Ethnic Group	Higher Risk	Carrier Frequency
Caucasian	Cystic fibrosis	1 in 25
African American	Sickle cell disease Beta thalassemia	1 in 12
Southeast Asian	Alpha thalassemia	1 in 20
Mediterranean (Italian, Greek)	Beta thalassemia	1 in 25
Ashkenazi Jewish	Tay-Sachs disease Gaucher’s disease type 1 Canavan’s disease Cystic fibrosis	1 in 30 1 in 12 1 in 40 1 in 25

KEY TREATMENT

Folic acid supplementation is 0.4 mg for women without risk factors and up to 4 mg for those with risk factors (SOR: A).

Nutrition

There is sufficient data to confirm that poor nutrition during the prenatal period is associated with adverse pregnancy outcome, specifically intrauterine growth restriction (IUGR) and preterm delivery. Specific nutritional guidelines have been developed based on a woman’s prepregnancy weight or, more specifically, her body mass index (BMI) (Table 21-2). Caloric intake of an extra 300 kcal daily is sufficient for adequate maternal weight gain and fetal growth.

Table 21-2 Recommended Total Weight Gain for Pregnant Women

The practice of prenatal supplementation of vitamins and minerals is widespread, although many nutritionists believe it is unnecessary. Only the following two supplements are recommended in an adequately nourished female with a singleton pregnancy:

1. Iron, 30 mg/day, in the second and third trimester to meet the fetal demands for erythropoiesis.

2. Folic acid, 400 μg/day, in the preconception period and during the first trimester for prevention of birth defects.

However, because many U.S. women do not consume adequate vitamins and minerals (Block and Adams, 1993), and specific assessment of nutritional intake is often difficult, supplements are now widely used. Recommended daily allowances for pregnant women have been established and continue to be reevaluated (Table 21-3). Care must be taken to avoid toxicity of the fat-soluble vitamins, in particular vitamin A (retinol), where “more” is not necessarily better. Daily doses of retinol greater than 10,000 IU, approximately 3000 retinol equivalents (RE), have been associated with birth defects (Rothman et al., 1995). Women who do not consume sufficient milk products may benefit from calcium supplementation. This can easily be accomplished by prescribing an antacid that is made of calcium carbonate, most easily taken in chewable form. This will not only replenish calcium stores but also treat reflux esophagitis, which often occurs in the latter half of pregnancy.

Table 21-3 Recommended Dietary Allowances for Women

Recent data suggest that supplementation with omega-3 fatty acids, specifically docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA), may be beneficial (Dunstan et al., 2008). Both DHA and EPA may be beneficial for fetal brain development and are found in large amounts in wild fish. However, increased fish intake in pregnancy is not recommended because of the risk of increased mercury ingestion. Therefore, supplementation would be required. Large, well-controlled studies are needed before recommendation in pregnancy, but supplementation may be considered on an individual basis. The U.S. Food and Drug Administration (FDA, 2004) has formally warned women of childbearing age, pregnant and lactating women, and young children to avoid eating swordfish, shark, king mackerel, and tilefish and to consume no more than one 6-ounce can of albacore tuna per week. In all pregnant women, nutritional risk factors should be addressed, including low starting BMI, prior LBW infants, adolescence, religious and cultural dietary restrictions, medical illnesses requiring dietary manipulation, substance abuse, and eating disorders (Kolasa and Weismiller, 1995). Certain woman may benefit from formal dietary counseling from a dietician/nutritionist.

KEY TREATMENT

Iron (30 mg/day) is recommended in the second and third trimesters (SOR: A).

Folic acid (400 μg/day) is recommended in the preconception period and first trimester (SOR: A).

Medical Risk Assessment

The preconception period is the ideal time to assess and counsel the prospective pregnant woman regarding medical disorders or risks she may encounter during the pregnancy. Of medical problems that have substantial impact on the fetus, hypertensive disorders and diabetes are among the most common.

Hypertension may have many effects on the pregnancy depending on the degree of abnormality. Fetal effects range from none to increased miscarriage, IUGR, abruptio placentae, and fetal death. Underlying blood pressure disorders should be treated appropriately before pregnancy. Some hypertensive, reproductive-age women are treated with angiotensin-converting enzyme (ACE) inhibitors. This class of therapeutics can cause significant risk to the developing fetus. These medications should be stopped and alternate medications started if needed. Women with preexisting hypertension should be referred for concurrent care with a physician experienced in managing hypertension in pregnancy.

Diabetes can also have many effects on the developing fetus. The preconception control of the maternal metabolism, reflected as normal blood glucose values before and after meals and normal hemoglobin A_1c, has been shown to decrease the incidence of diabetes-associated embryopathy to almost that of a nondiabetic pregnant woman (Mills et al., 1988). Women with preexisting diabetes should be referred for specialized care if pregnancy is contemplated.

Less attention is directed to emotional and psychiatric disorders. Pregnancy may be a stressor that precipitates an acute event or worsens ongoing anxiety or depression. This is more likely in the postpartum period.

KEY TREATMENT

Preconception care is an integral part of prenatal care and permits health promotion and early identification of risk factors that can then be treated before pregnancy, such as diabetes or hypertension (SOR: A).

Women with preexisting diabetes should be referred for specialized care if pregnancy is contemplated (SOR: C).

Routine Prenatal Care

In most Western countries, women attend between 7 and 11 prenatal visits, although recent data suggest that a reduced number of antenatal visits could be introduced into clinical practice without adverse effect to the mother and child (Carroli et al., 2001). Obstetric care provided by obstetricians, family physicians, and midwives has been found to be equally effective; however, patients were slightly more satisfied by the care provided by midwives and family physicians (Villar et al., 2004). Prenatal care services typically include screening and treatment for medical conditions and identification and interventions for behavioral risk factors associated with poor birth outcomes (e.g., smoking, poor nutrition).

One of the most important goals of prenatal care is recognizing which women have high-risk pregnancies and triaging these women to appropriate care (Kontopoulos and Vintzileos, 2004). It is important to identify the women at risk for adverse outcomes and refer them to appropriate specialty care. Adequate prenatal care has been shown to increase the chances that a woman has a healthy pregnancy and baby.

First Prenatal Visit

The first prenatal visit is one of the most important, particularly if the woman has not had preconception care (Box 21-3). The first prenatal visit should occur shortly after the woman discovers she might be pregnant and should be viewed as a continuation of preconception counseling. Home pregnancy test kits have a sensitivity and specificity of at least 95%; many can detect pregnancy by the fifth menstrual week. The most important aspects of the first prenatal visit include education, risk assessment, appropriate laboratory testing, and establishment of gestational age.

Box 21-3 Expert Panel Recommendations for First Prenatal Visit

From Rosen M, Merkatz I, Hill J. Caring for our future: a report by the expert panel on the content of prenatal care. Obstet Gynecol 1991;77:785.

Risk Assessment for All

Medical History

Medical/surgical update

Nutrition update

Current pregnancy to date ^∗

Psychosocial History

Extremes of physical work, exercise, and other activity

Stress

Physical Examination

Blood pressure ^∗

Weight

Breast examination ^∗

Pelvic examination for uterine size, dating, abnormalities ^∗

Laboratory Tests

Recommended for all:

Hemoglobin/hematocrit

Urine culture

Recommended for some:

^∗ Accepted by panel but not specifically reviewed.

Education is an important component of prenatal care, particularly for women who are pregnant for the first time. Frequency of prenatal visits should be explained, with information about the physiologic changes that occur during pregnancy. Preparation for the birthing process is a key theme around which to discuss care issues and choices such as breastfeeding. Structured educational programs to promote breastfeeding have unclear effectiveness. Pregnant women should be counseled about the risks of possible teratogens, including smoking, alcohol, and drug use, including exposure to medications, prescriptions, OTC drugs, and herbal remedies. Good handwashing is always encouraged because this is one of the best ways to avoid community-acquired infectious diseases. Appropriate immunizations such as influenza and novel influenza A (H1N1) virus should be offered. Common exposures such as workplace conditions and use of hot tubs and saunas should be explored. Exercise should also be encouraged if there is no obstetric contraindication (Box 21-4). Intercourse during pregnancy should be actively addressed because some women are reluctant to discuss this topic even with their physician. Sexual activity can generally continue during pregnancy except for few situations, such as placenta previa and preterm labor. Counseling regarding sexually transmitted diseases (STDs) and their avoidance should occur. Nutrition should be individualized, with an estimate of desirable weight gain given to the pregnant woman.

The estimated date of delivery (EDD) should be calculated by accurate determination of the last menstrual period (LMP). The first day of the LMP is a good clinical sign from which to calculate EDD, remembering that it must be adjusted for cycles shorter or longer than 28 days. The EDD can be calculated by Nagle’s rule, that is, subtracting 3 months and adding 7 days to the first day of the LMP. EDD should then be extended by the number of days longer than a 28-day cycle or shortened by the number of days shorter. This approach should be considered if there is uncertainty about the LMP.

The physical examination during the first prenatal visit should include careful assessment of uterine size. If there is a discrepancy between menstrual age and uterine size, ultrasound should be considered early in the pregnancy to resolve the issue of dating. Recent evidence suggests that early sonography provides more accurate dating, which is important for timing screening tests and interventions and for optimal management of complications such as post-term pregnancies (Neilson, 2004). Late ultrasound, after 24 weeks, is not as sensitive for confirming gestational age. Additionally, any irregular bleeding or abdominal pain should prompt the practitioner to obtain sonographic confirmation of viability of the pregnancy as well as its normal intrauterine location.

A history and directed physical examination should be performed to detect conditions associated with increased maternal and perinatal morbidity and mortality. The first prenatal examination provides an opportunity for cervical cancer screening with a Papanicolaou (Pap) test in women who have not been screened recently. However, Pap tests performed in pregnant women may be less reliable. Risk factors should then identify other testing that might be done at this time, including blood glucose, sickle cell screening, Tay-Sachs screening, and surveillance for other infectious diseases.

Routine fetal heart auscultation, urinalysis, and assessment of maternal weight, blood pressure, and fundal height generally are recommended, although the supportive evidence varies (Kirkham et al., 2005). Women should be offered ABO and Rh blood typing and screening for anemia during the first prenatal visit. Genetic counseling and testing should be offered to couples with a family history of genetic disorders, a previously affected fetus or child, or a history of recurrent miscarriage. All women should be offered prenatal serum marker screening for neural tube defects and aneuploidy. Women at increased risk for aneuploidy should be offered amniocentesis or chorionic villus sampling (CVS). Counseling about the limitations and risks of these tests, as well as their psychologic implications, is necessary. Folic acid supplementation beginning in the preconception period and early pregnancy reduces the incidence of neural tube defects. Laboratory testing during the first prenatal visit consists of assessment of hemoglobin and hematocrit to identify anemia; blood D(Rh) type; serologic tests for syphilis, and rubella immunity; hepatitis B, and urinalysis. Testing for human immunodeficiency virus (HIV) infection should be offered and highly recommended because perinatal transmission can be decreased with appropriate medical intervention. During the pelvic examination, a Pap smear (if not done in past 6 months) as well as cultures for Neisseria gonorrhoeae and Chlamydia should be taken.

Follow-up Prenatal Visits

According to the report of the Expert Panel on Prenatal Care (Rosen et al., 1991), low-risk primigravid women should have at least 10 prenatal visits; low-risk multiparous women should have at least eight visits. Again, however, data suggest that antenatal visits could be reduced without adverse effect to the mother and child (Carroli et al., 2001). Women with psychosocial issues or pregnancy complications should be seen more frequently. In the first two trimesters, prenatal visits may be 5 to 6 weeks apart if no problems have been ascertained. Frequency of visits should increase after 30 weeks, with weekly visits after 37 weeks. Specific recommendations are noted in Table 21-4. Routine visits for low-risk women should be scheduled at times that recommended laboratory testing could be accomplished. Prenatal screening for chromosomal abnormalities is available in the first trimester between 10 weeks, 2 days and 13 weeks, 6 days. Structural defects of the fetus (in particular neural tube defects) and karyotypic abnormalities in the form of alpha-fetoprotein based tests (Quad screen, see below) can be obtained at 16 to 18 weeks. Screening for gestational diabetes is recommended at 26 to 28 weeks of gestation, as well as screening for anemia with a hemoglobin or hematocrit. Antibody screening, Rh₀(D) immune globulin (RhoGAM) prophylaxis for D-negative mothers, and repeat testing for infectious diseases for at-risk mothers are recommended at this time.

Table 21-4 Expert Panel Recommendations for Visits throughout Pregnancy

Activity	Week/Trimester
Check for any exposure to infection.^∗
Physical Examination
Blood pressure	24^†
Weight	Each visit
Fundal height/growth	16^†
Fetal lie/presentation/engagement/heart rate^∗	24^†
Cervical examination	41^∗
Laboratory Tests
Hemoglobin/hematocrit	24-28
Rh sensitivity^‡	26-28
Diabetic screen	26-28
Repeat syphilis^‡	Third trimester
Repeat gonococcal and HIV^‡	36
Serum alpha fetoprotein	14-16
Ultrasound∗	When indicated
Health Promotion Activities
Teratogen avoidance	Each visit
Safer sex^∗	Each visit
Maternal seatbelt use	Each trimester
Smoking cessation^‡	Each trimester
Work/nutrition counseling^‡	Each visit
Signs of preterm labor	Second/third trimester
Physical/emotional changes^∗	First/third trimester
Sexuality counseling^∗	Last half of pregnancy
Fetal growth/development	Each visit
Self-help for discomforts^‡	Each visit
General health habits	Each visit
Breastfeeding	26^†
Infant car seat safety	Each visit
Childbirth/parenting classes	32
Family roles adjustment	38
Information about laboratory tests^∗	Before testing
Birth plan^∗	Third trimester
Labor (when to call/where to go)^∗	Third trimester

HIV, Human immunodeficiency virus.

∗ Accepted by panel but not specifically reviewed.

† That week and each week thereafter.

‡ For some.

From Rosen M, Merkatz I, Hill J. Caring for our future: a report by the expert panel on the content of prenatal care. Obstet Gynecol 1991;77:785.

At 36 weeks’ gestation, rectocervical cultures for group B streptococci (GBS) should be obtained. If cultures are positive, antibiotic prophylaxis during labor is given. For women without a penicillin allergy, penicillin (5 million units, then 2.5 million units IV every 4 hours) is administered during labor. If there is a penicillin allergy, sensitivities to clindamycin and erythromycin should be obtained and one of these agents used. If the organism is resistant to these antibiotics, women with a serious penicillin allergy should receive vancomycin; women with a minimal reaction from penicillin (e.g., rash) should receive a first-generation cephalosporin intravenously during labor (ACOG, 2002a, Schrag et al., 2002). Women with GBS bacteruria or a prior child affected with GBS sepsis should be treated during labor without screening cultures.

The clinical components of routine prenatal visits are controversial. Most guidelines recommend routine assessment with fundal height and maternal weight and blood pressure measurements, fetal heart auscultation, urine testing for protein and glucose, and questions about fetal movement. The assessment of uterine growth and size should be performed at every prenatal visit. Documentation of fetal heart tones is also recommended with each prenatal visit. Before 12 weeks’ gestation, the size of the uterus is estimated by bimanual pelvic examination. The ability to assess the presence of fetal heart tones using Doppler ultrasound before 12 weeks is variable. After 12 weeks and before 20 weeks, adequate uterine growth is assessed by location of the uterine fundus in the lower abdomen (Fig. 21-2). Fetal heart tones should be reliably heard during this period. At 20 weeks of gestation, most women have a palpable fundus at the umbilicus. After 20 weeks, fundal height is measured using the distance from top of the symphysis pubis to top of the fundus. The number of completed weeks of gestation should equal this measurement in centimeters (±2 cm). This measurement should be performed as accurately as possible. The most common reasons for inconsistency between menstrual age and fundal height is an inaccurate menstrual-age assignment and inaccurate measurements caused by maternal obesity. Larger-than-expected fundal height may also be caused by multiple gestation, uterine fibroids, polyhydramnios, or a large-for-gestational-age (LGA) fetus. Smaller-than-expected fundal height should warrant an exploration for etiologies such as oligohydramnios, IUGR, and fetal demise.

Figure 21-2 Fundal growth at various weeks of gestation.

By 30 weeks’ gestation, the fetus is large enough that it can be palpated through the maternal abdomen. Position of the fetus should be documented at this and subsequent visits. This is easily done in most women by Leopold’s maneuvers (Fig. 21-3). The first maneuver involves palpation of the uterine fundus to identify the fetal part that is there. The palpating hands then glide downward laterally to perform the second maneuver, location of the fetal back. In the third maneuver the hands are cupped around the presenting part at the level of the symphysis pubis to determine the presenting part as well as its degree of descent into the pelvis. If the presenting part is cephalic, the fourth maneuver will determine its degree of flexion. The examiner now turns 180 degrees to face the mother’s legs, and the cephalic prominence is palpated. Another aid in ascertaining the position of the fetal back is the location of the fetal heart tones by Doppler sonography or auscultation. These sounds are best heard through the fetal back; in the left lower uterus in left occiput anterior, transverse, and posterior positions of the fetal head; and the right lower uterus in right occiput positions. The evidence supporting the previous practices is variable but continues as the standard of care (Kirkham et al., 2005).

Figure 21-3 Leopold’s maneuvers for determination of fetal position. A, First maneuver: palpation of the uterine fundus to identify the fetal part. B, Second maneuver: location of the fetal back. C, Third maneuver: cupped hands to determine the presenting part and station. D, Fourth maneuver: palpation of the cephalic prominence to determine the degree of flexion.

By the end of gestation, the practitioner as well as the woman should know the presentation of the fetus. This avoids emergent management when she presents in labor with a nonvertex presentation. Internal digital cervical examination can also verify presentation of the fetus and may be done when needed. Unless indicated, however, routine cervical examination to determine cervical readiness for labor need not be done until 41 weeks’ gestation.

Prenatal Genetic Diagnostic Testing

If specific risk factors for fetal abnormalities are identified in the mother, appropriate counseling and specific diagnostic testing should be offered. The most common reason to offer prenatal genetic diagnosis is advanced maternal age; a somewhat linear increase in nondisjunction in meiosis increases the risk of a conception with aneuploidy (abnormal chromosome number). This is one reason why older women have a higher rate of spontaneous first-trimester miscarriage. It is also why older women are more likely to give birth to a child with a chromosomal abnormality, most often Down syndrome (trisomy 21).

Women of advanced maternal age are those 35 or older at the anticipated birth of their baby. This group of women should be given specific counseling and offered diagnostic testing in the form of amniocentesis or CVS to ascertain the well-being of their fetus.

Amniocentesis

Genetic amniocentesis is typically performed at 14 to 20 weeks of gestation but can also be done any time after 20 menstrual weeks. After ultrasound examination of the fetus and placenta, an area of skin overlying a pocket of amniotic fluid is cleaned with iodine solution. With ultrasound guidance throughout the procedure, a 22-gauge spinal needle is used to remove 20 mL of amniotic fluid. Special care is taken to avoid the fetus, umbilical cord, and the large placental vessels. In experienced hands, the pregnancy loss rate attributed to the procedure is about 1 in 300. The entire testing time for a chromosomal analysis is about 10 to 12 days. Alternately, the supernatant may be assayed for metabolites to diagnose other disorders that run in the family if identified on counseling. Earlier amniocentesis (at 11 to 13 weeks) has been successfully performed but is not recommended any longer because of the recent initial reports regarding a slightly higher rate of clubfoot in these newborns.

Chorionic Villus Sampling

In CVS, another technique for obtaining fetal tissue for genetic evaluation, the chorionic villi, or placental cells, are aspirated. With ultrasound guidance, CVS can be performed at 10 to 13 menstrual weeks transabdominally with a spinal needle or transvaginally with a catheter designed and approved for this purpose. Chromosomal analysis of the villous cells can be completed in 7 days. Thus the advantage to CVS is the early gestational time of the procedure and availability of the results. The procedure-related fetal loss rate is approximately 1 in 125 tests (Jackson et al., 1992).

Maternal Biochemical Screening

Low-risk women can be offered screening for genetic abnormalities of the fetus by biochemical testing in the first or second trimester and ultrasound nuchal translucency screening (first trimester) and targeted ultrasound evaluation of fetal anatomy, best done at 18 to 20 weeks’ gestation. The general consensus is that women of any age should have access to any screening or diagnostic testing (as previously described) if they choose to accept the underlying risks.

Biochemical testing is the measurement of certain chemicals in the mother’s blood found to be predictive of fetal abnormality. The quadruple screen is a maternal blood test in which one maternal sample drawn at 15 to 20 weeks (but most sensitive at 16 to 18 weeks) is assayed for alpha fetoprotein, estriols, and beta subunit of human chorionic gonadotropin (hCG). Normal ranges vary for each gestational week. Maternal serum alpha-fetoprotein (MSAFP) elevations can result from open neural tube defects such as spina bifida or anencephaly, when the protein leaks from the fetal tissue into the amniotic fluid through the amniochorion and into the maternal system. A lower-than-expected MSAFP suggests Down syndrome. The addition of β subunit of hCG and estriols has improved sensitivity for the detection of chromosomal abnormalities (Table 21-5). This test should be offered to any pregnant women with appropriate counseling regarding sensitivity and specificity. Women with abnormal tests should be referred for targeted ultrasound and possibly amniocentesis.

Table 21-5 Second-Trimester Quadruple-Screen Results

First-trimester ultrasound and biochemical screening are now available for clinical use, specifically the “First Trimester Screen” performed between 10 weeks, 2 days and 13 weeks, 6 days of gestation. Testing involves an ultrasound measurement of the nuchal translucency (lymphatic fluid at fetal neck) (Fig. 21-4) and laboratory measurement of pregnancy-associated plasma protein A (PAPP-A) and β subunit of hCG. The First Trimester Screen has about 85% sensitivity for Down syndrome detection at 4% false-positive rate. Several tests are also available that combine a first-trimester screen with a second-trimester screen for even higher sensitivity. Physicians should become familiar with the sensitivity, specificity, and availability of the test most suitable for their practices.

Figure 21-4 Transabdominal ultrasound assessment of nuchal translucency (NT). The measurement in this figure is normal. An increased measure (>3 mm) is associated with an increased risk of chromosomal abnormalities, complex congenital heart disease, and other genetic syndromes.

EVIDENCE-BASED SUMMARY

• First-trimester screening using both nuchal translucency measurement and biochemical markers is an effective screening test for Down syndrome in the general population (SOR: A).

• Women found to have increased risk of aneuploidy with first-trimester screening should be offered genetic counseling and the option of chorionic villus sampling or second-trimester amniocentesis (SOR: A).

Drug and Chemical Exposures in Pregnancy

Pregnant women frequently ask about the effect of drug and other chemical exposures on the unborn infant, whether environmental, OTC, or prescription. Many of these are everyday exposures at the workplace, in the community, or as a result of medical treatment and management. The consequences can range from the most innocuous to actually jeopardizing the pregnancy. The physician should be prepared to answer these pregnancy-related questions and advise their patients appropriately.

The consequences of a chemical exposure may be related to the nature of the agent and the timing, dose, and duration of the exposure. The effect can range from minor morphologic abnormalities and growth deficiency to severe malformation and loss of the pregnancy. Thalidomide has obvious effects on the fetus, causing a third of fetuses to have limb reduction defects. Furthermore, the effect of a drug may be subtle or delayed (Welch et al., 1993). Diethylstilbestrol (DES) is associated with the development of uterine structural abnormalities and clear cell carcinoma of the vagina in daughters whose mothers took this medication.

Much of the knowledge about chemical exposures and effects on reproduction and fetal development comes from research on experimental animals. This poses great uncertainty given genetic variability and species-specific responses. Given these limitations, the health care provider must carefully weigh the evidence before using a drug. To help the practitioner classify a drug for use, the U.S. Food and Drug Administration (FDA, 1980) developed a risk factors index. The abbreviated definitions of these categories are as follows:

Category A: Controlled studies in women fail to demonstrate a risk to the fetus.

Category B: Animal reproduction studies have not demonstrated a fetal risk, but there are no controlled studies in pregnant women; or animal reproduction studies have shown adverse effect that was not confirmed in controlled human studies.

Category C: Studies in animals have revealed adverse effects on the fetus, and there are no controlled studies in women. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Category D: There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable.

Category X: Studies in animals or humans have demonstrated fetal abnormalities, or there is evidence of fetal risk based on human experience. The drug is contraindicated in women who are or who may become pregnant.

This classification is an oversimplification, and the individual practitioner will need to weigh the available data in the management of the pregnant woman. Few absolutes are possible in the field of human teratology; however, current recommendations for common drug categories in pregnancy are summarized in Table 21-6. It is important to emphasize that it is difficult to demonstrate an actual cause-effect relationship between a specific drug and an adverse pregnancy outcome. At no time, however, should a drug be considered safe because no data exist.

Table 21-6 Drugs and Exposures in Pregnancy

Agent	Recommendation	Comments
Antihistamines	Acceptable	Most are category B.
Decongestants	Acceptable	Pseudoephedrine preferred.
Cough medication with guaifenesin	Acceptable	—
Acetaminophen	Acceptable	Preferred analgesic and antipyretic.
Aspirin	Avoid	Increases risk of bleeding; no benefit in preeclampsia; may be prescribed in low doses for specific conditions.
NSAIDs	Avoid	Premature closure of ductus arteriosus.
Cephalosporins	Acceptable	—
Sulfonamides	Avoid in third trimester.	Kernicterus in newborn.
Tetracyclines	Avoid	Discoloration of teeth.
ACE inhibitors	Avoid	Stillborn, renal abnormalities, renal failure in newborn.
Immunizations	Avoid live, attenuated viruses.	Measles, mumps, rubella.
Allergy shots	Acceptable	Alteration in maintenance dose may be necessary.