Potential of a Second Screening Test for Alloimmunization in Pregnancies of Rhesus-positive Women: A Swedish Population-based Cohort Study

Introduction: There is lack of consensus regarding whether a second screening in rhesus-positive pregnant women is worthwhile, with different guidelines, recommendations, and practices. We aimed to estimate the number and timing of missed alloimmunizations in rhesus-positive pregnancies screened once and weigh the relative burden of additional screening and monitoring versus the estimated reduction in adverse pregnancy outcomes. Methods: We extracted information on maternal, pregnancy, and screening results for 682,126 pregnancies for 2003–2012 from Swedish national registers. We used data from counties with a routine second screening to develop and validate a logistic model for a positive second test after an earlier negative. We used this model to predict the number of missed alloimmunizations in counties offering only one screening. Interval-censored survival analysis identified an optimal time window for a second test. We compared the burden of additional screening with estimated adverse pregnancy outcomes avoided. Results: The model provided an accurate estimate of positive tests at the second screening. For counties with the lowest screening rates, we estimated that a second screening would increase the alloimmunization prevalence by 33% (from 0.19% to 0.25%), detecting the 25% (304/1222) of cases that are currently missed. The suggested timing of a second screen was gestational week 28. For pregnancies currently screened once, the estimated cost of a second test followed by maternal monitoring was approximately 10% of the cost incurred by the excess adverse pregnancy outcomes. Conclusion: Investment in routine second screening can identify many alloimmunizations that currently go undetected or are detected late, with the potential for cost savings.