Postpartum hemorrhage (blood loss > 500 ml after a vaginal delivery and > 1,000 ml after a c-section) complicates 2.9% of deliveries in the United States. It is a leading cause of both maternal complications, such a blood transfusions and hysterectomy, and maternal death. The rate of postpartum hemorrhage has been slowly increasing, so anything we can do to further our understanding and hopefully reduce the risk is needed.
There is a concern that specific antidepressants, those that affect levels of serotonin, may affect the risk of bleeding. Serotonin is important for platelet function and working platelets are needed for blood to clot. Serotonin may also affect how well the uterus contracts, an important mechanism to stop bleeding after delivery. A couple of studies suggest an association between antidepressants and postpartum hemorrhage although these studies have some significant limitations.
A new study in BMJ provides more information. The researchers analyzed records of over 100,000 women receiving maternal care and covered by Medicaid. They attempted to drill down on exposure to antidepressants by cross referencing with the dispensing date of the medication. The investigators also looked at additional factors that can affect bleeding after delivery, such as age, multiple pregnancy or not, method of delivery, diabetes, and certain medications.
The investigators factored in obesity, but the specific data set did not have accurate BMI data so they collected obesity data from a NHANES data set that addressed depression and obesity and applied the information to their cohort. To my knowledge BMI at delivery is not part of the NHANES data (none of the briefs I looked at had that specific data), so I just don’t see how obesity rates in non-pregnant depressed women can be reliably extrapolated to obesity at delivery date. However, I readily admit this type of sensitivity analysis is far beyond my ability to understand. Controlling for obesity is essential as one study reports an almost doubling of the risk of post partum hemorrhage among obese women and in another study the rate of postpartum hemorrhage was 5.2% among women with a BMI over 40 who had a normal vaginal delivery.
The other big issue with the BMJ study is there is no data on smoking or nutritional status.
What did the study show?
The absolute risk of post partum hemorrhage was…
- 2.4% for women without mood/anxiety disorders and not taking antidepressants
- 2.8% for women with mood/anxiety disorders and not taking antidepressants
- 4.0% for women taking an SSRI* at delivery and 3.8% for women taking a SNRI* at delivery
The increased risk of postpartum hemorrhage with antidepressants was 1.4-1.5 fold, although when obesity was adjusted for the risk was 1.3-1.4 fold.
So what does this mean?
- The risk of postpartum hemorrhage appears to be increased with antidepressants. The maximum risk translates into one addition post partum hemorrhage for every 80 to a 100 women taking an antidepressant.
- Given the way obesity was addressed, the role obesity plays in post partum hemorrhage, the complex interplay between depression and obesity, and the lack of data on smoking and nutrition the absolute increased risk of postpartum hemorrhage directly attributable to the drugs themselves is still really unknown.
- Every person has a unique risk benefit ratio. This data may have different implications for a woman with multiple risk factors for post partum hemorrhage who needed 3 units of blood after her last delivery and barely escaped with her uterus intact compared with a woman with no risk factors for bleeding and a previous uncomplicated delivery.
- This study is not robust enough in my opinion to do anything but raise awareness, especially considering untreated depression can be disastrous and stopping antidepressants around the time of delivery, a particularly vulnerable time, make be especially risky.
What’s the take home?
Postpartum hemorrhage remains a concern and knowing all the risk factors, which appear to also include antidepressants, helps to be prepared.
* SSRI = selective serotonin reuptake inhibitor, SNRI = serotonin-norepinephrine reuptake inhibitor