TY - JOUR
T1 - Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts
AU - Clemente, Diana B. P.
AU - Casas, Maribel
AU - Vilahur, Nadia
AU - Begiristain, Haizea
AU - Bustamante, Mariona
AU - Carsin, Anne-Elie
AU - Fernández, Mariana F.
AU - Fierens, Frans
AU - Gyselaers, Wilfried
AU - Iñiguez, Carmen
AU - Janssen, Bram G.
AU - Lefebvre, Wouter
AU - Llop, Sabrina
AU - Olea, Nicolás
AU - Pedersen, Marie
AU - Pieters, Nicky
AU - Santa Marina, Loreto
AU - Souto, Anna
AU - Tardón, Adonina
AU - Vanpoucke, Charlotte
AU - Vrijheid, Martine
AU - Sunyer, Jordi
AU - Nawrot, Tim S
PY - 2016/5
Y1 - 2016/5
N2 - Background: Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in mechanisms linking air pollution and fetal growth restriction. oBjective: We investigated whether placental mtDNA content is a possible mediator of the asso-ciation between prenatal nitrogen dioxide (NO2) exposure and birth weight. Methods: We used data from two independent European cohorts: INMA (n = 376; Spain) and ENVIRONAGE (n = 550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled data set were calculated using multiple linear regression and mixed models. We also performed a mediation analysis. results: Pooled estimates indicated that a 10-μg/m3 increment in average NO2 exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% CI: –9.3, –0.3%) and a 48-g decrease (95% CI: –87, –9 g) in birth weight. However, the association with birth weight was significant for INMA (–66 g; 95% CI: –111, –23 g) but not for ENVIRONAGE (–20 g; 95% CI: –101, 62 g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, interquartile range increase: 140 g; 95% CI: 43, 237 g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0 g) of the association between prenatal NO2 and birth weight was mediated by changes in placental mtDNA content. conclusion: Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight.
AB - Background: Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in mechanisms linking air pollution and fetal growth restriction. oBjective: We investigated whether placental mtDNA content is a possible mediator of the asso-ciation between prenatal nitrogen dioxide (NO2) exposure and birth weight. Methods: We used data from two independent European cohorts: INMA (n = 376; Spain) and ENVIRONAGE (n = 550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled data set were calculated using multiple linear regression and mixed models. We also performed a mediation analysis. results: Pooled estimates indicated that a 10-μg/m3 increment in average NO2 exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% CI: –9.3, –0.3%) and a 48-g decrease (95% CI: –87, –9 g) in birth weight. However, the association with birth weight was significant for INMA (–66 g; 95% CI: –111, –23 g) but not for ENVIRONAGE (–20 g; 95% CI: –101, 62 g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, interquartile range increase: 140 g; 95% CI: 43, 237 g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0 g) of the association between prenatal NO2 and birth weight was mediated by changes in placental mtDNA content. conclusion: Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight.
U2 - 10.1289/ehp.1408981
DO - 10.1289/ehp.1408981
M3 - Journal article
C2 - 26317635
SN - 0091-6765
VL - 124
SP - 659
EP - 665
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
IS - 5
ER -