Late Fetal and Neonatal Deaths

Considerable variation has occurred in the definition of the study
population among the studies in which the relationship of cigarette
smoking to fetal mortality (other than abortion) and early infant
mortality was examined. The most commonly identified study popula.
tions have been perinatal deaths, neonatal deaths, and late fetal plus
neonatal deaths, Perinatal deaths are a combination of late fetal deaths
(Le., stillborn infants) and deaths occurring within the first week of
life. Neonatal deaths include all deaths of liveborn infants within the
first 28 days of life.

EPIDEMIOLOGICAL STUDIES

Most of the earlier epidemiological studies of the association between
cigarette smoking and late fetal plus neonatal mortality were reviewed
in the 1971 and 1972 reports on the health consequences of smoking
(101, 102). A review of previously unreported studies (67, 76), as well
as reexamination of previously cited studies, forms the basis of the
following statements:

The results of several prospective and retrospective studies indicate
a statistically significant higher late fetal and/or neonatal mortality
for the infants of smokers compared to those of nonsmokers (14,17,
45, 43). The results of other prospective and retrospective studies iden-
tified no significant difference in the mortality rates between the in-
fants of smokers and nonsmokers (20, 65. 72. 85, 100, 115).

If mortality rates were compared for those infants of smokers and
nonsmokers weighing less than 2.500 grams. the infants of nonsmokers
apparently had a considerably higher risk than did those of smokers.

The results of recent studies, coupled with a critical review of the
design and analysis of previous studies, and a reexamination of exist-
ing data, may provide at least a partial explanation of discrepancies
between the results of previous studies.

Comparisons of the Mortality Risks of Low-Birth-Weight Infants
Born to Smokers and Nonsmokers

The perinatal mortality risk for infants weighing less than 2.500
grams appears to be lower for those infants born to women who
smoke during pregnancy than for those born to nonsmokers (table

126
3). However, available evidence shows that cigarette smokers’ infants
tend to be small-for-gestational age rather than gestationally pre-
mature, Hence, within a given birth weight group, the infants of
smokers are, on the average, gestationally more mature than those of
nonsmokers. Data collected by the National Center for Health Sta-
tistics (703) demonstrate that within a given birth weight group, the
more gestationally mature an infant, the lower is its mortality risk
(fig. 6). Thus, the difference in perinatal mortality risks experienced
hy the infants of cigarette smokers and nonsmokers, within comparable
birth weight classes, reflects the facts that the two sets of infants are
not of the same average gestational age, and that gestational age is
a major factor influencing late fetal and neonatal mortality. An accu-
rate estimate of comparative mortality risks for the infants of cig-
arette smokers and nonsmokers requires adjustment for gestational
age,

For infants of comparable gestational age, lower birth weight is as-
sociated with higher mortality (fig. 6). Since infants of cigarette
smokers have, on the average, lower birth weights than the infants of
nonsmokers, within groups of comparable gestational age, cigarette
smokers’ infants should experience higher mortality rates than non-
smokers’ infants of similar gestational ages. In a recent review, Meyer
and Comstock (51) provided a more extensixe discussion of these
points,

TABLE 3.—Comparison of the perinatal mortality for infants weighing
less than 2,500 grams, of smokers and nonsmokers

 

 

 

Perinatal mortality rate (deaths per 1,000
live births)
Authcr, reference me
Smokers Nonsmokers
Underwood, et al. (100)............ 187 269
Ontario Department of Health (67)_22 2 232 300
Kullander and Kallen (43)... 129 139
Rantakallio (76)... 288 344
erushalmy ! (112):

Black women_._-___--._-.-..-8 114 202
White women__.__..... 114 218

Butler and Alberman (14)._............ 269 284

 

' Reported neonatal mortality rates only.

127
Figure 6.—Neonatal mortality rates among single white births in hospitals by
detailed birth weight and specified gestation groups: United States),

JANUARY 1 TO MARCH 31, 1950

 

 

   
      

 

 

 

 

 

 

 

 

 

 

 

 

 

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£ 100 * \
£ 80 *, 32-35 \
a + weeks
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a * 37 weeks and over
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ow in on no Of HO o8
on oN on AH YN RO ow
aoe HN NN NN NN NM oon

BIRTH WEIGHT (in grams)

SOURCE: U.S. Public Heaith Service, National Center for Health Statistics (103).

Recent Studies

The Ontario Perinatal Mortality Study (66, 67) was conducted
among 10 teaching hospitals during 1960 and 1961. In this retrospee-
tive study of 51.490 pregnancies, a statistically significant increase
in the perinatal mortality rate was demonstrated for smokers’ in-
fants as compared with those of nonsmokers; the infants of smokers
experienced an overall relative risk of 1.27 (P<0.001). Moreover, the
investigators found a statistically significant dose-response relationship
between the amount of cigarettes smoked and the perinatal mortality
rate (P<0.001) (fig. 7).

128
Figure 7.—Perinatal mortality rate per 1,000 total births by cigarette smoking

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

category.
2
t 40 F
2a
‘s
3 33.4
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8 307 27.7 ZZ
5 23.2 CL)
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8 oy L CL) CA)
2 Ld CO)
§ CL CL)
°
E CZ) CL)
5 10+ Z 4 ZA
a
£
0 LZ Zo
Nonsmoker <1 pack of 21 pack of
cigarettes cigarettes
per day per day
Number of
perinatal deaths: 659 425 220
Total births: 28,358 15,328 6,581
(P <0.001)

SOURCE: Ontario Department of Health (66).

Recently Butler, et al. (75) further analyzed the British Perinatal
Mortality Study. They found a highly significant association between
maternal smoking after the fourth month of pregnancy and both
late fetal and neonatal deaths. Infants of smokers had an increase in
the late fetal mortality rate of 30 percent, and an increase in the neo-
natal mortality rate of 26 percent, compared to the infants of non-
‘mokers. The overall mortality ratio of late fetal plus neonatal deaths
Vas 1.28 (P< 0.001). Given the large number of women in the study,
‘nd the significant changes in smoking behavior which occurred,
they found it possible to consider the effect of a change in smoking

129
behavior between the beginning of pregnancy and the fourth month
on late fetal and neonatal mortality. A statistically significant and
dose-related increase in mortality occurred among the infants ot
mothers who continued to smoke after the fourth month of pregnancy,
as compared with the infants of nonsmokers and those of women who
smoked prior to the pregnancy but gave up smoking by the fourt),
month of gestation.

Niswander and Gordon (63) reported data from the prospective
Collaborative Perinatal Study of the National Institute of Neurologi.
cal Disease and Stroke. The 39,215 pregnancies registered at 12 unj.
versity hospitals in the United States were almost equally divided
between black and white women. They found a nonsignificant INCrease
in perinatal mortality among the infants of white smokers as compared
to those of white nonsmokers; the overall mortality ratio was 1.13
(P>0.1). The infants of black smokers, however, had a significantly
higher mortality risk than did those of black nonsmokers; the mor-
tality ratio was 1.18 (P<0.02). Moreover, a definite dose-response re.
lationship between cigarettes smoked by pregnant mothers anq
mortality risk was shown for black infants. Black women were noted to
smoke significantly fewer cigarettes, on the average, than white
women.

Rush and Kass (82) found, in a prospective study of 3.276 preg-
nancies followed at Boston City Hospital, a nonsignificant increase
in late fetal plus neonatal mortality rate among the infants of white
women who smoked as compared to those of white nonsmokers, How-
ever, the infants of black women who smoked had a statistically sig-
nificant increase in mortality rate compared to the infants of black
nonsmokers (P<0.01). The overall] mortality ratio for black women
who smoked was 1.86. The difference in frequency of stillbirth among
the infants of smokers and nonsmokers was the primary factor which
contributed to the significance of the difference in mortality rates,

Analysis of Previously Reported Studies

Previously reported studies can be divided into two groups: A group
in which the late fetal plus neonatal mortality rates for infants born
to cigarette smokers were significantly higher than those for the
infants born to nonsmokers, and a group in which no significant
differences were detected in the mortality rates for the infants born
to smokers and nonsmokers. The results of several studies (74. 17, 25.
42, 43, 55, 84, 92) yielded mortality ratios ranging from 1.38 to 1.78
The results of other studies (20, 65. 76. 85, 100, 115) yielded mortality
ratios ranging from 1.01 to 1.06, Both groups contained retrospective
and prospective studies of comparable size. The two groups did differ

130
significantly, however, with regard to control of variables other than
vigarette smoking which influence perinatal mortality.

Factors Which Influence Perinatal Mortality Other Than Smoking

Butler and Alberman (73), on data from the British Perinatal
Mortality Study, employed a logit transformation analysis of variance,
and demonstrated that maternal height, age, parity, social class, and
~vere preeclampsia all had a significant independent effect on late
fetal and neonatal mortality. Rumeau-Roquette (87) provided evi-
dence that a previous stillbirth or low-birth-weight infant significantly
increased the risk of a future stillbirth. Meyer and Comstock (5/)
provided examples of how the differential distribution of smoking and
other factors which are related to perinatal mortality, in a population
of women, can bias data (e.g., black women have higher perinatal
nortality rates than do white women, but black women smoke less
than white women do. Hence. nonsmokers will tend to include more
‘lack women, and smokers more white women. This will tend to
reduce any differences between the groups in mortality rates.) Meyer
and Comstock concluded, “Comparisons of mortality rates of smokers’
and nonsmokers’ babies should be made within subgroups according
'o parity, socioeconomic status, and other appropriate risk factors,
and not separated by birth weight.”

In three of the studies in which a significantly higher mortality risk
was demonstrated for the infants of smokers, adjustment for other
variables was performed. The results indicated that, after such ad-
justment, a significant independent association between cigarette
smoking and infant mortality persisted (13 and 15, 17, 8&1). Of the
studies which revealed no significant increase in mortality risks for
smokers’ infants, one (115) controlled for race alone. Hence, at. least
part of the discrepancy in results between the two groups of studies
may be explained by a lack of control of variables other than smoking.

Another possible, at least partial, explanation of the discrepancy
in results obtained by the two sets of studies is that cigarette smoke
may be more harmful to the fetuses of certain women than others.
Several] developing lines of evidence suggest that this may be the case:

I. Cigarette smoking and socioeconomic background.

Butler, et al. (25) noted that when data from the British Perinatal
Mortality Study are grouped by social class of the mother’s husband,
the late fetal plus neonatal mortality ratio for infants of smokers and
tonsmokers in the upper social classes I and IT is 1.10; the mortality
ratio for the entire sample was 1.28. Rush and Kass (82) reviewed the
British Perinatal Mortality Study, along with several other studies,
and noted that all have shown the strongest association between excess
Infant mortality and cigarette smoking among the infants of those

495-028 O—73—_10
131
mothers with lower Socioeconomic status, Comstock and Lundin (16
found excess mortality among smokers’ infants almost entirely cop.
fined to those whose fathers had a grammar school education or legs,
Several of the studies which revealed no significant, difference in mor.
tality among the infants of smokers and nonsmokers were conducteg
in predominately middle class populations (29, 100,115).

2. Cigarette smoking and previous obstetrical experience,

Peterson, et al. (72) had rigid criteria for entry into his study
population of 7,740 women. He included only those women who pre.
viously had healthy infants with a birth weight greater than 2509
grams. He found a significant decrease in birth weight among smokers’

with increased risk of a future stillbirth,
3. Cigarette smoking and genetic differences,

duce enhanced risk (82, 99, 115).

Available evidence Suggests that. if those women, who are already
likely to have small infants for reasons other than smoking, smoke
during pregnancy, their infants will be most unfavorably affected
This means that the women in the United States whose infants will
be most affected by cigarette smoking are those who have an unfavor-
able socioeconomic situation, have a history of previously unsuccessft]
pregnancies, and are black.

ExprertMenrar STuprIEs

Studies in Animals

Studies previously reviewed in the 1971 and 1979 reports on the
health consequences of smoking (107, 102) demonstrate that exposure
of rabbits and rats to tobacco smoke and to injections of large doses
of nicotine resulted in significantly increased late fetal and neonatal
mortality. Astrup (2) has recently studied the effect of continuous
exposure of pregnant rabbits to carbon monoxide on stillbirth rates,
He found a Significantly higher, dose-related incidence of stillbirths
and deaths within the first 94 hours of life among the offspring of the
experimental rabbits (table 4).

132
TaBLe 4.—E fect of carbon monoride exposure of pregnant rabbits on
birth weight and neonatal mortality

 

 

 

 

 

Group 1, Group 2, Group 3,
0 percent 8tol0 percent 16 to 18 percent
COHDb COHb COHb
Number of pregnant rabbits.___________ 17 14 17
Total number of babies... 116 81 123
Stillborn and babies died within first 24
hours___ 2-2 ry 28 344
(P<0.001)
1] percent.
“10 percent.
436 percent.

Source: Astrup, P. (2).

Studies in Humans

Some investigators have examined the causes of death among the
infants of smokers as compared with those of nonsmokers. Comstock,
etal. (77) found that infants of smokers died more frequently of as-
phyxia, atelectasis, and immaturity. Kullander and Kallen (43) found
ubruptio placentae significantly increased as a cause of death among
smokers’ infants. Butler and Alberman (74) found little difference in
the death rates for the infants of smokers and nonsmokers from iso-
immunization and malformations, but higher rates were found for
‘mokers’ infants in the groups in which death occurred before or dur-
ing labor, or in which death resulted from massive pulmonary hemor-
thage, or pulmonary infection. As the authors noted, “The latter three
‘re conditions known to be associated with small-for-dates babies.”
They pointed out that distribution of causes of death in the smoking
Troup could be accounted for almost entirely by the excess of low-birth-
weight babies. This su pports the conclusion that the mechanism which
iflects birth weight also influences mortality.

SIGNIFICANCE OF THE ASSOCIATION

The following calculation is offered to give some idea of the order of
Magnitude of increased late fetal and neonatal mortality associated
“ith cigarette smoking during pregnancy. If women who smoked dur-

133
ing pregnancy in the United States had an elevation in risk of 28 per.
cent for late fetal and neonatal mortality, as demonstrated by Butler,
etal. (75) for Britain, Scotland, and Wales, and if 20 percent of
pregnant women smoked throughout the pregnancy,’ the higher ris,
of stillbirth and neonatal death for the infants of mothers who smoke
cigarettes during pregnancy would account for approximately 4,600 of
the 87,263 stillbirth and neonatal deaths in the United States in 196g

Late Ferau anp NEONATAL DeatH Summary

A strong, probably causal association between cigarette smoking
and higher late fetal and infant mortality among smokers’ infants is
supported by the following evidence:

1. Twelve retrospective and prospective studies have revealed a sta.
tistically significant relationship between cigarette smoking and
an elevated mortality risk among the infants of smokers. In three
of these studies, of sufficient size to permit adjustment. for other
risk factors, a highly significant independent association between
smokng and mortality was established. Part of the discrepancy in
results between these studies and those in which a significant
association between smoking and infant mortality was not dem.
onstrated may be explained by a lack of adjustment for risk fac-
tors other than smoking.

2. Evidence is converging to suggest that cigarette smoking may be
more harmful to the infants of some women than others; this may
also, in part, explain the discrepancies between the results of the
studies in which a significantly higher mortality risk was shown
for the infants of smokers compared to those of nonsmokers and
the results of those studies in which significant differences in
mortality risk were not found.

3. Within groups of similar birth weight, the infants of nonsmokers
appear to have a higher mortality risk than do the infants of ciga-
rette smokers. This results from the fact that the infants of non-
smokers within such similar birth weight groups are on the
average gestationally less mature than the infants of cigarette
smokers. Available evidence indicates that within groups of sim-
iar gestational age, infants of lower birth weight experience a
higher mortality risk. Since the infants of cigarette smokers are

+ Based on extrapolation of data on smoking behavior change during pregnancy from
the British Perinatal Mortality Study. which probably yields a conservative estimate.

134
small-for-gestational age, one should expect that if the infants of
cigarette smokers and nonsmokers are compared within similar
gestational age classes, the infants of cigarette smokers would
have the higher mortality rate.

. The results of recent studies have documented a statistically sig-
nificant dose-response relationship between the number or amount
of cigarettes smoked and late fetal and neonatal mortality.

. New data suggest that if a woman gives up smoking by the fourth
month of pregnancy, she will have the same risk of incurring a
fetal or neonatal loss as a nonsmoker.

. Available evidence strongly supports cigarette smoking as one
cause of fetal growth retardation. The causes of excess deaths
among the infants of smokers are those associated with small-
for-dates babies.

- Data from experiments in animals have demonstrated that expo-
sure to tobacco smoke or some of its ingredients, such as nicotine
or carbon monoxide, results in a significant increase in late fetal
and or neonatal deaths.

- The results of studies in humans have shown that the fetus of
a smoking mother may be directly exposed to agents such as
carbon monoxide within tobacco smoke, at levels comparable to
those which have been shown to produce stillbirth in experimental
animals,

Sex Ratio

Although a number of small studies have found a slight, usually

statistically nonsignificant, increase in the proportion of female infants
born to smokers, the three largest studies of Underwood, ct al. (48,505
Pregnancies), Butler (15,791 pregnancies), and MacMahon (12,155
pregnancies) have found similar infant sex ratios among both smok-
ing and nonsmoking mothers, with the expected slight excess of males
among each (table).

Summary

Available evidence strongly indicates that maternal cigarette smok-

ing does not influence the sex ratio of newborn infants.

135
TABLE 5.—Proportion of male infants delivered to smoking and non.
smoking mothers

 

Proportion of male

 

infants Statistical
Author, reference Pregnancies ———-_~_____. significance
Smokers Non-
smokers
Underwood, et al. (100)_.. .____________ 48, 505 . 518 -519 None.
Butler and Alberman (14)___.__________ 15, 791 . 518 . 516 Do.
MacMahon, et al. (49)_____..__________ 12, 155 . 913 . 512 Do.
Kullander and Kallen (43)____________. 6, 363 . 515 . s0L Do.
Reinke and Henderson !(78)___.________ 3, 156 . 498 - 517 Do.
Frazier, et al.! (25)... 2 2,915 . 472 . 505 Do.
(P>0.05)
Kizer (42)_._-.. 2222 2, 095 . 502 . 493 None.
Herriott, et al. (88)_.-22 2-2 2, 745 . 492 517 Do.
Ravenholt, et al (77)_-....-___-_________ 2, 052 - 501 . 533° P<0.05
Lowe (46)_____-__-- ee 2, 042 . 532 . 529 None.
Russell, et al. (88).__-..___ 2-8. 2, 002 . 613 . 012 Do.

 

' Black women.

Congenital Malformations

Previous epidemiological studies which examined the relationship
between cigarette smoking and congenital malformations were te-
viewed in the 1971 and 1972 reports on the health consequences of
smoking (101, 102). Recently, the authors of the Ontario Perinatal
Mortality Study (66, 67), a retrospective study of 51,490 births, re-
ported no difference in malformation rate for the infants of smokers
and nonsmokers. The various studies of the association between ciga-
rette smoking and congenital malformation have differed significantly
with regard to study design. the type of population sampled. sample
size and number of infants with malformations, the definition of mal-
formation, and results (table 6).

Previous experimental work was reviewed in the 1971 and 1972
reports on the health consequences of smoking (/0/, 102). The chick
embryo has been employed in recent studies. The direct application of
nicotine to the embryo results in cephalic hematomas (26). malforma-
tions of the cervical vertebrae (93), and anomalies of the heart (27),
depending upon dose of nicotine and period of incubation in which
exposure occurs. Anomalies of the limbs of chicken embryos can also
be induced by exposure of the egg to high levels of carbon monox-

ide (4).
TABLE 6.—Helative risk of congenital malformation for infants of
cigarette smokers and nonsmokers, comparing available studies with
regard to study design, study population, sample size, number of
infants with malformations, and definition of malformation

 

Infants Relative

 

Author, Study design Study population Sample with risk Definition of
reference size malfor- SM/NS malformations
mations
Lowe (46). ....... Retrospective. Stillborn plus 24-hour 2, 042 23 1.36 Major.
deaths.
Comstock, etal. _.._- do._....... Neonatal deaths..__.._ 236 37 -31 Major, cause of
(17). death.
Yerushalmy (172). Prospective... Infants less than 695 59 57 Major.
2,500 g.
Ontario Depart- —- Retrospective. Stillborn plus Ist- 51, 490 1, 744 97
ment of Health week deaths plus
6), surviving infants.
Butlerand Al- LL _. do._....... Stillborn plus neo- 7, 123 1, 382 1.19 Major, cause of
berman (/4). natal deaths. death.
(a) Stillborn plus neo- 137 43 1.25
natal deaths
Kullander and Prospective. __ plus ainder Major and minor
Kallen (43). er deaths to age malformations.
(b) Surviving infants 4, 903 700 1.06
to age 1.
(a) 1 Stillborn plus 17, 418 86 £55 (4).
neonatal deaths t
and deaths to
Fedrick, et al. Retrospective. age 7,1 sur-
(4), vivors 2 to age
(b) Neonatal deaths t 7, 822 204 1.07 ().
(3-month
study).

 

 

' Autopsy-proven congenital cardiac malformation.
* Clinically determined congenital heart disease.

Congenital Malformation Sum mary

Given the considerable variation in study design, study population,
Sample size, number of affected infants, definition of malformation,
and results, no conclusions can be drawn about any relationship

between maternal cigarette smoking

the present time.

and congenital malformation at

137
Lactation

Introduction

The following section is a review of available evidence which bears
upon any interaction between cigarette smoking and lactation. Empha.
sis is placed upon the relationship of cigarette smoking to the quantity
of milk produced, to the presence of constituents of cigarette smoke
within the milk, and to effects upon the nursing infant mediated
through changes in either the quantity of milk available or the sub.
stances within the milk.

Epidemiological Studies

Underwood, et al. (99), in a study of 2,000 women from various
social and economic strata, observed a definite but statistically insig-
nificant trend toward more frequent inadequacy of breast milk pro-
duction among those smoking mothers who attempted to nurse
compared to nonsmokers.

Mills (52), in a study of 520 women, found that among women who
indicated either a desire to nurse or no desire to nurse yet continued
to nurse beyond 10 days, and who had delivered their first live-born
infant, the average pericd of nursing for mothers who smoked was
significautly shorter than for nonsmokers. Moreover, among the 24
mothers who had given up smoking during at least the final 3 months
of their pregnancies, the average length of nursing was identical to
that of the nonsmokers. There was no significant difference between
smokers and nonsmokers with regard to complete inability to nurse
their offspring. This study is difficult to interpret because the author
did not determine the reason(s) for the discontinuation of nursing
among the women.

Experimental Studies
Stvupres 1x ANIMALS
Nicotine

Influence on the Lactation Process

Blake and Sawver (77) studied the influence of subcutaneously
injected nicotine (4 mg. total over a 5-minute period) upon lactation
in the rat. They found that nicotine inhibited the suckling-induced

138
rise in prolactin. No effect of injected nicotine was demonstrated for
oxytocin secretion since milk release was not blocked.

Wilson (770) examined the effects of nicotine supplied through
drinking water (0.5, 1.0. and 2.0 mg. daily) on the weight gain of
nursing rats. Apparently. the nicotine had been available throughout
gestation as well. because the author commented on a reduction in litter
size among the experimental groups. more or less proportionate to the
dose of nicotine; hence, a prenatal effect could not have been dis-
tinguished from a postnatal one. Average birth weight was similar for
experimental and control groups. No difference in weight gain was seen
for any of the groups. The lack of impact on birth weight suggests
that dose was lower than that used in other studies.

Presence of Nicotine in the Milk

Hatcher and Crosby (32), using a frog bioassay, reported traces of
nicotine in cow’s milk 24 hours after the intramuscular injection of
0 mg./kg. and 5 hours after the injection of 0.5 mg./kg.

Evidence for an Effect Upon the Nursing Offspring

Hatcher and Crosby (32). found that 0.5 mng./kg. nicotine injected
into nursing cats had no apparent harmful effect upon the kittens.
Apparently 4.0 mg./kg. suppressed lactation. Kittens fed the milk
from the cow which had been injected with 5.0 mg./kg. nicotine were
also apparently unaffected.

Nitrosamines

Mohr (53) found that diethylnitrosamine and dibuty]nitrosamine,
when administered to lactating hamsters, were associated with the
development of typical tracheal papillary tumors in the young, sug-
gesting passage of these compounds in‘the milk. Although diethyl-
Nitrosamine and dibutylnitrosamine have not been identified in ciga-
rette smoke, many N-nitrosamines are potent carcinogens, and some
of them are present in cigarette smoke (37, 79).

Stupres 1x Humans

Nicotine and/or Tobacco Smoke

Influence on the Lactation Process

Emanuel (22) noted no reduction in milk production among 10 wet
hurses who were encouraged to smoke seven to 15 cigarettes daily;

139
Some were observed to inhale the smoke. Hatcher and Crosby (32)
noted that after a mother smoked seven cigarettes within 2 hours, it
was difficult to obtain a specimen of breast milk. Perlman, et al. (71)
found that of 55 women smokers with an adequate milk supply at the
beginning of his study, 11 (20 percent) of the women had an Inade-
quate supply at the time of discharge from the hospital. No relation.
ship was reported between the number of cigarettes smoked and the
likelihood of developing an inadequate milk supply. The authors’ im-
pression was that there was no greater proportion with an inadequate
milk supply among smokers than among nonsmokers, but no cor.
roborating data were supplied.

Presence of Nicotine in the Milk

Hatcher and Crosby (32) found, using a frog bioassay, that the
milk of a woman collected after she had smoked seven cigarettes in 9
hours contained approximately 0.6 mg./liter nicotine. Emanuel (22),
using a leech bioassay, studied excretion of nicotine in the milk of wet
nurses who were encouraged to smoke for the experiment. After the
subjects had smoked six to 15 cigarettes over a 1- to 2-hour period, the
author found nicotine in their milk 4 to 5 hours after smoking, with a
maximum concentration of 0,03 mg./liter. Bisdom (70) demonstrated
nicotine in the milk of a mother who smoked 20 cigarettes a day,
Thompson (97) found approximately 0.1 mg./liter of nicotine in the
milk of a mother who smoked nine cigarettes a day (plus three pipe-
fuls). Perlman, et al. (71), using a Daphnia bioassay, demonstrated
nicotine in the milk of all women who smoked in their study. Moreover,
they found a direct dose-relationship between concentration of nicotine
and the number of cigarettes smoked. No comment is made by the
authors on the possible inaccuracy introduced by examining only the
residual milk following nursing, but it is well known that the composi-
tion of the fore milk and hind milk is different and perhaps the
concentration of nicotine also differs.

Evidence for a Clinical Effect Upon the Offspring

Emanuel (22) noted that among the infants in his study, loose stools
were observed only in the one whose wet nurse had smoked 20 ciga-
rettes in the previous 4 hours. Bisdom (20) observed a case of “nico-
tine poisoning” in a 6-week-old infant whose mother smoked 20 ciga-
rettes a day. The symptoms included: restlessness, vomiting, diarrhea.
and tachycardia. Nicotine was demonstrated in the milk, and the
symptoms abated when smoking was stopped. Greiner (30) also de-
scribed a case of possible nicotine poisoning in a 3-week-old nursling

140
whose mother smoked 35 to 40 cigarettes a day. The symptoms included
vomiting and loose stools. Following the curtailment of smoking, the
symptoms gradually abated over a 3-day period. Perlman, et al. (77)
noted no effect of smoking on the weight gain of the infants of the
smokers in their study. Furthermore, no untoward symptoms were
observed. They therefore doubted an effect of smoking on lactation.
They noted that the dose received by the infants was beneath the toxic
level as computed from adult experience, and this accorded with their
clinical observations. The fact that they admitted to the study only
women with an apparently adequate milk supply may have affected
their results. The authors suggested that perhaps the lack of effect of
smoking upon lactation might represent the development of tolerance
to nicotine, as both the mother and the offspring had been exposed
throughout the pregnancy.

VITAMIN C

Venulet (105, 106, 107), in a series of studies, demonstrated that
the level of vitamin C was reduced in the milk of smoking mothers as
compared with nonsmokers. The clinical significance of this observa-
tion has not been evaluated.

Lactation Summary

1. The two pertinent epidemiological studies suggest. a possible in-
fluence of smoking upon the adequacy of milk supply However,
with only limited numbers of women and without control of other
potentially significant variables, no conclusions can be drawn.

2. Studies in rats have demonstrated that nicotine can interfere with
suckling-induced rise in prolactin. The relevance for humans
is uncertain.

3. Evidence exists that nicotine passes into breast milk. No clear
evidence for an acute effect upon the nursing infant is available.
Potential chronic effects haye not been studied.

4. New evidence from experiments with mice suggests that. nitros-
amines, known carcinogens, pass through the milk to suckling
young.

141
Preeclampsia

Previous epidemiological studies of the relationship between cig
arette smoking and preeclampsia were reviewed in the 1971 and 1979
reports on the health consequences of smoking ( 101, 102) and form the
basis of the following statements:

The results of several large prospective and retrospective Studies
indicate a statistically significant lower incidence of Preeclampsia
among smoking women (14, 43, 100). The results of one large retro.
Spective study demonstrated a significant inverse relationship between
the incidence of preeclampsia and the number of cigarettes smoked
(100). When other risk factors, such as parity, social class, maternal
weight before the pregnancy, and maternal] weight gain during the

Scotland (14, 41, 46, 83), The United States (100, 118), Venezuelg
(42), and Sweden (43). If a maternal smoker does develop preeclamp.
sia, however, available data suggest that her infant has a higher mor.

tality risk than does the infant of a nonsmoker with preeclampsia
(21, 83),

Summary

1. Available evidence indicates that maternal] cigarette smoker
have a significantly lower risk of developing preeclampsia as
compared to nonsmokers,

2. Ifa woman who smokes cigarettes during pregnancy does develop
preeclampsia, her infant has-a higher mortality risk than the
infant of a nonsmoker with preeclampsia.

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