Approach to congenital infections: Clinical sciences

Congenital infections occur when a bacterial, viral, or parasitic pathogen crosses the placenta during pregnancy or is acquired by the newborn during labor and delivery.

While some congenital infections are asymptomatic, many are associated with significant sequelae such as intrauterine growth restriction, microcephaly, hearing loss, and ocular abnormalities.

Traditionally, congenital infections have been grouped under the mnemonic TORCH, which stands for Toxoplasma, Other, Rubella, Cytomegalovirus, and Herpes simplex virus. The category Other continues to evolve and includes pathogens such as Zika virus, Varicella-zoster virus, syphilis, and human immunodeficiency virus.

When a patient presents with a chief concern suggesting a congenital infection, your first step is to obtain a focused history and physical examination.

This includes measurement of weight, length, and head circumference; as well as a fundoscopic exam and a hearing screen.

The antenatal history may reveal signs or symptoms of a maternal infection during the pregnancy; immunosuppression, or there might be no prenatal care.

The neonatal history may reveal that the infant was small for gestational age at birth; and the physical exam findings could include jaundice, hepatosplenomegaly or hsm, rash, or congenital malformations, depending on the type of infection. With these findings, consider the possibility of a congenital infection.

Now here’s a clinical pearl to keep in mind! Various congenital infections present with jaundice, hepatosplenomegaly, and rash, so consider ordering a CBC and CMP during your initial workup. The CBC commonly demonstrates anemia and thrombocytopenia, while the CMP may demonstrate elevated serum bilirubin levels. Remember, these findings aren’t specific, so correlate the results with clinical findings to focus your diagnostic evaluation!

Once you’ve considered a congenital infection, begin your evaluation by assessing for a heart murmur.

If you detect a murmur, consider congenital rubella. In this case, a review of the maternal history often reveals a mild febrile illness or rash early in pregnancy.

The newborn exam will demonstrate a bluish-purple maculopapular rash, called a blueberry muffin rash, which is due to dermal hematopoiesis. A systolic or continuous machinery-like heart murmur that radiates from the left upper sternal border to the back will also be present. The eye examination may reveal cataracts, glaucoma, or salt-and-pepper retinopathy, while a hearing screen commonly demonstrates sensorineural hearing loss or SNHL.

Next, obtain a rubella IgM titer and viral cultures of the blood, urine, cerebrospinal fluid, and oral or nasal secretions. Additionally, consider obtaining IgG titers, and don’t forget to order an echocardiogram.

If the IgM titer or the cultures are positive or if IgG titers are rising, and the echocardiogram reveals patent ductus arteriosus or peripheral pulmonary stenosis, diagnose congenital rubella.

Here’s a clinical pearl to keep in mind! Congenital rubella is rare in developed countries due to widespread vaccination, but if an unvaccinated patient becomes infected during pregnancy, gestational age impacts disease severity. Infection before 4 weeks of gestation can cause pregnancy loss, while infection between 4 weeks and 4 months often causes congenital defects. However, infection after 4 months usually doesn’t cause sequelae.

Now let’s go back and take a look at newborns and infants with no heart murmur! Your next step is to assess head circumference.

If you identify microcephaly, your next step is to look for skin rash. If a skin rash is present, assess for maternal exposure to cats or cat feces. When there’s a combination of microcephaly and a rash, but no exposure to cats, consider cytomegalovirus, or CMV infection.

There might be a maternal report of a mild flu-like illness during pregnancy; and the neonatal history often reveals that the infant was premature or small for gestational age. The newborn is usually asymptomatic at birth, though they may develop seizures and developmental delay later.

The newborn exam typically demonstrates a blueberry muffin rash; while fundoscopy findings include chorioretinitis and retinal hemorrhage; and the hearing screen reveals sensorineural hearing loss.

To confirm the diagnosis, order a urine or salivary polymerase chain reaction, or PCR, and consider a viral culture of the blood or cerebrospinal fluid. Finally, obtain an MRI of the brain.
Positive PCR testing or cultures, with imaging findings of periventricular cysts or calcifications, and ventriculomegaly, confirm the diagnosis of congenital CMV infection.

Here’s a high-yield fact! Since most reproductive-aged patients are seropositive for CMV, prenatal screening isn’t routinely performed. During pregnancy, primary infection poses the highest risk to the fetus, but reactivation of latent maternal infection can also cause congenital CMV.

Alright, now let’s discuss patients with microcephaly, a rash, and an exposure to cats or cat feces.

In this case, consider a Toxoplasma gondii infection. In addition to exposure to cats, the maternal history may include an exposure to raw meat or milk, or contaminated soil or water. The newborn is likely to be asymptomatic at birth but may develop seizures.

The physical exam commonly reveals a blueberry muffin rash, hypotonia, and microphthalmia; and the eye exam typically demonstrates chorioretinitis.

To confirm the diagnosis, order a Toxoplasma IgA, IgG, and IgM titer; a PCR of the placenta, blood, or CSF; and an MRI of the brain.

If the titers and PCR are positive and the imaging demonstrates cortical intracranial calcifications, hydrocephalus, and ventriculomegaly, diagnose congenital toxoplasmosis, caused by the parasite Toxoplasma gondii.

Next, let’s discuss patients who have microcephaly but no skin rash. In this case, consider a Zika virus infection. The maternal history may include travel or residence in an endemic region, or a mild viral illness during pregnancy.

The newborn exam may demonstrate severe microcephaly, hypertonia, and possibly contractures such as clubfoot; while the fundoscopic exam might reveal macular scarring and chorioretinal atrophy.

To confirm the diagnosis, obtain nucleic acid amplification, or NAAT testing for Zika virus as well as IgM titers and an MRI of the brain or head ultrasound. If the NAAT and IgM titers are positive, and imaging demonstrates cerebellar hypoplasia, ventriculomegaly, or lissencephaly, diagnose congenital Zika infection.