The odour of human milk: Its chemical variability and detection by newborns Hélène Loos, Daniela Reger, Benoist Schaal

To cite this version:

Hélène Loos, Daniela Reger, Benoist Schaal. The odour of human milk: Its chemical variability and detection by newborns. Physiology & Behavior, 2019, 199, pp.88-99. ￿10.1016/j.physbeh.2018.11.008￿. ￿hal-02414388￿

HAL Id: hal-02414388 https://hal.archives-ouvertes.fr/hal-02414388 Submitted on 25 May 2020

HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability journal pertain. be it manuscript a This https://doi.or of Please Accepted date: Revised date: Received date: T Reference: DOI: PII: Helene M.Loos,DanielaReger by newborns The Accepted Manuscript o appearin: is service discovered human published odour is cite a PDF to of will this milk: g/10.1016/j.physbeh.2018.1 our human in which file under article customers its Its of Comment citer cedocument: final could milk: go an chemical as: copyediting, 5 November2018 29 October2018 12 August2018 Physiology &Behavior PHB 12358 https://doi.or S0031-9384(18)30640-1 unedited form. Helene Its af we fect chemical , BenoistSchaal

Please are variability the manuscript M. providing g/10.1016/j.physbeh.2018.1 typesetting, content, Loos, note 1.008 variability that and Daniela that this and during and detection has early all and Reger review legal been the detection version production , disclaimers accepted by Benoist of the newborns. 1.008 of resulting the Schaal for process that manuscript. publication. Phb proof apply , errors The (2018), before to odour may The the As Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability Corresponding author: HeleneLoos, e E CNRS c GiggenhauserStr. 35, 85354 b 910549, Erlangen, Germany a H by detection newborns odourThe ofhumanmilk relationships” Physiology & Behavior, special issue role"The of body odors and olfaction ininterpersonal

- Developmental Ethology and Cognitive Psychology Group, Centerfor Taste, Smell and Food Science, Chair of Aroma and Smell Research, Friedrich Sensory Analytics Sensory Department, Fraunhofer Institute for Process Engineering and Packaging IVV, e Mail: [email protected],[email protected], benoist. l e ne M. - Universitéde Bourgogne,9E bd Jeanned’Arc, 21000 Dijon, France Loos

a,b , D

ACCEPTED MANUSCRIPTaniela ACCEPTED MANUSCRIPT Comment citer cedocument:

Reg . Freising, Germany

er

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Benoist - mail: [email protected]

: Schaal its -

Alexander chemical c

- Universität Erlangen

variability and schaal@u

- Nürnberg, Henkestr. - bourgogne.fr

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability Declaration O Hum Keywords of odor and addressing changesin milk odour dueto storage, lactational stage, and influencing milk odo feeding context inodour the initiation Human milk hasodour for long elicited research interestwith regard to itsfunction inbreas Abstract dour. an

, M ous substancesous

.

Thepresent review aims to providean overview ilk, s

human of interest: N eonat . Further, an overview of the current knowledge of odorant composition and factors

ACCEPTED MANUSCRIPTurprovided is neonate, considering different typesof response measures e, . ACCEPTED MANUSCRIPT

We finally highlightsome B ehaviour, Gas C none. Comment citer cedocument:

by summarizing

hromatography issues for results - Olfactometry/Mass S

from analytical studies ofbehavioural the effects of

future research.

maternal pectrometry

infeeding a non or

using olfactometry dietary intake human , Body tfeeding milk milk - , Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability positively (i.e., by neonates inneonate’s a and nursling’s life,generally being their sole nourishment,is it tempting to expect mammary lactogenesis) which occurs around the thirdafter day parturition in humans, and Colostrumthe is breast fluid obtainedbeforethe 2. milk odour the research ethology, (hereinafter: and a review on the current knowledgeof In development some anot life however, is perceptual and behavioural effects. interaction food of odorants with the formation and a Food 1. Introduction the following, we Human n

and comesalong with close mother chemosensory milk milk odo herfacet conspecificinformation roma scientists elucidate the chemical structureof food odorants,

both within

to detectthe odours of these breast secretions and to behaviourally respond developmental secretion ingestedthe by neonate. .

eonates’ responses to human milk odour

a u colostrum and

special food for at leasttwo reasons. First,its consumptionrestricted is to early human of theof infant’s brain and body is added r

of , and ii)

their releasefrom food the matrix. appetenceand acceptance) and chemical

ACCEPTED MANUSCRIPTtakean interdisciplinary each field

ACCEPTED MANUSCRIPT to the chemical nature Comment citer cedocument: psycho research on milk)

thatimplicated is in

a biology and nd principles .

W

at theirat interface This also hol e aim to

: organism human milk odour, namely the question

i) - infant interaction the neonatal perception underlying

of of function food perspective to identify the p . Considering the odorous co In , considering ds true for research on the presentreview second chemistry stimulating s . T .

We specificallyWe aim to stimulateresearch hey the

secretory phase . Second,is it of human origin. Th

behavioural and physiological function further its rincipal findings inthe

human milk odour research by providing , and fruitful questions future for ensuing

mpounds si sucking behaviour and gnificance

and reaction to investigatethe biochemical , metaboli

we aim to

of milk aroma milk , and thesignificance and

of lactationof human the c responsesc

of examine

is human whetherit conveys respective principles of their colostrum and . Human milk, thus the first

in favouring ( stage II to them

the current colostrum , and ereby,

fields

of

into

milk s

milk the

of of

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability Whereasdurat the colostrum or as milk postnatal the stimulus, and 20 drops amnioticof fluid as the prenatal stimulus. compared to odours stimuli nextThe th response are detected by 2 ( replacedwas bystimulus a bearing 20 drops of theirof mother’s milk compared to an odourless control newborns drops of their mother’s colostrum compared to an aqueous odourlesscontrol the odours colostrumof by researchers time towards stimuli. to lactating mothers. He In 197 2.1 unlesssuch potential knowledge o hereinafter: unfamiliar milk; em, some 2 Schaal Head orientation and oral movementsin -

to 7 5 collected

, Macfarlane Theneonates discriminated between these twostimuli by turning theirhead forlonger a ; - question maternal

and colleagues day

and third, that 4 oriented longer and showed longer mouthing movementsto a stimulus bearing 20 drops

, to assess neonatal responses to various stimuli stimuli havebeen informat n - the breast pad than to the control.

old neonatal responses to the odours of colostrum and alone, milk disregarding other from different body sites - newborns, recordingduration the of headorientation towards each of these

to ask to ion headof orientation towards theone or the other stimulus not was and mammary

ACCEPTED MANUSCRIPT

[4] from thepostnatal environment

ion 4 simultaneously present - ACCEPTED MANUSCRIPT

day pioneer

and , (odour familiarity, quality) differs between the milksfrom different women i Comment citer cedocument: s 2 - - how neonates how behave when simultaneously exposed to two maternal - day old neonates day

milk. [5, 6]

directly - - ed neonateinfant responsiveness to the odo old infants recognizetheir mother’s milk odour old

sources of olfactory information The ). Theseresul

infants wereshown display to

compared with

neonates ;

, e.g. second, that the double choice tests ed

to the ts imply,ts first, that the odours of colostrum and milk

an odorous breast pad and an odourless control pad turn This maternal

age ed

. This question was addressed using drops 20 of

approach was taken on milk -

matched milk their head . T . se his alsowas the case when the control

odours

including milk

odours elicitan orienting and mouthing

non

longer tostimulus a bearing 20 from ( otherwise

from a - random responses toward the prenatal . Thus, u notherwoman and refined

r of the breast [5] review , meaning . inseries a of studies Similarly ed in environment that by other , 4 [1

of - - 3] day for

their ) ,

- s old

as .

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability neonates evinced odour, and showed searchmore mode(bottle or breast), thenewborns oriented longer and shorter with latency towards the milk formula presented 3 includingodour the It remains to askabout the relativeattractiveness of milkodour with regard to non neck breastor odours. of milk elicits ori discussion possibleof underlying mechanisms),and, second, that, in 3 attractiveness theover odour amniot of Taken together, these resultssuggest, first, that the odour of to the b opposed to breast odour, 3 preferential orientation or di theiror mother’s milk and areola odour werepaired, 3 experienced Human infants’responses alsohave been tested when simultaneously exposed to formula ( who oriented longertowards amniotic the fluid stimulus day on 4 it when was paired with their respectively; own mother related responsiveness towards simultaneously presented prenatal and postnatal odour cues of their head significantly longerto the postnatal stimulus, i.e.,the milkstimulus birth discriminativein three groups breast of , respectively, two othergroups neonates,of testeda at mean age of 85 and 114 reast odour

(i.e., formula that hadbeen not ingested by theinfants before) [8] ; see; also -

s

postnatal [5]

to was replicated two with other groups of neonates (mean age: 42 and hours, 91

). However, suchshift a in behavioural responsedid not inoccur bottle 4 enting and mouthing responses that areequivalent to thoseelicited by maternal -

day enhanced s

ACCEPTED MANUSCRIPT[10]

of - [9] ly in the context breastfeeding.of old infantswith milk of a

ACCEPTED MANUSCRIPT animal and milk . ).

Comment citer cedocument:

- day head scriminative mouthing respo - old neonatestended to orient their head more often, yet no longer, - like mouthing movements to it.Simil orientation and scanning/mouthing activation towards milk

- ic fluid during thefirstfew postnatal days (see animal milk fed neonates a with mean age of 10, 34, and 55 hours n unfamiliar - based - day

When their mother’s milkand neck odour, nse formula - mother and old newborns did notshow any [10] mammary . However, when milk odour was s .

Marlier - arly, 3 day . Irrespective of the feeding unfamiliar secretions gains - old neonates,the odour -

and to [7]

4 . Thisresult of age Schaal -

day

two odours bovine milk - maternal odours, - hours, oriented old bottle [7] - fed infants [11]

for a

odour odour - after based - their fed - Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability 2.2 2.2 mother the relativeattractiveness of milk odour compared to postnatalother odours odour mixtures as compared to formula odour, and analogous results were obtained and breast beto barely behaviourally discriminate fluid. In contrast to this,differentpostnatal maternal odours milk) transitional milk change has not colostrum elicitsneonatal orienting and mouthing responseas early as dayon two In two sum, renders is paired with anon conclude,first, that 3 breastfeeding i test performedwas with a group infants of having been exposed to thechamomile scent during movementstowards their mother’s milkodour than to the chamomile odour. However, when the [12] andodour a chamomile scent fed sincebirth from anunfamiliar mother (Non)

showed that

becoming s

, and similarly to non been i

the lear with the newborn’s age - nutritivesucking infeeding a context - fed 3 - choicetests including human milk nvestigated, date)to

[11] ndays the before, no such discriminativerespon

more attractive to 3 associated with ned odour as attractiveas

- (milksecreted in the

breast to . -

ACCEPTED MANUSCRIPT Otherwise, s maternal odour, and, second, that associativelearning during breastfeeding 4 - -

day to ACCEPTED MANUSCRIPT -

fed infant 4 Comment citer cedocument: - -

old neonates orient longer and show more mouthing to the odour of milk as compared to the iso day - c

onspecific odours, appears still (conveyed by - old neonatespreferentially orient towards human milk odour it when breastfeeding. tudying 3 and s turned their head longerand . Therelative salience prenatalof and postnatal odour cues -

with to several day

d at this age

4 - - day the the odour of

to a

- cream 4 lactational old breast odour

Despitethis evidence,however, our understanding of -

day - long - intenseodour theof formula milk they had been

- (butmore testsare needed)

old neonates’ behaviour in a test opposing milk applied the on areola) as a stimulusas a haveshown thatthe odour of transition between colo milk. - fed neonates than the odour amnioticof stage of milk secretion, the odour of

(milk,breast, and neck odours)

incomplete. se expressed

was observed with low

, Delaun longermouthing

associated with the - strum and mature intensityartificial . Finally, bottle both [12]

(earlierbehaviour ay . Onecan thus - El Allam et al.

appear -

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability to to inbreast a Finally, Doucetet al. in milk comparison with formula consistent outcome theseof studies washigher a respiration frequency orno only marginal differences werereported (i.e., m of odour condition and the water control condition. frequency when their mother’s milk odour w their mothers sincebirth monitored inbottle a ingested more at milk a later breastfeeding session. Nutritive sucking parameters werefurther morefrequent long control group,regularly the exposed infantsevinced longer the initial breast 31.2 weeks), human on a group stimulated releasing pacifier was enhanced based milk formula milk gestational age in effectThe of milk odour suckingon or searching behaviour in a feeding context hasbeeninvestigated infantsborn at term and

term avoid ce (thawed breast milk rtain experimental parameters (e.g., familiarity of formula odour, origin ilk odorants werereleased intraorally and reached the olfactory areas retronasally) milk).In another study on 2 infants when being fedformula and the nursing position

release of Raimbault et al.

(GA) feeding trials influence ) with formula (

sucking bouts ACCEPTED MANUSCRIPT : during nasal tubefeeding this of non milk,

[19] - 30.3 weeks) feeding session with 12 ACCEPTED MANUSCRIPT milk

charged [15] tested the behaviour of 3 Comment citer cedocument:

. The breast. The was part - in

or breastor

. The newborns. The evinced a higherexpression pressureand sucking [14] infantsborn

compared to a control condition [16

mean mean

with were orthonasally stimulated with the odour of fortified breast investig (i.e., bouts composed of -

- to 5 18] - related

a s GA

. - fortifier powdercontaining similar constituents as bovine the neonates’ week

ated how exposureto their mother’s milkodour justbefore preterm. Thus, :

29.3 weeks; milk without as - volatiles day - concerning old preterms presented ly Otherresearchers compared thesucking behaviour

- or completelyor covered by a old - day

term , or , or to selectively release odorantsfrom the

breastfeeding behaviour. - old neonates when facing their mother’s [13]

additional

when 24 orthonasally, as compared to the formula the neonates’ sucking behaviour, a 7

maximal durations of infants hadwho been separated from

). Thestudy, however, lacks ( or or more sucking movements) mean - nutritivesucking theon odour .

S - uch an effect notwas observed day GA orthonasal

- of theof two groups

old preterm when the neonates were fed and storageduration transparen odour C

sucking bouts and ompared to the

infant stimulation

information t : : 31.8 and . , and s plastic film Whereas

(mean -

- in of Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability experienceskin contact,including suckling, anaveragefor 64 of minutes the first 24 hours orangejuice, and Allwater. neonateshad been separated from their mothers and bottle colostrum newborns weresequentially presented responses comparable to those towards milk odour actions physiologicalor responses administration are substrate neonatal Sequential testspermit administering numerous odours to neonates 2.3 deserves relativepotency to stimulate sucking with regard to other maternal and non (preterm birth) number low studiesof and nutritive sucking inafeeding context.However, this conclusion appears In these sum, results enhanced in the “ major influence on oral activation or other behaviours, the with exception rooting,of which was the type of odorous condition (“ parameters (e.g., crying time, duration of opening theeyes,duration licking,of sucking and rooting), odorous conditions was differentfrom their b nipplefrom only, the areola only, or from milk only Oral movements

responses to milk odour, the stimulus set further s, s

/ milk pecific . - to Hence, the effect of milk odour nutritiveon sucking inafeeding context,and its , study. . thecolostrum / total

T -

designed judge to stimulus’ a relative efficacy skin contact sucklingor beforebeing separated from the mothers. odours heneonates

ACCEPTED MANUSCRIPT,

indicate facial expressions ACCEPTED MANUSCRIPT breast” condition compared to the “areola

Comment citer cedocument: or often often

that milk butodour, not odorants

total were d the special lifeearly circumstances theof participating newborns milk , and have been used screen to f breast”, “areola

from anunfamiliar mother

, and an odourlesscontrol.

, and ivided into two groups. Whereas on

both physiological responses ehaviour in the odourlesscondition a for range of

day 1 and4 day postpartum . Whereasnewborns’ the behaviour in the generally comprised additional .

I nstudy by a Mizuno etal.

only formula odour water,or promotes(non)

immediately ”, ”, “nipple , formula to

Studies using sequent only or odorants thatmay elicit

induc

only , in sequential tests

and afterbirth ” and” “milk

provisional ”, “milk group Ahad skin e in thosestudies

(origin specified) not specificneonatal facial

- with their mothers maternal odours, still [20]

, groupdid B not only

only maternal dairyor , two groups of in view theof ”) did ”) nothav

On day 4, ” ” condition

ial stimulus - fed during -

to assess - skin - ’ ,

ing s

e ae .

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability the inconsiste iso odours isoof infants,and the respiratory responsesto milk and formula appeared to be modulated by the feeding mode theof andodour to the odourless control, indicatin neonates. breathing rate changeto unfamiliar milk than to unfamiliar formula, and smelling butanoic acid the control. respiratory rate werehigher for th muscle movements according t to behavi discriminativeresponses occurred with regard to the skin temperature. their breathing rate and skin temperature to assessphysiological responsesto the odour stimuli. vanillin and butanoic acid neonates the responses of whom were compared for unfamiliar milk evidence of milk this hasnotbeen replicated inother studies. Thus, in a studyconductedSoussignan by a non familiar and unfamiliar higherwas to colostrum / the4, twogroups evinced a highermouthing frequency to the own mother’s colostrum and unfamiliar colostrum the g roup - intensity theof stimuli ( unfamiliar -

dairy odour (orangejuice), and the odourless control stimulus as early as onHowever,1. day A, butnot ourally activeneonates, the duration of facial displa Thus, even ifSoussignanal. et

milk Further, -

intense vanillin and butanoic acid. One mightspeculate that this result isrelated to the nciesin therelative efficacy of milk,formula, other odor the odour of

milk responses towards milk odour -

than to group specificfacial responsiveness was obtained in 3

ACCEPTED MANUSCRIPT odour more neonates showed odo ACCEPTED MANUSCRIPT human B, showed more frequent mouthing to the theodours of

Comment citer cedocument: . odours

In groups, both n u f cf. ormula than to r than water. [23] milk milk odour leads to a highermouthing frequency than formula odour, . In add heFacial Action Coding System ) e threee odorous stimuli (milk, vanillin, and butanoic acid) than for , to theor presence of these

formula, orangejuice, and water,and the mouthing frequency ition toneonates’ the behaviour, the authors also recorded [21] I n the same study, breast

that of o discriminative responsiveness to the odours of their

g perception of milk byodour the neonates,

disgustexpressions ( found distinctfacial and respiratory responses to milk did not

orangejuiceand water. was evident da on

significantly ys, theys, number of action units (

odours odours familiarof and unfamiliar

two odorantsin milk -

[22] to 4 facial ir own - differ from those towards the fed neonates evinced

y 1. odour ) - ant , andincrease the in day action units 9 and 1 Theproportion of

mother’s milk vice versa Further, both on days 1 and s, and the odourless control -

old breast These , water,and iso resultsindicate that

in bottle

- (cf.

and bottle

et al. et odour [12] the a higher distinct - 0 intense - fed ) [21] )

. when than to

Yet,

- , no No fed Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability concentration differed from those elicitedthe by familiar feed of the newborns diddi not based formula) stud respons Inmore a recent work stimuli, formula, vanillin, andcontrol the apparently did notbehaviourally discriminate efficacy of AGsecretions secretions than to unfamiliar milk bottle human pasteurized upon stimulus administration and familiar of food duringactions Amongstothers, they Further, the stimulus setcomprised unfamiliar milk, sebum, and areolar gland (AG)secretions. familiar administration Recording oro stimulation,odour whereas Soussignan etal. presentation. For instance, Mizuno etal. differentstudies induceto sucking or other facial expressionsalso may bedue to different methods ies - fed butnot breast , t milk. es food (milk formula),or unfamiliar formula, non heneonates ffer

to cow milkodour ledt Whereasno significantstimulus

aqueous solutions s of between - - , Doucet al.et the10 dependent cephalicresponses, respiratory parameters and heart rate during sequential stimulus

as compared to the odourless control water , e.g., regarding the

ACCEPTED MANUSCRIPT.

A - s did not enhance oral movemen observed , nalogous results were obtained for the maximum change inspiratoryof rate

- ACCEPTED MANUSCRIPT any of 3 stimulus presentationhigher to a extent - - in day Comment citer cedocument: fed neonates evinced ahigherincrease in heartrate to the odour . For example,For the compound 3

induc - [24] . Further, old the stimuli

that o a higher a o oro ing

neonates investigated and teroids, acids,and thiols

neonate’s neonatal physiologicalneonatal and behavioural activation. Yet, the odour

to

in . . [20]

the

the C

ertain of theodorous stimuli were studied by Loos al. et ir familiar food -

[21] 10 specific alteration respiratoryof ratebecame evident, recorded the

bet responses - behavioural state of unfamiliarof AG cephalic activation than the odour unfamiliar of - s

ween milk odour and the odours of other maternal - admini period ts to their - pasteurized cow milk, vanillin, and water.

stered the odour stimuli -

of 3 afterstimulus presentation, hydroxy mouthing frequency during120 a . , and the respiratory rate theof neonates

occurring in milk and Theseresults point towards high a - day

familiar feed

secretions activated oro than the odours unfamiliar of milk , but or or the - - old infants 3 - methylhexanoic acid,

the [25, 26]

duration stimulusof

led to se

response

(milkor bovine milk to theodours the of

facial with regard to

/or for for 10

applied in the responsesthat

s sweat

non appeared

s each. - cephalic - a . of AG of neonates In th

s their -

long

e - ir s

e

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability cephalic movements,as compared to the odours of unfamiliar and milk odour unfamiliarof AG secretions was found to elicit a distinct neonatal response,i.e. longer oro performed; sequential tests [20] and availableThe evidence concentration mixtures and milk formula odours were reported only inpart ofstudies. the With regard to other odo sequential stimulus design. In no sum, consistent pictureis emerging from thecurrently available t newborns upon stimulation with recent observed for vanillin which elicitedcortical a notthis was the forcase infantsolder than h. No24 such age haemoglobin when presented with their own mother’s colostrum odour compared tothe control, brain.neonatal Using near other species identityodour familiarities, and qua Such concentration responses contributor . that thisresponseis dependent on

Yet, this was NIRS

or or odorants, neonatal re , irrespective theof feeding mode.

than familiar food it when presentedwas - infrared spectroscopy

[21] to sweatodour study, Aoyamaal. et , .

on a behavioural a on

[29, 30]

Whereas ), wereamniotic fluid (

unfamiliar sebum and AGsecretions notreplicated by Doucetet al. -

ACCEPTED MANUSCRIPT dependent effects may relate to differentperceived intensities,odour lities

. familiar milk

ACCEPTED MANUSCRIPT furtherindicate Such c

newborns youngerthan 24 h showed ahighe Comment citer cedocument:

[27, 28]

Discriminativeresponses to milk odour and the odourless control, to or supposed to occur in milk oncentration or [34]

sponses appear to depend on the nature theof stimulus (NIRS) , reflecting thatconcentration

neuronal level

odour than with yet,no statistical comparison

found that

s the neonates’ postpartum experience of

, Bartocci etal. that the own mother’s milkodour is reco - dependentresponsiveness to odorants

m etabolic

the changein oxygenated haemoglobin was higher [24] [31, 32]

formula at 50 ng/L . , elici

Maternal stimuli other than milk [24]

[33] activation inall infants .

ted a longer duration of negative oro ,

an studied processing of odours

in a sample aboutof 5 - dependent responsiveness was d familiar sweat , butnot at 0.5 ng/L or at 200 is put forward to

to responses to milk o r change in oxygenated estsusing milk odour ina the familiar feed theof

at any age [26]

maternal odours gnized contribute to

. - is also evident

day From these,the

- applied in old on

. dour by the

, In a more

and day 4,

rant µg/L.

was

its - facial -

in Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability odour term neonates during a familiar odours. newborns responses during venipuncture and supportrecovery a heelafter However formula in Analogousodour. results were obtained by Badieeet al. increased ininfants of the control group (saline) butnot in the group exposed to their mother’s milk second experiment,the general motor activity, and newborns own mother’s milk, colleagues exposed to a sampleof preterm olfactory cues. medical tests,and it hasbeen investigated whether Heel pricks 2.4 implemented in origi S neonates. equential testsare promising sincethey allow multiplecomparisons between stimuli of different Facial expressions ns. Yet,it appears that , an unfamiliar vanilla odour, and ,

it has also been demonstrated thatfamiliar a non [38] undergoingheel a two groups

[36] and venipuncture the . ir

Indeed, de Chanville etal. compared thesoothing effects Hence

I future studies. familiar milk n 2005, Rattaz etal. the milkof anunfamiliar mother

ACCEPTED MANUSCRIPT infant , , subsequent studies aimed atcomparing the soothing effectof and milk other

of pretermof newborns motor activation, ACCEPTED MANUSCRIPT heel same Comment citer cedocument: s (

the crying and grimacing time,compared as to the other conditions.

prick median prick are used as a routineprocedure to obtain neonatal blood samplesfor odour authors furthershowed the that salivary cortisol concentration was

methodological

procedure procedure

as compared to an odourless condition.

GA [39]

a dry control

:and 32.4 33.6 weeks)undergoing venipuncture crying

[35] investigatedbehaviour the of

(mean , smell . The own mother’s milk reducedodour significantly

reportlower pain scores and shortercrying duration in , and physiological responses on day 5 standard ing GA related , respectively , formula, : 43.1 : and 43.5 weeks) the own mother’s milk, - old newborns [37] for testingfor newborns - p maternal odour can alleviate pain

ain for the and saline, inasample of responses

. prickprocedure

Comparing the effects familiarof

effect of of

4 groups4 of the odours of either can bediminished by

in a pain context Similarly

. familiar

should be a familiar

in preterm 3 - , Nishitani and milk day

vanilla term while being -

old odour

In a

-

their full born

and - Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability breastfeeding success, growth, and positiveperception the of infant’s behaviour by the mother, show Fromabove the cited research 2.5 whether processe both system, inborn mechanisms stressof and pain buffering inneonates responses. compared to the odourless condition, familiar odours alsohave been shown to reduceneonatal pain pa neonatal Taken together, these studiessuggest that smelling saline. smelling their mother’s milkthan inbottle [41] the vanil groups same study, familiarwith a vanilla odour no or odour (mean lower increasein heart rateand lower decreasein blood oxygen saturation than infantspresented venipuncture intervention that 10 maternal odours than thosesmelling duringheel the vanilla odour to those of milkodour, the infantsshowed equivalent crying and facial activity. Yet, Conclusions

demonstrated that recovery from venipuncture was more efficient in calming,

both during and aftervenipuncture.

or ifthe familiarity itsof chemical signatureis la group reducedwas

Thus, itremains to in responses than unfamiliar

pain orienting

prick

(or with less vs. more intense odours) responses

ACCEPTED MANUSCRIPT thefamiliar vanilla odour

procedure,infants smelling the milk odour moved their head to a lower extent ACCEPTED MANUSCRIPT s areinvolved ,

and appetitivebehaviour towards it Comment citer cedocument: in

ascertain the milk group w , during, butnot after the procedure.

we - day can

sequentially simultaneouslyor -

old preterm deducethat neonates detect the odour of

whetherhuman human -

fed neonatessmelling their formula andcontrol group a familiar

In comparison to thecontrol group, t , indicatingdifferent abehaviour with maternal nonvs ere GA milk, formula, and familiar odo

: 31.6, 30.9, and 31.5 weeks,respectively). human significantly reduced compared to the two other infantsinbreastmilk the condition showed a sufficient . Neshat etal. milk milk milk milk odour , e.g., related to the endogenous opioid . carries s Sincesuch behaviour results in

to elicit the same effects, finallyor

F . inally [40]

omecomponents that affect

is moreefficient in alleviating

, Mellier and colleagues

reported a for breast rants. - hepain responsein fed human

term Nonetheless, as milkand neonates In

m the ilk - Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability milk stimulus milk used for behavioural assays. quality of milk odour odorants In view ofbehavioural the responses of human neonatesto milk odour, one mightask which stimuli experimental conditions, e.g., response measure odours. postnatal odour landscape, and to expand knowledgeour neonatalon behavio manner then capable o the first postnatal days offerhighly reinforcing conditions for learning.odour 45] related breastfeedingto not presence driver (pre)of behaviour. Whereas one mayexpect information aboutthe presence of food to bea different,but also the responses studying infantrespo Accordingly,neonates ingestive (head orientation, non tests and inexperimental research Thereby, odour ), thesestudies thus demonstratethat human newborns arehighly sensitive to odours and that

restricted to milk odour. Asindicated by the above and sequential tests mostly aim quantifying at is considered indirecto , blindnessor of experimenters

In doing this,future studies should exercisedue diligence to as milk odour

the nature neoof in might . One might human - ingestivebehaviour, familiarity an of odour f

induce influenc

milk ACCEPTED MANUSCRIPT , since the nsivenessinpain a context, milk odour hasbeen demonstrated to

. speculatethat not only the behavioural response supposed

are generally

ACCEPTED MANUSCRIPT Thus calming ing

guidethis behaviour. or interaction with the mother Comment citer cedocument: natal

the newborn’s behaviour insimilar a manner , it remains, it of interestto

depend tly promote and

maternal diet of - respons dimension of nutritivesucking) and ingestive(nutritive sucking)behaviour. the infant while

stud s

regarding the stimulus presented

on the on iveness ied in

, lactation stage

One posed chemosensory maintain the

to milkodour is expected beto context s , behavioural stateand age of theinfants, choice of

experiencing pain. pre should

responses question, design, and carve out the significance of milk odour in the - - prandial state cited studies . Together with otherresearch (e.g., mother

also also or information about the mother’s

information or storageor conditions might

assess related to feeding including pre - infantinteraction and attachment. ,

multiple aspects of

in these tests. neonates which factors S uch

. in these differentsettings

or even or an equivalent underly

setting. responses

The learnedThe odours

ur towards non rapidlyacquire odours ing

D

influenceth In contrast, when ouble

the respective reinforcing are reducepain - the appropriate, , however, impact - choice [12, 42 - - milk milk e

the are

is

-

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability hypothesized to originate from phenols, acids, he S detected sti O adult human nose,as determined gasvia chromatography cleav haveodour been detec quantitative variations v compounds originating heterocyclic compounds degradation lipidsof co Knowing the 56] the occurrenceand function of microRNA constituentscomprise minerals [46] The main constituents of mature 3.1 3. tructurally diverse odorantscontribute to milk odour, including aldehydes, ketones,terpenes, olatile compounds /MS r bar sorptive extraction from the headspace and from the milk. ntain H , Odorous volatiles of milk ), uman milk odour carbohydrates: age.

; proteins (0. [72, 73]

diverseodorous structures,including compounds from derived oxidative

with th The present review

(e.g., from blood

may be

secretion ).

[51] e Extraction methods used in combination with GC 9 terocyclic structures s - e 2.8 %

[57]

occur ), ACCEPTEDsynthesized and secreted MANUSCRIPT

technique (

e.g., and

, and

ACCEPTED MANUSCRIPT pathways [1, 61 ted in milk , )

; , minerals and vitamins: Comment citer cedocument:

[46] in milk and cells and vesicles fatty acids, aldehydes, ketones,lactones

lipophilic environmental

- , however, 70] ), and carbohydrates( s

milk milk known

and is given in table 1

. , important with inter [60] milk are milk Further, amino acid conjugatesknown as precursors sweatof [71]

vitamins macro oligosaccharides( and t , , and might analogously contribute to milk afterodour

biosynthetic routes degradationor processes,such as lipid and steroids.

focuses water, lactose(5.2 he overall composition of milk -

( and micronutrients see

(

e.g., by e.g.,

on thoseon [58, 59] [52] the .

[48] pyranones,furanones ). S mammary contaminants everal of thesecompounds can be average - E )

, xcellent and intra ) freeamino acids(see . milk

- olfactometry - 7.0 %

volatiles 16 g/L;

( or recent e.g., - - individual

O comprise skin . ; A compilation of odorants ), F [46] urther amino acids proteins: [47] gland reviews areavailable covering thatare ), tr /mass spectrometry , ) onecan expect , ). as well as ,

iglycerides(2.5 qualitativeand Quantitatively minor s some .

solvent [49, 50] Inde [53, 54]

perceivable by an and/ ( e odorous ed, v .g., compounds or or enzymatic extraction, and ), , aldehydes, lipids: arious extracellular

milk to milk - 6.4 %

(GC

[55, - ;

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability milk after milk maternal indole; β oxidation - ionone; [78, 79] ( [76, 77] e.g., ( ). Others, however, likely areenvironmental contaminants being transferred into the E ) ), carbohydrateor aminoor acid degradation (e.g., furaneol, 2 - 4,5

ACCEPTED MANUSCRIPT dermal, - epoxy ACCEPTED MANUSCRIPT Comment citer cedocument: oral oral inhalatoryor uptake(e.g., 2 - ( E ) - dec - 2 -

enal, 1 - oct en - 3 - one;

[74, 75] - bromophenol; ) , carotenoid degradation (e.g., [80, 81] - acetyl ).

- 1 - pyrrolin, Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Nonanal ( 2 Oct Octanal ( ( Hex Hexanal Diacetyl Methylpropanal Compound listed. theirof retention index, determined on capillary column FFAP. description, retent Table1: Odorous compounds detected in milk Z Z Z - Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability ) ) ) Acetyl - - - 1,5 4 H - - 1 1 - ex Heptenal - -

en - en - Octadien

3

-

- 1 - - 3 3 enal - - pyrroline

- one one

- 3 - ion index(RI) capillaryon columns FFAPand DB one

Comment citer cedocument:

citrus geranium leaf roasty, popcorn ACCEPTEDmushroom soapy, citrus fishy, fatty grassy,green MANUSCRIPTglue grassy butter malty Odour - like, metallic -

like, soapy -

description like

- like - (references like - like, metallic

- like

ACCEPTED MANUSCRIPT [82

-

86] Certain odorants beenhave olfactorily detected 1385 1372 1339 1289 1270 1233 1131 1086 1079 981 821 RI FFAP ) -

5, 5, extraction technique,and best identification criterion and colostrum

1103 984 925 975 1000 896 805 775 801 596 552 RI DB

- 5

samples a, b a, b b a, b a, b b b a a, b a, b a Extraction technique

(reference [87] 1)

)

by GC a a b a a b a a a a a I dentif

butnot identified by theauthors, theseare not - O ication criterion

and GC . -

O The odorantsare listed in the order /MS , withreported the odour 2)

[82] [82] [87] [82] [82] [84] [84] [82] [82] [82] [82] Reference

, , , , , , , ,

[87] [87] [87] [87] [85] [85] [84] [87]

, , , , [84] [84] 3) [84] [85]

, ,

,

[85] [85] [85]

, [86]

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Phenylacetaldehyde ( Butanoic acid ( ( Linalool ( 3 ( Decanal 3 acidAcetic 2 ( Non N E E E E Z E - - - Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability onan ) , , , ) ) Isobut Methylthio Ethyl Z E Z - - - 2 Non 2 ) ) ) ------1 2,4 Nona Octa Nonenal Octenal - - en - 2 - 3,5

yl - 2 - Nonadienal one - - - - 3 enal - 2,4 2

- 2,6 - dimethylpyrazine - one methoxypyrazine -

-

propanal - dienal

dienal

Comment citer cedocument:

honey fatty cheesy fatty cucumber flowery fatty, green bellpepper fatty, green citrus potatocooked vinegar green, fatty f mushroom milky ACCEPTED MANUSCRIPT atty, perfume

- - like,

like -

like

-

like,fatty - soapy - like

like - -

like like

ACCEPTED MANUSCRIPT 1395 n.a. 1642 1640 1615 1585 1583 1540 1527 1517 1498 1497 1458 1451 1455 1423

1077 n.a. 1047 1193 818 1110 1154 1103 1161 1184 1144 1207 914 n.a. 1087 1059

a specified not a b a, b a a, b a, b a, b a a, b a a, b a, b b a

a b a a a a a a a a a a b a a b

[82] [84] [82] [82] [82 [82] [82] [82] [82] [82] [82] [82] [87] [82] [82] [86] ]

, , , , , , , ,

[85] [83] [87] [87] [87] [87] [87] [84]

, , , , ,

[83] [84] [84] [84] [85]

, , ,

[85] [85] [85]

, [86]

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Furaneol γ tr 2 B M β γ 2 2 2,4,6 ( ( Pentan ( 2/3 E E E ------enzothiazole Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability - Nonalactone O , , , B Phenylethanol Methoxyphenol Ionone altol 4,5 E Z E romophenole - ctalactone ) ) ) Methylbutanoic acid - - - - 2, 2,4 Nona - T Epoxy

richloroanisole 4 acidoic - -

Decadienal Decadienal - 2,4 - ( E

-

) dienal -

2

-

decenal

Comment citer cedocument: c c metallic plaster rubber caramelized violet coconut rose smoky, ham cork fatty fatty s f sweaty, cheesy atty weaty aramel oconut ACCEPTED MANUSCRIPT - -

like, musty like - like - -

like like

- - -

like like, flowery like

-

like

ACCEPTED MANUSCRIPT

1698 1659 2031 2035 2006 1977 1961 n.a. 1933 1922 1902 1840 1806 1802 1741 1720

1215 870 1070 1363 1382 1071 1227 n.a. 1491 1258 1117 1084 1331 1317 1291 911

a a, b a, not specified a, b a, b b b specified not a, b b a, b a, b b a, b b a

a a a b b b a b a a b a a a a a

[82] [82] [82] [87] [87] [86] [82] [87] [82] [82] [87] [82] [87] [82] [82] [82]

, , , , , , , , , [86] [87] [87] [87] [87] [87] [87] [84] [87]

, , , , , , [83] [84] [84] [83] [85] [83]

, , [85] [85]

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Phenylacetic acid 3 Dodecanoic acid Coumarin I δ ( γ Decanoic acid 2 Sotolone δ 4 γ ( Octanoicacid ndole Z E,Z,Z ------Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability Dodecalactone Decalactone ) Methylindole Aminoacetophenone Ethyloctanoic acid Dodecalactone Decalactone - 6 - γ ) -

- 2,4,7 Dodecenolactone

- Tridecatrienal

Comment citer cedocument: honey f fatty, rancid woodruff jasmin flower fruity, sweet p peach fatty, rancid sweet,honey s c g peach blood musty, plastic aeces avory oconut oat ACCEPTEDeach MANUSCRIPT - like ------like, metallic like, green like, sweet like, fruity like like -

like - like

-

- - like like like

, faecal

ACCEPTED MANUSCRIPT

2115 2050 2539 2484 2465 2465 2456 2431 2380 2345 2276 2200 2196 2190 2190 2137

1581 1277 1248 1262 n.a. 1438 1296 1701 1715 1673 n.a. 1670 1110 1497 n.a. 1470

b b a, b a, b b b b a, b a, b b b a, b a, b a, b a a, b

a a a b b a a a a a a a a a b a

[82] [82] [87] [87] [87] [82] [82] [87] [87] [82] [82] [8 [82] [82] [87] [83] 2]

, , , , , , , , , , , ,

[84] [87] [84] [84] [87] [84] [84] [87] [84] [84] [84] [84]

, , , , , , , , , ,

[85] [85] [85] [84] [85] [85] [85] [85] [85] [85]

, [85]

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Hartmann etal. 2013 3) compound 2) 1) 5α 5 3 Vanillin α - Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability [82] a: stira: barsorptiveextraction and headspace Phenylpropanoic acid - - Androst Androst comparison of :

Buettner 2007,

- - 16 16 - - en en - - 3α 3α retention index, odour, and mass spectrum with reference compound, b:

- - one ol [83]

:Spitzer 2013, Comment citer cedocument: u sandalwood beewax vanilla ACCEPTED MANUSCRIPTrine - like, animalic - like -

[84] like, cheese

- : - like

stir bar sorptive extraction, b: solvent assisted flavour evaporation Spitzer Buettner& 2009,

- ACCEPTED MANUSCRIPT like

2600 2548 3082 2906

[85] 1334 1391 2255 2234 : Spitzer: Buettner& 2010

b a, b a, b b

comparison of , [86] : : Bingham et al.2003, retention a b b a

index and odour with reference [87 ] : [82] [87] [84] [82] Loos 2015,

, , , [87] [85] [84]

, , [84] [85] [88]

, [85] : , [88]

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008

Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability Comment citer cedocument: ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability of a of more complex model matrix wouldsuggested be to mim oct butanoic acid. Odorants with arom vegetable oil forvalues 20 milk odorants, referring to thresholds determined in a model matr seldom been applied to the odour of milk. Thus, arewe only aware studyof one providing aroma food to its threshold concentration in the food matrix isfood the calculation itsof A m probably often, however, the authors did not control for the dietof the mothers inthesestudies compounds (VOCs) composition varies 2 the compounds oct suggested to mainly contribute to the overall milk odour vanillin, and three musty unknown compounds savoury extracts attributes individualof in frequent trainings and panel sessions to achievea consensus decision for the odour quality GC dilution and GC A rough estimate of the potentmost odorants inan - enal and dodecanoic acid - - O areO generally named according to a flavour language of the respective lab, whichestablished is 1 ore precise ore method to estimate t - en - . - like 3

T 3 contributes to he fishy smelling ( - one and one ( [92] - hydroxy - O .

(aroma extract dilution analysis Amongstselected the odorants, t

- inter in general

ACCEPTED MANUSCRIPT1 E - ) en - - ACCEPTED MANUSCRIPT odorants. 4,5 4,5

the - - individually 3 Comment citer cedocument: - - - epoxy dimethyl one, one, 2/3 hadhighest the flavour dilution factors repor “ Z aroma value ) , both , both aon quan - hept - In 2010, Buettner and colleagues started a ted ( E a values approaching 1 - - ) - 4 , and this methylbutanoic acid, methional, vanillin, ( - 2(5H) herelative contribution of an odorant to the overall aroma a of dec varia - enal, the metallic smelling (

- ” 2 - bility , defined as - furanone, thehoney enal.

titative and qualitative level has also been notic

had (see below).

For future determination aromaof values : AEDA

the highest flavour dilution factors and he compound only with anaro odour [91] the ratio of the odorant’s concentration inthe ; [85]

[74] .

(or, in some samples, exceeding 1) extract So far, the aroma value

ic the release fromof odorants the milk . ). However, i

- Odour sensations perceived dur like phenylacetic ed regarding E can be ) [83] - 4,5 . - epoxy T n anothersample of milk,

achieved via step hus [66, 86, 89, 90] ppl ,

- volatile organic the E ying ( ix containing 4% ) E - )

4,5 acid, the vanilla - milk ma value> 1

dec concept AEDA - epoxy - 2 , odour odour

- which enal, the

. to

Most - ,

- might be

wise has very ( the use

milk E

were ) -

dec ing was

- like -

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability variation in is milk interest of from a chemical point of view, butalso relevant with regard to a variation in milk parity factors overallThe 3.2 scientific challengeto besolved f by (e.g., evidence differenton o Still, newborns mightperceive milk odour indifferent a way than adults For do. instance, there is studies. lactation, outcome theof analyses, e.g.,sampling the account quantitativ activityodour values. odorants remain still to be identified, and others to be quantified and evaluated in terms theirof orthonasal few odorantshave so far been determined to in occur structural and perceptual terms. In linewith the overall odour of milk being lowintensity,of only a In sum, overall aroma needs to be confirmed reconstitutionvia and omission experiments ( matrix.

Factors influencing the odou [26]

[101

(reviewed by Further, sincethe aroma valuehas some limitations (e.g.,

GC .

Available studies lackoften information about ). Determining theodorants that are importantmost for theneonates thus remains a or - - e occurrence of aroma compounds and their releasefrom the matrix detection by adults O/MS experimentsallowed 103] composition the diet of the mother. This information should be

, daytime odour ACCEPTED MANUSCRIPT [98, 99] Thereby , however,are scarce. ACCEPTED MANUSCRIPT lfactory sensitivity neonatesof to certain odorants as compared to adults

of of milk Comment citer cedocument: [46, 104] ),

, theimpact of the macronutrient composition of milk theon . including

T varies r of milk o fully , and maternal exercise ( utureresearch. during the

to characterizethe odorant composition of milk

maternal infantileor illness

identify and quantify milk odorants method and Understandingmolecular the principles of aroma

feed

[95 milk inconcentrations that

experimental details which may influence the time, tim - 97] e.g.,

and is systematically [105 [93] ing

[100] influenced by various other - of milkcollection along ), an), odorant’simpact to the 107] , maternalage, BMI, ). Studies

which are reported in future shouldtaken be into

are sufficient for e.g.,

on ,

certain parallel

diverse in [94] ).

and

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability octen compounds and acids with increased flavou fresh samples and which however, pronounced decanoic acid, targeted intensities, including “rancid” and “sweaty” attributes overall intensity performed by metallic fresh human milk is of samples stored profileand odorant senso storage constituents(see nutritive mother’ banking or commonIt is 3 relatesmainly to potential modulating effect of this variation neonatal on behav . 2. 1 Storage - ry attributes of milk

3 was not milk , enabling the - , s s milkis not available insufficient amounts , i.e., milk that has one,(

value odorants an intense metallic, fishy, rancid weet to supply at 4°C and rancid and

and convenient

Z [85, 92] , the and detected , )

- fatty, rating 1,5 odour [108, 109]

samples revealedthe that concen

dodecanoic acid

impact storageof and prior milktreatments - ACCEPTED MANUSCRIPTcomposition octadien the mother’s own nursli suckling ) fishy, - very

ACCEPTED MANUSCRIPT of milk or fruit

19 sweaty changesdueto with Comment citer cedocument:

°C [110]

not been not stored but

stored at

low intensity to an adult’s nose , and

to for reviews)for - storageat 4 practice to store before milk feeding infants

3 y, sour,y, to experience odour

compare , as shown by - odour one,( cooked

of

m increased during storage at possibly4°C, generating the more increased, -

ilk samples 19 E descriptions and

) - storage, -

milk 4,5 the resulting °C .

°C

Ideal earthy and , Spitzer & Buettner r dilution factors in the - trations of (

epoxy the original milk aroma. [85, 112] -

ng when B like

ue sweaty off ly, t evaluated immediately aftersampling

and certain attributes wererated with higher lactational stage,

upon storageat ttner ( [111] attributes determinedaroma by profile analyses . W - he sens . (

E To ) . hen stored for - odour she

[92] 2 Characterizing the odorant and colleagues . After ensure E - ) dec - -

is absent 2 odour developed ory quality . C

[ -

21] nonenal, γ enal, ( to oncurrent quantitativeanalyses of 13 1 the quality storedof milkin terms of

iour. th [85]

and and hasbeen described as has been investi

e odour different conditions. They first and E

, sample

, 3 detected several carbonyl or nurslingsor for whom own The evidence Z

3

However, , of milkshould not days of storageat 4°C, the Z who who maternal diet or more months - ) nonalactone,octanoic acid, - 2,4,7

released by with it

stored at determined thearoma

in human samples milk - tridecatrienal, ( storage can gated ,it be

available so far composition of .

-

19°C . fresh milk

for several The odourThe of for milk at

be altered by - , notably 1 19

hay affectthe °C, E - , like, Z

)

- ,

- Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability e.g.,age the ofinfants the testingat PFCCS) with PA < 36 weeks (n= 8). The significantwas aon whole group level and inthegroup with > PA 36 weeks, but in not thesubgroup stress cues (e.g., crying)were observed during feeding of the stored milk at Preterm Feeding CuesCoding System (PFCCS cha milk (PA): 36.9 weeks) ( feeding thawed (stored milk at infants newborn important parameter for food acceptance ininfants further report that thesame quantities wereconsumed both with Howevermilks. behaviour performed was stored at didindicate not a discriminative (poly)unsaturated fatty acids the before milk at decalactone,γ concentrations of hexanal, odorants infresh and stored samples, demonstrating a statistically significantincrease in the acid, and 3 2,4 stored at - - 19 nges nonadienal, and ( s . H

°C ,

did notdiffer between owever,in thesubgroup with PA Hungal. et ( , preventingconclus a [90] > standard2 deviations from thebaseline - 4 19°C - - phenylpropanoicacid 7°C for less than hours) 24 . The d The -

nonalactone,γ

( storage bearing theoff . On a whole group level, the physiological measuresdid notdi [114] ACCEPTED MANUSCRIPT evelopment of the metallic,fishy E , ACCEPTED MANUSCRIPT Z , indicatingthe that off )

- assessed heartrate, oxygen saturation, and Comment citer cedocument: 2,4

by the respectiveby the mother without specifying responsecriteria. octanal,

- [112] decadienal -

the two mi dodecalactone, octanoic acid and decano ion fromreported the -

- feeding timeand efficacy odour 13°C for a minimum and of 6 a maximum of 98 and days) “fresh” milk feeding behaviour . This observation was corroborated by quanti .

1 According to Spitzerand Buettner , and the coder was not blind to the nature ofstimulus. the - octen ), in), comparison with

to pr , as well as decanoic acid, dodecanoicacid, phenylacetic

> 36> weeks(n 10), = thawed milkelicited heart more rate lks - eterm infants(GA: < 37 weeks, mean postmenstrual age . Again, certain methodological information is missing, 3 ; Lin ; 2005, personal communication in - one,( - odour develops by enzym

) of neonates (n 4)= who were bottle

E [113] than“fresh” the milk.

) off observatio - 2 - - non odour was prevented by heat treatment of , and self , notwas provided for each participating

fresh milk enal, ( n .

- Insimilar a study preterm on E regulation cues (according to , E

feeding behaviour . ) [85] - Yet, rating theof feeding 2,4 ic acid during aticoxidation of

, preliminary experiments - According items to of a nonadienal, δ - 13°C fic ffer . Thisdifference ation ation of 20 targeted , the [114]

between the two

storage infant -

fed when

- ), more The authors

milk age,

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability beclassified colostrum as (before lactogenesis II), transitory and milk, mature milk. changein milkcomposition duringfir the occurs after childbirth and is mirrored by a continuous increase in milk volumeand continuous a mammarygland that occur during pregnancy are referred tolactogenesis as I initiationThe lactationof istwo a 3 responses to thesensory properties storedof milk. limitations possibility discriminative of neonatal behaviour, but with stored milk at (poly)unsatura increase of carbonyl compounds and acidsdue to lipid oxidation, and reflecting the high content of stora storage In sum, 2.3 exception of concentrations of selected odorants did barely differ between fresh and stored samples, with the slightly sweetercompa the fishy, metallic, sweaty rancidor attributes was noticed. However, the stored sample ratedwas as stored milksamples. In contr like, egg established using theattributes fatty, metallic, grassy would affect In another study . 2. , respectively, 2 ge at L actation

different storageconditions affect at 4°C - white

- and patchyreporting. 19°C

( the overall E

and long storage - ted fatty acids inmilk. al stag , like,and fishy, which wereall rated with low intensitie E , for morethan )

higher in the stored samples - Buettn 2,4 -

ACCEPTED19°C for more than MANUSCRIPT - e decadienal,

ACCEPTED MANUSCRIPT red to the fresh sample.

odour or odorant composition human of milk er and colleagues Comment citer cedocument: ast toast the samples stored at 2 at

months Indeed, the field stilla lacks thorough - γ stageprocess. The morphological and intracellular changesin the - 80°C had - dodecalactone, Newborns

2 st daysst postpartum led to an intense metallic, fishy off months.

[89] the no no or only influenceminor theon aroma

[89] odour investigated whether storage

Yet, “sweet” is animpreciseattribute. might thus be exposed to this off

P .

reliminaryfeeding experiments and need corroboration due to methodological

of of milk - green, rancid, sweaty, butter

δ - - 19 decalactone,

in a different manner. °C [115]

(see above) .

Accordingly, . s both in thefresh and the

The aroma profile was

investigat beingfactor a 1.5, , no - odour, resulting from an for 24 months

[60] significantincrease in breastsecretions can - ion of . odour odour when fed

Lactogenesis II - Whereasshort It point towards the like, sweet, hay

can profile The

neonatal

be

2.1 at

of of milk ,

- and 80

°C - ,

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability concentrations corresponding and unidentified two compounds women, n smelling woodru benzothiazole, the plaster pyrroline,green, the earthy smelling 2 that had not samples also occur in maturemilk samples. detect odorants via odour quality and retention indices on two transitional milk samples obtained < elucidated relativeimpact of with higherconcentrations incolostrum. al. samples, higher methylamineconcent and oxygen been reported in milkbefore C changesduring odour chan activity closureor ofparacellul the hypothesised that o odoranto foundwas to beof major olfactory importancein allsamples. olostrum hasbeen subjected to [71] ed odorants are listed inTable and1, it becomes evident that many odorants

detected ff

the flavour dilution factors of 5α - like smelling coumarin, thelily .

gesupon weaning - - Hence, w containing heterocycles androst

been described inmature milk transitional samples. milk [117] initiation of amino acid conjugates of h

the lactational stag

- ACCEPTED MANUSCRIPT 16

e and thedifferent fatty acid composition detected recently ACCEPTED MANUSCRIPT - en Comment citer cedocument: - - likesmelling 3α lactation. , including fatty acids, aldehydes,lactones, alcohols, amines, terpenes, , -

ol a few studies are available investigating

applied odorous compounds . GC Flavour dilution factors varied e mightinfluence were ar pathway

- [1, 67, 116] 50 h50 and > MS

rations weredetected in colostrum - (

ethyl E GC higher 2 -

, - analyses, S like Z Yet, theseanalyses include did not olfactometry bromophenol,coconut the uch differences , - Z O

Yet, t uman sweatodorants in colostrum andsamples, milk before - ) , faecal

3,5 - to 2,4,7 . in the Whereas w

65 h . By directly comparing colostrum and mature milk - dichloromethane distillates of dimethylpyrazine, the his stil - demonstrating thepresence of odorants . These were the roasty smelling 2

tridecatrienal,well as as β

odorantcomposition

smelling post on the overall odour colostrumof remain colo l needsto be confirmed GC strum samples compared to partum, respectively may enot are awareof any addressing study cap

indole,and thesandalwood in

be explained by thehigher carotenoid illaries differentof polarity

colostrum, transitional and mature between individual samples. - like smelling γ

whether theodour of milk rubber , dueto differentsecretory

Nonetheless, [63] - , . - ionone,( colostrum and likesmelling identifying Similarly

for

those odorants - octalactone,the of the - acetyl the E for certain , Hartmann et ) - - , and

like 2

the colostrum [87] - - that had nonenal, 1

Thus, - s

. the

to be The Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability research theon chemical basesunderlying the aroma transfer into milk, studies haveb mayreflected be in whether neonates can perceive such differences, and to which extent the differentodour qualities carrots according to drug transfer Odorants are most often lipophilic and of low molecular weight and can thus 3.2 mightadditionally affect aroma release. Thereby,needs it to bekept inmind that colostrum differs from milkin its overall composit supposed odorants hasbeen d andquantitative that changesoccur during lactogenesis II,notwithstanding that t hypothesis that the concentration of odorantsin breastsecretions depends on thelactational stage, stage influences the odour profile I newborns transitional acid precursors mightbe a common principle berelated to its precursor’s concentration. tridecatrienal beingproduct a of autoxidation of this acid polyunsaturated fatty acids including arachidonic acid milk t cant be concluded that weare only at the beginning understandingof in which way the lactational .3 [118, 119] Maternal exposure to and intakeof odorants [126]

. quantitative difference

or or m , the maternal diet [122] 1,8 een excellently reviewed . Indeed, colostrum ature - cineol ,

infants’ ACCEPTEDbe expected to passinto Indeed,milk. t MANUSCRIPT etected colostrum inboth and milk. milk milk result ACCEPTED MANUSCRIPT

[127] Comment citer cedocument: discriminative behaviour , , e.g. after consumption garlic of and after smoking ing s inodorant concentrations quantificationvia experiments s

from days 1 of colostrumof and milk.

in distinct aroma profiles

[131, 132]

A utoxidation products that are specificto certain fatty of - 5

different fatty acid compositions colostrum of and

is known to contain high [128, 129] .

H ence, during breastfeeding [118 Future research should addressthe [75] Th only only recentmore literature - heodour quality of milkcan vary 121] . e availablee evidencesupports the Mennella and colleagues

, its concentration canexpected be to that mightbe differentiated by the [123] . Thecompound ( , alcohol

is

contents presented [123 , [124] from - 125, 129, 130] he majority of milk E

, , van our knowledgeour on Z of ,

Z here.

, together with investigated ) - illa 2,4 ,7

[125] ion which . - . These ,

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability They investigatedThey Individual cineole metabolites, whereas milkcontained thenon well as between cineole cineole, epoxy severalto metabolites cineole (onecapsule) eucalyptus (Soledum cineole (eucalyptol), which is the major constituent of In another study, µg/kg, 38 and 90 µg/kg, and 53 and 99 µg/kg, respectively metabolites, with maximum concentrations of AMS, A ingestion of 10 gramson led a to garlic characteristicgarlic odo natural aroma profile [134] concentrations ranged between sulfide(AMS), allyl methyl sulfoxide (AMSO)and allyl methyl sulfone(AMSO O samples was detected 2 to hours3 after consumption 3of graw garlic principles. demonstrated by A

/ common food MS, threeMS, garlic . - WhereasAMS has 1,8 [136] α ®

3 -

odorants were cineole, 2 ) - Inmore a recent - , like odour hydroxy is . Thereby, the metaboliteprofiles of 1,8

transferred with characteristicflavour differentbody fluids

Kirsch Mennella & the transfer of - derived compounds were detected in the sampl milk -

ACCEPTED- MANUSCRIPT 1,8 oxo .

of garlicof (a combination differentof odo occurred

This odour was traced back bearing ACCEPTED MANUSCRIPT

- rant(AMS) was and colleagues cineo

-

a garlic 1,8 Comment citer cedocument: also into milk.

study - cineole, 3

le, 4 Beauchamp consumed by mothersparticipating inastudy by an eucalyptus in milksampled - 1 li d

by Scheffleret al. - ke AMSOodour, and AMSO and 4 µg/kg, 30 and 145 µg/kg, and 4 - hydroxy carvone, Aroma profileanalyses indicated [136

- -

[127] oxo transferred and - [123]

- 139] is garlic - 1,8 1,8 cabbage l -

- investigated whether the eucalyptus like odour menthol, - - . Thus, urinemainly contained glucuronides of 1,8 cineole, 7 , yet withoutunravelling the underlying molecular ar cineole,

ound twohours after ingestion of 100 not only , andtransfer the itsof odour

in amounts [133] - - - like odour of milk and excretion theof same cineole differed both between individuals as conj

MSO, andMSO, AMSO2 ranging between and 1.7 2.0 a non trans ,

α namely 2,3 - , the garlic 2 hydroxy

ugated aglycone metabolites. [135] to to - hydroxy - - prescription pharmaceutical product anetholeand 3 the 2 rants)was notreplicated in

are perceivableto adults .

molecule 1,8 -

1,8 odourless. Thus, t - - -

1,8 dehydro and cabbage

- that

cine by the mothers 9 - es, namely cineole,

and 200 µg/kg, respectively the highest intensity of the ole andole 9 2 - ) - methylbutyl acetate . 1,8 - Themaximum cineole itself butalso Hausner into milk β - cineole, - - 2 like odour inmilk

like smelling 1,8 allyl methyl - - hydroxy . hough the hydroxy

Similarly, . Using GC

et al. mg 1,8 milk α has been 2,3 - - 1,8

1,8 [140] , one ------.

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability remains toinvestigated be comprehens either profile theof breastfeeding mother’s diet is In t sum, concentrations consumptiontea by means of main terpenes inthe tea samples, nursing well. marker odorants (e.g., saturate mothers in postpartum) fish supplementation oil project odo profileand composition of fish oil were experiments long on In explanations suchpoor as solubility henceprior to thefirst samplingin point that study). Otherwise,the authors raise authors provide anecdotal evidencethat transfer into milk might occur very fastfor this odorant(and transferred into showedplateau a pattern severalover hours. c into after milk co oncentration maxima

milk other other rants w

Otherwise, not transferred or

samples

(fennel . studies heevidence

However,the diet of the control group’s mothers isnot specified in thatstudy, and the e ive . re then screened in for milksamples after the women took partin a defined long N

- o statisticalo

did not significantly increase , anise obtained from motherssupplemented understand

milk Denzer no no odour ACCEPTED MANUSCRIPT nsumption of 100 - ,

-

term fish supplementation oil available sofar caraway) leastat not inamo ACCEPTED MANUSCRIPT in

et et al.

metabolised milkwere determined Comment citer cedocument:

transfer in

ly whether the ing

significant

[142] GC

of d aldehydesand ketones) can beexpected to occur in other foods as tea into mothers’ milk

(starting from the 16

- the metabolicfate of odorantsin thelactating body MS selected target terpeneswere qu

mg of each odo studied in milk fat hydrolysisor inthe stomach. is to

. in combination with stableisotope dilution assays.

F restricted to specificfoods and

milk milk higher determined urther studies would be important to metabolism of odorants unts above thedetection limit

the transferof odorants from commerciall partly transferred was in milkafter tea consumption.

In contrast

concentrations of the for

detected rantin capsules.

in lactating women d by sensory analyses and - th . After carvoneand

with fish oil week gestationweek of , t . Sandgruberet al. he ester 3

identification and quanti in

to milk in general, , trans compared to a control group of After around twohours, antified in milkbefore and after

- marker odorant methylbutyl acetate wa

suggests that

. In astep, first of theof meth , certain molecules being - anethole , until 4

and [141] GC gainmore a

- hencealso O th ,

/MS

fur month month performed whereas od

the aroma s ther possible fic .

. w the odour y y available . The marker

For instance,it Yet,the ation ation of the ere T he terpene

their evident l - menthol s not - term

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability 4 the aim elucidatingof the role of milk odour in mother detection of available this reason,For is it unclear whetherstorage field odour differentpattern enzymaticof processesand substrates. suggested to be reflectedquantitative by being odour theoretical interestbut aromaof changes depend We infantand henceinduces thebehavioural effects summaris these,of aor combination of odorants, conveys the chemosensory percept of milkodour to the noses Fromabove the 3.3 adapting models derived from transfer of odorants into milkcanpredicted be from therespective chemical structures, to which extent the milk/plasma concentration ratios o transfer into milk . Future directions

Conclusions further

still

metabolism but nonetheless comprisesplethora a of odorants.It is of of milk further

lacksa studies

deduce that thearoma of such , e.g., weaning physical or activity, have not yet been addressed varies according to maternal

-

systematic

cited mostly addressed diet ,

changes

is shapedgenetic by and exogenous aroma transferfrom theplasma.

ACCEPTED MANUSCRIPT studies, ACCEPTED MANUSCRIPT may Comment citer cedocument: s

by

effort on also the nursling

it becomes evident that storage research drugon transfer

beused to optimise to in

milkis altered by cold storage

vestigatethe detection of milk

temperatureand duration. - or epigeneticor factors. Furth induced . differencesin aroma composition, possiblydue to a

This needs beto considered when planning with research

dietary aroma intake, the - induced changesare noticed by the infant. T milk odour stor - milk is of overall low odour intensity r infantinteraction.

temporal quantitativeor aspects of [143] Other factors po age conditions of ed infirst the part of this review

alterations and

still unknown .

This er, iter, mightbe worth to evaluate L , actational stage has and that odour supposed molecular mechanism finding

tential

expressed milk. M

pointtowards the changesby the infan whetheran odorant out

in depth

the extent and nature is not only of ly influencing the .

Further, t

e.g. via

also he . for adult

the

ilk been t. he

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability 4 e.g., thosetarge beodour fluids, e.g. learned in amnioticfluid and recognized in milk odour? dietary aroma intake? And, once learned, can thesame signature odour berecognized in ( tempting to assumea signature odour specificto the respective mother discriminatebetween the odour what makes candidate for conveying acid conjugates occurring in human sweat, and having been detected in is milk, onepotential what makes Finally, environment,specifically the Such research might also indicatethe origin of certain individuals, in or the context lactationalof stage or dynamic changes duringbreastfeeding a session. would also contr basicour understanding of milk odour, e.g. calculationvia of additional odour activity values, but composition of the milk, notablymost the fa however, westill lack quantitative data on the occurrenceof odorants inrelation to the overall Certainly, the 4 the field. toaim elaborate evidentIt is that severa see see .2 .1 Deciphering Elucidating the starting point neonatalof r [146] two

determined by themethods ) . But ifso,

aspects related to the communicative valueof milk odour human human firststeps havebeen taken

ting molecules of higher molecular weight milk odorantcomposition ibuteto characterize differencesin further

ACCEPTEDmilk odour specifi milk odour specific MANUSCRIPT

will this signature beodour ACCEPTED MANUSCRIPT l aspects information specific to humans on selected areas researchof that wedeem to be of major importance to Comment citer cedocument: diet, fromor

s of researchof on milk odour

of of their own mother’s milkand

c described above

to a to humans

to elucidate the odorant composition of milk. Despite this,

andbehaviourally its active metabolism human t content esponse disturbedalterations by of milk odour dueto ?

mother Theodour odorant

(see (see s odour ). , or do we need complementary techniques,

to milk

[145] ?

[144] deserve closerattention. ?

- composition that occur between As reported above,infants behaviourally activecompound , but there mightbe others. -

generating principle beyond amino odour ) . This would not contribute only to of of

And finally, can suchsignature a another mother’s is It milk.

remain to beelucidated principles

as anunderlying principle s

(e.g., from the

W e therefore

other body Second, .

First,

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability Bourgogne, and the Centre National de laRechercheScientifique. Womenfor in Research an Sponsorship Funding: question of neonates react to milk odour isstill missing. familiar formula orientation and longer mouthing towards juice movementsin responseto unfamiliar bottle milk environments evident, supporting the hypothesis of transnatal chemo labour room) whom experiencewas accomplished by Marlier et al. in1997 having investigated neonatal behaviour towards the odour of milkbefore the firstbreastfeeding ethical of sucking and intake, and ha the mother beh besupposed to occur right birth.after Thus, maternal odours may elicitand modulateinfantile postpartum In view of the crucial need the of response aviours and states ina way that favours successful birth transition and [20] - fed neonates. T 6 and practical were

. Even This work fundedwas by - s how infantdyad. [3, 147]

– , no discriminative behaviour towards familiar amnioticfluid and familiar colostrum was present right birth,at isitor the result of

without Förderung von Frauen in Forschung und Lehre (FFL) after [11] the odour of

(see

ACCEPTED MANUSCRIPT , anadaptivebehavioural interaction between the mother andneonate the can . reasons, question this hasbeen addressed very seldom. 3

However, thisis hus, as outlined above, any ACCEPTED MANUSCRIPT days of [148, 149] As outlined above Comment citer cedocument: ve d Teaching) breastfeeding experience

a soothing effect on infantsexperiencing milk fo

rmula feeding, newborn to gain accessto colostrum, bestduring firsthour the ,

is involved in the Free State Bavariaof for review

and familiar , indirect

the French National Research Agency, theRegional Council of the odour of , the odour

Therefore, futureexperiments needed are to answerthe s

1 evidence. ). Further,i -

neonates furthershow day very

milkcompared with fo - old bottle

(and just 3 exposed to mother’sbreast in the early s

[7] some kind of unfamiliar compared milk to of sensory continuity Direct evidence howon newly

. Indouble a ndirect colostrum and

adaptive maternal

(Bavarian Equal Opportunities - fed neonates evinced longer mouthing evidence comes from studies with

–

Promoting Equal Opportunities postnatal - choicetest with distress or ed milk rmula, water, and orange

a preferential head between the amniotic and that - O

do infantile interactions. learning? Due to neof rare the studies conserves energy in

indeed promote pain. the odour of the - 9 Yet, born neonate is this s, of set

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability UniversitätErlangen Acknowledgements:

ACCEPTED MANUSCRIPT -

Nürnberg, Germany, for inspiring discussions and comments theon manuscript. The authorsThe would liketo thank ConstanzeSharapa, Friedrich ACCEPTED MANUSCRIPT Comment citer cedocument:

- Alexander -

Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability 10.1002/(SICI)1098 an odor experienced postnatally in the feeding context. Dev. Psychobiol. 1998, 33:133 [8] Marli 10.1016/S0764 newborn. Initial pattern and postnatal plasticity. C R Acad SciSerIII Sci Vie. 1997, 320:999 [7] Marlier, Schaal,L., B., Soussignan,Orientation R. responses to biological odours inhuman the différentielle du mode d'alimentation? [6] Marlier, Schaal,L., B. Familiarité et discrimination olfactive chez le nouveau 8624.1998.tb06232.x. fluids: Atest of [5] Marlier, Schaal,L., B., Soussignan,Neonatal R. responsivenessto the odor of amnioticand lacteal Found. Symp. 1975, 33:103 [4] Macfarlane,A. Olfaction inthedevelopment socialof preferencesin human the neonate. Ciba 97:289 [3] Schaal, B.,Al Aïn, S.Chemical signals 'selected for' newborns in mammals. Anim. Behav. 2014, about maternal state, mammae, and milk.Vitamins and Hormones: Pheromones 2010. p. 83 [2] Schaal, B. Mammary odor cues and pheromones: mammalian infa New York: Springer;2008. p. 325 breastfeeding interactions. In:HurstJL, Beynon RJ, Roberts SC, Wyatt TD, eds.Chem Signals Vertebr. scentas a organ: Exocrinestructures, secret [1] Schaal, B., Doucet, S.,Soussignan,Rietdorf, R., M., Weibchen, G.,Francke, W.human The breast References - 99. doi:99. 10.1016/j.anbehav.2014. er, Schaal,L., B., Soussignan,Bottle R.

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- 0. -

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1:47 - 61.

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nt - directed communication - 23. 23. doi: 10.1111/j.1467 - né: influence - 45. doi: - 1005. doi: - 136.

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J., Webb, William

- guided responses to colostrum and (and milk

R., Cutforth, T., Ngai, J., Stowers, LearnedL. - Etego, S.,Owusu - 2.

- Agyei, S.,Kirkwood, B. R. n mice. Curr. Biol. 2012, 006, 117:e380 Handbook - e6. Version postprint and detection bynewborns. Physiology andBehavior, 199,88-99. ,DOI:10.1016/j.physbeh.2018.11.008 Loos, H. M.,Reger,D., Schaal,B.(2019). Theodour ofhumanmilk: Itschemical variability communicativefunction of human milk odour. Issuesthat deserve attention i Many odour Human neonates detectand respond to human milk odourphysiological by and behavioural means. Human milk affectsodour mother - active molecules havebeen identified in human milk. ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT Comment citer cedocument: n future research are highlighted, especially those concerning the - infant

- interaction during breastfeeding.