Pregnancy-Specific Reference Intervals For C-Reactive Protein Improve Diagnostic Accuracy For Infection: A Longitudinal Study

Background and aims: Infections are a major cause of maternal mortality. C-reactive protein (CRP), a commonlyused inflammatory marker, is widely used to inform diagnosis, but the upper limit of normal in pregnancy is uncertain. We have defined trimester-specific reference intervals for CRP and evaluated their diagnostic accuracy for infection.Materials and methods: Development cohort: longitudinal study of pregnant women to determine 95% reference intervals. Evaluation cohort: diagnostic accuracy study to evaluate these intervals in 50 women with suspected intrauterine infection.Results: In these 322 healthy pregnant women, CRP was substantially higher than in most non-pregnant populations. CRP was similar in each trimester, with an upper reference limit of 19 mg/L. CRP increased linearly with body mass index (p < 0.0001).The sensitivity and specificity of CRP for diagnosing chorioamnionitis were 73% and 86%, respectively. The overall diagnostic accuracy using the pregnancy-specific reference interval was significantly better than that of the existing standard (p = 0.03).Conclusions: CRP is a widely-used clinical tool in pregnancy, and a pregnancy-specific reference interval should be used to optimise diagnostic accuracy. Chorioamnionitis was used as an example of a localised infection with well-defined outcomes, but pregnancy-specific RIs for CRP should be considered in any clinical setting including pregnant women.