Transplacental Hematologic Infections

Slide 1 · Transplacental (Hematologic) Infections

Maternal bloodstream → placenta → fetal organs

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Distinguish hematogenous transplacental spread from ascending perinatal infection.

Relate gestational timing and organism to fetal injury patterns.

Explain parvovirus B19–related erythroid aplasia and nonimmune hydrops.

Recognize selected Robbins-described congenital infection syndromes and morphologic clues.

The focus is route, fetal pathology, and clinicopathologic interpretation.

Slide 3 · Two dominant routes of fetal acquisition

Ascending (transcervical)

Organisms move from the cervicovaginal tract; Fetal exposure may occur before or during delivery.

Transplacental (hematogenous)

Maternal bloodborne organisms cross via chorionic villi and enter the fetal bloodstream.

The pathways can coexist, but neither requires passage through the other.

Slide 4 · “Hematologic” describes the route—not the phenotype

Maternal bloodstream provides access to chorionic villi and ultimately fetal blood.

Some infections injure the fetal hematopoietic system; Many primarily involve other organs.

A transplacental infection may present with neurologic, ocular, hepatic, cardiac, or systemic findings.

Do not equate transplacental transmission with hemolytic disease.

Slide 5 · Transplacental access through the chorionic villi

Maternal compartment

Bloodborne organism in maternal circulation

Chorionic villi

Placental interface transversed by infection

Fetal compartment

Dissemination via fetal circulation

Schematic: Bloodborne spread can occur throughout gestation.

Slide 6 · Ascending versus transplacental infection

Ascending (transcervical)

Transplacental (hematogenous)

Microorganisms ascend from the cervix or vagina.

Organisms disseminate through maternal blood and chorionic villi.

Inhalation of infected amniotic fluid or birth-canal exposure.

Fetal bloodstream is directly exposed after crossing the placental interface.

Pneumonia, sepsis, meningitis may follow.

Pattern depends strongly on fetal age and organism.

Route of acquisition influences, but does not determine, clinical presentation.

Slide 7 · Mixed pathways can occur

Ascending organism reaches endometrium

Infection extends to chorionic villi

Fetal blood is secondarily invaded

The source explicitly describes acquisition through both routes in some cases.

Route attribution may be difficult when placental inflammation and fetal infection coexist.

Slide 8 · Organisms transmitted hematogenously

Parasitic

Toxoplasma and malaria are textbook examples.

Viral

Many viral pathogens can cross the placenta; Parvovirus B19 is highlighted.

Bacterial

Listeria and Treponema are notable examples, despite most bacteria favoring ascending spread.

The examples illustrate categories; This is not an exhaustive organism list.

Slide 9 · Two determinants of fetal phenotype

Gestational timing

The stage of fetal development changes vulnerability and the type of long-term injury.

Microorganism

Cell tropism, tissue distribution and pathogenesis shape the distinctive organ lesions.

Together, timing and pathogen determine clinical and morphologic expression.

Slide 10 · Gestation changes the consequences of infection

Earlier exposure

Risk of persistent developmental consequences.

During gestation

Bloodstream spread may occur at any stage.

Near delivery

Selected infections may also transmit through maternal–fetal blood exchange.

An early insult can have effects that are not clinically obvious until childhood.

Slide 11 · Transmission can also occur during delivery

Transplacental hematogenous spread is not confined to a single trimester.

Hepatitis B and HIV are examples of organisms that may be acquired through maternal-to-fetal transfusion during delivery.

An infection detected neonatally is not, by itself, proof of prenatal acquisition.

Separate the time of detection from the time and route of transmission.

Slide 12 · Infection is not synonymous with clinical disease

Evidence of infection

Manifest disease or sequelae

Organism reaches and infects fetal or neonatal tissues.

Inflammatory, destructive, or developmental injury becomes evident.

Some infected infants remain asymptomatic initially.

Clinical expression may be immediate or delayed.

Transmission route may be known or uncertain.

Severity varies with agent and gestational age.

Slide 13 · TORCH: A clinical-pathologic grouping

T — Toxoplasmosis

A parasitic congenital infection with ocular and neurologic consequences.

O — Other infections

Includes organisms such as congenital syphilis.

R — Rubella

Included in the source definition of TORCH.

C — Cytomegalovirus

A congenital viral infection with multisystem manifestations.

H — Herpesviruses

Included in TORCH; Route of acquisition may also be ascending.

TORCH is a syndrome-oriented mnemonic, not a single pathogen or transmission mechanism.

Slide 14 · Overlapping manifestations in the TORCH group

Organ system

Examples in Robbins

Systemic

Fever

Central nervous system

Encephalitis

Eye

Chorioretinitis

Liver / spleen

Hepatosplenomegaly

Heart / lung

Myocarditis or pneumonitis

Hematologic / skin

Hemolytic anemia; vesicular or hemorrhagic lesions

Overlapping syndromes demand agent-specific interpretation and confirmation.

Slide 15 · Neurologic involvement can dominate the phenotype

Encephalitis is one of the shared presentations explicitly listed for TORCH infections.

Neurologic impairment after intrauterine infection may be delayed rather than evident at birth.

Congenital CMV and toxoplasmosis have additional source-described central nervous system findings.

Neurologic findings are clinically important, but not pathogen-specific.

Slide 16 · Ocular disease: Chorioretinitis and its context

Chorioretinitis occurs among the shared TORCH presentations.

Congenital toxoplasmosis can produce chorioretinitis together with cerebral abnormalities.

Ocular findings should be interpreted together with neurologic, systemic, and laboratory evidence.

The anatomical site of ocular injury provides a clue—not a unique diagnosis.

Slide 17 · Visceral manifestations of congenital infection

Hepatosplenomegaly

Part of the shared TORCH phenotype; Also described in congenital CMV.

Pneumonitis

Included among overlapping TORCH manifestations.

Myocarditis

Can occur in the multisystem TORCH syndrome.

Encephalitis

May coexist with visceral disease and systemic illness.

Slide 18 · Why hematologic findings matter

The TORCH clinical-pathologic group can include hemolytic anemia.

Congenital CMV can present with anemia and bleeding from thrombocytopenia.

Parvovirus B19 instead preferentially damages erythroid progenitors and may cause red cell aplasia.

Anemia from destruction and anemia from impaired production are mechanistically different.

Slide 19 · Skin clues in congenital infections

Vesicular lesions

Included among possible TORCH manifestations.

Hemorrhagic lesions

Included among TORCH presentations and can signal multisystem involvement.

Listerial papules

Red papular rash of extremities described in neonatal listeriosis.

Congenital syphilis

Desquamating or bullous eruption, often involving palms and soles.

Skin patterns are clues to investigate, not standalone confirmation.

Slide 20 · Early gestational infection: Lasting consequences

Early infection

Disturbance while organs are developing.

Fetal effect

Growth restriction or congenital organ abnormalities.

Later recognition

Intellectual disability and other long-term impairments.

Cataracts, cardiac defects, and bone defects among possible long-term consequences.

Slide 21 · Congenital sequelae

Domain

Examples of long-term consequence

Growth

Growth retardation

Neurodevelopment

Intellectual disability

Ocular

Cataracts

Cardiovascular

Congenital cardiac anomalies

Skeletal

Bone defects

These findings are collective TORCH possibilities; They are not universal for each agent.

Slide 22 · Congenital infections within the FGR differential

Intrauterine infection

Reduced intrinsic fetal growth potential

Fetal growth restriction

Congenital infection among fetal causes of small-for-gestational-age infants.

The TORCH group is specifically highlighted among infections associated with FGR.

Slide 23 · FGR etiologies: Avoid prematurely assuming infection

Fetal causes

Alternative maternal / placental causes

Congenital infections

Reduced placental blood flow in maternal vascular disease

Chromosomal abnormalities

Placental vascular disorders or thrombosis

Congenital anomalies

Maternal malnutrition or exposures

Growth restriction alone cannot establish a congenital infection.

Slide 24 · The meaning of symmetric growth restriction

Fetal-factor growth restriction as often symmetric or proportionate.

In symmetric FGR, multiple organ systems are similarly affected.

Congenital infection belongs in the fetal-factor differential alongside chromosomal disease and congenital anomalies.

Symmetry supports a broad fetal-growth assessment; It does not identify a specific pathogen.

Slide 25 · Pattern recognition has limits

Shared phenotype

Hepatosplenomegaly, skin lesions, anemia, and neurologic injury may occur with more than one agent.

Different mechanisms

Aplastic erythropoiesis differs from hemolysis or thrombocytopenia.

Timing matters

A delayed clinical finding may originate from infection in utero.

Integrate organism, timing, clinical pattern and corroborating tests.

Slide 26 · Parvovirus B19: The hematopoietic prototype

B19 causes erythema infectiosum (“fifth disease”) in immunocompetent older children.

In the fetus, its distinctive pathology is preferential infection of erythroid precursor cells.

Consequent failure of red cell production can contribute to severe fetal anemia and hydrops.

Slide 27 · Parvovirus B19 infection during pregnancy

Population / outcome

Robbins statement

Nonimmune pregnant females

Approximately 1–5% acquire B19 infection.

Overall prognosis

Vast majority of affected pregnancies have normal outcomes.

Adverse outcome

Spontaneous abortion, especially in the second trimester.

Other adverse outcomes

Stillbirth, nonimmune hydrops or congenital anemia.

The 1–5% figure refers to infection of seronegative pregnant females, not to fetal loss.

Slide 28 · Possible fetal outcomes after maternal B19 infection

Normal outcome

Most pregnancies after maternal infection remain uncomplicated.

Pregnancy loss

Spontaneous abortion or stillbirth in a minority of affected pregnancies.

Hematologic illness

Congenital anemia and potentially nonimmune hydrops fetalis.

Do not interpret maternal B19 infection as inevitable fetal injury.

Slide 29 · Why B19 targets fetal erythropoiesis

Preference for erythroid precursors

Viral replication within normoblasts

Apoptosis of red cell progenitors

The adjacent fetal-hydrops section specifically identifies progenitor apoptosis.

Loss of the precursor population causes red cell aplasia.

Slide 30 · Red cell aplasia: The key mechanistic lesion

Erythroid progenitor destruction

Reduced fetal erythrocyte output

Congenital anemia in severe cases

The major lesion is impaired cell production, not primarily immune red cell hemolysis.

The degree of fetal compromise depends on how severe the anemia becomes.

Slide 31 · Two mechanisms that produce fetal anemia

Reduced production: B19

Increased destruction: Immune hemolysis

Viral injury to erythroid precursors.

Maternal antibodies react with fetal red cell antigens.

Red cell aplasia is a central mechanism.

Peripheral red cell destruction is the central mechanism.

May lead to nonimmune hydrops.

May lead to immune hydrops and neonatal jaundice.

Both may culminate in anemia-associated hydrops despite different initiating lesions.

Slide 32 · Parvovirus B19: An anemia-to-hydrops pathway

B19 replication in erythroid precursors

Erythroid cell loss and red cell aplasia

Severe fetal anemia in affected cases

Cardiovascular compromise → fetal fluid accumulation

Mechanistic integration; Not every fetal B19 infection causes anemia or hydrops.

Slide 33 · Hydrops fetalis: Recognize the morphologic endpoint

Fetal hydrops describes abnormal accumulation of edema fluid during intrauterine life.

The most generalized form is severe widespread fetal edema (hydrops fetalis).

Fluid may also collect in pleural or peritoneal spaces or postnuchal soft tissues.

Hydrops is a phenotype with multiple causes—not a diagnosis of viral infection.

Slide 34 · Causes of nonimmune hydrops in the source

Cardiovascular

Structural defects and arrhythmias can cause fetal heart failure.

Chromosomal

Selected aneuploidies and Turner syndrome may be associated.

Fetal anemia

Alpha-thalassemia and parvovirus B19 are named examples.

Other

Twin-to-twin transfusion and unexplained cases also occur.

Parvovirus B19 belongs within, not outside, the broader differential.

Slide 35 · Parvovirus B19: Identifying erythroid inclusions

Infected erythroid precursor

Uninfected precursor for comparison

Schematic only—not an H&E specimen. Fig. 10.9, inclusions are large and homogeneous, with a peripheral chromatin rim.

Slide 36 · Inclusion bodies: B19 versus CMV

Parvovirus B19

Cytomegalovirus

Early erythroid precursors / normoblasts.

Enlarged infected cells across many tissues.

Large, homogeneous intranuclear inclusion.

Large basophilic intranuclear inclusion with a clear halo.

Rim of residual peripheral chromatin.

“Owl’s eye” nuclear appearance; Cytoplasmic inclusions can occur.

These descriptions are morphological principles, not a substitute for genuine stained material.

Slide 37 · Case: Fetal anemia following maternal viral illness

A pregnancy is complicated by maternal viral infection. Subsequent assessment suggests severe fetal anemia and generalized fluid accumulation. Erythroid precursors contain large homogeneous intranuclear inclusions.

1. Which infection best fits the hematopoietic morphology?

2. What mechanism connects the infection to hydrops?

Slide 38 · Case resolution: Parvovirus B19

The described erythroid inclusion pattern supports parvovirus B19.

Replication and apoptosis of erythroid precursors produce red cell aplasia.

Severe anemia can contribute to nonimmune fetal hydrops.

The outcome cannot be assumed in all maternal infections; Most have a normal pregnancy outcome.

Distinctive cell tropism explains the hematologic phenotype.

Slide 39 · Congenital CMV: Route and timing

Primary maternal CMV infection

Transplacental viral transmission

Congenital CMV spectrum

Congenital (in utero) CMV from perinatal acquisition at birth or via breast milk.

Congenital disease may be severe, mild, or asymptomatic initially.

Slide 40 · CMV cytopathic morphology: The “owl’s eye” pattern

Enlargement of the infected cell and nucleus

Basophilic intranuclear inclusion with a surrounding clear halo

Additional smaller cytoplasmic inclusions may be present

Schematic—not a diagnostic micrograph. Diagnosis requires appropriate testing and context.

Slide 41 · Congenital CMV: Major injury patterns

Growth

Intrauterine growth restriction may occur.

Visceral

Jaundice and hepatosplenomegaly.

Hematologic

Anemia and thrombocytopenia-associated bleeding.

CNS

Encephalitis; Microcephaly and cerebral calcifications in severe cases.

CMV can involve blood, liver, brain and multiple other tissues.

Slide 42 · Congenital CMV: Delayed neurologic sequelae

Survivors may have permanent hearing loss, intellectual disability, or other neurologic impairment.

Some infants without obvious illness at birth develop deficits later.

A mild neonatal clinical presentation does not completely exclude long-term consequences.

Congenital infection can have a delayed disease phenotype.

Slide 43 · Congenital CMV: Diagnostic clue

Congenital CMV is usually diagnosed by PCR detection of CMV DNA in neonatal urine or saliva.

Cytomegalic inclusions describe a morphologic effect but are not required to appear in every clinical sample.

Differentiate congenital acquisition from infection acquired through birth canal secretions or breast milk.

Interpret test results with sampling time and clinical acquisition context.

Slide 44 · Congenital toxoplasmosis: Chain of transmission

Active maternal Toxoplasma infection

Transplacental organism spread

Fetal eye and brain injury

Vertical transmission in pregnancy and frequent delayed recognition.

The organism is an intracellular protozoan.

Slide 45 · Congenital toxoplasmosis: Source-described findings

Eye

Chorioretinitis; Congenital ocular disease may be bilateral.

Cerebral fluid spaces

Hydrocephalus may occur.

Brain

Microcephaly, cerebral calcifications and neurocognitive deficits.

Pregnancy

Fetal death or abortion in severe cases.

Combine ocular and central nervous system findings rather than assigning an isolated symptom.

Slide 46 · Toxoplasmosis may declare itself after birth

Infants with congenital toxoplasmosis may not become symptomatic until months or years later.

Serologic diagnosis and PCR of blood or cerebrospinal fluid as diagnostic approaches.

Congenital manifestations should be distinguished from later-acquired ocular toxoplasmosis.

Absence of a neonatal symptom does not conclusively exclude congenital infection.

Slide 47 · Congenital syphilis: Maternal-to-fetal spread

Maternal Treponema pallidum infection

Transplacental spirochetal spread

Congenital disease or pregnancy loss

Greater congenital transmission burden during untreated early maternal disease when organisms are numerous.

Infantile and tardive clinical syndromes differ.

Slide 48 · Infantile congenital syphilis

Manifestations in the first two years include nasal congestion and discharge (“snuffles”).

Desquamating or bullous eruptions can involve palms, soles and periorificial skin.

Hepatomegaly and skeletal abnormalities are frequent findings.

Skin, upper airway, visceral and bone disease may coexist.

Slide 49 · Congenital syphilis: Structural pathology

Bone

Osteochondritis and periostitis; Bowing of tibiae may occur.

Liver

Diffuse fibrosis, lymphoplasmacytic inflammation and vascular changes.

Lung

Interstitial fibrosis; Severe stillborn cases may show pneumonia alba.

Multiorgan

Spirochetemia can evoke interstitial inflammation in many tissues.

Slide 50 · Tardive congenital syphilis: Classical triad

Interstitial keratitis

Corneal inflammation is a classical late consequence.

Hutchinson teeth

Characteristic small notched or peg-like incisors.

Eighth-nerve deafness

Hearing deficit associated with later congenital disease.

Late signs represent sequelae of congenital infection, not necessarily new acquisition.

Slide 51 · Listeriosis: Pregnancy-to-neonate spectrum

Maternal Listeria infection

Placental / fetal infection

Abortion, stillbirth or neonatal sepsis

Pregnant patients and neonates are especially susceptible to severe infection.

The pathogen is a gram-positive, facultatively intracellular bacillus.

Slide 52 · Neonatal listeriosis: Morphology and presentation

Dissemination

Granulomatosis infantiseptica may involve many organs.

Inflammation

Acute exudative lesions, abscesses and necrotic nodules.

Placenta

Listerial abscesses may be present.

Clinical

Sepsis, meningitis, and sometimes a red papular extremity rash.

Listeria illustrates why bacterial transplacental infections cannot be overlooked.

Slide 53 · Different pathogens, different dominant clues

Agent

Textbook-highlighted pathology

Clinical association

B19

Inclusions in erythroid precursors

Red cell aplasia, anemia, nonimmune hydrops

CMV

Cytomegalic cells with “owl’s eye” inclusion

FGR, CNS, hematologic, hearing effects

T. gondii

Protozoal tissue cysts / tachyzoites

Chorioretinitis, cerebral lesions

T. pallidum

Interstitial visceral and osseous lesions

Early rash; late keratitis, teeth, deafness

Listeria

Abscesses and exudative inflammation

Maternal loss, neonatal sepsis or meningitis

These are discriminating examples, not exhaustive criteria.

Slide 54 · Why congenital infection and perinatal sepsis overlap

Congenital hematogenous infection

Perinatal sepsis syndrome

The organism reaches fetal blood during gestation.

Clinical illness may emerge around or after delivery.

May cause fetal injury and congenital anomalies.

Pneumonia, sepsis and meningitis can dominate presentation.

Some manifestations arise months or years later.

Age at onset is useful but does not alone define the route.

Time of illness does not uniquely determine the place of acquisition.

Slide 55 · Perinatal sepsis: Terminology

Syndrome

Timing in source

Emphasis

Early onset

First 7 days of life

Often acquired at or shortly before delivery

Late onset

7 days to 3 months

Listeria and Candida may have longer latent intervals

This is clinical sepsis terminology; It is not a classification of congenital malformations.

Slide 56 · Source-based testing and morphology clues

Agent

Example clue documented by Robbins

Parvovirus B19

Distinctive intranuclear inclusions in early erythroid precursors

CMV

Viral DNA PCR using neonatal urine or saliva

Toxoplasma

Serologic testing; PCR of blood or CSF in appropriate settings

Syphilis

Treponemal and nontreponemal serologic algorithms

Listeria

Gram-positive bacilli may be seen in CSF or neonatal meconium smear

These are source-derived diagnostic examples, not a complete neonatal investigation guideline.

Slide 57 · Integrated case: Growth restriction and multisystem disease

A growth-restricted neonate has jaundice, hepatosplenomegaly, anemia and signs of neurologic injury. The maternal history is incomplete; The timing of acquisition is unknown.

1. Which congenital infections enter the differential based on the source?

2. What additional observations would help discriminate the agents?

Slide 58 · Integrated case: Do not force a single diagnosis

Congenital CMV specifically links FGR, jaundice, hepatosplenomegaly, anemia and neurologic disease.

The shared TORCH spectrum means toxoplasmosis, syphilis and other pathogens remain part of the broader consideration.

Look for agent-specific patterns and source-supported tests instead of treating the constellation as pathognomonic.

CMV is a strong source-based pattern match, not a diagnosis without corroboration.

Slide 59 · Integrating pathology across organ systems

Mechanism

Ask how the agent reaches fetal tissues and what cells it targets.

Morphology

Locate the characteristic cellular or tissue lesion where one is described.

Phenotype

Connect the lesion to anemia, organ dysfunction, growth failure or malformation.

Time course

Separate prenatal fetal injury from late expression of consequences.

Slide 60 · High-yield synthesis

Transplacental hematogenous infection reaches fetal blood through chorionic villi; Ascending infection is a separate but potentially overlapping route.

Organism identity and gestational timing govern the fetal clinical-pathologic pattern.

Parvovirus B19 is distinctive for erythroid progenitor injury, red cell aplasia and possible nonimmune hydrops.

TORCH presentations overlap; Morphology, timing and agent-directed evaluation refine the diagnosis.

Hematologic route, specific cell tropism, fetal development and phenotype belong in one explanation.

Slide 61 · Principal references

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. (2026). Chapter 10: Perinatal Infections; Fetal Hydrops; Fetal Growth Restriction.

Robbins, Cotran & Kumar. 11th ed. Chapter 8: Cytomegalovirus; Toxoplasmosis; Syphilis; Listeriosis.

Illustrative pathways and comparisons are original editable teaching schematics based on these source sections.