TherapeuticsNovember 1, 1999Review: Antihypertensive drugs improve maternal outcomes in mild chronic and pregnancy-induced hypertensionRobert Burrows, MDRobert Burrows, MDMonash University, Clayton, Victoria, Australia (R.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-1999-131-3-061 SectionsAboutFull Text ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinkedInRedditEmail Source CitationMagee LA, Ornstein MP, von Dadelszen P. Management of hypertension in pregnancy. BMJ. 1999 May 15;318:1332-6.References1 Helewa ME, Burrows RF, Smith J, et al. CMAJ. 1997;157:715-25. Google Scholar2 Mountquin JM, Garner PR, Burrows RF, et al. CMAJ. 1997;907-19. Google Scholar3 Rey E, LeLorier J, Burgess E, Lange IR, Leduc L. CMAJ. 1997;157:1245-54. Google Scholar4 Review: Pharmacologic treatment of hypertension during pregnancy reduces perinatal deaths and severe maternal hypertension. ACP J Club. 1998 May-Jun;128:63. Abstract of: CMAJ. 1997;157:1245-54. Google Scholar Author, Article, and Disclosure InformationAffiliations: Monash University, Clayton, Victoria, Australia (R.B.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails November 1, 1999Volume 131, Issue 3Page: 61KeywordsAdverse reactionsBradycardiaCesarean sectionClinical trialsDrug deliveryDrug therapyDrugsEclampsiaFetusesHemorrhageHospitalizationsHypertensionHypoglycemiaHypotensionInfantsInformation storage and retrievalMaternal mortalityMorbidityProteinuria ePublished: 9 March 2020 Issue Published: November 1, 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.Loading ...

Source Citation Sibai BM, Lindheimer M, Hauth J, et al., for the National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Risk factors for preeclampsia, abruptio placentae, and adverse neonatal outcomes among women with chronic hypertension. N Engl J Med. 1998 Sep 3;339:667-71.

Between the time of completion of our article and its publication (Burrows RF, Burrows EA. The feasibility of a control population for a randomized control trial of seizure prophylaxis in the hypertensive disorders of pregnancy. AM J OBSTET GYNECOL 1995;173:929-35), several more years of experience with nonseizure prophylaxis in the hypertensive disorders of pregnancy have occurred. In addition, several important studies on this issue have been published. First, the Eclampsia Trial Collaborative Group1Eclampsia Trial Collaborative Group Which anticonvulsant for women with eclampsia? Evidence from a collaborative eclampsia trial.Lancet. 1995; 345: 1455-1463PubMed Google Scholar did a randomized trial that showed that magnesium sulfate was superior to phenytoin and diazepam in the treatment of recurrent eclampsia, although with still a 5% to 10% failure rate. Although it may seem reasonable that treatment success in reducing the frequency of recurrent eclampsia should transmit to prophylaxis success, this assumption is unjustified without further documentation that it is indeed true. The randomized nonblinded trial of Lucas et al.2Lucas MJ Leveno KJ Cunningham FG A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia.N Engl J Med. 1995; 333: 201-205Crossref PubMed Scopus (476) Google Scholar was published in The New England Journal of Medicine. This study of seizure prophylaxis in pregnancy-induced hypertension, both nonproteinuric and proteinuric, unfortunately did not have nontreatment controls but compared magnesium sulfate with phenytoin. It suggested that magnesium sulfate was superior to phenytoin in seizure prophylaxis. The randomized trial of Moodley and Moodley3Moodley J Moodley VV Prophylactic anticonvulsant therapy in hypertensive crisis of pregnancy - the need for a large randomized trial.Hypertens Pregnancy. 1995; 13: 245-252Crossref Scopus (40) Google Scholar compared management of preeclampsia with antihypertensives with management of preeclampsia with antihypertensives and magnesium sulfate. The authors showed that magnesium sulfate did not contribute to a further reduction in seizure occurrence. Given that all patients entered in the study by Lucas et al. had pregnancy-induced hypertension (new onset after 20 weeks' gestation) and given that they are likely similar to our patients, some comparisons can be made between their therapy arms and our nontherapy arm (Table I). Table IComparison of phenytoin and magnesium sulfate prophylaxis2 with our population having no seizure prophylaxisPhenytoinMagnesium sulfateControlGestational hypertension without proteinuria4/891 0.5% (0.1%-1.1%)*0/846 0.0% (0.0%-0.4%)*1/860 0.1% (0.01%-0.6%)*Gestational hypertension with proteinuria6/198 3.0% (1.1%-6.5%)†0/203 0.0% (0.0%-1.8%)‡17/450 3.8% (2.2%-6.0%)Values indicate 95% confidence intervals.*Magnesium sulfate versus phenytoin, magnesium sulfate versus control, and phenytoin versus control, not significant.†Phenytoin versus magnesium sulfate, p = 0.04; phenytoin versus control, not significant.‡Magnesium sulfate versus control, p = 0.01. Open table in a new tab Values indicate 95% confidence intervals. *Magnesium sulfate versus phenytoin, magnesium sulfate versus control, and phenytoin versus control, not significant. †Phenytoin versus magnesium sulfate, p = 0.04; phenytoin versus control, not significant. ‡Magnesium sulfate versus control, p = 0.01. In gestational hypertension (pregnancy-induced hypertension without proteinuria) there was no significant difference in seizure occurrence between phenytoin and magnesium sulfate or between either of these agents and controls. Seizure prophylaxis of nonproteinuric hypertension with either agent appears to offer no benefit over no prophylactic antiseizure therapy. In the preeclamptic group comparison of the phenytoin and magnesium sulfate groups shows a p value of 004 in favor of magnesium sulfate; however, the 95% confidence interval overlap suggests that the premature termination of this study may be leading us to a type I error. Note that merely one seizure in the magnesium sulfate group (with this sample size) would result in a nonsignificant p value of 0.1. In comparing the magnesium sulfate group with our control group, examination shows that there is no cross-over of 95% confidence interval and p = 001. However, the groups may not be as comparable as suggested, because the platelet counts <100 × 109/L were seen in only 5.5% of the magnesium sulfate group, whereas our rate was 14%, suggesting that our patients may have been sicker and therefore had a greater baseline seizure risk. In addition, by the formula of Hanley and Lippman-Hand4Hanley JA Lippman-Hand A If nothing goes wrong, is everything alright?.JAMA. 1983; 259: 1743-1745Crossref Scopus (1109) Google Scholar (to determine the probability of an adverse or undesirable event during an intervention that has not yet occurred in a finite number of patients), the upper limit of the 95% confidence interval for the number of seizures that could have occurred in the cohort of 203 patients treated with magnesium sulfate is 2; this would give a p value of 007 compared with our controls. Further evidence that the issue of prophylaxis is not yet settled in favor of magnesium sulfate is provided by Moodley and Moodley3Moodley J Moodley VV Prophylactic anticonvulsant therapy in hypertensive crisis of pregnancy - the need for a large randomized trial.Hypertens Pregnancy. 1995; 13: 245-252Crossref Scopus (40) Google Scholar (Table II). Combining this data with that acknowledged of Odendaal and Hale5Odendaal HJ Hale D Is magnesium sulfate really necessary to prevent eclampsia in patients with severe preeclampsia? [Abstract 149].in: Proceedings of the ninth international congress of the International Society for the Study of Hypertension in Pregnancy, Sydney, Australia, March 15-18, 1994. International Society for the Study of Hypertension in Pregnancy, Sydney1994Google Scholar in our paper demonstrate that no additional benefit is offered to preeclamptic patients treated with antihypertensives by the addition of magnesium sulfate prophylaxis. Further evidence of this is obtained from our population, where the rate of seizures in preeclamptic patients treated with antihypertensives (342) was 3.2% with a 95% confidence interval of 1.6% to 5.7%, confidence limits that overlap those seen in the study of Lucas et al.2Lucas MJ Leveno KJ Cunningham FG A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia.N Engl J Med. 1995; 333: 201-205Crossref PubMed Scopus (476) Google Scholar for magnesium sulfate prophylaxis in preeclampsia (0.0% to 1.8%, Table I). Table IIComparison of seizure rates in two studies randomizing preeclamptic patients to blood pressure treatment only or blood pressure treatment and magnesium sulfateOdendaal and Hale5Odendaal HJ Hale D Is magnesium sulfate really necessary to prevent eclampsia in patients with severe preeclampsia? [Abstract 149].in: Proceedings of the ninth international congress of the International Society for the Study of Hypertension in Pregnancy, Sydney, Australia, March 15-18, 1994. International Society for the Study of Hypertension in Pregnancy, Sydney1994Google ScholarMoodley and Moodley3Moodley J Moodley VV Prophylactic anticonvulsant therapy in hypertensive crisis of pregnancy - the need for a large randomized trial.Hypertens Pregnancy. 1995; 13: 245-252Crossref Scopus (40) Google ScholarTotalBlood pressure medications3/509 0.6% (0.1%-1.7%)0/116 0.0% (0.0%-3.1%)3/625 0.5% (0.1%-1.4%)Blood pressure medications + magnesium sulfate2/487 0.4% (005%-1.5%)1/112 0.9% (002%-4.9%)3/599 0.5% (0.1%-1.5%)No comparisons significant at p = 0.05. Open table in a new tab No comparisons significant at p = 0.05. It appears that no prophylactic therapy currently prevents seizures effectively in gestational hypertension (hypertension without proteinuria). The rate of seizure occurrence may be so low and unpredictable that the number needed to treat would be too high even if a therapy was proved effective. In preeclampsia (hypertension with proteinuria), evidence is weak for the effectiveness of phenytoin; however, because of the 95% confidence interval override in the study by Lucas et al.,2Lucas MJ Leveno KJ Cunningham FG A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia.N Engl J Med. 1995; 333: 201-205Crossref PubMed Scopus (476) Google Scholar an effect comparable to that of magnesium sulfate cannot be ruled out. The evidence for magnesium sulfate is stronger but not beyond doubt. The likelihood of a type I error in the article by Lucas et al.2Lucas MJ Leveno KJ Cunningham FG A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia.N Engl J Med. 1995; 333: 201-205Crossref PubMed Scopus (476) Google Scholar and given the evidence of Moodley and Moodley3Moodley J Moodley VV Prophylactic anticonvulsant therapy in hypertensive crisis of pregnancy - the need for a large randomized trial.Hypertens Pregnancy. 1995; 13: 245-252Crossref Scopus (40) Google Scholar and Odendaal et al.,5Odendaal HJ Hale D Is magnesium sulfate really necessary to prevent eclampsia in patients with severe preeclampsia? [Abstract 149].in: Proceedings of the ninth international congress of the International Society for the Study of Hypertension in Pregnancy, Sydney, Australia, March 15-18, 1994. International Society for the Study of Hypertension in Pregnancy, Sydney1994Google Scholar a trial of magnesium sulfate versus placebo is still needed. Both our article and those from South Africa provide the reassurance that a control population can be used ethically and safely. 6/8/70571

A previously healthy multigravida woman presenting with pyrexia was found to be pancytopenic at 32 weeks' gestation. The leukopenia and the thrombocytopenia responded to supportive therapy. The anemia, which was Coombs' negative, continued and was associated with a drop in fibrinogen, but both eventually returned to normal with time. The isolation of the cytomegalovirus and the detection of an IgM immune response to cytomegalovirus implicated the virus as the agent responsible for the clinical manifestations. The fetus, who was well throughout the maternal illness, had no evidence of anemia or thrombocytopenia at birth; however, intrauterine infection was confirmed by isolation of the virus from the newborn's urine.