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Case Presentation 1

Case Presentation 1. Mom: 22 years old, primigravida with normal pregnancy except URI in 1 st trimester Premature labor at 32 weeks gestation Delivered normal premature neonate Baby started having respiratory distress soon after birth Baby resuscitated, intubated and ventilated.

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Case Presentation 1

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  1. Case Presentation 1 • Mom: 22 years old, primigravida with normal pregnancy except URI in 1st trimester • Premature labor at 32 weeks gestation • Delivered normal premature neonate • Baby started having respiratory distress soon after birth • Baby resuscitated, intubated and ventilated

  2. Physical examination Sick looking neonate H.R. 170/min R.R. 60/min Temp 36˚C BP 30/p Petechiae/purpura HSM Investigation Hgb 110 g/l Platelets 35,000 WBC 14.0; 70% PMN & 8% Bands Case Presentation 1

  3. Congenital Infections Rupesh Chawla MD MSc FRCPC Pediatric Infectious Diseases Resident Rounds April 22, 2010

  4. Thank you to Dr. Taj Jadavji, Dr. Ameeta Singh, and Dr. Charles G. Prober for use of slides and information

  5. Definitions • Congenital • Infection acquired in utero prior to the onset of labor and delivery. • eg. CMV, Rubella, VZV, Toxo, Syphillis, Parvo • Perinatal • Infection acquired just before, during or after the onset of labor. • eg. HIV, HSV, HBV, GBS, Listeria, E.Coli, TB

  6. Unsual Suspects… • TORCH • T…Toxoplasma • O…Other • R…Rubella • C…Cytomegalovirus (CMV) • H…Herpes Simplex Virus • Now TORCHS or STORCH • Need to remember SYPHILIS!!!

  7. Congenital Infections:Pathogenesis • Maternal infection • Primary vs recurrent • Timing of gestational infection • Early vs late • Mode of acquisition • Transplacental vs other • Congenital vs perinatal

  8. Congenital Infections:Incidence in the United States

  9. Number of Neonates With Symptoms at Birth is Small

  10. Congenital Infections:Common Manifestations • Prematurity • Intrauterine Growth Retardation (IUGR) • Congenital Defects • Signs suggestive of active infection

  11. Congenital Infections:Common Manifestations • Congenital Defects • Abnormal head size • Intracranial calcifications • Eye abnormalities • Hearing loss

  12. Congenital Infections:Abnormal Head Size • Microcephaly • CMV • Rubella • Toxoplasmosis • Hydrocephalus • Toxoplasmosis • Syphilis • CMV

  13. Congenital Infections:Intraventricular Calcifications • Periventricular: CMV • Diffuse: Toxoplasmosis • Rare: Rubella, HSV

  14. Cataracts Rubella Chorioretinitis Rubella CMV Toxoplasmosis Syphilis VZV HSV Congenital Infections:Eye Abnormalities

  15. Congenital Cataracts • Congenital Rubella • Galactosemia • Pierre Robin syndrome • Oculocerebrorenal syndrome • Oculomandibulofacial syndrome • Heredity

  16. Congenital Infections:Hearing Loss • CMV: 5-10% of infected infants; most common infectious cause of hearing loss • Rubella: common manifestation of infection • Toxoplasmosis: ~25% of untreated infants • Syphilis: late (> 2 years) manifestation of infection

  17. Congenital Infections:Signs Suggestive of Active Infection • Jaundice • Hepatosplenomegaly/ hepatitis • Thrombocytopenia/ anemia • Rash • CSF inflammation • Bone lesions • Pneumonitis

  18. Congenital Syphilis

  19. Incidence of Syphilis, USA • Decrease in # of cases of primary and secondary syphilis during last decade • 2002, ~1.1 cases per 100,000 women • Parallel decrease in # cases of congenital syphilis • However, in Alberta…

  20. Summary of 9 congenital syphilis cases, Alberta 2005-6 • First 2005 case diagnosed February 2005: 5 cases in 2005 and 3 in 2006 • 8 cases born in Edmonton, 1 in Calgary • 4 mothers did not access antenatal care till delivery (not tested for syphilis till delivery); 1 tested 2nd trimester and lost to follow-up, 4 tested negative earlier in pregnancy • 1 neonatal death; other babies severely affected and required hospitalization

  21. Gestational Syphilis:Risk Factors • Crack cocaine • HIV infection • Poor or no prenatal care • Unmarried or teenaged mother • Disadvantaged minorities • History of STDs • Sexual promiscuity

  22. Gestational Syphilis:Consequences • Rates of vertical transmission: 70-100% for primary and secondary syphilis, 40% for early latent disease, and 10% for late latent disease • Transmission greatest during second half of gestation • Infection may result in abortion, stillbirth, prematurity, perinatal death, or congenital infection Watson Jones D et al. J Infect Dis. 2002;186:940-7

  23. Gestational Syphilis:Early Manifestations • Persistent rhinitis (sniffles) • Rash • Hepatosplenomegaly • Bone lesions • Lymphadenopathy • Pneumonia • CSF abnormalities • Glomerulonephritis

  24. Gestational Syphilis:Late (>2 Years) Manifestations • Hutchinson’s triad • Interstitial keratitis • Peg-shaped upper incisors • Eighth nerve deafness • Frontal bossing • Saddle nose • Saber shins • Mental retardation • Clutton’s joints

  25. Congenital Syphilis:Case Definition • Confirmed: • Treponema pallidum identified by isolation (rabbit infectivity test), dark field microscopy, or stains from lesions, placenta, umbilical cord, amniotic fluid, or autopsy

  26. Congenital Syphilis:Case Definition • Presumptive • Untreated or inadequately treated mother • Any infant with a reactive treponemal test + • Evidence of congenital syphilis on exam • Evidence of congenital syphilis on long bone radiograph • Reactive CSF VDRL • Elevated CSF protein or cell count • Non-treponemal titer 4-fold higher than mother’s Pickering LK, ed. Red Book 2009

  27. Congenital Syphilis:Evaluation of the Newborn • Quantitative nontreponemal testing of all infants born to seropositive mothers • Additional testing (CSF, CBC, LFTs, radiographs) if: • Mother was untreated, inadequately treated* or treatment was not documented • Mother was treated but a 4-fold decrease in titer was not observed * Inadequate dosage, non-penicillin regimen, <1 month prior to delivery

  28. Congenital Syphilis:Serologic Testing • Quantitative nontreponemal test • RPR • VDRL (CSF only in Canada) • Treponemal tests • FTA-ABS, • MHA-TP • EIA • INNO-LIA • Antitreponemal IgM • 20-40% false (-); 10% false (+)

  29. Congenital Syphilis:Management • If in doubt about: • Maternal therapy • Extent of neonatal infection • Likelihood of follow-up • Treat infant: • Aqueous crystalline penicillin G (IV) • 100,000-150,000 U/kg/day x 10

  30. Toxoplasmosis • Infection rate lowest in early pregnancy (15-30%) • Outcome poor (still birth, hydrops, preterm birth) • 40% of infections severe • 35% stillborns, neonatal deaths • Infection rate higher in late pregnancy (60%) • 90% sub-clinical • 10% mild

  31. Toxoplasmosis • Signs and symptoms (25%) of Toxoplasmosis in the Newborn • Chorioretinitis 85% • Intracranial calcification 35% • Hydrocephalus 20% • Others – anemia, jaundice, hepatosplenomegaly, seizures, fever, lymphadenopathy, microcephaly, eosinophilia, rash, pneumonia, bony defects, endocrine abnormalities

  32. Toxoplasmosis DIAGNOSIS AND TREATMENT • Physical exam (eye) • CBC, Platelets, LFTs • Maternal, Infant sera for antibodies • High lgG levels • Infant: positive lgM, PCR (blood, CSF) • Treatment • Pyrimethamine+Sulfadiazine+Leucovorin duration unknown; usually 1 yr • Prednisone if CSF protein >1 g/dl or if vision threatened McLeod R et al. Clin Infect Dis 2006;15:1395-7

  33. Congenital Rubella Syndrome • Risk to the fetus varies depend on gestational age • 1 – 4 weeks 80% • 5 – 9 weeks 30% • 10 - 14 weeks 8% • Congenital heart disease (PDA, VSD, PS, CoAo), deafness, cataract, glaucoma, microcephaly, chorioretinitis, hepatosplenomegaly, purpura, mental retardation • Prevented by widespread use of Rubella Vaccine • No evidence of waning immunity after vaccination • Diagnosis: physical exam, PCR, Rising antibody titers (lgG, lgM)

  34. Cytomegalovirus (CMV) EPIDEMIOLOGY • Leading cause of congenital infection • 0.2 to 2.5% newborns are congenitally infected • 90% of congenitally infected newborns are asymptomatic at birth • The most useful predictor of adverse neuro-developmental outcome is abnormal neuro-imaging in the newborn

  35. Cytomegalovirus (CMV) EPIDEMIOLOGY • 10% of CMV seropositive woman excrete CMV from the genital tract at delivery • 10% - 27% of post partum women excrete CMV in breast milk • Congenital infected babies excrete virus intermittently for many months

  36. Cytomegalovirus (CMV) EPIDEMIOLOGY • In Canada 2000 newborn are born with congenital CMV infections • 1800 Asymptomatic • About 10% develop long term sequelae • 200 Symptomatic • - 12% die as neonates • About 60% develop long term sequelae • Most common sequelae • S-N hearing loss • Developmental delay

  37. Cytomegalovirus (CMV) EPIDEMIOLOGY • Intrauterine transmission is 5 times more likely when mother has a primary infection (40%) in pregnancy then a secondary infection (8%) • Primary maternal infection is more likely to cause severe disease in the baby • Daycare is associated with transmission to children, staff • Fetal infection can occur after primary or secondary infection

  38. Cytomegalovirus (CMV) • Effect on mother • Minimal • “flu like illness”

  39. Cytomegalovirus (CMV) EFFECT ON FETUS • Majority Asymptomatic • Microcephaly • Intrauterine Growth Retardation • Hepatosplenomegaly • Chorioretinitis • Cranial Calcification • S-N hearing loss • Thrombocytopenia with petechiae

  40. Cytomegalovirus (CMV) • Virus isolation from saliva/urine within 3 weeks of birth • Positive culture later include perinatal infection • PCR (urine, saliva, buffy coat) • More sensitive than culture • Positive PCR in CSF suggests CNS damage • Antibody titers (Serology) • Maternal: may be useful if known before pregnancy • Routine screening controversial • Infant: Rising titers indicate infection not necessarily disease

  41. 181 pregnant women identified with confirmed primary CMV infection 79 underwent amnio- centesis before or at enrolment & >6 wk after maternal seroconversion • 102 enrolled who did not • undergo amniocentesis • 1˚ infection < 6 weeks • <20 wks gestation • Refused to undergo • amniocentesis 55 women with CMV-positive amniotic fluid enrolled 24 women with CMV-negative amniotic fluid ineligible 37 elected to receive hyperimmune globulin (100 U/kg) monthly until delivery 65 elected not to receive hyperimmune globulin Passive Immunization During Pregnancy for Congenital CMV InfectionProspective Non-Randomized Study Therapy Group Prevention Group Infants evaluated at birth Nigro et al, N Engl J Med 2005; 353:1350-62

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