JoGN N PR~UCIPLES & PRACTICE

Transcription

1 JoGN N PR~UCIPLES & PRACTICE Maternal Phenylketonuria: A New Cause for Concern Robin B. Kirby, RNC, MSN, CRNP = The start of newborn screening for phenylketonuria (PKU) during the early 1970s has given rise to an increasing number of women who have been identified and successfully treated for the disease in childhood and are now preparing to have children of their own. Early detection and initiation of nutritional therapy before conception is key to a successful pregnancy outcome. Nurses who understand the pathophysiology, dietary limitations, and management of PKU in pregnancy can provide the care necessary for optimal maternal and neonatal health. JOGNN, 28, ; Accepted: October, 1998 Nurses who work in maternal-child health are familiar with phenylketonuria (PKU). Newborns are screened for this disease every day, and nurses educate parents about the indications for testing and the risks associated with a positive result. Standard laboratory tests for PKU seldom, if ever, come back positive; therefore, health care providers tend to give little thought to the disease until they encounter a woman whose only apparent risk factor in pregnancy is that she has PKU. How should the pregnancy be managed, what are the risks to the fetus and neonate, and what areas of patient education need to be addressed, are questions that must be explored to provide for a positive pregnancy outcome. Since the beginning of newborn screening in the early 1970s, many women with PKU, who were successfully treated with phenylalaninerestricted diets in early childhood, are now reaching childbearing age and preparing to have children of their own (Imarmura et al., 1993). It is likely that nurses will see an increase in the num- ber of women with PKU desiring pregnancy or giving birth to a neonate with the disease. It is important, therefore, that health care providers have an understanding of PKU. What is Phenylketonuria? Phenylketonuria is an autosomal, recessively inherited, inborn error of metabolism. The disease is a result of an enzyme deficiency that prohibits phenylalanine, an essential amino acid found in most foods, from being synthesized and converted to tyrosine, another amino acid. Left untreated, the lack of enzyme activity causes phenylalanine levels to rise in the bloodstream. Excessive levels interfere with normal brain development, resulting in severe and irreversible mental retardation (Gibbings, 1994). The disorder is inherited when both parents are heterozygous carriers of the PKU gene. Both the mother and father carry one normal and one abnormal gene for the disease. Offspring in each pregnancy will have a 1:4 chance of having PKU, a 1:4 chance of being normal, and a 2:4 chance of being heterozygous carriers of the disorder (Gibbings, 1994). Fathers with PKU produce normal offspring; therefore, the mental retardation that occurs in children of mothers with PKU is the result of the maternal genotype (McKusick, 1994). Newborn Screening Newborn screening for PKU is effective. All children born in the United States are tested for PKU, and many other countries have incorporated this screening as part of their routine practice. The Bacterial Inhibition Test, also known as the MaylJune 1999 JOGNN 227

2 Guthrie test, which involves obtaining a few drops of the newborn s blood on filter paper, is the most commonly used screening test, is inexpensive, and is easily performed (Koch, Acosta, & Williams, 1995). The phenylalanine concentration in newborn blood is normally less than 120 umol/l (2 mg/dl). The test is considered to be positive when the phenylalanine concentration exceeds 120 umol/l. Depending on the levels that are established by the laboratory performing the screening, this value may vary. Elevated phenylalanine levels indicate a milder form of PKU known as h perphenylalanemia, whereas the diagnosis of cia+ is considered when the blood phenylalanine oncentrations are 1,200 umoyl (20 mg/dl) or greater for an infant being fed an adequate, normal diet, and the tyrosine concentration in the blood is no greater than 250 umol/l (5 mg/dl) (Erbe & Levy, 1996). Neonates who exhibit these values should be started on a low-phenylalanine diet as soon as possible to prevent the mental retardation that is seen in cases of untreated PKU (Erbe & Levy, 1996). Dietary modifications and restrictions are discussed later in this article. Accuracy of test results depends on the time at which the testing is performed. Newborn screening should not be performed before 24 hours of age. Within the first 24 hours of life, the newborn does not ingest enough breast milk or formula for phenylalanine levels to appear abnormal in the blood. Screening that is conducted during this time can result in a false-negative test and places the newborn in jeopardy of becoming severely impaired. Any child who is screened before 24 hours of age should have a repeat screen performed at 1 to 2 weeks of age (Duncan & Elder 1997). Screening needs to be conducted within the first 20 days of life to prevent adverse effects of the disease (Working Party on Phenylketonuria, 1993b). Clinical Features of Untreated PKU Neonates diagnosed with PKU who are untreated in early infancy may exhibit a variety of clinical features. Without treatment, children, although healthy at birth, become severely retarded and may develop other sequelae, such as microcephaly, seizures, hypopigmentation, and eczema (Walter, 1995). Early signs of the disease may include irritability and vomiting. The infant may have a peculiar musty odor that is due to the presence of phenylactic acid in the urine. Tyrosine, an amino acid necessary for the production of melanin, is lacking in infants with PKU; therefore these children tend to have blue eyes and are fair-haired and fairskinned. Abnormalities of bones, teeth, and gums have been observed. Children with PKU who are not treated during early childhood suffer severe mental impairment, with intelligence quotients (IQ) usually falling below 50 (Gibbings, 1994). Benefits of Early Diagnosis and Treatment When infants with PKU are identified and treated early in life, patterns of growth and development are normal (Koch, 1995). Although the mean IQ for treated patients is less than that of the general population, when the patient is on a controlled diet and maintains adequate blood phenylalanine concentrations throughout childhood, he or she can be expected to achieve a normal IQ by adulthood (Walter, 1995). After age 14, the high levels of phenylalanine in the blood no longer exhibit an adverse effect on IQ (Walter, 1995). The benefits of early treatment for the prevention of mental retardation in children with PKU have been established. Nevertheless, some people, although treated for the disease in childhood, may exhibit a range of other abnormalities. Various degrees of intellectual impairment have been observed. Children with PKU may be slower in acquiring language skills and exhibit a higher frequency of learning difficulties and behavioral problems, such as hyperactivity, anxiety, and poor concentration (Working Party on Phenylketonuria, 1993a). Although these impairments are cause for concern, most children who are treated for PKU in their early years will develop normally. Dietary restrictions that are relaxed or withdrawn before mid-childhood have been associated with decreased intellectual ability (Working Party on Phenylketonuria, 1993a). Dietary Control The treatment of PKU is the phenylalaninerestricted diet. The phenylalanine-restricted diet limits the intake of foods high in phenylalanine, such as infant formula and breast milk, to prevent the accumulation of excess levels in the blood, while at the same time providing just enough phenylalanine for adequate growth and development (Cataldo & Whitney, 1986). Initially, phenylalanine is completely removed from the diet, and the newborn is monitored until acceptable blood levels are achieved. The infant is fed special milk preparations, such as Minafen, Lofenalac, and Albumaid XP, which contain little or no phenylalanine. When blood levels fall within the acceptable range ( umol/l), precalculated amounts of breast milk or infant formula which contain phenylalanine are added to the diet. The amount of breast milk or formula that the infant receives is adjusted in response to blood phenylalanine levels (Gibbings, 1994). Breastfeeding, which was once discouraged for infants with PKU, can now be done safely. Breast milk, which contains approximately 40 mg/dl of phenylalanine, has a lower phenylalanine concentration than most infant formulas, which contain mg/dl of phenylalanine. Therefore, infants may ingest a greater 228 JOG Volume 28, Number 3

3 amount of breast milk and remain within the recommended phenylalanine limit (Duncan & Elder, 1997). Although the phenylalanine concentration in breast milk is lower than that found in infant formula, the amount of breast milk ingested is monitored to prevent phenylalanine levels from becoming too high. Mothers who choose to breastfeed will need to supplement their infant s diet with one of the special milk preparations mentioned above. To provide their infants with the nutritional, immunologic, and psychologic benefits of breastfeeding and keep the infant s phenylalanine level within a normal range, breastfeeding mothers will need to adopt a method for feeding their infants that will allow them to monitor the amount of phenylalanine that the infant is receiving. Weighing the infant before and after breastfeeding, then supplementing the feedings with a phenylalanine-free metabolic formula that provides proteins and other nutrients is one method that breastfeeding mothers may consider. An alternative method that involves having the mother pump her breasts regularly and then bottlefeed the infant with measured amounts of breast milk and metabolic formula may be used and is a more accurate means of calculating the infant s intake (Duncan & Elder, 1997). Although these methods will allow the mother to breastfeed her infant as desired, they are not without drawbacks. Difficulty in maintaining the mother s milk supply through prolonged use of a breast pump and the tedious task of frequently weighing the infant throughout the breastfeeding period may be cumbersome and frustrating to mothers (Duncan & Elder, 1997). Additional problems, such as nipple confusion, changes in feeding patterns, and coping with the stress of having a child with a metabolic disorder, may cause the family to consider an alternative feeding method or to discontinue breastfeeding completely. When helping a family choose a breastfeeding method for their infant with PKU, it may be helpful for the nurse to assess the family s reasons for wanting to breastfeed. Mothers who are mainly concerned with the nutritional and immunologic benefits of breastfeeding may find that pumping their breasts and bottlefeeding their infants with premeasured amounts of breast milk and formula is the most convenient method. On the other hand, mothers who choose to breastfeed to establish a close relationship with their child may want to weigh their infant before and after each feeding (Duncan & Elder, 1997). Women who wish to breastfeed their infants should consult with their health care providers to select a breastfeeding method that is safe, comfortable, and convenient for the mother and her infant. Blood levels of phenylalanine are drawn routinely and are used to determine the amount of phenylalanine that is to be added to the diet. It is recommended that levels be monitored biweekly until dietary control is established, weekly from infancy to 4 years of age, every 2 weeks until age 6, and then monthly thereafter. The treatment of PKU is aimed at maintaining strict phenylalanine control as long as possible into adulthood (Gibbings, 1994). The diet must provide enough kilocalories, protein, and essential nutrients for normal growth and development. Gradually, as the infant grows, solid foods are introduced. Dietitians planning meals for children with PKU choose food selections from a specific list (Cataldo & Whitney, 1986). A sample menu is shown in Table 1. Parents of children with PKU are often faced with feeding problems at mealtime. Poor appetites may be related to the undesirable taste of specially prepared foods and the gastrointestinal symptoms, such as abdominal pain, vomiting, constipation, diarrhea, and colic that commonly occur with such a diet (MacDonald et al., 1994). Parental pressure to adhere to dietary restrictions may cause the child to rebel by refusing to eat. Long-term dietary treatment is difficult and demands time and patience from parents and those affected by the disease. Throughout early childhood, parents are depended upon to supervise dietary treatments and restrictions, but as the child enters adolescence and adulthood, adherence to the diet becomes increasingly difficult. Social acceptability and peer pressures, as well as the controversy regarding the useful- Women of childbearing age who were diagnosed with PKU as neonates and who have discontinued their phenylalanine- restricted diets are at significant risk for producing a fetus with mental retardation and other congenital anomalies. ness of treatment in adulthood, may cause the adolescent or young adult to ignore dietary restrictions (Smith, 1994). Previously, health care providers believed it was safe to discontinue dietary management of PKU between the ages of 4 and 6 years. Because of the increasing number of women with early-treated PKU reaching childbearing age, however, and the discovery of subtle, yet detrimental, effects of elevated phenylalanine levels on intellectual, behavioral, and neurologic function, it has been recommended that males and females with PKU continue to adhere to dietary therapy throughout adulthood (Acosta, 1995). Mayl une 1999 JOG 229

4 - TABU 1 A Sample Menu for a Child With Phenylketonuria Breakfast VZ small banana 5 tablespoons cream of rice 2 teaspoons sugar 8 oz. Lofenalaca Mid-Morning 4 oz. orange juice Lunch 2 tablespoons raisins 2 tablespoons tomato soup (without milk) 3 tablespoons rice I-% teaspoons margarine 8 oz. Lofenalac ahfenalac is a special formula that is low in phenylalanine. Afiernoon Snuck 4 oz. Lofenalac 5 Ritz crackers supper 2 tablespoons instant potatoes (without milk) 3 tablespoons green beans 4 tablespoons vegetable and beef broth 1-'/2 teaspoons margarine '14 cup sliced peaches 8 oz. Lofenalac Bedtime Snack 2 tablespoons raisins 4 oz. Lofenalac Note. From "Diets Modified in Protein, Minerals and Water," by C.B. Cataldo & E.N. Witney, 1986, Nutrition and Diet Therapy: Principles and Practice, pp Copyright 1986 by West Publishing Company. Reprinted with permission. Effects of Mother's Untreated PKU on Pregnancy Women with PKU who are not following a phenylalanine-restricted diet and who become pregnant have an increased risk of producing offspring with severe mental retardation and other congenital anomalies (Koch et al., 1994). Unlike neonatal PKU, in which mental retardation is the result of the disease process in the newborn, the damage which occurs in maternal PKU is inflicted during embryogenesis and is the result of a high concentration of phenylalanine in the maternal circulation. Thus, the period of brain development when the insult occurs is different (Levy, Lobbregt, Barnes, & Poussaint, 1996). In neonatal PKU, because the insult to the brain does not occur until the infant starts to ingest formula and/or breast milk containing phenylalanine, early treatment can prevent the child from becoming mentally retarded. In contrast, mothers with PKU that is untreated during pregnancy will give birth to a newborn who is severely impaired. The mental retardation that occurs as a result of maternal PKU cannot be prevented or reversed during the neonatal period because the insult to the brain tissue has already taken place in utero, where brain development occurs as early as the 3rd week of gestation. Although the fetus may not have the disease, elevated concentrations of phenylalanine in maternal blood can cause grave damage to the fetus (Walter, 1995). Aside from mental retardation, intrauterine growth restriction with micro- cephaly, spontaneous abortion, and congenital heart disease are other major complications associated with maternal PKU when the mother's phenylalanine concentrations exceed 20 mg/dl (Fisch, Tagatz, & Stassart, 1993). The risk to the fetus is further increased by the normal functioning of the placenta, which aids in maintaining higher levels of amino acids in the fetus than those found in maternal circulation (McKusick, 1994). The ratio of fetal-to-maternal phenylalanine levels throughout pregnancy is approximately 1.45 to 1-00; therefore, elevated levels of maternal phenylalanine, although not hazardous to the mother, may result in fetal blood concentrations that are damaging to the fetus (Koch et al., 1995). Offspring who survive often fail to achieve normal growth and development. Identification and Management of PKU in Pregnancy To reduce the risk of fetal injury during pregnancy, health care providers need to identify women with PKU and provide them with preconception counseling and dietary management before pregnancy. There are an estimated 3,000 women of childbearing age in the United States with successfully treated PKU (Koch et al., 1994). Many of these women discontinued their phenylalanine-restricted diets in early childhood. Preconception counseling is critical so that pregnancies can be 230 JOG" Volume 28, Number 3

5 planned and the proper diet begun before conception. Patients should be educated about various methods of contraception, which should be used and continued until phenylalanine levels are controlled (Gibbings, 1994). Researchers have found that women who achieve and maintain dietary control of blood phenylalanine concentrations before pregnancy are less likely to give birth to a mentally retarded neonate than women who begin dietary treatment during the 1st trimester (Acosta, 1995). A phenylalanine-restricted diet that is begun at least 3 months before conception can reduce the risks to the fetus and provide for a positive pregnancy outcome. Women with PKU who become pregnant before seeking medical intervention should be educated about the effects of the disease on the fetus. Genetic counseling and ultrasound examination for gestational age and fetal viability should be offered, and the patient should be immediately placed on a phenylalanine-restricted diet and counseled regarding her option to either maintain or terminate the pregnancy. Dietary Therapy The goal of dietary therapy is to limit the intake of phenylalanine and establish metabolic control in the mother with PKU. Because most women with PKU discontinued treatment during middle childhood, asking them to resume and adhere to a phenylalanine-restricted diet as an adult is a problem. The recommended diet is highly restrictive, allowing only a specific number of servings of low-protein cereals, fruits, fats, and vegetables. Foods high in protein, such as dairy products, meat, fish, nuts, and eggs should be avoided because of their high phenylalanine content. Phenylalanine-free medical foods as well as prescribed phenylalanine-containing foods are added to the diet to provide the necessary protein, vitamin, and mineral requirements. Specially prepared medical foods, such as Phenex-2, Phenyl-Free, XP Maximun, and PKU-3, which contain little or no phenylalanine but provide the necessary nutrients for a well-balanced diet, are available in the United States for pregnant women with PKU (Acosta, 1995; Koch et al., 1995). Many women find it difficult to adhere to these recommendations because of the undesirable taste of these products, and many find it difficult to withstand the social pressures to eat pro- scribed foods. For these women to establish nutritional control and become accustomed to adhering to the drastic changes in their eating habits, a phenylalaninerestricted diet should be developed and initiated at least 3 months before a planned pregnancy (Acosta, 1995; Waisbren, Hamilton, St. James, Shiloh, & Levy, 1995). Because of the positive amino acid gradient across the placenta, the phenylalanine concentrations in pregnancy need to be strictly controlled as in infancy and early childhood (Fisch et al., 1993). Other factors in pregnancy, such as variations in food preferences and the nausea and vomiting commonly experienced during the 1st trimester, can alter maternal blood phenylalanine concentrations and further increase the potential for nonadherence to the diet (Acosta, 1995). Access to the specially prepared medical food is necessary for successful therapy. Women with PKU who lack financial support and knowledge of social resources may find it difficult to adhere to dietary restrictions because of the cost of treatment. During the 3 months prior to conception and the 9 months of pregnancy costs can add up to approximately $4,500 for medical food (Acosta, 1995; Koch et al., 1995). Patients should be aware that while phenylalanine-free medical foods may be purchased individually from a medical supply store, they may be obtained from the state s Supplemental Food Program for Women, Infants and Children (WIC); Medicaid; or in some cases, paid for by insurance. Patient education is essential to achieve a positive pregnancy outcome. Mothers who are well-educated in the disease process, the potentially hazardous effects to the fetus, and the importance of dietary control before and throughout pregnancy, are more likely to comply with nutritional therapy. Pregnancy should be discouraged if the woman lacks the motivation, commitment, intellectual capacity, or financial support to maintain the low-protein diet (Fisch et al., 1993). Monitoring Metabolic and Dietary Control in Pregnancy Throughout pregnancy, the metabolic function and nutritional status of the woman with PKU must be monitored. Individual dietary requirements and phenylalanine tolerance vary during pregnancy among women with PKU. Phenylalanine concentrations may fluctuate daily; therefore, to maintain levels that would guarantee the birth of an unaffected infant, it would be necessary to test the mother s blood levels daily (Fisch et al., 1993). This approach, however, is neither convenient nor cost-effective. Although no formula exists for determining how frequently the phenylalanine level needs to be checked, a more practical approach is to check blood phenylalanine levels twice weekly through- MaylJune 1999 JOGNN 231

6 out pregnancy. Table 2 suggests specific time intervals for monitoring maternal nutritional status and fetal well-being. Nurses who are knowledgeable about the disease can help women with PKU to begin nutritional therapy before conception and provide the education and support needed for optimal pregnancy outcome. Although the exact phenylalanine concentration that would provide for the greatest possible pregnancy outcome is unknown, a restricted diet, which maintains blood concentrations of phenylalanine between 60 and 180 umol/l, has been suggested to achieve an optimal fetal outcome (Acosta, 1995; Koch et al., 1995). Monitoring of blood phenylalanine levels and frequent changes in dietary restrictions are necessary to prevent these levels from dropping below the therapeutic range. A phenylalanine blood concentration of less than 60 umoyl has been shown to be harmful to both maternal nutrition and fetal brain development (Acosta, 1995; Koch et al., 1995). TABLE 2 Suggested Timetable for Monzhdng Pregnant Women With Pbenylketonuria Who Are Following a Pbenylalanine- Restricted Diet I Data Nutrient intake from 3-day records Blood phenylalanine concentration Plasma amino acid concentrations Plasma albumin concentration Plasma ferritin concentration Plasma selenium and zinc concentrations Height Weight Fetal growth Schedule Twice weekly Twice weekly Initially Beginning at weeks of gestation Note. From Nutrition Support of Maternal Phenylketonuria, by P. Acosta, 1995, Seminars in Perinatology, 19, p Copyright 1995 by W.B. Saunders Company. Reprinted with permission. Women who become pregnant with phenylalanine levels greater than 700 umol/l may be advised to terminate the pregnancy because of the increased risk for mental retardation and other associated fetal anomalies (Fisch et al., 1993; Working Party on Phenylketonuria, 1993 b). Pregnant women with PKU who are following a phenylalanine-restricted diet shoyld not be given prenatal vitamin supplements. The 6edical foods that the women ingest as part of their dietary program are vitamin-enhanced and contain all the vitamins, minerals, and proteins that are needed for a well-balanced diet. Taking prenatal vitamins in addition to those supplied by the prescribed medical foods could result in increased levels of certain vitamins, such as A and D, that could be teratogenic to the fetus (Koch et al., 1995). On the other hand, if the woman is not following her diet properly and fails to ingest the recommended amount of prescribed medical food, serious vitamin and mineral deficiencies may occur. Plasma levels of tyrosine and other amino acids, as well as zinc, iron, and selenium levels should be monitored at least once a month during pregnancy to avoid abnormally low levels, which may have a detrimental effect on maternal health and fetal well-being (AFosta, 1995). Just as in a normal preg$ancy, mothers with PKU will need to have routine monitoring of weight gain throughout their pregnancy. In addition to monitoring phenylalanine levels, periodic evaluation of weight gain is important in determining whether the mother is receiving adequate nutrition. Maternal weight gain has been correlated with fetal outcome and should be considered when establishing a plan of care for pregnant women with PKU (Michals et al., 1996). For women with PKU who are of normal weight at the time of conception, an average total weight gain of kg is considered appropriate. Underweight women will need to gain kg and overweight women between kg (Koch et al., 1995). Antenatal Fetal Assessment Monitoring of the pregnancy with serial ultrasound scans is important to assess for adequate fetal growth and development. Level I1 scans are indicated for early detection of fetal congenital heart defects and other major anomalies (Acosta, 1995; Fisch et al., 1993; Koch et al., 1995). First trimester ultrasounds can be used to assess gestational age as well as identify nonviable pregnancies. Precise knowledge of gestational age is important because pregnancy outcome is greatly dependent upon the timing of dietary control. Early detection of a nonviable pregnancy can prevent the burden of continuing a costly, highly restricted diet and frequent metabolic 232 JOGNN Volume 28, Number 3

7 monitoring (Levy, Lobbregt, Platt, & Benacerraf, 1996). Second and third trimester level I1 ultrasounds are valuable in identifying fetal cardiac anomalies often associated with maternal PKU, as well as assessing interval growth. Third trimester scans are useful in identifying some cases of microcephaly and cardiac anomalies that may have been missed on previous scans (Levy, Lobbregt, Platt, and Benacerf, 1996). Serial ultrasound scans, beginning at weeks gestation, should be incorporated into the care plan for all pregnant mothers with PKU (Koch et al., 1995). Information about fetal growth and development can be reassuring for parents and health care providers. Early detection of fetal abnormalities may enable parents to make informed decisions about termination of pregnancy or to adjust and prepare for a potentially adverse outcome. Neonatal Assessment After delivery, the neonate should receive a complete physical examination and be observed for any signs of neurologic impairment or other malformations. Pediatricians need to be notified of infants born to mothers with PKU to plan for long-term assessment of growth and development. Although the incidence of PKU in infants born to mothers with PKU is higher than the general population, most infants are not born with the disease. Routine screening for PKU will be performed on the neonate and in the event of a positive result, parents will need to be educated about nutritional management. Early access to specialists, such as dietary counselors and neurologists, is needed to provide for long-term care (Fisch et al., 1993). Parents may also be offered information about community support groups, such as the National Society for Phenylketonuria and the March of Dimes Birth Defects Foundation, which can provide information and support to families of children with PKU. Additional information and resources can be obtained by writing to the March of Dimes or ing their internet address: publiceducation@modimes.org. Conclusion As the number of women with early-treated PKU entering childbearing age increases, nurses need to be knowledgeable about the disease. The key to a successful pregnancy outcome is early detection and initiation of nutritional therapy before conception. Women with insufficient education about the disease who are suddenly confronted with dietary restrictions that are both costly and undesirable may not adhere to their diet. A multidisciplinary team approach is needed to provide for high quality continuity of care. Nurses can be valu- able in providing the education and support needed for an optimal pregnancy outcome. Future studies that examine the efficacy of nursing interventions and patient education on dietary adherence and pregnancy outcome may help to expand our understanding of the disease and suggest alternative strategies for the management of maternal PKU. REFERENCES Acosta, P. (1995). Nutrition support of maternal phenylketonuria. Seminars in Perinatology, 2 9(3), Cataldo, C.B., & Whitney, E.N. (1986). Diets modified in proteins, minerals and water. In C.B. Cataldo & E.N. Whitney (Eds.), Nutrition and diet therapy: Principles and practice (pp ). St. Paul, MN: West Publishing Co. Duncan, L.L., & Elder, S.B. (1997). Breastfeeding the infant with PKU. Journal of Human Lactation, 13(3), Erbe, R.W., & Levy, H.L. (1996). Neonatal screening. In D.L. Rimoin, J.M. Connor, & R.E. Ryeritz (Eds.), Principles and practices of medical genetics (pp ). New York: Churchill Livingston. Fisch, R.O., Tagatz, G., & Stassart, J.P. (1993). Gestational carrier-a reproductive haven for offspring of mothers with phenylketonuria (PKU): An alternative therapy for maternal PKU. Journal of Inherited Metabolic Diseases, 26(6), Gibbings, B. (1994). Keeping phenylketonuria under control. Modern Midwife, 4(10), Imarmura, T., Shintaku, H., Nakajima, T., Sawada, Y., Isshiki, G., & Oura, T. (1993). Experimental research on a new treatment for maternal phenylketonuria (PKU). Advances in Experimental Medicine and Biology, 338, Koch, R., Acosta, P.B., & Williams, J.C. (1995). Nutritional therapy for pregnant women with a metabolic disorder. Clinics in Perinatology, 22(1), 2-8. Koch, R., Levy, H.L., Matalon, R., Rouse, B., Hanley, W.B., Trefz, F., Azen, C., Friedman, E.G., de la Cruz, F., Guttier, F., & Acosta, P.B. (1994). The international collaborative study of maternal phenylketonuria: Status report Acta Paediatrica (Suppl. 407), Levy, H.L., Lobbregt, D., Barnes, P.D., & Poussaint, T.Y. (1996). Maternal phenylketonuria: Magnetic resonance imaging of the brain in offspring. Journal of Pediatrics, 228(6), Levy, H.L., Lobbregt, D., Platt, L.D., & Benacerraf, B.R. (1996). Fetal ultrasonography in maternal PKU. Prenatal Diagnosis, 2 6(6), MacDonald, A., Rylance, G.W., Asplin, D.A., Hall, K., Harris, G., & Booth, I.W. (1994). Feeding problems in young PKU children. Acta Paediatrica (Suppl. 407), McKusick, V.A. (1994). Autosomal recessive catalog. In V.A. McKusick (Ed.), Mendelian inheritance in man, A catalog of human genes and genetic disorders, V01.2 (1 Ifh ed., pp ). Baltimore: Johns Hopkins University Press. MaylJune 1999 JOGNN 233

8 Michals, K., Acosta, P.B., Austin, V., Castiglioni, L., Rohr, F., Wenz, E., & Azen, C. (1996). Nutrition and reproductive outcome in maternal phenylketonuria. European ]ournal of Pediatrics, 155 (Suppl. I), Smith, I. (1994). Treatment of phenylalanine hydroxylase deficiency. Acta Paediatrica (Suppl. 407), Waisbren, S.E., Hamilton, B.D., St. James, P.J., Shiloh, S., & Levy, H.L. (1995). Psychosocial factors in maternal phenylketonuria: Women's adherence to medical recommendations. American Journal of Public Health, 85(12), Walter, J.H. (1995). Late effects of phenylketonuria. Archives of Disease in Childhood, 73(6), Working Party on Phenylketonuria. (1993a). Phenylketonuria due to phenylalanine hydroxylase deficiency: An unfolding story. Report of Medical Research Council Working Party on Phenylketonuria. British Medical Journal, 306, Working Party on Phenylketonuria. (1993b). Recommendations on the dietary management of phenylketonuria. Report of Medical Research Council Working Party on Phenylketonuria. Archives of Disease in Childhood, 68(3), Robin B. Kirby is a perinatal clinical specialist at St. Peter's University Hospital in New Brunswick, NJ. Address for correspondence: Robin B. Kirby, RNC, MSN, CRNC c/o St. Peter's University Hospital, Department of Education and Development, 254 Easton Avenue, New Brunswick, NJ JOGNN Volume 28, Number 3