One of my patient’s on the dialysis service is a pregnant woman on chronic maintenance dialysis. The question that I asked the renal fellow: what is the optimal hemoglobin (Hb)in a pregnant patient? And, second, is exposure to epoetin-alfa safe for the fetus?
The almost instantaneous answer back from the fellow – and yes we have really smart fellows – was: “I’ve looked this up – there are very few studies – but the best data we have suggests is a HB of 9 to 11 g/dL” And “yes, it’s OK to give Epogen during pregnancy”. The fellow was correct.
So what’s the evidence?
The best evidence comes from observational studies. One study stands out: the study by Mark P. Little from Imperial College in London published in 2005 (American Journal of Obstetrics and Gynecology (2005) 193, 220–6).
They performed a prospective cohort study using data on 222,614 first singleton pregnancies in the St Mary’s Maternity Information System database in the Northwest Thames region of London. They reported that the lowest perinatal mortality was associated with a lowest recorded maternal hemoglobin concentration of between 9-11 g/dL (see Figure). Too high a Hb is associated with increased perinatal mortality rates, early neonatal mortality, as well as stillbirths. Too low a Hb is associated with preterm birth and fetal growth restriction.
What about the safety of Epogen to the fetus? The U.S. FDA classifies Epogen as a “Pregnancy Category C” drug. Pregnancy Category C is given to medicines that have not been studied in pregnant humans but that do appear to cause harm to the fetus in animal studies. Also, medicines that have not been studied in any pregnant women or animals are automatically given a pregnancy Category C rating. Epogen was given a pregnancy Category C classification because it caused problems in animal studies. Giving the drug to pregnant rats increased the risk of low birth weight, delayed development, and missing vertebrae (spinal bones). However, there is no evidence that Epogen has the same effects on human fetus’s. Therefore, a pregnancy Category C medicine, such as Epogen, may be given to a pregnant woman if the healthcare provider believes that the benefits to the woman outweigh any possible risks to the unborn child. Some have suggested that pregnancy is associated with a higher ESA dose requirement, but the data is quite limited (Maruyama H et al, Nephron 1998). And, like Epogen, darbepoetin or Aranesp and peginesatide are pregnancy category C drugs. A similar warning is in place for Mircera.
However, the Epogen label recommends that pregnant women should not be treated with Epogen from multi-dose vials because the Epogen in these vials contains benzyl alcohol. Benzyl alcohol has been shown to cause brain damage, other serious side effects, and death in newborn and premature babies. Epogen that comes in single-dose vials does not contain benzyl alcohol.
Bottom-line: for the pregnant dialysis patient, aim for a Hb of 9 to 11 g/dL and use the lowest possible dose of ESA.