Congenital Herpes Simplex Virus Infection

1. Disease Information

Overview

Congenital Herpes Simplex Virus (HSV) infection is a group of congenital anomalies resulting from maternal HSV infection and subsequent fetal/neonatal infection with herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2). It represents a spectrum of disease acquired either in utero (transplacental or ascending infection) or perinatally (during passage through an infected birth canal). The intrauterine form is the rarest and most severe, characterized by a classic triad of cutaneous, neurologic, and ophthalmologic findings (PMID:40027069).

Neonatal HSV disease is traditionally classified into three categories based on the extent of involvement: - Skin, Eye, and Mouth (SEM) disease (~45% of cases) - Central Nervous System (CNS) disease (~30% of cases) - Disseminated disease (~25% of cases)

True congenital (intrauterine) HSV infection accounts for approximately 5% of all neonatal HSV cases, while 85% are acquired peripartum and 10% postnatally (PMID:40027069).

Key Identifiers

Synonyms

• Congenital herpes simplex virus infection
• Intrauterine herpes simplex infection
• Neonatal herpes simplex (broader, includes peripartum acquisition)
• Congenital HSV infection

2. Etiology

Primary Cause

Congenital HSV infection is caused by vertical transmission of Herpes Simplex Virus (HSV-1 or HSV-2, family Herpesviridae, subfamily Alphaherpesvirinae) from an infected mother to the fetus or neonate. HSV is a large, enveloped double-stranded DNA virus (~152 kb genome) encoding approximately 80 proteins.

Routes of vertical transmission: 1. Transplacental (hematogenous): During maternal primary viremia, the virus crosses the placenta — the predominant route for true congenital (intrauterine) infection (PMID:40027069) 2. Ascending infection: Virus ascends from the genital tract through ruptured or intact amniotic membranes 3. Intrapartum contact: Direct contact with infectious secretions in the birth canal (most common overall)

Risk Factors

Maternal factors: - Primary maternal genital HSV infection near delivery: The strongest risk factor. Infants born to women with primary genital HSV infection near delivery have a 25–60% risk of neonatal herpes, compared to <2% with recurrent genital HSV (PMID:2020171; Brown et al., NEJM 1991) - Absence of maternal HSV-specific IgG antibodies: Lack of transplacental protective antibodies leaves the neonate without passive immunity - Prolonged rupture of membranes (>4–6 hours): Increases ascending infection risk - Vaginal delivery with active genital lesions - Use of fetal scalp electrodes: Disrupts neonatal skin barrier

Neonatal/fetal factors: - Prematurity: Immature immune system and skin barrier compromise - Fetal skin barrier disruption: Permits viral entry - Immature neonatal innate immunity: Particularly dampened TLR3–interferon signaling in the newborn brain (PMID:33055261)

Host genetic susceptibility (inborn errors of immunity): Mutations in TLR3 pathway genes predispose to severe HSV disease, particularly HSV encephalitis: - TLR3, UNC93B1, TRIF (TICAM1), TRAF3, TBK1, IRF3, STAT1, IFNAR1, NEMO (IKBKG) - These genetic alterations impair IFN-α/β production within the central nervous system (PMC9961685)

Protective Factors

• Pre-existing maternal HSV-specific antibodies (from prior HSV-1 or HSV-2 infection): Reduce neonatal transmission risk to <2% in recurrent infections
• Cesarean delivery: Reduces neonatal HSV risk by approximately 86% when active genital lesions are present (Brown et al., JAMA 2003)
• Maternal antiviral suppressive therapy from 36 weeks gestation: Reduces viral shedding at delivery and need for cesarean section (PMID:18254066)

3. Phenotypes

Cutaneous Manifestations

Neurological Manifestations

Ophthalmologic Manifestations

Systemic Manifestations

4. Genetic/Molecular Information

Infectious Agent (Not a Mendelian Genetic Disease)

Congenital HSV infection is an infectious disease, not a monogenic disorder. The causative agents are: - HSV-1 (Human alphaherpesvirus 1; NCBITaxon:10298) - HSV-2 (Human alphaherpesvirus 2; NCBITaxon:10310)

Globally, neonatal HSV disease shows near-equal contributions from both serotypes: HSV-1 accounts for 47.3% and HSV-2 for 52.8%, with a temporal shift toward increasing HSV-1 proportion (yearly 1.4% increase in HSV-1 cases) (PMID:41860333).

Host Genetic Susceptibility Loci

While not causative in the Mendelian sense, inborn errors of immunity in the TLR3–IFN signaling pathway markedly increase susceptibility to severe HSV disease:

These defects impair the TLR3-dependent type I interferon response that is particularly critical in the CNS for controlling HSV replication (PMC9961685; PMC10231989). A case report documented neonatal HSV-2 encephalitis associated with a compound heterozygous TLR3 mutation (PMC13485870).

HSV Virology

Viral entry receptors: - Nectin-1 (PVRL1/NECTIN1; hgnc:9706): Primary receptor on neurons and epithelial cells - HVEM (TNFRSF14; hgnc:11912): Herpesvirus entry mediator; expressed on immune cells - 3-O-sulfated heparan sulfate: Modified proteoglycan receptor

Essential entry glycoproteins: gB, gD, gH, gL mediate viral envelope–cell membrane fusion.

5. Environmental Information

Infectious Agents

• Primary agent: HSV-1 (NCBITaxon:10298) and HSV-2 (NCBITaxon:10310)
• HSV-2 has historically been more commonly associated with genital herpes and neonatal transmission, but HSV-1 is increasingly implicated, now representing nearly half of neonatal cases globally (PMID:41860333)

Transmission Route

• ECTO term: Exposure to herpes simplex virus (sexual/mucosal contact)
• Vertical transmission: transplacental, ascending, or intrapartum
• Rare postnatal transmission: via contact with oral/labial HSV lesions (caregivers)

Environmental Risk Modifiers

• Socioeconomic factors influence HSV seroprevalence patterns
• Declining childhood HSV-1 seroprevalence in high-income countries paradoxically increases susceptibility to primary genital HSV-1 infection in young adults, shifting the epidemiology of neonatal herpes

6. Mechanism / Pathophysiology

Causal Chain

1. Maternal HSV infection (primary or reactivation) → maternal genital tract viral shedding or viremia
2. Viral entry into fetal/neonatal tissues → transplacental hematogenous spread (intrauterine) or direct mucosal/skin contact (peripartum) → HSV binds nectin-1/HVEM on epithelial cells and neurons via gD glycoprotein
3. Local viral replication in epithelial cells → cytopathic effect (cell lysis, multinucleated giant cells, Cowdry type A intranuclear inclusions) → leads to skin vesicles and mucosal ulceration (SEM disease)
4. Viral neurotropism and axonal transport → HSV travels retrogradely along sensory nerves to CNS → leads to necrotizing encephalitis with hemorrhagic infarction, particularly in temporal lobes and limbic system (GO:0019079, viral genome replication)
5. Dampened neonatal innate immune response → immature TLR3–IFN-β signaling in newborn brain (PMID:33055261) → failure to contain viral replication in CNS → widespread neuronal destruction, astrocyte activation, microglial inflammation (GO:0045087, innate immune response)
6. HSV immune evasion → ICP34.5 and Us11 inhibit PKR activation; ICP0 degrades PML bodies; gL abrogates NF-κB nuclear translocation (PMC10203706) → leads to unchecked viral replication
7. Placental inflammation (intrauterine infection) → pro-inflammatory mediators detected in fetal tissues; necrotizing villitis, chorioamnionitis, maternal floor infarction (PMID:34696359; PMC9557870) → leads to intrauterine growth restriction, preterm birth, fetal death
8. Hematogenous dissemination → viremia spreads to liver, adrenals, lungs, brain → leads to hepatic necrosis, adrenal hemorrhage, pneumonitis, DIC (disseminated disease)
9. Neuroinflammation and tissue destruction → necrotizing meningoencephalitis → leads to long-term sequelae: microcephaly, hydranencephaly, intracranial calcifications, intellectual disability, seizure disorder

Key Molecular Pathways

• TLR3–TRIF–TBK1–IRF3 pathway (GO:0034154, Toll-like receptor 3 signaling pathway): Critical for IFN-β production in CNS; neonatal immaturity of this pathway underlies susceptibility
• Type I interferon signaling (GO:0060337, type I interferon signaling pathway): IFN-α/β production is dampened in the newborn brain; exogenous IFN-β can rescue survival in mouse models (PMID:33055261)
• NF-κB signaling (GO:0007249): Activated by TLR recognition of viral PAMPs but counteracted by HSV immune evasion
• PKR–eIF2α antiviral pathway: Inhibited by HSV ICP34.5 and Us11
• Apoptosis (GO:0006915): HSV modulates both pro- and anti-apoptotic pathways for viral benefit

Cell Types Involved

Placental Pathology

Histopathological findings in the placenta include (PMC9557870; PMC7817230): - Necrotizing villitis with stromal cell necrosis - Chronic chorioamnionitis - Maternal floor infarction - Calcifying funisitis (umbilical cord) - Positive HSV immunohistochemistry in placenta and umbilical cord - Ascending infection pattern shows changes primarily in the umbilical cord and chorionic plate

7. Anatomical Structures Affected

Organ Level

CNS Localization

• Temporal lobes: Predilection site for HSV encephalitis
• Basal ganglia, thalamus, internal capsules: Poor prognostic indicator when bilateral deep cerebral lesions are present (PMC10406570)
• Brainstem and cerebellum: Can show non-hemorrhagic infarcts
• Leptomeninges: Enhancement on MRI; meningoencephalitis pattern

8. Temporal Development

Onset

• Intrauterine (congenital) disease: Present at birth; affected by timing of maternal infection during pregnancy
• SEM disease: Mean presentation at 7–12 days of life
• CNS disease: Mean presentation at 11–17 days of life
• Disseminated disease: Mean presentation at ~11 days of life (range: birth to 6 weeks)

Onset classification: Neonatal (HP:0003623, Neonatal onset).

Progression

• SEM disease: Self-limited with treatment; risk of recurrence without suppressive therapy
• CNS disease: Acute encephalitis → potential for progressive neurological deterioration → chronic seizure disorder, developmental delay
• Disseminated disease: Rapidly progressive multi-organ failure without treatment
• Intrauterine infection: Damage occurs during fetal development; consequences are often irreversible at birth

Critical Periods

• First trimester maternal infection: Highest risk for severe congenital malformations (organogenesis disruption)
• Late third trimester / peripartum: Highest risk for neonatal transmission due to primary genital infection near delivery
• First 48 hours of life: Window for empiric acyclovir initiation before confirmatory testing

9. Inheritance and Population

Epidemiology

Global incidence (PMID:41860333; systematic review and meta-analysis, 143 reports): - Global pooled incidence: 8.8 per 100,000 live births (95% CI: 6.9–10.9) - Population-weighted global estimate: 8.2 per 100,000 live births (95% CI: 5.9–10.7) - Approximately 1 in 10,000 newborns affected globally - Annual increase of 3.5% (95% CI: 1.5–5.6%) in nHSV incidence

Regional variation: - Americas: 13.3 per 100,000 live births (95% CI: 9.9–17.2) — highest - European Region: 5.2 per 100,000 live births (95% CI: 3.4–7.3) - Western Pacific: 2.9 per 100,000 live births (95% CI: 2.2–3.6) - Data lacking from Africa, South-East Asia, Eastern Mediterranean

True intrauterine HSV infection: Estimated at only 1 in 300,000 deliveries (PMID:40027069).

HSV-1 vs HSV-2 Distribution

• Global: HSV-1 = 47.3%; HSV-2 = 52.8%
• Temporal trend: yearly 1.4% increase in HSV-1 proportion, 1.1% decrease in HSV-2
• Americas: HSV-2 predominates (60.5%)
• Western Pacific: HSV-1 predominates (57.7%)

Population Demographics

• No strong sex predilection in neonatal disease
• Higher incidence in populations with lower HSV seroprevalence in young women (paradoxically, higher socioeconomic populations where primary infection occurs later in life)
• African American women in the US have higher HSV-2 seroprevalence but paradoxically lower neonatal herpes rates (due to pre-existing antibodies conferring partial protection)

10. Diagnostics

Laboratory Testing

• HSV PCR (NAAT): Gold standard for diagnosis; performed on:
• CSF (sensitivity >95% for CNS disease)
• Blood/plasma (viremia in disseminated disease)
• Vesicle fluid/swabs from skin lesions, conjunctivae, oropharynx
• Viral culture: From vesicle fluid or mucosal swabs; less sensitive than PCR but allows serotyping
• Direct fluorescent antibody (DFA) staining: Rapid but less sensitive
• HSV serology: Type-specific IgG (limited utility in neonates due to maternal antibody transfer; useful for maternal screening)

LOINC codes: - HSV DNA detection by NAA: LOINC:16952-4 - HSV culture: LOINC:5857-0

CSF Analysis

• Mononuclear pleocytosis (may be normal early)
• Depressed glucose
• Mildly to moderately elevated protein
• HSV PCR positive (PMID:23481105)

Imaging

• Cranial MRI: Preferred modality
• Diffusion restriction in temporal/frontal lobes
• Hemorrhagic or non-hemorrhagic infarcts
• Leptomeningeal enhancement
• Bilateral deep cerebral lesions (basal ganglia, thalamus) = poor prognosis (PMC10406570)
• Cranial ultrasound: May show echogenic foci, ventriculomegaly
• CT: Intracranial calcifications (especially in intrauterine infection)

Ophthalmologic Examination

• Fundoscopy for chorioretinitis
• Slit-lamp examination for keratitis

Placental Pathology

• Histopathology: necrotizing villitis, chorioamnionitis
• HSV immunohistochemistry of placenta and umbilical cord
• Examination within first 2–5 days of life in premature infants can provide early diagnostic clues (PMC7817230)

EEG

• Abnormal electrical activity, often multifocal seizure discharges
• Periodic lateralized epileptiform discharges (PLEDs) suggestive of HSV encephalitis

Differential Diagnosis

• Other TORCH infections (CMV, toxoplasmosis, rubella, syphilis, Zika)
• Neonatal bacterial sepsis/meningitis
• Enteroviral infection
• Epidermolysis bullosa (for vesicular skin lesions)
• Metabolic disorders presenting with hepatic failure
• Inborn errors of metabolism

11. Outcome / Prognosis

Mortality

(Mortality data from Kimberlin et al., Pediatrics 2001, PMID:11483825; and AAP NeoReviews 2018)

Neurodevelopmental Outcomes

• SEM disease: Generally normal neurodevelopment; risk of recurrent skin lesions
• CNS disease: 30–70% of survivors develop neurodevelopmental impairment including intellectual disability, cerebral palsy, epilepsy, and motor deficits (PMC10406570)
• Disseminated disease: ≥65% of survivors of untreated disease have severe neurologic sequelae; treatment reduces but does not eliminate this
• Intrauterine infection: Associated with the most severe outcomes including spontaneous abortion, stillbirth, severe brain malformations (PMID:40027069)

Prognostic Factors

• Disease classification (SEM > CNS > Disseminated in terms of favorable outcome)
• Timing of acyclovir initiation: Earlier treatment improves outcomes
• CSF HSV PCR negativity at end of treatment: Favorable indicator
• Bilateral deep cerebral MRI lesions: Poor prognostic indicator
• Suppressive oral acyclovir therapy: 6 months post-acute treatment improves neurodevelopmental outcomes (Bayley scores) (Kimberlin et al., NEJM 2011, PMID:21793742)

12. Treatment

Acute Antiviral Therapy

Intravenous acyclovir (NCIT:C275; Acyclovir) — standard of care: - Dose: 20 mg/kg/dose IV every 8 hours - Duration: - SEM disease: 14 days - CNS disease: 21 days (minimum) - Disseminated disease: 21 days (minimum) - CSF monitoring: Repeat lumbar puncture near end of therapy for CNS disease; continue IV acyclovir if CSF PCR remains positive, with weekly repeat LP until negative

NCIT terms: - Pharmacotherapy: NCIT:C15986 - Acyclovir: NCIT:C275

Suppressive Therapy

• Oral acyclovir: 300 mg/m²/dose three times daily for 6 months after completion of IV therapy
• Recommended for all infants surviving neonatal HSV regardless of disease classification
• Improves neurodevelopmental outcomes in CNS disease (PMID:21793742)
• Monitoring: Absolute neutrophil counts (ANCs) should be checked at 2 and 4 weeks after initiation, then monthly; neutropenia is the primary adverse effect

Suggested CHEBI term: CHEBI:2453 (aciclovir)

Supportive Care (NCIT:C15747)

• Seizure management (phenobarbital, levetiracetam)
• Respiratory support as needed
• Nutritional support
• Ophthalmologic follow-up
• Neurodevelopmental monitoring and early intervention services

Emerging Therapies

• Valacyclovir (CHEBI:60726) for neonatal HSV disease is under investigation (NCT04448392) — oral prodrug with improved bioavailability
• Pritelivir (helicase-primase inhibitor) — investigational, novel mechanism distinct from nucleoside analogues

13. Prevention

Primary Prevention

Maternal antiviral suppressive therapy: - Acyclovir 400 mg PO TID or valacyclovir 500 mg PO BID from 36 weeks gestation in women with known recurrent genital HSV - Significantly reduces viral shedding at delivery and cesarean section rates (PMID:18254066) - Insufficient evidence that suppressive therapy alone reduces neonatal herpes incidence (event too rare in trials)

Cesarean delivery: - Recommended when active genital HSV lesions or prodromal symptoms are present at labor onset - Reduces neonatal HSV transmission by ~86%

Screening: - Routine serologic screening for HSV during pregnancy is not recommended by ACOG/SOGC - Type-specific IgG testing can identify discordant couples and guide counseling - No population-based prenatal HSV screening program exists

Secondary Prevention

• Early empiric acyclovir: Initiation upon clinical suspicion, before confirmatory testing, significantly reduces mortality and morbidity
• HSV surface cultures at delivery: Swabs from eyes, nasopharynx, mouth, rectum at 12–24 hours of life in infants born to mothers with active lesions

Tertiary Prevention

• 6-month oral acyclovir suppressive therapy: Prevents cutaneous recurrences and improves neurodevelopmental outcomes
• Long-term neurodevelopmental follow-up
• Ophthalmologic surveillance for delayed visual complications

Counseling

• Education of parents/caregivers about avoiding neonatal contact with active HSV lesions (oral or genital)
• Genetic counseling may be warranted if inborn errors of TLR3–IFN immunity are identified

14. Other Species / Natural Disease

Animal Models

Mouse models: - C57BL/6 mice infected intravaginally with HSV-2 during early pregnancy demonstrate dose-dependent adverse pregnancy outcomes including reduced fetal/placental weights, fetal resorption, and transplacental viral transmission (PMID:34696359) - At low viral doses, infection localizes to fetal eye and CNS; at high doses, disseminated expression in neuroepithelium, heart, and liver - Pregnant mice show ~100-fold greater susceptibility to HSV-2 compared to non-pregnant controls - Newborn mice demonstrate dampened innate immune signaling and IFN responses compared to adults (PMID:33055261) - Hematogenous vertical transmission of HSV-1 in mice with CNS tropism in offspring (PMID:16501086)

Guinea pig models: - Mimic natural history of genital HSV infection with spontaneous recurrences - Used for studying antiviral suppressive therapy and maternal-to-neonatal transmission

Non-human primate models: - Rhesus macaque model for genital HSV-2 with vaginal vesicular lesions, virus shedding, and seroconversion (PMC11371218) - Most relevant to human disease due to immunological similarity

Natural Disease in Other Species

HSV-1 and HSV-2 are highly host-restricted to humans. Natural HSV infection in non-human animals is rare and typically represents cross-species transmission. B virus (Macacine alphaherpesvirus 1), an HSV homolog in Old World macaques, causes a similar but zoonotic disease.

15. Model Organisms (Research Models)

Summary of Key Ontology Term Suggestions

Sources

• Intrauterine Herpes Simplex Virus Infection: Insights Into a Silent Threat (2025, PMID:40027069)
• Global epidemiology of neonatal herpes: systematic review, meta-analyses, and meta-regressions (2026, PMID:41860333)
• Congenital Herpes Simplex — StatPearls
• Congenital Herpes Simplex Virus: A Histopathological View of the Placenta (2022)
• Diagnosis of Neonatal Herpes Simplex Infection from the Placenta (2021)
• The Many Faces of Neurological Neonatal HSV Infection (2023)
• Neonatal Herpes Simplex Virus Infection — AAP NeoReviews (2018)
• Neonatal herpes simplex virus infection: From the maternal infection to the child outcome (De Rose et al., 2023)
• Primary HSV-2 Infection in Early Pregnancy — Novel Mouse Model (2021, PMID:34696359)
• The Innate Immune Response to HSV-1 in the Newborn Brain (2020, PMID:33055261)
• Inborn Errors of Immunity Predisposing to HSV Infections of the CNS (2023)
• The immunogenetic basis of severe HSV in neonates and children (2025)
• A case of neonatal HSV-2 encephalitis with TLR3 gene mutation (2025)
• Third trimester antiviral prophylaxis for preventing neonatal HSV (Cochrane, PMID:18254066)
• Oral Acyclovir Suppression and Neurodevelopment after Neonatal Herpes (Kimberlin et al., NEJM 2011, PMID:21793742)
• Safety and Efficacy of High-Dose IV Acyclovir in Neonatal HSV (Kimberlin et al., Pediatrics 2001)
• Neonatal HSV in Relation to Asymptomatic Maternal Infection (Brown et al., NEJM 1991, PMID:2020171)
• Effect of Serologic Status and Cesarean Delivery on HSV Transmission (Brown et al., JAMA 2003)
• Congenital herpes simplex with ophthalmic and multisystem features (2023)
• ICD-10-CM Code P35.2
• Orphanet: Congenital herpes simplex virus infection (ORPHA:293)
• Hematogenous Vertical Transmission of HSV-1 in Mice (2006, PMID:16501086)
• Animal models of human herpesvirus infection (2025)
• Congenital Herpes Simplex Virus Infection — MalaCards

Reference Validation

Checked with linkml-reference-validator 0.3.0rc3.

References that may not be about this subject

These identifiers resolve, so they are not fabrications, but the records they resolve to share almost none of this report's vocabulary. That is a clue and not a verdict - a paper can be relevant in ways its title and abstract do not spell out - so read them before deciding:

• PMID:2020171 (2 mentions) - Subcritical flutter in collapsible tube flow: a model of expiratory flow in the trachea.
• shared terms: none

Weighed against this report's own most characteristic terms: hsv, infection, disease, neonatal, cns, intrauterine, herpe, disseminated, lesion, primary, hsv-2, congenital, genital, maternal, transmission, hsv-1, viral, acyclovir, virus, skin.

All extracted references resolved successfully. Resolving is not the same as being relevant, though - see the references listed above as possibly off topic.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

• MONDO:0017381 (2 mentions) - the report calls it "MONDO", "Congenital herpes simplex virus infection"; MONDO calls it congenital herpes simplex virus infection
• HP:0002340 (2 mentions) - the report calls it "Hydranencephaly"; HP calls it Caudate atrophy
• HP:0000483 (2 mentions) - the report calls it "Chorioretinitis"; HP calls it Astigmatism
• HP:0005765 (1 mention) - the report calls it "DIC"; HP calls it Sacral meningocele
• CHEBI:60726 (1 mention) - the report calls it "Valacyclovir"; CHEBI calls it procainamide 4-hydroxylamine

Unresolved terms

These identifiers do not exist in an ontology that resolved other terms from the same prefix, so they were most likely invented:

• HP:0045023 (1 mention) - HP does not contain this term

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

• HP:0001250 (3 mentions) - the report calls it "Seizures", "Epilepsy"; HP calls it Seizure, and lists "Epilepsy" among its other names
• HP:0002514 (2 mentions) - the report calls it "Intracranial calcifications"; HP calls it Cerebral calcification
• HP:0000563 (1 mention) - the report calls it "Keratoconjunctivitis"; HP calls it Keratoconus
• HP:0012115 (1 mention) - the report calls it "Hepatic failure"; HP calls it Hepatitis
• HP:0006517 (1 mention) - the report calls it "Alveolar hemorrhage"; HP calls it Intraalveolar phospholipid accumulation, and lists "Alveolar proteinosis" among its other names
• HP:0001511 (2 mentions) - the report calls it "Intrauterine growth restriction"; HP calls it Intrauterine growth retardation, and lists "Intrauterine growth restriction" among its other names
• NCBITaxon:10298 (3 mentions) - the report calls it "Primary agent: HSV-1"; NCBITaxon calls it Human alphaherpesvirus 1**, and lists "HSV-1" among its other names
• GO:0007249 (1 mention) - the report calls it "NF-κB signaling"; GO calls it canonical NF-kappaB signal transduction, and lists "p50-dependent NF-kappaB signaling" among its other names
• GO:0006915 (2 mentions) - the report calls it "Apoptosis"; GO calls it apoptotic process, and lists "apoptosis" among its other names
• CL:0000351 (2 mentions) - the report calls it "Trophoblast"; CL calls it trophoblast cell
• UBERON:0002097 (2 mentions) - the report calls it "Skin"; UBERON calls it skin of body, and lists "skin" among its other names
• CHEBI:2453 (2 mentions) - the report calls it "aciclovir"; CHEBI calls it acyclovir, and lists "aciclovir" among its other names

Terms named inconsistently

The report gives these identifiers more than one name of its own:

• MONDO:0017381 - called "MONDO", "Congenital herpes simplex virus infection"
• HP:0001250 - called "Seizures", "Epilepsy"

Prefixes with no resolver

Terms carrying these prefixes were not checked either way, because no configured ontology covers them. An unrecognised prefix may name an ontology this run could not reach as easily as one that does not exist, so nothing here is evidence of fabrication: ORPHA, LOINC.