State Center for Health Statistics Statistical Brief No. 31 – March 2007
N. C. Department of Health and Human Services 1 Division of Public Health
Maternal Smoking During Pregnancy
and the Risk for Clubfoot in Infants: North Carolina, 1999- 2003
by Kathryn C. Dickinson, Robert E. Meyer, and Jonathan B. Kotch*
Statistical Brief No. 31
North Carolina
Department of Health and Human Services
Division of Public Health
State Center for Health Statistics March 2007
Statistical
Brief
www. schs. state. nc. us/ SCHS/
* Kathryn Dickinson and Robert Meyer are with the North
Carolina Birth Defects Monitoring Program, State Center for
Health Statistics. Jonathan Kotch is with the Department of
Maternal and Child Health, UNC School of Public Health.
Introduction
Talipes equinovarus, or clubfoot, is one of the
most common major birth defects, with a preva-lence
of approximately 1 per 1,000 live births. 1- 3
Clubfoot affects males about twice as often as
females. 4- 5 Infants born with clubfoot have
abnormal foot bones, ankle bones, foot muscles
and ligaments, and their heel cords are often tight,
preventing the development of a normal gait.
These malformations require medical treatment
and often surgery for correction.
The causes of clubfoot are not well understood,
although many have been proposed. A partial list
of these causes include: intrauterine compression,
vascular insufficiency, and neurologic abnormali-ties.
6- 8 Genetic and environmental factors are
thought to play a role as well. 9- 10 Maternal smok-ing
during pregnancy is one environmental risk
factor that has been studied with varying results,
with findings ranging from a positively- correlated
dose- response effect to a protective effect. 11- 12
This population- based case- control study aimed to
further explore the link between maternal smok-ing
during pregnancy and clubfoot in infants. It
was hypothesized that maternal smoking during
pregnancy would be associated with an increased
risk of clubfoot being present in infants.
Methods
This study used data from the North Carolina
Birth Defects Monitoring Program ( NCBDMP)
matched to the Composite Linked Birth File. The
Composite Linked Birth File contains all North
Carolina resident birth certificates linked to
Medicaid paid claims and health department
service data, such as the Special Supplemental
Nutrition Program for Women, Infants, and
Children ( WIC) and maternity care coordination.
Infants born in 1999- 2003 and diagnosed with
clubfoot were ascertained by the NCBDMP.
Cases included live- born, singleton infants with a
diagnosis of either isolated ( non- syndromic)
talipes equinovarus or clubfoot not otherwise
specified ( British Pediatric Association codes
754.500 and 754.730). Non- isolated cases, which
were excluded from the analysis, were those
where there was also a major congenital anomaly
in another organ system, or another major muscu-loskeletal
defect not related to clubfoot, such as a
limb reduction defect. After excluding the non-isolated
cases ( about 35%) and those with missing
maternal smoking data, a total of 443 cases were
eligible for the study.
Statistical Brief No. 31 – March 2007 State Center for Health Statistics
N. C. Department of Health and Human Services 2 Division of Public Health
Controls were obtained from North
Carolina birth certificates and verified
against the NCBDMP database to
exclude infants with major birth
defects. A simple random sample of
4,500 singleton births from the years
1999- 2003 was generated. After
excluding records with missing smok-ing
data, there were 4,492 controls
eligible for the study.
Smoking status was ascertained from
the birth certificate ( yes/ no). In order
to assess the reliability of smoking data
on the birth certificate, North Carolina
Pregnancy Risk Assessment Monitor-ing
System ( PRAMS) survey data on
self- reported maternal smoking were
compared to smoking status as re-ported
on the birth certificate for each
PRAMS respondent for the years 1999-
2003.
Other variables included in the analysis
were maternal age, race/ ethnicity,
marital status, maternal education,
parity ( number of previous live births),
Medicaid and WIC status, timing of
prenatal care initiation, infant’s sex,
gestational age, birth weight, and infant
death. Frequencies, unadjusted odds
ratios, and adjusted odds ratios ( using
binary logistic regression) were com-puted.
Results
Comparing self- reported maternal
smoking from PRAMS with smoking
status as reported on the birth certifi-cates
for 1999- 2003 indicated good
agreement between the two sources.
Approximately 95 percent of the
8,157 records were in concurrence
( Kappa= 0.769).
Table 1 shows the descriptive statis-tics
for both cases and controls. Case
mothers were more likely to have
Table 1. Characteristics of case mothers and infants
versus controls, North Carolina, 1999- 2003
Cases Controls
n= 443 n= 4,492
number (%)* number (%)*
Maternal smoking
Yes 81 ( 18.3) 587 ( 13.1)
No 362 ( 81.7) 3905 ( 86.9)
Infant’s sex
Male 291 ( 65.7) 2272 ( 50.6)
Female 152 ( 34.3) 2220 ( 49.4)
Maternal age
< 20 61 ( 13.8) 501 ( 11.2)
20- 24 137 ( 30.7) 1258 ( 28.0)
25- 29 122 ( 27.5) 1223 ( 27.3)
> 30 124 ( 28.0) 1510 ( 33.6)
Maternal race/ ethnicity
White, non- Hispanic 302 ( 68.2) 2728 ( 60.7)
Black, non- Hispanic 81 ( 18.3) 1075 ( 23.9)
Hispanic 49 ( 11.1) 527 ( 11.7)
Other 11 ( 2.5) 162 ( 3.6)
Maternal education
< High School 106 ( 23.9) 989 ( 22.0)
High School 144 ( 32.5) 1420 ( 31.6)
> High School 187 ( 42.2) 2068 ( 46.0)
Marital status
Married 283 ( 63.9) 2996 ( 66.7)
Unmarried 160 ( 36.1) 1495 ( 33.3)
Parity
0 239 ( 54.0) 1802 ( 40.1)
1- 3 194 ( 43.8) 2551 ( 56.8)
> 3 10 ( 2.3) 138 ( 3.1)
Gestational age ( in weeks)
< 32 10 ( 2.3) 83 ( 1.8)
33- 36 56 ( 12.6) 324 ( 7.2)
> 37 377 ( 85.1) 4085 ( 90.9)
Receipt of WIC
Yes 197 ( 45.5) 1674 ( 37.3)
No 246 ( 55.5) 2818 ( 62.7)
Receipt of Medicaid
Yes 100 ( 45.1) 1792 ( 39.9)
No 243 ( 54.9) 2700 ( 60.1)
Timing of prenatal care initiation
Adequate ( 1st trimester) 415 ( 93.7) 4057 ( 90.3)
Late ( after 1st trimester or none) 25 ( 5.6) 414 ( 9.2)
Infant death
Yes 2 ( 0.5) 29 ( 0.6)
No 441 ( 99.5) 4463 ( 99.4)
* Percents may not add to 100 due to missing values.
State Center for Health Statistics Statistical Brief No. 31 – March 2007
N. C. Department of Health and Human Services 3 Division of Public Health
smoked during pregnancy, with 18.3 percent
reporting they did so compared to 13.1 percent of
control mothers. Case infants were more likely to
be male than control infants ( 65.7% vs. 50.6%).
Control mothers were less likely to be non-
Hispanic white and also less likely to be primipa-rous
compared to case mothers. Examining the
relationship between smoking and clubfoot
indicated that women who smoked during preg-nancy
were about 50 percent more likely to
deliver an infant with clubfoot compared to
women who did not smoke ( unadjusted odds ratio
( OR) = 1.49; 95% confidence interval ( CI) = 1.15-
1.92). After adjusting for sex of the infant,
maternal age, race/ ethnicity, and the timing of
prenatal care initiation, the odds ratio did not
change appreciably ( adjusted OR = 1.40, 95% CI
= 1.07- 1.83) ( Table 2). Also shown in Table 2,
male infants were almost twice as likely to have
clubfoot than female infants, increasing maternal
age was associated with a slightly reduced risk of
having a baby with clubfoot, and non- Hispanic
black women were about one- third less likely to
have a baby with clubfoot than their non- Hispanic
white counterparts.
Table 2. Adjusted odds ratios ( OR) and
95% confidence intervals ( CI) for the
association of clubfoot and maternal
smoking during pregnancy,
North Carolina, 1999- 2003
OR ( 95% CI)
Maternal Smoking
Yes 1.40 ( 1.07, 1.83)
No 1.00
Infant’s Sex
Male 1.89 ( 1.54, 2.32)
Female 1.00
Maternal age ( continuous) 0.97 ( 0.95, 0.99)
Maternal race/ ethnicity
White, non- Hispanic 1.00
Black, non- Hispanic 0.67 ( 0.51, 0.87)
Hispanic 0.91 ( 0.65, 1.27)
Other 0.66 ( 0.35, 1.23)
Timing of prenatal care initiation
Adequate ( 1st trimester) 1.00
Late ( after 1st trimester or none) 0.70 ( 0.51, 0.96)
Conclusions
The findings of this study are consistent with the
hypothesis that maternal smoking during preg-nancy
confers an increased risk of an infant being
born with clubfoot. More research is necessary to
elucidate the biologic mechanisms by which
maternal smoking affects a developing fetus, and
the combined role that genetics and environment
play in this process. This study, in conjunction
with the results of previous investigations, under-scores
the need to educate women of childbearing
age of the array of adverse outcomes that may
affect the infant whose mother smokes during
pregnancy. These include birth defects as well as
low birth weight and sudden infant death syn-drome
( SIDS).
References
1. Wynne- Davies R. 1964. Family studies and the
cause of congenital clubfoot. J Bone Joint Surg
Am 46: 445- 452.
2. Ching GH, Chung CS, Nemecheck RW. 1969.
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Hum Genet 21: 566- 580.
3. Moorthi RN, Hashmi SS, Langois P, Canfield M,
Waller DK, Hecht JT. 2005. Idiopathic talipes
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Med Genet 132A: 376- 380.
4. Alberman ED. 1965. The causes of congenital
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5. Cartlidge I. 1984. Observations on the epidemiol-ogy
of clubfoot in Polynesian and Caucasian
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6. Kite JH. Etiology of clubfoot. 1964. In: Kite JH,
editor. The clubfoot. New York: Grune &
Stratton. p. 3- 12.
7. Hootnick DR, Packard DR, Levinsohn EM,
Wladis A. 1994. A vascular hypothesis for the
etiology of clubfoot. In: The clubfoot. New York:
Springer- Verlag.
8. Martin RF, Milo- Manson G, McComas A, Levin
S. 1994. Neurogenic origin of talipes
equinovarus. In: Simon G, editor. The clubfoot:
the present and a view of the future. New York:
Springer- Verlag. 39- 41.
9. Honein MA, Paulozzi LJ, Moore CA. 2000.
Family history, maternal smoking, and clubfoot:
Statistical Brief No. 31 – March 2007 State Center for Health Statistics
N. C. Department of Health and Human Services 4 Division of Public Health
400 copies of this public document were printed at a cost of $ 72.51 or 18¢ per copy. 3/ 07 Printed on recycled paper
State of North Carolina
Michael F. Easley, Governor
Department of Health and Human Services
Carmen Hooker Odom, Secretary
Division of Public Health
Leah Devlin, DDS, Director
Chronic Disease and Injury Section
Marcus Plescia, M. D., M. P. H., Section Chief
State Center for Health Statistics
Paul A. Buescher, PhD, Director
www. ncdhhs. gov
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Department of Health and Human Services
State Center for Health Statistics
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Raleigh, NC 27699- 1908
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For more information about this
publication, contact:
Kathryn Dickinson at ( 919) 715- 0263
e- mail: Kathryn. Dickinson@ ncmail. net
For a list of other publications by the
State Center for Health Statistics call:
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or check the website at:
www. schs. state. nc. us/ SCHS/
an indication of a gene- environment interaction.
Am J Epidemiol 152: 658- 665.
10. Wynne- Davies R. 1972. Genetic and environ-mental
factors in the etiology of talipes
equinovarus. Clin Orthop 84: 9- 13.
11. Skelly AC, Holt VL, Mosca VS, Alderman BW.
2002. Talipes equinovarus and maternal smoking:
a population- based case- control study in Wash-ington
state. Teratology 66: 91- 100.
12. Shiono PH, Klebanoff MA, Berendes HW. 1986.
Congenital malformations and maternal smoking
during pregnancy. Teratology 34: 65- 71.