Women with phenylketonuria (PKU) can deliver healthy babies if they maintain an appropriate diet that keeps blood phenylalanine levels in normal range prior to and throughout pregnancy, a study from China suggests.
The study, “The first study of successful pregnancies in Chinese patients with Phenylketonuria,” was published in the journal BCM Pregnancy and Childbirth.
PKU results in elevated levels of the amino acid phenylalanine in the blood, which can lead to mental disabilities and, in severe cases, seizures and brain damage.
Failure to keep phenylalanine levels in check may compromise development of the fetus, and could cause developmental delays after birth. Researchers suggest that women with poor diet compliance may benefit from medications such as Kuvan (sapropterin dihydrochloride).
Early dietary interventions can effectively manage PKU, and with the advent of newborn screening, more patients are reaching adulthood with normal intellectual and physical development. But whether appropriate disease management can help PKU women reaching childbearing age deliver healthy babies is still largely unreported in China.
A team of researchers investigated if maintaining phenylalanine within the suggested target range (120–360 micromoles per liter, or mcmol/L) could reduce the post-natal complications that often occur in patients’ offspring, such as low birth weight, impaired intellectual development, and heart defects. The goal was to help guide physicians and obstetricians in the management of these women.
The study included 10 married women with PKU who sought prenatal counseling for a future pregnancy. Patients were educated to calculate phenylalanine intake, and were asked to keep their phenylalanine levels in normal range in the three months before conception and throughout pregnancy, while maintaining an adequate diet for the developing fetus.
During pregnancy, women underwent at least five ultrasound examinations to detect structural and growth abnormalities, and were advised to visit their local prenatal care service at least once a month in the first two trimesters, with more regular visits in the third one. Congenital heart defects also were screened.
The patients were all of Han ethnicity and none of their partners had PKU-causing mutations. By the end of 2017, six women had become pregnant, at a mean age of 26.3 years. Two women had experienced spontaneous abortions due to inadequate dietary treatment.
Generally, pregnancy went without complications such as anemia or gestational high blood pressure. While all women started a phenylalanine-free diet for a mean of 5.5 months before pregnancy, mean phenylalanine blood levels were above normal range in the first trimester (478.3 mcmol/L). They then dropped to normal values in the second (193.7 mcmol/L) and third (151.4 mcmol/L) trimesters.
Overall, the mean period of gestation was 38.2 weeks, with all babies being born full-term without heart defects or other severe malformations. Weight and height at birth also were normal in most babies, with only two showing low birth weight; their mothers had inadequate metabolic control during pregnancy, deemed as fewer than 70% of phenylalanine measurements within normal range. One of these children also had mild delays in language and motor development.
The team also found that a greater control of blood phenylalanine levels correlated with a better developmental quotient, which determines a range of psychosocial skills, such as social development, attention span, language, and both fine and gross motor function.
Together, the findings suggest that elevated blood levels of phenylalanine during pregnancy are associated with worse offspring outcomes and that “metabolic control during pregnancy is beneficial,” the researchers wrote.
“In maternal PKU patients with poor compliance to dietary treatment, sapropterin dihydrochloride [Kuvan] may be an option to improve the management of blood Phe [phenylalanine] levels,” they concluded.