Abstract
For pregnant women with phenylketonuria (PKU), maintaining blood phenylalanine (Phe)<360μmol l is critical due to the toxicity of elevated phe to the fetus. sapropterin dihydrochloride (sapropterin) lowers blood phe in tetrahydrobiopterin (bh4) responsive patients with pku, in conjunction with a phe-restricted diet, but clinical evidence supporting its use during pregnancy is limited. as of june 3, 2013, the maternal phenylketonuria observational program (pku moms) sub-registry contained data from 21 pregnancies - in women with pku who were treated with sapropterin either before (n="5)" or during (n="16)" pregnancy. excluding data for spontaneous abortions (n="4)," the data show that the mean of median blood phe [204.7±126.6μmol l (n="14)]" for women exposed to sapropterin during pregnancy was 23% lower, and had a 58% smaller standard deviation, compared to blood phe [267.4±300.7μmol l (n="3)]" for women exposed to sapropterin prior to pregnancy. women on sapropterin during pregnancy experienced fewer blood phe values above the recommended 360μmol l threshold. when median blood phe concentration was><360μmol l throughout pregnancy, 75% (12 16) of pregnancy outcomes were normal compared to 40% (2 5) when median blood phe was>360μmol/L. Severe adverse events identified by the investigators as possibly related to sapropterin use were premature labor (N=1) and spontaneous abortion (N=1) for the women and hypophagia for the offspring [premature birth (35w4d), N=1]. One congenital malformation (cleft palate) of unknown etiology was reported as unrelated to sapropterin. Although there is limited information regarding the use of sapropterin during pregnancy, these sub-registry data show that sapropterin was generally well-tolerated and its use during pregnancy was associated with lower mean blood Phe. Because the teratogenicity of elevated maternal blood Phe is without question, sapropterin should be considered as a treatment option in pregnant women with PKU who cannot achieve recommended ranges of blood Phe with dietary therapy alone. For pregnant women with phenylketonuria (PKU), maintaining blood phenylalanine (Phe)<360μmol l is critical due to the toxicity of elevated phe to the fetus. sapropterin dihydrochloride (sapropterin) lowers blood phe in tetrahydrobiopterin (bh4) responsive patients with pku, in conjunction with a phe-restricted diet, but clinical evidence supporting its use during pregnancy is limited. as of june 3, 2013, the maternal phenylketonuria observational program (pku moms) sub-registry contained data from 21 pregnancies - in women with pku who were treated with sapropterin either before (n="5)" or during (n="16)" pregnancy. excluding data for spontaneous abortions (n="4)," the data show that the mean of median blood phe [204.7±126.6μmol l (n="14)]" for women exposed to sapropterin during pregnancy was 23% lower, and had a 58% smaller standard deviation, compared to blood phe [267.4±300.7μmol l (n="3)]" for women exposed to sapropterin prior to pregnancy. women on sapropterin during pregnancy experienced fewer blood phe values above the recommended 360μmol l threshold. when median blood phe concentration was><360μmol l throughout pregnancy, 75% (12 16) of pregnancy outcomes were normal compared to 40% (2 5) when median blood phe was>360μmol/L. Severe adverse events identified by the investigators as possibly related to sapropterin use were premature labor (N=1) and spontaneous abortion (N=1) for the women and hypophagia for the offspring [premature birth (35w4d), N=1]. One congenital malformation (cleft palate) of unknown etiology was reported as unrelated to sapropterin. Although there is limited information regarding the use of sapropterin during pregnancy, these sub-registry data show that sapropterin was generally well-tolerated and its use during pregnancy was associated with lower mean blood Phe. Because the teratogenicity of elevated maternal blood Phe is without question, sapropterin should be considered as a treatment option in pregnant women with PKU who cannot achieve recommended ranges of blood Phe with dietary therapy alone.
