Section 1. Pregnancy

A 32-year-old G3P2 woman presents with persistent itching in her 31st week of pregnancy. The itching is constant and worse at night. Her pregnancy had been uncomplicated and she has no past history of medical problems. Many excoriations are noted and there are no blisters (Figure 74-1). She has no jaundice or scleral icterus. Her transaminases were greater than 300 and her total bilirubin was elevated at 2.1. Her bile salts were elevated and her hepatitis panel was negative. The ultrasound showed gallstones but no obstruction was seen. A diagnosis of “intrahepatic cholestasis of pregnancy” was made and the patient was treated with oral ursodiol (a bile salt binding agent) and topical 1% hydrocortisone cream. The bile salts and transaminases were decreased and the patient's pruritus improved but did not resolve until after delivery.1

Maternal skin and skin structures undergo numerous changes during pregnancy. There are two general categories of pregnancy-associated skin conditions: (a) benign skin conditions associated with normal hormonal changes of pregnancy (striae gravidarum, hyperpigmentation, hair and vascular changes), and (b) pregnancy-specific dermatoses (prurigo of pregnancy, intrahepatic cholestasis of pregnancy).

• Striae gravidarum—Stretch marks.
• Prurigo of pregnancy—Atopic eruption of pregnancy.
• Spider telangiectasias—Spider nevi or spider angiomas.
• Intrahepatic cholestasis of pregnancy—Pruritus gravidarum.

• Almost all pregnant women develop some increase in skin pigmentation. This usually occurs in discrete areas, probably because of differences in melanocyte density.
• Striae gravidarum (stretch marks) occur in up to 90% of pregnant women by the third trimester.2
• Spider telangiectasias occur in approximately 66% of light-complected and 10% of dark-complected pregnant women, primarily appearing on the face, neck, and arms. The condition is most common during the first and second trimesters.3 Palmar erythema occurs in approximately two-thirds of light-complected and up to one-third of dark-complected pregnant women.2
• Hemorrhoidal, saphenous, and vulvar varicosities occur in approximately 40% of pregnant women.3
• Prurigo of pregnancy (now called atopic eruption of pregnancy) occurs with an incidence of approximately 1 in 300 to 1 in 450 pregnancies.4,5
• Intrahepatic cholestasis of pregnancy occurs in approximately 1 of 146 to 1293 pregnancies in the United States.3

• The most common skin pigmentary change is darkening of the linea alba (Figure 74-2), which is then called the linea nigra.6 It may span from the pubic symphysis to the umbilicus or all the way to the xiphoid process.
• The skin around the areola may also darken and develop a reticular type pattern. Other anatomic areas that develop hyperpigmentation are the nipples, axillae, vulva, perineum, anus, inner thighs, and neck.7 Darkening may also occur in nevi during pregnancy.
• As pregnancy progresses, increased eccrine activity may result in hyperhidrosis (increased sweating) and/or miliaria (“prickly heat”).8 Apocrine activity decreases during pregnancy but increases postpartum, so hidradenitis suppurativa improves during pregnancy but may rebound later.8
• Hypertrophy of sebaceous glands produces small, brown papules on the areolae (Montgomery tubercles, Figure 74-3) in up to half of pregnant women. They usually regress postpartum.8
• Stretch marks (striae distensae, striae gravidarum) begin as pink/violaceous linear patches in the sixth to seventh month of gestation and are a common cosmetic concern among pregnant women (Figure 74-4). They evolve into hypopigmented linear depressions. They are most common on the abdomen, breasts, and thighs, but may also arise on the lower back, buttocks, and upper arms.8 The cause of striae is multifactorial and includes physical factors (e.g., actual stretching of the skin) and hormonal factors adrenocortical (e.g., steroids, estrogen, and relaxin). Although striae fade postpartum, they do not completely disappear.
• Spider angiomas, arterial spiders, or spider nevi may develop, especially in whites. They occur mostly on the neck, face, upper chest, arms, and hands.6 Almost all regress postpartum.
• Palmar erythema may develop and may be limited to the thenar or hypothenar eminence, or may be diffuse and mottled.8
• Acrochordons (skin tags) may develop, enlarge, or increase on the face, neck, axillae, chest, groin, and inframammary area during the second half of pregnancy. Some may regress postpartum.9
• Keloids, leiomyomas, dermatofibromas, and neurofibromas may enlarge during pregnancy.9
• Scalp hair appears thicker during pregnancy as a result of slowing of the normal progression of hairs to the telogen (“resting”) stage, thereby creating a relative increase in anagen hair. Hair loss (telogen effluvium) is common 1 to 5 months postpartum as the percentage of telogen hairs in the scalp normalizes or increases (Figure 74-5).9  Telogen effluvium resolves within 15 months postpartum, but the scalp hair may never return to prepregnancy thickness.9
• Hirsutism may occur on the face, arms, legs, back, and suprapubic region.9 Hirsutism appears to be a result of increased levels of ovarian and placental androgens. Frontoparietal hair loss (androgenic alopecia) may develop late in pregnancy but usually resolves postpartum.
• Saphenous, vulvar, and hemorrhoidal varicosities may increase in number and/or size (see Chapter 66, Hemorrhoids). This may be because of increased blood volume, increased venous pressure, or genetic predisposition. Jacquemier sign refers to venous distention in the vestibule and vagina and is associated with vulvar varicosities, which are particularly difficult to treat.8 Varicosities regress, at least partially, postpartum.
• Vascular type tumors may develop or enlarge during pregnancy. Pyogenic granulomas (Figure 74-6) (granuloma gravidarum, pregnancy tumor, pregnancy epulis) are reddish purple papules that are made up of granulation tissue (see Chapter 161, Pyogenic Granuloma). They usually begin in the first half of pregnancy and then partially regress postpartum. They most commonly appear on the gingiva, but are also common on fingers. Hemangiomas, subcutaneous hemangioendotheliomas, and glomangiomas (glomus tumors) may also occur.
• Atopic eruption of pregnancy is most common in the second or third trimester, but has been reported in all trimesters. It presents with erythematous, excoriated papules on the extensor surfaces of the limbs and trunk.4,5 Lesions are grouped and may appear eczematous. The eruption usually resolves in the immediate postpartum period, although it can persist for months. This should not be confused with intrahepatic cholestasis of pregnancy, which is most common in the third trimester and has no primary skin lesions (Figure 74-4).
• Intrahepatic cholestasis of pregnancy is usually diagnosed based on clinical history and presentation. Patients demonstrate pruritus (with or without jaundice) and no primary skin lesions. Laboratory findings consistent with cholestasis (elevated serum bile acid levels and alkaline phosphatase levels) confirms the diagnosis. Elevated bilirubin levels may or may not be found.2 The etiology remains controversial. It usually resolves postpartum without specific treatment (Figure 74-1).

Striae gravidarum are more common in women who are younger, nonwhite, have larger babies, and have higher body mass indices.2 There is a familial predisposition to striae gravidarum, and women with preexisting breast or thigh striae are also more prone to this condition.10

Intrahepatic cholestasis of pregnancy is associated with a family history of the condition is common, human leukocyte antigen-A31 and -B8.3 It often recurs in subsequent pregnancies and patients have a higher risk of gallstones or a family history of gallstones. It is associated with a higher risk of premature delivery, meconium-stained amniotic fluid, and intrauterine demise.

Nonpharmacologic

• Changes such as hypertrophy of sebaceous glands, spider angiomas, palmar erythema, and varicosities usually regress postpartum and often require only symptomatic or no therapy. SOR C
• Varicosities may be treated with leg elevation, compression with support hose, sleeping on the left side to ease uterine pressure on the great veins, exercise, and avoidance of long periods of standing or sitting. SOR C (see Chapter 52, Venous Stasis). 2

Medications

• The primary treatment for pruritus in pregnancy is symptomatic. SOR C Topical low-potency to mid-potency corticosteroids are safe and can give symptomatic relief of itching.
• Oral antihistamines such as diphenhydramine may be used to relieve itching.2 SOR C See Chapters 75, Pruritic Urticarial Papules and Plaques of Pregnancy and 76, Pemphigoid Gestationis for specific treatment of various pruritic diseases in pregnancy.
• Treatment of stretch marks after pregnancy with 0.1% tretinoin was reported to be beneficial but should not be used during pregnancy because of the risk of birth defects with any retinoid.11 SOR B
• The pruritus of intrahepatic cholestasis of pregnancy may be treated with oral antihistamines. More severe cases require ursodeoxycholic acid (ursodiol [Actigall]) to relieve pruritus and improve cholestasis while reducing adverse fetal outcomes. 2

Surgical

• Persistent, bothersome pyogenic granulomas can be excised and should be sent to pathology to rule out amelanotic melanoma (see Chapter 161, Pyogenic Granuloma). SOR C
• Physical lesions such as skin tags, fibromas, and angiomas may be treated by local surgical or destructive therapies. SOR C
• Laser treatment (585-nm and pulsed-dye laser) may be used to treat striae after pregnancy.2

Complementary and Alternative Therapy

• Many creams, emollients, and oils containing vitamin E, cocoa butter, aloe vera lotion, and olive oil are used to attempt to prevent striae. However, there is no evidence that these treatments are effective. Limited evidence suggests that Centella asiatica extract plus α-tocopherol and collagen-elastin hydrolysates and tocopherol, essential fatty acids, panthenol, hyaluronic acid, elastin, and menthol may be helpful.12 The safety of using Centella asiatica and other components during pregnancy are unclear.13

Conditions should be monitored during pregnancy and the patient regularly reassured. Postpartum, the patient may be followed or treated as needed.

The primary aim of treatment for most skin conditions in pregnancy is to relieve symptoms, as many conditions improve or resolve postpartum. Those conditions that do not resolve can usually be safely treated postpartum when there is no risk to the pregnancy.

Patient Resources

• ACOG Education Pamphlet. Skin Conditions During Pregnancy—www.acog.org/publications/patient_education/bp169.
• Netdoctor—http://www.netdoctor.co.uk/womenshealth/facts/skinrash_pregnancy.htm.
• MedicineNet.com. Skin Problems of Pregnancy—http://www.medicinenet.com/script/main/art.asp?articlekey=52164.

Provider Resources

• Dermnet NZ. Pregnancy Skin Problems —http://www.dermnetnz.org/.
• Common skin conditions during pregnancy. Am Fam Physician. 2007;75(2):211-218. http://www.aafp.org/afp/2007/0115/p211.html.

A 26-year-old pregnant woman presents at 36 weeks of gestation with a progressive itchy rash. The rash started within the abdominal striae (Figure 75-1) and spread to her proximal extremities. This is her first pregnancy and she has never had any rashes like this before. The itching “is maddening.” The patient is diagnosed with pruritic urticarial papules and plaques of pregnancy (PUPPP) and treated with topical steroids and oral antihistamines.

PUPPP is a dermatosis of pregnancy characterized by a papulovesicular or urticarial eruption on the abdomen, trunk, and limbs. Other than maternal itching, PUPPP poses no increased risk of fetal or maternal morbidity.1

• Polymorphic eruption of pregnancy (in the United Kingdom).
• Toxic erythema of pregnancy.
• Linear immunoglobulin (Ig) M dermatosis of pregnancy.
• Bourne toxemic rash of pregnancy.
• Nurse's late-onset prurigo.

• The incidence of PUPPP is 1 out of 160 to 1 out of 300 pregnancies, making it the most common defined dermatosis of pregnancy.2
• Nulliparous patients account for more than 75% of patients with classic PUPPP.3
• PUPPP is also more common with multiple gestations, possibly because of increased abdominal distention or higher hormone levels.4

The rate of recurrence with subsequent pregnancies is unknown.

• The etiology of PUPPP is unknown. PUPPP is more common with excessive stretching of the skin, possibly because of damage to connective tissue, which could result in exposure of antigens that trigger an inflammatory response.2,5 The disease may also represent an immunologic reaction to circulating fetal antigens.
• Onset of PUPPP is usually late in the third trimester, but may develop postpartum.1,3 There are case reports of first and second trimester disease.3 Pruritus may worsen after delivery, but generally resolves by 15 days postpartum. The PUPPP may resolve prior to delivery.

• The disorder is more common with first pregnancies.6
• Multiple gestations.6
• Familial occurrences have been reported.4

Clinical Features

PUPPP is usually diagnosed by its characteristic findings on history and physical examination. PUPPP typically presents with erythematous papules and plaques within striae with periumbilical sparing (Figures 75-1 and 75-2). Extreme pruritus is a hallmark of the disease and is present in all patients.1

Typical Distribution

Abdominal striae are the most common initial site.3 The lesions usually spread to the extremities and coalesce to form urticarial plaques (Figures 75-3 and 75-4). The face, palms, soles, and periumbilical region are usually spared. White halos often surround the erythematous papules and are target-like, exhibiting three distinct rings or color.3

Laboratory Testing

There are no related laboratory abnormalities.

Biopsy

Biopsy is not necessary when the clinical picture is classic. When the diagnosis is uncertain, perform a punch biopsy and consider immunofluorescent studies. IgM or IgA deposits may be found at the dermoepidermal junction or around blood vessels. It is preferable to biopsy a lesion off the abdomen to avoid wound-healing problems on a distended abdomen.

• Pemphigoid gestationis can be differentiated from PUPPP by its bullous lesions (see Chapter 76, Pemphigoid Gestationis).
• Erythema multiforme produces target lesions that may affect the palms and soles (see Chapter 177, Erythema Multiforme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis).
• Drug reactions produce various types of erythematous eruptions on the trunk and extremities. History of a new drug exposure helps to distinguish this from PUPPP (see Chapter 203, Cutaneous Drug Reactions).
• Scabies infestations produce severe itching from the mite burrows that are common between the fingers and in areas of skin folds (see Chapter 143, Scabies).
• Viral exanthems may produce all types of erythematous eruptions that can be pruritic at times. The history of a fever along with upper respiratory symptoms should help to differentiate these eruptions from PUPPP (see Chapters 126, Measles and 127, Fifth Disease).

Nonpharmacologic

• Symptom control is the main goal. Aggressive therapy is not recommended since the condition is self-limiting. SOR C
• Early delivery to relieve symptoms is rarely required.

General symptom relief measures such as cool baths, frequent application of emollients, wet soaks or cool packs applied to the skin provide some symptomatic relief. 7 SOR C

Medications

• First-line therapy consists of topical steroids and oral antihistamines to alleviate symptoms. Systemic corticosteroids are occasionally required in cases of extreme pruritus. SOR C
• Start with a mid-potency topical corticosteroid such as 0.1% triamcinolone bid to tid. Pregnancy class B. SOR C High-potency, topical, corticosteroids such as fluocinonide may be applied sparingly bid to tid as severity warrants. Pregnancy class B. SOR C
• Diphenhydramine 25 to 50 mg PO bid to qid or similar antihistamines may be used for symptomatic relief of pruritus. Pregnancy class B. SOR C

In severe cases, oral prednisolone, 40 to 60 mg daily, may induce a rapid resolution of symptoms.7 SOR C

Apart from itching and related discomfort, the prognosis for the mother is unaffected. Recurrence of the condition in subsequent pregnancies is rare and tends to be less severe than the first episode.7

Pruritus may worsen immediately after delivery, but generally resolves by 2 weeks postpartum.

Routine prenatal and postpartum care should be continued.

• When discussing treatment options, inform the patient that the condition is self-limited, so therapy is based on making the patient comfortable while minimizing the potential risks involved in the use of medications.6
• Symptom control with topical steroids and antihistamines is the main goal.

Patient Resources

• About.com. PUPPP—http://dermatology.about.com/cs/pregnancy/a/puppp.htm.
• DermNet NZ. PUPPP—http://dermnetnz.org/reactions/puppp.html.

Provider Resources

• EMedicine. Pruritic Urticarial Papules and Plaques of Pregnancy—http://www.emedicine.com/derm/topic351.htm.
• Medscape Today. Specific Pregnancy Dermatoses: Pruritic Urticarial Papules and Plaques of Pregnancy—http://www.medscape.com/viewarticle/707663_3.
• Tunzi M, Gray GR. Common skin conditions during pregnancy. Am Fam Physician. 2007;75:211-218. http://www.aafp.org/afp/2007/0115/p211.html.

A 37-year-old pregnant woman presented to the hospital with severe preeclampsia. After all medical methods were tried and failed to control her severe preeclampsia, a joint decision was made to induce labor to save the life of the mother. The pregnancy was too early for the fetus to survive. The following day she began to develop the lesions seen in Figures 76-1, 76-2, 76-3, and 76-4. A diagnosis of pemphigoid gestationis was made. Her past history includes antiphospholipid syndrome with multiple pregnancy losses but two live children. This was her third episode of pemphigoid gestationis. A photograph of her previous episode is included to see how similar the periumbilical bulla was to her current episode of pemphigoid gestationis. A new biopsy was not performed given that her previous biopsy was on file and the clinical picture was consistent with a recurrence of this disease. She was treated with oral prednisone and began to improve rapidly (Figure 76-5).

Pemphigoid gestationis is a rare autoimmune bullous dermatosis of pregnancy. The disease was originally known as herpes gestationis because of it visual similarities to herpes simplex infection. However, that term has fallen out of favor because pemphigoid gestationis is not associated with active or prior herpes virus infection.

Herpes gestationis.

• Pemphigoid gestationis is a rare disease that occurs in 1 in 1700 to 1 in 50,000 pregnancies.1,2
• Pemphigoid gestationis has an estimated prevalence of 1 case in 50,000 to 60,000 pregnancies in the United States.
• It has been linked to the presence of human leukocyte antigen (HLA)-DR3, HLA-DR4, or both.3
• It is rarely associated with molar pregnancies and choriocarcinoma.3

• Pemphigoid gestationis, which has classically been called herpes gestationis, is defined as a bullous or blistering disease that is associated with pregnancy or with trophoblastic tumors.
• As there is no connection with a herpes virus, the preferred name is now pemphigoid gestationis. It is associated with an increased risk of fetal morbidity and mortality.
• The pathophysiology of the disease involves immunoglobulin (Ig) G antibodies that attack cells in the skin.
• The IgG attacks the same antigen (bullous pemphigoid antigen) as in bullous pemphigoid.2 This antigen is a transmembrane protein that is part of the hemidesmosome, which connects the basal cells of the epidermis to the basement membrane.
• When the inflammatory response is activated, the hemidesmosomes are destroyed and the epidermis separates from the dermis.2
• It is unknown why some patients form these antibodies.
• Rarely, pemphigoid gestationis persists for years postpartum.1,2
• There is no scarring from the lesions.

Pemphigoid gestationis in a prior pregnancy.

Clinical Features: History and Physical

• Pemphigoid gestationis typically erupts during the second or third trimester and, rarely, postpartum and first trimester. Symptoms may abate at the end of pregnancy; however, flares can occur immediately after delivery.
• Pruritus sometimes precedes the rash and vesicles may develop early.
• The initial manifestations are erythematous urticarial patches and plaques, which typically start around the umbilicus. The lesions progress to tense vesicles. (Figures 76-1, 76-2, 76-3, 76-4, and 76-5).

Typical Distribution

The rash begins on the trunk around the umbilicus as pruritic papules or plaque and may progress to bullae (Figures 76-4 to 76-5).1,2 Lesions may occasionally be seen on the palms and soles, and rarely on the face or mucous membranes.

Laboratory Testing

There are no diagnostic laboratory tests.

Biopsy

Skin biopsy including the edge of a blistering lesion reveals a subepidermal vesicle with a perivascular lymphocytic and eosinophilic infiltrate.

• Eosinophils may appear at the dermoepidermal junction and inside the vesicle; the degree of eosinophilia correlates with disease severity.
• Basal cell necrosis and papillae edema are usually present.

A skin biopsy of perilesional skin for indirect immunofluorescent staining shows complement 3 in a homogeneous linear band at the basement membrane. This is pathognomonic for pemphigoid gestationis.

• Papular urticarial papules and plaques of pregnancy (PUPPP) may mimic pemphigoid gestationis, especially early in the disease. However, PUPPP usually begin in the striae, whereas pemphigoid gestationis is usually periumbilical. Most importantly, PUPPP does not develop large bullae as does pemphigoid gestations (see Chapter 75, Pruritic Urticarial Papules and Plaques of Pregnancy).
• Dermatitis herpetiformis is a very pruritic, vesicular skin eruption. It is a chronic recurrent symmetric vesicular eruption that is usually associated with gluten-induced enteropathy. Men are more often affected than women (see Chapter 186, Other Bullous Disease).
• Erythema multiforme secondary to pregnancy, infection, or drug exposure can mimic pemphigoid gestationis. Biopsy with routine histology can usually distinguish between these disorders (see Chapter 177, Erythema Multiforme, Stevens-Johnson Syndrome, and Toxic Epidermal).
• Contact dermatitis and drug reactions may have a similar appearance and history of exposure to a contact allergen or medication can help to distinguish between these reactions and pemphigoid gestationis (see Chapters 146, Contact Dermatitis and 203, Cutaneous Drug Reactions).
• Bullous pemphigoid produces similar lesions, but rarely starts in pregnancy or starts around the umbilicus (see Chapter 184, Bullous Pemphigoid).
• Urticaria may appear similar to early pemphigoid gestationis (see Chapter 150, Urticaria and Angioedema).

Nonpharmacologic

Tepid baths, compresses, and emollients may help alleviate pruritus.

Medications

• Topical steroids and oral antihistamines should be administered in early or mild cases, but are usually ineffective in more severe cases. SOR C
• Systemic steroids, such as prednisone (0.5 mg/kg per day), are effective to control most cases.4 SOR C The dose may be tapered and eventually discontinued in many pregnancies.

Pemphigoid gestationis typically regresses spontaneously without scarring within weeks to months after delivery. It may recur in subsequent pregnancies or may be precipitated by the use of oral contraceptives.

• Follow-up of the mother and child are essential because of the following issues:
  • The fetus during a pregnancy in which the mother has pemphigoid gestationis is at risk for growth restriction and prematurity.
  • Mild placental insufficiency may result from an immune response between placental antigens and the disease-related antibodies.7
• Cutaneous involvement in infants of affected mothers is rare (5% to 10% have urticarial, vesicular, or bullous lesions) and abates with clearance of the maternal antibodies.6
• The mother is at high risk of recurrent pemphigoid gestationis with subsequent pregnancies and at an increased lifetime risk of Graves disease.2,5

• Pemphigoid gestationis may abate prior to delivery, but 75% of patients flare postpartum requiring reinstatement of treatment.
• At least 25% of patients will flare with oral contraceptive pill use.
• Most cases spontaneously resolve in the weeks to months following delivery.
• The disease usually recurs with future pregnancies and often worsens with repeated episodes, but may also skip some pregnancies.2,5

Patient Resources

• About.com. Pemphigoid Gestationis—http://dermatology.about.com/cs/pregnancy/a/pemphgest.htm.
• DermNet NZ—http://www.dermnetnz.org/immune/pemphigoid-gestationis.html.
• Patient.co.uk. Pemphigoid Gestationis—http://www.patient.co.uk/doctor/Pemphigoid-Gestationis-(PG).htm.
• European Academy of Dermatology and Venereology. Pemphigoid (Herpes) Gestationis (PG)—http://www.eadv.org/patient-corner/leaflets/eadv-leaflets/pemphigoid-herpes-gestationis-pg/.

Provider Resources

• EMedicine. Pemphigoid Gestationis—http://emedicine.medscape.com/article/1063499-overview.
• ARUP. Pemphigoid Gestationis: Herpes Gestationis—http://www.arupconsult.com/Topics/PemphigoidGestationis.html.
• Tunzi M, Gray GR. Common skin conditions during pregnancy. Am Fam Physician. 2007;75:211-218—http://www.aafp.org/afp/2007/0115/p211.pdf.

A 22-year-old woman presents with no menstrual period for approximately 2 months (she has irregular menses.) She is complaining of morning sickness but is otherwise feeling well. A urine pregnancy test confirms she is pregnant. Figure 77-1 shows a fetus of 9 weeks estimated gestational age (EGA).

Obstetrical ultrasound has become a vital tool in our ability to properly care for the pregnant patient. Vast technologic improvements have made visualization of the pregnancy even better and improved our diagnostic capabilities, ranging from the normal pregnancy to the extremely early ectopic pregnancy. Ultrasonography (US) allows for a relatively detailed assessment of fetal gestational age, development, number of fetuses, and anatomy in utero. Most pregnancies in the United States undergo ultrasound imaging for various indications.

• Women who receive antenatal care have lower maternal and perinatal mortality and better pregnancy outcomes.1 However, the optimal components of prenatal care have not been rigorously examined in well-designed studies.
• In the United States in 2003, 84.1% of pregnant women obtained prenatal care in the first trimester, and only 3.5% received no care or initiated prenatal care in the third trimester.

• Ultrasound is used to estimate gestational age and to calculate the expected date of delivery (EDD). Ultrasound is especially helpful when menses are irregular, the last menstrual period (LMP) is unknown, or in patients who conceived while using hormonal contraceptives. A Cochrane review noted with more accurate dating there was a reduction in intervention for postterm pregnancy.2
• The Routine Antenatal Diagnostic Imaging with Ultrasound (RADIUS) trial was a randomized trial of routine obstetrical ultrasound screening.3 It included more than 15,000 women in the United States. The trial showed that routine ultrasound screening was associated with a significantly increased detection of fetal anomalies, but no improvement in any perinatal outcome, including mortality, preterm birth, birth weight, and neonatal morbidity.
• First trimester vaginal bleeding is found in 20% to 40% of pregnancies. The differential diagnoses include possible spontaneous abortion, ectopic pregnancy, and gestational trophoblastic disease.
• Ectopic pregnancy causes a significant degree of morbidity and mortality if untreated, often through tubal rupture with potentially life-threatening hemorrhage. Identification of an intrauterine pregnancy effectively excludes the possibility of an ectopic in almost all cases, unless conception involved assisted reproductive technology.
• Threatened, inevitable, incomplete, or complete spontaneous abortion may cause first trimester bleeding. Up to one-third of recognized pregnancies end in early pregnancy loss. Ectopic pregnancy may also be a concern. US may be used to determine if a gestational sac or yolk sac is present in the uterus.
• First trimester transvaginal ultrasound used in conjunction with serum screening is the most sensitive noninvasive technique to detect aneuploidy. When performed in the first trimester, nuchal translucency as well as serum pregnancy-associated plasma protein A (PAPP-A) and β-human chorionic gonadotropin (β-hCG) levels are evaluated, which effectively detect 82% to 87% of trisomy 21. Integrated screening would also include a quad screen in second trimester, which carries a 94% to 96% detection rate.4

• The goals of a basic first trimester ultrasound examination include3:
  • Confirm the presence of an intrauterine (or evaluate suspected extrauterine) pregnancy.
  • Assess gestational age.
  • Determine fetal viability.
  • Determine the cause of vaginal bleeding.
  • Evaluate pelvic or lower abdominal pain.
  • Determine whether a multiple gestation is present.
  • Evaluate maternal pelvic organs for congenital or acquired abnormalities.
• Fetal crown-rump length is used to calculate gestational age and may be performed via the transvaginal or the transabdominal route. Because the variation in size from fetus to fetus is minimal in the first trimester and minimal flexion, this is the optimal time to obtain an estimate of gestational age. Transvaginal US is typically used early for evaluation of the gestational sac, yolk sac, and developing embryo, while transabdominal US usually provides better visualization later in the first trimester. In obese patients, transvaginal US in early pregnancy can provide better visualization for more accurate dating.
• During the first 5 weeks of pregnancy, the endometrium has a “trilaminar” appearance, and usually does not show distinct evidence of an intrauterine pregnancy. The gestational sac is the first detectable sign on ultrasound. Initial gestational age measurements are based on diameter of the sac. The yolk sac (Figure 77-2) is the first anatomic structure to appear within the gestational sac around the fifth week of gestation. A gestational sac diameter of 8 mm or greater with an empty or no fetal pole yolk sac indicates an abnormal gestation.5
• The embryonic disc becomes visible at about a gestational age of 5 to 6 weeks.6 If the embryo is visible, but too small to measure, detection of cardiac activity establishes a gestational age of approximately 6 weeks. Direct measurement of the crown-rump length of the embryo provides the most accurate estimate of gestational age once the fetal pole is evident (Figure 77-3). The crown-rump length is the mean of three measurements of the longest straight-line length of the embryo from the outer margin of the cephalic pole to the rump.
• The biparietal diameter may be used later in the first trimester (Figure 77-4). It is highly reproducible and can predict gestational age within 7 days when measured between 14 and 20 weeks of gestation. The biparietal diameter should be measured on a plane of section that intersects both the third ventricle and thalami. The falx cerebri should be visible. The cursors are placed on the outer edge of the proximal skull and the inner edge of the distal skull to take the measurement. The femur length can be assessed by 10 weeks gestational age, but is more accurate after 20 weeks' gestation.

Patient Resources

• Obstetric ultrasound by Dr. Joseph Woo—http://www.ob-ultrasound.net/.
• RadiologyInfo—http://www.radiologyinfo.org/en/info.cfm?pg=obstetricus&bhcp=1.

Provider Resources

• Obstetric Ultrasound by Dr. Joseph Woo—http://www.ob-ultrasound.net/.

A 23-year-old pregnant gravida 2, para 1 woman is being seen for ultrasound because of her uncertain dates. Her best recollection of her last period gave her an estimated gestational age (EGA) of 19 weeks. Her vital signs are normal and her fundal height is 20 cm. Figures 78-1, 78-2, and 78-3 are still images taken from her ultrasound examination demonstrating an EGA of 21 weeks and 6 days by measurement of the baby's biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). All four measurements allow the computer to calculate an estimated fetal weight of 431 g. The pregnancy proceeded without complications and the patient delivered a healthy boy at 403/7 weeks based on the ultrasound calculated estimated date of delivery. No interventions were needed for postdates because of the ultrasound calculations earlier in the pregnancy.

The ideal time to perform an obstetric ultrasound is between 18 and 20 weeks' gestation. The fetus has developed all of its organ systems and is large enough to visualize these in detail. If resources are limited or patient costs are an issue, the second trimester ultrasound provides the most bang for the buck.

• Second and third trimester ultrasound examination can be used to determine fetal number and presentation, and for documentation of fetal cardiac activity, placental location, and amniotic fluid volume.
• Second trimester is a good time to perform ultrasound for fetal assessment for gestational age and weight, and it is also an integral part of performing diagnostic amniocentesis.
• If only a single ultrasound can be performed on a patient, optimal timing is 18 to 20 weeks. Fetal anatomy is best seen during this interval. If fetal abnormalities are detected, a more detailed examination (level 2 ultrasound) by a specialized sonographer is indicated.
• Ultrasound examination is indicated to establish the number of fetuses when a multiple gestation pregnancy is suspected. Risk factors for a multiple gestation pregnancy include assisted reproductive technology, family history of twins (or higher multiples), and uterine size larger than that expected by menstrual dating. The number of fetuses can be best established by obtaining an image that includes a cross-section of all fetal poles that have distinct cardiac activity within a single frame.
• The cervix and lower uterine segment may be imaged in the second trimester to look for funneling (membranes protruding into the cervical canal), a short cervix that is a significant risk factor for preterm labor.

The placental location, appearance and relationship to the internal cervical os should be recorded.1

• Fetal abnormalities that may be reliably diagnosed by ultrasound include achondroplasia, anencephaly, cleft lip, clubfoot, duodenal atresia, fetal hydrops, gastroschisis, hydrocephalus, omphalocele, transposition of the great vessels, cardiac, pulmonary and renal abnormalities, and spina bifida. If anomalies are suspected, a level 2 ultrasound with a perinatologist is indicated.
• Up to 5% of pregnancies will have placentas that partially or completely cover the internal cervical os at 16 to 18 weeks of gestation. Only 1 in 10 of these will continue to cover the internal os in the late third trimester.2 Placentas that are clear of the cervix in early pregnancy will not encroach upon it later.

• Evaluating the possibility of a fetal anomaly is best done by ultrasound examination after 16 weeks of gestation as earlier examination may be limited by fetal size and development.
• The sensitivity and specificity of the procedure for detecting congenital abnormalities varies depending upon the specific defect, the gestational age, the quality of the ultrasound unit, and the skill of the ultrasonographer.
• Ultrasound examination is the main diagnostic modality used to evaluate second and third trimester bleeding. The major placental causes of vaginal bleeding at this time are placenta previa and abruptio placentae. A transvaginal obstetric ultrasound examination can identify placental location, and is safe even when placenta previa is present. Preterm labor is another cause of vaginal bleeding and the cervical length can be measured transvaginally to assess this risk. The normal cervical length can be seen in Figure 78-1. The images should be obtained after the mother has emptied her bladder to avoid displacement of the anterior lower uterine segment thus producing a false-positive test.3
• Fetal intrauterine growth limiting disorders are more likely when the uterine size is less than appropriate for gestational age, a prior pregnancy has been affected by growth restriction, with maternal hypertension, and in multiple gestations. Ultrasound cannot distinguish between a constitutionally small fetus and a pathologically small fetus. Decreased amniotic fluid volume and below normal interval growth make placental insufficiency more likely.

Performing the Procedure

• The four standard biometric parameters commonly used to estimate gestational age and/or fetal weight in the second trimester are: BPD, HC (Figure 78-2), AC (Figure 78-3), and FL (Figure 78-4).4 They are usually obtained by transabdominal ultrasound examination, and the fetal weight is calculated.
• The BPD (Figure 78-2) is a highly reproducible measurement and can predict gestational age within ±7 days when the ultrasound is performed between 14 and 20 weeks' gestation, although the best time to get an accurate date is in the first trimester. The BPD should be measured on a plane that includes both the third ventricle and the thalamus. The cursors are placed on the outer edge of the proximal skull and the inner edge of the distal skull and the BPD measured.
• The cephalic index is ratio of the BPD and the occipitofrontal diameter multiplied by 100. It should be used where the BPD may be inaccurate, such as with breech presentations, oligohydramnios, premature rupture of the membranes, and neural tube abnormalities.
• The measurement of fetal HC also accurately estimates gestational age, and is especially useful in the setting of growth disorders (Figure 78-2). The accuracy decreases in the second half of pregnancy. The HC should be measured on a plane that includes the third ventricle, the thalamus, the cavum septum pellucidum anteriorly, and the tentorial hiatus posteriorly. Unlike the BPD measurements, the HC measurement is obtained by placing the cursors on the outer margins of the calvarium bilaterally.
• The AC (Figure 78-3) is the least accurate in predicting gestational age, being accurate within 2 weeks in the second trimester. It is most often used for estimations of fetal weight and interval growth evaluations rather than fetal dating. The measurement should be taken at the level of the largest diameter of the fetal liver where the right and left portal veins join. The four calipers are placed around the abdomen on the skin edge to draw a circular line for AC measurement.
• FL (Figure 78-4) can be measured and is accurate to within 1 week before 20 weeks' gestation. Align the transducer along the long axis of the femoral bone and visualize either the femoral head or the greater trochanter proximally, and the end of the femur or the femoral condyle distally. Make sure you are measuring the femur and not another long bone in the arm or leg. Place the calipers at the bone and cartilage junction and measure only ossified bone, not including the femoral head.
• Many providers will often show expectant parents images of the baby's face (Figures 78-5 and 78-6), hands (Figure 78-7), and sex (Figures 78-8 and 78-9).
• The placenta and its relationship to the cervix should be examined for signs of placenta previa.

Cervical length or funneling of the cervix should be measured if there is a history of or current evidence of preterm labor or history of incompetent cervix. Cervical length is determined as the distance ­between the internal and external os. In patients at risk for cervical shortening or incompetence the operator can apply fundal pressure or scan the patient in the standing position to help identify these women3 (Figure 78-10).

Patient Resources

• Obstetric ultrasound by Dr. Joseph Woo—http://www.ob-ultrasound.net/.
• RadiologyInfo—http://www.radiologyinfo.org/en/info.cfm?pg=obstetricus&bhcp=1.

Provider Resources

• The Society of Obstetricians and Gynaecologists of Canada (SOGC) recommends a single “routine” ultrasound evaluation at 16 to 20 weeks in all pregnancies and suggests that 8 markers be evaluated based on an EBM review of the literature—http://www.sogc.org/guidelines/pdf/JOGC-june05-Fetalmarkers-revised-ENG-CPG.pdf.
• Perinatology.com. Level 2 Ultrasound—http://www.perinatology.com/ultrasound.htm.
• Obstetric ultrasound by Dr. Joseph Woo—http://www.ob-ultrasound.net/.

A 26-year-old woman gravida 3, para 2-0-0-2 with a singleton pregnancy at 27 weeks' gestation is concerned because her sister had a fetal demise and she thinks her baby is moving less. An ultrasound demonstrating normal anatomy (Figures 79-1, 79-2, and 79-3) and strong fetal heart motion is very reassuring (Figure 79-4).

Ultrasound usage in the third trimester of pregnancy is most often utilized to determine fetal number, presentation, and growth issues. This later pregnancy scan is also used to document fetal cardiac activity, placental location, and amniotic fluid volume, as well as provide a method for antenatal fetal assessment.

• A Cochrane review of 7 studies showed no difference in obstetric, antenatal, or neonatal interventions between women undergoing routine late ultrasound examination after 24 weeks and those who did not.1 In addition, there was no difference in perinatal outcome measures, such as admission to a neonatal intensive care unit, birthweight less than 10th percentile, or perinatal mortality.
• Hydrops fetalis is the accumulation of fluid in fetal tissues and body cavities, usually a result of immune pathologic conditions (Figure 79-5). Serial ultrasound examinations are useful for following pregnancies at risk for developing hydrops or to evaluate treatment. As well as utilizing middle cerebral artery peak-systolic velocity as a noninvasive tool to predict fetal anemia.2
• Ultrasound may also be used to evaluate third trimester bleeding. The major placental causes of vaginal bleeding at this time are placenta previa (Figure 79-6) and abruptio placentae.
• Ultrasound can safely image maternal abdominal organs during pregnancy. Ovarian cysts, uterine leiomyoma, renal obstruction, and gallbladder or liver disease can be evaluated without using ionizing radiation.

In pregnancies complicated by fetal growth restriction and maternal hypertensive disorders, umbilical artery Doppler sonography can be used for fetal surveillance and monitoring well-being. The values measured are peak-systolic frequency shift (S) and end-diastolic frequency shift (D). This S-to-D ratio gives information about downstream impedance to flow. For example uteroplacental insufficiency will show rising impedance to fetal placental vascular bed, which shows a decline in end-diastolic velocity and an overall increase in these Doppler indices.3

If there is an increased risk for in utero fetal demise or significant risk factors for fetal anemia then fetal surveillance can be performed with the biophysical profile (BPP). This is the sonographic assessment of four fetal variables: fetal movement, fetal tone, fetal breathing, and the amniotic fluid volume, plus the results of the nonstress testing.3

• Ultrasound-based determination of estimated date of delivery (EDD) has been shown to improve dating and thus reduce intervention for postterm pregnancy. One randomized controlled trial evaluated the effect of routine ultrasound examinations at 18 and 32 weeks of gestation on the accuracy of dating and pregnancy outcome in a low-risk population.4 They found that ultrasound screening reduced the incidence of induced labor for postterm pregnancy by 70%, and also reduced the incidence of induction for all causes. They also found that the proportion of 5-minute Apgar scores less than 8 and the need for positive pressure ventilation were both lower in the screened group.
• Although ultrasound EDD determination as late as 34 weeks can reduce the number of pregnancies diagnosed as postterm, first trimester ultrasound in a low-risk population is more effective than later ultrasound in decreasing postterm pregnancy.
• Accurate assessment of gestational age is important so as not to inappropriately initiate tocolysis for near-term labor.
• Signs suggestive of fetal maturity may also be found on ultrasound. The femoral epiphyseal ossification center can be visualized by 32 weeks' gestational age, and proximal tibial center can be visualized by 35 weeks' gestational age. The proximal humeral epiphysis also appears in the late third trimester and correlates well with fetal lung maturity.
• Twin pregnancies are at increased risk of complications, such as fetal heart rate abnormalities and complications as a result of malpresentation. When both twins are found on ultrasound to be vertex (42% of twins) a trial of labor with the goal of a vaginal delivery is appropriate. When one twin is nonvertex (38% of twins) options include cesarean delivery of both twins, or attempted vaginal delivery of one or both twins.5,6
• Parents are now paying for 4D ultrasounds (3D images in real time, time being the fourth dimension) so that they can see and get pictures of their developing child. Although the 4D ultrasound is not a standard medical device (Figure 79-7), it is being utilized to better characterize certain anomalies, such as facial clefts, neural tube defects, and skeletal malformations.7

If there is suspicion of unusual fetal growth, restricted or macrosomic, a third trimester growth scan is obtained for evaluation and continued plan of care.

The BPP is a noninvasive, easily performed, accurate means for predicting the presence of significant fetal anemia. Approximately 70% to 90% of late fetal deaths display evidence of fetal compromise prior to demise.3 Ultrasound detection of these fetal signs can allow appropriate intervention to ideally prevent adverse fetal sequelae.

Umbilical artery and middle cerebral artery Doppler measurements should be integrated with other existing modalities of antepartum fetal monitoring to determine their clinical usefulness.3

• Once BPPs are initiated in women requiring fetal surveillance, this test should be repeated on a weekly or twice weekly basis until delivery.

When a patient has placenta previa diagnosed on ultrasound, advise patient to avoid coitus, digital cervical examination, and exercise. Counsel her to seek immediate medical attention if there is any vaginal bleeding or uterine contractions. Advise her that cesarean delivery is the delivery route of choice.8

Patient Resources

• Obstetric ultrasound by Dr. Joseph Woo—http://www.ob-ultrasound.net/.
• March of Dimes pregnancy education center—http://www.marchofdimes.com/pnhec/159_523.asp.

Provider Resources

• OB-GYN ultrasound online—http://www.fetalsono.com/index.html.
• Perinatology.com. Level 2 ultrasound—http://www.perinatology.com/ultrasound.htm.
• Obstetric ultrasound by Dr. Joseph Woo—http://www.ob-ultrasound.net/.