the correlation between caffeine intake and smoking in pregnant women against the outcomes fetal...

7/29/2019 The Correlation Between Caffeine Intake and Smoking in Pregnant Women Against the Outcomes Fetal Growth R

1/22

THE CORRELATION BETWEEN CAFFEINE INTAKE AND SMOKING IN

PREGNANT WOMEN AGAINST THE OUTCOMES FETAL

GROWTH RESTRICTION

BY : MIRA SHARASWATI

030.05.148

THE FACULTY OF MEDICINE TRISAKTI UNIVERSITY

JAKARTA, 2008


2/22

CONTENTS

ABSTRACT

INTRODUCTION

CHAPTER I

DEFINITION

PHARMACOLOGY

EFFECT WHEN TAKE IN MODERATION

OVERUSE

CAFFEINE INTOXICATION

CAFFEUNE INTAKE DURING PREGNANCY

CHAPTER II

SMOKING

CHAPTER III

DEFINITION

CAUSES

PATOPHYSIOLOGY

DIAGNOSIS AND SURVEILLANCE

CONCLUSION

REFERENCES


3/22

ABSTRACT

Epidemiologic studies have been unable to conclusively evaluate whether caffeine

intake during pregnancy is associated with reduced birth weight and/or fetal growth

restriction. Of 953 women recruited in early pregnancy in Uppsala County, Sweden, from

1996 to 1998, 873 women delivering liveborn singleton infants were included in the analysis.

Caffeine exposures were ascertained from in-person interviews at 612 and 3234 completed

gestational weeks, and maternal plasma was analyzed for cotinine levels as an indicator of

smoking. Analysis of variance was used to estimate the effect of caffeine on birth weight,

gestational age at delivery, and birth weight ratio after accounting for the effects of other

covariates, such as maternal sociodemographic characteristics, plasma cotinine, and

pregnancy symptoms. 6)

Nowadays, many teenage girls and young women have the habit of smoking .They get

access to the smoking habit because of peer pressure or from their elders .Women continue

their smoking habit during their pregnancy also .This creates lot of hazards to their health and

result in complication.5)

Key words : Caffeine; Smoking; Pregnant women; Fetal Growth Retardation


4/22

INTRODUCTION

Caffeine is the most widely consumed xenobiotic in pregnancy, with the potential to

adversely affect the developing fetoplacentalunit. Maternal caffeine intake has been reported

to be associatedwith a reduction in birth weight, but the precise level of intake above which

the risk is increased remains unknown.Caffeine intake of 300 mg/day has been associated

with fetalgrowth restriction. More controversially,others have shown that maternal caffeine

concentration has aninverse association with birth weight when confounders suchas smoking

were taken into account. In 2001 the Committee on Toxicity of Chemicals in Food, UK, after

a thorough review of the literature, concluded that, although caffeine intake >300 mg/day

might be associated with low birth weight and spontaneous miscarriage, the evidence was

inconclusive.

Possible reasons for these inconsistent outcomes include inaccurate estimation of

caffeine consumption, including an assumption that tea and coffee are the only sources of

caffeine, retrospective assessment of caffeine intake, assessment of association based on

consumption in individual trimesters rather than throughout pregnancy, failure to allow for

individual variations in caffeine metabolism, inadequatecontrol for confounding factors such

as smoking and alcohol consumption, and non-uniformity in defining the primary outcome

measures.

Variations in caffeine metabolic activity have been found to be more closely

associated withfetal growth restriction than have blood caffeine concentration.Therefore, any

comprehensive study of the effects of caffeineon fetal growth must include an assessment of

caffeine metabolism.


5/22

CHAPTER I

CAFFEINE 2)

DEFINITION

Caffeine is a bitter white crystalline xanthine that acts as a psychoactive stimulant

drug and a mild diuretic (speeds up urine production) in humans and other animals. Caffeine

is also called guaranine when found in guarana, mateine when found in mate, and theine

when found in tea; all of these names are synonyms for the same chemical compound.

In humans, caffeine is a central nervous system (CNS) stimulant, having the effect of

temporarily warding off drowsiness and restoring alertness. Beverages containing caffeine,

such as coffee, tea, soft drinks and energy drinks enjoy great popularity. Caffeine is the

world's most widely consumedpsychoactive substance, but unlike most others, it is legal and

unregulated in nearly all jurisdictions. In North America, 90% of adults consume caffeine

daily. The U.S. Food and Drug Administration lists caffeine as a "Multiple Purpose Generally

Recognized as Safe Food Substance". One 2008 study suggested that women consuming 200

milligrams or more of caffeine per day had about twice the miscarriage risk as women who

had none, while another 2008 study found no link between miscarriage and caffeine

consumption.

Tea is another common source of caffeine. Although tea contains more caffeine than

coffee, a typical serving contains much less, as tea is normally brewed much weaker. Besides

strength of the brew, growing conditions, processing techniques and other variables also

affect caffeine content. Certain types of tea may contain somewhat more caffeine than other

teas. Tea contains small amounts of theobromine and slightly higher levels of theophylline
http://en.wikipedia.org/wiki/Xanthinehttp://en.wikipedia.org/wiki/Psychoactivehttp://en.wikipedia.org/wiki/Stimulanthttp://en.wikipedia.org/wiki/Drughttp://en.wikipedia.org/wiki/Diuretichttp://en.wikipedia.org/wiki/Guaranahttp://en.wikipedia.org/wiki/Mate_(beverage)http://en.wikipedia.org/wiki/Teahttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Stimulanthttp://en.wikipedia.org/wiki/Drowsinesshttp://en.wikipedia.org/wiki/Coffeehttp://en.wikipedia.org/wiki/Teahttp://en.wikipedia.org/wiki/Soft_drinkhttp://en.wikipedia.org/wiki/Energy_drinkhttp://en.wikipedia.org/wiki/Psychoactive_substancehttp://en.wikipedia.org/wiki/Teahttp://en.wikipedia.org/wiki/Theobrominehttp://en.wikipedia.org/wiki/Theophyllinehttp://en.wikipedia.org/wiki/Xanthinehttp://en.wikipedia.org/wiki/Psychoactivehttp://en.wikipedia.org/wiki/Stimulanthttp://en.wikipedia.org/wiki/Drughttp://en.wikipedia.org/wiki/Diuretichttp://en.wikipedia.org/wiki/Guaranahttp://en.wikipedia.org/wiki/Mate_(beverage)http://en.wikipedia.org/wiki/Teahttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Stimulanthttp://en.wikipedia.org/wiki/Drowsinesshttp://en.wikipedia.org/wiki/Coffeehttp://en.wikipedia.org/wiki/Teahttp://en.wikipedia.org/wiki/Soft_drinkhttp://en.wikipedia.org/wiki/Energy_drinkhttp://en.wikipedia.org/wiki/Psychoactive_substancehttp://en.wikipedia.org/wiki/Teahttp://en.wikipedia.org/wiki/Theobrominehttp://en.wikipedia.org/wiki/Theophylline


6/22

than coffee. Preparation and many other factors have a significant impact on tea, and color is

a very poor indicator of caffeine content.

Caffeine is also a common ingredient of soft drinks such as cola, originally prepared

from kola nuts. Soft drinks typically contain about 10 to 50 milligrams of caffeine per

serving. Chocolate derived from cocoa contains a small amount of caffeine. The weak

stimulant effect of chocolate may be due to a combination of theobromine and theophylline

as well as caffeine.

Various manufacturers market caffeine tablets, claiming that using caffeine of

pharmaceutical quality improves mental alertness. These effects have been borne out by

research that shows that caffeine use (whether in tablet form or not), results in decreased

fatigue and increased attentiveness. These tablets are used by students studying for their

exams and by people who work or drive for long hours.

PHARMACOLOGY

Caffeine is a central nervous system and metabolic stimulant, and is used both

recreationally and medically to reduce physical fatigue and restore mental alertness when

unusual weakness or drowsiness occurs. Caffeine stimulates the central nervous system first

at the higher levels, resulting in increased alertness and wakefulness, faster and clearer flow

of thought, increased focus, and better general body coordination, and later at the spinal cord

level at higher doses. Once inside the body, it has a complex chemistry, and acts through

several mechanisms as described below.

Caffeine is completely absorbed by the stomach and small intestine within 45 minutes

of ingestion. After ingestion it is distributed throughout all tissues of the body and is

eliminated by first-order kinetics. Caffeine can also be ingested rectally, evidenced by the
http://en.wikipedia.org/wiki/Soft_drinkhttp://en.wikipedia.org/wiki/Colahttp://en.wikipedia.org/wiki/Kola_nuthttp://en.wikipedia.org/wiki/Chocolatehttp://en.wikipedia.org/wiki/Cocoahttp://en.wikipedia.org/wiki/Theobrominehttp://en.wikipedia.org/wiki/Theophyllinehttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Rate_equationhttp://en.wikipedia.org/wiki/Soft_drinkhttp://en.wikipedia.org/wiki/Colahttp://en.wikipedia.org/wiki/Kola_nuthttp://en.wikipedia.org/wiki/Chocolatehttp://en.wikipedia.org/wiki/Cocoahttp://en.wikipedia.org/wiki/Theobrominehttp://en.wikipedia.org/wiki/Theophyllinehttp://en.wikipedia.org/wiki/Central_nervous_systemhttp://en.wikipedia.org/wiki/Rate_equation


7/22

formulation of suppositories of ergotamine tartrate and caffeine (for the relief of migraine)

and chlorobutanol and caffeine (for the treatment of hyperemesis).

The half-life of caffeinethe time required for the body to eliminate one-half of the

total amount of caffeine consumed at a given timevaries widely among individuals

according to such factors as age, liver function, pregnancy, some concurrent medications, and

the level of enzymes in the liver needed for caffeine metabolism. In healthy adults, caffeine's

half-life is approximately 34 hours. In women taking oral contraceptives this is increased to

510 hours, and in pregnant women the half-life is roughly 911 hours. Other factors such as

smoking can shorten caffeine's half-life.

Caffeine is metabolized in the liver by the cytochrome P450 oxidase enzyme system

(specifically, the 1A2 isozyme) into three metabolic dimethylxanthines, which each have

their own effects on the body:

Paraxanthine (84%): Has the effect of increasing lipolysis, leading to elevated glycerol and

free fatty acid levels in theblood plasma.

Theobromine (12%): Dilatesblood vessels and increases urine volume. Theobromine is also

the principal alkaloid in cocoa, and therefore chocolate.

Theophylline (4%): Relaxes smooth muscles of thebronchi, and is used to treat asthma. The

therapeutic dose of theophylline, however, is many times greater than the levels attained from

caffeine metabolism.

Like alcohol and nicotine, caffeine readily crosses the bloodbrain barrier that separates

the bloodstream from the interior of the brain. Once in the brain, the principal mode of action

is as an antagonist of adenosine receptors. The caffeine molecule is structurally similar to

adenosine, and binds to adenosine receptors on the surface of cells without activating them

(an "antagonist" mechanism of action). Therefore, caffeine acts as a competitive inhibitor.
http://en.wikipedia.org/wiki/Biological_half-lifehttp://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/Cytochrome_P450_oxidasehttp://en.wikipedia.org/wiki/CYP1A2http://en.wikipedia.org/wiki/Metabolismhttp://en.wikipedia.org/wiki/Xanthinehttp://en.wikipedia.org/wiki/Paraxanthinehttp://en.wikipedia.org/wiki/Lipolysishttp://en.wikipedia.org/wiki/Glycerolhttp://en.wikipedia.org/wiki/Fatty_acidhttp://en.wikipedia.org/wiki/Blood_plasmahttp://en.wikipedia.org/wiki/Theobrominehttp://en.wikipedia.org/wiki/Blood_vesselhttp://en.wikipedia.org/wiki/Urinehttp://en.wikipedia.org/wiki/Cocoahttp://en.wikipedia.org/wiki/Chocolatehttp://en.wikipedia.org/wiki/Theophyllinehttp://en.wikipedia.org/wiki/Smooth_musclehttp://en.wikipedia.org/wiki/Bronchushttp://en.wikipedia.org/wiki/Asthmahttp://en.wikipedia.org/wiki/Alcoholhttp://en.wikipedia.org/wiki/Nicotinehttp://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrierhttp://en.wikipedia.org/wiki/Receptor_antagonisthttp://en.wikipedia.org/wiki/Adenosine_receptorhttp://en.wikipedia.org/wiki/Adenosinehttp://en.wikipedia.org/wiki/Competitive_inhibitorhttp://en.wikipedia.org/wiki/Biological_half-lifehttp://en.wikipedia.org/wiki/Liverhttp://en.wikipedia.org/wiki/Cytochrome_P450_oxidasehttp://en.wikipedia.org/wiki/CYP1A2http://en.wikipedia.org/wiki/Metabolismhttp://en.wikipedia.org/wiki/Xanthinehttp://en.wikipedia.org/wiki/Paraxanthinehttp://en.wikipedia.org/wiki/Lipolysishttp://en.wikipedia.org/wiki/Glycerolhttp://en.wikipedia.org/wiki/Fatty_acidhttp://en.wikipedia.org/wiki/Blood_plasmahttp://en.wikipedia.org/wiki/Theobrominehttp://en.wikipedia.org/wiki/Blood_vesselhttp://en.wikipedia.org/wiki/Urinehttp://en.wikipedia.org/wiki/Cocoahttp://en.wikipedia.org/wiki/Chocolatehttp://en.wikipedia.org/wiki/Theophyllinehttp://en.wikipedia.org/wiki/Smooth_musclehttp://en.wikipedia.org/wiki/Bronchushttp://en.wikipedia.org/wiki/Asthmahttp://en.wikipedia.org/wiki/Alcoholhttp://en.wikipedia.org/wiki/Nicotinehttp://en.wikipedia.org/wiki/Blood%E2%80%93brain_barrierhttp://en.wikipedia.org/wiki/Receptor_antagonisthttp://en.wikipedia.org/wiki/Adenosine_receptorhttp://en.wikipedia.org/wiki/Adenosinehttp://en.wikipedia.org/wiki/Competitive_inhibitor


8/22

Adenosine is found in every part of the body, because it plays a role in the fundamental

ATP-related energy-metabolizing system, but it has special functions in the brain. There is a

great deal of evidence that brain adenosine concentrations are increased by various types of

metabolic stress (including anoxia and ischemia), and act to protect the brain by suppressing

neural activity, and by increasing blood flow. Thus caffeine, by counteracting adenosine, has

a generally disinhibitory effect on brain activity. Exactly how these effects translate into

EFFECT WHEN TAKE IN MODERATION

The precise amount of caffeine necessary to produce effects varies from person to

person depending on body size and degree of tolerance to caffeine. It takes less than an hour

for caffeine to begin affecting the body and a mild dose wears off in three to four hours.

Consumption of caffeine does not eliminate the need for sleep, it only temporarily reduces

the sensation of being tired.

With these effects, Caffeine citrate has proven to be of short and long term benefit in

treating the breathing disorders of apnea of prematurity and bronchopulmonary displasia in

premature infants. The only short term risk associated with caffeine citrate treatment is a

temporary reduction in weight gain during the therapy, and longer term studies (18 to 21

months) have shown lasting benefits of treatment of premature infants with caffeine.

Because adenosine, in part, serves to regulate blood pressure by causing vasodilation,

the increased effects of adenosine due to caffeine withdrawal cause the blood vessels of the

head to dilate, leading to an excess of blood in the head and causing a headache and nausea.

Reduced catecholamine activity may cause feelings offatigue and drowsiness. A reduction in

serotonin levels when caffeine use is stopped can cause anxiety, irritability, inability to
http://en.wikipedia.org/wiki/ATPhttp://en.wikipedia.org/wiki/Anoxiahttp://en.wikipedia.org/wiki/Ischemiahttp://en.wikipedia.org/wiki/Caffeine_citratehttp://en.wikipedia.org/wiki/Apnea_of_prematurityhttp://en.wikipedia.org/wiki/Premature_birthhttp://en.wikipedia.org/wiki/Vasodilationhttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Catecholaminehttp://en.wikipedia.org/wiki/Fatigue_(physical)http://en.wikipedia.org/wiki/Serotoninhttp://en.wikipedia.org/wiki/ATPhttp://en.wikipedia.org/wiki/Anoxiahttp://en.wikipedia.org/wiki/Ischemiahttp://en.wikipedia.org/wiki/Caffeine_citratehttp://en.wikipedia.org/wiki/Apnea_of_prematurityhttp://en.wikipedia.org/wiki/Premature_birthhttp://en.wikipedia.org/wiki/Vasodilationhttp://en.wikipedia.org/wiki/Headachehttp://en.wikipedia.org/wiki/Nauseahttp://en.wikipedia.org/wiki/Catecholaminehttp://en.wikipedia.org/wiki/Fatigue_(physical)http://en.wikipedia.org/wiki/Serotonin


9/22

concentrate and diminished motivation to initiate or to complete daily tasks; in extreme cases

it may cause mild depression. Together, these effects have come to be known as a "crash".

OVERUSE

In large amounts, and especially over extended periods of time, caffeine can lead to a

condition known as caffeinism. Caffeinism usually combines caffeine dependency with a

wide range of unpleasant physical and mental conditions including nervousness, irritability,

anxiety, tremulousness, muscle twitching (hyperreflexia), insomnia, headaches, respiratory

alkalosis, and heart palpitations. Furthermore, because caffeine increases the production of

stomach acid, high usage over time can lead to peptic ulcers, erosive esophagitis, and

gastroesophageal reflux disease.

CAFFEINE INTOXICATION

An acute overdose of caffeine, usually in excess of about 300 milligrams, dependent

on body weight and level of caffeine tolerance, can result in a state of central nervous system

over-stimulation called caffeine intoxication, colloquially "caffeine jitters". The symptoms of

caffeine intoxication are not unlike overdoses of otherstimulants. It may include restlessness,

nervousness, excitement, insomnia, flushing of the face, increased urination, gastrointestinal

disturbance, muscle twitching, a rambling flow of thought and speech, irritability, irregularor

rapid heart beat, and psychomotor agitation. In cases of much larger overdoses mania,

depression, lapses in judgment, disorientation, disinhibition, delusions, hallucinations,

rhabdomyolysis, orpsychosis may occur.
http://en.wikipedia.org/wiki/Depression_(mood)http://en.wikipedia.org/wiki/Substance_dependencehttp://en.wikipedia.org/wiki/Anxietyhttp://en.wikipedia.org/wiki/Irritabilityhttp://en.wikipedia.org/wiki/Anxietyhttp://en.wikipedia.org/wiki/Tremorhttp://en.wikipedia.org/wiki/Muscle_twitchinghttp://en.wikipedia.org/wiki/Hyperreflexiahttp://en.wikipedia.org/wiki/Insomniahttp://en.wikipedia.org/wiki/Headacheshttp://en.wikipedia.org/wiki/Respiratory_alkalosishttp://en.wikipedia.org/wiki/Respiratory_alkalosishttp://en.wikipedia.org/wiki/Heart_palpitationhttp://en.wikipedia.org/wiki/Peptic_ulcerhttp://en.wikipedia.org/wiki/Esophagitishttp://en.wikipedia.org/wiki/Gastroesophageal_reflux_diseasehttp://en.wikipedia.org/wiki/Stimulantshttp://en.wikipedia.org/wiki/Nervousnesshttp://en.wikipedia.org/wiki/Diuresishttp://en.wikipedia.org/wiki/Gastrointestinal_tracthttp://en.wikipedia.org/wiki/Fasciculationhttp://en.wikipedia.org/wiki/Cardiac_arrhythmiahttp://en.wikipedia.org/wiki/Tachycardiahttp://en.wikipedia.org/wiki/Psychomotor_agitationhttp://en.wikipedia.org/wiki/Maniahttp://en.wikipedia.org/wiki/Depression_(mood)http://en.wikipedia.org/wiki/Disorientationhttp://en.wikipedia.org/wiki/Disinhibitionhttp://en.wikipedia.org/wiki/Delusionshttp://en.wikipedia.org/wiki/Hallucinationshttp://en.wikipedia.org/wiki/Rhabdomyolysishttp://en.wikipedia.org/wiki/Psychosishttp://en.wikipedia.org/wiki/Depression_(mood)http://en.wikipedia.org/wiki/Substance_dependencehttp://en.wikipedia.org/wiki/Anxietyhttp://en.wikipedia.org/wiki/Irritabilityhttp://en.wikipedia.org/wiki/Anxietyhttp://en.wikipedia.org/wiki/Tremorhttp://en.wikipedia.org/wiki/Muscle_twitchinghttp://en.wikipedia.org/wiki/Hyperreflexiahttp://en.wikipedia.org/wiki/Insomniahttp://en.wikipedia.org/wiki/Headacheshttp://en.wikipedia.org/wiki/Respiratory_alkalosishttp://en.wikipedia.org/wiki/Respiratory_alkalosishttp://en.wikipedia.org/wiki/Heart_palpitationhttp://en.wikipedia.org/wiki/Peptic_ulcerhttp://en.wikipedia.org/wiki/Esophagitishttp://en.wikipedia.org/wiki/Gastroesophageal_reflux_diseasehttp://en.wikipedia.org/wiki/Stimulantshttp://en.wikipedia.org/wiki/Nervousnesshttp://en.wikipedia.org/wiki/Diuresishttp://en.wikipedia.org/wiki/Gastrointestinal_tracthttp://en.wikipedia.org/wiki/Fasciculationhttp://en.wikipedia.org/wiki/Cardiac_arrhythmiahttp://en.wikipedia.org/wiki/Tachycardiahttp://en.wikipedia.org/wiki/Psychomotor_agitationhttp://en.wikipedia.org/wiki/Maniahttp://en.wikipedia.org/wiki/Depression_(mood)http://en.wikipedia.org/wiki/Disorientationhttp://en.wikipedia.org/wiki/Disinhibitionhttp://en.wikipedia.org/wiki/Delusionshttp://en.wikipedia.org/wiki/Hallucinationshttp://en.wikipedia.org/wiki/Rhabdomyolysishttp://en.wikipedia.org/wiki/Psychosis


10/22

CAFFEINE INTAKE DURING PREGNANCY

The Food Standards Agency has recommended that pregnant women should limit

their caffeine intake to less than 300 mg of caffeine a day the equivalent of four cups of

coffee a day. A higher intake may be associated with miscarriage.

Dr De-Kun Li of Kaiser Permanente Division of Research, which appears in the

American Journal of Obstetrics and Gynecology, concludes that an intake of 200 milligrams

or more per day, representing two or more cups, "significantly increases the risk of

miscarriage". However, Dr. David Savitz, a professor in community and preventive medicine

at New York's Mount Sinai School of Medicine and lead author of the other new study on the

subject published in the January issue of Epidemiology, found no link between miscarriage

and caffeine consumption.

CHAPTER II

SMOKING 4)
http://en.wikipedia.org/wiki/Food_Standards_Agencyhttp://en.wikipedia.org/wiki/Food_Standards_Agency


11/22

BACKGROUND

` Cigarette smoking is a major preventable cause of disease worldwide, and it is the

major cause of premature death in North America. In 1912, Adler first suggested that

inhalation of cigarette smoke might be a cause of lung cancer. Since then, knowledge about

the adverse health effects of smoking has accumulated. The important causes of mortality are

atherosclerotic vascular disease, cancer, and chronic obstructive pulmonary disease (COPD).

Smoking also can contribute to other diseases, eg, histiocytosis X, respiratory bronchiolitis,

obstructive sleep apnea, idiopathic pneumothorax, low birth weight, and perinatal mortality.

Research investigating why people smoke has shown that smoking behavior is

multifaceted. Factors influencing smoking initiation differ from those of smoking behavior

maintenance. Nicotine dependence, genetic factors, and psychosocial factors influence

maintenance of smoking behavior.

Nicotine meets the criteria of a highly addictive drug. Nicotine is a potent

psychoactive drug that induces euphoria, serves as a reinforcer of its use, and leads to

nicotine withdrawal syndrome when it is absent. As an addictive drug, nicotine has 2 very

potent issues: it is a stimulant and it is also a depressant. It can make affects mood and

performance and is the source of addiction to tobacco.

PATHOPHYSIOLOGY

Nicotine releases hormone noted in the following paragraphs that act on various

receptors in the brain. Nicotine use results in more efficient processing of information and

reduction of fatigue. In addition, nicotine has a sedative action, reduces anxiety, and induces

euphoria. Nicotine effects are related to absolute blood levels and to the rate of increase in

drug concentration at receptors.


12/22

Nicotine stimulates the hypothalamic-pituitary axis; this, in turn, stimulates the

endocrine system. Continually increasing dose levels of nicotine are necessary to maintain

the stimulating effects. With regards to dependence, some experts rank nicotine ahead of

alcohol, cocaine, and heroin. A teenager who smokes as few as 4 cigarettes might develop a

lifelong addiction to nicotine.

Small rapid doses of nicotine produce alertness and arousal, as opposed to long

drawn-out doses, which induce relaxation and sedation. Nicotine has a pronounced effect on

the major stress hormones. Nicotine stimulates hypothalamic corticotropin-releasing factor

(CRF), and it increases levels of endorphins, adrenocorticotropic hormone (ACTH), and

arginine vasopressin in a dose-related manner. Corticosteroids also are released in proportion

to plasma nicotine concentration.

Nicotine alters the bioavailability of dopamine and serotonin and causes a sharp

increase in heart rate and blood pressure. Nicotine acts on brain reward mechanisms,

indirectly through endogenous opioid activity and directly through dopamine pathways.

EPIDEMIOLOGY

United States

In 1965, 52% of men and 34% of women were cigarette smokers. Presently, the incidence

of cigarette smoking has decreased to 28% and 24%, respectively. The incidence of smoking

is highest in blacks, blue-collar workers, less-educated persons, and persons in the lower

socioeconomic strata.

The trend is decreasing in more educated persons. Forty percent of men with less than

12 years of education, 35.9% of high school graduates, and 17.4% of college


13/22

graduates smoke. Of women, 30.7% with less than 12 years of education, 29.6% of

high school graduates, and 15.1% of college graduates smoke.

Economic status also is related to smoking behavior. Of men with an income of

$10,000-20,000 per year, 36.3% smoke, as opposed to 23.2% of men who make

$50,000 or more per year. Of women who had a family income of $20,000 or less per

year, 29.8% smoke, as opposed to 19.5% who make $50,000 or more per year.

In 1983, a comparison was made between white-collar workers, of whom 27.9%

smoked, and blue-collar workers, of whom 42.7% smoked.

Twenty-five percent of pregnant women who smoke quit during pregnancy; yet

80% resume smoking after childbirth.

Recent surveys show that 20% of teenage girls smoke, and 15% of teenage boys

smoke.

International

Worldwide, approximately 1.1 billion people smoke. In China, more than 70% of men

older than 25 years smoke. Smoking is more prevalent in developing countries and is

continuing to increase. Prevalence of smoking in North America is decreasing, currently

approximately 25% of North Americans smoke.

Mortality/Morbidity

The health consequences of this addiction are enormous. Tobacco smoking is

responsible for 1 of every 5 deaths and is the most common cause of cancer-related deaths in

the United States. Children smoke 1.1 billion packs of cigarettes yearly. This accounts for

more than $200 billion in future health care costs.


14/22

Tobacco accounts for more than 85% of all deaths due to lung cancer. Approximately 10

million people in the United States have died from causes attributed to smoking since the

Surgeon General's first report in 1964; 2 million of these were from lung cancer alone.

Furthermore, tobacco also has been identified as the leading cause of emphysema, COPD,

bronchitis, and heart disease.

CLINICAL

History

Nicotine addiction is classified as nicotine use disorder according to the Diagnostic

and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-

TR). The criteria for this diagnosis include any 3 of the following within a 1-year time

span:

o Tolerance to nicotine with decreased effect and increasing dose to obtain same

effect

o Withdrawal symptoms after cessation

o Smoking more than usual

o Persistent desire to smoke despite efforts to decrease intake

o Extensive time spent smoking or purchasing tobacco

o

Postponing work, social, or recreational events in order to smoke

o Continuing to smoke despite health hazards

Nicotine withdrawal is classified as a nicotine-induced disorder according to the

DSM-IV-TR. Symptoms include difficulty concentrating, nervousness, headaches,

weight gain due to increased appetite, decreased heart rate, insomnia, irritability, and

depression. These symptoms peak in the first few days but eventually disappear

within a month.


15/22

Symptoms of nicotine toxicity, otherwise known as acute nicotine poisoning, include

nausea, vomiting, salivation, pallor, abdominal pain, diarrhea, and cold sweat.

A previous history of depression, use of antidepressants in the past, and onset of

depression during previous quit attempts should be obtained.

Physical

Physical effects of nicotine use include increased heart rate, accelerated blood pressure, and

weight loss.

Physical effects of nicotine withdrawal and smoking cessation include weight gain due to

increase in appetite, decreased heart rate, and improvement in the senses of taste and smell.

CHAPTER 3

IUGR3)

DEFINITION


16/22

Intrauterine growth restriction (IUGR) refers to a condition in which a fetus is unable to

achieve its genetically determined potential size. This functional definition seeks to identify a

population of fetuses at risk for modifiable but otherwise poor outcomes. This definition

intentionally excludes of fetuses that are small for gestational age (SGA) but are not

pathologically small. SGA is defined as growth at the 10th or less percentile for weight of all

fetuses at that gestational age. Not all fetuses that are SGA are pathologically growth

restricted and, in fact, may be constitutionally small. Similarly, not all fetuses that have not

met their genetic growth potential are in less than the 10th percentile for estimated fetal

weight (EFW).

CAUSES

Maternal causes of IUGR (adapted from Severi et al, 2000)1 include the following:

Chronic hypertension

Pregnancy-associated hypertension

Cyanotic heart disease

Class F or higherdiabetes

Hemoglobinopathies

Autoimmune disease

Protein-calorie malnutrition

Smoking

Substance abuse

Uterine malformations

Thrombophilias

Prolonged high-altitude exposure

Placental or umbilical cord causes of IUGR include the following:
http://c/Documents%20and%20Settings/Compaq/Desktop/english-3/maternal%20caffeine%20intake/fetal%20growth%20restriction.htm#ref1http://www.emedicine.com/med/topic1106.htmhttp://www.emedicine.com/med/topic3250.htmhttp://www.emedicine.com/med/topic3249.htmhttp://c/Documents%20and%20Settings/Compaq/Desktop/english-3/maternal%20caffeine%20intake/fetal%20growth%20restriction.htm#ref1http://www.emedicine.com/med/topic1106.htmhttp://www.emedicine.com/med/topic3250.htmhttp://www.emedicine.com/med/topic3249.htm


17/22

Twin-to-twin transfusion syndrome

Placental abnormalities

Chronic abruption

Placenta previa

Abnormal cord insertion

Cord anomalies

Multiple gestations

PATOPHYSIOLOGY

IUGR occurs when gas exchange and nutrient delivery to the fetus are not sufficient to allow

it to thrive in utero. This process can occur primarily because of maternal disease causing

decreased oxygen-carrying capacity (eg, cyanotic heart disease, smoking,

hemoglobinopathy), a dysfunctional oxygen delivery system secondary to maternal vascular

disease (eg, diabetes with vascular disease, hypertension, autoimmune disease affecting the

vessels leading to the placenta), or placental damage resulting from maternal disease (eg,

smoking, thrombophilia, various autoimmune diseases).

Evaluation of causative factors for intrinsic disorders leading to poor growth may include a

fetal karyotype, maternal serology for infectious processes, and an environmental exposure

history.

DIAGNOSIS AND SURVEILLANCE

Criteria for diagnosis of IUGR

For most purposes, an EFW at or below the 10th percentile is used to identify fetuses at risk.

Importantly, however, understand that this is not a definitive cutoff for uteroplacental

insufficiency. A certain number of fetuses at or below the 10th percentile may be
http://www.emedicine.com/med/topic3410.htmhttp://www.emedicine.com/med/topic3271.htmhttp://www.emedicine.com/med/topic3410.htmhttp://www.emedicine.com/med/topic3271.htm


18/22

constitutionally small. In these cases, short maternal or paternal height, the neonate's ability

to maintain growth along a standardized curve, and a lack of other signs of uteroplacental

insufficiency (eg, oligohydramnios, abnormal Doppler findings) can be reassuring to the

clinician and parents.

Importantly, review the dating criteria before offering intervention to treat growth restriction

in a fetus. If dates are uncertain or unknown, obtaining a second growth assessment over a 2-

to 4-week interval is important unless strong supportive data or risk factors warrant an

immediate change in management plans.

Screening the fetus for growth restriction

Although no single biometric or Doppler measurement is completely accurate for helping

make or exclude the diagnosis of growth restriction, screening for IUGR is important to

identify at-risk fetuses. Dependent upon the maternal condition associated with IUGR (see

Maternal causes of IUGR) patients may undergo serial sonography during their pregnancies.

An initial scan may be obtained in the middle of the second trimester (at 18-20 wk) to

confirm dates, evaluate for anomalies, and identify multiple gestations. A repeat scan may be

scheduled at 28-32 weeks' gestation to assess fetal growth, evidence of asymmetry, and

stigmata of brain-sparing physiology (eg, oligohydramnios, abnormal Doppler findings).

Screening for IUGR in the general population relies on symphysisfundal height

measurements. This is a routine portion of prenatal care from 20 weeks' until term. Although

recent studies have questioned the accuracy of fundal height measurements, particularly in

obese patients, a discrepancy of greater than 3 cm between observed and expected

measurements may prompt a growth evaluation using ultrasound (Jelks et al). 9 The clinician

should be aware that the sensitivity of fundal height measurement is limited, and he or she
http://c/Documents%20and%20Settings/Compaq/Desktop/english-3/maternal%20caffeine%20intake/fetal%20growth%20restriction.htm#MaternalcausesofIUGRhttp://c/Documents%20and%20Settings/Compaq/Desktop/english-3/maternal%20caffeine%20intake/fetal%20growth%20restriction.htm#ref9http://c/Documents%20and%20Settings/Compaq/Desktop/english-3/maternal%20caffeine%20intake/fetal%20growth%20restriction.htm#MaternalcausesofIUGRhttp://c/Documents%20and%20Settings/Compaq/Desktop/english-3/maternal%20caffeine%20intake/fetal%20growth%20restriction.htm#ref9


19/22

should maintain a heightened awareness for potential growth-restricted fetuses. In an

unselected hospital population, only 26% of fetuses that were SGA were suggested to be

SGA based on clinical examination findings.

Biometry and amniotic fluid volumes

Most ultrasonographic machines report aggregate gestational age measurements and

individual parameters. Assessing individual values is important to identify a fetus that is

growing asymmetrically. In the presence of normal head and femur measurements,

abdominal circumference (AC) measurements of less than 2 standard deviations below the

mean appear to be a reasonable cutoff to consider a fetus asymmetric. Baschat and Weiner

showed that a low AC percentile had the highest sensitivity (98.1%) for diagnosing IUGR

(birth weight


20/22

Umbilical artery Doppler measurement

In normal pregnancies, umbilical artery (UA) resistance shows a continuous decline;

however, this does not occur in fetuses with uteroplacental insufficiency. The most

commonly used measure of gestational agespecific UA resistance is the systolic-to-diastolic

ratio of flow, which changes from a baseline value to an elevated value with worsening

disease. As the insufficiency progresses, end-diastolic velocity is lost and, finally, reversed.

UA Doppler measurements may help the clinician decide whether a small fetus is truly

growth restricted. Baschat and Weiner looked at UA resistance to determine if it can help

improve the accuracy of diagnosing IUGR and help identify a small fetus at risk of chronic

hypoxemia.

Middle cerebral artery Doppler

Fong and colleagues identified 297 singleton pregnancies in which EFW was below the 10th

percentile in anatomically normal fetuses. These investigators studied middle cerebral artery

(MCA), renal artery, and UA Doppler findings. They addressed outcomes, including cesarean

delivery for fetal distress, cord pH less than or equal to 7.10, and Apgar score less than or

equal to 7 at 5 minutes. They concluded that a normal MCA Doppler finding may be useful to

help identify small fetuses that are not likely to have a major adverse outcome with a reported

negative predictive value of 86%.18

Venous Doppler waveforms

Venous Doppler has been measured at the ductus venosus (DV), umbilical vein (UV),

inferior vena cava (IVC), and 7 other sites. This provides information about fetal

cardiovascular and respiratory responses to its intrauterine environment. These measurements
http://c/Documents%20and%20Settings/Compaq/Desktop/english-3/maternal%20caffeine%20intake/fetal%20growth%20restriction.htm#ref18http://c/Documents%20and%20Settings/Compaq/Desktop/english-3/maternal%20caffeine%20intake/fetal%20growth%20restriction.htm#ref18http://c/Documents%20and%20Settings/Compaq/Desktop/english-3/maternal%20caffeine%20intake/fetal%20growth%20restriction.htm#ref18


21/22

have been reported to become consistently abnormal when a fetus is severely compromised,

thus providing evidence in support of an expedited delivery. While the optimal vessel for use

for venous Doppler evaluations has not been identified, the knowledge gained from these

measurements provides additional information for the timing of delivery, especially in

extremely premature (


22/22

lation+AND+between+AND+maternal+AND+caffeine+AND+intake+A

ND+and+AND+fetal+AND+growth)&searchid=1&FIRSTINDEX=0&re

sourcetype=HWCIT

2) http://en.wikipedia.org/wiki/Caffeine

3) http://www.emedicine.com/med/topic3247 .

4) http://www.emedicine.com/med/topic1642.htm

5) http://aje.oxfordjournals.org/cgi/content/abstract/127/2/274

6) http://www.scielo.br/pdf/csp/v14n3/0089.
http://aje.oxfordjournals.org/cgi/content/full/155/5/429?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=(correlation+AND+between+AND+maternal+AND+caffeine+AND+intake+AND+and+AND+fetal+AND+growth)&searchid=1&FIRSTINDEX=0&resourcetype=HWCIThttp://aje.oxfordjournals.org/cgi/content/full/155/5/429?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=(correlation+AND+between+AND+maternal+AND+caffeine+AND+intake+AND+and+AND+fetal+AND+growth)&searchid=1&FIRSTINDEX=0&resourcetype=HWCIThttp://aje.oxfordjournals.org/cgi/content/full/155/5/429?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=(correlation+AND+between+AND+maternal+AND+caffeine+AND+intake+AND+and+AND+fetal+AND+growth)&searchid=1&FIRSTINDEX=0&resourcetype=HWCIThttp://en.wikipedia.org/wiki/Caffeinehttp://www.emedicine.com/med/topic3247http://www.emedicine.com/med/topic1642.htmhttp://aje.oxfordjournals.org/cgi/content/abstract/127/2/274http://www.scielo.br/pdf/csp/v14n3/0089http://aje.oxfordjournals.org/cgi/content/full/155/5/429?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=(correlation+AND+between+AND+maternal+AND+caffeine+AND+intake+AND+and+AND+fetal+AND+growth)&searchid=1&FIRSTINDEX=0&resourcetype=HWCIThttp://aje.oxfordjournals.org/cgi/content/full/155/5/429?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=(correlation+AND+between+AND+maternal+AND+caffeine+AND+intake+AND+and+AND+fetal+AND+growth)&searchid=1&FIRSTINDEX=0&resourcetype=HWCIThttp://en.wikipedia.org/wiki/Caffeinehttp://www.emedicine.com/med/topic3247http://www.emedicine.com/med/topic1642.htmhttp://aje.oxfordjournals.org/cgi/content/abstract/127/2/274http://www.scielo.br/pdf/csp/v14n3/0089