Harm reduction (HR) is a public health strategy developed initially in adults with substance-abuse problems when abstinence was not feasible. HR approaches have been effective in reducing morbidity and mortality in these adult populations, and in recent years has been applied to sexual health education to reduce both teen pregnancies and sexually transmitted disease, alcohol consumption and other risky behaviors. HR emphasizes the measurement of health, social, and economic outcomes, as opposed to the measurement of drug (or other substances) consumption.
HR efforts for fetuses exposed to maternal smoking would, ideally, be maternal tobacco smoking cessation and stopping all forms of nicotine. Some programs to reduce smoking during pregnancy have shown some success, but the goal of a tobacco free pregnancy is difficult to achieve [1]. While pregnancy appears to motivate 46% of pregnant women to quit smoking before or during pregnancy [2], cessation focused therapies including motivational interviewing, cognitive behavioral therapies, text messaging, and nicotine replacement therapies have been ineffective in persuading all pregnant women to quit [3,4,5]. An estimated 13 to 25% of American women continue to smoke tobacco during pregnancy. This is despite the known dose-dependent negative effects of smoking during pregnancy on infant birth weight and its contribution to preterm birth [6].
Use of alternative forms of nicotine delivery, such as electronic cigarettes and vaping, have increased substantially in recent years; however, minimal evidence demonstrates that these alternative nicotine delivery systems alter the detrimental health effects of nicotine exposure compared to traditional cigarettes. The promotion of electronic cigarettes as a method of HR has been falsely championed as a method to reduce cigarette smoking, when in fact, many pregnant women choose to combine both cigarette smoking and e-cigarette use rather than participate in cessation programs [7]. The U.S. Preventive Services Task Force has concluded that current evidence is insufficient to assess the balance of benefits and harms of nicotine replacement products or other pharmaceuticals for smoking cessation during pregnancy [8]. Further, conflicting evidence exists regarding whether nicotine replacement therapy increases abstinence rates of smoking during pregnancy, and it is does not appear to increase the odds of permanent smoking cessation during the postpartum period or during breastfeeding [9].
Several authors have reported reduced pulmonary function among preterm and term infants whose mothers smoked during pregnancy [10,11,12,13]. Recent evidence supports that much of the adverse effects of tobacco smoking during pregnancy on neonatal lung function is mediated by nicotine. Therefore, electronic cigarette use (or “vaping” nicotine) during pregnancy is likely also to have harmful effects on newborn lung function. For instance, McGrath–Morrow and colleagues demonstrated convincingly that exposure of neonatal mice to electronic cigarette vapor impaired lung growth and decreased body weight compared to vehicle (propylene glycol) [14].
Nicotine is a primary modulator of fetal lung development. Fetuses of mothers who smoke are exposed to nicotine in utero and multiple studies in animal models, including primates, clearly document that nicotine stunts fetal lung growth (alveolar and pulmonary vasculature development, airway growth, and reduces total lung weight). Various mechanisms have been proposed. Several years ago, McEvoy, et al. showed that a daily supplement of 500 mg vitamin C during pregnancy reduced abnormalities in neonatal pulmonary function and was associated with reduced relative risk of wheezing at 1 year of age by 56%[15]. Pharmacokinetic data suggest that 500 mg of vitamin C daily saturates vitamin C receptors and maximizes plasma concentrations [16]. McEvoy, et al. demonstrated that pregnant smokers randomized to 500 g of vitamin C had significantly increased levels of ascorbic acid compared to pregnant smokers randomized to placebo, and their vitamin C levels were to comparable to pregnant non-smokers in the trial.
Based on the McEvoy, et al. [15] data (and three other prospective birth cohorts that demonstrated longitudinal effects of fetal and infant smoking exposure through adolescence) in this issue of J Perinatology Yieh, et al. [17] develop an intriguing decision-analytic model to estimate the effect of maternal vitamin C administration on costs and outcomes specifically related to the burden of pregnancy-induced asthma in the United States. They considered primarily the extrapolated effect of additional maternal vitamin C supplementation to pregnant women who smoke during pregnancy on quality adjusted life years and asthma associated economic costs through adolescence for the US population. The economic impact was huge as was the improvement in quality adjusted life years. The author’s carefully describe limitations of their model and predictions, leading to new questions and where to next focus our efforts for HR.
In this issue, Yieh, et al. [17] estimate economic benefit of vitamin C supplementation, along with the usual prenatal vitamins, exceeds $30,000,000 over 18 years and increases quality adjusted life years by 19,200 for the >400,000 infants annually exposed to maternal smoking. This economic benefit whether measured in dollars saved or quality adjusted life years improved is “small change” considering the impact of asthma on childhood activities such as healthy exercise, sports participation, better school attendance, and improved self-esteem among these children. The reduction in cost burden to parents in terms of loss of work, trips to the emergency department, or for medications is also a major economic benefit. The analysis also predicted fewer deaths from asthma with this simple intervention, but childhood death secondary to asthma is a rare event.
How can the impact of this novel HR approach be proven to reduce asthma in childhood on a national or global scale? A large multicenter trial (with high power and with stringent p-values) could be undertaken to demonstrate vitamin C in addition to prenatal vitamins normalizes pulmonary function in newborns compared in a prenatal multi-vitamin alone. Such cohorts would require follow-up through at least 6 years to determine differences in asthma prevalence, needed medical services including hospitalization, and prescriptions to treat asthma. Alternatively, adopting the strategy that vitamin C supplementation for all pregnant women who smoke or use e-cigarettes could be compared with historical non-supplementation data.
All providers of maternity care should stress effective HR strategies by encouraging tobacco (and nicotine vaping) cessation when possible, recommending a healthy diet rich in ascorbic acid, and by prescribing supplemental vitamin C to mitigate the harm of nicotine to their fetuses, babies, and children.
Let us not delay.
References
Berard A, Zhao JP, Sheehy O. Success of smoking cessation interventions during pregnancy. Am J Obstet Gynecol. 2016;215:611.e1–611.eI. https://doi.org/10.1016/j.ajob.2016.06.059
Colman GJ, Joyce T. Trends in smoking before, during, and after pregnancy in ten states. Am J Prev Med. 2003;24:29–35.
Heminger C, Schindler-Ruwish JM, Abroms LC. Smoking cessation support pregnant women: role of mobile technology. Subst Abus Rehabil. 2016;7:15–26.
Nichter M, Nichter M, Adrian S, Goldade K, Tesler L, Muramoto M. Smoking and harm-reduction efforts among postpartum women. Qual Health Res. 2008;18:1184–94.
Adams KK, Beem A, Diener E, Merritt TA. Protecting the vulnerable: the importance of effective parental tobacco-dependence treatment during prenatal and newborn care. ped. Allergy Immuno Pulmonol. 2012;25:3–10.
Kataoka MC, Carvalheira APP, Ferrari AP, Malta MB, deBarros Leite Carvalhaes MA, deLima Parada CMG. Smoking during pregnancy and harm reduction in birth weight: a cross-sectional study. BMC Pregnancy Childbirth. 2018;18:67.
McCubbin A, Fallin-Bennett A, Barnett J, Ashford K. Perceptions and use of electronic cigarettes in pregnancy. Health Edu Res. 2017;32:22–32.
Siu AL, U.S. Preventive Services Task Force. Behavioral and pharmacotherapy interventions for tobacco smoking cessation in adult, including pregnant women: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2015;162:622–34.
Coleman T, Chamaberlain C, Davey MA, Coopr SE, Leonardi-Bee J. Pharmacological interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev. 2015; CD010078. https://doi.org/10.1002/14651858. Pub 2.
Milner AD, Marsch MJ, Ingram DM, Fox GF, Susiva C. Effectives of smoking in pregnancy on neonatal lung disease. Arch Dis Child Fetal Neonatal Ed. 1999;80:F8–14.
Lodrup Carlsen KC, Jaakkola JJ, Nafstad P, Carlsen KH. In utero exposure to cigarette smoking influences lung function at birth. Eur Respir J. 1997;10:1774–9.
Brown RW, Hanrahan JP, Castile RG, Tager IB. Effect of maternal smoking during pregnancy on passive respiratory mechanics in early infancy. Pediatr Pulmonol. 1995;19:23–8.
Håland G, Lødrup K, Sandvik L, Devulapalli CS, Munthe-Kaas MD, pettersen M, Hai-Håkon C. Reduced lung function at birth and the risk of asthma at 10 years of age. N Engl J Med. 2006;355:1682–9.
McGrath-Morrow SA, Havashi M, Aberrera A, Lopez A, Malinina A, et al. The effects of electronic cigarette emissions on systemic cotinine levels, weight and postnatal lung growth in neonatal mice. PLoS One. 2015;10:e0118344 https://doi.org/10.1371/journal.pone.0118344.
McEvoy C, Schilling D, Clay N, Jackson K, Go MD, Spitale P, et al. Vitamin C supplementation for pregnant smoking women and pulmonary function in their newborn infants. JAMA. 2014;311:2074–82.
Levine M, Wang Y, Padayatty SJ, Morrow J. A new recommended dietary allowance of Vitamin C for healthy young women. Proc Natl Acad Sci USA. 2001;98:9842–6.
Yieh L, McEvoy CT, Hoffman SW, Caughey AB, MacDonald DK, Dukhovny D. Cost-effectiveness of vitamin C supplementation for pregnant smokers to improve offspring lung function at birth and reduce childhood wheeze/asthma. J Perinatol. 2018;7 https://doi.org/10.1038/s41372-018-0135-6
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Merritt, T.A. Improving fetal lung development with vitamin C and reducing asthma in children. J Perinatol 38, 775–777 (2018). https://doi.org/10.1038/s41372-018-0148-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41372-018-0148-1