LUMC sheds new light on treatment babies with rhesus disease with international database
&w=710&h=710)
In rhesus disease, also known as hemolytic disease of the fetus and newborn, a rhesus D-negative mother's immune system attacks her baby's rhesus D-positive blood, which can lead to severe anemia. This usually occurs only after a previous pregnancy with a rhesus D-positive baby, when the mother has developed antibodies.
LUMC is a global expert on rhesus disease. The hospital is also the national fetal therapy referral center. This means that pregnant women from all over the country come to LUMC for treatments of the unborn child. As a result, LUMC always has a good overview of all treatment options. Much has also been published about this over the past few decades.
“We thought we had reached the point where we actually knew everything; that there was almost nothing left to improve. At the same time, we didn't actually believe that. So we wanted to know: what is the rest of the world actually doing? And that's why we set up this study,” says LUMC researcher Derek de Winter (photo).
[The text continues below the block]
31 centers from 22 countries
The DIONYSUS study examined what treatments for rhesus disease exist in the world and how they are used. The study involved 31 centers from 22 countries, mainly in Europe, but also in North and South America, Africa and Asia. They shared their treatment data with LUMC. It was then up to De Winter to compile this gigantic bulk of information into one joint database. The results were recently published in The Lancet Haematology and JAMA Network Open.1,2
These data were all pseudonymous, data that could only be traced indirectly. In total, that yielded data from about 2,400 pregnancies. About 4% of those pregnancies resulted in infant mortality. Two thirds of these died from rhesus disease, often due to hydrops (accumulation of fluid in different parts of the fetus' body) or severe anemia, usually because they had been referred too late to a center of expertise.
Big difference between centers
That data showed that care around rhesus disease varies widely between countries and centers. De Winter, “There appeared to be differences in almost all aspects of care, from referral and monitoring to treatment techniques, timing and frequency of treatments, such as intra-uterine transfusions. This study has really broadened our perspective.” Based on the findings, several new international studies have been launched to narrow treatment differences between centers, two of which were recently published.3,4
The researchers also found out that there is a very big difference between what is known about rhesus disease, for example, much is known in America and Europe, while there is no to little data available from Africa 
and Southeast Asia. For that reason, AFRICARhE was set up, a collaboration
between centers in Tanzania, Ethiopia and Malawi, the LUMC and Sanquin. Their goal is to gain more knowledge about the situation in African countries and explore ways to prevent the disease there.5
Gynecologist Joanne Verweij (photo) is the initiator of this project. “In Tanzania, but also in Malawi and Ethiopia, it is not, or not well, known how often rhesus disease occurs.
Registration is lacking.That's why we call it a hidden disease.
Yet the disease is simple to prevent with anti-D. Together with colleagues from Ethiopia, Tanzania and Malawi, we have set up studies to gain knowledge about the disease. “6
Extending the length of pregnancy
Another insight was about the length of gestational age at birth.
De Winter: “Our standard was to have a baby with severe rhesus disease born between 36 and 37 weeks. With the idea that the longer the pregnancy is, the more antibodies go from the pregnant woman to the child.In theory, that would give the child a higher chance of getting severe disease. But on the other hand, the child might be better able to cope with illness if it is just a little more mature. Because of the rarity of the condition, this was difficult for us to investigate, but thanks to data from the DIONYSUS study, we were able to make such comparisons. This showed that it is better to wait longer. We now maintain a gestational age of 37 to 38 weeks, if possible.”
Verweij: “A good example of what this study has yielded in concrete terms. In that respect, this study also acted as a mirror. Perhaps we were a little too much in our own bubble after all. We thought: we are doing well, because our results are very good. It is a great example of working together internationally and learning from each other, especially in rare diseases.”
Patience
Of the four years the study took, most of De Winter's time was spent on local, medical ethics approvals, collecting data and obtaining data sharing agreements, agreements in which parties give permission to use their data.
“In one case, it took 2.5 years to get access to an institution's data system.
So our patience was pretty much tested,” he says.
Privacy also played a big role.European privacy rules (GDPR) dictate when and how data may be shared with other centers. De Winter: “Moreover, every country and center had its own interpretation of the GDPR. That made it quite complicated. But I am proud that we succeeded. We showed that it is possible to make such a large multicenter study a success. Many people often want this and we just did it.” De Winter and LUMC researcher Nina Houben raised concerns about this in a publication in The Lancet Regional Health - Europe.7
- Publication in The Lancet Haematology (December 2024)
- Publication in JAMA Network Open (January 2025)
- Publication Ultrasound in Obstetrics & Gynecology (January 2025)
- Publication in American Journal of Obstetrics & Gynecology (March 2025)
- Learn more about AFRICARhE's mission on this LinkedIn page and in this video. Want to support this project? To do so, check out this page (below).
- Two joint PhD researchers have been started, Rafiki Mjema in Tanzania and Assefa Desalew in Ethiopia.
- Publication The Lancet Regional Health - Europe (February 2025)
