Maternal Phenylketonuria and Offspring Outcome: A Retrospective Study with a Systematic Review of the Literature

Background: Phenylketonuria (PKU) poses significant challenges for maternal and neonatal outcomes, requiring strict adherence to dietary protocols to maintain optimal maternal phenylalanine (Phe) levels during pregnancy. This study retrospectively analyzed outcomes of pregnancies in PKU-affected women and conducted a systematic review on the timing of dietary management and its impact on outcomes. Methods: This retrospective study included data from nine PKU-affected women and 14 pregnancies followed at the Regional Reference Center for Metabolic Diseases in Catania. Women were categorized based on the timing of dietary intervention: preconception (pcD), during pregnancy (pD), or never (nD). Maternal Phe levels were classified as in-target (tP+) or non-target (tP-). A systematic review of the literature was conducted using PRISMA methodology, including 77 studies reporting maternal Phe levels, dietary timing, and clinical/auxological offspring outcomes. Results: In the retrospective study, pcD and tP+ groups had significantly better neonatal outcomes, with lower rates of congenital heart disease (CHD), facial dysmorphisms, intrauterine growth restriction (IUGR), and microcephaly. Systematic review data from 1068 PKU-affected women and 2094 pregnancies revealed that pcD with tP+ resulted in the lowest rates of miscarriage (0.14%) and adverse neonatal outcomes, while tP- and nD groups showed the highest rates of CHD, microcephaly, and intellectual disability. Conclusions: Early dietary intervention, ideally preconceptionally, and achieving target maternal Phe levels are critical in reducing adverse outcomes in pregnancies of PKU-affected women. These findings emphasize the importance of metabolic control and adherence to dietary protocols in maternal PKU management.