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

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 2. Check avidity 3. Amniocentesis

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

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

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

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 (http://www.ndcs.org.uk) 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 (www.cmvsupport.org) 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.

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 28-30 weeks

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

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

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

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

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 - 100 mg/d, then 25-50 mg/d Sulfadiazine 1 gram QDS Folinic Acid 5mg/d

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

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.

Parvovirus B19

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

Management of a pregnant woman with suspected or diagnosed Parvovirus

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