PURLs

A new protocol for RhD-negative pregnant women?

J Fam Pract. 2018 May;67(5):306,308,319

References

1. de Haas M, Thurik FF, van der Ploeg CP, et al. Sensitivity of fetal RHD screening for safe guidance of targeted anti-D immunoglobulin prophylaxis: prospective cohort study of a nationwide programme in the Netherlands. BMJ. 2016;355:i5789.

2. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 75: Management of alloimmunization during pregnancy. Obstet Gynecol. 2006;108:457-464. 

3. Urbaniak S, Greiss MA. RhD haemolytic disease of the fetus and the newborn. Blood Rev. 2000;14:44-61.

4. Mayne S, Parker JH, Harden TA, et al. Rate of RhD sensitisation before and after implementation of a community based antenatal prophylaxis programme. BMJ. 1997;315:1588-1588.

5. MacKenzie IZ, Bowell P, Gregory H, et al. Routine antenatal Rhesus D immunoglobulin prophylaxis: the results of a prospective 10 year study. Br J Obstet Gynecol: 1999;106:492-497.

6. Zolotor AJ, Carlough MC. Update on prenatal care. Am Fam Physician. 2014;89:199-208.

7. Mackie FL, Hemming K, Allen S, et al. The accuracy of cell-free fetal DNA-based non-invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta-analysis. BJOG. 2017;124:32-46.

8. Committee on Practice Bulletins-Obstetrics. Practice Bulletin No. 181: Prevention of Rh D Alloimmunization. Obstet Gynecol. 2017;130:e57-e70.

9. National Institute for Health and Care Excellence. High-throughput non-invasive prenatal testing for fetal RHD genotype 1: Recommendations. Available at: https://www.nice.org.uk/guidance/dg25/chapter/1-Recommendations. Accessed August 9, 2017.

10. Hawk AF, Chang EY, Shields SM, et al. Costs and clinical outcomes of noninvasive fetal RhD typing for targeted prophylaxis. Obstet Gynecol. 2013;122:579-585.

STUDY SUMMARY

Cell-free DNA test gets high marks in Netherlands trial

This large observational cohort trial from the Netherlands examined the accuracy of identifying RhD-positive fetuses using cell-free DNA isolates in maternal plasma. Over the 15-month study period, fetal RhD testing was conducted during Week 27 of gestation, and results were compared with those obtained using neonatal cord blood at birth. If the fetal RhD test was positive, providers administered 200 mcg anti-D immunoglobulin during the 30th week of gestation and within 48 hours of birth. If fetal RhD was negative, providers were told immunoglobulin was unnecessary.

Fetal RhD testing at 27 weeks’ gestation appears highly accurate and could reduce the unnecessary use of anti-D immunoglobulin when the fetal RhD is negative.

More than 32,000 RhD-negative women were screened. The cell-free DNA test showed fetal RhD-positive results 62% of the time and RhD-negative results in the remainder. Cord blood samples were available for 25,789 pregnancies (80%).

Sensitivity, specificity. The sensitivity for identifying fetal RhD was 99% and the specificity was 98%. Both negative and positive predictive values were 99%. Overall, there were 225 false-positive results and 9 false-negative results. In the 9 false negatives, 6 were due to a lack of fetal DNA in the sample and 3 were due to technical error (defined as an operator ignoring a failure of the robot pipetting the plasma or other technical failures).

The false-negative rate (0.03%) was lower than the predetermined estimated false-negative rate of cord blood serology (0.25%). In 22 of the supposed false positives, follow-up serology or molecular testing found an RhD gene was actually present, meaning the results of the neonatal cord blood serology in these cases were falsely negative. If you recalculate with these data in mind, the false-negative rate for fetal DNA testing was actually less than half that of typical serologic determination.

WHAT’S NEW

An accurate test with the potential to reduce unnecessary Tx

Fetal RhD testing at 27 weeks’ gestation appears to be highly accurate and could reduce the unnecessary use of anti-D immunoglobulin when the fetal RhD is negative.

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