Identifying the critical windows and joint effects of temperature and PM2.5 exposure on small for gestational age

The potential critical windows for extreme ambient temperature, air pollution exposure and small for gestational age (SGA) are still unclear, and no study has explored their joint effects on SGA. In a national multi-center prospective cohort, we included 179,761 pairs of mother-infant from 16 counties of 8 provinces in China during 2014-2018. Daily averaged temperature and PM_2.5 concentration were matched to the maternal residential address to estimate personal exposure. Extreme temperature exposures were categorized by a series of percentile in each meteorological and geographic division for the entire pregnancy, each trimester and gestational week (GA-week). Generalized linear mixed models (GLMMs) and distributed lag nonlinear models (DLNMs) were used to estimate the whole pregnancy-, trimester-specific, and weekly-specific associations of extreme temperature and PM_2.5 exposures with SGA. Combined effects were evaluated with the relative excess risk due to interaction (RERI) and proportion attributable to interaction (AP). We observed that by referring to temperature at the 41st - 50th percentile, heat (>90th percentile) exposure during 13th - 29th GA-weeks was associated with SGA; odds ratio (OR) and 95 % confidence intervals (CI) was 1.16 (1.06, 1.28). For cold (<=10th percentile), inverse associations were observed during the 1st - 8th GA-weeks. PM_2.5 exposure during the 2nd - 5th and 19th - 27th GA-weeks was associated with SGA, with the strongest association in the 2nd GA-week (OR = 1.0017, 95 %CI: 1.0001, 1.0034, for a 10 μg/m³ increase). No interactive effects between ambient temperature and PM_2.5 on SGA were observed. Our findings suggest the weekly susceptibility windows for heat and PM_2.5 exposure were primarily the gestational weeks within the 2nd trimester, therefore, corresponding protective measures should be conveyed to pregnant women during routine prenatal visits to reduce exposures.