CMV In Pregnancy Leili Chamani. MD. MPH. Specialist In Infectious Diseases Department Of Reproductive Health Avesina Research Center (ARC)

* The most common vertically transmitted viral infection in the developed world is CMV. *Seropositivity rates in the adult population over 40 years of age world wide are 60%- 100%. (possibly due to transmission of virus through breastfeeding, sexual contact and spread from children.) *Seropositivity rates in pregnant women in Australia: 71% *primary infection occuring in 1.5% of these pregnancies. *Intrauterine infection occurs in: 50% of primary maternal CMV infections. *5-10% of infected babies are symptomatic.

Vertical Transmission:  pre-natally (transplacental, in utero acquisition) resulting in congenital CMV infection,  natally (infection acquired during labour and delivery),  or in the immediate post-natal period (usually transmitted via the breast milk of CMV- seropositive women).

The associated morbidity and sequelae of CMV vary depending on the:  route of acquisition of infection  timing of infection (esp: first 16 weeks of pregnancy)  and maternal immune status recurrent or non primary maternal infection during pregnancy carries a much lower risk to the fetus

CONGENITAL CMV INFECTION  occurs in 0.5–2.0% of all deliveries in the developed world. In the USA, this corresponds to approximately infants annually  5%-10% of these infants have clinical evidence of the disease at birth

Cytomegalic Inclusion Disease (CID) Of The Newborn  visceral organomegaly,  microcephaly with intracranial calcifications,  chorioretinitis  skin manifestations including petechiae and purpura.  and virtually all babies with this condition have profound neuro-developmental handicap, including mental retardation and sensorineural deafness.

PERINATAL CMV INFECTION May occur by one of three routes:  Exposure to CMV in the birth canal;  Transmission by blood transfusion;  Transmission by breast-feeding ( in premature infants can produce life- threatening disease)

Diagnosis  Maternal infection: *Serology : seroconvertion or a 4 fold increase in CMV-IgG Titer. IgM= Best maternal screening test (primary infection & recurrence) * Culture: Urine, Saliva, Cervicovaginal secretions.  Fetal infection: Isolation the virus from amniotic fluid Amniotic fluid PCR(Weeks 21-23) Cord blood CMV-IgM(neither sensitive,nor specific)

Diagnosis:  Women seroposirive for CMV befor conception: No more lab tests needed, unless particular clinical conditions  Pregnant women seronegative for CMV befor conception: Months 2-4 of gestation automated test for CMV-spesific IgG Positive result = seroconvertion = primary maternal infetion  Pregnant women with unknown pre- conception serological status for CMV: Months 2- 4 of gestation: automated test for CMV- specific IgG and IgM Positive IgM (<18 weeks= infected newborn.) Avidity for CMV-IgG Type of infection: a.Primary =low b.recurrent =high c.undefined Avidity:Reactivity to different CMV proteins

Findings in the fetus  Oligohydramnios or polyhydramnios  Non-immune hydrops  Fetal asctis  Intrauterine growth retardation  Microcephaly  Cerebral ventriculomegaly or hydrocephalus  Intracranial calcifications  Pleral or pericardial effusion  Hepatomegaly  Intrahepatic calcifications  Pseudomeconium ileus

Strategies for: Preventing Congenital CMV Infection A - Cytomegalovirus vaccines currently in clinical trial evaluation * Live, attenuated vaccines Towne Vaccine Towne–Toledo ‘chimera’ vaccines *Subunit vaccines Glycoprotein B (gB) protein subunit canarypox-gB (ALVAC) canarypox-pp65 (ALVAC)vaccines Additional data are needed B - Monitoring For CMV Infection Durig Pregnancy C -Strict hygene practices for seronegative women

Strategies for Management of Congenital CMV Infections  Antiviral Therapy For Prevention And Treatment Of Neonatal CMV Infections * Ganciclovir remains the gold standard, but concerns about its myelosuppressive effect and a lack of data about safety during pregnancy have limited its evaluation for perinatally acquired CMV infections. * Ganciclovir treatment of symptomatic CMV infection with CNS involvement in neonates was shown, in a controlledclinical trial, to improve hearing outcomes  Screening For Neonatal CMV Infections Virus isolation & culture long lasting CMV- Igm in child blood Additional data are needed