Skip to main content

Advertisement

SpringerLink
Log in

Individual exposure to urban air pollution and its correlation with placental angiogenic markers in the first trimester of pregnancy, in São Paulo, Brazil

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Pollution of the atmosphere is known that may lead to adverse obstetric outcomes, including fetal growth restriction, gestational hypertension, and preeclampsia. Such disorders are correlated with imbalances in angiogenic factors, which may also be involved in the pathological mechanism as the pollutants impact placental and maternal physiology. In the first trimester of gestation, this study assessed the outcomes of personal maternal short period exposure to air pollution on soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PLGF) of pregnant women blood concentrations. This was a cross-sectional study, held in the city of São Paulo, Brazil, and conducted with low-risk pregnant women, who carried personal passive nitrogen dioxide (NO2) and ozone (O3) monitors for about a few days preceding the ultrasound evaluation, and on this day, the venous blood sample was collected to measure the angiogenic factors sFlt1 and PLGF and their ratio (sFlt1/PLGF) by enzyme-linked immunosorbent assay (ELISA). By means of multiple regression models, the effect of the studied pollutants on the log-transformed concentrations of the angiogenic factors was evaluated. One hundred thirty-one patients were included. The log of the sFlt1/PLGF ratio increased with rising NO2 levels (p = 0.021 and beta = 0.206), and the log of the PLGF concentration showed a negative correlation with NO2 (p = 0.008 and beta = − 0.234). NO2, an indicator of the levels of primary air pollutants, presented significant positive correlation with an increased sFlt1/PLGF ratio and diminished PLGF levels, which may reflect an antiangiogenic state generated by air pollution exposure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

References

  • Andikyan VM, Voloshchuk IN, Kovganko PA, Clemente JM (2000) Morphofunctional changes in the placenta after ozone therapy. Bull Exp Biol Med 130(7):715–718

    Article  CAS  Google Scholar 

  • André CDSD, André PAD, Rocha FM, Saldiva PHN, Oliveira RCD, Singer JM (2014) Reliability of reflectance measures in passive filters. Atmos Environ 92:178–181

    Article  Google Scholar 

  • Araneda S, Commin L, Atlagich M, Kitahama K, Parraguez VH, Pequignot JM, Dalmaz Y (2008) VEGF overexpression in the astroglial cells of rat brainstem following ozone exposure. Neurotoxicology 29(6):920–927

    Article  CAS  Google Scholar 

  • Bergen NE, Bouwland-Both MI, Steegers-Theunissen RP, Hofman A, Russcher H, Lindemans J, Jaddoe VW, Steegers EA (2015) Early pregnancy maternal and fetal angiogenic factors and fetal and childhood growth: the Generation R Study. Hum Reprod 30(6):1302–1313

    Article  CAS  Google Scholar 

  • Blum JL, Chen LC, Zelikoff JT (2017) Exposure to ambient particulate matter during specific gestational periods produces adverse obstetric consequences in mice. Environ Health Perspect 125(7):077020

    Article  Google Scholar 

  • Brook RD, Rajagopalan S, Pope CA, Brook JR, Bhatnagar A, Diez-Roux AV, Holguin F, Hong Y, Luepker RV, Mittleman MA, Peters A, Siscovick D, Smith SC, Whitsel L, Kaufman JD, C. O. t. K. I. C. D. American Heart Association Council on Epidemiology and Prevention, and Council on Nutrition, P.ysical Activity and Metabolism (2010) Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 121(21):2331–2378

    Article  CAS  Google Scholar 

  • Canfield MA, Ramadhani TA, Langlois PH, Waller DK (2006) Residential mobility patterns and exposure misclassification in epidemiologic studies of birth defects. J Expo Sci Environ Epidemiol 16(6):538–543

    Article  Google Scholar 

  • Cao Z, Meng L, Zhao Y, Liu C, Yang Y, Su X, Fu Q, Wang D, Hua J (2019) Maternal exposure to ambient fine particulate matter and fetal growth in Shanghai, China. Environ Health 18(1):49

    Article  Google Scholar 

  • Carneiro MFH, Ribeiro FQ, Fernandes-Filho FN, Lobo DJA, Barbosa F Jr, Rhoden CR, Mauad T, Saldiva PHN, Carvalho-Oliveira R (2011) Pollen abortion rates, nitrogen dioxide by passive diffusive tubes and bioaccumulation in tree barks are effective in the characterization of air pollution. Environ Exp Bot 72:272–277

    Article  CAS  Google Scholar 

  • Conceição GM, Miraglia SG, Kishi HS, Saldiva PH, Singer JM (2001) Air pollution and child mortality: a time-series study in São Paulo, Brazil. Environ Health Perspect 109(Suppl 3):347–350

    Article  Google Scholar 

  • Costa RA, Hoshida MS, Alves EA, Zugaib M, Francisco RP (2016) Preeclampsia and superimposed preeclampsia: the same disease? The role of angiogenic biomarkers. Hypertens Pregnancy 35(2):139–149

    Article  CAS  Google Scholar 

  • Costa S, Ferreira J, Silveira C, Costa C, Lopes D, Relvas H, Borrego C, Roebeling P, Miranda AI, Teixeira JP (2014) Integrating health on air quality assessment--review report on health risks of two major European outdoor air pollutants: PM and NO2. J Toxicol Environ Health B Crit Rev 17(6):307–340

    Article  CAS  Google Scholar 

  • da Silva AS, Cardoso MR, Meliefste K, Brunekreef B (2006) Use of passive diffusion sampling method for defining NO2 concentrations gradient in São Paulo, Brazil. Environ Health 5:19

    Article  Google Scholar 

  • de Melo JO, Soto SF, Katayama IA, Wenceslau CF, Pires AG, Veras MM, Furukawa LN, de Castro I, Saldiva PH, Heimann JC (2015) Inhalation of fine particulate matter during pregnancy increased IL-4 cytokine levels in the fetal portion of the placenta. Toxicol Lett 232(2):475–480

    Article  Google Scholar 

  • de Oliveira BF, Chacra AP, Frauches TS, Vallochi A, Hacon S (2014) A curated review of recent literature of biomarkers used for assessing air pollution exposures and effects in humans. J Toxicol Environ Health B Crit Rev 17(7–8):369–410

    Article  Google Scholar 

  • Demir R, Seval Y, Huppertz B (2007) Vasculogenesis and angiogenesis in the early human placenta. Acta Histochem 109(4):257–265

    Article  CAS  Google Scholar 

  • Guimarães Filho HA, da Costa LL, Araújo Júnior E, Nardozza LM, Nowak PM, Moron AF, Mattar R, Pires CR (2008) Placenta: angiogenesis and vascular assessment through three-dimensional power Doppler ultrasonography. Arch Gynecol Obstet 277(3):195–200

    Article  Google Scholar 

  • Hahad O, Lelieveld J, Birklein F, Lieb K, Daiber A, Münzel T (2020) Ambient air pollution increases the risk of cerebrovascular and neuropsychiatric disorders through induction of inflammation and oxidative stress. Int J Mol Sci 21(12)

  • Hettfleisch K, Bernardes LS, Carvalho MA, Pastro LD, Vieira SE, Saldiva SR, Saldiva P, Francisco RP (2017) Short-term exposure to urban air pollution and influences on placental vascularization indexes. Environ Health Perspect 125(4):753–759

    Article  CAS  Google Scholar 

  • Janssen BG, Godderis L, Pieters N, Poels K, Kiciński M, Cuypers A, Fierens F, Penders J, Plusquin M, Gyselaers W, Nawrot TS (2013) Placental DNA hypomethylation in association with particulate air pollution in early life. Part Fibre Toxicol 10:22

    Article  CAS  Google Scholar 

  • Jilani MH, Simon-Friedt B, Yahya T, Khan AY, Hassan SZ, Kash B, Blankstein R, Blaha MJ, Virani SS, Rajagopalan S, Cainzos-Achirica M, Nasir K (2020) Associations between particulate matter air pollution, presence and progression of subclinical coronary and carotid atherosclerosis: a systematic review. Atherosclerosis 306:22–32

    Article  CAS  Google Scholar 

  • Kannan S, Misra DP, Dvonch JT, Krishnakumar A (2006) Exposures to airborne particulate matter and adverse perinatal outcomes: a biologically plausible mechanistic framework for exploring potential effect modification by nutrition. Environ Health Perspect 114(11):1636–1642

    Article  CAS  Google Scholar 

  • Kaufmann P, Black S, Huppertz B (2003) Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol Reprod 69(1):1–7

    Article  CAS  Google Scholar 

  • Kaufmann P, Mayhew TM, Charnock-Jones DS (2004) Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy. Placenta 25(2–3):114–126

    Article  CAS  Google Scholar 

  • Khalil A, Maiz N, Garcia-Mandujano R, Penco JM, Nicolaides KH (2016) Longitudinal changes in maternal serum placental growth factor and soluble fms-like tyrosine kinase-1 in women at increased risk of pre-eclampsia. Ultrasound Obstet Gynecol 47(3):324–331

    Article  CAS  Google Scholar 

  • Klepac P, Locatelli I, Korošec S, Künzli N, Kukec A (2018) Ambient air pollution and pregnancy outcomes: a comprehensive review and identification of environmental public health challenges. Environ Res 167:144–159

    Article  CAS  Google Scholar 

  • Lavigne E, Yasseen AS 3rd, Stieb DM, Hystad P, van Donkelaar A, Martin RV, Brook JR, Crouse DL, Burnett RT, Chen H, Weichenthal S, Johnson M, Villeneuve PJ, Walker M (2016) Ambient air pollution and adverse birth outcomes: differences by maternal comorbidities. Environ Res 148:457–466

    Article  CAS  Google Scholar 

  • Liu S, Krewski D, Shi Y, Chen Y, Burnett RT (2003) Association between gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver, Canada. Environ Health Perspect 111(14):1773–1778

    Article  CAS  Google Scholar 

  • Malley CS, Kuylenstierna JC, Vallack HW, Henze DK, Blencowe H, Ashmore MR (2017) Preterm birth associated with maternal fine particulate matter exposure: a global, regional and national assessment. Environ Int 101:173–182

    Article  Google Scholar 

  • Mayhew TM (2009) A stereological perspective on placental morphology in normal and complicated pregnancies. J Anat 215(1):77–90

    Article  Google Scholar 

  • McElrath TF, Lim KH, Pare E, Rich-Edwards J, Pucci D, Troisi R, Parry S (2012) Longitudinal evaluation of predictive value for preeclampsia of circulating angiogenic factors through pregnancy. Am J Obstet Gynecol 207(5):407.e401–407.e407

    Article  Google Scholar 

  • Melody SM, Ford J, Wills K, Venn A, Johnston FH (2019) Maternal exposure to short-to medium-term outdoor air pollution and obstetric and neonatal outcomes: a systematic review. Environ Pollut 244:915–925

    Article  CAS  Google Scholar 

  • Mirowsky J, Gordon T (2015) Noninvasive effects measurements for air pollution human studies: methods, analysis, and implications. J Expo Sci Environ Epidemiol 25:354–380

    Article  Google Scholar 

  • Nobles CJ, Grantz KL, Liu D, Williams A, Ouidir M, Seeni I, Sherman S, Mendola P (2019) Ambient air pollution and fetal growth restriction: physician diagnosis of fetal growth restriction versus population-based small-for-gestational age. Sci Total Environ 650(Pt 2):2641–2647

    Article  CAS  Google Scholar 

  • Novaes P, do Nascimento Saldiva PH, Kara-José N, Macchione M, Matsuda M, Racca L, Berra A (2007) Ambient levels of air pollution induce goblet-cell hyperplasia in human conjunctival epithelium. Environ Health Perspect 115(12):1753–1756

    Article  CAS  Google Scholar 

  • Olmo NR, Saldiva PH, Braga AL, Lin CA, Santos UEP, Pereira LA (2011) A review of low-level air pollution and adverse effects on human health: implications for epidemiological studies and public policy. Clinics (Sao Paulo) 66(4):681–690

    Article  Google Scholar 

  • Olsson D, Mogren I, Forsberg B (2013) Air pollution exposure in early pregnancy and adverse pregnancy outcomes: a register-based cohort study. BMJ Open 3(2):e001955

    Article  Google Scholar 

  • Pedersen M, Giorgis-Allemand L, Bernard C, Aguilera I, Andersen AM, Ballester F, Beelen RM, Chatzi L, Cirach M, Danileviciute A, Dedele A, Eijsden M, Estarlich M, Fernández-Somoano A, Fernández MF, Forastiere F, Gehring U, Grazuleviciene R, Gruzieva O, Heude B, Hoek G, de Hoogh K, van den Hooven EH, Håberg SE, Jaddoe VW, Klümper C, Korek M, Krämer U, Lerchundi A, Lepeule J, Nafstad P, Nystad W, Patelarou E, Porta D, Postma D, Raaschou-Nielsen O, Rudnai P, Sunyer J, Stephanou E, Sørensen M, Thiering E, Tuffnell D, Varró MJ, Vrijkotte TG, Wijga A, Wilhelm M, Wright J, Nieuwenhuijsen MJ, Pershagen G, Brunekreef B, Kogevinas M, Slama R (2013) Ambient air pollution and low birthweight: a European cohort study (ESCAPE). Lancet Respir Med 1(9):695–704

    Article  CAS  Google Scholar 

  • Pedersen M, Stayner L, Slama R, Sørensen M, Figueras F, Nieuwenhuijsen MJ, Raaschou-Nielsen O, Dadvand P (2014) Ambient air pollution and pregnancy-induced hypertensive disorders: a systematic review and meta-analysis. Hypertension 64(3):494–500

    Article  CAS  Google Scholar 

  • Phipps EA, Thadhani R, Benzing T, Karumanchi SA (2019) Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol 15(5):275–289

    Article  Google Scholar 

  • Poon LC and Nicolaides KH (2019). First-trimester maternal factors and biomarker screening for preeclampsia - Poon - 2014 - Prenatal Diagnosis - Wiley Online Library.

  • Romão R, Pereira LA, Saldiva PH, Pinheiro PM, Braga AL, Martins LC (2013) The relationship between low birth weight and exposure to inhalable particulate matter. Cad Saude Publica 29(6):1101–1108

    Article  Google Scholar 

  • Sapkota A, Chelikowsky AP, Nachman KE, Cohen AJ, Ritz B (2012) Exposure to particulate matter and adverse birth outcomes: a comprehensive review and meta-analysis. Air Qual Atmos Health 5(4):369–381

    Article  CAS  Google Scholar 

  • Schuch D, de Freitas ED, Espinosa SI, Martins LD, Carvalho VSB, Ramin BF, Silva JS, Martins JA, de Fatima Andrade M (2019) A two decades study on ozone variability and trend over the main urban areas of the São Paulo state, Brazil. Environ Sci Pollut Res Int 26(31):31699–31716

    Article  CAS  Google Scholar 

  • Shah PS, Balkhair T, Knowledge Synthesis Group on Determinants of Preterm/LBW births (2011) Air pollution and birth outcomes: a systematic review. Environ Int 37(2):498–516

    Article  CAS  Google Scholar 

  • Sircar M, Thadhani R, Karumanchi SA (2015) Pathogenesis of preeclampsia. Curr Opin Nephrol Hypertens 24(2):131–138

    Article  CAS  Google Scholar 

  • Steinle S, Reis S, Sabel CE (2013) Quantifying human exposure to air pollution--moving from static monitoring to spatio-temporally resolved personal exposure assessment. Sci Total Environ 443:184–193

    Article  CAS  Google Scholar 

  • Sundrani D, Khot V, Pisal H, Mehendale S, Wagh G, Joshi A, Joshi S (2013) Gestation dependant changes in angiogenic factors and their associations with fetal growth measures in normotensive pregnancy. PLoS One 8:e54153

    Article  CAS  Google Scholar 

  • van den Hooven EH, de Kluizenaar Y, Pierik FH, Hofman A, van Ratingen SW, Zandveld PY, Mackenbach JP, Steegers EA, Miedema HM, Jaddoe VW (2011) Air pollution, blood pressure, and the risk of hypertensive complications during pregnancy: the generation R study. Hypertension 57(3):406–412

    Article  Google Scholar 

  • van den Hooven EH, Pierik FH, de Kluizenaar Y, Hofman A, van Ratingen SW, Zandveld PY, Russcher H, Lindemans J, Miedema HM, Steegers EA, Jaddoe VW (2012) Air pollution exposure and markers of placental growth and function: the generation R study. Environ Health Perspect 120(12):1753–1759

    Article  Google Scholar 

  • Veras MM, Damaceno-Rodrigues NR, Caldini EG, Maciel Ribeiro AA, Mayhew TM, Saldiva PH, Dolhnikoff M (2008) Particulate urban air pollution affects the functional morphology of mouse placenta. Biol Reprod 79(3):578–584

    Article  CAS  Google Scholar 

  • Yorifuji T, Naruse H, Kashima S, Murakoshi T, Doi H (2015) Residential proximity to major roads and obstetrical complications. Sci Total Environ 508:188–192

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge Companhia Ambiental do Estado de São Paulo (CETESB).

Funding

This work was financed by grants 2008/57717-6, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), and part of notice 15 CNPq/Fapesp – (Instituto Nacional de Análise de Risco Ambiental) INAIRA, case number 2009/17315-9. Both were for financial support.

Author information

Authors and Affiliations

  1. Disciplina de Obstetricia, Departamento de Obstetricia e Ginecologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil

    Karen Hettfleisch, Luciana Duzolina Manfré Pastro, Rossana Pulcineli Vieira Francisco & Lisandra Stein Bernardes

  2. Divisao de Clinica Obstetrica, Hospital das Clinicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil

    Mariana Azevedo Carvalho

  3. LIM 57 Laboratorio de Fisiologia Obstetrica, Hospital das Clinicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, Brazil

    Mara Sandra Hoshida

  4. Instituto de Saude da Secretaria do Estado da Saude/SES-SP, São Paulo, Brazil

    Silvia Regina Dias Medici Saldiva

  5. Departamento de Pediatria, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, São Paulo, Brazil

    Sandra Elisabete Vieira

  6. Departamento de Patologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil

    Paulo Hilário Nascimento Saldiva

Authors
  1. Karen Hettfleisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mariana Azevedo Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mara Sandra Hoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luciana Duzolina Manfré Pastro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Silvia Regina Dias Medici Saldiva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sandra Elisabete Vieira
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rossana Pulcineli Vieira Francisco
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Paulo Hilário Nascimento Saldiva
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lisandra Stein Bernardes
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Karen Hettfleisch, Mariana Azevedo Carvalho, Mara Sandra Hoshida, Luciana Duzolina Manfré Pastro, Silvia R D M Saldiva, Sandra Elisabete Vieira, Rossana Pulcineli Vieira Francisco, Paulo Hilário Nascimento Saldiva, and Lisandra Stein Bernardes. The first draft of the manuscript was written by Karen Hettfleisch and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Lisandra Stein Bernardes.

Ethics declarations

Ethics approval and consent to participate

The research project was approved by the Ethics and Research Committee of the São Paulo University Medical School, São Paulo, Brazil, under reference number 132/10 and by the Ethics and Research Committee of the Municipal Health Secretariat of the City of São Paulo under CAAE number: 0205.0.162.162-10, reference number 430/10. Pregnant women were invited to participate in the study and those who accepted signed an Informed Consent Form.

Consent to publish

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Responsible Editor: Lotfi Aleya

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hettfleisch, K., Carvalho, M.A., Hoshida, M.S. et al. Individual exposure to urban air pollution and its correlation with placental angiogenic markers in the first trimester of pregnancy, in São Paulo, Brazil. Environ Sci Pollut Res 28, 28658–28665 (2021). https://doi.org/10.1007/s11356-021-12353-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-021-12353-7

Keywords

Search

Navigation