A Time Series Analysis of Air Pollution and Preterm Birth in Pennsylvania, 1997–2001

Preterm delivery can lead to serious infant health outcomes, including death and lifelong disability. Small increases in preterm delivery risk in relation to spatial gradients of air pollution have been reported, but previous studies may have controlled inadequately for individual factors. Using a time-series analysis, which eliminates potential confounding by individual risk factors that do not change over short periods of time, we investigated the effect of ambient outdoor particulate matter with diameter ≤10 μm (PM(10)) and sulfur dioxide on risk for preterm delivery. Daily counts of preterm births were obtained from birth records in four Pennsylvania counties from 1997 through 2001. We observed increased risk for preterm delivery with exposure to average PM(10) and SO(2) in the 6 weeks before birth [respectively, relative risk (RR) = 1.07; 95% confidence interval (CI), 0.98–1.18 per 50 μg/m(3) increase; RR = 1.15; 95% CI, 1.00–1. 32 per 15 ppb increase], adjusting for long-term preterm delivery trends, co-pollutants, and offsetting by the number of gestations at risk. We also examined lags up to 7 days before the birth and found an acute effect of exposure to PM(10) 2 days and 5 days before birth (respectively, RR = 1.10; 95% CI, 1.00–1.21; RR = 1.07; 95% CI, 0.98–1.18) and SO(2) 3 days before birth (RR = 1.07; 95% CI, 0.99–1.15), adjusting for covariates, including temperature, dew point temperature, and day of the week. The results from this time-series analysis, which provides evidence of an increase in preterm birth risk with exposure to PM(10) and SO(2), are consistent with prior investigations of spatial contrasts

Cellular immune responses in amniotic fluid of women with preterm labor and intraâ amniotic infection or intraâ amniotic inflammation

ProblemPreterm birth is commonly preceded by preterm labor, a syndrome that is causally linked to both intraâ amniotic infection and intraâ amniotic inflammation. However, the stereotypical cellular immune responses in these two clinical conditions are poorly understood.Method of studyAmniotic fluid samples (n = 26) were collected from women diagnosed with preterm labor and intraâ amniotic infection (amniotic fluid ILâ 6 concentrations â ¥2.6 ng/mL and culturable microorganisms, n = 10) or intraâ amniotic inflammation (amniotic fluid ILâ 6 concentrations â ¥2.6 ng/mL without culturable microorganisms, n = 16). Flow cytometry was performed to evaluate the phenotype and number of amniotic fluid leukocytes. Amniotic fluid concentrations of classical proâ inflammatory cytokines, type 1 and type 2 cytokines, and Tâ cell chemokines were determined using immunoassays.ResultsWomen with spontaneous preterm labor and intraâ amniotic infection had (a) a greater number of total leukocytes, including neutrophils and monocytes/macrophages, in amniotic fluid; (b) a higher number of total T cells and CD4+ T cells, but not CD8+ T cells or B cells, in amniotic fluid; and (c) increased amniotic fluid concentrations of ILâ 6, ILâ 1β, and ILâ 10, compared to those with intraâ amniotic inflammation. However, no differences in amniotic fluid concentrations of Tâ cell cytokines and chemokines were observed between these two clinical conditions.ConclusionThe cellular immune responses observed in women with preterm labor and intraâ amniotic infection are more severe than in those with intraâ amniotic inflammation, and neutrophils, monocytes/macrophages, and CD4+ T cells are the main immune cells responding to microorganisms that invade the amniotic cavity. These findings provide insights into the intraâ amniotic immune mechanisms underlying the human syndrome of preterm labor.The relative distribution of innate and adaptive immune cell subsets in amniotic fluid of women with preterm labor and intraâ amniotic inflammation. Flow cytometry analysis is shown as a tâ SNE plot.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151891/1/aji13171_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151891/2/aji13171.pd

Widespread Epigenetic Abnormalities Suggest a Broad DNA Methylation Erasure Defect in Abnormal Human Sperm

Male-factor infertility is a common condition, and etiology is unknown for a high proportion of cases. Abnormal epigenetic programming of the germline is proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. During germ cell maturation and gametogenesis, cells of the germ line undergo extensive epigenetic reprogramming. This process involves widespread erasure of somatic-like patterns of DNA methylation followed by establishment of sex-specific patterns by de novo DNA methylation. Incomplete reprogramming of the male germ line could, in theory, result in both altered sperm DNA methylation and compromised spermatogenesis.We determined concentration, motility and morphology of sperm in semen samples collected by male members of couples attending an infertility clinic. Using MethyLight and Illumina assays we measured methylation of DNA isolated from purified sperm from the same samples. Methylation at numerous sequences was elevated in DNA from poor quality sperm.This is the first report of a broad epigenetic defect associated with abnormal semen parameters. Our results suggest that the underlying mechanism for these epigenetic changes may be improper erasure of DNA methylation during epigenetic reprogramming of the male germ line