MATERNAL PHENYLKETONURIA COLLABORATIVE STUDY (MPKUCS) OFFSPRING - FACIAL ANOMALIES, MALFORMATIONS, AND EARLY NEUROLOGICAL SEQUELAE

Maternal phenylketonuria (PKU) in untreated women has resulted in offs pring with microcephaly, mental retardation, congenital heart disease (CHD), and intrauterine growth retardation. The Maternal Phenylketonur ia Collaborative Study (MPKUCS) was designed to determine the effect o f dietary control of blood phenylalanine (Phe) during pregnancy in pre venting damage to the fetus associated with untreated Maternal PKU. A cohort of offspring hom MPKUS pregnancies was ascertained and examined to evaluate malformations, including CHD, craniofacial abnormalities, microcephaly, intrauterine and postnatal growth retardation, other ma jor and minor defects, and early abnormal neurological signs. For anal ysis, the women were grouped according to their mean Phe levels in mu mol/liter, less than or equal to 360, 361-600, 601-900, or >900, durin g critical gestational weeks of 0-8 (N=203) and 8-12 (N=190), and aver age for Phe exposure throughout pregnancy (N=183). Frequencies of cong enital abnormalities increased with increasing maternal Phe levels. Si gnificant relationships included average Phe 0-8 weeks and CHD (P=0.00 1); average Phe 8-12 weeks and brain, fetal, and postnatal growth reta rdation (P <0.0005 for all), wide nasal bridge (P <0.0005), and anteve rted nares (P=0.001); and average Phe exposure during the entire pregn ancy and neurological signs (P <0.0005). Although 14% of infants had C HD, none of the CHD occurred at 120-360 mu mol/liter and only one (3%) at 361-600 mu mol/liter. At levels of 120-360 mu mol/liter, there wer e three infants (6%) with microcephaly, two (4%) with postnatal growth , and none with intrauterine growth retardation, in contrast to 85%, 5 1%, and 26%, respectively, with Phe above 900 mu mol/liter. These data support the concept that women with PKU should begin a low-phenylalan ine diet to achieve Phe levels of <360 mu mol/liter prior to conceptio n and should maintain this throughout pregnancy. (C) 1997 Wiley-Liss, Inc.