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Pre-eclampsia and Pregnancy-induced Hypertension

Uses

Principal Proposed Natural Treatments

Pregnant women occasionally experience an increase in blood pressure known as gestational hypertension or pregnancy-induced hypertension (PIH). In a more severe condition called pre-eclampsia, a rise in blood pressure is accompanied by protein in the urine and sometimes by sudden weight gain, swelling in the face or hands, and other symptoms. When left untreated, pre-eclampsia can lead to seizures (called eclampsia) or liver, kidney, or bleeding problems in the mother and distress or delayed growth in the fetus. Unless pre-eclampsia is mild, doctors usually seek to deliver the baby early.

Principal Proposed Natural Treatments

Although there are no fully established natural treatments for the prevention of pre-eclampsia or PIH, calcium has shown significant promise.

Calcium

A meta-analysis (statistical review) of 11 studies of calcium supplementation in pregnancy, involving a total of more than 6,000 women, found that calcium slightly reduced the risk of pre-eclampsia and hypertension, particularly in two groups of women: those at high risk for hypertension and/or those with low calcium intakes. 1
However, by far the largest single study in the meta-analysis found no benefits. 2 In this double-blind study, researchers gave either 2 g of calcium or placebo daily to 4,589 women from weeks 13 to 21 of their pregnancy onward. In the end, researchers found no significant decreases in rates of hypertension or pre-eclampsia—not even when they looked specifically at women whose daily calcium consumption mirrored that of women in developing countries.
The meta-analysis included this negative study in its calculations, but still found that calcium seemed to be helpful.
In a subsequent double-blind, placebo-controlled study published in 2006 and conducted by the World Health Organization, calcium supplements (1.5 g per day) were tried in 8,325 pregnant women whose calcium intake was inadequate. 28 Calcium failed to reduce the incidence of pre-eclampsia. However, it did appear to reduce the severity of pre-eclampsia episodes.
The bottom line: Calcium might be of some benefit for those pregnant women who are at high risk for hypertension or deficient in calcium. However, for well-nourished, low-risk women, effects are likely to be minimal or nil.
All of the above refers to preventing pre-eclampsia. One double-blind, placebo-controlled study suggests that calcium supplements are not effective for treating pre-eclampsia that has already developed. 3
Note: Calcium appears to offer the additional benefit of reducing blood levels of lead during pregnancy. 4
Interestingly, weak evidence hints that use of calcium by pregnant mothers might reduce risk of hypertension in their children. 33
For more information, including dosage and safety issues, see the full Calcium article.

Other Proposed Natural Treatments

Antioxidants are substances that fight free radicals, dangerous naturally occurring molecules that may play a role in pre-eclampsia. For various theoretical reasons, it has been proposed that use of antioxidants by pregnant women may help stop pre-eclampsia from developing. One double-blind, placebo-controlled study found evidence that a combination of the antioxidant vitamin E (400 IU daily) and vitamin C (1,000 mg daily) reduced incidence of pre-eclampsia. 5 Benefits were also seen in another study of this combination, 25 as well as a study using a mixture of numerous antioxidants along with other nutrients. 32 Additionally, a double-blind trial found potential preventive effects with the antioxidant substance lycopene (taken at 2 mg twice daily). 21 However, researchers caution that further study is necessary: Many other treatments have shown initial promise for preventing pre-eclampsia, but lost luster when subsequent studies were performed.
The most prominent of these once-promising substances include folate , magnesium , omega-3 fatty acids (fish oil), and zinc . 7-17,22,24 Furthermore, a large follow-up study of vitamin E combined with vitamin C failed to find any benefit, 29 and in a review of 10 studies involving a total of 6,533 subjects, antioxidant supplementation (of mostly vitamins E and C) during pregnancy did not reduce the risk of pre-eclampsia or any of its complications. 34 In addition, a high-quality randomized trial of 1,365 high-risk pregnant women found that daily supplementation with combination vitamin E (400 IU) and vitamin C (1,000 mg) through delivery was not associated with reduced risk of pre-eclampsia or other serious outcomes. 35
One study involving 235 pregnant women in Ecuador (average age 17.5 ) suggests that daily supplementation with 200 mg of coenzyme Q10 during the second half of pregnancy may reduce the risk of developing preeclampsia. 36 Though promising, the reliability of these results is in question because of low compliance with the supplements.
Results are mixed, yet somewhat positive on the potential benefits of arginine for treatments of pre-eclampsia. 26,27,30,37 In one study, 672 pregnant women at high-risk for pre-eclampsia were randomized to receive one of three treatments: arginine plus antioxidants, antioxidants alone, or placebo. 37 The women were followed until they gave birth. Those taking arginine plus antioxidants were at a lower risk of developing pre-eclampsia compared to the other two groups.
Evening primrose oil has failed to prove helpful, 20 as has a combination of vitamin C , vitamin E , and the drug allopurinol. 6 However, magnesium , taken by injection but not orally, appears to provide meaningful benefits. 18,19,23
One study failed to find N-acetyl cysteine (NAC) helpful for severe pre-eclampsia. 31

References

1 Atallah AN, Hofmeyr GJ, Duley L. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev . 2002;CD001059. Review.

2 Levine RJ, Hauth JC, Curet LB, et al. Trial of calcium to prevent pre-eclampsia. N Engl J Med. 1997;337:69-76.

3 Sanchez-Ramos L, Adair CD, Kaunitz AM, et al. Calcium supplementation in mild pre-eclampsia remote from term: a randomized double-blind clinical trial. Obstet Gynecol. 1995;85:915-918.

4 Hertz-Picciotto I, Schramm M, Watt-Morse M, et al. Patterns and determinants of blood lead during pregnancy. Am J Epidemiol. 2000;152:829-837.

5 Chappell LC, Seed PT, Briley AL, et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Lancet. 1999;354:810-816.

6 Gulmezoglu AM, Hofmeyr GJ, Oosthuisen MM. Antioxidants in the treatment of severe pre-eclampsia: an explanatory randomised controlled trial. Br J Obstet Gynaecol. 1997;104:689-696.

7 Sibai BM, Villar MA, Bray E. Magnesium supplementation during pregnancy: a double-blind randomized controlled clinical trial. Am J Obstet Gynecol. 1989;161:115-119.

8 Spatling L, Spatling G. Magnesium supplementation in pregnancy. A double-blind study. Br J Obstet Gynaecol. 1988;95:120-125.

9 Kovacs L, Molnar BG, Huhn E, et al. Magnesium substitution in pregnancy. A prospective, randomized double-blind study [translated from German]. Geburtsh Frauenheilk. 1988;48:595-600.

10 Jonsson B, Hauge B, Larsen MF, et al. Zinc supplementation during pregnancy: a double blind randomised controlled trial. Acta Obstet Gynecol Scand. 1996;75:725-729.

11 Hunt IF, Murphy NJ, Cleaver AE, et al. Zinc supplementation during pregnancy: effects on selected blood constituents and on progress and outcome of pregnancy in low-income women of Mexican descent. Am J Clin Nutr. 1984;40:508-521.

12 Mahomed K, James DK, Golding J, et al. Zinc supplementation during pregnancy: a double blind randomised controlled trial. BMJ. 1989;299:826-830.

13 Moutquin JM, Garner PR, Burrows RF, et al. Report of the Canadian Hypertension Society Consensus Conference: 2. Nonpharmacologic management and prevention of hypertensive disorders in pregnancy. CMAJ. 1997;157:907-919.

14 Salvig JD, Olsen SF, Secher NJ. Effects of fish oil supplementation in late pregnancy on blood pressure: a randomized controlled trial. Br J Obstet Gynaecol. 1996;103:529-533.

15 Onwude JL, Lilford RJ, Hjartardottir H, et al. A randomised double blind placebo controlled trial of fish oil in high risk pregnancy. Br J Obstet Gynaecol. 1995;102:95-100.

16 Bulstra-Ramakers MT, Huisjes HJ, Visser GH. The effects of 3 g eicosapentaenoic acid daily on recurrence of intrauterine growth retardation and pregnancy induced hypertension. Br J Obstet Gynaecol. 1995;102:123-126.

17 Olsen SF, Secher NJ. A possible preventive effect of low-dose fish oil on early delivery and pre-eclampsia: indications from a 50-year-old controlled trial. Br J Nutr. 1990;64:599-609.

18 The Magpie Trial Collaborative Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet. 2002;359:1877-1890.

19 Rudnicki M, Frolich A, Rasmussen WF, et al. The effect of magnesium on maternal blood pressure in pregnancy-induced hypertension. A randomized double-blind placebo-controlled trial. Acta Obstet Gynecol Scand. 1991;70:445-450.

20 Moodley J, Norman RJ. Attempts at dietary alteration of prostaglandin pathways in the management of pre-eclampsia. Prostaglandins Leukot Essent Fatty Acids. 1989;37:145-147.

21 Sharma JB, Kumar A, Kumar A, et al. Effect of lycopene on pre-eclampsia and intra-uterine growth retardation in primigravidas. Int J Gynaecol Obstet . 2003;81:257-262.

22 Sibai BM. Prevention of pre-eclampsia: a big disapointment. Am J Obstet Gynecol . 1998;179:1275-1278.

23 Livingston JC, Livingston LW, Ramsey R, et al. Magnesium sulfate in women with mild pre-eclampsia: a randomized controlled trial. Obstet Gynecol . 2003;101:217-220.

24 Sibai BM. Magnesium sulfate prophylaxis in pre-eclampsia: lessons learned from recent trials. Am J ObstetGynecol . 2004;190:1520-1526.

25 Beazley D, Ahokas R, Livingston J et al. Vitamin C and E supplementation in women at high risk for pre-eclampsia: A double-blind, placebo-controlled trial. Am J Obstet Gynecol . 2005;192:520-521.

26 Rytlewski K, Olszanecki R, Korbut R et al. Effects of prolonged oral supplementation with l-arginine on blood pressure and nitric oxide synthesis in pre-eclampsia. Eur J Clin Invest . 2005;35:32-37.

27 Staff AC, Berge L, Haugen G et al. Dietary supplementation with l-arginine or placebo in women with pre-eclampsia. Acta Obstet Gynecol Scand . 2004;83:103-107.

28 Villar J, Abdel-Aleem H, Merialdi M et al. World Health Organization randomized trial of calcium supplementation among low calcium intake pregnant women. Am J Obstet Gynecol . 2006;194:639-649.

29 Rumbold AR, Crowther CA, Haslam RR et al. Vitamins C and E and the risks of pre-eclampsia and perinatal complications. N Engl J Med . 2006;354:1796-1806.

30 Rytlewski K, Olszanecki R, Korbut R et al. Effects of prolonged oral supplementation with l-arginine on blood pressure and nitric oxide synthesis in pre-eclampsia. Eur J Clin Invest . 2005;35:32-37.

31 Roes EM, Raijmakers MT, Boo TM et al. Oral N-acetylcysteine administration does not stabilise the process of established severe pre-eclampsia. Eur J Obstet Gynecol Reprod Biol . 2005 Oct 19 [Epub ahead of print].

32 Rumiris D, Purwosunu Y, Wibowo N et al. Lower rate of pre-eclampsia after antioxidant supplementation in pregnant women with low antioxidant status. Hypertens Pregnancy. 2006;25:241-253.

33 Bergel E, Barros AJ. Effect of maternal calcium intake during pregnancy on children blood pressure: a systematic review of the literature. BMC Pediatr . 2007 Mar 26 [Epub ahead of print].

34 Rumbold A, Duley L, Crowther C, Haslam R. Antioxidants for preventing pre-eclampsia. Cochrane Database Syst Rev. 2008;CD004227.

35 Villar J, Purwar M, Merialdi M, et al. World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries. BJOG. 2009;116:780-788.

36 Teran E, Hernandez I, Nieto B, et al. Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia. Int J Gynaecol Obstet. 2009;105:43-5.

37 Vadillo-Ortega F, Perichart-Perera O, Espino S, et al. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial. BMJ. 2011;342:d2901.

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