Perinatal infections- GBS, parvo, varicella, listeria, HIV

Question 1

Describe how a swab is taken and sent for culture of Group B Streptococcus (GBS) to provide the highest rate of detection of colonisation. (3 marks)

Answer 1

• Perform at 35-37/40 gestation
• Can be a self swab or by clinician. Speculum should not be used.
• Take swab out of packaging, do not touch cotton bud end
• Insert cotton bud end 2cm into vagina
• Insert same swab 1cm into anus
• Place in sterile medium tube of selective enrichment broth (if not then false negative of 50%), label, send with form requesting GBS culture with pt name, NHI, details and gestation.
• Should be processed as soon as possible.
- Specify that swab has been taken for GBS screening and if penicillin allergy lab should test for sensitivities

Question 2

Describe and evaluate two different strategies for the prevention of early onset neonatal GBS disease. (8 marks)
A: Name the 2 approaches

Answer 2

Universal screening vs risk based screening

Question 3

Evaluate universal screening

Answer 3

Universal Screening
- All women are screened with LVS/anogenital swab for GBS at 35-37 weeks gestation. (or 3-5/52 prior to delivery if high risk and being delivered earlier)
- If GBS positive on swab:
o IAP (intrapartum antibiotic prophylaxis) is given
o Recommend immediate IOL if SROM at term
- If GBS negative on swab:
o No IAP required
- Exceptions:
o No IAP required for elective C/S with intact membranes even if GBS positive (but swab should still be done in case of SROM prior to elective date)
o Women with previous affected baby with GBS sepsis or GBS bacturia in current pregnancy should not be swabbed as should receive IAP regardless as result

    Benefits:	

• Studies have shown decreased rates of early onset GBS sepsis in neonates, RR 0.46 (although decrease in mortality not shown) Australian study shown decrease by 84%, NNT 224
• Will pick up more women colonised with GBS
• Likely cost effective

Disadvantages:

• More expensive
• More labour intensive
• Medicalisation of pregnancy and labour
• Need for greater resources to facilitate immediate IOL for SROM at term
• Some women will be given antibiotics unecessarily
• Antibiotic allergies can occur
• Some women will be missed e.g. late bookers/unbooked women
• Doesnt prevent all cases of maternal/neonatal GBS infection

Question 4

Evaluate risk based screening

Answer 4

2. Risk Based Screenng
   - No routine swabs for GBS
   - Women should be given IAP if:
   o Previous GBS infected neonate
   o Previous GBS bacturia (any colony count) in this pregnancy
   o GBS on swabs done for another reason in the pregnancy (unless has had LV at 35-37 weeks which is negative)
   o Ruptured membranes >18hrs
   o Maternal fever >38 degrees or clinical chorioamnionitis
   o Preterm labour <37 weeks gestationAdvantages:

• Cheaper
• Fewer unnecessary antibiotics given
• Fewer cases of anaphylaxis/allergic reaction
• Can apply to any woman who presents in labour
• Although less effective, still low EOGBS rate

    Disadvantages:

• May miss some GBS postive women
• Less effective at protecting against EOGBS

Question 5

Discuss the antibiotics used for intrapartum chemoprophylaxis of early onset neonatal GBS disease. (4 marks)

Answer 5

IV antibiotics should be given in labour if GBS positive or risk factors for EOGBS infection.
Aim for at least 4 hours prior to delivery, so give when in active labour until delivery.

Suggested regime from ASID: (however other local guidelines may differ)
- 1st line – benzylpenicillin 3g IV loading dose then 1.8g IV q4 hourly (penicillin preferred over amoxicillin as narrower spectrum of cover)
- Penicillin hypersensitivity without history of anaphylaxis:
o Cefazolin 2g IV loading dose then 1g q8hrly
- Penicillin or cephalosporin allergy at risk of anaphylaxis:
o Clindamycin 600mg IV q8hrly (ask for sensitivities at time of sending swab if penicillin allergic as 20% clindamycin resistance of GBS), OR
o Vancomycin 1g IV q12hrly
o (Erythromycin no longer an acceptable alternative - resistance rates of 30%).

• If signs of maternal sepsis broaden antibiotic cover to:
  o Amoxycillin 2g IV q6hrly, PLUS
  o Gentamicin 4-6mg/kg IV daily, PLUS
  o Metronidazole 500mg IV q12hrly

If delivered by elective pre rupture of membranes C/S – not required.

Question 6

Leading cause of neonatal sepsis in developed countries?

Answer 6

GBS

Question 7

Incidence of GBS without abx prophylaxis?

Mortality rate?

Answer 7

0.4-4 per 1,000 live births

Mortality rate of 14%. 20% if preterm.

Question 8

Parvovirus - pregnancy complications and effects on fetus?

Answer 8

• In pregnancy it can cause miscarriage, still birth, fetal anaemia, hydrops.
• Rate of vertical transmission in an acute parvovirus infection is 50% and greatest risk to fetus is between 8 and 20/40.
• Inhibits fetal EPO synthesis – leading to anaemia, hydrops and death.
• Excess mortality 10% in affected fetuses.
• Of affected fetuses, around 3% will develop hydrops.
• Consequences of infection should be seen by 8/52 after infection.
• If no evidence of USS proven abnormality by 30/40 - can be managed as low risk pregnancy
• No evidence that the virus causes long term disability.

Question 9

Risk factors and how is parvovirus transmitted?

Answer 9

Rate of transmission: respiratory, via blood products, vertical.
Sx: non specific muscle aches and pain, febrile illness with rash, can also have diarrhoea/vomiting/headache/nausea. Can then develop rash on face and trunk.
Sx typicially last 1/52.
Women working at childcare are at an increased risk of exposure. Overall risk around 2-4%.

Question 10

How to diagnose Parvovirus?

Answer 10

Diagnosis with IgG and IgM testing. Can use PCR but usually reserved for amniocentesis or if convincing hx with negative IgM.

Question 11

Management if confirmed parvovirus infection?

Answer 11

1-2 weekly USS surveillance for hydrops and MCA PSV for fetal anaemia for 12 weeks from exposure or until 30/40.

If abnormal MCA PSV or hydrops - transfer to unit for cord blood sampling +/-IUT.

If evidence of hydrops delivery or intrauterine transfusion may be required.

In the event of delivery- at level 3 unit with NICU.

Question 12

What advice should be given to pregnant women to reduce their risk of getting listeria?

Answer 12

Obtained from eating contaminated food, listeria lives indust/sewage/water/plants/soil/animal dropping.

Recommend avoiding soft cheese, chilled meals, cold meats, pate, unpasteurised milk.

Recommend pregnant women adopt safe food handling practices e.g. washing hands/keeping uncooked meat separate from vegetables etc.

Question 13

Pregnancy risks of Listeria?

Answer 13

miscarriage,
stillbirth,
preterm labour,
neonatal infection (pneumonia, meningitis).
Suspect listeria in a preterm baby with mec liquor.

Question 14

i) Explain the characteristics of Listeria monocytogenes that account for this rare infection being 20 times more common in pregnant women than in the general population. (2 marks)

Answer 14

• Listeria is a facultative intracellular gram positive bacilli
• Cell-mediated infection is a primary host defence against listeria
• Reduced cell-mediated immunity in pregnancy leads to higher susceptibility.
• Listeria has a low virulence in general population

Question 15

Probability of mother to child transmission with HIV? How to prevent transmission?

Answer 15

The probability of mother to child transmission:
2% in low risk cases - where proper prophylaxis used (probably lower <1%)
20% MTCT in high risk cases
Additional 20% risk if breast feeding

Risk of transmission if breastfeeding on HAART = 5%

Interventions to reduce vertical transmission include:
• Antiretroviral therapy to mother
• Elective caesarean section if viral load not fully suppressed (>50 copies)
• If viral load ≥400 consider zidovudine intrapaartum prophylaxis
• Avoid invasive obstetric procedures (eg. amniocentesis, fetal scalp monitoring, fetal scalp blood sampling, episiotomy)
• Neonate needs ARV - low risk cases zidovudine sufficient, high risk cases needs combine HAART - for 4 weeks
• Test PCR at 1 wk, 6 wk, 3 months and test HIV Abs at 18 months
• Formula feeding (avoiding breastfeeding) - highest risk is with mixed breast/formula feeding

Question 16

Managament of obstetric patient with HIV

Answer 16

Preconception: Recommend pre-pregnancy counselling to ensure adequate treatment, low viral load. If fully suppressed viral load and on treatment- chances of transmission to partner are extremely low. If concerns then can be referred to fertility team for consideration of IVF/sperm washing.

• At booking: Appropriate referrals as above
o Booking bloods plus electrolytes, creatinine, liver function, MSU
o Dating scan if uncertain dates
o STI infection screen
o Cervical smear if not done in past year
o Full medical examination
o Arrange MSS1 screening (if desired)
o All women should be offered a Social Worker referral to assess social needs and support services
o Physiotherapy and dietitian services if appropriate

• 12-16 weeks
o MSS1 testing
o Invasive diagnostic testing (CVS or amniocentesis) is probably safe in women with suppressed viral loads. For women with unsuppressed viral loads, there is likely to be risk of vertical transmission. Decisions need to be made on a case by case basis.
o NIPT (Non Invasive Prenatal Testing) may be an alternative and should be offered, but this is not publicly funded.
• 18-20 week:
o Morphology scan
o FBC, electrolytes, creatinine, liver function, MSU  75 g/2 hour glucose tolerance test if on protease inhibitors (lopinavir + ritonavir (Kaletra®), atazanavir, danrunavir) or other risk factors
o Notify the Christchurch Women’s Pharmacist of the identity of the HIV positive woman and her expected delivery date so that supplies of intravenous zidovudine for the woman and oral zidovudine for the baby, can be issued to birthing suite well in advance of the EDD
• 28 weeks
o Fetal growth assessment – scan if concerned
o FBC, electrolytes, creatinine, liver function, MSU
o HIV viral load and CD4 count
o 75 g/2 hour glucose tolerance test (if earlier test negative, or not had testing)
o Anaesthetic review
• 32 weeks
o Fetal growth assessment – scan if concerns
o Repeat bloods and MSU
o HIV viral load, if previous detectable viral load or history of pre-term birth
o Neonatal review and plan completed
• 36 weeks
o Fetal growth scan
o HIV viral load and CD4 count
o Repeat bloods and MSU Infections
Each woman should be assessed at each visit with regards to the possibility of opportunistic infections

Question 17

Side effects of antiretrovirals

Answer 17

• Protease inhibitors (eg. Kaletra® - (lopinavir+ritonavir), atazanavir, darunavir): glucose intolerance and diabetes mellitus, GI intolerance
• Truvada® - (tenofovir + emtricitabine): well tolerated
• Abacavir in combination with lamivudine as Kivexa®: hypersensitivity reaction (HLA B5701 screening helps predict this)

If an HIV positive woman presents with apparent signs or symptoms of pre-eclampsia, cholestasis or liver dysfunction the differential diagnosis should include a check for potential anti-retroviral toxicity.

Question 18

Antenatal complications of HIV

Answer 18

GDM & PET: Glucose impairment and pre-eclampsia have been associated with HAART. Both should be managed in accordance with normal obstetric practice.

Preterm labour: Preterm birth has been identified as a risk for vertical transmission. An HIV positive woman presenting with threatened preterm labour and intact membranes should have triple swabs taken for microbiology. Betamethasone should be administered in keeping with normal obstetric practice. There is no evidence for benefit from use of tocolytics in women with HIV infection. Since women with an unsuppressed viral load are at increased risk of sepsis, tocolysis should be avoided. For women with fully suppressed viral load on HAART the decision to treat with tocolytics should be discussed with the consultant on call. It would be reasonable not to use tocolysis in this setting.

PPROM at 34-37/40: In the event of PPROM after 34 weeks gestation birth should be expedited without delay. Triple swabs should be taken for microbiology and intravenous antibiotics should be prescribed in labour in accordance with the local guidelines on antibiotic prophylaxis in labour. For those women with no other obstetric complication on HAART with a fully suppressed viral load and intending to birth vaginally then induction of labour is the management of choice.

PPROM <34/40: In the event of preterm pre-labour rupture of membranes before 34 weeks gestation the decision to expedite birth will depend on various factors. Women with HIV are at an increased risk of chorioamnionitis.

Question 19

Delivery plan for women with HIV

Answer 19

A full discussion regarding the mode of birth should take place with each woman.

A clear plan must be documented in the notes.

Women whose viral load is less than 50 copies/mL or not detected (fully suppressed) may safely choose a vaginal birth.

Caesarean section does not offer additional benefit to reduce vertical transmission of HIV and should be used for usual obstetric indications- in fact c-section carries higher risk to women with HIV.

Elective Caesarean section is recommended if the viral load is not fully suppressed or if the woman is not on HAART

Ensure to maintain confidentiality whilst in labour

Invasive procedures including use of fetal scalp electrodes and fetal pH sampling, episiotomy and assisted vaginal delivery appear safe in women with a completely suppressed viral load. However, the decision to perform them should be made on a case by case basis. There is no data that suggests an increase in transmission with the use of instrumental delivery but forceps may be preferable

If undetectable viral load- continue antentatal ARVs in labour
If detectable viral load- IV intrapartum Zidovudine to be given

Beware placenta potentially infectious

Question 20

Postnatal care for women with HIV

Answer 20

Women with HIV may be at higher risk of postnatal infection

All maternal medications including antiretrovirals should be continued post-partum at the usual dose times. In some women, antiretroviral medication may be stopped postpartum, but would be continued in those women who require antiretrovirals for their own health. In addition a woman who decides to breastfeed should remain on anti-retroviral therapy. Contraceptive advice should be given.

Question 21

Management of the baby of a HIV positive mother

Answer 21

If the woman has an undetectable viral load and on HAART treatment, then ‘skin to skin’ contact with the mother should be offered as soon as possible after the birth.

The baby should then be bathed at a suitable time following this period of skin to skin. It is important for baby to have a bath prior to any intramuscular injections or heel pricks. Following ‘skin to skin’ time the mother may also need any fluid washed off her skin.

If the woman has an unknown or high viral load then the baby should be bathed immediately after birth prior to skin to skin.

Feeding guidelines National recommendations are that all breastfeeding (including colostrum) should be avoided. If the mother decides to breastfeed despite advice then she should continue ARVs.

Within 6 hours of birth the infant should be administered zidovudine suspension for 4 weeks

High risk for MTCT may require combination HAART.

Check HIV PCR at 1wk, 6 wk, 3 months.
Check HIV Abs at 18 months.

Question 22

A 30 year old primigravid presents at 28 weeks having consumed a product that has recently been recalled because of contamination with listeria. She is extremely anxious for her health and that of her baby.

b. Formulate a detailed response for this patient to address these concerns:

Clinical features (3 marks) 
Perinatal effects (3 marks) 
Management (3 marks)

Answer 22

Clinical features - enquire and educate about these:
• Fever, flu-like illness, general malaise, abdominal/loin pain, back ache, diarrhoea, sore throat, conjunctivitis.
• If severe – ARDS, meningitis, encephalitis, septicaemia. May be asymptomatic (approx. 1/3).

Perinatal effects:
• Transmission is highest in 3rd trimester and has 40-50% mortality for fetus.
• Miscarriage/IUFD, perinatal mortality, PPROM, PTL, chorioamnionitis, meconium stained liquor. Neonatal – pneumonia, meningitis. However, may also have no affect.

Management:

1. Admit to hospital for observation and supportive management.
2. Maternal diagnosis – blood cultures and gram stain and cultures of genital tract (serology unhelpful)
3. Antibiotics – PO amoxycillin/ampicillin if mild. IV amoxycillin/ampicillin and gentamicin if severe (not sensitive to cephalosporins). Duration of 14 days.
4. Consider delivery after steroids if severe (weigh risks of infection vs risks of permaturity).
5. Notifiable disease to Public Health services.

Question 23

A woman who is 18 weeks pregnant has been exposed to chickenpox.

a. What history and investigations would you obtain? (2 marks)

Answer 23

History:
• Had chickenpox as a child or had vaccination?
• When was she exposed?
• What were the symptoms of the person she was exposed to – infectious from 48 hours prior to rash until lesions crusted over
• Duration of exposure and type of contact (household contact, same room, face-to-face?)
• Has she had any symptoms – fever, mylagia, rash?
• PMHx, meds, allergies, smoker.

Investigations:
• Maternal varicella zoster serology - IgG and IgM

Question 24

A woman who is 18 weeks pregnant has been exposed to chickenpox.

b. How would you manage her exposure risk? (4 marks)

Answer 24

• If history of childhood chickenpox – 97-99% predictive of IgG seropositivity – reassure
• If IgG positive – reassure, confirms not susceptible
• If IgG negative then is susceptible– give VZIG – most effective within 96h but still effective up to 10 days after signficant exposure (household contact, same room for 1 hour, face-to-face for at least 5 mins)
• Counsel and consent (human blood product)
• If >96h from exposure then ASID recommends no VZIG but consider oral aciclovir post-exposure prophylaxis if at risk (2nd half of pregnancy, underlying lung disease, immunocompromised, smoker)
• Educate on signs and symptoms of chickenpox and advise to seek medical attention promptly if develops (preferably GP or ED to minimise exposure to other pregnant women)

Question 25

2 weeks later she develops a moderately severe chicken pox infection.

c. List the maternal signs and risks of chicken pox infection. (2 marks)

Answer 25

Maternal signs:

• Prodrome - fever, malaise, mylagia, lymphadenopathy
• Then - pruritic rash that arranges into crops and becomes vesicular – lesions eventually burst and crust over

Risks – Disseminated chickenpox:

• Varicella pneumonia
• Varicella encephalitis
• Hepatitis
• Increased mortality in pregnancy

Question 26

d. Justify the circumstances under which you would give oral or parenteral treatment to the mother (3 marks)

(Varicella at 18/40)

Answer 26

Aciclovir can be commenced if <24 hours sicne onset of rash to reduce the severity/duration of symptoms (Not known to decrease risk of transmission or treat FVS.)
• If no complications: oral dosing 800mg 5 times per day
• If complications (respiratory symptoms, haemorrhagic rash or bleeding, new pocks developing >6 days, persistent fever >6days or neurological symptoms) or immunocompromised: IV dosing 10mg/kg/dose 8 hourly

Question 27

e. What would you explain to the mother about the fetal risk and its management? (4 marks)

Answer 27

Fetal risk:
• Overall risk of fetal varicella syndrome (FVS) is low
• Risk depends on gestation – highest risk is 12-28 weeks but is still only 1.4% % (<12 0.51%, after 28/40- no reported cases of FVS)
• FVS manifested by:
o Skin scarring in dermatomal disribution
o Low birth weight, prematurity
o Eyes – cataracts, microphthalmia
o Limb hypoplasia
o CNS – microcephaly, low IQ, sphincter dysfunction,
o 30% early mortality

Management:
• VZIG and acyclovir do not reduce the risk of development of FVS once the mother has chicken pox
• MFM referral, detailed tertiary USS and counselling
• Signs may not show on USS for 5 weeks post infection
• Consider amnio for VZV PCR if abnormalities on USS – helpful if negative (reassuring), if positive does not correlate with severity of outcome
• If signs present – offer TOP
• If continuing pregnancy – serial growth USS for possible development of IUGR
• Neonatal review for serology, neuro and ophthalmology at birth
• If becomes symptomatic requires supportive cares and may require IV acyclovir