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Antihypertensive drug therapy for mild to moderate hypertension during pregnancy

  1. Edgardo Abalos1,*,
  2. Lelia Duley2,
  3. D Wilhelm Steyn3

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 6 FEB 2014

DOI: 10.1002/14651858.CD002252.pub3


How to Cite

Abalos E, Duley L, Steyn DW. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD002252. DOI: 10.1002/14651858.CD002252.pub3.

Author Information

  1. 1

    Centro Rosarino de Estudios Perinatales (CREP), Rosario, Santa Fe, Argentina

  2. 2

    Nottingham Health Science Partners, Nottingham Clinical Trials Unit, Nottingham, UK

  3. 3

    University of Stellenbosch, Obstetrics & Gynaecology, Tygerberg, Stellenbosch, South Africa

*Edgardo Abalos, Centro Rosarino de Estudios Perinatales (CREP), Moreno 878, 6th floor, Rosario, Santa Fe, S2000DKR, Argentina. edgardoabalos@crep.org.ar. crep@crep.org.ar.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 6 FEB 2014

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Characteristics of included studies [ordered by study ID]

MethodsAllocation concealment: not stated. Authors said '...randomly divided into two groups...'.


Participants60 women with SBP >/= 160 mmHg and/or DBP >/= 100 mmHg x 2, 24 hr apart, with or without proteinuria at trial entry.
Excluded: > 1 drug to control BP, or contraindication for beta blockers.


InterventionsExp: atenolol 50-250 mg/day.
Control: methyldopa 750-2000 mg/day.


OutcomesWomen: BP (mean).
Babies: gestational age, birthweight, Apgar score, stillbirth, neonatal deaths.


NotesMain paper in Spanish. Methods for measuring BP not mentioned.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomly divided into two groups..." no further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said 'open randomised study'.


Participants20 women with SBP > 159 mmHg and/or DBP > 99 mmHg x 2, 24 hr apart, +/- proteinuria.
Excluded: > 1 drug to control BP, or hypertensive emergency.


InterventionsExp: ketanserin 20-80 mg/day.
Control: methyldopa 500-2000 mg/day.


OutcomesWomen: none reported.
Babies: stillbirth, neonatal death, birthweight (mean), gestation at delivery (mean).


NotesInterim report of study ongoing in 1987. Methods for measuring BP not mentioned.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...open randomised study..." no further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: not stated. Authors said 'randomised' 'divided into 2 equal groups'.


Participants36 women > 14 weeks' gestation with BP >/= 140/90 mmHg and </= 170/110 mmHg.


InterventionsExp: mepindolol, increasing weekly doses, from 5-10 mg/day.
Control: methyldopa, increasing weekly doses from 500-2000 mg/day.


OutcomesWomen: additional antihypertensive, caesarean section, side-effects, maternal complications.
Babies: stillbirth, SGA (undefined).


NotesMethods for measuring BP not mentioned. Available only as an abstract.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomised study..." no further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study abstract.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said 'randomly allocated'.


Participants28 women in antenatal clinics with mild-moderate PIH (BP >/= 140/90 mmHg x 2 at least 24 hr apart).
Excluded: impaired renal function.


InterventionsExp: propranolol 30-160 mg/day.
Control: methyldopa 500-1000 mg/day.


OutcomesWomen: severe hypertension, proteinuria (undefined), additional antihypertensive, changed drugs due to side-effects, caesarean section.
Babies: perinatal death, preterm delivery, jaundice, bradycardia, hypoglycaemia, birthweight (mean).


NotesLondon School of Hygiene sphygmomanometer (random zero) used. No mention of which Korotkoff sound used for DBP.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomly allocated..." no further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said 'allocated by series of random numbers'.


Participants183 women with singleton pregnancy and mild hypertension (DBP >/= 90 mmHg x 2, 24 hr apart, or DBP >/= 95 mmHg x 2, 12 hr apart, or DBP >/= 100 mmHg x 2, 8 hr apart).


InterventionsExp: oxprenolol 40-320 mg x 2/day.
Control: methyldopa 250 mg x 2/day-1000 mg x 3/day.

If blood pressure not controlled, hydralazine in both groups.


OutcomesWomen: severe hypertension, proteinuria ('heavy and increasing requiring delivery'), additional antihypertensive, induction of labour, caesarean section,
Babies: stillbirth, neonatal death, admission to SCBU, days in SCBU, RDS, birthweight. (mean), Apgar (mean).


NotesKorotkoff phase IV used for DBP.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described: "...were allocated by a series of random numbers to...", no further details.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasHigh riskCointerventions: 48% of oxprenolol group and 35% of methyldopa group received a second or third antihypertensive.


MethodsAllocation concealment: central telephone randomisation Although authors stated it was a placebo-controlled trial, data provided by authors suggest that they may have used a patch for the control, but not a matching placebo.


Participants16 women with gestational hypertension, defined as "de novo" hypertension after 20 weeks' gestation of > 140 and/or 90 mmHg on 2 readings, 6 hr apart; or a rise in systolic pressure of > 25 mmHg or a diastolic of 15 mmHg from a BP pre-pregnancy or in the first trimester.


InterventionsExp: transdermal glyceryl trinitrate patches 10 mg.
Control: patch for the control, but not a matching placebo.


OutcomesWomen: pre-eclampsia, side-effects.
Babies: not reported.


NotesTrial planned to recruit 220 women and stopped early due to side-effects (headache) in the treatment group. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding of participants and personnel (performance bias)
All outcomes
High riskDescribed as "...single blind, placebo controlled trial...".

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study letter to editor.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said '...patients were randomly divided into two groups...'.


Participants100 women with chronic hypertension diagnosed before 20th week, BP >/= 140/90 mmHg x 2, 5 min apart. With no proteinuria and no contraindication to beta blockers.


InterventionsExp: pindolol 10-30 mg/day.
Control: no treatment.


OutcomesWomen: MAP, severe pre-eclampsia, side-effects.
Babies: abortions, fetal deaths, neonatal deaths, gestational age, birthweight, IUGR, Apgar score, congenital malformations, hypoglycaemia.


NotesMethods for measuring blood pressure not mentioned. Main paper in Portuguese.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: : "...patients were randomly divided into two groups...", no further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: consecutive numbered treatment boxes.


Participants40 pregnant women with chronic hypertension with DBP =/> 95 mmHg, without proteinuria.


InterventionsExp: pindolol 10-30 mg/day.
Control: methyldopa 500-2000 mg/day.


OutcomesWomen: BP, need for additional antihypertensives, severe HT, superimposed pre-eclampsia.
Babies: birthweight, Apgar score, fetal and neonatal death, preterm birth, SGA (undefined).


NotesMain paper in Portuguese. Methods for measuring BP not mentioned. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot stated.

Allocation concealment (selection bias)Low riskConsecutive numbered treatment boxes (personal communication).

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Low riskPublished and unpublished data provided by author.

Other biasUnclear risk.


MethodsAllocation concealment: trial drug supplied by pharmacy in packs with serial numbers.
Withdrawals: 15 women (7.5%) excluded from the analysis (5 delivered in other hospitals, 9 dropped the study or failed to comply with treatment, 1 due to side-effects).


Participants199 singleton pregnant women with mild/moderate chronic hypertension (DBP > 90 mmHg and =/< 110 mmHg before 20 weeks' gestation, or with history of chronic hypertension), before 25 weeks' gestation and giving informed consent. Excluded: renal, cardiac or hepatic disease, IUGR diagnosed before trial entry, alcohol/drug abuse.


InterventionsExp: verapamil 240 mg x 3/day.
Control: placebo.


OutcomesWomen: BP, heart rate, severe hypertension, superimposed pre-eclampsia, side-effects, mode of delivery.
Babies: birthweight, gestational age, SGA, Apgar score, jaundice, hypoglycaemia, mortality.


NotesKorotkoff phase IV used for DBP. Main report in Portuguese, presented as a Doctoral Thesis. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Low riskConsecutive numbered treatment packs containing the study drug or placebo.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind, only pharmacist providing treatment packs aware of the codes.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble blind, only pharmacist providing treatment packs aware of the codes.

Incomplete outcome data (attrition bias)
All outcomes
Low risk15 withdrawals (7.5%): 5 women delivered in other hospitals, 10 withdrew consent (1 due to side-effects).

Selective reporting (reporting bias)Unclear riskAssessment from published study thesis.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: women given number corresponding to sealed envelope and treatment batch. Envelope contained unblinding, kept by investigator and only opened when necessary. Envelopes collected at end of study. 2 centres.
Withdrawals: 1 woman, from placebo group.


Participants155 women with singleton pregnancy at 20-36 weeks' gestation, DBP < 85 mmHg x 2 before 20 weeks and > 84 mmHg after 20 weeks.
Excluded: type I diabetes, congestive heart failure, cardiac block, asthma, pre-pregnancy hypertension, antihypertensive treatment during current pregnancy.


InterventionsExp: oxprenolol 160-320 mg x 2/day. Hydralazine 50-100 mg added if necessary to keep DBP < 86 mmHg.

Control: placebo, identical appearance.


OutcomesWomen: death, mean BP, severe hypertension, proteinuria (> 1+ or 0.25 g/L), additional antihypertensive, eclampsia, changed drugs due to side-effects, elective delivery, caesarean section, hospital admission, days in hospital, placental abruption.
Babies: perinatal death, preterm delivery (< 37 weeks), birthweight (mean), SGA (undefined, excludes stillbirth), 5 min Apgar < 7, admission to SCBU, RDS.


NotesKorotkoff phase IV used for DBP. For 23 women (15%), treatment unblinded and other treatment started. 16 for uncontrolled BP (5 exp, 11 control) and 7 for poor compliance/side-effects (4 exp, 3 control). Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomisation was in stratified blocks of ten..."

Allocation concealment (selection bias)Low risk"...sealed envelopes and individual batch of drugs containing either the maximum amount of active drug that could be used in 20 weeks of treatment or placebos of identical appearance."

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind, placebo controlled.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskYes.

Incomplete outcome data (attrition bias)
All outcomes
Low risk1 women (0.6%) lost to follow-up.

Selective reporting (reporting bias)Low riskPublished and unpublished data provided by author.

Other biasHigh riskFor 23 women (15%), treatment unblinded and other treatment started. 16 for uncontrolled BP (5 exp, 11 control) and 7 for poor compliance/side-effects (4 exp, 3 control).


MethodsAllocation concealment: 'blinded envelopes'. Stratified in blocks of 10 at each clinic. Multicentre, 12 hospitals.
Withdrawals: 12 women (6%). 5 labetalol (3 lost to follow-up and 2 given methyldopa) and 7 methyldopa (all lost to follow-up).


Participants188 women with singleton pregnancy at 12-34 weeks' gestation, booked < 20 weeks and DBP >/= 90 mmHg.
Excluded: previous antihypertensive treatment this pregnancy, diabetes, depression, contraindication to beta blockers.


InterventionsExp: labetalol 200-600 mg x 2/day.
Control: methyldopa 250-750 mg x 2/day.


OutcomesWomen: proteinuria (> 2+ or 0.5 g/L), admission to hospital, caesarean section, elective delivery, additional antihypertensive, side-effects, changed drugs due to side-effects.
Babies: stillbirth, neonatal death, admission to SCBU, SGA (< 5th centile, excludes stillbirths), preterm delivery (< 37 weeks), 5 min Apgar < 8.


NotesKorotkoff phase IV used for DBP.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"...stratified blocks of ten at each clinic..."

Allocation concealment (selection bias)Low riskBlinded envelopes.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low risk12 women (6.4%) excluded from analysis: 10 lost to follow-up (3 from labetalol and 7 from methyldopa group), and 2 "protocol violation".

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: not stated. Authors said 'random order'.
3-arm study.


Participants63 women at 7-36 weeks' gestation with DBP > 90 mmHg x 2, 8 days apart).


InterventionsExp: (1) acebutolol 400-1200 mg; (2) labetalol 400-1200 mg.
Control: methyldopa 500-1500 mg.


OutcomesWomen: PE, caesarean section.
Babies: perinatal death, preterm delivery, birthweight (mean), Apgar, admission to SCBU, hypoglycaemia.


NotesNo mention about Korotkoff sound considered for DBP. Main paper in French.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Apres tirage au sort, effectué par groupe de 9 patientes..."

Allocation concealment (selection bias)Unclear riskNot described.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: sealed envelopes drawn by physician. Ordered using list of computer-generated random numbers.


Participants100 women with singleton pregnancy at > 20 weeks' gestation and mild-moderate hypertension (BP >/= 140/90 mmHg x 2). No other antihypertensive medication at trial entry.


InterventionsExp: nicardipine 20 mg x 3/day.
Control: metoprolol (slow release) 200 mg/day.


OutcomesWomen: severe hypertension, proteinuria (undefined), HELLP syndrome, additional antihypertensive, changed drug due to side-effects, induction of labour, caesarean section.
Babies: perinatal death, umbilical Doppler, admission to SCBU.


NotesKorotkoff phase IV used for DBP.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskList of computer-generated random numbers.

Allocation concealment (selection bias)Low riskSealed envelopes.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: not stated.
Authors said: 'randomised double-blind'.


Participants41 healthy nulliparous women admitted for PE (BP >/= 140/90 mmHg x 2 within 24 hours).


InterventionsExp: labetalol 200 mg x 3/day.
Control: placebo (character not stated).


OutcomesWomen: mean BP, severe hypertension, additional antihypertensive.
Babies: birthweight (mean), SGA (< 10th centile), gestation at delivery (mean).


NotesTrial reported as in progress in 1990. Missing data for some babies. No description of how BP measured. Available only as an abstract.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: authors only said: 'randomised double-blind controlled study'.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind, placebo controlled.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskYes.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study abstract.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said 'randomly allocated'.


Participants30 primigravid women at 24-37 weeks' gestation with mild-moderate PIH (BP>/ = 140/90 mmHg x 2, 6 hr apart).
Excluded: UTI, heart disease or other cause of hypertension.


InterventionsExp: metoprolol 50-150 mg x 2/day.
Control: methyldopa 250 mg x 3/day, increased to 2000 mg/day.


OutcomesWomen: severe hypertension.
Babies: perinatal death, preterm delivery, gestation at delivery, birthweight, Apgar at 1 and 5 min (mean).


NotesMethod for measuring BP not mentioned.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomly allocated...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsMethods not stated, authors only say "...randomised by number..."


Participants118 primigravid women with hypertension (BP > 140/90 x 2, 60 hours apart) during pregnancy with and without proteinuria at > 20 weeks' gestation.

Excluded: 2nd or more pregnancies, history of chronic HT, use of anti HT drugs.


InterventionsExp: Nimodipine 30 mg every 6 hours.

Control: Methyldopa 250 mg every 6 hours.


OutcomesMAP, additional antihypertensives, serum creatinine and liver enzymes, induction of labour, serious maternal side-effects, perinatal deaths.


NotesMethod for measuring BP not mentioned.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomised by number...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low risk7 dropouts (6%), not specified in which group.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsMixed sealed envelopes containing the assigned intervention. 3-arm trial.


Participants149 women with PIH (140-159/90-109 mmHg x 2, 6 hours apart, without proteinuria) at 20-38 weeks' gestation.

Excluded: chronic HT, previous anti HT medication, secondary HT, UTI, diabetes, known medical/psychiatric disorders, multiple pregnancy, placenta previa, Rh isoimmunisation, congenital abnormality.


InterventionsExp 1: Labetalol 100 mg x 2/day (up to 2500 mg).

Exp 2: Methyldopa 250 mg x 2/day (up to 2000 mg).

Control: no treatment.


OutcomesBP, laboratory parameters, gestational age at delivery, birthweight, 5 min Apgar score, maternal adverse events, maternal death, major morbidity, severe HT, proteinuria, severe pre-eclampsia, antenatal hospital admission, caesarean section, perinatal death, SGA, preterm babies, Admission to NICU.


NotesKorotkoff phase V for DBP.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High risk"Allocation cards labelled L (labetalol), M (methyldopa) or N (no antihypertensive) were prepared by a staff clerk in equal numbers of 50 each and put into opaque envelopes that were subsequently sealed, mixed up and numbered 1-150."

Allocation concealment (selection bias)Low riskConsecutively numbered opaque sealed envelopes.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low risk1 woman withdrew consent in methyldopa group.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


Methods"...patients were divided into two groups randomly..."


Participants180 pregnant women at > 20 weeks' gestation with BP > 140/90 mmHg x 2, 6 hours apart and proteinuria 1+ on dipstick x 2, 4 hours apart.


InterventionsExp: Labetalol 100 mg t.i.d. (doubled every 48 hours until BP control).

Control: Methyldopa 250 mg t.i.d. (doubled every 48 hours until BP control).


OutcomesFall in BP after 7 days treatment, average dose of drug used, induction of labour, maternal side-effects.


NotesMethod for measuring BP not mentioned.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...patients were divided into two groups randomly...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: cards with 'test' or 'control' sealed in envelopes, shuffled and then numbered in sequence. Consecutive envelopes opened.


Participants36 women < 38 weeks' gestation with BP >/= 140/90 mmHg on 2 separate days, without proteinuria.
Excluded: if lived too far from the hospital to attend for frequent examinations.


InterventionsExp: choice between atenolol 50-100 mg/day and methyldopa 750-2250 mg/day. If monotherapy inadequate, 2 drugs combined. Bendrofluazide 2.5-5.0 mg added as a third agent when necessary.
Control: no antihypertensive.


OutcomesWomen: MAP, proteinuria.
Babies: perinatal death, Apgar, gestation age at delivery, birthweight, birthweight < 50th centile.


NotesKorotkoff phase V used for DBP. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High risk"...shuffled into random order..."

Allocation concealment (selection bias)Low riskSealed, identical numbered envelopes.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: not stated. Authors said 'randomly allocated'.


Participants32 women with singleton pregnancy at 27-33 weeks' gestation with PIH (DBP >/= 95 mmHg x 2 at least 6 hr apart).
Excluded: history of chronic renal disease or essential hypertension.


InterventionsExp: pindolol 15 mg/day.
Control: methyldopa up to 2000 mg/day (no other details).


OutcomesWomen: severe hypertension, new proteinuria (> 2+ or 0.5 g/L), eclampsia, side-effects, additional antihypertensive, changed drugs due to side-effects.
Babies: neonatal death, birthweight (mean), abnormal antenatal fetal heart rate, gestation at delivery (mean).


NotesMethods for BP measurement not mentioned.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomly allocated...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: not stated. Authors said 'randomly allocated'.
2 women with side-effects on hydralazine crossed over to pindolol + hydralazine, and reported in this group. Data only included if available as intention-to-treat.


Participants44 women at < 37 weeks with BP >/= 150/90 mmHg x 2 at least 24 hr apart.
Excluded: insulin-dependent diabetes, obstructive lung disease, contraindication to pindolol or hydralazine.


InterventionsExp: hydralazine 50-100 mg/day + pindolol 10-25 mg/day (in 2 daily doses).
Control: hydralazine 50-100 mg/day (in 2 daily doses).


OutcomesWomen: severe hypertension, proteinuria (> 1 g in 24 hr), side-effects, changed drug due to side-effects, caesarean section.
Babies: preterm delivery, SGA (< 250 on Usher's curve), hypoglycaemia, hypothermia, low Apgar score.


NotesNo mention of which Korotkoff sound used.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomly allocated...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline. 2 women with side-effects on hydralazine crossed over to pindolol + hydralazine, and reported in this group. Data only included if available as intention-to-treat.


MethodsAllocation concealment: trial drug supplied by pharmacy in packs with serial numbers, in blocks of 6.


Participants60 women < 35 weeks' gestation with DBP 85-99 mmHg x 2, 12 hours apart, and no treatment for hypertension during this pregnancy.
Excluded: multiple pregnancy, contraindication to beta blockers or insulin-dependent diabetes.


InterventionsExp: pindolol 5 mg x 2/day. If DBP still >/= 85 mmHg on day 3, increased to 5 mg x 3/day, if no response next day, increased to 10 mg x 2/day.
Control: identical placebo.

If DBP 100-109 mmHg x2 or > 110 mmHg x1, hydralazine added for pindolol group. In placebo group, pindolol given first, followed by hydralazine if DBP > 100 mmHg.


OutcomesWomen: additional antihypertensive, days in hospital, proteinuria > 2+ or > 0.5 g/L, treatment stopped due to side-effects, caesarean section.
Babies: perinatal death, gestation at delivery (mean), birthweight, 5 min Apgar > 7, SGA (< 10th centile), hypoglycaemia, jaundice.


NotesKorotkoff IV used for DBP.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"...in a random fashion, in blocks of six, using serial numbers..."

Allocation concealment (selection bias)Low riskPindolol and placebo tablets supplied by pharmacy in numbered packets.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind : "...placebo of identical appearance...".

Blinding of outcome assessment (detection bias)
All outcomes
Low riskCodes were broken only in the presence of severe side-effects.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: not stated. Authors said 'randomly allocated'.
3-arm trial.


Participants51 women with BP 140-160/95-110 mmHg.
Excluded: proteinuria > 2+, contraindication to beta blockers, or any other disease.


InterventionsExp: (1) hydralazine 60-200 mg/day + propranolol 40-120 mg/day; (2) hydralazine 60-200 mg/day + pindolol 5-15 mg/day.
Control: hydralazine 60-200 mg/day.


OutcomesWomen: eclampsia, severe maternal morbidity, side-effects, caesarean section.
Babies: perinatal death, preterm delivery, SGA (< 10th centile), birthweight (mean).


NotesKorotkoff phase V used for DBP.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomly allocated...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said: 'randomly allocated'.


Participants100 primigravid women at 26-36 weeks' gestation with SBP 140-160 mmHg, and DBP 90-110 mmHg in first 24 hr after admission and proteinuria < 300 mg/24 hr.
Excluded: if other medical maternal or fetal pathology (IUGR or altered biophysical profile).


InterventionsExp: nifedipine 40-120 mg/day orally and bed rest.
Control: bed rest alone.


OutcomesWomen: severe hypertension, proteinuria, days in hospital before delivery.
Babies: stillbirth, neonatal death, gestation at delivery (mean), birthweight, placental weight, SGA (undefined).


NotesMethods for measuring blood pressure not stated. Article in Italian.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomly allocated...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: central telephone randomisation, stratified by centre and type of hypertension (chronic, gestational or unclassified). Multicentre, 33 hospitals.
Withdrawals: 22 women (8%), 13 exp and 9 control lost to follow-up.
Follow-up of children at 18 months: 190/252 (77%) responded to postal survey.


Participants283 women at 12-34 weeks' gestation, with mild-moderate hypertension (DBP 90-110 mmHg x 2, 4 hours apart).
Excluded: chronic diseases (such as diabetes or renal disease), fetal malformations, previous antihypertensive treatment or contraindications to nifedipine.


InterventionsExp: slow-release nifedipine 20-80 mg x 2/day orally.
Control: no antihypertensive.


OutcomesWomen: severe hypertension, proteinuria, caesarean section, admission to intensive care.
Babies: perinatal death, birthweight, SGA (< 10th centile), preterm delivery (< 34 and < 37 weeks), admission to SCBU, hyperglycaemia, jaundice, RDS, other serious neonatal problems.


NotesClassification of hypertensive disorders using Davey and MacGillivray system. Methods for measuring blood pressure not mentioned.
Data from follow-up excluded as > 20% lost.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random numbers balanced by centre and stratified by type of hypertension.

Allocation concealment (selection bias)Low riskAllocation by telephone.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low risk22 women (7.8%) lost to follow-up.13 in nifedipine group and 9 in control group.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: consecutive-numbered, opaque, sealed envelopes. 3-arm study. 6 women (17%) left the study due to side-effects (2 women) or mother's or baby's worsening conditions (4).


Participants36 women with singleton pregnancy, gestation > 24 weeks and PIH or PE (BP 140/90 mmHg or more, PE if proteinuria > 300 mg/24 hr).
Excluded: fetal abnormalities or chromosomal disorders, renal or hepatic disease, chronic hypertension.


InterventionsExp (1): transdermal glyceryl trinitrate 10 mg continuously 24 hr/day. Exp (2): transdermal glyceryl trinitrate 10 mg intermittently for 16 hr/day.
Control: Nifedipine 40 mg/day orally.


OutcomesWomen: caesarean section, BP (mean), stopped drug due to side-effects, severe hypertension, proteinuria/pre-eclampsia.
Babies: birthweight, fetal/neonatal deaths, preterm birth, IUGR, gestation at birth (mean).


NotesKorotkoff phase IV used for DBP. In the analysis the 2 GTN arms have been combined. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Low riskConsecutive opaque sealed envelopes (personal communication).

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
High risk6 withdrawals (16.6%). 3 in group 1, 1 in group 2 and 2 in group 3.

Selective reporting (reporting bias)Low riskAdditional data provided by authors.

Other biasUnclear risk.


MethodsAllocation concealment: consecutive-numbered treatment boxes.


Participants20 women with pre-eclampsia (no further details).


InterventionsExp: nifedipine GITS 30-60 mg/day.
Control: methyldopa 500-1000 mg/day.


OutcomesWomen: BP, PE, Doppler abnormalities, need for drug adjustment, severe hypertension.
Babies: fetal and neonatal death, preterm birth, SGA (undefined), Apgar score.


NotesPublished as an abstract only. Method for measuring BP not stated. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Low riskConsecutive numbered treatment boxes provided by pharmacy (personal communication).

Blinding of participants and personnel (performance bias)
All outcomes
High riskSingle blind (only for participants).

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Low riskAdditional data provided by authors.

Other biasUnclear risk.


MethodsAllocation concealment: cards labelled R and Q picked blindly from a box, these identified drug container.


Participants32 women at 12-30 weeks' gestation with a singleton pregnancy and BP >/= 140/90 mmHg x 2 at least 6 hr apart, no proteinuria, no antihypertensive therapy and no other drug treatment.


InterventionsExp: prazosin 1-5 mg x 3/day.
Control: identical placebo.


OutcomesWomen: severe hypertension, proteinuria, duration of treatment, placental abruption, caesarean section.
Babies: perinatal death, gestation at delivery (mean), birthweight, SGA (< 10th centile) preterm delivery (< 37 weeks).


NotesMethod for measuring blood pressure not mentioned. The trial stopped early.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...in a randomised way, participants either received...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskAlthough identical placebo tablets were used, there is no information about whether it was a double-blind or a single-blind trial.

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said: 'randomised open study'.
Withdrawals: 3 women (10%) lost to follow-up, but outcome for babies reported.


Participants29 women at 29-36 weeks' gestation with mild-moderate hypertension (DBP 90-110 mmHg).


InterventionsExp: nifedipine started at 30 mg/day.
Control: methyldopa started at 750 mg/day.

Stated that 'dose adjustments were made, when necessary, every second day until control of BP was obtained'.


OutcomesWomen: additional antihypertensive, caesarean section, induction of labour, side-effects.
Babies: stillbirth, preterm delivery, gestation at delivery (mean), admission to SCBU.


NotesMethod for measuring BP not mentioned.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomised, prospective open study...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
High risk3 women (10.3%) did not complete the trial. 2 from one group and 1 from the other, not clear from the report in which group they were.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said: '...patients were randomly allocated...'.


Participants70 primigravid women with pre-eclampsia (BP =/> 90/109 mmHg x 2, 6 hr apart plus 2+ proteinuria in dipsticks) at 28-36 weeks' gestation. Singleton pregnancy.


InterventionsExp: methyldopa 750-4000 mg/day
Control: no drug treatment.

All women in both groups were admitted to hospital for bed rest.


OutcomesWomen: BP, abruptio, imminent eclampsia, eclampsia, preterm delivery, caesarean section, maternal death.
Babies: birthweight, IUGR, admission to SCBU (reported as 'referral of baby'), perinatal deaths, Apgar score.


NotesKorotkoff IV sound used for DBP.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...patients were randomly allocated...".

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: telephone randomisation, no further details.


Participants52 women in antenatal clinic at < 37 weeks' gestation with singleton pregnancy, BP >/= 140/90 mmHg or an increase of at least 30 mmHg SBP or 15 mmHg DBP x 2 within 24 hr.
Excluded: imminent eclampsia, serious fetal distress, severe hypertension (> 170/110 mm Hg), Rh disease, diabetes, contraindication to beta blockers, 'social or psychological handicaps'.


InterventionsExp: metoprolol 100-200 mg x 2/day.
Control: identical placebo x 2/day.


OutcomesWomen: proteinuria (>/= 2+), severe hypertension, changed drugs due to side-effects, hospital admission, placental abruption, caesarean section.
Babies: perinatal death, gestation at delivery (mean) Apgar (mean).


NotesKorotkoff phase V used for DBP. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Low riskTelephone randomisation (personal communication).

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind. Placebos of identical appearance.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskYes.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Low riskUnpublished data provided by author.

Other biasUnclear risk.


MethodsAllocation concealment: 'envelope randomisation'. No further information.
Withdrawals: 7 women (4%) dropped out (4 exp, 3 control). Multicentre, not stated how many hospitals.


Participants168 women in antenatal ward with singleton pregnancy at < 37 weeks, DBP >/= 90 mmHg x 2, no proteinuria.
Excluded: diabetes, asthma, heart disease, psychiatric or psychological disorders.


InterventionsExp: metoprolol 50-200 mg/day + hydralazine 50-300 mg/day.
Control: no antihypertensive.


OutcomesWomen: severe hypertension, proteinuria (> 1+ or 0.25 g/L), changed drugs due to side-effects, placental abruption, caesarean section.
Babies: stillbirth, neonatal death, preterm delivery (< 37 and < 34 weeks), SGA (undefined), bradycardia, hypoglycaemia, Apgar < 7 at 1 and 5 min, RDS.


NotesKorotkoff phase V used for DBP. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described "...randomly allocated...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: authors said: 'randomised by numbers to treatment with capsules'. Randomisation in blocks of 6. Information about allocation kept in sealed envelopes, opened if severe complications or side-effects. 5 centres in Sweden, 1 in Denmark.
Withdrawals: 7 women (6%), 1 dropout, 6 not re-evaluated after 3 days (4 exp, 2 control).


Participants118 women at 26-37 weeks, with singleton pregnancy and DBP 95-110 mmHg.
Excluded: if delivery expected within a week, history of alcohol or drug abuse, or other medication known to be toxic.


InterventionsExp: isradipine (slow release) 5 mg x 2/day.
Control: placebo x 2/day.


OutcomesWomen: eclampsia, severe hypertension (DBP >/= 110 mmHg), proteinuria >/=2+, need for additional antihypertensive, MAP, caesarean section, induction of labour, side-effects.
Babies: perinatal death, gestation at delivery (mean), admission to SCBU, birthweight (mean), placental weight.


NotesKorotkoff phase IV used for DBP. Description of BP measurements technique, and of criteria used to define hypertension and proteinuria.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"...by numbers in blocks of 6..."

Allocation concealment (selection bias)Unclear riskNot described: "...parallel double blind study...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskYes.

Incomplete outcome data (attrition bias)
All outcomes
Low risk7 withdrawals (6%).

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: not stated. Authors said 'allocated at random'.


Participants100 pregnant women with DBP >/= 90 mmHg or more x 2, 48 hr apart.


InterventionsExp: methyldopa 250-1,000 mg x 2/day + bendrofluazide 5-10 mg/day.
Control: no treatment.


OutcomesWomen: mean BP, proteinuria, residual hypertension, length of gestation.
Babies: birthweight (mean), perinatal death.


NotesMethods for measuring BP not mentioned. According with BP at entry, women were divided in 2 groups: 'moderate' for those with DBP = or > 90 mmHg at entry (n = 42), and 'severe' for those with DBP = or > 100 mmHg (n = 58). For the main outcomes results are presented together.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...allocated at random...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said 'randomly allocated'.
Withdrawals: 5 women (2%) withdrawn from exp group.
Follow-up of 202 live born children. At 4 years, 34 (17%) lost to follow-up. At 7, years 7 (3%) lost to follow-up.


Participants247 women with BP >/= 140/90 mmHg if < 28 weeks' gestation, or >/= 150/95 mmHg if > 28 weeks' gestation x 2, 24 hr apart.
Excluded: diabetes, multiple pregnancy, Rh immunisation. Women > 36 weeks' gestation excluded during first year of the trial, thereafter excluded if > 32 weeks' gestation.


InterventionsExp: methyldopa 750-4000 mg/day.
Control: no antihypertensive.

Hydralazine if severe hypertension.


OutcomesWomen: severe hypertension, proteinuria, caesarean section, elective delivery, side-effects, changed drug due to side-effects.
Babies: perinatal death, birthweight (mean), gestation at delivery (mean), SGA (< 2 SD below mean), babies nursed in an incubator, neurodevelopment at 4 and 7 years.


NotesKorotkoff phase IV used for DBP. Random zero sphygmomanometer.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "Treatment was allocated randomly...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low risk5 withdrawals (2%).

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: randomly allocated using random-number table.


Participants26 women < 38 weeks' gestation with PIH and no contraindication to beta blockers.


InterventionsExp: labetalol 400-800 mg/day.
Control: methyldopa 750-1500 mg/day.


OutcomesWomen: proteinuria, severe hypertension, caesarean section, induction of labour, side-effects.
Babies: stillbirth, birthweight (mean), gestation at delivery (mean), 1 min Apgar, admission to SCBU, jaundice.


NotesKorotkoff phase IV used for DBP.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number table.

Allocation concealment (selection bias)Unclear riskNot described: "...randomly allocated...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: envelope randomisation, no further information.


Participants126 women with either chronic hypertension or PIH, and DBP > 95 mmHg if < 20 weeks or 95-109 mmHg if > 20 weeks.


InterventionsExp: labetalol 100 mg x 2/day, increased to maximum of 1200 mg/day.
Control: no antihypertensive.

If BP not controlled, hydralazine 25 mg x 3/day, increased to maximum of 200 mg/day.


OutcomesWomen: severe hypertension, proteinuria (undefined), caesarean section, placental abruption.
Babies: perinatal death, SGA (< 10th centile).


NotesMethods for measuring BP not mentioned. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskEnvelope randomisation (personal communication). No details on whether they were opaque, sealed and consecutively numbered.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Low riskAdditional data provided by author.

Other biasUnclear risk.


MethodsAllocation concealment: authors said 'allocated in double-blind and randomised manner'.
Withdrawals: some data missing for 35 women (29%). Data for each outcome only included if < 20% excluded.
Follow-up: 110 children (92%) seen at 1 year.


Participants120 women with PIH in third trimester admitted for bed rest, SBP 140-170 mmHg and DBP 90-110 mmHg x 2, 24 hr apart.
Excluded: women with contraindication to beta blockers.


InterventionsExp: atenolol 100-200 mg/day.
Control: placebo.


OutcomesWomen: proteinuria (> 0.5 g/24 hr), severe hypertension, additional antihypertensive, changed treatment due to side-effects, side-effects, admission to hospital prior to delivery, caesarean section.
Babies: perinatal death, SGA (< 10th centile), bradycardia, hypoglycaemia, jaundice, RDS. At 1 year: cerebral palsy, IQ < 1 SD below mean, weight.


NotesKorotkoff phase IV used for DBP. Random zero sphygmomanometer used for measuring blood pressure.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...allocated in double-blind, randomised manner...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind, placebo controlled.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskYes.

Incomplete outcome data (attrition bias)
All outcomes
Low riskWithdrawals: some data missing for 35 women (29%). Data for each outcome only included if < 20% excluded. Follow-up: 110 children (92%) seen at 1 year.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said 'allocated at random'. Stratified by gestational age.


Participants100 women with singleton pregnancy and DBP >/= 95 mmHg x 2 at least 24 hr apart, or > 105 mmHg x 1.
Excluded: asthma, heart failure, or heart block, diabetes, renal disease, or taking other hypertensive medication.


InterventionsExp: oxprenolol 80-320 mg x 2/day.
Control: methyldopa 250-1000 mg x 3/day.

If BP not controlled, hydralazine added to both groups.


OutcomesWomen: severe hypertension, proteinuria (> trace on dipstick), induction of labour, caesarean section, additional antihypertensive, hospital admission.
Babies: perinatal death, birthweight (mean), 5 min Apgar < 7, antenatal fetal heart rate.


NotesKorotkoff phase IV used for DBP. Random zero sphygmomanometer.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described "...allocated at random...". Stratified by gestational age.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low risk4 women (4%) excluded, 2 lost to follow-up, 2 abortions.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said 'randomised trial'.


Participants60 women at 18-36 weeks' gestation with undefined hypertension.


InterventionsExp: atenolol 100 mg/day.
Control: methyldopa 250 mg x 3/day.


OutcomesWomen: proteinuria (undefined).
Babies: stillbirth, birthweight, SGA (< 10th centile) bradycardia, hypoglycaemia.


NotesKorotkoff phase V used for DBP.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomised trial...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: drug and placebo sent by manufacturer to hospital pharmacy with list of random numbers. Then dispensed by pharmacists. 5 centres.
Withdrawals: 8 (5%), 6 exp, 2 control. 2 women withdrew, 1 treated with ward stock labetalol, 1 developed rash, and 4 did not fulfil entry criteria.


Participants152 women from antenatal wards at 20-38 weeks' gestation with SBP 140-160 mmHg and DBP 90-105 mmHg x 2, 24 hr apart, and no proteinuria.
Excluded: history of hypertension, renal, metabolic, cardiovascular, respiratory or collagen disease.


InterventionsExp: labetalol 100-200 mg x 3/day.
Control: identical placebo.


OutcomesWomen: mean BP, severe hypertension, proteinuria (undefined), induction of labour, caesarean section, days in hospital (mean), side-effects.
Babies: perinatal death, preterm delivery (< 37 weeks), SGA (< 5th centile), admission to SCBU, RDS.


NotesKorotkoff phase IV used for DBP. Conventional sphygmomanometers used to measure blood pressure.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskList of random numbers.

Allocation concealment (selection bias)Low riskDrug and placebo sent by manufacturer to hospital pharmacy with list of random numbers. Then dispensed by pharmacists.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind, placebo controlled.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskYes.

Incomplete outcome data (attrition bias)
All outcomes
Low risk8 women excluded after randomisation (5.3%).

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said 'randomised' but no other information.
Withdrawals: 4 (12%), 1 exp (changed her mind), 3 control (2 severe hypertension, 1 breathlessness).


Participants33 women 12-24 weeks' gestation with SBP 140-170 mmHg and DBP 90-110 mmHg x 2, 24 hr apart.
Excluded: if 'usual' contraindications to beta blockers.


InterventionsExp: atenolol 50-200 mg/day.
Control: placebo (character not stated).


OutcomesWomen: mean BP, severe hypertension, stopped drug due to side-effects.
Babies: stillbirth, birthweight, SGA (< 5th centile), placental weight, gestation at delivery (mean).


NotesKorotkoff phase V used for DBP. The trial was stopped early when the principal investigator left Glasgow. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomised, placebo-controlled, double blind study...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blind, placebo-controlled trial.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskYes.

Incomplete outcome data (attrition bias)
All outcomes
High risk4 withdrawals (12.1%).

Selective reporting (reporting bias)Low riskAdditional data provided by authors.

Other biasUnclear risk.


MethodsAllocation concealment: numbered, sealed opaque envelopes. Stratified by parity.


Participants114 women with singleton pregnancy at 24-39 weeks' gestation with DBP > 90 mmHg for > 24 hr and no proteinuria.
Excluded: psychoneurosis, cardiac abnormality, diabetes, asthma, contraindication to beta blockers, antenatal antihypertensive treatment.


InterventionsExp: labetalol 100 mg x 2/day, increased up to 400 mg x 3/day.
Control: no antihypertensive.


OutcomesWomen: proteinuria (> 1+ or 0.25 g/L), duration of stay in hospital (mean), side-effects, changed drug due to side-effects, elective delivery, caesarean section.
Babies: perinatal death, gestation at delivery (mean), preterm delivery (< 37 weeks), SGA (<5th centile), admission to SCBU, length of stay in hospital (mean).


NotesKorotkoff phase IV used for DBP. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Low riskNumbered, sealed opaque envelopes. Stratified by parity.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Low riskAdditional data provided by authors.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: not stated. Authors said 'allocated randomly to treatment or no treatment'.


Participants58 women with hypertension before pregnancy or BP >/= 140/90 mmHg x 2 more than 24 hr apart before 20 weeks' gestation. Excluded: DBP > 100 mmHg, nulliparous, other major medical or obstetric problem.


InterventionsExp: methyldopa 750-2000 mg/day, hydrochlorothiazide 50 mg/day, hydralazine 75-250 mg/day.
Control: no antihypertensive.


OutcomesWomen: severe hypertension, proteinuria (> 1+ or > 300 mg/L in 24 hr), caesarean section.
Babies: perinatal death, gestation at delivery, birthweight < 2500 g, fetal distress, SGA (undefined).


NotesNo information about how BP measured. In exp group, 11 women had methyldopa + hydrochlorothiazide, 10 hydralazine + hydrochlorothiazide, 8 had all 3 drugs.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...allocated randomly to treatment or no treatment...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: physician drew a sealed envelope containing assignment.
Withdrawals: 14 women (7%), 8 exp and 6 control refused hospitalisation, but data reported for perinatal death.


Participants200 primigravid women in hospital at 26-35 weeks' gestation with SBP 140-160 mmHg and DBP 90-110 mmHg, proteinuria > 0.3 g/L and uric acid > 4.6 mg/dL.
Excluded: associated medical and obstetrical complications, other antihypertensive medication.


InterventionsExp: hospitalisation + labetalol 300 mg/day, increased every few days to max 2400 mg/day.
Control: hospitalisation alone.


OutcomesWomen: severe hypertension, increased proteinuria, eclampsia, placental abruption, caesarean section, renal function, days gained during management.
Babies: perinatal death, gestation at delivery (mean), birthweight (mean), placental weight, admission to SCBU, SGA (< 10th centile).


NotesNo mention of how BP measured.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated list of random numbers.

Allocation concealment (selection bias)Low riskSealed envelopes.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low risk14 withdrawals (7%). 8 in treatment group and 6 in control group refused hospitalisation, but data reported for perinatal death.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: not stated. Authors said 'randomly allocated', no further information.


Participants25 women at < 34 weeks' gestation, singleton pregnancy with BP 140/90 mmHg x 2 at least 6 hr apart and no proteinuria. Presumed chronic hypertension.


InterventionsExp: methyldopa 750 mg x 3/day to 2000 mg x 4/day.
Control: placebo, in the same way.
If severe pre-eclampsia, hydralazine or MgSO4 added.


OutcomesWomen: MAP, new proteinuria (2+ or greater on urine dipsticks), PE (defined as a sudden rise of 30 mmHg SBP or 15 mmHg DBP and weight gain > 2 lbs/week, or proteinuria > 2+), elective delivery, side-effects.
Babies: perinatal death, gestation at delivery (mean), birthweight (mean and < 50th centile).


NotesNo information about how BP measured.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described.

Allocation concealment (selection bias)Unclear riskNot described: "...randomly allocated...". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble blind, placebo controlled.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskYes.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.


MethodsAllocation concealment: envelope randomisation, using computer-generated random numbers. 3-arm study.
Withdrawals: 37 women (12%). 27 exp (21 excluded due to poor compliance, 3 twin, 1 abortion and 2 lost to follow-up) and 10 control (8 due to poor compliance, 1 twin and 1 spontaneous abortion).


Participants300 women in antenatal ward with chronic mild-moderate hypertension at 6-13 weeks' gestation. All had chronic hypertension before pregnancy and no associated medical complications.


InterventionsExp: (1) methyldopa 750-4000 mg/day (no other details). (2) labetalol 300-2400 mg/day (no other details).
Control: no antihypertensive.


OutcomesWomen: PE (defined as hypertension, proteinuria, and hyperuricaemia), additional antihypertensive, days in hospital, placental abruption, congestive heart failure, serum creatinine, uric acid.
Babies: perinatal death, gestation at delivery, birthweight < 2.5 kg, preterm delivery (< 37 weeks), SGA (undefined), admission to SCBU, hypoglycaemia, 5 min Apgar < 7.


NotesKorotkoff phase IV used for DBP. 36% of women were taking an antihypertensive at the time of trial entry. Additional data provided by authors.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated list of random numbers.

Allocation concealment (selection bias)Low riskSealed envelopes (personal communication).

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
High riskWithdrawals: 37 women (12%). 27 exp (21 excluded due to poor compliance, 3 twin, 1 abortion and 2 lost to follow-up) and 10 control (8 due to poor compliance, 1 twin and 1 spontaneous abortion).

Selective reporting (reporting bias)Low riskAdditional data provided by authors.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: physician drew sealed envelope containing assignment. Computer-generated random numbers.
Withdrawals: 3 women (1.5%) lost to follow-up (2 exp, 1 control).


Participants200 primigravid women at 26-36 weeks' gestation with SBP 140-160 mmHg and/or DBP 90-110 mmHg 24 hr after hospitalisation, proteinuria > 300 mg/24 hr, and/or uric acid > 6 mg/dL.
Excluded: associated medical or obstetric complications, or fetal compromise (suspected abnormal fetal growth by US, abnormal fetal testing).


InterventionsExp: nifedipine 40-120 mg/day.
Control: bed rest alone.


OutcomesWomen: MAP, severe proteinuria (> 5 g/24 hr), antenatal hospital stay (mean), days gained during management, caesarean section, placental abruption, HELLP syndrome.
Babies: stillbirth, neonatal death, birthweight, preterm delivery (< 37 weeks), SGA (< 10th centile), admission to SCBU, days in SCBU (mean).


NotesMethod of measuring blood pressure not mentioned.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated list of random numbers.

Allocation concealment (selection bias)Low riskSealed envelopes.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low risk3 women lost to follow-up (1.5%). 2 in treatment group and 1 in control group.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasLow riskGroups appear comparable at baseline.


MethodsAllocation concealment: not stated. Treatment assigned using random-number tables.


Participants31 women > 14 weeks' gestation with either chronic hypertension or mild-moderate PIH (BP 140-169/90-109 mmHg x 2 after 5 min rest).
Excluded: contraindication to beta blockers, Rh or haemorrhagic disorders.


InterventionsExp: mepindolol 5 mg/day, increased weekly to 10 mg/day.
Control: methyldopa 250 mg x 2/day increased weekly to 250 mg x 4/day.


OutcomesWomen: severe hypertension, caesarean section, induction of labour.
Babies: perinatal death, gestation at delivery, birthweight, Apgar score.


NotesMain paper in Spanish.
Method of measuring blood pressure not mentioned.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom-number table.

Allocation concealment (selection bias)Unclear riskNot described: [Estudio prospectivo randomizado] "randomised, prospective trial". No further details.

Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen label trial.

Blinding of outcome assessment (detection bias)
All outcomes
High riskNo.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo.

Selective reporting (reporting bias)Unclear riskAssessment from published study report.

Other biasUnclear risk.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Argentina 1990Most women with severe chronic hypertension. Women with mild-moderate HT not analysed separately.

Methods: open, prospective, randomised, comparative 3-arm trial.

Participants: 90 women with severe chronic hypertension.

Intervention: Atenolol (50-200 mg daily), vs methyldopa (500-2000 mg daily) vs ketanserin (80-120 mg daily).

Outcomes: BP, gestational age at delivery, birthweight, 1-min Apgar score, fetal and neonatal mortality.

Argentina 1994Not clearly randomised. Available as abstract only.
Methods: 'divided into two groups'. No further information.
Participants: 187 women with chronic hypertension (n = 66) or gestational hypertension (n = 121).
Interventions: atenolol 40-100 mg/day versus methyldopa 250-2000 mg/day.
Outcomes: superimposed pre-eclampsia, maternal BP, birthweight.

Australia 1985aComparison of 2 alpha agonists.
Methods: 'prospective, double blinded'. Women entered in a numerical sequence. No numbers missed or used a second time.
Participants: 100 women with BP > 130/85 mmHg or a rise of 30/15 mmHg from previous values.
Intervention: clonidine 150-1200 mcg/day versus methyldopa 250-2000 mg/day. If additional treatment needed, hydralazine.
Outcomes: severe hypertension, need for additional drug, stopped treatment due to side-effects, stillbirth, neonatal death, preterm delivery, birthweight (mean), SGA, 5-min Apgar.

Australia 1991Entry criteria was DBP greater than 1 SD above the reported mean for gestational age. Mean BP of recruited women was 129/84 mmHg at entry to the trial (122-136/79-89 mmHg) for the placebo group, and 126/82 mmHg (118-134/79-85) for the treatment group.
Participants: 52 nulliparous with singleton pregnancies between 28 and 34 weeks of gestation, without proteinuria.
Intervention: clonidine from 200 to 800 mcg a day plus hydralazine from 50 to 200 mg a day, and placebo.
Outcomes: severe hypertension, imminent eclampsia, eclampsia, severe proteinuria, antepartum haemorrhage, HELLP syndrome, fetal distress, fetal death, IUGR.

Belgium 1988Comparison of 2 beta blockers. Available as abstract only.
Methods: 'randomised', no further information.
Participants: 23 women with BP at least 140/90 mmHg x 2 and no proteinuria.
Intervention: atenolol 100 mg a day vs pindolol 15 mg a day.
Outcomes: umbilical PI, maternal BP, birthweight, Apgar score.

Brazil 1997Single-dose intervention. No clinical outcomes studied (effect of nifedipine in placental blood flow). Article in Portuguese. Only abstract translated into English.
Methods: double blind, placebo-controlled, RCT.
Participants: 65 women with pre-eclampsia.
Intervention: nifedipine 20 mg orally (only dose) vs placebo.
Outcomes: placental blood flow prior and 30 minutes after the intervention.

Brazil 2000Quasi-random design. Main paper in Portuguese.
Methods: alternated allocation (data extracted from original thesis). 11 women (10.5%) excluded after trial entry.
Participants: 105 women with singleton pregnancies diagnosed with pre-eclampsia, chronic hypertension, and pre-eclampsia superimposed to chronic hypertension.
Intervention: isradipine (slow release), 5 mg every 12 hr vs atenolol 50 mg every 12 hr.
Outcomes: BP, maternal heart rate, proteinuria, maternal side-effects, mode of delivery, gestational age, birthweight, SGA babies, Apgar score.

Brazil 2000b40 women (24%) excluded after randomisation. Reasons for exclusion were: missed appointment for Doppler (70%), non-compliance (20%), side-effects (7.5%), preterm delivery (2.5%). Data were not presented by treatment arm. Main paper in Portuguese.
Methods: randomised, double-blind, placebo-controlled trial.
Participants: 123 pregnant women with chronic hypertension.
Intervention: verapamil 240 mg/day vs placebo during 30 days.
Outcomes: Doppler PI, RI and S/D ratio, incidence of pre-eclampsia, birthweight, gestational age at delivery, SGA.

China 1991Herbal medicine vs magnesium sulphate. No clinical data available. Article in Chinese. Only abstract translated into English.
Methods: not reported. Authors said: '...randomly designed to...'.
Participants: 75 women with 'hypertension syndrome of pregnancy'.
Intervention: Magnesium sulphate 20-25 g/day vs ligustrazine 120-160 mg/day.
Outcomes: MAP, proteinuria, haematocrit, side-effects, positive rate of NST, Apgar score.

China 1993Only dose intervention. Sublingual nifedipine previous to caesarean section. Article in Chinese. Only abstract translated into English.
Methods: not reported. Indexed as publication type: RCT.
Participants: 33 women with pre-eclampsia undergoing emergent caesarean section.
Intervention: sublingual nifedipine, 16 mg (only dose). Control group not reported in abstract.
Outcomes: MAP, systolic and diastolic BP, maternal heart rate, postoperative haematocrit, side-effects.

China 1998Single-dose intervention. No clinical outcomes studied (effect of nimodipine in retinal blood flow). Article in Chinese. Only abstract translated into English.
Methods: not stated. Indexed as publication type: RCT.
Participants: 28 women with PIH.
Intervention: nimodipine 30 mg orally (only dose) vs IV magnesium sulphate.
Outcomes: retinal PI.

China 1999Herbal medicine + nifedipine vs nifedipine. No clinical outcomes studied. Article in Chinese. Only abstract translated into English.
Methods: not stated. Indexed as publication type: RCT.
Participants: 95 women with PIH.
Intervention: prepared rhubarb + nifedipine vs nifedipine.
Outcomes: serum lipids, and other blood tests.

China 2000Less than 7 days treatment. Treatment was given only during labour. Article in Chinese. Only abstract translated into English.
Methods: "64 cases of PIH were randomly divided into...".
Participants: 64 women with PIH.
Interventions: Nifedipine orally given every 6 hrs during labour vs no treatment.
Outcomes: postpartum haemorrhage.

Cuba 1994Quasi-random design. Article in Spanish.
Methods: alternate allocation (data provided by author).
Participants: 90 pregnant women with chronic hypertension.
Intervention: methyldopa (1-2 g/day) or hydralazine (100-200 mg/day) vs no treatment.
Outcomes: BP, superimposed pre-eclampsia, abruption, preterm delivery, LBW, Apgar score, RDS, hypoxia, fetal death.

Czech Republic 1993Comparison of 2 beta blockers. Article in Czech. Only abstract translated into English.
Methods: 'divided at random'. No further information.
Participants: 40 women with DBP 95-105 mmHg.
Intervention: atenolol 50-100 mg/day versus bisoprolol 5-10 mg/day.
Outcomes: BP, maternal heart rate, side-effects.

Denmark 1991Intervention is not an antihypertensive: magnesium vs placebo.
Methods: "...patients were allocated in a double-blind and randomised manner, based in a computer-generated list of numbers...".
Participants: 61 women with PIH. Chronic HT excluded. Withdrawals: 3 women (2 from intervention group, 1 from control group) excluded after randomisation.
Intervention: 48-hr of either IV magnesium or placebo infusion followed by daily oral magnesium or placebo tablets.
Outcomes: MAP, caesarean section, induction of labour, side-effects, gestational age, birthweight, Apgar score, admission to SCBU and days of stay.

Denmark 2000Intervention is not an antihypertensive: magnesium vs methyldopa.
Methods: RCT. Allocation concealment by numbered sealed opaque envelopes.
Participants: 33 women with PIH. Chronic HT excluded.
Intervention: magnesium, 48-hr IV infusion followed by daily oral magnesium vs methyldopa 250 mg x 4/day.
Outcomes: BP, gestational age, birthweight, admission to SCBU and length of stay, serum magnesium.

Dominican Rep 1992Not a RCT. Article in Spanish. Only abstract translated into English.
Methods: not stated. Authors only says "...divided into 2 groups...". Women known as given the drugs under study were also included.
Participants: 50 pregnant women with chronic HT + superimposed pre-eclampsia.
Intervention: slow-release nifedipine 20 mg every 8 hr vs methyldopa 500 mg every 12 hr.
Outcomes: BP, Apgar score.

Dominican Rep 1992aNot a RCT. Article in Spanish. Only abstract translated into English.
Methods: not stated. Authors only says "...divided into 2 groups...".
Participants: 30 pregnant women with severe pre-eclampsia.
Intervention: methyldopa 250-500 mg every 5 hr vs hydralazine 20-50 mg every 8 hr.
Outcomes: BP, maternal side-effects.

Egypt 1988No relevant clinical outcomes reported. Available as abstract only.
Methods: 'patients were randomly allocated to three treatment groups'. No further information.
Participants: 50 primigravidae with pre-eclamptic toxaemia and 20 multigravidae with essential hypertension in their late pregnancy.
Interventions: 3-arm trial: bromocriptine 5 mg, methyldopa 1 gr, and placebo, in different combinations. No further information.
Outcomes: serum prolactin and serum placental lactogen, BP. 1-year follow-up reported.

Egypt 1993One-week intervention. Outcomes measured at 30 min, 3 and 7 days.
Methods: 'randomly allocated' .
Participants: 30 women with PE in the third trimester. 25 women had mild PE with DBP 100-109 mmHg and 5 had severe PE with DBP >/= 110 mmHg.
Intervention: nifedipine 20 mg every 8 hr for 7 days or placebo in the same time and duration.
Outcomes: BP and fetal heart rate measured at 30 min, 3 and 7 days. Renal function tests and Doppler scans of umbilical cord.

Egypt 1997The intervention is not an antihypertensive. Naltrexone vs placebo. Available as an abstract only.
Methods: "...were randomly allocated to either naltrexone (...) or placebo".
Participants: 20 women with PIH at 30-36 weeks' gestation.
Intervention: naltrexone (opioid receptor antagonist), 50 mg every 12 hr vs placebo.
Outcomes: BP, proteinuria, oedema, prolactin levels, gestational age, status of the baby at birth.

Egypt 2009The intervention is not an antihypertensive. Ozone therapy (rectal insufflations).
Methods: "...were randomly assigned into two groups in equal numbers as follow...".
Participants: 30 hypertensive pregnant women at 24 weeks' gestation.
Intervention: ozone therapy by rectal Insufflations 3 sessions/week for 7 weeks + methyldopa vs methyldopa.
Outcomes: BP, resistance and pulsatility index, dose of methyldopa required.

Finland 1988Comparison of 2 beta blockers.
Methods: 'according to randomisation table'. No further information.
Participants: 51 women with BP > 149/94 mmHg x 2 in sitting position after 2 days bed rest in hospital.
Intervention: atenolol 50-100 mg/day versus pindolol 10-20 mg/day. If needed, hydralazine 150 mg/day added.
Outcomes: stillbirths, side-effects, need for additional drug, caesarean section, gestation at delivery (mean), birthweight (mean), 5 min Apgar.

Finland 1988aNo relevant clinical outcomes reported, report of ongoing study. Available as abstract only.
Methods: 'randomised pilot trial'. No further information.
Participants: 25 women with PIH.
Interventions: nifedipine 30-60 mg a day versus no treatment.
Outcomes: mean DBP, birthweight (mean).

Finland 1995Comparison of 2 beta blockers. Less than 7 days treatment, single-dose study. Women with mild hypertension not reported separately from severe hypertension.
Methods: 'randomly chosen'. No further information.
Participants: 24 women with a singleton pregnancy at 28-40 weeks, and either mild or severe pre-eclampsia (BP > 160/110 mmHg plus proteinuria > 5 g/24 hr, or BP 140/90-160/110 mmHg plus proteinuria < 5 g/24 hr).
Intervention: atenolol 0.15 mg/kg IV vs pindolol 0.006 mg/kg IV in 100 mL of Ringer's solution. Infusion time 15-20 min.
Outcomes: utero and umbilicoplacental vascular impedance, fetal haemodynamics and cardiac function.

Finland 1999Main outcomes were assessed only at 5-7 days of inclusion. 29% of women were excluded from the analysis.
Methods: randomised, double-blind, double-dummy study.
Participants: 24 women with singleton pregnancies between 29 and 39 weeks with BP > 140/90 mmHg x2, 6 hr apart, and proteinuria > 0.3 g in 24 hr urine collection.
Intervention: isradipine 2.5 mg twice daily or placebo vs metoprolol 50 mg twice daily or placebo (double-dummy study).
Outcomes: insulin sensitivity, uric acid, degree of proteinuria, lipids and lipoproteins, BP, umbilical artery RI, birthweight, placental weight, caesarean section, Apgar scores.

France 1988aNo clinical outcomes reported. Outcomes assessed at 4 weeks after trial entry. Available as abstract only.
Methods: 'randomised' no further information. 3-arm study.
Participants: 29 women with isolated hypertension after 'a mean period of 18 weeks of pregnancy'.
Intervention: pindolol vs atenolol versus methyldopa.
Outcomes: BP, maternal heart rate, serum sodium, potasium, uric acid, creatinine, plasma renin activity and aldosterone.

France 1990No clinical data reported. Available as congress abstracts only (1 in English, 3 in French).
Methods: 'randomised protocol'.
Participants: 21 women with moderate hypertension (SBP 140-180 mmHg and DBP 90-120 mmHg).
Intervention: oral atenolol (n = 12) vs nifedipine (n = 9) (no doses reported).
Outcomes: BP, Doppler measures, birthweight and length, Apgar score, admission to SCBU.

Germany 2012Not mild-moderate HT. Prevention study.

Methods: randomised, placebo-controlled, double blind study.

Participants: 111 pregnant women with abnormal placental perfusion at 19 - 24 weeks' gestation.

Intervention: NO-donor penterythriltetranitrat (n = 54) vs placebo (n = 57).

Outcomes: utero-placental perfusion, preterm birth, IUGR, pre-eclampsia, fetal deaths.

Hong Kong 1993No clinical data available. Abstract report.
Methods: allocated in 'randomised double manner'. No further information. 4 women (6.2%) excluded after randomisation.
Participants: 65 primigravid women with a singleton pregnancy at > 20 weeks' gestation and BP 140-165/90-105 mmHg x 2, 6 hr apart but no proteinuria.
Interventions: labetalol (dose not reported) vs placebo (vitamin C).
Outcomes: BP, need for additional antihypertensives, induction of labour, proteinuria, gestational age, mode of delivery, birthweight, Apgar score.

Hungary 199928% of women excluded after randomisation (7 because of treatment duration not exceeding 10 days and 2 dropped out).
Methods: allocation 'according to randomisation list'. No further information.
Participants: 32 healthy primigravidae with BP at least 140/90 mmHg x 2 at least 6 hr apart.
Interventions: calcium dobesilate 2 g a day vs placebo.
Outcomes: new proteinuria, caesarean section, placental abruption, preterm delivery.

India 1999Intervention is an antiplatelet agent. Available as abstract only.
Methods: randomised, placebo-controlled trial.
Participants: 163 women with PIH of 20-32 weeks' gestation.
Intervention: aspirin 60 mg a day vs placebo from 22 until 38 weeks of gestation.
Outcomes: prevention of PIH grade B (BP 160/110 mmHg x 2, 4 hr apart), proteinuria 2+ or more, perinatal mortality, maternal mortality, eclampsia, SGA (< 10th centile).

India 2011Not possible to extract data. Available as abstract only.

Methods: prospective randomised comparative study.

Participants: 200 women with singleton pregnancy, 28-40 weeks' gestation with pregnancy-induced hypertension.

Intervention: oral labetalol versus oral methyldopa.

Outcomes: BP, control of proteinuria, mode of delivery, neonatal Apgar score, NICU admission, neonatal complications, perinatal deaths.

India 2012aIncludes women with severe hypertension. IV labetalol given to this subgroup, not analysed separately.

Methods: prospective, randomised controlled parallel group study.

Participants: 90 women with singleton, vertex pregnancies at 20-40 weeks' gestation with BP >/= 140/90, with and without proteinuria.

Intervention: oral or IV Labetalol versus oral methyldopa.

Outcomes: serum urea and creatinine, significant proteinuria, severe maternal complications, induction of labour, caesarean section, lactation, gestational age at delivery, Apgar score, admission to NICU, RDS, bradycardia, jaundice, hypoglycaemia.

India 2012bIntervention is not an antihypertensive: magnesium sulphate vs placebo. No clinical outcomes studied. 27% women (18/66) excluded after randomisation.
Methods: women were randomly allocated by sealed envelopes containing computer-generated random numbers. Double-blind, placebo-controlled.
Participants: 66 women with mild pre-eclampsia or PIH after 34 weeks' gestation.
Intervention: 24-hr of either IV magnesium sulphate or placebo infusion.
Outcomes: umbilical artery and fetal middle cerebral artery pulsatility index.

Iran 2000Quasi-random design (data from personal communication). Available as abstract only.
Methods: 'patients were sequentially assigned to one of two randomised groups'. Alternate allocation (data obtained from personal communication).
Participants: 37 pregnant women over 26 weeks' gestation with blood pressure over 140/90 mmHg (after 24-48 hr resting) + proteinuria or generalised oedema.
Intervention: nifedipine 10 mg t.i.d. vs hydralazine 10 mg t.i.d.
Outcomes: BP, termination of pregnancy, side-effects.

Iran 2005Intervention is not an antihypertensive: IV magnesium sulphate vs oral magnesium chloride. No clinical outcomes studied.
Methods: randomised controlled open clinical trial.
Participants: 68 women with mild pre-eclampsia.
Intervention: IV magnesium sulphate (2 g/h) or oral magnesium chloride (4 g/2h).
Outcomes: serum Mg levels at 3, 6 and 12 hr after administration.

Israel 1988Comparison of 2 beta blockers. Published as abstract only.
Methods: 'allocated in blind and randomised manner'. No further information.
Participants: 30 women with SBP 140-170 mmHg and DBP 90-110 mmHg x 2, 6 hr apart.
Intervention: Atenolol 100 mg plus 2 placebo tablets vs pindolol 5 mg x 3/day.
Outcomes: gestation at delivery (mean).

Israel 1992aComparison of 2 beta blockers.
Methods: 'randomly allocated to double blind treatment'. No further information.
Participants: 20 women with mild PE, BP >/= 140/90 mmHg.
Interventions: propranolol 40 mg x 3/day vs pindolol 5 mg x 3/day, for 7 days.
Outcomes: BP, umbilical artery Doppler.

Israel 1999Single-dose intervention.
Methods: double-blind, placebo-controlled RCT.
Participants: 23 women with PIH.
Intervention: sublingual tablet of Isosorbide dinitrate (5 mg) or placebo (single dose).
Outcomes: maternal BP and heart rate, umbilical artery Doppler.

Italy 1986Not an RCT (matched controls). Available as abstract only.
Methods: 'randomised protocol', no further information, for group A (nifedipine or atenolol), control group (B) was matched by age and parity with group A. Results in group A were not presented separately.
Participants: 10 women with mild-moderate hypertension in the third trimester (group A).
Interventions: atenolol 100 mg a day or slow-release nifedipine 20 mg x 2/day (group A) vs diuretics or bed rest (group B).
Outcomes: BP, gestational age, birthweight, Apgar score, serum bilirubin, preterm delivery, RDS, side-effects.

Italy 1990Quasi-randomised design. 2 trials with same methods reported in 1 paper (1) 44 women (2) 50 women.
Methods: allocation by 'order of attendance at clinic or department'.
Participants: women with BP =/> 140/90 mmHg x 2 over 8 hr, normal BP before pregnancy.
Intervention: (1) slow-release verapamil 360-480 mcg/day vs pindolol 15-20 mg/day. (2) slow-release verapamil 360-480 mcg/day vs atenolol 100-150 mg/day.
Outcomes: caesarean section, baby death, Apgar (mean), gestation at delivery (mean).

Italy 1990aIntervention is an antiplatelet agent. No clinical outcomes reported. Available as abstract only.
Methods: '...using a random selection...'. No further information.
Participants: 20 women with PIH before 36 weeks' gestation.
Intervention: picotamide (no dose reported) vs no treatment.
Outcomes: platelet aggregation, ADP-threshold values, collagen concentration thresholds.

Italy 2000aWomen had chronic hypertension or history of hypertension or IUGR (results were not presented separately).
Methods: "...patients were randomly allocated to two treatments...".
Participants: 68 women with either chronic hypertension or with previous history of PE or IUGR.
Intervention: glyceryl trinitrate transdermal patch (5 mg/24 hr) for 14-16 hr/day from 16 to 38 weeks' gestation vs observation.
Outcomes: hypertensive syndrome, preterm delivery, abruptio, birthweight, IUGR, Apgar score, admission to SCBU, RDS, neonatal death, umbilical and cerebral artery PI.

Italy 2001Not clearly randomised. No clinical data reported. Available as congress abstract only.
Methods: not stated.
Participants: 24 women with PIH.
Intervention: isosorbide dinitrate sublingual every 6 hr (n = 12) vs nifedipine 20 mg daily (n = 12).
Outcomes: apoptosis in placental tissues.

Italy 2004Intervention is not an antihypertensive: acupuncture + methyldopa vs. methyldopa. Protocol for a future RCT. Available as abstract only.

Methods: planned RCT

Participants: 60 women with chronic hypertension at 16-20 weeks' gestation.

Intervention: acupuncture + methyldopa vs. methyldopa.

Outcomes:need for antihypertensives.

Italy 2006Intervention is not an antihypertensive. Single-dose treatment.
Methods: double-blind, randomised, cross-over design.
Participants: 15 pregnant women at 30-34 weeks' gestation with mild/moderate PIH.
Intervention: L-Arginine 20 g /500 mL vs placebo infusion.
Outcomes: systolic and diastolic BP, fetal heart rate and fetal movements.

Italy 2008Intervention is not an antihypertensive. Available only as an abstract.
Methods: double-blind, randomised, placebo-controlled trial.
Participants: 20 pregnant women with pre-eclampsia.
Intervention: L-Arginine 1.66g 3 times a day vs placebo.
Outcomes: Serum L-arginine levels, adverse maternal and fetal outcomes.

Italy 2010Intervention is not an antihypertensive.
Methods: double-blind, randomised, placebo-controlled trial.
Participants: 80 pregnant women with mid chronic hypertension.
Intervention: L-Arginine vs placebo.
Outcomes: BP, need for additional antihypertensives, superimposed pre-eclampsia, adverse maternal and fetal outcomes.

Japan 1997Single-dose intervention. No clinical outcomes studied.
Methods: "...randomly allocated into two groups using sealed envelopes...".
Participants: 18 pregnant women with SBP = or > 140 mmHg and DBP = or > 90 mmHg, with or without proteinuria and oedema.
Intervention: isosorbide dinitrate patches (40 mg, only dose) and bed rest vs bed rest alone.
Outcomes: systolic and diastolic BP, uterine and umbilical Doppler velocimetry.

Kuwait 1995Not clearly randomised.
Methods: 'randomly allocated in sequence'. No further information.
Participants: 120 primigravid women > 26 weeks' gestation, with SBP 120-140 mmHg and DBP 95-105 mmHg persisting for 3 days.
Intervention: labetalol 100-300 mg x 3/day vs methyldopa 250-750 mg x 3/day.
Outcomes: maternal MAP, proteinuria (undefined), placental abruption, caesarean section, elective delivery, side-effects, 1 min Apgar score < 5, days on SCBU, birthweight (mean).

Mexico 2008Intervention is not an antihypertensive. Available only as an abstract.

Methods: randomised, placebo-controlled trial.

Participants: 100 pregnant women with pre-eclampsia.

Intervention: L-Arginine vs placebo.

Outcomes: birthweight, SGA babies.

Pakistan 1994Intervention is an antiplatelet agent.
Methods: 'randomly divided into two groups'. No further information.
Participants: 200 women, 1 group with previous history of PIH (100 women) and other with mild essential hypertension or those developing BP 140/90 mmHg x 2 at least 15 days apart (100 women).
Intervention: aspirin 75 mg b.i.d. vs routine antihypertensive treatment with beta blockers or calcium channel blockers when DBP exceeded 100 mmHg.
Outcomes: development of PE. No other relevant outcomes reported.

Panama 2012Severe hypertension. Ongoing trial.

Methods: randomised, open label trial.

Participants: 284 (estimated) women with at > 24 weeks' gestation with severe HT (SBP > 160 mmHg/DBP > 110 mmHg).

Intervention: 5 mg IV hydralazine every 15 min until BP controlled vs. IV labetalol ant increasing doses until BP controlled.

Outcomes: BP control.

Philippines 20003 days treatment. No relevant clinical outcomes studied. Available as abstract only.
Methods: randomised, double-blind, placebo-controlled trial.
Participants: 16 pre-eclamptics (no further details).
Intervention: nitrol patch 5 mg for 16 hr for 3 consecutive days vs the same regimen using a gauze only.
Outcomes: uterine and umbilical Doppler velocimetry.

Russia 1993Possibly not a RCT. Full text awaiting translation from Russian. Abstract only in English.
Participants: 92 women with slight and medium-severe hypertension at 24-39 weeks' gestation.
Interventions: venodilators, prazosin and cordafen are all mentioned. Not clear how the groups were constructed.

Singapore 1996More than 20% of women excluded, 6 women (22%) excluded because delivered in the week after trial entry.
Methods: 'by opening a sealed envelope'.
Participants: 27 women with singleton pregnancies, DBP 90 mmHg or above and proteinuria.
Interventions: isradipine (slow release) 5 mg a day vs methyldopa 750 mg a day.
Outcomes: MAP, side-effects, caesarean section, perinatal mortality, birthweight, admission to SCBU, Apgar score, maternal and fetal haemodynamics (by Doppler).

Singapore 1998No relevant clinical outcomes studied.
Methods: 'randomised', no further information.
Participants: 30 women with PE, DBP >/= 90 mmHg and proteinuria >/= 300 mg/24 hr.
Interventions: methyldopa 250-500 mg x 3/day vs isradipine 5-10 mg once/day.
Outcomes: haemostatic parameters only (thrombelastography, fibrinogen, antithrombin III, thrombin-antithrombin-complex, beta-thromboglobulin, plasminogen activators, plasminogen activators inhibitors, and plasminogen).

Slovakia 2002Not a RCT.

Methods: cohort study.

Participants: women with hypertension during pregnancy.

Interventions: acebutolol vs other antihypertensives.

Outcomes: maternal and perinatal adverse events.

South Africa 1988Quasi-random design. Less than 7 days treatment, single-dose study. No clinical outcomes reported.
Methods: quasi-random design, using last digit of the hospital number.
Participants: 18 women in the last trimester of pregnancy with hypertension +/- proteinuria.
Interventions: nifedipine 5 mg vs placebo (single dose).
Outcomes: measures of uteroplacental blood flow.

South Africa 1990Included women with severe hypertension (DBP 100-120 mmHg).
Methods: 'randomly allocated', no further information.
Participants: 60 women at 28-36 weeks' gestation with mean 24 hr DBP 100-120 mmHg +/- proteinuria.
Intervention: indoramin 50 mg twice daily vs methyldopa 1 g twice daily vs placebo 1 tablet daily.
Outcomes: MAP, need for additional antihypertensive.

South Africa 1991aQuasi-random design. Single-dose intervention.
Methods: allocation 'by virtue of the last digit of their folder number'.
Participants: 19 women at > 28 weeks' gestation, singleton pregnancy and hypertension (defined as mean DBP >/= 90 mmHg).
Intervention: sublingual nifedipine 5 mg vs placebo (single dose).
Outcomes: DBP (mean), maternal and fetal heart rate, gestational age, side-effects.

South Africa 1997Most women did not have hypertension. Eligibility criteria DBP >/= 80 mmHg, before 20 weeks' gestation. Of 138 recruited women, less than half had DBP >/= 90 mmHg. Results for this group were not presented separately.
Methods: sequentially-numbered sealed boxes containing drug or placebo.
Participants: 138 women between 12-20 weeks' gestation with DBP 80-109 mmHg, without antihypertensive therapy.
Intervention: ketanserin 40-80 mg a day vs placebo.
Outcomes: severe HT, proteinuria, placental abruption, other drugs needed, perinatal deaths, SGA (< 10th centile), birthweight.

Spain 1988No clinical outcomes reported. Number of women in each group not reported. Available as abstract only.
Methods: 'double-blind, placebo-controlled trial', no further information.
Participants: 31 women with mild hypertension (BP 140-160/90 110 mmHg) despite bed rest in hospital.
Intervention: labetalol 200-600 mg a day vs placebo.
Outcomes: severe HT, need for additional antihypertensives, MAP, caesarean section, perinatal deaths, fetal distress.

Sri Lanka 1994Quasi-random design.
Methods: 'patients were alternately allocated'.
Participants: 126 women with PIH.
Interventions: nifedipine 30-90 mg/day vs methyldopa 750-2000 mg/day.
Outcomes: severe hypertension, gestation at delivery (mean), birthweight (mean).

Sweden 1992Comparison of 2 beta blockers.
Methods: 'randomly allocated' using 'double-blind dummy technique'. No further information.
Participants: 32 women admitted to hospital with PIH in the third trimester (BP >/= 140/90 mmHg x 2 at least 4 hr apart) and normotensive in the first trimester.
Intervention: atenolol 50 mg x 2/day vs pindolol 5 mg x 2/day, for at least 1 week.
Outcomes: side-effects, caesarean section, maternal haemodynamics, fetal haemodynamics, admission to SCBU, birthweight (mean), 5 min Apgar score.

Sweden 1993It is not clear from papers whether reported data represent only a subgroup of women.
Methods: not stated. Authors said 'allocated at random'.
Participants: 20 women at 26-37 weeks' gestation with 'persistent' DBP >/= 100 mmHg and proteinuria.
Intervention: labetalol 300-1000 mg/day orally (if necessary, IV 25 mg bolus followed by 25-65 mg/hr infusion), vs hydralazine 75-400 mg/day orally (if necessary, 1.5-6.0 mg/hr infusion).
Outcomes: severe hypertension, additional antihypertensive, caesarean section, neonatal death, birthweight (mean), gestation at delivery (mean), SGA (2 SD below mean), bradycardia, hypotension, hypoglycaemia, 5 min Apgar < 7, RDS, cord pH (< 7.20).

Uganda 1992Status unknown.

Personal communication of a planned RCT of aspirin and methyldopa in moderate hypertension during pregnancy. No further data.

UK 1978Included women with severe hypertension.
Methods: 'randomly allocated'. No further information.
Participants: 74 women with singleton pregnancy with DBP >or = to 170/100 mm Hg x 2 at up to 36 weeks' gestation.
Intervention: labetalol 100 mg (max 1200 mg daily) vs methyldopa 250 mg (up to 4000 mg daily).
Outcomes: severe hypertension, proteinuria ('greater than trace'), additional antihypertensive therapy, changed drugs due to maternal side-effects, caesarean section, perinatal mortality, SGA infants (< 10th centile), intubated, umbilical cord pH.

UK 1991Less than 7 days treatment, single-dose study.
Methods: sequentially-numbered, sealed envelopes.
Participants: 30 women with singleton pregnancy and hypertension, defined as BP >/= 140/90 mmHg.
Intervention: 10 mg hydralazine IV vs or 100 mg labetalol IV, as single dose.
Outcomes: MAP, maternal and fetal heart rate, side-effects, umbilical artery PI.

USA 1957Not randomised. Although a group of women received placebo, results are presented together with a group of matched controls. Included women with severe hypertension.
Methods: not stated.
Participants: 106 pregnant women with chronic hypertension and 28 women with severe pre-eclampsia. In addition 671 women with chronic hypertension were included as controls.
Intervention: oral reserpine 0.25 to 3 mg/day (n = 80) vs placebo (n = 26). 28 women received IV reserpine.
Outcomes: status at birth, birthweight.

USA 1981Study included 63 women, but only 21 randomised. Outcomes not reported separately for randomised women.
Methods: 'randomly and blindly assigned'. No further information.
Participants: 21 women with BP 140/90 mmHg or above in a seated position or at rest, x 2, 6 or more hr apart.
Intervention: hydralazine 25 mg x 3/day vs methyldopa 250 mg x 3/day vs placebo x 3/day.
Outcomes: MAP, caesarean section, induction of labour, birthweight.

USA 1990aStatus unknown.

Personal communication of a planned RCT of oral hypotensive agents in early onset pre-eclampsia. No further data.

USA 1991Not a randomised trial. No clinical outcomes reported.
Methods: placebo group were matched as controls.
Participants: 16 women at 17-22 weeks' gestation.
Intervention: 10 mg sublingual nifedipine vs placebo.
Outcomes: S/D ratio of the uterine artery, maternal BP, maternal heart rate.

USA 2005Intervention is not an antihypertensive. Ongoing trial.

Methods: randomised controlled trial. Sequentially numbered opaque envelopes.

Participants: 50 pregnant women with chronic hypertension.

Intervention: target blood pressure of 120-130/80-85 mmHg vs target blood pressure 140-150/90-100 mmHg.

Outcomes: BP, superimposed pre-eclampsia, worsening hypertension, HELLP syndrome, gestational age, birthweight, serious perinatal complications.

Venezuela 1985Not randomised. Included women with severe hypertension. Article in Spanish.
Methods: alternated allocation (personal communication).
Participants: 32 pregnant women at > 25 weeks' gestation with severe pre-eclampsia (defined as BP 160/110 or 140/90) and symptoms as headache, epigastric pain, blurred vision or hyperreflexia.
Intervention: labetalol 200-800 mg/day vs methyldopa 750-2000 mg/day.
Outcomes: maternal MAP, maternal pulse rate, gestational age at delivery, birthweight, 1 min Apgar, fetal and neonatal death.

Venezuela 1997Not a RCT. Matched controls. Article in Spanish.
Methods: controls were women treated with methyldopa in the same study period, with the same characteristics than the study group.
Participants: 20 women with PIH.
Intervention: labetalol 200 to 300 mg orally given every 12 hr vs methyldopa from 500 to 1500 mg/day
Outcomes: BP, severe hypertension, gestational age, induction of labour, caesarean section, birthweight.

Venezuela 2001No relevant clinical outcomes reported. Less than 7 days of treatment. Available as abstract only.
Methods: Authors said '...were randomly assigned to...'. No further information.
Participants: 30 pre-eclamptic. No further information.
Intervention: transdermal nitroglycerin (7 mg for 12 hr for 2 consecutive days) vs placebo.
Outcomes: umbilical S/D ratio, PI and RI by Doppler ultrasound.

Venezuela 2007Mixed control group. Available only as an abstract.

Method: "...were randomly assigned to two study groups...".

Participants: 30 women with pre-eclampsia-eclampsia and gestational hypertension.

Intervention: Carvedilol vs traditional antihypertensive drugs (methyldopa and/or nifedipine).

Outcomes: BP control, additional antihypertensives, maternal and fetal complications, Apgar score, fetal heart rate.

 
Characteristics of studies awaiting assessment [ordered by study ID]

MethodsRandomised, multicentre, blinded, placebo-controlled trial.

ParticipantsTreatment arm: all women who have been diagnosed with pre-eclampsia, are being followed clinically and who provide informed consent. For a diagnosis of pre-eclampsia a patient must meet all 3 criteria:

1. Systolic blood pressure greater than 140 mmHg or an increase of 30 mmHg from the participant’s baseline (with that increase present at 2 measurements taken 6 hours apart).

2. Diastolic blood pressure greater than 90 mmHg or an increase of 15 mmHg from the participant’s baseline (with that increase present at 2 measurements taken 6 hours apart).

3. Proteinuria greater than 0.3 g in 24 hour urine or 2+ on dipstick.

InterventionsTreatment arm: experimental intervention: daily dose of low-dose Isosorbide-5-mononitrate (ISMN) (30 mg) following diagnosis of pre-eclampsia after 24 weeks' gestation till delivery.

Control intervention: matching placebo containing lactose. Patients randomly assigned to either receive low dose ISMN (30 mg) as stated above or placebo.

OutcomesPrimary outcome: randomisation-to-delivery interval between ISMN/placebo groups, measured at delivery. Secondary outcomes: serial change in biochemical markers in treatment/no treatment groups, measured at routine obstetrical visits until delivery (generally every 2 weeks), incidence of any side-effects (major or minor), measured at routine obstetrical visits until delivery (generally every 2 weeks), neonatal outcomes (composite of neonatal morbidity), measured at delivery.

NotesOngoing trial. Author contacted.

 
Comparison 1. Any antihypertensive drug versus none (subgrouped by class of drug)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Maternal death5525Risk Ratio (M-H, Fixed, 95% CI)1.08 [0.24, 4.83]

 2 Eclampsia5578Risk Ratio (M-H, Fixed, 95% CI)0.34 [0.01, 8.15]

 3 Severe hypertension202558Risk Ratio (M-H, Fixed, 95% CI)0.49 [0.40, 0.60]

   3.1 Beta blocker versus none
8762Risk Ratio (M-H, Fixed, 95% CI)0.38 [0.26, 0.57]

   3.2 Beta blocker + other drug versus none
2322Risk Ratio (M-H, Fixed, 95% CI)0.30 [0.12, 0.77]

   3.3 Methyldopa versus none
2310Risk Ratio (M-H, Fixed, 95% CI)0.32 [0.17, 0.58]

   3.4 Methyldopa + other drug versus none
158Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.12, 3.70]

   3.5 Beta blocker or methyldopa versus none
2412Risk Ratio (M-H, Fixed, 95% CI)0.43 [0.25, 0.74]

   3.6 Calcium channel blocker versus none
4662Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.60, 1.11]

   3.7 Alpha blocker versus none
132Risk Ratio (M-H, Fixed, 95% CI)0.07 [0.00, 1.09]

 4 Proteinuria/pre-eclampsia232851Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.80, 1.08]

   4.1 Beta blocker versus none
8883Risk Ratio (M-H, Fixed, 95% CI)0.73 [0.57, 0.94]

   4.2 Beta blocker + other drug versus none
2322Risk Ratio (M-H, Fixed, 95% CI)1.26 [0.63, 2.51]

   4.3 Methyldopa versus none
2267Risk Ratio (M-H, Fixed, 95% CI)1.22 [0.55, 2.71]

   4.4 Methyldopa + other drug versus none
2158Risk Ratio (M-H, Fixed, 95% CI)0.74 [0.43, 1.30]

   4.5 Beta blocker or methyldopa versus none
2412Risk Ratio (M-H, Fixed, 95% CI)0.77 [0.50, 1.19]

   4.6 Calcium channel blocker versus none
4725Risk Ratio (M-H, Fixed, 95% CI)1.40 [1.06, 1.86]

   4.7 Alpha blocker versus none
132Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.04, 2.52]

   4.8 Glyceryl trinitrate versus none
116Risk Ratio (M-H, Fixed, 95% CI)0.43 [0.06, 3.28]

   4.9 Regular antihypertensive therapy versus none
136Risk Ratio (M-H, Fixed, 95% CI)0.19 [0.02, 1.39]

 5 Severe pre-eclampsia3416Risk Ratio (M-H, Fixed, 95% CI)0.54 [0.24, 1.23]

 6 HELLP syndrome1197Risk Ratio (M-H, Fixed, 95% CI)2.02 [0.38, 10.78]

   6.1 Calcium channel blocker versus none
1197Risk Ratio (M-H, Fixed, 95% CI)2.02 [0.38, 10.78]

 7 Pulmonary oedema2325Risk Ratio (M-H, Fixed, 95% CI)1.24 [0.30, 5.12]

   7.1 Beta blocker versus none
1176Risk Ratio (M-H, Fixed, 95% CI)5.23 [0.25, 107.39]

   7.2 Beta blocker or methyldopa versus none
1149Risk Ratio (M-H, Fixed, 95% CI)0.51 [0.07, 3.48]

 8 Additional antihypertensive101285Risk Ratio (M-H, Fixed, 95% CI)0.42 [0.30, 0.58]

   8.1 Beta blocker versus none
3245Risk Ratio (M-H, Fixed, 95% CI)0.40 [0.23, 0.70]

   8.2 Beta blocker + other drug versus none
2315Risk Ratio (M-H, Fixed, 95% CI)0.32 [0.13, 0.82]

   8.3 Methyldopa + other drug versus none
158Risk Ratio (M-H, Fixed, 95% CI)0.31 [0.11, 0.83]

   8.4 Beta blocker or methyldopa versus none
1263Risk Ratio (M-H, Fixed, 95% CI)0.52 [0.22, 1.20]

   8.5 Calcium channel blocker versus none
2372Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.35, 1.28]

   8.6 Alpha blocker versus none
132Risk Ratio (M-H, Fixed, 95% CI)0.07 [0.00, 1.09]

 9 Changed/stopped drugs due to maternal side-effects151403Risk Ratio (M-H, Fixed, 95% CI)2.59 [1.33, 5.04]

   9.1 Beta blocker versus none
9745Risk Ratio (M-H, Fixed, 95% CI)1.90 [0.76, 4.75]

   9.2 Beta blocker + other drug versus none
2315Risk Ratio (M-H, Fixed, 95% CI)1.30 [0.30, 5.61]

   9.3 Methyldopa versus none
125Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

   9.4 Calcium channel blocker versus none
2302Risk Ratio (M-H, Fixed, 95% CI)4.10 [0.46, 36.21]

   9.5 Glyceryl trinitrate versus none
116Risk Ratio (M-H, Fixed, 95% CI)18.75 [1.25, 281.11]

 10 Maternal side-effects11934Risk Ratio (M-H, Fixed, 95% CI)1.53 [1.10, 2.12]

   10.1 Beta blocker versus none
7554Risk Ratio (M-H, Fixed, 95% CI)2.07 [1.21, 3.54]

   10.2 Beta blocker + other drug versus none
1154Risk Ratio (M-H, Fixed, 95% CI)1.30 [0.30, 5.61]

   10.3 Methyldopa versus none
125Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

   10.4 Calcium channel blocker versus none
1185Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.60, 1.52]

   10.5 Glyceryl trinitrate versus none
116Risk Ratio (M-H, Fixed, 95% CI)18.75 [1.25, 281.11]

 11 Antenatal hospital admission4455Risk Ratio (M-H, Fixed, 95% CI)0.87 [0.73, 1.03]

   11.1 Beta blocker versus none
152Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.57, 1.24]

   11.2 Beta blocker + other drug versus none
2254Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.78, 1.17]

   11.3 Beta blocker or methyldopa versus none
1149Risk Ratio (M-H, Fixed, 95% CI)0.51 [0.26, 0.98]

 12 Induction of labour5563Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.77, 1.07]

   12.1 Beta blocker versus none
3384Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.83, 1.16]

   12.2 Beta blocker + other drug versus none
1154Risk Ratio (M-H, Fixed, 95% CI)0.49 [0.26, 0.90]

   12.3 Methyldopa versus none
125Risk Ratio (M-H, Fixed, 95% CI)1.54 [0.46, 5.09]

 13 Elective delivery (induction of labour + elective caesarean section)4710Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.83, 1.00]

   13.1 Beta blocker versus none
2240Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.84, 1.13]

   13.2 Beta blocker + other drug versus none
3470Risk Ratio (M-H, Fixed, 95% CI)0.87 [0.77, 0.99]

 14 Caesarean section202624Risk Ratio (M-H, Fixed, 95% CI)0.92 [0.83, 1.02]

   14.1 Beta blocker versus none
8850Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.86, 1.30]

   14.2 Beta blocker + other drug versus none
2322Risk Ratio (M-H, Fixed, 95% CI)0.57 [0.38, 0.84]

   14.3 Methyldopa versus none
2272Risk Ratio (M-H, Fixed, 95% CI)0.86 [0.57, 1.30]

   14.4 Methyldopa + other drug versus none
158Risk Ratio (M-H, Fixed, 95% CI)1.8 [0.69, 4.72]

   14.5 Beta blocker or methyldopa versus none
2412Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.67, 1.19]

   14.6 Calcium channel blocker versus none
3642Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.83, 1.09]

   14.7 Alpha blocker versus none
132Risk Ratio (M-H, Fixed, 95% CI)0.63 [0.20, 1.91]

   14.8 Regular antihypertensive therapy versus none
136Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 15 Placental abruption111433Risk Ratio (M-H, Fixed, 95% CI)1.41 [0.65, 3.07]

   15.1 Beta blocker versus none
3364Risk Ratio (M-H, Fixed, 95% CI)5.11 [0.25, 104.96]

   15.2 Beta blocker + other drug versus none
2322Risk Ratio (M-H, Fixed, 95% CI)2.24 [0.34, 14.98]

   15.3 Methyldopa versus none
170Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

   15.4 Beta blocker or methyldopa versus none
2412Risk Ratio (M-H, Fixed, 95% CI)0.52 [0.13, 2.03]

   15.5 Calcium blocker versus none
1197Risk Ratio (M-H, Fixed, 95% CI)1.52 [0.26, 8.87]

   15.6 Alpha blocker versus none
132Risk Ratio (M-H, Fixed, 95% CI)3.33 [0.34, 32.96]

   15.7 Regular antihypertensive therapy versus none
136Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 16 Total reported fetal or neonatal death (including miscarriage)273230Risk Ratio (M-H, Fixed, 95% CI)0.71 [0.49, 1.02]

   16.1 Beta blocker versus none
111045Risk Ratio (M-H, Fixed, 95% CI)1.02 [0.46, 2.29]

   16.2 Beta blocker + other drug versus none
2322Risk Ratio (M-H, Fixed, 95% CI)1.21 [0.33, 4.43]

   16.3 Methyldopa versus none
3337Risk Ratio (M-H, Fixed, 95% CI)0.35 [0.13, 0.94]

   16.4 Methyldopa + other drug versus none
2158Risk Ratio (M-H, Fixed, 95% CI)0.58 [0.23, 1.44]

   16.5 Beta blocker or methyldopa versus none
2443Risk Ratio (M-H, Fixed, 95% CI)0.58 [0.22, 1.55]

   16.6 Calcium channel blocker versus none
5857Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.28, 2.05]

   16.7 Alpha blocker versus none
132Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.25, 2.73]

   16.8 Regular antihypertensive therapy versus none
136Risk Ratio (M-H, Fixed, 95% CI)2.24 [0.22, 22.51]

 17 Fetal or neonatal death (subgrouped by time of death)25Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

   17.1 Miscarriage
71058Risk Ratio (M-H, Fixed, 95% CI)0.39 [0.17, 0.93]

   17.2 Stillbirth
182480Risk Ratio (M-H, Fixed, 95% CI)1.14 [0.60, 2.17]

   17.3 Perinatal death
202382Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.60, 1.54]

   17.4 Neonatal death
4557Risk Ratio (M-H, Fixed, 95% CI)0.79 [0.14, 4.34]

 18 Preterm birth (< 37 weeks)152141Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.85, 1.10]

   18.1 Beta blocker versus none
4361Risk Ratio (M-H, Fixed, 95% CI)0.90 [0.62, 1.32]

   18.2 Beta blocker + other drug versus none
2322Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.63, 1.46]

   18.3 Methyldopa versus none
2272Risk Ratio (M-H, Fixed, 95% CI)1.61 [0.73, 3.58]

   18.4 Beta blocker or methyldopa versus none
2412Risk Ratio (M-H, Fixed, 95% CI)0.66 [0.42, 1.05]

   18.5 Calcium channel blocker versus none
4742Risk Ratio (M-H, Fixed, 95% CI)1.03 [0.88, 1.21]

   18.6 Alpha blocker versus none
132Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.27, 1.66]

 19 Preterm birth (subgrouped by gestational age)15Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

   19.1 < 37 weeks
101569Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.85, 1.13]

   19.2 < 36 weeks
2304Risk Ratio (M-H, Fixed, 95% CI)0.77 [0.37, 1.59]

   19.3 < 34 weeks
5792Risk Ratio (M-H, Fixed, 95% CI)1.19 [0.77, 1.83]

   19.4 Unspecified
4423Risk Ratio (M-H, Fixed, 95% CI)1.26 [0.87, 1.82]

 20 Small-for-gestational age202586Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.80, 1.17]

   20.1 Beta blocker versus none
9904Risk Ratio (M-H, Fixed, 95% CI)1.38 [0.99, 1.92]

   20.2 Beta blocker + other drug versus none
2322Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.46, 2.02]

   20.3 Methyldopa versus none
2227Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.26, 3.70]

   20.4 Methyl dopa + other drug versus none
158Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.28, 3.62]

   20.5 Beta blocker or methyldopa versus none
2412Risk Ratio (M-H, Fixed, 95% CI)0.66 [0.43, 1.01]

   20.6 Calcium channel blocker versus none
3640Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.60, 1.16]

   20.7 Alpha blocker versus none
123Risk Ratio (M-H, Fixed, 95% CI)0.43 [0.05, 3.57]

 21 Small-for-gestational age (subgrouped by severity)19Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

   21.1 Birthweight < 10th centile
101265Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.79, 1.24]

   21.2 Birthweight < 5th centile
3287Risk Ratio (M-H, Fixed, 95% CI)3.04 [1.25, 7.40]

   21.3 Unspecified
71090Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.51, 1.10]

 22 Admission to special care baby unit91470Risk Ratio (M-H, Random, 95% CI)1.04 [0.83, 1.30]

   22.1 Beta blocker versus none
3449Risk Ratio (M-H, Random, 95% CI)1.07 [0.82, 1.41]

   22.2 Beta blocker + other drug versus none
1151Risk Ratio (M-H, Random, 95% CI)0.66 [0.38, 1.14]

   22.3 Methyldopa versus none
2272Risk Ratio (M-H, Random, 95% CI)1.56 [0.88, 2.78]

   22.4 Beta blocker or methyldopa versus none
1149Risk Ratio (M-H, Random, 95% CI)0.51 [0.27, 0.95]

   22.5 Calcium channel blocker versus none
2449Risk Ratio (M-H, Random, 95% CI)1.18 [0.87, 1.62]

 23 Respiratory distress syndrome5825Risk Ratio (M-H, Fixed, 95% CI)0.28 [0.12, 0.63]

   23.1 Beta blocker versus none
3412Risk Ratio (M-H, Fixed, 95% CI)0.28 [0.11, 0.71]

   23.2 Beta blocker + other drug versus none
1157Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.03, 3.10]

   23.3 Calcium channel blocker versus none
1256Risk Ratio (M-H, Fixed, 95% CI)0.20 [0.01, 4.06]

 24 Neonatal hypoglycaemia5862Risk Ratio (M-H, Fixed, 95% CI)0.77 [0.51, 1.17]

   24.1 Beta blocker versus none
2261Risk Ratio (M-H, Fixed, 95% CI)0.73 [0.24, 2.24]

   24.2 Beta blocker + other drug versus none
1157Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.35, 1.84]

   24.3 Beta blocker or methyldopa versus none
1261Risk Ratio (M-H, Fixed, 95% CI)2.07 [0.23, 18.24]

   24.4 Calcium channel blocker versus none
1183Risk Ratio (M-H, Fixed, 95% CI)0.69 [0.39, 1.21]

 25 Neonatal bradycardia3418Risk Ratio (M-H, Fixed, 95% CI)1.93 [1.05, 3.53]

   25.1 Beta blocker versus none
2261Risk Ratio (M-H, Fixed, 95% CI)2.61 [1.32, 5.15]

   25.2 Beta blocker + other drug versus none
1157Risk Ratio (M-H, Fixed, 95% CI)0.25 [0.03, 2.16]

 26 Neonatal jaundice3529Risk Ratio (M-H, Fixed, 95% CI)0.78 [0.56, 1.09]

   26.1 Beta blocker versus none
1144Risk Ratio (M-H, Fixed, 95% CI)0.53 [0.19, 1.47]

   26.2 Methyldopa versus none
1202Risk Ratio (M-H, Fixed, 95% CI)1.02 [0.65, 1.61]

   26.3 Calcium channel blocker versus none
1183Risk Ratio (M-H, Fixed, 95% CI)0.62 [0.35, 1.10]

 27 Follow-up of the children at 1 year: cerebral palsy1110Risk Ratio (M-H, Fixed, 95% CI)0.33 [0.01, 8.01]

 28 Follow-up of the children at 7 1/2 years1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

   28.1 Chronic ill health
1190Risk Ratio (M-H, Fixed, 95% CI)0.70 [0.16, 3.06]

   28.2 Impaired hearing
1190Risk Ratio (M-H, Fixed, 95% CI)1.10 [0.38, 3.14]

   28.3 Impaired vision
1190Risk Ratio (M-H, Fixed, 95% CI)0.47 [0.20, 1.11]

 
Comparison 2. Any antihypertensive drug versus none (subgrouped by type of hypertensive disorder at trial entry)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Severe hypertension202558Risk Ratio (M-H, Fixed, 95% CI)0.49 [0.40, 0.60]

   1.1 Hypertension alone
4493Risk Ratio (M-H, Fixed, 95% CI)0.27 [0.15, 0.47]

   1.2 Hypertension + proteinuria
2256Risk Ratio (M-H, Fixed, 95% CI)0.26 [0.13, 0.54]

   1.3 Chronic hypertension
4538Risk Ratio (M-H, Fixed, 95% CI)0.57 [0.34, 0.98]

   1.4 Unclassified/mixed
101271Risk Ratio (M-H, Fixed, 95% CI)0.60 [0.47, 0.77]

 2 Proteinuria/pre-eclampsia232851Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.80, 1.08]

   2.1 Hypertension alone
8684Risk Ratio (M-H, Fixed, 95% CI)0.72 [0.57, 0.92]

   2.2 Hypertension + proteinuria
2383Risk Ratio (M-H, Fixed, 95% CI)1.65 [0.92, 2.97]

   2.3 Chronic hypertension
4605Risk Ratio (M-H, Fixed, 95% CI)0.92 [0.66, 1.28]

   2.4 Unclassified/mixed
91179Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.80, 1.36]

 3 Total reported fetal or neonatal death (including miscarriage)273230Risk Ratio (M-H, Fixed, 95% CI)0.71 [0.49, 1.02]

   3.1 Hypertension alone
7668Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.42, 1.65]

   3.2 Hypertension + proteinuria
3475Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.30, 2.59]

   3.3 Chronic hypertension
5665Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.40, 2.21]

   3.4 Unclassified/mixed
121422Risk Ratio (M-H, Fixed, 95% CI)0.55 [0.31, 0.96]

 4 Preterm birth (< 37 weeks)152141Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.85, 1.10]

   4.1 Hypertension alone
5607Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.56, 1.00]

   4.2 Hypertension + proteinuria
2267Risk Ratio (M-H, Fixed, 95% CI)1.24 [0.92, 1.67]

   4.3 Chronic hypertension
2447Risk Ratio (M-H, Fixed, 95% CI)1.15 [0.72, 1.86]

   4.4 Unclassified/mixed
6820Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.80, 1.15]

 5 Small-for-gestational age202586Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.80, 1.17]

   5.1 Hypertension alone
6623Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.57, 1.24]

   5.2 Hypertension + proteinuria
2391Risk Ratio (M-H, Fixed, 95% CI)1.54 [0.93, 2.54]

   5.3 Chronic hypertension
5628Risk Ratio (M-H, Fixed, 95% CI)0.80 [0.53, 1.23]

   5.4 Unclassified/mixed
7944Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.71, 1.30]

 
Comparison 3. Any antihypertensive drug versus none (subgrouped by gestation at trial entry)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Severe hypertension202558Risk Ratio (M-H, Fixed, 95% CI)0.49 [0.40, 0.60]

   1.1 Entry < 32 weeks
71071Risk Ratio (M-H, Fixed, 95% CI)0.63 [0.47, 0.83]

   1.2 Entry > 32 weeks
1120Risk Ratio (M-H, Fixed, 95% CI)0.29 [0.06, 1.32]

   1.3 Unclassified/mixed
121367Risk Ratio (M-H, Fixed, 95% CI)0.40 [0.30, 0.53]

 2 Proteinuria/pre-eclampsia232851Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.80, 1.08]

   2.1 Entry < 32 weeks
81147Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.81, 1.36]

   2.2 Entry > 32 weeks
2120Risk Ratio (M-H, Fixed, 95% CI)0.34 [0.12, 0.96]

   2.3 Unclassified/mixed
131584Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.75, 1.10]

 3 Total reported fetal or neonatal death (including miscarriage)273230Risk Ratio (M-H, Fixed, 95% CI)0.71 [0.49, 1.02]

   3.1 Entry < 32 weeks
101276Risk Ratio (M-H, Fixed, 95% CI)0.66 [0.39, 1.14]

   3.2 Entry > 32 weeks
1120Risk Ratio (M-H, Fixed, 95% CI)0.5 [0.05, 5.37]

   3.3 Unclassified/mixed
161834Risk Ratio (M-H, Fixed, 95% CI)0.77 [0.47, 1.27]

 4 Preterm birth (< 37 weeks)152141Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.85, 1.10]

   4.1 Entry < 32 weeks
6993Risk Ratio (M-H, Fixed, 95% CI)0.99 [0.82, 1.20]

   4.2 Entry > 32 weeks
00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

   4.3 Unclassified/mixed
91148Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.79, 1.13]

 5 Small-for-gestational age202586Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.80, 1.17]

   5.1 Entry < 32 weeks
101185Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.63, 1.11]

   5.2 Entry > 32 weeks
1117Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.46, 2.67]

   5.3 Unclassified/mixed
91284Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.83, 1.43]

 
Comparison 4. Any antihypertensive drug versus none (subgrouped by use of placebo)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Severe hypertension202558Risk Ratio (M-H, Fixed, 95% CI)0.49 [0.40, 0.60]

   1.1 Placebo
10937Risk Ratio (M-H, Fixed, 95% CI)0.50 [0.36, 0.69]

   1.2 No placebo
101621Risk Ratio (M-H, Fixed, 95% CI)0.48 [0.38, 0.62]

 2 Proteinuria/pre-eclampsia232851Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.80, 1.08]

   2.1 Placebo
10869Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.71, 1.09]

   2.2 No placebo
131982Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.78, 1.20]

 3 Total reported fetal or neonatal death (including miscarriage)273230Risk Ratio (M-H, Fixed, 95% CI)0.71 [0.49, 1.02]

   3.1 Placebo
10911Risk Ratio (M-H, Fixed, 95% CI)0.79 [0.37, 1.69]

   3.2 No placebo
172319Risk Ratio (M-H, Fixed, 95% CI)0.69 [0.46, 1.04]

 4 Preterm birth (< 37 weeks)152141Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.85, 1.10]

   4.1 Placebo
5566Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.62, 1.17]

   4.2 No placebo
101575Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.86, 1.15]

 5 Small-for-gestational age202586Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.80, 1.17]

   5.1 Placebo
8714Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.64, 1.38]

   5.2 No placebo
121872Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.78, 1.22]

 
Comparison 5. Any antihypertensive versus methyldopa (subgrouped by class of drug)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Severe hypertension11638Risk Ratio (M-H, Random, 95% CI)0.54 [0.30, 0.95]

   1.1 Beta blocker versus methyldopa
9592Risk Ratio (M-H, Random, 95% CI)0.59 [0.33, 1.05]

   1.2 Calcium channel blockers versus methyldopa
246Risk Ratio (M-H, Random, 95% CI)0.23 [0.04, 1.22]

 2 Proteinuria/pre-eclampsia11997Risk Ratio (M-H, Fixed, 95% CI)0.73 [0.54, 0.99]

   2.1 Beta blocker versus methyldopa
10903Risk Ratio (M-H, Fixed, 95% CI)0.75 [0.53, 1.05]

   2.2 Calcium channel blockers versus methyldopa
194Risk Ratio (M-H, Fixed, 95% CI)0.66 [0.34, 1.27]

 3 Additional antihypertensive12989Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.66, 1.06]

   3.1 Beta blocker versus methyldopa
10853Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.69, 1.13]

   3.2 Calcium channel blocker versus methyldopa
2136Risk Ratio (M-H, Fixed, 95% CI)0.59 [0.29, 1.22]

 4 Antenatal hospital admission2275Risk Ratio (M-H, Fixed, 95% CI)0.77 [0.58, 1.03]

   4.1 Beta blocker versus methyldopa
2275Risk Ratio (M-H, Fixed, 95% CI)0.77 [0.58, 1.03]

 5 Elective delivery (induction of labour + elective caesarean section)5443Risk Ratio (M-H, Fixed, 95% CI)1.01 [0.86, 1.18]

   5.1 Beta blocker versus methyldopa
4333Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.84, 1.15]

   5.2 Calcium channel blocker versus methyldopa
1110Risk Ratio (M-H, Fixed, 95% CI)1.56 [0.59, 4.07]

 6 Caesarean section10878Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.78, 1.12]

   6.1 Beta blocker veresus methyldopa
9852Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.78, 1.13]

   6.2 Calcium channel blocker versus methyldopa
126Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.13, 3.35]

 7 Maternal side-effects6412Risk Ratio (M-H, Fixed, 95% CI)0.69 [0.52, 0.91]

   7.1 Beta blocker versus methyldopa
5302Risk Ratio (M-H, Fixed, 95% CI)0.69 [0.52, 0.91]

   7.2 Calcium channel blockers versus methyldopa
1110Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Changed/stopped drugs due to maternal side-effects4272Risk Ratio (M-H, Fixed, 95% CI)2.80 [0.12, 67.91]

   8.1 Beta blocker versus methyldopa
4272Risk Ratio (M-H, Fixed, 95% CI)2.80 [0.12, 67.91]

 9 Placental abruption1173Risk Ratio (M-H, Fixed, 95% CI)2.02 [0.19, 21.90]

   9.1 Beta blocker versus methyldopa
1173Risk Ratio (M-H, Fixed, 95% CI)2.02 [0.19, 21.90]

 10 Total reported fetal or neonatal death (including miscarriage)191339Risk Ratio (M-H, Fixed, 95% CI)0.73 [0.42, 1.27]

   10.1 Beta blocker versus methyldopa
151160Risk Ratio (M-H, Fixed, 95% CI)0.73 [0.40, 1.33]

   10.2 Calcium channel blocker versus methyldopa
3159Risk Ratio (M-H, Fixed, 95% CI)0.31 [0.04, 2.65]

   10.3 Ketanserin versus methyldopa
120Risk Ratio (M-H, Fixed, 95% CI)3.0 [0.14, 65.90]

 11 Preterm birth (< 37 weeks)9623Risk Ratio (M-H, Fixed, 95% CI)0.76 [0.55, 1.05]

   11.1 Beta blocker versus methyldopa
7574Risk Ratio (M-H, Fixed, 95% CI)0.81 [0.57, 1.15]

   11.2 Calcium channel blocker versus methyldopa
249Risk Ratio (M-H, Fixed, 95% CI)0.53 [0.24, 1.17]

 12 Small-for-gestational age7597Risk Ratio (M-H, Fixed, 95% CI)0.80 [0.53, 1.21]

   12.1 Beta blocker versus methyldopa
6577Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.55, 1.32]

   12.2 Calcium channel blocker versus methyldopa
120Risk Ratio (M-H, Fixed, 95% CI)0.4 [0.10, 1.60]

 13 Admission to special care baby unit4478Risk Ratio (M-H, Fixed, 95% CI)0.92 [0.67, 1.26]

   13.1 Beta blocker versus methyldopa
3453Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.66, 1.25]

   13.2 Calcium channel blocker versus methyldopa
125Risk Ratio (M-H, Fixed, 95% CI)1.27 [0.32, 5.12]

 14 Neonatal hypoglycaemia4321Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.50, 2.18]

   14.1 Beta blocker versus methyldopa
4321Risk Ratio (M-H, Fixed, 95% CI)1.05 [0.50, 2.18]

 15 Neonatal bradycardia128Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

   15.1 Beta blocker versus methyldopa
128Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 16 Neonatal jaundice128Risk Ratio (M-H, Fixed, 95% CI)1.2 [0.47, 3.03]

   16.1 Beta blocker versus methyldopa
128Risk Ratio (M-H, Fixed, 95% CI)1.2 [0.47, 3.03]

 
Comparison 6. Any antihypertensive versus calcium channel blocker (subgrouped by class of drug)

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Severe hypertension2136Risk Ratio (M-H, Fixed, 95% CI)2.09 [0.96, 4.57]

   1.1 Glyceryl trinitrate versus calcium channel blockers
136Risk Ratio (M-H, Fixed, 95% CI)1.56 [0.07, 35.67]

   1.2 Beta blockers versus calcium channel blockers
1100Risk Ratio (M-H, Fixed, 95% CI)2.14 [0.96, 4.80]

 2 Proteinuria/pre-eclampsia2128Risk Ratio (M-H, Fixed, 95% CI)2.15 [0.73, 6.38]

   2.1 Glyceryl trinitrate versus calcium channel blockers
136Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.10, 9.96]

   2.2 Beta blockers versus calcium channel blockers
192Risk Ratio (M-H, Fixed, 95% CI)2.67 [0.75, 9.42]

 3 HELLP syndrome1100Risk Ratio (M-H, Fixed, 95% CI)1.5 [0.26, 8.60]

   3.1 Beta blockers versus calcium channel blockers
1100Risk Ratio (M-H, Fixed, 95% CI)1.5 [0.26, 8.60]

 4 Additional antihypertensive1100Risk Ratio (M-H, Fixed, 95% CI)2.14 [0.96, 4.80]

   4.1 Beta blockers versus calcium channel blockers
1100Risk Ratio (M-H, Fixed, 95% CI)2.14 [0.96, 4.80]

 5 Changed/stopped drug due to side-effects2136Risk Ratio (M-H, Fixed, 95% CI)2.6 [0.13, 50.25]

   5.1 Glyceryl trinitrate versus calcium channel blockers
136Risk Ratio (M-H, Fixed, 95% CI)2.6 [0.13, 50.25]

   5.2 Beta blockers versus calcium channel blockers
1100Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Maternal side-effects1100Risk Ratio (M-H, Fixed, 95% CI)1.2 [0.39, 3.68]

   6.1 Beta blockers versus calcium channel blockers
1100Risk Ratio (M-H, Fixed, 95% CI)1.2 [0.39, 3.68]

 7 Elective delivery (induction of labour + elective caesarean section)1100Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.69, 1.15]

   7.1 Beta blockers versus calcium channel blockers
1100Risk Ratio (M-H, Fixed, 95% CI)0.89 [0.69, 1.15]

 8 Caesarean section1100Risk Ratio (M-H, Fixed, 95% CI)1.57 [0.91, 2.71]

   8.1 Beta blockers versus calcium channel blockers
1100Risk Ratio (M-H, Fixed, 95% CI)1.57 [0.91, 2.71]

 9 Placental abruption1100Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

   9.1 Beta blockers versus calcium channel blockers
1100Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 10 Total reported fetal or neonatal death (including miscarriage)2136Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.06, 15.55]

   10.1 Glyceryl trinitrate versus calcium channel blockers
136Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

   10.2 Beta blockers versus calcium channel blockers
1100Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.06, 15.55]

 11 Preterm birth (< 37 weeks)136Risk Ratio (M-H, Fixed, 95% CI)0.63 [0.20, 1.91]

   11.1 Glyceryl trinitrate versus calcium channel blockers
136Risk Ratio (M-H, Fixed, 95% CI)0.63 [0.20, 1.91]

 12 Small-for-gestational age136Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.10, 9.96]

   12.1 Glyceryl trinitrate versus calcium channel blockers
136Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.10, 9.96]

 13 Admission to special care baby unit199Risk Ratio (M-H, Fixed, 95% CI)1.47 [0.44, 4.89]

   13.1 Beta blockers versus calcium channel blockers
199Risk Ratio (M-H, Fixed, 95% CI)1.47 [0.44, 4.89]