Calcium Supplementation During Pregnancy for Preventing Hypertensive Disorders Is not Associated with Changes in Platelet Count,Urate, and Urinary Protein: a Randomized Control Trial

Objective. To test the hypothesis that calcium supplementation inhibits the underlying pathological processes in women with preeclampsia. Methods. Seven hundred and eight nulliparous women were enrolled in a WHO randomized double-blind trial, who received 1.5 g of calcium or placebo from 20 weeks of pregnancy or earlier. Platelet count, serum urate, and urinary protein/creatinine ratio were measured at or near 35 gestational weeks. Results. No difference was detected in rates of abnormal platelet count (relative risk [RR] 1.18; 95% confidence interval [CI], 0.63 to 2.18), serum urate level (1.0; 0.64 to 1.57) or urine protein/creatinine ratio (1.01; 0.76 to 1.34). This was consistent with the main trial finding of no difference in the incidence of ‘dipstick’ proteinuria between women receiving calcium and those receiving placebo (8312 women; RR, 1.01; 95% CI, 0.88 to 1.15). Conclusions. An effect of calcium supplementation in the second half of pregnancy on the rate of abnormal laboratory measures associated with preeclampsia was not demonstrated.     

Administration of 400 μg of misoprostol to augment routine active management of the third stage of labor

Objective

To assess the effectiveness and safety of the administration of misoprostol, an orally active prostaglandin, in addition to routine uterotonic therapy as part of the active management of the third stage of labor.

Methods

The present study was a hospital-based, decentralized, multi-center, randomized, placebo-controlled, double-blind trial. We enrolled 1103 women (out of a target sample size of 1180) at 4 hospitals in South Africa, Uganda, and Nigeria. Participants received a sublingual dose of 400 μg of misoprostol or a placebo, in addition to standard active management of the third stage of labor, after vaginal birth.

Results

The baseline characteristics of the participants were comparable. The difference in the primary outcome of blood loss of 500 mL or more within 1 hour of randomization was not significant between the 2 groups (misoprostol 22/546 [4.0%] versus placebo 35/553 [6.3%]; relative risk, 0.64; 95% confidence interval, 0.38-1.07). Shivering and pyrexia occurred more frequently in the misoprostol group. No maternal deaths occurred.

Conclusion

The present study did not confirm a beneficial effect of administering 400 μg of misoprostol, in addition to routine uterotonic therapy, during the third stage of labor, but was consistent with other trials showing a cumulative modest benefit. Where routine uterotonics are available for prophylactic use, any potential benefit of misoprostol might not outweigh the likelihood of adverse effects. Trial registered on clinical trials.gov: NCT 00124540.     

Misoprostol for treating postpartum haemorrhage: a randomized controlled trial [ISRCTN72263357]

Background  

Postpartum haemorrhage remains an important cause of maternal death despite treatment with conventional therapy. Uncontrolled studies and one randomised comparison with conventional oxytocics have reported dramatic effects with high-dose misoprostol, usually given rectally, for treatment of postpartum haemorrhage, but this has not been evaluated in a placebo-controlled trial.     

A double-blind, randomized, placebo-controlled trial of misoprostol and routine uterotonics for the prevention of postpartum hemorrhage

Objective

To assess the effects of 400-μg sublingual misoprostol plus routine uterotonics on postpartum hemorrhage.

Methods

A double-blind, placebo-controlled, randomized study was performed. After delivery of the child, eligible women received routine uterotonics and were randomly allocated to receive 400-μg misoprostol or placebo sublingually. The primary outcome measure was blood loss of at least 500 mL within 1 hour of taking the trial tablets.

Results

In total, 672 women received misoprostol and 673 received placebo. The baseline data were similar for both groups. Misoprostol plus routine uterotonics reduced postpartum blood loss, but the effect was not significant for blood loss of at least 500 mL (relative risk [RR] 0.96; 95% confidence interval [CI], 0.63-1.45) or blood loss of at least 1000 mL (RR 0.50; 95% CI, 0.15-1.66). Misoprostol also reduced the need for non-routine oxytocin, manual removal of the placenta, and hysterectomy, but these differences were not significant either. Misoprostol was associated with pyrexia and moderate/severe shivering. There was no death in either group.

Conclusion

Misoprostol plus routine uterotonics resulted in modest reductions of blood loss in the third stage of labor, but the effects did not reach statistical significance. Larger studies are recommended.