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Born Free Method: The PodcastWomen's health...reimagined. Author: Nathan Riley, MD, Father of 2
There are a lot of birth-related podcasts out there. But here you are...considering this one! As with all of our projects at Born Free Method, this project is one of a kind. If you are fed up with modern maternity care, stop grumbling and groaning and take action! This podcast can lead the way. Somehow we manage to blend birth, spirituality, medicine, fitness, ecology, ceremony, psychedelia, psychology, and more all into one great offering, leaving a lingering whiff of "my body, my choice" in our wake. We're happy that you're here for the show! nathanrileyobgyn.substack.com Language: en Genres: Health & Fitness, Medicine, Society & Culture Contact email: Get it Feed URL: Get it iTunes ID: Get it Trailer: |
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The Skinny on Rhesus factor (Rh) and Anti-D therapy (Rhogam)
Friday, 6 November, 2026
Hemolytic disease of the newborn (HDN) was first described in 1609 by a French midwife. It took centuries of case reports to find a potential cause. A 1939 study out of JAMA by Levine, et al, was the first report on blood compatibility as the culprit, and then in 1940 Landsteiner and Wiener identified the specific protein responsible. They named it “Rh factor” after the rhesus monkey cells that were used in their experiments. It wasn’t until anti-D antibody, aka Rhogam, was introduced in 1968 that we began to see a sharp decline in HDN. I will present the basic process as told by the conventional model of obstetrics and midwifery and along with some welcome criticisms of this story. As a foreward, this is not by any stretch a systematic review of every study that has ever been published on this topic. But it’s a start…The Conventional StoryRhesus factor, also known as D-antigen or Rh-factor, is a protein found on the surface of red blood cells (RBCs). If your blood type is “negative” (e.g. O negative, A negative, B negative, AB negative), your RBCs don’t have this protein. If your blood type is “positive (e.g. O positive, A positive, B positive, AB positive), your RBCs have this protein on their surface. Your RBCs are floating around in your blood stream, and if an antigen like D is sitting on their surface, your immune system will recognize the antigen as “self” and you won’t mount an immune response. If such an antigen is introduced into the blood stream of a person without this antigen on her RBCs, during childbirth, for example, her immune system can recognize the foreign protein (antigen) and remember it through a series of chemical messengers. This memory is referred to as “alloimmunization”. In subsequent exposures, like future pregnancies, her immune system will mount a robust immune response to the foreign D-antigen through the production of antibodies that can destroy cells with D attached. This is one potential issue with blood transfusion that is mitigated by a process called crossmatching, which ensure that the new blood doesn’t contain RBCs with foreign antigens. In pregnancy, a baby with a “positive” blood type growing within a mother with a “negative” blood type and who has become alloimmunized against D-antigen can be susceptible to attack on the part of their D-antigen displaying RBCs, as those anti-D antibodies can cross the placenta. As such, that unborn baby’s RBCs can be destroyed by mother’s immune system, causing hemolytic disease of the newborn (HDN), which results in very watery blood that flows more swiftly through the baby’s circulatory system and accumulation of into tissues, leading to a condition known as fetal hydrops, which is often fatal. There are interventions to prevent fetal death, however.To prevent this process, a pregnant woman in the United States who has not been alloimmunized will be offered a dose of anti-D antibody (aka Rhogam) around 28 weeks and again within 72 hours of birth. Rhogam works by masking the D-antigen on the fetal RBCs from the mother’s immune system, thereby preventing the immune response that leads to alloimmunization. If the father also has Rh-negative blood, then all of the babies conceived by him and his wife will also be Rh negative. If the father is Rh-positive, then there is a roughly 75% chance that any baby conceived between him and his Rh-negative wife will also have a Rh-positive blood type and thus Rhogam may be beneficial. If you are an Rh-negative mother carrying an Rh-positive baby, there is a reportedly 1-in-7 (14%) chance of alloimmunization if you decline Rhogam. In subsequent pregnancies of alloimmunized mothers, roughly 20-25% of babies will develop some degree of HDN. In severe HDN (determined largely on ultrasound studies of the middle cerebral artery performed by high-risk OBGYNs called maternal fetal medicine (MFM) specialists), blood transfusion will be recommended for the baby while the baby is still inside the uterus. This is done directly into the umbilical vein with a long needle through the abdominal wall. For clarity’s sake, first pregnancies are rarely affected by alloimmunization and fetal hydrops. The exception is when an Rh-negative woman is previously exposed to D-antigen through poorly crossmatched blood in the event that she received a blood transfusion. Otherwise, the “memory” phase occurs during a pregnancy or birth in which a bunch of Rh-positive fetal blood crosses over into maternal circulation. If alloimmunization occurs, those anti-D antibodies can cross the placenta in future pregnancies and harm the baby by destroying its blood cells. There are a number of studies dating back over 50 years to support this story:* Freda 1964, Transfusion* Freda 1966, Science* Clarke 1963, BMJ (PMC)* Cochrane postpartum review in PMC* Bowman 1978, CMAJ* Tovey 1983, Lancet* PLOS ONE systematic review* Targeted antenatal anti-D systematic reviewCriticisms of this storyThe basic mechanism of alloimmunization doesn’t have a lot of critics, but the critical thinker might have a few important questions. Cochrane reviewers noted that the randomized trials of Rhogam were small and low-quality, and if this intervention does indeed save lives, it would be unethical to withhold it in a robust randomized, double-blind, placebo-controlled trial, so like with many questions in obstetrics, we are forced to rely on observational data to drive counseling and policy. * Why do the dosage and timing of anti-D antibody in the United States differ with other countries like those in the UK?* Dosing has not been studied as well as efficacy. If this technology works, then what’s the minimum effective dose? In the US, two 300-µg doses are given, the first at 28 weeks and the second within 72 hrs postpartum. In the UK, a dose of 100-µg is given at 28 weeks and a second 100-µg dose is given at 34 weeks. After birth in the UK, an additional dose of 100-µg is administered but only if the baby is found to be Rh positive. Additional Rhogam may be administered based on Kleihauer testing. In both the US and UK, Rhogam is only offered in the event of a negative antibody screen prior to administration. * Quick note: Kleihauer testing involves taking a sample of blood from a pregnant woman and measuring the percentage of RBCs in that sample that came from the fetus. This is a rudimentary means of determining how many fetal RBCs passed into the mother’s circulation during a miscarriage, subchorionic hemorrhage, or the birth itself, all of which carry the risk of maternal-fetal blood mixing, which is how the mother’s immune system gets exposed to fetal RBCs in the first place.* The big stink to this answer is that these two regimens - or any other regimen, for that matter - haven’t been compared head to head. Even observational data is scant, but from what we can gather, they’re comparable in efficacy from an absolute risk standpoint. The reason we use a bigger dose in the United States is due to the additional work and cost of Kleihauer testing and then determining the appropriate dose based on that result. So we use a bigger dose of 300-µg which is thought to be sufficient to cover any amount of maternal-fetal RBC mixing. Interestingly, even a 50-µg dose was found to be effective according to Cochrane reviewers (link above) when compared to 100-µg. A primary issue with studying “failure” rates of Rhogam at different doses is that the failure rate is so low that a sufficiently powered study to detect differences in groups receiving different doses would have to be so large that it would be very costly to complete. * Lastly, most if not all of these studies were designed to determine whether Rhogam administration prevented alloimmunization, not HDN, and the methods used to detect anti-D antibodies in maternal circulation aren’t perfect nor is pre… Get full access to Born Free Method: The Podcast at nathanrileyobgyn.substack.com/subscribe
