Intra-uterine and perinatal

infection.

Dr. D. Keady.
Consultant Microbiologist
27/10/2021
 Intra-uterine and perinatal
infection.
 Why are pregnant women, foetus and
neonate particularly vulnerable to
infection?

 What are the main infections in these

groups?

 How to diagnose, treat and prevent

infection in this population.
 Pregnant women are more
vulnerable to infection as
• Induced immunosuppressed state.
• +/- impaired glucose tolerance.
• Hormonal and physical changes – pregnant uterus
places pressure on abdominal organs which may
cause renal tract dilation.
 What infections during
pregnancy?
• More susceptible to infection generally but
especially:
• Urinary tract infections (UTI)
• If membranes ruptured – then risk of ascending
infection (chorioamnionitis)
• Influenza and viral infections tend to be more severe.
• Emerging threats e.g. zika virus; SARS-CoV-2
Maternal infection – Assess using IMEWS: Irish
Maternity Early Warning System:

≥2 of the SIRS criteria: And suspect infection:

 Temp. ≥38℃ or <36℃  Take:

 Resp. rate >20 breaths/min  Cultures

 Heart rate >100 beats/min  FBC +/- lactate
 White blood cell count >16.9 or  Urine output chart
<4 ∗10^9/L
 Bedside glucose >7.7mmol/L
 Give:
 Acutely altered mental status
 Oxygen
 IV fluids
 IV antibiotics (GAPP app)
 Preventative measures during
pregnancy:
• General advice re - foods to avoid; fridge
temp.
• Vaccination:
• COVID-19.
• Influenza (inactivated) - All pregnant women at any stage of
pregnancy. (Immunisation could prevent 1-2 hospitalisations/1,000 pregnant women)
• Pertussis (available as Tdap – tetanus/diphtheria/acellular pertussis
vaccine) Offered during weeks 27 - 36 gestation in each pregnancy, to
protect mother and infant. Tdap can be given at any stage in pregnancy
although this may be less effective in providing passive protection. Tdap
should be offered in the week after delivery if not vaccinated during
pregnancy.
Infection in the foetus and
neonate
• Congenital infection
• Perinatal infection
• Post-natal infection
 Congenital infections:

 Often mild/no apparent Common features:

maternal infection.
 Wide range of severity in
the baby.
Similar clinical presentation. • Rash

 Serological diagnosis.
 May have long term
sequelae if undiagnosed.
• Thrombocytopenia
• Ear and or eye
abnormalities
•
Cerebral abnormalities
• Hepatosplenomegaly;
hepatitis; jaundice
 Screening in pregnancy

Condition (Important - frequency and/or severity; Known epidemiology, incidence, prevalence and natural history)


Test (simple, safe, precise and validated screening test; acceptable to users; agreed policy on further diagnostic investigation/choices).


Intervention (effective intervention; evidence that intervention leads to better outcomes compared with usual care).


Screening programme (The complete screening programme is clinically, socially and ethically
acceptable; The benefit gained should outweigh any harm e.g. overdiagnosis, overtreatment, false positives, false reassurance, uncertain
findings, complications. Effective; Value for money. Information provided must be useful and understood by those being screened).


Implementation criteria (Plan for managing and monitoring the screening programme with an agreed set
of quality assurance standards; Adequate staffing and facilities for testing, diagnosis, treatment and programme management prior to the commencement of
the programme)
 Congenital infections - causes
 Those we screen for:  Those that are not
 Hepatitis B included in routine
 HIV screening, e.g.
 Syphilis
 Toxoplasmosis
 Herpes group viruses
 Rubella

 +/- VZV (not part of screening

– e.g. CMV, HSV
 Parvovirus
programme but exposure history
 Others
sought & testing offered if sig.
exposure and no previous
infection)
What infections are pregnant
women screened for?
 Hepatitis B (virus)
 HIV (virus)

 Syphilis (bacterium)
 Rubella (virus)

 History of chickenpox (VZV) is asked about. If

negative, patient is advised to contact doctor if
contact with person with chickenpox or
shingles.
 Hepatitis B – DNA virus
 Vertical transmission is
commonest mode of
transmission worldwide.
 90% develop chronic

infection with risk of

cirrhosis and HCCa
compared to 10% if
acquired in adulthood.
 Most infection transmitted

around delivery.
 Hepatitis B antenatal
screening
 Screen for HBV surface antigen (HBVsAg)98 .
new pregnant carriers 2012; 59 in 2017.
 If detected, full markers and viral load.
 Notifiable.
 Household contacts screened & vaccinated if

not immune.
 Hepatitis B Immunoglobulin (HBIG) within 24

hours of birth & vaccine at birth 0, 2, 4 & 6

months of age. (4 doses) (usually 3 doses of 6 in 1 (DTaP/IPV/Hib/Hep B)
http://www.hse.ie/eng/health/immu
nisation/hcpinfo/guidelines/

Only available online

Screening in pregnancy
 Hepatitis B (virus)
 HIV (virus)

 Syphilis (bacterium)
 Rubella (virus)

 History of chickenpox (VZV) is asked about. If

negative, patient is advised to contact doctor if
contact with person with chickenpox or
shingles.
 HIV
 Antenatal HIV testing in Ireland since 1999.

Aims:
 To identify those affected so can get optimal care
 To decrease incidence of mother-child

transmission of infection
 To potentially decrease risk of transmission to

sexual partners.
If found to be HIV positive

 Treatment with anti-retroviral drugs

started.
 C-section delivery.

 Avoid breastfeeding in developed world.

In developing countries, not

breastfeeding is a greater risk to the child
– encouraged.
 Decreasing HIV transmission –
intervention & approx
transmission rate:
 None 25 – 30%
 Avoid breast feeding 12-15%
 AZT monotherapy 6-8%
 Pre-labour C-section 2%
 Pre-labour C-section & AZT <2%
 Combination ART +/- C section:
 VL at delivery <400copies/ml 1%
 VL at delivery <50copies/ml
HIV testing post-partum
 Baby born to HIV positive mother:
 IgG will be positive due to maternal

transfer across placenta – usually gone

by 9/12 but can occasionally persist up
to 15 months.
 HIV viral load.
 Repeat testing over time.
https://www.hpsc.ie/a-z/hivandaids/hivdataandreports/HIV_2018_finalrev.pdf

Mother to child transmission

There were four cases where the probable route of transmission was attributed to
Mother to Child Transmission (MTCT). Three of these cases were adults and
one was a paediatric case. All four cases were born outside Ireland.
The Rainbow Clinic in the Our Lady’s Children’s Hospital in Crumlin reported that
there were 77 babies born to HIV infected mothers in Ireland during 2018. At
the time of this report, (based on serial HIV PCR testing); 76 infants are not
infected, and one remains of indeterminate status (i.e. does not meet the
criteria for HIV infection and are <18 months at time of test).
Screening in pregnancy:
 Hepatitis B (virus)
 HIV (virus)

 Syphilis (Treponema pallidum a bacterium)

 Rubella (virus)

 History of chickenpox (VZV) is asked about. If

negative, patient is advised to contact doctor if
contact with person with chickenpox or
shingles.
 SyphilisT. pallidum
(bacterium)
• Untreated maternal syphilis in first 2 years
after infection causes:
• foetal/perinatal death (20%)
• Preterm delivery (20%)
• Congenital syphilis (40%)
At birth - may be asymptomatic or multi-system involvement e.g.
hepatosplenomegaly; lymphadenopathy; mucocutaneous lesions;
osteochondritis; haemolytic anaemia; thrombocytopenia
or present much later >2 years: bones, joints, CNS, teeth, eyes & skin;
5-10 years or longer: interstitial keratitis; VIII nerve deafness
 Syphilis – T. pallidum – a spirochaete

 High risk pregnancies may be rescreened

in 3rd trimester.
 Positive results need confirmation and

previous treatment details.

 Penicillin is treatment of choice.

 Refer to GUM/ID service

What infections are pregnant
women screened for?
 Hepatitis B (virus)
 HIV (virus)

 Syphilis (bacterium)
 Rubella (virus)

 History of chickenpox (VZV) is asked about. If

negative, patient is advised to contact doctor if
contact with person with chickenpox or
shingles.
 Rubella (RNA virus)
 German measles.
 Self-limiting febrile illness and rash in children.

Often more severe in adults.

 Droplet spread – high infectivity.
 Notifiable.
 NB lab confirmation – serology or oral secretions.
 Included in MMR vaccine (live vaccine – do not

give in pregnancy and delay pregnancy for 1

month after giving).
 Congenital Rubella Syndrome

• Greatest risk of transmission in 1st 11/40: >90%

and greatest risk of severe congenital infection
affecting hearing, heart, eye and brain.
• Risk of transmission and risk of damage to foetus
decreases after this:
16-20/40 - 45% transmission risk; deafness only.
>20/40 – no increased adverse foetal outcome.
(Main developmental stage over)
 Congenital Rubella syndrome.

 Eyes: cataracts; microphthalmia;

glaucoma; retinopathy.
 Heart: PAS; PDA; ASD/VSD.
 Ears: deafness.
 Brain: microcephaly;
meningoencephalitis; developmental delay.
 Other: growth retardation; bone
disease; hepatosplenomegaly;
thrombocytopenia; rash.
 Rubella blood tests
 Booking blood: mother IgG: If <10 IU/ml, offer
vaccination post-partum.
If indicated, check baby for IgG and IgM:
 IgG can cross placenta from mother.
 IgM can’t cross placenta – if positive, means baby

has been infected in-utero.

 Urine PCR
 If congenital rubella confirmed, urine and oral

secretions are infectious for up to one year – need

to isolate baby if in hospital.
Rubella notifications
https://ndsc.newsweaver.ie/epiinsight/94
ae5pg2xzb10gkzp9yxn5?a=1&p=546305
59&t=17517774
Adequate national MMR uptake has not
yet been achieved - Ireland remains
at risk of exposure to imported cases
of rubella through international travel
and migration.
Important that comprehensive
surveillance and public health follow-
up continue to effectively detect and
respond to notified rubella cases in a
timely manner.
MMR is a highly effective and safe
vaccine against rubella and its uptake
should continue to be promoted in
order to ensure that the elimination of
rubella in this country is sustained.
Infections that are not part of
routine screening programme
 Herpes group viruses
 Toxoplasmosis

 Parvovirus B19
Herpes family viruses

 ds DNA viruses
 VZV – varicella zoster virus

 HSV – herpes simplex virus

 CMV - cytomegalovirus
 VZV - chickenpox

History enquired at booking:

If had chickenpox, is immune.
If no history of chickenpox, advised to avoid those
with chickenpox (or shingles) if possible.
If significant exposure, test blood for VZV IgG:
If detected – already immune – reassure.
If not detected and exposure ≤ 10 days – give VZIg to
attenuate disease in mother. May still develop
chickenpox. Isolate in healthcare setting.
 VZV

 Chickenpox in pregnancy can be more

severe than in non-pregnant adults.
 If signs of pneumonia – admit; isolate; IV

aciclovir.
 Foetal varicella syndrome: 2% if in 1 st 20/40

 Limb deformities; skin scarring;

Chorioretinitis
VZV in the neonate

 Most risk: maternal chickenpox 5/7

before to 2/7 after birth.
 VZIg given at birth

 Aciclovir
 HSV 1 & 2
 HSV 1- 1ry infection may be asymptomatic or
cause severe painful ulceration of throat &
mouth usually. Reactivation causes cold sores.
 HSV 2- 1ry infection – painful ulceration of GU

tract usually.
 Neonatal herpes – can cause a severe systemic

viral infection with high morbidity and

mortality, usually acquired at or around time of
delivery.
 Neonatal herpes

 Encephalitis
 Disseminated infection – CNS, skin, eyes

 Localised eye, skin or mouth disease.

 May be HSV2 from maternal genital tract

especially if 1ry infection in 3rd trimester or

HSV1.
 Aciclovir

 C-section delivery
 CMV

 1ry infection: asymptomatic or 'flu-like illness.

 Infection in pregnancy can result in intrauterine

infection but foetal damage is relatively

infrequent.
 If occurs, can cause IUGR; neurological

impairment; chorioretinitis; hearing loss.

 Diagnosis by serology but can be difficult.

 No effective treatment/vaccination available

Infections that are not part of
routine screening programme
 Herpes group viruses
 Toxoplasmosis
 Parvovirus B19
 Zika virus
 Toxoplasma gondii

 Toxoplasmosis
 Protozoan parasite
 Cat=definitive host
 Toxoplasmosis

 Often asymptomatic or mild 'flu-like illness in

healthy non-pregnant people.
 Pregnancy: can cross placenta & cause serious

developmental abnormalities.60% asymptomatic at birth but may

have long term sequelae – deafness, low IQ, microcephaly. 40% symptomatic at birth:
choroidoretinitis; microcephaly/ hydrocephalus; I-C calcification; seizures; jaundice;
hepatosplenomegaly.
 If diagnosed in pregnancy, treatment of
mother and baby after birth may attenuate
serious damage.
 Toxoplasmosis – avoiding
infection:
 Wash hands before handling food.
 Thoroughly wash all fruit and vegetables.

 Thoroughly cook raw meats and ready-prepared

chilled meals.
 Wear gloves and thoroughly wash hands after

handling soil/gardening.
 Avoid cat faeces in cat litter or soil.
 Parvovirus B19/Erythrovirus

 “Slapped cheek syndrome”

 Adults +/- acute arthritis; targets RBCs eg

aplastic crisis esp. if immunodeficiency or

haemolytic anaemia.
 Infection in pregnancy: transplacental

transmission (1/3) with hydrops foetalis and

death (esp first 20/40).
 Early diagnosis may allow intervention with

intrauterine transfusion.
Zika virus
 Coronavirus – SARS-CoV-2 – COVID 19

Corona viruses: large and diverse group.

• Many animal viruses.
• 7 CoVs now known to infect humans:
• 4 CoVs (HKU1, NL63, OC43, and 229E)
cause mild to moderate URTI; 10-30%
common cold; viral pneumonia
occasionally.
• 2 CoVs previously associated with
outbreaks of severe respiratory disease:
SARS-CoV China 2003 & MERS-CoV Saudia
Arabia 2012 (sporadic infection now).
• 2019n-Cov China 2019 – commonly known
as COVID-19 now.
 COVID 19 in pregnancy

• Pregnant women probably not more likely to contract COVID-19

but at significantly higher risk of severe illness, esp. in 3rd
trimester, compared with non-pregnant women.
• COVID-19 in pregnancy: more likely to be admitted to hospital, to
need care in an intensive care unit (ICU), with higher morbidity
and mortality. Most women admitted to ICU with severe COVID-
19 were not vaccinated.
• COVID-19 morbidity in pregnancy: higher risk of preterm birth,
high blood pressure, postpartum haemorrhage and stillbirth than
those who are not infected with COVID-19.
• COVID-19 does not appear to cross the placenta or directly affect
the infant in-utero; placentitis rarely described in acute infection.
COVID 19 in pregnancy

• Currently - screening all patients on

admission to hospital & at 72 hours.
• Vaccination history for patient and visitor.
• Recommend and encourage vaccination
with mRNA vaccine at any stage of
pregnancy.
https://rcpi-live-cdn.s3.amazonaws.com/wp-content/uploads/2021/10/QA-for-preg
nant-or-breastfeeding-women-about-COVID-19-vaccination_October2021.pdf
Congenital infections summary
 Screen for:  Based on clinical
 Hepatitis B features, may need
 HIV
to consider:
 Syphilis
 Herpes viruses:
 Rubella  VZV; HSV; CMV
 Toxoplasmosis
 Parvovirus B19

 Zika virus

 Corona virus(COVID19)
 Neonatal sepsis
 Infections acquired around time of birth
(perinatal) or early neonatal period.
 Immature host defence mechanisms - if

premature, an immature defence system.

 Less time for maternal IgG to cross placenta.
 Thin skin.

 Increased need for neonatal ICU care which also

increases risk of infection.

Neonates are very vulnerable to
infection.
Neonatal sepsis
 Early onset – related to delivery; usually
acquired from mother.
 Late onset – may be acquired from

mother but other factors important –

e.g. cross transmission of infection from
other babies, staff hands, equipment
etc. in nursery.
 Early-onset sepsis:
 Clinical features – often non-specific –
grunting; off-feeds; poor handling etc.
 Cultures: blood; +/- CSF

 Management: supportive - ventilation;

circulation; nutrition; antibiotics=

 Empiric treatment with penicillin &

gentamicin.
Early-onset sepsis - causes
 Group B streptococci
 E. coli
 Listeria monocytogenes
 Late onset sepsis – causes
 Group B streptococci
 E. coli

 Listeria monocytogenes

 Coag. neg. staphylococci

 S. aureus

 Enterococci

 Gram negatives – Klebsiella spp. /Enterobacter

spp. /Pseudomonas aeruginosa

 Candida
Neonatal bacterial infections:
 Group B streptococci
 E. coli
 Listeria monocytogenes
Group B streptococci
 Gram positive coccus.
 Chains.
 Beta-haemolytic.
 Lancefield Group B
Group B Streptococcus (GBS) –
gram positive coccus
 About 25% pregnant women colonised
with GBS.
 About 25% babies born to carrier

mothers become colonised.

 Irish incidence: 0.6/1000 live births.

 Screening not currently recommended in

Ireland/UK (RCOG 2017)

 GBS – early onset disease
 More common than late-onset GBS.
 Greater morbidity and mortality.

 Risk factors: prematurity; premature and/or

prolonged rupture of membranes; maternal

fever in labour; multiple birth; previous baby
with GBS; GBS bacteriuria in this pregnancy;
GBS in this pregnancy.
 Offer Intra-partum Antibiotic Prophylaxis (IAP)

- penicillin.
 GBS -early onset sepsis

 Clinical features – often non-specific –

grunting; off-feeds; poor handling etc.
 Send blood cultures; +/- CSF

 Management – supportive – ventilation;

circulation; nutrition; antibiotics=

 Empiric treatment with penicillin &

gentamicin.
 GBS – late onset

 Acquired after birth from mother or other

babies/staff in nursery setting.
 Usual better outcome than early onset

disease.
 Treatment – penicillin & gentamicin.
 Neonatal bacterial infections:
 Group B streptococci
 E. coli
 Listeria monocytogenes
E. coli
 Gram negative rod.
 Bacteraemia.

 Meningitis.

 UTI.

 Diagnosis: cultures of blood, urine, CSF

etc.
Neonatal bacterial infections:
 Group B streptococci
 E. coli
 Listeria monocytogenes
 Bacteria widespread in
the environment:
animals, soil,
vegetables.
Also in food – e.g.
unpasteurised milk;
yoghurts; cheeses
especially soft cheeses
e.g. Brie etc.
Pregnant women asked
to avoid these foods.
Ensure fridge temp. kept
at 3ºC or lower

Listeria monocytogenes
(gram positive rod)
 Listeriosis

 Infection in early pregnancy – likely foetal

loss.
 Later pregnancy infection – very sick infant

– abscesses and granulomas in multiple

organs e.g. Lungs, liver, brain - high
mortality.
 If acquired peripartum – presents later often

with meningitis.
 Listeriosis

 Diagnosis:
 Culture of blood, CSF, amniotic fluid etc.
 Treatment:
 Amoxicillin & gentamicin.
 **Resistant to 3rd gen cepahalosporins**
 Conjunctival eye infection post-
partum.
Causes:
 Staphylococcus aureus -commonest local

cause but need to consider

Ophthalmia neonatorum:
 Neisseria gonorrhoeae – gonococcus –

usually presents day 2-3 post-partum.

 Chlamydia trachomatis -usually presents day

7-10 post-partum
 Ophthalmia neonatorum

 N. gonorrhoeae – needs systemic antibiotics.

Parents need referral to GUM.
 C. trachomatis – risk of pneumonia if untreated.

Also needs systemic antibiotics. Parents need

referral to GUM.
 Intrauterine & perinatal
infections
 Pregnant women more susceptible to infection
due to altered immunity, hormonal and
physical factors.
 Foetus/neonate susceptible to infection due to

immature immune system.

 Congenital infections: hepatitis B; HIV;

syphilis; rubella; others e.g. herpes group

viruses; toxoplasmosis, parvovirus etc. New
threats…
 Neonatal sepsis: GBS; E. coli; Listeria; etc.