Air Pollution Exposure and Markers of Placental Growth and Function: The Generation R Study

Edith H. van den Hooven,^1,2,3 Frank H. Pierik,² Yvonne de Kluizenaar,² Albert Hofman,³ Sjoerd W. van Ratingen,² Peter Y.J. Zandveld,² Henk Russcher,⁴ Jan Lindemans,⁴ Henk M.E. Miedema,² Eric A.P. Steegers,⁵ and Vincent W.V. Jaddoe^1,3,6

¹The Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands; ²Urban Environment and Safety, TNO (Netherlands Organization for Applied Scientific Research), Utrecht, the Netherlands; ³Department of Epidemiology, ⁴Department of Clinical Chemistry, ⁵Department of Obstetrics and Gynaecology, and ⁶Department of Paediatrics, Erasmus Medical Center, Rotterdam, the Netherlands

Abstract

Background: Air pollution exposure during pregnancy might affect placental growth and function, perhaps leading to pregnancy complications.

Objective: We prospectively evaluated the associations of maternal air pollution exposure with markers of placental growth and function among 7,801 pregnant women in the Netherlands.

Methods: We estimated levels of particulate matter ≤ 10 µm in aerodynamic diameter (PM₁₀) and nitrogen dioxide (NO₂) at the home address for different periods during pregnancy using dispersion modeling techniques. Pro- and anti-angiogenic factors [placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1), respectively] were measured in first- and second-trimester maternal blood and in fetal cord blood samples at delivery. Pulsatility index of the uterine and umbilical arteries was measured by Doppler ultrasound in second and third trimester, and notching was assessed in third trimester. Placenta weight and birth weight were obtained from medical records.

Results: Higher PM₁₀ and NO₂ exposure levels were associated with lower second-trimester maternal sFlt-1 and PlGF levels. PM₁₀ and NO₂ exposures averaged over total pregnancy were associated with higher sFlt-1 and lower PlGF levels in fetal cord blood, consistent with an anti-angiogenic state. PM₁₀ and NO₂ exposures were not consistently associated with second- or third-trimester placental resistance indices. NO₂ exposure was associated with third-trimester notching (odds ratio 1.33; 95% CI: 0.99, 1.78 per 10-μg/m³ increase in the prior 2 months). PM₁₀ and NO₂ exposures were associated with lower placenta weight (–11.8 g; 95% CI: –20.9, –2.7, and –10.7 g; 95% CI: –19.0, –2.4, respectively, per 10‑μg/m³ increase in the prior 2 months), but not with placenta to birth weight ratio.

Conclusions: Our results suggest that maternal air pollution exposure may influence markers of placental growth and function. Future studies are needed to confirm these findings and explore the maternal and fetal consequences.

Key words: air pollution, dispersion modeling, nitrogen dioxide, particulate matter, placenta, pregnancy. 

Environ Health Perspect 120:1753–1759 (2012). http://dx.doi.org/10.1289/ehp.1204918 [Online 24 August 2012]

Address correspondence to E.H. van den Hooven, The Generation R Study Group, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands. Telephone: 31 (0) 10 7043405, Fax: 31 (0) 10 7044645. E-mail: e.vandenhooven@erasmusmc.nl

Supplemental Material is available online (http://dx.doi.org/10.1289/ehp.1204918).

The Generation R Study is conducted by the Erasmus Medical Center Rotterdam in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, the Rotterdam Homecare Foundation, and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR-MDC), Rotterdam. We gratefully acknowledge the contribution of participating mothers and children, general practitioners, hospitals, midwives, and pharmacies in Rotterdam. We also thank E. Meijer, H. Vos, and R. Sterkenburg from TNO (Netherlands Organization for Applied Scientific Research) Urban Environment and Safety for exposure assessment and data linkage and providing air pollution maps, and the DCMR Environmental Protection Agency Rijnmond (DCMR) for kindly supplying data.

The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organisation for Scientific Research (NWO), the Ministry of Health, Welfare and Sport, and the Ministry of Youth and Families. V.W.V.J. reports receipt of funding from the Netherlands Organization for Health Research and Development (ZonMw 90700303, 916.10159). TNO received funding from The Netherlands Ministry of Infrastructure and the Environment to support exposure assessment.

The authors declare they have no actual or potential competing financial interests.

Received 3 January 2012; Accepted 24 August 2012; Online 24 August 2012.