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C~INICAL TOXICOLOGY, 18(2), pp. 189-~o9 (198i) Cigarette Smoking and the Outcom-e 6f Human Pregnancies: A StatusReport on the Consequences CR, AIG JOHNSTON Department of Pharmacology and'T~xicology Michigan State University East Lansing, Michigan 48824 Although the media have saturated the general public with anti- smoking campaigns primarily focused on lung cancer, pregnant women as a target group for antlsmoking efforts have been r.elatively neglected. This oversight is perpetuated despite the fact that expectant mothers might be highly.responsive to an effective program capitalizing not jUSt . on effects that smoking can have on the expectant mothers themselves but that also helps them realize that their unborn baby' s health is im- periled. Education about the effects of smoking on the outcome of pregnancy may have been lagging partly because, until recently, the effects of maternal smoking On the outcome of pregnancy were not hs. welt defined a~ the effects of smoking on the cardiovascular and respire-. tory'systems. In fact, a national sample survey reported that less than two-thirds of youn[~ women smokers believe that smoking can harm an unborn child, a figure to he comparedwlth the 90% of adults who believe that smoking is harmful to their own bodies [1]. This review will attempt to.summarize the present state of knowledge re'garding the effects (proven and ptitative) of maternal smoking On the outcome of human pregnancies. Some of the controversies, questions, problems, and cautions that must be taken In evaluating these effects will be discussed. The subject is further complicated by the fact that tobacco smoke has a complex composition consistin.g of hundreds of chemical compounds. Some of the major compgnents are [2] : Copyr[l~ht 0 1981 by M~tgcel Dekkcr. Inc. 189 1S503 T104231150

190 JOHNSTON i. Nicotine is probably .the constituent that smokers become d.e- 'pendent upon, and includes in its actions both s'tlmulatlgn and l~hibition of the nervous"system depending on the dosage. When absorbed from smoke, it can stimulate or tranquilize, re~ching • the brain within a minute after the first inhalatlon of cigarette sn~oke. Furthermore, ~iicotine can adversely affect the heart.. and blood vessels in several ways. • " ". 2. Carcinogens in ~he tar fraction of tobacco smoke c~n ~ause cancer when applied to the skin or lungs of "animals. 3. Carbon monoxide (CO) ~onstitutes about 1-5% of tobacco smo~e • -a.ud can ~ombine with up to 15% of the hemoglobin to form car- box'yhemoglobin (COHb) in a s/uoker due to the large affinity • that the red blood cell hemoglobin has for CO, thu.a making it unavailable for carrying oxygen. • ' 4. Irritant .substances, which cause bronchial tube narrowing, in- hibit the ~earing action of c.ilia and stimulate excessive secre- tion of mucous. "' ... An atte.mpt will be made to attribute the e~.fects under .consideration to that component Of tobacco smoke, thought to be r~sponslble whei:ever it is known, and.to describe proposed mechanisms where appropriate.. ,. ','EFF~CT.S O'F MATERNAL S.MOKING " • Fetal Growth" .... Concern over the effects whic~ cigar.erie s. moking might have on. the developing conceptus of smoking mothers has grown evei: since the 1920s when smokingbecame more popular among women. If maternal • smoking was .harmful to an unborn child, one might ~xpectthat the ." "average vitality of chi.ldren b~rn to smoking motherS, would be reduced. Accepted indices for the vitality of offspring .include (1) mortality rate, (2) incidence of deformities, (3) incidence of prematurtty, and (4) the relattv~e rate of growth [3]. The first evidence from human s.ubJects that smoking reduced the inherent vitality of infants was provided by- Simpson [4] in her.study of.7499 pregnant patients. It was found, that babies born to women who smoked duridg pregnancy were ~n the aver- age 200 g lighter than neonates born to nonsmokers. Many physiologic factors influenc.e fetal growth including fetal sex, maternal age a~d parity, race, ethnic background, parental size and stature, as w#li as immunological factors such as fetomaternai hlstolncompatibiiity Soon after Simpson~ s report, Lowe [6] published a more comprehen- sive analysis which dealt with many of these potentially con~ounding variables. Among the factors considered were maternal age, parity, prepregnant weight, and geatational duration. This study not only con- [lr.m .~]ti a reduced birthweight that withstood all attempts at ~tatiatical ad|ustments for confounding variables along with a d0ee-respon~e 't TI04231151

CIGARETTE SMOK~ AND HUMAN PREGNANCIES "~ .191 relationship., b~t the analysis further sho~ed that early cess'ation of smoking minimized harmful effects to the fetus. The observations " . and conclusions of SimpSon an~d Lowe have been confirmed in the last 20 years in more than 230 articles [7], more than 40 of which have appeared since 1975 [2-5, 7-57]. This has led to the general accep- tance that smokerst babies weigh o~ the average 170~200 g less than nonsmokersf babies (range: 120-430 g), and thaiabout twice a~ many in the 'former group weigh less than 2500 g at birth., There is a signi- ficant dose-response relationship, and it ha.s been calculated that i~i a . pregnancy o5 normal duration the decrease in birthweight would be 8-9 g for e.ach cigarette smoked daily [2], Despite'the ~vide ~greement that maternal smoking decreases birthweighl, the,cause ofthe growth re-" tardation in ute~o i~emalns a highly controversial matter. Because cigarette smoke is chemically very complex, there are many poa.stbiit- ties for modes of action [2, 7, 24]. •Among these are: 1. An effect.of nicotine on uterine vessels Which may price plac'~r/- .. tat wsoconstriction [58]. : . ". 2. A direct action of nicotine on .the fetus which may result in ac- celerated fetal metabolism and a greater need for nutrients [59]: • 3. Increased concentrations'of CO in cord blood that c~utd result • • in (a) decreased carbonl~ anhydrase activity [60]', (b) ~lir~t placental effects [61], and (c)chronic fetal hypoxia associ'ated width increased.levels of COHb [3,.29, 62-66]. • • - " • 4, A direct effect on the fetus of some toxic agent l~cigarette.sm.oke whose chemical nature remains to be defined. 5. A decreased avatlal~tlity of l&por.tant nutr[en'ts.s'uch a~" amino acids and zincf61] which axe possibly related to thb detoxifica-' lion of cyanide [68]. ~. .- 6. Reduced maternal weight gain due to a decrease in the appetite andcaloriC intake .among smokei~s [69].., 7, An impaired immune response associated with increased mater-~ nat urinary tract and viral infections [70]. • ' 8. Hormonal effects which, cause an increase in Contractility of ' uterine smooth muscle during smoking which disappears upon cessation of smoking [2.~]. This is probably not a direct e~fect of nicotine on uterine mdscle, but.is believed to be due to its • actions on the CNS. resulting in the release oJ[ oxytocin which causes contractions of the uterus• and thereby reduces uterine and placental blood flow [30, 34, 40, 51]. • The ~vailable published information primarily supports (1) a direct effect o! nicotine [14, 21, 22, 32, 42, 71, 72] and/or carbon monoxlde as factors causihg intrauterine hypoxi~, and (.2) a #educed maternal weight gain [13, 17] resulting from a decreased caloric intake as the two most likely mechanisms for the effect of smoking on birth weight. Supporters of the "n~trltlomfl" explanation have found habitu~d smokers (defined as any degree of tobacco use) to weigh less than habitual nonsmokers {women'~eported smoking during one pregnancy but abstinence from T104231152

• -192 JOHNSTON. Smoking during subsequent pregnancies) [17]. Furthermore, habitual nonsmokers have been shown to galh on the average an additional 1- "i 22 Ib between pregnancies th~n habitual smdkers. In mother study the" monltori~g of.body .welghk in obese smoking mothers did not Yeveal the "smoking effect" when compared with smoking mothers as a group or " • nonsmoktng mothers [13]. Rather, obese smoking mothers in this study resembled nonsmoking mothers in gestation length and birth- " • • weight as welt as birth wetght;correlated to gestatio~ length.. This ap' ...... parent counteraction of the smoking effept on fetal weight by weight-• deflned.maternal bbeslty was seen even sfterparity, socioeconomi~ . status, prepregnancy weights, maternal age, "and stature were taken into account. This evidence would seem to suggest a nutritional cause • for many of tl~e deleterious effects of smoking during pregnan.cy on fetal dev.elopment... However, it Is possible that, obese mothers haye larger placentae and t hat the increased placental size is the simpllstic explanation [73]. :. ; Evidence. .~upporting the hypothesis of a direct.effect of some com-~ ponent of cigarette smokeappears quite convincing, Studies have re= por.ted acute decreases in tntervttlous placental blood flow after smok- ing a single standard eigarett~ [29]. On the basis 'of such obser.vations • it was postulated that •this brief effect, when rbpeated several times, .. • might b~ harmftil to thd fetus.~ .The investigators concluded that this actlon probably resulted from vasoconstrictiOn ofthe, uterine vdssels by nicotine. "Furthermore, they assumed that when added to the for- mation of COHb tn th'e fetus (a level ot 9% COHb tu the fetus ts pre- .sumably eqdivalent to a 41% re.ductton bf blood flow or hemoglobin . concentration in the umbilical vein [~4] )," the blood fl0w Impairment might explain why fetal growth retardations ar.e more fre~luent among smokers than nonsmokers. " In another, study a reduction of the birth- weights of children.delivered by mdthers who smoked during preg' • nancy was confirmed without observing a significant difference in either maternal weight increase or extratiterlne weight gain Ultrasonic me.asurements of the fetal bipaxietal diameter (BPD) from the 18-20th week until term demonstrated teat the BPD increased faster during gestation in thd nonemoklng group, Thd difference com- pared'to the smoking group wa~. significant f~om the ZSth week onward and positlvely.correl.ated with the average number of Ctgarett~s smoked. - [42]. The low blrthweight~ were independent ~f maternal prepregnancy weight as well as weight gain during pregnancy and aripeared to be a matter of general size reduction and not of simple wasting. Decreases in birthwelghts among babies of smokthg mothers compared to babies • of nonsmoking mothers independent of the mother's height, weight, - hospital status, age-parity group, birthplace, previous pregnancy his- tory, weight gain, time of registration, sex o! chll~, socioeconomic status,-gestational.lengih, race, education, and nuptial status of the birth have been demonstrated [11, 14, 34, 46]. A unique study by Germ.sex et al. [19] looked at the influence o! maternal smoking on fetal breathing movements and attempted to dlfferentia~e between the" role that CO and nicotine play in this response. ~T~eatments consisted Ti04231153

• CIGARETTE SMOKING AND HUMAN PREGNANCIES 193 of a Standard "cigarette meant to increase COHb and blood nicotine, a nontobaceo cigarette which raised only COHb, and two nicotlne:con- raining chewing gums whihh lncreabed the blood nicotine levels to two different concent.ratlons without affecting the COHb levels. Nicotine • tended to reduce fetal breathing movements In a dose-dependent man- ner, whereas the rise in COHb alone did not affect the amount of fetal breathing m.ovements. TWO studies in particular strongly favor the vfe~ as regards R . direct effect. Meyer [32] investigated the possibLtity that maternal smoking during pre~ancy caused low birthwe~ghts by reducing mater- nat appetite, thus reddclng food int.ake and weight gain. Several subgroups of differing smoking• intensities, maternal weight gain, birth- weight, and gestation were formed from over 51,000 births. Maternal .weight gal.n distributions were the same for sm6kers and nons.m.okers, while within each level of maternal weight gain, ranging from less than 5 Ib to over 40 Ib~ it w~s found that the more the mothers smoked the greater the percentage of neonates .weighting less than 2500 g. Naeye [40] applied a novel method of analysis by using mothers who had smoked during one pregnancy, but not during another, to nearly 47,000 single born infants. He found that mothers gave birth to smaller in., rants durlhg the pr~g~.'andy in which they smoked, irrespective of birth • order and many o~her factors that affect fetal growth. Consideration was given.to duration.of pregnancy, maternal weight gain, and its. dis- trlbution between mother, fetus and placenta, birth•order, mother's ' age, race, her prepregnan.cy weight, height, socioeconomic status, terval between pregnancies,'anaemia.in either'the mother or the infant, and sex of the infant." Furthermore, he examined the placentae and fo~und that, as smoking intensity rose, placentae were enlarged and de- veloped microscopic lesions characterlsdc of poor perfusion. He sur- mised this underperfusion to b~ perlo~, ic rather, than continuous beca/me the smokers' dectdua contained few of the arterial lesions characteristic "for chronic low blood/low. In summ~ry, it appears.|ustified to conclude that maternal smoking daring pregnancy emerges as the most important single avoidable determinant of low b.irthweights, Despite the evidence cited above, an.other group of tnvestlgato'rs has • "questioned the causal relationship between maternal smoking.and deo creased birthweights [I0, 48, 49, 56-67~ ~5], Most outspoken was Yeru~ shalmy who maintained that this effect w~s spurious and merely an in- dicator of lower class which is also commonly a~sociated wi[h ~educed birthwelgi~ts [56, 57] Yerushalmy intervie~ved 10,000 white And more than 3,000 black women during early pregnancy, probing a variety of . • medical, genetic, environmental, and behavioral variables. In his study, condt~cted in the East Bay area of San Francisco, Yerushalmy found great differences in life-style between smokers and nonsmokers. Fur- thermore, although the mothers' cigarette smoking Increased the pro- portion of lo~voblrth weight in/ants, these low-birthweight babies were .supposedly healthier tliam tho~ie of the nonsmokers. Smoking fathers ~.also causect a $onYewhat higher incidence of low-birthweight infants, but J TI04231154

II ! 194 JOHNSTON the prognosis for these, tnfahts w~s presumably poor with higher nee-.. natal mortality rates and incr.eased risk for kevere cor~enital anom- alies. Yerushalmy proposed that such paradoxical findings ~s.well as the fact that mothers determined whethe~ they'belonged to the smoking or.nonsm~king group (viOlating the basic rule for.valid • scientific inference that, a priori, groups being compared be alike in all pertinent characteristics) suggested that cigarette smoking may not be a determinant- affecting fetal development. Ye~t~shalmy [57] also explored the question as to whether the increase in birthweight infants '~uong smoking gravidas was .due to the ~mokifi~ or the smoker by investigating the r.eproductive performance of future smokers during the periods before they acquired the smoking habit, Women who in subsequent pregnancies became smokers had a high incidence of low-birthweight infants even beforethe~ ever started'to smoke.. He concluded that the findings-rats'ed serious doubts and argued against the proposition that cigarette smoking acts a~ an ex- " ogenous factor that interferes with the intrauterine development of the fetus. Yerushalmy's interpretation was that the higher incidence' of low-birthweight infants is due to the smoker, not the s.mokingi Yerushalmy' s findings r'~late 0nly to. a single stt~dy. The sample sizes in his and other studies supporting his findings [10] a~'e not large enough to investigate the role of correlated variables, The criticism that the ha~mfu! effects of smoking are now so weil'pubil~ cized that. some smokers may deny the habit, thus diluting the control group~ may also apply. An excellent treatment of the logic behind Yeruehalmy's arguments is ~found in the book Smoki_ng, Health" and Personality [49]. Problems also exist in Yerushalmy's definition of ."smokers'! as women who were smoking one or more cigarettes per day during pregnancy,, and "nonsmokers" as women who never smoked or those who stopped smoking either before or during pregnancy. Be- cause the smokihg history was obtained only once, usually during early ~regnancy, some of the participants classified as ~'sinokers" could have gone through a sigulflcaut portion of their pregnancy as '*non- smokers" and vice versa, so that a decline of the magnitude of any dif- ferences found could have occurred. MacMahon et aL [47], commenting on Yerushatmy;s ~alysls Of rn0rt~lity rates in low-birthwelght observed that there are "factors that affect bi~thweight without influenc- ing mortality; for example, females have lower b|rthweights than m~les but not higher m~rtallties that might be predicted for them on that account. If cigarette ~moking is another such factor, the e~planation of the higher. . weight-specific mortalities for nonsmokers becomes immediately clear.'. • it ts an artifact of the analysis. It is meaningful to d0mPare categor~- specific rates on_.~_when the specification of the category ha~ the same implication of the populations compared." Goldstein [21] noted that the data in Yerushalmy's paper on ~moking habits were obtained retrospectivelyby going back over a number of years. The possibility cannot be discounted that many of the mothers who were classified as becoming smokers only after their babies' birth.might in fact have been smoking d~ring pregnancy. In addition, Ti04231155

oo CIGARETTE SMOKING AND HUMAN PREGNANCIES 195 .the mothers who smoked not only had their first baby before they were 25 years old, but actually started smoking before that age. This im- plies that they had their first babies "at younger ages than those mothers who had never smoked .under 25 years. In fact, they were on the a~er- age about 2 years younger tn'Yerushalmy's study. Moreover, several reports, including the one by Yerushalmy, have shown that the propar- lion of low btrthwelght babies born t~ mothers under 20 years is about 20-25~ higher than among mothers aged between 20 and 24 years. Hence a proper age standardization Would be necessary before drawing any conclustbns. Finally, the fact that mothers .who give up smoking by the fourth month of pregnancy have a risk similar to that of a nonsmoker of delivering a low birthweight infant [16~ 71] r while mothers who begin smoking at that time have smaller neonates [16], further implicates tobacco smoking per se rather than any .constitutional proclivity tn the . etiology, of small neonates. Other mechanisms for fetal growth retardation under discussion in- c.tude one proposed by Pettigrew et at. [44]. These investigators pro- posed a mechanism by which cyanide and p~reformed thiocyanate which. • "enter the body as contamlnants of foodstuffs and tobacco smoke reach the body fluids, cross ttie placenta, and al~pear in blood and urine of ,.. babies born to smokers. The detoxtftcation of cyanide increases the requirements for vitamin BA= and sulfu~ amiho acids ~in both mother• and fetus. This may In part explain the reduced birthwetght of the babies. Plranl et al. [45] postulated:that smoklnghad dotrlmental el-. • fects on maternal body composition which manifests itself in "poor overall performance with the consequent p~oductton of Smaller infants~" Harrison and McKenna [23] founds Significantly lnEre~sed mean'cor- puscular volume and blood viscosity in both smoking mothers and their newborns. Such alterations could result in decreased maternaJ and • fetal p~lacentai blood fl0w,.thus redu'cing the fetal growth rate and eventually the lnfantts birthweight. Interestingly, Boyce et at. [78] "found significantly lower human placental lactogen levels (general-ly credited as a useful indicator of placental function and integrity) in • smokers .than in nonsmoking controls. However, they found no rela- • tionship between birthweight arid smoking when human placental lass- • gen was held constant, suggesting a role for human placental lactogen tn the birthweight effect'. " A new perspective has been revealed concerning the question of" fe~al growth retardation in relation to maternal smoking by the find- • lngs of Miller et al. [36]. Their observations" and interpretaiions ira- , ply that there may be two independent types of fetal growth retarda- tion. One is. characterized by an abnormally low ponderal index (birth- ; weight in grams x 100 :-- crown-heel lengtli in cubic centimeters) and is associated with mothers who experience low weight gain during • pregnancy. The other type displays.abnormally short crown-heel. • length for fetal age and occurs' among mothers Who have smoked ~ cigarettes during pregn~ .ancy. Perhaps the controversies will be ~.=ett ..t~d .s~on. o • T104231156

196 . JOHNSTON Iutervlllous Blood Flow of Placenta~and • Investigations have demonstrated increases 1~ placental complica- - "" lions associated with incre.ases in smoking level tndependegt of the ' • mother's height, weight', hospital status, age~parity group, birthplace, ' . previous pregnancy history, weight gain, time of registration, and sex ~ ~.*.!~. of child [7, 35, 39, 40, 5.0, 79-81].• in one study placental com'plica- • "tions increased consistently with smoking levels in a~l of .3.7 subgroups " :'.~: e~cept for primiparous < 1 pack per day Smokers [34], Presence of " ":. placenta precis increased 25 and 92% and abrupti0 placentae Increased 23 and 86~o among smokers of < 1 pahk and 1 or more packs~ respeC- tively. High perinatal mortality ~lsks are associated with these com- plications which reportedly account for one-third to one-half d~ the,.. occurrence of placenta precis and abruptio placentae are h,igher for smokers than nonsmokers at all gestational lengths wi.th relati.v~.ly larger differences in the earlier weeks of preghancy [35], In a study " of almost 47)000 placentae, Naeye [40] offered a histologic~l explana- tion ~or the placental hypertrophy associated with tobacco smoki.~g oc- curring in the.absence of lesions that would explain retarded fetal growth [55, 66, 82]. As smoking level increased, placentae• enlarged and developed microscopic.lesiOns characteristic o! underpe~fusion • from the uteruS, such as obtllter~tive endarterttis .and cytotrophoo '. blastic hyperplasla in villi.and "necrosis of the decidua basalis at margin of. the placenta. Because. the smokers" decldua had iew o~ the. • arterlat lesions that are characteristic of chronic low blood flow,. .' Naeye concluded that th~s underperfuston was probably periodic rather than continuous. Nicotine via its acute effect o~ reducing lntervillous placental blood flow [29] could cause such .a periodic uteroplacental underperfusion. Since the commoftest cause o~ placent~ enlargement .. besides ciga~ette smoking is hypoxta resulting from reduced oxygeh- carrying capacity of fetal or maternal blood or low oxygen saturation . " o! maternal arterial blood, the increased levels o! COHb In the blood of smokers [62," 64] appears to offer a reasonable explanation for the placental enlargement. Gouiard [83] noted a higher frequency of nuclear" ciated with a decreased thickness of the lntervillot~s space, and both lesions are major signs Indicating hypoxla~ Asmusseh [?9, 84] conduct- • ed electron microscopic studies on full-term human placentae and urn- • • bilical veins o| smoking and nonsmoking mothers. Ohty among the " • smokers did he find broadening of the basement mere. brahe of the pla- cental villus, increased collagen content Of tl~e villue~ decreased v~scuo larizatioa, and intim'al changes in the villous captllar!es and arterioles wlt.h pronounced inttmal edema. In th~ umbilical veins he.observed~pro- nounced edema in the subintimal space combined with a.destructton of Intimal ela~stlc membranes, "a inarked decrease in collagen content and a proliferative reaction of the monocyte~L Thus tobacco smoking causes T104231157

CIGARETTE SMOKING AND HUMAN PREGNANCIES 197 severe ds~,nage during pregnancy to the cord and the.pta~e~tal ~essels, and simitar changes might as well be expected to occur in the fetuses. In addition to possible changes tn fetal metabolism caused by ~ broad- ening of the b~sement membrane, the resulting decrease in vascular- izatton would provide an obvious reason for a.reduction in metabolism and diffusion across the placenta. These histopathologtc changes may help explain the fact that newborn children of heavy smokers are small It .must be pointed out, however, that other observations [22, 85, 86] have found no differences in placental size, micromorphology, and um- bilical cord histology [31]. Serum heat-stable alkaline phosphat~se (HSAP) concentration has been found.t.o be significantly ~hlgher in smokers than in nonsmokers [45]. Because HSAP is ex.ctusively synt.hestzed in the placenta, the authors suggested that toxic constituents of tobacco smoke might.pro- voke an increased production of HSAP. This m'ay occur as the resu|t of (1) active trophoblast proliferation, (2) damage to the cellula@ structure of the placenta with a consequent releaseof excess'HSAP "" into the maternal serum, or (3) a combination of the two factors. Juchau [~7] found that placentae obtained at term from smoking women had a greater ability to hydrokylate ben~zo(~)pyrene tha~. " . placentae from nonsmokers. Only very low hydroxylatlng activity was observed in placental tissue obtained ~rom smokers upon termina~ tion of'pregnancies during first trimester. Thus, duringthe first tri- mester, chemicals in tobacco smoke that are active as the parent com- pound might represent a greater hazard to the fetus of a smoking mother. In~ contrast, substances undergoing biotransformatfon to ac- tive metabolites might be more hazardous to the fetus.of the'smoking mother near term. .. Pertnatal Mortality Many investigators [2, 7, 12, 29, 34, .35, 38~ 47, 53,.71, 81] hav~ shown perinatal mortality risk to increase by nearly one-third in mothers who smoke regularly alter the fot/rth month of pregnancy independent of many environmental, socioeconomic, and maternal factors known to be associated with increased perihatal death rates. Pre.maturity anoxia and placental cbmpllcations are generally re- garded as being responsible for most of the increase. In a study of 50,000 births, Meyer et al. [34] found that peri~atal rhorta[ity in- creased 20 and 35% for <:1 pack/day and ~- 1 pack/day smokers, re" spectively, when adjusted for seven other factors, Naeye_ [38] found that perinatal mortality due to abruptio placentae wa~ 211~ more frequent in smokers than in nonsmokers in the first half Of gestation and 53% more frequent, a/ter mid-gestation. Other. investigators have no.ted a decrease or no change in the perinatal mortality'rate [56, a~]. In general, studies showing low mortality rates wlttm comparing lnlants of smoldng mothers to those of non- smokers and finding no signific,nt mortality differences also reveal Ti04231158

198 JOHNSTON the lowest proportio~ of low birth weight babies among nonsmokers [56, 89, 90]. Indeed, a very close association between low birthweight" and mortality seems to exist.. "in a British perlnatal mortality ~urvey it was found that ~a reduction of about 200 g in the usual birthweight of about 3500 g led to less than a tality risk, whereas the same r.eduction occurring in a 2500-g baby • resulted in about a 30% increase. Thus the greater the number of • • low birthwelght babies in a.populatlon, the greater, the increase in the mortality rate associated with the average decrease of about' 200 g attributable to smoking. ~rhls .association might provide apartiat ex- planation for the varying perinatal mortality ratios reported. Another possible explanation relates to the fact that some o.f the discrepant studtes involve low risk populations exhibited markedly decre~ed rates of low-birthweight babies and neonat~al mortality, wheh compared to other United States populations. Furthermore, the sample sizes in surveys finding no differences or even lower perinatal mortality ratios among babies born to smoking mothers are smalIbr than ln'thos~ studies which ~.eported higher mot-. tality ratios [1~,. 71]. Differences in population selection and methods of adjustment prior to statistical analysis to match smokers and non- smokers appears to contribute to the wide variations reported in pert- natal mortality .ratios. Th~ observations that significant differences in perinatal mortality rates are s.ttlt observed between smokers and non- smokers following many adjustments for confounding fac.tors, and that the enhanced risk of perinatal mortality can be eliminated if smoking is stepped during the first trimester of ~regnancy [7 I], strongly sup- port the contention that maternal.smoking raises the incidence of per-l- natal m.ortaltty. Postneonatal.Mortaltty: Morbidity and Behavior Several investigators have been "concerned about the potential ef- fects of smoking on neonatal and child development. In general, studies have. "revealed increased occurrence of infan.cy deaths," especially in the first year after birth [53, 88~ growth retardation of about 1.0 cm, and a retardation of reading ability by about 3-~t months at 7 and 11 years of age [91]..Furthermore, an ~ncreased frequency and duration of pedi- atric hospitalization and doctor visits [88] ~ increased frequency of respir'atory diseases [88, 92], and increased occurrence of infant sud- den death syndrome" [89, 93-95] h.ave been reported. In additio~, hyper- activity and "minimal cerebral dysfunction" [76, 96] compromised cog- nitive abilities on eight standardized.tests (including grade placement, " IQ, perceptual motor abilities, and linguistic, skills [~6] ) in infants born to smoking mothers Vs infants born to nonsmoking mothershave been observed. With one exception [97], .significant differences in newborns~ Apgar scores are not found [27, 85, 98]. In Dunn's [76] study, social class, which differed significantly between smokers and nonsmokers,. is controlled for.only in the analysts-of IQ scores. The height and read- T104231159