Table 27. The effect of maternal vitamin D status in gestation on maternal preeclampsia – Observational studies.
| First Author and year |
Bias score |
Study details |
Study type |
Confounders/ adjustments |
Number of weeks gestation when 25(OH)D was measured | Mean (SD) or Mean (sEM)* or median (IQR) 25(OH)D concentration (nmol/l) in cases | Mean (SD) or median (IQR) 25(OH)D concentration (nmol/l) in controls | Odds ratio/ Relative risk of preeclampsia from univariate analysis | Odds ratio/ relative risk of pre-eclampsia from multivariate analysis | Conclusion | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Seely, 1992 128 |
2 (med) | Boston, USA 12 cases 24 controls |
Case-control | No adjustments, but cases and controls similar for age, gestation, number Caucasian, height, weight, no. primiparous | Mean 35.5 (0.6) weeks for cases and 36 (0.4) wks for controls | 73.9 (7.5)* | 89.3 (11.7)* | Unadjusted OR not given | OR not given | No statistically significant relationship seen | ||||||
|
Bodnar, 2007 124 |
8 (low) | Pittsburgh, USA Cohort size=1198 women 55 cases 220 controls All women nulliparous |
Nested case-control |
Controls randomly selected and un-matched Adjusted for: Maternal race/ethnicity, pre-pregnant BMI, education, season, gestational age at collection |
2 occasions: Before 22 weeks Pre-delivery |
Adjusted geometric mean (<22 weeks): 45.4 (38.6-53.4) Adjusted geometric mean at delivery 54.4 (45.1-65.7) |
Adjusted geometric mean (<22 weeks): 53.1 (47.159.9) Adjusted mean at delivery 64.7 (56.4-74.2) |
Unadjusted OR not given |
At <22 weeks: Adjusted OR for pre-eclampsia Serum 25(OH)D OR (95% CI) <37.5 5 (1.7, 14.1) 50 nmol/l reduction in 25(OH)D increased risk of pre-eclampsia OR 2.4; (95% CI 1.1-5.4) At delivery : 25(OH)D significantly lower in cases (15% reduction; p<0.05) |
At <22 weeks a strong inverse relationship between preeclampsia and 25(OH)D was observed (p=0.02) | ||||||
|
Oken, 2007 131 |
5 (low) | Project Viva, Eastern Massachusetts, USA n=1718 women Cases= 59 |
Cohort | Maternal age, BMI, first trimester systolic BP, ethnicity, education, parity, total energy intake | Not measured FFQ at mean 10.4 weeks |
Not measured Mean intake (IU/day)= 466 (183) |
Not measured Mean intake (IU/day)= 492 (210) |
Unadjusted OR not given | OR (per 100 IU increase in Vitamin D intake per day) of developing preeclampsia = 0.99 (0.87, 1.13) | No significant relationship seen | ||||||
|
Azar, 2011 130 |
5 (low) | Oklahoma, USA All white women with Type 1 diabetes Cohort = 151 women 23 cases 24 controls |
Nested case-control |
Cases and controls matched for age, diabetes duration, HbA1c and parity. Higher BMI and lower HDL cholesterol in the cases Adjusted for parameters that differed between groups (BMI and HDL cholesterol) |
3 visits Mean 12.2 (1.9) wks Mean 21.6 (1.5) wks Mean 31.5 (1.7 weeks) |
Visit 1 | 44.4 (32.9-51.4) |
Visit 1 | 47.2 (37.4-58.2) |
Visit 1 (early pregnancy) |
0.91 (0.88-0.95) |
Visit 1 | 0.99 (0.77-1.30) |
No statistically significant relationship seen at any time point (after adjusting for confounders) | ||
| Visit 2 | 44.2 (35.7-58.2) |
Visit 2 | 43.4 (30.0-61.4) |
Visit 2 (mid-pregnancy) |
1.02 (0.98-1.06) |
Visit 2 | 1.02 (0.78-1.33) |
|||||||||
| Visit 3 | 47.2 (23.5-55.4) |
Visit 3 | 44.9 (33.2-65.9) |
Visit 3 (late pregnancy) |
0.90 (0.73-1.11) |
Visit 3 | 0.92 (0.75-1.14) |
|||||||||
|
Baker, 2010 126 ** |
9 (low) | Boston, USA, cohort size =3992 women 44 cases 201 controls |
Nested case-control |
Controls matched by race/ethnicity Adjusted for: Season of blood sampling, maternal age, multiparity, BMI, gestational age at serum collection |
Between 15 and 20 weeks | 75 (47-107) |
98 (680- 114) |
OR for severe pre-eclampsia | Adjusted OR for severe pre-eclampsia | Lower 25(OH)D3 was associated with increased risk of severe pre-eclampsia | ||||||
| 25(OH)D (nmol/l) |
OR (95% CI) |
p value | 25(OH)D (nmol/l) |
Adjusted OR (95% CI) |
p value | |||||||||||
| >75 | 1 (Ref) | - | >75 | 1 (Ref) | - | |||||||||||
| 50-74.9 | 1.53 v(0.67,3.49) | 0.31 | 50-74.9 | 2.16 (0.86,5.40) |
0.10 | |||||||||||
| <50 | 3.63 (1.52,8.65) |
0.004 | <50 | 5.41 (2.02,14.52) |
0.001 | |||||||||||
|
Haugen, 2009 125 |
2 (med) | Norwegian mother and child cohort, Norway n=23,425 women Cases= 1267 |
Cohort | BMI, height, maternal age, maternal education, season of childbirth | Not measured Estimated from FFQ at 22 weeks | Median (5th, 95th percentile) total vitamin D intake (IU/day): Cases= 308 (60,1200) |
Median (5th, 95th percentile) total vitamin D intake (IU/day): 336 (68, 1256) |
OR for pre-eclampsia | OR for pre-eclampsia | Lower total vitamin D intake associated with an increased risk of pre-eclampsia (p<0.001) | ||||||
| Total Vit D intake (IU/day) | OR | Total Vit D intake (IU/day) | OR | |||||||||||||
| <200 | 1 | <200 | 1 | |||||||||||||
| 200-399 | 0.93 (0.81,1.07) |
200-399 | 0.99 (0.85,1.14) |
|||||||||||||
| 400-599 | 0.81 (0.67,0.97) |
400-599 | 0.87 (0.73,1.05) |
|||||||||||||
| 600-799 | 0.69 (0.55,0.87) |
600-799 | 0.77 (0.61,0.96) |
|||||||||||||
| >800 | 0.78 (0.65,0.92) |
>800 | 0.89 (0.89,1.06) |
|||||||||||||
|
Powe, 2010 129 |
4 (med) | Massachusetts General Hospital Obstetric maternal Study, Massachusetts, USA Cohort size=9930 women Cases=39 Controls=131 |
Nested case control | Controls unmatched Adjusted for: BMI, non-white race and summer blood collection |
first trimester | 68.5 (0.48)* nmol/l | 72.0 (2.0)* nmol/l | OR per 25 nmol/l increase in 25(OH)D = 0.86 (0.60,1.25) If Vit D <37.5 nmol/l OR=2.49 (0.89,6.90) |
OR per 25 nmol/l inrease in 25(OH)D = 1.24 (0.78,1.98) If Vit D <37.5 nmol/l OR=1.35 (0.4,4.5) |
No significant relationship seen (p=0.435) | ||||||
|
Robinson, 2010 127 ** |
5 (low) | South Carolina, USA Cases=50 Controls=100 |
Case-control | Controls matched by race and gestational age at sample collection Adjusted for: BMI, maternal age, African American race, gestational age at sample collection |
Time of diagnosis <34 weeks | 45 (32.5-77.5) |
80 (50-110) |
OR per 25 nmol/l increase in 25(OHD = 0.58 (0.43,0.77) | OR per 25 nmol/l increase in 25(OH)D = 0.37 (0.22,0.62) | Lower 25(OH)D associated with increased risk of severe early preeclampsia p<0.001 | ||||||
|
Shand, 2010 114 |
6 (low) | Vancouver, Canada All women had either clinical or biochemical risk factors for preeclampsia△ Cohort=221 women Cases=28 |
Cohort | Maternal age, ethnicity, parity, BMI, season, multivitamin use, smoking | Between 10 and 20 weeks 6 days (mean 18.7 (1.88) weeks) | 42.6 (32.7-72.4) |
50.4 (35.8-68.0) |
Unadjusted values not given | 25(OH)D (nmol/l) |
OR for pre-eclampsia | No significant relationship seen | |||||
| <37.5 | 0.91 (0.31,2.62) |
|||||||||||||||
| <50 | 1.39 (0.54,3.53) |
|||||||||||||||
| <75 | 0.57 (0.19,1.66) |
|||||||||||||||
|
Hossain, 2011 120 |
4 (med) | Karachi, Pakistan Cohort=75 women Cases= not given 26% of women covered their arms, hands and head; 76% also covered their face |
Cross- sectional |
Maternal age, level of exercise, attire, duration of gestation, newborn weight | At delivery | 29.7 (13.7)+ |
36.2 (18.4)+ |
Not given | 25(OH)D3 tertile | Adjusted OR(95% CI) for preeclampsia (systolic BP>140, and/or diastolic BP>90mmHg | Women in the lowest and middle tertile for 25(OH)D3 more likely to meet criteria for Preeclampsia compared to those in the highest tertile. 25(OH)D3 of 50nmol/l maximum identified as the threshold relating to increased risk for preeclampsia | |||||
| Highest tertile | 1.0 (Ref) | |||||||||||||||
| Middle tertile | 11.05 (1.15,106.04) |
|||||||||||||||
| Lowest tertile | 3.38 (0.40,28.37) |
|||||||||||||||
|
Fernandez-Alonso, 2012 115 |
3 (med) | Almeria, Spain Cohort=466 women Cases=7 |
Cohort | Nil | Between 11-14 weeks | Overall mean not given | Not given | Not given | Not given | No significant association between development preeclampsia as a function of first trimester 25(OH)D status (p=0.51) | ||||||
| 25(OH)D conc | n | |||||||||||||||
| <50 | 2 | |||||||||||||||
| 50-75 | 3 | |||||||||||||||
| >75 | 2 | |||||||||||||||
*
Mean (SEM)
**
Severe preeclampsia
+
25(OH)D3 measured
△
Defined as past obstetric history of early-onset or severe preeclampsia, unexplained elevated α-fetoprotein ≥ 2.5 multiples of the median (MoM), unexplained elevated human chorionic gonadatrophin, or low pregnancy-associated plasma protein A ≤ 0.6 MoM