Patient Presentation
A 9-day-old male came to clinic after discharge from the neonatal intensive care unit. Per the parents through an interpreter the baby was doing well. He was born to a G2P2 25 year old female who was from South America and had received some prenatal care there but not in the United States. She had presented to a local emergency room in labor, delivered and the mother and infant were transferred to a large medical center.

The pertinent physical exam in the NICU estimated him to be a 35-36 week gestation male, who was small for gestational age at 2.005 kg (5th), length 44 cm (5-10%), head circumference of 32 cm (25-50%). His examination was otherwise unremarkable.

The patient’s clinical course revealed that he had had some temperature instability that eventually resolved with warming. As his mother was treated for chorioamnionitis, he had laboratories tested which showed elevated inflammatory markers and he received antibiotics until 2 days later when the labs were normal and cultures were negative. At the outside hospital and in the NICU there were communication problems and the parents both emphasized the mother’s doctor told them it was important to let the baby’s doctors know about some issue to do with cats. Both were not able to provide more details except that they thought mother had been in the 2nd trimester of pregnancy when they were told this. Consequently in addition to the routine testing that occurs with this type of delivery, it was decided to also include TORCH titers, an eye examination and head ultrasound for a potential congenital infection especially toxoplasmosis; all of which were normal. He had slow feeding during his stay and eventually left the NICU at day 7. His examination in the office was unremarkable and he had the same weight as at discharge. He was to followup in 1 week with strict instructions for returning to the clinic or emergency room, and to continue his discharge feeding instructions with 24-kcal breast milk supplementation.

Discussion
Traditionally the mnemonic “TORCH” stood for the following intrauterine transmitted congenital infections:

T = Toxoplasmosis
O = Other = Syphilis
R = Rubella
C = Cytomegalovirus
H = Herpes simplex

Over time, this list has been expanded and sometimes is referred to as:

T = Toxoplasmosis
O = Other = Parvovirus, Varicella, Zika
R = Rubella
C = Cytomegalovirus, Chagas disease, COVID
H = Herpes simplex, Hepatitis B, HIV
E = Enterovirus
S = Syphilis

The list of clinically important congenital diseases, especially viruses, which have intrauterine transmission and should be considered in infants suspected of having a congenital infection, will likely continue to change over time. Many of these congenital infections can cause a variety of end-organ damage particularly to the central nervous system including the visual and auditory structures.

Note that some people will add clinically important bacterial infections such as Group B Streptococcus, Escherichia coli, and Listeria to this list as well. However many others will not as these bacterial infections are mainly perinatally transmitted, whereas TORCH infections are transmitted earlier in gestation.

Learning Point
Toxoplasmosis (Toxo) is caused by the parasite Toxoplasma gondii. Its definitive host are cats but there are other intermediates hosts (humans, rats and pigs). It is spread by ingestion of poorly cooked or raw meat with viable cysts, food or water contamination with cysts from cat feces, transplantation of infected tissues to naive host, and vertical transmission from mother to fetus. It is estimated that up to 1/3 of the world has had Toxo but clears the infection without problems. It is estimated that congenital toxoplasmosis (patient acquired through vertical transmission) incidence is from 0.1 – 6 per 1000 with higher rates in South America and the Middle East. There are four major strains worldwide.

In pregnant women, the infection may be asymptomatic or cause a mild “flu-like” illness. Pregnant women can transmit Toxo infection to their fetuses by acquiring a new infection, having had Toxo before but acquiring a new strain, or by potential reactivation of a prior infection (would be more common if immunocompromised). Depending on the timing of the maternal infection, the risks to the fetus change. In the first trimester, the placental vessels are smaller and therefore the transmission rate is lower (estimated at 5-15%) but transmission increases in the second and third trimester to 44% and 71% respectively. The risk of severe disease decreases with gestation however, with the more severely affected patients being those who acquired infection during the first trimester, and with ~85% infected in the third trimester being asymptomatic.

Laboratory testing for Toxo includes antibody tests, and other tests from blood, amniotic fluid and cerebrospinal fluid. Test interpretation depends on the specific test and timing of suspected infection. IgM usually appears within first 1-2 weeks of infection. IgG appears at least 2 weeks after infection and generally is life-long. Significantly increased IgM or IgG in a newborn compared to the mother is suggestive of congenital infection in the newborn.

Clinically the infant may have no obvious signs of congenital toxoplasmosis at birth but some can have symptoms that appear later. The classic triad of congenital toxoplasmosis is chorioretinitis (bilateral), intracranial calcifications and hydrocephalus. Other manifestations include:

• Central Nervous System
  • Intracranial calcifications
  • Hydrocephalus
  • Encephalopathy
  • Microcephaly
  • Hearing impairment
  • Motor impairments
  • Seizures
• Eyes
  • Chorioretinitis
  • Microphthalmia
  • Cataract
  • Optic nerve atrophy
  • Nystagmus
  • Strabismus
  • Retinal scarring
• Liver
  • Hepatosplenomegaly
  • Hepatic calcification
  • Jaundice
• Cardiorespiratory
  • Myocarditis
  • Pneumonitis
• Systemic
  • Small for gestational age
  • Fever
  • Rash (can be “blueberry muffin”)
  • Bone marrow suppression
• Prenatally
  • Intrauterine growth restriction
  • Fetal demise
  • Ascites
  • Hydrops fetalis
  • Polyhydramnios
  • Pericardial effusions

Treatment is specialized for mothers and infants which may be needed for long periods of time. Prevention includes maternal education for not handling cat feces, ingesting undercooked meat, or food or water which potentially could be contaminated.

Questions for Further Discussion
1. What other diseases occur in your area which are added to your own TORCH differential diagnosis?
2. What are routine lab tests to obtain for a pregnant mother for screening for infections?
3. What are the basic first steps for newborn resuscitation?

Related Cases

Disease: Toxoplasmosis

Symptom/Presentation: Health Maintenance and Disease Prevention

Specialty: Infectious Diseases | Neonatology | Obstetrics / Gynecology

Age: Premature Newborn

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at MedlinePlus for this topic: Toxoplasmosis

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Saso A, Bamford A, Grewal K, et al. Fifteen-minute consultation: Management of the infant born to a mother with toxoplasmosis in pregnancy. Arch Dis Child Educ Pract Ed. 2020;105(5):262-269. doi:10.1136/archdischild-2018-316603

Moodley A, Payton KSE. The Term Newborn. Clinics in Perinatology. 2021;48(3):485-511. doi:10.1016/j.clp.2021.05.004

Caceres A, Caceres-Alan A, Caceres-Alan T. Toxoplasma gondii infections in pediatric neurosurgery. Childs Nerv Syst. 2024;40(2):295-301. doi:10.1007/s00381-023-05915-2

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa