impac o he d y season on women’s dep essi e symp oms. The d y season is usually he pos -ha es season, he pe iod be o e he nex plan ing season when ood is some imes sca ce and ood insecu i y may be common. Simila ly, among women who deli e ed emale in an s, hose in he LNS g oup ended o ha e lowe dep ession sco es compa ed o hose in he MMN g oup. S udies in India (Pa el e al. 2002), Nige ia (Adewuya e al. 2005) and Tu key (Ekuklu e al. 2004) ha e epo ed PPD o be mo e common among mo he s o emale babies, and his has usually been explained by he socie al p e e ence o male com- pa ed o emale child en. None heless, we canno Table 2 Baseline cha ac e is ics o women by in e en ion g oup, among hose wi h da a on dep ession a 6 mon hs pos pa um Va iable LNS (n=382) a IFA (n=385) a MMN (n=382) a Age (yea s) 27.1 ± 5.5 26.6 ± 5.5 26.8 ± 5.3 Heigh (cm) 159.1 ± 5.4 159 ± 5.7 159 ± 6.1 BMI (kg/m 2 ) 25.2 ± 4.7 24.7 ± 4.5 24.8 ± 4.4 Yea s o o mal educa ion (yea s) 7.6 ± 3.9 7.8 ± 3.5 7.5 ± 3.6 Ma ied o cohabi ing 352 (92.1) 357 (92.7) 361 (94.5) P imipa ous 122 (31.9) 133 (34.5) 123 (32.2) Anaemia (g/L) b 148 (38.7) 164 (42.6) 154 (40.3) Ges a ional age a en olmen (weeks) 16.2 ± 3.3 16.0 ± 3.2 16.3 ± 3.2 Season when dep ession da a collec ed = d y season 185 (48.4) 192 (49.9) 200 (52.4) Child sex = male 190 (49.9) 175 (45.6) 191 (50.0) Household asse index −0.06 ± 1.01 0.03 ± 1.02 0.07 ± 0.94 Housing index −0.02 ± 1.00 0.02 ± 1.02 −0.02 ± 1.02 Household ood insecu i y index 2.4 ± 4.0 2.6 ± 4.4 2.7 ± 4.4 LNS g oup: women we e in ended o ecei e 20 g SQ-LNS wi h same mic onu ien s as he MMN g oup, plus ano he ou mine als (Ca, P, K and Mg) as well as mac onu ien s du ing p egnancy and he i s 6 mon hs pos pa um; IFA g oup: women we e in ended o ecei e 60 mg i on plus 400 μg olic acid du ing p egnancy and a calcium placebo du ing he i s 6 mon hs pos pa um; MMN g oup: women we e in ended o ecei e 1–2RDAs o 18 i amins and mine als (including 20 mg i on) du ing p egnancy and he i s 6 mon hs pos pa um. All h ee supplemen s we e in ended o daily consump ion a Values a e mean ± SD o n(%) b Anaemia based on WHO cu o o 110 g/L Table 3 EPDS sco es a 6 mon hs pos pa um by in e en ion g oup (unadjus ed and adjus ed analysis) LNS IFA MMN Compa ison be ween IFA s LNS Compa ison be ween MMN s LNS Compa ison be ween IFA s MMN Median (Q1–Q3) a Median (Q1–Q3) Median (Q1–Q3) P alue b Di e ence (95% CI) P alue Di e ence (95% CI) P alue Di e ence (95% CI) P alue EPDS sco e (unadjus - ed) 4.0 (1.0–8.0) 4.0 (1.0–8.0) 5.0 (2.0–9.0) 0.13 0.03 (−0.17, 0.24) 0.92 0.17 (−0.04, 0.37) 0.14 −0.13 (−0.34, 0.07) 0.28 EPDS sco e (adjus ed) c 0.17 0.02 (−0.18, 0.22) 0.97 0.15 (−0.05, 0.35) 0.19 −0.13 (−0.33, 0.07) 0.29 LNS g oup: women we e in ended o ecei e 20 g SQ-LNS wi h same mic onu ien s as he MMN g oup, plus ano he ou mine als (Ca, P, K and Mg) as well as mac onu ien s du ing p egnancy and he i s 6 mon hs pos pa um; IFA g oup: women we e in ended o ecei e 60 mg i on plus 400 μg olic acid du ing p egnancy and a calcium placebo du ing he i s 6 mon hs pos pa um; MMN g oup: women we e in ended o ecei e 1–2RDAso 18 i amins and mine als (including 20 mg i on) du ing p egnancy and he i s 6 mon hs pos pa um. All h ee supplemen s we e in ended o daily consump ion EPDS Edinbu gh Pos na al Dep ession Scale a Median (25–75 pe cen ile) b The EPDS sco es we e squa e- oo ans o med o he analysis. Repo ed P alues a e o he ans o med sco es c Adjus ed o household ood insecu i y index Lipid-based nu ien supplemen a ion and pos pa um dep ession 61 comple ely ule ou he possibili y ha he in e ac ion e- sul s may be spu ious. S eng hs o ou s udy include he andomized design o he ial, blinding o s udy pa icipan s o IFA/MMN ea men , la ge sample size, long ollow-up and low d op-ou a e. The e we e a ew limi a ions ha wa an men ion. Fi s , we did no ha e da a on he dep ession symp oms in ou sample a baseline, be o e supplemen a ion. Second, due o he di e - ences be ween he IFA/MMN capsules and SQ-LNS sache s, we we e unable o blind s udy pa icipan s and ield wo ke s o IFA/MMN s SQ-LNS ea men . Howe e , ield wo ke s we e blinded o he s udy hypo hesis and aken h ough egu- la e eshe aining, and da a analys s we e ully blinded o g oup assignmen s un il analyses we e comple ed. Thi dly, in spi e o ou e o o ensu e good quali y da a by o ganizing egula e eshe aining o ou da a collec o s, he possibili y o measu emen e o s ill emains, which could also ha e in luenced ou esul s and es ima e o dep ession in he Ghanaian popula ion. Las ly, in his s udy, we measu ed de- p ession using a sc eening ool ins ead o a diagnos ic in e - iew. We acknowledge ha using a diagnos ic in e iew would ha e inc eased ou con idence in ou esul s, bu we we e limi ed by esou ce cons ain s. I is wo h no ing, how- e e , ha he EPDS sc eening ool has been widely alida ed and used in di e en low-income popula ions including Ghana (Nhiwa iwa e al. 1998;Ok onipae al.2012;S ewa e al. 2016;Uwakwe2003) o measu e symp oms o dep es- sion. We he e o e belie e ha he s udy’s weaknesses do no bias he inding o no associa ion o ma e nal SQ-LNS con- sump ion du ing p egnancy and lac a ion wi h dep essi e symp oms a 6 mon hs pos pa um. In conclusion, his s udy did no p o ide e idence o sup- po he hypo hesis ha supplemen ing ma e nal die wi h SQ- LNS will imp o e ma e nal dep ession sco es a 6 mon hs pos pa um. Howe e , he signi ican in e ac ion wi h season wa an s u he s udy. Table 4 EPDS ≥12 a 6 mon hs pos pa um by in e en ion g oup (unadjus ed and adjus ed analysis) LNS IFA MMN P alue Compa ison be ween IFA s LNS Compa ison be ween MMN s LNS Compa ison be ween IFA s MMN n(%) n(%) n(%) Odds a io (95% CI) P alue Odds a io (95% CI) P alue Odds a io (95% CI) P alue EPDS ≥12 (unadjus ed) 50 (13.1) 43 (11.2) 56 (14.7) 0.35 0.83 (0.50–1.40) 0.69 1.14 (0.70–1.87) 0.80 0.73 (0.44–1.22) 0.32 EPDS ≥12 (adjus ed) a 0.32 0.79 (0.47–1.35) 0.55 1.09 (0.67–1.81) 0.89 0.72 (0.43–1.21) 0.30 LNS g oup: women we e in ended o ecei e 20 g SQ-LNS wi h same mic onu ien s as he MMN g oup, plus ano he ou mine als (Ca, P, K and Mg) as well as mac onu ien s du ing p egnancy and he i s 6 mon hs pos pa um; IFA g oup: women we e in ended o ecei e 60 mg i on plus 400 μg olic acid du ing p egnancy and a calcium placebo du ing he i s 6 mon hs pos pa um; MMN g oup: women we e in ended o ecei e 1–2RDAso 18 i amins and mine als (including 20 mg i on) du ing p egnancy and he i s 6 mon hs pos pa um. All h ee supplemen s we e in ended o daily consump ion EPDS Edinbu gh Pos na al Dep ession Scale a Adjus ed o ma e nal yea s o educa ion and household ood insecu i y index 62 Ok onipa H. e al. Acknowledgemen s We hank he iLiNS S ee ing Commi ee (h p:// ilins.o g), o p o iding leade ship o he iLiNS-DYAD ial; Ma y A imond o he iLiNS P ojec managemen ; Maku Ocansey o supe - ising da a collec ion ac i i ies; Boa eng Banne man o da a manage- men ; Jane M. Pee son o s a is ical assis ance; and he women who pa icipa ed in he s udy. The au ho s’ esponsibili ies we e as ollows, SA-A, AL, PA, SAVand KGD: designed he esea ch; HO, SA-A and AL: conduc ed he esea ch; HO and RRY: pe o med he s a is ical analysis; PA and KGD: ad ised on he analysis; HO and KGD: w o e he manusc ip ; and SA-A, AL, PA, SAV, RRYand KGD: e iewed he d a manusc ip . All au ho s ead and app o ed he inal e sion o manusc ip and accep ed inal esponsibili y o he manusc ip . The unde o he s udy had no ole in he s udy design; he da a collec ion, analysis and in e p e a ion; and he p epa a- ion o he manusc ip . The indings and conclusions con ained wi hin a e hose o he au ho s and do no necessa ily e lec posi ions o policies o he Bill & Melinda Ga es Founda ion. Compliance wi h e hical s anda ds Funding This s udy is unded by a g an o he Uni e si y o Cali o nia, Da is, om he Bill & Melinda Ga es Founda ion. The indings and conclusions con ained wi hin a e hose o he au ho s and do no neces- sa ily e lec posi ions o policies o he Bill & Melinda Ga es Founda ion. Con lic o in e es The au ho s decla e ha hey ha e no con lic o in e es . E hical app o al The s udy was app o ed by he ins i u ional e iew boa ds o he Uni e si y o Cali o nia, Da is; Ghana Heal h Se ice; and Uni e si y o Ghana Noguchi Memo ial Ins i u e o Medical Resea ch. In o med consen In o med consen was ob ained om all indi idual pa icipan s included in he s udy. 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