Table 5.

Diagnostic criteria and outcomes of included studies.

Reference	Diagnostic criteria for pre-eclampsia	Pre-eclampsia	Classifications of pre-eclampsia	Other outcomes
Hofmeyr et al.	Gestational hypertension (DBP > 90 mmHg on two occasions 4 h apart, or >110 mmHg once, or SBP > 140 mmHg on two occasions 4 h apart, or >160 mmHg once after 20 weeks’ gestation) and gestational proteinuria (2 r more on urine dipstick, or >300 mg/24 h or 500 mg/L or urinary protein:creatinine ratio >0.034 g/mmol after 20 weeks’ gestation) as diagnosed by the attending clinicians. Severe pre-eclampsia (proteinuria + severe DBP [>110 mmHg] or systolic [>160 mmHg] hypertension)	I = 69/296 (23%) vs C = 82/283 (29%), [RR = 0·80 (95% CI 0·61–1·06)], p = 0.121	I = 52/296 (18%) vs C = 60/283 (21%), [RR = 0.83 (95% CI 0.59–1.16)], p = 0.268	Not significant
Baba Dizavandy et al.	Having both gestational hypertension (SBP increase ≥30 mmHg and DBP increase ≥15 mmHg on two occasions at least 6 h apart, or SBP ≥ 140 mmHg and DBP ≥ 90 mmHg after 24 weeks’ gestation in absence of proteinuria) and proteinuria (>0.3 g/L urine on at least two separate random urine specimens more than 6 h apart after 24 weeks’ gestation)	I = 0% vs C = 3.3%	Not reported	Gestational hypertension: I = 11.4% vs C – 31.2%, p < 0.01 Pregnancy-induced hypertension: I = 11.4% vs C = 35.6%, p < 0.01 Serum calcium levels vs. SBP in C group: r = −0.28, p = 0.02
Herrera et al.	Development of hypertension from 20 weeks’ gestation (≥140/90 mmHg where there is an increase of ≥20 mmHg in DBP compared to previous levels during pregnancy on at least two occasions 6 or more hours apart) and significant 24-hour proteinuria (>0.3 g/L) in the absence of a urinary tract infection	I = 4 (9.3%) vs C = 16 (37.2%), [RR = 0.25], p = 0.002	Not reported	DBP: I = 74.6 ± 11.2 mmHg vs C = 81.9 ± 11.9 mmHg, p = 0.001 Gestational age at birth: I = 39.3 ± 1.4 weeks vs C = 38.2 ± 2.3 weeks, p = 0.03 Caesarean: I = 10 (23.3%) vs C = 19 (44.2%), p = 0.04 Birth weight: I = 3180 ± 340 g vs C = 3056 ± 475 g, p = 0.03 PGE2 levels after 30 days: I = + 106% vs C = −33%, p = 0.02
Niromanesh et al.	SBP of ≥140 mmHg (an increase of 30 mmHg) and DBP ≥ 90 mmHg (an increase of 15 mmHg) on two occasions at an interval of 4–6 h with proteinuria (1 + proteinuria on random sampling of urine, measured as sulfosalicylic acid)	I = 1/15 vs C = 7/15, p = 0.014	Not reported	Time of onset of pre-eclampsia: I = 37 weeks vs C = 34 weeks, p < 0.05 Time of onset of hypertension: I = 37 ± 2 weeks vs C = 34 ± 1.9 weeks, p < 0.040 Duration of pregnancy: I = 39.5 ± 0.8 weeks vs C = 37.7 ± 2.5 weeks, p < 0.05 Infant birth weight: I = 3316 ± 308 g vs C = 2764 ± 761 g, p < 0.05
Sanchez-Ramos et al.	BP ≥ 140/90 mmHg measured twice at 4–6 h apart and significant proteinuria (≥1+ on dipstick or at least 300 mg/2 h)	I = 13.8% vs C = 44.1%, p = 0.01, [RR = 0.37, (95% CI 0.15–0.92)]	Mild pre-eclampsia: I = 3/29 vs C = 9/34 Severe pre-eclampsia: I = 1/29 vs C = 6/34	Pregnancy-induced hypertension: I = 31.0% vs C = 64.7%, p = 0.01 [RR = 0.46, 95% CI 0.25–0.86]
Behjat et al.	BP ≥ 140/90 mmHg in sitting position with proteinuria of ≥1+ on urine dipstick	I = 11 (15.7%) vs C = 22 (30.6%), p = 0.036 Risk in the control group was 1.94 times higher (95% CI 1.02–3.71)	Not reported	Not reported
Karamali et al.	Not reported	I = 3.3% vs C = 10.0%, p = 0.30	Not reported	Serum vitamin D levels: I = 17.92 ± 2.88 ng/ml vs C = 0.27 ± 3.19 ng/ml, p = 0.001 Increase in insulin levels: I = 1.08 ± 6.90 µIU/ml vs C = 9.57 ± 10.32 µIU/ml, p < 0.001)
Samimi et al.	Not reported	I = 3.3% C = 10.0%, p = 0.30	Not reported	Change in DBP: I = −2.0 mmHg, SD 6.6 mmHg vs C = + 3.7 mmHg, SD 6.3 mmHg, p = 0.001 Change in SBP: I = −3.8 mmHg, SD 5.8 mmHg vs C = + 1.7 mmHg, SD = 8.7 mmHg, p = 0.006 Mean serum 25(OH) D concentration: I = 8.2 ng/mL, SD = 7.7 ng/mL vs C = + 0.1 ng/mL, SD = 3.2 ng/mL, p < 0.001 Change in FPG: I = −5.7 mg/dL, SD = 5.5 mg/dL vs C = −0.6 mg/dL, SD = 12.6 mg/dL, p = 0.04 Change in insulin: I = −0.28 µIU/ml, SD = 6.0 µIU/ml vs C = + 7.7 µIU/ml, SD = 9.0 µIU/ml, p < 0.001 Change in HOMA-IR: I = −0.8, SD = 1.3 vs C = + 1.6, SD = 2.2, p < 0.001 Change in HOMA-B: I = −8.2, SD = 25.8 vs C = + 32.6, SD = 41.3, p < 0.001 Change in QUICKI score: I = + 0.02, SD = 0.02 vs C = −0.02, SD – 0.02, p < 0.001 Change in Serum HDL cholesterol: I = + 4.6 mg/dL, SD = 8.3 mg/dL vs C = −2.9 mg/dL, SD = 7.7 mg/dL, p = 0.001 Change in plasma GSH concentration: I = + 23.4 µm, SD = 124.0 µm vs. C = −94.8 µm, SD = 130.2 µm, p = 0.001
Chappell et al.	Two recordings of DBP ≥ 90 mmHg at least 4 h apart (for severe pre-eclampsia, two recordings of DBP ≥ 110 mmHg at least 4 h apart or one reading of 120 mmHg) and proteinuria (excretion of 300 mg or more in 24 h or two readings of ≥2+ on midstream urine dipstick or catheter urine if 24-hour collection is not available) Superimposed pre-eclampsia was defined as the new development of proteinuria in women with chronic hypertension	ITT I = 11/141 (8%) vs C = 24/142 (17%) [Adj OR = 0.39 (95% CI 0.17–0.90)], p = 0.02	Mild pre-eclampsia: ITT I = 5/141 vs C = 13/142 Severe pre-eclampsia: ITT I = 3/141 vs C = 5/142 Superimposed pre-eclampsia: ITT I = 3/141 vs C = 6/142	PAI-1:PAI-2 ratio: 21% reduction in I (85% CI 4–35), p 0.015
Poston et al.	Gestational hypertension (two or more readings of DBP ≥ 90 mmHg taken at least 4 h and up to 168 h apart, occurring after 20 weeks’ gestation or up to 48 h in the early postnatal period, excluding labour) or severe gestational hypertension (same as above however with a DBP ≥ 110 mmHg on two or more occasions or a single reading of ≥120 mmHg), and proteinuria (excretion of 300 mg/24 h protein or two readings of ≥2+ on urine dipstick analysis) or severe proteinuria (excretion of ≥5000 mg/24 h)	I = 181 (15%) vs C = 187 (16%) [RR = 0·97, 95% CI 0·80–1·17], p = 0.754	Severe pre-eclampsia: I = 62 (5%) vs C = 53 (4%) [RR = 1.17, 95% CI 0.82–1.68]	Gestational hypertension: I = 84 (7%) vs. C = 55 (5%), [RR = 1.53, 95% CI 1.10–2.13] Low birth weight: I = 387 (28%) vs C = 335 (24%), p = 0.023 [RR = 1.15, 95% CI 1.02–1.30] Low birth weight in women with diabetes: I = 20% {n = 19) vs C = 10% (n = 6), risk ratio = 3.26 95% CI 1.36–7.84
Spinatto et al.	SBP ≥ 140 mmHg and DBP ≥ 90 mmHg or proteinuria (either 300 mg/24 hours or ≥2+ by dipstick on two or more occasions 4 h apart) Severe pre-eclampsia defined as severe hypertension (if ≥ 2 SBP values obtained 4 or more hours apart were 160 mmHg or if ≥2 DBP values were 110 mmHg) and proteinuria; urinary protein excretion 5 g/day with any degree of hypertension; hypertension complicated by pulmonary oedema or a low platelet count (<100,000/mL); or haemolysis, an elevated serum aspartate aminotransferase concentration (>70 units/L), and a low platelet count (HELLP syndrome). Superimposed pre-eclampsia was defined as hypertension + proteinuria (either 300 mg/24 h or ≥2+ by dipstick) in chronically hypertensive patients	ITT I = 49/355 (13.8%) vs C = 55/352 (15.6%), [Adj RR = 0.87, (95.42% CI 0.61–1.25)], p = 0.43	Severe pre-eclampsia in those without chronic hypertension: I = 11/170 (6.5%) vs C = 4/168 (2.4%), p = 0.11, [OR = 2.78, 95% CI 0.79–12.62]	Premature rupture of membranes: I = 10.6% vs C = 5.5%, p = 0.015 [RR = 1.89, 95% CI 1.11–3.23]
Kalpdev et al.	Superimposed pre-eclampsia was defined as the new onset proteinuria of ≥300 mg/24 h in hypertensive women with no proteinuria before 20 weeks’ gestation or a sudden increase in proteinuria or BP or platelet count of <100,000 mm3 in women with hypertension and proteinuria before 20 weeks’ gestation	N/A	Superimposed pre-eclampsia: I = 8% vs C = 12%, p = 1.000	FRAP levels: I = 1168.95 ± 191.32 µM vs C = 835.93 ± 162.35 µM, p = 0.022
Beazley et al.	Not reported	I = 17.3% vs C = 18.8% [RR = 0.92, 95% CI 0.4–2.13]	Severe pre-eclampsia: I = 3/52 vs 3/48 Total cases of mild pre-eclampsia: 5 Total cases of superimposed pre-eclampsia: 7	Not significant
Vadillo-Ortega et al.	Hypertension (SBP ≥ 140 mmHg, DBP ≥ 90 mmHg, or both) and proteinuria (>300 mg/24 h) after 20 weeks’ gestation in women known to be previously normotensive Severe pre-eclampsia defined as proteinuria >2.0 g/24 h, BP ≥ 160/110 mmHg or both	Incidence of pre-eclampsia and eclampsia together: L-arginine + antioxidant vitamins (I) vs placebo (C) = lower incidence in I [χ2 = 19.41, p < 0.001, ARR 0.17, 0.12–0.21] No differences between antioxidants (I2) group vs placebo (C), p = 0.052	Not reported	Preterm delivery: I = ARR = 0.53 [95% CI 0.33–0.84, χ2: p = 0.003], I2 = ARR = 0.44 [95% CI 0.28–0.70, χ2: p < 0.001] Side-effects: Significantly more side-effects in I than C: nausea (p = 0.019), symptoms of dyspepsia (p = 0.04), dizziness (p = 0.039), palpitations (p = 0.019) and headache (p = 0.09) 1-minute Apgar score: I vs C ARR = 0.44, 95% CI% 0.24–0.64, p = 0.000 I2 vs C ARR = 0.25, 95% CI = 0.04–0.47, p = 0.015 I vs I2 ARR = 0.18, 95% CI 0.01 = 0.36, p = 0.04 5-minute Apgar score: I vs C ARR = 0.21, 95% CI 0.10–0.33, p = 0.000
Villar et al.	De novo hypertension (≥2 readings of DBP ≥ 90 mmHg, taken 4 h apart or more, but <160 h apart, and occurring after 20 weeks’ gestation) and new-onset proteinuria (excretion of ≥300 mg/24 h or two readings of >1+ on dipstick if 24-h collection is not available) Severe pre-eclampsia defined as SBP ≥ 160 mmHg and/or DBP ≥ 110 mmHg on two occasions, at least 4 h but not more than 168 h apart, or if the first measurement was immediately followed by treatment with an antihypertensive, either of these scenarios being associated with proteinuria.	I = 24.1% vs C = 23.3% [RR = 1.0, 95% CI 0.9–1.3]	Severe pre-eclampsia: I = 3.2% vs C = 4.3% [RR = 0.8, 95% CI 0.4–1.3]	Not significant
Zheng et al.	BP ≥ 140/90 mmHg and proteinuria Severe pre-eclampsia diagnostic criteria not reported	Overall pre-eclampsia: Low dose group = 37/378 (9.8%) vs High dose group = 42/410 (10.2%) [RR = 0.96, 95% CI 0.76–1.19)], p = 0.684	Severe pre-eclampsia: Low dose group = 64/378 (16.9%) vs High dose group = 40/410 (9.8%) [RR = 1.69. 95% CI 0.55–4.80], p = 0.011	Severe gestational hypertension: Low dose group = Low dose group = 126/378 (33.3%) vs high dose group = 89/410 (21.7%), p = 0.021 [RR = 1.54, 95% CI = 0.67–3.70] Early onset of pre-eclampsia (<32 weeks): Low dose group = 73/378 (19.3%) vs high dose group = 52/4410 (12.7%), p = 0.039 [RR = 1.52, 95% CI 0.53–4.20] Apgar score <7 at 5 min: Low dose group = 5/378 (1.3%) vs high dose group = 3/410 (0.7%), p = 0.013 [RR = 1.85, 95% CI 0.44–4.32]
Wen et al.	DBP ≥ 90 mmHg on two occasions 4 or more hours apart and proteinuria (≥2+ on dipstick, or urinary protein ≥300 mg/24 h, or random protein:creatinine ratio ≥30 mg protein/mmol) in women at ≥20 weeks’ gestation, or diagnosis of HELLP syndrome or superimposed pre-eclampsia (history of pre-existing hypertension diagnosed before pregnancy or before 20 weeks’ gestation with new proteinuria) Severe pre-eclampsia diagnostic criteria not reported	I = 169/1144 (14.8%) vs C = 156/1157 (13.5%) [RR = 1.10, 95% CI 0.90–1.34] p = 0.37	Severe pre-eclampsia: I = 21/1144 (1.84%) vs C = 16/1156 (1.38%) [RR = 1.52, 95% CI 0.81–2.84], p = 0.19	Not significant
De Araujo et al.	Elevated SBP > 140 mmHg or DBP > 90 mmHg, with ≥2+ proteinuria on urine dipstick, and/or HELLP syndrome	I = 24 (5.9%) vs C = 20 (4.7%), [unadjusted RR = 1.24 (0.70 to 2.22)], [Adj OR = 1.25 (0.68 to 2.31)]	Not reported	Placental abruption: I = 9 (2.2%) vs C = 21 (5.0%), unadjusted RR = 0.44 (0.21–0.96), Adj OR = 0.43 (0.20–0.95)
Azami et al.	BP ≥ 140/90 after 20 weeks’ gestation and proteinuria ≥300 mg/24 hours or 1+ on urine dipstick	Group A (I) = 13.3% vs Group C (C) = 36.7%, p = 0.03 Group B (I) = 33.3% vs Group C (C) = 36.7%, p = 0.50 Group A vs Group B, p = 0.063	Not reported	Neonatal complications (unspecified): Lower in Group A (p = 0.01)
Parrish et al.	Not reported	High and low risk group: I = 15.9% vs C = 16.3%, p = 0.93 Low risk group: I = 10.7% vs C = 8.8%, p = 0.73, [RR = 1.22, 95% CI 0.40–3.77] High risk group: I = 19.7% vs C = 21.9%, p = 0.75, [RR = 0.91, 95% CI 0.49–1.68]	Mild pre-eclampsia: Low risk group I = 8.9% vs C = 8.8%, p = 0.98 [RR = 1.02, 95% CI 0.31–3.32]; high risk group I = 2.6% vs C = 1.3%, p = 0.99 [RR = 1.03, 95% CI 0.07–16.1] Severe pre-eclampsia: Low risk group I = 0% vs C = 0%; high risk group I = 5.3% vs C = 3.9%, p = 0.67 [RR = 1.37, 95% CI 0.32–5.91] Superimposed pre-eclampsia: Low risk group I = 0% vs C = 0%; high risk group I = 11.8% vs C = 16.7%, p = 0.40 [RR = 0.71, 95% CI 0.32–1.56]	Not significant

RR relative risk, OR odds ratio, ARR absolute risk reduction, I intervention, C control, ITT intention to treat, Adj adjusted, SD standard deviation, BP blood pressure, DBP diastolic blood pressure, SBP systolic blood pressure’