INFECTION IN PREGNANCY

TORCH

Horizontal transmission

Vertical transmission

Congenital infection

Perinatal infection

Neonatal infection

Postnatal infection

Mode of Transmission

Infection during pregnancy:

Transplacental infection

Non placental infection:

Ascending infection

Intrapartum infection

Postnatal infection

General Principles

Pregnancy does not alter resistance to infection

Severe infections have greater effects on the fetus

Maternal antibodies cross the placenta and give passive immunity to the fetus

Fetus becomes immunologically competent from the 14th week

Fetus and Infection

Indirect effect - O2 transport, nutrient exchangeDirect effect - invasion of placenta and infection of fetusViruses more than bacteriararely effect fetus unless maternal infection is severeexception: Rubella, CMV, Herpes Simplex

Fetus and Infection

Infections cause

- miscarriage

- congenital anomalies

- fetal hydrops

- fetal death

- preterm delivery

- preterm rupture of the membranes

TORCH

T = Toxoplasma gondii

O= Others

R= Rubella Virus

C= Cytomegalovirus

H= Herpes Simplex Virus

Toxoplasmosis

Caused by protozoan Toxoplasma gondiiDomestic 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

Toxoplasma Infection

Acquired infection

immunocompetent individuals:

Asymptomatic or very mild infection

immunocompromised individuals:

high risk of fatal disseminated infection;

often reactivation

Congenital infection (in pregnancy):

- high risk of fetal damage or death after

- primary infection during pregnancy

Risk Factors for Congenital Toxoplasmosis

Primary Toxoplasma infection during pregnancy:

no known risk for congenital infection of infants born to immune women

no known risk of congenital infection in case of primary infection before conception

Time point of infection during pregnancy

Clinical Manifestations

Most (70-90%) are asymptomatic at birthClassic triad of symptoms:ChorioretinitisHydrocephalusIntracranial calcificationsOther symptoms include fever, rash, HSM, microcephaly, seizures, jaundice, thrombocytopenia, lymphadenopathy, premature-birth, still-birth/IUFDInitially asymptomatic infants are still at high risk of developing abnormalities, especially chorioretinitis

Chorioretinitis of congenital toxo

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 standardized

Toxo Screening

Prenatal testing with varied sensitivity not useful for screeningNeonatal screening with IgM testing implemented in some areasIdentifies infected asymptomatic infants who may benefit from therapy

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 pyrimethamine

Syphilis

T.Pallidum

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

Congenital Syphilis

2/3 of affected live-born infants are asymptomatic at birthClinical symptoms split into early or late (2 years is cut off)3 major classifications:Fetal effectsEarly effectsLate effects

Clinical Manifestations

Fetal:StillbirthNeonatal deathHydrops fetalisIntrauterine death in 25%Perinatal mortality in 25-30% if untreated

Clinical Manifestations

Early congenital (typically 1st 5 weeks):Cutaneous lesions (palms/soles)HSMJaundiceAnemiaSnufflesPeriostitis and metaphysial dystrophyFunisitis (umbilical cord vasculitis)

Periostitis of long bones seen in neonatal syphilis

Clinical Manifestations

Late congenital:Frontal bossingShort maxillaHigh palatal archHutchinson teeth8th nerve deafnessSaddle nose Perioral fissuresCan be prevented with appropriate treatment

Hutchinson teeth late result of congenital syphilis

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!!

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

Treatment

Penicillin 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

Rubella

Togavirus: single-stranded RNA virusIncubation - 14-21 daysRespiratory droplet inoculationonly modestly contagiousFever, rash (3 days), cough, arthralgias, post auricular and suboccipital lymphadenopathyUsually mild, overt clinical symptoms 50-75% of casesEncephalitis, bleeding diathesis & arthritis are rare complicationsInfection earlier in pregnancy has a higher probability of affected infant

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

Rubella and the Fetus

Blueberry muffin spots representing

extramedullary hematopoesis

Purpura, Splenomegaly, jaundice, meningoencephalitis, thrombocytopenia are transientCongenital cataracts, Glaucoma, heart disease, deafness, microcephaly and mental retardation are permanent abnormalitiesSequele: Diabetes, thyroid abnormalities, precocious puberty & progressive panencephalitis

Diagnosis

Maternal 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

Prevention and Treatment

Vaccination (95% seroconversion)

@ 15 months and early adulthood

Immune status checking in teenagers, pre-college and pre-pregnancy Antenatal testingSerology testing for presumed exposures (paired Sera)No in-utero therapy

Cytomegalovirus

DNA virusCongenital infection - 1%5-10% of those infected show clinical illness at birthNeonatal MR - 20-30%90% of survivors get late complications5-15% with no demonstrable disease at birth get some abnormality (deafness)

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

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

CMV Congenital Infection

Hepatomegaly}Spleenomegaly}Jaundice}TORCHThrombocytopenia}SyndromePetechiae}Microcephaly}Intrauterine growth retardation}

CMV Congenital Infection (Late)

VenticulomegalyCerebral atrophyMental retardationPsychomotor delaySeizuresLearning difficulties and language delayChorioretinitis / Optic atrophyIntracranial calcificationsLong bone radiolucencies, dental abnormalitiesPneumonitis

Ventriculomegaly and calcifications of congenital CMV

Diagnosis

Maternal IgG shows only past infectionInfection 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

Treatment

Ganciclovir 6wks in symptomatic infantsStudies 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 asymptomatic patients, etc.No vaccination

Herpes Simplex (HSV)

HSV1 or HSV2Primarily transmitted through infected maternal genital tractRationale for C-section delivery prior to membrane rupturePrimary infection with greater transmission risk than reactivation

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

Presentations of congenital HSV

Diagnosis

Culture of maternal lesions if present at deliveryCultures in infant:Skin lesions, oro/nasopharynx, eyes, urine, blood, rectum/stool, CSFCSF PCRSerologies again not helpful given high prevalence of HSV antibodies in population

*

Treatment

High dose acyclovir 60mg/kg/day divided q8hrsX21days for disseminated, CNS diseaseX14days for SEMOcular involvement requires topical therapy as well

Index of Suspicion

When do you think of TORCH infections?IUGR infantsHSMThrombocytopeniaUnusual rashConcerning maternal historyClassic findings of any specific infection

Conclusion

The main issues include

General principlesInfection and the fetal affectsSpecific problems for the fetus with maternal infections.Congenital syndromes - main features

Which TORCH Infections Can Absolutely Be Prevented?

RubellaSyphilis