Dataset Information

The curse of the perinatal epidemiologist: inferring causation amidst selection.

ABSTRACT: Purpose of review:Human reproduction is a common process and one that unfolds over a relatively short time, but pregnancy and birth processes are challenging to study. Selection occurs at every step of this process (e.g., infertility, early pregnancy loss, and stillbirth), adding substantial bias to estimated exposure-outcome associations. Here we focus on selection in perinatal epidemiology, specifically, how it affects research question formulation, feasible study designs, and interpretation of results. Recent findings:Approaches have recently been proposed to address selection issues in perinatal epidemiology. One such approach is the ongoing pregnancies denominator for gestation-stratified analyses of infant outcomes. Similarly, bias resulting from left truncation has recently been termed "live birth bias," and a proposed solution is to control for common causes of selection variables (e.g., fecundity, fetal loss) and birth outcomes. However, these approaches have theoretical shortcomings, conflicting with the foundational epidemiologic concept of populations at risk for a given outcome. Summary:We engage with epidemiologic theory and employ thought experiments to demonstrate the problems of using denominators that include units not "at risk" of the outcome. Fundamental (and commonsense) concerns of outcome definition and analysis (e.g., ensuring that all study participants are at risk for the outcome) should take precedence in formulating questions and analysis approach, as should choosing questions that stakeholders care about. Selection and resulting biases in human reproductive processes complicate estimation of unbiased exposure- outcome associations, but we should not focus solely (or even mostly) on minimizing such biases.

SUBMITTER: Snowden JM

PROVIDER: S-EPMC6510491 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The curse of the perinatal epidemiologist: inferring causation amidst selection.

Snowden Jonathan M JM Bovbjerg Marit L ML Dissanayake Mekhala M Basso Olga O

Current epidemiology reports 20180927 4

<h4>Purpose of review</h4>Human reproduction is a common process and one that unfolds over a relatively short time, but pregnancy and birth processes are challenging to study. Selection occurs at every step of this process (e.g., infertility, early pregnancy loss, and stillbirth), adding substantial bias to estimated exposure-outcome associations. Here we focus on selection in perinatal epidemiology, specifically, how it affects research question formulation, feasible study designs, and interpre ...[more]

PMID: 31086756

Similar Datasets

Project description:Epitope mapping studies aim to identify the binding sites of antibody-antigen interactions to enhance the development of vaccines, diagnostics and immunotherapeutic compounds. However, mapping is a laborious process employing time- and resource-consuming ‘wet bench’ techniques or epitope prediction software that are still in their infancy. For polymorphic antigens, another challenge is characterizing cross-reactivity between epitopes, teasing out distinctions between broadly cross-reactive responses, limited cross-reactions among variants and the truly type-specific responses. A refined understanding of cross-reactive antibody binding could guide the selection of the most informative subsets of variants for diagnostics and multivalent subunit vaccines. We explored the antibody binding reactivity of sera from human patients and Peromyscus leucopus rodents infected with Borrelia burgdorferi to the polymorphic outer surface protein C (OspC), an attractive candidate antigen for vaccine and improved diagnostics for Lyme disease. We constructed a protein microarray displaying 23 natural variants of OspC and quantified the degree of cross-reactive antibody binding between all pairs of variants, using Pearson correlation calculated on the reactivity values using three independent transforms of the raw data: (1) logarithmic, (2) rank, and (3) binary indicators. We observed that the global amino acid sequence identity between OspC pairs was a poor predictor of cross-reactive antibody binding. Then we asked if specific regions of the protein would better explain the observed cross-reactive binding and performed in silico screening of the linear sequence and 3-dimensional structure of OspC. This analysis pointed to the C-terminal helix of the structure as a major determinant of type-specific cross-reactive antibody binding. We developed bioinformatics methods to systematically analyze the relationship between local sequence/structure variation and cross-reactive antibody binding patterns among variants of a polymorphic antigen, and this method can be applied to other polymorphic antigens for which immune response data is available for multiple variants.

Dataset Information

The curse of the perinatal epidemiologist: inferring causation amidst selection.

Publications

The curse of the perinatal epidemiologist: inferring causation amidst selection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure