Congenital Infections Flashcards
What is the incidence of primary VZV infection in pregnancy?
3:1000
RCOG GTG
What type of virus is VZV?
DNA virus
Herpes family
How is VZV transmitted?
Highly contagious
Respiratory rollers
Direct personal contact with vesicle fluid
Indirectly via fomites
How does the primary infection of VZV present?
Fever
Malaise
Pruritic rash that develops into crops of maculopapules, which become vesicular and crust over before healing
What is the incubation period of VZV?
1-3 weeks
When is VZV infectious?
48 hours before the onset of the rash
Until the vesicles crust over (usually within 5 days of appearing)
What type of vaccine is the VZV vaccine?
Live attenuated vaccine
How long should women be advised to avoid conceiving for, after having the VZV vaccine?
4 weeks
What are risk factors for serious morbidity from primary VZV infection in pregnancy?
Second half of pregnancy
Immunocompromise (including systemic steroids within the last 3 months)
Smoking
Chronic lung disease
If a woman has been exposed to VZV, what should be offered? (And when and how does it work?)
VZIG
Varicella zoster immunoglobulin
ASAP, but up to 10 days after exposure (or up to 96 hours *ASID)
A second dose may be required if a further exposure is reported and 3 weeks have elapsed since the last dose
Human immunoglobulin product from plasma donors
Prevents or attenuates chickenpox in non-immune individuals
May reduce the risk of development of FVS (Fetal Varicella Syndrome)
What are the manifestations of severe VZV infection in adulthood?
Pneumonia
Hepatitis
Encephalitis
Death (rare)
What should a pregnant women be offered if she develops a chickenpox rash, and presents within 24 hours of the onset of the rash?
Oral Aciclovir
Synthetic nucleoside analogue
Inhibits replication of VZV
RCT: reduces duration of fever and symptomatology when compared to placebo
Accumulating data: no risk of major fetal malformation
What should a pregnant woman be offered if she develops severe VZV infection?
IV Aciclovir
Synthetic nucleoside analogue
Inhibits replication of VZV
Accumulating data: no risk of major fetal malformation
Up to what gestation, is there a risk of developing FVS with VZV?
28/40
What are the benefits and disadvantages of amniocentesis in the context of VZV in pregnancy?
VZV PCR
High sensitivity but low specificity
Good negative predictive value but poor positive predictive value
What are the manifestations of Fetal Varicella Syndrome?
Skin scarring in dermatomal distribution
Eye defects: microphthalmia, chorioretinitis, cataracts
Limb hypoplasia
Neurological abnormalities: microcephaly, hydrocephalus, cortical atrophy, mental retardation, dysfunction of bowel and bladder sphincters
With VZV in pregnancy, where should regional analgesia be performed?
At a site free of cutaneous lesions
Which neonates should receive prophylaxis with VZIG +/- aciclovir
For babies born to mothers who have had chickenpox within the period 7 days before delivery and up to 7 days post-delivery (up to 2 days from ASID)
(RCOG)
AND
Maternal chicken pox >2-28 days after delivery if infant <28 weeks or <1000g BW
What is the leading cause of congenital infections?
What is its prevalence?
CMV
0.64 - 0.7%
What is the meaning of CMV specific IgG avidity? What information does it provide?
Low avidity: recent primary infection
Intermediate avidity: recent primary infection cannot be excluded (manage as primary infection)
High avidity: past infection
How does CMV normally present?
Asymptomatic
Viral illness associated with atypical lymphocytosis
What is the difficulty with interpreting CMV IgM?
CMV IgM can persist for months after primary infection, or reappear with reactivation or re-infection
CMV IgG Avidity may assist in timing of CMV infection
Of all women with positive CMV IgM, only 25% are eventually diagnosed with a primary infection
What are risk factors for maternal CMV acquisition?
Frequent, prolonged contact with young children (in particular, those shedding CMV)
Day care workers
Parents with child in day care
Immunocompromised
Blood transfusions
Sexual contact
What is the % risk of congenital CMV infection to a fetus if mother has secondary CMV infection?
1%
When would an amniocentesis for CMV be performed?
6 weeks or more after primary maternal infection but not < 21 weeks gestation
PCR and culture
> 21/40: 80-100% sensitivity
<20/40: 45% sensitivity
High specificity at all times
Sensitivity also increased by waiting for 6/52 after maternal infection
What are non-invasive tests that can be performed once primary maternal CMV infection has been confirmed?
Fetal USS
- sensitivity <30-, low specificity
Fetal MRI
Congenital CMV infection:
Does risk of congenital infection increase or decrease with gestational age?
Does the severity and sequelae of congenital infection increase or decrease with gestational age?
Risk of infection increases with gestational age.
1st trimester 36%
2nd trimester 40%
3rd trimester 65%
Severity and sequelae decrease with gestational age
What are the fetal USS features associated with symptomatic congenital CMV infection?
Neuro: microcephaly, hydrocephalus, intracranial calcification,
Hydrops: ascites, polyhydramnios, pleural or pericardial effusions,
Abdo: hepatomegaly, abdominal calcification, hyperechogenic bowel, pseudomeconium ileus
Oligohydramnios or polyhydramnios
IUGR
What is the overall risk of long term sequelae in a child infected with CMV congenitally?
10-20%
With maternal CMV infection, what is the risk of fetal transmission in a primary vs non-primary infection?
Primary = 30% Non-primary = 1%
With transmission of CMV across the trimesters, what are the patterns of fetal outcomes?
First half of pregnancy: severe adverse neurological outcome
Late in pregnancy: acute visceral disease: hepatitis, pneumonia, purpura, severe thrombocytopenia
What are the main concerns of a symptomatic congenital CMV infection?
- Early mortality rate (first 3 months) between 5-10%
- Neurological sequelae of microcephaly, seizures, chorioretinitis, developmental delay
- Sensorineural hearing loss
What are the main concerns of an asymptomatic congenital CMV infection?
- Sensorineural hearing loss
2. Chorioretinitis
Outline management of a woman confirmed to have CMV in pregnancy
Maternal tx: nil needed if immunocompetent.
Fetal tx:
- Amniocentesis for PCR and culture: not predictive of fetal damage. Sensitivity improved if waits >=6 weeks after maternal infection and if >20 weeks GA.
- Serial USS +/- fetal MRI
- Consideration of TOP if amnio PCR positive
- Traditionally, no tx for prevention of congenital infection but if CMV amnio PCR +ve, can given CMV immunoglobulin to improve infected baby outcomes.
- recent RCT published in the Lancet found that giving mum Valciclovir reduces fetal transmission of CMV, after maternal infection in early pregnancy
What tests should neonates affected by congenital CMV have at birth?
Serology: CMV IgM
CMV PCR: Urine, saliva, blood
If either serology or PCR positive, for Head USS, MRI, hearing and ophthalmic review
FBC, LFTs
Hearing screen at birth
Hearings assessment 6 monthly until age of 2 and then annually until age 6 due to possibility of delayed onset of sensorineural hearing loss
What should neonates affected by congenital CMV be treated with?
Valganciclovir
What are practices for pregnant women to reduce CMV infection?
- Assume that children under age 3 years have CMV in their urine and saliva
- Thoroughly wash hands with soap and warm water after diaphragmatic change, feeding or bathing a child, wiping child’s nose / drool, handling children’s toys, pacifiers, toothbrushes
- Do not share cults, plates, utensils, toothbrushes or food, towels or wash clothes with child
What postnatal advice would you give a mother of a CMV congenitally infected baby?
- Baby will be high CMV shedder for first years of life; use CMV hygiene precautions.
- Wait at least 6 months after primary CMV infection before trying to conceive
How does enterovirus present in adults?
90% asymptomatic or non-specific febrile illness
Sore throat, flu-like symptoms, vomiting. Diarrhoea less common.
Meningo-encephalitis far less common.
How does neonatal enterovirus present?
Wide spectrum: from non-specific febrile illness to fatal multisystem disease
Fever, irritability, poor feeding, lethargy
Maculopapular rash (50%)
Respiratory symptoms 50%
Gastrointestinal symptoms (20%)
Hepatitis (50%)
May have myocarditis, meningo-encephalitis
How is enterovirus transmitted?
In-utero transmission in late gestation has been described
Intrapartum exposure to maternal blood, genital secretions and stool
Postnatal exposure to oropharyngeal secretions from mother and other contacts
How is enterovirus diagnosed?
RT-PCR: rapid, sensitive and specific
Detection in blood, CSF, tissue most reliable
Genotype got possible by PCR sequencing of structural protein genes
- traditionally cell culture is slow and insensitive
- serology has very limited use
What is the treatment for neonatal enterovirus?
No antivirals currently available
IVIG may be of benefit - one small RCT showed subtle clinical benefits and faster resolution of viraemia
How can we prevent enterovirus?.
Hand washing / infection control contact precautions
Prophylactic IVIG may reduce disease severity in some exposed neonates
All HbsAg positive women require medical referral either during pregnancy or postpartum to…
- Assess the need for maternal treatment
- Hepatocellular carcinoma surveillance
- Reduce risk of vertical transmission
What is the treatment for a women who is HbsAg positive, with HBV DNA <10x7 IU/mL
HB IG and birth dose
HBV vaccine
Follow up of infant
What is the treatment for a women who is HbsAg positive, with HBV DNA >10x7 IU/mL
Treat mother with antiviral tenofovir from 30/40.
HBIG and birth dose HBV vaccine for infant (schedule at birth, 6 weeks, 3 months and 5 months)
Monitor for postpartum flare: check ALT every 4 weeks, for 2-3 months
The optimal time to stop therapy postpartum is not clear.
Stop 6 weeks postpartum.
If someone is HbsAg positive, what are the blood tests to organise?
HepB e antigen
HBV viral load
LFTs
What is the timeframe for HBIG and HBV vaccination in a newborn with an affected mother?
Ideally within 12 hours of delivery
Do not delay beyond 7 days of life
For a women with HBsAg positive, what is the neonatal management
HBIG and Hep B vaccine within 12 hours
Further HepB vaccine at 6 weeks, 3 and 5 months
Follow up serology at 9 months including HBsAg and anti-HBs.
- If HBsAg negative and anti-HBs <10IU /mL, consider further vaccine doses
- if HBsAg negative and anti-HBs >10IU/mL, no further action
- if HBsAg positive, refer for ongoing management by paeds gastro.
Note: LBW infants do not respond as well to Hep B courses so they require the normal vaccination as outlined above
PLUS
Measuring anti-Hbs at 7 months and if anti-HBs <10IU/mL, giving booster at 12 months
OR empirically giving a booster at 12 months
How do you a manage a pregnant woman who has potentially been exposed to Hep B?
Check anti-Hbs.
If >10IU/mL, suggests immunity.
Nil further action required. Hep B vaccine to the infant at birth, 2, 4, 6 months of age
If <10IU/mL, suggests non-immune
HepB Vaccine and HBIG within 72 hours of exposure
Vaccine to also be given at 1 and 6 months after first dose
Repeat testing of mother for HBsAg at 3 months
IgM other becomes HBsAg positive, further management required
What mode of delivery is recommended for a pregnant women with Hep B?
No specific advice
Insufficient evidence that offering a CS provides additional protection against perinatal Hep B transmission over the recommended neonatal regiment f Hep B IgG and vaccination.
What are the breastfeeding implications of maternal Hep B?
None. Breastfeeding is recommended
What are the considerations antenatally and in labour for a woman with Hep B?
Avoid invasive procedures antenatally: CVS, transplacental amniocentesis.
Use NIPT as alternative to IPT.
Avoid invasive procedures intrapartum (FSE, FBS, ventouse)
Particularly in women with high viral load, although the magnitude of benefit in preventing perinatal transmission is uncertain
What is the first thing to do when a pregnant woman has a HepC antibody positive result?
Confirm antibody test result unless known to be HCV positive
Hep C RNA and LFTs, HIV serology
If Hep C RNA positive, increased risk of vertical transmission of 5%; increased to 20% with HIV co-infection.
If Hep C RNA negative, may represent
- false positive antibody result
- past cleared infection
- past successful treatment
- low level viraemia below assay detection level
What are the considerations for a woman antenatally and in labour with Hep C?
Consider minimising invasive procedures antenatally and intrapartum, particularly in women with high viral load, although the magnitude of benefit in preventing perinatal transmission is uncertain
What is the recommendation regarding mode of delivery for a woman with Hep C?
CS only for obstetric indications.
No clear evidence that Caesarean section reduces perinatal HCV transmission
What is the recommendation regarding breastfeeding for a woman with Hep C?
No increased risk of transmission unless niples are cracked or bleeding.
Express and discard milk until cracked nipples healed.
What is the treatment for HepC in pregnancy?
Treatment during pregnancy is contraindicated
However, HepC RNA positive women should be referred to a gastroenterologist or ID physician for consideration of treatment postpartum
What is the neonatal management of maternal HepC?
Bath baby prior to any injections.
HCV RNA test at/after 3 months
- if negative, consider testing for HCV antibody (Ab) at /after 18 months to demonstrate passive maternal antibody clearance
OR can skip 3 months test and just do HCV antibody at 18 months.
- if HCV antibody negative: not infected
- if HCV antibody positive: check HCV RNA and LFTs, and if HCV RNA positive, refer to Paeds Gastro or ID
Infant considered infect with HCV if HCV RNA detected in two samples 3 months apart in first year OR HCV antibody positive after 18 months.
What is the antiviral treatment offered to women who are HCV prior to pregnancy?
Ribavirin.
Considered teratogenic so not recommended in pregnancy or breastfeeding.
Reliable contraception during and for 6 months after tx.
Sustained viral response (absence of viral DNA at 12-24 weeks) in >90%.
What is the risk of transmission of HCV via percutaneous needlestick injury?
1-3% only if from HCV RNA positive patients.
How do we test for HIV in pregnancy?
Pre-test counselling!
Screen with ELISA
Confirm with Western Blot
What is the management of an indeterminate Western blot result?
Further testing needed
Discuss with HIV reference lab and physician specialising in HIV