Intrauterine infection (IUI) is defined as an infection occurring within the uterus that affects the fetus, the surrounding amniotic fluid, or the fetal membranes and placenta before or during birth. This complication is a significant contributor to global neonatal morbidity and mortality. IUI is recognized as a major cause of complications such as preterm premature rupture of membranes and preterm birth.
Pathways of Fetal Exposure
Pathogens can gain access to the fetus through two primary mechanisms, each dictating the type of infection likely to occur. The first and most common route for bacterial infection is the ascending pathway, where microorganisms move upward from the mother’s lower genital tract. Bacteria residing in the vagina or cervix travel into the amniotic fluid and membranes, often resulting in an infection known as chorioamnionitis. This pathway is particularly likely if the amniotic sac has ruptured.
The second major mechanism is the hematogenous, or transplacental, route, which is the standard way viruses and parasites reach the developing fetus. The pathogen enters the mother’s bloodstream, crosses the placenta, and is transmitted directly into the fetal circulation. The placenta can also be a site of infection itself, facilitating the passage of microorganisms. Less commonly, infection can occur iatrogenically, meaning it is introduced during a medical procedure such as an amniocentesis.
Major Infectious Agents
A significant group of pathogens capable of crossing the placenta is known by the acronym TORCH, representing Toxoplasmosis, Other agents, Rubella, Cytomegalovirus, and Herpes Simplex. These agents persist and cause systemic damage because the fetal immune system is unable to fully clear the infection. The ‘O’ in TORCH encompasses several other severe infections, including syphilis, varicella-zoster virus, and parvovirus B19.
Cytomegalovirus (CMV), the most common congenital infection, is noteworthy for its ability to cause serious long-term damage even when the mother has no symptoms. Rubella virus acts as a potent teratogen, causing severe defects if the mother is infected in the first trimester. The protozoan parasite, Toxoplasma gondii, is usually acquired by ingesting undercooked meat or through cat feces. Its severity in the fetus is often inversely related to the timing of transmission, with earlier infection causing more significant harm.
Group B Streptococcus (GBS) and Escherichia coli are two of the most common bacteria implicated in ascending infections of the membranes and amniotic fluid. Listeria monocytogenes can cause severe fetal complications, including spontaneous abortion and stillbirth. Listeria is unique among bacteria in that it can use both the ascending and the hematogenous routes to reach the fetus.
Consequences for the Developing Fetus
The outcomes of intrauterine infection range from immediate, life-threatening complications to long-term developmental impairments. One of the most frequent consequences is preterm birth, with up to 70% of premature deliveries associated with IUI. The inflammatory response triggered by the infection releases signaling molecules called cytokines, which initiate the process of preterm labor.
The infection can also lead to fetal growth restriction (FGR) and, in the most severe cases, spontaneous abortion or stillbirth. Immediate concerns for the newborn include neonatal sepsis and organ-specific issues like pneumonia or meningitis. Parvovirus B19, for example, can cause severe fetal anemia and hydrops fetalis.
Long-term consequences are related to damage to the developing brain and sensory organs. Neurological impairments include cerebral palsy, microcephaly, and hearing loss, which is a common outcome of congenital CMV infection. Visual problems such as chorioretinitis are characteristic of infections like toxoplasmosis.
Diagnosis and Treatment Protocols
Diagnosing intrauterine infection involves a combination of maternal screening, clinical signs, and specialized prenatal testing. Routine prenatal care includes serological testing for many TORCH agents to determine the mother’s immunity status. For suspected acute infection, doctors look for clinical signs such as persistent maternal fever, an elevated fetal heart rate, and uterine tenderness.
When a bacterial infection of the amniotic fluid is suspected, a diagnostic amniocentesis may be performed to collect fluid for culture, Gram stain, or molecular testing. Fetal ultrasound imaging is another important tool, used to look for physical signs of fetal distress or organ damage, such as intracranial calcifications, an enlarged liver and spleen, or restricted growth. Postnatally, a newborn may undergo blood cultures and a physical examination to confirm the presence of an infection.
The management of IUI is guided by the type of pathogen and the severity of the infection. Bacterial infections, especially chorioamnionitis, are treated urgently with broad-spectrum intravenous antibiotics, often a combination of a beta-lactam and an aminoglycoside. Prompt delivery is typically required to resolve the infection, though the route of delivery is based on standard obstetric indications. While effective antiviral agents are limited for most congenital viral infections, supportive care, such as intrauterine blood transfusions for Parvovirus B19-induced anemia, can be administered.