INTRODUCTION

High quality prenatal care has greatly contributed to improved outcomes for mothers and babies throughout the world. It is an opportunity to perform risk stratification in the hope of avoiding pregnancy complications for a variety of medical and obstetric conditions, including fetal growth restriction, red cell alloimmunization, depression, and HIV infection. In addition, it allows for early recognition and treatment of conditions such as pre-eclampsia, and reducing maternal and perinatal morbidity. Also, it facilitates risk stratification for pregnancies at risk for stillbirth, identifying cases that may benefit from iatrogenic late preterm and early term birth. Finally, prenatal care is an important opportunity to provide emotional support and health education for women and their families. This chapter reviews the basic tenets of prenatal care for both low- and high-resource settings with an emphasis on new information and controversial topics.

DETERMINATION OF GESTATIONAL AGE

An accurate estimation of gestational age is critical in early prenatal care and has been shown to improve obstetric outcomes. This information is vital in the timing of obstetric care, scheduling and interpretation of antenatal testing, determining appropriate fetal growth, and in the prevention of preterm and post-term births and their related morbidities. As soon as information on the first day of a woman’s last menstrual period (LMP) is known and/or the first accurate ultrasound examination is obtained, an estimated date of delivery (EDD) and gestational age should be determined, discussed with the patient, and clearly documented in the medical record. Changes in gestational dating should be reserved for rare circumstances and clearly documented in the medical record.

The American College of Obstetrics and Gynecology, the Institute of Ultrasound in Medicine, and the Society of Maternal and Fetal Medicine^1,2,3 make the following recommendations regarding determination of gestational age and EDD:

• Ultrasound measurement of the embryo or fetus in the first trimester (up to and including 13 + 6/7 weeks of gestation) is the most accurate method to establish or confirm gestational age;
• If pregnancy resulted from assisted reproductive technology (ART), the ART-derived gestational age should be used to assign the EDD. For instance, the EDD for a pregnancy resulting from in vitro fertilization should be established using the age of the embryo and the date of transfer;
• A pregnancy without an ultrasound examination that confirms or revives the EDD before 22 + 0/7 weeks of gestational age should be considered suboptimally dated.

While no perfect evidence exists to establish a single point cutoff in the difference between clinical and ultrasonographic EDD to prompt changes in a pregnancy’s EDD, it is imperative that a single standard approach be used between institutions in determination of gestational age. This standardized approach is a research and public health imperative because of the influence accurate dating has on vital statistics and research protocols. An expert review of all available evidence has established single point cutoffs that should be used universally (Table 1).⁴

It should be recognized that confirmatory ultrasonographic dating for every pregnancy is not readily available or feasible in all parts of the world. If ultrasound is unavailable, the first day of the patient’s LMP should be used in establishing an EDD. The EDD is calculated by adding 280 days to the first day of the patient’s last LMP. It is important to note that the use of this practice assumes that every woman has regular cycles occurring every 28 days with ovulation occurring on the 14th day of each menstrual cycle. It does not account for irregularity in cycle length or the timing of ovulation. It has been reported only up to 50% of women are able to recall their LMP when presenting for prenatal care making dating based on LMP difficult. Women without certain LMP dating should always be referred for ultrasonographic dating if possible.

PRENATAL CARE VISITS

Prenatal care should be initiated in the first trimester, ideally by 10 weeks' gestation. Early initiation of prenatal care is important to establish baseline weight, blood pressure, and laboratory abnormalities, to identify chronic disease and provide appropriate counseling to women who may be at increased risk of pregnancy complications. There are many different models for the provision of prenatal care. For example, care may be provided by single or multiple providers, and by physicians, midwives or other health care workers.  When care is given by multiple providers. it is crucial to use a medical record system that facilitates clear communication so that information is not lost or neglected. In addition, the use of checklists, etc. can ensure that important screening tests and other milestones are less likely to be missed due to human error.  

The initial prenatal visit

The first prenatal visit is used to gather a complete medical, obstetric and family history, physical examination, and laboratory studies to help identify pregnant women at increased risk of obstetric complications during pregnancy.

Return prenatal visits

The frequency of prenatal care visits should be individualized. A woman with an uncomplicated pregnancy is traditionally seen every 4 weeks for the first 28 weeks of gestation, every 2 weeks until 36 weeks of gestation, and then weekly until delivery. Routine visits typically include assessment of weight, blood pressure, uterine size or fundal height, and fetal heart rate. In the past, screening for proteinuria was advised recommended for each visit. More recent data indicate that targeted rather than universal screening is a more cost-effective approach.⁵ Recommendations for routine prenatal visits are summarized in Table 2.

Group prenatal care

Prenatal care has traditionally been provided in “one on one” or individual settings with providers and patients. However, it may also be conducted with groups of women. This approach, termed “group prenatal care”, has several potential benefits. These include decreased health care costs, decreased wait times, increased provider availability and increased time for patient education.¹¹ Group prenatal care also has the potential to improve outcomes in at risk groups with similar needs such as increased risk for preterm birth, diabetes, and adolescents. The model consistently leads to increased patient satisfaction, pregnancy knowledge, and breastfeeding.^11,12 Although there is no clear evidence of improved perinatal outcomes, group prenatal care is not associated with harm.¹²

PRENATAL LABORATORY STUDIES

At the beginning of every pregnancy a panel of certain laboratory tests should be obtained to identify conditions that may affect the mother or the fetus as pregnancy progresses. These tests should be performed at the first prenatal visit or when pregnancy viability is confirmed. As soon as results are available, they should be documented clearly in the medical record and, if appropriate, discussed with the patient. Abnormal results should prompt further investigation or treatment.

• Blood type (ABO) – this denotes the presence or absence of one, both, or neither A or B antigens on maternal erythrocytes. Thus, there is no “abnormal” result. Results are important if there is a need for an urgent blood transfusion during pregnancy or delivery.
• Blood type (RhD antigen) – this identifies women who are RhD antigen negative and may be at risk for developing red cell alloimmunization to the RhD antigen. Any women identified as D-negative and NOT sensitized (negative antibody screen) should receive 300 μg of anti-D immune globulin at 28–29 weeks of gestation and within 72 hours of delivery of a D-positive newborn. A single dose of 300 μg (Rhogam) is sufficient to suppress the immune response to 15 mL of D-positive red cells or 30 mL of D positive whole blood. An additional dose should be given at the time of ectopic pregnancy, threatened, spontaneous, or induced abortion, chorionic villus sampling (CVS) or amniocentesis, abdominal trauma, placental abruption, or unexplained vaginal bleeding during pregnancy. Higher doses may be needed in rare cases of severe fetal maternal hemorrhage at delivery. Dosing may also vary by RhD formulations. Finally, the routine administration of RhD immune globulin at 28–29 weeks' gestation is not performed in all centers throughout the world and cost-effectiveness is debated.¹³
• Antibody screen (indirect Coombs) – this determines if circulating antibodies are present in maternal serum, which bind red blood cells and may potentially cross the placenta and target fetal red blood cells resulting in hemolytic anemia of the fetus and newborn. A positive antibody screen is the result of exposure to foreign red blood cells either through previous pregnancy or a blood transfusion. Any positive test result should prompt assessment of the amount of antibody, termed a “titer”. If the antibody has the potential to cause fetal anemia, pregnancies with “critical titers” are at risk for hemolytic disease of the fetus and newborn. Common antibodies that may result in hemolytic disease of the fetus and newborn include RhD, Kell, Rhc, RhE, and Duffy. Anyone with a positive antibody screen for these antibodies should be referred to a specialist with expertise. Common antibodies that do not place pose fetal risk include Lewis, I, and P1 as these antibodies are IgM and cannot cross the placenta.
• Complete blood count counts a number of different cells in maternal blood including red blood cells, white blood cells, and platelets. A low red blood cell count indicates anemia, which is associated with increased maternal and perinatal morbidity.⁷ This is especially important in low-resource settings, and identification and treatment of anemia may improve maternal and child health.¹⁴ A high white blood cell count may help identify infections that require treatment, while a low platelet count (thrombocytopenia) identifies women who are at risk of bleeding. A CBC should be determined again in the third trimester of pregnancy.
• Rubella serology – this identifies antibodies made by the immune system to fight off the rubella virus. A critical titer must be reached for a woman to be considered immune that varies among laboratories. A woman who is not immune to the rubella virus may be at risk of acute rubella infection during pregnancy. In turn, this may lead to miscarriage, stillbirth, and congenital rubella syndrome, as well as deafness, cataracts, heart defects, intellectual disabilities, low birth weight, and skin rashes at birth.¹⁵ Unfortunately, women identified on their prenatal lab results to not be immune to rubella are not advised to receive the rubella vaccine during pregnancy, since it is a live attenuated vaccine. All women who are non-immune should be offered vaccination in the immediate postpartum period to prevent harmful effects of rubella in future pregnancies. This vaccination is safe with breastfeeding (prenatal care, ACFP updates).
• Hepatitis B surface antigen (HbsAg) – vertical transmission of hepatitis B occurs in millions of pregnancies each year. Fortunately, universal screening for hepatitis B infection has helped to reduce the rate of maternal–infant transmission of hepatitis B.⁸ Assay for HbsAg determines whether a woman has a current hepatitis B infection and is at risk of transmitting it to their child. An infant of a HBsAg positive mother should be treated with hepatitis B immune globulin at birth (as well as active hepatitis B vaccination). If the hepatitis B surface antigen is positive, the next step includes measuring baseline: (1) HBeAg; (2) anti-HBe; (3) hepatitis B virus (HBV) DNA level; and (4) aminotransferase levels. Referral to a specialist is appropriate.
• Serologic screen for syphilis (VDRL or RPR) – universal screening for syphilis is highly recommended as treatment with appropriate antibiotics can prevent adverse outcomes in the mother and fetus. If the initial screening test (VDRL or RPR) is positive, a second confirmatory treponemal test such as fluorescent treponemal antibody testing or the T pallidum passive particle agglutination assay should be performed. The specificity of serologic testing for syphilis is high if both a nontreponemal screen (VDRL or RPR) and a subsequent treponemal serologic test is positive. Repeat screening should be performed at 28–32 weeks' gestation and at delivery in women who are at high risk (having unprotected intercourse with more than one partner, area with high syphilis prevalence, illicit drug use, poverty, other sexually transmitted infection diagnosed in pregnancy).⁹
• HIV serology – as with hepatitis B, HIV infection may be transmitted from mother to baby. Vertical transmission can be significantly reduced with appropriate antiretroviral therapy.¹⁰ Accordingly, universal screening for HIV infection during pregnancy is advised. Since some women may avoid testing owing to perceived stigma, screening for HIV in pregnancy may be based on an “opt-out” policy. Women can be informed that they will be screened for HIV as part of a routine prenatal panel of tests performed in the first trimester. If a patient declines screening, it should be clearly documented in the medical record and patient reasons for declining the test should be explored. Screening is performed using an antibody–antigen test. If positive, this should be subsequently followed up with a nucleic acid-based HIV test. Repeat screening should be performed in the third trimester for women who live in an area of high prevalence, who are incarcerated, who develop symptoms of acute HIV infection, and those with risk-taking behavior including injection drug use, exchange of sex for money or drugs, more than one sex partner or a new partner, and those diagnosed with another sexually transmitted infection in the past year.
• Chlamydia – all women should be routinely screen for chlamydia during their first prenatal visit with culture or nucleic acid based screens. If positive, patient and partner should be treated. Repeat screening should be performed in the third trimester for all women less than 25 years old and those at high risk. Women with a previously treated positive result in pregnancy should be retested approximately 3–6 months from previous treatment as a “test of cure”.
• Gonorrhea – any women less than 25 years of age and any patient living in an area of high gonorrhea prevalence should be screened at their first prenatal visit. Similar to chlamydia, women with a previously treated positive result in pregnancy should be retested approximately 3–6 months from previous treatment as a test of cure.
• Hepatitis C – women at increased risk of hepatitis C should be screened for the disease at their first prenatal visit. Women at increased risk include injection drug users, anyone with a blood transfusion before July 1992, receipt of an unregulated tattoo, long-term hemodialysis, intranasal drug use, and other percutaneous exposures. Universal screening for hepatitis C infection during pregnancy is advocated by some.¹⁶
• Tuberculosis (TB) – all pregnant women who are at high risk of tuberculosis should be screened at their first prenatal visit with either the purified protein derivate (PPD) or interferon-gamma release assay (IGRA). Women at high risk include those with exposure history to TB, any patient living in an endemic country, immunosuppressed patients, any patient living or working in correctional institutions, homeless facilities, or healthcare facilities, and any foreign-born patient who has emigrated from endemic countries within the past 5 years. If a test result is positive, an evaluation for active disease should be performed with exploration of symptoms and chest radiograph. If an individual is asymptomatic and does not have active disease, treatment with isoniazid and pyridoxine should be initiated in the second trimester of pregnancy for latent TB. Any pregnant women with concern for active TB should be referred to an infectious disease specialist.
• Urine culture – universal screening for asymptomatic bacturia is advised. In non-pregnant individuals it has not been proven efficacious to treat asymptomatic bacturia. However, asymptomatic bacturia increases the risk for pyelonephritis during pregnancy. Accordingly, screening and treatment in cases of positive culture is recommended. Test of cure should be accomplished to be certain that the infection has been adequately treated. If there is a positive culture for group B streptococcus (GBS), the patient should be considered to be colonized with GBS and she should receive intrapartum antibiotics.

GENETIC SCREENING OR TESTING

In places with adequate resources and availability, it is the responsibility of an obstetric physician to counsel a pregnant woman on her options for genetic screening or to refer a patient to a certified genetic counselor. Options for genetic testing are vast and an obstetric care provider should be knowledgeable about the options available to their patients. The decision to pursue genetic screening should be an informed patient choice with shared decision-making based on patient circumstances and values. Ideally, this discussion or referral to a genetic counselor should occur at the first prenatal visit.

With ever-increasing options for genetic screening it has become more difficult for an obstetric provider to stay up to date on the best screening and diagnostic tests for their patients. One study noted that general obstetricians missed relevant genetic information in over half of cases, with approximately 40% of that information leading to a subsequent change in clinic care and genetic testing offered.¹⁷ If available, it is advisable to refer any patient who desires genetic screening for counseling.

Aneuploidy

The most common prenatal genetic screening is assessment of a woman’s risk for carrying a fetus with one or more of the common fetal aneuploidies. Aneuploidy is defined as having one or more extra or missing chromosomes which often results in a nonviable pregnancy and in the case of surviving newborn, birth defects, mild to severe intellectual disability, and a shorten lifespan. The incidence of fetal aneuploidy increases with increasing maternal age and is not related to race or ethnicity. The most common inherited form of intellectual disability is Down syndrome (trisomy 21) occurring in 1 in 800 live births. Other relatively common aneuploidies include trisomy 13 and 18, Klinefelter syndrome (47,XXY), and Turner syndrome (45,X).

There are a wide variety of options for testing for fetal aneuploidy each offering varying levels of information and accuracy. Each test has its advantages and disadvantages discussed in Table 3 and no one test is always superior to others. The choice of screening test is affected by many factors including a patient’s gestational age, their desire for more information prior to delivery, previous obstetric history, family history, cost of testing, availability, and personal values and concerns. It is important to note that aneuploidy screening is a screening rather than a diagnostic test. Women who screen positive are at increased risk of having a fetus with an aneuploidy and should be counseled regarding options for diagnostic testing. Women that screen negative are at lower post-test probability of fetal aneuploidy. Simultaneous testing with multiple screening modalities is not cost-effective and should not be performed.

First trimester screen

The first trimester screen is available between 10 + 0/7 weeks and 13 + 6/7 weeks' gestation. This test measures nuchal translucency and two maternal serum biomarkers (total human chorionic gonadotropin (hCG) and pregnancy associated plasma protein A (PAPP-A)) in combination with maternal characteristics to establish risk. Nuchal translucency refers to measurement of the fluid-filled space on the dorsal aspect of the fetal neck. An enlarged nuchal translucency of >99% for crown–rump length or approximately 3.0 mm is independently associated with fetal aneuploidy and structural malformations, especially cardiac. This measurement must be precise to ensure sensitivity and therefore must be performed by a credentialed sonographer.

Quadruple screen

The quadruple (“quad”) screen can be performed between 15 + 0/7 weeks and 22 + 6/7 weeks of gestation. The best time to perform this test is between 16 and 18 weeks’ gestation as this optimizes screening for neural tube defects in addition to aneuploidy. The quad screen involves measurement of four components of maternal serum: (1) hCG, (2) alpha fetoprotein (AFP), (3) dimeric inhibin A, and (4) unconjugated estriol. These values are taken in combination with maternal factors such as age and weight to calculate a risk estimate for aneuploidy. This can be used in combination with a first trimester nuchal translucency measurement this is known as the integrated screen.

Cell free DNA

Next-generation sequencing of fetal cell-free (cf) DNA in maternal circulation is the aneuploidy screening option with the highest sensitivity and specificity. The primary source of fetal cfDNA in the maternal circulation is thought to be from the apoptosis of placental cells. Fetal cfDNA can be performed at >10 weeks' gestation. The test is quite attractive since it has excellent performance characteristics with no medical risk. However, it is expensive and not universally available. The pros and cons of various screening tests for aneuploidy are depicted in Table 3.

Carrier screening

Screening should be offered for a variety of genetic mutations that are not identified by chromosome analysis. Examples include autosomal recessive single gene mutations, wherein parents may be asymptomatic heterozygous carries. The value and cost-effectiveness of screening for individual conditions varies considerably among populations and approaches may be individualized. For example, the rate of conditions such as cystic fibrosis, Tay Sachs disease, and thalasemias differ substantially by race and ethnicity. Other conditions may only be identified by a careful family history such as screening for fragile X permutations in cases of families with unexplained intellectual disability.

IMMUNIZATIONS IN PREGNANCY

Routine assessment of pregnant patients’ vaccination status should be performed at the first prenatal visit.¹⁹ In turn, appropriate immunizations should be provided as outlined in Table 4.¹⁹ Immunizations that may be warranted during pregnancy include pneumococcal, meningococcal conjugate and meningococcal serogroup B, hepatitis A and B, and human papillomavirus (HPV) vaccines. Vaccinations currently recommended in all pregnancies are inactivated influenza and Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis). It is safe for the inactivated influenza and Tdap vaccines to be administered concomitantly.

Pregnant women should receive any age-appropriate, inactivated influenza vaccine during their pregnancy, and the vaccine may be administered during any trimester. Although imperfect, the efficacy of seasonal influenza vaccines in pregnant women is approximately the same as that in the general population and is the primary method of prevention from seasonal influenza. Antepartum vaccination provides neonatal and postnatal protection via transplacental transmission of antibodies, because the influenza vaccine is ineffective in infants younger than 6 months. In addition, some data suggest that maternal illness is relatively more severe with influenza infection during pregnancy than in non-pregnant individuals.²⁰ It should be noted that live attenuated influenza vaccination should be avoided in pregnant women. Thimerosal, a preservative found in inactivated influenza vaccines has not been shown to have adverse fetal effects on children.

Tdap vaccine is the second vaccination recommended during every pregnancy, even if the patient has been previously vaccinated. The goal of vaccination is to decrease the risk of severe postnatal infection in the infant. Thus, Tdap vaccine should be administered at 27–36 weeks of gestation – the earlier within the window, the better (this optimizes transplacental transmission of antibodies). Nonetheless, the Tdap vaccine can be administered any time point during the pregnancy if not given in the ideal window. Additionally, a mother should be vaccinated postpartum if not vaccinated during the pregnancy. The Tdap vaccination should be administered with each subsequent pregnancy, acting as a booster to the maternal immune response and maximizing passive antibody transmission.

Live vaccination of an antepartum patient poses a theoretical risk to the fetus and should be avoided in most cases. This is most frequently encountered in the setting of the measles-mumps-rubella and varicella vaccines. If non-immune, first dose MMR and varicella vaccines should be provided during the postpartum period. Despite theoretical concerns, fetal harm from inadvertent vaccination during human pregnancy has not been demonstrated. Thus, women should be reassured under such circumstances.

EDUCATION

Orientation to maternity care

A provider should provide education at all new obstetric visits about the logistics and structure of their maternity clinic. Women should be informed on how to reach their provider/clinic after business hours in case of emergency as well as where to go in the event of an obstetric emergency. Women should be educated on the symptoms that should prompt obstetric evaluation outside of routine obstetric care. These symptoms include but are not limited to vaginal bleeding, leakage of fluid from the vagina, fever, pain, acute shortness of breath, calf or leg pain, headache not relieved by usual measures, dysuria, pruritis, uterine contractions, decreased fetal activity, or fainting or dizziness.

Prenatal vitamins

A standard prenatal multivitamin with iron and folic acid satisfies the daily vitamin and mineral requirement of most pregnancy women. It should be recommended that all pregnant women take one prenatal vitamin daily. The multivitamin should contain 30 mg/day of iron to reduce pregnancy-associated anemia and 0.4 to 0.8 mg of folic acid to reduce open neural tube defects. Ideally, the folic acid would be initiated prior to and through conception and early pregnancy. Women with iron deficiency anemia should receive additional iron supplementation.

Weight gain

A women’s body mass index (BMI) should be determined at their initial prenatal visit. Appropriate weight gain in pregnancy is based on pre-pregnancy BMI, which is calculated by taking weight (kg)/height (m²). The Institute of Medicine (IOM) has established guidelines for maternal weight gain based on pre-pregnancy BMI.²¹ These recommendations are as follows:

• Singleton pregnancy
  • BMI <18.5 kg/m² (underweight) – weight gain 28–40 lb (12.5–18.0 kg)
  • BMI 18.5–24.9 kg/m² (normal weight) – weight gain 25–35 lb (11.5–16.0 kg)
  • BMI 25.0–29.9 kg/m² (overweight) – weight gain 15–25 lb (7.0–11.5 kg)
  • BMI ≥30.0 kg/m² (obese) – weight gain 11–20 lb (5–9.0 kg)
• Twin pregnancy
  • BMI <18.5 kg/m² (underweight) – no recommendation due to insufficient data
  • BMI 18.5–24.9 kg/m² (normal weight) – weight gain 37–54 lb (16.8–24.5 kg)
  • BMI 25.0–29.9 kg/m² (overweight) – weight gain 31–50 lb (14.1–22.7 kg)
  • BMI ≥30.0 kg/m² (obese) – weight gain 25–42 lb (11.4–19.1 kg)

Every woman should be counseled on appropriate weight gain, diet, and exercise at their initial prenatal visit and reminded throughout their pregnancy. Ideally, a woman’s BMI is normal prior to pregnancy; however, rates of obesity are increasing.

Excessive weight gain in pregnancy has been associated with an increased risk of macrosomia and large for gestational age (LGA) infants, cesarean delivery, pregnancy-related hypertension, and gestational diabetes.²² Following pregnancy, women who experience weight gain above IOM recommendations are at increased risk for obesity, future cardiovascular disease and diabetes. Weight gain below IOM recommendations increases patient risk for a small for gestational age (SGA) infant and preterm birth. It is important to monitor weight gain routinely at each prenatal visit and discuss abnormal weight gain with the patient.

Nutrition

Maternal and fetal outcomes are affected by maternal nutrition during pregnancy. All women should receive counseling on recommendations for a well-balanced diet throughout pregnancy. Pregnant women who are at high risk of a nutritional deficiency or excessive weight gain in pregnancy should be referred to a nutritionist or dietitian early in pregnancy.

The number of additional calories required for a typical pregnancy is small. Pregnant women of normal BMI with a singleton pregnancy need to increase daily caloric intake by 0 kcal/day in the first trimester, 350 kcal/day in the second trimester, and 450 kcal/day in the third trimester. These caloric increases are highly dependent on physical activity, age, and BMI and recommendations should be individualized.

In general, a woman should focus on a well-rounded diet in pregnancy. They should eat plenty of fruits, vegetables, whole grains, low-fat dairy, and proteins. Women should avoid foods that are high in added sugar and solid fats. To obtain a caloric intact of between 2200 and 2900 kcal/day in the second and third trimester women a generic recommendation for each food group is as follows:

• Fruits – 2–2.5 cups
• Vegetables – 3–3.5 cups
• Grains – 6–10 ounces
• Protein – 6–7 ounces
• Dairy – 3 cups

Women should limit or avoid certain food groups in pregnancy due to their potentially toxic effects. These include:

• Undercooked meats due to risk of toxoplasmosis, Listeria moncytogenes and brucellosis;
• Unpasteurized dairy products due to risk of Listeria monocytogenes and brucellosis;
• Unwashed fruits/vegetables due to risk of toxoplasmosis;
• Some types of fish. Pregnant women should avoid eating shark, king mackerel, marlin, orange roughy, tilefish, and bigeye tuna. These fish may be contaminated with environmental pollutants specifically methylmercury. Exposure to methylmercury may (in theory) cause severe fetal central nervous system damage. Eating 8–12 oz of fish other than those listed above per week is considered safe.
• High caffeine intake: In 2010, ACOG released a committee opinion that recommends limiting caffeine consumption to less than 200 mg/day in pregnancy.²³ Eight ounces of brewed coffee contains on average 133 mg of caffeine. A dose response relationship of caffeine intake to adverse pregnancy affects has been noted in several studies. Adverse effects associated with high caffeine intake include low birth weight and risk of pregnancy loss, although data are mixed and any risks are low.²⁴

Exercise

Women with uncomplicated pregnancies should be encouraged to exercise as a part of a healthy lifestyle before, after, and during pregnancy. Although evidence is limited, some benefit to pregnancy outcomes has been shown without evidence of harm when exercise is not contraindicated.²⁵ Observational studies of women who exercise in pregnancy show decreased risk of musculoskeletal discomfort, urinary incontinence, gestational diabetes, cesarean and operative vaginal delivery, pre-eclampsia, and excessive weight gain as well as a shorter postpartum recovery time.²⁵ These benefits are in addition to the same long-term medical and psychological benefits of exercise found in non-pregnant individuals. The US Department of Health and Human Services issued guidelines encouraging 150 minutes of moderate intensity aerobic activity (e.g. brisk walking) per week for pregnant women. Women who engage in high intensity physical activity may continue throughout pregnancy unless there is a specific contraindication. Exercise should be discontinued if women experience any of the following warning signs: vaginal bleeding, regular painful contractions, amniotic fluid leakage, dyspnea before exertion, dizziness, headache, chest pain, calf pain or swelling, of muscle weakness affecting balance. It is recommended that women who experience these symptoms seek medical advice prior to restarting their exercise regimen.

The type of exercise selected should be based on individual preference; however, high impact physical activity that places a woman at risk of abdominal trauma and subsequent placenta abruption should be avoided. Activities to consider avoiding include contact sports, downhill skiing, water skiing, surfing, horseback riding, and sky-diving. Women are also advised to avoid hot yoga and hot Pilates due to the risk of hyperthermia.

Nausea and vomiting

Nausea with or without vomiting affects up to 90% of pregnant women and may be considered part of the normal physiology of the first trimester. The pathogenesis of nausea and vomiting of pregnancy is unknown. Risks factors for nausea and vomiting of pregnancy include previous nausea with estrogen-based medications, previous nausea with pregnancy, history of motion sickness, and a history of migraines. Taking multivitamins early in pregnancy can reduce the risk of vomiting requiring medical attention.

First-line therapy for the treatment of nausea and vomiting in pregnancy includes avoidance of triggers and dietary changes. Women with nausea should eat before or as soon as they feel hungry, as an empty stomach may aggravate nausea. Woman should determine what foods they tolerate best and try to eat those foods. Sometimes dietary manipulations such as eliminating coffee and spicy, odorous, high fat, acidic foods and adding more protein dominant, salty, low fat, bland foods may help reduce nausea and vomiting. Additionally, foods with ginger may improve nausea associated with pregnancy. If these first-line changes do not successfully manage a patient’s nausea and vomiting, it can be recommended that women take pyridoxine, vitamin B6, with or without doxylamine. The recommended dose of pyridoxine is 10–25 mg orally every 6–8 hours. Combination tablets of doxylamine-pyridoxine are available, but may be costly to patients. If doxylamine-pyridoxine is ineffective, other drugs such as diphenhydramine, metoclopramide, promethazine, or ondansetron may be added in a step-wise fashion.

Hyperemesis gravidarum, a severe form of pregnancy-associated nausea and vomiting associated with hypovolemia and weight loss occurs in less than 2% of pregnancies. Women with hyperemesis gravidarum should have a medical evaluation. Hospital admission is appropriate for individuals who have persistent vomiting despite replacement fluids and electrolytes and intravenous antiemetic therapy.

Oral health

Dental care should not be deferred because of pregnancy. Dental radiographs and procedures such as local anesthesia, dental extraction, root canals, and treatment of caries are not harmful to the fetus. Pregnant patients should be made aware that their gums bleed more easily in pregnancy. Physiologic changes during pregnancy may result in noticeable changes in the oral cavity including gingivitis, benign oral gingival lesions, tooth mobility, tooth erosion, dental caries, and periodontitis. Periodontal disease may be associated with an increased risk of preterm delivery and therefore women should be reminded to reinforce good oral health habits before, during, and after pregnancy.

Teratogens

Major birth defects occur in 2–4% of pregnancies in the general population. Women should be counseled that relatively few agents are known to cause malformations in pregnancy. The Organization of Teratology Information Specialists provides information on teratology issues and exposures in pregnancy (www.otispregnancy.org). The use of known or potentially teratogenic medications should ideally be stopped prior to conceiving. These medications include warfarin, valproic acid, carbamazepine, isotretinoin, and angiotensive-converting enzyme inhibitors. The use of non-steroidal anti-inflammatory agents (NSAIDS) other than low dose aspirin for more than 48 hours should also be avoided in pregnancy. Several antibiotics should also be avoided in pregnancy. Aminoglycosides carry a risk of fetal ototoxcity and nephrotoxicity, tetracyclines may cause adverse effects on fetal bone and teeth, and fluroquinolones are best avoided during pregnancy and lactation due to their toxic effect on developing cartilage. In general, women should consult with their health care provider before using prescription and nonprescription medications or herbal remedies. Physicians may also refer to the CDC’s web page on medication use during pregnancy at www.cdc.gov/pregnancy/meds/treatingfortwo/index.html for information on medication safety.

Pregnant women commonly express concern for the teratogenic potential of diagnostic imaging during pregnancy. According to the American College of Radiology, no single diagnostic X-ray procedure results in radiation exposure to a degree that would threaten the health of a fetus at any gestational age. Concern about radiation exposure during pregnancy should not prevent medically indicated diagnostic X-ray studies. Similarly, the use of computed tomography (CT) should not be withheld if clinically indicated, but a thorough discussion of the risks and benefits should take place. Exposure to radiation from a CT varies based on the number of imaging sections necessary. When a CT is indicated the minimal dose of radiation should be used. MRI should be considered as a safer alternative to CT imaging during pregnancy in cases in which they are equivalent for the diagnosis in question. IV iodinated contrast media should only be used if absolutely required due the potential adverse effects of free iodide on the fetal thyroid gland.

Elevation of core body temperature may be associated with fetal anomalies such a neural tube defects. Thus, it is recommended that pregnant women remain in saunas for no more than 15 minutes or hot tubs for no more than 10 minutes to avoid hyperthermia.

Mental health

Mental health disorders such as depression and anxiety are incredibly common in reproductive-aged women and, thus, during pregnancy. Moreover, they are often exacerbated by pregnancy and postpartum. Accordingly, universal screening is advised. Several screens are effective and typically take fewer than 10 minutes to complete. Examples include the Edinburgh Postnatal Depression Scale, Postpartum Depression Screening Scale, and Patient Health Questionnaire-9.²⁶ Women with positive screens or known depression or anxiety should be referred for counseling about management options.

Tobacco use

Tobacco use is still common during pregnancy in many places despite clear evidence of adverse effects on health. Smoking is associated with an increased risk for perinatal mortality and morbidity associated with conditions such as all types of perinatal loss, fetal growth restriction, preterm premature rupture of membranes, placenta previa, and abruption. It also increases the odds of childhood problems including asthma, obesity, and colic.²⁷ Exposure to second-hand smoke, also known as 'passive smoking' from any type of smoke (e.g. shisha/hookah/nargile, cigarettes, cigars, bidis, marijuana leaf), and the use of smokeless tobacco and e-cigarettes also pose serious health risks to pregnant women and children.²⁸ Smoking cessation or reduction during pregnancy should be encouraged since pregnant women may be relatively more motivated due to concerns for the health of their baby. Psychosocial interventions (counselling, feedback and incentives) for women who smoke during pregnancy reduces smoking rates and improves perinatal outcomes..²⁹ The safety and efficacy of nicotine replacement therapy during pregnancy is uncertain.³⁰ However, it is not contraindicated and may be used after careful counseling with motivated patients.³¹

Substance use disorder

Screening for substance use and substance use disorders also is appropriate. 

Pregnant women should be advised to avoid alcohol since it can cause birth defects, intellectual disability, and central nervous system abnormalities. There is no known “safe” threshold and all alcohol is contraindicated. Small amounts of alcohol should not be considered a reason for pregnancy termination. However, women who are drinking during pregnancy should be advised to stop.

Many other drugs may be abused and some are potentially addictive. Narcotic (illicit and prescribed) use disorder is increasingly common and is associated with many perinatal risks including neonatal abstinence syndrome. If possible, individuals with substance use disorder should be cared for in centers with appropriate multidisciplinary expertise. Marijuana is increasingly used during pregnancy owing to increased legalization in many locations. It is often used to treat nausea and vomiting of pregnancy and there is a perception that it is natural and safe. Although data are mixed, some studies suggest increased risks including stillbirth, preterm birth, fetal growth restriction and neonatal intensive care admission.^31,32 Thus, women should be advised to refrain from using marijuana during pregnancy.

Intimate partner violence

It also is important to screen for intimate partner violence during pregnancy. This affects millions of women throughout the world each year and may increase during pregnancy. This may involve physical, verbal, psychological and/or sexual abuse. Screening is best accomplished via direct questioning, and may require repeated queries in a private setting. It is important to be mindful of safety when performing such screening. Providers should learn about local resources to help women who are victims of intimate partner violence.

Fetal movement

Women should be advised to report decreased perception of fetal movement, especially late in pregnancy. They should be reassured that although this symptom may precede fetal death, it also is common in normal pregnancies. Nonetheless, they should be advised that decreases in fetal movement should prompt medical evaluation. The utility of widespread formal assessment of fetal movement is uncertain. The AFFIRM trial was a large, stepped wedge cluster randomized trial evaluating a reduced fetal movement care package.³³  The intervention was associated with a non-significant reduction in stillbirth from 4.40 per 1000 to 4.06 per 1000 (aOR 0.90, 95% CI 0.75–1.07; P = 0.23).³³ Fetal kick counting is often recommended; for example women are sometimes advised to count 10 movements in 2 hours. If they cannot perceive 10 movements, then they are advised to seek medical attention. However, this strategy may lead to anxiety and cost and is of unproven efficacy.

Sleep position

The optimal sleep position during pregnancy remains uncertain, but it is generally accepted that women should be advised to sleep on their side rather than on their back. Lying supine, especially later in pregnancy may result in supine hypertensive syndrome. This is characterized by severe hypotension, increased heart rate and symptoms such as dizziness, nausea, and lightheadedness, which usually compel the woman to change position. It is thought that this is associated with a decrease in blood flow to the baby and an increased risk for related conditions such as stillbirth, fetal growth restriction and gestational hypertensive disorders. Indeed, several case–control studies noted an increased risk for stillbirth and small for gestational age neonate when mothers recalled going to sleep in the supine position.^34,35

However, a prospective cohort study that objectively measured sleep position found no association between supine sleep and adverse pregnancy outcomes including stillbirth and small for gestational age neonate.³⁶ The latter study had limited power to assess stillbirth and did not assess sleep position during the last 2 months of pregnancy, when risk may be highest.³⁶ 

Breastfeeding

The advantages of breastfeeding should be discussed during antenatal visits. These include nutritional advantages as well as a decreased risk for many acute and chronic illnesses. There also are maternal benefits. Raising this topic prior to delivery allows women adequate time for education and decision making prior to the stressful immediate postpartum period.

Contraception

Ideally, postpartum contraception should be discussed during antenatal care. This allows for adequate time to consider the relative benefits and risks of various methods and to obtain adequate resources to obtain contraception. In addition, it is an opportunity to review optimal inter-pregnancy intervals.

GROUP B STREPTOCOCCUS

Group B streptococcus (GBS) remains an important cause of serious newborn infection. The infant usually acquires the bacteria during labor or after rupture of membranes in women who have colonization of the genitourinary or gastrointestinal tracts. Approximately 20% of women are colonized but rates vary by population. Vertical transmission of GBS occurs in about half of cases in colonized women; 1–2% of these infants develop serious early onset neonatal sepsis. Intrapartum antibiotics in women with GBS colonization can significantly decrease the risk of neonatal GBS infection.³⁷ Thus, it is advisable to perform universal screening for GBS colonization with vaginal-rectal culture obtained between 36 + 0/7 and 37 + 6/7 weeks' gestation. Women with positive cultures should receive appropriate intrapartum antibiotics³⁷ except in cases of cesarean birth prior to labor and with intact membranes. Instead of universal screening, some centers only screen pregnancies with risk factors for neonatal GBS sepsis such as preterm birth. The optimal approach to GBS screening remains uncertain.                

ULTRASOUND AND FETAL SURVEILLANCE

In centers with availability, routine antenatal ultrasound is recommended. Perhaps the most important benefit of obstetric ultrasound is accurate gestational dating (see above). The frequency and timing of routine ultrasounds vary throughout the world. First trimester ultrasound may be useful in cases of uncertain gestational age, uncertain viability, suspected ectopic pregnancy, vaginal bleeding, possible multiple gestations, aneuploidy screening with nuchal translucency, and suspected molar pregnancy. If a single screening sonogram is performed, the optimal timing is between 18 and 20 weeks’ gestation. This allows for reasonably good confirmation of gestational dating, evaluation of the placenta and assessment of fetal anatomy. Follow-up sonograms are indicated for numerous medical and obstetric conditions such as twins, chromic hypertension, and diabetes. They also are appropriate for suspected fetal growth abnormalities, suspected amniotic fluid abnormalities, vaginal bleeding, fetal abnormalities, etc. Depending upon the problem, referral to a specialty center with expertise and experience in obstetric sonogram may be appropriate.

Numerous pregnancies benefit from antenatal testing such as non-stress tests (NST), biophysical profiles (BPP) and Doppler velocimetry. For the most part, these tests assess placental function and serve as early markers of placental insufficiency. In turn, they allow for interventions such as medically indicated preterm birth in hopes of avoiding worse problems such as stillbirth or fetal or neonatal brain injury. Examples of conditions warranting antenatal testing include chronic hypertension, pregestational diabetes, systemic lupus erythematosus, small for gestational age fetus, postdates, pre-eclampsia, and decreased fetal movement.

SELECTED COMPLICATIONS OF PREGNANCY

Iron deficiency anemia

Approximately 40% of all pregnant woman globally have anemia. Blood volume expands approximately 50% and red blood cell mass expands by approximately 25% during pregnancy leading to a significant increase in a body’s need for iron. The greater the expansion of plasma, the higher the iron requirement. If an adequate iron supply is not present it is reflected by decreases in hemoglobin and hematocrit levels. Measurements of hemoglobin and hematocrit are the primary screening tests for identifying iron deficiency. Anemia in pregnancy is defined as Hgb (g/dL) and HCT (percentage) levels below 11 g/dL and 33%, respectively, in the first trimester; 10.5 g/dL and 32%, respectively, in the second trimester; and 11 g/dL and 33%, respectively in the third trimester. All pregnant women should undergo screening at their first prenatal visit and between 24 and 28 weeks' gestation for iron deficiency anemia. If found to have iron deficiency anemia of pregnancy, iron supplementation in addition to prenatal vitamins should be recommended to meet the iron requirements of pregnancy. The most common formula of oral iron prescribed is ferrous sulfate at a dose equivalent to 60 mg of elemental iron daily. Dosing may be spaced to every other day to reduce gastrointestinal side-effects.

Iron supplementation results in an increase in hemoglobin level in approximately 2 weeks. Hemoglobin levels should be rechecked 2–3 weeks following initiation of therapy. If an increase in hemoglobin level is not seen, investigation into alternatives causes of anemia should be performed.

Iron deficiency anemia during pregnancy has been associated with an increased risk of low birth weight, preterm delivery, and perinatal mortality.³⁸ In severe cases (Hgb <6 g/dL) a maternal blood transfusion is recommended as this level of anemia may lead to fetal compromise: abnormal fetal heart rate patterns, reduced amniotic fluid volume, fetal cerebral vasodilation, and even fetal death.

Gestational diabetes

Gestational diabetes mellitus (GDM) is a major cause of perinatal morbidity that occurs when carbohydrate intolerance develops during pregnancy. Rates vary among populations and based on definitions, but prevalence is increasing owing to increased maternal age and obesity. Maternal risks associated with GDM include pre-eclampsia, cesarean delivery, and increased odds of developing type 2 diabetes later in life. For example, up to 70% of women with GDM will eventually develop type 2 diabetes.³⁹ Fetal and neonatal risks include macrosomia, birth trauma, shoulder dystocia, neonatal hypoglycemia, hyperbilrubinemia, and stillbirth. There also is an increased risk of subsequent obesity and diabetes in the offspring.

Maternal and fetal risks can be reduced with appropriate medical care and glycemic control. Accordingly, screening is advised between 24 and 28 weeks' gestation. Universal screening is advised since risk-based screening will miss a substantial proportion of women with GDM.⁴⁰ In addition, it is worthwhile to screen for undiagnosed pregestational diabetes in women at high risk at the initiation of prenatal care. The optimal screening method or population to screen is uncertain.

The optimal screening test for GDM is controversial. Many organizations promote a one-step approach using a 75 gram 2 hour oral glucose tolerance test.⁴¹ Blood sugars are assessed after fasting, and then at 1 and 2 hours after the glucose load. Any single abnormal value (fasting value >92 mg/dL; 1 hour value >180 mg/dL; or 2 hour value >152 mg/dL) is sufficient for a diagnosis of GDM. These thresholds are based on data from the Hyperglycemia and Adverse Pregnancy Outcome study (HAPO) study and are endorsed by the International Association of Diabetes and Pregnancy Study Group (IADPSG).^41,42 A two-step approach is also commonly used, especially in the United States. This typically involves the administration of a 50 gram glucose load (no fasting required) and assessing blood glucose 1 hour later. If a woman has an abnormal screen on the 1 hour test, a 3 hour glucose tolerance test is performed. This consists of obtaining a fasting glucose, and then assessment of blood glucose 1, 2 and 3 hours after a 100 gram glucose load. The optimal thresholds for defining abnormal tests are uncertain. The threshold for a positive 1 hour screen varies from 130 to 140 mg/dL, with lower values yielding higher sensitivity and lower specificity. Thresholds for the 3 hour glucose tolerance test also vary. The most commonly used are Carpenter Coustan or National Diabetes Group criteria (Table 5).⁴³ The one step screen leads to a larger proportion of women being diagnosed with GDM compared to the two step screen. Estimates are as high as 2–3 fold more with the additional women having relatively milder glucose intolerance. Although they are at increased risk for macrosomia, they are at lower risk of more serious adverse outcomes such as stillbirth. Accordingly, the relative costs and benefits of each screening approach remains a matter of debate.⁴³

Women with a diagnosis of GDM should undergo nutritional counseling and learn how to monitor blood sugar levels. A reasonable approach is to assess fasting blood sugars and postprandial blood sugars after each meal each day. Other regimens also may be appropriate and there are no data to guide the optimal frequency of testing. Optimal glycemic targets also have not been identified. However, authorities recommend that fasting blood sugars are <95 mg/dL and postprandial blood sugars <140 mg/dl (1 hour) or <120 mg/dL (2 hours).⁴⁴

Treatment of GDM reduces the risk of maternal and fetal adverse outcomes.^45,46 A discussion of the pharmacologic and obstetric management of GDM is beyond the scope of this chapter. However, detailed resources are available.⁴³

SPONTANEOUS PRETERM BIRTH PREVENTION

Spontaneous preterm birth is a leading cause of neonatal morbidity and mortality. Although data are inconsistent, antenatal progesterone may reduce the risk of preterm birth in at risk pregnancies.^47,48,49 Also, treatment appears to be safe and is well tolerated. Thus, women with prior spontaneous preterm birth should be offered intramuscular 17-alpha-hydroxyprogesterone-caproate (17-OHP). Treatment is 250 μg weekly initiated between 16 and 20 weeks' gestation and continued until 37 weeks' gestation or delivery. This approach is generally accepted,^47,48 although data are mixed.⁵⁰ Women with a short cervix (<2.5 cm) less than 24 weeks' gestation should be offered vaginal progesterone. This is typically initiated at the time of ascertainment of the short cervix and is continued through 37 weeks or delivery. The optimal protocol to screen for short cervix is uncertain. Some centers advocate universal transvaginal sonogram to assess the cervix at mid-gestation, while others use a transabdominal screen and reserve transvaginal sonogram for cervix <3.0 cm on transabdominal scan.⁵¹

Some women with prior spontaneous preterm birth may benefit from cerclage placement. Indications for cerclage are beyond the scope of this chapter. However, women at risk for preterm birth should be referred to a specialist with expertise.

PRE-ECLAMPSIA PREVENTION

Low-dose aspirin can reduce the risk of pre-eclampsia and other gestational hypertensive disorders.^52,53,54 The effect is modest in low-risk women and is somewhat higher in women at highest risk for pre-eclampsia.⁵² The optimal time for the initiation of aspirin and the optimal dose of aspirin is uncertain, but some studies note increased effect if initiated prior to 16 weeks' gestation. The typical low-dose of aspirin in the United States is 81 mg per day and in Europe is 100 mg/day. Optimal dosing may be higher, especially in obese women. However, safety data are based on doses less than 150 mg/day. Importantly, full dose aspirin and other high dose NSAIDS have been associated with adverse fetal effects. In addition to reduced risk of pre-eclampsia, low-dose aspirin reduces the risk of fetal growth restriction, perinatal death, and preterm birth.⁵² However, for the most part, these have been secondary outcomes in randomized trials.

The population that should be treated with low-dose aspirin also remains uncertain. In the past it was recommended that aspirin should be used in a small percentage of women with prior severe pre-eclampsia. However, more recently, the US Preventive Task Force advised use in a larger percentage of women with modestly elevated risk.⁵⁵ These expanded guidelines have been endorsed by ACOG⁵⁶ with risk factors including things like obesity, chronic hypertension, and multiple gestations. Others have argued that it may be most cost-effective to treat all pregnant women with low-dose aspirin.⁵⁷

PRACTICE RECOMMENDATIONS