Episode #79 Anemia, Iron Supplements, and Maternal Patient Safety

January 4, 2022

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Welcome to the next installment of the Anesthesia Patient Safety podcast hosted by Alli Bechtel.  This podcast will be an exciting journey towards improved anesthesia patient safety.

The focus for our maternal patient safety themed show is Iron Deficient Anemia in Pregnancy. Our featured article today is “Iron Deficient Anemia During and After Pregnancy: How Can We Make a Difference?” by Jack Peace and Jennifer Banayan. We have exclusive content from Jack Peace on the show today.

Here are the references to the studies that we discussed on the show today.

  1. Woodward T, Kay T, Rucklidge M. Fetal bradycardia following maternal administration of low-molecular-weight intravenous iron. Int J Obstet Anesth. 2015;24:196–197.
  2. Froessler B, Gajic T, Dekker G, Hodyl NA. Treatment of iron deficiency and iron deficiency anemia with intravenous ferric carboxymaltose in pregnancy. Arch Gynecol Obstet. 2018 Jul;298(1):75-82.

Treatment options for iron deficiency anemia during pregnancy include the following:

  1. Oral iron supplements: safe, inexpensive, available over the counter, and simple to store
  2. Intravenous iron supplementation: For patients who are unable to tolerate side effects from oral iron supplements, with insufficient response from oral iron supplements, who need a rapid correction, and with malabsorptive disorders.

Potential role for the Perioperative Surgical Home: Reflex iron testing early in pregnancy to help diagnose and treat iron deficiency anemia with anemia clinics with established protocols for the IV Iron infusions and appropriate maternal and fetal monitoring.

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© 2022, The Anesthesia Patient Safety Foundation

Hello and welcome back to the Anesthesia Patient Safety Podcast.  My name is Alli Bechtel, and I am your host. Thank you for joining us for another show. Last week, we discussed nitrous oxide use on labor and delivery units including the safety and efficacy of this treatment option to close out the 2021 year! Well, it’s 2022 and we are once again returning to the theme of maternal patient safety with another great show for you today!

Before we dive into the episode today, we’d like to recognize Blink Device Company, a major corporate supporter of APSF. Blink Device Company has generously provided unrestricted support to further our vision that “no one shall be harmed by anesthesia care”. Thank you, Blink Device Company – we wouldn’t be able to do all that we do without you!”

The focus for our maternal patient safety themed show is Iron Deficient Anemia in Pregnancy. To follow along with us, head over to APSF.org and click on the current Newsletter. That’s right, there is still more great content from the October 2021 Newsletter. Then, scroll down until you get to our featured article today which is “Iron Deficient Anemia During and After Pregnancy: How Can We Make a Difference?” by Jack Peace and Jennifer Banayan. I will include a link in the show notes as well. We wanted to start the New Year off right, so we have exclusive content from one of the authors of the article here on the show today. Here he is now:

[JP] “Hi, my name is Jack Peace, and I am an obstetric anesthesiologist at the Temple University in Philadelphia, PA. I am an assistant professor at the Temple University Lewis Katz School of Medicine.”

[Bechtel] Now, to kick off the show, I asked Peace, why do you feel so passionate about this topic. Let’s take a listen to what he had to say.

[JP] “We’ve known for years that iron deficiency anemia has negative impacts for both mother and baby. As obstetric anesthesiologists, we often find ourselves on the front lines when peripartum hemorrhage occurs. It makes sense that women with anemia are far more likely to require blood transfusion or to die if transfusion is not available. As anesthesiology as a specialty moves towards caring for patients outside of the operating room as a part of the peripartum home, I felt that this was a great area for our specialty to help intervene before peripartum hemorrhage occurs. I hope that by studying outcomes and leveraging the tools of the perioperative home, we can help improve maternal patient outcomes both in US and around the world.”

[Bechtel] As we have discussed on past shows, rates for severe maternal morbidity have been increasing in the United States, so this topic is timely, and this is an area where anesthesia professionals can make a difference and help to improve maternal patient safety. With that, let’s get into the article.

Let’s start with some background about the scope of the problem, anemia in pregnant patients. Did you know that anemia affects almost one in three pregnant patients worldwide? This is a common condition and antepartum anemia is associated with several adverse outcomes such as preterm labor, miscarriage, growth restriction, cesarean delivery, and intrauterine infection. When anemia carries over into the postpartum period, it has been associated with adverse maternal outcomes including depression, fatigue, and impaired cognition. This article is all about iron deficiency anemia in part because it is the most common cause of peripartum maternal anemia and because there are treatments available including oral and intravenous iron replacement therapy that improve hemoglobin and hematocrit levels. Unfortunately, what the literature does not tell us is whether this treatment has an impact on maternal and fetal outcomes. The authors ask 2 important questions:

  • How can we make a meaningful difference in the treatment and management of maternal anemia so as to improve clinical outcomes?
  • And how can we as anesthesia professionals partner with our obstetric colleagues to decrease the impact of anemia on childbirth?

Peace mentioned the perioperative home earlier in the show, so let’s take a closer look at how this can be used to address this problem. As part of the perioperative home, anesthesia professionals already have society-level guidelines for the treatment of anemia, but these guidelines may not be applicable to pregnant patients in general. In addition, anesthesia professionals are consulted often for pregnant patients with certain hematologic conditions including thrombocytopenia or heritable coagulopathies, but it is rare that anemic pregnant patients are seen by an anesthesia professional prior to arriving on the labor and delivery unit and by this time, it may be too late for iron replacement therapy. This is an excellent opportunity for anesthesia professionals to partner with obstetricians and hematologists to address maternal iron deficiency anemia from diagnosis to appropriate management.

It’s time to do a further review of iron deficiency anemia so that we can further address the treatment and next steps. Iron deficiency anemia may be seen at different time during pregnancy and in different populations depending on pre-existing nutritional deficiencies and iron homeostasis during pregnancy. Almost 50% of pregnant patients in low- and middle-income countries develop iron deficiency anemia. In developed countries, there are significant racial disparities. In the 2012 study by Mohamed and colleagues, African American women developed iron deficiency anemia at three times of the rate than non-Hispanic white women. This is a big threat to patient safety since iron deficiency anemia is associated with the following: increases in hemorrhagic shock, cardiovascular failure, peripartum transfusion, and increased rates of infection. This is also a patient safety threat for our smallest patients as well since maternal anemia is associated with neurodevelopmental disorders in children. This data comes from a large cohort study published in 2019 with over half a million children.

We have identified that there is a problem, iron deficiency anemia, as well as maternal and fetal risks associated with this condition. The good news is that there is something that we can do about it. So, freshen up you cup of coffee or tea and let’s discuss the treatment of iron deficiency anemia. The first line therapy includes oral iron supplements which are safe and inexpensive, available over the counter and simple to store. Unfortunately, compliance with oral iron supplements is limited by very common GI side effects including nausea, dyspepsia, or constipation. We have evidence that oral iron supplements can yield modest improvements in maternal hemoglobin and ferritin levels. What about further downstream effects? The studies did not show consistent improvement in decreased transfusion requirements, improved recovery, or higher birthweight. That the studies did not show consistent improvements in outcomes is not surprising for the following reasons:

  • Delayed diagnosis of iron-deficiency anemia since earlier diagnosis and intervention is more likely to have an impact on maternal and neonatal outcomes
  • And many of these are smaller studies without consistent methodology

There is a call to action for large-scale studies with consistent treatment protocols to evaluate the impact of early treatment for maternal iron deficiency anemia on maternal and fetal outcomes.

Another treatment option is intravenous iron supplementation, and this may be a good option for patients who are unable to tolerate the side effects from oral iron supplements. This therapy may also be effective for patients with insufficient response from oral iron supplements, who need a rapid correction, and with malabsorptive disorders. Historically, there was a concern for anaphylaxis associated with older intravenous iron formulations. Currently, there are newer, lower molecular weight iron dextran and non-dextran iron formulations available with a lower risk for anaphylaxis and are considered safe to administer during pregnancy. Some of the side effects from intravenous iron administration include skin staining and transient bronchospasm, but in general this therapy is well tolerated. The downside is that this treatment requires a clinic visit and is more expensive than oral iron supplements. Keep in mind that studies have shown that this is safe for treatment of iron deficiency anemia during pregnancy, but there is still a need to develop protocols and set guidelines for appropriate maternal as well as fetal heart rate monitoring during the infusion. A 2015 case report Woodward and colleagues describes a case of severe fetal bradycardia during IV infusion of a low molecular weight iron supplement that ultimately required an emergent cesarean section. The 2018 study by Froessler evaluated over 800 pregnant patients who were treated with IV iron supplementation during pregnancy and reported no changes in fetal heart rate pattern related to the therapy. The authors of this study concluded that ferric carboxymaltose infusion is safe and effective for the treatment of iron deficiency anemia during pregnancy. I will include the citations to these papers in the show notes as well.

Now, is the time we have all been waiting for…what can anesthesia professionals do to help improve maternal and fetal patient safety when it comes to iron deficiency anemia? Let’s start at the pre-anesthesia clinic. This may be an appropriate space for reflex iron testing early in pregnancy to help diagnosis and perhaps even treat iron deficiency anemia. Then, obstetricians could refer patients who require IV iron infusions to perioperative anemia clinics which have established protocols for the infusions and appropriate monitoring. We have seen that in cardiac surgery patients who undergo short term treatment for anemia prior to cardiac surgery, there is a decrease in perioperative transfusions, and this may be something that we can accomplish in pregnant patients as well, short term treatment of anemia with reduced peripartum transfusions. In places with perioperative iron clinics, there is a need for clinical research to continue to evaluate the safety and efficacy of this therapy.

The authors round out the discussion with a review of recommendations for blood transfusions in the setting of peripartum hemorrhage. The decision to transfuse requires collaboration between anesthesia professionals and obstetricians. The most recent recommendations from the ASA and the American Association of Blood Banks includes transfusion threshold of hemoglobin of 7 rather than 10 given the increased harm associated with a liberal transfusion strategy and the use of cell salvage and antifibrinolytic therapy may help to decrease the risk for blood transfusion. For postpartum hemorrhage, decisions must be made quickly, and the full clinical picture must be evaluated to help keep patients safe.

Let’s put it all together into a quality improvement toolkit focused on iron deficiency anemia and look at what was implemented at St. Michael’s Hospital in Toronto, Canada. Check out figure 1 in the article. This toolkit includes pathways for diagnosis with reflex iron studies to help with earlier diagnosis and pregnancy-specific threshold, treatment with early referral for IV iron therapy if oral supplementation is not tolerated or insufficient with help from their pre-existing pre-anesthesia clinic, and outcomes research that includes identifying clinically significant maternal and neonatal outcomes as well as consistent treatment protocols and outcomes measures to study this on a larger scale. At this institution, the implementation of the protocol was successful with increased ferritin testing and decreased number of transfusions by 50%. The same success has been seen at other institutions with similar programs – decreased anemia and decreased transfusions.

There is one more topic that we need to address, postpartum anemia which is associated with maternal adverse effects including fatigue, depression, and impaired cognition and is more likely to occur in patients with antepartum iron deficiency anemia and postpartum hemorrhage. Treatment for postpartum anemia may include oral iron supplementation, but intravenous iron therapy appears to be a better first line option since it works fast with a more significant rise in hemoglobin. This may be a good option for patients who are asymptomatic and hemodynamically stable in order to decrease blood transfusions. A 2014 study revealed only slightly decrease in fatigue in patients who received blood transfusion for postpartum anemia compared to those that did not. Once again, we need further studies looking at blood transfusions compared to IV iron treatment to determine the most appropriate treatment for postpartum anemia and to help keep patients safe.

The authors conclude with a call to action that I am going to read now:

“Awareness of the safety issues surrounding the consequences and treatment of peripartum IDA is paramount for anesthesia professionals responsible for the care of these patients.”

Before we wrap up for today, we are going to hear from Peace again. He shares with us the following:

[JP] “We have a number of proven and safe treatments for peripartum anemia which include both oral and intravenous iron supplementation, but studying this problem is hard and knowing when in pregnancy to treat patients and how to measure outcomes is an open question. For instance, many of the studies that have looked at these treatments for maternal anemia have generally focused on process outcomes like maternal hemoglobin and haven’t been designed to detect clinically meaningful outcomes like the rate of maternal transfusion or long-term fetal outcomes. While initial results have shown some promise, I hope that as we move forward, we can identify treatments and timing that most directly improve patient outcomes.”

[Bechtel] Thank you so much to Peace for contributing to the show today. This is the time for teamwork between anesthesia professionals, obstetricians, and hematologists to come together perhaps in a peri-anesthesia clinic setting to work towards earlier diagnosis, effective treatment, appropriate blood conservation strategies and studying clinical outcomes to keep patients with maternal iron deficiency anemia safe.

If you have any questions or comments from today’s show, please email us at [email protected] Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. We hope that you will visit APSF.org for detailed information and check out the show notes for links to all the topics we discussed today.

Happy 2022! If you made a new year’s resolution to listen to the Anesthesia Patient Safety Podcast, congratulations on completing this task! Now, we hope that you will subscribe to our show, give us a 5-star rating and continue to listen all year long. We hope that you will share this show with your friends and colleagues, and anyone interested in the latest news and updates in perioperative and anesthesia patient safety.

Until next time, stay vigilant so that no one shall be harmed by anesthesia care.

© 2022, The Anesthesia Patient Safety Foundation