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Ethosuximide is a succinimide anticonvulsant, used mainly in absence seizures. It is sold by Pfizer under the name Zarontin®. more...

Zoledronic acid

Adverse Effects

Central Nervous System


  • drowsiness
  • mental confusion
  • insomnia
  • nervousness
  • headache
  • euphoria
  • ataxia
  • hiccups
  • impaired concentration
  • irritability
  • hyperactivity
  • loss of taste
  • night terrors


  • paranoid psychosis
  • increased libido
  • exacerbation of depression


  • dyspepsia
  • vomiting
  • nausea
  • cramps
  • constipation
  • diarrhea
  • stomach pain
  • loss of appetite
  • weight loss
  • gingival hyperplasia
  • swelling of tongue


  • microscopic hematuria
  • vaginal bleeding


The following can occur with or without bone marrow loss:

  • pancytopenia
  • agranulocytosis
  • leukopenia
  • eosinophilia


  • urticaria
  • systemic lupus erythematosus
  • Stevens-Johnson syndrome
  • hirsutism
  • pruritic erythematous rashes


  • myopia


  • abnormal liver function

Drug Interactions

Valproates can either decrease or increase the levels of ethosuximide; However, combinations of valproates and ethosuximide had a greater Protective Index than either drug alone.

It may elevate serum phenytoin levels.


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Preconception Health Care
From American Family Physician, 6/15/02 by Stephanie C. Brundage

Appropriate preconception health care improves pregnancy outcomes. When started at least one month before conception, folic acid supplements can prevent neural tube defects. Targeted genetic screening and counseling should be offered on the basis of age, ethnic background, or family history. Before conception, women should be screened for human immunodeficiency virus and syphilis infection and begin treatment to prevent the transmission of disease to the fetus. Immunizations against hepatitis B, rubella, and varicella should be completed, if needed. Women should be counseled on ways to prevent infection with toxoplasmosis, cytomegalovirus, and parvovirus B19. Environmental toxins such as cigarette smoke, alcohol, and street drugs, and chemicals such as solvents and pesticides should be avoided. In women with diabetes, it is important to optimize disease control through intensive management before pregnancy. Medications for hypertension, epilepsy, thromboembolism, depression, and anxiety should be reviewed and changed, if necessary, before the patient becomes pregnant. Counseling about exercise, obesity, nutritional deficiencies, and the overuse of vitamins A and D is beneficial. Physicians may also choose to discuss occupational and financial issues related to pregnancy and to screen patients for domestic violence. (Am Fam Physician 2002;65:2507-14,2521-2. Copyright[R] 2002 American Academy of Family Physicians.)

Many women have their first visit for prenatal care at eight weeks of pregnancy or later, yet the period of time before the first prenatal visit carries the most risk to fetal development. A survey(1) of patients in a family practice residency clinic showed that 52 percent of 136 women with a negative pregnancy test had a medical risk that could adversely affect a future pregnancy. Because 40 to 50 percent of pregnancies are unintended,(2) family physicians should consider the potential for pregnancy when writing each prescription. Preconception assessment could be offered to women who request pregnancy testing and family planning advice. Preconception issues could be addressed during work physicals and at follow-up visits for patients with chronic diseases.(3,4) Written materials on preconception health care could be made available in waiting and examination rooms. This article covers various topics that family physicians could include in preconception health care. A comprehensive preconception health care checklist is provided in Table 1.

Genetic Risks

Taking folic acid before conception reduces the incidence of neural tube defects, including spina bifida and anencephaly.(5) The average woman receives about 100 mcg of folic acid per day from fortified breads and grains.(6) Beginning at least one month before conception and continuing through the first three months of pregnancy, women should take a daily vitamin supplement containing at least 400 mcg of folic acid. Higher dosages are indicated for special-risk groups. A dosage of 1 mg per day is recommended for women with diabetes mellitus or epilepsy. Mothers who have given birth to children with neural tube defects should take 4 mg of folic acid per day for subsequent pregnancies.(7)

Many women are postponing child bearing until after age 35 years, which poses a higher risk of medical problems during pregnancy and chromosomal abnormalities in the fetus. Older couples should be counseled about genetic risks and the availability of antenatal testing (amniocentesis and chorionic villus sampling), which may not be options if the first visit for prenatal care is delayed. The risk of infertility also increases with age, rising to 20 percent in couples older than 35 years.(8)

Ethnic background of either partner determines whether prenatal screening should be recommended for sickle cell trait, thalassemias, and Tay-Sachs disease carrier state (Table 2(9)).(10) A family history that is positive for certain diseases, such as cystic fibrosis and congenital hearing loss, indicates the need for additional screening.(11) Carrier screening for cystic fibrosis by linkage DNA analysis is recommended for patients with a family history of the disease in a cousin or closer relative. Recent recommendations propose that cystic fibrosis screening be offered to all white patients.(12) Fifty percent of cases of congenital hearing loss are linked to a single genetic defect in the protein connexin-26. In families with an affected family member, the affected person is usually tested first. If the test is positive, preconception testing can be offered for others in the family. Clinical laboratory tests for connexin-26 (nonsyndromic hearing loss, DFNB1/DFNA3) are available from specialty genetics laboratories.

Congenital Infections

Preconception testing for human immunodeficiency virus (HIV) is important because the Pediatric AIDS Clinical Trials Study Group(10) has shown that treatment with zidovudine (Retrovir) reduces the risk of transmission to the fetus from 25.5 percent to 8.3 percent. Screening should also be performed for syphilis. Earlier treatment of HIV and syphilis decreases the risk of transmission to the fetus.

Women who have not received the hepatitis B vaccine should be considered for immunization if they are at risk of sexually transmitted disease or blood exposure. The vaccine may be given during pregnancy; however, rubella and varicella, which are live-virus vaccines, should be given at least one month before conception.(13)

Toxoplasmosis, cytomegalovirus (CMV), and parvovirus B19 (fifth disease) may cause congenital infections if the mother becomes infected during pregnancy. Currently, no immunizations are available for these infections. Toxoplasmosis is a parasite commonly found in raw meat or cat feces. New owners of cats that go outside are most at risk. Women should be counseled to avoid contact with cat feces in litter boxes, wear gloves while gardening, and avoid eating raw or undercooked meat.(14) CMV exposure is especially risky for child care and health care workers. Persons at risk should wash their hands frequently and use gloves to prevent transmission.(14) Parvovirus B19 is transmitted by prolonged close contact with small children who have the disease in household or child care settings. Serologic testing is possible to document previous immunity but is not routinely recommended for these organisms.(15)

Environmental Toxins

The embryo or fetus is more susceptible to environmental toxins than adults. Drug or chemical exposure causes 3 to 6 percent of anomalies. The timing of the exposure determines the type and severity of anomaly. For example, an exposure before 17 days of fetal life could be lethal. Typically, from days 17 to 56 a toxin can cause a structural anomaly, and after day 56, a functional impairment.(11) Some of the common environmental toxins are listed in Table 3,(11) and the U.S. Food and Drug Administration (FDA) pregnancy risk category of common drugs is provided in Table 4.(16)

Employers are legally required to inform workers of exposures to hazardous substances and to furnish them with Material Safety Data Sheets. In the home, pregnant women should avoid prolonged exposure to pesticides and to solvents such as paint thinners and strippers.(17) Ionizing radiation, including that from exposure to radiography and radioactive materials, is associated with genetic damage when delivered at high levels to the developing embryo.(11) Microwaves, ultrasound, and radio waves are nonionizing and safe.

Smoking increases the risk of miscarriage, low birth weight, perinatal mortality, and attention-deficit disorder in the child.(18) If the mother smokes less than one pack of cigarettes per day, the risk of a low-birth-weight infant increases by 50 percent; with more than one pack per day, the risk increases by 130 percent. If the mother quits smoking by 16 weeks of pregnancy, the risk to the fetus is similar to that of a nonsmoker.(19) The physician can recommend behavioral techniques, support groups, and family help. Nicotine patches or gum may be helpful before conception, but most authorities recommend avoiding them during pregnancy. Bupropion (Zyban) may be used during pregnancy. If the patient cannot stop smoking, the physician should help her set a goal to decrease her number of cigarettes to fewer than 10 per day, because many of the adverse effects are dose related.

Alcohol abuse can cause mental retardation, malformation, growth retardation, miscarriage, and behavioral disorders in infants. The effects are dose related: 19 percent of infants are affected when the mother consumes more than four drinks per day, while 11 percent are affected with two to four drinks per day.(20) Patients should be treated for alcoholism through interventional counseling, usually by referral to a treatment program.

Women using illegal drugs such as cocaine, marijuana, or heroin will need help quitting before pregnancy. Cocaine use is associated with miscarriage, prematurity, growth retardation, and congenital defects. Marijuana can cause prematurity and jitteriness in the neonate. Use of heroin may lead to intrauterine growth restriction, hyperactivity, and severe neonatal withdrawal syndrome.(11) Even a single teaching session about how drug use affects the fetus, along with reinforcement at subsequent visits, usually helps women who only occasionally use drugs. Women who use drugs daily should be referred to a substance abuse treatment program. Periodic urine drug testing may help to encourage abstinence. Women who use heroin should be referred to a supervised withdrawal program to be completed before conception. A methadone maintenance program is an alternative if the patient is unable to complete the withdrawal.(20)

Chronic Illnesses


Women whose diabetes is poorly controlled (defined as glycosylated hemoglobin [HbA1C] levels higher than 8.4 percent) have a 32 percent rate of spontaneous abortion and a sevenfold increased risk of severe fetal anomalies compared with women who have good control. Intensive diabetic management starting before conception should decrease the risk of abortions and congenital anomalies and lessen the complications of pregnancy.(11) Insulin has long been the drug of choice for women with type 1 and type 2 diabetes mellitus during pregnancy. Research on the use of glyburide (Micronase) in patients with gestational diabetes shows promise for a future role of oral agents in women with pre-existing diabetes.(21) Table 5(22,23) lists the goals of the preconception visit for women who have diabetes.


Most patients with chronic hypertension can expect an uncomplicated pregnancy but will require enhanced monitoring for the risks of preeclampsia, renal insufficiency, and fetal growth retardation. Medications should be reviewed for use during pregnancy. Methyldopa (Aldomet) and calcium channel blockers are commonly used during pregnancy. Drugs that should be avoided in the first and second trimesters of pregnancy are angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, and thiazide diuretics, which are associated with congenital defects (Table 4(16)).(11)


Children of mothers with epilepsy have a 4 to 8 percent risk of congenital anomalies, which may be caused by anticonvulsant medication or may be related to an increased genetic risk.(24) The role of hypoxia associated with maternal seizures is unclear. These children also have an increased risk of developing epilepsy. Preconception counseling should include optimizing seizure control, prescribing folic acid supplements, 1 to 4 mg per day, and offering referral to a genetic counselor. When possible, use of multiple anticonvulsants should be avoided. Physicians should aim to use the best single agent for the seizure type at the lowest protective level. There is no single drug of choice. The older agents are classified as FDA pregnancy risk category D (Table 4),(16) and the newer agents are poorly studied. If the patient has been seizure-free for two years or longer, drug discontinuation with a long taper period (three months) may be successful.(25)


Women who have a personal or family history of venous thromboembolism should be offered testing for thrombophilia before pregnancy.(26) Women with a history of a deep venous thrombosis (DVT) have a 7 to 12 percent risk of recurrence during pregnancy.(10) Heparin (in regular or low-molecular-weight form) is indicated for prophylaxis and should be started as early in pregnancy as possible. Women receiving warfarin (Coumadin) as maintenance therapy for DVT should be switched to heparin before conception, because warfarin is teratogenic.


About 10 percent of pregnant women have depression. Tricyclic antidepressants and selective serotonin reuptake inhibitors have not been shown to cause any teratogenic effects and may be used before conception.(27) Withdrawal syndromes can occur in neonates whose mothers are treated with tricyclic antidepressants near the time of delivery. Rarely, maternal use of benzodiazepines has been associated with anomalies such as cleft lip and palate, as well as a withdrawal syndrome in the newborn.(16)

Exercise and Nutrition

Regular moderate exercise is generally beneficial and has not been found to increase the risk of low birth weight or other problems.(28) In the first trimester, hyperthermia related to hot tub use has been associated with increases in congenital anomalies.(29) Pregnant women should limit vigorous exercise to avoid an increase in core body temperature above 38[degrees]C (100.4[degrees]F). They should be adequately hydrated, wear loose clothing, and avoid extreme environmental temperatures.(29)

Obesity and being underweight increase pregnancy risks. Obesity increases the risks of hypertension, preeclampsia, diabetes, and delivering a large infant.(11) Women who are obese should diet before conception and then switch to a maintenance diet of 1,800 calories per day while trying to conceive. Women of average height who weigh less than 120 lb are at risk of amenorrhea, infertility, having a low-birth-weight infant, preterm delivery, and anemia.(11) Low birth weight and prematurity are more related to dietary inadequacy at conception than to weight gain during pregnancy. The diets of women with low-birth-weight infants are often deficient in milk, whole grains, vegetables, and fruits.(30)

Other nutritional problems to watch for include pica, vegetarian diets, and milk intolerance. Pica is usually manifested as cravings for dirt, clay, or starch, and may result in malnourishment and ingestion of toxins and infectious agents. Work-up should include evaluation for anemia and possibly a psychiatric evaluation. If the patient cannot stop the behavior, nutritional counseling can focus on substitutions, such as powdered milk, pudding, or rice.(11) Vegetarians who consume eggs or dairy products usually have no nutritional deficiency; however, strict vegans may have deficiencies in amino acids, zinc, calcium, iron, and vitamins D and B12.(11) Such patients may need to be referred to a nutritionist who can recommend proper food selection and supplementation. Milk intolerance is particularly common among black, Asian, and Native American women and may result in calcium deficiency. These women may be able to tolerate yogurt or cooked cheese. They can also benefit from using lactose-reduced milk, lactase tablets, or calcium supplements.

Overdoses of vitamin A, vitamin D, and caffeine may be toxic. Vitamin A is teratogenic in dosages of 20,000 to 50,000 IU per day.(11) The FDA recommends a limit of 3,000 IU per day. Dosages of vitamin D greater than 1,600 to 2,000 IU per day may cause fetal hypercalcemia and growth retardation.(11) Women should not exceed total dosages of 400 IU per day of vitamin D alone or combined in calcium supplements or multiple vitamins. Consumption of caffeine in amounts up to 300 mg per day (two cups of coffee or six glasses of tea or soda) is considered safe by most authorities. Higher amounts of caffeine may be associated with increased rates of abortion and low birth weight.(31)

Common mineral deficiencies in women of childbearing age include iron and calcium (40 percent of menstruating women have deficient iron stores). A daily prenatal vitamin containing 30 mg of elemental iron is sufficient when combined with a diet that includes meats and other foods high in iron.(11) Before conception, women need 1,200 mg of calcium per day, or the equivalent of a quart of milk or fortified orange juice, or six servings of fortified bread or cereals.

Psychosocial Factors

Domestic violence is reportedly underdiagnosed, and the incidence escalates during pregnancy. Physicians should routinely ask about domestic violence using nonjudgmental questions. Validating the woman's concerns and providing a supportive physician-patient relationship are key factors in helping women to leave a violent relationship.(32) Physicians should offer their patients materials on community resources and the telephone number of the local shelter for battered women.

A couple's readiness for children and the availability of sufficient financial resources should be discussed. Physicians may choose to discuss the effect of pregnancy on the mother's work income. If she has a job that requires prolonged standing,(28) will she be able to transfer to a more sedentary job in the last trimester of pregnancy? How will the family handle the loss of her income if she develops complications that require her to take time off? The couple should be advised to learn about their employers' policies regarding parental leave benefits as well as the maternity coverage of their health insurance plan.(33)

The author thanks Nancy D. Taylor, Ph.D., and Steven T. Eggleston, Pharm.D., B.C.P.S., for technical assistance. The author also thanks colleagues Catherine E. Hunt, M.D., D. Wayne Murphy, M.D., Mary P. Ross, Clinical Nutritionist, Pam S. Snape, M.D., and Thomas Wessel, M.D., for reviewing the manuscript.

The author indicates that she does not have any conflicts of interest. Sources of funding: none reported.

STEPHANIE C. BRUNDAGE, M.D., M.P.H., is currently assistant professor in the Departments of Family Medicine at the Medical University of South Carolina, Charleston, and the University of South Carolina School of Medicine, Columbia. She is director of the Appalachia II Public Health District with the South Carolina Department of Health and Environmental Control, Greenville. Dr. Brundage was previously associate director of the family practice residency program of the Greenville Hospital System, Greenville. She received her medical degree from the University of Miami School of Medicine, Fla., and completed a residency in family practice at the University of Miami affiliated hospitals, Miami. Dr. Brundage completed a master's degree in public health at the University of South Carolina.

Address correspondence to Stephanie C. Brundage, M.D., M.P.H., 200 University Ridge, Greenville, SC 29601 (e-mail: brundasc@dhec.state. Reprints are not available from the author.


(1.) Jack BW, Campanile C, McQuade W, Kogan MD. The negative pregnancy test. An opportunity for preconception care. Arch Fam Med 1995;4:340-5.

(2.) Mayer JP. Unintended childbearing, maternal beliefs, and delay of prenatal care. Birth 1997;24:247-52.

(3.) Swan LL, Apgar BS. Preconceptual obstetric risk assessment and health promotion. Am Fam Physician 1995;51:1875-85,1888-90.

(4.) Jack BW, Culpepper L. Preconception care. J Fam Pract 1991; 32:306-15.

(5.) Botto LD, Moore CA, Khoury MJ, Erickson JD. Neural-tube defects. N Engl J Med 1999;341:1509-19.

(6.) Werler MM, Louik C, Mitchell AA. Achieving a public health recommendation for preventing neural tube defects with folic acid. Am J Public Health 1999;89:1637-40.

(7.) Iqbal MM. Prevention of neural tube defects by periconceptional use of folic acid. Pediatr Rev 2000;21:58-66.

(8.) Harper PS. Practical genetic counselling. 4th ed. Boston: Butterworth-Heinemann, 1993.

(9.) Cowchock FS, Johnson A, Jackson LG. Screening for genetic abnormalities. Infertil Reprod Med Clin North Am 1994;5:177-95.

(10.) Leuzzi RA, Scoles KS. Preconception counseling for the primary care physician. Med Clin North Am 1996;80:337-74.

(11.) Cefalo RC, Moos MK. Preconceptional health promotion. In: Cefalo RC, Moos MK, eds. Preconceptional health care: a practical guide. 2d ed. St. Louis: Mosby, 1995.

(12.) Grody WW, Cutting GR, Klinger KW, Richards CS, Watson MS, Desnick RJ. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Genet Med 2001;3:149-54.

(13.) Revised ACIP recommendation for avoiding pregnancy after receiving a rubella-containing vaccine. MMWR Morb Mortal Wkly Rep 2001;50:1117.

(14.) Piper JM, Wen TS. Perinatal cytomegalovirus and toxoplasmosis: challenges of antepartum therapy. Clin Obstet Gynecol 1999;42: 81-96.

(15.) American College of Obstetricians and Gynecologists. Perinatal viral and parasitic infections. ACOG Practice Bulletin Number 20--September 2000. Obstet Gynecol 2000;96:1-13.

(16.) Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk. 5th ed. Baltimore: Williams & Wilkins, 1998.

(17.) Gjerdingen DK, Fontaine P. Preconception health care: a critical task for family physicians. J Am Board Fam Pract 1991;4:237-50.

(18.) Milberger S, Biederman J, Faraone SV, Chen L, Jones J. Is maternal smoking during pregnancy a risk factor for attention deficit hyperactivity disorder in children? Am J Psychiatry 1996;153: 1138-42.

(19.) Floyd RL, Zahniser SC, Gunter EP, Kendrick JS. Smoking during pregnancy: prevalence, effects, and intervention strategies. Birth 1991;18:48-53.

(20.) American College of Obstetricians and Gynecologists. Substance abuse in pregnancy. ACOG Technical Bulletin Number 195--July 1994 (replaces No. 96, September 1986). Int J Gynaecol Obstet 1994;47:73-80.

(21.) Langer O, Conway DL, Berkus MD, Xenakis EM, Gonzales O. A comparison of glyburide and insulin in women with gestational diabetes mellitus. N Engl J Med 2000;343:1134-8.

(22.) Kitzmiller JL, Buchanan TA, Kjos S, Combs CA, Ratner RE. Pre-conception care of diabetes, congenital malformations, and spontaneous abortions. Diabetes Care 1996;19:514-41.

(23.) American Diabetes Association. Preconception care of women with diabetes. Clinical Diabetes 2000; 18:124-8.

(24.) American College of Obstetricians and Gynecologists. Seizure disorders in pregnancy. ACOG educational bulletin. Number 231--December 1996. Int J Gynaecol Obstet 1997;56:279-86.

(25.) Malone FD, D'Alton ME. Drugs in pregnancy: anticonvulsants. Semin Perinatol 1997;21:114-23.

(26.) American College of Obstetricians and Gynecologists. Thromboembolism in pregnancy. ACOG Practice Bulletin Number 19--August 2000. Obstet Gynecol 2000;96:1-10.

(27.) Wisner KL, Gelenberg AJ, Leonard H, Zarin D, Frank E. Pharmacologic treatment of depression during pregnancy. JAMA 1999; 282:1264-9.

(28.) Reilly K. Nutrition, exercise, work, and sex in pregnancy. Prim Care 2000;27:105-15.

(29.) Exercise during pregnancy and the postpartum period. ACOG Technical Bulletin Number 189--February 1994. Int J Gynaecol Obstet 1994;45:65-70.

(30.) Wynn M, Wynn A. A fertility diet for planning pregnancy. Nutr Health 1995;10:219-38.

(31.) Klebanoff MA, Levine RJ, DerSimonian R, Clemens JD, Wilkins DG. Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion. N Engl J Med 1999;341:1639-44.

(32.) Fry LR. Prenatal screening. Prim Care 2000;27:55-69.

(33.) American College of Obstetricians and Gynecologists. Preconceptional care. ACOG technical bulletin number 205--May 1995. Int J Gynaecol Obstet 1995;50:201-7.

COPYRIGHT 2002 American Academy of Family Physicians
COPYRIGHT 2002 Gale Group

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