Congenital rubella syndrome

White pupils due to congenital cataracts in a child with congenital rubella syndrome
Specialty| Teratology

Congenital rubella infection (CRI) occurs when a fetus contracts the rubella virus (German measles) via maternal-fetal transmission. It can result in various outcomes ranging from asymptomatic infection to congenital defects to miscarriage and fetal death.[1] Congenital rubella syndrome (CRS) refers to a congenital rubella infection that results in various presentations of birth anomalies.[2] If infection occurs 0–11 weeks after conception, the infant has a 90% risk of being affected. If the infection occurs 12–20 weeks after conception, the risk is 20%. Infants are not generally affected if rubella is contracted during the third trimester.[1] Congenital rubella syndrome was discovered in 1941 by Australian Norman McAlister Gregg.[3]

The most common congenital defects affect the ophthalmologic, cardiac, auditory, and neurologic systems. [4] Diagnosis of congenital rubella syndrome is made through a series of clinical and laboratory findings and management is based on the infant’s clinical presentation. Maintaining rubella outbreak control via vaccination is essential in preventing congenital rubella infection and congenital rubella syndrome.[1]

## Contents

* 1 Signs and symptoms
* 2 Diagnosis
* 3 Prevention
* 4 Management
* 4.1 Auditory Care
* 4.2 Ophthalmologic Care
* 4.3 Cardiac Care
* 5 References

## Signs and symptoms

Infant with skin lesions from congenital rubella

"Salt-and-pepper" retinopathy is characteristic of congenital rubella.[5][6]

The classic triad for congenital rubella syndrome is:[7]

* Sensorineural deafness (58% of patients)
* Eye abnormalities—especially retinopathy, cataract, glaucoma, and microphthalmia (43% of patients)
* Congenital heart disease—especially pulmonary artery stenosis and patent ductus arteriosus (50% of patients)[8]

Other manifestations of CRS may include:

* Spleen, liver, or bone marrow problems (some of which may disappear shortly after birth)
* Intellectual disability
* Small head size (microcephaly)
* Low birth weight[9]
* Thrombocytopenic purpura, leading to easy or excessive bleeding or bruising
* Extramedullary hematopoiesis (presents as a characteristic blueberry muffin rash)
* Enlarged liver (hepatomegaly)
* Small jaw size (micrognathia)
* Skin lesions [9]

Children who have been exposed to rubella in the womb should also be watched closely as they age for any indication of:

* Developmental delay[9]
* Autism[10]
* Schizophrenia[11]
* Growth retardation[12]
* Learning disabilities
* Diabetes mellitus[13]

## Diagnosis

Congenital rubella serology timeline

Diagnosis of congenital rubella syndrome is made based on clinical findings and laboratory criteria. [1] Laboratory criteria includes at least one of the following:

* Detection of the rubella virus via RT-PCR
* Detection of rubella-specific IgM antibody
* Detection of infant rubella-specific IgG antibody at higher levels (and persists for a longer time) than expected for passive maternal transmission
* Isolation of the rubella virus by nasal, blood, throat, urine, or cerebrospinal fluid specimens

Clinical definition is characterized by findings in the following categories:

1. Cataracts/congenital glaucoma, congenital heart disease (most commonly, patent ductus arteriosus or peripheral pulmonary artery stenosis), hearing impairment, pigmentary retinopathy
2. Purpura, hepatosplenomegaly, jaundice, microcephaly, developmental delay, meningoencephalitis, radiolucent bone disease

A patient is classified into the following cases depending on their clinical and laboratory findings: [1]

* Suspected: A patient that has one or more of the clinical findings listed above but does not meet the definition for probable or confirmed classification
* Probable: A patient that does not have laboratory confirmation of congenital rubella but has either two clinical findings from Group 1 as listed above OR one clinical finding from Group 1 and one clinical finding from Group 2 as listed above
* Confirmed: A patient with at least one laboratory finding and one clinical finding (from either group) as listed above
* Infection only: A patient with no clinical findings as described above but meeting at least one confirmed laboratory criteria

## Prevention

Vaccinating the majority of the population is effective at preventing congenital rubella syndrome.[14] With the introduction of the rubella vaccine in 1969, the number of cases of rubella in the United States has decreased 99%, from 57,686 cases in 1969 to 271 cases in 1999.[1] For women who plan to become pregnant, the MMR (measles mumps, rubella) vaccination is highly recommended, at least 28 days prior to conception.[9] The vaccine should not be given to women who are already pregnant as it contains live viral particles.[9] Other preventative actions can include the screening and vaccinations of high-risk personnel, such as medical and child care professions.[15]

Infants with birth defects suspected to be caused by congenital rubella infection should be investigated thoroughly. Confirmed cases should be reported to the local or state health department to assess control of the virus and isolation of the infant should be maintained.[4]

## Management

Infants with known rubella exposure during pregnancy or those with a confirmed or suspected infection should receive close follow-up and supportive care. There are no medications or antivirals that will shorten the clinical course of the virus.[2] Only those with immunity to rubella should have contact with infected infants, as they can shed viral particles in their respiratory secretions though 1 year of age (unless they test with repeated negative viral cultures at age 3 months).[1] Many infants can be born with multiple birth defects that require multidisciplinary management and interventions based on clinical manifestations. Often times these infants will require extended period or life-long follow up with medical specialists.

### Auditory Care

Many infants with CRS may be born with sensorineural deafness and thus should undergo a newborn hearing evaluation. Hearing loss may not be apparent at birth and thus requires close auditory follow up. Infants with confirmed hearing impairment may require hearing aids and may benefit from an early intervention program.[2]

### Ophthalmologic Care

Eye abnormalities including cataracts, infantile glaucoma and retinopathy are common in infants born with CRS.[4] Infants should undergo eye examinations after birth and during early childhood. Those with congenital eye defects require care from a pediatric ophthalmologist for specialized care and follow up.[2]

### Cardiac Care

Congenital cardiac anomalies including pulmonary artery stenosis and patent ductus arteriosus can be seen in infants with CRS. Infants should undergo cardiac evaluation soon after birth and those with confirmed cardiac lesions will require specialized care with a pediatric cardiologist for any interventions and follow-up care.[2]

## References

1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "Control and prevention of rubella: evaluation and management of suspected outbreaks, rubella in pregnant women, and surveillance for congenital rubella syndrome". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports 50 (RR-12): 1–23. 2001-07-13. ISSN 1057-5987. PMID 11475328. https://pubmed.ncbi.nlm.nih.gov/11475328.
2. ↑ 2.0 2.1 2.2 2.3 2.4 Arrieta, Antonio C.. "Congenital rubella". https://www.uptodate.com/contents/congenital-rubella.
3. ↑ Atkinson, William (2011). Epidemiology and Prevention of Vaccine-Preventable Diseases (12th ed.). Public Health Foundation. pp. 301–323. ISBN 9780983263135. https://www.cdc.gov/vaccines/pubs/pinkbook/rubella.html. Retrieved 30 March 2015.
4. ↑ 4.0 4.1 4.2 "Rubella", Red Book (2021) (American Academy of Pediatrics): pp. 648–655, 2021-05-17, ISBN 978-1-61002-522-5, http://dx.doi.org/10.1542/9781610025225-part03-ch120, retrieved 2023-02-09
5. ↑ "Current approach in the diagnosis and management of posterior uveitis". Indian J Ophthalmol 58 (1): 29–43. 2010. doi:10.4103/0301-4738.58470. ISSN 0301-4738. PMID 20029144.
6. ↑ Khurana, Rahul N.; Sadda, Srinivas R. (3 Aug 2006). "Salt-and-Pepper Retinopathy of Rubella". N Engl J Med 355 (5): 499. doi:10.1056/NEJMicm040780. https://www.nejm.org/doi/full/10.1056/NEJMicm040780.
7. ↑ "Congenital rubella syndrome | Sense". http://www.sense.org.uk/content/congenital-rubella-syndrome.
8. ↑ "An update on cardiovascular malformations in congenital rubella syndrome.". Birth Defects Research Part A: Clinical and Molecular Teratology 88 (1): 1–8. January 2010. doi:10.1002/bdra.20621. PMID 19697432. https://zenodo.org/record/1229131.
9. ↑ 9.0 9.1 9.2 9.3 9.4 "Congenital Rubella Symptoms & Causes | Boston Children's Hospital". http://www.childrenshospital.org/conditions-and-treatments/conditions/c/congenital-rubella/symptoms-and-causes.
10. ↑ Muhle, R; Trentacoste, SV; Rapin, I (May 2004). "The genetics of autism.". Pediatrics 113 (5): e472–86. doi:10.1542/peds.113.5.e472. PMID 15121991. http://pediatrics.aappublications.org/content/113/5/e472.full.
11. ↑ Brown, A. S (9 February 2006). "Prenatal Infection as a Risk Factor for Schizophrenia". Schizophrenia Bulletin 32 (2): 200–202. doi:10.1093/schbul/sbj052. PMID 16469941.
12. ↑ Naeye, Richard L. (1965-12-20). "Pathogenesis of congenital rubella". JAMA 194 (12): 1277–1283. doi:10.1001/jama.1965.03090250011002. ISSN 0098-7484. PMID 5898080.
13. ↑ Forrest, Jill M.; Menser, Margaret A.; Burgess, J. A. (1971-08-14). "High Frequency of Diabetes Mellitus in Young Adults with Congenital Rubella". The Lancet 298 (7720): 332–334. doi:10.1016/S0140-6736(71)90057-2. PMID 4105044.
14. ↑ "Rubella vaccines: WHO position paper.". Wkly Epidemiol Rec 86 (29): 301–16. 15 July 2011. PMID 21766537. https://www.who.int/wer/2011/wer8629.pdf.
15. ↑ "Congenital Rubella - Pediatrics" (in en-US). https://www.merckmanuals.com/professional/pediatrics/infections-in-neonates/congenital-rubella.

Classification|

* ICD-10: P35.0
* ICD-9-CM: 771.0
* MeSH: D012410
* DiseasesDB: 11729

|

External resources|

* MedlinePlus: 001658
* eMedicine: emerg/388

* v
* t
* e

Infectious skin disease: Viral cutaneous conditions, including viral exanthema (B00–B09, 050–059)

| DNA virus|

| Herpesviridae|

| Alpha|

| HSV|

* Herpes simplex
* Herpetic whitlow
* Herpes gladiatorum
* Herpes simplex keratitis
* Herpetic sycosis
* Neonatal herpes simplex
* Herpes genitalis
* Herpes labialis
* Eczema herpeticum
* Herpetiform esophagitis

|

Herpes B virus|

* B virus infection

VZV|

* Chickenpox
* Herpes zoster
* Herpes zoster oticus
* Ophthalmic zoster
* Disseminated herpes zoster
* Zoster-associated pain
* Modified varicella-like syndrome

Beta|

* Human herpesvirus 6/Roseolovirus
* Exanthema subitum
* Roseola vaccinia
* Cytomegalic inclusion disease

Gamma|

* KSHV
* Kaposi's sarcoma

Poxviridae|

| Ortho|

* Variola
* Smallpox
* Alastrim
* MoxV
* Monkeypox
* CPXV
* Cowpox
* VV
* Vaccinia
* Generalized vaccinia
* Eczema vaccinatum
* Progressive vaccinia
* Buffalopox

|

Para|

* Farmyard pox: Milker's nodule
* Bovine papular stomatitis
* Pseudocowpox
* Orf
* Sealpox

Other|

* Yatapoxvirus: Tanapox
* Yaba monkey tumor virus
* MCV
* Molluscum contagiosum

Papillomaviridae|

| HPV|

* Wart/plantar wart
* Heck's disease
* Genital wart
* giant
* Laryngeal papillomatosis
* Butcher's wart
* Bowenoid papulosis
* Epidermodysplasia verruciformis
* Verruca plana
* Pigmented wart
* Verrucae palmares et plantares

|

* BPV
* Equine sarcoid

Parvoviridae|

* Parvovirus B19
* Erythema infectiosum
* Reticulocytopenia
* Papular purpuric gloves and socks syndrome

Polyomaviridae|

* Merkel cell polyomavirus
* Merkel cell carcinoma

RNA virus|

| Paramyxoviridae|

* MeV
* Measles

|

Togaviridae|

* Rubella virus
* Rubella
* Congenital rubella syndrome ("German measles" )
* Alphavirus infection
* Chikungunya fever

Picornaviridae|

* CAV
* Hand, foot, and mouth disease
* Herpangina
* FMDV
* Foot-and-mouth disease
* Boston exanthem disease

Ungrouped|

* Asymmetric periflexural exanthem of childhood
* Post-vaccination follicular eruption
* Lipschütz ulcer
* Eruptive pseudoangiomatosis
* Viral-associated trichodysplasia
* Gianotti–Crosti syndrome

* v
* t
* e

Certain conditions originating in the perinatal period / fetal disease (P, 760–779)

Maternal factors and
complications of pregnancy,
labour and delivery|

| placenta:|

* Placenta praevia
* Placental insufficiency
* Twin-to-twin transfusion syndrome

|

chorion/amnion:|

* Chorioamnionitis

umbilical cord:|

* Umbilical cord prolapse
* Nuchal cord
* Single umbilical artery

presentation:|

* Breech birth
* Asynclitism
* Shoulder presentation

Length of gestation
and fetal growth|

* Small for gestational age/Large for gestational age
* Preterm birth/Postmature birth
* Intrauterine growth restriction

Birth trauma|

* scalp
* Cephalhematoma
* Chignon
* Caput succedaneum
* Subgaleal hemorrhage
* Brachial plexus lesion
* Erb's palsy
* Klumpke paralysis

By system|

| Respiratory|

* Intrauterine hypoxia
* Infant respiratory distress syndrome
* Transient tachypnea of the newborn
* Meconium aspiration syndrome
* pleural disease
* Pneumothorax
* Pneumomediastinum
* Wilson–Mikity syndrome
* Bronchopulmonary dysplasia

|

Cardiovascular|

* Pneumopericardium
* Persistent fetal circulation

Haemorrhagic and
hematologic disease|

* Vitamin K deficiency bleeding

* HDN
* ABO
* Anti-Kell
* Rh c
* Rh D
* Rh E
* Hydrops fetalis
* Hyperbilirubinemia
* Kernicterus
* Neonatal jaundice

* Velamentous cord insertion
* Intraventricular hemorrhage
* Germinal matrix hemorrhage
* Anemia of prematurity

Digestive|

* Ileus
* Necrotizing enterocolitis
* Meconium peritonitis

Integument and
thermoregulation|

* Erythema toxicum
* Sclerema neonatorum

Nervous system|

* Perinatal asphyxia
* Periventricular leukomalacia

Musculoskeletal|

* Gray baby syndrome
* muscle tone
* Congenital hypertonia
* Congenital hypotonia

Infectious|

* Vertically transmitted infection
* Neonatal infection
* Congenital rubella syndrome
* Neonatal herpes simplex
* Mycoplasma hominis infection
* Ureaplasma urealyticum infection
* Omphalitis
* Neonatal sepsis
* Group B streptococcal infection
* Neonatal conjunctivitis

Other|

* Miscarriage
* Perinatal mortality
* Stillbirth
* Infant mortality
* Neonatal withdrawal

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