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Cigarette smoking and prematurity: a prospective study
OBSTETRICS
Cigarette smoking and prematurity: a prospective study TODD
M.
FRAZIER,
Sc.M.
GEORGE H. DAVIS, M.D. HYMAN GOLDSTEIN, PH.D. IRVING
D.
GOLDBERG,
M.P.H.
Baltimore, Maryland
I N 1 95 7, Simpson 1 reported in a retrospective study of 7,499 patients that the incidence of premature births was nearly twice as great for smoking mothers as it was for nonsmoking mothers. Later, in a similar study, Lowe~ demonstrated that the mean weight of infants of mothers who smoked regularly throughout pregnancy was 170 grams less than that of infants of mothers who never slIloked. Interest in these findings led to this prospt'ctive study with the objective of determining whether or not smoking is a significant determinant of prematurity (birth weigh t 2,500 grams or less). In addi tion to smoking hahits several other maternal factors were included for investigation. These were (1) work history dUl'ing the first tri-
mester of pregnancy; (2) education; (3) maternal blood group types, and (4) psychosomatic complaints. Method
Each year the staff of the Maternity Interviewing Service of the Baltimore City Health Department interviews approximately 6,500 pregnant women who are seeking prenatal care. The purpose of this interview is to determine their financial resources and immediate medical needs. On the basis of their ability to pay for care, these women arc either referred to private hospitals for prenatal care and delivery 01' are accepted for prenatal care in the clinics of the Baltimore City Health Department. Nearly all of the women who receive their prenatal care in health department clinics arc registered for delivery at the municipal hospital-the Baltimore City Hospital. Over 98 per cent of these women arc Negro. The patients included in this study con~ist of all Negro women seen at the Maternity Interviewing Service during 1959 who (1) were scheduled for delivery at the Baltimore City Hospital and (2) received
From the Baltimore City II ealth Department and the Biometrics Branch, National InJtitute of Neurological Diseases and Blindness. The current stud)' was supported by a grant from the Department of Health, Education and Welfare, United States Public Health Service, National Institutes of Health Research Grallt B-2154.
988
Volume 81 Number 5
Cigarette smoking and prematurity
prenatal care in prenatal clinics of the Baltimore City Health Department. This selection procedure provided an economically homogeneous group whose members had a similar prenatal and delivery experience. The information collccted in this study came from thrce sources. The first source was an intervicw which was conducted at thc Matcrnity Interviewing Service Clinic aftcr it had bcen dctermined that a woman met the study rcquircmcnts. This interview consisted of questions concerning smoking history, work history, cducation, and psychosomatic complaints. The questions used to devclop psychosomatic complaint scores werc those proposed by Stouffer and associates 3 as a part of a neuropsychiatric screening adjunct. Eight per cent of thc Womcn wcre intcrviewed during the first trimestcr of prcgnancy; 60 per ccnt during the sccond trimester, and 32 per cent during the third trimester. Thc sccond source was the prenatal clinic history from which maternal blood group typc and initial hemoglobin was obtained. All blood group typing was done at the samc laboratory. The third source, birth and stillbirth ccrtificates, provided thc following information: birth weight, sex, plurality, gravidity, mother's age, and the duration of pregnancy calculated from the datc of thc last mcnstrual pcriod. By using a cross-refercncc Table I. Dclivery status A. Pregnancy outcome for women who were included in study 2,828 Single live births 2,736 Pregnancies resulting in multiple births 52 Fetal deaths 31 Abortions 9 B. Withdrawn frolll study 87 Reregistered at other hospital 28 Not pregnant 22 Death before delivery 1 Moved frolll city 4 Delivered, birth certificate not found 12 Unknown delivery status 20 Total No. of women interviewed
989
system between birth and death certificates it was also possiblc to obtain a record of neonatal dcaths that occurred among the study population infants. In ordcr to determine the consistency of response to the interview a total of 197 patients werc reintcrviewed on arbitrarily selected days at the time of their visit to a prenatal clinic. The interval between first and second interviews ranged from 2 weeks to 6 months with a mcdian of 10 wceks. With difTcrcnt intcrviewers, questions on smoking history that led to a classification of smoker or nonsmoker showed 86 pcr cent agrecment; work history showed 89 per cent agreement; education showed 82 pCI' cent agrecment. For thc classification of psychosomatic scorcs used in this study the agreement was 85 pcr cent. Results
The cxtent to which the 2,915 women cnrolled in thc study were successfully followcd is shown in Tablc 1. Of thc women intcrviewed, 2,828, or 97 pCI' ccnt, wcre delivcred cithcr at thc Baltimorc City Hospital wherc they werc originally rcgistered for dclivcry, at othcr hospitals in thc city as emcrgcncy admissions, or cn routc to a hospital. The results of the study are bascd principally on the prcnatal information given by the 2,736 women who were delivered of single liveborn infants. A total of 87 womcn, :~ per cent of those interviewed, were withdrawn from thc study for the reasons shown in Tablc I. A transfer to another medical facility prior to delivery was causc for withdrawal from thc study sincc thcsc womcn no longcr met thc rcquirelllent of delivery scheduled at the Baltimore City Hospital. Smoking and prematurity
2,915
The study of smoking- history and prematurity has been limited to the 2,736 single live births in this series. A total of 92 pregnancies resulted in multi pic births, fetal deaths, or abortions. The smokers and nonsmokers with multiple births or abortions were distributcd in thc samc way as
Frazier et 01.
990
May, 1961
Am.
those who were delivered of single liveborn infants. The fetal dcaths will bc discussed latcr. A comparison of smoking history prior to prcgnancy and at the time of interview (Table II) shows consistency in smoking patterns. In this table a woman was classified as a "smoker" if she smoked every day. AIJ others, the nonsmoker and the occasional smoker, were classified as "nonsmoker." For the 1,563 women who were nonsmokers before pregnancy and at the time of interview the rate of prematurity was 11.2 per cent. A similar rate was observed for the 15-1- women who smoked before this pregnancy but who were nonsmokers at the time of interview. Only 59 women became cigarette smokers during pregnancy. For this group the prematurity rate was 13.6 per cent. Among women who smoked before pregnancy and at the time of interview, the rate of premature births was 18.6 per cent. Because of the consistency of
J. Oust.
& Gynec.
smoking history, smoking status at the time of interview was thc one analyzed. Table III shows the incidence of prematurity and mean birth weight for the 5 classifications of smoking history ranging from nonsmoker to women who smoked more than one pack per day. The incidence of prematurity increased with the amount smoked from a low of 11.1 per cent for the infants of nonsmokers to a high of 22.9 per cent for the infants of women who at the time of interview smoked more than a pack of cigarettes daily. Fig. 1 shows the relationship between the rate of prematurity and the amount smoked. The prematurity rate for nonsmokers and occasional smokers combined, hereafter called the "nonsmoker group," is 11.2 per cent compared to 18.4 per cent for the "smoking group." According to these figures, there is a 64 per cent excess in the rate of premature birth (that is, birth weight 2,500 grams or less) among the infants of Negro women who smoked
Table II. Number and per cent of premature infants according to mother's smoking history '1
Smoking history*
No. premature by birth weight (2,500 grams or less)
%
. lie/ore this IJrelinancy
I At time 0/ interview
Silllile live births
Nonsmoker Smok"r Nonsmoker Smoker
N ollSllIoker Nonsmoker Smoker Smoker
1,56:i 154 59 960
179
11.2 11.0 13.6 18.6
2,736
379
13.9
Total *Oc(~asiollal
premature
175 17 8
!
Table III. Prematurity rates and mean birth wei,ght according to alllollnt smoked Smoking histor), at time interview
0/
Nonsmoker Occasional smoker (not every day)
Births
Premature births*
1,547
172
170
(j"
premature
Iweight Mean birth I Standard del'i(grams) atioll (grams)
II. t
3,085
555
20
11.8
~,030
535
Less thall olle-half pack per day
5+9
92
16.8
~,952
575
One-half
one pack pel' day
~.')')
84
19.9
2,89+
545
More than one pack I)('r day
48
II
22.9
2,855
510
2,736
:n9
13.9
3,022
570
(0
Total *Birth weight 2,5()O grams or less.
Volume 81 Number 5
Cigarette smoking and prematurity
991
Table IV. Duration of pregnancy and mean birth weight for nonoperative deliveries according to smoking history Length of gestation in weeks
Mean birth weight (grams)
Number Smokers
Under 29 30-31 32-33 34-35 36-37 38-39 40-4·1 42-43 44 and over Unknown
22 32 31 77 151 270 202 54 27 14
Total known Mean
866 38.4
Nonsmokers
during pregnancy. Simpson's study showed a similar excess, 48 per cent, at the San Bernardino County Hospital, a hospital which presumably serves women from a similar economic level as the women who are delivered at the Baltimore City Hospital. The mean birth weight of infants of nonsmokers (including occasional smokers) in the present study was 3,080 grams compared to 2,924 grams for the infants of smokers. This statistically significant difference of 156 grams is in close agreement with the nonsmoker-smoker difference of 170 grams reported by Lowe. The mean duration of pregnancy ( excluding operative deliveries) for women who smoked was 38.4 weeks compared to 38.7 weeks for the nonsmokers (Table IV). The similarity of mean pregnancy duration of the two groups is an agreement with Lowe's finding for smokers and nonsmokers. For infants who were classed as premature by birth weight, the mean gestation was 35.1 weeks for the smoking mothers compared to 34.5 weeks for nonsmokers. Evidence that the infants of smokers weigh less than infants of nonsmokers for a wide range of pregnancy duration (Table IV, Fig. 2) suggests a fetal development mechanism rather than early onset of labor. For pregnancies of 34 weeks' duration or more, the mean weight of infants of nonsmokers was con-
I
Smokers
1,955 2,375 2,750 2,680 2,870 3,000 3,140 3,130 3,030
37 22 63 110 233 484 402 10O 40 7 1,491 38.7
Nonsmokers
2,195 2,475 2,545 2,905 2,990 3,125 3,250 3,360 3,265
3,080
2,924
sistently greater than the mean for infants of smokers. Lowe reports similar findings for pregnancies of 260 or more days' duration. For pregnancies of less than 34 weeks, the mean birth weights for infants of smokTable V. Characteristics of smokers and nonsmokers, similar frequencies* Smokers
Characteristic
No. studied 1,019
Nonsmokers
1,717
Age of mother 2 ( 0.2)t 296 (29.0) 349 (34.3) 226 (22.2) 100 ( 9.8) 46 ( 4.5)
Under 15 years 15-19 20-24 25-29 30-34 35 and over
14 504 585 332 169 113
( 0.8) (29.4 ) (34.1 ) (19.3 ) ( 9.8) ( 6.6)
lllood group type 249 (24.4) 188 (18.5) 471 (46.2) 47 ( 4.6) 64 ( 6.3)
A B 0 All Unknown
·l32 328 n07 64 86
(25.1 ) (19.1 ) (47.0) ( 3.7) ( 5.0)
Initial hemoglobin level (grams per 100 c.c.) 18 (1.8) Less than 8.7 43 ( 2.5) 592 (58.1) 8.7-11.5 1,007 (58.7) 314 (30.8) 11.6 or more 545 (31.7) Not df'terminpd 122 ( 7.1) 95 ( 9.3) Sex of child 481 (47.2) 538 (52.8)
867 (50.5) 850 (49.5)
Male Female
"Not significantly different (I' tPerccntagcs.
>
0.05).
992
May, 1961
Frazier et al.
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SOl C HIS TORY Fig. 1. Rate of prematurity according to smoking history (single live births, Negro, Baltimore).
ers and of nonsmokers were not significantly different. These results indicate an association between cigarette smoking and the rate of premature birth. It is possible, however, that this is a coincidence resulting from a third factor which is associated with both the frequency of premature birth and the amount of smoking. The possibility of such a relationship has been investigated for several factors. For the characteristics shown in Table V there is no evidence of a significant difference in distribution between smokers and nonsmokers. Thus, maternal age, blood group type, initial hemoglobin level, and sex of child are similar for smokers and nonsmokers. Table
"' E
2
f:I: ~
3500 3000 2500
4J
;t 2000
:I: f-
er iIi
1500
z
1000
« ::.
4J
500 0
2fE0:S
r-
30-31
J. Obst. & Gynec.
VI shows characteristics for which there are statistically significant differences between smokers and nonsmokers. Thus, for gravidity, work history, education, and psychosomatic complaint scores it is necessary to determine if the smoker-nonsmoker differences in prematurity rates exist for each level of the factors shown in this table . Gravidity
The rate of premature births among multigravidas who smoke is 18.5 per cent, a figure that is significantly greater than the 10 per cent for comparable nonsmokers (Table VII). The smoker-nonsmoker difference in the rate of prematurity for primigravidas is not statistically significant although the rate for smokers is higher. Mean birth weight in grams is also shown in Table VII. For the infants of multigravidas who smoke, the mean birth weight is significantly less, 194 grams, than the mean birth weight for infants of nonsmoking multigravidas. Work history
The rate of prematurity according to smoking and employment before or during the first trimester of this pregnancy is shown in Table VIII. For women who worked before this pregnancy there is a significant difference in the rate of prematurity between smokers (19.7 per cent) and nonsmokers (7.6 per cent). A somewhat smaller difference, but nevertheless a significant one, is obtained for women who were not working before this pregnancy. Similar results are obtained for work history during the first trimester. From these findings it follows that the smoker-nonsmoker difference in the rate of prematurity is independent of work history before or during the first trimester of pregnancy. Education
1
32 3; ;-;6:3 1 34~3')
t~-;~!
5B'~9
44
t
424~
DURATION OF PREGNANCY IN WEEKS
Fig. 2. Mean birth w('ight and duration of pregnancy (single live births, Negro, Baltimore).
Prematurity rates according to years of education and smoking history are shown in Table IX for three groups representing women whose education ended in elementary, junior high, or high school grades. Re-
Volume 81 Number 5
Cigarette smoking and prematurity
993
Table VI. Characteristics of smokers and nonsmokers, dissimilar frequencies* Smokers
Characteristic
Nonsmokers
No. studied 1,019
1,717
Gravidity 161 (15.8)t 858 (84.2)
Primigravida Multigravida
341 ( 19.9) 1,376 (80.1 )
Work history 335 (32.9) 684 (67.1) 356 (34.9) 663 (65.1)
Worked Did not Worked Did not
487 1,230 518 1,199
Education 111 (10.8) 518 (50.8) 390 (38.3)
Elementary school (1-6 years) Junior high school (7-9 years) High school or more (10 or more years)
before this pregnancy work before this pregnancy during first trimester work during first trimester
189 ( 11.0) 678 (39.5) 850 (49.5)
Psychosomatic complaint score 248 (24.3) "Nervous" (five or more complaints) 771 (75.7 ) "Normal" (less than five complaints) *Significant at p
<
(28.4) ( 71.6) (30.2) (69.8)
288 (16.8 ) 1,429 (83.2)
0.05.
t Percentages.
Table VII. Prematurity rates and mean birth weight according to gravidity and smoking history Gravidity Primig ravida
I
I
Smoking history
Births
Premature Per cent births premature
Nonsmoker Smoker
341 161
54 28
15.8 17.4
Tota l
502
82
16.3
1Mean birth weight
I
Multigravida
I
birth Premature Per cent IMean weight births premature (grams)
(grams)
Births
2,907 2,909
1,376 858
138 159
10.0 18.5
2,234
297
13.3
3,122 2,928
Table VIII. Prematurity rates according to work history and smoking habits Worked
Did not work
Premature SmokinlJ history
During first trimeJter Nonsmoker Smoker
Total
No.
%
155 121
12.6 17.7
276
14.4
1,199 663
148 113
12 .3 17 .0
1,862
261
14.0
%
No. births
37 66
7.6 19.7
1,23 0 684
822
103
12 .5
1,9 14
518 356
44 74
8.5 20.8
874
118
13.5
No. births
During month of last menses Nonsmoker 487 Smoker 335
Total
Premature
No.
--
--
994
Frazier et 01.
Am.
May, 1961 & Gynec.
J. Obst.
Table IX. Prematurity rates according to education and smoking history Years of education 6 )'ears or less
Smoking hiJtory
Births
Nonsmoker Smoker
189
III
Total
300
10 or more years
7 to 9 )'ears
I mature Pre- I prema-
I mature Pre- I prema%
%
births
ture
Births
18 21 39
9.5 18.9 13.0
678 518 1,196
gardless of the number of years of education reported, a significant difference was found between prematurity rates for smokers and for nonsmokers. Psychosomatic complaint scores
Investigations by Heath 4 and Lilienfeld 5 indicate that there are emotional differences between smokers and nonsmokers. For this reason, 15 questions developed by Stouffer and associates as a part of a neuropsychiatric scrC'ening adjunct were used as a part of the study interview. Responses to questions concerning health problems, trouble getting to sleep, trembling hands, fainting spells, nervousness, "heart beating hard," pressures or pains in the head, dizziness, fingernail bi ting, shortness of breath, sweating hands, sick headaches, upset stomach, nightmares, and "cold sweats" were used to divide the women in this study into two groups. Women who gave 5 01' more positive responses to these questions comprised a group for which the psychosomatic complaint score was high. For the purpose of this study these women have been labeled as "nervous." Women who reported fewer than 5 positive responses to the 15 questions, a low score, were called "normal." Table X shows the rate of prematurity for "nervous" and "nonnal" wornen according to their smoking history. In both the "normal" and "nervous" groups the rate of prematurity is significantly greater for the smokers; however, the "nervous" smokers have a significantly higher rate of prematurity (23 per cent) than the "normal" smokers (16.9 per cen t) .
births
ture
Births
Premature births
80 98 178
11.8 18.3 14.9
850 390 1,240
94 68 162
% I premature
11.1 17.4 13.1
Fetal and neonatal mortality
Fetal and neonatal death rates are higher for infants of cigarette smokers than for infants of nonsmokers. Table XI shows the number of deaths and the fetal and neonatal death rates for the two groups. The difference between the fetal death rate for the smoking group (15.5 per 1,000 births) and for the nonsmokers (6.4 per 1,000 births) is statistically significant. Although the neonatal death rate for infants of smokers (27.5 per 1,000 live births) is greater than the rate for the nonsmoker group (23.3 per 1,000 live births) the difT erence is not significant. In a review of previous pregnancies, the proportion of multigravidas who had at least one prior stillbirth was greater for smokers than for nonsmokers:lE- Of 858 multigravidas who were smokers, 79 or 9.2 per cent had a record of previous stillbirth. Among the 1,376 nonsmoking multigravidas, 99 or 7.2 per cent had had stillborn infants in previous pregnancies. These percentages by themselves are not significantly different; however, the previous stillbirth experience of the smokers appears to be consistent with their adverse experience in fetal and neonatal loss during the pregnancy followed in this study. Comment
This study of 2,736 pregnant Negro women who were interviewed prenatally and followed throughout pregnancy dem*It is not possihle at this time to determine the ac.tual prior stillbirth rate since the count of total previous pregnancies has not been processed.
Volume 81 Number 5
Cigarette smoking and prematurity 995
onstrates an association between cigarette smoking history and prematurity. Prematurity rates increased with the amount smoked from a low of 11.1 per cent for the nonsmoker (excluding occasional smokers) to a high of 22.9 per cent for women who at the time of interview smoked more than one pack per day. The smoker-nonsmoker difference in prematurity rates prevailed in the presence of several other factors which could possibly have caused a spurious association. Gravidity was an exception. For primigravidas, the smoker-nonsmoker difference in prematurity rates was not statistically significant whereas for the multigravidas it was. The lack of a significant difference among the primigravidas is perhaps related to the fact that in this group there are proportionately fewer heavy smokers than in the group of multigravidas. Among primigravidas only 31 per cent smoked more than one-half pack per day compared to 41 per cent of the multigravidas. It is also plausible that the effect of primig ravidity, which tends to increase the rate of prematurity, is greater than the association of prematurity with smoking per
se, thereby accounting for a diminished difference between nonsmokers and smokers. The similarity of the duration of pregnancy for smokers and for nonsmokers and the smaller mean birth weights for infants of smokers compared to those of nonsmokers, regardless of gestation after 32 weeks, suggests that a fetal development mechanism is involved rather than premature onset of labor. In appraising the results of this study two possibilities are suggested. The first, as pointed out by Yerushalmy,G is that "smoking acts as an index to differentiate smokers from nonsmokers on a number of different characteristics rather than as indicating a causal relationship." A second possibility is that smoking has a direct effect which leads to an increased rate of prematurity. For example, smoking might reduce maternal appetite to the extent that it would manifest itself in reduced weight of the newborn infant. Another possibility is that vasoconstriction caused by smoking might have an appreciable effect on fetal nutrition through a decrease in the blood supply reaching the intervillous space.
Table X. Prematurity rates according to psychosomatic complaint scores and smoking history Psychosomatic complaint score Low-normal
High - IIen'ollS
%
%
premature
Births
Premature birth.1
premature
SmokinJ: histor)'
Births
Premature births
Nonsmokers Smokers
1,429 771
162 130
11.3 16.9
288 248
30 57
10.4 23 .0
Tota l
2,200
292
13.3
5:~6
87
16.2
Table XI. Number and rate of fetal and neonatal deaths according to smoking history Number
Smoking history
Nonsmoker Smoker
No. live births
1,717 1,019
Fetal deaths II
16
D ea th rate
I Neonatal death s 40 28
Fetal death .l· pel' 1,000 rielil,eries
6.4 15.5
I Neonatal deaths per 1,000 live births
23.3 27.5
996
Frazier et 01.
From this study there was a reduced prematurity rate among the 154 women who elected to stop smoking during pregnancy. However, there is no evidence that q reduction in prematurity rates could be achieved in a randomly selected group by their curtailing or stopping cigarette smoking during pregnancy. Until the role of smoking and its association with increased prematurity is detelmined, each obstetrician must decide whether or not to advise his patients to limit smoking.
Summary
Cigarette smoking histories obtained from prenatal interviews with 2,736 Negro women who were delivered of single liveborn
Am.
J.
May, 1961 Obst. & Gynec.
infants show that the prematurity rate for smokers was 18.4 per cent compared to 11.2 per cent for nonsmokers (excluding occasional smokers). The rate of premature hirth increased with the amount smoked. This difference was independent of maternal age, blood group type, initial hemoglobin level, sex of child, work history, education, and psychosomatic complaint score. Although a difference in the prematurity rates for smokers and nonsmokers was found for the 2,234 multigravidas in this study it was not found to be significant for the 502 primigravidas. The evidence presented here is generally consistent with that of retrospective studies conducted in California by Simpson and in nirmingham, England, by Lowe.
REFERENCES
J.: A~I. J. OnsT. & GYNEC. 73: 808, 1957. 2. Lowe, C. R.: Brit. M. ]. 2: 673, 1959. 3. Stouffer, S. A., ct al.: Measurement and Prediction, Princeton, N. J., 1950, Princeton University Press, vol. 4, chap. 13. 4. Heath, C. W.: A. M. A. Arch. Int. Med. 101: 377, 1958. 1. Simpson, W.
5. Lilienfeld, A. M.: J. Nat. Cancer Inst. 22: 259, 1959. 6. Yerushalmy, .J.: Statistical Considerations and Evaluation of Epidemiologic Evidence, a paper presented before the symposium on tobacco and health at the New York Academy of Medicine, Sept. 26, 1960.
Cigarette smoking and prematurity: a prospective study TODD
M.
FRAZIER,
Sc.M.
GEORGE H. DAVIS, M.D. HYMAN GOLDSTEIN, PH.D. IRVING
D.
GOLDBERG,
M.P.H.
Baltimore, Maryland
I N 1 95 7, Simpson 1 reported in a retrospective study of 7,499 patients that the incidence of premature births was nearly twice as great for smoking mothers as it was for nonsmoking mothers. Later, in a similar study, Lowe~ demonstrated that the mean weight of infants of mothers who smoked regularly throughout pregnancy was 170 grams less than that of infants of mothers who never slIloked. Interest in these findings led to this prospt'ctive study with the objective of determining whether or not smoking is a significant determinant of prematurity (birth weigh t 2,500 grams or less). In addi tion to smoking hahits several other maternal factors were included for investigation. These were (1) work history dUl'ing the first tri-
mester of pregnancy; (2) education; (3) maternal blood group types, and (4) psychosomatic complaints. Method
Each year the staff of the Maternity Interviewing Service of the Baltimore City Health Department interviews approximately 6,500 pregnant women who are seeking prenatal care. The purpose of this interview is to determine their financial resources and immediate medical needs. On the basis of their ability to pay for care, these women arc either referred to private hospitals for prenatal care and delivery 01' are accepted for prenatal care in the clinics of the Baltimore City Health Department. Nearly all of the women who receive their prenatal care in health department clinics arc registered for delivery at the municipal hospital-the Baltimore City Hospital. Over 98 per cent of these women arc Negro. The patients included in this study con~ist of all Negro women seen at the Maternity Interviewing Service during 1959 who (1) were scheduled for delivery at the Baltimore City Hospital and (2) received
From the Baltimore City II ealth Department and the Biometrics Branch, National InJtitute of Neurological Diseases and Blindness. The current stud)' was supported by a grant from the Department of Health, Education and Welfare, United States Public Health Service, National Institutes of Health Research Grallt B-2154.
988
Volume 81 Number 5
Cigarette smoking and prematurity
prenatal care in prenatal clinics of the Baltimore City Health Department. This selection procedure provided an economically homogeneous group whose members had a similar prenatal and delivery experience. The information collccted in this study came from thrce sources. The first source was an intervicw which was conducted at thc Matcrnity Interviewing Service Clinic aftcr it had bcen dctermined that a woman met the study rcquircmcnts. This interview consisted of questions concerning smoking history, work history, cducation, and psychosomatic complaints. The questions used to devclop psychosomatic complaint scores werc those proposed by Stouffer and associates 3 as a part of a neuropsychiatric screening adjunct. Eight per cent of thc Womcn wcre intcrviewed during the first trimestcr of prcgnancy; 60 per ccnt during the sccond trimester, and 32 per cent during the third trimester. Thc sccond source was the prenatal clinic history from which maternal blood group typc and initial hemoglobin was obtained. All blood group typing was done at the samc laboratory. The third source, birth and stillbirth ccrtificates, provided thc following information: birth weight, sex, plurality, gravidity, mother's age, and the duration of pregnancy calculated from the datc of thc last mcnstrual pcriod. By using a cross-refercncc Table I. Dclivery status A. Pregnancy outcome for women who were included in study 2,828 Single live births 2,736 Pregnancies resulting in multiple births 52 Fetal deaths 31 Abortions 9 B. Withdrawn frolll study 87 Reregistered at other hospital 28 Not pregnant 22 Death before delivery 1 Moved frolll city 4 Delivered, birth certificate not found 12 Unknown delivery status 20 Total No. of women interviewed
989
system between birth and death certificates it was also possiblc to obtain a record of neonatal dcaths that occurred among the study population infants. In ordcr to determine the consistency of response to the interview a total of 197 patients werc reintcrviewed on arbitrarily selected days at the time of their visit to a prenatal clinic. The interval between first and second interviews ranged from 2 weeks to 6 months with a mcdian of 10 wceks. With difTcrcnt intcrviewers, questions on smoking history that led to a classification of smoker or nonsmoker showed 86 pcr cent agrecment; work history showed 89 per cent agreement; education showed 82 pCI' cent agrecment. For thc classification of psychosomatic scorcs used in this study the agreement was 85 pcr cent. Results
The cxtent to which the 2,915 women cnrolled in thc study were successfully followcd is shown in Tablc 1. Of thc women intcrviewed, 2,828, or 97 pCI' ccnt, wcre delivcred cithcr at thc Baltimorc City Hospital wherc they werc originally rcgistered for dclivcry, at othcr hospitals in thc city as emcrgcncy admissions, or cn routc to a hospital. The results of the study are bascd principally on the prcnatal information given by the 2,736 women who were delivered of single liveborn infants. A total of 87 womcn, :~ per cent of those interviewed, were withdrawn from thc study for the reasons shown in Tablc I. A transfer to another medical facility prior to delivery was causc for withdrawal from thc study sincc thcsc womcn no longcr met thc rcquirelllent of delivery scheduled at the Baltimore City Hospital. Smoking and prematurity
2,915
The study of smoking- history and prematurity has been limited to the 2,736 single live births in this series. A total of 92 pregnancies resulted in multi pic births, fetal deaths, or abortions. The smokers and nonsmokers with multiple births or abortions were distributcd in thc samc way as
Frazier et 01.
990
May, 1961
Am.
those who were delivered of single liveborn infants. The fetal dcaths will bc discussed latcr. A comparison of smoking history prior to prcgnancy and at the time of interview (Table II) shows consistency in smoking patterns. In this table a woman was classified as a "smoker" if she smoked every day. AIJ others, the nonsmoker and the occasional smoker, were classified as "nonsmoker." For the 1,563 women who were nonsmokers before pregnancy and at the time of interview the rate of prematurity was 11.2 per cent. A similar rate was observed for the 15-1- women who smoked before this pregnancy but who were nonsmokers at the time of interview. Only 59 women became cigarette smokers during pregnancy. For this group the prematurity rate was 13.6 per cent. Among women who smoked before pregnancy and at the time of interview, the rate of premature births was 18.6 per cent. Because of the consistency of
J. Oust.
& Gynec.
smoking history, smoking status at the time of interview was thc one analyzed. Table III shows the incidence of prematurity and mean birth weight for the 5 classifications of smoking history ranging from nonsmoker to women who smoked more than one pack per day. The incidence of prematurity increased with the amount smoked from a low of 11.1 per cent for the infants of nonsmokers to a high of 22.9 per cent for the infants of women who at the time of interview smoked more than a pack of cigarettes daily. Fig. 1 shows the relationship between the rate of prematurity and the amount smoked. The prematurity rate for nonsmokers and occasional smokers combined, hereafter called the "nonsmoker group," is 11.2 per cent compared to 18.4 per cent for the "smoking group." According to these figures, there is a 64 per cent excess in the rate of premature birth (that is, birth weight 2,500 grams or less) among the infants of Negro women who smoked
Table II. Number and per cent of premature infants according to mother's smoking history '1
Smoking history*
No. premature by birth weight (2,500 grams or less)
%
. lie/ore this IJrelinancy
I At time 0/ interview
Silllile live births
Nonsmoker Smok"r Nonsmoker Smoker
N ollSllIoker Nonsmoker Smoker Smoker
1,56:i 154 59 960
179
11.2 11.0 13.6 18.6
2,736
379
13.9
Total *Oc(~asiollal
premature
175 17 8
!
Table III. Prematurity rates and mean birth wei,ght according to alllollnt smoked Smoking histor), at time interview
0/
Nonsmoker Occasional smoker (not every day)
Births
Premature births*
1,547
172
170
(j"
premature
Iweight Mean birth I Standard del'i(grams) atioll (grams)
II. t
3,085
555
20
11.8
~,030
535
Less thall olle-half pack per day
5+9
92
16.8
~,952
575
One-half
one pack pel' day
~.')')
84
19.9
2,89+
545
More than one pack I)('r day
48
II
22.9
2,855
510
2,736
:n9
13.9
3,022
570
(0
Total *Birth weight 2,5()O grams or less.
Volume 81 Number 5
Cigarette smoking and prematurity
991
Table IV. Duration of pregnancy and mean birth weight for nonoperative deliveries according to smoking history Length of gestation in weeks
Mean birth weight (grams)
Number Smokers
Under 29 30-31 32-33 34-35 36-37 38-39 40-4·1 42-43 44 and over Unknown
22 32 31 77 151 270 202 54 27 14
Total known Mean
866 38.4
Nonsmokers
during pregnancy. Simpson's study showed a similar excess, 48 per cent, at the San Bernardino County Hospital, a hospital which presumably serves women from a similar economic level as the women who are delivered at the Baltimore City Hospital. The mean birth weight of infants of nonsmokers (including occasional smokers) in the present study was 3,080 grams compared to 2,924 grams for the infants of smokers. This statistically significant difference of 156 grams is in close agreement with the nonsmoker-smoker difference of 170 grams reported by Lowe. The mean duration of pregnancy ( excluding operative deliveries) for women who smoked was 38.4 weeks compared to 38.7 weeks for the nonsmokers (Table IV). The similarity of mean pregnancy duration of the two groups is an agreement with Lowe's finding for smokers and nonsmokers. For infants who were classed as premature by birth weight, the mean gestation was 35.1 weeks for the smoking mothers compared to 34.5 weeks for nonsmokers. Evidence that the infants of smokers weigh less than infants of nonsmokers for a wide range of pregnancy duration (Table IV, Fig. 2) suggests a fetal development mechanism rather than early onset of labor. For pregnancies of 34 weeks' duration or more, the mean weight of infants of nonsmokers was con-
I
Smokers
1,955 2,375 2,750 2,680 2,870 3,000 3,140 3,130 3,030
37 22 63 110 233 484 402 10O 40 7 1,491 38.7
Nonsmokers
2,195 2,475 2,545 2,905 2,990 3,125 3,250 3,360 3,265
3,080
2,924
sistently greater than the mean for infants of smokers. Lowe reports similar findings for pregnancies of 260 or more days' duration. For pregnancies of less than 34 weeks, the mean birth weights for infants of smokTable V. Characteristics of smokers and nonsmokers, similar frequencies* Smokers
Characteristic
No. studied 1,019
Nonsmokers
1,717
Age of mother 2 ( 0.2)t 296 (29.0) 349 (34.3) 226 (22.2) 100 ( 9.8) 46 ( 4.5)
Under 15 years 15-19 20-24 25-29 30-34 35 and over
14 504 585 332 169 113
( 0.8) (29.4 ) (34.1 ) (19.3 ) ( 9.8) ( 6.6)
lllood group type 249 (24.4) 188 (18.5) 471 (46.2) 47 ( 4.6) 64 ( 6.3)
A B 0 All Unknown
·l32 328 n07 64 86
(25.1 ) (19.1 ) (47.0) ( 3.7) ( 5.0)
Initial hemoglobin level (grams per 100 c.c.) 18 (1.8) Less than 8.7 43 ( 2.5) 592 (58.1) 8.7-11.5 1,007 (58.7) 314 (30.8) 11.6 or more 545 (31.7) Not df'terminpd 122 ( 7.1) 95 ( 9.3) Sex of child 481 (47.2) 538 (52.8)
867 (50.5) 850 (49.5)
Male Female
"Not significantly different (I' tPerccntagcs.
>
0.05).
992
May, 1961
Frazier et al.
-: ... =_
2
o
20 8 :6 •
8D
Am.
2
.. I-
2
8 I6
-
-
r
r-
-
-
.
2
0
I-
tS
,n
Al
S fI
c
~-I
I
'AC It
I
c
~I
.,
, C '[1
,(1
If
SOl C HIS TORY Fig. 1. Rate of prematurity according to smoking history (single live births, Negro, Baltimore).
ers and of nonsmokers were not significantly different. These results indicate an association between cigarette smoking and the rate of premature birth. It is possible, however, that this is a coincidence resulting from a third factor which is associated with both the frequency of premature birth and the amount of smoking. The possibility of such a relationship has been investigated for several factors. For the characteristics shown in Table V there is no evidence of a significant difference in distribution between smokers and nonsmokers. Thus, maternal age, blood group type, initial hemoglobin level, and sex of child are similar for smokers and nonsmokers. Table
"' E
2
f:I: ~
3500 3000 2500
4J
;t 2000
:I: f-
er iIi
1500
z
1000
« ::.
4J
500 0
2fE0:S
r-
30-31
J. Obst. & Gynec.
VI shows characteristics for which there are statistically significant differences between smokers and nonsmokers. Thus, for gravidity, work history, education, and psychosomatic complaint scores it is necessary to determine if the smoker-nonsmoker differences in prematurity rates exist for each level of the factors shown in this table . Gravidity
The rate of premature births among multigravidas who smoke is 18.5 per cent, a figure that is significantly greater than the 10 per cent for comparable nonsmokers (Table VII). The smoker-nonsmoker difference in the rate of prematurity for primigravidas is not statistically significant although the rate for smokers is higher. Mean birth weight in grams is also shown in Table VII. For the infants of multigravidas who smoke, the mean birth weight is significantly less, 194 grams, than the mean birth weight for infants of nonsmoking multigravidas. Work history
The rate of prematurity according to smoking and employment before or during the first trimester of this pregnancy is shown in Table VIII. For women who worked before this pregnancy there is a significant difference in the rate of prematurity between smokers (19.7 per cent) and nonsmokers (7.6 per cent). A somewhat smaller difference, but nevertheless a significant one, is obtained for women who were not working before this pregnancy. Similar results are obtained for work history during the first trimester. From these findings it follows that the smoker-nonsmoker difference in the rate of prematurity is independent of work history before or during the first trimester of pregnancy. Education
1
32 3; ;-;6:3 1 34~3')
t~-;~!
5B'~9
44
t
424~
DURATION OF PREGNANCY IN WEEKS
Fig. 2. Mean birth w('ight and duration of pregnancy (single live births, Negro, Baltimore).
Prematurity rates according to years of education and smoking history are shown in Table IX for three groups representing women whose education ended in elementary, junior high, or high school grades. Re-
Volume 81 Number 5
Cigarette smoking and prematurity
993
Table VI. Characteristics of smokers and nonsmokers, dissimilar frequencies* Smokers
Characteristic
Nonsmokers
No. studied 1,019
1,717
Gravidity 161 (15.8)t 858 (84.2)
Primigravida Multigravida
341 ( 19.9) 1,376 (80.1 )
Work history 335 (32.9) 684 (67.1) 356 (34.9) 663 (65.1)
Worked Did not Worked Did not
487 1,230 518 1,199
Education 111 (10.8) 518 (50.8) 390 (38.3)
Elementary school (1-6 years) Junior high school (7-9 years) High school or more (10 or more years)
before this pregnancy work before this pregnancy during first trimester work during first trimester
189 ( 11.0) 678 (39.5) 850 (49.5)
Psychosomatic complaint score 248 (24.3) "Nervous" (five or more complaints) 771 (75.7 ) "Normal" (less than five complaints) *Significant at p
<
(28.4) ( 71.6) (30.2) (69.8)
288 (16.8 ) 1,429 (83.2)
0.05.
t Percentages.
Table VII. Prematurity rates and mean birth weight according to gravidity and smoking history Gravidity Primig ravida
I
I
Smoking history
Births
Premature Per cent births premature
Nonsmoker Smoker
341 161
54 28
15.8 17.4
Tota l
502
82
16.3
1Mean birth weight
I
Multigravida
I
birth Premature Per cent IMean weight births premature (grams)
(grams)
Births
2,907 2,909
1,376 858
138 159
10.0 18.5
2,234
297
13.3
3,122 2,928
Table VIII. Prematurity rates according to work history and smoking habits Worked
Did not work
Premature SmokinlJ history
During first trimeJter Nonsmoker Smoker
Total
No.
%
155 121
12.6 17.7
276
14.4
1,199 663
148 113
12 .3 17 .0
1,862
261
14.0
%
No. births
37 66
7.6 19.7
1,23 0 684
822
103
12 .5
1,9 14
518 356
44 74
8.5 20.8
874
118
13.5
No. births
During month of last menses Nonsmoker 487 Smoker 335
Total
Premature
No.
--
--
994
Frazier et 01.
Am.
May, 1961 & Gynec.
J. Obst.
Table IX. Prematurity rates according to education and smoking history Years of education 6 )'ears or less
Smoking hiJtory
Births
Nonsmoker Smoker
189
III
Total
300
10 or more years
7 to 9 )'ears
I mature Pre- I prema-
I mature Pre- I prema%
%
births
ture
Births
18 21 39
9.5 18.9 13.0
678 518 1,196
gardless of the number of years of education reported, a significant difference was found between prematurity rates for smokers and for nonsmokers. Psychosomatic complaint scores
Investigations by Heath 4 and Lilienfeld 5 indicate that there are emotional differences between smokers and nonsmokers. For this reason, 15 questions developed by Stouffer and associates as a part of a neuropsychiatric scrC'ening adjunct were used as a part of the study interview. Responses to questions concerning health problems, trouble getting to sleep, trembling hands, fainting spells, nervousness, "heart beating hard," pressures or pains in the head, dizziness, fingernail bi ting, shortness of breath, sweating hands, sick headaches, upset stomach, nightmares, and "cold sweats" were used to divide the women in this study into two groups. Women who gave 5 01' more positive responses to these questions comprised a group for which the psychosomatic complaint score was high. For the purpose of this study these women have been labeled as "nervous." Women who reported fewer than 5 positive responses to the 15 questions, a low score, were called "normal." Table X shows the rate of prematurity for "nervous" and "nonnal" wornen according to their smoking history. In both the "normal" and "nervous" groups the rate of prematurity is significantly greater for the smokers; however, the "nervous" smokers have a significantly higher rate of prematurity (23 per cent) than the "normal" smokers (16.9 per cen t) .
births
ture
Births
Premature births
80 98 178
11.8 18.3 14.9
850 390 1,240
94 68 162
% I premature
11.1 17.4 13.1
Fetal and neonatal mortality
Fetal and neonatal death rates are higher for infants of cigarette smokers than for infants of nonsmokers. Table XI shows the number of deaths and the fetal and neonatal death rates for the two groups. The difference between the fetal death rate for the smoking group (15.5 per 1,000 births) and for the nonsmokers (6.4 per 1,000 births) is statistically significant. Although the neonatal death rate for infants of smokers (27.5 per 1,000 live births) is greater than the rate for the nonsmoker group (23.3 per 1,000 live births) the difT erence is not significant. In a review of previous pregnancies, the proportion of multigravidas who had at least one prior stillbirth was greater for smokers than for nonsmokers:lE- Of 858 multigravidas who were smokers, 79 or 9.2 per cent had a record of previous stillbirth. Among the 1,376 nonsmoking multigravidas, 99 or 7.2 per cent had had stillborn infants in previous pregnancies. These percentages by themselves are not significantly different; however, the previous stillbirth experience of the smokers appears to be consistent with their adverse experience in fetal and neonatal loss during the pregnancy followed in this study. Comment
This study of 2,736 pregnant Negro women who were interviewed prenatally and followed throughout pregnancy dem*It is not possihle at this time to determine the ac.tual prior stillbirth rate since the count of total previous pregnancies has not been processed.
Volume 81 Number 5
Cigarette smoking and prematurity 995
onstrates an association between cigarette smoking history and prematurity. Prematurity rates increased with the amount smoked from a low of 11.1 per cent for the nonsmoker (excluding occasional smokers) to a high of 22.9 per cent for women who at the time of interview smoked more than one pack per day. The smoker-nonsmoker difference in prematurity rates prevailed in the presence of several other factors which could possibly have caused a spurious association. Gravidity was an exception. For primigravidas, the smoker-nonsmoker difference in prematurity rates was not statistically significant whereas for the multigravidas it was. The lack of a significant difference among the primigravidas is perhaps related to the fact that in this group there are proportionately fewer heavy smokers than in the group of multigravidas. Among primigravidas only 31 per cent smoked more than one-half pack per day compared to 41 per cent of the multigravidas. It is also plausible that the effect of primig ravidity, which tends to increase the rate of prematurity, is greater than the association of prematurity with smoking per
se, thereby accounting for a diminished difference between nonsmokers and smokers. The similarity of the duration of pregnancy for smokers and for nonsmokers and the smaller mean birth weights for infants of smokers compared to those of nonsmokers, regardless of gestation after 32 weeks, suggests that a fetal development mechanism is involved rather than premature onset of labor. In appraising the results of this study two possibilities are suggested. The first, as pointed out by Yerushalmy,G is that "smoking acts as an index to differentiate smokers from nonsmokers on a number of different characteristics rather than as indicating a causal relationship." A second possibility is that smoking has a direct effect which leads to an increased rate of prematurity. For example, smoking might reduce maternal appetite to the extent that it would manifest itself in reduced weight of the newborn infant. Another possibility is that vasoconstriction caused by smoking might have an appreciable effect on fetal nutrition through a decrease in the blood supply reaching the intervillous space.
Table X. Prematurity rates according to psychosomatic complaint scores and smoking history Psychosomatic complaint score Low-normal
High - IIen'ollS
%
%
premature
Births
Premature birth.1
premature
SmokinJ: histor)'
Births
Premature births
Nonsmokers Smokers
1,429 771
162 130
11.3 16.9
288 248
30 57
10.4 23 .0
Tota l
2,200
292
13.3
5:~6
87
16.2
Table XI. Number and rate of fetal and neonatal deaths according to smoking history Number
Smoking history
Nonsmoker Smoker
No. live births
1,717 1,019
Fetal deaths II
16
D ea th rate
I Neonatal death s 40 28
Fetal death .l· pel' 1,000 rielil,eries
6.4 15.5
I Neonatal deaths per 1,000 live births
23.3 27.5
996
Frazier et 01.
From this study there was a reduced prematurity rate among the 154 women who elected to stop smoking during pregnancy. However, there is no evidence that q reduction in prematurity rates could be achieved in a randomly selected group by their curtailing or stopping cigarette smoking during pregnancy. Until the role of smoking and its association with increased prematurity is detelmined, each obstetrician must decide whether or not to advise his patients to limit smoking.
Summary
Cigarette smoking histories obtained from prenatal interviews with 2,736 Negro women who were delivered of single liveborn
Am.
J.
May, 1961 Obst. & Gynec.
infants show that the prematurity rate for smokers was 18.4 per cent compared to 11.2 per cent for nonsmokers (excluding occasional smokers). The rate of premature hirth increased with the amount smoked. This difference was independent of maternal age, blood group type, initial hemoglobin level, sex of child, work history, education, and psychosomatic complaint score. Although a difference in the prematurity rates for smokers and nonsmokers was found for the 2,234 multigravidas in this study it was not found to be significant for the 502 primigravidas. The evidence presented here is generally consistent with that of retrospective studies conducted in California by Simpson and in nirmingham, England, by Lowe.
REFERENCES
J.: A~I. J. OnsT. & GYNEC. 73: 808, 1957. 2. Lowe, C. R.: Brit. M. ]. 2: 673, 1959. 3. Stouffer, S. A., ct al.: Measurement and Prediction, Princeton, N. J., 1950, Princeton University Press, vol. 4, chap. 13. 4. Heath, C. W.: A. M. A. Arch. Int. Med. 101: 377, 1958. 1. Simpson, W.
5. Lilienfeld, A. M.: J. Nat. Cancer Inst. 22: 259, 1959. 6. Yerushalmy, .J.: Statistical Considerations and Evaluation of Epidemiologic Evidence, a paper presented before the symposium on tobacco and health at the New York Academy of Medicine, Sept. 26, 1960.