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Obstentrics_Williams. Shaw JG, Asch SM, Kimerling R, et al: Posttraumatic stress disorder and risk of spontaneous preterm birth. Obstet Gynecol 124(6): 1111, 2014 Silverman ME, Reichenberg A, Savitz DA, et al: The risk factors for postpartum depression: a population-based study. Depress Anxiery 34(2): 178, 2017 Siu AL, US Preventive Services Task Force (USPSTF), Bibbins-Domingo K, et al: Screening for depression in adults: US Preventive Services Task Force recommendation statement. JAMA 315(4):380,t2016 Smith MV, Busser 0, Ganann R, et al: Women's care-seeking experiences after referral for postpartum depression. Qual Health Res 18: 1161, 2008 Smith MV, Howell H, Wang H, et al: Success of mental health referral among pregnant and postpartum women with psychiatric distress. Gen Hosp Psychiatry 31(2):155,t2009 Steinberg JR, McCulloch CE, Adler NE: Abortion and mental health: findings from the National Comorbidiry Survey Replication. Obstet Gynecol 123:263,t2014


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Obstentrics_Williams. Steinberg JR, McCulloch CE, Adler NE: Abortion and mental health: findings from the National Comorbidiry Survey Replication. Obstet Gynecol 123:263,t2014 Straub H, Adams M, Kim JJ, et al: Antenatal depressive symptoms increase the likelihood of pre term birth. Am J Obstet GynecoIt207:329.el, 2012 Tam H, Chung T: Psychosomatic disorders in pregnancy. CUlT Opin Obstet Gynecol 19: 126, 2007 Tarney CM, Berry-Caban C, Jain RB, et al: Association of spouse deployment on pregnancy outcomes in a U.S. military population. Obstet Gynecol 126(3):569,t2015 Torgerson L, Von Holle A, Reichborn-Kjennerud T, et al: Nausea and vomiting of pregnancy in women with bulimia nervosa and eating disorders not otherwise specified. Int J Eat Disord 41t:722, 2008 Van den Bergh BR, Mulder EJ, Mennes M, et al: Antenatal maternal anxiery and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review. Neurosci Biobehav Rev 29(2):237, 2005


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Obstentrics_Williams. Van Lieshout RJ, Voruganti LP: Diabetes mellitus during pregnancy and increased risk of schizophrenia in ofspring: a review of the evidence and putative mechanisms. J Psychiatry Neurosci 33(5):395, 2008 Venkatesh KK, Kaimal A, Nadel H, et al: Implementation of universal screening for depression during pregnancy: feasibiliry and impact on obstetric care. 215(4):517.e1,t2016 Viguera AC, Whitfield T, Baldessarini RJ, et al: Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry 164(12): 1817,t2007 Vythilingum B: Anxiery disorders in pregnancy. Curr Psychiatry Rep 10(4): 331,t2008 Weinberg MK, Tronick EZ: The impact of maternal illness on infant development. J Clin Psychiatry 59:53, 1998 Wisner KL, Parry BL, Piontek CM: Postpartum depression. N Engl J Med 347:t194,t2002


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Obstentrics_Williams. Weinberg MK, Tronick EZ: The impact of maternal illness on infant development. J Clin Psychiatry 59:53, 1998 Wisner KL, Parry BL, Piontek CM: Postpartum depression. N Engl J Med 347:t194,t2002 Yaeger 0, Smith HG, Altshuler LL: Arypical antipsychotics in the treatment of schizophrenia during pregnancy and the postpartum. Am J Psychiatry 163:2064,t2006 Yonemoto N, Dowswell T, Nagai 5, et al: Schedules for home visits in early postpartum period. Cochrane Database Syst Rev 8:CD009326, 2017 Yonkers A, Vigod 5, Ross LE: Diagnosis, pathophysiology, and management of mood disorders in pregnant and postpartum women. Obstet Gynecol 117:961,201t1 Yonkers A, Wisner KL, Stewart DE, et al: he management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol 114:703,t2009


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Obstentrics_Williams. Yost NP, Bloom SL, McIntire DD, et al: A prospective observational study of domestic violence during pregnancy. Obstet Gynecol 106(1):61, 2005 Zerbe KJ, Rosenberg J: Eating disorders. Clinical Updates in Women's Health Care. American College of Obstetricians and Gynecologists, Vol VU, No.t1, January 2008 PREGNANCY-SPECIFIC DERMATOSES .i...i.....i....i... 1184 SPECIFIC TO PREGNANCY.. . . . . . . . . . . . . . . . . . . . . .. 1186 DERMATOLOGICAL TREATMENT.. . . . . . . . . . . . . . . .. 1188 Herpes Gestationis-This disease, more requenty known as dermatitis herpetormis is an inlammatory supeicialy seated multorm herpetiorm eruption, which is characterized by erythematous, vesicular, pustular, and bulous lesions. -J. Whitridge Williams (1903)


Obstentrics_Williams

Obstentrics_Williams. -J. Whitridge Williams (1903) Four dermatoses considered unique to pregnancy include intrahepatic cholestasis of pregnancy, pruritic urticarial papules and plaques of pregnancy (PUPPP), atopic eruption of pregnancy (AEP), and pemphigoid gestationis (PG). Descriptions of these are given in Table 62-1. As a group, these are diagnosed in up to 5 percent of pregnancies (Chander, 2011). Their gross appearance may be similar to each other or to other skin disorders, and pruritus is a common feature of all four. Only intrahepatic cholestasis and pemphigoid gestationis have been linked with adverse fetal outcomes. • Intrahepatic Cholestasis of Pregnancy


Obstentrics_Williams

Obstentrics_Williams. • Intrahepatic Cholestasis of Pregnancy Previously termed pruritus gravidarum, this condition is found in 0.5 percent of pregnancies (Wikstrom Shemer, 2013). In contrast to the other pregnancy-speciic dermatoses, intrahepatic cholestasis of pregnancy generally has no primary skin lesions. Rarely, a rash precedes pruritus, which is usually associated with abnormally elevated serum bile acid levels and mildly increased hepatic aminotransferase levels (Chao, 2011). Adverse fetal efects have been linked to this condition, and it is discussed in detail in Chapter 55 (p. 1059). his rare autoimmune bullous disease is notable for its maternal and fetal efects. Initially, pruritic papules and urticarial plaques form and are then followed in most cases after 1 to 2 weeks by vesicles or bullae. Lesions are frequently distributed periumbilically, often develop on other skin surfaces, but spare mucous membranes, scalp, and face (Fig. 62-1).


Obstentrics_Williams

Obstentrics_Williams. Previously termed hepes gestationis, pemphigoid gestationis is not related to the herpesvirus. Instead, maternal immunoglobulin G (IgG) antibodies target collagen VII found in the basement membrane of skin and amnionic epithelium (Kelly, 1988; Shimanovich, 2002). Collagen VII is also termed bullous pemphigoid 180 (BP 180). Autoantibody binding to collagen VII activates complement to promote eosinophil chemotaxis to the antigenantibody complexes. Eosinophilic degranulation damages the dermal-epidermal junction and leads to blistering (Engineer, 2000). In most cases, PG develops during a irst pregnancy. It may rarely be associated with gestational trophoblastic disease (Matsumoto, 2013; Takatsuka, 2012). Most subsequent pregnancies are also afected, usually earlier and more severely (Tani, 2015). Whites have a higher incidence, and other autoimmune diseases are frequent in afected women (Shornick, 1984, 1992).


Obstentrics_Williams

Obstentrics_Williams. PG usually begins during the second or third trimester, but postpartum onset or exacerbation is common (Lawley, 1978). The disease course is often marked by antepartum flares and remissions. And, especially in cases with early-onset and blistering, PG has an association with preterm birth and fetalgrowth restriction (Al-Saif, 2016; Chi, 2009). One theory for TABLE 62-1 . Pregnancy-specific Dermatoses Cholestasis of Common No primary lesions, secondary Increased perinatal Anti pru ritics, pregnancy excoriations from scratching morbidity cholestyramine, plaques of on abdomen, thighs, buttocks, pregnancy (PUPPP) especially within striae, but Atopic eruptions of None Anti pru ritics, Eczema of pregnancy Common Dry, red scaly patches on emollients, topicalextremity flexures, neck, face corticosteroids, oral Prurigo of pregnancy Common 1-5 mm pruritic red papules on steroids if severe extensor surfaces, trunk Pruritic folliculitis of Rare Small red papules, sterile


Obstentrics_Williams

Obstentrics_Williams. Pruritic folliculitis of Rare Small red papules, sterile Pemphigoid Rare Erythematous pruritic papules, Preterm birth, fetal gestationis plaques, vesicles, and bullae; growth restriction, abdomen often with umbilical transient neonatal involvement, extremities lesions this is mild placental insuiciency that stems from IgG and resolution is protracted, and disease may be exacerbated during complement deposition along the amnionic basement memmenses or by oral contraceptives (Semkova, 2009). brane (Huilaja, 2013). Accordingly, antepartum surveillance of afected pregnancies is reasonable.


Obstentrics_Williams

Obstentrics_Williams. In 5 to 10 percent of cases, IgG antibodies passively transfer Before bullae form, these lesions may resemble pruritic urtifrom the mother to cause similar skin lesions in the newborn carial papules and plaques of pregnancy. Other diagnoses (Erickson, 2002). hese eruptions in the neonate require only include pustular psoriasis, dermatitis herpetiformis, erythema wound care and clear spontaneously within a few weeks as the multiforme, linear 19A bullous dermatosis, urticaria, allergic passively acquired IgG levels decline. Slowly following contact dermatitis, bullous pemphigoid, and atopic eruption maternal lesions resolve without scarring, and most women are of pregnancy (LipozenCic, 2012). Drug-induced blistering disease-free after 6 months (Jenkins, 1999). In some, however, syndromes must also be excluded as some are life-threatening,


Obstentrics_Williams

Obstentrics_Williams. FIGURE 62-1 Pemphigoid gestation is. A. Abdominal plaques classically involve the umbilicus. B. Blistered lesions on the wrist and forearm. (Used with permission from Dr. Kara Ehlers.) for example, Stevens-Johnson syndrome and toxic epidermal necrolysis (Stern, 2012). Skin biopsy and serum antibody assays are informative. Immunofluorescent staining of a skin punch biopsy sample is the gold standard, and C3 complement and sometimes IgC are seen deposited along the basement membrane between the epidermis and the dermis (Katz, 1976). Also, in many cases, circulating IgC antibodies against collagen V1I can be detected in maternal serum (Powell, 2005; Sitaru, 2004).


Obstentrics_Williams

Obstentrics_Williams. Pruritus can be severe. Early in its course, topical highpotency corticosteroids and oral antihistamines may be efective. Oral prednisone, 0.5 to 1 mg/kg daily gradually tapered to a maintenance dose, may be needed for relief and also for inhibition of new lesions. Plasmapheresis, high-dose intravenous immunoglobulin (IVIC) therapy, or cyclosporine has been used in intractable cases (Huilaja, 2015; Ko, 2014; Van de Wiel, 1980).


Obstentrics_Williams

Obstentrics_Williams. Plaques of Pregnancy his relatively common pregnancy-speciic dermatosis is characterized by its benign efects on pregnancy and by intensely pruritic 1-to 2-mm erythematous papules that coalesce to form urticarial plaques. Also known as poymorphic eruption of pregnancy, PUPPP usually appears late in pregnancy (Rudolph, 2005). Rarely, postpartum onset has been described (Park, 2013). he rash afects the abdomen and proximal thighs in 97 percent of women (Fig. 62-2). Lesions often initially form within striae but show periumbilical sparing. The face, palms, and soles also are rarely involved (High, 2005). It is more frequent in white and nulliparous women, those with multifetal gestation, and those carrying a male fetus (Regnier, 2008). PUPPP seldom recurs in subsequent pregnancies (Ahmadi, 2005). Its cause is unknown, but an autoimmune basis is not implicated (Lawley, 1979).


Obstentrics_Williams

Obstentrics_Williams. PUPPP may be compared with several skin eruptions. Some include contact dermatitis, drug eruption, viral exanthem, insect bites, scabies infestation, pityriasis rosea, and the other pregnancy-speciic dermatoses. It also may appear similar to early PC that has not yet blistered. In unclear cases, skin biopsy and negative serum collagen V1I antibody levels help to differentiate the two. Pruritus will usually respond to treatment with oral antihistamines, skin emollients, and topical corticosteroids. A few women will need systemic corticosteroids to relieve severe itching (Scheinfeld, 2008). FIGURE 62-2 Pruritic urticarial papules and plaques of pregnancy (PUPPP) shows sma" papules on the buttock and proximal thigh and within abdominal striae. PUPPP usually resolves within several days following delivery and leaves no scarring. In 15 to 20 percent of women, however, symptoms persist for 2 to 4 weeks postpartum (Vaughan Jones, 1999).


Obstentrics_Williams

Obstentrics_Williams. PUPPP usually resolves within several days following delivery and leaves no scarring. In 15 to 20 percent of women, however, symptoms persist for 2 to 4 weeks postpartum (Vaughan Jones, 1999). • Atopic Eruption of Pregnancy his umbrella term encompasses three conditions previously considered separate: eczema in pregnancy, prurigo of pregnancy, and pruritic folliculitis of pregnancy (Ambros-Rudolph, 2006). Two thirds of women with atopic eruption have widespread eczematous changes, whereas the other third have papular lesions (American Academy of Dermatology, 201r1). As a group, these pose no risk to the fetus. Diagnosis is greatly aided by a history of atopy and by rash characteristics.


Obstentrics_Williams

Obstentrics_Williams. Eczema in pregnany has the appearance of traditional eczema but with a pregnancy onset. It is the most common pregnancy-specific dermatosis, and afected skin shows dry, thickened, scaly, red patches involving extremity lexures, nipples, neck, and face. In contrast, prurigo of pregnancy, also known as prurigo gestationis) is characterized by 5-to 10-mm, itchy, erythematous papules or nodules commonly found on the extensor surfaces and trunk. Last, pruritic olliculitis of pregnancy is rare and notable for small, erythematous follicular papules and sterile pustules predominantly on the trunk. Onset for all is during the second or third trimester, although eczema in pregnancy may develop earlier than the other two. All lesions commonly resolve with delivery, but may persist for up to 3 months postpartum. Recurrence with subsequent pregnancies is variable but common.


Obstentrics_Williams

Obstentrics_Williams. Diagnosis is one of exclusion. Serum bile acid levels are elevated but not greater than concentrations expected for normal pregnancy, and aminotransferase levels are normal. Serology specific for PC is negative. Many women with eczema of pregnancy have elevated serum IgE levels, which are not seen with the two other AEP dermatoses (Ambros-Rudolph, 201r1). For all three manifestations, skin lesions and pruritus are usually controlled with low-or moderate-potency topical corticosteroids and oral antihistamines. For severe eczema, second-line agents include short-course ultrapotent topical corticosteroids. In some cases, however, an oral corticosteroid, narrow-band ultraviolet B, or cyclosporine is required (Lehrhof, 2013). pregnancy. Some of those chronic conditions are considered here.


Obstentrics_Williams

Obstentrics_Williams. his common chronic dermatosis is unpredictably afected by pregnancy and, if necessary, is treated with benzoyl peroxide alone or coupled with either topical erythromycin or topical clindamycin (Zaenglein, 2016). In these combinations, benzoyl peroxide minimizes Propionibacterium acnes drug resistance. Azelaic acid is another comedolytic agent, which is category B. Topical salicylic acid is category C, but amounts in over-the-counter products are considered safe (Murase, 2014). Topical retinoids, which include tretinoin and adapalene, also appear safe, are category C drugs, but are probably best avoided during pregnancy, especially during the irst trimester (Kaplan, 2015; Panchaud, 2012). Topical tazarotene is contraindicated. For more severe cases, oral antibiotics that include erythromycin, azithromycin, cephalexin, or amoxicillin may be coupled with benzoyl peroxide. Systemic antibiotics are ideally delayed until the second trimester, and therapy duration limited to 4 to 6 weeks


Obstentrics_Williams

Obstentrics_Williams. azithromycin, cephalexin, or amoxicillin may be coupled with benzoyl peroxide. Systemic antibiotics are ideally delayed until the second trimester, and therapy duration limited to 4 to 6 weeks (Chien, 2016).


Obstentrics_Williams

Obstentrics_Williams. his chronic dermatosis also has a variable course during pregnancy, however, postpartum lares are common (Oumeish, 2006). Emollients alone are given initially, and low-or moderate-potency topical corticosteroids can be added. In resistant cases, restrained use of high-potency or ultrapotent corticosteroids appears safe in the second and third trimesters. Ultraviolet B phototherapy can be used as a second-line option. Last, cyclosporine, systemic corticosteroids, or tumor necrosis factor (TNF)-a antagonists that include adalimumab, etanercept, and inliximab are third-tier agents for pregnancy (Bae, 2012). Overall, data do not support an increased risk of adverse pregnancy outcomes with psoriasis (Bobotsis, 2016). With severe disease, a small increased risk for low-birthweight neonates was found by some (Lima, 2012; Yang, 2011). Also, in general, psoriatic patients have higher associated rates of depression (Bandoli, 2017; Cohen, 2016).


Obstentrics_Williams

Obstentrics_Williams. Psoriasis is most commonly of the chronic plaque variety. In contrast, with generalized pustuar psoriasis of pregnancy, severe systemic symptoms may develop. Formerly called impetigo herpetiformis, this rare pustular form has erythematous, sometimes pruritic plaques ringed by sterile pustules that enlarge and then crust (Fig. 62-3). Lesions initially involve intertriginous areas but may spread to the torso, extremities, and oral mucosa. Comorbid constitutional symptoms are common. Laboratory testing may reveal hypocalcemia, elevated erythrocte sedimentation rate, leukocytosis, and hypoalbuminemia (Lehrhof, 2013). Extensive lesions can lead to sepsis from secondary infection and to massive fluid loss with hypovolemia and placental insuiciency. First-line treatment is with oral prednisone, cyclosporine, infliximab, topical corticosteroids, or topical calcipotriene (Robinson, 2012). Phototherapy is a second-line option. For secondary infections, intravenous antibiotics are added (Huang,


Obstentrics_Williams

Obstentrics_Williams. cyclosporine, infliximab, topical corticosteroids, or topical calcipotriene (Robinson, 2012). Phototherapy is a second-line option. For secondary infections, intravenous antibiotics are added (Huang, 2011). Pustular psoriasis typically resolves quickly in the puerperium, but recurrences have been reported in subsequent pregnancies and with menstruation or oral contraceptive use (Roth, 2011).


Obstentrics_Williams

Obstentrics_Williams. his skin condition represents inflammation of subcutaneous fat associated with numerous disorders, including pregnancy. Other triggers are infections, sarcoidosis, drugs, Beh:et syndrome, inlammatory bowel disease, or a malignancy (Mert, 2007; Papagrigoraki, 2010). Characteristically, 1-to 6-cm tender, red, warm nodules and plaques develop rapidly on the extensor surface of the legs and arms. Within a few days, lesions flatten and undergo the color evolution of a bruise-from dark red and purple to yellow green. Constitutional symptoms may also be present. Initial evaluation and treatment focuses on the underlying etiology. Symptoms spontaneously resolve in 1 to 6 weeks without scarring but may leave residual hyperpigmentation (Acosta, 2013). his lesion is frequently seen in pregnancy (Fig. 62-4). Poorly named, pyogenic granuloma is actually a lobular capillary hemangioma commonly forming on the mouth or hand in response to low-grade local irritation or traumatic injury. hey grow


Obstentrics_Williams

Obstentrics_Williams. FIGURE 62-3 Generalized pustular psoriasis of pregnancy displays FIGURE 62-4 Pyogenic granuloma is characterized grossly by a erythematous, sometimes pruritic plaques ringed by sterile pustules lobulated red growth on a pedunculated or sessile base. With minithat enlarge and then form a scaling crust. (Used with permission mal trauma, these vascular lesions bleed easily. (Used with permisfrom Dr. Paul Slocum.) sion from Dr. Abel Moron.) quickly and bleed with minimal provocation. Active bleeding can be controlled with pressure and application of a silver nitrate stick or Monsel paste (ferric subsulfate). These growths often resolve within months postpartum. But with a symptomatic antepartum growth, a persistent postpartum lesion, or with an unclear diagnosis, excision can be done using suture and scalpel, electrosurgical curettage, laser photocoagulation, or cryotherapy. Oral lesions are best referred to oral health-care specialists.


Obstentrics_Williams

Obstentrics_Williams. These lesions are typiied by benign cutaneous neuroibromas, cafe-au-lait spots, axillary and inguinal freckling, benign nodules of the iris (Lisch nodules), and optic nerve gliomas. Neuroibromas may increase in size and number during pregnancy (Cesaretti, 2013; Dugof, 1996). With the more common neuroibromatosis type 1, higher rates of preclampsia and preterm birth complicate pregnancy (Leppavirta, 2017; Terry, 2013). With neurofibromatosis type 2, some evidence suggests a risk for preeclampsia (Terry, 2015). Prenatal genetic diagnosis is available for both types (Merker, 2015; Spits, 2007). Rosacea ulminans is also known as pyoderma aciale. It is rare and characterized by facial pustules and coalescing draining sinuses. Topical or oral antimicrobials are primary treatment, although surgical drainage and corticosteroids have also been used (F uentelsaz, 2011; Jarrett, 2010).


Obstentrics_Williams

Obstentrics_Williams. Hidradenitis suppurativa is said to improve with pregnancy, but in our experiences, it is not appreciably changed. Twice daily topically applied I-percent clindamycin gel for 12 weeks aims to prevent new lesions. This can be supplemented by 7-to 10-day courses of oral amoxicillin plus clavulanic acid or oral clindamycin to reduce lesion progression (Margesson, 2014). Other options are reviewed by Perng and coworkers (2017). Other skin conditions that are discussed elsewhere in this book include hirsutism and melanoma (Chap. 63, p. 1203), cutaneous lupus (Chap. 59, p. 1140), hyperpigmentation (Chap. 4, p. 53), and skin lesions seen with infections (Chaps. 64 and 65).


Obstentrics_Williams

Obstentrics_Williams. Local skin care, oral antihistamines, and topical corticosteroids are commonly used for many dermatoses. Oral antihistamines are given for pruritus. Suitable options include irst-generation agents such s diphenhydramine (Benadryl), 25 to 50 mg every 6 hours, or chlorpheniramine (Chlor-Trimeton), 4 mg every 6 hours. Second-generation agents-Ioratadine (Claritin) 10 mg daily or cetirizine (Zyrtec) 5 or 10 mg daily-may produce less sedation and are also pregnancy category B.


Obstentrics_Williams

Obstentrics_Williams. Hundreds of topical corticosteroid preparations are available, and in the United States, these are categorized by potency into seven groups. For initial treatment of dermatological disorders, low-or moderate-potency agents are preferred. Low-potency agents include those in groups 6 and 7, such as I-percent hydrocortisone or 0.05-percent desonide (DesOwen). Moderate-potency drugs are in groups 5, 4, and 3-such as O.I-percent triamcinolone acetonide (Aristocort) or O.I-percent mometasone furoate (Elocon). High-potency medications are in group 2, such as 0.05-percent betamethasone dipropionate (Diprolene). Ultrapotent agents in group 1, such as 0.05-percent clobetasol propionate (Temovate), are best reserved for refractory disorders and used for only 2 to 4 weeks on small surface areas.


Obstentrics_Williams

Obstentrics_Williams. Mild and moderate strengths are not associated with adverse pregnancy outcomes, whereas high-and ultrapotent agents pose a small risk for fetal-growth restriction with large cumulative doses (Chi, 2013, 2015). Even then, this risk is less than that with systemic corticosteroids. Importantly, with any topical agent, factors that increase systemic absorption include a large surface area treated, compromised epidermal barrier, occlusive dressings, prolonged treatment duration, and coadministration of topical agents that increase absorption.


Obstentrics_Williams

Obstentrics_Williams. The list of other agents used for dermatological conditions is extensive. For use in pregnancy and lactation, Murase (2014) and Butler (2014) have compiled tables and evidencebased descriptions of most. Notable therapeutic agents to avoid during pregnancy include methotrexate, psoralen plus ultraviolet A, mycophenolate mofetil, podophyllin, and systemic retinoids. hese are discussed in more detail in Chapter 12. Bacterial infections are a potential secondary complication of skin disorders and are treated promptly with oral antimicrobial agents with gram-positive coverage. Acosta A, Haver MC, Kelly B: Etiology and therapeutic management of erythema nodosum during pregnancy: an update. Am J Clin Dermatol 14(3):215,t2013 Ahmadi S, Powell FC: Pruritic urticarial papules and plaques of pregnancy: current status. Australas J Dermatol 46(2):53, 2005


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Obstentrics_Williams. Ahmadi S, Powell FC: Pruritic urticarial papules and plaques of pregnancy: current status. Australas J Dermatol 46(2):53, 2005 Al-Saif F, Elisa A, Al-Homidy A, et al: Retrospective analysis of pemphigoid gestationis in 32 Saudi patients-clinicopathological features and a literature review. J Reprod Immunol 11t6:42,t20t16 Ambros-Rudolph CM: Dermatoses of pregnancy-clues to diagnosis, fetal risk and therapy. Ann Dermatol23(3):265, 2011 Ambros-Rudolph CM, Mullegger R, Vaughan-Jones SA, et al: The specific dermatoses of pregnancy revisited and reclassified: results of a retrospective two-center study on 505 pregnant patients. J Am Acad Dermatol 54:395, 2006 American Academy of Dermatology: Learning module: dermatoses in pregnancy. 2011t. Available at: https://www.aad.org/education/basic-dermcurricul um/ suggested -order-of-modules/ dermatoses-in -p regnancy. Accessed May 17, 2016


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Obstentrics_Williams. Bae YS, Van Voorhees AS, Hsu S, et al: Review of treatment options for psoriasis in pregnant or lactating women: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol67(3):459, 2012 Bandoli G, Chambers CD: Autoimmune conditions and comorbid depression in pregnancy: examining the risk of preterm birth and preeclampsia. J Perinatolt37(lO):1082,t2017 Bobotsis R, Gulliver P, Monaghan K, et al: Psoriasis and adverse pregnancy outcomes: a systematic review of observational studies. Br J Dermatol 175(3):464,t2016 Butler DC, Heller MM, Murase JE: Safety of dermatologic medications in pregnancy and lactation: Part II. Lactation. J Am Acad Dermatol 70(3):417.e1, 2014 Cesaretti C, Melloni G, Quagliarini D: Neuroibromatosis type 1 and pregnancy: maternal complications and attitudes about prenatal diagnosis. m J Med Genet A 161A (2):386, 2013


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Obstentrics_Williams. Cesaretti C, Melloni G, Quagliarini D: Neuroibromatosis type 1 and pregnancy: maternal complications and attitudes about prenatal diagnosis. m J Med Genet A 161A (2):386, 2013 Chander R, Garg T, Kakkar S, et al: Speciic pregnancy dermatoses in 1430 females from Northern India. J Dermatol Case Rep 5(4):69, 201t1 Chao TT, Sheield JS: Primary dermatologic indings with early-onset intrahepatic cholestasis of pregnancy. Obstet Gynecol 117:456, 2011 Chi CC, Wang SH, Charles-Holmes R, et al: Pemphigoid gestationis: early onset and blister formations are associated with adverse pregnancy outcomes. Br] DermatoIt160(6):1222, 2009 Chi CC, Wang SH, Mayon-White R: Pregnancy outcomes after maternal exposure to topical corticosteroids: a UK population-based cohort study. ]AMA DermatoIt149(11):1274, 2013 Chi CC, Wang SH, Wojnarowska F, et al: Safety of topical corticosteroids in pregnancy. Cochrane Database Syst Rev 10:CD007346, 2015


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Obstentrics_Williams. Chi CC, Wang SH, Wojnarowska F, et al: Safety of topical corticosteroids in pregnancy. Cochrane Database Syst Rev 10:CD007346, 2015 Chien AL, Qi], Rainer B, et al: Treatment of acne in pregnancy.] Am Board Fam Med 29(2):254,t2016 Cohen BE, Martires K], Ho RS: Psoriasis and the risk of depression in the US population: national health and nutrition examination survey 2009-2012. ]AMA Dermatol 3,t2016 Dugof L, Sujansky E: Neuroibromatosis type 1 and pregnancy. Am ] Med Genet 66(1):7, 1996 Engineer L, Bhol K, Ahmed AR: Pemphigoid gestationis: a review. Am ] Obstet GynecoIt183(2):483, 2000 Erickson NI, Ellis L: Neonatal rash due to herpes gestation is. N Englt] Med 347(9):660, 2002 Fuentelsaz V, Ara M, Corredera C, et al: Rosacea fulminans in pregnancy: successful treatment with azithromycin. Clin Exp DermaroI36(6):674, 2011


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Obstentrics_Williams. High WA, Hoang MP, Miller MD: Pruritic urticarial papules and plaques of pregnancy with unusual and extensive palmoplantar involvement. Obstet Gynecol 105:1261,t2005 Huang H, Chen P, Liang CC, et al: Impetigo herpetiform is with gestational hypertension: a case report and literature review. Dermatology 222(3):221, 2011 Huilaja L, Makikallio K, Hannula-]ouppi K, et al: Cyclosporine treatment in severe gestational pemphigoid. Acta Derm Venereol 95(5):593, 2015 Huilaja L, Makikallio K, Sormunen R, et al: Gestational pemphigoid: placental morphology and function. Acta Derm Venereol 93(1):33, 2013 Jarrett R, Gonsalves R, Anstey AV: Difering obstetric outcomes of rosacea fulminans in pregnancy: report of three cases with review of pathogenesis and management. Clin Exp Dermatol 35(8):888, 2010 Jenkins E, Hern S, Black MM: Clinical features and management of 87 patients with pemphigoid gestationis. Clin Exp DermatoI24(4):255, 1999


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Obstentrics_Williams. Jenkins E, Hern S, Black MM: Clinical features and management of 87 patients with pemphigoid gestationis. Clin Exp DermatoI24(4):255, 1999 Kaplan YC, Ozsarfati ], Etwel F, et al: Pregnancy outcomes following irsttrimester exposure to topical retinoids: a systematic review and meta-analysis. Br] DermatoIt173(5):1132, 2015 Katz SI, Hertz KC, Yaoita H: Herpes gestationis. Immunopathology and characterization of the HG factor.t] Clin Invest 57(6):1434,t1976 Kelly SE, Bhogal BS, Wojnarowska F, et al: Expression of a pemphigoid gestationisrelated antigen by human placenta. Br] DermatoIt118:605, 1988 Ko B], Whang KU: Intravenous immunoglobulin therapy for persistent pemphigoid gestationis with steroid induced iatrogenic Cushing's syndrome. Ann DermatoIt26(5):661, 2014 Lawley T], Hertz KC, Wade TR, et al: Pruritic urticarial papules and plaques of pregnancy. ]AMA 241 (16): 1696, 1979


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Obstentrics_Williams. Lawley T], Hertz KC, Wade TR, et al: Pruritic urticarial papules and plaques of pregnancy. ]AMA 241 (16): 1696, 1979 Lawley T], Stingl G, Katz SI: Fetal and maternal risk factors in herpes gestationis. Arch DermatoIt114(4):552, 1978 Lehrhof S, Pomeranz MK: Specific dermatoses of pregnancy and their treatment. Dermatol her 26(4):274,t2013 Leppavirtat], Kallionpaa A, Uusitalo E, et al: he pregnancy in neuroibromatosis 1: A retrospective register-based total population study. Amt] Med Genet A 173(10):2641,t2017 Lima XT, ]anakiraman V, Hughes MD, et al: The impact of psoriasis on pregnancy outcomes.t] Invest Dermatol 132(1):85,t2012 Lipozencic ], Ljubojevic S, Bukvic-Mokos Z: Pemphigoid gestationis. Clin DermatoIt30(1):51,t2012 Margesson L], Danby FW: Hidradenitis suppurativa. Best Pract Res Clin Obstet GynaecoIt28(7):1013, 2014


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Obstentrics_Williams. Margesson L], Danby FW: Hidradenitis suppurativa. Best Pract Res Clin Obstet GynaecoIt28(7):1013, 2014 Matsumoto N, Osada M, Kaneko K, et al: Pemphigoid gestation is after sponta neous expulsion of a massive complete hydatidiform mole. Case Rep Obstet 268,t2013 Merker VL, Murphy TP, Hughes ]B, et al: Outcomes of preimplantation genetic diagnosis in neuroibromatosis type 1. Ferti! Steriltl03(3):76t1, 20t15 Men A, Kumbasar H, Ozaras R, et al: Erythema nodosum: an evaluation of 100 cases. Clin Exp Rheumatol 25(4):563, 200 Murase ]E, Heller MM, Buder DC: Safety of dermatologic medications in pregnancy and lactation: part r. Pregnancy.] Am Acad Dermatol 70(3):40 l.e1, 2014 Oumeish OY, AI-Fouzan A W: Miscellaneous diseases afected by pregnancy. Clin Dermatol 24: 113, 2006 Panchaud A, Csajka C, Merlob P, et al: Pregnancy outcome following exposure to topical retinoids: a multicenter prospective study. ] Clin Pharmacol 52(12):1844,t2012


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Obstentrics_Williams. Clin Dermatol 24: 113, 2006 Panchaud A, Csajka C, Merlob P, et al: Pregnancy outcome following exposure to topical retinoids: a multicenter prospective study. ] Clin Pharmacol 52(12):1844,t2012 Papagrigoraki A, Gisondi P, Rosina P, et al: Erythema nodosum: etiological factors and relapses in a retrospective cohort study. Eur ] Dermatol 3,t2010 Park SY, Kim ]H, Lee WS: Pruritic urticarial papules and plaques of pregnancy with unique distribution developing in postpartum period. Ann Dermatol 25(4):506,t2013 Perng P, Zampella]G, Okoye GA: Management of hidradenitis suppurativa in pregnancy.] Am Acad Dermatol 76(5):979, 2017 Powell M, Sakuma-Oyama Y, Oyama N, et al: Usefulness of BP180 NC16a enzyme-linked immunosorbent assay in the serodiagnosis of pemphigoid gestationis and in diferentiating between pemphigoid gestationis and pruritic urticarial papules and plaques of pregnancy. Arch Dermatol 141(6): 705, 2005


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Obstentrics_Williams. Regnier S, Fermand V, Levy P, et al: A case-control study of polymorphic eruption of pregnancy. ] Am Acad Dermatol 58 (1):63, 2008 Robinson A, Van Voorhees AS, Hsu S, et al: Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation. ] Am Acad Dermatol 67(2):279, 2012 Roth MM: Pregnancy dermatoses: diagnosis, management, and controversies. Amt] Clin Dermatol 12(1):25,t2011 Rudolph CM, AI-Fares S, Vaughan-Jones SA, et al: Polymorphic eruption of pregnancy: clinicopathology and potential trigger factors in 181 patients. Br ] Dermatol 154:54,t2005 Scheinfeld N: Pruritic urticarial papules and plaques of pregnancy wholly abated with one week twice daily application of fluticasone propionate lotion: a case report and review of the literature. Dermatol Online 14(11):4,2008


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Obstentrics_Williams. Segal 0, Holcberg G, Sapir 0, et al: Neuroibromatosis in pregnancy. Maternal and perinatal outcome. Eur] Obstet Gynecol Reprod Bioi 84(1):59, 1999 Semkova K, Black M: Pemphigoid gestationis: current insights into pathogenesis and treatment. Eur] Obstet Gynecol Reprod Bioi 145(2):138, 2009 Shimanovich 1, Skrobek C, Rose C, et al: Pemphigoid gestationis with predominant involvement of oral mucous membranes and IgA autoantibodies targeting the C-terminus ofBP180.] Am Acad DermaroI47:780, 2002 Shornick]K, Black MM: Fetal risks in herpes gestationis. ] Am Acad Dermatol 26:63, 1992 Shornick ]K, Meek T], Nesbitt LT, et al: Herpes gestationis in blacks. Arch DermatoIt120(4):511,t1984 Sitaru C, Powell], Messer G, et al: Immunoblotting and enzyme-linked immunosorbent assay for the diagnosis of pemphigoid gestationis. Obstet Gynecol 103(4):757,t2004 Spits C, De Rycke M, Van Ranst N, et al: Preimplantation genetic diagnosis for cancer predisposition syndromes. Prenat Diagn 27(5):44 ,t2007


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Obstentrics_Williams. Spits C, De Rycke M, Van Ranst N, et al: Preimplantation genetic diagnosis for cancer predisposition syndromes. Prenat Diagn 27(5):44 ,t2007 Stern RS: Exanthematous drug eruptions. N Engl] Med 366:2492, 2012 Takatsuka Y, Komine \1, Ohtsuki M: Pemphigoid gestation is with a complete hydatidiform mole.] DermatoI39(5):474, 2012 Tani N, Kimura Y, Koga H, et al: Clinical and immunological proiles of 25 patients with pemphigoid gestationis. Br] DermatoIt172(1):120, 2015 Terry AR, Barker FG 2nd, Lefert L, et al: Neuroibromatosis type 1 and pregnancy complications: a population-based study. Am ] Obstet Gynecol 209(1) :46.e1, 2013 Terry AR, Merker L, Barker FG 2nd, et al: Pregnancy complications in women with rare tumor suppressor syndromes afecting central and peripheral nervous system. Amt] Obstet GynecoIt213(1):108, 2015 Van de Wiel A, Hart HC, Flinterman], et al: Plasma exchange in herpes gestationis. BM] 281: 1041, 1980


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Obstentrics_Williams. Van de Wiel A, Hart HC, Flinterman], et al: Plasma exchange in herpes gestationis. BM] 281: 1041, 1980 Vaughan Jones SA, Hern S, Nelson-Piercy C, et al: A prospective study of 200 women with dermatoses of pregnancy correlating clinical indings with hormonal and immunopathological proiles. Br J Dermatol 1, 1999 iksrr:im Shemer E, Marschall HU, Ludvigsson ]F, et al: Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: a 12-year population-based cohort study. B]OG ,t2012 Yang YW, Chen CS, Chen H, et al: Psoriasis and pregnancy outcomes: a nationwide population-based study.t] Am Acad Dermatol 64(1):71, 201t1 Zaenglein AL, Pathy AL, Schlosser B], et al: Guidelines of care for the manage ment of acne vulgaris.] Am Acad Dermatol 74(5):945, 2016 CANCER THERAPY IN PREGNANCY .i........i....... 1191 REPRODUCTIVE TRACT NEOPLASMS.. . . . . . . . . . . . .. 1192


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Obstentrics_Williams. CANCER THERAPY IN PREGNANCY .i........i....... 1191 REPRODUCTIVE TRACT NEOPLASMS.. . . . . . . . . . . . .. 1192 BREAST CARCINOMA. . . . . . . . . . . . . . . . . . . . . . . . . .. 1200 THYROID CANCER.. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1201 LYMPHOMAS.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1202 MALIGNANT MELANOMA. . . . . . . . . . . . . . . . . . . . . .. 1203 GASTROINTESTINAL TRACT . . . . . . . . . . . .. 1204 MISCELLANEOUS TUMORS. . . . . . . . . . . . . . . . . . . . .. 1204 of the more frequent ones are shown in Figure 63-1. Breast cancer is found in 1 in 5000 pregnancies, thyroid-1 in 7000, and cervical-1 in 8500 (Smith, 2003). These, along with lymphoma and melanoma, account for 65 percent of malignancy cases in pregnancy (Eibye, 2013). For some cancers-ovary, endometrium, and breast-evidence suggests that high parity is protective (Hognas, 2014).


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Obstentrics_Williams. During pregnancy, cancer management poses unique problems related to fetal concerns, and treatment must be individualized. Considerations include the type and stage of malignancy, the desire for pregnancy continuation, and inherent risks associated with modiying or delaying cancer treatment. Any excessive enlargement of the abdomen or the appearance of pressure symptoms should always lead one to make a carul examination, and in not a ew cases a tumour will be ound occupying the pelvic caviy. In rare instances malignant tumours of the rectum may so obstruct the pelvic canal as to render caesarean section imperative. -J. Whitridge Williams (1903) Any neoplasm can complicate pregnancy, and as written by Williams, physical examination often suggests the diagnosis. Current imaging also allows a greater number of these to be identiied antepartum. Most encountered neoplasms are benign, and uterine leiomyomas and ovarian cysts are the most frequent.


Obstentrics_Williams

Obstentrics_Williams. Cancer has an incidence approximating 1 per 1000 pregnancies (Parazzini, 2017; Salani, 2014). One third are diagnosed prenatally, and the others within 12 months of delivery. Some FIGURE 63-1 Proportion of malignancies during pregnancy and within 12 months of delivery in 4.85 million women from the California Cancer Registry. GI = gastrointestinal. (Data from Smith, 2003.) diagnosis, staging, or therapy. Fortunately, most procedures that do not interfere with the reproductive tract are well toler ated by both mother and fetus (Chap. 46, p. 901). Although many operations have classically been deferred until after 12 to 14 weeks' gestation to minimize miscarriage risks, this probably is not necessary. We are of the opinion that surgery should be performed regardless of gestational age if maternal well-being is imperiled.


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Obstentrics_Williams. Both pregnancy and malignancy are risk factors for venous thromboembolism (VTE). In one study, Bleau and coworkers (2016) reported a higher risk ofVTE in gravidas with myeloid leukemia, Hodgkin disease, cervical cancer, and ovarian cancer compared with that in pregnant women without a malignancy. The risk was not increased in those with brain or thyroid cancer, melanoma, or lymphoid leukemia. That said, current guidelines ing surgeries for cancer. hus, depending on the complexity of the planned procedure, it seems reasonable to use prophylactic low-molecular-weight heparin combined with elastic stockings and/or intermittent pneumatic compression as described in Chapter 52 (p. 1019).


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Obstentrics_Williams. Sonography is a preferred imaging tool during pregnancy. Even so, according to the American College of Obstetricians and Gynecologists (2017a), most diagnostic radiographic procedures deliver very low x-ray doses and should not be delayed if they would directly afect therapy (Chap. 46, p. 906). Magnetic resonance (MR) imaging can safely be performed in any trimester, but delay until after the irst trimester may lower potential risks. Gadolinium should not be used in the irst trimester and should be used later in pregnancy only when the beneits overwhelmingly outweigh the risks (American College of Radiology, 2016; Kanal, 2013). Computed tomography (CT) is less often selected due to ionizing radiation, and procedure-related doses are listed in Chapter 46 (p. 907). Accordingly, CT is used in pregnancy most often to evaluate acute concerns that include pulmonary embolism, bowel or renal obstruction, and acute neurological events. To enhance CT, oral and intravenous contrasts may be


Obstentrics_Williams

Obstentrics_Williams. in pregnancy most often to evaluate acute concerns that include pulmonary embolism, bowel or renal obstruction, and acute neurological events. To enhance CT, oral and intravenous contrasts may be added. hese lack known fetal harm, and postpartum breastfeeding need not be interrupted. Last, some radioisotopes are relatively safe in pregnancy and are listed in Table 46-8 (p. 909).


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Obstentrics_Williams. herapeutic radiation often results in signiicant fetal exposure depending on the dose, tumor location, field size, and gestational age. Potential adverse efects include fetal malformation, intellectual disability, growth restriction, sterility, and carcinogenesis (Brent, 1999; Stovall, 1995). In the 2 weeks following fertilization, exposure typically leads to chromosomal damage and embryonic death. he next most susceptible period is during organogenesis in weeks 2 through 8, and exposure can cause malformation. These might develop above a threshold dose of 0.1 to 0.2 Gy. During weeks 8 through 25, the fetal central nervous system is especially vulnerable. The threshold dose for intellectual disability at 8 to 15 weeks' gestation approximates 0.06 Gy, and at 16 to 25 weeks it is about 0.25 Gy (Kal, 2005; Otake, 1996). After 25 weeks' gestation, susceptibility is less, although no gestational age is considered safe for therapeutic radiation exposure. hus, radiotherapy to the maternal


Obstentrics_Williams

Obstentrics_Williams. Gy (Kal, 2005; Otake, 1996). After 25 weeks' gestation, susceptibility is less, although no gestational age is considered safe for therapeutic radiation exposure. hus, radiotherapy to the maternal abdomen is contraindicated. With some head and neck cancers, however, radiotherapy to supradiaphragmatic areas can be used relatively safely with abdominal shielding of the fetus (Amant, 2015a).


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Obstentrics_Williams. Various antineoplastic drugs may be given for primary treatment or for adjunctive therapy. Although chemotherapy often improves long-term maternal outcomes, many are reluctant to employ it during pregnancy. Concerns for the fetus include malformations, growth restriction, intellectual disability, and the risk of future childhood malignancies. Risks are dependent primarily on fetal age at exposure, and most agents are potentially detrimental in the irst trimester during organogenesis. Indeed, in one review, 14 percent of major malformations were attributable to irst-trimester exposure to cytotoxic drugs (National Toxicology Program, 2013).


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Obstentrics_Williams. Ater the first trimester, most antineoplastic drugs are without immediate obvious adverse fetal sequelae (Abdel-Hady, 2012; Vercruysse, 2016). Similarly, late mutagenic efects appear limited (Amant, 2015b; Cardonick, 2015). Although not always practicable, some recommend that chemotherapy be withheld in the 3 weeks before expected delivery because neutropenia or pancytopenia might cause undue risk for maternal infection or hemorrhage. Another concern is that neonatal hepatic and renal clearance of chemotherapy metabolites is limited (Ko, 2011). For these reasons, most cytotoxic chemotherapy agents are contraindicated with breastfeeding (Pistilli, 2013).


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Obstentrics_Williams. Drugs designed to stimulate hemopoiesis are commonly used with cancer treatments. Some of these include the granulocyte colony-stimulating factors filgrastim (Neupogen) and pegilgrastim (Neulasta). If required in pregnancy, limited data support the safety of these agents (Boxer, 2015). Red blood cells can be stimulated by erythropoietin alfa (Procrit), which from case reports also appears safe in pregnancy (Sienas, 2013). However, maternal hypertension is a known potential risk. he two main types of targeted therapy are monoclonal antibodies and small molecule inhibitors. Both block the actions of specific enzymes, proteins, or other molecules involved in cancer cell growth. hese drugs are designed to treat an everexpanding list of cancers, and some are described in later discussions of specific tumors. Most of these compounds are labeled by the Food and Drug Administration (FDA) as class D, and data are limited regarding their pregnancy or breastfeeding efects.


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Obstentrics_Williams. D, and data are limited regarding their pregnancy or breastfeeding efects. Many of these drugs target tyrosine kinase, an important enzyme that regulates signaling pathways involved with cell division, diferentiation, and apoptosis. With irst-trimester use, embryo toxicity or teratogenicity has been attributed to these. Thus, this speciic group of targeted agents is considered for use in pregnancy only if the potential beneit to the pregnant woman justifies the potential risk to the fetus (Lodish, 2013). Of other agents, the monoclonal antibody trastuzumab (Herceptin) inhibits the human epidermal growth factor receptor type 2 (HER2), which some breast cancers express. Although not teratogenic, its use in the second and third trimesters is associated with oligohydramnios, which appears to be reversible upon stopping the drug (Sarno, 2013; Zagouri, 2013b). Because of sparse available data, other HER2 inhibitors are best avoided in pregnancy (Lambertini, 2015).


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Obstentrics_Williams. Fertility may be diminished after chemotherapy or radiotherapy. Counseling ideally takes place before cancer treatment, and guidelines for this have been developed (American Society for Reproductive Medicine, 2013a; Lambertini, 2016; Loren, 2013; Peccatori, 2013). Prior to therapy, cryopreservation of embryos or of oocytes is a recognized fertility-preserving option (American Society for Reproductive Medicine, 2013b,c). Surgical transposition of the ovaries can be considered if pelvic radiation is planned. For this, ovaries and their intact primary blood supply are carried out of the pelvis and ixed to the lateral abdominal wall at a site 3 to 4 cm above the level of the umbilicus. In one review, functional preservation was reported in 65 to 94 percent, depending on radiotherapy type (Gubbala, 2014). Also, such transposition requires transabdominal egg retrieval if later in vitro fertilization is planned (American Society for Reproductive Medicine, 20 13a).


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Obstentrics_Williams. Ovarian suppression with gonadotropin-releasing hormone agonists is not beneficial, according to a recent review (Elgindy, 2015). At this time, cryopreservation of ovarian tissue is considered investigational. These methods currently are limited to referral centers. In counseling cancer survivors, evidence suggests that exposure to most radiotherapy or chemotherapy agents in childhood or adulthood does not signiicantly increase the risk of congenital anomalies or genetic disease in their ofspring (Haggar, 2014; Signorello, 2012; Stensheim, 2013; Winther, 2012). In those treated as children with chemotherapy, studies also do not show a consistent link to adverse obstetrical outcomes (Melin, 2015; Reulen, 2009). Data are limited regarding those with cancer treated as an adult, and some studies have shown slightly higher rates of preterm birth and cesarean delivery (Haggar, 2014; Stensheim, 2013).


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Obstentrics_Williams. Notably, prior abdominopelvic radiation more convincingly afects neonatal outcomes. Adverse efects include elevated rates of abortion, low birthweight, stillbirth, and preterm birth (Signorello, 2006, 2010; Winther, 2008). Radiation may lower reproductive potential by creating reduced uterine volume, a thinned endometrium, and impaired uterine blood flow (Critchley, 1992; Larsen, 2004). Greater efects are seen with direct uterine radiation and with radiotherapy at younger ages (Teh,r2014). Importantly, many cancer survivors conceive by assisted reproductive technology, which by itself has associated obstetrical risks. his is discussed in Chapter 8 (p. 151).


Obstentrics_Williams

Obstentrics_Williams. Importantly, many cancer survivors conceive by assisted reproductive technology, which by itself has associated obstetrical risks. his is discussed in Chapter 8 (p. 151). Tumors infrequently metastasize to the placenta. As described in Chapter 6 (p. 116), the most common types are malignant melanomas, leukemias, lymphomas, and breast cancer (AlAdnani, 2007). Placentas from pregnancies in these and all other women with a malignancy should be sent for histological evaluation. Because tumor cells are usually confined within the intervillous spaces, fetal metastases are infrequent. Benign neoplasms are common and include leiomyomas, ovarian neoplasms, and endocervical polyps. Cancer in these organs may also complicate pregnancy, and of these, cervical neoplasia makes up the majority (Fig. 63-2).


Obstentrics_Williams

Obstentrics_Williams. These are overgrowths of endocervical stroma covered by epithelium. hey typically appear as single, red, elongated leshy masses of variable size that extend outward from the endocervical canal. Usually benign, they can bleed and can be a source of Pap test results describing aypical glandular cels of undetermined signiicance-AGUS. With removal and histological Ovary 23% Uterus, vulva, FIGURE 63-2 Frequency of reproductive-tract malignancies in 844 pregnant women. (Data from Haas, 1984; Lutz, 1977; Smith, 2003.) evaluation of these polyps, dysplasia is diagnosed in up to 0.5 percent, and there is malignant transformation in up to 0.1 percent (Esim Buyukbayrak, 2011; Long, 2013).


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Obstentrics_Williams. Few formal data guide management in pregnancy. Small asymptomatic lesions may be left alone to slough during delivery or puerperal remodeling. Removal and histological evaluation is reasonable if malignancy is suspected or if bleeding is trouble some. For those with a slender stalk, the polyp is grasped with ring forceps and twisted repeatedly about its base to strangulate feeding vessels. With repeated twisting, the base narrows and avulses. Monsel paste, which is ferric subsulfate, can be applied with pressure to the stalk stub for hemostasis. A thick-pedicle polyp may sometimes warrant surgical ligation and excision.


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Obstentrics_Williams. Pregnancy provides an opportune time to screen for cervical intraepithelial neoplasia (CIN), especially in women without regular access to health care. With Pap test screening, preg nancy status is noted on the requisition form because interpre changes. Some of these changes include presence of decidual cells and less often, Arias-Stella reaction. he latter gives an appearance of endocervical gland hyperplasia, which can make diferentiating this from truly atypical glandular cells diicult.


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Obstentrics_Williams. Screening guidelines also applicable in pregnant women were updated in 2012 by the American Society for Colposcopy and Cervical Pathology (ASCCP). hese include: (1) no screening until age 21, (2) cytology alone every 3 years in those aged 21 to 29 years, and (3) in those older than 30, human papillomavirus (HPV) and cytology co-testing every 5 years, or cytology alone every 3 years (Massad, 2013). High-risk conditions for cervical neoplasia include human immunodeficiency virus (HIV) infection, other immunocompromised states, and in utero diethylstilbestrol (DES) exposure. For women with HIV infection, initiation of cervical cancer screening with cytology alone begins within the first year after HIV diagnosis (American College of Obstetricians and Gynecologists, 20 16b).


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Obstentrics_Williams. Human Papillomaviru5. This virus infects cervical epithelia. In most instances, the infection clears, but in a smaller number, the virus may promote benign, premalignant, or cancerous neoplastic growth. he prevalence of HPV infection in pregnant women approximates 15 percent (Hong, 2013; Liu, 2014). here are more than 100 serotypes, and several are associated with high-grade intraepithelial lesions and invasive cancer. he most prominent of these are serotypes 16 and 18. Cervical cancer screening that combines both cytology and testing for high-risk HPV serotypes is termed co-testing and is suitable for women 30 years and older. Notably, as a new paradigm for screening, primary HPV testing alone can be considered an appropriate sole method for women older than 25 years (Huh, 2015). With this, identiication of serotypes 16 or 18 prompts colposcopic evaluation.


Obstentrics_Williams

Obstentrics_Williams. Serotypes HPV 6 and 11 are linked with benign maternal genital warts. Congenital HPV infection from vertical transmission-mother to fetus or newborn-beyond transient skin colonization is rare. Still, conjunctival, laryngeal, vulvar, or perianal warts present at birth in the neonate or that develop within 1 to 3 years of birth are most likely due to perinatal exposure to these maternal HPV serotypes. his is described further in Chapter 65 (p. 1245). Importantly, cesarean delivery does not lower the risk of neonatal laryngeal papillomatosis. has prompted development of three approved vaccines. These are not administered during pregnancy, are compatible with breastfeeding, and are discussed in Chapter 65 (p. 1245).


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Obstentrics_Williams. has prompted development of three approved vaccines. These are not administered during pregnancy, are compatible with breastfeeding, and are discussed in Chapter 65 (p. 1245). Abnormal Cytology and Histology. The incidence of abnor mal cervical cytology during pregnancy is at least as high as that reported for nonpregnant women. Abnormal cytological indings and their suggested management according to consen sus guidelines are summarized in Table 63-1. Many of these cytological abnormalities should prompt colposcopy, and the main goal during pregnancy is exclusion of invasive cancer.


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Obstentrics_Williams. Accordingly, lesions suspicious for high-grade disease or cancer should undergo biopsy. Unsatisfactory colposcopic evaluation is less common during pregnancy because the transformation zone is better exposed due to cervical eversion. With insui cient visualization of the zone, colposcopy is repeated in 6 to 8 weeks. During this time, the squamocolumnar junction usually will further evert to permit satisfactory examination.


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Obstentrics_Williams. Women with histologically confirmed CIN during pregnancy may be allowed to deliver vaginally, with further evaluation planned after delivery. For those with CIN 1, the recommended management is reevaluation postpartum. For those with CIN 2 or 3 in which invasive disease has been excluded, deferring reevaluation until at least 6 weeks postpartum is acceptable. Alternatively, repeat colposcopic and cytological evaluations are performed at intervals no more frequent than 12 weeks. Repeat biopsy is recommended only if appearance of the lesion worsens or if cytology suggests invasive cancer (Massad,r2013).


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Obstentrics_Williams. Regression of a CIN lesion is common during pregnancy or postpartum. In a study of 1079 pregnant women with cervical dysplasia in which biopsy correlated with colposcopic findings, 61 percent of lesions reverted to normal postpartum (Fader, 2010). In another study, Yost and colleagues (1999) reported postpartum lesion regression in 70 percent of women with CIN 2 or 3. And, although 7 percent of women had CIN 2 lesions that progressed to CIN 3, no lesion progressed to invasive carcinoma. In another study of 77 women with carcinoma in situ (CIS) diagnosed during pregnancy, a third had postpartum regression of their lesion, two thirds had persistent CIS, and only two women had microinvasive cancer on cone biopsy after delivery (Ackermann, 2006). Adenocarcinoma in situ (AIS) is managed similarly to CIN 3 (Dunton, 2008). hus, unless invasive cancer is identified, treatment of AIS is not recommended until 6 weeks postpartum.


Obstentrics_Williams

Obstentrics_Williams. Adenocarcinoma in situ (AIS) is managed similarly to CIN 3 (Dunton, 2008). hus, unless invasive cancer is identified, treatment of AIS is not recommended until 6 weeks postpartum. Cervical Conization. If invasive epithelial lesions are suspected, conization is indicated and may be done with loop electrosurgical excisional procedure (LEEP) or by cold-knife conization. However, the epithelium and underlying stroma within the endocervical canal cannot be extensively excised without the risk of membrane rupture. Logically, residual disease is common. Of 376 cone biopsies during pregnancy, Hacker and aWomen aged 30+ years. bEndocervical curettage and endometrial sampling are contraindicated in pregnancy. adenoCA = adenocarcinoma; AGC = atypical glandular cells; AIS = adenocarcinoma in situ; ASC-H = atypical squamous cells, cannot exclude high-grade squamous intraepithelialrlesion; ASC-US = atypical squamous cells of undetermined significance; HPV = human papillomavirus;


Obstentrics_Williams

Obstentrics_Williams. HSIL = high-grade squamous intraepithelialrlesion; LSIL = low7grade squamous intraepithelial lesion; NILM = negative for intraepithelialrlesion or malignancy; SCCA = squamous cell carcinoma. Adapted from American Society for Colposcopy and Cervical Pathology (ASCCP) 2012 Consensus Guidelines; Massad, 20lr3. Table summarized and used with permission from Dr. Claudia L. Werner. associates (1982) found residual neoplasia in 43 percent of subsequent specimens. In addition, nearly 10 percent of 180 pregnant women required transfusion after conization (Averette, 1970). hus, if possible, conization is avoided in pregnancy because of its higher risks for abortion, membrane rupture, hemorrhage, and preterm delivery.


Obstentrics_Williams

Obstentrics_Williams. Women with CIN treated bore pregnancy may also encounter pregnancy complications. First, cicatricial cervical stenosis is uncommon but may follow conization, LEEP, or laser surgery. Cervical stenosis almost always yields during labor. A so-called conglutinated cervix may undergo almost complete intrapartum efacement without dilation, and the presenting part is separated from the vagina by only a thin layer of cervical tissue. Spontaneous dilation usually promptly follows firm pressure with a ingertip, although instrumented dilation or cruciate incisions may be required. Second, preconceptional cold-knife conization is associated with cervical insuiciency and preterm birth. That said, the relationship between preterm birth and LEEP continues to be debated (Castanon, 2012; Conner, 2014; Stout, 2015; Werner, 2010). he size of tissue excised seems to be directly related to adverse outcomes (Weinmann, 2017).


Obstentrics_Williams

Obstentrics_Williams. he incidence of invasive cervical carcinoma has dramatically declined in the United States as a result of PAP testing (American College of Obstetricians and Gynecologists, 2016b). This cancer is found in approximately 1 in 8500 pregnancies (Bigelow, 2017; Pettersson, 2010). The diagnosis is conirmed with biopsies taken during colposcopy, with conization, or from a grossly abnormal lesion. Of the histological types, squamous cell carcinomas account for 75 percent of all cervical cancers, whereas adenocarcinomas compose the remainder. Cancers may appear as exophytic or endophytic growth; as a polypoid mass, papillary tissue, or barrel-shaped cervix; or as focal ulceration or necrosis. A watery, purulent, foul, or bloody discharge may also be present. Biopsy with Tischler forceps is warranted for suspicious lesions. Abnormal tumor vessels may cause heavier than expected biopsy-site bleeding, which is usually controlled by Monsel paste and pressure.


Obstentrics_Williams

Obstentrics_Williams. Cervical cancer is staged clinically, and 70 to 75 percent of cases that are diagnosed in pregnancy are stage I (Bigelow, 2017; Morice, 2012). Physiological pregnancy changes may impede accurate staging, and the extent of cancer is more likely to be underestimated in pregnant women. Specifically, induration of the broad ligament base, which characterizes tumor spread beyond the cervix, may be less prominent due to cervical, paracervical, and parametrial pregnancy-induced softening. Staging in pregnancy typically incorporates indings from pelvic examination and from renal sonography, chest radiography, cystoscopy, proctoscopy, and perhaps cone biopsy. Although MR imaging is not formally considered for clinical staging, it can be used without gadolinium contrast to ascertain involvement of the urinaty tract and lymph nodes (Fig. 63-3). FIGURE 63-3 Sagittal T2-weighted magnetic resonance image of a gravid uterus at 32 weeks' gestation with a large cervical carcinoma (arrows).


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Obstentrics_Williams. FIGURE 63-3 Sagittal T2-weighted magnetic resonance image of a gravid uterus at 32 weeks' gestation with a large cervical carcinoma (arrows). Management and Prognosis. Cervical cancer treatment in pregnant women is individualized, and factors include the clinical stage, fetal age, and individual desire to continue pregnancy. Stage IA1 is termed microinvasive disease and describes lesions with deepest invasion ;3 mm and widest lateral extension ;7 mm (FIGO Committee on Gynecologic Oncology, 2009). If diagnosed by cone biopsy, then treatment follows guidelines similar to those for intraepithelial disease. In general, continuation of pregnancy and vaginal delivery are considered safe, and definitive therapy is reserved until 6 weeks postpartum.


Obstentrics_Williams

Obstentrics_Williams. In contrast, invasive cancer demands relatively prompt therapy. During the first half of pregnancy, immediate treatment is advised by most, but this depends on the decision whether to continue pregnancy. During the latter half of pregnancy, most agree that pregnancy can safely be continued until fetal lung maturity is attained (Greer, 1989). In two studies with a total of 40 women past 20 weeks' gestation with either stage I or stage IIA carcinoma, delayed treatment was considered reasonable in women without bulky lesions (Takushi, 2002; van Vliet, 1998). Another option is to complete staging using laparoscopic lymphadenectomy and to delay treatment if metastases are excluded (louini, 2008; Favero, 2010). In a metaanalysis, neoadj uvant chemotherapy, that is, prior to surgery, with platinum derivatives was found to be promising for treatment in pregnancy (Zagouri, 2013a).


Obstentrics_Williams

Obstentrics_Williams. Although surgical therapy and radiation are equally efective, radical hysterectomy plus pelvic lymphadenectomy is the preferred treatment for invasive cervical cancer in most young women with stage I and early stage IIA lesions. Disadvantageously, radiotherapy for cervical cancer destroys ovarian and possibly sexual function, and frequently causes intestinal and urinary tract injury. In 49 women with pregnancy-associated stage IB cancer, a 30-percent severe complication rate accompanied radiotherapy compared with that of only 7 percent with radical surgery (Nisker, 1983). With surgery before 20 weeks' gestation, radical hysterectomy is usually performed with the fetus in situ. In later pregnancy, however, hysterotomy is oten performed first.


Obstentrics_Williams

Obstentrics_Williams. In later pregnancy, however, hysterotomy is oten performed first. Although less commonly selected during pregnancy, other cers. U ngGr and colleagues (2006) performed abdominal radical in five pregnant women. Yahata and associates (2008) treated four women at 16 to 23 weeks for stage IA1 adenocarcinoma with laser conization, and all delivered at term. Van Calsteren and coworkers (2008) reported similar success. For more advanced-stage cancer, radiotherapy is given. External beam radiation in early in pregnancy typically leads to spontaneous abortion. If miscarriage does not ensue, curettage is performed. During the second trimester, spontaneous abortion up to a fourth of cases. his is selected because labor induction or dilation and evacuation may pose serious hemorrhage risks. Pregnancy does not have a negative efect on the prognosis of cervical cancer, and survival outcomes are similar for preg nant and nonpregnant women (Amant, 2014; Mogos, 2013).


Obstentrics_Williams

Obstentrics_Williams. Pregnancy does not have a negative efect on the prognosis of cervical cancer, and survival outcomes are similar for preg nant and nonpregnant women (Amant, 2014; Mogos, 2013). In a case-control study of 44 women with pregnancy-associated cervical cancer, the overall 5-year survival rate approximated (van de' Vange, 1995). Delivery. Any adverse prognostic efects that vaginal delivery through a cancerous cervix might have are unknown. For this reason, the mode of delivery is controversial, especially for small, early-stage lesions. In some cases of bulky or friable tumors, significant hemorrhage from the cancer may complicate vaginal delivery. Also, recurrences have been reported in the episiotomy scar, which result from tumor cells apparently "seeding" the episiotomy (Goldman, 2003). Thus, most favor cesarean delivery.


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Obstentrics_Williams. Pregnancy ater Radical Trachelectomy. There is growing experience with pregnancy in women who have undergone fertility-sparing radical trachelectomy for stage IB 1 and IB2 cervical cancer before conception. During the typically vaginal procedure, the cervix is amputated at the level of the internal os, and a permanent-suture cerclage is placed around the isthmus for support in future pregnancies. The uterine isthmus is then reconstructed to the vagina. Because of the permanent cerclage, a classical cesarean incision is required for delivery. Shepherd and colleagues (2006) presented outcomes for 123 such women cared for at their institution. Of 63 women who attempted pregnancy, 19 had 28 live births. All underwent classical cesarean delivery, and one fourth delivered before 32 weeks. Similar findings were reported by Kim (2012) and Park (2014) and their coworkers. Also known as myomas and somewhat erroneously called ibrois, uterine leiomyomas are common benign smooth-muscle tumors.


Obstentrics_Williams

Obstentrics_Williams. Also known as myomas and somewhat erroneously called ibrois, uterine leiomyomas are common benign smooth-muscle tumors. heir incidence during pregnancy approximates 2 percent, and the cited range depends on the frequency of routine sonography and population characteristics (Qidwai, 2006; Stout, 2010). In one study of 4271 women, the irst-trimester leiomyoma prevalence was highest in black women-18 percent-and lowest in whites-8 percent (Laughlin, 2009).


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Obstentrics_Williams. Leiomyomas vary in location and may develop as submucous, subserosal, or intramural growths. Less often, these develop in the cervix or broad ligament. Some become parasitic and their blood supply is derived from adjacent structures such as the highly vascularized omentum. In one rare manifestation-leiomyomatosis peritonealis disseminata-numerous, small, benign subperitoneal smooth-muscle tumors appear similar to carcinomatosis. The tumors are likely caused by estrogen stimulation of multicentric subcoelomic mesenchymal cells to become smooth-muscle cells (Bulun, 2015). hese growths often regress after pregnancy. he stimulatory efects of pregnancy progesterone on myoma growth are unpredictable and can be impressive. hese tumors respond diferently in individual women and may grow, regress, or remain unchanged in size during pregnancy (Laughlin, 2009; Neiger, 2006).


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Obstentrics_Williams. Especially during pregnancy, myomas can be conused with other adnexal masses, and sonographic imaging is indispensable (Fig. 63-4). In women in whom sonographic indings are unclear, MR imaging performed ater the first trimester may be necessary. Once diagnosed, leiomyomas do not require surveillance with serial sonography unless associated complications are anticipated. Symptoms. Most leiomyomas are asymptomatic, but acute or chronic pain or pressure may develop. Large myomas more oten require admission for pain (Dogan, 2016). For chronic pain secondary to large tumor size, nonnarcotic analgesic drugs usually suice. More acutely, some myomas can outgrow their blood supply and hemorrhagic infarction follows, which is termed red


Obstentrics_Williams

Obstentrics_Williams. FIGURE 63-4 Sonogram of a pregnant uterus with a large uterine leiomyoma. The heterogeneous mass (arrows) lies beside the fetus (seen in cross section) and has the classic appearance of a leiomyoma in pregnancy. The placenta is located anteriorly, and the mass originates from the posterior lower uterine segment and occupies more than half of the total uterine volume. or carneous degeneration. Clinically, there is acute focal abdominal pain and tenderness, and sometimes a low-grade fever and leukocytosis. As such, tumor degeneration may be diicult to diferentiate from appendicitis, placental abruption, ureteral stone, or pyelonephritis. Sonographic imaging can be helpful, but close observation is requisite because an infarcted myoma is essentially a diagnosis of exclusion. In some women, preterm labor is stimulated by associated inlammation.


Obstentrics_Williams

Obstentrics_Williams. Treatment of a degenerated myoma is analgesic medications, and symptoms usually abate within a few days. In severe cases, close observation may be needed to exclude a septic cause. Although surgery is rarely necessary during pregnancy, myomectomy in highly selected cases has resulted in good outcomes. Of 23 reported cases, women were 14 to 20 weeks' gestation, and in almost half, surgery was performed because of pain (Celik, 2002; De Carolis, 2001). In some, an intramural leiomyoma was in contact with the implantation site. Except for one loss immediately following surgery at 19 weeks, most underwent cesarean delivery later, at term. Occasionlly, a pedunculated subserosal myoma will undergo torsion with subsequent painul necrosis. Laparoscopy or laparotomy can be used to ligate the stalk and resect the necrotic tumor. That said, we believe that surgery should be limited to tumors with a discrete pedicle that can be easily clamped and ligated.


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Obstentrics_Williams. Pregnancy Complications. Myomas are associated with several complications that include preterm labor, placental abruption, fetal malpresentation, obstructed labor, cesarean delivery, and postpartum hemorrhage. In a review of pregnancy outcomes in 2065 women with leiomyomas, Coronado and colleagues (2000) reported that placental abruption and breech presentation were each increased fourfold; irst-trimester bleeding and dysfunctional labor, twofold; and cesarean delivery, sixfold. Salvador and associates (2002) reported an eightfold higher second-trimester abortion risk in these women.


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Obstentrics_Williams. Factors most important in determining morbidity in pregnancy are leiomyoma number, size, and location (Ciavattini, 2015; Jenabi, 2018; Lam, 2014). If the placenta is adjacent to or implanted over a leiomyoma, rates of abortion, preterm labor, placental abruption, and postpartum hemorrhage are all increased. Retroplacental myomas are also associated with fetal-growth restriction (Knight, 2016) . Tumors in the cervix or lower uterine segment may obstruct labor, as did the one shown in Figure 63-5. Despite these complications, Qidwai and associates (2006) reported a 70-percent vaginal delivery rate in women in whom myomas measured : 10 cm. hese data argue against empirical cesarean delivery for leiomyomas, and we allow a trial of labor unless myomas clearly obstruct the birth canal. If cesarean delivery is indicated, uterine malrotation should be excluded prior to hysterotomy. Myomas are generally let alone unless they cause recalcitrant bleeding. n important caveat is that cesarean


Obstentrics_Williams

Obstentrics_Williams. delivery is indicated, uterine malrotation should be excluded prior to hysterotomy. Myomas are generally let alone unless they cause recalcitrant bleeding. n important caveat is that cesarean hysterectomy may be technically diicult because of lateral ureteral displacement by the masses.


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Obstentrics_Williams. Bleeding due to myomas may develop during pregnancy from any of several factors. Especially common is bleeding with miscarriage, preterm labor, placenta previa, and placental abruption. Much less often, bleeding may result from a submucous myoma that has prolapsed from the uterus and into the cervix or vagina. In this unusual circumstance, although heavy or persistent bleeding may require earlier intervention, the stalk, if accessible, can be ligated vaginally near term to avoid tumor avulsion during delivery. FIGURE 63-5 Cesarean delivery performed because of a large leiomyoma in the lower uterine segment. A classical vertical uterine incision, seen to the left of the myoma, was required for delivery of the fetus. Fortunately, myomas rarely become infected (Genta, 2001).


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Obstentrics_Williams. Fortunately, myomas rarely become infected (Genta, 2001). When infection develops, it usually is postpartum, especially if the tumor is located immediately adjacent to the implantation site (Lin, 2002). hey also may become infected with an associated septic abortion and myoma perforation by a sound, dilator, or curette. Fertility Considerations. Despite the relatively high prevalence of myomas in young women, it is not clear whether they diminish fertility, other than by possibly causing miscarriage. In a review of 11 studies, Pritts (2001) concluded that submucous myomas did signiicantly afect fertility. He also found that hysteroscopic myomectomy improved infertility and early miscarriage rates in these women. If truly implicated in infertility, myomas in other locations may require laparoscopy or laparotomy for excision.


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Obstentrics_Williams. Some of these methods of treatment for infertility may afect subsequent pregnancies. For example, after myomectomy, the gravid uterus can rupture either before or during labor (American College of Obstetricians and Gynecologists, 20 16a). Management is individualized, and review of the prior operative report is prudent. If resection resulted in a defect into or immediately adjacent to the endometrial cavity, then cesarean delivery is usually done before labor begins. Although less efective than surgery, uterine artery embolization of myomas has also been used to treat infertility or symptoms (Mara, 2008). Women so treated have higher rates of miscarriage, cesarean delivery, and postpartum hemorrhage (Homer, 2010). he Society of Interventional Radiology considers myoma embolization relatively contraindicated in women who plan future pregnancies (Stokes, 2010).


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Obstentrics_Williams. Finally, outside the United States, ulipristal-a selective progesterone-receptor modulator-can be used for myoma regression. Successful subsequent pregnancies without tumor regrowth have been reported (Luycx, 2014). Occasionally, endometriosis can develop after delivery from otomy scars (Bumpers, 2002). Here, they form a palpable mass and can cause cyclic localized pain. Endometriomas within an ovary are discussed in the next section. Adenomyosis is traditionally found in late reproductive life and beyond. Its acquisition may be at least partially related to disruption of the endometrial-myometrial border during sharp curettage for abortion (Curtis, 2002). In a case-control study, associated rates of second-trimester abortion, preeclampsia, fetal malposition, and preterm delivery.


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Obstentrics_Williams. Endometrial carcinoma is an estrogen-dependent neoplasia also usually found in women older than 40 years. hus, it is seen only rarely with pregnancy. Of 27 cases that were identi fied during pregnancy or within the irst 4 months postpartum, nuna, 2009). These are usually early-stage, well-diferentiated adenocarcinomas for which treatment consists primarily of tomy. Much less commonly, to preserve future fertility, curet tage with or without postprocedural progestational therapy has been used for the rare patient with cancer identified in a miscar riage curettage specimen (Schammel, 1998).


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Obstentrics_Williams. Many more studies describe a conservative approach for well-selected nonpregnant women diagnosed with endometrial cancer who wish to preserve fertility. One study followed 13 women treated with progestins for early-stage, well-diferentiated adenocarcinoma who then later conceived after apparent remission (Godieb, 2003). Nine had liveborn neonates, and four of six women with a recurrence responded to another course of therapy. Similar outcomes were described in 12 women by Niwa (2005) and in 21 women by Signorelli (2009), each with their coworkers. Despite these acceptable pregnancy rates, recurrences and death have been reported, and conservative management is not considered standard (Erkanli, 2010).


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Obstentrics_Williams. Ovarian masses found during pregnancy are relatively common. Among studies, incidences vary depending on the frequency of prenatal sonography, the ovarian size threshold used to define a clinically signiicant "mass," and whether the study site is tertiary or primary care. Thus, the incidence of ovarian masses not surprisingly ranges from 1 in 100 to 2000 pregnancies (Whitecar, 1999; Zan etta, 2003). Of ovarian malignancies, the absolute incidence in the California Cancer Registry was 1 in 19,000 pregnancies (Smith, 2003). The most frequent types of ovarian masses are corpus luteum cysts, endometriomas, benign cystadenomas, and mature cystic teratomas. Because pregnant women are usually young, malignant tumors and those of low malignant potential are proportionately uncommon. Our experiences from Parkland Hospital are similar to those of Leiserowitz and associates (2006), who


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Obstentrics_Williams. FIGURE 63-6 Sonographic characteristics of common adnexal masses in pregnancy. A. A simple anechoic cyst with smooth walls is characteristic of a physiological corpus luteum cyst or benign cystadenoma. B. Cystic structure with difuse internal low-level echoes sug gestive of an endometrioma or hemorrhagic corpus luteum. C. Mature cystic teratoma appears as an adnexal cyst (marked by calipers) with accentuated lines and dots that represent hair in both longitudinal and transverse planes. At the central inferior aspect of this cyst, a mural nodule-Rokitansky protuberance-is seen. These typically rounded protuberances range in size from 1 to 4 cm, they are predominantly hyperechoic, and they create an acute angle with the cyst wall. Although not seen here, fat-fluid levels are often identified with cystic teratomas. (Used with permission from Dr. Elysia Moschos.) found that 1 percent of9375 ovarian masses were frankly malignant and that another 1 percent were of low malignant potential.


Obstentrics_Williams

Obstentrics_Williams. with cystic teratomas. (Used with permission from Dr. Elysia Moschos.) found that 1 percent of9375 ovarian masses were frankly malignant and that another 1 percent were of low malignant potential. In surgically excised masses, rates of malignancy are higher, vary from 4 to 13 percent, and probably reRect a greater preoperative concern for cancer (Hofman, 2007; Sherard, 2003).


Obstentrics_Williams

Obstentrics_Williams. Most ovarian masses are asymptomatic in pregnant women. Some cause pressure or chronic pain, and acute abdominal pain may be due to torsion, rupture, or hemorrhage. Seldom is blood loss signiicant enough to cause hypovolemia. Many ovarian masses are detected during routine prenatal sonography or during imaging done for other indications, including evaluation of symptoms. The typical sonographic appearance of these masses is shown in Figure 63-6. In some instances, MR imaging can be used to evaluate complicated anatomy.


Obstentrics_Williams

Obstentrics_Williams. Cancer antigen 125 (CA125) serves as a tumor marker, and levels are frequently elevated with ovarian malignancy. Importantly, concentrations of CA125 in early pregnancy and early puerperium are normally elevated, possibly from the decidua (slam , 2000; Spitzer, 1998). As shown in the Appendix (p. 1257), from the second trimester until term, levels are not normally higher than those in the nonpregnant woman (Szecsi, 2014). With severe preeclampsia, however, levels are abnormally elevated (Karaman, 2014). Other tumor markers that are not useul for diagnosis or posttreatment surveillance in pregnancy include human chorionic gonadotropin (hCG) , alpha-fetoprotein, inhibins A and B, and the multimarker OVAl test (Liu, 2011).


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Obstentrics_Williams. The two most common are torsion and hemorrhage. Torsion usually causes acute constant or episodic lower abdominal pain that frequently is accompanied by nausea and vomiting. Sonography often aids the diagnosis. With color Doppler, presence of an ovarian mass with absent Row strongly correlates with torsion. However, minimal or early twisting may compromise only venous Row, thus leaving the arterial supply intact. If torsion is suspected, laparoscopy or laparotomy is warranted. Contrary to prior teaching, adnexectomy is generally unnecessary to avoid clot release, thus, most recommend attempts at untwlstmg (McGovern, 1999; Zweizig, 1993). With a salvageable ovary, within minutes, congestion is relieved, and ovarian volume and cyanosis diminish. If cyanosis persists, however, then removal of the infarcted adnexum is typically indicated.


Obstentrics_Williams

Obstentrics_Williams. If the adnexum is healthy, there are options. First, neoplasms are resected. However, ovarian cystectomy in an ischemic, edematous ovary may be technically diicult, and adnexectomy may be necessary. Second, unilateral or bilateral oophoropexy has been described to minimize the risk of repeated torsion (Djavadian, 2004; Germain, 1996). Techniques described include shortening of the utero ovarian ligament or fixing the utero ovarian ligament to the posterior uterus, the lateral pelvic wall, or the round ligament (Fuchs, 2010; Weitzman, 2008).


Obstentrics_Williams

Obstentrics_Williams. he most common cause of ovarian hemorrhage follows rupture of a corpus luteum cyst. If the diagnosis is certain and symptoms abate, then observation and surveillance is usually suicient. Concern for ongoing bleeding will typically prompt surgical evaluation. If the corpus luteum is removed before 10 weeks' gestation, progestational support is recommended to maintain the pregnancy. Suitable regimens include: (1) micronized progesterone (Prometrium) 200 or 300 mg orally once daily; (2) 8-percent progesterone vaginal gel (Crinone), one premeasured applicator vaginally daily plus micronized progesterone 100 or 200 mg orally once daily; or (3) intramuscular 17 -hydroxyprogesterone caproate, 150 mg. The first two regimens are given until 10 completed weeks. For the last, if given between 8 and 10 weeks' gestation, only one injection is required immediately after surgery. If the corpus luteum is excised between 6 and 8 weeks' gestation, then two additional doses should be given 1 and 2 weeks


Obstentrics_Williams

Obstentrics_Williams. weeks' gestation, only one injection is required immediately after surgery. If the corpus luteum is excised between 6 and 8 weeks' gestation, then two additional doses should be given 1 and 2 weeks after the irst.


Obstentrics_Williams

Obstentrics_Williams. Because most of these are incidental findings, management considerations include whether resection is necessary and its timing. A cystic benign-appearing mass that is <5 cm often requires no additional antepartum surveillance. Early in pregnancy, this is likely a corpus luteum cyst, which typically resolves by the early second trimester. For cysts ::10 cm, because of the substan tial risk of malignancy, torsion, or labor obstruction, surgical removal is reasonable. Tumors between 5 and 10 cm should be carefully evaluated by sonography along with color Doppler and possibly MR imaging. If they have a simple cystic appear ance, these cysts can be managed expectantly with sonographic surveillance (Schmeler, 2005; Zan etta, 2003). Resection is done if cysts grow, begin to display malignant qualities, or become symptomatic. hose with classic indings of endometrioma or cesarean for obstetrical indications.


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Obstentrics_Williams. On the other hand, if sonographic characteristics suggest cancer-thick septa, nodules, papillary excrescences, or solid components-immediate resection is indicated (Caspi, 2000). In one review of 563 masses, approximately half were simple, and the other half complex (Webb, 2015). Among simple masses, 1 percent were malignant, and of complex masses, 9 percent were cancerous. Approximately 1 in 1000 pregnant women undergoes surgical exploration for an adnexal mass (Boulay, 1998). In general, we plan resection at 14 to 20 weeks' gestation because most masses that will regress will have done so by this time. As outlined in Chapter 46 (p. 901), laparoscopic removal is ideal (Naqvi, 2015; Sisodia, 2015). Importantly, in any instance in which cancer is strongly suspected, the American College of Obstetricians and Gynecologists (2017b) recommends consultation with a gynecologic oncologist.


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Obstentrics_Williams. Pregnancy Luteoma. One group of ovarian masses results directly from the stimulating efects of various pregnancy hormones on ovarian stroma. These include pregnancy luteoma, hyperreactio luteinalis, and ovarian hyperstimulation syndrome. Of these, pregnancy luteoma is a rare, benign ovarian neoplasm that arises from luteinized stromal cells and classically causes elevated testosterone levels (Hakim, 2016; Irving, 2011). Up to 25 percent of afected women will be virilized, and of these afected women, nearly half of their female fetuses will have some degree of virilization. However, most mothers and their fetuses are unafected because the placenta rapidly converts testosterone to estrogen (KanovG, 2011).


Obstentrics_Williams

Obstentrics_Williams. In typical cases, an adnexal mass along with maternal virilization will prompt sonography and measurement of testosterone and CA125 levels. Luteomas range in size from microscopic to >20 cm. hey appear as solid tumors, may be multiple or bilateral, and may be complex because of internal hemorrhage (Choi, 2000). Concerns for malignancy may be further investigated with MR imaging (Kao, 2005; Tannus, 2009). Total testosterone levels are increased, but notably, levels in normal pregnancy can be substantially elevated (Appendix, p. 1259). Diferential diagnoses include granulosa cell tumors, thecomas, Sertoli-Leydig cell tumors, Leydig cell tumors, stromal hyperthecosis, and hyperreactio luteinalis.


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Obstentrics_Williams. Generally, luteomas do not require surgical intervention unless there is torsion, rupture, or hemorrhage (Masarie, 2010). hese tumors spontaneously regress during the irst few months postpartum, and androgen levels drop precipitously during the irst 2 weeks following delivery (Wang, 2005). Lactation may be delayed a week or so by hyperandrogenemia (Dahl, 2008). Recurrence in subsequent pregnancies is rare. Hyperreactio Luteinalis. In this condition, one or both ovaries develop multiple, large theca-lutein cysts, typically after the first trimester. Cysts are caused by luteinization of the follicular theca interna layer, and most are in response to stimulation by excep tionally high hCG levels (Russell, 2009). For this reason, they are more common with gestational trophoblastic disease, twins, fetal hydrops, and other conditions with increased placental mass. Maternal virilization may develop, but fetal virilization has not been reported (KanovG, 2011; Malinowski, 2015).


Obstentrics_Williams

Obstentrics_Williams. s reported by Baxi and coworkers (2014), these ovarian tumors appear sonographically to have a "spoke wheel" pattern (Fig. 20-3, p. 391). If the diagnosis is confident, and unless com plicated by torsion or hemorrhage, surgical intervention is not required. hese masses resolve ater delivery. Few data allow pre diction of risk in a subsequent pregnancy, but in one case report, a woman had hyperreactio with three pregnancies (Bishop, 2016).


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Obstentrics_Williams. Ovarian Hyperstimulation Syndrome. This is typified by multiple ovarian follicular cysts accompanied by increased capillary permeability. It most often is a complication of ovulationinduction therapy for infertility, although it rarely may develop in an otherwise normal pregnancy. It has also been reported with a partial molar pregnancy (Suzuki, 2014). Its etiopathogenesis is thought to involve hCG stimulation of vascular endothelial growth factor (VEGF) expression in granulosa-lutein cells (Soares, 2008). This causes greater that can lead to ascites, pleural or pericardial efusion, hypovolemia with acute kidney injury, and hypercoagulability. Serious complications are renal dysfunction, adult respiratory distress syndrome, ovarian rupture with hemorrhage, and VTE. Unlike hyperreactio lutealis, virilization is absent (Suzuki, 2004).


Obstentrics_Williams

Obstentrics_Williams. Detailed guidelines for management are outlined by the American Society for Reproductive Medicine (2016). Treatment is primarily supportive with attention to maintaining vascular volume and thromboprophylaxis. In severe cases, paracentesis can be helpful. Malignancies of the ovary are the leading cause of death from genital-tract cancers in all women (American Cancer Society, 2017). Still, it is uncommon in young women, and the incidence of ovarian malignancy ranges from 1 in 20,000 to 1 in 50,000 births (Eibye, 2013; Palmer, 2009). Fortunately, 75 percent of these found in pregnancy are early-stage cancers that carry a 5-year survival rate between 70 and 90 percent (Brewer, 2011). The types of malignancy are also markedly diferent in pregnant women compared with those in older women. In gravidas, these are, in decreasing order of frequency, germ cell and sex cord-stromal tumors, low-malignant-potential tumors, and epithelial tumors (Morice, 2012).


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Obstentrics_Williams. Pregnancy apparently does not alter the prognosis of most ovarian malignancies. Management is similar to that for nonpregnant women, with the usual proviso that it may be modiied depending on gestational age. Thus, if frozen section histopathological analysis veriies malignancy, surgical staging is done with careful inspection of all accessible peritoneal and visceral surfaces (Giuntoli, 2006). Peritoneal washings are taken for cytology, biopsies are obtained from the diaphragmatic surface and peritoneum, omentectomy is completed, and pelvic and infrarenal paraaortic lymph nodes are sampled, if accessible.


Obstentrics_Williams

Obstentrics_Williams. If there is advanced disease, bilateral adnexectomy and omentectomy will decrease most tumor burden. In early pregnancy, hysterectomy and aggressive surgical debulking procedures may be elected. In other cases, minimal debulking as described in the previous paragraph is done and the operation terminated. In some cases of aggressive or large-volume disease, chemotherapy can be given during pregnancy while awaiting pulmonary maturation. Monitoring maternal CA125 serum levels during chemotherapy is not accurate in pregnancy (Aslam, 2000; Morice, 2012).


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Obstentrics_Williams. Paratubal and paroovarian cysts are either distended remnants of the paramesonephric ducts or are mesothelil inclusion cysts. Although most measure 53 cm, they occasionally attain worrisome dimensions. Their reported incidence is inluenced by size, but one autopsy series in nonpregnant women cited this to be 5 percent (Dorum, 2005). The most common parmesonephric cyst is the hydatid of Morgagni, which is pedunculated and typically dangles from one of the imbria. hese cysts infrequently cause complications and are most oten identiied at the time of cesarean delivery or puerperal sterilization. In these instances, they can simply be excised or drained by creating a large window in the cyst wll. Neoplastic paraovarian cysts are rare, sonographically and histologically resemble tumors of ovarian origin, and rarely are of borderline potential or frankly malignant (Korbin, 1998).


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Obstentrics_Williams. Preinvasive disease in young women-vulvar intraepithelial neoplasia (YIN) and vaginal intraepithelial neoplasia (VAIN)are seen more often than invasive disease and are commonly associated with HPV infection. As with cervical neoplasia, these premalignant conditions are treated after delivery. Cancer of the vulva or vagina is generally a malignancy of older women, and thus, these are rarely associated with pregnancy. Even so, any suspicious lesions should be biopsied. Treatment is individualized according to the clinical stage and depth of invasion. In a review of 23 cases, investigators concluded that radical surgery for stage I disease was feasible during pregnancy-including in the last trimester (Heller, 2000).


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Obstentrics_Williams. We and others question the necessity of resection in late pregnany because deinitive therapy can oten be delayed due to these cancers' typically slow progression (Anderson, 2001). It appears that vaginal delivery is not contraindicated if vulvar and inguinal incisions are well healed. Vulvar sarcoma, vulvar melanoma, and vaginal malignancies are rare in pregnancy and are the subjects of case reports (lexander, 2004; Kuller, 1990; Matsuo, 2009).


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Obstentrics_Williams. Breast cancer rates rise most acutely between ages 40 and 80 years. However, because of its overall high frequency, breast cancer is relatively common even in younger women and is the most frequent cancer found in gravidas. From the Nationwide Inpatient Sample of 11.8 million births, the incidence approximated 1 in 15,000 (Maor, 2017). And, as more women choose to delay childbearing, the frequency of associated breast cancer is certain to grow. Postponed childbearing was considered partially responsible for the increase in pregnancy-associated breast cancer in Sweden and Denmark (Andersson, 2015; Eibye, 2013).


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Obstentrics_Williams. Some studies suggest that women with a family history of breast cancer-especially those with BRCAl and BRC2 breast cancer gene mutations-are more likely to develop breast malignancy during pregnancy (Wohlfahrt, 2002). However, it may be that it is parity that modiies this risk. Namely, parous women older than 40 years with these mutations have a signiicantly lower cancer risk than nulliparas with these mutated genes (Andrieu, 2006; Antoniou, 2006). Women with BRAl and BRC2 gene mutations who undergo induced abortion or those who breastfeed do not have an increased breast cancer risk (Friedman, 2006). Moreover, Jernstrom and associates (2004) found that breastfeeding conveyed a protective efect against this cancer in those with BRCAl gene mutation, but not in those with BRCA2 mutations. Of other congenital factors, it is controversial whether DES exposure raises breast cancer risks (Hoover, 2011; Titus-Ernstof, 2006).


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Obstentrics_Williams. More than 90 percent of gravidas with breast cancer have a palpable mass, and greater than 80 percent of cases are selfreported (Brewer, 2011). In pregnancy, clinical assessment, diagnostic procedures, and treatment of women with breast tumors are often slightly delayed (Berry, 1999). his can be partially attributed to pregnancy-induced breast tissue that obscures masses.


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Obstentrics_Williams. The evaluation of pregnant women with a breast mass does not difer from that for nonpregnant women (Loibl, 2015). hus, any suspicious breast mass should be pursued to diagnosis. Pragmatically, a palpable discrete mass can be biopsied or excised. If imaging is desirable to distinguish between a solid mass and a cystic lesion, sonography has high sensitivity and specificity (Navrozoglou, 2008). Mammography is appropriate if indicated, and the fetal radiation risk is negligible-0.04 mGywith appropriate shielding (rishna, 2013). But, because breast tissue is denser in pregnancy, mammography has a false-negative rate of 35 to 40 percent (Woo, 2003). If the decision to biopsy is uncertain, then MR imaging may be used. With such techniques, masses can usually be described as either solid or cystic.