Perinatal Infections Fetal Infection Nabeel Bondagji Consultant 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 age Most severe affection occurs in the first trimester Most 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%1 st trimester - 25%2 nd trimester - 60%3 rd trimester

Toxoplasmosis - Incidence of congenital toxoplasmosis – 0.5 : 1000 London - 2 : 1000 Brussels : 1000 Paris

Risks to the Fetus 1 st Trimester - 55 – 85% will show sequilie - Chrioretinitis severe impairment of vision - Hearing loss - Mental Retardation - Ascits - Periventirecular Calcification - Hydrocephally

Toxoplasmonsis Ultra 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 Review January 2005 Objective To assess whether treatment of toxoplasmosis reduces the risk of congenital toxoplasmosis Selection Criteria RCT - Antibiotics - No treatment Proven Infection

Look, outcome of the children 3332 Papers identified

NO Trial fulfill the criteria

Conclusion We do not know whether antibiotics Treatment reduces the congenital transmission or not. Screening is Expensive Screening 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 60 o C + (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 - 3 rd Disease RNA Virus - Respiratory secretions - 2 – 3 weeks I.P.

Rubella – 2% Non Immune – 0.5 Congenital Rubella Syndrome Risk of Transmission - 8 – 12 weeks90% -12 – 16 weeks50% - 16 – 20 weeks17%

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 mortality Fetal Congenital Varicella Syndrome in 1 st 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 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) Anemia b) 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

CMV DNA Herpes Virus Most common perinatal infection 0.2 – 2% of all newborns Leading cause of hearing loss Mode of transmission Contact 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 : 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

CMV Treatment - Not available - Neonatal therapy ganciclovir may decrease neonatal infections Vaccine - May Reactivate A previous infection CMV Screening 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

AZT 4 trials decrease 1585 patients Neviropine compared AZT 626 decrease transmission C/S one trial 436 patients decrease risk of transmission Immunoglbullin Does 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 Specific VDAL RPR Specific TPHA F.T.A. becomes ….. 3 – 4 weeks

Treatment - Penicillin - Benzathin Penicillin 2.4 million unit - Erythpromycine