Studies in human lactation: milk volume and nutrient composition during weaning and lactogenesis13 Margaret Ronald

C Neville, Jonathan C Allen, Philip P Keller, Valerie Lutes, Jean Rasbach,

ABSTRACI’

Concentrations

nutrients (birth

and

major

to 8 d) and

Postpartum trations

signalled was

secretion milk

rates

sodium,

ofthe

paracellular

2 to 4 postpartum,

weaning

during

during

days

of copious

with

feed

Temporal

changes

in the

glucose weaning

to maintain

concentration

milk

of other

and magnesium, were women. Differences

secretion.

milk

components,

not different between the

and composition during lactogenesis volume is differently regulated in the

J Clin Nuir

except

later

during

heifers

place (7) showed

lactogenesis,

stage

in women

as well

and two

paper

to refer to changes

ofthe

infant

Am

lactogenesis

lactogenesis,

suckling

concluding

that

the main before cretory

“A

ingredients and

after

activity

published in 1935, Widdows et al (1) and postnatal secretions of the breast

comparison

ofthe

of the

fluid secreted

parturition

shows

is involved

and

that

not

relative

proportions

of

by the mammary

gland

a true

in se-

merely

difference

a difference

in con-

centration.” Subsequent studies of lactogenesis in women have not been sufficiently detailed to allow conclusions to be drawn about the physiological basis of this difference in secretory activity,

although

studies

in dairy

animals

provide

substantial

components

to the lumen

ofthe

mammary

alveoli

concentrations (2of the mammary

alveolar

milk

cells

the relative changes

themselves

results

in the concentration study reported here contributions in milk

Am J C/in Nuir

volume 1991;54:8l-92.

in increased

secretion

of certain milk components was undertaken primarily ofthese

and

two

processes

composition

that

Printed

in USA.

and

(6). to assess

to the temporal occur

to oh-

milk

pro-

secretion

early

begins

studies

in a limited

be termed lactogenesis, secretion after parturition this

be used

(9),

in mammary stable

distinction for

without

stage I, being appears

simplicity’s

sake

qualification

secretion volume

in this

from

the birth

is achieved,

usually

(6). Initiation

by the infant

have

10, 12-15)

although

to milk volume stances, including lactose (17). Decreases

postpartum

process

intervals. well

their

time

in milk

volume

occur

courses

whenever

in

on

secretion

ifmilk

removal

changes

during

producing has been

a fall

prolactin

not depend

declines

have only been published trace elements (16), milk

to the infant regularly, (18, 19). Abrupt weaning

by

ofmilk

Profound

documented

detailed

does

the rate

day postpartum

been

period

of maintained

1 1) although

at regular

composition

the

presence

ofthe

(10,

or fourth

practiced

is offered weaning

in

in the

in milk

lactogenesis and

(1,

the relation

for certain subproteins (14), and supplemental

food

partial

or complete

found

to be accom-

during

© 1991 American

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I From the Departments of Physiology and Preventive Medicine Biometrics, University of Colorado School of Medicine, Denver, the Department of Food Science, North Carolina State University,

and and Ra-

leigh.

reflected

in changes in sodium, chloride, and lactose 5). 2) An increase in the synthetic activities changes The

able

those

sup-

port for the hypothesis that two separate physiological events are involved: 1) closure of the junctional complexes between mammary alveolar cells prevents direct access of extracellular space

with

as the copious

as in cows

is initiated

after the third is not

we were

However,

milk

a relatively

progesterone

concentrations

Introduction

some

gradual

5.

plasma

wean-

defined

II. Although

will

until

Lactogenesis

Human milk, lactation, pathway, milk composition

study, weaning

parturition.

that

to hold

suggest

Because

initiated

leading to a proposal by Hartmann (8) of the capacity of the mammary gland to

termed term

same

during

often after

in weaning and nonrelation of milk volweaning periods.

of the

secrete milk during pregnancy with the onset of copious milk

the

women.

lactogenesis

changes

is most

taking

day

In an elegant paper examined the antenatal

phases

way during pregnancy, that the development

1991;54:8l-92.

KEY WORDS ing, paracellular

during

lactogenesis.

Lactogenesis

and a demilk proobserved than one

in breast-feeding

studied

composition

served

milk

free phosphate, glucose, and calcium concentrations crease in pH. During weaning, significant changes in tein, lactose, chloride, and sodium concentrations were only when milk volume fell below 400 mL/d; more necessary

increases

compare

duction

per day was

period

are reported.

concen-

Seacat,

postpartum

subjects

pathway

by significant

Joy

of the

chloride

initiation

early

in citrate,

ume that

accompanied

and

of macro-

E Casey, Neifert

lactogenesis

during

(> 6 mo postpartum)

in lactose,

closure

days

secretion

and in human

late lactation

changes

From

1-2.

ions

C Archer, Clare and Marianne

the Society

2 Supported by NIH contract HD-2-280l and NIH grant HD-l9507 (MCN) and grant RR 69 from the General Clinical Research Centers Program ofthe Division of Research Resources, University of Colorado Health Sciences Center. 3 Address reprints requests to MC Neville, Department of Physiology, University of Colorado School of Medicine, Denver, CO 80262. Received April 19, 1990. Accepted for publication September 26, 1990.

for Clinical

Nutrition

81

82

NEVILLE

panied

by substantial

changes

in the concentration

ofsome

milk

components (20), whereas gradual weaning had a much smaller effect on milk composition (2 1, 22). In none of the previous studies of weaning were enough subjects studied to differentiate clearly

between

the

effect

of duration

oflactation

and

the effect

of decreasing milk volume. In this paper we report the results of detailed measurements of changes in milk composition during lactogenesis in 1 1 fully breast-feeding women, correlating our findings with both time postpartum and milk volume. Milk composition during full lactation in these same women is described in the accompanying paper (5). Milk volumes throughout lactation in these women were reported previously (23) as were trace element concentrations in these milk samples (16). Subjects

and

methods

Subject selection, sample collection, were fully described in previous reports jects were nonsmoking, primiparous, women who had previously breast-fed planned to breast-feed for 1 y. Milk by weighing

the infant.

Milk

and

analytical

(5, 23, 24).

methods Briefly,

volumes

were

was measured

measured

Data analysis dividual,

repeated it was

measurements necessary

that

were longitudinal

made

in the same methods

Results

Lactogenesis

in-

(days 1-8 postpartum)

Figure 1 (top) shows the lipid and protein concentrations in the mammary secretion during lactogenesis. Lipid increased immediately after birth from ‘-2% to ‘-3.5% and then continued to increase

irregularly

for

the

first

week.

Protein

on

the

other

hand

started to decline on day 1, reaching a steady level of’-- 1.5% (wt:vol) by day 4. When these concentrations were multiplied

by the milk volume, the protein and lipid secretion rates were obtained (Fig 1, bottom). The lipid secretion rate rose rapidly between 36 and 96 h, reaching ‘-30 g/d, equivalent to 1130 kJ/d

(270

kcal/d).

The

total

protein

secretion

rate

appeared

to

remain constant at -‘-‘4 g/d until 48 h postpartum, then rose to twice this level by 96 h. The average milk volume (Fig 2) increased rapidly and more or less linearly from 36 to 96 h postpartum and then abruptly off.

The

concentrations

of citrate,

free

phosphate,

and

glucose

mirrored milk volume secretion, increasing rapidly between 36 and 96 h postpartum. The concentrations of lactose, potassium, sodium, chloride, calcium,

on small

samples taken from each breast 3 mm into the feed. Samples were divided and stored at -70 #{176}C until analysis by methods that were detailed earlier (5, 24).

Because

AL

leveled

sub-

middle-class Caucasian at least one infant and

composition

ET

and

magnesium

(Fig

2) changed

rapidly

immediately

after birth, stabilizing before 96 h. Lactose concentration, example, reached a steady value ‘ 60 h postpartum whereas its secretion rate stabilized 36 h later. The vertical line in Figure 2 corresponds to the point in time where secretion leveled off. The rise in lactose concentration sponded most closely to the major decreases in sodium chloride concentrations occurring before 60 h postpartum.

(Fig

for 2)

dotted

lactose correand

As

of data

analysis be used. The essence of such patterns for individuals be determined for statistical purposes (25). This was Lactogenesis: time dependence. The and secretion rate for each individual

methods is that temporal before pooling the data done as follows. data for milk composition were plotted for each cornponent and carefully scrutinized. Because the temporal patterns were similar for all milk components in all individuals, the data were averaged across individuals for designated time ranges and plotted. Lactogenesis: volume dependence. The data for each individual were plotted as a function ofvolume as shown in the right-hand graphs of Appendix Figures A1-A3. Where a linear model provided the best overall fit to the data, true for all milk components except sodium, lactose, chloride, and protein, the data for each individual were subjected to linear-regression analysis against volume and the statistical coefficients were pooled across subjects. Where the data were nonlinear, the data were pooled across subjects at designated time intervals and a mean line was plotted. Late lactation. time dependence. The data for the weaning and nonweaning women were plotted separately for all subjects (Fig Al-A3, charts in the two left-hand columns). Where the individual data fit a linear mode, linear-regression analysis against time was performed and the coefficients were pooled to obtain mean statistical indexes. The data for sodium, chloride, lactose, and protein did not fit this model but did show a consistent pattern for individuals. They were therefore pooled across women at designated time intervals and a mean line was plotted. Late lactation: volume dependence. Only the data for the weaning women were analyzed. The data were analyzed as for volume dependence during lactogenesis and plotted in the third column of graphs, Figures A1-A3.

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-24

0

24

72

Hours

120

Post

Par turn

FIG 1. Lipid () and protein (#{149}) concentrations (top) and secretion rates (bottom) during lactogenesis. Secretion rate was calculated from the concentration for that time point multiplied by the volume secretion rate for the corresponding time interval for each woman. The data were then averaged across individuals. ± SD, except when the SD was smaller than the diameter of the symbol.

LACTOGENESIS

AND

WEANING

IN

83

WOMEN

V 0

E E 0

-J 0

E E

.

0 0

4 C

0

0 C

a) C) C

0 C-)

-?0

0

40

80

20

60

200

Hours FIG 2. Concentrations () and SDs as described

means

discussed below, of tight junctions Urea

and

somewhat birth;

pH

creatinine

most

other

pH

and

showed

linear-regression tose, in

all

sodium, subjects

concentrations

changes

over

ionized

calcium

components

were

the relation

shown chloride, (Appendix

very

from

approximately 1 and

protein Fig

Al,

of closure small

of lactogenesis

fell significantly decline

whenever and

period

soon

days

and

possible.

The

to milk

volume

graphs

D,

H,

major relation

of lacP),

with

Downloaded from https://academic.oup.com/ajcn/article-abstract/54/1/81/4691104 by guest on 23 February 2018

that esis

80

20

60

200

during

lactogenesis.

Calculations

and

changes in concentration occurring as volume increased 300 mL and slow or no change as volume increased above

of the

was nonlinear L, and

rapid to

ofthe

by using

relation

milk components

after

of the milk volume

40

urn

500 mL. the major

stable.

2 to milk

0

Part

(Fig

4 to 8 when

of the concentration

in Figures

analysis

showed

the

an additional

We examined components

rates (#{149}) ofseveral

these changes are most likely the result between mammary epithelial cells.

erratic

3). Both

and secretion in Figure 1.

-40 Post

This

decreases are not

creases. The sonably

pattern

changes increase

between in sodium, simply the

concentration fit to volume

D, H, L, P, and

was expected

in these

A3,

components

from

the observation

occur

‘

that

1 d in advance

in milk

volume

(Fig

2). The

milk

volume

and

concentration

nonlinearity shows

chloride, and protein during lactogenresult of dilution as milk secretion inof other milk with a linear

components could be reamodel (Appendix Figs A2,

D, H, L, P. T). Data

from

each

woman

84

NEVILLE

were

fit by using

were

pooled

free

phosphate,

analysis

1 ). The

and

concentrations

potassium,

and

the

calcium

were

reflect

changes

milk

synthesis.

creased.

in metabolic pH

Lipid,

showed no rate oftheir be

significant secretion

associated

significantly

magnesium,

ionized

calcium,

with

changes

in

with urea,

and

creatinine

composition

during

and

postpartum. with

supplemented

their

milk

volumes

tended

with

the

feed

diets

with

frequency

period

solid

slopes

by the

over

of heavy

lines

this

of the five women whose milk volume the course ofthe study (Fig 5). (The sixth reaching cross

to

a milk the

suggesting maintain

point to be of exclusive

1.6 3.8

infant’s

in the

weaning

denoting

mean

zero

volume

of ‘-400

volume

that

more

significant made from breast-feeding

declined subject

axis than

one

milk these

one

feeding

production.

The and

rates

±

± 0.2

0.59

0.1

±

2.4 ±

0.64

Pt

±0.2 ± ±

0.9 0.57

± 0.04