Preface

Abstract

The story of the maternal phenylketonuria (PKU) syndrome has been fascinating to those of us involved in the earliest descriptions of pregnancy outcome in women with PKU. During the years preceding the discovery by Horst Bickel of the benefits of the phenylalanine-restricted diet, PKU was such a destructive disorder that few women with PKU were able to conceive and carry a pregnancy to term. It was not until the middle of the 20th century that the first descriptions of pregnancy outcome in women with PKU were published.The Lenke and Levy international survey published in 1980 documented a very high frequency of birth defects in offspring of women with PKU. These included a 92% frequency of mental retardation, 73% microcephaly, 40% low birth weight, and 12% congenital heart disease. Similar, although less severe, results were noted in offspring of women with hyperphenylalaninemia, a milder form of the disorder. This led Kirkman to suggest that mental retardation in the offspring would soon erase the advantages gained by newborn screening in virtually eliminating mental retardation from PKU unless some remedy for the problem were found. This remedy could be treatment with a phenylalanine-restricted diet during pregnancy, which had been reported to reduce fetal damage from maternal PKU and in some instances could prevent the damage, particularly if begun before conception, with good control of their blood phenylalanine levels. However, the optimal conditions for this treatment had to be established.The paucity of the information about the treatment of maternal PKU stimulated the National Institute of Child Health and Human Development (NICHD), National Institutes of Health, to embark on the Maternal PKU Collaborative Study. The Study was designed as a prospective, longitudinal, and observational project that included a uniform research protocol and participation by 102 clinics throughout the United States in identifying, tracking, and enrolling women with PKU/hyperphenylalaninemia. In 1985, 11 clinics in Canada joined the study under the coordination of the Hospital for Sick Children, and 14 clinics in Germany, Switzerland, and Austria joined the study in 1992. The contributions of all of the participating clinics deserve praise for their willingness to diligently collect data on behalf of the study.The Maternal PKU Collaborative Study had its beginnings in 1984 and concluded in 2002. Fortunately, the principal investigators were individuals with many years of personal experience with PKU and were able to work together in amassing the data presented in this report. To accomplish the goals of the study, stable funding from NICHD and Canada’s National Health Research and Development Program made the study possible.The Data Coordinating Center, located at Children’s Hospital Los Angeles, processed, validated, analyzed, and stored all collected data and then prepared reports for the Study and NICHD.To all consultants and participants, we express the gratitude due them. Alfred Baumeister, Janina Galler, and Edward McCabe were particularly helpful.