Factors influencing outcomes in the offspring of mothers with phenylketonuria during pregnancy: the importance of variation in maternal blood phenylalanine.

BACKGROUND

Developmental delay in the offspring of women with phenylketonuria (PKU) can be prevented by maintaining maternal blood phenylalanine (Phe) within a target range (100-250 micromol/L).

OBJECTIVE

We aimed to analyze outcomes in the offspring of women with PKU during pregnancy and to identify prognostic factors.

DESIGN

Occipitofrontal circumference at birth (OFC-B); developmental scores [developmental quotient (DQ) and intelligence quotient (IQ)]at 1, 4, 8, and 14 y; and the time of starting a Phe-restricted diet (before or after conception) were collected. The influence of maternal Phe concentrations during pregnancy on offspring outcomes also was assessed.

RESULTS

The study included 105 children born to 67 mothers with PKU. Mean (+/-SD) OFC-B z scores did not differ between the preconception and postconception diet groups (0.42 +/- 1.24 and -0.96 +/- 1.19, respectively). DQ at 1 y and IQ at 8 y were higher in offspring from the preconception diet group than in offspring from the postconception diet group [DQ: 107 +/- 13.8 and 99.3 +/- 13.3, respectively (P = 0.014); IQ: 110.6 +/- 14.8 and 91.2 +/- 23.9, respectively (P = 0.005)]. Maternal Phe concentrations correlated negatively with DQ and IQ scores, and variations (SD) in all maternal blood Phe correlated negatively with 4-, 8-, and 14-y IQ scores (r = -0.385, -0.433, and -0.712; P = 0.002, 0.008, and 0.031, respectively), even when concentrations were consistently within the target range.

CONCLUSIONS

The study suggests that women with PKU should start a Phe-restricted diet before conception. Maintenance of maternal blood Phe within the target range predicts good offspring outcomes, but variations even within that range should be avoided.