New England Maternal PKU Project: Prospective study of untreated and treated pregnancies and their outcomes Four women with classic phenylketonuria (blood phenylalanine >t200 t~mol/L) were given a phenylalanine-restricted diet; three also received L-tyrosine supplements. Biochemical measures of nutrition were normal except for iron deficiency anemia, and in one woman folate deficiency. One pregnancy in which treatment began before conception and another treated from 8 weeks gestation, both with blood phenylalanine levels maintained at t20 to 730 ~mol/L, resulted in normal newborn infants whose postnatal growth and development have also been normal. A third pregnancy, treated from 6 gestational weeks, was marked by poor dietary compliance until the middle of the second trimester; fetal microcephaly was identified by ultrasonography at 28 weeks but not at 21 weeks. The child has microcephaly and motor delay. The fourth pregnancy, not treated until the third trimester, produced a child with microcephaly, mental retardation, hyperactivity, and neurologic deficits. It is likely that fetal damage from maternal phenylketonuria can be largely and perhaps entirely prevented by dietary therpay, but therapy must begin before conception for the best chance of a normal infant. (J PEDIATR 1987;110:391-8) Frances J. Rohr, M.S., R.D., Lauren B. Doherty, R.N., M.S., Susan E. Waisbren, Ph.D., Isabel V. Bailey, M.S.W., Mary G. Ampola, M.D., Beryl Benacerraf, M.D., and Harvey L. Levy, M.D. From the NEM-PKUProgram, The Children's Hospital, Joseph P. Kennedy Laboratories of the Neurology Service, Massachusetts General Hospital, and the Departments of Neurology, Pediatrics, and Obstetrics and Gynecology, Harvard Medical School, and the Department of Pediatrics and the Pediatric Amino Acid Laboratory, Tufts-New England Medical Center, Boston Women with phenylketonuria are at risk for bearing children with birth defects, including mental retardation, microcephaly, congenital heart disease, and low birth weight. ~ These complications affect infants both with and without PKU, and do not occur when the father but not the Supported by a Maternal and Child Health Research Grant (Social Security Act, Title V; MCJ 250501) from the Bureau of Health Care Delivery and Assistance, Health Resources and Services Administration, and by Grant NS 05096 from the National Institute of Neurological and Communicative Disorders and Stroke. Submitted for publication March 3, 1986; accepted Oct. 10, 1986. Reprint requests: Frances J. Rohr, M.S., R.D., Gardner 650, The Children's Hospital, 300 Longwood Ave., Boston, MA 02115. mother has PKU. 2 Thus they are a consequence of mater- nal PKU, presumably mediated by biochemical perturba- tions that traverse the placenta and damage the fetus. Treatment with a phenylalanine-restricted diet during pregnancy, particularly if initiated before conception, seems to offer some protection to the fetus? '4 However, the PKU Phenylketonuria [ extent to which the fetus is protected is unknown. Largely unanswered also are questions such as the frequency of pregnancy interruption, safety of the special diet, the value of ultrasonography in assessing fetal complications, and the needs of these families for support after birth of the infant. 391