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| From
the Editor |
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Editorial
A. Abyad (Chief Editor) |
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Original
Contribution/Clinical Investigation
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<-- Turkey -->
Preoperative
management of sickle cell patients with hydroxyurea
[pdf version]
Mehmet Rami Helvaci,
Sedat Hakimoglu, Mehmet Oktay Sariosmanoglu,
Suleyman Kardas, Beray Bahar, Merve Filoglu,
Ibrahim Ugur Deler, Duygu Alime Almali, Ozcan
Gokpinar, Ozlem Celik, Aynur Ozbay, Ozgun Ilke
Karagoz, Seher Aydin
<-- Ethiopia-->
Khat
(Catha edulis) chewing as a risk factor of low
birth weight among full term Newborns: A systematic
review
[pdf version]
Kalkidan Hassen
<-- Australia -->
Chronic
pain review following Lichtenstein hernia repair:
A Personal Series
[pdf
version]
Maurice Brygel,
Luke Bonato, Sam Farah
<-- Saudi Arabia -->
Assessment
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Saudi Arabia
[pdf
version]
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Hassan M. A. Al-Musa
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Evidence
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| October 2015 -
Volume 13 Issue 7 |
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|
Khat (Catha edulis) chewing
as a risk factor of low birth weight among full
term Newborns: A systematic review
Kalkidan
Hassen
Correspondence:
Kalkidan Hassen (BSc, MSc, PhD fellow),
Assistant Professor
Department of Population and family Health,
College of Health Science,
Jimma University,
Jimma,
Ethiopia
Email: kalkidan.hassen@ju.edu.et
|
Abstract
Introduction:
Chewing the leaves of Khat (chata edulis)
plant has been a custom of people living
in east Africa and the Arabian Peninsula
dating back centuries. Khat has Cathinone,
an amphetamine-like alkaloid which is
responsible for most of documented physiologic
effect. Vasoconstriction in the utero-placental
vascular bed, reduction of placental blood
and myo-endometrial blood flow were among
noted reproductive assaults during pregnancy.
Methods:
The objective of this systematic review
was to synthesize the best available evidence
on association of Khat chewing during
pregnancy and birth weight. Databases
searched were PubMed, CINAHL, PopLine,
LILACS, MedNar and Embase. All papers
selected for inclusion in the review were
subjected to a rigorous appraisal using
standardized critical appraisal. Review
Manager Software (Revman 5.0) was used
for meta-analysis and effect size and
their 95% confidence intervals were calculated.
Result:
On Meta-analysis, data of 1850 neonates
and their maternal history were obtained,
with Khat chewers to non-chewers ratio
of 1.1:1. A mean birth weight of Khat
chewing mothers was found lower than the
non-chewers neonates, with the mean difference
of -130.74 [-189.90, -71.59] grams, Heterogeneity:
Tau² = 0.00; Chi² = 0.95, df
= 1 (P = 0.33); I² = 0%. In all assumptions
tested , the finding of the Meta analysis
has shown consistent direction, while
a reduction of 130.74 grams is the best
available estimate of the effect size.
Conclusion: Khat chewing during
pregnancy is found to be a significant
risk factor for reduction of birth weight
which may contribute a lot to infant mortality.
Key words: Khat chewing, birth
weight, systematic review
|
Khat (Catha edulis) is a plant which grows
wild in countries bordering the Red Sea and
along the east coast of Africa and the Arabian
Peninsula (1). Chewing the leaves of this plant
has been a custom of people living in these
countries dating back centuries. Khat Chewing
in this region has mixed regulatory legislation;
legal in Ethiopia, Djibouti, Kenya, Yemen and
Uganda and illegal in Tanzania and Eritrea (2,
3). Globalization, hammering its restrictions
has helped Khat consumption spread across countries
such as the USA and Western Europe (4, 5). Khat
chewing is common among all segments of the
population, as high as 15% in Ethiopia and 90%
in Yemen (6, 7). According to an Ethiopian national
demographic survey, nearly one in ten Ethiopian
women chew Khat while the corresponding figure
in Yemen is 50% (6, 7). Other studies reported
26% of Ethiopian pregnant women chew Khat, less
compared to Yemenis 41.0% (7-8).
Khat has an active ingredient, Cathinone, an
amphetamine-like alkaloid, responsible for most
of its pharmacological action (10). Additionally,
various phenylalkylamines and considerable amounts
of tannins and flavonoids were also found in
Khat leaves (10-11). Toennes et al., reported
100 grams of Khat leaves contain, 114 mg cathinone,
83 mg cathine and 44 mg norephedrine (12). These
active chemicals induce wider physiological
effects. El-Guindy demonstrated an increase
in temperature and pulse rate as well as mydriasis
in people chewing Khat (13). Urinary retention,
increased sexual desire, impotence and nocturnal
emission, which involves either ejaculation
during sleep for a male or lubrication of the
vagina for a female, are also common with chronic
Khat chewing behavior (13-14). Other studies
on effects associated with Khat chewing reported
sleeplessness, nervousness, nightmares, anorexia,
constipation and inhibition of lactation (13-17).
Effect of Khat on reproductive function is not
optimal. Jansson and colleagues in 1987 noted
vasoconstriction in the utero-placental vascular
bed, impairing foetal growth through reduction
of placental blood flow among pregnant guinea
pigs fed Khat leaves (16). They also showed
an increase in the pressure of uteroplacental
blood by 25% and heart rate by 9% and contrarily
a reduction of Myoendometrial blood flow by
31%. Other studies also reported association
between Khat chewing during pregnancy and reduced
daily food intake, anaemia, and disturbance
of fetal growth, low birth weight, perinatal
and infant death, and other obstetric health
problems (17-22). All the above cocktailed physiologic
effects of Khat are untoward considering the
requirements of the fetus towards optimal maternal
environment for proper growth and fetal development.
Furthermore, the add-on physiologic effect of
Khat on existing stress due to socioeconomic
misfortunes of the region should not be ignored
considering highest infant mortality.
The
objective
of
this
review
was
to
systematically
identify,
appraise
and
synthesize
the
best
available
evidence
on
association
of
Khat
chewing
during
pregnancy
and
birth
weight
of
the
new
born.
Studies
which
include
newborns
of
mothers
who
are
adults
(18
years
old
or
older)
regardless
of
race,
country
of
residence,
Khat
dose,
frequency,
duration
of
chewing
or
other
characteristics
of
Khat
exposure
and
co-presence
of
other
drug
use
were
included.
A
three
staged
search
strategy
was
used
to
identify
all
relevant
published
literature
in
English
language.
Databases
searched
were
PubMed,
CINAHL,
PopLine,
LILACS,
MedNar
and
Embase.
Secondary
search
were
carried
out
from
cross
references
and
finally
gray
literature
were
sought
from
institutions
and
government
websites.
The
search
strategy
used
or
modified
for
the
various
databases
and
search
engines
was
with
initial
keywords/search
terms:
["Catha
edulis"
or
"Khat"
or
"Mairungi"
or
"Miraa"
or
"Qat"]
and
["birth
weight"
or
"low
birth
weight"].
All
papers
selected
for
inclusion
in
the
review
were
subjected
to
a
rigorous,
independent
appraisal
by
the
investigator
prior
to
inclusion
in
the
review
using
standardized
critical
appraisal
instruments
from
the
Joanna
Briggs
Institute
(23).
Quantitative
papers
were
pooled
in
statistical
meta-analysis
using
the
Review
Manager
Software
(Rev
Man
5).
Odds
ratios
and
their
95%
confidence
intervals
were
calculated
for
analysis.
Papers
of
optimal
quality
which
were
selected
for
inclusion
but
without
optimal
data
set
for
meta-analysis
were
subjected
to
narrative
synthesis.
A
total
of
254
relevant
papers
were
identified
in
the
literature
search
and
84
of
them
were
retrieved
for
examination.
Following
review
of
titles
and
abstracts
against
the
review
objectives
and
inclusion
criteria,
69
titles
were
excluded.
The
full
texts
of
the
remaining
16
studies
were
retrieved
for
detailed
evaluation,
after
which,
11
of
these
were
excluded.
The
remaining
7
studies
were
assessed
for
methodological
quality
using
the
JBI-MAStARI
critical
appraisal
tool
and,
subsequently
3
were
excluded;
four
of
them
were
included
in
the
review
for
meta-analysis.
On
Meta-analysis,
data
of
1850
neonates
and
their
mothers
were
obtained,
with
Khat
chewers
to
non-chewers
ratio
of
1.1:1.
Khat
chewing
mothers
had
a
mean
birth
weight
lower
than
the
non-chewers
with
the
mean
difference
of
-346.97
[-670.29,
-23.64].
Click
here
for
Figure
1:
Forest
Plot
including
all
available
relevant
studies,
2015.
The
summary
effect
of
the
Meta
analysis
was
found
to
be
-346.97
[-670.29,
-23.64]
(Heterogeneity:
Tau²
=
103914.69;
Chi²
=
191.95,
df
=
3
(P
<
0.00001);
I²
=
98%).
The
observed
heterogeneity
in
the
meta-analysis
may
not
be
substantial
as
the
researchers
passed
their
critical
appraisal
and
all
have
uniform
direction
of
effect
measure.
However
for
the
statistical
fidelity
sensitivity
analysis
yields
a
better
summary
of
effect,
tested
by
removing
each
study
and
analyzing
the
effect,
accordingly,
removing
the
study
of
Abdurehman
and
Kaima,
2009,
gives
a
summary
effect
with
less
heterogenity
(Heterogeneity:
Tau²
=
19075.18;
Chi²
=
8.93,
df
=
2
(P
=
0.01);
I²
=
78%)
of
-237.77
[-416.99,
-58.55].
Click
here
for
Figure
2:
Forest
Plot
of
the
Meta
analysis
while
removing
a
study
of
'Abdurrahman
and
Keima'
including
all
available
relevant
studies,
2015
Furthermore,
subgroup
analysis
by
year
of
study
(considering
studies
done
before
millennium
development
goal)
gives
a
best
summary
effect
with
heterogeneity
test
equal
to
zero,
(Heterogeneity:
Tau²
=
0.00;
Chi²
=
0.95,
df
=
1
(P
=
0.33);
I²
=
0%).
The
summary
effect
of
the
Meta
analysis
became
-130.74
[-189.90,
-71.59].
Click
here
for
Figure
3:
Subgroup
analysis
considering
studies
before
millennium
development,
2015
With
all
the
assumptions
tested,
the
finding
of
the
Meta
analysis
was
consistent,
neonates
of
Khat
chewing
mothers
had
a
reduced
birth
weight
than
non-chewers
ranging
from
130.74
to
346
grams.
However
considering
heterogeneity,
a
reduction
of
130.74
grams
is
the
best
available
estimate
of
the
effect
size
when
heterogeneity
is
zero.
According
to
WHO,
low
birth
weight
contributes
to
60%
to
80%
of
all
neonatal
deaths.
The
global
prevalence
of
LBW
is
15.5%,
which
amounts
to
about
20
million
Low
birth
weight
infants
born
each
year,
96.5%
of
them
in
developing
countries,
and
most
in
sub-Saharan
countries
where
Khat
chewing
is
also
a
social
custom
(24).
Conventional
risk
factors
of
low
birth
weight
were
well
identified
and
interventions
have
made
lots
of
progress
across
countries,
however,
studies
on
setting
specific
substances
like
Khat
chewing
were
not
studied
well
or
interventions
were
not
yet
popular
or
done
at
all.
The
finding
of
the
Meta
analysis
is
very
crucial
considering
every
gram
which
accounts
for
immediate
and
longer-term
health
and
well-being
of
the
individual
infant
and
has
a
significant
impact
on
neonatal
and
infant
mortality
at
a
population
level.
Furthermore,
the
harm
which
is
induced
on
the
fetus
reflects
the
physiologic
stress
on
the
mother
which
may
hamper
the
capability
of
post-natal
care,
more
specifically
feeding.
Studies
have
shown
Khat
caused
reduction
in
breast
milk
production
and
its
active
substances
passed
through
breast
milk
to
the
infant
(14-17).
The
finding
of
this
review
is
consistent
with
studies
done
on
animal
experiments
intended
to
establish
cause
and
effect
relationship
by
Jansson
et
al.,
who
has
shown
a
reduced
maternal
daily
food
intake
and
maternal
weight
gain
among
Khat
fed
pregnant
guinea
pigs
than
their
controls
(16).
The
study
also
showed,
Khat
feeding
of
the
mother
significantly
reduced
the
mean
birth
weight
of
the
offspring
by
7%
(16).
Another
study
done
by
the
same
authors
to
study
the
Effect
of
Khat
on
utero-placental
blood
flow
in
awake,
chronically
catheterized,
late-pregnant
guinea
pigs
showed
a
reduction
of
blood
flow
by
10%
at
75
min
and
24%
at
180
min
after
Khat
feeding
(25).
Since
randomized
controlled
trials
of
such
studies
on
human
subjects
are
questionable,
such
findings
of
animal
studies
are
helpful
in
postulating
cause
and
effect
relationship,
rather
than
epidemiologic
conclusions.
Studies
on
human
subjects
with
primary
outcome
of
assessing
effect
of
Khat
on
birth
weight
and
or
low
birth
weight
among
human
subjects
are
too
few
or
date
back
decades
considering
the
very
high
custom
of
Khat
chewing
habits
across
residents
of
east
Africa
and
the
Arabian
peninsula.
However,
almost
all
available
studies
describe
the
negative
effect
of
Khat
on
fetal
outcome.
A
study
by
Eriksson
et
al.,
has
shown
non-users
of
Khat,
had
significantly
fewer
low
birth-weight
babies
(less
than
2,500
gram)
compared
to
occasional
users
and
regular
users;
Khat-chewing
mothers
had
more
surviving
children
than
the
non-chewers;
more
children
of
Khat-chewers
had
concomitant
diseases
than
non-chewers
(26).
Similarly,
another
study
reported,
mothers
who
chew
Khat
during
pregnancy
four
times
per
week
were
twice
likely
to
have
fetal
death
compared
to
non-chewers
and
mothers
who
chewed
Khat
during
pregnancy
every
day
were
found
four
times
more
likely
to
have
fetal
death
history
compared
to
non-chewers
(27).
Experience
has
clearly
shown
that
appropriate
care
of
low
birth
weight
infants,
including
their
feeding,
temperature
maintenance,
hygienic
cord
and
skin
care,
and
early
detection
and
treatment
of
infections
and
complications
can
substantially
reduce
mortality
(24).
However,
such
interventions
are
costly
compared
to
primary
prevention
options.
| CONCLUSION
AND
RECOMMENDATION
|
In
this
systematic
review,
Khat
chewing
during
pregnancy
is
found
to
be
a
significant
risk
factor
for
reduction
of
birth
weight
which
may
contribute
high
for
neonatal
mortality.
Thus,
comprehensive
setting
specific
primary
prevention
of
low
birth
weight
should
include
novel
risk
factors
such
as
Khat
chewing
during
pregnancy.
Contemporary
interventions
targeting
Khat
chewing
habit,
incorporating
a
continuum
of
care
including
prevention,
treatment,
and
maintenance
of
pregnant
mothers
should
be
delivered
at
all
levels
of
health
care.
Prevention
measures
designed
for
the
general
population
as
well
as
selectively
for
future
mothers
and
pregnant
women
are
important
in
deterring
the
harmful
effect
of
Khat
on
fetal
birth
weight.
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Kalkidan,
et
al.
"Khat
as
risk
factor
for
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A
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of
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and
Implementation
Reports.
2012;
10.28;
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53-64.
2.
Beckerleg,
S.
What
harm?
Kenyan
and
Ugandan
perspectives
on
khat.
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Affairs.
2006;
105(419):
219-241.
3.
Beckerleg,
S.
Khat
Special
Edition
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&
Misuse,
2008;
43(6):
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KJ:
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6.
Haile,
Demewoz,
and
Yihunie
Lakew.
"Khat
Chewing
Practice
and
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Factors
among
Adults
in
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the
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R.
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use
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Pregnancy:
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sectional
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Middle
East
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Rabat,
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November
14-16,
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9.
Khawaja,
Marwan,
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Al-Nsour,
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