Effect of prophylactic intravenous calcium gluconate compared to placebo on postpartum blood loss in women with hypertensive disorders of pregnancy at term gestation undergoing emergency caesarean delivery: A randomised, double-blinded, placebo-controlled.

Post-partum hemorrhage (PPH) is the leading preventable cause of maternal mortality and morbidity. WHO in its Postpartum Haemorrhage Summit – 2023 declared that each year about 14 million women experience PPH resulting in about 70,000 maternal deaths globally. Even in cases where women survive, there is frequently a requirement for immediate surgical interventions to manage the bleeding, potentially resulting in long-term reproductive challenges1. Hypertensive Disorders of Pregnancy (HDP) is another spectrum of disorders resulting in significant maternal mortality and morbidity, complicating 5% to 10% of all pregnancies. Women with HDP are reported to have an increased risk of postpartum haemorrhage2. In that spectrum, women with pre-eclampsia are more prone to postpartum hemorrhage, with an increased risk of 1.53 times relative to other disorders.3 Though uterine atonicity, trauma (lacerations or uterine rupture), retained placenta or clots, and clotting-factor deficiency are found to be the significant causes for postpartum haemorrhage, uterine atonicity tops the list, accounting for approximately 70% of cases.4 The prophylactic administration of uterotonic agents as part of active management of the third stage of labour has been proven to reduce rates of PPH. Despite the availability of interventions, the rate of PPH is still relatively high, which poses a significant risk to women who may experience heavy bleeding postpartum, which may even lead to death.5

Rationale: Understanding the role of coagulation in postpartum haemostasis and uterine contraction is crucial. Ionised calcium plays an essential role as a coagulation cofactor. Recent studies have shown that low calcium levels are independently associated with postpartum blood loss6. Preeclampsia typically presents with haemorrhagic complications owing to its strong correlation with angiogenic factors.   Calcium is postulated to have a positive inotropic effect on uterine smooth muscle. It functions as an essential co-factor for the activation of factors II and X. Hence, calcium gluconate, a readily available safer intravenous form of calcium salt, can be used as a prophylactic measure to reduce blood loss in the third stage of labour7.