Maternal phenylketonuria in Turkey: outcomes of 71 pregnancies and issues in management
Untreated phenylketonuria (PKU) in pregnancy causes a severe embryopathy called maternal PKU syndrome. Here, we aimed to assess management issues and pregnancy outcomes in the first published series of PKU pregnancies from the developing world. Data were collected retrospectively in a single center from 71 pregnancies and 45 live births of 32 women with PKU, 11 of whom were diagnosed in adulthood after having an affected child. Microcephaly, intellectual disability, and dysmorphic facies were more prevalent in offspring of untreated than treated pregnancies with classical PKU (100% vs. 0%, 91% vs. 0%, and 73% vs. 23% with p < 0.001, p < 0.001, and p = 0.037, respectively). In treated pregnancies, phenylalanine levels were higher during weeks 6–14 than other periods of gestation (4.38 vs. 3.93, 2.00 and 2.28 mg/dl; p < 0.05). Poor compliance correlated with higher phenylalanine levels (ρ = − 0.64, p = 0.019) and fluctuations (ρ = − 0.66, p = 0.014).
What Is Known
•Untreated phenylketonuria during pregnancy causes maternal phenylketonuria syndrome in the newborn.
•Effective treatment throughout pregnancy can prevent adverse fetal outcomes.
What Is New:
•Metabolic control is related to frequency of follow-up and worsens during late first trimester. Closer follow-up during this period may improve metabolic control.
•In order to prevent untreated pregnancies, pre-pregnancy phenylketonuria screening may be considered if many women of childbearing age were not screened as newborns.
KeywordsPhenylketonuria Phenylalanine hydroxylase deficiency Hyperphenylalaninemia Maternal phenylketonuria Pregnancy
Intellectual disability or developmental delay
Intrauterine growth restriction
Last menstrual period
The authors would like to acknowledge İmran Özalp for establishing the first metabolic center and newborn screening in Turkey; metabolic physicians Turgay Coşkun, Ayşegül Tokatlı, Ali Dursun, Halil İbrahim Aydın, Mustafa Kılıç, Özlem Ünal, Burcu Öztürk Hişmi, Berrak Bilginer Gürbüz, and Emine Pektaş; metabolic dietitians Gülden Köksal, Hülya Gökmen-Özel, Sabriye Saruhan, and others for the diagnosis and management of the patients in this paper; Talat Demirsöz, Gökçen Düzgün Konuşkan, Yamaç Karaboncuk, Zeynep Tüzün, Berge Velibaşoğlu, and Tuğba Kaya for performing neuropsychometric testing; Esin Göksun and Rıza Köksal Özgül for the genetic analyses; Özgür Özyüncü for providing obstetric care; our laboratory staff; and our patients and their families. This work was prepared as a residency thesis in pediatrics.
The study was conceptualized by HSS. Both authors (YY and HSS) contributed to study design and interpretation of data. YY was involved in acquisition and analysis data and writing the draft of the manuscript, which was critically edited by HSS. Both authors approved the final version.
Compliance with ethical statements
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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