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Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies

BMJ 2005; 330 doi: https://doi.org/10.1136/bmj.38380.674340.E0 (Published 10 March 2005) Cite this as: BMJ 2005;330:565

Pre-eclampsia risk factors include nutritional deficiencies

The pre-eclampsia community guideline (PRECOG) screening lists, and risk factor lists from Duckitt and Harrington,1 contain almost the same information as our medical student lectures from the late Professor Jimmy Walker in Dundee in the 1950s. In those days, pre-eclampsia usually occurred in first pregnancies. Have there been no advances in basic scientific knowledge over the past 50 years? It is a not a deterioration that multiparous women with a past history of pre-eclampsia now have a sevenfold increased risk of the condition in their next pregnancy?

The largest and newest risk factor, the presence of antiphospholipid antibodies, confers a nine fold increased relative risk of pre-eclampsia. This translates into an absolute risk of nearly 30%, as 2-3% of pregnant women are now afflicted. The female to male sex ratio for the antiphospholipid syndrome (APS)has become nine to one. The incidence of systemic lupus erythematosus (SLE) has increased from 1.51 /100,000 women in 1950 to 124.0 in 1995. Increasing use of hormonal contraceptives by younger and older women has increased dramatically the incidence of autoimmune diseases. Hormonal contraceptives or smoking induces immunoglobulin levels changes, elevations mostly, which may be transient or persistent if these precipitating factors are not avoided.2

It is alarming that essential nutrient deficiency risk factors, which should be a vital part of preconception and pregnancy care screening, are not even mentioned. Why only accept the importance of magnesium deficiency repletion as a last ditch emergency attempt to treat eclampsia? Magnesium deficiency significantly potentiates contractile responses to bradykinin, angiotensin II, serotonin, and prostaglandin F2 alpha and can cause spasms of umbilical and placental vasculature.3 What is so difficult about including red blood cell or sweat magnesium analyses in annual screening tests for women of reproductive age?

A decrease in maternal as well as umbilical plasma zinc concentrations was observed in pre-eclamptic women, and this decrease was statistically significant in severe pre-eclampsia.4 Elevated copper and lowered zinc levels were found in the placentas of pre-eclamptics.5 Mean activity of superoxide dismutase (SODase) in 45 pre-eclamptic placentas was significantly lower (3.89) compared to levels in placentas from normal pregnancies (6.75).6

Women with the lowest concentrations of toenail selenium had a 4.4- fold (95% CI 1.6-14.9) greater incidence of pre-eclampsia and more severe disease.7

Mineral deficiencies cause functional B vitamin deficiencies and block essential fatty acids pathways, allowing saturated fats to increase in cell walls. Ensuring a normal copper/zinc balance and using a red blood cell superoxidase dismutase test for copper status and a glutathione peroxidase function test for selenium status, along with other available screening tests can prevent pregnancy complications.8

There are now two studies finding larger babies in a malnourished population when pregnant women blind use of the UNICEF, WHO and the United Nations University recommended multi-supplement which includes zinc 15 mgs and copper 2 mgs. Both studies seem to be finding more perinatal deaths in the supplemented group.9,10 In my experience this daily dose of copper is too high and the dose of zinc is too low to obtain a good copper/zinc balance. Too much copper is toxic, especially to the fetus.

How can a woman be adequately screened to ensure a safe pre-eclampsia -free pregnancy if easily treatable essential nutrient deficiencies are not screened for and therefore not treated?

1 Duckitt K, Harrington D. Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 2005; 330: 565 (12 March), doi:10.1136/bmj.38380.674340.E0 (published 2 March 2005)

2 Grant ECG. Systemic Lupus erythematosus. Lancet 2001;358:586-7.

3 Altura BM, Altura BT, Carella A. Magnesium deficiency-induced spasms of umbilical vessels: relation to preeclampsia, hypertension, growth retardation. Science 1983;221:376-8.

4 Bassiouni BA, Foda AI, Rafei AA. Maternal and fetal plasma zinc in pre-eclampsia. Eur J Obstet Gynecol Reprod Biol. 1979; 9: 75-80.

5 Brophy MH, Harris NF, Crawford IL. Elevated copper and lowered zinc in the placentae of pre-eclamptics. Clin Chim Acta 1985;145:107-11.

6 Wiktor H, Kankofer M. Superoxide dismutase activity in normal and preeclamptic placentas. Ginekol Pol 1998;69:915-8.

7 Rayman MP, Bode P, Redman CW. Rayman MP, Bode P, Redman CW. Low selenium status is associated with the occurrence of the pregnancy disease preeclampsia in women from the United Kingdom. Am J Obstet Gynecol 2003; 189: 1343-9.

8 Grant ECG. Nutritional supplements to prevent pregnancy complications. http://bmj.com/cgi/eletters/329/7458/152#67502, 16 Jul 2004

9 Grant ECG. Monitored nutritional supplements to prevent pregnancy complications. http://bmj.com/cgi/eletters/329/7458/152#70176, 6 Aug 2004

10 Christian P, West KP, Khatry SK, et al. Effects of maternal micronutrient supplementation on fetal loss and infant mortality: a cluster-randomized trial in Nepal. Am J Clin Nutr. 2003;78:1194-202.

11 Orsin D, Vaidya A, Sherestha Y, et al. Effects of antenatal multiple micronutrient supplementation on birthweight and gestational duration in Nepal: double-blind, randomised controlled trial. Lancet 2005;365:955-62.

Competing interests: None declared

Competing interests: No competing interests

14 March 2005
Ellen C G Grant
physician and medical gynaecologist
Kingston-upon-Thames, KT2 7JU, UK