Authors' Response: Postpartum bleeding is reduced with sublingual powdered misoprostol when compared with oxytocin injection, but a new formulation of misoprostol is unlikely to revolutionise postpartum haemorrhage care

Mrutyunjaya B. Bellad, Professor, Department. of Obstetrics. & Gynaecology,

Other Contributors:

February 17, 2013

Dear Editor,

We thank Beverly Winikoff and Jill Durocher for their thoughtful commentary.(1) Winikoff and Durocher note that the incidence of PPH in our study's (2) oxytocin group was higher than expected. This deviance can occur, particularly in studies with relatively small samples such as ours. Regardless, the randomization produced study groups with similar characteristics to each other,(2) although this particular sample of women had higher risk of postpartum hemorrhage than the general population, something that might be expected in the study hospital, a referral center.

Our results were also consistent with a previously published study comparing sublingual administration of 400 mg tablet misoprostol with oxytocin, one among various criteria upon which causal associations are judged to exist that our study met.(3) We agree and question the pragmatism of a powdered formulation in the article.(2) The potential to reduce drug costs by 33% remains substantial for a medication that is widely recommended for PPH prevention.(4)

We think there is little basis to question the drug potency in our study. The drug manufacturer, Astra-Zeneca provided us with the study medication directly, and we assume the potency was acceptable to the manufacturer upon distribution. Unlike the oxytocin stored under variable field conditions, potentially exposed to sunlight and high temperatures (potentially without refrigeration prior to their purchase in the cited Ghana study),(5) the packaged study medications were stored in a refrigerator maintained at 2 to 8 degrees Celsius within the clinical pharmacy department at our hospital until their use as stated in the manuscript.(2) What is not well known is whether intramuscular administration of oxytocin is less efficacious than oxytocin administered in intravenous solution; the Cochrane Review of uterotonics for PPH prevention typically analyzed IM and IV administration jointly(6) and whether the strong observed effect is attributable to the powdered formulation.

We agree that further investigation of these issues will clarify the questions our article raises about sublingual administration of lower dose misoprostol for PPH prevention.

References

1. Winikoff B, Durocher J. Postpartum bleeding is reduced with sublingual powdered misoprostol when compared with oxytocin injection, but a new formulation of misoprostol is unlikely to revolutionise postpartum haemorrhage care. Evid Based Med. 2012 Nov 2. 10.1136/eb-2012-100966.

2. Bellad M, Tara D, Ganachari M, et al. Prevention of postpartum haemorrhage with sublingual misoprostol or oxytocin: a double-blind randomised controlled trial. BJOG 2012;119:975-86.

3. Rothman KJ. What is Causation?" in Epidemiology: An Introduction. Oxford University Press, New York. 2012;pp 33

4. WHO recommendations for the prevention and treatment of postpartum haemorrhage 2012 http://apps.who.int/iris/bitstream/10665/75411/1/9789241548502_eng.pdf

5. Stanton C, Koski A, Cofie P, et al. Uterotonic drug quality: an assessment of the potency of injectable uterotonic drugs purchased by simulated clients in three districts in Ghana. BMJ Open 2012;2:e000431.

6. Gülmezoglu AM, Forna F, Villar J, Hofmeyr GJ. Prostaglandins for preventing postpartum haemorrhage. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD000494. DOI: 10.1002/14651858.CD000494.pub3.

Conflict of Interest:

None declared

Conflict of Interest

None declared