Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review -- Duley et al. 322 (7282): 329 Data Supplement

Characteristics of trials included in systematic review

Study identifier and main citation for included trials

Table Characteristics of trials included in systematic review

Study identifier (quality score)*	Methods	Participants	Interventions	Outcomes
Australia 1988^w1 (a)	Women given identification number at trial entry. Randomisation in pharmacy using a random number sequence linked to this number. Two groups: high umbilical artery systolic:diastolic ratio (>95th <99.5th centile) and umbilical artery systolic:diastolic ratio >99.5th centile. Data incomplete for second group, outcome only included if data for all women	46 women. Singleton pregnancy at 28-36 weeks and concern about fetal welfare. Umbilical artery velocity waveform systolic:diastolic ratio >95th centile Exclusions: diastolic pressure >110 mm Hg or >90 mm Hg with proteinuria, and maternal condition likely to lead to delivery	Aspirin 150 mg/day v placebo	Women: caesarean section, induction, placental weight
				Babies: stillbirth, neonatal death, ventilation, admission to SCBU, intraventricular haemorrhage, birth weight, gestation at delivery, head circumference, Apgar scores
Australia 1990^w2 (b)	Randomised trial; no other information. 1/21 women (5%) excluded as miscarriage at 20 weeks. Published as abstract only	21 women with renal disease. 20 had previous early onset pre-eclampsia	Dipyridamole (dose not known) + subcutameous heparin 15 000 u/day v no treatment	Women: hypertension, proteinuria, "complications"
				Babies: neonatal death
Australia 1995^w3 (b)	Instructions about the tablets in numbered sealed opaque envelopes. Women shown 5 envelopes and asked to choose 1	51 women at 28-36 weeks with ultrasound diagnosis of restricted fetal growth, umbilical artery Doppler systolic:diastolic ratio >95th centile. No previous aspirin during pregnancy	Aspirin 100 mg v starch tablets	Women: none
				Babies: mean gestation at delivery, small for gestational age (<3rd, <10th centile), 5 min Apgar score, admission to SCBU, intraventricular haemorrhage
Australia 1996^w4 (a)	Randomisation by taking the next in a series of numbered identical blister packs. 2 women withdrew, one from each group	104 women. Primiparous with abnormal uterine Doppler flow at 18 weeks (systolic:diastolic ratio >3.3 or systolic:diastolic >3 and early diastolic notch). Selected from 955 women screened, 186 with abnormal waveforms	Aspirin 100 mg /day v placebo	Women: pregnancy induced hypertension, pre-eclampsia, eclampsia, antepartum haemorrhage
				Babies: preterm birth, small for gestational age
Australia 1997^w5 ©	Allocated by a series of random numbers. 10% (12/120) of women excluded as withdrew before starting treatment	120 women with one of: pre-existing hypertension (³140/90 mm Hg before pregnancy on ³2 occasions or antihypertensive therapy), renal disease, previous early severe pre-eclampsia Exclusions: aspirin allergy, aspirin-sensitive asthma, pre-existing bleeding diathesis, or multiple pregnancy	Aspirin 100 mg modified release daily from 17-19 weeks until delivery v placebo	Women: proteinuria, duration of pregnancy, indications delivery, caesarean section, maximum antenatal blood pressure, "complications"
				Babies: perinatal death, birth weight, Apgar scores
Austria 1992^w6 (a)	Randomised by coded packages of medication; assessment of primary outcome blinded	41 women. Primigravidas with positive roll over test (increase of 20 mm Hg in diastolic pressure) at 28-32 weeks Exclusions: existing hypertension, renal gut lung or heart disease, intrauterine growth retardation, impending preterm birth	Aspirin 80 mg/day until 37 weeks v placebo	Women: pregnancy induced hypertension, pre-eclampsia, caesarean section, preterm birth (<37 weeks),
				Babies: stillbirths, neonatal death, small for gestational age (<10th centile), neonatal bleeding, admission to SCBU
Barbados 1998^w7 (a)	Single centre, treatment packs randomly numbered by computer in clinic and dispensed by pharmacist. 55/3697 women (1.5%) excluded after randomisation: 42 pack labelling errors, 8 women not pregnant and 6 lost to follow up.	3697 women at 12-32 weeks gestation Exclusions: increased risk of bleeding, aspirin allergy, high likelihood of immediate delivery, or previous placental abruption	Aspirin 75 mg controlled release daily until delivery v placebo	Women: pre-eclampsia, antepartum haemorrhage, postpartum haemorrhage, caesarean section, duration of pregnancy, use of antihypertensive and anticonvulsant drugs
				Babies: stillbirth, death before hospital discharge, days in SCBU, bleeding problems, birth weight
Brazil 1996^w8 (a)	Central telephone randomisation; 39/1009 women (4%) lost to follow up. Conducted in 12 university teaching hospitals and 182 obstetric offices	1009 women at 12-32 weeks gestation (41% £20 weeks) at risk of pre-eclampsia: generally low/moderate risk (47% primiparous, 47% chronic hypertension, 6% diabetes). Exclusions: bleeding risk, asthma, allergy to aspirin, gastric ulcer, placenta praevia	Aspirin 60 mg/day v placebo	Women: pre-eclampsia, caesarean section, antepartum haemorrhage
				Babies: small for gestational age, perinatal death, preterm birth, neonatal bleeding
China 1996^w9 (b)	Prospective randomised double-blind study	84 women with singleton pregnancy at high risk of intrauterine growth retardation at 28-32 weeks gestation	Aspirin 75 mg daily from 28-34 weeks for 6-8 weeks v placebo	Women: pregnancy induced hypertension, caesarean section, preterm delivery.
				Babies: neonatal death, intrauterine growth retardation, intraventricular haemorrhage
China 1999^w10 (b)	Randomisation by offering woman 5 sealed envelopes (2 aspirin, 2 calcium, 1 placebo). 132 women allocated aspirin, 154 calcium, and 83 control. Calcium group excluded from this review. 22 women lost to follow up (14 aspirin, 8 control)	215 primigravid women with mean arterial pressure >80 mm Hg and <106 mm Hg early in second trimester and >60 mm Hg at 22-24 weeks	Aspirin 80 mg /day until delivery v control, no placebo mentioned	Women: pregnancy induced hypertension, pre-eclampsia, eclampsia, caesarean section.
				Babies: gestation at delivery (mean), birth weight, Apgar scores
CLASP 1994^w11 (a)	By telephoning central computerised randomisation service. 0.6% (55/9364) lost to follow up. International study. Compliance: 96% started treatment, 88% took it ³80% of time from entry-delivery. Follow up of surviving children with GP letter at 12 months in UK (4688 with 4675 alive at 12 months) and parental questionnaire at 18 months in UK and Canada (410 with 407 alive at 18 months). For GP letter, 89% response, for parental questionnaire 86% response	9364 women at 12-32 weeks gestation at risk of pre-eclampsia or intrauterine growth retardation or women with established pre-eclampsia or intrauterine growth retardation. Only 7974 women randomised for prevention included in review	Aspirin 60 mg daily until delivery v placebo	Women: Death, eclampsia, pre-eclampsia, bleeding complications, caesarean section, induction, problems with epidural, postpartum haemorrhage, transfusion, use of antihypertensive or anticonvulsant drugs, compliance
				Babies: death (stillbirth, neonatal, one year), small for gestational age (<3rd centile), gestation at delivery, admission to SCBU, intraventricular haemorrhage, other neonatal bleeding. At 12-18 months: developmental delay, congenital malformations, respiratory problems, hospital admissions
Colorado 1993^w12 (b)	RandomisedCno further information; completeness of follow up unclear. Multicentre trial, stopped early due to slow recruitment	100 nulliparous women with multiple pregnancy in early pregnancy	Aspirin 81 mg/day v placebo	Women: pregnancy induced hypertension, pre-eclampsia
				Babies: none reported
EPREDA 1991^w13 (b)	Randomised by centre with stratification for one or two previous poor outcomes. 1 woman excluded after randomisation. Two studies within the report. Only data for placebo study included in review.	323 women at 15-18 weeks gestation with poor outcome in previous 2 pregnancies, at least 1 being intrauterine growth retardation or intrauterine growth retardation in previous pregnancy.	Aspirin 150 mg /day, or aspirin 150 mg + dipyridamole 225 mg/day v placebo	Women: death, diastolic pressure >90 mm Hg, proteinuria, abruption, caesarean section <34 weeks, "poor outcome"
		Exclusions: twins, uterine malformation, renal disease, secondary hypertension, diabetes, cardiac disease	Aspirin 150 mg + dypridamole 225 mg/day v aspirin 150 mg/day	Babies: stillbirth, neonatal death, ventilation, admission to SCBU, small for gestational age (<10th centile), duration of hospital stay (mean)
Finland 1993^w14 (b)	Sealed envelopes, no further details. 3 centres. 5.3% (11/208) women excluded: 6 from aspirin group (1 miscarriage, 1 anencephaly, 4 discontinued due to urticaria, raised aspartate transaminase or prolonged bleeding time), 5 from placebo group (1 miscarriage, 3 raised aspartate transaminase or prolonged bleeding time, 1 lost to follow up)	208 women with pre-existing hypertension (>140/90 mm Hg before pregnancy) or previous severe pre-eclampsia (in immediately preceding pregnancy), and 12-18 weeks gestation Excluded: women proteinuric before pregnancy	Aspirin 50 mg/day v placebo	Women: exacerbation of hypertension +/- proteinuria, caesarean section, blood loss at delivery (mean), hospital admission during pregnancy, bleeding time and diastolic pressure at 36 weeks
				Babies: perinatal death, admission to SCBU, birth weight, small for gestational age, gestation at delivery
Finland 1997^w15 (b)	Randomised–no other information	26 high risk women with uterine artery bilateral notches on Doppler, at 22-24 weeks.	Aspirin 50 mg v no treatment	Women: pregnancy induced hypertension, pre-eclampsia, abruption, delivery <37 weeks
				Babies: stillbirth, intrauterine growth retardation (<10th centile), intraventricular haemorrhage on ultrasonography, gestation at delivery (mean), birth weight
France 1985^w16 (b)	Randomly allocated to group A or B–no other information. 9% (9/102) excluded from analysis (2 controls lost to follow up, 4 treatment and 3 controls had miscarriage <16 weeks).	102 women at high risk of pre-eclampsia or intrauterine growth retardation Exclusions: secondary hypertension, or known or suspected renal disease.	Aspirin 150 mg + dipyridamole 300 mg daily, from 3 months until delivery v no treatment	Women: pregnancy induced hypertension (³140/85 mm Hg), pre-eclampsia, caesarean section, abnormal bleeding during delivery or caesarean section, abruption, headache
				Babies: stillbirth, neonatal death, fetal malformation, small for gestational age (<10th <3rd centile, live births only), haemorrhagic complication (undefined)
France 1990^w17 (b)	Randomised study–no other information. Published in abstract form only	91 women at high risk of pregnancy induced hypertension because of previous early onset pre-eclampsia, severe intrauterine growth retardation, or fetal death due to placental insufficiency	Aspirin 100 mg + dipyridamole 300 mg daily until delivery v no antiplatelet	Women: pregnancy induced hypertension , duration of pregnancy (mean)
				Babies: fetal death, birth weight
Israel 1989^w18 (b)	Coded packages of 100 pills allocated according to a computer-generated randomisation list	65 women with either twin pregnancy, history of pre-eclampsia in first pregnancy, and a positive rollover test at 28-29 weeks gestation	Aspirin 100 mg daily v placebo	Women: pregnancy induced hypertension, pre-eclampsia, caesarean section, days in hospital (mean)
				Babies: stillbirth, neonatal death, gestation at birth (mean), preterm (<37 weeks), small for gestational age (<10th centile), Apgar score, ventilation, admission to SCBU, intraventricular haemorrhage, haematuria, sepsis work up
Israel 1994^w19 (b)	Allocated to a coded package according to randomisation list. 1 women withdrawn from placebo group due to thrombocytopenia– outcomes included where possible	48 women with twin pregnancies at about 18 weeks	Aspirin 100 mg/day v placebo	Women: pregnancy induced hypertension, pre-eclampsia, caesarean section, intrauterine growth retardation
				Babies: preterm birth, perinatal mortality, birth weight discordancy
Italy 1989^w20 (b)	Randomly assigned–no other information given	33 women at risk of hypertension because of essential hypertension or previous obstetric history (placental insufficiency causing fetal death, severe intrauterine growth retardation, or pre-eclampsia <32 weeks) Excluded if antiphospholipid antibodies present	Aspirin 60 mg/day from 12 weeks until delivery v placebo	Women: pregnancy induced hypertension (>140/90 mm Hg and previously normal)
				Babies: perinatal death, assisted ventilation, haemorrhagic complications, birth weight <10th centile, preterm (<37 weeks), Apgar scores, respiratory distress syndrome
Italy 1993^w21 (a)	Allocation by a telephone call to one of two randomisation centres. 5.8% (64/1106) of women lost to follow up (18/523 aspirin, 46/583 control). Follow up: postal questionnaire for 1083 children at 18 months (excludes 41 born before follow up started). 427 aspirin responders (72%) and 361 no treatment (73%). Data not presented separately for prophylaxis and treatment, all women included in this review	1106 women at 16-32 weeks gestation. Prophylactic: age <18 or >40 years, mild-moderate chronic hypertension, nephropathy with normal renal function and blood pressure, pregnancy induced hypertension or intrauterine growth retardation in previous pregnancy, twins. Therapeutic: pregnancy induced hypertension (diastolic pressure 90-110 mm Hg) or early intrauterine growth retardation (fetal abdominal circumference ³2 SD below mean for gestational age) Excluded: Chronic disease, allergy to aspirin, fetal malformation	Aspirin 50 mg/day v no treatment	Women: pregnancy induced hypertension +/- proteinuria, abruption, induced or spontaneous abortion, caesarean section
				Babies: Perinatal mortality, gestation at delivery, birth weight <5th centile, admission to SCBU, intraventricular haemorrhage, gastric bleed. At 18 months: death, malformations, height and weight <10th centile, and respiratory, motor, sight, hearing or language problems
Italy 1999^w22 (b)	Randomised. 9 women stopped treatment early (4 aspirin, 5 placebo)	216 women aged 18-36, pre-existing hypertension or previous severe pre-eclampsia at 12-26 weeks	Aspirin 50 mg/day v placebo
Jamaica 1998^w23 (a)	Women given sequential numbers on admission which identified a bottle containing either aspirin or placebo. 179/6275 (3%) lost to follow up. 50 women with multiple pregnancy excluded. Some women entered twice, but numbers not given	6275 primiparous women <32 weeks and no contraindication to aspirin. 144 aspirin women and 161 placebo randomised after 32 weeks but included in analysis	Aspirin 60 mg/day until delivery v placebo	Women: Hypertension (diastolic ³90 mm Hg or systolic ³140 mmHg or rise of 25 mm Hg diastolic or 40 mm Hg systolic), pre-eclampsia, eclampsia, caesarean section, antenatal admission, postpartum haemorrhage
				Baby: perinatal death, preterm delivery, birth weight <2500 g, admission to SCBU, 5 min Apgar <5, intraventricular haemorrhage, other neonatal bleeding
Japan 1999^w24 (b)	Enrolled randomly–no further information	40 women with severe pre-eclampsia in previous pregnancy. Enrolled at 6-18 weeks, treatment started at 20 weeks	Ozagrel hydrochloride (thromboxane synthetase inhibitor) 400 mg/day from 20 weeks–delivery v placebo	Women: pre-eclampsia
				Babies: Preterm delivery, delivery <32 weeks, small for gestational age
Netherlands 1986^w25 (b)	Coded packages, allocated according to a randomisation list. 2 women in treatment group excluded because of non-compliance, but data for some clinical outcomes reported	46 angiotensin II sensitive primigravid women at 28 weeks gestation with uncomplicated pregnancies, no history of hypertension, cardiovascular or renal disease, diastolic pressure <80 mm Hg, and taking no drugs except iron	Aspirin 60 mg/day v placebo	Women: eclampsia, pregnancy induced hypertension (diastolic pressure ³95 mm Hg on two or more occasions 6 hours apart), pre-eclampsia (hypertension as above plus proteinuria >0.5 g/l), preterm delivery (<37 weeks), caesarean section
				Babies: stillbirth, neonatal death, respiratory distress syndrome, small for gestational age (<10th, <3rd centile)
Netherlands 1989^w26 (b)	Coded packages containing trial drug allocated according to a randomisation list	10 primigravid women with chronic hypertension and a positive angiotensin II sensitivity test at 26 weeks. No proteinuria, diastolic pressure <90 mm Hg, serum creatinine <70 mmol/l, and fetus adequately grown	Aspirin 60 mg v placebo	Women: pregnancy induced hypertension (diastolic increase ³20 mm Hg), pre-eclampsia (hypertension as before plus proteinuria ³500 mg/l), caesarean section
				Babies: small for gestational age (<10th centile)
Netherlands 1991^w27 (b)	Coded packages allocated according to randomisation sheet. Code broken at 34 weeks, some women then started aspirin	36 women with a positive angiotensin II sensitivity test at 28 weeks	Aspirin 60 mg/day from 28-32 weeks v placebo	Women: hypertension at 34 weeks
				Babies: stillbirth
South Africa 1988^w28 (b)	By computer generated random numbers, no other information. One woman lost to follow up. Published only as abstract	44 women with elevated mid-trimester blood pressure, 12-28 weeks gestation, diastolic pressure 80-105 mm Hg, and otherwise normal	aspirin 81 mg/day or aspirin 81 mg + dipyridamole 200 mg/day v no antiplatelet drug	Women: pre-eclampsia
				Babies: stillbirth
Tanzania 1995^w29 (b)	Coded packages, A and B. No other information	127 women with a positive roll over test Exclusions: hypertension or increased blood pressure before screening, proteinuria >300 mg	Aspirin 80 mg/day v placebo	Women: pregnancy induced hypertension, pre-eclampsia
				Babies: none
Thailand 1996†^w30 ^(a)	Identical treatment and placebo tablets (22 weeks supply) in identical containers (100 per box)–patient chose a container at random. Compliance testing: 86% aspirin, 81% placebo. 10% lost after randomisation (aspirin: 106 returned home, 1 rubella, 2 rashes. Placebo: 38 returned home, 1 twin, 1 abortion, 1 HIV, 1 fetal abnormality, 1 stillbirth)	1500 low risk nulliparous women at 18-22 weeks, ultrasonography to confirm dates (mean at randomisation 20.7 weeks) Exclusions: renal or cardiovascular disease, diabetes, twins, hypertension	Aspirin 60 mg/day, until birth v placebo	Women: Death, pregnancy induced hypertension, pre-eclampsia, eclampsia, caesarean section, antepartum haemorrhage
				Babies: stillbirth, preterm birth, small for gestational age
UK 1990^w31 (a)	Computer generated randomisation list. Serially numbered bottles dispensed by pharmacist. 5.7% (6/106) excluded after randomisation (5 women moved house, 1 withdrew after 3 weeks)	106 primigravid women with persistently abnormal Doppler waveform studies at 24 weeks	Aspirin 75 mg/day v placebo	Women: pregnancy induced hypertension, proteinuria, hypertension <37 weeks gestation, caesarean section for hypertension
		Exclusions: Aspirin allergy, diabetes, bleeding disorders, peptic ulceration, systemic lupus erythematosus		Babies: perinatal death, small for gestational age (<5th centile)
UK 1992^w32 (b)	Simply randomised with block size four	18 normal primigravid women, 16 weeks gestation, and 16 primigravid women with pregnancy induced hypertension but no proteinuria at >20 weeks	Aspirin 60 mg/day until delivery v placebo	Women: duration of labour, blood loss at delivery
				Babies: <36 weeks at delivery, small for gestational age (<10th centile), minor bruising
UK 1992b^w33 (b)	Randomly allocated–no other information.	26 women with history of recurrent miscarriage or connective tissue disorder and positive for anticardiolipin antibodies	Aspirin 75 mg/day v no treatment	Women: miscarriage
				Babies: neonatal death
UK 1995^w34 (b)	Computer generated randomisation list used to produce sealed envelopes. 4/122 women (3%) withdrew after randomisation	122 women with no previous pregnancy proceeding beyond 12 weeks, haemoglobin >132 g/l at 12-19 weeks gestation, diastolic pressure <90 mm Hg, and no proteinuria Exclusions: multiple pregnancy, diabetes, recurrent miscarriage, or contraindication to aspirin	Aspirin 75 mg from 18 weeks until delivery v placebo.	Women: pregnancy induced hypertension, pre-eclampsia, eclampsia, abruption, caesarean section, induction of labour, side effects
				Babies: perinatal mortality, delivery <34 weeks gestation, admission to SCBU, small for gestational age (<5th centile)
USA 1993^w35 (a)	Efforts were made to conceal randomisation; placebo controlled; <1% lost to follow up	604 primiparous women in single antenatal clinic Exclusions: renal or collagen disease, diabetes, essential hypertension, multiple pregnancy	Aspirin 60 mg/day, from 22 weeks v placebo	Women: pregnancy induced hypertension, pre-eclampsia, eclampsia, antepartum haemorrhage, Caesarean section, preterm delivery (<37, <34, <32 weeks)
				Babies: perinatal death, small for gestational age
USA 1993a^w36 (b)	Assigned randomly–no further details. 150/3135 (4.8%) lost to follow up: 85 from aspirin group and 65 from placebo.	3135 nulliparous women at 13-25 weeks with blood pressure <135/85 mm Hg and no proteinuria; out of the 4241 entered into a run-in compliance phase Exclusions: chronic hypertension, diabetes, renal disease, other medical illness	Aspirin 60 mg/day v placebo.	Women: pregnancy induced hypertension, pre-eclampsia, eclampsia, caesarean section, abruption, preterm delivery, postpartum haemorrhage.
				Babies: stillbirths, neonatal deaths, small for gestational age (<10th centile), bleeding
USA 1994^w37 (b)	Randomised, no further details. 5/54 (9%) women lost to follow up. Published as abstract only	54 women with chronic hypertension or previous severe pre-eclampsia, enrolled at 13-15 weeks	Aspirin 100 mg sustained release/day until 37 weeks v placebo	Women: pre-eclampsia
				Babies: Stillbirth, small for gestational age
USA 1998†^w38 ^(a)	Packets prepared using computer generated random numbers. Opened consecutively in each centre. Multicentre study. 36/2539 women (1%) lost to follow up	2539 women 13-26 weeks gestation with insulin treated diabetes, chronic hypertension, multiple pregnancy, or pre-eclampsia in previous pregnancy Exclusions: Women with multiple pregnancy, if also diabetes, chronic hypertension, or proteinuria	Aspirin 60 mg/day v placebo	Women: pregnancy induced hypertension, pre-eclampsia, abruption, preterm delivery, postpartum haemorrhage
				Baby: death, intrauterine growth retardation (<10th centile), intraventricular haemorrhage, other neonatal bleeding
Zimbabwe 1998^w39 (a)	Randomisation list used to determine sequence of numbered containers. 20/250 (8%) women lost to follow up	250 women at 20-28 weeks and pre-eclampsia in previous pregnancy, especially if <32 weeks, or chronic hypertension Exclusions: aspirin hypersensitivity, pre-eclampsia, bleeding, or peptic disorder	Aspirin 75 mg/day v placebo	Women: pre-eclampsia, antihypertensive drug, preterm delivery, postpartum haemorrhage, caesarean section
				Babies: death, Intrauterine growth retardation, admission to SCBU

*Score for quality of concealment of allocation: a=adequate, b=unclear, c=inadequate.

†Additional data provided by the authors.

SCBU=special care baby unit.

Study identifier and main citation for included trials

Australia 1988 Trudinger BJ, Cook CM, Thompson RS, Giles WB, Connelly AJ. Low-dose aspirin improves fetal weight in umbilical placental insufficiency. Lancet 1988;ii:214-5.
Australia 1990 North RA, Fairley KF, Kloss M, Ihle B, Kincaid-Smith P. Prevention of pre- eclampsia in women with renal disease. Proceedings of 7th world congress of hypertension in pregnancy, 1990; Perugia, Italy, 1990:75.
Australia 1995 Newnham JP, Godfrey M, Walters BJN, Philips J, Evans SF. Low dose aspirin for the treatment of fetal growth restriction: a randomised controlled trial. Aust NZ J Obstet Gynaecol 1995;35:370-4.
Australia 1996 Morris JM, Fay RA, Ellwood DA, Cook C, Devonald KJ. A randomized controlled trial of aspirin in patients with abnormal uterine artery blood flow. Obstet Gynecol 1996;87:74-8.
Australia 1997 Gallery EDM, Ross MR, Hawkins M, Leslie GI, Gyory AZ. Low-dose aspirin in high-risk pregnancy. Hyper Preg 1997;16:229-38.
Austria 1992 Schrocksnadel H, Sitte B, Alge A, Stechel-Berger G, Schwegel P, Pastner E, et al. Low-dose aspirin in primigravidae with positive roll-over test. Gynecol Obstet Invest 1992;34:146-50.
Barbados 1998 Rotchell YE, Cruickshank JK, Phillips Gay M, Griffiths J, Stuart A, Farrell B, et al. Barbados low dose aspirin study in pregnancy (BLASP): a randomized controlled trial for the prevention of pre-eclampsia and its complications. Br J Obstet Gynaecol 1998;105:286-92.
Brazil 1996 ECPPA: randomised trial of low dose aspirin for the prevention of maternal and fetal complications in high risk pregnancies. Br J Obstet Gynaecol 1996;103:39-47.
China 1996 Wang Z, Li W. A prospective randomized placebo-controlled trial of low dose aspirin for prevention of intra uterine growth retardation. Chin Med J 1996;109:238-42.
China 1999 Rogers MS, Fung HYM, Hung CY. Calcium and low-dose aspirin prophylaxis in women at high risk of pregnancy- induced hypertension. Hyper Preg 1999;18:165-72.
CLASP 1994 CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet 1994;343:619-29.
Colorado 1993 Porreco RP, Hickok DE, Williams MA, Krenning C. Low-dose aspirin and hypertension in pregnancy. Lancet 1993;341:312.
EPREDA 1991 Uzan S, Beaufils M, Breart G, Bazin B, Capitant C, Paris J. Prevention of fetal growth retardation with low-dose aspirin: findings of the EPREDA trial. Lancet 1991;337:1427-31.
Finland 1993 Viinikka L, Hartikainen-Sorri AL, Lumme R, Hiilesmaa V, Ylikorkala O. Low dose aspirin in hypertensive pregnant women: effect on pregnancy outcome and prostacyclin-thromboxane balance in mother and newborn. Br J Obstet Gynaecol 1993;100:809-15.
Finland 1997 Zimmerman P, Eirio V, Koskinen J, Niemi K, Nyman R, Kujansuu E, et al. Effect of low dose aspirin treatment on vascular resistance in the uterine, uteroplacental, renal and umbilical arteries. A prospective longitudinal study on a high risk population with persistent notch in the uterine arteries. Eur J Ultrasound 1997;5:17-30.
France 1985 Beaufils M, Uzan S, Donsimoni R, Colau JC. Prevention of pre-eclampsia by early antiplatelet therapy. Lancet 1985;i:840-2.
France 1990 Azar R, Turpin D. Effect of antiplatelet therapy in women at high risk for pregnancy-induced hypertension. Proceedings of 7th world congress of hypertension in pregnancy, 1990; Perugia, Italy, 1990:257.
Israel 1989 Schiff E, Peleg E, Goldenberg M, Rosenthal T, Ruppin E, Tamarkin M et al. The use of aspirin to prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in relatively high risk pregnancies. N Engl J Med 1989;321:351-6.
Israel 1994 Caspi E, Raziel A, Sherman D, Arieli S, Bukovski I, Weintraub Z. Prevention of pregnancy induced hypertension in twins by early administration of low-dose aspirin: A preliminary report. Am J Reprod Immunol 1994;31:19-24.
Italy 1989 Benigni A, Gregorini G, Frusca T, Chiabrando C, Ballerini S, Valcamonico A, et al. Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension. N Engl J Med 1989;321:357-62.
Italy 1993 Italian Study of Aspirin in Pregnancy. Low-dose aspirin in prevention and treatment of intrauterine growth retardation and pregnancy-induced hypertension. Lancet 1993;341:396-400.
Italy 1999 Volpicelli T, D'Anto V, Faticato A, Galante L, Civitillo RM, Rappa C, et al. Trial prospettico sull'uso profilattico dell'aspirina in donne gravide ad alto rischio di preeclampsia. Gestosi 1999:159-60.
Jamaica 1998 Golding J. A randomised trial of low dose aspirin for primiparae in pregnancy. Br J Obstet Gynaecol 1998;105:293-9.
Japan 1999 Seki H, Kuromaki K, Takeda S, Kinoshita K, Satoh K. Trial of prophylactic administration of TXA2 synthetase inhibitor, ozagrel hydrochloride, for preeclampsia. Hyper Preg 1999;18:157-64.
Netherlands 1986 Wallenburg HCS, Dekker GA, Makovitz JW, Rotmans P. Low-dose aspirin prevents pregnancy-induced hypertension and pre-eclampsia in angiotensin-sensitive primigravidae. Lancet 1986;i:1-3.
Netherlands 1989 Dekker GA. Prediction and prevention of pregnancy-induced hypertensive disorders: a clinical and pathophysiologic study [[MD thesis]]. Rotterdam: University Medical School, 1989: pp150.
Netherlands 1991 Wallenburg HCS, Dekker GA, Makovitz JW, Rotmans N. Effect of low-dose aspirin on vascular refractoriness in angiotensin-sensitive primigravid women. Am J Obstet Gynecol 1991;164:1169-73.
South Africa 1988 Railton A, Davey A. Aspirin and dypyridamole in the prevention of pre-eclampsia: effect on plasma prostanoids 6 keto PG1a and TXB2 and clinical outcome of pregnancy. Proceedings of the 6th world congress of the International Society for the Study of Hypertension in Pregnancy, 1988 May 22-26; Montreal, Quebec, Canada, 1988:60.
Tanzania 1995 Ramaiya C, Mgaya HN. Low dose aspirin in prevention of pregnancy-induced hypertension in primigravidae at the Muhimbili Medical Centre, Dar es Salaam. East Afr Med J 1995;72:690-3.
Thailand 1996 Herabutya Y, Jetsawangsri T, Saropala N. The use of low-dose aspirin to prevent preeclampsia. Int J Gynecol Obstet 1996;54:177.
UK 1990 McParland, Pearce JM, Chamberlain GVP. Doppler ultrasound and aspirin in recognition and prevention of pregnancy-induced hypertension. Lancet 1990;335:1552-5.
UK 1992 Louden KA, Broughton Pipkin F, Symonds EM, Tuohy P, O'Callaghan C, Heptinstall S, et al. A randomized placebo-controlled study of the effect of low dose aspirin on platelet reactivity and serum thromboxane B2 production in non-pregnant women, in normal pregnancy, and in gestational hypertension. Br J Obstet Gynaecol 1992;99:371-6.
UK 1992b Quenby S, Farquharson R, Ramsden G. The obstetric outcome of patients with positive anticardiolipin antibodies: aspirin vs no treatment. Proceedings of 26th British congress of obstetrics and gynaecology, 1992; Manchester, U.K, 1992:443.
UK 1995 Davies NJ, Gazvani MR, Farquharson RG, Walkinshaw SA. Low-dose aspirin in the prevention of hypertensive disorders of pregnancy in relatively low-risk nulliparous women. Hyper Preg 1995;14:49-55.
USA 1993 Hauth JC, Goldenberg RL, Parker CR Jr, Philips JB 3rd, Copper RL, DuBard MB, et al. Low-dose aspirin therapy to prevent preeclampsia. Am J Obstet Gynecol 1993;168:1083-91.
USA 1993a Sibai BM, Caritis SN, Thom E, Klebanoff M, McNellis D, Rocco L, et al. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. N Engl J Med 1993;329:1213-8.
USA 1994 August P, Helseth G, Edersheim TG, Hutson JM, Druzin M. Sustained release, low-dose aspirin ameliorates but does not prevent preeclampsia (PE) in a high risk population. Proceedings of 9th international congress, International Society for the Study of Hypertension in Pregnancy; 1994; Sydney, Australia, 1994:72.
USA 1998 Caritis S, Sibai B, Hauth J, Lindheimer M, Klebanoff M, Thom E, et al. Low -dose aspirin to prevent preeclampsia in women at high risk. N Eng J Med 1998;338:701-5.
Zimbabwe 1998 Byaruhanga RN, Chipato T, Rusakaniko S. A randomized controlled trial of low-dose aspirin in women at risk from pre-eclampsia. Int J Gynaecol Obstet 1998;60:129-35.

Main citation for excluded studies

Robinson JS. Can the genetic risk of pre-eclampsia be reduced by low dose aspirin? Personal communication, March 25 1993.
Trudinger BJ, Cook CM, Giles WB, Connelly AJ, Thompson RS. Low-dose aspirin and twin pregnancy. Lancet 1989;ii:1214.
Michael CA, Seville P, Wadeisha P, Walters BNJ. Randomised double blind placebo controlled trial of aspirin in the prevention of pre-eclampsia. Proceedings of 7th world congress of hypertension in pregnancy, 1990; Perugia, Italy, 1990:73.
Ferrier C, North R, Kincaid-Smith P. Low dose aspirin delays the onset of pre-eclampsia in pregnancies with abnormal uteroplacental circulation. Proceedings of the 10th World Congress of the International Society for the Study of Hypertension in Pregnancy; 1996 August 4-8; Seattle, Washington, USA, 1996:151.
Montenegro CAB. The effect of aspirin therapy on the uterine circulation in reeclampsia. Proceedings of the 8th World Congress of the International Society for the Study of Hypertension in Pregnancy; 1992 November 8-12; Buenos Aires, 1992:66.
Cheng WW, Zhang ZJ. Low-dose aspirin preventing pregnancy induced hypertension [[In Chinese]]. Chung Hua Fu Chan Ko Tsa Chih 1991;26(6):342-5.
Hernandez F, Martinez MF, Camero A, Pinzon JA. Low dose aspirin as prophylactic therapy of pregnancy induced hypertension. Revista Colombiana de Obstetricia y Ginecologia 1996;47:197-201.
Peterseim H, Hofmann KD, Wagner F, Peterseim S, Meier P. Inhibition of prostaglandin synthetase by low-dose acetylsalicylic acid - effects on severity of pregnancy induced hypertension and fetal outcome. Proceedings of 10th European Congress of Perinatal Medicine; 1986; Leipzig, Germany, 1986:290.
Heinrich J. Prophylactic management of pregnancy induced hypertension (PIH). Proceedings of 11th European Congress of Perinatal Medicine; 1988; Rome, Italy, 1988:274.
Toppozada M, Darwish EA, Osman YF, Abd-Rabbo MS. Low dose acetyl salicylic acid in severe pre-eclampsia. Int J Gynecol Obstet 1991;35:311-7.
Kaaja R, Julkunen H, Viinikka L, Ylikorkala O. Production of prostacyclin and thromboxane in lupus pregnacies: effect of small dose of aspirin. Obstet Gynecol 1993;81:327-31.
Niedner W, Beller FK. The influence of ASA on pre-eclampsia. Proceedings of the International Society for the Study of Hypertension in Pregnancy; 1986; Nottingham, UK, 1986:101.
Grab D, Erdmann M, Paulus W, Oberhoffer R, Lang D. Effects of low dose aspirin on uterine and fetal blood flow during pregnancy: a randomized placebo controlled double blind trial. Acta Obstet Gynecol Scand 1997;76:38.
Erdmann M, Paulus WE, Flock F, Herget I, Terinde R, Grab D. Utero-und fetoplazentae haemodynamische Messiungen unter low-dose aspirin [Haemodynamic measurements of the utero and fetoplacental circulation during low-dose aspirin treatment]. Z Geburtsh Neonatol 1999;203:18-23.
Grover V, Sachdeva S, Kumari S. Evaluation of dipyridamole and aspirin in prevention and management of intrauterine growth retardation. J Perinat Med 1991;19:104.
Regi A. Randomised controlled trial of low dose aspirin in high risk pregnancy. Personal communication of unpublished study.
Tewari S, Kaushish R, Sharma S, Gulati N. Role of low dose aspirin in prevention of pregnancy induced hypertension. J Indian Med Assoc 1997;95:43-5, 47.
Regan CL, McAdam BF, McParland P, Boylan PC, FitzGerald GA, Fitzgerald DJ. Reduced fetal exposure to aspirin using a novel controlled release preparation in normotensive and hypertensive pregnancies. Br J Obstet Gynaecol 1998;105:732-8.
Capetta P, Airoldi ML, Tasca A, Bertulessi C, Rossi E, Polvani F. Prevention of pre-eclampsia and placental insufficiency. Lancet 1986;1:919.
Wallenburg HCS, Rotmans N, Noort WA, Keirse MJNC. Effect of low-dose aspirin with and without dipyridamole on prevention of recurrent idiopathic fetal growth retardation. Proceedings of 2nd European Congress on Prostaglandins in Reproduction; 1991; The Hague, Netherlands, 1991:92.
Kraayenbrink AA, Robson M, Dekker GA, Pearce JM, van Geijn HP. Prevention of preeclampsia and fetal growth retardation; allylestrenol vs aspirin, a two centered study. Proceedings of 9th International Congress, International Society for the Study of Hypertension in Pregnancy; 1994; Sydney, Australia, 1994:125.
Hutton JD, Wilkinson AM. Poor participation of nulliparous women in a low dose aspirin study to prevent preeclampsia. NZ Med J 1990;103:511-2.
McCowan LME, Harding J, Roberts A, Barker S, Ford C, Stewart A. Administration of low dose aspirin to mothers with small for gestational age fetuses and abnormal umbilical Doppler studies to increase birthweight: a randomised double-blind controlled trial. Br J Obstet Gynaecol 1999;106:647-51.
Gilani A, Khan Z. Role of aspirin in management of pregnancy induced hypertension. A study in Pakistani population. Specialist 1994;10:323-5.
Uzan S, Beaufils M, Bazin B, Danays T. Idiopathic recurrent fetal growth retardation and aspirin-dipyridamole therapy [letter]. Am J Obstet Gynaecol 1989;160:763-4.
Rogov VA, Tareeva I, Sidorova S, Androsova SO, Katamadze KT, Nikiforova OV. Prevention of pregnancy complications in glomerulonephritis and hypertension with acetylsalicylic acid and curantyl (translation). Ter Arkh 1993;65:65-8.
Sajina-Stritar B, Novak-Antolic Z. Antiaggregational therapy in preventing EPH gestosis and its complications. J Perinat Med 1992;20(Suppl 1):73.
Sajina-Stritar B. Prevention of gestational hypertension and its comlications with ASA and N-3 fatty acids (comparative study). Proceedings of 14th European Congress of Perinatal Medicine; 1994; Helsinki, Finland, 1994:182.
Richards A, Moodley J, Norman R. The use of low dose aspirin in pregnancy induced hypertension. 23rd South African Congress of Obstetrics and Gynaecology; 1986 September 23-26; South Africa, 1986:16.
Hermida RC, Ayala DE, Iglesias M, Mojon A, Silva I, Ucieda R et al. Time-dependant effects of low dose aspirin administration on blood pressure in pregnant women. Hyper Preg 1997;30:589-95.
Bassaw B, Roopnarinesingh S, Roopnarinesingh A, Homer H. Prevention of hypertensive disorders of pregnancy. J Obstet Gynaecol 1998;18:123-6.
Hachicha J, Ammous A, Midassi H, Dammak J, Ghorbel A, Chaabouni MN et al. Place of antiplatelet therapy (APT) in vasculo-renal accidents's (VRA) preventive treatment during pregnancy. 6th International Congress, International Society for the Study of Hypertension in Pregnancy; 1988 May 22-26; Montreal, Quebec, Canada, 1988:144.
Trial of aspirin and methyldopa for moderate hypertension in pregnancy. Personal communication June 3 1993.
McParland P, Pearce JM. Effect of low dose aspirin on maternal and fetal flow velocity waveforms. Am J Obstet Gynecol 1992;166:438.
Williams HD, Howard R, O'Donnell N, Findley I. The effect of low dose aspirin on bleeding times. Anaesthesia 1993;48:331-3.
Hamid R, Robson M, Pearce JM. Low dose aspirin in women with raised maternal serum alpha-fetoprotein and abnormal Doppler waveform patterns from the uteroplacental bed [[retraction Br J Obstet Gynaecol 1995;102:853]] Br J Obstet Gynaecol 1994;101:481-4.
Witten FR. Double-blind, placebo-controlled trial of low-dose aspirin to prevent pre-eclampsia. Personal communication September 6 1991.
O'Grady JP Wilson B. Effects of low-dose aspirin in improving fetal outcome in high risk pregnancies for intrauterine fetal growth retardation and/or preterm delivery. Personal communication March 19 1991.
Sibai BM, Mirro R, Chesney CM, Leffler C. Low-dose aspirin in pregnancy. Obstet Gynecol 1989;74:551-7.
Roberts CS, Beeson JH. Low dose aspirin in the prevention of preeclampsia in nulliparas. Preliminary results of a prospective, placebo-controlled, double blind study. Proceedings of 10th Annual Meeting of Society of Perinatal Obstetricians; 1990; Houston, TX, 1990:89.
Carlson NJ. Trial to evaluate the effectiveness of low dose aspirin versus placebo in the prevention of pregnancy induced hypertension in multiparous patients pregnant with multiple gestations. Personal communication September 6 1991.
Silver RK, MacGregor SN, Sholl JS, Hobart JM, Neerhof MG, Ragin A. Comparative trial of prednisone plus aspirin vs aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients. Am J Obstet Gynecol 1993;169:1411-7.
O'Brien WF, Krammer J, O'Leary TD, Mastrogiannis DS. The effect of acetaminophen on prostacyclin production in pregnant women. Am J Obstet Gynecol 1993;168:1164-9.
Martin C, Varner MW, Branch DW, Rodgers G, Mitchell MD. Dose-related effects of low dose aspirin on hemostasis parameters and prostacyclin/thromboxane ratios in late pregnancy. Prostaglandins 1996;51:321-30.
Wolfrum R, Bordasch C, Holweg J, Schulz G. The therapy of chronic nutritional placenta disorders - preliminary results of a double blind study. Arch Gynaekol 1977;224:114.