Congenital cardiac malformations in offspring of mothers with phenylketonuria and hyperphenylalaninemia

M. E M Pierpont, L. J. Sletten, C. F. Smith, H. Berry, S. A. Berry, R. O. Fisch

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Previous reports have suggested that offspring of mothers with phenylketonuria (PKU) or hyperphenylalaninemia (HPA) are at higher risk for congenital cardiac malformations (CCM). In this review, we discuss four infants born to mothers with PKU, two with confirmed CCM. In addition, all available literature reports from 1961-1993 were reviewed as to the pregnancy outcome and presence of CCM. Of 452 pregnancies in 172 women (including families reported here for the first time) with PKU, there were 397 liveborn infants, 55 miscarriages or stillbirths, and four elective abortions. Of liveborn infants, 31 of 397 (7.8%) had documented CCM; a further 6.3% were suspected of having CCM because of cyanosis or murmurs. Complex cardiac disease or multiple cardiac malformations - including nine infants with hypoplastic left heart syndrome, one with transposition of the great vessels, five with tetralogy of Fallot and eight infants with more than one CCM-occurred in 23 of 31 children with documented CCM. Single cardiac malformations such as ventricular septal defect, patent ductus arteriosus or pulmonary stenosis occurred in eight of 31 children. When the first trimester maternal blood phenylalanine concentration (MBPC) was less than 600 μmol/L, none of the offspring had CCM. For a first trimester MBPC from 601-900 μmol/L, there were four children with suspected or confirmed CCM. A first trimester MBPC greater than 901 μmol/L was associated with suspected or confirmed CCM in 50 of 303 exposed pregnancies. This study indicates that maternal PKU is associated with a much higher risk of CCM than exists in the general population. Particularly, the occurrence of hypoplastic left heart syndrome in 2.3% of the liveborn infants of this study group is considerably higher than the 0.008% expected for the general population.

Original languageEnglish (US)
Pages (from-to)242-249
Number of pages8
JournalInternational Pediatrics
Issue number3
StatePublished - 1995


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