Nicotine and pregnancy

Nicotine Use in Pregnant Women
and its Effect on Offspring
Jessica Kozlowski, Pak Kei Chan
Alan Lu, Shunzhi Chang
2014 Nov 25
PHM142 Fall 2014
Coordinator: Dr. Jeffrey Henderson
Instructor: Dr. David Hampson
1. Introduction
 Negative
effects of smoking on mother and fetus:
 Neurobehavioral
 Cardiovascular effects
 Reduced infant birth weight
 Premature delivery
 Infant death
1. Introduction
15-25% of mothers smoking during pregnancy
Majority of women who quit for pregnancy start again
after their child’s birth
45% of fathers smoking at the time of their child’s birth
Why not quit? Start smoking cessation?
- nicotine addiction
Nicotine replacement therapy (NRT) better alternative
for the fetus.
Is it safe?
Minimal human data about effect of direct nicotine
exposure in pregnant women, but a lot about tobacco
smoke exposure.
2. Pharmacokinetics of Nicotine
Clear liquid b.p.247 °C
Small molecule
Mw = 162
Miscible in water
logP = 1.2, amphiphilic
Fast absorption
Cross Blood-brain barrier (10~20s)
and placenta barrier
2. Pharmacokinetics of Nicotine
3. Cigarette Smoking during Pregnancy
- Effects on offspring
Few studies to accurately evaluate effects in
pregnant women using nicotine replacement
therapy (NRT). Most effects studied in rodents.
Short term effects: low birth weight and sudden
infant death syndrome.
Long-term effects:
Neurobehavioral problems.
Obesity and type 2 diabetes.
Respiratory dysfunction.
Childhood cancers (leukemia/lymphoma).
Impaired fertility.
3. Cigarette Smoking during Pregnancy
- Neurobehavioural problems
Attention-deficit hyperactivity disorder, learning
disabilities, behavioral problems, increased anxiety.
In rats, nicotine is a
which compromises
development of
critical neural
10 uM
100 uM
3. Cigarette Smoking during Pregnancy
- Hypertension
Associated with in utero exposure to cigarette
Perinatal nicotine
In rats, perinatal nicotine
Enhances AT1 and attenuates
AT2 gene expression.
Increases Ca2+ sensitivity of
myofilaments leading to
vasoconstriction and
development of hypertensive
phenotype in adulthood.
AT1: Angiotensin II receptor type 1.
AT2: Angiotensin II receptor type 2.
AT1/AT2 ratio ↑
↑ Ca2+ sensitivity of
↑ Vasoconstriction
4. Methods of Smoking Cessation
Bupropion (Zyban)
Nicotine Replacement Therapy
Other (Hypnosis, acupuncture, quitting
gradually, quitting “Cold Turkey”)
4. Preventative Methods
- Bupropion
Initially prescribed to treat various forms of
It was discovered that smoking cravings and
withdrawal effects were reduced.
Inhibition of neurotransmitter uptake
Study conducted showed no increased risk of
congenital malformation in fetal development.
Summary Slide
Nicotine can readily cross the blood-brain barrier and the placental
It is also an ingredient found in tobacco and it’s primary responsible
for sustaining addictive effects.
Smoking during pregnancy has been shown to cause
neurobehavioral and cardiovascular abnormalities.
Nicotine acts as a neuroteratogen and induce neurobehavioral
problems which include: Attention deficit hyperactivity disorder
(ADHD), learning disabilities, or increased risk of nicotine addiction.
An example of a cardiovascular problem is hypertension.
Studies conducted in rats have shown that perinatal nicotine
exposure :
- Alters the gene expression of AT1 and AT2
- Myofilaments are more sensitive to Ca2+
- Vasoconstriction occurs easily, thus causing hypertension
The bottom line:
Absentia > Bupropion > NRT > cigarette smoking, with the best
alternative to smoking being quitting prior to pregnancy.
Thank You
Very Much!
Bruin JE, Gerstein HC, Holloway AC (2010) Long-term consequences of fetal and neonatal nicotine
exposure: a critical review. Toxicol Sci 116: 364-74.
Ho MK, Tyndale RF (2007) Overview of the pharmacogenomics of cigarette smoking.
Pharmacogenomics J 7: 81-98.
Horst WD, Preskorn SH (1998) Mechanisms of action and clinical characteristics of three atypical
antidepressants: venlafaxine, nefazodone, bupropion. J Affect Disord 51: 237-54.
Rose JE, Behm FM, Westman EC, Coleman RE (1999) Arterial nicotine kinetics during cigarette
smoking and intravenous nicotine administration: implications for addiction. Drug Alcohol Depend
56: 99-107.
Slotkin TA (2004) Cholinergic systems in brain development and disruption by neurotoxicants:
nicotine, environmental tobacco smoke, organophosphates. Toxicol Appl Pharmacol 198: 132-51.
Wickstrom R (2007) Effects of nicotine during pregnancy: human and experimental evidence. Curr
Neuropharmacol 5: 213-22.
Wu P, Wilson K, Dimoulas P, Mills EJ (2006) Effectiveness of smoking cessation therapies: a
systematic review and meta-analysis. BMC Public Health 6: 300.
Xiao D, Dasgupta C, Li Y, Huang X, Zhang L (2014) Perinatal nicotine exposure increases
Angiotensin II receptor-mediated vascular contractility in adult offspring. PLoS One 9: e108161.
Zyban 150 mg prolonged release film-coated tablets – Summary of Product Characteristics (SPC)".
electronic Medicines Compendium. GlaxoSmithKline UK. 1 August 2013. Retrieved 22 October

similar documents