It is reckoned that 1 in 25000 pregnancies are complicated by thrombotic microangiopathy (TMA). That is 40 in a million pregnancies. There are several causes of those TMAs. Pre- eclampsia being one of the most common reasons.
But aHUS is also a cause, an extremely rare cause, probably much less than 1 in 40 of those TMAs.
However when looked at within all the triggers of aHUS it is seen as much more common. Between 20% and 25% of female aHUS onsets are due to pregnancy. As a key trigger of aHUS the topic raises much comment within the aHUS community. The need for information about aHUS and pregnancy is embedded in the Global aHUS patient research agenda.
It is in someways almost a unique situation where someone is deciding to potentially make themselves ill with the disease before it happens. A transplant decision is the same.
So much of the discussion about it is about getting answers to the risks to the mother and the baby. As aHUS in pregnancy is most likely to occur after delivery, i. e. post partum, any information might be too late by then anyway.
Any information can only help those considering having a first child knowing the mother is predisposed (or having a second pregnancy following a previous on set by their first pregnancy , or aHUS unexpectedly triggering during pregnancy.
There is no doubt that these there is much more information available to help with such decision these days. Much more than there was even five years ago (and the issue of aHUS and pregnancy had been recognised for decades before that).
There are several facets to think about but one which has created the most uncertainty is the use of eculizumab during a pregnancy.
There was no data available from the early eculizumab trials for treating both PNH and aHUS because pregnant women were excluded from the trial. Those women who were included were expected to take precautions to avoid becoming pregnant whilst on the trial.
So data has had to collected post marketing authorisation.
PNH parents were in the vanguard in testing out the impact of eculizumab during pregnancy as well as the impact on the child. Some aHUS parents followed on even though nothing conclusive was said. Slowly anecdotal data from case studies began to emerge. Eculizumab appeared to be beneficial to treating aHUS mothers during pregnancy and as well as not adversely affecting the child.
A recent ‘safety report” on the use of eculizumab from 2009 to 2016 by both PNH and aHUS mothers concluded that there were no safety issues.
That did not mean that all eculizumab pregnancies resulted in successful live births. There were still births and miscarriages but fewer of those happened to aHUS parents and not because of eculizumab.
The most significant data was how many parents elected to terminate the pregnancy and how much more likely it was that aHUS parents would chose to do so than PNH parents. Four times as likely. One in four aHUS pregnancies was terminated by parents.
Another set of data has been published recently. It comes from a research group using data from the aHUS Registry. So there is some overlap with other study’s patients, but offering more recent data. A copy of the abstract about it presented a haematology conference in Australia a few months back can be seen here.
This study produced similar findings, but, even though it included more recent cases of aHUS pregnancy, the study reported that 1 in 3 aHUS pregnancies resulted in elected termination when the mother was receiving eculizumab. By contrast only one of the mothers pregnant whilst not on eculizumab elected to terminate.
The researchers offered little or no explanation on these revelations. Why does the behaviour of parents differ between the two diseases whilst using the same drug. And also why are those with aHUS on eculizumab generally acted differently from those who were not. Although in most eculizumab treated patients a concern was reported for the health of the mother.
So why is this happening, and is it still happening, that aHUS pregnancies are being terminated at significantly high rate! It is not entirely clear whether eculizumab was rescue therapy or was routine a treatment at the time of conception. Could it be more to do with the nature of aHUS or its diagnostic difficulty rather than what harm eculizumab might do?
To answer that more knowledge is needed on the circumstances, timelines, available information given and the perspective of the parents at the time the decision was made.
This is not about a right to chose, parents must make the choice.
In the past the conventional advice would be to abort. No one is yet saying definitely go ahead.
It is about whether data can aid the right choice in a very difficult situation for them.