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Fetal plasma erythropoietin concentration in severe growth retardation
Int J Gynecoi Obstet, 1993, 43: 91-100 International Federation of Gynecology and Obstetrics
91
Citations from the Literature
This is a selection of abstracts taken from the literature in the field of obstetrics and gynecology which the Journal’s Editors feel may be of interest to our readers*
DISEASES IN PREGNANCY PIateIet4tetiv8ting factor mmotedved~eprlplnndcs
-
acetylbydrolase
activity
in
Maki N.; Magness R.R.; Miyaura S.; Gant N.F.; Johnston J.M. USA AM J OBSTET GYNECOL 1993 168/l I (50-54) Objective: The purpose of our study was to evaluate the hypothesis that pregnancy is associated with decreased plateletactivating factor-acetylhydrolase activity in women with normote&on, but not in women with hypertension. Study design: We evaluated plasma platelet-activating factor-acetylhydrolase activity in normal nonpregnant women (n = lo), normal pregnant women (n = 24), pregnant women with pregnancyinduced hypertension-preeclampsia (n = 7), and a group of men with normotension (n = 10). Results: Platelet-activating factoracetylhydrolase activity was lower at 32 weeks of gestation during normal pregnancies compared with nonpregnant controls (P < 0.001); however, in women with pregnancy-induced hypertension-preeclampsia, platelet-activating factor-acetylhydrolase activity was not decreased. Platelet-activating factoracetylhydrolase activity in men was higher than in all women (P < 0.01). Conclusion: Pregnant women with normotension may be refractory to pressor agents such as angiotensin II in part because of the decrease in plasma platelet-activating factor-acetylhydrolase activity, which results in an increase in platelet-activating factor. In contrast, enxyme activity is not decreased in pregnant women with hypertension, who have increased sensitivity to various pressor agents. Lowdose aapirIa In preventIon and treatment of intr8tine growth retud8tion and pregmncy-indmced hypertedon
Paraxzini F.; Benedetto C.; Frusca T.; Gregorini G.; Bocciolone L.; Marozio L.; Romero M.; Danesino V.; De Gaetano G.; Gastaidi A.; Massobrio M.; Remuxxi G.; Tognoni G.; Guaschino S.; Bianchi C.; Valcamonico A.; Giambuxxi M.; Ammendola D.; Casucci F.; et al.
*Generated from the Excerpta Medica Database, EMBASE.
ITA LANCET 1993 34118842(396-400) Meta-analysis of data from several controlled trials has shown that lowdose aspirin reduces the risk of pregnancyinduced hypertension (PHI) and intrauterine growth retardation (IUGR) in women at high risk of these disorders. We have asses& the etlicacy of low-dose aspirin in women judged to be at moderate risk. Women were included on prophylactic criteria - age under 18 or over 40 years, mild or moderate chronic hypertension (diastolic pressure between 90 and 110 mm Hg), nephropathy with normal renal function and blood pressure, history of PIH or IUGR, and twin pregnancy - or therapeutic criteria - PIH or early signs of IUGR in current pregnancy. Eligible women were randomly assigned treatment with 50 mg aspirin daily until delivery (583) or no treatment (523); 18 and 46 women, respectively, were lost to follow-up. The groups were well matched for baseline characteristics. We found no differences between the no-treatment and aspirin groups in numbers of spontaneous (5 vs. 2) or therapeutic (1 vs. 2) abortions, stillbirths (14 vs. 13), perinatal mortality (35.7 vs. 28.6 per 1000 births), mean birthweight (2858 [SD 7291vs. 2874 17951g), proportion of infants with birthweights below the 10th centile (95 [18.3%] vs. 117 [19.0%]), or births before 37 weeks’ gestation (184 [35.6%] vs. 209 [33.9%]). Nor did the groups differ in the frequency of PIH with or without proteinuria (51 [15.2%] vs. 81 [19.3%]). There was no difference in mean birthweight between the treatment groups in separate analyses according to criteria for trial entry and week of gestation at randomization. Our study gives little support to the notion that low-dose aspirin is beneficial in women at moderate risk of PIH or IUGR. FetaI pIasma erytbopoietin
conceetration
in severe growth
refdathm
Snijders R.J.M.; Abbas A.; Melby 0.; Ireland R.M.; Nicolaides K.H. GBR AM J OBSTET GYNECOL 1993 168/2 (615-619) Objective: The aim of this study was to determine whether hypoxemia induces an increase in plasma erythropoietin concentration in human fetal life and, if so, whether this response stimulates fetal erythropoiesis. Study design: The plasma Int J Gynecol Obsret 43
92
Citations from the Literature
erythropoietin concentration in blood samples from 33 smallfor-gestational-age fetuses at 26 to 38 weeks’ gestation was measured. Measurements were compared with the reference range for gestation, and associations with Po2, pH, and erythroblast and erythrocyte counts were examined. Results: The mean plasma erythropoietin concentration in the smallfor-gestational-age fetuses was significantly increased, and the degree of increase was significantly associated both with fetal acidemia and, more strongly, with fetal erythroblastosis. Conclusion: Erythropoietin production in response to tissue hypoxia occurs from at least 26 weeks’ gestation with measurable physiologic effects on erythropoiesis. Furthermore, more accurate assessment of tissue oxygenation may be obtained by measuring the erythroblast count rather than the blood pH.
Lowdose aspirin in the prevention of preeclampsia and fetal growth retardation: Rationale, mechanisms, and clinical trials
Dekker G.A.; Sibai B.M. USA AM J OBSTET GYNECOL 1993 168/l 1(214-227) Preeclampsia is characterized by a functional imbalance between vascular prostacyclin and thromboxane A2 production. On the basis of the hypothesis that preeclampsia is at least partially caused by an increase in thromboxane AZ, some studies attempted to correct this pathologic condition by pharmacologic manipulation with low-dose aspirin. The current literature suggests that the use of low-dose aspirin during pregnancy is safe with regard to congenital anomalies and fetal, neonatal, and maternal cardiovascular physiologic state and hemostasis. Aspirin at least partially corrects the pathologic increase in angiotensin II sensitivity that precedes the clinical development of preeclampsia. In addition, some clinical trials have demonstrated that low-dose aspirin is effective in reducing the incidence of preeclampsia and/or fetal growth retardation in selected high-risk women. Currently, large clinical trials are in progress to evaluate the effectiveness and side effects of the use of low-dose aspirin in preventing preeclampsia and/or fetal growth retardation. Until these studies have been completed, it will remain unclear whether antiplatelet therapy, such as lowdose aspirin, should be adopted for the prevention of either preeclampsia or fetal growth retardation. Fetal plasma erythropoietin in pregnancies complicated by maternal diabetes mellitus
Salvesen D.R.; Brudenell J.M.; Snijders R.J.M.; Ireland R.M.; Nicolaides K.H. GBR AM J OBSTET GYNECOL 1993 168/I I (88-94) Objective: Our purpose was to investigate the relationship between fetal plasma erythropoietin concentration and measures of short-term and long-term glycemic control and fetal oxygenation in pregnancies complicated by maternal diabetes mellitus. Study design: A cross-sectional study was performed at The Harris Birthright Research Centre for Fetal Medicine, London. Cordocentesis was performed in 31 diabetic pregnanInt J Gynecol Obstet 43
cies for the measurement of umbilical venous blood pH, PO2, PcoZ, lactate and glucose concentration, erythroblast count, hemoglobin, and plasma erythropoietin concentrations. Results: The mean pH was significantly lower and the Pcq, lactate, erythropoietin, hemoglobin, and erythroblast counts were significantly higher than the appropriate normal mean for gestation. There were significant associations between (I) fetal erythropoietin and erythroblast count, (2) fetal erythroblast count and hemoglobin, (3) fetal hemoglobin and maternal glycosylated hemoglobin, and (4) maternal glucose and fetal glucose, pH, and lactate. Conclusions: We postulate that maternal hyperglycemia causes fetal hyperglycemia and acidemia. Increased erythropoietin may be caused by tissue hypoxia or hyperinsulinemia. The increase in fetal hemoglobin may be the consequence of increased erythropoiesis, mediated by either erythropoietin or hyperinsulinemia. Secretion of prostanoids by platelets and monocytes in normal and hypertensive pregnancies
Hawkins T.; Jones M.P.; Gallery E.D.M. AUS AM J OBSTET GYNECOL 1993 16812(661-667) Objectives: Secretory products of immune cells may induce or potentiate coagulation disturbances and vasoconstriction, both central features of pregnancy-induced hypertension. Women with chronic essential hypertension are at high risk of superimposed pregnancy-induced hypertension. The aim of our study was to compare secretory rates of prostanoids (active in coagulation and vascular reactivity) by peripheral blood monocytes and platelets from nonpregnant controls and from women in the third trimester of pregnancy, normals and those with either pregnancy-induced hypertension or uncomplicated chronic essential hypertension. Study design: From 100 ml blood, peripheral blood monocytes and platelets were isolated; their relative rates of in vitro production of prostacyclin, prostaglandin E,, and thromboxane were measured, and responses to stimulation by arachidonic acid or the calcium ionophore A23187 were compared among the four groups of subjects. Results: Basal peripheral blood monocyte secretory levels of prostanoids were low in all groups, with responses to both stimuli. Cells from women with chronic essential hypertension had a relatively exaggerated rise in thromboxane secretion (and to a lesser extent, prostacyclin) in response to the stimuli used, with a similar but less marked trend for those with pregnancy-induced hypertension. Platelets from women with chronic essential hypertension had particularly high basal secretory levels of thromboxane, with little further response to stimulation by arachidonic acid or A23187. Conclusions: Our work demonstrates clearly for the first time that peripheral blood monocytes from pregnant women secrete low levels of vasoactive prostanoids and respond to the stimuli used in a manner similar to that of nonpregnant women, and that cells from pregnant women with hypertension have a tendency to increased reactivity that is most marked in those with chronic essential hypertension. Platelets from women with chronic essential hypertension secrete near-maximal amounts of throm-
91
Citations from the Literature
This is a selection of abstracts taken from the literature in the field of obstetrics and gynecology which the Journal’s Editors feel may be of interest to our readers*
DISEASES IN PREGNANCY PIateIet4tetiv8ting factor mmotedved~eprlplnndcs
-
acetylbydrolase
activity
in
Maki N.; Magness R.R.; Miyaura S.; Gant N.F.; Johnston J.M. USA AM J OBSTET GYNECOL 1993 168/l I (50-54) Objective: The purpose of our study was to evaluate the hypothesis that pregnancy is associated with decreased plateletactivating factor-acetylhydrolase activity in women with normote&on, but not in women with hypertension. Study design: We evaluated plasma platelet-activating factor-acetylhydrolase activity in normal nonpregnant women (n = lo), normal pregnant women (n = 24), pregnant women with pregnancyinduced hypertension-preeclampsia (n = 7), and a group of men with normotension (n = 10). Results: Platelet-activating factoracetylhydrolase activity was lower at 32 weeks of gestation during normal pregnancies compared with nonpregnant controls (P < 0.001); however, in women with pregnancy-induced hypertension-preeclampsia, platelet-activating factor-acetylhydrolase activity was not decreased. Platelet-activating factoracetylhydrolase activity in men was higher than in all women (P < 0.01). Conclusion: Pregnant women with normotension may be refractory to pressor agents such as angiotensin II in part because of the decrease in plasma platelet-activating factor-acetylhydrolase activity, which results in an increase in platelet-activating factor. In contrast, enxyme activity is not decreased in pregnant women with hypertension, who have increased sensitivity to various pressor agents. Lowdose aapirIa In preventIon and treatment of intr8tine growth retud8tion and pregmncy-indmced hypertedon
Paraxzini F.; Benedetto C.; Frusca T.; Gregorini G.; Bocciolone L.; Marozio L.; Romero M.; Danesino V.; De Gaetano G.; Gastaidi A.; Massobrio M.; Remuxxi G.; Tognoni G.; Guaschino S.; Bianchi C.; Valcamonico A.; Giambuxxi M.; Ammendola D.; Casucci F.; et al.
*Generated from the Excerpta Medica Database, EMBASE.
ITA LANCET 1993 34118842(396-400) Meta-analysis of data from several controlled trials has shown that lowdose aspirin reduces the risk of pregnancyinduced hypertension (PHI) and intrauterine growth retardation (IUGR) in women at high risk of these disorders. We have asses& the etlicacy of low-dose aspirin in women judged to be at moderate risk. Women were included on prophylactic criteria - age under 18 or over 40 years, mild or moderate chronic hypertension (diastolic pressure between 90 and 110 mm Hg), nephropathy with normal renal function and blood pressure, history of PIH or IUGR, and twin pregnancy - or therapeutic criteria - PIH or early signs of IUGR in current pregnancy. Eligible women were randomly assigned treatment with 50 mg aspirin daily until delivery (583) or no treatment (523); 18 and 46 women, respectively, were lost to follow-up. The groups were well matched for baseline characteristics. We found no differences between the no-treatment and aspirin groups in numbers of spontaneous (5 vs. 2) or therapeutic (1 vs. 2) abortions, stillbirths (14 vs. 13), perinatal mortality (35.7 vs. 28.6 per 1000 births), mean birthweight (2858 [SD 7291vs. 2874 17951g), proportion of infants with birthweights below the 10th centile (95 [18.3%] vs. 117 [19.0%]), or births before 37 weeks’ gestation (184 [35.6%] vs. 209 [33.9%]). Nor did the groups differ in the frequency of PIH with or without proteinuria (51 [15.2%] vs. 81 [19.3%]). There was no difference in mean birthweight between the treatment groups in separate analyses according to criteria for trial entry and week of gestation at randomization. Our study gives little support to the notion that low-dose aspirin is beneficial in women at moderate risk of PIH or IUGR. FetaI pIasma erytbopoietin
conceetration
in severe growth
refdathm
Snijders R.J.M.; Abbas A.; Melby 0.; Ireland R.M.; Nicolaides K.H. GBR AM J OBSTET GYNECOL 1993 168/2 (615-619) Objective: The aim of this study was to determine whether hypoxemia induces an increase in plasma erythropoietin concentration in human fetal life and, if so, whether this response stimulates fetal erythropoiesis. Study design: The plasma Int J Gynecol Obsret 43
92
Citations from the Literature
erythropoietin concentration in blood samples from 33 smallfor-gestational-age fetuses at 26 to 38 weeks’ gestation was measured. Measurements were compared with the reference range for gestation, and associations with Po2, pH, and erythroblast and erythrocyte counts were examined. Results: The mean plasma erythropoietin concentration in the smallfor-gestational-age fetuses was significantly increased, and the degree of increase was significantly associated both with fetal acidemia and, more strongly, with fetal erythroblastosis. Conclusion: Erythropoietin production in response to tissue hypoxia occurs from at least 26 weeks’ gestation with measurable physiologic effects on erythropoiesis. Furthermore, more accurate assessment of tissue oxygenation may be obtained by measuring the erythroblast count rather than the blood pH.
Lowdose aspirin in the prevention of preeclampsia and fetal growth retardation: Rationale, mechanisms, and clinical trials
Dekker G.A.; Sibai B.M. USA AM J OBSTET GYNECOL 1993 168/l 1(214-227) Preeclampsia is characterized by a functional imbalance between vascular prostacyclin and thromboxane A2 production. On the basis of the hypothesis that preeclampsia is at least partially caused by an increase in thromboxane AZ, some studies attempted to correct this pathologic condition by pharmacologic manipulation with low-dose aspirin. The current literature suggests that the use of low-dose aspirin during pregnancy is safe with regard to congenital anomalies and fetal, neonatal, and maternal cardiovascular physiologic state and hemostasis. Aspirin at least partially corrects the pathologic increase in angiotensin II sensitivity that precedes the clinical development of preeclampsia. In addition, some clinical trials have demonstrated that low-dose aspirin is effective in reducing the incidence of preeclampsia and/or fetal growth retardation in selected high-risk women. Currently, large clinical trials are in progress to evaluate the effectiveness and side effects of the use of low-dose aspirin in preventing preeclampsia and/or fetal growth retardation. Until these studies have been completed, it will remain unclear whether antiplatelet therapy, such as lowdose aspirin, should be adopted for the prevention of either preeclampsia or fetal growth retardation. Fetal plasma erythropoietin in pregnancies complicated by maternal diabetes mellitus
Salvesen D.R.; Brudenell J.M.; Snijders R.J.M.; Ireland R.M.; Nicolaides K.H. GBR AM J OBSTET GYNECOL 1993 168/I I (88-94) Objective: Our purpose was to investigate the relationship between fetal plasma erythropoietin concentration and measures of short-term and long-term glycemic control and fetal oxygenation in pregnancies complicated by maternal diabetes mellitus. Study design: A cross-sectional study was performed at The Harris Birthright Research Centre for Fetal Medicine, London. Cordocentesis was performed in 31 diabetic pregnanInt J Gynecol Obstet 43
cies for the measurement of umbilical venous blood pH, PO2, PcoZ, lactate and glucose concentration, erythroblast count, hemoglobin, and plasma erythropoietin concentrations. Results: The mean pH was significantly lower and the Pcq, lactate, erythropoietin, hemoglobin, and erythroblast counts were significantly higher than the appropriate normal mean for gestation. There were significant associations between (I) fetal erythropoietin and erythroblast count, (2) fetal erythroblast count and hemoglobin, (3) fetal hemoglobin and maternal glycosylated hemoglobin, and (4) maternal glucose and fetal glucose, pH, and lactate. Conclusions: We postulate that maternal hyperglycemia causes fetal hyperglycemia and acidemia. Increased erythropoietin may be caused by tissue hypoxia or hyperinsulinemia. The increase in fetal hemoglobin may be the consequence of increased erythropoiesis, mediated by either erythropoietin or hyperinsulinemia. Secretion of prostanoids by platelets and monocytes in normal and hypertensive pregnancies
Hawkins T.; Jones M.P.; Gallery E.D.M. AUS AM J OBSTET GYNECOL 1993 16812(661-667) Objectives: Secretory products of immune cells may induce or potentiate coagulation disturbances and vasoconstriction, both central features of pregnancy-induced hypertension. Women with chronic essential hypertension are at high risk of superimposed pregnancy-induced hypertension. The aim of our study was to compare secretory rates of prostanoids (active in coagulation and vascular reactivity) by peripheral blood monocytes and platelets from nonpregnant controls and from women in the third trimester of pregnancy, normals and those with either pregnancy-induced hypertension or uncomplicated chronic essential hypertension. Study design: From 100 ml blood, peripheral blood monocytes and platelets were isolated; their relative rates of in vitro production of prostacyclin, prostaglandin E,, and thromboxane were measured, and responses to stimulation by arachidonic acid or the calcium ionophore A23187 were compared among the four groups of subjects. Results: Basal peripheral blood monocyte secretory levels of prostanoids were low in all groups, with responses to both stimuli. Cells from women with chronic essential hypertension had a relatively exaggerated rise in thromboxane secretion (and to a lesser extent, prostacyclin) in response to the stimuli used, with a similar but less marked trend for those with pregnancy-induced hypertension. Platelets from women with chronic essential hypertension had particularly high basal secretory levels of thromboxane, with little further response to stimulation by arachidonic acid or A23187. Conclusions: Our work demonstrates clearly for the first time that peripheral blood monocytes from pregnant women secrete low levels of vasoactive prostanoids and respond to the stimuli used in a manner similar to that of nonpregnant women, and that cells from pregnant women with hypertension have a tendency to increased reactivity that is most marked in those with chronic essential hypertension. Platelets from women with chronic essential hypertension secrete near-maximal amounts of throm-