Congenital infection

Congenital infection is a relatively rare, infectious intrauterine complication. Sometimes also called fetal infections due to pathogenesis – transplacental transmission from mother to fetus. The pathogen can be the cause of fetal demise, organ malformations, and preterm birth with its consequences; however, the pregnant woman is often asymptomatic. There are preventive measures against certain pathogens (rubeola – immunization; syphilis – antibiotics).

Types of infection in perinatology and neonatology

• congenital infections (e.g. TORCH)
• early-onset sepsis (EOS) => within 72 hours after birth
• late-onset sepsis (LOS) => after 72 hours of life

Pathogens causing Congenital infection

Cytomegalovirus (CMV)

• The most common pathogen causing congenital fetal infection
• CMV primary infection or reactivation of latent CMV
• Asymptomatic or multiple organ dysfunction syndrome (MODS) => encephalitis (microcephaly), exanthema, hepatosplenomegaly, chorioretinitis, thrombocytopenia
• Late morbidities: neurologic impairment, mental retardation, deafness, adverse neurodevelopment
• Ganciclovir (depends on the severity of infection and its consequences – irreversible organ changes)

Toxoplasma gondii

• With advancing gestation, the risk for infection increases; however the organ consequences are less severe
• Asymptomatic or multiple organ dysfunction syndrome (MODS) => encephalitis (microcephaly), hepatosplenomegaly, chorioretinitis
• Late morbidities: neurologic impairment, mental retardation, adverse neurodevelopment
• Spiramycin, Pyrimethamine

Treponema pallidum (lues, syphilis)

• Infection possible since 5^th month of pregnancy (maternal hematogenous dissemination)
• Asymptomatic or multiple organ dysfunction syndrome (MODS)
• Early form (< 2 years): asymptomatic, poor feeding, hemorrhagic rhinitis (coryza syphilitica), Parrot’s furrows (periorally), hepatosplenomegaly, skeletal abnormalities, pneumonia, pemphigus syphiliticus (bullous skin disorder)
• Late form: blunted upper incisor teeth (Hutchinson’s teeth), deafness (auditory nerve impairment), frontal bossing (prominence of the brow ridge), hard palate defect, interstitial keratitis (corneal inflammation), saber shins, saddle nose (collapse of the bony part of nose), swollen knees, short maxillae
• Hutchinson’s triad: teeth (notched incisors), keratitis, deafness (60-70% of cases)
• Penicillin

Parvovirus B19

• erythema infectiosum (5^th disease) in children and adults
• fetal anemia with hydrops (virus affects the red blood cell precursors in the bone marrow)
• No treatment

Rubella

• Congenital rubella syndrome (Gregg’s): sensorineural deafness, ophthalmologic abnormalities (retinopathy, cataract, glaucoma, microphthalmia), congenital heart defects (pulmonary stenosis, patent ductus arteriosus)
• Mandatory active immunization (MMR vaccine at 15 months of age – measles, mumps, and rubella)

Lyme disease (borreliosis)

• Borrelia burgdorferi sensu lato
• Early form: Clinical picture – MODS with high mortality
• Late form: adverse neurodevelopment with mental retardation, organ malformations
• Amoxicillin, Cefuroxime (doxycycline contraindicated in pregnancy)

Diagnosis

Clinical signs

• usually non-specific
• respiratory distress syndrome (RDS)
• apneas
• cyanosis
• circulation disturbances (tachycardia, poor perfusion, pale color)
• thermal instability
• petechiae
• neurologic symptoms (seizures, irritability, apathy, hypertonia/hypotonia)
• hyperbilirubinemia
• feeding intolerance, distended abdomen, vomiting, diarrhea

Laboratory findings

• inflammatory markers (C-reactive protein – CRP; procalcitonin – PCT, interleukin 6 – IL-6)
• full blood count (leucopenia/leucocytosis, shift to the left, I/T index > 0.2, anemia/thrombocytopenia)
• metabolism (hyperglycemia)
• blood gas (acidosis)
• cultures (blood culture, urine, cerebrospinal fluid, bronchoalveolar lavage)
• colonization (ear and nose, oropharynx, conjunctiva, rectum)
• serology (antibodies)
• PCR (cytomegalovirus – CMV)

Screening

• during pregnancy (syphilis – penicillin for seropositive women, hepatitis B – HBsAg, HIV)
• postnatally from the umbilical cord (serology tests for syphilis)
  → RPR = rapid plasma reagin = screening test for syphilis (cardiolipin [phospholipid] incorporated in the membrane of Treponema Pallidum reacts with antibodies)
  → TPHA= Treponema Pallidum hemagglutination = diagnostic test for syphilis (detects amount of anti-Treponema pallidum antibodies in the serum sample (umbilical cord) of a newborn)
• if seropositive mother (or unknown prenatal screening and care) was not treated optimally during pregnancy and the newborn has positive serology tests, the infant need to be covered with antibiotics (penicillin)

Prophylaxis

• congenital/perinatal infection: syphilis, group B Streptococcus (GBS), hepatitis B, herpes simplex virus, human immunodeficiency virus (HIV)
• postnatal infection: anti-epidemic guidelines for the neonatal intensive care unit (NICU) – hand hygiene before and after manipulation with a patient and his environment (equipment)

Therapy

General

• ventilation support (oxygen, nasal continuous positive airway pressure – CPAP, mechanical ventilation)
• circulation support (volume therapy, inotropes)
• immunoglobulins
• parenteral nutrition
• thermal management

Specific

• based on the pathogen
• broad-spectrum antibiotics => antibiotic rotation based on the clinical response and individual antimicrobial sensitivity of a pathogen
• antivirotics (aciclovir, ganciclovir)
• antimycotics (fluconazole, amphotericin B)

References

① Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017;390(10104):1770-1780. doi:10.1016/S0140-6736(17)31002-4