Table 2, Summary of the included studies - Evidence review for interventions for chronic hypertension

Table 2Summary of the included studies

Study	Participants/Diagnosis (and definition)	Intervention	Control	Outcomes
Askie 2007 Multicentre Individual participant data meta-analysis	N=3303 women with chronic hypertension No definition provided	Antiplatelet: predominantly aspirin (27 of the included studies), given in doses ranging from 50 to 150mg per day. 59% of women commenced treatment before 20 weeks’ gestation. 3 trials used aspirin with dipyridamole and 3 used different antiplatelet agents	No intervention: either placebo or no treatment	Pre-eclampsia
Atallah 1996 (ECPPA) Brazil RCT	N=473 women with chronic hypertension No definition provided	Aspirin: 60mg PO daily from 12 weeks’ gestation (or immediately following randomisation, if this was after 12 weeks) until delivery	No intervention: placebo tablets daily from 12 weeks’ gestation (or immediately following randomisation, if this was after 12 weeks) until delivery	Stillbirth and neonatal death Small-for-gestational age Preterm delivery (<37 weeks)^a Pre-eclampsia^a
Butters 1990 UK RCT	N=29 women with chronic hypertension sBP between 140 and 170mmHg and dBP between 90 and 110mmHg on 2 occasions separated by at least 24 hours	Atenolol: 50mg PO daily up to 200mg	No intervention: placebo tablets	Stillbirth Small-for-gestational age Birth weight Gestational age at delivery
Hamed 2014 Egypt and Saudi Arabia RCT	N=76 women with chronic hypertension sBP between 140 and 160mmHg and dBP between 90 and 110mmHg at least 6 hours apart in the first half of pregnancy	Induction of labour	Expectant management	Perinatal death Birth weight Gestational age at delivery Preterm birth Admission to neonatal unit Severe chronic hypertension Superimposed pre-eclampsia Placental abruption
Kasawara 2013 Brazil RCT	N=116 women with CHT (90.5%) or previous PE (9.5%) BP ≥ 140/90mmHg diagnosed before pregnancy or before 20 weeks’ gestation	Exercise (30 minutes per week riding a stationary bike)	No intervention	Birth weight (<2500; 2500 to 3999 and ≥4000g) Admission to neonatal unit Mode of birth
Magee 2015 South America, North America, Israel, Jordan, Oceania and Europe RCT	N=981 women with CHT (75.02%) or GH (24.98%) dBP ≥90mmHg before pregnancy or before 20⁺⁰ weeks’ gestation	Less-tight control (aiming for a target of dBP of 100mmHg)	Tight control (aiming for a target of dBP of 85mmHg)	Stillbirth Neonatal death up to 7 days Small-for-gestational age Birth weight Gestational age at delivery Admission to neonatal unit Severe hypertension HELLP Placental abruption Onset of labour Mode of birth
Moore 1982 UK RCT	N=72 women with CHT (65.2%) or PE (34.8%) BP ≥110/170mmHg on two separate occasions before 20 weeks’ gestational age	Labetalol: 100mg × 4 times/day	Methyldopa: 250 mg × 4 times/day	Stillbirth Neonatal death up to 7 days Small-for-gestational age Birth weight; gestational age at delivery Admission to neonatal unit Maximum sBP and dBP after entry Onset of labour Mode of birth
Moore 2015 USA RCT	N=186 women with chronic hypertension Defined as use of antihypertensive agent at baseline, or resting BP ≥ 140/90mmHg on two occasions at least four hours apart prior to pregnancy, or before 20 weeks’ gestation	Aspirin: 60mg PO once daily, started prior to 17 weeks’ gestation	No intervention: placebo tablets started prior to 17 weeks’ gestation	Small-for-gestational age Preterm delivery due to pre-eclampsia (<34 weeks)^a Pre-eclampsia^a
Parazzini 1993 Italy RCT	N=240 women with chronic hypertension or nephropathy Defined as diastolic BP 90 to 100mmHg or nephropathy with normal renal function and normal BP	Aspirin: 50mg PO once daily from randomisation (at 16 to 32 weeks) until delivery	No intervention	Small-for-gestational age^b
Poon 2017 Multicentre (UK, Spain, Italy, Belgium, Greece and Israel) RCT	N=110 women with chronic hypertension Study participants self-reported a diagnosis of chronic hypertension at the 11-13 week visit	Aspirin: 150mg PO once daily from randomisation (approximately 12-13 weeks) until 36 weeks’ gestation	No intervention: placebo tablet to be taken once daily from randomisation until 36 weeks’ gestation	Pre-eclampsia
Redman 1976, Cockburn 1982 UK RCT	N=208 women with CHT sBP >140 or dBP>90 on 2 occasions at least 24 hours apart before 28 weeks’ GA	Methyldopa: dose and administration route not reported	No intervention	Stillbirth Birth weight GA at delivery Impaired hearing Impaired vision
Sibai 1990 USA RCT	N=263 women with CHT Definition was not reported	Methyldopa: 750 mg/day up to 4g/day Labetalol: 300 mg/day increased up to 2400 mg/day.	No intervention	Perinatal death Small-for-gestational age Preterm birth Superimposed pre-eclampsia Placental abruption Mode of birth
van Vliet 2017 Multicentre Individual participant data meta-analysis	N=2518 women with chronic hypertension No definition provided	Antiplatelet: predominantly aspirin (15 of the included studies), given in doses ranging from 60 to 150mg per day. 1 trial used aspirin with dipyridamole and 1 used dipyridamole alone.	No intervention: either placebo or no treatment	Spontaneous preterm birth (<37 weeks, <34 weeks and <28 weeks)^b
Vigil-De Gracia 2014 Panama RCT	N=39 women with CHT BP >140/90 mmHg present before pregnancy or for first time before the 20th week of gestation	Amlodipine: 5mg/day PO	Aspirin: 75mg/day PO	Stillbirth Neonatal death Small-for-gestational age Birth weight Preterm birth Severe hypertension Placental abruption Mode of birth
Viinikka 1993 Finland RCT	N=208 women with chronic hypertension (89%) or severe pre-eclampsia in a previous pregnancy CHT defined as BP >140/90mmHg without treatment prior to pregnancy	Aspirin: 50mg aspirin/day PO	No intervention: placebo tablets to be taken daily PO	Perinatal mortality Small-for-gestational age Birth weight Gestational age Admission to neonatal unit Severe hypertension Superimposed pre-eclampsia Onset of labour
Webster 2017 UK RCT	N=114 women with CHT BP ≥140/90mmHg before 20 weeks’ gestation requiring antihypertensive treatment before 27^{+ 6} weeks’	Labetalol: 100 mg BID up to 1800 mg	Nifedipine: 10 mg BID up to 80 mg	Stillbirth Neonatal death Small-for-gestational age Birth weight Admission to neonatal unit Preterm birth GA at delivery Mode of delivery Superimposed PE Eclampsia Maternal death
Weitz 1987 US RCT	N=25 women with CHT BP ≥140/90 mmHg on 2 separate occasions at least 6 hours apart	Methyldopa: 250 mg PO TID	No intervention: one placebo tablet PO TID	Stillbirth Neonatal death up to 7 days GA at delivery Superimposed PE

: BID: twice a day; BP: blood pressure; CHT: chronic hypertension; dBP: diastolic blood pressure; GA: gestational age; GH: gestational hypertension; HELLP: haemolysis, elevated liver enzymes and low platelet count; mmHg: millimetres of mercury; N: total number of participants; PE: pre-eclampsia; PO: orally; sBP: systolic blood pressure; TID: three times a day
a: Data are included in individual participant data meta-analyses (by Askie 2007 or van Vliet 2017) therefore not analysed separately
b: Participants in this report are also included in the IPD by Askie 2007

From: Evidence review for interventions for chronic hypertension

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Evidence review for interventions for chronic hypertension: Hypertension in pregnancy: diagnosis and management: Evidence review A.

NICE Guideline, No. 133.

National Guideline Alliance (UK).

London: National Institute for Health and Care Excellence (NICE); 2019 Jun.

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