Characterization of fetal exposure to multiple metals among an urban population: A case study of New York City.

INTRODUCTION: Metals and metalloids are ubiquitous and persistent in urban areas and are generally released into the environment as mixtures. OBJECTIVES: The purpose of this study was to establish baseline concentrations of selected elements in meconium samples among a large urban population in the US and understand the spatial variability in concentrations. The association of metal mixtures on birth weight was also assessed. METHODS: This cross-sectional study was conducted across five public hospitals located in New York City, NY (NYC) in four boroughs. We collected meconium sample from 116 infants during the first 24 h after delivery and quantified 11 metals using ICP-MS. Principal component analysis was used to determine metal mixtures and their association with birth weight. Spatial hot spots of each metal were calculated using the Getis-Ord (GI*). RESULTS: Essential elements were detected in all samples with Zn in the greatest abundance (median = 274.5 µg/g) and Mo in the least (median = 0.1845 µg/g). Pb was detected in all but two samples (median = 0.0222 µg/g), while Cd levels were detected in approximately half of the samples (median = 0.0019 µg/g). Co-located hot spots were detected for Cu, Zn, and Fe in southeast Brooklyn; Cd, Cr, and Ni in eastern Queens; and Al and Mo in south Queens. There was a significant inverse relationship between Pb concentrations (beta = -1935.7; p = 0.006) and the mixture of Cr, Cu, Mo, Zn (beta = -157.7; p = 0.045) and birth weight. CONCLUSIONS: Our findings indicate that meconium is an effective biomarker for measuring metal exposures among an urban population. We were able to quantify detectable levels of ten of the eleven metals measured in the study and characterize nutritionally necessary trace elements and metals derived from anthropogenic sources without biologic need in a cohort of NYC newborns. Further research needs to establish the change point from necessary to toxic, for the essential elements.

Cranial irradiation in childhood mimicking neurofibromatosis type II.

Neurofibromatosis type II (NF2) is a genetic disease characterized by bilateral vestibular schwannomas (VS) and other nerve system tumors. However, such tumors may be associated with environmental, rather than a genetic, etiology. Individuals fulfilling the clinical criteria of NF2 who had been treated by head ionized irradiation at a young age were compared for disease characteristics and molecular analysis with non-irradiated sporadic NF2 cases. In the study cohort, three of 33 sporadic adult cases fulfilling NF2 diagnostic criteria had a history of early age cranial irradiation exposure. None of the irradiated patients had bilateral VS compared with 73.3% of the non-irradiated individuals. One of the irradiated patients had no VS, while none of the non-irradiated NF2 cases had absence of VS. All of the irradiated individuals had brain meningiomas and thyroid tumors compared with 47% and 0%, respectively, of the non-irradiated individuals. Molecular analyses for NF2 mutations in blood of the irradiated individuals failed to detect disease-causing mutations. This study suggest that environmental factors may mimic NF2. Identifying such non-genetic cases fulfilling clinical criteria of the genetic disease may be crucial for the purposes of genetic counseling and patient management.

Predicting neurofibromatosis type 1 risk among children with isolated café-au-lait macules.

BACKGROUND: Although isolated cafe-au-lait macules (CALMs) are a common skin finding, they are an early feature of neurofibromatosis type 1 (NF1). OBJECTIVE: We sought to develop an algorithm determining the risk of children with CALMs to have constitutional NF1. METHODS: We conducted a retrospective study of patients with isolated CALMs. Diagnosis of NF1 was based on detecting NF1 mutation in blood or fulfilling clinical criteria. RESULTS: In all, 170 of 419 (41%) and 21 of 86 (24%) children with isolated CALMs who underwent molecular testing and clinical follow-up, respectively, were given a diagnosis of NF1. Presence of fewer than 6 CALMs at presentation or atypical CALMs was associated with not having NF1 (P < .001). An algorithm based on age, CALMs number, and presence of atypical macules predicted NF1 in both cohorts. According to the algorithm, children older than 29 months with at least 1 atypical CALM or less than 6 CALMs have a 0.9% (95% confidence interval 0%-2.6%) risk for constitutional NF1 whereas children younger than 29 months with 6 or more CALMs have a high risk (80.4%, 95% confidence interval 74.6%-86.2%). LIMITATIONS: The study was designed to detect constitutional NF1 and not NF1 in mosaic form. CONCLUSIONS: A simple algorithm enables categorization of children with isolated CALMs as being at low or high risk for having NF1.

The effect of parental age on the presence of de novo mutations - Lessons from neurofibromatosis type I.

BACKGROUND: Neurofibromatosis type 1 (NF1) is the most common autosomal dominant neurocutaneous disease with a prevalence of 1:2500. Approximately, 50% of the cases are sporadic. Advanced paternal age is associated with germline mutations and autosomal diseases. We aimed to use NF1 as a paradigm to study the effect of parental age on sporadic mutation rates for both advanced and younger parental ages. METHODS: The medical charts of 118 NF1 pediatric patients followed in a specialized Israeli NF1 clinic were evaluated. Thirty-one cases were diagnosed by genetic tests and 87 by NIH clinical criteria. Sixty-four cases (54%) had a negative family history of NF1 (sporadic cases). Data on parental ages at the time of the children's birth were compared to the national population database. RESULTS: Parental age of children with sporadic NF1 was higher than the general population (32.7 years vs. 30.1 years, respectively, for the mothers and 36.5 years vs. 32.6 years, respectively, for the fathers; P < 0.0001 for both groups). In contrast, the age of the mothers and the fathers in the familial cases (30.3 and 33.9 years, respectively) did not differ from the general population. Significantly, fewer fathers of the sporadic group had been 25-29 years old at their child's birth compared with fathers in the general population (7.8% vs. 21%, respectively, P = 0.009), and significantly more fathers were ≥40 years old (29.7% vs. 13.6%, respectively, P = 0.0002). Differences in maternal age between these two groups were less prominent. CONCLUSION: Parents of sporadic NF1 cases are older. The risk for sporadic NF1 was lower when the fathers were younger at the time of the affected child's birth, and gradually increased with paternal age.

High prevalence of elevated blood pressure among children with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common neurocutaneous disease characterized by café-au-lait spots, axillary and inguinal freckling, neurofibromas, and optic gliomas. Increased rates of hypertension (HTN) were reported among NF1 patients, however, the prevalence of HTN and pre-HTN in pediatric NF1 patients has not been clarified. METHODS: Blood pressure (BP) measurements, weight, and renal ultrasound were assessed in 224 NF1 pediatric patients followed in a specialized NF1 clinic. RESULTS: The cohort's mean age was 9.1 ± 4.1 years. Overweight and obesity were found in 12.9 and 10.3 % of them, respectively. BP was measured averagely 2.9 times per patient on different occasions. Blood pressure was in the pre-HTN and HTN ranges in 14.9 and 16.9 % of measurements, respectively. BP >95th was detected in 20.5 % at the first measurement. Of 114 children with at least three BP measurements, 18.4 % had two values in the HTN range and 6.14 % had at least three. Overweight was not associated with HTN among children with NF1. Urinary tract ultrasonographic abnormalities were detected in 6.8 % (11/161) of cases. CONCLUSIONS: The prevalence of increased BP in pediatric NF1 is much higher than in the general pediatric population. BP has to be regularly assessed and managed in this high-risk population.