Maternal Phenylketonuria: An International Study (original) (raw)
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The international collaborative study of maternal phenylketonuria: status report 1998
European Journal of Pediatrics, 2000
The Maternal PKU Study began in 1984 and during the intervening years, 572 pregnancies in women with hyperphenylalaninemia (HPA) and 99 controls and their outcomes have been evaluated. Among Women with HPA who delivered a live infant, only 15.9% were treated and in metabolic control preconceptionally; however, another 18.4% were in control by 10 weeks. Compared to the results reported by Lenke and Levy in 1980, there is a marked improvement in outcome with treatment. Microcephaly was unusual in preconceptionally treated pregnancies with wellcontrolled phenylalanine-restricted diets. Even in pregnancies that established control after conception but before the 8th week, congenital heart disease did not occur in the offspring; however, it did occur in 12% of pregnancies not achieving control until after 10 weeks of pregnancy. The recommended level of blood phenylalanine during pregnancy is 120-360 mol/L. Best results were obtained by close cooperation between the attending obstetrician and a metabolic team experienced in the care of persons with phenylketonuria.
Obstetrical & Gynecological Survey, 2000
HENYLKETONURIA (PKU) IN women increases the risk to their offspring for adverse outcomes. In the offspring of untreated women with maternal PKU, there is a 92% risk for mental retardation, 73% risk for microcephaly, 40% risk for low birth weight, and 12% risk for congenital heart disease. The precise mechanism of fetal damage in maternal PKU is still unknown, although it is clear that the abnormal intrauterine environment harms the fetus. Treatment with a phenylalanine-restricted diet begun prior to pregnancy reduces these risks. 5 However, the extent to which risks are reduced in late or inadequately treated pregnancies has not been clearly established.
Nutrition and reproductive outcome in maternal phenylketonuria
European Journal of Pediatrics, 1996
Maternal weight gain and intake of selected nutrients were correlated with plasma phenylalanine (Phe) concentrations and reproductive outcomes (in 150 and 142 subjects respectively) in the Maternal PKU Collaborative Study. Daily protein intake was negatively correlated with plasma Phe concentration. Birth length, weight and head circumference of offspring were negatively influenced by the length of time required for the maternal plasma Phe to decline below 600 ~tmol/1 (10 mg/dl) and positively influenced by weight gain of mother as a percentage of recommended weight gain. Birth weight and length were positively correlated with maternal protein and energy intakes. During the first trimester, intakes of fat, calcium, phosphorus, vitamin A and fo-late were significantly greater in women who had a good reproductive outcome than by women who had a poor outcome. In addition to plasma Phe control in maternal phenylketonuria (PKU), maternal weight gain and dietary intake of protein, energy and fat were correlated with outcome. Therefore, nutrient intake and maternal weight gain should be considered along with plasma Phe concentration when managing the therapy of a pregnant woman with PKU.
Maternal Phenylketonuria Collaborative Study (MPKUCS)—The 'outliers
Journal of Inherited Metabolic Disease, 2000
Analysis of outcome data from 305 of the 414 offspring from the Maternal Phenylketonuria Collaborative Study (MPKUCS), plus 70 control offspring, revealed signi¢cant de¢cits in the IQ (intelligence quotient), as measured by the Wechsler Intelligence Scale for Children^Revised (WISC-R), when maternal metabolic control during pregnancy was delayed and/or inadequate. There were, however, 23 'outliers' (7.5% of the 305) in which the offspring's intellectual IQ was worse (n ¼ 10) or better (n ¼ 13) than expected. The aim of this study was to determine whether collection parameters were incomplete or whether these subjects were true biological variants in£uenced by other undetected factors or, perhaps, by modi¢er genes. Among the 10 offspring whose intellectual functioning was worse than expected, additional complications were uncovered that could explain the poor outcome. Four of the 13 offspring with higher than expected IQ had mothers with mild variants of PKU in which the insult to the fetus would not be expected to be as profound. For the other nine offspring whose intellectual performance was better than expected, there was no explanation, based on the parameters studied. We hypothesize that modi¢er genes will, at times, protect the fetus despite high maternal concentrations of phenylalanine. Not all offspring from the same (untreated) PKU mother may be similarly affected. Finding the source of these modi¢ers might effect the treatment of MPKU.
American Journal of Clinical Nutrition, 2012
Background: Untreated maternal phenylketonuria or hyperphenylalaninemia may result in nonphenylketonuric offspring with neonatal sequelae, especially intellectual disability, microcephaly, and congenital heart disease (CHD). Dietary treatment to control phenylalanine concentrations can prevent these sequelae. Objective: We aimed to present an overview of reported pregnancy complications and neonatal sequelae of maternal phenylketonuria or hyperphenylalaninemia in untreated and treated pregnancies. Design: A MEDLINE and EMBASE search was conducted for case reports and case series that assessed maternal phenylketonuria or hyperphenylalaninemia during pregnancy. Pregnancy complications (spontaneous abortion, intrauterine-fetal-death, and preterm delivery) and neonatal sequelae [small for gestational age (SGA), microcephaly, CHD, intellectual or developmental disabilities (IDDs), and facial dysmorphism (FD)] were analyzed. Fifteen unpublished pregnancies from our clinic were added. Results: We retrieved 196 pregnancies, of which 126 pregnancies were untreated and 70 pregnancies were treated. The occurrence of pregnancy complications was not significantly different between untreated and treated pregnancies. Except for SGA, all neonatal sequelae were more frequent in untreated pregnancies. Moreover, the occurrence of SGA, microcephaly, and IDDs was significantly related to the mean phenylalanine concentration in each trimester, whereas the occurrence of FD was related only to the first trimester. Conclusions: We present the largest cohort of untreated pregnant women with phenylketonuria or hyperphenylalaninemia since 1980. The results follow the general pattern reported by other researchers. We underline that the treatment of pregnant women with phenylketonuria or hyperphenylalaninemia is of great importance to prevent neonatal sequelae. We strongly recommend starting treatment before conception because we showed the deleterious effect of an increased mean first-trimester phenylalanine concentration on FD.
Impact of the phenylalanine hydroxylase gene on maternal phenylketonuria outcome
Pediatrics, 2003
The aim of the present study was to examine to what extent maternal and offspring phenylalanine hydroxylase (PAH) genotypes in conjunction with maternal IQ and dietary control during pregnancy are related to cognitive development in offspring of women with phenylketonuria (PKU). PAH gene mutations were determined in 196 maternal PKU subjects and their offspring. The women were grouped according to PAH genotype, which predicts the metabolic phenotype (severe PKU, mild PKU, and mild hyperphenylalaninemia [MHP]). IQ was determined in both the mothers (Wechsler Adult Intelligence Scale-Revised at >18 years) and their children (Wechsler Intelligence Scale for Children-Revised at > or = 6-7 years of age). According to PAH genotypes, 62% of the women exhibited severe PKU, 19% exhibited mild PKU, and 19% exhibited MHP. Maternal IQ increased, and the assigned phenylalanine (Phe) levels decreased with decreasing severity of PAH genotype. In offspring of mild maternal PKU, multiple regre...
Maternal phenylketonuria collaborative study, obstetric aspects and outcome: The fast 6 years
International Journal of Gynecology & Obstetrics, 1992
OBJECTIVE: The purpose of this study was to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity associated with maternal hyperphenylalaninemia in women of childbearing age with blood phenylalanine levels >240 .... mol/L (>4 mg/dl) on an unrestricted diet. STUDY DESIGN: Two hundred thirteen pregnant women with hyperphenylalaninemia that resulted in 134 live births have been enrolled in the study. Outcome measures were subject to the x 2 test, Fisher exact test, analysis of variance, t test, or Wilcoxon nonparametric test for analysis.