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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The maternal phenylketonuria (PKU) syndrome refers to the teratogenic effects of PKU during pregnancy. These effects include mental retardation, microcephaly, congenital heart disease, and intrauterine growth retardation. In untreated pregnancies wherein the mother has classic PKU with a blood phenylalanine level > or = 1,200 microM (20 mg/dl), the frequencies of these abnormalities in offspring are exceedingly high, approaching 75-90% for microcephaly and mental retardation and 15% for congenital heart disease. There is a dose response relationship with progressively lower frequencies of these abnormalities at lower phenylalanine levels, both in the pregnancies of women with variants of PKU and in treated classic PKU pregnancies. The pathogenesis of this syndrome is unknown; it may be related to inhibition by phenylalanine of large neutral amino acid transport across the placenta or to direct toxicity of phenylalanine and/or a phenylalanine metabolite in certain fetal organs. A mouse model for PKU now exists, and studies of maternal PKU in this model are in progress. The treatment of maternal PKU consists of biochemical control through a phenylalanine restricted diet during pregnancy. The best results are obtained with diet initiation before conception or no later than the earliest weeks of pregnancy. Women with PKU and their families require much psychosocial support to meet the strict requirements of a maternal PKU pregnancy, including compliance with a difficult diet. With such compliance, however, it seems that bearing normal or near normal offspring is possible.
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PMID:Maternal phenylketonuria: a metabolic teratogen. 876 85

The reproductive effects of metabolic disorders in women can be divided into four categories. The first of these is infertility. Galactosemia with its complication of ovarian failure is the disorder in this category. This complication may be prenatal in origin but whether this is so and its cause are unknown. The second category includes pregnancy effects of maternal metabolic disorders. The urea cycle disorder ornithine transcarbamylase (OTC) deficiency, maternal maple syrup urine disease and maternal homocystinuria are in this category. In the first two disorders, postpartum life-threatening illness due to metabolic crisis has occurred. Maternal homocystinuria is associated with a high risk for postpartum thromboembolic complications. The third category is the pregnancy effect of a fetal metabolic disorder. Pregnancies in which the fetus had long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) have been complicated by the life-threatening (HELLP) syndrome during the third trimester. Rapid recovery of the mothers followed delivery, on occasion by emergency cesarean section. The fourth category is the fetal effects (teratogenicity) from a maternal metabolic disorder. The best-known example of this is maternal phenylketonuria (PKU), which produces microcephaly, mental retardation, congenital heart disease and intrauterine growth retardation. Treatment with a low phenylalanine diet begun before conception or no later than the earliest weeks of the first trimester markedly reduces the risk to the fetus and can result in normal offspring. Other examples of teratogenicity may include maternal homocystinuria and maternal hypothyroidism.
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PMID:Reproductive effects of maternal metabolic disorders: implications for pediatrics and obstetrics. 882 3

It is well established that women with phenylketonuria who remain untreated during pregnancy face serious problems in offspring outcome. Surveys have documented that maternal phenylalanine (Phe) blood concentrations above 1200 mumol/l are associated with microcephaly, congenital heart disease and intrauterine growth retardation among their offspring. To investigate the efficacy of the Phe restricted diet, the National Institute of Child Health and Human Development in Bethesda Maryland developed an international study to evaluate fetal outcome in pregnancies treated with the Phe restricted diet. The study involves over 100 metabolic clinics in the United States, Canada and Germany, and is now in its 10th year. The results included in this report are still preliminary in nature and the actual risk for such pregnancies remains to be determined.
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PMID:Outcome implications of the International Maternal Phenylketonuria Collaborative Study (MPKUCS): 1994. 882 36

By November 1994, 39 pregnancies had been completed in phenylketonuric mothers. Dietary control was post-conception in 6 and 2 of these offspring died of congenital heart disease and 1 other needed surgery for coarctation. There were no heart defects in the 34 offspring of the 33 pregnancies following preconception diet controlled by Guthrie assays of maternal phenylalanine three (Phe) weekly. These Phe results were analysed by trimester for the means, the number of days over 300 mumol/l or below 60 mumol/l. Generally good control was achieved suggesting the UK guidelines drawn up by the MRC Working Party are broadly achievable but excessively high and low values occur intermittently in many pregnancies both of which may adversely affect the fetus. Though developmental assessment scores at 1 year were over 100 in all but five, early outcome results suggest that intellectual development may still be impaired at 4 years. Until much more information is available caution is still needed in discussing outcome with phenylketonuria patients who wish to conceive.
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PMID:Maternal phenylketonuria. A study from the United Kingdom. 882 40

Maternal phenylketonuria (PKU) is teratogenic and results in birth defects that include microcephaly, mental retardation, congenital heart disease, and intrauterine growth retardation. Treatment with a low phenylalanine diet can prevent or reduce the severity of the complications. Optimal benefit, however, requires frequent monitoring with fetal ultrasonography as a critical element. We have studied ultrasonography in 39 pregnancies enrolled in the Maternal PKU Collaborative Study and followed at our centre. First-trimester examinations in 24 pregnancies resulted in the discovery of non-viability in five. In each, this led to discontinuation of the difficult and expensive diet. Among the 33 pregnancies with second-trimester evaluation, congenital heart disease was identified in five. Two of these pregnancies were terminated. Microcephaly as determined by biparietal diameter (BPD) was identified in the second trimester in only one of nine fetuses who had microcephaly at birth. Among 20 pregnancies with third-trimester ultrasound, fetal microcephaly was identified by BPD in three of seven who had birth microcephaly. We conclude that fetal ultrasonography in maternal PKU is valuable during the first trimester in identifying non-viable pregnancies and determining gestational age and is also valuable during the second trimester in identifying congenital heart disease and perhaps other major anomalies, but not in identifying fetal microcephaly. Third-trimester ultrasound seems to be of limited usefulness.
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PMID:Fetal ultrasonography in maternal PKU. 884 68

Maternal phenylketonuria (PKU) in untreated women has resulted in offspring with microcephaly, mental retardation, congenital heart disease (CHD), and intrauterine growth retardation. The Maternal Phenylketonuria Collaborative Study (MPKUCS) was designed to determine the effect of dietary control of blood phenylalanine (Phe) during pregnancy in preventing damage to the fetus associated with untreated Maternal PKU. A cohort of offspring from MPKUS pregnancies was ascertained and examined to evaluate malformations, including CHD, craniofacial abnormalities, microcephaly, intrauterine and postnatal growth retardation, other major and minor defects, and early abnormal neurological signs. For analysis, the women were grouped according to their mean Phe levels in mumol/liter, < or = 360, 361-600, 601-900, or > 900, during critical gestational weeks of 0-8 (N = 203) and 8-12 (N = 190), and average for Phe exposure throughout pregnancy (N = 183). Frequencies of congenital abnormalities increased with increasing maternal Phe levels. Significant relationships included average Phe 0-8 weeks and CHD (P = 0.001); average Phe 8-12 weeks and brain, fetal, and postnatal growth retardation (P < 0.0005 for all), wide nasal bridge (P < 0.0005), and anteverted nares (P = 0.001); and average Phe exposure during the entire pregnancy and neurological signs (P < 0.0005). Although 14% of infants had CHD, none of the CHD occurred at 120-360 mumol/liter and only one (3%) at 361-600 mumol/liter. At levels of 120-360 mumol/liter, there were three infants (6%) with microcephaly, two (4%) with postnatal growth, and none with intrauterine growth retardation, in contrast to 85%, 51%, and 26%, respectively, with Phe above 900 mumol/liter. These data support the concept that women with PKU should begin a low-phenylalanine diet to achieve Phe levels of < 360 mumol/liter prior to conception and should maintain this throughout pregnancy.
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PMID:Maternal Phenylketonuria Collaborative Study (MPKUCS) offspring: facial anomalies, malformations, and early neurological sequelae. 906 90

Baroreflex sensitivity (BRS) conveys useful prognostic information in patients with heart disease, yet methods for its quantification suffer from poor reproducibility and test failure in some patients with heart failure. We set out to compare the short-term reproducibility and success rate of four different methods of assessing BRS in normal subjects and patients with chronic heart failure (CHF). A total of 31 patients with CHF and 18 normal controls underwent BRS testing using four techniques: (1) bolus phenylephrine (BRS(Phe)), (2) alpha-index in both low- and high-frequency bands (BRS(alphaLF) and BRS(alphaHF) respectively), (3) the sequence method (BRS(Seq)), and (4) a new 0.1 Hz controlled-breathing, time-domain analysis method (BRS(Cbr)). Each subject underwent two test episodes with each method on the same day. The average values for BRS in patients and controls respectively were: BRS(Phe), 4.4 (+/-4.4) ms/mmHg and 19.8 (+/-11.5) ms/mmHg; BRS(alphaLF), 5.6 (+/-4.1) ms/mmHg and 15.4 (+/-5.0) ms/mmHg; BRS(alphaHF), 7.1 (+/-7.0) ms/mmHg and 25.1 (+/-8.3) ms/mmHg; BRS(Seq), 7.7 (+/-6.3) ms/mmHg and 22.5 (+/-8.4) ms/mmHg; BRS(Cbr), 6.6 (+/-5.9) ms/mmHg and 22.8 (+/-10.8) ms/mmHg. The coefficients of variation (S.D. of the difference in repeated values divided by mean) in patients and controls respectively were: BRS(Phe), 85.6% and 52.2%; BRS(alphaLF), 65.9% and 33.7%; BRS(alphaHF), 99.7% and 52. 1%; BRS(Seq), 30.7% and 40.4%; BRS(Cbr), 30.7% and 19.6%. The numbers of test failures in patients were: BRS(Phen), 15; BRS(alphaLF), 7; BRS(alphaHF), 5; BRS(Seq), 14; BRS(Cbr), 1. Of the four techniques assessed for measuring BRS, the controlled breathing time-domain method yielded the best reproducibility and lowest failure rate in controls and in patients with CHF.
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PMID:Reproducibility of methods for assessing baroreflex sensitivity in normal controls and in patients with chronic heart failure. 1049 52

Phenylketonuria in pregnancy carries with it an increased risk of spontaneous abortion and development of a fetus that is affected by the maternal phenylketonuria syndrome. This syndrome is characterized by low birthweight, congenital heart disease, microcephaly, childhood growth failure, and cognitive impairment. It is the result of the hyperphenylalaninemia that accompanies the phenylketonuric state, and may therefore be avoided by maintaining maternal serum phenylalanine levels within the normal range. Phenylalanine is an essential amino acid and may be controlled by dietary manipulation. Presented here is a case history of a woman with phenylketonuria who was unable to satisfactorily control her serum phenylalanine levels in each of her three pregnancies. All three children were adversely affected by the fetopathy of the maternal phenylketonuria syndrome, each with evidence of growth failure and impaired neurodevelopment. This patient illustrates the difficulties that may be encountered when providing obstetric care to the woman with phenylketonuria who is not able or not willing to restrict her dietary intake of phenylalanine. The discussion includes consideration of management strategies, including dietary therapy and legal intervention.
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PMID:Repeated adverse fetal outcome in pregnancy complicated by uncontrolled maternal phenylketonuria. 1057 68

Maternal phenylketonuria (PKU) syndrome results in multiple congenital anomalies in the offspring, usually consisting of microcephaly, intrauterine growth retardation, dysmorphology, and congenital heart disease. Pregnancies treated preconceptionally with a phenylalanine-restricted diet and control of maternal blood phenylalanine levels within the recommended range result in normal offspring. However, in this 15-year study, several significant factors resulted in microcephaly in 27% of the offspring, and 7% exhibited serious congenital heart disease. These results occurred chiefly in women with mean IQ scores of 83 associated with low socioeconomic status and decreased educational achievement. Another important factor associated with suboptimal control of blood phenylalanine levels during pregnancy was the fact that most pregnancies were not carefully planned and occurred in women off dietary treatment with phenylalanine-restricted products. These results indicate that greater effort must be developed to assist women with PKU in remaining on diet during their reproductive years. It appears that continued adherence to the diet, resulting in normal maternal intelligence, is an important contribution to improved fetal development.
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PMID:Maternal phenylketonuria: an international study. 1100 15

The frequency and types of congenital heart disease in offspring from pregnancies in women with hyperphenylalaninemia were examined in the international prospective Maternal Phenylketonuria Collaborative Study. Relationships of congenital heart disease in offspring to the basal blood phenylalanine level in the mother, metabolic control through diet during pregnancy, and phenylalanine hydroxylase mutations in mother and offspring were determined. The 416 offspring from 412 maternal phenylketonuria pregnancies that produced live births and 100 offspring from the 99 control pregnancies were included in this examination. Thirty-four of the 235 offspring (14%; 95% CI, 10.2 to 19.6%) from pregnancies in phenylketonuric women with a basal phenylalanine level > or = 900 microM (15 mg/dL) [normal blood phenylalanine < 120 microM (2 mg/dL)] and not in metabolic control [phenylalanine level < or = 600 microM (10 mg/dL)] by the eighth gestational week had congenital heart disease compared with one control offspring (1%) with congenital heart disease. One offspring among the 50 (2%) from mothers with non-phenylketonuria mild hyperphenylalaninemia also had congenital heart disease. Coarctation of the aorta and hypoplastic left heart syndrome were overrepresented compared with expected percentages among those with congenital heart disease in the general population. A basal maternal phenylalanine level > 1800 microM (30 mg/dL) significantly increased the risk for bearing a child with congenital heart disease (p = 0.003). Phenylalanine hydroxylase mutations in the mothers and offspring did not have an independent relationship to congenital heart disease but were related through the basal maternal phenylalanine levels. The data in this study indicate that a basal maternal phenylalanine level of 900 microM may be a threshold for congenital heart disease, that women with the most severe degree of phenylketonuria are at highest risk for bearing such a child, and that prevention of the congenital heart disease requires initiation of the low phenylalanine diet before conception or early in pregnancy with metabolic control no later than the eighth gestational week.
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PMID:Congenital heart disease in maternal phenylketonuria: report from the Maternal PKU Collaborative Study. 1132 45


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