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

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; Martine Vrijheid; Jordi Sunyer; Tim S Nawrot

doi:10.1289/ehp.1408981

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

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 VanpouckeMartine Vrijheid, Jordi Sunyer, Tim S Nawrot

Research output: Contribution to journal › Journal article › Research › peer-review

112 Citations (Scopus)

Abstract

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 language	English
Journal	Environmental Health Perspectives
Volume	124
Issue number	5
Pages (from-to)	659-665
Number of pages	7
ISSN	0091-6765
DOIs	https://doi.org/10.1289/ehp.1408981
Publication status	Published - May 2016
Externally published	Yes

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Clemente, D. B. P., Casas, M., Vilahur, N., Begiristain, H., Bustamante, M., Carsin, A-E., Fernández, M. F., Fierens, F., Gyselaers, W., Iñiguez, C., Janssen, B. G., Lefebvre, W., Llop, S., Olea, N., Pedersen, M., Pieters, N., Santa Marina, L., Souto, A., Tardón, A., ... Nawrot, T. S. (2016). Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts. Environmental Health Perspectives, 124(5), 659-665. https://doi.org/10.1289/ehp.1408981

Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts. / Clemente, Diana B. P.; Casas, Maribel; Vilahur, Nadia; Begiristain, Haizea; Bustamante, Mariona; Carsin, Anne-Elie; Fernández, Mariana F.; Fierens, Frans; Gyselaers, Wilfried; Iñiguez, Carmen; Janssen, Bram G.; Lefebvre, Wouter; Llop, Sabrina; Olea, Nicolás; Pedersen, Marie; Pieters, Nicky; Santa Marina, Loreto; Souto, Anna; Tardón, Adonina; Vanpoucke, Charlotte; Vrijheid, Martine; Sunyer, Jordi; Nawrot, Tim S.

In: Environmental Health Perspectives, Vol. 124, No. 5, 05.2016, p. 659-665.

Research output: Contribution to journal › Journal article › Research › peer-review

Clemente, DBP, Casas, M, Vilahur, N, Begiristain, H, Bustamante, M, Carsin, A-E, 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', Environmental Health Perspectives, vol. 124, no. 5, pp. 659-665. https://doi.org/10.1289/ehp.1408981

Clemente, Diana B. P. ; Casas, Maribel ; Vilahur, Nadia ; Begiristain, Haizea ; Bustamante, Mariona ; Carsin, Anne-Elie ; Fernández, Mariana F. ; Fierens, Frans ; Gyselaers, Wilfried ; Iñiguez, Carmen ; Janssen, Bram G. ; Lefebvre, Wouter ; Llop, Sabrina ; Olea, Nicolás ; Pedersen, Marie ; Pieters, Nicky ; Santa Marina, Loreto ; Souto, Anna ; Tardón, Adonina ; Vanpoucke, Charlotte ; Vrijheid, Martine ; Sunyer, Jordi ; Nawrot, Tim S. / Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts. In: Environmental Health Perspectives. 2016 ; Vol. 124, No. 5. pp. 659-665.

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

abstract = "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.",

author = "Clemente, {Diana B. P.} and Maribel Casas and Nadia Vilahur and Haizea Begiristain and Mariona Bustamante and Anne-Elie Carsin and Fern{\'a}ndez, {Mariana F.} and Frans Fierens and Wilfried Gyselaers and Carmen I{\~n}iguez and Janssen, {Bram G.} and Wouter Lefebvre and Sabrina Llop and Nicol{\'a}s Olea and Marie Pedersen and Nicky Pieters and {Santa Marina}, Loreto and Anna Souto and Adonina Tard{\'o}n and Charlotte Vanpoucke and Martine Vrijheid and Jordi Sunyer and Nawrot, {Tim S}",

year = "2016",

month = may,

doi = "10.1289/ehp.1408981",

language = "English",

volume = "124",

pages = "659--665",

journal = "Environmental Health Perspectives",

issn = "0091-6765",

publisher = "National Institute of Environmental Health Sciences",

number = "5",

}

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 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.

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 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.

U2 - 10.1289/ehp.1408981

DO - 10.1289/ehp.1408981

M3 - Journal article

C2 - 26317635

VL - 124

SP - 659

EP - 665

JO - Environmental Health Perspectives

JF - Environmental Health Perspectives

SN - 0091-6765

IS - 5

ER -