Amniotic Fluid Composition Responds to Changes in Maternal ...

Nutrient
Metabolism
Amniotic Fluid Composition Responds to Changes in
Maternal Dietary Carbohydrate and is Related to
Metabolic Status in Term Fetal Rats1»2
KRISTINE G. KOSKI3 AND MARJORIE A. FERGUSSON4
School of Dietetics and Human Hutrition, McGill University,
Ste. Anne de Bellevue, PQ, H9X ICO, Canada
ABSTRACT The objective of this study was twofold: 1)
to determine whether amniotic fluid composition re
sponded to differences in the level or source (glucose vs.
fructose) of maternal dietary carbohydrate, and 2) to
establish whether any dietary-induced changes in am
niotic fluid composition correlated with matemal or fetal
metabolic status at term. Pregnant rat dams were fed
graded levels (0, 4, 12 and 60%) of glucose or fructose
in a triglyceride-based diet (Experiment 1) or isoenergetic
low carbohydrate diets having 4% glucose equiva
lents as glucose, fructose, or lipid-grycerol (Experiment
2) throughout pregnancy. Amniotic fluid and maternal
and fetal samples were collected at term (d 21). Results
demonstrated a significant increase in amniotic fluid
glucose and a significant decrease in amniotic fluid uric
acid as the level of carbohydrate increased in the ma
ternal diet. Pearson correlation coefficients showed am
niotic fluid glucose to be positively associated with ma
ternal and fetal liver giycogen and fetal weight; amniotic
fluid uric acid and urea nitrogen were negatively corre
lated with these same measures. Regression analysis
indicated that amniotic fluid glucose was predictive of
fetal body weight and fetal liver giycogen at term. The
findings show that amniotic fluid can be modified by
maternal diet and suggest that composition of amniotic
fluid might be used as an accessible nutritional indicator
of carbohydrate status in the developing fetus. J. Nutr.
122: 385-392, 1992.
INDEXING KEY WORDS:
•carbohydrate •amniotic fluid
•glucose •uric acid •rats
retardation followed (1, 6, 7). The belief has been that
this compromised growth arose from lack of nutrients
normally provided by amniotic fluid.
Glucose is considered the major metabolic fuel
utilized by the developing fetus (8). Lowered amniotic
fluid glucose has been associated with intrauterine
growth retardation and has been produced during
prolonged fasting and starvation (9, 10). However, no
study has examined whether amniotic fluid glucose
responds to changes in the level of glucose in the
maternal diet.
The purpose of the present study was to determine
whether the level or source of maternal dietary carbo
hydrate, an essential nutrient during pregnancy (11),
would produce changes in amniotic fluid composi
tion. A second aspect of the study was to establish
whether any diet-induced changes in amniotic fluid
glucose, láclate,uric acid or urea—putative indicators
of fetal maturity and metabolic distress (12-22)—
were correlated with the previously reported maternal
or fetal metabolites (23) and could be predictive of the
poor reproductive outcome that generally accom
panies the feeding of carbohydrate-restricted diets
during pregnancy (11, 23-26).
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Amniotic fluid may play an important role in fetal
nutrition (1). It is well known that the fetus swallows
amniotic fluid and that the fetus in humans and in
several animal species has the ability to digest and
absorb carbohydrate and protein (2-5). The possibility
that the ingested amniotic fluid represents a source of
nutrition for normal fetal growth and development
has been inferred from studies in which fetal swal
lowing was prevented and substantial growth
Resented at the 75th Annual Meeting of the Federation of
American Societies for Experimental Biology, April 1991, Atlanta,
GA [Koski, K. G. S. Fergusson, M. A. (1991) Amniotic fluid com
position responds to changes in maternal dietary carbohydrate and
predicts term fetal metabolic status in rats. FASEB J. 5: A917 (abs.)].
^The financial support of the Natural Sciences and Engineering
Research Council of Canada (NSERC A3623) is gratefully acknowl
edged.
To whom correspondence should
4M. A. Fergusson was the recipient
be addressed.
of the Natural Sciences and
Engineering Council Postgraduate Research Scholarship.
0022-3166/92 $3.00 ©1992 American Institute of Nutrition. Received 26 November 1990. Accepted 10 July 1991.
385

386 KOSKI AND FERGUSSON
TABLE 1
Composition of triglyceride-based and fatty acid-based carbohydrate-restricted diets1
Ingredient
CarbohydrateSoybean
oilOleic
acidCelluloseCaseinVitamin
Carbohydrate-restricted
Control diet2 Triglyceride-based3 Fatty acid-based4
diets
wt438.06—38.9411.01.25.50.341.017.36(4.15)1234.91—34.0911.
g dry
mixMineral
mixMethionineSodium
bicarbonateMetabolizable
kf/g(kcal/g)6016—511.01.25.50.341.017.36(4.15)039.64—41.3611.01.25.50.341.017.36(4.15)g/100
energy,
1The detailed composition was described previously (23).
2The control diet represents the 60% carbohydrate diet containing either glucose or fructose at this level.
3The carbohydrate-restricted triglyceride-based diets contain 0% carbohydrate (0%C-TG) and 4 or 12% glucose or fructose.
''The fatty acid based diets are designated by either 4%G-FA or 4%F-FA, with the G or F designation referring to the type of carbohydrate
(glucose or fructose) added to these diets.
MATERIALS
AND METHODS
Experimental design. The study formed part of a
larger investigation that compared the potential of
fructose to replace an isoenergetic amount of glucose
in the diet of pregnant rats. The maternal and fetal
variables were previously reported (23). In this paper
the changes in amniotic fluid composition following
changes in maternal dietary carbohydrate are
described. This investigation was similar in design
and rationale to the previously reported study (23)
and, like the earlier study, was divided into two ex
periments. In Experiment 1, graded levels (0, 4, 12 and
60%) of two carbohydrates (fructose or glucose) were
fed to pregnant rat dams throughout pregnancy, using
triglyceride-based diets. In Experiment 2, to de
termine whether the form of carbohydrate was im
portant at low levels of intake, three different diets
with similar levels of "glucose equivalents" were
compared. These diets were as follows: 1}4% glucose,
fatty acid-based (4% G-FA); 2} 4% fructose, fatty
acid-based (4% F-FA); and 3) 0% carbohydrate,
triglyceride-based diets (0% C-TG). These diets con
tained 4% glucose, 4% fructose or 4% carbohydrate
precursor as lipid-glycerol (soybean oil), respectively.
The term "glucose equivalent" as used in this
paper refers to the potential glucose yield from either
dietary carbohydrate directly or the glycerol moiety of
the intact triglycéride(soybean oil). Glucose equiva
lents that could be derived from the glycerol moiety
are calculated based on the observation that the
glycerol moiety is 10% by weight of the intact trigly
cérideand lipid is 90-95% digestible. Thus, the fatty
acid-based diets containing glucose and fructose had,
in addition to the 4% glucose equivalent from either
the glucose or fructose, an additional 0.5% glucose
equivalent as lipid-glycerol from the 5% soybean oil,
due to the previously established dietary requirement
for this level of intact triglycéridein the diet of
pregnant rats (26, 27).
Diet formulation. The general composition of the
diets is described in Table 1; the detailed composition
was described previously (23). Each diet was calcu
lated to contain 17.36 kj (4.15 kcal) of metabolizable
energy per gram dry matter, which is the energy
requirement for pregnant rat dams (27).
The rationale for the formulation of the basal
carbohydrate-free diet for pregnant rat dams was
described previously (26). These carbohydrate-free
diets were based on the concept that glucose must be
the first limiting nutrient, and any measurable change
following the addition of incremental amounts of
glucose or its equivalents must be attributable specif
ically to the addition of glucose or glucose equiva
lents and not to significant alterations in any other
dietary component. The metabolizable energy of
fructose is considered to be identical to that of
glucose (23). hi these diets, protein is minimally ade
quate to supply the levels of protein, nitrogen and
essential amino acids and not in excess to provide
supplementary gluconeogenic precursors. The major
dietary component, therefore, is lipid, either as intact
triglycérideor food grade fatty acids, the latter having
the minimally adequate level of intact triglycéride
(5%) previously described as an essential dietary com
ponent of fatty acid-formulated diets (26). Supple
ments of glucose or fructose were added to the basal
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carbohydrate-free diet to replace an equal weight of an
isoenergetic amount of oleic acid or triglycérideplus a
complementary amount of cellulose to compensate
for the weight of the supplement.
Experimental animals and chemical analysis. Bred
female Sprague-Dawley rats (180-200 g) (Charles
River Canada, St. Constant, PQ) were used in all
experiments. Upon arrival (d 0 or 1 of pregnancy), the
pregnant rats were housed in individual suspended
wire-screen cages and were fed the experimental diet,
to which they were randomly assigned, in a
temperature-controlled room (20"C); fluorescent
lighting was provided automatically for a period of 12
h daily from 0700 to 1900 h. Water and experimental
diets were fed ad libitum. Individual body weights
and food intake were measured every second or third
day. Dams were delivered of fetuses by caesarean
section on d 21 of gestation. All dams were killed in a
post-absorptive (fed) state under anesthesia with
ketamine-HCl (Rogarsetic, Roqar/STB Inc., Montréal,
PQ) injected at a level of 30 mg/kg body wt into the
jugular region to avoid anesthetizing the fetuses. Ma
ternal blood was withdrawn by cardiac puncture. All
procedures were conducted in conformance with the
guidelines for experimental procedures set forth by
the local animal care committee of McGill University
and by the Canadian Council on Animal Care (28).
Plasma was subsequently isolated by centrifugation
and stored at -20*C until analyzed as previously
described (23). Immediately following cardiac punc
ture, the intact uterus was removed. Amniotic fluid
was drawn from each amniotic sac into a 4-cc tuber
culin syringe until 1-2 mL were collected in an Eppendorf
tube on ice. The pooled amniotic fluid was
subsequently stored at -20°Cuntil analyzed using an
Abbott VP-Super System (Irving, TX) with Sigma Kits
(Sigma Chemical, St. Louis, MO) for glucose, lactate,
uric acid and urea nitrogen as described by the
manufacturer. The number of analyses performed on
AMNIOTIC FLUID AND MATERNAL DIET 387
each amniotic fluid constituent varied according to
the quantity of amniotic fluid obtained as a result of
different pup and litter sizes. In general, the practice
was to perform the analyses in the following order:
glucose, lactic acid, uric acid and urea, until the am
niotic fluid sample was exhausted. Maternal and fetal
livers were removed, freeze-clamped using liquid air
and stored at -80'C until analyzed for glycogen as
described previously (23).
Statistical analysis. All statistical procedures were
analyzed using SAS (29). A two-way ANOVA was
conducted on data from Experiment 1 using level and
source of carbohydrate as main effects. The amniotic
fluid values in the zero carbohydrate group were ran
domly divided into two groups so that the design was
a 4 x 2 factorial initially; however, all 0% values were
regrouped and treated as one in the presentation of
the results, because the absence of either carbohy
drate in these treatment groups resulted in the com
position of the diets being equal. If there were no
statistically significant differences between the
glucose and fructose groups, the data for these two
groups were combined and the statistical analysis
using linear contrasts was performed and reported in
the results section for the pooled data (glu + fra). The
following comparisons using linear contrasts were
done for Experiment 1: 0 vs. 4%, 4 vs. 12%, 12 vs.
60% for amniotic fluid glucose, uric acid and urea,
and 0 vs. 60% was added for lactic acid only. In
Experiment 2, a one-way ANOVA was performed
using data from rats fed the three glucose equivalent
diets. Correlations were done using pooled fetal data
rather than the individual pup data, because only one
amniotic fluid sample had been obtained per litter.
Multiple linear regression analyses were performed
using all of the amniotic fluid constituents as inde
pendent variables in the model and each fetal variable
(fetal weight, glucose, lactate, uric acid or liver
glycogen) as the dependent variable.
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TABLE 2
Effect of low carbohydrate, 4% glucose equivalent diets during pregnancy on amniotic fluid composition at term (Experiment 2)1
Amniotic fluid
constituentsGlucose
|4%G-FA)0.44
glucose (4%)Fructose(4%F-FA)mmol/L
equivalents
(0%C-TG)0.44
Uric acid
Lactate
Urea nitrogenGlucose
± 0.05 (8)
47.5 ±11.9 (7)
4.44 ± 0.04 (8)
4.43 ± 0.60 (7)Dietary
0.33 ± 0.05 (9)
83.27 ±11.9 (9)
4.77 ± 0.22 (8)
4.17 ± 0.79 (9)Lipid-Glycerol
± 0.05 (9)
89.22 ±11.9 (5)
5.11 ± 0.44 (8)
5.36 ± 0.89 (6)
Values are means ±SEM.Number in parentheses equals number of dams from which amniotic fluid samples were obtained. There were no
significant differences for any value among the three dietary treatment groups using one-way ANOVA. 4% G-FA - 4% glucose, fatty
acid-based diet; 4% F-FA - 4% fructose, fatty acid-based diet; 0% C-TG - 0% carbohydrate, triglyceride-based diet.

388 KOSKI AND FERGUSSON
TABLE 3
Effect of graded levels of maternal dietary ¡focóseor fructose during pregnancy on amniotic fluid composition at term
(Experiment
Dietarycarbohydrate0%4%Level
of Carbohydrate12%60%
GlucoseFructoseGlu+fru30.44
±0.44
±0.110.11a(9)(9)0.72
\unol/L"GlucoseFructoseGlu+fru389
Glucose, mmol/L*
±0.66
±0.69
±0.160.11(9)(1010.12ab
(19)1.00 (18)Uric
acid,
±89
±30
±47
±3030«(5)(5)59
±24612b(8)(7)(15)18 (14)Láclate,
mmol/L'"GlucoseFructoseGlu+fru3GlucoseFructoseGlu+fru35.10
±5.10
±5.4
±5.4
(8)0.90.9a(6)16)4.22
±0.44(8)0.44^
±5.00
±4.60
±3.3
±0.89
±0.94
±0.110.160.1 lb(9)(7)(16)1.89
±24
±23
±5.00
±4.88
±nitrogen,
mmol/L^3.5
±6612C(6)(5)(11)24
±1.83 (8)0.16
±1.85 (10)O.llc
±0.11
±18
±17
±5.22
±5.43
±3.0
(7)6
(7)12C
±6
(9)0.22
(10)0.22b
(19)0.3
±3.9
±3.2
±2.8 (8)0.2
±3.6
±3.4
±2.9 (10)0.3b
±0.330.330.22a0.30.70.3b(8)(10)(18)Urea(8)(9)(17)4.66
±0.220.220.22a0.20.30.4b(8)(7)(15)(8)(6)(14)5.77
±0.11 (18)
'Values are means ±SEM.Number in parentheses equals number of dams from which amniotic fluid samples were obtained. Means for
each amniotic fluid constituent having different letter superscripts differ significantly (P < 0.05) using linear contrasts.
^Significance of main effects from two-way ANOVA: for none of the measurements was the source of the carbohydrate or the interaction
of source x level of carbohydrate significant. Based on significance of main effects by ANOVA, level of carbohydrate was significant at: *P <
0.0001, **P < 0.01, *P < 0.005.
3Glu+fru represents the pooled means for glucose and fructose combined (see statistical analysis section).
RESULTS
Analysis of variance. The effect of low carbohy
drate 4% glucose equivalent diets during pregnancy
(Experiment 2) on amniotic fluid glucose, lactate, uric
acid and urea nitrogen is summarized in Table 2. The
effects of graded levels of maternal dietary glucose or
fructose on these same amniotic fluid constituents
(Experiment 1) are summarized in Table 3. There
were no significant differences (Experiment 2, Table
2) for any amniotic fluid constituent among rats fed
these three 4% glucose-equivalent diets (4% F-FA,
4% G-FA, 0% C-TG), indicating that the source of
carbohydrate (glucose or fructose) or carbohydrate
precursor (lipid-glycerol) was not important. How
ever, the results showed that all amniotic fluid con
stituents were significantly affected by the level of
carbohydrate in the maternal diet (Experiment 1,
Table 3). As the amount of either glucose or fructose
increased in the maternal diet, there was a significant
rise in amniotic fluid glucose concentration from a
low of 0.44 mmol/L when there was only lipidglycerol
as a carbohydrate precursor in the maternal
diet to a high of 1.89 mmol/L when 60% glucose or
fructose was supplied in the diet. In contrast, as di
etary glucose or fructose was added to the maternal
diet, amniotic fluid uric acid concentration showed a
statistically significant and progressive decrease be
tween 0, 4 and 12% dietary carbohydrate,- it then
plateaued, because there was no statistically signif
icant difference between the 12 and 60% dietary
treatment groups. Amniotic fluid lactic acid and urea
concentrations were not as sensitive to changes in
maternal dietary carbohydrate. For amniotic fluid
urea nitrogen, there was only a statistically signi
ficant reduction between 0 and 4% dietary carbohy
drate. The 4, 12 and 60% dietary treatment groups did
not differ significantly. The 60% carbohydrate control
group had a significantly higher concentration of
lactic acid in amniotic fluid compared with either the
4 or 12% dietary treatment groups,-however, the con
centration of lactic acid in the amniotic fluid for the
low carbohydrate (0% C-TG) group was not signifi
cantly different from that of the 60% control group or
those of the 4 and 12% dietary treatment groups,
making it difficult to use amniotic fluid lactic acid
concentration predictably to discriminate between
low and high carbohydrate dietary treatments.
Correlations. The probabilities of the Pearson cor
relation coefficients for comparisons of amniotic fluid
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AMNIOTIC FLUID AND MATERNAL DIET 389
glucose, lactic and uric acids, and urea nitrogen with
maternal or fetal plasma glucose, lactic and uric acids,
urea nitrogen, and liver glycogen and fetal weight are
summarized in Table 4.
Amniotic fluid glucose was significantly and posi
tively correlated with maternal plasma lactic acid and
maternal liver glycogen as well as fetal weight and
fetal liver glycogen. There was a weak association (P -
0.07) between amniotic fluid glucose and fetal plasma
glucose. In contrast, amniotic fluid glucose demon
strated a significant negative correlation with ma
ternal and fetal plasma uric acid concentrations and
maternal plasma urea nitrogen.
Amniotic fluid lactic acid was significantly and
positively correlated with only maternal liver
glycogen.
Amniotic fluid uric acid and amniotic fluid urea
nitrogen were correlated significantly with one an
other. Hence, when either one was compared with
maternal and fetal metabolites, the pattern of signif
icant relationships was similar. Both amniotic fluid
Amniotic fluidLactic
acidUric
acidUrea
nitrogenMaternalPlasma
TABLE 4
uric acid and urea nitrogen were significantly posi
tively correlated with maternal plasma urea nitrogen
and significantly negatively correlated with maternal
liver glycogen. Fetal weight, plasma glucose and liver
glycogen were significantly and negatively correlated
with amniotic fluid uric acid and urea nitrogen. The
results showed that fetal plasma uric acid but not
maternal plasma uric acid was significantly related to
amniotic fluid uric acid.
Multiple regressions. The regression analyses of
the various amniotic fluid constituents against the
dependent variables of fetal body weight, fetal plasma
glucose, lactic and uric acids, and fetal liver glycogen
are summarized in Table 5. Certain amniotic fluid
constituents were significantly associated with fetal
(d 21) body weight and term fetal liver glycogen.
Amniotic fluid glucose was positively associated with
fetal weight and fetal liver glycogen at term, whereas
amniotic fluid uric acid was significantly and neg
atively related to fetal body weight. Amniotic fluid
Pearson correlation coefficients of amniotic fluid with maternal, fetal and amniotic fluid variables1'2
Glucose Lactic acid
Amniotic
fluid
Uñeacid Urea nitrogen
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glucosePlasma
acidPlasma uric
acidPlasma lactic
nitrogenLiver urea
glycogenFetalWeightPlasma
glucosePlasma
acidPlasma uric
acidLiverlactic
glycogen0.062(76)-0.538***(61)-O.260*(72)0.180(65)-0.337**(67)0.476****(75)-O.482****(64)0.777****(53)0.509(78)0.218(69)-0.319**(60)-0.087(73)0.693***
'Number in parenthesis equals number of observations.
2Probability of Pearson correlation coefficient: *P < 0.05,
'P < 0.01, ***P < 0.001, ****P < 0.0001.

390 KOSKI AND FERGUSSON
Amniotic fluid
constituentsGlucose
Lactate
Uric acid
Urea nitrogen
f-value
Adjusted multiple
InterceptFetal
TABLE 5
Amniotic fluid constituents as predictors of fetal metabolic status using multiple regression1
weight0.023
(0.007)**
-0.010 (0.010)
-0.415 (0.190)*
0.027 (0.027)
4.77**
R2 0.34
4.21 (0.48)Fetal
metabolitesGlucose0.027
plasma
(0.405)
0.677 (0.568)
(0.277)
-0.432 (0.388)
-14.93 (9.88) -0.337 (6.754)
-2.47 (1.40) 0.294 (0.963)
1.71
1.08
0.09
0.001
59.85 (25.41)Lactate-0.223 66.26 (17.36)***Uric
acid-0.007
(0.006)
0.002 (0.008)
0.429 (0.146)**
0.020 (0.020)
4.54**
0.330
0.890 (0.375)*Liver
glycogen1.188
(0.198)****
-0.192 (0.277)
-9.144 (4.814)
-0.795 (0.686)
14.36****
0.65
26.28 (12.38)*
'Values are parameter estimates (SEM).The multiple regression was performed on 36 observations. Probability: *P < 0.05, **P < 0.01, ***P
< 0.001, ****P < 0.0001. Units were based on concentrations in mg/100 mL for maternal and fetal plasma and ammode fluid values and mg/g
wet wt for liver glycogen.
glucose seemed to be predictive of fetal liver glycogen
and explained 65% of its variability.
DISCUSSION
Even though amniotic fluid is thought to be in
volved in fetal nutrition, virtually no study to date
has investigated the role of maternal diet on amniotic
fluid composition. This is the first study to show that
amniotic fluid glucose, urea, uric acid and lactate
concentrations respond to changes in the level of
maternal dietary carbohydrate, which is an essential
nutrient for fetal growth and development and
perinatal survival (11, 23-26). Again, as with the pre
vious report comparing the effects of graded levels of
maternal dietary glucose vs. fructose on fetal growth
and development (23), we concluded that it is the
level, not the source, of carbohydrate that influences
the outcome. In general, the results from this study
showed that as maternal dietary carbohydrate (either
as glucose or fructose) increased in the maternal diet,
there was a significant increase in amniotic fluid
glucose and a significant decrease in amniotic fluid
uric acid. The correlation coefficients showed that the
higher amniotic fluid glucose was associated with
increased maternal liver glycogen, fetal weight and
fetal liver glycogen deposition, whereas higher am
niotic fluid uric acid and urea were correlated with
lower fetal weight, fetal plasma glucose, and maternal
and fetal liver glycogen. These data indicate that
measurements of these amniotic fluid constituents
might predict fetal growth and metabolic maturity.
We suggest that a decreased intake of maternal di
etary carbohydrate during pregnancy leads to lower
maternal and fetal glycogen reserves and a higher
metabolic requirement for gluconeogenesis, hence the
fall in plasma glucose and the rise in plasma urea and
uric acid levels. The fact that these long-term meta
bolic adaptations to reduced dietary carbohydrate are
mirrored in the amniotic fluid is a novel finding.
Previous reports in the literature described am
niotic fluid constituents as indicators of fetal distress,
noting in separate studies that low glucose (18, 19)
and high lactate (12, 13), urea (15-17) and uric acid
(14, 20) are associated with hypoxia and poor
perinatal prognosis. In the present study, we mea
sured all variables simultaneously and found signifi
cantly lower glucose, and significantly higher uric
acid and urea nitrogen in the amniotic fluid from
dams fed the 0% carbohydrate triglyceride-based diets
when compared with the other dietary treatment
groups. In Hams fed 0% carbohydrate, amniotic fluid
lactate was comparable and amniotic fluid glucose
was lower than in controls, which contrasted with
other carbohydrate-restricted dietary treatment
groups (4 and 12%) that had lower amniotic fluid
glucose and lactate when compared with control
dams. This observation is similar to those in previous
reports of studies involving non-diabetic humans (16,
30), in which low amniotic fluid glucose concentra
tions in conjunction with high concentrations of
plasma lactate were associated with fetal distress and
neonatal asphyxia. The first paper (23) in this series
reported an increased résorptionand in utero death
rate and fewer live fetuses at term in the dams, which
(in the present study) were reported with low am
niotic fluid glucose accompanied by high amniotic
fluid uric and lactic acids and urea nitrogen following
the restriction of maternal dietary carbohydrate. It is
known from other studies that offspring fed a low
carbohydrate diet experience a significantly higher in
utero (11, 23, 26) and postnatal (11, 23-25) death rate,
but prognostic indicators of this diet-induced
perinatal death have not been established. The appli
cation of the changes in amniotic fluid composition
to these mortality studies suggests that hypoxia,
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AMNIOnC FLUID AND MATERNAL DIET 391
arising from disturbances in carbohydrate metabo
lism, may be related to the perinatal mortality when
pregnant rats or dogs (11, 23-26) are fed carbohydraterestricted
diets. These results suggest that amniotic
fluid constituents may have prognostic significance
for fetal carbohydrate homeostasis, but with differing
sensitivities. Amniotic fluid glucose and uric acid
responded with significant measurable changes over
the entire range of maternal dietary carbohydrate
intake (0-60%). Amniotic fluid urea and lactic acid
were less sensitive, showing only significantly greater
levels in rats fed the low (0%) or high (60%) carbohy
drate diets, respectively. Therefore, we conclude, as
others have, that amniotic fluid glucose seems to be a
better guide to the condition of the fetus than am
niotic fluid lactic acid (12) and that amniotic fluid
uric acid is a better guide than amniotic fluid urea
nitrogen in this diet-induced model of fetal and ne
onatal distress, in which carbohydrate-restricted diets
in the dams produced increased perinatal mortality
(11, 23-26).
The combined results from this and the previous
study that used these same dietary conditions (23)
suggest that the intake of dietary carbohydrate by rat
dams increased the deposition of maternal liver
glycogen, which in turn was associated with increased
concentrations of amniotic fluid glucose and fetal
liver glycogen. Other models of fetal distress have not
used diet in the experimental design and these results
suggest it is a factor. Reductions of maternal dietary
carbohydrate were associated with reductions in am
niotic fluid glucose and fetal liver glycogen at d 21,
but not in significant disturbances to the plasma
glucose concentrations in either the fetal or maternal
systems, suggesting [as noted by others (30, 31)] that
the latter were not as sensitive as amniotic fluid
glucose or fetal liver glycogen to long-term perturba
tions in glucose homeostasis during pregnancy.
Therefore, we suggest that the fetal swallowing of
amniotic fluid glucose assumes a critical role in pro
viding glucose to the near-term fetus in pregnant rats.
We further suggest that amniotic fluid glucose may be
an accurate mirror of fetal glycogen reserves and the
progressive decrease in amniotic fluid glucose, which
is widely observed with advancing age (9, 22, 32),
occurs because the fetal swallowing of amniotic fluid
near term supplies some of the glucose precursor for
the increasingly rapid rise in glycogen reserves in the
fetal liver as parturition approaches (33).
LITERATURE
CITED
1. Mulvihill, S. J., Stone, M. M., Debas, H. T. & Fronkalsrud, E.
W. (1985) The role of amniotic fluid in fetal nutrition. J.
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