pared with never smokers. All former smokers had a 1.6-fold increase. but this increase was limited to those who had quit within the preceding 8 years. Longer durations of abstinence yielded an odds ratio of 1.0. Concerns about the possibility of differences in sexual activity between smokers and nonsmokers and the occurrence of STDs limit the ability to draw firm conclusions about the association of smoking with ectopic pregnancy. There is little information about former smokers, and consequently, no conclusion can be drawn. Some data suggest an association between smoking and increased risk of spontaneous abortion (US DHHS 1989). Data on smoking cessation are very sparse. Kline (1984) noted that the adverse effect of smoking observed in a case-control study of smoking and spontaneous abortion (Kline et al. 1977) was limited to current, not former. smokers. Alberman and colleagues (1976) found that the proportion of spontaneous abortions with abnormal karyotypes decreased with increased smoking but was identi- cal for never smokers and women who stopped smoking prior to pregnancy (Alberman et al. 1976). The interpretation of this finding is uncertain. Fetal, Neonatal, and Perinatal Mortality Information linking cigarette smoking with an increased risk of the various measures of mortality used to assess pregnancy outcome has been reviewed in previous reports of the Surgeon General and other publications (US DHEW 1979: US DHHS 1980: US DHHS 1986). Table 3 provides data on perinatal and neonatal mortality from the earlier reports of the Surgeon General (US DHEW 1979; US DHHS 1980) and adds informa- tion from a more recent publication on the topic (Rush and Cassano 1983). The studies are consistent in indicating higher mortality in children born to women who smoke. The high risk of mortality is independent of various factors. such as education and social class, that are also associated with mortality. Kleinman and colleagues (1988) assessed the effect of smoking on fetal and infant mortality in 362.621 births in Missouri during 1979-1983. Using multivariate statisti- cal techniques, these investigators estimated the effects of smoking on fetal and infant mortality among black and white primiparous and multiparous women. After adjust- ment for marital status. education. and age. fetal plus infant mortality rates were 25 to 56 percent higher in smokers for all categories of maternal race and parity. The elevations in the estimated risks of fetal plus infant mortality were statistically sig- nificant in all categories. In further analyses of data from the Missouri births and deaths, Malloy and coworkers (1988) showed that the relative risk of fetal plus infant mortality among whites was significantly elevated for the infants of women who smoked in all categories of low birthweight. even after adjustment for marital status. education, age. and parity (Table 4). This data set is unique in its size, consisting of more than 350,000 births. The data indicate that even in the normal birthweight infants of smokers—those that weighed 2.500 g or more-—mortality was significantly elevated for infants of mothers who smoked. Information on fetal, neonatal. and perinatal mortality in former smokers is sparse (Table 5). Butler. Goldstein, and Ross (1972) analyzed data from the British Perinatal Mortality Survey and estimated that perinatal mortality was the same for women who 376 TABLE 3.—Summary of studies of perinatal and neonatal mortality in smokers and nonsmokers during pregnancy Perinatal mortality" Neonatal mortality” Number of ~ Reference births Category = Smokers Nonsmokers Smokers — Nonsmokers Yerushalmy 6,800 Whites 13.4 124 (1964) Blacks 22.0 234 Comstock and 12.287 23.6 18.6" Lundin (1967) Amount smoked Meyer and 51.490 <1 ppd 28.0 23.0 Tonascia 21 ppd 33.4 (1977) Social class” Rantakallio 12.068 +I 2x4 22.4 (1978) HI+1V 25.1 19.6 Farmers 25.5" 39.0" Unknown 29.4" 36.8" Amount smoked Rush and <5 cig/day 15.9 18.7 Cassano 5—l4 cig/day 26.1 (1983) >15 cig/day 28.3 Butler, 21.788 All 32.0 17.6 13.7 Goldstein, Ross 1972) Amount smoked Andrews and 18.631 14 cig/day 25 24 McGarry 5-9 cig/day 20 (1972) 10-19 cig/day 32 220 cig/day 36 Race and Amount smoked Niswander 37,912 White 31.4 and Gordon 1-10 cig/day 31.5 (1972) 211 cig/day 38.2 Black 38.5 1-10 cig/day 41.5 211 cig/day 57.4 377 TABLE 3.—Continued ; / Perinatal mortality” Neonatal mortality" Number aft - Reference births Category Smokers Nonsmokers Smokers | Nonsmokers Race Rush and Kass 3.266 White 314 29.2 (1972) Black S4.1 28.6 Maternal age Fahia 6.879 <25 vr f6.4 12.1 (1973) 25-34 yr 13.2 12.6 235 vr 41.7 23.0 NOTE: ppd= pack s/day “Per 1.000: definition of mortality as in paper cited ” Adjusted for sex of infant and father’s education. “Defined in paper cited. \ ~ . “Rate based on five deaths or fewer. TABLE 4.—Estimated relative risk of fetal plus infant mortality for maternal smoking in several birthweight groups, adjusting for maternal marital status, education, age, and parity Birthweight Estimated group a) relative risk 95° Cl 500-999 171 1.46-2.00 1000-1499 1.78 L.S8-2.01] 1. 300-1.999 2.00 L&4-2.18 2.000-2 499 2.44 2.33-2,55 22,500 1.24 L.1Q-1.39 NOTE: Figures are for whites only. Cleconfidence inters al SOURCE: Malloy crak LYSso smoked prior to conception and who stopped before the fourth month of pregnancy as it was for never smokers. However. perinatal mortality was higher for continuing smokers than for never smokers for all categories of amount smoked. Andrews and McGarry (1972) examined mortality in the Cardiff birth survey of more than 18.6231 births. Perinatal mortality was 29 per 1.000 in those who quit smoking before pregnan- cy or inthe early months of pregnaney: 29 per 1.000 in continuing smokers; and 24 per 1.000 in “nonsmokers.” Rush and Cassano (1983) analyzed data from the 1970 British birth cohort. consisung of all births in Great Britain during a single week in 1970, Perinatal mortality among those who smoked before pregnancy but quit during preg- nancy (15.0/1,000) was lower than for either nonsmokers during pregnancy (18.7/ 1,000) or smokers of 5 cigarettes or more per day throughout pregnancy (26.9/1,000), TABLE 5. —Summary of studies of perinatal mortality in smokers throughout pregnancy, smokers who quit in the early months of pregnancy, and nonsmokers during pregnancy Perinatal mortality" , Number Smoked Reference of births Nonsmokers Former smokers throughout pregnancy Butler. Goldstein, 21.788 32.2 It cig/day 3n.7 I cig/day 38.5 Ross (1972) 5-9 cig/day 31.1 5-9 cig/day 42.2 10-19 cig/day 28.) 10-19 cig/day 41.6 20-30 cigdday 35,2 20-30 cig/day 41.2 Andrews and 18.631 24 29° 29 McGarry (1972) Rush and Cassano — 16.688 18.7 15.0" 26.9 (1983) “Late fetal and neonatal deaths/total births < 1.000, hb, . . 5 - . Women who quit smoking before the fourth month af pregnancy, ‘\ n who quit smoking before Pregnancy or during early pregnancy. d . \. anen who quit smoking during early pregnancy. Fetal, neonatal, and perinatal mortality are rare events. This limits the study of their association with smoking cessation. Lack of data makes it impossible to draw a firm conclusion about the association of smoking cessation with the risk of fetal, neonatal. or perinatal mortality. However, the limited available data are consistent with the conclusion that perinatal and neonatal mortality are lower among infants of women who quit smoking than among those women who smoke throughout pregnancy. The possibility must be considered that differences between women who quit smoking and those who continue to smoke account for the lower rate of perinatal and neonatal mortality in the studies in which this has been observed. Birthweight and Gestational Duration Introduction Fetal, neonatal, and perinatal mortality are the most direct measures of pregnancy outcome. Mortality is relatively uncommon, and very large samples are needed for study. This has led to the widespread study of birthweight and the percentage of births that are low birthweight (<2,500 &) as surrogates for the study of mortality. This strategy has been justified by the extremely strong association between birthweight and the percent of low birthweight and each of the measures of mortality (Figure 1). Equally important is weight at birth as a determinant of infant health (McCormick 1985}. 379 LOG RATE/1,000 3x80) 1000 x ‘ %*#—k Perinatal mortality = fetal deaths and neonatal . deaths/total births ha x x1 Neonatal mortality = ~ death through 28 days in ‘ . liveborn infants/live births LC O--O Fetal mortality = an stillbirths/total births \x a NX aN oN x Oe 100 + gh nN SON \ ON \ . \ Ky * N ON . ‘ \ x \ 10 o \ f KON ‘e an ‘N \ Ne 1 x Po T T T T T T 1 500- 1000- 1500- 2000- 2500- 3000- 3500- 4000- 749 1249 1749 2249 2749 3249 3749 4249 BIRTHWEIGHT (g) FIGURE 1.—Perinatal, neonatal, and fetal mortality rates by birthweight in singleton white males, 1980 SOURCE: Williams and Chen (1982). Birthweight is. however. a result of gestational age at birth and the rate of fetal growth, Recognition of the complex relationships among gestational duration. rate of fetal growth, birthweight, and mortality has led to attempts to classify infants according to gestational duration or joint distribution of birthweight and gestational duration. Generally. births are categorized as preterm (<37 weeks gestation) and/or as small for gestational age (SGA) (<10th percentile of weight for a given gestational age). Joint classification is thought to provide a more discriminating basis for the study of etiologic agents. Preterm delivery is strongly associated with increases in the risk of fetal. neonatal, and perinatal mortality and with significant childhood morbidity. Both preterm delivery and SGA increase the risk of cerebral palsy. although the risk is much greater for preterm delivery (Ellenberg and Nelson 1979}. SGA is associated with increased risk of neonatal and perinatal mortality at every gestational age (Koops. Morgan. Battaglia 1982: Lubchenco, Searls. Brazie 1972); with SIDS (Buck et al. 1989}: and with neurocognitive deficits, short stature, and small head circumference in childhood (Fitzhardinge and Steven 1972; Hill et al. 1984: Westwood et al. 1983; Ounsted and Taylor 1971; Harvey et al. 1982: Ounsted. Moar, Scott 1984. 1988: Fancourt et al. 1976). Continued Smoking As reviewed in previous Surgeon General's reports (US DHEW 1979: US DHHS 1980) and in other literature (Landesman-Dwyer and Emanuel 1979; Longo 1982: Werler, Pober, Holmes 1985: Kramer 1987), smoking during pregnancy decreases mean birthweight and increases the proportion of low birthweight births. Estimates vary among studies, but birthweight is reduced by an average of approximately 200 g. and the proportion of low birthweight is approximately doubled by cigarette smoking (Meyer. Jonas, Tonascia 1976: US DHHS 1980; US DHEW 1979: McIntosh 1984: Committee to Study the Prevention of Low Birthweight 1985: Kramer 1987). Mean birthweight decreases and the percent low birthweight increases with increasing num- ber of cigarettes smoked daily. The relationship between cigarette smoking and decreased birthweight is considered to be causal (US DHEW 1979: US DHHS 1980. 1989), Smoking affects birthweight and the percentage of babies who are born of low birthweight by retarding fetal growth. A measure of fetal growth retardation is the probability of delivering an infant who is in the less than LOth percentile for gestational age. The relative risk of SGA is about 3.5- to 4.0-fold higher among the infants of smokers than for the infants of nonsmokers (Ounsted. Moar. Scott 1985). Preterm birth ts also associated with maternal smoking. although not as strongly. Estimates of the relative risk of delivering before 37 weeks of gestation are typically about 1.5 for smoking during pregnancy (Committee to Study the Prevention of Low Birthweight 1985: Kramer 1987: Shiono, Klebanoff. Rhoads 1986). Mean gestational duration among smokers ts not significantly shorter than it is among nonsmokers (US DHEW 1979: US DHHS 1980). This finding is consistent with the observation that the risk of delivering early is greater among smokers than nonsmokers. but the percentage of 38] preterm deliveries is so small that the mean would not be affected unless the shift were very large (US DHEW 1979; US DHHS 1980). Cessation Before Conception Most studies of cigarette smoking and birthweight have failed to separate never smokers from women who quit smoking prior to conception. MacMahon, Alpert, and Salber (1966) first examined the association of pre-pregnancy smoking with birthweight and found no significant difference in the mean birthweight of infants whose mothers smoked before but not during pregnancy compared with never smokers. Subsequent research has confirmed the absence of an association between smoking prior to conception and reduced birthweight (Table 6). In all of these studies, smokers who quit before conception had mean birthweight values that were equivalent or higher than those of never smokers. Other studies in which information on mean birthweight could not be derived (Kline, Stein, Hutzler 1987; Anderson et al. 1984: Wainright 1983). with the exception of Zabriskie (1963), have also consistently shown no association between birthweight and smoking that ceased prior to conception. Zabris- kie (1963) failed, however, to adjust for smoking during pregnancy, and these results are not directly pertinent in a comparison of birthweight in never smokers and smokers who quit before conception. TABLE 6.—Summary of studies of mean birthweight, by smoking status Mean birthweight (2) Smoked before but Smoked Reference Never smoked not during pregnancy during pregnancy Cope. Lancaster. 3.376 3.395 3.200 Stevens (1973) Van den Berg 3.463 3.457 3,255 C1977) Rush and Cassano 3.357 3.384 NR (1983) Visnjevac and Miko 3,327 3,33] 3.097 (1986) NOTE: NR=not reported. In interpreting these data. misctassification of exposure needs to be considered. MacArthur and Knox (1988) reported that women who quit smoking during pregnancy. and possibly those who quit before pregnancy. were more often living with a purtner who smoked. Passive smoke exposure may adversely affect the fetus (Martin and 382 Bracken 1986). Furthermore, for whatever reason, some women may misrepresent their smoking status, denying that they have continued smoking, thus leading to an underestimation of the benefit of smoking cessation prior to conception. More important. women who quit smoking prior to conception differ in other respects from women who continue to smoke. Women who quit may have smoked fewer cigarettes per day prior to quitting. Studies of smoking cessation prior to conception have not accounted fully for other differences between women who quit and those who continue to smoke. Cessation After Conception Birthweight Table 7 summarizes nonexperimental studies in which information on mean birthweight in nonsmokers, smokers throughout pregnancy. and smokers who quit after conception could be derived. The data from each of these studies are consistent in two important ways. First, women who smoked throughout pregnancy delivered infants who weighed less than the infants of nonsmokers. Second. women who quit smoking delivered infants who weighed more than the infants of smokers throughout pregnancy. In most of these studies. mean birthweight values among infants whose mothers stopped smoking were the same or higher than those of infants of nonsmokers. Table 8 summarizes nonexperimental studies estimating the relative risk of low birthweight for continuing smokers and quitters some time during pregnancy compared with nonsmokers during pregnancy. These studies are consistent with those examining mean birthweight. Compared with nonsmokers. the risk of low birthweight is elevated among smokers throughout pregnancy, and the risk is about 1.0 for women who quit. In addition, Kleinman and Madans (1985) reported no association between the risk of low birthweight for women who quit smoking during pregnancy compared with those who had not smoked in the 12 months prior to conception among participants in the 1980 National Natality Survey (NNS). An important aspect of smoking cessation and pregnancy outcome is the timing of cessation during pregnancy and its relation to birthweight. How early in pregnancy cessation must occur to avoid the adverse effects of smoking on birthweight is a key issue with important implications for counseling pregnant smokers. In most of the studies examining this question, only information on cessation in the early months of pregnancy is presented. However. Rush and Cassano (1983) found that mean birthweight among women who quit as late as the seventh to eighth month of pregnancy was higher than for women who smoked throughout pregnancy. but lower than for nonsmokers and for women who quit earlier in gestation. MacArthur and Knox (1988) concluded that quitting any time before the 30th week of gestation increases birthweight when compared with continuing to smoke. Cooper (1989) assessed patterns of cigarette smoking by trimester of pregnancy. Women who reported smoking during the "first trimester of pregnancy only” had a 30-percent increased risk of having a low birthweight baby. while women who reported smoking during the "first and second trimester of pregnancy only” had a 70-percent higher risk of a low 383 TABLE 7.—Summary of nonexperimental studies of smoking cessation after conception, mean increase (+) or decrease (—-) in birthweight (g) according to timing of cessation Month of cessation Smoked Reference } 2 3 4 5 6 7 g 9 Unknown throughout Lowe +14 -182 (1959) Underwood et al. —108 -1S2 -230 (1967) Butler, Goldstein. +46 -160 Ross (1972) Andrews and —80 -170 McGarry (1972) Papoz et al. +10 -70 (1982) Rush and +98 +43 +36 -90 -155 Cassano (1983) Pulkkinen 61 -225 (1985) Counsilman and —40 —235 MacKay (1985) Kline. Stein. +12 -202 Hutzler (1987) MacArthur +22 —S8 242 and Knox (1988) NOTE: Mean increases or decreases are relative to nonsmokers during pregnancy. birthweight baby. Women who reported smoking throughout their pregnancy had a 90-percent increased risk of having a low birthweight baby in contrast to nonsmokers. Most fetal growth occurs late in pregnancy, and the primary smoke constituents considered as candidates in mediating the effect of smoking on fetal growth (.e.. CO and nicotine leading to intrauterine hypoxia) have short-term reversible effects. The data in Tables 6 and 7 support the conclusion that the adverse effect of smoking on birthweight occurs in the latter part of gestation, primarily during the third trimester. and that cessation at any time during gestation is likely to mitigate the adverse etfect of smoking on fetal growth. Because it is difficult to persuade all pregnant smokers to quit smoking entirely. the benefit of reducing the number of cigarettes smoked per day becomes a public health issue. The observation that cigarette smoking retards fetal growth in a dose-response 384 TABLE 8.—Summary of nonexperimental studies of relative risk of low birthweight for smoking cessation after conception Relative risk“ ? Ceased smoking Smoked Reference after conception throughout pregnancy Frazier et al. (1961) 1.0 17 Van den Berg (1977)" 1.6 3.0 Petitti and Coleman (in press) Whites 10 cigarettes per day). Using data from a longitudinal study of pregnant women, Van den Berg and Oechsli (1984) reported rates of preterm delivery (<37 weeks) among never smokers, smokers who stopped at the beginning of pregnancy, and continuing smokers for 10,947 white women whose singleton pregnancies progressed beyond 22 weeks. The rate of preterm delivery was 5.4 percent in never smokers, 6.8 percent in quitters, and 7.6 percent in continuing smokers. The difference in the rate of preterm delivery between never smokers and quitters was not statistically significant (p>0.05): however. the difference between never smokers and continuing smokers was significant. In a population-based case-control study of white and black women delivering singleton infants without congenital anomalies in a large urban county. Petitth and Coleman (in press) reported that the estimated relative risk of very low birthweight (<1.500 g) or of other preterm births among black and white women who quit smoking prior to the fourth month of gestation was not increased in comparison with those of nonsmokers. The estimated relative risk of very low birthweight (<1.500 g) in continu- ing smokers was 2.5 tor whites and 3.1 for blacks and that of other preterm births was 2.0 for whites and 3.7 for blacks, MacArthur and Knox (1988) examined gestational duration according to smoking during pregnancy. Mean gestational length was 1.7 days shorter among continuing smokers than nonsmokers. Compared with nonsmokers, gestational periods were 0.4 days shorter for women who quit smoking by the 6th week of pregnancy, 1.5 days longer 386 for women who quit between the 6th and 16th weeks of pregnancy. and 0.3 days longer for women who quit after the 16th week of pregnancy. Because of the limited data on the risk of preterm delivery among women who quit smoking after conception, a firm conclusion about benefit. or lack of benefit. at- tributable to smoking cessation for this pregnancy outcome cannot be drawn. Complications of Pregnancy Women who smoke during pregnancy are at increased risk of bleeding during pregnancy and of placenta previa and abruptio placentae (US DHEW 1979: US DHHS 1980; Naeye 1978: Naeye 1980). These women are probably at decreased risk of preeclampsia (US DHEW 1979: US DHHS 1980: Marcoux, Brisson, Fabia 1989). Few data on these pregnancy complications among former smokers are available, In Naeye’s (1980) analysis of data from the Collaborative Perinatal Project, smoking for more than 6 years (but not short-term smoking) was found to be associated with a relative risk of 1.6 to 1.9 for abruptio placentae and a relative risk of 2.4 to 2.8 for placenta previa. Women who had stopped smoking by their first prenatal visit were not at increased risk of abruptio placentae, but were still at twofold increased risk of placenta previa if they were long-term smokers. However, the latter result was based on only 18 exposed cases. Marcoux, Brisson, and Fabia (1989) found that, compared with women who had never smoked, those who smoked at the time of conception were protected from preeclampsia (estimated relative risk (RR)=0.51), whereas women who smoked but quit prior to conception had the same risk of preeclampsia as never smokers (RR=0.97). Women who smoked at conception but quit prior to 20 weeks’ gestation were not as protected from development of preeclampsia as were continuing smokers. Because of the otherwise serious adverse effects of smoking on the fetus, this minor “benefit” of smoking during pregnancy probably has no public health consequence. Randomized Trials of Smoking Cessation During Pregnancy Three randomized trials have been conducted on pregnancy outcome in relation to advice to stop smoking (Donovan 1977; Sexton and Hebel 1984; MacArthur, Newton, Knox 1987). Table 9 summarizes the studies and birthweight results. Two other randomized trials have also been conducted on the effect of various programs on smoking cessation rates among pregnant women (Ershoff, Mullen, Quinn 1989: Windsor et al. 1985), and other trials are in progress. Information on pregnancy outcome is not available, and these studies are not reviewed. Donovan (1977) studied smokers in three matemity units in England. Women aged 35 years or younger at the start of pregnancy, who smoked more than 5 cigarettes per day, who had less than 30 weeks of gestation at the first prenatal visit, and who had no prior perinatal deaths, were randomly assigned to a control group that received usual prenatal care or to a test group that was given intense individual antismoking advice by a physician at each prenatal care unit. There were 263 women in the test group and 289 in the control group. Mean daily cigarette consumption decreased from 17.1 cigarettes per day early in pregnancy to 9.2 cigarettes per day late in pregnancy in the intervention IR7 for women who quit between the 6th and 16th weeks of pregnancy. and 0.3 days longer for women who quit after the 16th week of pregnancy. Because of the limited data on the risk of preterm delivery among women who quit smoking after conception, a firm conclusion about benefit, or lack of benefit, at- tributable to smoking cessation for this pregnancy outcome cannot be drawn. Complications of Pregnancy Women who smoke during pregnancy are at increased risk of bleeding during pregnancy and of placenta previa and abruptio placentae (US DHEW 1979: US DHHS 1980. Naeye 1978: Naeye 1980). These women are probably at decreased risk of preeclampsia (US DHEW 1979; US DHHS 1980: Marcoux, Brisson, Fabia 1989). Few data on these pregnancy complications among former smokers are available. In Naeye’s (1980) analysis of data from the Collaborative Perinatal Project. smoking for more than 6 years (but not short-term smoking) was found to be associated with a relative risk of 1.6 to 1.9 for abruptio placentae and a relative risk of 2.4 to 2.8 for placenta previa. Women who had stopped smoking by their first prenatal visit were not at increased risk of abruptio placentae, but were still at twofold increased risk of placenta previa if they were long-term smokers. However, the latter result was based on only 18 exposed cases. Marcoux, Brisson. and Fabia (1989) found that, compared with women who had never smoked, those who smoked at the time of conception were protected from preeclampsia (estimated relative risk (RR)=0.51), whereas women who smoked but quit prior to conception had the same risk of preeclampsia as never smokers (RR=0.97). Women who smoked at conception but quit prior to 20 weeks’ gestation were not as protected from development of preeclampsia as were continuing smokers. Because of the otherwise serious adverse effects of smoking on the fetus, this minor “benefit” of smoking during pregnancy probably has no public health consequence. Randomized Trials of Smoking Cessation During Pregnancy Three randomized trials have been conducted on pregnancy outcome in relation to advice to stop smoking (Donovan 1977; Sexton and Hebel 1984; MacArthur, Newton. Knox 1987). Table 9 summarizes the studies and birthweight results. Two other randomized trials have also been conducted on the effect of various programs on smoking cessation rates among pregnant women (Ershoff. Mullen, Quinn 1989; Windsor et al. 1985), and other trials are in progress. Information on pregnancy outcome is not available, and these studies are not reviewed. Donovan (1977) studied smokers in three maternity units in England. Women aged 35 years or younger at the start of pregnancy, who smoked more than 5 cigarettes per day, who had less than 30 weeks of gestation at the first prenatal visit, and who had no prior perinatal deaths, were randomly assigned to a control group that received usual prenatal care or to a test group that was given intense individual antismoking advice by a physician at each prenatal care unit. There were 263 women in the test group and 289 in the control group. Mean daily cigarette consumption decreased from 17.1 cigarettes per day early in pregnancy to 9.2 cigarettes per day late in pregnancy in the intervention 387 TABLE 9.—Summary of birthweight outcome in randomized trials of smoking cessation in pregnancy Number of Smoking at end subjects of pregnancy Birthweight (g) Reference ( c ! Cc ] Cc Difference ¢gy" Donovan (1977) 263 289 ¥.2cig/day 16.4 cig/day 3.1720 3.184 +12 Sextonand Hebel = 463 472, 57.0% 80.0% 3.278 3.186 +92 (1984) MacArthur, Newton, 493 49 OIG 94% 3.164 3.130 +34 Knox (1987) NOTE: I=intervention group: C=contrel group. “Mean in intervention minus mean in control, group. but increased slightly from 14.7 to 16.4 in the control group. Mean birthweight was 3,172 g in the test group and 3.184 g in the control group. In the test group 10 percent of the infants had low birthweight (<2,500 g) compared with 9 percent in the control group. There were four perinatal deaths in the test group and one in the control group. None of the differences in birth outcome between the test and control groups were statistically significant. Although this trial might be regarded as evidence against a benefit of smoking cessation during pregnancy. a number of limitations of the study must be considered. First, no data are presented concerning the percentage of pregnant smokers who quit smoking entirely. Reducing cigarette consumption almost certainly has a smaller benefit for pregnancy outcome than complete cessation. Second. the time at which smoking behavior changed during pregnancy is unclear; data on cigarette consumption for three periods during pregnancy were obtained postnatally, and may have been affected by recall bias. Data from observational studies discussed in the previous section strongly suggest that smoking during the last trimester of pregnancy is a critical mediator of reduction in fetal growth among smokers. Information from another British randomized trial (MacArthur. Newton, Knox 1987) also questions the benefit of smoking cessation during pregnancy. In this study, women who smoked at the time they were scheduled fora prenatal visit at a large hospital were assigned randomly to a control group that received routine care or to an intervention group that received supplementary health education about smoking during pregnancy. The planned intervention consisted of advice to stop smoking and information about the effects of smoking on the fetus. presented visually by a booklet or verbally by the obstetrician. There were +89 women in the control group and 493 in the intervention group. Mean birthweight for infants in the control group was 3.130 g¢ compared with 3.164 g for the intervention group. The percentages of low birthweight and perinatal mortality in the two groups were not reported. The difference in mean birthweight was 388 not statistically significant as determined by the conventional 0.05 probability value and a two-sided test. In this trial, only 9 percent of the women in the intervention group quit smoking entirely. compared with 6 percent of the women in the control group. The failure of the intervention to cause smoking cessation makes this trial essentially uninformative concerning the benefit, or lack of benefit. of smoking cessation during pregnancy. In the intervention group, 28 percent of the women reduced the number of cigarettes smoked per day, compared with 19 percent of the women in the control group. The greater reduction in cigarette consumption in the intervention group. in the absence of a difference in mean birthweight between the intervention and control groups. suggests that reducing smoking does not entirely prevent the adverse effects of smoking on birthweight. The third randomized trial (Sexton and Hebel 1984) recruited women in a large metropolitan area from various sources. Smokers of at least 10 cigarettes per day at the beginning of pregnancy, who had not passed the 18th week of gestation. were randomly assigned to a control group that received routine advice or to a treatment group that received intensive, ongoing advice throughout pregnancy from specially trained profes- sional staff. There were 472 women in the control group and 463 women in the treatment group. The mean birthweight of infants born to women in the control group was 3.186 g compared with 3,278 g for infants of women in the treatment group. The “percentage of low birthweight infants was 8.9 in the control group and 6.8 in the treatment group. There were If stillbirths in the control group and 9 in the treatment group. The difference in mean birthweight was statistically significant (p<0.05, two- tailed test); the differences in the percentages of low birthweight and in fetal mortality were not statistically significant. In this trial, 43 percent of the women in the treatment group had ceased smoking entirely by the eighth month of pregnancy, compared with 20 percent of the women in the control group. The intervention was, therefore. highly successful in causing substantial changes in smoking that exceeded changes in the comparison group. The investigators ruled out concomitant changes in consumption of alcohol and coffee as explanations for the increase in birthweight. Weight gain was 1.0 kg greater among the treatment group than the control group, but at least part of the difference in wei ght gain was a result of the higher birthweight of the infant (Sexton and Hebel 1984). Review of these three randomized trials leads to two conclusions. First, to prevent entirely the adverse consequences of smoking on birthweight. it is necessary for women to cease smoking completely. Second. intensive interventions spanning the entire period of gestation may be necessary to effect large changes among the percentage of women who abstain from smoking entirely. 389 Prevalence of Smoking and Smoking Cessation During Pregnancy and Time Trends in Prevalence and Cessation Introduction Ideally, conclusions about the prevalence of smoking during pregnancy and trends in prevalence would be based on representative samples of pregnant women performed at regular intervals using the same methodology. Assessment of smoking cessation during pregnancy and time trends in smoking cessation should be based on repre- sentative samples of women who start pregnancy as smokers and who are monitored for smoking behavior throughout gestation. Available data fall short of these ideals. Furthermore, available information on smoking and smoking cessation in pregnancy is based almost exclusively on self-reported behavior. Few data on the quality of self-reported smoking specifically in relation to pregnancy have been collected, and it is possible that the societal pressures against smoking during pregnancy would make underreporting more problematic than for other populations (Chapter 2). Similarly, pregnant smokers who admit to smoking might underreport their daily cigarette consumption. perhaps to a greater extent than nonpregnant smokers. The effect of underreporting of smoking and overreporting of cessation would make the data from former smokers more similar to that of continuing smokers with respect to their reproductive health outcomes. Also. smokers who reduce the amount of nicotine in their cigarettes by changing brands or those who reduce the number of cigarettes they smoke per day without quitting may compensate to maintain the same nicotine dose (US DHHS 1988). Prevalence of Smoking and Smoking Cessation Pertinent data on smoking during pregnancy from the 1985 National Health Interview Survey (NHIS) (NCHS 1988) are presented in Table 10. The 1985 survey focused on health promotion and disease prevention. The survey involved nearly 35.000 households and more than 90.000 persons. and the response rate was 95.7 percent. Information concerning smoking during pregnancy was obtained from all female household members aged 18 to 44 vears who had had a live birth in the 5 years prior to the survey. The proportion of women who had smoked at any time during the year preceding pregnancy was 32 percent overall. Of women with less than [2 years of education, 46 percent smoked in the year preceding pregnancy, compared with 13 percent of women with |6 or more years of education. Thirty percent of married women had smoked, compared with 40 percent of formerly married women. Patterns of smoking cessation or reduction were reported in detail for some demographic subgroups. Overall. 21 percent of women who smoked prior to pregnane.s quit upon learning of their pregnancy. and an additional 36 percent reduced the number of cigarettes they smoked. Cessation (but not reduction) was strongly related to education and family income. Among women with less than 12 years of education, 12 years of education, and more than 12 years of education, [5, 20. and 32 percent quit. 390 TABLE 10.—Smoking and smoking cessation during pregnancy, summary of results of two surveys of national probability samples Percentage of pregnant women Quit upon learning of pregnancy Smoked Reduced Educational attainment (yr) Study before amount 5 (vr) pregnancy — smoked All