The North American Maternal Phenylketonuria Collaborative Study, developmental assessment of the offspring: preliminary report

Abstract

Preliminary results of 2-year Bayley and 4-year McCarthy test scores are presented. To date numbers are too small to statistically correlate:- offspring from pregnancies in which diet was started prior to conception, offspring from pregnancies with phenylalanine (Phe) levels of 120-360 mumol/l versus 360-600 mumol/l, influence of home environment, influence of maternal nutrition, language development, behaviour/hyperactivity, Revised Wechsler Intelligence Score, school performance and learning disabilities. Two-year Bayley scores (mental and motor) revealed a median developmental quotient of 113 in 58 offspring from control pregnancies, 104 in 19 offspring from untreated "non-phenylketonuria (PKU) mild hyperphenylalaninaemia" (natural Phe levels < 600 mumol/l) pregnancies, 104 in 32 offspring from pregnancies whose Phe levels decreased on treatment to < 600 mumol/l by 10 weeks gestation and remained in that range for the remainder of the pregnancy, 98 in offspring from 32 pregnancies where permanent control was not achieved until 10-20 weeks and 72 in offspring from 51 pregnancies where control was not attained until after 20 weeks gestation. IQ scores determined by the McCarthy test at age 4-5 years revealed a mean of 112 in 43 offspring of control mothers, 99 in 12 offspring of "non PKU mild hyperphenylalaninaemia" women, 93 in 14 offspring whose mother's Phe levels were continuously under 600 mumol/l by 10 weeks gestation, 88 in 24 offspring from pregnancies in metabolic control by 10-20 weeks and 73 in 28 offspring of pregnancies not in metabolic control until after 20 weeks gestation. These preliminary results suggest that early and adequate dietary treatment during pregnancy in maternal PKU may provide some protection to the fetus for later intellectual development but much more data is required before definitive statements about cognition can be made.

Brain MRI Abnormalities in Phenylketonuria

“…The results of the volumetric measurements are summarized in Table 1. These findings of Pfaendner et al [13] are in accordance with other, nonquantitative imaging studies [8,[16][17][18][19]. However, it has not been previously reported that the size of the hippocampus is reduced in PKU.…”

Effect of Maternal Blood Phenylalanine Level on Mouse Maternal Phenylketonuria Offspring

“…Most such individuals are mentally normal and are now of child bearing age. Unfortimately, most of them have discontinued the PHErestricted diet since childhood and have high blood PHE levels Hanley et al, 1996). It is now clear that women with PKU not treated prior to conception are at increased risk of having a pregnancy that results in serious fetal damage.…”

Developmental and neuropsychological outcome in children born to mothers with phenylketonuria

“…Table 3 presents data from a broader sample of the infants from the MPKUCS at 2 years of age. Among offspring whose mothers attained metabolic control by 20 weeks' gestation, the median DQ was within the average range, whereas the median DQ of offspring whose mothers were not in metabolic control until after 20 weeks' gestation was in the range of mental retardation [Hanley et al, 1996].…”

“…Psychological data on only a small number of school-age subjects have been published [Hanley et al, 1996]. The mean IQ of maternal PKU offspring followed a similar pattern: 93 for offspring whose mothers attained metabolic control by 10 weeks; 88 for those whose mothers attained metabolic control between 10 and 20 weeks; and 73 for those whose mothers were not in control until after 20 weeks.…”

“…Thereafter, they are evaluated every 2-3 years, through age 10 years. Results indicate that maternal phenylalanine levels, even during early gestation, have an impact on birth weight and head circumference [Platt et al, 1992;Rouse et al, 1997], and on the child's developmental course [Hanley et al, 1996]. However, the relationships proved to be complex.…”