LUMC sheds new light on treatment of babies with rhesus disease with international database. RhD is the most common cause of anemia in unborn children. Although the condition is rare, there are several options for treating it. To understand the differences in care, LUMC initiated a global study. Together with 30 centers from 21 countries, the largest database of patients with rhesus disease was compiled.
The study provided a lot of new insights to improve care around this disease. 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. This can lead to severe anemia. This usually occurs after a previous pregnancy with a rhesus D-positive baby, when the mother has developed antibodies.
LUMC expertise
LUMC says it is a global expert on rhesus disease. The hospital also serves as a national fetal therapy referral center. This means that pregnant women from all over the country come to LUMC for treatments of the unborn child. Partly because of this, the LUMC has a good overview of all treatment options. LUMC has also published a lot 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 global study,” says LUMC researcher Derek de Winter.
Global study
In the DIONYSUS study, he examined what treatments against rhesus disease exist in the world and how they are applied. The study involved 31 centers from 22 countries. These were mainly countries 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.
The data that were collected can only be traced indirectly. In total, it provided data from about 2,400 pregnancies. About 4 percent of those pregnancies resulted in infant mortality. Two thirds of those died from rhesus disease, often as a result of so-called hydrops. That is the accumulation of fluid in different parts of the fetus' body. Or they died of severe anemia, usually because they were referred too late to a center of expertise.
Differences between centers
That information gathered showed that care around rhesus disease varies widely between countries and centers. De Winter says there were differences in almost all aspects of care. Based on the findings, several new international studies were launched to reduce the differences in treatment between centers, two of which were published recently.
Furthermore, the researchers 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 little to no data available from Africa and Southeast Asia. For this 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 investigate ways to prevent the disease there.
Gynecologist Joanne Verweij of the LUMC 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,” Verweij says. Yet according to her, the disease is simple to prevent with anti-D. Together with colleagues from Ethiopia, Tanzania and Malawi, they have set up studies to gain knowledge about the disease.
Extending gestational age
Another insight following the global study was about the length of gestational age at birth. De Winter explains that the standard was for a baby with severe rhesus disease to be born between 36 and 37 weeks. The idea being 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 De Winter and his colleagues to investigate on their own, but thanks to data from the DIONYSUS study, the comparison could be made. “This showed that it is better to wait longer. We now stick to a gestational age of 37 to 38 weeks, if possible,” De Winter explains.
Patience
Of the four years the study took, De Winter spent the most time on local, medical ethical 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,” De Winter adds.
Privacy also played a big role in the investigation. European privacy regulations (GDPR) dictate when and how data can be shared with other centers. What complicated this was that each country and center has its own interpretation of the GDPR. That made it quite complicated, according to De Winter. “But I'm proud that we succeeded. We showed that it is possible to make such a large multicenter study a success.” That LUMC is at the forefront of innovation is also evidenced by the newly opened center for surgery without cutting.
