Men who receive blood transfusions from women with a history of pregnancy are 13% more at risk of dying early – known as a “mother effect” – according to a new research published in the Journal of American Medical Association (JAMA).

The study, conducted by researchers from the Leiden University Medical Centre in the Netherlands, observed over a median of 245 days, 31,118 individuals between the ages of 42 and 77 – who received blood transfusions in the Netherlands, between the years 2005 to 2015. A total of 88% of the donors were male, 6% were women who had been pregnant and 6% were women who had not been. This is because men can donate blood more often than women. Women with an unknown pregnancy history were exempted from the study.

Study to provide significant clinical implications – IF true

The results of the study:

In total, 3,969 patients died during the study. The risk of dying was the approximately the same after blood transfusions from a man (80 deaths per 1,000) or a never-pregnant woman (78 deaths per 1,000). However, men who received blood from women with a history of pregnancy, witnessed 101 deaths per 1000 people per year.

This meant that for a man who received blood from a woman who had been pregnant, his chances of dying within that year were raised by 13% for every unit of blood he received. As for women, there was no statistical difference in the rate of death between those who received blood from any category of donors.

The findings "are provocative and may — if true — have significant clinical implications," for both the acceptance of blood donations and the process of blood transfusions, Dr Ritchard Cable, of the American Red Cross Blood Services, wrote in an editorial for the study. However, many have debunked the study for its poor methodology.

Experts argue study fails to prove statistical significance

To begin with, researchers only included individuals who had received transfusions in one of three cases. Either they had received blood from male donors, or from female donors who had never been pregnant, or from female donors who had a history of pregnancy. This means that patients who had received transfusions from both male and female donors with a history of pregnancy for example, were not included.

Since the patients in the study only received transfusions from one type of donor, they received fewer transfusions than the average transfusion patient does. Therefore, it was not reflective of the real-world situation.

Furthermore, the increased risk of death in men who had received transfusions from pregnant women was only seen in men aged 50 and younger. Additionally, the researchers tested a number of different pairings such as male and female recipients in four different age groups, male and female donors at different stages of pregnancy, men and women who got a single transfusion or many. Yet, they failed to account for statistical associations that may occur randomly which begs the question of whether the analysis was valid or not.

All of these factors meant that according to Cable, it was “a very complex study design” that a lot of the reviewers and JAMA editors “had trouble with.”

“It’s not at all clear,” he remarked.

Explanation required to justify increased number of deaths

Whilst death from transfusions are now rare, the most common cause of transfusion-related deaths is transfusion-related acute lung injury or (TRALI). The researchers believe that changes that occur to a pregnant woman’s immune system could be the trigger for the deaths.

The researchers speculated in the paper, that antibodies or other immune factors that develop during pregnancy could cause TRALI in male recipients. Some of the antibodies produced are made for molecules produced by genes on the Y chromosome, if the child the woman has is male.

This appears to be more likely to occur if the transfusion contained more plasma than red blood cells. However, this poses the question, according to Rutger Middelburg, an epidemiologist at Leiden University Medical Center of whether there are enough such lymphocytes to trigger a lethal immune reaction.

For now, the researchers do not even know exactly what the patients died of or “why the [mortality] effect should be limited to … men under 50,” said Middelburg.

“An alternative explanation could be a difference in iron status between ever-pregnant female and male donors. Some studies also report differences in red blood cell physiology between the sexes,” Middelburg wrote in the report.

For now, the authors have said, “further research is needed to replicate these findings, determine their clinical significance, and identify the underlying mechanism.” They say all women, including those pregnant should continue to donate blood. MIMS

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