Maternal phenylketonuria: report from the United Kingdom Registry 1978-97

Background: The effects of maternal phenylalanine on the fetus include facial dysmorphism, microcephaly, intrauterine growth retardation, developmental delay, and congenital heart disease. Aims: To evaluate the impact of phenylalanine restricted diet in pregnant women with phenylketonuria (PKU) on their offspring. Methods: Data on virtually all pregnancies of women with PKU in the United Kingdom between 1978 and 1997 were reported to the United Kingdom PKU Registry. The effect of the use and timing in relation to pregnancy of a phenylalanine restricted diet on birth weight, birth head circumference, the presence or absence of congenital heart disease (CHD), 4 year developmental quotient, and 8 year intelligence quotient were examined. Results: A total of 228 pregnancies resulted in live births (seven twin pregnancies were excluded). In 110 (50%), diet started before conception. For this group mean (SD) birth weight was 3160 (612) g, birth head circumference 33.6 (1.9) cm, 4 year DQ 108.9 (13.2), 8 year IQ 103.4 (15.6), and incidence of CHD was 2.4%. In comparison, for those born where treatment was started during pregnancy (n = 91), birth weight was 2818 (711) g, birth head circumference 32.7 (2.0) cm, 4 year DQ 96.8 (15.0), 8 year IQ 86.5 (13.0), and incidence of CHD was 17%. Month-by-month regression analyses suggested that metabolic control by 12–16 weeks gestation had most influence on outcome. Conclusions: Many features of the maternal PKU syndrome are preventable by starting a phenylalanine restricted diet. Women with PKU and their carers must be aware of the risks and should start the diet before conception, or as soon after as possible.     

Congenital heart disease in maternal phenylketonuria: report from the Maternal PKU Collaborative Study

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.     

Maternal phenylketonuria: the French survey

We report the French experience regarding pregnancies in maternal phenylketonuria (PKU). In 2001, a questionnaire was sent to each referring PKU specialist in the 20 centres of each region of France, collecting reports on 135 pregnancies in 79 women born between 1958 and 1980. The majority of the 135 pregnancies occurred after 1990. A total of 42 women were informed of the risks of untreated pregnancy, while 26 were not informed (no data for 11). A strict diet was achieved in 83% of informed and in 16% of uninformed mothers prior to conception. Healthy offspring were observed in 43% of the 135 pregnancies, spontaneous abortions in 10.4%, elective abortions in 4.4%, therapeutic abortions in 12.6%, and embryopathies (EP) in 21.5%. In 8.1% of cases, the outcomes (in earliest pregnancies) are unknown. The proportion of healthy children increased over time and reached 80% of the pregnancies of informed females. There were seven heart defects, all in cases of EP, but although microcephaly and intrauterine growth retardation (IUGR) were almost constant in EP, we also found nine healthy children with IUGR. A continuum between EP and healthy children is suggested. The anthropometric data of the mothers showed that their body mass index (BMI) distribution was shifted to the left compared to women of the general population. This lower BMI and poor weight gain during pregnancy could contribute to the IUGR observed in normal babies whose mothers received a phenylalanine-restricted diet during pregnancy. Conclusion:the information and the preconception diet are effective for avoiding embryopathies in maternal phenylketonuria. Nutritional parameters can influence fetal growth and the nutritional state must be closely monitored throughout pregnancies of women with phenylketonuria.Abbreviations BMI body mass index - EA elective abortion - EP embryopathy - IUGR intrauterine growth retardation - MPKU maternal phenylketonuria - MPKUCS maternal phenylketonuria collaborative study - Phe phenylalanine - PKU phenylketonuria - SA spontaneous abortion - TA therapeutic abortionOn behalf of the PKU workgroup of the Association Française pour le Dépistage et la Prévention des Handicaps de lEnfant (AFDPHE)     

American Academy of Pediatrics: Maternal phenylketonuria

Elevated maternal phenylalanine levels during pregnancy are teratogenic and may result in growth retardation, significant psychomotor handicaps, and birth defects in the offspring of unmonitored and untreated pregnancies. Women of childbearing age with all forms of phenylketonuria, including mild variants such as hyperphenylalaninemia, should receive counseling concerning their risks for adverse fetal effects optimally before conceiving. The best outcomes occur when strict control of maternal phenylalanine levels is achieved before conception and continued throughout the pregnancy.     

Paediatric trauma in Spain: a report from the HUGM Trauma Registry.

OBJECTIVES: To analyse the characteristics of the infant population suffering trauma in our setting. To evaluate the importance of the different aetiological mechanisms. To study the pre- and intra-hospital management of these children. To describe the relative significance of the different lesions. To establish the magnitude of paediatric trauma as a social problem in terms of morbidity and mortality. MATERIAL AND METHODS: From January 1995 to April 2002, a total of 2633 children admitted to our Centre (Hospital Universitario Gregorio Maranon) after suffering some type of injury were included in our Trauma Register. 108 variables have been analysed, including the identification of the patient, type, site and mechanism of the accident, pre-hospital care, transport, complete evaluation on admission, indices of injury severity, diagnostic tests, lesions, treatments performed and morbidity and mortality. RESULTS: The accidents were more frequent in boys than in girls (68.5 % versus 31.5 %). The predominant age group was the 12 - 15 year old group (36.8 %). There was a higher frequency of accidents in the street (37.2 %) than at home (19.4 %) or at school (13.8 %). The most frequent mechanism was a fall (35.6 %), followed by road traffic accidents (23.7 %). On admission, 14.7 % of the children had a Paediatric Trauma Score (P.T.S.) < or = 8 (n = 388). 3.8 % were considered severe multiple trauma patients, presenting an Injury Severity Score (I.S.S.) > or = 15 (n = 101). 4.2 % of the children required intensive care. The most frequent lesions were those of the locomotor system (58.1 %) and head injuries (34.9 %). Some type of surgical or orthopaedic procedure was performed under general anaesthesia in 1522 patients (57.8 %). The mean length of stay was 4.4 days (range 1 - 214 days). Sequelae of some form were detected in 36.4 % of the patients over 3 years of age. The total mortality was 0.5 % (n = 13), being 12.8 % in the group of patients with an I.S.S. > or = 15. CONCLUSIONS: Analysis of the data in our Registry has helped us to define the characteristics of the paediatric trauma population in our setting, to monitor the management of trauma in the different care levels and to develop prevention programmes. It has also enabled us to compare the results with those of other centres in terms of morbidity and mortality with the aim of identifying and correcting any possible deficiencies in the care system.     

Ventilator dependency in the United Kingdom.

There are 24 children who are currently long term ventilator dependent in the UK. Nine of these are cared for entirely at home. An additional 11 children have been long term ventilator dependent since March 1983. The prevalence of these children appears to be increasing. The financial and manpower resources needed for these children whether at home or in hospital is considerable. There are reasons to suppose that the apparent increase in prevalence will continue.     

United Kingdom school-entry hearing screening: current practice.

OBJECTIVE: To determine if the school-entry hearing screening (SEHS) programme continues to make a useful contribution to the identification of childhood hearing impairment in the light of the recent implementation of universal newborn hearing screening, and thereby to inform future policy development. DESIGN: Postal questionnaire survey to determine current implementation and effectiveness of SEHS SETTING: 244 school health services managed within primary care and acute trusts throughout the UK. PARTICIPANTS: 229 SEHS service leads approached; 195 responded. MAIN OUTCOME MEASURE: Details of implementation; positive predictive value of the screening test and its referral criteria. RESULTS: Implementation of the SEHS is variable, and there is no national approach to data collection, audit and quality assurance. Less than 10% of services had available robust data. The yield from screening ranges from 0.05% to 0.59% for permanent sensorineural hearing impairment and from 0.07% to 0.44% for permanent conductive hearing impairment. The positive predictive values from screen referral vary from 0.62% to 12.16% for permanent sensorineural hearing impairment and 1.24% to 17.56% for permanent conductive hearing impairment. CONCLUSION: This comprehensive survey provides a previously unavailable national examination of the SEHS. The few available data on yield indicate that the SEHS may have a small but important role to play in identification of childhood hearing impairment, but the overwhelming conclusion is the urgent need for national guidelines on implementation of this screening programme to determine its value since the implementation nationally of universal newborn hearing screening.     

Maternal phenylketonuria: comparison of two treated full term pregnancies

This case report documents the fetal outcome of two full term pregnancies in a patient with phenylketonuria (PKU). She was treated with a low phenylalanine diet preceeding and during both pregnancies. During her first full term pregnancy she was not able to maintain the rigid diet, and this pregnancy resulted in the delivery of a growth-retarded, microcephalic boy. In her second pregnancy the patient maintained the diet until her delivery at full term. Maternal blood phenylalanine levels remained with two exceptions below 600 mol/l throughout pregnancy and an infant of normal weight and head circumference was born.Abbreviations PKU phenylketonuria - BPD biparietal diameter     

Mortality from early onset group B streptococcal infection in the United Kingdom.

AIMS: To assess the assumption that group B streptococcal infection is less common in the United Kingdom than it is in the United States. METHODS: All stillbirth and neonatal death records in the former Northern Health Region were scrutinised to determine how many babies had died of infection in 1981-96, and what had been the cause. RESULTS: Fifty one of 630 206 live born babies had died of confirmed group B streptococcal infection after becoming symptomatic within 48 hours of birth (0.8 neonatal deaths per 10,000 live births). There were a further 27 deaths from infection without a confirmed microbiological diagnosis, and 17 stillbirths from confirmed group B streptococcal infection. CONCLUSIONS: The incidence of death from early onset infection was marginally higher than the officially estimated rate for the United States before widespread prophylaxis was attempted. Strategies for perinatal prevention deserve greater attention in the United Kingdom.     

Neonatal intensive care provision in the United Kingdom 1992-3

Medical neonatal units in the United Kingdom were surveyed in 1994 to determine for 1992-3 the number of cots, medical and nursing staff, workload, the ability of units to retrieve data and to assess any changes that might have occurred since the NHS reforms. There was an 84% response rate. Many units were unable to provide workload and birthweight specific information. Cot occupancy, and therefore the exposure of individual neonatal nurses to babies requiring intensive care, increased in direct proportion to unit workload. In spite of this a third of all neonatal intensive care, even for babies of <1000 g, is provided by units with ventilator workloads of 50 or fewer babies a year. There was a 25% increase in intensive care level 1 (ICL1) cot provision between 1989 and 1993, but no change in the total number of cots. Consistent maintenance of a common dataset by all units undertaking neonatal intensive care would do much to assist future planning.     

Maternal phenylketonuria. Problems in detecting and risk educating identified females]

Maternal PKU is an embryo-fetopathy caused by elevated plasmaphenylalanine levels in pregnant women with hyperphenylalaninemia and phenylketonuira. Leading symptoms are microcephaly, mental retardatioin and congenital malformations, especially congenital heart disease. Maternal PKU becomes more important since early treated and normally developed girls with PKU are reaching their reproductive age in increasing numbers. There is a lack of adequate knowledge about the dangers of maternal PKU in at-risk women. Only 43% of these women in the Federal Republic of Germany are located by now and can be informed and instructed. Ways and conditions of tracking are described.