School of Medicine

Department of Genetics

Pregnancy and Phenylketonuria (PKU)


Gabriella Pridjian, MD

Girls or women with PKU can have healthy children as long as they are aware of and maintain strict adherence to their low phenylalanine diet throughout their pregnancy. It is well known that women with poorly controlled PKU during a pregnancy put their baby at risk for delayed developmental, mental retardation, poor head growth (microcephaly), poor overall growth, heart defects, and other structural birth defects. These complications are due to the ability of high levels of phenylalanine and its metabolites to directly cause birth defects, and not because the baby has PKU. The closer to normal the mother's phenylalanine level in her blood plasma is to normal, the less likely these complications occur. (The blood plasma is the watery part of the blood.)

The most critical time period of fetal development is during the first three months of pregnancy when the organs systems form. It is believed that it is during this time period that high phenylalanine and its metabolites in the mothers' blood plasma can cross the placenta and directly effect the developing embryo by inducing birth defects. However, in the latter months the fetal brain continues to mature and abnormally high levels of phenylalanine can also influence brain development at that time. Therefore, it is important to maintain normal blood phenylalanine levels throughout pregnancy.

Ideally, girls or women with PKU should have counseling and dietary adjustments before becoming pregnant. For those girls who have been on a low phenylalanine diet all along, preparing for pregnancy becomes easy, because they are essentially already metabolically prepared. The ideal range for plasma phenylalanine levels before and during pregnancy is 2 to 8 mg/dl, the same range that is considered excellent control in a nonpregnant individual. Girls who are not on a low phenylalanine diet at the time they decide they want to be pregnant have a more difficult time adhering to the diet, but it is possible.

Girls who have high plasma phenylalanine because they are not on a low phenyalanine diet and become pregnant have already exposed the baby by the time they find out they are pregnant. Even though they might get into good control quickly, their baby is still at risk. Since pregnancy is often unplanned or accidental, it would be ideal if girls with PKU maintain normal levels all the time.

Dietary counseling is important before and throughout pregnancy and the postpartum (after delivery) period. For adequate nutrition to supply the developing baby, it is recommended that the mother's caloric intake increase by about 300 Kcalories per day. This can be modified to an extra 100 Kcalories per day the first three months of pregnancy, an extra 200 Kcalories the middle three months of pregnancy, and 300 extra Kcalories the last three months. The amount of protein and phenylalanine that is required to supply adequate nutrition to the baby, yet not cause elevated levels increases as pregnancy progresses. Thus, very careful monitoring of levels and diet is required. Breast feeding can be successfully accomplished by women with PKU. It is important to remember that the highest caloric requirement of the entire pregnancy is during breast feeding. An extra 500 Kcalories per day is recommended during this time. Again, dietary counseling is important in this period as well.

Also important for overall health of the pregnancy is vitamin supplementation, in particular folic acid. If a women takes folic acid before and during the pregnancy, her baby has less of a chance of being born with an open spinal defect (spina bifida, neural tube defects). The recommended dose is 400 micrograms or 0.4 milligrams per day. Most vitamin supplements now contain this quantity. While taking supplemental folic acid may not decrease the chance that a baby will have birth defects or growth problems related to poor phenylalanine control, it will help protect the baby from developing spinal defects.

Because nutritional needs change during a pregnancy, monitoring of phenylalanine and tyrosine levels during pregnancy is performed weekly. Dietary adjustments are made accordingly. Most often, specialized dieticians who are familiar with metabolic illnesses are required to help regulate the diet. Occasionally, because of the severity of the nausea and vomiting and lack of appetite associated with early pregnancy, women with PKU are hospitalized for nutrition. Usually, intravenous (I.V.) nutrition is administered. When women with PKU don't eat enough, their bodies begin to break down their own protein releasing phenylalanine. This leads to elevation of phenylalanine in their blood. This phenomenon is sometimes hard to understand. Even though the mother is not eating foods high in phenylalanine (she isn't eating much at all), her blood value can be very high. The treatment of this is to give nutrition IV until the mother can eat her normal PKU diet again. Occasionally, women require hospitalization later in the pregnancy if it is just too difficult to keep the phenylalanine in a normal range.

During the pregnancy, the baby is monitored by detailed (targeted) ultrasound to assess growth and to look for birth defects. This is usually done by a specialist who has extra training in detailed ultrasound and is aware of the birth defects and growth problems that babies of PKU mothers can have.

Most babies of women with PKU are not born with PKU. Whether the baby gets PKU is not related to the degree of metabolic control that the mother had during the pregnancy. PKU is an autosomal recessive genetic disorder. PKU individuals lack normal genes (we have two copies) that make the enzyme that metabolizes phenylalanine. Each baby born of a mother who has PKU will at least carry one nonfunctioning gene for the enzyme (that he or she got from his mother). If the baby inherits a normal gene from the father, the baby will only be a carrier for PKU and be essentially normal in metabolism of phenylalanine (not have PKU). If the baby inherits an abnormal PKU gene from the father, the baby will be born with PKU. The probability of inheriting an abnormal PKU gene from the father is very unlikely unless the father has PKU also, or if PKU runs in his family, or he is related to the mother in some way. All these situations make the chances that the father has a nonfunctioning PKU gene higher. Overall, if a mother with PKU has a child with a healthy father who is not related to her nor has PKU in his family, the chance that the baby will get PKU is estimated to be 1 in 800, or very unlikely. This is a general estimate. Couples in which one individual has PKU are encouraged to obtain specific genetic counseling to address the particular risk for them.

Males with PKU appear not to have major difficulty in production of sperm and thus fathering children. The wife of a man with PKU does not have extra problems becoming pregnant, or having a healthy baby. There appears to be no increase in birth defects if the father of a baby has PKU. It should be remembered that all couples have a small chance of having a baby with a birth defect or genetic problem even if they do not have PKU.

Overall, pregnancy in women with PKU can result in a healthy baby if very close attention is paid to diet and monitoring. Ideally, normal phenylalanine levels should be achieved before pregnancy occurs. In addition to their regular doctor, pregnant women with PKU should be cared for by a specialist (usually a maternal-fetal medicine specialist or a geneticist) and a metabolic nutritionist (specialized dietician). Together, this team will help the pregnant women maintain good metabolic control. However, the most important person on the team is the pregnant women herself. After all, she has the final control with regards to the food she eats or doesn't eat while she is pregnant.