Background Peripartum cardiomyopathy (PPCM) is a complication of pregnancy in which symptoms of heart failure with reduced ejection fraction (<45%) develop during pregnancy or shortly after delivery. The aetiology and pathophysiology of the disease are poorly understood, but there is some evidence that PPCM is associated with a) altered levels of prolactin (PRL) cleavage products, and b) anaemia. However, the strength of the evidence has not been systematically ascertained. We conducted a systematic review and meta-analysis to: 1) assess the strength of the evidence for PRL cleavage and iron deficiency anaemia as mechanisms for PPCM, 2) identify other biomarkers associated with PPCM.

Methods The search strategy for the systematic review was a mix of automated and manual searches, and included both published and unpublished literature. We included observational studies from across the world reporting levels of laboratory biomarkers in women diagnosed with PPCM and in controls without pre-existing CVD, without any restriction of language or time-period. We assessed the risk of bias and quality of the evidence across studies using standard tools. Pooled Standardized Mean Difference (SMD) were generated using a random effects model for the difference in levels of biomarkers comparing PPCM cases to healthy controls.

Results Out of 2,425 unique research articles, 78 were selected for full text screening. We extracted 31 papers, 16 of which were included in the meta-analysis. Two papers assessed the association of PRL with PPCM and reported that PPCM cases had higher levels of total PRL. Other markers investigated in PPCM patients included inflammatory markers, markers of myocardial dysfunction, vascular markers, and micronutrients. Generally, PPCM cases had higher serum levels of CRP (SMD: 2.281, 95% CI: 0.114; 4.448), white blood cells (SMD: 0.437, 95% CI: 0.095; 0.778), natriuretic peptides (SMD: 3.453, 95% CI: 2.174; 4.695), cardiac troponins (SMD: 1.108, 95% CI: 0.690; 1.526), liver enzymes (SMD: 0.651, 95% CI: 0.075; 1.228), and creatinine (SMD: 0.513, 95% CI: 0.33; 0.694), but lower levels of albumin (SMD: -0.662, 95% CI: -0.971; -0.352), selenium (SMD: -0.744, 95% CI: -1.485; -0.002), and haemoglobin (SMD:-0.449, 95% CI: -0.639; -0.259). We did not find any studies that analysed the association between levels of iron markers and PPCM.

Conclusion More robust epidemiologic studies are needed to strengthen the link between PRL and PPCM, identify new molecular pathways involved in the development and progression of PPCM, and elucidate the role of iron status in the pathophysiology of the disease.