title: Air pollution exposure and markers of placental growth and function: the generation R study.
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.
authors.affiliation: The Generation R Study Group, Erasmus Medical Center, Rotterdam, the Netherlands. e.vandenhooven@erasmusmc.nl
authors.forename: Edith H
authors.initials: EH
authors.lastname: van den Hooven
authors.forename: Frank H
authors.initials: FH
authors.lastname: Pierik
authors.forename: Yvonne
authors.initials: Y
authors.lastname: de Kluizenaar
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Sjoerd W
authors.initials: SW
authors.lastname: van Ratingen
authors.forename: Peter Y J
authors.initials: PY
authors.lastname: Zandveld
authors.forename: Henk
authors.initials: H
authors.lastname: Russcher
authors.forename: Jan
authors.initials: J
authors.lastname: Lindemans
authors.forename: Henk M E
authors.initials: HM
authors.lastname: Miedema
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D001724:Birth Weight / Q000187:drug effects*; D002947:Cities; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D047109:Fetal Development / Q000187:drug effects*; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D018811:Maternal Exposure; D009426:Netherlands; D009585:Nitrogen Dioxide / Q000633:toxicity*; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D000072483:Placenta Growth Factor; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000097:blood; D011446:Prospective Studies; D012307:Risk Factors; D018608:Ultrasonography, Doppler; D016216:Ultrasonography, Prenatal; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000393:Air Pollutants; C000608036:PGF protein, human; D052638:Particulate Matter; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D009585:Nitrogen Dioxide