Non-viral sexually transmitted infections in pregnancy: current controversies and new challenges

Abstract

Purpose of the review:

This review provides an update of non-viral, curable sexually-transmitted infections (STIs) in pregnancy and summarizes our understanding of the current issues and controversies surrounding risk factors, screening, and treatment of STIs in pregnancy in high-income countries (using the United States and the United Kingdom as examples). The infections covered in this review are syphilis, gonorrhea, chlamydia, trichomoniasis, and Mycoplasma genitalium infections.

Recent findings:

Overall, limited modern data is available to update researchers and clinicians on the epidemiology and care of STIs in pregnancy. Though common risk factors can be identified among these STIs, like socio-economic status and inadequate antenatal care, specific screening and treatment challenges vary by geography and pathogen. Where available, surveillance data and research evidence are often limited to non-pregnant patients, leading to imperfect pregnancy-specific risk estimates and obstetric lags in the development and adoption of new guidelines. We have identified three areas of opportunity that may enhance the effectiveness of current approaches and inform new ones: 1) improved data collection and evidence-based screening practices; 2) prompt and comprehensive therapy, including partner services, and evaluations of new treatment modalities; 3) equitable antenatal and sexual health care for all pregnant persons and their partners.

Summary:

These findings highlight the need to revisit standards of screening and management of STIs in pregnancy in high-income countries.

Introduction

Syphilis, gonorrhea, chlamydia, trichomoniasis, and Mycoplasma genitalium infections, are non-viral curable sexually-transmitted infections (STIs) that are common among females. Though frequently asymptomatic, which delays diagnosis and treatment, these STIs are associated with inflammation in the genital tract and increased Human Immunodeficiency Virus (HIV) acquisition risk ^[1,2]. Left untreated, they are associated with reproductive, obstetric and fetal sequelae, including pelvic inflammatory disease (PID), preterm labor and preterm birth, low birthweight, and congenital infections ^{[3**,4**,5**,6**,7**,8,9**]}. Here, we review recent data on epidemiologic trends, and screening and treatment guidelines from high-income countries, as defined by the World Bank, using the United States and United Kingdom as our most frequent examples. We attempt to synthesize some pregnancy-specific themes regarding these STIs and highlight knowledge and practice gaps and opportunities. Due to a scarcity of published data sources overall, we expanded our review period to include the years 2009–2020, while also citing key studies from the decade prior (2000–2009).

Overview of challenges

Scarcity of pregnancy-specific STI data

There is limited official surveillance data on STIs in pregnancy ^[10,11,12]. Rates of STIs in pregnancy have typically been extrapolated from the general female population of child-bearing age ^[10,11]. Of the STIs discussed herein, syphilis has the most reliable pregnancy-specific estimates globally, due to efforts to curb rising congenital syphilis through an uptake in antenatal screening and, in some countries, the integration of syphilis and HIV programs ^[13]. The most recent report of US national trends of STIs in pregnancy is a retrospective analysis of all births records between 2016–2018 with specified maternal STIs. The study revealed that the rates of chlamydia, gonorrhea, and syphilis among pregnant females were 1,830.9, 291.0, and 101.7 per 100,000 births, respectively ^[14**], higher than the rates per 100,000 females in the general population during the same period (chlamydia 676.2, gonorrhea 135.6, and syphilis 2.4) ^[15*], though the discrepancy in syphilis rates may also reflect universal syphilis screening in US pregnancies. Comparable sources of national pregnancy-specific statistics were not available for non-notifiable infections (trichomoniasis or Mycoplasma genitalium infections) or for the notifiable infections (gonorrhea, chlamydia, and syphilis) in other high-income countries, like the UK, Australia, Canada, or Ireland (trichomoniasis is notifiable in Ireland). For example, the official 2019 STI statistics from England and Northern Ireland do not report pregnancy-specific STI rates ^[16,17], which are instead given as an aggregate for reproductive-aged females. Pregnancy status identification in the US is possible but not required for either chlamydia or gonorrhea reporting ^[10], which may lead to official statistics underestimating their true burden ^[14**]. Thus, epidemiologic metrics of STIs in pregnancy are lacking. Cohort research studies exist and partly fill these knowledge gaps but are not always representative of general trends because they analyze specific sub-populations ^{[9**,18,19,20,21,22,23,24**,25**,26*]}.

The impetus for improving pregnancy-specific data is three-fold. First, undetected and untreated STIs during pregnancy are associated with adverse maternal and fetal/neonatal outcomes ^{[3**,4**,5**,6**,7**]} (Table 1). However, the degree to which certain STIs mediate a causative influence on these outcomes (e.g. timing of chlamydia and risk of preterm birth) remains uncertain ^[4**]. Second, for those STIs that show a clear and strong association with poor pregnancy and birth outcomes (e.g. gonorrhea and trichomoniasis, Table 1), there is insufficient or imperfect evidence to demonstrate that the current therapies used in pregnancy are effective in mitigating these effects ^[6**,27*]. Finally, STI rates are rising, a phenomenon that has coincided with a rise in resistance to available therapeutics for gonorrhea, and with an increase in congenital syphilis ^[15*].

Table 1.

Evidence of the relationship between pathogens and adverse reproductive, pregnancy, and fetal/neonatal outcomes.

Infection (pathogen)	Pelvic inflammatory disease	Ectopic pregnancy	Adverse Maternal and Neonatal Outcomes						Effect of maternal treatment on outcomes
			Preterm premature rupture of the membranes	Preterm birth	Stillbirth	Low birthweight	Congenital infections	Chorioamnionitis
Syphilis (Treponema pallidum)	Unknown association/ risk*	Unknown association/ risk	Increased risk [28]	Increased risk [7**]#	Increased risk [7**]#	Increased risk [7**]#	Congenital syphilis (and impaired fetal growth, fetal and neonatal demise) [7**]#	Known association, but rare outcome [29]	Reduction in premature birth following penicillin treatment in pregnancy [28,30]; reduction in perinatal death, and stillbirth following penicillin treatment in pregnancy [30,31]#
Gonorrhea (Neisseria gonorrhoeae)~	Causative [24**,32,33]	Increased risk [9**]	Increased risk [28] [34]^	Most likely associated, but timing of infection during gestation is a confounder and may be important to clinical outcome. Increased risk [8,28,35] [36]% No association [6**]∨	Increased risk [8,28]	Increased risk [6**]	Vertical transmission occurs in 30–50% of maternal cases and leads to ophtalmia neonatorum [37,38]^ [39,40] and mucosal infections [37]^	Inconclusive, but the robust neutrophil response in gonorrhea [41] would support this association. Not associated [42] [6**]∨ Increased risk [34]^	While high levels of maternal cure of gonorrhea in pregnancy are observed with various antibiotic regimens (and it is assumed that this is effective in preventing transmission to the newborn), there is limited randomized controlled trial evidence that supports specific regimens [27*]# or demonstrates decreased neonatal infections and improved obstetrics outcomes, mainly because these outcomes are seldom reported [43,44]^.
Chlamydia (Chlamydia trachomatis)	Causative [24**,45,46]	Increased risk [9**,46] [4**]#	Inconclusive Increased risk [8] Not associated [28] Weaker association in high-income countries [4**]#	Inconclusive Increased risk with chlamydia history [8] or current chlamydia in pregnancy [47] Not associated with current chlamydia in pregnancy [25**,28] Weaker association in high-income countries [4**]#	Inconclusive Increased risk with chlamydia history [8] Not associated with current chlamydia in pregnancy [25**] Weaker association in high-income countries [4**]#	Weaker association in high-income countries [4**]#	Conjunctivitis [37,38]^ [39,40]	Not associated in an adolescent pregnant population [42]	While microbiological cure of maternal infections appears to be achieved with a variety of regimens (and it is assumed that this is effective in preventing transmission to the newborn), there is no consensus on best regimen [48*] #. Improvements of other obstetric and neonatal outcomes following treatment remains unclear [48*]#.
Trichomoniasis (Trichomonas vaginalis)	Associated [49]	Unknown	Increased risk [3**] #	Increased risk [3**] #	Unknown [50,51]^	Increased risk [3**] #	Neonatal infections are uncommon, but case reports have documented Neonatal pneumonia [52,53]^ and neonatal vaginitis [54*,55]^	Increased risk in an adolescent pregnant population [42]	Metronidazole treatment in pregnancy may provide parasitological cure, but it is not yet known whether current regimens improve perinatal outcomes[42,56,57,58*] , as some of the available evidence is not free from confounders [56,57]^. This includes one prematurely stopped trial }[56]^ that showed an unexpected increased risk of preterm birth in the metronidazole treatment arm, and thus warrants caution when interpreting its findings [56]^.
Mycoplasma genitalium infections	Causative [33,59,60]	Possible increased risk [61], but data are scarce	Unknown	Increased risk [5**] #	No association, but data are scarce [62,63]	Unknown	Unknown	Unknown	Unknown

^#We are citing here results from meta-analyses. Cross-reference their bibliography references for original data articles, which may pre-date the period included in this review.

^~There are no published meta-analyses that have quantified the degree of association between Neisseria gonorrhoeae and adverse pregnancy and perinatal outcomes, but the first is in preparation ^[64].

^*Pelvic inflammatory disease (PID) is a complication of untreated or undertreated cervicitis. The US CDC does not explicitly recommend syphilis screening for PID-diagnosed women ^[65], and thus the rates of syphilis in females with PID may be understudied; for example, in one study of general emergency department patients diagnosed with PID only 31% of those screened for gonorrhea and chlamydia were also screened for syphilis ^[66].

^{^}Available evidence pre-dates the review period.

^∨Limitation of this study was unknown timing of gonorrhea diagnosis during gestation.

^%Association was stronger when gonorrhea diagnosis was in the first trimester.

Risk factors

Globally, the socially disadvantaged, who may have limited access to prompt and adequate health care, carry the highest burden. The traditional STI risk factors include younger age, racial or ethnic minority membership, lower socio-economic status, lack of insurance, drug and alcohol use, transactional sex, and intimate partner violence. These have also been identified in pregnancy ^{[10,14**,26*,67,68**]} and are barriers to accessing antenatal care ^[14**]. Inadequate prenatal care is, in turn, one of the strongest predictors of poor pregnancy and neonatal outcomes due to undetected or untreated STIs, even in high-income countries ^{[10,14**,67,69]}.

Pregnancy itself may be associated with an increased risk of pathogen acquisition ^[70], including HIV ^[71] and chlamydia ^[72]. The immuno-tolerant nature of pregnancy has been well-documented ^[73,74], which may contribute to increased pathogen susceptibility ^[74]. Pregnancy may also enhance the transmissibility of STIs, as pregnant women report lower rates of condom use ^[75], though less sexual activity and less risky sex behaviors may offset this risk ^[76].

STI screening in pregnancy

Screening guidelines differ internationally (particularly for syphilis ^[77]), making the comparison of population-specific statistics difficult. This is compounded by biological factors of each organism, like diagnostic-escape variants for chlamydia, which may emerge and remain persistently undetected in a single country or region ^[78,79,80]. Integrated screening for STIs and HIV in pregnant persons remains an untapped opportunity to address the STI-HIV syndemic in pregnancy, as has been proposed for HIV and syphilis ^[13]. Combined gonorrhea and/or chlamydia and HIV screening was associated with diminished risk of mother-to-child-transmission of both HIV and the STI ^[81,82]. For a recent review of screening for STIs in pregnancy in low-to-middle-income countries, with identification of research priorities, see Grant et al. ^[83].

Reinfections

Reinfections with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis are common among treated non-pregnant ^[84**] and pregnant females ^[26*,85,86*]. Risk factors for reinfection among all females are younger age, exposure from an untreated sexual partner, and coinfection with other STIs (reviewed in Hosenfeld et al. ^[84**]). The United States Centers for Disease Control (US CDC) recommends post-treatment retesting within three months for all C. trachomatis and N. gonorrhoeae-positive persons, and for all T. vaginalis-positive females ^[87]. Repeat testing and partner services are two pillars in the STI care continuum ^[87,88], and in the antenatal context, timely adherence to these guidelines is crucial. A large retrospective study of chlamydia and gonorrhea clinical diagnoses among 1.3 million pregnant US females during 2005–2008 showed that only two thirds of pregnant patients initially positive for chlamydia or gonorrhea were re-tested ^[68**]. Partner notification and expedited partner therapy (EPT) are two types of partner services models. Currently in the UK, sexual partners of diagnosed STI patients are notified of the STI exposure by health ^[89]. With EPT, a provider prescribes the indicated therapy for a patient’s partner without examining the partner ^[90]. Three RCTs, including two with female participants, and a meta-analysis have shown EPT is associated with lower STI re-infection rates ^{[91**,92**,93**,94]} and has been endorsed by the American College of Obstetricians and Gynecologists (ACOG) and the US CDC. Despite its demonstrated efficacy, implementation of EPT is hindered by numerous factors. It is legally permissible for gonorrhea and chlamydia only and only in 45/50 US states. In the UK it does not comply with current prescribing guidance ^[95], though other enhanced models of routine PT are being investigated here ^[89]. Practical considerations also limit EPT application, as many obstetric and midwifery practices do not have the provider capacity or administrative ability to treat male partners, particularly when in-person administration of parenteral medications is required. Recommendations for N. gonorrhoeae EPT may also change with trends in antibiotic resistance patterns. While repeat syphilis infections, even during the same pregnancy, have been reported ^[96**], no published evidence supports EPT for syphilis, which also requires clinical assessment of stage for treatment option decisions. The US CDC has recognized the utility of EPT for trichomoniasis ^[87], though US laws allowing for EPT do not include T. vaaginalis, leaving many prescribers hesitant to offer it.

Barriers to treatment of non-viral STI in pregnancy

Most antibiotics approved or recommended for use in the treatment of STI, including penicillin, ceftriaxone, azithromycin, and metronidazole, are rated as category B for use in pregnancy, indicating there are no animal or human studies demonstrating fetal risk. Though largely believed to be safe, the decision to treat pregnant patients with these agents needs to be supported by evidence of either maternal, fetal, or neonatal infant benefit from the treatment (see Table 1). Additionally, drug shortages highlight the importance of provider knowledge of alternative therapies, improved disease surveillance to guide drug need forecasting, and new research into treatment modalities. For example, a global shortage of benzathine penicillin G, the recommended therapy for most stages of syphilis, occurred between 2014–2019, affecting the US and Australia ^[97]. In the US in 2020 there is an ongoing shortage of azithromycin tablets and erythromycin ophthalmic ointment. US drug shortages are monitored by the US CDC https://www.cdc.gov/std/treatment/drug-notices.htm.

Specific pathogens

Treponema pallidum

Of the curable STIs, syphilis is the most consistently screened for in pregnancy ^[98] due to risk of congenital infections, prematurity, low birthweight, stillbirth, and neonatal demise ^[7**]. Syphilis was the least reported notifiable STIs among pregnant women in the US between 2016 and 2018 ^[14**], but data on exact screening rates were not found. Antenatal syphilis testing is mandatory in most US states, though timing and frequency of screening is highly variable ^[99*].

Congenital syphilis is a potentially severe consequence of untreated maternal syphilis infection (Table 1, reviewed in ^[100]). Congenital syphilis rose by 184% between 2014 and 2018 (1,306 cases in 2018) ^[15*], coinciding with an increase in primary and secondary syphilis cases in US reproductive-aged women ^[15*]. In the US, a quarter of congenital syphilis can be attributed to lack of antenatal care and 42% to delayed treatment ^[101]. A total of 21 congenital syphilis cases were reported between 2010 and 2017 in the UK, ^[102,103], where screening coverage was 99% in 2017 ^[69]. These few cases were attributed to limited access to antenatal care and acquisition following a negative first trimester test ^[69]. The latter, combined with reports of repeat syphilis infections during the same pregnancy ^[96**], support repeat testing during pregnancy, which ACOG ^[104] and US ^[65] recommend. In the US, UK, and some European non-antenatal settings the use of reverse screening algorithms is increasing ^{[106,107,108]}, albeit with some differences ^[109]. Though these algorithms have been studied in the general population, limited data support their use in pregnancy ^[110*], so implementation in obstetrics has lagged. Furthermore, rapid point-of-care tests exist ^[111,112], but their accuracy and usefulness in the antenatal setting remains to be ascertained ^[113].

Neisseria gonorrhoeae

The incidence of gonorrhea in the US and the UK is on the rise ^[15*,16,114]. We found a readily available US data source for gonorrhea in pregnancy ^[14**], in which the authors used all 2016–2018 birth records with specified STI rates to find that Ng infection rates were 310.2/100,000 births, higher than in the general female population during the same period of 135.6/100,000 ^[15*]. In England, heterosexual women accounted for a quarter of all cases in 2019 (17,826/70,936), which increased 26% since 2018 ^[114]. Published pregnancy-specific national data sources were not found for the UK or Australia.

The ACOG and US CDC recommend screening for those <25 years and for all high-risk patients at the initial visit and again in the third trimester ^[104], but compliance with these guidelines is imperfect; among 1.3 million pregnant US females between 2005–2008 only 40% were tested at the first visit and among pregnant females <25years only 22% were re-tested ^[68**]. Risks for inadequate screening include insufficient antenatal care, lack of insurance, care transfers, and clinician-deferred testing to a subsequent visit ^[68**]. Once patients screen positive, treatment should be promptly initiated, as delays >1 week may be associated with an increased risk of preterm birth compared to timely treatment (<1 week) ^[26*]. Treatment delays are largely attributable to provider delay (65%) or difficulty contacting the patient (33%) ^[26*].

Treatment recommendations for gonorrhea in pregnancy vary between high income countries like US and UK, oftenr guided by local antibiotic resistance prevalence ^{[104, 115, 116]}. In spite of strong associations with preterm birth, stillbirth, low birthweight and preterm premature rupture of the membranes (Table 1), evidence that demonstrates improved maternal and fetal/neonatal outcomes following treatment regimens currently used in pregnancy is insufficient ^[27*,43,44]. With increasing rates of antimicrobial resistance, including ceftriaxone resistance, developing and evaluating new pregnancy-safe therapies is an urgent need. Gentamicin has been proposed as an alternative for uncomplicated N. gonorrhoeae infection, but two randomized control trials reported conflicting results on efficacy ^[117**,118*]. Further, gentamicin is rated pregnancy Class D for known fetal risk of hearing loss when used in pregnancy, thus use in pregnancy is reserved for infections in which no safe alternative antibiotic is available.

Chlamydia trachomatis

C. trachomatis is the most common bacterial STI in the world and is detected more commonly in women than in men ^{[4**,119,120]}. Screening guidance for chlamydia in pregnancy varies among countries. This may be a reflection of conflicting evidence from high-income countries ^{[4**,121,122]} regarding the relationship with preterm birth, preterm premature rupture of the membranes, and low birthweight (Table 1), with timing of infection (before, during early, or late gestation) confounding analyses of causation and decisions around optimal timing of routine screening. There is also uncertainty regarding improved maternal and fetal/neonatal outcomes following chlamydia treatment ^[48*] and cost effectiveness ^[104]. The Canadian Public Health Agency recommends universal screening of pregnant women ^[123], the US CDC recommends screening of women <25years and high-risk pregnant women at the first visit and again in the third trimester ^[65], and the NHS in the UK recommends against routine screening ^[124]. Recent studies affirm that treating chlamydia does not confer additional pregnancy risk ^[24**].

Azithromycin, FDA approved for treatment of cervicitis caused by C. trachomatis, is the preferred regimen in pregnancy, as the alternative, doxycycline, is contraindicated due to teratogenicity ^[87]. Cure rates in pregnant persons have been reported to be lower than in non-pregnant women, and often attributed to use of amoxicillin in pregnant patients rather than a proven first-line agent like azithromycin ^[65,125]. The pregnancy risk associated with one dose of azithromycin is unknown, but prevention of the known risk of ophthalmia neonatorum from untreated chlamydia ^[39,40] is generally believed to outweigh the risk of treatment. Universal neonatal prophylaxis against C. trachomatis and N. gonorrhoeae conjunctivitis is not recommended in the UK, Canada, Norway, Sweden, and Denmark ^[126,127], which focus on maternal STI prevention and treatment instead.

Trichomonas vaginalis

Despite high prevalence globally, T. vaginalis remains a neglected parasitic infection ^[128]. Reported trichomoniasis prevalence among US females of reproductive age, including pregnant persons, is 3–7% ^[85,129]. Persistence and/or reinfection after treatment are also common, with positive results in 29% of re-tests when performed >14d after treatment ^[86*] and up to 44% when tests were performed >21d after prescription of treatment ^[85]. This suggests that both a test-of-cure (3–4 weeks after treatment) and a test-of-reinfection (3–4 months after treatment) may be indicated.

Trichomoniasis is not a notifiable infection in the US, UK, or Australia and national screening guidelines for HIV-negative females (including pregnant women) do not currently exist in these countries. In HIV-positive women, trichomoniasis screening and treatment is recommended, as treatment decreases viral shedding in the genital tract ^[130,131] and reduces the risk of HIV mother-to-child transmission. In areas of the US with high trichomoniasis transmission clinicians may choose to test asymptomatic pregnant women ^[86*], but the benefits of routine antenatal screening in HIV-negative women have not yet been defined ^[132]. Asymptomatic antenatal screening for T. vaginalis is not recommended in the UK, where trichomoniasis appears to be less common ^[133]. In addition, trials of trichomoniasis treatment with metronidazole in pregnancy have yet to demonstrate improvements in obstetric outcomes ^[58*,134] (reviewed in ^[135]), despite compelling associations between maternal T. vaginalis in pregnancy and low birthweight, preterm premature rupture of the membranes, preterm labor, prematurity and chorioamnionitis (Table 1), and several case reports of neonatal pneumonia and vaginitis due to T. vaginalis of babies born to mothers with trichomoniasis ^{[52,53,54*,55]}. One of these trials was halted prematurely and suggested an association between preterm delivery and a higher, atypical, metronidazole dosing schedule ^[56], however subsequent studies have not validated this association ^[58*,134], raising questions whether this was a real effect ^[135]. Given the strong link between trichomoniasis and adverse pregnancy and neonatal outcomes, it is vital we investigate safe and effective ways to identify and treat T. vaginalis infections in pregnancy.

Recently, a randomized, open-label trial in non-pregnant HIV-positive females found that 500 mg metronidazole administered orally twice daily for seven days was superior to the standard treatment of 2g metronidazole administered orally once ^[136**]. The ACOG subsequently updated treatment recommendations for trichomonal vaginitis in non-pregnant women (ACOG Practice Bulletin #215, 2020); however, the safety and efficacy of this longer course of metronidazole has not been examined in pregnancy, but the potential safety of the seven-day course is plausible ^[134,137].

Mycoplasma genitalium

The recognition of M. genitalium infection as an important STI has been increasing over the past decade. The association between M. genitalium and non-gonococcal urethritis in men is well established ^[138], but data supporting a causal link between M. genitalium and adverse pregnancy outcomes are inconsistent (Table 1) (reviewed in ^[139]). Inconsistencies may be influenced by the variable reported prevalence of M. genitalium in pregnancy, which also limits the confidence with which associations with clinical outcomes can be identified. The reported M. genitalium prevalence during pregnancy varies by country and demographics and ranges from 0.7% to 20% ^{[62,140,141,142,143,144,145,146]}. A recent meta-analysis showed a significant 2-fold increase in the risk of spontaneous abortion, preterm birth, cervicitis and PID in women with M. genitalium, even when co-infection with other STIs was excluded ^[5**], but the data originated from a small number of observational studies. M. genitalium may be vertically transmitted ^[147]. Additional evidence that M. genitalium antenatal screening and treatment is associated with reduced risk of obstetric sequelae is needed before routine antenatal testing can be recommended. Prior to 2019 when the first diagnostic test for M. genitalium was approved by the FDA, empiric therapy was attempted for recurrent cases of cervicitis and PID. There are no antibiotics approved by US FDA for treatment of M. genitalium infection. US CDC guidelines indicate the preferred treatment for M. genitalium of 1g azithromycin as a single dose produces cure rates of up to 85% ^[87]. In the UK, a 3-day course of azithromycin is recommended for uncomplicated M. genitalium infection in pregnancy ^[148]. In cases of persistent or upper genital tract M. genitalium infection, options for treatment in pregnancy are limited as moxifloxacin, guideline recommended second-line therapy, carries pregnancy Category C label with US FDA. In the UK, guidelines are that M. genitalium treatment may be delayed until after pregnancy with appropriate discussion of risks of infection as well as treatment options ^[148].

Conclusion

STIs during pregnancy are common, but disproportionately burden those who experience significant barriers to accessing healthcare. Each high-income country has chosen to prevent, screen, and treat patients differently, but the success of each strategy is difficult to ascertain, as availability of pregnancy-specific statistics is limited. There is also insufficient data evaluating causal links between STIs and poor maternal and fetal outcomes (infertility, pelvic inflammatory disease, preterm birth, low birthweight, and neonatal demise) and whether current therapies are effective in mitigating these adverse outcomes; syphilis may be the only possible exception. In an era of increasing antimicrobial resistance, evaluating pregnancy-safe treatment regimens is of particular importance. In conclusion, it is clear that better surveillance of STIs in pregnancy and enhanced research effort are required for a robust understanding of epidemiologic trends, of the deleterious effects of STIs to maternal and fetal outcomes, and effective ways to prevent them, all the while maintaining clinical compliance with the most up-to-date STI guidelines, including appropriate levels of testing and re-testing for pregnant persons and their partners.

Key points.

• Significant socio-economic and racial disparities exist, particularly in studies of patients in the US, barriers to antenatal care are predictors of poor pregnancy outcomes.

• Limited pregnancy-specific data precludes reliable incidence estimates in pregnancy.

• Antenatal screening practices are highly variable across countries and regions, and there is an obstetric lag in evaluating and adopting new and improved practices already in use for non-pregnant populations; additional research is needed to identify optimal screening strategies.

• Prompt treatment and re-testing appear to confer improved pregnancy outcomes, which may be further improved with effective partner services, though additional research is needed into new prevention and therapeutic strategies.