- Email: [email protected]
Infectious disease and pregnancy
Current Obstetrics & Gynaecology (2002) 12, 125 ^130 c 2002 Elsevier Science Ltd doi:10.1054/cuog.2001.0247 available online at http://www.idealibrary.com on
Infectious disease and pregnancy K. S. Langford Consultant Obstetrician, Fetal Medicine Unit,15th Floor Guy’s Tower, Guy’s Hospital, London SE19RT, UK
KEYWORDS congenital infection; teratogenesis; maternal mortality; prematurity
Summary Infectious disease in pregnancy remains worldwide a major cause of maternal and fetal morbidity and mortality. The majority of maternal deaths due to infection occur in developing countries but deaths are not unknown in the UK. Adverse fetal outcomes associated with infection include spontaneous abortion, stillbirth, congenital abnormality, intrauterine growth restriction, prematurity and neonatal infection.While the majority of infections in pregnancy will cause no lasting harm the potential for serious consequences makes a systematic approach to diagnosis and treatment mandatory. This article discusses the most signi¢cant infections encountered in obstetric practice. c 2002 Elsevier Science Ltd
INTRODUCTION The majority of infections experienced by pregnant women resolve without a¡ecting the fetus or causing significant maternal disease. However, the potential for serious harm to mother and fetus remains. In developed countries, maternal death from infection has become a rare event but this is not the case in the developing world. Fetal infection frequently resolves without sequelae, but in a minority of cases the fetus is a¡ected by persistent infection or congenital abnormality. Infectious disease also contributes to perinatal morbidity and mortality through prematurity.
infection. The CEMD highlighted the need to avoid complacency in maternal infection with a number of key recommendations. These include the need for prompt treatment and referral by GPs and midwives of puerperal women with signs of infection (fever and/or o¡ensive vaginal discharge), obtaining timely bacteriological specimens, including blood cultures, in women who are systemically unwell and the early involvement of a microbiologist in serious cases. Treatment should not be delayed pending the results of investigations in women who are systemically unwell. The report also emphasizes the evidence that maternal infectious morbidity after Caesarean section is reduced by antibiotic prophylaxis.
Maternal infectious disease In general, pregnancy does not alter the incidence or severity of maternal infections although the physiological changes of pregnancy predispose to urinary tract infection, pneumonia and chorioamnionitis. There is also evidence that hepatitis B and E, and varicella zoster (VZV) viral infections and malaria may be more severe.The vast majority of maternal deaths occur in developing countries and around one-quarter of these deaths are due to either puerperal sepsis or septic abortion.
Puerperal sepsis Puerperal sepsis was the leading cause of maternal mortality in the UK until the introduction of antibiotics into clinical practice in the late 1930s. The incidence has now declined rapidly but the Con¢dential Enquiry into Maternal Deaths (CEMD) still recorded10 deaths in1994 ^1996, the majority associated with haemolytic streptococcal Correspondence to: KSL.Tel.: þ44 (0)20 7955 4835; Fax: þ44 (0)20 7955 2625; E-mail: [email protected]
Urinary tract infections The physiological changes of pregnancy predispose to urinary tract infections. Pyelonephritis in pregnancy is associated with preterm labour and thus the neonatal morbidity of prematurity. Pyelonephritis is predisposed by asymptomatic bacteriuria with up to 40% of cases of asymptomatic bacteriuria progressing to pyelonephritis if untreated. The majority of asymptomatic bacteriuria is due to Escherichia coli and treatment should be guided by sensitivities. Antibiotics are given for 2 weeks initially and, since 15% will have a recurrence of bacteriuria, should be followed by surveillance with repeat urine cultures. Pyelonephritis should be managed aggressively with intravenous antibiotics because of the risk of preterm labour.
Malaria Malaria in pregnancy is obviously most common in developing countries. However, with increasing travel and immigration, it is becoming more common in the UK. The e¡ects of malaria in pregnancy on the mother and the
126
fetus depend largely on the woman’s previous exposure to infection and her immune status.Women with no preexisting immunity have a high risk of maternal and perinatal mortality with a 3 times greater risk of dying if they develop severe disease. Thus, malaria in a pregnant woman from a non-endemic area should be regarded as a medical emergency and managed as an in-patient jointly with a physician. In areas with moderate to high transmission rates, adults have a high level of immunity to malaria that is maintained by continual exposure. In pregnancy, this immunity is altered so that pregnant women have higher rates and higher density of parasitaemia. This e¡ect is most marked in a ¢rst pregnancy. The infection is frequently asymptomatic and thus untreated but may lead to severe maternal anaemia. Placental parasitization is common and is associated with intrauterine growth restriction (IUGR). Pregnant women from non-endemic areas and those originally from such areas but now residing elsewhere, should be advised to take antimalarial prophylaxis if travelling to endemic areas. Proguanil and chloroquine are safe in pregnancy and should be combined with avoiding mosquito bites by covering exposed skin, using insect repellent and mosquito nets. Detailed advice can be obtained from the travel clinic at the Hospital for Tropical Disease in London or the Liverpool School of Tropical Medicine.
CURRENT OBSTETRICS & GYNAECOLOGY
of exposure, time of onset of symptoms or history of previous vaccination or infection.Taking a meticulous history from the woman and providing the laboratory with such detail will usually expedite results thus minimizing an anxious time for the mother. In many cases, it is helpful to compare a current sample with the one obtained earlier in pregnancy. It is therefore important to establish as to when the woman had booking bloods taken, as these are often stored in the laboratory for some time and could be made available for comparison. The traditional approach to testing for infection in pregnancy has been to request a TORCH screen (toxoplasma, rubella, cytomegalovirus and herpes simplex). As the range of possible infecting agents is considerably more extensive than this, it is generally more helpful to discuss the clinical scenario with the laboratory so that tests can be directed accordingly. A Public Health Laboratory Service working party has recommended that the use of the acronymTORCH be discontinued. Prenatal diagnostic techniques may be used to establish whether a fetus has been infected. However, it is important to draw a distinction between the fetus being infected and the fetus being damaged by the infection. Virological testing may be used to establish whether infection has occurred, but it cannot con¢rm or exclude that the fetus has been a¡ected. Such investigations are usually carried out in a Fetal Medicine Unit.
Rubella
Infections with predominantly fetal or neonatal e¡ects Infections that a¡ect the fetus and/or neonate are predominantly viral but also include bacterial and protozoal infections. Some infections cause congenital abnormality in the fetus while others do not cause structural abnormality but are associated with neonatal infectious morbidity. It is important to remember that only some cases of maternal infection will result in fetal infection and not all cases of fetal infection will result in the fetus being a¡ected. Investigation of potential fetal infection is complex and requires careful discussion with a microbiologist. Referral to a Fetal Medicine Unit may be required for invasive testing.
Investigation of suspected infection in pregnancy Some important general principles apply to diagnosing infections in pregnancy, particularly those caused by viruses. Many tests used are serological and look for changes in antibody titres and the presence of IgM in order to determine if recent infection has occurred. These tests require skilled interpretation before a report can be issued and this process is aided enormously by good clinical information such as date and type
It has long been established that rubella infection in pregnancy may lead to Congenital Rubella Syndrome. In industrialized countries, vaccination programmes have reduced the proportion of women of childbearing age susceptible to rubella to o2^3%. In developing countries, the proportion of susceptible women remains high at 15^25%. The fetus is at risk of infection during the period of maternal viraemia, which predates the onset of clinical features. Fetal infection occurs in the majority of cases of maternal infection in the ¢rst12 weeks and carries a high risk of fetal death. Congenital anomalies occur in 80 ^ 90% of survivors and these infants have a persistent infection, shedding virus for 6 ^12 months after birth. The range of congenital defects seen includes cardiac anomalies, ocular abnormalities, sensorineural deafness, developmental delay, hepatosplenomegaly and thrombocytopenic purpura. The severity of these anomalies requires that termination of pregnancy be o¡ered as an option to the mother. If maternal infection occurs after the ¢rst trimester, fetal anomalies are less common. Fetal anomalies occur in about 15% of cases of maternal infection between 13 and 16 weeks. The predominant defect in second trimester infection is sensorineural deafness. Fetal infection after the ¢rst trimester is not associated with persistent
INFECTIOUS DISEASE AND PREGNANCY
infection.Congenital defects are very rare with maternal infection after 16 weeks. Infection prior to pregnancy does not carry a risk to the fetus. Prenatal diagnostic techniques are of little value in determining which fetuses may have been a¡ected by rubella; a positive result only indicates that a fetus has been infected, not whether it has been a¡ected and a negative result is not completely reassuring as false negatives have been reported. Possible cases of rubella in pregnant women require prompt investigation to con¢rm or refute the diagnosis. Clinical diagnosis is limited because presentation may be atypical and a similar rash may be caused by other viral infections. Women with a rubella-like illness or exposed to a rubella-like illness should be tested for rising antibody titre and/or rubella-speci¢c IgM which would con¢rm recent infection. Precise details about exposure (date, type of contact), previous vaccination and results of previous screening tests for rubella immunity will help the laboratory in interpreting blood tests and thus expedite results. Maternal reinfection in immune women has been reported but the risk to the fetus is thought to be relatively low (o5%). Finally, it is important to remember that women found to be rubella non-immune during pregnancy should be o¡ered postnatal vaccination.The vaccine used is a live attenuated virus and is contra-indicated in pregnancy, which should also be avoided for 1 month after vaccination. However, in over 500 cases where inadvertent administration in pregnancy has occurred, no congenital abnormalities have been reported and termination of pregnancy is not indicated. It is also a good practice to screen women seeking preconceptual counselling or advice on subfertility for rubella immunity so that vaccination can be carried out before pregnancy.
Cytomegalovirus Cytomegalovirus (CMV) infection of the fetus is the second most common cause of mental retardation after Down’s syndrome. In developing countries, childhood CMV infection is so common that the vast majority of women of childbearing age have already been infected. In contrast, in industrialized countries, only 50 ^ 60% of women of childbearing age have antibodies to CMV. Women particularly at risk of seroconversion in pregnancy include those with young children of their own and those working in daycare nurseries. Reactivation following previous infection is also relatively common in pregnancy. CMV infection of the fetus in utero may occur during a primary maternal infection, reactivation or reinfection with a di¡erent CMV strain. However, the fetus is rarely a¡ected in reactivation or reinfection where the mother is antibody positive before pregnancy. In contrast to rubella, CMV infection can produce sequelae
127
over a wide gestational age range and in practice it is often di⁄cult to establish the timing of an infection during pregnancy because CMV infection in adults is usually subclinical. In primary maternal infection 30 ^ 40% of fetuses are infected. Five to seven per cent of those infected will be symptomatic at birth and present with intrauterine growth restrictions (IUGR), jaundice, hepatosplenomegaly, rash, chorioretinitis, intracranial calci¢cation, encephalitis or microcephaly. There is a mortality rate of up to 20% in this group. A further 10 ^15% will be found to have anomalies on follow up, including developing microcephaly, sensorineural hearing loss and psychomotor delay. If maternal infection is suspected, maternal blood should be sent for serology and wherever possible compared to a sample taken at booking. IgM may persist in the circulation for some months after infection, which may cause uncertainty as to whether infection has actually occurred during or shortly before pregnancy. If a primary maternal infection is con¢rmed in pregnancy, prenatal con¢rmation of fetal infection may be sought. The infected fetus sheds virus in its urine and thus into the amniotic £uid where it may be detected from 21 weeks onwards. PCR of amniotic £uid obtained at amniocentesis can be used to detect viral DNA, con¢rming fetal infection. It should be kept in mind that even if fetal infection were con¢rmed, the majority of fetuses would not be a¡ected in the long term. Serial ultrasound scanning may be undertaken to look for features of CMV (IUGR, intracranial calci¢cation or ventriculomegaly, hydrops) although none of these features are speci¢c for CMV and their absence is not a guarantee that a fetus is una¡ected.
Varicella zoster In industrialized countries, the majority of women of childbearing age (485%) are immune to varicella zoster virus (VZV) although it should be kept in mind that women from developing countries are more likely to be susceptible. Following the primary infection (‘chickenpox’), the virus remains latent in the sensory nerve ganglia and can reactivate to cause the rash of herpes zoster (‘shingles’).The fetus is at risk of infection during maternal viraemia, which does not occur in herpes zoster except in the severely immunocompromised. Exposed women should have blood taken for IgG and if this con¢rms past immunity, they can be reassured that the fetus is not at risk. Fetal varicella syndrome (FVS) occurs overall in 1% of fetuses infected before 20 weeks with the risk being highest between weeks 13 and 20 (2%). The features of FVS are cicatricial skin scarring, eye defects, limb hypoplasia, microcephaly and neurological abnormalities including developmental delay. Features may be detected on ultrasound from 5 weeks after the primary infection
128
but their absence does not exclude embryopathy. Prenatal con¢rmation of fetal infection is not usually undertaken because it does not predict fetal damage. If the mother develops perinatal chickenpox, there is a risk of up to 20 ^30% of the neonate developing it also. Neonatal infection may be severe in this situation, as there will have been no transfer of maternal antibodies to the fetus. Passive immunization of the neonate with VZ IgG after birth is recommended if the mother develops infection from 7 days before to 28 days after birth. If the mother develops chickenpox within 5 days of the planned date of an elective delivery, this should be postponed where possible to allow transfer of maternal antibodies to the fetus that may ameliorate neonatal disease. The paediatricians should be advised of the maternal infection so that appropriate neonatal immunization and surveillance can be undertaken. Maternal VZV can be severe with pneumonia occurring in up to10%. If a non-immune pregnant woman is exposed toVZV, she should be givenVZ immunoglobulin as soon as possible as this is e¡ective up to 10 days after contact. If a rash develops, oral aciclovir commenced within 24 h of onset is e¡ective in ameliorating disease. There is a theoretical risk of teratogenesis in the ¢rst trimester but experience so far has been reassuring. As the risk of pneumonia is signi¢cant, women with pre-existing lung disease, immunocompromise or ¢ndings suggestive of pneumonia should be referred to hospital for treatment with intravenous aciclovir.
Parvovirus B19 Parvovirus infections are common in children and by childbearing age, half of all women are immune in industrialized countries. Infections classically present as erythema infectiosum (‘slapped cheek’ appearance) and a rubella-like rash. However, 30 ^ 40% of infection is subclinical. If the mother is exposed to infection in pregnancy booking bloods should be tested for B19 IgG where possible. If the mother was IgG positive at booking, she can be reassured that her pregnancy is not at risk. If she is negative for IgG current blood samples should be tested for speci¢c IgM which lasts for 8 ^12 weeks after infection and for rising IgG titres which typically occur 2^ 4 weeks after contact. Infection in the fetus can lead to severe anaemia and myocarditis that may result in fetal hydrops and death. Fetal death is most commonly reported in maternal infections occurring between 13 and 20 weeks’ gestation and typically takes place 4 ^ 6 weeks after exposure. Loss rates may be up to 9%. After 20 weeks, the loss rate is around 1% and in many cases is preceded by fetal hydrops, which a¡ects approximately1% of fetuses infected in the second and third trimesters. There is no increase in congenital malformations.
CURRENT OBSTETRICS & GYNAECOLOGY
Where maternal infection is con¢rmed, regular fetal surveillance should be instituted. This usually takes the form of weekly ultrasound scans to look for developing hydrops, which should be continued for 12 weeks after infection. If hydrops occurs, urgent referral to a Fetal Medicine Unit is indicated. Fetal anaemia is amenable to in-utero transfusion that supports the fetus until spontaneous recovery occurs.
Herpes simplex virus Genital herpes may be caused by herpes simplex virus type 1 or 2 (HSV-1 or HSV-2) and tends to be particularly £orid in pregnancy because of the relative immunosuppression of the mother. Primary infection in the ¢rst trimester is associated with an increased risk of early miscarriage but there is no recognized pattern of fetal abnormality in pregnancies that continue. The most important aspect of fetal infection with HSV is infection occurring around the time of birth, which may lead to severe neonatal disease. The fetus may become infected as a result of contact with genital lesions during delivery or by ascending infection after rupture of the membranes. This risk is highest in primary infection since maternal genital lesions contain high concentrations of virus and transmission may be as high as 41%. In the UK, delivery by Caesarean section is recommended in women with primary or recurrent genital lesions at the onset of labour or pre-labour rupture of the membranes to minimize the risk of neonatal infection. However, in the Netherlands, vaginal delivery in women with recurrent lesions has not been shown to increase the incidence of neonatal herpes.
Blood-borne viral hepatitis Hepatitis B virus (HBV) carriage among pregnant women in the UK is in the region of 0.1^ 0.5% although it may be up to 1% in inner city areas re£ecting the higher proportion of women from areas with high endemicity (sub-saharan Africa, the far East and Paci¢c Islands).The infectivity of a carrier is determined by the presence of HBV e antigen (HbeAg) and antibodies to it (HbeAb). Women who are HbeAg positive are highly infectious and 90 ^95% of their infants will be infected and develop prolonged HBV carriage themselves. In contrast, only 5% of infants of women who are HbeAb positive will become carriers. The most common mode of transmission to the fetus is during delivery but in 5% of cases, transplacental infection occurs.Fetal HBV infection is not associated with an increased incidence of congenital malformations. Neonates born to women carrying HBV should receive a full course of vaccinations starting within 24 h of birth. Chronic infection with Hepatitis C virus (HCV) is increasingly being recognized in pregnant women. Five
INFECTIOUS DISEASE AND PREGNANCY
per cent of neonates of infected mothers will become infected and current evidence suggests that this ¢gure is not a¡ected by mode of delivery or by breast-feeding. There is currently no available vaccine.
Human immunode¢ciency virus Human immunode¢ciency virus (HIV) is the organism underlying the acquired immunode¢ciency syndrome (AIDS). Transmission from mother to fetus most commonly occurs during delivery, although transplacental passage may also occur. There is no speci¢c pattern of congenital abnormalities associated with congenital HIV infection but without intervention, around 15^35% of neonates will be found to have acquired infection. E¡ective strategies for reducing passage to the fetus during pregnancy and delivery are now available and every e¡ort should be made to identify women with HIV during the antenatal period so that prophylactic measures can be o¡ered and maternal therapy started. In developed countries, combination antiretroviral therapy is the standard treatment used as it reduces viral load and delays the emergence of viral resistance. This is usually continued during pregnancy and has not so far been associated with signi¢cant teratogenesis. E¡ective single agent prophylactic regimes with zidovudine or nevirapine have also been identi¢ed and may help reduce transmission in countries where combination therapy is prohibitively expensive. Delivery by Caesarean section and avoidance of breast-feeding also contribute to reduced transmission although the size of the reduction in women receiving other therapies remains unclear. Use of these strategies in combination can reduce the transmission rate to o2%.
Toxoplasma The UK prevalence of maternal infection withToxoplasma gondii is low at around 2 per 1000. Fetal infection occurs in the minority of cases of maternal infection but may result in severe congenital defects including hydrocephalus, mental retardation and retinochoroiditis. These may present at birth or become apparent later in life. In a study in a low prevalence, untreated population, similar to that in the UK, overall transmission to the fetus was 19% with 15% of infected fetuses showing congenital abnormalities by 1 year of age. Data from France, where the prevalence of toxoplasma infection is higher than in the UK, indicate that the risk of the fetus becoming infected and the risk of it being a¡ected both depend on the gestation at maternal seroconversion. The risk of infection increases from 2% at 8 weeks to around 75% at term. In contrast, the risk of the neonate manifesting congenital abnormalities in the ¢rst 3 years of life, a situation associated with high risk of long-term impairment, is greater if the earlier infec-
129
tion occurs. It should be noted that this study was carried out in France where mothers are commonly treated with spiramycin after the diagnosis of infection during pregnancy. Treatment with spiramycin from diagnosis of maternal infection onwards may be used to try to reduce the number of cases of congenital abnormalities associated with in utero infection. However, the e⁄cacy of spiramycin has never been tested in a placebo-controlled trial.There are no reports of signi¢cant side e¡ects associated with its use in pregnancy. In cases of proven fetal infection or high risk to the fetus (e.g. maternal seroconversion after 32 weeks), 3-week courses of pyrimethamine (50 mg/ 24 h), sulphadiazine (3 g/24 h) and folinic acid (20 mg/ 24 h) may be given alternating with spiramycin. Interval amniocentesis or fetal blood sampling may con¢rm fetal infection in utero. If infection is con¢rmed, ultrasound surveillance for abnormalities should be undertaken in order to detect the minority of fetuses that have been a¡ected. Ultrasound abnormalities are a late sign and serial scans are needed. The most common abnormality is cerebral ventriculomegaly (78% of fetuses with ultrasound abnormality) with other ¢ndings including intracranial calci¢cation, hepatomegaly and placental thickening or calci¢cation. Unfortunately, a lack of abnormality on USS does not guarantee that an infected fetus will be una¡ected although data on the size of this risk are not clear from the literature.
Syphilis Syphilis is caused by infection with Treponema pallidum. Fetal infection may occur during any stage of maternal infection but is more common (90%) in primary, secondary or early latent maternal infection than in late latent infection (10%). Although infection may occur at any stage of pregnancy, manifestations only occur in the fetus once it mounts an immune response from about 18 weeks of gestation onwards. Approximately 25% of infections end in fetal loss, 25% in preterm labour or intrauterine growth restriction and 50% in a congenitally infected neonate. Fetal infection may manifest on ultrasound as intrauterine growth restriction, hydrops fetalis, polyhydramnios or hepatomegaly. Infection can be con¢rmed by testing of amniotic £uid or fetal blood for Treponema pallidum antigen, although a negative result does not completely exclude infection. If maternal infection is diagnosed during pregnancy, treatment should be undertaken in conjunction with genitourinary medicine specialists so that contact tracing is not neglected. Antibiotic therapy is usually with high-dose penicillin. Erythromycin does not cross the placenta in adequate doses to treat the fetus and tetracycline should be avoided because of its potential e¡ects on bone and dentition. While treatment will cure fetal
130
infection it will not necessarily reverse existing fetal damage.
Listeria Maternal infection with Listeria monocytogenes may occur from ingestion of contaminated foodstu¡s, particularly unpasteurized dairy products, preprepared cook-chill meals, pa“te¤ and raw vegetables. Maternal infection is usually asymptomatic but may present as diarrhoea, in£uenza-like illness or as a febrile illness associated with preterm labour and meconium staining of the amniotic £uid. Con¢rmation of maternal infection may be sought by blood culture in febrile women. In a small but unde¢ned proportion of women with infection during pregnancy, the fetus will become infected during maternal bacteraemia. In early pregnancy, fetal infection may result in miscarriage while in later pregnancy fetal septicaemia may result in damage to multiple organs and stillbirth or neonatal death. It is not known to what extent maternal treatment may ameliorate the fetal effects, but treatment with ampicillin and gentamicin has been advocated.
CURRENT OBSTETRICS & GYNAECOLOGY (ROM), pyrexia 4381C in labour, ROM for 418 h prior to delivery or previous a¡ected child. This results in around 18% of women receiving antibiotics and 69% of cases being prevented although only 50% of mothers of infants with disease have been found to have a risk factor. At present there is no uni¢ed approach to antibiotic prophylaxis in the UK.
CONCLUSION Although the majority of infectious diseases in pregnancy does not result in signi¢cant harm to mother or fetus, the potential for this must not be forgotten. Managing such infections is a complex area, which should involve not only obstetricians but also fetal medicine specialists, microbiologists and physicians.
PRACTICE POINTS K
K
Group B Streptococcus Group B Streptococcus (GBS) is the most common lifethreatening neonatal infection in industrialized countries.GBS is found as a normal commensal in vaginal £ora in 10 ^20% of pregnant women. Around 40 ^70% of the infants of colonized mothers become colonized in the ¢rst week of life while a small number develop acute infection. Infection presents as sepsis, meningitis or pneumonia and is divided into early and late onset disease. Early onset disease is the result of vertical transmission of GBS. Neonatal mortality is around 10%, being signi¢cantly higher in preterm infants. Intrapartum antibiotic administration to high-risk mothers is e¡ective in reducing neonatal infection (penicillin G 3 g intravenously initially then 1.5 g 4 hourly until delivery). High-risk mothers may be identi¢ed by screening or a risk-based strategy. With screening, all women are o¡ered a vaginal swab at 35^37 weeks and those with a positive culture given intrapartum antibiotics. This would result in around 25% of women receiving antibiotics and prevent up to 90% of neonatal cases. With a risk-based strategy antibiotics are given to women in preterm labour, with preterm rupture of membranes
K
Puerperal sepsis remains a cause of maternal death and should be aggressively managed Investigation of infections that can a¡ect the fetus should be undertaken in consultation with a fetal medicine unit Testing for HIV infection should be actively encouraged because e¡ective interventions exist to reduced vertical transmission
FURTHER READING Brocklehurst P. Interventions aimed at decreasing the risk of mother-to-child transmission of HIV infection (Cochrane Review). In: The Cochrane Library, Issue 2. Oxford: Update Software, 2000. Drife J, Lewis G (eds).Why mothers die. Report on Con¢dential Enquiries into Maternal Deaths in the United Kingdom 1994 ^1996. London: The Stationery O⁄ce,1998. MacLean A, Regan L, Carrington D (eds). Infection and Pregnancy. London: RCOG Press, 2001. Nelson-Piercy, C. Handbook of Obstetric Medicine, 2nd edition. London: Martin Dunitz, 2002. Royal College of Obstetricians and Gynaecologists. Chickenpox in Pregnancy.Guideline Number 13, 2001. Sutherland S (ed). Torch screening reassessed: the report of a PHLS working party on diagnostic tests for congenital infections, 2nd edition. London: Public Health Laboratory Service,1993. Zuckerman AJ, Banatvala JE, Pattinson JR (eds). Principles and Practice of Clinical Virology, 4th edition. Chichester; John Wiley and Sons, 2000; 387^ 418.
Infectious disease and pregnancy K. S. Langford Consultant Obstetrician, Fetal Medicine Unit,15th Floor Guy’s Tower, Guy’s Hospital, London SE19RT, UK
KEYWORDS congenital infection; teratogenesis; maternal mortality; prematurity
Summary Infectious disease in pregnancy remains worldwide a major cause of maternal and fetal morbidity and mortality. The majority of maternal deaths due to infection occur in developing countries but deaths are not unknown in the UK. Adverse fetal outcomes associated with infection include spontaneous abortion, stillbirth, congenital abnormality, intrauterine growth restriction, prematurity and neonatal infection.While the majority of infections in pregnancy will cause no lasting harm the potential for serious consequences makes a systematic approach to diagnosis and treatment mandatory. This article discusses the most signi¢cant infections encountered in obstetric practice. c 2002 Elsevier Science Ltd
INTRODUCTION The majority of infections experienced by pregnant women resolve without a¡ecting the fetus or causing significant maternal disease. However, the potential for serious harm to mother and fetus remains. In developed countries, maternal death from infection has become a rare event but this is not the case in the developing world. Fetal infection frequently resolves without sequelae, but in a minority of cases the fetus is a¡ected by persistent infection or congenital abnormality. Infectious disease also contributes to perinatal morbidity and mortality through prematurity.
infection. The CEMD highlighted the need to avoid complacency in maternal infection with a number of key recommendations. These include the need for prompt treatment and referral by GPs and midwives of puerperal women with signs of infection (fever and/or o¡ensive vaginal discharge), obtaining timely bacteriological specimens, including blood cultures, in women who are systemically unwell and the early involvement of a microbiologist in serious cases. Treatment should not be delayed pending the results of investigations in women who are systemically unwell. The report also emphasizes the evidence that maternal infectious morbidity after Caesarean section is reduced by antibiotic prophylaxis.
Maternal infectious disease In general, pregnancy does not alter the incidence or severity of maternal infections although the physiological changes of pregnancy predispose to urinary tract infection, pneumonia and chorioamnionitis. There is also evidence that hepatitis B and E, and varicella zoster (VZV) viral infections and malaria may be more severe.The vast majority of maternal deaths occur in developing countries and around one-quarter of these deaths are due to either puerperal sepsis or septic abortion.
Puerperal sepsis Puerperal sepsis was the leading cause of maternal mortality in the UK until the introduction of antibiotics into clinical practice in the late 1930s. The incidence has now declined rapidly but the Con¢dential Enquiry into Maternal Deaths (CEMD) still recorded10 deaths in1994 ^1996, the majority associated with haemolytic streptococcal Correspondence to: KSL.Tel.: þ44 (0)20 7955 4835; Fax: þ44 (0)20 7955 2625; E-mail: [email protected]
Urinary tract infections The physiological changes of pregnancy predispose to urinary tract infections. Pyelonephritis in pregnancy is associated with preterm labour and thus the neonatal morbidity of prematurity. Pyelonephritis is predisposed by asymptomatic bacteriuria with up to 40% of cases of asymptomatic bacteriuria progressing to pyelonephritis if untreated. The majority of asymptomatic bacteriuria is due to Escherichia coli and treatment should be guided by sensitivities. Antibiotics are given for 2 weeks initially and, since 15% will have a recurrence of bacteriuria, should be followed by surveillance with repeat urine cultures. Pyelonephritis should be managed aggressively with intravenous antibiotics because of the risk of preterm labour.
Malaria Malaria in pregnancy is obviously most common in developing countries. However, with increasing travel and immigration, it is becoming more common in the UK. The e¡ects of malaria in pregnancy on the mother and the
126
fetus depend largely on the woman’s previous exposure to infection and her immune status.Women with no preexisting immunity have a high risk of maternal and perinatal mortality with a 3 times greater risk of dying if they develop severe disease. Thus, malaria in a pregnant woman from a non-endemic area should be regarded as a medical emergency and managed as an in-patient jointly with a physician. In areas with moderate to high transmission rates, adults have a high level of immunity to malaria that is maintained by continual exposure. In pregnancy, this immunity is altered so that pregnant women have higher rates and higher density of parasitaemia. This e¡ect is most marked in a ¢rst pregnancy. The infection is frequently asymptomatic and thus untreated but may lead to severe maternal anaemia. Placental parasitization is common and is associated with intrauterine growth restriction (IUGR). Pregnant women from non-endemic areas and those originally from such areas but now residing elsewhere, should be advised to take antimalarial prophylaxis if travelling to endemic areas. Proguanil and chloroquine are safe in pregnancy and should be combined with avoiding mosquito bites by covering exposed skin, using insect repellent and mosquito nets. Detailed advice can be obtained from the travel clinic at the Hospital for Tropical Disease in London or the Liverpool School of Tropical Medicine.
CURRENT OBSTETRICS & GYNAECOLOGY
of exposure, time of onset of symptoms or history of previous vaccination or infection.Taking a meticulous history from the woman and providing the laboratory with such detail will usually expedite results thus minimizing an anxious time for the mother. In many cases, it is helpful to compare a current sample with the one obtained earlier in pregnancy. It is therefore important to establish as to when the woman had booking bloods taken, as these are often stored in the laboratory for some time and could be made available for comparison. The traditional approach to testing for infection in pregnancy has been to request a TORCH screen (toxoplasma, rubella, cytomegalovirus and herpes simplex). As the range of possible infecting agents is considerably more extensive than this, it is generally more helpful to discuss the clinical scenario with the laboratory so that tests can be directed accordingly. A Public Health Laboratory Service working party has recommended that the use of the acronymTORCH be discontinued. Prenatal diagnostic techniques may be used to establish whether a fetus has been infected. However, it is important to draw a distinction between the fetus being infected and the fetus being damaged by the infection. Virological testing may be used to establish whether infection has occurred, but it cannot con¢rm or exclude that the fetus has been a¡ected. Such investigations are usually carried out in a Fetal Medicine Unit.
Rubella
Infections with predominantly fetal or neonatal e¡ects Infections that a¡ect the fetus and/or neonate are predominantly viral but also include bacterial and protozoal infections. Some infections cause congenital abnormality in the fetus while others do not cause structural abnormality but are associated with neonatal infectious morbidity. It is important to remember that only some cases of maternal infection will result in fetal infection and not all cases of fetal infection will result in the fetus being a¡ected. Investigation of potential fetal infection is complex and requires careful discussion with a microbiologist. Referral to a Fetal Medicine Unit may be required for invasive testing.
Investigation of suspected infection in pregnancy Some important general principles apply to diagnosing infections in pregnancy, particularly those caused by viruses. Many tests used are serological and look for changes in antibody titres and the presence of IgM in order to determine if recent infection has occurred. These tests require skilled interpretation before a report can be issued and this process is aided enormously by good clinical information such as date and type
It has long been established that rubella infection in pregnancy may lead to Congenital Rubella Syndrome. In industrialized countries, vaccination programmes have reduced the proportion of women of childbearing age susceptible to rubella to o2^3%. In developing countries, the proportion of susceptible women remains high at 15^25%. The fetus is at risk of infection during the period of maternal viraemia, which predates the onset of clinical features. Fetal infection occurs in the majority of cases of maternal infection in the ¢rst12 weeks and carries a high risk of fetal death. Congenital anomalies occur in 80 ^ 90% of survivors and these infants have a persistent infection, shedding virus for 6 ^12 months after birth. The range of congenital defects seen includes cardiac anomalies, ocular abnormalities, sensorineural deafness, developmental delay, hepatosplenomegaly and thrombocytopenic purpura. The severity of these anomalies requires that termination of pregnancy be o¡ered as an option to the mother. If maternal infection occurs after the ¢rst trimester, fetal anomalies are less common. Fetal anomalies occur in about 15% of cases of maternal infection between 13 and 16 weeks. The predominant defect in second trimester infection is sensorineural deafness. Fetal infection after the ¢rst trimester is not associated with persistent
INFECTIOUS DISEASE AND PREGNANCY
infection.Congenital defects are very rare with maternal infection after 16 weeks. Infection prior to pregnancy does not carry a risk to the fetus. Prenatal diagnostic techniques are of little value in determining which fetuses may have been a¡ected by rubella; a positive result only indicates that a fetus has been infected, not whether it has been a¡ected and a negative result is not completely reassuring as false negatives have been reported. Possible cases of rubella in pregnant women require prompt investigation to con¢rm or refute the diagnosis. Clinical diagnosis is limited because presentation may be atypical and a similar rash may be caused by other viral infections. Women with a rubella-like illness or exposed to a rubella-like illness should be tested for rising antibody titre and/or rubella-speci¢c IgM which would con¢rm recent infection. Precise details about exposure (date, type of contact), previous vaccination and results of previous screening tests for rubella immunity will help the laboratory in interpreting blood tests and thus expedite results. Maternal reinfection in immune women has been reported but the risk to the fetus is thought to be relatively low (o5%). Finally, it is important to remember that women found to be rubella non-immune during pregnancy should be o¡ered postnatal vaccination.The vaccine used is a live attenuated virus and is contra-indicated in pregnancy, which should also be avoided for 1 month after vaccination. However, in over 500 cases where inadvertent administration in pregnancy has occurred, no congenital abnormalities have been reported and termination of pregnancy is not indicated. It is also a good practice to screen women seeking preconceptual counselling or advice on subfertility for rubella immunity so that vaccination can be carried out before pregnancy.
Cytomegalovirus Cytomegalovirus (CMV) infection of the fetus is the second most common cause of mental retardation after Down’s syndrome. In developing countries, childhood CMV infection is so common that the vast majority of women of childbearing age have already been infected. In contrast, in industrialized countries, only 50 ^ 60% of women of childbearing age have antibodies to CMV. Women particularly at risk of seroconversion in pregnancy include those with young children of their own and those working in daycare nurseries. Reactivation following previous infection is also relatively common in pregnancy. CMV infection of the fetus in utero may occur during a primary maternal infection, reactivation or reinfection with a di¡erent CMV strain. However, the fetus is rarely a¡ected in reactivation or reinfection where the mother is antibody positive before pregnancy. In contrast to rubella, CMV infection can produce sequelae
127
over a wide gestational age range and in practice it is often di⁄cult to establish the timing of an infection during pregnancy because CMV infection in adults is usually subclinical. In primary maternal infection 30 ^ 40% of fetuses are infected. Five to seven per cent of those infected will be symptomatic at birth and present with intrauterine growth restrictions (IUGR), jaundice, hepatosplenomegaly, rash, chorioretinitis, intracranial calci¢cation, encephalitis or microcephaly. There is a mortality rate of up to 20% in this group. A further 10 ^15% will be found to have anomalies on follow up, including developing microcephaly, sensorineural hearing loss and psychomotor delay. If maternal infection is suspected, maternal blood should be sent for serology and wherever possible compared to a sample taken at booking. IgM may persist in the circulation for some months after infection, which may cause uncertainty as to whether infection has actually occurred during or shortly before pregnancy. If a primary maternal infection is con¢rmed in pregnancy, prenatal con¢rmation of fetal infection may be sought. The infected fetus sheds virus in its urine and thus into the amniotic £uid where it may be detected from 21 weeks onwards. PCR of amniotic £uid obtained at amniocentesis can be used to detect viral DNA, con¢rming fetal infection. It should be kept in mind that even if fetal infection were con¢rmed, the majority of fetuses would not be a¡ected in the long term. Serial ultrasound scanning may be undertaken to look for features of CMV (IUGR, intracranial calci¢cation or ventriculomegaly, hydrops) although none of these features are speci¢c for CMV and their absence is not a guarantee that a fetus is una¡ected.
Varicella zoster In industrialized countries, the majority of women of childbearing age (485%) are immune to varicella zoster virus (VZV) although it should be kept in mind that women from developing countries are more likely to be susceptible. Following the primary infection (‘chickenpox’), the virus remains latent in the sensory nerve ganglia and can reactivate to cause the rash of herpes zoster (‘shingles’).The fetus is at risk of infection during maternal viraemia, which does not occur in herpes zoster except in the severely immunocompromised. Exposed women should have blood taken for IgG and if this con¢rms past immunity, they can be reassured that the fetus is not at risk. Fetal varicella syndrome (FVS) occurs overall in 1% of fetuses infected before 20 weeks with the risk being highest between weeks 13 and 20 (2%). The features of FVS are cicatricial skin scarring, eye defects, limb hypoplasia, microcephaly and neurological abnormalities including developmental delay. Features may be detected on ultrasound from 5 weeks after the primary infection
128
but their absence does not exclude embryopathy. Prenatal con¢rmation of fetal infection is not usually undertaken because it does not predict fetal damage. If the mother develops perinatal chickenpox, there is a risk of up to 20 ^30% of the neonate developing it also. Neonatal infection may be severe in this situation, as there will have been no transfer of maternal antibodies to the fetus. Passive immunization of the neonate with VZ IgG after birth is recommended if the mother develops infection from 7 days before to 28 days after birth. If the mother develops chickenpox within 5 days of the planned date of an elective delivery, this should be postponed where possible to allow transfer of maternal antibodies to the fetus that may ameliorate neonatal disease. The paediatricians should be advised of the maternal infection so that appropriate neonatal immunization and surveillance can be undertaken. Maternal VZV can be severe with pneumonia occurring in up to10%. If a non-immune pregnant woman is exposed toVZV, she should be givenVZ immunoglobulin as soon as possible as this is e¡ective up to 10 days after contact. If a rash develops, oral aciclovir commenced within 24 h of onset is e¡ective in ameliorating disease. There is a theoretical risk of teratogenesis in the ¢rst trimester but experience so far has been reassuring. As the risk of pneumonia is signi¢cant, women with pre-existing lung disease, immunocompromise or ¢ndings suggestive of pneumonia should be referred to hospital for treatment with intravenous aciclovir.
Parvovirus B19 Parvovirus infections are common in children and by childbearing age, half of all women are immune in industrialized countries. Infections classically present as erythema infectiosum (‘slapped cheek’ appearance) and a rubella-like rash. However, 30 ^ 40% of infection is subclinical. If the mother is exposed to infection in pregnancy booking bloods should be tested for B19 IgG where possible. If the mother was IgG positive at booking, she can be reassured that her pregnancy is not at risk. If she is negative for IgG current blood samples should be tested for speci¢c IgM which lasts for 8 ^12 weeks after infection and for rising IgG titres which typically occur 2^ 4 weeks after contact. Infection in the fetus can lead to severe anaemia and myocarditis that may result in fetal hydrops and death. Fetal death is most commonly reported in maternal infections occurring between 13 and 20 weeks’ gestation and typically takes place 4 ^ 6 weeks after exposure. Loss rates may be up to 9%. After 20 weeks, the loss rate is around 1% and in many cases is preceded by fetal hydrops, which a¡ects approximately1% of fetuses infected in the second and third trimesters. There is no increase in congenital malformations.
CURRENT OBSTETRICS & GYNAECOLOGY
Where maternal infection is con¢rmed, regular fetal surveillance should be instituted. This usually takes the form of weekly ultrasound scans to look for developing hydrops, which should be continued for 12 weeks after infection. If hydrops occurs, urgent referral to a Fetal Medicine Unit is indicated. Fetal anaemia is amenable to in-utero transfusion that supports the fetus until spontaneous recovery occurs.
Herpes simplex virus Genital herpes may be caused by herpes simplex virus type 1 or 2 (HSV-1 or HSV-2) and tends to be particularly £orid in pregnancy because of the relative immunosuppression of the mother. Primary infection in the ¢rst trimester is associated with an increased risk of early miscarriage but there is no recognized pattern of fetal abnormality in pregnancies that continue. The most important aspect of fetal infection with HSV is infection occurring around the time of birth, which may lead to severe neonatal disease. The fetus may become infected as a result of contact with genital lesions during delivery or by ascending infection after rupture of the membranes. This risk is highest in primary infection since maternal genital lesions contain high concentrations of virus and transmission may be as high as 41%. In the UK, delivery by Caesarean section is recommended in women with primary or recurrent genital lesions at the onset of labour or pre-labour rupture of the membranes to minimize the risk of neonatal infection. However, in the Netherlands, vaginal delivery in women with recurrent lesions has not been shown to increase the incidence of neonatal herpes.
Blood-borne viral hepatitis Hepatitis B virus (HBV) carriage among pregnant women in the UK is in the region of 0.1^ 0.5% although it may be up to 1% in inner city areas re£ecting the higher proportion of women from areas with high endemicity (sub-saharan Africa, the far East and Paci¢c Islands).The infectivity of a carrier is determined by the presence of HBV e antigen (HbeAg) and antibodies to it (HbeAb). Women who are HbeAg positive are highly infectious and 90 ^95% of their infants will be infected and develop prolonged HBV carriage themselves. In contrast, only 5% of infants of women who are HbeAb positive will become carriers. The most common mode of transmission to the fetus is during delivery but in 5% of cases, transplacental infection occurs.Fetal HBV infection is not associated with an increased incidence of congenital malformations. Neonates born to women carrying HBV should receive a full course of vaccinations starting within 24 h of birth. Chronic infection with Hepatitis C virus (HCV) is increasingly being recognized in pregnant women. Five
INFECTIOUS DISEASE AND PREGNANCY
per cent of neonates of infected mothers will become infected and current evidence suggests that this ¢gure is not a¡ected by mode of delivery or by breast-feeding. There is currently no available vaccine.
Human immunode¢ciency virus Human immunode¢ciency virus (HIV) is the organism underlying the acquired immunode¢ciency syndrome (AIDS). Transmission from mother to fetus most commonly occurs during delivery, although transplacental passage may also occur. There is no speci¢c pattern of congenital abnormalities associated with congenital HIV infection but without intervention, around 15^35% of neonates will be found to have acquired infection. E¡ective strategies for reducing passage to the fetus during pregnancy and delivery are now available and every e¡ort should be made to identify women with HIV during the antenatal period so that prophylactic measures can be o¡ered and maternal therapy started. In developed countries, combination antiretroviral therapy is the standard treatment used as it reduces viral load and delays the emergence of viral resistance. This is usually continued during pregnancy and has not so far been associated with signi¢cant teratogenesis. E¡ective single agent prophylactic regimes with zidovudine or nevirapine have also been identi¢ed and may help reduce transmission in countries where combination therapy is prohibitively expensive. Delivery by Caesarean section and avoidance of breast-feeding also contribute to reduced transmission although the size of the reduction in women receiving other therapies remains unclear. Use of these strategies in combination can reduce the transmission rate to o2%.
Toxoplasma The UK prevalence of maternal infection withToxoplasma gondii is low at around 2 per 1000. Fetal infection occurs in the minority of cases of maternal infection but may result in severe congenital defects including hydrocephalus, mental retardation and retinochoroiditis. These may present at birth or become apparent later in life. In a study in a low prevalence, untreated population, similar to that in the UK, overall transmission to the fetus was 19% with 15% of infected fetuses showing congenital abnormalities by 1 year of age. Data from France, where the prevalence of toxoplasma infection is higher than in the UK, indicate that the risk of the fetus becoming infected and the risk of it being a¡ected both depend on the gestation at maternal seroconversion. The risk of infection increases from 2% at 8 weeks to around 75% at term. In contrast, the risk of the neonate manifesting congenital abnormalities in the ¢rst 3 years of life, a situation associated with high risk of long-term impairment, is greater if the earlier infec-
129
tion occurs. It should be noted that this study was carried out in France where mothers are commonly treated with spiramycin after the diagnosis of infection during pregnancy. Treatment with spiramycin from diagnosis of maternal infection onwards may be used to try to reduce the number of cases of congenital abnormalities associated with in utero infection. However, the e⁄cacy of spiramycin has never been tested in a placebo-controlled trial.There are no reports of signi¢cant side e¡ects associated with its use in pregnancy. In cases of proven fetal infection or high risk to the fetus (e.g. maternal seroconversion after 32 weeks), 3-week courses of pyrimethamine (50 mg/ 24 h), sulphadiazine (3 g/24 h) and folinic acid (20 mg/ 24 h) may be given alternating with spiramycin. Interval amniocentesis or fetal blood sampling may con¢rm fetal infection in utero. If infection is con¢rmed, ultrasound surveillance for abnormalities should be undertaken in order to detect the minority of fetuses that have been a¡ected. Ultrasound abnormalities are a late sign and serial scans are needed. The most common abnormality is cerebral ventriculomegaly (78% of fetuses with ultrasound abnormality) with other ¢ndings including intracranial calci¢cation, hepatomegaly and placental thickening or calci¢cation. Unfortunately, a lack of abnormality on USS does not guarantee that an infected fetus will be una¡ected although data on the size of this risk are not clear from the literature.
Syphilis Syphilis is caused by infection with Treponema pallidum. Fetal infection may occur during any stage of maternal infection but is more common (90%) in primary, secondary or early latent maternal infection than in late latent infection (10%). Although infection may occur at any stage of pregnancy, manifestations only occur in the fetus once it mounts an immune response from about 18 weeks of gestation onwards. Approximately 25% of infections end in fetal loss, 25% in preterm labour or intrauterine growth restriction and 50% in a congenitally infected neonate. Fetal infection may manifest on ultrasound as intrauterine growth restriction, hydrops fetalis, polyhydramnios or hepatomegaly. Infection can be con¢rmed by testing of amniotic £uid or fetal blood for Treponema pallidum antigen, although a negative result does not completely exclude infection. If maternal infection is diagnosed during pregnancy, treatment should be undertaken in conjunction with genitourinary medicine specialists so that contact tracing is not neglected. Antibiotic therapy is usually with high-dose penicillin. Erythromycin does not cross the placenta in adequate doses to treat the fetus and tetracycline should be avoided because of its potential e¡ects on bone and dentition. While treatment will cure fetal
130
infection it will not necessarily reverse existing fetal damage.
Listeria Maternal infection with Listeria monocytogenes may occur from ingestion of contaminated foodstu¡s, particularly unpasteurized dairy products, preprepared cook-chill meals, pa“te¤ and raw vegetables. Maternal infection is usually asymptomatic but may present as diarrhoea, in£uenza-like illness or as a febrile illness associated with preterm labour and meconium staining of the amniotic £uid. Con¢rmation of maternal infection may be sought by blood culture in febrile women. In a small but unde¢ned proportion of women with infection during pregnancy, the fetus will become infected during maternal bacteraemia. In early pregnancy, fetal infection may result in miscarriage while in later pregnancy fetal septicaemia may result in damage to multiple organs and stillbirth or neonatal death. It is not known to what extent maternal treatment may ameliorate the fetal effects, but treatment with ampicillin and gentamicin has been advocated.
CURRENT OBSTETRICS & GYNAECOLOGY (ROM), pyrexia 4381C in labour, ROM for 418 h prior to delivery or previous a¡ected child. This results in around 18% of women receiving antibiotics and 69% of cases being prevented although only 50% of mothers of infants with disease have been found to have a risk factor. At present there is no uni¢ed approach to antibiotic prophylaxis in the UK.
CONCLUSION Although the majority of infectious diseases in pregnancy does not result in signi¢cant harm to mother or fetus, the potential for this must not be forgotten. Managing such infections is a complex area, which should involve not only obstetricians but also fetal medicine specialists, microbiologists and physicians.
PRACTICE POINTS K
K
Group B Streptococcus Group B Streptococcus (GBS) is the most common lifethreatening neonatal infection in industrialized countries.GBS is found as a normal commensal in vaginal £ora in 10 ^20% of pregnant women. Around 40 ^70% of the infants of colonized mothers become colonized in the ¢rst week of life while a small number develop acute infection. Infection presents as sepsis, meningitis or pneumonia and is divided into early and late onset disease. Early onset disease is the result of vertical transmission of GBS. Neonatal mortality is around 10%, being signi¢cantly higher in preterm infants. Intrapartum antibiotic administration to high-risk mothers is e¡ective in reducing neonatal infection (penicillin G 3 g intravenously initially then 1.5 g 4 hourly until delivery). High-risk mothers may be identi¢ed by screening or a risk-based strategy. With screening, all women are o¡ered a vaginal swab at 35^37 weeks and those with a positive culture given intrapartum antibiotics. This would result in around 25% of women receiving antibiotics and prevent up to 90% of neonatal cases. With a risk-based strategy antibiotics are given to women in preterm labour, with preterm rupture of membranes
K
Puerperal sepsis remains a cause of maternal death and should be aggressively managed Investigation of infections that can a¡ect the fetus should be undertaken in consultation with a fetal medicine unit Testing for HIV infection should be actively encouraged because e¡ective interventions exist to reduced vertical transmission
FURTHER READING Brocklehurst P. Interventions aimed at decreasing the risk of mother-to-child transmission of HIV infection (Cochrane Review). In: The Cochrane Library, Issue 2. Oxford: Update Software, 2000. Drife J, Lewis G (eds).Why mothers die. Report on Con¢dential Enquiries into Maternal Deaths in the United Kingdom 1994 ^1996. London: The Stationery O⁄ce,1998. MacLean A, Regan L, Carrington D (eds). Infection and Pregnancy. London: RCOG Press, 2001. Nelson-Piercy, C. Handbook of Obstetric Medicine, 2nd edition. London: Martin Dunitz, 2002. Royal College of Obstetricians and Gynaecologists. Chickenpox in Pregnancy.Guideline Number 13, 2001. Sutherland S (ed). Torch screening reassessed: the report of a PHLS working party on diagnostic tests for congenital infections, 2nd edition. London: Public Health Laboratory Service,1993. Zuckerman AJ, Banatvala JE, Pattinson JR (eds). Principles and Practice of Clinical Virology, 4th edition. Chichester; John Wiley and Sons, 2000; 387^ 418.