Maternal mild hyperphenylalaninemia: An international survey of offspring outcome

Citations from the literature /International

Journal of Gynecology & Obstetrics 50 (1995) 217-226

SPl increased significantly with gestation and in trisomic fetuses levels of both hormones were reduced. However, discriminant analysis demonstrated that SPI did not contribute significantly in the distinction between trisomic and control pregnancies. Although levels of PAPP-A were reduced throughout the gestational range examined (10 to 13 weeks), especially in caseswith fetal trisomy 21, the deviation was more pronounced at 10 to 11weeks than at 12to 13 weeks gestation. In 45% of pregnancies with fetal trisomy 21 and 70% of pregnancieswith trisomies 18 or 13 maternal serum PAPP-A levels at 10 to 11 weeks gestation were below the 5th centile of the normal range. Conclusion. Maternal serum PAPP-A concentration in the first trimester of pregnancy may prove to be useful in the prediction of risk for fetal trisomies. Maternal serumpregnancy-associatedplasma protein a and fetal nwhal bansloccncy tbickncasfor the prediction of fetal trisomies lo early pregmncy Brizot M.L.; Snijders R.J.M.; Bersinger N.A.; Kuhn P.; Nicolaides K.H. GBR

OBSTET GYNECOL 1994 8416(918-922) Objective: To determine if the risk for fetal trisomies during the first trimester of pregnancy can be derived by combining data from maternal serum pregnancy-associated plasma protein A (PAPP-A) and fetal nuchal translucency thickness. Methods: Pregnancy-associated plasma protein A was measured in samples from 87 singleton pregnancies with fetal chromosomal abnormalities (45 trisomy 21, 19 trisomy 18, eight trisomy 13, 11 sex chromosome aneuploidies, four triploidies) and 348 chromosomally normal controls at IO-13 weeks’ gestation. Likelihood ratios for trisomies 2 1, 18, and 13 in relation to PAPP-A in multiples of the normal median (MOM) for crown-rump length,were derived from the overlapping gaussian frequency distribution curves for normal and abnormal pregnancies. Results: In the chromosomally normal group, maternal serum PAPP-A correlated significantly with fetal crown-rump length (r = 0.421, P < 0.0001). In the chromosomally abnormal group, the median PAPP-A was significantly lower than in the normal controls. The respective median values expressedin MOM for trisomies 21, 18, and 13 and other aneuploidies were 0.5 MOM (90% confidence interval [CI] 0.09-1.67, r = 6.0, P < O.OOl), 0.17 MOM (90% CI 0.06-1.45, z = 6.6, P < O.OOl),0.25 MOM (90% CI 0.10-0.62 z=4.5, P < 0.OOl),and0.72MoM(9O%CI0.09-2.48,z=2.2, P < 0.05), respectively. There was no significant linear association between PAPP-A and fetal nuchal translucency thickness in either the chromosomally normal (r = -/O/.01,P = 0.89) or abnormal groups (r = -0.19, P = 0.08). Conclusion: The risks for fetal trisomies at IO- 13 weeks’ gestation can be derived by combining data on maternal age, maternal serum PAPP-A, and fetal nuchal translucency thickness. Maternal mild I~yperpbenylalPniwmia: An intematiod survey of offspring outcome Levy H.L.; Waisbren S.E.; Lobbregt D.; Allred E.; Schuler A.; Trefz F.K.; Schweitzer S.M.; Sardharwalla LB.; Walter J.H.; Barwell B.E.; Berlin C.M. Jr.; Leviton A.; Andrews B.; Kinkus

225

K.; Aoki K.; Berlow S.; Van Calcar S.; Breck J.; Sundquist W.; et al. USA

LANCET 1994344/8937(1589- 1594) Maternal phenylketonuria (PKU) has adverse effects on the offspring including microcephaly, mental retardation, congenital heart disease,and intrauterine growth retardation. Maternal non-PKU mild hyperphenylalaninemia (MHP) is believed to be benign, but whether there may be long-term consequencesto offspring is unclear. In an international survey we have obtained information about 86 mothers with MHP (blood phenylalanine 167-715 mol/L), their 219 untreated pregnancies, and 173 offspring. Spontaneous fetal loss (13% of pregnancies), congenital heart disease (2.3% of offspring), and severe non-cardiac anomalies (2.9% of offspring) occurred at frequencies within expected limits for the general population. For weight and length at birth the median percentile was the 50th but that for birth head circumferencewas the 25th. Median z-scores for birth length and head circumference were significantly lower for offspring of mothers with phenylalanine concentrations above 400 mol/l than for those whose mothers had lower values (p = 0.05 and p = 0.005,respectively). The median intelligence quotient (IQ) of the offspring (3-27 years) was 100for those whose mothers had higher phenylalanine concentrations and 108 for those of the lower phenylalaninemia group. However, offspring IQ correlated slightly more closely with maternal IQ (r = 0.53,p < 0.001)than with maternal phenylalanine concentration (r = 0.45, p = 0.02). Maternal MHP doesnot seemto have seriousconsequencesfor the fetus. A maternal phenylalanine concentration of lessthan 400 pmohl does not warrant intervention. Nevertheless,maternal blood phenylalanine above this value is associatedwith slightly lower birth measurementsand offspring IQ than lower maternal blood phenylalanine concentrations. Acute fatty liver of pregnancy:An experiencein the diagnosisand managementof fourteen cases Usta I.M.; Barton J.R.; Amon E.A.; Gonzalez A.; Sibai B.M. USA

AM J OBSTET GYNECOL 1994 171/5(1342-1347) Objective: Our purpose was to investigate the diagnostic problems and maternal-p&natal outcome in casesof acute fatty liver of pregnancy. Study design: Fourteen cases with acute fatty liver of pregnancy managed during the past I-years were studied with emphasison presenting symptoms, admitting diagnosis, laboratory findings, clinical course, maternal complications, and neonatal outcome. Results: The mean gestational age at onset was 34.5 weeks (range 28 to 39). Only seven patients had acute fatty liver of pregnancy as a definite or suspecteddiagnosis on admission.-Computed tomography of the liver was performed on 10 patients, with only two positive results. There were no maternal deaths; however, maternal morbidity was frequent: four patients had hepatic encephalopathy, three pulmonary edema, three ascites, four respiratory arrest, two diabetes insipidus, and 10 had transfusion of blood or blood products to correct either disseminated intravascular coagulation or excessive bleeding. Coagulation