Effects of Fasting During Pregnancy on Maternal andFetal Weight and Body Composition inWell-Nourished and Undernourished Rats1'2

SALLY ANN LEDERMAN ANDPEDRO ROSSO

Institute of Human Nutrition and Department ofPediatrics, College of Physicians and Surgeons,Columbia University, New York, NY 10032

ABSTRACT The effect of a 2-day fast on fetal and maternal weight and composition was determined in ad libitum-fed and food-restricted pregnant and non-pregnant rats. Fasting between days 17 and 19 of gestation resulted in a greaterloss of net maternal body weight in ad libitum-fed pregnant than in nonpreg-nant rats and also a greater loss of body fat. In contrast, food-restricted pregnant rats, also fasted from day 17 to day 19 of gestation, maintained their netbody weight and body fat during the fast as did nonpregnant rats fasted for thesame length of time. Fetal weight was not significantly reduced by fasting inthe ad libitum-fed rats but was reduced by 25% in the previously food-restricted rats. The results demonstrate that prior maternal nutritional statusstrongly influences the effects of fasting on the fetus and that maternal nutrientstores are not mobilized for fetal utilization even when fetal growth is markedlyimpaired. J. Nutr. Ill: 1823-1832, 1981.INDEXING KEY WORDS fasting •body composition •fetal weight

A 50% food restriction during pregnancy has been shown to reduce fetal sizein the rat (1). In spite of the adverse effect on the fetus, changes in maternal netbody weight and body composition arethe same in pregnant and nonpregnantrats during food restriction, indicatingthat the fetus cannot parasitize the tissuesof an undernourished mother to maintain normal growth.

On the other hand when fasted for 2days late in pregnancy, previously well-fed rats have been reported to lose moreweight than do fasted nonpregnant ratsand fetal growth is maintained (2).

The apparent difference between foodrestriction and fasting may be explainedin several ways. For example, adaptationto fasting during pregnancy may be significantly different from adaptations tofood restriction so that fasting results ingreater mobilization of maternal nutrientstores. Also, the greater weight losses observed in fasted pregnant rats may be

caused by changes in body composition,such as a greater loss of water, and maynot signify greater nutrient mobilizationfor fetal use in the pregnant animals.Finally, well-fed animals fasted for 2 daysin late pregnancy may be well above theirprepregnancy weight and may therefore still contain body fat gained in earlypregnancy. This excess weight and fatmay be a prerequisite for increased maternal nutrient mobilization during fasting and for the consequent maintenanceof fetal growth while the mother losesweight. If so, undernourished rats wouldshow a different response to fasting during pregnancy than is shown by well-nourished rats.

The purpose of the present study was

Received for publication 20 February 1981.'Supported in part by NIH grant KO 4 HD 00116 (Research

Career Development Award).1The work reported in this paper was a portion of a Ph.D. disser

tation submitted to Columbia University by S. A. Lederman in 1960.An abstract of part of this work has appeared in Fed. Proc.3S(3):871,1979.

1823

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1824 LEDERMAN AND ROSSO

to determine the changes in fetal and maternal weight and in maternal composition during fasting in well-nourished andundernourished pregnant rats and to compare these to changes in similarly fedgroups of nonpregnant rats to determinewhether maternal nutrient stores are mobilized to aid fetal growth during fastingand whether pre-existing undernutritionalters the effects of fasting on maternalweight and fetal growth.

MATERIALS AND METHODS

Female Sprague-Dawley rats (Holtz-mann Co., Madison, WI) weighing 220-260 g on day 0 (day on which pregnant animals were found to be "spermpositive") were received on day 4 of gesta

tion. The rats were individually caged onarrival and maintained in a temperature-regulated room with a 12-hour light-darkcycle. Water was available at all times.

SOT FASTED

AD LIBITUM

PREGNANTFASTED

NOT FASTED

FOOD RESTRICTED

FASTED

NOT FASTED

AD LIBITUM

NON PREGNANT

FASTED

NOT FASTED

FOOD RESTRICTED

FASTED

17

EXPERIMENTAL DAYS

19

Fig. 1 Timetable shows division of rats into adlibitum-fed and food-restricted groups and then intonot fasted and fasted groups.

All animals were fed a standard laboratory diet ad libitum until day 5 (RQ Ratand Mouse Diet, Zeigler Bros. Inc., Gardners, PA). On day 5,10 pregnant and eightnonpregnant rats were killed and the remaining animals were divided into food-restricted and ad libitum-fed subgroups asshown in figure 1. On day 17, seven ormore rats from each diet group werekilled and the remaining animals in eachof the four groups were distributed between not fasted and fasted subgroups.The not-fasted groups continued on theirprior intake. The fasted groups were totally deprived of food. The remaining animals (7-11 per group) were killed onday 19.

Ad libitum-fed animals were given aweighed amount of excess food andthe uneaten portion was collected andweighed about every 2 days. Food-restricted rats were given their pre-weigheddaily food ration every morning. All food-restricted animals received the sameamount of food, about 50% of the meandaily intake of the ad libitum-fed pregnant group. Food was weighed to thenearest 0.1 g. Animals were weighedto the nearest 0.1 g about twice weeklyand before being killed. Only animalsbearing 10 ±2 fetuses were included inthe pregnant groups.

Animals were killed with an overdoseof chloroform. The maternal .stomach andintestines were excised and discardedafter they had been stripped of visible fatwhich was replaced in the carcass. Inpregnant rats, the fetal sac was severed atthe base of the placenta and weighed. Thefetuses were then freed of the extra-fetaltissues which were discarded. Thecarcass, liver, pooled fetuses and pooledplacentas of each animal were weighedseparately. All retained tissues werefrozen.

Carcass analysis was performed on fouror five animals which were representative of their group with respect to weight.The tail was removed from the carcass,weighed and discarded prior to carcassanalysis. Carcass composition is based onthe carcass weight without the tail.

On the day of analysis, the carcass wascut with shears into several pieces

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and then ground (with fur and bone)through the coarse and fine blades of ameat grinder until it was the consistencyof finely ground meat. Triplicate0.8-2 g samples of the ground carcasswere analyzed for water by drying to constant weight at 95-100°.

For the determination of carcass fat content, duplicate samples of 1-3 g of groundcarcass were weighed into 125-ml Erlen-meyer flasks. The tissue was dispersed in20 ml of vacuum-redistilled hexanes,warmed for 20 minutes or more on a steambath and filtered through sintered glass.The solvent was evaporated offand the fatcontent was determined. Fetal water content was determined by drying four ormore fetuses per dam to constant weightat 95-100°.

Statistical methods. The data wereanalyzed by the two-tailed Students' t-

test (3). Results were considered significantly different if the P value was 0.05or less.

RESULTS

Food intake. Pregnant rats consumedan average of 25 g of food per day duringthe ad libitum feeding period. Intake ofnonpregnant rats averaged 19 g/day.During the restriction period, food-restricted rats consumed 12g per day or 47%of the intake of the ad libitum-fed pregnant group. This represented 62% of theintake of ad libitum-fed nonpregnant rats.

Body weight. Changes in total bodyweight and carcass weight are shown intable 1. The change in net maternalweight from day 5 to day 19 in fasted andnot fasted rats is shown in table 2. Netmaternal weight is the total weight minusthe weight of fetuses and placentas. Sincedifferent animals provided the data fornet weight changes to day 17 and to day19, the changes are not exactly additive.

Ad libitum-fed nonpregnant and pregnant rats gained net weight between days5 and 17, although pregnant rats gained

TABLE 1

Food intake and body weight in ad libitum-fed and food-restricted rats

Total body wt

Day 5 Day 12 Day 17 Day 19 Carcass wtDay

killed

PregnantadlibNonpregnantad

libPregnantrestrictedNonpregnantrestricted247246248253241241239240248252250240240239±2'±5±2±2±3±3±5±3±

1±3±2±2±4±3277289287256258252252256258236240237±

4±3±2±2±3±2±2±3±2±2±5±

3—318

±324±324±_256

±261±253±251

±253±256±223

±228±224

±533231332242——351

±300±——266

±230±266

±241±—226

±203±43223242209

±2245±4a258±2a229±2a(Fasted)205

±2222±2227

±2207±2(Fasted)204

±2*>204±2"189±2"(Fasted)197

±2"200±4"183

±2"(Fasted)101081088677101186851719195171919171919171919

1Mean ±SEM. " Significantly different from corresponding nonpregnant group (P < 0.05). Onlycarcass weights were compared. bSignificantly different from corresponding ad libitum fed group(P < 0.05). Only carcass weights were compared.

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1826 LEDERMAN AND ROSSO

TABLE 2

Weight changes in ad libitum-fed or food-restricted rats fasted for 2 days or not fasted

PregnantadlibNonpregnant

adlibPregnant

restrictedNonpregnant

restrictedMaternal

wtchange beforefasting, days

5-17'+58.2

±2.2»(7)-l-

15.5 ±2.5"

(8)-11.1

±1.7(6)-16.8±

1.8"(8)Gross

wt change,days17-19Not

fasted+26.8

±2.0"

(8)+4.8

±2.5-

(6)+

13.4±1.3(8)-2.2

±1.2'(6)Fasted-23.9

±1.3"

(10)-23.3

*0.9(7)-14.4

±0.6(11)-21.1

±0.5-(8)Net

maternal wt change,days17-191JNot

fastedg+9.0

±1.0"(11)+4.8

±2.5"

(6)-0.6

±0.9(H)-2.2

±1.2(6)Fasted-42.5

î.0.7"

(15)-23.3

±0.9-(7)-24.5

±1.0(15)-21.1

±0.5-(8)Net

maternal wt change,days 5-19'Not

fasted+67.2

±4.6"

(6)+26.8

±4.5"(6)-11.7

±&2(7)-

14.6 ±2.5(6)Fasted+

15.7 ±1.6"

(10)-9.8

±3.2"(7)-35.6

±3.1

(11)-36.6

±1.4(8)

1Weight of fetuses and placentas subtracted in pregnant groups. *Weight change during fasting in pregnant groups = (net weightchange days 5 to 19) - (net weight change days 5 to 17). n for pregnant groups therefore equals the degrees of freedom. Weight change innonpregnant groups = total weight change during fasting. 3 Mean ±SEM; numbers in parentheses indicate the number of animals.•Significantly different from corresponding pregnant group (P < 0.05). b Significantly different from corresponding food-restricted

group (P < 0.05).

substantially more. If they were notfasted, both nonpregnant and pregnantad libitum-fed rats gained additional netweight between days 17 and 19. During2 days of fasting, the nonpregnant grouphad a moderate weight loss and ended thefast below their day 5 weight.

During fasting, ad libitum-fed pregnantrats also lost net weight. After fasting however, their net body weight remainedabove their day 5 weight. Although thepregnant rats lost more net weight whenfasted than the nonpregnant rats, they stillended the fast heavier than the nonpregnant rats did.

The 50% food-restricted nonpregnantrats lost weight during the period of foodrestriction. When fasted 2 days, they lostadditional weight and they ended the fastwell below their day 5 weight.

Food-restricted pregnant rats lost netweight at a rate similar to restricted non-pregnant rats. When fasted between day17 and 19, previously food-restrictedpregnant rats also lost additional weightand, like the nonpregnant restricted rats,ended the fast well below their day 5weight. Thus, restricted pregnant andnonpregnant rats were the same weight atthe end of the fast.

The results indicate that during a 2-dayfast, previously ad libitum-fed pregnant

rats lose more net maternal weight thansimilar nonpregnant rats, as previously reported (2). Previously restricted, fastedpregnant and nonpregnant rats have thesame overall net weight loss.

Body composition. Maternal carcasscomposition was determined on days 5,17and 19 in fasted and not fasted groups,to establish whether fasting affected bodycomposition differently in pregnant ornonpregnant rats and whether prior foodrestriction influenced body compositionchanges during fasting. The body composition data are shown in tables 3 and 4.

Fasting did not significantly changepercent composition in previously well-fed nonpregnant and pregnant rats (table3). However, the absolute amount ofwater, fat and lean dry tissue tended to belower after fasting in previously well-fednonpregnant rats and, in the pregnantgroup maternal carcass water and fat decreased significantly.

Percent lean dry tissue increased andpercent fat decreased significantly duringfasting in previously restricted pregnantrats (table 4). In restricted nonpregnantrats only the decrease in percent carcassfat was statistically significant.

In restricted nonpregnant rats, carcasswater, fat and lean dry tissue were lowerafter fasting but only the decrease in

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TABLE 3

Carcass composition changes during fasting in groups previously ad libitum fed1

Day 19

Day 5 Day 17 Not fasted Fasted

Changeduringfasting

Pregnant ad libWater, %Fat, %Lean dry, %

Water, gFat, gLean dry, g

65.2 ±0.810.9 ±1.323.9 ±0.7

133.1 ±1.622.4 ±2.948.7 ±1.1

65.112.022.9155.528.654.80.50.70.3"1.6*2.0"0.4C64.812.522.7162.431.456.80.70.60.2"1.5»b1.7e1.3C64.910.624.5144.823.854.60.50.90.62.6abc2.5»0.6C

-10.7-4.8-0.2

Nonpregnant adlibWater,%Fat,%Lean

dry,%Water,

gFat,gLean

dry, g63.8

±1.613.0±0.923.2±0.9128.6

±4.026.1±1.746.7±1.663.9

±1.010.5±0.525.6±0.5137.2

±3.622.6±0.854.9±1.1e63.610.725.7139.523.41.21.30.1e3.03.155.80.6e63.910.026.1129.120.11.30.7e0.83.01.4e52.61.6e-8.1-2.5-2.3

1n = 4, all groups; results expressed as means ±SEM. a Significantly different from day 17 value(P < 0.05). " Significantly different from corresponding nonpregnant group value (P < 0.05).c Significantly different from day 5 value (P < 0.05).

carcass fat was statistically significant. Inrestricted pregnant rats, fasting caused asignificant decrease in carcass water andfat but lean dry tissue was not significantly changed. Absolute changes incarcass components in the fasted animalsbetween day 17 and 19 derived from themean values for the carcass compositionin the group killed before fasting, on day17, and the group killed after fasting, onday 19, are shown in tables 3 and 4. Thevalues indicate that well-fed pregnant ratslost more body fat when fasted thannonpregnant rats did (table 3).

In previously food-restricted rats (table4), what appeared to be a slightly greaterweight loss during fasting in pregnant ratscompared to nonpregnant rats was due toa greater loss of carcass water in the pregnant rats. Previously restricted pregnantrats lost 10.5 g carcass water during fasting whereas nonpregnant rats lost only 4g. Pregnant and nonpregnant rats lostsimilar amounts of fat and lean dry tissuestores, however (table 4).

During fasting, total body water wasreduced in both of the pregnant groups

but in the restricted pregnant rats, totalbody water fell below that of the ad libi-tum-fed nonpregnant fasted groups andwas not significantly different from restricted, fasted nonpregnant rats.

Liver weight. Liver weight decreasedin all fasted groups as shown in table 5.The liver weight of both pregnant groupsremained above that of the corresponding nonpregnant group during fasting.Well-fed pregnant and nonpregnant ratshad a comparable loss of liver weight during fasting, 3.8 and 3.2 g respectively.

In previously restricted rats, pregnantrats lost 1.4 g of liver weight during fasting and nonpregnant rats lost 2.2 g(table 5).

Fetal and placental weight. Table 6shows the fetal and placental weights ofpreviously ad libitum-fed or food-restricted fasted and not fasted rats.

On day 19, fasted rats previously fed adlibitum had fetuses weighing 92% andplacentas weighing 86% of the values fornot fasted rats. The differences were notsignificant by the two-tailed Student's t-test. In previously well-fed rats, placental

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TABLE 4

Carcass composition changes during fasting in groups previously food restricted1

Day 19

Day 17 Not fasted Fasted

Changeduringfasting

Pregnant restrictedWater, %Fat, %Lean dry, %

Water, gFat, gLean dry, g

67.2 ±1.1M7.1 ±1.3d

25.7 ±0.4d

134.2 ±2.4M14.2 ±2.6d51.3 ±0.2"

67.6 ±0.6"7.1 ±1.1"

25.3 ±0.5"

133.9 ±2.0M14.0 ±2.2"50.2 ±1.2

69.6 ±0.8cd2.4 ±0.8aed

28.0 ±0.4acd

123.7 ±2.0a«14.4 ±1.6acd

49.8 ±1.5"

K

-10.5-9.8-1.5

NonpregnantrestrictecWater,%Fat,%Lean

dry,%Water,

gFat,gLean

dry, g163.3

±1.010.4±1.226.3±0.8e122.6

±4.0"20.2±2.451.2±1.165.1

±1.09.0±1.125.9±0.8e125.9

±1.9"17.4±2.2C50.2±2.566.65.328.1118.69.550.11.11.1"«0.4°2.0"20acd1.1-4.0-10.7-1.1

1n = 4, all groups; results expressed as means ±SEM. a Significantly different from day 17 value(P < 0.05). b Significantly different from corresponding nonpregnant group value (P < 0.05). c Significantly different from day 5 value (P < 0.05). d Significantly different from corresponding adlibitum group (P < 0.05).

weight increased significantly during thefasting period and was not significantlylower than in not fasted rats.

Food restriction to day 19 reduced fetaland placental weight to 88 and 78% of control, respectively, but the decrease in fetalweight was not statistically significant.Fetal weight has been shown to be reduced significantly by food restrictioncontinued to day 21 (1). To determine if

the slowed rate of fetal growth establishedduring food restriction could be maintained during a fast, the fetal weights onday 19 of previously food-restricted fastedand not fasted rats were compared. Foodrestricted fasted rats had fetuses only 74%of controls, significantly lighter than thefetuses of the not fasted restricted rats.

Restricted rats also had significantlysmaller placentas than ad libitum-fed

TABLE 5

Liver weight in ad libitum-fed and food-restricted pregnant and nonpregnant rats'

Day19Pregnant

ad libNonpregnant ad libPregnant restrictedNonpregnant restrictedDay

511.8

±0.412.7 ±0.6Day

1716.2

±0.6""11.9 ±0.411.0 ±0.4e10.0 ±0.2aeNot

fastedg16.9

±0.2ab13.0 ±0.211.2 ±0.2^9.3 ±0.2aeFasted12.4

±0.2"^8.7 ±0.1e"9.6 ±O.!"0"67.7 ±O.lcdeLiver

wt changeduringfasting-3.8

-3.2-1.4-2.2

1Results expressed as means ±SEM. " Significantly different from corresponding day 5 value(P < 0.05). b Significantly different from corresponding nonpregnant group value (P < 0.05). c Significantly different from not fasted value (P < 0.05). d Significantly different from day 17 value(P < 0.05). e Significantly different from corresponding ad libitum group value (P < 0.05).

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TABLE 6

Fetal and placental weight and fetal composition in ad libitum-fed and food-restricted rats1

Day 19

Day 17 Not fasted Fasted

Fetal wt, gAd libitum fedFoodrestrictedPlacental

wt, gAd libitum fedFoodrestrictedFetal

% WaterAd libitum fedFood restricted0.81

±0.040.78 ±0.080.56

±0.020.45 ±0.03"90.5

±0.290.3 ±0.42.57

±0.15"2.25 ±0.07»0.77

±0.04a0.60 ±0.02ab89.0

±0.2«88.6 ±0.6a2.36

±0.12»1.91 ±0.05ab0.66

±0.03a0.55 ±0.02""89.1

±0.1"88.8 ±0.2"

1Results expressed as means ±SEM. a Significantly different from day 17 value (P < 0.05). b Significantly different from corresponding ad libitum group value (P < 0.05).

rats both at day 17 and day 19. Similarly,the placentas of fasted restricted rats weresignificantly smaller than those of fasted,previously well-fed rats.

Placental weight at day 19 was lower inanimals restricted from day 5 of gestationthan it was in animals fasted from day 17to 19. Although 2-day fasted rats hadsomewhat smaller placentas at day 19than did unfasted rats, the differenceswere not significant in either the previously well-fed or food-restricted groups.

Fetal body composition. The effect offasting on fetal body water is shown inTable 6. Fetal percent body water declined between days 17 and 19 in fastedand not fasted rats whether previouslywell fed or food restricted. In spite of thelarge effect on fetal weight, restriction followed by fasting did not significantly alterfetal percent body water at day 19.

DISCUSSION

This study confirms previous observations that in well-fed rats a normal rate offetal growth can be maintained during a2-day fast. During this fast pregnant animals lose more weight (conceptus subtracted) than similarly fed nonpregnantanimals. Carcass constituent losses areslightly higher in pregnant than in non-pregnant previously well-fed fasted ratsand include greater fat and water losseswith less lean tissue loss.

This finding is consistent with the well-established observation that fasted pregnant rats (4) and humans (5, 6) mobilizefat more readily than when not pregnant.It is believed that this more rapid response to starvation is designed to enable fetal use of glucose. Well-fed pregnant rats lost less lean dry tissue duringfasting than did nonpregnant rats, suggesting that total glucose utilization mayhave been less in the pregnant animals.The larger amount of food in the alimentary tract of pregnant rats or their liver gly-cogen stores may also have supplied theglucose needed by the conceptus duringthe fast. However, liver weight decreasedsimilarly during fasting in pregnant andnonpregnant rats.

Although previously well-fed pregnantrats lost more total weight (conceptus subtracted) than nonpregnant rats during fasting, changes in carcass composition andcarcass weights were not markedly different. These findings indicate that bodycomponents not included in the carcass,i.e., the liver and intestines, were responsible for the greater weight loss inthe pregnant group. The liver data showthat there was no large difference in liverweight losses in the two ad libitum-fedgroups when fasted. Therefore, thegreater net weight loss of the pregnantgroup was due to a larger loss in intestinalweight, probably due to the fact thatpregnant rats had more intestinal contents

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1830 LEDERMAN AND ROSSO

at the beginning of the fasting period andtherefore would defecate a larger amount.The different alimentary losses make itappear that pregnant rats lose more tissueweight than nonpregnant rats duringfasting, but they do not. Clearly, cautionmust be used to interpret weight changeswhen net weight without intestinal contents is not determined.

Since ad libitum-fed pregnant ratsgained more weight than nonpregnantrats prior to the fast, they ended the fastwith a higher carcass weight than non-pregnant fasted rats in spite of theirgreater weight loss during fasting.

In previously food-restricted rats, thereis a greater weight loss during fasting inpregnant rats than in nonpregnant ratsbut carcass analysis shows that the difference is due to greater decreases inbody water in the pregnant rats. Compared to nonpregnant rats, no additionalfat or lean dry tissue is lost during fasting in previously food restricted pregnant rats.

The decrease in body water in thefasted restricted pregnant group mayhave significance for fetal growth. It hasbeen shown that either food restriction ora low protein diet reduces the blood volume increase that normally occurs inpregnancy (7). Uterine blood flow is alsoreduced (8). Our total body water measures at day 17 (table 3) indicate that adlibitum-fed pregnant rats had higher bodywater content than ad libitum-fed non-pregnant rats. On day 17, restricted pregnant rats (table 4) did not have a higherbody water than well-fed nonpregnantrats (table 3).

If blood volume follows total bodywater, placental perfusion and fetalgrowth could be severely compromisedin the fasted restricted pregnant ratswhere total body water was markedly reduced. For example, in humans it hasbeen found that mothers of small babieshave a smaller plasma volume and totalbody water in late pregnancy thanmothers of large babies (9).

The reduction in total body waterwhich occurred during fasting in bothpregnant groups may be mediated byglucagon secretion. Glucagon has been

shown to induce natriuresis and waterloss during fasting in humans (10). Pregnant rats experience a much greaterfall in blood glucose during fasting thando nonpregnant rats (11) and they wouldbe expected to have a more marked glucagon response.

It is especially noteworthy that the lossof carcass fat in previously restricted pregnant and nonpregnant rats during fastingwas more than twice the amount lost bythe previously well-fed fasted animals.This surprising finding requires explanation.

Restricted rats began fasting with theiradaptive mechanisms already taxed. During fasting, they were exposed to a life-threatening stress and biological responses were probably pushed to theirlimits. After 3 days of fasting, pregnantrats have higher urinary epinephrineand norepinephrine excretion than non-pregnant rats (12). On the other hand,blood glucose is much lower during fasting in rats that are pregnant (2). Stress-stimulated lipolytic hormone release(cortisol, placental lactogen, growth hormone, glucagon) is probably also enhanced when food restriction precedesfasting (13-16). Strangely, although morefat was mobilized, it did not substitutefor other energy sources because totalcarcass nutrient losses were greater inboth groups of restricted fasted rats compared to ad libitum-fed rats when fasted.This result may also bea consequence ofheightened glucagon secretion since exogenous glucagon has been shown to increase protein catabolism in fasted rats(14). It is also known that energy expending activity is increased in food restrictedrats during a fast (17). In addition, absorption of nutrients from the intestines wouldhave ceased earlier in fasting in previously food-restricted rats, necessitatinggreater use of body stores.

Although fetal weight in fasted restricted rats was reduced significantly toonly 85% of the not fasted food restrictedvalue, placental weight was not significantly reduced by fasting. Fasted restricted rats had placentas 91.6% of theweight of the placentas of unfasted restricted rats. On the other hand, in not

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fasted groups placental weight at day 17and day 19 was significantly lower in restricted rats than in ad libitum-fed rats,but fetal weight was not. These resultsshow that fetal and placental growth although related, are not totally interdependent. As other workers have demonstrated, the tissue growing most rapidly ismost affected by a period of undernutri-tion (18). During the period when fastingwas imposed in the present study, fetalgrowth was much more rapid than placental growth and therefore it was moreaffected by the fast.

This study demonstrates that fastinglike food restriction significantly reducesfetal growth in undernourished rats. Theaccelerated metabolic adaptations tostarvation which characterize pregnancydo not protect the fetuses of undernourished mothers. It is likely that these adaptations are effective in previously well-fed animals because maternal stores ofglucogenic materials are sufficient to provide for fetal needs temporarily if themother can metabolize fat. These adaptations do not always protect the fetus.Fasting reduces fetal growth in food-restricted animals, in rats fasted more than2 days (19, 20), or in rats fasted so early inpregnancy that maternal metabolism hasnot yet made the adaptations typical oflate pregnancy, and maternal protein, fatand glycogen stores have not yet increased. In each of these cases the lack ofappropriate maternal substrates, particularly fat and carbohydrate, may renderuseless the maternal adaptive processeswhich would otherwise protect the fetusfrom periods of short-term maternal fasts.These considerations are of major significance for human pregnancy, where thebelief that "accelerated starvation" (21)

may prevent fetal growth retardation iseasily misapplied. Nevertheless, due tothe biological differences between rat andhuman pregnancy, the implications of thefindings for human gestation cannot bestated with certainty.

In a broader context these results infasted rats show that prior nutritionalstatus may alter the effect of a specific nutritional treatment on the mother or on thefetus. Thus, although fasting during preg

nancy might be always ill-advised, itwould be particularly undesirable inmothers previously not well nourished.

LITERATURE CITED

1. Lederman, S.A. & Rosso, P. (1980) Effects offood restriction on maternal weight and bodycomposition in pregnant and non-pregnant rats.Growth 44, 77-88.

2. Herrera, E., Knopp, R. H. & Freinkel, N.(1969) Carbohydrate metabolism in pregnancy. VI. Plasma fuels, insulin, liver composition, gluconeogenesis and nitrogen metabolismduring late gestation in the fed and fasted rat.J. Clin. Invest. 48, 2260-2270.

3. Steel, R. G. D. & Torrie, J. H. (1960) Principles and Procedures of Statistics, McGraw-Hill, New York.

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