{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T15:14:15Z","timestamp":1772205255006,"version":"3.50.1"},"reference-count":65,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T00:00:00Z","timestamp":1407196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["U66IP000519"],"award-info":[{"award-number":["U66IP000519"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Risk Analysis"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>Although most infections with the rubella virus result in relatively minor <jats:italic>sequelae<\/jats:italic>, rubella infection in early pregnancy may lead to severe adverse outcomes for the fetus. First recognized in 1941, congenital rubella syndrome (CRS) can manifest with a diverse range of symptoms, including congenital cataracts, glaucoma, and cardiac defects, as well as hearing and intellectual disability. The gestational age of the fetus at the time of the maternal rubella infection impacts the probability and severity of outcomes, with infection in early pregnancy increasing the risks of spontaneous termination (miscarriage), fetal death (stillbirth), birth defects, and reduced survival for live\u2010born infants. Rubella vaccination continues to change the epidemiology of rubella and CRS globally, but no models currently exist to evaluate the economic benefits of rubella management. This systematic review provides an overall assessment of the weight of the evidence for the outcomes associated with rubella infections in the first 20 weeks of pregnancy. We identified, evaluated, and graded 31 studies (all from developed countries) that reported on the pregnancy outcomes of at least 30 maternal rubella infections. We used the available evidence to estimate the increased risks of spontaneous termination, fetal death, infant death, and CRS as a function of the timing of rubella infection in pregnancy and decisions about induced termination. These data support the characterization of the disability\u2010adjusted life years for outcomes associated with rubella infection in pregnancy. We find significant impacts associated with maternal rubella infections in early pregnancy, which economic analyses will miss if they only focus on live births of CRS cases. Our estimates of fetal loss from increased induced terminations due to maternal rubella infections provide context that may help to explain the relatively low numbers of observed CRS cases per year despite potentially large burdens of disease. Our comprehensive review of the weight of the evidence of all pregnancy outcomes demonstrates the importance of including all outcomes in models that characterize rubella\u2010related disease burdens and costs.<\/jats:p>","DOI":"10.1111\/risa.12264","type":"journal-article","created":{"date-parts":[[2014,8,5]],"date-time":"2014-08-05T23:20:57Z","timestamp":1407280857000},"page":"1315-1331","source":"Crossref","is-referenced-by-count":87,"title":["Characterization of the Risks of Adverse Outcomes Following Rubella Infection in Pregnancy"],"prefix":"10.1111","volume":"36","author":[{"given":"Kimberly M.","family":"Thompson","sequence":"first","affiliation":[{"name":"Kid Risk, Inc  10524 Moss Park Road, Ste. 204\u2010364 Orlando FL 32832 USA"},{"name":"University of Central Florida College of Medicine  Orlando FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily A.","family":"Simons","sequence":"additional","affiliation":[{"name":"Kid Risk, Inc  10524 Moss Park Road, Ste. 204\u2010364 Orlando FL 32832 USA"},{"name":"Harvard Medical School  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamran","family":"Badizadegan","sequence":"additional","affiliation":[{"name":"University of Central Florida College of Medicine  Orlando FL USA"},{"name":"Nemours Children's Hospital  Orlando FL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan E.","family":"Reef","sequence":"additional","affiliation":[{"name":"Centers for Disease Control and Prevention  Atlanta GA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis Z.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Columbia University School of Medicine  New York City NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,8,5]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"688","volume-title":"Vaccines: Expert Consult","author":"Reef SE","year":"2012"},{"key":"e_1_2_6_3_1","first-page":"35","article-title":"Congenital cataract following German measles in the mother","volume":"3","author":"Gregg NM","year":"1941","journal-title":"Transactions of the Ophthalmological Society of Australia"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","unstructured":"SimonsEA Reef SE Cooper L Zimmerman L Thompson KM.Systematic review of the manifestations of congenital rubella syndrome 2014;36(7):1315\u20131331.","DOI":"10.1111\/risa.12263"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268800048652"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268809991336"},{"key":"e_1_2_6_7_1","first-page":"1","article-title":"Rubella and other virus infections during pregnancy","volume":"101","author":"Manson MA","year":"1960","journal-title":"Ministry of Health Reports on Public Health and Medical Subjects"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(75)80119-3"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2005.01.014"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0022172400063452"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(199807)58:1<13::AID-TERA5>3.0.CO;2-2"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1135(83)90048-2"},{"issue":"3","key":"e_1_2_6_13_1","first-page":"445","article-title":"Congenital rubella in the USSR","volume":"57","author":"Kantorovic RA","year":"1979","journal-title":"Bulletin of the World Health Organization"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)92677-0"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-111-27750"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-111-27749"},{"key":"e_1_2_6_17_1","first-page":"349","article-title":"The impact of rubella epidemics on pregnant women, proof for the necessity of pre\u2010marital screening and vaccination","volume":"43","author":"Fogel A","year":"1979","journal-title":"Developments in Biological Standardization"},{"issue":"2","key":"e_1_2_6_18_1","first-page":"133","article-title":"Subclinical rubella in pregnancy\u2014Occurrence and outcome","volume":"21","author":"Fogel A","year":"1985","journal-title":"Israel Journal of Medical Sciences"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.299.6702.773"},{"issue":"2","key":"e_1_2_6_20_1","first-page":"26","article-title":"Rubella: A serologic study in pregnant women at Ramathibodi Hospital (1984\u20131985)","volume":"71","author":"Phiromsawat S","year":"1988","journal-title":"Journal of the Medical Association of Thailand"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00145421"},{"issue":"3","key":"e_1_2_6_22_1","first-page":"415","article-title":"Prenatal diagnosis of congenital rubella infection from maternal rubella in Taiwan","volume":"84","author":"Hwa HL","year":"1994","journal-title":"Obstetrics & Gynecology"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2005.09.007"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1957.02980240033009"},{"issue":"1","key":"e_1_2_6_25_1","doi-asserted-by":"crossref","first-page":"881","DOI":"10.5694\/j.1326-5377.1961.tb69287.x","article-title":"Congenital malformations and maternal rubella: Progress report","volume":"48","author":"Pitt DB","year":"1961","journal-title":"Medical Journal of Australia"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9378(66)90322-X"},{"issue":"1","key":"e_1_2_6_27_1","first-page":"95","article-title":"Congenital abnormalities following gestational rubella in Chinese","volume":"202","author":"Grayston JT","year":"1967","journal-title":"Journal of the American Medical Association"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.5332.711"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1965.02090030415009"},{"issue":"1","key":"e_1_2_6_30_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/oxfordjournals.aje.a112204","article-title":"Serologic studies in 11,460 pregnant women during the 1972 rubella epidemic in Israel","volume":"103","author":"Fogel A","year":"1976","journal-title":"American Journal of Epidemiology"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.3109\/inf.1980.12.issue-1.01"},{"issue":"1","key":"e_1_2_6_32_1","first-page":"46","article-title":"Rubella in pregnant Danish women 1975\u20131984","volume":"34","author":"Bitsch M","year":"1987","journal-title":"Danish Medical Bulletin"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(88)92249-0"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.3109\/inf.1983.15.issue-4.01"},{"issue":"1","key":"e_1_2_6_35_1","first-page":"65","article-title":"Outcome of pregnancy in a rubella outbreak in northern Ireland 1978\u20131979","volume":"53","author":"Connolly JH","year":"1984","journal-title":"Ulster Medical Journal"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/INF.0b013e3181a3e2d5"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447-0756.2010.01277.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1952.tb17855.x"},{"issue":"2","key":"e_1_2_6_39_1","first-page":"85","article-title":"Studies in congenital rubella, Baltimore 1964\u20131965 I: Epidemiologic and virologis","volume":"118","author":"Monif GH","year":"1966","journal-title":"Bulletin of the Johns Hopkins Hospital"},{"issue":"11","key":"e_1_2_6_40_1","doi-asserted-by":"crossref","first-page":"201","DOI":"10.5694\/j.1326-5377.1943.tb88413.x","article-title":"Congenital defects in infants following infectious diseases during pregnancy","volume":"11","author":"Swan CT","year":"1943","journal-title":"Medical Journal of Australia"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.37.10.1328"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(16)36734-5"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1949.02900500018005"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9378(15)33437-2"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1961.03040460019004"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(65)80196-2"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.3.5566.633"},{"issue":"5","key":"e_1_2_6_48_1","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1542\/peds.64.5.620","article-title":"Impaired cell\u2010mediated immune response in patients with congenital rubella: Correlation with gestational age at time of infection","volume":"64","author":"Buimovici\u2010Klein E","year":"1979","journal-title":"Pediatrics"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2004-1915"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.2307\/3348609"},{"key":"e_1_2_6_51_1","first-page":"86","article-title":"On the methodology of measuring the probability of fetal death in a prospective study","volume":"36","author":"Taylor WF","year":"1964","journal-title":"Human Biology"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-199101000-00006"},{"issue":"13","key":"e_1_2_6_53_1","first-page":"1","article-title":"Abortion surveillance\u2014United States, 2005","volume":"57","author":"Gamble SB","year":"2008","journal-title":"MMWR Surveillance Summaries"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/7.Supplement_1.S22"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1965.03080100061013"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.2307\/621855"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1973.00780020240004"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(67)80002-7"},{"issue":"1","key":"e_1_2_6_59_1","first-page":"1","article-title":"Virus diseases in pregnancy and congenital defects","volume":"12","author":"Hill AB","year":"1958","journal-title":"British Journal of Preventive and Social Medicine"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.64.9.1280"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61786-8"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpedi.1969.02100040020004"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/280455a0"},{"key":"e_1_2_6_64_1","volume-title":"Harvard School of Public Health, World Health Organization, World Bank. The global burden of disease: A comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020","author":"Murray CJL","year":"1996"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61680-8"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e31823fe923"}],"container-title":["Risk Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Frisa.12264","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/risa.12264","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T15:45:05Z","timestamp":1694619905000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/risa.12264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,5]]},"references-count":65,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1111\/risa.12264"],"URL":"https:\/\/doi.org\/10.1111\/risa.12264","archive":["Portico"],"relation":{},"ISSN":["0272-4332","1539-6924"],"issn-type":[{"value":"0272-4332","type":"print"},{"value":"1539-6924","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,5]]}}}