Association of Prenatal and Perinatal Exposures to Particulate Matter With Changes in Hemoglobin A<sub>1c</sub> Levels in Children Aged 4 to 6 Years
Authors: Emily C. Moody, Alejandra Cantoral, Marcela Tamayo-Ortiz, Ma. Luisa Pizano-Zárate, Lourdes Schnaas, Itai Kloog, Emily Oken, Brent Coull, Andrea Baccarelli, Martha M. Téllez-Rojo, Robert O. Wright, Allan C. Just
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Environmental risk factors for childhood type 2 diabetes, an increasing global problem, are understudied. Air pollution exposure has been reported to be a risk factor for this condition. <h3>Objective</h3> To examine the association between prenatal and perinatal exposures to fine particulate matter with a diameter less than 2.5 μm (PM<sub>2.5</sub>) and changes in hemoglobin A<sub>1c</sub>(HbA<sub>1c</sub>), a measure of glycated hemoglobin and marker of glucose dysregulation, in children aged 4 to 7 years. <h3>Design, Setting, and Participants</h3> The Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) study, a birth cohort study conducted in Mexico City, Mexico, recruited pregnant women from July 3, 2007, to February 21, 2011, through public health maternity clinics. The present analysis includes 365 mother-child pairs followed up until the child was approximately 7 years of age. This study included data from only study visits at approximately 4 to 5 years (visit 1) and 6 to 7 years (visit 2) post partum because HbA<sub>1c</sub>levels were not measured in earlier visits. The data were analyzed from March 11, 2018, to May 3, 2019. <h3>Exposures</h3> Daily PM<sub>2.5</sub>exposure estimates at participants' home addresses from 4 weeks prior to mothers' date of last menstrual period (LMP), a marker of the beginning of pregnancy, to 12 weeks after the due date. Exposure was estimated from satellite measurements and calibrated against ground PM<sub>2.5</sub>measurements, land use, and meteorological variables. <h3>Main Outcomes and Measures</h3> Outcomes included HbA<sub>1c</sub>levels at 4 to 5 years and 6 to 7 years of age, and the change in the level from the former age group to the latter. <h3>Results</h3> The sample included 365 children, of whom 184 (50.4%) were girls. The mean (range) age of the children was 4.8 (4.0-6.4) years at visit 1, and 6.7 (6.0-9.7) years at visit 2. At the time of delivery, the mean (range) age of the mothers was 27.7 (18.3-44.4) years, with a mean (range) prepregnancy body mass index of 26.4 (18.5-43.5). The mean (SD) prenatal PM<sub>2.5</sub>exposure (22.4 μg/m<sup>3</sup>[2.7 μg/m<sup>3</sup>]) was associated with an annual increase in HbA<sub>1c</sub>levels of 0.25% (95% CI, 0.004%-0.50%) from age 4 to 5 years to 6 to 7 years compared with exposure at 12 μg/m<sup>3</sup>, the national regulatory standard in Mexico. Sex-specific effect estimates were statistically significant for girls (β = 0.21%; 95% CI, 0.10% to 0.32%) but not for boys (β = 0.31%; 95% CI, −0.09% to 0.72%). The statistically significant windows of exposure were from week 28 to 50.6 after the mother's LMP for the overall cohort and from week 11 to the end of the study period for girls. Lower HbA<sub>1c</sub>levels were observed at age 4 to 5 years in girls (β = −0.72%; 95% CI, −1.31% to −0.13%, exposure window from week 16 to 37.3) and boys (β = −0.98%; 95% CI, −1.70% to −0.26%, exposure window from the beginning of the study period to week 32.7), but no significant association was found in the overall cohort (β = −0.13%; 95% CI, −1.27% to 1.01%). There was no significant association between PM<sub>2.5</sub>exposure and HbA<sub>1c</sub>level at age 6 to 7 years in any group. <h3>Conclusions and Relevance</h3> The findings of this study suggest that prenatal and perinatal exposures to PM<sub>2.5</sub>are associated with changes in HbA<sub>1c</sub>, which are indicative of glucose dysregulation, in early childhood. Further research is needed because this finding may represent a risk factor for childhood or adolescent diabetes.