The Correlation Between Caffeine Intake and Smoking in Pregnant Women Against the Outcomes Fetal Growth Restriction

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    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

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    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

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    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

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    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.

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    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
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    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
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    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
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    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
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    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
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    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
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    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.

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    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

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    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.

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    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.

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    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

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    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:

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    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

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    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

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    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

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    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

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    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 (

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    6) http://www.scielo.br/pdf/csp/v14n3/0089.

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