Hemolytic disease of the fetus and newborn (HDFN) is unknown to most people, but it has caused struggles for Andrea Renzi for years. The disease affected two of her five children—and has turned her into an activist on behalf of other women touched by HDFN.
Renzi, who lives in Nashua, NH, helps run ISO Moms, a Facebook network for women diagnosed with red blood cell antibodies. Created 13 years ago, the group now has 2700 members. ISO—short for isoimmunization—refers to the Rh-negative mother’s development of antibodies against the paternal Rh antigen on fetal red blood cells.
Its sign-up page states: “We understand what you are going through and how scary an initial diagnosis of alloimmunization is. The purpose of this group is help support one another, lift each other up, and let everyone know they are not alone in their ISO journey.” Alloimmunization is another term for isoimmunization.
A smaller group moderated solely by Renzi, the Alloimmunization Support Network, has 627 members and is for anyone—including friends and family—affected by the disease.
“We help our families advocate for themselves because without care standards, a baby that’s born with a normal hemoglobin might fall through the cracks,” she said. “We have seen babies die from late‑onset anemia because of this. I don’t want to see any more families destroyed.”
Renzi, 39, recently spoke to Rare Disease Advisor—a sister brand of HDFN Companion—about HDFN, which arises when would-be mothers have a blood type that’s incompatible with that of their unborn child, with potentially fatal consequences.
“My body created antibodies similar to how it would against a virus or bacteria. However, it was against my babies’ blood type,” she explained. “What happens with this disease is your babies become anemic, and they’re also affected by hyperbilirubinemia. We always tell parents that’s not dangerous, but at high levels, it’s actually very dangerous. It can cause hearing loss, cerebral palsy, and tooth enamel hypoplasia.”
Renzi said the disease changed the course of her pregnancies with son Jacob, now 10, and daughter Morgan, now 7.
“It meant monitoring twice, sometimes three times a week. It meant early deliveries and monitoring post‑birth. Our babies had to have frequent blood draws—the first few days, every six to eight hours, then daily, then after a week, we were able to go two and then three days between blood draws. Then it was weekly for the next three months.”
What is bilirubin?
Bilirubin is a molecular byproduct of the breakdown of hemoglobin, the protein responsible for holding the oxygen transported in red blood cells. It is normally transported to the liver, where it undergoes a transformation called conjugation, and is then excreted from the body through the intestines. Jaundice is caused by the accumulation of bilirubin in the blood, which is known as hyperbilirubinemia.
The first sign that anything was wrong, Renzi recalled, was when she was pregnant with Jacob and went for her normal 28-week screening for gestational diabetes. Her obstetrician happened to be out of town at a conference, and another physician caught her positive antibody screening.
“She called me and said, ’I don’t really know what this is, but it looks like we need to do more blood work,’” Renzi recalled. “I started to research what it meant and told her I also needed a referral to maternal-fetal medicine.”
Her doctor put the referral in, but meanwhile, Renzi’s antibody levels continued to rise.
Listen to a Rare Disease Advisor podcast with Andrea Renzi
Once they reached potentially dangerous critical levels, Renzi had to travel weekly to Boston for ultrasound screenings to detect fetal anemia. Jacob was born at 37 weeks, weighing 5 pounds.
“They tested his umbilical cord blood, and he was not anemic, but he did have high bilirubin,” she said “They didn’t opt to treat at that time. I wasn’t aware until I learned more later that they should have treated him.”
Renzi has antibodies to the C antigen of the Rh blood group, though the on-call pediatrician didn’t understand at the time why that might have been a problem. Fortunately, a hospital nurse remembered something about HDFN from a college textbook and ordered new blood work.
Barely three days old, Jacob’s bilirubin level was just under 16 mg/dL. The infant was clearly jaundiced and required phototherapy—or light treatment—to help get rid of excess bilirubin. Due to the rhC antibodies, though, his levels remained higher than normal for nearly four months, even after he was discharged from phototherapy and the neonatal intensive care unit.
“He was followed by pediatric hematology at Boston Children’s [Hospital],” she said. “His hematologist there was completely on top of things, and she co-managed care with his normal pediatrician. They were phenomenal.”
Read more about the HDFN care team
Three years later, when Renzi was pregnant with Morgan, she thought things would be different. The baby girl was born at 36 weeks, and quickly reached bilirubin levels so high that a blood transfusion was deemed urgent. But after a few hours of phototherapy, her bilirubin dropped quickly and no transfusion ever took place.
Morgan is now healthy. Jacob, his mother said, struggles with mild hypotonia and has had hearing problems. Both children had severe enamel hypoplasia from the bilirubin. Lucas, 13, had some issues with bilirubin as well.
“It’s upsetting to me that there’s still not a care standard. The American Academy of Pediatrics updated its treatment guidelines in 2022, and I was actually involved in reviewing them,” she said. “But we don’t yet know how that’s going to affect babies with HDFN. It’ll probably be some years before we know.”
