Methods of prediction and prevention of pre-eclampsia: systematic reviews of accuracy and effectiveness literature with economic modelling.

OBJECTIVES: To investigate the accuracy of predictive tests for pre-eclampsia and the effectiveness of preventative interventions for pre-eclampsia. Also to assess the cost-effectiveness of strategies (test-intervention combinations) to predict and prevent pre-eclampsia. DATA SOURCES: Major electronic databases were searched to January 2005 at least. REVIEW METHODS: Systematic reviews were carried out for test accuracy and effectiveness. Quality assessment was carried out using standard tools. For test accuracy, meta-analyses used a bivariate approach. Effectiveness reviews were conducted under the auspices of the Cochrane Pregnancy and Childbirth Group and used standard Cochrane review methods. The economic evaluation was from an NHS perspective and used a decision tree model. RESULTS: For the 27 tests reviewed, the quality of included studies was generally poor. Some tests appeared to have high specificity, but at the expense of compromised sensitivity. Tests that reached specificities above 90% were body mass index greater than 34, alpha-foetoprotein and uterine artery Doppler (bilateral notching). The only Doppler test with a sensitivity of over 60% was resistance index and combinations of indices. A few tests not commonly found in routine practice, such as kallikreinuria and SDS-PAGE proteinuria, seemed to offer the promise of high sensitivity, without compromising specificity, but these would require further investigation. For the 16 effectiveness reviews, the quality of included studies was variable. The largest review was of antiplatelet agents, primarily low-dose aspirin, and included 51 trials (36,500 women). This was the only review where the intervention was shown to prevent both pre-eclampsia and its consequences for the baby. Calcium supplementation also reduced the risk of pre-eclampsia, but with some uncertainty about the impact on outcomes for the baby. The only other intervention associated with a reduction in RR of pre-eclampsia was rest at home, with or without a nutritional supplement, for women with normal blood pressure. However, this review included just two small trials and its results should be interpreted with caution. The cost of most of the tests was modest, ranging from 5 pounds for blood tests such as serum uric acid to approximately 20 pounds for Doppler tests. Similarly, the cost of most interventions was also modest. In contrast, the best estimate of additional average cost associated with an average case of pre-eclampsia was high at approximately 9000 pounds. The results of the modelling revealed that prior testing with the test accuracy sensitivities and specificities identified appeared to offer little as a way of improving cost-effectiveness. Based on the evidence reviewed, none of the tests appeared sufficiently accurate to be clinically useful and the results of the model favoured no-test/treat-all strategies. Rest at home without any initial testing appeared to be the most cost-effective 'test-treatment' combination. Calcium supplementation to all women, without any initial testing, appeared to be the second most cost-effective. The economic model provided little support that any form of Doppler test has sufficiently high sensitivity and specificity to be cost-effective for the early identification of pre-eclampsia. It also suggested that the pattern of cost-effectiveness was no different in high-risk mothers than the low-risk mothers considered in the base case. CONCLUSIONS: The tests evaluated are not sufficiently accurate, in our opinion, to suggest their routine use in clinical practice. Calcium and antiplatelet agents, primarily low-dose aspirin, were the interventions shown to prevent pre-eclampsia. The most cost-effective approach to reducing pre-eclampsia is likely to be the provision of an effective, affordable and safe intervention applied to all mothers without prior testing to assess levels of risk. It is probably premature to suggest the implementation of a treat-all intervention strategy at present, however the feasibility and acceptability of this to women could be explored. Rigorous evaluation is needed of tests with modest cost whose initial assessments suggest that they may have high levels of both sensitivity and specificity. Similarly, there is a need for high-quality, adequately powered randomised controlled trials to investigate whether interventions such as advice to rest are indeed effective in reducing pre-eclampsia. In future, an economic model should be developed that considers not just pre-eclampsia, but other related outcomes, particularly those relevant to the infant such as perinatal death, preterm birth and small for gestational age. Such a modelling project should make provision for primary data collection on the safety of interventions and their associated costs.

Antioxidants for preventing pre-eclampsia.

BACKGROUND: Oxidative stress has been proposed as a key factor involved in the development of pre-eclampsia. Supplementing women with antioxidants during pregnancy may help to counteract oxidative stress and thereby prevent or delay the onset of pre-eclampsia. OBJECTIVES: To determine the effectiveness and safety of any antioxidant supplementation during pregnancy and the risk of developing pre-eclampsia and its related complications. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 3), MEDLINE (1950 to October 2007) and Current Contents (1998 to August 2004). SELECTION CRITERIA: All randomised trials comparing one or more antioxidants with either placebo or no antioxidants during pregnancy for the prevention of pre-eclampsia, and trials comparing one or more antioxidants with another, or with other interventions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and trial quality and extracted data. MAIN RESULTS: Ten trials, involving 6533 women, were included in this review, five trials were rated high quality. For the majority of trials, the antioxidant assessed was combined vitamin C and E therapy. There was no significant difference between antioxidant and control groups for the relative risk (RR) of pre-eclampsia (RR 0.73, 95% confidence intervals (CI) 0.51 to 1.06; nine trials, 5446 women) or any other primary outcome: severe pre-eclampsia (RR 1.25, 95% CI 0.89 to 1.76; two trials, 2495 women), preterm birth (before 37 weeks) (RR 1.10, 95% CI 0.99 to 1.22; five trials, 5198 women), small-for-gestational-age infants (RR 0.83, 95% CI 0.62 to 1.11; five trials, 5271 babies) or any baby death (RR 1.12, 95% CI 0.81 to 1.53; four trials, 5144 babies). Women allocated antioxidants were more likely to self-report abdominal pain late in pregnancy (RR 1.61, 95% CI 1.11 to 2.34; one trial, 1745 women), require antihypertensive therapy (RR 1.77, 95% CI 1.22 to 2.57; two trials, 4272 women) and require an antenatal hospital admission for hypertension (RR 1.54, 95% CI 1.00 to 2.39; one trial, 1877 women). However, for the latter two outcomes, this was not clearly reflected in an increase in any other hypertensive complications. AUTHORS' CONCLUSIONS: Evidence from this review does not support routine antioxidant supplementation during pregnancy to reduce the risk of pre-eclampsia and other serious complications in pregnancy.

Dietary calcium supplementation for prevention of pre-eclampsia and related problems: a systematic review and commentary.

BACKGROUND: Calcium supplementation during pregnancy may reduce the risk of hypertensive disorders of pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Central Register of Controlled Trials (March 2006). SELECTION CRITERIA: Randomised trials comparing at least 1 g of calcium daily during pregnancy with placebo. Eligibility and trial quality were assessed. DATA COLLECTION AND ANALYSIS: Data were extracted and analysed using Review Manager software. MAIN RESULTS: Twelve studies (15,528 women) were included, all of good quality. Most women were at low risk and had low dietary calcium. High blood pressure was reduced with calcium supplementation rather than placebo (11 trials, 14,946 women: relative risk [RR] random effects model 0.70; 95% CI 0.57-0.86), as was pre-eclampsia (12 trials, 15,206 women: RR 0.48; 95% CI 0.33-0.69). The effect was greatest for women at high risk (five trials, 587 women: RR 0.22; 95% CI 0.12-0.42) and for those with low baseline calcium intake (seven trials, 10,154 women: RR 0.36; 95% CI 0.18-0.70). There was heterogeneity, with less effect in the larger trials. The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women: RR 0.80; 95% CI 0.65-0.97). The syndrome of haemolysis, elevated liver enzymes and low platelets was increased (two trials, 12,901 women: RR 2.67; 95% CI 1.05-6.82). There was no overall effect on the risk of preterm birth or stillbirth or death before discharge from hospital. CONCLUSIONS: Calcium supplementation appears to reduce the risk of pre-eclampsia and to reduce the rare occurrence of the composite outcome 'maternal death or serious morbidity'. There were no other clear benefits or harms. COMMENTARY: We present the hypothesis that adequate dietary calcium before and in early pregnancy may be needed to prevent the underlying pathology responsible for pre-eclampsia. We suggest that the research agenda be redirected towards calcium supplementation at a community level.

Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

BACKGROUND: Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia through a number of mechanisms, and may help to prevent preterm labour. OBJECTIVES: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2005, Issue 4), and contacted study authors. SELECTION CRITERIA: Randomised trials comparing at least one gram daily of calcium during pregnancy with placebo. DATA COLLECTION AND ANALYSIS: We assessed eligibility and trial quality, extracted and double-entered data. MAIN RESULTS: Twelve studies of good quality were included. The risk of high blood pressure was reduced with calcium supplementation rather than placebo (11 trials, 14,946 women: relative risk (RR) 0.70, 95% confidence interval (CI) 0.57 to 0.86). There was also a reduction in the risk of pre-eclampsia associated with calcium supplementation (12 trials, 15,206 women: RR 0.48, 95% CI 0.33 to 0.69). The effect was greatest for high-risk women (5 trials, 587 women: RR 0.22, 95% CI 0.12 to 0.42), and those with low baseline calcium intake (7 trials, 10,154 women: RR 0.36, 95% CI 0.18 to 0.70). The composite outcome maternal death or serious morbidity was reduced (4 trials, 9732 women; RR 0.80, 0.65 to 0.97). Almost all the women in these trials were low risk and had a low calcium diet. Maternal deaths were reported in only one trial. One death occurred in the calcium group and six in the placebo group, a difference which was not statistically significant (RR 0.17, 95% CI 0.02 to 1.39). There was no overall effect on the risk of preterm birth (10 trials, 14,751 women: RR 0.81, 95% CI 0.64 to 1.03), or stillbirth or death before discharge from hospital (10 trials 15,141 babies; RR 0.89, 95% CI 0.73 to 1.09).Blood pressure in childhood has been assessed in one study: childhood systolic blood pressure greater than 95th percentile was reduced (514 children: RR 0.59, 95% CI 0.39 to 0.91). AUTHORS' CONCLUSIONS: Calcium supplementation appears to almost halve the risk of pre-eclampsia, and to reduce the rare occurrence of the composite outcome 'death or serious morbidity'. There were no other clear benefits, or harms.

Marine oil, and other prostaglandin precursor, supplementation for pregnancy uncomplicated by pre-eclampsia or intrauterine growth restriction.

BACKGROUND: Population studies have shown that higher intakes of marine foods during pregnancy are associated with longer gestations, higher infant birthweights and a low incidence of pre-eclampsia. It is suggested that the fatty acids of marine foods may be the underlying cause of these associations. OBJECTIVES: To estimate the effects of marine oil, and other prostaglandin precursor, supplementation during pregnancy on the risk of pre-eclampsia, preterm birth, low birthweight and small-for-gestational age. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2005), The Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 2) and MEDLINE (1966 to April 2005). SELECTION CRITERIA: All randomised trials comparing oral marine oil, or other prostaglandin precursor, supplementation during pregnancy with either placebo or no treatment. Trials were excluded if their aim was to treat women with established pre-eclampsia or suspected intrauterine growth restriction. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, data extraction and trial quality. MAIN RESULTS: Six trials, involving 2783 women, are included in this review. Three of these were rated as high quality, including the largest trial with 1477 women. Women allocated a marine oil supplement had a mean gestation that was 2.6 days longer than women allocated to placebo or no treatment (weighted mean difference (WMD), 2.55 days, 95% confidence interval (CI) 1.03 to 4.07 days; 3 trials, 1621 women). This was not reflected in a clear difference between the two groups in the relative risk (RR) of birth before 37 completed weeks, although women allocated marine oil did have a lower risk of giving birth before 34 completed weeks' gestation (RR 0.69, 95% CI 0.49 to 0.99; 2 trials, 860 women). Birthweight was slightly greater in infants born to women in the marine oil group compared with control (WMD 47 g, 95% CI 1 g to 93 g; 3 trials, 2440 women). However, there were no overall differences between the groups in the proportion of low birthweight or small-for-gestational age babies. There was no clear difference in the relative risk of pre-eclampsia between the two groups. AUTHORS' CONCLUSIONS: There is not enough evidence to support the routine use of marine oil, or other prostaglandin precursor, supplements during pregnancy to reduce the risk of pre-eclampsia, preterm birth, low birthweight or small-for-gestational age.

Garlic for preventing pre-eclampsia and its complications.

BACKGROUND: The suggestion that garlic may lower blood pressure, inhibit platelet aggregation, and reduce oxidative stress has led to the hypothesis that it may have a role in preventing pre-eclampsia and its complications. OBJECTIVES: To assess the effects of garlic on prevention of pre-eclampsia and its complications. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 2), and EMBASE (1974 to April 2005). SELECTION CRITERIA: Studies were included if they were randomised trials evaluating the effects of garlic on prevention of pre-eclampsia and its complications. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Data were entered on Review Manager software for analysis, and double checked for accuracy. MAIN RESULTS: One trial (100 women) of uncertain quality compared garlic with placebo. Another study was excluded as 29% of women were lost to follow up. There was no clear difference between the garlic and control groups in the risk of developing gestational hypertension (relative risk (RR) 0.50, 95% confidence interval (CI) 0.25 to 1.00) or pre-eclampsia (RR 0.78, 95% CI 0.31 to 1.93). Women allocated garlic were more likely to report odour than those allocated placebo (RR 8.50, 95% CI 2.07 to 34.88), but there were no significant differences in other reported side-effects. The only other outcomes reported were caesarean section (RR 1.35, 95% CI 0.93 to 1.95), and perinatal mortality. There were no perinatal deaths in the study. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend increased garlic intake for preventing pre-eclampsia and its complications. Although garlic is associated with odour, other more serious side-effects have not been reported. Further large randomised trials evaluating the effects of garlic are needed before any recommendations can be made to guide clinical practice.

Rest during pregnancy for preventing pre-eclampsia and its complications in women with normal blood pressure.

BACKGROUND: Women at risk of pre-eclampsia or gestational hypertension are sometimes advised to rest. Whether this, overall, does more good than harm is unclear. OBJECTIVES: To assess the effects of rest or advice to reduce physical activity during pregnancy for preventing pre-eclampsia and its complications in women with normal blood pressure. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (December 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2005), and EMBASE (2002 to August 2005). SELECTION CRITERIA: Studies were included if they were randomised trials evaluating the effects of rest or advise to reduce physical activity for preventing pre-eclampsia and its complications in women with normal blood pressure. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted data. Data were double checked for accuracy. MAIN RESULTS: Two small trials (106 women) of uncertain quality were included. Both recruited women with a singleton pregnancy at moderate risk of pre-eclampsia from 28 to 32 weeks' gestation. There was a statistically significant reduction in the relative risk of pre-eclampsia with four to six hours rest per day (one trial, 32 women; relative risk (RR) 0.05, 95% confidence interval (CI) 0.00 to 0.83), but not of gestational hypertension (RR 0.25, 95% CI 0.03 to 2.00), compared to normal activity. Rest of 30 minutes per day plus nutritional supplementation was associated with a reduction in the risk of pre-eclampsia (one trial, 74 women; RR 0.13, 95% CI 0.03 to 0.51) and also of gestational hypertension (RR 0.15, 95% CI 0.04 to 0.63). The effect on caesarean section was unclear (RR 0.82, 95% CI 0.48 to 1.41). No other outcomes were reported. AUTHORS' CONCLUSIONS: Daily rest, with or without nutrient supplementation, may reduce the risk of pre-eclampsia for women with normal blood pressure, although the reported effect may reflect bias and/or random error rather than a true effect. There is no information about outcomes such as perinatal mortality and morbidity, maternal morbidity, women's views, adverse effects, and costs. Current evidence is insufficient to support recommending rest or reduced activity to women for preventing pre-eclampsia and its complications. Whether women rest during pregnancy should therefore be a matter of personal choice.

Calcium supplementation to prevent pre-eclampsia--a systematic review.

BACKGROUND: Calcium supplementation during pregnancy may prevent high blood pressure and preterm labour. OBJECTIVE: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child adverse outcomes. DESIGN: A systematic review of randomised trials that compared supplementation with at least 1 g calcium daily during pregnancy with placebo. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register (October 2001) and the Cochrane Controlled Trials Register (Issue 3, 2001) were searched and study authors were contacted. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. Data were extracted and analysed. MAIN RESULTS: There was a modest reduction in the risk of pre-eclampsia with calcium supplementation (relative risk (RR) 0.68, 95% confidence interval (CI): 0.57-0.81). The effect was greatest for women at high risk of hypertension (RR 0.21, 95% CI: 0.11-0.39) and those with low baseline calcium intake (RR 0.32, 95% CI: 0.21-0.49). There was no overall effect on the risk of preterm delivery, although there was a reduction in risk among women at high risk of hypertension (RR 0.42, 95% CI: 0.23-0.78). There was no evidence of any effect of calcium supplementation on stillbirth or death before discharge from hospital. There were fewer babies with birthweight < 2,500 g (RR 0.83, 95% CI: 0.71-0.98). In one study, childhood systolic blood pressure > 95th percentile was reduced (RR 0.59, 95% CI: 0.39-0.91). CONCLUSIONS: Calcium supplementation appears to be beneficial for women at high risk of gestational hypertension and in communities with low dietary calcium intake. These benefits were confined to several rather small trials, and were not found in the largest trial to date, conducted in a low-risk population. Further research is required.

Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

BACKGROUND: Calcium supplementation may prevent high blood pressure through a number of mechanisms and may help to prevent preterm labour. OBJECTIVES: The objective of this review was to assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child adverse outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (October 2001) and the Cochrane Controlled Trials Register (Issue 3, 2001) and we contacted study authors. SELECTION CRITERIA: Randomised trials comparing at least one gram daily of calcium during pregnancy with placebo. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. Data extraction was carried out and double entered. MAIN RESULTS: Eleven studies were included, all of good quality. There was a modest reduction in high blood pressure with calcium supplementation (relative risk 0.81, 95% confidence interval 0.74 to 0.89). The effect was greatest for women at high risk of hypertension (relative risk 0.45, 95% confidence interval 0.31 to 0.66) and those with low baseline dietary calcium (relative risk 0.49, 95% confidence interval 0.38 to 0.62). There was also a modest reduction in the risk of pre-eclampsia with calcium supplementation (relative risk 0.68, 95% confidence interval 0.57 to 0.81). The effect was greatest for women at high risk of hypertension (relative risk 0.21, 95% confidence interval 0.11 to 0.39) and those with low baseline calcium intake (relative risk 0.32, 95% confidence interval 0.21 to 0.49). There was no overall effect on the risk of preterm delivery, although there was a reduction in risk amongst women at high risk of hypertension (relative risk 0.42, 95% confidence interval 0.23 to 0.78). There was no evidence of any effect of calcium supplementation on stillbirth or death before discharge from hospital. There were fewer babies with birthweight < 2500g (RR 0.83, 95% CI 0.71-0.98). In one study, childhood systolic blood pressure > 95th percentile was reduced (RR 0.59, 95% CI 0.39-0.91). REVIEWER'S CONCLUSIONS: Calcium supplementation appears to be beneficial for women at high risk of gestational hypertension and in communities with low dietary calcium intake. Optimum dosage requires further investigation.

Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

BACKGROUND: Calcium supplementation may prevent high blood pressure through a number of mechanisms and may help to prevent preterm labour. OBJECTIVES: The objective of this review was to assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child adverse outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register and we contacted study authors. Date of last search: February 2000. SELECTION CRITERIA: Randomised trials comparing at least one gram daily of calcium during pregnancy with placebo. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. Data extraction was carried out and double entered. MAIN RESULTS: Ten studies were included, all of good quality. There was a modest reduction in high blood pressure with calcium supplementation (relative risk 0.81, 95% confidence interval 0.74 to 0.89). The effect was greatest for women at high risk of hypertension (relative risk 0.35, 95% confidence interval 0.21 to 0.57) and those with low baseline dietary calcium (relative risk 0.49, 95% confidence interval 0.38 to 0.62). There was also a modest reduction in the risk of pre-eclampsia with calcium supplementation (relative risk 0. 70, 95% confidence interval 0.58 to 0.83). The effect was greatest for women at high risk of hypertension (relative risk 0.22, 95% confidence interval 0.11 to 0.43) and those with low baseline calcium intake (relative risk 0.32, 95% confidence interval 0.21 to 0.49). There was no overall effect on the risk of preterm delivery, although there was a reduction in risk amongst women at high risk of hypertension (relative risk 0.43, 95% confidence interval 0.24 to 0. 79). There was no evidence of any effect of calcium supplementation on stillbirth or death before discharge from hospital. There were fewer babies with birthweight, <2500g (RR 0.83, 95% CI 0.71-0.98). In one study, childhood systolic blood pressure >95th percentile was reduced (RR0.59, 95% CI 0.39-0.91). REVIEWER'S CONCLUSIONS: Calcium supplementation appears to be beneficial for women at high risk of gestational hypertension and in communities with low dietary calcium intake. Optimum dosage requires further investigation.

Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

BACKGROUND: Calcium supplementation may prevent high blood pressure through a number of mechanisms and may help to prevent preterm labour. OBJECTIVES: The objective of this review was to assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child adverse outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register and we contacted study authors. SELECTION CRITERIA: Randomised trials comparing at least one gram daily of calcium during pregnancy compared to placebo. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. Data extraction was carried out independently by two reviewers. MAIN RESULTS: Nine studies were included, all of good quality. There was a modest reduction in high blood pressure with calcium supplementation (relative risk 0.80, 95% confidence interval 0.73 to 0.88). The effect was greatest for women at high risk of hypertension (relative risk 0.35, 95% confidence interval 0.21 to 0.57) and those with low baseline dietary calcium (relative risk 0.49, 95% confidence interval 0.38 to 0.62). There was also a modest reduction in the risk of pre-eclampsia with calcium supplementation (relative risk 0. 72, 95% confidence interval 0.60 to 0.86). The effect was greatest for women at high risk of hypertension (relative risk 0.22, 95% confidence interval 0.11 to 0.43) and those with low baseline calcium intake (relative risk 0.32, 95% confidence interval 0.21 to 0.49). There was no overall effect on the risk of preterm delivery, although there was a reduction in risk amongst women at high risk of hypertension (relative risk 0.42, 95% confidence interval 0.23 to 0. 78). There was no evidence of any effect of calcium supplementation on stillbirth or death before discharge from hospital. REVIEWER'S CONCLUSIONS: Calcium supplementation appears to be beneficial for women at high risk of gestational hypertension and in communities with low dietary calcium intake. Optimum dosage requires further investigation.