Infections in Pregnancy

Infections in Pregnancy Max Brinsmead MB BS PhD March 2014

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

Rubella in a Pregnant Woman • Before 12 weeks pregnancy • Miscarriage • Cardiac anomalies • Nerve deafness • Cataracts or retinopathy • Mental retardation • Fetus somewhat safer in the 2nd trimester but… • In the second half of pregnancy • Hepatosplenomegaly • Failure to thrive, osteitis • Diabetes, hypothyroidism and GH deficiency • Progressive panencephalitis = The Congenital Rubella Syndrome

Prevention of Congenital Rubella • Immunise all children at 12 -15m (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

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%)

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 fetal blood sampling for HZV PCR

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

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

Recommendations • 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 >5 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 • Even if the woman says she has never had it before

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%

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 immunosupression

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

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

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

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 • 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

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

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

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

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

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%

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

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 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 • 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 • 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 • 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

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

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

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

Listeriosis • Caused by Listeriamonocytogenes • 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 • Fewer than 10 per 100,000 women • Infection may be asymptomatic • But the following symptoms also occur: • Fever (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 • 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 • 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

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

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”

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

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

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

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

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%

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%

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%

Syphilis in Pregnancy • 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

Treatment of Syphilis • 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

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 but of limited use

Infections in Pregnancy