Feeding frequency during pregnancy phase shifts the temperature rhythm and synchronizes the cortisol...

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Volume 176, Number l, Part 2 ~PO Abstracts $168 Am J Obstet Gynecol 564 PROTEIN-CALORIC RESTRICTION DURING PREGNANCY AFFECTS THE ADRENAL-PLACENTAL AXIS AND DECREASES NEWBORN WEIGHT IN A PRIMATE, THE CEBUS APELLA. MP RacabmTen ~,* GJ Valenzuela, M. SeronFerrerL Facultad Cs. Biologicas, P Univ. Catolica de Chile y *Dept. Ob/Gyn, San Bernardino Med Center and Western Univ Health Sci., San Bernardino, California. OBJECTIVES. The objective was to asses the effect of maternal under nutrition upon the maternal adrenal-placental axis STUDY DESIGN. We subjected 6 females Cebus apella to a restricted diet (12% protein-730 cal/day) during pregnancy. Fifteen females fed standard diet (19% protein-912 cal/day) were used as controls. Between 125 and 145 days of gestation (GA), we measured (RIA) maternal plasma E2 as an indirect indicator of FA function and F as an iudicator of maternal adrenal function. We determined newborn weight (NW) and GA at birth. Results: X + SEM NW (g) GA (days) E2 (ng/ml) F (ug/ml) Control 197 + 5.2 154.2 + 1 57.1 + 4 2.35 + 0.2 (n = 15) (7) Restricted 177.5 + 6.5 156.2 + 2.2 27.2 + 4.6* 3.4 + 0.3 (6)* (5)* *p < 0.05 Vs controls, Mann-Whitney test. ( ) = nmnber of animals. CONCLUSIONS: Under nutrition 1) decreased newborn weight 2) increased maternal cortisol and decreased maternal E2. This last finding suggest suppressiou of tire FA by feedback of the excess of maternal cortisol upon the fetal hypotbalamus or pituitmy. Financed by CHI/LID/2, SB- CMC, Fondecyt 1951.038. 566 THE EFFECTS OF PHYSIOLOGIC ELEVATIONS OF INSULIN ON HEPATIC AND PERIPHERAL INSULIN RESISTANCE IN THE PREG- NANT DOG. T. Papa, 34. Smith*, D. Lacy*, M. Monohan*, C. Connolly.* Dept. of Ob/Gyn, Vanderbilt University, Nashville, TN. OBJECTIVE: To evaluate the effects of physiologic increases in insulin on hepatic and peripheral glucose metabolism during late pregnancy in the dog. STUDY DESIGN: Studies were performed on 4 pregnant (P) and 5 nonpregnant (NP) 18hr fasted conscious dogs in which sampling cadmters were surgically implanted two weeks earlier in the portal and left common hepatic veins and the femoral artery. Somatostatin was infused to inhibit endogenous release of insulin and glucagon during 3 120 minute periods. In period 1, iusulin and glucagon were replaced intraportally at basal rates to assess basal metabolism; in period 2, the insulin infusion was increased to raise insulin levels by 2 p~U/ml, which decreases net hepatic glucose output (NHGO) by ~ 70% in tim NP state; in period 3, the insulin infusion was increased to elevate insulin levels to 5 times the basal level, which com- pletely suppresses NHGO and increases glucose utilization threefold in the NP state. Glucose was infused in periods 2 and 3 to maintain euglyeemia, with the rate of glucose infusion used as an index of peripheral glucose utilization. RESULTS: In both P and NP dogs, both of the increases in insulin resulted in similar suppression of NHGO. P dogs required significantly less exogenous glucose to maintain euglycemia during period 3 than NP dogs. NHGO P 2.0 + 0.5 0.8 + 0.2 0.1 • 0.3 (mg/kg/min) NP 1.5 -+ 0.2 0.7 +- 0.1 0.3 _+ 0.2 Exogenous glucose P -- 2.2 + 0.4 5.7 _+ 0.5 (mg/kg/min) NP -- 1.8 -+ 0.4 10.6 + 1.8 CONCLUSIONS: Late pregnancy does not appear to be associated with hepatic insulin resistance in the dog. However, significant peripheral resistance to insulin action is confirmed. 565 FEEDING FREQUENCY DURING PREGNANCY PHASE SHIFTS THE TEMPERATURE RHYTHM AND SYNCHRONIZES THE CORTISOL RHYTHM IN Cebus apella NEWBORNS. Rajas, t~., M Ve~gara x, GJ Valenzu- ela, P Recabarren ~, M Ser6n-FerrgL P U Cat61ica y *San Bernardino Medl Ctr, and Western Univ., San Bernardino, California. OBJECTIVE. Our aims are to study whether temperature and cortisol circadian rhythms are present in newborns of another primate species, the Cebus apella, in whether these rhythms may be entrained by environmental signals experienced during gestation. DESIGN STUDY. A group (n - 10) were fed 4 times a day while the second group (n ~ 6) were fed twice. Amount and cmnposition of the diet was the same for the two groups. Females were weighed at weekly intel-Jals to follow up pregnancies. Gestational length and newborn weight at birth were recorded. At 4 d, newborns were separated from their mother. Blood samples were taken at 2-3 h lot 24 or 48-h, and rectal temperature at one or two h. Cortisol was measured by RIA. The presence of 24-h rhythms in individuals and in the nman data was analyzed by cosinor. A result was considered significant when p < 0.05. RESULTS: The treatment had no effect on gestational length or infant weight. 24-h rhythms of temperature and cortisol were present in newborns of both feeding regimes at 4 days of age. However, in newborns whose mothers were fed 4 times/day during pregnancy, the tenrperature rhythms were synchronized between newborns while the cortisol rhythms were not. In contrast, the temperature and cortisol rhythms were synchronized in newborns of mothers fed 2 times/day. In addition, the acrophases of the rectal temperature rbythm were shifted in newborns of mothers fed 2 tinms a day" (1580 vs 0295 h in the 4 feedings a day group). CONCLUSIONS: 1) Cebus apella newborns present temperature and cortisol rhythms at 4 d of age. 2) Feeding frequency during pregnancy is a zeitgeber tbr the temperature rhythm determining a phase shift of the temperature rhythnL 3) Feeding frequency provides a zeitgeber for the newborn cortisol rhythm. Supported by Fondecyt 1951-038, SBMC Founda- tion and CHI/LID/2 567 PERSISTENT FETAL GROWTH RETARDATION IN AN OVINE MODEL OF PLACENTAL INSUFFICIENCY. H. Galan #x, M. Hussey #, M Chung@~A. # . ,~ # Barbera-,.[ Hobbins , F. Battaglia , G. Meschia . Dept. Ob/Gyn , Biometrics@, and Ped*. Univ. Colo. Hlth. Sci. Ctr., Denver, CO." Ob/Gyn Clinic and ISBM San Paolo, Milan, ltaly. OBJECTIVE: Fetal growth retardation (FGR) in an ovine model has been previously described following exposure to environmental heat stress for 80 days beginning at 35 days' gestation. Our objective was to determine whether FGR could be reversed upon removal of the heat stress after 55 days of exposure. STUDY DESIGN: Beginning at 35 days' gestation (term = 147 days), 4 ewes were exposed to heat stress for 55 days (Heat 55) and then removed. Three control ewes were added to 37 previously studied normal ewes. Serial fetal biomeu-ic ultrasonographic measurements (biparietal diameter (BPD), abdominal circmnference (AC), femur length (FL) and tibia length (TL)) were obtained beginning at 50 days' gestation. Growth curves were calculated for each parameter and compared to 40 normal fetuses and 4 heat stressed fetuses exposed for 80 days (Heat 80). Regression lines, 95th percent confidence intervals and slopes were determined for each study group. RESULTS: Indices of somatic growth (AC, FL, TL) for the control group were significantly greater than either the Heat 55 or Heat 80 groups (p < 0.001). In each heat stressed group, a suggestion of asymmetric growth retardation was evident by a BPD/AC ratio which was significantly higher in both Heat 55 and Heat 80 fetuses compared to control fetuses (p < 0.001). The slopes for the AC, TL, and FL versus time became significantly different between the control and Heat 55 fetuses at 78, 80, and 102 days respectively. Heat 50 fetuses had significantly greater AC and FL when compared to Heat 80 fetuses. Although not significant due to an insufficient "n" in each group, all Heat 80 animals (avg = 1272 grn) were smaller than the Heat 55 animals (avg = 1870 gm). CONCLUSIONS: The growth pattern reflected by the fetal biomen 7 of the Heat 55 and Heat 80 fetuses is consistent with asymmen-ic growth retardation. The FGR pattern is not different between sheep that are heat-stressed for either 55 or 80 days. This suggests that the initial insult affecting fetal growth occurs early in gestation, and that the effect persists even upon removal of the heat stress. Given the larger head to body ratio between Heat 55 and 80 day fetuses, we speculate that with additional animals, significant ditfi~rences may be detected for birthweight between the groups.

Transcript of Feeding frequency during pregnancy phase shifts the temperature rhythm and synchronizes the cortisol...

Volume 176, Number l , Part 2 ~PO Abst rac ts $168 Am J Obstet Gynecol

564 PROTEIN-CALORIC RESTRICTION DURING PREGNANCY AFFECTS T H E ADRENAL-PLACENTAL AXIS AND DECREASES N E W B O R N WEIGHT IN A PRIMATE, T H E CEBUS APELLA. MP RacabmTen ~,* GJ Valenzuela, M. SeronFerrerL Facultad Cs. Biologicas, P Univ. Catolica de Chile y *Dept. Ob/Gyn, San Bernardino Med Center and Western Univ Health Sci., San Bernardino, California.

OBJECTIVES. The objective was to asses the effect of maternal under nutrition upon the maternal adrenal-placental axis

STUDY DESIGN. We subjected 6 females Cebus apella to a restricted diet (12% protein-730 cal/day) during pregnancy. Fifteen females fed standard diet (19% protein-912 cal/day) were used as controls. Between 125 and 145 days of gestation (GA), we measured (RIA) maternal plasma E2 as an indirect indicator of FA function and F as an iudicator of maternal adrenal function. We determined newborn weight (NW) and GA at birth. Results: X + SEM

NW (g) GA (days) E2 (ng/ml) F (ug/ml)

Control 197 + 5.2 154.2 + 1 57.1 + 4 2.35 + 0.2 (n = 15) (7)

Restricted 177.5 + 6.5 156.2 + 2.2 27.2 + 4.6* 3.4 + 0.3 (6)* (5)*

*p < 0.05 Vs controls, Mann-Whitney test. ( ) = nmnber of animals.

CONCLUSIONS: Under nutrition 1) decreased newborn weight 2) increased maternal cortisol and decreased maternal E2. This last finding suggest suppressiou of tire FA by feedback of the excess of maternal cortisol upon the fetal hypotbalamus or pituitmy. Financed by CHI/LID/2, SB- CMC, Fondecyt 1951.038.

566 T H E EFFECTS OF PHYSIOLOGIC ELEVATIONS OF INSULIN O N HEPATIC AND PERIPHERAL INSULIN RESISTANCE IN T H E PREG- N A N T DOG. T. Papa, 34. Smith*, D. Lacy*, M. Monohan*, C. Connolly.* Dept. of Ob/Gyn, Vanderbilt University, Nashville, TN.

OBJECTIVE: To evaluate the effects of physiologic increases in insulin on hepatic and peripheral glucose metabolism during late pregnancy in the dog.

STUDY DESIGN: Studies were performed on 4 pregnant (P) and 5 nonpregnant (NP) 18hr fasted conscious dogs in which sampling cadmters were surgically implanted two weeks earlier in the portal and left common hepatic veins and the femoral artery. Somatostatin was infused to inhibit endogenous release of insulin and glucagon during 3 120 minute periods. In period 1, iusulin and glucagon were replaced intraportally at basal rates to assess basal metabolism; in period 2, the insulin infusion was increased to raise insulin levels by 2 p~U/ml, which decreases net hepatic glucose output (NHGO) by ~ 70% in tim NP state; in period 3, the insulin infusion was increased to elevate insulin levels to 5 times the basal level, which com- pletely suppresses NHGO and increases glucose utilization threefold in the NP state. Glucose was infused in periods 2 and 3 to maintain euglyeemia, with the rate of glucose infusion used as an index of peripheral glucose utilization.

RESULTS: In both P and NP dogs, both of the increases in insulin resulted in similar suppression of NHGO. P dogs required significantly less exogenous glucose to maintain euglycemia during period 3 than NP dogs.

NHGO P 2.0 + 0.5 0.8 + 0.2 0.1 • 0.3 (mg/kg/min) NP 1.5 -+ 0.2 0.7 +- 0.1 0.3 _+ 0.2 Exogenous glucose P - - 2.2 + 0.4 5.7 _+ 0.5 (mg/kg/min) NP - - 1.8 -+ 0.4 10.6 + 1.8

CONCLUSIONS: Late pregnancy does not appear to be associated with hepatic insulin resistance in the dog. However, significant peripheral resistance to insulin action is confirmed.

565 FEEDING FREQUENCY D U R I N G PREGNANCY PHASE SHIFTS T H E TEMPERATURE R H Y T H M AND SYNCHRONIZES T H E CORTISOL RHYTHM IN Cebus apella NEWBORNS. Rajas, t~., M Ve~gara x, GJ Valenzu- ela, P Recabarren ~, M Ser6n-FerrgL P U Cat61ica y *San Bernardino Medl Ctr, and Western Univ., San Bernardino, California.

OBJECTIVE. Our aims are to study whether temperature and cortisol circadian rhythms are present in newborns of another primate species, the Cebus apella, in whether these rhythms may be entrained by environmental signals experienced during gestation.

DESIGN STUDY. A group (n - 10) were fed 4 times a day while the second group (n ~ 6) were fed twice. Amount and cmnposition of the diet was the same for the two groups. Females were weighed at weekly intel-Jals to follow up pregnancies. Gestational length and newborn weight at birth were recorded. At 4 d, newborns were separated from their mother. Blood samples were taken at 2-3 h lot 24 or 48-h, and rectal temperature at one or two h. Cortisol was measured by RIA. The presence of 24-h rhythms in individuals and in the nman data was analyzed by cosinor. A result was considered significant when p < 0.05.

RESULTS: The treatment had no effect on gestational length or infant weight. 24-h rhythms of temperature and cortisol were present in newborns of both feeding regimes at 4 days of age. However, in newborns whose mothers were fed 4 times/day during pregnancy, the tenrperature rhythms were synchronized between newborns while the cortisol rhythms were not. In contrast, the temperature and cortisol rhythms were synchronized in newborns of mothers fed 2 times/day. In addition, the acrophases of the rectal temperature rbythm were shifted in newborns of mothers fed 2 tinms a day" (1580 vs 0295 h in the 4 feedings a day group).

CONCLUSIONS: 1) Cebus apella newborns present temperature and cortisol rhythms at 4 d of age. 2) Feeding frequency during pregnancy is a zeitgeber tbr the temperature rhythm determining a phase shift of the temperature rhythnL 3) Feeding frequency provides a zeitgeber for the newborn cortisol rhythm. Supported by Fondecyt 1951-038, SBMC Founda- tion and CHI/LID/2

567 PERSISTENT FETAL GROWTH RETARDATION IN AN OVINE MODEL OF PLACENTAL INSUFFICIENCY. H. Galan #x, M. Hussey #, M Chung@ ~ A.

# . ,~ # Barbera-,.[ Hobbins , F. Battaglia , G. Meschia . Dept. Ob/Gyn , Biometrics@, and Ped*. Univ. Colo. Hlth. Sci. Ctr., Denver, CO." Ob/Gyn Clinic and ISBM San Paolo, Milan, ltaly.

OBJECTIVE: Fetal growth retardation (FGR) in an ovine model has been previously described following exposure to environmental heat stress for 80 days beginning at 35 days' gestation. Our objective was to determine whether FGR could be reversed upon removal of the heat stress after 55 days of exposure.

STUDY DESIGN: Beginning at 35 days' gestation (term = 147 days), 4 ewes were exposed to heat stress for 55 days (Heat 55) and then removed. Three control ewes were added to 37 previously studied normal ewes. Serial fetal biomeu-ic ultrasonographic measurements (biparietal diameter (BPD), abdominal circmnference (AC), femur length (FL) and tibia length (TL)) were obtained beginning at 50 days' gestation. Growth curves were calculated for each parameter and compared to 40 normal fetuses and 4 heat stressed fetuses exposed for 80 days (Heat 80). Regression lines, 95th percent confidence intervals and slopes were determined for each study group.

RESULTS: Indices of somatic growth (AC, FL, TL) for the control group were significantly greater than either the Heat 55 or Heat 80 groups (p < 0.001). In each heat stressed group, a suggestion of asymmetric growth retardation was evident by a BPD/AC ratio which was significantly higher in both Heat 55 and Heat 80 fetuses compared to control fetuses (p < 0.001). The slopes for the AC, TL, and FL versus time became significantly different between the control and Heat 55 fetuses at 78, 80, and 102 days respectively. Heat 50 fetuses had significantly greater AC and FL when compared to Heat 80 fetuses. Although not significant due to an insufficient "n" in each group, all Heat 80 animals (avg = 1272 grn) were smaller than the Heat 55 animals (avg = 1870 gm).

CONCLUSIONS: The growth pattern reflected by the fetal biomen 7 of the Heat 55 and Heat 80 fetuses is consistent with asymmen-ic growth retardation. The FGR pattern is not different between sheep that are heat-stressed for either 55 or 80 days. This suggests that the initial insult affecting fetal growth occurs early in gestation, and that the effect persists even upon removal of the heat stress. Given the larger head to body ratio between Heat 55 and 80 day fetuses, we speculate that with additional animals, significant ditfi~rences may be detected for birthweight between the groups.