Antenatal infections and their consequences

Certain maternal infections can have serious long-term consequences for the fetus whilst others are innocuous. Some may be asymptomatic in pregnancy and go unnoticed.

Infectious diseases in pregnancy screening (IDPS)¹

The IDPS programme currently screens for HIV, hepatitis B and syphilis.

Repeat testing is recommended if individuals:

• Change their sexual partner.

• Inject drugs.

• Are a sex worker.

• Have an infected partner.

• Have a partner who is sexually active with another person.

• Are diagnosed with a sexually transmitted infection (STI).

Viral rash in pregnancy¹

The UK Health Security Agency has produced guidance on the investigation, diagnosis and management of viral illness, or exposure to viral rash illness, in pregnancy. Viral infections which commonly present with a generalised rash illness in the UK include:

• Parvovirus B19.

• Measles.

• Rubella.

• Varicella.

• Human herpes virus 6 and 7 (HHV-6 and HHV-7).

• Enterovirus.

Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and coronavirus (COVID-19) rarely present as a rash illness but should be included as differential diagnoses.

Rubella²

Rubella is a viral infection causing a pink rash, with swelling of lymph glands behind the ears and at the back of the head. There are mild constitutional symptoms and occasionally joint pain in adults.

Consequences

If rubella is contracted within the first 11 weeks of pregnancy there is a 90% chance of the fetus being affected. This falls to 20% during weeks 11-16. In weeks 16-20 there is a slight risk of deafness and, after that, no increased risk.

Fetal defects associated with fetal rubella syndrome include:

• General learning disability.

• Cataracts.

• Deafness.

• Heart defects.

• Intrauterine growth restriction.

• Inflammation of the brain, liver, lungs and bone marrow.

Management³

• With a rubella-like rash, test for rubella and parvovirus B19 (even if reported to be immune); test serum for IgG and IgM and repeat if results are equivocal or as advised by the laboratory. Rising levels suggest recent infection (consult a virologist).

• Evidence of infection should be discussed with the patient with a view to considering termination if indicated and appropriate (consult a fetal medicine specialist).

• Prevention is by measles, mumps and rubella (MMR) vaccine in the second year of life plus a pre-school booster, with antenatal screening for rubella susceptibility. Between 2005 and 2009, 8 out of the 13 reported cases of rubella infection in pregnancy in the UK were in women who were born outside the UK.

Rubella is a notifiable disease in the UK and should be reported to the local Health Protection Unit.

Chickenpox (varicella zoster)

Chickenpox is characterised by fever, malaise and a pruritic rash that develops into crops of maculopapules, which become vesicular and crust over before healing. The incubation period is 7-21 days and the disease is infectious 48 hours before the rash appears, continuing to be infectious until the vesicles crust over (usually within 5-6 days of onset of illness).⁴

More than 90% of the pregnant population are seropositive for varicella IgG antibody, so although contact with chickenpox is common in pregnancy, primary infection is uncommon. It is estimated to complicate 3 in every 1,000 pregnancies.⁵

Consequences

• In adults, chickenpox is associated with greater morbidity - pneumonia (10% of pregnant women), hepatitis and encephalitis.

• It may also cause fetal varicella syndrome (FVS), previously known as congenital varicella syndrome or varicella infection of the newborn.

Before 20 weeks of gestation

• Chickenpox in the first trimester does not increase the risk of spontaneous miscarriage.⁵

• FVS is characterised by one or more of the following:
  

  • Skin scarring in a dermatomal distribution.

  • Microphthalmia, chorioretinitis and cataracts.

  • Hypoplasia of the limbs.

  • Neurological abnormalities - eg, microcephaly, cortical atrophy, intellectual disability, and dysfunction of bowel and bladder sphincters.

• The risk of FVS if a mother develops chickenpox is approximately 0.2% under 13 weeks of gestation, and 2% at 13-20 weeks of gestation.³

20-36 weeks of gestation

• This does not appear to be associated with adverse effects in the fetus.

• It may present as shingles in the first few years of infant life.

After 36 weeks

• Up to 50% of babies are infected and approximately 23% of these develop clinical varicella despite high titres of passively acquired maternal antibody.

• The most severe chickenpox occurs if the infant is born within seven days of onset of the mother's rash.

Management⁴

Of exposure to chickenpox:

• Establish whether the mother is immune. Immunity can be assumed if there is a history of chickenpox or shingles.

• If there is any doubt, request antibody levels urgently (varicella-zoster IgG antibodies).

• Liaise with local microbiology for advice and to expedite results.

• Varicella-zoster immunoglobulin (VZIG) may be indicated.

Of chickenpox in pregnancy:

• Seek specialised obstetric advice urgently about the need for counselling on the risk of fetal complications, antiviral treatment and follow-up.

• VZIG has no place in the management of established infection.

• Monitor the patient closely for complications.

• Admit if any of:

  • Respiratory symptoms.

  • Neurological symptoms other than headache.

  • Haemorrhagic rash or bleeding.

  • Severe disease - eg, dense rash.

  • Significant immunosuppression, including systemic corticosteroids in the previous three months.

Cytomegalovirus⁶

Cytomegalovirus (CMV) is a common viral infection, which is usually mild or asymptomatic in healthy individuals. It may cause a febrile illness or have complications. Congenital CMV is the most common congenitally acquired infection in infants. It is the leading infectious cause of congenital malformation and non-genetic sensorineural hearing loss in children. CMV can be transmitted via breast-feeding, close contact, sexual activity, blood transfusion and organ transplantation. Risk factors associated with CMV infection include having young children, especially if they are in daycare, and working with young children.⁷

In seronegative pregnant women, seroconversion, representing a primary infection, occurs in 1-2% per year. The risk of transmission to the fetus is approximately 32.4% during a primary infection compared with 1.4% in re-activation or re-infection with CMV.

Consequences⁸

• CMV is estimated to affect 1,800 births per year in England and Wales.

• There is a 30-40% risk of intrauterine transmission, and a 20-25% risk of postnatal sequelae if the fetus has been infected. Because there is a good chance the baby will be unharmed, termination is not usually advised.

• The diagnosis can be made antenatally by amniocentesis at least seven weeks after infection and after 21 weeks of gestation. If infection is confirmed, ultrasound is performed regularly to monitor for complications.

• The effect on the fetus is more severe from a primary infection.

• Effects on the fetus or neonate include:
  

  • Intrauterine growth restriction and low birth weight.

  • Hepatosplenomegaly.

  • Jaundice.

  • Thrombocytopenia.

  • Anaemia.

  • Hydrops and ascites.

  • Petechiae and/or purpura.

  • Microcephaly.

  • Intracranial calcifications.

  • Choroidoretinitis.

  • Deafness.

  • Speech defects.

  • General learning disability, which may appear later.

  • Psychomotor delay.

  • Visual impairment.

• At birth, babies may appear normal but hearing defects and intellectual disability may become apparent later in life.

Management

• There is no effective therapy.

• Vaccination is under development.

• IgG antibody testing can confirm primary CMV infection and routine antenatal screening is undertaken in parts of Europe and in Israel.

• Effectiveness of antivirals is awaiting confirmation.

• Prevention is the most important strategy and educating pregnant women on hygiene measures has been shown to reduce seroconversion rates and is recommended. These include:

  • Thorough hand washing after nappy changing, feeding a child or wiping their face or handling children's toys.

  • Not sharing food or utensils with a young child.

  • Avoiding kissing a child on or near the mouth.

Parvovirus B19³

Parvovirus B19 is a common virus with an estimated 50-60% of adults having been infected. Infection with parvovirus B19 has a number of manifestations including:

• Minor febrile illness.

• Erythema infectiosum (slapped cheek disease, fifth disease).

• Generalised rash similar to rubella.

• Arthropathy.

Parvovirus IgM and IgG testing should be done if there is suspicion of exposure or infection. Specialised advice should be sought.

Consequences

• Infection in the first 20 weeks of pregnancy carries an increase of 9% in the risk of intrauterine death, and a 3% risk of hydrops fetalis. Of these, 50% die. Intrauterine transfusion for treatment of fetal anaemia reduces mortality rate.

• These events usually occur 3-5 weeks after the onset of maternal infection.

• Generally the neonate is unaffected. Very rarely, permanent congenital abnormalities and anaemia have been reported.

Management

• On diagnosis, specialised advice should be sought, including the need for serial ultrasound and Doppler assessment; intrauterine transfusion has been shown to improve the outcome of hydrops fetalis.

Measles³

Measles became rare in the UK with the introduction of the MMR vaccine; however, incidence has risen in recent years, due to reduced vaccine uptake following adverse media coverage.

Clinical features include a disseminated maculopapular rash, coryza and conjunctivitis. Complications include pneumonia, otitis media and encephalitis.

Consequences

Measles is uncommon in pregnancy but may be associated with:

• Increased risk of maternal morbidity.

• Intrauterine death or premature labour.

• Rarely, neonatal subacute sclerosing panencephalitis (SSPE).

Management

• If exposure is suspected and there is no history of vaccination or immunity against measles, testing of measles IgG is advised.

• If not detected, human normal immunoglobulin (HNIG) can be given. This may not prevent measles but it may attenuate the illness.

• It is not known if HNIG protects against intrauterine death or preterm delivery.

Toxoplasmosis⁹

Toxoplasmosis is due to infection by the parasite Toxoplasma gondii, with the cat as its definitive host.

Primary infection with toxoplasmosis is often subclinical; however, there may be a nonspecific illness (fatigue, headaches, muscle pains, low-grade fever), or isolated lymphadenopathy. It can be confirmed through serological testing and presence of intrauterine spread tested by amniocentesis.

Consequences

The greatest risk of transmission is in the third trimester; however, consequences are most severe if acquired in the first trimester. There are many different forms of presentation:

• Systemic disease of the neonate:
  

  • Rash.

  • Jaundice.

  • Thrombocytopenic purpura.

  • Hepatosplenomegaly.

  • Pneumonia.

  • Progressive uveitis.

• Neurological disease:
  

  • Hydrocephalus; due to stenosis of the duct of Sylvius requiring shunt.

  • Microcephaly.

  • Microphthalmia.

  • Retinochoroiditis.

  • Cerebral calcification.

• Mild disease: a small area of retinochoroiditis or slight cerebral calcification without signs of brain damage.

• Subclinical.

• Relapsing: retinochoroiditis as flare-ups can occur at any age - most cases in a previously intact retina.

Management

This is by a specialist. Spiramycin throughout pregnancy is used for fetal prophylaxis, with regular ultrasound examination of the fetus. Where infection is confirmed, pyrimethamine, sulfadiazine and folinic acid are used.

Pelvic infection¹⁰

Pelvic inflammatory disease (PID) includes infections of the upper genital tract and is commonly caused by sexually transmitted infections. Chlamydia trachomatis and Neisseria gonorrhoeae have been identified as causative agents but only account for a quarter of cases in the UK. Gardnerella vaginalis, anaerobes and other organisms may be involved.

PID presents with lower abdominal pain and tenderness. It may also present with dyspareunia, abnormal vaginal bleeding and/or discharge. Many cases are asymptomatic.

Consequences

• PID is associated with an increase in preterm delivery, and maternal and fetal morbidity.

• Ophthalmia neonatorum, which is potentially sight-threatening, can also be transmitted.

Management

Pregnant women with PID should be admitted for intravenous (IV) antibiotics, due to increase in both maternal and fetal morbidity:

• None of the evidence-based antibiotic regimens are of proven safety in pregnancy. Benefit may outweigh risk.

• Ceftriaxone has not specifically been studied during pregnancy. However, the risk associated with use of cephalosporins during pregnancy is thought to be low and, although data are limited for individual agents such as ceftriaxone, the cephalosporins as a class are considered to be an appropriate choice during pregnancy.

• Doxycycline is contra-indicated beyond the 15th week of gestation because, from the 16th week of pregnancy, it causes tooth and bone discolouration and inhibits bone growth. However, it can be used in the first trimester. Inadvertent first-trimester use of tetracyclines occurs frequently and has not been associated with an increased risk of congenital malformations.

• Metronidazole has been in clinical use for a long time; experience suggests that it is not teratogenic in humans.

• Ofloxacin has only limited pregnancy-exposure data.

• There are fewer published data on the use of azithromycin rather than erythromycin during pregnancy and breast-feeding. The limited published data do not demonstrate an increased risk of congenital malformations following exposure to azithromycin in human pregnancy.

• Current British Association for Sexual Health and HIV (BASHH) guidelines suggest following local antibiotic policy taking into account local antibiotic sensitivities, but possibly ceftriaxone plus erythromycin +/- metronidazole.

Genital herpes simplex¹¹

Genital herpes simplex produces patches of small, fluid-filled vesicles that burst to form shallow, painful ulcers. Initial infection is followed by recurrences and both occur as self-limiting episodes. All cases in pregnancy should be referred to a genitourinary medicine specialist for advice and testing by viral polymerase chain reaction (PCR).¹²

Consequences

• Herpes simplex virus (HSV) in pregnancy may cause infection in the infant - either:

  • Congenital herpes due to transfer of infection in utero; or

  • Neonatal herpes infection which occurs as a result of infection at the time of birth.

• Congenital herpes is extremely rare. Case reports suggest the skin, eyes and CNS may be affected and there may be fetal growth restriction or fetal death but data are conflicting. HSV acquired in pregnancy is not associated with congenital abnormalities, nor does it increase the risk of miscarriage in the first trimester.

• Neonatal herpes is very rare but serious with high morbidity and mortality:

  • The risk of adverse consequences to the fetus is significantly higher in primary HSV infection than in recurrent infection.

  • The greatest risk of transmission occurs when a new infection is contracted in the third trimester, particularly within six weeks of delivery.

  • Neonatal infection contracted in labour or postnatally may cause eye, skin or mouth lesions, HSV encephalitis, or disseminated HSV with multisystem disease.

  • 70% have disseminated HSV and/or encephalitis and 60% of these infants have no skin, mouth or eye infection.

  • With antiviral treatment, mortality from disseminated disease is 30% and from encephalitis alone it is around 6%. Neurological morbidity is 17% and 70% respectively.

Management

Management depends on whether the genital HSV infection is primary or recurrent and on the gestation of the pregnancy.

• Oral or IV aciclovir should be considered in primary infection in the first or second trimester. Daily suppression with oral aciclovir may be used from 36 weeks of gestation to reduce the chances of lesions being present at delivery and the need for delivery by caesarean.

• Where HSV is contracted during the third trimester, treatment should be continued until delivery. Advise to contact hospital immediately in the event of rupture of membranes or onset of labour. Caesarean section should be recommended, as the risk of HSV transmission is very high (41%). If HSV antibody tests subsequently confirm a recurrent infection, when initially it had been thought to be a primary infection, caesarean may no longer be indicated.

• In recurrent HSV infection, risk of neonatal herpes is low, even if lesions are present at time of delivery (0-3% for vaginal delivery). Aciclovir may not be needed but daily suppression with oral aciclovir may be used from 36 weeks of gestation. Delivery by caesarean section should be offered but the final choice should be made by the woman.

• If a primary episode of genital herpes simplex occurs at the onset of labour, caesarean section should be recommended. If vaginal delivery cannot be prevented, application of fetal scalp electrodes, fetal blood sampling, artificial rupture of membranes and/or instrumental deliveries should all be avoided.

Human immunodeficiency virus¹³

Human immunodeficiency virus (HIV) affects T lymphocytes, macrophages and monocytes with the CD4 receptor. It attacks the immune system, usually over many years, and reduces its effectiveness until an AIDS-defining illness occurs. HIV transmission to the baby is a significant problem, especially in low-income countries. All pregnant women are now screened for HIV.

See also the article on Management of HIV in Pregnancy.

Urinary tract infections¹⁴

Asymptomatic bacteriuria is very common in pregnant women because of the altered dynamics of the urinary tract. If untreated, this frequently progresses to urinary tract infection (UTI) - either acute cystitis (1-2%) and/or pyelonephritis. The symptoms of acute cystitis are the same as in non-pregnant women.

Those of acute pyelonephritis are:

• Pyrexia.

• Rigors.

• Flank pain.

• Nausea and vomiting.

• Headache.

• Frequency and dysuria.

Consequences

UTI increases the risk of pyelonephritis and may increase the incidence of premature labour and low birth weight.

Management¹⁵

• Urine should be screened for asymptomatic bacteriuria by sending urine for culture at the first antenatal visit. If found, a second sample should be sent for culture.

• Both asymptomatic bacteriuria and symptomatic UTI should be treated with antibiotics and a urine sent for culture at every antenatal visit until delivery.

• Refer to local guidelines (and sensitivities if known) for choice of antibiotic. This would usually be amoxicillin, nitrofurantoin, trimethoprim or cefalexin. Use a seven-day course and test for resolution one week after completion of treatment. Manufacturers recommend avoiding trimethoprim in the first trimester because of a theoretical teratogenic risk.¹⁶

• Admission is advised for pregnant women with pyelonephritis, due to the risk of premature labour and maternal renal complications.

• If a group B streptococcus is isolated, inform the antenatal service so that prophylactic antibiotic can be offered during labour.

Influenza¹⁷

Influenza is an acute respiratory illness due to infection with the influenza virus. There are four serotypes - A, B, C and D. Influenza A and B are responsible for most clinical illness and Influenza A is the cause of outbreaks of influenza. The surface antigens of influenza A allow it to be typed further into H and N subtypes.

Consequences

• Influenza during pregnancy may be associated with increased perinatal mortality, prematurity, smaller neonatal size and lower birth weight.¹⁸

• Serious illness from influenza is higher in pregnant women. In the 2009 H1N1 influenza A pandemic, pregnancy was associated with an increased risk of hospitalisation, ICU admission and death.¹⁹

• In the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2017-19, 2 women died from influenza (0.09 per 100,000 maternities). In 2017-19, a total of 191 women died during or up to six weeks after the end of pregnancy.²⁰

Management²¹

• Vaccination is the most effective way of preventing influenza and its complications and will save mothers' and babies' lives.

• Pregnant women should be offered inactivated influenza vaccine (live attenuated influenza vaccine is not recommended)

• Vaccination during pregnancy provides passive immunity to the neonate in the first six months of life.

• Early use of antivirals (withing 48 hours of symptom onset) is indicated if a pregnant woman develops signs of influenza. Hospitalisation may be necessary.