Maternal factors and disparities associated with oral clefts.

INTRODUCTION: The epidemiology of oral clefts continually unfolds. Researchers have not reached consensus concerning the significance of maternal smoking, weight gain, diabetes, age, and education and the risk of oral clefts. The purpose of this study was to examine these factors associated with oral clefts in the US population. METHODS: The 2005 U.S. Natality Data File was utilized for this study. Bivariate analyses compared the characteristics of mothers of infants with and without oral clefts. Multivarlate analysis calculated adjusted odds ratios for various maternal characteristics overall and for each race/ethnic group. RESULTS: Significant bivariate associations with oral clefts were found for maternal age, race/ethnicity, education, tobacco use, and pregnancy-associated hypertension. Multivariate models found maternal age (OR = 0.98), race/ethnicity (OR = 0.36) for non-Hispanic Blacks (OR = 0.79 for Hispanics), and tobacco use (OR = 1.66) significant after adjustment for covariates. Across all race/ethnic groups maternal age (OR = 0.98) and smoking (OR = 1.66) were significantly associated with increased risk for oral cleft (OC). Non-Hispanic Blacks and Hispanics were at lower risk for OC regardless of the presence or absence of pregnancy-associated hypertension. CONCLUSIONS: Consistent with previous studies, maternal smoking was found to be associated with an increased risk of oral clefts. This association was significant for non-Hispanic Whites but not for non-Hispanic Blacks and Hispanics. A small inverse association was observed between maternal age, pregnancy-associated hypertension and the risk of oral clefts. This study confirms relationships found in previous studies but cannot establish causality. Further investigations of the risk factors for oral clefts would benefit from the study of gene-environment interactions.

Modulation of eotaxin-3 (CCL26) in alveolar type II epithelial cells.

Airway epithelial inflammation associated with emphysema, chronic bronchitis, chronic obstructive pulmonary disease (COPD) and asthma is regulated in part by alveolar type II cell chemokine signaling. Data suggest that resident lung cells use CCR3, CCR5 and CCR2 chemokine receptor/ligand systems to regulate the profile of leukocytes recruited in disease-associated inflammatory conditions. Thus studies were designed to test whether alveolar type II cells possess a Th1-activated CCR5-ligand system that modulates the Th2-activated CCR3/eotaxin-2 (CCL24), eotaxin-3 (CCL26) chemokine systems. The A549 alveolar type II epithelial-like cell culture model was used to demonstrate that alveolar type II cells constitutively express CCR5 which may be upregulated by MIP-1alpha (CCL3) whose expression was induced by the Th1 cytokines IL-1beta and IFN-gamma. Selective down-regulation of CCL26, but not CCL24, was observed in CCL3 and IL-4/CCL3 stimulated cells. Down-regulation was reversed by anti-CCR5 neutralizing antibody treatment. Thus, one mechanism through which Th1-activated CCCR5/ligand pathways modulate Th2-activated CCR3/ligand pathways is the differential down-regulation of CCL26 expression. Results suggest that the CCR3 and CCR5 receptor/ligand signaling pathways may be important targets for development of novel mechanism-based adjunctive therapies designed to abrogate the chronic inflammation associated with airway diseases.