Sage Journals: Discover world-class research

Abstract

Sexually transmitted infections (STIs) constitute a major public health problem in the UK and may result in very costly complications. Many STIs pose the risk of a number of adverse pregnancy outcomes including miscarriage, still birth, preterm delivery, low birth weight and ophthalmia neonatorum. National guidelines for the management of STIs are produced and regularly revised by the British Association of Sexual Heath and HIV. This review outlines the latest recommended treatment options during pregnancy for the commonly encountered STIs.

Keywords

pregnant women sexually transmitted infections treatment guidelines

Sexually transmitted infections (STIs) constitute a major public health problem, not only in the UK but worldwide. A 2003 House of Commons Health Select Committee inquiry into sexual health described a sexual health crisis in the UK that amounted to a public health emergency [1].

The number of newly diagnosed STIs in England remained high at 418,598 cases between 2008 and 2010 [101]. Many STIs pose the risk of a number of adverse pregnancy outcomes including miscarriage, still birth, preterm delivery, low birth weight and ophthalmia neonatorum. Effective management is imperative as STIs can be detrimental to both the mother and baby and can result in very costly complications.

Drugs selected for treatment should not be contraindicated in pregnant women, should have a high efficacy and be well tolerated.

The common STIs that are known to have significant implications in pregnancy are Chlamydia trachomatis, Neisseria gonorrhoeae, human papilloma virus (HPV), herpes simplex virus (HSV), Trichomonas vaginalis and syphilis. This review outlines the treatment options during pregnancy for the commonly encountered STIs. NICE has produced guidance for the routine antenatal care of healthy pregnant women, which includes specific recommendations for STI screening [102]. National guidelines for the management of STIs are produced and regularly revised by the British Association of Sexual Heath and HIV (BASHH) [103]. Readers are encouraged to review both NICE and BASHH guidelines for more comprehensive information.

It is beyond the remit of this article to discuss the management of HIV and hepatitis B during pregnancy.

Bacterial infections

C. trachomatis

C. trachomatis is an obligate intracellular bacterium of which there are several serotypes. It is the most common bacterial STI in the UK, with the highest rates in patients under 25 years of age. Furthermore, results from the National Chlamydia Screening Programme demonstrated a high level of asymptomatic infection [101]. Complications in women include pelvic inflammatory disease, ectopic pregnancy and infertility. Chlamydia, like other acute bacterial and viral STIs, is associated with increased risk of both HIV transmission and acquisition [2].

Untreated cervical chlamydia during pregnancy is associated with an increased risk of preterm delivery and premature rupture of membranes [3]. Mother-to-child transmission occurs at the time of vaginal birth and may result in ophthalmia neonatorum and pneumonitis in the infant and postpartum endometritis in the mother.

Nucleic acid amplification testing is the gold standard diagnostic method and offers high sensitivity (90–95%) and specificity. Endocervical or vaginal swabs are the specimens of choice and are of equivalent sensitivity.

Treatment of chlamydia during pregnancy

Erythromycin is safe for use in pregnancy but has a significant side-effect profile and is less efficacious (<95%) than azithromycin. The WHO recommends the use of azithromycin in pregnancy. The British National Formulary recommends the use of azithromycin in pregnant women only if no alternative is available, although the data that are available support its safety. When compared with erythromycin, meta-analysis showed amoxycillin to have a similar cure rate and a better side-effect profile [4]. However, penicillin has been shown to induce chlamydial latency in vitro. Tetracyclines are contraindicated in pregnancy because of the risk of bone and dental abnormalities in the infant.

Recommended regimens for chlamydia during pregnancy can be found in Box 1.

Contact tracing of sexual partners must be pursued and patients should be advised to avoid any — including condom protected — sexual intercourse for at least 7 days after both the patient and their sexual partner(s) have completed treatment. A repeat swab for test of cure is recommended for all pregnant women 6 weeks after treatment [102]. It is the authors' practice to rescreen in the third trimester.

Gonorrhea

Gonorrhea is caused by the Gram-negative diplococcus N. gonorrhoeae. It is the second most common bacterial STI in the UK [101]. Up to 50% of women may be asymptomatic and may not present until complications such as pelvic inflammatory disease are present [5]. Gonorrhea is associated with serious sequelae such as infertility, ectopic pregnancy, chronic pelvic pain and disseminated gonococcal infection.

Preterm delivery, premature rupture of membranes, chorioamnionitis and postpartum infection are more common in pregnant women with untreated gonorrhea [6]. Gonorrhea is transmitted to the newborn from the mothers' genital tract during birth and can cause ophthalmia neonatorum and systemic neonatal infection.

Diagnosis is often made using nucleic acid amplification testing. These are highly sensitive tests (>96%) [7,8]. Endocervical and vaginal swabs are of equivalent sensitivity [9]. False positives may occur, however. Confirmatory culture for gonococcus is essential to allow antimicrobial sensitivity testing, which is of paramount importance given increasing antibiotic resistance.

Box 1.

Recommended regimens for chlamydia during pregnancy.

Azithromycin 1 g oral single dose (recommended by WHO)

Erythromycin 500 mg p.o. for 7 days

Erythromycin 500 mg p.o. for 14 days

Amoxycillin 500 mg p.o. for 7 days

Treatment of gonorrhea during pregnancy

There is growing concern regarding the resistance and decreasing sensitivity of the gonococcus to many classes of antibiotics. Patients with gonorrhea frequently have concomitant infection with chlamydia. Intramuscular (im.) ceftriaxone plus cotreatment with azithromycin is now the first-line recommended treatment. Azithromycin is recommended as cotreatment irrespective of the results of chlamydia testing in order to prevent the emergence of cephalosporin resistance [10]. There is evidence to suggest synergy between azithromycin and cephalosporins [11]. Furthermore, pharyngeal gonorrhea may be more effectively eradicated with azithromycin cotreatment [12].

Oral cefixime plus cotreatment with azithromycin is an alternative to im. ceftriaxone. In 2010, 6.3% of gonococcal isolates demonstrated decreased susceptibility to cefixime and in 2009, 0.3% to ceftriaxone [101]. A total of 35.7% of isolates were resistant to ciprofloxacin in 2010 [101]. Moreover, quinolones are contraindicated in pregnancy.

Recommended regimens for gonorrhea during pregnancy can be found in Box 2.

Partner notification must be pursued and patients are advised to abstain from sexual intercourse until they and their partners have been successfully treated. A test of cure is recommended 1 week after treatment in all cases in view of concerns regarding emerging resistance. It is the authors' practice to advise repeat screening in the third trimester.

Syphilis

Syphilis is caused by the spirochete Treponema pallidum. The incubation period of primary syphilis is 9–90 days. The primary ulcer (chancre) usually occurs at the site of inoculation, which is usually the genital or perianal area. The lesion is classically solitary and painless but can be multiple and painful. The primary chancre spontaneously resolves after a few weeks and may go unnoticed. Secondary syphilis develops 4–8 weeks later. It has a wide variety of presentations and may mimic many other diseases and may be easily misdiagnosed as glandular fever or another similar viral illness. Clinical features of secondary syphilis include rash, lymphad-enopathy, mouth ulcers, fever and malaise. The symptoms and signs resolve without treatment. Long-term complications of untreated syphilis are neurological disease, cardiovascular disease and gummata (granulomatous skin lesions).

Box 2.

Recommended regimens for gonorrhea during pregnancy.

Ceftriaxone 500 mg im. injection plus azithromycin 1 g single oral dose

Cefixime 400 mg single oral dose plus azithromycin 1 g single oral dose (in those who refuse im. injection)

Spectinomycin 2 g im. single dose plus azithromycin 1 g single oral dose (in those who are allergic to penicillin or β-lactam)

There has been a marked increase in the number of cases of early syphilis observed since the late 1990s. There were a total of 2318 cases of early infectious syphilis diagnosed in England in 2010, albeit predominantly in men who have sex with men [101]. However, antepartum syphilis can have devastating consequences, resulting in preterm labor, polyhydramnios, hydrops, fetal death and congenital syphilis. Syphilis may be transmitted to the baby via the transplacental route at any stage of pregnancy.

In view of the potential profound adverse effects of syphilis during pregnancy it is recommended that all pregnant women in the UK are screened for syphilis at the initial antenatal appointment. Repeat serological testing may be indicated in women at high risk of syphilis, for example, those with sexual partners from high-risk groups or commercial sex workers.

Diagnosis and staging of disease is based on history, clinical examination and serology. Serology involves treponemal-specific tests and nontreponemal tests. Treponemal-specific tests include treponemal enzyme immunoassay to detect IgG and IgM and T. pallidum particle agglutination. These tests are specific for T. pallidum and are reported as positive or negative.

The nontreponemal tests include the Venereal Disease Research Laboratory test and rapid plasma reagin. Nontreponemal test titers usually correlate with disease activity. False positives can occur in many conditions including pregnancy.

Treatment of syphilis during pregnancy

The clinical management of syphilis should be lead by a genitourinary medicine clinician. All patients diagnosed with syphilis should have their HIV test repeated. Treatment of syphilis in pregnancy should be with parenteral penicillin appropriate for the stage of syphilis. Pregnant women with early-stage syphilis and higher Venereal Disease Research Laboratory test result have a higher risk of having an infant with congenital syphilis after adequate treatment of maternal syphilis [13,14]. Treatment in the last trimester is also associated with increased likelihood of congenital infection [13 –16]. Parenteral penicillin is the drug of choice as there are higher failure rates with nonpenicillin alternatives. Nonpenicillin alternatives include ceftriaxone, erythromycin and azithromycin. Penicillin desensitization should be considered in those patients reporting penicillin allergy [17].

The Jarisch—Herxheimer reaction may occur just as for nonpregnant women. This may cause uterine contractions and fetal heart rate decelerations, which spontaneously resolve within 24 h. Steroids are not effective in reducing these effects and are usually only initiated 24 h prior to antibiotic therapy for cardiovascular syphilis, neurosyphilis or ophthalmological involvement in order to prevent complications arising from acute local inflammation.

Recommended regimens for syphilis during pregnancy can be found in Box 3.

Box 3.

Recommended regimens for syphilis during pregnancy.

Early syphilis

First-line treatment

– Benzathine penicillin 2.4 MU im. single dose in the first and second trimesters

– Benzathine penicillin 2.4 MU im. two doses 1 week apart if maternal treatment initiated in the third trimester

– Procaine penicillin G 600,000 units im. daily for 10 days

Second-line treatment

– Amoxycillin 500 mg p.o. q.d.s. plus probenecid 500 mg p.o. q.d.s. for 14 days

– Ceftriaxone 500 mg im. daily for 10 days

– Azithromycin 500 mg p.o. daily for 10 days

– Erythromycin 500 mg p.o. q.d.s. for 14 days

Late syphilis (for late latent, cardiovascular or gummatous syphilis)

First-line treatment

– Benzathine penicillin 2.4 MU im. weekly for 2 weeks (three doses)

– Procaine penicillin 600,000 units im. daily for 17 days

Second-line treatment

– Amoxycillin 2 g p.o. t.d.s. plus probenicid 500 mg p.o. q.d.s. for 28 days

Neurosyphilis

First-line treatment

– Procaine penicillin 1.8–2.4 MU im. daily plus probenecid 500 mg p.o. q.d.s. for 17 days

– Benzylpenicillin 18–24 MU daily, given as 3–4 MU intravenously every 4 h for 17 days

Second-line treatment

– Amoxycillin 2 g p.o. t.d.s. plus probenecid 500 mg p.o. q.d.s. for 28 days

– Ceftriaxone 2 g im. daily for 10–14 days.

Partner notification is essential. Management should involve close liaison between genitourinary medicine, obstetrics and pediatrics. Both the mother and baby require close monitoring and follow-up.

Viral infections

Genital herpes

Both HSV types 1 and 2 can cause genital herpes. Genital herpes is the most common ulcerative STI in the UK. The presence of genital ulcers also increases the likelihood of HIV transmission [18].

Disease episodes may be first-episode or recurrent, and symptomatic or asymptomatic. First-episode genital herpes is subdivided into primary (newly acquired infection) and non-primary infection (first clinical episode of a previously acquired herpes infection). It can be difficult to distinguish primary infection from the first clinically apparent episode of a previously acquired infection. Primary genital herpes can be very painful and distressing. Most clinicians make a clinical diagnosis and prescribe empirical treatment after taking swabs for HSV. Full STI and HIV screening is important, but swabs are usually deferred until the lesions have healed.

The diagnosis is confirmed by obtaining a swab from the base of an ulcer. HSV DNA detection by PCR is more sensitive than culture [19]. PCR can distinguish HSV-1 from HSV-2. Serology can be difficult to interpret and may not become positive for 6–8 weeks after a primary episode. Routine serology has poor specificity. Type-specific serology is expensive and type-1-seropositivity fails to differentiate between oropharyngeal and genital herpes infections.

The main risks of genital herpes during pregnancy are first or second trimester miscarriage and neonatal herpes. The highest risk of neonatal herpes is in women who acquire HSV during the third trimester. A prospective study of 58,000 women in the USA found 202 cases where HSV was isolated at the time of labor [20]. There were ten cases of neonatal herpes. Transmission is usually from direct contact with the virus during delivery; in utero transmission can occur but is rare. Untreated neonatal herpes is associated with a high mortality and can cause disability even with appropriate timely treatment.

Treatment of HSV in pregnancy

General advice includes saline bathing and analgesia. Management of genital herpes in pregnancy is determined by the gestation of the pregnancy at the time of herpes acquisition and can be categorized into management of first episodes and recurrent episodes. However, this can be difficult to distinguish clinically. Obtaining paired serum samples for type-specific serology several weeks apart may be useful to demonstrate seroconversion (i.e., recent infection).

First-episode genital herpes in first or second trimester

If first-episode genital herpes occurs in the first or second trimester, there is an association with miscarriage but there is no conclusive evidence that it causes birth defects. A 3–5 day course of aciclovir should be used to reduce the severity and duration of the episode. Although aciclovir is not licensed for use in pregnancy, it appears to be relatively safe [21].

Prophylactic suppressive aciclovir from 36 weeks gestation may be considered in order to reduce the likelihood of a HSV outbreak at labor, ultimately reducing the likelihood of Cesarean section [22].

In the absence of lesions or prodromal symptoms at labor, vaginal delivery should be anticipated.

First-episode genital herpes in third trimester

The risk of neonatal herpes is greatest when the mother acquires herpes in the third trimester. The mother acquires herpes but is unable to develop IgG antibodies before delivery and so the baby is born without the protection of passive immunity. In this situation, there is a 30–50% risk of neonatal herpes [22,23]. Therefore, all women with first-episode genital herpes at the time of delivery or within 6 weeks of the expected date of delivery should be offered Cesarean section [102]. However, there are no published randomized controlled trials evaluating the effectiveness of Cesarean section for the prevention of neonatal herpes.

Recurrent genital herpes

Pregnant women who acquired HSV prior to pregnancy will already have IgG antibodies to HSV and will pass these antibodies to the fetus. Neonatal herpes is uncommon in this situation. If there are HSV lesions at the time of vaginal birth, the risk of neonatal herpes is reported to be 2–5% [24]. There is a small risk of asymptomatic shedding and the risk of neonatal herpes in these cases is reported to be 0.02–0.05% [24,25]. Suppressive aciclovir should be considered from 36 weeks until delivery in order to prevent clinical recurrences and therefore reduce the need for Cesarean section [26]. Cesarean section should be considered if there are genital lesions at the onset of labor. Vaginal delivery should be anticipated if there are no lesions present at delivery. The risk of neonatal herpes following vaginal delivery is small and one must balance this against the risk of Cesarean section to the mother [24].

Recommended regimens for HSV can be found in Box4 (see text as above).

HPV

Genital warts are caused by infection with HPV and are the most prevalent viral STI diagnosed in the UK. Infection may not be clinically apparent.

There are over 100 documented HPV genotypes of which approximately 40 are tropic for anogenital skin. Most anogenital warts are benign; however, there are certain genotypes that are associated with an increased risk of anogenital neoplasia, specifically, genotypes 16 and 18 are associated with the greatest risk. External warts are generally due to types 6 and 11, which are not considered to be oncogenic. However, warts can also be caused by other oncogenic strains [27,28]. The most important risk of HPV infection to women is the risk of anogenital cancer. The recent introduction of HPV vaccination programs has led to a significant decrease in high-grade smear abnormalities [29]. Quadrivalent HPV vaccination has also resulted in decreased incidence of genital warts [30].

Genital warts may increase in size and number during pregnancy. The diagnosis is usually made clinically upon visual inspection. Maternal infection is associated with juvenile laryngeal papillomatosis in the infant. This is a rare condition that can cause hoarseness and respiratory distress in children. Cesarean section is not indicated in mothers with genital warts as vertical transmission of HPV is rare [31].

Treatment of HPV during pregnancy

The same as in nonpregnant patients, treatment is usually for cosmetic rather than medical purposes in the majority of cases. Treatment is only really necessary in the unlikely event that the warts cause obstruction of the birth canal and impede vaginal delivery. All treatments have significant failure and relapse rates [32] and no single treatment is considered to be better than another. Cryotherapy with liquid nitrogen causes cytolysis at the dermo—epidermal junction and is safe for use in pregnancy. A freeze/thaw technique should be employed, whereby liquid nitrogen is applied for approximately 10 s until a halo of freeze develops a few millimetres around the wart. This is repeated three or more times for each lesion during the treatment session. Cryotherapy can be administered every 1–2 weeks. Lesions may regress after delivery without any treatment. Podophyllin, podophyllotoxin and imiquimod should be avoided in pregnancy. Contact tracing is not required.

Box 4.

Recommended regimens for herpes simplex virus.

Episodic treatment

Aciclovir 400 mg t.d.s. p.o. for 3–5 days

Suppressive treatment (from 36 weeks)

Aciclovir 400 mg b.i.d. p.o. until delivery

Protozoal infections

T. vaginalis

T. vaginalis is a flagellated protozoan. Women may experience offensive discharge, dysuria and vulval irritation but may also be asymptomatic. Infection in pregnancy is associated with premature delivery and low birth weight [33,34]. Neonatal infection is uncommon but should be considered in infants with vaginal discharge or unexplained respiratory disease. Nasal secretions, tracheal secretions, urine and vaginal swabs from the neonate should be closely examined for trichomonads [35].

The diagnosis is confirmed by direct microscopy of a wet-mount preparation of vaginal secretions from the posterior fornix. This method of diagnosis is routinely employed in genitourinary medicine clinics. Microscopy has a sensitivity of approximately 70% [36]. Culture of vaginal secretions using specific media is more sensitive but rarely available now. Highly sensitive PCR techniques have been developed but are not yet in routine use.

Treatment of T. vaginalis during pregnancy

Metronidazole is the drug of choice and is highly efficacious. Metronidazole appears to be safe for use during the first trimester of pregnancy [37]. The British National Formulary advises avoiding high-dose metronidazole in pregnancy. Patients should be advised to abstain from alcohol while taking metronidazole and for 48 h afterwards because of possible disulfiram-like reaction.

Recommended regime for T. vaginalis can be found in Box 5.

Box 5.

Recommended regime for Trichomonas vaginalis.

Metronidazole 400–500 mg b.i.d. p.o. for 5–7 days

Patients should be advised to abstain from intercourse until they and their partner have been successfully treated. It is the authors' practice to perform a test of cure 1 week later in all cases.

Other

Bacterial vaginosis

Bacterial vaginosis is not regarded as an STI but its prevalence is higher in sexually active women. Bacterial vaginosis is a condition resulting from replacement of the usual H₂O₂ lactobacilli in the vagina with anaerobic bacteria such as Mobiluncus sp. and Gardnerella vaginalis. It is a common cause of vaginal discharge in women of childbearing age but 50% of patients may be asymptomatic. A prevalence rate of 12% was found in pregnant women attending an antenatal clinic in the UK [38]. The pathophysiology, particularly in the context of pregnancy, is poorly understood [39]. Bacterial vaginosis is associated with increased risk of preterm delivery, postpartum endometritis and pelvic inflammatory disease [40].

The diagnosis can be confirmed using either clinical (Amsel's) criteria or Gram stain (Nugent or Hay-Ison) criteria. Amsel's criteria require at least three out of four of the following to be present: thin, white homogeneous discharge, clue cells on microscopy of wet mount, pH of vaginal fluid >4.5 or release of fishy odor upon adding alkali (10% potassium hydroxide) [41]. This so-called amine or ‘whiff’ test is not often performed in genitourinary medicine clinics now for health and safety reasons.

The Nugent score is determined by estimating the relative concentration of bacterial morphotypes that occur in bacterial vaginosis [42]. UK guidelines recommend using the Hay-Ison criteria:

Grade 1/normal: Lactobacillus morphotypes predominate;

Grade 2/intermediate: mixed flora with some lactobacilli present, but Gardnerella or Mobiluncus morphotypes also present;

Grade 3/bacterial vaginosis: predominantly Gardnerella and/or Mobiluncus with few or absent lactobacilli [43].

Box 6.

Recommended regime for bacterial vaginosis in pregnancy.

Metronidazole 400–500 mg b.i.d. p.o. for 5–7 days

Treatment of bacterial vaginosis in pregnancy

Symptomatic women should be treated. However, the same as in nonpregnant women, asymptomatic pregnant women may opt for treatment if offered.

There are conflicting data regarding the value of screening and treating bacterial vaginosis in pregnancy. Evidence from systematic reviews does not support the routine screening and treatment of pregnant women with bacterial vaginosis [44]. However, other data suggest that screening and treating women at high risk for preterm delivery based on their history may significantly reduce the risk for preterm delivery [45 –47].

Metronidazole is the drug of choice and has an estimated cure rate of at least 70% [48]. Alcohol should be avoided during treatment and for 48 h after to prevent a disulfiram-like reaction.

Recommended regime for bacterial vaginosis in pregnancy can be found in Box 6.

Routine screening and treatment of male sexual partners is not required as studies have not shown any effect on likelihood of relapse [49].

Conclusion

Many STIs pose the risk of a number of adverse pregnancy outcomes including miscarriage, still birth, preterm delivery, low birth weight and ophthalmia neonatorum. It should be emphasized that optimal management of any diagnosed STIs in pregnancy should include screening for other STIs and HIV, partner notification and follow-up where appropriate. Close liaison between genitourinary medicine, obstetrics and pediatrics is imperative. Patients should be given a detailed explanation of their condition with particular emphasis on the long-term health implications for themselves, their partners and the infant.

Early diagnosis and treatment of STIs not only alleviates symptoms and reduces complications, but also reduces the period of infectivity and onward transmission.

Future perspective

More emphasis needs to be placed on primary prevention of STIs with healthcare workers playing a key role in improving awareness and promoting sexual health.

Increasing resistance to antibiotics, including third-generation cephalosporins, will make treatment for gonorrhea more challenging.

Current data regarding the value of screening for bacterial vaginosis in pregnancy is conflicting. More research is needed to identify if certain groups of pregnant women may benefit from screening and treatment of bacterial vaginosis.

Currently, only HIV, syphilis and hepatitis B are routinely screened for in UK antenatal clinics. Further work is needed to evaluate the outcomes of screening for other STIs known to have adverse effects in pregnancy.

Executive summary

Background

Sexually transmitted infections (STIs) constitute a major public health concern in the UK.

STIs during pregnancy may be detrimental to both the mother and baby.

Close liaison between genitourinary medicine, obstetrics and pediatrics is imperative.

Effective management of an STI includes full screening for other STIs, a test of cure and partner notification where appropriate.

Bacterial infections

Chlamydia trachomatis

– Chlamydia is the most common bacterial STI in the UK with the highest rates among under 25-year-olds.

– Asymptomatic carriage is common.

– Although azithromycin is not licensed for use in pregnancy, there are data to support its safety for use in pregnancy. It is also recommended by the WHO as first-line treatment for chlamydia during pregnancy.

Gonorrhea

– There are growing concerns regarding decreasing susceptibility of gonorrhea to third-generation cephalosporins.

– Intramuscular ceftriaxone with azithromycin cotreatment (regardless of chlamydia result) is now first-line treatment.

Syphilis

– Pregnant women with early-stage syphilis and higher Venereal Disease Research Laboratory result are at higher risk of having an infant with congenital syphilis.

– Treatment in the last trimester is also associated with increased likelihood of congenital infection.

– Parenteral penicillin is the treatment of choice for all stages of syphilis.

Viral infections

Herpes simplex virus

– Risk of neonatal herpes is greatest when the mother acquires herpes simplex infection in the third trimester of pregnancy.

– Neonatal herpes is uncommon in women with known recurrent genital herpes.

– Data from the Aciclovir Pregnancy Registry support its safety for use in pregnant women.

Human papilloma virus

– Warts may increase in size and number during pregnancy.

– Genital warts are usually treated for cosmetic reasons.

– It is unusual for warts to enlarge to the degree that would obstruct vaginal delivery.

– Cryotherapy with liquid nitrogen is safe for use in pregnancy.

– Recent introduction of a quadrivalent human papilloma virus vaccine has led to a falling incidence of high-grade cervical smear abnormalities and genital warts.

Protozoal infection

Trichomonas vaginalis

– Infection during pregnancy is associated with prematurity and low birth weight.

– Metronidazole is the drug of choice.

Other

Bacterial vaginosis

– Bacterial vaginosis is not regarded as an STI, however, it carries an increased risk of preterm delivery, postpartum endometritis and pelvic inflammatory disease.

– Metronidazole is the drug of choice.

– There are conflicting data regarding the value of screening and treating bacterial vaginosis in pregnancy. Current UK guidelines do not support the routine screening of pregnant women.

Footnotes

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

References

Papers of special note have been highlighted as:.

of interest.

of considerable interest.

House of Commons Health Committee. Sexual Health: Third Report of Session 2002–3, Vol. 1. Health Committee Publications, London, UK (2003).

Fleming

Wasserheit

. From epidemiological synergy to public health policy and practice: the contribution of other sexually transmitted diseases to the sexual transmission of HIV infection. Sex. Trans. Infect. 75, 3–17 (1999).

Andrews

Goldenberg

Mercer

. The preterm prediction study: association of second trimester genitourinary chlamydia infection with subsequent spontaneous preterm birth. Am. J. Obstet. Gynecol. 1(83), 662–668 (2000).

Brocklehurst

Rooney

. Interventions for treating genital Chlamydia trachomatis infection in pregnancy. Cochrane Database Syst. Rev. 2, CD000054 (2000).

Hook

Handsfield

. Gonococcal infections in the adult. In: Sexually Transmitted Diseases (4th Edition). Holmes

Sparling

Stamm

(Eds). McGraw-Hill Companies, NY, USA, 627 (2008).

Alger

Lovchik

Hebel

Blackmon

Crenshaw

. The association of Chlamydia trachomatis, Neisseria gonorrhoeae, and group B streptococci with preterm rupture of membranes and pregnancy outcome. Am. J. Obstet. Gynecol. 159(2), 397–404 (1988).

10.

Martin

Cammarata

Van der Pol

. Multicentre evaluation of AMPLICOR and automated COBAS AMPLICOR CT/NG tests for Neisseria gonorrhoeae. J. Clin. Microbiol. 38, 3544–3549 (2000).

11.

Van der Pol B, Ferrero DV, Buck-Barrington L et al. Multicentre evaluation of the BDProbe Tec ET system for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in urine specimens, female endocervical and male urethral swabs. J. Clin. Microbiol. 39, 1008–1016 (2001).

12.

Schachter

Chernesky

Willis

. Vaginal swabs are the specimens of choice when screening for Chlamydia trachomatis and Neisseria gonorrhoeae: results from a multicentre evaluation of the APTIMA assays for both infections. Sex. Trans. Dis. 32, 725–728 (2005).

13.

Demonstrates that self-taken vaginal swabs are of equivalent sensitivity to endocervical swabs.

14.

Chisholm

Mouton

Lewis

Nichols

Ison

Livermore

. Cephalosporin MIC creep among gonococci: time for a pharmacodynamics rethink? J. Antimicrob. Chemother. 65, 2141–2118 (2010).

15.

Data highlighting the issue of decreased susceptibility of gonococci to third-generation cephalosporins.

16.

Furuya

Nakayama

Kanayama

In vitro synergistic effects of double combinations of β lactams and azithromycin against clinical isolates of

Neisseria gonorrhoeae. J. Infect. Chemother. 12, 172–176 (2006).

17.

Sathia

Ellis

Philip

Winston

Smith

. Pharyngeal gonorrhoea — is dual therapy the way forward? Int. J. STD AIDS 18, 647–648 (2007).

18.

Alexander

Sheffield

Sanchez

Mayfield

Wendel

Jr.

Efficacy of treatment for syphilis in pregnancy. Obstet. Gynaecol. 93, 5–8 (1999).

19.

Sheffield

Sanchez

Morris

. Congenital syphilis after maternal treatment for syphilis during pregnancy. Am. J. Obstet. Gynecol. 186, 569–573 (2002).

20.

McFarlin

Bottoms

Dock

Isada

. Epidemic syphilis: maternal factors associated with congenital infection. Am. J. Obstet. Gynecol 170, 535–540 (1994).

21.

Mascola

Pelosi

Alexander

. Inadequate treatment of syphilis in pregnancy. Am. J. Obstet. Gynecol. 150, 945–947 (1984).

22.

Chisholm

Katz

McDonald

Bowes

Jr.

Penicillin desensitisation in the treatment of syphilis during pregnancy. Am. J. Perinatol. 14, 553–554 (1997).

23.

Keet

IPM

Lee

van Griensven

Lange

Nahmias

Coutinho

. Herpes simplex virus type 2 and other genital ulcerative infections as a risk factor for HIV-1 acquisition. Genitourin. Med. 66, 330–333 (1990).

24.

Wald

Huang

Carrell

Selke

Corey

. Polymerase chain reaction for detection of herpes simplex virus (HSV) DNA on mucosal surfaces: comparison with HSV isolation in cell culture. J. Infect. Dis. 188, 1345–1351 (2003).

25.

Brown

Wald

Morrow

Ashley R

Selke

Zeh

Corey

. Effect of serological status and caesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA 289, 203–209 (2003).

26.

Reiff-Eldridge

Heffner

Ephross

Tennis

White

Andrews

. Monitoring pregnancy outcomes after prenatal drug exposure through prospective pregnancy registries: a pharmaceutical company commitment. Am. J. Gynecol. 182, 159–163 (2000).

27.

Safety data supporting use of acyclovir during pregnancy.

28.

Brown

Selke

Zeh

. The acquisition of herpes simplex virus during pregnancy. N. Engl. J. Med. 337, 509–515 (1997).

29.

Scott

Sanchez

Jackson

Zeray

Wendel

Jr.

Acyclovir suppression to prevent caesarean delivery after first-episode genital herpes. Obstet. Gynecol. 87, 69–73 (1996).

30.

Prober

Sullender

Yasukawa

Yeager

Arvin

. Low risk of herpes simplex virus infections in neonates exposed to the virus at the time of vaginal delivery to mothers with recurrent genital herpes. N. Engl J. Med. 316, 240–244 (1987).

31.

Brown

Benedetti

Ashley

. Neonatal herpes simplex virus infection in relation to asymptomatic viral shedding at the time of labour. N. Engl. J. Med. 324, 1247–1252 (1991).

32.

Sheffield

Hollier

Hill

Stuart

Wendel

. Acyclovir prophylaxis to prevent herpes simplex virus recurrence at delivery: a systematic review. Obstet. Gynaecol. 102, 1396–1403 (2003).

33.

Wiley

Douglas

Beutner

External genital warts: diagnosis, treatment and prevention. Clin. Infect. Dis. 35, 210–224 (2002).

34.

Ault

. Human papilloma virus infections: diagnosis treatment and hope for a vaccine. Obstet. Gynecol. Clin. North Am. 30, 809–817 (2003).

35.

Brotherton

Fridman

May

Chappell

Saville

Gertig

. Early effect of the HPV vaccination programme on cervical abnormalities in Victoria, Australia: an ecological study. Lancet 377, 2085–2092 (2011).

36.

First report of an early decrease in high-grade cervical abnormalities within 3 years of the implementation of a national vaccination program.

37.

Donovan

Franklin

Guy

. Quadrivalent human papilloma virus vaccination and trends in genital warts in Australia: analysis of national sentinel surveillance data. Lancet Infect. Dis. 11, 39–44 (2011).

38.

Quadrivalent human papilloma virus vaccine has resulted in decreased burden of genital warts.

39.

Smith

Ritchie

Yankowitz

. Human papilloma virus prevalence and types in newborns and parents. Sex. Trans. Dis. 31, 57–62 (2004).

40.

Beutner

Wiley

. Recurrent external genital warts: a literature review. Papilloma Virus Rep. 8, 69–74 (1997).

41.

Klebanoff

Carey

Hauth

. Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N. Engl. J. Med. 345, 487–493 (2001).

42.

Cotch

Pastorek

2nd Nugent

. Trichomonas vaginalis associated with low birth weight and preterm delivery. Sex. Trans. Dis. 24, 353–360 (1997).

43.

Trintis

Epie

Boss

Reidel

. Neonatal Trichomonas vaginalis infection: a case report and review of literature. Int. J. STD AIDS 21, 606–607 (2010).

44.

Bickley

Krisher

Punsalang

Trupei

Reichman

Menegus

. Comparison of direct fluorescent antibody, acridine orange, wet mount and culture for detection of Trichomonas vaginalis in women attending a public sexually transmitted diseases clinic. Sex. Trans. Dis. 16(3), 127–131 (1989).

45.

Cziezel

Rockenbauer

. A population based case—control teratologic study of oral metronidazole treatment during pregnancy. Br. J. Obstet. Gynaecol. 105, 322–327 (1998).

46.

Hay

Lamont

Taylor-Robinson

Morgan

Ison

Pearson

. Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. Br. J. Med. 308, 295–298 (1994).

47.

Nelson

Macones

. Bacterial vaginosis in pregnancy: current findings and future directions. Epidemiol. Rev. 24, 102–108 (2002).

48.

Hillier

Marrazzo

Holmes

. Bacterial vaginosis. In: Sexually Transmitted Diseases (4th Edition). Holmes

Sparling

Stamm

(Eds). McGraw-Hill, NY, USA, 737 (2008).

49.

Amsel

Totten

Spiegel

Chen

Eschenbach

Holmes

. Non-specific vaginitis. Diagnostic criteria and microbial and epidemiological associations. Am. J. Med. 74, 14–22 (1983).

50.

Nugent

Krohn

Hillier

. Reliability of diagnosing bacterial vaginosis is improved by a standardised method of Gram stain interpretation. J. Clin. Microbiol. 29, 297–301 (1991).

51.

Ison

Hay

. Validation of a simplified grading of gram stained vaginal smears for use in genitourinary medicine clinics. Sex. Trans. Infect. 78, 413–415 (2002).

52.

Nygren

Freeman

Bougatsos

Klebanoff

Guise

. Preventative services task force. Evidence on the benefits and harms of screening and treatment patients who are asymptomatic for bacterial vaginosis: an update review for the US Preventative Services Task Force. Ann. Intern. Med. 148, 220–233 (2008).

53.

Meta-analysis that did not find any benefit in screening and treating low-risk women with asymptomatic bacterial vaginosis.

54.

Hauth

Goldenberg

Andrews

DuBard

Copper

. Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. N. Engl. J. Med. 333, 1732–1736 (1995).

55.

McDonald

O'Loughlin

Vigneswaran

. Impact of metronidazole therapy on preterm birth in women with bacterial vaginosis flora (Gardnerella vaginalis): a randomised placebo-controlled trial. Br. J. Obstet. Gynaecol. 104, 1391–1397 (1997).

56.

Morales

Schorr

Albritton

. Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study. Am. J. Obstet. Gynecol. 171, 345–349 (1994).

57.

Koumans

Markowitz

Hogan

. For the CDC BV Working Group. Indications for therapy and treatment recommendations for bacterial vaginosis in non-pregnant and pregnant women: a synthesis of data. Clin. Infect. Dis. 35, S152–S172 (2002).

58.

Colli

Landoni

Parazinni

. Treatment of male partners and recurrence of bacterial vaginosis: a randomised trial. Genitourin. Med. 73, 267–270 (1997).

59.

Health Protection Agency (HPA) data. www.hpa.org.uk.

60.

NICE clincial guidance: routine care for the healthy pregnant woman (2008). www.nice.org.uk

61.

British Association of Sexual Health and HIV guidelines. www.bashh.org

Managing Sexually Transmitted Infections in Pregnant Women

Abstract

Keywords

Bacterial infections

C. trachomatis

Treatment of chlamydia during pregnancy

Gonorrhea

Treatment of gonorrhea during pregnancy

Syphilis

Treatment of syphilis during pregnancy

Viral infections

Genital herpes

Treatment of HSV in pregnancy

First-episode genital herpes in first or second trimester

First-episode genital herpes in third trimester

Recurrent genital herpes

HPV

Treatment of HPV during pregnancy

Protozoal infections

T. vaginalis

Treatment of T. vaginalis during pregnancy

Other

Bacterial vaginosis

Treatment of bacterial vaginosis in pregnancy

Conclusion

Future perspective

Footnotes

References