European Journal of Pediatrics

, Volume 178, Issue 7, pp 1005–1011 | Cite as

Maternal phenylketonuria in Turkey: outcomes of 71 pregnancies and issues in management

  • Yılmaz YıldızEmail author
  • Hatice Serap Sivri
Original Article


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).

Conclusion: More frequent phenylalanine measurements during late first trimester are crucial to improve outcomes in treated pregnancies. In order to prevent untreated pregnancies via detecting undiagnosed adults, countries where significantly many women of childbearing age were not screened as newborns may consider pre-pregnancy PKU screening. Microcephaly in the newborn should prompt screening for PKU in the mother.

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.


Phenylketonuria Phenylalanine hydroxylase deficiency Hyperphenylalaninemia Maternal phenylketonuria Pregnancy 





Intellectual disability or developmental delay


Intelligence quotient


Interquartile range


Intrauterine growth restriction


Last menstrual period


Newborn screening


Phenylalanine hydroxylase







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.

Authors’ contributions

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.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

431_2019_3387_MOESM1_ESM.pdf (527 kb)
Online Resource 1 Detailed Characteristics of Children Born to Mothers with Phenylalanine Hydroxylase Deficiency. (PDF 527 kb)
431_2019_3387_MOESM2_ESM.pdf (182 kb)
Online Resource 2 Medians and interquartile ranges of blood Phe levels and weekly frequencies of Phe measurements in classical PKU pregnancies treated with Phe-restricted diet. (PDF 181 kb)
431_2019_3387_MOESM3_ESM.pdf (107 kb)
Online Resource 3 Blood Phe Measurements in Classical PKU Pregnancies Treated with Phe-Restricted Diet. Weeks 14 and 28 mark the start of second and third trimesters, respectively. Week 6 divides the first trimester into two parts. “0” marks the last menstrual period. The accepted upper limit of blood Phe level during pregnancy is 6 mg/dl. Blood Phe levels are higher and fluctuate more in especially the second part of the first trimester, after which Phe levels drop and remain stable for the most part. Phe: phenylalanine, PKU: phenylketonuria. (PDF 106 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Pediatric Metabolism, Department of Pediatrics, Faculty of MedicineHacettepe UniversityAnkaraTurkey

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