An epidemiological investigation of iron deficiency in indian women diagnosed with peripartum cardiomyopathy

Background: Peripartum cardiomyopathy (PPCM) is a serious cardiac complication affecting pregnant and postpartum women. The primary mechanism described for PPCM relates to prolactin signalling, but the determinants of the disease are known to vary across patient populations. In India, cardiac diseases account for up to 10% of maternal deaths. At the same time, maternal iron deficiency (ID) with or without anaemia is highly prevalent in this population. However, the epidemiology of PPCM in India is poorly studied, and it is unknown whether maternal ID contributes to the risk of PPCM among Indian women. The DPhil project sought to address this knowledge gap by 1) reviewing the literature on the biomolecular mechanisms suggested for PPCM, 2) profiling the epidemiology of PPCM in a population of Indian women, 3) investigating the association between maternal iron status and PPCM among Indian women, and 4) comparing serum concentrations of prolactin to maternal iron status as a determinant of PPCM in Indian women.
Method: The project involved a systematic review of the biological mechanisms involved in the development of PPCM, formulation of an evidence-based framework for the role of ID in PPCM, and a secondary data analysis of a hospital-based case-control study of heart failure among mothers in India. The association of PPCM with serum concentrations of five iron indices and prolactin was compared between 44 pregnant and postpartum women diagnosed with PPCM (cases) and 170 postpartum women with no heart failure (controls). The classification accuracy of each marker was also assessed by the area under the receiver operating characteristic curve.
Results: The previously reported association between prolactin concentrations and PPCM could not be replicated. However, a new role for ID in PPCM was uncovered. Specifically, iron-deficient women were significantly more likely to be diagnosed with PPCM than those without ID (OR=4.54, 95% CI: 2.02, 10.9). Women diagnosed with PPCM had lower levels of transferrin saturation (TSAT) (p=0.021), higher soluble transferrin receptor (sTfR) levels indicative of cellular iron depletion (p=0.015), and decreased expression of the iron homeostatic hormone hepcidin, indicative of a compensatory iron mobilisation response (p<0.001). Among anaemic mothers, the odds of PPCM were significantly greater for those with ID than for those who had non-ID anaemia (OR=2.90, 95% CI: 1.05, 8.51). Concentrations of sTfR and hepcidin had the greatest value for distinguishing between women with and without PPCM (AUC=0.74 for both), while TSAT performed the poorest (AUC=0.63).
Conclusions: This study is the first to characterise the iron status of women diagnosed with PPCM in any population. The results have important implications for public health policies targeting ID in pregnant and postpartum women in India, and can also inform future research and clinical guidelines for the prevention, diagnosis and treatment of PPCM in this population.

Keywords: biomarkers
maternal health
India
peripartum cardiomyopathy
iron deficiency
heart failure
Advisor: Nair, M
Lakhal-Littleton, S
Kurinczuk, J