title: Randomised controlled trial of atenolol and pindolol in human pregnancy: effects on fetal haemodynamics. Antihypertensive treatment in pregnancy: analysis of different responses to oxprenolol and methyldopa. Glycemia in newborns of hypertensive mothers according to maternal treatment. Atenolol in essential hypertension during pregnancy. Preeclampsia: haemostatic status and the short-term effects of methyldopa and isradipine therapy. Labetalol vs. methyldopa in the treatment of pregnancy-induced hypertension. Maternal and fetal haemodynamics in hypertensive pregnancies during maternal treatment with intravenous hydralazine or labetalol PLACEBO-CONTROLLED TRIAL OF ATENOLOL IN TREATMENT OF PREGNANCY-ASSOCIATED HYPERTENSION Comparison of outcome of labetalol or hydralazine therapy during hypertension in pregnancy in very low birth weight infants Beta-adrenergic blocking agents in the treatment of pregnancy-induced hypertension. A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy. Obstetric aspects of the use in pregnancy-associated hypertension of the beta-adrenoceptor antagonist atenolol. Propranolol in pregnancy three year prospective study. The Effect of Prophylactic Management and Therapeutics on Hypertensive Disease in Pregnancy: Preliminary Studies Flow velocity analysis of umbilical and uterine artery flow in pre-eclampsia treated with propranolol or pindolol. Atenolol and fetal growth in pregnancies complicated by hypertension. A comparison of labetalol plus hospitalization versus hospitalization alone in the management of preeclampsia remote from term. A PROSPECTIVE CONTROLLED TRIAL OF METOPROLOL‐HYDRALAZINE TREATMENT IN HYPERTENSION DURING PREGNANCY Treatment of hypertension during pregnancy with hydralazine monotherapy or with combined therapy with hydralazine and pindolol. A randomized comparison of early with conservative use of antihypertensive drugs in the management of pregnancy‐induced hypertension Comparison of the alpha and beta blocking drug, labetalol, and methyl dopa in the treatment of moderate and severe pregnancy-induced hypertension. Does labetalol influence the development of proteinuria in pregnancy hypertension? A randomised controlled study. Nicardipine Versus Metoprolol in the Treatment of Hypertension During Pregnancy: A Randomized Comparative Trial A comparative evaluation of metoprolol and methyldopa in the management of pregnancy induced hypertension. Randomised controlled comparative study of methyldopa and oxprenolol in treatment of hypertension in pregnancy. Neonatal Effects of Beta‐Blocking Drugs in Pregnancy [Maternal effects and perinatal safety of labetalol in the treatment of hypertension in pregnancy. Comparison with methyldopa in a randomized cooperative trial]. Intrauterine exposure to the beta-adrenergic receptor-blocking agent metoprolol and allergy. A randomised placebo controlled trial of labetalol in the treatment of mild to moderate pregnancy induced hypertension First year of life after the use of atenolol in pregnancy associated hypertension. Uterine and fetal hemodynamics and fetal cardiac function after atenolol and pindolol infusion. A randomized study. Prevention of preeclampsia: a randomized trial of atenolol in hyperdynamic patients before onset of hypertension. Magnesium sulphate for pre‐eclampsia and eclampsia: the evidence so far Management of pregnancy-induced hypertension with pindolol--comparative study with methyldopa. Randomised comparison of methyldopa and oxprenolol for treatment of hypertension in pregnancy.
abstract: OBJECTIVE --To compare the effects of uteroplacental circulation of two beta adrenoceptor blockers , atenolol ( cardioselective ) and pindolol ( non-selective with intrinsic sympathomimetic activity ) . DESIGN --Controlled double blind double dummy study . SETTING --Departments of obstetrics and gynaecology in two Swedish university hospitals . SUBJECTS--29 women with pregnancy induced hypertension in the third trimester , 13 r and omised to atenolol and 16 to pindolol .  MAIN OUTCOME MEASURES --Pulsatility index in fetal aorta , umbilical artery , and maternal arcuate artery . Volumetric blood flow in fetal aorta and umbilical vein . RESULTS --Mean arterial blood pressure decreased by 9.0 ( 95 % confidence interval -13.0 to -5.0 ) mm Hg in the atenolol group and by 7.8 ( -11.4 to -4.2 ) mm Hg in the pindolol group . During atenolol treatment the pulsatility index increased significantly from 1.82 ( SD 0.20 ) to 2.07 ( 0.32 ) in the fetal thoracic descending aorta , from 1.44 ( 0.28 ) to 1.79 ( 0.27 ) in the abdominal aorta , and from 0.93 ( 0.17 ) to 1.05 ( 0.19 ) in the umbilical artery ; the volumetric blood flow in the umbilical vein decreased from 106 ( 28.8 ) to 84 ( 22.6 ) ml/min/kg . No such changes were seen after treatment with pindolol . Birth weight was similar in the two groups but placental weight was significantly different ( 529 ( 122 ) g in atenolol group v 653 ( 136 ) g in pindolol group ; p = 0.03 ) . CONCLUSION --The hypotensive effect was similar with both drugs , but only the beta 1 blocker atenolol had significant effects on fetal haemodynamics , although within normal ranges . The implication s of these findings can be only speculative , but negative fetal consequences of beta 1 adrenoceptor blockade can not be excluded One hundred and eighty three hypertensive pregnant women were r and omly assigned to antihypertensive treatment with oxprenolol ( 96 women ) or methyldopa ( 87 women ) . Control of hypertension was equivalent in both treatment groups , and in 64 ( 35 % ) cases hydralazine had to be added to the treatment to achieve the therapeutic goal ( diastolic blood pressure below 85 mm Hg ) . Five perinatal deaths occurred , one in the oxprenolol group and four in the methyldopa group . Detailed analysis confirmed a previous report of greater fetal growth in the group treated with oxprenolol ; this trend was present regardless of severity of hypertension and parity . With increasing duration of treatment the differences between the two groups diminished , and there was no difference after 10 weeks of treatment , a finding that may explain some of the reported discrepancies among therapeutic studies . As hypertension in pregnancy may pursue an accelerated course , necessitating urgent delivery , and there is no satisfactory method of predicting the duration of treatment in individual patients fetal benefit is most likely to be achieved by treatment with oxprenolol , provided that there is no maternal contraindication to treatment with beta blockers PURPOSE To evaluate the evolution of glycemic levels in newborns of hypertensive mothers according to maternal treatment . METHODS Prospect i ve r and omized study , including 93 newborns of mothers treated with isradipine ( n = 39 ) , atenolol ( n = 40 ) , or low sodium diet ( control group - n=14 ) . Glycemia was determined at birth ( mother and newborn by the oxidase glucose method ) and in the 1st , 3rd , 6th , 12th , and 24th hours after birth ( newborn by a test strip method ) . The evolution of glycemia was analyzed in each group ( Friedman test ) . The groups were compared regarding glycemia ( Kruskall-Wallis test ) , and linear regression models were constructed for the analyses ( independent variable = maternal glycemia ; dependent variables = umbilical cord , 3rd , and 6th hour glycemia ) . RESULTS There were no statistically significant differences among the mean blood glucose levels of the 3 groups in any of the assessment s. There was a correlation between maternal and umbilical cord blood glucose in the isradipine ( r = 0.61 ; P < .05 ) and control ( r = 0.84 ; P < .05 ) groups . Regarding glycemia levels of the mothers and newborns in the third and sixth hours postpartum , this correlation was present only in the control group ( maternal x third hour : r = 0.65 ; P < .05 ; maternal x sixth hour : r = 0.68 ; P < .05 ) . There were no correlations in the atenolol group . Hypoglycemia was detected in 51.3 % of the isradipine group , 60 % of the atenolol group , and 35.7 % of the control group , and it was more frequent in the first hour postpartum in all groups . CONCLUSIONS The results suggest a similar effect of the 3 types of treatment upon newborn glycemia . The correlation analysis suggests that isradipine could have effects upon newborn glycemia only after birth ( correlation only in umbilical cord blood ) , whereas atenolol could act earlier ( there was no correlation at any moment ) . The results also point to the need for glycemic control from the first hour postpartum of newborns of hypertensive mothers whether they have or have not undergone treatment with antihypertensive drugs OBJECTIVE --To determine the effect of atenolol on the outcome of pregnancy in women with essential hypertension . DESIGN -- Prospect i ve , r and omised , double blind , placebo controlled study . SETTING --Hospital clinic . PATIENTS --33 Women with mild essential hypertension ( systolic blood pressure 140 - 170 mm Hg or diastolic pressure 90 - 110 mm Hg on two occasions at least 24 hours apart ) consecutively referred to two obstetric medical clinics . Four patients in the  placebo group were withdrawn from the study : control of blood pressure was inadequate in two , one developed breathlessness , and one changed her mind about participating . The mean gestation in the 29 remaining women on entry to the study was 15.9 weeks . MAIN OUTCOME MEASURES --Blood pressure and birth weight . INTERVENTION--14 Women received placebo . 15 Women received atenolol 50 mg daily initially , increasing until either the blood pressure was less than 140/90 mm Hg or a dose of 200 micrograms daily was reached . RESULTS --The mean blood pressure on entry was 148/86 mm Hg in the group given atenolol and 144/86 mm Hg in the group given placebo . During treatment the mean diastolic pressure was significantly reduced by atenolol compared with placebo ( to 74 v 81 mm Hg ; difference in means ( 95 % confidence interval ) 7.0 ( 2.9 to 10.0 ) mm Hg ) but the effect on systolic pressure was marginal ( 132 v 136 mm Hg ; 4.0 ( -1.4 to 8.6 ) mm Hg ) . Babies in the atenolol group had a significantly lower birth weight than those in the placebo group ( 2620 g v 3530 g ; 910 ( 440 to 1380)g ) . CONCLUSION --Atenolol given from the end of the first trimester in patients with mild hypertension is associated with intrauterine growth retardation . When taken in conjunction with the results of a previous study in which methyldopa was given these findings indicate that benefit is unlikely to result from treating mild essential hypertension in pregnancy OBJECTIVE To determine the haemostatic status in preeclampsia and to investigate the effects of short-term use of anti-hypertensive drugs , methyldopa and isradipine . METHODS Thirty preeclamptic ( PE ) women admitted to the hospital for observation and treatment were r and omized to receive either methyldopa or isradipine for 2 weeks . Their blood pressure were monitored for 24 h before treatment and again at 7 days and 14 days after treatment using the programmable automated ambulatory blood pressure ( ABP ) monitoring system . Blood sampling was performed before commencement of anti-hypertensive treatment , 7 days and 14 days after treatment and the haemostatic parameters studied was compared before treatment with normal pregnancy and the effect of anti-hypertensive treatment . Nineteen normal pregnant subjects with a total of 30 blood sampling at various gestation and good pregnancy outcome served as controls . The following haemostatic parameters were determined ; thrombelastography , fibrinogen , antithrombin III ( ATIII ) , thrombin-antithrombin (TAT)-complex , beta-thromboglobulin ( beta-TG ) , plasminogen activators ( t-PA , u-PA ) , plasminogen activator inhibitors ( PAI-1 , PAI-2 ) , and plasminogen . RESULTS Significant lowering of blood pressure was evident at Days 7 and 14 of therapy with either methyldopa or isradipine . Increased mean plasma fibrinogen and decreased ATIII levels were seen in preeclampsia together with decreased u-PA and t-PA activity levels in contrast to increased t-PA antigen and beta-TG . No significant differences were seen for TAT-complex , PAI-1 , plasminogen and D-dimer levels although their mean levels were higher than observed in non-pregnant subject except for PAI-2 , the level was significantly reduced when compared with normal pregnancy . Two-way analysis of variance showed no significant alteration on all haemostatic parameters studied in preeclamptic women receiving either methyldopa or isradipine after 7 and 14 days of therapy . CONCLUSION Enhance activation of coagulation was observed together with raised fibrinolysis in normal pregnancy and PE . However , in PE a further reduction in ATIII , u-PA and PAI-2 with increased fibrinogen and platelet activation could lead to an imbalance in the coagulation/fibrinolysis equilibrium which favours fibrin deposition . All these changes seen in PE including the coagulation kinetics were not altered by the short term effects of methyldopa and isradipine even though significantly lowered blood pressure were observed during therapy OBJECTIVE To assess the efficacy and safety of labetalol compared with methyldopa in the management of mild and moderate cases of pregnancy-induced hypertension ( PIH ) . METHODS One hundred four primigravidas with PIH were r and omly allocated to receive either labetalol ( group A ) or methyldopa ( group B ) . The dose of the drugs was doubled every 48 h to maintain a mean arterial blood pressure < or = 103.6 mmHg . Clinico-biochemical effects and frequency of side effects were studied . The statistical level of significance was taken at P < 0.05 . RESULTS Ten patients in group B ( 18.5 % ) developed significant proteinuria ( > 30 mg/dl ) whereas none developed proteinuria in group A. Labetalol was quicker and more efficient at controlling blood pressure , having a beneficial effect on renal functions and causing fewer side effects compared with methyldopa . The rate of induction of labor and rate of cesarean section for uncontrolled PIH was less in group A ( 48 % and 1 % , respectively ) compared with group B ( 63.0 % and 5.6 % , respectively ) . Moreover a higher Bishop score at induction of labor was noticed in group A. CONCLUSIONS Labetalol is better tolerated than methyldopa , gives more efficient control of blood pressure and may have a ripening effect on the uterine cervix Summary . Intravenous treatment with 10 mg of hydralazine or 100 mg of labetalol was r and omly allocated to 30 hypertensive pregnant women .  Umbilical artery flow velocity waveforms were recorded using a pulsed Doppler duplex scanner ( ATL Mk V ) and umbilical artery pulsatility index ( PI ) and fetal heart rate ( FHR ) were derived from these recordings . Maternal blood pressure decreased significantly after both drugs . Maternal pulse rate increased after hydralazine but did not change significantly after labetalol . FHR did not change significantly after hydralazine but decreased after labetalol . PI decreased after hydralazine and increased after labetalol‐most fetuses showed little change but a few in each group showed large changes in PI , as did two of five additional patients studied . We attributed the decrease in PI in some fetuses after hydralazine to vasodilation , and the increase in PI in some fetuses after labetalol to vasoconstriction in the fetoplacental circulation , suggesting that fetal beta‐blockade may occur after maternal treatment with labetalol Atenolol was compared with placebo in a r and omised and double-blind prospect i ve study of 120 women with mild to moderate pregnancy-associated hypertension who were also initially managed conventionally by bed rest .  Atenolol given once daily significantly reduced blood-pressure , prevented proteinuria , and reduced the number of hospital admissions . Loss of blood-pressure control leading to withdrawal from the study was commoner among the placebo group , whose babies had a high morbidity . Respiratory distress syndrome occurred only in the placebo group . Intrauterine growth retardation , neonatal hypoglycaemia , and hyperbilirubinaemia occurred with the same frequency in the two groups . Neonatal bradycardia was more common after atenolol but the systolic blood-pressure of the babies was the same in both groups . There was no difference between the groups in maternal symptoms which could have been attributed to beta-blocker therapy . Thus atenolol is more effective than conventional obstetric management in this form of hypertension and does not adversely affect mother or baby Ninety‐seven women with moderate to severe preeclampsia ( PE ) were allocated at r and om to labetalol or hydralazine treatment . Of these , 22 women with severe PE gave birth to neonates with VLBW ( very low birth weight ≥ 1500 g ) . Seven were allocated to labetalol treatment ( Group A ) , eight to hydralazine treatment ( Group B ) and seven women received both drugs due to poor blood pressure control with a single drug therapy ( Group C ) . No difference in cesarean section rate or in the indication for operative delivery could be seen . Gestational age was 29.9 weeks ( 25.4–32.5 ) in Group A. 28.6 weeks ( 26.6–33.4 ) in Group B and 27.3 weeks ( 26.7–31.1 ) in Group C  (  median and range ) . Birth weight did not differ between groups and 13 of the 22 infants weighed below 1000 g. There was a tendency to lower Apgar scores at five minutes in the hydralazine group . Time spent in the neonatal intensive care unit did not differ between groups . Five of the 11 neonates with gestational age (GA)≥28 weeks and three of the seven neonates in GA 29–30 weeks died . Neither the number of infants requiring intermittent positive pressure ventilation or duration of O2‐treatment , nor number of infants with respiratory distress syndrome differed between groups . We did not find any difference in the outcome of the VLBW infants when the hypertensive mother had been treated with either hydralazine or labetalol Fifty-one women with pregnancy-induced hypertension ( PIH ) were r and omly allocated to one of three treatment groups : A : hydralazine ( 13 ) ; B : hydralazine and propranolol ( 17 ) ; and C : hydralazine and pindolol ( 19 ) . All women fulfilled the pretreatment criteria and were of similar age , numbers of previous pregnancies and had systolic blood pressure ( SBP ) of between 140 and 160 mmHg and diastolic blood pressure ( DBP ) of between 95 and 110 mmHg .  Hypertension was treated equally well by all three regimens ( mean SBP was 133.6 , 130 and 134 mmHg , respectively ) . Heart rate was significantly higher than baseline in group A and lower in groups B and C , as is to be expected with beta-blocker treatment . Side-effects were more frequent in group A than in groups B and C , 62 % of the patients on hydralazine monotherapy complained of palpitations compared to 35 % on combination treatment . Fetal outcome differed in the various groups . Birth weight was significantly lower in group B , where regimen included propranolol , compared to that of group C , for whom the regimen included pindolol ( 3,044.7 + /- 443.8 and 2,709.6 + /- 485.5 gm , p < 0.05 ) . Mean blood glucose of the newborns were similar in groups A and C ( 76.5 + /- 16.5 and 78.6 + /- 15 gm% ) and significantly lower in group B ( 62.6 + /- 14 gm% , p < 0.02 ) . In conclusion , blood pressure was equally well treated in all three treatment groups . However , more maternal side-effects occurred in group A , the group treated with hydralazine monotherapy , while propranolol in combination with hydrazaline ( group B ) had some negative effects on fetal development which did not occur in pindolol/hydrazaline combination 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 The obstetric implication s of the use of the beta-adrenoceptor antagonist atenolol have been evaluated in a prospect i ve , r and omized , double-blind , and placebo-controlled study involving 120 women with pregnancy-associated hypertension . The clinical interpretation of antenatal and intrapartum cardiotocographs was uninfluenced by atenolol .  Human placental lactogen concentration fell in the atenolol group , but this was not an indicator of subsequent fetal distress . Other obstetric indices , such as urinary estriol excretion , were the same in both groups . Spontaneous premature labor occurred in five women receiving placebo but in none who received atenolol . Together with previously reported findings on pregnancy outcome , our study leads us to conclude that beta-blockers such as atenolol can appropriately be used in the management of hypertension during pregnancy We compared propranolol with methyldopa in a r and omized prospect i ve study of 28 women with pregnancy associated hypertension . Both drugs were equally effective in controlling maternal hypertension . There was no significant difference in the birthweights of the babies in each group . However one infant born to a mother receiving propranolol had symptomatic hypoglycaemia . The mean peak levels of propranolol , propranolol glucuronide , 4-hydroxypropranolol , and 4-hydroxypropranolol glucuronide were not significantly different in the first , second , third trimesters and at least 3 months post partum . The mean peak plasma level of naphthoxylactic acid however was significantly less in the third trimester compared with post partum levels . Propranolol and its metabolites were found to cross into breast milk with the maximum dose likely to be ingested by the infant as either propranolol or propranolol glucuronide being 7 micrograms of propranolol per 100 g of breast milk , being approximately 0.1 % of the maternal dose 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 % ) In a double blind study , 20 gravidas with pre-eclampsia were r and omly allocated to treatment with either propranolol 120 mg/day or pindolol 15 mg/day for 7 days . Flow velocimetry was performed before and after treatment to assess the influence of these two regimens of beta blocker on the feto-placental circulation . A continuous wave Doppler unit was used to measure umbilical and uterine artery flow velocity waveforms . The systolic/diastolic ( A/B ) ratio and the systolic minus diastolic divided by systolic (A-B)/A ratio ( resistance index ) were used as indexes of blood flow resistance in the umbilical and uterine arteries , respectively . A resistance to flow in the uteroplacental circulation was significantly less in patients treated with pindolol compared to those treated with propranolol ( P less than 0.01 ) . The same pattern was also found in umbilical velocimetry , although the statistical significance was borderline ( P = 0.06 ) . Although both drugs were equally effective in reducing blood pressure at rest , their effect on the peripheral resistance was different . Pindolol appears to act in part through a peripheral vascular mechanism . Our data support this assumption because the flow in the uteroplacental bed , as reflected by a decrease in resistance index , improved when patients were treated with the drug pindolol Atenolol use may be associated with growth retardation when given in pregnancy , although the relationship to trimester of initiation , duration of treatment , and its use as monotherapy is still uncertain . To compare the obstetric and fetal outcome between women receiving atenolol ( as monotherapy ) and other antihypertensive drug monotherapies , and also to investigate the effect of duration of treatment on fetal growth , we performed a retrospective cohort study of 312 pregnancies in 223 women attending an Antenatal Hypertension Clinic .  Atenolol ( as monotherapy ) was given in 78 pregnancies ( 25.0 % ) , other types of antihypertensive drugs as monotherapy were given in 53 pregnancies ( 17.0 % ) , and multiple drug combinations were given in 90 pregnancies ( 28.8 % ) . In 91 pregnancies ( 29.2 % ) no antihypertensive drugs were given . Atenolol was found to be associated with lower birth weight and ponderal index values , with a trend toward a higher prevalence of preterm ( < 37 weeks ) delivery and small-for-gestational-age babies when compared to other antihypertensive drugs as monotherapy , or to no treatment . The adverse effect of atenolol  was more pronounced in women receiving the drug earlier in their pregnancy , and continuing the drug for a longer duration . In conclusion , atenolol should be avoided in the early stages of pregnancy and given with caution at the later stages , as it is associated with fetal growth retardation , which is related to duration of treatment Two hundred primigravid women with mild preeclampsia at 26 - 35 weeks ' gestation were r and omly allocated to treatment with hospitalization alone or combined with labetalol . There were no differences between the two groups in mean systolic or diastolic pressures , mean gestational age , or initial laboratory findings at time of entry . Patients in the labetalol group demonstrated a statistically significant ( P less than .005 ) decrease in blood pressure during treatment . No such decrease occurred in the hospitalization-alone group . Both groups exhibited significant deterioration in proteinuria , creatinine , and uric acid . The average days of pregnancy prolongation ( mean + /- SD ) were 21.3 + /- 13 and 20.1 + /- 14 days in the hospitalization and labetalol groups , respectively . There were no differences between the groups regarding any of the following : gestational age at delivery , birth weight , number of infants admitted to the special care unit , or cord blood gas measurements . However , the incidence of small-for-gestational-age infants was significantly higher in the labetalol group ( 19 versus 9 % , P less than .05 ) . There were no stillbirths , but one neonatal death in the labetalol group . Treatment of maternal blood pressure in preeclamptic pregnancies with labetalol  did not improve perinatal outcome , and was associated with a higher frequency of fetal growth retardation 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 Forty-four consecutive patients referred for treatment because of hypertension ( greater than 150/90 mmHg ) occurring during pregnancy were r and omly allocated to one of two treatment groups , hydralazine alone ( n = 21 ) or hydralazine combined with pindolol ( n = 23 ) . Satisfactory blood pressure control ( diastolic pressure less than 90 mmHg ) was achieved in 86 % of patients receiving hydralazine alone and 91 % of those on combined therapy . Although the treatment did not lower the overall incidence of hypertensive complications it appeared to delay the onset of such complications until successful surgical intervention was possible . Fetal outcome was similar in both groups and there was no perinatal mortality in this high-risk population . Although blood pressure control was similar in both groups of patients , combined therapy with hydralazine and pindolol can be considered to be superior to hydralazine monotherapy , since in patients treated with the combination the incidence and intensity of troublesome side-effects was markedly lower 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 Twentysix women with pregnancy-induced hypertension have been r and omly treated with either labetalol or Aldomet . A more satisfactory control of blood pressure was obtained with labetalol with minimal side-effects . After two weeks of treatment with labetalol  renal function had significantly improved with a markedly lower incidence of proteinuria . More patients went into spontaneous labour following labetalol than following Aldomet ; the Bishop score was also higher in this group . No adverse effects attributable to labetalol were noted in the baby either ante- or post-natally It is the development of proteinuria in pregnancy-induced hypertension which is associated with an increased perinatal mortality . There is some evidence to suggest that labetalol may diminish the amount of proteinuria in patients who have already developed proteinuric pre-eclampsia . A r and omised controlled study design was used to investigate whether labetalol treatment , started when a persistent diastolic blood pressure greater than 90 mmHg was observed , influenced the subsequent development of proteinuria . One hundred and fourteen women with singleton pregnancies and hypertension in the absence of proteinuria were r and omised to receive either labetalol or no antihypertensive therapy .  At recruitment maternal age , blood pressure and gestation  were similar in both the labetalol and control groups . There was no difference in the frequency , quantity or timing of subsequent proteinuria between treatment and control groups . Overall 34 % of primigravidae and 10 % of parous women developed proteinuria .  Labetalol did , however , control the blood pressure in 45 of the 51 treated women ( 88 % ) within 24 h. This effect was often shortlived requiring dose escalation after 3 to 5 days in the majority of cases . Labetalol was well tolerated and no significant maternal toxicity was noted Objective To compare the effects of treatment with nicardipine and metoprolol in patients with hypertension during pregnancy Thirty patients matched for age , parity , socioeconomic status and severity of pregnancy induced hypertension ( PIH ) were r and omly allocated to treatment with metoprolol or methyldopa . The average fall in diastolic blood pressure was significant in the group treated with metoprolol as compared with the methyldopa group ( p less than 0.01 ) . There were 3 perinatal deaths in the methyldopa group and 1 in the metoprolol group ; the mean birth weight of the babies was higher in cases treated with metoprolol . The results suggest metoprolol to be more efficacious with regard to control of hypertension and fetal outcome in cases of pregnancy induced hypertension One hundred pregnant women with hypertension ( defined as diastolic blood pressure at or above 95 mm Hg ) were allocated at r and om to treatment with methyldopa or oxprenolol and were compared with nonhypertensive controls matched according to parity and gestation at delivery . The patients were also stratified into those entering the study early ( before 32 weeks ' gestation ) and those entering late ( after 32 weeks ' gestation ) . Although there were no differences in diastolic blood pressure between the hypertensive groups before or during treatment , in the early entry group the systolic blood pressure at entry of those allocated to oxprenolol was significantly higher than that of those receiving methyldopa ; this difference remained throughout the treatment period . Also in the early entry group further increments of drug treatment were required to control blood pressure of patients receiving oxprenolol than in those receiving methyldopa . The eventual fetal outcome for all patients treated with methyldopa was the same as that for those treated with oxprenolol ;  birth weight , placental weight , head circumference , and Apgar score were not significantly different and there were no stillbirths in either group Abstract . A review is presented as regards the neonatal effects of beta‐blocking agents in hypertension during pregnancy . Experience points to low fetal and neonatal risks , but firmly based data concerning the neonates are very scanty . An on‐going double‐blind study is presented in which pregnant women with hypertension are r and omly allocated to either metoprolol or placebo treatment . One of the aims is to study the postnatal adaptation of the infants . The following measurements , recordings and examinations are performed : anthropometric measurements , Apgar score , blood gases and acid‐base status in umbilical ( venous and arterial ) blood , lactate and hypoxanthine in umbilical venous blood , catecholamines in umbilical arterial blood , pulse rate , blood glucose and a quantitative neurobehavioral assessment in the neonatal period Labetalol was compared with methyldopa in a r and omised trial involving 176 pregnant women with mild to moderate hypertension .  Effective blood pressure control ( diastolic pressure below 86 mmHg ) was obtained in a similar proportion of mothers given labetalol or methyldopa , but the addition of a complementary treatment to achieve control was less frequently needed in the labetalol than in the methyldopa group ( 12/91 vs 22/85 p less than 0.05 ) . Side effects were mild and result ed in discontinuation of the r and omised treatment in 1 mother given labetalol . Pregnancy was terminated by intrauterine death in 4 mothers given methyldopa , and one neonate born to a patient allocated to labetalol died at day 1 . The average birthweight and the proportion of premature delivery or of small for gestational age newborns were similar in both treatment groups . Heart rate , blood pressure , respiratory rate and blood glucose did not differ between infants born to the mothers of the labetalol and the methyldopa groups , irrespective of gestational age at birth or birthweight . Blood pressure control is more frequently achieved in hypertensive pregnancies with labetalol than with methyldopa as a first line treatment . Labetalol is safe to the fetus and newborn and might offer a better prevention of intrauterine death than methyldopa Cord blood IgE levels and the development of allergy were studied in 29 children born by mothers who had been treated with the beta-adrenergic receptor blocking agent , metoprolol , during the pregnancy and in 23 children of placebo-treated mothers . In 13 ( 45 % ) of the former and 3 ( 15 % ) of the placebo group elevated cord blood IgE levels , i.e. more than 0.9 kU/l and /or obvious or probable allergy developed ( p = 0.03 ) . The findings support previous experimental observations that beta-blocking agents may enhance IgE antibody formation . It also adds to the number of environmental factors that may increase the risk for atopic disease in children Objective To determine the need for , and efficacy of , treatment with labetalol in women with mild‐to‐moderate pregnancy induced hypertension ( PIH ) We describe the results of a prospect i ve study in which 120 women who developed hypertension in the last trimester of pregnancy were r and omly allocated in double blind manner to atenolol or placebo . The mean duration of treatment was five weeks . The only difference between groups during the neonatal period was in respiratory distress syndrome , mainly related to spontaneous premature labour , which occurred in six placebo group babies but in none from the atenolol group . Fifty five children from each group have been followed to 1 year of age . All in the atenolol group are developing normally but one child from the placebo group is brain damaged . These findings do not suggest any short or medium term paediatric complications after the use of beta blockers in pregnancy OBJECTIVE To evaluate the short-term effects of intravenously given atenolol and pindolol on utero- and umbilicoplacental vascular impedance , fetal hemodynamics and cardiac function in patients suffering from pregnancy-induced hypertension . STUDY DESIGN A total of 24 women were r and omized to receive atenolol or pindolol infusion . By using pulsed color Doppler techniques , uterine , placental arcuate , umbilical fetal middle cerebral and renal arteries were examined before , at the end and 30 min after the end of infusion . Pulsatility indices ( PI ) were calculated to assess vascular impedance . Fetal myocardial function was evaluated by using pulsed Doppler and M-mode echocardiography . Peak systolic velocities from the ascending aorta and pulmonary trunk , and also inner diameters and fractional shortenings of both ventricles were measured . RESULTS Both drugs significantly decreased maternal blood pressure . Immediately after the infusion , maternal heart rate was significantly decreased in both groups ; but the decrease was clearer and lasted longer in the atenolol group . Pindolol caused no changes in utero- or umbilicoplacental vascular impedance , while atenolol increased it in the nonplacental uterine artery . After atenolol infusion , PI in the umbilical artery was higher than after pindolol . Pindolol had no effects on fetal hemodynamics , while atenolol decreased PI value in the fetal renal artery . Peak systolic velocity in the pulmonary trunk was decreased after atenolol . Pindolol did not affect the fetal cardiac function . In subgroups with originally increased utero- or umbilicoplacental vascular impedance , the responses in uterine and umbilical vascular impedance and in fetal hemodynamics and cardiac function after atenolol and pindolol were different compared to whole groups . CONCLUSION Differently acting antihypertensive agents seem to affect differently uteroplacental vascular impedance .  Atenolol may have some direct effects on fetal hemodynamics and cardiac function . According to our results , pindolol seems to be more preferable in the treatment of pregnancy-induced hypertension than atenolol OBJECTIVE To determine if assessment of maternal hemodynamics could predict women at risk for the development of preeclampsia , if treatment directed at hemodynamic abnormalities before the onset of hypertension could prevent preeclampsia , and if mothers could be treated in a way that protects fetal growth . METHODS A double-blinded , r and omized controlled trial was conducted . Subjects were considered to be at risk for preeclampsia if their cardiac output was greater than 7.4 L/min before 24 weeks ' gestation . Nulliparous and diabetic subjects at risk were treated with 100 mg of atenolol or placebo .  Cardiac output was measured by Doppler technique . Inulin and para-aminohippurate clearances were performed . RESULTS Treatment with atenolol reduced the incidence of preeclampsia from 5 of 28 ( 18 % ) to 1 of 28 ( 3.8 % ) , ( P = .04 ) . Nulliparous women determined to be at risk for preeclampsia were similar to diabetic women at risk . Each was significantly heavier and had inulin and para-aminohippurate clearances greater than the control group . Treatment with atenolol was associated with infants weighing 440 g less than infants in the nulliparous placebo group , ( P = .02 ) . No effect on birth weight was seen in the diabetic patients . Mothers of the smallest infants who were treated with atenolol could be identified by unexpectedly large reductions in cardiac output . CONCLUSION Measurement of cardiac output in the second trimester identified women at risk for preeclampsia . Treatment with atenolol decreased the incidence of preeclampsia .  Nulliparous and diabetic women at risk for preeclampsia were similar with regard to maternal hemodynamics , maternal weight , and renal function . Treatment with atenolol was associated with reduced infant birth weight Eclampsia remains a rare , but serious , complication of pregnancy , estimated to complicate around 1 in 2000 deliveries in Europe and other developed countries ( Douglas & Redman 1992 ) , and from 1 in 100 to 1700 deliveries in developing countries ( Crowther 1985 ; WHO lnternational Collaborative Study of Hypertensive Disorders of Pregnancy 1988 ) ; eclampsia is associated with 10 % of maternal deaths and approximately 50000 women die each year having had an eclamptic convulsion ( Duley 1992 ) . Much of the recent debate about management of women with eclampsia has focused on control of convulsions .  Anticonvulsants are given to prevent the first fit in women who have fulminating pre-eclampsia and to prevent further convulsions in women who already have had an eclamptic fit . Although these indications are related , women who have pre-eclampsia are likely to be less sick than those with eclampsia . The potential for benefit or for harm will , therefore , be different , and the effectiveness of anticonvulsants should be evaluated separately for these two situations . For well over half a century , magnesium sulphate has been advocated for the care of women with pre-eclampsia and eclampsia , yet its use remains controversial ( Donaldson 1992 ) . In the past , the lack of a sound hypothesis for the mechanism by which magnesium sulphate might act as an anticonvulsant has contributed to this . Recent plausible suggestions are that it may act by vasodilatation and subsequent reduction of cerebral ischaemia ( Belfort & Moise 1992 ) ; an alternative is by blocking some of the neuronal damage associated with cerebral ischaemia ( Goldman & Finkbeiner 1988 ) . Reflecting ongoing uncertainty about its role , use of magnesium sulphate continues to vary enormously . In the United States , for example , magnesium sulphate is the anticonvulsant of choice for women with either eclampsia or pre-eclampsia ( Consensus Report 1990 ) , while in the United Kingdom it is used by only 2 % of obstetricians ( Hutton et al. 1992 ) . What is the evidence that magnesium sulphate given to women with either pre-eclampsia or eclampsia does more good than harm ? The popularity of . magnesium sulphate in North America ( and elsewhere ) is largely based on reports of a few hundred women with eclampsia who were treated with magnesium sulphate  ( Pritchard et al. 1984 ) . Whilst sometimes impressive in the number of women included , none of these reports included any form of comparison or control group . Without comparison , it is impossible to know whether the good or bad outcome for the women was due to magnesium sulphate or to a combination of other factors , such as the severity of disease , health status of the women , or to additional interventions . The effectiveness of an intervention , such as magnesium sulphate , is best evaluated by systematic review of all relevant r and omised trials . In the perinatal field , a system for preparing and maintaining review s of the effects of health care already exists ( Cochrane Pregnancy and Childbirth Data base 1993 ) . The evidence presented here is derived from review s published on this data base Thirty-two consecutive women with pregnancy-induced hypertension of early onset were r and omly allocated to treatment with pindolol or methyldopa . There was no difference between the groups in regard to the average time of delivery ( 36.33 vs. 36.6 weeks ) and weight of the newborn ( 2850 vs. 2870 g ) . A significant drop in systolic ( P less than 0.005 ) and diastolic ( P less than 0.05 ) blood pressure was observed in the group of patients treated with pindolol as compared with the methyldopa group . In the pindolol group an improvement in renal function was observed as determined by CCT and serum creatinine . There were no side effects from the drugs in the mother or in the newborn Fifty-three pregnant women with moderately severe hypertension were r and omly allocated to treatment with methyldopa or oxprenolol . There were no significant differences between the groups in age , height , weight , parity , or stage of gestation at the start of treatment . The outcome of pregnancy was better in the group treated with oxprenolol , with greater maternal plasma volume expansion and placental and fetal growth . No intrauterine deaths occurred in either group , and antepartum fetal distress , detected by oxytocin challenge testing , was evident in only one patient , who received methyldopa . This infant , and one other in the methyldopa group , died in the neonatal period . No neonatal deaths occurred in the oxprenolol-treated group . Even in this small number of patients these results were considerably better than those in untreated women with hypertension of similar severity . Apgar scores in both groups were equivalent at birth , while blood sugar concentrations were higher in the oxprenolol group . Oxprenolol appears to be safe and effective in controlling hypertension during pregnancy . There was no evidence of harmful effects on the fetus , and oxprenolol may offer a selective advantage over methyldopa for fetal growth and wellbeing in utero
target: Beta-blockers appear to be no more effective and probably equally as safe .
  It is unusual for women to change drugs due to side effects .
  REVIEW ER 'S CONCLUSIONS Improvement in control of maternal blood pressure with use of beta-blockers would be worthwhile only if it were reflected in substantive benefits for mother and /or baby , and none have been clearly demonstrated .
  Large r and omised trials are needed to determine whether antihypertensive therapy in general ( rather than beta-blocker therapy specifically ) results in greater benefit than risk , for treatment of mild-moderate pregnancy hypertension .
background: BACKGROUND Antihypertensives , such as beta-blockers , are used for pregnancy hypertension in the belief these will improve outcome for mother and baby .
  OBJECTIVES To assess whether oral beta-blockers are better than placebo , or no beta-blocker , and have advantages over other antihypertensives , for women with mild to moderate pregnancy hypertension .