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Maternal nutrition in early and late pregnancy in relation to placental and fetal growth

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Abstract and Figures

To assess how nutrient intakes of mothers in early and late pregnancy influence placental and fetal growth. Prospective observational study. Princess Anne Maternity Hospital, Southampton. 538 mothers who delivered at term. Placental and birth weights adjusted for the infant's sex and duration of gestation. Mothers who had high carbohydrate intakes in early pregnancy had babies with lower placental and birth weights. Low maternal intakes of dairy and meat protein in late pregnancy were also associated with lower placental and birth weights. Placental weight fell by 49 g(95% confidence interval 16 g to 81 g; P=0.002) for each log g increase in intake of carbohydrate in early pregnancy and by 1.4 g (0.4 g to 2.4 g; P=0.005) for each g decrease in intake of dairy protein in late pregnancy. Birth weight fell by 165 g (49 g to 282 g; P=0.005) for each log g increase in carbohydrate intake in early pregnancy and by 3.1 g (0.3 g to 6.0 g; P=0.03) for each g decrease in meat protein intake in late pregnancy. These associations were independent of the mother's height and body mass index and of strong relations between the mother's birth weight and the placental and birth weights of her offspring. These findings suggest that a high carbohydrate intake in early pregnancy suppresses placental growth, especially if combined with a low dairy protein intake in late pregnancy. Such an effect could have long term consequences for the offspring's risk of cardiovascular disease.
Content may be subject to copyright.
Key
messages
*
Reduced
weight
for
length
(ponderal
index)
at
birth
was
associated
with
a
threefold
increased
risk
of
non-insulin
dependent
diabetes
in
Swedish
men
at
age
60
years
*
There
is
no
evidence
that
reduced
fetal
growth
is
associated
with
impaired
,3
cell
function
at
age
50
years
(as
measured
by
the
insulin
response
to
intravenous
glucose)
*
The
combination
of
thinness
at
birth
and
overweight
in
adult
life
is
associated
with
higher
insulin
concentration
at
1
hour
after
intravenous
glucose,
suggesting
an
effect
on
insulin
resistance
*
Control
of
obesity
in
adult
life
is
likely
to
be
especially
effective
in
reducing
the
risk
of
non-
insulin
dependent
diabetes
in
those
who
were
thin
at
birth
be
especially
effective
in
reducing
the
risk
of
diabetes
in
people
who
were
thin
at
birth.
We
thank
Lena
Nyvall
and
Charlotte
Freiman
for
help
with
tracing
the
birth
records.
Funding:
UK
Medical
Research
Council.
Conflict
of
interest:
None.
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disease.
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Fall
CHD,
Osmond
C,
Phipps
K,
Clark
PMS.
Type
2
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diabetes
mellitus,
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1.
(Accepted
30
November
1995)
Maternal
nutrition
in
early
and
late
pregnancy
in
relation
to
placental
and
fetal
growth
K
Godfrey,
S
Robinson,
DJP
Barker,
C
Osmond,
V
Cox
Medical
Research
Council
Environmental
Epidemiology
Unit
(University
of
Southampton),
Southampton
General
Hospital,
Southampton
S016
6YD
K
Godfrey,
epidemiologist
S
Robinson,
nutritionist
D
J
P
Barker,
director
C
Osmond,
statistician
V
Cox,
computer
analyst
Correspondence
to:
Dr
Godfrey.
BMJ1996;312:410-4
Abstract
Objective-To
assess
how
nutrient
intakes
of
mothers
in
early
and
late
pregnancy
influence
placental
and
fetal
growth.
Design-Prospective
observational
study.
Setting-Princess
Anne
Maternity
Hospital,
Southampton.
Subjects-538
mothers
who
delivered
at
term.
Main
outcome
measures-Placental
and
birth
weights
adjusted
for
the
infant's
sex
and
duration of
gestation.
Results-Mothers
who
had
high
carbohydrate
intakes
in
early
pregnancy
had
babies
with
lower
placental
and
birth
weights.
Low
maternal
intakes
of
dairy
and
meat
protein
in
late
pregnancy
were
also
associated
with
lower
placental
and
birth
weights.
Placental
weight
fell
by
49
g
(95%
confidence
interval
16
g
to
81
g;
P=0002)
for
each
log
g
increase
in
intake
of
carbohydrate
in
early
pregnancy
and
by
1-4
g
(0.4
g
to
2*4
g;
P=0O005)
for
each
g
decrease
in
intake
of
dairy
protein
in
late
pregnancy.
Birth
weight
fell
by
165
g
(49
g
to
282
g;
P=0.005)
for
each
log
g
increase
in
carbohydrate
intake
in
early
pregnancy
and
by
3-1
g
(0.3
g
to
6-0
g;
P=0.03)
for
each
g
decrease
in
meat
protein
intake
in
late
pregnancy.
These
associations
were
independent
of
the
mother's
height
and
body
mass
index
and
of
strong
relations
between
the
mother's
birth
weight
and
the
placental
and
birth
weights
of
her
offspring.
Conclusion-These
findings
suggest
that
a
high
carbohydrate
intake
in
early
pregnancy
suppresses
placental
growth,
especially
if
combined
with
a
low
dairy
protein
intake
in
late
pregnancy.
Such
an
effect
could
have
long
term
consequences
for
the
off-
spring's
risk
of
cardiovascular
disease.
Introduction
Most
low
birthweight
babies
have
a
small
placenta.1
2
The
growth
of
the
placenta
precedes
that
of
the
fetus,
and
surgical
restriction
of
placental
growth
in
sheep
causes
retardation
of
fetal
growth.3
Recent
experi-
mental
studies
in
sheep
have
shown
that
high
nutrient
intakes
in
early
pregnancy
may
also
suppress
placental
growth,
resulting
in
reduced
placental
and
fetal
size.4
In
humans
we
know
little
about
how
nutrient
intakes
in
early
pregnancy
relate
to
placental
and
fetal
size.
Whereas
nutrient
intakes
in
late
pregnancy
have
been
reported
to
have
inconsistent
effects
on
fetal
size,56
their
relation
to
placental
size
is
largely
unknown.
Any
such
effects
may
be
of
long
term
importance
in
view
of
the
associations
between
placental
and
birth
size
and
adult
cardiovascular
disease.27
In
a
prospective
study
we
have
assessed
the
relations
between
the
mother's
410
BMJ
VOLUME
312
17
FEBRUARY
1996
nutrient
intakes
in
early
and
late
pregnancy
and
placental
and
fetal
weight.
Subjects
and
methods
We
approached
all
655
white
women
aged
16
years
or
older
with
singleton
pregnancies
who
registered
under
two
consultants
over
one
year
and
who
attended
the
midwives'
antenatal
booking
clinic
at
the
Princess
Anne
Maternity
Hospital
in
Southampton
at
less
than
17
weeks'
gestation.
Twelve
miscarried
or
had
a
termination
of
pregnancy,
and
seven
delivered
outside
the
district.
Of
the
636
remaining
women,
596
(94%)
agreed
to
participate.
The
mothers
were
visited
at
home
by
a
trained
research
nurse
shortly
after
recruitment
and
again
around
32
weeks'
gestation
(median
duration
of
gestation
15-3
and
32-7
weeks,
respectively).
Mothers
were
asked
about
their
menstrual
and
obstetric
history,
weight
before
pregnancy,
and
smoking
habits
and
were
requested
to
contact
their
parents
and
ascertain
their
own
birth
weight.
Height
was
measured
with
a
stadio-
meter.
Social
class
was
allocated
according
to
the
mother's
current
or
last
occupation.89
Social
class
could
not
be
allocated
for
15
mothers.
In
early
and
late
pregnancy
a
food
frequency
questionnaire
was
administered
that
assessed
the
average
frequency
of
consumption
of
100
foods
or
food
groups
in
the
three
months
preceding
the
visit.
The
nutrient
content'-13
of
a
standard
portion
of
each
food'4
was
multiplied
by
its
reported
frequency
of
use
to
calculate
average
daily
nutrient
intake.
The
early
pregnancy
estimates
have
been
validated
against
those
determined
from
food
diaries
kept
over
four
days.'5
At
birth
the
baby
was
weighed
to
the
nearest
5
g
with
digital
scales.
The
placenta
was
weighed
on
digital
scales
after
trimming
by
stripping
the
amnion
to
the
cord,
cutting
the
chorion
at
the
edge
of
the
placenta,
and
removing
the
cord
flush
with
the
placenta.
Duration
of
gestation
was
estimated
from
menstrual
history
and
ultrasound
scan
data
by
using
a
standard
algorithm.'6
The
study
was
approved
by
the
local
ethics
com-
mittee.
Of
the
596
mothers
recruited,
39
delivered
before
259
days'
(37
weeks')
gestation
and
were
excluded
from
this
analysis
in
view
of
the
strong
dependence
of
birth
weight
on
gestation.
Three
mothers
were
not
visited
in
late
pregnancy
and
placental
weight
was
not
recorded
for
16,
leaving
538
term
pregnancies
with
complete
data
on
nutrition
and
delivery
(85%
of
the
sample
of
636).
Statistical
analysis
was
by
tabulation
of
means
and
paired
t
tests.
Multiple
linear
regression
was
used
to
take
account
of
the
independent
effects
of
separate
variables.
Levels
of
significance
refer
to
regression
analysis
of
continuous
variables.
Nutrient
intakes
were
log
transformed
when
necessary
to
satisfy
assumptions
of
normality.
Results
Table
1
shows
the
characteristics
of
the
538
mothers
and
babies.
Placental
and
birth
weights
rose
with
increasing
gestational
age
at
birth
by
1-6
g/day
and
21
g/day,
respectively,
and
were
higher
in
boys
than
girls.
We
adjusted
both
weights
for
the
baby's
sex
and
duration
of
gestation,
and
subsequent
analyses
use
the
adjusted
values.
Table
2
shows
the
mothers'
median
daily
nutrient
intakes.
Between
early
and
late
pregnancy
a
small
fall
in
carbohydrate
and
rise
in
fat
intakes
resulted
in
a
fall
in
the
proportion
of
energy
derived
from
carbo-
hydrate
(from
49
4%
to
49
0%)
and
a
corresponding
rise
in
that
derived
from
fat
(from
35
7%
to
36-4%).
While
intakes
of
dairy
protein
rose
(from
20-5
g
to
22-3
g/day)
those
of
meat
protein
remained
constant
and
those
of
cereal
protein
fell
(from
34-7
g
to
33-7
g/day).
Intakes
of
iron
and
folate
rose
during
pregnancy
(table
2)
because
of
higher
intakes
from
supplements
in
late
pregnancy.
NUTRIENT
INTAKES
IN
EARLY
PREGNANCY
AND
PLACENTAL
AND
BIRTH
WEIGHTS
Table
3
shows
mean
placental
and
birth
weights
according
to
the
mother's
intakes
of
energy
and
macronutrients.
Placental
and
birth
weights
were
inversely
related
to
energy
intake
in
early
pregnancy,
falling
by
38
g
(95%
confidence
interval
5
g
to
72
g;
P=0
03)
and
134
g
(11
g
to
256
g;
P=0
03),
respec-
tively,
for
each
log
kcal
increase
in
intake.
These
relations
were
largely
dependent
on
an
association
with
carbohydrate
intake,
placental
weight
falling
by
41
g
(10
g
to
73
g;
P=0
01)
and
birth
weight
by
143
g
(28
g
to
258
g;
P=0
01)
for
each
log
g
increase
in
carbo-
hydrate.
Division
of
carbohydrate
into
total
sugars
and
starch
showed
that
the
relations
with
intakes
of
sugars
(P=0
01
and
P=0-02,
respectively)
were
stronger
than
those
with
intakes
of
starch
(P=0
09
and
P=0
1).
Placental
weight
fell
by
27
g
(-2
g
to
56
g;
P=0
07)
and
birth
weight
by
101
g
(-4
g
to
207
g;
P=0-06)
for
each
log
g
increase
in
fat.
Both
were
unrelated
to
the
mother's
intakes
of
protein,
iron,
or
folate
in
early
pregnancy.
After
carbohydrate
intakes
in
early
preg-
nancy
were
taken
into
account
no
more
variance
in
placental
and
birth
weights
was
explained
when
we
also
considered
fat,
protein,
iron,
or
folate
intakes
in
early
pregnancy.
Table
1-Characteristics
of
538
mothers
and
babies
Mothers
No
(%)
primiparous
No
(%)
of
smokers
Social
class:
No
(%)
1,
11
No
(%)
IIIN,
IIIM
No
(%)
IV,
V
Mean
(SD)
height
(m)*
Mean
(SD)
body
mass
index
(kg/M2)
before
pregnancy*
Mean
(SD)
age
(years)
Mean
(SD)
birth
weight
of
mother
(g)t
Babies
(boys;
girls)
Mean
(SD)
placental
weight
(g)
Mean
(SD)
birth
weight
(g)
Mean
(SD)
placental
ratio
(%)
Mean
(SD)
gestation
(days)
285
(53
0)
139
(25-8)
144
(26-8)
283
(52-6)
111
(20-7)
1.63
(0-06)
23.1
(4-4)
26.4
(4-9)
3312
(534)
544
(125);
522
(115)
3527
(496);
3344
(463)
15.4
(2-8);
15.7
(2-9)
281.4
(9-3);
281.2
(9-3)
*Body
mass
index
unknown
for
10
mothers
and
height
for
two
mothers.
tMother's
own
birth
weight
unknown
for
47
mothers.
Table
2-Median
dailyintakes
(lowerand
upper
quartile)
of
the
538
mothers
Intake
Early
pregnancy
Late
pregnancy
Energy
(kcal)
2329
(1882,2789)
2314
(1970,2729)
Carbohydrate
(g)
302.7
(245.7,372-9)
301.9
(254.3,360-6)
Fat
(g)
91.2
(74.2,
112-6)
93.2
(75.8,
111-9)
Protein
(g)
87.2
(69-8,
101-3)
85.7
(72.4,99-8)
Proportion
(%)
kcal
carbohydrate
49.4
(46.2,53-4)
49.0
(46.1,
52-2)
Proportion
(%)
kcal
fat
35.7
(32.5,38-7)
36.4
(33.3,39-1)
Proportion
(%)
kcal
protein
14.7
(13.3,16-5)
14.7
(13-3,16-0)
Total
sugars
(g)
141.7
(109.9,185-0)
151.5
(115.9,
189-1)
Starch
(g)
150.3
(123.2,190-0)
144.3
(116.9,176.9)
Cereal
protein
(g)
34.7
(27.7,
42-0)
33.7
(27-2,40-2)
Meat
protein
(g)
28.1
(19.0,38-3)
28.3
(20.5,37-3)
Dairy
protein
(g)
20.5
(15-2,28-2)
22.3
(16.4,28.9)
Iron
(mg)
15.5
(127,
21-2)
16.8
(13.2,29-6)
Folate
(,g)
315
(252,397)
327
(260,449)
BMJ
VOLUME
312
17
FEBRUARY
1996
411
Table
3-Mean
placental
weight
and
birth
weight
adjusted
for
baby's
sex
and
duration
of
gestation
according
to
mother's
daily
intakes
in
early
and
late
pregnancy
Placental
Birth
Intake
weight
(g)
weight
(g)
No
of
subjects
Early
pregnancy
Energy
(kcal):
-2080
547
3468
180
-2560
535
3446
173
>
2560
520
3412
185
Carbohydrate
(g):
s265
554
3501
181
-340
531
3444
172
>
340
517
3381
185
Fat
(g):
80
542
3456
191
-105
543
3461
165
>
105
517
3409
182
Protein
(g):
76
537
3462
175
-95
536
3427
175
>
95
528
3437
188
Late
pregnancy
Energy
(kcal):
-2080
537
3452
175
-2560
531
3438
182
>2560
534
3436
181
Carbohydrate
(g):
6265
544
3492
170
-340
529
3427
190
>
340
530
3409
178
Fat
(g):
S
80
538
3443
165
-105
530
3432
187
>
105
534
3450
186
Protein
(g):
-76
530
3419
173
-95
534 3453
189
>95
537
3452
176
NUTRIENT
INTAKES
IN
LATE
PREGNANCY
AND
PLACENTAL
AND
BIRTH
WEIGHTS
There
were
no
significant
univariate
relations
between
the
mother's
nutrient
intakes
in
late
preg-
nancy
and
placental
and
birth
weights
(table
3).
After
the
mother's
carbohydrate
intake
in
early
preg-
nancy
was
taken
into
account,
however,
a
low
protein
intake
in
late
pregnancy
was
associated
with
decreased
placental
weight
(P=0-02)
and
birth
weight
(P=0-01).
Though
the
relation
with
placental
weight
reflected
an
association
with
dairy
protein,
there
being
no
associations
with
either
cereal
(P=0-2)
or
meat
protein
(P=0
5),
birth
weight
was
more
closely
related
to
intakes
of
meat
protein
than
those
of
dairy
(P=0-2)
or
cereal
protein
(P=0-2).
Thus
placental
weight
fell
by
49
g
(16
g
to
81
g;
P=0-002)
for
each
log
g
increase
in
carbohydrate
intake
in
early
pregnancy
and
by
1-4
g
(0
4
g
to
2A4
g;
P=0
005)
for
each
g
decrease
in
dairy
protein
intake
in
late
pregnancy
(table
4).
Birth
weight
fell
by
165
g
(49
g
to
282
g;
P=0
005)
for
each
log
g
increase
in
carbohydrate
intake
in
early
pregnancy
and
by
3
1
g
(0
3
g
to
6-0
g;
P=0
03)
for
each
g
decrease
in
meat
protein
intake
in
late
pregnancy
(table
5).
Placental
and
birth
weights
fell
by
15
g
(1
g
to
28
g;
P=0
03)
and
63
g
(14
g
to
112
g;
P=0-01),
respectively,
for
each
log
mg
decrease
in
iron
intake
in
late
pregnancy
and
by
34
g
(11
g
to
57
g;
P=0
004)
and
98
g
(15
g
to
181
g;
P=0-02)
for
each
log
,ug
decrease
in
folate.
These
relations
largely
reflected
associations
with
iron
and
folate
intakes
from
supplements
and
were
independent
of
those
with
dietary
carbohydrate
and
protein
intakes.
MOTHER
S
CHARACTERISTICS
AND
PLACENTAL
AND
BIRTH
WEIGHTS
Primiparous
mothers
had
placentas
that
were
29
g
(8
g
to
49
g;
P=0-006)
lighter
and
babies
that
were
121
g
(48
g
to
195
g;
P=0
001)
lighter
than
those
of
multiparous
mothers.
Placental
and
birth
weights
fell
with
decreasing
maternal
height
(by
336
g/m
(180
g/m
to
492
g/m;
P<0
0001)
and
1541
g/m
(977
g/m
to
2105
gfm;
P<
0'0001),
respectively)
and,
weakly,
with
decreasing
maternal
body
mass
index
(g/weight(kg)/
height(m)2)
before
pregnancy
(by
1-6
g
(-0
7
g
to
3-9
g;
P=0-2)
and
8d1
g
(-0
5
g
to
16-6
g;
P=0
06)).
Though
placental
weight
was
similar
in
mothers
who
smoked
and
did
not
smoke
(difference
1
g
(-24
g
to
22
g;
P=0
9)),
birth
weight
was
146
g
(62
g
to
229
g;
P=0
0007)
lower
in
mothers
who
smoked.
After
maternal
height
and
smoking
were
taken
into
account,
placental
and
birth
weights
were
unrelated
to
maternal
age
and
social
class.
Multiple
regression
analyses
showed
that
the
relations