Exposure to Environmental and Mainstream Tobacco Smoke and Risk ...

American Journal of Epidemiology Copyright C 1999 by The Johns Hopkins University School of Hygiene and Public Hearth All rights reserved

Vol. 149, No. 3

Pnnted in U.SA.

Exposure to Environmental and Mainstream Tobacco Smoke and Risk of Spontaneous Abortion

Gayle C. Windham,1 Julie Von Behren,1 Kirsten Waller,1'2 and Laura Fenster1 The authors examined the risk of spontaneous abortion from environmental tobacco smoke (ETS) exposure in a prospective study of over 5,000 women conducted in California during 1990-1991. Among nonsmokers, there was little association by hours of ETS exposure at home or work (adjusted odds ratio (OR) for any exposure = 1.01, 95% confidence interval (Cl) 0.80-1.27), or by paternal smoking. However, the risks associated with ETS exposure were increased among nonsmokers who had moderate alcohol or heavy caffeine consumption. A moderate association with maternal smoking was observed (adjusted OR for >5 cigarettes per day = 1.3, 95% Cl 0.91-1.9). Am J Epidemiol 1999; 149:243-7. abortion, spontaneous; pregnancy; tobacco smoke pollution

MATERIALS AND METHODS

Details of data collection have been published elsewhere (7, 8) and are summarized briefly here. Pregnant women were recruited during 1990-1991 from a large Received for publication November 18, 1997, and accepted for publication June 15, 1998. Abbreviations: Cl, confidence interval; ETS, environmental tobacco smoke; OR, odds ratio; SAB, spontaneous abortion. 1 Environmental Health Investigations Branch, Department of Health Services, Oakland, CA. 2 Currentty with Public Health Institute, Berkeley, CA. Reprint requests to Dr. Gayle Windham, Department of Health Services, 1515 Clay Street, Suite 1700, Oakland, CA 94612.

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prepaid health plan in California when they called to make their first prenatal appointment. To be eligible for the study, pregnant women had to be at least 18 years old, 12 weeks gestation or less (mean = 8 weeks), and Spanish- or English-speaking. Telephone interviews were completed within a few weeks of initial contact for 5,342 women; reasons for noncompletion included 18 percent refusals, about 10 percent ineligible, and 3 percent lost to follow-up. Pregnancy outcomes were ascertained primarily by computerized hospital admission records and abstraction of medical records. Less than one percent of outcomes could not be determined. These pregnancies were excluded as were therapeutic abortions and ectopic or molar pregnancies (n = 198). Pregnancies that ended by 20 completed weeks of gestation or earlier were defined as spontaneous abortions (n = 499). The remaining pregnancies resulted in 4,613 livebirths and 32 stillbirths. Most of the consumption questions on the interview (e.g., alcohol, caffeinated beverages, and cigarettes smoked) were asked for two time periods: the week before interview (considered "during" pregnancy) and the week at last menstrual period. The smoking status of the spouse was also ascertained during pregnancy, but the amount he smoked was ascertained only for the 3 months before pregnancy. Exposure to ETS was ascertained as the average number of hours per day the respondent was near other people smoking at home and at work since the last menstrual period. Hours at the two locations were summed to create a total daily ETS exposure. ETS exposure was examined only among women who reported not smoking at both time periods (n = 4,209).

Maternal smoking during pregnancy is considered a hazard to the fetus (1,2). Studies of spontaneous abortion have generally found an association: reviews of the literature suggest increased risks on the order of 25-50 percent, with some studies showing greater effects with heavier smoking (3, 4). Because of these risks, exposure to environmental tobacco smoke (ETS) is also of concern. To our knowledge, only two studies have examined spontaneous abortion in relation to ETS exposure—one a case-control study that we conducted in California (5) and the other a prospective study carried out in Sweden (6). Both studies had similar findings of about a 50 percent increased risk, but had various limitations including only limited exposure ascertainment in the case-control study. Therefore, we have examined this issue further in a prospective study of spontaneous abortion which ascertained usual daily hours of ETS exposure at home and work. In addition, we present data on maternal and paternal smoking.

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Windham et al.

The hours of ETS exposure were categorized and crude risk ratios and 95 percent confidence intervals for spontaneous abortion were calculated relative to nonexposed. Any exposure versus none was entered in logistic regression models because there was little increase in risk (univariately) by greater hours exposed. Odds ratios were adjusted for maternal age, prior history of spontaneous abortion, alcohol and caffeine consumption during pregnancy, and gestational age at interview. Potential effect modifiers of a priori interest from previous smoking studies were alcohol and caffeine consumption, which were examined for departure from additivity of effects (9, 10). Effects of active smoking were examined using similar logistic regression models. RESULTS

variable Maternal age (years) 5/day) appeared greater for losses which occurred after 10 weeks (adjusted odds ratio (OR) = 1.6, 95 percent confidence interval (CI) 1.0-2.4) than for earlier abortions (adjusted OR = 0.9, 95 percent CI 0.6-1.7). There was slight effect modification of the active smoking association by caffeine consumption of >150 mg/day, but not when categorized as >300 mg/day. There was no effect modification by alcohol consumption during pregnancy, nor by spouse smoking habits. DISCUSSION

This prospective study found little evidence for an association of spontaneous abortion with ETS expoAm J Epidemiol

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The proportion of spontaneous abortions was 9.7/100 (9.6/100 among nonsmokers). The median gestational age at loss was 11 weeks, with 72 percent of spontaneous abortions occurring in the first trimester. Risk factors for spontaneous abortion in these data (table 1) were similar to those generally found in the literature (11). Among nonsmoking women, 13.5 percent reported ETS exposure at home and 23 percent of working women reported ETS exposure at work (figure 1), with about 28 percent exposed overall. Although more women reported exposure at work than home, much of the exposure tended to be of short duration. The proportion of spontaneous abortions did not increase consistently with increasing ETS exposure (table 1). When examined by source of exposure, miscarriage risk was somewhat elevated at >6 hours per week of home exposure compared with none (11.4/100 vs. 9.4/100), but greater hours of work exposure were not associated with greater risk of spontaneous abortion. The adjusted odds ratios for any ETS exposure by source were all close to null (table 2). Some effect modification by alcohol and caffeine consumption was found (table 3). There was no difference in the ETS association for earlier versus later losses. Among nonsmokers, 15.5 percent of women reported that the father of the pregnancy smoked. The risk of spontaneous abortion was not increased with his smoking status during pregnancy, nor with amount smoked by the father before pregnancy (table 4). Combining women who reported either ETS exposure at home or spouse smoking or both did not identify any increased risks for spontaneous abortion. In comparison, women who smoked >5 cigarettes per day during pregnancy were 40 percent more likely to have a spontaneous abortion than nonsmokers (table 5), but there was little dose-response trend for greater

TABLE 1. Proportion of spontaneous abortions (SABs) by selected demographic factors and environmental tobacco smoke (ETS) exposure during pregnancy, California, 1990-1991

Tobacco Smoke Exposure and Risk of Spontaneous Abortion

245

%

Exposed

Work ETS Exposure

Home

Total

TABLE 2. Adjusted* odds ratios (OR) for spontaneous abortion (SAB) and environmental tobacco smoke (ETS) exposure during pregnancy, among nonsmokers, California, 1990-1991 Variable

Any ETS at home Any ETS at work Any ETS, either place

No.

SAB (%)

Adjusted OR

95%Clt

571 743 1,178

10.9 9.0 9.6

1.15 0.88 1.01

0.86-1.55 0.66-1.17 0.80-1.27

* Adjusted for maternal age, prior spontaneous abortion, alcohol and caffeine consumption, and gestational age at interview, and compared with nonexposed for each source. t Cl, confidence interval.

sure, except among women who also consumed alcohol or caffeine in moderate to high amounts. The increase in risk seen with active maternal smoking is consistent with previous reports (3,4). Women who consume alcohol or caffeine may be more susceptible to further risks from ETS than other women. However, effect modification of alcohol and caffeine on the relation with smoking was not seen clearly in this study nor in previous studies (5, 11-13), so these findings are tenuous. We are aware of only two previous studies of spontaneous abortion with data on ETS exposure other than spousal smoking, which were limited to nonsmoking mothers and adjusted for confounders (5, 6). Both reported a moderate association of spontaneous abortion with ETS exposure, which we would have been able to detect with greater than 80 percent power. In Am J Epidemiol

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the Swedish study (6), the association was observed only with workplace exposure (adjusted relative risk = 1.5, 95 percent CI 1.0-2.4), which was defined as spending most of the time at work around smokers. The California study (5) did not ask about sources of exposure separately, but rather whether subjects were exposed to ETS for >1 hours per day at home or work (adjusted OR = 1.6, 95 percent CI 1.2-2.1). These findings are of similar or greater magnitude to the associations found between spontaneous abortion and active smoking in the same data sets. ETS contains many of the same chemical constituents as those in mainstream smoke, but the physiochemical nature of sidestream smoke compared with mainstream smoke leads to differences in the ratio of constituents, which may be higher in sidestream smoke (14). Sidestream smoke undergoes dilution and further chemical transformation to form ETS. Because cotinine levels measured in nonsmokers who are exposed to ETS are generally one to two orders of magnitude lower than in smokers (15), the effect of ETS exposure might be expected to be much lower than that of active smoking. However, this presupposes a linear relation and that cotinine (a metabolite of nicotine) is the primary toxicant of interest (14). The current study is based on more detailed assessment of ETS exposure than the previous California study (5), but may be subject to some misclassification (and nullification of risks) because exposures outside the home or workplace were not ascertained, nor


FIGURE 1. Proportion of nonsmokers who reported exposure to environmental tobacco smoke (ETS) at home, work, and combined, by hours exposed, in a prospective study of pregnancy outcome, California, 1990-1991.

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Windham et al. TABLE 3. Additive models for effect modification of caffeine and alcohol on association of environmental tobacco smoke (ETS) and spontaneous abortion (SAB), in nonsmokere, California, 1990-1991 Caffeine consumption ETS

Caffeine (mg/day)

None Any None Any

£300

£300 >300 >300

No.

2,955 1,138 61

40

SABs

9.6 8.9 9.8 27.5

Alcohol consumption

Adjusted' ' 95% Clf ORt

§ 0.93 0.84 3.4

0.73-1.2 0.35-2.0 1.7-7.0

RERIf = 3.4-0 .93-0.84 + 1 = 2.6 (0.2-5.0)

Alcohol (drinks/wtc)

NO.

3,002 1,168 14 10

S3 S3

>3 >3

SABs (%)

9.6 9.3 14.3 30.0

Adjusted OR

§ 0.98 1.0 2.9

95% Cl

0.78-1.2 0.22^1.8 0.72-11.6

RERI = 2.9-0.98-1.0 + 1 = 1.9 (0.2-3.6)

* Adjusted for maternal age and alcohol use. t OR, odds ratio; Cl, confidence Interval; RERI, relative excess risk due to interaction and 95% Cl of this risk difference (see references 9 and 10). X Adjusted for maternal age and caffeine use. § Reference group

TABLE 4. Proportion of spontaneous abortions (SABs) by paternal smoking* among maternal nonsmokers, California, 1990-1991 No.

SABs(%)

0 1-10 11-20 >20

3,550 405 186 55

9.6

Adjusted* 0 R +

95% CI*

Maternal smoking (cigarettes/day) 0

9.4

§ 0.98

0.73-1.3

9.1 10.9

1-4 5-9

0.97

0.41-2.3

£10

* Amount father smoked during 3 months before last menstrual period. t Adjusted by logistic regression for maternal age, prior fetal loss, alcohol and caffeine consumption, and gestational age at interview. X OR, odds ratio; Cl, confidence interval. § Reference group.

were details about the intensity of exposure. The proportion of nonsmokers who reported ETS exposure is lower than in some studies, but is similar to our study conducted 4 years earlier and to other studies in California of nonpregnant women (5, 17). California has lower smoking rates than other states and more severe smoking restrictions (17, 18), so that exposure to ETS may not only be less frequent but also of a lower magnitude or intensity. To date, the literature on the possible association of ETS exposure and fetal loss is somewhat limited. Additional studies should include highly exposed women to provide power for detecting a possible association and more detailed exposure assessment.

REFERENCES 1. US Department of Health and Human Services. The health consequences of smoking for women: a report of the Surgeon General. Atlanta, GA: USDHHS, Public Health Service, Office of the Assistant Secretary for Health, Office of Smoking and Health, 1980.

No

SABs (%)

Adjusted OR

4,607 209 119 208

9.4 9.6 13.5 13.5

+ 0.91

} 13

95% Clt

0.56-1.5 0.91-1.9

* Adjusted for maternal age, prior fetal loss, alcohol and caffeine consumption during pregnancy, and gestational age at interview, t Cl, confidence interval. X Reference group.

2. Stillman RJ, Rosenberg MJ, Sachs BP. Smoking and reproduction. Fertil Steril 1986;46:545-66. 3. Windham GC. Effects of tobacco smoke on risk of spontaneous abortion. In: Current issues in smoking and reproductive health. ARHP Clinical Proceedings 1996:13-15. 4. DiFranza JR, Lew RA. Effect of maternal cigarette smoking on pregnancy complications and sudden infant death syndrome. J Fam Pract 1995;40:385-94. 5. Windham GC, Swan SH, Fenster L. Parental cigarette smoking and the risk of spontaneous abortion. Am J Epidemiol 1992; 135:1394-1403. 6. Ahlborg G Jr, Bodin L. Tobacco smoke exposure and pregnancy outcome among working women. A prospective study at prenatal care centers in Orebro County, Sweden. Am J Epidemiol 1991;133:338-47. 7. Fenster L, Schaefer C, Mathur A, et al. Psychologic stress in the workplace and spontaneous abortion. Am J Epidemiol 1995;142:1176-83. 8. Windham GC, Von Behren J, Fenster L, et al. Moderate maternal alcohol consumption and risk of spontaneous abortion. Epidemiology 1997;8:509-14. 9. Rothman KJ. Modern epidemiology. Boston, MA: Little, Brown, 1986. 10. Hosmer DW, Lemeshow S. Confidence interval estimation of interaction. Epidemiology 1992;3:452-6. 11. Kline J, Stein Z. Spontaneous abortion. In: Bracken MB, ed. Perinatal epidemiology. New York: Oxford University Press, 1984:23-51. 12. Anokute CC. Epidemiology of spontaneous abortions: the effects of alcohol consumption and cigarette smoking. J Nat! MedAssoc 1986;78:771-5. 13. Harlap S, Shiono PH. Alcohol, smoking, and incidence of Am J Epidemiol Vol. 149, No. 3, 1999


Paternal smoking (cigarettes/day)

TABLE 5. Adjusted* odds ratios (OR) for spontaneous abortion (SAB) and amount of cigarettes smoked during pregnancy, California, 1990-1991

Tobacco Smoke Exposure and Risk of Spontaneous Abortion spontaneous abortions in the first and second trimester. Lancet 1980;2:173-6. 14. Guerin MR, Jenkins RA, Tomkins BA. The chemistry of environmental tobacco smoke: composition and measurement. Boca Raton: Lewis Publishers, 1992. 15. Jarvis MJ, Russell MAH. Measurement and estimation of smoke dosage to non-smokers from environmental tobacco smoke. E a r i Respirf>isr (Suppr) 1984; 133:68-75. 16. Haddow JE, Knight GJ, Palomaki GE, et al. Second-trimester

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serum cotinine levels in nonsmokers in relation to birth weight. Am J Obstet Gynecol 1988;159:481-4. 17. Bums D, Pierce JP. Tobacco use in California 1990-1991. Sacramento, CA: California Department of Health Services. 1992. 18. Office of Environmental Health Hazard Assessment Health effects of exposure to environmental tobacco smoke. Sacramento, CA: California Environmental Protection Agency, 1997.


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Vol. 149, No. 3, 1999