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.
Open Access This a icle is dis ibu ed unde he e ms o he C ea i e
Commons A ibu ion 4.0 In e na ional License (h p://
Lipid-based nu ien supplemen a ion and pos pa um dep ession 63
c ea i ecommons.o g/licenses/by/4.0/), which pe mi s un es ic ed use,
dis ibu ion, and ep oduc ion in any medium, p o ided you gi e app o-
p ia e c edi o he o iginal au ho (s) and he sou ce, p o ide a link o he
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