This chapter should be cited as follows: This chapter was last updated:
Moose, M, Cefalo, R, Glob. libr. women's med.,
(ISSN: 1756-2228) 2008; DOI 10.3843/GLOWM.10112
October 2008

Preconceptional counseling and prenatal care

Preconception Counseling

Merry-K. Moose, MD
Professor of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC, USA
Robert C. Cefalo, MD, PhD
Professor Emeritus of Obstetrics and Gynecology, University of North Carolina School of Medicine, Director of the Medical Residency and Fellowship Programs at UNC Hospitals, Chapel Hill, NC, USA

INTRODUCTION

Obstetrician/gynecologists are often called on to provide diagnosis and treatment of disease, but they are routinely also called on to provide primary and preventive care. For many women, the only healthcare provider encountered in an entire year is their obstetrician/gynecologist. Responsibilities for preventive care include prevention counseling for the woman herself as well as education and counseling to promote the health of any pregnancies she may someday conceive. This latter emphasis has come to be known, over the last 20 years, as preconceptional counseling. Preconceptional counseling emanates from data indicating that there are unfavorable maternal and fetal outcomes associated with specific pre-existing maternal conditions that could be avoided through prepregnancy interventions.1 The benefits of deliberately preparing for pregnancy relate to the important and critical period of organogenesis, which occurs between days 17 and 56 postfertilization; the traditional early prenatal visit is too late to affect reproductive outcomes associated, for instance, with abnormal organogenesis.

Preconception health promotion and healthcare are not new concepts; they have been gaining momentum in Europe and the United States for nearly thirty years.2  In 1985, the Institute of Medicine (IOM) called for reconsideration of the usual paradigm for preventive services for maternal and neonatal health.3 Subsequently, Healthy People 2000, the health promotion and disease prevention objectives for the United States, put forth a target to increase to at least 60% the proportion of primary care providers who provide age-appropriate preconception care and counseling by the year 2000.4 In 2005, the U.S. Centers for Disease Control and Prevention (CDC) convened a Select Panel on Preconception Care.5 The Panel brought together representatives from 35 national organizations and 22 CDC Programs to develop a consensus agenda to reframe the perinatal prevention paradigm.  The Panel determined that preconception care is a critical component of healthcare for women of reproductive potential and defined it as "a set of interventions that aim to identify and modify biomedical, behavioral and social risks to a woman's health or pregnancy outcome through prevention and management". 5 Existing clinical guidelines for 14 conditions formed the backbone of the recommendations. 5.  In order to move the agenda forward, the Select Panel developed implementation recommendations in three areas:  clinical practice, consumer roles and public health practice.  The clinical practice guidelines will be published as a supplement to the American Journal of Obstetrics and Gynecology in early 2009.

Paradigm shifts do not often proceed without rethinking, re-examination and reformulation. As preconceptional health becomes more accepted as a routine health promotion emphasis, many questions are raised6:

  • Is preconceptional care best targeted to the general population or to specific subsets?
  • Should it always be offered as a routine component of well-woman care or delegated to a special visit?
  • Do all potentially fertile women want preconception services?
  • Is preconceptional care cost-effective?
  • Must preconceptional risk assessment and related education be provided in a clinical setting?
  • How do multiple providers avoid competing or conflicting recommendations?
  • What strategies best encourage busy providers to incorporate a prevention emphasis into routine encounters?

For most women, the routine well-woman visit presents the ideal time to provide preconceptional counseling. Well-woman visits, which are also called routine assessments, are defined by the American College of Obstetricians and Gynecologists (ACOG) as including screening, evaluation, and counseling based on age and risk factors.7 At this visit, risks to the woman’s health should be identified; these risks can then be evaluated relative to the woman’s immediate and long-term healthcare expectancies, as well as those of any offspring that might be conceived in the future. Little that could be recommended in routine preconceptional counseling would not benefit the average woman’s general health status, irrespective of eventual conceptions.8

For instance, whether the woman plans to become pregnant or not, her smoking habits should be determined at every visit and clear recommendations and strategies for cessation, if needed, offered. To do less is to give poor care relative to the woman’s immediate needs; however, in providing this emphasis in each routine visit, not only is the woman’s health addressed but also her preconceptional wellness.8

Similarly, addressing a woman’s weight status and dietary intake at her routine wellness visit has the potential to affect not only her immediate and long-term health but also the health of future pregnancies, should she conceive. Asking women at each visit about their desires for future conceptions not only offers information on which to base contraceptive counseling but also provides a natural, important, and often overlooked opportunity to educate about the benefits of pregnancies that are intended.8

By addressing the reproductive intentions and contraceptive practices and needs of every woman who presents for care, providers may be able to decrease the likelihood of a woman experiencing an unintended pregnancy and support her in achieving her reproductive health plan.  By addressing the health promotion needs of every woman who presents for care and eliciting and addressing her health profile for reproductive risks, irrespective of her desires for pregnancy, it is likely that more women will enter pregnancy with high levels of preconception wellness and that healthier women and healthier pregnancies and infants will result.9 

A recent study suggests that providers are not taking advantage of preconceptional health promotion opportunities afforded by routine gynecology visits.10 In a review of the medical records of 100 women of an inner-city gynecology service, assessments important to medical care, in general, as well as to preconceptional health promotion, in particular, were rarely present. Whereas 71% of the records noted that family planning methods had been assessed and 72% documented that toxic habits had been investigated, other areas traditionally considered components of a routine assessment were not generally present. Less than 30% of the records included documentation of a thorough medical history, over-the-counter drug exposures, domestic violence, nutritional status, and dietary supplementation. Just 30% included evidence that prescription drug use had been explored. The researchers hypothesized that because preconceptional counseling as a routine component of care for all reproductive age women is a relatively recent emphasis for care, it has yet to become routine. The results of the study pointed out, however, that issues important to well-woman care, irrespective of the likelihood of future conceptions, were being overlooked.8 Following an educational intervention that included information aimed at heightened awareness of opportunities to integrate preconceptional health information into routine encounters, statistically significant improvements were recorded for all the health assessments. These improvements reflect better care for women in general, not only women likely to conceive before their next encounter.

The importance of preconceptional health promotion activities should be included in the residency and continuing medical education of all primary care physicians, including obstetricians and gynecologists. In 1995, Conway and associates11 studied the type of preconceptional counseling likely to be offered to women of reproductive age by 140 internal medicine and 42 family practice residents at Cook County Hospital. Residents were asked to answer an anonymous, self-administered questionnaire. During a 2-week period, 115 of 140 (82%) internal medicine residents and 28 of 42 (67%) family practice residents completed the questionnaire. The knowledge score consisted of a total of 46 items in a true-or-false format. Hypothetical patients and recommended management decisions were presented relating to rubella immunization, potential for congenital anomalies in diabetic patients, and management of chronic hypertension. More than 40% of the residents failed to indicate that they would provide a healthy woman information about rubella immunization, family planning, or counseling on sexually transmitted disease and safer sex. When counseling a diabetic woman seeking pregnancy, 74% of the residents would not have discussed congenital anomalies with her, and 45% would not have considered discontinuing oral hypoglycemics if she became pregnant. Fifty-eight percent would have neglected to review or change hypertensive medications in a newly diagnosed pregnant woman. No studies have been located that indicate that progress has been made in the educational impact of our residency programs.

IDENTIFICATION OF REPRODUCTIVE RISKS

Each well-woman examination for women of reproductive potential should include assessment of the woman’s health, desires regarding future conception, and anticipation of risks should pregnancy occur for both the woman and the conceptus. The preconceptional assessment should not be reserved for women who indicate they hope to become pregnant in the immediate future. To limit assessments to this population is likely to result in missed opportunities for prevention education because nearly half (49.2%) of all pregnancies in the United States occur to women who were not intending to become pregnant at the time they did.12 These pregnancies, which are termed unintended, occur in all subgroups of sexually active women; rates vary by age and socioeconomic and marital status.12 The highest rates are for women younger than 20 years and women older than 40 years, but the largest number of unintended pregnancies occur in women aged 20–24 years. Among married women, 31% of pregnancies are self-reported as unintended.

A well-woman examination for someone who might become pregnant, in other words, a preconceptional visit, involves risk identification, provision of education individualized to specific needs, and initiation of desired interventions. To identify potential reproductive risks, a preconceptional assessment should include routine and systematic inquiries into each woman’s medical, reproductive, and family histories; nutritional habits; drug exposures; and psychosocial profile.13 As noted previously, some routine well-woman assessments, even for women who could become pregnant in the future, do not cover all the important areas. To aid the physician in undertaking a thorough baseline assessment, Table 1 provides appropriate topics for investigation in each area of the preconceptional assessment and Table 2 lists laboratory testing that may be indicated for a woman who could become pregnant.

 

Table 1. A preconceptional health assessment tool

  Medical History
  Is the patient under current or former treatment for:

  Diabetes mellitus?
  Thyroid disorders?
  Hyperphenylalaninemia?
  Asthma?
  Heart disease?
  Chronic hypertension?
  Deep venous thrombosis?
  Kidney disease?
  Systemic lupus erythematosus?
  Epilepsy?
  Hemoglobinopathies?
  Cancer?


  Does the patient have occupational exposure to the blood or bodily secretions of others?
  Does the patient engage in high-risk behaviors for exposure to the human immunodeficiency virus?
  Does the patient handle feline litter boxes or eat raw or very rare meat?
  Does the patient routinely or occasionally take any prescribed medications?
  Does the patient routinely or occasionally take any over-the-counter medications?
  

Reproductive History
  Has the patient had:

  Uterine or cervical abnormalities?
  Two or more pregnancies ending in first trimester miscarriage without an intervening successful gestation?
  One or more fetal deaths?
  One or more preterm deliveries?
  One or more small-for-gestational-age infants?
  One or more infants requiring care in a neonatal intensive care unit?
  One or more infants with a birth defect?


  Nutrition
  Does the patient:

  Practice vegetarianism?
  Eat a special diet?
  Have a history of bulimia or anorexia?
  Use vitamin supplements in excess of the RDA
  Have a history of pica?
  Weight < 85% or > 135% of the ideal for height?
  Consume adequate folic acid?


  Family History
  Does the patient, her partner, any of their offspring, or any members of their families have:

  Hemophilia?
  Thalassemia?
  Tay-Sachs trait or disease?
  Sickle cell disease or trait?
  Phenylketonuria?
  Cystic fibrosis?
  Birth defects?
  Mental retardation?


  Social History
  Does the patient

  Drink beer, wine, or hard liquor?
  Smoke cigarettes or use other tobacco products?
  Use marijuana, cocaine, or any similar drugs?
  Use lead or chemicals at home or at work?
  Participate in activities that could result in overheating (e.g. saunas, hot tubs, demanding exercise in hot, humid conditions)?
  Have evidence of current or former physical, sexual, or psychological abuse?
  Have a plan for spacing and timing her pregnancies?
  Have maternity benefits in her insurance program that cover her and a future neonate?
  Know her employer’s policies around pregnancy and birth?



RDA, recommended dietary allowance.
Modified from Cefalo RC, Moos MK: Preconceptional Care: A Practical Guide. St. Louis, CV Mosby, 1995

 

 

Table 2. Laboratory tests that may be ordered preconceptionally

  Hematocrit
  Rubella serology, immunization if indicated
  Varicella titer, immunization if indicated
  Syphilis serology
  Screenings

  Toxoplasmosis
  Hepatitis B surface antigen
  Chlamydia
  Gonorrhea
  Tuberculosis
  Human immunodeficiency virus
  Tay-Sachs disease
  Cystic fibrosis
  Sickle cell
  Pap smear


 

Through preconceptional healthcare, the woman or couple should come to understand any specific reproductive risks they have and steps they can take around the time conception is desired to increase the likelihood of a healthy pregnancy and child. With this information, they can accept existing risks, choose to reduce the risks, or opt to avoid childbearing.1 These evaluations are not all-inclusive and need to be individualized according to the full assessment of the patient and her family. The remainder of the chapter highlights selected risks and prevention opportunities that may be uncovered in the assessment process.

Nutrition

Nutrition and its importance to reproductive outcomes should be emphasized in all well-woman and preconception counseling visits. Appropriateness of weight for height, special childhood diets, and nutrition patterns (e.g. vegetarianism, fasting, pica, bulimia, vitamin supplementation) deserve thorough investigation. Adolescent and adult women, like most Americans, are prone to poor food choices and eating habits—skipping meals, eating high-fat foods, consuming few fruits and vegetables, and engaging in fad or chronic “dieting.” The assumption that overweight women are getting adequate nutrients (only in excess) is faulty. Indeed, malnutrition can take the form of overweight (body mass index [BMI > 27) or underweight (BMI < 20), and both present risks to the women beginwoman’s health, to her health in pregnancy, and to the health of her fetus. Therefore, assessment and counseling regarding weight status should be a feature of all well-woman care. Having a professional relationship with a nutritionist or dietician in the community is beneficial to facilitate referrals for women who desire to address their weight status and wish specific guidance. Whereas obesity has long been associated with prenatal and intrapartum complications of pregnancy, more recent evidence suggests that it may also be an independent risk factor for the occurrence of neural tube defects (NTDs).14 Prevention strategies against the development of NTDs in the general population, as discussed later, do not seem to have the same effectiveness in the obese population as for other women. The one strategy that may offer protection for this segment of childbearing women is preconceptional guidance and support for weight reduction.

Evidence began to accumulate more than 20 years ago that maternal folic acid levels affect normal embryogenesis.15, 16, 17, 18, 19, 20, 21, 22, 23 The research suggests that women who take a vitamin supplement containing folic acid and eat foods fortified with folic acid have fewer pregnancies complicated by oral clefts, congenital heart defects, limb reduction anomalies, and urinary defects. The strongest body of research, which started with observational studies and culminated in randomized controlled trials, has resulted in consensus that neural tube development is benefited by folic acid. Each year in the United States more than 4000 pregnancies are complicated by NTDs, and between 2500 and 3000 infants are born with the condition.24

Because the research indicated that 50–70% of NTDs could be prevented by adequate periconceptional folic acid intake, the US Public Health Service (USPHS) released a landmark recommendation in 1992 that read: “All women of childbearing age in the United States who are capable of becoming pregnant should consume 0.4 mg of folic acid per day for the purpose of reducing their risk of having a pregnancy affected with spina bifida or other neural tube defects.”25 To help women obtain adequate folic acid, the U.S. Food and Drug Administration (FDA) approved a population-based strategy to fortify grain food sources with folic acid effective January 1998. The fortification levels were set at a relatively low level, however, making it difficult to achieve the recommended intake. In 1998, the IOM reaffirmed the USPHS recommendation and added that women of childbearing years should take 0.4 mg of synthetic folic acid daily, obtained from fortified foods and/or supplements, as well as consume a balanced, healthy diet of folate-rich foods.26

Ten years have passed since the USPHS recommendation and surprisingly little impact has been made on knowledge and practices around folic acid by healthcare professionals and by women of childbearing age. Starting in 1995, national telephone surveys were undertaken by the Gallup Organization for the March of Dimes to assess knowledge of women ages 18–45 years about folic acid. Baseline data revealed that 25% of sampled nonpregnant women used a daily vitamin containing folic acid27; by 2001, despite much effort to encourage routine use among nonpregnant women, the number had increased to only 32%.28 The survey also investigated where women received their information about folic acid. Whereas it is known that women look to their healthcare providers for information, the surveys found providers to be a faint voice in the effort to improve the knowledge and practice of women regarding folic acid consumption. In 1995, 13% of the survey respondents identified their healthcare provider as their source of information about folic acid; in 2001, the figure had increased to only 22%. Among the women who did not take a daily supplement, 20% said they would be more likely to adopt this behavior if it was recommended by their clinician. It is rare to have such a simple prevention strategy available—its full impact can be realized only when the recommendation for supplementation becomes the routine in every well-woman encounter. Newer evidence suggests that folic acid supplementation may have health benefits beyond normal organogenesis. Women who consume at least 0.4 mg of folic acid each day may prove to have less heart disease29; in some subgroups, folic acid may protect against breast and colon cancer 29, 30, 31, 32; and there is promising animal research suggesting protection against neurodegenerative disorders.33, 34, 35

Occasionally, physicians indicate a reluctance to recommend folic acid supplementation because of fears of masking pernicious anemia. The prevalence of pernicious anemia is approximately 1 per 1000 persons, with the rate increasing to 1% of people over the age of 65 years. The masking of pernicious anemia is reported to be unlikely in the presence of normal dietary intake and/or supplementation of 1.0 mg/day or less.19 Supplementation in keeping with the USPHS recommendations for the prevention of the occurrence of NTDs should, therefore, not be cause for concern.19 There is, however, a separate recommendation for the prevention of NTDs in the offspring of women identified as high risk for this pregnancy outcome. This group includes women who have first-degree relatives with spina bifida, who have the condition themselves, or who have had a previous pregnancy affected by an NTD. The Centers for Disease Control and Prevention recommend that this group of women take supplementation with 4.0 mg folic acid beginning 1 month before desired conception and continuing through the first 3 months of pregnancy.36 It is a reasonable precaution to assess vitamin B12 status before recommending this megadose of folic acid supplementation.

Low maternal serum levels of zinc have been reported to be associated with a higher prevalence of offspring with congenital malformations.37 A normal fetal growth and an increased prevalence of NTDs have been linked to altered zinc concentrations in maternal blood or tissue; like folic acid and iron, zinc must be supplied daily by diet. Zinc is excreted through the kidneys and sweat glands, so patients who exercise strenuously may be zinc-deficient. Information concerning dietary zinc intake from animal protein, fish, shellfish, and eggs should be an important part of nutritional counseling. Because one of the main sources of zinc is animal protein food, patients who are vegetarians are at increased likelihood to be deficient. Recommending a multivitamin with 100% of the recommended dietary allowance (RDA) for both folic acid and zinc would address the need for both of these nutrients as well as others that may be deficient in the diets of vegetarians and non-vegetarians, alike.

In pregnancy, the RDA for vitamin A is 4000 IU; most prenatal vitamins contain 8000 IU or less. Offspring of women who took 25,000–150,000 IU of vitamin A (retinol or retinyl ester) daily, which is readily available in over-the-counter preparations, have an increased incidence of fetal growth restriction and urinary tract and central nervous system abnormalities.38 To avoid overdoses and potentially toxic elements, all over-the-counter preparations should be evaluated as to content.

MEDICAL HISTORY

Diabetes

Diabetes presents one of the most compelling arguments supporting preconceptional care. It also illustrates the breadth of issues that should be considered when offering prepregnancy counseling to women with chronic diseases, ranging from the likely effects of the disease on the pregnancy to the likely effects of the pregnancy on the disease.

The negative effects of diabetes on pregnancy include an increased incidence of congenital malformations, preeclampsia, macrosomia, intrauterine growth restriction, and intrauterine fetal death. These complications result in an increased neonatal morbidity and mortality related to prematurity, congenital malformations, and birth trauma. Intensive fetal monitoring and careful control of diabetes both before and during pregnancy have improved the outcome of a diabetic pregnancy, even in patients who have nephropathy, retinopathy, or other vascular complications.39 Blood glucose control in insulin-dependent diabetes mellitus (IDDM) patients treated before conception markedly decreases the incidence of major congenital malformations compared with patients who achieve blood glucose control after entering prenatal care.40, 41

The natural course of diabetic nephropathy is not accelerated by pregnancy, but pregnant women with diabetic nephropathy do have a high rate of fetal morbidity, largely owing to prematurity.42 Kimmerle and colleagues43 followed 29 patients from 1982 to 1992 with diabetic nephropathy, defined as proteinuria greater than 400 mg/day, creatinine clearance less than 80 mL/min, and hypertension in the first trimester. There were 36 pregnancies of 29 mothers; 31% of the fetuses had to be delivered before 34 weeks, and 25% of the newborns had respiratory distress syndrome. These results were in contrast to the near absence of these complications in 110 pregnancies of 91 IDDM patients without nephropathy in the same center and during the same period of time. End-stage renal disease requiring dialysis developed in 8 patients within 3 years postpartum, 4 of whom died during the study. Prepregnancy counseling in patients with diabetic nephropathy and severely impaired renal function should include a discussion of the potential for serious morbidity in the mother while the children are still young.

A prospective cohort study of 155 diabetic women followed from the periconceptional period to 1 month postpartum demonstrated that those patients with diabetic retinopathy were nearly three times more likely to have progression of their retinopathy if their glycosylated hemoglobin A1c (HbAlc) was 6 standard deviations above normal than women with an HbAlc within 2 standard deviations.44 Patients with a normal HbAlc and tight glycemic control with no retinopathy or only microaneurysms at conception had no new onset of retinopathy and a low risk of progression.

Patients diagnosed with IDDM before pregnancy should achieve normal plasma glucose levels with a fasting plasma level between 100 and 110 mg/dL and a 2-hour postprandial blood glucose value between 130 and 140 mg/dL with an HbA1c value in the normal range.45 To provide this important prevention opportunity, preconception care for women with diabetes, including both insulin-dependent and non-insulin-dependent disease, should be an essential component of the healthcare system, whether through dedicated preconception clinics or as an integral part of the continuum of care of the diabetic patient.

To assess the knowledge and attitudes of women with IDDM with regard to contraception, prepregnancy planning, and genetic risk, Gibb46 interviewed 124 patients with known IDDM. Eighty-five subjects were using some form of contraception. Slightly less than 50% had any knowledge about the genetic risk of passing IDDM on to an offspring. One hundred twenty (97%) said that it was “extremely important” to achieve good diabetes control before pregnancy, and 4 (3%) said it was moderately important. Fifty-two (42%) of the women were able to give a specific reason for optimal glucose control before and during pregnancy. Seventy-four patients (60%) said they would like to know more about the importance of blood glucose control and management of diabetes before and during pregnancy.

To define the social, demographic, and medical characteristics that distinguish women with established IDDM who seek preconception care from those who do not, Janz and coworkers47 reported a multicenter, case-controlled study of IDDM patients making their first preconception visit (n = 57) and compared them with pregnant IDDM patients (n = 97) who did not obtain preconception care. The patients who sought prepregnancy care were more likely to be married, living with their partners, and employed, had higher levels of education, and had an annual income greater than $20,000. They were also more likely to have discussed preconception care with their routine healthcare providers (98% versus 51%) and to have been encouraged by their providers to seek preconception care (77% versus 43%). In the prenatal group, only 24% of the pregnancies were planned. The authors emphasized that healthcare providers must strongly consider every visit with a diabetic woman of childbearing age as a preconception visit; if the patient does not plan pregnancy, contraception must be explicitly discussed. The previously discussed study was performed at three large university-affiliated teaching hospitals and two large private community hospitals. All hospitals encouraged prepregnancy counseling by means of pamphlets, posters, public service announcements, and patient education programs. Even with this organized effort, only one-third of women received such care, so it can be assumed that this fraction is higher than in institutions that do not have organized preconception care programs.

A concerning study of diabetic women entering prenatal care found that—despite the fact that the majority were under the care of a physician for their diabetes, had their blood sugars monitored at least three times a day, and stated that they had been advised to plan for conception, if that was their desire—61% presented for prenatal care with suboptimal control of their diabetes.48 This was especially true of women who had not received specific advice about target glucose levels. An interesting variable, the providers’ attitudes, was investigated in a study of 85 nonpregnant women with IDDM.49 A predictor of the women’s subsequent pregnancies being planned was whether they perceived their clinician as encouraging about the likelihood of having a healthy pregnancy outcome. When women were advised of the risky nature of pregnancy or advised to avoid pregnancy, the subsequent pregnancy was more likely to be reported as unplanned and to have laboratory indicators of poor control and entry to prenatal care.

Phenylketonuria

Infants who do not have phenylketonuria (PKU) but are born to women with classic PKU or atypical hyperphenylalaninemia with blood phenylalanine levels greater than 20 mg/dL have a high incidence of microcephaly, mental retardation, congenital heart disease, and fetal growth restriction.50, 51, 52 An excessive blood level of phenylalanine is destructive to the fetal brain; to achieve a protective effect for the fetus, preconceptional reduction of the maternal blood level of phenylalanine to the range of 4–10 mg/dL, with maintenance throughout pregnancy, is essential.51

Epilepsy

The offspring of epileptic women have an increased risk of severe congenital malformations greater than the general background prevalence of 2–3%. Some anticonvulsants are known to have serious teratogenic potential; the offspring of patients on valproic acid, for instance, have an 11 % chance of NTDs and craniofacial abnormalities. 53 Diphenylhydantoin may result in fetal hydantoin syndrome, manifested by fetal growth restriction, craniofacial anomalies, hypoplastic nails, microcephaly, and occasionally, borderline-to-mild mental deficiency (up to 10% of fetuses).54 The increased rate of congenital malformations with phenytoin may be related to its anti-folic acid effect. Therefore, it is reasonable to recommend folic acid, 0.8–1 mg/day, to all women of childbearing age who take phenytoin anticonvulsants.55 More than 40 years ago, the concern that high supplemental intake of folic acid could adversely affect the effectiveness of anticonvulsant drugs was first raised. Review of the literature by one expert in the area of folic acid supplementation notes that supplementation as high as 1 g/day appears to have no significant impact on seizure activity.19

In the preconception period, there must be a risk/benefit evaluation regarding the need for antiseizure medication and the type and dose of medication. Convulsions in pregnancy are not innocuous. Controversy exists as to whether the disease process, medications to control the seizures, or a combination of both is associated with the increased risk of fetal malformation. It has been recommended that consideration be given to discontinuing antiepileptic drugs in women who have had no seizure activity in at least 2 years56; however, consultation with the patient’s neurologist is essential before offering such a recommendation.

Thrombosis/Hypertension

Some prosthetic cardiac valves require continuous anticoagulation. Coumarin and its derivatives are effective anticoagulants; however, coumarin readily crosses the placenta and has been associated with warfarin embryopathy.57 The syndrome consists of facial dysmorphism, stippled epiphyses, and short stature. Because heparin does not cross the placenta and is not teratogenic, a woman who is taking coumarin derivatives should be guided to change to heparin before conception.

Pregnancy and the postpartum state increase the risk of occurrence and recurrence of thromboembolic disease. Patients with hypercoagulation disorders, such as antithrombin III deficiency, protein C and protein S deficiencies, and anti-cardiolipin antibody syndrome, are at highest risk. Patients who have had recurrent thromboembolic events or a positive family history of thromboembolic disease should be evaluated for these disorders during the preconceptional period because the blood coagulation factors change in pregnancy, resulting in coagulation studies that may be difficult to interpret.

Patients with primary pulmonary hypertension, Marfan’s syndrome with aortic root involvement, coarctation of the aorta, and dilated cardiomyopathy should be counseled before conception that their disease may be made worse or may prove fatal when stressed by the physiologic changes associated with pregnancy.

A patient with known chronic hypertension should have the status of her cardiovascular and renal function assessed and the need for antihypertensive therapy reviewed. Maintaining a systolic blood pressure of less than 140 mmHg and a diastolic blood pressure of less than 90 mmHg by pharmacologic agents or lifestyle modifications—to include weight reduction, increased physical activity, moderation of dietary sodium, and avoidance of smoking—will give the best outcome.58 Except for angiotensin-converting enzyme (ACE) inhibitors, medications for chronic hypertension should continue to be taken before and throughout pregnancy. Fetuses exposed to ACE inhibitors during the second and third trimester have been reported to have a 30% incidence of fetopathy, including renal disease ranging from dysfunction to complete failure.59 Alternate antihypertensive agents, such as methyldopa or calcium channel blockers, should be considered preconceptionally or at least changed during the first trimester of pregnancy and continued throughout gestation.60

Renal Disease

In a patient with chronic renal disease, pregnancy can be considered a reasonably safe option when blood urea nitrogen is less than 30 mg/dL, serum creatinine is less than 3 mg/dL, and diastolic blood pressure is less than 100 mmHg. Because renal function in patients with chronic renal disease generally decreases with age, women with currently good renal function and normal blood pressure who are contemplating pregnancy should be encouraged to try to conceive without unnecessary delays and during the time when they require the least amount of medication. Patients with severe renal insufficiency and hypertension should be aware not only that pregnancy could seriously jeopardize their health but also that there is an increased risk of preeclampsia, preterm delivery, and fetal growth restriction. Patients who have undergone urinary diverting procedures before pregnancy, such as an ideal conduit, enterocystoplasty, or pyeloileoceptomy, usually have relatively uneventful pregnancies except for a higher incidence of pyelonephritis, especially late in pregnancy.61

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) patients should be advised that the best time to attempt conception is during periods of inactive disease. Pregnant patients with active SLE are at significant risk of spontaneous abortion, prematurity, preeclampsia, and fetal growth restriction.62 It is optimal that SLE be inactive for at least 6 months before pregnancy. These patients may continue taking prednisone or azathioprine through the preconceptional period as well as during pregnancy; however, they should be on the lowest possible dose of corticosteroid and/or immunosuppressive therapy before pregnancy. The prepregnancy workup should include an assessment of renal function by 24-hour urine collection for total protein excretion and creatinine clearance, a complete blood count, and evaluation of specific antibodies, such as lupus anticoagulant anti-cardiolipin antibodies and the SS-A (anti-Ro) antibody. Even though patients with inactive SLE have a better maternal outcome, neonatal complications such as neonatal lupus and congenital heart block still occur. Patients who commence pregnancy with evidence of hypertension and lupus nephropathy are at significant risk of having an adverse maternal and fetal outcome.63

Thyroid Disease

Maternal hyperthyroidism is associated with an increased incidence of preterm labor, preeclampsia, and fetal thyrotoxicosis secondary to maternal stimulating immunoglobulin antibody crossing the placenta. Patients should understand that the complications of pregnancy are decreased when compliance with propylthiouracil treatment is maintained before and throughout pregnancy.64 Likewise, patients with hypothyroidism should maintain the dosage of thyroid replacement therapy before and during pregnancy based on the results of laboratory monitoring of thyroid function.65

Multiple Sclerosis

Multiple sclerosis (MS) is a disease of unknown etiology with an increased prevalence in white females between 20 and 40 years of age. The disease is characterized by multiple exacerbations and remissions and variability in severity. The overall effect of pregnancy and the puerperium on the course of MS has been controversial. There is no evidence that pregnancy alters the ultimate outcome in women with MS; however, there appears to be a 20–40% incidence of relapse in the first 3 months postpartum.33 In a study of 153 female MS patients, Runmarker and Andersen66 found that pregnancy protected them from the onset of bouts of MS, that MS occurred less often in parous than in nulliparous women, and that pregnancy after MS onset is associated with a subsequent lower risk of progression. The authors hypothesized that the alterations in the course of MS may be caused by an immunologic change during pregnancy. In the preconceptional counseling of a patient with MS, the current understanding that pregnancy does not appear to affect the overall course of MS should be shared, as well as the potential of relapse during the puerperium. The advisability of identifying family support systems to help with caregiving for both the mother and the baby deserves exploration. Because fertility is unaffected by MS, contraception should be discussed; oral contraceptives are not contraindicated. Although not considered a hereditary disease, MS is common among family members. The children and siblings of MS patients do have an increased risk of MS development. MS occurs in approximately 0.5–1% of the children of MS patients, which is 25 times that expected in the general population; siblings have approximately a 3% chance, which is 76 times that expected in the general population.

Infectious Diseases

RUBELLA.

There has been an increased incidence of congenital rubella syndrome. In a study of 22 women who delivered infants with this syndrome in four Southern California counties, 57% of the women had 22 known missed opportunities, such as induced and spontaneous abortion, for rubella screening and/or vaccination.67 The immune status of all nongravid women should be determined; women can be considered immune to rubella if they have documentation of vaccination with at least one dose of measles–mumps–rubella vaccine or other live rubella-containing vaccine on or after their 1st birthday.68 Individuals whose status is reported as “equivocal” should be considered rubella-susceptible unless they can produce a record of adequate vaccination or previous serologic testing that indicates rubella immunity.68

VARICELLA-ZOSTER VIRUS.

Ten percent of the adult population is nonimmune to varicella-zoster virus (VZV). Adults are more likely to have severe infections, primarily owing to varicella pneumonia. In a multicenter, prospectively controlled study of 106 women with clinically diagnosed VZV infection in the first 20 weeks of gestation, Pastuszak and colleagues69 reported that the congenital defects associated with VZV occurred in 1 infant; the risk of embryopathy was 1.2% if the patient contracted VZV within the first 20 weeks. Fourteen patients contracted VZV after 20 weeks’ gestation, with no evidence of a teratogenic effect. When the authors’ data were pooled with the results from other prospective studies, the mean risk of embryopathy after VZV infection in the first trimester was 2.2%. Currently, varicella virus vaccine live (Varivax) is the first vaccine available in the United States that is effective against VZV. Varivax is a preparation of the live, attenuated virus; it contains the virus in an altered, weakened, virulent form. It is currently recommended that children who are older than 1 year and who have not contracted VZV receive the vaccine. In the preconceptional counseling period, if there is no history of varicella in the patient and if the patient desires, VZV titers can be performed. If no immunity is substantiated, then administration of Varivax could be considered. After the two injections, the efficacy rates in clinical trials indicate a seroconversion rate in 99% of patients older than 13 years. It is recommended that adults avoid salicylates for 6 weeks after vaccination because of the theoretic risk of Reye’s syndrome. It is also recommended that women receiving the vaccine do not become pregnant for 3 months after the vaccination.

MISCELLANEOUS INFECTIONS.

Patients who own cats that are free to wander outdoors or who handle or eat raw meat should be given primary preventive education and methods to minimize the risk of toxoplasmosis; antibody testing may be offered. Assessment of high-risk behaviors and situations may suggest other laboratory testing, such as for human immunodeficiency virus, Treponema pallidum (syphilis), hepatitis, Mycobacterium tuberculosis, Neisseria gonorrhoeae, and Chlamydia. To allay their anxieties, day-care workers could be offered cytomegalovirus and parvovirus antibody testing.

Recurrent Spontaneous Abortions

In a study of 68 women, Aoki and associates70 investigated whether the activity of natural killer (NK) monocyte cells was predictive of subsequent abortion. Women included in the study had histories of two consecutive first trimester abortions, no live births, and no identifiable cause of recurrent miscarriage, such as anti-phospholipid antibodies, uterine anomalies, endocrine abnormalities (including luteal phase defect), or genetic abnormalities. The women with high NK cell activity detected in the nonpregnant state had a significantly higher abortion rate in the next pregnancy than women with normal levels (71% vs. 20%; relative risk 3.5; 95% confidence interval 1.8–6.5). This finding suggests that the preconceptional identification of elevated levels of NK activity may be predictive of subsequent loss. Leukocyte immunization in early pregnancy may prove beneficial to women with elevated levels of NK activity.

Genetics

The relationship between genetics and reproductive outcome relates not only to the ethnic and racial background of the patient but also to the family history. Individual as well as family risk may prompt carrier screening, such as Tay-Sachs testing for Eastern European Jews or French Canadians; β-thalassemia screening for Greeks and Italians; α-thalassemia testing for Indians, Pakistanis, Southeast Asians, and Filipinos; and sickle cell anemia screening for those of African, Mediterranean, and Middle Eastern descent. The most common autosomal recessive disease for North American Caucasians of European ancestry is cystic fibrosis (CF). Carrier screening has only recently been made available for this disease. In October 2001, ACOG released very specific guidelines for CF screeninnong that underscore the importance of the preconceptional period in identifying risk.71 ACOG clinical guidelines recommend that CF screening be offered to all individuals with a family history of CF, to reproductive partners of individuals who have CF, and to couples in whom one or both partners are Caucasian and are planning to become pregnant or who are entering prenatal care. ACOG further recommends that screening be made available to individuals and couples in racial and ethnic groups at lower risk and in whom the test may be less sensitive.

For some couples, such as those with a family history of mental retardation suggestive of fragile X syndrome, unexplainable mental retardation in the family, or Down’s syndrome, preconceptional counseling should include genetic counseling and a discussion of prenatal diagnosis, including its risks and limitations. It is far better to discuss this option in the prepregnancy state than in early pregnancy. In some instances, genetic information may result in a couple deciding to forgo pregnancy.

Psychosocial Issues

Psychosocial assessments should include type of work; number of work hours; potential stressors to the pregnancy, such as use of vibrating machines; and potential teratogenic exposure to heavy metals (e.g. lead, mercury), pesticides, and organic solvents (see next section, Work and Environment). Healthcare and disability insurance may be important family and economic concerns. The patient and her partner should be queried about the use of alcohol, tobacco, and illicit drugs.

Although many women understand the risk of substance exposures after confirmation of pregnancy, they are generally unaware of the importance of the earliest weeks of conception; such women are unlikely to change exposures in a timely manner. The National Household Survey on Drug Abuse (NHSDA) is an annual survey sponsored by the federal government. Included in the survey are 223 pregnant females ages 15–17 years; 1495 pregnant women ages 18–25 years, and 669 pregnant women ages 26–44 years. Recently published data72 found that approximately 12% of pregnant females used alcohol during the month prior to the interview and 3% used illicit drugs. In addition, it was revealed that 23.3% of the respondents drank alcohol in the first trimester compared with 8.8% in the second trimester and 6.0% in the third trimester. “Binge” alcohol use, which is defined as drinking five or more drinks on the same occasion, was reported by 8.8% in the first trimester and declined to 0.6% by the third trimester. Because alcohol use in the first trimester and the resultant fetal alcohol syndrome are the leading cause of preventable mental retardation, the findings of the NHSDA report underscore the need to inquire about alcohol use in all well-woman visits and to provide appropriate education and counseling.

Another NHSDA report reveals that, in 1999, 17% of pregnant women ages 15–44 years used one or more tobacco products (cigarettes, smokeless tobacco, cigars, or pipes) in the month prior to the survey.73 This number compared with 30.5% of the nonpregnant female sample, including those who had a child younger than 1 year. To highlight the importance of routinely addressing the tobacco health risk for women in general, it has been suggested that inquiries about smoking stats be considered the “new vital sign” and routinely included in the clinical assessments of all women, irrespective of reproductive status or intent.74 One advantage of addressing cessation prior to pregnancy is that all of the first-line pharmacotherapies approved by the FDA as safe and effective for tobacco dependence treatment can be used; the nicotine replacement therapies have not been approved for use in pregnancy. For women actively contemplating pregnancy, a new evidence-based office intervention developed for smoking cessation in pregnancy may prove useful.6 The intervention described in an ACOG Educational Bulletin75 describes a five-step counseling approach that has been demonstrated to increase cessation by 30–70%. The specific steps adhere to the “5-A” counseling model of “ask, advise, assess, assist, and arrange.”

In 1994, it was estimated that approximately 4 million women suffered nonfatal violence by an intimate partner and that abuse during pregnancy may affect up to 26% of pregnant women.76 Screening questions directly related to domestic violence should be included in the psychosocial assessment of every woman at all routine and emergency encounters.

The male partner is of great help in supporting lifestyle modifications as they relate to smoking, alcohol, and drug exposures, medications, and exercise. The male’s preconceptional health status may also be of consequence. If an ovum is fertilized by an altered spermatozoon secondary to paternal smoking or alcohol intake, there is a theoretic risk that the pregnancy will result in a spontaneous abortion, a live-born infant with malformations, or a child who appears normal at birth, but is at increased risk for a later disease such as cancer.77 A prospective study of 3891 antenatal patients revealed that 23.6% had not smoked cigarettes during gestation, but had been exposed to sidestream smoke for at least 2 hours daily. Passive smoke exposure was significantly related to delivery of full-term lower-birth-weight infants.78 In analyzing the birth weight of 377 infants with a history of paternal alcohol intake, there was a strong correlation between the father’s alcohol use in the month before conception and the infant’s birth weight. If the father averaged two or more drinks daily or had at least five drinks on one occasion, infant birth weight was reduced by 181 g. A stepwise regression analysis to investigate the effects of other drugs used by each parent predicted that paternal alcohol use reduced birth weight by an average of 137 g.79 Increased paternal age has been observed to be associated with a greater than expected risk for autosomal dominant disease caused by new mutations. The risk that a man older than 50 years will father an offspring with an autosomal dominant disease (e.g. achondroplasia, Marfan’s syndrome, fibrodysplasia ossificans progressiva) caused by a new mutation is 0.3–0.5%.80

WORK AND ENVIRONMENT.

The patient or her partner may be exposed to organic chemicals such as tetrachloroethylene, xylene, styrene, or toluene. Exposure of male workers to some of these organic solvents has been ascertained through questionnaires and biologic monitoring data. Overall, most studies show a fairly consistent association between maternal solvent exposure and spontaneous abortion when high exposure occurs, but investigators have not characterized a dose response. Paternal exposure to organic solvents has not shown an increased incidence of spontaneous abortion in the partners.81, 82 Epidemiologic evidence for the association of paternal exposure to Agent Orange and increased prevalence of offspring with congenital malformations is limited.83

In 1988, Goldhaber and coworkers84 in a case-control study found that women who used video display terminals (VDTs) more than 20 hours per week had a significantly increased rate of abortion compared with women who worked less than 20 hours per week. In another case-controlled study, 628 women known to have experienced spontaneous abortion by 20 weeks’ gestation were compared with 1308 controls; after controlling for many of the variables, the researchers found no apparent relationship between spontaneous abortion and VDT exposure.85 In yet another case-control study, the experiences of women employed as directory assistance operators and general operators at two companies in eight southeastern states were compared. During a 3-year period, 882 women had been pregnant. A spontaneous abortion rate of 14.8% in the exposed group and 15.9% in the nonexposed group was found not to be statistically significant.86 Thus, there appears to be a lack of association in most studies between VDT exposure and spontaneous abortion, but the question has not been definitively answered, because all existing research has been retrospective in design.

To date, there is no convincing evidence to support a relationship between residential electromagnetic field exposure (e.g. electric blankets, heated water beds, ceiling cable heat, and VDTs) and spontaneous abortion. A comprehensive review of the literature regarding this relationship concluded that “laboratory, experimental and epidemiologic results to date have not yielded conclusive data to support the contention that such fields induce adverse reproductive effects under the test or environmental conditions studied.”87

Indeed, little is definitively known about the impact of environmental exposures on pregnancy outcomes.

Women Seeking Preconception Care

Cox and colleagues88 reported their experience with 1075 preconceptional counseling patients seen between 1982 and 1990 at the Queen Mother’s Hospital in Glasgow. Over time, the demand for preconceptional counseling increased dramatically, with 323 new patients in 1990 compared with 96 in 1985. The main categories included previous spontaneous abortion (44.4%), previous fetal abnormalities (19.6%), chronic maternal disease (22.3%), and others (13.7%). Subsequent pregnancy outcome was unchanged in patients with recurrent abortions and fetal abnormalities, but appeared to be improved with the chronic maternal disease group. A significant proportion of patients present with one concern, but notably, an average of three to four other significant risk factors are uncovered during the interview.89 The cost-effectiveness of preconceptional counseling is currently being studied; both the pregnancy outcome and the scientific advice must be continually evaluated.90 Intuitively, primary prevention is the key to a positive maternal and fetal outcome.

SUMMARY

Preconceptional health promotion should provide a prevention framework for interactions with all women of childbearing potential.89 Preconceptional counseling is properly directed by specialists in the field of obstetrics and gynecology, but this does not preclude family practitioners, advanced practice nurses, and others from actively participating in this important focus for primary prevention. The obstetrician/gynecologist not only is involved in acute diagnosis and treatment plans but also is the primary contact for most women of childbearing age. This is an awesome responsibility, as well as an opportunity for disease prevention, education, and counseling on behavior modification. Such care is integral to a comprehensive and coordinated women’s healthcare program.

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