Nicotine and Infant Sleep
By Regina Patrick, RPSGT
Physicians encourage pregnant women
who smoke to stop the habit to reduce the
harmful effects of nicotine on an unborn
child (e.g., low birth weight; reduced uterine,
umbilical, and cerebral blood flow).1 Because
the amount of nicotine that an infant ingests
through breastmilk is considered small and
harmless, a physician may not think to caution
a breastfeeding mother to continue refraining
from smoking once a child is born. As a result,
lactating mothers typically resume smoking
soon after delivery. However, some studies
indicate that small amounts of nicotine ingested
through breastmilk can disrupt an infant’s
sleep/wake cycles and increase the risk of
sudden infant death syndrome (SIDS).
to determine an infant’s sleep stage. This is
called indeterminant sleep. Indeterminant sleep
typically occurs during the transition from active
stage R sleep to quiet stage N sleep.
Active sleep is characterized by conjunctive
rapid eye movements, low muscle tone, low
amplitude theta waves, and an irregular
breathing pattern consisting of short central
apneas intermixed with periods of rapid
breathing. Unlike stage R sleep in adults, body
movements may occur during active sleep in
infants. Quiet sleep is characterized by lack
of rapid eye movements, increased muscle
REGINA PATRICK,
RPSGT
tone, a regular breathing pattern, and no body
movements - except for phasic movements
associated with sucking or startles.
Newborn infants first enter active sleep, which is then
followed by quiet sleep. Total sleep time in a newborn
Nicotine & Sleep
consists of 50 percent active sleep and 50 percent
Nicotine is a poisonous alkaloid with a bitter, burning
quiet sleep. At approximately 4 to 6 weeks of age, sleep
taste that is found in tobacco leaves. The most common
spindles (a feature of stage N2 sleep) begin to appear. By
source of nicotine is cigarette smoke. Other sources
approximately 8 to 12 weeks of age, the low-frequency,
of nicotine are snuff, chewing tobacco, and nicotine
high-amplitude waves of slow wave sleep develop. After
patches. At low doses nicotine gives one a sense of
about three months, an infant – like an adult – first enters
alertness and calmness and has a stimulatory effect
stage N sleep (which now consists of stages N1 to N3)
on various organs (e.g., it increases heart rhythm,
followed by stage R sleep.
respiration rate, and gastrointestinal tract motility). At
higher levels, it slows the heart rhythm, respiration rate,
and decreases gastrointestinal tract motility. At toxic
Nicotine & Breastfeeding Infants
levels (60 milligrams or greater), nicotine can cause
A recent study at the Monell Chemical Senses Center
respiratory failure.
in Philadelphia demonstrated the short-term effect of
Nicotine interacts with adrenergic and cholinergic
nicotine on sleep in breastfed infants.6 The study was
receptors in the central nervous system (CNS). Its
headed by Julie Mennella and used 15 mother-infant pairs
interaction with adrenergic neurons alters the release
as subjects. All of the infants’ mothers smoked.
of neurotransmitters that play a role in sleep/wake
Each mother-infant pair was tested on two days. On
cycles. For example, nicotine stimulates the release of
the first test day, the mothers smoked 1 to 3 cigarettes,
dopamine and serotonin in the brain.2-4 Increased levels
but not in the presence of their child. They then
breastfed their infants ad lib during a 3.5-hour period.
of these neurotransmitters in brain regions that control
At the end of this period, the infants took a nap. For the
sleep (e.g., reticular formation) may explain some of
second test day (one week later), the mothers refrained
nicotine’s effect on sleep architecture. Adult smokers
from smoking for 12 hours before breastfeeding their
have a longer latency to sleep, more difficulty in initiating
infant ad lib for the 3.5-hour period, after which the
and maintaining sleep, longer latency to the first period
infants took a nap. On both test days, Mennella and
of rapid eye movement sleep (REM sleep, now called
coworkers measured the amount of nicotine in each
“stage R sleep” in the AASM Manual for the Scoring of
of the mother’s milk before breastfeeding. They also
Sleep and Associated Events), less total sleep time, lower
monitored the infants during their nap for sleep latency,
sleep efficiency, higher percentages of stages N1 sleep
time spent in active and quiet sleep, number of sleep
(formerly “stage 1 sleep”) and N2 sleep (formerly “stage
periods during the nap, longest sleep period, and total
2 sleep”), and a lower percentage of slow-wave sleep.5
sleep time.
Nicotine has a comparable effect on the sleep architecture
The researchers found that on the day the mothers
of infants.
smoked, their breastmilk contained about 12.4
nanograms of nicotine per milliliter of breastmilk and
Infant Sleep
the researchers estimated that the infants were ingesting
An infant’s sleep architecture consists of “quiet” sleep
548.9 nanograms of nicotine per kilogram of the infant’s
and “active” sleep. Active sleep corresponds to adult
body weight. On the day that the mothers did not smoke,
stage R sleep and quiet sleep is the infant’s “stage N
their breastmilk contained about 10.2 nanograms of
sleep” (formerly “non-REM” or “NREM” sleep). At times,
nicotine per milliliter of breastmilk; the researchers
features of both stages can be present making it difficult
22
A2Zzz 2008
• volume 17 • number 1
estimated that the infants ingested 127.1 nanograms of
nicotine per kilogram of the infant’s body weight. They
noted that infants had a 37-percent reduction in total
sleep time when their mothers smoked soon before
breastfeeding. Total sleep time reduction resulted from
two factors: the first being decreased amounts of both
active and quiet sleep and the second, a shortening of the
longest sleep period during the nap. Since refraining from
smoking allowed the infants to have a more normal sleep
architecture, Monnella and coworkers concluded that
nicotine ingested through breastfeeding can have a shortterm, disruptive effect on an infant’s sleep.
Nicotine, CNS & SIDS
Scientists have long noted a higher incidence of SIDS in
infants of mothers who smoke.7 SIDS is the inexplicable,
unexpected death of an apparently healthy infant aged
one year or younger. Some scientists believe SIDS occurs
when hypoxia resulting from apneic episodes during
sleep does not trigger an infant to arouse and start
breathing. This impaired arousability may be the result
of the action of nicotine on CNS structures involved in
respiration, on peripheral chemoreceptors involved in
respiration, or both.
Some studies point to nicotinic receptors in the preBotzinger complex as one CNS site where nicotine may
impact respiration. The pre-Botzinger complex is a small
group of neurons located in the respiratory center in
the lower medulla. The pre-Botzinger complex contains
neurons that are activated only during inspirations
(i.e., inspiratory neurons) and neurons that set one’s
respiratory rhythm (i.e., pacemaker neurons). University
of California, Los Angeles (UCLA) researchers Xuesi Shao
and Jack Feldman found that perfusing nicotine onto
the pre-Botzinger complex can increase the respiration
rate.7 From this they concluded that nicotine may
modulate the function of other neurotransmitters (e.g.,
glutamate) that activate the pre-Botzinger complex
neurons. Other researchers have found that prolonged
overstimulation of nicotinic receptors in brainstem
structures controlling respiration may in turn enhance
the inhibitory actions of peripheral dopaminergic
neurons (e.g., carotid bodies) that modulate the
inspiratory drive.2 The reduction in inspiratory drive
slows the respiration rate and decreases the normal
response (rapid, deep breathing) to hypoxia.
Life-threatening central apneas can occur when
the pre-Botzinger complex is damaged. For example,
Feldman in a 2005 study was surprised to find that
animals in which half the neurons in the pre-Botzinger
complex had been destroyed initially had central apneas
but only during stage R sleep.8 As time progressed over
a 4 to 5 day period, the central apneas began to occur in
stage N sleep and then ultimately when the animals were
awake. He hypothesized that neuronal loss in the preBotzinger complex may play a role in the sudden death
of adults during sleep. Supporting Feldman’s conclusion,
Italian researchers Anna Lavezzi and Luigi Matturri – the
first scientists to identify the pre-Botzinger complex
in humans – noted structural alterations such as
decreased neuronal number and underdevelopment of
the pre-Botzinger complex’s connections to the reticular
formation in infants that have died of SIDS and in
fetuses that die late in gestation.9
Nicotine, Dopamine & SIDS
Nicotine may modulate the actions of dopamine in
the carotid bodies and thereby contribute to SIDS.10
A carotid body is a small neurovascular structure
located on the left and right carotid arteries that
trigger increased respiration rate when stimulated by
hypercapnia (i.e., high blood carbon dioxide level),
hypoxia (i.e., low blood oxygen level), or increased blood
acidity. A carotid body contains type I cells which are
surrounded by type II cells. Swedish researcher Hans
Holgert and coworkers propose that nicotine may
impact dopamine activity in the following way.10 First,
nicotine induces type I cells to release dopamine. The
dopamine may either bind to dopaminergic receptors
on type I cells or bind to dopaminergic receptors on
afferent neurons (i.e., neurons that relay signals to
the brain) that synapse with type I cells. Once bound,
dopaminergic transmission of signals from the carotid
body to the brain is inhibited. This in turn decreases
the respiratory response to hypoxia, which may lead to
apnea and to SIDS.
Conclusions
Nicotine withdrawal can impair an infant’s sleep. If a
mother has smoked throughout her pregnancy, her infant
Continued on page 24...
The AAST wishes to acknowledge and
thank the following organizations for their
gererous support and for investing in the future
of the Sleep Technology Profession as
AAST Supporter Members:
American Association
of Sleep Technologists
American Association
Association
American
of Sleep
Sleep Technologists
Technologists
of
AAST
AAST
2008
2008
Respironics
Cadwell
Laboratories, Inc.
American Association
Association
American
of Sleep
Sleep Technologists
Technologists
of
American Association
Association
American
of Sleep
Sleep Technologists
Technologists
of
AAST
AAST
2008
2008
MVAP Medical
Supplies, Inc.
Cardinal Health
A2Zzz 2008
• volume 17 • number 1
23
Continued from page 23...
may be born addicted to nicotine and begin to suffer
withdrawal symptoms as soon as 12 hours after birth.11
Nicotine withdrawal symptoms in infants can manifest as
crying, irritability, intestinal distress, tremors, muscular
rigidity, and insomnia.6,11,12
Sleep-medicine professionals often fail to ask parents
about an infant’s exposure to nicotine. Staff members at
sleep centers that do infant studies may need to consider
asking parents questions about their infant’s exposure to
nicotine. These questions include:
Does the mother smoke soon before breastfeeding?
Does the mother use nicotine patches or other forms of
nicotine products?
Is the mother a mild, moderate or heavy smoker?
Note that the greater the degree of maternal addiction,
the more disrupted is the infant’s sleep.6 Eliminating passive
nicotine exposure can improve an infant’s sleep, thwart the
miseries of nicotine withdrawal, and reduce the risk of SIDS.
References
1.
Viljoen E. Harmful effects of smoking in pregnancy.
S Afr Med J 2005;95(5):329–330.
2.
Cohen G, Han ZY, Grailhe R et al. Beta-2-nicotinic
acetylcholine receptor subunit modulates protective
responses to stress: a receptor basis for sleepdisordered breathing after nicotine exposure. Proc
Natl Acad Sci U S A 2002;99(20):13272-13277.
3.
Wurtman RJ, Wurtman JJ. Brain serotonin,
carbohydrate-craving, obesity and depression. Obes
Res 1995;3 suppl 4:477S–480S.
4.
Takahashi II, Takada Y, Nagai N et al. Nicotine
increases stress-induced serotonin release by
stimulating nicotinic acetylcholine receptor in rat
striatum. Synapse 1998;28(3):212–219.
5.
Zhang L, Samet J, Caffo B, Punjabi NM. Cigarette
smoking and nocturnal sleep architecture. Am J
Epidemiol 2006;164(6):529–537.
6.
Mennella JA, Yourshaw LM, Morgan LK. Breastfeeding
and smoking: short-term effects on infant feeding and
sleep. Pediatrics 2007;120(3):497–502.
7.
Shao XM, Feldman JL. Mechanisms underlying
regulation of respiratory pattern by nicotine in preBotzinger complex. J Neurophysiol 2001;85(6):2461–
2467.
8.
Schmidt E. UCLA Study links nighttime dying to sleep
apnea from brain cell loss. UCLA Press Release. Aug
8, 2005. Available at: http://newsroom.ucla.edu/
portal/ucla/UCLA-Study-Links-Nighttime-Dying-6348.
aspx?RelNum=6348. Accessed January 8, 2008.
9.
Lavezzi AM, Matturri L. Functional neuroanatomy
of the human pre-Botzinger complex with particular
reference to sudden unexplained perinatal and infant
death. Neuropathology 2007;Nov 20 [Epub ahead of
print].
10.
Holgert H, Hokfelt T, Hertzberg T, Lagercrantz
H. Functional and developmental studies of the
peripheral arterial chemoreceptors in rat: effects of
nicotine and possible relation to sudden infant death
syndrome. Proc Natl Acad Sci U S A 1995;92:7575–
7579.
11.
García-Algar O, Puig C, Vall O et al. Effects of
maternal smoking during pregnancy on newborn
neurobehavior: neonatal nicotine withdrawal
syndrome. Pediatrics 2004;113(3):623-624.
12.
Vagnarelli F, Amarri S, Scaravelli G et al. Neonatal
nicotine withdrawal syndrome in an infant prenatally
and postnatally exposed to heavy cigarette smoke.
Ther Drug Monit 2006;28(5):585–588.
SLEEP TECHS - RECEIVE TRAINING AT
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and meet nationally accepted educational standards.
Complete your training through an A-STEP Provider to:
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A-STEP, the Accredited Sleep Technologist Education Program, is a twostep training initiative endorsed by the AASM. The A-STEP Introductory
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the Introductory Course, A-STEP Self-Study Modules can be completed on
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To learn more, or to enroll, contact
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or visit the AASM Web site, www.aasmnet.org/astep.
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713-827-8896
www.houstonsleepcenter.com
24
A2Zzz 2008
• volume 17 • number 1
Regina Patrick, RPSGT, has been in the sleep field for 22
years, and she currently works as a sleep technologist at St.
Vincent Mercy Sleep Disorders Center in Toledo, Ohio.