Perinatal maternal smoking exposure (PMSE) is one of the major environmental risk factors encountered by the fetus. PMSE is usually associated with adverse pregnancy outcomes that may manifest at different stages of life. Nevertheless, fetal growth restriction is the most common smoking-induced side effect. PMSE induces changes in the maternal multiple organ systems. These alterations may affect placentation, which subsequently affects fetal growth. It is worthy to note, however, that the extent of maternal smoking-induced changes depends mainly on the maternal level of susceptibility. Hence, the perinatal pregnancy outcomes vary depending on the interaction between the triad: the maternal, fetal, and placental modifications, making it more complex. In this review, we try to unveil the effect of smoking-induced maternal changes on the maternal immune, endocrine, and metabolic pathways and their impact on fetal growth.

Keywords:
Smoking, Fetal growth restriction, Immune system, Endocrine system, Metabolic system, Pregnancy, Placenta
1.
Unterscheider J, O'Donoghue K, Daly S, Geary MP, Kennelly MM, McAuliffe FM, Hunter A, Morrison JJ, Burke G, Dicker P, Tully EC, Malone FD: Fetal growth restriction and the risk of perinatal mortality-case studies from the multicentre PORTO study. BMC Pregnancy Childbirth 2014;14:63.
2.
Jang DG, Jo YS, Lee SJ, Kim N, Lee GS: Perinatal outcomes and maternal clinical characteristics in IUGR with absent or reversed end-diastolic flow velocity in the umbilical artery. Arch Gynecol Obstet 2011;284:73-78.
3.
Seaton SE, Yadav KD, Field DJ, Khunti K, Manktelow B: Birthweight centile charts for South Asian infants born in the UK. Neonatology 2011;100:398-403.
4.
Cosmi E, Fanelli T, Visentin S, Trevisanuto D, Zanardo V: Consequences in infants that were intrauterine growth restricted. J Pregnancy DOI: 10.1155/2011/36438.
5.
Kirkland SA, Dodds LA, Brosky G: The natural history of smoking during pregnancy among women in Nova Scotia. CMAJ 2000;163:281-282.
6.
Sureda X, Martínez-Sánchez JM, Fu M, Pérez-Ortuño R, Martínez C, Carabasa E, López M J, Saltó E, Pascual JA, Fernández E: Impact of the Spanish smoke-free legislation on adult, non-smoker exposure to secondhand smoke: cross-sectional surveys before (2004) and after (2012) legislation. PLoS One 2014;9:e89430.
7.
Chapman SLC, Wu L: E-cigarette prevalence and correlates of use among adolescents versus adults. J Psychiatr Res 2014;54:43-54.
8.
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.
9.
Berlin I, Heilbronner C, Georgieu S, Meier C, Spreux-Varoquaux O: Newborns' cord blood plasma cotinine concentrations are similar to that of their delivering smoking mothers. Drug Alcohol Depend 2010;107:250-252.
10.
Luck W, Nau H, Hansen R, Steldinger R: Extent of nicotine and cotinine transfer to the human fetus, placenta and amniotic fluid of smoking mothers. Dev Pharmacol Ther 1985;8:384-395.
11.
Pastrakuljic A, Schwartz R, Simone C, Derewlany LO, Knie B, Koren G: Transplacental transfer and biotransformation studies of nicotine in the human placental cotyledon perfused in vitro. Life Sci 1998;63:2333-2342.
12.
Puig C, Vall O, García-Algar Ó, Papaseit E, Pichini S, Saltó E, Villalb JR: Assessment of prenatal exposure to tobacco smoke by cotinine in cord blood for the evaluation of smoking control policies in Spain. BMC 2012;12:26.
13.
Kharrazi M, DeLorenze GN, Kaufman FL, Eskenazi B, Bernert JT, Graham S, Pearl M, Pirkle J: Environmental tobacco smoke and pregnancy outcome. Epidemiology 2004;15:660-670.
14.
Chandra S, Tripathi AK, Mishra S, Amzarul M, Vaish AK: Physiological changes in hematological parameters during pregnancy. Indian J Hematol Blood Transfus 2012;28:144-146.
15.
Saito S, Nakashima A, Shima T, Ito M: Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol 2010;63:601-610.
16.
Prins JR, Hylkema MN, Erwich JJ, Huitema S, Dekkema GJ, Dijkstra FE, Faas MM, Melgert BN: Smoking during pregnancy influences the maternal immune response in mice and humans. Am J Obstet Gynecol 2012;207:76.
17.
Athanassakis I, Vassiliadis S: Interplay between T helper type 1 and type 2 cytokines and soluble major histocompatibility complex molecules: a paradigm in pregnancy. Immunology 2002;107:281-287.
18.
Duriez M, Quillay H, Madec Y, El Costa H, Cannou C, Marlin R, de Truchis C, Rahmati M, Barré-Sinoussi F, Nugeyre MT, Menu E: Human decidual macrophages and NK cells differentially express Toll-like receptors and display distinct cytokine profiles upon TLR stimulation. Front Microbiol 2014;5:316.
19.
Mian MF, Lauzon NM, Stämpfli MR, Mossman KL, Ashkar AA: Impairment of human NK cell cytotoxic activity and cytokine release by cigarette smoke. J Leukoc Biol 2008;83:774-784.
20.
Luppi P, Lain K, Jeyabalan A, DeLoia J: The effects of cigarette smoking on circulating maternal leukocytes during pregnancy. Clin Immunol 2007;122:214-219.
21.
Thorley AJ, Tetley TD: Pulmonary epithelium, cigarette smoke, and chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2007;2:409-428.
22.
Miller EC, Cao H, Wen SW, et al: The risk of adverse pregnancy outcomes is increased in preeclamptic women who smoke compared with nonpreeclamptic women who do not smoke. Am J Obstet Gynecol 2010;203:334.
23.
Wei J, Liu CX, Gong TT, Wu QJ, Wu L: Cigarette smoking during pregnancy and preeclampsia risk: a systematic review and meta-analysis of prospective studies. Oncotarget 2015;41:43667-43678.
24.
Llurba E, Sánchez O, Domínguez C, Soro G, Goya M, Alijotas-Reig J, Cabero L: Smoking during pregnancy: changes in mid-gestation angiogenic factors in women at risk of developing preeclampsia according to uterine artery Doppler findings. Hypertens Pregnancy 2013;32:50-59.
25.
Jeyabalan A, Powers RW, Durica AR, Harger GF, Roberts JM, Ness RB: Cigarette smoke exposure and angiogenic factors in pregnancy and preeclampsia. Am J Hypertens 2008;21:943-947.
26.
Bernstein L, Pike MC, Lobo RA, Depue RH, Ross RK, Henderson BE: Cigarette smoking in pregnancy results in marked decrease in maternal hCG and estradiol levels. Br J Obstet Gynaecol 1989;96:92-96.
27.
Piasek M, Blanuša M, Kostial K, Laskey JW: Placental cadmium and progesterone concentrations in cigarette smokers. Reprod Toxicol 2001;15:673-681.
28.
Varvarigou AA, Liatsis SG, Vassilakos P, Decavalas G, Beratis NG: Effect of maternal smoking on cord blood estriol, placental lactogen, chorionic gonadotropin, FSH, LH, and cortisol. J Perinat Med 2009;37:364-369.
29.
Fang F, Luo ZC, Dejemli A, Delvin E, Zhang J: Maternal smoking and metabolic health biomarkers in newborns. PLoS One 2015;23:10.
30.
Arneric SP: Neurobiology and clinical pathophysiology of neuronal nicotinic acetylcholine receptors; in Piasecki MP, Newhouse P (eds): Nicotine in Psychiatry: Psychopathology and Emerging Therapies. Washington, American Psychiatric Press, 2000, pp 3-35.
31.
Li Y, Gonzalez P, Zhanga L: Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions. Prog Neurobiol 2012;98:145-165.
32.
Behl M, Rao D, Aagaard K, Davidson TL, Levin ED, Slotkin TA, Srinivasan S, Wallinga D, White MF, Walker VR, Thayer KA, Holloway AC: Evaluation of the association between maternal smoking, childhood obesity, and metabolic disorders: a national toxicology program workshop review. Environ Health Perspect 2013;121:170-180.
33.
Figueras F, Gardosi J: Intrauterine growth restriction: new concepts in antenatal surveillance, diagnosis, and management. Am J Obstet Gynecol 2011;204:288-300.
34.
Baschat AA: Neurodevelopment following fetal growth restriction and its relationship with antepartum parameters of placental dysfunction. Ultrasound Obstet Gynecol 2011;37:501-514.
35.
Kovo M, Schreiber L, Ben-Haroush A, Cohen G, Weiner E, Golan A, Bar J: The placental factor in early- and late-onset normotensive fetal growth restriction. Placenta 2013;34:320-324.
36.
Blumenthal I: Carbon monoxide poisoning. J R Soc Med 2001;94:270-272.
37.
Sun X, Xu H, Meng X, Qi J, Cui Y, Li Y, Zhang H, Xu L: Potential use of hyperoxygenated solution as a treatment strategy for carbon monoxide poisoning. PLoS One 2013;8:e81779.
38.
Thompson J, Bannigan J: Cadmium: toxic effects on the reproductive system and the embryo. Reprod Toxicol 2008;25:304-315.
39.
Kippler M, Hoque AM, Raqib R, Öhrvik H, Ekström EC, Vahter M: Accumulation of cadmium in human placenta interacts with the transport of micronutrients to the fetus. Toxicol Lett 2010;192:162-168.
40.
Kuhnert PM, Kuhnert BR, Erhard P, Brashear WT, Groh-Wargo SL, Webster S: The effect of smoking on placental and fetal zinc status. Am J Obstet Gynecol 1987;157:1241-1246.
41.
Burton GJ, Palmer ME, Dalton KJ: Morphometric differences between the placental vasculature of non-smokers, smokers and ex-smokers. BJOG 1989;96:907.
42.
Genbacev O, McMaster MT, Lazic J: Concordant in situ and in vitro data show that maternal cigarette smoking negatively regulates placental cytotrophoblast passage through the cell cycle. Reprod Toxicol 2000;14:495-506.
43.
Pastrakuljic A, Derewlany LO, Koren G: Maternal cocaine use and cigarette smoking in pregnancy in relation to amino acid transport and fetal growth. Placenta 1999;20:499-512.
44.
Velicky P, Knöfler M, Pollheimer J: Function and control of human invasive trophoblast subtypes: intrinsic vs. maternal control. Cell Adh Migr 2016;10:154-162.
45.
Monica G, Lilja C: Placenta previa, maternal smoking and recurrence risk. Acta Obstet Gynecol Scand 1995;74:341-345.
46.
Metzger MJ, Halperin AC, Manhart LE, Hawes SE: Association of maternal smoking during pregnancy with infant hospitalization and mortality due to infectious diseases. Pediatr Infect Dis J 2013;32:e1-e7.
47.
Zhang L, González-Chica DA, Cesar JA, Mendoza-Sassi RA, Beskow B, Larentis N, Blosfeld T: Maternal smoking during pregnancy and anthropometric measurements of newborns: a population-based study. Cad Saude Publica 2011;27:1768-1776.
48.
England LJ, Kendrick JS, Wilson HG, Merritt RK, Gargiullo PM, Zahniser SC: Effects of smoking reduction during pregnancy on the birth weight of term infants. Am J Epidemiol 2001;154:694-701.
49.
Anblagan D, Jones NW, Costigan C, Parker AJJ, Allcock K, Aleong R, Coyne LH, Deshpande R, Fenning NR, Bugg G, Roberts N, Pausova Z, Paus T, Gowland PA: Maternal smoking during pregnancy and fetal organ growth: a magnetic resonance imaging study. PLoS One 2013;8:e67223.
50.
Bernstein IM, Mongeon JA, Badger GJ, Solomon L, Heil SH, Higgins ST: Maternal smoking and its association with birth weight. Obstet Gynecol 2005;106:986-991.
51.
Cnattingius S, Haglund B: Decreasing smoking prevalence during pregnancy in Sweden: the effect on small-for-gestational-age births. Am J Public Health 1997;87:410-413.
52.
Teixeira JM, Fisk NM, Glover V: Association between maternal anxiety in pregnancy and increased uterine artery resistance index: cohort based study. BMJ 1999;318:153-157.
53.
Coppens M, Vindla S, James DK, Sahota DS: Computerized analysis of acute and chronic changes in fetal heart rate variation and fetal activity in association with maternal smoking. Am J Obstet Gynecol 2001;185:421-426.
54.
Müller JS, Antunes M, Behle I, Teixeira L, Zielinsky P: Acute effects of maternal smoking on fetal-placental-maternal system hemodynamics. Arq Bras Cardiol 2002;78:148-155.
55.
Alzeidan RA, Mandil AA, Fayed AA, Wahabi HA: The effectiveness of breath carbon monoxide analyzer in screening for environmental tobacco smoke exposure in Saudi pregnant women. Ann Thorac Med 2013;8:214-217.
56.
Haug K, Irgens LM, Skjaerven R, Markestad T, Baste V, Schreuder P: Maternal smoking and birthweight: effect modification of period, maternal age and paternal smoking. Acta Obstet Gynecol Scand 2000;79:485-489.
57.
Salihu HM, Shumpert MN, Aliyu MH, Kirby RS, Alexander GR: Smoking-associated fetal morbidity among older gravidas: a population study. Acta Obstet Gynecol Scand 2005;84:329-334.
58.
Wickström R: Effects of nicotine during pregnancy: human and experimental evidence. Curr Neuropharmacol 2007;5:213-222.
59.
Perry BL, Stevens-Watkins D, Oser CB: The moderating effects of skin color and ethnic identity affirmation on suicide risk among low-SES African American women. Race Soc Probl 2013;5:1-14.
60.
Hatagima A: Genetic polymorphisms and metabolism of endocrine disruptors in cancer susceptibility. Caud Saude Publica 2002;18:357-377.
61.
Cnattingius S: The epidemiology of smoking during pregnancy: smoking prevalence, maternal characteristics, and pregnancy outcomes. Nicotine Tobacco Res 2004;6(suppl 2):S125-S140.
62.
Jaddoe VW, Troe EJ, Hofman A, Mackenbach JP, Moll HA, Steegers EA, et al: Active and passive maternal smoking during pregnancy and the risks of low birthweight and preterm birth: the Generation R Study. Paediatr Perinat Epidemiol 2008;22:162-171.
63.
Andres RL, Day MC: Perinatal complications associated with maternal tobacco use. Semin Neonatol 2000;5:231-241.
64.
Sieminska A, Jassem E: The many faces of tobacco use among women. Med Sci Monit 2014;20:153-162.
65.
George L, Granath F, Johansson AL, Anneren G, Cnattingius S: Environmental tobacco smoke and risk of spontaneous abortion. Epidemiology 2006;17:500-505.
66.
Pijpers L, Wladimiroff JW, McGhie JS, Bom N: Acute effect of maternal smoking on the maternal and fetal cardiovascular system. Early Hum Dev 1984;10:95-105.
67.
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.
68.
Kuehl KS, Loffredo CA: Population-based study of transposition of the great arteries: possible associations with environmental factors. Birth Defects Res A Clin Mol Teratol 2003;67:162-167.
69.
Carmichael SL, Ma C, Rasmussen SA, Honein MA, Lammer EJ, Shaw GM; National Birth Defects Prevention Study: Craniosynostosis and maternal smoking. Birth Defects Res A Clin Mol Teratol 2008;82:78-85.
70.
Al Mamun A, Lawlor DA, Alati R, O'Callaghan MJ, Williams GM, Najman JM: Does maternal smoking during pregnancy have a direct effect on future offspring obesity? Evidence from a prospective birth cohort study. Am J Epidemiol 2006;164:317-325.
71.
Key APF, Ferguson M, Molfese DL, Peach K, Lehman C, Molfese VJ: Smoking during pregnancy affects speech-processing ability in newborn infants. Environ Health Perspect 2007;115:623-629.
72.
Knopik VS: Maternal smoking during pregnancy and child outcomes: real or spurious effect? Dev Neuropsychol 2009;34:1-36.
73.
Bernhard D, Csordas A, Henderson B, Rossmann A, Kind M, Wick G: Cigarette smoke metal-catalyzed protein oxidation leads to vascular endothelial cell contraction by depolymerization of microtubules. FASEB J 2005;19:1096-1107.
74.
Kiowski W, Linder L, Stoschitzky K, Pfisterer M, Burckhardt D, Burkart F, Bühler FR: Diminished vascular response to inhibition of endothelium-derived nitric oxide and enhanced vasoconstriction to exogenously administered endothelin-1 in clinically healthy smokers. Circulation 1994;90:27-34.
75.
Salahuddin S, Prabhakaran D, Roy A: Pathophysiological mechanisms of tobacco-related CVD. Glob Heart 2012;7:113-120.
76.
Alberg AJ, Shopland DR, Cummings KM: The 2014 Surgeon General's report: commemorating the 50th Anniversary of the 1964 Report of the Advisory Committee to the US Surgeon General and updating the evidence on the health consequences of cigarette smoking. Am J Epidemiol 2014;179:403-412.
77.
Lawlor DA, Najman JM, Sterne J, Williams GM, Ebrahim S, Smith GD: Associations of parental, birth, and early life characteristics with systolic blood pressure at 5 years of age. Findings from the Mater-University study of pregnancy and its outcomes. Circulation 2004;110:2417-2423.
78.
Brion MJ, Leary SD, Smith GD, Ness AR: Similar associations of parental prenatal smoking suggest childhood blood pressure is not influenced by intrauterine effects. Hypertension 2007;49:1422-1428.
79.
Power C, Atherton K, Thomas C: Maternal smoking in pregnancy, adult adiposity and other risk factors for cardiovascular disease. Atherosclerosis 2010;211:643-648.
80.
Jaddoe VWV, Ridder MAJ, Van Elzen APM, Hofman A, Uiterwaal CSPM, Witteman JCM: Maternal smoking is associated with cholesterol development in the offspring: a 27 years follow-up study. Atherosclerosis 2008;196:42-48.
81.
Geerts CC, Bots ML, Grobbee DE, Uiterwaal CS: Parental smoking and vascular damage in young adult offspring: is early life exposure critical? The atherosclerosis risk in young adults study. Arterioscler Thromb Vasc Boil 2008;28:2296-2302.
82.
Geelhoed JJ, El Marroun H, Verburg BO, van Osch-Gevers L, Hofman A, Huizink AC, Moll HA, Verhulst FC, Helbing WA, Steegers EA, Jaddoe VW: Maternal smoking during pregnancy, fetal arterial resistance adaptations and cardiovascular function in childhood. BJOG 2011;118:755-762.
83.
Schoendorf KC, Kiely JL: Relationship of sudden infant death syndrome to maternal smoking during and after pregnancy. Pediatrics 1992;90:905-908.
84.
Yolton K, Dietrich K, Auinger P, Lanphear BP, Hornung R: Exposure to environmental tobacco smoke and cognitive abilities among U.S. children and adolescents. Environ Health Perspect 2005;113:98-103.
85.
Dietz PM, Homa D, England LJ, Burley K, Tong VT, Dube SR: Estimates of nondisclosure of cigarette smoking among pregnant and nonpregnant women of reproductive age in the United States. Am J Epidemiology 2011;173:355-359.
86.
Benowitz NL: Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev 1996;18:188-204.
87.
Seybold DJ, Broce M, Siegel E, Findley J, Calhoun BC: Smoking in pregnancy in West Virginia: does cessation/reduction improve perinatal outcomes? Matern Child Health J 2012;16:133-138.
88.
Salihu HM, Wilson RE: Epidemiology of prenatal smoking and perinatal outcomes. Early Hum Dev 2007;83:713-720.
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