Studies suggest a potential direct and dose-response relationship between anemia and postpartum hemorrhage

Anemia is a concern in pregnancy and is usually addressed with iron supplementation. Its linkage to postpartum hemorrhage has been of concern because those who are anemic are likely to expire more rapidly once blood loss occurs.

Dating back to the early 2000s the evidence was firmly mixed. While suspicion of a connection was evident, it was clear that there were many questions and unknowns. In an article published in 2000 by The American Journal of Clinical Nutrition, discussing current knowledge on anemia and pregnancy, it was argued that a link between anemia and subsequent maternal mortality could not be proven because they could both be caused by another factor, like PPH. In other words, it was unclear whether anemia or PPH came first. 

Moreover, the focus on the relationship between anemia and maternal mortality rather than anemia and PPH in these early studies highlights another intertwining factor in the relationship between anemia, PPH, and maternal mortality - the specific role of anemia. Did anemia increase the risk of PPH or did it only increase the risk of mortality from PPH? This was a question implicitly asked throughout studies in the early 2000s. It was suspected that anemia made a woman less able to withstand the blood loss associated with childbirth, even at levels below PPH. As the World Health Organization quotes in a 2004 document on the subject of anemia and childbirth, “Even a blood loss of 100 ml can cause circulatory shock and death.” This idea was supported by studies that showed no difference in risk of PPH across anemic and nonanemic pregnant women, but found a statistically significant increase in the use of blood transfusions in the anemic group. 

Studies from 2008 and onwards are beginning to show that anemia may have a direct effect on the risk of PPH. In a study published in the Journal of Health, Population and Nutrition in 2008, a strong association was found between moderate-to-severe anemia at 28 weeks gestation and a higher severity of blood loss at delivery and postpartum, after adjusting for confounding factors like labor and delivery variables and socioeconomic status that made evidence “inconclusive” in the early 2000s. The investigators attributed this association to the following:

Decreased uterine blood flow or low uterine muscle strength may contribute to inefficient uterine contractions and contribute to blood loss, potentially mediated by low body iron stores (serum ferritin <100 μg/L) and, therefore, iron-deficiency anaemia. Our data are consistent with this latter hypothesis.

Another study published in the Journal of Surgery Pakistan in 2008, found a similar association, calling it causal. They postulated that the biological mechanism for this causal relationship involved the impaired transport of hemoglobin and oxygen to the uterus and tissue enzyme and cellular dysfunction. These are both caused by iron-deficiency anemia and lead to impaired myometrial contractility and atonic uterus, the main cause of PPH. 

In addition, there is increasing evidence showing that the risk of PPH increases with the degree of anemia. A study published in 2012 in the International Journal of Gynecology & Obstetrics looked at the role of nitric oxide (NO) in increasing the risk of PPH. Nitric oxide is a molecule that causes relaxation and vasodilation of muscle and increases 7.5-fold with moderate-to-severe iron-deficiency anemia. They found that women with mild anemia - which does not cause a rise in NO - did not have an increased risk of PPH, but for women with moderate-to-severe anemia, which does cause a rise in NO, their risk for PPH did increase (after adjusting for confounders). Another study found that women with PPH who had to undergo a hysterectomy to save their life were significantly more likely to have severe anemia and higher blood loss compared to women with PPH who did not need to undergo a hysterectomy. A systematic review, published in the Annals of the New York Academy of Sciences last year, showed a dose-response relationship between severity of anemia and PPH incidence. These studies are pointing to a potential direct and dose-response relationship between anemia and PPH.

By Mikaela Carrillo

References

(1) Anemia and iron deficiency: effects on pregnancy outcome, The American Journal of Clinical Nutrition, May 2000

(2) Effects of Iron Supplementation on Maternal Hematologic Status in Pregnancy, American Journal of Public Health, February 2002

(3) Preventing postpartum hemorrhage in low-resource settings, International Journal of Gynecology & Obstetrics, June 2002

(4) Maternal and perinatal outcome in varying degrees of anemia, International Journal of Gynecology & Obstetrics, November 2002

(5) Comparative Quantification of Health Risks Global and Regional Burden of Disease Attributable to Selected Major Risk Factors, World Health Organization, 2004

(6) Maternal and fetal outcome after severe anemia in pregnancy in rural Ghana, Acta Obstetricia et Gynecologica Scandinavica, January 2006

(7) Association between Anaemia during Pregnancy and Blood Loss at and after Delivery among Women with Vaginal Births in Pemba Island, Zanzibar, Tanzania, Journal of Health, Population and Nutrition, June 2008 

(8) Severe anemia and adverse pregnancy outcome, Journal of Surgery Pakistan, October - December 2008

(9) Raised nitric oxide levels may cause atonic postpartum hemorrhage in women with anemia during pregnancy, International Journal of Gynecology & Obstetrics, February 2012

(10) Postpartum hemorrhage is related to the hemoglobin levels at labor: Observational study, Alexandria Journal of Medicine, 2015

(11) Effects of hemoglobin levels during pregnancy on adverse maternal and infant outcomes: a systematic review and meta‐analysis, Annals of the New York Academy of Sciences, May 2019

Photo Credit

UN Photo/Martine Perret

Timor-Leste

10 February 2010

Photo # 428162