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. 2022 Nov 9;77(7):710–730. doi: 10.1038/s41430-022-01232-0

Table 4.

Screening at study entry and micronutrient supplementation interventions in included studies.

Reference Screening for pre-eclampsia Intervention Gestational age during intervention
Hofmeyr et al. Women with previous pre-eclampsia and were intending to become pregnant again

I = 500 mg of calcium carbonate daily from prepregnancy until 20 weeks’ gestation

C = Placebo

From prepregnancy to 20 weeks’ gestation
Baba Dizavandy et al. Nulliparous women with singleton pregnancies, 24 weeks of gestation, blood pressure <140/90 mmHg, a positive roll-over test and hypocalcuria at 28–32 weeks of pregnancy

I = 2000 mg of calcium gluconate daily

C = Placebo

From 28–32 weeks gestation to delivery
Herrera et al. First pregnancy, gestation between 28–32 weeks, biopsychosocial risk score of 3 or more, positive roll-over test and high mean arterial pressure

I = 50 mg of linoleic acid and 600 mg of calcium daily

C = Placebo

From 28–32 weeks’ gestation to delivery
Niromanesh et al. High-risk for pre-eclampsia (identified as having positive results on rollover test and at least one risk factor for pre-eclampsia), gestational age between 28–32 weeks, blood pressure <140/90 mmHg

I = 2000 mg of calcium daily

C = Placebo

Until delivery
Sanchez-Ramos et al. Normotensive nulliparas at 20–24 weeks’ gestation at increased risk of developing pregnancy-induced hypertension (through positive angiotensin sensitivity test)

I = 2000 mg of calcium daily

C = Placebo

Not reported
Behjat et al. Pre-eclampsia in previous pregnancy, serum 25-hydroxy vitamin D levels >25 ng/ml

I = 50000 IU of vitamin D3 every 2 weeks

C = Placebo

Until 36 weeks’ gestation
Karamali et al. Pregnant women primigravida, age of 18–40 and risk of pre-eclampsia (identified through uterine artery Doppler)

I = 50000 IU of vitamin D3 every 14 days

C = Placebo

From 20 weeks’ to 32 weeks’ gestation
Samimi et al. Primigravida women, aged 18–40 years old, at risk for pre-eclampsia (indicated by laboratory tests including free ß-human chorionic gonadotrophin, inhibin α dimeric, unconjugated oestriol and maternal serum α-foetoprotein and haemodynamic assessment of uterine artery Doppler waveform at 16–20 weeks of gestation)

I = 50000IU of vitamin D3 every 2 weeks and 1000 mg calcium daily

C = Placebo

From 20 weeks’ to 32 weeks’ gestation
Chappell et al. Women with abnormal two-stage uterine-artery doppler analysis weeks and previous history of pre-eclampsia

I = 1000 mg of vitamin C and 400 IU of vitamin E daily

C = Placebo

From 16–22 weeks’ gestation (depending on prior history of pre-eclampsia) to delivery
Poston et al. Gestational age 14–21 weeks 6 days and one or more risk factors for pre-eclampsia including pre-eclampsia in the pregnancy preceding the index pregnancy, requiring delivery before 37 completed weeks’ gestation, diagnosis of HELLP syndrome in any previous pregnancy at any stage of gestation, essential hypertension requiring medication currently or previously, maternal diastolic blood pressure of ≥90 mmHg before 20 weeks’ gestation in the current pregnancy, type 1 or type 2 diabetes requiring insulin or oral hypoglycaemic therapy before the pregnancy, antiphospholipid syndrome, chronic renal disease, multiple pregnancy, abnormal uterine artery doppler waveform, primiparity with BMI at first antenatal appointment of ≥30

I = 1000 mg of vitamin C and 400IU vitamin E daily

C = Placebo

From 14–21 weeks’ gestation to delivery
Spinatto et al. Pregnant women between 12 and 19 6/7 weeks gestation, non-proteinuric chronic hypertension or with a prior history of preeclampsia in their most recent pregnancy that progressed beyond 20 weeks gestation

I = 1000 mg of vitamin C and 400IU of vitamin E daily

C = Placebo

From 12–19 weeks’ gestation to delivery
Kalpdev et al. Essential hypertension, singleton pregnancy, gestational age 16 to 22 weeks

I = 1000 mg of vitamin C and 400IU of vitamin E daily

C = No supplementation

From 16–22 weeks’ gestation to delivery
Beazley et al. Pregnancy at 14–20 weeks and 6 days with a history of previous pre-eclampsia, chronic hypertension, insulin-requiring diabetes or multiple gestation

I = 1000 mg of vitamin C and 400IU of vitamin E daily

C = Placebo

From 14–20 weeks’ gestation
Vadillo-Ortega et al. Increased risk of pre-eclampsia (history of pre-eclampsia or pre-eclampsia in a first degree relative)

I = 6.6 g of L-arginine + 500 mg of vitamin C + 400IU of vitamin E daily

I2 = 500 mg of vitamin C + 400IU of vitamin E daily

C = Placebo

From 14–32 weeks’ gestation to delivery
Villar et al. Pregnant women 14–22 weeks of gestation and with high risk for pre-eclampsia (chronic hypertension, renal disease, pre-eclampsia-eclampsia in the pregnancy preceding the index pregnancy requiring delivery before 37 weeks’ gestation, HELLP syndrome in any previous pregnancy, pregestational diabetes, primiparous with a BMI ≥ 30, history of preterm delivery, abnormal uterine artery Doppler waveforms and women with antiphospholipid syndrome)

I = 1000 mg of vitamin C and 400IU of vitamin E daily

C = Placebo

14–22 weeks’ gestation to delivery
Zheng et al. Previous pre-eclampsia, planning pregnancy, aged over 18 years, daily folic acid intake before randomization <1.1 mg

C = Low dose folic acid (0.4 mg) daily

I = High dose folic acid (4 mg) daily

Preconception to delivery
Wen et al. Pregnant women between 8–16 completed weeks of gestation and at least one risk factor for pre-eclampsia including pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy or BMI ≥ 35

I = 4 mg of folic acid daily

C = Placebo

From 8–16 weeks’ gestation to delivery
De Araujo et al. Women aged 18 to 45 years, 12 to 20 weeks of gestation, singleton pregnancy and ≥1 risk factor for preterm birth or adverse perinatal outcomes in a prior pregnancy (i.e. preterm delivery <37 weeks, still birth at 201/7 weeks, placental abruption, pre-eclampsia or eclampsia, a live-born infant with SGA birthweight <3rd percentile or liveborn infant with birthweight <2500 g) or in current pregnancy (i.e. nulliparity, chronic hypertension, type 1 or 2 diabetes mellitus, maternal age >35 years, pre-pregnancy BMI > 30 or smoking)

I = 300 mg of magnesium citrate daily

C = Placebo

From 12–20 weeks’ gestation to delivery
Azami et al. Women with at least one risk factor for pre-eclampsia (including chronic vascular disease, hydatidiform mole, multiparity, diabetes mellitus, thyroid disease, chronic hypertension, nulliparity, history of pre-eclampsia, maternal age >35 years, kidney disease, collagen vascular disease, antiphospholipid antibody syndrome, family history of pre-eclampsia, history of thrombophilia and BMI > 25)

I1 = Ferrous sulfate tablet + one multimineral vitamin D tablet containing 800 mg of calcium, 8 mg of zinc and 400IU of vitamin D3 daily

I2 = Ferrous sulfate tablet + 250 mg of vitamin C and 55 mg of vitamin E daily

C = Ferrous sulfate tablet daily

From 20 weeks’ gestation to delivery
Parrish et al.

For low risk group: nulliparous or multiparous women, singleton gestation and no evidence of systemic vascular disease

For high risk group: multiparous patients with singleton gestation and a prior history of preeclampsia (prior eclampsia, prior mild or severe preeclampsia, prior HELLP) or nulliparous/multiparous patients with singleton gestation with a documented history of chronic hypertension, diabetes mellitus, connective tissue disease or inherited/acquired thrombophilia

I = Phytonutrients (7.5 mg beta-carotene, 234 mg vitamin C, 30 mg vitamin E, 420 mg folate and 60 mg calcium - mix through a concentrate of blended fruit and vegetable juice powder) taken twice daily until delivery

C = Placebo

Any time up to 12 weeks’ gestation until delivery