Maternal infections Armando Hasudungan

Overviews

Maternal infections is a broad term for any infection that is acquired by a pregnant woman antepartum, intrapartum or postpartum. These infections may have detrimental impacts on the mother and the foetus/newborn.¹Maternal infections covered in this page include TORCH infections as well as Group B Streptococcal infection and chorioamnionitis.

TORCH infections are a group of congenital infections that can be passed on from the mother to the foetus or newborn. TORCH stands for:

T: toxoplasmosis
O: Other
- Syphilis, HIV, Hepatitis B, VZV, Parvovirus B19
R: rubella
C: cytomegalovirus
H: herpes simplex virus

Highest risk to fetus if infection occurs in the first trimester.

Toxoplasmosis²

Organism: Toxoplasma gondii – protozoan parasite
Causes
- Consumption of raw/inadequately cooked meat infected with cysts
- Consumption of food/water contaminated by cat faeces
Transmission/life cycle³
- Incubation period: 5-23 days
- Main host: domestic cats
  - Cats acquire T.gondii through consuming small infected rodents and birds, or cat faeces consumption
  - The parasite infects the intestinal tract allowing for the sexual stage of the life cycle. Oocytes are then excreted in faeces for 10-20 days
Maternal clinical manifestations
- Usually asymptomatic
- Rarely: lymphadenopathy, chorioretinitis
Foetal/neonatal clinical manifestations
- Prematurity
- Neurological triad: hydrocephalus, chorioretinitis, periventricular calcifications
- Mental retardation
- “blueberry” rash
- Jaundice
- Hepatosplenomegaly
- Myocarditis
- pneumonitis
Investigations
- Ix for maternal infection: Serum IgG measurement – serial measurements
- Ix for foetal infection: PCR on amniotic fluid
- If positive
  - Ultrasound: to detect any foetal abnormalities
  - Amniocentesis for PCR at 18-20 weeks gestation, or if >3 weeks after maternal infection identified
Management⁴
- Spiramycin (brand name – rovamycine)
- If <12 weeks gestation: if amniocentesis PCR positive, consider counselling regarding termination of pregnancy
- If 28-42 weeks: if spiramycin unavailable → atovaquone or azithromycin
Prevention
- Avoid raw/undercooked meat
- Wash hands thoroughly after gardening or handling raw meat handling cat litter OR delegate task to others in family,
- Wash fresh produce thoroughly before consuming

Syphilis⁵

Overview: syphilis is a common STI, though if left untreated in a pregnant woman, she can transmit this infection to the unborn infant.
Organism
- Treponema pallidum
Transmission⁶
- Unprotected oral, vaginal or anal sex with a person who has become infected
- Skin-to-skin contact with syphilis rash
Risk factors
- Maternal drug abuse
- Homelessness
- Low SES
- Sex with multiple partners
- Failure to receive prenatal care, STI testing
Maternal clinical manifestations
- Primary syphilis: painless chancre
- Secondary syphilis: fever, generalised lymphadenopathy, maculopapular rash
- Late latent syphilis: asymptomatic
- tertiary syphilis: gumma, neurosyphilis and cardiovascular syphilis
Foetal/neonatal clinical manifestations
- most asymptomatic at birth
- early stages: rhinitis, maculopapular rash, lymphadenopathy
- later:
  - facial changes: frontal bossing, saddle nose, short maxilla
- anaemia and thrombocytopaenia
- Miscarriage
- Stillbirth
- Prematurity
- Low birth weight
- Neonatal death
- Hepatomegaly
Investigations⁵
- Syphilis serology: all pregnant women
  - Routine antenatal screening “booking bloods”: <10 weeks gestation
  - Repeat at 26-28 and 36 weeks gestation
- If lesions/chancre present → dry swab syphilis PCS and serology
Management⁵
- Dependent on the stage of syphilis
- Infectious syphilis: benzathine benzylpenicillin 1.8g IM once only
- Late latent or unknown duration: benzathine benzylpenicillin IM 1.8g weekly for 3 weeks
Prevention
- Using barrier contraception (condoms)

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HIV^{7, 8}

Overview
- Transmission of HIV from mother to child can occur antepartum, intrapartum, or postpartum (breastfeeding). Majority of cases occur intrapartum
Organism: Human immunodeficiency virus
Transmission: exchange of bodily fluids: blood, semen, vaginal fluids, breast milk
Maternal clinical manifestations⁹
- Oral thrush
- Recurrent fever
- Night sweats
- Weight loss
infant clinical manifestations⁸
- Oral thrush
- Failure to thrive
- Lymphadenopathy
- Hepatosplenomegaly
- Ear and sinus infections
- URTI
- Diarrhoea
- Recurrent infections
Investigations⁷
- Booking bloods: HIV
- Baseline bloods: eLFTs, anylase, HLA, FBC,
- CD4 cell count, HIV viral load, HIV resistance testing
- Consider low vaginal swab for other STIs
Management⁷
- Strongly discourage breastfeeding
  - Consider cabergoline (lactation suppressor)
  - prescribe anti-retroviral therapy: with consultation with infectious disease
  - for baby: zidovudine prophylaxis within 6-12 hours of birth, continue for 4 weeks

Hepatitis B

Overview: infection which causes both acute and chronic liver disease. Infants may be infected with this maternal infection primarily during the intrapartum period.
Organism: hepatitis B virus
Transmission¹⁰:
- broken or penetrated skin, mucosal contact with bodily fluids: blood, saliva, vaginal fluids and breastmilk. Unprotected sex, use of contaminated syringes for illicit drug use, tattooing, body piercing, needle stick injuries
- Risk of perinatal transmission is dependent on the level of hep B e antigen in the maternal serum.
Maternal clinical manifestations¹¹
- May be asymptomatic
- Nausea, anorexia, abdominal pain or discomfort, fatigue, myalgia, dark urine, jaundice
- Chronic hepatitis infection may lead to: ascites, coagulopathy, thrombocytopaenia, oesophageal varices,
Foetal/neonatal clinical manifestations¹²
- Usually asymptomatic
- Jaundice, lethargy, failure to thrive, clay-coloured stools
- Complications: chronic hepatitis, cirrhosis, hepatocellular carcinoma risk
Investigations
- Booking bloods: hepatitis B surface antigen
- If positive in booking bloods
  - LFTs, INR, platelets, complete hepatitis serology, HBV DNA viral load, HIV serology
- At 26-28 weeks
  - Repeat HBV DNA viral load
Management¹⁰
- Dependent on HBV DNA viral load
  - If <200,000 IU/ml → hepatitis B vaccine and hepatitis B immunoglobulin to infant within 12 hours of birth
  - If > 200,000 IU/ml → tenofovir disproxil fumarate for mother, hepatitis vaccine and hepatitis B immunoglobulin to infant within 12 hours of birth
Prevention¹⁰
- Vaccination
- Safe sex practices

Varicella Zoster Virus

Overview¹³:
- Varicella zoster virus (chickenpox) is part of the herpes family. It is highly contagious.
Organism:
- Varicella zoster virus
Transmission¹³
- Respiratory droplets
- Direct contact with fluid from vesicles or indirectly via fomites (clothes, hair, skin cells, bedding)
Maternal clinical manifestations¹³
- Fever
- Malaise
- Pruritic rash: maculopapular → vesicular that crust over
- Severe chickenpox
  - Respiratory symptoms
  - Haemorrhagic rash or bleeding
  - New pocks developing after 6 days of infection
  - Persistent fever >6 days
  - Neurological symptoms
Congenital varicella syndrome clinical manifestations¹⁴
- Skin scarring lesions (cicatrix)
- Limb hypoplasia, atrophy
- Malformed digits
- Ocular defects: chorioretinitis, cataracts, nystagmus
- CNS abnormalities: microcephaly, cortical atrophy, seizures, mental retardation
- Autonomic nervous system dysfunction: neurogenic bladder, hydronephrosis, reflux, oesophageal dilaiton
Investigations
- Serology of antibody status (VZV-IgG)
Management¹⁵
- If significant exposure to VZV (>15 minutes in the same space as someone infected with VZV) → varicella zoster immunoglobulin
- If mother positive in gestation
  - If they present within 24 hours of onset of the rash and >19 weeks gestation → give acyclovir PO 800mg 5x 7 days
  - If > 24 hours: monitor and no aciclovir
  - Severe chickenpox → IV acyclovir 10mg/kg 8 hourly 7-10 days
- For infant
  - If mother had chickenpox 7 days before – 2 days after birth
    - Give high titre varicella zoster immunoglobulin (ZIG) 200 IU IM ideally within 24 hours of birth or within 72 hours or birth
  - If positive in infant
    - <37 weeks at birth: give IV acyclovir
    - 37 weeks or greater: monitor for respiratory symptoms at home or paediatric unit
Prevention
- Vaccination pre-pregnancy

Parvovirus B19¹⁶

Overview: also known as slapped cheek syndrome
Organism: Parvovirus B19
Transmission
- Contact with respiratory secretions
- Hand mouth contact
- Mother → foetus
- Transfusion of blood and blood products
Maternal clinical manifestations
- Erythematous rash “slapped cheek” appearance
- Rubella like rash: maculopapular rash
- Arthralgia or arthritis
- Chronic anaemia in pregnant women who are immunocompromised
Foetal clinical manifestations
- Spontaneous miscarriage, stillbirth
- Hydrops fetalis: Abnormal build-up of fluid in foetal tissues and organs causing oedema. 2-17 weeks after maternal infection
Investigations
- Parvovirus serology
Management
- If both IgG and IgM positive (indicates recent infection):
  - Monitor with serial fetal ultrasound and middle cerebral artery Doppler

Rubella

Overview: congenital rubella syndrome is a condition which affects a foetus whilst in utero in a mother infected by rubella virus. It is the most dangerous if infection occurs in the first 12 weeks of pregnancy.¹⁷
Organism: Rubella virus
Transmission¹⁹
- Droplet spread or direct contact with nasopharyngeal secretions
- Vertical transmission from mother to foetus
- Communicable period: 1 week before to 4 days after the onset of the rash. Most infectious when rash is erupting
Maternal clinical manifestations¹⁹
- Initially, a low grade fever
- Then, maculopapular rash of cephalocaudal spread (head → downwards)
- Post-auricular lymphadenopathy
- Poly-arthritis
- conjunctivitis
- miscarriage
Foetal/neonatal clinical manifestations²⁰
- TRIAD: deafness, cataracts, congenital heart disease
  - Congenital heart disease includes: PDA, pulmonary artery stenosis, ventricular septal defect, atrial septal defect
- Intellectual disability
- Hepatosplenomegaly
- Low birth weight
- “blueberry muffin” rash
- stillbirth
Investigations¹⁷
- Rubella virus IgG and IgM: done at first appointment for all pregnant mothers “booking bloods”
- If requiring prenatal foetal diagnosis: NAAT on amniotic fluid, foetal blood or chorionic villus biopsies
- If requiring post-natal foetal diagnosis: IgG antibodies ELISA for rubella virus
Management¹⁷
- If <18 weeks, may consider counselling on termination of pregnancy
- May try normal human immunoglobulin (NHIG) as post-exposure prophylaxis within 5 days of infection → does not eliminate, but reduces risk of rubella
Prevention
- MMR vaccine at least 4 weeks before pregnancy if never had before

Cytomegalovirus²¹

Overview: CMV is part of the herpes virus family
Organism: cyotmegalovirus
Transmission²²: contact with the saliva, nasal mucous, urine, breast milk, semen and vaginal secretions of those who are infected
Maternal clinical manifestations
- Mostly asymptomatic
- May have fever, lymphadenopathy, sore throat
Foetal/neonatal clinical manifestations
- Petechiae
- Deafness
- Intellectual impairment
- Pneumonitis
- Blindness, chorioretinitis
- Microcephaly
- seizures
Investigations²¹
- Serology: IgG and IgM
- PCR testing on blood, urine, saliva → not first line investigation
- If mother positive, in utero:
  - Foetal ultrasound: foetal ascites, hepatomegaly, IGR, pleural or pericardial effusion, abdominal calcifications, microcephaly, oligo or polyhydramnios, hydrocephalus, intracranial calcifications
  - May need amniocentesis for PCR
- After born:
  - Serology: CMV igM
  - CMV PCR: urine, saliva or blood
  - Ophthalmology review
  - Head ultrasound or MRI: periventricular calcification, ventriculomegaly, cerebral atrophy, white matter abnormalities
Management²¹
- Management may include the following
  - Consult obstetrics/gyane and paeditrician
  - Anti-virals
  - CMV hyperimmune globulin
  - Counselling and consideration of termination of pregnancy
Prevention²²:
- Wash hands thoroughly after contact with young children, changing nappies
- Avoid contact with bodily fluids of young children: e.g., sharing food, drinks, kissing

CMV is the most common congenital viral infection and may be asymptomatic in the mother.

Herpes simplex virus²³

Overview: Neonatal herpes simplex virus infections are rare but can cause significant morbidity and mortality.
Organism: HSV 1 or 2. Primarily HSV2
Transmission
- HSV1: Contact with infected sores, saliva or skin surfaces in or around the mouth
- HSV2: sex through contact with genital or anal surfaces, skin, sores or fluids that are infected
Maternal clinical manifestations
- Usually asymptomatic
- May have vesicular sores in the genital region
Foetal/Neonatal clinical manifestations: occur anywhere between birth and 6 weeks of age
- Fever
- Vesicular rash
- Hypo or hyperpigmentation of skin
- Eye: retinal dysplasia, optic atrophy, chorioretinitis
- Neurological: microcephaly, encephalomalacia, intracranial calcifications
- seizures
- Disseminated infection: features of sepsis, negative cultures, severe liver dysfunction, consumptive coagulopathy within 30 days of life
Investigations
- HSV PCR typing from genital tract of mother
- Post-partum if asymptomatic and high risk of HSV infection
  - Swab of neonates eye, throat, umbilicus and rectum for PCR
  - Urine for PCR
  - FBC
  - LFTs
  - Coagulation profile
- Postpartum if clinical signs of HSV are present
  - Lumbar puncture
Management²⁴
- First and second trimester acquisition of HSV
  - Suppression with anti-virals at 36 weeks:
    - acyclovir 400mg 3x daily until birth, OR
    - valaciclovir 500mg 2x daily until birth
  - vaginal birth should be anticipated
- third trimester acquisition
  - acyclovir 400mg 3x daily until birth, OR
  - valaciclovir 500mg 2x daily until birth
  - Caesarean section should be anticipated. If rupture of membranes occur, delivery should be within 4 hours preferably.
- For the neonate:
  - if asymptomatic and high risk of infection: HSV infection close to birth or baby born through birth canal with active maternal HSV infection, and no previous history of genital HSV
    - Intravenous acyclovir 10 days
  - If symptomatic: intravenous acyclovir
    - If confined to skin, eye and mouth: 14 days
    - For encephalitis or disseminated disease: 21 days
Prevention
- Advising abstinence or use of barrier contraception during pregnancy if one partner has a history of genital herpes

Group B Streptococcus (GBS) infection in pregnancy²⁵

Overview: GBS is a bacteria found in the vagina and bowel in 10-30% of all women. Pregnant women who carry GBS can pass it onto the neonate in the intrapartum period which can cause significant complications in the newborn.
Organism: Group B Streptococcus
Transmission: intrapartum
Risk factors for GBS infection in mother
- Preterm labour
- Rupture of membranes >18 hours prior to birth
- GBS colonisation in current pregnancy
- Previous baby with GBS disease
Maternal clinical manifestations
- Chorioamnionitis
- Urinary tract infection
- endometritis
Foetal clinical manifestations
- Difficulty breathing, tachypnoea, noisy breathing, fever, difficulty feeding, cyanosis, irritability
- Complications: pneumonia, sepsis, meningitis
Investigations
- High vaginal swab for GBS for all women at 25-27 weeks
Management²⁵
- if term premature rupture of membranes (PROM) and:
  - positive: recommend induction of labour (IOL) and intrapartum antibiotic prophylaxis (IAP) (as per below)
  - negative: offer IOL
  - if risk factors for GBS infection: give IAP
- if preterm PROM
  - recommend IAP regardless of GBS status
- intrapartum antibiotic prophylaxis:
  - benzylpenicillin 3g IV as a loading dose at onset of labour
  - benzylpenicillin 1.8g IV every 4 hours until birth
- for neonate
  - if signs of neonatal infection, clinical chorioamnionitis consider IAP
    - benzylpenicillin OR ampicillin/amoxicillin AND gentamicin

Chorioamnionitis²⁶

Overview:
- chorioamnionitis refers to an infection of the placental tissues and amniotic fluid. It can occur antepartum, intrapartum or postpartum.
Organisms: polymicrobial
- Caused by ascending cervicovaginal organisms
  - E.g., GBS, enterobacteria, mycoplasmas
Transmission: ascending infection from the lower genital tract
Maternal clinical manifestations
- Fever (38 or more) and ruptured membranes
- Fever during labour
- Uterine tenderness
- Purulent amniotic fluid
- Complications: PPH due to atony
Foetal clinical manifestations
- Chronic lung disease
- Retinopathy of prematurity
- Very low birth weight
- Impaired brain development: cerebral palsy
Investigations
- Blood cultures if ≥ 38°C
- Low vaginal swab culture
- Mid stream urine culture
- Placenta culture
Management²⁶
- Amoxicillin 2g IV 6 hourly OR Cefazolin 2g IV 8 hourly
- AND gentamicin AND Metronidazole 500mg IV 12 hourly

References

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