3 You are taking care of a term newborn male with birth weight/length <10th %ile. Physical exam is normal except for a slightly enlarged liver span. A CBC is significant for low platelets.What, if anything, do you worry about?How do you proceed with a work-up?
4 Index of Suspicion When do you think of TORCH infections? IUGR infants HSMThrombocytopeniaUnusual rashConcerning maternal history“Classic” findings of any specific infection
5 Diagnosing TORCH Infection !!!!!!DO NOT USE TORCH TITERS!!!!!!
6 Diagnosing TORCH Infection Good maternal/prenatal historyRemember most infections of concern are mild illnesses often unrecognizedThorough exam of infantDirected labs/studies based on most likely diagnosis…Again, DO NOT USE TORCH TITERS!
7 Screening TORCH Infections Retrospective study of 75/182 infants with IUGR who were screened for TORCH infections1/75 with clinical findings, 11/75 with abnl lab findingsAll patients screened:TORCH titers, urine CMV culture, head USOnly 3 diagnosed with infectionNONE by TORCH titer!!Overall cost of all tests = $51,715“Shotgun” screening approach NOT cost effective nor particularly usefulDiagnostic work-up should be logical and directed by history/exam findingsKhan, NA, Kazzi, SN. Yield and costs of screening growth-retarded infants for torch infections. Am J Perinatol 2000; 17:131.
8 Toxoplasmosis Caused by protozoan – Toxoplasma gondii Domestic cat is the definitive host with infections via:Ingestion of cysts (meats, garden products)Contact with oocysts in fecesMuch higher prevalence of infection in European countries (ie France, Greece)Acute infection usually asymptomatic1/3 risk of fetal infection with primary maternal infection in pregnancyInfection rate higher with infxn in 3rd trimesterFetal death higher with infxn in 1st trimester
9 Clinical Manifestations Most (70-90%) are asymptomatic at birthClassic triad of symptoms:ChorioretinitisHydrocephalusIntracranial calcificationsOther symptoms include fever, rash, HSM, microcephaly, seizures, jaundice, thrombocytopenia, lymphadenopathyInitially asymptomatic infants are still at high risk of developing abnormalities, especially chorioretinitis
11 Diagnosis Maternal IgG testing indicates past infection (but when…?) Can be isolated in culture from placenta, umbilical cord, infant serumPCR testing on WBC, CSF, placentaNot standardizedNewborn serologies with IgM/IgA
12 Toxo ScreeningPrenatal testing with varied sensitivity not useful for screeningNeonatal screening with IgM testing implemented in some areasIdentifies infected asymptomatic infants who may benefit from therapy
13 Prevention and Treatment Treatment for pregnant mothers diagnosed with acute toxoSpiramycin dailyMacrolide antibioticSmall studies have shown this reduces likelihood of congenital transmission (up to 50%)If infant diagnosed prenatally, treat momSpiramycin, pyrimethamine (anti-malarial, dihydrofolate reductase inhib), and sulfadiazine (sulfa antibiotic)Leucovorin rescue with pyrimethamineSymptomatic infantsPyrimethamine (with leucovorin rescue) and sulfadiazineTreatment for 12 months totalAsymptomatic infantsCourse of same medicationsImproved neurologic and developmental outcomes demonstrated (compared to untreated pts or those treated for only one month)
14 Syphilis Treponema pallidum (spirochete) Transmitted via sexual contactPlacental transmission as early as 6wks gestationTypically occurs during second halfMom with primary or secondary syphilis more likely to transmit than latent diseaseLarge decrease in congenital syphilis since late 1990sIn 2002, only 11.2 cases/100,000 live births reported
17 Congenital Syphilis2/3 of affected live-born infants are asymptomatic at birthClinical symptoms split into early or late (2 years is cutoff)3 major classifications:Fetal effectsEarly effectsLate effects
18 Clinical Manifestations Fetal:StillbirthNeonatal deathHydrops fetalisIntrauterine death in 25%Perinatal mortality in 25-30% if untreated
19 Clinical Manifestations Early congenital (typically 1st 5 weeks):Cutaneous lesions (palms/soles)HSMJaundiceAnemiaSnufflesPeriostitis and metaphysial dystrophyFunisitis (umbilical cord vasculitis)
20 Periostitis of long bones seen in neonatal syphilis
21 Clinical Manifestations Late congenital:Frontal bossingShort maxillaHigh palatal archHutchinson teeth8th nerve deafnessSaddle nosePerioral fissuresCan be prevented with appropriate treatment
22 Hutchinson teeth – late result of congenital syphilis
23 Diagnosing Syphilis (Not in Newborns) Available serologic testingRPR/VDRL: nontreponemal testSensitive but NOT specificQuantitative, so can follow to determine disease activity and treatment responseMHA-TP/FTA-ABS: specific treponemal testUsed for confirmatory testingQualitative, once positive always positiveRPR/VDRL screen in ALL pregnant women early in pregnancy and at time of birthThis is easily treated!!
24 CDC Definition of Congenital Syphilis Confirmed if T. pallidum identified in skin lesions, placenta, umbilical cord, or at autopsyPresumptive diagnosis if any of:Physical exam findingsCSF findings (positive VDRL)Osteitis on long bone x-raysFunisitis (“barber shop pole” umbilical cord)RPR/VDRL >4 times maternal testPositive IgM antibody
25 Diagnosing Congenital Syphilis IgG can represent maternal antibody, not infant infectionThis is VERY intricate and often confusingConsult your RedBook (or peds ID folks) when faced with this situation
26 TreatmentPenicillin G is THE drug of choice for ALL syphilis infectionsMaternal treatment during pregnancy very effective (overall 98% success)Treat newborn if:They meet CDC diagnostic criteriaMom was treated <4wks before deliveryMom treated with non-PCN medMaternal titers do not show adequate response (less than 4-fold decline)
27 Rubella Single-stranded RNA virus Vaccine-preventable disease No longer considered endemic in the U.S.Mild, self-limiting illnessInfection earlier in pregnancy has a higher probability of affected infant
29 Clinical Manifestations Sensorineural hearing loss (50-75%)Cataracts and glaucoma (20-50%)Cardiac malformations (20-50%)Neurologic (10-20%)Others to include growth retardation, bone disease, HSM, thrombocytopenia, “blueberry muffin” lesions
31 DiagnosisMaternal IgG may represent immunization or past infection - Useless!Can isolate virus from nasal secretionsLess frequently from throat, blood, urine, CSFSerologic testingIgM = recent postnatal or congenital infectionRising monthly IgG titers suggest congenital infectionDiagnosis after 1 year of age difficult to establish
32 Treatment Prevention…immunize, immunize, immunize! Supportive care only with parent education
33 Cytomegalovirus (CMV) Most common congenital viral infection~40,000 infants per year in the U.S.Mild, self limiting illnessTransmission can occur with primary infection or reactivation of virus40% risk of transmission in primary infxnStudies suggest increased risk of transmission later in pregnancyHowever, more severe sequalae associated with earlier acquisition
34 Clinical Manifestations 90% are asymptomatic at birth!Up to 15% develop symptoms later, notably sensorineural hearing lossSymptomatic infectionSGA, HSM, petechiae, jaundice, chorioretinitis, periventricular calcifications, neurological deficits>80% develop long term complicationsHearing loss, vision impairment, developmental delay
35 Ventriculomegaly and calcifications of congenital CMV
36 Diagnosis Maternal IgG shows only past infection Infection common – this is uselessViral isolation from urine or saliva in 1st 3weeks of lifeAfterwards may represent post-natal infectionViral load and DNA copies can be assessed by PCRLess useful for diagnosis, but helps in following viral activity in patientSerologies not helpful given high antibody in population
37 Treatment Ganciclovir x6wks in symptomatic infants Studies show improvement or no progression of hearing loss at 6mosNo other outcomes evaluated (development, etc.)Neutropenia often leads to cessation of therapyTreatment currently not recommended in asymptomatic infants due to side effectsArea of active research to include use of valgancyclovir, treating asx patients, etc.
38 Herpes Simplex (HSV) HSV1 or HSV2 Primarily transmitted through infected maternal genital tractRationale for C-section delivery prior to membrane rupturePrimary infection with greater transmission risk than reactivation
39 Clinical Manifestations Most are asymptomatic at birth3 patterns of ~ equal frequency with symptoms between birth and 4wks:Skin, eyes, mouth (SEM)CNS diseaseDisseminated disease (present earliest)Initial manifestations very nonspecific with skin lesions NOT necessarily present
41 Diagnosis Culture of maternal lesions if present at delivery Cultures in infant:Skin lesions, oro/nasopharynx, eyes, urine, blood, rectum/stool, CSFCSF PCRSerologies again not helpful given high prevalence of HSV antibodies in population
42 Treatment High dose acyclovir 60mg/kg/day divided q8hrs X21days for disseminated, CNS diseaseX14days for SEMOcular involvement requires topical therapy as well
44 Which TORCH Infection Presents With… Snuffles?syphilisChorioretinitis, hydrocephalus, and intracranial calcifications?toxoBlueberry muffin lesions?rubellaPeriventricular calcifications?CMVNo symptoms?All of them
45 Which TORCH Infections Can Absolutely Be Prevented? RubellaSyphilis
46 When Are TORCH Titers Helpful in Diagnosing Congenital Infection? NEVER!