Versiti Blood Research Institute Articles
Innovative Research Helps to Protect Expectant Mothers and Their Unborn Babies
Debra Newman, PhD, studies fetal neonatal alloimmune thrombocytopenia (FNAIT), a disorder in which a pregnant mother develops antibodies to her unborn baby, resulting in dangerously low platelet counts in the baby.
Maci Safford was born in 2016 with bruising and critically low platelet counts, but otherwise appeared perfectly healthy. During her weeklong stay in the NICU, she was diagnosed with fetal neonatal alloimmune thrombocytopenia (FNAIT), a disease that affects approximately 1 in 350 pregnancies in the U.S. and causes severe complications in 1 in 1,000. “FNAIT is a disorder that arises when the immune system of a pregnant person makes antibodies against a baby’s platelets … resulting in dangerously low platelet counts in the baby before and immediately after birth,” said Versiti Blood Research Institute (VBRI) Senior Investigator Debra Newman, PhD.
Maci was lucky: she was diagnosed quickly and received specially matched platelets that boosted her platelet counts and allowed her to be discharged from the NICU. “Versiti Diagnostic Labs’ Platelet and Neutrophil Immunology Lab (PNIL) is a world-renowned resource for diagnosis of FNAIT in the U.S. and worldwide,” Dr. Newman said. “And thanks to its dedicated donor base, Versiti is an important source of the standard and specialty platelets that are needed for treatment of babies born with severe thrombocytopenia.” But what caused Maci to develop FNAIT in the first place?
Understanding the immune response
Platelets circulate in the bloodstream in an inactive state until they are activated by something like a cut, which causes them to form clots and prevent excessive bleeding. Sometimes, platelets are destroyed by B and T cells, which are immune cells that protect against infectious disease. “Our immune systems are designed to help us respond appropriately to infectious pathogens,” Dr. Newman said. “But an immune response can also cause a disease if it’s misdirected—like when the immune response is directed at tissues that we’d like it to leave alone.”
FNAIT results from one of these misdirected responses that occurs when the target of the pregnant mother’s immune system is her unborn baby’s tissues. The mother makes antibodies to her baby, resulting in the baby’s low platelet count.
Developing new tests to protect unborn babies and expectant mothers
Certain genetic markers can indicate which women might be at risk for developing FNAIT; however, not every mother with the pertinent genetic markers will have a baby with FNAIT. “We don’t test every pregnant woman for this risk, because we don’t know what to look for,” Dr. Newman said. “There’s no way of telling before it happens that FNAIT is going to be a problem.” Preemptive treatments also do not exist, and babies are only treated for FNAIT if they exhibit symptoms like low platelet counts and either overt bleeding or bruising.
“Our research is designed to try to develop a safe test that could identify if someone is developing the type of immune response that could cause FNAIT,” Dr. Newman said. “My goal is to gather information that can be used to justify a diagnostic test that would give people a warning.”
Propelling FNAIT research
Dr. Newman hopes to answer two questions through her research. The first is, what causes some cases of FNAIT to be more severe than others? The answer to this question has diagnostic implications, because if physicians can identify the features of specific antibodies that cause severe forms of FNAIT, they can screen for them in expectant mothers and identify patients at risk for complications.
“We need to do the research to see if the properties of these antibodies that we think are problematic, actually are,” she said. “If it’s true that there are certain types of antibodies that are problematic and we can test for them, the next step is to understand how these antibodies do what they do and what makes them dangerous.”
Second, Dr. Newman is interested in learning when the immune response develops during pregnancy. Understanding the timeline of the immune response would enable physicians to interrupt it and prevent the development of an immune response and the conditions that cause FNAIT.
The future of FNAIT research
“In research, you always have to keep one eye on the horizon and one eye firmly attached to the current project. We have to anticipate how the demand for knowledge is changing,” Dr. Newman said. “I see the potential for definitive diagnostic tests that can identify problem pregnancies safely and in every situation.”
In order to propel this type of groundbreaking research, Dr. Newman and her team rely on funding from the Versiti Blood Research Institute Foundation and competitive external grants. “If we could treat this disease in everybody, without having to wait and see if they develop the problem or not, that could potentially be a watershed discovery, especially for a place like Versiti with its expertise in this kind of testing,” she said.
“Versiti Blood Research Institute has faculty and staff who are immersed in science, enough to be aware of new technologies as they emerge,” she continued. “We have the facilities, equipment, resources and technical expertise to generate new resources for studying important problems with great speed. That puts us at a tremendous advantage for solving problems like FNAIT through research. It really does take a village, and I don’t think many people realize how much we all contribute to the understanding of a condition like this.”
About the expert: Debra Newman, PhD, is a senior investigator at Versiti Blood Research Institute and a professor in the Department of Pharmacology & Toxicology and the Department of Microbiology & Immunology at the Medical College of Wisconsin.