Obstetric Perinatal Infections Lecture 5

1. Obstetric & Perinatal InfectionsLecture 5 1

2. Lecture overview Mechanisms of perinatal infections. Risks factors for maternal and child infections. Major perinatal pathogens and clinical problems. Examples of successful practices in prevention. Antenatal screening programmes in UK and USA. 2

3. Spectrum of infant infections 3

4. Mechanism of perinatal infections Infants can be infected by direct contact with: 1. Infected maternal secretions and mucous membranes, such as bacterial STI, herpes and papilloma viruses or UTI. Mother - vaginitis, amnionitis, or UTI. 2. Infected blood and cellular elements, such as Hepatitis B and C viruses, HIV. 4

5. Risks factors for maternal and child infections Absence of pre-natal care: Malnutrition, untreated infections – STIs. Difficult pregnancy, toxemia, prematurity. Prolonged rupture of membranes. Traumatic birth. Post-partum infections related to poor hygiene. 5

6. Aquired immunity 6

7. Examples of infections ToRCH TORCH ? Is a group of infectious diseases that can cause illness in pregnant women and may cause birth defects in their newborns. The test is a screen for the presence of any of the antibodies to these infections. Confirmation of an active infection may require more specific tests. Toxoplasma, Rubella, CMV, HSV 7

8. ToxoplasmaToxoplasma gondii Parasitic protozoa Host = cat Risk factors: ? Consumption raw/undercooked meat, contact cat faeces, contaminated water. Ingest cysts -> rupture in stomach -> releasing tachyzoites. Ingest oocysts -> hatch ->tachyozoites. 8

9. Toxoplasma, cont... Tachyozoite Invade all mammalian cell (except RBCs). Multiplys intracellularly. Destroys host. Spreads throughout body via bloodstream. 9

10. Seronegative Pregnant Women Likelihood/severity intrauterine infection depends on timing. 10

11. Maternal Symptoms of Infection Slight fever Aches Fatigue Rash (rare) Lymphadenopathy (commonest). 11

12. Congenital toxoplasmosis Infection early in pregnany; Chorioretinitis Cerebral calcification Hydro/microcephalus Infection late in pregnancy; Subclinical Chorioretinitis Hepatosplenomegaly Jaundice, rash 12

13. Diagnosis Pregnant mother Serology; IgM, IgG, seroconversion compared to booking blood. Antibody avidity PCR Foetus PCR Repeat serology IgM production may be delayed 2-3 months. Maternal IgG may be passively acquired. 13

14. Rubella Togavirus, ss RNA enveloped. Capsule Respiratory transmission. Viraemia 5-7 days post exposure. RNA Arrests cell division, destroys cells. Capsid Vaccine available, given in childhood as part of MMR. 14

15. Seronegative Pregnant Women 15

16. Maternal Symptoms of Infection About 50% asymptomatic Maculopapular rash Fever Lymphadenopathy Fatigue Sore throat 16

17. Congenital Rubella Syndrome Triad of abnormalities affecting eyes, ears & heart Micro-ophthalmia, glaucoma, pigmentary retinopathy. Sensorineural deafness. Ventricular septal defect, pulmonary artery/valvular stenosis, patent ductus arteriosis. 17

18. Diagnosis Pregnant mother Serology; IgM detectable 6-7 weeks post-infection, IgG, seroconversion compared to booking blood. Foetus Specific IgM Persistence of specific IgG 9-12 months PCR 18

19. Treatment/Prevention Live-attenuated virus vaccine as part of MMR given in childhood. Screening of pregnant women to determine immune status and advise accordingly. Vaccination post-partum for non-immune women. Only foetal intervention=termination. 19

20. Cytomegalovirus DNA virus of Herpesvirus family. Establishes in latent form in host, allowing periodic reactivation. Transmission via body fluids ie. Saliva. >90% adults immune. 20

21. Infection in Pregnant Women Reactivation of latent infection or primary infection. Foetal infection by reactivation less likely. 21

22. Maternal Symptoms Infection Normally asymptomatic Fever Headache Fatigue Myalgia Sore throat 22

23. Cytomegalic Inclusion Disease 90-95% develop normally Mild illness Interstitial pneumonitis Hepatosplenomegaly & jaundice Thromobocytopenia Purpura Classical, severe disease IUGR Chorioretinitis Sensorineural deafness Microcephaly CNS abnormalities 23

24. Diagnosis and treatment Pregnant mother Specific IgM (correlation between elevation and degree damage). CMV IgG avidity esp for reactivation. Foetus Specific IgM PCR 24

25. Herpes simplex virus HSV type 1 & 2. DNA virus of herpes virus family. Spread by sexual contact or oral transmission. 25

26. Congenital infection Maternal viraemia may occur rarely leading to congenital infection. If occurs <20w gestation 20-25% risk miscarriage Still birth Microcephaly, hydrocephalus, chorioretinitis, hepatosplenomegaly Neonatal infection during passage through birth canal more common. 26

27. Examples of viral infectionsVaricella Zoster virus DNA virus of Herpesvirus family. Spread by direct contact or airborne. Becomes latent and can be reactivated. Infectious before symptoms apparent. 27

28. Pregnant women >85% immune due to exposure in childhood. Infects placenta causing focal necrosis. CVS 2% risk if first 20w pregnancy. Miscarriage 3% if first 16 weeks pregnancy. Premature labour. 28

29. Congenital Varicella syndrome Microcephaly Cerebral cortical atrophy Cerebellar hypoplasia Mental retardation Convulsions Limb hypoplasia, malformed digits Skin scarring Cataracts, chorioretinitis, microphthalmia 29

30. Diagnosis and Prevention Pregnant mother Characteristic chickenpox. Culture/PCR of virus from vesicles. Foetal Specific IgM often undetectable at birth. Persistent specific IgG. 30

31. Parvovirus B19 DNA virus Causes erythema infectiosum, fifth disease or slapped cheek syndrome. Responsible for transient aplastic crisis in sickle cell anaemia. Transmitted by droplets (respiratory). Intense viraemic stage. Prediliction for rapidly dividing cells. Infects erythroid progenitor cells. 31

32. Congenital infection More pronounced during 2nd rather than 1st trimester. Severe and often fatal in foetus. ~9% foetal loss 4-6 weeks after development of rash in mother. Hydrops foetalis most common manifestation. Profound anaemia 32

33. Diagnosis and Treatment Pregnant mother Specific IgM. IgG seroconversion. Elevated serum a-feto-protein. Foetus Ultrasound for symptoms associated with hydrops and body cavities. PCR 33

34. Hepatitis B >2 billion exposed. 350-400 million chronically infected. Incubation period 45d to 180d. Acute fatality ~1%. Chronic fatality infected <5yo 30-90%. chronic fatality infected >5yo 2-10%. Vaccine introduced late 1980’s. High prevalence Africa/Asia. 34

35. HBV vertical transmission No evidence crosses placenta. Infection occurs intrapartum/perinatally. Risk determined by maternal HBe status. HBsAg +, anti-Hbe + low infectivity 10-25% risk. HBsAg+, HBeAg + high infectivity 90% risk. 35

36. Treatment and Prognosis 36

37. Hepatitis C Non-A non-B hepatitis or post-transfusion hepatitis. Named HCV in 1989. Often asymptomatic. Long incubation period to clinical endpoint. 6 genotypes. 37

38. HCV vertical transmission Some evidence intrauterine/perinatal acquisition. Maternal HCV RNA levels important predictive factor. Co-infection with HIV predisposes to transmission. Viral RNA found in breast milk but no recorded transmissions. Treatment and Prevention: No known method. Routine prenatal screening is not currently advised. Prevent contact with infected blood and organs. High-risk women should be screened. 38

39. Test infant at 1day, 6 weeks, 12 weeks of age. Loss of maternal AB should be confirmed at 18mo. Progression of disease assessed in same way as adults (CD4 count, viral load, clinical signs). 39 Treatment/Prevention, cont...

40. HIV More than 30 million worldwide HIV positive. Three strains recognised HIV-1, HIV-2 and HIV-O. More than 50% infected children present with lymphadenopathy/hepatosplenomegaly in first year life. About 30-50% diagnosed opportunistic infections, 48% expected to die before 3rd birthday. 40 Penumocystis carinii penumonia, tuberculosis, toxoplasmosis, cryptosporidiosis, candidiasis, herpes infections Anaemia in pregnancy . Intrauterine growth restriction. Preterm labour. Birth weight less than 2,500 g. Apgar score less than 7. Penumocystis carinii penumonia, tuberculosis, toxoplasmosis, cryptosporidiosis, candidiasis, herpes infections Anaemia in pregnancy . Intrauterine growth restriction. Preterm labour. Birth weight less than 2,500 g. Apgar score less than 7.

41. HIV vertical transmission Transmission rate 13-20% Europe, 25-30% Africa. Studies suggest infection can occur at any stage. Intrapartum most important. Risk factors include advanced stage maternal AIDS, presence of lesions, quality hygienic conditions surrounding birth. 41 Intrapartum: occurring during childbirth or during delivery.Intrapartum: occurring during childbirth or during delivery.

42. Diagnosis congenital HIV Maternal anti-HIV crosses placenta, persists up to 18m. Gold standard HIV DNA PCR on peripheral blood lymphocytes. +ve 72h birth = intrauterine transmission By 3mo 95% of those infected detected Maternal blood should be tested in parallel to check primers work. 42

43. Prevention If mother does not require HAART for own health = ZDV + 3TC + PI starting 24-28w gestation. Aim = reduce viral load <50 copies/ml 36weeks. If achieved vaginal birth or CS. Or ZDV monotherapy, planned CS at 38w, with ZDV infusion 4h prior. 43 ZDV=zidovudine 3TC=lamivudine PI=protease inhibitorZDV=zidovudine 3TC=lamivudine PI=protease inhibitor

44. If unable to achieve <50 copies/ml…resistance test performed, CS planned at 38w, ZDV infusion 4h prior, combination PEP prescribed to neonate, dose of NVP to mother. Avoidance of breast feeding. Reduced transmission rate from 25.6% to 1.2%. 44 Prevention, cont... NVP=nevirapine crosses placentaNVP=nevirapine crosses placenta

45. Syphilis Caused by Treponema pallidum. Cross the placenta. WHO estimates responsible for: 460 000 stillbirths/miscarriages. 270 000 congenital syphilis. 270 000 low birth weight/premature babies. 45

46. Syphilis vertical transmission Occurs after 16w. Greatest risk when in early stages of infection, but can be at any stage for transmission to occur. Access to the foetal compartment as early as 9–10 weeks. 46

47. Screening EIA on booking bloods. RPR or VDRL test combined with confirmation of reactive individuals with treponemal tests such as the FTA-ABS assay. High risk – repeat serologic testing – 3rd trimester and at delivery. 47

48. Clinical manifestations Hyperaemia and friability, during pregnancy may facilitate the entry and lead to spirochaetaemia. Histological changes of congenital and acquired syphilis are vasculitis and its consequences, necrosis and fibrosis. Solitary papule. 48

49. Clinical manifestations, cont... In about 2–6 weeks after the chancre resolves, systemic manifestations of the disease appear. The highly infectious condyloma latum found on the genitalia, mild hepatitis, and nephrotic syndrome. The mother transmit the infection transplacentally to the foetus or during passage through the birth canal. 49

50. Complications and treatment Syphilis can seriously complicate pregnancy and result in spontaneous abortion, stillbirth, non-immune hydrops, intrauterine growth restriction, and perinatal death. Early syphilis - Benzathine penicillin G 2.4 million units IM in a single dose. Late syphilis - Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals. 50

51. Listeria 51

52. Pathophysiology Ingestion of Listeria by pregnant women can result in nausea, vomiting, diarrhea, fever, malaise, back pain, and headache. Carried asymptomatically. Maternal infection can result in chorioamnionitis, premature labor, spontaneous abortion, or stillbirth. Foetal infection can occur via transplacental transmission. 52

53. Vertical transmission From mother to infant through an infected birth canal or ascending infection through ruptured amniotic membranes. Two clinical presentations of neonatal infections occur: - early onset (<5 d) – associated with sepsis or meningitis via transplacental transmission. - late onset (>5 d) - presents with purulent meningitis through vaginal transmission. 53

54. Clinical manifestations Listeria may proliferate in the placenta and cause infection due to impaired cell-mediated immunity during pregnancy. CNS infection is very rare during pregnancy. Fever, myalgias, arthralgias, back pain, and headache are classic symptoms of bacteremia. Listeriosis during pregnancy usually occurs during the third trimester. Preterm labour and/or delivery is common. Abortion, stillbirth, and intrauterine infection are possible. 54

55. Treatment Antibiotics – Ampicillin and aminoglycosides. Cephalosporins should not be used. Careful monitoring of the patient's temperature, respiratory system, fluid and electrolyte balance and nutrition. 55

56. Group B Streptococcus Known as Streptococcus agalactiae, is the causative agent of postpartum infection and as the most common cause of neonatal sepsis. Group B streptococci colonize the vaginal and gastrointestinal tracts in healthy women, with carriage rates 15%-45%. Neonates can acquire the organism vertically in utero or during delivery. Only 1-2% of colonized neonates develop invasive disease. 56

57. Group B streptococcal - prematurity and prolonged rupture of the membranes. Many pregnant women require treatment - Immunoprophylaxis and chemoprophylaxis. Pathogenesis: Disease is divided into early and late disease. Early sepsis often presents within 24 hours of delivery but can become apparent up to 7 days postpartum. Late sepsis between one week postpartum and age 3 months. 57 Group B Streptococcus, cont...

58. Prevention and treatment Intrapartum antimicrobial prophylaxis. Penicillin or ampicillin is the initial approach. Clindamycin and erythromycin are standard in individuals with penicillin allergy. 58

59. Chlamydia Chlamydia trachomatis - obligate, intracellular bacterium with 15 immunotypes: A-C - trachoma D-K - genital tract infections L1-L3 - lymphogranuloma venereum One of the leading causes of infertility in women. 59

60. Screening To prevent consequences of untreated chlamydial infection such as pelvic inflammatory disease, infertility and ectopic pregnancy. Screening for chlamydial infection in all pregnant women aged 24 years or younger and in older pregnant women who are at increased risk. 60

61. Pathophysiology Infection of the genital tract is the most common clinical presentation. The incubation period is 1-3 weeks. Chlamydia is transmitted via the birth canal of an infected mother, may develop conjunctivitis 5-13 days later. Pneumonia in the newborn. Chlamydial infection develops in 60% of neonates born vaginally to infected mothers. 61

62. Diagnosis Laboratory studies: Cell culture Direct fluorescent antibody Nucleic acid amplification techniques Enzyme immunoassay Specimens - urethra, endocervix, rectum, or conjunctivae. Treatment: First-line drugs - Azithromycin and doxycycline Second-line drugs - erythromycin 62

63. Diagnosis and Treatment of perinatal infections 1. Identify risk factors 2. Evaluate clinical features and laboratory support 3. Empirical or specific antimicrobial agents 4. Share information between obstetrical and pediatric/ family medicine providers 5. Post-partum follow-up 63

64. Antenatal screening in the UK Antenatal infection screening for HIV, hepatitis B and syphilis infections, and susceptibility to rubella for the benefit of the mother and to reduce vertical transmission. Uptake of screening increased since 2000 and reached 95.6% for HIV, 96.5% for syphilis, 96.2% for hepatitis B and 97% for rubella by the second half of 2007. The prevalence of HIV infection was 3.4/1,000 women, of hepatitis B (HBsAg-positive) was 11.3/1,000, of syphilis was 4.4/1,000 and of rubella susceptibility was 39.3/1,000. 64

65. UK Antenatal screening programmes 65

66. 66

67. UK Antenatal screening policy Test for HbsAg, HIV, Syphilis at time of booking (8-10 weeks). Repeat tests later in pregnancy if deemed high risk lifestyle. A false-negative result may occur if the woman is tested in the 12-week period. 67

68. 68

69. USA antenatal screening policy All women at first prenatal visit and high-risk women again at 28 weeks' gestation. All newborns older than 22 weeks' gestation whose mothers were not screened. Trace and contact all sexual partners of infected patients. All persons - close contact with early congenital syphilis before identification or during the first 24 hours of therapy should be examined clinically for the presence of lesions 2-3 weeks after contact. 69

70. HIV testing should be performed in all pregnant women during the first trimester . In pregnant women who have risk factors or who live in high-prevalence areas, a second HIV test should be considered during the third trimester . 70 USA antenatal screening policy

71. USA antenatal screening policy The CDC report that 22,000 women with HBV infection give birth each year. In 1984, the ACIP recommended that pregnant women at high risk for HBV infection be screened for HBsAg during a prenatal visit and, if found to be HBsAg-positive, that their newborns receive HBIG and HB vaccine at birth. 71

72. Mother - acute hepatitis, a history of exposure to hepatitis, or high-risk behaviour such as parenteral drug abuse has occurred during the pregnancy, an additional HBsAg test during the third trimester. Women who present for delivery without prenatal care or without medical records of HBsAg screening results, should have the HBsAg test done as soon as possible after admission. 72 USA antenatal screening policy

73. HBIG and HB vaccine treatment of all babies born to HBsAg-positive women is recommended. To prevent perinatal transmission, maternal screening, treatment of the newborn, and administration of subsequent doses of HB vaccine to the infant during pediatric visits at 1 and 6 months of age. If a serum specimen is positive for HBsAg, the same specimen should be tested again. 73 USA antenatal screening policy

74. Infants born to HBsAg-positive mothers should receive HBIG (0.5 mL) IM once they are physiologically stable, preferably within 12 hours after birth. 74 USA antenatal screening policy

75. Thank you 75