Sexually Transmitted Infections in Pregnancy

• Placental invasion and vertical transmission: Certain pathogens exploit the syncytiotrophoblast's naturally increased permeability during pregnancy (especially third trimester) and possess specific tropism for placental tissues. Treponema pallidum (syphilis) crosses the placenta via hematogenous dissemination after maternal spirochetemia, causing direct fetal infection with resultant vasculitis of umbilical vessels and organ damage; congenital syphilis develops in 40-80% of infants born to untreated seropositive mothers. Cytomegalovirus (CMV) and rubella infect placental endothelium, then disseminate to fetal tissues, with CMV causing direct viral replication in multiple fetal organs (liver, kidney, lung) and rubella causing persistent infection with teratogenic effects. Toxoplasma gondii crosses the placenta via trophoblastic parasitemia, with transmission risk inversely proportional to gestational age (15% at 13 weeks, 60% at 36 weeks), though severity inversely correlates with gestational age (severe manifestations in early infection).

• Ascending infection via compromised cervical barriers: Pregnancy-related physiologic changes—progesterone-induced cervical mucus thickening, altered vaginal flora, increased vaginal pH, and mechanical cervical changes—paradoxically create permissive conditions for ascending infection while the cervical mucus plug theoretically provides protection. Chlamydia trachomatis and Neisseria gonorrhoeae possess specific adherence mechanisms to columnar epithelium; they produce proteases degrading secretory IgA and mucosal defense mechanisms, ascending to the endometrium and fallopian tubes where they trigger inflammatory response with prostaglandin production (driving preterm labor). In pregnancy, the endometrial decidua exhibits altered inflammatory responsiveness with increased IL-6, IL-8, and TNF-α production in response to microbial invasion, contributing to premature rupture of membranes (PROM) and spontaneous preterm birth. GBS colonizes the rectovaginal area in 20-30% of pregnant women; ascending infection triggers amnionitis with maternal fever, fetal tachycardia, and neonatal sepsis if intrapartum transmission occurs.

• Immunologic alterations promoting pathogen survival: Pregnancy induces a physiologic Th2-skewed immune response with reduced Th1 cell-mediated immunity and altered dendritic cell function, theoretically supporting fetal acceptance but unfortunately permitting certain pathogen proliferation. Herpes simplex virus establishes latency in dorsal root ganglia with periodic reactivation; pregnancy increases HSV reactivation risk by 2-3 fold due to immunosuppression, and primary HSV infection during pregnancy (especially third trimester) carries 30-50% risk of disseminated maternal infection and neonatal transmission. Human immunodeficiency virus (HIV) replicates in activated CD4+ cells; pregnancy increases HIV viral load and reduces CD4 count by 50-100 cells/mm³, increasing transmission risk to 15-45% without antiretroviral therapy (ART), though maternal viremia suppression reduces transmission to <2%. Regulatory T cells (Tregs) expand during pregnancy via TGF-β signaling, promoting immune tolerance but simultaneously reducing clearance of intracellular pathogens; this mechanism particularly enhances risk for toxoplasmosis and CMV dissemination.

• Placental inflammation and fetal sequelae: Microbial invasion of the intrauterine cavity (MIUC) triggers a cascade of inflammatory mediators—particularly prostaglandins (PGE2, PGF2α), cytokines (TNF-α, IL-1β, IL-6), and chemokines—that induce uterine contractions and cervical ripening, resulting in preterm labor. Fetal inflammatory response syndrome (FIRS), defined by elevated umbilical cord blood IL-6 (>11 pg/mL) or procalcitonin, develops in response to ascending infection and correlates strongly with adverse neonatal outcomes including bronchopulmonary dysplasia, intraventricular hemorrhage, and mortality. Direct fetal infection causes organotropic manifestations: CMV causes hepatosplenomegaly, thrombocytopenia, and microcephaly via direct viral replication and apoptosis in developing neural tissue; rubella causes cardiac defects (patent ductus arteriosus, peripheral pulmonary artery stenosis), cataracts, and sensorineural hearing loss; syphilis causes hepatomegaly, bone periostitis, and neurosyphilis with hydrocephalus.

• Neonatal transmission pathways: Delivery through infected birth canal exposes neonates to pathogenic inoculum, with transmission efficiency varying by organism and delivery method. Chlamydia causes neonatal conjunctivitis (inclusion conjunctivitis) in 30-50% of infants born vaginally to infected mothers, with subsequent risk of chlamydial pneumonia in 5-15%; organism attachment to conjunctival columnar epithelium triggers inflammatory infiltration and mucoid discharge. Gonorrhea causes ophthalmia neonatorum (acute purulent conjunctivitis) in 30-40% of exposed neonates within 2-5 days of birth; if untreated, rapidly progresses to corneal ulceration and blindness due to intensive polymorphonuclear response. HSV transmission during vaginal delivery occurs in 30-50% of neonates born to mothers with primary infection (versus 3-5% with recurrent infection due to maternal antibodies), causing disseminated neonatal herpes in up to 75% of infected neonates, with 15-20% mortality if untreated and 50% of survivors experiencing serious neurologic sequelae.

• Bacterial STIs: Chlamydia trachomatis (serovars D-K for genital infection) is the most common bacterial STI in pregnancy, with prevalence 2-5% in U.S. obstetric populations; transmission occurs during vaginal delivery causing neonatal conjunctivitis and pneumonia. Neisseria gonorrhoeae causes acute purulent urogenital infection with lower prevalence (0.1-2%) but higher pathogenicity for neonatal ophthalmia; ascending infection increases risk of pelvic inflammatory disease (PID), disseminated gonococcal infection (DGI), and preterm labor. Treponema pallidum (syphilis) remains significant in certain populations despite declining overall incidence; primary infection presents with chancre, secondary with systemic manifestations, and tertiary/neurosyphilis develops untreated; maternal spirochetemia readily crosses placenta with 40-80% congenital transmission risk if untreated, increasing with advanced maternal disease. Group B streptococcus (Streptococcus agalactiae) colonizes 20-30% of pregnant women rectovaginally; while maternal infection is typically asymptomatic, ascending infection causes chorioamnionitis, and neonatal transmission during labor causes early-onset neonatal sepsis (EONS) in 1-2 per 1000 live births without intrapartum prophylaxis.

• Viral STIs: Herpes simplex virus types 1 and 2 establish latency in dorsal root ganglia with recurrent reactivation; pregnancy increases reactivation risk, and primary HSV during pregnancy carries substantial risk of disseminated maternal infection (10-30%) and neonatal transmission in 30-50% of vaginal deliveries. Human papillomavirus (HPV), especially high-risk types 16, 18, 31, and 33, causes genital warts and cervical dysplasia; while rarely causing vertical transmission, cervical lesions increase bleeding risk during delivery and rapidly enlarge during pregnancy. Human immunodeficiency virus (HIV) transmission to infants occurs through breast milk and intrapartum exposure; maternal viral load is the primary determinant of transmission risk (undetectable viral load <50 copies/mL reduces transmission to <2%), making virologic control essential. Cytomegalovirus (CMV) affects 0.5-1% of live births; primary maternal infection confers 30-40% risk of congenital transmission versus 1-2% with recurrent infection; congenital CMV is the leading infectious cause of congenital hearing loss and neurodevelopmental disability. Rubella, now rare in vaccinated populations, causes congenital rubella syndrome in 85-90% of infected fetuses during first trimester with cardiac, ocular, auditory, and neurologic manifestations; immunity can be confirmed serologically before conception.

• Parasitic infections: Toxoplasma gondii is transmitted via consumption of undercooked meat or contact with cat feces; congenital transmission occurs in 30-40% of pregnant women with acute infection, with severity inversely proportional to gestational age (congenital infection rates: 15% at 13 weeks, 24% at 20 weeks, 60% at 36 weeks, but severe manifestations predominate in early infection). Trichomonas vaginalis is the most common curable STI globally; while not directly teratogenic, it increases risk of preterm birth and low birth weight by 1.5-2 fold. Mycoplasma genitalium, an emerging pathogen, causes persistent urogenital infection and is associated with increased pregnancy complications including PROM and preterm birth; macrolide resistance is increasing, complicating treatment.

• Risk factors for STI acquisition and vertical transmission: Demographic factors include age <25 years, lower socioeconomic status, limited prenatal care, and racial/ethnic disparities in STI burden. Behavioral factors include multiple sexual partners, inconsistent barrier contraception, substance abuse (which impairs sexual decision-making), and partner STI status. Maternal immunosuppression—particularly CD4 count <200 cells/mm³ in HIV-positive women—dramatically increases risk of CMV dissemination, toxoplasmosis, and other opportunistic infections. Timing of infection critically determines vertical transmission risk: early pregnancy infection (especially first trimester for syphilis, CMV, and rubella) causes highest risk of congenital manifestations and organogenesis disruption, while third trimester infection increases acute maternal morbidity and neonatal transmission during delivery. Prior STI history, sexually transmitted co-infections, and cervicitis increase ascending infection risk, while intact membranes provide relative protection until rupture.

• Asymptomatic infection: The majority of pregnant women with chlamydia (70-80%), gonorrhea (50-60%), GBS (>95%), and trichomonas (50% of women) are asymptomatic, with infection detected only through screening; this underscores the critical importance of routine STI screening in pregnancy regardless of symptoms or perceived risk.

• Urogenital symptoms: Dysuria (burning on urination) and urinary frequency reflect inflammation of the urethra and bladder trigone from bacterial infection; gonorrhea and chlamydia cause acute dysuria with exudate production. Vaginal discharge varies by organism: gonorrhea produces thick, purulent, yellow-green discharge with offensive odor due to intense polymorphonuclear infiltration; chlamydia causes mucopurulent cervical discharge often accompanied by cervical friability; trichomonas produces copious, frothy, yellow-green discharge with characteristic fishy odor due to bacterial overgrowth and vaginal epithelial irritation. Urethritis may progress to Bartholin's gland abscess formation (particularly with gonorrhea), causing localized pain and swelling; pus expression from urethral meatus or Bartholin's duct supports diagnosis.

• Systemic symptoms of primary genital herpes: Painful vesicular lesions accompanied by fever, myalgias, and malaise develop 2-14 days after inoculation; severe pain during primary infection can impair ambulation and micturition, requiring analgesia and occasionally urinary catheterization. Inguinal lymphadenopathy develops 7-10 days post-lesion onset, reflecting local immune response. Systemic dissemination occurs in 10-30% of primary HSV during pregnancy, manifesting with hepatitis (elevated transaminases 5-10 fold), thrombocytopenia, disseminated intravascular coagulation (DIC), encephalitis (fever, altered mental status, seizures), and even fatal encephalitis; maternal mortality from disseminated HSV ranges 5-10% without treatment.

• Vaginal ulcerations and systemic signs of secondary syphilis: Primary syphilis presents with painless chancre at inoculation site (genitals, lips, or rectum); the ulcer is indurated, has a clean base, and drains clear serous fluid positive on darkfield microscopy. Secondary syphilis develops 3-12 weeks later with systemic manifestations including maculopapular rash (particularly on palms and soles—highly characteristic), condyloma lata (broad, flat lesions in warm, moist areas), mucous patches (gray-white lesions in oral cavity), generalized lymphadenopathy, fever, and hepatosplenomegaly. In pregnancy, secondary syphilis signals high treponemal burden with exponentially increased placental invasion risk; maternal untreated secondary syphilis carries 70-80% risk of fetal infection.

• Vaginal bleeding and preterm labor: Ascending chlamydial or gonococcal infection triggers endometrial and placental inflammation with prostaglandin production (PGE2, PGF2α), causing dysrhythmic uterine contractions and preterm labor; infection typically precedes labor onset by 1-2 weeks. Bloody vaginal discharge reflects endometrial inflammation and friability. Lower abdominal and pelvic pain from endometritis (fever, tachycardia, uterine tenderness) or salpingitis (unilateral adnexal pain, guarding) indicates ascending infection requiring urgent intervention.

• Genital warts and cervical lesions (HPV): Condyloma acuminata appear as papillary or sessile growths on external genitalia, perineum, and perianal skin; lesions rapidly enlarge during pregnancy due to altered immune tolerance and increased vascularization, sometimes reaching several centimeters. Cervical dysplasia may progress during pregnancy; severe dysplasia (CIN 2-3) increases risk of bleeding during delivery and potential for malignant transformation.

• Ocular and respiratory findings of neonatal chlamydia: Inclusion conjunctivitis presents at 5-14 days of age with eyelid edema, chemosis, and mucopurulent discharge from conjunctival inflammation; Gram stain reveals inclusion bodies in epithelial cells (pathognomonic), and untreated infection lasts weeks to months. Chlamydial pneumonia develops in 5-15% of exposed infants at 2-12 weeks of age with staccato cough (characteristic dry, paroxysmal cough), tachypnea, and hyperinflation on chest X-ray; wheezing is notably absent, and hypoxemia may be disproportionate to radiographic findings.

• Purulent conjunctivitis of neonatal gonorrhea (ophthalmia neonatorum): Presents at 2-5 days of life with dramatic purulent discharge, lid edema, chemosis, and conjunctival injection; progression to corneal involvement occurs within days if untreated, with corneal ulceration, scarring, and blindness in untreated cases.

• Disseminated neonatal herpes: Presents at 5-14 days of age with vesicles on skin/mucous membranes, fever, irritability,

Screening is the diagnostic entry point (CDC STI Treatment Guidelines, ACOG, USPSTF)

• First prenatal visit panel: HIV (opt-out), syphilis, hepatitis B surface antigen, and Chlamydia trachomatis NAAT (all women <25 years and older women at increased risk); gonorrhea NAAT by the same risk criteria. CDC and ACOG recommend repeat syphilis testing in the third trimester and again at delivery for at-risk populations, and many states now mandate universal three-time testing.
• Group B streptococcus: rectovaginal culture at 36 0/7–37 6/7 weeks (ACOG). GBS bacteriuria at any colony count during the pregnancy, or a prior infant with invasive GBS, obviates culture — treat intrapartum regardless.

Confirmatory testing by organism

• Syphilis: nontreponemal screen (*RPR*/*VDRL*) confirmed by a treponemal test (TP-PA, FTA-ABS), or the reverse-sequence algorithm (treponemal immunoassay first, then RPR, then TP-PA to adjudicate discordance). A fourfold (two-dilution) titer change defines treatment response or reinfection. High antibody burden in secondary syphilis and pregnancy can cause the prozone phenomenon — a false-negative RPR that becomes positive on dilution.
• Chlamydia/gonorrhea: NAAT on a vaginal or endocervical swab is both initial and gold-standard test; culture is reserved for gonococcal resistance testing. CDC advises a test of cure ~4 weeks after treatment in pregnancy plus retesting at 3 months.
• HSV: PCR of a swabbed lesion base is the test of choice; type-specific glycoprotein G serology distinguishes true primary from recurrent disease, which drives transmission risk. Tzanck smear is insensitive and obsolete.
• Trichomonas: NAAT, not saline wet mount — motile trichomonads are seen in only about half of infections.
• HIV: fourth-generation antigen/antibody immunoassay, then HIV-1/2 differentiation assay; HIV RNA if acute infection is suspected or the differentiation assay is indeterminate. Quantitative viral load near delivery determines the delivery plan.
• Congenital syphilis workup: darkfield or PCR of lesions/placenta, infant nontreponemal titer compared with maternal titer, long-bone radiographs (periostitis, metaphyseal lucency), and CSF VDRL/cell count.

First-line regimens (CDC STI Treatment Guidelines, 2021)

• Syphilis — benzathine penicillin G IM: the only acceptable therapy in pregnancy at every stage. A penicillin-allergic pregnant patient must undergo skin testing and desensitization, then receive penicillin. Doxycycline is contraindicated (fetal bone/teeth) and does not treat the fetus.
• Chlamydia — macrolide, azithromycin 1 g PO single dose: preferred in pregnancy because doxycycline, the nonpregnant first-line agent, is contraindicated. Amoxicillin is the alternative.
• Gonorrhea — third-generation cephalosporin, ceftriaxone 500 mg IM single dose (1 g if ≥150 kg), plus azithromycin only if chlamydia has not been excluded. Fluoroquinolones are avoided for resistance and fetal cartilage concerns. True cephalosporin cross-reactivity in penicillin allergy is about 1–3%, driven by shared R1 side chains — most patients can safely receive ceftriaxone; otherwise consult infectious diseases.
• Trichomoniasis — nitroimidazole, metronidazole (multi-day regimen for women); safe in all trimesters. Treat partners.
• Genital HSV — nucleoside analogue, acyclovir or valacyclovir: episodic treatment for outbreaks and suppression from 36 weeks to reduce lesions at labor (ACOG). Cesarean delivery is indicated for active genital lesions or prodromal symptoms at labor; HSV alone is not an indication for cesarean if no lesions.
• HIV — combination ART throughout pregnancy (HHS Perinatal Guidelines) targeting undetectable viral load. If viral load >1000 copies/mL near term: scheduled cesarean at 38 weeks plus intrapartum IV zidovudine, with infant antiretroviral prophylaxis.
• GBS — intrapartum IV penicillin G (ampicillin alternative). For low-risk penicillin allergy use cefazolin; for high-risk allergy, clindamycin only if the isolate is susceptible with negative inducible-resistance (D-test), otherwise vancomycin — dosed to a 24-hour AUC per the 2020 IDSA/ASHP consensus.
• Hepatitis B: antiviral (tenofovir) for high maternal viral load (AASLD); newborn receives HBIG plus vaccine within 12 hours.

Obstetric complications (ascending infection)

• Preterm labor and PPROM: cytokine- and prostaglandin-driven cervical ripening from chlamydia, gonorrhea, trichomonas, or bacterial vaginosis; signaled by contractions with cervical change or fluid pooling with positive nitrazine/ferning.
• Chorioamnionitis — an obstetric emergency: maternal fever with fetal tachycardia, fundal tenderness, or purulent fluid. Requires IV antibiotics and expedited delivery; sequelae include postpartum endometritis, sepsis, and fetal inflammatory response syndrome.
• Disseminated gonococcal infection: bacteremic spread causing the dermatitis–arthritis syndrome (pustular acral lesions, tenosynovitis, migratory polyarthralgia) — an emergency requiring IV ceftriaxone.

Fetal and neonatal complications

• Congenital syphilis: transplacental spirochetemia → hydrops fetalis, stillbirth, hepatosplenomegaly, snuffles, and periostitis/saber shins; late stigmata include Hutchinson teeth, interstitial keratitis, and CN VIII deafness. Any unexplained mid-to-late fetal demise should prompt maternal RPR.
• Neonatal HSV — emergency: SEM, CNS, or disseminated disease at 5–21 days; seizures or shock with transaminitis demand immediate high-dose IV acyclovir before confirmation.
• Ophthalmia neonatorum: gonococcal disease at 2–5 days can perforate the cornea within days — an ocular emergency treated with systemic ceftriaxone, not ointment alone. Erythromycin eye prophylaxis prevents gonococcal but not chlamydial conjunctivitis or chlamydial pneumonia.
• Early-onset GBS sepsis: respiratory distress and shock in the first 24–48 hours of life.
• Perinatal HIV and hepatitis B transmission: reduced to very low rates by maternal viral suppression and neonatal immunoprophylaxis, respectively.

Treatment-related complications

• Jarisch–Herxheimer reaction: cytokine surge after penicillin kills spirochetes — fever, myalgia, and, uniquely in pregnancy, uterine contractions and fetal heart rate decelerations. Treat with antipyretics and monitor the fetus; do not withhold penicillin.
• Anaphylaxis during penicillin desensitization: perform in a monitored setting with epinephrine 0.3 mg IM available.
• Metronidazole: disulfiram-like reaction with alcohol; metallic taste.
• Vancomycin: infusion reaction and nephrotoxicity; AUC-guided dosing limits the latter.

• Penicillin is non-negotiable for syphilis in pregnancy: the single best next step for a penicillin-allergic pregnant patient with syphilis is skin testing and desensitization, then benzathine penicillin G. Choosing doxycycline or azithromycin is the classic wrong answer — neither reliably treats the fetus.
• Prozone phenomenon: a negative RPR in a patient with florid secondary syphilis (palmar–plantar rash, condyloma lata) means antibody excess; the next step is dilution of the serum, not exclusion of syphilis.
• HSV cesarean rule: deliver by cesarean only for active lesions or prodromal symptoms in labor; a history of HSV with no lesions warrants vaginal delivery plus antiviral suppression started at 36 weeks. Neonatal risk is far higher with primary than recurrent maternal infection because transplacental antibody is absent.
• Two neonatal conjunctivitides, two timelines: gonococcal at 2–5 days with copious purulent discharge (corneal perforation risk); chlamydial at 5–14 days with mucopurulent discharge, later followed by staccato cough afebrile pneumonia with eosinophilia and no wheezing. Erythromycin ointment prophylaxis does not prevent the chlamydial forms.
• GBS is a colonization, not an infection: culture at 36 0/7–37 6/7 weeks; treat intrapartum with IV penicillin. GBS bacteriuria or a prior affected infant = prophylaxis without culture. Antenatal oral antibiotics do not eradicate colonization — a favorite distractor.
• Doxycycline swap: doxycycline is first-line for chlamydia in nonpregnant adults but is contraindicated in pregnancy; azithromycin replaces it. Similarly, podophyllin and imiquimod for warts are out — use cryotherapy or trichloroacetic acid.
• Fever and contractions hours after the first penicillin dose = Jarisch–Herxheimer, not drug allergy or chorioamnionitis. Monitor the fetus; continue therapy.
• The 10% cephalosporin cross-reactivity figure is historical; true risk is roughly 1–3% and side-chain driven, so ceftriaxone is usually safe for gonorrhea in penicillin-allergic pregnant patients.