Determination of Fetal Rhesus D Status from Maternal Plasma of Rhesus Negative Women

Approximately 15 percent of Norwegian women are Rhesus D (RhD)-negative. During pregnancy and birth, there is a danger that these women produce antibodies against fetal blood cells (alloimmunization), if the fetus is RhD-positive. These antibodies may cross the placenta and cause hemolytic disease of the fetus, which may become life threatening. Today, all RhD-negative pregnant women are closely followed-up during pregnancy, and the newborns are routinely tested for RhD-type at birth. Upon detection of an RhD-positive child, the mother will get anti-D prophylaxis within 72 hours after birth to prevent the formation of anti-D antibodies that may cause problems in subsequent pregnancies.Alloimmunization may occur throughout the whole pregnancy, especially during the last trimester. Therefore, in the Guidance for obstetrics 2014 published by the Norwegian Gynecological Association, it is recommended that anti-D prophylaxis should be offered RhD-negative women also during pregnancy, if they carry an RhD-positive fetus. With a blood sample from the pregnant woman, it can be tested whether the fetus is RhD-negative or -positive. The technology is based on analysis of free fetal DNA present in the woman's blood during pregnancy, and is often referred to as non-invasive prenatal testing (NIPT). The result of NIPT can be used to provide targeted prophylactic treatment to the pregnant women who can benefit from it, and to avoid unnecessary treatment of pregnant women with RhD negative fetuses.In this report, we summarize research studies on diagnostic accuracy of NIPT, as well as clinical effectiveness and health economic and ethical consequences of introducing NIPT for fetal RhD typing in all RhD-negative pregnant women. The main findings are:Diagnostic accuracy It is likely that NIPT gives a very accurate RhD typing of the fetus. The documentation is of high quality. Clinical effectiveness We identified no systematic reviews on clinical effectiveness of introducing NIPT for fetal RhD typing in all RhD-negative pregnant women. Health economic evaluation Introduction of a program with NIPT-guided anti-D prophylaxis will give an additional cost of approximately 4 million Norwegian kroner per year. The cost per avoided RhD-alloimmunization is approximately 106,000 Norwegian kroner. These numbers are based on effectiveness data from a Swedish cohort study. Ethics NIPT is an ethically controversial technology. NIPT for RhD typing, when used after the legal time limit for abortion has passed, avoids many of the ethical issues, but alternative or extended applications may be ethically challenging.