Vitamin D and Nifedipine in Preeclampsia

Achaia Taltoan, Mercer University College of Pharmacy

Preeclampsia is a syndrome characterized by a persistent blood pressure ≥ 140/90 mmHg and urine protein ≥ 300 mg/24 hours after 20 weeks of gestation. The American College of Obstetrics and Gynecology guidelines on pregnancy induced hypertension recommend immediate release nifedipine as one of the first line agents for treatment of blood pressure ≥ 160/110 mmHg. [1]

Although the pathogenesis of preeclampsia is unclear, some evidence suggests that vitamin D plays a role in the emergence of preeclampsia. [2] It is thought that vitamin D deficiency is associated with increased TNF-α and decreased IL-10 that are linked to hypertension during pregnancy and preterm birth. [2] The role of vitamin D as an antihypertensive agent for preeclampsia has not been assessed in human patients until this trial was conducted. [3]

Vitamin D enhances efficacy of oral nifedipine in treating preeclampsia with severe features: a double blinded, placebo-controlled and randomized clinical trial
Design Double blind, placebo-controlled, randomized control trial; N= 683
Objective To evaluate the efficacy and adverse effects of vitamin D and nifedipine in hypertension treatment in preeclampsia patients
Study Groups Nifedipine 10 mg/capsule + Vitamin D 200 IU/capsule (n= 298), nifedipine 10 mg/capsule +placebo (glucose 20 mg/capsule) (n= 304)
Methods Inclusion Criteria

·       Primigravid female

·       20-30 weeks gestation age

·       Proteinuria ≥ 0.3g protein/24 hours

·       Hypertensive disorder (≥ 150 mmHg systolic and or ≥ 110 mmHg diastolic blood pressure)

Exclusion Criteria

·       History of heart failure during pregnancy

·       History of smoking and or diabetes

·       Use of antihypertensive therapy

·       Use of vitamin D supplementation

 Patients received assigned medication every 15 minutes orally for up to four doses or until blood pressure was ≤ 150/100 mmHg. Therapy was discontinued when either of these conditions were met. Ten milliliters of blood samples were collected from patients after therapy was discontinued, and TNF-α and IL-10 levels were assessed. Adverse events were reported by patients through a survey administered at the end of the trial. Statistical difference was determined using the t-test and Pearson’s-chi square test.


Duration January 2011- December 2016
Primary Outcome Measure Time needed to lower blood pressure of the patients to 150/100 mmHg and time before another hypertensive emergency (blood pressure > 150/100 mmHg)
Baseline Characteristics
Characteristics Nifedipine+ Placebo

(n= 304)

Nifedipine +Vitamin D

(n= 298)

Maternal age 33.2±6.7 32.7± 5.2
Gestation age at enrollment 24.3± 4.1 25.6± 3.4
Pre-treatment systolic blood pressure 169.0± 11.2 171.2 ±13.4
Pre-treatment diastolic blood pressure 108.9 ±12.7 110.2± 13.1
Post-treatment systolic blood pressure 159.6 ±10.8 143.4± 7.6
Post-treatment diastolic blood pressure 101.9± 9.5 97.1± 9.2
Primary Endpoints Nifedipine+ Placebo

(n= 304)

Nifedipine +Vitamin D

(n= 298)

Time to control blood pressure (min) 61.1 ±15.9 41.8 ±18.3 0.013
Time before a new hypertensive crisis (hour) 4.8± 2.6 8.1± 2.2 0.017


Table 1. Efficacy of the two treatments in controlling blood pressure among women with preeclampsia




Number of Doses


Nifedipine +Placebo

(n= 304)

Nifedipine Vitamin D

(n= 298)

1 dose 17% 27%
2 doses 35% 38%
3 doses 35% 29%
4 doses 13% 6%

Table 2. Number of doses needed to control blood pressure in two groups of patients (estimated percentages; based on figure 2)



Adverse Events Common Adverse Events: (Nifedipine +Placebo vs. Nifedipine+ Vitamin D, n)

Nausea: 13 vs. 11

Vomiting: 7 vs. 8

Maternal tachycardia: 7 vs. 5

Mild headache: 5 vs.5

Dizziness: 4 vs. 4

Chest pain: 2 vs. 3

Hypotension: 2 vs. 1

Shortness of breath: 2 vs.1


Serious Adverse Events: not disclosed
Percentage that Discontinued due to Adverse Events: not disclosed
Study Author Conclusions Vitamin D is a beneficial adjuvant to oral nifedipine in treating hypertensive emergency in preeclampsia.

The use of up to four doses of nifedipine does not appear to be a standard practice. The ACOG sample order set suggests using up to three doses (10 mg once plus two doses of 20 mg) then switching to IV labetalol. [4] Additionally, in a clinical setting, use of ineffective treatment after three trials for such conditions may be unlikely as they require urgent resolution of symptoms. Therefore, this protocol may not reflect the general clinical practice. The patients’ OTC vitamin D use was not considered which may have influenced the overall vitamin D levels and the outcome. Obtaining patients’ history of vitamin D deficiency and baseline vitamin D levels may have been helpful additional information to assess the association between vitamin D and hypertension. While the findings of this trial represent a potential additional therapy in pregnancy hypertensive emergency, the data appears to be insufficient to recommend its routine use.


[1] American College of Obstetricians and Gynecologists; task force on hypertension in pregnancy. hypertension in pregnancy. report of the American College of Obstetricians and Gynecologists’ task force on hypertension in pregnancy. Obstet Gynecol. 2013;122(5):1122-31.

[2] Baca KM, Simhan HN, Platt RW, et al. Low maternal 25-hydroxyvitamin D concentration increases the risk of severe and mild preeclampsia. Ann Epidemiol. 2016;26(12):853-857.e1.

[3] Shi DD, Wang Y, Guo JJ, et al. Vitamin D enhances efficacy of oral nifedipine in treating preeclampsia with severe features: a double blinded,placebo-controlled and randomized clinical trial. Front Pharmacol. 2017; 8:865.

[4] Committee on Obstetric Practice. Committee opinion no. 692: emergent therapy for acute-onset, severe hypertension during pregnancy and the postpartum period. Obstet Gynecol. 2017;129(4): e90-e95.
















































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