Transcript Rubella in Pregnancy

Infections in Pregnancy
Max Brinsmead MB BS PhD
January 2015
Rubella Infection
Caused by the pleomorphic RNA virus of
the genus Rubivirus
 Infects only human subjects
 In adults and children causes:
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 Mild
fever & malaise
 Generalised fine erythematous rash – rarely
purpuric
 Cervical lymphadenopathy
 Arthralgia
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But will be asymptomatic in 25 – 50%
Rubella in a Pregnant Woman
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Before 12 weeks pregnancy up to 90% risk of:
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Fetus somewhat safer in the 2nd trimester but…
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Miscarriage
Cardiac anomalies
Nerve deafness
Cataracts or retinopathy
Mental retardation
Often multiple defects
Sensineural deafness is the most common problem
In the second half of pregnancy
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Hepatosplenomegaly
Failure to thrive, osteitis
Diabetes, hypothyroidism and GH deficiency
Progressive panencephalitis
= The Congenital Rubella Syndrome
Prevention of Congenital Rubella
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Immunise all children at 12 -15m (MMR)
Test all women who are pregnant (or plan to
conceive) for immunity
Avoid infection if pregnant
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Spread by nasopharyngeal droplets +/- 7 days from the time
of rash
Retest any pregnant woman who is exposed to
the virus
Terminate pregnancy for proven infection
Immunise women postpartum if low titre or non
immune
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Immunisation of a pregnant woman with the live virus is not
recommended but is also not associated with teratogenesis
Varicella
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Caused by Herpes zoster
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Causes
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Chickenpox
Shingles
Fetal varicella syndrome (FVS)
In pregnancy maternal risks of pneumonitis
(10%) are greater than the fetal risks of FVS
(2%)
Fetal Varicella Syndrome
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Greatest risk is maternal infection 13 – 20w
Mental retardation 50%
Skin scarring
Eye defects (micropthalmia, chorioretinitis and
cataracts)
Limb hypoplasia
Bowel/Bladder dysfunction
Intrauterine diagnosis requires amniocentesis or
fetal blood sampling for HZV PCR. Has poor
positive predictive value
Neonatal Varicella
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Risk is greatest if maternal rash occurs 5 days
before delivery and up to 2 days after
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Transmission rate 20 – 60%
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30% neonatal mortality if untreated
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Acyclovir recommended
Maternal Varicella in Pregnancy
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Pneumonitis 10%
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Hepatitis
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Encephalitis
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Acyclovir or similar required
Preventing HSZ in Pregnancy
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Prenatal screening and/or Immunisation
Serum HZV IgG at the 1st antenatal visit
ZIG for non immune women who come into
close contact with Varicella
Prophylactic oral Acyclovir for exposure >20w
Delay delivery >7 days after rash
Neonatal ZIG and Acyclovir for high risk neonate
Immunise health care workers
Exclude those non immune to Varicella from
care of pregnant women for 8 – 21days after
possible infection
Genital Herpes
66% caused by H. simplex Type 2
 33% associated with H simplex Type 1
 Is a latent and recurrent infection in up to
1:5 adults
 ~1:50 women have this virus during
pregnancy
 But most are secondary (or recurrent)
infections
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Even if the woman says she has never had it
before
Neonatal Herpes
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Three subgroups of neonatal infection
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Disseminated disease has 80% mortality
(untreated) and 30% with antiviral agents
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Skin, eye and mouth disease
Encephalitis only
Disseminated disease
And 1:5 risk of long term morbidity in survivors
Risk of death from skin, eye and mouth disease
is 2%
Maternal Herpes
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Primary infection can be disseminated with
encephalitis, hepatitis and skin eruptions
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Is more common in pregnancy because of the mild
immunosupression which occurs
Most infections during pregnancy are secondary
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But recurrences are more common because of
pregnancy-related immunosuppression
Vertical Transmission of Herpes
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Mostly occurs when the fetus contacts infected
genital secretions
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But intrauterine infection and FDIU possible
Neonatal infection is also possible
Disseminated Herpes occurs after primary
maternal infection
 Often
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with premature delivery
Secondary maternal Herpes can cause
 Skin,
eye and mouth disease
 And sometimes isolated neonatal encephalitis
 Because maternal antibodies do not protect the
brain
Risk of Vertical Transmission of
HSV
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With maternal primary Herpes the risk of
neonatal infection is 26 – 56%
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With maternal secondary Herpes the risk
of neonatal infection is 1 – 3%
Diagnosis of Genital Herpes
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Often unrecognised in its recurrent form
Typically localised pruritis and pain
Blister and ulceration
PCR is a sensitive and specific test if
appropriate material is collected
Serum IgG and IgM can be useful in
distinguishing primary and secondary infection
Viral culture
Why Caesarean Section?
A prospective study of 58,000 women in
Washington USA identified 202 of whom 117
delivered vaginally and 85 by CS.
The risk of neonatal sepsis was reduced by 86%
by CS but the RR confidence intervals were
wide (0.02 – 1.12)
This means that it would require 1583
Caesarean sections of patients with secondary
Herpes to prevent one case of neonatal Herpes
(with mortality or morbidity)
Maternal Secondary Herpes
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Weekly cultures are not predictive
Daily Acyclovir from 36 weeks reduces the risk
of
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A recurrence at the time of delivery
Asymptomatic virus shedding
The chance of CS
And should be offered to women who
would elect CS if there was a Herpes
outbreak at the time of labour
Herpes visible at the onset of
labour
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If thought to be a secondary infection then CS is
not mandatory
Requires patient counselling and her choice
should be respected
If there are ruptured membranes then delivery
should be expedited
Fetal trauma should be avoided
The neonatal service should be alerted
Cytomegalovirus
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Proper name is Human Herpesvirus 5
1:100 babies are born with this congenital
infection
1:10 of those infected will show some effect
1:10 of those will have severe mental retardation
CMV is a common cause of mental retardation
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And causes 30% of congenital neural deafness
~40% of women are non immune when pregnant
Health workers and women with children who
bring home CMV are most at risk
Vaccination is not possible
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But trials are currently in progress
Neonatal CMV Syndrome
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Small for dates
Failure to thrive
Hepatospenomegaly
Microcephaly
Cerebral calcifications
Chorioretinitis
Hearing deficits (may occur later in life)
The virus can be detected in urine and saliva
Vertical CMV Transmission
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1-4% of women seroconvert during pregnancy
90% of congenital CMV is due to primary maternal
infection
Risk to the fetus with CMV reinfection is 0.5 – 2%
Reinfection with another strain is also possible
The earlier the infection in pregnancy the greater the risk
Can cause miscarriage in the 1st trimester
Risk to the fetus is small if infection is acquired prior to
pregnancy
Fetal infection cannot be predicted by maternal testing
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but IgG avidity testing emerging as a pointer
Treatment of Intrauterine CMV
Termination of pregnancy is really the only
option
 Should respond to anti viral agents such
as Ganciclovir and Valganciclovir but their
role in pregnant women and the neonate is
unproven
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 Trials
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are underway
Likewise little data on the role of
prophylactic immune gamma globulin
 One
non-RCT trial showed it to reduce fetal risk by
≈60%
Parvovirus
Caused by Parvovirus B19
 Causes
epidemic Fifth Disease or
“Slapped Cheek Syndrome” in pre school
children.
 When intrauterine infection occurs it
affects haemopoeisis. This results in fetal
anaemia and hydrops fetalis.
 However, recovery is usually spontaneous
and complete and there are no long term
sequelae
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Vertical Parvovirus Transmission
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50-66% of pregnant women are Parvovirus
immune
Most infections occur from the mother’s own pre
school child
Spread by droplets c sneezing, coughing
Incubation period is 4 -14 days
Rash occurs on the face but also on hands,
wrists & knees
Maternal symptoms include polyarthalgia, fever
and non specific rash
Fetal Risk
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Transplacental transmission rate is ~30%
Can cause hepatitis and myocarditis
20% risk of fetal death in the 1st trimester
Causes about 3% of miscarriages
Risk of hydrops is greatest in the second
trimester
When a fetal death rate of about 15%
But by 20w the risk of fetal death has fallen to
6%
Treatment of Intrauterine
Parvovirus Infection
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Termination of a pregnancy is not required
Weekly ultrasound monitoring for signs of
hydrops and middle cerebral Dopplers may be
undertaken after documented evidence of
maternal infection
But
most
affected
fetus
will
recover
spontaneously
A small number may require intrauterine
transfusion for severe anaemia
This is ~85% successful
Toxoplasmosis
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Caused by the protozoan parasite Toxoplasma gondi
Is endemic in most societies
And the definitive host is cats
Has a complex life cycle but infectious oocysts can live
for many months in soil
10 – 25% of adults have serologic evidence of previous
infection
In most it causes a mild illness with fever, malaise and
lymphadenopathy
But transplacental infection can cause congenital
disease
Congenital Toxoplasmosis
Mental retardation
 Learning difficulties
 Cerebral calcifications
 Chorioretinitis blindness
 Hydrocephalus
 Epilepsy
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Vertical Transmission
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50% of congenital Toxoplasmosis is due to
eating contaminated meat, mostly pork
Remainder to to contact with cats’ faeces or
contaminated soil
~1:200 women will become infected during
pregnancy
Of these ~1:10 will deliver a baby with
congenital Toxoplamosis
Infection in early pregnancy is less likely to cross
the placenta
But this has more serious effects when it does
Treatment
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Acute infections can be treated with Spiramycin
or sulphadiamine/pyrimethamine
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This will reduce the risk of vertical transmission
by ~50%
Preventing Congenital
Toxoplasmosis
Pregnant women should:
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Cook meat thoroughly and check core
temperature with a cooking thermometer
Prevent contamination of food by uncooked
meat
Avoid contact with cat faeces
Wash or peel vegetables and avoid contact with
soil
Listeriosis
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Caused by Listeria monocytogenes
A motile Gram-positive bacterium
Relatively ubiquitous in the environment
Found in 1 – 15% of human faeces
Infection in animals is common
Human infection is rare except:
 When
immunocompromised
 Pregnant
 Elderly
 Newborn
Listeriosis in Pregnancy
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Fewer than 10 per 100,000 women
Infection may be asymptomatic
But the following symptoms also occur:
(38.2 to 41.20 C and mean of 38.9)
 Malaise
 Flu-like symptoms such as headache and myalgia
 Rarely CNS infection with meningitis or abscess
 Fever
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Transmission risk to the fetus about 50%
Untreated the risk of fetal death is 20 – 30%
Pathognemonic finding is widespread abscesses
& granulomas in the fetus (rare)
Treatment
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Use Ampicillin 2G every 6 – 8 hrs
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This high dose is recommended in order to
cross to the amniotic fluid and membranes in
sufficiently high concentrations
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For penicillin allergy use Bactrim/Septrim
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Sometimes Vancomycin
Prevention
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Aims to reduce a pregnant woman’s exposure to
possible contaminated food sources
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Authorities recommend dietary advice to ALL
pregnant women
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But this has never been tested by RCT
Typical Pregnancy Advice
“Listeria is a very rare infection that is mild in a mother
but can be fatal to the baby in utero. You should
NOT eat the following:
Unpasteurised milk products esp. Soft cheeses,
included feta, Brie, Camembert and ethnic-style
cheeses.
(Hard cheeses, pasteurised, cottage & cheese spreads
are okay)
 Raw seafood
 Uncooked meats and vegetables
 Cold-stored cooked meats and pates
 Milk products stored at >40 C
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Beware of cross contamination from these sources
Wash all fruit and vegetables
Cook foods at recommended temperatures”
Group B Streptococcus
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Group B Streptococcus is the most frequent
cause of severe neonatal infection within 7 days
of birth
Incidence 0.5 – 1.5 per 1000
Risk of death is 10 – 30%
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And there is also morbidity in survivors
15 – 30% of pregnant women are carriers of GBS
(Varies with climate)
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50% of their infants will become colonised during
birth and
1 – 2 % will develop sepsis
Intrapartum antibiotics significantly reduces the
rate of neonatal GBS sepsis
Possible strategies
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Identify and treat high risk patients – no
screening
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Screen all and treat all GBS carriers
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UK (unchanged view in 2012)
USA and many Australian hospitals
Screen all and treat only those with
additional risk factors
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Canada
Is Screening effective?
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There are no RCTs
Observational studies show that intrapartum
antibiotics reduce the risk of neonatal GBS
sepsis by 50 – 95%
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Meta analysis says 86%
Rate of GBS sepsis fell by 33 – 70% in the
US after introduction of universal screening
Is the treatment safe?
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There are no RCTs
Some 15 – 30% of all women require treatment
You have to treat 714 women to prevent one case
of neonatal sepsis
And 7000 women to prevent one neonatal death
Risk of fatal maternal anaphylaxis 1:100,000
This means one maternal death for every seven (7)
babies saved
Unknown risks from non-fatal anaphylaxis
Unknown problems from antibiotic use
HIV in Pregnancy
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Risk of maternal death is increased 6-fold
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Increased risk of poor obstetric outcome
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Concurrent infections including TB
All obstetric causes
Miscarriage
Stillbirth
Pre term birth
IUGR
Mother to Child transmission (MTC) of HIV
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Is the most common means of HIV transmission in the
world
Risk is 25 – 50%
HIV Mother to Child Transmission
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80% occurs during labour
Can be reduced by 50% Caesarean section before
membranes rupture
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But only used where CS is safe in the short and long term
And viral load is >1,000 ml/plasma
A better option is maternal HAART (Highly active
anti-retroviral therapy)
If mother receives triple therapy from <28w, has
elective CS & does not breast feed MTCT is 1-2%
Current WHO Guidelines
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All pregnant women should be tested for HIV
All HIV patients to begin HAART asap
Continue right through VAGINAL DELIVERY
Tail off non-eligible mothers from therapy after they
have stopped breast feeding AND
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Mothers eligible to continue triple therapy to
continue whilst breast feeding PLUS
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Give the infant oral NVP whilst ever mother is
breastfeeding plus one week (up to 12 months)
Give the neonate 6 weeks of AZT and NVP for as long as
the mother is breast feeding
It is hoped that MTC will be 1-2%
Syphilis in Pregnancy
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Typically does not cross the placenta until
>20 weeks
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Fetal effects include…
 Stillbirth
 Intrauterine
growth restriction
 Prematurity
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Neonatal effects include…
 Hepatosplenomegaly
 Pneumonia
 Anaemia
& Jaundice
 Skin lesions
 Osteochondritis
Treatment of Syphilis
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For a mother with proven active Syphilis
Give 3 doses of Benzathine penicillin 2.4 mU weekly
 Erythromycin 500 mg 4 x daily for 15 – 30 days for true
penicillin allergy
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For a neonate
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25,000 IU/Kg Penicillin twice daily for 10 days
Follow up and treat the sexual partner
What is the TORCH test
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TORCH is an acronym commonly used in the
evaluation of stillbirth, IUGR or neonatal
failure to thrive
T = Toxoplasmosis
O = Other (includes HIV, Syphilis etc)
R = Rubella
C = Cytomegalovirus
H = Herpes (simplex and varicella)
Typically serum IgG and IgM for these
infections repeated after 3w
Best regarded as a screening test only
In Summary
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Rubella
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Cytomegalovirus
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A common cause of congenital deafness & mental
retardation but there is little we can do about it
Herpes simplex
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90% risk of fetal damage in the 1st trimester
Common but most genital Herpes in pregnancy is secondary
and there is only a 1-3% risk of vertical infection
Varicella
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The greatest risk is to the mother (10% severe infection)
whilst the overall risk of FVS is 2%
In Summary
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Toxoplasmosis
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Routine dietary advice to pregnant women may be of value
Listeriosis
Think about the possibility if a pregnant woman presents with
high fever etc.
 Routine dietary advice may be of value
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HIV and Syphilis
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Diseases of developing countries
Group B Streptococcus
Up to 20% of women are GBS carriers but only 1:1000
babies are affected by this organism
 Screening and intrapartum antibiotics practised in most
Australian hospitals
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