Advice about a healthy lifestyle

• The National Institute for Health and Clinical Excellence (NICE) looked at the evidence on lifestyle in women at risk of hypertensive disorders during pregnancy [National Collaborating Centre for Women's and Children's Health, 2010].
• Rest
• NICE reviewed the available evidence and concluded that there is insufficient evidence for the use of rest in any form to prevent hypertensive disease in pregnancy.
• Exercise
• NICE concluded that there is evidence from a Cochrane systematic review that exercise has no significant effect on reducing the incidence of pre-eclampsia.
• Work
• NICE found six studies on working hours and physical activity, including lifting heavy weights, and concluded that generally poor-quality evidence showed no effect.
• Weight
• NICE identified no evidence on maintaining a healthy weight during pregnancy.
• NICE concluded that advice on rest, exercise, and work for women at risk of hypertensive disorders of pregnancy should be the same as the advice given to healthy pregnant women in their guideline Antenatal care, routine care for the healthy pregnant woman [National Collaborating Centre for Women's and Children's Health, 2008].

Advice about moderate exercise

• This recommendation is based on expert advice from NICE [National Collaborating Centre for Women's and Children's Health, 2008].

Use of aspirin for women at high risk of pre-eclampsia

• The recommendations to use aspirin is based on expert advice from NICE [National Collaborating Centre for Women's and Children's Health, 2010]. NICE reviewed evidence from a Cochrane systematic review and a large meta-analysis of individual patient data and concluded that:
• The use of low-dose aspirin was consistent with a small risk reduction for pre-eclampsia, and there is a clear benefit in their defined high-risk groups.
• Moderate risk has been poorly defined in studies. However, the presence of two moderate risk factors would confer a greater risk that any risk factor considered individually.
• Data on the safety of aspirin in the doses used for the prevention of pre-eclampsia are sufficient.
• The recommendation to start aspirin at 12 weeks' gestation is based on expert advice from NICE, as this is the earliest gestational age for which there is available evidence concerning the use of aspirin for the prevention of pre-eclampsia [National Collaborating Centre for Women's and Children's Health, 2010].
• Most of the CKS expert reviewers recommended that aspirin should be given to girls younger than 16 years of age on specialist advice only.
• Some of our expert reviewers warned against prescribing aspirin to women with uncontrolled blood pressure. CKS recommends that in such women, it is best to seek specialist advice about whether or not to prescribe aspirin.

Women with thrombophilia

• NICE has stated that evidence on the association between thrombophilia and hypertensive disorders remains unclear. Only women with certain types of thrombophilia are at an increased risk of pre-eclampsia. These thrombophilias include women with hyperhomocysteinaemia, prothrombin heterozygosity, anticardiolipin antibodies, and Factor V Leiden heterozygosity. CKS therefore recommends that specialist advice is sought before prescribing aspirin.

Testing for proteinuria

• Expert opinion in the NICE guideline Antenatal care, routine care for the healthy pregnant woman states that when blood pressure is measured at each antenatal check, a urine sample should be tested at the same time for proteinuria [National Collaborating Centre for Women's and Children's Health, 2008]. NICE based this recommendation on evidence from a retrospective study of 53 women that found that those with proteinuria greater 500 mg per day had a high risk of pre-eclampsia [Stettler and Cunningham, 1992].
• Proteinuria is an important sign of pre-eclampsia after a gestation of 20 weeks. However, throughout pregnancy proteinuria may also be caused by an underlying medical condition [National Collaborating Centre for Women's and Children's Health, 2008].

Symptoms of pre-eclampsia

• These recommendations are based on expert advice from NICE [National Collaborating Centre for Women's and Children's Health, 2010] and three narrative reviews [Sadovsky, 2002; Duley et al, 2006; Young et al, 2010].
• A key recommendation from the 1998 Confidential Enquiry into Maternal Deaths that is accepted good clinical practice is that all women should receive antenatal education so that they are aware of the symptoms associated with pre-eclampsia (such as headache or epigastric pain), its importance, and the need to obtain medical advice [DH, 1998].

Measures not recommended for the prevention of hypertensive disorders of pregnancy

• A review of the literature for all of the following was undertaken by NICE [National Collaborating Centre for Women's and Children's Health, 2010].
• Nitric oxide
• NICE concluded that there is limited high-quality evidence from a Cochrane systematic review that there is no reduction in hypertensive disorders during pregnancy following the use of nitric oxide donors, such as glyceryl trinitrate.
• Progesterone
• NICE concluded that there is limited high-quality evidence from a Cochrane systematic review that there is no reduction in hypertensive disorders during pregnancy following the use of progesterone.
• Diuretics
• NICE concluded that there is limited high-quality evidence from a Cochrane systematic review that there is no reduction in hypertensive disorders during pregnancy following the use of diuretics.
• Low-molecular-weight heparin
• NICE reviewed the evidence from an open-label randomized controlled trial involving 80 women with the angiotensin converting enzyme DD genotype who had a history of pre-eclampsia [Mello et al, 2005]. This genotype is associated with thrombophilia and fetal loss. Although this study showed a clinically significant reduction in pre-eclampsia and its sequelae, NICE concluded that the study was of poor quality, and therefore the evidence is limited. NICE therefore have not recommended the use of low molecular weight heparin because of the risks associated with its use.
• Calcium
• NICE concluded that there is high quality evidence from a Cochrane systematic review that calcium supplementation reduces the risk of pre-eclampsia in women who have a low dietary intake of calcium (which does not generally apply to women in the UK). The benefits of calcium supplementation are greatest in women who are at high risk of pre-eclampsia. If calcium intake is known to be adequate then there is no statistically significant benefit. Therefore, NICE decided that routine calcium supplementation in the UK could not be justified.
• Magnesium
• NICE identified no evidence on the use of magnesium.
• Antioxidants
• NICE concluded that there is high-quality evidence from a Cochrane systematic review that there is no reduction in hypertensive disorders during pregnancy following the use of antioxidants. There is evidence from two randomized trials done since this review that there is no benefit from the use of antioxidants [Roberts et al, 2010; Xu et al, 2010]. One of the trials has suggested that there might be an increased risk of fetal loss and perinatal death associated with their use [Xu et al, 2010].
• Folic acid
• NICE found only poor-quality evidence from a large prospective cohort study involving 2951 women that investigated whether folic acid started early in the second trimester of pregnancy reduced the risk of pre-eclampsia. Although the results did suggest a possible benefit, NICE concluded that the results were likely to be confounded by other factors, including the use of other vitamins. There was no statistically significant evidence that folic acid alone reduced the risk of pre-eclampsia. Although folic acid is recommended in pregnancy for other reasons, it is not recommended for use to prevent hypertensive disorders of pregnancy.
• Fish oils
• NICE concluded that there is high-quality evidence from a Cochrane systematic review that there is no reduction in hypertensive disorders during pregnancy following the use of fish or algal oils.
• Garlic
• NICE concluded that there is limited good quality evidence from a Cochrane systematic review for the use of garlic to prevent pre-eclampsia, but increasing the intake of garlic is not recommended, as no significant effect was found.
• Dietary salt restriction
• NICE reviewed evidence from a randomized controlled trial involving 361 women and concluded that there is limited good-quality evidence that a low sodium diet does not prevent subsequent development of pre-eclampsia in women with weight gain and mild hypertension. However, although NICE does not recommend salt restriction to prevent pre-eclampsia, it stresses the importance of a healthy lifestyle and the importance of salt reduction in chronic hypertension.