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Effect of smoking on cadmium and lead concentrations in human amniotic fluid
Toxicology Letters,
19 (1983) 327-331
327
Elsevier
EFFECT
OF SMOKING
IN HUMAN (Cadmium; C.-P.
ON CADMIUM
AMNIOTIC
FLUID
lead; amniotic
fluid;
SIEGERS,
J.R.
JUNGBLUT,
AND LEAD
CONCENTRATIONS
smoking)
F. KLINK*
and F. OBERHEUSER*
Department of Toxicology and *Department of Gynecology and Obstetrics, Medical School of Liibeck, D-2400 Liibeck (F.R. G.) (Received
July 9th,
(Revision
received
(Accepted
August
1983) August
lOth, 1983)
15th, 1983)
SUMMARY The amniotic vestigated
fluids of 155 pregnant
on their cadmium
fluid of non-smokers was a correlation centrations smokers. pregnancy
amounted
between
were found
non-smokers
ranging
and the amniotic
(n= 128) and smokers
between
23.98k9.41
were seen between
women
Thus, remain
were in-
to 7.29k2.39
gg/l.
Moreover,
there
and Cd levels. With Pb, higher con-
for non-smokers
age, week of pregnancy,
Cd or Pb concentrations. fluid of smoking
consumption rig/l
(n=27),
The mean k s range of Cd in the amniotic
to 2.58 i 1.36 rig/l,, that of smokers
the extent of daily cigarette
No correlations
Cd levels in the amniotic
women,
(Cd) and lead (Pb) concentrations.
the maternal
and 21.53 k7.16
blood
pressure,
pg/l
for
disorders
of
and fetal risks of the higher
unanswered.
INTRODUCTION
Several recent reports have linked Cd concentration to cigarette smoking and to hypertension [ 1,2]. As smoking may affect human reproduction, e.g., by increasing the risk of spontaneous abortion [3], retarding fetal development [4] and inducing pregnancy complications, [5]. Cd may be one of the factors involved, as Cd in animals has also been found to evoke fetal growth retardation, developmental disorders and fetal death [6]. Since the smoking of cigarettes significantly contributes to the total body burden of Cd, questions have arisen concerning the disposition of Cd in pregnant women who smoke. Some investigations were performed with regard to the concentrations of Cd and some other heavy metals in the placenta as well as maternal and cord blood at delivery [7]. Our interest focussed on the question whether the amniotic fluid as part of the maternal-fetoplacental unit contains higher concentrations of Cd and Pb as a consequence of smoking. Moreover, diagnostic amniocentesis between the 16th and 38th week of gestation allows a better control of the distribution of Cd in the fetoplacental unit.
0378-4274/83/$
03.00
0 Elsevier
Science Publishers
B.V.
328
MATERIALS
AND METHODS
155 pregnant women, 27 smokers and 128 non-smokers, were included in this study. They resided in or very near Ltibeck. Samples of amniotic fluid were taken for diagnostic reasons during early (16th-20th week) or late (32nd-38th week) pregnancy. The samples were prepared for analysis of Cd and Pb by means of acid digestion. To l-2 ml samples of amniotic fluid a 1:l mixture of 5-10 ml perchloric acid (70%) and nitric acid (65%) was added and heated until dry. After drying, the samples were reconstituted with nitric acid and bidistilled water and analyzed by means of atomic absorption spectroscopy. An atomic absorption spectrophotometer (Model 4000, Perkin Elmer Corp.) equipped with a graphite furnace was used to quantitate Cd and Pb. The within-run precision of Cd analysis was V = 8.2% and of Pb analysis V = 10.8%. The detection limit was 0.2 pg/l. Statistical analyses were performed using Student’s t-test with P
The concentrations of Cd in the amniotic fluid of 155 women are depicted in Fig. 1. In non-smokers (n = 128) the Cd values ranged between 0.5 and 8pg/l, in smokers (n = 27) between 1.8 and 11.4 pg/l. The mean -+ s values of Cd for both groups are given in Table I indicating a threefold higher concentration of Cd in smokers (7.29 -t 2.39 rig/l)) compared with non-smokers (2.58 + 1.36 ng/l). The data (Fig. 2) suggest that there is obviously a correlation between daily cigarette consumption and the amniotic Cd concentrations. With Pb higher concentrations were found in the amniotic fluid samples, the means t s ranges for both smoking and non-smoking pregnant women are given in Table I; as can be seen, no differences were found between the groups. Correlation analyses revealed no influence of age or the week of gestation on amniotic Cd and Pb concentrations. Furthermore no correlations were found between
TABLE MEAN
1 CADMIUM
155 PREGNANT
(Cd) AND LEAD
(Pb) CONCENTRATIONS
IN THE AlMNIOTIC
WOMEN
Group
n
Cd
Pb (ng/ml;
Non-smokers Smokers “P
(Student’s
128 21 t-test).
2.58i 7.29i
1.36 2.39”
x & s) 23.98 + 9.41 21.5327.16
FLUID
OF
329
Cd ng/ml
15--
. . .. .
lb
.
..s; .
. ..
E i
96 i
5--
. .
. . . . .
Fig. 1. Cadmium
I
1
NS
S
concentrations
in the amniotic
fluids of smoking
(S) and non-smoking
(NS) women.
Cd ng/ml
n=ll
n-5
n=7
(ii?SX)
li9
lo’-19
-20’
Cigarettes/day Fig. 2. Cadmium consumption.
levels in the amniotic
fluid of smoking
women
in relation
to daily cigarette
330
Cd and Pb levels and blood pressure of the pregnant of pregnancy, fetal abnormalities and abortion.
women
as well as disorders
DISCUSSION
Our results indicate significantly higher Cd concentrations in the amniotic fluid of women who continue smoking during pregnancy. Moreover, we found a dependence between daily cigarette consumption and Cd levels. These data are in accordance with recent findings of Fochtman and coworkers [8] who also reported higher Cd-levels in the amniotic fluid of smoking women which, in addition, were correlated to hypertension. Although our data showed more pronounced differences between Cd-concentration of smokers and non-smokers, we did not find any correlation to the incidence of hypertension. In a recent paper Kuhnert and coworkers [7] reported on a 59% increase of Cd in the maternal blood and a 32% increase in the placenta due to smoking. As the levels of Cd in the cord blood were lower than in the maternal blood, these authors concluded that the placenta acts as a barrier to the transfer of Cd to the fetus. The assumption that the fetus does not receive much Cd from the maternal exposure must be corrected on the basis of our data. Undoubtedly, most of the Cd accumulates in the placenta, this barrier, however, does not completely protect the fetus against the exposure to Cd, especially during the early period of gestation when the placenta is less well developed. In contrast to Kuhnert and coworkers [7] who collected their data at delivery, our results with amniotic fluid measurements reflect the exposure to Cd during the whole gestation period. Nevertheless, we did not find any correlation between Cd concentrations and the week of gestation. Furthermore, this level of exposure to Cd does not seem to be associated with adverse effects during pregnancy. However, an increased exposure to Cd, a metal without known biological functions, must be regarded as an incalculable risk for the mother and the fetus. Moreover, the fact that Cd accumulates in the placenta [7] may be hazardous to the fetus. Accumulation of Cd in the placenta might impair its function and thus be embryotoxic. Fetal growth retardation and weight loss as a consequence of cigarette smoking during pregnancy [4] may be related to both carbon monoxide and Cd-induced alterations in placental function. With Pb, on the other hand, smoking seems not to be an important contribution to the total body burden, since the ubiquitous environmental exposure to Pb is obviously more pronounced than to Cd in our region. In conclusion, in pregnant women who smoke, threefold higher Cd-levels in the amniotic fluid were found indicating that the placenta does not guarantee complete protection against increased exposure to Cd. We therefore plan to continue our investigations to clarify the maternal and fetal risks of this increased exposure to Cd due to smoking.
331
ACKNOWLEDGEMENTS
The technical assistance of Mrs. F. Siegers and M.U. Landfried appreciated.
is gratefully
REFERENCES
1 S.G.
Schafer
and .W. Forth,
Cadmium-Bewertung
eines Schadstoffs,
Dtsch.
Arzteblatt,
79 (1982)
39-57. 2 B.G. Armstrong
and G. Kazantzis,
3 D.V. Himmelberger, currence
The mortality
of cadmium
B.W. Brown and E.N. Cohen,
of spontaneous
abortion
and
congenital
Cigarette
workers, smoking
abnormality,
Lancet
during
Am.
(1983) 1425-1427.
pregnancy
and the oc-
J. Epidemiol.,
108 (1978)
470-479. 4 M.G. Meyer, B.S. Jonas and J.A. Tonascia, ing pregnancy, 5 J. Andrews
Am. J. Epidemiol.,
and J.M. McGarry,
Br. Commonw., 6 N. Chernoff, blood,
events associated
with maternal
smoking
dur-
A community
study of smoking
in pregnancy,
J. Obstet.
Gynaecol.
79 (1972) 1057-1073. Teratogenic
7 P.M. Kuhnert, cord
Perinatal
103 (1976) 464-476.
effects
B.R. Kuhnert, and placental
of cadmium
S.F. Bottoms
tissues
in the rats,
Teratology,
8 (1973) 29-32.
and P. Erhard,
Cadmium
levels in maternal
of pregnant
women
who smoke,
Am.
J. Obstet.
blood, Gynecol.,
fetal 142
(1982) 1021-1025. 8 F.W.
Fochtman,
icologist,
C.F.
2 (1982) 5.
Kritko
and C.L.
Winek,
Cadmium
concentrations
in amniotic
fluids,
Tox-
19 (1983) 327-331
327
Elsevier
EFFECT
OF SMOKING
IN HUMAN (Cadmium; C.-P.
ON CADMIUM
AMNIOTIC
FLUID
lead; amniotic
fluid;
SIEGERS,
J.R.
JUNGBLUT,
AND LEAD
CONCENTRATIONS
smoking)
F. KLINK*
and F. OBERHEUSER*
Department of Toxicology and *Department of Gynecology and Obstetrics, Medical School of Liibeck, D-2400 Liibeck (F.R. G.) (Received
July 9th,
(Revision
received
(Accepted
August
1983) August
lOth, 1983)
15th, 1983)
SUMMARY The amniotic vestigated
fluids of 155 pregnant
on their cadmium
fluid of non-smokers was a correlation centrations smokers. pregnancy
amounted
between
were found
non-smokers
ranging
and the amniotic
(n= 128) and smokers
between
23.98k9.41
were seen between
women
Thus, remain
were in-
to 7.29k2.39
gg/l.
Moreover,
there
and Cd levels. With Pb, higher con-
for non-smokers
age, week of pregnancy,
Cd or Pb concentrations. fluid of smoking
consumption rig/l
(n=27),
The mean k s range of Cd in the amniotic
to 2.58 i 1.36 rig/l,, that of smokers
the extent of daily cigarette
No correlations
Cd levels in the amniotic
women,
(Cd) and lead (Pb) concentrations.
the maternal
and 21.53 k7.16
blood
pressure,
pg/l
for
disorders
of
and fetal risks of the higher
unanswered.
INTRODUCTION
Several recent reports have linked Cd concentration to cigarette smoking and to hypertension [ 1,2]. As smoking may affect human reproduction, e.g., by increasing the risk of spontaneous abortion [3], retarding fetal development [4] and inducing pregnancy complications, [5]. Cd may be one of the factors involved, as Cd in animals has also been found to evoke fetal growth retardation, developmental disorders and fetal death [6]. Since the smoking of cigarettes significantly contributes to the total body burden of Cd, questions have arisen concerning the disposition of Cd in pregnant women who smoke. Some investigations were performed with regard to the concentrations of Cd and some other heavy metals in the placenta as well as maternal and cord blood at delivery [7]. Our interest focussed on the question whether the amniotic fluid as part of the maternal-fetoplacental unit contains higher concentrations of Cd and Pb as a consequence of smoking. Moreover, diagnostic amniocentesis between the 16th and 38th week of gestation allows a better control of the distribution of Cd in the fetoplacental unit.
0378-4274/83/$
03.00
0 Elsevier
Science Publishers
B.V.
328
MATERIALS
AND METHODS
155 pregnant women, 27 smokers and 128 non-smokers, were included in this study. They resided in or very near Ltibeck. Samples of amniotic fluid were taken for diagnostic reasons during early (16th-20th week) or late (32nd-38th week) pregnancy. The samples were prepared for analysis of Cd and Pb by means of acid digestion. To l-2 ml samples of amniotic fluid a 1:l mixture of 5-10 ml perchloric acid (70%) and nitric acid (65%) was added and heated until dry. After drying, the samples were reconstituted with nitric acid and bidistilled water and analyzed by means of atomic absorption spectroscopy. An atomic absorption spectrophotometer (Model 4000, Perkin Elmer Corp.) equipped with a graphite furnace was used to quantitate Cd and Pb. The within-run precision of Cd analysis was V = 8.2% and of Pb analysis V = 10.8%. The detection limit was 0.2 pg/l. Statistical analyses were performed using Student’s t-test with P
The concentrations of Cd in the amniotic fluid of 155 women are depicted in Fig. 1. In non-smokers (n = 128) the Cd values ranged between 0.5 and 8pg/l, in smokers (n = 27) between 1.8 and 11.4 pg/l. The mean -+ s values of Cd for both groups are given in Table I indicating a threefold higher concentration of Cd in smokers (7.29 -t 2.39 rig/l)) compared with non-smokers (2.58 + 1.36 ng/l). The data (Fig. 2) suggest that there is obviously a correlation between daily cigarette consumption and the amniotic Cd concentrations. With Pb higher concentrations were found in the amniotic fluid samples, the means t s ranges for both smoking and non-smoking pregnant women are given in Table I; as can be seen, no differences were found between the groups. Correlation analyses revealed no influence of age or the week of gestation on amniotic Cd and Pb concentrations. Furthermore no correlations were found between
TABLE MEAN
1 CADMIUM
155 PREGNANT
(Cd) AND LEAD
(Pb) CONCENTRATIONS
IN THE AlMNIOTIC
WOMEN
Group
n
Cd
Pb (ng/ml;
Non-smokers Smokers “P
(Student’s
128 21 t-test).
2.58i 7.29i
1.36 2.39”
x & s) 23.98 + 9.41 21.5327.16
FLUID
OF
329
Cd ng/ml
15--
. . .. .
lb
.
..s; .
. ..
E i
96 i
5--
. .
. . . . .
Fig. 1. Cadmium
I
1
NS
S
concentrations
in the amniotic
fluids of smoking
(S) and non-smoking
(NS) women.
Cd ng/ml
n=ll
n-5
n=7
(ii?SX)
li9
lo’-19
-20’
Cigarettes/day Fig. 2. Cadmium consumption.
levels in the amniotic
fluid of smoking
women
in relation
to daily cigarette
330
Cd and Pb levels and blood pressure of the pregnant of pregnancy, fetal abnormalities and abortion.
women
as well as disorders
DISCUSSION
Our results indicate significantly higher Cd concentrations in the amniotic fluid of women who continue smoking during pregnancy. Moreover, we found a dependence between daily cigarette consumption and Cd levels. These data are in accordance with recent findings of Fochtman and coworkers [8] who also reported higher Cd-levels in the amniotic fluid of smoking women which, in addition, were correlated to hypertension. Although our data showed more pronounced differences between Cd-concentration of smokers and non-smokers, we did not find any correlation to the incidence of hypertension. In a recent paper Kuhnert and coworkers [7] reported on a 59% increase of Cd in the maternal blood and a 32% increase in the placenta due to smoking. As the levels of Cd in the cord blood were lower than in the maternal blood, these authors concluded that the placenta acts as a barrier to the transfer of Cd to the fetus. The assumption that the fetus does not receive much Cd from the maternal exposure must be corrected on the basis of our data. Undoubtedly, most of the Cd accumulates in the placenta, this barrier, however, does not completely protect the fetus against the exposure to Cd, especially during the early period of gestation when the placenta is less well developed. In contrast to Kuhnert and coworkers [7] who collected their data at delivery, our results with amniotic fluid measurements reflect the exposure to Cd during the whole gestation period. Nevertheless, we did not find any correlation between Cd concentrations and the week of gestation. Furthermore, this level of exposure to Cd does not seem to be associated with adverse effects during pregnancy. However, an increased exposure to Cd, a metal without known biological functions, must be regarded as an incalculable risk for the mother and the fetus. Moreover, the fact that Cd accumulates in the placenta [7] may be hazardous to the fetus. Accumulation of Cd in the placenta might impair its function and thus be embryotoxic. Fetal growth retardation and weight loss as a consequence of cigarette smoking during pregnancy [4] may be related to both carbon monoxide and Cd-induced alterations in placental function. With Pb, on the other hand, smoking seems not to be an important contribution to the total body burden, since the ubiquitous environmental exposure to Pb is obviously more pronounced than to Cd in our region. In conclusion, in pregnant women who smoke, threefold higher Cd-levels in the amniotic fluid were found indicating that the placenta does not guarantee complete protection against increased exposure to Cd. We therefore plan to continue our investigations to clarify the maternal and fetal risks of this increased exposure to Cd due to smoking.
331
ACKNOWLEDGEMENTS
The technical assistance of Mrs. F. Siegers and M.U. Landfried appreciated.
is gratefully
REFERENCES
1 S.G.
Schafer
and .W. Forth,
Cadmium-Bewertung
eines Schadstoffs,
Dtsch.
Arzteblatt,
79 (1982)
39-57. 2 B.G. Armstrong
and G. Kazantzis,
3 D.V. Himmelberger, currence
The mortality
of cadmium
B.W. Brown and E.N. Cohen,
of spontaneous
abortion
and
congenital
Cigarette
workers, smoking
abnormality,
Lancet
during
Am.
(1983) 1425-1427.
pregnancy
and the oc-
J. Epidemiol.,
108 (1978)
470-479. 4 M.G. Meyer, B.S. Jonas and J.A. Tonascia, ing pregnancy, 5 J. Andrews
Am. J. Epidemiol.,
and J.M. McGarry,
Br. Commonw., 6 N. Chernoff, blood,
events associated
with maternal
smoking
dur-
A community
study of smoking
in pregnancy,
J. Obstet.
Gynaecol.
79 (1972) 1057-1073. Teratogenic
7 P.M. Kuhnert, cord
Perinatal
103 (1976) 464-476.
effects
B.R. Kuhnert, and placental
of cadmium
S.F. Bottoms
tissues
in the rats,
Teratology,
8 (1973) 29-32.
and P. Erhard,
Cadmium
levels in maternal
of pregnant
women
who smoke,
Am.
J. Obstet.
blood, Gynecol.,
fetal 142
(1982) 1021-1025. 8 F.W.
Fochtman,
icologist,
C.F.
2 (1982) 5.
Kritko
and C.L.
Winek,
Cadmium
concentrations
in amniotic
fluids,
Tox-