MATERNAL MILD HYPERPHENYLALANINEMIA - AN INTERNATIONAL SURVEY OF OFFSPRING OUTCOME

Maternal phenylketonuria (PKU) has adverse effects on the offspring in cluding microcephaly, mental retardation, congenital heart disease, an d intrauterine growth retardation. Maternal non-PKU mild hyperphenyala ninaemia (MHP) is believed to be benign, but whether there may be long -term consequences to offspring is unclear. In an international survey we have obtained information about 86 MHP mothers with MHP (blood phe nylalanine 167-715 mu mol/L), their 219 untreated pregnancies, and 173 offspring. Spontaneous fetal loss (13% of pregnancies), congenital he art disease (2.3% of offspring), and severe non-cardiac anomalies (2.9 % of offspring) occurred at frequencies within expected limits for the general population. For weight and length at birth the median percent ile was the 50th but that for birth head circumference was the 25th. M edian z-scores for birth length and head circumference were significan tly lower for offspring of mothers with phenylalanine concentrations a bove 400 mu mol/L than for those whose mothers had lower values (p=0.0 5 and p=0.005, respectively). The median intelligence quotient (IQ) of the offspring (3-27 years) was 100 for those whose mothers had higher phenylalanine concentrations and 108 for those of the lower phenylala ninaemia group. However, offspring IQ correlated slightly more closely with maternal IQ (r=0.53, p<0.01) than with maternal phenylalanine co ncentration (r=0.45, p=0.02). Maternal MHP does not seem to have serio us consequences for the fetus. A maternal phenylalanine concentration of less than 400 mu mol/L does not warrant intervention. Nevertheless, maternal blood phenylalanine above this value is associated with slig htly lower birth measurements and offspring IQ than lower maternal blo od phenylalanine concentrations.