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Multicenter Study
. 2014 Sep 4:349:g5243.
doi: 10.1136/bmj.g5243.

Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study

Lyn S Chitty  1 , Kirstin Finning  2 , Angela Wade  3 , Peter Soothill  4 , Bill Martin  5 , Kerry Oxenford  6 , Geoff Daniels  2 , Edwin Massey  2
Affiliations
Multicenter Study

Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study

Lyn S Chitty et al. BMJ. .

Abstract

Objectives: To assess the accuracy of fetal RHD genotyping using cell-free fetal DNA in maternal plasma at different gestational ages.

Design: A prospective multicentre cohort study.

Setting: Seven maternity units in England.

Participants: RhD negative pregnant women who booked for antenatal care before 24 weeks' gestation.

Interventions: Women who gave consent for fetal RHD genotyping had blood taken at the time of booking for antenatal care and, when possible, at other routine visits such as for Down's syndrome screening between 11 and 21 weeks' gestation, at the anomaly scan at 18-21 weeks, and in the third trimester when blood was taken for the routine antibody check. The results of cord blood analysis, done routinely in RhD negative pregnancies, were also obtained to confirm the fetal RHD genotyping.

Main outcome measures: The accuracy of fetal RHD genotyping compared with RhD status predicted by cord blood serology.

Results: Up to four analyses per woman were performed in 2288 women, generating 4913 assessable fetal results. Sensitivity for detection of fetal RHD positivity was 96.85% (94.95% to 98.05%), 99.83% (99.06% to 99.97%), 99.67% (98.17% to 99.94%), 99.82% (98.96% to 99.97%), and 100% (99.59% to 100%) at <11, 11-13, 14-17, 18-23, and >23 completed weeks' gestation, respectively. Before 11 weeks' gestation 16/865 (1.85%) babies tested were falsely predicted as RHD negative.

Conclusions: Mass throughput fetal RHD genotyping is sufficiently accurate for the prediction of RhD type if it is performed from 11 weeks' gestation. Testing before this time could result in a small but significant number of babies being incorrectly classified as RHD negative. These mothers would not receive anti-RhD immunoglobulin, and there would be a risk of haemolytic disease of the newborn in subsequent pregnancies.

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Conflict of interest statement

Funding: This study was funded by the National Institute for Health Research, Research for Patient Benefit Programme (PB-PG-0107-12005), and Howard Ostin Trust (Project No 011). LSC is partially funded by the Great Ormond Street Hospital Children’s Charity and the NIHR Biomedical Research Centre at Great Ormond Street Hospital. The funded research is independent and the views expressed in the paper are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Maternity care pathway followed in England by gestational age together with number of women tested at each completed week of gestation. Dark bars indicate recommended gestations for tests but not all women book early in pregnancy and some attend late for their anomaly scan, so lighter bars show extended range of gestations, when women might have been recruited when attending for these indications
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Fig 2 Sensitivity of determining RHD positive fetuses according to gestational age (inconclusive results treated as RHD positive). Fitted model (solid line) and 95% bootstrap confidence intervals (dashed lines) obtained from generalised linear model incorporating random intercept to take into account repeat measures from same women over pregnancy. Weekly estimates are overlaid with point size proportional to number of women tested during each week
See this image and copyright information in PMC

Comment in

References

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