Pregnancy, Childbirth & Puerperium

TORCH infections in pregnancy

Clinical Overview and When to Suspect TORCH Infections

— Toxoplasmosis

— Other: syphilis, varicella, parvovirus B19, listeria, HIV, HBV, Zika

— Rubella

— Cytomegalovirus (CMV)

— Herpes simplex virus (HSV)

— Maternal flu-like illness, lymphadenopathy, rash, or arthralgias in any trimester

— Exposure history: cats/litter box, undercooked meat (toxo); daycare/toddlers (CMV, parvovirus); unvaccinated contacts (rubella, varicella); high-risk sexual exposure (syphilis, HIV, HSV); travel to Zika-endemic regions

— Abnormal fetal ultrasound: IUGR, microcephaly, ventriculomegaly, intracranial calcifications, hyperechoic bowel, hydrops, hepatosplenomegaly, placentomegaly

— Unexplained polyhydramnios or oligohydramnios with fetal anomalies

— Not routinely screened: toxoplasmosis, CMV, parvovirus (test only if clinically indicated)

TORCH = classic acronym for congenital infections crossing the placenta or acquired perinatally with shared features (IUGR, hepatosplenomegaly, rash, CNS findings, sensorineural hearing loss)

When to suspect in pregnancy:

Trimester matters: earlier maternal infection = higher risk of severe fetal malformation but lower vertical transmission rate (toxo, rubella, CMV); later infection = higher transmission but milder disease

Universal screening at first prenatal visit: HIV, syphilis (RPR/VDRL), HBV surface antigen, rubella IgG immunity, varicella history

Step 3 management: When a pregnant patient presents with mononucleosis-like illness + negative monospot, broaden differential to CMV, toxoplasmosis, acute HIV, and primary EBV — order CMV IgM/IgG with avidity, Toxoplasma IgM/IgG, and HIV RNA

Board pearl: Among TORCH infections in the US, CMV is the most common congenital infection (~0.5–1% of live births) and the leading infectious cause of congenital sensorineural hearing loss and non-genetic intellectual disability — yet it is not part of routine prenatal screening, making maternal exposure counseling (hand hygiene around toddlers) the primary prevention strategy

Presentation Patterns and Key History

— Toxoplasmosis: usually asymptomatic; ~10% have cervical lymphadenopathy, fatigue, low-grade fever mimicking mono. Ask about cat litter, gardening, undercooked lamb/pork, unwashed produce

— CMV: mono-like syndrome with fever, malaise, lymphadenopathy, mild transaminitis. Ask about young children at home, daycare, healthcare work

— Rubella: low-grade fever, postauricular/suboccipital lymphadenopathy, fine maculopapular rash starting on face, polyarthralgia (especially in adults). Ask vaccination status, recent travel

— Parvovirus B19: arthralgias in adults (the "slapped cheek" rash is mainly pediatric). Ask about school-aged children, teacher/daycare worker

— Varicella (VZV): pruritic vesicular rash in different stages; ask about chickenpox/vaccination history, recent exposure

— HSV: painful genital vesicles/ulcers; ask about prior outbreaks, partner history

— Syphilis: painless chancre (primary), diffuse rash including palms/soles + condyloma lata (secondary); often asymptomatic latent

— Zika: fever, conjunctivitis, arthralgia, maculopapular rash; travel to endemic area or sexual exposure to traveler within 8 weeks

— Microcephaly, hydrocephalus, chorioretinitis, cataracts, congenital heart defects, blueberry-muffin rash, sensorineural hearing loss, IUGR, hepatosplenomegaly

Maternal presentations are often subtle or asymptomatic; ask targeted exposure questions

Fetal/neonatal red flags prompting retrospective TORCH workup:

Key distinction: Primary maternal infection during pregnancy carries far higher fetal risk than reactivation/recurrence — critical for CMV (1° transmission 30–40% vs recurrent <2%) and HSV (1° genital infection near delivery ~50% vs recurrent ~3%)

Board pearl: A pregnant daycare worker with fever, arthralgias, and a child with "slapped cheek" rash should raise suspicion for parvovirus B19 → check IgM/IgG; if acute, plan serial fetal ultrasounds and middle cerebral artery (MCA) Doppler for 8–12 weeks to detect hydrops from fetal anemia

Physical Exam Findings and Fetal Assessment

— Vital signs: low-grade fever common in CMV, toxo, rubella; high fevers atypical

— Skin: maculopapular rash (rubella, parvovirus, syphilis secondary, Zika); vesicular (HSV, VZV); palm/sole rash → secondary syphilis until proven otherwise; chancre (1° syphilis)

— Lymph nodes: posterior cervical/suboccipital = rubella; generalized = CMV, HIV, syphilis; isolated cervical = toxo

— HEENT: conjunctivitis (Zika, measles), pharyngitis (CMV, EBV)

— Abdomen: mild hepatosplenomegaly possible with CMV, toxo, syphilis

— Pelvic: genital ulcers/vesicles (HSV, syphilis); cervical motion tenderness if concurrent STI

— Intracranial calcifications: periventricular (CMV), scattered/diffuse (toxoplasmosis)

— Microcephaly: Zika (severe, often with arthrogryposis), CMV, rubella

— Hydrops fetalis (non-immune): parvovirus B19, syphilis, CMV

— Cataracts + cardiac defects (PDA, pulmonary stenosis) + sensorineural deafness: congenital rubella triad

— Hyperechoic bowel, ventriculomegaly, hepatic calcifications: CMV, toxoplasmosis

— Limb hypoplasia, cicatricial skin lesions: congenital varicella syndrome

— Long bone abnormalities, hydrops, placentomegaly: congenital syphilis

Maternal exam is frequently nonspecific; document systematically:

Fetal ultrasound findings — pattern recognition is high-yield:

MCA peak systolic velocity (PSV) > 1.5 MoM = fetal anemia → think parvovirus B19

Step 3 management: When fetal ultrasound shows IUGR + intracranial calcifications + ventriculomegaly, the next step is maternal CMV and Toxoplasma serology plus referral to maternal-fetal medicine (MFM) for amniocentesis with PCR

Board pearl: Periventricular calcifications + microcephaly + sensorineural hearing loss = CMV until proven otherwise; diffuse intracranial calcifications + chorioretinitis + hydrocephalus = classic Toxoplasma triad (Sabin tetrad with seizures)

Diagnostic Workup — Initial Labs and Imaging

— HIV (4th-gen Ag/Ab), opt-out

— Syphilis: RPR or VDRL (nontreponemal) → confirm with FTA-ABS/TP-PA; many labs now use reverse algorithm (treponemal first)

— HBsAg; also HCV antibody (USPSTF universal)

— Rubella IgG for immunity status (do not vaccinate during pregnancy; vaccinate postpartum if non-immune)

— Varicella: history-based; serology if uncertain

— Repeat HIV and syphilis in third trimester (28–32 wk) and at delivery in high-prevalence areas; universal third-trimester syphilis rescreening now recommended by CDC

— Toxoplasma: IgM + IgG; positive IgM → IgG avidity testing (high avidity = infection >3–4 months ago, reassuring; low avidity = recent)

— CMV: IgM + IgG + avidity index; rising IgG titers on paired sera also support primary infection

— Parvovirus B19: IgM (acute) + IgG (past/immune); CBC if anemia suspected

— Rubella: IgM (acute), IgG (immunity); confirm IgM positives due to false positives

— HSV: type-specific glycoprotein G serology (HSV-1 vs HSV-2); PCR/culture of lesions

— Zika: NAAT (RNA) within 12 weeks of symptoms; IgM with confirmatory PRNT

— Detailed anatomy ultrasound at 18–22 weeks, then serial growth scans every 3–4 weeks if infection confirmed

— Fetal MRI as adjunct for CNS findings (especially CMV, Zika)

Routine first-prenatal-visit screen (US standard of care):

Targeted serology when clinically suspected — paired IgM and IgG:

Imaging:

CCS pearl: On the CCS, after positive CMV IgM in a pregnant patient, order CMV IgG avidity before sending for amniocentesis — low avidity supports primary infection and justifies invasive testing

Board pearl: Amniocentesis with PCR is the gold standard for fetal infection diagnosis; perform ≥21 weeks gestation AND ≥6–8 weeks after maternal infection to optimize sensitivity (fetal renal excretion of pathogen into amniotic fluid)

Diagnostic Workup — Advanced and Confirmatory Studies

— CMV PCR: sensitivity >90% if performed >21 weeks and >6–8 weeks post-maternal infection; quantitative viral load correlates with severity

— Toxoplasma PCR: amniotic fluid PCR for T. gondii DNA; high specificity

— Parvovirus B19 PCR if hydrops; Zika RNA NAAT in amniotic fluid (sensitivity limited)

— Risks: ~0.1–0.3% pregnancy loss, vertical transmission of HIV/HBV/HCV if maternal viremia — defer or treat first

— PSV >1.5 MoM → percutaneous umbilical blood sampling (PUBS) ± intrauterine transfusion

— CMV: urine or saliva PCR within first 21 days of life (after that cannot distinguish congenital from postnatal acquisition)

— Toxoplasma: neonatal IgM/IgA, persistent IgG beyond 12 months, PCR of CSF/blood

— Syphilis: nontreponemal titer ≥4× maternal, IgM FTA-ABS, dark-field of lesions, long-bone X-rays, LP for VDRL/cell count

— HSV: surface swabs (mouth, conjunctiva, nasopharynx, anus) + blood/CSF PCR at 24 hours of life if at-risk delivery

— Rubella: IgM, viral culture of nasopharynx/urine

— Zika: RNA NAAT (serum + urine) and IgM in first 2 days

— Traditional: nontreponemal (RPR) → confirm with treponemal

— Reverse: treponemal EIA → if positive, RPR for activity; if RPR negative, second treponemal test (TP-PA) to resolve

Amniocentesis with PCR — definitive for fetal infection:

Fetal MRI: superior to ultrasound for cortical malformations, polymicrogyria, white matter changes (CMV, Zika); typically 28–32 weeks

Middle cerebral artery (MCA) Doppler PSV: screen for fetal anemia weekly in confirmed parvovirus B19 for 8–12 weeks post-exposure

Neonatal confirmatory testing (when antenatal diagnosis missed):

Reverse vs traditional syphilis algorithm:

Key distinction: A positive treponemal test with negative RPR in pregnancy still warrants treatment if treatment history is unclear — never assume false positive without documentation

Step 3 management: Maternal primary CMV at 14 weeks → counsel, then amniocentesis at ≥21 weeks AND ≥6 weeks post-infection + serial US + fetal MRI at 28–32 weeks

Risk Stratification and Management Logic

— CMV: transmission 30–40% (1° infection); severe sequelae higher in 1st trimester

— Toxoplasmosis: transmission 10–15% (1st tri) → 60–90% (3rd tri); severity inverse to GA at infection

— Rubella: 1st trimester transmission ~80% with severe defects; >20 weeks minimal risk

— Parvovirus B19: ~30% transmission; fetal loss/hydrops risk highest <20 weeks

— Varicella: 0.4–2% congenital varicella syndrome if maternal infection <20 weeks; neonatal varicella if maternal rash within 5 days before to 2 days after delivery (mortality up to 30%)

— HSV: highest neonatal risk with primary infection in 3rd trimester (~50% transmission)

— Syphilis: transmission >60–80% if untreated; any trimester

— Zika: 5–15% congenital Zika syndrome

— Counsel on transmission and severity risks

— Refer to MFM

— Initiate maternal treatment when available to reduce transmission/severity

— Offer amniocentesis at appropriate window

— Serial ultrasound surveillance

— Discuss pregnancy options if severe anomalies confirmed (legal/ethical, see chunk 17)

Stratify by: (1) which pathogen, (2) gestational age at infection, (3) primary vs recurrent, (4) fetal infection confirmed vs suspected, (5) presence of ultrasound abnormalities

Transmission risk by trimester:

Decision tree once maternal infection confirmed:

CCS pearl: After confirming maternal toxoplasmosis, start spiramycin immediately while awaiting amnio results — do not delay; reduces vertical transmission ~50%

Board pearl: The single most important historical factor for risk stratification is gestational age at maternal infection — memorize the inverse relationship for toxoplasmosis (early infection = low transmission but severe disease; late infection = high transmission but mild)

Pharmacotherapy — First-Line Maternal Treatment

— <14 weeks or before confirmed fetal infection: spiramycin 1 g PO q8h (concentrates in placenta, ↓transmission; doesn't cross placenta well, so doesn't treat fetus)

— Confirmed fetal infection or ≥14 weeks: pyrimethamine + sulfadiazine + folinic acid (leucovorin) — crosses placenta, treats fetus; avoid pyrimethamine in 1st trimester (teratogenic)

— Primary/secondary/early latent: benzathine PCN G 2.4 million units IM × 1

— Late latent/unknown duration: 2.4 million units IM weekly × 3 doses

— Neurosyphilis: aqueous PCN G IV × 10–14 days

— Penicillin-allergic → desensitize and treat with penicillin (doxycycline contraindicated; erythromycin doesn't reliably cross placenta)

— Warn about Jarisch-Herxheimer reaction (fever, contractions) — monitor fetus

Toxoplasmosis:

Syphilis — penicillin G is the only acceptable treatment in pregnancy:

HIV: ART regardless of CD4/viral load; typically dolutegravir + tenofovir/emtricitabine (current preferred; earlier teratogenicity signal not confirmed); goal viral load <1000 at delivery to allow vaginal delivery

HSV: acyclovir or valacyclovir suppression from 36 weeks until delivery if any history of genital HSV; treat primary infection with acyclovir

Varicella exposure (non-immune): VariZIG within 10 days of exposure; if active maternal varicella → IV acyclovir; VZIG to neonate if maternal rash within 5 days before to 2 days after delivery

CMV: no proven antenatal therapy in routine practice; valacyclovir 8 g/day in primary maternal infection has emerging evidence (CHIP trial) to reduce transmission; hyperimmune globulin not proven beneficial

Parvovirus B19: supportive; intrauterine transfusion for hydrops

Zika: supportive only; avoid NSAIDs after 20 weeks

Board pearl: Penicillin allergy in a pregnant patient with syphilis = desensitize, do NOT substitute. Doxycycline is teratogenic; erythromycin/azithromycin do not reliably treat the fetus. This is a classic Step 3 question.

Procedures and Delivery Planning

— Performed ≥15 weeks (typically ≥21 weeks for TORCH PCR) with ≥6–8 week interval from maternal infection

— Defer in untreated maternal HIV (until VL suppressed), HBV with high viral load, HCV — vertical transmission risk

— Provide Rh immunoglobulin if Rh-negative

— Triggered by MCA PSV >1.5 MoM ± hydrops

— PUBS confirms anemia (Hgb <0.65 MoM); transfuse via umbilical vein

— Resolves hydrops in ~85% with normal long-term outcomes

— HSV: cesarean delivery if active genital lesions or prodromal symptoms at onset of labor; vaginal delivery acceptable if no lesions (suppression from 36 wk reduces shedding)

— HIV: scheduled C-section at 38 weeks if VL >1000 or unknown near delivery; vaginal acceptable if VL <1000; IV zidovudine intrapartum if VL >1000

— HBV: vaginal delivery acceptable; infant gets HBIG + HBV vaccine within 12 hours; consider maternal tenofovir in 3rd trimester if VL >200,000 IU/mL

— Varicella active at delivery: cannot prevent vertical transmission; delay delivery if possible; give neonate VZIG ± IV acyclovir

— Syphilis: treat ≥4 weeks before delivery for "adequate" maternal treatment; otherwise infant requires full evaluation/treatment

— Contraindicated: HIV (in US), active HSV on breast, untreated active TB, certain meds

— Allowed: CMV (preterm <32 wk caution), HBV (with infant prophylaxis), HCV (unless cracked/bleeding nipples), syphilis (if no breast lesions, after treatment)

Amniocentesis:

Intrauterine transfusion (IUT) for parvovirus B19 fetal anemia:

Delivery mode considerations:

Avoid invasive fetal monitoring (scalp electrode, fetal scalp sampling) in HSV, HIV, HCV — increases vertical transmission

Breastfeeding:

CCS pearl: Pregnant patient at 39 weeks with painful vesicles on the labia → order cesarean delivery immediately, type and screen, IV access, antibiotics per institutional protocol; do NOT attempt vaginal trial.

Special Populations — Renal/Hepatic Impairment and Co-infections

— Acyclovir/valacyclovir: renally cleared; reduce dose with CrCl <50; risk of crystalluria/AKI with rapid IV infusion → hydrate

— Tenofovir disoproxil fumarate (TDF): nephrotoxic, especially with proteinuria/preeclampsia overlap; consider TAF or alternatives if CKD; monitor Cr and phosphate

— Sulfadiazine (toxoplasmosis): crystalluria, alkalinize urine, hydrate; avoid in severe renal impairment

— Penicillin G: adjust IV doses if CrCl <30

— Pregnancy itself causes mild ALT changes; differentiate from HEV, HSV hepatitis (rare but fulminant), CMV hepatitis, intrahepatic cholestasis of pregnancy, HELLP, acute fatty liver

— HSV hepatitis in pregnancy: anicteric transaminitis with fever and absent or atypical rash — high mortality, treat empirically with IV acyclovir while awaiting PCR

— Active HBV with high VL: tenofovir in 3rd trimester to reduce perinatal transmission

— HIV + syphilis: higher rates of neurosyphilis; consider LP if any neurologic signs or RPR ≥1:32

— HIV + CMV/toxo: risk of severe maternal disease with low CD4; treat OIs per standard guidelines

— HIV + HBV/HCV: coordinate ART to cover both (tenofovir + emtricitabine covers HBV)

— Rifampin (if TB) decreases protease inhibitor and dolutegravir levels — switch DTG dosing or use efavirenz

— Antacids/iron supplements decrease dolutegravir absorption — separate by 2–6 hours

Renal impairment:

Hepatic impairment:

Co-infections:

Drug interactions in ART regimens during pregnancy:

Step 3 management: Pregnant patient with anicteric fulminant hepatitis (AST/ALT in thousands), fever, and vesicular rash → empirically start IV acyclovir for presumed disseminated HSV before PCR confirms — delay = maternal mortality up to 40%

Board pearl: Sulfadiazine + pyrimethamine require folinic acid (leucovorin), NOT folic acid, to prevent bone marrow suppression; folic acid would antagonize the antiparasitic effect

Special Populations — Neonates and Adolescent/Immigrant Mothers

— Congenital CMV: symptomatic → valganciclovir PO × 6 months improves hearing/neurodevelopment; obtain head US, ophthalmology exam, auditory brainstem response (ABR), baseline CBC, LFTs

— Congenital toxoplasmosis: pyrimethamine + sulfadiazine + leucovorin × 12 months, even if asymptomatic

— Congenital syphilis: aqueous penicillin G IV × 10 days if mother inadequately treated or signs of infection; full evaluation (LP, CBC, LFTs, long-bone X-rays, ophtho)

— Neonatal HSV: IV acyclovir 20 mg/kg q8h × 14 days (SEM) or 21 days (CNS/disseminated), then suppression × 6 months

— Congenital rubella: supportive; cardiology, ophthalmology, audiology referrals

— Congenital Zika: head ultrasound, ophthalmology, ABR at birth; serial neurodevelopmental follow-up

— HIV-exposed neonate: zidovudine ± additional ART based on maternal VL; HIV NAAT at birth, 1–2 mo, 4–6 mo

— Higher rates of untreated STIs; ensure repeat screening every trimester

— Confidentiality protections (state-specific) for STI testing/treatment

— Higher prevalence of rubella non-immunity (incomplete vaccination), chronic HBV, HIV, syphilis, TB, Zika (depending on origin)

— Consider Chagas disease screening in patients from endemic Latin America (T. cruzi, vertically transmitted)

— MMR and varicella — live vaccines, give postpartum before discharge; avoid pregnancy × 28 days; safe in breastfeeding

— Tdap every pregnancy at 27–36 weeks (pertussis protection)

Neonatal management of TORCH exposure (newborn nursery / NICU considerations):

Adolescent pregnant patients:

Immigrant or recently traveled patients:

Postpartum vaccination for non-immune mothers:

Board pearl: Asymptomatic congenital CMV with isolated SNHL still benefits from valganciclovir to preserve hearing — refer to pediatric ID promptly.

Step 3 management: Non-immune-to-rubella postpartum patient → administer MMR before hospital discharge; document counseling on avoiding pregnancy for 28 days.

Complications and Adverse Outcomes

— Spontaneous abortion / stillbirth: parvovirus, syphilis, CMV, listeria, Zika, varicella

— Preterm labor: any TORCH infection via inflammation

— HSV hepatitis: rare but high mortality; can progress to fulminant hepatic failure

— Disseminated varicella with pneumonia: pregnant women at 5× higher mortality risk

— Jarisch-Herxheimer reaction: after PCN for syphilis — fever, hypotension, uterine contractions, fetal distress; treat supportively

— CMV: SNHL (most common sequela), microcephaly, periventricular calcifications, chorioretinitis, developmental delay, seizures

— Toxoplasmosis: classic tetrad — chorioretinitis, hydrocephalus, diffuse intracranial calcifications, seizures; SNHL

— Rubella: cataracts, sensorineural deafness, congenital heart disease (PDA, peripheral PA stenosis), "blueberry muffin" rash, microcephaly

— Parvovirus B19: severe fetal anemia, hydrops fetalis, myocarditis, fetal death; survivors usually normal

— Varicella (congenital syndrome <20 wk): limb hypoplasia, cicatricial skin scarring, chorioretinitis, microcephaly

— Neonatal varicella (perinatal exposure): disseminated disease, pneumonitis, hepatitis, 20–30% mortality without treatment

— HSV: SEM (skin/eye/mouth) — best prognosis; CNS — seizures, encephalitis; disseminated — multiorgan failure, ~50% mortality

— Syphilis: stillbirth, hydrops, hepatosplenomegaly, snuffles, saddle nose, Hutchinson teeth, mulberry molars, saber shins, interstitial keratitis (late)

— Zika: severe microcephaly, brain calcifications, ocular anomalies, arthrogryposis

Maternal complications:

Fetal/neonatal complications by pathogen:

Long-term: behavioral and learning disabilities common across CMV, toxo, Zika even in initially "asymptomatic" neonates

Key distinction: Blueberry muffin rash (extramedullary hematopoiesis) is classically seen in congenital rubella and CMV — both cause it, but rubella is the boards' favorite trigger.

Board pearl: Hutchinson triad of late congenital syphilis = interstitial keratitis + sensorineural deafness + Hutchinson incisors (notched).

When to Escalate Care — MFM, ID, and Inpatient Triage

— Any confirmed primary maternal infection (CMV, toxo, parvovirus, rubella, Zika, varicella) during pregnancy

— Any abnormal fetal ultrasound finding suggestive of TORCH (calcifications, hydrops, microcephaly, IUGR + anomalies)

— Need for amniocentesis, fetal MRI, intrauterine transfusion

— Maternal HIV (co-management with HIV specialist), syphilis with neurologic signs or treatment failure, immunocompromised mother with opportunistic infection, complex co-infections

— Before delivery if congenital infection confirmed or strongly suspected — allows planning for neonatal evaluation, isolation, treatment

— Disseminated varicella, varicella pneumonia → IV acyclovir

— Suspected HSV hepatitis or encephalitis → IV acyclovir

— Severe maternal toxoplasmosis with end-organ involvement (rare, usually immunocompromised)

— Jarisch-Herxheimer with fetal distress → continuous fetal monitoring

— Active genital HSV with rupture of membranes or labor onset → admit for C-section planning

— Suspected congenital syphilis in neonate → admit for IV PCN

— Maternal sepsis from listeria, disseminated HSV, varicella pneumonia with respiratory failure

— Pregnant patients have lower physiologic reserve: deteriorate quickly with pneumonia and sepsis

— Hand-off between OB and pediatrics critical for at-risk neonate — ensure newborn nursery receives maternal infection status in delivery summary

Refer to Maternal-Fetal Medicine (MFM):

Refer to Infectious Disease:

Refer to Pediatric ID and Neonatology:

Inpatient admission criteria:

ICU triage:

Transitions of care:

CCS pearl: Pregnant patient with disseminated vesicular rash + cough + hypoxia → admit to ICU, isolate (airborne + contact), start IV acyclovir 10 mg/kg q8h, OB and ID consults, continuous fetal monitoring.

Board pearl: Neonate born to mother with untreated or inadequately treated syphilis must always be evaluated — outpatient management is insufficient; admit for full work-up and PCN.

Key Differentials — Other Infections That Mimic TORCH

— EBV (mononucleosis): heterophile-positive, atypical lymphocytes, posterior cervical LAD, exudative pharyngitis; does not cause classic congenital syndrome but can be confused with CMV

— Acute HIV seroconversion: mono-like illness; HIV RNA positive, antibody may be negative early; always include in fever + rash + LAD differential in pregnancy

— Listeria monocytogenes: gastroenteritis or febrile illness in pregnant patient → can cause chorioamnionitis, preterm labor, stillbirth, neonatal sepsis/meningitis; ampicillin treatment

— Group B Streptococcus: vertically transmitted at delivery; universal screen 36–37+6 weeks; intrapartum ampicillin/penicillin

— Tuberculosis: congenital TB rare but possible; screen high-risk patients

— Chagas disease: T. cruzi in immigrants from Latin America; transplacental

— Malaria: placental malaria → IUGR, preterm birth, stillbirth in endemic regions

— Lymphocytic choriomeningitis virus (LCMV): rodent exposure; mimics congenital toxo with chorioretinitis and hydrocephalus

Within the infectious category — clinical pictures overlap; distinguishing features:

Influenza: high maternal mortality, treat with oseltamivir regardless of trimester; vaccinate all pregnant patients

SARS-CoV-2: increased risk of preterm birth, stillbirth, severe maternal disease; vaccinate

Measles, mumps: rare in vaccinated populations; measles increases miscarriage/preterm birth

Key distinction: CMV vs EBV in pregnancy — both cause heterophile-negative mononucleosis; CMV is far more relevant for fetal outcome. Test for CMV serology in any heterophile-negative mono in pregnancy.

Board pearl: Pregnant patient with febrile gastroenteritis after soft cheese or deli meat = listeriosis until proven otherwise → blood cultures, empiric ampicillin (add gentamicin if severe); do not wait for confirmation due to fetal risk.

Key Differentials — Non-Infectious Mimics

— Genetic/chromosomal: aneuploidies (trisomies 13, 18, 21) cause IUGR, brain anomalies, cardiac defects, calcifications

— Single-gene syndromes: microcephaly syndromes, Aicardi-Goutières (mimics congenital CMV with intracranial calcifications and CSF lymphocytosis), pseudo-TORCH syndromes

— Maternal autoimmune disease: neonatal lupus (anti-Ro/SSA, anti-La/SSB) → congenital heart block, cutaneous lupus rash, transaminitis — can mimic CMV/rubella

— Antiphospholipid syndrome: recurrent pregnancy loss, IUGR, placental insufficiency

— Maternal substance use: alcohol (FAS — microcephaly, smooth philtrum), cocaine (placental abruption, IUGR), opioids (NAS in neonate)

— Teratogens: warfarin (chondrodysplasia punctata, mimicking varicella), isotretinoin, valproate, methotrexate

— Radiation exposure in early pregnancy

— Uncontrolled diabetes: macrosomia or IUGR, congenital heart disease, caudal regression

— Phenylketonuria (maternal): microcephaly, intellectual disability if untreated

— Hypoxia/placental insufficiency: symmetric vs asymmetric IUGR

— SLE flare, adult-onset Still's disease, drug reaction (DRESS), erythema multiforme, dermatomyositis

— Immune (Rh, Kell alloimmunization), cardiac (arrhythmia, structural), chromosomal (Turner, trisomy 21), thoracic masses, twin-twin transfusion, metabolic (lysosomal storage diseases)

Non-infectious causes of fetal ultrasound findings mimicking TORCH:

Non-infectious causes of maternal rash + arthralgia + fever:

Hydrops fetalis non-infectious causes:

Key distinction: Aicardi-Goutières syndrome = the "pseudo-TORCH" — intracranial calcifications, leukoencephalopathy, CSF lymphocytosis, elevated interferon; negative TORCH serology should prompt genetic evaluation.

Board pearl: Congenital heart block + transient rash in neonate with negative TORCH workup → check maternal anti-Ro/SSA antibodies — neonatal lupus.

Secondary Prevention and Postpartum Plan

— MMR (rubella) — live attenuated; safe in breastfeeding; avoid pregnancy × 28 days

— Varicella — live attenuated; same precautions

— Tdap in every pregnancy (27–36 weeks) — already given antepartum

— Influenza any trimester or postpartum

— HBV for non-immune mothers

— COVID-19 boosters per current recommendations

— CMV: hand hygiene around toddlers, avoid sharing utensils/food, avoid kissing on the mouth, gloves during diaper changes

— Toxoplasmosis: avoid undercooked meat, wash produce, gloves when gardening, have someone else change cat litter or wash hands thoroughly

— Listeria: avoid soft unpasteurized cheeses, deli meats unless reheated, raw fish, unpasteurized dairy

— Zika/travel: avoid travel to endemic areas during pregnancy; condoms × 3 months (male partner) after travel

— STIs: condom use, partner treatment, repeat screening

— HIV: continue ART postpartum for maternal health

— HBV: continue antivirals if indicated; monitor for ALT flare after delivery

— Syphilis: follow nontreponemal titers every 3 months × 1 year; expect 4-fold decline

— HSV: discuss episodic vs suppressive therapy long-term

Postpartum vaccination for non-immune mothers (before hospital discharge):

Counseling on prevention for future pregnancies:

Treatment continuation:

Partner notification and treatment for STIs (mandatory reporting for syphilis, HIV, others — state-dependent)

Contraception counseling: timing of next pregnancy, especially after live vaccine (28 days)

Step 3 management: Postpartum visit at 3–6 weeks for STI rescreen, contraception, mood screen (EPDS), breastfeeding support, immunization confirmation, and partner treatment verification for any STI diagnosed during pregnancy.

Board pearl: Rubella-non-immune postpartum patient who breastfeeds can still receive MMR — live vaccines (except smallpox/yellow fever in some cases) are compatible with breastfeeding.

Follow-Up, Monitoring, and Counseling

— Syphilis: RPR titers at 6 and 12 months (and 24 months for late latent); 4-fold decline = treatment success; rising titers = re-infection or treatment failure → LP and re-treat

— HIV: VL every 4–8 weeks during pregnancy, at 34–36 weeks for delivery planning; CD4 q3–6 months

— HBV: ALT and HBV DNA postpartum; watch for flare in 3–6 months

— Confirmed congenital infection: serial growth ultrasounds q3–4 weeks; fetal MRI at 28–32 wk; biophysical profile in 3rd trimester

— Neonatal CMV: ABR hearing screen at birth, q6 months until age 3, then annually until school age (progressive SNHL)

— Neonatal toxoplasmosis: ophthalmology q3 months × 1 year then yearly; neurodevelopmental assessments

— Neonatal HIV-exposed: NAAT at birth, 1–2 months, 4–6 months; HIV antibody at 18–24 months for definitive seroreversion

— Congenital syphilis: RPR q3 months until non-reactive; long-term ophtho, audiology, neurology follow-up

— CMV: even "asymptomatic" infants need long-term hearing surveillance — up to 15% develop late-onset SNHL

— Zika: developmental milestones, neuroimaging at 12 months if abnormal at birth

— Psychological support: TORCH diagnoses cause significant maternal anxiety, guilt; offer counseling and support resources

— Genetic counseling if differential includes pseudo-TORCH or chromosomal etiology

— Early intervention services (Part C, US) for any neonate with confirmed congenital infection — speech, OT, PT, audiology, vision

Maternal monitoring after treatment:

Fetal/neonatal surveillance:

Counseling points:

Rehabilitation:

Board pearl: Congenital CMV requires lifelong hearing follow-up because hearing loss can be progressive or late-onset, even in infants with normal newborn hearing screens.

Step 3 management: At each postpartum follow-up for treated syphilis, document RPR titer trajectory — failure to decline 4-fold by 6–12 months warrants LP and retreatment.

Ethical, Legal, and Patient Safety Considerations

— Discuss procedure risks (pregnancy loss ~0.1–0.3%), benefits, alternatives, and implications of results including option to continue or terminate pregnancy

— Document patient-centered decision; respect autonomy regardless of test choice

— HIV-positive mother: ensure VL suppressed before amnio to minimize vertical transmission

— Syphilis, HIV, gonorrhea, chlamydia, hepatitis B, congenital syphilis, congenital rubella — reportable to local/state health departments

— Partner notification services available through health departments; patient consent typically required but expedited partner therapy (EPT) allowed in many states for chlamydia/gonorrhea

— Universal opt-out screening at first prenatal visit and in 3rd trimester for high-risk; verbal documentation; patients may decline but counseling required

— Counseling regarding severe congenital infection findings (e.g., severe Zika microcephaly, advanced CMV) must be non-directive, present all options, comply with state-specific gestational age limits (post-Dobbs landscape varies dramatically by state — know your state's law)

— Adolescents: state law governs whether minors can consent to STI testing/treatment without parental notification

— Domestic violence screening at intake — STI/HIV diagnosis may trigger safety concerns

— Maternal infection status MUST be communicated to delivery team, NICU, pediatrician — written handoff prevents missed neonatal evaluations (e.g., missing CMV PCR within 21 days loses ability to diagnose congenital CMV)

— Closed-loop communication on culture results pending at discharge — system to follow up positive HSV, GBS, syphilis results post-discharge

Informed consent for amniocentesis:

Mandatory reporting (state-specific but largely universal in US):

HIV testing — opt-out consent:

Pregnancy termination:

Confidentiality:

Patient safety / transitions of care:

Vaccination ethics: respect patient autonomy regarding postpartum MMR/varicella; document refusal and counsel about future pregnancy risks

Step 3 management: A patient declines HIV testing at first prenatal visit → document counseling, do not coerce, revisit at subsequent visits, and continue routine prenatal care. Re-offer in third trimester.

Board pearl: Failure to obtain neonatal CMV PCR within the first 21 days of life is a common safety lapse — establish a system-level checklist.

High-Yield Associations and Rapid-Fire Facts

— Periventricular calcifications + microcephaly + SNHL → CMV

— Diffuse scattered intracranial calcifications + chorioretinitis + hydrocephalus → toxoplasmosis

— Cataracts + PDA + sensorineural deafness → congenital rubella

— Hydrops + "slapped cheek" exposure → parvovirus B19

— Limb hypoplasia + cicatricial skin scarring → congenital varicella

— Vesicles on scalp + neonatal seizures → neonatal HSV

— Snuffles + saddle nose + saber shins → congenital syphilis

— Severe microcephaly + arthrogryposis + travel history → Zika

— Blueberry muffin rash → rubella or CMV

— Neonatal heart block (negative TORCH) → neonatal lupus (anti-Ro)

— Cat litter, undercooked meat → toxo

— Toddlers/daycare → CMV, parvovirus

— Soft cheese, deli meat → listeria

— Travel to tropics → Zika, malaria

— Spiramycin → toxo before fetal infection

— Pyrimethamine + sulfadiazine + leucovorin → toxo with fetal infection (after 1st trimester)

— Benzathine PCN G → syphilis (any trimester)

— Acyclovir → HSV, VZV

— Valganciclovir → neonatal CMV

— VariZIG → varicella post-exposure prophylaxis

— Zidovudine → HIV intrapartum if VL >1000

— Early infection = worse fetal disease (toxo, rubella, varicella, Zika)

— Late infection = higher transmission (toxo, HSV, syphilis)

Classic image/finding → diagnosis:

Mnemonic: TORCH-Z for modern era including Zika

Highest-risk maternal exposures:

Drug-pathogen pairings:

Universal first-visit screen: HIV, syphilis, HBsAg, HCV, rubella IgG, varicella, GC/CT, urine culture

Not routinely screened: CMV, toxo, parvovirus, HSV (history only)

Trimester rule of thumb:

Board pearl: Penicillin allergy + syphilis + pregnancy = desensitize. There is no acceptable alternative. This appears on virtually every iteration of Step 3.

Key distinction: CMV calcifications periventricular; toxoplasmosis calcifications scattered/diffuse.

Board Question Stem Patterns

— Best next step: parvovirus B19 IgM and IgG; if acute → serial MCA Doppler q1–2 weeks × 8–12 weeks for fetal anemia.

— Toxoplasma IgM/IgG with IgG avidity; if acute → spiramycin until amniocentesis at ≥21 weeks.

— RPR positive, confirm with FTA → benzathine PCN G IM; if PCN allergic → desensitize.

— Cesarean delivery.

— Test for CMV IgM/IgG with avidity (and toxo, HIV).

— Maternal CMV serology + MFM referral + amniocentesis at ≥21 weeks.

— Administer MMR before discharge, avoid pregnancy × 28 days; safe with breastfeeding.

— VariZIG within 10 days of exposure.

— Vaginal delivery acceptable; continue ART; neonate gets zidovudine.

— Test for parvovirus B19, syphilis, CMV; obtain placental pathology and fetal autopsy.

Stem 1 — Daycare worker: "26-year-old pregnant teacher at 18 weeks presents with arthralgias and low-grade fever. Her 6-year-old students had a 'slapped cheek' rash last week."

Stem 2 — Cat owner: "29-year-old G1P0 at 14 weeks has cervical lymphadenopathy and fatigue. She has two indoor cats and gardens regularly."

Stem 3 — Rash in palms/soles: "Pregnant patient at 24 weeks with maculopapular rash on trunk, palms, and soles, condyloma lata, prior negative prenatal labs."

Stem 4 — Active genital lesions in labor: "G2P1 at 39 weeks in active labor with painful vulvar vesicles."

Stem 5 — Heterophile-negative mono in pregnancy: "Pregnant woman with fatigue, lymphadenopathy, mild transaminitis, negative monospot."

Stem 6 — Ultrasound calcifications: "20-week anatomy scan shows periventricular calcifications, ventriculomegaly, IUGR."

Stem 7 — Postpartum vaccination: "Patient was rubella non-immune throughout pregnancy."

Stem 8 — Varicella exposure in non-immune pregnant patient:

Stem 9 — HIV-positive mother, VL <50 at 38 weeks:

Stem 10 — Stillbirth at 22 weeks with hydrops, no Rh issue:

CCS pearl: On CCS, after diagnosing maternal syphilis, (1) treat with PCN, (2) repeat RPR titers, (3) notify partner, (4) report to health department, (5) schedule neonatal evaluation — all are scored actions.

One-Line Recap

TORCH infections — toxoplasmosis, "other" (syphilis, parvovirus, varicella, HIV, listeria, Zika), rubella, CMV, and HSV — are vertically transmitted maternal infections whose fetal risk depends on gestational age and primary vs recurrent status, and whose management hinges on routine first-visit screening, targeted serology when clinically suspected, MFM-coordinated amniocentesis/ultrasound surveillance, pathogen-specific maternal therapy, and meticulous neonatal handoff.

Universally screen at first prenatal visit: HIV, syphilis, HBV, HCV, rubella immunity, varicella history; rescreen syphilis and HIV in 3rd trimester

CMV = most common congenital infection in the US and leading non-genetic cause of SNHL; prevent through hygiene counseling, not screening

Pencillin is the only acceptable treatment for syphilis in pregnancy — desensitize if allergic; never substitute doxycycline or erythromycin

Trimester rule: early maternal infection → worse fetal disease but lower transmission; late infection → higher transmission but milder disease (with critical exceptions: HSV worst in 3rd trimester, varicella perinatal exposure devastating)

Amniocentesis with PCR is the gold-standard fetal diagnostic, performed at ≥21 weeks AND ≥6–8 weeks after maternal infection

Neonatal CMV PCR must be obtained within the first 21 days of life — a key transition-of-care checkpoint

Postpartum: vaccinate non-immune mothers (MMR, varicella) before discharge; continue ART for HIV; track syphilis RPR titers for 12 months

Board pearl: When in doubt on Step 3, the right move is MFM consultation, pathogen-specific serology with IgG avidity, and pre-delivery coordination with neonatology — these high-yield management steps repeatedly score points on vignettes and CCS.