A PROSPECTIVE CONTROLLED TRIAL OF METOPROLOL‐HYDRALAZINE TREATMENT IN HYPERTENSION DURING PREGNANCY Early blood pressure control improves pregnancy outcome in primigravid women with mild hypertension. l-Arginine supplementation in women with chronic hypertension: impact on blood pressure and maternal and neonatal complications FINAL REPORT OF STUDY ON HYPERTENSION DURING PREGNANCY: THE EFFECTS OF SPECIFIC TREATMENT ON THE GROWTH AND DEVELOPMENT OF THE CHILDREN Antihypertensive Drug Effects on Placental Flow Velocity Waveforms in Pregnant Women with Severe Hypertension A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy. EFFECT OF ANTIHYPERTENSIVE DRUGS ON NEONATAL BLOOD PRESSURE A comparative study of the use of epoprostenol and dihydralazine in severe hypertension in pregnancy. [Chronic high blood pressure in 110 pregnant women]. A randomized comparison of early with conservative use of antihypertensive drugs in the management of pregnancy‐induced hypertension FETAL OUTCOME IN TRIAL OF ANTIHYPERTENSIVE TREATMENT IN PREGNANCY The Effect of Prophylactic Management and Therapeutics on Hypertensive Disease in Pregnancy: Preliminary Studies A comparison of nifedipine with methyldopa in pregnancy induced hypertension. TREATMENT OF HYPERTENSION IN PREGNANCY WITH METHYLDOPA: BLOOD PRESSURE CONTROL AND SIDE EFFECTS Effect of exercise on blood pressure in pregnant women with a high risk of gestational hypertensive disorders. Short-term treatment of severe hypertension of pregnancy: prospective comparison of nicardipine and labetalol All Hypertensive Disorders of Pregnancy Increase the Risk of Future Cardiovascular Disease
Abstract . in an open , controlled trial , treatment with a combination of metoprolol and hydralazine was compared with non‐pharmacological management of mild and moderate hypertension in pregnancy . One hundred and sixty‐one women participated in the study . the drug‐treated group showed significantly better blood pressure control than the group not given antihypertensives .  Induction of labor before term , because of maternal or fetal complications , was somewhat more frequent in the control group . Nine women in the treatment group and 5 in the control group developed albuminuria . Three infants in the drug‐treated group died perinatally , and one in the control group . the outcome for the newborns was similar in both groups concerning birth weight , head circumference and Apgar score and in the frequencies of respiratory distress , bradycardia and hypoglycemia . the better blood pressure control achieved with these drugs makes it possible to treat the patient at home and reduce the risk of emergency delivery , but treatment does not seem to be m and atory for a good outcome of the pregnancy in cases of mild and moderate hypertension during pregnancy OBJECTIVE AND DESIGN The aim of this study was to evaluate treatment of mild to moderate hypertension ( less than 170/110 mmHg ) in pregnancy in a prospect i ve , r and omised , double-blind trial . SETTING AND PATIENTS Pregnancy outcome was studied for 52 primigravid women , managed in hospital from early in the third trimester . INTERVENTIONS Patients were r and omly allocated either to placebo or to active treatment ( clonidine plus hydralazine ) . MAIN OUTCOME MEASURES AND RESULTS Maternal deterioration dictated withdrawal from trial therapy for eight patients receiving placebo , but for only one receiving active treatment . Maternal proteinuria occurred only in the placebo group . Intention-to-treat analysis showed a significant increase in premature delivery for complications in the placebo group ( P less than 0.05 ) , despite active blood pressure treatment for those withdrawn from the group because of severe hypertension ( 170/110 mmHg or higher ) . Neonatal respiratory distress requiring intensive care occurred only in babies born to women in the placebo group . There were no perinatal deaths and no adverse effects of treatment in the neonates . CONCLUSIONS The study indicates that early control of mild hypertension in pregnancy can prevent progression to emergency premature delivery Objective . To evaluate l-arginine ( l-Arg ) supplementation in pregnant women with chronic hypertension and its effects on blood pressure ( BP ) and maternal and neonatal complications . Methods . We enrolled 80 women affected by mild chronic hypertension referred to the High Risk Clinic of the Mother – Infant Department of the University of Modena and Reggio Emilia . Each woman after obtaining oral consent was r and omized to receive oral l-Arg versus placebo and thereafter su bmi tted to 24-h ambulatory BP monitoring . The primary outcome was BP change after 10–12 weeks of treatment . Secondary outcomes were as follows : percentage of women on antihypertensive treatment at delivery , maternal , and fetal outcome . Results . The BP changes after 10–12 weeks of treatment did not differ between groups . A lower percentage of women received antihypertensive drugs in the l-Arg group than the placebo group . The incidence of superimposed preeclampsia indicated delivery before the 34th weeks and certain neonatal complications tended to be higher in the placebo group . Conclusions . l-Arg supplementation in pregnant women with mild chronic hypertension does not significantly affect overall BP but is associated with less need for antihypertensive medications and a trend toward fewer maternal and neonatal complications . The results of the study were limited by the small sample size and by the exclusion of women with severe chronic hypertension . In our policy , these patients needed many hypertensive drugs and were normally managed by the cardiologist . Nevertheless , considering the promising results on maternal and fetal outcome , we believe that further studies should be performed to confirm such data and to clarify the role of l-Arg as a protective supplement in high-risk pregnancy 195 ( 97.5 % ) children born to hypertensive women participating in a trial of methyldopa treatment during pregnancy were followed from birth and were extensively examined at the age of 7 1/2 years . The frequency of problems with health , physical or mental h and icap , sight , hearing , and behaviour was the same in children of treated and untreated women . Sons of the untreated women were heavier and taller than those of treated women , as were their mothers . Among children of women who entered the trial between 16 and 20 weeks ' gestation , sons of untreated women had larger heads than sons of treated women , but there was no difference in mean intelligence quotients . There were no significant differences between the children in the treated and untreated groups in st and ing and supine blood pressures , or fourteen tests of ability .  Methyldopa therefore seems safe to use in pregnancy and is probably preferable to other drugs from the point of view of the neonate and child Summary : Doppler studies of the uterine and umbilical arteries were performed in 24 acutely hypertensive pregnant women . Women were divided into 2 groups : Group 1 ( diastolic blood pressure (DBP)>110 mm Hg ) received placebo ( n = 6 ) or 10 mg oral nifedipine ( n = 9 ) ; Group 2 ( DBP ≥ 110 mm Hg ) received 10 mg oral nifedipine ( n = 5 ) or 10 mg intravenous hydralazine ( n = 4 ) . Treatment allocations were r and om within groups and the investigator and patient were blind to the treatments . Baseline flow velocity waveforms ( FVW ) and posttreatment FVW 's at 30 , 60 and 120 minutes were recorded . There was no significant difference between baseline and posttreatment FVW indices within or between groups . Placebo was as effective as nifedipine in lowering blood pressure over 2 hours of study . There were no significant adverse effects of treatment Three hundred women with mild chronic hypertension at 6 to 13 weeks ' gestation were r and omly allocated to receive either methyldopa or labetalol or be in the control group . Thirty-seven women ( 12 % ) were excluded for various reasons . Of the remaining 263 patients , 90 received no drug , 87 received methyldopa , and 86 received labetalol . All 263 were followed throughout pregnancy with serial renal function tests and serial assessment of fetal status . There were no differences among the three groups in mean systolic or diastolic blood pressures , mean gestational age , or initial laboratory findings at time of entry . Patients treated with medications had significantly lower ( p less than 0.0001 ) systolic and diastolic blood pressures throughout gestation compared with the no-medication group . Among the control group there was a spontaneously significant lowering ( p less than 0.0001 ) of both systolic and diastolic blood pressures at 14 to 26 weeks ' gestation . However , there were no differences among the three groups regarding the incidences of either superimposed preeclampsia ( 15.6 % , 18.4 % , and 16.3 % , respectively ) , abruptio placentae ( 2.2 % , 1.1 % , and 2.3 % , respectively ) , or preterm delivery ( 10 % , 12.5 % , and 11.6 % , respectively ) . In addition , there were no differences among the groups regarding gestational age at delivery , birth weight , incidence of fetal growth retardation , or neonatal head circumference . There was one midtrimester loss in the methyldopa group and one stillbirth in each of the other groups . We conclude that treatment of maternal blood pressure in mild chronic hypertension during pregnancy did not improve perinatal outcome 1 . This study evaluates the perinatal outcome of infants born to ninety‐five mothers with hypertension in pregnancy whose blood pressure was treated in a double blind trial comparing clonidine hydrochloride ( C ) and α‐methyldopa ( A ) OBJECTIVE To compare the antihypertensive effects of epoprostenol sodium ( prostacyclin ) with that of dihydralazine in acute hypertensive crises of pregnancy . DESIGN A prospect i ve r and omized study . A minimum of 20 patients per group was considered statistically acceptable ( alpha = 0.05 , power = 0.9 ) . SETTING A large urban tertiary hospital . SUBJECTS Forty-seven pregnant patients with diastolic blood pressures of > 100 mmHg were studied . INTERVENTION Lowering of high blood pressure with either dihydralazine ( n = 25 ) , the st and ard drug for this purpose , or epoprostenol ( n = 22 ) . MAIN OUTCOME MEASURE A significant drop in high blood pressure was regarded as a fall of 15 mmHg diastolic and 30 mmHg systolic blood pressure . RESULTS There were no statistically significant differences in the antihypertensive effects between the two treatment groups . Epoprostenol infusion caused less tachycardia ; the mean pulse rate changed from 81.77 beats/min , before treatment to 88.36 at stabilization , compared with a change from 80.96 beats/min to 102.68 in the group treated with dihydralazine ( P = 0.0024 ) . CONCLUSION The place of epoprostenol in pregnancy might be in patients with severe hypertension and tachycardia and in those requiring acute control of severe hypertension on the operating table before general anaesthesia BACKGROUND Hypertension is associated with increased maternal and fetal mortality and morbidity . While there is consensus that severe hypertension should be treated , antihypertensive treatment for mild chronic hypertension during pregnancy remains controversial . OBJECTIVE To evaluate clinical course , and maternal and perinatal outcomes of pregnant women with mild chronic hypertension without other disease , under strict control of maternal hypertension ( target dBP of 85 - 89 mmHg ) . PATIENTS AND METHODS We conducted a prospect i ve cohort study of 110 pregnant women with mild chronic hypertension without other disease ; clinical course was classified in three groups : stable condition , exacerbation of hypertension and superimposed preeclampsia . We compare maternal and perinatal outcomes ; statistical comparisons were performed by ANOVA test . Relative risk ( RR ) was calculated for adverse perinatal outcomes . RESULTS Atotal of 110 women were included , mean maternal age was 33 + /- 5.8 years . There were 78 ( 71 % ) women with stable condition , 26 ( 24 % ) with exacerbation of hypertension and 6 ( 5 % ) with superimposed preeclampsia ( PE ) . Women with superimposed PE and exacerbation of hypertension delivered earlier and had more small for gestational age ( SGA ) babies than women with stable condition and exacerbation . Delivery route was vaginal in 45 patients ( 40 % ) while 65 patients ( 60 % ) underwent cesarean section in order to avoid fetal distress . CONCLUSIONS Results demonstrated that fetuses in the stable condition group ( strict control ) did not have worst outcomes than those in the other groups . This cohort study shows efficacy and safety of treating mild chronic hypertension during pregnancy Summary . Two treatment strategies were compared in 155 women with pregnancy‐induced hypertension who were also given comprehensive non‐pharmacological care . The mean gestation at entry was 28 weeks . As long as the diastolic blood pressure ( DBP ) remained below 106 mmHg , oxprenolol , or oxprenolol plus dihydralazine , were given to the early treatment group , and matching placebos to the control group . Open antihypertensive treatment was provided for patients whose DBP rose above 105 mmHg . Proteinuria occurred in seven women in each group . In the early treatment group , 13 of the 78 women were delivered by caesarean section ; the corresponding numbers in the control group were 27 of 76 ( 17 vs 36 % , 95 % confidence interval ( CI ) of difference : 5‐33 % ) ; the sections included seven and 16 in the early treatment and control groups , respectively , for severe hypertension and /or fetal distress . There were five perinatal deaths , two in the early treatment group and three in the control group . Early treatment did not influence gestational age at birth or birthweight . Respiratory distress syndrome occurred in four infants in the early treated group and in 10 in the control group ; 14 infants in the former group and 26 in the latter were in hospital for more than 10 days ( 18 vs 35 % ; 95 % CI of difference 4.32 % ) . These results indicate that early antihypertensive treatment with oxprenolol  is safe for the fetus and newborn in pregnancy‐induced hypertension , but has no advantage over non‐pharmacological care in terms of fetal growth . However , it may prevent acute hypertension in late pregnancy and associated fetal distress , and thus reduce the number of caesarean sections 242 women completed a controlled trial of methyldopa ( ' Aldomet ' ) for moderate hypertension in pregnancy . Active treatment was associated with a significantly improved fetal outcome , due in part to a reduced number of mid-pregnancy abortions . There were 9 pregnancy losses in the control group , which included 4 mid-pregnancy abortions , and 1 fetal loss in the treated group . The birthweight and maturity of viable infants were similar in treated and control groups , and a detailed multivariate analysis confirmed that hypotensive treatment had no effect on fetal growth in utero . The better outcome associated with treatment was not due to the prevention of pre-eclampsia , and may be partly due to a direct or indirect effect of methyldopa on uterine activity . Methyldopa is safe to use for the treatment of hypertension in pregnancy in the context of close medical and obstetric supervision A controlled prospect i ve evaluation of pregnancy complicated by chronic hypertension is proposed and preliminary data on population selection and pregnancy outcome are presented . Sixty-three women with evidence of underlying hypertensive disease were followed prospect ively throughout pregnancy . Twenty-three patients were followed in a protocol of intensified prenatal care and r and omized assignment of antihypertensive agents : placebo , hydralazine , or methyldopa .  Forty patients were followed in the high-risk pregnancy clinics at Duke University . The incidence of preeclampsia in the r and omized prophylactic antihypertensive group was statistically lower than that in the nonr and omized group ( 8.7 versus 32.5 % ; P<.01 ) . There were no other statistically significant differences between the groups . The 63 hypertensive women had a high incidence of diabetes mellitus diagnosed during pregnancy ( 49.2 % ) as compared to the authors ' general obstetric population ( 8.1 % ) OBJECTIVE To compare nifedipine ( group 1 ) with methyldopa ( group 2 ) in the management of pregnancy induced hypertension ( PIH ) . DESIGN A prospect i ve clinical trial . SETTING Obstetric Unit , General Hospital , Peradeniya . PATIENTS A total of 126 patients with PIH were allocated alternately to either group . The patients in group 1 received nifedipine 30 to 90 mg/day and in group 2 methyldopa 750 to 2000 mg/day . MEASUREMENTS Blood pressure , the extra days added to the pregnancy , number of patients treated for acute hypertensive episodes , maturity of fetus at birth , mode of delivery , birth weight , intrauterine deaths , Apgar score , maternal side effects and complications . RESULTS The two groups on admission to the study had similar periods of gestation ( group 1 , 33.6 + 5.9 , group 2 , 34.1 + 4.2 ) , systolic blood pressure in mmHg ( 151 + 22 , and 154 + 24 ) and diastolic blood pressure ( 108 + 12 , and 108 + 12 ) . The results showed no differences between the two groups , with respect to maturity of fetus at delivery ( 35.1 + 5.5 , and 35.7 + 2.9 ) , mode of delivery , number of intrauterine deaths , average systolic blood pressure in mmHg ( 148 + 14 and 152 + 16 ) , average diastolic blood pressure ( 102 + 8 and 104 + 9 ) , highest systolic blood pressure ( 169 + 24 and 167 + 30 ) , highest diastolic blood pressure ( 115 + 12 and 116 + 11 ) , birth weight in kg ( 2.015 + 0.957 , and 1.922 + 0.660 ) and number of days added to the pregnancy ( 7 + 7 , 9 + 11 ) . The Apgar score for group 2 was better than in group 1 , and less patients in group 2 required treatment for acute hypertension during the period of study . CONCLUSIONS The results of our study indicate that nifedipine is as effective as methyldopa in the treatment of PIH A total of 242 women with moderate hypertension in pregnancy completed a controlled trial of methyldopa ( Aldomet ) . The hypotensive effect of methyldopa was similar to its action in non‐pregnant individuals and greatly reduced the frequency of severe hypertension occurring antenatally and in labour . As pregnancy advanced , an increasing daily dose of methyldopa was needed and there was a greater use of additional hypotensive therapy . Seventeen ( 14·5 per cent ) women assigned to methyldopa had to be transferred to another drug or had to stop treatment completely because of minor side effects , of which the commonest were lack of energy and dizziness . No serious side effects were encountered . Nine per cent of the untreated women developed severe hypertension which required treatment later in their pregnancies . Six weeks after delivery , nearly all the patients were able to stop OBJECTIVE To prospect ively determine whether moderate exercise during pregnancy lowers blood pressure . STUDY DESIGN A r and omized , controlled trial with one test group and one control group . All subjects have a history of mild hypertension , gestational hypertensive disorders or a family history of hypertensive disorders . Subjects were recruited before 14 weeks ' gestation . After four weeks of observation , the subjects were r and omly assigned to either the exercise or control group . The exercise group visited the laboratory three times a week for 10 weeks ( 18 - 28 gestation weeks ) to perform 30 minutes of exercise at Rating of Perceived Exertion level 13 . RESULTS A total of 16 pregnant women ( mean age , 30 years ) participated . The mean metabolic equivalent during exercise sessions was 4.7 ( SD = 0.8 ) . Blood pressure measurements were compared before and after the 10-week exercise period in the two groups . Systolic blood pressures did not change significantly , but diastolic blood pressure ( DBP ) in the exercise group decreased by 3.5 mm Hg , while that in the control group increased by 1.1 mm Hg . Thus , the pre-post change in DBP differed by 4.6 mm Hg between groups . Exercise treatment reduced the diastolic blood pressure to a near-significant level in the exercise group ( t = 2.34 , df = 7 , P = .052 ) . Percent body fat did not differ between the exercise and control groups either before or after exercise treatment . ANOVA revealed that pregnancy had a significant effect ( F(1 , 14 ) = 5.7 , P = .03 ) on increasing the percentage of fat , but exercise treatment did not ( F(1 , 14 ) = .18 , P = .68 ) . Estimated energy expenditure in overall daily physical activities during the intervention did not differ between the two groups despite the inclusion of exercise . CONCLUSION This study detected a strong trend that 10 weeks of moderate exercise lowered the  diastolic blood pressure among pregnant women at risk of hypertensive disorders . The reductions were probably due to the effect of exercise itself , not to weight or overall daily physical activity levels Abstract Objectives . To assess the efficacy and safety of nicardipine in comparison to labetalol in the initial management of severe hypertension in pregnancy . Design . R and omized prospect i ve study . Setting . The obstetric ward of the teaching hospital of Monastir Tunisia . Patients . Sixty consecutive pregnant women admitted beyond the 24th week of pregnancy with severe hypertension . Intervention . Patients were r and omly assigned to receive intravenously for 1 h either labetalol ( n=30 ) or nicardipine ( n=30 ) . Treatment was titrated to achieve a 20 % lowering of blood pressure ( BP ) . Measurements . Maternal BP and heart rate were measured at inclusion and repeatedly during the first hour following the drugs administration . Fetal heart rate was recorded throughout the study period . The main outcome endpoints were the success rate and the length of time needed to achieve the therapeutic goal . The rate of maternal and fetal adverse events and dose adjustments were also analyzed . Results . Labetalol and nicardipine achieved the 20 % lowering in BP in the same proportion ( 63 % and 70 % success rates , respectively ) . Overall nicardipine caused a significantly greater decrease in systolic and diastolic BP . No patient had any episode of hypotension . The length of time to achieve the BP goal was also similar ( 12 vs. 11 min , respectively ) . Both drugs were well tolerated except for a moderate tachycardia observed with the use of nicardipine . Conclusion . Nicardipine and labetalol are effective and safe in the initial treatment of severe hypertension of pregnancy Hypertensive disorders of pregnancy are associated with vascular dysfunction in the pregnancy and an increased risk of long-term cardiovascular disease ( CVD ) in the mother . What remains to be understood is whether the length , severity of the disease , the treatment of hypertension in pregnancy , or the subtype of hypertensive disorders of pregnancy are significant predictors of future CVD . We undertook a retrospective cohort study to review all women who gave birth at a tertiary hospital in Sydney between the years 1980 and 1989 ( n=31 656 ) . A cohort of women was further defined by having hypertension during the antenatal , intrapartum , or postnatal periods ( n=4387 ) . R and omly selected records of women ( n=1158 ) with a hypertensive disorder of pregnancy were individually review ed to collect data on their pregnancy and pregnancy outcomes . The entire cohort then underwent linkage analysis to future CVDs . Women who presented with gestational hypertension were at greater risk of future hypertension and ischemic heart disease compared with the women who were diagnosed with preeclampsia . There was no significant difference between the women who were treated with antihypertensive medication and the women who did not receive antihypertensive medication or the duration of hypertensive disorders of pregnancy and future admission for CVD , although severity of hypertension tracked with increased risk of future hypertension in all groups . This study demonstrated that all women who present with any of the subtypes of hypertensive disorders in pregnancy are at significant risk of future CVD compared with women who remain normotensive during their pregnancy
Hydralazine was the most common drug for others to be evaluated against .
Diazoxide , given as 75 mg bolus injections , appears to be associated with maternal hypotension requiring treatment , and ketanserin is less effective than hydralazine at reducing blood pressure .
There is no other clear evidence that any one of the other antihypertensive agents is better than another for women with severe hypertension during pregnancy .
Exceptions are diazoxide and ketanserin , which are probably not good choices
BACKGROUND Very high blood pressure during pregnancy poses a serious threat to women and their babies .
The use of drugs to lower blood pressure will reduce this risk for the women , and possibly also for the baby .
OBJECTIVES The objective of this review was to compare different antihypertensive drugs used for treatment of severe hypertension during pregnancy .