The Use of Novel Therapies in the Management of Haemolytic Disease of the Fetus and Newborn (HDFN): Scientific Impact Paper No. 75

Haemolytic disease of the fetus and newborn (HDFN) is a rare condition that causes a baby to develop anaemia while growing inside the woman; or after birth. Left untreated, this may lead to stillbirth or neonatal death. HDFN is caused when the pregnant woman's antibodies cross the placenta, enter the baby's circulation, and attach to proteins called antigens (inherited from the father) on the baby's haemoglobin containing red blood cells, and cause them to break apart, causing fetal anaemia. Women routinely have their blood tested at the start of pregnancy to assess their ABO blood group and Rh antigens. There are five main Rhesus antigens: D, C, c, E, e; with anti-D being responsible for most cases of HDFN. If a woman is found to be Rh D negative; a 'non-invasive' blood test is performed to assess if the fetal blood group is the same as the woman's. If a woman is found to be Rh D negative, and the baby is found to be D positive, the baby is at risk. This is because the baby has inherited the D antigen from the father; so-called Rhesus incompatibility. Other red blood cell antibodies such as anti-Kell or anti-Duffy can also cause fetal anaemia. Women at highest risk of developing HDFN are those who have had at least one previous birth or a sensitising event (such as abdominal trauma) in a current or previous pregnancy, causing the woman and baby's blood to mix. Current treatment for haemolytic disease of the fetus involves giving fetal blood transfusions, with a small risk of early labour or pregnancy loss. If anaemia develops later in pregnancy, early delivery of the baby may be recommended; which could lead to complications of prematurity. In cases of mild HDFN, the baby may only require light therapy for neonatal jaundice. However, if the anaemia occurs earlier in pregnancy and is severe, the baby may need blood transfusions while still in the womb - and after birth may require an exchange transfusion, to remove the woman's antibodies from their circulation and to treat the anaemia. Intravenous immunoglobulin (IVIG) is a potential non-invasive method to prevent or delay the onset of severe anaemia. It is a blood product given intravenously every week to women who have been deemed at very high risk of early onset HDFN. It can be started at the end of the first trimester until birth, or until anaemia develops. This paper will discuss the evidence behind IVIG and other novel therapies during pregnancy, including the risks and the benefits. The developers o