Ultrasound Findings in Fetal Infection No conflict of interest to report Kim A. Boggess MD Ob Gyn UNC at Chapel Hill Learning Objectives At conclusion, participants will Identify maternal infections that may present with ultrasound findings in the fetus; Recognize ultrasound findings that may indicate fetal infection; Identify clinical scenarios that indicate ultrasound screening for infection is appropriate Congenital Infection 5.2% of pregnancies complicated by viral infectious illness Infections account for 20% neonatal/fetal disease Fetal infection may have no maternal s/s Transplacental infection can occur Congenital infection Susceptible fetus Immature T-lymphocytes Low level IgM production Difficult diagnosis Reduced fetal protection Ultrasound suspicion with Multiple organ system anomalies IUGR Placental enlargement Abnormalities of amniotic fluid 1
Clinical Scenario 1 A 25y G1P0 elementary school nurse presents for care in the first trimester Do you screen her for any infections? If so, which ones? How do you screen for your infections of interest? Clinical Scenario You test her for CMV and Parvovivus and receive the following results: CMV IgM negative; IgG positive Parvo IgG positive What do you tell her about risk of fetal CMV or Parvovirus? Clinical Scenario 1 18 week ultrasound is normal CMV US findings Sensitivity: 30% specificity: 98% PPV:90% NPV: 70% CNS Ventriculomegally, intracranial calcifications, microcepahly Cardiomegaly Hepato-splenomegaly Hyperecohic bowel IUGR Hydrops Crino, 1999; Degani, 2006 CMV Ultrasound markers May occur later in pregnancy: >20-22 weeks Series of 19 culture positive (AF) 42% intracranial calcification 37% cardiac anomalies 32% parenchymal calcifications Intracranial calcification Classic lesion: Periventricular calcification Chronic: Microcephaly Hydrocepahlus Glial encephalomyelitis in periventricular location porencphaly Degani, 2006 Ob/Gyn Survey 2
Chorioretinits, cataract, microphthalmia Calcification of retina, choroids Placental calcification Villous destruction, inflammation Focal necrosis Hemorrhage Hepatic calcification Hepatic dysfunction Altered DV doppler Response to hypoxia and/or myocardial impairment Major US findings Microcephaly Hydrocephaly Calcification of: Placenta Liver Periventricular area Retina CMV Maternal diagnosis: Maternal IgG, IgM IgG + with prior negative = primary infection IgM +, IgG + IgG avidity test or anti-cmv glycoprotein B IgG avidity >50-65% in first trimester rare congenital infection Fetal diagnosis 7 weeks after seropositivity/ after 21 wk EGA AF CMV culture, PCR, shell viral assay similar prediction Viral load/presence/ IgM in cord blood limited prognostic value 3
CMV Primary CMV CMV IgM + IgG + IgG - 100 women with Primary CMV Avidity Test Repeat 2 weeks 60 non infected infants 40 infected Medium/High Low IgG + IgG - Nonspecific IgM 36 asymp 4 symp Infection > 1.5 mo Suspect primary infection Suspect primary infection Prenatal diagnosis 31 remain asymp 5 with long term sequelae 4 with sequelae Amniotic fluid > 21 wks viral isolation, shell vial assay PCR Screening for CMV Universal screening not recommended ACOG, SOCG Serologic testing of suspected maternal infection in pregnancy appropriate CMV IgG/IgM/Avidity Serologic monitoring of high risk groups reasonable in pregnancy CMV IgG at intake, repeat 18-20 weeks Child < 4 years of age in daycare Maternal at-risk occupation CMV Summary Pearls? Screening High risk groups at intake, repeat 18-20 weeks EGA Prevention measures CMV IgG add avidity Seroconversion offer PDx > 6 weeks, >21 weeks EGA Maternal serology For exposure / maternal s/s IgM, IgG if positive IgG avidity or serial testing Fetal US findings concerning for CMV Maternal serology misleading Amniocentesis for diagnosis CMV-Patient Questions Clinical Scenario 2 Should I be screened for CMV? How will info help; what if IgM +? I had primary CMV during pregnancy. Should I terminate? Fetal risk depends in in-utero symptoms. Counsel and offer prenatal diagnosis How/when can fetal infection be diagnosed? > 21 wks, 6-9 weeks after maternal diagnosis Can I breastfeed if I have CMV? Transmission possible, risk low, serious infection unlikely At 24 weeks patient visits her in-laws. While there her MIL breaks out in a rash; it is vesicular and only on her scalp. She has close contact with the rash, examining it to try and determine what it is. They finally go to PCP, who diagnoses shingles. 4
Clinical Scenario 2 What if anything do you do for your patient? She denies history of varicella You check titers and they are negative, indicative of no varicella immunity You do an ultrasound Varicella Highly infectious via respiratory droplets 1-20% - fetal infection with maternal infection Congenital varicella syndrome 0.4% (347, 59% with infection <20 weeks) Harger, Obstet Gynec 2002 Latency between maternal infection and US findings = 5-19 weeks Varicella Transmissibility of virus with shingles Risk of primary infection for mother Varicella Ultrasound Ventriculmegaly, intracranial calcifications Congenital cataract, microphthalmos Hepatomegaly, ascites, parenchymal cysts Small placenta IUGR, limb deformities (skin scars), hydrops Clinical findings after first trimester infection IUGR, skin scarring, limb deformities, eye abnormalities Congenital Varicella Ultrasound Microcephaly Retinal calcifications Hepatosplenomegaly Limb deformities IUGR Clinical Scenario 2 You see liver calcifications and fetal biometry lagging by 3 weeks You offer what tests, if any 5
Congenital Varicella Diagnosis Amniotic fluid Viral culture PCR more sensitive PUBS for IgM not useful OTHER INFECTIONS HSV Fetal infection 1% of pregnant women with symptomatic infection Increased risk with primary maternal infection Transplacental passage of maternal Ab protective against perinatal infection HSV Ultrasound (similar to CMV) Hydranencephaly, ventriculomegaly, intracranial calcifications (periventricular) Microcephaly Hepato-splenomegaly, hyperechoic bowel IUGR, limb deformities Degani, 2006; Rubella Epidemic 1964 > 12 million cases 2100 neonatal deaths 20,000 CRS > 11,000 deaf > 3500 blind 1800 MR Congenital Rubella Syndrome SAB Fetal infection Risk varies by gestational age 1st trimester: 80% 2nd trimester: 25% 3rd trimester: 100% if > 36 w Fetal growth restriction Stillbirth Congenital defects 6
Congenital Rubella Syndrome Rubella Exposure CRS limited to infection < 16 weeks Deafness Cataracts Heart defects Microcephaly MR Liver, spleen damage Rubella Exposure Test maternal IgG/IgM IgM+/IgG+ Test IgG avidity Low Medium Recent Primary Inconclusive IgG+ Past Infection IMMUNE High Past infection OR IgG- Susceptible Test Q Month Until 16 weeks IgM- IgM+/IgG- Suspect Primary Infection Repeat on convalescent serum IgM+/IgG- IgM+/IgG+ Nonspecific IgM Primary Infection Repeat on 2nd sample Reinfection Rubella-Patient Questions Clinical Scenario 3 I have rubella. Should I terminate Risk depends on trimester. Counsel and offer prenatal diagnosis What in-utero therapy exists for rubella? None I received vaccine in first trimester. Now what? Does vaccine cause CRS? No, but virus can be detected in fetus/placenta I am nonimmune and need vaccine. Can I breastfeed? Yes Clinical Scenario 3 Echogenic bowel Bright as bone Consider transducer frequency 5 MHz or lower 7
Echogenic Bowel Differential Bowel vs. extraintestinal Blood Aneuploidy 3-25% (70% Tri 21) Cystic fibrosis 3% Infection (least common cause; CMV, toxo, parvo/vzv/hsv) Bowel obstruction QUESTION OR COMMENTS 8