Oxford Handbook of Obstetrics and Gynaecology (3 edn)
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Rubella (German measles)
Epidemiology
RNA togavirus.
Spread by respiratory droplets—person to person (highly infectious).
Incubation 14–21 days.
Infectious for 7 days before and after appearance of rash.
Re-infection can occur mostly with vaccine-induced immunity.
Symptoms
Mild, febrile illness.
Maculopapular rash.
Arthralgia.
Lymphadenopathy.
Symptoms only present in 50–75% of cases.
Diagnosis
Requires serological confirmation with paired samples; acute and convalescent phase (10–14 days later). Diagnosis is based on:
Appearance of IgM antibodies.
≥4-fold ↑ in IgG antibody titres or increasing IgG avidity.
The virus disrupts mitosis, retarding cellular division and causing vascular damage. Major malformations are most likely during organogenesis with severity decreasing with advancing gestation (Table 4.1). Defects include:
Sensorineural deafness.
Cardiac abnormalities including VSD and patent ductus arteriosus (PDA).
Eye lesions (congenital cataracts, microphthalmia, and glaucoma).
Microcephaly and mental retardation.
Gestation | Risk of transmission | Risk of congenital abnormality | Treatment |
<13wks | 80% | Almost all infected fetuses | TOP may be offered without invasive prenatal diagnosis |
13–16wks | 50% | About 35% of those infected (mainly deafness) | Fetal blood sampling may be later offered to confirm infection |
>16wks | 25% | Rarely causes defects | Reassurance |
Gestation | Risk of transmission | Risk of congenital abnormality | Treatment |
<13wks | 80% | Almost all infected fetuses | TOP may be offered without invasive prenatal diagnosis |
13–16wks | 50% | About 35% of those infected (mainly deafness) | Fetal blood sampling may be later offered to confirm infection |
>16wks | 25% | Rarely causes defects | Reassurance |
Late-developing sequelae include:
Diabetes.
Thyroid disorders.
Progressive panencephalitis.
Prevention
‘Herd immunity’ is maintained by widespread childhood vaccination, although the recent concern over the safety of the mumps, measles, and rubella (MMR) vaccine has decreased the uptake in the UK. Ideally, women should be tested before pregnancy to ensure immunity, but routine screening at booking identifies those at risk and in need of postnatal vaccination.
The vaccine is a live attenuated virus and therefore contraindicated in pregnancy. Women are counselled to avoid pregnancy for 10–12wks after vaccination although there is little evidence of association with congenital infection.
▶ Rapidly confirm rubella in the contact. (This can be readily achieved through notification to the local Health Protection Unit (HPU)).
Reassure if the woman has had:
2 documented doses of rubella vaccine.
1 documented dose of vaccine followed by at least 1 test that has detected rubella antibody≥10IU/mL.
At least 2 previous rubella screening tests that have detected antibody, in at least one of which rubella antibody is≥10IU/mL.
However, she must be advised to return if she develops a rash.
If these criteria are not met, test for IgM and IgG.
▶ Rubella IgG is detected and IgM is NOT detected:
Reassure.
Advise to return if she develops a rash.
▶ Rubella IgM is detected (irrespective of IgG result):
Obtain further serum for IgG and IgM plus avidity.
Reference testing is recommended.
Diagnose and advise on results.
▶ Neither Rubella IgG nor IgM is detected.
Send further sample 1mth after contact or if illness develops.
Diagnose and advise on the results of the second sample.
Immunize with the MMR vaccine after delivery.
Further reading
Health Protection Agency. (2011). Guidance on viral rash in pregnancy. 
http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1294740918985
Measles
Indigenous measles was rare in the UK after the introduction of the MMR vaccine in 1988. Unfortunately, measles has seen an increase recently due to decreased uptake of routine vaccination. 2012 saw 2030 cases in England and Wales, the largest number of reported measles cases since records began in 1995.
Epidemiology
RNA paramyxovirus.
Spread by respiratory droplets—person to person (highly infectious).
Incubation 9–12 days.
Infectious for 2–5 days before and after appearance of rash.
Symptoms
Significant fever.
Generalized maculopapular erythematous rash (appears 2–4 days after onset of symptoms).
Koplik’s spots seen inside the mouth (pathognomonic).
The four C’s: cough, coryza, conjunctivitis and (‘C’) Koplik’s spots.
Maternal complications
Pneumonia.
Acute encephalitis (rarely subacute sclerosing panencephalitis).
Corneal ulceration leading to corneal scarring.
Measles in pregnancy can be associated with maternal mortality, as well as severe morbidity.
Diagnosis
Requires serological confirmation with paired samples; acute and convalescent phase (10–14 days later). Diagnosis is based on:
IgM in serum taken >4 days but <1mth after the onset of rash.
Viral RNA detected in the saliva.
Although associated with fetal loss and preterm delivery, no congenital infection or damage would be anticipated in a surviving fetus.
Neonatal measles has been associated with subacute sclerosing panencephalitis. Therefore, administration of human normal immunoglobulin (HNIG) immediately after birth or exposure is recommended for neonates born to mothers in whom the rash appears 6 days before to 6 days after birth.
▶ Try to rapidly confirm measles in the contact. (This can be readily achieved through notification to the local HPV.)
Factors↑likelihood of the contact having measles include:
The contact took place when the woman was abroad.
The contact with suspected measles had travelled abroad.
The contact had not been vaccinated against measles.
The contact has recently been hospitalized.
Reassure measles risk is remote if the woman has had:
2 documented doses of measles vaccine or
A previous test demonstrating immunity.
However, she must be advised to return if she develops a rash.
If these criteria are not met then send serum for IgG.
Measles IgG detected—reassure.
Measles IgG not detected—arrange HNIG through the local HPU.
▶▶ Women found to be IgG −ve should be immunized with 2 doses of the MMR vaccine after delivery.
Further reading
Health Protection Agency. (2011). Guidance on viral rash in pregnancy. http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1294740918985
Parvovirus B19
Epidemiology
DNA virus.
Spread by respiratory droplets—person to person.
Incubation 4–20 days.
Seroprevalence: ~50% of UK women immune.
Incidence of primary infection in pregnancy <1:100.
Symptoms
Often asymptomatic.
Typical ‘slapped cheek’ rash (erythema infectiosum).
Maculopapular rash.
Fever.
Arthralgia.
Diagnosis
Requires serological confirmation with paired samples; acute and convalescent phase (>10 days later). Recent infection is confirmed by:
Appearance of IgM antibodies.
↑ IgG antibodies.
Maternal risks
Minimal in fit and healthy women. However, immunocompromised individuals are at risk of sudden haemolysis potentially severe enough to require blood transfusion.
Fetal infection rate is thought to be ~30%.
The virus causes suppression of erythropoiesis sometimes with thrombocytopenia and direct cardiac toxicity, eventually resulting in cardiac failure and hydrops fetalis.
There are no congenital defects associated with parvovirus infection.
About 10% of fetuses infected at <20wks gestation will die.
Management
Serial USS, measuring the peak systolic velocity of the fetal middle cerebral artery, are required to monitor for anaemia as this may develop many weeks after the initial infection. In utero red blood cell transfusion should be considered to prevent fetal demise in severely anaemic, hydropic fetuses. These patients should be cared for in a specialist fetal medicine unit.
▶ Many of these fetuses will also be significantly thrombocytopenic and, therefore, a platelet transfusion must be considered to reduce the risk of fetal bleeding at the time of the in utero transfusion.
Send serum for parvovirus B19 IgM and IgG.
▶ Parvovirus B19 IgG is detected and IgM isnotdetected:
Reassure.
Advise to return if mother develops a rash.
▶ Parvovirus B19 IgM is detected (irrespective of IgG result):
Send the sample for confirmatory testing.
Obtain further serum (reference testing is recommended).
Refer for specialist advice.
▶ Neither parvovirus B19 IgG nor IgM is detected:
Send further sample 1mth after contact or if illness develops.
Diagnose and advise on the results of the second sample.
Refer for specialist advice.
Further reading
Health Protection Agency. (2011). Guidance on viral rash in pregnancy. http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1294740918985
Cytomegalovirus
Epidemiology
Herpes virus.
Transmitted in bodily fluids—low infectivity.
Can remain dormant within host for life; reactivation common.
Seroprevalence: ~50% of UK women.
Incidence of 1° infection in pregnancy ~1:100.
Symptoms
Asymptomatic in 95% of cases. May present with:
Fever.
Malaise.
Lymphadenopathy, atypical lymphocytosis, and mononucleosis.
Diagnosis
Maternal infection
Usually requires serological confirmation with paired samples; acute and convalescent phase (14 days later). Recent infection confirmed by:
Significant ↑ in IgM antibodies (may persist for up to 8mths).
↑ IgG antibody titres.
Culture/PCR of maternal urine (not widely available).
Fetal infection
Culture/PCR of amniotic fluid (after 20wks).
IUGR.
Microcephaly.
Hepatosplenamegaly and thrombocytopenia.
Jaundice.
Chorioretinitis.
Later-developing sequelae include:
psychomotor retardation—reported to account for as much as 10% of mental retardation in children <6yrs old
sensorineural hearing loss.
Outcome
With a primary maternal infection 40% of fetuses will be infected, irrespective of gestation. Of these: 90% are normal at birth, of which 20% will develop late, usually minor sequelae.
10% are symptomatic, of which:
33% will die
67% will have long-term problems.
Management
As most fetuses will be unaffected, counselling about management (including TOP) is very difficult, even in the face of confirmed fetal infection. However, close monitoring of fetal growth and well-being is clearly indicated, with appropriate paediatric follow-up.
Investigation will be directed by clinical features and epidemiological information. Causes may include:
Streptococcal infection.
Meningococcal infection.
Enteroviruses.
CMV.
Epstein–Barr virus (EBV).
Syphilis.
Special consideration must be given to the possibility of:
Rubella.
Measles.
Parvovirus B19.
▶ If features are compatible with rubella, measles, or parvovirus B19 appropriate laboratory investigation must be initiated irrespective of past testing or immunization.
▶ Rubella and measles diagnosed on the basis of clinical suspicion are notifiable diseases and should be reported to the local HPU.
Further reading
Health Protection Agency. (2011). Guidance on viral rash in pregnancy. http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1294740918985
Varicella (chickenpox)
Epidemiology
Varicella zoster virus (VZV)—DNA virus.
Spread by respiratory droplets and contact with vesicle fluid.
Incubation 10–21 days.
Infectious from 2 days before rash until all vesicles are crusted.
Seroprevalence: ~90% of UK women immune.
Incidence of 1° infection in pregnancy ~3:1000.
Symptoms
Fever.
Malaise.
Maculopapular rash which becomes vesicular then crusts over.
Diagnosis
If there has been exposure without a good history of previous infection, serum should be tested for VZV IgG antibodies. If antibodies are detected within 10 days of contact, immunity can be assumed and reassurance given. If not, varicella-zoster immunoglobulin (VZIG) should be given as soon as possible. Diagnosis of varicella itself is usually made on the history of contact and appearance of the typical rash.
Varicella in pregnancy is often more severe and may be life-threatening as a consequence of:
Varicella pneumonia.
Hepatitis.
Encephalitis.
Fetal risks
Fetal infection rate is thought to be ~25% in all trimesters: if <20wks there is a 2% risk of fetal varicella syndrome with congenital defects (Table 4.2) including:
Skin scarring.
Limb hypoplasia.
Eye lesions (congenital cataracts, microphthalmia, chorioretinitis).
Neurological abnormalities (mental retardation, microcephaly, cortical atrophy, and dysfunction of bladder and bowel sphincters).
Gestation | Risk to fetus | Management |
<20wks | 2% will develop fetal varicella syndrome (FVS) | Detailed ultrasound examination at 16–20wks, may consider TOP if evidence of FVS seen. Neonatal ophthalmic examination |
>20wks | Not associated with congenital abnormality | Fetal and neonatal surveillance |
Within 4wks of delivery | About 20% will develop neonatal varicella infection | VZIG as soon as possible, 14 days monitoring for signs of infection, and aciclovir if varicella develops |
Gestation | Risk to fetus | Management |
<20wks | 2% will develop fetal varicella syndrome (FVS) | Detailed ultrasound examination at 16–20wks, may consider TOP if evidence of FVS seen. Neonatal ophthalmic examination |
>20wks | Not associated with congenital abnormality | Fetal and neonatal surveillance |
Within 4wks of delivery | About 20% will develop neonatal varicella infection | VZIG as soon as possible, 14 days monitoring for signs of infection, and aciclovir if varicella develops |
Neonatal risks
▶ Neonatal varicella is seen in babies whose mothers contracted it in the last 4wks of pregnancy. Severe infection, which may be fatal, is most likely to occur if the rash appears 5 days before delivery or 2 days after. These babies should all receive VZIG as soon as possible.
Treatment
Oral aciclovir reduces the duration of symptoms if given within 24h of the rash appearing. Its effect on the incidence of serious sequelae is unknown.
Herpes simplex
Epidemiology
Herpes simplex virus (HSV)—type 2 causes >70% genital infections.
Spread by sexual contact.
Incubation ~2–7 days.
Individual may be infectious even when apparently asymptomatic.
Seroprevalence of HSV 2: ~20% of UK women.
Symptoms
Primary HSV infection is the most severe and usually results in:
Mild flu-like illness.
Inguinal lymphadenopathy.
Vulvitis; pain sometimes severe enough to cause urinary retention.
Small, characteristic vesicles on the vulva.
Diagnosis
Usually made on the history appearance of the typical rash, but viral culture of vesicle fluid is the gold standard. Acute and convalescent antibody levels may sometimes be helpful.
Maternal risks
In pregnancy a primary attack may be severe. Complications include:
Meningitis.
Sacral radiculopathy—causing urinary retention and constipation.
Transverse myelitis.
Disseminated infection.
Fetal risks
Primary infection may lead to miscarriage or preterm labour, but no related congenital defects have been identified.
Transmission rate from vaginal delivery during1°maternal infection may be as high as 50%, but is relatively uncommon during a recurrent attack (<5%). Neonatal herpes appears during the first 2wks of life.
25% limited to eyes and mouth only.
75% widely disseminated, of which:
770% will die
many of the survivors will have long-term problems including mental retardation.
Management
Aciclovir may decrease severity and duration of the primary attack if given within 5 days of onset of symptoms. If labour is within 6wks of primary infection then delivery by CS is recommended provided the membranes have not been ruptured for >4h. With active vesicles from a recurrent attack, the risk of surgery must be carefully weighed against the very small risk of neonatal infection.
Malaria
Epidemiology
Protozoan infection (75% Plasmodium falciparum).
Not endemic in the UK, but commonly imported (1378 cases in 2012).
Spread by the bite of a sporozite-bearing female mosquito.
Symptoms
There are often no specific symptoms or signs, with the infection presenting with a ‘flu-like’ illness, but may include:
Fever (cyclical ‘spiking’).
Rigors/chills/sweats.
Muscle pain and general malaise.
Diagnosis
Diagnosis is made from blood films.
Rapid detection tests may miss low parasitaemia.
3 −ve malaria smears 12–24h apart rules out malaria.
Maternal risks
Pregnancy increases the risk of developing severe disease.
Fetal risks
Effects on pregnancy
Miscarriage or preterm delivery.
Stillbirth.
Congenital malaria.
Low birth weight (2° to prematurity or IUGR).
Management
Malaria in pregnancy should be treated as an emergency.
Women should be admitted to hospital.
Quinine and clindamycin is the treatment of choice for falciparum malaria (IV artesunate should be used for severe cases).
Treat the fever with antipyretics.
Screen for anaemia and treat appropriately.
Uncomplicated malaria is not a reason for induction of labour.
▶ Proguanil and chloroquine are probably the safest drugs for malarial prophylaxis in pregnancy.
▶ In the UK, malaria in pregnancy must be reported to the public health authorities and the Health Protection Agency (www.hpa.org.uk) and slides, plus a blood aliquot, should be sent to the Malaria Reference Laboratory for confirmation, which is performed free of charge.
Further reading
RCOG. Green-top guidelines. www.rcog.org.uk
Toxoplasmosis
Epidemiology
Protozoan parasite Toxoplasma gondii.
Spread by contact with cat faeces and eating undercooked meat.
Incubation <2 days.
Seroprevalence: ~20% of UK women immune.
Incidence of 1° infection in pregnancy ~1:500. Rare in UK.
Symptoms
Asymptomatic in about 80% of cases. May present with:
Fever.
Lymphadenopathy.
Diagnosis
Maternal infection
Requires serological confirmation with paired samples; acute and convalescent phase (>28 days later). Recent infection is confirmed by:
Isolated very high titres of IgM antibodies (may persist up to 1yr).
Concurrent high IgM and IgG antibodies.
4-fold ↑ in IgG antibodies.
Fetal infection
May be diagnosed by the presence of IgM antibodies in amniotic fluid or fetal blood. Amniocentesis is accurate only after 20wks. Although ultrasound signs, such as cerebral ventriculomegaly, can occur, most affected fetuses have a normal scan.
Maternal risks
Minimal in fit and healthy women. However, immunocompromised individuals are at risk of severe disseminated illness with chorioretinitis and encephalitis.
Management
Starting spiramycin on diagnosis of maternal infection may decrease the risk of fetal infection. If vertical transmission occurs combination anti-toxoplasmosis therapy is used. Neonatal follow-up should include an ophthalmic review and cranial radiological studies. It is usually recommended that future pregnancies are delayed until maternal IgM antibodies have been cleared.
Spontaneous miscarriage is common with infection in the first trimester (Table 4.3). Defects associated with primary infection include:
Chorioretinitis.
Microcephaly and hydrocephalus.
Intracranial calcification.
Mental retardation.
Gestation | Risk of transmission | Risk of congenital abnormality in infected fetuses |
<12wks | ~17% | 75% |
12–28wks | ~25% | 25% |
>28wks | 65% | <10% |
Gestation | Risk of transmission | Risk of congenital abnormality in infected fetuses |
<12wks | ~17% | 75% |
12–28wks | ~25% | 25% |
>28wks | 65% | <10% |
Hepatitis B
Epidemiology
Hepatitis B virus (HBV)—DNA virus.
Spread by infected blood, blood products, or sexual contact.
Incubation 2–6mths.
Incidence of carrier status in UK women is ~1:100.
Symptoms
Prodrome of non-specific systemic and gastrointestinal symptoms followed by an episode of jaundice.
Diagnosis
Based on clinical picture and serological detection of:
HB surface antigen (HBsAg) → current infection.
HB E antigen (HBeAg) → active viral replication.
Anti-HBsAg antibodies → indicates immunity from either infection or vaccination.
Maternal risks
In the developed world, hepatitis B infection in pregnancy has a similar course to that seen in the non-pregnant individual:
65% subclinical disease with full recovery.
25% develop acute hepatitis.
10% become chronic carriers.
<0.5% develop fulminant hepatitis, which has a significant mortality rate.
Fetal risks
Severe acute infection may lead to miscarriage or preterm labour, but no related congenital defects have been identified.
Management
▶ In the UK all women should be routinely screened for HBV at booking.
▶ High-risk women (e.g. commercial sex workers and IV drug users) should be counselled and vaccinated before pregnancy.
Babies whose mothers have acute or chronic HBV should receive HBV IgG and HBV vaccination within 24h of delivery. This is thought to be up to 95% effective at preventing neonatal HBV infection.
Transmission usually occurs at delivery, but <5% may be due to transplacental bleedingin utero. Neonatal infection may be fatal, and usually results in chronic carrier status with significant lifelong risks of cirrhosis and hepatocellular carcinoma. The carrier status of the mother at delivery determines the risk of vertical transmission:
HBsAg and HBeAg +ve: ~95% risk.
HbsAg +ve and HBeAg −ve: <15% risk.
Group B streptococcus
Epidemiology
Streptococcus agalactiae.
Common bowel commensal.
Up to 20% women carry it vaginally.
Symptoms
None.
Diagnosis
Culture from a lower vaginal swab (LVS) and perianal swab.
Fetal risks
Associated with preterm prelabour rupture of membranes and preterm delivery.
Management
The RCOG does not recommend routine antennal screening for GBS. However, intrapartum antibiotic prophylaxis should be offered to women with a history of previous neonatal GBS infection. Prophylaxis should also be considered if GBS is discovered incidentally in either the vagina or urine, but there is no benefit to be gained from attempting to eradicate it antenatally. Intrapartum prophylaxis should be considered with the following risk factors:
Prematurity (<37wks).
Prolonged rupture of membranes (>18h).
Pyrexia in labour.
Antibiotics
The recommended prophylaxis in labour is IV benzylpenicillin started as soon as possible after onset of labour and at least 2h before delivery (3g initially then 1.5g every 4h throughout labour). In case of penicillin allergy, IV clindamycin should be used (900mg every 8h).
Further reading
RCOG. Green top guidelines. www.rcog.org.uk
Most frequent cause of early-onset, severe neonatal infection (incidence 1:2000 live births). Up to 70% of babies whose mothers carry group B streptococcus (GBS) will themselves be colonized at delivery, but only 1% of these will develop symptoms of sepsis. Early-onset GBS infection (<4 days from delivery) has about a 20% mortality rate and may present with:
Pneumonia.
Septicaemia.
Meningitis.
Late-onset infection (>7 days) is not associated with maternal GBS carriage.
This carries a mortality rate of about 20%. Of those surviving, 50% will have serious neurological sequelae, such as cortical blindness and deafness.
Group A streptococcus
The Centre for Maternal and Child Enquiries (CMACE) 2006–2008 identified infection as a leading direct cause of maternal death. Many deaths were from group A streptococcal (GAS) disease caught in the community, mirroring the rise in general population.
Epidemiology
Streptococcus pyogenes.
Most common bacterial cause of acute pharyngitis (‘strep throat’).
Up to 30% of population are asymptomatic carriers (skin or throat).
Easily spread—person to person or droplet.
Diseases caused by GAS
Pharyngitis.
Impetigo.
Cellulitis.
Scarlet fever.
Rheumatic fever.
Toxic shock syndrome.
Strep throat is one of the most common bacterial infections of childhood.
All of the mothers who died from GAS either worked with or had young children.
Several mothers had a history of a recent sore throat or had a family member with a sore throat or respiratory infection.
Organism may be transferred from the throat or nose to the perineum via the hands when using the toilet or changing sanitary towels.
Antenatal education should raise awareness of this and the importance of good personal hygiene including washing hands before, as well as after, using the toilet or changing sanitary towels.
GAS sepsis should never be underestimated; onset may be insidious with women appearing deceptively well before suddenly collapsing with little or no warning. Once established there may be rapid deterioration into septic shock, disseminated intravascular coagulation (DIC) and multi-organ failure.
Fetal risks
No congenital infection or damage would be anticipated in a fetus following maternal GAS infection.
Further reading
Cantwell R, Clutton-Brock T, Cooper G. (
Other infections
Relatively rare in UK, but increasing (>24% increase since 2004).
Routinely screened for at booking, but care must be taken when interpreting the results as biological false +ves are common.
The spirochaete can cross the placenta and is associated with preterm delivery, stillbirth, and congenital syphilis defects, including:
8th nerve deafness
Hutchinson’s teeth
saddle nose
sabre shins.
Treatment with penicillin:
<16wks—prevents virtually all congenital infection
>16wks—still effective in most cases.
Rare, affecting about 1:10 000 pregnancies in the UK.
Found in soft cheese, pate, undercooked meat, and shellfish.
Produces gastroenteritis often accompanied by flu-like symptoms.
Crosses the placenta causing amnionitis, and miscarriage or preterm labour.
Neonatal infection may be:
generalized septicaemia
pneumonia
meningitis.
Treatment is with high dose amoxicillin or erythromycin.
Epstein–Barr virus
Infectious mononucleosis is a common presentation of primary EBV.
A generalized maculopapular rash may occur (particularly if ampicillin or a similar antibiotic has been taken).
Primary infection in pregnancy carries no specific risk to the fetus.
Enteroviruses
Includes Coxsackie virus groups A and B, echovirus, and enterovirus 68–71.
Wide range of manifestations, including meningitis, rash, febrile illness, and myocarditis.
No clear causal relationship evident for adverse fetal or neonatal outcome.
▶ Hand, foot, and mouth is caused by an enteroviral infection. Primary infection or contact with it in pregnancy is not known to have any adverse consequences for the fetus.
HIV and pregnancy
Facts
In 2010 in the UK:
an estimated 91 500 people were living with HIV
of those about 22 000 are unaware of their infection
2.1 million HIV tests were performed
half of newly diagnosed adults were late stage at diagnosis
less than 1% of people with HIV died.
Over 1/2 have acquired their infection via heterosexual contact.
Around 35% are of black African ethnicity.
Highly active antiretroviral therapy (HAART) (Table 4.4) has ↑ life expectancy.
By 2010 >98% of all diagnosed women received assisted reproductive technologies (ART) before delivery.
Pregnancy does not alter the course of the infection.
High viral loads (VL) and low CD4 counts indicate the likelihood of mother to child transmission (MTCT) and the need for the mother to receive therapy for her own health.
Among women on combination antiretroviral therapy (cART) with an undectable viral load at delivery, MTCT rate is estimated at 0.1%.
Aggregated data on antiretroviral exposure and congenital malformations are collected in the UK by the Antiretroviral Pregnancy Registry (APR).
Class of drug | Examples | Potential problems |
Nucleoside analogue reverse transcriptase inhibitors (NRTI) | Zidovudine (ZDV, previously AZT) Lamivudine (3TC) Didanosine (ddl) Stavudine (d4T) Abacavir (ABC) Tenofovir Emtricitabine | All generally well tolerated, but reported case of: anaemia, nausea, and vomiting; elevated transaminases and hyperglycaemia. Lactic acidosis is a possibility when d4T and ddl are combined |
Non-nucleoside analogue reverse transcriptase (NNRTI) | Nevirapine (NVP) Delavirdine Efavirenz inhibitors | Greatest experience is with NVP, but although well tolerated there is an association with deranged liver function in women with good CD4 counts. Rash is also reported |
Protease inhibitors (PIs) | Ritinovir Indinavir Nelfinavir Saquinavir | Hyperglycaemia is a risk with new-onset diabetes or exacerbation of existing diabetes Diarrhoea, with nausea, vomiting, and altered taste Altered liver function reported |
HIV-1 Integrase strand transfer inhibitor | Raltegravir | Depression Hyperglycaemia Changes in body fat distribution |
Class of drug | Examples | Potential problems |
Nucleoside analogue reverse transcriptase inhibitors (NRTI) | Zidovudine (ZDV, previously AZT) Lamivudine (3TC) Didanosine (ddl) Stavudine (d4T) Abacavir (ABC) Tenofovir Emtricitabine | All generally well tolerated, but reported case of: anaemia, nausea, and vomiting; elevated transaminases and hyperglycaemia. Lactic acidosis is a possibility when d4T and ddl are combined |
Non-nucleoside analogue reverse transcriptase (NNRTI) | Nevirapine (NVP) Delavirdine Efavirenz inhibitors | Greatest experience is with NVP, but although well tolerated there is an association with deranged liver function in women with good CD4 counts. Rash is also reported |
Protease inhibitors (PIs) | Ritinovir Indinavir Nelfinavir Saquinavir | Hyperglycaemia is a risk with new-onset diabetes or exacerbation of existing diabetes Diarrhoea, with nausea, vomiting, and altered taste Altered liver function reported |
HIV-1 Integrase strand transfer inhibitor | Raltegravir | Depression Hyperglycaemia Changes in body fat distribution |
Prepregnancy counselling
Counselling of couples already known to be discordant with regard to HIV infection is important, as the risk of HIV transmission is estimated to be 0.03–1% for each act of unprotected intercourse.
Where the mother is +ve and the partner −ve, self-insemination with the partner’s sperm is recommended.
Sperm washing is recommended if male is +ve and female −ve.
An alternative is donor insemination if the male partner is +ve.
IVF should take account of the parents’ viral load, CD4 counts, and any AIDS defining illness.
Women conceiving on an effective HAART regimen should continue even if it contains efavirenz or does not contain zidovudine. Exceptions are:
protease inhibitor (PI) monotherapy should be intensified to include one or more agents that cross the placenta
the combination of stavudine and didanosine should not be prescribed in pregnancy.
Routine antenatal screening was introduced in 1999 as part of the antenatal booking investigations. This is an opt-out policy and has increased the rate of HIV diagnosis significantly. This has proved to be one of the major successes in the management of HIV-infected patients as MTCT is now a rare occurrence in the UK.
It is estimated that 30–75% of the partners of HIV +ve mothers are unaware of the diagnosis.
▶ It is important to establish the need for healthcare workers and partners to be aware of the diagnosis early so that an effective care plan can be put in place. This may require establishing a local mechanism to flag notes to indicate that additional information is available on a need-to-know basis should the mother be admitted as an emergency.
▶ Women should be encouraged to have all relevant information recorded in their hand-held notes.
Further reading
APR. (2012). www.apregistry.com
HIV: antenatal care
Social and ethical issues
Antenatal care should be delivered by a multidisciplinary team, the precise composition of which will vary.
As there may be social, housing, or immigration issues, the involvement of social services should be considered.
Other support groups may be required if there are issues with regard to drug addiction.
Testing of other children is recommended.
Failure to engage with the antenatal care plan may require the involvement of legal services to address child protection issues.
▶ Local guidelines may exist for the eligibility for free NHS care; however, it is considered unethical to deny treatment to an HIV +ve mother as this treatment would protect her unborn child and potentially her own health.
Highly active antiretroviral therapy in pregnancy
Women requiring HAART for their own health should commence treatment as soon as possible.
By 2011, there were over 11 000 HIV-exposed uninfected children in the UK, whose mothers took some form of ART in pregnancy.
There is most evidence and experience with zidovudine plus lamivudine, but tenofovir plus emtricitabine or abacavir plus lamivudine are acceptable alternatives.
The 3rd agent in HAART should be nevirapine if the CD4 count is less than 250, or efavirenz, or a boosted PI.
No routine dose alterations are recommended for ART during pregnancy.
Women who do not require treatment for themselves should commence temporary HAART at 14/40 if the baseline VL is >30K (consider starting earlier if VL >100 000).
All women should have commenced HAART by 24wks.
Zidovudine monotherapy can be used in women planning a Caesarean section who have a baseline VL of <10000 and a CD4 of >350.
Special considerations
Integrated screening for trisomy 21 is recommended to reduce the number of women requiring invasive testing.
If not on treatment and an invasive procedure cannot be delayed until viral suppression is achieved, it is recommended that women should commence HAART to include raltegravir and be given a single dose of nevirapine 2–4h prior to the procedure.
Fetal USS should be performed as per national guidelines.
If admitted ‘unwell’, consider complications of ART.
ECV can be performed in women with HIV.
Sexual health screening is recommended at presentation and in the 3rd trimester.
Newly diagnosed HIV +ve pregnant women do not require any additional baseline investigations compared with non-pregnant HIV +ve women, other than those routinely performed in the general antenatal clinic.
HIV sequence analysis should be performed prior to initiation of treatment, except for late-presenting women. Post-short-course treatment sequence is recommended to ensure that mutations are not missed with reversion during the off-treatment period.
Women who either conceive on HAART or do not require HAART for their own health should have a minimum of one CD4 count at baseline and one at delivery.
In women who commence HAART in pregnancy a VL should be performed 2–4wks after commencing HAART, at least once every trimester, at 36wks, and at delivery.
In women commencing HAART in pregnancy LFTs should be performed at initiation of HAART and at each antenatal visit.
In the event that a woman who has either conceived on or initiated HAART has not achieved a plasma VL of <50c/mL at 36wks the following interventions are recommended:
review adherence and concomitant medication
perform genotype if appropriate
consider therapeutic drug monitoring
optimize to best regimen
consider intensification.
www.bhiva.org
HIV: perinatal concerns
Delivery
Vaginal delivery
Untreated women with a CD4 count ≥350 and a viral load of <50 can be treated with zidovudine monotherapy or HAART (including Trizivir®) and can aim for a vaginal delivery.
Vaginal delivery is recommended for women on HAART with an HIV viral load <50 at 36wks.
In women in whom a vaginal delivery has been recommended and labour has commenced, obstetric management should follow the same guidelines as for the uninfected population.
Vaginal birth after Caesarean (VBAC) should be offered to women with a viral load <50.
Caesarean delivery
Delivery by CS is recommended for women taking zidovudine monotherapy, irrespective of plasma viral load at the time of delivery and for women with viral load >400 regardless of ART.
Where the indication for CS is the prevention of MTCT, CS should be undertaken at between 38 and 39wks gestation.
Rupture of membranes (ROM)
In the presence of ROM ≥34wks delivery should take place immediately, by either CS or induction of labour (IOL) according to viral load.
When PPROM occurs at <34wks:
steroids should be administered
virological control should be optimized
there should be multidisciplinary discussion about the timing and mode of delivery.
Intrapartum zidovudine
Intrapartum IV zidovudine (ZDV) infusion is recommended in the following circumstances:
women with a viral load of >10000 who present in labour, or with ruptured membranes, or who are admitted for planned CS
untreated women presenting in labour or with ruptured membranes in whom the current viral load is not known.
Women presenting in labour/with ROM/requiring delivery without a documented HIV result must be recommended to have an HIV diagnostic point of care test (POCT).
A reactive POCT result must be acted upon immediately with initiation of the interventions to prevent MTCT without waiting for formal serological confirmation.
A woman who presents after 28wks should commence HAART without delay.
If the viral load is unknown or >100K, a 3 or 4 drug regimen that includes raltegravir is suggested.
An untreated woman presenting in labour at term should be given a stat dose of nevirapine and commence fixed-dose zidovudine with lamivudine and raltegravir.
It is suggested that intravenous zidovudine be infused for the duration of labour and delivery.
www.bhiva.orgHIV: postnatal concerns
Postnatal management and follow-up
Women requiring therapy for their own health (with a history of an AIDS-defining illness or with a CD4 count <350) should continue HAART after delivery.
ART should be continued in all women who commenced cART for MTCT with a CD4 count of between 350 and 500 during pregnancy who are co-infected with hepatitis B virus (HBV) or hepatitis C virus (HCV).
When stopping NNRTI-based HAART post-partum the NNRTI washout period should be covered by 2wks PI-based therapy.
All mothers and children require long-term follow-up.
Neonatal management
Neonatal post-exposure prophylaxis (PEP) should be commenced within 4h of birth and should continue for at least 4wks.
Zidovudine monotherapy is recommended if:
maternal viral load is <50 HIV RNA copies/mL at 36wks gestation/delivery
mother delivered by CS whilst on zidovudine.
Neonates <72h old should initiate 3-drug therapy immediately if:
their mothers are HIV +ve and untreated
maternal viral load at 36wks gestation/delivery is not <50 HIV RNA copies/mL.
Primary pneumocystis pneumonia (PCP) prophylaxis, with co-trimoxazole, should be initiated from age 4wks in:
all HIV infected infants
infants with an initial +ve molecular diagnostic test result
infants whose mother’s viral load at 36wks was >1000 or unknown (and continued until HIV infection has been excluded).
▶ All cases of HIV in pregnancy (whether diagnosed before or during pregnancy) should be reported to the National Study of HIV in Pregnancy and Childhood at the RCOG even if the pregnancy is not continued to term. Email: [email protected]
Further reading
British HIV Association. (2012). Guidelines for the management of HIV infection in pregnant women. www.bhiva.org
Vaccination and travel
Vaccination
Live attenuated vaccines such as rubella, polio, and MMR are contraindicated in pregnancy.
Passive immunization with specific human immunoglobulin is safe and may provide important protection (e.g. VZIG).
Women who are HbsAg −ve but considered at high risk should be offered HBV vaccination in pregnancy.
Vaccinations for travel should be considered on an individual basis, and the small risk from the vaccine compared with the risk from contracting the disease:
cholera—limited efficacy therefore not recommended
hepatitis A—low risk, but consider HNIG for short periods
meningococcus—safety unknown, consider if high risk
rabies—consider immunoglobulin for post-exposure prophylaxis
tetanus—safe in pregnancy
yellow fever—safety unknown, consider if high risk.
Avoid foodstuffs that may pose a potential risk of infection:
Unwashed fruit and vegetables.
Raw eggs.
Undercooked meat.
Tap water in countries with poor sanitation (beware of ice cubes).
Shellfish in hepatitis A endemic areas.
Appropriate antimalarials should be taken, accompanied by avoidance of exposure to mosquito bites:
Mosquito nets.
Long sleeves and trousers (tucked into socks).
Insect repellents.
Recommend that the woman checks that her travel insurance will cover any health or pregnancy-related problems abroad. They may class pregnancy as a ‘pre-existing condition’ and therefore not cover it.
Most airlines will allow pregnant women to fly up to 36wks gestation:
732wks with multiple pregnancy
at >28wks many will request medical certification of fitness to fly.
The risk of venous thromboembolism (VTE) significantly↑with flights of >8h.
Simple measures should be recommended to↓the risk of VTE:
avoid dehydration (and alcohol!)
take regular short walks around the plane
use graduated compression hosiery.
Consider low dose aspirin.
Women with other risk factors for deep vein thrombosis (DVT) (such as factor V Leiden carriers) may require low molecular weight heparin for flights of 5h or more.
