Infection and Pregnancy - study group statement

Recommendations fall into three categories:

1. Recommendations for clinical practice (principally aimed at Fellows and Members of the Royal College of Obstetricians and Gynaecologists) based upon research evidence (where available) and the consensus view of the Group. The clinical practice recommendations have been graded from ‘A’ to ‘C’ according to the strength of evidence on which each is based (Table 34.1). The scheme for the grading of recommendations is based on the system adopted by both the NHS Executive and the Scottish Intercollegiate Guidelines Network.
2. Recommendations for future research in those clinical areas where the Group identified a need for further evidence on which to base practice.
3. Recommendations relating to health education and health policy.

Table showing Grading of recommendations

Recommendations for clinical practice

General

1. Sporadic miscarriage is so common that detailed infective screening cannot be justified economically. (Grade C)
2. TORCH screening is unhelpful and should be abandoned in the investigation of recurrent miscarriage. (Grade C)
3. To prevent preterm labour and mid-trimester loss, any screening for abnormal genital tract colonisation should be done in early pregnancy. (Grade C)
4. Pregnancies complicated by congenital infection should preferably be referred to regional fetomaternal medicine centres. (Grade C)
5. Maternal investigations for possible infection causes in cases of fetal hydrops, fetal brain lesions, unexplained severe growth restriction or in utero demise are recommended. (Grade C)
6. Infants with the suspicion of congenital infection and those born preterm, where infection may have played a role, need neurological follow-up by a competent paediatrician. (Grade C)

   Viral infections

7. All pregnant women presenting with a non-vesicular rash compatible with a systemic viral infection should be investigated for rubella and parvovirus B19 infection, irrespective of a prior history of rubella vaccination or previous positive rubella antibody tests. (Grade C)
8. All pregnant women with significant contact (defined as being in the same room for over 15 minutes or face-to-face contact) with a non-vesicular illness should be investigated for parvovirus B19 and rubella infection, irrespective of whether they develop a rash or not, unless there is satisfactory evidence of past rubella infection (two documented vaccinations, or one documented vaccination and one prior positive rubella antibody test, or two positive antibody tests). (Grade C)
9. All requests for laboratory investigation must give the following information in addition to the usual demographic details:
   • gestation of pregnancy (date of last menstrual period)
   • date of onset of rash, clinical features, type and distribution of rash
   • past history of rubella antibody tests or rubella vaccination
   • any known contact with rash illness and dates of contact. (Grade C)
10. Women found to be susceptible to rubella during prenatal screening or booking should receive appropriate vaccination before postnatal discharge. (Grade C)
11. When serology shows potential for early infection with parvovirus B19, the patient should be referred to a fetal medicine unit capable of fetal blood sampling and intravascular transfusion. (Grade C)
12. Amniocentesis is the method of choice for fetal sampling in the case of possible congenital infection but should be delayed until six weeks after maternal cytomegalovirus (CMV) seroconversion. (Grade A)
13. Neonates with congenital cytomegalovirus (CMV) infection and central nervous system signs at birth should be treated with ganciclovir according to the recent protocol from the Collaborative Antiviral Study Group. (Grade A)
14. Women without a previous history of varicella should be screened for varicella-zoster virus antibodies, by a sensitive method, at booking or rapidly after contact or exposure, i.e. within 48 hours, so that patients qualifying can receive VZIG (varicella-zoster immunoglobulin) within the designated window period for efficacy. (Grade C)
15. After a significant varicella or zoster contact, a susceptible pregnant women (regardless of gestational age) should be given VZIG (up to 10 days after contact). (Grade B)
16. VZIG should be given to newborns, born to mothers who develop varicella seven days before and up to seven days after delivery, and they should be followed up for any subsequent infection. (Grade B)
17. Mothers developing chickenpox should be counselled concerning the risks of fetal varicella syndrome (approximately 2% risk in the first 20 weeks) and a risk assessment undertaken for severe maternal varicella. (Grade C)
18. Oral aciclovir should be recommended to women over 20 weeks of gestation on the first day of the rash. Oral aciclovir should be offered to women at less than 20 weeks of gestation. Full informed consent should be obtained because, although the safety profile is reassuring, approval for use in pregnancy does not yet exist. (Grade C)
19. Hospital assessment and, where appropriate with an infectious diseases physician, intravenous aciclovir should be given to those patients with varicella pneumonitis and in those over 36 weeks of gestation or with clinical deterioration after day six of appearance of rash, to avoid the consequences of varicella pneumonitis and other serious sequelae. Varicella of the newborn should be treated with intravenous aciclovir, regardless of the previous administration of VZIG. (Grade C)
20. If a patient presents with a primary episode of herpes simplex virus (HSV) and is in labour, caesarean section is advised. (Grade B)
21. If a patient presents with a primary episode of HSV after 34 weeks, and before the onset of labour, she should be commenced on aciclovir and continued until delivery. If the interval between initiating therapy and delivery is more than four weeks, vaginal delivery is appropriate. (Grade C)
22. If a patient presents with a primary episode of HSV before 34 weeks, e.g. first or second trimester, she should be treated with aciclovir from 36 weeks until delivery, and vaginal delivery would not be contraindicated. (Grade C)
23. There is no evidence to support routine antenatal screening for HSV 1 and 2 antibodies, or for virus detection in the cervix from patients with a history or recurrent HSV. (Grade B)
24. There is no agreement on the use of caesarean section or aciclovir in the management of patients with a history of recurrent HSV. If a patient presents in early labour with a visible herpetic lesion, caesarean section is recommended. If a patient has frequent symptomatic recurrences during pregnancy, the use of aciclovir from 36 weeks is recommended, and vaginal delivery would not be contraindicated. (Grade C)
25. Voluntary testing for HIV should be an integral part of antenatal care, offered and recommended to all pregnant women. (Grade C)
26. HIV-positive women should be offered a package of care that includes: safe obstetric practices; anti-retroviral treatment to reduce the risk of mother-to-child transmission of HIV, to the fullest extent that is available; information on infant feeding risks and benefits; and supportive counselling. (Grade C)
27. The care of HIV-positive women should include appropriate postpartum care with access to contraception and follow-up medical care for the woman and her child. (Grade C)
28. Hepatitis B and C viral infections are not contraindications to breastfeeding. (Grade C)
29. Hepatitis B immunoglobulin should be given to babies of mothers of high infectivity, e.g. those who are hepatitis Be antigen-positive. (Grade C)

    Bacterial and other infections

30. Clinical trials of screening for and treatment of bacterial vaginosis have yielded conflicting results but treatment may reduce the risk of preterm birth in women with a previous preterm delivery. (Grade C)
31. There is no evidence to support the antenatal treatment of asymptomatic women colonised with the group B streptococcus (GBS). (Grade C)
32. Current recommendations are that all women with a history of having delivered an infant with GBS infection or of preterm rupture of the membranes, and all women found incidentally to have GBS in the urine or vagina during the current pregnancy should be offered intrapartum chemoprophylaxis. (Grade C)
33. Obstetricians must work with tuberculosis physicians to confirm and manage the disease. (Grade C)
34. Women with genital chlamydial infection need adequate chemotherapy and counselling, and a test of cure not less than three weeks after end of therapy. (Grade C)
35. Women with genital chlamydial infection must have contact tracing and appropriate management of their partners in a genitourinary medicine clinic. (Grade C)
36. Non-immune pregnant women should be advised against travel to a malarious area. If travel is unavoidable, advice should be given about personal protection and chemoprophylaxis. This advice also applies to previously immune women from malaria-endemic areas who have lived in the UK for more than two years and who will therefore have lost much of their pre-existing immunity. (Grade C)
37. Non-immune pregnant women with malaria need to be admitted to hospital, monitored closely (with particular attention to blood sugar and haemoglobin) and treated with an effective antimalarial such as quinine. (Grade C)
38. Recent immigrants from malaria-endemic areas are at risk of having placental malaria infection irrespective of whether they have a fever or peripheral parasitaemia. Malaria should be suspected and treated if women are anaemic or if there is evidence of intrauterine growth restriction. Unsuspected congenital malaria may occur in their infants with onset between birth and several weeks of age. (Grade C)
39. There is no evidence currently to support routine screening for toxoplasmosis during pregnancy in the UK. (Grade C)
40. Data from the Cochrane Library support the use of prophylactic antibiotics for emergency and elective caesarean sections, unless there are clear reasons why they should not be given. (Grade A)
41. The antibiotic used for prophylaxis before caesarean section should be limited to one dose to reduce the possibility of antibiotic resistance. (Grade A)
42. The only surgical technique which can be unequivocally recommended at caesarean section is the avoidance of manual removal of the placenta. (Grade A)
43. When infection develops and the patient is systemically ill, urgent and repeated bacteriological specimens, including blood cultures, must be obtained. The advice of a microbiologist must be sought at an early stage to assist with the use of appropriate antibiotic therapy. In serious cases, doctors should be prepared to give parenteral antibiotics before the diagnosis can be confirmed. (Grade C)
44. Until further evidence becomes available, the optimum treatment for postpartum endometritis is clindamycin and an aminoglycoside. (Grade A)

Recommendations for future research

1. Research is needed to identify those factors that predispose a mother and her fetus to be susceptible to common infections during pregnancy.
2. Research must continue into understanding the risks of mother-to-fetus transmission, timing of acquisition and impact on subsequent morbidity and mortality.
3. Further research is required into the mechanisms and relationship between infection and brain damage in preterm and term infants.
4. Research is needed to define the precise role of molecular techniques in the diagnosis of fetal infections.
5. Future research on infection in preterm labour should include a measure of host defence response to identify those women with abnormal genital tract colonisation who by nature of the inflammatory response they evoke are at greater risk of adverse fetomaternal outcome.
6. There is good evidence that antibiotic treatment of women with preterm, prelabour rupture of the membranes prolongs pregnancy, although it has not been shown to improve neonatal outcome. Consideration should therefore be given to antimicrobial therapy in this group.
7. Interventions, including the use of antibiotics active against bacterial vaginosis-related organisms, should be conducted as early as possible in the second trimester and should use the reduction of fetomaternal infection as an outcome parameter rather than preterm birth.
8. Future studies should focus on identifying additional co-factors to bacterial vaginosis for adverse pregnancy outcome, the optimal gestational age for screening and for intervention and the optimal choice of treatment (systemic or intravaginal clindamycin, or metronidazole with or without macrolide).
9. A large study is required to determine whether screening for asymptomatic bacteriuria continues to be relevant in improving pregnancy outcome.
10. If screening for asymptomatic bacteriuria does remain relevant, inexpensive but effective techniques are required.
11. Consideration should be given to screening all antenatal women before delivery, i.e. in the third trimester, for genital chlamydial infection, preferably using a nucleic acid amplification or similarly sensitive and specific test.
12. The British Paediatric Surveillance Unit is soon to publish the findings of a nationwide survey of GBS neonatal disease. It is apparent that accurate UK data are required on the incidence of neonatal GBS infection.
13. The development of a vaccine against toxoplasmosis should be supported.
14. A placebo-controlled trial in pregnant women with primary CMV infection should determine if selected antivirals with safe preclinical profiles can decrease intrauterine transmission.
15. A CMV vaccine should be developed and used for universal vaccination.
16. Research is needed on the long-term follow-up of infants who have developed fetal varicella syndrome.
17. Further research is required on fetal effects when parvovirus B19 infection occurs after 20 weeks, whether monitoring is necessary beyond 30 weeks, and whether cardiac sampling with or without transfusion is practical at less than 17 weeks of gestation.
18. Further information is required as to whether transmission of hepatitis C from mother to infant may be reduced by elective caesarean section.
19. The timing of administration of antibiotic prophylaxis needs further investigation, particularly in relation to cord clamping with respect to the patterns of neonatal sepsis and antibiotic resistance.
20. Alternative approaches to preventing post caesarean section infection need urgent evaluation, particularly surgical technique, use of antiseptic agents for vaginal examinations in labour and general infection control measures.
21. Antibiotic regimens currently used for treating endometritis in the UK should be compared with the current best regimen in future randomised controlled trials.

Recommendations for education and health policy

General

1. Mechanisms must continue to allow monitoring of the prevalence of clinically important infections among the pregnant population.
2. Quality assurance for current screening programmes is required.
3. Current routine screening programmes in the UK include testing for rubella, syphilis, hepatitis B and human immunodeficiency viruses. Any alterations or additions to these programmes must be based on sound scientific evidence, and reviewed by the National Screening Committee.
4. Doctors and midwives should be aware of the diverse technologies that are available in the modern laboratory for the diagnosis of infections in the pregnant women and the fetus.
5. Good communication between laboratory staff and doctors/midwives is essential to provide comprehensive care to the infected pregnant woman.
6. Consideration must be given to keeping appropriate samples of placenta and membrane for research into congenital and neonatal infection.
7. Consideration is needed of the role of screening for blood-borne viruses (HIV, hepatitis B virus, hepatitis C virus) prior to prenatal invasive diagnostic procedures. Any existing positive results should be noted and discussed with the woman because of the potential risk of fetal infection.
8. Puerperal sepsis is not a disease of the past and general practitioners and midwives must be aware of the signs and be prepared to institute immediate treatment and referral of any recently delivered woman with a fever and/or offensive vaginal discharge.
9. Clinicians must remain vigilant for early signs of invasive streptococcal disease. The signs of necrotising fasciitis are high fever plus swelling and marked tenderness localised to a muscle mass. Early treatment with antibiotics still seems to be the best way to prevent death.
10. Over 150,000 women die each year from puerperal sepsis. Medical treatment is often straightforward and inexpensive. Urgent action is needed by governments to make treatment available and accessible.
11. Worldwide about 100,000 women die each year from sepsis following abortion. Provision for safe abortion should be available to all women.

    Specific to particular organisms

12. GBS disease is the most frequent cause of infection in the neonate. Assessment of the risks of GBS disease for an individual mother and baby should be made by obstetricians and midwives, and timely and appropriate antibiotic prophylaxis considered where necessary. Guidelines should be in place and regularly audited.
13. There is insufficient evidence at present to recommend universal antenatal screening for GBS in the UK.
14. Any antibiotic administration to the mother in labour for GBS disease may have significant implications for the neonate and their subsequent management. Antibiotic choice and dose and timing should be considered carefully and the rationale and details communicated to the paediatricians caring for the neonate.
15. Clinicians must keep alert to the possibility of tuberculosis, particularly because of the difficulties in diagnosis, the high infectivity and the poor outcome if tuberculosis during pregnancy is not treated.
16. World Health Organization recommendations are that pregnant women (particularly those in their first and second pregnancies) living in malaria-endemic areas should receive antimalarial chemoprophylaxis or intermittent treatment with an effective antimalarial.
17. In observational studies, bacterial vaginosis is associated with second-trimester loss and preterm birth. Bacterial vaginosis can be diagnosed by composite (Amsel) criteria or Gram stain (Nugent score).
18. Appropriate health information about toxoplasmosis should be given to all pregnant women.
19. Reconsideration should be given to using hepatitis B immunoglobulin if the mother is of low infectivity, i.e. hepatitis Be antibody-positive.
20. Hepatitis E should be considered if a pregnant woman develops acute hepatitis after recently returning from an endemic area.
21. Pregnant women who develop a rash or have known exposure to parvovirus B19 should be seen promptly to assess serological status.
22. When fetal hydrops is found, the possibility of parvovirus B19 as a treatable cause must be considered.