Infections in Pregnancy

Department of Obstetrics and Gynaecology

UWI
 Why are infections in pregnancy important?
• Maternal illness may be worse, as with varicella

• Maternal complications, as with pre-eclampsia

• Preterm labour is also associated with infection

• Vertical transmission of infections can cause miscarriage, can be teratogenic (e.g. rubella) or damage
already developed organs

• Or, as with HIV or hepatitis B, it can cause serious infection in the child

• Neurological damage is more common in the presence of bacterial infection in both preterm and term
babies

• Antibiotic usage in pregnancy is occasionally limited by adverse effects to the fetus.

Cytomegalovirus (CMV)
• Pathology/epidemiology:
CMV is a herpesvirus that is transmitted by personal contact. Up to 1% of women develop CMV infection, usually
subclinical, in pregnancy CMV is a common cause of childhood handicap and deafness.
• Fetal/neonatal effects:
Vertical transmission to the fetus occurs in 40%. Approximately 10% of infected neonates are symptomatic at
birth, with IUGR, pneumonia and thrombocytopenia; most of these will develop severe neurological sequelae such
as hearing, visual and mental impairment, or will die. The asymptomatic neonates are at risk (15%) of deafness.
• Diagnosis:
Ultrasound abnormalities such as intracranial or hepatic calcification are evident in only 20%, and most infections
are diagnosed when CMV testing is specifically requested
If maternal infection is confirmed, amniocentesis at least 6 weeks after maternal infection will confirm or refute
vertical transmission.
• Management:
Most infected neonates are still not seriously affected; close surveillance for ultrasound abnormalities may help
determine those at most risk for severe sequelae. There is no prenatal treatment, and termination may be offered.
Because most maternal infections do not result in neonatal sequelae and amniocentesis involves risk, routine
screening is not advised.
Vaccination is not available
Herpes Simplex
• Pathology/epidemiology:
The type 2 DNA virus is responsible for most genital herpes. Less than 5% of pregnant women have a history of
prior infection, but many more have antibodies.

• Fetal/neonatal effects:
Herpes simplex is not teratogenic. Neonatal infection is rare, but has a high mortality. Vertical transmission occurs
at vaginal delivery, particularly if vesicles are present. This is most likely to follow recent primary maternal
infection (risk 40%), because the fetus will not have passive immunity from maternal antibodies.

• Diagnosis:
This is usually clear clinically and swabs are of little use in pregnancy.

• Management:
Referral to a genitourinary clinic is indicated.
Caesarean section is recommended for those delivering within 6 weeks of a primary attack, and for those with
genital lesions from primary infection at the time of delivery. Daily acyclovir in late pregnancy may reduce the
frequency of recurrences at term. Exposed neonates are given acyclovir. Screening is of little benefit.
Herpes Zoster
• Pathology/epidemiology:
Primary infection with this DNA herpesvirus causes chickenpox, a common childhood illness; reactivation of
latent infection is shingles, which usually affects adults in one or two dermatomes.
A woman who is not immune to zoster can develop chickenpox after exposure to chickenpox or shingles.
Chickenpox in pregnancy is rare (0.03%), but can cause severe maternal illness.

• Fetal/neonatal effects:
Teratogenicity is a rare (1–2%) consequence of early pregnancy infection, which is immediately treated with oral
acyclovir. Maternal infection in the 4 weeks preceding delivery can cause severe neonatal infection; this is most
common (up to 50%) if delivery occurs within 5 days after or 2 days before maternal symptoms.

• Management:
Immunoglobulin is used to prevent, and acyclovir to treat infection. Therefore, pregnant women exposed to
zoster are tested for immunity; immunoglobulin is recommended within 10 days if they are non-immune, and
acyclovir if infection occurs.
In late pregnancy, neonates delivered 5 days after or 2 days before maternal infection are given immunoglobulin,
closely monitored and given acyclovir if infection occurs. Vaccination is possible but not universal.
Rubella
• Pathology/epidemiology:
The rubella virus usually affects children and causes a mild febrile illness with a macular rash,
which is often called ‘German measles’.
Congenital rubella is rare because of widespread immunization and immunity is lifelong.

• Fetal/neonatal effects:
Maternal infection in early pregnancy frequently causes multiple fetal abnormalities, including
deafness, cardiac disease, eye problems and mental retardation.
The probability and severity of malformation decrease with advancing gestation: at 9 weeks the
risk is 90%; after 16 weeks, the risk is very low

• Management/screening:
If a non-immune woman develops rubella before 16 weeks’ gestation, termination of pregnancy
is offered. Screening remains routine at booking to identify those in need of vaccination after
the end of pregnancy. Rubella vaccine is live and contraindicated in pregnancy
Parvovirus
• Epidemiology:
The B19 virus infects 0.25% of pregnant women, and more during epidemics; 50% of women are immune. A ‘slapped cheek’
appearance (erythema infectiosum) is classic but many have arthralgia or are asymptomatic. Infection is usually from children.

• Neonatal/fetal effects:
The virus suppresses fetal erythropoiesis causing anaemia. Variable degrees of thrombocytopenia also occur. Fetal death occurs
in about 10% of pregnancies, usually with infection before 20 weeks’ gestation.

• Diagnosis:
Where maternal exposure or symptoms have occurred, positive maternal IgM testing will prompt fetal surveillance. Anaemia is
detectable on ultrasound, initially as increased blood flow velocity in the fetal middle cerebral artery and subsequently as
oedema (fetal hydrops) from cardiac failure. Or maternal testing may follow the identification of fetal hydrops.
Spontaneous resolution of anaemia and hydrops occurs in about 50%.

• Management:
Mothers infected are scanned regularly to look for anaemia. Where hydrops is detected, in utero transfusion is given if this is
severe. Survivors have an excellent prognosis although very severe disease has been associated with neurological damage
Hepatitis B
• Pathology/epidemiology:
This is caused by a small DNA virus, transmitted by blood products or sexual activity. Infection resolves in
90% of adults, but in 10% persistent infection occurs. This infectious state is present in 1% of pregnant
women in the West but in up to 25% of women from Asia and Africa.
The degree of infectivity depends on antibody status: individuals with the ‘surface’ antibody (HBsAb positive)
are immunologically cured and of low infectivity to others and their fetus. Those with the surface antigen but
not the antibody (HBsAg positive) and those with the E antigen (HBeAg positive) are more infectious.

• Neonatal effects
Vertical transmission occurs at delivery. Importantly, 90% of infected neonates become chronic carriers,
compared to only 10% of infected adults.

• Management/screening:
Because high-risk groups encompass only 50% of chronic carriers, maternal screening is routine in the UK.
Neonatal immunization reduces the risk of infection by >90% and is given to all positive women.
In addition, women with a high viral load are treated with antiviral agents from 32 weeks, with additional
passive immunization given postnatally to the neonate. Known carriers should be handled with sensitive
precautions to avoid infecting staff.
Hepatitis C
• In the UK, about 0.5% of pregnant women are infected, although worldwide the incidence is 3%, and
30% in HIV-positive women.

• Risk factors are drug abuse and sexual transmission

• Hepatitis C leads to chronic hepatitis in about 80%, but most pregnant women are asymptomatic.

• Vertical transmission of HCV occurs in 3–5% but is higher with higher viral loads and with coexisting
HIV infection.

• Elective caesarean section, avoidance of breast feeding, and administration of immune globulin do not
reduce vertical transmission to the neonate.

• Screening is restricted to high-risk groups, e.g. HIV positive.

HIV
• Epidemiology:
In parts of Africa and Asia, rates of infection are nearly 40%. Heterosexual transmission is now
the most important route with a risk of <1% per episode of sexual intercourse.

• Maternal effects:
Pregnancy does not hasten progression to AIDS.
The incidence of pre-eclampsia is greater in HIV-infected women, and this may be increased by
antiretroviral therapy
Gestational diabetes may also be more common.
• Neonatal/fetal effects:
Stillbirth, pre-eclampsia, growth restriction and prematurity are more common.
Congenital abnormalities are not, and antiretrovirals are not teratogenic.
The most important risk is of vertical transmission. This is mostly beyond 36 weeks, intrapartum or during
breastfeeding.
Transmission is greater with low CD4 counts and high viral load (early and late-stage disease), coexistent
infection, premature delivery and during labour, particularly with ruptured membranes for more than 4
hours.
Twenty-five per cent of HIV infected neonates develop AIDS by 1 year and 40% will develop AIDS by 5 years.

• Management/screening:
Screening in the many countries is universal.
HIV-positive women should be managed in conjunction with a physician and have regular CD4 and viral load
test
Genital tract infections such as chlamydia should be sought. Prophylaxis against Pneumocystis carinii
pneumonia (PCP) is given if the CD4 count is low
Drug toxicity is monitored with liver and renal function, haemoglobin and blood glucose testing.
• Strategies to prevent vertical transmission unfortunately need to differ according to the social and
economical circumstances of the population. This is because of the cost of medication and complications of
obstetric intervention, and the benefits of breastfeeding in an under-resourced population.

• The ‘ideal’ policy is highly active antiretroviral therapy (HAART), which reduces viraemia and maternal
disease progression. This is continued throughout pregnancy and delivery, and the neonate is treated for
the first 6 weeks.
• When women are not receiving pre-pregnancy treatment, therapy is started around 28 weeks
• Caesarean section is recommended if the viral load is above 50 copies/mL, and if there is coexistent
hepatitis C infection.
• Breastfeeding is avoided.
• This ‘best’ strategy reduces vertical transmission to <1%.

• In under-resourced countries, nevirapine, as single doses in labour and to the neonate, greatly reduces
vertical transmission in women delivering vaginally. Amniotomy is deferred. Breastfeeding is still advised
but should be exclusive, limited to 6 months, and with antiviral prophylaxis.
• Vertical transmission still occurs, even in resourced countries, and at 20–30% in developing countries,
largely because of lack of knowledge of HIV status and poor access to healthcare
Influenza
• Pathology/epidemiology
In the US and northern Europe, influenza A H3N2 was predominant in the 2014–15 season; influenza A H1N1 the
previous season. Influenza B strains are also seen.

• Maternal effects:
The pandemic influenza A H1N1 (‘swine flu’) strain particularly affects pregnant women, especially those with
comorbidity including obesity

• Neonatal effects:
There are no known adverse effects.
The benefits include improved maternal, and therefore fetal, safety and postnatal passive immunity.

• Management/immunization:
Where symptoms are present, the diagnosis should be considered, oseltamivir prescribed and admission considered,
particularly where there are respiratory symptoms. Seasonal, yearly vaccination with an inactivated vaccine is
strongly recommended for pregnant women at any gestation, for healthcare workers and for vulnerable groups. The
vaccine must be active against the current strain.
ZIKA
• The ZIKA virus was declared a public health emergency of international concern in 2016, following outbreaks
in multiple countries including northern South America, particularly Brazil, Africa and South Asia

• A likely link with fetal central nervous system (CNS) abnormalities, manifest as intracranial calcification,
ventriculomegaly and microcephaly, has recently been made with maternal infection, largely in the first and
second trimester.

• The ZIKA virus is transmitted by the Aedes mosquito which, in contrast to the malaria vector, is active in the
day and therefore best protected against by repellent rather than nets

• Maternal symptoms are mild and include a rash and fever, but also Guillain–Barré syndrome.

• The virus can be detected by PCR but antibody testing is currently unreliable due to cross-reactivity.

• Pregnant women should be advised not to travel to countries affected by outbreaks. Those returning,
particularly with or following suggestive symptoms, should have fetal assessment for CNS abnormalities.

• As no treatment is currently available, termination can be offered to women with clearly affected fetuses.
Group A Streptococcus
• This is the bacterium traditionally responsible for puerperal sepsis

• Group A streptococcus, or Streptococcus pyogenes, is carried by 5–30% of people; the most common
symptom of infection is a sore throat

• Infection during, as opposed to after, pregnancy is usually from children

• Chorioamnionitis with abdominal pain, diarrhoea and severe sepsis may occur

• The infected fetus often dies in utero and labour will usually then ensue

• Early recognition, cultures and high-dose antibiotics ± intensive care in severe cases are required.
Group B Streptococcus
• Pathology/epidemiology:
The bacterium Streptococcus agalactiae is carried, without symptoms, by about 25% of pregnant women.

• Neonatal effects:
The fetus can be infected, normally during labour after the membranes have ruptured. This is most common
with preterm labours, if labour is prolonged or there is a maternal fever.
It causes severe illness and has a mortality of 6% in term infants and 18% in preterm infants.

• Management/screening:
Vertical transmission can be mostly prevented by high–dose intravenous penicillin throughout labour.
Policies differ in different countries:
In the US universal screening is recommended;
In the UK, currently, it is not. treatment is used merely if risk factors for vertical transmission of GBS are
present, or if GBS is found incidentally
Syphilis
• This sexually transmitted infection due to Treponema pallidum is rare although endemic in
some developing countries

• Active disease in pregnancy usually causes miscarriage, severe congenital disease or stillbirth

• Prompt treatment with benzylpenicillin is safe and will prevent, but not reverse, fetal damage

• Therefore screening tests, such as the Venereal Disease Research Laboratories (VDRL) test,
which are cheap and accurate, are still in routine use

• False positives occur particularly with autoimmune disease and the diagnosis should be
confirmed using Treponema-specific tests.
Toxoplasmosis
• Pathology/epidemiology:
This is due to the protozoan parasite Toxoplasma gondii. It follows contact with cat faeces or soil, or eating infected meat

• Fetal/neonatal effects
Fetal infection follows in about 30%; this is more common as pregnancy progresses, but earlier infection is more likely to result in
severe sequelae.
These include mental handicap, convulsions, spasticities and visual impairment

• Diagnosis:
Ultrasound may show hydrocephalus, but maternal infection is usually diagnosed after maternal testing for IgM is performed
because of exposure or anxiety. False positives and negatives are common.
Vertical transmission is diagnosed or excluded using amniocentesis performed after 20 weeks.

• Management
Health education, for example washing hands after contact with soil or cat litter, reduces the risk of maternal infection.
Spiramycin is started as soon as maternal toxoplasmosis is diagnosed
If vertical transmission is subsequently confirmed, additional combination therapy of pyrimethamine and sulfadiazine with folinic
acid is used, though termination may be requested.
Mycobacterium tuberculosis
• Worldwide TB is very common, and its incidence in many countries is increasing because of
immigration, HIV infection and travel

• Tuberculin testing is safe

• Bacille bilié de Calmette–Guérin (BCG) vaccination is live and contraindicated

• Diagnosis in late pregnancy is associated with prematurity, IUGR

• TB is a significant cause of maternal mortality in the developing world

• Treatment with first-line drugs and additional vitamin B6 is safe in pregnancy, but streptomycin is
contraindicated.
Malaria
• Malaria infection is common in developing countries: in sub-Saharan Africa 8% of infant mortality is attributed
to it

• Maternal complications, including severe anaemia, are more frequent in pregnancy, and IUGR and stillbirth are
more common.

• Congenital malaria complicates 1% of affected pregnancies

• Drug usage is dictated by local sensitivity, but most falciparum malaria is resistant to chloroquine or mefloquine

• Artemisin combination therapy (ACT) is increasingly used and appears safe

• Following the diagnosis, surveillance of growth restriction is required

• Prevention of maternal and neonatal effects involves intermittent preventive treatment (IPT) of two doses at least
a month apart, insecticide-impregnated mosquito nets and appropriate drug treatment.
Listeriosis
• Listeria monocytogenes, a Gram-positive bacillus

• Infection can follow consumption of pâtés, soft cheeses and prepacked meals, and causes a non-
specific febrile illness.

• If bacteraemia occurs in pregnancy (0.01% of women), potentially fatal infection of the fetus may
follow.

• The diagnosis is established from blood cultures.

• Prevention involves the widely publicized avoidance of high-risk foods in pregnancy.

Chlamydia and Gonorrhoea
• Chlamydia trachomatis infection in pregnancy occurs in about 5% of women and Neisseria gonorrhoeae
in 0.1%. Most women are asymptomatic.

• Although best known as causes of pelvic inflammatory disease and subfertility, both have been
associated with preterm labour and with neonatal conjunctivitis.

• Chlamydia is treated with azithromycin or erythromycin; tetracyclines cause fetal tooth discoloration

• Gonorrhoea is treated with cephalosporins as resistance to penicillin is common

• Screening and treatment are worthwhile in developing countries, before termination of pregnancy and
in women with a history of preterm labour

• Treatment may reduce the incidence of preterm birth.

Bacterial vaginosis

• This common overgrowth of normal vaginal lactobacilli by anaerobes such as Gardnerella

vaginalis and Mycoplasma hominis can be asymptomatic or cause an offensive vaginal
discharge in women

• Preterm labour and late miscarriage are more common

• Screening and treatment (best with oral clindamycin) reduce the risk of preterm birth if used
before 20 weeks in women with a history of preterm birth.