Phenylalanine and tyrosine measurements across gestation by tandem mass spectrometer on dried blood spot cards from normal pregnant women

Abstract

Purpose: Maternal phenylketonuria (MPKU) requires strict control of phenylalanine (Phe) and supplemental tyrosine (Tyr). Monitoring during pregnancy using dried blood spot (DBS) cards by tandem mass spectrometry (MS/MS) is now standard practice, however there are no Phe and Tyr reference ranges for DBS MS/MS method in healthy pregnant women. Methods: DBS cards (63–1364 days in storage) from healthy women with singleton pregnancies were analyzed by MS/MS. Three hundred ninety DBS cards from 170 pregnancies (5/1–39/6 weeks’ gestation), were tested. Results: Both Phe and Tyr levels declined from the first trimester (Phe: 36.2 +/− 10.6; Tyr 25.7 +/− 9.7 µmol/L) to the second trimester (Phe 33.4+/−9.3; Tyr 21.7+/− 6.7 µmol/L) and remained stable in the third trimester (Phe 32.3 +/− 8.7; Tyr 21.0 +/− 6.6 µmol/L). Phe and Tyr levels declined over time since collection (Phe: 0.004 µmol/L per day; Tyr 0.002 µmol/L). Nomograms by gestational age were created using raw data and data adjusted for time from sample collection. Reference ranges by trimester are provided. Conclusions: Both Phe and Tyr decline quickly during the first trimester and remain relatively constant over the second and third trimesters. These nomograms will provide a valuable resource for care of MPKU.