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doi: 10.1111/ppe.12163

Maternal Cigarette, Alcohol, and Coffee Consumption

in Relation to Risk of Clubfoot
Martha M. Werler,a Mahsa M. Yazdy,a James R. Kasser,b Susan T. Mahan,b Robert E. Meyer,c
Marlene Anderka,d Charlotte M. Druschel,e Allen A. Mitchella
a

Slone Epidemiology Center, Boston University

Department of Orthopaedic Surgery, Boston Childrens Hospital

Massachusetts Birth Defects Monitoring Program, Massachusetts Department of Public Health, Center for Birth Defects Research and
Prevention, Boston, MA
c

North Carolina Birth Defects Monitoring Program, State Center for Health Statistics, Raleigh, NC
e

Congenital Malformations Registry, New York State Department of Health, Albany, NY

Abstract
Background: Clubfoot is associated with maternal cigarette smoking in several studies, but it is not clear if this
association is confined to women who smoke throughout the at-risk period. Maternal alcohol and coffee drinking
have not been well studied in relation to clubfoot.
Methods: The present study used data from a population-based casecontrol study of clubfoot conducted in Massachusetts, New York, and North Carolina from 2007 to 2011. Mothers of 646 isolated clubfoot cases and 2037
controls were interviewed about pregnancy events and exposures, including the timing and frequency of cigarette
smoking, alcohol intake, and coffee drinking.
Results: More mothers of cases than controls reported smoking during early pregnancy (28.9% vs. 19.1%). Of
women who smoked when they became pregnant, those who quit in the month after a first missed period had a
40% increase in clubfoot risk and those who continued to smoke during the next 3 months had more than a
doubling in risk, after controlling for demographic factors, parity, obesity, and specific medication exposures.
Adjusted odds ratios for women who drank >3 servings of alcohol or coffee per day throughout early pregnancy
were 2.38 and 1.77, respectively, but the numbers of exposed women were small and odds ratios were unstable.
Conclusions: Clubfoot risk appears to be increased for offspring of women who smoke cigarettes, particularly those
who continue smoking after pregnancy is recognisable, regardless of amount. For alcohol and coffee drinkers,
suggested increased risks were only observed in higher levels of intake.
Keywords: Pregnancy, malformation, clubfoot, alcohol, smoking, coffee.
Clubfoot involves congenital malpositions of the
bones and soft tissue of the ankle and foot. When the
foot cannot be manipulated by hand into normal position, the anomaly is considered a structural clubfoot,
which requires serial casting and possibly surgery to
correct.1,2 Even after correction in infancy, approximately 45% of cases relapse into malposition and
necessitate continued orthopaedic treatment.3 On
average, adults with treated clubfoot have poorer
mobility, flexion, comfort, and quality of life.4 Structural clubfoot develops in early gestation, and a vascular disruption pathogenesis is one mechanism that has
Correspondence:
Martha M. Werler, Slone Epidemiology Center, Boston
University, 1010 Commonwealth Avenue, Boston, MA 02215,
USA.
E-mail: werler@bu.edu

2014 John Wiley & Sons Ltd

Paediatric and Perinatal Epidemiology, 2015, 29, 310

been hypothesised.510 Exposures that may result in

vascular disruption, therefore, should be explored as
potential risk factors.
Maternal cigarette smoking has been shown
in several studies to increase clubfoot risk in
offspring,1115 but alcohol use and coffee drinking have
not been adequately explored. Cigarette smokers,
alcohol users, and coffee drinkers often change the
patterns of these exposures in early pregnancy,1618
when structural clubfoot develops. Thus, examination
of these exposures as risk factors for clubfoot requires
consideration of the timing of such changes. For
example, despite the many studies that have identified
increased risks for clubfoot in relation to maternal
cigarette smoking, it is not clear if the association is
present among women who quit smoking after pregnancy is recognisable.

M. M. Werler et al.

The present analysis used data from a populationbased casecontrol study of structural clubfoot. The
study was specifically designed to assess changes in
cigarette, alcohol, and coffee exposures, allowing
examination of timing and frequency.

Methods
Cases of clubfoot in this casecontrol study were
ascertained from Massachusetts, North Carolina, and
New York birth defects registries during the years
200711. Infants <11 months of age with a diagnosis of
talipes equinovarus or clubfoot without a known chromosomal anomaly, inherited syndrome, bilateral renal
agenesis, Potter syndrome, or neural tube defect were
eligible. For controls, children born in the same years
as cases but without known malformations were
sampled from birth certificates (MA and NC) or the
same birth hospital as cases (NY). Study nurses interviewed mothers of cases and controls by telephone
within 12 months after delivery, using a computerised,
standardised questionnaire on demographic factors,
reproductive history, and pregnancy events and exposures. The institutional review boards at Boston
University and the state health departments in Massachusetts, North Carolina, and New York approved the
study protocol. Details of the study methods, including ascertainment and inclusion criteria, have previously been reported.19
Structural clubfoot diagnosis was confirmed by
orthopaedist review of medical records (77%) or
based on maternal report of 3 foot castings (23%).
Cases were further classified as isolated or multiple
(additional major malformations noted by birth defect
registry or in medical records). A heart murmur
without supporting evidence of a structural heart
abnormality was not considered a major anomaly. For
the purposes of this analysis, the case group was confined to those with confirmed, structural, and isolated
clubfoot.
Mothers were asked about exposures for the time
period beginning 1 month before the last menstrual
period (LMP) to delivery. For alcohol and coffee
intake, women were asked if they ever drank more
than two drinks in 1 day. Women who reported
no were classified as non-drinkers. Women who
answered yes were asked how often they drank and
the number of drinks per day when they did drink
before becoming pregnant. Women were then asked if
there was any change after becoming pregnant, and, if

so, when the change occurred and what the new frequency and number of drinks per drinking day were.
For cigarette smoking, women were asked if they had
ever smoked cigarettes, followed by the same series of
questions as described for alcohol and coffee.
In addition to questions on behaviours, women
were asked about their age, years of education,
marital status, race/ethnicity, number of previous
pregnancies and births, height, pre-pregnancy weight,
and the timing and frequency of use of specific medications. They were also asked if any of the babys relatives were born with clubfoot, and, if so, which
relative(s).
Limb development occurs between the 4th and the
16th week after the LMP. Using the obstetric rubric for
gestational timing of 28-day lunar months (LMs)
beginning with the LMP, this interval corresponds to
the second through the fourth LMs of pregnancy,
which we refer to as the early pregnancy. Women
with any exposure in that interval were compared
with those with no exposure. In addition, mutually
exclusive categories were created: exposure in LM 2
only (LM 2 quitters), exposure in LM 2 and 3 only
(LM 3 quitters), and exposure in LM 2 through LM 4.
The average number of cigarettes smoked per day was
calculated within each of the timing categories as
follows: number of days exposed times the number of
cigarettes smoked per day divided by the total
number of days in the exposure window. For
example, a woman who smoked 20 cigarettes per day
until she quit on the 35th day after her LMP would be
considered exposed in the LM 2 only category, and
her average number of cigarettes for that interval
would be (20 cigarettes 7 days)/28 days = 5/day.
Low and high levels were considered to be 10 per
day and >10 per day, respectively. For alcohol and
coffee exposures, the reported average number of
drinks per drinking day was calculated following the
same rubric described above for smoking, except low
and high levels were 3 drinks and >3.0 drinks per
drinking day, respectively.
Associations between clubfoot and early pregnancy
cigarette smoking, alcohol intake, and coffee drinking
were estimated with logistic regression models.
Unadjusted odds ratios and 95% confidence intervals
(CI) were estimated. Adjusted ORs (aORs) included
terms for previously reported clubfoot risk factors,19,20
including study centre, child sex, maternal race/
ethnicity, primiparity, obesity, any use of clomiphene
or fertility hormones during the month before or
2014 John Wiley & Sons Ltd
Paediatric and Perinatal Epidemiology, 2015, 29, 310

Cigarettes, alcohol, coffee, and clubfoot

2 months after the LMP, and any uses of opioids,
selective serotonin reuptake inhibitor, ondansetron,
phenergan, pseudoephedrine, diphenhydramine, amoxicillin, and salicylates during the second, third, or
fourth LM. Combinations of cigarette, alcohol, and
coffee exposures were also evaluated. Comparisons
were further stratified according to family history of
clubfoot in a first-degree relative.

Table 1. Distribution of demographic and reproductive factors

among 646 isolated clubfoot cases and 2037 controls

Descriptive factors
Childs sex
Maternal age
(years)

Results
The mothers of 72% of eligible cases and 63% of eligible controls participated in the study. Among the
677 clubfoot cases, 95% had no other major malformations and were included in the present analysis. These
646 cases were compared with the 2037 control subjects. Compared with controls, a higher percentage of
cases were male, from the Massachusetts study site,
first-born, and had mothers who were white nonHispanic and overweight or obese (body mass index
of 25.0 or higher) (Table 1). Cases were >10 times as
likely as controls to have a parent or sibling affected
with clubfoot.
Among early pregnancy smokers, approximately
40% quit in LM 2, 9% quit in LM 3, and 50% continued to smoke during LM 2 through 4 (Table 2).
With the exception of women who smoked 10 cigarettes per day before quitting in LM 3, aORs were
increased. The largest increases in risk were observed
for women who smoked during LM 2 through 4; for
10 cigarettes per day, the aOR was 2.21 [95% CI 1.61,
3.02], and for >10 cigarettes/day it was 2.58 [95% CI
1.38, 4.81]. Women who quit smoking in LM 2 had
more modestly increased risks of clubfoot, regardless
of the level of smoking. Among LM 2 quitters, the
aOR for both levels combined was 1.41 [95% CI 1.02,
1.95].
Most women who drank alcohol in early pregnancy
quit in LM 2 and relatively few quit in LM 3. Higher
proportions of case mothers were LM 2 quitters than
control mothers, and aORs for both 3 and >3 drinks/
drinking day were slightly elevated. When combined,
any drinking among LM 2 quitters was associated
with a 1.33-fold increased risk [95% CI 0.98, 1.82]. No
increase in clubfoot risk was evident for LM 3 quitters, although numbers were small. Less than 1% of
women reported use LM 2 through 4, but case
mothers were more than twice as likely to report an
average >3 drinks/drinking day during this period
(aOR, 2.38; 95% CI 0.66, 8.52).
2014 John Wiley & Sons Ltd
Paediatric and Perinatal Epidemiology, 2015, 29, 310

Maternal
education
Mother living
with childs
father
Race ethnicity

Maternal
residence
First-born
Pre-pregnancy
body mass
index (kg/m2)

Clubfoot in
parent or
sibling

Male
Female
<20
2024
2529
3034
35
Unknown
<12 years
12 years
13 years
Yes
No
Unknown
White, non-Hispanic
Hispanic
Black
Other
New York
North Carolina
Massachusetts
Yes
No
<18.5
18.524.9
25.029.9
30.0
Unknown
Yes
No

Cases
n (%)

Controls
n (%)

466 (72.1)
180 (27.9)
19 (2.9)
132 (20.4)
178 (27.6)
183 (28.3)
134 (20.7)
0 (0.0)
80 (12.4)
163 (25.2)
403 (62.4)
553 (85.6)
92 (14.2)
1 (0.2)
472 (73.1)
72 (11.1)
82 (12.7)
20 (3.1)
202 (31.3)
265 (41.0)
179 (27.7)
313 (48.5)
333 (51.6)
23 (3.6)
297 (46.0)
175 (27.1)
134 (20.7)
17 (2.6)
76 (11.8)
570 (88.2)

1006 (49.4)
1031 (50.6)
107 (5.3)
369 (18.1)
536 (26.3)
568 (27.9)
452 (22.2)
5 (0.2)
283 (13.9)
456 (22.4)
1297 (63.7)
1730 (84.9)
305 (15.0)
2 (0.1)
1339 (65.7)
246 (12.1)
342 (16.8)
109 (5.4)
568 (27.9)
1014 (49.8)
455 (22.3)
814 (40.0)
1223 (60.0)
87 (4.3)
1080 (53.0)
451 (22.1)
360 (17.7)
59 (2.9)
15 (0.7)
2022 (99.3)

Like cigarette smoking, coffee drinkers in early

pregnancy were most likely to continue through LM
4. The timing and amount of coffee intake were similarly distributed among case and control mothers,
with one exception. The aOR for women who
reported >3 drinks/drinking day for LM 2 through 4
was 1.77 [95% CI 0.81, 3.87].
In considering combinations of exposures, we
focused on the period LM 2 through 4, when elevated
aORs were most apparent. During this period, only
the higher level of alcohol or coffee drinking conferred increased risks, whereas any smoking was
associated with at least a doubling in clubfoot
risk. Thus, the combinations of any smoking and >3
alcohol drinks/drinking day and any smoking and >3
coffee drinks/drinking day were examined. No case

M. M. Werler et al.

Table 2. Maternal cigarette, alcohol, and coffee use in early pregnancy in relation to isolated clubfoot
Cases n = 646
Exposure
Cigarette smoking
Anytime LM 24
10/day
>10/day
LM 2 quitters
10/day
>10/day
LM 3 quitters
10/day
>10/day
LM 2 through 4
10/day
>10/day
Alcohol
Anytime LM 24
3/day
>3/day
LM 2 quitters
3/day
>3/day
LM 3 quitters
3/day
>3/day
LM 2 through 4
3/day
>3/day
Coffee
Anytime LM 24
3/day
>3/day
LM 2 quitters
3/day
>3/day
LM 3 quitters
3/day
>3/day
LM 2 through 4
3/day
>3/day

Controls n = 2037

No.

No.

Unadjusted
odds ratio

95% CIa

aOR

95% CIb

154
33

23.8
5.1

326
63

16.0
3.1

1.70
1.88

[1.36, 2.11]
[1.22, 2.90]

1.73
2.13

[1.37, 2.21]
[1.33, 3.41]

52
17

8.0
2.6

133
37

6.5
1.8

1.40
1.65

[1.00, 1.96]
[0.92, 2.95]

1.35
1.62

[0.94, 1.95]
[0.86, 3.05]

5
5

0.8
0.8

25
15

1.2
0.7

0.72
1.19

[0.27, 1.88]
[0.43, 3.30]

0.89
1.27

[0.32, 2.45]
[0.43, 3.75]

86
21

13.3
3.3

150
29

7.4
1.4

2.05
2.59

[1.55, 2.73]
[1.47, 4.59]

2.21
2.58

[1.61, 3.02]
[1.38, 4.81]

56
36

8.7
5.6

145
67

7.1
3.3

1.27
1.77

[0.92, 1.76]
[1.17, 2.68]

1.09
1.25

[0.77, 1.54]
[0.80, 1.95]

51
30

7.9
4.6

115
54

5.6
2.7

1.46
1.83

[1.04, 2.06]
[1.16, 2.89]

1.35
1.30

[0.94, 1.96]
[0.79, 2.14]

1
1

0.2
0.2

11
7

0.5
0.3

0.30
0.47

[0.04, 2.33]
[0.06, 3.83]

0.24
0.36

[0.03, 1.96]
[0.04, 3.12]

4
5

0.6
0.8

19
6

0.9
0.3

0.69
2.75

[0.24, 2.05]
[0.84, 9.03]

0.54
2.38

[0.17, 1.65]
[0.66, 8.52]

110
34

17.0
5.3

330
78

16.2
3.8

1.12
1.25

[0.89, 1.41]
[0.80, 1.98]

0.93
0.96

[0.72, 1.19]
[0.58, 1.58]

29
11

4.5
1.7

89
44

4.4
2.2

1.06
0.81

[0.69, 1.63]
[0.42, 1.58]

0.85
0.66

[0.54, 1.36]
[0.32, 1.36]

3
2

0.5
0.3

17
6

0.8
0.3

0.57
1.08

[0.17, 1.96]
[0.22, 5.37]

0.63
0.71

[0.17, 2.29]
[0.13, 3.91]

84
14

13.0
2.2

234
20

11.5
1.0

1.16
2.27

[0.89, 1.52]
[1.14, 4.52]

0.98
1.77

[0.73, 1.30]
[0.81, 3.87]

Unadjusted.
Adjusted for all exposures, study centre, child sex, and maternal race/ethnicity, primiparity, obesity, fertility treatment, and LM 24
uses of opioids, selective serotonin reuptake inhibitor, phenergan, ondansetron, pseudoephedrine, diphenhydramine, amoxicillin, and
salicylates.

mothers reported both high alcohol and coffee drinking. The mothers of three cases and four controls
smoked and drank >3 alcohol drinks/drinking day
throughout LM 2 to 4, producing an aOR = 3.97 [95%
CI 0.82, 19.21]. However, there was no evidence of

synergism; the combined effect was not additively

greater than the individual effects of each exposure.
The mothers of 11 cases and 10 controls smoked and
drank >3 coffee drinks/drinking day; the aOR was
5.02 [95% CI 2.00, 12.55]. Synergism between cigarette
2014 John Wiley & Sons Ltd
Paediatric and Perinatal Epidemiology, 2015, 29, 310

Cigarettes, alcohol, coffee, and clubfoot

smoking and high-level coffee intake was suggested
(relative excess risk due to interaction = 2.62), but the
95% CI included the null [2.26, 7.50].
When analyses were restricted to the 570 cases and
2022 controls without a first degree family history of
clubfoot, aORs changed <10% with one exception. The
aOR for >3 alcohol drinks/drinking day LM 2
through 4 increased further to 3.01 [95% CI 0.84,
10.79].

Comment
Our findings confirm results of previous studies
showing cigarette smoking in pregnancy increases
clubfoot risk in offspring, and provide new evidence
that this risk is not confined to women who choose to
continue smoking after pregnancy is recognised.
Women who continued to smoke during the 3 months
after pregnancy is recognisable had more than a
twofold increased clubfoot risk, while women who
entered pregnancy as smokers and quit after a first
missed menstrual period had a 1.35-fold in clubfoot
risk, with a lower 95% confidence bound of 0.94.
Although risk estimates included the null value of 1.0,
our findings also suggest that consistent high-level
intake of alcohol or coffee in early pregnancy
increases the risk of clubfoot, particularly in combination with cigarette smoking. While there was no evidence of increased clubfoot risk for women who quit
drinking coffee the month after a first missed menstrual period, alcohol drinkers who did quit appeared
to have an approximate 33% increase in risk.
Of the 15 published studies that examined cigarette
smoking in pregnancy in relation to clubfoot,1115 12
reported elevated odds ratio estimates. None of these
studies reported on the timing of cigarette smoking in
pregnancy in relation to clubfoot risk.
Far fewer studies have examined maternal
alcohol2124 and coffee drinking22 in relation to clubfoot
risk. One of these studies was a series of 43 cases
(without a comparison group) and noted that three
mothers reported extremely high levels of alcohol
intake during pregnancy.24 Two studies did not
provide details on how information on alcohol was
collected, and all reported no association between any
alcohol consumption in pregnancy and clubfoot
risk.21,23 The one longitudinal study that examined
levels of alcohol and coffee exposures in the first trimester found neither was associated with clubfoot,25
nor was cigarette smoking, in contrast to other studies.
2014 John Wiley & Sons Ltd
Paediatric and Perinatal Epidemiology, 2015, 29, 310

Thus, the present analysis is the first to estimate

clubfoot risks by level and timing of cigarette smoke
exposure. Indeed, our data showed that both aspects
of exposure are relevant for identifying increased
clubfoot risks. For all three exposures, elevated risks
were most apparent for high-level exposures that are
continued after pregnancy is recognisable. However,
we also observed slightly elevated risk estimates for
women who quit smoking or drinking alcohol in the
second LM, which indicates women should not wait
until they know they are pregnant to quit these exposures; rather, these exposures during the early days of
gestation are compatible with sonogram evidence that
clubfoot develops early in gestation.
Cigarette smoke, alcoholic beverages, and coffee are
complex exposures, each with a mixture of components and by-products that might affect foot development in early gestation. The nicotine component of
cigarettes causes vasoconstriction in the mother and
the fetus,26 and it has been suggested that the pathogenesis of clubfoot includes vascular disruption.27
High levels of alcohol intake adversely affect blood
vessels in adults, including pregnant women.28 Caffeine exposure affects blood flow as an adenosine
antagonist.29 Thus, cigarette smoking, alcohol intake,
and coffee consumption might each influence foot
development via vascular disruption. Animal experiments show caffeine or xanthine can affect limb
development, and one study observed slightly
elevated odds ratios in relation to transverse limb deficiencies and three or more cups of coffee per day.30
Interestingly, the transverse subtype of limb deficiencies is purported to also have a vascular disruption
aetiology.27 High-intensity alcohol intake during pregnancy is associated with a constellation of structural
and developmental defects in offspring, but isolated
clubfoot is not considered a fetal alcohol effect. In
animal models, alcohol exposure has been shown to
amplify cell death, to contribute to the formation of
free radicals, and to interfere with folate metabolism;31,32 thus, its teratogenic effects may act through
any of these mechanisms. In the present analysis, the
association between high-level alcohol intake and
clubfoot risk was present among women who did and
who did not take folic acid supplements in the first
trimester; aORs were 2.46 based on three exposed
cases and 1.84 based on two exposed cases, respectively. Most of the focus of alcohol teratogenesis in
basic research is on the central nervous system.32
Although abnormal neurulation is present in clubfoot,

M. M. Werler et al.

it is not clear if the abnormalities are secondary to,

part of, or a causal factor in abnormal foot development. Peripheral nervous system anomalies, such as
those resulting from spina bifida, are associated with
clubfoot. Animal and human data are lacking on
whether either the central or peripheral nervous
systems play a role in the development of clubfoot.
The observed interaction for the, albeit rare, combination of cigarette smoking and high levels of coffee
drinking in relation to clubfoot raises the question of a
biological synergistic effect. Whereas nicotine and caffeine affect vasoactivity, they are also neuroactive, by
stimulating and/or suppressing neurotransmitters.33,34
Indeed, synergistic effects of nicotine and caffeine
exposures on neural functions have been observed.35,36
We previously reported a higher risk of clubfoot in
association with maternal use of selective serotonin
reuptake inhibitors in early pregnancy in two separate
studies37,38 (one being the present study).37 This line of
observations prompts us to speculate that the central
nervous system may have a role in clubfoot development. Its pathogenesis is undoubtedly complex, given
the high recurrence within families,37 predisposition
among boys and first births,19 association with in utero
exposure to cigarette smoke, and possible associations
with selective serotonin reuptake inhibitors,37,38 and
high-dose alcohol and coffee intakes. Thus, the
present findings do not clearly point towards any one
pathogenetic process for clubfoot development. A distinct advantage of the present study was its detailed
data on the amount and timing of cigarette, alcohol,
and coffee exposures, and many other known and
suspected risk factors for clubfoot. Thus, timing and
intensity of exposure were simultaneously explored,
and potential confounding was rigorously assessed.
We did not present results on how often women
drank alcohol, although we observed no elevated ORs
for clubfoot. All data were collected retrospectively,
raising the possibility of random or differential
misclassification. Women who report smoking or
alcohol drinking throughout early pregnancy are
likely exposed, but women who report little or no
such use may not be unexposed. If mothers of cases
are more likely to deny true exposures, the observed
odds ratios would be underestimates of the truth.
Another strength of this study was inclusion of
population-based, orthopaedist-confirmed cases and
controls from the population that gave rise to the
cases. However, not all women who were eligible
agreed to be interviewed. If women who did not par-

ticipate smoked, drank alcohol, or consumed coffee

more or less than women who did participate, and
the differences varied by case/control status, a bias
could result. For example, if case mothers who did
not participate were more likely to drink alcohol than
control mothers who did not participate, the observed
odds ratio would be underestimated. This scenario is
certainly possible, since public health advisories
against alcohol drinking in pregnancy have made this
behaviour socially unacceptable, and women with
affected infants who drank in pregnancy may therefore decline to participate. Only liveborn subjects
were included in the study. If the exposures under
study were positively associated with loss of isolated
clubfoot-affected fetuses, odds ratio estimates would
be biased downward. An additional limitation is that
the numbers of women in time- and level-specific
exposure categories were small for some comparisons. This was particularly true of quitters in LM 3 for
all three exposures. The resulting odds ratios were
unstable and do not reliably measure whether quitting in that second month after a missed menstrual
period ameliorates risk. Intake of caffeine from other
sources and passive smoke exposure were not considered. While coffee drinking and direct cigarette
smoking correspond to higher levels of caffeine and
nicotine exposures, women in the unexposed comparison groups might be exposed to these other
sources of exposure, which could produce a downward bias of true effects. It is possible that the
observed associations are due to uncontrolled confounding. Further, exposures in the periconceptional
period were not evaluated in this analysis; if a carryover effect on clubfoot risk exists, our inclusion of
such exposures in the reference group would also
produce a downward bias of odds ratios.
In summary, the present study found clear evidence
that maternal cigarette smoking through early
pregnancy increased the risk of clubfoot, even after
controlling for important confounding factors. Specifically, clubfoot risk appears to be increased for offspring of women who smoke cigarettes before they
become pregnant, and either quit after pregnancy is
clinically recognisable or continue smoking through
the next 3 months. Women who consumed throughout early pregnancy an average of more than three
servings of coffee per day or more than three alcohol
drinks on the days they drank may also have an
increased clubfoot risk in offspring, but associations
were less stable.
2014 John Wiley & Sons Ltd
Paediatric and Perinatal Epidemiology, 2015, 29, 310

Cigarettes, alcohol, coffee, and clubfoot

Acknowledgements
Support for this work was provided by Eunice
Kennedy Shriver National Institute for Child Health
and Human Development Grant RO1-HD051804. We
thank Lisa Crowell RN and Mary Beth Pender RN,
interviewers; Michelle Heinz and Eileen Mack,
research assistants; Michael Bairos, Oleg Starobinets,
and Elie Sirotta, database analysts; Katherine E Kelley,
MPH, RPh; and the mothers who participated in the
study.

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