1. Infections in Pregnancy
Max Brinsmead MB BS PhD
January 2016

2. Rubella Infection
Caused by the pleomorphic RNA virus of the genus Rubivirus
Infects only human subjects
In adults and children causes:
Mild fever & malaise
Generalised fine erythematous rash – rarely purpuric
Cervical lymphadenopathy
Arthralgia
But will be asymptomatic in 25 – 50%

3. Rubella in a Pregnant Woman
Before 12 weeks pregnancy up to 90% risk of:
Miscarriage
Cardiac anomalies
Nerve deafness
Cataracts or retinopathy
Mental retardation
Often multiple defects
Fetus somewhat safer in the 2nd trimester but…
Sensineural deafness is the most common problem
In the second half of pregnancy
Hepatosplenomegaly
Failure to thrive, osteitis
Diabetes, hypothyroidism and GH deficiency
Progressive panencephalitis
= The Congenital Rubella Syndrome

4. Prevention of Congenital Rubella
Immunise all children at m (MMR)
Test all women who are pregnant (or plan to conceive) for immunity
Avoid infection if pregnant
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
Immunisation of a pregnant woman with the live virus is not recommended but is also not associated with teratogenesis

5. Varicella Caused by Herpes zoster Causes
Chickenpox
Shingles
Fetal varicella syndrome (FVS)
In pregnancy maternal risks of pneumonitis (10%) are greater than the fetal risks of FVS (2%)

6. Fetal Varicella Syndrome
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

7. Neonatal Varicella
Risk is greatest if maternal rash occurs 5 days before delivery and up to 2 days after
Transmission rate 20 – 60%
30% neonatal mortality if untreated
Acyclovir recommended

8. Maternal Varicella in Pregnancy
Pneumonitis 10%
Hepatitis
Encephalitis
Acyclovir or similar required

9. Preventing HSZ in Pregnancy
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

10. 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
Even if the woman says she has never had it before

11. Neonatal Herpes Three subgroups of neonatal infection
Skin, eye and mouth disease
Encephalitis only
Disseminated disease
Disseminated disease has 80% mortality (untreated) and 30% with antiviral agents
And 1:5 risk of long term morbidity in survivors
Risk of death from skin, eye and mouth disease is 2%

12. Maternal Herpes
Primary infection can be disseminated with encephalitis, hepatitis and skin eruptions
Is more common in pregnancy because of the mild immunosupression which occurs
Most infections during pregnancy are secondary
But recurrences are more common because of pregnancy-related immunosuppression

13. Vertical Transmission of Herpes
Mostly occurs when the fetus contacts infected genital secretions
But intrauterine infection and FDIU possible
Neonatal infection is also possible
Disseminated Herpes occurs after primary maternal infection
Often 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

14. Risk of Vertical Transmission of HSV
With maternal primary Herpes the risk of neonatal infection is 26 – 56%
With maternal secondary Herpes the risk of neonatal infection is 1 – 3%

15. Diagnosis of Genital Herpes
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

16. 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)

17. Maternal Secondary Herpes
Weekly cultures are not predictive
Daily Acyclovir from 36 weeks reduces the risk of
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

18. Herpes visible at the onset of labour
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

19. Cytomegalovirus 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
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
But trials are currently in progress

20. Neonatal CMV Syndrome 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

21. Vertical CMV Transmission
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
but IgG avidity testing emerging as a pointer

22. 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
Trials 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%

23. 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

24. Vertical Parvovirus Transmission
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 days
Rash occurs on the face but also on hands, wrists & knees
Maternal symptoms include polyarthalgia, fever and non specific rash

25. Fetal Risk 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%

26. Treatment of Intrauterine Parvovirus Infection
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

27. Toxoplasmosis 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

28. Congenital Toxoplasmosis
Mental retardation
Learning difficulties
Cerebral calcifications
Chorioretinitis blindness
Hydrocephalus
Epilepsy

29. Vertical Transmission
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

30. Treatment
Acute infections can be treated with Spiramycin or sulphadiamine/pyrimethamine
This will reduce the risk of vertical transmission by ~50%

31. Preventing Congenital Toxoplasmosis
Pregnant women should:
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

32. Listeriosis 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

33. Listeriosis in Pregnancy
Fewer than 10 per 100,000 women
Infection may be asymptomatic
But the following symptoms also occur:
Fever (38.2 to C and mean of 38.9)
Malaise
Flu-like symptoms such as headache and myalgia
Rarely CNS infection with meningitis or abscess
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)

34. Treatment Use Ampicillin 2G every 6 – 8 hrs
This high dose is recommended in order to cross to the amniotic fluid and membranes in sufficiently high concentrations
For penicillin allergy use Bactrim/Septrim
Sometimes Vancomycin

35. Prevention
Aims to reduce a pregnant woman’s exposure to possible contaminated food sources
Authorities recommend dietary advice to ALL pregnant women
But this has never been tested by RCT

36. 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
Beware of cross contamination from these sources
Wash all fruit and vegetables
Cook foods at recommended temperatures”

37. Zika Virus
Caused by a Favivirus related to yellow fever, dengue, West Nile and Japanese encephalitis
First noted in central Africa in monkeys in 1947, but appeared in Pacific Islands in 2007, then noted to be spreading as a pandemic from South towards North America in 2014
Transmitted by mosquitoes mostly Ae. aegypti
This mosquito found only in far N Queensland

38. Zika Virus Infection Causes a mild febrile illness in adults Diagnosis
Begins with headache
Maculopapular rash (variable)
Myalgia and Arthralgia
Conjunctivitis
Diagnosis
ELISA for IgM and IgG
Some cross reactivity with dengue
PCR for acute phase viral RNA

39. Zika Virus in Pregnancy
Apparent association with transplacental or perinatal mother to infant transmission and the development of fetal microcepahy and brain calcifications
Transmission Risk – UNKNOWN
American CDC recommends that any woman who has travelled to a known endemic area and who has two or more symptoms should be tested for ZV IgG
Monitor fetus with ultrasound and
Refer to a Perinatal Specialist Unit for management
No treatment available

40. Prevention Avoid mosquito bites
Pregnant women should avoid travel to areas known to harbour Zika Virus
Check current maps and guidelines
Avoid mosquito bites
Very low risk of transmission in Australia as most areas do not have the appropriate species of mosquito that would act as a vector

41. Group B Streptococcus
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%
And there is also morbidity in survivors
15 – 30% of pregnant women are carriers of GBS (Varies with climate)
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

42. Possible strategies
Identify and treat high risk patients – no screening
UK (unchanged view in 2012)
Screen all and treat all GBS carriers
USA and many Australian hospitals
Screen all and treat only those with additional risk factors
Canada

43. Is Screening effective?
There are no RCTs
Observational studies show that intrapartum antibiotics reduce the risk of neonatal GBS sepsis by 50 – 95%
Meta analysis says 86%
Rate of GBS sepsis fell by 33 – 70% in the US after introduction of universal screening

44. Is the treatment safe? 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

45. HIV in Pregnancy Risk of maternal death is increased 6-fold
Concurrent infections including TB
All obstetric causes
Increased risk of poor obstetric outcome
Miscarriage
Stillbirth
Pre term birth
IUGR
Mother to Child transmission (MTC) of HIV
Is the most common means of HIV transmission in the world
Risk is 25 – 50%

46. HIV Mother to Child Transmission
80% occurs during labour
Can be reduced by 50% Caesarean section before membranes rupture
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%

47. Current WHO Guidelines
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
Give the infant oral NVP whilst ever mother is breastfeeding plus one week (up to 12 months)
Mothers eligible to continue triple therapy to continue whilst breast feeding PLUS
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%

48. Syphilis in Pregnancy Fetal effects include… Neonatal effects include…
Typically does not cross the placenta until >20 weeks
Fetal effects include…
Stillbirth
Intrauterine growth restriction
Prematurity
Neonatal effects include…
Hepatosplenomegaly
Pneumonia
Anaemia & Jaundice
Skin lesions
Osteochondritis

49. Treatment of Syphilis Follow up and treat the sexual partner
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
For a neonate
25,000 IU/Kg Penicillin twice daily for 10 days
Follow up and treat the sexual partner

50. What is the TORCH test
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

51. In Summary Rubella Cytomegalovirus Herpes simplex Varicella Zika Virus
90% risk of fetal damage in the 1st trimester
Cytomegalovirus
A common cause of congenital deafness & mental retardation but there is little we can do about it
Herpes simplex
Common but most genital Herpes in pregnancy is secondary and there is only a 1-3% risk of vertical infection
Varicella
The greatest risk is to the mother (10% severe infection) whilst the overall risk of FVS is 2%
Zika Virus
Risk of microcephaly UNKOWN

52. In Summary Toxoplasmosis Listeriosis HIV and Syphilis
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
HIV and Syphilis
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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