Obstentrics_Williams

Obstentrics_Williams. Enders M, Weidner A, Zoellner I, et al: Fetal morbidity and mortality after acute human parvovirus B 19 infection in pregnancy: prospective evaluation of 1018 cases. Prenat Diagn 24:513, 2004 Fairlie T, Zell ER, Schrag S: Efectiveness of intrapartum antibiotic prophylaxis for prevention of early-onset Group B streptococcal disease. Obstet Gynecol 121(3):570,t2013 Fell DB, Savitz DA, Kramer MS, et al: Maternal influenza and birth outcomes: systematic review of comparative studies. BJOG 124(1):48,t201 Fiebelkorn AP, Redd SB, Gallagher K, et al: Measles in the United States during the postelimination era. J Infect Dis 202(10): 1520, 2010 Filisetti 0, Year H, Villard 0, et al: Contribution of neonatal amniotic fluid testing to diagnosis of congenital toxoplasmosis. J Clin Microbiol 53(5):1719,t2015


Obstentrics_Williams

Obstentrics_Williams. Filisetti 0, Year H, Villard 0, et al: Contribution of neonatal amniotic fluid testing to diagnosis of congenital toxoplasmosis. J Clin Microbiol 53(5):1719,t2015 Forcade NA, Wiederhold NP, Ryan L, et al: Antibacterials as adjuncts to incision and drainage for adults with purulent methicillin-resistant Staphylococcus aureus (MRSA) skin infections. Drugs 72:339, 2012 Forsnes EV, Eggleston MK, WaxJR: Diferential transmission of adenovirus in a twin pregnancy. Obstet Gynecol , 1998 Fowler KB, Stagno S, Pass RF, et al: The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med 326:663, 1992 Fowler KB, Stagno S, Pass F: Maternal immunity and prevention of congenital cytomegalovirus infection. J1A 289: 1 008, 2003 Fowler SL: A light in the darkness: predicting outcomes for congenital cytomegalovirus infections. J Pediatr 137:4, 2000


Obstentrics_Williams

Obstentrics_Williams. Fowler SL: A light in the darkness: predicting outcomes for congenital cytomegalovirus infections. J Pediatr 137:4, 2000 Fragiadakis GK, Baca QJ, Gherardini PF, et al: Mapping the fetomaternal peripheral immune system at term pregnancy. J Immunol 197(11):4482, 2016 Freedman DO, Chen LH, Kozarsky PE: Medical considerations before international travel. N Engl J Med 375(3):247, 2016 Freeman K, Oakley L, Pollak A, et al: Association between congenital toxoplasmosis and preterm birth, low birthweight and small for gestational age birth. BJOG 112:31,2005 Gimovsky AC, Macri CJ: Leprosy in pregnant woman, United States. Emerg Infect Dis 19:10,t2013 Gotwitz J, Kruszon-Moran 0, McAllister SK: Changes in the prevalence of nasal colonization with Staphylococcus aureus in the United States, 20012004. J Infect Dis 197:1226,t2008 Grant GB, Reef SE, Dabbagh A, et al: Global progress roward rubella and congenital rubella syndrome control and elimination-2004-2014. MMWR 64(37):1052,t2015


Obstentrics_Williams

Obstentrics_Williams. Grant GB, Reef SE, Dabbagh A, et al: Global progress roward rubella and congenital rubella syndrome control and elimination-2004-2014. MMWR 64(37):1052,t2015 Granwehr BP, Lillibridge M, Higgs S, et al: West Nile virus: where are we now? Lancet Infect Dis 4:547,t2004 Guerra B, Lazzarotto T, Quarta S, et al: Prenatal diagnosis of symptomatic congenital cytomegalovirus infection. Am J Obstet GynecoIt183:476, 2000 Hamilton SM, Stevens DL, Bryant AE: Pregnancy-related Group A streptococcal infections: temporal relationship between bacterial acquisition, infection onset, clinical findings, and outcome. Clin Infect Dis 0,t2013 Harjulehto T, Aro T, Hovi T, et al: Congenital malformations and oral poliovirus vaccination during pregnancy. Lancet 1:771, 1989 Hayes EB, Piesman J: How can we prevent Lyme disease? N Engl J Med 348: 2424,t2003


Obstentrics_Williams

Obstentrics_Williams. Hayes EB, Piesman J: How can we prevent Lyme disease? N Engl J Med 348: 2424,t2003 Hedriana HL, Mitchell JL, Williams SB: Salmonella ryphi chorioamnionitis in a human immunodeiciency virus-infected pregnant woman. J Reprod Med 40:157,t1995 Helali NE, Giovangrandi Y, Guyot K, et al: Cost and efectiveness of intrapartum Group B streptococcus polymerase chain reaction screening for term deliveries. Obstet Gynecol 119(4):822,t2012 Hendricks A, Wright ME, Shadomy SV, et al: Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 20(2):1,t2014 Hills SL, Russell K, Hennessey M, et al: Transmission of Zika virus through sexual contact with travelers to areas of ongoing transmission-Continental United States. MMWR 65(8):215,t2016 Holry JE, Bravata OM, Liu H, et al: Systemic review: a century of inhalational anthrax cases from 1900 to 2005. Ann Intern Med 144:270,t2006


Obstentrics_Williams

Obstentrics_Williams. Holry JE, Bravata OM, Liu H, et al: Systemic review: a century of inhalational anthrax cases from 1900 to 2005. Ann Intern Med 144:270,t2006 Honein A, Dawson AL, Petersen EE, et al: Birth defects among fetuses and infants of US women with evidence of possible Zika virus infection during pregnancy. JAMA 317(1):59,t2017 Hotop A, Hlobil H, Gross U: Eicacy of rapid treatment initiation following primary Toxoplasma gondii infection during pregnancy. Clin Infect Dis 54(1t1):1545,t2012 Howard MJ, Doyle TJ, Koster FT, et al: Hantavirus pulmonary syndrome in pregnancy. Clin Infect Dis 29: 1538, 1999 Hutton J, Rowan P, Greisinger A, et al: Rubella monitoring in pregnancy as a means for evaluating a possible reemergence of rubella. Am J Obstet GynecoI211(5):534.e1,t2014


Obstentrics_Williams

Obstentrics_Williams. Hutton J, Rowan P, Greisinger A, et al: Rubella monitoring in pregnancy as a means for evaluating a possible reemergence of rubella. Am J Obstet GynecoI211(5):534.e1,t2014 Hyde TB, Schmid OS, Cannon MJ: Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV. Rev Med Virol 20:311, 2010 Inglesby TV, O'Toole T, Henderson DA, et al: Anthrax as a biological weapon, 2002. JAMA 287:2236, 2002 Irving WL, James OK, Stephenson T, et al: Influenza virus infection in the second and third trimesters of pregnancy: a clinical and seroepidemiological study. BJOG 107: 1282, 2000 Jamieson OJ, Uyeki TM, Callaghan WM, et al: Xfhat obstetrician-gynecologists should know about Ebola: a perspective from the Centers for Disease Control and Prevention. Obstet GynecoIt124(5):1005, 2014


Obstentrics_Williams

Obstentrics_Williams. Jespersen C, Helmuth IG, Krause TG: Varicella-zoster immunoglobulin treatment in pregnant women in Denmark from 2005 to 2015: descriptive epidemiology and follow-up. Epidemiol Infect August 18, 2016 [Epub ahead of print] Jimenez-Truque N, Tedeschi S, Saye EJ, et al: Relationship between maternal and neonatal Staphylococcus aureus colonization. Pediatrics 129:e1252, 2012 Joguet G, Mansuy JM, Matusali G, et al: Efect of acute Zika virus infection on sperm and virus clearance in body fluids: a prospective observational study. Lancet Infect Disease August 21, 2017 [Epub ahead of print] Jones JL, Parise ME, Fiore AE: Neglected parasitic infecrions in the United States: toxoplasmosis. Am J Trop Med Hyg 90(5):794,t2014


Obstentrics_Williams

Obstentrics_Williams. Jones JL, Parise ME, Fiore AE: Neglected parasitic infecrions in the United States: toxoplasmosis. Am J Trop Med Hyg 90(5):794,t2014 Julander JG, Winger QA, Rickords LF, et al: West Nile virus infection of the placenta. Virology 347: 175,t2006 Kakuru A, Jagannathan P, Muhindo MK, et al: Dihydroartemisinin-Piperaquine for the prevention of malaria in pregnancy. N Engl J Med 374(10): 928,t2016 Kanengisser-Pines B, Hazan Y, Pines G, et al: High cytomegalovirus IgG avidity is a reliable indicator of past infection in patients with positive IgM detected during the first trimester of pregnancy. J Perinat Med 37: 15, 2009 Kashif AH, Adam GK, Mohammed AA, et al: Reliabiliry of rapid diagnostic test for diagnosing peripheral and placental malaria in an area of unstable malaria transmission in Eastern Sudan. Diagn Pathol 8:59,t2013


Obstentrics_Williams

Obstentrics_Williams. Kharbanda EO, Vasquez-Benitez G, Romitti PA, et al: First trimester influenza vaccination and risks for major structural birth defects in ofspring. J Pediatr 187:234,t2017 Kim , Kasper LH: Toxoplasma infections. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Intenal Medicine, 19th ed. New York, McGraw-Hili, 2015 Kimberlin OW, Sanchez PJ, Ahmed A, et al: Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 3 2(10):933, 2015 Kobayashi M, Schrag SJ, Alderson MR, et al: WHO consultation on group B streptococcus vaccine development: report from a meeting held on 2 -28 April 2016. Vaccine December 22,t2016 [Epub head of print] Koro'ikova EL, Lozovskaia LS, T adtaeva U, et al: The role of prenatal coxsackie virus infection in the etiology of congenital heart defects in children. Kardiologiia 29:68, 1989 Kourtis AP, Read JS, Jamieson OJ: Pregnancy and infection. N Engl J Med 370(23):2211,t2014


Obstentrics_Williams

Obstentrics_Williams. Kourtis AP, Read JS, Jamieson OJ: Pregnancy and infection. N Engl J Med 370(23):2211,t2014 Krow-Lucal E, Lindsey NP, Lehman J, et al: West Nile virus and other nationally notifiable diseases-United States. MMWR 66(2):51,t2017 Kuhn JH: Ebolavirus and marburgvirus infections. In Kasper OL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Internal Medicine, 19th ed. New York, McGraw-Hili, 2015 Kurppa K, Holmberg PC, Kuosma E, et al: Anencephaly and maternal common cold. Teratology 44: 51, 1991 Kutty PK, Kyaw MH, Dayan GH, et al: Guidance for isolation precautions for mumps in the US: a review of the scientiic basis for policy change. Clin Infect Disease 50(112):169, 2010 Kwatra G, Cunnington MC, Merrall E, et al: Prevalence of maternal colonization with group B streptococcus: a systematic review and meta-analysis. Lancet Infect Dis 16(9):1076,t2016


Obstentrics_Williams

Obstentrics_Williams. Kwatra G, Cunnington MC, Merrall E, et al: Prevalence of maternal colonization with group B streptococcus: a systematic review and meta-analysis. Lancet Infect Dis 16(9):1076,t2016 Kylat RI, Bartholomew A, Cramer N, et al: Neonatal listeriosis: uncommon or misdiagnosed? J Neonatal Perinatal Med 9(3):313, 2016 Laibl VR, Sheield JS, Roberts S, et al: Clinical presentation of communiryacquired methicillin-resistant Staphylococcus aureus in pregnancy. Obstet Gynecol 106:461, 2005 Lam CM, Wong SF, Leung TN, et al: A case-controlled study comparing clinical course and outcomes of pregnant and non-pregnant women with severe acute respiratory syndrome. BJOG 11t1:771, 2004 Lambert N, Strebel P, Orenstein W: Rubella. Lancet 385:2297,t2015 Lamont RF, Sobel JD, Carrington D, et al: Varicella-zoster virus (chickenpox) infection in pregnancy. BJOG 118:1155, 2011a Lamont RF, Sobel JD, Vaisbuch E, et al: Parvovirus B19 infection in human pregnancy. BJOG 118(2):175, 2011b


Obstentrics_Williams

Obstentrics_Williams. Lamont RF, Sobel JD, Vaisbuch E, et al: Parvovirus B19 infection in human pregnancy. BJOG 118(2):175, 2011b Lassen J, Jensen AK, Bager P, et al: Parvovirus B19 infection in the first trimester of pregnancy and risk of fetal loss: a population-based case-control study. Am J Epidemiol 176(9):803,t2012 Lee IW, Kang L, Hsu HP, et al: Puerperal mastitis requiring hospitalization during a nine-year period. Am J Obstet Gynecol 203:332.e 1, 20J0 Leruez-Ville M, Ghout I, Bussieres L, et al: In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicenter, open-label, phase II study. Am J Obstet Gynecol 215(4):462.e1, 2016 Leruez-Ville M, Magny JF, Couderc S, et al: Risk factors for congenital cytomegalovirus infection following primary and nonprimary maternal infection: a prospective neonatal screening study using polymerase chain reaction in saliva. Clin Infect Dis 65(3):398, 2017


Obstentrics_Williams

Obstentrics_Williams. Liu C, Bayer A, Cosgrove SE, et al: Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 52:e18,t2011 Lynberg 'v[C, Khoury MJ, Lu X, et al: Maternal lu, fever, and the risk of neural tube defects: a population-based case-control study. Am J Epidemiol 140:244, 1994 Mace E, Arguin PM: Malaria Surveillance-United States, 2014. MMWR 66(12):1, 2017 Mace G, Sauvan M, Castaigne V, et al: Clinical presentation and outcome of 20 fetuses with parvovirus B 19 infection complicated by severe anemia and/ or fetal hydrops. Prenat Diagn 34(11):1023, 2014 Machado Filho AC, da Costa EP, da Costa EP, et al: Efects of vivx malaria acquired before 20 weeks of pregnancy on subsequent changes in fetal growth. Am J Trop Med Hyg 90(2):371,t2014


Obstentrics_Williams

Obstentrics_Williams. Machado Filho AC, da Costa EP, da Costa EP, et al: Efects of vivx malaria acquired before 20 weeks of pregnancy on subsequent changes in fetal growth. Am J Trop Med Hyg 90(2):371,t2014 Madhi SA, Cudand CL, Jose L, et al: Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in healthy women and their infants: a randomised phase 1b/2 trial. Lancet Infect Dis 16(8): 923, 2016 Mandelbrot : Fetal varicella-diagnosis, management, and outcome. Prenat Diagn 32(6):511, 2012 Marin M, Giiris 0,Chaves SS, et al: Prevention of varicella: recommendations of the Advisoty Committee on Immunization Practices (ACIP). MM'R 56(4):1,t200 Marin M, Willis ED, Marko A, et al: Closure of varicella-zoster viruscontaining vaccines pregnancy registry-United States. MMWR 22:63, 20t14


Obstentrics_Williams

Obstentrics_Williams. Marin M, Willis ED, Marko A, et al: Closure of varicella-zoster viruscontaining vaccines pregnancy registry-United States. MMWR 22:63, 20t14 Marzec NS, Bessesen MT: Risk and outcomes of methicillin-resistant Staphylococcus au reus (tvIRSA) bacteremia among patients admitted with and without MRSA nares colonization. Am J Infection Control 44:405, 2016 Mayama M, Yoshihara M, Kokabu T, et al: Hemophagocytic Iymphohistiocyrosis associated with a parvovirus B 19 infection during pregnancy. Obstet Gynecol 124(Pt 2 Suppl 1):438,t2014 Mayor A, Bardajf A, Macete E, et al: Changing trends in P. falciparum burden, immunity, and disease in pregnancy. N Engl J Med ):1607,t2015 McClure EM, Goldenberg RL: Infection and stillbirrh. Semin Fetal Neonatal Med 14(4):182,t2009 McClure EM, Goldenberg L, Dent E, et al: A systematic review of the impact of malaria prevention in pregnancy on low birth weight and maternal anemia. Int J Gynaecol Obstet 121:103,t2013


Obstentrics_Williams

Obstentrics_Williams. McClure EM, Goldenberg L, Dent E, et al: A systematic review of the impact of malaria prevention in pregnancy on low birth weight and maternal anemia. Int J Gynaecol Obstet 121:103,t2013 McLean HQ, Fiebelkorn AP, Temte JL, et al: Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: summary recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 62(4):1,t2013 Meaney-Delman 0, Oduyebo T, Polen KN, et al: Prolonged detection ofZika virus RNA in pregnant women. Obstet Gynecol 128(4):724,t2016 Meaney-Delman 0, Rasmussen SA, Beigi RH, et al: Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 122(4):885,t2013 Meaney-Delman 0, Zotti ME, Rasmussen SA, et al: Anthrax cases in pregnant and postpartum women. Obstet GynecoIt120(6):1439, 2012


Obstentrics_Williams

Obstentrics_Williams. Meaney-Delman 0, Zotti ME, Rasmussen SA, et al: Anthrax cases in pregnant and postpartum women. Obstet GynecoIt120(6):1439, 2012 Meijer J,van NoortwijkAG, Bruinse HW, et al: Influenza virus infection in pregnancy: a review. Acta Obstet Gynecol Scand 94(8):797,t2015 Melamed N, Whittle W, Kelly EN, et al: Fetal thrombocytopenia in preg nancies with fetal human parvovirus-B19 infection. Am J Obstet Gynecol 212:793.e1,t2015 Mendelson E, Aboundy Y, Smetana Z, et al: Laboratory assessment and diagnosis of congenital viral infections: rubella, cytomegalovirus (CMV) , varicella-zoster virus (VZV) , herpes simplex virus (HSV), parvovirus B 19 and human immunodeficiency virus (HI). Reprod Toxicol 21:350,2006 Menendez C, D'Alessandro U, ter Kuile FO: Reducing the burden of malaria in pregnancy by preventive strategies. Lancet Infect Dis 7: 126, 2007


Obstentrics_Williams

Obstentrics_Williams. Menendez C, D'Alessandro U, ter Kuile FO: Reducing the burden of malaria in pregnancy by preventive strategies. Lancet Infect Dis 7: 126, 2007 Mertz 0, Geraci J, Winkup J, et al: Pregnancy as a risk factor for severe outcomes from inluenza virus infection: a systematic review and meta-analysis of observational studies. Vaccine 35(4):521, 2017 Miller E, Cradock-Watson JE, Pollock TM: Consequences of conirmed maternal rubella at successive stages of pregnancy. Lancet 2:781, 1982 Miller LG, Daum RS, Creech CB, et al: Clindamycin versus trimethoprimsulfamethoxazole for uncomplicated skin infections. N Engl J Med 372(12):1093,t2015 Modlin F: Perinatal echovirus and group B coxsackievirus infections. Clin PerinatoIt15:233, 1988 Money 0, Infectious Disease Committee Members, Yudin MH, et al: SOBC committee opinion on the management of a pregnant woman exposed to or infected with Ebola virus disease in Canada. J Obstet Gynaecol Can 37(2):182,t2015


Obstentrics_Williams

Obstentrics_Williams. Montazeri M, Sharif M, Sarvi S, et al: A systematic review of in vitro and in vivo activities of anti-toxoplasma drugs and compounds (2006-2016). Front Microbiol 8(25): 1, 2017 Montoya JG, Remington JS: Management of Toxoplasma gondii infection during pregnancy. Clin Infect Dis 47:554, 2008 Moore CA, Staples JE, Dobyns B, et al: Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr 171(3):288,t2017 Moschella SL: An update on the diagnosis and treatment ofleprosy. J Am Acad Dermatol 51 :417, 2004 Muehlenbachs A, de la Rosa Vazquez 0, Bausch DG, et al: Ebola virus disease in pregnancy: clinical, histopathologic, and immunohistochemical findings. J Infect Dis 215(1):64, 2017 Mylonakis E, Paliou M, Hohmann EL, et al: Listeriosis during pregnancy. Medicine 81 :260, 2002 Mylonas I: Borreliosis during pregnancy: a risk for the unborn child? Vector Borne Zoonotic Dis 11(7):891,t2011


Obstentrics_Williams

Obstentrics_Williams. Medicine 81 :260, 2002 Mylonas I: Borreliosis during pregnancy: a risk for the unborn child? Vector Borne Zoonotic Dis 11(7):891,t2011 Nagel HT, de Haan TR, Vandenbussche FP, et al: Long-term outcome after fetal transfusion for hydrops associated with parvovirus B 19 infection. Obstet Gynecol 109(1):42,t2007 Nan e, Dangor Z, Cutland CL: Maternal group B streptococcus-related stillbirth: a systematic review. BJOG 122(11):1437,t2016 Nguyen LN, Lopes e, Folk JJ: vertebral osteomyelitis in pregnancy from a methicillin-resistant Staphylococcus aureus vulvar abscess. A case report. J Reprod Med 60(7-8):362,t2015 Nigro G, Adler SP, La Torre R, et al: Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 353:1350,t2005


Obstentrics_Williams

Obstentrics_Williams. Nigro G, Adler SP, La Torre R, et al: Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 353:1350,t2005 Nigro G, Adler SP, Parruti G, et al: Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy-a case-control study of the outcome in children. J Infect Dis 205:215, 2012 Nigro G, Anceschi MM, Cosmi EV, et al: Clinical manifestations and abnormal laboratory findings in pregnant women with primary cytomegalovirus infection. BJOG 110:572,t2003 Nishiura H: Smallpox during pregnancy and maternal outcomes. Emerg Infect Dis 12:1119,t2006 Nosten F, McGready R, Mutabingwa T: Case management of malaria in pregnancy. Lancet Infect Dis 7:118,t2007 Nunes Me, Cutland CL, Jones S, et al: Eicacy of maternal influenza vaccination against all-cause lower respiratory tract infection hospitalizations in young infants: results from a randomized control trial. Clin Infect Disease May 29, 2017 [Epub ahead of print]


Obstentrics_Williams

Obstentrics_Williams. O'Leary DR, Kuhn S, Kniss L, et al: Birth outcomes following West Nile virus infection of pregnant women in the United States: 2003-2004. Pediatrics 117:e537, 2006 Oboho IK, Reed C, Gargiullo P, et al: Benefit of early initiation of influenza antiviral treatment to pregnant women hospitalized with laboratoryconfirmed influenza. J Infect Dis 214(4):507, 2016 Oduyebo T, Pineda 0, Lamin M, et al: A pregnant patient with Ebola virus disease. Obstet GynecoIt126(6):1273, 2015 Oduyebo T, Polen KD, Walke HT, et al: Update: interim guidance for health care providers caring for pregnant women with possible Zika virus exposure-United States (including U.S. Territories), July 2017. MMWR 66(29):781, 2017 Ohji G, Satoh H, Satoh H, et al: Congenital measles caused by transplacental infection. Pediatr Infect Dis J 28(2): 166, 2009 Ohlsson A, Shah VS: Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database Syst Rev (6):CD007467, 2014


Obstentrics_Williams

Obstentrics_Williams. Ohlsson A, Shah VS: Intrapartum antibiotics for known maternal Group B streptococcal colonization. Cochrane Database Syst Rev (6):CD007467, 2014 Ornoy A, Tenenbaum A: Pregnancy outcome following infections by coxsackie, echo, measles, mumps, hepatitis, polio and encephalitis viruses. Reprod ToxicoIt21:446, 2006 Ozturk Z, Tatliparmak A: Leprosy treatment during pregnancy and breastfeeding: a case report and brief review of literature. Dermatol her 30(1): 1,2017 Parisot M, Jolivet A, Boukhari R, et al: Shigellosis and pregnancy in French Guiana: obstetric and neonatal complications. Am J Trop Med Hyg 95(1):26,t2016 Parra B, Lizarazo J, Jimenez-Arango JA, et al: Guillain-Barre syndrome associated with Zika virus infection in Colombia. N Engl J Med 375(16):1513, 2016 Paryani SG, Arvin AM: Intrauterine infection with varicella zoster virus ater maternal varicella. N Engl J Med 314:1542, 1986


Obstentrics_Williams

Obstentrics_Williams. Paryani SG, Arvin AM: Intrauterine infection with varicella zoster virus ater maternal varicella. N Engl J Med 314:1542, 1986 Pasquini L, Seravilli V, Sisti G, et al: Prevalence of a positive TORCH and parvovirus B19 screening in pregnancies complicated by polyhydramnios. Prenat Diagn 36(3):290, 2016 Paz-Bailey G, Rosenberg ES, Doyle K, et al: Persistence of Zika virus in body fluids-preliminary report. N Engl J Med February 14, 2017 [Epub ahead of print] Peques DA, Miller SI: Salmonellosis. In Longo DL, Fauci AS, Kasper DL, et al (eds): Harrison's Principles of Internal Medicine, 18th ed. New York, McGraw-Hill Phadke K, Bednarczyk A, Salmon DA, et al: Association between vaccine refusal and vaccine-preventable diseases in the United States. JAMA 315(11):1149,t2016 Picone 0, Grangeot-Keros L, Senat M, et al: Cytomegalovirus non-primary infection during pregnancy. Can serology help with diagnosis? J Matern Fetal Neonatal Med 30(2):224, 2017


Obstentrics_Williams

Obstentrics_Williams. Picone 0, Grangeot-Keros L, Senat M, et al: Cytomegalovirus non-primary infection during pregnancy. Can serology help with diagnosis? J Matern Fetal Neonatal Med 30(2):224, 2017 Pimentel JD, Meier FA, Samuel LP: Chorioamnionitis and neonatal sepsis from community-acquired MRSA. Emerg Infect Dis 15:2069,t2009 Pinter OM, Mandel J, Hulten KG, et al: Maternal-infant perinatal transmission of methicillin-resistant and methicillin-sensitive Staphylococcus aureus. Am J PerinatoIt26:145, 2009 Polyzos A, Konstantelias A, Pitsa CE, et al: Maternal influenza vaccination and risk for congenital malformations: a systematic review and metaanalysis. Obstet Gynecol 126(5):1075,t2015 PREGACT Study Group, Pekyi 0, Ampromfi A, et al: Four artemisininbased treatments in African pregnant women with malaria. N Engl J Med 374(1):913,t2016


Obstentrics_Williams

Obstentrics_Williams. PREGACT Study Group, Pekyi 0, Ampromfi A, et al: Four artemisininbased treatments in African pregnant women with malaria. N Engl J Med 374(1):913,t2016 Pridjian G, Sirois PA, McRae S, et al: Prospective study of pregnancy and newborn outcomes in mothers with West Nile illness during pregnancy. Birth Oefects Res A Clin Mol Teratol 106(8):716,t2016 Puccetti e, Contoli M, Bonvicini F, et al: Parvovirus B19 in pregnancy: possible consequences of vertical transmission. Prenat Diagn 32(9):897, 2012 Rainwater-Lovett K, Moss WJ: Measles (rubeola). In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Internal Medicine, 19th ed. New York, McGraw-Hill, 2015 Randis TM, Gleber SE, Hooven TA: Group B streptococcus beta-hemolysin/ cytolysin breaches maternal-fetal barriers to cause preterm birth and IUFO in vivo. J Infect Ois 210:65, 2014 Rasmussen SA, Jamieson OJ: What obstetric health care providers need to know about measles and pregnancy. Obstet GynecoIt126(1):163, 2015


Obstentrics_Williams

Obstentrics_Williams. Rasmussen SA, Jamieson OJ: What obstetric health care providers need to know about measles and pregnancy. Obstet GynecoIt126(1):163, 2015 Rasmussen SA, Jamieson OJ, Honein MA, et al: Zika virus and birth defects-reviewing the evidence for causality. N Engl J Med 374(20): 1981, 2016 Rasmussen SA, Jamieson OJ, Uyeki TM: Efects of inluenza on pregnant women and infants. Am J Obstet Gynecol 207(3 Suppl):S3, 2012 Revello MG, Furione M, Zavattoni M, et al: Human cytomegalovirus (HCMV) DNAemia in the mother at amniocentesis as a risk factor for iatrogenic HCMF infection of the fetus. ] Infect Dis :593, 2008 Reynolds MR, Jones AM, Peterson EE, et al: Vital signs: Update on Zika virus-associated birth defects and evaluation of all U.S. infants with congenital Zika virus exposure-U.S. Zika pregnancy registry, 2016. MMWR 66(13):366t2017 Rogers BB: Parvovirus B 19: twenty-five years in perspective. Pediatr Dev Pathol 2:296, 1999


Obstentrics_Williams

Obstentrics_Williams. Rogers BB: Parvovirus B 19: twenty-five years in perspective. Pediatr Dev Pathol 2:296, 1999 Rogerson S], Hviid L, Duy PE, et al: Malaria in pregnancy: pathogenesis and immunity. Lancet Infect Dis 7: 105, 2007 Romand S, Wallon M, Franckt], et al: Prenatal diagnosis using polymerase chain reaction on amniotic luid for congenital toxoplasmosis. Obstet Gynecol 97(2):296, 2001 Ross SA, Novak Z, Pati S, et al: Mixed infection and strain diversity in congenital cytomegalovirus infection. ] Infect Dis 204: 1 003, 2011 Rouse D], Keimig W, Riley LE, et al: Case Records of the Massachusetts General Hospital. Case 16-2016. A 31-year-old pregnant woman with fever. N Engl] Med 4(21):2076,t2016 Rubin S, Carbone M: Mumps. In Longo DL, Fauci AS, Kasper DL, et al (eds): Harrison's Principles of Internal Medicine, 18th ed. New York, McGraw-Hill,t2012 Ryan MA, Smith TC, Sevick C]: Birth defects among infants born to women who received anthrax vaccine in pregnancy. Amt] EpidemioIt168:434, 2008


Obstentrics_Williams

Obstentrics_Williams. Ryan MA, Smith TC, Sevick C]: Birth defects among infants born to women who received anthrax vaccine in pregnancy. Amt] EpidemioIt168:434, 2008 Sanchez E, Vannier E, Wormser GP, et al: Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a review.t]MA 315(16):1 67,t2016 Sapuan S, Kortsalioudaki C, Anthony M, et al: Neonatal listeriosis in the UK 2004-2014.t] Infect 74(3):236,t201 Schleiss MR: Cytomegalovirus vaccines under clinical development. J Virus Erad 2(4):198, 2016 Schrag 5], Farley MM, Petit S: Epidemiology of invasive early-onset neonatal sepsis, 2005-2014. Pediatrics 138(6):e20162013, 2016 Sever ]L, South MA, Shaver A: Delayed manifestations of congenital rubella. Rev Infect Dis 7(1):S164, 1985 Shang M, Blanton L, Kniss K, et al: Update: influenza activity-United States, October 2-December 17,t2016. MMWR 65(5051):1439,2016 Shapiro ED: Lyme disease. N Engl] Med 370(18):1 24,2014


Obstentrics_Williams

Obstentrics_Williams. Shang M, Blanton L, Kniss K, et al: Update: influenza activity-United States, October 2-December 17,t2016. MMWR 65(5051):1439,2016 Shapiro ED: Lyme disease. N Engl] Med 370(18):1 24,2014 Shaw GM, Todorof K, Velie EM, et al: Maternal illness, including fever, and medication use as risk factors for neural tube defects. Teratology 57: 1, 1998 Sheield ]S: Methicillin-resistant Staphylococcus aureus in obstetrics. An ] PerinatoIt30(2):125,t2013 Shinar S, Fouks Y, Anit S, et al: Clinical characteristics of and preventative strategies for periparrum group A streptococcal infections. Obstet Gynecol 127(2):227,t2016 Siegel M: Congenital malformations following chickenpox, measles, mumps, and hepatitis: results of a cohort study. ]AMA 226: 1521, 1973 Siegel M, Goldberg M: Incidence of poliomyelitis in pregnancy. N Engl] Med 253:841,t1955 Silk B], Mahon BE, Griin PM, et al: Vital signs: Listeria illness, deaths, and outbreaks-United States, 2009-2011t. MMWR 62(22):448,2013


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Obstentrics_Williams. Silk B], Mahon BE, Griin PM, et al: Vital signs: Listeria illness, deaths, and outbreaks-United States, 2009-2011t. MMWR 62(22):448,2013 Soares de Oliveira-Szejnfeld P, Levine D, Melo AS, et al: Congenital brain abnormalities and Zika virus: what the radiologist can expect to see prenatally and postnatally. Radiology 2810):203, 2016 Society for Maternal-Fetal Medicine (SMFM), Hughes BL, Gyami-Bannerman C: Diagnosis and antenatal management of congenital cytomegalovirus infection. Am] Obstet Gynecol 214(6):B5, 2016 Staford LA, Stewart RD, Sheield ]S, et al: Eicacy of maternal and neonatal chemoprophylaxis for early-onset group B streptococcal disease. Obstet Gynecol 120(1):123,t2012 Stagno S, Tinker MK, Elrod C, et al: Immunoglobulin M antibodies detected by enzyme-linked immunosorbent assay and radioimmunoassay in the diagnosis of cytomegalovirus infections in pregnant women and newborn infants. ] C1in Microbiol 21 (6):930, 1985


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Obstentrics_Williams. Steere AC: Lyme borreliosis. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Internal Medicine, 19th ed. New York, McGrawHill,t2015 Steinhof MC, Omer SB: A review of fetal and infant protection associated with antenatal inluenza immunization. Am J Obstet Gynecol 207(3 Suppl): S21,t2012 Stewart RD, Bryant SN, Sheield ]S: West Nile virus infection in pregnancy. Case report. Infect Dis 2013:351872, 2013 Stoll B], Hansen NI, Sanchez P], et al: he burden of group B streptococcal and E. coli disease continues. Pediatrics ,201t1 Sukumaran L, McCarthy NL, Kharbanda EO, et al: Safety of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis and inluenza vaccinations in pregnancy. Obstet Gynecol 126(5): 1069, 2015 Svensson-Arvelund], Ernerudh], Buse E, et al: he placenta in toxicology. Part II: systemic and local immune adaptations in pregnancy. T oxicol Pathol ,2014


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Obstentrics_Williams. Svensson-Arvelund], Ernerudh], Buse E, et al: he placenta in toxicology. Part II: systemic and local immune adaptations in pregnancy. T oxicol Pathol ,2014 Swamy GK, Heine RP: Vaccinations for pregnant women. Obstet Gynecol 125(1):212,t2015 SYROCOT (Systematic Review on Congenital Toxoplasmosis) Study Group: Efectiveness of prenatal treatment for congenital toxoplasmosis: a metaanalysis of individual patients' data. Lancet 369: 115, 2007 Talan DA, Mower WR, Krishnadasan A, et al: Trimethoprim-sulfamethoxazole versus placebo for uncomplicated skin abscess. N Engl ] Med 374(9):823, 2016 Tanamai VW, Seagle BL, Luo G: Methicillin-resistant Staphylococcus aureus intracranial epidural abscess with osteomyelitis during pregnancy: a case report.t] Reprod Med 61(5-6):295,t2016 Tarningt]: Treatment of malaria in pregnancy. N Engl ] Med 374(1):981, 2016


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Obstentrics_Williams. Tarningt]: Treatment of malaria in pregnancy. N Engl ] Med 374(1):981, 2016 Tassin M, Martinovic ], Mirand A, et al: A case of congenital echovirus 11 infection acquired early in pregnancy.] Clin Virol 59:71, 2014 Thurman AR, Satterield RM, Soper DE: Methicillin-resistant Staphylococcus aureus as a common cause of vulvar abscesses. Obstet Gynecol 112:538, 2008 Top A, Huard RC, Fox Z, et al: Trends in methicillin-resistant Staphylococcus aureus anovaginal colonization in pregnant women in 2005 versus 2009. ] C1in Microbiol 48:3675, 2010 Towbin ]A, Griin LD, Martin AB, et al: Intrauterine adenoviral myocarditis presenting as nonimmune hydrops fetalis: diagnosis by polymerase chain reaction. Pediatr Infect Dis] 13:144, 1994 Tudela CM, Stewart RD, RobertS SW, et al: Intrapartum evidence of earlyonset group B streptococcus. Obstet Gynecol 119(3):626,t2012


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Obstentrics_Williams. Tudela CM, Stewart RD, RobertS SW, et al: Intrapartum evidence of earlyonset group B streptococcus. Obstet Gynecol 119(3):626,t2012 Valentini P, Buonsenso 0, Barone G, et al: Spiramycin/cotrimoxazole versus pyrimethamine/sulfonamide and spiramycin alone for the treatment of toxoplasmosis in pregnancy. ] Perinatol 35(2):90, 2015 Villard 0, Breit L, Cimon B, et al: Comparison of four commercially available avidity tests for Toxoplasma gondii-speciic IgG antibodies. Clin Vaccine ImmunoIt20(2):197,t2013 Visentin S, Manara R, Milanese L, et al: Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age. Clin Infect Dis 55(4):497, 2012


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Obstentrics_Williams. Viskari H, Knip M, Tauriainen S, et al: Maternal enterovirus infection s a risk factor for type 1 diabetes in the exposed ofspring. Diabetes Care 35(6): 1328,t2012 Wallon M, Gatweg ]G, Abrahamowicz M, et al: Ophthalmic outcomes of congenital toxoplasmosis followed until adolescence. Pediatrics 133(3):e601, 2014 Wallon M, Peyron F, Cornu C, et al: Congenital toxoplasma infection: monthly prenatal screening decreases transmission rate and improves clinical outcome at age 3 years. Clin Infect Dis 56(9):1223, 2013 Walsh CA, Mayer EQ, Baxi LV: Lyme disease in pregnancy: case report and review of the literature. Obstet Gynecol Surv 62:41, 2006 Wang C, Zhang X, Bialek S, et al: Attribution of congenital cytomegalovirus infection to primary versus non-primary matenal infection. Clin Infect Dis 52:e11,t2011 Waner M], Ozanne SE: Mechanisms involved in the developmental programming of adulthood disease. Biochem] 427:333, 2010 Webster WS:


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Obstentrics_Williams. Waner M], Ozanne SE: Mechanisms involved in the developmental programming of adulthood disease. Biochem] 427:333, 2010 Webster WS: Teratogen update: congenital rubella. Terarology 58:13,t1998 Weifenbach], Bald R, Gloning KP, et al: Serological and virological analysis of maternal and fetal blood samples in prenatal human parvovirus B 19 infection. ] Infect Dis 205(5):782, 2012 Wendel GO Jr, Leveno K], Sanchez P], et al: Prevention of neonatal group B streptococcal disease: a combined intrapartum and neonatal protocol. Am ] Obstet Gynecol 186:618,t2002 Wessels MR: Streptococcal infections. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Intenal Medicine, 19th ed. New York, McGraw-Hill,t2015 White N], Breman ]G: Malaria infections. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Intenal Medicine, 19th ed. New York, McGraw-Hill,t2015


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Obstentrics_Williams. White N], Breman ]G: Malaria infections. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Intenal Medicine, 19th ed. New York, McGraw-Hill,t2015 Whitley R]: Varicella-zoster virus infections. In Kasper DL, Fauci AS, Hauser SL, et al (eds): Harrison's Principles of Intenal Medicine, 19th ed. New York, McGraw-Hili, 2015 Wilson E, Goss vA, Marin M, et al: Varicella vaccine exposure during pregnancy: data from 10 years of the pregnancy registry.] Infect Dis 197(Suppl 2): Sl78, 2008 Wong SF, Chow M, Leung TN, et al: Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome. Am ] Obstet Gynecol 191:292,t2004 World Health Organization: Long-term efects of breastfeeding: a systematic review, 2013. Available at: htrp:l /ww.who.int/maternal_child_adolescent/ documents/breastfeedingJon�term_efects. Accessed October 9, 20t17


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Obstentrics_Williams. World Health Organization: WHO vaccine pipeline tracker, 2017. Available at: www.who.int/immunization/ research/vaccine_pi peline_trackecspreadsheet/en.! Accessed September 10,t2017 Wylie B, Hauptman M, Woolf AD: Inset repellants during pregnancy in the era of the Zika virus. Obstet Gynecol 128(5): 1111,t2016 Yaegashi N: Pathogenesis of nonimmune hydrops fetalis caused by intrauterine B19 infection. Tohoku] Exp Med 190:65,t2000 Yazigi A, De Pecoulas E, Vauloup-Fellous C, et l: Fetal and neonatal abnormalities due to congenital rubella syndrome: a review of literature. ] Matern Fetal Neonatal Med 30(3):274,t2017 Young MK, Cripps AW, Nimmo GR, et al: Post-exposure passive immunization for preventing rubella and congenital rubella syndrome. Cochrane Database Syst Rev 9:CD010586, 2015


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Obstentrics_Williams. Young MK, Cripps AW, Nimmo GR, et al: Post-exposure passive immunization for preventing rubella and congenital rubella syndrome. Cochrane Database Syst Rev 9:CD010586, 2015 Yu W, Tellier R, Wright]R]: Coxsackie virus A16 infection of placenta with massive perivillous ibrin deposition leading to intrauterine fetal demise at 36 weeks gestation. Pediatr Dev Pathol 18(4):331,t2015 Zaman K, Roy E, Arifeen SE, et al: Efectiveness of maternal influenza immunization in mothers and infants. N Engl ] Med 359(15):1555, 2008 Zerbo 0, Qian Y, Yoshida C, et al: Association berween inluenza infection and vaccination during pregnancy and risk of autism spectrum disorder. ]AlA Pediarr 171(1):e163609, 2017 Zhang H], Patenaude V, Abenhaim A: Maternal outcomes in pregnancies afected by varicella zoster virus infections: population-based study on 7.7 million pregnancy admissions. ] Obstet Gynaecol Res 41(1):62, 2015


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Obstentrics_Williams. SYPHILIS.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1235 GONORRHEA.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1239 CHLAMYDIAL.INFECTIONS . . . . . . . . . . . . . . . . . . . . .. 1240 HERPES SIMPLEX VIRUS . . . . . . . . . . . . . . . . . . . . . . .. 1241 HUMAN PAPILLOMAVIRUS ............i.......i...i...i. 1244 VAGINITIS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 1245 HUMAN IMMUNODEFICIENCY VIRUS .....i....i...i... 1247 Syphilis is one of the most important complications of preg nancy, as it is one of the most frequent causes of abortion or premature labour. Syphilis is the most common cause of oetal death in the later months of pregnancy, and may be maternal or paternal in origin. -J. Whitridge Williams (1903)


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Obstentrics_Williams. -J. Whitridge Williams (1903) Syphilis and gonorrhea were prominently mentioned in the irst edition of this book, with special consideration for their harmful efects on fetal development. Although Williams confined his discussion to these two infections, today, sexually transmitted diseases (STDs) include chlamydial and trichomonal infections and viral STDs such as hepatitis B, human immunodeiciency virus (HIV), herpes simplex virus (HSV), and human papillomavirus (HPV) infections. In some form, all can be injurious to the mother or fetus and thus should be aggressively sought and treated. In many instances, recommended therapies are provided in guidelines from the Centers for Disease Control and Prevention (CDC) and listed throughout the chapter.


Obstentrics_Williams

Obstentrics_Williams. Vertical transmISSIOn refers to passage from the mother to her fetus of an infectious agent through the placenta, during labor or delivery, or by breastfeeding. Treatment of most STDs is clearly associated with improved pregnancy outcome and prevention of perinatal morbidity. Logically, education, screening, treatment, and prevention are essential components of prenatal care.


Obstentrics_Williams

Obstentrics_Williams. Despite the availability of adequate therapy for decades, syphilis remains a major issue for both mother and fetus. From 2001 through 2015, the primary and secondary syphilis rates have risen almost yearly (Centers for Disease Control and Prevention, 2016c). In the United States in 2015, the combined rate for both of these among women was 1.8 cases per 100,000 persons (de Voux, 2017). For congenital syphilis, after a nadir in 2012, rates have also risen yearly to reach 12.4 cases per 100,000 live births in 2015. Of risks, higher congenital syphilis rates are linked to inadequate prenatal care, black or Hispanic race, and lack of treatment (Su, 2016). Similarly, syphilis remains a signiicant global health problem, with many countries reporting high numbers of new infections (Newman, 2015; World Health Organization, 2012).


Obstentrics_Williams

Obstentrics_Williams. Syphilis is caused by the spirochetal bacterium Treponema pallidum. Minute abrasions on the vaginal mucosa provide an entry portal, and cervical eversion, hyperemia, and friability raise transmission risk. Spirochetes replicate and then disseminate through lymphatic channels within hours to days. The incubation period is 3 to 4 weeks depending on host factors and inoculum size. he early stages of syphilis include primary, secondary, and early latent syphilis. hese are associated with high spirochete loads, and partner transmission rates approximate 30 to 60 percent (Garnett, 1997; Singh, 1999). In late-stage disease, transmission rates decline because of smaller inoculum sizes. FIGURE 65-1 Primary syphilis. Photograph of a chancre with a raised, firm border and smooth, red base.


Obstentrics_Williams

Obstentrics_Williams. FIGURE 65-1 Primary syphilis. Photograph of a chancre with a raised, firm border and smooth, red base. Maternal syphilis can cause fetal infection by several routes. Spirochetes readily cross the placenta to cause congenital infection. Although transplacental transmission is the most common route, neonatal infection may follow after contact with spirochetes through lesions at delivery or across the placental membranes. Fetal infection develops in >50 percent of untreated early syphilis cases and in 10 percent of late latent disease (Fiumara, 1975; Hollier, 2001). This is staged according to clinical features and disease duration. 1. Primary syphilis is diagnosed by its characteristic chancre, which develops at the inoculation site. This solitary, painless


Obstentrics_Williams

Obstentrics_Williams. This is staged according to clinical features and disease duration. 1. Primary syphilis is diagnosed by its characteristic chancre, which develops at the inoculation site. This solitary, painless FIGURE 65-3 Condyloma lata. (Reproduced with permission from Horsager R, Roberts S, Roger V, et al (eds): Williams Obstetrics 24th Edition Study Guide, New York, McGraw Hill Education, 2014; Photo contributor: Dr. Jonathan Willms.) lesion typically has a raised, firm border and a red, smooth ulcerated base without signiicant pus (Fig. 65-1). Nonsuppurative lymphadenopathy may develop. A chancre will usually resolve spontaneously in 2 to 8 weeks, even if untreated. Multiple lesions, if found, are predominantly in HIV-1 coinfected women.


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Obstentrics_Williams. 2. Secondary syphilis stems from dissemination of spirochetes to afect multiple organ systems. Manifestations develop 4 to 10 weeks after the chancre appears and include dermatological abnormalities in up to 90 percent of women. A difuse macular rash, plantar and palmar targetlike lesions, patchy alopecia, and mucous patches may be seen (Fig. 65-2). Condylomata lata are flesh-colored papules and nodules found on the perineum and perianal area (Fig. 65-3). These papules are teeming with spirochetes and are highly infectious. Most women with secondary syphilis also express constitutional symptoms such as fever, malaise, headache, and myalgias. FIGURE 65-2 Secondary syphilis. A.Target lesions on the palms. B. Mucous patches around the nose and mouth. (Used with permission from Dr. Devin Macias.) Hepatitis, nephropathy, ocular changes, anterior uveitis, and periostitis can also develop. 3.


Obstentrics_Williams

Obstentrics_Williams. Hepatitis, nephropathy, ocular changes, anterior uveitis, and periostitis can also develop. 3. Latent syphilis develops when primary or secondary syphilis is not treated but clinical manifestations still resolve. It is identified instead by serological testing. Eary latent syphilis is subclinical disease acquired within the preceding 12 months. Disease diagnosed beyond 12 months is either late latent syphilis or latent syphilis of unknown duration. 4. Tertiary syphilis is a slowl) progressive disease afecting any organ system but is rarely seen in reproductive-aged women.


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Obstentrics_Williams. 4. Tertiary syphilis is a slowl) progressive disease afecting any organ system but is rarely seen in reproductive-aged women. Without screening and treatment, approximately 70 percent of infected women will have an adverse pregnancy outcome (Hawkes, 201l). Maternal infection can lead to preterm labor, fetal death, fetal-growth restriction, or fetal infection (Gomez, 2013). Because of immune incompetence prior to midpregnancy, the fetus generally does not manifest the immunological inlammatory response characteristic of clinical disease before this time (Silverstein, 1962). Once fetal syphilis develops, however, it manifests as a continuum. Fetal hepatic abnormalities are followed by anemia and thrombocytopenia, then ascites and hydrops (Hollier, 2001). Stillbirth remains a major complication (Lawn, 2016; Su, 2016). he newborn may have jaundice with petechiae or purpuric skin lesions, lymphadenopathy, rhinitis, pneumonia, myocarditis, nephrosis, or long-bone involvement (Fig. 65-4).


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Obstentrics_Williams. With syphilitic infection, the placenta becomes large and pale (see Fig. 65-4). Microscopically, villi lose their characteristic arborization and become thicker and clubbed. Sheield and colleagues (2002c) described these villi in more than 60 percent of syphilitic placentas. Blood vessels markedly diminish in number, and in advanced cases, they almost entirely disappear as a result of endarteritis and stromal cell proliferation. Likely related, Lucas and coworkers (1991) demonstrated increased vascular resistance in uterine and umbilical arteries of infected pregnancies. he cord may also show evidence of infection. In a study of 25 untreated women, Schwartz and associates (1995) reported that necrotizing funisitis was present in a third.


Obstentrics_Williams

Obstentrics_Williams. The United States Preventative Services Task Force recom mends that clinicians screen all pregnant women for syphilis to prevent congenital infection (Wolf, 2009). Testing is ideally performed at the irst prenatal visit. In populations with a high prevalence of syphilis, serological testing is repeated in the third trimester and again at delivery (Workowski, 2015). Treponema pallidum cannot be cultured from clinical specimens. However, direct diagnosis of early-stage disease from lesion exudate, tissue, or body luid can be completed by darkield microscopic examination, by polymerase chain reaction (PCR), or by direct fluorescent antibody tests for T pallidum (DFA-TP) (Tsang, 2015). hese methods are not widely available and are less sensitive for blood specimens (Grange, 2012; HenaoMartinez, 2014). hus, in practice, diagnoses are mainly derived from clinical indings coupled with serological blood testing.


Obstentrics_Williams

Obstentrics_Williams. Serological testing is used for diagnostic and for screening purposes. here are two types. If the irst of these is positive, then the second type is also performed. his combination identifies infection and clariies disease stage. Traditionally, the first type is nontreponemal testing, and either the Venereal Disease Research Laboratory (VDRL) or the rapid plasma reagin (RPR) is selected. Both tests measure patient immunoglobulin M and G (IgM and IgG) antibodies formed against cardiolipin that is released from damaged host cells and possibly also from treponemes. Notably, these same antibodies can also be produced in response to other acute events that include recent vaccination, febrile illness, and pregnancy itself or in response to chronic conditions such as intravenous drug abuse, systemic lupus erythematosus, aging, leprosy, or cancer. As such, these all serve as potential sources of false-positive results (Larsen, 1995). Conversely, seroconversion occurs at around 3 weeks, but


Obstentrics_Williams

Obstentrics_Williams. lupus erythematosus, aging, leprosy, or cancer. As such, these all serve as potential sources of false-positive results (Larsen, 1995). Conversely, seroconversion occurs at around 3 weeks, but can take up to 6 weeks (Peeling, 2004). Thus, women with very early primary syphilis can have initially false-negative serological test results.


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Obstentrics_Williams. FIGURE 65-4 Congenital syphilis. A. Fetogram of a stillborn infant infected with syphilis showing the "moth-eaten" appearance of the femurs (arrow). B. Enlarged hydropic placenta of a syphilis-infected neonate.


Obstentrics_Williams

Obstentrics_Williams. With positive nontreponemal test results, findings are quantified and expressed as titers. Because titers reflect disease activity, they increase during early syphilis and often exceed levels of 1 :32 in secondary syphilis. Following treatment of primary and secondary syphilis, serological testing at 3 to 6 months usually confirms a fourfold drop in VDRL or RPR titers (Rac, 2014a). Because VDRL titers do not correspond directly to RPR titers, consistent use of the same test for surveillance is recommended. hose with treatment failure or reinfection may lack this expected decline. Importantly, some successfully treated patients may still exhibit persistently low-level positive titers, which are referred to as "serofast." his state is more likely in older individuals, those with lower initial nontreponemal antibody titers, and those with later stages of syphilis (Seia, 2015). The second type of serological testing is trep0 nemal-specic.


Obstentrics_Williams

Obstentrics_Williams. The second type of serological testing is trep0 nemal-specic. It seeks patient antibodies formed specifically against T palidum. he antibodies detected by treponemal assays appear up to a few weeks earlier than those detected by nontreponemal tests (Levett, 2015). Tests includes the fluorescent treponemalantibody absorption tests (FTA-ABS), the T palidum passive particle agglutination (TP-PA) test, and various immunoassays (Association of Public Health Laboratories, 2015). O/note, these treponemal-speciic tests generaly remain positive throughout lie.


Obstentrics_Williams

Obstentrics_Williams. Each of the serological tests has limitations including falsepositive and -negative results. Traditionally, nontreponemal tests have been used for screening in the United States, and results are then conirmed by a specific treponemal test. Within the past several years, some laboratories have implemented a reverse screening algorithm, namely, screening first with a treponemalspecific test (Binnicker, 2012; Centers for Disease Control and Prevention, 2011). Both approaches are efective if there is a program for appropriate screening, follow-up, and treatment.


Obstentrics_Williams

Obstentrics_Williams. In contrast to these tests, rapid "point-of-care" (POC) syphilis screening of blood or serum samples is being developed (Singh, 2015; Tucker, 2010). hese may be best used for women with limited prenatal care. Most tests are treponemalspecific, and positive POC results can then be confirmed by a laboratory nontreponemal test. In hard-to-reach populations, some countries immediately treat women with positive POC results. This practice, however, risks overtreating previously cured women who still have residual persistent treponemal antibodies. his limitation may be overcome by newer POC dual tests, which simultaneously assess nontreponemal and treponemal antibodies (Causer, 2015).


Obstentrics_Williams

Obstentrics_Williams. Following maternal diagnosis, sonographic evaluation is performed for fetuses >20 weeks' gestation to search for signs of congenital syphilis. Rac and associates (20 14b) noted that 31 percent of infected women diagnosed at � 18 weeks' gestation had abnormal fetal sonographic indings. Hepatomegaly, placental thickening, hydramnios, ascites, hydrops fetalis, and elevated middle cerebral artery Doppler velocimetry measurements are indicative of fetal infection. Before 20 weeks, treatment is highly successful, and sonographic findings are rare (Nathan, 1997).


Obstentrics_Williams

Obstentrics_Williams. For fetuses of viable age with sonographic findings, antepartum fetal heart rate monitoring prior to treatment is recommended. Spontaneous late decelerations or a nonreactive tracing likely reflects an extremely ill fetus that may poorly tolerate a Jarisch-Herxheimer reaction, described next. In this extreme case, consultation with a neonatologist regarding a plan of delaying treatment, pursuing delivery, and then treating in the nursery is a consideration (Wendel, 2002). Syphilis therapy during pregnancy is given to eradicate maternal infection and to prevent or treat congenital syphilis. Parenteral penicillin G remains the preferred treatment for all stages of syphilis during pregnancy (Table 65-1). During pregnancy, authorities recommend that a second dose of benzathine penicillin G be given 1 week after the initial dose. Such treatment is also given for women with concomitant HIV infection (Workowski, 2015).


Obstentrics_Williams

Obstentrics_Williams. Benzathine penicillin G is highly efective for early maternal infection. In a study of 340 pregnant women so treated, Alexander and associates (1999) reported six cases-1.8 percent-of congenital syphilis. Four of these six neonates were from a group of75 women with secondary syphilis. The other two were identified in those delivered from a group of 102 women with early latent syphilis. Congenital syphilis was generally confined to neonates of women treated ater 26 weeks and is likely related to the duration and severity of fetal infection. Sheield and coworkers (2002b) reported that high maternal serological titers, preterm delivery, and delivery shortly ater antepartum therapy are all risks for failure of maternal treatment to prevent neonatal infection.


Obstentrics_Williams

Obstentrics_Williams. here are no proven alternatives to penicillin therapy during pregnancy. Erythromycin and azithromycin may be curative for the mother, but because of limited transplacental passage, these drugs do not prevent all congenital disease (Berman, 2004; Wendel, 1988; Zhou, 2007). Moreover, in several countries, TABLE 65-1. Recommended Treatment for Pregnant Women with Syphilis G, 2.4 million units as a single injection-some recommend a second More than l-year durationb Benzathine penicillin G, 2.4 million units intramuscularly weekly for three doses aprimary, secondary, early latent syphilis of less than duration. bLatent syphilis of unknown or more than 1-year duration; tertiary syphilis. Missed doses are not acceptable for pregnant women, and those who miss any dose of therapy must repeat the full course of therapy. Data from Workowski, 201r5.


Obstentrics_Williams

Obstentrics_Williams. Data from Workowski, 201r5. macrolide-resistant strains of T pallidum are now prevalent (Stamm, 2015). Cephalosporins may prove useful, but data are limited (Liang, 2016). Tetracyclines, including doxycycline, are efective but generally not recommended during pregnancy, because of the risk for fetal deciduous-teeth discoloration. All women with syphilis are ofered counseling and testing for HIV and other STDs. Following syphilis treatment, serological testing to detect treatment failures is done at 3 to 6 months and usually confirms a fourfold drop in VDRL or RPR titers. During pregnancy, serological titers can be checked monthly in women at high risk for reinfection (Workowski, 2015).


Obstentrics_Williams

Obstentrics_Williams. In some instances, a woman may present without symptoms but describes recent sexual contact with a person who has been diagnosed with syphilis. She should be evaluated clinically and serologically. If her partner is diagnosed and their sexual contact occurred within the preceding 90 days, the gravida is treated presumptively for early syphilis, even if serological test results are negative. his accounts for early infection but before seroconversion. If contact was earlier than 90 days ago, treatment is based on serological results (Workwoski, 2015). Women with a history of penicillin allergy should have either an oral stepwise penicillin-dose challenge or skin testing performed to confirm the risk of immunoglobulin E (IgE)mediated anaphylaxis. If conirmed, penicillin desensitization, shown in Table 65-2, is recommended and then followed by benzathine penicillin G treatment (Wendel, 1985). TABLE 65-2. Penicillin Allergy-Oral Desensitization


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Obstentrics_Williams. TABLE 65-2. Penicillin Allergy-Oral Desensitization Protocol for Patients with a Positive Skin Test Penicillin V Amountb Cumulative Dosea (units/mL) mL Units Dose (units) 1 1000 0.1 100 100 2 1000 0.2 200 300 3 ·1000 0.4 400 700 4 1000 O.S 800 1500 5 1000 1.6 1600 3100 6 1000 3.2 3200 6300 7 1000 6.4 6400 12,700 8 10,000 1.2 12,000 24,700 9 10,000 2.4 24,000 4S,700 10 10,000 4.S 4S,OOO 96,700 11 SO,OOO 1.0 80,000 176,700 12 80,000 2.0 160,000 336,700 13 SO,OOO 4.0 320,000 656,700 14 SO,OOO 8.0 640,000 1,296,700 alnterval between doses: 15 Elapsed time: 3 hours and 45 minutes. Cumulative dose: 1.3 million units. Observation period: 30 minutes before parenteral adminis tration of penicillin. bThe specific amount of drug was diluted in approximately 30 mL of water and administered orally. From Wendel, 1985, with permission.


Obstentrics_Williams

Obstentrics_Williams. Distinct from allergy, a Jarisch-Herxheimer reaction develops following penicillin treatment in most women with primary syphilis and approximately half with secondary infection. Uterine contractions, mild maternal temperature elevation, decreased fetal movement, and fetal heart rate decelerations are findings. Reaction treatment is supportive with antipyretics as needed, hydration, and oxygen supplementation (Klein, 1990). In a study of 50 gravidas who received benzathine penicillin for syphilis, Myles and associates (1998) reported a 40-percent incidence of Jarisch-Herxheimer reactions. Of the 31 women monitored electronically, 42 percent developed regular uterine contractions, and 39 percent developed variable decelerations. All contractions resolved within 24 hours of therapy. Accordingly, for fetuses of viable age, some recommend administering the irst dose of antibiotic in labor and delivery and with continuous fetal monitoring for at least 24 hours (Rae, 2017). Others recommend


Obstentrics_Williams

Obstentrics_Williams. for fetuses of viable age, some recommend administering the irst dose of antibiotic in labor and delivery and with continuous fetal monitoring for at least 24 hours (Rae, 2017). Others recommend this only if sonographic signs of fetal syphilis, described earlier, are found (Duf, 2014; Wendel, 2002). If this second plan is elected, patients are counseled on reaction signs and encouraged to seek evaluation if they develop.


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Obstentrics_Williams. Of notiiable STDs, infections caused by Neisseria gonorrhoeae are the second most common. The incidence of gonorrhea in the United States has continued to rise since 2009, and in 2015, the rate was 124 cases per 100,000 persons (Centers for Disease Control and Prevention, 2016c). he highest rates in women of any ethnicity were in those aged 15 to 24 years. In pregnant women, its prevalence approximates 0.6 percent (Blatt, 2012). In most pregnant women, infection is limited to the lower genital tract-the cervix, urethra, and periurethral and vestibular glands. Acute salpingitis is rare in pregnancy. But, pregnant women account for a disproportionate number of disseminated gonococcal infections (Bleich, 2012).


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Obstentrics_Williams. Gonococcal infection can have deleterious efects in any trimester. Untreated gonococcal cervicitis is associated with septic abortion as well as infection after voluntary abortion (Burkman, 1976). Preterm delivery, prematurely ruptured membranes, chorioamnionitis, and postpartum infection are more frequent in women with gonococcal infection (lger, 1988; Johnson, 2011). Vertical transmission of gonorrhea is predominantly due to fetal contact with vaginal infection during birth. he predominant sequela is gonococcal ophthalmia neonatorum, which can lead to corneal scarring, ocular perforation, and blindness. Transmission rates are high and approximate 40 percent (Laga, 1986). Accordingly, as discussed in Chapter 32 (p. 613), ocular prophylaxis is provided to newborns (Mabry-Hernandez, 2010).


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Obstentrics_Williams. Pregnant women who live in high-prevalence areas or who are at risk for gonorrhea should undergo irst-trimester screening. Risk factors include age �25 years; prior gonococcal infection; other STDs; prostitution; new or multiple sexual partners; drug abuse; black, Hispanic, or American Indian or laska Native ethnicity; and inconsistent condom use (American Academy of Pediatrics, 2017). For women who test positive, screening for syphilis, chlamydial infection, and HIV should precede treatment, if possible. Gonococcal infection is a marker for concomitant chlamydial infection. Thus, if chlamydial testing is unavailable, presumptive chlamydial therapy is given to women treated for gonorrhea.


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Obstentrics_Williams. Screening for gonorrhea in women is by culture or nucleic acid ampliication tests (NAATs). NAATs have replaced culture in most laboratories, and kits are available for specific collection from the vagina, en do cervix, or urine. Of these, vaginal or cervical samples are preferred, as urine collection may detect up to 10 percent fewer infections (Papp, 2014). If used, the initial urine stream, not midstream, is collected. NAATs are also recommended for diagnosis of rectal or pharyngeal disease, but participating laboratories must be CLIA (Clinical Laboratory Improvement Amendments) compliant with required test modifications. Culture is also available for these anatomical sites. Rapid POC tests for gonorrhea, although available, do not yet reach the sensitivity or specificity of culture or NAAT and have not been rigorously studied in pregnant women (Herbst de Cortina, 2016).


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Obstentrics_Williams. Gonorrhea treatment has evolved during the past decade due to the ability of N gonorrhoeae to rapidly develop antimicrobial resistance. The current treatment for uncomplicated gonococcal infection during pregnancy is 250 mg of cetriaxone intramuscularly plus 1 g of azithromycin orally (Workowski, 2015). he latter provides another drug with a diferent mechanism of action against N gonorrhoeae and treats chlamydial co-infections. Patients are instructed to abstain from sexual intercourse for 7 days ater they and their sexual partners have completed treatment. u an alternative regimen, a single, 400-mg oral dose of cefixime plus 1 g of azithromycin should be reserved for situations that preclude cetriaxone treatment. With cephalosporin allergy, a 240-mg intramuscular dose of gentamicin can be coupled with a 2-g oral azithromycin dose. Repeat testing is recommended in the third trimester for any woman treated for gonorrhea in the first trimester and for any uninfected woman who is at high


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Obstentrics_Williams. coupled with a 2-g oral azithromycin dose. Repeat testing is recommended in the third trimester for any woman treated for gonorrhea in the first trimester and for any uninfected woman who is at high risk for gonococcal infection (American Academy of Pediatrics, 2017).


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Obstentrics_Williams. Treatment is recommended for sexual contacts. Expedited therapy, discussed on page 1241, is a less-desirable option due to the now-preferred injectable regimen.


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Obstentrics_Williams. Gonococcal bacteremia may cause disseminated infections that manifest as petechial or pustular skin lesions, arthralgias, or septic arthritis. For treatment of septic arthritis, the CDC recommends ceftriaxone, 1 g intramuscularly or intravenously (IV) every 24 hours plus a single 1-g oral dose of azithromycin (Workowski, 2015). Treatment is continued for 24 to 48 hours ater clinical improvement, and therapy is then changed to an oral agent to complete 1 week of therapy. Prompt recognition and antimicrobial treatment will usually yield favorable outcomes in pregnancy (Bleich, 2012). Meningitis and endocarditis rarely complicate pregnancy, but they may be fatal (Bataskov, 1991; Burgis, 2006). For gonococcal endocarditis, ceftriaxone 1 to 2 g IV every 12 hours should be continued for at least 4 weeks, and for meningitis, 10 to 14 days. A single 1-g oral dose of azithromycin is also provided for chlamydial co-infection (Workowski, 2015).


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Obstentrics_Williams. Chlamydia trachomatis is an obligate intracellular bacterium that has several serotypes, including those that cause lymphogranuloma venereum. The most commonly encountered strains are those that attach only to columnar or transitional cell epithelium and cause cervical infection. It is the most common reportable STD in the United States, and the overall chlamydial infection rate among women was 646 cases per 100,000 females in 2015 (Centers for Disease Control and Prevention, 2016c). Most pregnant women have asymptomatic infection, but a third have urethral syndrome, urethritis, or Bartholin gland infection (Peipert, 2003). Mucopurulent cervicitis may be due to chlamydial or gonococcal infection or both. Other chlamydial infections not usually seen in pregnancy are endometritis, salpingitis, reactive arthritis, and Reiter syndrome.


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Obstentrics_Williams. The role of chlamydial infection in pregnancy complications remains controversial. A few studies have reported a direct association between C trachomatis and miscarriage, whereas most show no correlation (Baud, 2011; Coste, 1991; Paukku, 1999). It is disputed whether untreated cervical infection increases the risk of preterm delivery, preterm ruptured membranes, low birthweight, or perinatal mortality (Andrews, 2000, 2006; BIas, 2007; Johnson, 2011; Moodley, 2017; Silva, 2011). Chlamydial infection has not been associated with a greater risk of chorioamnionitis or with peripartum pelvic infection (Berman, 1987; Gibbs, 1987). However, delayed postpartum uterine infection has been described by Hoyme and associates (1986). The syndrome, which develops 2 to 3 weeks postpartum, is distinct from early postpartum metritis. It is characterized by vaginal bleeding or discharge, low-grade fever, and uterine tenderness.


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Obstentrics_Williams. Infection poses a higher risk to the newborn than to the mother. Vertical transmission leads to infection in 8 to 44 percent of neonates delivered vaginally from afected women (Rosenman, 2003). Of neonatal infections, conjunctivitis is the most common (Chap. 32, p. 613). Perinatal transmission to newborns can also cause pneumonia. Currently, the U.S. Preventive Services Task Force (LeFevre, 2014) as well as the American Academy of Pediatrics and American College of Obstetricians and Gynecologists (2017) recommend chlamydia screening for all women at the irst prenatal visit. he College further suggests testing in the third trimester for those treated in the irst trimester; all women aged ;25 years; and those aged �25 years with behavioral factors, which mirror those for women at risk for gonorrhea. In one review of repeat chlamydial infections among women, the reinfection rate was 14 percent, and most recurred within the first 8 to 10 months (Hosenfeld, 2009).


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Obstentrics_Williams. Diagnosis is made predominantly by culture or NAAT. Cultures are more expensive and less accurate than newer NAA T s (Greer, 2008). Of samples for NAAT, vaginal or cervical TABLE 65-3. Oral Treatment of Chlamydia trachomatis Infections During Pregnancy Erythromycin ethylsuccinate, 400 mg four times daily for 14 d Data from Workowski, 2015. samples are preferred, as urine collection may detect up to 10 infections (Papp, Wiesenfeld, 2017). Roberts and associates (2011) evaluated NAA T of urine speci mens compared with cervical secretions in more than 2000 pregnant women and found them to be equivalent. As with gonorrhea, the irst portion of the urine stream is collected.


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Obstentrics_Williams. Currently recommended treatment regimens for chlamydial infections are shown in Table 65-3. Azithromycin is irst-line treatment and is safe and efective in pregnancy. The luoroquinolones and doxycycline are usually avoided in pregnancy, and erythromycin estolate is contraindicated because of drug-related hepatotoxicity. Chlamydial testing is repeated 3 to 4 weeks after therapy completion and ,gain 3 months after treatment. In high-risk individuals, third-trimester rescreening is recommended (Workowski, 2015).


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Obstentrics_Williams. To prevent STD transmission, guidelines for expedited partner therapy (EPT) have been created by the Centers for Disease Control and Prevention (2006a) and are endorsed by the American College of Obstetricians and Gynecologists (2015). With EPT, a prescription is provided to the diagnosed patient for their partner. It is delivered by the patient to their partner without medical assessment of the partner or professional counseling. EPT ideally does not replace traditional strategies, such as standard patient referral with screening for other STDs. EPT is acceptable for treatment of sexual contacts with chlamydial infection. In light of new guidelines that recommend injectable ceftriaxone, EPT for gonorrhea is less desirable unless the partner will otherwise not seek treatment (Centers for Disease Control and Prevention, 2016a). Fewer data are available to assess this strategy for trichomoniasis (Kissinger, 2006; Schwebke, 2010). EPT is not recommended for syphilis (Workowski,r2015).


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Obstentrics_Williams. Although sanctioned by the CDC, EPT is not legal in several states. \{oreover, the risk of litigation in the event of adverse outcomes may be elevated when a practice has uncertain legal status or is outside formally accepted community practice standards (Centers for Disease Control and Prevention, 2006a). The legal status of EPT in each of the 50 states can be found at: http://ww.cdc.gov/std/ept/legal!default.htm.


Obstentrics_Williams

Obstentrics_Williams. L], L2, and L3 serovars of C trachomatis cause ymphogranuloma venereum (LG). he primary genital infection is transient, is seldom recognized, and is not linked with vertical transmission to the fetus. It can be confused with chancroid. Classically, matted inguinal adenitis may develop on either side of the inguinal ligament to give rise to the "groove sign." At times, these nodes may suppurate. Ultimately, the lymphatics of the lower genital tract and perirectal tissues may be involved. Here, sclerosis and fibrosis can cause vulvar elephantiasis and severe rectal stricture. Fistula formation involving the rectum, perineum, and vulva may also evolve. For treatment during pregnancy, erythromycin base, 500 mg orally four times daily, is given for 21 days (Workowski, 2015). Some authorities instead use szithromycin, 1 g orally weekly for 21 days, although data regarding eicacy are scarce.


Obstentrics_Williams

Obstentrics_Williams. his virus poses a disproportionately higher risk to the newborn than to the mother. hus, strategies in pregnancy aim to curb rates of vertical transmission.


Obstentrics_Williams

Obstentrics_Williams. Two types of herpes simplex viruses are distinguished based on immunological diferences. Yet, the two viruses have signiicant DNA sequence homology, and thereby, prior infection with one type attenuates a primary infection with the other. Type 2 HSV is recovered almost exclusively from the genital tract and is usually transmitted by sexual contact. Type 1 is responsible for most nongenital infections and typically is acquired in childhood. However, more than half of new cases of genital herpes in adolescents and young adults are now caused by HSV-1 infection (Bernstein, 2013). his rise in the prevalence of HSV-1 genital disease is thought to stem from an increase in oral-genital sexual practices. Another explanation is that HSV-1 acquisition has declined in childhood as a result of improved living conditions and hygiene (Bradley, 2014; Xu, 2007). Without prior exposure, this renders young people without HSV-l antibodies susceptible to genital acquisition of HSV-l or -2.


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Obstentrics_Williams. Genital herpes simplex virus afects an estimated 50 million adolescents and adults (Workowski, 2015). Most women are unaware of their infection, but HSV-2 seroprevalence among non-Hispanic white females in the United States was 15.3 from 2007 to 2010 and among black females, it was 53 percent (Fanfair, 2014; Schulte, 2014). In one study of nearly 16,000 pregnant women from 2000 to 2010, the overall seroprevalence of HSV-2 was 16 percent, and for HSV-l, it was 66 percent (Delaney, 2014). Seronegative pregnant women have a 4 to 5 percent risk to acquire HSV-l or -2 during pregnancy (Brown, 1997; Kulhanjian, 1992). For those who are HSV-l seropositive, acquisition risk for HSV-2 approximates 2 percent (Brown, 1997).


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Obstentrics_Williams. Once transmitted by contact, HSV-l or -2 replicates at the entry site. Following mucocutaneous infection, the virus moves retrograde along sensory nerves. It then remains latent in cranial nerves or dorsal spinal ganglia, but recurrences are common. HSV infections may be categorized into three groups.


Obstentrics_Williams

Obstentrics_Williams. First episode primary inection describes the case in which HSV-l or 2 is isolated from a lesion in the absence of HSV-l or -2 serological antibodies. The typical incubation period of 6 to 8 days (range 1 to 26 days) may be followed by a papular eruption with itching or tingling, which then becomes painful and vesicular. Multiple vulvar and perineal lesions mayror may not coalesce, and then ulcerate (Fig. 65-5). Associated inguinal adenopathy can be severe. Many women do not present with typical lesions. Instead, a pruritic or painful abraded area or knife-cut may be found. Cervical involvement is common, although it may be inapparent clinically. Transient systemic influenza-like symptoms are frequent and are presumably caused by viremia. Some cases are severe enough to require hospitalization. Hepatitis, encephalitis, or pneumonia infrequently develop, and disseminated disease is rare. After 2 to 4 weeks, all signs and symptoms of infection disappear. Instead of these classic


Obstentrics_Williams

Obstentrics_Williams. Hepatitis, encephalitis, or pneumonia infrequently develop, and disseminated disease is rare. After 2 to 4 weeks, all signs and symptoms of infection disappear. Instead of these classic symptoms, the percentage of asymptomatic primary HSV-2 genital infections may be as high as 90 percent (Fanfair, 2013).


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Obstentrics_Williams. FIGURE 65-5 First-episode primary genital herpes simplex virus infection. Vesicles and knife-cut lesions are indicated by arrows. Small ulcers rim the anus. Similar lesions can typically be seen on the vulva. First episode nonprimay inection is diagnosed when one HSV type is isolated from a lesion in a woman who has only the other serological HSV-type antibody present. In general, compared with primary infection, nonprimary infections are characterized by fewer lesions, less pain, fewer systemic manifestations, and briefer duration of lesions and viral shedding. This is likely because of some immunity from cross-reacting antibodies, for example, from childhood-acquired HSV-l infection.


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Obstentrics_Williams. Recurrent disease is characterized by isolation of HSV-l or -2 from the genital tract in women with the same serotype antibodies. During the latency period, in which viral particles reside in nerve ganglia, reactivation is common and mediated through poorly understood stimuli. The resulting lesions generally are fewer in number, are less tender, and shed virus for a shorter period than those of primary infection. Typically, they recur at the same sites. Genital disease recurrences are more frequently caused by HSV-2 compared with HSV-l. Recurrences are most frequent in the irst year after initial infection, and rates slowly decline subsequently (Benedetti, 1999). Gravidas with a known prior history of genital HSV often experience recurrences (Sheield, 2006).


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Obstentrics_Williams. Asymptomatic viral shedding is defined by the absence of clinical findings. Most infected women shed virus intermittently over time, and most HSV transmission to a partner occurs during these periods of asymptomatic viral shedding. he virus can be passed to the fetus/neonate by three routes: peripartum in 85 percent, (2) postnatal in 10 percent, or intrauterine in 5 percent Qames, 2015). As discussed in Chapter 18 (p. 347), evidence does not suggest an obvious link between HSV infection and miscarriage (Zhou, 2015).


Obstentrics_Williams

Obstentrics_Williams. Peripartum transmission is by far the more frequent route of infection, and the fetus is exposed to virus shed from the cervix or lower genital tract. HSV-l or -2 invades the uterus following membrane rupture or is transmitted by contact at delivery. The newborn is mainly infected, but rare cases of maternal endometritis have .been described (Hollier, 1997; McGill, 2012). Neonatal manifestations vary. First, infection may be localized to the skin, eye, or mouth-SEM disease-in approximately 40 percent of cases. Second, central nervous system disease with encephalitis is seen in 30 percent. Last, disseminated disease with involvement of multiple major organs is found in 32 percent. Localized infection is usually associated with a good outcome. Conversely, even with acyclovir treatment, disseminated infection has a mortality rate of nearly 30 percent (Corey, 2009; Kimberlin, 2011). Of disseminated or cerebral infection survivors, serious developmental and central nervous system morbidity


Obstentrics_Williams

Obstentrics_Williams. infection has a mortality rate of nearly 30 percent (Corey, 2009; Kimberlin, 2011). Of disseminated or cerebral infection survivors, serious developmental and central nervous system morbidity is seen in 20 to 50 percent.


Obstentrics_Williams

Obstentrics_Williams. The neonatal infection rate is 0.5 to 1 per 10,000 births in the United States (Flagg, 2011; Mahnert, 2007). Most infected newborns are born to mothers with no reported history ofHSV infection (Gardella, 2010). The risk of neonatal infection cor relates with the presence of HSV in the genital tract, the HSV type, invasive obstetrical procedures, and stage of maternal infection (Brown, 2005, 2007). For example, neonates born to women who acquire genital HSV near the time of delivery have a 30-to 50-percent risk of infection. This is attributed to higher viral loads and the lack of transplacental protective antibodies (Brown, 1997,r2000). Women with recurrent HSV have less than a I-percent risk of neonatal infection (Pasternak, 2010; Prober, 1987). Postpartum transmission is uncommon and passed to the newborn by contact with an infected mother, family member, or health-care worker. The clinical presentation mirrors that with peripartum transmission.


Obstentrics_Williams

Obstentrics_Williams. In utero transmission ofHSV-l or HSV-2 is rare and is part of the TORCH (roxoplasmosis, Qther, rubella, �ytomegalovi rus, herpes virus) collection of infections. Intrauterine HSV infection classically leads to disease involving the skin (blisters, scarring), the central nervous system (hydranencephaly, micro cephaly, intracranial calcification), or the eyes (chorioretini tis, microphthalmia) (Hutto, 1987). Bone and viscera can be involved (Marquez, 2011). If seen sonographically, indings should prompt viral serological testing as described next. PCR analysis of an amniocentesis sample is another potential tool (Diguet, 2006). Several organizations recommend against routine serological HSV screening in asymptomatic gravidas (American College of Obstetricians and Gynecologists, 20 16b; Workowski, 2015;


Obstentrics_Williams

Obstentrics_Williams. Several organizations recommend against routine serological HSV screening in asymptomatic gravidas (American College of Obstetricians and Gynecologists, 20 16b; Workowski, 2015; U.S. Preventive Services Task Force, 2016). However, for those with a clinically suspicious lesion, a diagnosis should be conirmed by laboratory testing. Available HSV tests are either virological or type-speciic serological tests.


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Obstentrics_Williams. Direct virological tests are can be performed on a specimen from the mucocutaneous lesion. PCR or culture of the sample is a testing option. Of the two, PCR assays are more sensitive, the results generally are available in 1 to 2 days, and specimen handling is easier. In contrast, for viral culture, the sensitivity of HSV isolation is relatively low as vesicular lesions ulcerate and then crust. Also, results sometimes are not available for 7 to 14 days (Strick, 2006). Regardless of the test performed, HSV viral types should be diferentiated (LeGof, 2014). Importantly, a negative culture or PCR result does not exclude infection. In contrast, false-positive results are rare.


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Obstentrics_Williams. Serological assays are available to detect antibodies produced against speciic HSV glycoproteins, Glrand G2. These proteins evoke type-speciic antibody responses to HSV-l and HSV-2 infection, respectively, and they reliably diferentiate the two. IgG antibodies develop 1 to 2 weeks after a primary infection and then persist. This permits conirmation of clinical infection and identiication of asymptomatic carriers. Providers should request type-speciic glycoprotein G-based assays when serology is being performed. Sensitivity approaches 90 to 100 percent, and speciicity is 99 to 100 percent (Wald, 2002). IgM antibody detection is not a useful test.


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Obstentrics_Williams. In nonpregnant patients, antiviral therapy with acyclovir, vala cyclovir, or famciclovir is used to treat irst-episode genital herpes. Oral or parenteral preparations attenuate clinical infec tion and viral shedding duration. Suppressive therapy is also an option to limit recurrent infections and to reduce heterosexual transmission (Corey, 2004). In pregnant women, acyclovir is safe (Briggs, 2015). Through 1999, the manufacturers of acyclovir and valacyclovir maintained a registry of outcomes following exposure to these drugs during pregnancy. More than 700 neonates exposed dur ing the irst trimester were evaluated, and there were no adverse efects attributable to acyclovir (Stone, 2004). At this time, data are insuicient regarding famciclovir exposure, although a pregnancy registry is being maintained (1-888-669-6682).


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Obstentrics_Williams. For a primary outbreak during pregnancy, women may be given antiviral therapy to attenuate and decrease the duration of symptoms and viral shedding (Table 65-4). Women with HIV co-infection may require a longer duration of treatment. Those with severe or disseminated HSV are given IV acyclovir, 5 to 10 mg/kg every 8 hours for 2 to 7 days until clinically improved. This is followed by oral antiviral drugs to complete at least 10 days of total therapy (W orkowski, 2015). For intense discomfort, oral analgesics and topical anesthetics may provide some relief, and comorbid urinary retention is treated with an indwelling bladder catheter. For recurrent HSV infections during pregnancy, antiviral treatment is provided mainly for symptom relief (see Table 65-4) . Although uncommon, acyclovir resistance has been reported, predominantly with HSV-2 and in immunocompromised patients (Andrei,r2013).


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Obstentrics_Williams. During pregnancy, amniocentesis, percutaneous cord blood sampling, or transabdominal chorionic villus sampling may be performed even with active genital lesions. With active lesions, however, internal electronic monitoring during labor is not recommended. T ranscervical procedures may best be delayed until lesions have resolved (American College of Obstetricians and Gynecologists, 20 16b).


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Obstentrics_Williams. To diminish vertical transmission risks, cesarean delivery is indicated for women with active genital lesions or prodromal symptoms (American College of Obstetricians and Gynecologists, 20 16b). Several studies have shown that acyclovir or valacyclovir suppression initiated at 36 weeks' gestation for gravidas with recurrences during pregnancy lowers the number of HSV outbreaks at term. The goal is to decrease the need for cesarean delivery (Hollier, 2008). his suppressive therapy will also decrease viral shedding (Scott, 2002; Sheield, 2006; Watts, 2003). One systematic review evaluated acyclovir prophylaxis given from 36 weeks to delivery to women with HSV recurrence during pregnancy. Sheield and colleagues (2003) found that suppressive therapy was associated with signiicantly lower rates of clinical HSV recurrence, cesarean deliveries for HSV recurrences, total HSV detection, and asymptomatic shedding. Subsequent studies using valacyclovir suppression have shown similar results


Obstentrics_Williams

Obstentrics_Williams. rates of clinical HSV recurrence, cesarean deliveries for HSV recurrences, total HSV detection, and asymptomatic shedding. Subsequent studies using valacyclovir suppression have shown similar results (Andrews, 2006; Sheield, 2006). Because of these studies, the


Obstentrics_Williams

Obstentrics_Williams. TABLE 65-4. Oral Antiviral Medications for Herpesvirus Infection in Pregnancya Acyclovir, 400 mg three times daily for 7-10 d Valacyclovir, 1 9 twice daily for 7-1r0 days Acyclovir, 400 mg three times daily for 5 days Acyclovir, 800 mg twice daily for 5 days Acyclovir, 800 mg three times daily for 2 d Valacyclovir, 500 mg twice daily for 3 days Valacyclovir, 1 9 once daily for 5 days Acyclovir,r400 mg three times daily from 36 weeks until delivery Valacyclovir, 500 mg twice daily from 36 weeks until delivery Famciclovir not preferred during pregnancy due to fewer safety data. Data from Workowski, 2015.


Obstentrics_Williams

Obstentrics_Williams. Valacyclovir, 500 mg twice daily from 36 weeks until delivery Famciclovir not preferred during pregnancy due to fewer safety data. Data from Workowski, 2015. American College of Obstetricians and Gynecologists (2016b) recommends viral therapy at or beyond 36 weeks for women who had primary genital herpes infection or active recurrent genital herpes during pregnancy. It is unclear whether suppression is needed for women with outbreaks before but not during pregnancy. Notably, despite maternal antiviral suppression, several cases of atypical neonatal herpes infection have been reported (Pinninti, 2012).


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Obstentrics_Williams. On presentation for delivery, a woman with a history of HSV should be questioned regarding prodromal symptoms such as vulvar burning or itching. A careful examination of the vulva, vagina, and cervix is performed, and women without genitalrlesions may proceed with labor and delivery. Use of a fetal scalp electrode can raise the transmission risk. But, electrode placement is reasonable if needed in the absence of active lesions (American College of Obstetricians and Gynecologists, 2016b). Suspicious lesions should be cultured or PCR tested. Cesarean delivery is indicated for women with genital lesions or prodromal symptoms. It is not recommended for women with a history of HSV infection but no active genital disease at the time of delivery. Moreover, an active lesion in a nongenital area is not an indication for cesarean delivery. Instead, an occlusive dressing is placed, and vaginal delivery is allowed.


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Obstentrics_Williams. With preterm ruptured membranes, no evidence suggests that external lesions cause ascending fetal infection. Major and associates (2003) described expectant management of preterm premature membrane rupture in 29 women at gestational ages <31 weeks. There were no cases of neonatal HSV, and the maximum infection risk was calculated to be 10 percent. Antiviral treatment is recommended. For women with a clinical recurrence at delivery, there is not an absolute duration of membrane rupture beyond which the fetus would not beneit from cesarean delivery (merican College of Obstetricians and Gynecologists, 2016d).


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Obstentrics_Williams. Women with active HSV may breastfeed if there are no active breast lesions. Strict hand washing is essential. Val acyclovir and acyclovir may be used for symptomatic maternal lesions during breastfeeding, as drug concentrations in breast milk are low. One study found the acyclovir concentration to be only 2 percent of that used for therapeutic dosing of the neonate (Sheield, 2002a).


Obstentrics_Williams

Obstentrics_Williams. Haemophilus ducryi can cause painul, nonindurated genital ulcers termed sot chancres. At times, these are accompanied by painul suppurative inguinal lymphadenopathy. Although common in some developing countries, only 11 cases were reported in the United States in 2015 (Centers for Disease Control and Prevention, 20 16c). Appropriate media are not widely accessible, and no Food and Drug Administration (FDA)-cleared PCR test is yet available. Instead, painul genital ulcer(s) and negative screening for syphilis or HSV leads to a presumptive diagnosis. Treatment in pregnancy is azithromycin, 1 g orally as a single dose; erythromycin base, 500 mg orally three times daily for 7 days; or cetriaxone, 250 mg in a single intramuscular dose (Workowski, 2015).


Obstentrics_Williams

Obstentrics_Williams. This is a common STD, and more than 40 types infect the genital tract. In the United States from 2005 to 2006, the overall HPV prevalence was 40 percent in females aged 14 to 59 years (Liu, 2016). Prevalence is highest in younger women, and some of this seroprevalence now relects HPV vaccination in this age group (Brouwer, 2015). Most reproductive-aged women become infected within a few years of becoming sexually active, and most infections are asymptomatic and transient. High-risk types are those with the most oncogenic potential. Of these, HPV types 16 and 18 are oten associated with dysplasia (Chap. 63, p. 1193). Mucocutaneous external genital warts termed condyloma acuminata are usually caused by types 6 and 11r.


Obstentrics_Williams

Obstentrics_Williams. For unknown reasons, genital warts frequently increase in number and size during pregnancy. hese lesions may sometimes grow to fill the vagina or cover the perineum, thus making vaginal delivery or episiotomy diicult. Maternal HPV infection does not appear to be related to preterm labor (Subramaniam, 2016). Genital wart eradication during pregnancy is usually not neces sary unless they are symptomatic. herapy is directed toward ity to the mother and fetus. Several agents are available, but no deinitive evidence supports superiority of one over another (Workowski, 2015). Response to treatment during pregnancy may be incomplete, but lesions frequently improve or regress rapidly following delivery. Trichloroacetic or bichloracetic acid, 80-to 90-percent solu tion, applied topically weekly, is an efective regimen for external warts. Some prefer cyotherapy, laser ablation, or surgical excision.


Obstentrics_Williams

Obstentrics_Williams. Trichloroacetic or bichloracetic acid, 80-to 90-percent solu tion, applied topically weekly, is an efective regimen for external warts. Some prefer cyotherapy, laser ablation, or surgical excision. Agents not recommended in pregnancy because of concerns for maternal and fetal safety include podophyllin resin, podoilox solution or gel, imiquimod cream, and sinecatechins. There are three vaccines available for long-term prevention.


Obstentrics_Williams

Obstentrics_Williams. Gardasil (HPV 4) is a quadrivalent vaccine against HPV types 6,11, 16, and 18. his is being replaced by Gardasil9 (HPV9), a nonavalent vaccine that protects against all the types in HPV 4 plus types 31,r33,r45, 52, and 58. Cervarix (HPV2) is a bivalent vaccine against HPVs 16 and 18. One of these vaccines is selected and given as a three-dose series on a schedule of 0, 1-2, and 6 months for those aged 15 to 26 years. A two-dose regimen, given at 0 and again at 6 to 12 months, is now recommended for girls aged 9 to 14 years (Meites, 2016). Vaccines are licensed for females aged 9 to 26 years, and the target age is 11 to 12 years. he vaccines are not recommended for pregnant women, however, inadvertent exposures do occur. No adverse pregnancy outcomes are associated with the vaccines (Moreira, 2016; Panagiotou, 2015; Vichnin, 2015). If a woman is found to be pregnant after starting the vaccination series, the remaining doses are delayed and given after delivery (American College of


Obstentrics_Williams

Obstentrics_Williams. 2016; Panagiotou, 2015; Vichnin, 2015). If a woman is found to be pregnant after starting the vaccination series, the remaining doses are delayed and given after delivery (American College of Obstetricians and Gynecologists, 2017a). Women who are breastfeeding may receive the vaccine.


Obstentrics_Williams

Obstentrics_Williams. Vertical transmission rates ofHPV to the newborn are minimal. Juvenile-onset recurrent respiratory papillomatosis QoRRP) is a rare, benign neoplasm of the larynx. It can cause hoarseness and respiratory distress in children and is most often caused by HPV 6 or 11. Risks for infection are maternal genital HPV infection and longer labors (Niyibizi, 2014). Many newborns are likely exposed to HPV, but few develop JoRRP (Silverberg, 2003; Smith, 2004; Tenti, 1999). For example, the national incidence of JoRRP in 2006 in the United States ranged from 0.5 to 1 per 100,000 children (Marsico, 2014). The beneit of cesarean delivery to decrease transmission risk is unknown, and thus it is currently not recommended solely to prevent HPV transmission (Workowski, 2015). HPV vaccination may ultimately decrease JoRRP rates in the uture (Matys, 2012).


Obstentrics_Williams

Obstentrics_Williams. Pregnant women frequently develop increased vaginal discharge. his may be a physiological discharge, described in Chapter 4 (p. 51), but should be diferentiated from symptomatic vaginitis, which is also common in pregnancy. Fortunately, vaginitis is prevented in part by normal vaginal lora. To better understand this, studies of the composition and function of the normal vaginal microflora are currently underway with the Vaginal Human Microbiome Project (Huang, 2014). Not an infection in the ordinary sense, bacterial vaginosis (BY) is a maldistribution of normal vaginal flora. With BV, num bers of lactobacilli are decreased, and anaerobic bacteria spe cies are overrepresented. hese anaerobes include Gardnerela, Prevotela, Mobiluncus, and Bacteroides species; Atopobium vagi nae; and BV-associated bacteria, provisionally named BVAB 1, BVAB2, and BVAB3. hese last three are newly recognized bacteria found in women with BV (Fredricks, 2005).


Obstentrics_Williams

Obstentrics_Williams. BVAB2, and BVAB3. hese last three are newly recognized bacteria found in women with BV (Fredricks, 2005). Molecular ribosomal RNA gene sequencing techniques have greatly aided this understanding of the vaginal lora, also called the vaginal m icro biota. Five types of vaginal microbiota exist, referred to as communiy state ypes (eSTs). And, a woman can be categorized to one of these ive CSTs based on her vaginal microbiota composition (Ravel, 2011). Researchers have begun to quantiy the risk of BV by these CST groups. Speciically, CST s I, II, III, and V are rich in lactobacilli. In contrast, CST IV is a heterogeneous microbiota of strict anaerobes and is associated with BV. CSTs vary racially, and CST IV is also the most common in asymptomatic, healthy black women (Fettweis, 2014). Pregnancy-related changes in vaginal micro biota are also being defined and may hold keys to adverse BV-related pregnancy outcomes, discussed subsequently (Romero, 2014).


Obstentrics_Williams

Obstentrics_Williams. Of childbearing-aged women in the United States, nearly 30 percent have BV. In black women, the prevalence approximates 50 percent (llsworth, 2007). Most women are asymptomatic, but a foul, thin vaginal discharge is a typical complaint. Associated risk factors are douching, multiple partners, smoking, and altered host immunity (Desseauve, 2012; Koumans, 2007; Murphy, 2016) .


Obstentrics_Williams

Obstentrics_Williams. For clinical diagnosis of BV, three of the four following criteria are present: (1) vaginal pH >4.5; (2) a thin, milky, noninlammatory vaginal discharge; (3) > 20 percent clue cells seen microscopically; and (4) a fishy odor ater addition of 10-percent potassium hydroxide to vaginal secretion samples (Amsel, 1983). The last is described as a positive "whif test." Likewise, alkalinity of seminal fluid and blood are responsible for foul-odor complaints ater intercourse and with menses in afected women. Clue cells are vaginal epithelial cells containing many attached bacteria, which create a poorly deined stippled cellular border (Fig. 65-6). he higher vaginal pH stems from diminished acid production by lactobacilli. Similarly, Trichomonas vaginalis infection is also associated with anaerobic overgrowth and resultant elaborated amines. hus, women diagnosed with BV should have no microscopic evidence of trichomoniasis (see Fig. 65-6).