The international collaborative study of maternal phenylketonuria: status report 1994

Neonatal screening for phenylketonuria (PKU) has created a problem as females with PKU are reaching child-bearing age. Surveys have revealed that maternal phenylalanine blood concentrations greater than 1200 μmol/l are associated with fetal microcephaly, congenital heart defects and intrauterine growth retardation. It is estimated that as many as 3000 hyperphenylalaninemic females may be at risk of producing these fetal abnormalities. To examine this problem, the international maternal PKU collaborative study was developed to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity. Preliminary findings have indicated that phenylalanine restriction should begin before conception for females with PKU planning a pregnancy. Dietary control should maintain maternal blood phenylalanine levels between 120 and 360 μmol/l and should provide adequate energy, protein, vitamin and mineral intake. Pregnant hyperphenylalaninemic females who achieved metabolic control after conception or by the 10th week of pregnancy had a better offspring outcome than anticipated. The results of 402 pregnancies are reviewed.     

Regional myocardial dysfunction: evaluation of patients with prior myocardial infarction with fast CT

A prototype ultrafast cine computed tomographic (CT) scanner, designed specifically for cardiac imaging, was used to evaluate a preliminary series of patients with prior myocardial infarction (n = 21) and a control group without coronary artery disease (n = 5). Multilevel 50-msec CT scan exposures were obtained during peripheral intravenous bolus injections of contrast medium. A comparison was made between cine-CT scans and standard left ventriculographic images in assessing segmental left ventricular motion. Results indicate that cine CT, performed at sufficiently rapid speeds (20 scans per second) to allow useful analysis of regional ventricular wall motion, can provide adequate image quality. Analysis of 110 segments revealed a good correlation (90.9%) between the two techniques in characterizing normal from abnormal regional wall motion. Cine CT, based on this initial study, demonstrates considerable potential for evaluating not only cardiac chamber dimensions but also segmental wall dynamics.     

Methodologic and logistic issues in conducting longitudinal birth cohort studies: lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research

In anticipation of the National Children's Study, lessons can be learned from the smaller birth cohort studies conducted by five Centers for Children's Environmental Health and Disease Prevention Research funded by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency. The populations studied are diverse in ethnicity and social class and reside in urban and rural environments. Although almost all of the centers chose to enroll participants through medical care facilities, they had to develop independent staffs and structures because of the overburdened medical care system. Some of the lessons learned by the centers include the importance of continuous funding, building community partnerships to conduct culturally appropriate research, hiring bilingual and bicultural staff from the community, prioritizing research goals, developing biorepositories to ensure future utility of samples, instituting quality control procedures for all aspects of specimen and data collection, maintaining frequent contact with study participants, ensuring ethical conduct of the research in a changing medical-legal climate, and communicating results in a timely and appropriate manner to participants and the wider community. All centers underestimated the necessary start-up time, staff, and costs in conducting these birth cohort studies. Despite the logistical complexity and added expenses, all centers emphasize the importance of studying the impact of environmental exposures on those children most at risk, those living in minority and low-income communities. These centers present barriers encountered, solutions found, and considerations for future research, with the hope that the lessons learned can help inform the planning and conduct of the National Children's Study.     

Principles and practices of neurodevelopmental assessment in children: lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research

Principles and practices of pediatric neurotoxicology are reviewed here with the purpose of guiding the design and execution of the planned National Children's Study. The developing human central nervous system is the target organ most vulnerable to environmental chemicals. An investigation of the effects of environmental exposures on child development is a complex endeavor that requires consideration of numerous critical factors pertinent to a study's concept, design, and execution. These include the timing of neurodevelopmental assessment, matters of biologic plausibility, site, child and population factors, data quality assurance and control, the selection of appropriate domains and measures of neurobehavior, and data safety and monitoring. Here we summarize instruments for the assessment of the neonate, infant, and child that are being employed in the Centers for Children's Environmental Health and Disease Prevention Research, sponsored by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency, discuss neural and neurobiologic measures of development, and consider the promises of gene-environment studies. The vulnerability of the human central nervous system to environmental chemicals has been well established, but the contribution these exposures may make to problems such as attention deficit disorder, conduct problems, pervasive developmental disorder, or autism spectrum disorder remain uncertain. Large-scale studies such as the National Children's Study may provide some important clues. The human neurodevelopmental phenotype will be most clearly represented in models that include environmental chemical exposures, the social milieu, and complex human genetic characteristics that we are just beginning to understand.     

Antibiotic-laden cement: technique for uniform manual mixing

The use of polymethyl methacrylate has revolutionized surgical technique in total joint arthroplasty. In addition, in an effort to reduce the rate of infections as well as to treat active infections, the practice of adding powdered antibiotics to the cement has become commonplace. A simple and efficient technique of mixing antibiotic powder into cement that creates a uniform distribution of antibiotic is introduced. In addition, this process reduces the presence of "antibiotic voids," which, if present can alter the physical properties of the cement itself.     

Prenatal insecticide exposures and birth weight and length among an urban minority cohort

We reported previously that insecticide exposures were widespread among minority women in New York City during pregnancy and that levels of the organophosphate chlorpyrifos in umbilical cord plasma were inversely associated with birth weight and length. Here we expand analyses to include additional insecticides (the organophosphate diazinon and the carbamate propoxur), a larger sample size (n = 314 mother-newborn pairs), and insecticide measurements in maternal personal air during pregnancy as well as in umbilical cord plasma at delivery. Controlling for potential confounders, we found no association between maternal personal air insecticide levels and birth weight, length, or head circumference. For each log unit increase in cord plasma chlorpyrifos levels, birth weight decreased by 42.6 g [95% confidence interval (CI), -81.8 to -3.8, p = 0.03] and birth length decreased by 0.24 cm (95% CI, -0.47 to -0.01, p = 0.04). Combined measures of (ln)cord plasma chlorpyrifos and diazinon (adjusted for relative potency) were also inversely associated with birth weight and length (p < 0.05). Birth weight averaged 186.3 g less (95% CI, -375.2 to -45.5) among newborns with the highest compared with lowest 26% of exposure levels (p = 0.01). Further, the associations between birth weight and length and cord plasma chlorpyrifos and diazinon were highly significant (p < or = 0.007) among newborns born before the 2000-2001 U.S. Environmental Protection Agency's regulatory actions to phase out residential use of these insecticides. Among newborns born after January 2001, exposure levels were substantially lower, and no association with fetal growth was apparent (p > 0.8). The propoxur metabolite 2-isopropoxyphenol in cord plasma was inversely associated with birth length, a finding of borderline significance (p = 0.05) after controlling for chlorpyrifos and diazinon. Results indicate that prenatal chlorpyrifos exposures have impaired fetal growth among this minority cohort and that diazinon exposures may have contributed to the effects. Findings support recent regulatory action to phase out residential uses of the insecticides.     

Increased responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis to stress in newborns with atopic disposition

In previous studies, atopic patients showed attenuated cortisol responses to psychosocial stress which is suggestive of a hyporeactive hypothalamus-pituitary-adrenal (HPA) axis in this patient group. Regarding the anti-inflammatory role of glucocorticoids, reduced responsiveness of the HPA axis under stress may be one potential explanation of stress-induced exacerbation of atopic symptoms. The present study evaluated whether hyporeactivity of the HPA axis is a feature related to the disposition of atopy rather than a consequence of an ongoing chronic allergic inflammatory process. Newborns with an atopic disposition (parental atopy; n=31) and without atopic disposition (no parental atopy; n=20) were recruited. To further assess atopic disposition, total IgE levels were determined in the cord blood of the neonates. Three days after birth, a blood sample was obtained by a heel prick which is part of a standard pediatric examination. Blood sampling by heel prick is well known to be a significant stressor resulting in activation of the HPA axis in newborns. Analysis of salivary cortisol indicated a significant increase of cortisol levels in the newborns after the stressor with a trend towards an elevated cortisol response in babies with a family history of atopy or with elevated levels of cord IgE (> or = 0.5 kU/l). Neonates with a positive parental atopic heritage and elevated cord IgE were found to show significantly elevated cortisol responses to the heel prick stress when compared to newborns without a parental atopic history and normal cord IgE values. Moreover, cord IgE levels were significantly correlated with basal cortisol levels and the cortisol response to the stressor. These findings suggest that atopic disposition in neonates is associated with altered responsiveness of the HPA axis to stress which may increase the vulnerability to develop manifestation of atopy in later life.     

Aktueller Stand der Jodversorgung bei Erlanger Schulanfängern

Background.

The increased use of iodized salt in foodstuffs and in private households is assumed to improve the iodine supply. But so far large regional differences have been found. Iodine status was determined as part of the FIT (Family-Intervention Trial) study Erlangen evaluating the nutritional status and health of a large cohort of primary school children and parents.

Methods.

Urinary iodine excretion, serum fT4 and TSH of first-grade pupils of the school year 1997/98 in 16 schools in Erlangen (n=168, aged 6–7 years) and their parents (n=251) were examined.

Results.

The median iodine excretion of all the children was 11.1 µg/dl or 106.3 µg/g creatinine. Iodine excretion decreased with increasing age. For adults, the median was 8.3 mg/dl or 68 µg/g creatinine. 53% children, but only 22% adults had an iodine excretion above the WHO recommended level of 100 µg/g creatinine. 2.8% pupils and 0.8% parents had a latent hypothyroidism. The iodine excretion and increased serum TSH-values showed a significant inverse correlation (r=–0.83, p=0.005).

Conclusion.

The iodine status in Erlangen in the study group has improved compared to data obtained in the 1980 s. 45% of children and 80% of adults have an iodine urine concentration below the recommended level. Further efforts are necessary to improve the iodine intake.