Phenylketonuria (PKU) is an inherited condition involving the inability to metabolize phenylalanine, an essential amino acid. Until recently, treatment to control serum levels of phenylalanine18 had been targeted mainly to infants and children: if treatment with a phenylalanine-restricted diet is initiated early in infancy, it helps prevent abnormal brain development and severe mental retardation while allowing normal growth. This rather complicated diet (which requires the use of expensive, specially formulated low-phenylalanine products) is usually discontinued in adulthood, when elevated serum levels of phenylalanine have been presumed to be no longer neurotoxic.
If pregnancy occurs, however, excessive amounts of phenylalanine in the maternal serum are associated with an extremely high incidence of mental retardation, microcephaly, low birth weight, and congenital heart disease among infants who themselves have not inherited PKU. 19–21 There is evidence that the occurrence of these problems can be reduced (although not perhaps eliminated) if the mother maintains a low serum phenylalanine level before conception and throughout pregnancy.21–24
To achieve and maintain the desired phenylalanine level, the mother should be identified before pregnancy25 and helped to modify her intake.26 For this purpose, she will need intensive support and follow-up by an interdisciplinary team, including a dietitian experienced in the treatment of this disorder. If the mother's intellectual abilities are limited (perhaps because of inadequate dietary control of her condition during her early years), simplified strategies for diet modification and skillful teaching will be needed.27
Two adverse outcomes of a previous pregnancy—neural tube defects (such as spina bifida) and fetal alcohol syndrome—should alert the health care provider to the need for attention to preventive measures before pregnancy.
Once a woman has delivered an infant with a neural tube defect, her risk of delivering another affected infant (often called a recurrent neural tube defect) is very high—2 to 10%.10. The results of a recent randomized clinical trial in Great Britain28 indicated that high-dose (4-mg/day) folic acid supplements given before conception and throughout the first trimester were protective against recurrent neural tube defects. (The critical