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Meta-Analysis
. 2018 Oct 1;10(10):CD002252.
doi: 10.1002/14651858.CD002252.pub4.

Antihypertensive drug therapy for mild to moderate hypertension during pregnancy

Edgardo Abalos  1 , Lelia Duley, D Wilhelm Steyn, Celina Gialdini
Affiliations
Meta-Analysis

Antihypertensive drug therapy for mild to moderate hypertension during pregnancy

Edgardo Abalos et al. Cochrane Database Syst Rev. .

Abstract

Background: Antihypertensive drugs are often used in the belief that lowering blood pressure will prevent progression to more severe disease, and thereby improve pregnancy outcome. This Cochrane Review is an updated review, first published in 2001 and subsequently updated in 2007 and 2014.

Objectives: To assess the effects of antihypertensive drug treatments for women with mild to moderate hypertension during pregnancy.

Search methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (13 September 2017), and reference lists of retrieved studies.

Selection criteria: All randomised trials evaluating any antihypertensive drug treatment for mild to moderate hypertension during pregnancy, defined as systolic blood pressure 140 to 169 mmHg and/or diastolic blood pressure 90 to 109 mmHg. Comparisons were of one or more antihypertensive drug(s) with placebo, with no antihypertensive drug, or with another antihypertensive drug, and where treatment was planned to continue for at least seven days.

Data collection and analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy.

Main results: For this update, we included 63 trials (data from 58 trials, 5909 women), with moderate to high risk of bias overall.We carried out GRADE assessments for the main 'antihypertensive drug versus placebo/no antihypertensive drug' comparison only. Evidence was graded from very low to moderate certainty, with downgrading mainly due to design limitations and imprecision.For many outcomes, trials contributing data evaluated different hypertensive drugs; while we did not downgrade for this indirectness, results should be interpreted with caution.Antihypertensive drug versus placebo/no antihypertensive drug (31 trials, 3485 women)Primary outcomes: moderate-certainty evidence suggests that use of antihypertensive drug(s) probably halves the risk of developing severe hypertension (risk ratio (RR) 0.49; 95% confidence interval (CI) 0.40 to 0.60; 20 trials, 2558 women), but may have little or no effect on the risk of proteinuria/pre-eclampsia (average risk ratio (aRR) 0.92; 95% CI 0.75 to 1.14; 23 trials, 2851 women; low-certainty evidence). Moderate-certainty evidence also shows that antihypertensive drug(s) probably have little or no effect in the risk of total reported fetal or neonatal death (including miscarriage) (aRR 0.72; 95% CI 0.50 to 1.04; 29 trials, 3365 women), small-for-gestational-age babies (aRR 0.96; 95% CI 0.78 to 1.18; 21 trials, 2686 babies) or preterm birth less than 37 weeks (aRR 0.96; 95% CI 0.83 to 1.12; 15 trials, 2141 women).

Secondary outcomes: we are uncertain of the effect of antihypertensive drug(s) on the risk of maternal death, severe pre-eclampsia, or eclampsia, orimpaired long-term growth and development of the baby in infancy and childhood, because the certainty of this evidence is very low. There may be little or no effect on the risk of changed/stopped drugs due to maternal side-effects, or admission to neonatal or intensive care nursery (low-certainty evidence). There is probably little or no difference in the risk of elective delivery (moderate-certainty evidence).Antihypertensive drug versus another antihypertensive drug (29 trials, 2774 women)Primary outcomes: beta blockers and calcium channel blockers together in the meta-analysis appear to be more effective than methyldopa in avoiding an episode of severe hypertension (RR 0.70; 95% CI 0.56 to 0.88; 11 trials, 638 women). There was also an increase in this risk when other antihypertensive drugs were compared with calcium channel blockers (RR 1.86; 95% CI 1.09 to 3.15; 5 trials, 223 women), but no evidence of a difference when methyldopa and calcium channel blockers together were compared with beta blockers (RR1.18, 95% CI 0.95 to 1.48; 10 trials, 692 women). No evidence of a difference in the risk of proteinuria/pre-eclampsia was found when alternative drugs were compared with methyldopa (aRR 0.78; 95% CI 0.58 to 1.06; 11 trials, 997 women), with calcium channel blockers (aRR: 1.24, 95% CI 0.70 to 2.19; 5 trials, 375 women), or with beta blockers (aRR 1.21, 95% CI 0.88 to 1.67; 12 trials, 1107 women).For the babies, we found no evidence of a difference in the risk oftotal reported fetal or neonatal death (including miscarriage) when comparing other antihypertensive drugs with methyldopa (aRR 0.77, 95% CI 0.52 to 1.14; 22 trials, 1791 babies), with calcium channel blockers (aRR 0.90, 95% CI 0.52 to 1.57; nine trials, 700 babies), or with beta blockers (aRR: 1.23, 95% CI 0.81 to 1.88; 19 trials, 1652 babies); nor in the risk for small-for-gestational age in the comparison with methyldopa (aRR 0.79, 95% CI 0.52 to 1.20; seven trials, 597 babies), with calcium channel blockers (aRR 1.05, 95% CI 0.64 to 1.73; four trials, 200 babies), or with beta blockers (average RR 1.13, 95% CI 0.80 to 1.60; 7 trials, 680 babies). No evidence of an overall difference among groups in the risk of preterm birth (less than 37 weeks) was found in the comparison with methyldopa (aRR: 0.91; 95% CI 0.68 to 1.22; 11 trials, 835 women), with calcium channel blockers (aRR 0.85, 95% CI 0.59 to 1.23; six trials, 330 women), or with beta blockers (aRR 1.22, 95% CI 0.90 to 1.66; 9 trials, 806 women).

Secondary outcomes: There were no cases of maternal death andeclampsia. There is no evidence of a difference in the risk of severe pre-eclampsia, changed/stopped drug due to maternal side-effects, elective delivery, admission to neonatal or intensive care nursery when other antihypertensive drugs are compared with methyldopa, calcium channel blockers or beta blockers. Impaired long-term growth and development in infancy and childhood was not reported for these comparisons.

Authors' conclusions: Antihypertensive drug therapy for mild to moderate hypertension during pregnancy reduces the risk of severe hypertension. The effect on other clinically important outcomes remains unclear. If antihypertensive drugs are used, beta blockers and calcium channel blockers appear to be more effective than the alternatives for preventing severe hypertension. High-quality large sample-sized randomised controlled trials are required in order to provide reliable estimates of the benefits and adverse effects of antihypertensive treatment for mild to moderate hypertension for both mother and baby, as well as costs to the health services, women and their families.

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Conflict of interest statement

E Abalos: none known.

L Duley has been awarded an NIHR research grant for a programme of work on care at very preterm birth. She has no conflict of interest.

W Steyn is the author of one excluded trial (South Africa 1997). He has no other conflict of interest.

C Gialdini: none known.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
4
4
Funnel plot of comparison: 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), outcome: 1.1 Severe hypertension.
5
5
Funnel plot of comparison: 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), outcome: 1.2 Proteinuria/pre‐eclampsia.
6
6
Funnel plot of comparison: 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), outcome: 1.3 Total reported fetal or neonatal death (including miscarriage).
7
7
Funnel plot of comparison: 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), outcome: 1.5 Small‐for‐gestational age.
8
8
Funnel plot of comparison: 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), outcome: 1.7 Preterm birth (< 37 weeks).
9
9
Funnel plot of comparison: 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), outcome: 1.14 Need for additional antihypertensive drug/s.
10
10
Funnel plot of comparison: 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), outcome: 1.16 Caesarean section.
11
11
Funnel plot of comparison: 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), outcome: 1.19 Placental abruption.
12
12
Funnel plot of comparison: 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), outcome: 1.20 Maternal side‐effects.
13
13
Funnel plot of comparison: 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), outcome: 1.21 Changed/stopped drugs due to maternal side‐effects.
14
14
Funnel plot of comparison: 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), outcome: 1.22 Admission to neonatal or intensive care nursery.
15
15
Funnel plot of comparison: 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), outcome: 5.1 Severe hypertension.
16
16
Funnel plot of comparison: 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), outcome: 5.2 Proteinuria/pre‐eclampsia.
17
17
Funnel plot of comparison: 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), outcome: 5.3 Total reported fetal or neonatal death (including miscarriage).
18
18
Funnel plot of comparison: 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), outcome: 5.5 Preterm birth (< 37 weeks).
19
19
Funnel plot of comparison: 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), outcome: 5.8 Need for additional antihypertensive drug/s.
20
20
Funnel plot of comparison: 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), outcome: 5.10 Caesarean section.
21
21
Funnel plot of comparison: 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), outcome: 7.1 Severe hypertension.
22
22
Funnel plot of comparison: 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), outcome: 7.2 Proteinuria/pre‐eclampsia.
23
23
Funnel plot of comparison: 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), outcome: 7.3 Total reported fetal or neonatal death (including miscarriage).
24
24
Funnel plot of comparison: 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), outcome: 7.11 Need for additional antihypertensive drug/s.
25
25
Funnel plot of comparison: 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), outcome: 7.13 Caesarean section.
1.1
1.1. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 1 Severe hypertension.
1.2
1.2. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 2 Proteinuria/pre‐eclampsia.
1.3
1.3. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 3 Total reported fetal or neonatal death (including miscarriage).
1.4
1.4. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 4 Fetal or neonatal death (subgrouped by time of death).
1.5
1.5. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 5 Small‐for‐gestational age.
1.6
1.6. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 6 Small‐for‐gestational age (subgrouped by severity).
1.7
1.7. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 7 Preterm birth (< 37 weeks).
1.8
1.8. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 8 Preterm birth (subgrouped by gestational age).
1.9
1.9. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 9 Maternal death.
1.10
1.10. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 10 Severe pre‐eclampsia.
1.11
1.11. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 11 Eclampsia.
1.12
1.12. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 12 HELLP syndrome.
1.13
1.13. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 13 Pulmonary oedema.
1.14
1.14. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 14 Need for additional antihypertensive drug/s.
1.15
1.15. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 15 Elective delivery (induction of labour + elective caesarean section).
1.16
1.16. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 16 Caesarean section.
1.17
1.17. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 17 Induction of labour.
1.18
1.18. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 18 Antenatal hospital admission.
1.19
1.19. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 19 Placental abruption.
1.20
1.20. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 20 Maternal side‐effects.
1.21
1.21. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 21 Changed/stopped drugs due to maternal side‐effects.
1.22
1.22. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 22 Admission to neonatal or intensive care nursery.
1.23
1.23. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 23 Respiratory distress syndrome.
1.24
1.24. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 24 Neonatal hypoglycaemia.
1.25
1.25. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 25 Neonatal bradycardia.
1.26
1.26. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 26 Neonatal jaundice.
1.27
1.27. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 27 Follow‐up of the children at 1 year: cerebral palsy.
1.28
1.28. Analysis
Comparison 1 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by class of drug), Outcome 28 Follow‐up of the children at 7 1/2 years.
2.1
2.1. Analysis
Comparison 2 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by type of hypertensive disorder at trial entry), Outcome 1 Severe hypertension.
2.2
2.2. Analysis
Comparison 2 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by type of hypertensive disorder at trial entry), Outcome 2 Proteinuria/pre‐eclampsia.
2.3
2.3. Analysis
Comparison 2 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by type of hypertensive disorder at trial entry), Outcome 3 Total reported fetal or neonatal death (including miscarriage).
2.4
2.4. Analysis
Comparison 2 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by type of hypertensive disorder at trial entry), Outcome 4 Small‐for‐gestational age.
2.5
2.5. Analysis
Comparison 2 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by type of hypertensive disorder at trial entry), Outcome 5 Preterm birth (< 37 weeks).
3.1
3.1. Analysis
Comparison 3 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by gestation at trial entry), Outcome 1 Severe hypertension.
3.2
3.2. Analysis
Comparison 3 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by gestation at trial entry), Outcome 2 Proteinuria/pre‐eclampsia.
3.3
3.3. Analysis
Comparison 3 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by gestation at trial entry), Outcome 3 Total reported fetal or neonatal death (including miscarriage).
3.4
3.4. Analysis
Comparison 3 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by gestation at trial entry), Outcome 4 Small‐for‐gestational age.
3.5
3.5. Analysis
Comparison 3 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by gestation at trial entry), Outcome 5 Preterm birth (< 37 weeks).
4.1
4.1. Analysis
Comparison 4 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by use of placebo), Outcome 1 Severe hypertension.
4.2
4.2. Analysis
Comparison 4 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by use of placebo), Outcome 2 Proteinuria/pre‐eclampsia.
4.3
4.3. Analysis
Comparison 4 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by use of placebo), Outcome 3 Total reported fetal or neonatal death (including miscarriage).
4.4
4.4. Analysis
Comparison 4 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by use of placebo), Outcome 4 Small‐for‐gestational age.
4.5
4.5. Analysis
Comparison 4 Any antihypertensive drug versus no antihypertensive drugs/placebo (subgrouped by use of placebo), Outcome 5 Preterm birth (< 37 weeks).
5.1
5.1. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 1 Severe hypertension.
5.2
5.2. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 2 Proteinuria/pre‐eclampsia.
5.3
5.3. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 3 Total reported fetal or neonatal death (including miscarriage).
5.4
5.4. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 4 Small‐for‐gestational age.
5.5
5.5. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 5 Preterm birth (< 37 weeks).
5.6
5.6. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 6 Severe pre‐eclampsia.
5.7
5.7. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 7 Eclampsia.
5.8
5.8. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 8 Need for additional antihypertensive drug/s.
5.9
5.9. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 9 Elective delivery (induction of labour + elective caesarean section).
5.10
5.10. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 10 Caesarean section.
5.11
5.11. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 11 Induction of labour.
5.12
5.12. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 12 Antenatal hospital admission.
5.13
5.13. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 13 Placental abruption.
5.14
5.14. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 14 Maternal side‐effects.
5.15
5.15. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 15 Changed/stopped drugs due to maternal side‐effects.
5.16
5.16. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 16 Admission to neonatal or intensive care nursery.
5.17
5.17. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 17 Respiratory distress syndrome.
5.18
5.18. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 18 Neonatal hypoglycaemia.
5.19
5.19. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 19 Neonatal bradycardia.
5.20
5.20. Analysis
Comparison 5 Any antihypertensive versus methyldopa (subgrouped by class of drug), Outcome 20 Neonatal jaundice.
6.1
6.1. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 1 Severe hypertension.
6.2
6.2. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 2 Proteinuria/pre‐eclampsia.
6.3
6.3. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 3 Total reported fetal or neonatal death (including miscarriage).
6.4
6.4. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 4 Small‐for‐gestational age.
6.5
6.5. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 5 Preterm birth (< 37 weeks).
6.6
6.6. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 6 Maternal death.
6.7
6.7. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 7 Eclampsia.
6.8
6.8. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 8 HELLP syndrome.
6.9
6.9. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 9 Pulmonary oedema.
6.10
6.10. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 10 Need for additional antihypertensive drug/s.
6.11
6.11. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 11 Elective delivery (induction of labour + elective caesarean section).
6.12
6.12. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 12 Caesarean section.
6.13
6.13. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 13 Induction of labour.
6.14
6.14. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 14 Placental abruption.
6.15
6.15. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 15 Maternal side‐effects.
6.16
6.16. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 16 Changed/stopped drug due to side‐effects.
6.17
6.17. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 17 Admission to neonatal or intensive care nursery.
6.18
6.18. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 18 Respiratory distress syndrome.
6.19
6.19. Analysis
Comparison 6 Any antihypertensive versus calcium channel blocker (subgrouped by class of drug), Outcome 19 Neonatal hypoglycaemia.
7.1
7.1. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 1 Severe hypertension.
7.2
7.2. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 2 Proteinuria/pre‐eclampsia.
7.3
7.3. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 3 Total reported fetal or neonatal death (including miscarriage).
7.4
7.4. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 4 Small‐for‐gestational age.
7.5
7.5. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 5 Preterm birth (< 37 weeks).
7.6
7.6. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 6 Maternal death.
7.7
7.7. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 7 Severe pre‐eclampsia.
7.8
7.8. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 8 Eclampsia.
7.9
7.9. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 9 HELLP syndrome.
7.10
7.10. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 10 Pulmonary oedema.
7.11
7.11. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 11 Need for additional antihypertensive drug/s.
7.12
7.12. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 12 Elective delivery (induction of labour + elective caesarean section).
7.13
7.13. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 13 Caesarean section.
7.14
7.14. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 14 Induction of labour.
7.15
7.15. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 15 Antenatal hospital admission.
7.16
7.16. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 16 Placental abruption.
7.17
7.17. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 17 Maternal side‐effects.
7.18
7.18. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 18 Changed/stopped drugs due to maternal side‐effects.
7.19
7.19. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 19 Admission to neonatal or intensive care nursery.
7.20
7.20. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 20 Respiratory distress syndrome.
7.21
7.21. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 21 Neonatal hypoglycaemia.
7.22
7.22. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 22 Neonatal bradycardia.
7.23
7.23. Analysis
Comparison 7 Any antihypertensive versus beta blocker (subgrouped by class of drug), Outcome 23 Neonatal jaundice.
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    Lailler G, Grave C, Gabet A, Regnault N, Deneux-Tharaux C, Kretz S, Mounier-Vehier C, Tsatsaris V, Plu-Bureau G, Blacher J, Olié V. Lailler G, et al. J Am Heart Assoc. 2023 Mar 7;12(5):e027266. doi: 10.1161/JAHA.122.027266. Epub 2023 Feb 27. J Am Heart Assoc. 2023. PMID: 36847049 Free PMC article.
  • [Austrian Consensus on High Blood Pressure 2019].
    Weber T, Arbeiter K, Ardelt F, Auer J, Aufricht C, Brandt MC, Dichtl W, Ferrari J, Föger B, Henkel M, Hohenstein-Scheibenecker K, Horn S, Kautzky-Willer A, Kepplinger E, Knoflach M, Koppelstätter C, Mache C, Marschang P, Mayer G, Metzler B, Oberbauer R, Obermair F, Obermayer-Pietsch B, Perl S, Pilz S, Prischl FC, Podczeck-Schweighofer A, Rebhandl E, Rohla M, Roller-Wirnsberger R, Saely CH, Siostrzonek P, Slany J, Stoschitzky K, Waldegger S, Wenzel RR, Weiss T, Wirnsberger G, Winhofer-Stöckl Y, Zweiker D, Zweiker R, Watschinger B; Österreichische Gesellschaft für Hypertensiologie; Österreichische Atherosklerosegesellschaft; Österreichische Diabetes Gesellschaft; Österreichische Gesellschaft für Internistische Angiologie; Österreichische Gesellschaft für Nephrologie; Österreichische Kardiologische Gesellschaft; Österreichische Gesellschaft für Neurologie; Österreichische Schlaganfall-Gesellschaft; Österr. Gesellschaft für Allgemeinmedizin; Österr. Gesellschaft für Geriatrie; Österreichische Gesellschaft für Endokrinologie und Stoffwechsel; Österreichische Gesellschaft für Innere Medizin; Österreichische Gesellschaft für Kinder- und Jugendheilkunde. Weber T, et al. Wien Klin Wochenschr. 2019 Nov;131(Suppl 6):489-590. doi: 10.1007/s00508-019-01565-0. Wien Klin Wochenschr. 2019. PMID: 31792659 German.
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    Hauspurg A, Jeyabalan A. Hauspurg A, et al. Am J Obstet Gynecol. 2022 Feb;226(2S):S1211-S1221. doi: 10.1016/j.ajog.2020.10.027. Epub 2021 Jul 7. Am J Obstet Gynecol. 2022. PMID: 35177218 Free PMC article. Review.
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References

References to studies included in this review

Argentina 1985 {published data only}
    1. Voto L, Lapidus A, Neira J, Margulies M. Atenolol vs alpha methyldopa in the treatment of hypertension in pregnancy. 5th International Congress for the International Society for the study of Hypertension in Pregnancy; 1986 July 7‐10; Nottingham, UK. 1986:138.
    1. Voto LS, Lapidus AM, Neira J, Margulies M. Treatment of hypertension during pregnancy: atenolol versus alpha‐methyldopa [Tratamiento de la hipertensión en el embarazo: Atenolol versus Alfa Metildopa]. Obstetricia y Ginecología Latino‐Americanas 1985;43(9‐10):335‐41.
Argentina 1987 {published data only}
    1. Voto LS, Zin C, Neira J, Lapidus AM, Margulies M. Ketanserin versus alpha methyldopa in the treatment of hypertension during pregnancy: a preliminary report. Journal of Cardiovascular Pharmacology 1987;10(Suppl 3):S101‐S103. - PubMed
Argentina 1988 {published data only}
    1. Casavilla F, Vega HR. Prospective and randomized study on mepindolol and alpha‐methydopa efficacy in arterial hypertension (AH) treatment during pregnancy. World Congress of Gynecology and Obstetrics; 1988 October 23‐28; Brazil. 1988:182.
Australia 1983 {published data only}
    1. Livingstone I, Craswell PW, Bevan EB, Smith MT, Eadie MJ. Propranolol in pregnancy ‐ three‐year prospective study. Clinical and Experimental Hypertension 1983;2:341‐50. - PubMed
Australia 1985a {published data only}
    1. Gallery ED, Gyory AZ. Antihypertensive therapy in pregnancy [abstract]. Kidney International 1984;26(2):232.
    1. Gallery ED, Hunyor SN, Saunders DM, Gyory AZ. A randomized trial of oxyprenolol and a‐methyl dopa in therapy of hypertension in pregnancy. 1st Congress of the International Society of Hypertension in Pregnancy; 1978 September 27‐29; Dublin, Ireland. 1978:88.
    1. Gallery ED, Ross MR, Gyory AZ. Antihypertensive treatment in pregnancy: analysis of different responses to oxprenolol and methyldopa. BMJ 1985;291:563‐6. - PMC - PubMed
    1. Gallery ED, Saunders DM, Hunyor SN, Gyory AZ. Randomised comparison of methyldopa and oxprenolol for treatment of hypertension in pregnancy. BMJ 1979;1:1591‐4. - PMC - PubMed
Australia 2001 {published and unpublished data}
    1. Davis G, Brown M. Re: glyceryl trinitrate (GTN) patches are unsuitable in hypertensive pregnancy. Australian Journal of Obstetrics and Gynaecology 2001; Vol. 41, issue 4:474. - PubMed
Brazil 1985 {published data only}
    1. Kahhale S, Carrara W, Barros AC, Zugaib M, Neme B. A comparative study between treated (beta‐blocker pindolol) and untreated chronic hypertension. 4th World Congress of the International Society for the Study of Hypertension in Pregnancy; 1984 June 18‐21; Amsterdam, The Netherlands. 1984:56.
    1. Kahhale S, Zugaib M, Carrara W, Paula FJ, Sabbaga E, Neme B. Comparative study of chronic hypertensive pregnant women treated and non‐treated with pindolol [Estudio comparativo de gestantes hipertensas crônicas tratadas e näo tratadas com betabloqueador pindolol]. Ginecologia e Obstetrícia Brasileiras 1985;8(2):85‐9.
Brazil 1988 {published and unpublished data}
    1. Freire S, França LA, Rau de Almeida Callou M, Alves de Oliveira JE, Barbosa Filho J. Comparative study with pindolol and methyldopa in pregnant women with chronic hypertension [Estudo comparativo com pindolol e metildopa em gestantes com hipertensão arterial crônica]. Jornal Brasileiro de Ginecologia 1988;98(3):157‐60.
Brazil 2000a {published and unpublished data}
    1. Nascimento DJ. [Avaliaçäo do uso do verapamil em gestantes com formas näo graves de doença hipertensiva vascular crônica] Evaluation of the use of Verapamil with Non‐serious Form of Chronic Vascular Hypertension Disease During Pregnancy [Doctoral thesis]. Brazil: Facultade Evangélica de Medicina do Paraná, 2000.
Brazil 2016 {published data only}
    1. Trapani A Jr, Goncalves LF, Trapani TF, Vieira S, Pires M, Pires MM. Perinatal and hemodynamic evaluation of sildenafil citrate for preeclampsia treatment: A randomized controlled trial. Obstetrics and Gynecology 2016;128(2):253‐9. - PubMed
Caribbean Is.1990 {published and unpublished data}
    1. Plouin PF, Breart G, Llado J, Dalle M, Keller ME, Goujon H, et al. A randomized comparison of early with conservative use of antihypertensive drugs in the management of pregnancy‐induced hypertension. British Journal of Obstetrics and Gynaecology 1990;97:134‐41. - PubMed
Finland 1988b {published data only}
    1. Yla‐Outinen A, Tuimala R. Management of pregnancy induced hypertension by using nifedipine ‐ a prospective randomized trial. 6th International Congress of the International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:133.
France 1987 {published data only}
    1. Plouin PF, Breart G, Maillard F, Papiernik E, Relier JP, Labetolol Methyldopa Study Group. Antihypertensive efficacy and perinatal safety of labetalol in the treatment of hypertension in pregnancy: a randomised comparison to methyldopa [Effets maternels et securite perinatale du labetalol dans le traitement des hypertensions de la grossesse. Comparaison a la methyldopa par un essai cooperatif randomise]. Archives des Maladies du Coeur 1987;80:952‐5. - PubMed
    1. Plouin PF, Breart G, Maillard F, Papiernik E, Relier JP, the Labetolol Methyldopa Study Group. Comparison of antihypertensive efficacy and perinatal safety of labetalol and methyldopa in the treatment of hypertension in pregnancy: a randomized controlled trial. British Journal of Obstetrics and Gynaecology 1988;95:868‐76. - PubMed
France 1988a {published data only}
    1. Blazquez, Lardoux H, Leperlier E. Randomized and comparative study of methyl dopa (MD), acebutolol (ACE) and labetalol for the treatment of moderate hypertension during pregnancy (HDP). 6th International Congress, International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:100.
    1. Lardoux H, Blazquez G, Leperlier E, Gerard J. Randomized and comparative study of methyldopa (MD), acebutolol (ACE) and labetalol for the treatment of moderate hypertension during pregnancy (HDP) [Essai ouvert, comparatif, avec tirage au sort pour le traitement de l'HTA gravidique moderee: methyldopa, acetbutolol, labetalol]. Archives des Maladies du Coeur 1988;91:137‐40. - PubMed
France 1990 {published data only}
    1. Bonnin P, Mintz P, Kedra AW, Pruna A, Ciraru‐Vigneron N, Savin E, et al. Effects of nifedipine and atenolol on the fetal‐maternal circulation in moderate hypertension in pregnancy [Effets de la nifedipine et de l'atenolol sur les circulations foeto‐maternelles en cas d'hypertension arterielle gravidique moderee]. Therapie 1990;45(6):525.
    1. Ciraru‐Vigneron N, Pruna A, Akposso K, Bonnin P, Kedra W, Mintz P, et al. Comparison of the effects of nefedipine and atenolol in the treatment of uncomplicated hypertension in pregnancy [Comparaison des effets de la nifedipine et de l'atenolol dans le traitement de l'hypertension arterielle gravidique non compliquée]. Therapie 1992;47(3):221.
    1. Ciraru‐Vigneron N, Pruna A, Mintz P, Bonnin P, Lefevre V, Beaufils M, et al. Comparison of nifedipine and atenolol in treatment of moderate pregnancy hypertension. Proceedings of the 7th World Congress of Hypertension in Pregnancy; 1990; Perugia, Italy. 1990:340.
    1. Mintz P, Ciraru‐Vigneron N, Ravina JH, Pruna A, Idatte JH, Bonnin P, et al. Comparison of the effects of nifedipine and atenolol in the treatment of non‐complicated hypertension in pregnancy [Comparaison des effets de la nifedipine et de l'atenolol dans le traitement de l'hypertension arterielle gravidique non compliquée]. Therapie 1989;44(6):461.
France 1994 {published data only}
    1. Jannet D, Carbonne B, Sebban E, Milliez J. Nicardipine vs metoprolol in the treatment of hypertension during pregnancy: a randomized comparative trial. International Journal of Gynecology & Obstetrics 1995;49:225. - PubMed
    1. Jannet D, Carbonne B, Sebban E, Milliez J. Nicardipine vs metoprolol in the treatment of hypertension during pregnancy: a randomized comparative trial. Obstetrics & Gynecology 1994;84:354‐9. - PubMed
Hong Kong 1990 {published data only}
    1. Li CY, Lao TT, Yu KM, Wong SP, Leung CF. The effect of labetalol on mild pre‐eclampsia. Proceedings of the 7th World Congress of Hypertension in Pregnancy; 1990; Perugia, Italy. 1990:191.
Hong Kong 1993 {published data only}
    1. Yuen FT, Mo YP, Yin LC, Terence L. A double‐blind randomised placebo controlled trial of labetalol in the treatment of mild pregnancy induced hypertension. Proceedings of the 2nd International Scientific Meeting of the Royal College of Obstetricians and Gynaecologists; 1993; Hong Kong, Singapore. 1993.
India 1992 {published data only}
    1. Oumachigui A, Verghese M, Balachander J. A comparative evaluation of metoprolol and methyldopa in the management of pregnancy induced hypertension. Indian Heart Journal 1992;44:39‐41. - PubMed
India 2002 {published data only}
    1. Banerjee G, Chatterjee D, Chatterjee A, Mukherjee P, Das A. A randomized controlled trial on use of nimodipine in mild P.I.H. Journal of Obstetrics and Gynecology of India 2002;52(4):44‐6.
India 2011 {published data only}
    1. Pandey K, Gupta N, Gupta R, Gupta S. Comparing obstetric outcome using labetalol/methyldopa in pregnancy induced hypertension. 54th All India Congress of Obstetrics and Gynaecology; 2011 January 5‐9; Hyderabad, Andhra Pradesh, India. 2011:46.
India 2012 {published data only}
    1. Molvi SN, Mir S, Rana VS, Jabeen F, Rauoof A. Role of antihypertensive therapy in mild to moderate pregnancy‐induced hypertension: A prospective randomized study comparing labetalol with alpha methyldopa. Archives of Gynecology and Obstetrics 2012;285(6):1553‐62. - PubMed
India 2013a {published data only}
    1. Srivastava B, Usha R, Bhardwaj R, Gaur S, Joshi G, Nag P. Comparative study of efficacy and adverse effect of labetalol and methyldopa in patients with pregnancy ‐induced hypertension. Indian Journal of Pharmacology 2013; Vol. 45.
India 2013b {published data only}
    1. Aparna J. A randomized, double‐blind, comparative trial of nifedipine and methyldopa in moderate pregnancy induced hypertension. Der Pharmacia Lettre 2013;5(4):274‐7.
India 2013c {published data only}
    1. Subhedar V, Inamdar S, Hariharan C, Subhedar S. Comparison of efficacy of labetalol and methyldopa in patients with pregnancy‐induced hypertension. International Journal of Reproduction, Contraception, Obstetrics and Gynecology 2013;2(1):27‐34.
India 2015a {published data only}
    1. Babbar K, Armo M, Bhanja RL. A comparative study of efficacy of antihypertensive drugs and feto‐maternal outcome in the treatment of pregnancy induced hypertension. Journal of Reproduction, Contraception, Obstetrics and Gynecology 2015;4(6):1846‐52.
India 2015b {published data only}
    1. Singhal S, Gupta AK. A comparative randomized controlled parallel group study of efficacy and tolerability of labetalol versus methyldopa in the treatment of mild pre‐eclampsia. Internatiional Journal of Basic and Clinical Pharmacology 2015; Vol. 4, issue 3:442‐5.
Ireland 1991 {published and unpublished data}
    1. Blake S, MacDonald D. The prevention of the maternal manifestations of pre‐eclampsia by intensive antihypertensive treatment. British Journal of Obstetrics and Gynaecology 1991;98:244‐8. - PubMed
Israel 1986a {published data only}
    1. Ellenbogen A, Jaschevatzky O, Davidson A, Anderman S, Grunstein S. Management of pregnancy‐induced hypertension with pindolol ‐ comparative study with methyldopa. International Journal of Gynecology & Obstetrics 1986;24:3‐7. - PubMed
    1. Jaschevatzky OE, Davidson A, Ellenbogen A, Anderman S, Grunstein S. Comparative study of pindolol and methyldopa and transplacental cross of pindolol in PIH. 5th International Congress of the International Society for the study of Hypertension in Pregnancy; 1986 7‐10 July; Nottingham, England. 1986:137.
Israel 1986b {published data only}
    1. Rosenfeld J, Bott‐Kanner G, Boner G, Nissenkorn A, Friedman S, Ovadia J, et al. Treatment of hypertension during pregnancy with hydralazine monotherapy or with combined therapy with hydralazine and pindolol. European Journal of Obstetrics & Gynecology and Reproductive Biology 1986;22:197‐204. - PubMed
Israel 1992a {published data only}
    1. Bar J, Hirsch M, Friedman S, Fuchs J, Ovadia J, Bott‐Kanner G. The effect of beta‐adrenergic blocker pindolol on platelet function in chronic hypertensive pregnancies. Proceedings of 9th International Congress, International Society for the Study of Hypertension in Pregnancy; 1994 March 15‐18; Sydney, Australia. 1994:155.
    1. Bott‐Kanner G, Hirsch M, Boner G, Ovadia J, Modan M, Friedmann S, et al. Evaluation of antihypertensive therapy (AHT) in the management of hypertension in pregnancy (HP). 6th International Congress of the International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:11.
    1. Bott‐Kanner G, Hirsch M, Friedman S, Boner G, Ovadia J, Merlob P, et al. Antihypertensive therapy in the management of hypertension in pregnancy ‐ a clinical double‐blind study of pindolol. Clinical and Experimental Hypertension 1992;B11:207‐20.
    1. Hirsch M, Bar J, Bott‐Kanner G, Kaplan B, Fuchs J, Ovadia J. Effect of the beta‐adrenergic blocker pindolol on platelet function in chronic hypertensive pregnancy. Hypertension in Pregnancy 1996;15:193‐202.
Israel 1995 {published data only}
    1. Paran E, Baile Y, Holzberg G, Masor M, Zmora E, Insler V. Treatment of hypertension in pregnancy: different regime, different outcome. 6th International Congress of the International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:105.
    1. Paran E, Holzberg G, Mazor M, Zmora E, Insler V. Beta‐adrenergic blocking agents in the treatment of pregnancy‐induced hypertension. International Journal of Clinical Pharmacology and Therapeutics 1995;33:119‐23. - PubMed
    1. Paran E, Maisner I, Holzberg G, Mazor M, Zmora E, Biale Y, et al. Beta‐blocker treatment of PIH correlated with uteroplacental blood flow measurement. 6th International Congress, International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:109.
Italy 1997 {published data only}
    1. Catalano D, Ercolano S, Pollio F, Ascione L, Russo C, Santi B, et al. Evaluation of nifedipine monotherapy in the management of pregnancy hypertension [Valuazione della monoterapia con nifedipina nel management della gestosi EPH]. Giornale Italiano Di Ostetricia e Ginecologia 1997;6:373‐5.
Italy 1998 {published data only}
    1. Bortolus R, Ricci E, Chatenoud L, Parazzini F. Nifedipine administered in pregnancy: effect on the development of children at 18 months. BJOG: an international journal of obstetrics and gynaecology 2000;107:792‐4. - PubMed
    1. Gruppo di Studio Ipertensione in Gravidanza. Nifedipine versus expectant management in mild to moderate hypertension in pregnancy. British Journal of Obstetrics and Gynaecology 1998;105:718‐22. - PubMed
    1. Luchini L, Bortolus R, Parazzini F. Multicentric, randomized, clinical trial on the efficacy of long‐acting nifedipine in improving the prognosis of pregnancy in women with mild or moderate chronic or pregnancy‐induced hypertension. Journal of Nephrology 1991;6:51‐4.
Italy 1999 {published and unpublished data}
    1. Neri I, Ternelli G, Facchinetti F, Volpe A. Effectiveness of oral nifedipine and transdermal glyceryltrinitrate on 24‐hours blood pressure values in pregnancy‐induced hypertension. Hypertension in Pregnancy 2000;19(Suppl 1):O65.
    1. Neri I, Valensise H, Fachinetti F, Menghini S, Romanini C, Volpe A. 24‐hour ambulatory blood pressure monitoring: a comparison between transdermal glyceryl‐trinitrate and oral nifedipine. Hypertension in Pregnancy 1999;18:107‐13. - PubMed
Italy 2000 {published and unpublished data}
    1. Borghi C, Degli Esposti D, Cassani A, Immordino V, Bovicelli L, Ambrosioni E. The treatment of hypertension in pregnancy. Journal of Hypertension 2002;20(Suppl 2):S52‐S56. - PubMed
    1. Borghi C, Immordino V, Degli Esposti D, Boschi S, Cassani A, Bentivenga C, et al. Comparison between nifedipine‐gits and methyldopa on blood pressure control, utero‐placental hemodynamic and fetal outcome in patients with pre‐eclampsia. Hypertension in Pregnancy 2000;19(Suppl 1):P8.
Pakistan 2016 {published data only}
    1. Sharif N, Usman I, Azhar T. Pregnancy induced hypertension; to compare efficacy of methyldopa and labetalol in management. Professional Medical Journal 2016; Vol. 23, issue 10:1187‐93.
Panama 2014 {published data only}
    1. Vigil‐De Gracia P, Dominguez L, Solis A. Management of chronic hypertension during pregnancy with furosemide, amlodipine or aspirin: a pilot clinical trial. Journal of Maternal‐Fetal & Neonatal Medicine 2014;27(13):1291‐4. - PubMed
South Africa 1991a {published data only}
    1. Odendaal HJ, Schabort I, Pattinson RC. Prazosin for the treatment of hypertension in pregnancy: a randomized control trial. In: Oxford Database of Perinatal Trials, Version 1.2, Disk Issue 6, Autumn. Chalmers I (ed). Oxford: Oxford University Press.1991.
South Africa 1993 {published data only}
    1. Eloff WJ. The use of nifedipine vs methyldopa in mild to moderate pregnancy associated hypertension. Proceedings of the 12th Conference on Priorities in Perinatal Care; 1993; South Africa. 1993:130‐3.
Spain 1988 {published data only}
    1. Torres Pons PJ, Roca M, Codina C, Cobo E, Cararach V, Gonzalez‐Merlo J. Labetalol in the treatment of mild hypertension in pregnancy. A double blind controlled trial. 6th International Congress, International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:102.
Sudan 2002 {published data only}
    1. Elhassan EM, Mirghani OA, Habour AB, Adam I. Methyldopa versus no drug treatment in the management of mild pre‐eclampsia. East African Medical Journal 2002;71(4):172‐5. - PubMed
Sweden 1984 {published and unpublished data}
    1. Bjorksten B, Finnstrom O, Wichman K. Intrauterine exposure to the beta‐adrenergic receptor‐blocking agent metoprolol and allergy. International Archives of Allergy and Immunology 1988;87:59‐62. - PubMed
    1. Finnstrom O, Ezitis J, Ryden G, Wichman K. Neonatal effects of beta‐blocking drugs in pregnancy. Acta Obstetricia et Gynecologica Scandinavica Supplement 1984;118:91‐3. - PubMed
    1. Ryden G, Karlberg BE, Wichman K. Metoprolol in the treatment of hypertension in pregnancy ‐ effect on the mother and foetus. 4th World Congress of the International Society for the study of Hypertension in Pregnancy; 1984 Jun 18‐21; Amsterdam, The Netherlands. 1984:38.
    1. Wichman K. Metoprolol in the treatment of mild to moderate hypertension in pregnancy ‐ effects on fetal heart activity. Clinical and Experimental Hypertension 1986;5:195‐202.
    1. Wichman K, Ezitis J, Finnstrom O, Ryden G. Metoprolol in the treatment of hypertension in pregnancy ‐ effect on the newborn baby. Clinical and Experimental Hypertension 1984;B3:153.
Sweden 1985 {published and unpublished data}
    1. Hogstedt S, Lindberg B, Lindeberg S, Ludviksson K, Sandstrom B. Effect of metoprolol on fetal heart rate patterns during pregnancy and delivery. Clinical and Experimental Hypertension 1984;B3:152.
    1. Högstedt S, Lindberg B, Lindberg S, Ludviksson K, Sandström B. Effect of metoprolol on fetal heart rate patterns during pregnancy and delivery. 4th World Congress of the International Society for the study of Hypertension in Pregnancy; 1984 June 18‐21; Amsterdam, The Netherlands. 1984:39.
    1. Högstedt S, Lindeberg S, Axelsson O, Lindmark G, Rane A, Sandström B, et al. A prospective controlled trial of metoprolol‐hydralazine treatment in hypertension during pregnancy. Acta Obstetricia et Gynecologica Scandinavica 1985;64:505‐10. - PubMed
    1. Lindeberg S, Axelsson O, Lindeberg BS, Lindmark G, Ludviksson K, Sandström B. Effect of metoprolol in combination with hydralazine on fetal heart rate patterns during hypertensive pregnancy and delivery. Clinical and Experimental Hypertension 1985;4(1):87‐94.
Sweden 1995 {published data only}
    1. Wide‐Swensson D, Ingemarsson I, Lunell NO, Lindberg B, Lindeberg S, Marsal K, et al. Calcium channel blockade (isradipine) in treatment of hypertension in pregnancy: a randomized placebo‐controlled study. International Journal of Obstetrics & Gynecology 1994;46:3. - PubMed
    1. Wide‐Swensson DH, Ingemarsson I, Lunell NO, Forman A, Skajaa K, Lindberg B. Calcium channel blockade (isradipine) in treatment of hypertension in pregnancy: a randomized placebo‐controlled study. American Journal of Obstetrics and Gynecology 1995;173:872‐8. - PubMed
UK 1968 {published data only}
    1. Leather HM, Humphreys DM, Baker P, Chadd MA. A controlled trial of hypotensive agents in hypertension in pregnancy. Lancet 1968;2:488‐90. - PubMed
UK 1976 {published data only}
    1. Cockburn J, Moar VA, Ounsted MK, Redman CW. Final report on study of hypertension during pregnancy: the effects of specific treatment on the growth and development of the children. Lancet 1982;1:647‐9. - PubMed
    1. Moar VA, Jefferies MA, Mutch LM, Ounsted MK, Redman CW. Neonatal head circumference and the treatment of maternal hypertension. British Journal of Obstetrics and Gynaecology 1978;85:933‐7. - PubMed
    1. Mutch LM, Moar VA, Ounsted MK, Redman CW. Hypertension during pregnancy, with and without specific hypotensive treatment. I. Perinatal factors and neonatal morbidity. Early Human Development 1977;1:47‐57. - PubMed
    1. Mutch LM, Moar VA, Ounsted MK, Redman CW. Hypertension during pregnancy, with and without specific hypotensive treatment. II The growth and development of the infant in the first year of life. Early Human Development 1977;1:59‐67. - PubMed
    1. Ounsted M. The children of women who had hypertension during pregnancy. In: Rubin PC editor(s). Hypertension in Pregnancy. Amsterdam: Elsevier Science Publishers B.V, 1988:341‐62.
UK 1980 {published data only}
    1. Lamming GD, Pipkin FB, Symonds EM. Comparison of the alpha and beta blocking drug, labetalol, and methyl dopa in the treatment of moderate and severe pregnancy‐induced hypertension. Clinical and Experimental Hypertension 1980;2:865‐95. - PubMed
    1. Lamming GD, Symonds EM. Comparison of the alpha and beta blocking drug labetalol and aldomet in the treatment of pregnancy induced hypertension. Proceedings of the 2nd Congress of the International Society for the Study of Hypertension in Pregnancy; 1980 December 1‐4; Cairo, Egypt. 1980:9.
    1. Lamming GD, Symonds EM. Use of labetalol and methyldopa in pregnancy‐induced hypertension. British Journal of Clinical Pharmacology 1979;8:217S‐222S. - PMC - PubMed
UK 1982 {published and unpublished data}
    1. Cameron AD, Walker JJ, Bonduelle M, Calder AA. A randomised trial of the antihypertensive agent, labetalol, against bed rest in pregnancy hypertension. Archives of Gynecology 1985;237(Suppl 1):295.
    1. Lang GD, Lowe GD, Walker JJ, Forbes CD, Calder AA. Increased blood viscosity in pre‐eclampsia: effect of treatment with labetalol. Thrombosis and Haemostasis 1983;50:156.
    1. Lang GD, Lowe GD, Walker JJ, Forbes CD, Prentice CR, Calder AA. Blood rheology in pre‐eclampsia and intrauterine growth retardation: effects of blood pressure reduction with labetalol. British Journal of Obstetrics and Gynaecology 1984;91:438‐43. - PubMed
    1. Walker J. Intrauterine Growth Retardation and Maternal Labetalol Treatment in a Random Allocation Controlled Study [MD thesis]. Scotland: University of Glasgow, 1992:141‐55.
    1. Walker JJ, Crooks A, Erwin L, Calder AA. Labetalol in pregnancy‐induced hypertension: fetal and maternal effects. In: Reilly A, Symonds EM editor(s). International Congress Series 591. Amsterdam: Excerpta Medica, 1982:148‐60.
UK 1983a {published data only}
    1. Reynolds B, Butters L, Evans J, Adams T, Rubin PC. First year of life after the use of atenolol in pregnancy associated hypertension. Archives of Disease in Childhood 1984;59:1061‐3. - PMC - PubMed
    1. Rubin PC, Butters L, Clark D, Sumner D, Belfield A, Pledger D, et al. Obstetric aspects of the use in pregnancy‐associated hypertension of the beta‐adrenoceptor antagonist atenolol. American Journal of Obstetrics and Gynecology 1984;150:389‐92. - PubMed
    1. Rubin PC, Butters L, Clark DM, Low RA, Reid JL. Atenolol in the management of hypertension during pregnancy. Drugs 1983;25:212‐4.
    1. Rubin PC, Butters L, Clark DM, Reynolds B, Sumner DJ, Steedman D. Placebo‐controlled trial of atenolol in treatment of pregnancy‐associated hypertension. Lancet 1983;1:431‐4. - PubMed
    1. Rubin PC, Butters L, Reynolds B, Low RAL. Atenolol in the management of pregnancy associated hypertension: obstetric and paediatric aspects. 4th World Congress of the International Society for the Study of Hypertension in Pregnancy; 1984 June 18‐21; Amsterdam, The Netherlands. 1984:41.
UK 1983b {published data only}
    1. Fidler J, Smith V, Fayers P, Swiet M. Randomised controlled comparative study of methyldopa and oxprenolol in treatment of hypertension in pregnancy. British Medical Journal 1983;286:1927‐30. - PMC - PubMed
    1. Fidler J, Smith V, Fayers P, Swiet M. Randomised controlled comparative study of methyldopa and oxprenolol in treatment of hypertension in pregnancy. Obstetrical and Gynecological Survey 1983;286:202‐5. - PMC - PubMed
UK 1984 {published data only}
    1. Thorley KJ. Atenolol: side effects in the newborn infant. British Medical Journal 1982;285:1116. - PMC - PubMed
    1. Thorley KJ. Randomised trial of atenolol and methyl dopa in pregnancy related hypertension. 4th World Congress of the International Society for the Study of Hypertension in Pregnancy; 1984 June 18‐21; Amsterdam, The Netherlands. 1984:53.
    1. Thorley KJ. Randomised trial of atenolol and methyl dopa in pregnancy related hypertension. Clinical and Experimental Hypertension 1984;133:168.
UK 1989 {published data only}
    1. Pickles C, Symonds E, Brinkman C. Effects of labetalol (L) vs placebo (P) on arterial pressure (AP) and forearm venous distensibility (FVD) in women with pregnancy induced hypertension (PIH). 5th International Congress of the International Society for the study of Hypertension in Pregnancy; 1986 7‐10 July; Nottingham, England. 1986:92.
    1. Pickles CJ, Broughton Pipkin F, Symonds EM. A randomised placebo controlled trial of labetalol in the treatment of mild to moderate pregnancy induced hypertension. Britisth Journal of Obstetrics and Gynaecology 1992;99:964‐8. - PubMed
    1. Pickles CJ, Symonds EM, Broughton Pipkin F. The fetal outcome in a randomized double‐blind controlled trial of labetalol vs placebo in pregnancy‐induced hypertension. British Journal of Obstetrics and Gynaecology 1989;96:38‐43. - PubMed
    1. Pickles CJ, Symonds EM, Broughton Pipkin F. The fetal outcome of early intervention therapy in pregnancy induced hypertension. A randomised, double‐blind controlled trial of labetalol vs placebo. 6th International Congress, International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:107.
UK 1990 {published and unpublished data}
    1. Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension during pregnancy. BMJ 1990;301:587‐9. - PMC - PubMed
UK 1992 {published and unpublished data}
    1. Cruickshank DJ, Campbell D, Robertson AA, MacGillivray I. Intra‐uterine growth retardation and maternal labetalol treatment in a random allocation controlled study. Journal of Obstetrics and Gynaecology 1992;12:223‐7.
    1. Cruickshank DJ, Campbell DM. Atenolol in essential hypertension during pregnancy. BMJ 1990;301:1103. - PMC - PubMed
    1. Cruickshank DJ, Robertson AA, Campbell DM, MacGillivray I. Does labetalol influence the development of proteinuria in pregnancy hypertension? A randomised controlled study. European Journal of Obstetrics & Gynecology and Reproductive Biology 1992;45:47‐51. - PubMed
    1. Cruickshank DJ, Robertson AA, Campbell DM, MacGillivray I. Maternal obstetric outcome measures in a randomised controlled study of labetalol in the treatment of hypertension in pregnancy. Clinical and Experimental Hypertension 1991;B10:333‐4.
UK 2009 {published data only}
    1. NCT00141310. A randomised, double‐blind, placebo‐controlled, flexible‐dose, parallel‐group study to evaluate the efficacy, safety and toleration of oral sildenafil citrate administered in the dose range of 20 ‐ 80 mg TID for the treatment of pre‐eclampsia. (PET). clinicaltrials.gov/ct2/show/record/NCT00141310 (first received: 30 August 2005).
    1. Samangaya RA, Mires G, Shennan A, Skillern L, Howe D, McLeod A, et al. A randomised, double‐blinded, placebo‐controlled trial of the phosphodiesterase type 5 inhibitor sildenafil in the treatment of preeclampsia. Hypertension in Pregnancy 2009;28:369‐82. - PubMed
    1. Samangaya RA, Wareing M, Skillern L, Baker PN. Phosphodiesterase inhibitor effect on small artery function in preeclampsia. Hypertension in Pregnancy 2011;30(2):144‐52. - PubMed
UK 2017 {published data only}
    1. EUCTR2013‐003144‐23‐GB. Pregnancy and chronic hypertension: nifedipine or labetalol as antihypertensive treatment ‐ PANDA. clinicaltrialsregister.eu/ctr‐search/search?query=eudract_number:2013‐00... (first received 30 October 2013).
    1. Webster L, Gill C, Seed P, Bramham K, Wiesender C, Nelson‐Piercy C, et al. Effect of antihypertensive treatment on placental, renal and endothelial biomarkers in pregnancy complicated by chronic hypertension. BJOG: an international journal of obstetrics and gynaecology 2017;124:12.
    1. Webster L, Myers J, Nelson‐Piercy C, Watt‐Coote I, Wiesender C, Seed PT, et al. Pregnancy and chronic hypertension: Nifedipine vs labetalol as antihypertensive treatment (the PANDA study). Pregnancy Hypertension 2016;6:141.
    1. Webster LM, Myers JE, Nelson‐Piercy C, Harding K, Cruickshank JK, Watt‐Coote I, et al. Labetalol versus nifedipine as antihypertensive treatment for chronic hypertension in pregnancy: a randomized controlled trial. Hypertension 2017;70(5):915‐22. - PubMed
    1. Webster LM, Myers JE, Nelson‐Piercy C, Watt‐Coote I, Wiesender C, Seed PT, Chappell LC. Pregnancy and chronic hypertension: Nifedipine vs labetalol as antihypertensive treatment (the Panda study). Ophthalmology 2016;6(3):141.
USA 1979 {published data only}
    1. Arias F, Zamora J. Antihypertensive treatment and pregnancy outcome in patients with mild chronic hypertension. Obstetrics & Gynecology 1979;53:489‐94. - PubMed
USA 1987a {published data only}
    1. Sibai BM, Gonzalez AR, Mabie WC, Moretti M. A comparison of labetalol plus hospitalization vs hospitalization alone in the management of preeclampsia remote from term. Obstetrics & Gynecology 1987;70:323‐7. - PubMed
USA 1987b {published data only}
    1. Weitz C, Khouzami V, Maxwell K, Johnson JW. Treatment of hypertension in pregnancy with methyldopa: a randomized double blind study. International Journal of Gynecology & Obstetrics 1987;25:35‐40. - PubMed
USA 1990a {published and unpublished data}
    1. Sibai BM. The need of hypertensive drugs in management of mild to moderate pregnant hypertension. Proceedings of the 7th World Congress of Hypertension in Pregnancy; 1990; Perugia, Italy. 1990:133.
    1. Sibai BM, Mabie WC, Shamsa F, Villar MA, Anderson GD. A comparison of no medication vs methyldopa or labetalol in chronic hypertension during pregnancy. American Journal of Obstetrics and Gynecology 1990;162:960‐7. - PubMed
USA 1992 {published data only}
    1. Barton JR, Mercer BM, Sibai BM. The effect of nifedipine on urinary excretion of calcium in preeclampsia. American Journal of Perinatology 1997;14:609‐12. - PubMed
    1. Sibai BM, Barton JR, Akl S, Sarinoglu C, Mercer BM. A randomized prospective comparison of nifedipine and bed rest vs bed rest alone in the management of preeclampsia remote from term. Amercian Journal of Obstetrics and Gynecology 1992;167:879‐84. - PubMed
    1. Sibai BM, Barton JR, Akl S, Sarinoglu C, Mercer BM. A randomized prospective comparison of nifedipine and bed rest vs bed rest alone in the management of preeclampsia remote from term. American Journal of Obstetrics and Gynecology 1992;166:280. - PubMed
Venezuela 1988 {published data only}
    1. Faneite PJ, Gonzalez X, Salazar G. Evaluation of antihypertensives in pregnancy: prospective randomized study of mepindolol and alpha methyldopa [Evaluación de antihipertensivos en embarazadas: Mepindolol y alfametildopa. Estudio prospectivo y randomizado]. Revista de Obstetricia y Ginecologia de Venezuela 1988;48:139‐43.

References to studies excluded from this review

Argentina 1990 {published data only}
    1. Voto LS, Quiroga CA, Lapidus AM, Catuzzi P, Uranga IF, Margulies M. Effectiveness of antihypertensive drugs in the treatment of hypertension in pregnancy. Clinical and Experimental Hypertension ‐ Part B Hypertension in Pregnancy 1990;9(3):339‐48.
Argentina 1994 {published data only}
    1. Fabregues G, Sure P, Knaudt S, Gonzalez Pena J, Esper R. The use of atenolol to prevent preeclampsia and superimposed preeclampsia. International Journal of Gynecology & Obstetrics 1994;46:95.
Australia 1985b {published data only}
    1. Henderson‐Smart DJ, Horvath JS, Phippard A, Korda A, Child A, Duggin GG, et al. Effect of antihypertensive drugs on neonatal blood pressure. Clinical and Experimental Pharmacology and Physiology 1984;11(4):351‐4. - PubMed
    1. Horvath JS, Henderson‐Smart DJ, Phippard A, Korda A, Child A, Duggin GG, et al. The effect of antihypertensive drugs on neonatal blood pressure. 4th World Congress of the International Society for the study of Hypertension in Pregnancy; 1984 June 18‐21; Amsterdam, The Netherlands. 1984:42.
    1. Horvath JS, Phippard A, Korda A, Henderson‐Smart D, Child A, Duggin GG, et al. A controlled trial comparing clonidine hydrochloride and alpha methyl dopa in pregnant women with hypertension. 4th World Congress of the International Society for the study of Hypertension in Pregnancy; 1984 June 18‐21; Amsterdam, The Netherlands. 1984:246.
    1. Horvath JS, Phippard A, Korda A, Henderson‐Smart DJ, Child A, Tiller DJ. Clonidine hydrochloride ‐ a safe and effective antihypertensive agent in pregnancy. Obstetrics & Gynecology 1985;66:634‐8. - PubMed
    1. Horvath JS, Phipparel A, Korda A, Henderson‐Smart D, Child A, Duggin GG, et al. A controlled trial comparing clonidine hydrochloride and alpha methyl dopa in pregnant women [abstract]. Kidney International 1984;26(2):233.
Australia 1991 {published and unpublished data}
    1. Phippard A, Fisher W, Child A, Henderson‐Smart D, Horvarth J, Korda A, et al. A randomized, placebo‐controlled study on the effect of therapy for mild to moderate hypertension in primigravidae. 6th International Congress of the International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:112.
    1. Phippard AF, Fischer WE, Horvath JS, Child AG, Korda AR, Henderson‐Smart DJ, et al. Early blood pressure control improves pregnancy outcome in primigravid women with mild hypertension. Medical Journal of Australia 1991;154:378‐82. - PubMed
Belgium 1988 {published data only}
    1. Loquet P, Buytaert P, Renier M. The influence of pindolol and atenolol on serial feto‐placental blood flow measurements in non‐proteinuric hypertension in pregnancy. 6th International Congress, International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:111.
    1. Renier M, Loquet P, Buytaert P. The influence of pindolol and atenolol on serial feto‐placental blood flow measurements in non‐proteinuric hypertension in pregnancy. Proceedings of the 11th European Congress of Perinatal Medicine;1988 April 10‐13; Rome, Italy. 1988.
Brazil 1997 {published data only}
    1. Pereira TS, Pereira CI, Junior JA, Netto HC. Influence of nifedipine on the fetal placental flow. Jornal Brasileiro de Ginecologia 1997;107(10):371‐80.
Brazil 2000b {published data only}
    1. Alves EA. Estudo prospectivo, comparativo da Isradipina e Atenolol no tratamento de gestantes hipertensas [Prospective, comparative study of isradipine and atenolol for the treatment of hypertensive pregnant women] [Doctoral Thesis]. Faculty of Medicine, University of São Paulo, 1998.
    1. Darcie S, Leone CR, Calil VM, Prescinotti EP, Kahhale S, Zugaib M. Glycemia in newborns of hypertensive mothers according to maternal treatment [Glicemia no recém‐nascido de mäe hipertensas de acordo com a terapêutica materna]. Revista do Hospital das Clínicas 2004;59(5):244‐0. - PubMed
    1. Kahhale S, Alves EA, Takiuti NH, Zugaib M. Efficacy and safety of isradipina and atenolol in hypertensive disorders in pregnancy [abstract]. Hypertension in Pregnancy 2000;19(1):98.
    1. Leone CR, Calil VM, Darcie S, Prescinotti EP, Kahhale S, Zugaib M. Growth of newborn of the mothers with hypertension during the first year of life: therapeutics in pregnancy on the newborn [Crescimento de recém‐nascidos de mäes hipertensas durante o primeiro ano de vida: influência da terapêutica materna]. Revista Paulista de Pediatría 2003;21(1):19‐26.
Brazil 2000c {published data only}
    1. Vasconcellos MJ, Chaves Netto H, Kahhale S. Incidence of small fetuses for the gestational age among chronic hypertensive women in use of verapamil (chronic oral use). Hypertension in Pregnancy 2000;19(Suppl 1):P166.
    1. Vasconcellos MJ, Chaves Netto H, Kahhale S. Verapamil: its effect on placental circulation in mild to moderate chronic hypertensive pregnant women. Hypertension in Pregnancy 2000;19(Suppl 1):P163.
    1. Vasconcellos MJ, Chaves Netto H, Kahhale S, Almeida PJ. Use of verapamil in chronic hypertensive pregnant women: flow analysis of uterine and umbilical artery [Uso do verapamil em gestantes hipertensas crônicas: análise do fluxo das artérias uterinas e umbilical]. Revista Brasileira de Ginecologia é Obstetrícia 2000;22(5):265‐74.
    1. Vasconcellos MJ, Chaves Netto H, Kahhale S, Almeida PJ. Verapamil use in chronic hypertension pregnant women. XVI FIGO World Congress of Obstetrics and Gynaecology; 2000 Sept 3‐8; Washington DC. Book 2. 2000:46.
China 1991 {published data only}
    1. Qian XH, Huang YL, Wu SP. Treatment of hypertension syndrome of pregnancy with ligustrazine. Chung Hsi I Chieh Ho Tsa Chih 1991;11(9):533‐4, 516. - PubMed
China 1993 {published data only}
    1. Hong YJ, Lin CF, Chen JC, Pan P, Wong KL, Wei TT. Nifedipine in preeclampsia for cesarean section. Ma Tsui Hsueh Tsa Chi (Acta Anaesthesiologica Sinica) 1993;31(1):43‐8. - PubMed
China 1998 {published data only}
    1. Li M, Yang M, Qiu X. The effect of nimodipine on retinal blood flow in pregnancy induced hypertension. Chung‐Hua Fu Chan Ko Tsa Chih 1998;33(7):397‐9. - PubMed
China 1999 {published data only}
    1. Wang Z, Song H. Clinical observation on therapeutical effect of prepared rhubarb in treating pregnancy induced hypertension. Chung‐Kuo Chung Hsi i Chieh Ho Tsa Chih 1999;19:725‐7. - PubMed
China 2000 {published data only}
    1. Yang X, Liu Y. The effect of nifedipine on postpartum blood loss in patients with pregnancy induced hypertension. Zhonghua Fu Chan Ke Za Zhi 2000;35(3):151‐2. - PubMed
China 2014 {published data only}
    1. Sun X, Wang K, Wang W, Li B. Clinical study on sildenafil in treatment of pregnant women with pulmonary arterial hypertension [Article in Chinese]. Zhonghua Fu Chan Ke Za Zhi 2014;49(6):414‐8. - PubMed
China 2017 {published data only}
    1. Xiao S, Zhang M, Liang Y, Wang D. Celastrol synergizes with oral nifedipine to attenuate hypertension in preeclampsia: a randomized, placebo‐controlled, and double blinded trial. Journal of the American Society of Hypertension 2017;11(9):598‐603. - PubMed
Cuba 1994 {published and unpublished data}
    1. Gómez Sosa E, Miró Maceo M, Alcade MT. Mild chronic hypertension: antihypertensive medication and maternal and perinatal results [Hipertensión crónica moderada: medicación antihipertensiva y resultados maternos y perinatales]. Revista Cubana de Medicina General Integral 1994;10(4):340‐3.
Czech Republic 1993 {published data only}
    1. Soucek M, Prasek J, Spinarova L. Atenolol and bisoprolol in the treatment of mild and moderately severe hypertension [Atenolol a bisoprolol v lécbe mírné a stredne tezké hypertenze]. Vnitrni Lekarstvi 1993;39(6):541‐8. - PubMed
Denmark 1991 {published data only}
    1. Rudnicki M, Frölich A, Fischer Rasmussen W, McNair P. The effect of magnesium on maternal blood pressure in pregnancy‐induced hypertension. Acta Obstetricia et Gynecologica Scandinavica 1991;70:445‐50. - PubMed
    1. Rudnicki M, Frölich A, Fischer‐Rasmussen W. Magnesium supplement in pregnancy‐induced hypertension: effects on maternal and neonatal magnesium and calcium homeostasis. Mineral and Electrolyte Metabolism 1991;17(6):399‐403. - PubMed
    1. Rudnicki M, Junge J, Frölich A, Ornvold K, Fischer‐Rasmussen W. Magnesium supplement in pregnancy‐induced hypertension. A clinicopathological study. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 1990;98(12):1123‐7. - PubMed
Denmark 2000 {published data only}
    1. Rudnicki M, Frølich A, Pilsgaard K, Nyrnberg L, Møller M, Sanchez M, et al. Comparison of magnesium and methyldopa for the control of blood pressure in pregnancies complicated with hypertension. Gynecologic and Obstetric Investigation 2000;49:231‐5. - PubMed
Dominican Republic 1992a {published data only}
    1. Cid‐Troncoso J, Pérez‐Pérez M, Jiménez JA, Núñez‐Diplan AM, Balbi M, Santana E. Nifedipine retard vs methyldopa in chronic hypertension with superimposed toxemia [Nifedipina retard vs. alfa‐metil‐dopa en la hipertensión arterial crónica mas toxemia agregada]. Revista Médica Dominicana 1992;53(2/3):76‐8.
Dominican Republic 1992b {published data only}
    1. Deschamps C, Guzman P, Mejia M, Sanchez Ramirez PB, Sanchez Beltre JE, Gomez Hernandez J. Comparison of hydralazine and alpha methyldopa in hypertension in pregnancy [Comparacion de hidralazina y alfametildopa en la hipertension durante el embarazo]. Acta Medica Dominicana 1992;14(6):222‐4.
Egypt 1988 {published data only}
    1. Salem HT, Ghanemah S, Seleem S, Sayed EH, Abdel‐Latif A, Chard T. Bromocriptine therapy in pre‐eclamptic toxaemia of pregnancy (PET). World Congress of Gynecology and Obstetrics; 1988 October 23‐28; Brazil. 1988:184.
Egypt 1993 {published data only}
    1. Ismail AA, Medhat I, Tawfic TAS, Kholeif A. Evaluation of calcium‐antagonist (Nifedipine) in the treatment of pre‐eclampsia. International Journal of Gynecology & Obstetrics 1993;40:39‐43. - PubMed
Egypt 1997 {published data only}
    1. Salem HT, Salah M, Kotb HI, Makarem MH, Mostafa SA, Mohamed SA. The use of specific opioid receptor antagonist (Naltrexone) in hypertensive pregnancy. Research Activities on Reproductive Health. Assiut: Assiut University, Faculty of Medicine, 1997:74.
Egypt 2009 {published data only}
    1. Tanbouli T, Mawsouf MN, Re L, Martinez‐Sanchez G, Saaed G, El SM, et al. Effect of ozone therapy on foetoplacental blood flow in hypertensive pregnant women. International Journal of Ozone Therapy 2009;8(2):211‐6.
Egypt 2017 {published data only}
    1. Abbas AM, NCT03213639. Use of esomeprazole in treatment of early onset preeclampsia:a double blind randomized, placebo‐controlled trial. clinicaltrials.gov/show/NCT03213639 (first received 21 Augsut 2017).
Finland 1988a {published data only}
    1. Tuimala R, Hartikainen‐Sorri AL. Randomised comparison of atenolol and pindolol for treatment of hypertension in pregnancy. Current Therapeutic Research 1988;44(4):579‐84.
    1. Tuimala R, Hartikainen‐Sorri AL. Treatment of hypertension during pregnancy by beta blocking agents. 4th World Congress of the International Society for the study of Hypertension in Pregnancy; 1984 June 18‐21; Amsterdam, The Netherlands. 1984:52.
Finland 1995 {published data only}
    1. Räsänen J, Joupilla P. Uterine and fetal hemodynamics and fetal cardiac function after atenolol and pindolol infusion. A randomized study. European Journal of Obstetrics & Gynecology and Reproductive Biology 1995;62:195‐201. - PubMed
Finland 1999 {published data only}
    1. Laivuori HM, Laakso M, Tikkanen MJ, Cacciatore B, Ylikorkala RO, Kaaja Rj. Short‐term metabolic effects of isradipine and metoprolol in pre‐eclampsia. Journal of Hypertension 1999;17(8):1189‐94. - PubMed
France 1986 {published data only}
    1. Fievet P, Esper N, Gueroult JF, Gueroult JC, Fournier A. Comparative study of clonidine and labetalol in severe hypertension induced by pregnancy. Congress of the International Society for the Study of Hypertension in Pregnancy. 7‐10 July 1986; Vol. Nottingham, England:136.
France 1988b {published data only}
    1. Madonna O, M'Pio I, Labeeuw M, Pozet N, Zech P. Evaluation of renal function in pregnant hypertensives under treatment. A comparison between methyldopa, pindolol and atenolol. 6th International Congress of the International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:260.
Germany 2012 {published data only}
    1. Groten T, Fitzgerald J, Lehmann T, Schneider U, Kahler C, Schleussner E. Reduction of preeclampsia related complications with the NO‐donor penterythriltetranitrat (petn) in risk pregnancies ‐ A prospective randomized double‐blind placebo pilot study. Pregnancy Hypertension 2012;2(3):181. - PubMed
Hungary 1999 {published data only}
    1. Tamás P, Csermely T, Ertl T, Vizer M, Szabó I, Prievara FT. Calcium dobesilate lowers the blood pressure in mild to moderate midtrimester hypertension: a pilot study. Gynecologic and Obstetric Investigation 1999;47:210‐3. - PubMed
    1. Tamás P, Csermely T, Szabó EI. Doxium ‐ a novel drug in the management of gestational hypertension?. 16th European Congress of Perinatal Medicine; 1998 June 10‐13; Zagreb. 1998.
    1. Tamás P, Szabó I, Szekely J, Csermely T, Prievara FT, Nemeth L, et al. Effects of doxium 500(tm) in gestational hypertension [A Doxium 500 (R) hatasanak vizgalata terhessegi hypertoniaban (kettos vak, placebo‐kontrollalt tanulmany)]. Magyar Noorvosok Lapja 1997;60:181‐7.
India 1999 {published data only}
    1. Shenoy S, Chandrika D, Pisharody R. RCT of low dose aspirin to prevent the progression of pregnancy induced hypertension grade A to B. Journal of Clinical Epidemiology 1999;52(Suppl 1):28S.
India 2012a {published data only}
    1. Verma R, Lahon K, TonpaY SD, Kale VJ. A comparative randomised controlled parallel group study of maternal, fetal and neonatal outcomes of labetalol versus methyldopa in the treatment of new onset hypertension during pregnancy. International Journal of Pharma & Bio Sciences 2012;3(1):201‐11.
    1. Verma R, Lahon K, Tonpay SD, Kale VJ, Jaim DK. A comparative randomised controlled parallel group study of efficacy and tolerability outcomes of labetalol versus methyldopa in the treatment of new onset hypertension during pregnancy. International Journal of Life Science & Pharma Research 2012;2(1):L23‐31.
India 2012b {published data only}
    1. Dasgupta S. Does prophylactic magnesium sulphate in mild preeclampsia reduce umbilical artery pulsatility index? A randomized placebo controlled trial. Clinical Trials Registry ‐ India (http://www.ctri.nic.in) (accessed 8 July 2011) 2011.
    1. Dasgupta S, Ghosh D, Seal SL, Kamilya G, Karmakar M, Saha D. Randomized controlled study comparing effect of magnesium sulfate with placebo on fetal umbilical artery and middle cerebral artery blood flow in mild preeclampsia at >= 34 weeks gestational age. Journal of Obstetrics and Gynaecology Research 2012;38(5):763‐71. - PubMed
India 2013d {published data only}
    1. Bracken H. Oral antihypertensive regimens for management of hypertension in pregnancy. clinicaltrials.gov/ct2/show/NCT01912677 (first received 29 July 2013).
    1. Mundle S, CTRI/2013/08/003866. Oral antihypertensive regimens for management of hypertension in pregnancy. http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=7167 (first received 2 August 2013).
India 2015c {published data only}
    1. Easterling T, Bracken H, Mundle S, Magee L, vonDadelszen P, Winikoff B. Oral antihypertensive regimens for management of severe hypertension in pregnancy: Results from a pilot study in India. Pregnancy Hypertension 2015;5(1):120.
India 2015d {published data only}
    1. Gainder S, Thakur M, Saha SC, Prakash M. To study the changes in maternal and fetal hemodynamics with intravenous labetalol or nifedipine in acute severe hypertension. Pregnancy Hypertension 2015;5(1):30. - PubMed
India 2016 {published data only}
    1. Mujawar JR, Patel SS. Circulating biomarkers of oxidative stress in preeclampsia and efficacy of antioxidant vitamin C supplementation. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2016;7(1):1498‐506.
Iran 2000 {published and unpublished data}
    1. Yassae F. A comparison of the effect of nifedipine and hydralazine in treatment of pregnancy induced hypertension. XVI FIGO World Congress of Obstetric and Gynecology (Book 3); 2000 Sept 3‐8; Washington DC, USA. 2000:93.
Iran 2005 {published data only}
    1. Ghahiri A, Berjis K. A comparison between intravenous magnesium sulfate and oral magnesium chloride in mild preeclampsia. Journal of Research in Medical Sciences 2005;10(1):6‐9.
Iran 2012 {published data only}
    1. NCT01674127. Effect of methyldopa on uterine artery diameter in pregnant women with mild preeclampsia. clinicaltrials.gov/ct2/show/record/NCT01674127 (first received 24 August 2012).
Iran 2016 {published data only}
    1. IRCT201602067676N5. Pregnancy outcomes with chronic hypertension on different antihypertensive therapy. http://en.search.irct.ir/view/28468 (first received 23 February 2016).
Israel 1988 {published data only}
    1. Davidson A, Ellenbogen A, Jaschevatzky O, Attias Y, Anderman S, Grunstein S. Randomized comparison of pindolol and atenolol for treatment of hypertension during pregnancy. 6th International Congress of the International Society for the Study of Hypertension in Pregnancy; 1988 May 22‐26; Montreal, Quebec, Canada. 1988:99.
Israel 1992b {published data only}
    1. Meizner I, Paran E, Katz M, Holcberg G, Insler V. Flow velocity analysis of umbilical and uterine artery flow in pre‐eclampsia treated with propranolol or pindolol. Journal of Clinical Ultrasound 1992;20:115‐9. - PubMed
Israel 1999 {published data only}
    1. Thaler I, Amit A, Kamil D, Itskovitz‐Eldor J. The effect of isosorbide dinitrate on placental blood flow and maternal blood pressure in women with pregnancy induced hypertension. American Journal of Hypertension 1999;12(4):341‐7. - PubMed
Italy 1986 {published data only}
    1. Martinelli P, Ferrara LA, Pasanisi F, Arpaia F, Paladini D, Mancini M. Nifedipine and atenolol in the treatment of pregnancy associated hypertension. 5th International Congress of the International Society for the Study of Hypertension in Pregnancy; 1986 July 7‐10; Nottingham, England. 1986:128.
Italy 1988 {unpublished data only}
    1. Pello L. Multicentric trial on the treatment of the hypertension in pregnancy [Ricerca multicéntrica sul trattamento del'ipertenzione in gravidanza]. Personal communication 1988.
Italy 1990a {published data only}
    1. Marlettini MG, Crippa S, Morselli‐Labate AM, Contarini A, Orlandi C. Randomised comparison of calcium antagonists and beta‐blockers in the treatment of pregnancy‐induced hypertension. Current Therapeutic Research, Clinical and Experimental 1990;48(4):684‐94.
    1. Orlandi C, Marlettini MG, Cassani A, Crippa S. Antihypertensive therapy in pregnancy. Proceedings of the 11th European Congress of Perinatal Medicine; 1988; Rome, Italy. 1988:271.
Italy 1990b {published data only}
    1. Iorio R, Horvath S, Marinoni E, Manzari G, Martinico E, Bresadola M. Use of a thromboxane receptor inhibitor in pregnancy‐induced hypertension. Proceedings of the 7th World Congress of Hypertension in Pregnancy; 1990; Perugia, Italy. 1990.
Italy 2000a {published data only}
    1. Picciolo C, Roncaglia N, Neri I, Pasta F, Arreghini A, Facchinetti F. Nitric oxide in the prevention of pre‐eclampsia. Prenatal and Neonatal Medicine 2000;5:212‐5.
Italy 2001 {published data only}
    1. Scarpellini F, Sbracia M, Lecchini S, Bolis P. Nitric oxide donor treatment reduces apoptosis in placental vessels of pregnancy induced hypertension [abstract]. American Journal of Obstetrics and Gynecology 2001;185(6 Suppl):S177.
Italy 2004 {published data only}
    1. Neri I, Venturini P, Battista Allais G, Facchinetti F. Acupuncture plus alfa‐metildopa in the treatment of chronic hypertension: a protocol design [abstract]. Hypertension in Pregnancy 2004;23(Suppl 1):54.
Italy 2006 {published data only}
    1. Facchinetti F, Piccinini F, Pizzi C, Bukowski R, Volpe A, Saade G. Effect of arginine supplementation in patients with gestational hypertension. American Journal of Obstetrics and Gynecology 2002;187(6):S213.
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Italy 2008 {published data only}
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Italy 2010 {published data only}
    1. Neri I, Monari F, Sgarbi L, Berardi A, Masellis G, Facchinetti F. L‐Arginine supplementation in women with chronic hypertension: Impact on blood pressure and maternal and neonatal complications. Journal of Maternal‐Fetal and Neonatal Medicine 2010;23(12):1456‐60. - PubMed
Italy 2012 {published data only}
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Japan 1997 {published data only}
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Japan 2016b {published data only}
    1. Koneoh E, JPRN‐UMIN000020686. Statin therapy for preeclampsia. upload.umin.ac.jp/cgi‐open‐bin/ctr_e/ctr_view.cgi?recptno=R000023870 (date received 22 January 2016).
Japan 2017 {published data only}
    1. JPRN‐UMIN000027270. A study on prevention of hypertensive disorders of pregnancy who have a history of severe hypertensive disorders of pregnancy ‐pre‐test for multi center trial. upload.umin.ac.jp/cgi‐open‐bin/ctr_e/ctr_view.cgi?recptno=R000031037 (first received 15 May 2017).
Kuwait 1995 {published data only}
    1. El‐Qarmalawi AM, Morsy AH, Al‐Fadly A, Obeid A, Hashem M. Labetalol vs methyldopa in the treatment of pregnancy‐induced hypertension. International Journal of Gynecology & Obstetrics 1995;49:125‐30. - PubMed
Mexico 2008 {published data only}
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Netherlands 2014 {published data only}
    1. EUCTR2014‐002524‐27‐NL. A randomized, placebo‐controlled, double blind, 4‐period, cross‐over trial, to study blood pressure lowering effects of losartan, Moxonidine and Low sodium diet in former pre‐eclamptic women ‐ PALM study. clinicaltrialsregister.eu/ctr‐search/search?query=eudract_number:2014‐00... (first received 18 December 2014).
Pakistan 1994 {published data only}
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Panama 2012 {published data only}
    1. Reyes OA, NCT01538875. Hydralazine vs. labetalol for the management of hypertensive crisis in patients with hypertensive disorders of pregnancy. a randomized controlled trial. clinicaltrials.gov/ct2/show/NCT01538875 (first received 24 February 2012).
Philippines 2000 {published data only}
    1. Decano MB, Cabrera LT. The effects of transdermal nitroglicerin (nitrol patch) on the uterine and umbilical artery blood flow in preeclampsia: a randomized double blind placebo controlled study. XVI Figo World Congress of Obstetric and Gynecology (Book 1); 2000 Sept 3‐8; Washington DC, USA. 2000:26.
Russia 1993 {published data only}
    1. Osadchaia OV, Nazarenko LG, Bobritskaia VV. The clinical and hemodynamic aspects of using peripheral vasodilators in hypertension in pregnant women [Klinicheskie i gemodinamicheskie aspekty primeneniia perifericheskikh vazodilatorov pri gipertenzii beremennykh]. Akusherstvo i Ginekologia 1993;1993(2):16‐20. - PubMed
Singapore 1996 {published data only}
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Singapore 1998 {published data only}
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Slovakia 2002 {published data only}
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South Africa 1988 {published data only}
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South Africa 1991b {published data only}
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South Africa 2004 {published data only}
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South Africa 2015 {published data only}
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South Africa 2016 {published data only}
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Sri Lanka 1994 {published data only}
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Uganda 1992 {unpublished data only}
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UK 1978 {published data only}
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UK 2015 {published data only}
    1. EUCTR2016‐005206‐19‐BE. Randomised controlled trial with pravastatin versus placebo for prevention of preeclampsia ‐ STATIN. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2016‐005206‐19‐BE (first received 7 June 2017).
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USA 1990b {unpublished data only}
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USA 1991 {published data only}
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Venezuela 1985 {published and unpublished data}
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Venezuela 1997 {published data only}
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Venezuela 2001 {published data only}
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Venezuela 2007 {published data only}
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References to ongoing studies

Canada 2006 {published data only}
    1. Smith G, ISRCTN45790835. Use of a nitric oxide (ISMN) for the prevention and management of pre‐eclampsia (pilot study). isrctn.com/ISRCTN45790835 (first received 29 November 2006).
Egypt 2017a {published data only}
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Egypt 2017b {published data only}
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Japan 2016a {published data only}
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Netherlands 2015 {published data only}
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USA 2014 {published data only}
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USA 2016a {published data only}
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USA 2017 {published data only}
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References to other published versions of this review

Abalos 2001
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