Congenital rubella syndrome overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]
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Overview
In 1941, congenital rubella syndrome was recognized as a complication of rubella infection among pregnant women who became infected with the virus early in their pregnancy. An Australian ophthalmologist made the connection and reported 78 cases of congenital cataract among infants born to mothers who had a rubella infection early in their pregnancy. The pathogenesis of congenital rubella syndrome is multifactorial. However, pregnant women who are not vaccinated against rubella are at high risk of contracting the infection. If they get infected during pregnancy, the virus can infect the placenta and spread to the fetus, leading to disruption of the normal process of organogenesis. Rubella virus has largely been eradicated in many parts of the developed world. However, in the developing world where MMR vaccine is not available or accessible, infection with rubella and consequently, congenital rubella syndrome is an important health issue. Many of the congenital infections have overlapping features and hence, congenital rubella must be differentiated from the other TORCH infections. Congenital rubella syndrome affects multiple organ systems. The classic triad consists of cataracts, sensorineural hearing loss and patent ductus arteriosus (PDA).
Historical Perspective
Originally, rubella was referred to as the third disease, because it was thought to branch from measles or Scarlet fever. However, in 1814, it was recognized as a separate entity of disease and became known as German measles.[1][2] In 1941, congenital rubella syndrome was recognized as a complication of rubella infection among pregnant women who became infected with the virus early in their pregnancy.[1][2] An Australian ophthalmologist made the connection and reported 78 cases of congenital cataract among infants born to mothers who had a rubella infection early in their pregnancy.[1][2]
Classification
There is no classification scheme for congenital rubella syndrome. However, in 2009, the CDC published the case classification of congenital rubella syndrome and divided into suspected cases, probable cases, confirmed cases and infection only, based on symptoms and/or laboratory findings.[3]
Pathophysiology
The pathogenesis of congenital rubella syndrome is multifactorial. However, pregnant women who are not vaccinated against rubella are at high risk of contracting the infection. If they get infected during pregnancy, the virus can infect the placenta and spread to the fetus, leading to disruption of the normal process of organogenesis. The degree of severity of malformations depends on the gestational age of the onset of infection. The highest risk of fetal anomalies or poor pregnancy outcomes such as spontaneous abortion and stillbirth is highest if a woman becomes infected prior to conception or in the in the first 8-10 weeks of gestation.[1][4][5][6][7]
Causes
The cause of congenital rubella syndrome is rubella virus. Rubella virus is a single-stranded, positive-sense RNA virus (ssRNA). It is the only member of the genus Rubivirus and belongs to the family of Togaviridae.
Differentiating Congenital Rubella Syndrome from other Diseases
The most important congenital infections, which can be transmitted vertically from mother to fetus are the TORCH infections. These infections have overlapping features and hence, must be differentiated from CRS.[8][9]
Epidemiology and Demographics
The exact incidence of congenital rubella syndrome is hard to estimate, because in many parts of the developing world rubella has been eliminated. However, very few cases are still reported in the U.S and they are believed to be imported cases. In addition, rubella infection and congenital rubella syndrome are still a challenge in the developing world, with most cases occurring in Africa and Southeast Asia.[5][10]In countries without rubella immunization, the incidence is estimated to range between 60-220 per 100,000 cases.[11]
Risk Factors
Screening
There is no screening test for congenital rubella syndrome.[12]
Natural History, Complications and Prognosis
Congenital rubella syndrome can cause serious birth defects and the prognosis depends on the severity of the problem. Heart defects can be corrected but neurological damage is permanent.[1][4][13][8][9][5]
History and Symptoms
The symptoms of rubella in the pregnant woman are similar to those seen in any child or adult with rubella infection. Of note, young women are more likely to suffer from sequelae of polyarthritis and polyarthralgia. In the infant, symptoms such as irritability, low birth weight, skin lesions, white appearance to the cornea may be seen and be suggestive of congenital rubella syndrome.[14][15][16][2][17][1][4][9][18][19]
Physical Examination
Congenital rubella syndrome affects multiple organ systems. The classic triad of congenital rubella syndrome consists of cataracts, sensorineural hearing loss and patent ductus arteriosus (PDA). However, many other findings are evident on physical examination, including low birth weight, skin lesions and hepatosplenomegaly.[1][4][9][18][19]
Laboratory Findings
Prenatal testing consists of direct isolation of the virus, viral nucleic acid quantification or detection of antibodies against rubella in fetal blood via various invasive techniques, such as amniocentesis, fetal blood sampling and chorionic villi sampling.[1][20][21][22][23] Postnatal testing consists of isolation of the virus from throat or urine cultures[3] and detection of serology (IgG or IgM antibodies against rubella).[1][24][25][26][27][28] Other laboratory findings in infants with congenital rubella syndrome include thrombocytopenia and elevated levels of PT, PTT and bilirubin.[9]
Electrocardiogram
Electrocardiogram findings in a child of congenital rubella syndrome depends on the type of heart defect (mostly PDA) and its severity.
Chest X Ray
The chest radiograph may show increased pulmonary vascularity and cardiomegaly due to ventricular enlargement. The heart size might be normal if the shunt is small. However, CXR findings depend on the size and type of associated heart defect.
CT Scan
Congenital rubella syndrome is associated with craniofacial abnormalities, most commonly microcephaly or hydrocephaly. Hence, CT scan is able to assess the underlying brain and the forebrain is usually most affected.[29] In addition, a multi-detector CT scan (MDCT) is used to detect the various cardiac anomalies associated with congenital rubella syndrome. Findings such as patent ductus arteriosus, its degree of severity as well as other associated cardiac anomalies may be seen.[30]
MRI
Congenital rubella syndrome is associated with craniofacial abnormalities, most commonly microcephaly or hydrocephaly. Hence, MRI is able to assess the underlying brain and the forebrain is usually most affected.[29]
Echocardiography and Ultrasound
On echocardiography, the several cardiac anomalies associated with congenital rubella syndrome may be seen. These include patent ductus arteriosus, pulmonary artery stenosis, coarctation of the aorta, as well as septal defects (VSD or ASD).[18][31] Prenatal ultrasound, although not sensitive, is highly specific in detecting the various anomalies associated with congenital rubella syndrome. Findings such as IUGR, fetal hydrops, microcephaly, cardiac and ophthalmic defects may be seen on ultrasound.[1][5][32]
Other Imaging Findings
There are no other imaging findings associated with congenital rubella syndrome.
Other Diagnostic Studies
There are no other diagnostic studies associated with congenital rubella syndrome.
Medical Therapy
There is no specific medical treatment for congenital rubella syndrome.[33]
Surgery
The role of surgery in patients with congenital rubella syndrome consists of treating the several cardiac[34], ophthalmic[35][36] and hearing complications that arise as a result.[1][4][9][18][19]
Primary Prevention
MMR vaccination prior to pregnancy can prevent congenital rubella syndrome.[4]
Secondary Prevention
Infants with congenital rubella syndrome should be placed in isolation during their hospital stay. In addition, appropriate measures should be taken to ensure that all healthcare workers and caregivers of the infected child are immune to rubella.[3]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 De Santis M, Cavaliere AF, Straface G, Caruso A (2006). "Rubella infection in pregnancy". Reprod. Toxicol. 21 (4): 390–8. doi:10.1016/j.reprotox.2005.01.014. PMID 16580940.
- ↑ 2.0 2.1 2.2 2.3 Cooper LZ, Krugman S (1967). "Clinical manifestations of postnatal and congenital rubella". Arch. Ophthalmol. 77 (4): 434–9. PMID 4164540.
- ↑ 3.0 3.1 3.2 Center for Disease Control and Prevention https://www.cdc.gov/vaccines/pubs/surv-manual/chpt15-crs.html. Accessed on Jan 5, 2017
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Lambert N, Strebel P, Orenstein W, Icenogle J, Poland GA (2015). "Rubella". Lancet. 385 (9984): 2297–307. doi:10.1016/S0140-6736(14)60539-0. PMC 4514442. PMID 25576992.
- ↑ 5.0 5.1 5.2 5.3 Bouthry E, Picone O, Hamdi G, Grangeot-Keros L, Ayoubi JM, Vauloup-Fellous C (2014). "Rubella and pregnancy: diagnosis, management and outcomes". Prenat. Diagn. 34 (13): 1246–53. doi:10.1002/pd.4467. PMID 25066688.
- ↑ Lee JY, Bowden DS (2000). "Rubella virus replication and links to teratogenicity". Clin. Microbiol. Rev. 13 (4): 571–87. PMC 88950. PMID 11023958.
- ↑ Adamo MP, Zapata M, Frey TK (2008). "Analysis of gene expression in fetal and adult cells infected with rubella virus". Virology. 370 (1): 1–11. doi:10.1016/j.virol.2007.08.003. PMC 2694049. PMID 17920097.
- ↑ 8.0 8.1 Neu N, Duchon J, Zachariah P (2015). "TORCH infections". Clin Perinatol. 42 (1): 77–103, viii. doi:10.1016/j.clp.2014.11.001. PMID 25677998.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 Ajij M, Nangia S, Dubey BS (2014). "Congenital rubella syndrome with blueberry muffin lesions and extensive metaphysitis". J Clin Diagn Res. 8 (12): PD03–4. doi:10.7860/JCDR/2014/10271.5293. PMC 4316306. PMID 25654000.
- ↑ "Three cases of congenital rubella syndrome in the postelimination era--Maryland, Alabama, and Illinois, 2012". MMWR Morb. Mortal. Wkly. Rep. 62 (12): 226–9. 2013. PMID 23535689.
- ↑ WHO (2012). "Surveillance Guidelines for Measles, Rubella and Congenital Rubella Syndrome in the WHO European Region". PMID 23762964.
- ↑ U.S. Preventive Services Task Force https://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=congenital+rubella+syndrome. Accessed on Jan 17, 2017.
- ↑ Webster WS (1998). "Teratogen update: congenital rubella". Teratology. 58 (1): 13–23. doi:10.1002/(SICI)1096-9926(199807)58:1<13::AID-TERA5>3.0.CO;2-2. PMID 9699240.
- ↑ JOHNSON RE, HALL AP (1958). "Rubella arthritis; report of cases studied by latex tests". N. Engl. J. Med. 258 (15): 743–5. doi:10.1056/NEJM195804102581506. PMID 13541651.
- ↑ Cooper LZ (1985). "The history and medical consequences of rubella". Rev. Infect. Dis. 7 Suppl 1: S2–10. PMID 3890105.
- ↑ Banatvala JE, Brown DW (2004). "Rubella". Lancet. 363 (9415): 1127–37. doi:10.1016/S0140-6736(04)15897-2. PMID 15064032.
- ↑ Cooper LZ, Ziring PR, Ockerse AB, Fedun BA, Kiely B, Krugman S (1969). "Rubella. Clinical manifestations and management". Am. J. Dis. Child. 118 (1): 18–29. PMID 5815335.
- ↑ 18.0 18.1 18.2 18.3 Bullens D, Smets K, Vanhaesebrouck P (2000). "Congenital rubella syndrome after maternal reinfection". Clin Pediatr (Phila). 39 (2): 113–6. PMID 10696549.
- ↑ 19.0 19.1 19.2 Yazigi A, De Pecoulas AE, Vauloup-Fellous C, Grangeot-Keros L, Ayoubi JM, Picone O (2017). "Fetal and neonatal abnormalities due to congenital rubella syndrome: a review of literature". J. Matern. Fetal. Neonatal. Med. 30 (3): 274–278. doi:10.3109/14767058.2016.1169526. PMID 27002428.
- ↑ Morgan-Capner P, Hodgson J, Hambling MH, Dulake C, Coleman TJ, Boswell PA, Watkins RP, Booth J, Stern H, Best JM (1985). "Detection of rubella-specific IgM in subclinical rubella reinfection in pregnancy". Lancet. 1 (8423): 244–6. PMID 2857319.
- ↑ Ho-Terry L, Terry GM, Londesborough P, Rees KR, Wielaard F, Denissen A (1988). "Diagnosis of fetal rubella infection by nucleic acid hybridization". J. Med. Virol. 24 (2): 175–82. PMID 3351485.
- ↑ Terry GM, Ho-Terry L, Warren RC, Rodeck CH, Cohen A, Rees KR (1986). "First trimester prenatal diagnosis of congenital rubella: a laboratory investigation". Br Med J (Clin Res Ed). 292 (6525): 930–3. PMC 1339854. PMID 3083942.
- ↑ Valente P, Sever JL (1994). "In utero diagnosis of congenital infections by direct fetal sampling". Isr. J. Med. Sci. 30 (5–6): 414–20. PMID 8034496.
- ↑ Bosma TJ, Corbett KM, O'Shea S, Banatvala JE, Best JM (1995). "PCR for detection of rubella virus RNA in clinical samples". J. Clin. Microbiol. 33 (5): 1075–9. PMC 228107. PMID 7615708.
- ↑ Tipples GA, Hamkar R, Mohktari-Azad T, Gray M, Ball J, Head C, Ratnam S (2004). "Evaluation of rubella IgM enzyme immunoassays". J. Clin. Virol. 30 (3): 233–8. doi:10.1016/j.jcv.2003.11.006. PMID 15135741.
- ↑ Andrews N, Pebody RG, Berbers G, Blondeau C, Crovari P, Davidkin I, Farrington P, Fievet-Groyne F, Gabutti G, Gerike E, Giordano C, Hesketh L, Marzec T, Morgan-Capner P, Osborne K, Pleisner AM, Raux M, Tischer A, Ruden U, Valle M, Miller E (2000). "The European Sero-Epidemiology Network: standardizing the enzyme immunoassay results for measles, mumps and rubella". Epidemiol. Infect. 125 (1): 127–41. PMC 2869578. PMID 11057968.
- ↑ Bosma TJ, Corbett KM, Eckstein MB, O'Shea S, Vijayalakshmi P, Banatvala JE, Morton K, Best JM (1995). "Use of PCR for prenatal and postnatal diagnosis of congenital rubella". J. Clin. Microbiol. 33 (11): 2881–7. PMC 228600. PMID 8576339.
- ↑ Best JM, O'Shea S, Tipples G, Davies N, Al-Khusaiby SM, Krause A, Hesketh LM, Jin L, Enders G (2002). "Interpretation of rubella serology in pregnancy--pitfalls and problems". BMJ. 325 (7356): 147–8. PMC 1123673. PMID 12130613.
- ↑ 29.0 29.1 Radiopedia.org https://radiopaedia.org/articles/microcephaly. Accessed on Jan 17, 2017
- ↑ Morgan-Hughes GJ, Marshall AJ, Roobottom C (2003). "Morphologic assessment of patent ductus arteriosus in adults using retrospectively ECG-gated multidetector CT". AJR Am J Roentgenol. 181 (3): 749–54. doi:10.2214/ajr.181.3.1810749. PMID 12933475.
- ↑ Oster ME, Riehle-Colarusso T, Correa A (2010). "An update on cardiovascular malformations in congenital rubella syndrome". Birth Defects Res. Part A Clin. Mol. Teratol. 88 (1): 1–8. doi:10.1002/bdra.20621. PMID 19697432.
- ↑ Cordier AG, Vauloup-Fellous C, Grangeot-Keros L, Pinet C, Benachi A, Ayoubi JM, Picone O (2012). "Pitfalls in the diagnosis of congenital rubella syndrome in the first trimester of pregnancy". Prenat. Diagn. 32 (5): 496–7. doi:10.1002/pd.2943. PMID 22495555.
- ↑ Cofre F, Delpiano L, Labraña Y, Reyes A, Sandoval A, Izquierdo G (2016). "[TORCH syndrome: Rational approach of pre and post natal diagnosis and treatment. Recommendations of the Advisory Committee on Neonatal Infections Sociedad Chilena de Infectología, 2016]". Rev Chilena Infectol (in Spanish; Castilian). 33 (2): 191–216. doi:10.4067/S0716-10182016000200010. PMID 27314998.
- ↑ Radiopedia.org https://radiopaedia.org/articles/patent-ductus-arteriosus. Accessed on Jan 17, 2017
- ↑ Russell HC, McDougall V, Dutton GN (2011). "Congenital cataract". BMJ. 342: d3075. PMID 21622506.
- ↑ Lloyd IC, Goss-Sampson M, Jeffrey BG, Kriss A, Russell-Eggitt I, Taylor D (1992). "Neonatal cataract: aetiology, pathogenesis and management". Eye (Lond). 6 ( Pt 2): 184–96. doi:10.1038/eye.1992.37. PMID 1624043.