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Maternal smoking during pregnancy and rapid weight gain from birth to early infancy
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Title, study in review, study context, study objective, type of study and population, analysis of data, results, potential biases, limitations, generalizations, possible future studies, public health practices, conclusion
Original Article
Maternal smoking during pregnancy and rapid weight gain from birth
to early infancy
Tomosa Mine a
, Taichiro Tanaka a, *
, Tadashi Nakasone b
, Toru Itokazu c
,
Zentaro Yamagata d
, Yuji Nishiwaki a
a Department of Environmental and Occupational Health, School of Medicine, Toho University, Tokyo, Japan
b Department of Public Health and Medical Care, Hokubu Regional Public Health Center, Okinawa Prefectural Government, Naha, Japan
c Department of Public Health and Medical Care, Health and Longevity Division, Okinawa Prefectural Government, Naha, Japan
d Department of Health Sciences, Basic Science for Clinical Medicine, Division of Medicine, Graduate School Department of Interdisciplinary Research,
University of Yamanashi, Chuo, Yamanashi, Japan
article info
Article history:
Received 24 December 2015
Accepted 19 April 2016
Available online 3 December 2016
Keywords:
Rapid weight gain
Pregnancy
Smoking
abstract
Background: Although several studies have focused on the association between maternal smoking
during pregnancy and rapid weight gain (RWG) during infancy, the dose-response relationship has not
yet been confirmed, and very few studies have included Asian populations. Using a record-linkage
method, we examined the association between maternal smoking during pregnancy and RWG in infants
at around 4 months of age to clarify the dose-response relationship.
Methods: Two databases were used: maternal check-ups during pregnancy and early infancy check-ups
(between April 1, 2013 and March 31, 2014 in Okinawa, Japan) were linked via IDs and provided to us
after unlinkable anonymizing. For 10,433 subjects (5229 boys and 5204 girls), we calculated the change
in infants’ weight z-score by subtracting the z-score of their birth weight from their weight at early
infancy check-ups. Smoking exposure was categorized into five groups. We used Poisson regression to
examine the association of maternal smoking during pregnancy with RWG in early infancy.
Results: Overall, 1524 (14.6%) were ex-smoker and 511 (4.9%) were current smoker. Compared with the
reference category of non-smokers, the adjusted risk ratio of RWG was 1.18 (95% confidence interval [CI],
1.06e1.32) for ex-smokers, 1.18 (95% CI, 0.93e1.50) for those who smoked 1e5 cigarettes per day, 1.57
(95% CI, 1.24e2.00) for those who smoked 6e10 cigarettes per day, and 2.13 (95% CI, 1.51e3.01) for those
who smoked 11 cigarettes per day. There was a clear dose-response relationship.
Conclusion: Our study suggests that maternal smoking during pregnancy is associated in a dosedependent
manner with increased risk of RWG in early infancy.
© 2016 The Authors. Publishing services by Elsevier B.V. on behalf of The Japan Epidemiological
Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).
1. Introduction
Maternal smoking during pregnancy is known to restrict intrauterine
growth, leading to low birth weight. Studies have also
indicated that maternal smoking during pregnancy can lead to
overweight or obesity in infancy and childhood,1e4 and that rapid
weight gain (RWG) in early infancy can increase the risk of cardiovascular
disease and type 2 diabetes in early adulthood.5,6 Ong
et al. have shown an association between RWG during the first 2
years of life and subsequent obesity, suggesting that this 2-year
postnatal period is an important opportunity to prevent the later
development of obesity and metabolic disease.7
Several studies have focused on the association of maternal
smoking during pregnancy and RWG during infancy.8e10 However,
the dose-response relationship, which is important for inferring a
causal relationship, has not yet been confirmed. Second, very few
recent studies have included Asian populations. Japanese women
generally have lower BMI, lower gestational weight gain, and
offspring with lower birth weight than Western women11e14; they
also tend to smoke less. The association between maternal smoking
during pregnancy and RWG would be strengthened if it were also
* Corresponding author. Department of Environmental and Occupational Health,
School of Medicine, Toho University, 5-21-16, Omori-Nishi, Ota-ku, Tokyo, 143-
8540, Japan.
E-mail address: taichirou.tanaka@med.toho-u.ac.jp (T. Tanaka).
Peer review under responsibility of the Japan Epidemiological Association.
Contents lists available at ScienceDirect
Journal of Epidemiology
journal homepage: http://www.journals.elsevier.com/journal-of-epidemiology/
http://dx.doi.org/10.1016/j.je.2016.10.005
0917-5040/© 2016 The Authors. Publishing services by Elsevier B.V. on behalf of The Japan Epidemiological Association. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Journal of Epidemiology 27 (2017) 112e116
observed in a Japanese population. Moreover, low birth weight is
known to be an independent risk factor for RWG within the first 2
years of life.7 Therefore, our study tried to assess the direct effect of
maternal smoking on RWG in early infancy in a population without
low birth weight.
Health check-ups are provided free of charge in Japan for infants
at around 4 months of age, and almost all Japanese infants receive
them. We can use the unique resulting dataset to investigate the
association between maternal smoking and RWG in early infancy in
a community setting via cross-referencing with data collected on
the mothers at check-ups during pregnancy. Obtaining data during
early infancy also helps minimize the effects of lifestyle factors,
such as patterns of movement (e.g., crawling and standing), diet,
and sleep habits.
The purpose of this study was to use a record-linkage method to
examine the association of maternal smoking during pregnancy
with RWG in infants at around 4 months of age and to clarify the
dose-response relationship.
2. Methods
2.1. Study subjects
All 41 municipalities in Okinawa prefecture provide to free four
check-ups for pregnant women and infants (at early and late infancy,
18 months, and 36 months) using the same standardized
questionnaire. Pregnant women received maternal health checkups
at a medical institute, with questionnaires distributed at municipalities’
health centers. Infants received infant check-ups, with
questionnaire mailed to each family from municipalities’ health
centers.
Two databases were used for this study, one including data
collected on mothers at check-ups during pregnancy (maternal
check-ups) and the other including information on infants
receiving check-ups at around 4 months of age (early infancy checkups).
Okinawa Prefecture collected data of both check-ups from 41
municipalities and linked data cross-referenced via IDs in maternity
record books. Data were provided to us after unlinkable anonymizing.
Between April 1, 2013 and March 31, 2014, 15,781 (91.6%)
of the 17,229 infants entitled to early infancy check-ups in Okinawa
Prefecture received them. After the linkage to the maternal checkup
database, 12,373 subjects (6162 boys and 6211 girls) were
singleton and had complete data at the first (around 8e11 weeks of
gestation) and the last (around 34e37 weeks of gestation) maternal
check-ups. Further, we excluded 1940 subjects falling into one or
more of the following categories: preterm gestational age <37
weeks (n ¼ 443), birth weight <2500 g (n ¼ 695) or 4000 g
(n ¼ 79), no information about maternal smoking status durin
g
pregnancy or anthropometric data (n ¼ 303), and age at check-ups
<3 months or >5 months (n ¼ 420). Analyses were carried out on
the remaining 10,433 subjects (5229 boys and 5204 girls).
2.2. Information on maternal smoking during pregnancy
The mothers were asked about maternal smoking status during
pregnancy using a self-reported questionnaire at their first
maternal check-ups. This questionnaire included questions about
their smoking status before and during pregnancy (current or not)
and the number of cigarettes they smoked per day. Those mothers
who had smoked before but not during pregnancy were classified
as ex-smokers. Current smokers during pregnancy were classified
according to the number of cigarettes smoked daily, in multiples of
five: 1e5, 6e10, and 11 cigarettes per day (there were only three
groups because few subjects smoked 16 cigarettes per day).
2.3. Rapid weight gain
Data on the subjects’ weight in early infancy (age 3e5 months)
were collected at the early infancy check-ups. Data on the subjects’
birthweight and gestational age were transcribed from maternal
record books by nurses or public health nurses at the same checkups.
We calculated weight z-score (observed value e mean/standard
deviation [SD]) at birth. Calculating weight z-score at birth,
Ong et al. adjusted for gestational age and sex,7 and Project Koshu
adjusted only for sex, without adjusting for gestational age.15 We
used the latter method, though both gave us a similar results in this
study. We calculated weight z-score at early infancy according to
sex and month of age. The mean and SD were based on the available
data on all of the infants receiving early infancy check-ups in the
study period (n ¼ 15,781), according to Project Koshu.15 The weight
distribution in our data was similar to that found in Japan’s 2000
survey on growth of infants and preschool children16 and was not
skewed, so we calculated direct z-scores. RWG in early infancy was
assessed on the basis of changes in weight z-score from birth to
early infancy, with a change exceeding þ0.67 defined as RWG.
According to Ong et al., a z-score of 0.67 represent the width of each
percentile band on standard growth charts (2nd, 10th, 25th, 50th,
75th, 90th, and 98th percentile lines); thus, a weight gain
exceeding þ0.67 SD indicates an increase across at least one of
these percentile bands.7
2.4. Covariates
Information was collected at the maternal check-ups on age,
pre-pregnancy body mass index (BMI; weight [kg]/length [m]2
),
and weight gain during pregnancy (subtracting the pre-pregnancy
weight from the weight at the last maternal check-up). At the early
infancy check-ups, information was collected on sex, gestational
age at birth, birth order, birth weight, and paternal smoking during
pregnancy. We also collected information on how the infants had
been fed between birth and the early infancy check-ups and divided
them into three feeding categories: exclusive breast-feeding, mixed
feeding, and exclusive bottle-feeding.
2.5. Statistical analysis
We used Stata 12 for Windows (STATA Corporation, College
Station, TX, USA) software for statistical analysis, and we used
Poisson regression analysis to estimate crude and adjusted risk
ratios (RRs) and 95% confidence intervals (CIs) for RWG during early
infancy according to maternal smoking status during pregnancy.
We found no statistical interaction according to infant sex
(p ¼ 0.44), so we constructed combined models for both sexes. Our
multivariable model included potential confounders identified in
previous studies: infants’ sex, birth order (first, second, or later),
maternal age (26 years [25th percentile], 27e33 years [25th-75th
percentile], or 34 years [75th percentile]), paternal smoking
during pregnancy (current or not), gestational age (continuous),
and maternal pre-pregnancy BMI (<18.5, 18.5e22.9, 23e24.9, or
25 kg/m2
). The inclusion of age in days from birth to infancy
check-ups in the multivariable model did not alter the results
substantially, so we did not adopt this factor as a covariate. This
multivariable model was further adjusted individually for type of
feeding between birth and the early infancy check-ups (exclusive
breast-feeding, mixed feeding, or exclusive bottle-feeding),
maternal weight gain (<5, 5e6.9, 7e8.9, 9e10.9, 11e12.9, or
13 kg), and birth weight (continuous). A previous study had found
interaction between maternal smoking and type of feeding between
birth and early infancy check-ups in the risk of RWG,17 but
we found no interaction (p ¼ 0.39). Therefore, we treated feeding as
T. Mine et al. / Journal of Epidemiology 27 (2017) 112e116 113
a covariate. For trend analysis, Poisson regression analysis was
repeated, with smoking categories given integer values.
2.6. Ethical considerations
All data provided by Okinawa Prefecture were anonymized in an
unlinkable fashion, and the researchers were blinded to personal
information about the mothers and infants. This study was
approved by the Ethics Committee of Toho University (approval
number: 25124).
3. Results
Table 1 shows the maternal smoking status during pregnancy of
the study subjects. In total, 8398 (80.5%) were non-smokers, 1524
(14.6%) were ex-smokers, and 511 (4.9%) reported smoking during
pregnancy. A majority (52.8%) of the current smokers smoked 1e5
cigarettes per day. The current smokers tended to be younger, to be
overweight, to gain less weight during pregnancy, and to have
husbands who smoked during pregnancy. The infants whose
mothers smoked were likely to be second or later children and to
have received mixed feeding.
Table 2 shows the anthropometric data of the infants by sex and
maternal smoking status. In both sexes, average birth weight and zscore
at birth tended to decrease as the number of cigarettes
smoked by their mothers increased. In contrast, average weight and
z-score during early infancy tended to increase in line with the
number of cigarettes smoked by the mothers. Thus, changes in
weight z-score and the incidence of RWG in early infancy increased
in line with increased maternal smoking: around 20% of the infants
with non-smoking mothers experienced RWG, whereas the proportion
was almost 40% among infants whose mothers smoked 11
cigarettes per day.
Table 3 shows the dose-response relationship between the
smoking category (based on the number of cigarettes smoked by
mothers during pregnancy) and the risk of RWG in early infancy, as
determined by Poisson regression analysis. Compared with nonsmokers,
the multivariable-adjusted RRs for RWG were 1.18 (95%
CI, 1.06e1.32) for ex-smokers, 1.18 (95% CI, 0.93e1.50) for those who
smoked 1e5 cigarettes per day, 1.57 (95% CI, 1.24e2.00) for those
who smoked 6e10 cigarettes per day, and 2.13 (95% CI, 1.51e3.01)
for those who smoked 11 cigarettes per day. Further adjustment
for type of feeding between birth and early infancy, and for
maternal weight gain during pregnancy, did not change the RRs
substantially (Table 3). In contrast, adjustment for birth weight
attenuated the RRs, although a statistically significant association
between maternal smoking status and RWG remained. When
smoking categories were treated as integer values, upward trends
across smoking statuses were observed (p for trend<0.05 for each
model).
In order to minimize the influence of the difference in days
between birth and early infancy check-ups, we limited to infants
who received check-ups at 4 months of age and repeated the
analysis, with similar results (eTable 1).
4. Discussion
This study showed an increased risk of RWG in early infancy for
infants exposed to maternal smoking during pregnanc
y, and a clear
dose-response relationship was observed between the number of
Table 1
Characteristics of the study population by maternal smoking during pregnancy.
Current-smoker (number of cigarettes per day)
Non-smoker
(n ¼ 8398)
n (%)a
Ex-smoker
(n ¼ 1524)
n (%)a
1-5 cigarettes/day
(n ¼ 270)
n (%)a
6e10 cigarettes/day
(n ¼ 189)
n (%)a
11 cigarettes/day
(n ¼ 52)
n (%)a
p-valueb
Parental
Maternal age, years <0.001
26 (<25th percentile) 1820 (21.7) 645 (42.3) 122 (45.2) 64 (33.9) 12 (23.1)
27-33 (25-75th percentile) 3843 (45.8) 556 (36.5) 103 (38.2) 82 (43.4) 32 (61.5)
34 (>75th percentile) 2731 (32.5) 323 (21.2) 45 (16.7) 43 (22.8) 8 (15.4)
Maternal BMI <0.001
<18.5 kg/m 1240 (14.8) 239 (15.7) 53 (19.6) 24 (12.8) 7 (13.5)
18.5e22.9 kg/m 5266 (62.8) 865 (57.0) 139 (51.5) 102 (54.3) 22 (42.3)
23e24.9 kg/m 929 (11.1) 187 (12.3) 30 (11.1) 23 (12.2) 5 (9.6)
25 kg/m 947 (11.3) 228 (15.1) 48 (17.8) 29 (20.7) 18 (34.6)
Weight gain during pregnancy <0.001
4.9 kg 913 (10.9) 124 (8.1) 25 (9.2) 32 (14.9) 14 (26.7)
5e6.9 kg 1133 (13.5) 133 (8.7) 19 (7.0) 18 (9.5) 8 (15.4)
7e8.9 kg 2032 (24.2) 254 (16.7) 53 (19.6) 46 (24.3) 12 (23.1)
9e10.9 kg 2106 (25.1) 283 (18.6) 56 (20.7) 31 (16.4) 8 (15.4)
11e12.9 kg 1310 (15.6) 279 (18.3) 58 (21.5) 30 (15.9) 5 (9.6)
13 kg 904 (10.8) 451 (29.6) 59 (21.9) 32 (16.9) 5 (9.7)
Paternal smoking during pregnancy 2551 (33.1) 945 (64.2) 210 (80.2) 151 (83.0) 37 (74.0) <0.001
Infancy
Sex (boy) 4223 (50.3) 738 (48.4) 145 (53.7) 90 (47.6) 33 (64.5) 0.12
Gestational agec 39.0 (1.1) 39.1 (1.1) 39.1 (1.1) 39.0 (1.1) 38.8 (1.2) 0.18
Birth order <0.001
First 2913 (34.9) 720 (47.5) 119 (44.4) 52 (28.8) 15 (28.9)
Second or later 5430 (65.1) 796 (52.5) 149 (55.6) 131 (71.25) 37 (71.2)
Feeding between birth and early infancy checkups <0.001
Exclusive breast-feeding 3011 (36.1) 392 (25.9) 67 (25.0) 34 (18.2) 16 (31.4)
Mixed-feeding 2923 (35.0) 705 (46.7) 141 (52.6) 115 (61.5) 27 (53.0)
Exclusive bottled feeding 2419 (29.0) 414 (27.4) 60 (22.4) 38 (20.3) 8 (15.7)
BMI, body mass index.
Due to missing values, the totals for the stratified subgroups are not equal. a Column %. b p-value for c2 test or Analysis of variance or Fisher’s exact test. c Mean (standard deviation).
114 T. Mine et al. / Journal of Epidemiology 27 (2017) 112e116
cigarettes smoked and RWG risk. The association remained after we
adjusted for the type of feeding, maternal weight gain during
pregnancy, and birth weight, so our results suggest that the association
of maternal smoking status during pregnancy with RWG in
early infancy is independent of these three factors.
Previous studies on the association between maternal smoking
during pregnancy and weight gain in infancy have shown disparate
results, perhaps largely because of differences in the study
periods and outcome indicators.8,9,18 However, most studies
focusing on weight gain in early infancy have shown a positive
association between maternal smoking during pregnancy and
weight gain. In a cohort study of neonates carried out in Norway in
1992 and 1993, Nafstad et al. used weight gain during the first
year as an outcome indicator and found that infants born to
smoking mothers gained more weight, in a dose-dependent
manner, than those born to non-smoking mothers.9 They also
investigated breast-feeding during the first 6 months and suggested
that the observed weight gain could be partially explained
by the shorter duration of breast-feeding by smoking mothers. In
Canada, Dubois observed infants born in 1998 from birth to 5
months of age and found that those born to smoking mothers
gained more weight than those born to non-smoking mothers.18
Harrod et al. used air-displacement plethysmography to measure
changes in the body composition of infants born in the United
States between July 2010 and November 2013 from birth to 5
months.19 They found that fat-free mass at 5 months was signifi-
cantly greater in infants exposed to prenatal smoking than in
those not exposed, but that the mean change in weight-for-length
z-score of offspring between birth and 5 months was not signifi-
cantly different.
Two other studies20,21 investigated the association between
maternal smoking during pregnancy and RWG in infancy using the
same definition of RWG by Ong et al. used in our study. Wijlaars
et al. analyzed 2402 infant/parent pairs in England and reported a
positive association between maternal smoking during pregnancy
and RWG at 3 months of age.20 With non-smokers as the reference
category, the odds ratio (OR) of RWG in infants of mothers who
smoked during pregnancy was 1.34 (95% CI, 1.00e1.78). However,
they did not investigate the dose-response relationship. Lyte et al.
studied 11,134 children and parents in Ireland to investigate the
Table 2
Anthropometric data by sex and maternal smoking during pregnancy.
Current smoker
Non-smoker
Mean (SD)
Ex-smoker
Mean (SD)
1-5
cigarettes/day
Mean (SD)
6-10
cigarettes/day
Mean (SD)
11
cigarettes/day
Mean (SD)
Total (n ¼ 10,433) 8398 1524 270 189 52
Birth weight 3083.1 (317.4) 3076.1 (312.5) 3053.4 (298.6) 3014.9 (306.6) 2947.4 (251.3)
z-score at birth 0.21 (0.76) 0.20 (0.75) 0.14 (0.71) 0.05 (0.73) 0.11 (0.60)
Weight at early infancy 6960.7 (802.0) 7052.0 (823.9) 7048.1 (818.3) 7165.8 (921.8) 7147.8 (683.9)
z-score at early infancy 0.04 (0.94) 0.15 (0.96) 0.12 (0.97) 0.23 (1.07) 0.26 (0.84)
Change in weight z-score from birth to early infancy 0.17 (0.94) 0.05 (0.93) 0.02 (1.00) 0.18 (0.99) 0.38 (0.94)
Rapid weight gain (%) 1527 (18.8) 335 (22.0) 57 (21.1) 54 (28.6) 20 (38.5)
Boys (n ¼ 5229) 4223 738 145 90 33
Birth weight 3114.7 (315.2) 3109.3 (311.2) 3082.4 (316.5) 3067.0 (299.1) 2923.6 (207.8)
z-score at birth 0.19 (0.75) 0.18 (0.73) 0.12 (0.75) 0.09 (0.71) 0.26 (0.49)
Weight at early infancy 7208.8 (780.8) 7296.1 (801.3) 7213.8 (769.7) 7418.2 (882.6) 7276.5 (770.9)
z-score at early infancy 0.03 (0.94) 0.14 (0.97) 0.01 (0.95) 0.23 (1.06) 0.14 (0.93)
Change in weight z-score from birth to early infancy 0.16 (0.94) 0.04 (0.93) 0.12 (0.98) 0.14 (1.00) 0.41 (0.84)
Rapid weight gain (%) 783 (18.5) 166 (22.5) 25 (17.2) 24 (26.7) 13 (39.4)
Girls (n ¼ 5204) 4175 786 125 99 19
Birth weight 3051.2 (316.4) 3044.8 (310.6) 3019.9 (273.8) 2964.8 (306.3) 2988.6 (315.1)
z-score at birth 0.24 (0.77) 0.22 (0.76) 0.16 (0.66) 0.28 (0.75) 0.09 (0.76)
Weight at early infancy 6709.7 (743.0) 6822.9 (778.1) 6855.8 (833.9) 6936.3 (900.4) 6924.5 (431.0)
z-score at early infancy 0.06 (0.94) 0.20 (0.97) 0.25 (1.05) 0.29 (1.10) 0.26 (0.61)
Change in weight z-score from birth to early infancy 0.18 (0.95) 0.03 (1.09) 0.09 (1.09) 0.26 (1.03) 0.18 (1.03)
Rapid weight gain (%) 744 (17.8) 169 (21.5) 32 (25.6) 30 (30.3) 7 (36.8)
SD, standard deviation.
Table 3
Risk ratios of rapid weight gain at early infancy by maternal smoking during pregnancy, With calculated weight z-scores at birth adjusted for sex and gestational age.
Further adjusted by
n/N (%)
Crude
risk ratio
(95% CI)
Multivariable
risk ratioa
(95% CI)
Feeding between birth and
early infancy checkups
(95% CI)
Maternal weight gain
during pregnancy
(95% CI)
Birth weight
(95% CI)
Non-smoker 1527/8398 (18.2) ref ref ref ref ref
Ex-smoker 335/1524 (22.0) 1.21 (1.09e1.34) 1.18 (1.06e1.32) 1.18 (1.05e1.32) 1.19 (1.06e1.34) 1.17 (1.05e1.32)
Current-smoker 1e5 cigarettes/day 57/270 (21.1) 1.16 (0.91e1.47) 1.18 (0.93e1.50) 1.17 (0.92e1.48) 1.18 (0.93e1.51) 1.14 (0.89e1.44)
6e10 cigarettes/day 54/189 (28.6) 1.57 (1.25e1.98) 1.57 (1.24e2.00) 1.55 (1.22e1.98) 1.58 (1.24e2.01) 1.41 (1.10e1.80)
11 cigarettes/day 20/52 (38.5) 2.12 (1.50e2.99) 2.
13 (1.51e3.01) 2.05 (1.43e2.93) 2.13 (1.51e3.01) 1.80 (1.30e2.50)
Risk ratio for one category increase 1.17 (1.11e1.23) 1.15 (1.10e1.21) 1.16 (1.10e1.23) 1.16 (1.09e1.22) 1.13 (1.07e1.19)
CI, confidence interval. a Adjusted for infant’ sex, birth order, maternal age, paternal smoking during pregnancy, gestational age, and pre-pregnant BMI.
T. Mine et al. / Journal of Epidemiology 27 (2017) 112e116 115
risk of RWG at 9 months,21 and their results suggested a positive
association between prenatal exposure to smoking and RWG, with
a dose-response relationship. The OR of RWG at 9 months of age
for the children of mothers who smoked heavily ( 11cigarettes
daily), after adjusting for birth weight and gestation, was 1.85 (95%
CI not reported). In our study, the relative risk of RWG, after
adjusting for birth weight, in infants whose mothers smoked 11
cigarettes per day was 1.80, which was close to Lyte’s figure.
The mechanisms of the link between maternal smoking during
pregnancy and RWG have not been fully clarified, but several hypotheses
can be put forward. First, nicotine, which is transported
across the placenta, may explain the physiologic effects of smoking
during pregnancy.22 In an animal study, rats prenatally exposed to
low doses of nicotine were not smaller at birth but had higher fat
levels.23 It has also been suggested that maternal smoking during
pregnancy may be associated with lower cord blood leptin,22 and
that a low concentration of this hormone at birth may provide a
signal for catch-up growth by inhibiting satiety.7 Thus, it is
conceivable that the mechanisms linking prenatal smoking with
RWG bypass birth weight and type of feeding.
The main strength of our study is that we had access to a large
population-based dataset rather than a hospital-based dataset.
Second, we collected information about maternal smoking status
before and during pregnancy, and we had information on number
of cigarettes smoked per day during pregnancy. Thus, we could
observe increased risk of RWG in infants born to ex-smokers and
light smokers (1e5 cigarettes per day), which allowed us to assess
the dose-response relationship. Also, because we were able to
examine the infants in early infancy (at 3e5 months of age), the
influence of lifestyle factors was minimized.
The main limitation of our study is that maternal smoking status
was assessed using self-report. Because of the self-report format of
our study, the subjects in the ex-smoker group may actually have
included some current smokers. Tong et al. reported that 10% of
woman who claimed to have stopped smoking showed biochemical
evidence of continued smoking.24 It is possible that we overestimated
the risk of RWG in the ex-smoker group, and that
smoking cessation during pregnancy may have a greater effect on
RWG in early infancy than the study results indicate. Next, a recent
study on the relationship between the socioeconomic status of
mothers and RWG in their infants is worthy of attention.25 We did
not have access to information on socio-economic status, such as
maternal education, household income, and occupation. Further
studies that include information on socio-economic status will be
necessary. Last, our subjects were from Okinawa Prefecture, which
has a distinct culture from the rest of Japan, including food and
lifestyle. Therefore, our subjects might not be representative of
pregnant Japanese woman.
In conclusion, our results from a large population-based dataset
clearly show that maternal smoking during pregnancy results in
dose-dependent increases in the risk of RWG in their offspring in
early infancy. This finding is significant because previous studies of
maternal smoking status and RWG in infants have not included
Asian subjects, who differ physically from Western subjects.
Conflicts of interest
None declared.
Acknowledgements
This work was supported by the Ministry of Health, Labour and
Welfare of Japan, Jisedai-Ippan (H25-002, http://www.mhlw.go.jp/
seisakunitsuite/bunya/hokabunya/kenkyujigyou/hojokin-kouboh25/gaiyo/08.html)
to ZY.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.je.2016.10.005.
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