Background: Untreated maternal phenylketonuria or hyperphenylalaninemia may result in nonphenylketonuric offspring with neonatal sequelae, especially intellectual disability, microcephaly, and congenital heart disease (CHD). Dietary treatment to control phenylalanine concentrations can prevent these sequelae. Objective: We aimed to present an overview of reported pregnancy complications and neonatal sequelae of maternal phenylketonuria or hyperphenylalaninemia in untreated and treated pregnancies. Design: A MEDLINE and EMBASE search was conducted for case reports and case series that assessed maternal phenylketonuria or hyperphenylalaninemia during pregnancy. Pregnancy complications (spontaneous abortion, intrauterine-fetal-death, and preterm delivery) and neonatal sequelae [small for gestational age (SGA), microcephaly, CHD, intellectual or developmental disabilities (IDDs), and facial dysmorphism (FD)] were analyzed. Fifteen unpublished pregnancies from our clinic were added. Results: We retrieved 196 pregnancies, of which 126 pregnancies were untreated and 70 pregnancies were treated. The occurrence of pregnancy complications was not significantly different between untreated and treated pregnancies. Except for SGA, all neonatal sequelae were more frequent in untreated pregnancies. Moreover, the occurrence of SGA, microcephaly, and IDDs was significantly related to the mean phenylalanine concentration in each trimester, whereas the occurrence of FD was related only to the first trimester. Conclusions: We present the largest cohort of untreated pregnant women with phenylketonuria or hyperphenylalaninemia since 1980. The results follow the general pattern reported by other researchers. We underline that the treatment of pregnant women with phenylketonuria or hyperphenylalaninemia is of great importance to prevent neonatal sequelae. We strongly recommend starting treatment before conception because we showed the deleterious effect of an increased mean first-trimester phenylalanine concentration on FD.

Embase, Medline, article, face dysmorphia, female, fetus death, first trimester pregnancy, human, hyperphenylalaninemia, intellectual impairment, ischemic heart disease, major clinical study, microcephaly, newborn assessment, phenylketonuria, pregnancy, pregnancy complication, premature labor, small for date infant, spontaneous abortion
dx.doi.org/10.3945/ajcn.110.009456, hdl.handle.net/1765/38297
The American Journal of Clinical Nutrition
Erasmus MC: University Medical Center Rotterdam

Prick, B.W, Hop, W.C.J, & Duvekot, J.J. (2012). Maternal phenylketonuria and hyperphenylalaninemia in pregnancy: Pregnancy complications and neonatal sequelae in untreated and treated pregnancies. The American Journal of Clinical Nutrition, 95(2), 374–382. doi:10.3945/ajcn.110.009456