"Congenital Cytomegalovirus Infection, Update on Treatment"

1. Congenital Cytomegalovirus Infection
Update on Treatment
PREPARED BY
Basem Hamed
Lecturer of OB&Gyne - Zagazig university

2. EPIDEMIOLOGY

3. • Cytomegalovirus (CMV), is the most common viral cause of
congenital infection, affecting 0.2–2.2% of all live births.
• It is the leading non-genetic cause of sensorineural hearing loss
(SNHL) and a major cause of neurological disability.
• Around 10–15% of neonates with congenital CMV will be
symptomatic at birth.
BACKGROUND

4. • CMV infection may be
1. Primary…. acquired for the first time during pregnancy.
2. Secondary …… either by reactivation of prior CMV infection
or by a new infection with a different strain of the virus.
EPIDEMIOLOGY

5. Transmission of the virus to the fetus
1. Antenatally by the transplacental route.
2. During labour and delivery through contact with
cervicovaginal secretions and blood
3. Postnatally through breast milk.
EPIDEMIOLOGY

6. Golden Rules
• The risk of congenital infection appears to vary according to the
nature of infection.
Primary infection….. 30–40%
Recurrent infection…..1-2%
EPIDEMIOLOGY

7. Golden Rules
• The risk of congenital infection appears to vary according to the
time of 1ry infection.
 1st trimester…. 30%
 3rd trimester…. 47%
EPIDEMIOLOGY

8. Golden Rules
• While the risk of viral transmission is higher in third trimester,
the proportion of cases with severe fetal infection is higher in
the first trimester of pregnancy.
EPIDEMIOLOGY

9. Golden Rules
• Although CMV transmission is more likely in women with
primary infection, at the population level, especially in
populations with high CMV seroprevalence, the majority
(around two-thirds) of infants with congenital CMV infection are
born to women with pre-existing CMV immunity.
EPIDEMIOLOGY

10. CLINICAL PICTRE

11. Majority ….. asymptomatic.
Minority …. symptoms similar to those of IMN (glandular fever),
including fever, malaise, myalgia, cervical lymphadenopathy and,
less commonly, hepatitis and pneumonia.
NB;- CMV can remain dormant lifelong at particular sites, primarily in the
salivary glands, but the virus can be reactivated during pregnancy
PICTRE OF MOTHER

12. …… symptomatic at birth (jaundice, petechial rash,
hepatosplenomegaly, microcephaly and SGR).
…… asymptomatic (6–23% of these asymptomatic neonates
will later develop some degree of hearing loss).
PICTURE OF BABY
13%
87%

13. SCREENING FOR CONG.
CMV

14. routine prenatal screening is
NOT
recommended outside the research setting
SCREENING FOR CONG. CMV

15. Screening of CMV is offered only to pregnant women who
have.
1. influenza-like symptoms
2. glandular fever symptoms (with negative Epstein–Barr virus)
3. hepatitis symptoms(with negative test results for hepatitis A, B,
C)
4. routine ultrasound detects fetal abnormalities suggestive of
CMV infection
SCREENING FOR CONG. CMV

16. • ventriculomegaly
• microcephaly
• calcifications
• intraventricular synechiae
• intracranial haemorrhage
• periventricular cysts
• cerebellar hypoplasia
• cortical abnormalities
• echogenic bowel
• small for gestational age
• pericardial effusion, ascites
and fetal hydrops.
SCREENING FOR CONG. CMV
Ultrasound criteria of possible CMV infection

17. • IgM is not always diagnostic of recent primary CMV
infection for for several reasons:-
1. IgM may persist for many months after the primary CMV infection.
2. IgM may be detected during a secondary infection.
3. Cross-reactivity with IgM due to another viral infection, e.g. Epstein–Barr v.
4. IgM may be a result of nonspecific polyclonal stimulation of the immune sys.
SCREENING FOR CONG. CMV

18. IgG avidity testing is used to define the timing of the
infection (i.e. before or during pregnancy).
• What is Avidity test??
Avidity levels describes the proportion of IgG bound to the antigen.
• Results??
 High avidity index (>60%) …. past (more than 3 m) or secondary infection
 Low avidity index (<30%) …..recent primary infection (within the past 3 m).
SCREENING FOR CONG. CMV

19. The diagnosis of primary CMV infection in pregnancy can
be made by one of the following findings:
1. The appearance of CMV-specific IgG in a woman who was
previously seronegative.
2. The detection of CMV IgM antibody + low IgG avidity
SCREENING FOR CONG. CMV

20. Diagnosis of secondary CMV infection can be difficult.
• A rise in IgG levels does not confirm secondary infection as this may
be due to nonspecific polyclonal stimulation of the immune system.
• The only way of confirming secondary CMV infection (whether
reinfection or reactivation) is by invasive testing.
SCREENING FOR CONG. CMV

21. Fetal infection diagnosis:-
• The mainstay of diagnosis of fetal infection is by identification of
the viral DNA (PCR) in the amniotic fluid following amniocentesis.
• Timing??? the appearance of the virus in the amniotic fluid is
dependent on excretion of the virus in fetal urine. It should be
performed, therefore, after 20 weeks of gestation when fetal
urination is well-established.
SCREENING FOR CONG. CMV

22. PROGNOSTIC INDICATORS

23. 1- TIMING
….infection earlier in pregnancy is associated with
greater risk of fetal harm
PROGNOSTIC INDICATORS

24. 2- IMAGING
• Main sonographic prognostic indicator is fetal cerebral
abnormalities
• When both ultrasound and MRI of the fetal brain are normal
prenatally, the neonatal outcome is generally good (95% sensitivity
when both are performed in the third trimester)
PROGNOSTIC INDICATORS

25. 2- IMAGING
• When fetal CMV infection has been confirmed by amniocentesis,
serial ultrasound should be every 2–3 weeks e detailed assessment
of the fetal brain.
• MRI brain is complementary to US, indicated at 28–32 w (and
sometimes repeated 3–4 weeks later).
PROGNOSTIC INDICATORS

26. 3- FETAL VIRAL LOAD
• higher in symptomatic compared with asymptomatic neonates
PROGNOSTIC INDICATORS

27. 4- VIRAL& NON VIRAL FACTORS
• The best viral markers were fetal IgM and DNAemia.
• The best nonviral factors for differentiating symptomatic from
asymptomatic congenital infection were beta-2- microglobulin and
platelet count.
PROGNOSTIC INDICATORS

28. PRENATAL THERAPY

29. In immunocompromised (nonpregnant) women, the antiviral drugs
which are licensed for use for CMV infection include:-
Ganciclovir
Valganciclovir
Cidofovir
Foscarnet
Valaciclovir
1- ANTIVIRAL DRUGS

30. • With the exception of valaciclovir, their teratogenic and toxic effects
preclude their use in pregnancy.
• Valaciclovir is a prodrug that is converted in vivo by esterases into
the active drug acyclovir in the liver during first pass metabolism.
• Valaciclovir is favoured because it has greater oral bioavailability
than aciclovir (55% versus 10–20%).
1- ANTIVIRAL DRUGS

31. • Two studies were conducted giving conflicting findings.
• HIG is not routinely recommended for the treatment of women with
primary CMV infection in pregnancy, and should be reserved for use
in the research setting.
• A trial assessing HIG in pregnancy is currently underway and is
estimated to conclude at the end of 2018
2- HYPERIMMUNE GLOBULIN
(HIG)

32. COUNSELLING FOR TOP

33. Infected fetuses may be classified into one of three
prognostic categories:
1. Asymptomatic fetuses.
2. Severely symptomatic fetuses.
3. Mild or moderately symptomatic fetuses
COUNSELLING FOR TOP

34. 1. Asymptomatic fetuses: those with
no ultrasound abnormalities
normal cerebral MRI
normal biological parameters (in particular fetal platelet count).
Prognosis….. good but with a residual risk of hearing loss.
COUNSELLING FOR TOP
Prognosis

35. 2. Severely symptomatic fetuses: those with
severe cerebral ultrasound abnormalities
associated with fetal thrombocytopenia.
Prognosis ….. poor and counselling regarding the option of
termination of pregnancy should take place.
COUNSELLING FOR TOP
Prognosis

36. 3- Mild or moderately symptomatic fetuses: those with
Isolated biological abnormalities (fetal blood sampling)
NO brain abnormalities
+/-isolated ultrasound abnormalities(hyperechogenic
bowel, mild ventriculomegaly, isolated calcifications).
COUNSELLING FOR TOP

38. uncertain and further follow-up (US & MRI) may help to
refine the prognosis.
 Therapeutic options, such as antiviral therapy, are
being evaluated but their use is still limited to the
research.
 The option of termination of pregnancy should also be
discussed.
COUNSELLING FOR TOP
Prognosis

39. PREVENTION & MANAGEMENT

40. • There is no licensed vaccine for CMV.
• Behaviour modification (handwashing after contact with urine or
saliva, and avoiding sharing utensils, drinks or food with young
children).
PREVENTION

41. • Congenital CMV should be confirmed at birth (e.g. urine or oral
swab for CMV PCR within 3 weeks of birth).
• In neonates with symptomatic congenital CMV infection, postnatal
valganciclovir/ganciclovir treatment should be considered and
commenced within the first 4 weeks of life.
MANAGEMENT

42. • There is evidence that treatment can reduce or prevent progression
of SNHL and improve long-term neurodevelopmental outcomes in
some infants.
MANAGEMENT

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