1. Infections in Pregnancy CARIS – Public Health Wales 24.11.16
Dr Surabhi Nanda
Consultant Maternal Fetal Medicine
Honorary Senior Lecturer in Obstetrics

2. Case 1 a.30 G1P0 Low risk aneuploidy screen
20w anatomy scan-Echogenic bowel, growth and liquor normal.
Parental blood for - negative
Amnio for karyotype – declined
Rescan – Persistent echogenic bowel
TORCH screen
Positive IgM and IgG for CMV
CMV IgM positive :
Through polyclonal stimulation of Rheumatoid factor of IgM class
Persistence from a remote infection
Reactivation of a previous infection
Primary or preconceptional infection with CMV
1. Check booking blood Check avidity Amniocentesis

3. Interpretation basics
IgM
IgG
No Exposure -
Acute Infection +
+/-
Past infection

4. IgG avidity
“Functional affinity” - the net antigen binding force of the populations of antibodies,
in response to an infection.
The anti-CMV IgG avidity test is currently the most reliable procedure to identify primary infection in pregnant women- highly specific (100%) and sensitive (94.3%).
IgG avidity testing less invasive than amniotic fluid testing
IgG avidity index - low (0.57)
Low avidity IgG persists for 17w
Full maturation of antibody at 25w
Amniocentesis

5. Amniotic fluid CMV count = 4 million
Detection in amniotic fluid does not
necessarily correlate with congenital
infection
Amniotic fluid CMV count = 4 million
Booking bloods = CMV IgM & IgG positive (cf:primary infection occurred >6w previously)
Fetal blood sample - positive for virus
If fetal blood still carrying virus >6 weeks after primary infection then the risk to the fetus is high
Counselling:
Prevalence of CMV infection is around 0.5–1% of all live births
Leading infectious cause of sensorineural hearing loss (SNHL) and developmental delay (DD)
70% chance of DD
Vertical transmission in ~ 30–40% following primary infection and 2–3% following secondary infection
~only 5–10% of infected newborns will have symptoms at birth, 40-58% of whom develop adverse outcomes, including cerebral palsy, SNHL and other neurological problems.
around 90% of congenitally infected infants are asymptomatic, although 5–15% of them will develop SNHL
Limited evidence about risk of transmission at different periods of gestation

6. Opted to continue pregnancy.
3 weekly scans - 33 weeks intra cranial anatomy normal. Declined further FU Elective CS 39w Maternal Request
Early neonatal findings- mild ventriculomegaly on CT, and unilateral deafness
Infant development- motor delay at 6 months, bilateral deafness.
Audiology - The National Deaf Children's Society guidelines ( recommend hearing assessment for babies with cCMV should be performed every 3–6 months in the first year until age 3 and then yearly until 6 years old.
Neurodevelopmental - Clinical and neurodevelopmental follow up should be performed at 6 months and at least one year in general paediatric clinics. All CNS symptomatic infants should have a neurodevelopmental assessment at one year. Further referral to long term neurodevelopmental services will then be based on clinical need and neuroimaging findings.
Ophthalmology - Initial ophthalmology assessment is required at diagnosis. Symptomatic newborns should undergo annual ophthalmology assessment until the age of 5 to detect the presence of delayed or progressive chorioretinitis.
Family support - In the U.K the congenital CMV association ( is run on a voluntary basis by the parents of children with cCMV.
Currently antiviral treatment with GCV and
valganciclovir is only recommended for symptomatic
newborns (in the first 30 days of life) with severe symptomatic focal organ disease, or CNS disease.

7. Case 2 20 week anomaly scan 22 weeks - ascites a35, Para 1
Maternal APKD
Previous PIH
Low risk
Rhesus +
TORCH – CMV IgG- ; IgM+; Low Avidity
Booking Bloods – CMV IgG-; IgM-
Amniotic fluid CMV PCR 2.2x107
Acute Primary fetal CMV infection
Options – TOP Vs Expectant management
Opted for expectant
For review in 4 weeks and fetal MRI around weeks

8. Symmetrical prominent horns of the lateral ventricles
Symmetrical prominent horns of the lateral ventricles. Otherwise normal intracranial appearances.
Ascites resolved by 26 weeks
IOL 38 weeks
Admitted to NICU with tachypnoea, pallor, petechial rash and hepatomegaly.  Ventilated
CRANIAL USS – NO VENTRICULOEMGALY
CMV results: High concentrations in blood, lungs, urine and CSF
Platelets 35, Abnormal clotting.
1) Started valganciclovir
2) Audiology & Neurodevelopmental FU

10. Toxoplasma gondii 14% 29% 59% 41% 8% ~0%
Usually self limiting maternal infection which does not need treatment unless pregnancy or immunocompromised.
14%
29%
59%
41% 8%
~0% T1 T2 T3
Vertical transmission rate
Fetal severe sequele / Still birth

11. Toxoplasma infection in HIV positive women
High incidence congenital toxoplasmosis (CT)
Late manifestations of latent CT
Common with CD4<500 or women on HAART
Ocular and CNS manifestations more common
All HIV+ women with or without HAART need toxoplasma test +/- treatment in pregnancy

12. Diagnosis of acute infection
High titers of toxoplasmosis-specific IgM or IgA>95%
Toxoplasmosis-specific IgG and IgM rise in 1-2 weeks.
Toxoplasmosis-specific IgG peaks at about 2 months after infection.
Toxoplasmosis-specific IgA peak 4 weeks last about 7 months
USS findings associated with congenital toxoplasmosis
Ventriculomegaly
Calcifications
Intracerebral
Periventricular
Retinal
Lenticulostriate
Myocardial
Hepatic
Cataracts
Microphthalmia
Microcephaly
Non-immune hydrops
Ascites
Pleural effusion
Pericardial effusion
Hepatosplenomegaly
Placentomegaly

13. Case 3 a.30 Non English speaking traveller HIV –ve
Toxo serology +ve of acute infection
Amniocentesis – High Toxo PCR
Diagnosis – Congenital Toxoplasmosis
Counselling – Risks and Sequale
Options – Treatment vs (Termination)
Commence
Pyrimethamine mg/d, then mg/d
Sulfadiazine 1 gram QDS
Folinic Acid 5mg/d

14. Case 4 a.30 G1P0 Rh –ve Admitted with vaginal bleeding at 19 weeks
Placenta low posterior
Incidental finding of fetal hydrops
Fetal anaemia – MCA Peak systolic velocity >1.5MoM
Intrauterine fetal blood transfusion

15. 1st transfusion 19w - Hb 2.3g/dL (14.6 / 25mls)
Normal PCR and karyotype
Fetal blood +ve Parvo DNA (PCR3.8X 10Log=9.6)
Mum seroconverted after booking to positive Parvo IgG and IgM
Negative Toxo and CMV
1st transfusion 19w - Hb 2.3g/dL (14.6 / 25mls)
2nd transfusion 21w – Hb 5.3g/dL (14.4 /27mls)
Counselling
Cause for fetal anemia and hydrops is maternal Parvovirus B19 infection. This causes bone marrow suppression and is reversible. Until baby's bone marrow starts working again, we will have to support by giving adult
blood.

16. Parvovirus B19

17. Fetal implications more serious when maternal infection occurs during the first two trimesters of pregnancy
Spontaneous Miscarriage
<20w 14.8%
>20w 2.3%
2. Congenital anomalies
(No)association between
parvovirus infection in pregnancy and increased
risk of congenital anomalies in human fetus
(Case reports of some anomalies)
3. Hydrops
Non immune fetal hydrops secondary to anaemia
Myocarditis

18. Management of a pregnant woman with suspected or diagnosed Parvovirus

19. Acknowledgements
Prof Z Alfirevic
Dr D Roberts
Mr U Agarwal
Ms Jackie Holian
Fetal Medicine Unit
LWHNHSFT
Thank you