title: Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts.
abstract: 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.
  
  
  
  We investigated whether placental mtDNA content is a possible mediator of the association between prenatal nitrogen dioxide (NO2) exposure and birth weight.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight.
  
  
  
  Clemente DB, Casas M, Vilahur N, Begiristain H, Bustamante M, Carsin AE, Fernández MF, Fierens F, Gyselaers W, Iñiguez C, Janssen BG, Lefebvre W, Llop S, Olea N, Pedersen M, Pieters N, Santa Marina L, Souto A, Tardón A, Vanpoucke C, Vrijheid M, Sunyer J, Nawrot TS. 2016. Prenatal ambient air pollution, placental mitochondrial DNA content, and birth weight in the INMA (Spain) and ENVIRONAGE (Belgium) birth cohorts. Environ Health Perspect 124:659-665; http://dx.doi.org/10.1289/ehp.1408981.
authors: Center for Environmental Sciences, Hasselt University, Diepenbeek, Belgium.
authors: Diana B P
authors: DB
authors: Clemente
authors: Maribel
authors: M
authors: Casas
authors: Nadia
authors: N
authors: Vilahur
authors: Haizea
authors: H
authors: Begiristain
authors: Mariona
authors: M
authors: Bustamante
authors: Anne-Elie
authors: AE
authors: Carsin
authors: Mariana F
authors: MF
authors: Fernández
authors: Frans
authors: F
authors: Fierens
authors: Wilfried
authors: W
authors: Gyselaers
authors: Carmen
authors: C
authors: Iñiguez
authors: Bram G
authors: BG
authors: Janssen
authors: Wouter
authors: W
authors: Lefebvre
authors: Sabrina
authors: S
authors: Llop
authors: Nicolás
authors: N
authors: Olea
authors: Marie
authors: M
authors: Pedersen
authors: Nicky
authors: N
authors: Pieters
authors: Loreto
authors: L
authors: Santa Marina
authors: Ana
authors: A
authors: Souto
authors: Adonina
authors: A
authors: Tardón
authors: Charlotte
authors: C
authors: Vanpoucke
authors: Martine
authors: M
authors: Vrijheid
authors: Jordi
authors: J
authors: Sunyer
authors: Tim S
authors: TS
authors: Nawrot
mesh_terms: D000393:Air Pollutants; D000397:Air Pollution / Q000706:statistics & numerical data*; D001724:Birth Weight / Q000502:physiology*; D004272:DNA, Mitochondrial; D005260:Female; D047109:Fetal Development; D006801:Humans; D018811:Maternal Exposure / Q000706:statistics & numerical data*; D010920:Placenta / Q000502:physiology*; D011247:Pregnancy; D013030:Spain
chemical_list: D000393:Air Pollutants; D004272:DNA, Mitochondrial