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Fetal RHD Screening in RH1 Negative Pregnant Women: Experience in Switzerland
Bernd Schimanski1, Rahel Kräuchi1, Jolanda Stettler1
1Interregional Blood Transfusion SRC Berne Ltd., 3008 Berne, Switzerland.
Insights
Noninvasive fetal RHD genotyping using maternal blood prevents unnecessary Rh immunoglobulin (RHIG) administration for RH1-negative mothers carrying RH1-negative fetuses. This screening optimizes RHIG use, conserving resources and reducing risks for pregnant women.
Area of Science:
- Immunology
- Genetics
- Maternal-Fetal Medicine
Background:
- RhD incompatibility between mother and fetus can lead to hemolytic disease of the fetus and newborn.
- Fetal RHD genotyping from maternal blood is recommended in Switzerland from 2020 to guide Rh immunoglobulin (RHIG) administration.
- Targeted RHIG administration ensures prophylaxis for RhD-negative women with RhD-positive fetuses.
Purpose of the Study:
- To evaluate the effectiveness and outcomes of noninvasive fetal RHD screening over 30 months in Switzerland.
- To determine the proportion of RhD-negative pregnant women who can avoid unnecessary RHIG administration.
- To assess the accuracy and reliability of in-house qPCR for fetal RHD genotyping.
Main Methods:
- Analysis of 7192 maternal plasma samples for cell-free fetal DNA.
- Extraction of cell-free DNA using a commercial kit.
- In-house quantitative PCR (qPCR) to detect RHD exons 5 and 7, with an amplification control.
Main Results:
- Valid RHD results were obtained for 7072 samples (98.2%).
- 64% of fetuses were RHD-positive, and 36% were RHD-negative.
- No false-negative results were observed; one false-positive result occurred. Inconclusive results were seen in 1.7% of samples.
Conclusions:
- Noninvasive fetal RHD screening effectively identifies fetuses that do not require RHIG, avoiding unnecessary treatment for over one-third of RhD-negative mothers.
- This approach reduces exposure to blood-derived products and conserves RHIG for women who genuinely need it.
- The study demonstrates the clinical utility and efficiency of fetal RHD genotyping in routine obstetric care.
Abstract:
RH1 incompatibility between mother and fetus can cause hemolytic disease of the fetus and newborn. In Switzerland, fetal RHD genotyping from maternal blood has been recommended from gestational age 18 onwards since the year 2020. This facilitates tailored administration of RH immunoglobulin (RHIG) only to RH1 negative women carrying a RH1 positive fetus. Data from 30 months of noninvasive fetal RHD screening is presented. Cell-free DNA was extracted from 7192 plasma samples using a commercial kit, followed by an in-house qPCR to detect RHD exons 5 and 7, in addition to an amplification control. Valid results were obtained from 7072 samples, with 4515 (64%) fetuses typed RHD positive and 2556 (36%) fetuses being RHD negative. A total of 120 samples led to inconclusive results due to the presence of maternal or fetal RHD variants (46%), followed by women being serologically RH1 positive (37%), and technical issues (17%). One sample was typed false positive, possibly due to contamination. No false negative results were observed. We show that unnecessary administration of RHIG can be avoided for more than one third of RH1 negative pregnant women in Switzerland. This reduces the risks of exposure to a blood-derived product and conserves this limited resource to women in actual need.
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