3. • You are taking care of a term newborn
You are taking care of a term newborn
male with birth weight/length <10
male with birth weight/length <10th
th
%ile.
%ile.
Physical exam is normal except for a
Physical exam is normal except for a
slightly enlarged liver span. A CBC is
slightly enlarged liver span. A CBC is
significant for low platelets.
significant for low platelets.
• What, if anything, do you worry about?
What, if anything, do you worry about?
• How do you proceed with a work-up?
How do you proceed with a work-up?
4. Index of Suspicion
Index of Suspicion
• When do you think of TORCH
When do you think of TORCH
infections?
infections?
• IUGR infants
IUGR infants
• HSM
HSM
• Thrombocytopenia
Thrombocytopenia
• Unusual rash
Unusual rash
• Concerning maternal history
Concerning maternal history
• “
“Classic” findings of any specific infection
Classic” findings of any specific infection
6. Diagnosing TORCH Infection
Diagnosing TORCH Infection
• Good maternal/prenatal history
Good maternal/prenatal history
• Remember most infections of concern are
Remember most infections of concern are
mild illnesses often unrecognized
mild illnesses often unrecognized
• Thorough exam of infant
Thorough exam of infant
• Directed labs/studies based on most
Directed labs/studies based on most
likely diagnosis…
likely diagnosis…
• Again, DO NOT USE TORCH TITERS!
Again, DO NOT USE TORCH TITERS!
7. Screening TORCH Infections
Screening TORCH Infections
• Retrospective study of 75/182 infants with IUGR who
Retrospective study of 75/182 infants with IUGR who
were screened for TORCH infections
were screened for TORCH infections
• 1/75 with clinical findings, 11/75 with abnl lab findings
1/75 with clinical findings, 11/75 with abnl lab findings
• All patients screened:
All patients screened:
• TORCH titers, urine CMV culture, head US
TORCH titers, urine CMV culture, head US
• Only 3 diagnosed with infection
Only 3 diagnosed with infection
• NONE by TORCH titer!!
NONE by TORCH titer!!
• Overall cost of all tests = $51,715
Overall cost of all tests = $51,715
• “
“Shotgun” screening approach NOT cost effective nor
Shotgun” screening approach NOT cost effective nor
particularly useful
particularly useful
• Diagnostic work-up should be logical and directed by
Diagnostic work-up should be logical and directed by
history/exam findings
history/exam findings
Khan, NA, Kazzi, SN. Yield and costs of screening growth-retarded infants for torch
8. Toxoplasmosis
Toxoplasmosis
• Caused by protozoan – Toxoplasma gondii
Caused by protozoan – Toxoplasma gondii
• Domestic cat is the definitive host with infections via:
Domestic cat is the definitive host with infections via:
• Ingestion of cysts (meats, garden products)
Ingestion of cysts (meats, garden products)
• Contact with oocysts in feces
Contact with oocysts in feces
• Much higher prevalence of infection in European
Much higher prevalence of infection in European
countries (ie France, Greece)
countries (ie France, Greece)
• Acute infection usually asymptomatic
Acute infection usually asymptomatic
• 1/3 risk of fetal infection with primary maternal
1/3 risk of fetal infection with primary maternal
infection in pregnancy
infection in pregnancy
• Infection rate higher with infxn in 3
Infection rate higher with infxn in 3rd
rd
trimester
trimester
• Fetal death higher with infxn in 1
Fetal death higher with infxn in 1st
st
trimester
trimester
9. Clinical Manifestations
Clinical Manifestations
• Most (70-90%) are asymptomatic at birth
Most (70-90%) are asymptomatic at birth
• Classic triad of symptoms:
Classic triad of symptoms:
• Chorioretinitis
Chorioretinitis
• Hydrocephalus
Hydrocephalus
• Intracranial calcifications
Intracranial calcifications
• Other symptoms include fever, rash, HSM,
Other symptoms include fever, rash, HSM,
microcephaly, seizures, jaundice,
microcephaly, seizures, jaundice,
thrombocytopenia, lymphadenopathy
thrombocytopenia, lymphadenopathy
• Initially asymptomatic infants are still at high risk of
Initially asymptomatic infants are still at high risk of
developing abnormalities, especially chorioretinitis
developing abnormalities, especially chorioretinitis
11. Diagnosis
Diagnosis
• Maternal IgG testing indicates past
Maternal IgG testing indicates past
infection (but when…?)
infection (but when…?)
• Can be isolated in culture from
Can be isolated in culture from
placenta, umbilical cord, infant serum
placenta, umbilical cord, infant serum
• PCR testing on WBC, CSF, placenta
PCR testing on WBC, CSF, placenta
• Not standardized
Not standardized
• Newborn serologies with IgM/IgA
Newborn serologies with IgM/IgA
12. Toxo Screening
Toxo Screening
• Prenatal testing with varied sensitivity
Prenatal testing with varied sensitivity
not useful for screening
not useful for screening
• Neonatal screening with IgM testing
Neonatal screening with IgM testing
implemented in some areas
implemented in some areas
• Identifies infected asymptomatic infants
Identifies infected asymptomatic infants
who may benefit from therapy
who may benefit from therapy
13. Prevention and Treatment
Prevention and Treatment
• Treatment for pregnant mothers diagnosed with acute toxo
Treatment for pregnant mothers diagnosed with acute toxo
• Spiramycin daily
Spiramycin daily
• Macrolide antibiotic
Macrolide antibiotic
• Small studies have shown this reduces likelihood of congenital
Small studies have shown this reduces likelihood of congenital
transmission (up to 50%)
transmission (up to 50%)
• If infant diagnosed prenatally, treat mom
If infant diagnosed prenatally, treat mom
• Spiramycin, pyrimethamine (anti-malarial, dihydrofolate reductase
Spiramycin, pyrimethamine (anti-malarial, dihydrofolate reductase
inhib), and sulfadiazine (sulfa antibiotic)
inhib), and sulfadiazine (sulfa antibiotic)
• Leucovorin rescue with pyrimethamine
Leucovorin rescue with pyrimethamine
• Symptomatic infants
Symptomatic infants
• Pyrimethamine (with leucovorin rescue) and sulfadiazine
Pyrimethamine (with leucovorin rescue) and sulfadiazine
• Treatment for 12 months total
Treatment for 12 months total
• Asymptomatic infants
Asymptomatic infants
• Course of same medications
Course of same medications
• Improved neurologic and developmental outcomes demonstrated
Improved neurologic and developmental outcomes demonstrated
(compared to untreated pts or those treated for only one month)
(compared to untreated pts or those treated for only one month)
14. Syphilis
Syphilis
• Treponema pallidum (spirochete)
Treponema pallidum (spirochete)
• Transmitted via sexual contact
Transmitted via sexual contact
• Placental transmission as early as 6wks
Placental transmission as early as 6wks
gestation
gestation
• Typically occurs during second half
Typically occurs during second half
• Mom with primary or secondary syphilis more
Mom with primary or secondary syphilis more
likely to transmit than latent disease
likely to transmit than latent disease
• Large decrease in congenital syphilis since
Large decrease in congenital syphilis since
late 1990s
late 1990s
• In 2002, only 11.2 cases/100,000 live births
In 2002, only 11.2 cases/100,000 live births
reported
reported
17. Congenital Syphilis
Congenital Syphilis
• 2/3 of affected live-born infants are
2/3 of affected live-born infants are
asymptomatic at birth
asymptomatic at birth
• Clinical symptoms split into early or late
Clinical symptoms split into early or late
(2 years is cutoff)
(2 years is cutoff)
• 3 major classifications:
3 major classifications:
• Fetal effects
Fetal effects
• Early effects
Early effects
• Late effects
Late effects
18. Clinical Manifestations
Clinical Manifestations
• Fetal:
Fetal:
• Stillbirth
Stillbirth
• Neonatal death
Neonatal death
• Hydrops fetalis
Hydrops fetalis
• Intrauterine death in 25%
Intrauterine death in 25%
• Perinatal mortality in 25-30% if
Perinatal mortality in 25-30% if
untreated
untreated
20. Periostitis of long bones
Periostitis of long bones
seen in neonatal syphilis
seen in neonatal syphilis
21. Clinical Manifestations
Clinical Manifestations
• Late congenital:
Late congenital:
• Frontal bossing
Frontal bossing
• Short maxilla
Short maxilla
• High palatal arch
High palatal arch
• Hutchinson teeth
Hutchinson teeth
• 8
8th
th
nerve deafness
nerve deafness
• Saddle nose
Saddle nose
• Perioral fissures
Perioral fissures
• Can be prevented with appropriate treatment
Can be prevented with appropriate treatment
22. Hutchinson teeth – late result of
Hutchinson teeth – late result of
congenital syphilis
congenital syphilis
23. Diagnosing Syphilis
Diagnosing Syphilis
(Not in Newborns)
(Not in Newborns)
• Available serologic testing
Available serologic testing
• RPR/VDRL: nontreponemal test
RPR/VDRL: nontreponemal test
• Sensitive but NOT specific
Sensitive but NOT specific
• Quantitative, so can follow to determine disease activity
Quantitative, so can follow to determine disease activity
and treatment response
and treatment response
• MHA-TP/FTA-ABS: specific treponemal test
MHA-TP/FTA-ABS: specific treponemal test
• Used for confirmatory testing
Used for confirmatory testing
• Qualitative, once positive always positive
Qualitative, once positive always positive
• RPR/VDRL screen in ALL pregnant women
RPR/VDRL screen in ALL pregnant women
early in pregnancy and at time of birth
early in pregnancy and at time of birth
• This is easily treated!!
This is easily treated!!
24. CDC Definition of Congenital
CDC Definition of Congenital
Syphilis
Syphilis
• Confirmed if T. pallidum identified in skin
Confirmed if T. pallidum identified in skin
lesions, placenta, umbilical cord, or at
lesions, placenta, umbilical cord, or at
autopsy
autopsy
• Presumptive diagnosis if any of:
Presumptive diagnosis if any of:
• Physical exam findings
Physical exam findings
• CSF findings (positive VDRL)
CSF findings (positive VDRL)
• Osteitis on long bone x-rays
Osteitis on long bone x-rays
• Funisitis (“barber shop pole” umbilical cord)
Funisitis (“barber shop pole” umbilical cord)
• RPR/VDRL >4 times maternal test
RPR/VDRL >4 times maternal test
• Positive IgM antibody
Positive IgM antibody
25. Diagnosing Congenital Syphilis
Diagnosing Congenital Syphilis
• IgG can represent maternal antibody,
IgG can represent maternal antibody,
not infant infection
not infant infection
• This is VERY intricate and often
This is VERY intricate and often
confusing
confusing
• Consult your RedBook (or peds ID folks)
Consult your RedBook (or peds ID folks)
when faced with this situation
when faced with this situation
26. Treatment
Treatment
• Penicillin G is THE drug of choice for ALL
Penicillin G is THE drug of choice for ALL
syphilis infections
syphilis infections
• Maternal treatment during pregnancy very
Maternal treatment during pregnancy very
effective (overall 98% success)
effective (overall 98% success)
• Treat newborn if:
Treat newborn if:
• They meet CDC diagnostic criteria
They meet CDC diagnostic criteria
• Mom was treated <4wks before delivery
Mom was treated <4wks before delivery
• Mom treated with non-PCN med
Mom treated with non-PCN med
• Maternal titers do not show adequate response
Maternal titers do not show adequate response
(less than 4-fold decline)
(less than 4-fold decline)
27. Rubella
Rubella
• Single-stranded RNA virus
Single-stranded RNA virus
• Vaccine-preventable disease
Vaccine-preventable disease
• No longer considered endemic in the U.S.
No longer considered endemic in the U.S.
• Mild, self-limiting illness
Mild, self-limiting illness
• Infection earlier in pregnancy has a
Infection earlier in pregnancy has a
higher probability of affected infant
higher probability of affected infant
31. Diagnosis
Diagnosis
• Maternal IgG may represent immunization or
Maternal IgG may represent immunization or
past infection - Useless!
past infection - Useless!
• Can isolate virus from nasal secretions
Can isolate virus from nasal secretions
• Less frequently from throat, blood, urine, CSF
Less frequently from throat, blood, urine, CSF
• Serologic testing
Serologic testing
• IgM = recent postnatal or congenital infection
IgM = recent postnatal or congenital infection
• Rising monthly IgG titers suggest congenital
Rising monthly IgG titers suggest congenital
infection
infection
• Diagnosis after 1 year of age difficult to
Diagnosis after 1 year of age difficult to
establish
establish
33. Cytomegalovirus (CMV)
Cytomegalovirus (CMV)
• Most common congenital viral infection
Most common congenital viral infection
• ~40,000 infants per year in the U.S.
~40,000 infants per year in the U.S.
• Mild, self limiting illness
Mild, self limiting illness
• Transmission can occur with primary infection
Transmission can occur with primary infection
or reactivation of virus
or reactivation of virus
• 40% risk of transmission in primary infxn
40% risk of transmission in primary infxn
• Studies suggest increased risk of
Studies suggest increased risk of
transmission later in pregnancy
transmission later in pregnancy
• However, more severe sequalae associated with
However, more severe sequalae associated with
earlier acquisition
earlier acquisition
34. Clinical Manifestations
Clinical Manifestations
• 90% are asymptomatic at birth!
90% are asymptomatic at birth!
• Up to 15% develop symptoms later,
Up to 15% develop symptoms later,
notably sensorineural hearing loss
notably sensorineural hearing loss
• Symptomatic infection
Symptomatic infection
• SGA, HSM, petechiae, jaundice,
SGA, HSM, petechiae, jaundice,
chorioretinitis,
chorioretinitis, periventricular calcifications
periventricular calcifications,
,
neurological deficits
neurological deficits
• >80% develop long term complications
>80% develop long term complications
• Hearing loss, vision impairment, developmental
Hearing loss, vision impairment, developmental
delay
delay
36. Diagnosis
Diagnosis
• Maternal IgG shows only past infection
Maternal IgG shows only past infection
• Infection common – this is useless
Infection common – this is useless
• Viral isolation from urine or saliva in 1
Viral isolation from urine or saliva in 1st
st
3weeks of life
3weeks of life
• Afterwards may represent post-natal infection
Afterwards may represent post-natal infection
• Viral load and DNA copies can be assessed
Viral load and DNA copies can be assessed
by PCR
by PCR
• Less useful for diagnosis, but helps in following
Less useful for diagnosis, but helps in following
viral activity in patient
viral activity in patient
• Serologies not helpful given high antibody in
Serologies not helpful given high antibody in
population
population
37. Treatment
Treatment
• Ganciclovir x6wks in symptomatic infants
Ganciclovir x6wks in symptomatic infants
• Studies show improvement or no progression of
Studies show improvement or no progression of
hearing loss at 6mos
hearing loss at 6mos
• No other outcomes evaluated (development, etc.)
No other outcomes evaluated (development, etc.)
• Neutropenia often leads to cessation of therapy
Neutropenia often leads to cessation of therapy
• Treatment currently not recommended in
Treatment currently not recommended in
asymptomatic infants due to side effects
asymptomatic infants due to side effects
• Area of active research to include use of
Area of active research to include use of
valgancyclovir, treating asx patients, etc.
valgancyclovir, treating asx patients, etc.
38. Herpes Simplex (HSV)
Herpes Simplex (HSV)
• HSV1 or HSV2
HSV1 or HSV2
• Primarily transmitted through infected
Primarily transmitted through infected
maternal genital tract
maternal genital tract
• Rationale for C-section delivery prior to
Rationale for C-section delivery prior to
membrane rupture
membrane rupture
• Primary infection with greater
Primary infection with greater
transmission risk than reactivation
transmission risk than reactivation
39. Clinical Manifestations
Clinical Manifestations
• Most are asymptomatic at birth
Most are asymptomatic at birth
• 3 patterns of ~ equal frequency with
3 patterns of ~ equal frequency with
symptoms between birth and 4wks:
symptoms between birth and 4wks:
• Skin, eyes, mouth (SEM)
Skin, eyes, mouth (SEM)
• CNS disease
CNS disease
• Disseminated disease (present earliest)
Disseminated disease (present earliest)
• Initial manifestations very nonspecific with
Initial manifestations very nonspecific with
skin lesions NOT necessarily present
skin lesions NOT necessarily present
41. Diagnosis
Diagnosis
• Culture of maternal lesions if present at
Culture of maternal lesions if present at
delivery
delivery
• Cultures in infant:
Cultures in infant:
• Skin lesions, oro/nasopharynx, eyes, urine, blood,
Skin lesions, oro/nasopharynx, eyes, urine, blood,
rectum/stool, CSF
rectum/stool, CSF
• CSF PCR
CSF PCR
• Serologies again not helpful given high
Serologies again not helpful given high
prevalence of HSV antibodies in population
prevalence of HSV antibodies in population
42. Treatment
Treatment
• High dose acyclovir 60mg/kg/day
High dose acyclovir 60mg/kg/day
divided q8hrs
divided q8hrs
• X21days for disseminated, CNS disease
X21days for disseminated, CNS disease
• X14days for SEM
X14days for SEM
• Ocular involvement requires topical
Ocular involvement requires topical
therapy as well
therapy as well
43. Which TORCH Infection Presents
Which TORCH Infection Presents
With…
With…
• Snuffles?
Snuffles?
• syphilis
syphilis
• Chorioretinitis, hydrocephalus, and
Chorioretinitis, hydrocephalus, and
intracranial calcifications?
intracranial calcifications?
• toxo
toxo
• Blueberry muffin lesions?
Blueberry muffin lesions?
• rubella
rubella
• Periventricular calcifications?
Periventricular calcifications?
• CMV
CMV
• No symptoms?
No symptoms?
• All of them
All of them
44. Which TORCH Infections Can
Which TORCH Infections Can
Absolutely Be Prevented?
Absolutely Be Prevented?
• Rubella
Rubella
• Syphilis
Syphilis
45. When Are TORCH Titers Helpful
When Are TORCH Titers Helpful
in Diagnosing Congenital
in Diagnosing Congenital
Infection?
Infection?
• NEVER!
NEVER!
• MEDICALPPTX.COM
