para>Antibiotic treatment may provoke early labor or fetal distress (Jarisch-Herxheimer reaction) but should not be delayed (1)[A].
Rubella: Test IgG titers to determine immunity at initial prenatal visit. Vaccinate non-immune patients prior to pregnancy or during thepostpartum period.
CMV: Avoid prolonged exposure to young children during pregnancy; hand washing; insufficient evidence for immunoglobulin or vaccine use (2)[A]
Herpes: Cesarean delivery for active genital lesions decreases transmission; insufficient evidence that antiviral prophylaxis decreases neonatal herpes incidence, although it does decrease viral shedding, clinical lesions, and number of cesarean sections. Prophylactic treatment with acyclovir 200 mg QID or 400 mg TID or valacyclovir 500 mg BID starting at 36 weeks ' gestation. Recommend treatment with acyclovir of the asymptomatic neonate delivered to mother with active lesions until neonatal PCR and viral cultures are negative and maternal serology and polymerase chain reaction (PCR) indicate a recurrent episode (3)[A],(4)[C].
DIAGNOSIS
HISTORY
- Toxoplasmosis: Acute infection of mother is usually asymptomatic.
- Syphilis, Rubella, and CMV: maternal history of fever and rash
- Herpes: 60 " 80% of newborn infections occur in mother with no known prior genital lesions.
PHYSICAL EXAM
- Common features: microcephaly, intracranial calcifications, rash, intrauterine growth restriction, jaundice, hepatosplenomegaly, hepatitis, and thrombocytopenia
- Toxoplasmosis: hydrocephalus, diffuse intracranial calcifications or ventricular dilatation, and chorioretinitis
- Syphilis: Majority of infants asymptomatic; early signs are snuffles (rhinitis), poor feeding, retinitis, jaundice, and hepatosplenomegaly; rash varies from red macular to bullous; chronic infection may present with neurosyphilis (tabes dorsalis, deafness), Hutchinson incisors, mulberry molars, saddle nose deformity, or uveitis.
- Rubella: Classic triad involves sensorineural hearing loss, ocular abnormalities (cataracts, glaucoma, retinopathy), and congenital heart disease (patent ductus arteriosus [PDA]).
- CMV: Most infected infants are asymptomatic; 10% with symptoms including common features mentioned earlier; petechiae and purpura (blueberry muffin rash), deafness, chorioretinitis
- Herpes: vesicular lesions on skin, eyes, or mouth; fever; irritability; focal neurologic symptoms
DIFFERENTIAL DIAGNOSIS
- Congenital lymphocytic choriomeningitis virus
- Encephalopathies
- Meningitis
- Parvovirus B19 (fifth disease/erythema infectiosum)
- Bacterial sepsis
- HIV
- Varicella
- Epstein-Barr virus
- Enteroviruses
- Hepatitis B
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Toxoplasmosis: Isolation of organism from serum/ CSF is definitive but difficult; newborn serum testing of IgM and IgA antibodies; maternal blood enzyme linked immunoassay (EIA); head CT (ring-enhancing lesions, diffuse calcifications (5)
- Syphilis: Newborn screen with VDRL or RPR test, confirm with FTA-ABS; CSF for VDRL, cell count, and protein; chest x-ray (CXR) (pneumonia alba); long bone x-ray (onion-skinning, rat bite tibia) (6)
- Rubella: Viral isolation by PCR preferred over serologic testing.
- CMV: DNA PCR or viral culture from urine or saliva in first 3 weeks of life; PCR on dried blood spot available for retrospective testing but low sensitivity (34 " 100%); cranial ultrasound (Periventricular intracranial calcifications, white matter loss, ventriculomegaly, microgyria) (2,7)[A]
- Herpes: HSV culture of vesicle, mucosal surfaces; CSF PCR; MRI brain if concern for encephalitis
Follow-Up Tests & Special Considerations
- Rubella: Echocardiography to diagnose heart defects; CT of the brain may show intracranial calcifications. Audiometric testing for hearing loss
- CMV: Brain MRI for symptomatic newborns or if abnormalities visualized on cranial ultrasound
- HSV: If CSF PCR positive, repeat LP until PCR DNA negative prior to discontinuing antivirals (4)[C].
Diagnostic Procedures/Other
- Toxoplasmosis: opthalmic exam
- Rubella and CMV: ophthalmic and audiology evaluation
- Herpes: ophthalmic exam
TREATMENT
GENERAL MEASURES
- Nutritional and respiratory support
- Phototherapy for hyperbilirubinemia
MEDICATION
First Line
- Toxoplasmosis: Pyrimethamine (1 mg/kg/day PO daily for 6 months, then Monday, Wednesday, Friday for 6 months; max 25 mg/day) and sulfadiazine (100 mg/kg/day PO q12h) for 12 months in both symptomatic and asymptomatic infants. Folinic acid (5 to 10 mg 3 times/week) to reduce hematologic toxicity (7)[B]
- Syphilis: Aqueous crystalline penicillin G 50,000 U/kg IV q12h for 7 days, then q8h for total treatment of 10 days. Desensitize patient if penicillin-allergic (1)[A].
- Rubella: No specific antiviral agent indicated.
- CMV: Ganciclovir 6 mg/kg IV q12h for 6 weeks for severe disease or CNS symptoms (8)[A]
- Herpes: Insufficient evidence to evaluate antiviral use in neonates; recommended treatment is acyclovir 20 mg/kg IV q8h for 14 to 21 days (4)[C],(9)[A].
Second Line
- Syphilis: Procaine penicillin G 50,000 U/kg IM daily for 10 days (1)[A].
- CMV: valganciclovir 15 mg/kg PO BID for 6 weeks (off-label use) (8)[A]
ISSUES FOR REFERRAL
Consider consultation based on organ systems involved (ophthalmology, cardiology, neurology, and orthopedics).
SURGERY/OTHER PROCEDURES
- Possibility of gastrostomy placement based on nutritional needs
- Rubella: Repair of congenital heart defects
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Infected neonates to remain inpatient from birth; respiratory support
IV Fluids
Indicated if oral feeding is inadequate; determined by weight-based calculations
Discharge Criteria
Once stable and treatment is completed or arranged on outpatient basis; infants infected with rubella must remain hospitalized in isolation until 2 cultures taken 1 month apart are negative.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
- Continue to follow neurologic and developmental status.
- Toxoplasmosis: Follow-up every 2 weeks until stable, then monthly while being treated; weekly CBC for 1 month, then every 2 weeks
- Syphilis: Serologic testing every 2 to 3 months until nonreactive or 4-fold titer decrease (should occur by 6 months of age, otherwise, repeat LP and treatment). If CSF is abnormal, repeat LP every 6 months until normal (1)[A].
- Rubella: vision and hearing screening
- CMV: Hearing screens every 2 to 3 months until age 3 years, then annually until age 6 years; annual eye exam until age 5 years for symptomatic newborns; CBC and LFTs weekly during treatment (risk of pancytopenia/hepatitis toxicity) (2)[A]
DIET
Normal diet without restrictions, as tolerated
PATIENT EDUCATION
- An infected mother should be informed of potential harm to the fetus.
- Pregnant women should avoid contact with those infected with rubella.
PROGNOSIS
- Toxoplasmosis: Development and behavior normal with adequate treatment; chorioretinitis in 26% of treated infants
- Syphilis: 6.4% mortality rate; poor if symptomatic in first few weeks of life
- Rubella: Generally patients ' possess a poor outcome with significant organ damage.
- CMV: Normal development if 12-month exam within normal limits; chorioretinitis untreatable.
- Herpes: 30% mortality of treated disseminated disease; good outcome with treated mucocutaneous infections
COMPLICATIONS
- Toxoplasmosis: meningoencephalitis with hydrocephalus, seizure disorder, vision impairment, deafness, and mental retardation
- Syphilis: pneumonia alba, stillbirth, and multiple organ damage
- Rubella: deafness, vision impairment, skeletal defects, and congenital heart defects
- CMV: progressive, delayed hearing loss, chorioretinitis, and pancytopenia
- Herpes: seizures, pneumonia, adrenal involvement, respiratory distress, liver dysfunction, and eczema herpeticum
REFERENCES
11 Workowski KA, Berman S, Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010;59(RR " 12):1 " 110.22 Goderis J, De Leenheer E, Smets K, et al. Hearing loss and congenital CMV infection: a systematic review. Pediatrics. 2014;134(5):972 " 982.33 Hollier LM, Wendel GD. Third trimester antiviral prophylaxis for preventing maternal genital herpes simplex virus (HSV) recurrences and neonatal infection. Cochrane Database Syst Rev. 2008;(1):CD004946. doi:10.1002/14651858.cd004946.pub2.44 Kimberlin DW, Baley J, Committee on Infectious Diseases and Committee on Fetus and Newborn. Guidance on management of asymptomatic neonates born to women with active genital lesions. Pediatrics. 2013;131(2):e635 " e646.55 Del Pizzo J. Focus on diagnosis: congenital Infections (TORCH). Pediatr Rev. 2011;32(12):537 " 542.66 Cohen SE, Klausner JD, Engelman J, et al. Syphilis in the modern era: an update for physicians. Infect Dis Clin North Am. 2013;27(4):705 " 722.77 Mcleod R, Boyer K, Karrison T, et al. Outcome of treatment for congenital toxoplasmosis, 1981 " 2004: the National Collaborative Chicago-Based, Congenital Toxoplasmosis Study. Clin Infect Dis. 2006;42(10):1383 " 1394.88 Kadambari S, Williams EJ, Luck S, et al. Evidence based management guidelines for the detection and treatment of congenital CMV. Early Hum Dev. 2011;87(11):723 " 728.99 Jones CA, Walker KS, Badawi N. Antiviral agents for treatment of herpes simplex virus infection in neonates. Cochrane Database Syst Rev. 2009;(3):CD004206.
ADDITIONAL READING
- Anzivino E, Fioriti D, Mischitelli M, et al. Herpes simplex virus infection in pregnancy and in neonate: status of art of epidemiology, diagnosis, therapy and prevention. Virol J. 2009;6:40.
- Control and prevention of rubella: evaluation and management of suspected outbreaks, rubella in pregnant women, and surveillance for congenital rubella syndrome. MMWR Recomm Rep. 2001;50(RR-12):1 " 23.
- de Jong EP, Vossen AC, Walther FJ, et al. How to use... neonatal TORCH testing. Arch Dis Child Educ Pract Ed. 2013;98(3):93 " 98.
CODES
ICD10
- P00.2 Newborn affected by maternal infec/parastc diseases
- P37.1 Congenital toxoplasmosis
- P35.1 Congenital cytomegalovirus infection
- P35.2 Congenital herpesviral [herpes simplex] infection
- P39.8 Other specified infections specific to the perinatal period
- P35.0 Congenital rubella syndrome
ICD9
- 760.2 Maternal infections affecting fetus or newborn
- 771.2 Other congenital infections specific to the perinatal period
- 771.1 Congenital cytomegalovirus infection
- 771.89 Other infections specific to the perinatal period
- 771.0 Congenital rubella
SNOMED
toxoplasmosis, other infections, rubella, cytomegalovirus, and herpes simplex virus (TORCH) syndrome (disorder)
CLINICAL PEARLS
- Ensuring patients receive adequate prenatal care is paramount for prevention of TORCH infections.
- TORCH infections may present similarly; targeted diagnostic workups are indicated based on clinical presentation.
- Providers should remain diligent to possible neonatal HSV given that the majority of cases occur in mothers with no prior history of genital lesions.
- Sequelae of TORCH infections may have delayed presentations and those impacted require close follow up.