Despite significant population level declines, smoking during pregnancy remains a major public health issue in the United States (US). Approximately 360,000-500,000 smoke-exposed infants are born yearly, and prenatal smoking remains a leading modifiable cause of poor birth outcomes (e.g. birth < 37 gestational weeks, low birth weight, perinatal mortality). Women who smoke during pregnancy are more likely to be younger and from disadvantaged socioeconomic and racial and ethnic groups, with some US geographic regions reporting increased prenatal smoking rates since 2000. Such disparities in maternal prenatal smoking suggests some pregnant women face unique barriers to cessation. This paper reviews the current state and future direction of smoking cessation in pregnancy in the US. We briefly discuss the etiology of smoking addiction among women, the pathophysiology and effects of tobacco smoke exposure on pregnant women and their offspring, and the emerging issue of electronic nicotine delivery systems. Current population-based and individual smoking cessation interventions are reviewed in the context of pregnancy and barriers to cessation among US women. Finally, we consider interventions that are on the horizon and areas in need of further investigation.
Rationale: We reported a randomized trial demonstrating daily supplemental vitamin C to pregnant smokers significantly improved newborn pulmonary function tests. The current study tests these results in a new cohort using infant pulmonary function tests.Objectives: To determine if infants of pregnant smokers randomized to daily supplemental vitamin C would have improved forced expiratory flows (FEFs) at 3 months of age compared with those randomized to placebo, and to investigate the association of the a5 nicotinic acetylcholine receptor.Methods: A randomized, double-blind, placebo-controlled trial was conducted at three centers. Two hundred fifty-one pregnant smokers were randomized at 13-23 weeks of gestation: 125 randomized to vitamin C (500 mg/d) and 126 to placebo.Measurements and Main Results: The primary outcome was FEF 75 at 3 months of age performed with the raised volume rapid thoracic compression technique (Jaeger/Viasys). FEF 50 and FEF 25-75 obtained from the same expiratory curves were prespecified secondary outcomes. The infants of pregnant smokers randomized to vitamin C (n = 113) had the following FEFs at 3 months of age compared with those randomized to placebo (n = 109) as measured by FEF 75 (200.7 vs. 188.7 ml/s; adjusted 95% confidence interval [CI] for difference, 23.33 to 35.64; P = 0.10), FEF 50 (436.7 vs. 408.5 ml/s; adjusted 95% CI for difference, 6.10-61.30; P = 0.02), and FEF 25-75 (387.4 vs. 365.8 ml/s; adjusted 95% CI for difference, 0.92-55.34; P = 0.04). Infant FEFs seemed to be negatively associated with the maternal risk alleles for the a5 nicotinic acetylcholine receptor (rs16969968).Conclusions: Although the primary outcome of FEF 75 was not improved after vitamin C supplementation to pregnant smokers, the predetermined secondary outcomes FEF 50 and FEF 25-75 were significantly improved. These results extend our previous findings and demonstrate improved airway function (FEF 50 and FEF 25-75 ) at 3 months of age in infants after vitamin C supplementation to pregnant smokers. Clinical trial registered with www.clinicaltrials.gov (NCT 01723696).
Despite strong anti-smoking efforts, at least 12% of American women cannot quit smoking when pregnant resulting in more than 450,000 smoke-exposed infants born yearly. Smoking during pregnancy is the largest preventable cause of childhood respiratory illness including wheezing and asthma. Recent studies have shown a protective effect of vitamin C supplementation on the lung function of offspring exposed to in utero smoke in a non-human primate model and an initial human trial. Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function (VCSIP) is a randomized, double-blind, placebo-controlled trial to evaluate pulmonary function at 3 months of age in infants delivered to pregnant smokers randomized to 500 mg/day of vitamin C versus placebo during pregnancy. Secondary aims evaluate the incidence of wheezing through 12 months and pulmonary function testing at 12 months of age. Women are randomized between 13–23 weeks gestation from clinical sites in Portland, Oregon at Oregon Health & Science University and PeaceHealth Southwest Medical Center and in Indianapolis, Indiana at Indiana University and Wishard Hospital. Vitamin C supplementation occurs from randomization to delivery. Monthly contact with participants and monitoring of medical records is performed to document medication adherence, changes in smoking and medical history, and adverse events. Pulmonary function testing of offspring occurs at 3 and 12 months of age and incidence of wheezing and respiratory illness through 12 months is captured via at least quarterly questionnaires. Ancillary studies are investigating the impact of vitamin C on placental blood flow and DNA methylation.
Maternal obesity prior to and during pregnancy has been associated with an increased incidence of childhood asthma. As diets rich in saturated fat are linked to obesity and inflammation, we created a murine model to investigate the effect of maternal high‐fat diet (HFD) on adult offspring airway hyperreactivity (AHR), a cardinal feature of asthma. Balb/cByJ dams were fed a HFD (60% fat Calories) or normal‐fat diet (NFD) (10% fat Calories) from 8 weeks prior to first breeding through their pregnancies. Pups were weaned to either a HFD or NFD (at 4 weeks of age). AHR was measured in the 10‐week‐old offspring following inhaled methacholine challenge by end‐inflation technique. Bronchial alveolar lavage fluid (BALF) was analyzed for cell count, total protein, and IL‐6. Offspring of HFD dams weaned to NFD had increased AHR compared to offspring of NFD dams weaned to NFD. Offspring of HFD dams that remained on HFDs had increased AHR compared to offspring of NFD dams weaned to HFDs. Offspring of HFD dams had higher BALF cell counts, higher neutrophil percentage, greater total protein, and IL‐6 in the BALF. These results demonstrate that a maternal diet high in saturated fat through pregnancy and lactation plays a key role in programming adult offspring AHR.
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