Dietary management in pregnant Phenylketonuria (PKU) patients: comparison with protein and phenylalanine requirements in healthy pregnancies

Background: Diet, with an emphasis on phenylalanine restriction, is recognized as an effective treatment for phenylketonuria (PKU). A similar approach is used in pregnant PKU patients to reduce teratogenic effects of elevated circulating phenylalanine. Our objective was to assess the dietary management of pregnant PKU individuals at Vancouver General Hospital, Canada, retrospectively including dietary recommendations, phenylalanine intake, patient compliance and a comparison with protein and phenylalanine requirements determined in healthy pregnancies. Methods: We reviewed dietitian’s health records for pregnant patients monitored for PKU between 1999-2019 at the Adult Metabolic Diseases Clinic (AMDC). Data were extracted on demographics, gestational weight gain, gestational age at delivery, pregnancy outcomes, plasma analyses, reported health concerns, and dietary intake of phenylalanine, tyrosine, and protein. We present descriptive statistics of subject characteristics and clinical results. Paired sample t-test assessed for differences between prescribed phenylalanine and phenylalanine intake. Generalized additive mixed models approach was used to observe changes in phenylalanine concentration in blood spots and phenylalanine tolerance throughout the pregnancy. Results: Eleven patients aged 20-40 years, with a total of 16 pregnancies, were included for analysis. Prescribed phenylalanine intake increased from 7.2 ± 4.3 to 16.7 ± 4.8 mg·kg-1·d-1 between early (13-19wk) and late (33-39wk) gestation. Actual phenylalanine intakes increased from 7.5.2 ± 4.3 to 17.7 ± 4.9 mg·kg-1·d-1 between these stages and were not statistically different. When compared to our previously determined mean phenylalanine requirements in healthy pregnancies during ~16wk pregnancy (15 mg·kg-1·d-1) and late (~36wk) pregnancy (21 mg·kg-1·d-1), phenylalanine intake was 50% lower at 13-19wk gestation and 16 % lower at 33-39wk gestation. Mean phenylalanine concentration in blood spots decreased as pregnancy progressed, with the mean concentration being highest preconception, and a slight increase between 8 and 12 wk. Conclusions: Current management practices at AMDC are working well to achieve targeted metabolic control. Increase in phenylalanine requirements during early healthy pregnancy, combined with slight increase in blood spot phenylalanine in early PKU pregnancy is intriguing and suggests a need to directly determine phenylalanne needs. This natural history analysis provides reference values and management practices of pregnant PKU patients, contributing to the limited data available.