Pregnancy-induced Hypertensive Disease Research Articles

Placental localization and expression of the cell death factors BNip3 and Nix in preeclampsia, intrauterine growth retardation and HELLP syndrome

Objective: BNip3 and its homologue Nix are pro-apoptotic factors of the Bcl-2-family and are expressed in malignant tumors. In vitro, this expression was shown to be mediated by hypoxia. Recently, it has been shown that placental hypoxia as well as apoptosis are pathogenetic factors for pregnancy-induced hypertensive diseases and intrauterine growth retardation (IUGR). The aim of the study was to analyze placental expression of BNip3 and Nix in pregnancies complicated by preeclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and IUGR. Material and methods: Placental tissue was sampled from 10 pregnancies each with preeclampsia, HELLP syndrome, IUGR and gestational age-matched controls. The placental expression of BNip3/Nix has been investigated with immunohistochemistry by the use of specific human BNip3/Nix antibodies. Results: In cytotrophoblastic cells, the BNip3 expression was strong in the control placentas, but only mediate in the placentas from pregnancies with preeclampsia, IUGR or HELLP syndrome. The intensity of the Nix staining showed a similar pattern. In the syncytiotrophoblast, there was a weak BNip3 staining observable in the control as well as IUGR samples, whereas BNip3 was undetectable in preeclamptic placentas or those with HELLP syndrome. For Nix, only in the preeclampsia a weak staining was detectable, whereas all other probes were negative. Conclusions: Our study shows for the first time that the pro-apoptotic proteins BNip3 and Nix are expressed in the human placenta. Pregnancies with placental dysfunction and hypertensive pregnancy disorders with different clinical manifestations are characterized by a significantly decreased expression of BNip3 and Nix. These results suggest that the hypothesis of generally increased placental apoptosis in pregnancy-induced hypertensive disorders caused by disturbed trophoblast invasion has to be partly reconsidered.

Women with schizophrenia: pregnancy outcome and infant death among their offspring

Schizophrenia in the mother may imply an increased risk of adverse pregnancy outcome. However, inconclusive findings, unknown pathological mechanisms and possible confounding by social factors and smoking requests further explorations. The aim of this study were to (1) examine non-optimal pregnancy outcome using data from a population-based cohort, controlling for covariates known to influence fetal growth; and (2) perform separate analyses of women diagnosed before childbirth and women hospitalized for schizophrenia during pregnancy. The study sample comprised 2096 births by 1438 mothers diagnosed with schizophrenia (of whom 696 mothers were antenatal diagnosed and 188 admitted during pregnancy) and 1,555,975 births in the general population. We found significantly increased risks for stillbirth, infant death, preterm delivery, low birth weight, and small-for-gestational-age among the offspring of women with schizophrenia. Women with an episode of schizophrenia during pregnancy had the highest risks (e.g., low birth weight; OR 4.3, 95% CI 2.9–6.6 and stillbirth; OR 4.4, 95% CI 1.4–13.8). Controlling for a high incidence of smoking during pregnancy among schizophrenic women (51% vs. 24% in the normal population) and other maternal factors (single motherhood, maternal age, parity, maternal education, mothers' country of birth and pregnancy-induced hypertensive diseases) in a multiple regression model, reduced the risk estimates markedly. However, the risks for adverse pregnancy outcomes were even after adjustments generally doubled for women with an episode of schizophrenia during pregnancy compared to women in the control group (e.g., low birth weight; OR 2.3, 95% CI 1.5–3.5, preterm delivery; OR 2.4, 95% CI 1.5–3.8 and stillbirth; OR 2.5, 95% CI 0.8–7.9). The risks for preterm delivery and low birth weight were significantly elevated throughout the analyses. We conclude that schizophrenia in the mother implies an increased risk for poor perinatal outcome, not fully explained by maternal factors, and a need to consider a common familial (probably genetic) vulnerability for pre- and perinatal stress and schizophrenia.

Placental abruption and perinatal death.

Studies of risk factors for abruptio placentae (AP) are partly conflicting and studies of risk factors for perinatal death in these pregnancies are scarce. Using the population-based Swedish Birth Registry from 1987 to 1993, we were able to study these risks in 795,459 singleton pregnancies. Logistic regression analysis was used to estimate odds ratios (OR) for risk of AP and risk of perinatal death in pregnancies with and without AP. Risk factors for AP were: age, primiparity, high parity, not cohabiting with infant's father, low education, smoking, infertility, pregestational diabetes, essential hypertension, pregnancy-induced hypertensive diseases, preterm premature rupture of membranes, preterm birth and small-for-gestational-age (SGA) births. Risk factors for perinatal death in pregnancies with placental abruption were smoking (1--9 and > or =10 cigarettes/day; OR 1.4 and 1.7 respectively), severe pre-eclampsia (OR 2.0) and SGA (OR 1.9), whereas in pregnancies without abruption, risks were also increased in maternal age > or =35 years, primiparity, infertility, essential hypertension and pregestational diabetes. These findings support the theory that, in cases of AP, a general impairment of the placenta and/or a defect placentation may be fatal.

Genetic effects on the liability of developing pre-eclampsia and gestational hypertension

Genetic factors are known to be important in the etiology of pre-eclampsia and possibly also gestational hypertension, but the degree of genetic influence has not been quantified. To estimate the genetic and environmental effects on the liability of developing pre-eclampsia and gestational hypertension, we cross-linked the population-based Swedish Twin Register and the Swedish Medical Birth Register. We included female twin pairs with known zygosity, both of whom gave birth in Sweden from 1973 through 1993; in all 917 monozygotic and 1,199 dizygotic twin pairs. For pre-eclampsia, the estimates of heritability and nonshared environmental effect were 0.54 (95% confidence interval 0–0.71) and 0.46 (0.29–0.67), respectively; corresponding estimates for gestational hypertension were 0.24 (0–0.53) and 0.76 (0.47–1.00), respectively. When considering both diseases as a single entity (pregnancy-induced hypertensive diseases), the heritability estimate was 0.47 (0.13–0.61). These results suggest that genetic factors are important in the development of pre-eclampsia as well as gestational hypertension. The heritability estimates can be of importance when planning genetic linkage studies. In efforts to identify women with elevated risk of developing pre-eclampsia during pregnancy, a question about family history of pre-eclampsia should be included. Am. J. Med. Genet. 91:256–260, 2000. © 2000 Wiley-Liss, Inc.

Genetic effects on the liability of developing pre-eclampsia and gestational hypertension

Genetic factors are known to be important in the etiology of pre-eclampsia and possibly also gestational hypertension, but the degree of genetic influence has not been quantified. To estimate the genetic and environmental effects on the liability of developing pre-eclampsia and gestational hypertension, we cross-linked the population-based Swedish Twin Register and the Swedish Medical Birth Register. We included female twin pairs with known zygosity, both of whom gave birth in Sweden from 1973 through 1993; in all 917 monozygotic and 1,199 dizygotic twin pairs. For pre-eclampsia, the estimates of heritability and nonshared environmental effect were 0. 54 (95% confidence interval 0-0.71) and 0.46 (0.29-0.67), respectively; corresponding estimates for gestational hypertension were 0.24 (0-0.53) and 0.76 (0.47-1.00), respectively. When considering both diseases as a single entity (pregnancy-induced hypertensive diseases), the heritability estimate was 0.47 (0.13-0. 61). These results suggest that genetic factors are important in the development of pre-eclampsia as well as gestational hypertension. The heritability estimates can be of importance when planning genetic linkage studies. In efforts to identify women with elevated risk of developing pre-eclampsia during pregnancy, a question about family history of pre-eclampsia should be included.

Does labetalol predispose to pulmonary edema in severe pregnancy-induced hypertensive disease?

We investigated whether use of labetalol, a beta adrenoreceptor blocking antihypertensive agent commonly employed as an alternative to hydralazine, is independently associated with pulmonary edema in women with severe preeclampsia. We retrospectively evaluated women with severe preeclampsia who were given labetalol by intravenous bolus for MAP > 120 mm Hg. Outcome variables included: achieving MAP < 120 mm Hg with < 300 mg of labetalol, incidence of adverse effects of the drug, including pulmonary edema, hypotension, and maternal bradycardia. Total intravenous fluid intake exceeding output (+ delta I/O) and presence or absence of preeclamptic liver involvement were noted. Statistical analysis included unpaired t-tests and Fisher's exact test. Fifty-one women were studied, 7 (13.7%) of whom developed pulmonary edema. Demographic and pregnancy characteristics were not different between patients who did or did not develop pulmonary edema. No patient had detectable underlying heart disease. Patients with or without pulmonary edema did not differ as regards entry MAP (130 +/- 14 vs. 129 +/- 18 mm Hg), total dose of labetalol (209 +/- 83 vs. 193 +/- 39 mg/24 hours), incidence of bradycardia or hypotension (0/7 vs. 8/44), or presence of hepatic involvement (1/7 vs. 9/44). However, there was a significant difference in degree of positive fluid balance. Patients developing pulmonary edema had a net gain of 1,466 +/- 429 mL of fluid in the 24 hours in which they received labetalol than those who did not (659 +/- 1152 mL, P = .003). Initial central hemodynamic monitoring data revealed no impairment of cardiac performance (mean cardiac output 7.7 +/- 1.8 L/min, cardiac index 4.0 +/- 0.8 L/min/m2, left ventricular stroke work index 73 +/- 9 g.m.m-2) despite high pulmonary capillary wedge pressures (22 +/- 4 mm Hg). We conclude that the incidence of pulmonary edema in patients with severe preeclampsia who are treated with labetalol appears to be a result of an increase in third space fluid accumulation as a manifestation of the severity of their disease, not a direct effect of the drug on cardiac performance.

Does labetalol predispose to pulmonary edema in severe pregnancy-induced hypertensive disease?

We investigated whether use of labetalol, a beta adrenoreceptor blocking antihypertensive agent commonly employed as an alternative to hydralazine, is independently associated with pulmonary edema in women with severe preeclampsia. We retrospectively evaluated women with severe preeclampsia who were given labetalol by intravenous bolus for MAP >120 mm Hg. Outcome variables included: achieving MAP < 120 mm Hg with < 300 mg of labetalol, incidence of adverse effects of the drug, including pulmonary edema, hypotension, and maternal bradycardia. Total intravenous fluid intake exceeding output (+delta I/O) and presence or absence of preeclamptic liver involvement were noted. Statistical analysis included unpaired t-tests and Fisher's exact test. Fifty-one women were studied, 7 (13.7%) of whom developed pulmonary edema. Demographic and pregnancy characteristics were not different between patients who did or did not develop pulmonary edema. No patient had detectable underlying heart disease. Patients with or without pulmonary edema did not differ as regards entry MAP (130 ± 14 vs. 129 ± 18 mm Hg), total dose of labetalol (209 ± 83 vs. 193 ± 39 mg/24 hours), incidence of bradycardia or hypotension (0/7 vs. 8/44), or presence of hepatic involvement (1/7 vs. 9/44). However, there was a significant difference in degree of positive fluid balance. Patients developing pulmonary edema had a net gain of 1,466 ± 429 mL of fluid in the 24 hours in which they received labetalol than those who did not (659 ± 1152 mL, P =. 003). Initial central hemodynamic monitoring data revealed no impairment of cardiac performance (mean cardiac output 7.7 ± 1.8 L/min, cardiac index 4.0 ± 0.8 L/min/m2, left ventricular stroke work index 73 ± 9 g.m.m-2) despite high pulmonary capillary wedge pressures (22 ± 4 mm Hg). We conclude that the incidence of pulmonary edema in patients with severe preeclampsia who are treated with labetalol appears to be a result of an increase in third space fluid accumulation as a manifestation of the severity of their disease, not a direct effect of the drug on cardiac performance.

Pregnancy-induced hypertension and hyaline membrane disease

Objectives: (1) To determine whether the incidence of hyaline membrane disease (HMD) is different among premature babies of pre-eclamptic women and those of normotensive controls; (2) to determine the relative risk (RR) of HMD according to the severity of pre-eclampsia and gestational age. Methods: A retrospective and prospective cohort of 271 pre-eclamptic women and 271 normotensive controls, with gestational age between 28 and 34 weeks was studied, including only singleton pregnancies, live fetuses and well-documented gestational age. Exclusion criteria were ruptured membranes > 24 h, other maternal diseases and previous use of corticosteroids. Statistical analysis included relative risk and multiple logistic regression model. Results: The RR of HMD for babies of pre-eclamptic women was 0.96 (95% CI: 0.78–1.17), and remained unchanged after controlling for gestational age and multiple logistic regression analysis. Conclusion: Preterm babies of pre-eclamptic mothers had the same probability of having HMD as newborns of normotensive mothers.

Intrauterine eicosanoid production in uncomplicated and hypertensive pregnancies: alterations of placental 12-hydroxyeicosatetraenoic acid.

Complicating about 10% of all pregnancies pregnancy-induced hypertensive diseases account for an enormous number of maternal deaths. At present, termination of pregnancy represents the only treatment of the cause. The important role of eicosanoids in pregnancy-induced hypertension is generally accepted1–2. As humoral vasoactive factors they are important for vascular tone regulation of the non-innervated uteroplacental vessels. In PIH and related diseases, these vessels fail to dilate normally, leading to a chronic preplacental decrease in circulation. A systemic lack of prostacyclin may also promote an increased vasoconstriction and coagulation disturbances in PIH leading to endothelial cell disorder, hemolysis and the vicious circle of disseminated intravasai coagulation3–4.KeywordsFetal MembraneTrophoblastic InvasionEicosanoid ProductionRadioactivity DetectionEpoxyeicosatrienoic AcidThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Hemostatic abnormalities may predict chronic hypertension after preeclampsia.

Preeclampsia is a pregnancy-induced hypertensive disease. About 25-30% of women suffering from this disease will later, while still fertile, develop essential hypertension. Various hemostatic variables known to increase the risk of cardiovascular complications were investigated in 28 women with severe preeclampsia and 14 with mild preeclampsia 6-15 months after delivery. High levels of the coagulation inhibitors protein C and total protein S were found in the women with severe preeclampsia (p < 0.001). The levels of prothrombin complex, fibrinogen, plasminogen activator inhibitor-1 were increased in women who had previously had severe preeclampsia as compared to those who had had mild preeclampsia (p < 0.01). The levels of the four markers for thrombin activity (thrombin-antithrombin complex, prothrombin fragments 1 + 2, fibrin D-dimers and soluble fibrin) were higher in the severe preeclampsia group. In 12 women in this group (43%), the levels of three to four variables were higher than the reference ranges (mean +/- 2 SD). In patients with earlier severe or mild preeclampsia, factor VII antigen was also found to be increased as compared to normal fertile women (p < 0.02). Women with earlier severe preeclampsia displayed increased levels of coagulation factors and the main fibrinolytic inhibitor, high levels of which are known to predict cardiovascular events. This was also reflected by increased levels of thrombin markers.

The role of complement in pregnancy-induced hypertensive disease

Preeclampsia is a pregnancy-induced hypertensive disease with an incidence of about 5% in primigravidas and, being common, it significantly contributes to maternal and neonatal morbidity and mortality. The primary cause remains unknown but might be immunologic, since immunologic aberrations are described in preeclampsia. Activation of the complement system in pregnancy-induced hypertensive disease has been discussed during the last 60 years. It is now strongly indicated that complement activation occurs in preeclampsia. The complement system is very potent and one of the major effector pathways of the process of inflammation. The pathological manifestations, endothelial damage and microvascular injury, and thereby the clinical findings in preeclampsia, may be explained by complement activation, resulting in the direct vascular effects of biological active complement components and complement-mediated activation of leukocytes, with release of potent inflammatory mediators. This new etiological hypothesis might give other options in therapy and prevention of pregnancy-induced hypertensive disease.

Use of Antithrombotic Agents During Pregnancy

Anticoagulant therapy is indicated during pregnancy for the prevention and treatment of venous thromboembolism and for the prevention and treatment of systemic embolism in patients with prosthetic heart valves and other valvular heart disorders. Aspirin is effective in reducing complications associated with pregnancy-induced hypertensive disease and may be effective in combination with prednisone for the prevention of fetal loss associated with the presence of APLA. Several questions concerning anticoagulant therapy remain unanswered. Although it is highly likely that heparin therapy is safe for the fetus, the true risk of clinically important maternal osteoporosis after long-term heparin is unknown. Oral anticoagulants are fetopathic, but the true risks of the warfarin embryopathy and central nervous system abnormalities are unknown. There is some evidence that warfarin embryopathy occurs only when oral anticoagulants are administered between 6 and 12 weeks of gestation and that oral anticoagulants may not be fetopathic when administrated in the first 6 weeks of gestation. 9 The fetal risks are probably lower after the 12th week of gestation than between the 6th and 12th weeks, but warfarin is probably still fetopathic when administered during the 2nd and 3rd trimesters. Oral anticoagulant therapy should be avoided in the weeks before delivery because of the risk of serious perinatal bleeding caused by the trauma of delivery to the anticoagulated fetus. The safety of aspirin during the first trimester of pregnancy is still a subject of debate. In addition, it is not clear whether aspirin alone is effective for the prevention of fetal loss associated with APLA.

Group I and group II phospholipase A2 in serum during normal and pathological pregnancy.

Phospholipase A2 groups I (pancreatic) and II (synovial) could be a link between local and systemic changes in pregnancy, reflected in catalytic activity. We studied whether normal pregnancy, preeclampsia, preterm labor and four other diseases have processes involving serum phospholipase A2s. Pancreatic and synovial-type phospholipase A2 were measured in the serum of 59 normal pregnant women and 89 patients with pathological pregnancy by newly developed time-resolved fluoroimmunoassays, and the catalytic activity by a radiochemical method using micellar phosphatidylcholine as substrate. During pregnancy weeks 6-14, synovial-type phospholipase A2 and catalytic activity were elevated 2- to 4-fold, but at 37 weeks values were normal. Pregnancy-induced hypertensive diseases increased by 4- to 10-fold the concentration of synovial-type phospholipase A2, reflected in catalytic activity. In 8 out of 14 cases, the enzyme was increased if the fetus was to be delivered prematurely. The enzymes studied remained within the reference interval in cases of hepatogestosis, fetal asphyxia, diabetes and twin pregnancy. Newly developed specific immunoassays for measuring different types of phospholipase A2 in serum can provide insights for clinical follow-up.

Use of Antithrombotic Agents During Pregnancy

Anticoagulant therapy is indicated during pregnancy for the prevention and treatment of venous thromboembolism and for the prevention and treatment of systemic embolism in patients with prosthetic heart valves and other valvular heart disorders. Aspirin is effective in reducing complications associated with pregnancy-induced hypertensive disease and may be effective in combination with prednisone for the prevention of fetal loss associated with the presence of APLA. Several questions concerning anticoagulant therapy remain unanswered. Although it is highly likely that heparin therapy is safe for the fetus, the true risk of clinically important maternal osteoporosis after long-term heparin is unknown. Oral anticoagulants are fetopathic, but the true risks of the warfarin embryopathy and central nervous system abnormalities are unknown. There is some evidence that warfarin embryopathy occurs only when oral anticoagulants are administered between 6 and 12 weeks of gestation and that oral anticoagulants may not be fetopathic when administrated in the first 6 weeks of gestation. 9 Iturbe-Alessio I del Carmen Fonseca M Mutchinik O et al. Risks of anticoagulant therapy in pregnant women with artificial heart valves. N Engl J Med. 1986; 315: 1390-1393 Crossref PubMed Scopus (256) Google Scholar The fetal risks are probably lower after the 12th week of gestation than between the 6th and 12th weeks, but warfarin is probably still fetopathic when administered during the 2nd and 3rd trimesters. Oral anticoagulant therapy should be avoided in the weeks before delivery because of the risk of serious perinatal bleeding caused by the trauma of delivery to the anticoagulated fetus. The safety of aspirin during the first trimester of pregnancy is still a subject of debate. In addition, it is not clear whether aspirin alone is effective for the prevention of fetal loss associated with APLA. Anticoagulant therapy is indicated during pregnancy for the prevention and treatment of venous thromboembolism and for the prevention and treatment of systemic embolism in patients with prosthetic heart valves and other valvular heart disorders. Aspirin is effective in reducing complications associated with pregnancy-induced hypertensive disease and may be effective in combination with prednisone for the prevention of fetal loss associated with the presence of APLA. Several questions concerning anticoagulant therapy remain unanswered. Although it is highly likely that heparin therapy is safe for the fetus, the true risk of clinically important maternal osteoporosis after long-term heparin is unknown. Oral anticoagulants are fetopathic, but the true risks of the warfarin embryopathy and central nervous system abnormalities are unknown. There is some evidence that warfarin embryopathy occurs only when oral anticoagulants are administered between 6 and 12 weeks of gestation and that oral anticoagulants may not be fetopathic when administrated in the first 6 weeks of gestation. 9 Iturbe-Alessio I del Carmen Fonseca M Mutchinik O et al. Risks of anticoagulant therapy in pregnant women with artificial heart valves. N Engl J Med. 1986; 315: 1390-1393 Crossref PubMed Scopus (256) Google Scholar The fetal risks are probably lower after the 12th week of gestation than between the 6th and 12th weeks, but warfarin is probably still fetopathic when administered during the 2nd and 3rd trimesters. Oral anticoagulant therapy should be avoided in the weeks before delivery because of the risk of serious perinatal bleeding caused by the trauma of delivery to the anticoagulated fetus. The safety of aspirin during the first trimester of pregnancy is still a subject of debate. In addition, it is not clear whether aspirin alone is effective for the prevention of fetal loss associated with APLA.

Placental protein 12 (PP 12) in pregnancy-induced hypertensive diseases

Placental protein 12 (PP12) was measured in 30 patients with hypertensive disorders of pregnancy, 10 healthy pregnant and 10 healthy nonpregnant controls. Differences in PP12-concentrations of healthy nonpregnant (median 2.0 micrograms/l, range 1.0-5.5 micrograms/l) and healthy pregnant controls (median 110 micrograms/l, range 29-280 micrograms/l), as well as between healthy nonpregnant controls and hypertensive patients (median 125 micrograms/l, range 28-420 micrograms/l) were both statistically highly significant (p less than 0.001). The comparison between healthy pregnant and hypertensive women demonstrated no statistically significant differences. In coexistent intrauterine growth retardation (median 163 micrograms/l, range 60-400 micrograms/l), higher values could be observed in some patients, but this group showed no statistically significant difference compared to healthy pregnant controls with adequate fetal weight. PP12 does not seem to be a clinically usable parameter in the diagnosis of hypertensive disorders of pregnancy and fetal growth retardation, because of the widespread range of results.

A meta-analysis of low-dose aspirin for the prevention of pregnancy-induced hypertensive disease

International Journal of Gynecology & ObstetricsVolume 38, Issue 2 p. 152-152 Citations from the literature pregnancy and delivery A meta-analysis of low-dose aspirin for the prevention of pregnancy-induced hypertensive disease TF Imperiale, TF ImperialeSearch for more papers by this authorAS Petrulis, AS PetrulisSearch for more papers by this author TF Imperiale, TF ImperialeSearch for more papers by this authorAS Petrulis, AS PetrulisSearch for more papers by this author First published: June 1992 https://doi.org/10.1016/0020-7292(92)90079-XAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume38, Issue2June 1992Pages 152-152 RelatedInformation

Low-Dose Aspirin to Prevent Pregnancy-Induced Hypertensive Disease

To the Editor. —A Meta-analysis of Low-Dose Aspirin for Prevention of Pregnancy-Induced Hypertensive Disease, by Imperiale and Petrulis, 1 and A Multivariate Analysis of Risk Factors for Preeclampsia, by Eskenazi et al, 2 add to the growing knowledge 3,4 of the potential to improve pregnancy outcome with daily low-dose aspirin starting in the second trimester. The meta-analysis combines studies for preventing pregnancy-induced hypertension with those for preventing recurrent fetal growth retardation. An additional recent study by Uzan et al 5 provides more extensive data supporting prevention of fetal growth retardation with aspirin. Thus, thromboxane-induced placental insufficiency does not appear to be limited to pregnancies with hypertension. The published data suggest that pregnancy risk groups to be considered for low-dose aspirin include (1) primiparae, especially those who are black, and (2) women with ( a ) previous pre-eclampsia, ( b ) a history of previous fetal growth retardation not explained by other causes, and ( c

Low-dose aspirin to prevent pregnancy-induced hypertensive disease

Low-dose aspirin to prevent pregnancy-induced hypertensive disease

Low-Dose Aspirin to Prevent Pregnancy-Induced Hypertensive Disease

<h3>To the Editor.</h3> — Imperiale and Petrulis report a meta-analysis of the use of low-dose aspirin to prevent pregnancy-induced hypertensive disease.¹Despite a review of the English-language literature, they are apparently unaware of a similar meta-analysis first published by Collins in May 1988 and regularly updated subsequently.^2,3Unlike Imperiale and Petrulis, Collins excluded all nonrandomized studies since such studies may introduce a bias in the assessment of treatment. Similarly, because of concerns about the selection biases that might arise by reviewing only the published data, Collins included data from unpublished studies as well as seeking information from investigators about relevant outcome measures that had not been reported. Thus, 13 studies contribute to his latest analysis including the results of the largest trial the results of which were presented publicly in January 1990 and published recently.⁴ We would commend databases such as the Oxford Database of Clinical Trials³

Low-Dose Aspirin to Prevent Pregnancy-Induced Hypertensive Disease

<h3>To the Editor.</h3> —The recent meta-analysis of aspirin and pregnancy-induced hypertension by Imperiale and Petrulis¹caught our interest, and we examined this issue from the standpoint of clinical decision making. Since the meta-analysis included studies that were not randomized, not blinded, or used dipyridamole in addition to aspirin, we excluded data from those studies. Using data from the remaining studies that addressed cesarean sections,^2-4we found that 5.6% of the aspirin group required cesarean sections, compared with 23.9% of the control group. With a maximum aspirin cost of $4.60 and a cost difference between cesarean and vaginal birth of $3014,⁵the overall expected cost with aspirin is $173 per patient vs $720 without aspirin treatment. This indicates a significant cost saving by the reduction of cesarean births alone. Two concerns may alter this assessment. As mentioned in the meta-analysis, the indications for cesarean section were not uniformly