Outcome at age 4 years in offspring of women with maternal phenylketonuria: the Maternal PKU Collaborative Study.
BACKGROUND
Untreated maternal phenylketonuria (PKU) increases risk for developmental problems in offspring. The extent to which this risk is reduced by maternal dietary therapy at various stages of pregnancy is not known.


OBJECTIVE
To determine whether dietary treatment during pregnancy of women with PKU affects developmental outcomes of offspring.


METHODS
The Maternal PKU Collaborative Study, an ongoing, longitudinal prospective study begun in 1984.


METHODS
A total of 78 metabolic clinics and obstetrical offices in the United States, Canada, and Germany.


METHODS
A total of 253 children of women with PKU (n = 149), with untreated mild hyperphenylalaninemia (n = 33), or without known metabolic problems (comparison group; n = 71) were followed up to age 4 years.


METHODS
Women with PKU were offered a low-phenylalanine diet prior to or during pregnancy with the aim of maintaining metabolic control (plasma phenylalanine < or =10 mg/dL [< or =605 micromol/L]). Women with mild hyperphenylalaninemia, who had plasma phenylalanine levels of no more than 10 mg/dL (605 micromol/L) on a normal diet, were not treated.


METHODS
Children's scores on cognitive and behavioral assessments (McCarthy Scales of Children's Abilities, Test of Language Development, Achenbach Child Behavior Checklist, Vineland Adaptive Behavior Scales, and Home Observation for Measurement of the Environment), compared by maternal metabolic status at 0 to 10 weeks', 10 to 20 weeks', and after 20 weeks' gestation.


RESULTS
Scores on the McCarthy General Cognitive Index decreased as weeks to metabolic control increased (r = -0.58; P<.001). Offspring of women who had metabolic control prior to pregnancy had a mean (SD) score of 99 (13). Forty-seven percent of offspring whose mothers did not have metabolic control by 20 weeks' gestation had a General Cognitive Index score 2 SDs below the norm. Overall, 30% of children born to mothers with PKU had social and behavioral problems.


CONCLUSIONS
Our data suggest that delayed development in offspring of women with PKU is associated with lack of maternal metabolic control prior to or early in pregnancy. Treatment at any time during pregnancy may reduce the severity of delay.
Waisbren
S E
SE
Genetic Service, Children's Hospital, Boston, Mass 02115, USA. waisbren@al.tch.harvard.edu
Hanley
W
W
Levy
H L
HL
Shifrin
H
H
Allred
E
E
Azen
C
C
Chang
P N
PN
Cipcic-Schmidt
S
S
de la Cruz
F
F
Hall
R
R
Matalon
R
R
Nanson
J
J
Rouse
B
B
Trefz
F
F
Koch
R
R
D002652:Child Behavior; D002675:Child, Preschool; D003071:Cognition; D002658:Developmental Disabilities / Q000175:diagnosis / Q000209:etiology; D005260:Female; D006801:Humans; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D010661:Phenylketonurias / Q000178:diet therapy* / Q000503:physiopathology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000178:diet therapy*; D011256:Pregnancy Outcome; D011581:Psychological Tests