Methodologic Issues in the Study of the Relationship between Histologic Indicators of Intraamniotic Infection and Clinical Outcomes

GoalTo determine the structure of the relationships of the histology scores for acute intraamniotic infection collected in the Collaborative Perinatal Project (CPP).Materials and Methods44,427 subjects of the CPP had complete histology scores available for the 9 measures that related to acute intraamniotic infection (i.e., neutrophil infiltrates in umbilical cord, amnion of extraplacental membranes and chorionic plate, decidua, chorionic plate and fetal chorionic vessels). Confirmatory factor analysis was used to determine the relationships among the different markers of maternal inflammatory responses (in amnion, chorion and decidua) and fetal inflammatory responses (in umbilical cord and fetal chorionic vessels).ResultsA single CFA model could not be developed across all CPP sites. A well-fit model was developed from the Boston site (N = 10,803) and the factor loadings applied to the histology scores from the other CPP sites. The resultant scores for the latent variables (maternal and fetal inflammatory responses) were compared across sites. There was not only considerable variability in factor loadings, and the signs of factor loadings were also inconsistent across sites.ConclusionHistopathology scores of neutrophil infiltrates performed by different observers do not have the same interrelationships and, by extension, the latent variables they are supposed to reflect may not be equivalent. The lack of measurement invariance renders their use as indicators of the underlying processes of maternal and fetal inflammatory responses problematic in analysis with any clinical outcome.