Background
Stage of PE | Characteristic of PE | ↑ Vitamin D |
---|---|---|
Stage 1 | Inflammation-linked abnormal placental implantation | ↓ Predisposition to pro-inflammatory response [20] |
↑ Regulation of genes associated with placental invasion and normal implantation [20] | ||
Stage 2 | Vascular Endothelial dysfunction | ↑ Vascular structure, elasticity and intima-media thickness |
↓ Blood pressure (regulation of renin-angiotension system) [63] | ||
↓Oxidative stress [24] | ||
Proteinuria mediated by renal vascular endothelial growth factor (VEGF) | ↑ Vascular smooth muscle cell proliferation by increasing VEGF gene transcription [19] |
Biological plausibility of the role of vitamin D in PE
Role of vitamin D as an anti-inflammatory agent and immune modulator
Role of vitamin D and blood pressure regulation
Role of vitamin D and vitamin D receptor (VDR) in calcium homeostasis
Methods
Search strategy
Data extraction
Results
Evidence to support the role of vitamin D in PE
Author, Location, Year | Design | Subjects | Time of vitamin D measurement |
---|---|---|---|
Cross-Sectional Studies | |||
August et al., USA, 1992 [88] | Cross-sectional | 11 – women with PE | 3rd trimester |
9 – chronic HTN | |||
12 – normotensive pregnant controls | |||
Fernandez- Alonzo et al., Spain, 2012 [97] | Cross-sectional | 466 – pregnant women (7 had PE) | 1st trimester |
Pena HR, et al. Brazil 2015 [83] | Cross-sectional | 179 -- pregnant women recruited before delivery | Near delivery |
Case Control Studies | |||
Abedi et al., Iran, 2014 [84] | Case Control | 59 – women with PE | At delivery |
59 – healthy pregnant controls | |||
Achkar et al., Canada, 2015 [81] | Case Control | 169 – women with PE | <20 weeks gestation |
1975 – healthy pregnant controls | |||
Anderson et al., USA, 2015 [111] | Case control | 11 -- gestational HTN (10/11 with PE) | At delivery |
37 – healthy pregnant controls | |||
Baker et al., 2010 [80] | Nested Case Control | 51 – developed PE | 2nd trimester |
204 – healthy pregnant controls | |||
Bodnar et al., USA, 2007 [18] | Nested Case Control | 55 – developed PE | <22 weeks |
219 – healthy pregnant controls | |||
Bodnar et al., USA, 2014 [79] | Case Control | 717 – developed PE | <26 weeks gestation |
560 mild; 157 severe
| |||
2986 – healthy pregnantcontrols | |||
Gidlof S, et al. Sweden, 2015 [112] | Nested Case Control | 39 – developed preeclampsia | 12th week of gestation |
120 – healthy pregnant controls | |||
Halhali, Mexico, 2004 [95] | Case Control | 10 -- developed PE, 40 – healthy pregnant controls | Median 20.7 weeks gestation |
Halhali et al., Mexico, 2007 [113] | Case Control | 26 -- women with PE 26 – healthy pregnant controls | 3rd trimester |
Lechtermann C, et al. Germany, 2–14 [85] | Case Control | 20 – women with PE | At delivery |
43 – healthy pregnant controls | |||
Mohaghegh et al., Iran, 2015 [89] | Case Control | 41 -- women with PE 50 – healthy pregnant controls | Time of labor |
Powe, USA, 2010 [86] | Nested Case Control | 39 -- developed PE 131 – healthy pregnant controls | 1st trimester |
Robinson et al., USA, 2010 [25] | Case Control | 50 -- women with EOSPE | 29 weeks gestation |
100 – healthy pregnant controls | |||
Schneuer et al., Australia, 2014 [114] | Nested Case Control | 5109 pregnant women (223 with PE and 29/223 with EOSPE) | 10–14 weeks gestation |
Singla et al., India, 2015 [87] | Case Control | 74 -- nulliparous women with PE | >30 weeks gestation |
100 -- healthy nulliparous controls | |||
Ullah et al., Bangladesh, 2013 [82] | Case Control | 33 -- women with PE | >20 weeks gestation |
79 – normal pregnancy controls | |||
Wetta et al., UK, 2013 [96] | Case Control | 100 -women with PE | 15–21 weeks gestation |
200 – healthy pregnant controls | |||
Woodham et al., USA, 2011 [15] | Nested Case Control | 41 – women with severe PE | 2nd Trimester |
121 – uncomplicated birth controls | |||
Xu et al., USA, 2014 [53] | Case Control | 100 – women with PE | ≤ 24 weeks gestation |
100 – uncomplicated birth controls | |||
Yu et al., UK, 2012 [115] | Case Control | 60 –late PE | 11–13 weeks gestation |
30 –early PE | |||
1000 – healthy controls | |||
Retrospective Cohort Study | |||
Alvarez-Fernandez et al., Spain, 2014 [90] | Retrospective Cohort | 257 -- women attending obstetric triage with suspicion of PE | 1st Trimester and 20 weeks of gestation |
Scholl et al., USA, 2013 [78] | Retrospective cohort | 1141 -- low income and minority pregnant women | Entry to care (mean 13.7 ± 5.7 weeks) |
Prospective Cohort Studies | |||
Burris et al., USA, 2014 [94] | Prospective Cohort | 1591 -- pregnant women | 16.4–36.9 weeks gestation |
Haugen et al., Norway, 2000 [77] | Prospective Cohort | 23,423 -- pregnant women | Vitamin D intake at weeks 15, 22, and 30 gestation |
Shand et al., Canada, 2010 [37] | Prospective cohort | 221 -- women at risk for PE | 10–20 weeks gestation |
Wei et al., Canda 2012 [60] | Prospective Cohort | 697 -- pregnant women receiving vitamin C and E supplementation for the prevention of PE | 12–18 weeks gestation, 24-26 weeks gestation |
Wei, Canada, 2013 [14] | Prospective Cohort | 697 -- pregnant women receiving vitamin C and E supplementation for the prevention of PE | 24–26 weeks gestation |
Zhou, China, 2014 [116] | Prospective Cohort | 74 – women with PE | 16–20 weeks gestation |
Author, Location, Year | Key Findings | Results |
---|---|---|
August et al., USA, 1992 [88] | ↓ 1,25OH2D in women with PE vs chronic HTN and normal women | 1,25 OH2D levels: PE: 37.8 +/− 15 pg/ml chronic HTN: 75 +/− 15 pg/ml (p < 0.05); normal women: 65 +/− 10 pg/ml (p < 0.05) |
Fernandez- Alonzo et al., Spain, 2012 [97] | ↔ PE and 25(OH)D levels | 25(OH)D: <49.9 nmol/L: 28.6% (2/7 women); 49.9–74.9 nmol/L: 42.9% (3/7 women); ≥ 74.9 nmol/L: 28.6% (2/7 women) (p = 0.91) |
Pena HR, et al. Brazil 2015 [83] | ↑ frequency of 25(OH)D deficiency <20 ng/mL in PE compared to healthy non obese controls | PE: 52.1% (25 women) Non obese controls: 14.9% (7 women) (P = 0.0006) |
Abedi et al., Iran, 2014 [84] | ↑ vitamin D deficiency (<25.0 nmol/L) in PE cases | OR = 24.04 95% CI: 2.14–285.4 |
Achkar et al., Canada, 2015 [81] | ↑ PE in women with 25(OH)D < 30 nmol/L vs women with at least 50 nmol/L | Adjusted OR: 2.23 95% CI: 1.29–3.83 |
Anderson et al., USA, 2015 [111] | ↔ proportion of women with inadequate <30 ng/mL 25(OH)D levels in HTN group vs control group | 73% (HTN/PE group) vs 69% (control group) (p = 0.22) |
Baker et al., 2010 [80] | ↑ Severe PE in women with 25(OH)D < 50 nmol/L compared to levels of at least 75 nmol/L | Adjusted OR: 5.41 95% CI: 2.02–14.52 (P = 0.001) |
Bodnar et al., USA, 2007 [18] | ↑ PE in women with 25(OH)D < 37.5 nmol/L compared to levels of >37.5 nmol/L | Adjusted OR: 5.0 95% CI: 1.7–14.1 |
Bodnar et al., USA, 2014 [79] | ↓ Severe PE in women with 25(OH)D ≥ 50 nmol/L compared to levels <50 nmol/L | Adjusted RR: 0.65 95% CI: 0.43–0.98 |
Gidlof S, et al. Sweden, 2015 [112] | ↔ 25(OH)D levels in PE and healthy controls; ↔ 25(OH)D deficiency < 50 nmol/L in PE and controls | 25(OH)D: PE: 52.2 ± 20.5 nmol/L; Controls: 48.6 ± 20.5 nmol/ L (p = 0.3); 25(OH)D deficiency: PE: 38%, Controls: 51.7% (p = 0.1) |
Halhali, Mexico, 2004 [95] | ↔ 1,25(OH)2D in women before they developed PE | 1,25(OH)2D: median (interquartile range) PE: 31 pg/mL (26–34) NT: 29 pg/mL (24–36) (p = 0.44) |
Halhali et al., Mexico, 2007 [113] | ↓ 1,25(OH)2D levels in women with PE vs controls | 25(OH)D: PE: 486.7 ± 167.2 nmol/L Controls: 731.1 ± 262.1 nmol/L (p < 0.05) |
Lechtermann C, et al. Germany, 2–14 [85] | ↓ 25(OH)D levels in PE in summer compared to controls, 1,25(OH)2D ↓ only in winter | 25(OH)D: PE:18.2 ± 17.1; Control: 49.2 ± 29.2 ng/mL, (P < 0.001); 1,25(OH)2D: 291 ± 217 vs 612.3 ± 455 pmol/mL (P < 0.05) |
Mohaghegh et al., Iran, 2015 [89] | ↓ mean 25(OH)D in PE compared to pregnant controls without PE | 25(OH)D: PE: 37.9 ± 33.9 nmol/L Controls: 58.2 ± 38.2 nmol/L (p = 0.001) |
Powe, USA, 2010 [86] | ↔ women with PE and controls with 25(OH)D < 15.0 nmol/L | Adjusted OR: 1.35 95% CI: 0.40 to 4.50 |
Robinson et al., USA, 2010 [25] | ↑ EOSPE in women with maternal 25(OH)D levels <=19.6 nmol/L compared to levels >19.6 nmol/L | OR: 3.60 95% CI: 1.71–7.58 (p < 0.001) |
Schneuer et al., Australia, 2014 [114] | ↔ PE or EOSPE and low 25(OH)D (< 25 nmol/L) | Adjusted OR- all PE: 0.46 95% CI: 0.19–1.10 Adjusted OR- EOSPE: 1.40 95% CI: 0.20 to 9.89 |
Singla et al., India, 2015 [87] | ↓ mean serum vitamin D in women with PE vs controls | PE: 24.2 ± 12.4 nmol/L Controls: 36.9 ± 16.7 nmol/L; (p = 0.0001) |
Ullah et al., Bangladesh, 2013 [82] | ↑ PE per 25 nmol/L decrease in 25(OH)D level | Adjusted OR: 1.66 95% CI: 1.05–3.02 |
Wetta et al., UK, 2013 [96] | ↔ between PE and 25-OH D < 30 ng/mL and <37.4 nmol/L | <30 ng/mL Adjusted OR: 1.1 95% CI: 0.6–2.0 Adjusted OR: 1.4 (<37.4 nmol/L) 95% CI: 0.7–3.0 |
Woodham et al., USA, 2011 [15] | ↓ Severe PE in women with 10 nmol/L increase in maternal 25(OH)D level | Adjusted OR: 0.62 95% CI: 0.51–0.76 |
Xu et al., USA, 2014 [53] | ↑ PE in women with vitamin D deficiency (<37.5 nmol/L) | OR: 4.4 95% CI: 1.8–10.8 |
Yu et al., UK, 2012 [115] | ↔ serum vitamin D raw values in PE and controls | 25(OH)D levels: Controls: 46.8 nmol/L (27.8–70.0;) Early PE: 32.2 nmol/L (22.7–50.4); Late PE: 39.2 nmol/L (22.1–63.0) (P = 0.231) |
Alvarez-Fernandez et al., Spain, 2014 [90] | ↑ PE in women with 25(OH)D levels <50 nmol/L compared to levels >50 nmol/L after 20 weeks of gestation | OR: 4.6 95% CI:1.4–15 (P = 0.010) |
Scholl et al., USA, 2013 [78] | ↑ PE in women with 25(OH)D < 49.9 nmol/L and hyperparathyroidism | Adjusted OR: 2.86 95% CI: 1.28–6.41 |
Burris et al., USA, 2014 [94] | ↔ PE and 25(OH)D levels compared at each 25 nmol/L increase in 25 (OH)D | Adjusted OR: 1.14 95% CI: 0.77–1.67 |
Haugen et al., Norway, 2000 [77] | ↓ PE in women taking 10–15 mcg/d as compared with no supplements | Adjusted OR: 0.73 95% CI: 0.58–0.92 |
Shand et al., Canada, 2010 [37] | ↔ PE and 25(OH)D levels <37.5 nmol/L | Adjusted OR: 0.91 95% CI: 0.31–2.62 |
Wei et al., Canda 2012 [60] | ↔ PE and 25(OH)D < 50 nmol/L | Adjusted OR: 1.24 95% CI: 0.58–2.67 (p = 0.58) |
Wei, Canada, 2013 [14] | ↑ PE and women with ↓ PIGF levels and maternal 25(OH)D < 50 nmol/L | Adjusted OR: 2.97 95% CI: 1.23–7.20 |
Zhou, China, 2014 [116] | ↔ PE and 25(OH)D levels | 25(OH)D levels Group A (n = 13): 41.4 ± 6.5 nmol/L; Group B (n = 36): 62.1 ± 7.0 nmol/L; group C (n = 25): 89.6 ± 13.0 nmol/L; (p = 0.900) |
Author, Location, Year | Study Design | Subjects | Intervention | Key Findings | Results |
---|---|---|---|---|---|
Olsen and Secher, Denmark, 1990 [91] | Randomized controlled clinical trial | 5644 pregnant women | 2500 IU vitamin D supplement versus no supplement at week 20 of pregnancy | ↓ PE | 31.5% reduction in the odds (p < 0.005) |
Olsen et al., Europe, 2000 [98] | Randomized placebo controlled clinical trial | 386 women who previously experienced PIH | 2.7 g n-3 fatty acids/day given from 33 weeks until delivery vs olive oil placebo | ↔ PIH recurrence risk | OR = 0.98 95% CI: 0.63–1.53 |