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Preeclampsia (Holistic)

Preeclampsia (Holistic)

About This Condition

Mother-to-be? Protect yourself and your baby from the serious complications associated with this pregnancy problem. According to research or other evidence, the following self-care steps may be helpful.
  • Get routine checkups

    Visit your prenatal provider regularly to prevent and control preeclampsia

  • Consider calcium

    Reduce your risks by taking 1,200 to1,500 mg a day of this essential nutrient

  • Don’t skip the salt

    Use normal amounts of salt and drink more water to maintain normal circulation

About

About This Condition

Preeclampsia is defined as the combination of high blood pressure ( hypertension ), swelling ( edema ), and protein in the urine (albuminuria, proteinuria) developing after the 20th week of pregnancy .1 Preeclampsia ranges in severity from mild to severe; the mild form is sometimes called proteinuric pregnancy-induced hypertension2 or proteinuric gestational hypertension.3

Women with even mild preeclampsia must be monitored carefully by a healthcare professional. Hospitalization may be necessary to enable close observation.4

The cause of preeclampsia is unknown, although several factors have been shown to contribute.5 , 6 Preeclampsia is more common in women during their first pregnancy,7 as well as in women who are obese ,8 , 9 who have diabetes,10 or who have gestational hypertension .11 , 12 , 13 Women who have had preeclampsia during a previous pregnancy are also at increased risk.14 Preeclampsia has also been associated with calcium deficiencies,15 antioxidant deficiencies,16 , 17 , 18 older maternal age,19 and job stress.20 , 21 , 22

Symptoms

Symptoms, which typically appear after the 20th week of pregnancy , include swelling of the face and hands, visual disturbances, headache, and high blood pressure . In severe preeclampsia, symptoms are more pronounced. Jaundice may also be present. Severe preeclampsia may lead to seizures (eclampsia) and may cause death to both mother and fetus if left untreated.23 Like eclampsia, severe preeclampsia is a medical emergency requiring hospitalization.24 , 25

Healthy Lifestyle Tips

Regular prenatal care is essential for the prevention and early detection of preeclampsia.

Job stress (lack of control over work pace and the timing and frequency of breaks) may be detrimental, and reducing job stress may be beneficial in the prevention of preeclampsia.26 In a preliminary study, women exposed to high job stress were found to be at greater risk of developing preeclampsia and, to a lesser extent, gestational hypertension than were women exposed to low job stress. In this study, evaluation of job stress was based on scores assessing on-the-job psychological demand and decision-making latitude. High stress was defined as high psychological demand with low decision latitude, and low stress was defined as low-demand, high-latitude.27

For women with preeclampsia, obstetricians and midwives often recommend bed rest and lying on the left side; this position helps reduce edema and lower blood pressure by increasing urinary output.28However, a review of clinical trials concluded that bed rest can significantly worsen pregnancy-induced hypertension.29 Women with preeclampsia should discuss the pros and cons of bed rest with their doctors.

Eating Right

The right diet is the key to managing many diseases and to improving general quality of life. For this condition, scientific research has found benefit in the following healthy eating tips.

Recommendation Why
Don’t skip the salt
Use normal amounts of salt and drink more water to maintain normal circulation.

Unlike other conditions that cause high blood pressure , salt restriction and use of diuretics can worsen preeclampsia by reducing blood flow to the kidneys and placenta.30 In preeclampsia, unrestricted use of salt and an increased consumption of water are needed to maintain normal blood volume and circulation to the placenta.31

Avoid trans fats
Diets high in trans fatty acids appear to increase preeclampsia risk, so avoiding margarine and deep-fried foods may decrease your risk.

Data from one preliminary study suggest diets high in trans fatty acids are associated with an increased risk of preeclampsia.32 Trans fatty acids are found in foods that contain partially hydrogenated vegetable oils, such as margarine. Foods that have been deep-fried (e.g., French fries) are also rich sources of trans fatty acids.

Supplements

What Are Star Ratings?

Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.

For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.

2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

Supplement Why
3 Stars
Calcium
1,200 to 1,500 mg daily
An analysis of double-blind trials found calcium supplementation to be highly effective in preventing preeclampsia.

Calcium deficiency has been associated with preeclampsia.33 In numerous controlled trials, oral calcium supplementation has been studied as a possible preventive measure.34 35 36 37 While most trials have found a significant reduction in the incidence of preeclampsia with calcium supplementation,38 39 40 41 42 43 One study reported that calcium supplementation reduced both the severity of preeclampsia and the mortality rate in the infants.44

An analysis of double-blind trials46 found calcium supplementation to be highly effective in preventing preeclampsia. However, a large and well-designed double-blind trial and a critical analysis of six double-blind trials concluded that calcium supplementation did not reduce the risk of preeclampsia in healthy women at low risk for preeclampsia.45 For healthy, high-risk (in other words, calcium deficient) women, however, the data show a clear and statistically significant beneficial effect of calcium supplementation in reducing the risk of preeclampsia.46 47 48 49 50 51 52 53 54 55 56 57 58 59

The National Institutes of Health recommends an intake of 1,200 to 1,500 mg of elemental calcium daily during normal pregnancy.60 In women at risk of preeclampsia, most trials showing reduced incidence have used 2,000 mg of supplemental calcium per day.61 Nonetheless, many doctors continue to suggest amounts no higher than 1,500 mg per day.

2 Stars
Coenzyme Q10
200 mg per day
In a double-blind study at women who were at high risk of developing preeclampsia, supplementing with coenzyme Q10 reduced the incidence of preeclampsia by 44%.

Pregnant women with preeclampsia have significantly lower plasma coenzyme Q10 levels, when compared with women with healthy pregnancies. In a double-blind study at women who were at high risk of developing preeclampsia, supplementing with coenzyme Q10 reduced the incidence of preeclampsia by 44%. The amount used was 200 mg per day; treatment was begun during the twentieth week of pregnancy and continued until delivery.62

2 Stars
Folic Acid
5 mg daily
Supplementing with folic acid and vitamin B6 may lower homocysteine levels. Elevated homocysteine damages the lining of blood vessels and can lead to the preeclamptic symptoms.

Women with preeclampsia have been shown to have elevated blood levels of homocysteine .63 , 64 , 65 , 66 Research indicates elevated homocysteine occurs prior to the onset of preeclampsia.67 Elevated homocysteine damages the lining of blood vessels,68 , 69 , 70 , 71 , 72 , 73 , 74 which can lead to the preeclamptic signs of elevated blood pressure , swelling, and protein in the urine.75

In one preliminary trial, women with a previous pregnancy complicated by preeclampsia and high homocysteine supplemented with 5 mg of folic acid and 250 mg of vitamin B6 per day, successfully lowering homocysteine levels.76 In another trial studying the effect of vitamin B6 on preeclampsia incidence, supplementation with 5 mg of vitamin B6 twice per day significantly reduced the incidence of preeclampsia. Women in that study were not, however, evaluated for homocysteine levels.77 In fact, no studies have yet determined whether lowering elevated homocysteine reduces the incidence or severity of preeclampsia. Nevertheless, despite a lack of proof that elevated homocysteine levels cause preeclampsia, many doctors believe that pregnant women with elevated homocysteine should attempt to reduce those levels to normal.
2 Stars
Vitamin C and Vitamin E
1,000 mg daily vitamin C with 400 IU vitamin E
  
1 Star
Fish Oil
Refer to label instructions
Fish oil supplementation may lower the incidence of preeclampsia.

Fish oil supplementation has been proposed to lower the incidence of preeclampsia.78 , 79 However, controlled clinical trials suggest that fish oil does not reduce symptoms80 or protect against preeclampsia.81 , 82

1 Star
Magnesium
Refer to label instructions
Magnesium supplementation has been shown to reduce the incidence of preeclampsia in high-risk women in one trial.

Magnesium deficiency has been implicated as a possible cause of preeclampsia.83 , 84 , 85 , 86 , 87 Magnesium supplementation has been shown to reduce the incidence of preeclampsia in high-risk women in one trial,88 but not in another double-blind trial.89

1 Star
Vitamin B2
Refer to label instructions
Women who are deficient in vitamin B2 (riboflavin) are more likely to develop preeclampsia than women with normal levels. Supplementation may correct a deficiency.

Women who are deficient in vitamin B2 (riboflavin) are more likely to develop preeclampsia than women with normal vitamin B2 levels.90 These results were observed in a developing country, where vitamin B2 deficiencies are more common than in the United States. Nevertheless, insufficient vitamin B2 may contribute to the abnormalities underlying the disease process.
1 Star
Vitamin B6
Refer to label instructions
Supplementing with vitamin B6 and folic acid may lower homocysteine levels. Elevated homocysteine damages the lining of blood vessels and can lead to the preeclamptic symptoms.

Women with preeclampsia have been shown to have elevated blood levels of homocysteine .91 , 92 , 93 , 94 Research indicates elevated homocysteine occurs prior to the onset of preeclampsia.95 Elevated homocysteine damages the lining of blood vessels,96 , 97 , 98 , 99 , 100 , 101 , 102 which can lead to the preeclamptic signs of elevated blood pressure , swelling, and protein in the urine.103

In one preliminary trial, women with a previous pregnancy complicated by preeclampsia and high homocysteine supplemented with 5 mg of folic acid and 250 mg of vitamin B6 per day, successfully lowering homocysteine levels.104 In another trial studying the effect of vitamin B6 on preeclampsia incidence, supplementation with 5 mg of vitamin B6 twice per day significantly reduced the incidence of preeclampsia. Women in that study were not, however, evaluated for homocysteine levels.105 In fact, no studies have yet determined whether lowering elevated homocysteine reduces the incidence or severity of preeclampsia. Nevertheless, despite a lack of proof that elevated homocysteine levels cause preeclampsia, many doctors believe that pregnant women with elevated homocysteine should attempt to reduce those levels to normal.

References

1. Myatt L, Miodovnik M. Prediction of preeclampsia. Semin Perinatol 1999;23:45–57.

2. Smith GN, Walker M, Tessier JL, Millar KG. Increased incidence of preeclampsia in women conceiving by intrauterine insemination with donor versus partner sperm for treatment of primary infertility. Am J Obstet Gynecol 1997;177:455–8.

3. Rey E, LeLorier J, Burgess E, et al. Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacologic treatment of hypertensive disorders in pregnancy. CMAJ 1997;157:1245–54.

4. Rath W Z. Treatment of hypertensive diseases in pregnancy—general recommendations and long-term oral therapy. Geburtshilfe Neonatol 1997;201:240–6 [in German].

5. Myatt L, Miodovnik M. Prediction of preeclampsia. Semin Perinatol 1999;23:45–57.

6. Sibai B. Prevention of preeclampsia: a big disappointment. Am J Obstet Gynecol 1998;179:1275–8 [review].

7. Mounier-Vehier C, Equine O, Valat-Rigot AS, et al. Hypertensive syndromes in pregnancy. Physiopathology, definition and fetomaternal complications. Presse Med 1999;28:880–5 [in French].

8. Mounier-Vehier C, Equine O, Valat-Rigot AS, et al. Hypertensive syndromes in pregnancy. Physiopathology, definition and fetomaternal complications. Presse Med 1999;28:880–5 [in French].

9. Sibai BM, Ewell M, Levine RJ, et al. Risk factors associated with preeclampsia in healthy nulliparous women. The Calcium for Preeclampsia Prevention (CPEP) Study Group. Am J Obstet Gynecol 1997;177:1003–10.

10. Persson B, Hanson U. Neonatal morbidities in gestational diabetes mellitus. Diabetes Care 1998;Suppl 2:B79–84.

11. Saudan P, Brown MA, Buddle ML, Jones M. Does gestational hypertension become pre-eclampsia? Br J Obstet Gynaecol 1998;105:1177–84.

12. Myatt L, Miodovnik M. Prediction of preeclampsia. Semin Perinatol 1999;23:45–57.

13. Sibai BM, Ewell M, Levine RJ, et al. Risk factors associated with preeclampsia in healthy nulliparous women. The Calcium for Preeclampsia Prevention (CPEP) Study Group. Am J Obstet Gynecol 1997;177:1003–10.

14. Myatt L, Miodovnik M. Prediction of preeclampsia. Semin Perinatol 1999;23:45–57.

15. Hojo M, August P. Calcium Metabolism in Preeclampsia: Supplementation may help. Medscape Womens Health 1997;2:5.

16. Mikhail MS, Anyaegbunam A, Garfinkel D, et al. Preeclampsia and antioxidant nutrients: decreased plasma levels of reduced ascorbic acid, alpha-tocopherol and beta carotene in women with preeclampsia. Am J Obstet Gynecol 1994;171:150–7.

17. Gulmezoglu AM, Hofmeyr GJ, Oosthuisen MM. Antioxidants in the treatment of severe pre-eclampsia: an explanatory randomised controlled trial. Br J Obstet Gynaecol 1997;104:689–96.

18. Valsecchi L, Fausto A, Grazioli V. Severe preeclampsia and antioxidant nutrients. Am J Obstet Gynecol 1995;173:673 [letter].

19. Bianco A, Stone J, Lynch L, et al. Pregnancy outcome at age 40 and older. Obstet Gynecol 1996;87:917–22.

20. Marcoux S, Berube S, Brisson C, Mondor M. Job strain and pregnancy-induced hypertension. Epidemiology 1999;10:376–82.

21. Wergeland E, Strand K. Work pace control and pregnancy health in a population-based sample of employed women in Norway. Scand J Work Environ Health 1998;24:206–12.

22. Mounier-Vehier C, Equine O, Valat-Rigot AS, et al. Hypertensive syndromes in pregnancy. Physiopathology, definition and fetomaternal complications. Presse Med 1999;28:880–5 [in French].

23. Rath W Z. Treatment of hypertensive diseases in pregnancy—general recommendations and long-term oral therapy. Geburtshilfe Neonatol 1997;201:240–6 [in German].

24. Rey E, LeLorier J, Burgess E, et al. Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacologic treatment of hypertensive disorders in pregnancy. CMAJ 1997;157:1245–54.

25. Sibai BM, Frangieh AY. Management of severe preeclampsia. Curr Opin Obstet Gynecol 1996;8(2):110–3.

26. Wergeland E, Strand K. Work pace control and pregnancy health in a population-based sample of employed women in Norway. Scand J Work Environ Health 1998;24:206–12.

27. Marcoux S, Berube S, Brisson C, Mondor M. Job strain and pregnancy-induced hypertension. Epidemiology 1999;10:376–82.

28. Katz VL, Ryder RM, Cefalo RC, et al. A comparison of bed rest and immersion for treating the edema of pregnancy. Obstet Gynecol 1990;75:147–51.

29. Allen C, Glasziou P, Del Mar C. Bed rest: a potentially harmful treatment needing more careful evaluation. Lancet 1999;354:1229–33 [review].

30. Franx A, Steegers EA, de Boo T, et al. Sodium-blood pressure interrelationship in pregnancy. J Hum Hypertens 1999;13:159–66.

31. 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;157:907–19.

32. Williams MA, King IB, Sorensen TK, et al. Risk of preeclampsia in relation to elaidic acid (trans fatty acid) in maternal erythrocytes. Gynecol Obstet Invest 1998;46:84–7.

33. 33. Hojo M, August P. Calcium metabolism in normal and hypertensive pregnancy. *Semin Nephrol* 1995;15:504–11 [review].

34. Hojo M, August P. Calcium Metabolism in Preeclampsia: Supplementation may help. *Medscape Womens Health* 1997;2:5.

35. 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;157:907–19.

36. Levine RJ, Hauth JC, Curet LB, et al. Trial of calcium to prevent preeclampsia. *N Engl J Med* 1997;337:69–76.

37. Belizan JM, Villar J, Gonzalez, et al. Calcium supplementation to prevent hypertensive disorders of pregnancy. *N Engl J Med* 1991;325:1399–405.

38. Hojo M, August P. Calcium Metabolism in Preeclampsia: Supplementation may help. *Medscape Womens Health* 1997;2:5.

39. 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;157:907–19.

40. Crowther CA, Hiller JE, Pridmore B, et al. Calcium supplementation in nulliparous women for the prevention of pregnancy-induced hypertension, preeclampsia, and preterm birth: an Australian randomized trial. FRACOG and the ACT study group. *Aust N Z J Obstet Gynaecol* 1999;39:12–8.

41. Bucher HC, Guyatt GH, Cook RJ, et al. Effect of calcium supplementation on pregnancy-induced hypertension and preeclampsia: a meta-analysis of randomized controlled trials. *JAMA* 1996;275:1113–7.

42. Belizan JM, Villar J, Gonzalez, et al. Calcium supplementation to prevent hypertensive disorders of pregnancy. *N Engl J Med* 1991;325:1399–405.

43. Herrera JA, Arevalo-Herrera M, Herrera S. Prevention of preeclampsia by linoleic acid and calcium supplementation: a randomized controlled trial. *Obstet Gynecol* 1998;91:585–90.

44. Levine RJ, Hauth JC, Curet LB, et al. Trial of calcium to prevent preeclampsia. *N Engl J Med* 1997;337:69–76.

45. 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;194:639–49.

46. 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;194:639–49.

47. Bucher HC, Guyatt GH, Cook RJ, et al. Effect of calcium supplementation on pregnancy-induced hypertension and preeclampsia: a meta-analysis of randomized controlled trials. *JAMA* 1996;275:1113–7.

48. Levine RJ, Hauth JC, Curet LB, et al. Trial of calcium to prevent preeclampsia. *N Engl J Med* 1997;337:69–76.

49. Sibai BM. Prevention of preeclampsia: a big disappointment. *Am J Obstet Gynecol* 1998;179:1275–8.

50. Levine RJ, Hauth JC, Curet LB, et al. Trial of calcium to prevent preeclampsia. *N Engl J Med* 1997;337:69–76.

51. Lopez-Jaramillo P, Narvaez M, Weigel RM, Yepez R. Calcium supplementation reduces the risk of pregnancy-induced hypertension in an Andes population. *Br J Obstet Gynaecol* 1989;96:648–55.

52. Lopez-Jaramillo P, Narvaez M, Felix C, Lopez A. Dietary calcium supplementation and prevention of pregnancy hypertension. *Lancet* 1990;335:293. [letter]

53. Villar J, Repke JT. Calcium supplementation during pregnancy may reduce preterm delivery in high-risk populations. *Am J Obstet Gynecol* 1990;163:1124–31.

54. Belizan JM, Villar J, Gonzalez L. Calcium supplementation to prevent hypertensive disorders of pregnancy. N Engl J Med 1991;325:1399–405.

55. Belizan JM, Villar J, Gonzalez L. Calcium supplementation to prevent hypertensive disorders of pregnancy. *N Engl J Med* 1991;325:1399–405.

56. Sanchez-Ramos L, Briones DK, Kaunitz AM, et al. Prevention of pregnancy-induced hypertension by calcium supplementation in angiotensin II-sensitive patients. *Obstet Gynecol* 1994;84:349–53.

57. DerSimonian R, Levine RJ. Resolving discrepancies between a meta-analysis and a subsequent large controlled trial. *JAMA* 1999;282:664–70 [review].

58. Ritchie LD, King JC. Dietary calcium and pregnancy-induced hypertension: is there a relation? *Am J Clin Nutr* 2000;71(5 Suppl):1371–4S [review].

59. Villar J, Belizan JM. Same nutrient, different hypotheses: disparities in trials of calcium supplementation during pregnancy. *Am J Clin Nutr* 2000;71(5 Suppl):1375–9S [review].

60. NIH Consensus conference. Optimal calcium intake. NIH Consensus Development Panel on Optimal Calcium Intake. *JAMA* 1994;272(24):1942 [review].

61. 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;157:907–19.

62. 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.

63. Leeda M, Riyazi N, de Vries JI, et al. Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. Am J Obstet Gynecol 1998;179:135–9.

64. Powers RW, Evans RW, Majors AK, et al. Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation. Am J Obstet Gynecol 1998;179:1605–11.

65. Rajkovic A, Catalano PM, Malinow MR. Elevated homocyst(e)ine levels with preeclampsia. Obstet Gynecol 1997;90:168–71.

66. Laivuori H, Kaaja R, Turpeinen U, et al. Plasma homocysteine levels elevated and inversely related to insulin sensitivity in preeclampsia. Obstet Gynecol 1999;93:489–93.

67. Sorensen TK, Malinow MR, Williams MA, et al. Elevated second-trimester serum homocyst(e)ine levels and subsequent risk of preeclampsia. Gynecol Obstet Invest 1999;48:98–103.

68. Powers RW, Evans RW, Majors AK, et al. Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation. Am J Obstet Gynecol 1998;179:1605–11.

69. Ray JG, Laskin CA. Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: A systematic review. Placenta 1999;20:519–29 [review].

70. Sorensen TK, Malinow MR, Williams MA, et al. Elevated second-trimester serum homocyst(e)ine levels and subsequent risk of preeclampsia. Gynecol Obstet Invest 1999;48:98–103.

71. Roberts JM. Endothelial dysfunction in preeclampsia. Semin Reprod Endocrinol 1998;16:5–15.

72. Hayman R, Brockelsby J, Kenny L, Baker P. Preeclampsia: the endothelium, circulating factor(s) and vascular endothelial growth factor. J Soc Gynecol Investig 1999;6:3–10.

73. Lyall F, Greer IA. The vascular endothelium in normal pregnancy and pre-eclampsia. Rev Reprod 1996;1:107–16.

74. Roberts JM, Redman CWG. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet 1994;341:1447–54.

75. Taylor RN, de Groot CJ, Cho YK, Lim KH. Circulating factors as markers and mediators of endothelial cell dysfunction in preeclampsia. Semin Reprod Endocrinol 1998;16:17–31.

76. Leeda M, Riyazi N, de Vries JI, et al. Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. Am J Obstet Gynecol 1998;179:135–9.

77. Wachstein M, Graffeo LW. Influence of Vitamin B6 on the incidence of preeclampsia. Obstet Gynecol 1956;8:177–80.

78. Sibai BM. Prevention of preeclampsia: A big disappointment. Am J Obstet Gynecol 1998;179:1275–8 [review].

79. Williams MA, Zingheim RW, King IB, Zebelman AM. Omega-3 fatty acids in maternal erythrocytes and risk for preeclampsia. Epidemiology 1995;6:232–7.

80. Laivuori H, Hovatta O, Viinikka L, Ylikorkala O. Dietary supplementation with primrose oil or fish oil does not change urinary excretion of prostacyclin and thromboxane metabolites in pre-eclamptic women. Prostaglandins Leukot Essent Fatty Acids 1993;49:691–4.

81. Onwude JL, Lilford RJ, Hjartardottier H, et. al. A randomised double blind placebo controlled trial of fish oil in high risk pregnancy. Br J Obstet Gynaecol 1995;109:95–100.

82. Salvig JD, Olsen SF, Secher NJ. Effects of fish oil supplementation in late pregnancy on blood pressure: a randomised controlled trial. Br J Obstet Gynaecol 1996;103:529–33.

83. Wynn A, Wynn M. Magnesium and other nutrient deficiencies as possible causes of hypertension and low birth weight. Nutr Health 1988;6:69–88.

84. Spatling L, Spatling G. Magnesium supplementation in pregnancy: a double-blind study. Br J Obstet Gynaecol 1988;950:120–5.

85. Sibai BM, Villar MA, Bray E. Magnesium supplementation during pregnancy: a double-blind randomized controlled clinical trial. Am J Obstet Gynecol 1989;161:115–9.

86. Standley CA, Whitty JE, Mason BA, Cotton DB. Serum ionized magnesium levels in normal and preeclamptic gestation. Obstet Gynecol 1997;89:24–7.

87. Handwerker SM, Altura BT, Altura BM. Ionized serum magnesium and potassium levels in pregnant women with preeclampsia and eclampsia. J Reprod Med 1995;40:201–8.

88. Conradt A, Weidinger H, Algayer G. Magnesium deficiency, a possible cause of pre-eclampsia: reduction of frequency of premature rupture of membranes and premature or small-for-date deliveries after magnesium supplementation. J Am Coll Nutr 1985;4:321.

89. Spatling L, Spatling G. Magnesium supplementation in pregnancy: a double-blind study. Br J Obstet Gynaecol 1988;950:120–5.

90. Wacker J, Fruhauf J, Schulz M, et al. Riboflavin deficiency and preeclampsia. Obstet Gynecol 2000;96:38–44.

91. Leeda M, Riyazi N, de Vries JI, et al. Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. Am J Obstet Gynecol 1998;179:135–9.

92. Powers RW, Evans RW, Majors AK, et al. Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation. Am J Obstet Gynecol 1998;179:1605–11.

93. Rajkovic A, Catalano PM, Malinow MR. Elevated homocyst(e)ine levels with preeclampsia. Obstet Gynecol 1997;90:168–71.

94. Laivuori H, Kaaja R, Turpeinen U, et al. Plasma homocysteine levels elevated and inversely related to insulin sensitivity in preeclampsia. Obstet Gynecol 1999;93:489–93.

95. Sorensen TK, Malinow MR, Williams MA, et al. Elevated second-trimester serum homocyst(e)ine levels and subsequent risk of preeclampsia. Gynecol Obstet Invest 1999;48:98–103.

96. Powers RW, Evans RW, Majors AK, et al. Plasma homocysteine concentration is increased in preeclampsia and is associated with evidence of endothelial activation. Am J Obstet Gynecol 1998;179:1605–11.

97. Ray JG, Laskin CA. Folic acid and homocyst(e)ine metabolic defects and the risk of placental abruption, pre-eclampsia and spontaneous pregnancy loss: A systematic review. Placenta 1999;20:519–29 [review].

98. Sorensen TK, Malinow MR, Williams MA, et al. Elevated second-trimester serum homocyst(e)ine levels and subsequent risk of preeclampsia. Gynecol Obstet Invest 1999;48:98–103.

99. Roberts JM. Endothelial dysfunction in preeclampsia. Semin Reprod Endocrinol 1998;16:5–15.

100. Hayman R, Brockelsby J, Kenny L, Baker P. Preeclampsia: the endothelium, circulating factor(s) and vascular endothelial growth factor. J Soc Gynecol Investig 1999;6:3–10.

101. Lyall F, Greer IA. The vascular endothelium in normal pregnancy and pre-eclampsia. Rev Reprod 1996;1:107–16.

102. Roberts JM, Redman CWG. Pre-eclampsia: more than pregnancy-induced hypertension. Lancet 1994;341:1447–54.

103. Taylor RN, de Groot CJ, Cho YK, Lim KH. Circulating factors as markers and mediators of endothelial cell dysfunction in preeclampsia. Semin Reprod Endocrinol 1998;16:17–31.

104. Leeda M, Riyazi N, de Vries JI, et al. Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. Am J Obstet Gynecol 1998;179:135–9.

105. Wachstein M, Graffeo LW. Influence of Vitamin B6 on the incidence of preeclampsia. Obstet Gynecol 1956;8:177–80.

106. Lazebnik N, Kuhnert BR, Kuhnert PM. Zinc, cadmium, and hypertension in parturient women. J Obstet Gynecol 1989;161:437–40.

107. Cherry FF, Bennett EA, Bazzano GS, et al. Plasma zinc in hypertension/toxemia and other reproductive variables in adolescent pregnancy. Am J Clin Nutr 1981;34:2367–75.

108. Simmer K, Iles CA, James C, Thompson RP. Are iron-folate supplements harmful? Am J Clin Nutr 1987;45:122–5.

109. 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;40:508–21.

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