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378 spa Abstracts 368 HYPOTHALAMIC·PITUITARY ·ADRENAL AXIS FUNCTION IN THE HUMAN FETUS: CJ Lockwood, N Mt Sinai School of Med., New York, NY. In hwnan pregnancy the relationship between the fetal and maternal hypothalamic-pituitary-adrenal (HPA) axes has yet to be established. Therefore, we measured corticotropin·releasing factor (CRF), cortico- tropin (ACfH) and cortisol (Cs) levels in 104 paired fetal and maternal serwn samples obtained at the time of cordocentesis between 18 and 39 weeks gestation. RESULTS CRF: Maternal CRF levels [1.54 ng/ml <±1.5)] were significantly higher than levels in either 26 nonpregnant controls [0.17 ng/ml <±G.07); p=0.001] or fetuses [0.34 ng/ml (±0.16] p=O.ool]. Maternal but not fetal CRF levels correlated strongly with gestational age (GA) (r=O.73; p=0.001 vs. r=O.OO4; p=O.9). ACTH: Fetal ACTH increased (r=0.355; p=0.001) while maternal ACTH decreased with GA (r=-0.21; p=0.037). ld: Both fetal and maternal Cs correlated with GA (r=0.569; p--o.ool and r=O.39; p=0.001). Significant Spearman Rank Correlations between HPA axes hormones in both fetal (F) and maternal (M) serwn are presented below (p<0.05): CRF-M Acrn-M Cs-M CRF-F Acrn-F Cs-F ACTH-M NS - 0.27 0.3 0.26 - 0.24 Cs-M 0.26 - 0.27 - 0.28 NS 0.53 CRF-F NS 0.30 - 0.28 NS NS ACTH-F NS 0.26 NS NS - 0.44 Cs-F 0.37 - 0.24 0.53 NS - 0.44 CONCLUSION: Maternal CRF increased dramatically across gestation. only weakly correlated with maternal and fetal CS and did not correlate with maternal ACTH. Although hormone bioactivity was not measured, these rmdings are consistent with a placental-derived CRF secretion. independent of feedback inhibition, which "inappropriately" drives maternal ACTH and Cs synthesis. Further- more a substantial contribution by CRF-stirnulated maternal Cs to the circulating fetal Cs pool may be responsible for the strong correlation between fetal and maternal Cs, their correlation with GA and their inverse correlation with declining maternal ACTH levels. 369 6·ENDORPHIN CONCENTRATIONS IN FETAL BLOOD DURING THE SECOND HALF OF PREGNANCY, CJ Lockwood, N Radunovic\ M Alvarez, RL Berkowitz. Mt Sinai School of Medicine, New York, NY. To evaluate changes in circulating B-endorphin (BEP) concentrations during fetal adaptation to possible intrauterine stress we measured BEP values in paired fetal and maternal blood samples obtained during 81 "uncomplicated" and 18 "complicated" (multiple cord punctures) cordocentesis between 18 and 39 weeks of gestation as well as in 24 term neonatal samples. RESULTS; The mean fetal BEP value from the uncomplicated procedure group [90.5 pg/ml (±59.4)] was significantly lower than BEP levels from neonates [228.4 pg/ml (±166.2); p <0.001], and from the complicated procedure group [771.2 pg/ml (±335.9); p< 0.001] but significantly higher than mean maternal values [70.5 pg/ml (±48.8); p< 0.02]. Fetal BEP levels from the uncomplicated but not from the complicated group significantly correlated with maternal values (Spearman rank r=O.47; p< 0.001 vs. r= ·0.08; p> 0.5). Fetal BEP levels did not correlate with gestational age. SUMMARY; These fmdings suggest that delivery and fetal adaptation to possible intrauterine stress are associated with significant increases in BEP levels. While a maternal and/or placental contribution to steady state circulating fetal BEP levels can not be excluded, it appears that the fetal pituitary is the primary source of circulating fetal BEP during possible intrauterine stress. January 1992 Am.J Obstet Gynecol 370 IfmlRL AN) FEW. ImUaS 10 AalIE II&1IXlm' mu:mIl. D. Ibit-elJn. Co 0IalIt", c. IIadt", B. F.isber, L CIadl", l'erimtal. BeseaIdl Jnst::i.tute, of Cirrirmti, Cirrimati, Olio IOJ£l AnaIda WS pn:xix:al a 2(XX)nl exchange transfusicn with plasJB/c:xystalloid in 11 pregpant ewes; 4 lDi=N:nt exchange traIlsfusicn with rJx>le blood. HalBtocri.t nrlrticn (fran 28±2.9 to 17±3.4%) resulted in d:crease5 in arterlal <XIlImt vs 9.8±2.1 ml/dl, amnic vs cmtIOl JJEm ± S.D.), uterire -34.8±5.2 vs -17.2±13.5%), rrean arterlal pressure -1l.3±5.2 vs uterire vasru1ar resistaoce -27.1±7.2 vs -10.1±18.2%), uterire vaws (3.6±0.7 vs 7.0±2.3 ml/dl), fetal -11.5±14.5 vs 6.1±10.6X) am fetal -23.0±14.6 vs 1.9±21.2".'). Katemal. iEart rate 15.6±18.8 vs -7.5±12.3l:pn), fetal Ill. 12.4±14.6 vs -10. 5±14. 7l:pn) am uterire extracticn ( 43.1±7 •5 vs 29.1±9. 2%) iocreased. By tre day, HAP, UVR am FllR retlJImi to cmtIOl l.e<iels am card:iac rutp.tt (C 0) had iocreased 15.3±15.7 vs -8.8!8.1%). raJBinerl cEcreasai -33.7±1l.1 vs -8.4±10.1%). Fetal PI, ktate am IBIBtocrlt, natemal. PI, ktate, am uterire blood flow (UBF) \e:'e Acute amnia proOObly results in uterire vasocaJStri.cti as lJBF did oot :iocJ:ease despite iocreased C ° am cEcreasai viscosit;y of .nmi.c blood. is limited cEcreasai 02C am lack of :iocJ:ease in lJBF. iocreased uterire 02 extracticn, tre fetus becares mildly hypoxani.c. 371 EFFECT OF SOUND STIMULATION ON FETAL CEREBRAL METABOLISM AND FETAL OXYGENATION, C. R. Chao", G P. GuyX, K. E. Jack" S. S. Daniel", R. I. Stark X , Dept. of Ob/Gyn, Columbia New York, NY Previous studies have demonstrated that sound stimulation in- creases glucose metabolism in many regions of the fetal brain. However, the metabolic fate of that glucose has not previously been determined. Methods: Near-term fetal sheep were chroni- cally catheterized in brachial arteries and the superior sagittal si- nus. Sound stimulation was provided by 1) miniature waterproofed earphones attached to the fetus and 2) an electrolarynx applied to the maternal abdomen. Arterial and venous (sagittal sinus) sam- ples were taken for glucose, oxygen, and lactate concentrations and blood gases prior to and during sound stimulation. All studies took place in the high state. Results: Arterial and venous oxygen content and p02 were signijicantly decreased by 6-7% during sound stimulation. The arteriovenous difference for oxygen was unaffected by sound stimulation, whereas that for glucose in- creased signijicantly. The glucose:oxygen quotient, an index of the adequacy of oxygen uptake for glucose uptake, increased from 0.88 ± 0.08 to 1.13 ± 0.12 (p<O.Ol). These findings are consistent stimulated or aerobic glycolysis which has been shown to in- crease brain lactate concentration in other models. No change in lactate arteriovenous difference could be detected, but this may be due to the relative of the ovine fetal blood-brain barrier to lactate. The metabolic changes were similar during both types of stimuli, but the electrolarynx group alone a tran- sient increase in arterial blood pressure. Because sound stimula- tion may adversely affect fetal oxygenation and cerebral metabolism, caution should be exercised in the fetal diagnostic use of sound stimuli. (HD 26600)

371 Effect of Sound Stimulation on Fetal Cerebral Metabolism and Fetal Oxygenation

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378 spa Abstracts

368 HYPOTHALAMIC·PITUITARY ·ADRENAL AXIS FUNCTION IN THE HUMAN FETUS: CJ Lockwood, ~, N Radunovi~ Mt Sinai School of Med., New York, NY.

In hwnan pregnancy the relationship between the fetal and maternal hypothalamic-pituitary-adrenal (HPA) axes has yet to be established. Therefore, we measured corticotropin·releasing factor (CRF), cortico­tropin (ACfH) and cortisol (Cs) levels in 104 paired fetal and maternal serwn samples obtained at the time of cordocentesis between 18 and 39 weeks gestation. RESULTS CRF: Maternal CRF levels [1.54 ng/ml <±1.5)] were significantly higher than levels in either 26 nonpregnant controls [0.17 ng/ml <±G.07); p=0.001] or fetuses [0.34 ng/ml (±0.16] p=O.ool]. Maternal but not fetal CRF levels correlated strongly with gestational age (GA) (r=O.73; p=0.001 vs. r=O.OO4; p=O.9). ACTH: Fetal ACTH increased (r=0.355; p=0.001) while maternal ACTH decreased with GA (r=-0.21; p=0.037). ld: Both fetal and maternal Cs correlated with GA (r=0.569; p--o.ool and r=O.39; p=0.001). Significant Spearman Rank Correlations between HPA axes hormones in both fetal (F) and maternal (M) serwn are presented below (p<0.05):

CRF-M Acrn-M Cs-M CRF-F Acrn-F Cs-F ACTH-M NS - 0.27 0.3 0.26 - 0.24 Cs-M 0.26 - 0.27 - 0.28 NS 0.53 CRF-F NS 0.30 - 0.28 NS NS ACTH-F NS 0.26 NS NS - 0.44 Cs-F 0.37 - 0.24 0.53 NS - 0.44 CONCLUSION: Maternal CRF increased dramatically across gestation. only weakly correlated with maternal and fetal CS and did not correlate with maternal ACTH. Although hormone bioactivity was not measured, these rmdings are consistent with a placental-derived CRF secretion. independent of feedback inhibition, which "inappropriately" drives maternal ACTH and Cs synthesis. Further­more a substantial contribution by CRF-stirnulated maternal Cs to the circulating fetal Cs pool may be responsible for the strong correlation between fetal and maternal Cs, their correlation with GA and their inverse correlation with declining maternal ACTH levels.

369 6·ENDORPHIN CONCENTRATIONS IN FETAL BLOOD DURING THE SECOND HALF OF PREGNANCY, CJ Lockwood, N Radunovic\ M Alvarez, RL Berkowitz. Mt Sinai School of Medicine, New York, NY.

To evaluate changes in circulating B-endorphin (BEP) concentrations during fetal adaptation to possible intrauterine stress we measured BEP values in paired fetal and maternal blood samples obtained during 81 "uncomplicated" and 18 "complicated" (multiple cord punctures) cordocentesis between 18 and 39 weeks of gestation as well as in 24 term neonatal samples. RESULTS; The mean fetal BEP value from the uncomplicated procedure group [90.5 pg/ml (±59.4)] was significantly lower than BEP levels from neonates [228.4 pg/ml (±166.2); p <0.001], and from the complicated procedure group [771.2 pg/ml (±335.9); p< 0.001] but significantly higher than mean maternal values [70.5 pg/ml (±48.8); p< 0.02]. Fetal BEP levels from the uncomplicated but not from the complicated group significantly correlated with maternal values (Spearman rank r=O.47; p< 0.001 vs. r= ·0.08; p> 0.5). Fetal BEP levels did not correlate with gestational age. SUMMARY; These fmdings suggest that delivery and fetal adaptation to possible intrauterine stress are associated with significant increases in BEP levels. While a maternal and/or placental contribution to steady state circulating fetal BEP levels can not be excluded, it appears that the fetal pituitary is the primary source of circulating fetal BEP during possible intrauterine stress.

January 1992 Am.J Obstet Gynecol

370 IfmlRL AN) FEW. ImUaS 10 AalIE II&1IXlm' mu:mIl. D. Ibit-elJn. Co 0IalIt" , c. IIadt" , B. F.isber , L CIadl" , l'erimtal. BeseaIdl Jnst::i.tute, lbi.~t;y of Cirrirmti, Cirrimati, Olio IOJ£l

AnaIda WS pn:xix:al ~ a 2(XX)nl exchange transfusicn with plasJB/c:xystalloid in 11 pregpant ewes; 4 lDi=N:nt exchange traIlsfusicn with rJx>le blood. HalBtocri.t nrlrticn (fran 28±2.9 to 17±3.4%) resulted in d:crease5 in arterlal ~ <XIlImt (~C.)(6.4±O.6 vs 9.8±2.1 ml/dl, amnic vs cmtIOl JJEm ± S.D.), uterire ~ cElivery(~t) (~ -34.8±5.2 vs -17.2±13.5%), rrean arterlal pressure (HAP)(~ -1l.3±5.2 vs -2.0±4.~), uterire vasru1ar resistaoce (UVR)(~ -27.1±7.2 vs -10.1±18.2%), uterire vaws ~C (3.6±0.7 vs 7.0±2.3 ml/dl), fetal P.02(~ -11.5±14.5 vs 6.1±10.6X) am fetal ~C. (~ -23.0±14.6 vs 1.9±21.2".'). Katemal. iEart rate QIIR)(~ 15.6±18.8 vs -7.5±12.3l:pn), fetal Ill. (~ 12.4±14.6 vs -10. 5±14. 7l:pn) am uterire ~ extracticn ( 43.1±7 • 5 vs 29.1±9. 2%) iocreased. By tre f~ day, HAP, UVR am FllR retlJImi to cmtIOl l.e<iels am card:iac rutp.tt (C 0) had iocreased (~ 15.3±15.7 vs -8.8!8.1%). ~t raJBinerl cEcreasai (~ -33.7±1l.1 vs -8.4±10.1%). Fetal PI, ~, ktate am IBIBtocrlt, natemal. PI, ~, ~, ktate, am uterire blood flow (UBF) \e:'e ~. Acute amnia proOObly results in uterire vasocaJStri.cti as lJBF did oot :iocJ:ease despite iocreased C ° am cEcreasai viscosit;y of .nmi.c blood. ~t is limited ~ cEcreasai 02C am lack of :iocJ:ease in lJBF. ~ite iocreased uterire 02 extracticn, tre fetus becares mildly hypoxani.c.

371 EFFECT OF SOUND STIMULATION ON FETAL CEREBRAL METABOLISM AND FETAL OXYGENATION, C. R. Chao", G P. GuyX, K. E. Jack" S. S. Daniel", R. I. StarkX, Dept. of Ob/Gyn, Columbia Univers~y, New York, NY

Previous studies have demonstrated that sound stimulation in­creases glucose metabolism in many regions of the fetal brain. However, the metabolic fate of that glucose has not previously been determined. Methods: Near-term fetal sheep were chroni­cally catheterized in brachial arteries and the superior sagittal si­nus. Sound stimulation was provided by 1) miniature waterproofed earphones attached to the fetus and 2) an electrolarynx applied to the maternal abdomen. Arterial and venous (sagittal sinus) sam­ples were taken for glucose, oxygen, and lactate concentrations and blood gases prior to and during sound stimulation. All studies took place in the high vo~age state. Results: Arterial and venous oxygen content and p02 were signijicantly decreased by 6-7%

during sound stimulation. The arteriovenous difference for oxygen was unaffected by sound stimulation, whereas that for glucose in­creased signijicantly. The glucose:oxygen quotient, an index of the adequacy of oxygen uptake for glucose uptake, increased from 0.88 ± 0.08 to 1.13 ± 0.12 (p<O.Ol). These findings are consistent w~h stimulated or aerobic glycolysis which has been shown to in­crease brain lactate concentration in other models. No change in lactate arteriovenous difference could be detected, but this may be due to the relative impermeabil~y of the ovine fetal blood-brain barrier to lactate. The metabolic changes were similar during both types of stimuli, but the electrolarynx group alone exhib~ed a tran­sient increase in arterial blood pressure. Because sound stimula­tion may adversely affect fetal oxygenation and cerebral metabolism, caution should be exercised in the fetal diagnostic use of sound stimuli. (HD 26600)