Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts

Research output: Contribution to journalJournal articleResearchpeer-review

Diana B. P. Clemente, Maribel Casas, Nadia Vilahur, Haizea Begiristain, Mariona Bustamante, Anne-Elie Carsin, Mariana F. Fernández, Frans Fierens, Wilfried Gyselaers, Carmen Iñiguez, Bram G. Janssen, Wouter Lefebvre, Sabrina Llop, Nicolás Olea, Marie Pedersen, Nicky Pieters, Loreto Santa Marina, Anna Souto, Adonina Tardón, Charlotte Vanpoucke & 3 others Martine Vrijheid, Jordi Sunyer, Tim S Nawrot

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 association between prenatal 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 dataset were calculated using multiple linear regression and mixed models. We also performed a mediation analysis.

RESULTS: Pooled estimates indicated that a 10µg/m(3) increment in average NO2 exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% confidence interval (CI): -9.3, -0.3%). and a 48g decrease (95% CI: -87, -9g) in birth weight. However, the association with birth weight was significant for INMA (-66g; 95% CI: -111, -23g) but not for ENVIRONAGE (-20g; 95% CI: -101, 62g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, IQR increase: 140g; 95% CI: 43, 237g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0g) 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.

Original languageEnglish
JournalEnvironmental Health Perspectives
Volume124
Issue number5
Pages (from-to)659-665
Number of pages7
ISSN0091-6765
DOIs
Publication statusPublished - May 2016
Externally publishedYes

ID: 143934198