• Toxoplasmosis (Toxo): 1 per 10,000 to 1 per 1,000 live births in the US.
  
• Syphilis: 13.4 per 100,000 live births in the US.
  
• CRS: Pre-vaccine era 20,000 cases per year (1963-1965); in 2008, 11 cases were reported in US.
  
• CMV: 30,000 to 40,000 cases per year; 1% of live newborns in the US, whereas 0.3% to 2.4% in other developed countries.
  
• HSV: 1,500 infants per year.

• Toxo: 10% to 20% symptomatic at birth.
  
• Syphilis:

• Early congenital: Birth to 2 years of age.
  
• Late congenital: After age 2 years.

• CRS: Birth.
  
• CMV: 5% to 18% symptomatic at birth, 10% to 15% manifest symptoms later in infancy; most won’t develop any symptoms at all.
  
• HSV: Birth to 6 weeks.

• Toxo: Toxoplasma gondii (T. gondii), maternal contact with cat feces, ingestion of undercooked pork, eggs, and unpasteurized milk.
  
• Syphilis: Treponema pallidum, maternal infection.
  
• CRS: Rubella virus, maternal infection, or re-infection—viremia and vertical transmission during the first 16 weeks of pregnancy.

• Seasonality: Spring.

• CMV: Maternal infection, person-to-person via body fluids, viremia and vertical transmission.
  
• HSV: HSV types I and II ~75%, enters epidermis and/or mucosal surfaces, hematogenous and transplacental transmission; perinatal through infected birth canal.

Toxo: Classic triad of obstructive hydrocephalus, chorioretinitis and intracerebral calcifications.

• General: Fever, malaise, sepsis.
  
• Skin: “Blueberry muffin” rash (extramedullary hematopoiesis).
  
• Hematologic: Eosinophilia, anemia, extramedullary hematopoiesis.
  
• Gastrointestinal: Vomiting, diarrhea, hepatosplenomegaly, direct hyperbilirubinemia.
  
• Central nervous system (CNS): Microcephaly, hydrocephaly, intracranial calcifications, seizure disorder, learning disability.
  
• Ophthalmologic: Chorioretinitis, microphthalmia, cataracts, visual impairment.
  
• Pulmonary: Pneumonitis.

Congenital syphilis:

• Early congenital: Stillbirth, inflammation, or hardening of the umbilical cord, papulosquamous rash, fever, low birth weight, aseptic meningitis, hepatosplenomegaly, jaundice, periostitis, rhinitis, often bloody (snuffles).
  
• Late congenital: Hutchinson teeth (notched incisors), interstitial keratitis, deafness (Hutchinson triad, 63% of cases); frontal bossing, saddle nose deformity, saber shins.

CRS: Classic triad of congenital cataracts, deafness, and cardiac defects.

• Toxo: IgM 1 to 2 weeks of life; IgA present in >95% of acute infections; IgG and IgE present in nearly all mothers who seroconverted during pregnancy; CSF + IgM in the neonate; long-bone films show metaphyseal lucency and irregular epiphyseal calcifications; polymerase chain reaction (PCR) testing of body fluids and staining of biopsy specimens with T. gondii-specific immunoperoxidase to confirm diagnosis.
  
• Syphilis: Routine maternal screening; non-treponemal testing: Venereal Disease Research Laboratory (VDRL) and rapid plasma regain (RPR); treponeme-specific testing: fluorescent treponemal antibody-absorbed (FTA-ABS) testing, the microhemagglutination testing for T. pallidum (MHA-TP), T. pallidum environmental impact assessment (TP-EIA); TP-EIA has become a favored test because of its lower cost, and, in many cases, higher sensitivity; “reverse” screening used more, syphilis IgG first, then, in order RPR and TP-PA performed as needed to confirm infection; CSF evaluation required for diagnosis of neurosyphilis.
  
• CRS: Routine maternal immunity screen; isolation of rubella virus from respiratory secretions, urine, CSF, and/or tissue biopsy.
  
• CMV: Virus detection in urine, saliva, or blood; PCR ± positive IgM; prenatal diagnosis; CMV isolation from amniotic fluid, anti-CMV IgM in percutaneous umbilical cord blood.
  
• HSV: Lesional HSV direct fluorescent antibody (DFA) and viral culture.

NICU admission, infectious disease, ophthalmology, neurology, audiology evaluations; developmental specialists, cardiology, gastroenterology, neurosurgery; multidisciplinary support.

• Toxo: Fetal infection—sulfadiazine, pyrimethamine, folinic acid; patients who do not tolerate sulfonamides can be treated with pyrimethamine, clindamycin, atovaquone, or azithromycin; infantile infection combination therapy, experimental, ± corticosteroids.
  
• Syphilis: Drug of choice, aqueous penicillin G, 100,000 to 150,000 U/kg/d intravenous (IV) every 8 to 12 hours for 10 to 14 days for newborns; if >4 weeks, then 200,000 to 300,000 U/kg/d IV divided every 6 hours for 10 to 14 days achieves adequate CSF concentration; alternate is procaine penicillin G, 50,000 U/kg intramuscular, though may not achieve adequate CSF concentration.
  
• CRS: Supportive therapy.
  
• CMV: Ganciclovir (experimental); associated with bone marrow toxicity.
  
• HSV: IV acyclovir until HSV is confirmed or ruled out.