smoking and alcohol drinking during …ecnis.openrepository.com/ecnis/bitstream/10146... · the...
TRANSCRIPT
419
R E V I E W P A P E R
International Journal of Occupational Medicine and Environmental Health 2015;28(3):419 – 443http://dx.doi.org/10.13075/ijomeh.1896.00424
SMOKING AND ALCOHOL DRINKING DURING PREGNANCY AS THE RISK FACTORS FOR POOR CHILD NEURODEVELOPMENT – A REVIEW OF EPIDEMIOLOGICAL STUDIESKINGA POLAŃSKA, JOANNA JUREWICZ, and WOJCIECH HANKE
Nofer Institute of Occupational Medicine, Łódź, PolandDepartment of Environmental Epidemiology
AbstractMaternal active and passive smoking and low or moderate alcohol drinking during pregnancy, taking into account the level of exposure and developmental or behavioral outcomes, are recognized as a significant issue from both a clinical and a pub-lic health perspective. The article aims at evaluating the impact of prenatal exposure to tobacco smoke constituents and low or moderate alcohol drinking during pregnancy on children neurodevelopment by reviewing the most recently published literature. Relevant studies were identified by searching the Pubmed, Medline and Ebsco literature databases. This review is restricted to 29 human studies published in English in peer reviewed journals since 2006. The studies published recently continued to show some relationship between tobacco smoke exposure, from active and passive maternal smoking during pregnancy, and children’s psychomotor development independent of other variables, but this relationship is not straightfor-ward. The association is mostly consistent for measures of academic achievements and behavioral problems which require further attention. The results of the studies on low or moderate exposure to alcohol are not fully conclusive, but some of them suggest that consumption of alcohol during pregnancy may adversely affect children’s intelligence quotient (IQ), mental health, memory and verbal or visual performance. As the reviewed studies indicate, maternal lifestyle during preg-nancy like alcohol drinking or smoking may affect children neurodevelopment. All effort should be taken to eliminate such exposure to ensure appropriate children’s development.
Key words:Children, Behavior, Prenatal smoking, Prenatal alcohol, Neurodevelopment
This work is funded from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 603946 (Health and Environment-wide Associations based on Large population Surveys – HEALS).Received: August 13, 2014. Accepted: September 28, 2014.Corresponding author: K. Polańska, Nofer Institute of Occupational Medicine, Department of Environmental Epidemiology, św. Teresy 8, 91-348 Łódź, Poland (e-mail: [email protected]).
INTRODUCTIONNowadays special attention is focused on maternal ac-tive and passive smoking and low or moderate alcohol drinking during pregnancy and their impact on chil-dren’s neurodevelopment. Child cognitive development and behavior is determined by genetic, environmental,
and social factors interacting in complex ways. None of them is sufficient to explain population neurodevelop-mental abnormalities. Except for single-gene disorders, heredity accounts for about 50% of the variance of cog-nitive, behavioral, and personality traits among individ-uals [1]. This, of course, implies that the other 50% of
Nofer Institute of Occupational Medicine, Łódź, Poland
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)420
– referred to outcome: neurodevelopment, neurobehav-ior, psychomotor development, behavioral problems, cognitive development, IQ, mental health, school achievements and learning abilities.
Relevant studies were also identified via review of ref-erences cited in all published studies. To be eligible for the review, each study must have used a measure of ex-posure to maternal active/passive smoking or low/mod-erate alcohol drinking during pregnancy period and at least 1 measure of neurocognitive function in the off-spring. For this review, postnatal exposure to tobacco con-stituents and heavy or binge drinking by pregnant women was not considered for inclusion.Additionally, studies were excluded if the exposure to dif-ferent types of toxicants were combined into a single vari-able, making it impossible to determinate the association between exposures of interests and child neurodevelop-ment. From each study, the following information was ab-stracted: year of publication, country in which the study was performed, study design and population, assessment of exposure (including biomarkers), child neurodevelop-ment (including a neurodevelopmental test used) and confounding factors.Finally, this review includes human studies published in English in peer reviewed journals since 2006. Fully adjust-ed analyses are presented where available. Taking into ac-count the great heterogeneity between the studies, mostly in outcome assessment and statistical analyses, a meta-analysis, although considered, was not possible.In summary 29, out of total 83 articles identified, meet eligibility criteria and were included in the present review (Figure 1).
Description of the state of knowledgeExposure to active and passive smoking during pregnancy and children neurodevelopmentBased on the data from epidemiological studies, we can as-sume that about 20–30% of women actively smoke during
variability must be due to environmental and/or lifestyle influences.In general, the fetal development is regarded as the most vulnerable period of exposure to 2 modifi-able lifestyle factors, such as tobacco and alcohol. Even a small increase in developmental risk associated with prenatal exposure to the above factors may be sufficient to move significant numbers of children into the de-velopmentally delayed range of functioning, requiring early intervention services. As children grow, deficits in socio-emotional function and intellectual abilities become increasingly salient, particularly with regard to social judgment, interpersonal skills, antisocial behav-ior and academic achievements.Previously published literature review [2] indicated that maternal smoking, drinking and cannabis use during pregnancy may be associated with neurobehavioral and cognitive outcomes, although not all research supports this statement. The review mostly pointed the limitations in study design and analysis such as retrospective study design, exposure assessment based on questionnaire data and lack of adequate control over confounding factors.The aim of the present paper is to provide the review of the literature to assess the potentially harmful impact of fetal exposure to the risk factors such as tobacco and low and moderate alcohol intake on children cognitive devel-opment and behavioral problems and to identify direc-tions for future research.
Criteria for inclusion of studies into the reviewEpidemiological studies focused on the prenatal exposure to tobacco and alcohol and children neurodevelopment were identified by a search of the Pubmed, Medline and Ebsco literature databases. The combination of the fol-lowing key words was used: – referred to the exposure: pregnancy, prenatal exposure,
maternal smoking, environmental tobacco smoke expo-sure [ETS], alcohol;
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 421
adjustment for birth weight [6]. No statistically significant association was found after adjustment for additional co-variates (p > 0.05). The analysis by Julvez et al. (2007) suggests that maternal smoking during pregnancy lowered cognitive development in children at 4 years of age (repre-sented by global cognitive score, verbal score, quantitative score, executive function score and working memory) [7]. Recently published analysis, based on the data from pro-spective Polish Mother and Child Cohort, with assessment of exposure based on biomarker measurements (3 times in pregnancy and in children at 1 and 2 years of age), indicat-ed that cotinine level in saliva collected during pregnancy was significantly associated with decreased motor abili-ties at 24 months of age (p = 0.02) and not with cognitive and language achievements after controlling for variety of confounders including ETS exposure after birth [8].The larger amount of studies evaluating the impact of prenatal exposure to active maternal smoking on cogni-tive development, intelligence, and intellectual impair-ment focused on older children including preschool children and adolescents [9–15]. Although some of them indicated the association between such exposure and de-creased IQ score or cognitive delay, there is the contro-versy whether possible confounders have been adequately
pregnancy and about half of the non-smoking pregnant women are exposed to passive smoking [3]. It is also im-portant to notice that almost half of the child population is involuntarily exposed to tobacco smoke at home [4].The effect of maternal active smoking during pregnancy on neurodevelopment in young children (aged 4 or younger) has been inconsistent (Table 1). This can be due to not suf-ficiently sensitive assessment tools for small children, diffi-culties in testing very young babies, or the fact that effects of pollutants may become apparent only with maturation of the brain over time. The results from population-based birth cohort (Generation R Study) indicated that children of mothers who continued smoking during pregnancy had higher risk of behavioral problems at 18 months com-pared to the children of mothers who never smoke with adjustment for age and gender (p < 0.05) [5]. That asso-ciation was strongly confounded by parental characteris-tics. After additional adjustment for parental education, family income and parental psychiatric symptoms the re-sults were not statistically significant (p > 0.1). The data from Quebec Longitudinal Study of Children’s Develop-ment showed an association between maternal smoking in pregnancy and reduced intelligence and memory scores (p ≤ 0.003) in unadjusted analysis with no changes after
7 papers added after reviewof references cited in identified papers
76 papers reviewed for further assessment
Pubmed, Medline, Ebsco databases(N = 317)
29 articles included in the review
241 papers excluded after screening titleand abstract for relevance to the research question
54 papers excluded after screening for relevant and sufficient information:– 15 review papers– 15 papers focused on fetal alcohol syndrome– 2 papers evaluated binge and heavy drinking– 11 papers focused on postnatal environmental tobacco smoke exposure– 6 papers in which the exposure to different types of toxicants were combined into single variable making it
impossible to determinate the association between exposures of interests and child neurodevelopment– 5 papers focused on the mechanism of exposure to environmental factors and children neurodevelopment
Fig. 1. Flowchart showing the process of identification of relevant studies for the review
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)422
Tabl
e 1. E
xpos
ure t
o ac
tive a
nd p
assiv
e sm
okin
g dur
ing p
regn
ancy
and
child
ren
neur
odev
elopm
ent
Stud
y pop
ulat
ion
Type
of s
tudy
Expo
sure
in
form
atio
n
Test
used
fo
r cog
nitiv
e m
easu
rem
ent
Conf
ound
ing f
acto
rsRe
sults
Refe
renc
e
Uni
ted
Stat
es: 5
578
child
ren
betw
een
5–14
year
s of a
ge
US
Natio
nal
Long
itudi
nal
Surv
ey o
f You
th
inte
rview
wi
th m
othe
rs du
ring
preg
nanc
y
Peab
ody
Indi
vidua
l Ac
hiev
emen
t Te
st
ethn
icity,
mat
erna
l age
, mat
erna
l IQ
, m
ater
nal e
duca
tion,
inco
me,
birth
we
ight,
birth
ord
er, c
hild
gend
er,
cogn
itive
stim
ulat
ion,
emot
iona
l su
ppor
t, alc
ohol
cons
umpt
ion
durin
g pre
gnan
cy, il
licit
drug
use
, br
eastf
eedi
ng, m
othe
r res
idin
g with
sp
ouse
or p
artn
er
in u
nadj
uste
d an
alysis
the o
ffspr
ing
of m
othe
rs wh
o sm
oked
≥ 1
pack
of
ciga
rette
s/day
dur
ing p
regn
ancy
ha
d IQ
scor
e 2.9
poin
ts lo
wer t
han
child
ren
of n
on-sm
okin
g mot
hers
(p <
0.00
1), t
he li
ght e
xpos
ure w
as
asso
ciate
d wi
th 1.
7 poi
nt d
ecre
men
t (p
< 0.
001)
; afte
r adj
ustm
ent t
he
resu
lts w
ere n
ot st
atist
ically
sign
ifica
nt
(p =
0.9)
Batty
et al
. (2
006)
[9]
Swed
en: o
ffspr
ing a
t ag
e 15 y
ears
amon
g m
ore t
han
400 0
00
male
and
fem
ale
stude
nts b
orn
1983
th
roug
h 19
87
popu
latio
n-ba
sed
Swed
ish
Coho
rt stu
dy
info
rmat
ion
abou
t m
ater
nal
smok
ing f
rom
M
edica
l Birt
h Re
giste
r
scho
ol
perfo
rman
ce
from
Nat
iona
l Sc
hool
Reg
ister
mat
erna
l age
, par
ity, m
ater
nal
educ
atio
n, m
ater
nal s
ocio
econ
omic
cate
gory
, hom
e own
ersh
ip, c
hild
ge
nder
, Apg
ar sc
ore a
t 5 m
in, b
irth
weigh
t, len
gth,
hea
d cir
cum
fere
nce,
gesta
tiona
l age
mat
erna
l sm
okin
g com
pare
d wi
th
no to
bacc
o us
e dur
ing p
regn
ancy
wa
s asso
ciate
d wi
th an
incr
ease
d ris
k of p
oor s
choo
l per
form
ance
: fo
r 1–9
ciga
rette
s/day
OR
= 1.
6 (9
5% C
I: 1.5
9–1.6
3) an
d fo
r 10 o
r m
ore c
igare
ttes/d
ay O
R =
1.9 (
95%
CI
: 1.86
–1.98
); th
e risk
rem
ained
un
chan
ged
with
adju
stmen
t for
birt
h ou
tcom
es; i
f the
mot
hers
had
smok
ed
in 1s
t but
not
2nd
preg
nanc
y, th
e yo
unge
r sib
lings
was
also
at in
crea
sed
risk o
f poo
r sch
ool p
erfo
rman
ce
Lam
be et
al.
(200
6) [1
7]
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 423
Finl
and:
6 38
8 ch
ildre
n
at 6
mon
ths,
5 a
nd 12
year
s of
age
Hels
inki
Lo
ngitu
dina
l pr
ojec
t
inte
rview
wi
th m
othe
rs du
ring
preg
nanc
y at
each
pre
nata
l vis
it an
d at
fo
llow-
up
Infa
nt
Tem
pera
men
t Q
uesti
onna
ire,
Pres
choo
l Te
mpe
ram
ent
Que
stion
naire
, Sc
hool
-Age
Te
mpe
ram
ent
Que
stion
naire
, Sc
hool
-Age
Be
havio
r Pr
oblem
s Q
uesti
onna
ire,
Stud
ent G
rade
Re
ports
socio
econ
omic
statu
s, m
ater
nal
age,
the s
ympt
oms o
f upp
er
resp
irato
ry in
fecti
on an
d na
usea
, m
ater
nal p
sych
iatric
hos
pita
lizat
ion,
ps
ycho
logic
al di
stres
s dur
ing
preg
nanc
y, ho
spita
lizat
ion
from
ac
ciden
ts
mat
erna
l sm
okin
g dur
ing p
regn
ancy
wa
s sign
ifica
ntly
asso
ciate
d with
infa
nt
tem
pera
men
t (di
stres
s to n
ovelt
y: f =
3.0,
p < 0.
05; b
iolo
gical
irreg
ular
ity:
f = 3.
7, p <
0.05
), pr
esch
ool
tem
pera
men
t (ac
tivity
leve
l: f =
5.7,
p < 0.
01; n
egat
ive em
otio
nalit
y: f =
3.1,
p < 0.
05) a
nd 12
year
s of
age t
empe
ram
ent (
task
orien
tatio
n:
f = 3.
7, p <
0.05
; em
otio
nal r
eacti
vity:
f = 3.
8, p <
0.05
), be
havio
r pro
blem
s (d
istra
ctibil
ity: f
= 4.
1, p <
0.05
; im
mat
urity
: f =
4.0,
p < 0.
05;
nega
tive e
mot
iona
lity:
f =
3.3,
p < 0.
05) a
nd ac
adem
ic
perfo
rman
ce (o
vera
ll aca
dem
ic av
erag
e: f =
4.6,
p < 0.
01)
Mar
tin et
al.
(200
6) [1
6]
Cana
da: 1
544
child
ren
at
3.5 y
ears
of
age
Qué
bec
Long
itudi
nal
Stud
y of
Child
ren’
s D
evelo
pmen
t
inte
rview
with
m
othe
rs af
ter
birth
Peab
ody
Pictu
re
Voca
bular
y Te
st, W
echs
ler
Pres
choo
l an
d Pr
imar
y Sc
ale o
fIn
telli
genc
e, Vi
suall
y Cue
d Re
call
task
birth
weig
ht, m
ater
nal e
duca
tion,
fa
mily
inco
me,
mat
erna
l re
spon
siven
ess,
invo
lvem
ent,
fam
ily
dysfu
nctio
n
expo
sure
asso
ciate
d wi
th re
duce
d in
telli
genc
e (W
echs
ler sc
ale:
β =
–0.08
, p =
0.00
3; Pe
abod
y tes
t: β
= –0
.1, p
< 0.
001)
and
mem
ory
(Visu
ally C
ued
Reca
ll: β
= –0
.1,
p <
0.00
1) sc
ores
in u
nadj
uste
d an
alyse
s, wi
th n
o ch
ange
afte
r ad
justm
ent f
or b
irth
weigh
t; th
ere i
s no
stat
istica
lly si
gnifi
cant
asso
ciatio
n af
ter a
djus
tmen
t for
addi
tiona
l co
varia
tes (
p ≤
0.3)
Hui
jbre
gts e
t al.
(200
6) [6
]
Austr
alia:
3 794
ch
ildre
n
at 14
year
s of
age
Mat
er-
Uni
versi
ty St
udy o
f Pr
egna
ncy,
popu
latio
n-ba
sed
birth
co
hort
study
inte
rview
wi
th m
othe
rs du
ring
preg
nanc
y
Rave
n’s
Stan
dard
Pr
ogre
ssive
M
atric
es
child
gend
er, m
ater
nal a
ge at
birt
h,
ethn
icity,
grav
idity
, fam
ily in
com
e, m
ater
nal e
duca
tion,
pat
erna
l ed
ucat
ion,
foet
al di
stres
s, du
ratio
n of
lab
our a
nd m
ode o
f deli
very
, Apg
ar
scor
es, b
irth
weigh
t-for
-ges
tatio
nal-
age,
brea
stfee
ding
, heig
ht an
d BM
I z-s
core
s at a
ge 5
expo
sure
asso
ciate
d wi
th
a 1.4-
poin
t red
uctio
n (p
= 0.
01)
in in
telli
genc
e sco
res c
ontro
lling
for
child
sex a
nd p
aren
tal c
hara
cteris
tics,
1.2 p
oint
redu
ction
(p =
0.03
) wi
th ad
ditio
nal c
ontro
lling
for
char
acte
ristic
s of l
abou
r, Ap
gar s
core
s an
d bi
rth w
eight
; no
asso
ciatio
n af
ter a
dditi
onal
adju
stmen
t for
br
eastf
eedi
ng, h
eight
and
weigh
t (p
= 0.
4)
Lawl
or et
al.
(200
6) [1
0]
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)424
Spain
: 420
child
ren
at 4
year
s of a
geAs
thm
a M
ultic
ente
r In
fant
Coh
ort
Stud
y
inte
rview
du
ring 3
rd
trim
este
r of
preg
nanc
y an
d ev
ery
ear u
p to
ag
e 4 ye
ars
of th
e chi
ld
McC
arth
y Sc
ales o
f Ch
ildre
n’s
Abili
ties
hom
e loc
atio
n, m
ater
nal a
lcoho
l co
nsum
ptio
n, m
othe
r’s so
cial c
lass,
level
of ed
ucat
ion
durin
g pre
gnan
cy,
parit
y, m
arita
l sta
tus,
fath
er’s
educ
atio
n, ch
ild ge
nder
, birt
h we
ight
and
heigh
t, br
eastf
eedi
ng d
urat
ion,
pa
ssive
smok
ing,
scho
ol se
ason
, ag
e dur
ing t
est a
dmin
istra
tion
and
evalu
ator
mat
erna
l sm
okin
g dur
ing p
regn
ancy
wa
s asso
ciate
d wi
th a
decr
ease
of
child
ren’
s glo
bal c
ogni
tive (
β =
−0.6
; 95
% C
I: −
1.1−
(−0.0
9)),
verb
al (β
= −
0.6; 9
5% C
I: −
1.1−
0.07)
, qu
antit
ative
(β =
−0.6
; 95%
CI:
−1.1
−0.0
6), e
xecu
tive f
uncti
on
(β =
−0.7
; 95%
CI:
−1.2
−0.2
) and
wo
rkin
g mem
ory s
core
s (β
= –0
.5;
95%
CI:
−0.9
−0.0
1)
Julve
z et a
l. (2
007)
[7]
Taiw
an: 1
45 ch
ildre
n at
2 ye
ars o
f age
Ta
iwan
Birt
h Pa
nel S
tudy
inte
rview
wi
thin
3 da
ys
afte
r deli
very
an
d 2 y
ears
postp
artu
m,
cotin
ine l
evel
in co
rd b
lood
The
Com
preh
ensiv
e D
evelo
pmen
tal
Inve
ntor
y for
In
fant
s and
To
ddler
s
mat
erna
l edu
catio
n, n
atio
nalit
y, in
com
e, ch
ild ge
nder
, ges
tatio
nal a
ge,
hom
e obs
erva
tion
for m
easu
rem
ent o
f th
e env
ironm
ent s
core
, pos
tnat
al ET
S ex
posu
re
mat
erna
l ETS
expo
sure
dur
ing
preg
nanc
y was
sign
ifica
ntly
nega
tively
as
socia
ted
with
dev
elopm
enta
l qu
otien
ts of
the w
hole
test
(β =
–7.9,
p
= 0.
002)
, cog
nitiv
e (β
= –5
.4,
p =
0.04
), lan
guag
e (β
= –7
.9,
p =
0.00
2), fi
ne-m
otor
(β =
–7.5,
p
= 0.
004)
, soc
ial (β
= –7
.2, p
= 0.
03)
subt
ests;
CYP
1A1 I
le462
Val a
nd
GST
T1 m
etab
olic
gene
s can
mod
ify
the e
ffect
of co
rd b
lood
cotin
ine o
n ea
rly ch
ild n
euro
deve
lopm
ent
Hsie
h et
al.
(200
8) [2
1]
Uni
ted
Stat
es: 4
827
child
ren
at
4 an
d 7 y
ears
of
age
Colla
bora
tive
Perin
atal
Proj
ect,
birth
co
hort
study
inte
rview
wi
th m
othe
rs du
ring
preg
nanc
y
Stan
ford
-Bine
t In
tellig
ence
Sc
ale, W
echs
ler
Intel
ligen
ce
Scale
for
Child
ren,
acad
emic
perfo
rman
ce
with
Wide
Ran
ge
Achie
veme
nt
Test
pare
ntal
educ
atio
n, o
ccup
atio
n,
inco
me,
mat
erna
l mar
ital s
tatu
s, m
ater
nal e
mpl
oym
ent s
tatu
s, pr
esen
ce
of th
e hus
band
or f
athe
r of t
he b
aby i
n th
e hou
seho
ld, h
ouse
hold
crow
ding
, fa
mily
hist
ory o
f men
tal i
llnes
s, nu
mbe
r of n
euro
logic
and
psyc
hiat
ric
cond
ition
s pre
sent
dur
ing p
regn
ancy
, m
ater
nal a
ge, n
umbe
r of p
rior
preg
nanc
ies, p
ater
nal a
ge
heav
y exp
osur
e (≥
20 ci
gare
ttes)
asso
ciate
d wi
th re
duce
d in
telli
genc
e at
age 4
year
s (β
= −
0.6, p
= 0.
01)
and
age 7
year
s (β
= −
1.3, p
< 0.
001)
an
d ac
adem
ic ac
hiev
emen
t at a
ge
7 yea
rs (re
adin
g: β
= −
1.4, p
< 0.
001;
spell
ing:
β =
−1.0
, p <
0.00
1), b
ut n
ot
signi
fican
t in
fixed
effe
cts m
odel
for
siblin
g rela
tions
hip
(p >
0.05
)
Gilm
an et
al.
(200
8) [1
1]
Tabl
e 1. E
xpos
ure t
o ac
tive a
nd p
assiv
e sm
okin
g dur
ing p
regn
ancy
and
child
ren
neur
odev
elopm
ent –
cont
.
Stud
y pop
ulat
ion
Type
of s
tudy
Expo
sure
in
form
atio
n
Test
used
fo
r cog
nitiv
e m
easu
rem
ent
Conf
ound
ing f
acto
rsRe
sults
Refe
renc
e
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 425
The N
ethe
rland
s: 4 6
80 ch
ildre
n at
18 m
onth
s of
age
The G
ener
atio
n R
Stud
y, po
pulat
ion-
base
d bi
rth
coho
rt stu
dy
inte
rview
with
m
othe
rs at
ea
ch tr
imes
ter
of p
regn
ancy
Child
Beh
avio
r Ch
eckl
ist fo
r To
ddler
s
age,
child
gend
er, n
atio
nal o
rigin
, pa
rent
al ed
ucat
ion,
fam
ily in
com
e, pa
rent
al ps
ychi
atric
sym
ptom
s
child
ren
of m
othe
rs wh
o co
ntin
ued
smok
ing d
urin
g pre
gnan
cy h
ad h
igher
ris
k of b
ehav
iora
l pro
blem
s com
pare
d to
the c
hild
ren
of m
othe
rs
who
neve
r sm
oke (
OR
= 1.
6, 95
% C
I: 1.2
−2.1
) with
adju
stmen
t for
age
and
gend
er; s
mok
ing b
y fat
her w
hen
mot
her d
id n
ot sm
oke w
as re
lated
to
high
er ri
sk o
f beh
avio
ral p
robl
ems;
afte
r adj
ustm
ent f
or ad
ditio
nal
conf
ound
ers t
he re
sults
wer
e not
sta
tistic
ally s
ignifi
cant
(p >
0.1)
Roza
et al
. (2
009)
[5]
Uni
ted
Stat
es,
Arka
nsas
, Geo
rgia,
No
rth C
arol
ina
and
Uta
h: 10
5 572
ch
ildre
n at
8 ye
ars
of ag
e
Activ
e Su
rveil
lance
Pr
ojec
t
mot
her’s
sm
okin
g de
term
ined
fro
m b
irth
certi
ficat
e
inte
llectu
al di
sabi
lity
(IQ ≤
70)
mat
erna
l edu
catio
n, m
ater
nal r
ace,
mat
erna
l age
, mar
ital s
tatu
s, ch
ild
gend
er, b
irth
year
and
study
site
the r
isk o
f int
ellec
tual
disa
bilit
y was
m
ildly
eleva
ted
amon
g chi
ldre
n wh
ose
mot
hers
smok
ed ≥
20 ci
gare
ttes/d
ay
durin
g pre
gnan
cy (R
R =
1.3,
95%
CI:
1.0−
1.9) a
fter a
djus
tmen
t; th
e effe
ct of
expo
sure
sign
ifica
ntly
diffe
red
for
male
s (RR
= 1.
8, 95
% C
I: 1.2
−2.6
) co
mpa
red
with
fem
ales (
RR =
0.81
, 95
% C
I: 0.4
−1.5
); su
pplem
enta
l an
alyse
s rev
eal s
ubsta
ntial
co
nfou
ndin
g of t
his r
elatio
nshi
p by
so
cio-e
cono
mic
indi
cato
rs
Brau
n et
al.
(200
9) [1
2]
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)426
Cana
da: 5
03 ch
ildre
n at
12–1
8 yea
rs
of ag
e
Sagu
enay
Yo
uth
Stud
yin
terv
iew w
ith
mot
hers
Wec
hsler
In
telli
genc
e Sc
ale fo
r Ch
ildre
n;
Woo
dcoc
k-Jo
hnso
n III
, Sp
ellin
g; Ch
ildre
n‘s
Mem
ory S
cale;
Se
lf O
rder
ed
Poin
ting T
ask;
Ru
ff2-&
-7
Selec
tive
Atte
ntio
n Te
st;
Stro
op C
olou
r-W
ord
Test;
Ve
rbal
Flue
ncy
Test
hous
ehol
d in
com
e, pa
rent
al ed
ucat
ion,
m
ater
nal a
lcoho
l use
dur
ing p
regn
ancy
, ET
S ex
posu
re d
urin
g pre
gnan
cy,
num
ber o
f pre
gnan
cies,
mat
erna
l age
at
deli
very
, birt
h we
ight,
brea
stfee
ding
, bi
rth o
rder
, par
enta
l war
mth
, par
ent
mon
itorin
g, pa
rent
al an
tisoc
ial
beha
vior
no ef
fect
of m
ater
nal s
mok
ing d
urin
g pr
egna
ncy o
n co
gniti
ve ab
ilitie
s of
adol
esce
nt o
ffspr
ing a
fter m
atch
ing
by m
ater
nal e
duca
tion
Kafo
uri e
t al.
(200
9) [1
3]
Austr
alia:
4 294
ch
ildre
n
at 14
year
s of a
ge
Mat
er-
Uni
versi
ty St
udy o
f Pr
egna
ncy,
popu
latio
n-ba
sed
birth
co
hort
study
inte
rview
wi
th m
othe
rs du
ring
preg
nanc
y an
d at
each
fo
llow-
up
(6 m
onth
s, 5 a
nd 14
year
s af
ter d
elive
ry)
repo
rts o
f ac
adem
ic pe
rform
ance
ov
erall
and
in E
nglis
h,
scien
ce an
d m
athe
mat
ics
exac
t age
at ex
amin
atio
n, ch
ild ge
nder
, m
ater
nal a
ge, e
duca
tion,
inco
me,
mar
ital s
tatu
s, m
ater
nal a
lcoho
l co
nsum
ptio
n, m
ater
nal d
epre
ssion
, fa
mily
com
mun
icatio
n, b
irth
weigh
t, br
eastf
eedi
ng, b
ehav
iora
l pro
blem
s at
14 ye
ars
mat
erna
l sm
okin
g dur
ing p
regn
ancy
wa
s asso
ciate
d wi
th sm
all d
ecre
men
ts in
offs
prin
g aca
dem
ic pe
rform
ance
(O
R =
1.4,
95%
CI:
1.1−
1.7) a
fter
adju
stmen
t for
varie
ty of
facto
rs
O’C
allag
han
et al
. (20
10)
[14]
Polan
d: 46
8 chi
ldre
n at
3 ye
ars o
f age
Birth
Coh
ort
Stud
yqu
estio
nnair
e du
ring
preg
nanc
y an
d af
ter
deliv
ery
Bayle
y Men
tal
Dev
elopm
ent
Inde
x of B
ayley
Sc
ales o
f Inf
ant
Dev
elopm
ent
(BSI
D-II
)
mat
erna
l edu
catio
n, ch
ild, p
rena
tal
expo
sure
to le
adth
e men
tal d
evelo
pmen
t ind
ex sc
ore
corre
lated
inve
rsely
with
the n
umbe
r of
ciga
rette
s sm
oked
dail
y by o
ther
ho
useh
old
mem
bers
at h
ome o
ver
preg
nanc
y per
iod
(r =
−0.2
, p
< 0.
001)
Jedr
ycho
wski
et
al. (
2010
) [2
2]
Tabl
e 1. E
xpos
ure t
o ac
tive a
nd p
assiv
e sm
okin
g dur
ing p
regn
ancy
and
child
ren
neur
odev
elopm
ent –
cont
.
Stud
y pop
ulat
ion
Type
of s
tudy
Expo
sure
in
form
atio
n
Test
used
fo
r cog
nitiv
e m
easu
rem
ent
Conf
ound
ing f
acto
rsRe
sults
Refe
renc
e
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 427
Swed
en: 6
54 70
7 ch
ildre
n at
15 ye
ars
of ag
e
data
colle
cted
from
po
pulat
ion-
base
d re
giste
rs
Med
ical B
irth
Regis
ter,
com
plet
ed
befo
re 15
th
week
of
gesta
tion
scho
ol
perfo
rman
ce
base
d on
a s
umm
ary
grad
e poi
nt
scor
e of 1
6 di
ffere
nt
subj
ects
from
th
e Nat
iona
l Sc
hool
Re
giste
r, G
rade
9 –
mat
hem
atics
sc
ore
mat
erna
l age
, pat
erna
l age
, birt
h or
der,
gesta
tiona
l age
, not
coha
bitin
g, m
ater
nal a
nd p
ater
nal e
duca
tion
and
occu
patio
n
expo
sure
asso
ciate
d wi
th 0.
5 SD
de
cline
in su
mm
ary g
rade
poi
nt in
un
relat
ed o
ffspr
ing (
β =
−0.6
, p
≤ 0.
05),
redu
ced
to 0.
03 S
D
incr
ease
in fu
ll sib
lings
(β =
0.00
, p
> 0.
05);
expo
sure
asso
ciate
d
with
0.4 S
D d
eclin
e in
mat
hem
atics
sc
ore i
n un
relat
ed o
ffspr
ing
(β =
−0.5
, p ≤
0.05
), re
duce
d
to 0.
02 S
D in
crea
se in
full
siblin
gs
(β =
0.00
, p >
0.05
)
D’O
nofri
o et
al. (
2010
) [1
8]
Repu
blic
of K
orea
: 41
4 inf
ants
at
6 m
onth
s of
age
mul
ticen
ter
pros
pecti
ve
coho
rt stu
dy
ques
tionn
aire
durin
g pr
egna
ncy
and
at 6
mon
ths
postp
artu
m
Bayle
y Sca
les
of In
fant
D
evelo
pmen
t (B
SID
-II)
resid
entia
l are
a, m
ater
nal a
ge, p
re-
preg
nanc
y BM
I, ed
ucat
ion,
inco
me,
child
gend
er, p
arity
, birt
h we
ight,
type
of fe
edin
g
ETS
expo
sure
dur
ing p
regn
ancy
wa
s asso
ciate
d wi
th d
ecre
ase i
n m
enta
l dev
elopm
enta
l ind
ex sc
ore
(−2.8
; 95%
CI:
−5.2
to −
0.4),
and
incr
ease
d th
e risk
of d
evelo
pmen
tal
delay
(OR
= 2.
4, 95
% C
I: 1.2
–4.6)
, ps
ycho
mot
or d
evelo
pmen
tal i
ndex
sc
ore w
as n
ot as
socia
ted
with
ETS
ex
posu
re
Lee e
t al.
(201
1) [2
3]
Uni
ted
Stat
es
Pitts
burg
h:
330 c
hild
ren
at
10 ye
ars
of ag
e
Mat
erna
l H
ealth
Pra
ctice
s an
d Ch
ild
Dev
elopm
ent
Proj
ect,
pros
pecti
ve
study
inte
rview
wi
th m
othe
r du
ring 2
nd
trim
este
r and
af
ter d
elive
ry
cont
inuo
us
perfo
rman
ce
test;
Stro
op
Colo
ur
Wor
d Te
st;
Wid
e Ran
ge
Asse
ssmen
t of
Mem
ory a
nd
Lear
ning
; Tes
t of
Var
iables
of
Atte
ntio
n
mat
erna
l sub
stanc
e use
dur
ing
child
hood
, age
, eth
nicit
y, ch
ild ge
nder
, ch
ild cu
stody
, sin
gle m
othe
rhoo
d, S
ES,
mat
erna
l stre
ssful
life
even
ts, m
ater
nal
socia
l sup
port,
qua
lity a
nd q
uant
ity
of su
ppor
t ava
ilabl
e to
the c
hild
fo
r cog
nitiv
e, so
cial, a
nd em
otio
nal
deve
lopm
ent
expo
sed
offsp
ring h
ad m
ore
delin
quen
t, ag
gres
sive,
and
exte
rnali
zing b
ehav
iors
than
of
fsprin
g who
wer
e not
expo
sed
to
toba
cco
pren
atall
y; th
ey w
ere m
ore
activ
e and
impu
lsive
, had
mor
e pr
oblem
s with
pee
rs, an
d ha
d m
ore
diffi
culty
on
task
s req
uirin
g sele
ctive
at
tent
ion
and
resp
onse
inhi
bitio
n;
the s
ignifi
cant
effe
cts o
f exp
osur
e on
neu
robe
havio
ral o
utco
mes
wer
e fo
und
for ≥
10 ci
gare
ttes/d
ay an
d m
ostly
for 1
st tri
mes
ter e
xpos
ure
Corn
elius
et
al. (
2011
) [1
9]
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)428
Uni
ted
Stat
es,
Chica
go: 2
34
at 5.
9 yea
rs of
age
at 1s
t asse
ssmen
t an
d 2n
d as
sessm
ent
1 yea
r lat
er
Proj
ect o
n H
uman
De-
velo
pmen
t in
Chica
go N
eigh-
bour
hood
s, ne
ighbo
urho
od
cluste
rs
inte
rview
with
m
othe
rsat
tent
ion
netw
ork t
est
socio
econ
omic
statu
s, pr
enat
al alc
ohol
ex
posu
re, b
aseli
ne p
erfo
rman
ce,
gesta
tiona
l age
, birt
h we
ight,
head
cir
cum
fere
nce
expo
sure
thro
ugho
ut p
regn
ancy
as
socia
ted
with
40 m
s slo
wer r
eacti
on
times
com
pare
d to
no
expo
sure
or
expo
sure
thro
ugh
som
e of p
regn
ancy
(p
= 0.
002)
, exp
osur
e not
asso
ciate
d wi
th ac
cura
cy (p
= 0.
7)
Mez
zaca
ppa
et al
. (20
11)
[20]
Den
mar
k: 1
782
child
ren
at 5
year
s of
age
Dan
ish
Natio
nal
Birth
Coh
ort
inte
rview
with
m
othe
rs at
17
gesta
tiona
l we
eks
Wec
hsler
Pr
imar
y and
Pr
esch
ool
Scale
s of
Inte
llige
nce
pare
ntal
educ
atio
n, m
ater
nal I
Q,
mat
erna
l alco
hol c
onsu
mpt
ion
in
preg
nanc
y, th
e gen
der a
nd ag
e of
the c
hild
, tes
ter,
pren
atal
pate
rnal
smok
ing,
mat
erna
l age
and
BMI,
parit
y, fa
mily
/hom
e env
ironm
ent,
postn
atal
pare
ntal
smok
ing,
brea
st fe
edin
g, th
e chi
ld’s
healt
h sta
tus,
and
indi
cato
rs fo
r hea
ring a
nd vi
sion
impa
irmen
ts
unad
juste
d an
alyse
s sho
wed
a sta
tistic
ally s
ignifi
cant
dec
rem
ent
of 4
poin
ts on
full-
scale
IQ as
socia
ted
with
smok
ing ≥
10 ci
gare
ttes/d
ay
com
pare
d to
non
-smok
ing;
afte
r ad
justm
ent f
or p
oten
tial c
onfo
unde
rs,
no si
gnifi
cant
effe
cts o
f pre
nata
l ex
posu
re to
toba
cco
smok
ing w
ere
foun
d
Falgr
een
Erik
sen
et al
. (2
012)
[15]
Polan
d: 40
6 chi
ldre
n at
age o
f 1 ye
ar an
d 19
8 at a
ge 2
year
s
Polis
h M
othe
r an
d Ch
ild
Coho
rt
cotin
ine
level
in sa
liva
colle
cted
once
in ea
ch
trim
este
r of
preg
nanc
y
Bayle
y Sca
les
of In
fant
an
d To
ddler
D
evelo
pmen
t
exam
iner
, chi
ld ge
nder
, age
at
asse
ssmen
t for
com
bine
d an
alysis
(1 o
r 2 y
ears
of ag
e), p
aren
tal a
ge, p
aren
tal
educ
atio
n, m
arita
l sta
tus,
child
nur
sery
at
tend
ance
, cot
inin
e lev
el wi
thin
1st
year
s of l
ife
cotin
ine l
evel
in sa
liva c
ollec
ted
durin
g pre
gnan
cy w
as si
gnifi
cant
ly as
socia
ted
with
dec
reas
ed m
otor
ab
ilitie
s at a
ge o
f 24 m
onth
s (β
= −
2.6, p
= 0.
02);
ther
e wer
e no
stat
istica
lly si
gnifi
cant
effe
cts
of p
rena
tal e
xpos
ure t
obac
co
cons
titue
nts o
n co
gniti
ve an
d lan
guag
e abi
lities
afte
r con
trolli
ng fo
r va
riety
of co
nfou
nder
s
Polan
ska e
t al.
(201
3) [8
]
ETS
– env
ironm
enta
l tob
acco
smok
e; BM
I – b
ody m
ass i
ndex
; IQ
– in
telli
genc
e quo
tient
; SES
– so
cioec
onom
ic sta
tus;
SD –
stand
ard
devia
tion;
HO
ME
– qua
lity o
f hom
e env
ironm
ent.
Tabl
e 1. E
xpos
ure t
o ac
tive a
nd p
assiv
e sm
okin
g dur
ing p
regn
ancy
and
child
ren
neur
odev
elopm
ent –
cont
.
Stud
y pop
ulat
ion
Type
of s
tudy
Expo
sure
in
form
atio
n
Test
used
fo
r cog
nitiv
e m
easu
rem
ent
Conf
ound
ing f
acto
rsRe
sults
Refe
renc
e
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 429
Developmental Inventory for Infants and Toddlers [21]. Similarly, a birth cohort study in Kraków showed an in-verse association between mental development scores at 3 years of age and the number of cigarettes smoked daily by household members at home over the preg-nancy period (p = 0.001) [22]. Another study also sug-gests that the children of non-smoking women exposed to secondhand smoke during pregnancy are at risk of developmental delay [23].In summary, although many studies are focused on the association between active and passive maternal smoking during pregnancy and children’s cognitive, in-tellectual abilities, memory and attention, their results are not fully consistent. However, taking into account that there is some evidence of a risk of such exposure to children’s psychomotor development that may last into adulthood, the problem requires further attention. There is a need to perform better designed studies with adequately assessed exposure level and controlled for potential confounding factors that may contribute to such outcomes, particularly genetic and environmental influences. Additionally, since differences have been re-ported depending on the timing and dose of exposure future studies addressing those issues may provide im-portant information.
Exposure to low and moderate alcohol levels during pregnancy and children neurodevelopmentMaternal alcohol use during pregnancy contributes to a range of effects in exposed children, including hyper-activity and attention problems, learning and memory deficits and problems with social and emotional develop-ment. The most serious consequence of maternal drinking during pregnancy is fetal alcohol syndrome (FAS) [24,25]. Although it seems clear that heavy alcohol consumption during pregnancy can result in FAS, the effects of drinking at low-to-moderate levels on children neurodevelopment are much less clear.
controlled for [9–11,15]. Most of the studies pointed that child cognitive development is strongly influenced by pa-rental IQ, socioeconomic status, home environment and sibling relationship.Some studies indicated that prenatal tobacco smoke exposure can be related to children’s academic perfor-mance. The studies performed in Finland [16], Swe-den [17,18] and Australia [14] have shown a significant association between prenatal exposure and academic performance. Data from Collaborative Prenatal Project indicated significant impact of maternal smoking dur-ing pregnancy on academic achievement at 7 years of age including reading, spelling, arithmetic abilities, but the results were confounded by sibling relationship [11].Studies focused on the impact of prenatal tobacco smoke exposure on memory, attention and executive function provided mixed findings. For example, Kaf-ouri et al. (2009) did not find significant impact of mater-nal smoking in pregnancy on verbal, visual or visuospa-tial memory performance and Stroop Test interference score whereas Cornelius et al. (2011) indicated that per-formance on Stroop Test at 10 years of age was reduced with such exposure but no differences were seen on other task such as the Continuous Performance Test and Test of Variables of Attention [13,19]. Mezzcappa et al. (2011) described that the children exposed to tobacco smoke throughout the pregnancy demonstrated average reac-tion times 40 ms slower on the Attention Networks Tests compared to these who were not exposed or whose moth-ers stopped smoking at the beginning of pregnancy [20].The relationship between maternal environmental to-bacco smoke (ETS) exposure during pregnancy and children neurodevelopment was evaluated in 3 stud-ies [21–23]. A Taiwanese cohort study reported a nega-tive association between cotinine levels and 2-year child neurodevelopment assessed by developmental quotients of the whole test and cognitive, language, fine motor and social subtests of the Comprehensive
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)430
and measures of self-control [33]. Skogerbøet al. (2012) did not observe significant effects of low and moderate alcohol consumption during pregnancy on executive func-tioning at 5 years of age among children from the Danish National Birth Cohort [31]. The next group of the studies is associated with the children IQ measures. In the study performed in United States (Atlanta, Georgia) signifi-cantly lower IQ was found for African-American children at 15 years of age prenatally exposed to alcohol [33]. Ala-ti et al. (2008) assessed the IQ at 8 years of age among children from Avon Longitudinal Study of Parents and Children in England [34]. Prenatal alcohol exposure was associated with lower IQ scores only in univariate analy-ses. In fully adjusted models, there was no strong statisti-cal evidence that maternal alcohol and tobacco consump-tion during pregnancy were associated with childhood IQ. Falgreen Eriksen and co-workers (2012) observed that maternal consumption of low to moderate quantities of al-cohol during pregnancy was not associated with the mean IQ score of preschool children, compared with children of mothers who abstained [35].The Danish researchers performed also a combined analysis of the estimated effects of maternal average weekly alcohol consumption in early and mid-pregnancy on general intelligence, attention and executive function. Multivariate analysis showed no statistically significant effects of average weekly alcohol consumption, either individually or in combination on child’s intelligence, at-tention and executive function [36]. These results rep-licate findings from separate analyses of alcohol con-sumption on child’s intelligence, attention and executive function [31,35].In summary, more compelling and stronger evidence is needed to evaluate the effect of low-to-moderate levels drinking during pregnancy. The evidence needs to be strengthened and the quality of information about drink-ing pattern should be improved. As the acceptable, safe levels of alcohol use during pregnancy have not yet been
Depending on the reviewed studies, the definition of low or moderate alcohol consumption was different. In most of the studies, the low alcohol drinking was de-fined as not more than 1–2 units of alcohol per week or less than 4 drinks per week and moderate drinking as not more than 3–6 units per week or 5 to 8 drinks per week.In the prospective study performed among children from Avon Longitudinal Study of Parents and Children in Eng-land, the consumption of less than 1 drink per week dur-ing the 1st trimester was independently associated with mental health problems in girls at 47 months [26] (Ta-ble 2). In the study performed in United States (Pitts-burgh, Pennsylvania) moderate alcohol exposure during the 1st and 2nd trimesters was related to the poorer com-posite score for African American children at age of 10. Significant relations were also found for the verbal, ab-stract/visual, and quantitative subscales [27].Whereas Underbjerg et al. (2012) based on the Danish Na-tional Birth Cohort found no significant effects on test per-formance in children of mothers drinking up to 8 drinks per week [28]. Also O’Callaghan et al. (2007) did not find association between consumption of less than 1 glass/day in early or late pregnancy and attention, learning or cognitive outcomes among 14 years old children [29]. The strongest estimates of effect were noticed among those consuming 1 or more glasses/day, but the results were not statistically significant. Also, in the prospective cohort study (UK Millennium Cohort Study), children born to mothers who drank up to 1–2 drinks per week during pregnancy were not at increased risk of clini-cally relevant behavioral difficulties or cognitive deficits at 5 years of age [30].One study assesses the low and moderate alcohol con-sumption and executive functioning in children [31]. Executive functions are defined as higher-order psycho-logical abilities involved in goal-oriented behavior under conscious control [32]. Executive functions comprise sev-eral cognitive processes, including planning, organisation,
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 431
Tabl
e 2. E
xpos
ure t
o lo
w an
d m
oder
ate a
lcoho
l lev
els d
urin
g pre
gnan
cy an
d ch
ildre
n ne
urod
evelo
pmen
t
Stud
y pop
ulat
ion
Type
of s
tudy
Expo
sure
info
rmat
ion
Test
used
fo
r cog
nitiv
e m
easu
rem
ent
Conf
ound
ing f
acto
rsRe
sults
Refe
renc
e
Uni
ted
Stat
es,
Pitts
burg
h Pe
nnsy
lvani
a: 63
6 m
othe
r-chi
ld p
airs
exam
ined
at b
irth,
at
8 an
d 18
mon
ths;
and
3, 6,
and
10 ye
ars
Mat
erna
l H
ealth
Pr
actic
es
and
Child
D
evelo
pmen
t Pr
ojec
t –
pros
pecti
ve
study
quan
tity a
nd fr
eque
ncy o
f bee
r, wi
ne, li
quor
, bee
r coo
ler
and
wine
cool
er u
se d
urin
g ea
ch tr
imes
ter o
f pre
gnan
cy;
pren
atal
alcoh
ol u
se w
as
expr
esse
d as
the A
DV o
r the
av
erag
e num
ber o
f drin
ks/d
ay
Stan
ford
-Bin
et
Inte
llige
nce S
cale
mat
erna
l IQ
, age
, in
com
e, m
arita
l sta
tus,
heigh
t, we
ight g
ain
durin
g pre
gnan
cy, r
ace,
parit
y, ge
statio
nal a
ge,
depr
essio
n, so
cial s
uppo
rt
relat
ion
betw
een
alcoh
ol
expo
sure
dur
ing t
he 1s
t (β
= –2
.75, p
< 0.
05) a
nd
2nd
trim
este
rs (β
= –7
.15,
p <
0.01
) and
the c
ompo
site
scor
e for
Afri
can
Amer
ican
child
ren
at ag
e 10;
signi
fican
t rela
tions
wer
e als
o fo
und
for t
he ve
rbal
(2nd
trim
este
r β =
–5.69
, p
< 0.
05),
abstr
act/v
isual
(1st
trim
este
r β =
–3.33
, p
= 0.
05; 2
nd tr
imes
ter
β =
–6.32
, p <
0.05
), an
d qu
antit
ative
reas
onin
g su
bsca
les (2
nd tr
imes
ter
β =
–5.78
, p <
0.05
)
Will
ford
et al
. (2
006)
[27]
Uni
ted
Stat
es, A
tlant
a, G
eorg
ia: 26
5 low
SE
S ad
oles
cent
s (m
ean
age =
15.1
year
s), 12
8 pre
nata
lly
expo
sed
to al
coho
l, 53
cont
rols,
and
84
spec
ial ed
ucat
ion
stude
nts b
orn
to m
othe
rs fir
st re
crui
ted
betw
een
1980
and
1985
fro
m a
pren
atal
clini
c in
serv
ing
a pre
dom
inan
tly
Afric
an-A
mer
ican
popu
latio
n
long
itudi
nal
coho
rtwo
men
wer
e rec
ruite
d
if th
ey re
porte
d dr
inki
ng
at le
ast 2
drin
ks/w
eek d
urin
g pr
egna
ncy
Wec
hsler
In
telli
genc
e Sca
le fo
r Chi
ldre
n,
Wec
hsler
In
divid
ual
Achi
evem
ent
Test,
Vin
eland
Ad
aptiv
e Be
havio
r Sca
les
age,
educ
atio
n, m
onth
ly in
com
e, sm
okin
g, ge
nder
of
the c
hild
adol
esce
nt p
rena
tally
ex
pose
d to
alco
hol h
ad
signi
fican
tly lo
wer I
Q (f
ull
scale
IQ p
< 0.
007;
verb
al IQ
p <
0.01
; per
form
ance
IQ
p <
0.01
)
How
ell et
al.
(200
6) [3
3]
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)432
Austr
alia:
7223
sin
gleto
ns w
hose
m
othe
rs we
re
enro
lled
at th
e 1s
t ant
enat
al vis
it as
sesse
d at
14 ye
ars
The M
ater
-U
nive
rsity
of
Que
ensla
nd
Stud
y of
Preg
nanc
y –
pros
pecti
ve
birth
coho
rt
the a
lcoho
l con
sum
ptio
n ca
tego
ries w
ere a
s fol
lows
(oz/
day)
: 0, 0
.01–0
.249,
0.25–
0.499
, an
d 0.5
or m
ore,
bein
g eq
uiva
lent t
o ni
l, < 1/
2 glas
s, 1/2
to <
1 gla
ss,
and
≥ 1
glass/
day
Wid
e Ran
ge
Achi
evem
ent
Test-
Revis
ed,
Rave
n’s S
tand
ard
Prog
ressi
ve
Mat
rices
Test,
Ch
ild B
ehav
ior
Chec
klist
, You
th
Self
Repo
rt
mat
erna
l BM
I, cig
aret
te
smok
ing,
mat
erna
l ed
ucat
ion,
mat
erna
l age
, sin
gle p
aren
t sta
tus,
low
inco
me i
n pr
egna
ncy
for c
onsu
mpt
ion
of
< 1
glass/
day i
n ea
rly
or la
te p
regn
ancy
was
no
asso
ciate
d wi
th an
y at
tent
ion
(OR
= 1.
0,
95%
CI:
0.8–1
.3), le
arni
ng
(OR
= 1.
0, 95
% C
I: 0.9
–1.2)
or
cogn
itive
out
com
es
(OR
= 0.
8, 95
% C
I: 0.7
–1.01
); ex
posu
re in
late
pr
egna
ncy w
as as
socia
ted
with
incr
ease
d pr
evale
nce
of o
vera
ll lea
rnin
g diffi
culty
(O
R =
0.8,
95%
CI:
0.7–0
.9)
in th
e una
djus
ted,
alth
ough
no
t in
the a
djus
ted
analy
sis
(OR
= 1.
2, 95
% C
I: 0.1
–2.3)
O’C
allag
han
et al
. (20
07)
[29]
Engla
nd: 9
086 c
hild
ren
asse
sses a
t 47,
8 046
ch
ildre
n as
sesse
d at
81, a
nd 5
648
child
ren
asse
ssed
at 93
–108
mon
ths
Avon
Lo
ngitu
dina
l St
udy o
f Pa
rent
s and
Ch
ildre
n –
pros
pecti
ve,
popu
latio
n-ba
sed
study
the m
othe
r was
aske
d ab
out
her f
requ
ency
of d
rinki
ng
alcoh
olic
drin
ks; r
espo
nse
cate
gorie
s wer
e: ne
ver,
< 1
glass/
week
, ≥ 1
glass/
week
, 1 to
2 g
lasse
s/day
, 3 to
9 gla
sses/d
ay,
or >
10 gl
asse
s/day
Stre
ngth
s and
D
ifficu
lties
Q
uesti
onna
ire
mat
erna
l age
, par
ity,
mat
erna
l sm
okin
g and
us
e of c
anna
bis a
nd
othe
r illi
cit d
rugs
in th
e 1s
t trim
este
r, m
ater
nal
educ
atio
n, h
ousin
g, m
arita
l sta
tus
the c
onsu
mpt
ion
of <
1 dr
ink/
week
dur
ing t
he 1s
t tri
mes
ter w
as in
depe
nden
tly
asso
ciate
d wi
th m
enta
l he
alth
prob
lems i
n gir
ls at
47
mon
ths (
OR
= 1.
10,
95%
CI:
0.58–
0.61)
Saya
l et a
l. (2
007)
[26]
Tabl
e 2. E
xpos
ure t
o lo
w an
d m
oder
ate a
lcoho
l lev
els d
urin
g pre
gnan
cy an
d ch
ildre
n ne
urod
evelo
pmen
t – co
nt.
Stud
y pop
ulat
ion
Type
of s
tudy
Expo
sure
info
rmat
ion
Test
used
fo
r cog
nitiv
e m
easu
rem
ent
Conf
ound
ing f
acto
rsRe
sults
Refe
renc
e
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 433
Engla
nd: 4
332 c
hild
ren
asse
ssed
at 8
year
s of
age
Avon
Lo
ngitu
dina
l St
udy o
f Pa
rent
s and
Ch
ildre
n –
coho
rt stu
dy
the i
nfor
mat
ion
abou
t alco
hol
cons
umpt
ion
was b
ased
on
ques
tion:
how
ofte
n th
ey h
ad
drun
k alco
holic
drin
ks d
urin
g th
e first
3 m
onth
s of p
regn
ancy
; Ad
ditio
nally
par
ticip
ants
and
their
par
tner
s wer
e ask
ed h
ow
man
y day
s in
the p
revio
us
mon
th th
ey h
ad d
runk
the
equi
valen
t of 2
pin
ts of
bee
r, 4 g
lasse
s of w
ine o
r 4 p
ub
mea
sure
s of s
pirit
or m
ore
Wes
chler
In
telli
genc
e Sca
le fo
r Chi
ldre
n
socio
-eco
nom
ic sta
tus,
mar
ital s
tatu
s, lev
el of
educ
atio
n, h
ead
of
hous
ehol
d, o
ccup
atio
nal
socia
l clas
s, an
inde
x in
dica
ting t
he cr
owdi
ng
cond
ition
of t
he
hous
ehol
d, et
hnici
ty,
gend
er o
f the
child
, par
ity
pren
atal
alcoh
ol ex
posu
re
was n
ot as
socia
ted
with
lowe
r IQ
scor
es
in m
ultiv
ariat
e ana
lysis
(OR
= 0.
98, 9
5% C
I: 0.8
4–1.1
1)
Alat
i et a
l. (2
008)
[34]
Engla
nd: 1
1 513
ch
ildre
n as
sesse
d
at 5
year
s of a
ge
UK
Mill
enni
um
Coho
rt St
udy
parti
cipan
ts we
re gr
oupe
d ac
cord
ing t
o m
othe
rs’ re
porte
d alc
ohol
cons
umpt
ion
durin
g pr
egna
ncy:
neve
r drin
ker,
not
in p
regn
ancy
, ligh
t (no
t mor
e th
an 1–
2 uni
ts/we
ek o
r per
oc
casio
n), m
oder
ate (
not m
ore
than
3–6 u
nits/
week
or
3–5 u
nits/
occa
sion
Stre
ngth
s and
D
ifficu
lties
Q
uesti
onna
ire
(SD
Q),
Briti
sh
Abili
ty Sc
ales
(BAS
)
no in
form
atio
n-ba
sed
on
abstr
act
at ag
e 5 ye
ars c
ohor
t m
embe
rs bo
rn to
mot
hers
who
dran
k up
to 1–
2 drin
ks/
week
dur
ing p
regn
ancy
we
re n
ot at
incr
ease
d ris
k of c
linica
lly re
levan
t be
havio
ral d
ifficu
lties
(fo
r boy
s OR
= 0.
67,
95%
CI:
0.53–
0.86;
for
girls
OR
= 0.
69, 9
5% C
I: 0.5
0–0.9
6) o
r hyp
erac
tivity
(fo
r boy
s OR
= 0.
73,
95%
CI:
0.58–
0.91;
for
girls
OR
= 0.
71, 9
5% C
I: 0.5
3–0.9
4) co
mpa
red
with
ch
ildre
n of
mot
hers
in th
e no
t-in-
preg
nanc
y gro
up
Kelly
et al
. (2
010)
[30]
Den
mar
k: 1
628 w
omen
an
d th
eir ch
ildre
n at
5 ye
ars o
f age
Dan
ish
Natio
nal B
irth
Coho
rt –
coho
rt stu
dy
info
rmat
ion
on al
coho
l int
ake
durin
g pre
gnan
cy w
as d
erive
d fro
m th
e 1st
pren
atal
inte
rview
; all
mot
hers
were
sam
pled
in
strat
a defi
ned
by th
eir av
erag
e alc
ohol
inta
ke (0
, 1–4
, 5–8
, ≥
9 dr
inks
/wee
k)
The B
ehav
ior
Ratin
g Inv
ento
ry
of E
xecu
tive
Func
tion
(BRI
EF)
pare
ntal
educ
atio
n,
mat
erna
l IQ
, pre
nata
l m
ater
nal s
mok
ing,
age
at te
sting
, and
gend
er o
f ch
ild
not s
ignifi
cant
effe
cts o
f lo
w to
mod
erat
e alco
hol
cons
umpt
ion
durin
g pr
egna
ncy o
n ex
ecut
ive
func
tioni
ng at
the a
ge o
f 5 y
ears
(mea
n di
ffere
nces
1.2
0, 95
% C
I: –0
.54–2
.95)
Skog
erbø
et
al. (2
012)
[31]
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)434
Den
mar
k: 1
628 w
omen
an
d th
eir ch
ildre
n at
5 ye
ars o
f age
Dan
ish
Natio
nal B
irth
Coho
rt – c
ohor
t stu
dy
info
rmat
ion
on al
coho
l int
ake
durin
g pre
gnan
cy w
as d
erive
d fro
m th
e 1st
pren
atal
inte
rview
; all
mot
hers
were
sam
pled
in
strat
a defi
ned
by th
eir av
erag
e alc
ohol
inta
ke (0
, 1–4
, 5–8
, ≥ 9
drin
ks/w
eek)
Test
of E
very
day
Atte
ntio
n fo
r Ch
ildre
n at
Five
(T
EACh
-5)
pare
ntal
educ
atio
n,
mat
erna
l IQ
, mat
erna
l sm
okin
g in
preg
nanc
y, th
e chi
ld’s
age a
t tes
ting,
gend
er, t
este
r, BM
I, pa
rity,
hom
e en
viron
men
t, po
stnat
al sm
okin
g in
the h
ome,
child
’s he
alth
statu
s, an
d in
dica
tors
for h
earin
g an
d vis
ion
impa
irmen
ts
no si
gnifi
cant
effe
cts o
n te
st pe
rform
ance
in ch
ildre
n of
mot
hers
drin
king
up
to
8 drin
ks/w
eek (
OR
= 3.
50,
95%
CI:
1.15–
10.68
)
Und
erbj
erg
et al
. (20
12)
[28]
Den
mar
k: 1
628 w
omen
an
d th
eir ch
ildre
n at
5 ye
ars o
f age
Dan
ish
Natio
nal B
irth
Coho
rt – c
ohor
t stu
dy
info
rmat
ion
on al
coho
l int
ake
durin
g pre
gnan
cy w
as d
erive
d fro
m th
e 1st
pren
atal
inte
rview
; all
mot
hers
were
sam
pled
in
strat
a defi
ned
by th
eir av
erag
e alc
ohol
inta
ke (0
, 1–4
, 5–8
, ≥ 9
drin
ks/w
eek)
Wec
hsler
Pr
esch
ool a
nd
Prim
ary S
cale
of In
telli
genc
e –
Revis
ed
(WPP
SI-R
)
pare
ntal
educ
atio
n,
mat
erna
l IQ
, mat
erna
l sm
okin
g in
preg
nanc
y, th
e chi
ld’s
age a
t te
sting
, gen
der,
teste
r, m
ater
nal b
inge
drin
king
, ag
e, BM
I, pa
rity,
hom
e env
ironm
ent,
postn
atal
smok
ing i
n th
e hom
e, he
alth
statu
s, an
d in
dica
tors
for h
earin
g an
d vis
ion
impa
irmen
ts
mat
erna
l con
sum
ptio
n of
lo
w to
mod
erat
e qua
ntiti
es
of al
coho
l dur
ing p
regn
ancy
wa
s not
asso
ciate
d wi
th th
e m
ean
IQ sc
ore o
f pre
scho
ol
child
ren
(full-
scale
IQ
OR
= 1.
1, 95
% C
I: 0.5
–2.4;
ve
rbal
IQ O
R =
1.3,
95%
CI:
0.6–2
.8; p
erfo
rman
ce IQ
O
R =
1.2,
95%
CI:
0.6–2
.6)
Falgr
een
Erik
sen
et al
. (2
012)
[35]
Tabl
e 2. E
xpos
ure t
o lo
w an
d m
oder
ate a
lcoho
l lev
els d
urin
g pre
gnan
cy an
d ch
ildre
n ne
urod
evelo
pmen
t – co
nt.
Stud
y pop
ulat
ion
Type
of s
tudy
Expo
sure
info
rmat
ion
Test
used
fo
r cog
nitiv
e m
easu
rem
ent
Conf
ound
ing f
acto
rsRe
sults
Refe
renc
e
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 435
Den
mar
k: 1
628 w
omen
an
d th
eir ch
ildre
n at
5 y
ears
of ag
e
Dan
ish
Natio
nal B
irth
Coho
rt –
coho
rt stu
dy
info
rmat
ion
on al
coho
l int
ake
durin
g pre
gnan
cy w
as d
erive
d fro
m th
e 1st
pren
atal
inte
rview
; all
mot
hers
were
sam
pled
in
strat
a defi
ned
by th
eir av
erag
e alc
ohol
inta
ke (0
, 1–4
, 5–8
, ≥ 9
drin
ks/w
eek)
Wec
hsler
Pr
esch
ool a
nd
Prim
ary S
cale
of In
telli
genc
e –
Revis
ed
(WPP
SI-R
), Te
st of
Eve
ryda
y At
tent
ion
for
Child
ren
at F
ive
(TEA
Ch-5
), Be
havio
r Rat
ing
Inve
ntor
y of
Exec
utive
Fu
nctio
ns
(BRI
EF)
pare
ntal
educ
atio
n,
mat
erna
l IQ
, pre
nata
l/ m
ater
nal s
mok
ing,
the
child
’s ge
nder
, age
at
testi
ng, t
este
r, pa
rity,
mat
erna
l mar
ital s
tatu
s, ag
e, BM
I, pr
enat
al m
ater
nal a
vera
ge n
umbe
r of
drin
ks/w
eek,
hom
e en
viron
men
t, po
stnat
al pa
rent
al sm
okin
g, he
alth
statu
s, he
arin
g and
visio
n ab
ilitie
s
the a
nalys
es sh
owed
no
statis
ticall
y sign
ifica
nt
effe
cts ar
ising
from
aver
age
week
ly alc
ohol
cons
umpt
ion,
eit
her i
ndivi
duall
y or i
n co
mbi
natio
n on
child
’s in
telli
genc
e (m
ean
diffe
renc
e 0.45
, 95%
CI:
1.44–
2.33)
, atte
ntio
n (m
ean
diffe
renc
e 0.01
, 95%
CI:
–0.14
–0.17
and
exec
utive
fu
nctio
n (m
ean
diffe
renc
e 0.8
1, 95
% C
I: –0
.63–2
.24)
Kesm
odel
et
al. (2
012)
[36]
ADV
– ave
rage
dail
y vol
ume (
ADV)
.O
ther
abbr
eviat
ions
as in
Tabl
e 1.
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)436
Tabl
e 3. S
umm
ary o
f the
impa
ct of
pre
nata
l exp
osur
e to
toba
cco
smok
e and
alco
hol o
n ch
ild n
euro
deve
lopm
ent
Out
com
ePr
enat
al ex
posu
relo
w or
mod
erat
e alco
hol d
rinki
ngac
tive s
mok
ing
passi
ve sm
okin
g–
+–
++
Beha
viora
l diffi
culti
es,
poor
er at
tent
ion
func
tions
, and
exec
utive
fu
nctio
ning
, men
tal
prob
lems
Und
erbj
erg e
t al. (
2012
), Sk
oger
bø et
al. (
2012
), O
’Call
agha
n et
al. (
2007
), Ke
lly et
al. (
2010
) [28
–31]
Saya
let al
. (20
07) [
26]
Roza
et al
. (20
09) [
5]M
artin
et al
. (20
06),
Julve
z (20
07),
Mez
zaca
ppa e
t al. (
2011
), Co
rneli
us et
al. (
2011
) [7
,16,19
,20]
–
Dec
reas
ed ch
ild
inte
llige
nce,
cogn
itive
, lan
guag
e and
mot
or
defic
its
Falgr
een
Erik
sen
et al
. (2
012)
, Alat
i et a
l. (20
08),
Kesm
odel
et al
. (20
12)
[34–
36]
How
ell et
al. (
2006
) [33
]Ba
tty et
al. (
2006
), H
uijb
regt
s et a
l. (20
06),
Lawl
or et
al. (
2006
), G
ilman
et al
. (20
08),
Brau
n et
al. (
2009
), Ka
four
i et a
l. (20
09),
Falgr
een
Erik
sen
et al
. (2
012)
, Pol
ansk
a et a
l. (2
013)
[6,8,
9–13
,15]
Julve
z et a
l. (20
07),
Polan
ska e
t al. (
2013
) (fo
r mot
or ab
ilitie
s) [7
,8]
Hsie
h et
al. (
2008
), Je
dryc
hows
ki et
al.
(201
0), L
ee et
al. (
2011
) [2
1–23
]
Poor
er p
erfo
rman
ce at
ve
rbal,
abstr
act/v
isual,
an
d qu
antit
ative
scale
s, m
emor
y
–W
illfo
rd et
al. (
2006
) [27
]H
uijb
regt
s et a
l. (20
06) [
6]Ju
lvez e
t al. (
2007
) [7]
–
Lowe
r sch
ool
achi
evem
ents,
de
crea
sed
learn
ing
abili
ties
O’C
allag
han
et al
. (20
07)
[29]
–La
mbe
et al
. (20
06),
Gilm
an et
al. (
2008
), D
’Ono
frio
et al
. (20
10)
[11,1
7,18]
Mar
tin et
al. (
2006
), O
’Call
agha
n et
al. (
2010
) [1
4,16]
Hsie
h et
al. (
2008
) [21
]
“+” –
stat
istica
lly si
gnifi
cant
asso
ciatio
n be
twee
n th
e exp
osur
e to
mat
erna
l sm
okin
g or d
rinki
ng d
urin
g pre
gnan
cy an
d ch
ild n
euro
deve
lopm
ent;
“–“ –
no
statis
ticall
y sign
ifica
nt as
socia
tion
betw
een
the e
xpos
ure t
o m
ater
nal s
mok
ing o
r drin
king
dur
ing p
regn
ancy
and
child
neu
rode
velo
pmen
t.
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 437
The mechanism of exposure to tobacco and alcohol and children neurodevelopmentThe biological mechanism of exposure to active and pas-sive smoking and alcohol consumption during pregnancy on brain development is well-described.In order to understand mechanisms by which maternal smoking during pregnancy may influence neurodevelop-mental performance, it is necessary to consider the effects of exposure not only to nicotine but to large amounts of other toxic substances including carbon monoxide and components of tar that can directly affect development of the fetal brain and nervous system. Increased level of car-boxyhemoglobin in the bloodstream and reduced uterine blood flow by nicotine results in the fetus being deprived of oxygen and nutrients. Nicotine acts as a stimulant to cholinergic neurons, affecting neuro- and synaptogenesis and apoptosis [37]. Prenatal tobacco smoke exposure has also been linked to changes in amino-acid transportation, protein synthesis and enzyme activity, which can have a lasting impact on the developing brain. Cigarettes also contain many other toxic chemicals, including lead that can affect a developing fetus.The teratogenicity of alcohol has been established [38–41]. This literature shows the importance for outcome of the dose, timing and conditions of exposure, as well as individual sensitivity of both mother and offspring [40]. Ethanol enhances migration of nerve cells, which is hy-pothesized to be involved in behavioral difficulties in child-hood. It also interferes with the production of neuroendo-crine hormones, which may perturb brain growth [41].
Exposure assessmentThe studies evaluating the impact of prenatal tobacco smoke exposure on child neurodevelopment assessed the exposure based on questionnaire data which may not be reliable. Some of the studies collect the data prospec-tively (the birth cohort studies) where exposure level during pregnancy was assessed in each trimester or at least once
established, avoiding alcohol use during pregnancy contin-ues to be the advice for women.
SUMMARY OF THE STUDY RESULTSThe reviewed studies indicate that maternal lifestyle dur-ing pregnancy, like active and passive smoking and alcohol drinking may contribute to neurodevelopmental problems in the offspring.The results of the studies analyzing the association between prenatal exposure to tobacco constituents and children’s neurodevelopment are not consistent. Some of them indi-cated that such exposure is harmful to the developing ner-vous system and established a link between the analyzed exposure and the neurobehavioral abnormalities (or some of them) in both infants and children [7,8,14,16,19,20–23], whereas other studies did not indicate the associa-tion after adjustment for covariates [5,6,9–13,15,17,18]. The association was most consistent for poorer acade-mic achievements and increased risk of behavioral pro blems in children [7,14,16,19,20]. The results of the studies on low or moderate exposure to alcohol are inconsistent. In some of the studies maternal alcohol intake during pregnancy was associated with men-tal health problems [26], and poorer composite score and verbal, abstract/visual and quantitative subscales [27]. On the other hand, no effect on attention, learning, cognitive problems [29] also no increased risk of clinically relevant behavioral difficulties or cognitive deficits [30] and execu-tive functioning was found [31]. Additionally the results of the studies on the impact of low to moderate alcohol consumption on IQ are inconclusive. Lower IQ scores were observed in some [33], but not all studies [34,35].When reviewing the epidemiological studies on the influ-ence of exposure to environmental factors and neurode-velopment in children, it is important to take into account the current limitations of these studies resulting from in-adequacies in exposure and outcome assessment, study design and analysis.
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)438
Preschool and Primary Scale of Intelligence, Wechsler or Wide Range Achievement Test or subscales of these tests [6,11,13,15,19,33–36]. For the evaluation of child be-havior the authors used The Child Behavior Checklist [5,29] or Test of Everyday Attention for Children [28,36].
Confounding factorsThe discussion to control the variables should be evidence-based on the findings reported in context of these relation-ships. The results of the most of presented studies were adjusted for well-known confounders. Those confounders are as follows: maternal and child demographic factors, such as maternal age, race, education, marital status, an-nual household income and child’s gender. Additionally, highly-stimulating home environment may help to counteract negative effects of prenatal tobacco smoke or alcohol exposure, but this was considered only in some of the reviewed studies. In evaluating the im-pact of active maternal smoking on child neurodevelop-ment the maternal ETS exposure and the child postna-tal ETS exposure is recommended to be included as con-founding factors. Other factors that can have an impact on child neurodevelopment are: gestational age, child birth weight and child head circumference.Nearly all studies included in current review accounted for some of the variables stated above, but the concern is gen-erally not that such factors are unmeasured, but that they are not measured well, which is the crucial point for stress, home environment and social class.
Windows of exposureThe effects produced by a neurotoxic agent depend on a number of factors: the timing and duration of expo-sure, the distribution of the toxicant in various parts of the nervous system, the amount or concentration of the agent in nervous tissue, and the ability of a toxi-cant to interfere with specific developmental process-es. Therefore, the neurodevelopmental consequences
during pregnancy, but there are also studies which use ret-rospective report of smoking status which, especially when it is done many years after child birth, may have led to mis-classification. It is also important to remember that smoking habits can change over time with the reduction or quitting smoking during pregnancy, so the single measurement at some point in pregnancy may not indicate a true exposure level [37]. Additionally, women who do not smoke may be exposed to passive smoking which is also linked to a child psychomotor development and should be accounted for.Although the studies on alcohol drinking during preg-nancy and children neurodevelopment are well-designed (prospective cohort), the assessment of exposure is based on the information from mothers which can be the limita-tion of those studies. Alcohol consumption was calculated as the number of glasses of alcoholic drinks consumed weekly. Also, prenatal alcohol use was expressed as the average daily volume (ADV).This review highlights the need for monitoring of active and passive tobacco smoking as well as alcohol consump-tion using biomarkers assessment.
Tests for measuring specific neurodevelopmental effectsTo find a suitable test to measure different endpoints is a very challenging task. The investigator has to choose from a large number of potential endpoints that can be assessed in a prospective study on any given compound or a mixture of compounds to which the fetus or the child may be exposed. The choice of neurobehavioral domains and the tests used to index them should be determined by what is known about the impact of a particular envi-ronmental agent on the development of specific cognitive, neuromotor, and behavioral features. The diversity of test, or subtests used for child neurocognitive development as-sessment is one of the main obstacles to perform the me-ta-analysis of existing results.Most of the studies included in the current review used Wechsler Intelligence Scale for Children, Wechsler
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 439
Differences in the results between the studiesThere are possibly numerous factors contributing to the divergent results between the studies. The various de-velopmental endpoints used may be a possible explanation for the different study results. The choice of covariates for statistical models may also impact the results. Further is-sue is a possibility of concomitant exposure to other neuro-toxicants. Other potential explanations for the differences among studies include the type and timing of exposure, dose, measurement of the exposure or an outcome [42].Studying neurodevelopmental vulnerabilities in children is very difficult. Varying definitions of endpoints, nonspe-cific end points caused by multiple factors, confounders and effect modifiers, and long latency periods between exposures and outcomes complicate attempts to reach de-finitive conclusions through epidemiologic studies.
Challenges for future studiesLong-term studies that follow participants into adoles-cence and early adulthood are essential to assess the full range of neurodevelopmental consequences of exposure to environmental chemicals.Some consensus regarding outcome measures should be reached to allow direct comparisons to be made between studies that measure the same neurobehavioral function. The choice of a given test should be determined by what is known about the impact of a particular compound expo-sure on the development of specific cognitive, neuromotor or behavioral functions.Reliable exposure assessment, using a biomarker, and re-peated measurement of exposure is crucial especially in the case of tobacco smoking or alcohol consumption, for which detrimental health impacts are well established, and for which the self-reported exposure levels may be underestimated. When the influence of confounding fac-tors is possible, these should be taken into account dur-ing the stage of study design and data collection and fi-nally in the statistical analysis. The potential effects of
of exposure to different neurotoxic agents would be expected to vary, depending on the agent, the devel-opmental stages of exposure, and the pattern and du-ration of exposure during those stages. An environ-mental neurotoxic agent may produce impairment in different functional domains, depending on the time of exposure. For example, the same exposure at different points of development could result in an adverse effect on motor systems versus memory or executive func-tions. Similarly, exposures at different concentrations or for different lengths of time could potentially pro-duce differential effects. Therefore, the constellation of observed effects should not be expected to be the same in different children exposed to the same neuro-toxic agent.The study done by Cornelius et al. (2011) indicated that only exposure to maternal smoking in the 1st trimester of pregnancy was associated with some neurodevel-opmental consequences, but it does not appear to be strong evidence of a particular period of pregnancy in which foetus is most vulnerable to tobacco smoke ex-posure [19]. Mezzacappa et al. (2011) also examined whether the association between prenatal tobacco smoke exposure and cognitive functioning was lessened in children of mothers who reported quitting smoking at early stages of pregnancy compared to children whose mothers smoked throughout it [20]. Although the au-thors noticed that quitting smoking at the beginning of pregnancy can be beneficial for child neurodevelop-ment, the further analysis indicated that early quitters tend to be these who smoked fewer cigarettes per day compared to those who continued to smoke. It is thus unclear whether these findings indicate an association with smoking specially during the later stages of preg-nancy or with the amount of exposure in early stages. In the case of prenatal alcohol exposure 1 study indicates that developing brain may be especially vulnerable to such exposure in the 1st trimester of pregnancy [26].
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)440
The findings from this review should be included in guide-lines for gynaecologists/obstetricians as well as healthcare and public health professionals. All efforts should be taken to eliminate tobacco smoke exposure and alcohol consumption during pregnancy to ensure appropriate chil-dren’s development.
REFERENCES
1. Plomin R, Owen M, McGuffin P. The genetic basis of com-plex human behaviors. Science. 1994;264(5166):1733–9, http://dx.doi.org/10.1126/science.8209254.
2. Huizink AC, Mulder EJ. Maternal smoking, drinking or can-nabis use during pregnancy and neurobehavioral and cog-nitive functioning in human offspring. Neurosci Biobehav Rev. 2006;30(1):24–41, http://dx.doi.org/10.1016/j.neubio-rev.2005.04.005.
3. The biology and behavioral basis for smoking-attributable disease. A report of the Surgeon General. Atlanta (GA): Cen-ters for Diseases Control and Prevention; 2010.
4. Eriksen M, Mackay J, Ross H. The Tobacco Atlas. 4th ed. Atlanta (GA): American Cancer Society; New York (NY): World Lung Foundation; 2012 [cited 2012 Mar 20]. Available from: http://www.tobaccoatlas.org.
5. Roza SJ, Verhulst FC, Jaddoe VWV, Steegers EAP, Macken-bach JP, Hofman A, et al. Maternal smoking during pregnan-cy and child behaviour problems: The Generation R Study. Int J Epidemiol. 2009;38(3):680–9, http://dx.doi.org/10.1093/ije/dyn163.
6. Huijbregts S, Séguin J, Zelazo P, Parent S, Japel C, Trem-blay R. Interrelations between maternal smoking dur-ing pregnancy, birth weight and sociodemographic factors in the prediction of early cognitive abilities. Infant Child Dev. 2006;15(6):593–607, http://dx.doi.org/10.1002/icd.480.
7. Julvez J, Ribas-Fitó N, Torrent M, Forns M, Garcia-Este-ban R, Sunyer J. Maternal smoking habits and cognitive de-velopment of children at age 4 years in a population-based birth cohort. Int J Epidemiol. 2007;36(4):825–32, http://dx.doi.org/10.1093/ije/dym107.
confounding factors from exposure to other chemicals in most presented studies are unclear. Also the risk from a mixture, whether acting by similar mechanisms or not, need to be accurately assessed. Additionally, the impact of stress, nutrition and home environment need to be measured and controlled.The studies indicated in this review were mostly carried out in the USA and Europe and further research is need-ed to determine whether these findings would translate to other parts of the world.
CONCLUSIONSThe results of the reviewed studies suggest that expo-sure to active and passive smoking and low/moderate alcohol consumption during pregnancy may affect chil-dren’s neurodevelopment. Exposure to these lifestyle factors can result in a spectrum of adverse outcomes from mental retardation and disability, to more subtle changes in function depending on the agent, timing and target tissue dose.The reviewed studies have continued to show some re-lationship between tobacco smoke exposure, from active or passive maternal smoking during pregnancy, and chil-dren’s psychomotor development, but this relationship is not straightforward. The association is most consistent for measures of academic achievements and behavioral prob-lems but the wide variety of measurements used across dif-ferent studies make it difficult to reconcile differences in findings for neuropsychological abilities.Although the results of the studies on low or moderate exposure to alcohol are not fully consistent, some of them suggest that consumption of alcohol during pregnancy may adversely affect children IQ, mental health, mem-ory, performance at verbal, abstract/visual, and quanti-tative scales. Furthermore, as no safe level of drinking during pregnancy has been established, the most conser-vative advice for women is not to drink alcohol during pregnancy.
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 441
the age of 5. J Pregnancy. 2012;2012:945196, http://dx.doi.org/10.1155/2012/945196.
16. Martin RP, Dombrowski SC, MullisC, Wisenbaker J, Hut-tunen MO. Smoking during pregnancy: Association with childhood temperament, behavior, and academic perfor-mance. J Pediatr Psychol. 2006;31(5):490–500, http://dx.doi.org/10.1093/jpepsy/jsj041.
17. Lambe M, Hultman C, Torrång A, Maccabe J, Cnattingi-us S. Maternal smoking during pregnancy and school per-formance at age 15. Epidemiol. 2006;17(5):524–30, http://dx.doi.org/10.1097/01.ede.0000231561.49208.be.
18. D’Onofrio BM, Singh AL, IliadouA, Lambe M, Hult-man CM, Neiderhiser JM, et al. A quasi-experimental study of maternal smoking during pregnancy and offspring aca-demic achievement. Child Dev. 2010;81(1):80–100, http://dx.doi.org/10.1111/j.1467-8624.2009.01382.x.
19. Cornelius MD, de Genna NM, Leech SL, Willford JA, Gold-schmidt L, Day NL. Effects of prenatal cigarette smoke ex-posure on neurobehavioral outcomes in 10-year-old child-ren of adolescent mothers. Neurotoxicol Teratol. 2011; 33(1):137–44, http://dx.doi.org/10.1016/j.ntt.2010.08.006.
20. Mezzacappa E, Buckner JC, Earls F. Prenatal cigarette exposure and infant learning stimulation as predictors of cognitive control in childhood. Dev Sci. 2011;14(4):881–91, http://dx.doi.org/10.1111/j.1467-7687.2011.01038.x.
21. Hsieh ChJ, Liao HF, Wu KY, Hsieh WS, Su YN, Jeng SF et al. CYP1A1 Ile462Val and GSTT1 modify the ef-fect of cord blood cotinine on neurodevelopment at 2 years of age. Neurotoxicology. 2008;29(5):839–45.
22. Jedrychowski W, Perera FP, Jankowski J, Maugeri U, Mrozek-Budzyn D. Mroz E, et al. Early wheezing pheno-types and cognitive development of 3 years olds. Community-recruited birth cohort. Pediatr Allergy Immunol. 2010;21(3): 550–6, http://dx.doi.org/10.1111/j.1399-3038.2009.00905.x.
23. Lee BE, Hong YCh, Park H, Ha M, Kim JH, Chang N, et al. Secondhand smoke exposure during pregnancy and infan-tile neurodevelopment. Environ Res. 2011;111(4):539–44, http://dx.doi.org/10.1016/j.envres.2011.02.014.
8. Polanska K, Hanke W, Sobala W, Trzcinka-Ochocka M, Li-gocka D, Brzeznicki S, et al. Developmental effects of expo-sures to environmental factors: The Polish Mother and Child Cohort Study. BioMed Res Int. 2013;2013, http://dx.doi.org/10.1155/2013/629716.
9. Batty GD, Der G, Deary IJ. Effect of maternal smoking dur-ing pregnancy on offspring’s cognitive ability: Empirical evi-dence for complete confounding in the US national longitu-dinal survey of youth. Pediatrics. 2006;118(3):943–50, http://dx.doi.org/10.1542/peds.2006-0168.
10. Lawlor DA, Najman JM, Batty GD, O’Callaghan MJ, Williams GM, Bor W. Early life predictors of childhood intelligence: Findings from the Mater-University study of pregnancy and its outcomes. Paediatr Perinat Epide-miol. 2006;20(2):148–62, http://dx.doi.org/10.1111/j.1365-3016.2006.00704.x.
11. Gilman SE, Gardener H, Buka SL. Maternal smok-ing during pregnancy and children’s cognitive and physical development: A causal risk factor? Am J Epi-demiol. 2008;168(5):522–31, http://dx.doi.org/10.1093/aje/kwn175.
12. Braun JM, Daniels JL, Kalkbrenner A, Zimmerman J, Nich-olas JS. The effect of maternal smoking during pregnancy on intellectual disabilities among 8-year-old children. Pae-diatr Perinat Epidemiol. 2009;23(5):482–91, http://dx.doi.org/10.1111/j.1365-3016.2009.01056.x.
13. Kafouri S, Leonard G, Perron M, Richer L, Séguin J, Veil-lette S, et al. Maternal cigarette smoking during pregnancy and cognitive performance in adolescence. Int J Epidemi-ol. 2009;38(1):158–72, http://dx.doi.org/10.1093/ije/dyn250.
14. O’Callaghan FV, Al Mamun A, O’Callaghan M, Alati R, Williams GM, Najman JM. Is smoking in pregnancy an in-dependent predictor of academic difficulties at 14 years of age? A birth cohort study. Early Hum Dev. 2010;86(2): 71–6, http://dx.doi.org/10.1016/j.earlhumdev.2009.12.008.
15. Falgreen Eriksen HL, Kesmodel US, Wimberley T, Un-derbjerg M, Kilburn TR, Mortensen EL. Effects of to-bacco smoking in pregnancy on offspring intelligence at
R E V I E W P A P E R K. POLAŃSKA ET AL.
IJOMEH 2015;28(3)442
in early childhood. Monogr Soc Res Child Dev. 2003;68(3): vii-137.
33. Howell KK, Lynch ME, Platzman KA, Smith GH, Coles CD. Prenatal alcohol exposure and ability, academic achieve-ment, and school functioning in adolescence: A longitudi-nal follow-up. J Pediatr Psychol. 2006;31(1):116–26, http://dx.doi.org/10.1093/jpepsy/jsj029.
34. Alati R, Macleod J, Hickman M, Sayal K, May M, Smith GD, et al. Intrauterine exposure to alcohol and tobac-co use and childhood IQ: Findings from a parental-offspring comparison within the Avon Longitudinal Study of Parents and Children. Pediatr Res. 2008;64(6):659–66, http://dx.doi.org/10.1203/PDR.0b013e318187cc31.
35. Falgreen Eriksen HL, Mortensen EL, Kilburn T, Under-bjerg M, Bertrand J, Støvring H, et al. The effects of low to moderate prenatal alcohol exposure in early pregnancy on IQ in 5-year-old children. BJOG. 2012;119(10):1191– 200, http://dx.doi.org/10.1111/j.1471-0528.2012.03394.x.
36. Kesmodel US, Bertrand J, Støvring H, Skarpness B, Denny CH, Mortensen EL, et al. The effect of different alcohol drinking patterns in early to mid-pregnancy on the child’s intelligence, attention, and executive function. BJOG. 2012;119(10):1180–90, http://dx.doi.org/10.1111/j.1471-0528.2012.03393.x.
37. Clifford A, Lang L, Chen R. Effects of maternal cigarette smoking during pregnancy on cognitive parameters of children and young adults: A literature review. Neurotoxi-col Teratol. 2012;34(6):560–70, http://dx.doi.org/10.1016/ j.ntt.2012.09.004.
38. Randall CL, Ekblad J, Anton RF. Perspectives on the pathophysiology of fetal alcohol syndrome. Al-cohol Clin Exp Res. 1990;14(6):807–12, http://dx.doi.org/10.1111/j.1530-0277.1990.tb01818.x.
39. Schenker S, Becker HC, Randall CL, Phillips DK, Baskin GS, Henderson G. Fetal alcohol syndrome: Cur-rent status of pathogenesis. Alcohol Clin Exp Res. 1990;14(6):635–47, http://dx.doi.org/10.1111/j.1530-0277. 1990.tb01220.x.
24. Jones KL, Smith DW. Recognition of the fetal alcohol syn-drome in early infancy. Lancet. 1973;302(7836):999–1001, http://dx.doi.org/10.1016/S0140-6736(73)91092-1.
25. Jacobson JL, Jacobson SW. Effects of prenatal alcohol exposure on child development. Alcohol Res Health. 2002;26(4):282–6.
26. Sayal K, Heron J, Golding J, Emond A. Prenatal alco-hol exposure and gender differences in childhood mental health problems: A longitudinal population-based study. Pediatrics. 2007;119(2):e426–34, http://dx.doi.org/10.1542/peds.2006-1840.
27. Willford J, Leech S, Day N. Moderate prenatal alcohol ex-posure and cognitive status of children at age 10. Alcohol Clin Exp Res. 2006;30(6):1051–9, http://dx.doi.org/10.1111/j.1530-0277.2006.00119.x.
28. Underbjerg M, Kesmodel US, Landrø NI, Bakketeig L, Grove J, Wimberley T, et al. The effects of low to moderate alcohol consumption and binge drinking in early pregnancy on selective and sustained attention in 5-year-old children. BJOG. 2012;119(10):1211–21, http://dx.doi.org/10.1111/j.1471-0528.2012.03396.x.
29. O’Callaghan FV, O’Callaghan M, Najman JM, Williams GM, Bor W. Prenatal alcohol exposure and attention, learning and intellectual ability at 14 years: A prospective longitudi-nal study. Early Hum Dev. 2007;83(2):115–23, http://dx.doi.org/10.1016/j.earlhumdev.2006.05.011.
30. Kelly YJ, Sacker A, Gray R, Kelly J, Wolke D, Head J, et al. Light drinking during pregnancy: Still no increased risk for socioemotional difficulties or cognitive deficits at 5 years of age? J Epidemiol Community Health. 2012;66(1):41–8, http://dx.doi.org/10.1136/jech.2009.103002.
31. Skogerbø Å, Kesmodel US, Wimberley T, Støvring H, Bertrand J, Landrø NI, et al. The effects of low to mod-erate alcohol consumption and binge drinking in early pregnancy on executive function in 5-year-old children. BJOG. 2012;119(10):1201–10, http://dx.doi.org/10.1111/j.1471-0528.2012.03397.x.
32. Zelazo PD, Müller U, Frye D, Marcovitch S, Argitis G, Boseovski J, et al. The development of executive function
TOBACCO AND ALCOHOL AND CHILD NEURODEVELOPMENT R E V I E W P A P E R
IJOMEH 2015;28(3) 443
42. Mendola P, Selevan SG, Gutter S, Rice D. Environmental factors associated with a spectrum of neurodevelopmental deficits. Ment Retard Dev Disabil Res Rev. 2002;8(3):188–97, http://dx.doi.org/10.1002/mrdd.10033.
40. Sampson PD, Streissguth AP, Bookstein FL, Barr HM. On categorizations in analyses of alcohol teratogenesis. Environ Health Perspect. 2000;108(3):421–8, http://dx.doi.org/10.2307/3454531.
41. Pratt OE. Introduction: What do we know of the mechanisms of alcohol damage in utero? Ciba Found Symp 1984;105:1–7.
This work is available in Open Access model and licensed under a Creative Commons Attribution-NonCommercial 3.0 Poland License – http://creativecommons.org/licenses/by-nc/3.0/pl/deed.en.