1. Vitamins C and E to Prevent Complications of Pregnancy Associated Hypertension
James M. Roberts, M.D., Leslie Myatt, Ph.D.,et al.
New England Journal of Medicine 2010;362
R3 Min Kyung Kim/Prof. Woo Shik Kim

2. Back ground Pregnancy associated Hypertension Clinical findings
Chronic HTN*
Gestational HTN
Preeclamsia
Time of onset HTN
<20 weeks
third trimester†
≥20 weeks
Degree of HTN
Mild or severe
Mild
Proteinuria‡
Absent
Usually present
Thrombocytopenia
Severe disease
Hepatic dysfunction
*Before pregnancy of diagnosed before 20 weeks
† Third trimester is from week 27 to the end of the pregnancy
‡Defined as ≥1+ by dipstick testing on two occasions or ≥ 300mg/24hrs
Gestational age
0 day
20 weeks
27weeks
delivery

3. Back ground Preeclampsia 16% of pregnancy-related deaths
Preeclamsia: 10% of pregnancy
Hypertensive disorders in pregnancy are most significant unsolved problems in obstetrics
2005%
2006%
전 체%
Pregnancy associated hypertension
19.7
12.1
15.7
중증의 전자간증
8.2
4.5
6.3
상세불명의 전자간증
1.6 6
3.9
임신 자간증
4.9
1.5
3.1
산후 자간증
0.8
시기 상세불명의 자간증
3.3
Bleeding
26.2
27.3
26.8
Thromboembolism
21.3
13.6
17.3

4. Reactive oxygen species
Preeecalmpsia: two stage disorder
Abnormal placentation or perfusion
 Inflammatory response
Endothelial dysfunction characteristic maternal syndrome
Cytokine ↑(TNF-α,IL-6)
Oxidative stress:
Reactive oxygen species

5. Back ground Antioxidant supplementation with vitamins C and E
Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial
Lancet 1999; 354: 810–16
Supplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease.
But larger randomized trials involving women at high risk and women at low risk. None of these studies replicated the original positive findings.
To detect a modest effect size in serious outcomes associated with preeclampsia among low risk women with treatment beginning early in the pregnancy

6. Methods Exclusion criteria Inclusion criteria 31,917 women
13,113 run in
10,154 randomization
4,993
Vitamins C and E
4,976
Placebo
Period:
Double blind randomization
Run in period 2wk
Delivery
Proteinuria, Uterine problems(ex.bleeding), fetal problems(ex.anomaly),in vitro ferilization, abuse of illicit drugs or alcohol
Taking Vit C ≥ 150mg, ≥ 75IU vitamin E
antiplatelet drugs, NSAIDs
Inclusion criteria
Screening: Singleton with GA<16wks 0d
Randomization: 9wks 0d-16wks 6d

7. + One or more of the following
Preterm birth (<30wks) by HTN
Fetal/neonatal death
Primary outcome
Severe pregnancy associated hypertension alone
(Severe SBP≥160mmHg ,DBP≥110mmHg)
Severe or mild pregnancy associated hypertension
(mild:SBP , DBP )
+ One or more of the following
Secondary outcome
Pulmonary edema
Thrombocytopenia < 100,000/m3
HELLP syndrome :
-complication of severe preeclamasia
-Hemolysis, Elevated liver enzyme, Low platelet
Preeclamsia
Mild
Severe
proteinuria
300mg/24hrs
5g/24hrs
≥ +2 dip stick
oliguria
Pro/Cr ≥ 0.35

8. Study population Taking a Vitamin at the time of randomization: 77%
Compliance in both group: 88%
Reported side effect (ex. Nausea, vomiting):
 no significant deference

9. Pirmary outcome
There was no significant between group difference in any component of the primary outcome

10. Secondary outcome
No benefit of therapy

11. Results Neonatal outcome
Rates of adverse neonatal outcomes also did not differ significantly between the groups

12. Summary and Conclusion
Supplementation with vitamin C (at a dose of 1000 mg daily) and vitamin E (at a dose of 400 IU daily) did not reduce the rates of either serious adverse outcomes of pregnancy associated hypertension or preeclampsia among low-risk, nulliparous women.
Previous studies have shown a similar lack of efficacy
among high-risk women
among women who were likely to have had a deficiency of vitamins C and E
The findings of these several studies provide no support for the use of vitamin C and E supplementation in pregnancy to reduce the risk of preeclampsia or its complications