Volume 65, Number 2

OBSTETRICAL AND GYNECOLOGICAL SURVEY

Copyright © 2010
by Lippincott Williams & Wilkins CME REVIEWARTICLE
CHIEF EDITOR’S NOTE: This article is part of a series of continuing education activities in this Journal through which a total
5
of 36 AMA/PRA Category 1 CreditsTM can be earned in 2010. Instructions for how CME credits can be earned appear on the
last page of the Table of Contents.

Preconception Care
Vincenzo Berghella, MD,* Edward Buchanan, MD,†
Leonardo Pereira, MD,‡ and Jason K. Baxter, MD, MSCP§
*Director, Division of Maternal-Fetal Medicine; Director, MFM Fellowship Program, Professor, Department
of Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, PA; †Assistant Professor,
Department of Family and Community Medicine, Thomas Jefferson University, Philadelphia, PA; ‡Director,
Division of Maternal-Fetal Medicine; Associate Professor, Obstetrics and Gynecology, Oregon Health &
Sciences University, Portland, OR; §Director, Division of Research; Associate Professor, Department of
Obstetrics and Gynecology, Thomas Jefferson University, Philadelphia, PA

Our objective was to provide the clinician with easy-to-use evidence-based guidelines, based on the best
available literature, for offering effective preconception care, aimed at decreasing maternal and fetal/
neonatal morbidity and mortality. We searched the Cochrane Library, MEDLINE, and PUBMED from 1966
until January 2009. We used the search terms “preconception,” “preconception care,” “prepregnancy,” and
“inter-pregnancy.” We focused on level I publications, randomized studies, and meta-analyses of these
studies in particular. We included non-English publications, if pertinent. We searched the reference lists of
manuscripts identified, and selected those we judged relevant. Preconception care has been defined as a
set of interventions that aim to identify and modify risks to a woman’s health or pregnancy outcome through
prevention and management. It should occur any time any healthcare provider sees a reproductive age
woman. Personal and family history, physical exam, laboratory screening, reproductive plan, nutrition,
supplements, weight, exercise, vaccinations, and injury prevention should be reviewed in all women. Folic
acid 400 mcg per day, as well as proper diet and exercise should be encouraged. Women should receive the
influenza vaccine if planning pregnancy during flu season; the rubella and varicella vaccines if there’s no
evidence of immunity to these viruses; and tetanus/diphtheria/pertussis if lacking adult vaccination. Specific
interventions to reduce morbidity and mortality for both the woman and her baby should be offered to those
identified with chronic diseases, or exposed to teratogens or illicit substances. There are several interven-
tions that have been proven to effectively improve pregnancy outcome when provided as preconception
care. These should be consistently provided to reproductive-age women.
Target Audience: Obstetricians & Gynecologists, Family Physicians
Leaning Objectives: After completion of this educational activity, the participant should be better able to
assess potential benefits for women and their offspring that result from preconception care, translate specific
evidence-based preconception strategies into clinical practice, and select resources for practitioners and
patients that are print media or online related to preconception health.

Preconception care has ancient origins. Plutarch (46–
120 CE) wrote that the ancient Spartans “[. . .] ordered
Unless otherwise noted below, each faculty’s spouse/life part-
ner (if any) has nothing to disclose.
The authors have disclosed that they have no financial relation-
ships with or interests in any commercial companies pertaining to
this educational activity.
The Faculty and Staff in a position to control the content of
this CME activity have disclosed that they have no financial
relationships with, or financial interests in, any commercial
companies pertaining to this educational activity.
www.obgynsurvey.com | 119
the maidens to exercise [. . .], to the end that the fruit
they conceived might [. . .] take firmer root and find
better growth” (1). Preconception care is a set of inter-
ventions that aim to identify and modify biomedical,
behavioral, and social risks to a woman’s health or
pregnancy outcome through prevention and manage-
ment (2). This care has also been called prepregnancy,
Reprint requests to: Vincenzo Berghella, MD, Division of Maternal-
Fetal Medicine, Department of Obstetrics and Gynecology, Thomas
Jefferson University, 834 Chestnut Street, Suite 400, Philadelphia, PA
19107. E-mail: vincenzo.berghella@jefferson.edu.
120 Obstetrical and Gynecological Survey
or interpregnancy care, or periconceptional medicine
(3). The foundation of preconception care is prevention.
Prevention of disease is the most effective form of
medicine, and health care should shift from the
delivery of procedure-based acute care to the pro-
vision of counseling-based preventive care (4,5).
The first prenatal visit is “months too late!” (6). It
usually happens after first trimester exposure to a
potential teratogen has already occurred. There are
about 1 billion reproductive age (usually defined as
15–44 year old) women worldwide. In the United
States, as an example, only about half of pregnancies
are planned. Therefore, preconception care should
occur any time any healthcare provider sees a repro-
ductive age woman. As women get pregnant later in
life, disease prevalence and medication exposures
increase. Approximately 80% of reproductive age
US women have dental disease, 66% are obese or
overweight, 55% drink alcohol, 11% smoke, 9%
have diabetes, 6% asthma, 3% hypertension, and 3%
cardiac disease (2). The incidences of many of these
conditions, even in pregnant women, are on the rise.
Effectiveness of preventive interventions is best
assessed by randomized trials, so this review focuses
on such level I evidence, where available, as we have
described before (7,8). For example, the 2 leading
causes of death in the first year of life—birth defects
and disorders caused by preterm birth—can both be
significantly reduced by preconception care.
SOURCES AND STUDY SELECTION
We searched the Cochrane Library, MEDLINE,
and PUBMED from 1966 until January 2009. We
used the search terms “preconception,” “preconcep-
tion care,” “prepregnancy,” and “inter-pregnancy.”
We focused, as much as feasible, on randomized
controlled studies, as well as meta-analyses of such
trials. We included non-English publications, if per-
tinent. We searched the reference lists of manuscripts
identified, and selected those we judged relevant.
Review articles and book chapters are cited to pro-
vide readers additional details beyond the scope of
this review.
OPPORTUNITIES FOR PRECONCEPTION
CARE
By age 25, about 50% of US women have had at
least one birth. The highest fertility rate occurs in 25-
to 30-year-old women. By age 44, ⬎85% have give
birth at least once. About 84% of reproductive-age
women, when asked, answer that they had a health-
care visit within the prior year (5). Therefore, uni-
versal preconception care can be achieved if health
care providers make it a priority and plan for it at
every opportunity (Table 1). The approach should be
“every reproductive age woman, every time” (5).
Increased awareness of preconception care should be
accomplished through improved health resources,
public outreach, and advertising.
CONTENT OF PRECONCEPTION CARE
Every reproductive age woman should be asked at
every healthcare encounter: “Are you considering preg-
nancy?” and “Could you possibly become pregnant?”
With these questions to initiate the dialogue, topics
pertinent to optimizing preconception health and there-
fore future maternal and perinatal outcome are dis-
cussed. Topics to be discussed in preconception care are
listed in Table 2 (2,9). We have organized this manu-
script to assist the practitioner, mimicking what would
happen in a real preconception visit; first general health
screening with detection of specific risks, and then
universal as well as individual interventions to optimize
pregnancy outcomes.
TABLE 1
Visits that are opportunities for preconception care
Adolescent (first gynecologic exam)
Any to a doctor during reproductive (15– 44) years
Annual ob-gyn
Postpartum
College—Graduate School health
Family planning, contraception prescribing, and counseling
Pregnancy test (especially if negative)
Health maintenance
Medical work
Emergency visit
Fertility
(Pre-)marriage
TABLE 2
Topics to be reviewed in preconception care
Risk assessment screening
Personal and family history, physical exam, and laboratory
screening
Preventive health
Reproductive plan
Nutrition, supplements, weight, exercise
Vaccinations
Injury prevention
Specific individual issues/“exposures”
Chronic diseases
Medications (teratogens)
Substance abuse/Environmental hazards and toxins
Modified from MMWR Recomm Rep 2006;55(RR-6):1–23 and
Obstet Gynecol 2006;108:1615–1622.
 Preconception Care Y CME Review Article 121

TABLE 3
Cardiovascular risk factors
Preconception screening assessment for all reproductive age
Family history
women (age, 15– 44 yr)
Hypertension
History Dyslipidemia
Reason for visit Obesity
Health status: obstetrical, gynecological, medical, surgical, Diabetes mellitus
and family history Health/risk behaviors
Use of prescription, over-the-counter, complementary and Hygiene (including dental)
alternative medicines Injury prevention
Allergies (to medications or other) Safety belts and helmets
Tobacco, alcohol, other drug use Occupational hazards
Work-related exposures Recreational hazards
Dietary/nutrition assessment Firearms
Physical activity Hearing
Urinary and fecal incontinence Exercise and sports involvement
Physical examination Breast self-examination
Height, weight, body mass index (BMI) Vaccinations
Blood pressure See table 5
Head
*Unless documented immunity.
Neck: adenopathy, thyroid †
HIV screening should be offered as routine to all women of
Breasts
reproductive age, under an “opt-out” policy. Physicians should
Heart, lungs
be aware of and follow their states/countries HIV screening
Abdomen
requirements.
Pelvic examination ‡
Annually or every other year beginning no later than age 21 yr;
Skin
every 2–3 yr after 3 consecutive negative test results if age 30 yr
Laboratory testing
or older with no history of cervical intraepithelial neoplasia 2 or 3,
Rubella titer*
immunosuppression, human immunodeficiency virus (HIV) infec-
Varicella titer*
tion, or diethylstilbestrol exposure in utero.
Human immunodeficiency virus (HIV) testing†
Modified from Obstet Gynecol 2006;108:1615–1622.
Cervical cytology‡
Chlamydia testing (if aged 25 yr or younger and sexually active)
Evaluation and counseling
Sexuality and reproductive planning
High-risk behaviors PRECONCEPTION SCREENING FOR RISK
Discussion of a reproductive health plan
Contraceptive options for prevention of unwanted
ASSESSMENT
pregnancy, including emergency contraception History, Exam, and Laboratory Screen
Genetic counseling
Sexually transmitted diseases Suggested preconception screening assessment is
Partner selection shown in Table 3 (9,10). A questionnaire should be
Barrier protection
Sexual function
completed ahead of time to review this extensive list
Fitness and nutrition (either on paper or online). History should be de-
Dietary/nutrition assessment tailed, especially when pertinent positives are de-
Exercise program tected. Prior inpatient and outpatient medical records
Folic acid supplementation (0.4 mg/d) should be reviewed. Women should be empowered
Calcium intake
Psychosocial evaluation
with easy access to their records (best if electronic), to
Abuse/neglect/violence (physical, sexual, emotional) facilitate multispecialty care coordination. Personal
Sexual practices medical record access is associated with increased ma-
Lifestyle/stress ternal control, satisfaction during pregnancy, and in-
Sleep disorders creased availability of antenatal records during hospital
Home and work (including satisfaction, and environmental
hazards)
attendance (11).
Interpersonal/family relationships; social support Prior obstetrical and gynecological history, includ-
Depression (suicide) ing prior pregnancy complications, should be re-
Criminality viewed. Other reproductive issues should also be
Education assessed: fertility, including the possibility of as-
Language and culture
Health insurance status; coverage; access; public programs
sisted reproductive technology needs; sexuality (in
particular high-risk behaviors); contraception; part-
ner selection; and sexual function. Several social
issues need to be reviewed (Table 3).
122 Obstetrical and Gynecological Survey
All couples should have a basic screen for family
history of heritable genetic disorders, with a pedigree to
at least the second prior generation. Women belonging
to an ethnic group at increased risk for a recessive
condition (Table 4) should be offered appropriate
screening. Cystic fibrosis (CF) screening should be
offered to all couples planning a pregnancy, especially
those who have a family history of CF, or are repro-
ductive partners of individuals with CF (12). Women
with a specific indication for genetic testing should be
referred for formal genetic counseling.
Physical examination details are shown in Table 3.
Pelvic examination may include cytologic and sexually
transmitted infection screening for women with certain
risk factors. Laboratory tests are done routinely (Table
3), and depending on risk factors (Table 4) (9,13).
Universal Preventive Health
Reproductive Health Plan
Asking a reproductive-age woman, and therefore
inducing her to think about, her reproductive health
plan should be a priority of any medical visit (14).
Such a plan should address the desire (or not) for
children, the optimal number, spacing and timing of
pregnancies; contraception to achieve this plan; op-
portunities to improve her health and therefore a
successful reproductive life; and age-related changes
in fertility (14). Having a reproductive health plan
reduces unintended pregnancies, age-related infertil-
ity, and fetal exposure to teratogens (2). Very few
women know that a short interpregnancy interval
(e.g., ⬍6 months from the end of last pregnancy to
the next conception) is associated with increases in
incidences of both small-for-gestational age and low-
birth weight neonates (15). Folic acid depletion may
be the cause for these increased risks (16). Education
and contraception advice are necessary to aim for the
optimal 18 to 24 month interpregnancy interval goal.
All women should be counseled that 2% to 3% of
babies are born with minor (usually) or major anom-
alies. Screening and diagnostic options to detect an-
euploidy and birth defects should be reviewed, and
women should be encouraged to discuss their options
in relation to their personal values.
Nutrition, Weight, and Exercise
Lifelong habits of healthy diet and regular exercise
should be established preconceptionally (17). Proper
diet and exercise can prevent several complications
TABLE 4
Preconception laboratory screening depending on risk factors
Personal history
Age
⬎35: fasting glucose
Race
African American: fasting glucose; hemoglobin
electrophoresis (for sickle cell disease)
Hispanic: fasting glucose
Native American: fasting glucose
Pacific islander: fasting glucose
Mediterranean: mean corpuscular volume (MCV) screening
(for thalassemia)
Ethnic testing: Ashkenazi—familial dysautonomia; Tay-Sachs;
Canavan; Fanconi anemia type C; Niemann-Pick
disease type A; Bloom syndrome; Gaucher; glycogen
storage 1a; Maple syrup urine disease; Mucolipidosis type IV
Prior obstetrical history
Prior birth of a newborn weighting more than 9 lbs or
⬎4500 gm (macrosomia): fasting glucose
History of gestational diabetes mellitus: fasting glucose
Prior unexplained fetal death: check autopsy and karyotype
of fetal death; antiphospholipid antibody testing; fasting
glucose
Prior infant with congenital anomaly (if not screened in that
pregnancy): fasting glucose
Prior recurrent unexplained early pregnancy loss:
antiphospholipid antibody testing; study of uterine
anatomy; parental karyotype
Prior medical history
Metabolic syndrome/obesity; family history of lipid or
coronary disorders: cholesterol/lipid profile
Diabetes: lipid profile, hemoglobin A1c, cardiac and renal
baseline function assessment, ophthalmologic exam
Hypertension: fasting glucose; baseline cardiac, renal, liver
functions
Multiple coronary heart disease risk factors (e.g., tobacco
use, hypertension): lipid profile
High-density lipoprotein cholesterol level less than or equal
to 35 mL/dL: fasting glucose
Triglyceride level greater than or equal to 250 mg/dL:
fasting glucose
History of impaired glucose tolerance or impaired fasting
glucose: fasting glucose
Chronic use of steroids: fasting glucose
Polycystic ovary syndrome: fasting glucose
History of vascular disease: fasting glucose
Marfan syndrome: echocardiogram for assessment of aortic
root; eye exam for lens
History of STD, drug abuse, etc.; HIV, Hep C
Recipients of blood from donors who later tested positive
for HCV infection: Hep C
Recipients of blood or blood-component transfusion or
organ transplant before July 1992: Hep C
Recipients of clotting factor concentrates before 1987: Hep C
Chronic (long-term) hemodialysis: Hep C
History of transfusion from 1978 to 1985: HIV
Invasive cervical cancer: HIV
HIV infection: STD screening; PPD
Medical risk factors known to increase risk of tuberculosis if
infected: PPD
Not sure if had varicella infection in past: varicella titer
(continued)
 Preconception Care Y CME Review Article
TABLE 4
Continued
Social history
HIV or TB contact, IV drug use, etc.: TB testing
History of injecting illegal drugs: HC; HIV; STD screening
(Chlamydia, Gonorrhea, syphilis, etc.); PPD
Occupational percutaneous or mucosal exposure to
HCV-positive blood: Hep C
More than one sexual partner since most recent HIV test or
a sex partner with more than one sexual partner since
most recent HIV test: HIV
Seeking treatment for STDs: HIV
History of prostitution: STD screening, HIV
Past or present sexual partner who is HIV positive or
bisexual or injects drugs: HIV
Long-term residence or birth in an area with high
prevalence of HIV infection: HIV
Adolescents who are or ever have been sexually active: HIV
Adolescents entering detention facilities: HIV; STD screening
Offer to women seeking preconception evaluation: HIV (all
women should be screened)
History of multiple sexual partners or a sexual partner with
multiple contacts: STD screening
Sexual contact with individuals with culture-proven STD:
STD screening
History of repeated episodes of STDs: STD screening
Attendance at clinics for STDs: STD screening
All sexually active women aged 25 yr or younger: chlamydia
All sexually active adolescents: gonorrhea
Close contact with individuals known or suspected to have
tuberculosis: PPD
Born in country with high tuberculosis prevalence: PPD
Medically underserved: PPD
Low income: PPD
Alcoholism: PPD
Resident of long-term care facility (e.g., correctional institu-
tions, mental institutions, nursing homes and facilities): PPD
Health professional working in high-risk health care
facilities: PPD
Family history
Family history of diabetes mellitus: fasting glucose
Family history of diabetes; history of gestational diabetes,
overweight/obese, hypertension, high-risk ethnic group
(Afro-American, Hispanic, Native American): fasting
glucose every 3 yr
Family history suggestive of familial hyperlipidemia: lipid
profile
Family history of premature (age younger than 50 yr for
men, age younger than 60 yr for women) cardiovascular
disease: lipid profile
Colorectal cancer or adenomatous polyps in first-degree
relative younger than 60 yr or in 2 or more first-degree
relatives of any ages; family history of familial
adenomatous polyposis or hereditary nonpolyposis colon
cancer: colonoscopy
First-degree relative (i.e., mother, sister, or daughter) or
multiple other relatives who have a history of
premenopausal breast or breast or ovarian cancer:
mammography
Family history of Marfan syndrome: echocardiogram for
assessment of aortic root; eye exam for lens
Family history of breast cancer: mammography
Family history of thyroid disease: TSH
123
Physical examination
Overweight (BMI ⱖ25): fasting glucose
Hypertension: fasting glucose
Laboratory screening
Persistently abnormal alanine aminotransferase levels: Hep C
Glycosuria: fasting glucose
Hep C indicates hepatitis C; HIV, human immunodeficiency
syndrome; PPD, purified protein derivative; STDs, sexually trans-
mitted diseases.
Modified from Obstet Gynecol 2006;108:1615–1622.
of pregnancy, including gestational diabetes, hyper-
tensive complications, etc (18). Some general pre-
conception “common sense” nutritional advice
includes thoroughly cooking all meat (beef, pork, or
poultry) as well as seafood and shellfish, eating at
least 12 ounces of fish weekly but avoiding ⬎2
serving/wk of shark, swordfish, King mackerel, or
tilefish, all of which contain high concentrations of
mercury. Albacore (white) tuna has more mercury
than canned, light tuna (19). Other recommendations
include eating only pasteurized eggs and dairy prod-
ucts, washing raw fruits and vegetables before eating,
and obtaining a minimum daily iodine intake of 150
mcg/d. Education about proper hand, food, and cook-
ing utensil hygiene is important, especially in devel-
oping countries.
Body mass index (BMI) should be calculated at
least annually for reproductive-age women (20). For
women whose BMI falls outside the normal range
(19–25), preconception counseling is extremely im-
portant. Women with low BMI should be screened
for anorrhexia nervosa or bulimia. Overweight or
obese women should have formal nutritional coun-
seling, and should aim to not get pregnant until
optimal weight is achieved through preconception
exercise and proper nutrition. Calorie and portion-
size control may be the most effective methods of
sustained preconception weight loss. Postpartum in-
dividual counseling on diet and physical activity
increased the proportion of women returning to
prepregnancy weight from 30% to 50% in 1 random-
ized trial (21). An exercise routine that can be started
preconceptionally and safely continued in pregnancy
may include yoga; brisk walking (including hiking
and backpacking); jogging; swimming; biking; cross-
country skiing; and using fitness equipment such as
an elliptical trainer, treadmill, or stationary bike.
Women should be given standard advice for engag-
ing in regular physical activity for 30 to 60 minutes
per day for 5 or more days per week.
124 Obstetrical and Gynecological Survey
Supplements
The preconception intervention with the most
evidence-based data to support its efficacy is folic
acid supplementation. Folic acid supplementation is
recommended, with a minimum of 400 mcg/d for all
women (93% decrease in neural tube defects
[NTDs]), and 4 mg/d for women with prior children
with NTDs (69% decrease in recurrent NTDs) (22).
Supplementation should start at least one month
before conception and continue until at least 28 days
after conception (time of neural tube closure). Given
the unpredictability of planned conception, all repro-
ductive age women should be on folic acid supple-
mentation from menarche to menopause. Women
taking antiseizure medications, other drugs that
might interfere with folic acid metabolism, those
with homozygous methylenetetrahydrofolate reduc-
tase enzyme mutations, or those who are obese, may
need higher doses of folic acid supplementation. As
increases in baseline serum folate level are directly
proportional with a decrease in the incidence of
NTD, some experts have advocated 5 mg of folic
acid per day as optimal universal supplementation
(23). Folic acid supplementation may decrease the
risk of congenital anomalies other than NTDs (e.g.,
cardiac, facial clefts) (24).
The overall benefits or risks of fortifying basic
foods such as grains with added folate has been
associated with a 140 to 200 mcg/d increase in sup-
plementation, and a 20% to 50% decrease in inci-
dence of NTD (25). Education with provision of
printed material (22,26), computerized counseling
(27), and learner-centered nutrition education (28),
all increase the awareness of the folate/neural tube
defects association, and the use of the folate supple-
ments. These interventions may be effective in
increasing the prophylactic use of additional precon-
ception care activities.
There is insufficient evidence to justify the routine
use of other supplements in reproductive age women,
except if a nutritional deficiency has been identified.
The use of certain supplements may be detrimental,
especially if excessive amounts of lipid-soluble vita-
mins such as vitamin A (⬎10,000 IU/d) are taken,
since they can be teratogenic. All supplements, in-
cluding alternative and complementary medicines,
should be reviewed.
Vaccines
Preconception vaccination for the prevention of
fetal and maternal disease is an important preconcep-
tion intervention (Table 5). Maternal immunity to
TABLE 5
Recommended preconception vaccinations
All reproductive age women
Planned pregnancy during flu season: influenza
No evidence of immunity to rubella or varicella: MMR and/or
varicella
Tetanus/diphtheria/pertussis if lacking adult vaccination
Age
All girls and women 9 –26 yr old: HPV
All persons 18 yr and younger without immunity to hepatitis B
infection: hepatitis B
Occupational
Health care workers: hepatitis B, influenza, MMR, varicella
Public safety workers who have exposure to blood in the
workplace: hepatitis B
Students in schools of medicine, dentistry, nursing, laboratory
technology, and other allied health professions: hepatitis B
Staff of institutions for the developmentally disabled: hepatitis B
Individuals who work with HAV-infected nonhuman primates
or with HAV in a research laboratory setting: hepatitis A
Military recruits: meningococcus
Microbiologists routinely exposed to Neisseria meningitidis
isolates: meningococcus
Social history/living situation
Individuals with more than one sexual partner in the previous
6 months: hepatitis B
Household contacts and sexual partners of individuals with
chronic Hepatitis B infection: hepatitis B
Inmates of correctional facilities: hepatitis B
Clients of institutions for the developmentally disabled:
hepatitis B
Illegal-injected drug users: hepatitis B
Illegal drug users (injected and non-injected): hepatitis A
Exposure to environment where pneumococcal outbreaks
have occurred: pneumococcus
Native Alaskan/native American: pneumococcus
Alcohol abuse: pneumococcus
Tobacco smoking: pneumococcus
Residents of long-term care facilities: influenza, pneumococcus
First year college students living in dormitories: meningococcus
Travel/immigration
Individuals traveling to or working in countries that have high
or intermediate endemicity of hepatitis A: hepatitis A
International travelers who will be in countries with high or
intermediate prevalence of chronic Hepatitis B infection for
more than 6 months: hepatitis B
Travel to areas hyperendemic or epidemic for Neisseria
meningitidis: meningococcus
Pulmonary conditions
Chronic pulmonary disorders, including asthma:
pneumococcus
Cardiac conditions
Chronic cardiovascular disorders (e.g., CHF, cardiomyopathies):
influenza, pneumococcus
Renal conditions
Chronic metabolic diseases, including renal dysfunction:
influenza, pneumococcus
Nephrotic syndrome: pneumococcus
End stage renal disease including those on dialysis: hepatitis B
(continued)
 Preconception Care Y CME Review Article
TABLE 5
Continued
Endocrine conditions
Diabetes mellitus: influenza, pneumococcus
Hematologic/immunologic conditions
Prior transfusions: hepatitis A; hepatitis B
Patients with clotting factor disorders (those who receive
clotting factor concentrates): hepatitis A
Chronic illness, such as functional asplenia (e.g., sickle cell
disease) or splenectomy: pneumococcus
Immunocompromised patients (e.g., HIV infection,
hematologic or solid malignancies, chemotherapy, steroid
therapy): pneumococcus
Adults with anatomic or functional asplenia: pneumococcus,
meningococcus
Terminal complement component deficiencies: meningococcus
Infectious conditions
Individuals with a recently acquired or recent evaluation for
STD: hepatitis B
All clients in STD clinics: hepatitis B
HIV: hepatitis B, influenza, pneumococcus, consider
meningococcus
GI/hepatic conditions
Chronic liver disease: hepatitis A, hepatitis B, pneumococcus
Neurologic conditions
Cerebrospinal fluid leaks: pneumococcus
Modified from Obstet Gynecol 2006;108:1615–1622.
infections such as rubella and varicella should be
assessed for potential vaccination of nonimmune
women, thus eliminating their risk for congenital
syndromes associated with these viruses. Vaccina-
tion with live-attenuated viruses should occur at least
4 weeks before conception due to theoretical risk of
live virus affecting the fetus.
Annual influenza vaccination for women and their
partners contemplating pregnancy will reduce the
chance of maternal prenatal infection, a time during
which higher morbidity has been documented. Influ-
enza vaccination for new mothers and other close
contacts of the newborn will reduce risk of infection
for the child who is unable to receive vaccination
until 6 months of age. Through this process of
“cocooning,” the newborn is protected from the high
morbidity and mortality rates associated with influ-
enza in the first year of life (29).
Hepatitis B vaccination should be offered to all
susceptible women of reproductive age in regions
with intermediate and high rates of endemicity
(where ⱖ2% of the population is HBsAg positive).
Perinatal transmission of hepatitis B results in 90%
chance of chronic infection in the newborn, which
places the child at risk for future cirrhosis and hep-
atocellular carcinoma. In regions of low prevalence,
vaccination should be targeted to high risk groups
(Table 5).
125
Tetanus vaccination should remain up to date in
reproductive age women, particularly in regions of
the world where maternal and neonatal tetanus is
prevalent (30). This has been shown to markedly
reduce the incidence of tetanus related to parturition.
Due to increasing prevalence and the high morbidity
and mortality rates of neonatal pertussis, vaccination
(in combination with tetanus and diphtheria) is rec-
ommended for all women and their partners of re-
productive age who have not been immunized in
their adult lives (since age 11 years) (31). It is well
documented that 75% of cases of neonatal pertussis
have a family member as the index case (32). Again,
through the concept of cocooning, the incidence of
neonatal pertussis can be reduced.
Other vaccination recommendations based on med-
ical, occupational, or social risks are described in
Table 5.
Injury Prevention
The second leading cause of death in reproductive
age women is accidents. Use of seat belts and hel-
mets should be reviewed and strongly encouraged
where appropriate. Inquiry should be made regarding
occupational and recreational hazards. Possession
and use of firearms should be evaluated.
Specific Individual Issues
Chronic Diseases
The incidences of several medical disorders such
as obesity, diabetes mellitus, and hypertension are
high and on the rise in reproductive-age women.
There is literature for evidence-based recommenda-
tions on each disease or condition that can involve
the reproductive age woman and affect her reproduc-
tive health (3,8,10). Full review of each is behind the
TABLE 6
Preconception interventions for all women
Intervention Prevention of
Folic acid 400 ␮g/d* NTDs, possibly cardiac defects,
facial clefts
Vaccinations Maternal/perinatal infection† (Table 5)
Proper diet and Obesity, diabetes, hypertensive diseases,
exercise and their consequences
Screen for specific Table 7
risk factors
*Consider higher dose, especially for women taking anti-seizure
medications, other drugs which might interfere with folic acid
metabolism, those with homozygous MTHFR enzyme mutations,
or those who are obese.
†
By decreasing perinatal transmission, also decrease congen-
ital defects caused by infection.
126 Obstetrical and Gynecological Survey

scope of this review. In addition to recommendations
for all women (Table 6), we selected some common
conditions for brief preconception management re-
view (Table 7).
Diabetes is associated with an increased risk of
congenital anomalies, in particular cardiac and neural
tube defects, if poorly-controlled in the first weeks of
pregnancy. The risk of congenital anomalies is re-
lated to long-term diabetic control, reflected in the
level of glycosylated hemoglobin (HgB A1c): ⬍7%
⫽ no increased risk (2%–3% baseline); 7%–9% ⫽
15%; 9%–11% ⫽ 23%; ⬎11% ⫽ 25% (33). It has
been estimated that euglycemia (with normal HgB
A1c) during the first trimester, which can only be
achieved through attentive preconception counseling,
could prevent ⬎100,000 US pregnancy losses or
birth defects/year (2)! The benefits of preconception
diabetes care have been previously demonstrated
(34,35) even in teenagers (36). Preconception care is
also essential for counseling of the woman with

TABLE 7
Preconception interventions for women with selected specific risk factors
Risk Factor/Population Intervention
Smoking Smoking cessation
Alcohol Avoid all alcohol intake
Other drugs of abuse Avoid all drugs of abuse
Teratogenic drugs Avoid teratogenic drugs (Table 8)
Supplements and over-the- Review and counsel: avoid excess of
counter medications recommended daily allowance (RDA)
Diabetes Hemoglobin A1C ⬍7%; screening for
asymptomatic bacteriuria
Obesity Diet and exercise to achieve normal BMI;
screening for diabetes
Hypertension Avoid angiotensin-converting enzyme
inhibitors and angiotensin-receptor
blockers. If long-standing HTN, assess
for renal disease, ventricular
hypertrophy, and retinopathy
Hypothyroidism Thyroxine supplementation to maintain
normal TSH (0.5–2.0 mcu/ml)
Hyperthyroidism PTU (propylthiouracil) supplementation to
maintain FT4 in high normal range, and
TSH in low normal range
Seizure disorders Lowest dose of safest effective
anticonvulsant monotherapy; folic acid
4 mg/d
Asthma Management following National Asthma
Education and Prevention Program
(NAEPP)
Systemic lupus erythematosus ⱖ6 mo of quiescence on stable therapy
HIV Initiate or modify antiviral agents with
goals of: (1) HIV-1 RNA viral load level
⬍1000 copies/mL or below the limit of
detection of the assay (2) avoid
teratogenic agents
PKU Low-phenylalanine diet
Sexually transmitted disease Screen at risk populations (Tables 3, 4)
(e.g., chlamydia)
Social issues (e.g., abuse, etc.) Counseling; referral to appropriate agency
PTB indicates preterm birth; LBW, low birth weight; IUGR, intrauterine growth restriction; NICU, neonatal intensive care unit; BMI,
body mass index; NTD, neural tube defects; CD, cesarean delivery; HTN, hypertension; VTE, venous thromboembolism; TSH,
thyroid-stimulating hormone; FT4, free thyroxine; HIV, human immunodeficiency virus; RNA, ribonucleic acid; PKU, phenyl ketonuria.
Prevention of
PTB, LBW, etc.
Congenital anomalies, mental retardation
PTB, IUGR, neonatal withdrawal, etc. (effect
depends on drug of abuse)
Congenital anomalies
Congenital anomalies
Congenital anomalies, length of NICU admission,
perinatal mortality and long-term health
consequences in infant; miscarriage; maternal
hospitalizations, maternal renal disease
Infertility, fetal NTDs, PTB, CD, HTN-disorders,
diabetes, VTE
Congenital anomalies, HTN complications, CD,
IUGR, placental abruption, PTB, perinatal death
Infertility, maternal HTN, preeclampsia, abruption,
anemia, PTB, LBW, fetal death, possibly
neurological problems in infant
Spontaneous pregnancy loss, PTB, preeclampsia,
fetal death, FGR, maternal congestive heart failure,
and thyroid storm; neonatal Graves’ disease
Congenital anomalies
PTB, LBW, preeclampsia, perinatal mortality
HTN, preeclampsia, PTB, fetal death, IUGR, neonatal
lupus
Perinatal HIV infection
PKU-related mental retardation
Ectopic pregnancy
Physical and emotional trauma and their
consequences
 Preconception Care Y CME Review Article
conditions severe enough to make a successful preg-
nancy extremely unlikely. The diabetic woman with
either ischemic heart disease, untreated proliferative
retinopathy, creatinine clearance ⬍50 mL/min, pro-
teinuria ⬎2 gm/24 h, creatinine ⬎2 mg/dL, uncon-
trolled hypertension, or gastropathy should be told
not to get pregnant before the above conditions can
be improved, and counseled regarding adoption if the
conditions cannot be improved (37). The frequency
of fetal/infant and maternal morbidity and mortality
are reduced in diabetic women seeking consultation
in preparation for pregnancy, but unfortunately only
about a third of these women receive such consulta-
tion (38). The preconception consultation affords the
opportunity to screen for vascular consequences of
the diabetes, with ophthalmologic, EKG, and renal
evaluation via a 24-hour urine collection for total
protein and creatinine clearance, and determine an-
cillary pregnancy risks. A thyroid-stimulating hor-
mone should be checked, as 40% of young women
with type 1 diabetes have hypothyroidism. Prolifer-
ative retinopathy should be treated with laser before
pregnancy. Diabetes evaluation should emphasize
the importance of tight glycemic control, with nor-
malization of the HgB A1C to at least ⬍7%. To
achieve euglycemia, diet, glucose monitoring, and
exercise are always used and stressed. If euglycemia
is not achieved with these means, oral hypoglycemic
agents or insulin are utilized, and their regimens
should be refined preconceptionally. Of the oral hy-
poglycemic agents, glyburide and glucophage can be
used, and probably continued during pregnancy. The
original safety data available for glyburide showed
that it did not cross the placenta in appreciable
amounts (39), but recent data have shown a 70% level
in umbilical blood compared to maternal blood (40).
The other oral hypoglycemic agents should not be
used for preconception glycemic control, as there is
not sufficient evidence for their safety and efficacy in
pregnancy. A common regimen currently used by
diabetologists is long-acting (e.g., glargine) and
short-acting (e.g., lispro insulin). There is growing
evidence that this is a safe and effective regimen in
pregnancy, too. Women compliant with insulin
pumps should continue this regimen.
Hypertension is associated with several maternal
(worsening hypertension; superimposed preeclampsia;
severe preeclampsia; eclampsia; hemolysis, elevated
liver function texts, low platelets (HELLP) syndrome;
cesarean delivery) and fetal (growth restriction;
oligohydramnios; placental abruption; preterm birth;
perinatal death) risks in pregnancy. Serum creatinine,
24 hour urine for total protein and creatinine clearance,
127
electrocardiogram, and ophthalmological exam, and
ophthalmological exam are suggested, especially in
women with long-standing, high-risk, or severe hyper-
tension. It is important to identify cardiovascular risk
factors, any reversible cause of hypertension, and assess
for target organ damage or cardiovascular disease. If
hypertension is newly diagnosed and has not been eval-
uated previously, a medical consult may be indicated to
assess for any of these factors. Secondary hypertension,
target organ damage (left ventricular dysfunction, reti-
nopathy, dyslipidemia, microvascular disease, prior
stroke), maternal age ⬎40, previous pregnancy loss,
systolic blood pressure ⱖ180, or diastolic blood pres-
sure ⱖ110 mm Hg are associated with higher risks in
pregnancy. Abnormalities should be addressed and
managed appropriately. If, for example, serum creati-
nine is ⬎1.4 mg/dL, the woman should be aware of
increased risks in pregnancy (pregnancy loss, reduced
birth weight, preterm birth, and accelerated deteriora-
tion of maternal renal disease). Even mild renal disease
(creatinine, 1.1–1.4 mg/dL) with uncontrolled hyperten-
sion is associated with 10-fold higher risk of fetal loss.
Preconception prevention can be enormously effective.
Exercise for 30 minutes 3 times per week in all women
with hypertension, and weight reduction if overweight
are recommended. Restriction of sodium intake to the
same ⬍2.4 gm sodium daily intake recommended for
essential hypertension is beneficial in nonpregnant
adults. If antihypertensive medical therapy is necessary,
angiotensin-converting enzyme (ACE) inhibitors and
angiotensin-II (AII) receptor antagonists should be dis-
continued as they are associated with birth defects, fetal
growth restriction, oligohydramnios, neonatal renal fail-
ure, and neonatal death in pregnancy. Other antihyper-
tensive agents should be used at the lowest effective
dose, and are probably safe if started preconceptionally
and continued in pregnancy.
Regarding seizures, conception should be deferred
until they are well controlled on minimum dose of
medication. Monotherapy is preferable. Recently,
lamotrigine has been reported to be both first-line
therapy for nonpregnant adults for partial seizures,
(41,42) and associated with a low incidence of major
malformations (43). The best choice is the antiepi-
leptic drug (AED) that best controls the seizures. The
AEDs are usually Food and Drug Administration
category C (human risk unknown, but none proven
yet) except for the following AEDs, which are
known potential teratogens: carbamazepine, primi-
done, phenytoin, and valproate (Table 8). These 4
AEDs should therefore be avoided if possible, by
using a different therapy beginning in the precon-
ception period. Women who have been seizure-
128 Obstetrical and Gynecological Survey

TABLE 8 preconception care, and can save and ameliorate sig-

Teratogens nificantly the health of a future offspring. Great re-
Prescribed drugs sources exist on the web for up-to-date teratologic
Androgens and testosterone derivatives (e.g., danazol) information (47–49).
Angiotensin-converting enzyme (ACE) inhibitors (e.g.,
enalapril, captopril) and angiotensin II receptor blockers Substance Abuse/Environmental Hazards/Toxins
Coumadin derivatives (e.g., warfarin)
Carbamazepine Tobacco smoking during pregnancy is associated
Diethylstilbestrol with increased risks of several complications. The
Folic acid antagonists (methotrexate and aminopterin) benefits of smoking cessation are tremendous: pre-
HMG-CoA reductase inhibitors (statins)
Lithium
vention of 10% of perinatal deaths, 35% of low
Phenytoin weight births, and 15% of preterm deliveries (50).
Primidone Smoking even only 1 to 5 cigarettes per day is
Streptomycin and kanamycin associated with a 55% higher incidence of low birth
Tetracycline weight compared to nonsmokers. Reproductive-age
Thalidomide and leflunomide
Trimethadione and paramethadione
women should be informed of other smoking-related
Valproic acid diseases, such as ischemic heart disease, lung and
Vitamin A above RDA, and its derivatives (e.g., isotretinoin, other cancers, other lung diseases and pneumonia,
etretinate, and retinoids) stroke, and congestive heart failure. Major risk
Chemicals groups for smoking are women ⬍25 years old with
Lead
Mercury
less than a high-school education. Smoking makes a
Drugs of abuse major contribution to disparities in mortality (51).
Alcohol Smoking cessation programs are based mostly on
Cocaine oral and written advice at each prenatal visit regard-
Infections ing the risk of smoking for mother and baby, and
Cytomegalovirus
Rubella
plan to quit. These programs are associated with a
Syphilis 6% increase in smoking cessation, and decreases in
Toxoplasmosis incidences of low birth weight (by 19%) and preterm
Varicella birth (by 16%) (52). Support and reward techniques
Radiation to help quit smoking are one of the best form of
Modified from Lancet 2007;369:970–971 and Neurology 2008; evidence-based medicine, supported by over 20 high
71:706–707. quality randomized trials. The “5 A’s” for screening
and interventions to prevent smoking in pregnancy
free for ⱖ2 years with a normal EEG may be are Ask, Advise, Assess, Assist, and Arrange (53).
eligible to stop anticonvulsant therapy after con- Counseling with behavioral and educational inter-
sulting with a neurologist (44). ventions is associated with highest cessation rates.
Pregnancy is a unique opportunity for medical inter-
Medications/Teratogens
vention with frequent visits and may be the only time
Detailed discussion regarding prescribed and over smoking women seek medical attention. Most phar-
the counter medications needs to occur at the precon- macotherapies are also effective preconceptionally,
ception visit. The indication, safety, effectiveness, but contraindicated or with uncertain safety and
and necessity of each drug needs to be reviewed. efficacy during pregnancy. Nicotine replacement
Many women and their doctors often stop efficacious therapies (patch, gum, and bupropion) are safe and
and necessary medications as soon as the woman effective in reproductive-age women, but there is
finds out she is pregnant, compromising the health of insufficient evidence for recommending them in
both the woman and her baby. The majority of pre- pregnant smokers. Nicotine replacement therapy is
scribed medications are safe in pregnancy, even in associated with known adverse fetal effects and nic-
the first trimester, as they have not been shown to be otine is detected in breast milk. Possibly the best
teratogens. Only a few drugs, chemicals, infections, prevention of the adverse effect of smoking to preg-
or radiation are proven teratogens (Table 8) (45,46). nancy is achieved by avoidance of sales of tobacco to
These should be avoided, except in rare circum- young people, prohibition of smoking in public
stances (e.g., the woman with mechanical cardiac places, increase in tobacco taxation, workplace
valves who accepts the teratogenic risk of warfarin). smoking cessation programs, and banning of tobacco
This medication counseling is often a crucial part of sponsorship of sporting and cultural events.
 Preconception Care Y CME Review Article
Numerous recreational drug exposures have ad-
verse pregnancy effects. This list is extensive and
includes but is not limited to common recreational
drugs such as alcohol, cannabinoids, cocaine, heroin,
and methamphetamines. Working to ensure that
women with substance abuse issues engage in safe
sex practices and family planning is a constant chal-
lenge, and these women are disproportionately over-
represented among women with unplanned pregnancies.
Current Evidence, Future Research, and Needs
for Preconception Care
Evidence supports specific preconception interven-
tions in all women (Table 6), and in women with
specific risk factors (Table 7). There is less evidence
to support comprehensive preconception screening,
counseling, and intervention, and more research is
needed in this area. A standardized form improves
the completeness of preconception screening, which
necessitates time and commitment (54). The form
should be given (or mailed) and filled out by all
women of reproductive age before any medical visit
(Table 1). This standardized preconception form
must be integrated into the permanent record of all
reproductive-age women. In a nonrandomized study,
preconception care decreased the number of unin-
tended pregnancies (55). In a randomized trial,
women assigned to be screened with a preconception
risk survey were found to have an average of 9 risks
factors, supporting the facts that even low risk
women may benefit from preconception screening
(56). General-practitioner initiated preconception
counseling not only can decrease adverse pregnancy
outcomes, but also reduces anxiety in reproductive
age women (57).
Despite its great effectiveness, not all health care
plans cover preconception care. One clear necessity
is a political will and need for funding and insurance
coverage for preconception care. Further research is
needed to determine the best content of preconcep-
tion care and the most effective ways to implement
its use (56,58).
CONCLUSION
The time that people should start caring for a preg-
nancy is not after, but before it happens. Evidence-
based medicine and science support preconception
care as effective in improving maternal and infant
health. A preconception visit (or often more than
one) should be standard primary care, as stated by the
Centers for Disease Control and Prevention in 2006
(2). It should be as routine, if not more so, as prenatal
129
care, and its screening and interventions as routine as
those for prenatal care.
We believe physicians of all specialties should be
aware of these evidence-based recommendations
(Tables 1–8). Organizations representing family and
internal medicine, obstetrics and gynecology, nurse
midwifery, nursing, public health, diabetes, neurol-
ogy, cardiology, and many other associations have
supported recommendations in preconception care.
Unfortunately, practitioners seldom implement them,
(59) even if this is an opportunity to optimize the
health of the woman independently of whether she
becomes pregnant (5). Only 1 out of 6 ob-gyns or
family physicians provide preconception care to the
majority of women for whom they provide prenatal
care (60). Preconception care is based on the specific
risks identified, and individualized care. No single
pill ensures preconception health and a successful
pregnancy. Once a preconception plan is in place,
further preconception care may be necessary every
time a new risk (disease, medication, etc.) arises.
Preconception care is a process to care, not just a
single office visit. Pregnancy is a temporary condi-
tion, not a disease. As there are 2 patients in one,
special precautions are necessary. Maternal physiol-
ogy is different than nonpregnant adult physiology.
An entire field, maternal-fetal medicine, is dedicated
to the care of pregnancies with maternal or fetal
problems, and these specialists are particularly adept at
directing best practices for preconception counseling.
As the preconception woman can have numerous
different medical problems affecting different spe-
cialties, preconception care needs to be multidisci-
plinary care, and occur in close collaborations
between the different fields involved. Preconception
care only occurs if all practitioners, including pri-
mary and specialty care, either directly implement or
appropriately refer for implementation of effective
preconception screening and intervention. The worse
scenario is the belief that a positive pregnancy test is
a good reason to stop “all medicines” and to stop
treating diseases. Prevent panic: get women ready for
a healthy pregnancy before contraception is stopped.
Moreover, reproductive-age women should be
aware of these evidence-based recommendations
(Tables 6, 7), through their doctors but also through
public awareness campaigns. Several on line re-
sources are available (61–64). Women and their part-
ners should take more responsibility for their care and
the future health of their offspring, and implement the
health and lifestyle changes recommended. Preconcep-
tion counseling offers the opportunity for improved
cooperation with women, increased planned pregnan-
130 Obstetrical and Gynecological Survey
cies, and decreased terminations of pregnancy. It also
leads to cost savings, due to fewer hospitalizations
for the mother, fewer anomalies for the fetus, etc. A
sick child, as a consequence of missed opportunities
for prevention in preconception care, is a burden not
only for him/herself, and his/her family, but for the
whole community.
While some of the interventions could theoretically
be started as soon as a pregnancy test turns positive,
this is unrealistic. Moreover, some of the preventive
measures take time, often months, such as quitting
smoking, losing weight, folic acid supplementation,
infertility management, and stabilization of medical
conditions with effective and safe medications.
For the future, preconception care must become
routine for each visit of a reproductive-age woman to
a health-care provider. Programs for preconception
health and task forces should be in place. Physician
as well as consumer awareness should be increased,
and incentivized by physician pay for performance
and consumer insurance discounts for obtaining pre-
conception care. Every woman should be aware and
afforded the benefits of this opportunity.
Research should continue to better define the evidence-
based content of preconception care, appropriate in-
terventions, and their cost-effectiveness. We need to
understand how to best think globally, but act locally,
at the individual level (65). The percent of women
obtaining preconception counseling should be
tracked, with the aim to bring it as close as possible
to 100%, as we expect for prenatal care. Selected
preconception health indicators (folic acid, smok-
ing, obesity, diabetes, vaccinations, etc) should be
monitored to track successful improvements in
health.
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