Role of antenatal anxiety in the relationship between maternal exposure to nitrogen dioxide and small for gestational age: A birth cohort study.

ABSTRACT

BACKGROUND: Both Nitrogen dioxide (NO2) exposure and antenatal anxiety have individually been associated with small for gestational age (SGA). Little is known, however, about whether there is effect modification of antenatal anxiety on NO2-related SGA. METHODS: The prospective birth cohort study included 1823 mother-newborn pairs in Guangzhou, China, from January 2017 to April 2020. Exposure to NO2 during the pre-conceptional and prenatal periods was estimated using an inverse distance weighted method. Antenatal anxiety was assessed by Trait Anxiety Inventory. SGA was determined by the Chinese gestational age- and sex-specific birthweight standards. Cox proportional hazards regression models was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for SGA as per 10 µg/m3 increase in NO2. Modifying effects of trait anxiety on NO2-related SGA were identified by stratified analyses, and three-dimensional response surface plots and two-dimensional heat maps. RESULTS: Each 10 µg/m3 increase in NO2 exposure during the third trimester was significantly associated with SGA risk among overall participants (HR = 1.221, 95 % CI 1.014-1.471) and primipara (HR = 1.271, 95 % CI 1.023-1.579). We found significant effect modification of anxiety level for NO2-related SGA in the third trimester (Pinteraction < 0.05). Pregnant women with higher levels of trait anxiety were more likely to deliver SGA newborns, particularly for those with high trait anxiety (HR = 1.781, 95 % CI 1.007-2.945). Primiparous women were more susceptible. CONCLUSIONS: This study provides evidence that antenatal trait anxiety may modify the effects of maternal NO2 exposure on SGA risk. The third trimester could be a critical window of susceptibility.