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2005 CMA Media Inc. or its licensors

Congenital rubella syndrome despitematernal antibodies

Although congenital rubellasyndrome (Box 1) is rarein Canada, it does still occur.Many wo me n im mi gr at e to

Canada from countries withouta rubella vaccination programand may not have adequate im-munity. In 2002, only 124(58%) of 214 countries or terri-

tories around the world had im-plemented a rubella vaccinationprogram.1 An Australian studyfound that women born in Asia,

sub-Saharan Africa and SouthAmerica were 5 times as likely asother women to be seronegativefor rubella virus. In a review ofall cases of infants with congeni-tal rubella syndrome in theUnited States reported to theNational Congenital RubellaSyndrome Registry from 1997to 1999, 83% (20/24) were bornto Hispanic mothers and 91%(21/23) were born to foreign-born mothers.

Sri Lanka does not have a

rubella vaccination program;therefore, if our patients lowpositive titre from 1993 was atrue-positive result, it was likelythe result of natural immunity.Since serologic testing for rubellawas documented only once pre-ceding this pregnancy, westrongly suspect, but cannot con-firm, that this case of congenitalrubella syndrome resulted from

rubella reinfection: the IgG titrehad increased markedly, from17 IU/mL in 1993 to 281 IU/mL10 years later, with a positive IgM

titre and no history of revaccina-tion. A rubella-specific IgM testperformed at 12 weeks gestationwould have confirmed infectionrather than immunity.

Numerous cases of congeni-tal rubella syndrome due torubella reinfection have been re-ported.2All involved exposure torubella in the first trimester ofpregnancy after both naturaland vaccine-induced immunity,usually with subclinical infectionin the mother. The immune re-

sponse may involve more thanhumoral immunity, but it isclear that rubella antibodies de-cline over time and may increasethe risk of reinfection. In a studyinvolving Korean children,18.8% of those who had beenvaccinated and 13.8% of thosewi th na tura l im muni ty werefound to be seronegative forrubella virus after 3 years. An

TEACHING CASE REPORT

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THE CASE: In January 2004 a female infant was delivered by cesarean section at 36 weeks gestationbecause of severe intrauterine growth restriction. The mother was a healthy 31-year-old gravida 4para 2 woman who had been travelling in Sri Lanka from before conception until 6 weeks gesta-tion. Blood drawn for antenatal tests at 6 weeks gestation upon her return to Canada was not ini-tially tested for rubella titre. A rubella titre at 12 weeks gestation (425 IU/mL) was interpreted asindicating immunity. The pregnancy was uncomplicated, without a history of fever or rash.

The mother had immigrated to Canada from Sri Lanka in 1993, at which point her rubella titrehad been 17 IU/mL. She did not recall a history of rubella infection or of rubella vaccination. She haddelivered a healthy child in 1996, but rubella screening had not been requested during that preg-nancy. In her other 2 pregnancies, which did not carry to term, her rubella titre had not been tested.

Findings on initial physical examination of the daughter born in 2004 were unremarkable. Herbirth weight was 1.58 kg, head circumference 28.3 cm and length 41 cm (all below the third per-centile). Hematologic studies revealed a normal leukocyte count and hemoglobin concentration buta low platelet count (49 109/L). During the first few days, the infant had hypoglycemia, hypocal-cemia and hyponatremia, with a single seizure being attributed to hyponatremia. Ultrasonographyof the head yielded normal findings. A murmur was noted on day 3 of life, and echocardiographydemonstrated a large patent ductus arteriosis, a patent foramen ovale and severe pulmonary valvu-

lar stenosis. The infant was subsequently given a diagnosis of bilateral congenital cataracts.On the first day of the infants life, her rubella IgG titre was 243 IU/mL (immunity is indicatedat a titre of 1015 IU/mL or greater) and the rubella IgM titre was 1.123 index units (a positive re-sult is 0.3 or more index units [Behring Enzygnost, Behring Diagnostics, Marburg, Germany]).Rubella virus was cultured from the urine and from both extracted cataracts.

After delivery, the stored antenatal serum that had been collected at 6 weeks gestation wastested, and the rubella IgG and IgM titres were both positive (281 IU/mL and 0.619 index units re-spectively). All rubella titres were performed at the Ontario Central Public Health Laboratory.

Key points

Consider rubella vaccination of nonpregnant im-migrant women at their first encounter with thehealth care system.

Women with a low positive IgG titre (e.g., 1015 IU/mL) before pregnancy may benefit from re-

peat rubella vaccination. Women should be screened for rubella susceptibil-

ity at each pregnancy, because immunity (from pre-vious vaccination or natural immunity) can wane.

If a pregnant woman with a low positive IgG titrehas recently been exposed to rubella, measure-ment of her IgM titre can help distinguish betweennew infection and immunity.

Seronegative pregnant women need to be givenrubella vaccine after delivery.

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Italian study showed that 9.8%of vaccinated girls were re-infected by wild-type rubellavirus within 5 years.

Prenatal serologic testing forrubella usually includes only theIgG titre, and the result is re-ported as immune or non-immune (Box 2). There is con-troversy over what level of titre

confers immunity. Bullens andcoauthors2 documented that 8 of16 mothers whose infants hadcongenital rubella syndromehad rubella IgG titres of at least15 IU/mL at the start of preg-nancy, a level considered to beprotective. Their finding ques-tions whether the current cutofflevel 1015 IU/mL is too low tobe considered protective andwhether women with low posi-tive rubella titres before preg-nancy might benefit from repeat

vaccination.

In the absence of quantitativeIgG reporting, clinicians do notknow which women have lowpositive titres. A further problemis that a single IgG titre withoutan IgM titre cannot differentiaterecent infection from immunity,as demonstrated by the case wehave reported. Processing allrubella serologic tests in a cen-

tralized laboratory with quanti-tative IgG titres may enable thedetection of significant rises inIgG levels in subsequent sam-ples. Rubella-specific IgM titrescould be routinely measuredduring the prenatal screening,but the cost-effectiveness of thisapproach would be questionable.

Given that more than half ofthe worlds population lives incountries without a rubella vacci-nation program, many newCanadians are susceptible to

rubella. Physicians should con-

sider offering measlesmumpsrubella vaccination to nonpreg-nant immigrant women from de-veloping countries at their firstcontact with the health care sys-tem.3 Serologic screening beforevaccination is not recommendedand may result in a missed op-portunity to vaccinate if preg-nancy occurs in the interim or if

the woman is lost to follow-up.Consultations before travel mayrepresent an opportunity to re-view rubella immunization statusof women of childbearing age.

Because rubella antibodieswane over time, screening forrubella susceptibility is recom-mended at the first prenatal visitfor all pregnant women inCanada. In a Canadian study,2.3%13.3% of pregnant womenwere seronegative for rubellavirus. A Quebec study found that

only half of the 8.4% womenwho were rubella seronegativereceived the vaccine after deliv-ery. Standing orders for rubellavaccination after delivery may in-crease immunization rates.

Anna BanerjiPublic Health SciencesUniversity of TorontoDepartment of PediatricsSt. Josephs Health CentreToronto, Ont.Elizabeth Lee Ford-JonesDivision of Infectious DiseasesHospital for Sick ChildrenToronto, Ont.Edmond KellyDepartment of PediatricsMount Sinai HospitalToronto, Ont.Joan Louise RobinsonDepartment of PediatricsStollery Childrens HospitalEdmonton, Alta.

References1. Robertson SE, Featherstone DA,

Gacic-Dobo M, Hersh BS. Rubellaand congenital rubella syndrome:global update. Rev Panam Salud Pub-lica 2003;14(5):306-15.

2. Bullens D, Smets K, VanhaesebrouckP. Congenital rubella syndrome aftermaternal reinfection. Clin Pediatr2000;39(2):113-6.

3. Ford-Jones EL, Tam T, Kelly E, De-Serres G. Prevention of congenitalrubella syndrome. Statement of the In-fectious Disease and ImmunizationCommittee, Canadian Pediatric Society.

Paediatr Child Health 1999;4(2):155-7.

Box 2: Limitations of antenatal screening for rubella

Laboratories usually report result of serologic test for IgG titre asimmune (> 1015 IU/mL*) or nonimmune

Low or borderline IgG levels are not detected

Reinfection resulting in congenital rubella syndrome has occurred at

low levels of immunity Substantial rises in IgG levels (indicating possible infection) cannot

be detected without quantitative reporting

Measurement of the IgM titre is necessary to distinguish betweenimmunity and infection

Laboratories using the Abbott AxSym immunoassay system (Abbott Laboratories Canada,Mississauga, Ont.) consider a positive result to be 10 IU/mL or greater; most other laboratoriesconsider a positive result to be 15 IU/mL or greater.

Box 1: Clinical features of congenital rubella syndrome

Classic triad

Congenital heart disease(e.g., patent ductus arteriosis, pulmonaryartery stenosis, pulmonary valvular stenosis)

Ocular defects(e.g., congenital cateracts, microphthalmos,pigmentary retinopathy, congenital glaucoma)

Hearing loss

Congenital rubella syndrome is usually associated with a failure tothrive and developmental delay as well as microcephaly. Othercommon presentations at birth include:

purpuric rash hepatosplenomegaly meningoencephalitis radiolucent bone hepatitis thrombocytopenia