Pregnancy and aHUS
Pregnancy is a well-recognised trigger of primary complement mediated aHUS. It is a trigger in ~20% of females who develop aHUS. The onset of aHUS is usually in the final trimester or in the post-partum period. Over half of first presentations of aHUS that occur during pregnancy or post-partum associate with a first pregnancy, with most of the other presentations during a second pregnancy. Genetic abnormalities in the complement system have been identified in over 50% of cases. In the Pre-Eculizumab era half of patients had progressed to end-stage renal failure by 7 years.
Studies of eculizumab in aHUS and pregnancy are very limited. The use of eculizumab may need to be considered in the following clinical scenarios – all should be discussed with the National aHUS service and recommendations will be made on a case by case basis.
- Patients with known aHUS and currently receiving eculizumab
- Patients with known aHUS and currently not receiving eculizumab
- De-novo cases of aHUS associated with pregnancy
- Patients with carrier status following genetic screening
Monitoring Eculizumab Therapy during pregnancy
From the limited experience of Eculizumab treatment during pregnancy for complement mediated aHUS it appears that there is an increasing requirement for Eculizumab as the pregnancy progresses. We recommend ensuring adequate blockade using CH100/AH100 (or CH50/AH50) at booking with increased frequency of monitoring from the second trimester onwards. Eculizumab dosage alteration should be undertaken in collaboration with the National aHUS centre
Risks of Eculizumab during pregnancy
There is no evidence that eculizumab use has caused harm to the new-born, though most of the data is observational, from eculizumab use in patients with paroxysmal nocturnal haemoglobinuria (PNH). The largest reported experience of eculizumab use during and after pregnancy was in 75 pregnancies in 61 women. Twenty cord-blood samples were examined for the presence of eculizumab; the drug was detected in 7 of the samples. In another study in which eculizumab was detected in cord blood, there was normal complement activity in 2 new-borns suggesting that even if eculizumab crosses the placenta, the level is not high enough to affect complement activation.
In the PNH study, a total of 25 babies were breast-fed, and in 10 of these cases, breast milk was examined for the presence of eculizumab; the drug was not detected in any of the 10 breast-milk samples. These findings suggested that the drug is not excreted into breast milk in measurable amounts and that breast-feeding by patients receiving eculizumab is likely to be safe.