Smoking and Pregnancy — A Review on the First Major Environmental Risk Factor of the Unborn
Abstract
:1. Introduction
2. Epidemiology and Risk Factors
3. Decreased Fertility and Pregnancy Complications Due to Smoking
Pregnancy complication | ARR | OR | CI (95%) |
---|---|---|---|
Preterm rupture of membrane | 1.67 | 1.43–1.96 | |
Chorioamnionitis | 1.65 | 1.36–2.00 | |
Incompetent cervix | 1.63 | 1.35–1.96 | |
Threatened premature delivery | 1.38 | 1.17–1.64 | |
Placental abruption | 1.37 | 1.10–1.72 | |
Pregnancy-induced hypertension | 1.20 | 1.01–1.41 | |
Stillbirth | 1.23 | 1.09–1.38 |
4. Biochemical Changes and Alterations
5. Smoking and Intrauterine Growth Retardation
6. Alterations in the Genetic and Cellular Level
7. Diseases Caused by Smoking during Pregnancy
7.1. Heart Diseases and Cardiovascular Diseases
Congenital heart defect | RR | OR | CI (95%) | n |
---|---|---|---|---|
Congenital heart defects (total) | 1.11 | 1.09 | 1.02–1.21 | 18,282 |
Septal heart defects | 1.44 | 1.16–1.79 | 2,977 | |
Secundum-type atrial septal defects | 1.36 | 1.04–1.78 | ||
Right ventricular outflow tract defects | 1.32 | 1.06–1.65 | ||
Pulmonary valve stenosis | 1.35 | 1.05–1.74 | ||
Truncus arteriosus | 1.90 | 1.04–3.45 | ||
Transposition of the great arteries | 1.79 | 1.04–3.10 |
7.2. Hypertension and Kidney Diseases
7.3. Pulmonary Diseases
7.4. Gastrointestinal Diseases
8. BMI and Obesity
9. Alterations in Neurology and Psychological Behavior
10. Addiction
11. Therapy and Anti-Smoking Programs
12. Conclusions
Conflicts of Interest
References
- Higgins, S.T.; Washio, Y.; Heil, S.H.; Solomon, L.J.; Gaalema, D.E.; Higgins, T.M.; Bernstein, I.M. Financial incentives for smoking cessation among pregnant and newly postpartum women. Prev. Med. 2011, 55, S33–S40. [Google Scholar]
- Bickerstaff, M.; Beckmann, M.; Gibbons, K.; Flenady, V. Recent cessation of smoking and its effect on pregnancy outcomes. Aust. N. Z. J. Obstet. Gynaecol. 2012, 52, 54–58. [Google Scholar] [CrossRef]
- El-Mohandes, A.A.; El-Khorazaty, M.N.; Kiely, M.; Gantz, M.G. Smoking cessation and relapse among pregnant African-American smokers in Washington, DC. Matern. Child Health J. 2011, 15, S96–S105. [Google Scholar] [CrossRef]
- Dudenhausen, J.W. Rauchen in der Schwangerschaft—Häufigkeit; (in German). Urban und Vogel: Munich, Germany, 2009. [Google Scholar]
- Knut-Olaf, H.; Groneberg, D. Tabakabhängigkeit—Gesundheitliche Schäden durch das Rauchen; (in German). Springer Verlag: Berlin, Germany, 2008. [Google Scholar]
- Thäle, V.; Schlitt, A. Effects of alcohol and smoking in pregnancy. Internist 2011, 52, 1185–1190. [Google Scholar] [CrossRef]
- Simmons, V.N.; Cruz, L.M.; Brandon, T.H.; Quinn, G.P. Translation and adaptation of smoking relapse-prevention materials for pregnant and postpartum Hispanic women. J. Health Commun. 2011, 16, 90–107. [Google Scholar]
- Rauchen Während Der Schwangerschaft Oder Niedriger Sozialstatus. Available online: https://www.thieme-connect.com/ejournals/abstract/10.1055/s-2001-18366 (accessed on 5 October 2013).
- Rauchen in der Schwangerschaft. Available online: http://www.stern.de/gesundheit/gesundheitsnews/rauchen-in-der-schwangerschaft-gewuerzgurken-und-glimmstaengel-608001.html (accessed on 5 October 2013).
- Dittrich, R.; Schibel, A.; Hoffmann, I.; Mueller, A.; Beckmann, M.W.; Cupisti, S. Influence of maternal smoking during pregnancy on oxidant status in amniotic fluid. In Vivo 2012, 26, 813–818. [Google Scholar]
- Page, R.L.; Padilla, Y.C.; Hamilton, E.R. Psychosocial factors associated with patterns of smoking surrounding pregnancy in fragile families. Matern. Child Health J. 2012, 16, 249–257. [Google Scholar] [CrossRef]
- Thrift, A.P.; Nancarrow, H.; Bauman, A.E. Maternal smoking during pregnancy among aboriginal women in New South Wales is linked to social gradient. Aust. N. Z. J. Public Health 2011, 35, 337–342. [Google Scholar] [CrossRef]
- Agopian, A.J.; Lupo, P.J.; Herdt-Losavio, M.L.; Langlois, P.H.; Rocheleau, C.M.; Mitchell, L.E.; National birth defects prevention study. Differences in folic acid use, prenatal care, smoking, and drinking in early pregnancy by occupation. Prev. Med. 2012, 55, 341–345. [Google Scholar] [CrossRef]
- Batista, J.; Albuquerque, M.F.; Ximenes, R.A.; Miranda-Filho, D.B.; Melo, H.R.; Maruza, M.; Moura, L.V.; Ferraz, E.J.; Rodrigues, L.C. Prevalence and socioeconomic factors associated with smoking in people living with HIV by sex, in Recife, Brazil. Rev. Bras. Epidemiol. 2013, 16, 432–443. [Google Scholar] [CrossRef]
- O’Callaghan, F.V.; O’Callaghan, M.; Najman, J.M.; Williams, G.M.; Bor, W.; Alati, R. Prediction of adolescent smoking from family and social risk factors at 5 years, and maternal smoking in pregnancy and at 5 and 14 years. Addiction 2006, 101, 282–290. [Google Scholar] [CrossRef]
- Muckle, G.; Laflamme, D.; Gagnon, J.; Boucher, O.; Jacobson, J.L.; Jacobson, S.W. Alcohol, smoking, and drug use among Inuit women of childbearing age during pregnancy and the risk to childre. Alcohol. Clin. Exp. Res. 2011, 35, 1081–1091. [Google Scholar] [CrossRef]
- Foley, K.L.; Balázs, P.; Grenczer, A.; Rákóczi, I. Factors associated with quit attempts and quitting among Eastern Hungarian women who smoked at the time of pregnancy. Cent. Eur. J. Public Health 2011, 19, 63–66. [Google Scholar]
- Murin, S.; Rafii, R.; Bilello, K. Smoking and smoking cessation in pregnancy. Clin. Chest. Med. 2011, 32, 75–91. [Google Scholar] [CrossRef]
- Ahluwawalia, I.B.; Grummer-Strawn, L.; Scanlon, K.S. Exposure to environmental tobacco smoke and birth outcome: Increased effects on pregnant women aged 30 years and older. Am. J. Epidemiol. 1997, 146, 42–47. [Google Scholar] [CrossRef]
- Ananth, C.V.; Savitz, D.A.; Luther, E.R. Maternal cigarette smoking as a risk factor for placental abruption, placenta previa, and uteine bleeding in pregnancy. Am. J. Epidemiol. 1996, 144, 881–889. [Google Scholar] [CrossRef]
- Cnattingius, S.; Axelsson, O.; Eklund, G.; Lindmark, G. Smoking, maternal age, and fetal growth. Obstet. Gynecol. 1985, 66, 449–452. [Google Scholar]
- Wang, X.; Tager, I.B.; Van Vunakis, H.; Speizer, F.E.; Hanrahan, J.P. Maternal smoking during pregnancy, urine cotinine concentrations, and birth outcomes. A prospective cohort study. Int. J. Epidemiol. 1997, 26, 978–988. [Google Scholar] [CrossRef]
- Hayashi, K.; Matsuda, Y.; Kawamichi, Y.; Shiozaki, A.; Saito, S. Smoking during pregnancy increases risks of various obstetric complications: A case-cohort study of the Japan Perinatal Registry Network database. J. Epidemiol. 2011, 21, 61–66. [Google Scholar] [CrossRef]
- Leonardi-Bee, J.; Britton, J.; Venn, A. Secondhand smoke and adverse fetal outcomes in nonsmoking pregnant women: A meta-analysis. Pediatrics 2011, 127, 734–741. [Google Scholar] [CrossRef]
- Chelchowska, M.; Ambroszkiewicz, J.; Gajewska, J.; Laskowska-Klita, T.; Leibschang, J. The effect of tobacco smoking during pregnancy on plasma oxidant and antioxidant status in mother and newborn. Eur. J. Obstet. Gynecol. Reprod. Biol. 2011, 155, 132–136. [Google Scholar] [CrossRef]
- Sahinli, A.S.; Marakoğlu, K.; Kiyici, A. Evaluation of the levels of oxidative stress factors and ischemia modified albumin in the cord blood of smoker and non-smoker pregnant women. J. Matern. Fetal Neonatal Med. 2012, 25, 1064–1068. [Google Scholar] [CrossRef]
- Suzuki, K.; Kondo, N.; Sato, M.; Tanaka, T.; Ando, D.; Yamagata, Z. Gender differences in the association between maternal smoking during pregnancy and childhood growth trajectories: Multilevel analysis. Int. J. Obes. 2011, 35, 53–59. [Google Scholar]
- Metzger, M.J.; Halperin, A.C.; Manhart, L.E.; Hawes, S.E. Association of maternal smoking during pregnancy with infant hospitalization and mortality due to infectious diseases. Pediatr. Infect. Dis. J. 2012, 32, e1–e7. [Google Scholar]
- Erickson, A.C.; Arbour, L.T. Heavy smoking during pregnancy as a marker for other risk factors of adverse birth outcomes: A population-based study in British Columbia, Canada. BMC Public Health 2012, 12, 102. [Google Scholar] [CrossRef]
- Prins, J.R.; Hylkema, M.N.; Erwich, J.J.; Huitema, S.; Dekkema, G.J.; Dijkstra, F.E.; Faas, M.M.; Melgert, B.N. Smoking during pregnancy influences the maternal immune response in mice and humans. Am. J. Obstet. Gynecol. 2012, 207, 76.e1–76.e14. [Google Scholar] [CrossRef]
- Titova, O.E.; Ayvazova, E.A.; Bichkaeva, F.A.; Brooks, S.J.; Chumakova, G.N.; Schiöth, H.B.; Benedict, C. The influence of active and passive smoking during pregnancy on umbilical cord blood levels of vitamins A and E and neonatal anthropometric indices. Br. J. Nutr. 2012, 108, 1341–1345. [Google Scholar] [CrossRef]
- Tyrrell, J.; Huikari, V.; Christie, J.T.; Cavadino, A.; Bakker, R.; Brion, M.J.; Geller, F.; Paternoster, L.; Myhre, R.; Potter, C.; et al. Genetic variation in the 15q25 nicotinic acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4) interacts with maternal self-reported smoking status during pregnancy to influence birth weight. Hum. Mol. Genet. 2012, 21, 5344–5358. [Google Scholar] [CrossRef]
- Chertok, I.R.; Luo, J.; Anderson, R.H. Association between changes in smoking habits in subsequent pregnancy and infant birth weight in West Virginia. Matern. Child Health J. 2011, 15, 249–254. [Google Scholar] [CrossRef]
- Lelong, N.; Blondel, B.; Kaminski, M. Smoking during pregnancy in France between 1972 to 2003: Results from the national perinatal surveys. J. Gynecol. Obstet. Biol. Reprod. (Paris) 2011, 40, 42–49. [Google Scholar] [CrossRef]
- Pavić, I.; Dodig, S.; Jurković, M.; Krmek, T.; Spanović, D. The influence of mother’s active smoking during pregnancy on body mass index of newborns. Coll. Antropol. 2011, 35, 1149–1154. [Google Scholar]
- Lynch, C.M.; O’Kelly, R.; Stuart, B.; Treumann, A.; Conroy, R.; Regan, C.L. The role of thromboxane A(2) in the pathogenesis of intrauterine growth restriction associated with maternal smoking in pregnancy. Prostaglandins Other Lipid Mediat. 2011, 95, 63–67. [Google Scholar] [CrossRef]
- Zhang, L.; González-Chica, D.A.; Cesar, J.A.; Mendoza-Sassi, R.A.; Beskow, B.; Larentis, N.; Blosfeld, T. Maternal smoking during pregnancy and anthropometric measurements of newborns: A population-based study in southern of Brazil. Cad. Saude Publica 2011, 27, 1768–1776. [Google Scholar] [CrossRef]
- Joubert, B.R.; Håberg, S.E.; Nilsen, R.M.; Wang, X.; Vollset, S.E.; Murphy, S.K.; Huang, Z.; Hoyo, C.; Midttun, Ø.; Cupul-Uicab, L.A.; et al. 450K Epigenome-Wide Scan Identifies Differential DNA Methylation in Newborns Related to Maternal Smoking During Pregnancy. Environ. Health Perspect. 2012, 120, 1425–1431. [Google Scholar] [CrossRef]
- Allina, J.; Grabowski, J.; Doherty-Lyons, S.; Fiel, M.I.; Jackson, C.E.; Zelikoff, J.T.; Odin, J.A. Maternal allergy acts synergistically with cigarette smoke exposure during pregnancy to induce hepatic fibrosis in adult male offspring. J. Immunotoxicol. 2011, 8, 258–264. [Google Scholar] [CrossRef]
- Chehab, G.; El-Rassi, I.; Adhami, A.; Chokor, I.; Chatila, F.; Haddad, W.; Saliba, Z. Parental smoking during early pregnancy and congenital heart defects. J. Med. Liban. 2012, 60, 14–18. [Google Scholar]
- Alverson, C.J.; Strickland, M.J.; Gilboa, S.M.; Correa, A. Maternal smoking and congenital heart defects in the Baltimore-Washington Infant Study. Pediatrics 2011, 127, e647–e653. [Google Scholar] [CrossRef]
- Hackshaw, A.; Rodeck, C.; Boniface, S. Maternal smoking in pregnancy and birth defects: A systematic review based on 173 687 malformed cases and 11.7 million controls. Hum. Reprod. Update 2011, 17, 589–604. [Google Scholar] [CrossRef]
- Lee, L.J.; Lupo, P.J. Maternal Smoking During Pregnancy and the Risk of Congenital Heart Defects in Offspring: A Systematic Review and Metaanalysis. Pediatr. Cardiol. 2012, 34, 398–407. [Google Scholar] [CrossRef]
- Taal, H.R.; Geelhoed, J.J.; Steegers, E.A.; Hofman, A.; Moll, H.A.; Lequin, M.; van der Heijden, A.J.; Jaddoe, V.W. Maternal smoking during pregnancy and kidney volume in the offspring: The Generation R Study. Pediatr. Nephrol. 2011, 26, 1275–1283. [Google Scholar] [CrossRef]
- Søndergaard, C.; Henriksen, T.B.; Obel, C.; Wisborg, K. Smoking during pregnancy and infantile colic. Pediatrics 2001, 108, 342–346. [Google Scholar] [CrossRef]
- Matijasevich, A.; Brion, M.J.; Menezes, A.M.; Barros, A.J.; Santos, I.S.; Barros, F.C. Maternal smoking during pregnancy and offspring growth in childhood: 1993 and 2004 Pelotas cohort studies. Arch. Dis. Child 2011, 96, 519–525. [Google Scholar] [CrossRef]
- Mamun, A.A.; O’Callaghan, M.J.; Williams, G.M.; Najman, J.M. Maternal smoking during pregnancy predicts adult offspring cardiovascular risk factors - evidence from a community-based large birth cohort study. PLoS One 2012, 7, e41106. [Google Scholar]
- Raum, E.; Küpper-Nybelen, J.; Lamerz, A.; Hebebrand, J.; Herpertz-Dahlmann, B.; Brenner, H. Tobacco smoke exposure before, during, and after pregnancy and risk of overweight at age 6. Obesity 2011, 19, 2411–2417. [Google Scholar] [CrossRef]
- Durmus, B.; Kruithof, C.J.; Gillman, M.H.; Willemsen, S.P.; Hofman, A.; Raat, H.; Eilers, P.H.; Steegers, E.A.; Jaddoe, V.W. Parental smoking during pregnancy, early growth, and risk of obesity in preschool children: The Generation R Study. Am. J. Clin. Nutr. 2011, 94, 164–171. [Google Scholar] [CrossRef]
- Ino, T.; Shibuya, T.; Saito, K.; Inaba, Y. Relationship between body mass index of offspring and maternal smoking during pregnancy. Int. J. Obes. (Lond) 2012, 36, 554–558. [Google Scholar] [CrossRef]
- Koch, S.; Vilser, C.; Groß, W.; Schleußner, E. Smoking during pregnancy: Risk for intrauterine growth retardation and persisting microsomia. Z. Geburtshilfe Neonatol. 2012, 216, 77–81. [Google Scholar] [CrossRef]
- Wehby, G.L.; Prater, K.; McCarthy, A.M. The Impact of Maternal Smoking during Pregnancy on Early Child Neurodevelopment. J. Hum. Cap. 2011, 5, 207–254. [Google Scholar] [CrossRef]
- Bublitz, M.H.; Stroud, L.R. Maternal smoking during pregnancy and offspring brain structure and function: Review and agenda for future research. Nicotine Tob. Res. 2012, 14, 388–397. [Google Scholar] [CrossRef]
- Cents, R.A.; Bublitz, M.H.; Stroud, L.R. Maternal smoking during pregnancy and child emotional problems: The relevance of maternal and child 5-HTTLPR genotype. Am. J. Med. Genet. B Neuropsychiatr Genet. 2012, 159, 289–297. [Google Scholar]
- Larsson, M.; Montgomery, S.M. Maternal smoking during pregnancy and physical control and coordination among offspring. J. Epidemiol. Community Health 2011, 65, 1151–1158. [Google Scholar] [CrossRef]
- Heinonen, K.; Räikkönen, K.; Pesonen, A.K.; Andersson, S.; Kajantie, E.; Eriksson, J.G.; Wolke, D.; Lano, A. Longitudinal study of smoking cessation before pregnancy and children’s cognitive abilities at 56 months of age. Early Hum. Dev. 2011, 87, 353–339. [Google Scholar] [CrossRef]
- Piper, B.J.; Corbett, S.M. Executive function profile in the offspring of women that smoked during pregnancy. Nicotine Tob. Res. 2012, 14, 191–199. [Google Scholar] [CrossRef]
- Holbrook, A.M.; Kaltenbach, K.A. Effectiveness of a smoking cessation intervention for methadone-maintained women: A comparison of pregnant and parenting women. Int. J. Pediatr. 2011, 2011, 567056. [Google Scholar] [CrossRef]
- Buja, A.; Guarnieri, E.; Forza, G.; Tognazzo, F.; Sandonà, P.; Zampieron, A. Socio-demographic factors and processes associated with stages of change for smoking cessation in pregnant versus non-pregnant women. BMC Womens Health 2011, 11, 3. [Google Scholar] [CrossRef]
- Blalock, J.A.; Nayak, N.; Wetter, D.W.; Schreindorfer, L.; Minnix, J.A.; Canul, J.; Cinciripini, P.M. The relationship of childhood trauma to nicotine dependence in pregnant smokers. Psychol. Addict. Behav. 2011, 25, 652–663. [Google Scholar] [CrossRef]
- Wang, C.Y.; Kuo, S.C. Pregnancy and the struggle to quit smoking. Hu Li Za Zhi 2011, 58, 87–92. [Google Scholar]
- Eiden, R.D.; Leonard, K.E.; Colder, C.R.; Homish, G.G.; Schuetze, P.; Gray, T.R.; Huestis, M.A. Anger, hostility, and aggression as predictors of persistent smoking during pregnancy. J. Stud. Alcohol Drugs. 2011, 72, 926–932. [Google Scholar]
- Nguyen, S.N.; Von Kohorn, I.; Schulman-Green, D.; Colson, E.R. The importance of social networks on smoking: Perspectives of women who quit smoking during pregnancy. Matern. Child Health J. 2012, 16, 1312–1318. [Google Scholar] [CrossRef]
- Levine, M.D.; Cheng, Y.; Marcus, M.D.; Kalarchian, M.A. Relapse to smoking and postpartum weight retention among women who quit smoking during pregnancy. Obesity (Silver Spring) 2012, 20, 457–459. [Google Scholar] [CrossRef]
- Grover, K.W.; Zvolensky, M.J.; Lemeshow, A.R.; Galea, S.; Goodwin, R.D. Does quitting smoking during pregnancy have a long-term impact on smoking status? Drug. Alcohol Depend. 2012, 123, 110–114. [Google Scholar] [CrossRef]
- Herberts, C.; Sykes, C. Midwives’ perceptions of providing stop-smoking advice and pregnant smokers’ perceptions of stop-smoking services within the same deprived area of London. J. Midwifery Womens Health 2012, 57, 67–73. [Google Scholar] [CrossRef]
- Everett-Murphy, K.; Paijmans, J.; Steyn, K.; Matthews, C.; Emmelin, M.; Peterson, Z. Scolders, carers or friends: South African midwives’ contrasting styles of communication when discussing smoking cessation with pregnant women. Midwifery 2011, 27, 517–524. [Google Scholar] [CrossRef]
- Hemsing, N.; Greaves, L.; O’Leary, R.; Chan, K.; Okoli, C. Partner support for smoking cessation during pregnancy: A systematic review. Nicotine Tob. Res. 2012, 14, 767–776. [Google Scholar] [CrossRef]
- Windsor, R.; Woodby, L.; Miller, T.; Hardin, M. Effectiveness of Smoking Cessation and Reduction in Pregnancy Treatment (SCRIPT) methods in Medicaid-supported prenatal care: Trial III. Health Educ. Behav. 2011, 38, 412–422. [Google Scholar] [CrossRef]
- Fujioka, N.; Kobayashi, T.; Turale, S. Short-term behavioral changes in pregnant women after a quit-smoking program via e-learning: A descriptive study from Japan. Nurs. Health Sci. 2012, 14, 304–311. [Google Scholar] [CrossRef]
- Lauria, L.; Lamberti, A.; Grandolfo, M. Smoking behaviour before, during, and after pregnancy: The effect of breastfeeding. Sci. World J. 2012, 2012, 154910. [Google Scholar] [CrossRef]
- Xu, H.; Wen, L.M.; Rissel, C.; Baur, L.A. Smoking Status and Factors Associated with Smoking of First-Time Mothers During Pregnancy and Postpartum: Findings from the Healthy Beginnings Trial. Matern. Child Health J. 2012, 17, 1151–1157. [Google Scholar]
- Filion, K.B.; Abenhaim, H.A.; Mottillo, S.; Joseph, L.; Gervais, A.; O’Loughlin, J.; Paradis, G.; Pihl, R.; Pilote, L.; Rinfret, S. The effect of smoking cessation counselling in pregnant women: A meta-analysis of randomised controlled trials. BJOG 2011, 118, 1422–1428. [Google Scholar] [CrossRef]
- Cressman, A.M.; Pupco, A.; Kim, E.; Koren, G.; Bozzo, P. Smoking cessation therapy during pregnancy. Can. Fam. Physician 2012, 58, 525–527. [Google Scholar]
© 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Share and Cite
Mund, M.; Louwen, F.; Klingelhoefer, D.; Gerber, A. Smoking and Pregnancy — A Review on the First Major Environmental Risk Factor of the Unborn. Int. J. Environ. Res. Public Health 2013, 10, 6485-6499. https://doi.org/10.3390/ijerph10126485
Mund M, Louwen F, Klingelhoefer D, Gerber A. Smoking and Pregnancy — A Review on the First Major Environmental Risk Factor of the Unborn. International Journal of Environmental Research and Public Health. 2013; 10(12):6485-6499. https://doi.org/10.3390/ijerph10126485
Chicago/Turabian StyleMund, Mathias, Frank Louwen, Doris Klingelhoefer, and Alexander Gerber. 2013. "Smoking and Pregnancy — A Review on the First Major Environmental Risk Factor of the Unborn" International Journal of Environmental Research and Public Health 10, no. 12: 6485-6499. https://doi.org/10.3390/ijerph10126485
APA StyleMund, M., Louwen, F., Klingelhoefer, D., & Gerber, A. (2013). Smoking and Pregnancy — A Review on the First Major Environmental Risk Factor of the Unborn. International Journal of Environmental Research and Public Health, 10(12), 6485-6499. https://doi.org/10.3390/ijerph10126485