A 2 week old neonate presents to the outpatient office for a weight check after recently moving from out-of-state. No newborn records have been sent from the previous hospital, and the mother is unsure of her prenatal testing, although she states delivery was uneventful. She is concerned because of a rash that has developed over the past day, and he seems smaller compared to his older brother when he was the same age. On exam, you note a murmur, a petechial rash over his entire body, and his weight is below the first percentile. What is the most likely cause of this infant’s symptoms?
A. Congenital Parvovirus B19
B. Congenital Cytomegalovirus
C. Congenital Rubella
D. Congenital Syphilis
E. Congenital Toxoplasmosis
The correct answer is C, Congenital Rubella. We will need to dive into the specifics of each disease given that they all lead to overlapping features of IUGR (or SGA post-natally) and multi-organ system involvement.
Answer Choice A: Congenital Parvovirus B-19
This is not the correct answer due to the clinical presentation. The typical presentation of parvovirus B-19 in the neonatal period is extremely severe with isolated pleural and pericardial effusions, fetal hydrops, and a high risk of fetal death. The greatest risk of mortality is present if transmission occurs in the first half of pregnancy with the overall risk being between 2-6%. The diagnosis is made with a positive serum IgM specific for Parvovirus, indicating that the infection occurred 2-4 months prior. Being a virally-mediated disease process, the treatment is typically limited to supportive care.
Answer Choice B: Congenital Cytomegalovirus
The presentation of this patient is not consistent with Congenital Cytomegalovirus, commonly known as CMV. The vast majority of infants with congenital CMV are asymptomatic at birth but if symptoms are present they will most likely include IUGR, jaundice, hepatosplenomegaly, microcephaly, thrombocytopenia, intracranial calcifications, and hearing loss. The easiest way to remember congenital CMV is with the 4 C’s of CMV:
– Central cerebral calcifications (Periventricular)
– Potential for “C”ensorineural hearing loss (Sensorineural)
These babies can also have thrombocytopenia with subsequent petechiae and purpura (blueberry muffin rash) but will typically NOT have cardiac involvement and will NOT have an audible heart murmur. The diagnosis is made by CMV-specific PCR, which can be run on urine, stool, saliva, CSF, or blood, and IgM can be tested within 3 weeks of birth. The treatment is Ganciclovir 6mg/kg/dose IV BID for 6 weeks OR Valganciclovir 16mg/kg/dose PO BID.
Answer Choice C: Congenital Rubella
The history and exam findings in this patient are consistent with Congenital Rubella. Infants present with IUGR (then SGA) cataracts, cardiac anomalies, deafness, and the classic blueberry muffin rash. If suspecting this diagnosis, it is important to obtain an IgM level, which will be positive between 0-3 months of age. Early eye exam and echocardiogram are important for initial diagnosis and to continue to closely monitor and intervene as necessary. Patent Ductus Arteriosus and Pulmonary Valve Stenosis are the two most common cardiac anomalies associated with congenital rubella. White matter anomalies and periventricular calcifications are often present, as are calcifications in the basal ganglia. Given this is a virally mediated process, the treatment remains largely supportive, and it is incredibly important to vaccinate mom! It is important to note that the risk of congenital infection and defects resulting from such is highest during the first 12 weeks of gestation and decreases thereafter; defects are rare after infection in the 20th week (or later) of gestation. This presents a substantial problem due to the fact that a significant portion of mothers may present for prenatal care after this time period. In similar fashion to CMV, these infants need to be followed well into childhood due to the high rate of hearing dysfunctions associated with this congenital infection.
Answer Choice D: Congenital Syphilis
The presentation of this patient is not consistent with Congenital Syphilis, which is likely to present with more mucocutaneous lesions, hepatosplenomegaly, snuffles, lymphadenopathy, osteochondritis, hemolytic anemia, or thrombocytopenia. Of note, the skin and all secretions are highly contagious! If the mother has adequate prenatal care, this is something that is routinely tested for. However, depending on timing of testing and contraction of illness, it does have potential to be missed. Of note, if maternal serology is positive, the infant should be screened with a VDRL test or RPR (more common) and confirmed with Fluorescent treponemal antibody absorption test (FTA-ABS) or microhemagglutination assay for treponema pallidum antibodies (MHA-TP). If the infant is positive on confirmatory testing, treatment should be initiated with penicillin G.
Answer Choice E: Congenital Toxoplasmosis
Lastly, this patient does not fit the picture of Congenital Toxoplasmosis given the clinical history and physical exam. The vast majority of infants affected by Congenital Toxoplasmosis are asymptomatic at birth. If there are symptoms present, they typically include a maculopapular rash (as opposed to the purpuric one seen with Congenital Rubella), generalized lymphadenopathy, hepatosplenomegaly, jaundice, pneumonitis, petechiae, and thrombocytopenia. Similar to other congenital infections, microcephaly, chorioretinitis, seizures, and hearing loss are common manifestations of infection. It is even more common for this disease process to not present until later in life with seizures, developmental delay, learning disabilities, and cognitive deficits. It is interesting to note that when Toxoplasmosis occurs early in pregnancy, there is a lower chance of fetal infection, but when infection does occur, the consequences are more severe with the opposite holding true later in pregnancy with a greater chance of infection but less severe sequela. Diagnosis is made by the presence of IgM or IgA immediately or by IgG if testing after 1 year of age. Treatment is with pyrimethamine, sulfadiazine, and folinic acid for at least 1 year.
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- Coller RJ. (2018). Board Review Series: Pediatrics. 2nd ed. Lippincott Williams & Wilkins.
American Academy of Pediatrics. Kimberlin DW, Brady, MT, Jackson MA, Long SS. Red Book: 2018 Report of the Committee on Infectious Diseases, 31st ed. American Academy of Pediatrics, Itasca, IL 2018.
- Rowe RD. Maternal rubella and pulmonary artery stenoses: report of eleven cases. Pediatrics. 1963 Aug;32:180-5. PMID: 14044445.