Develop a model for the study of Electronic Nicotine Device (ENDS) exposure on craniofacial development.
Design
Experimental preclinical design followed as pregnant murine dams were randomized and exposed to filtered air exposure, carrier exposure consisting of 50% volume of propylene glycol and vegetable glycine (ENDS Carrier) respectively, or carrier exposure with 20 mg/ml of nicotine added to the liquid vaporizer (ENDS carrier with nicotine).
Setting
Preclinical murine model exposure using the SciReq exposure system.
Participants
C57BL6 adult 8 week old female pregnant mice and exposed in utero litters.
Interventions
Exposure to control filtered air, ENDS carrier or ENDS carrier with nicotine added throughout gestation at 1 puff/minute, 4 h/day, five days a week.
Main Outcome Measures
Cephalometric measures of post-natal day 15 pups born as exposed litters.
Results
Data suggests alterations to several facial morphology parameters in the developing offspring, suggesting electronic nicotine device systems may alter facial growth if used during pregnancy.
Conclusions
Future research should concentrate on varied formulations and exposure regimens of ENDS to determine timing windows of exposures and ENDS formulations that may be harmful to craniofacial development.
BushAMHolsingerJWJr.PrybilLD. Employing the precautionary principle to evaluate the use of E-cigarettes. Front Public Health. 2016;4:5.
2.
LarsenPD. Vaping and adolescents: The next public health crisis. Rehabil Nurs. 2020;45(1):1‐2.
3.
RajuSVRoweSM. Not simply the lesser of two evils. Am J Physiol Lung Cell Mol Physiol. 2018;314(2):L236‐L238.
4.
WalleySCWilsonKMWinickoffJPGronerJ. A public health crisis: Electronic cigarettes, Vape, and JUUL. Pediatrics. 2019;143(6):e20182741.
5.
DuellAKPankowJFPeytonDH. Nicotine in tobacco product aerosols: ‘It's deja vu all over again’. Tob Control. 2020;29(6):656-662.
6.
WuJCRheeJWSallamK. Electronic cigarettes: Where there is smoke there is disease. J Am Coll Cardiol. 2019;74(25):3121‐3123.
7.
BesaratiniaATommasiS. Vaping epidemic: Challenges and opportunities. Cancer Causes Control. 2020;31(7):663‐667.
8.
CreamerMREverett JonesSGentzkeASJamalAKingBA. Tobacco product use among high school students - youth risk behavior survey, United States, 2019. MMWR Suppl. 2020;69(1):56‐63.
9.
HammondDWackowskiOAReidJLO'ConnorRJ. Use of JUUL E-cigarettes among youth in the United States. Nicotine Tob Res. 2020;22(5):827‐832.
10.
ParekhTDesaiR. A comparative analysis of E-cigarette users and state-specific prevalence change in the United States between 2017 and 2018. Cureus. 2020;12(12):e12079.
11.
WangGWuL. Healthy people 2020: Social determinants of cigarette smoking and electronic cigarette smoking among youth in the United States 2010–2018. Int J Environ Res Public Health. 2020;17(20):7503.
12.
CullenKAGentzkeASSawdeyMD, et al.e-cigarette use among youth in the United States, 2019. JAMA. 2019;322(21):2095-2103.
13.
WangTWGentzkeASCreamerMR, et al.Tobacco product use and associated factors among middle and high school students - United States, 2019. MMWR Surveill Summ. 2019;68(12):1‐22.
14.
CorneliusMEWangTWJamalALoretanCGNeffLJ. Tobacco product use among adults - United States, 2019. MMWR Morb Mortal Wkly Rep. 2020;69(46):1736‐1742.
15.
GentzkeASWangTWJamalA, et al.Tobacco product use among middle and high school students - United States, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(50):1881‐1888.
16.
MezaRJimenez-MendozaELevyDT. Trends in tobacco use among adolescents by grade, sex, and race, 1991–2019. JAMA Netw Open. 2020;3(12):e2027465.
17.
PearsonJLSharmaERuiN, et al.Association of electronic nicotine delivery system use with cigarette smoking progression or reduction among young adults. JAMA Netw Open. 2020;3(11):e2015893.
18.
SokolovskyAWHertelAWMicalizziLWhiteHRHayesKLJacksonKM. Preliminary impact of the COVID-19 pandemic on smoking and vaping in college students. Addict Behav. 2021;115:106783.
19.
KalkhoranSGlantzSA. E-cigarettes and smoking cessation in real-world and clinical settings: A systematic review and meta-analysis. Lancet Respir Med. 2016;4(2):116‐128.
20.
RehanHSMainiJHunginAPS. Vaping versus smoking: A quest for efficacy and safety of E-cigarette. Curr Drug Saf. 2018;13(2):92‐101.
21.
RomOPecorelliAValacchiGReznickAZ. Are E-cigarettes a safe and good alternative to cigarette smoking?Ann N Y Acad Sci. 2015;1340:65‐74.
22.
FarberHJConrado PachecoGMGaliatsatosPFolanPLamphereTPakhaleS. Harms of electronic cigarettes: What the health care provider needs to know. Ann Am Thorac Soc. 2020;18(4):567-572.
23.
KalkhoranSChangYRigottiNA. Electronic cigarette use and cigarette abstinence over 2 years among U.S. Smokers in the population assessment of tobacco and health study. Nicotine Tob Res. 2020;22(5):728‐733.
24.
Keller-HamiltonBLuBRobertsMEBermanMLRootEDFerketichAK. Electronic cigarette use and risk of cigarette and smokeless tobacco initiation among adolescent boys: A propensity score matched analysis. Addict Behav. 2021;114:106770.
25.
McAlindenKDEapenMSLuWSharmaPSohalSS. The rise of electronic nicotine delivery systems and the emergence of electronic-cigarette-driven disease. Am J Physiol Lung Cell Mol Physiol. 2020;319(4):L585‐L595.
26.
OsibogunOBursacZMcKeeMLiTMaziakW. Cessation outcomes in adult dual users of e-cigarettes and cigarettes: The population assessment of tobacco and health cohort study, USA, 2013–2016. Int J Public Health. 2020;65(6):923‐936.
27.
PattersonJGLaPoltDTMirandaAR, et al.Switching stories: user testimonials on juul.com continue to contradict JUUL's switch not equal cessation narrative. Tob Control. 2020;30(e1):e37–e40.
28.
FairchildALBayerRLeeJS. The E-cigarette debate: What counts as evidence?Am J Public Health. 2019;109(7):1000‐1006.
29.
FranksASSandoKMcBaneS. Do electronic cigarettes have a role in tobacco cessation?Pharmacotherapy. 2018;38(5):555‐568.
30.
RowellTRTarranR. Will chronic e-cigarette use cause lung disease?Am J Physiol Lung Cell Mol Physiol. 2015;309(12):L1398‐L1409.
31.
EllingtonSSalvatorePPKoJ, et al.Update: Product, substance-use, and demographic characteristics of hospitalized patients in a nationwide outbreak of E-cigarette, or vaping, product use-associated lung injury - United States, August 2019-January 2020. MMWR Morb Mortal Wkly Rep. 2020;69(2):44‐49.
32.
KingBAJonesCMBaldwinGTBrissPA. The EVALI and youth vaping epidemics - implications for public health. N Engl J Med. 2020;382(8):689-691.
33.
KligermanSRaptisCLarsenB, et al.Radiologic, pathologic, clinical, and physiologic findings of electronic cigarette or vaping product use-associated lung injury (EVALI): evolving knowledge and remaining questions. Radiology. 2020;294(3):491-505.
34.
KrishnasamyVPHallowellBDKoJY, et al.Update: Characteristics of a nationwide outbreak of E-cigarette, or vaping, product use-associated lung injury - United States, August 2019-January 2020. MMWR Morb Mortal Wkly Rep. 2020;69(3):90‐94.
35.
SalzmanGAAlqawasmaMAsadH. Vaping associated lung injury (EVALI): An explosive United States epidemic. Mo Med. 2019;116(6):492‐496.
36.
SaqiAMukhopadhyaySButtY, et al.E-cigarette or vaping product use-associated lung injury: What is the role of cytologic assessment?Cancer Cytopathol. 2020;128(6):371-380.
37.
AronsMMBarnesSRChengR, et al.Examining the temporality of vitamin E acetate in illicit THC-containing e-cigarette, or vaping, products from a public health and law enforcement response to EVALI - Utah, 2018–2020. Int J Drug Policy. 2020;88:103026.
RaoDRMapleKLDettoriA, et al.Clinical features of E-cigarette, or vaping, product use-associated lung injury in teenagers. Pediatrics. 2020;146(1):e20194104.
40.
ChatterjeeSCaporaleATaoJQ, et al.Acute e-cig inhalation impacts vascular health: A study in smoking naive subjects. Am J Physiol Heart Circ Physiol. 2021;320(1):H144‐H158.
41.
RohdeJANoarSMMendelJR, et al.E-Cigarette health harm awareness and discouragement: Implications for health communication. Nicotine Tob Res. 2020;22(7):1131‐1138.
42.
AshfordKWigginsAButlerKIckesMRayensMKHahnE. e-Cigarette use and perceived harm among women of childbearing age who reported tobacco use during the past year. Nurs Res. 2016;65(5):408‐414.
43.
GreeneRMPisanoMM. Developmental toxicity of e-cigarette aerosols. Birth Defects Res. 2019;111(17):1294‐1301.
44.
LiGChanYLNguyenLT, et al.Impact of maternal e-cigarette vapor exposure on renal health in the offspring. Ann N Y Acad Sci. 2019;1452(1):65‐77.
45.
LiGSaadSOliverBGChenH. Heat or burn? Impacts of intrauterine tobacco smoke and E-cigarette vapor exposure on the offspring's health outcome. Toxics. 2018;6(3):43.
46.
WagnerNJCamerotaMPropperC. Prevalence and perceptions of electronic cigarette use during pregnancy. Matern Child Health J. 2017;21(8):1655‐1661.
47.
WhittingtonJRSimmonsPMPhillipsAM, et al.The use of electronic cigarettes in pregnancy: A review of the literature. Obstet Gynecol Surv. 2018;73(9):544‐549.
48.
DobbsPDLuYManessS, et al.Gestational women's perceptions about the harms of cigarette and E-cigarette use during pregnancy. Matern Child Health J. 2020;25(8):1209-1220.
49.
KimSOanceaSC. Electronic cigarettes may not be a “safer alternative” of conventional cigarettes during pregnancy: Evidence from the nationally representative PRAMS data. BMC Pregnancy Childbirth. 2020;20(1):557.
50.
MoyseMHunterA. Newspaper media representation of electronic cigarette use during pregnancy. J Public Health (Oxf). 2020;43(1):e85-e91.
51.
RollinsLGSokolNAMcCallumM, et al.Electronic cigarette use during preconception and/or pregnancy: Prevalence, characteristics, and concurrent mental health conditions. J Womens Health (Larchmt). 2020;29(6):780‐788.
52.
RuszkiewiczJAZhangZGoncalvesFMTizabiYZelikoffJTAschnerM. Neurotoxicity of e-cigarettes. Food Chem Toxicol. 2020;138:111245.
CardenasVMFischbachLAChowdhuryP. The use of electronic nicotine delivery systems during pregnancy and the reproductive outcomes: A systematic review of the literature. Tob Induc Dis. 2019;17:52.
55.
HawkinsSSWylieBJHackerMR. Use of ENDS and cigarettes during pregnancy. Am J Prev Med. 2020;58(1):122‐128.
56.
LiuBXuGRongS, et al.National estimates of e-cigarette use among pregnant and nonpregnant women of reproductive age in the United States, 2014–2017. JAMA Pediatr. 2019;173(6):600‐602.
57.
MMWR C. Use of Electronic Vapor Products Before, During, and After Pregnancy Among Women with a Recent Live Birth — Oklahoma and Texas, 2015. 2019.
58.
BrelandAMcCubbinAAshfordK. Electronic nicotine delivery systems and pregnancy: Recent research on perceptions, cessation, and toxicant delivery. Birth Defects Res. 2019;111(17):1284‐1293.
59.
HolbrookBD. The effects of nicotine on human fetal development. Birth Defects Res C Embryo Today. 2016;108(2):181‐192.
60.
SuterMAMastrobattistaJSachsMAagaardK. Is there evidence for potential harm of electronic cigarette use in pregnancy?Birth Defects Res A Clin Mol Teratol. 2015;103(3):186‐195.
61.
DurhamELHowieRNCrayJJ. Gene/environment interactions in craniosynostosis: A brief review. Orthod Craniofac Res. 2017;20(Suppl 1):8‐11.
62.
CrayJJJr.DurhamELSmalleyMA, et al.The effects of testosterone on craniosynostotic calvarial cells: A test of the gene/environmental model of craniofacial anomalies. Orthod Craniofac Res. 2011;14(3):149‐155.
63.
CrayJJJr.KhaksarfardKWeinbergSMElsalantyMYuJC. Effects of thyroxine exposure on osteogenesis in mouse calvarial pre-osteoblasts. PLoS One. 2013;8(7):e69067.
64.
CrayJJJr.WeinbergSMParsonsTEHowieRNElsalantyMYuJC. Selective serotonin reuptake inhibitor exposure alters osteoblast gene expression and craniofacial development in mice. Birth Defects Res A Clin Mol Teratol. 2014;100(12):912‐923.
65.
DurhamEHowieRNParsonsT, et al.Thyroxine exposure effects on the cranial base. Calcif Tissue Int. 2017;101(3):300‐311.
66.
DurhamEHowieRNWarrenGLaRueACrayJ. Direct effects of nicotine exposure on Murine Calvaria and Calvarial cells. Sci Rep. 2019;9(1):3805.
67.
DurhamEJenSWangL, et al.Effects of citalopram on sutural and Calvarial cell processes. PLoS One. 2015;10(10):e0139719.
68.
DurhamELHowieRNBlackL, et al.Effects of thyroxine exposure on the twist 1 +/- phenotype: A test of gene-environment interaction modeling for craniosynostosis. Birth Defects Res A Clin Mol Teratol. 2016;106(10):803‐813.
69.
HowieRNDurhamELBlackL, et al.Effects of in utero thyroxine exposure on murine cranial suture growth. PloS one. 2016;11(12):e0167805.
70.
KesterkeMJJuddMAMooneyMP, et al.Maternal environment and craniofacial growth: Geometric morphometric analysis of mandibular shape changes with in utero thyroxine overexposure in mice. J Anat. 2018;233(1):46‐54.
71.
ParsonsTEWeinbergSMKhaksarfardK, et al.Craniofacial shape variation in Twist1+/- mutant mice. Anat Rec (Hoboken). 2014;297(5):826‐833.
72.
DurhamEHowieRNLarsonNLaRueACrayJ. Pharmacological exposures may precipitate craniosynostosis through targeted stem cell depletion. Stem Cell Res. 2019;40:101528.
73.
DurhamELBalogCHowieRN, et al.Effects of nicotine exposure on murine mandibular development. PLoS One. 2019;14(6):e0218376.
74.
CooperMHarrellMBPerryCL. A qualitative approach to understanding real-world electronic cigarette use: Implications for measurement and regulation. Prev Chronic Dis. 2016;13:E07.
75.
KimHDavisAHDohackJLClarkPI. E-Cigarettes use behavior and experience of adults: Qualitative research findings to inform E-cigarette use measure development. Nicotine Tob Res. 2017;19(2):190‐196.
76.
KosmiderLJacksonALeighNO'ConnorRGoniewiczML. Circadian puffing behavior and topography among E-cigarette users. Tob Regul Sci. 2018;4(5):41‐49.
77.
WongSWLinHCPiperMESiddiquiABuuA. Measuring characteristics of e-cigarette consumption among college students. J Am Coll Health. 2019;67(4):338‐347.
78.
AslanerDMAlghothaniOSaldanaTA, et al.E-cigarette vapor exposure in utero causes long-term pulmonary effects in offspring. Am J Physiol Lung Cell Mol Physiol. 2022;323(6):L676‐L682.
79.
NeczyporEWSaldanaTAMearsMJ, et al.e-Cigarette Aerosol reduces left ventricular function in adolescent mice. Circulation. 2022;145(11):868‐870.
80.
CrayJJr.KneibJVecchioneL, et al.Masticatory hypermuscularity is not related to reduced cranial volume in myostatin-knockout mice. Anat Rec (Hoboken). 2011;294(7):1170‐1177.
81.
KamdarMRGomezRAAschermanJA. Intracranial volumes in a large series of healthy children. Plast Reconstr Surg. 2009;124(6):2072‐2075.
82.
BuschangPHGandini JuniorLG. Mandibular skeletal growth and modelling between 10 and 15 years of age. Eur J Orthod. 2002;24(1):69‐79.
83.
EnlowDHHansMG. Essentials of facial growth.
84.
GonzalezPNOyhenartEEHallgrimssonB. Effects of environmental perturbations during postnatal development on the phenotypic integration of the skull. J Exp Zool B Mol Dev Evol. 2011;316(8):547‐561.
85.
MossML. The primacy of functional matrices in orofacial growth. Dent Pract Dent Rec. 1968;19(2):65‐73.
86.
MossML. A theoretical analysis of the functional matrix. Acta Biotheor. 1968;18(1):195‐202.
87.
MossMLBrombergBESongICEisenmanG. The passive role of nasal septal cartilage in mid-facial growth. Plast Reconstr Surg. 1968;41(6):536‐542.
88.
MossMLRankowRM. The role of the functional matrix in mandibular growth. Angle Orthod. 1968;38(2):95‐103.
89.
UgurluMOksayanRBayrakdarIS, et al.3D Evaluation of the relationship between different vertical growth patterns and cranial base angulations. J Neurol Surg B Skull Base. 2021;82(4):484‐490.
90.
ZollikoferCPBienvenuTPonce de LeonMS. Effects of cranial integration on hominid endocranial shape. J Anat. 2017;230(1):85‐105.
91.
CarstensMH. Development of the facial midline. J Craniofac Surg. 2002;13(1):129‐187; discussion 188–190.
92.
McBratney-OwenBIsekiSBamforthSDOlsenBRMorriss-KayGM. Development and tissue origins of the mammalian cranial base. Dev Biol. 2008;322(1):121‐132.
93.
PavlovMISautierJMOboeufMAsselinABerdalA. Chondrogenic differentiation during midfacial development in the mouse: In vivo and in vitro studies. Biol Cell. 2003;95(2):75‐86.
94.
SiegelMIMooneyMPKimesKRTodhunterJ. Analysis of the size variability of the human normal and cleft palate fetal nasal capsule by means of three-dimensional computer reconstruction of histologic preparations. Cleft Palate J. 1987;24(3):190‐199.
95.
SmithTDMcMahonMJMillenME, et al.Growth and development at the Sphenoethmoidal junction in perinatal primates. Anat Rec (Hoboken). 2017;300(12):2115‐2137.
96.
SmithTDRossieJBDochertyBA, et al.Fate of the nasal capsular cartilages in prenatal and perinatal tamarins (Saguinus geoffroyi) and extent of secondary pneumatization of maxillary and frontal sinuses. Anat Rec (Hoboken). 2008;291(11):1397‐1413.
97.
WeinbergSMMaherBSMarazitaML. Parental craniofacial morphology in cleft lip with or without cleft palate as determined by cephalometry: A meta-analysis. Orthod Craniofac Res. 2006;9(1):18‐30.
98.
RiceDP. Craniofacial anomalies: From development to molecular pathogenesis. Curr Mol Med. 2005;5(7):699‐722.
99.
TwiggSRWilkieAO. New insights into craniofacial malformations. Hum Mol Genet. 2015;24(R1):R50‐R59.
100.
BaroniTBellucciCLilliC, et al.Human cleft lip and palate fibroblasts and normal nicotine-treated fibroblasts show altered in vitro expressions of genes related to molecular signaling pathways and extracellular matrix metabolism. J Cell Physiol. 2010;222(3):748‐756.
101.
DickinsonAJGTurnerSDWahlSKennedyAEWyattBHHowtonDA. E-liquids and vanillin flavoring disrupts retinoic acid signaling and causes craniofacial defects in Xenopus embryos. Dev Biol. 2022;481:14‐29.
102.
KangPSvobodaKK. Nicotine inhibits palatal fusion and modulates nicotinic receptors and the PI-3 kinase pathway in medial edge epithelia. Orthod Craniofac Res. 2003;6(3):129‐142.
103.
OzturkFSheldonESharmaJCanturkKMOtuHHNawshadA. Nicotine exposure during pregnancy results in persistent midline epithelial seam with improper palatal fusion. Nicotine Tob Res. 2016;18(5):604‐612.
104.
SaadAYGartnerLPHiattJL. Teratogenic effects of nicotine on palate formation in mice. Biol Struct Morphog. 1990;3(1):31‐35.
105.
SellerMJBnaitKS. Effects of tobacco smoke inhalation on the developing mouse embryo and fetus. Reprod Toxicol. 1995;9(5):449‐459.
106.
LiQZhanYWangLLeischowSJZengDD. Analysis of symptoms and their potential associations with e-liquids’ components: A social media study. BMC Public Health. 2016;16:674.
