INFECTION IN PREGNANCY

TORCH

Horizontal transmission

Vertical transmission
Congenital infection
Perinatal infection
Neonatal infection
Postnatal infection
Mode of Transmission
Infection during pregnancy:

Transplacental infection

Non placental infection:
Ascending infection
Intrapartum infection
Postnatal infection
General Principles
Pregnancy does not alter resistance to infection
Severe infections have greater effects on the
fetus
Maternal antibodies cross the placenta and give
passive immunity to the fetus
Fetus becomes immunologically competent
from the 14th week
Fetus and Infection
Indirect effect - O2 transport, nutrient
exchange

Direct effect - invasion of placenta and
infection of fetus
Viruses more than bacteria
rarely effect fetus unless maternal infection is severe
exception: Rubella, CMV, Herpes Simplex
Fetus and Infection
Infections cause
- miscarriage
- congenital anomalies
- fetal hydrops
- fetal death
- preterm delivery
- preterm rupture of the membranes
TORCH

T = Toxoplasma gondii
O= Others
R= Rubella Virus
C= Cytomegalovirus
H= Herpes Simplex Virus
Toxoplasmosis
Caused by protozoan Toxoplasma gondii
Domestic cat is the definitive host with infections via:
Ingestion of cysts (meats, garden products)
Contact with oocysts in feces
Much higher prevalence of infection in European
countries (ie France, Greece)
Acute infection usually asymptomatic
1/3 risk of fetal infection with primary maternal
infection in pregnancy
Infection rate higher with infxn in 3
rd
trimester
Fetal death higher with infxn in 1
st
trimester
Toxoplasma Infection

Acquired infection
immunocompetent individuals:
Asymptomatic or very mild infection
immunocompromised individuals:
high risk of fatal disseminated infection;
often reactivation

Congenital infection (in pregnancy):
- high risk of fetal damage or death after
- primary infection during pregnancy
Risk Factors for Congenital Toxoplasmosis
Primary Toxoplasma infection during pregnancy:

no known risk for congenital infection of infants
born to immune women

no known risk of congenital infection in case of
primary infection before conception

Time point of infection during pregnancy
Clinical Manifestations
Most (70-90%) are asymptomatic at birth
Classic triad of symptoms:
Chorioretinitis
Hydrocephalus
Intracranial calcifications

Other symptoms include fever, rash, HSM, microcephaly,
seizures, jaundice, thrombocytopenia, lymphadenopathy,
premature-birth, still-birth/IUFD

Initially asymptomatic infants are still at high risk of
developing abnormalities, especially chorioretinitis

Chorioretinitis of congenital toxo
Diagnosis
Maternal IgG testing indicates past infection
(but when?)
Can be isolated in culture from placenta,
umbilical cord, infant serum
PCR testing on WBC, CSF, placenta
Not standardized
Toxo Screening
Prenatal testing with varied sensitivity not
useful for screening

Neonatal screening with IgM testing
implemented in some areas
Identifies infected asymptomatic infants who may
benefit from therapy
Treatment
Treatment for pregnant mothers diagnosed
with acute toxo
Spiramycin daily
Macrolide antibiotic
Small studies have shown this reduces likelihood
of congenital transmission (up to 50%)

If infant diagnosed prenatally, treat mom
Spiramycin, pyrimethamine (anti-malarial,
dihydrofolate reductase inhib), and sulfadiazine
(sulfa antibiotic)
Leucovorin rescue with pyrimethamine
Syphilis
T.Pallidum
<1:1000 pregnant women
Can infect trans placenta from 15
th
week
Second stage by birth if not treated
Screening VDRL, RPR
Diagnostic tests TPI, FTA-Abs
High dose Penicillin's
Syphilis
Treponema pallidum (spirochete)
Transmitted via sexual contact
Placental transmission as early as 6wks gestation
Typically occurs during second half
Mom with primary or secondary syphilis more likely to
transmit than latent disease
Large decrease in congenital syphilis since late 1990s
In 2002, only 11.2 cases/100,000 live births reported

Congenital Syphilis
2/3 of affected live-born infants are
asymptomatic at birth
Clinical symptoms split into early or late (2
years is cut off)
3 major classifications:
Fetal effects
Early effects
Late effects
Clinical Manifestations
Fetal:
Stillbirth
Neonatal death
Hydrops fetalis
Intrauterine death in 25%
Perinatal mortality in 25-30% if untreated
Clinical Manifestations
Early congenital (typically 1
st
5 weeks):
Cutaneous lesions (palms/soles)
HSM
Jaundice
Anemia
Snuffles
Periostitis and metaphysial dystrophy
Funisitis (umbilical cord vasculitis)
Periostitis of long bones seen in
neonatal syphilis
Clinical Manifestations
Late congenital:
Frontal bossing
Short maxilla
High palatal arch
Hutchinson teeth
8
th
nerve deafness
Saddle nose
Perioral fissures
Can be prevented with appropriate treatment
Hutchinson teeth late result of
congenital syphilis
Diagnosing Syphilis
(Not in Newborns)
Available serologic testing
RPR/VDRL: nontreponemal test
Sensitive but NOT specific
Quantitative, so can follow to determine disease activity and
treatment response
MHA-TP/FTA-ABS: specific treponemal test
Used for confirmatory testing
Qualitative, once positive always positive
RPR/VDRL screen in ALL pregnant women early in
pregnancy and at time of birth
This is easily treated!!
Definition of Congenital Syphilis
Confirmed if T. pallidum identified in skin lesions,
placenta, umbilical cord, or at autopsy
Presumptive diagnosis if any of:
Physical exam findings
CSF findings (positive VDRL)
Osteitis on long bone x-rays
Funisitis (barber shop pole umbilical cord)
RPR/VDRL >4 times maternal test
Positive IgM antibody
Treatment
Penicillin G is THE drug of choice for ALL syphilis
infections
Maternal treatment during pregnancy very effective
(overall 98% success)
Treat newborn if:
They meet CDC diagnostic criteria
Mom was treated <4wks before delivery
Mom treated with non-PCN med
Maternal titers do not show adequate response (less than
4-fold decline)
Rubella
Togavirus: single-stranded RNA virus
Incubation - 14-21 days
Respiratory droplet inoculation
only modestly contagious
Fever, rash (3 days), cough, arthralgias, post auricular
and suboccipital lymphadenopathy
Usually mild, overt clinical symptoms 50-75% of
cases
Encephalitis, bleeding diathesis & arthritis are rare
complications
Infection earlier in pregnancy has a higher
probability of affected infant



Sensorineural hearing loss (50-75%)
Cataracts and glaucoma (20-50%)
Cardiac malformations (20-50%)
Neurologic (10-20%)
Others to include growth retardation, bone
disease, HSM, thrombocytopenia, blueberry
muffin lesions
Rubella and the Fetus
Blueberry muffin spots representing
extramedullary hematopoesis
Purpura, Splenomegaly, jaundice,
meningoencephalitis, thrombocytopenia are
transient
Congenital cataracts, Glaucoma, heart disease,
deafness, microcephaly and mental
retardation are permanent abnormalities
Sequele: Diabetes, thyroid abnormalities,
precocious puberty & progressive
panencephalitis
Diagnosis
Maternal IgG may represent immunization or past
infection - Useless!
Can isolate virus from nasal secretions
Less frequently from throat, blood, urine, CSF
Serologic testing
IgM = recent postnatal or congenital infection
Rising monthly IgG titers suggest congenital infection
Diagnosis after 1 year of age difficult to establish
Prevention and Treatment
Vaccination (95% seroconversion)
@ 15 months and early adulthood
Immune status checking in teenagers, pre-
college and pre-pregnancy
Antenatal testing
Serology testing for presumed exposures
(paired Sera)
No in-utero therapy
Cytomegalovirus
DNA virus
Congenital infection - 1%
5-10% of those infected show clinical illness at
birth
Neonatal MR - 20-30%
90% of survivors get late complications
5-15% with no demonstrable disease at birth
get some abnormality (deafness)
Cytomegalovirus (CMV)
Most common congenital viral infection
~40,000 infants per year in the U.S.
Mild, self limiting illness
Transmission can occur with primary infection or
reactivation of virus
40% risk of transmission in primary infxn
Studies suggest increased risk of transmission
later in pregnancy
However, more severe sequalae associated with earlier
acquisition
Clinical Manifestations
90% are asymptomatic at birth!
Up to 15% develop symptoms later, notably
sensorineural hearing loss
Symptomatic infection
SGA, HSM, petechiae, jaundice, chorioretinitis,
periventricular calcifications, neurological
deficits
>80% develop long term complications
Hearing loss, vision impairment, developmental
delay
CMV Congenital Infection
Hepatomegaly }
Spleenomegaly }
Jaundice }TORCH
Thrombocytopenia }Syndrome
Petechiae }
Microcephaly }
Intrauterine growth retardation }
CMV Congenital Infection (Late)
Venticulomegaly
Cerebral atrophy
Mental retardation
Psychomotor delay
Seizures
Learning difficulties and language delay
Chorioretinitis / Optic atrophy
Intracranial calcifications
Long bone radiolucencies, dental abnormalities
Pneumonitis
Ventriculomegaly and
calcifications of
congenital CMV
Diagnosis
Maternal IgG shows only past infection
Infection common this is useless
Viral isolation from urine or saliva in 1
st
3weeks of
life
Afterwards may represent post-natal infection
Viral load and DNA copies can be assessed by PCR
Less useful for diagnosis, but helps in following viral
activity in patient
Serologies not helpful given high antibody in
population
Treatment
Ganciclovir 6wks in symptomatic infants
Studies show improvement or no progression of hearing
loss at 6mos
No other outcomes evaluated (development, etc.)
Neutropenia often leads to cessation of therapy
Treatment currently not recommended in
asymptomatic infants due to side effects
Area of active research to include use of
valgancyclovir, treating asymptomatic patients, etc.
No vaccination
Herpes Simplex (HSV)
HSV1 or HSV2
Primarily transmitted through infected
maternal genital tract
Rationale for C-section delivery prior to
membrane rupture
Primary infection with greater transmission
risk than reactivation

Clinical Manifestations
Most are asymptomatic at birth
3 patterns of ~ equal frequency with symptoms
between birth and 4wks:
Skin, eyes, mouth (SEM)
CNS disease
Disseminated disease (present earliest)
Initial manifestations very nonspecific with skin
lesions NOT necessarily present
Presentations of congenital HSV
Diagnosis
Culture of maternal lesions if present at delivery
Cultures in infant:
Skin lesions, oro/nasopharynx, eyes, urine, blood,
rectum/stool, CSF
CSF PCR
Serologies again not helpful given high prevalence of
HSV antibodies in population
Treatment
High dose acyclovir 60mg/kg/day divided
q8hrs
X21days for disseminated, CNS disease
X14days for SEM
Ocular involvement requires topical therapy as
well
Index of Suspicion
When do you think of TORCH infections?
IUGR infants
HSM
Thrombocytopenia
Unusual rash
Concerning maternal history
Classic findings of any specific infection
Conclusion
The main issues include
General principles
Infection and the fetal affects
Specific problems for the fetus with maternal
infections.
Congenital syndromes - main features
Which TORCH Infections Can Absolutely Be
Prevented?
Rubella

Syphilis