Acute Heart Failure in Pregnancy and Postpartum: Role of Iron Deficiency and Anemia in an Indian Multicenter Case–Control Study

ABSTRACT Background Cardiovascular diseases in pregnant and postpartum women remain under-researched, despite being the leading cause of indirect maternal deaths. In low- and middle-income countries (LMICs), anemia and iron deficiency are highly prevalent and may compound the cardiovascular stress of pregnancy, yet their contribution to maternal acute heart failure (AHF) is poorly understood. This study investigated the association between AHF in pregnancy/ postpartum and iron deficiency and anemia and assessed whether they remain consistent for peripartum cardiomyopathy (PPCM). Methods We conducted a multicenter case–control study in ten hospitals across four Indian states (February 2019–November 2024). Cases were pregnant/postpartum women with echocardiography-confirmed AHF as per standard definition; controls were postpartum women within 48 hours of childbirth without history/symptoms of heart disease recruited on the day of each case presentation. Blood samples collected at recruitment were analyzed for hemoglobin, ferritin, transferrin saturation (TSAT), soluble transferrin receptor (sTfR), and hepcidin. Multivariable logistic regression models assessed associations between iron status, anemia, and AHF, adjusting for potential confounders. Subgroup analyses were performed for PPCM. Findings Among 532 women with suspected heart failure, 317 had echocardiography-confirmed AHF and were compared with 1,091 controls. Moderate (Hb 7–9.9 g/dL) and severe (Hb <7 g/dL) anemia were respectively associated with 1.6-times (adjusted odds ratio [aOR] 1.59; 95% CI 1.10–2.32) and 6.1-times (aOR 6.09; 95% CI 3.35–11.07) the odds of AHF in women without anemia. Iron deficiency based on increasing levels of sTfR (aOR 1.47, 95% CI 1.32–1.63), lowest two hepcidin quintiles (aOR 4.07, 95% CI 2.26–7.32; aOR 2.06 95% CI 1.14–3.73) and low TSAT (aOR 1.50, 95% CI 1.01–2.21) were independently associated with AHF. Associations persisted after adjusting for hypertensive disorders of pregnancy and excluding women with pre-existing cardiac problems, and were consistent in the PPCM subgroup. Interpretation Iron deficiency and moderate-to-severe anemia substantially increase the risk of AHF in pregnancy and postpartum, independent of hypertensive or pre-existing conditions. These findings identify iron deficiency as a major, preventable, and under-recognized contributor to maternal cardiac complications in LMICs, highlighting the need for targeted antenatal screening and correction. CLINICAL PERSPECTIVE What is new? This is the first multicenter study to demonstrate a strong, independent association between iron deficiency and acute heart failure during pregnancy and postpartum. The findings disentangle the effects of anemia and iron deficiency and confirm consistency across the PPCM subgroup. The findings identify iron deficiency with and without anemia as an important female-specific risk factor for pregnancy-associated acute heart failure. What are the clinical implications? Iron deficiency and anemia represent modifiable risk factors for maternal heart failure. Routine screening and timely correction of iron deficiency in pregnancy could reduce the risk of acute heart failure and related maternal deaths in LMICs. Integration of cardiac and iron parameter assessments should be prioritized in antenatal and postpartum care programs.