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