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Child blood lead concentrations have been associated with measures of immune dysregulation in nationally representative study samples. However, response to vaccination-often considered the gold standard in immunotoxicity testing-has not been examined in relation to typical background lead concentrations common among U.S. children. The present study estimated the association between blood lead concentrations and antigen-specific antibody levels to measles, mumps, and rubella in a nationally representative sample of 7005 U.S. children aged 6-17 years. Data from the 1999-2004 cycles of the National Health and Nutrition Examination Survey (NHANES) were used. In the adjusted models, children with blood lead concentrations between 1 and 5 µg/dL had an 11% lower anti-measles (95% CI: -16, -5) and a 6% lower anti-mumps antibody level (95% CI: -11, -2) compared to children with blood lead concentrations <1 µg/dL. The odds of a seronegative anti-measles antibody level was approximately two-fold greater for children with blood lead concentrations between 1 and 5 µg/dL compared to children with blood lead concentrations <1 µg/dL (OR = 2.0, 95% CI: 1.4, 3.1). The adverse associations observed in the present study provide further evidence of potential immunosuppression at blood lead concentrations <5 µg/dL, the present Centers for Disease Control and Prevention action level.

Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment Study recruited healthy pregnant women from academic medical centers in four US cities. Gold standard liquid chromatography-tandem mass spectrometry was used to measure maternal sex steroids concentrations (total testosterone [TT], free testosterone [FT], estrone [E1], estradiol [E2], and estriol [E3] concentrations) in serum samples from 548 women carrying singletons (median = 11.7 weeks gestation). Women completed questionnaires on demographic and lifestyle characteristics. Results In multivariable linear regression analyses, hormone concentrations varied in relation to maternal age, body mass index (BMI), race, and parity. Older mothers had significantly lower levels of most hormones; for every year increase in maternal age, there was a 1-2% decrease in E1, E2, TT, and FT. By contrast, each unit increase in maternal BMI was associated 1-2% lower estrogen (E1, E2, E3) levels, but 1-2% higher androgen (TT, FT) concentrations. Hormone concentrations were 4-18% lower among parous women, and for each year elapsed since last birth, TT and FT were 1-2% higher (no difference in estrogens). Androgen concentrations were 18-30% higher among Black women compared to women of other races. Fetal sex, maternal stress, and lifestyle factors (including alcohol and tobacco use) were not related to maternal steroid concentrations. Conclusions for Practice Maternal demographic factors predict sex steroid hormone concentrations during pregnancy, which is important given increasing evidence that the prenatal endocrine environment shapes future risk of chronic disease for both mother and offspring.

Rationale: Fine particulate matter air pollution of 2.5 μm or less in diameter (PM 2.5 ) has been associated with an increased risk of respiratory disease, but assessments of specific respiratory infections in adults are lacking., Objectives: To estimate the rate of respiratory infection healthcare encounters in adults associated with acute increases in PM 2.5 concentrations., Methods: Using case-crossover methods, we studied 498,118 adult New York State residents with a primary diagnosis of influenza, bacterial pneumonia, or culture-negative pneumonia upon hospitalization or emergency department (ED) visit (2005-2016). We estimated the relative rate of healthcare encounters associated with increases in PM 2.5 in the previous 1-7 days and explored differences before (2005-2007), during (2008-2013), and after (2014-2016) implementation of air quality policies and economic changes., Results: Interquartile range increases in PM 2.5 over the previous 7 days were associated with increased excess rates (ERs) of culture-negative pneumonia hospitalizations (2.5%; 95% confidence interval [CI], 1.7-3.2%) and ED visits (2.5%; 95% CI, 1.4-3.6%), and increased ERs of influenza ED visits (3.9%; 95% CI, 2.1-5.6%). Bacterial pneumonia hospitalizations, but not ED visits, were associated with increases in PM 2.5 and, though imprecise, were of a similar magnitude to culture-negative pneumonia (Lag Day 6 ER, 2.3%; 95% CI, 0.3-4.3). Increased relative rates of influenza ED visits and culture-negative pneumonia hospitalizations were generally larger in the "after" period (P < 0.025 for both outcomes), compared with the "during" period, despite reductions in overall PM 2.5 concentrations., Conclusions: Increased rates of culture-negative pneumonia and influenza were associated with increased PM 2.5 concentrations during the previous week, which persisted despite reductions in PM 2.5 from air quality policies and economic changes. Though unexplained, this temporal variation may reflect altered toxicity of different PM 2.5 mixtures or increased pathogen virulence.

BACKGROUND In occupational epidemiology it is typically assumed that the relation between exposure, possibly transformed, and the risk of an adverse health outcome is linear in the parameters. Alternatively, exposure is transformed into a categorical variable. METHODS We used nonparametric regression to examine the linearity assumption for prostate and brain cancer mortality in a cohort of 46,400 autoworkers exposed to metalworking fluids. Using a nested case-control sample, we fit Cox proportional hazards models with penalized splines, in which we allowed the risk to be a smooth function of exposure to each of three types of metalworking fluids. Two dose metrics in addition to cumulative exposure were considered. RESULTS The shape of the dose-response curve for soluble metalworking fluids and each cancer was approximately piecewise linear, with a small increase in risk at lower exposures followed by a larger increase at exposures above a critical point. CONCLUSIONS This example illustrates that the penalized spline methodology can be easily applied to cohort studies to estimate smooth exposure-response curves.