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ORIGINAL RESEARCH |
From the Departments of Medicine, Obstetrics and Gynecology, and Psychiatry, and the Lowell P. Weicker, Jr. General Clinical Research Center, University of Connecticut School of Medicine, Farmington, Connecticut.
Address reprint requests to: Cheryl Oncken, MD, MPH, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-3940; E-mail: oncken{at}nso2.uchc.edu.
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ABSTRACT |
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METHODS: Fifteen chronic smokers who were between 28 and 36 weeks’ gestation were evaluated during an 8-hour smoking session. Baseline FHR and reactivity were evaluated before an initial cigarette and 4 hours later (after the fourth cigarette), when the effects of smoking on FHR were expected to be maximal. Plasma nicotine was measured at baseline and repeated at times of fetal monitoring.
RESULTS: Subjects smoked a mean ± standard deviation of 22 ± 6 cigarettes per day. They abstained from smoking for 9.2 ± 3.2 hours before evaluation. The initial baseline FHR was 134 ± 9 beats per minute versus 135 ± 11 beats per minute after the fourth cigarette (P =.17). Plasma nicotine increased from 2.6 ± 5.6 ng/mL to 24 ± 9.9 ng/mL after the fourth cigarette (P < .001). The initial nonstress test was reactive in 12 of 15 (80%) of the fetuses. After the fourth cigarette, only four of 15 (27%) of the nonstress tests were reactive. A majority of tracings (eight of 15) were initially reactive before smoking and became nonreactive after smoking. Some tracings remained nonreactive (three of 15), and some tracings remained reactive (four of 15) at both assessments. None of the tracings that were initially nonreactive became reactive. The change in reactivity was significant (P = 013).
CONCLUSION: Acute, repeated smoking decreases FHR reactivity.
Cigarette smoking is known to have many adverse effects on the outcome of a pregnancy. Maternal smoking increases the risk of spontaneous abortion,1–3 placental abruption, preterm premature rupture of membranes, preterm delivery, and fetal growth restriction.4–7 All of these problems can contribute to the increased perinatal morbidity and mortality associated with cigarette smoking during pregnancy. Beyond these acute effects, there may also be long-term adverse effects on the intellectual development and health of the child.8–11
Although there are approximately 3000 chemicals in tobacco, carbon monoxide and nicotine are present in the greatest concentrations. The animal literature suggests that carbon monoxide and nicotine may contribute to poor pregnancy outcomes.12 Both of these chemicals are hypothesized to lower fetal oxygenation and uterine perfusion,13 which would be expected to have a negative impact on fetal physiology.14 Fetal heart rate (FHR) measures (eg, variability, baseline, and reactivity) are dependent on uterine perfusion and oxygenation. Consequently, they may be affected by maternal smoking. Smoking could also affect FHR variability because of nicotine’s effect on fetal sympathetic activation, or may be a direct drug effect of nicotine. Thus, a decrease in FHR reactivity may not necessarily reflect fetal hypoxia.
Although many studies suggest that smoking may decrease FHR variability or reactivity, the literature is not consistent. Although in some studies smoking decreases FHR variability,13,15 in other studies, there are contradictory effects of smoking on FHR baseline13,15,16 or heart rate reactivity.16–18 These variable effects may be due to differences in study design. In previous reports, not all study subjects smoked chronically during pregnancy, the amount of time patients abstained from smoking before fetal evaluation was brief or not standardized, and patients did not smoke during the study session or they smoked only one cigarette.
The aim of this study was to examine the effects of acute, repeated smoking on FHR in mothers who smoked chronically during pregnancy. We hypothesized that continued smoking would decrease FHR reactivity. This report is a preliminary analysis of observations of the effects of smoking on FHR characteristics.
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MATERIALS AND METHODS |
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This protocol was approved by the Institutional Review Board of the University of Connecticut Health Center, and written, informed consent was obtained from all participants. Subjects in the study were at least age 16 (parental consent was obtained if under 18 years old), smoked at least ten cigarettes per day, were not currently using smokeless tobacco products or bupropion, were between 28 and 36 weeks’ gestation, had no allergy or hypersensitivity to adhesive tape, and were not currently using illicit drugs or alcohol. On history and physical examination, patients were excluded if they had hypertension, cardiac disease, uncontrolled diabetes, peptic ulcer disease, sinusitis, or unstable psychiatric illness. To ensure active smoking, patients underwent end-expired carbon monoxide assessment using a Vitalograph carbon monoxide monitor (Vitalograph Inc., Lenexa, KS). Carbon monoxide concentrations of more than 8 parts per million were considered consistent with smoking. Patients also had an obstetric ultrasound to ensure that there was a single fetus without evidence of fetal growth restriction (ie, estimated fetal weight less than 5th percentile for gestation) or a major fetal anomaly.
Patients who passed the screening evaluation were entered into the baseline smoking protocol. Patients were instructed to limit their smoking to ten to 15 cigarettes per day for the 5 days before the study session and to abstain from smoking the night before the study session. They kept a smoking diary to record their daily cigarette use and the time of their last cigarette before the monitoring session. Patients arrived for the 8-hour monitoring session by 8:00 AM. They were given a breakfast meal, which consisted of juice, and either a muffin, a bagel, or cereal. Subjects were not allowed to eat at times other than as designated by the study protocol.
An indwelling venous catheter was placed for baseline and serial assessment of blood samples (plasma nicotine and cotinine). Blood samples were repeated to correspond with peak and trough levels of smoking. Peak concentrations were obtained 10 minutes after the onset of smoking a cigarette, and trough levels were obtained immediately before smoking. After blood samples were obtained, they were sent to the General Clinical Research Center core laboratory for processing and storage. Plasma samples for nicotine and cotinine were stored at -70C for later batch analysis by gas chromatography on a Hewlett-Packard model 5890 (Hewlett-Packard, Andover, MA) using a nitrogen-phosphorus detector.19
Other measurements obtained during the monitoring session included an 8-hour urine collection for cat-echolamines and ultrasound measures for fetal breathing movements. Fetal breathing movements were assessed by real-time ultrasound, using a General Electric RT 3600 with a 3.5-MHz linear transducer (Rancho Cordova, CA). Ultrasound assessment of fetal breathing was performed at different times than FHR testing and will be the subject of another report.
After breakfast, a baseline nonstress test (NST) (up to 30 minutes) was conducted. If the tracing was reactive before 30 minutes, the subject was taken off the monitor. Otherwise, monitoring was continued for a total time of 30 minutes. During the fetal monitoring, patients were recumbent in a semifowler position with lateral tilt. The NST was performed using an Advanced Medical Systems model IM77 FHR monitor (Spacelabs Medical, Hamden, CT). The NST was considered reactive if there were two accelerations of at least 15 beats per minute above baseline for 15 seconds, in a 10-minute window. Patients were then allowed to smoke their usual brand of cigarette, one per hour for the 8-hour session. The smoking and monitoring were done in a negative pressure room to allow adequate ventilation.
Patients were provided with juice and crackers approximately 1 hour before the second NST. The NST was repeated approximately 5–10 minutes after the completion of the fourth cigarette when the effects of smoking on FHR were expected to be maximal.
Statistical analysis was analyzed using the McNemar test and paired t test. A P value of < 0.05 was considered statistically significant. It is noteworthy that two patients were on methadone treatment. Results were done with and without these two individuals, and because the results were the same, data from these subjects are included in the results presented here.
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RESULTS |
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Plasma nicotine concentrations and FHR characteristics before (trough level) and after (peak level) smoking the first cigarette of the day, and after the fourth cigarette of the day (peak level) are provided in Table 1
. Compared with the baseline value, there was a significant increase in the plasma nicotine concentration after the first cigarette, with a further increase after the fourth cigarette. Although most individuals had nicotine concentrations below the limit of assay detection (ie, 5 ng/mL), three individuals had nicotine levels greater than 5 ng/mL. Two of these individuals reported that their last cigarette was approximately 12 hours before the study session, and they also had an initial reactive NST. It is noteworthy that nicotine concentrations can be detected in some individuals even after overnight cigarette abstinence.20 The one individual with a nonreactive NST and plasma nicotine level of 18 ng/mL reported smoking 1/2 hour before the initial NST testing.
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). After an overnight abstinence from cigarette smoking, the initial NST was reactive in 12 of 15 (80%) of the fetuses. After the fourth cigarette, only four of 15 (27%) of the NSTs were reactive (Table 1). The majority of tracings that were initially reactive before smoking became nonreactive after smoking (eight of 15), some tracings were nonreactive throughout (three of 15), and some tracings remained reactive at both assessments (four of 15). None of the tracings that were initially nonreactive later became reactive (McNemar test: 
2 = 6.13, 1 degree of freedom, P =.013). All of the fetuses demonstrated fetal breathing movement consistent with clinical well-being during and at the end of the monitoring session. |
DISCUSSION |
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Some of our observations agree with previous reports in the literature. Differences in these findings from those previously reported may be due to the more controlled nature of our protocol. In the present study, abstinence from smoking was of sufficient duration that most of the women started the session with an undetectable plasma nicotine concentration. Thus, there would have been a negligible effect of smoking on the fetal heart at the time when the FHR baseline was initially evaluated. Indeed, most of our subjects had a reactive NST in the morning after overnight cigarette abstinence, which is similar to the results observed in other studies in pregnant smokers who had a smoke-free period before FHR testing.16,21 In contrast, Phelan18 did not record the time of the last cigarette before smoking, and Barrett et al17 had mothers abstain for only 1 hour before the NST. Phelan18 did not have mothers smoke before the NST was performed, and Barrett et al,17 Lehtovirta et al,13 and Graca et al16 had mothers smoke only one cigarette. In the study by Lehtovirta et al,13 88% of the patients had stopped smoking during the pregnancy. In contrast, patients in the current study were chronic smokers who, on average, consumed more than 20 cigarettes per day (ie, which identifies them as heavy smokers).4 Furthermore, even though the majority of our patients reported a decrease in smoking during pregnancy, they continued to be heavy smokers. On the day of fetal testing, they smoked repeatedly during the monitoring session. This study design is more representative of a real-life situation because with continued smoking, nicotine concentrations usually rise throughout the day until a steady state is reached during the early afternoon.22 An increase in the concentration of nicotine, or of another component of tobacco smoke, could account for the negative effect of smoking on the FHR reactivity that was observed. Examination of the nicotine concentrations in Table 1 reveals an increase after the first cigarette of the day and further increases after the fourth cigarette of the day.
The study was limited by the fact that the fixed-dose design does not allow determination of how many cigarettes are needed to produce this effect on the NST. Systemic absorption of nicotine is approximately 1 mg per cigarette, and 11 mg per cigarette for carbon monoxide.23 Based on the observations from Barrett et al,17 one cigarette may not be sufficient to change the reactivity. In that study, once the fetus was monitored to obtain a reactive NST, smoking one cigarette did not affect the reactivity. In contrast, Graca et al found that smoking a single cigarette does decrease reactivity.16 Also, we are unable to determine how long the effect of smoking lasts because monitoring was not continuous. The effect is probably less than 1 hour because in our previous study, where NSTs were performed at baseline and again after 4 hours of continued smoking, only one of 15 tracings lost reactivity.24 However, in that study, NSTs were not standardized in relation to maternal smoking. In the present study, we obtained the NST immediately after smoking to correspond with peak nicotine levels. The idea that the effect of smoking on FHR reactivity is temporary is supported by Phelan’s study,18 in which smokers who had a nonreactive test one week may have had a reactive test the next week. Although the number of patients in this study is small, the sample size is larger than those in previous reports designed primarily to determine the effect of smoking on FHR characteristics.13,15 We are continuing to enroll subjects in this protocol, which will enable us to compare the effect of smoking with that of nicotine administered via different delivery systems on FHR characteristics.
That the majority of reactive NSTs can become nonreactive after repetitive smoking has important implications for antepartum fetal evaluation. Based on the findings of this study, it would seem prudent to inquire of all patients who are undergoing FHR testing whether they are active cigarette smokers and how recently they have smoked a cigarette. In the face of recent smoking and a nonreactive NST, further fetal evaluation might initially consist of waiting a period of time before repeating the NST. If the test remains nonreactive, additional efforts should be made to distinguish a possible temporary effect of cigarette smoking from some underlying pathologic effect on fetal oxygenation.
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Footnotes |
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Received August 29, 2001. Received in revised form December 12, 2001. Accepted January 17, 2002.
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REFERENCES |
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This article has been cited by other articles:
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  P. S. Zeskind and J. L. Gingras Maternal Cigarette-Smoking During Pregnancy Disrupts Rhythms in Fetal Heart Rate J. Pediatr. Psychol., January 1, 2006; 31(1): 5 - 14. [Abstract] [Full Text] [PDF]
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 J. Bernardes, C. Oncken, H. Kranzler, and W. Campbell The Effect of Cigarette Smoking on Fetal Heart Rate Characteristics Obstet. Gynecol., October 1, 2002; 100(4): 828 - 829. [Full Text] [PDF]
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