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Infection of the foetus and newborn Professor M. Cafferkey Consultant Microbiologist, The Rotunda.

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Presentation on theme: "Infection of the foetus and newborn Professor M. Cafferkey Consultant Microbiologist, The Rotunda."— Presentation transcript:

1 Infection of the foetus and newborn Professor M. Cafferkey Consultant Microbiologist, The Rotunda

2 Consequences of Infection l Consequences to the infected host »acute manifestations, chronic infection, other sequelae l Vertical Transmission »mother to infant l Horizontal transmission »family, others people, healthcare workers

3 Intrauterine Infection Infections in pregnancy are common: Which infections, if acquired in pregnancy, may harm the foetus ?

4 Definitions l congenital »contracted in utero l perinatal »from completion of 28 weeks gestation until 1-4 weeks after birth l postnatal l neonatal

5 Intrauterine & Perinatal Infection l infection diagnosed in utero l congenital infection, symptomatic or asymptomatic at birth l acquired around the time of birth and manifest later

6 Effect of Maternal Infection upon the foetus l no evidence of damage l subclinical infection without evidence of damage l abortion l foetal death l stillbirth l death in infancy l intrauterine growth retardation (IUGR) resulting in low birth weight (LBW) l congenital defects l late onset of congenital disease or defects

7 Congenital and Perinatal Infection 1.Diagnosed in utero 2.Congenital infection may be asymptomatic or symptomatic at birth 3.Infection acquired around the time of birth may manifest later

8 Common Infecting Agents l Viruses l Bacteria l Protozoa l Rickettsiae/Chlamydiae l (Fungi are very very rare, as a cause of intrauterine infection – an increasing cause of late-onset neonatal sepsis)

9 Intrauterine & Perinatal Infection Diagnosed in utero Parvovirus B19 Manifest at Birth Toxoplasma gondiiRubella CytomegalovirusVaricella/Zoster Treponema pallidumhepatitis B hepatitis CHIV

10 Intrauterine & Perinatal Infection Acquired around the time of birth and symptomatic later Herpes simplexhepatitis B hepatitis CHIV Group B  haemolytic streptococci E. coli (+)Listeria monocytogenes Chlamydia trachomatis Neisseria gonorrhoea

11 Torch Syndrome Toxoplasma Others (Varicella/Zoster & Tr. pallidum Rubella CMV Herpes simplex These agents are grouped together “for convenience”

12 Prevention l Requires a knowledge of the route and mechanisms of infection, and the period of transmission of infection to the foetus/neonate

13 Intrauterine and Perinatal Infection Mechanisms: l Intrauterine »Blood borne transplacental infection »Ascending infection l During delivery l Postnatal infection »breast milk »cross infection »the environment

14 Period of transmission

15 Intrauterine Infection: What you should know l The risk posed by the agent to the foetus l Timing of infection in relation to risk l Frequency of Damage l Nature of Damage l Availability of diagnostic tests l Whether treatment is available l Preventive measures

16 Protect the mother: Protect the foetus l Education l Medical »standard precautions »screening - Bacteruria ? »Serological screening »Screening for GBS carriage (controversial outside North America and AUS)

17 A ntenatal screening - Definition of screening: l The systemic application of a test or enquiry l to identify individuals at sufficient risk of a specific disorder to benefit from further investigation or direct preventive action, l among people who have not sought medical attention on account of symptoms of that disorder

18 Antenatal Screening: Justification l Will give information “for action” to prevent or reduce the adverse consequences of the infection l Treatment or prophylactic measures will usually be instituted Problems with screening for infection: it gives a “snapshot” in time l Women remain at risk of acquiring infection during the pregnancy - ? Repeat tests l A woman may be in the “window period” before signs of the infection appear


20 Examples of types of Congenital Infection - Included in routine antenatal screening programmes? YESNO Rubella CMV HBVherpes simplex HIV parvovirus B 19 Syphilis

21 Congenital Infection: specific examples

22 Rubella An RNA togavirus l 1938viral aetiology suggested l 1941McAlastair Greig suggested an association between maternal rubella, congenital heart disease and cataracts l 1962virus isolated l 1969live vaccine developed

23 Timing of infection: Risk of damage Infection at l 0-8 weeks 80% detectable defects l 9-12 weeks 52% detectable defects l 13-20 weeks 16% ? l 20+ weeks no increased risk

24 Rubella: Nature of Damage Rubella Syndrome l PDA l Cataracts l Hearing deficits l Encephalitis l Interstitial pneumonia l Sensory abnormalitis: Eye/Ear l Bony radiolucencies Expanded Rubella Syndrome l Small for Gestational age l Microcephaly l PDA l Pulmonary Stenosis l Hepatosplenomegaly/ lymphadenopathy

25 Congenital Rubella l Retinopathy with retinal degeneration in the region of the macula and characteristic clumping of pigment

26 Rubella l Routine infant immunisation, now as MMR at 15 months and 4 years l Routine screening test in pregnancy - a convenient time to screen healthy normal women l Women who are non-immune are offered vaccine postnatally l [pre-conceptual screen, premarital screen]


28 Cytomegalovirus The most common congenital infection worldwide; predominantly due to primary maternal infection

29 CMV retinitis l Haemorrhages, sheathing of blood vessels and white fluffy areas of retinal infiltration

30 Congenital CMV l The most common congenital infection worldwide; rate estimated at 0.5 to 2.5% l 95% are asymptomatic at birth, 10-15% may develop symptoms later l Microcephaly, hydrocephaly l periventricular cerebral calcification l deafness, cerebral palsy l Seizures l microphthalmia l chorioretinitis, blindness l interstitial pneumonia l petechiae/purpura l anaemia, HSM, lymphadenopathy

31 Congenital CMV l Prevention - there is no proven preventive intervention l Treatment - There is limited evidence that treatment of infants with neurologic symptoms, with ganciclovir iv x 6 weeks, may help, however when the drug is stopped the viral load increases again

32 Congenital toxoplasmosis

33 Toxoplasmosis Toxoplasma gondii l The cat is the primary host l Other animals and birds l 24% of Irishwomen have antibody indicating previous infection l Human infection is believed to result from eating undercooked infected meat or handling infected soil or cat litter

34 Congenital Toxoplasmosis l Classic triad »hydrocephalus, intracranial calcification & chorioretinitis l non-specific signs »hepatosplenomegaly, jaundice »thrombocytopenia, »growth retardation, rash

35 Congenital Toxoplasmosis l Retinal scar with surrounding pigment

36 Sequelae l Only 10% of infected babies are clinically symptomatic at birth l The most common clinical sequel is chorioretinitis »by the age of 20, 60-85% have had chorioretinitis which may be unilateral or bilateral l Deafness, low IQ

37 Treatment of CT l In utero diagnosis and treatment »France, Austria, Switzerland »few controlled studies »Meta-analysis “5 studies showed that antenatal treatment was effective, four that it was not” Wallon et al., BMJ, 1999, 318, 1511-4 l Postnatal diagnosis and treatment »treatment for the entire first year of life will improve outcome McLeod and the Toxoplasma Study Group

38 Treponema pallidum

39 Congenital syphilis l Foetal death and miscarriage l Stillbirth l Congenital infection which may be asymptomatic at birth and manifest later

40 Congenital Syphilis l Most likely to occur if a mother has untreated primary infection in this pregnancy l The risk of transmission decreases with subsequent pregnancies

41 Rash - congenital syphilis

42 Congenital syphilis l discrete macular lesions similar to those seen IN secondary syphilis

43 Congenital syphilis l Interstitial keratitis

44 Positive treponemal serology l Treat mother unless previous treatment and serological response has been documented l Repeat serology monthly l Screen for other STDs l Partner referral to GUM/ID service l Assess infant »Dependant on maternal results and treatment, X-rays and CSF exam may be required in infant l Treat the infant in virtually all cases »one dose, 10 days, 14 days regimen dependant on circumstances

45 Listeriosis Listeria monocytogenes l A zoonosis l soft cheeses, pate l Infection in utero may result in stillbirth or a live infant with congenital infection l Uncommon, however it the third most common organism causing Early Onset neonatal infection

46 Maternal or Neonatal Listeriosis l Prevalence in Ireland unknown l Rotunda 1993 – 2001: »approximately 58,000 births »two mothers with L. monocytogenes septicaemia, and 1 mother with a clinical diagnosis of listeriosis: c. 1 in 20,000 »no cases of neonatal sepsis with L. monocytogenes

47 Parvovirus B19 l “Slapped Cheek Syndrome” or Fifth Disease l A common febrile exanthematous infection of childhood l Symptoms include a “lacy” rash, influenza- like symptoms and arthropathy l Some 50% of women of child-bearing age are immune

48 Parvovirus B19 l When acquired by a non- immune pregnant woman the transmission rate to the foetus is about 33% l anaemia, cardiomyopathy, hepatic dysfunction, hydrops foetalis - foetal death may occur l Diagnosis by specific IgM l Exchange transfusion in utero is appropriate therapy in severe cases

49 Parvovirus B19 l “B19 multiples in the bone marrow where it is cytotoxic for erythroid progenitor cells; this results in temporary arrest of erythropoiesis” - this effect is not typically seen in the normal child or adult l Severe anaemia is most frequent with infection of the foetus and in individuals with chronic haemolytic anaemias such as sickle-cell disease l myocarditis occasionally reported

50 Varicella zoster virus l Infection in the first 20 weeks may result in the congenital varicella syndrome l The risk of CVS with chickenpox in the first 20 weeks is approx. 2% l Acute varicella in the time period from 2 days before to 5 days after delivery is associated with a high risk of severe disseminated varicella in the newborn

51 Varicella zoster l In general, exposure to zoster, or the appearance of maternal zoster does not lead to foetal infection

52 Varicella zoster: Prevention l Specific VZ immunoglobulin if administered within 96 hours of exposure will usually modify the illness l If administered up to 9 days there may be attenuation

53 Varicella zoster: Prevention l The principal reason for VZIG administration in pregnancy is to modify the illness in the mother; there is little evidence that it will influence the development of the congenital varicella syndrome

54 Varicella zoster: Prevention l If a mother has chickenpox in the time period 2 days before to 5 days after delivery, the infant should be given VZIG and carefully observed; if any lesions develop, iv aciclovir should be given

55 Perinatal Viral infection l Cytomegalovirus l herpes simplex l hepatitis B l human immunodeficiency virus

56 Herpes simplex l The principal risk of transmission is with primary maternal infection at the time of delivery l The risk is smaller with recurrent herpes at time of delivery

57 Prevention of neonatal herpes l Recognition l Elective section in primary herpes at term or <4 hours after membrane rupture l Some obstetricians would also recommend elective section when recurrent genital herpes is present at term

58 Primary herpes of the cervix

59 Herpes simplex l Recognition of primary herpes can require a high index of suspicion l type 1 infection typically produces less severe symptoms and relatively little local manifestation compared with type 2 infection l the infection may be confined to the cervix

60 Hepatitis B

61 l Chronic HBV infection with persistence of HBsAg occurs in »up to 90% on infants infected vertically, »30% of children 1 to 5 years old infected after birth »in 5 to 10% of older children, adolescents and adults with HBV infection


63 Hepatitis B l The development of the carrier state following vertical transmission has been estimated to  the risk of chronic liver disease x20 times & hepatoma x86 times l In addition, horizontal transmission of the infection may occur in childhood; est. that vaccinating one child protects 3 others

64 HBV: Perinatal Transmission l Baby should receive Hepatitis B vaccine l Administration of HBIG will further reduce the risk of transmission

65 HBV: Prevention of vertical transmission l Routine linked antenatal HBV testing would be cost-effective because of the morbidity prevented by identifying carrier mothers and giving immunoprophylaxis to their infants l This is the case even in areas of low endemicity such as all of N Europe


67 Hepatitis C l Most transmission is around the time of birth l Rotunda studies: Vertical transmission rate = 6.7% l Outcome - may become chronic carriers l Identify mothers at risk

68 Human Immunodeficiency Virus

69 HIV - Vertical Transmission l perinatal in most cases l transmission rate 15 - 25% l Role of Caesarean section in reduction of transmission in some cases

70 HIV - Vertical Transmission l transmission can be decreased by approximately 2/3 by administration of anti-retrovirals »to the mother in pregnancy (po), in labour (iv and po) & »to the infant for the first 4 weeks (po) - this is post-exposure prophylaxis

71 HIV - Antenatal testing Unlinked testing indicated that only 25-50% of HIV+ women were identified Routine anti-HIV testing introduced Rotunda January 1998 National programme commenced April 1999, based on the Rotunda model

72 HIV l >90% of cases of paediatric HIV are due to vertical transmission l prevention is dependent on identification of infected mothers and »antiretroviral therapy, antepartum and intrapartum with post-exposure prophylaxis to the infant »caesarean section in selected cases

73 Chlamydia trachomatis l Acquisition occurs in some 50% of infants born vaginally to infected mothers and in some delivered by CS with intact membranes l The nasopharynx is the common site of primary multiplication in the infant »conjunctivitis in 15-50% »pneumonia in 5 - 20%

74 Chlamydia: Prevention l Opportunistic screening of women “at risk” »DNA detection methods suitable for use on urine specimens l UK DOH recommendation »All women attending STD clinics »single women < 25 years »women with multiple sex partners »women with a new sex partner

75 Neonatal Sepsis

76 Perinatal infections: in the hospital l sepsis l meningitis l pneumonia l urinary tract infection l conjunctivitis l omphalitis l otitis media

77 Perinatal infections: in the community l skin infections  omphalitis l bronchiolitis  pneumonia l diarrhoeal disease l otitis media l urinary tract infection l conjunctivitis (orbital cellulitis) l sepsis l meningitis

78 Diagnosis of Neonatal Sepsis l Difficult l Signs are Subtle and Non-specific »respiratory distress »lethargy »poor feeding »jaundice »vomiting & diarrhoea

79 Risk Factors l Maternal History »Traumatic delivery »Prematurity »Maternal Peripartum Sepsis »Prolonged Rupture Of Membranes

80 Risk Factors »Prolonged Rupture Of Membranes –ROM >24 hours:Infection rate of 1/100 –ROM with Chorioamnionitis: Infection rate of 10/100 –Irrespective of the time interval, membrane rupture - delivery, infection rates are 5 times higher in infants born before term

81 Characteristics Early-Onset l Within first 24 hours, range (0 - 6d) l Fulminant, Multisystem, Pneumonia frequent l Mortality rate of 15- 50% Late-onset l at 3 to 4 weeks, range 7d to 3 mo l Slowly progressive, l Focal; Meningitis frequent l Mortality rate of 10- 20%

82 Neonatal sepsis “The big three” l Group B strep l E. coli »and other Gram negative bacilli such as Proteus, Klebsiella l Listeria monocytogenes Others including: l Staph aureus l coagulase- negative staphylococci l Candida species l Pseudomonas l Enterobacter

83 Neonate with pneumonia and empyema due to E. coli

84 20 day old infant osteomyelitis due to E. coli following early-onset sepsis

85 Neonatal sepsis: problems Difficulties with making a laboratory diagnosis l Mother had antibiotics l Infant has received antibiotics l Small sample size, especially in the premature or growth retarded infant l Frequent isolation of “normal flora”

86 Neonatal Sepsis l Many neonatologists/units perform screening swabs l ear swab, umbilical swab, gastric aspirate, in addition to blood culture

87 GBS infection - Prevention l Early-Onset GBS infection is primarily an intra-uterine infection l Therefore it may be prevented by intrapartum chemoprophylaxis l In Late-Onset GBS infection the route of entry is unclear l This is not amenable to prevention by chemoprophylaxis

88 Group B streptococcus l Historically the case-fatality rate has been estimated to be 5-20% for neonates and 15-32% for adults l Fatality rate in early-onset sepsis in the most recent studies was 6%. This reduction in rates may be because of advances in neonatal care

89 GBS Epidemiology l Reservoir - Gastrointestinal tract l The genitourinary tract is the most common site of secondary spread l Colonisation rates may vary by geographical area, race and age l In most populations studied 10-30% of pregnant women were colonised

90 GBS Epidemiology l Neonatal disease: “1 to 4 cases /1,000 live births” l USA 1990, multistate surveillance 1.8 cases /1,000 live births l In general, Early-onset accounts for >75% of neonatal cases

91 GBS Surveillance l GBS disease in infants less than 90 days of age UK and ROI l Results of Year 1 –67% < 7 days –Overall 0.73/1,000 LB; 0.48 EO, 0.25 LO –ROI total 0.63/1,000; 0.34 EO, 0.29 LO –Overall EOS sepsis 62%, pneumonia 28% –Overall LOS meningitis 42%, sepsis 41%

92 RSV Bronchiolitis l Seasonal l more severe in infants with respiratory compromise l prevention l avoid crowds and handling!! l RSV IG, Who to treat ???

93 Rotavirus gastroenteritis l Common worldwide l may be very severe l Prevention: vaccine now withdrawn because of unexpected side effect - increased incidence intussusception

94 Control & Prevention of Congenital, Perinatal & Neonatal infection

95 Control & Prevention General Medical l precautions with clinical examination l use of standard / universal precautions when coming into contact with blood or secretions that may contain blood

96 Prevention of congenital and perinatal infection l Serological screening in pregnancy »Rubella, syphilis, Hepatitis B, HIV: “routine” »Hepatitis C: in certain groups Q VZV l Handwashing »CMV, toxoplasmosis l Modification of “at risk” behaviour »Blood borne viruses »Sexually transmitted infection

97 Prevention of congenital and perinatal infection l Avoidance of certain foods »pate, soft cheeses, undercooked meats l Screening for GBS carriage is performed in USA and AUS »from 35 weeks »intrapartum penicillin in carriers and those who deliver earlier (not screened) l Active herpes at term - avoid vaginal delivery

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