Table 3 Association between vitamin D and pre-eclampsia (PE) in observational studies

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)