Perinatal Infections Fetal Infection

Nabeel BondagjiConsultant perinatologist

KFSH&RC Jeddah

Infections

Toxoplasmosis

Rubella

Varicella

Parvovirus

CMV

HIV

Syphilis

Introduction

3% of the perinatal mortalities are related to (fetal infection)Fetus can be affected at any gestational ageMost severe affection occurs in the first trimesterMost of the fetal infections are preventable

Red indicates the most vulnerable period of development. (Moore 143).

•First Trimester

Organogenesis

Growth restriction

•Second and Third Trimester

Neuological Impairment

Growth restriction

Think of fetal infection

I.U.G.R Hepatic Calcification Intracrainal Calcification Hydrocephally, Microcephally Ascits Pericardial,Pleural Effusion Non Immune Hydrops Fetalis

Toxoplasmosis

- Toxoplasmon gondii (intracellular parasite)

Trans-placental affect the placenta fetus

Transmission Rate

- 10 –15% 1st trimester

- 25% 2nd trimester

- 60% 3rd trimester

Toxoplasmosis

Toxoplasmosis

- Incidence of congenital toxoplasmosis

- 0.07 – 0.5 : 1000 London

- 2 : 1000 Brussels

- 3.22 : 1000 Paris

Risks to the Fetus

1st Trimester

- 55 – 85% will show sequilie

- Chrioretinitis severe impairment of vision

- Hearing loss

- Mental Retardation

- Ascits

- Periventirecular Calcification

- Hydrocephally

ToxoplasmonsisUltra Sound- Intracranial, hepatic, calcification- Ascitis- Hepatosplenomegally- Microcephally- I.U.G.R

Diagnosis Fetal Blood Sampling- IgM- PCR- Culture

Toxoplasmosis

Treatment

- Reduce risk of transmission

Spiramycin

- If fetal infection documented

- Pyrimethamine

- Sulfadiazine….. Folic acid

Pyron F, Wallonlion C, Goner P,Cochrane Database ReviewJanuary 2005

ObjectiveTo assess whether treatment of toxoplasmosis reduces the risk of congenital toxoplasmosis

Selection CriteriaRCT- Antibiotics- No treatment

Proven Infection

Look, outcome of the children

3332 Papers identified

NO Trial fulfill the criteria

ConclusionWe do not know whether antibiotics Treatment reduces the congenital transmission or not.Screening is ExpensiveScreening is not recommended in countries where screening and treatment is not routine.

Toxoplasmosis

Prevention to Toxoplasmosis: Advice to Pregnant Women whose Serological Tests are Negative.

Cook meat at 60oC + (Industrial deep-freezing also seems to destroy parasites efficiently).

When handling raw meat, do not touch eyes or mouth.

Cont.. Prevention of Toxoplasmosis

- Carefully wash hands after handling raw meat,

dirt, or vegetables soiled by dirt. - Wash fruit and vegetables before eating- Wear gloves when gardening- Avoid all contacts with things that may have

been contaminated by cat feces- If the cat’s litter has to be changed, put on

gloves and disinfect often with boiling water.

Rubella German Measles

Rubella

- 3rd Disease

RNA Virus

- Respiratory secretions

- 2 – 3 weeks I.P.

Rubella

- 0.5 – 2% Non Immune

- 0.2 – 0.5 Congenital Rubella Syndrome

Risk of Transmission

- 8 – 12 weeks 90%

-12 – 16 weeks 50%

- 16 – 20 weeks 17%

Rubella

Ultra Sound - I.U.G.R. - Hepto-splenomegally

Congenital Rubella syndrome- Eye

Cataract, Retinopathy Microphthalmia, glaucoma- Ear

Deafness-Heart PDA

Rubella

Diagnosis IgM

RUBELLA

Prevention Active immunization by vaccination is

the only efficient way of preventing congenital rubella.

Varicella Zoster Virus DNA Herpes- Chickenpox- Herpes Zoster- Incidence in pregnancy 0.4 – 0.7 : 1000 Maternal- Pneumonia increase mortalityFetal Congenital Varicella Syndrome in 1st tri mester- Skin Scar, Limb Hyproplasia- Chrioretinitis, Microcephally

Varicella

Neonatal Infection

Increase in Mortality

- 5 days before delivery – 48 hours post partum

- Avoid delivery if possible in this period

Diagnosis

Viral Culture

- PCR

Presence of infection does not predicate the severity of the

disease

VARICELLA

Prevention Passive immunization is currently available

and should be administered within 24-72

hours to sero-negative pregnant patients who

have been exposed to varicella.

Varicella

Treatment

- Oral cyclovir to improve sysmatic I.V. to treat pneumonia

- Safe in Pregnancy

- Does not prevent or decrease the fetal effect

- VZIG to be given to the neonate 5 days before delivery – 2 days postpartum

Varicella

Screening

- Not Recommended

Parvovirus B.19 the fifth disease

Infectious period 5 – 10 days after exposure

Mode of transmission

- Transplacental 33% transmission risk

- Fetal effect – abortion <20 weeks

- Hydrops fetalis 18% of all non immune

Intrauterine fetal infection Fetal effect of B19 : - A symptomatic -

IUGR - Congenital anomalies- Hydrops fetalis - IUFD

Parvovirus B 19 pathogenesis:a) Anemiab) Fetal myocardium

and hepatic affection c) Vasculitis

Diagnosis

Parpovirus

- ELISA

-Western blot test

IGM Diagnosis of Primary Infection

Elect Microscopy

- Direct Visualization of the virus or viral particles

Parvovirus

Fetal Diagnosis- PCR in A.F., Placenta & Blood

Ultra Sound- Hydropy Fetalis

Parvovirus

Prognosis and therapy

Survivor recovers normal

Fetal Therapy

Intravascualr Intrauterine Blood Transfusion

CMVDNA Herpes VirusMost common perinatal infection 0.2 – 2% of all newbornsLeading cause of hearing lossMode of transmissionContact with infected-Blood-Urine-Salvia-Sexual contact

CMV

I.P 28 – 60 days

Viremia 2 – 3 weeks

Maternal effect –

Asympathic, mild fever, malaise & myalgia

Primary infection 0.7 – 4%

Recurrent infection 13.5%

Epidimulogical Facts

Primary Infection

-Risk of Transmission 30 – 40%

-10% Seguilie of the infected

-30% Prenatal Mortality

-Of the survivor 80%will have neurological damage

Recurrent Infection

Transmission 0.1 – 2% Mostly a symptomatic most of the sequilie occurs as hearing loss

Diagnosis

CMV

Diagnosis Culture or PCR

– blood, urine & salvia

IgG Serial Measurements 3 – 4 weeks

Diagnosis either by seroconversion

Or increase titer by more than 4 folds

-1 : 4 – 1: 16

-1 : 16 – 1 : 256

IGM is not reliable as it may be negative even in the right phase and may persist for months after infections

Diagnosis

Fetal Diagnosis Ultra Sound System

- Intracrainal or hepatic calcification

- Echogenic bowel

- Ascits

A.F.

- Culture

- PCR

CMVTreatment- Not available- Neonatal therapy ganciclovir may decrease neonatal infectionsVaccine- May Reactivate A previous infectionCMVScreening

Not Recommended

Human immunodeficiency virus (HIV) Infection

This is the major cause of congenital

infection in the developing world.

Over one million children had been

infected from their mother by the end of 1998.

Mother child in utero at birth breast milk

Organ/tissue donation Semen Kidneys Skin, bone marrow, corneas, heart

valves, tendons, etc.

TO SCREEN OR NOT TO SCREEN?

The best defense is a strong offense.

The American Academy of Paediatrics and the ACOG issued a Joint Statement on HIV Screening in Pregnancy (1999) (2001).

A pregnant women should receive HIV counseling as part of their routine ANC.

A pregnant women should have HIV testing with their consent.

PRE-TEST COUNSELING

Risks of transmission (including Mode)

Risks of perinatal transmission

Potential social and psychological implication of Positive test.

The availability of Agents that may reduce the risk of neonatal infection.

Clarify the difference between HIV infection and disease.

Timing of Perinatal HIV Transmission

Cases documented intrauterine, intrapartum, and postpartum by breastfeeding In utero - 25% 40% of cases Intrapartum- 60% 75% of cases Addition risk with breastfeeding

• 14% risk with established infection• 29% risk with primary infection

Current evidence suggests most transmission occurs during the intrapartum period

Factors Influencing Perinatal Transmission

Maternal Factors HIV-1 RNA levels (viral load) Low CD4 lymphocyte count Other infections, Hepatitis C, CMV, bacterial

vaginosis Maternal infection drug use Lack of ZDV during pregnancy

Obstetrical Factors Length of ruptured membranes/chorioamnionitis Vaginal delivery Invasive procedures

Infant Factors Prematurity

Reducing HIV Transmission

with Suboptimal Regimens

Partial ZDV regimens: ( New York cohort) Transmission rates

• 6.1% with prenatal, intrapartum, and infant ZDV

• 10% with only intrapartum ZDV• 9.3% if only infant ZDV started within first

48 hours• 26.6% with no ZDV

Reducing Intrapartum HIV Transmission: Studies of Short

Course Therapy Oral ZDV in a non-breastfeeding population (Thailand) from 36 weeks and during labor Transmission rate: 9.4% ZDV vs. 18.9% placebo

PETRA study – intrapartum/postpartum oral ZDV/3TC in a breast-feeding population (Uganda, S. Africa, Tanzania) Transmission rate: 10% ZDV/3TC vs. 17% placebo

HIV Net 012 – intrapartum/postpartum/neonatal Nevirapine (NVP) vs. short course/neonatal ZDV in a breast-feeding population (Uganda) Transmission rate: 12% NVP vs. 21% ZDV

Treatment with zidovudine appears to be safe in pregnancy.

Elective caesarean section may decrease mother-to-child transmission.

HIV

Chochrane Database 2002

Objective to assess what intervention will decrease the risk of mother to children transmission of HIV

AZT4 trials decrease 1585 patientsNeviropine compared AZT 626 decrease transmissionC/S one trial 436 patients decrease risk of transmissionImmunoglbullinDoes not decrease the risk

Conclusion

Zidoridine, Nevirpine

C/S decreases the transmission significantly.

Syphilis

- T.P.

- Increase HIV

Transmission all through

Manifestation

Ultra Sound - Thick Placenta- Hydrops fetalis- I.U.G.R- Hydroamnios – Hepato-splenomegaly ……- Risk of Transmission

- 90% primary- 50% secondary- 6 – 14% Latent Syphillis

Diagnosis

Screening Non SpecificVDALRPRSpecific

TPHAF.T.A. becomes …..

3 – 4 weeks

Treatment

- Penicillin

- Benzathin Penicillin 2.4 million unit

- Erythpromycine

Thank You..Thank You..