Perinatal infections

Question 1

Well in pregnancy. Infant thrombocytopenia, HSM, Periventricular intracranial calcifications, microcephaly, sensorineural hearing loss. Retinopathy.

Answer 1

CMV
- worst in first 6 months of pregnancy

Question 2

Diffuse intracranial calcifications, hydrocephalus, chorioretinitis, convulsions. Otherwise unexplained mononuclear CSF pleocytosis or elevated CSF protein. Intellectual disability.

Answer 2

Toxoplasmosis
- throughout pregnancy
b. Risk assessment = highest risk of infection 3rd trimester, highest risk of fetal damage 1st trimester
i. First trimester
1. Fetal infection = low risk 4-15% but if infected = high risk (34-85%) likely to be severe fetal damage
ii. Second trimester
1. Fetal infection = intermediate risk 25-44%
2. If infected = intermediate risk (18-33%) likely to be less severe
iii. Third trimester
1. Fetal infection = high risk 30-75%
2. If infected = low risk (4-17%), usually asymptomatic at birth

Question 3

• Skeletal abnormalities (osteochondritis and periostitis), deformed nails, abnormal epiphyses
• Pseudoparalysis
• Persistent rhinitis
• Maculopapular rash (particularly on palms and soles or in diaper area)
• Hepatosplenomegaly
• Congenital neurosyphilis
• Chorioretinitis

Answer 3

Syphilis
- throughout pregnancy

Question 4

• Cataracts, congenital glaucoma, pigmentary retinopathy
• Congenital heart disease (most commonly PDA or peripheral pulmonary artery stenosis)
• Radiolucent bone disease
• Sensorineural hearing loss
• Microcephaly

Answer 4

Rubella
- Up to 16 weeks although more significant in the first two months of pregnancy

Question 5

• Mucocutaneous vesicles
• CSF pleocytosis
• Thrombocytopenia
• Elevated liver transaminases
• Conjunctivitis or keratoconjuctivitis

Answer 5

HSV (perinatally acquired)
- CS reduces risk of transmission

Question 6

• Skin vesicles, ulcerations, or scarring
• Eye abnormalities (eg, micro-ophthalmia, chorioretinitis)
• Brain abnormalities (eg, hydranencephaly, microcephaly)
• Placental infarcts and inflammation of umbilical cord

Hydrops fetalis, Fetal in utero demise

Answer 6

HSV (in utero) - rare

Question 7

• Cicatricial (zigzag dermatomal) or vesicular skin lesions
• Microcephaly
• Skin and muscle defects
• Intrauterine growth retardation
• Limb reduction defects (hypoplasia)
• Neurological – microcephaly, cortical atrophy, seizures, DD
• Eye – chorioretinitis, microphthalmia, cataracts
• Renal – hydroureter/nephrosis
• ANS – neurogenic bladder, swallowing dysfunction, aspiration

Answer 7

Varicella
- first trimester

Question 8

• Microcephaly - severe, partial collapse of skill
• Intracranial calcifications - thin cerebral cortices
• Arthrogryposis
• Hypertonia/spasticity
• Ocular abnormalities - Macular scarring and focal pigmentary retinal mottling
• Sensorineural hearing loss

Answer 8

Zika
- up to 20 weeks gestation

Question 9

• Stillbirth
• Hydrops
• hydrocephaly

Answer 9

Parvovirus infection, B19
- up to 20 wks gestation

Question 10

Maternal primary infection of CMV - risk of transmission, symptomatic v asymptomatic congenital, risk of sequelae and normal

Answer 10

30% risk of transmission
i. Symptomatic congenital CMV = 10-15%
1. Risk of sequelae 50%
2. Normal 50%

ii. Asymptomatic congenital CMV = 85-90%
1. Risk of sequelae 10-15%
2. Normal 85-90%

Question 11

Maternal secondary infection of CMV - risk of transmission, symptomatic v asymptomatic congenital, risk of sequelae and normal

Answer 11

1% risk of transmission
i. Symptomatic congenital CMV <1%
ii. Asymptomatic congenital CMV >99%
iii. Risk of sequelae <10%

Question 12

Neonatal CMV management/follow up

Answer 12

Asymptomatic - No specific treatment, audiology f/up

Symptomatic = ganciclovir (IV), valganciclovir (PO)
6 months. If unwell – first 2 weeks IV ganciclovir, then change to oral
Monitoring for toxicity - FBE (neutropenia, thrombocytopaenia), LFT (hepatitis), UEC (nephrotoxicity)
Assessing treatment response
1. Clinical evaluation
2. Viraemia levels – goal non-detectable levels
iv. Antiviral resistance should be suspected in infants with progressive end-organ disease despite adequate treatment, rising levels over the first two weeks, or a sustained increase after an initial decline
v. Alternative if resistance – foscarnet

Question 13

HBV in pregnancy - risk of transmission

Answer 13

b. Overall risk of transmission 90% - reduced by 95% with management
c. Risk of transmission on maternal status
i. sAg +ve = carrier (5-20% vertical transmission)
ii. eAg +ve = higher risk carrier (90% transmission)

Question 14

HBV - neonatal

Answer 14

b. Neonate
i. All neonates = Hepatitis B vaccine + Ig (within 12 hours) - prevents 95% (even if mother eAg +ve)
ii. Usual vaccines at 2, 4 and 6 months
iii. Serology at 9-12 months including HBsAg and anti-HBs
c. NOTE
i. No evidence that offering LUSCS reduces risk
ii. Breastfeeding is recommended
iii. Consider minimising invasive procedures antenatally and intrapartum particularly in women with high viral lode

Question 15

HBC - neonatal

Answer 15

Maternal management
- Can’t treat during pregnancy, no effective interventions to reduce transmission
- Consider minimising invasive procedures
- No clear evidence that maternal LUSCS reduces transmission
- No increased risk with breastfeeding – however consider expressing and discarding milk if nipples cracked and bleeding
Neonate management
- HCV RNA test at 3/12
- HCV Ab test at 12-18 months – most uninfected infants are antibody negative by 12 months (maternal Ab until this time therefore cannot infer neonate infection) –> if positive do RNA and LFTs

Question 16

Maternal Mx of HSV

Answer 16

suppressive antiviral therapy from 36 weeks
c section if active lesions when in labour if possible

Question 17

Neonatal Mx HSV - low risk

Answer 17

i. Low risk
1. Mother with recurrent genital infection, OR
2. Mother with primary infection seroconverted well prior to delivery, AND
3. Without genital lesions at delivery
Practice varies between centres

Question 18

Neonatal Mx HSV - high risk

Answer 18

ii. High risk
1. Mother with primary genital infection close to delivery, OR
2. Infant born through birth canal with active HSV disease to mother with no prior history of active genital HSV
- Investigations
1. LP
2. FBE – thrombocytopaenia
3. LFTs
4. HSV PCR on blood
5. Surface swabs – eye, throat, umbilicus, rectum, urine
- Treatment = aciclovir

Question 19

Neonatal HSV timing

Answer 19

Skin/eyes/mouth: 10-12 days, up to 6 weeks; Rx aciclovir 2 weeks
CNS: 16-19 days, up to 6 weeks; 50% mortality Rx 3 weeks
Disseminated: 10-12 days; 80% mortality Rx 3 weeks

Question 20

RF for HIV vertical transmission

Answer 20

a. Majority of in utero transmission likely occur late in gestation – vascular integrity of the placenta weakens and microtransfusions across the maternal-fetal circulation occur
b. Maternal
i. High viral load
ii. Low CD4 count
iii. Non-compliance/incomplete treatment
c. Delivery
i. Preterm delivery (<34 weeks)
ii. ROM >4hours (doubles risk)
iii. Vaginal vs. C/S (CS decreased risk by 87% with zidovudine)
iv. Preterm <34/40
d. Baby
i. BW <2.5kg (doubles risk)

a. Intrauterine (before delivery) = PCR +ve at <48 hours of age
i. 20-30% of infected newborns are infected in utero (PCR positive in first week of life)
b. Intrapartum (during delivery) = PCR +ve at >48 hours of age

Question 21

Maternal Mx of HIV

Answer 21

i. Effective HAART important
ii. Vial load <50 copies/ml at 36 weeks gestation
1. If yes
a. No intrapartum zidovudine
b. Vaginal delivery if no obstetric contraindications
2. If no
a. Intrapartum zidovudine
b. Planned LUSCS

Question 22

Neonatal Mx of HIV

Answer 22

i. Avoid use of scalp clips in labour
ii. Infant ALWAYS fed with formula in developed countries (BF in developing countries)
iii. Commence antiretroviral prophylaxis (4/52) – varies based on the risk to the neonate
1. Low risk (<2%)
a. Zidovudine monotherapy within 6-12 hours for 4 weeks
2. High risk (>2%)
a. Lamivudine + neviarpine + zidovudine
b. PJP prophylaxis
iv. Testing infant
1. HIV PCR (DNA or RNA)
2. HIV antibody (only >=18 months of age)
3. Occur at least 2 weeks and 2 months after antiretroviral prophylaxis is ceased

Question 23

Maternal Mx TB in pregnancy

Answer 23

Treat! All drugs cross the placenta.
i. Isoniazid, rifampicin + ethambutol – safe during pregnancy
1. Isoniazid has a higher risk of hepatotoxicity – require close monitoring
ii. Pyrazinamide – less data; recommended by WHO
iii. Streptomycin is contraindicated in pregnancy

Question 24

Neonatal TB - absent but risk

Answer 24

Isoniazid for 6 months

Question 25

Contangiousity of parvovirus

Answer 25

B19 viraemia begins 6 days after exposure and lasts for one week – contagious prior to symptoms (5-10 days)
Risk of transmission to neonate = 50%
if <20 weeks - 10% foetal loss
9-20 wks - 3% hydrops: 1/3 resolve within 8 wks, 1/3 die without transfusion, 1/3 survive with transfusion

Question 26

Rubella primary infection risks

Answer 26

ii. 1-12 weeks = 80% infection, 85% congenital defects
iii. 13-16 weeks = 50% infection, 35% congenital defects
iv. 17-22 weeks = 36% infection, congenital defects rare
v. 23-30 weeks = 30% infection, congenital defects rare
vi. 31-36 weeks = 60% infection, congenital defects rare
vii. >36 weeks = 100% infection, congenital defects rare

Question 27

Toxoplasmosis neonatal Rx

Answer 27

Treatment = Pyrimethamine + sulphadoxine +/- spiramycin for one year
ii. Investigations
Infant blood IgM and/or IgA, IgG
Placental histology/PCR
Blood +/- CSF PCR
- Full clinical examination
- Imaging
- Ophthal review
- Audiology
2. If abnormal = symptomatic congenital toxoplasmosis
3. If normal = asymptomatic congenital toxoplasmosis [MAJORITY]

Long-term outcome
i. Chorioretinitis
ii. Developmental delay
iii. Seizures
iv. Microcephaly
v. Deafness

Question 28

Neonatal varicella risk

Answer 28

Neonatal Varicella

1. Transmission
   a. Neonatal varicella has high mortality – up to 30%
   i. WORST situation is VZV spreading via placental route
   b. Incubation period 14 days (max 21 days)
   c. IgG (from mum) takes 5 days to be produced and transmitted to babies
   d. Therefore, most risk of varicella occurs if:
   i. Mother has rash 5 days before birth (not time for IgG to cross), or
   ii. Mother develops rash 2 days after birth (because of 48 hours infectivity prior to appearance of rash)
   e. NOTE: exception is the premature neonate because no IgG crosses
2. Management of maternal chickenpox
   a. Dependent on timing of maternal chickenpox – in all cases breastfeeding encouraged and NO isolation
   b. Maternal chickenpox > 7 days before delivery  no intervention
   c. Maternal chickenpox 7 days before to 2 days after delivery  ZIG
   d. Maternal chickenpox >2-28 days after delivery  dependent on neonatal risk factors
   i. If infant <28 weeks gestation or <1000g birth weight give ZIG within 96 hours but can be given up to 10 days post maternal rash
   ii. Discharge term infants as soon as possible
   iii. Some experts give ZIG to term babies >2-28 days of age when mother develops chickenpox but little data to support this
   e. Newborn develops chickenpox
   i. Very-pre term infant in nursery  IV aciclovir
   ii. Term infant at home or on post-natal ward
3. Mild disease and ZIG given <24 hours after birth = observe, treat with IV aciclovir if respiratory symptoms
4. Severe disease or ZIG given >24 hours after birth = treat with IV aciclovir
5. Term neonate exposed to chickenpox
   a. Mother vaccinated  no further intervention
   b. Unsure or no maternal vaccine
   i. Positive serology  no further intervention
   ii. Seronegative or serology unavailable  consider ZIG to infant (ideally within 96 hours but can be given up to 10 days later)

Question 29

Neonatal varicella risk

Answer 29

Incubation period 14 days (max 21 days)
IgG (from mum) takes 5 days to be produced and transmitted to babies
Therefore, most risk of varicella occurs if:
- Mother has rash 5 days before birth (not time for IgG to cross), or
- Mother develops rash 2 days after birth (because of 48 hours infectivity prior to appearance of rash)
NOTE: exception is the premature neonate because no IgG crosses
2. Management of maternal chickenpox
- Dependent on timing of maternal chickenpox – in all cases breastfeeding encouraged and NO isolation
> 7 days before delivery  no intervention
7 days before to 2 days after delivery  ZIG
>2-28 days after delivery  dependent on neonatal risk factors
i. If infant <28 weeks gestation or <1000g birth weight give ZIG within 96 hours but can be given up to 10 days post maternal rash
iii. Some experts give ZIG to term babies >2-28 days of age when mother develops chickenpox but little data to support this
e. Newborn develops chickenpox
- Very-pre term infant in nursery  IV aciclovir
- Term infant at home or on post-natal ward
1. Mild disease and ZIG given <24 hours after birth = observe, treat with IV aciclovir if respiratory symptoms
2. Severe disease or ZIG given >24 hours after birth = treat with IV aciclovir
Term neonate exposed to chickenpox
- Mother vaccinated  no further intervention
- Unsure or no maternal vaccine
> Positive serology  no further intervention
> Seronegative or serology unavailable  consider ZIG to infant (ideally within 96 hours but can be given up to 10 days later)

Question 30

Conjunctivitis GN coccobacillus

Answer 30

chlamydia, usually 5-15day.
Involves tarsal conjunctiva
Oral erythromycin for 2 weeks + Treat the parents
5-30% get delayed onset pneumonia at 2-4 weeks – staccato cough

Question 31

Conjunctivitis GN diplococcus

Answer 31

gonorrhoea, within 5 days
Involves cornea
Hyper-purulent discharge, TRUE OCULAR EMERGENCY
Complications - Corneal ulceration, perforation, anterior synechiae, pan-ophthalmitis
Treatment: IV ceftriaxone, eye irrigation