Comparison of dried blood spot and plasma sampling for untargeted metabolomics.

INTRODUCTION: Untargeted metabolomics holds significant promise for biomarker detection and development. In resource-limited settings, a dried blood spot (DBS)-based platform would offer significant advantages over plasma-based approaches that require a cold supply chain. OBJECTIVES: The primary goal of this study was to compare the ability of DBS- and plasma-based assays to characterize maternal metabolites. Utility of the two assays was also assessed in the context of a case-control predictive model in pregnant women living with HIV. METHODS: Untargeted metabolomics was performed on archived paired maternal plasma and DBS from n = 79 women enrolled in a large clinical trial. RESULTS: A total of 984 named biochemicals were detected across both plasma and DBS samples, of which 627 (63.7%), 260 (26.4%), and 97 (9.9%) were detected in both plasma and DBS, plasma alone, and DBS alone, respectively. Variation attributable to study individual (R2 = 0.54, p < 0.001) exceeded that of the sample type (R2 = 0.21, p < 0.001), suggesting that both plasma and DBS were capable of differentiating individual metabolomic profiles. Log-transformed metabolite abundances were strongly correlated (mean Spearman rho = 0.51) but showed low agreement (mean intraclass correlation of 0.15). However, following standardization, DBS and plasma metabolite profiles were strongly concordant (mean intraclass correlation of 0.52). Random forests classification models for cases versus controls identified distinct feature sets with comparable performance in plasma and DBS (86.5% versus 91.2% mean accuracy, respectively). CONCLUSION: Maternal plasma and DBS samples yield distinct metabolite profiles highly predictive of the individual subject. In our case study, classification models showed similar performance albeit with distinct feature sets. Appropriate normalization and standardization methods are critical to leverage data from both sample types. Ultimately, the choice of sample type will likely depend on the compounds of interest as well as logistical demands.

Correlates of early breastfeeding cessation and breastmilk expression in Uganda: a case-control study.

OBJECTIVE: To identify the correlates of early breastfeeding (BF) cessation and breastmilk expression (BE) among mothers 12 months after childbirth. METHODS: We used a case-control study design to compare characteristics between mothers who stopped BF and expressed breastmilk 12 months after childbirth in Uganda. BF practices were determined in 12-month follow-up interviews using an adapted World Health Organization infant feeding questionnaire. Univariate and bivariate logistic regression models identified correlates of early BF cessation and BE as distinct but related outcomes. RESULTS: The odds of early BF cessation were higher among mothers who expressed breastmilk irrespective of maternal age (adjusted odds ratio: 2.82; 95% confidence interval: 1.39, 5.68). Mothers who stopped BF and did not express breastmilk were more likely to be older than those who continued BF and did not express breastmilk during the first 12 postpartum months. CONCLUSION: Mothers living with human immunodeficiency virus infection have disproportionately high odds of early BF cessation that may contribute to disparities in child health outcomes. Promotion of safe BF practices coupled with family and social support could be a viable preventive strategy for attenuating such disparities, especially among young mothers at risk of early BF cessation.