Objective Our aim was to assess critical windows of weekly exposure to ambient NO2 on ultrasound-measured fetal growth in a cohort of pregnant women from Valencia, Spain, (INMA project). Methods Ultrasounds were performed around 12, 20 and 34 weeks of pregnancy for all women (n=787) and measurements of biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL) were used to estimate fetal weight (EFW). A longitudinal growth curve for each parameter was fit with linear mixed models, adjusted for maternal height, weight, age, parity, and ethnicity. Growth curves were used to calculate SD-scores at week 34, which served as outcomes in this analysis. Weekly residential NO2 exposure was estimated by temporally adjusted Land-Use Regression based on ambient NO2 concentrations for 93 sampling points covering the study area and the existing ambient monitoring network of the city. Distributed lag non linear models, adjusted for socioeconomic and lifestyle variables, were used to explore critical weeks of exposure. Effect estimates were summarized as percent change (%CH) per 10 μg/m3 increase in NO2. Results NO2 exposure in gestational weeks 4-8 was inversely associated with BPD, with peak magnitude at week 5 (%CH=-0.87, 95%CI=-1.49, -0.25). NO2 exposure was inversely associated with AC in weeks 16-21 and with EFW in weeks 18-21. In both cases the association peaked at week 19 [AC %CH=-0.87 (-1.37, -0.25) and EFW %CH=-0.65 (-1.20, -0.09)]. NO2 exposure was not associated with FL. Discussion This study indicates that early pregnancy may be a critical window of exposure to outdoor NO2 for head size and mid pregnancy may be for weight. Results were in line with a previous study using the same data, but the present method allowed for an agnostic and refined assessment of potential windows of susceptibility without using a priori definitions (e.g.trimesters). Funding: ISCIII-FEDER ( PI13/1944, MS11/0178, MSII16/00051, MS16/00128) and Alicia Koplowitz Foundation 2017.
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