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Congenital and Perinatal Infection

Congenital and Perinatal Infection. Congenital Infections: Presentation. Intrauterine growth retardation Microcephaly Hydrocephalus Intracranial calcifications Thrombocytopenia Blueberry muffin skin rash Hepatosplenomegaly, conjugated hyperbilirubinemia Chorioretinitis Cataracts.

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Congenital and Perinatal Infection

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  1. Congenital and Perinatal Infection

  2. Congenital Infections: Presentation • Intrauterine growth retardation • Microcephaly • Hydrocephalus • Intracranial calcifications • Thrombocytopenia • Blueberry muffin skin rash • Hepatosplenomegaly, conjugated hyperbilirubinemia • Chorioretinitis • Cataracts

  3. Blueberry Muffin Skin Rash

  4. Etiologies of Congenital Infection • Toxoplasmosis T • Syphilis Other • Rubella R • Cytomegalovirus C • Herpes simplex H • HIV • Lymphocytic choriomeningitis virus • Parvovirus B19 • Varicella

  5. Diagnosis of Congenital Infection:General Tests • CBC • Total/direct bilirubin, liver enzymes • Total IgM • Bone radiographs • CSF exam • Eye exam • CNS imaging

  6. Diagnosis of Congenital Infection:Specific Tests • Toxoplasmosis IgM, IgG • RPR • Rubella IgM • Rubella culture: eye, urine, nasopharynx • Urine culture for CMV • Herpes simplex IgM, IgG • CSF: routine studies, quantitative VDRL, HSV PCR • Parvovirus B19 PCR • Lymphocytic choriomeningitis virus: infant IgM and IgG, mother IgG

  7. How Toxoplasmosis is Transmitted

  8. Toxoplasmosis • Toxoplasma gondii, protozoan, cats are host • 70-90% asymptomatic • Symptoms: maculopapular rash, thrombocytopenia, lymphadenopathy, hepatomegaly, splenomegaly, jaundice, hydrocephalus, microcephaly, chorioretinitis, seizures, deafness • Diagnosis: IgM, IgG, intracranial calcifications • Treatment: pyrimethamine, sulfadiazine

  9. Toxoplasmosis: Chorioretinitis

  10. Congenital Syphilis: Symptoms • Asymptomatic 50% • Fever, lymphadenopathy, irritability, failure to thrive • Jaundice, hepatosplenomegaly • Mucocutaneous: palmar/plantar bullae, maculopapular rash trunk/limbs, mucosal lesions, condylomata lata • Anemia (BM arrest, hemolysis), thrombocytopenia, low/high WBCs • Meningitis • “Snuffles” (serous rhinitis) • Bone changes: osteochondritis of humerus, tibia

  11. Congenital Syphilis: Snuffles

  12. Congenital Syphilis: Diagnostic Studies • Quantitative RPR • CSF exam: cell count, protein, VDRL • CBC, platelets, liver enzymes • Long bone radiographs • Demonstration of spirochetes: tissue/fluid • HIV testing

  13. Congenital Syphilis: Bone Changes

  14. Congenital Syphilis: Treatment and Follow-up of the Newborn • Choice of regimens for confirmed or probable congenital syphilis: • Penicillin G 100-150,000 unit/kg/day x 10-14 days (50,000 unit/kg/dose IV BID x 7 days, then TID for a total of 10 days) • Procaine penicillin G 50,000 unit/kg/day IM once daily x 10 days (may not adequately treat CNS) • ampicillin is not a suitable alternative • RPR at 3, 6, 12 months • Complicated cases should be referred to specialist

  15. Congenital Rubella: Clinical Findings • Asymptomatic: 50% at birth • Sensorineural hearing loss • Mental retardation • PDA, peripheral pulmonic stenosis • Ocular: cataracts, chorioretinitis, glaucoma • Microcephaly • Blueberry muffin rash • Metaphyseal radiolucencies

  16. Congenital Rubella: Vertical Transmission • Transplacental passage of virus • Greatest risk for congenital defects and hearing loss early in the pregnancy • Non-immune pregnant women • do not immunize during pregnancy • no cases of malformation due to rubella vaccine in women immunized during pregnancy • avoid exposure to rubella • post-partum vaccine

  17. Congenital Rubella: skin Lesions

  18. Congenital Rubella Syndrome

  19. Congenital Rubella: Diagnosis and Treatment • Diagnosis: • Rubella specific IgM • culture: nasopharynx, blood, urine, CSF, throat • Treatment: supportive

  20. Cytomegalovirus: Transmission • Vertical transmission • transplacental and perinatal acquisition • maternal primary and reactivated CMV • Incidence: • 2.5% • most are asymptomatic - 95%

  21. Cytomegalovirus: Clinical Findings In Symptomatic Infants • Microcephaly, intracranial calcifications • Thrombocytopenia, petechiae, purpura • Conjugated hyperbilirubinemia, elevated liver enzymes, liver failure • Interstitial pneumonitis • Hearing loss • Mental retardation • Neurologic impairment, cerebral palsy • Chorioretinitis • Intestinal pseudo-obstruction like illness

  22. CMV: Calcifications

  23. CMV: Hydrocephalus, Calcifications

  24. Cytomegalovirus: Diagnosis • CMV titers: • IgM, IgG • Acute and convalescent • Urine culture for CMV • Excretion may be intermittent • CNS imaging • Eye exam

  25. Cytomegalovirus: Treatment • Supportive • Platelet transfusion • Anti-viral treatment • Ganciclovir may reduce sequelae, but of limited efficacy • CMV hyperimmune globulin • Infectious disease consultation

  26. Lymphocytic choriomeningitis virus • Arenavirus, shed by rodents • Symptoms in adults: influenza like illness - fever, malaise, myalgia, retro-orbital headache, photophobia • Congenital infection: hydrocephalus, chorioretinitis, intracranial calcifications, microcephaly, mental retardation, neurologic sequelae, visual loss • Diagnosis: culture, acute and convalescent titers • Treatment: supportive

  27. Lymphocytic Choriomeningitis Virus - Hydrocephalus

  28. Parvovirus B19 • Associated with multiple disorders: • Erythema infectiosum (fifth disease) • Aplastic crisis (hemolytic disorders, sickle cell) • Chronic anemia in immunosuppressed • Acute arthritis • Fetal hydrops and death due to anemia • (?)Efficacy of intrauterine transfusion • Spontaneous recovery of fetal hydrops can occur

  29. Varicella • Maternal varicella before 20 weeks: congenital anomalies reported to be 1-2% • Cicatricial skin lesions • Limb hypoplasia • CNS, ocular, neurologic • Maternal varicella in last 5 days of pregnancy to 2 days post partum: • VZIG 125 units IM indicated in exposed infants • Skin lesions, pneumonitis, dissemination reported • Add acyclovir if signs or symptoms develop

  30. Congenital varicella

  31. Varicella: perinatally acquired

  32. Perinatally Acquired Infection: Basic Principles • Maternal colonization or infection: • Amniotic fluid • Blood • Genital tract secretions • Breast milk • Direct skin contact, environment • Timing and duration of exposure • Interventions, prophylaxis

  33. Herpes Simplex: Epidemiology • Vertical transmission most common • perinatal exposure with ROM and delivery • 50% risk if infant exposed to primary maternal HSV • <1-5% risk if infant exposed to recurrent maternal HSV • increased risk in premature infants (reduced IgG) • C-section reduces risk if ROM < 4-6 hour • Horizontal transmission reported • nursery outbreaks • Time of onset: 2 days - several weeks

  34. Herpes Simplex: Clinical Presentation • Fever • skin vesicles • encephalitis • seizures • respiratory distress, pneumonia • hepatitis • septic shock like syndrome

  35. Herpes Simplex Skin Lesions

  36. Herpes Simplex Skin Lesions

  37. Herpes Simplex Skin Lesions

  38. Herpes Simplex Conjunctivitis

  39. Herpes Simplex Oral Lesions

  40. Herpes Simplex: Encephalitis

  41. Neonatal Herpes Simplex: Treatment • Acyclovir 60 mg/kg/day divided q 8 hr x 14 days (21 days for systemic or CNS) • Ocular HSV: add ophthalmic trifluridine, iododeoxyuridine, or vidarabine • Supportive: control seizures, respiratory and cardiovascular support • Reduce cutaneous or ocular spread • High mortality rate for CNS or systemic HSV, even with treatment

  42. Management of HSV Exposure • Recurrent maternal HSV • risk is very low; observation only • Primary maternal disease • risk is high • viral throat culture at 24-48 hr of age • empiric therapy is controversial • Premature infant - risk may be greater

  43. HIV • Transmission is vertical • In utero, intrapartum (most common), and postnatal (breastfeeding) • Risk factors

  44. Zidovudine (AZT) for reduction of perinatal HIV transmission • pregnancy: begin 200 mg PO 3x/day at 14-34 wk, continue throughout pregnancy • intrapartum: 2 mg/kg x 1 h, then 1 mg/kg/h IV until delivery • newborn: 2 mg/kg 4x/day PO begining at 8-12 h of age until 6 weeks of age • referral to pediatric HIV center

  45. HIV: perinatal prophylaxis • Reduction of vertical transmission with AZT as compared to placebo in women with mildly symptomatic disease • Connor EM et al. NEMJ 1994;331:1173 • placebo 25.5% • prenatal, intrapartum, postnatal 8.3%

  46. HIV: Benefit persists even with abbreviated prophylaxis • DNA PCR on HIV exposed infants with incomplete prophylaxis. • Wade NA et al. NEJM 1998;339:1409 • prenatal 6.1% • intrapartum 10.0% • < 48 h postnatal 9.3% • > 48 h postnatal 18.4%

  47. HIV: mode of delivery • Metanalysis of 15 NA/European studies • 8533 mother-child pairs • adjusted for antiretroviral Rx, maternal stage of disease and birth weight • elective C-section: prior to labor or ROM • International Perinatal HIV Group • NEJM 1999;340:977

  48. HIV: mode of delivery • other mode (vag, non-elective C/S) 16.7% • elective C-section 8.4% • other mode, complete retroviral Rx 7.3% • elective C/S, complete retroviral Rx 2.0% • International Perinatal HIV Group • NEJM 1999;340:977

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