1. Perinatal CMV Infection Kadri Matt Karin Asser Tartu University Women`s Clinic Tallinn 2006

2. Non - Human CMV Non - Human CMV

3. What about CMV Infection in Humans?  The knowledge about the virus and its pathogenity has increased  A majority of CMV infections are asymptomatic  Some symptomatic cases have tremendous clinical importance Combination of lesions: HSV and CMV

4. Descriription of a Case  The patient was 20 years of age, unmarried  During the first trimester of pregnancy she was treated for - Chlamydiosis - Chlamydiosis urogenitalis urogenitalis - Anaemia gravidarum - Anaemia gravidarum

5. Description of a Case Description of a Case  The patient was referred to Tartu University Women`s Hospital for a second opinion ultrasound because of suspected fetal hydrocephaly  At the gestational age of 18 weeks and 6 days the fetal cerebral lateral ventricles were within a normal range, 9 mm  The patient was asked to come back in 2 weeks

6.  The next ultrasound at our hospital was performed at 24 weeks and 2 days: it showed bilateral fetal cerebral ventriculomegaly (posterior horns 1.2 cm)  Cordocentesis revealed normal fetal karyotype 46xy  Maternal blood analysis showed fresh CMV infection (positive IgG and IgM antibodies)

7. Ultrasound at 30 weeks and 2 days  Estimated fetal weight (EFW) 1150 g (corresponding to 28 weeks)  Ventriculomegaly: posterior horns of fetal cerebral ventricles 1.4 cm, and periventricular hyperechogenic foci and periventricular hyperechogenic foci  Polyhydramnios: amniotic fluid index (AFI) 27  Normal blood flow in arteria umbilicalis

8. Fetal cerebral ventriculomegaly at 30 weeks 2 days

9. Ex consilio:  Graviditas in hebdomines 30+5 Infectio cytomegaloviralis congenita Infectio cytomegaloviralis congenita Hydrocephalus Hydrocephalus Polyhydramnion Polyhydramnion Retardatio incrementi foetalis intrauterina Retardatio incrementi foetalis intrauterina Decision: Decision: to terminate the pregnancy by induction in to terminate the pregnancy by induction in the 36th week of gestation or earlier in the the 36th week of gestation or earlier in the case of maternal/fetal indications. case of maternal/fetal indications.

10. Ultrasound at 36 weeks and 3 days  Intrauterine growth retardation: EFW 1830 g (corresponding to 32 weeks), EFW 1830 g (corresponding to 32 weeks), BPD 7.3 cm (29 weeks) BPD 7.3 cm (29 weeks)  Fetal cerebral lateral ventricles 1.7 cm  AFI 28  Reduced diastolic blood flow in arteria umbilicalis: PI 1.78

11. Delivery at 36 weeks and 5 days Delivery at 36 weeks and 5 days Stimulatio partus cum Oxytocini Stimulatio partus cum Oxytocini - male neonate 2000g/42cm - male neonate 2000g/42cm - Apgar score: 3 - 5 - 6 - Apgar score: 3 - 5 - 6 - cord blood: - cord blood: pH 7.13 pH 7.13 pCO 2 58.3 pCO 2 58.3 pO 2 16.2 pO 2 16.2 BE – 9.0 BE – 9.0 The neonate was intubated 5 minutes The neonate was intubated 5 minutes after birth and was taken into the neonatal after birth and was taken into the neonatal intensive care unit. intensive care unit.

12. In the NICU In the NICU  The newborn is pallid, with petechial rash and with multiple deformities, abnormal build, and arthrogryposis. Movements absent, consciousness disorder, insufficient hemodynamics.  Ultrasound: developed hydrocephaly  Blood at PCR: CMV positive

13. In the NICU  X-ray: arthro-sceletal athrogryposis

14. Ex consilio in the NICU Ex consilio in the NICU  Prognosis for neonate`s life is absent due to congenital multiorgan insufficiency.  The parents share the same opinion.  After 6 hours artificial ventilation is stopped – exitus letalis

15. Pathoanatomical diagnosis  Primary diseases: Infectio cytomegaloviralis congenita: meningoencephalitis, hepatitis, pancreatitis, nephritis et pneumonitis cytomegaloviralis et ex descriptionibus clinicis. Infectio cytomegaloviralis congenita: meningoencephalitis, hepatitis, pancreatitis, nephritis et pneumonitis cytomegaloviralis et ex descriptionibus clinicis.  Complications: Hydrocephalus et arthrogryposis totalis ex infectionis cytomegaloviralis. Retardatio incrementi foetalis intrauterina. Asphyxia perinatalis:hyperaemia venosa acuta organorum parenhymatosum et ex descriptionibus clinicic. Hydrocephalus et arthrogryposis totalis ex infectionis cytomegaloviralis. Retardatio incrementi foetalis intrauterina. Asphyxia perinatalis:hyperaemia venosa acuta organorum parenhymatosum et ex descriptionibus clinicic.

16. CMV infection  Is rarely of consequence to the pregnant woman herself  Intrauterine infection may result in devastating congenital disease

17. Congenital CMV infection The incidence of congenital CMV infection among live births The incidence of congenital CMV infection among live births 0.2 – 2.0% 0.2 – 2.0% 6-20% of neonates with congenital CMV infection are symptomatic 6-20% of neonates with congenital CMV infection are symptomatic at birth – cytomegalic inclusion disease develops at birth – cytomegalic inclusion disease develops In asymptomatic newborns In asymptomatic newborns it is the common cause of sensorineural hearing loss and mental retardation it is the common cause of sensorineural hearing loss and mental retardation

18. Congenital CMV – Cytomegalic Inclusion Disease Clinical findings are variable: Clinical findings are variable: hepatosplenomegaly hepatosplenomegaly jaundice jaundice thrombocytopenia with thrombocytopenia with purpura purpura chorioretinitis chorioretinitis cerebral calcifications cerebral calcifications microcephaly microcephaly hydrocephaly hydrocephaly

19. Cytomegaloviruses are Among the oldest known Among the oldest known viruses viruses Belong to the group of Belong to the group of herpes viruses herpes viruses Incl. DNA viruses Incl. DNA viruses

20. The virus is Intranuclear and is assembled Intranuclear and is assembled in the nucleus of the host in the nucleus of the host Individuals can be infected by Individuals can be infected by more than one strain – recurrent infections may develop more than one strain – recurrent infections may develop This makes diagnosis and management difficult This makes diagnosis and management difficult

21. Risk factors, transmission The highest prevalence of antibodies is found among lower socioeconomic groups The highest prevalence of antibodies is found among lower socioeconomic groups Most frequently transmission occurs Most frequently transmission occurs by the ororespiratory route… by the ororespiratory route… Seroconversion in Estonia is 90% Seroconversion in Estonia is 90%

22. CMV in pregnancy Pregnancy per se does Pregnancy per se does not alter the incidence of not alter the incidence of primary disease primary disease The virus is transmitted in The virus is transmitted in the absence of specific the absence of specific T-immunity T-immunity CMV transmission is possible during pregnancy, delivery and lactation CMV transmission is possible during pregnancy, delivery and lactation possibly by placental route possibly by placental route

23. Transmission  Maternal CMV-specific IgG have a protective effect against fetal infection  Transmission depends on the pre- conceptional serological status of the mother Transmission rate is 1.2 % for seropositive Transmission rate is 1.2 % for seropositive and 12.9 % for seronegative women and 12.9 % for seronegative women

24. Prenatal counselling of the gravida with evidence of primary infection  Counselling of a gravida with primary CMV infection is difficult  Negative amniocentesis fluid analyses by viral culture and PCR confirm a reasonably high probability that the fetus is not infected  Vertical transmission is possible in later gestation

25. Diagnosis of Infection in Pregnant Women Serologic tests for CMV specific IgG and IgM antibody from Serologic tests for CMV specific IgG and IgM antibody from maternal or fetal sera using maternal or fetal sera using ELISA, ABBOT IM or IMMULITE ELISA, ABBOT IM or IMMULITE CMV – DNA tests by PCR (B- CMV-DNA) from, maternal/fetal blood, sera, amniotic fluid, CMV – DNA tests by PCR (B- CMV-DNA) from, maternal/fetal blood, sera, amniotic fluid, neonate`s urine neonate`s urine

26. Prenatal Diagnosis of Congenital CMV Infection  A reliable prenatal diagnosis of congenital CMV infection is based on PCR from amniocentesis samples  Best sensitivity and 100% specificity by PCR from amniotic fluid is after 21 gestational weeks  Mean interval between the diagnosis of maternal infection and antenatal procedure is 7 weeks  CMV- specific IgM antibody detection from cord blood samples has a sensitivity of 60%

27. Prenatal Diagnosis of Congenital CMV Infection  Ultrasound has limited sensitivity in detection of fetal infection  Pregnancies with evidence of vertical transmission and definite ultrasound findings indicating suspected fetal damage are at significant risk of abnormal sequelae

28. Summary Primary maternal infection is difficult to diagnose unless identified by seroconversion. Primary maternal infection is difficult to diagnose unless identified by seroconversion. Routine serologic screening for CMV infection during pregnancy cannot be recommended. Routine serologic screening for CMV infection during pregnancy cannot be recommended. The documentation of maternal disease during pregnancy or confirmed congenital fetal CMV infection may be an indication for therapeutic abortion/ termination of pregnancy. The documentation of maternal disease during pregnancy or confirmed congenital fetal CMV infection may be an indication for therapeutic abortion/ termination of pregnancy.

29. Thank You Thank You