Residency · Residency · Obstetrics Gynecology

Infections in Pregnancy: TORCH and Beyond

Overview

The TORCH acronym encompasses the major infections with potential for vertical transmission and fetal harm: Toxoplasmosis, Other (syphilis, varicella, parvovirus), Rubella, Cytomegalovirus, and Herpes simplex. Vertical transmission can occur transplacentally, during delivery, or postnatally. The timing of maternal infection determines the type and severity of fetal effects, and many of these infections are preventable through screening, vaccination, and behavioral precautions.

Cytomegalovirus (CMV)

Epidemiology

CMV is the most common congenital infection worldwide, affecting 0.5 to 1% of all live births. Seroprevalence among reproductive-age women in the United States is 50 to 80%. Primary infection occurs in 1 to 4% of seronegative women during pregnancy, with a transmission rate of approximately 30 to 40% in primary infection compared to only 1 to 3% with recurrent infection or reactivation.

Fetal Effects

Only 10 to 15% of congenitally infected neonates are symptomatic at birth. Symptomatic disease includes intrauterine growth restriction, microcephaly, periventricular calcifications, ventriculomegaly, hepatosplenomegaly, petechiae or purpura (blueberry muffin rash), chorioretinitis, and sensorineural hearing loss. Importantly, 90% of late sequelae, including hearing loss and cognitive impairment, occur in infants who were initially asymptomatic. First trimester primary infection produces the most severe fetal effects.

Diagnosis

Maternal diagnosis relies on CMV IgG and IgM testing, with IgG avidity testing to distinguish recent from remote infection (low avidity suggests recent primary infection). Fetal diagnosis requires amniocentesis for CMV PCR in amniotic fluid, which should be performed at or after 21 weeks and at least 6 weeks after maternal seroconversion. Ultrasound findings suggestive of congenital CMV include microcephaly, ventriculomegaly, periventricular calcifications, echogenic bowel, growth restriction, and hydrops.

Management

Universal prenatal screening for CMV is not currently recommended by ACOG. Prevention focuses on hand hygiene and avoiding sharing utensils with young children, who are the primary source of exposure. Valacyclovir at 8 g per day may reduce transmission if started after primary infection, though this is based on emerging data and is not yet standard of care. When a severely affected fetus is identified, counseling about prognosis is provided, and termination may be discussed. Neonatal valganciclovir is used for symptomatic congenital CMV.

Toxoplasmosis

Epidemiology

Toxoplasmosis is caused by Toxoplasma gondii, an intracellular protozoan. Seroprevalence among US women is 10 to 15%. Sources of infection include undercooked meat, contaminated soil or water, and cat feces containing oocysts. The congenital infection rate increases with gestational age, rising from 10 to 15% in the first trimester to 60 to 80% in the third trimester. However, the severity of fetal disease is inversely related to gestational age at infection.

Fetal Effects

First trimester infection causes the most severe effects, including hydrocephalus, intracranial calcifications (diffuse in distribution, unlike the periventricular pattern seen in CMV), chorioretinitis, and seizures. Later infection is often subclinical at birth but carries risk of later chorioretinitis and neurodevelopmental problems.

Diagnosis

Maternal diagnosis involves Toxoplasma IgG and IgM testing, with positive IgM results confirmed at a reference laboratory due to the high false-positive rate. IgG avidity testing is helpful because high avidity excludes recent infection. Fetal diagnosis is made by amniocentesis for Toxoplasma PCR after 18 weeks.

Management

Spiramycin is started after maternal seroconversion to reduce maternal-fetal transmission, though it may not prevent established fetal infection. If fetal infection is confirmed, treatment with pyrimethamine, sulfadiazine, and folinic acid is initiated after the first trimester. Prevention centers on cooking meat thoroughly, washing produce, avoiding cat litter, and gardening with gloves.

Rubella

Epidemiology

Rubella has been largely eliminated in developed countries through MMR vaccination. Congenital rubella syndrome (CRS) still occurs in unvaccinated populations. Maternal rubella immunity is checked at the first prenatal visit.

Fetal Effects (Congenital Rubella Syndrome)

The first trimester carries the highest risk, with up to 80 to 90% vertical transmission and 85% of those developing CRS. The classic triad consists of sensorineural deafness, cataracts or glaucoma, and congenital heart defects (patent ductus arteriosus and pulmonary stenosis). Other manifestations include growth restriction, thrombocytopenia, blueberry muffin rash, hepatosplenomegaly, and intellectual disability. After 20 weeks, CRS is rare.

Management

Rubella IgG is checked at the first prenatal visit. Non-immune women are vaccinated postpartum, as MMR is a live vaccine and contraindicated in pregnancy. No effective treatment exists during pregnancy. Non-immune pregnant women exposed to rubella may receive immune globulin, which may reduce but not eliminate the risk.

Syphilis

Epidemiology

Congenital syphilis rates are rising dramatically in the United States. The causative organism is Treponema pallidum. Vertical transmission rates are 60 to 100% in primary and secondary syphilis, with lower rates in latent and tertiary disease.

Screening

Universal screening with RPR or VDRL is performed at the first prenatal visit. Repeat screening in the third trimester (28 to 32 weeks) and at delivery is recommended in high-risk populations. A positive non-treponemal test is confirmed with a treponemal test (FTA-ABS or TP-PA).

Fetal Effects

Congenital syphilis can cause hydrops fetalis, hepatosplenomegaly, growth restriction, and bone abnormalities. Early congenital syphilis (before 2 years) presents with snuffles (bloody rhinitis), maculopapular rash, condylomata lata, hepatitis, and anemia. Late congenital syphilis (after 2 years) is characterized by Hutchinson teeth, interstitial keratitis, saber shins, saddle nose, and frontal bossing.

Treatment

Penicillin G is the only adequate treatment for syphilis in pregnancy. For primary, secondary, and early latent disease, benzathine penicillin G 2.4 million units IM is given as a single dose. For late latent disease or disease of unknown duration, benzathine penicillin G 2.4 million units IM is given weekly for 3 weeks. Penicillin-allergic patients must be desensitized because no alternative antibiotic is adequate for fetal treatment. The Jarisch-Herxheimer reaction, consisting of fever and contractions, may occur within 24 hours of treatment and is managed with supportive care. Treatment response is monitored with serial RPR titers, with a 4-fold decline expected.

<image>Timeline showing the stages of syphilis in pregnancy with corresponding vertical transmission rates, fetal effects, and recommended penicillin treatment regimens for each stage (primary, secondary, early latent, late latent)</image>

Herpes Simplex Virus (HSV)

Epidemiology

HSV-2 seroprevalence among reproductive-age women in the United States is approximately 15 to 20%. Most genital herpes in pregnancy is due to HSV-2, though HSV-1 genital infections are increasing. Neonatal herpes occurs in approximately 1 in 3,000 to 20,000 live births.

Neonatal Transmission Risk

The risk of neonatal transmission depends heavily on whether the maternal infection is primary or recurrent at the time of delivery. A primary outbreak at delivery carries a 30 to 50% transmission risk, which is the highest-risk scenario. A recurrent outbreak at delivery carries approximately 2 to 3% risk. When no active lesions are present at delivery in a seropositive woman, the risk falls below 1%.

Management

Suppressive antiviral therapy with acyclovir 400 mg orally three times daily or valacyclovir 500 mg twice daily is started at 36 weeks for all women with a history of genital herpes. This reduces the rate of recurrence at delivery by approximately 75%. When active genital lesions or prodromal symptoms are present at the onset of labor, cesarean delivery is recommended regardless of membrane status. When no active lesions are present, vaginal delivery proceeds, with avoidance of unnecessary fetal scalp electrodes and operative vaginal delivery if possible. Primary HSV acquired in the third trimester represents the highest-risk situation, and cesarean delivery is recommended at the onset of labor for any woman with primary HSV within 6 weeks of delivery.

Hepatitis B

Screening

HBsAg is checked at the first prenatal visit as part of universal screening. If positive, HBeAg, HBV DNA viral load, and liver function tests are obtained.

Vertical Transmission Prevention

Vertical transmission prevention relies on neonatal hepatitis B immune globulin (HBIG) combined with HBV vaccine administered within 12 hours of birth. This combination reduces transmission from 90% to less than 5%. Maternal antiviral therapy with tenofovir is recommended when the viral load exceeds 200,000 IU/mL, starting at 28 to 32 weeks, to further reduce transmission risk. Breastfeeding is safe if the infant has received HBIG and vaccine.

Hepatitis C

Screening

Universal screening of all pregnant patients is now recommended by ACOG, the CDC, and the AASLD. Anti-HCV antibody testing is performed, with confirmation by HCV RNA if positive.

Management

Direct-acting antivirals (DAAs) are not yet approved for use in pregnancy, though clinical trials are underway. The vertical transmission rate is approximately 5 to 6%, higher with HIV coinfection. Cesarean delivery is not specifically recommended for hepatitis C alone. Prolonged rupture of membranes and internal fetal monitoring should be avoided if possible, though evidence for these precautions is limited. Breastfeeding is safe unless nipples are cracked or bleeding.

HIV

Screening

Opt-out universal screening is performed at the first prenatal visit, with repeat testing in the third trimester in high-risk populations.

Management

Combination antiretroviral therapy (cART) is continued if the patient is already on treatment and initiated as soon as possible if newly diagnosed. The goal is to achieve an undetectable viral load (below 1,000 copies/mL) by delivery. When the viral load is below 1,000 copies/mL at delivery, vaginal delivery is appropriate. When the viral load is 1,000 copies/mL or greater, a scheduled cesarean at 38 weeks with intrapartum IV zidovudine is recommended. Neonatal prophylaxis consists of zidovudine for 4 to 6 weeks, with additional agents added if the maternal viral load is high. ACOG now supports shared decision-making for breastfeeding in patients with sustained undetectable viral load on cART (updated 2023). Invasive procedures such as amniocentesis and fetal scalp electrodes should be avoided when the viral load is elevated.

Parvovirus B19 (Fifth Disease)

Epidemiology

Fifty to 60% of reproductive-age women are immune to parvovirus B19. Transmission occurs via respiratory droplets, with outbreaks commonly occurring in schools. The fetal infection rate is approximately 30% when maternal infection occurs during pregnancy.

Fetal Effects

Parvovirus B19 targets fetal erythroid progenitor cells, causing fetal anemia, hydrops fetalis, and potentially fetal death. The highest risk period is the second trimester, particularly around 18 to 20 weeks. Importantly, parvovirus does not cause congenital anomalies.

Diagnosis and Management

Maternal diagnosis relies on parvovirus IgG and IgM testing. If IgM is positive, serial ultrasound for hydrops and MCA Doppler for fetal anemia are performed weekly for 12 weeks. A hydropic fetus is treated with intrauterine transfusion, which achieves a survival rate of 70 to 80%. The infection is self-limited, and no antiviral treatment is available.

<image>Ultrasound image of fetal hydrops secondary to parvovirus B19 infection, showing ascites, pleural effusion, and skin edema, with a corresponding MCA Doppler waveform demonstrating elevated peak systolic velocity indicating severe fetal anemia</image>

Varicella-Zoster Virus (VZV)

Epidemiology

Ninety to 95% of reproductive-age women are immune to varicella through childhood infection or vaccination. Primary varicella occurs in approximately 0.5 to 3 per 1,000 pregnancies.

Maternal Risks

Varicella pneumonia is life-threatening and more severe in pregnancy, with mortality rates reaching 40% if untreated. Treatment consists of IV acyclovir for varicella pneumonia and oral acyclovir or valacyclovir for uncomplicated varicella.

Fetal Effects

Congenital varicella syndrome occurs with infection before 20 weeks and includes limb hypoplasia, skin scarring, cataracts, and central nervous system abnormalities, though the risk is only approximately 1 to 2%. Peripartum varicella, defined as maternal infection from 5 days before to 2 days after delivery, causes neonatal varicella with mortality up to 30%, and varicella-zoster immune globulin (VZIG) should be administered to the neonate.

Management

Varicella immunity should be checked at the first prenatal visit if status is unknown. Non-immune women who are exposed should receive VZIG within 10 days of exposure, ideally within 96 hours. Postpartum vaccination is recommended for non-immune women, as the varicella vaccine is a live vaccine and contraindicated in pregnancy.

Summary of Key Infections

Clinical Pearls

CMV is the most common congenital infection worldwide. Routine screening is not recommended, but awareness is critical, and patients should be counseled about hand hygiene around young children.

Congenital syphilis is preventable with penicillin. No alternative antibiotic is acceptable in pregnancy, and allergic patients must be desensitized.

Rising congenital syphilis rates make third-trimester rescreening essential in high-risk populations.

HSV suppressive therapy from 36 weeks reduces recurrence at delivery. Cesarean delivery is indicated only for active lesions or prodromal symptoms.

Parvovirus B19 causes fetal anemia, not anomalies. It is monitored with MCA Doppler and treated with intrauterine transfusion if hydrops develops.

Universal hepatitis C screening in pregnancy is now recommended.

HIV management has advanced to the point where vaginal delivery and breastfeeding are options with sustained undetectable viral loads.

References

• ACOG Practice Bulletin No. 151: Cytomegalovirus, Parvovirus B19, Varicella Zoster, and Toxoplasmosis in Pregnancy (2015, reaffirmed 2022)
• ACOG Practice Bulletin No. 236: Teratology (2021)
• CDC. Sexually Transmitted Infections Treatment Guidelines (2021)
• ACOG Committee Opinion No. 752: Prenatal and Perinatal HIV Testing (2018)
• ACOG Practice Advisory: Universal Hepatitis C Screening in Pregnancy (2021)
• SMFM Consult Series: Syphilis in Pregnancy (2022)
• Panel on Treatment of HIV During Pregnancy. Recommendations for Use of Antiretroviral Drugs in Pregnant Women. DHHS (2023)

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