Approach to congenital infections: Clinical sciences

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Introduction 0:00–0:55

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.

H&P 0:55–2:15

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.

Rubella 2:15–4:10

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!

Heart murmur absent 4:10–4:23

Your next step is to assess head circumference. If you identify microcephaly, your next step is to look for skin rash.

Microcephaly/rash4:23–4:35

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.

Cytomegalovirus 4:35–6:07

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.

Toxoplasmosis 6:07–7:17

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.

Zika 7:17–8:16

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.
Now that we’ve considered patients with microcephaly, let’s discuss patients with a normal head circumference. For these patients, the first step is to look for abnormal skin findings.

Normal head circumference 8:16–8:29

If you notice abnormal skin findings, assess the skin’s appearance. If your patient has vesicular rash or cutaneous scarring, assess the maternal history for a rash.

Abnormal skin findings 8:29–8:42

If there is widespread vesicular rash, consider varicella-zoster virus infection. If the maternal history includes a widespread vesicular rash that appeared from 5 days before the delivery to 2 days after delivery, consider varicella-zoster virus infection.

Varicella-zoster virus 8:42–10:49

In this case, the newborn will have been infected with the varicella-zoster virus transplacentally. But because this time frame is too short for the fetus to receive transplacental antibodies, the newborn will be at high risk of developing neonatal varicella, which is a fulminant infection associated with high morbidity and mortality.
These infants may have a history of irritability or fever; and the exam typically demonstrates vesicular skin lesions. In this case, obtain a varicella PCR from vesicular fluid.
You could also obtain an IgM titer, which is an indicator that a recent infection has occurred. A positive PCR, with a possible positive IgM titer, confirms your diagnosis of neonatal varicella-zoster infection.
Here’s a high yield fact! The timing of the varicella infection impacts the severity of its sequelae.
If the maternal rash begins more than a week before delivery, the newborn may develop a vesicular rash but is not at high risk of severe disease, since enough maternal antibodies will have transferred across the placenta.
These infants may also develop zoster during the first 2 years of life. However, if fetal infection occurs during the first 20 weeks of gestation, congenital varicella syndrome can result.
This can cause spontaneous abortion, intrauterine fetal demise, and defects that include cerebral cortical atrophy, cerebellar aplasia, microcephaly, and severe developmental anomalies, as well as cutaneous scars, aplasia cutis, or limb hypoplasia; and ocular defects like microphthalmia and cataracts.
Now let’s switch gears and consider infants whose mothers had active genital lesions at the time of delivery. In this case, consider herpes simplex virus, or HSV infection.

HSV 10:49–12:34

Congenital HSV is usually acquired during labor and delivery when there’s shedding of the virus from the genital tract. Although it’s much less common than other congenital infections, congenital HSV is associated with severe morbidity and mortality.
The newborn might display irritability and lethargy; and occasionally, seizures or tremors. The physical examination may demonstrate fever or temperature instability.
You may also detect a bulging fontanelle, keratoconjunctivitis, or vesicular lesions of the skin, eyes, and mouth. To evaluate, order an HSV PCR of the blood and CSF; and viral culture of the skin, eyes, mouth, rectum, or blood.
Also, remember to obtain an MRI of the brain. If the labs reveal a positive PCR or culture, and if MRI demonstrates edema and parenchymal changes consistent with encephalitis, diagnose HSV infection.
Here’s another high-yield fact! Neonatal HSV can present as a localized infection of the skin, eyes, and mouth; disseminated disease affecting multiple organ systems such as the liver and lungs; and encephalitis.
These 3 presentations can overlap and cause significant morbidity and mortality if not treated promptly. Now let’s go back and consider patients with a maculopapular rash.

Syphilis 12:34–13:54

The maternal history might reveal limited prenatal care or a genital chancre. The newborn exam is typically normal at birth, but by 1 to 2 months of age infants may develop a desquamative maculopapular rash, often seen on the palms, soles, or diaper area; and snuffles, which is rhinitis with mucopurulent nasal discharge.
Other common findings include pseudoparalysis, caused by bone inflammation resulting in severe pain during movement; epitrochlear lymphadenopathy; and condyloma lata, which are wart-like lesions on moist areas of skin.
With these findings, consider syphilis and obtain a VDRL or RPR of the blood or CSF. If either test is positive, diagnose congenital syphilis, which is caused by the spirochete Treponema pallidum.
Now here’s a clinical pearl! Late congenital syphilis presents after two years of age with oral findings, such as Hutchinson teeth and mulberry molars.
Affected children can also develop deafness, interstitial keratitis, and skeletal abnormalities, such as saber shins. Finally, let’s discuss newborns with a normal head circumference and no abnormal skin findings.

HIV 13:54–15:01

In this case, consider congenital human immunodeficiency virus, or HIV infection, which is most often transmitted during labor and delivery.
The maternal history may reveal limited or no prenatal care or a known history of HIV. Infected newborns are commonly asymptomatic, but later in infancy, they may develop opportunistic infections, poor weight gain, and developmental delay.
Exam findings in the newborn period are usually normal. If you suspect HIV, order an HIV RNA or DNA NAAT.
If either test is positive, diagnose HIV infection. Here’s one final clinical pearl!
In addition to the traditional TORCH infections, keep in mind that many Other pathogens can cause congenital infections such as enterovirus, hepatitis B, parvovirus B19, and Listeria monocytogenes.
Alright, as a quick recap… If you suspect a congenital infection, clues from the history and physical can guide your diagnostic evaluation.

Review 15:01–16:10

The presence of a heart murmur, cataracts, and hearing loss is suggestive of congenital rubella. Consider CMV infection for microcephaly, rash, and hearing loss, without cat exposure.
On the other hand, microcephaly, rash, and chorioretinitis, along with cat exposure is specific to toxoplasmosis. The presence of severe microcephaly without rash suggests Zika infection.
On the flip side, a normal head circumference and a vesicular rash during pregnancy suggest varicella-zoster; but if active genital lesions are present at delivery, diagnose HSV infection.
Next, a rash and snuffles at 1 to 2 months of age suggest congenital syphilis. Finally, infants with a normal newborn exam who develop opportunistic infections and poor weight gain later in infancy might have congenital