1. Recommendations for screening and management of abnormal cervical cytology in pregnancy follow from the general guidelines for screening onset and frequency that were updated in 2012 to reflect the recommendations of the American Cancer Society ACOG, and U.S. Preventive Services Task Force for detection of cervical cancer. Routine pap screening should not be collected until age 21 regardless of first vaginal intercourse. The risk of severe dysplasia or cancer is very low among adolescents, but they should be encouraged to receive human papilloma virus (HPV) vaccination and counseled about safe sex practices to limit exposure to sexually transmitted infections. Women between the age of 21–29 years should be screened with cervical cytology alone. Women >30 years of age should be screened with cytology and HPV testing every 5 years (or with cytology alone every 3 years). Women with a history of cervical cancer, HIV or other risk factors (such as immunocompromise) should continue annual screening. These guidelines and the associated algorithm are based on a large database of patients including adolescents who were managed using former criteria in the Kaiser Healthcare system. The American Society of Colposcopy and Cervical Pathology (ASCCP) has developed an updated free App that can assist with the current recommendations.
2. Women who have risk factors for cervical/vaginal cancer (such as a history of in utero diethylstilbestrol (DES) exposure, HIV, women who are immunocompromised, or those on chronic steroids) should be screened annually.
3. Women aged 21–29 with normal cytology but absent or insufficient endocervical–transformation zone elements can continue regular screening, which should not include HPV testing. In women >30 years with a similar cytology result, HPV testing is recommended. Positive HPV results should prompt repeat co‐testing in one year, unless the HPV genotype is known to be 16 or 18, in which case, immediate colposcopy is recommended. A negative HPV result in a woman >30 years means that she can go back to routine screening.
4. Unsatisfactory cytology is less common in current practice with the use of liquid‐based media for cervical screening. Insufficient squamous cells to detect epithelial abnormalities generally arise from blood or inflammation that obscures the result. Repeat cytology is recommended in 2–4 months. Colposcopy can be considered in women >30 years with positive HPV, and is recommended in those women who have had two consecutive unsatisfactory cytology test results.
5. Women should always be informed of an abnormal Pap result by her physician or another healthcare professional who can answer basic questions and allay anxiety. Verbal notification should be followed with written information and clear recommendations for follow‐up. Additionally, if there is evidence of infection along with cellular abnormalities, the infection should be treated.
6. The 2012 criteria substantially clarify the management of ASCUS, which is guided by HPV test results whether obtained reflexively or as a co‐test. The management in pregnancy differs only in that colposcopy and endocervical curettage (ECC) should be deferred until 6 weeks postpartum unless a CIN 2+ lesion is suspected. Women >25 years old with a negative HPV test should be returned to a regular three‐year follow‐up cycle. Following pregnancy colposcopy is recommended in women who are HPV+ with annual co‐test follow‐up. Similarly, an endocervical curettage (ECC) should be obtained whenever possible and excisional procedures should be avoided to prevent over‐treatment. In women 21–24 years old, cytology should be repeated in one year. A positive HPV result does not change the recommended follow‐up, but a negative result should return the woman to a three‐year follow‐up cycle.
7. Atypical squamous cells cannot exclude high‐grade squamous intraepithelial lesions (HSIL) (ASC‐H), which is associated with a higher risk of CIN 3+ regardless of patient age and a five‐year invasive cancer risk of 2% regardless of HPV status. That said, HPV is highly correlated with ASC‐H, but the cancer risk demands that all women receive immediate colposcopy, including those 21–24 years of age. Colposcopy with directed biopsies of any area that might be concerning for micro invasion should be done by a highly trained clinician. Treatment should be dictated by histologic evaluation of the biopsied lesions.
8. Atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) warrant aggressive investigation and close follow‐up. Although the risk of cancer is lower in younger age groups, women >30 years have a 9% risk of CIN3+ and 2% risk of invasive cancer. All such women of all ages should have antenatal colposcopy with 6‐weeks postpartum follow‐up to include colposcopy, ECC and endometrial biopsy (EMB). Subsequent treatment and follow‐up are dictated by the biopsy results, maternal age, and the histologic evaluation of the glandular elements.
9. Approximately 60% of low‐grade squamous intraepithelial lesions (LGSIL) will regress spontaneously without treatment depending on the age of the patient, HPV status, and HPV genotype. For women >25 years old in whom HPV testing is negative, repeat co‐testing in ome year is preferred but colposcopy is acceptable. However, if the HPV is positive, then colposcopy is preferred. If colposcopy is not part of the initial evaluation, subsequent co‐testing needs to be entirely normal to allow patients to return to three‐year follow‐up. Any abnormality at the one‐year follow‐up visit should result in colposcopy. In women 21–24 years old, annual repeat cytology without HPV testing is preferred and colposcopy should be avoided unless the results recur for two consecutive years or if one of the following lesions is detected: ASC‐H, AGC, or HSIL. Pregnant women >25 years old with low‐grade squamous intraepithelial lesions should undergo immediate colposcopy without ECC, while those 21–24 years old should be evaluated postpartum.
10. High‐grade squamous intraepithelial lesions (HGSIL) are associated with a 60% risk of CIN2+ and a 2% risk of invasive cervical cancer. Immediate colposcopy with directed biopsies of any area that might be concerning for micro invasion is recommended, regardless of maternal age. The antepartum diagnosed of HGSIL should prompt a 6‐weeks postpartum follow‐up colposcopy with ECC and treatment as dictated by the biopsy results. If diagnosed early in pregnancy, colposcopy can be repeated every 12 weeks. Treatment during pregnancy should be reserved for invasive carcinoma and should be managed in concert with a gynecologic oncologist.

1. Immunization can be active (vaccines, toxoid) or passive (immunoglobulin, antiserum/antitoxin). In active immunity, the immune response is induced by wild infection or vaccination, which is generally robust and long‐lasting. As such, subsequent exposure to the vaccine‐preventable infection will result in the release of antibodies and the prevention of illness. In passive immunity, antibodies are acquired passively through maternal transfer across the placenta or breast milk or through the receipt of exogenous immunoglobulins. Protection is temporary and fades within a few weeks to months. The immune system of the recipient is therefore not programmed, and subsequent exposure to vaccine‐preventable infections can lead to active infection.
2. Vaccination works by inducing antibodies in recipients that protects them against infection after future exposure to specific disease‐causing microbes. The level of protection varies according to the strength and durability of the immune response induced by the vaccine as well as the virulence, prevalence, and ease of transmission of the infection itself. Vaccination programs may have different goals: (i) to protect at‐risk individuals (e.g., meningococcal disease); (ii) to establish control by minimizing the overall prevalence of the infection (e.g., measles, varicella); or (iii) to attain global elimination of an infection (e.g., neonatal tetanus, polio).
3. Vaccination in pregnancy is of benefit and at times poses concern relative to the increased vulnerability of the mother and fetus. Inactivated vaccines are approved for use in pregnancy. The inactivated influenza vaccine should be given to all pregnant women during the influenza season (October through May in the northern hemisphere), regardless of gestational age. It is clear that there are significant maternal benefits including fewer cases of fever and respiratory illness and substantial neonatal protection through the transplacental passage of antibodies that provide months of protection at a time when the infant is vulnerable and could not be directly vaccinated. However, live‐attenuated vaccines (including rubella, MMR, varicella) are not recommended for pregnant women despite the fact that no cases of congenital anomalies have been documented. Exceptions include yellow fever and polio, which can be given to pregnant women when traveling to high prevalence areas. In addition, women should be advised not to get pregnant within 1 month of receiving a live‐attenuated vaccine. The live‐attenuated influenza vaccine is available as an intranasal spray, which is considered safe in the postpartum period. Vaccines considered safe in pregnancy include tetanus, diphtheria, hepatitis B, and influenza. Tetanus immunization during pregnancy is a common strategy used in the developing world to combat neonatal tetanus
4. Risk factors for specific vaccine‐preventable illnesses include:
   • illicit drug users (hepatitis A and B, tetanus)
   • men who have sex with men (hepatitis A) or >1 sexual partner in the past 6 months (hepatitis A, human papilloma virus)
   • travel to or immigration from areas where infection is endemic (hepatitis A and B, measles, meningococcus, rubella, tetanus, varicella)
   • healthcare workers (hepatitis B, influenza, varicella)
   • nursing home residents (meningococcus, pneumococcus, varicella) or ≥50 years of age (influenza)
   • chronic medical diseases: diabetes, asthma, HIV, liver disease and/or renal disease (hepatitis A, influenza, pneumococcus)
   • adults who have had their spleens removed (meningococcus, pneumococcus)
   • accidental or intentional puncture wounds (tetanus)
5. One of the ongoing controversies about vaccination in pregnancy is whether vaccines containing thimerosal pose a risk to the fetus. Thimerosal is a mercury‐containing preservative that has been used in multidose vaccines since the 1930s. Although there has been concern about the cumulative levels of mercury, the current scientific evidence does not consider thimerosal to be associated with adverse outcomes in children exposed in utero. The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) does not recommend avoiding thimerosal containing vaccines. Although the ACIP does not recommend any specific formulation, there are newer trivalent and quadrivalent influenza vaccines (containing two A and two B influenza strains) that are available for use. The following adult vaccines are thimerosal‐free: Tdap (but not Td), Recombivax hepatitis B vaccine (but not Engerix‐B), and some influenza vaccines (Fluzone with no thimerosal).
6. Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) may be given at any time of pregnancy or the postpartum period but ideally is administered between 27–36 weeks to confer the best passive immunity through the transfer of antibodies to the fetus. This recommendation has developed to address the significant impact of pertussis disease in the newborn.

1. Fetal organogenesis occurs before most women are aware that they are pregnant. As such, the ideal time for addressing primary prevention of reproductive health risks is in the preconception period. Since approximately half of all pregnancies in the United States are unplanned, all women of reproductive age should be considered candidates for discussion of these issues.
2. Discuss social, financial, and psychological issues in preparation for pregnancy.
3. Maternal alcohol use is the leading known cause of congenital mental retardation and is the leading preventable cause of birth defects in the Western world. An accurate drinking history is best elicited using a tool that employs standardized screening questions (such as the CAGE questionnaire). The adverse effects of alcohol may be compounded with abuse of other drugs. Cigarette smoking, cocaine, and other drug use should be included in the history. Patients at risk should be provided education, contraceptive counselling, and referral for treatment as necessary.
4. Screen for domestic violence. Be aware of available state and local resources and state laws regarding mandatory reporting. Risk increases with pregnancy. Domestic violence is not isolated to any particular risk group in pregnancy; it cuts across socio‐economic and ethnic lines.
5. Take an occupational history that will allow assessment of workplace risks to the pregnancy. Elicit information about any exposures to hazardous materials or biologic hazards (HIV, cytomegalovirus (CMV), toxoplasmosis) and review the use of safety equipment. Talk to patients about the appropriate and correct use of seat belts while in a moving vehicle.
6. Counsel patients with a history of preeclampsia, placental abruption, unexplained fetal death, or severe intrauterine growth restriction (IUGR) about the risks of recurrence. Low‐dose aspirin starting at the end of the first trimester is recommended to prevent recurrent preeclampsia. The use of low‐dose aspirin, calcium supplementation, and/or anticoagulation for women with documented inherited thrombophilias to prevent adverse pregnancy outcome is controversial, and cannot be routinely recommended.
7. Personal and family histories should be examined for evidence of genetic diseases. Genetic testing is available to determine a patient’s carrier status for some autosomal recessive conditions such as Tay–Sachs, Canavan disease, sickle cell disease, and the thalassemias. Consider referral for further genetic counselling if patients are at high risk. ACOG currently recommends that all couples be offered prenatal testing for cystic fibrosis. ACMG (but not ACOG) recommends that all couples also be offered genetic testing for spinal muscular atrophy (SMA).
8. Emphasize the importance of nutrition. Assess appropriateness of patient’s weight for height, special diets and nutrition patterns such as vegetarianism, fasting, pica, bulimia, and vitamin supplementation. Recommend folic acid supplementation as necessary: 0.4 mg per day for all pregnant women or women considering pregnancy, 4.0 mg per day if the woman has a personal/family history of a child with a neural tube defect or is on anticonvulsant medications (especially valproic acid). Counsel to avoid oversupplementation (such as vitamin A). Review the recommendations on dietary fish ingestion (<12 ounces per week of cooked fish) to minimize mercury intake, and steps for prevention of listeriosis (avoiding raw or undercooked meat/fish, unpasteurized milk and soft cheeses, unwashed fruit and vegetables) and toxoplasmosis (exposure to cat feces).
9. A thorough immunization history should be obtained that addresses vaccination. Women should be tested for immunity to rubella and vaccinated prior to pregnancy if not immune. Women without a history of chickenpox (varicella) should be tested and offered vaccination prior to pregnancy. Hepatitis B vaccination should be offered to all women at high risk, and screening for other sexually transmitted infections should be offered as needed. The U.S. Centers for Disease Control and Prevention (CDC) recommends that pregnancy be delayed for at least 1 month after receiving a live‐attenuated vaccine (such as MMR, varicella, live‐attenuated influenza, BCG).
10. Discuss birth spacing and the options available for postpartum contraception.
11. Effects of the pregnancy on any medical conditions for both mother and fetus should be discussed. Pregnancy outcomes can be improved by optimizing control of chronic medical conditions prior to pregnancy (such as glycemic control in patients with diabetes and blood pressure control in patients with hypertension). Medications should be reviewed, and patients counselled regarding alternatives that may be safer in pregnancy. Close communication with the patient’s primary care and subspecialty physicians should always be maintained.

1. The goal of prenatal care is to promote the health and well‐being of the pregnant woman, fetus, infant, and family up to 1 year after birth. To achieve these aims, prenatal care must be available and accessible. The three major components are: (i) early and continuing risk assessment, including preconception assessment (see Chapter 3, Preconception Care); (ii) continued health promotion; and (iii) both medical and psychosocial assessment and intervention.
2. Routine prenatal tests that should be completed for all pregnant women include complete blood count (CBC), blood group type and screen (Rh status), rubella serology, HIV, hepatitis B, syphilis serology (VDRL/RPR), Pap smear, cystic fibrosis (CF) carrier status, chlamydia/gonorrhea cultures, and urine culture and sensitivity (UA C&S).
3. Approximately 20% (1 in 5) of pregnancies are considered high risk. Risk factors for adverse pregnancy outcome may exist prior to pregnancy or develop during pregnancy or even during labor (examples are listed below, although this list should not be regarded as comprehensive).
4. The frequency and timing of prenatal visits will vary depending on the risk status of the pregnant woman and her fetus. In low‐risk women, prenatal visits are typically recommended q 4 weeks to 28 weeks, q 2 weeks to 36 weeks, and then weekly until delivery.
5. See Chapter 12 (Preeclampsia).
6. See Chapter 53 (Prenatal diagnosis).
7. See Chapter 10 (Gestational diabetes mellitus)
8. See Chapter 24 (GBS)
9. See Chapter 55 (Screening for preterm birth)

High‐Risk Pregnancies

1. Antiphospholipid antibody syndrome (APLAS) is an autoimmune disease characterized by the presence in the maternal circulation of one or more autoantibodies against membrane phospholipid as well as one or more specific clinical syndromes. It is an acquired rather than an inherited condition. As such, it cannot explain a family history of venous thromboembolism (VTE). A significant family history of VTE should prompt testing to exclude inherited thrombophilias, including factor V Leiden mutation, prothrombin gene mutation, and protein S, protein C, and antithrombin deficiency.
2. The diagnosis of APLAS requires two distinct elements: (i) the correct clinical setting; and (ii) confirmatory serologic testing. Approximately 2–4% of healthy pregnant women will have circulating antiphospholipid antibodies in the absence of any clinical symptoms. As such, routine screening for these antibodies in all pregnant women is strongly discouraged.
3. Clinical manifestations of APLAS include: (i) recurrent pregnancy loss (defined as  ≥ 3 unexplained first‐trimester pregnancy losses or  ≥ 1 unexplained second‐trimester pregnancy loss); (ii) unexplained thrombosis (venous, arterial, cerebrovascular accident or myocardial infarction); and/or (iii) autoimmune thrombocytopenia (platelets <100,000/mm³). Recent consensus opinions suggest that such clinical conditions as unexplained intrauterine growth restriction (IUGR), massive placental abruption, and recurrent early‐onset severe pre‐eclampsia be included.
4. At least one of three serologic tests confirming the presence of circulating antiphospholipid antibodies (below) is required to make the diagnosis of APLAS. Moreover, the diagnosis requires the persistence of such antibodies as confirmed by two or more positive tests at least 12 weeks apart.
   • Lupus anticoagulant (LAC) is an unidentified antiphospholipid antibody (or antibodies) that causes prolongation of phospholipid‐dependent coagulation tests in vitro by binding to the prothrombin–activator complex. Examples of tests that can confirm the presence of LAC include the activated PTT test, dilute Russel viper venom test, kaolin clotting time, and recalcification time. In vivo, however, LAC causes thrombosis. LAC results are reported as present or absent (no titers are given). The term LAC is a misnomer: it is not specific to lupus (SLE) and it acts in vivo as a procoagulant and not an anticoagulant.
   • Antibodies against specific phospholipids as measured by enzyme‐linked immunosorbant assay (ELISA). These high‐avidity IgG antibodies have anticoagulant activity in vitro, but procoagulant activity in vivo. The most commonly used ELISA test is the anticardiolipin antibody (ACA). Cardiolipin is a negatively charged phospholipid isolated from ox heart. ACA ELISA is at best semi‐quantitative. Results have traditionally been reported as low, medium or high titers. More recently, standardization of the phospholipid extract has allowed for standard units to be developed (GPL units for IgG, MPL units for IgM). ACA IgM alone, IgA alone, and/or low‐positive IgG may be a nonspecific (incidental) finding since they are present in 2–4% of asymptomatic pregnant women. As such, moderate‐to‐high levels of ACA IgG (>40 GPL units) are required to make the diagnosis of APLAS.
   • The presence of anti‐β2‐glycoprotein I antibodies.
5. A number of additional antiphospholipid antibodies are described, including antiphosphatidylserine, antiphosphatidylethanolamine, antiphosphatidylcholine, anti‐Ro, and anti‐La, but these are not sufficient to make the diagnosis. A false‐positive test for syphilis (defined as a positive rapid plasma reagin (RPR) or Venereal Disease Research Laboratory (VDRL) test, but negative definitive test for syphilis) is another common finding in women with APLAS, but is nonspecific and is not sufficient to confirm the diagnosis. Antinuclear antibodies (ANA) are not antiphospholipid antibodies, and may suggest the diagnosis of SLE but not APLAS.
6. Treatment for APLAS depends on the clinical features:
   • For women with thrombosis (such as stroke or pulmonary embolism), therapeutic anticoagulation is indicated with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH) during pregnancy followed by oral anticoagulation (coumadin) postpartum because of a 5–15% risk of recurrence. In pregnancy, regular blood tests are required 4 hours after administration of the drug to ensure that anticoagulation is therapeutic: the PTT should be 1.5‐ to 2.5‐fold normal and anti‐Xa activity levels should be 0.6–1.0 U/mL. Side‐effects include hemorrhage, thrombocytopenia, and osteopenia and fractures. Such women may need lifelong treatment.
   • For women with recurrent pregnancy loss, treatment should include prophylactic UFH (5000–10,000 units sc bid) or LMWH (enoxaparin (Lovenox) 30–40 mg sc daily or dalteparin (Fragmin) 2500–5000 U sc daily) starting in the first trimester of pregnancy. Although prophylactic dosing does not change PTT, it will increase anti‐Xa activity to 0.1–0.2 U/mL. However, it is not necessary to follow serial anti‐Xa activity in such patients. The goal of this treatment is to prevent pregnancy loss and to prevent VTE, which is possible in women with APLAS in pregnancy even if they have not had a VTE in the past. Therefore, anticoagulation should be administered throughout pregnancy and typically for 6–12 weeks after delivery.
   • For women with autoimmune thrombocytopenia or a history of severe pre‐eclampsia, IUGR or placental abruption, the optimal treatment is unknown. Consider treating as for recurrent pregnancy loss. Postpartum anticoagulation is probably not necessary.