ob us in maternal infections - vanderbilt university … be id tifi didentified • falxfalx...
TRANSCRIPT
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Did the fetus catch it?Did the fetus catch it?
The role of ultrasound
Jacques S. Abramowicz, MDJacques S. Abramowicz, MDDepartment of Ob/Department of Ob/GynGyn and Fetal & and Fetal &
Neonatal Medicine CenterNeonatal Medicine CenterChicago, USAChicago, USA
in perinatal infections
DisclaimerDisclaimer
I have no conflict of interest with respect to any of the material presented in this lecture. I am on the Ob/Gyn Board of advisors of Philips Healthcare and Siemens. I will not discuss off‐label or unapproved uses of drugs or devices.
1. Mother has known infection1. Mother has known infection‐‐ did it did it affect the fetus in a "affect the fetus in a "sonographicallysonographicallyrecognizable“ way?recognizable“ way?
2. 2. SonographicSonographic fetal findingsfetal findings‐‐ were were they caused by transmission of they caused by transmission of maternal (possibly unrecognized) maternal (possibly unrecognized) infection ?infection ?
In utero infectionCongenital syndromeCongenital infection
Intrapartum infection
Post partum infection
Congenital syndromeCongenital syndrome
CMVCMVParvovirus B19Parvovirus B19RubellaRubellaRubellaRubellaVaricellaVaricella (Chickenpox) and Herpes Zoster(Chickenpox) and Herpes ZosterToxoplasmaToxoplasmaHIV (?)HIV (?)
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Congenital infectionCongenital infection
SyphilisSyphilisGBSGBSListeriosisListeriosisHSVHSVHIVHIV
Neonatal infectionNeonatal infection
GBSGBSHepHep BBHepHep CCGonorrheaGonorrheaCondylomataCondylomata AcuminataAcuminataChlamydia Chlamydia trachomatistrachomatisCandidaCandidaHIVHIV
. Most infected fetuses will be sonographically normal. Ultrasound findings may change with ti
LimitationsLimitations
time. No strong correlation with neonatal outcome
Mother has diagnosed infection, did Mother has diagnosed infection, did the fetus catch it?the fetus catch it?the fetus catch it?the fetus catch it?
Did the fetus catch it?Did the fetus catch it?
DiagnosisDiagnosis
1. Direct: PUBS (Amniocentesis)1. Direct: PUBS (Amniocentesis)( )( )
2. Indirect: 2. Indirect: sonographicsonographic findingsfindings
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In In uteroutero infectioninfection
Congenital syndromesCongenital syndromesCongenital syndromesCongenital syndromesCMVCMV**
*Cytomegalovirus
CMVCMV
. Double stranded DNA herpes virus. Double stranded DNA herpes virus
. Emerged in recent years as the . Emerged in recent years as the most most importantimportant cause of congenital cause of congenital pp gginfection in the developed worldinfection in the developed world. Approximately . Approximately 1%1% (range, 0.5(range, 0.5‐‐2.5%) 2.5%) of all newborns are congenitally of all newborns are congenitally infected with CMVinfected with CMV
CMVCMV
. Route of congenital infection: . Route of congenital infection: presumably presumably transplacentaltransplacental. . . May also be transmitted . May also be transmitted perinatallyperinatally(aspiration of (aspiration of cervicovaginalcervicovaginal secretions in secretions in the birth canal and/or breastfeeding).the birth canal and/or breastfeeding).. . More than 50% More than 50% of infants fed with of infants fed with breast milk that contains infectious virus breast milk that contains infectious virus become infected with CMVbecome infected with CMV
CMVCMV. Approximately 10% of congenital CMV occur in women with primary infection during pregnancy, and 90% of these infants have neurological sequelae. P i i i i ( l. Preexisting immunity (eg, maternal recurrent infection) protects against severe disease, but sequelae in approximately 15% of these infants, particularly sensorineural hearing loss.
. Most common congenital infection (1% of . Most common congenital infection (1% of live births)live births). 10% of infected neonates demonstrate . 10% of infected neonates demonstrate clinical manifestations that could be clinical manifestations that could be
CMVCMV
identified, theoretically, by prenatal identified, theoretically, by prenatal ultrasoundultrasoundVentriculomegalyVentriculomegaly, intracranial calcifications, , intracranial calcifications, IUGR, IUGR, oligohydramniosoligohydramnios
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CMVCMV
ChaouiChaoui et al.:et al.: Marked Marked splenomegalysplenomegaly in fetal in fetal CMVCMV infection:infection: detection supported by 3detection supported by 3‐‐DD power power Doppler ultrasound. UOG 2002;20:299Doppler ultrasound. UOG 2002;20:299‐‐302302
Parvovirus infectionParvovirus infection
B19B19NonNon‐‐immune immune hydropshydrops(NIH)(NIH)
. Most infected fetuses are . Most infected fetuses are sonographicallysonographicallynormalnormal. Findings may change with time. Findings may change with time
di l i i h i fdi l i i h i f
ParvovirusParvovirus
. No direct correlation with infant outcome. No direct correlation with infant outcome
Parvovirus infectionParvovirus infection
Indirect evidence:Fetal anemia
PUBSMCA Doppler (PSV)
Sens: 94%Spec: 93%PPV: 94%NPV: 93%
(Cosmi et al. AJOG, 2002;187:1290‐3)
RubellaRubella
. Single. Single‐‐stranded RNA virus of the stranded RNA virus of the togavirustogavirus family family
. Mild . Mild exanthematousexanthematous disease of childhooddisease of childhood
. In pregnant host, can have catastrophic effects . In pregnant host, can have catastrophic effects on fetus (first described by Gregg in 1941). on fetus (first described by Gregg in 1941). . Last epidemic in . Last epidemic in prevaccineprevaccine era (1964era (1964‐‐1965): 1965): approx. 11,000 miscarriages, approx. 11,000 miscarriages, abortions,stillbirthsabortions,stillbirths, , and approx. 20,000 cases of congenital rubellaand approx. 20,000 cases of congenital rubellasyndrome in newbornsyndrome in newbornss
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RUBELLARUBELLA
•• Incidence: < Incidence: < 1:100,000 live 1:100,000 live birthsbirths
•• Prenatal diagnosis by Prenatal diagnosis by sonographicsonographicfindings findings never reportednever reported
i l d di l d d b li ib li i•• Potential detected Potential detected abnormalities: abnormalities: cardiac anomalies, cardiac anomalies, microcephalymicrocephaly, , hepatosplenomegalyhepatosplenomegaly, , IUGR, cataract, IUGR, cataract, microphtalmiamicrophtalmia
VaricellaVaricella and Herpes Zosterand Herpes Zoster
VaricellaVaricella and Herpes Zosterand Herpes Zoster. Incidence: 0.7/1000 pregnancies Incidence: 0.7/1000 pregnancies . Infection until 28 weeks can lead to . Infection until 28 weeks can lead to intrauterine infection intrauterine infection . 1. 1‐‐2% risk of developing congenital 2% risk of developing congenital varicellavaricellasyndrome (CVS): syndrome (CVS): 1.1. virusvirus‐‐specific deformation specific deformation sequence:limbsequence:limb
hypoplasiahypoplasia, skin scarring, , skin scarring, microcephalymicrocephaly, , microophthalmiamicroophthalmia, cataract, , cataract, cerebellarcerebellardysplasia, GI or/and GU malformations.dysplasia, GI or/and GU malformations.
2.2. Non specific NIHNon specific NIH‐‐like syndromelike syndrome
VaricellaVaricella and Herpes Zosterand Herpes Zoster
Most common reported ultrasound finding: Most common reported ultrasound finding: polyhydramniospolyhydramniosAlso reported:Also reported: intrahepaticintrahepatic calcificationscalcifications
Petignat et al.: Fetal varicella‐herpes zoster syndrome in early pregnancy: ultrasonographic and morphological correlation. Prenat Diag. 2001;21:121‐4
Also reported: Also reported: intrahepaticintrahepatic calcifications, calcifications, hepatomegalyhepatomegaly, , hydropshydrops, limb malformations, , limb malformations, ventriculomegalyventriculomegaly, IUGR, IUGR
ToxoplasmaToxoplasma ToxoplasmaToxoplasma
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ToxoplasmosisToxoplasmosis ToxoplasmosisToxoplasmosis
Infection: Infection: 1.1.Contact with cat feces (gardening or cleaning Contact with cat feces (gardening or cleaning litter box). litter box).
2.2.Eating contaminated food (lamb, pork and Eating contaminated food (lamb, pork and ))venison). venison).
3.3.Unpasteurized dairy products and even water can Unpasteurized dairy products and even water can also become contaminated.also become contaminated.
4.4. Unwashed produce and not properly cleaned Unwashed produce and not properly cleaned utensils or cutting boards.utensils or cutting boards.
5.5.Very rare cases, may be acquired through organ Very rare cases, may be acquired through organ transplant or blood transfusion.transplant or blood transfusion.
ToxoplasmosisToxoplasmosisIncidence of congenital toxoplasmosis: 1/1000Incidence of congenital toxoplasmosis: 1/1000‐‐1/10 000 live births. 50% of 1/10 000 live births. 50% of fetuses infected, 1/3 sub clinical infection, 1/10 severe infection.Risk of congenital toxoplasmosis: lower ifRisk of congenital toxoplasmosis: lower ifRisk of congenital toxoplasmosis: lower if Risk of congenital toxoplasmosis: lower if infection occurs during the infection occurs during the first trimester (10% first trimester (10% to 25%)to 25%) than during the than during the third trimester (60% to third trimester (60% to 90%).90%).But severity of congenital infection is But severity of congenital infection is substantially substantially higherhigher if infection occurs during if infection occurs during the the first trimesterfirst trimester..
ToxoplasmosisToxoplasmosis
. . Typical triad: hydrocephalus, Typical triad: hydrocephalus, chorioretinitischorioretinitis, , and intracranial calcifications. Does not and intracranial calcifications. Does not always occur. always occur. HepatosplenomegalyHepatosplenomegaly thrombocytopeniathrombocytopenia. . HepatosplenomegalyHepatosplenomegaly, thrombocytopenia, , thrombocytopenia, microcephalymicrocephaly, convulsions, fever, and SGA , convulsions, fever, and SGA . Most neonates: asymptomatic at birth on . Most neonates: asymptomatic at birth on routine examination but deafness, mental routine examination but deafness, mental delay, learning difficulties often detected delay, learning difficulties often detected later in life.later in life.
TOXOPLASMOSISTOXOPLASMOSIS
• Ventriculomegaly most frequently documented finding
• Intracranial calcifications, placentomegaly liver calcifications andplacentomegaly, liver calcifications and ascites
• hyperechoic bowel have been reported
• microcephaly never been reported in utero
HIVHIV
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HIVHIV++ mothermother.. DysmorphicDysmorphic syndrome in children syndrome in children exposed to HIV in exposed to HIV in uteroutero: IUGR (75%), : IUGR (75%), microcephalymicrocephaly (70%), and craniofacial (70%), and craniofacial abnormalities [abnormalities [hypertelorismhypertelorism (50%), (50%),
prominent forehead prominent forehead (75%), (75%), flat nasal bridge flat nasal bridge (70%), (70%), obliquity of the eyes obliquity of the eyes (65%), (65%), long long palpebralpalpebral fissures fissures (60%), (60%), short nose short nose (65%), (65%),
and patulous lips and patulous lips (60%)](60%)]
Marion et al., 1986‐87
HIVHIV++ mothermother
Confounding factors: ethnicity, poor Confounding factors: ethnicity, poor nutrition, substance abuse and nutrition, substance abuse and concomitant infections. concomitant infections.
.. Reduced left ventricular size (but no Reduced left ventricular size (but no altered function)altered function). Shorter femurs. Shorter femurs
Hornberger et al. Am Heart J, 2000;140:575‐84
In In uteroutero infectioninfection
Congenital infectionCongenital infectionCongenital infectionCongenital infection
SyphilisSyphilisTreponema pallidum
Nearly half of all fetuses infected withNearly half of all fetuses infected withNearly half of all fetuses infected with Nearly half of all fetuses infected with syphilis die shortly before or after birth.syphilis die shortly before or after birth.
SYPHILIS
•• Most frequent Most frequent sonographicsonographic manifestations: manifestations: hepatomegalyhepatomegaly, , placentomegalyplacentomegaly
•• Less common: Less common: ascitesascites, , hydropshydrops and and polyhydramniospolyhydramnios
•• Resolution of Resolution of sonographicsonographic signs signs reported reported with maternal with maternal therapytherapy
Group B Group B StreptococcusStreptococcus (GBS)(GBS)
GBS: most common cause of lifeGBS: most common cause of life‐‐threatening infections in newbornsthreatening infections in newbornsMaternal infection at conception or Maternal infection at conception or within the first two weeks of pregnancywithin the first two weeks of pregnancywithin the first two weeks of pregnancy within the first two weeks of pregnancy may lead tomay lead to. Hearing loss. Hearing loss. Vision loss. Vision loss. Mental delay. Mental delay
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ListeriosisListeriosis ListeriosisListeriosis
Listeria monocytogenes: gram‐positive, motile bacillus with aerobic and facultative anaerobic characteristics. Found in soil and water and can b i d b i l th t d t illbe carried by animals that do not appear ill, leading to contamination of food of animal origin, particularly ready‐to‐eat foods such as meats and dairy products. Other potential sources: unpasteurized raw milks or foods
ListeriosisListeriosis ListeriosisListeriosis
Placental transfer: can cause Placental transfer: can cause amnionitisamnionitis, , resulting in spontaneous septic abortion or resulting in spontaneous septic abortion or PTL with delivery of infected baby. PTL with delivery of infected baby. F t l i f ti if t ti iF t l i f ti if t ti iFetal infection may manifest as septicemia, Fetal infection may manifest as septicemia, meningoencephalitismeningoencephalitis, or disseminated , or disseminated granulomatousgranulomatous lesions with lesions with microabscessesmicroabscesses. . TwentyTwenty‐‐two percent of two percent of perinatalperinatal infections infections result in neonatal death or stillbirthresult in neonatal death or stillbirth
Herpes simplex (HSV)Herpes simplex (HSV) Herpes simplex (HSV)Herpes simplex (HSV)
. Congenital infection: often severe, high morbidity . Congenital infection: often severe, high morbidity and mortality. and mortality. . Most cases acquired during delivery. Most cases acquired during delivery. Intrauterine infection: . Intrauterine infection: transplacentaltransplacental passage or passage or ascending local infectionascending local infectionascending, local infection. ascending, local infection. . . TransplacentalTransplacental infection may result in a neonate infection may result in a neonate born with skin lesions, multisystem organ failure born with skin lesions, multisystem organ failure and CNS lesions consistent with destruction of and CNS lesions consistent with destruction of developing brain tissue (developing brain tissue (microcephalymicrocephaly, , hydranencephalyhydranencephaly, , multicysticmulticystic encephalomalaciaencephalomalacia), ), as well as as well as microophthalmiamicroophthalmia, , chorioretinitischorioretinitis, , NIHNIH
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HSVHSV HSVHSV• 100 reported cases of intrauterine infections resulting in clinical signs
• Only sonographic sign reported antenatally: hydranencephalyy y p y
• Potentially detectable: microcephaly, intracranial calcifications, IUGR
SonographicSonographic findings: a sign of findings: a sign of intrauterine infection?intrauterine infection?
Sonographic findings are present‐g p g pso what?
VentriculomegalyVentriculomegaly
•• Measured at the posterior aspect of the Measured at the posterior aspect of the choroid choroid plexus (atrium)plexus (atrium)
•• Almost always symmetricAlmost always symmetric
l bl b % f b ib d% f b ib d•• Only about 5Only about 5% of cases can be attributed % of cases can be attributed to fetal infectionto fetal infection
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Intracranial CalcificationsIntracranial Calcifications
• Rare: 1010‐‐15% of affected, scanned fetuses15% of affected, scanned fetuses
• Main cause: Intrauterine infection
• Hallmark: periventricular hyperechoic foci
• May also be located in the thalami and basal ganglia
• Small with no acoustic shadowing
• Most frequent etiology: CMV and Toxoplasmosis (also Rubella and Tri 13)
HHydranencephalyydranencephaly•• Most Most severe (endsevere (end‐‐stage) stage) manifestation of manifestation of destructive destructive processprocess
•• Cerebral hemispheres replaced by Cerebral hemispheres replaced by fluidfluid•• Brain Brain stem stem preserved, preserved, posterior posterior fossafossa structures structures
bb id tifi did tifi dcan be can be identifiedidentified•• FalxFalx present, absent or deviatedpresent, absent or deviated•• Think: Think: CMV, Toxoplasmosis, Herpes simplex, CMV, Toxoplasmosis, Herpes simplex, RubellaRubella
•• (Tri 13, (Tri 13, neoplasmsneoplasms, bleeding disorders, , bleeding disorders, syndromes) syndromes)
MicrocephalyMicrocephaly MicrocephalyMicrocephaly
• Rarely isolated. Often associated with other CNS anomalies
• Diagnosis: HC >3SD below mean for• Diagnosis: HC >3SD below mean for GA
• Abnormal HC/AC and HC/FL ratios
• Isolated microcephaly: documented in CMV, Rubella and Herpes simplex
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Cardiac Cardiac anomaliesanomalies
• Cardiomegaly: mostly in CMV
(Check cardiothoracic ratio)
• VSD, ASD, Pulmonic stenosis and , ,coaractation of the aorta: Rubella
HepatosplenomegalyHepatosplenomegaly
• Documented in all TORCH infections
• Often transient finding
• Nomograms are availableNomograms are available
IntraIntra‐‐abdominal Calcificationsabdominal Calcifications
•• Typical appearance: Typical appearance: echogenicechogenic foci foci withwith acoustic shadowingacoustic shadowing
•• Peritoneum, intestinal lumen, organ Peritoneum, intestinal lumen, organ parenchyma, parenchyma, biliarybiliary tree and vascular tree and vascular structuresstructures
•• DiiferentDiiferent from from echogenicechogenic bowelsbowels
•• Think: Think: CMV CMV and Toxoplasmosisand Toxoplasmosis
HydropsHydrops, Placenta and , Placenta and Amniotic fluidAmniotic fluid
•• HydropsHydrops reported in most TORCH but reported in most TORCH but may be transientmay be transient
•• PlacentomegalyPlacentomegaly: : usually associated with usually associated with intrauterine infection, but small intrauterine infection, but small placentaeplacentae have also been reportedhave also been reported
•• HydramniosHydramnios and and oligohydramniosoligohydramnios have have been reported with similar frequencybeen reported with similar frequency
Fetal growth restrictionFetal growth restriction
• EFW< 10th percentile
• Common feature in early infection with almost any infection (Syphylis in particular)
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ControversiesControversies
InfluenzaInfluenzaMeaslesMeaslesMumpsMumpsEchovirusesEchovirusesCoxsakieCoxsakie virusesviruses
Major (common) Major (common) sonographicsonographic findingsfindings
IUGRIUGRVentriculomegalyVentriculomegalyHydropsHydropsHydropsHydrops
Intracranial calcificationsIntracranial calcificationsIntraabdominalIntraabdominal calcificationscalcificationsEchogenicEchogenic bowelsbowels
Less commonLess common
•• HepatosplenomegalyHepatosplenomegaly••Cardiac anomaliesCardiac anomalies••HydranencephalyHydranencephaly••MicrocephalyMicrocephaly
IUGRIUGR
Common in: . CMV. Rubella. HSV.Varicella
VentriculomegalyVentriculomegaly
5% of cases can be attributed5% of cases can be attributedto fetal infectionto fetal infection
Intracranial calcificationsIntracranial calcifications
CMV
ToxoplasmosisRubellaRubellaHSV
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NIHNIH
MechanismsCardiovascular failureChromosomal anomaliesF t l iFetal anemiaChest compressionTwinning
NIHNIH
Infectious etiologyInfectious etiologyCMVCMVParvovirus B19Parvovirus B19ToxoplasmosisToxoplasmosisSyphilisSyphilisHSVHSVRubellaRubellaCoxsackievirusCoxsackievirusVaricellaVaricellaRespiratory Respiratory syncitialsyncitial virusvirus
NIHNIH
Possible mechanisms in infections:Possible mechanisms in infections:. Fetal anemia, myocarditis, hepatitis. Fetal anemia, myocarditis, hepatitis. May be transient. May be transient. . PlacentomegalyPlacentomegaly may be early or may be early or only signonly sign
IntraIntra‐‐abdominal (hepatic) abdominal (hepatic) calcificationscalcifications
EchogenicEchogenic focusefocuse withwith acoustic shadowingacoustic shadowing. Peritoneal (. Peritoneal (meconiummeconium peritonitis)peritonitis)(( p )p ). . ParenchymalParenchymal ((infectioninfection, tumor), tumor). Vascular (calcified portal or venous clots). Vascular (calcified portal or venous clots)
IntrahepaticIntrahepatic calcificationscalcifications
HSVHSVVaricellaVaricella‐‐ZosterZosterRubellaRubellaRubellaRubellaCMVCMVEchovirus 11Echovirus 11SyphilisSyphilisToxoplasmosisToxoplasmosis
EchogenicEchogenic bowelsbowels
Definition: bowels as Definition: bowels as echogenicechogenicas bone (decrease overall gain to as bone (decrease overall gain to check)check)
CMVCMVToxoplasmosisToxoplasmosis
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EchogenicEchogenic bowelsbowels
Severe malformations : 9%Severe malformations : 9%MultifetalMultifetal pregnancy: 9%pregnancy: 9%Bowel obstruction: 6%Bowel obstruction: 6%Abnormal Abnormal karyotypekaryotype: 6%: 6%Intrauterine infection: 6%Intrauterine infection: 6%CF: 2.5%CF: 2.5%Unknown: 38%Unknown: 38%
YaronYaron et al. Fetal et al. Fetal DiagDiag TherTher, 1999;14:176, 1999;14:176‐‐80. n=7980. n=79
PearlsPearls
• Ultrasound is not a sensitive test for fetal infection
• Normal sonographic fetal anatomy does not predict favorable outcome
• Multiple organ systems affected in 50% of cases
VentriculomegalyVentriculomegaly, intracranial and hepatic , intracranial and hepatic calcifications:calcifications:
CMVCMV
PearlsPearls
Ocular and cardiac anomalies: Ocular and cardiac anomalies: Congenital rubella syndromeCongenital rubella syndrome
Limb contractures and cerebral anomalies:Limb contractures and cerebral anomalies:VaricellaVaricella zoster viruszoster virus
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