It is advantageous to diagnose pregnancy as promptly as possible when a sexually active woman misses a menstrual period or has symptoms suggestive of pregnancy. In the event of a desired pregnancy, prenatal care can begin early, and potentially harmful medications and activities such as drug and alcohol use, smoking, and occupational chemical exposure can be halted. In the event of an unwanted pregnancy, counseling about adoption or termination of the pregnancy can be provided at an early stage.
All urine or blood pregnancy tests rely on the detection of human chorionic gonadotropin (hCG) produced by the placenta. hCG levels increase shortly after implantation, approximately double every 48 hours (this rise can range from 60% to 100% in normal pregnancies), reach a peak at 50–75 days, and fall to lower levels in the second and third trimesters. Laboratory and home pregnancy tests use monoclonal antibodies specific for hCG. These tests are performed on serum or urine and are accurate at the time of the missed period or shortly after it.
Compared with intrauterine pregnancies, ectopic pregnancies may show lower levels of hCG that plateau or fall in serial determinations. Quantitative assays of hCG repeated at 48-hour intervals are used in the diagnosis of ectopic pregnancy as well as in cases of molar pregnancy, threatened abortion, and missed abortion. Comparison of hCG levels between laboratories may be misleading in a given patient because different international standards may produce results that vary by as much as twofold. hCG levels can also be problematic because they require a series of measurements. Progesterone levels, however, remain relatively stable in the first trimester. A single measurement of progesterone is the best indicator of whether a pregnancy is viable, although there is a broad indeterminate zone. A value < 5 ng/mL (16 nmol/L) predicts pregnancy failure while a value > 25 ng/mL (80 nmoL/L) indicates a pregnancy will be successful. There is uncertainty when the value is between these two points. Combining several serum biomarkers may provide a better prediction of pregnancy viability. Pregnancy of unknown location is a term used to describe a situation where a woman has a positive pregnancy test but the location and viability of the pregnancy is not known because nothing is seen on ultrasound.
Kirk E. Ultrasound in the diagnosis of ectopic pregnancy. Clin Obstet Gynecol. 2012 Jun;55(2):395–401. [PMID: 22510620]
The following symptoms and signs are usually due to pregnancy, but none are diagnostic. A record of the time and frequency of coitus is helpful for diagnosing and dating a pregnancy.
Amenorrhea, nausea and vomiting, breast tenderness and tingling, urinary frequency and urgency, “quickening” (perception of first movement noted at about the 18th week), weight gain.
Breast changes (enlargement, vascular engorgement, colostrum) start to occur very early in pregnancy and continue until the postpartum period. Cyanosis of the vagina and cervical portio and softening of the cervix occur in about the seventh week. Softening of the cervicouterine junction takes place in the eighth week, and generalized enlargement and diffuse softening of the corpus occurs after the eighth week. When a woman’s abdomen will start to enlarge depends on her body habitus but typically starts in the sixteenth week.
The uterine fundus is palpable above the pubic symphysis by 12–15 weeks from the last menstrual period and reaches the umbilicus by 20–22 weeks. Fetal heart tones can be heard by Doppler at 10–12 weeks of gestation.
The nonpregnant uterus enlarged by myomas can be confused with the gravid uterus, but it is usually very firm and irregular. An ovarian tumor may be found midline, displacing the nonpregnant uterus to the side or posteriorly. Ultrasonography and a pregnancy test will provide accurate diagnosis in these circumstances.
The first prenatal visit should occur as early as possible after the diagnosis of pregnancy and should include the following: history, physical examination, laboratory tests, advice to the patient, and tests and procedures.
The patient’s age, ethnic background, and occupation should be obtained. The onset of the last menstrual period and its normality, possible conception dates, bleeding after the last menstruation, medical history, all prior pregnancies (duration, outcome, and complications), and symptoms of present pregnancy should be documented. The patient’s nutritional habits should be discussed with her, as well as any use of caffeine, tobacco, alcohol, or drugs (Table 19–1 and 19–2). Whether there is any family history of congenital anomalies and heritable diseases, a personal history of childhood varicella, prior sexually transmitted diseases (STDs), or risk factors for HIV infection should be determined. The woman should also be asked about domestic violence (see Chapter 42).
Table 19–1. Common drugs that are teratogenic or fetotoxic.1
Table 19–2. Drugs and substances that require a careful assessment of risk before they are prescribed for breastfeeding women.
Height, weight, and blood pressure should be measured, and a general physical examination should be done, including a breast examination. Abdominal and pelvic examination should include the following: (1) estimate of uterine size or measure of fundal height; (2) evaluation of bony pelvis for symmetry and adequacy; (3) evaluation of cervix for structural anatomy, infection, effacement, dilation; (4) detection of fetal heart tones by Doppler device after 10 weeks.
Urinalysis; culture of a clean-voided midstream urine sample; random blood glucose; complete blood count (CBC) with red cell indices; serologic test for syphilis, rubella antibody titer; varicella immunity; blood group; Rh type; antibody screening for anti-Rho(D), hepatitis B surface antigen (HBsAg), and the HIV should be performed. Cervical cultures are usually obtained for Chlamydia trachomatis and possibly Neisseria gonorrhoeae, along with a Papanicolaou smear of the cervix. All black women should have sickle cell screening. Women of African, Asian, or Mediterranean ancestry with anemia or low mean corpuscular volume (MCV) values should have hemoglobin electrophoresis performed to identify abnormal hemoglobins (Hb S, C, F, alpha-thalassemia, beta-thalassemia). Tuberculosis skin testing is indicated for high-risk populations. Fetal aneuploidy screening is available in the first and second trimester and should be offered to all women, ideally before 20 weeks gestation. Noninvasive first trimester screening for Down syndrome includes ultrasonographic nuchal translucency and serum levels of PAPP-A (pregnancy-associated plasma protein A) and the free beta subunit of hCG. In the second trimester, a “quad screen” blood test can be performed; it measures serum alpha-fetoprotein (msAFP), beta-hCG, unconjugated estriol, and inhibin A. First and second trimester tests have similar detection rates. When first and second trimester screening are combined (integrated screening), the detection rates are even higher. For high risk pregnancies, noninvasive testing with cell free fetal DNA from maternal plasma can be performed. It screens only for trisomy 13, 18, and 21. Women at increased risk for aneuploidy can then be offered chorionic villus sampling or genetic amniocentesis, depending on gestational age and availability. Blood screening for Tay-Sachs, Canavan disease, and familial dysautonomia is offered to couples who are of Eastern European Jewish (Ashkenazi) descent. Couples of French-Canadian or Cajun ancestry should also be screened as possible Tay-Sachs carriers. Screening for cystic fibrosis is offered to all pregnant women. Hepatitis C antibody screening should be offered to pregnant women who are at high risk for infection.
Prenatal care should begin early and maintain a schedule of regular prenatal visits: 4–28 weeks, every 4 weeks; 28–36 weeks, every 2 weeks; 36 weeks on, weekly.
The patient should be counseled to eat a balanced diet containing the major food groups.
1. Prenatal vitamins with iron and folic acid should be prescribed. Supplements that are not specified for pregnant women should be avoided as they may contain dangerous amounts of certain vitamins.
2. The average weight pregnant woman should be expected to gain is 20–40 lb. A pregnant woman should not diet to lose weight during pregnancy, although obese women do seem to benefit from gaining less weight, perhaps 10–15 lb.
3. Caffeine intake should be decreased to 0–1 cup of coffee, tea, or caffeinated cola daily.
4. The patient should be advised to avoid eating raw or rare meat as well as fish known to contain elevated levels of mercury.
5. Patients should be encouraged to eat fresh fruits and vegetables (washed before eating).
Only medications prescribed or authorized by the obstetric provider should be taken.
Patients should be encouraged to abstain from alcohol, tobacco, and all recreational (“street”) drugs. No safe level of alcohol intake has been established for pregnancy. Fetal effects are manifest in the fetal alcohol syndrome, which includes growth restriction; facial, skeletal, and cardiac abnormalities; and serious central nervous system dysfunction. These effects are thought to result from direct toxicity of ethanol as well as of its metabolites such as acetaldehyde.
Cigarette smoking results in fetal exposure to carbon monoxide and nicotine, and this is thought to eventuate in a number of adverse pregnancy outcomes. An increased risk of abruptio placentae, placenta previa, and premature rupture of the membranes is documented among women who smoke. Preterm delivery, low birth weight, and ectopic pregnancy are also more likely among smokers. Women who smoke should quit smoking or at least reduce the number of cigarettes smoked per day to as few as possible. Clinicians should ask all pregnant women about their smoking history and offer smoking cessation counseling during pregnancy, since women are more motivated to change at this time. Pregnant women should also avoid exposure to environmental smoke (“passive smoking”), and smokeless tobacco, and e-cigarettes
Sometimes compounding the above effects on pregnancy outcome are the independent adverse effects of illicit drugs. Cocaine use in pregnancy is associated with an increased risk of premature rupture of membranes, preterm delivery, placental abruption, intrauterine growth restriction, neurobehavioral deficits, and sudden infant death syndrome. Similar adverse pregnancy effects are associated with amphetamine use, perhaps reflecting the vasoconstrictive potential of both amphetamines and cocaine. Adverse effects associated with opioid use include intrauterine growth restriction, prematurity, and fetal death.
Radiographs should be avoided unless essential and approved by a clinician. Abdominal shielding should be used whenever possible. The patient should be told to inform her other clinicians and dentist that she is pregnant. Chemical or radiation hazards should be avoided as should excessive heat in hot tubs or saunas. Patients should be told to avoid handling cat feces or cat litter and to wear gloves when gardening.
The patient should be encouraged to obtain adequate rest each day. She should abstain from strenuous physical work or activities, particularly when heavy lifting or weight bearing is required. Regular exercise can be continued at a mild to moderate level; however, exhausting or hazardous exercises or new athletic training programs should be avoided during pregnancy. Exercises that require a great deal of balance should also be done with caution.
The patient should be encouraged to enroll in a childbirth preparation class with her partner well before her due date.
Weight, blood pressure, fundal height, and fetal heart rate are measured, and a urine specimen is obtained and tested for protein and glucose. Any concerns the patient may have about pregnancy, health, and nutrition should be addressed.
Confirm uterine size and growth by pelvic examination. Document fetal heart tones (audible at 10–12 weeks of gestation by Doppler). First trimester screening and a discussion of choices of aneuploidy screening should be discussed at this time (see Laboratory Tests, above). If indicated and requested by the patient, chorionic villus sampling can be performed during this period (11–13 weeks).
The “quad screen” and amniocentesis are performed as indicated and requested by the patient during this time (see Laboratory Tests, above). Fetal ultrasound examination to determine pregnancy dating and evaluate fetal anatomy is also done. An earlier examination provides the most accurate dating, and a later examination demonstrates fetal anatomy in greatest detail. The best compromise is at 18–20 weeks of gestation. Cervical length measurement (> 2.5 cm is normal) for prediction of likelihood of preterm birth can also be done at this time.
The patient should be instructed about the symptoms and signs of preterm labor and rupture of membranes. Ultrasound examination is performed as indicated. Typically, fetal size and growth are evaluated when fundal height is 3 cm less than or more than expected for gestational age. In multiple pregnancies, ultrasound should be performed every 4–6 weeks to evaluate for discordant growth.
Screening for gestational diabetes is performed using a 50-g glucose load (Glucola) and a 1-hour post-Glucola blood glucose determination. Abnormal values (≥ 140 mg/dL or 7.8 mmol/L) should be followed up with a 3-hour glucose tolerance test (see Table 19–4).
If initial antibody screen for anti-Rho(D) is negative, repeat antibody testing for Rh-negative patients is performed, but the result is not required before Rho(D) immune globulin is administered (see below).
A CBC is done to evaluate for anemia of pregnancy. Screening for syphilis and HIV is also performed at this time. Providers should familiarize themselves with the laws in their state since testing requirements vary.
Fetal position and presentation are determined. The patient is asked about symptoms or signs of preterm labor or rupture of membranes at each visit. Maternal perception of fetal movement should be assessed at each visit. Antepartum fetal testing can be performed as medically indicated.
Repeat syphilis and HIV testing (depending on state laws) and cervical cultures for N gonorrhoeae and C trachomatis should be performed in at-risk patients. The indicators of onset of labor, admission to the hospital, management of labor and delivery, and options for analgesia and anesthesia should be discussed with the patient. Weekly cervical examinations are not necessary unless indicated to assess a specific clinical situation. Elective delivery (whether by induction or cesarean section) prior to 39 weeks of gestation requires confirmation of fetal lung maturity.
The CDC recommends universal prenatal culture-based screening for group B streptococcal colonization in pregnancy. A single standard culture of the distal vagina and anorectum is collected at 35–37 weeks. No prophylaxis is needed if the screening culture is negative. Patients whose cultures are positive receive intrapartum penicillin prophylaxis during labor. Except when group B streptococci are found in urine, asymptomatic colonization is not to be treated before labor. Patients who have had a previous infant with invasive group B streptococcal disease or who have group B streptococcal bacteriuria during this pregnancy should receive intrapartum prophylaxis regardless, so rectovaginal cultures are not needed. Patients whose cultures at 35–37 weeks were not done or whose results are not known should receive prophylaxis if they have a risk factor for early-onset neonatal disease, including intrapartum temperature ≥ 38°C, membrane rupture > 18 hours, or delivery before 37 weeks gestation.
The routine recommended regimen for prophylaxis is penicillin G, 5 million units intravenously as a loading dose and then 2.5 million units intravenously every 4 hours until delivery. In penicillin-allergic patients not at high risk for anaphylaxis, 2 g of cefazolin can be given intravenously as an initial dose and then 1 g intravenously every 8 hours until delivery. In patients at high risk for anaphylaxis, vancomycin 1 g intravenously every 12 hours until delivery is used or, after confirmed susceptibility testing of group B streptococcal isolate, clindamycin 900 mg intravenously every 8 hours or erythromycin 500 mg intravenously every 6 hours until delivery.
The patient should have a cervical examination to determine the probability of successful induction of labor. Based on this, induction of labor is undertaken if the cervix is favorable (generally, cervix ≥ 2 cm dilated ≥ 50% effaced, vertex at –1 station, soft cervix, and midposition); if unfavorable, antepartum fetal testing is begun. Induction is performed at 42 weeks gestation regardless of the cervical examination findings; some providers elect induction at 41 weeks regardless of the cervical examination findings.
Dooley EK et al. Prenatal care: touching the future. Prim Care. 2012 Mar;39(1):17–37. [PMID: 22309579]
O’Neill M et al. Ambulatory obstetric care. Clin Obstet Gynecol. 2012 Sep;55(3):714–21. [PMID: 22828104]
Simpson JL. Cell-free fetal DNA and maternal serum analytes for monitoring embryonic and fetal status. Fertil Steril. 2013 Mar 15;99(4):1124–34. [PMID: 23499003]
Nutrition in pregnancy can affect maternal health and infant size and well-being. Pregnant women should have nutrition counseling early in prenatal care and access to supplementary food programs if necessary. Counseling should stress abstention from alcohol, smoking, and recreational drugs. Caffeine and artificial sweeteners should be used only in small amounts.
Recommendations regarding weight gain in pregnancy should be based on maternal body mass index (BMI) preconceptionally or at the first prenatal visit. According to the Institute of Medicine guidelines, total weight gain should be 25–35 lbs (11.3–15.9 kg) for normal weight women (BMI of 18.5–24.9) and 15–25 lbs (6.8–11.3 kg) for overweight women. For obese women (BMI of 30 or greater), weight gain should be limited to 11–20 lbs (5.0–9.1 kg). Excessive maternal weight gain has been associated with increased birth weight as well as postpartum retention of weight. Not gaining weight in pregnancy, conversely, has been associated with low birth weight. Nutrition counseling must be tailored to the individual patient.
The increased calcium needs of pregnancy (1200 mg/d) can be met with milk, milk products, green vegetables, soybean products, corn tortillas, and calcium carbonate supplements.
The increased need for iron and folic acid should be met with foods as well as vitamin and mineral supplements. (See Anemia section.) Megavitamins should not be taken in pregnancy, as they may result in fetal malformation or disturbed metabolism. However, a balanced prenatal supplement containing 30–60 mg of elemental iron, 0.5–0.8 mg of folate, and the recommended daily allowances of various vitamins and minerals is widely used in the United States and is probably beneficial to many women with marginal diets. There is evidence that periconceptional folic acid supplements can decrease the risk of neural tube defects in the fetus. For this reason, the United States Public Health Service recommends the consumption of 0.4 mg of folic acid per day for all pregnant and reproductive age women. Women with a prior pregnancy complicated by neural tube defect may require higher supplemental doses as determined by their providers.
American College of Obstetricians and Gynecologists. ACOG Committee opinion no. 548: Weight gain during pregnancy. Obstet Gynecol. 2013 Jan;121(1):210–2. [PMID: 23262962]
Blumfield ML et al. A systematic review and meta-analysis of micronutrient intakes during pregnancy in developed countries. Nutr Rev. 2013 Feb;71(2):118–32. [PMID: 23356639]
Haider BA et al. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Rev. 2012 Nov 14;11:CD004905. [PMID: 23152228]
Lassi ZS et al. Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes. Cochrane Database Syst Rev. 2013 Mar 28;3:CD006896. [PMID: 23543547]
The antibody anti-Rho(D) causes severe hemolytic disease of the newborn. About 15% of whites and much lower proportions of blacks and Asians are Rho(D)–negative. If an Rho(D)–negative woman carries an Rho(D)–positive fetus, antibodies against Rho(D) may develop in the mother when fetal red cells enter her circulation during small fetomaternal bleeding episodes in the early third trimester or during delivery, abortion, ectopic pregnancy, abruptio placentae, or other instances of antepartum bleeding. This antibody, once produced, remains in the woman’s circulation and poses the threat of hemolytic disease for subsequent Rh-positive fetuses.
Passive immunization against hemolytic disease of the newborn is achieved with Rho(D) immune globulin, a purified concentrate of antibodies against Rho(D) antigen. The Rho(D) immune globulin (one vial of 300 mcg intramuscularly) is given to the mother within 72 hours after delivery (or spontaneous or induced abortion or ectopic pregnancy). The antibodies in the immune globulin destroy fetal Rh-positive cells so that the mother will not produce anti-Rho(D). During her next Rh-positive gestation, erythroblastosis will be prevented. An additional safety measure is the routine administration of the immune globulin at the 28th week of pregnancy. The passive antibody titer that results is too low to significantly affect an Rh-positive fetus. The maternal clearance of the globulin is slow enough that protection will continue for 12 weeks. Once a woman is alloimmunized, Rho(D) immune globulin is no longer helpful and should not be given.
Karanth L et al. Anti-D administration after spontaneous miscarriage for preventing Rhesus alloimmunisation. Cochrane Database Syst Rev. 2013 Mar 28;3:CD009617. [PMID: 23543581]
Moise KJ Jret al. Management and prevention of red cell alloimmunization in pregnancy: a systematic review. Obstet Gynecol. 2012 Nov;120(5):1132–9. [PMID: 23090532]
Okwundu CI et al. Intramuscular versus intravenous anti-D for preventing Rhesus alloimmunization during pregnancy. Cochrane Database Syst Rev. 2013 Jan 31;1:CD007885. [PMID: 23440818]
Breastfeeding should be encouraged by education throughout pregnancy and the puerperium. Mothers should be told the benefits of breastfeeding, including infant immunity, emotional satisfaction, mother-infant bonding, and economic savings. The period of amenorrhea associated with frequent and consistent breastfeeding provides some (although not reliable) birth control until menstruation begins at 6–12 months postpartum or the intensity of breastfeeding diminishes. If the mother must return to work, even a brief period of nursing is beneficial. Transfer of immunoglobulins in colostrum and breast milk protects the infant against many systemic and enteric infections. Macrophages and lymphocytes transferred to the infant from breast milk play an immunoprotective role. The intestinal flora of breastfed infants inhibits the growth of pathogens. Breastfed infants have fewer bacterial and viral infections, fewer gastrointestinal tract infections, and fewer allergy problems than bottle-fed infants. Furthermore, they are less apt to be obese as children and adults.
Frequent breastfeeding on an infant-demand schedule enhances milk flow and successful breastfeeding. Mothers breastfeeding for the first time need help and encouragement from providers, nurses, and other nursing mothers. Milk supply can be increased by increased suckling and increased rest.
Nursing mothers should have a fluid intake of over 3 L/d. The United States RDA calls for 21 g of extra protein (over the 44 g/d baseline for an adult woman) and 550 extra kcal/d in the first 6 months of nursing. Calcium intake should be 1200 mg/d. Continuation of a prenatal vitamin and mineral supplement is wise. Strict vegetarians who eschew both milk and eggs should always take vitamin B12supplements during pregnancy and lactation.
Drugs taken by a nursing mother may accumulate in milk and be transmitted to the infant (Table 19–2). The amount of drug entering the milk depends on the drug’s lipid solubility, mechanism of transport, and degree of ionization.
The simplest and safest method of suppressing lactation after it has started is to gradually transfer the baby to a bottle or a cup over a 3-week period. Milk supply will decrease with decreased demand, and minimal discomfort ensues. If nursing must be stopped abruptly, the mother should avoid nipple stimulation, refrain from expressing milk, and use a snug brassiere. Ice packs and analgesics can be helpful. This same technique can be used in cases where suppression is desired before nursing has begun. Engorgement will gradually recede over a 2- to 3-day period. Hormonal suppression of lactation is no longer practiced.
Johnston M et al. Breastfeeding and the use of human milk. Pediatrics. 2012 Mar;129(3):e827–41. [PMID: 22371471]
Oladapo OT et al. Treatments for suppression of lactation. Cochrane Database Syst Rev. 2012 Sep 12;9:CD005937. [PMID: 22972088]
During an otherwise normal low-risk pregnancy, travel can be planned most safely up to the 32nd week. Commercial flying in pressurized cabins does not pose a threat to the fetus. An aisle seat will allow frequent walks. Adequate fluids should be taken during the flight.
It is not advisable to travel to endemic areas of yellow fever in Africa or Latin America; similarly, it is inadvisable to travel to areas of Africa or Asia where chloroquine-resistant falciparum malaria is a hazard, since complications of malaria are more common in pregnancy.
Ideally, all immunizations should precede pregnancy. Live virus products are contraindicated during pregnancy (measles, rubella, yellow fever and smallpox.) Inactivated polio vaccine (IPV) should be given subcutaneously instead of the oral live-attenuated vaccine. The varicella vaccine should be given 1–3 months before becoming pregnant. Vaccines against pneumococcal pneumonia, meningococcal meningitis, and hepatitis A can be used as indicated. Pregnant women who are considered to be at high-risk for hepatitis B and who have not been previously vaccinated should be vaccinated during pregnancy.
Annual influenza vaccination is indicated in all women who are pregnant or will be pregnant during “flu season.” It can be given in the first trimester. The CDC lists pregnant women as a high-risk group. In October 2012, the CDC’s Advisory Committee on Immunization Practices recommended that every pregnant woman should receive a dose of Tdap during each pregnancy irrespective of her prior vaccination history. The optimal timing for such Tdap administration is between 27 and 36 weeks of gestation, in order to maximize the antibody response of the pregnant woman and the passive antibody transfer to the infant. For any woman who was not previously vaccinated with Tdap and for whom the vaccine was not given during her pregnancy, Tdap should be administered immediately postpartum. Further, any teenagers or adults not previously vaccinated who will have close contact with the infant should also receive it, ideally 2 weeks before exposure to the child. This vaccination strategy is referred to as “cocooning,” and its purpose is to protect the infant aged < 12 months who is at particularly high risk for lethal pertussis.
Hepatitis A vaccine contains formalin-inactivated virus and can be given in pregnancy when needed. Pooled immune globulin to prevent hepatitis A is safe and does not carry risk of HIV transmission.
Chloroquine can be used for malaria prophylaxis in pregnancy, and proguanil is also safe.
Water should be purified by boiling, since iodine purification may provide more iodine than is safe during pregnancy.
Prophylactic antibiotics or bismuth subsalicylate should not be used during pregnancy to prevent diarrhea. Oral rehydration and treatment of bacterial diarrhea with erythromycin or ampicillin if necessary is preferred.
Centers for Disease Control and Prevention (CDC). Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) in pregnant women—Advisory Committee on Immunization Practices (ACIP), 2012. MMWR Morb Mortal Wkly Rep. 2013 Feb 22;62(7):131–5. [PMID: 23425962]
ESSENTIALS OF DIAGNOSIS
Morning or evening nausea and vomiting.
Persistent vomiting severe enough to result in weight loss, dehydration, starvation ketosis, hypochloremic alkalosis, hypokalemia.
May have transient elevation of liver enzymes.
Appears related to high or rising serum hCG.
More common with multiple gestation or hydatidiform mole.
Nausea and vomiting begin soon after the first missed period and cease by the fifth month of gestation. Up to three-fourths of women complain of nausea and vomiting during early pregnancy, with the vast majority noting nausea throughout the day. This problem exerts no adverse effects on the pregnancy and does not presage other complications.
Persistent, severe vomiting during pregnancy—hyperemesis gravidarum—can be disabling and require hospitalization. Thyroid dysfunction can be associated with hyperemesis gravidarum, so it is advisable to determine thyroid-stimulating hormone (TSH) and free thyroxine (FT4) values in these patients.
In most instances, only reassurance and dietary advice are required. Because of possible teratogenicity, drugs used during the first half of pregnancy should be restricted to those of major importance to life and health. Antiemetics, antihistamines, and antispasmodics are generally unnecessary to treat nausea of pregnancy. Vitamin B6 (pyridoxine), 50–100 mg/d orally, is nontoxic and may be helpful in some patients.
With more severe nausea and vomiting, it may become necessary to hospitalize the patient. In this case, a private room with limited activity is preferred. Give nothing by mouth for 48 hours, and maintain hydration and electrolyte balance by giving appropriate parenteral fluids and vitamin supplements as indicated. Antiemetics such as promethazine (25 mg orally, rectally, or intravenously every 4–6 hours), metoclopramide (10 mg orally or intravenously every 6 hours), or ondansetron (4–8 mg orally or intravenously every 8 hours) should be started. Antiemetics will likely need to be given intravenously initially. Rarely, total parenteral nutrition may become necessary. As soon as possible, place the patient on a dry diet consisting of six small feedings daily plus clear liquids 1 hour after eating. Antiemetics may be continued orally as needed. After in-patient stabilization, the patient can be maintained at home even if she requires intravenous fluids in addition to her oral intake. There are conflicting studies regarding the use of corticosteroids for the control of hyperemesis gravidarum. Therefore, this treatment should be withheld until more accepted treatments have been exhausted.
• Patient is unable to tolerate any food or water.
• There is concern for other pathology (ie, hydatidiform mole).
• Patient requires hospitalization.
• Patient is unable to tolerate any food or water.
• Condition precludes the patient from ingesting necessary medications.
• Weight loss.
• Presence of a hydatidiform mole.
Kashifard M et al. Ondansetrone or metoclopromide? Which is more effective in severe nausea and vomiting of pregnancy? A randomized trial double-blind study. Clin Exp Obstet Gynecol. 2013;40(1):127–30. [PMID: 23724526]
Niebyl JR. Clinical practice. Nausea and vomiting in pregnancy. N Engl J Med. 2010 Oct 14;363(16):1544–50. [PMID: 20942670]
Sonkusare S. The clinical management of hyperemesis gravidarum. Arch Gynecol Obstet. 2011 Jun;283(6):1183–92. [PMID: 21424548]
Tan PC et al. Dextrose saline compared with normal saline rehydration of hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2013 Feb;121(2 Pt 1):291–8. [PMID: 23232754]
ESSENTIALS OF DIAGNOSIS
Intrauterine pregnancy at < 20 weeks.
Low or falling levels of hCG.
Bleeding, midline cramping pain.
Open cervical os.
Complete or partial expulsion of products of conception.
About three-fourths of spontaneous abortions occur before the 16th week; of these, three-fourths occur before the eighth week. Almost 20% of all clinically recognized pregnancies terminate in spontaneous abortion.
More than 60% of spontaneous abortions result from chromosomal defects due to maternal or paternal factors; about 15% appear to be associated with maternal trauma, infections, dietary deficiencies, diabetes mellitus, hypothyroidism, the lupus anticoagulant-anticardiolipin-antiphospholipid antibody syndrome, or anatomic malformations. There is no reliable evidence that abortion may be induced by psychic stimuli such as severe fright, grief, anger, or anxiety. In about one-fourth of cases, the cause of abortion cannot be determined. There is no evidence that video display terminals or associated electromagnetic fields are related to an increased risk of spontaneous abortion.
It is important to distinguish women with a history of incompetent cervix from those with more typical early abortion. Characteristically, incompetent cervix presents as “silent” cervical dilation (ie, with minimal uterine contractions) in the second trimester. Women with incompetent cervix often present with significant cervical dilation (2 cm or more) and minimal symptoms. When the cervix reaches 4 cm or more, active uterine contractions or rupture of the membranes may occur secondary to the degree of cervical dilation. This does not change the primary diagnosis. Factors that predispose to incompetent cervix are a history of incompetent cervix with a previous pregnancy, cervical conization or surgery, cervical injury, diethylstilbestrol (DES) exposure, and anatomic abnormalities of the cervix. Prior to pregnancy or during the first trimester, there are no methods for determining whether the cervix will eventually be incompetent. After 14–16 weeks, ultrasound may be used to evaluate the internal anatomy of the lower uterine segment and cervix for the funneling and shortening abnormalities consistent with cervical incompetence.
1. Threatened abortion—Bleeding or cramping occurs, but the pregnancy continues. The cervix is not dilated.
2. Inevitable abortion—The cervix is dilated and the membranes may be ruptured, but passage of the products of conception has not yet occurred. Bleeding and cramping persist, and passage of the products of conception is considered inevitable.
3. Complete abortion—Products of conception are completely expelled. Pain ceases, but spotting may persist. Cervical os is closed.
4. Incomplete abortion—The cervix is dilated. Some portion of the products of conception (usually placental) remains in the uterus. Only mild cramps are reported, but bleeding is persistent and often excessive.
5. Missed abortion—The pregnancy has ceased to develop, but the conceptus has not been expelled. Symptoms of pregnancy disappear. There may be a brownish vaginal discharge but no active bleeding. Pain does not develop. The cervix is semifirm and slightly patulous; the uterus becomes smaller and irregularly softened; the adnexa are normal.
Pregnancy tests show low or falling levels of hCG. A CBC should be obtained if bleeding is heavy. Determine Rh type, and give Rho (D) immune globulin if Rh-negative. All tissue recovered should be assessed by a pathologist and may be sent for genetic analysis in selected cases.
The gestational sac can be identified at 5–6 weeks from the last menstruation, a fetal pole at 6 weeks, and fetal cardiac activity at 6–7 weeks by transvaginal ultrasound. Serial observations are often required to evaluate changes in size of the embryo. A small, irregular sac without a fetal pole with accurate dating is diagnostic of an abnormal pregnancy.
The bleeding that occurs in abortion of a uterine pregnancy must be differentiated from the abnormal bleeding of an ectopic pregnancy and anovular bleeding in a nonpregnant woman. The passage of hydropic villi in the bloody discharge is diagnostic of hydatidiform mole.
1. Threatened abortion—The patient should be placed on bed rest for 24–48 hours followed by gradual resumption of usual activities, with abstinence from coitus and douching. Hormonal treatment is contraindicated. Antibiotics should be used only if there are signs of infection.
2. Missed abortion—This calls for counseling regarding the fate of the pregnancy and planning for its elective termination at a time chosen by the patient and clinician. Insertion of laminaria to dilate the cervix followed by aspiration has historically been the method of choice for a missed abortion. Medically induced first-trimester termination with prostaglandins (ie, misoprostol given vaginally or orally in a dose of 200–800 mcg) combined with an antiprogesterone (ie, mifepristone 600 mg orally) has grown in popularity because it has been shown to be safe, effective, less invasive, and more private. If it is unsuccessful or if there is excessive bleeding, a surgical procedure may still be needed. Patients must be counseled about the different therapeutic options with a thorough explanation of all risks and benefits.
1. Incomplete or inevitable abortion—Prompt removal of any products of conception remaining within the uterus is required to stop bleeding and prevent infection. Analgesia and a paracervical block are useful, followed by uterine exploration with ovum forceps or uterine aspiration. Regional anesthesia may be required.
2. Cerclage and restriction of activities—A cerclage is the treatment of choice for incompetent cervix, but a viable intrauterine pregnancy should be confirmed prior to placement of the cerclage.
A variety of suture materials including a 5-mm Mersilene tape or No. 2 nonabsorbable monofilament suture can be used to create a purse-string type of stitch around the cervix, using either the McDonald or Shirodkar method. Cerclage should be undertaken with caution when there is advanced cervical dilation or when the membranes are prolapsed into the vagina. Rupture of the membranes and infection are specific contraindications to cerclage. Cervical cultures for N gonorrhoeae, C trachomatis, and group B streptococci should be obtained before elective placement of a cerclage. N gonorrhoeaeand C trachomatis should be treated before placement.
• Patient with history of two second-trimester losses.
• Vaginal bleeding in a pregnant patient that resembles menstruation in a nonpregnant woman.
• Patient with an open cervical os.
• No signs of uterine growth in serial examinations of a pregnant patient.
• Leakage of amniotic fluid.
• Open cervical os.
• Heavy vaginal bleeding.
• Leakage of amniotic fluid.
Brix N et al; CERVO group. Randomised trial of cervical cerclage, with and without occlusion, for the prevention of preterm birth in women suspected for cervical insufficiency. BJOG. 2013 Apr;120(5):613–20. [PMID: 23331924]
Martonffy AI et al. First trimester complications. Prim Care. 2012 Mar;39(1):71–82. [PMID: 22309582]
Neilson JP et al. Medical treatments for incomplete miscarriage. Cochrane Database Syst Rev. 2013 Mar 28;3:CD007223. [PMID: 23543549]
Recurrent abortion has been defined as the loss of three or more previable (< 20 weeks gestation or 500 g) pregnancies in succession. Recurrent abortion occurs in about 1% of all couples. Abnormalities related to recurrent abortion can be identified in approximately half of these instances. If a woman has lost three previous pregnancies without identifiable cause, she still has at least a 65% chance of carrying a fetus to viability.
Recurrent abortion is a clinical rather than pathologic diagnosis. The clinical findings are similar to those observed in other types of abortion (see above).
Preconception therapy is aimed at detection of maternal or paternal defects that may contribute to abortion. A thorough history and examination is essential. A random blood glucose test and thyroid function studies (including thyroid antibodies) can be done if history indicates a possible predisposition to diabetes mellitus or thyroid disease. Detection of lupus anticoagulant and other hemostatic abnormalities (proteins S and C and antithrombin deficiency, hyperhomocysteinemia, anticardiolipin antibody, factor V Leiden mutations) and an antinuclear antibody test may be indicated. Hysteroscopy or hysterography can be used to exclude submucosal myomas and congenital anomalies of the uterus. In women with recurrent losses, resection of a uterine septum, if present, has been recommended. Chromosomal (karyotype) analysis of both partners can be done to rule out balanced translocations (found in 5% of infertile couples), but karyotyping is expensive and may not be helpful.
Many therapies have been tried to prevent recurrent pregnancy loss from immunologic causes. Low-molecular-weight heparin (LMWH), aspirin, intravenous immunoglobulin, and corticosteroids have all been used but the definitive treatment has not yet been determined. Prophylactic dose heparin and low-dose aspirin have been recommended for women with antiphospholipid antibodies and recurrent pregnancy loss.
The patient should be provided early prenatal care and scheduled frequent office visits. Bed rest is justified only for bleeding or pain. Empiric sex steroid hormone therapy is contraindicated.
The prognosis is excellent if the cause of abortion can be corrected or treated.
American College of Obstetricians and Gynecologists. Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol. 2012 Dec;120(6):1514–21. [PMID: 23168789]
Branch DW et al. Clinical practice. Recurrent miscarriage. N Engl J Med. 2010 Oct;363(18):1740–7. [PMID: 20979474]
Practice Committee of American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: a committee opinion. Fertil Steril. 2013 Jan;99(1):63. [PMID: 23095139]
ESSENTIALS OF DIAGNOSIS
Amenorrhea or irregular bleeding and spotting.
Pelvic pain, usually adnexal.
Adnexal mass by clinical examination or ultrasound.
Failure of serum level of beta-hCG to double every 48 hours.
No intrauterine pregnancy on transvaginal ultrasound with serum beta-hCG > 2000 mU/mL.
Ectopic implantation occurs in about one out of 150 live births. About 98% of ectopic pregnancies are tubal. Other sites of ectopic implantation are the peritoneum or abdominal viscera, the ovary, and the cervix. Any condition that prevents or retards migration of the fertilized ovum to the uterus can predispose to an ectopic pregnancy, including a history of infertility, pelvic inflammatory disease, ruptured appendix, and prior tubal surgery. Combined intrauterine and extrauterine pregnancy (heterotopic) may occur rarely. In the United States, undiagnosed or undetected ectopic pregnancy is one of the most common causes of maternal death during the first trimester.
Severe lower quadrant pain occurs in almost every case. It is sudden in onset, stabbing, intermittent, and does not radiate. Backache may be present during attacks. Shock occurs in about 10%, often after pelvic examination. At least two-thirds of patients give a history of abnormal menstruation; many have been infertile.
Blood may leak from the tubal ampulla over a period of days, and considerable blood may accumulate in the peritoneum. Slight but persistent vaginal spotting is usually reported, and a pelvic mass may be palpated. Abdominal distention and mild paralytic ileus are often present.
The CBC may show anemia and slight leukocytosis. Quantitative serum pregnancy tests will show levels generally lower than expected for normal pregnancies of the same duration. If beta-hCG levels are followed over a few days, there may be a slow rise or a plateau rather than the near doubling every 2 days associated with normal early intrauterine pregnancy or the falling levels that occur with spontaneous abortion. A progesterone level can also be measured to assess the viability of the pregnancy.
Ultrasonography can reliably demonstrate a gestational sac 5–6 weeks from the last menstruation and a fetal pole at 6 weeks if located in the uterus. An empty uterine cavity raises a strong suspicion of extrauterine pregnancy, which can occasionally be revealed by transvaginal ultrasound. Specified levels of serum beta-hCG have been reliably correlated with ultrasound findings of an intrauterine pregnancy. For example, a beta-hCG level of 6500 mU/mL with an empty uterine cavity by transabdominal ultrasound is highly suspicious for an ectopic pregnancy. Similarly, a beta-hCG value of 2000 mU/mL or more can be indicative of an ectopic pregnancy if no products of conception are detected within the uterine cavity by transvaginal ultrasound. Serum beta-hCG values can vary by laboratory.
With the advent of high-resolution transvaginal ultrasound, culdocentesis is rarely used in evaluation of possible ectopic pregnancy. Laparoscopy is the surgical procedure of choice both to confirm an ectopic pregnancy and in most cases to permit removal of the ectopic pregnancy without the need for exploratory laparotomy.
Clinical and laboratory findings suggestive or diagnostic of pregnancy will distinguish ectopic pregnancy from many acute abdominal illnesses such as acute appendicitis, acute pelvic inflammatory disease, ruptured corpus luteum cyst or ovarian follicle, and urinary calculi. Uterine enlargement with clinical findings similar to those found in ectopic pregnancy is also characteristic of an aborting uterine pregnancy or hydatidiform mole. Ectopic pregnancy should be suspected when postabortal tissue examination fails to reveal chorionic villi. Steps must be taken for immediate diagnosis, including prompt microscopic tissue examination, ultrasonography, and serial beta-hCG titers every 48 hours.
Patients must be warned about the complications of an ectopic pregnancy and monitored closely. In a stable patient, methotrexate (50 mg/m2) intramuscularly—given as single or multiple doses—is acceptable medical therapy for early ectopic pregnancy. Favorable criteria are that the pregnancy should be < 3.5 cm in largest dimension and unruptured, with no active bleeding and no fetal heart tones.
When a patient with an ectopic pregnancy is unstable or when surgical therapy is planned, the patient is hospitalized. Blood is typed and cross-matched. Ideally, diagnosis and operative treatment should precede frank rupture of the tube and intra-abdominal hemorrhage. The use of methotrexate in an unstable patient is absolutely contraindicated.
Surgical treatment is definitive. In most patients, diagnostic laparoscopy is the initial surgical procedure performed. Depending on the size of the ectopic pregnancy and whether or not it has ruptured, salpingostomy with removal of the ectopic or a partial or complete salpingectomy can usually be performed. Clinical conditions permitting, patency of the contralateral tube can be established by injection of indigo carmine into the uterine cavity and flow through the contralateral tube confirmed visually by the surgeon; iron therapy for anemia may be necessary during convalescence. Rho(D) immune globulin (300 mcg) should be given to Rh-negative patients.
Repeat tubal pregnancy occurs in about 10% of cases. This should not be regarded as a contraindication to future pregnancy, but the patient requires careful observation and early ultrasound confirmation of an intrauterine pregnancy.
• Severe abdominal pain.
• Palpation of an adnexal mass on pelvic examination.
• Abdominal pain and vaginal bleeding in a pregnant patient.
• Presence of symptoms or signs of a ruptured ectopic pregnancy.
Crochet JR et al. Does this woman have an ectopic pregnancy?: the rational clinical examination systematic review. JAMA. 2013 Apr 24;309(16):1722–9. [PMID: 23613077]
Lispcomb GH. Medical management of ectopic pregnancy. Clin Obstet Gynecol. 2012 Jun;55(2):424–32. [PMID: 22510624]
Torpy JM et al. JAMA patient page. Ectopic pregnancy. JAMA. 2012 Aug 22;308(8):829. [PMID: 22910764]
van Mello NM et al. Diagnostic value of serum hCG on the outcome of pregnancy of unknown location: a systematic review and meta-analysis. Hum Reprod Update. 2012 Nov–Dec;18(6):603–17. [PMID: 22956411]
van Mello NM et al. Ectopic pregnancy: how the diagnostic and therapeutic management has changed. Fertil Steril. 2012 Nov;98(5):1066–73. [PMID: 23084008]
ESSENTIALS OF DIAGNOSIS
Irregular uterine bleeding.
Serum beta-hCG > 40,000 mU/mL.
Passage of grapelike clusters of enlarged edematous villi per vagina.
Ultrasound of uterus shows characteristic heterogeneous echogenic image and no fetus or placenta.
Cytogenetic composition is 46, XX (85%), completely of paternal origin.
Persistence of detectable beta-hCG after mole evacuation.
Gestational trophoblastic disease is a spectrum of disorders that includes hydatidiform mole (partial and complete), invasive mole (local extension into the uterus or vagina), choriocarcinoma (malignancy often complicated by distant metastases), and placental site trophoblastic tumor. Complete moles show no evidence of a fetus on ultrasonography. The majority are 46, XX with all chromosomes of paternal origin. Partial moles generally show evidence of an embryo or gestational sac; are triploid, slower-growing, and less symptomatic; and often present clinically as a missed abortion. Partial moles tend to follow a benign course, while complete moles have a greater tendency to become choriocarcinomas.
In the United States, the frequency of gestational trophoblastic disease is 1:1500 pregnancies. The highest rates occur in Asians. Risk factors include prior spontaneous abortion, a history of mole, and age younger than 21 or older than 35. Approximately 10% of women require further treatment after evacuation of the mole; choriocarcinoma develops in 2–3% of women.
Uterine bleeding, beginning at 6–16 weeks, is observed in most instances. In some cases, the uterus is larger than would be expected in a normal pregnancy of the same duration. Excessive nausea and vomiting may occur. Bilaterally enlarged cystic ovaries are sometimes palpable. They are the result of ovarian hyperstimulation due to excess beta-hCG.
Preeclampsia-eclampsia may develop during the second trimester of an untreated molar pregnancy, but this is unusual because most are diagnosed early.
Choriocarcinoma may be manifested by continued or recurrent uterine bleeding after evacuation of a mole or following delivery, abortion, or ectopic pregnancy. The presence of an ulcerative vaginal tumor, pelvic mass, or distant metastases may be the presenting manifestation.
Hydatidiform moles are generally characterized by high serum beta-hCG values, which can range from high normal to the millions. Levels are higher with complete moles than with partial moles. Serum beta-hCG values, if extremely high, can assist in making the diagnosis, but they are more helpful in managing response to treatment. Hematocrit, creatinine, blood type, liver function tests, and thyroid function tests should also be measured. High beta-hCG levels can cause the release of thyroid hormone, and rarely, symptoms of hyperthyroidism. Patients with hyperthyroidism may require beta-blocker therapy until the mole has been evacuated.
Ultrasound has virtually replaced all other means of preoperative diagnosis of hydatidiform mole. Placental vesicles can be easily seen on transvaginal ultrasound. A preoperative chest film is indicated to rule out pulmonary metastases of the trophoblast.
The uterus should be emptied as soon as the diagnosis of hydatidiform mole is established, preferably by suction curettage. Ovarian cysts should not be resected nor ovaries removed; spontaneous regression of theca lutein cysts will occur with elimination of the mole. The products of conception removed from the uterus should be sent to a pathologist for review. In patients who have completed their childbearing, hysterectomy is an acceptable alternative. Hysterectomy does not preclude the need for follow-up of beta-hCG levels.
Weekly quantitative beta-hCG level measurements are initially required. Following successful surgical evacuation, moles show a progressive decline in beta-hCG. After three negative weekly tests (< 5 mU/mL), the interval may be increased to every 1–3 months for an additional 6 months. The purpose of this follow-up is to identify persistent metastatic and nonmetastatic disease, including choriocarcinoma, which is more likely to occur if the initial beta-hCG is high and the uterus is large. If levels plateau or begin to rise, the patient should be evaluated by repeat laboratory tests, chest film, and dilatation and curettage (D&C) before the initiation of chemotherapy. Effective contraception (preferably birth control pills) should be prescribed to avoid the hazard and confusion of elevated beta-hCG from a new pregnancy. The beta-hCG levels should be negative for 6 months before pregnancy is attempted again. Because the risk of recurrence of a molar pregnancy is 1%, an ultrasound should be performed in the first trimester of the pregnancy following a mole to ensure that the pregnancy is normal. In addition, a beta-hCG level should then be checked 6 weeks postpartum (after the subsequent normal pregnancy) to ensure there is no persistent trophoblastic tissue, and the placenta should be examined by a pathologist.
If malignant tissue is discovered at surgery or during the follow-up examination, chemotherapy is indicated. For low-risk patients with a good prognosis, methotrexate is considered first-line therapy followed by actinomycin (see Table 39–11). Patients with a poor prognosis should be referred to a cancer center, where multiple-agent chemotherapy probably will be given.
Five-year survival after courses of chemotherapy, even when metastases have been demonstrated, can be expected in at least 85% of cases of choriocarcinoma.
• Uterine size exceeds that anticipated for gestational age.
• Vaginal bleeding similar to menstruation.
• Pregnant patient with a history of a molar pregnancy.
• Confirmed molar pregnancy by ultrasound and laboratory studies.
• Heavy vaginal bleeding in a pregnant patient under evaluation.
Deng L et al. Combination chemotherapy for primary treatment of high-risk gestational trophoblastic tumour. Cochrane Database Syst Rev. 2013 Jan 31;1:CD005196. [PMID: 23440800]
Lurain JR. Gestational trophoblastic disease I: epidemiology, pathology, clinical presentation and diagnosis of gestational trophoblastic disease, and management of hydatidiform mole. Am J Obstet Gynecol. 2010 Dec;203(6):531–9. [PMID: 20728069]
Seckl MJ et al. Gestational trophoblastic disease. Lancet. 2010 Aug 28;376(9742):717–29. [PMID: 20673583]
ESSENTIALS OF DIAGNOSIS
Blood pressure of ≥ 140 mm Hg systolic or ≥ 90 mm Hg diastolic after 20 weeks of gestation.
Proteinuria of ≥ 0.3 g in 24 hours.
Severe Preeclampsia (one or more of below)
Blood pressure of ≥ 160 mm Hg systolic or ≥ 110 mm Hg diastolic.
Progressive renal insufficiency.
Hemolysis, elevated liver enzymes, low platelets (HELLP).
Vision changes or headache.
Seizures in a patient with evidence of preeclampsia.
Preeclampsia is defined as the presence of newly elevated blood pressure and proteinuria during pregnancy. Eclampsia is diagnosed when seizures develop in a patient with evidence of preeclampsia. Historically, the presence of three elements was required for the diagnosis of preeclampsia: hypertension, proteinuria, and edema. Edema was difficult to objectively quantify and is no longer a required element.
Preeclampsia-eclampsia can occur any time after 20 weeks of gestation and up to 6 weeks postpartum. It is a disease unique to pregnancy, with the only cure being delivery of the fetus and placenta. Preeclampsia-eclampsia develops in approximately 7% of pregnant women in the United States. Primiparas are most frequently affected; however, the incidence of preeclampsia-eclampsia is increased with multiple gestation pregnancies, chronic hypertension, diabetes mellitus, kidney disease, collagen-vascular and autoimmune disorders, and gestational trophoblastic disease. Five percent of women with preeclampsia progress to eclampsia. Uncontrolled eclampsia is a significant cause of maternal death. The cause of preeclampsia-eclampsia is not known.
Clinically, the severity of preeclampsia-eclampsia can be measured with reference to the six major sites in which it exerts its effects: the central nervous system, the kidneys, the liver, the hematologic system, the vascular system, and the fetal-placental unit. By evaluating each of these areas for the presence of mild to severe preeclampsia, the degree of involvement can be assessed, and an appropriate management plan can be formulated that balances the severity of disease and gestational age (Table 19–3).
Table 19–3. Indicators of mild to moderate versus severe preeclampsia-eclampsia.
1. Mild—Patients usually have few complaints, and the diastolic blood pressure is < 110 mm Hg. Edema may be present. The platelet count is over 100,000/mcL, antepartum fetal testing is reassuring, central nervous system irritability is minimal, epigastric pain is not present, and liver enzymes are not elevated.
2. Severe—Symptoms are more dramatic and persistent. Patients may complain of headache and changes in vision. The blood pressure is often quite high, with readings at or above 160/110 mm Hg. Thrombocytopenia (platelet counts < 100,000/mcL) may be present and progress to disseminated intravascular coagulation. Severe epigastric pain may be present from hepatic subcapsular hemorrhage with significant stretch or rupture of the liver capsule. HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) is a form of severe preeclampsia.
The occurrence of seizures defines eclampsia. It is a manifestation of severe central nervous system involvement. Other findings of preeclampsia are observed.
Preeclampsia-eclampsia can mimic and be confused with many other diseases, including chronic hypertension, chronic kidney disease, primary seizure disorders, gallbladder and pancreatic disease, immune thrombocytopenia, thrombotic thrombocytopenic purpura, and hemolytic-uremic syndrome. It must always be considered, possible in any pregnant woman beyond 20 weeks of gestation. It is particularly difficult to diagnose when a preexisting disease such as hypertension is present.
In clinical studies, diuretics, dietary restriction or enhancement, sodium restriction, and vitamin-mineral supplements (eg, calcium or vitamin C and E) have not been confirmed to be useful. The only cure is delivery of the fetus at a time as favorable as possible for its survival.
Early recognition is the key to treatment. This requires careful attention to the details of prenatal care—especially subtle changes in blood pressure and weight. The objectives are to prolong pregnancy if possible, to allow fetal lung maturity while preventing progression to severe disease and eclampsia. The critical factors are the gestational age of the fetus, fetal pulmonary maturity, and the severity of maternal disease. Preeclampsia-eclampsia at term is managed by delivery. Prior to term, severe preeclampsia-eclampsia requires delivery with very few exceptions. Epigastric pain, severe range blood pressures, thrombocytopenia, and visual disturbances are strong indications for delivery of the fetus. Marked proteinuria alone can be managed more conservatively.
For mild preeclampsia, modified bed rest is the cornerstone of therapy. This increases central blood flow to the kidneys, heart, brain, liver, and placenta and may stabilize or even improve the degree of preeclampsia-eclampsia for a period of time.
Modified bed rest may be attempted at home or in the hospital. The goal is not to keep the woman in bed continuously but rather to limit her activity. Prior to making this decision, the clinician should evaluate the six sites of involvement listed in Table 19–3 and make an assessment about the severity of disease.
1. Home management—Home management with modified bed rest may be attempted for patients with mild preeclampsia and a stable home situation. This requires assistance at home, rapid access to the hospital, a reliable patient, and the ability to obtain frequent blood pressure readings. A home health nurse can often provide frequent home visits and assessments.
2. Hospital care—Hospitalization is required for women with severe preeclampsia or those with unreliable home situations. Regular assessments of blood pressure, urine protein, and fetal heart tones and activity are required. A CBC with platelet count, electrolyte panel, and liver enzymes should be checked regularly, with frequency dependent on severity. A 24-hour urine collection for total protein and creatinine clearance should be obtained on admission and repeated as indicated. Magnesium sulfate is not used until the diagnosis of severe preeclampsia is made and delivery planned (see Eclampsia, below).
Fetal evaluation should be obtained as part of the work-up. If the patient is being admitted to the hospital, fetal testing should be performed on the same day to assess fetal wellbeing. This may be done by fetal heart rate testing with nonstress testing or by biophysical profile. A regular schedule of fetal surveillance must then be followed. Daily fetal kick counts can be recorded by the patient herself. If the fetus is < 34 weeks gestation, corticosteroids (betamethasone 12 mg intramuscularly every 24 h for two doses, or dexamethasone 6 mg intramuscularly every 12 h for four doses) can be administered to the mother. However, when a woman is clearly suffering from unstable severe preeclampsia, delivery should not be delayed for fetal lung maturation or administration of corticosteroids.
The method of delivery is determined by the maternal and fetal status. A vaginal delivery is preferred because it has less blood loss than a cesarean section and requires less coagulation factors. Cesarean section is reserved for the usual fetal indications. For mild preeclampsia, delivery should take place at term.
1. Emergency care—If the patient is convulsing, she is turned on her side to prevent aspiration and to improve blood flow to the placenta. The seizure may be stopped by giving an intravenous bolus of either magnesium sulfate, 4–6 g, or lorazepam, 2–4 mg over 4 minutes or until the seizure stops. Magnesium sulfate is the preferred agent, and alternatives should only be used if magnesium sulfate is unavailable. A continuous intravenous infusion of magnesium sulfate is then started at a rate of 2–3 g/h unless the patient is known to have significantly reduced kidney function. Magnesium blood levels are then checked every 4–6 hours and the infusion rate adjusted to maintain a therapeutic blood level (4–6 mEq/L). Urinary output is checked hourly and the patient assessed for signs of possible magnesium toxicity such as loss of deep tendon reflexes or decrease in respiratory rate and depth, which can be reversed with calcium gluconate, 1 g intravenously over 2 minutes.
2. General care—In patients with severe preeclampsia, magnesium sulfate should be given intravenously, 4- to 6-g load over 15–20 minutes followed by 2–3 g/h maintenance, for seizure prophylaxis. The occurrence of eclampsia necessitates delivery once the patient is stabilized. It is important, however, that assessment of the status of the patient and fetus take place first. Continuous fetal monitoring must be performed and maternal blood typed and cross-matched quickly. A urinary catheter is inserted to monitor urinary output, and a CBC with platelets, electrolytes, creatinine, and liver enzymes are obtained. If hypertension is present with systolic values of ≥ 160 mm Hg or diastolic values ≥ 110 mm Hg, antihypertensive medications should be administered to reduce the blood pressure to 140–150/90–100 mm Hg. Lower blood pressures than this may induce placental insufficiency through reduced perfusion. Hydralazine given in 5- to 10-mg increments intravenously every 20 minutes is frequently used to lower blood pressure. Labetalol, 10–20 mg intravenously, every 20 minutes as needed, can also be used.
3. Delivery—Delivery is mandated once eclampsia has occurred. Vaginal delivery is preferred. The rapidity with which delivery must be achieved depends on the fetal and maternal status following the seizure and the availability of laboratory data on the patient. Oxytocin, given intravenously and titrated to a dose that results in adequate contractions, may be used to induce or augment labor. Oxytocin should only be administered by a clinician specifically trained in its use. Regional analgesia or general anesthesia is acceptable. Cesarean section is used for the usual obstetric indications.
4. Postpartum—Magnesium sulfate infusion (2–3 g/h) should be continued for 24 hours postpartum. Late-onset preeclampsia-eclampsia can occur during the postpartum period. It is usually manifested by either hypertension or seizures. Treatment is the same as prior to delivery—ie, with hydralazine and magnesium sulfate.
• New onset of hypertension and proteinuria in a pregnant patient > 20 weeks’ gestation.
• New onset of seizure activity in a pregnant patient.
• Symptoms of severe preeclampsia in a pregnant patient with elevated blood pressure above baseline.
• Evidence of severe preeclampsia or eclampsia.
• Evaluation for preeclampsia when severe disease is suspected.
• Evaluation for preeclampsia in a patient with an unstable home environment.
Abildgaard U et al. Pathogenesis of the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP): a review. Eur J Obstet Gynecol Reprod Biol. 2013 Feb;166(2): 117–23. [PMID: 23107053]
American College of Obstetricians and Gynecologists et al. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol. 2013 Nov;122(5): 1122–31. [PMID: 24150027]
Repke JT. What is new in preeclampsia?: best articles from the past year. Obstet Gynecol. 2013 Mar;121(3):682–3. [PMID: 23635633]
Acute fatty liver of pregnancy is a disorder limited to the gravid state. It occurs in the third trimester of pregnancy and involves acute hepatic failure. With improved recognition and immediate delivery, the mortality rate is now 7–23%. The disorder is usually seen after the 35th week of gestation and is more common in primigravidas and those with twins. The incidence is about 1:14,000 deliveries.
The cause of acute fatty liver of pregnancy is just now being elucidated, and it likely is the result of poor placental mitochondrial function. Many cases may be due to a homozygous fetal deficiency of long-chain acyl coenzyme A dehydrogenase (LCHAD).
Pathologic findings are unique to the disorder, with fatty engorgement of hepatocytes. Clinical onset is gradual, with flu-like symptoms that progress to the development of abdominal pain, jaundice, encephalopathy, disseminated intravascular coagulation, and death. On examination, the patient shows signs of hepatic failure.
Laboratory findings include marked elevation of alkaline phosphatase but only moderate elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Prothrombin time and bilirubin are also elevated. The white blood cell count is elevated, and the platelet count is depressed. Hypoglycemia may be extreme.
The differential diagnosis is that of fulminant hepatitis. However, liver aminotransferases for fulminant hepatitis are higher (> 1000 units/mL) than those for acute fatty liver of pregnancy (usually 500–1000 units/mL). It is also important to review the appropriate history and perform the appropriate tests for toxins that cause liver failure. Preeclampsia may involve the liver but typically does not cause jaundice. The elevations in liver function tests in patients with preeclampsia usually do not reach the levels seen in patients with acute fatty liver of pregnancy.
Diagnosis of acute fatty liver of pregnancy mandates immediate delivery. Supportive care during labor includes administration of glucose, platelets, and fresh frozen plasma as needed. Vaginal delivery is preferred. Resolution of encephalopathy occurs over days, and supportive care with a low-protein diet is needed.
Recurrence rates for this liver disorder are unclear but probably increased in families with proven LCHAD deficiency. Most authorities advise against subsequent pregnancy, but there have been reported cases of successful outcomes in later pregnancies.
Pan C et al. Pregnancy-related liver diseases. Clin Liver Dis. 2011 Feb;15(1):199–208. [PMID: 21112001]
ESSENTIALS OF DIAGNOSIS
Preterm regular uterine contractions approximately 5 minutes apart.
Cervical dilatation, effacement, or both.
Preterm birth is defined as delivery prior to 37 weeks gestation, and spontaneous preterm labor with or without premature rupture of the fetal membranes is responsible for at least two-thirds of all preterm births. Prematurity is the largest single contributor to infant mortality. Recognized risk factors for spontaneous preterm labor include a past history of spontaneous preterm delivery, premature rupture of the membranes, multiple gestation, black race, intrauterine infections, müllerian anomalies, smoking, substance abuse, bacterial vaginosis, and certain socioeconomic conditions (such as limited access to prenatal care). It has also been consistently demonstrated that women with a shortened cervical length as measured by transvaginal ultrasound in the midtrimester are at increased risk for spontaneous preterm delivery.
In women with regular uterine contractions and cervical change, the diagnosis of preterm labor is straightforward. However, symptoms such as pelvic pressure, cramping, or vaginal discharge may be the first complaints in high-risk patients who later develop preterm labor. Because these complaints may be vague and irregular uterine contractions are common, distinguishing which patients merit further evaluation can be problematic. In some cases, this distinction can be facilitated by the use of fetal fibronectin measurement in cervicovaginal specimens. This test is most useful when it is negative (< 50 ng/mL), since the negative predictive value for delivery within 7–14 days is 93–97%. A negative test, therefore, usually means the patient can be reassured and discharged home. Because of its low sensitivity, however, fetal fibronectin is not recommended as a screening test in asymptomatic women.
Patients must be educated to identify symptoms associated with preterm labor to avoid unnecessary delay in their evaluation. In patients who are believed to be at increased risk for preterm delivery, limited activity and bed rest continue to be recommended frequently despite the fact that randomized trials have failed to demonstrate improved outcomes in women placed on activity restriction. In addition, and paradoxically, such recommendations may place a woman at an increased risk to deliver preterm.
In pregnancies between 24 and 34 weeks gestation where preterm birth is anticipated, a single short course of corticosteroids should be administered to promote fetal lung maturity. Such therapy has been demonstrated to reduce the frequency of respiratory distress syndrome, intracranial hemorrhage, and even death in preterm infants. Betamethasone, 12 mg intramuscularly repeated once 24 hours later, or dexamethasone, 6 mg intramuscularly repeated every 12 hours for four doses, both cross the placenta and are the preferred treatments in this setting. Repeat courses are not recommended. Although antibiotics have not been proven to forestall delivery, women in preterm labor should receive antimicrobial prophylaxis against group B streptococcus (see above).
Numerous pharmacologic agents—tocolytics—have been given in an attempt to forestall preterm birth, although none are completely effective, and there is no evidence that such therapy directly improves neonatal outcomes. Administering tocolytic agents, however, remains a reasonable approach to the initial management of preterm labor and may provide sufficient prolongation of pregnancy to administer a course of corticosteroids and (if appropriate) transport the patient to a facility better equipped to care for preterm infants. Maintenance therapy (continuation of treatment beyond 48 hours) is not effective at preventing preterm birth and is not recommended. Likewise, despite the finding that preterm labor is associated with intrauterine infection in certain cases, there is no evidence that antibiotics forestall delivery in women with preterm labor and intact membranes.
Magnesium sulfate is commonly used, and there is evidence that it may also be protective against cerebral palsy in infants whose mothers were receiving magnesium infusions at time of birth. Magnesium sulfate is given intravenously as a 4- to 6-g bolus followed by a continuous infusion of 2 g/h. Magnesium levels are not typically checked but should be monitored if there is any concern for toxicity. Magnesium sulfate is entirely cleared by the kidney and must, therefore, be used with caution in women with any degree of renal insufficiency.
Beta-adrenergic drugs such as terbutaline have also been used. Terbutaline can be given as an intravenous infusion starting at 2.5 mcg/min or as a subcutaneous injection starting at 250 mcg given every 30 minutes. Oral terbutaline is no longer recommended because of the lack of proven efficacy and concerns about maternal safety. Serious maternal side effects have been reported with the use of terbutaline and include tachycardia, pulmonary edema, arrhythmias, metabolic derangements (such as hyperglycemia and hypokalemia), and even death. Pulmonary edema occurs with increased frequency with concomitant administration of corticosteroids, large volume intravenous fluid infusion, maternal sepsis, or prolonged tocolysis. Because of these safety concerns, the US Food and Drug Administration issued a warning recommendation that terbutaline be administered exclusively in a hospital setting and discontinued after 48–72 hours of treatment.
Nifedipine, 20 mg orally every 6 hours, and indomethacin, 50 mg orally once then 25 mg orally every 6 hours up to 48 hours, have also been used with limited success. Nifedipine should not be given in conjunction with magnesium sulfate.
Before attempts are made to prevent preterm delivery with tocolytic agents, the patient should be assessed for conditions in which delivery would be indicated. Severe preeclampsia, lethal fetal anomalies, placental abruption, and intrauterine infection are all examples of indications for preterm delivery. In such cases, attempts to forestall delivery would be inappropriate.
Strategies aimed at preventing preterm birth in high-risk women—principally those with a history of preterm birth or a shortened cervix (or both)—have focused on the administration of progesterone or progesterone compounds. Prospective randomized controlled trials have demonstrated reductions in rates of preterm birth in high-risk women with singleton pregnancies who received progesterone supplementation, although the optimal preparation, dose, and route of administration (intramuscular injection versus vaginal suppository) are unclear. Further, progesterone therapy has not been proven to be effective in nulliparous women who are noted to have a shortened cervix by transvaginal ultrasound, and universal screening of cervical length is controversial.
There is also evidence that women with a previous spontaneous preterm birth and a shortened cervix (< 25 mm before 24 weeks gestation) may benefit from placement of a cervical cerclage. The use of cervical cerclage in conjunction with progesterone supplementation has not been adequately studied. In twin pregnancies, however, neither progesterone administration nor cervical cerclage placement has been effective at prolonging pregnancy, suggesting that the mechanism for preterm birth may be different in multiple gestations.
• Symptoms of increased pelvic pressure or cramping in high-risk patients.
• Regular uterine contractions.
• Rupture of membranes.
• Vaginal bleeding.
• Cervical dilation of ≥ 2 cm prior to 34 weeks gestation.
• Contractions that cause cervical change.
• Rupture of membranes.
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 127: Management of preterm labor. Obstet Gynecol. 2012 Jun;119(6):1308–17. [PMID: 22617615]
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 130: Prediction and prevention of preterm birth. Obstet Gynecol. 2012 Oct;120(4):964–73. [PMID: 22996126]
Berghella V et al. Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth: a meta-analysis. Obstet Gynecol. 2011 Mar;117(3): 663–71. [PMID: 21446209]
Grobman WA et al. Activity restriction among women with a short cervix. Obstet Gynecol. 2013 Jun;121(6):1181–6. [PMID: 23812450]
Grobman WA et al. 17 alpha-hydroxyprogesterone caproate to prevent prematurity in nulliparas with cervical length less than 30 mm. Am J Obstet Gynecol. 2012 Nov;207(5):390.e1–8. [PMID: 23010094]
Hassan SS et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol. 2011 Jul;38(1):18–31. [PMID: 21472815]
Five to 10 percent of women have vaginal bleeding in late pregnancy. The clinician must distinguish between placental causes (placenta previa, placental abruption, vasa previa) and nonplacental causes (labor, infection, disorders of the lower genital tract, systemic disease). The approach to bleeding in late pregnancy generally should be conservative and expectant unless fetal distress or excessive maternal hemorrhage occurs.
The patient should be hospitalized and placed on bed rest. Initially, continuous fetal monitoring is indicated to assess for fetal distress. CBC platelets, and prothrombin time (INR) should be obtained and repeated serially if the bleeding continues. If the hemorrhage is significant, the need for blood replacement should be anticipated and two to four units of red cells typed and cross-matched, and repeat CBC and coagulation studies ordered as clinically indicated. Ultrasound examination should be performed to determine placental location. Digital pelvic examinations are done only after ultrasound examination has ruled out placenta previa.
Placenta previa occurs when the placenta implants over the internal cervical os. Risk factors for this condition include previous cesarean delivery, increasing maternal age, multiparity, and smoking. If the diagnosis is initially made in the first or second trimester, the ultrasound should be repeated in the third trimester. Persistence of placenta previa at this point is an indication for cesarean as the route of delivery. Painless vaginal bleeding is the characteristic symptom in placenta previa and can range from light spotting to profuse hemorrhage. Hospitalization for extended evaluation is the appropriate initial management approach. For pregnancies that have reached 37 weeks gestation or beyond with continued bleeding, delivery is generally indicated. Pregnancies at 36 weeks or earlier are candidates for expectant management provided the bleeding is not prodigious, and a subset of these women can be discharged if the bleeding and contractions completely subside.
Placenta accreta is the general term used to describe an abnormally adherent placenta that has invaded into or beyond the endometrium. Invasion extending into the myometrium is formally termed “placenta increta” and invasion beyond the uterine serosa, “placenta percreta.” Placenta accreta most commonly occurs in association with placenta previa in women who have had one more previous cesarean deliveries. After delivery of the infant, the placenta does not separate normally. The bleeding that results can be torrential, and emergency hysterectomy is usually required to stop the hemorrhage. Because of the considerable increase in both maternal morbidity and mortality associated with this condition, careful preoperative planning is imperative when the diagnosis is suspected antenatally. Ultrasound findings such as intraplacental lacunae, bridging vessels into the bladder, and loss of the retroplacental clear space suggest placental invasion in women who have placenta previa. Ideally, delivery planning should involve a multidisciplinary team, and the surgery should take place at an institution with appropriate personnel and a blood bank equipped to handle patients requiring massive transfusion.
Placental abruption is the premature separation of the placenta from its implantation site before delivery. Hypertension is a known risk factor for abruption. Other risk factors include multiparity, cocaine use, smoking, previous abruption, and thrombophilias. Classic symptoms are vaginal bleeding, uterine tenderness, and frequent contractions, but the clinical presentation is highly variable. Profound coagulopathy and acute hypovolemia from blood loss can occur and are more likely with an abruption severe enough to kill the fetus. Ultrasound may be helpful to exclude placenta previa, but failure to identify a retroplacental clot does not exclude abruption. In most cases, abruption is an indication for immediate delivery because of the high risk of fetal death.
American College of Obstetricians and Gynecologists. Committee Opinion No. 529: Placenta accreta. Obstet Gynecol. 2012 Jul;120(1):207–11. [PMID: 22914422]
Eller AG et al. Maternal morbidity in cases of placenta accreta managed by a multidisciplinary care team compared with standard obstetric care. Obstet Gynecol. 2011 Feb;117(2 Pt 1):331–7. [PMID: 21309195]
Postpartum mastitis occurs sporadically in nursing mothers, usually with symptom onset after discharge from the hospital, or it may occur in epidemic form in the hospital. Staphylococcus aureus is usually the causative agent. Inflammation is generally unilateral, and women nursing for the first time are more often affected. Rarely, inflammatory carcinoma of the breast can be mistaken for puerperal mastitis.
Mastitis frequently begins within 3 months after delivery and may start with an engorged breast and a sore or fissured nipple. Cellulitis is usually obvious in the affected area of breast with redness, tenderness, and local warmth. Fever and chills are common complaints as well. Treatment consists of antibiotics effective against penicillin-resistant staphylococci (dicloxacillin 500 mg orally every 6 hours or a cephalosporin for 10–14 days) and regular emptying of the breast by nursing or by using a mechanical suction device. Although nursing of the infected breast is safe for the infant, local inflammation of the nipple may complicate latching. Failure to respond to usual antibiotics within 3 days may represent an organizing abscess or infection with a resistant organism. When the causative organism is methicillin-resistant S aureus (MRSA), the risk for abscess formation is increased when compared with infection caused by nonresistant staphylococcal species. If an abscess is suspected, ultrasound of the breast can help confirm the diagnosis. In these cases, aspiration or surgical evacuation is usually required.
Dixon JM et al. Treatment of breast infection. BMJ. 2011 Feb 11;342:d396. [PMID: 21317199]
Lee IW et al. Puerperal mastitis requiring hospitalization during a nine-year period. Am J Obstet Gynecol. 2010 Oct;203(4):332.e1–6. [PMID: 20599181]
ESSENTIALS OF DIAGNOSIS
Fever not attributable to another source.
Foul smelling vaginal discharge.
Tachycardia in the mother, fetus, or both.
Pelvic infections are relatively common problems encountered during the peripartum period. Uterine infections diagnosed during pregnancy are referred to as chorioamnionitis—a generalized infection of all of the contents of the gravid uterus. Uterine infection after delivery is often called endometritis or endomyometritis, but the term “metritis” is probably most accurate to emphasize that the infection extends throughout the uterine tissue. These infections are polymicrobial and are most commonly attributed to urogenital pathogens. Risk factors include cesarean delivery, prolonged labor, use of internal monitors, nulliparity, multiple pelvic examinations, prolonged rupture of membranes, and lower genital tract infections. Although maternal complications such as dysfunctional labor and postpartum hemorrhage are increased with clinical chorioamnionitis, the principal reason to initiate treatment is to prevent morbidity in the offspring. Neonatal complications such as sepsis, pneumonia, intraventricular hemorrhage, and cerebral palsy are increased in the setting of chorioamnionitis. Intrapartum initiation of antibiotics, however, significantly reduces neonatal morbidity.
Clinical chorioamnionitis and metritis are diagnosed by the presence of fever (≥ 38°C) in the absence of any other source and one or more of the following signs: maternal tachycardia, fetal tachycardia, foul-smelling lochia, and uterine tenderness. Cultures are typically not done because of the polymicrobial nature of the infection.
Treatment is empiric with broad-spectrum antibiotics that will cover gram-positive and gram-negative organisms if still pregnant and gram-negative organisms and anaerobes if postpartum. A common regimen for chorioamnionitis is ampicillin, 2 g intravenously every 6 hours, and gentamicin, 2 mg/kg intravenous load then 1.5 mg/kg intravenously every 8 hours. A common regimen for metritis is gentamicin, 2 mg/kg intravenous load then 1.5 mg/kg intravenously every 8 hours, and clindamycin, 900 mg intravenously every 8 hours. Antibiotics are stopped in the mother when she has been afebrile for 24 hours. No oral antibiotics are subsequently needed. Patients with metritis who do not respond in the first 24–48 hours may have enterococcus and require additional gram-positive coverage (such as ampicillin) to the regimen.
Martinelli P et al. Chorioamnionitis and prematurity: a critical review. J Matern Fetal Neonatal Med. 2012 Oct;25(Suppl 4): 29–31. [PMID: 22958008]
Normal pregnancy is characterized by an increase in maternal plasma volume of about 50% and in increase in red cell volume of about 25%. Because of these changes, the mean hemoglobin and hematocrit values are lower than in the nonpregnant state. Anemia in pregnancy is considered when the hemoglobin measurement is below 11 g/dL. Symptoms such as fatigue and dyspnea that would otherwise suggest the presence of anemia in nonpregnant women are common in pregnant women; therefore, periodic measurement of CBCs in pregnancy is essential so that anemia can be identified and treated.
The increased requirement for iron over the course of pregnancy is appreciable in order to support fetal growth and expansion of maternal blood volume. Dietary intake of iron is generally insufficient to meet this demand, and it is recommended that all pregnant women receive about 30 mg of elemental iron per day in the second and third trimesters. Oral iron therapy is commonly associated with gastrointestinal side effects, such as nausea and constipation, and these symptoms often contribute to noncompliance. If supplementation is inadequate, however, anemia often becomes evident by the third trimester of pregnancy. Because iron deficiency is by far the most common cause of anemia in pregnancy, treatment is usually empiric and consists of 60–100 mg of elemental iron per day and a diet containing iron-rich foods. Iron studies can confirm the diagnosis if necessary (see Chapter 13), and further evaluation should be considered in patients who do not respond to oral iron. Intermittent iron supplementation (eg, every other day) has been associated with fewer side effects and may be reasonable for women who cannot tolerate daily therapy.
Megaloblastic anemia in pregnancy is almost always caused by folic acid deficiency, since vitamin B12 deficiency is extremely uncommon in the childbearing years.
The diagnosis is made by finding macrocytic red cells and hypersegmented neutrophils on a blood smear (see Chapter 13). However, blood smears in pregnancy may be difficult to interpret, since they frequently show iron deficiency changes as well. With established folate deficiency, a supplemental dose of 1 mg/d and a diet with increased folic acid is generally sufficient to correct the anemia.
Women with sickle cell anemia are subject to serious complications in pregnancy. The anemia becomes more severe, and acute pain crises often occur more frequently. When compared with women who do not have hemoglobinopathies, women with hemoglobin SS are at increased risk for infections (especially pulmonary and urinary tract), thromboembolic events, pregnancy-related hypertension, transfusion, cesarean delivery, preterm birth, and fetal growth restriction. There also continues to be an increased rate of maternal mortality, despite an increased recognition of the high-risk nature of these pregnancies. Intensive medical treatment may improve the outcomes for both mother and fetus. Prophylactically transfusing packed red cells to lower the level of hemoglobin S and elevate the level of hemoglobin A is a controversial practice without clear benefit. Most women with sickle cell disease will not require iron supplementation, but folate requirements can be appreciable due to red cell turnover from hemolysis. Management decisions should be made in conjunction with a maternal fetal medicine specialist and a hematologist.
Genetic counseling should be offered to patients with sickle cell disease or sickle trait (hemoglobin AS). If the father is a carrier of the sickle cell gene (or his status is unknown), the parents may wish to undergo prenatal diagnosis to determine whether the fetus is affected.
Contraceptive counseling postpartum is important, although the safest and most effective method in women with sickle cell disease is unclear. Progestin-only compounds may be ideal because progesterone has long been recognized to help prevent pain crises in some women. Intrauterine devices carry a risk of infection and combination oral contraceptives are a concern because of the thrombogenic potential; these forms of contraception have not been adequately studied in these patients.
Women with hemoglobin SC disease are also at increased risk for complications, but the morbidity does not appear to be as great as in women with SS disease. Women with either SC or SS disease are managed similarly. Women with sickle cell trait alone usually have an uncomplicated pregnancy course except for an increased risk of urinary tract infection.
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 95: Anemia in pregnancy. Obstet Gynecol. 2008 Jul;112(1):201–7. [PMID: 18591330]
Howard J et al. The obstetric management of sickle cell disease. Best Pract Res Clin Obstet Gynaecol. 2012 Feb;26(1):25–36. [PMID: 22113135]
Lassi ZS et al. Folic acid supplementation during pregnancy for maternal health and pregnancy outcomes. Cochrane Database Syst Rev. 2013 Mar 28;3:CD006896. [PMID: 23543547]
Peña-Rosas JP et al. Intermittent oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2012 Jul 11;7:CD009997. [PMID: 22786531]
(See also Chapter 20.)
The antiphospholipid syndrome (APS) is characterized by the presence of specific autoantibodies in association with certain clinical conditions, most notably arterial and venous thrombosis and adverse pregnancy outcomes. Clinically, the diagnosis can be suspected after any of the following outcomes: an episode of thrombosis, three or more unexplained consecutive spontaneous abortions prior to 10 weeks gestation, one or more unexplained deaths of a morphologically normal fetus after 10 weeks gestation, or a preterm delivery at less than 34 weeks due to preeclampsia or placental insufficiency. In addition to these clinical features, laboratory criteria include the identification of at least one of the following antiphospholipid antibodies: the lupus anticoagulant, anticardiolipin antibodies, or anti-beta-2-glycoprotein I antibodies. The lupus anticoagulant cannot be directly assayed, but it is tested for in several different phospholipid-dependent clotting tests and is interpreted as either present or absent. Anticardiolipin antibodies may be detected with enzyme-linked immunosorbent assay (ELISA) testing but should only be considered diagnostic when the IgG or IgM isotypes are present in medium to high titer (40 GPL or MPL, respectively). Likewise, anti-beta-2-glycoprotein I antibodies are detected with ELISA but should only be considered positive when they are present in a titer that is greater than 99th percentile for a normal population. The diagnosis of APS requires two positive antiphospholipid antibody test results at least 12 weeks apart since transient positive results can occur.
Treatment for APS in pregnancy generally involves administration of a heparin compound and low-dose aspirin (81 mg). In women with recurrent pregnancy loss and APS, it has been demonstrated that unfractionated heparin and low-dose aspirin can reduce the risk for spontaneous abortion. Outside of the first trimester, heparin is generally continued through pregnancy and the early postpartum period for thromboprophylaxis. LMWH is also commonly used for this indication; however, it is not clear that LMWH has the same effect on reducing the risk of recurrent abortion as unfractionated heparin. Either prophylactic or therapeutic dosing strategies may be appropriate depending on the patient’s history and clinical risk factors. Infusions of intravenous immunoglobulin are of unclear benefit in these patients, and this treatment is not recommended.
ACOG Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 132: Antiphospholipid syndrome. Obstet Gynecol. 2012 Dec;120(6):1514–21. [PMID: 23168789]
Oku K et al. Pathophysiology of thrombosis and pregnancy morbidity in the antiphospholipid syndrome. Eur J Clin Invest. 2012 Oct;42(10):1126–35. [PMID: 22784367]
Ziakas PD et al. Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss: a systematic review and meta-analysis. Obstet Gynecol. 2010 Jun;115(6):1256–62. [PMID: 20502298]
Thyroid disease is relatively common in pregnancy, and in their overt states, both hypothyroidism and hyperthyroidism have been consistently associated with adverse pregnancy outcomes. Fortunately, these risks are mitigated by adequate treatment. It is essential to understand the gestational age-specific effects that pregnancy has on thyroid function tests, since these biochemical markers are required to make the diagnosis of thyroid dysfunction. Failure to recognize these physiologic alterations can result in misclassification or misdiagnosis. Women who have a history of a thyroid disorder or symptoms that suggest thyroid dysfunction should be screened with thyroid function tests. Screening asymptomatic pregnant women, however, is controversial and not currently recommended by the American College of Obstetricians and Gynecologists.
Overt hypothyroidism is defined by an elevated serum TSH level with a depressed FT4 level. The condition in pregnancy has consistently been associated with an increase in complications such as spontaneous abortion, preterm birth, preeclampsia, placental abruption, and impaired neuropsychological development in the offspring. The most common etiology is Hashimoto (autoimmune) thyroiditis. Many of the symptoms of hypothyroidism mimic those of normal pregnancy, making its clinical identification difficult. Initial treatment is empiric with levothyroxine started at 75–100 mcg/d. Thyroid function tests can be repeated at 4–6 weeks and the dose adjusted as necessary with the goal of normalizing the TSH level (preferably to a trimester-specific gestational reference range). An increase in the dose of levothyroxine may be required in the second and third trimesters.
Subclinical hypothyroidism is defined as an increased serum TSH and a normal FT4 level. Although some adverse pregnancy outcomes (such as miscarriage and preeclampsia) have been associated with subclinical hypothyroidism, these findings have been inconsistent in the literature. There remains insufficient data at this time to recommend screening for or treating subclinical hypothyroidism in pregnancy.
Overt hyperthyroidism, defined as excessive production of thyroxine with a depressed (usually undetectable) serum TSH level, is also associated with increased risks in pregnancy. Spontaneous abortion, preterm birth, preeclampsia, and maternal heart failure occur with increased frequency with untreated thyrotoxicosis. Thyroid storm, although rare, can be a life-threatening complication. Medical treatment of thyrotoxicosis is usually accomplished with the antithyroid drugs propylthiouracil or methimazole. Although teratogenicity has not been clearly established, in utero exposure to methimazole has been associated with aplasia cutis and choanal and esophageal atresia in the offspring of pregnancies so treated. Propylthiouracil is not believed to be teratogenic, but it has been associated with the rare complications of hepatotoxicity and agranulocytosis. Recommendations by the American Thyroid Association are to treat with propylthiouracil in the first trimester and convert to methimazole for the remainder of the pregnancy. The therapeutic target for the FT4 level is the upper limit of the normal reference range. The TSH levels generally stay suppressed even with adequate treatment. A beta-blocker can be used for such symptoms as palpitations or tremors. Fetal hypothyroidism or hyperthyroidism is uncommon but can occur with maternal Graves disease, which is the most common cause of hyperthyroidism in pregnancy. Radioiodine ablation is absolutely contraindicated in pregnancy because it may destroy the fetal thyroid as well.
Transient autoimmune thyroiditis can occur in the postpartum period and is evident within the first year after delivery. The first phase, occurring up to 4 months postpartum, is a hyperthyroid state. Over the next few months, there is a transition to a hypothyroid state, which may require treatment with levothyroxine. Spontaneous resolution to a euthyroid state within the first year is the expected course; however, some women remain hypothyroid beyond this time (see Chapter 26).
Budenhofer BK et al. Thyroid (dys-)function in normal and disturbed pregnancy. Arch Gynecol Obstet. 2013 Jan;287(1): 1–7. [PMID: 23104052]
Casey BM. Subclinical thyroid dysfunction during pregnancy. Clin Obstet Gynecol. 2011 Sep;54(3):493–8. [PMID: 21857180]
Stagnaro-Green A et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011 Oct;21(10):1081–125. [PMID: 21787128]
Stagnaro-Green A et al. Thyroid disorders in pregnancy. Nat Rev Endocrinol. 2012 Nov;8(11):650–8. [PMID: 23007317]
Normal pregnancy can be characterized as a state of increased insulin resistance that helps ensure a steady stream of glucose delivery to the developing fetus. Thus, both mild fasting hypoglycemia and postprandial hyperglycemia are physiologic. These metabolic changes are felt to be hormonally mediated with likely contributions from human placental lactogen, estrogen, and progesterone.
Gestational diabetes mellitus is abnormal glucose tolerance in pregnancy and is generally believed to be an exaggeration of the pregnancy-induced physiologic changes in carbohydrate metabolism. Alternatively, pregnancy may unmask an underlying propensity for glucose intolerance, which will be evident in the nonpregnant state at some future time if not in the immediate postpartum period. Indeed, at least 50% of women with gestational diabetes are diagnosed with overt diabetes at some point in their lifetime. During the pregnancy, the principal concern in women identified to have gestational diabetes is excessive fetal growth, which can result in increased maternal and perinatal morbidity. Shoulder dystocia occurs more frequently in infants of diabetic mothers because of fetal overgrowth and increased fat deposition on the shoulders. Cesarean delivery and preeclampsia are also significantly increased in women with diabetes, both gestational and overt.
All pregnant women should undergo screening for gestational diabetes, either by history, clinical risk factors, or (most commonly) laboratory screening tests. The diagnostic thresholds for glucose tolerance tests in pregnancy are not universally agreed upon, and importantly, adverse pregnancy outcomes appear to occur along a continuum of glucose intolerance even if the diagnosis of gestational diabetes is not formally assigned. A two-stage testing strategy is most commonly used in the United States, starting with a 50-g glucose test offered to all pregnant women at 24–28 weeks gestation. If this test is abnormal, the diagnostic test is a 100-g oral glucose tolerance test (Table 19–4). Women in whom gestational diabetes is diagnosed should undergo nutrition counseling, and insulin should be given to those with persistent fasting hyperglycemia. Insulin can be injected in a split dose mix of NPH and regular, administered twice daily. Insulin has long been regarded as the standard care for women who require medical management. Experience is increasing, however, with the use of oral hypoglycemic agents, such as glyburide and metformin. Randomized controlled trials comparing insulin to oral therapy have identified generally similar maternal and neonatal outcomes with either approach, although the long-term safety of oral agents has not been adequately studied in the women so treated or in their infants. Capillary blood glucose monitoring is checked four times per day, once fasting and three times after meals. Euglycemia is considered to be 60–90 mg/dL (3.3–5.0 mmol/L) while fasting and < 120 mg/dL (< 6.7 mmol/L) 2 hours postprandially. Intensive therapy with dietary modifications or insulin therapy, or both, has been demonstrated to decrease rates of macrosomia, shoulder dystocia, and preeclampsia. Because of the increased prevalence of overt diabetes in these women, they should be screened at 6–12 weeks postpartum with a fasting plasma glucose test or a 2-hour oral glucose tolerance test (75-g glucose load).
Table 19–4. Screening and diagnostic criteria for gestational diabetes mellitus.
Overt diabetes is diabetes mellitus that antedates the pregnancy. As in gestational diabetes, fetal overgrowth from inadequately controlled hyperglycemia remains a significant concern because of the increased maternal and perinatal morbidity that accompany macrosomia. Women with overt diabetes are subject to a number of other complications as well. Spontaneous abortions and third trimester stillbirths occur with increased frequency in these women. There is also at least a twofold to threefold increased risk for fetal malformations, as hyperglycemia during organogenesis is teratogenic. The most common malformations in offspring of diabetic women are cardiac, skeletal, and neural tube defects. For the mother, the likelihood of infections and pregnancy-related hypertension is increased.
Preconception counseling and evaluation in a diabetic woman is ideal to maximize the pregnancy outcomes. This provides an opportunity to optimize glycemic control and evaluate for evidence of end-organ damage. The initial evaluation of diabetic women should include a complete chemistry panel, HbA1c determination, 24-hour urine collection for total protein and creatinine clearance, funduscopic examination, and an ECG. Hypertension is common and may require treatment. Optimally, euglycemia should be established before conception and maintained during pregnancy with daily home glucose monitoring by the patient. There is an inverse relationship between glycemic control and the occurrence of fetal malformations, and women whose periconceptional glycosylated hemoglobin levels are at or near normal levels have rates of malformations that approach baseline. A well-planned dietary program is a key component, with an intake of 1800–2200 kcal/d divided into three meals and three snacks. Insulin is given subcutaneously in a split-dose regimen as described above for women with gestational diabetes. The use of continuous insulin pump therapy may be helpful for some patients.
Throughout the pregnancy, diabetic women should be seen every 2–3 weeks and more frequently depending on the clinical condition. Adjustments in the insulin regimen may be necessary as the pregnancy progresses. A specialized ultrasound is often performed around 20 weeks to detect fetal malformations. Symptoms and signs of infections should be evaluated and promptly treated. In the third trimester, fetal surveillance is indicated, and women with diabetes should receive serial antenatal testing (usually in the form of a nonstress test or biophysical profile). The timing of delivery is dictated by the quality of diabetic control, the presence or absence of medical complications, and fetal status. The goal is to reach 39 weeks (38 completed weeks) and then proceed with delivery. Confirmation of lung maturity may be appropriate if preterm delivery is contemplated.
ACOG Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 137: Gestational diabetes mellitus. Obstet Gynecol. 2013 Aug;122(2 Pt 1):406–16. [PMID: 23969827]
Ali S et al. Diabetes in pregnancy: health risks and management. Postgrad Med J. 2011 Jun;87(1028):417–27. [PMID: 21368321]
Ringholm L et al. Managing type 1 diabetes mellitus in pregnancy—from planning to breastfeeding. Nat Rev Endocrinol. 2012 Nov;8(11):659–67. [PMID: 22965164]
Vandorsten JP et al. NIH consensus development conference: diagnosing gestational diabetes mellitus. NIH Consens State Sci Statements. 2013 Mar 6;29(1):1–31. [PMID: 23748438]
Wahabi HA et al. Pre-pregnancy care for women with pre-gestational diabetes mellitus: a systematic review and meta-analysis. BMC Public Health. 2012 Sep 17;12:792. [PMID: 22978747]
Chronic hypertension is estimated to complicate up to 5% of pregnancies. To establish this diagnosis, hypertension should antedate the pregnancy or be evident before 20 weeks gestation to differentiate it from pregnancy-related hypertension. This distinction can be problematic when the initial presentation is after 20 weeks, but chronic hypertension is confirmed if the blood pressure remains elevated beyond 12 weeks postpartum. Risk factors for chronic hypertension include older maternal age, African American race, and obesity. While essential hypertension is by far the most common cause, secondary causes should be sought when clinically indicated.
Women with chronic hypertension are at increased risk for adverse maternal and perinatal outcomes. Superimposed preeclampsia develops in up to 20% of women with mild hypertension, but the risk increases up to 50% when there is severe baseline hypertension (≥ 160/110 mm Hg) and may be even higher when there is evidence of end-organ damage. When preeclampsia is superimposed on chronic hypertension, there is a tendency for it to occur at an earlier gestational age, be more severe, and impair fetal growth. Women with chronic hypertension are also at increased risk for placental abruption, preterm birth, and perinatal mortality.
Ideally, women with chronic hypertension should undergo an evaluation prior to conception to detect end-organ damage and assess the need for enhanced antihypertensive therapy (see Table 11–1). The specific tests ordered may vary depending on the severity of the hypertensive disorder, but an evaluation of renal and cardiac function is appropriate.
If the woman is not known to have chronic hypertension, then initiation of antihypertensive therapy in pregnant women is indicated only if the blood pressure is sustained at or above 150/100 mm Hg or if there is evidence of end-organ damage. Treatment of hypertension has not been demonstrated to improve pregnancy outcomes, but it is indicated in women with significant hypertension for long-term maternal cardiovascular health. For initiation of treatment in pregnancy, methyldopa has the longest record of safety at a starting dosage of 250 mg orally two to three times daily. Therapy with beta-blockers or calcium channel blockers is also acceptable (see Tables 11–6, 11–8). Care must be taken not to excessively reduce the blood pressure, as this may decrease uteroplacental perfusion. The goal is a modest reduction in blood pressure and avoidance of severe hypertension.
If a woman with mild chronic hypertension is stable on a medical regimen when she becomes pregnant, it is usually appropriate to continue this therapy, although the benefits of doing so are not well-established. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, however, are contraindicated in all trimesters of pregnancy. In addition to causing fetal hypocalvaria and acute kidney injury with exposure in the second and third trimesters, it is now recognized that these medications are teratogenic in the first trimester. Diuretics, although not typically initiated in pregnancy, may be continued in patients who are taking them when they become pregnant.
When there is sustained severe hypertension despite multiple medications or significant end-organ damage from hypertensive disease, pregnancy is not likely to be tolerated well. In these situations, therapeutic abortion may be appropriate. If the pregnancy is continued, the woman must be counseled that the maternal and perinatal risks are appreciable, and complications such as superimposed preeclampsia and fetal growth restriction should be anticipated.
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 125: Chronic hypertension in pregnancy. Obstet Gynecol. 2012 Feb;119(2 Pt 1):396–407. [PMID: 22270315]
Ames M et al. Ambulatory management of chronic hypertension in pregnancy. Clin Obstet Gynecol. 2012 Sep;55(3):744–55. [PMID: 22828107]
Palma-Reis I et al. Renal disease and hypertension in pregnancy. Clin Med. 2013 Feb;13(1):57–62. [PMID: 23472497]
Seely EW et al. Chronic hypertension in pregnancy. N Engl J Med. 2011 Aug 4;365(5):439–46. [PMID: 21812673]
Normal pregnancy physiology is characterized by cardiovascular adaptations in the mother. Cardiac output increases markedly as a result of both augmented stroke volume and an increase in the resting heart rate, and the maternal blood volume expands by up to 50%. These changes may not be tolerated well in women with functional or structural abnormalities of the heart. Thus, although only a small number of pregnancies are complicated by cardiac disease, these contribute disproportionately to overall rates of maternal morbidity and mortality. Most cardiac disease in women of childbearing age in the United States is caused by congenital heart disease. Ischemic heart disease, however, is being seen more commonly in pregnant women due to increasing rates of comorbid conditions, such as diabetes mellitus, hypertension, and obesity.
For practical purposes, the best single measurement of cardiopulmonary status is defined by the New York Heart Association Functional Classification. Most pregnant women with cardiac disease have class I or II functional disability, and although good outcomes are generally anticipated in this group, complications such as preeclampsia, preterm birth, and low birth weight appear to occur with increased frequency. Women with more severe disability (class III or IV) are rare in contemporary obstetrics; however, the maternal mortality is markedly increased in this setting and is usually the result of heart failure. Because of these risks, therapeutic abortion for maternal health should be considered in women who are severely disabled from cardiac disease. Specific conditions that have been associated with a particularly high risk for maternal death include Eisenmenger syndrome, primary pulmonary hypertension, Marfan syndrome with aortic root dilatation, and severe aortic or mitral stenosis. In general, these conditions should be considered contraindications to pregnancy.
Pregnant women with cardiac disease are best treated by a team of practitioners with experience in caring for such patients. Heart failure is the most common cardiovascular complication associated with heart disease in pregnancy, and adverse maternal and fetal outcomes are increased when heart failure occurs. Symptoms of volume overload should therefore be evaluated and treated promptly. Labor management may differ depending on the specific cardiac lesion, but cesarean delivery is generally reserved for obstetric indications. The early postpartum period is a critical time for fluid management. Patients who are predisposed to heart failure should be monitored closely during the puerperium.
Infective endocarditis prophylaxis is not recommended for a vaginal or cesarean delivery in the absence of infection, except in the very small subset of patients at highest risk for adverse outcomes from endocarditis. The women at highest risk include those with cyanotic heart disease, prosthetic valves, or both. If infection is present, such as chorioamnionitis, the underlying infection should be treated with the usual regimen and additional agents are not needed specifically for endocarditis prophylaxis. Prophylaxis, if required, should be given intravenously (see Table 33–6).
Ruys TP et al. Heart failure in pregnant women with cardiac disease: data from the ROPAC. Heart. 2014 Feb;100(3):231–8. [PMID: 24293523]
Simpson LL. Maternal cardiac disease: update for the clinician. Obstet Gynecol. 2012 Feb;119(2 Pt 1):345–59. [PMID: 22270287]
(See also Chapter 9.)
Asthma is one of the most common medical conditions encountered in pregnancy. Women with mild to moderate asthma can generally expect excellent pregnancy outcomes, but severe or poorly controlled asthma has been associated with a number of pregnancy complications, including preterm birth, small-for-gestational-age infants, and preeclampsia. The effects of pregnancy on asthma are likely minimal as asthma severity in the pregnancy has been reported to be similar to its severity during the year preceding the pregnancy. Strategies for treatment are similar to that in nonpregnant women. Patients should be educated about symptom management and avoidance of asthma triggers. Baseline pulmonary function tests can provide an objective assessment of lung function and may help the patient with self-monitoring of her asthma severity using a peak flow meter. As in nonpregnant women, treatment algorithms generally follow a step-wise approach, and commonly used medications, particularly those for mild to moderate asthma symptoms, are generally considered safe in pregnancy. Concerns about teratogenicity and medication effects on the fetus should be thoroughly discussed with the patient to decrease noncompliance rates. Inhaled beta-2-agonists are indicated for all asthma patients, and low to moderate dose inhaled corticosteroids are added for persistent symptoms when a rescue inhaler alone is inadequate. Systemic corticosteroid administration is reserved for severe exacerbations but should not be withheld, if indicated, irrespective of gestational age. The primary goals of management in pregnancy include minimizing symptoms and avoiding hypoxic episodes to the fetus.
Gregersen TL et al. Safety of bronchodilators and corticosteroids for asthma during pregnancy: what we know and what we need to do better. J Asthma Allergy. 2013 Nov 15;6:117–25. [PMID: 24259987]
McCallister JW. Asthma in pregnancy: management strategies. Curr Opin Pulm Med. 2013 Jan;19(1):13–7. [PMID: 23154712]
Murphy VE et al. A meta-analysis of adverse perinatal outcomes in women with asthma. BJOG. 2011 Oct;118(11):1314–23. [PMID: 21749633]
Epilepsy is one of the most common serious neurologic disorders in pregnant women. Many of the commonly used antiepileptic drugs are known human teratogens. Therefore, the principal objectives in managing pregnancy in epileptic women are achieving adequate control of seizures while minimizing exposure to medications that can cause congenital malformations. Certain women who are contemplating pregnancy and have been seizure-free for 2–5 years may be considered candidates for discontinuation of antiseizure medication prior to pregnancy. For those who continue to require treatment, however, therapy with one medication is preferred. Selecting a regimen should be based on the type of seizure disorder and the risks associated with each medication. Valproic acid should not be considered first-line therapy because it has consistently been associated with higher rates of fetal malformations than most other commonly used antiepileptic drugs, and there are data to suggest that it is also associated with impairments of cognitive development in the offspring. Phenytoin and carbamazepine are also older medications that are still used, and both have established patterns of associated fetal malformations. Concerns about teratogenicity have prompted increasing use of the newer antiepileptic drugs such as lamotrigine, topiramate, oxcarbazepine, and levetiracetam. Although the safety of these medications in pregnancy continues to be evaluated, experiences from ongoing registries and large, population-based studies suggest that in utero exposure to the newer antiepileptic drugs in the first trimester of pregnancy carries a lower risk of major malformations than older medications. Although it is recommended that pregnant women with epilepsy be given supplemental folic acid, it is unclear if supplemental folate decreases rates of fetal malformations in women taking anticonvulsant therapy.
Hern´ndez-Díaz S et al; North American AED Pregnancy Registry. Comparative safety of antiepileptic drugs during pregnancy. Neurology. 2012 May 22;78(21):1692–9. [PMID: 22551726]
Molgaard-Nielsen D et al. Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA. 2011 May 18;305(19):1996–2002. [PMID: 21586715]
Tomson T et al. Antiepileptic drug treatment in pregnancy: changes in drug disposition and their clinical implications. Epilepsia. 2013 Mar;54(3):405–14. [PMID: 23360413]
Vajda FJ et al. Teratogenicity of the newer antiepileptic drugs—the Australian experience. J Clin Neurosci. 2012 Jan; 19(1):57–9. [PMID: 22104350]
The urinary tract is especially vulnerable to infections during pregnancy because the altered secretions of steroid sex hormones and the pressure exerted by the gravid uterus on the ureters and bladder cause hypotonia and congestion and predispose to urinary stasis. Labor and delivery and urinary retention postpartum also may initiate or aggravate infection. Escherichia coli is the offending organism in over two-thirds of cases.
From 2% to 8% of pregnant women have asymptomatic bacteriuria, which some believe to be associated with an increased risk of preterm birth. It is estimated that pyelonephritis will develop in 20–40% of these women if untreated.
An evaluation for asymptomatic bacteriuria at the first prenatal visit is recommended for all pregnant women. If a urine culture is positive, treatment should be initiated. Nitrofurantoin (100 mg orally twice daily), ampicillin (250 mg orally four times daily), and cephalexin (250 mg orally four times daily) are acceptable medications for 4–7 days. Sulfonamides should be avoided in the third trimester because they may interfere with bilirubin binding and thus impose a risk of neonatal hyperbilirubinemia and kernicterus. Fluoroquinolones are also contraindicated because of their potential teratogenic effects on fetal cartilage and bone. Patients with recurrent bacteriuria should receive suppressive medication (once daily dosing of an appropriate antibiotic) for the remainder of the pregnancy. Acute pyelonephritis requires hospitalization for intravenous administration of antibiotics and crystalloids until the patient is afebrile; this is followed by a full course of oral antibiotics.
Widmer M et al. Duration of treatment for asymptomatic bacteriuria during pregnancy. Cochrane Database Syst Rev. 2011 Dec 7;(12):CD000491. [PMID: 22161364]
Group B streptococci frequently colonize the lower female genital tract, with an asymptomatic carriage rate in pregnancy of 10–30%. This rate depends on maternal age, gravidity, and geographic variation. Vaginal carriage is asymptomatic and intermittent, with spontaneous clearing in approximately 30% and recolonization in about 10% of women. Adverse perinatal outcomes associated with group B streptococcal colonization include urinary tract infection, intrauterine infection, premature rupture of membranes, preterm delivery, and postpartum metritis.
Women with postpartum metritis due to infection with group B streptococci, especially after cesarean section, develop fever, tachycardia, and abdominal pain, usually within 24 hours after delivery. Approximately 35% of these women are bacteremic.
Group B streptococcal infection is a common cause of neonatal sepsis. Transmission rates are high, yet the rate of neonatal sepsis is surprisingly low at < 1:1000 live births. Unfortunately, the mortality rate associated with early-onset disease can be as high as 20–30% in premature infants. In contrast, it is approximately 2–3% in those at term. Moreover, these infections can contribute markedly to chronic morbidity, including mental retardation and neurologic disabilities. Late-onset disease develops through contact with hospital nursery personnel. Up to 45% of these health care workers can carry the bacteria on their skin and transmit the infection to newborns.
CDC recommendations for screening and prophylaxis for group B streptococcal colonization are set forth above (see Essentials of Prenatal Care: Tests and Procedures).
Clifford V et al. Prevention of neonatal group B streptococcus disease in the 21st century. J Paediatr Child Health. 2012 Sep;48(9):808–15. [PMID: 22151082]
Ohlsson A et al. Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database Syst Rev. 2013 Jan 31;1:CD007467. [PMID: 23440815]
Verani JR et al; Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease—revised guidelines from CDC, 2010. MMWR Recomm Rep. 2010 Nov 19;59(RR-10):1–36. [PMID: 21088663]
Commonly known as chickenpox, varicella-zoster virus (VZV) infection has a fairly benign course when incurred during childhood but may result in serious illness in adults, particularly during pregnancy. Infection results in lifelong immunity. Approximately 95% of women born in the United States have VZV antibodies by the time they reach reproductive age. The incidence of VZV infection during pregnancy has been reported as up to 7:10,000.
The incubation period for this infection is 10–20 days. A primary infection follows and is characterized by a flu-like syndrome with malaise, fever, and development of a pruritic maculopapular rash on the trunk, which becomes vesicular and then crusts. Pregnant women are prone to the development of VZV pneumonia, often a fulminant infection sometimes requiring respiratory support. After primary infection, the virus becomes latent, ascending to dorsal root ganglia. Subsequent reactivation can occur as zoster, often under circumstances of immunocompromise, although this is rare during pregnancy.
Two types of fetal infection have been documented. The first is congenital VZV syndrome, which typically occurs in 0.4–2% of fetuses exposed to primary VZV infection during the first trimester. Anomalies include limb and digit abnormalities, microphthalmos, and microcephaly.
Infection during the second and third trimesters is less threatening. Maternal IgG crosses the placenta, protecting the fetus. The only infants at risk for severe infection are those born after maternal viremia but before development of maternal protective antibody. Maternal infection manifesting 5 days before or up to 2 days after delivery is the time period believed to be most hazardous for transmission to the fetus.
Diagnosis is commonly made on clinical grounds. Laboratory verification of recent infection is made most often by antibody detection techniques, including ELISA, fluorescent antibody, and hemagglutination inhibition. Serum obtained by cordocentesis may be tested for VZV IgM to document fetal infection.
Varicella-zoster immune globulin (VZIG) has been shown to prevent or modify the symptoms of infection. Treatment success depends on identification of susceptible women at or just following exposure. Women with a questionable or negative history of chickenpox should be checked for antibody, since the overwhelming majority will have been previously exposed. If the antibody is negative, VZIG (625 units intramuscularly) should ideally be given within 96 hours of exposure for greatest efficacy, but the CDC reports it can be given for up to 10 days. There are no known adverse effects of VZIG administration during pregnancy, although the incubation period for disease can be lengthened. Infants born within 5 days after onset of maternal infection should also receive VZIG (125 units).
Infected pregnant women should be closely observed and hospitalized at the earliest signs of pulmonary involvement. Intravenous acyclovir (10 mg/kg intravenously every 8 hours) is recommended in the treatment of VZV pneumonia.
Centers for Disease Control and Prevention (CDC). Updated recommendations for use of VariZIG—United States, 2013. MMWR Morb Mortal Wkly Rep. 2013 July19;62(28):574–6. [PMID: 23863705]
Lamont RF et al. Varicella-zoster virus (chickenpox) infection in pregnancy. BJOG. 2011 Sep;118(10):1155–62. [PMID: 21585641]
The diagnosis of tuberculosis in pregnancy is made by history taking, physical examination, and testing, with special attention to women in high-risk groups. Women at high risk include those who are from endemic areas, those infected with HIV, drug users, health care workers, and close contacts of people with tuberculosis. Chest radiographs should not be obtained as a routine screening measure in pregnancy but should be used only in patients with a positive test or with suggestive findings in the history and physical examination. Abdominal shielding must be used if a chest radiograph is obtained. Both tuberculin skin testing and interferon gamma release assays are acceptable tests in pregnancy.
Decisions on treatment depend on whether the patient has active disease or is at high risk for progression to active disease. Pregnant women with latent disease not at high risk for disease progression can receive treatment postpartum, which does not preclude breastfeeding. The concentration of medication in breast milk is neither toxic nor adequate for treatment of the newborn. Treatment is with isoniazid and ethambutol or isoniazid and rifampin (see Chapters 9 and 33). Because isoniazid therapy may result in vitamin B6 deficiency, a supplement of 50 mg/d of vitamin B6 should be given simultaneously. There is concern that isoniazid, particularly in pregnant women, can cause hepatitis. Liver function tests should be performed regularly in pregnant women who receive treatment. Streptomycin, ethionamide, and most other antituberculous drugs should be avoided in pregnancy. If adequately treated, tuberculosis in pregnancy has an excellent prognosis.
Mathad JS et al. Tuberculosis in pregnant and postpartum women: epidemiology, management, and research gaps. Clin Infect Dis. 2012 Dec;55(11):1532–49. [PMID: 22942202]
Taylor AW et al. Pregnancy outcomes in HIV-infected women receiving long-term isoniazid prophylaxis for tuberculosis and antiretroviral therapy. Infect Dis Obstet Gynecol. 2013;2013:195637. [PMID: 23533318]
Heterosexual acquisition and injection drug use are the principal identified modes of HIV infection in women. Asymptomatic infection is associated with a normal pregnancy rate and no increased risk of adverse pregnancy outcomes. There is no evidence that pregnancy causes AIDS progression.
Previously, two-thirds of HIV-positive neonates acquired their infection close to, or during, the time of delivery. Routine HIV screening in pregnancy, including the use of rapid HIV tests in Labor and Delivery units, and the use of antiretroviral drugs has markedly reduced this transmission risk to approximately 2%. In an HIV-positive pregnant woman, a CD4 count, plasma RNA level, and resistance testing (if virus is detectable) should be obtained at the first prenatal visit. Prior or current antiretroviral use should be reviewed. A woman already taking and tolerating an acceptable antiretroviral regimen does not have to discontinue it in the first trimester. Patients should also be tested for hepatitis C, tuberculosis, toxoplasmosis, and cytomegalovirus.
Women not taking medication should be offered antiretroviral therapy with three drugs (commonly two nucleoside analogues and one protease inhibitor, including zidovudine whenever possible) after counseling regarding the potential impact of therapy on both mother and fetus. Antiretroviral therapy should be offered regardless of viral load and CD4 count, and it should be started in the secondtrimester unless there is a maternal indication to start earlier. The majority of drugs used to treat HIV/AIDS have thus far proven to be safe in pregnancy with an acceptable risk/benefit ratio. Efavirenz has been clearly linked with anomalies (myelomeningocele) and should not be used in the first trimester of pregnancy. However, efavirenz does not need to be discontinued if a pregnant patient presents for obstetrical care already taking the drug. Standard of care also includes administration of intravenous zidovudine prior to cesarean delivery and during labor in women whose viral load near delivery is ≥ 400 copies/mL or unknown. Antiretroviral therapy should also be continued in labor.
The use of prophylactic elective cesarean section at 38 weeks (before the onset of labor or rupture of the membranes) to prevent vertical transmission of HIV infection from mother to fetus has been shown to further reduce the transmission rate. In patients with a viral load of < 1000 copies/mL, there may be no additional benefit of cesarean delivery, and those women can be offered a vaginal delivery. Amniotomy should not be performed, and internal monitors, particularly the fetal scalp electrode, should be avoided. HIV-infected women should be advised not to breastfeed their infants.
The Public Health Task Force provides guidelines for the management of HIV/AIDS in pregnancy that are regularly updated and available at http://www.aidsinfo.nih.gov/. In addition, there is the National Perinatal HIV Hotline, which provides free consultation regarding perinatal HIV care (1-888-448-8765).
Lazenby GB. Opportunistic infections in women with HIV AIDS. Clin Obstet Gynecol. 2012 Dec;55(4):927–37. [PMID: 23090461]
U.S. Department of Health & Human Services Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1 infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. 2012 July 14:1–207.http://aidsinfo.nih.gov/ContentFiles/lvguidelines/PerinatalGL.pdf
There are an estimated 350 million chronic carriers of hepatitis B virus worldwide. Among these people, there is an increased incidence of chronic active hepatitis, cirrhosis, and hepatocellular carcinoma. In the United States, 1.4 million people are infected, with the highest rate among Asian Americans. All pregnant women should be screened for HBsAg. Transmission of the virus to the baby after delivery is likely if both surface antigen and e antigen are positive. Vertical transmission can be blocked by the immediate postdelivery administration to the newborn of hepatitis B immunoglobulin and hepatitis B vaccine intramuscularly. The vaccine dose is repeated at 1 and 6 months of age. Successful, but limited, experience has also been reported with lamivudine during the third trimester to prevent vertical transmission of hepatitis B in mothers with high HBV viral loads. Pregnant women with chronic hepatitis B should have liver function tests during the pregnancy. Hepatitis B infection is not a contraindication to breastfeeding.
Hepatitis C virus infection is the most common chronic blood-borne infection in the United States. Risk factors for transmission include blood transfusion, injection drug use, employment in patient care or clinical laboratory work, exposure to a sex partner or household member who has had a history of hepatitis, exposure to multiple sex partners, and low socioeconomic level. The average rate of hepatitis C virus (HCV) infection among infants born to HCV-positive, HIV-negative women is 5–6%. However, the average infection rate increases to 14% when mothers are coinfected with HCV and HIV. The principal factor associated with transmission is the presence of HCV RNA in the mother at the time of birth.
Esposti SD et al. Hepatitis B in pregnancy: challenges and treatment. Gastroenterol Clin North Am. 2011 Jun;40(2):355–72. [PMID: 21601784]
Infection of the lower genital tract by herpes simplex virus type 2 (HSV-2) (see also Chapter 6) is a common STD with potentially serious consequences to pregnant women and their newborn infants. Although up to 20% of women in an obstetric practice may have antibodies to HSV-2, a history of the infection is unreliable and the incidence of neonatal infection is low (10–60/100,000 live births). Most infected neonates are born to women with no history, symptoms, or signs of infection.
Women who have had primary herpes infection late in pregnancy are at high risk for shedding virus at delivery. Some authors suggest use of prophylactic acyclovir, 400 mg orally three times daily, to decrease the likelihood of active lesions at the time of labor and delivery.
Women with a history of recurrent genital herpes have a lower neonatal attack rate than women infected during the pregnancy, but they should still be monitored with clinical observation and culture of any suspicious lesions. Since asymptomatic viral shedding is not predictable by antepartum cultures, current recommendations do not include routine cultures in individuals with a history of herpes without active disease. However, when labor begins, vulvar and cervical inspection should be performed. Cesarean delivery is indicated at the time of labor if there are prodromal symptoms, active genital lesions, or a positive cervical culture obtained within the preceding week.
For treatment, see Chapter 32. The use of acyclovir in pregnancy is acceptable, and prophylaxis starting at 36 weeks gestation has been shown to decrease the number of cesarean sections performed for active disease.
Jaiyeoba O et al. Preventing neonatal transmission of herpes simplex virus. Clin Obstet Gynecol. 2012 Jun;55(2):510–20. [PMID: 22510634]
Pinninti SG et al. Maternal and neonatal herpes simplex virus infections. Am J Perinatol. 2013 Feb;30(2):113–9. [PMID: 23303485]
These STDs have significant consequences for mother and child. Untreated syphilis in pregnancy can cause late abortion, stillbirth, transplacental infection, and congenital syphilis. Gonorrhea can produce large-joint arthritis by hematogenous spread as well as ophthalmia neonatorum. Maternal chlamydial infections are largely asymptomatic but are manifested in the newborn by inclusion conjunctivitis and, at age 2–4 months, by pneumonia. The diagnosis of each can be reliably made by appropriate laboratory tests. All women should be tested for syphilis and C trachomatis as part of their routine prenatal care. Repeat testing is dependent on risk factors, prevalence, and state laws. Women at risk should be tested for gonorrhea. The sexual partners of women with STDs should be identified and treated also if possible; the local health department can assist with this process.
Hawkes SJ et al. Early antenatal care: does it make a difference to outcomes of pregnancy associated with syphilis? A systematic review and meta-analysis. PLoS One. 2013;8(2):e56713. [PMID: 23468875]
Workowski KA et al; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec 17;59(RR-12):1–110. [PMID: 21160459]
Although purely elective surgery should be avoided during pregnancy, women who undergo surgical procedures for an urgent or emergent indication during pregnancy do not appear to be at increased risk for adverse outcomes. Obstetric complications, when they occur, are more likely to be associated with the underlying maternal illness. Recommendations have held that the optimal time for semi-elective surgery is the second trimester to avoid exposure to anesthesia in the first trimester and the enlarged uterus in the third. Importantly, however, there is no convincing evidence that general anesthesia induces malformations or increases the risk for abortion.
Cholelithiasis is common in pregnancy as physiologic changes such as increased cholesterol production and incomplete gallbladder emptying predispose to gallstone formation. The diagnosis is usually suspected based on classic symptoms of nausea, vomiting, and right upper quadrant pain, usually after meals, and is confirmed with right upper quadrant ultrasound. Symptomatic cholelithiasis without cholecystitis is usually managed conservatively, but recurrent symptoms are common. Cholecystitis results from obstruction of the cystic duct and often is accompanied by bacterial infection. Medical management with antibiotics is reasonable in selected cases, but definitive treatment with cholecystectomy will help prevent complications such as gallbladder perforation and pancreatitis. Cholecystectomy has successfully been performed in all trimesters of pregnancy and should not be withheld based on the stage of pregnancy if clinically indicated. Laparoscopy is preferred in the first half of pregnancy but becomes technically difficult in the last trimester due to the enlarged uterus and cephalad displacement of abdominal contents.
Obstruction of the common bile duct can lead to cholangitis requiring surgical removal of gallstones and establishment of biliary drainage. Magnetic resonance cholangiopancreatography (MRCP) can be of use in patients with common bile duct dilatation in whom the ultrasound results are equivocal. MRCP can provide detailed evaluation of the entire biliary system and the pancreas while avoiding ionizing radiation. When necessary, however, endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic retrograde sphincterotomy can be performed safely in pregnant women if precautions are taken to minimize fetal exposure to radiation. There does, however, appear to be a slightly higher rate of post-procedure pancreatitis in pregnant women who undergo ERCP.
Intrahepatic cholestasis of pregnancy is characterized by incomplete clearance of bile acids in genetically susceptible women. The main symptom of generalized pruritus usually occurs in the third trimester. Laboratory studies reveal hepatic dysfunction with elevations in serum bile acids. Hepatic transaminase levels may also be modestly elevated, and mild bilirubin elevations may even result in clinical jaundice. Ursodeoxycholic acid (8–10 mg/kg/d) is the treatment of choice and results in decreased pruritus in most women. Cholestyramine has also been used, but it does not appear to be as effective and impairs absorption of fat-soluble vitamins. Vitamin K supplementation is therefore required to help prevent hemorrhagic disease in the fetus. Symptoms ultimately resolve after delivery but often recur in subsequent pregnancies. Adverse fetal outcomes, particularly fetal distress, meconium-stained amniotic fluid, and stillbirth, have been reported in women with cholestasis of pregnancy. Because of these risks, many clinicians recommend antenatal testing in the third trimester and delivery around 38 weeks gestation. Evidence-based recommendations, however, are not available.
Bacq Y et al. Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis. Gastroenterology. 2012 Dec;143(6):1492–501. [PMID: 22892336]
Chan CH et al. ERCP in the management of choledocholithiasis in pregnancy. Curr Gastroenterol Rep. 2012 Dec;14(6):504–10. [PMID: 23011675]
Oto A et al. The role of MR cholangiopancreatography in the evaluation of pregnant patients with acute pancreatobiliary disease. Br J Radiol. 2009 Apr;82(976):279–85. [PMID: 19029218]
Appendicitis occurs in about 1 of 1500 pregnancies. The diagnosis is often difficult to make clinically since the appendix is displaced cephalad from McBurney point. Furthermore, nausea, vomiting, and mild leukocytosis occur in normal pregnancy, so with or without these findings, any complaint of right-sided pain should raise suspicion. CT scanning can help confirm the diagnosis when clinical findings are equivocal, and proper shielding can minimize radiation exposure to the fetus. MRI is also being increasingly used to evaluate for appendicitis in pregnant women and appears to be a reasonable alternative to CT scanning. Unfortunately, the diagnosis of appendicitis is not made until the appendix has ruptured in at least 20% of obstetric patients. Peritonitis in these cases can lead to preterm labor or abortion. With early diagnosis and appendectomy, the prognosis is good for mother and baby.
Blumenfeld YJ et al. MR imaging in cases of antenatal suspected appendicitis—a meta-analysis. J Matern Fetal Neonatal Med. 2011 Mar;24(3):485–8. [PMID: 20695758]
Wilasrusmee C et al. Systematic review and meta-analysis of safety of laparoscopic versus open appendicectomy for suspected appendicitis in pregnancy. Br J Surg. 2012 Nov;99(11):1470–8. [PMID: 23001791]