Test Uptake and Case Detection of Syphilis, HIV, and Hepatitis C Among Women Undergoing Prenatal Screening in British Columbia, 2007 to 2011

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1 OBSTETRICS Test Uptake ad Case Detectio of Syphilis, HIV, ad Hepatitis C Amog Wome Udergoig Preatal Screeig i British Columbia, 2007 to 2011 Margot Kuo, MPH, 1 Deborah M. Moey, MD, FRCSC, 2,3 Maria Alvarez, MSc, 1 Jae A. Buxto, MBBS, MHSc, FRCPC, 1,4 Mel Krajde, MD, FRCPC, 1,5 Richard T. Lester, MD, FRCPC, 1,6 Gia Ogilvie, MD, FCFP, DrPH, 1,7 Mark Gilbert, MD, MHSc, FRCPC 1,4 1 British Columbia Cetre for Disease Cotrol, Vacouver BC 2 Departmet of Obstetrics ad Gyaecology, Uiversity of British Columbia, BC Wome s Hospital, Vacouver BC 3 Wome s Health Research Istitute, Vacouver BC 4 School of Populatio ad Public Health, Uiversity of British Columbia, Vacouver BC 5 Departmet of Pathology ad Laboratory Medicie, Uiversity of British Columbia, Vacouver BC 6 Departmet of Medicie, Divisio of Ifectious Diseases, Uiversity of British Columbia, Vacouver BC 7 Faculty of Medicie, Uiversity of British Columbia, Vacouver BC Abstract Objective: Test uptake ad case detectio treds for rubella, syphilis, HIV, ad hepatitis C (HCV) were compared amog the 2007 to 2011 cohort of wome udergoig preatal testig i British Columbia. Aalysis ivolved likage of provicially cetralized laboratory ad surveillace data to assess preatal test uptake ad rates of ewly diagosed versus prevalet ifectios. Methods: We icluded preatal specimes submitted from BC wome aged 16 to 45 years i 2007 to Laboratory records were liked to provicial surveillace systems to idetify cofirmed materal syphilis ad HIV cases. Previous positive status was determied for HIV ad HCV if a prior cofirmed case was idetified from laboratory records. We determied rates of HIV ad HCV ewly idetified at preatal screeig (ew diagoses per per year). Prevalece for HIV ad HCV was the sum of all ew ad prior diagoses (prevalece per per year). Results: Of wome, 96.9% were screeed for rubella, 93.3% for syphilis, 93.8% for HIV, ad 21.5% for HCV. From 2007 to 2011, the overall rates of ew diagoses were 15.4, 5.1, ad 82.8 cases per per year for syphilis, HIV, ad HCV, Key Words: Rubella, syphilis, HIV, hepatitis C, preatal, prevalece, screeig, data likage Competig Iterests: Noe declared Received o September 26, 2013 Accepted o Jauary 9, 2014 respectively. The overall prevalece was 45.9 ad cases per per year for HIV ad HCV, respectively (0.05% ad 0.6%). From 2007 to 2011, ew diagoses of HCV decreased 40% from to 62.1 cases per per year. HCV prevalece did ot chage ad icreased with materal age. Coclusio: This study liks surveillace ad laboratory data to provide a provicial picture of preatal screeig test uptake ad case detectio, with the advatage of distiguishig ew from prior diagoses. This iformatio ca help guide preatal commuicable disease screeig policy. Résumé Objectif : La mesure das laquelle les tests de dépistage de la rubéole, de la syphilis, du VIH et de l hépatite C (VHC) ot été utilisés et les tedaces e ce qui cocere la détectio de cas de ces maladies ot été comparées, etre 2007 et 2011, chez les cohortes de femmes faisat l objet d u dépistage préatal e Colombie-Britaique. L aalyse a mis e jeu le croisemet de doées de surveillace et de laboratoire cetralisées à l échelle proviciale, afi de détermier la mesure das laquelle les tests de dépistage préatal ot été utilisés et de comparer le taux d ifectios ouvellemet diagostiquées au taux d ifectios prévaletes. Méthodes : Nous avos iclus les prélèvemets préataux, issus de Britao-colombiees âgées de 16 à 45 as, qui ot été soumis au cours de la période allat de 2007 à Les dossiers de laboratoire ot été liés aux systèmes de surveillace proviciaux e vue d idetifier les cas materels cofirmés de 482 JUNE JOGC JUIN 2014

2 Test Uptake ad Case Detectio of Syphilis, HIV, ad Hepatitis C Amog Wome Udergoig Preatal Screeig syphilis et de VIH. La présece d u statut de séropositivité préalable a été établie, pour ce qui est du VIH et du VHC, e ce qui cocere les cas préalablemet cofirmés ayat été idetifiés à partir des dossiers de laboratoire. Nous avos détermié les taux d ifectios au VIH et au VHC ouvellemet idetifiées au momet du dépistage préatal (ouveaux diagostics par par aée). La prévalece du VIH et du VHC équivalait à la somme de tous les diagostics, tat ouveaux que préalables (prévalece par par aée). Résultats : Chez femmes, 96,9 % ot fait l objet d u dépistage visat la rubéole, 93,3 % ot fait l objet d u dépistage visat la syphilis, 93,8 % ot fait l objet d u dépistage visat le VIH et 21,5 % ot fait l objet d u dépistage visat le VHC. Etre 2007 et 2011, les taux globaux de ouveaux diagostics ot été de 15,4, de 5,1 et de 82,8 cas par par aée pour ce qui est de la syphilis, du VIH et du VHC, respectivemet. La prévalece globale était de 45,9 et de 551,5 cas par par aée pour ce qui est du VIH et du VCH, respectivemet (0,05 % et 0,6 %). Etre 2007 et 2011, les ouveaux diagostics de VHC ot cou ue baisse de 40 % e passat de 106,0 à 62,1 cas par par aée. La prévalece du VHC a pas cou de fluctuatio et ous avos costaté que celle des aticorps ati- VHC augmetait e foctio de l âge materel. Coclusio : Cette étude a procédé au croisemet des doées de surveillace et de laboratoire afi de pouvoir brosser u tableau provicial de la mesure das laquelle les tests de dépistage préatal ot été utilisés et de la détectio de cas qui s e est suivie, le tout s accompagat de l avatage de pouvoir distiguer les ouveaux diagostics des diagostics préalables. Ces reseigemets pourrot cotribuer à orieter la politique de dépistage préatal des maladies trasmissibles. J Obstet Gyaecol Ca 2014;36(6): INTRODUCTION The cotiuum of care ad testig that wome i British Columbia ca expect to receive at each stage of pregacy is outlied i a 2010 Periatal Services BC obstetrics guidelie, which icludes preatal commuicable disease screeig recommedatios. 1 Uiversal screeig meas offerig volutary screeig to as may people i the defied populatio as possible. 2 Rubella, syphilis, ad HIV testig is recommeded as part of uiversal preatal screeig i BC, while atibody testig for hepatitis C virus ifectio (ati-hcv), i keepig with Caadia guidelies, is targeted to wome presetig with HIV ad/or persistetly elevated alaie trasamiase at screeig, 1 3 ABBREVIATIONS BC EIA HAART HCV NAAT PHMRL RPR British Columbia ezyme immuoassay highly active atiretroviral therapy hepatitis C ucleic acid amplificatio testig BC Public Health Microbiology Referece Laboratory rapid plasma reagi as well as to wome with specific risk factors: a history of ijectio drug use, hemodialysis, receipt of blood products before 1992 or clottig factors before 1988, exposure to blood of a high-risk idividual, icarceratio. Testig for ati-rubella IgG is recommeded at preatal screeig to determie if a woma is susceptible to rubella ifectio that places the eoate at risk of cogeital rubella. Preatal screeig for rubella is well-established, with high uptake ad without the stigma that may be associated with syphilis, HIV, or HCV testig. Rubella screeig ca thus serve as a stadard for comparig the uptake of other tests. Testig for syphilis is recommeded i every pregacy, o the basis of evidece that uiversal preatal screeig for syphilis ifectio decreases adverse pregacy outcomes ad the proportio of ifats with cliical maifestatios of syphilis ifectio. 1,2,4 6 Uiversal preatal HIV testig has bee recommeded i BC sice to guide obstetric care ad the prevetio of periatal trasmissio. 1,2 Key ratioales for uiversal screeig for HIV have bee the growig prevalece of Caadia wome livig with HIV ad the effectiveess with which vertical trasmissio ca be preveted with ativiral treatmet. 2,5 British Columbia uses the opt-i strategy for preatal HIV testig; a woma must verbally coset to be HIV-tested. Uder a opt-out strategy, HIV testig is icluded as oe of the routie preatal tests, but a woma has the right to refuse ay of the tests. 8 From 2007 to 2011, BC s aual rate of reported HCV cases raged from 1.8 to 1.5 times higher tha the atioal rate, with rates i males twice those i females. 9 I BC from 2000 to 2002, 20% of wome uderwet ati-hcv testig at preatal screeig. 10 I a study of pregat wome i BC, Blasig et al. compared materal HCV prevalece determied by data likage to that derived from a seroprevalece survey. They demostrated HCV prevalece at preatal screeig is uderestimated by usig risk-based screeig, ad they recommeded further research to weigh risk-based versus uiversal screeig for HCV. 10 The BC Cetre for Disease Cotrol provides surveillace ad aual reportig of materal syphilis ad HIV. 11,12 We coducted a data likage betwee the surveillace ad laboratory databases to better describe test uptake, firsttime diagoses made at preatal screeig, ad aual prevalece amog wome screeed. Specifically, our aim was to uderstad the comparative test uptake ad treds for syphilis, HIV, ad HCV amog the 2007 to 2011 cohort of wome testig preatally. We calculated the icidece of ewly diagosed syphilis, HIV, or HCV at preatal screeig for each year ad the prevalece of HIV ad HCV amog this populatio (both previously ad ewly diagosed cases). JUNE JOGC JUIN

3 Obstetrics METHODS The BC Public Health Microbiology Referece Laboratory performs all rubella ad syphilis screeig, approximately 95% of all HIV screeig ad all cofirmatory HIV testig, ad 95% of all HCV atibody ad cofirmatory testig for the provice. This eables accurate determiatio of the provicial testig deomiator ad cofidece i the completeess of testig data used to determie ew diagoses ad prevalet cases. Routie preatal specimes (idetified based o preatal test storage codes) submitted from BC wome aged 16 to 45 betwee Jauary 1, 2007, ad December 31, 2011, were icluded i this retrospective aalysis. Patiet age ad Regioal Health Authority of residece were cocurretly extracted from electroic laboratory testig records (PHMRL). Testig records were extracted from the PHMRL ad duplicates removed. Specimes with missig results, missig or ivalid patiet likage idetifiers, idetified as laboratory proficiecy testig (i.e., ot a real patiet), or i which the test was cacelled were excluded. From 2007 to 2011, the umber of testig evets (sigle laboratory records) that could ot be liked raged betwee 1900 ad 2200 per year. The total umber of records per year raged betwee ad Multiple records of the same idividual were collapsed ito a sigle patiet-cetric record (from oe lie per test to oe lie per patiet) based o patiet idetifiers ad specime collectio dates. Flags were created for all relevat tests ad preatal status based o specime codes. Eligible preatal test records were liked usig persoal idetifiers (ame, date of birth, ad persoal health umber) to the provicial HIV ad sexually trasmitted ifectio surveillace systems to idetify cofirmed HIV ad materal syphilis cases. Previous positive status was determied for HIV ad HCV if the woma had bee reported as a case before the date of the preatal test (usig the provicial HIV surveillace system ad PHMRL records, respectively). Likage to these historical data eabled assessmet of prior HIV ad HCV ifectio to determie if detected cases were ewly diagosed at screeig (ew diagoses per per year) or had bee previously idetified. HIV ad HCV prevalece were defied as the sum of all ew ad prior diagoses amog screeed wome (prevalece per per year). Rubella immue status was determied by ezyme-liked immuosorbet assay testig for the presece of IgG atibodies. Results were categorized ito three serostatus groups. Seropositive was reported for levels greater tha or equal to 10 IU/mL, the accepted threshold of rubella immuity; equivocal was reported for values betwee 5.0 ad 9.9 IU/mL; ad seroegative was reported for values less tha 5.0 IU/mL. Materal syphilis cases were idetified usig a rapid plasma reagi screeig test ad, if positive, were cofirmed usig Trepoema pallidum particle agglutiatio ad/or fluorescet trepoemal atibody absorptio tests. Alteratively, darkfield microscopy ad ucleic acid amplificatio testig was used to cofirm syphilis ifectio. Syphilis diagosed from the preatal screeig specime was cosidered a ew diagosis. HIV cases were defied through detectio of HIV atibody by a screeig ezyme-liked immuosorbet assay (third geeratio), followed by a cofirmatory test (Wester Blot ad/or NAAT or a positive NAAT or p24 atige [cofirmed by eutralizatio assay]). Positive tests for HIV at the time of preatal screeig were cofirmed as ewly diagosed or a repeat positive usig a combiatio of laboratory ad surveillace data sources (the BC HIV surveillace system ad PHMRL). HCV cases were defied through detectio of atibodies to HCV (ati-hcv) by a third geeratio ezyme immuoassay. If the iitial scree was positive, the specime was retested by a differet maufacturer s third geeratio EIA. Oly specimes positive by both maufacturers tests were cosidered to be ati-hcv positive. Ati- HCV positive tests at the time of preatal screeig were cofirmed as ewly diagosed or previously diagosed cases usig laboratory data (PHMRL). HCV-RNA testig is ot routiely performed o all ati-hcv positive cases; thus, the umber of active HCV ifectios amog cases i this aalysis may be overestimated by approximately 25% to 30%, although clearace rates up to 40% have bee observed amog youg females. 13 Specime data were cosolidated ito a sigle record for each woma udergoig at least oe preatal test i a give caledar year. If a woma had multiple testig episodes withi a caledar year, the most recet specime results were used. Uptake of testig was evaluated by the year of specime collectio; thus, testig for each ifectio (rubella, syphilis, HIV, HCV) was couted oce for each woma i a give year. Similarly, age ad reactive status were couted oce for each woma i a give year. Thus, all wome i the aalysis i a give caledar year were uique, but idividual wome could repeat across years. Rubella serostatus was compared by age ad the year the specime was collected. A hierarchy was used to determie serostatus for a give year for each woma: wome were cosidered to be seropositive i a give year if a positive test result was recorded at ay time regardless of the 484 JUNE JOGC JUIN 2014

4 Test Uptake ad Case Detectio of Syphilis, HIV, ad Hepatitis C Amog Wome Udergoig Preatal Screeig other test results. I the evet that two or more test results idicated equivocal ad o-reactive, equivocal was assiged. Wome were categorized as o-reactive oly if all test results were o-reactive. Test uptake was the percetage of wome tested each year. New diagosis rates were calculated for HIV, HCV, ad syphilis cases. The rates of ew diagosis were calculated by dividig the umber of ew diagoses at preatal screeig i a particular year by the total umber of idividual wome udergoig preatal screeig i that year. Comparisos were made across age groups ad years. Prevalece was determied for HIV ad HCV oly; comparisos across age groups ad study years were coducted. Prevalece was calculated by dividig the total umber of both ew ad previously positive cases i a particular year by the total umber of wome who submitted a preatal sample i that year. Amog wome previously diagosed with HIV ad HCV, we report the proportio who subsequetly re-tested at a later preatal scree. Categorical data were aalyzed usig Pearso s chi-square (Fisher exact i the case of 20% of expected cell cout less tha 5); treds were evaluated by Cochra-Armitage tred test (prop.tred.test i R); P 0.05 was cosidered statistically sigificat. Statistical aalyses were performed usig SPSS versio 14.0 (IBM Corp., Armok, NY) ad R statistical package 2012 (R Foudatio, Viea, Austria). BC Cetre for Disease Cotrol i partership with PHMRL has the legal authority, uder the BC Public Health Act, to steward ad lik laboratory ad surveillace data for commuicable disease surveillace, ad a madate to coduct public health evaluatios. Ethics approval was therefore ot required. RESULTS Betwee Jauary 1, 2007, ad December 31, 2011, specimes were submitted to the PHMRL for preatal screeig from wome. A total of idividual wome were screeed durig the five-year study period: (75.1%) tested i oly oe year, (22.0%) tested i two years, ad 5323 (2.9%) tested i three or more years. Of the wome who uderwet oe or more preatal screes i the study period, 96.9% were screeed for rubella, 93.3% for syphilis, 93.8% for HIV, ad 21.5% for HCV. Over the five years, there was a tred of icreased uptake of rubella, syphilis, HIV, ad HCV screeig (Tables 1 ad 2). As expected, rubella testig had the highest uptake: 96.0% i 2007 to 97.0% i 2011 (P for icreasig tred < 0.001). Syphilis testig icreased from 91.1% i 2007 to 95.5% i 2011 (P for tred < 0.001). HIV testig icreased from 91.6% i 2007 to 95.9% i 2011 (P for tred < 0.001). HCV testig icreased from 17.6% i 2007 to 25.9% i 2011 (P for tred < 0.001). Test uptake for rubella, syphilis, ad HIV were highest amog youger age groups ad lowest amog 41 to 45 year olds. HCV test uptake, o the other had, was 22.9% i the yougest age group to a high of 28.6% i the oldest group. I geeral, test uptake amog wome over 40 years versus uptake i wome 40 years ad youger showed the most otable differeces, with lower uptake for rubella, syphilis, ad HIV but higher uptake for HCV i the oldest age group. Seropositivity for rubella icreased by 1.7% over the study period, with a correspodig decrease i the umber of wome with equivocal (0.9%) ad seroegative (0.8%) results (Table 2). I 2011, 95% of wome tested were seropositive for atibody to rubella virus. Seropositivity for rubella icreased across age groups from 87.7% amog 16- to 20-year-olds to 95% or greater amog 36- to 45-yearolds (P for tred < 0.001). Correspodigly, equivalecy ad seroegativity decreased across age groups (P for tred < 0.001). A tred of sigificatly decreasig seroegativity from youger to older wome was observed (5.0% i wome aged 16 to 20 years to 3.0% i wome aged 41 to 45 years, P < 0.001). There were 36 ewly diagosed cases of syphilis across the five-year study period (Table 2). The overall syphilis diagosis rate was 15.4 cases per per year. Syphilis diagosis rates varied over the five-year period ad, while there was o statistically sigificat tred, 2010 ad 2011 had the lowest rates at 10.8 ad 4.3 cases per, respectively. The highest diagosis rates were amog the yougest ad oldest age groups (16- to 20-year-olds ad 41- to 45-year-olds, at 26.8 ad 25.5 per per year, respectively); the lowest rates were amog 26- to 30-yearolds at 12.8 per per year. For HIV, there were 12 ew diagoses ad 107 prevalet cases over the five-year period (Table 1). The overall ew diagosis rate was 5.1 cases per per year. This raged from 0 to 13 cases per per year, with o tred detected. Overall HIV prevalece (prevalet plus ew diagoses) was 45.9 cases per per year (0.05%), with o statistically sigificat differeces i aual prevalece. Amog wome who had a prior HIV diagosis o record, 41.1% were retested for HIV at a subsequet preatal scree. JUNE JOGC JUIN

5 Obstetrics Table 1. Uptake of preatal screeig for HIV ad HCV, rates of ew diagoses, ad prevalece amog wome who have had preatal screeig, BC, 2007 to 2011 Year Total screeed (deomiator)* Total tested HIV New diagoses/ Prevalece/ Total tested HCV New diagoses/ Prevalece/ (91.6) 13.0 (6) 54.1 (25) 8127 (17.6) (49) (239) (92.6) 0.0 (0) 48.6 (23) 9293 (19.6) (50) (267) (93.7) 4.3 (2) 36.4 (17) (21.5) 64.2 (30) (256) (95.1) 6.5 (3) 41.1 (19) (22.7) 75.8 (35) (264) (95.9) 2.1 (1) 49.2 (23) (25.9) 62.1 (29) (260) Overall (93.8) 5.1 (12) 45.9 (107) (21.5) 82.8 (193) (1286) P for χ 2 < NS < NS P for tred < NS NS < NS Age group, years 16 to (95.5) 0.0 (0) 26.8 (3) 2557 (22.9) 62.6 (7) (32) 21 to (94.4) 16.4 (6) 54.6 (20) 7884 (21.5) (44) (206) 26 to (94.0) 1.4 (1) 38.5 (27) (20.4) 77.1 (54) (373) 31 to (93.4) 4.2 (3) 39.5 (28) (20.7) 70.5 (50) (363) 36 to (93.0) 2.7 (1) 54.7 (20) 8426 (23.0) 68.3 (25) (240) 41 to (92.7) 12.7 (1) (9) 2247 (28.6) (13) (70) P for χ 2 < < < P for tred < NS NS < NS < **The deomiator is total wome screeed (ay test with a preatal storage code) ad does ot represet those specifically screeed for HIV or HCV * Cochra-Armitage test for tred (oe-sided) Fisher exact test (performed if > 20% of cells with cell size < 5) or Cochra-Armitage test for tred (exact) New HIV diagosis rates across the age groups raged from 0.0 per per year i wome aged 16 to 20 to 16.4 per per year i wome aged 21 to 25 years. The tred aalysis across age groups was ot sigificat (P = 0.376) but there was sigificat variatio betwee the age groups (P = 0.039). HIV prevalece varied by age group (P = 0.040), ragig from 26.8 per per year i wome aged 16 to 20 years to per per year i wome aged 41 to 45 years, with o detectable treds by age (P = 0.113). There were 193 ati-hcv positive wome ewly diagosed at preatal testig, ad 1286 prevalet cases across the five years (Table 1). The overall HCV ew diagosis rate was 82.8 cases per per year, decreasig from per to 62.1 per betwee 2007 ad 2011, a reductio of 43.9 cases per (P for tred < 0.005). Overall HCV prevalece was cases per per year (0.6%), with o statistically sigificat chages i prevalece by year. Amog wome who had a prior positive ati-hcv test result o record, 38.5% were retested for atibody to HCV at a subsequet preatal scree. While there was sigificat variatio i rates of HCV ew diagosis by age groups, there was o tred detected (P = 0.585). The lowest was 62.6 per per year amog 16- to 20- year-olds, ad the highest was per amog 41- to 45-year-olds. Ati-HCV prevalece icreased over the rage from the yougest to the oldest age group, from per per year (0.3%) to per per year (0.9%), a differece of cases per per year (P for tred < 0.001). While age-specific rates of HIV ad HCV are highest i the oldest age group, this age group has the smallest umber of wome. The majority of ew diagoses of HIV ad HCV occur amog 21- to 35-year-olds, ad the majority of prevalet HIV ad HCV cases are amog 26- to 40-year-olds. DISCUSSION This study liked surveillace ad laboratory data to provide a provicial picture of preatal screeig uptake ad case detectio, with the advatage of distiguishig 486 JUNE JOGC JUIN 2014

6 Test Uptake ad Case Detectio of Syphilis, HIV, ad Hepatitis C Amog Wome Udergoig Preatal Screeig Table 2. Uptake of preatal screeig for syphilis ad rubella, syphilis diagosis rate, ad rubella serology results amog wome who have had preatal screeig, BC, 2007 to 2011 Year Total screeed (deomiator)* Total tested Syphilis Diagoses/ Total tested Rubella Rubella test results Seropositive Equivocal Seroegative (91.1) 15.1 (7) (96.0) (93.3) 1359 (3.1) 1614 (3.6) (92.2) 23.2 (11) (96.8) (93.9) 1316 (2.9) 1498 (3.3) (93.0) 23.5 (11) (97.4) (94.7) 1088 (2.4) 1320 (2.9) (94.3) 10.8 (5) (97.2) (94.8) 1156 (2.6) 1200 (2.7) (95.5) 4.3 (2) (97.0) (95.0) 989 (2.2) 1256 (2.8) Overall (93.3) 15.4 (36) (96.9) P for χ 2 < NS < < < < P for tred < NS < < < < Age group, years 16 to (94.5) 26.8 (3) (96.8) 9497 (87.7) 793 (7.3) 537 (5.0) 21 to (94.2) 19.1 (7) (97.4) (92.8) 1291 (3.6) 1277 (3.6) 26 to (94.0) 12.8 (9) (97.4) (94.7) 1600 (2.3) 2024 (3.0) 31 to (92.9) 14.1 (10) (96.9) (94.9) 1436 (2.1) 2040 (3.0) 36 to (91.9) 13.7 (5) (96.1) (95.9) 635 (1.8) 791 (2.2) 41 to (89.2) 25.5 (2) 7346 (93.6) 6974 (94.9) 153 (2.1) 219 (3.0) P for χ 2 < NS < < < < P for tred < NS < < < < **The deomiator is total wome screeed (ay test with a preatal storage code) ad does ot represet those specifically screeed for syphilis or rubella Cochra-Armitage test for tred (oe-sided) * Fisher exact test (performed if > 20% of cells with cell size < 5) or Cochra-Armitage test for tred (exact) ew from prior diagoses. Our results cofirm that preatal screeig uptake for rubella, syphilis, ad HIV testig is high ad improvig aually i BC. HCV test uptake is low but has icreased: 25.9% of wome tested for HCV i 2011, up from 17.6% i I BC, preatal screeig data are ot routiely collated ad moitored at a provicial level. This data likage represets a excellet opportuity to ehace surveillace quality ad utility by eablig quatificatio of provicial preatal test uptake ad case detectio treds. Its stregths iclude the ability to lik to prior testig results to idetify repeat ifectios for syphilis ad to cofirm ew or previously diagosed ifectio with HIV ad HCV. I the absece of comprehesive screeig surveillace, the data likage approach is a improvemet o usig diagosis rates aloe without prior testig history, ad provides a reasoable estimatio of HIV materal prevalece rates while beig less ivasive ad costly tha seroprevalece studies. Although there are methodological differeces, the preatal screeig uptake estimates from this data likage are lower tha those of screeig programs with madatory reportig of uptake ad results for moitorig purposes, such as i the Uited Kigdom. I the Uited Kigdom from 2007 to 2011, atioal uptake improved from 95% to 97% for rubella ad syphilis ad from 93% to 97% for HIV. 14 Youger wome udergoig preatal screeig are more likely to be tested for rubella, syphilis, ad HIV, while amog older wome there is more uptake of ati-hcv testig. For rubella, this may appropriately reflect the higher risk of rubella susceptibility amog youger wome. 15 I this study, the proportio of the liked preatal cohort whose results fell below the accepted threshold for rubella immuity (atibody levels 10 IU/mL) decreased from 6.7% to 5.0% betwee 2007 ad I Otario, overall rubella susceptibility amog preatal wome decreased from 4.9% to 4.2% betwee 2006 ad Syphilis ad HIV ew diagoses rates did ot have ay clear age treds, suggestig that emphasizig high screeig uptake across all ages is warrated. However, there are fewer older JUNE JOGC JUIN

7 Obstetrics wome udergoig preatal screeig; thus, the majority of ew diagoses of syphilis ad HIV are cotributed by wome aged 21 to 35 years. I BC, diagoses of syphilis at preatal screeig are geerally low but variable, with rates peakig i both the yougest ad oldest age groups; most cases are foud i 21- to 35-year-olds. British Columbia uses RPR testig oly, i cotrast to some other provices which use EIA as the primary test, allowig idetificatio of wome with a egative RPR but with a previous exposure. By usig RPR oly, we may uderestimate the past burde of syphilis i this populatio. From provicial reportable disease surveillace, cases of materal syphilis were idetified betwee 2007 ad 2011, with a decreasig aual tred. There were six cases of cogeital syphilis, with o cases i 2010 or I this data likage, we observed these low materal syphilis case umbers, although a dowward tred was ot detected over the study period. While BC is experiecig a period of low rates of materal ad cogeital syphilis, we kow that rates ca resurge over time There were o reports of cogeital syphilis i Alberta throughout the 1990s; the first case i a decade i Alberta was reported i 2002 after resurgece of locally acquired ifectious syphilis i persos reportig aoymous sex parterig. 17 I the same time frame, BC experieced a similar period of low rates of materal syphilis ad cogeital syphilis followed by a resurgece. 18 While reports of cases of syphilis i BC amog females, heterosexuals without other risk factors, street ivolved persos, ad female sex trade workers ad their patros have bee low ad decreasig i recet years, rates amog me who have sex with me have bee risig i BC sice the early 2000s. 19 Because of the potetial for trasmissio across groups ad for resurgece, uiversal preatal testig for syphilis remais vitally importat i detectig this treatable materal disease, so fetal ad eoatal ifectios ca be preveted. British Columbia ad Otario use the opt-i strategy for preatal HIV testig; a woma must coset to have a HIV test specifically, whereas uder the opt-out strategy HIV testig is icluded as oe of the routie preatal tests, ay of which a woma has the right to refuse. 8 I Otario, the proportio of pregacies tested for HIV was estimated at 96.2% i 2010, ad had icreased aually sice 1999 whe uiversal testig ad measures to improve uptake bega. 20 I this data likage, we estimated the proportio of BC wome udergoig preatal screeig that icluded HIV was 95.1% i 2010; this also was icreasig aually. However, we icluded all wome with a preatal code, but we do ot kow the umber of pregacies; a woma idetified i this way may be tested for other reasos such as fertility assessmet ad/or may ot go o to have a live birth. Preatal HIV test uptake i Otario was also foud to be lower at older ages. 8 I Alberta, a opt-out provice, 96.4% of preatal wome were tested for HIV i 2004 ad the HIV ifectio risk was three-fold higher amog the 3.6% who opted out tha amog those who opted i. 21 A importat public health idicator is the proportio of wome learig for the first time at preatal screeig that they are HIV positive. I a recet atioal review, Forbes et al. reported o the dramatic decreases i vertical HIV trasmissio i Caada i the era of highly active atiretroviral therapy; from 1997 to 2010, the trasmissio rate was estimated at 2.9% overall, 1% amog mothers receivig HAART, ad 0.4% if HAART was give for four weeks or more. 22 I 2011, the overall vertical trasmissio rate i Caada was estimated at 1.6%. 22 It is most desirable that wome are aware of their HIV status before presetig for preatal care. I geeral, we foud rates of ew diagoses of HIV to be low but variable across years ad age groups. I comparig the data likage to provicial surveillace of ew HIV diagoses i BC at preatal screeig, we fid very similar umbers ad low variable treds, with betwee 0 ad 3 cases diagosed per year sice ,12 The rate of ewly diagosed HIV ifectios i pregacy i Otario i 2010 was 13 cases per, compared to 6.5 cases per i BC amog preatally tested wome i the same year. I both provices, most cases were i wome uder 35 years, although some cases occurred i older wome. 20 The prevalece of HIV amog wome udergoig preatal screeig is a idicator of the populatio burde of disease i wome of childbearig age. I BC, HIV prevalece averaged 45.9 cases per per year over the five years of this study. We kow from provicial materal ifat cliical data that 30 kow HIV positive wome who had live births accessed specialized care i 2011, ad that o ifats had bee foud to have acquired HIV ifectio periatally i BC sice ,12 Although BC is experiecig a period of low aual umbers of ew HIV diagoses ad stable HIV prevalece i wome testig preatally, 505 periatally HIV-exposed ifats were reported i BC betwee 1984 ad 2011 (14.2% of all kow exposed ifats i Caada). 23 This highlights the eed to cotiue this importat screeig ad treatmet program. With the istitutio of STOP HIV-AIDS, a BC program to ehace screeig ad treatmet as prevetio, it would be expected that ew diagoses i pregacy would remai low as other meas of accessig testig are icreased JUNE JOGC JUIN 2014

8 Test Uptake ad Case Detectio of Syphilis, HIV, ad Hepatitis C Amog Wome Udergoig Preatal Screeig The rate of HCV test uptake at preatal screeig icreased 8.3% i the study period, while rates of ew diagoses decreased ad aual prevalece did ot chage. The decrease i ew diagosis rates may relate to a combiatio of kow ad possible treds: 1. HCV icidece is decreasig i the broader BC populatio, 2. opportuities for idetificatio of HCV outside pregacy may be improvig, ad 3. the icreased test uptake may be amog lower risk wome. Although more wome are beig tested o the basis of the same risk criteria each year, the severity of the risk caot be compared i these data, ad test uptake ca be iflueced by patiet ad/or provider awareess of risk-based testig ad iitiatives to expad testig based o other criteria (e.g., the recet recommedatios i the Uited States to icrease HCV screeig i baby boomers). 25 While the icidece of HCV is decreasig, 62.1 ewly idetified HCV cases per i 2011 i the preatal test populatio is high relative to the rates for syphilis ad HIV. BC s preatal HCV prevalece is also high relative to HIV prevalece, averagig cases per per year (0.6%) from 2007 to 2011, or cases per year. The fidig of Blasig et al. that BC s materal HCV prevalece i a aoymous serosurvey of all pregat wome was substatially higher tha from risk-based screeig 10 suggests that our prevalece estimate of 0.6% is a uderestimate. The BC rate is slightly higher tha the 0.5% seroprevalece foud i a uiversally screeed populatio of pregat wome i ier city Toroto betwee 2005 ad Usig the same risk factor criteria, ad i the cotext of decreasig HCV icidece i the broader populatio, chages i aual prevalece would ot be expected over the course of this study. Of the 260 kow HCV-positive wome idetified aually, we are uable to determie how may are aware of their diagosis ad have bee egaged ad retaied i care. I our study, 38.5% of wome with a prior positive ati-hcv test o record were re-tested at a subsequet preatal scree, suggestig that a proportio of wome ad/or their health care providers may have bee uaware of the previous diagosis. Kowledge of positive ati- HCV status durig ateatal care is eeded to trigger HCV-RNA testig to distiguish active from cleared ifectio ad to evaluate the risk of vertical trasmissio. Egagig ad retaiig HCV-ifected mothers i care ca decrease vertical trasmissio through modified obstetrical maagemet, ad ca prevet log-term adverse health outcomes i wome livig with hepatitis C as well as ifected ifats. Rates of HCV vertical trasmissio rage from 0% to 35%, with a average crude rate of 5.6%. 27 While all preatal screes do ot equate to a live birth, this suggests that 15 or more BC ifats per year may become chroically ifected ad require specialist follow-up. Although the total populatio of wome udergoig preatal screeig is geerally cosidered low risk for HCV, the primary risk factor of ijectio drug use (ever) is ofte uidetified durig preatal screeig. I a compariso of uiversal ad risk-based screeig i Toroto, either form of screeig was optimal for idetifyig cases. Testig positive for HCV was associated with elevated liver ezymes ad specific high severity risks: ijectig drugs (ever); itercourse with persos who iject drugs; or exposure to blood of a HCV-ifected idividual. 26 It is clear that idetifyig reproductive age wome who are potetially HCV positive presets opportuities to provide treatmet betwee pregacies ad to egage youg persos who are asymptomatic i HCV care before late complicatios. Recet advaces i HCV treatmet, icludig all-oral, iterfero-free regimes, ad improved cure rates, provide further opportuities for HCV positive wome. 28 This leds support to cosideratio of expaded or uiversal preatal screeig approaches for detectig HCV. CONCLUSION We have foud that despite a opt-i preatal testig strategy i BC, test uptake for commuicable diseases is high ad icreasig. Whether a opt-i or opt-out strategy is used, a key challege is esurig that pregat wome have access to comprehesive preatal care to maximize persoal ad ifat health outcomes. I the future, likage to provicial ateatal care records would allow us to better characterize screeig rates, icludig idetifyig pregacies ad/or live births ad the characteristics of wome who are ot beig screeed, to better iform screeig efforts. Uderstadig rates of HIV ifectio amog pregat wome oly would be more comparable to other provices, allowig atioal evaluatio of rates ad the potetial impact of the opt-i/ opt-out strategies. Cosiderig ways to more readily provide a woma s HCV testig history to providers of preatal screeig may reduce uecessary repeat testig of previously idetified ati-hcv positive cases ad may help the process of egagemet i further testig, cousellig, care ad, potetially, treatmet. Give the high prevalece of JUNE JOGC JUIN

9 Obstetrics positive ati-hcv tests foud i this preatal populatio, ad improvemets i HCV therapy, improvig HCV preatal screeig strategies ad egagemet of wome i care ad treatmet betwee pregacies are both eeded. ACKNOWLEDGEMENTS The authors wish to ackowledge the cotributios of Darrel Cook, Naveed Jajua, ad Amada Yu. REFERENCES 1. British Columbia Periatal Health Program. BCPHP obstetric guidelie 19, materity care pathway. Vacouver: BCPHP; 2010:1 24. Available at: BF43 496A-B113 5A50471B9C4B/0/ OBGuideliesMaterityCarePath19.pdf. Accessed March 7, British Columbia Miistry of Healthy Livig ad Sport. Core public health fuctios for BC: evidece review commuicable disease (secodary prevetio). Vacouver: British Columbia Miistry of Health; 2010:1 71. Available at: Commuicable_Disease_Secodary_Prevetio-Evidece_Review.pdf. 3. Boucher M, Grusli A; The Society of Obstetricias ad Gyaecologists of Caada Workig Group. The reproductive care of wome livig with hepatitis C ifectio. SOGC Cliical Practice Guidelie o. 96, October J Obstet Gyaecol Ca 2000;22(10): Available at: Accessed February 21, Gomez GB, Kamb ML, Newma LM, Mark J, Broutet N, Hawkes SJ. Utreated materal syphilis ad adverse outcomes of pregacy: a systematic review ad meta-aalysis. Bull World Health Orga 2013;90: Alberta Health ad Welless. Alberta preatal screeig program for selected commuicable diseases. Public Health Guidelies Available at: Screeig-Program-July-2007.pdf. 6. US Prevetive Services Task Force. Screeig for syphilis ifectio: recommedatios statemet. Rockville (MD): US Prevetive Services Task Force; Available at: summary/summary.aspx?ss=15&doc_id=5265&br= Patrick DM, Moey DM, Forbes J, Dobso SRM, Rekart ML, Cook DA, et al. Routie preatal screeig for HIV i a low-prevalece settig. CMAJ 1998;159: Wertheimer S. Wome ad HIV testig i Caada: barriers ad recommedatios as idetified by service providers: a summary of key research fidigs. Ottawa: Caadia AIDS Society; British Columbia Cetre for Disease Cotrol. British Columbia aual summary of reportable diseases Vacouver: BCCDC; Available at: F30377E3-D33E-4755-B3F4 6844E01BD678/0/FialAR2012.pdf. 10. Blasig A, Wager EC, Pi D, Bigham M, Remple VP, Craib KJ, et al.; the BC HCV Vertical Trasmissio Study Group. Hepatitis C ifectio amog pregat wome i British Columbia: reported prevalece ad critical appraisal of curret preatal screeig methods. Ca J Public Health 2011;102(2): British Columbia Cetre for Disease Cotrol. HIV i British Columbia: aual surveillace report Vacouver: BCCDC; Available at: British Columbia Cetre for Disease Cotrol. STI i British Columbia: aual surveillace report Vacouver: BCCDC; Available at: Micallef JM, Kaldor JM, Dore GJ. Spotaeous viral clearace followig acute hepatitis C ifectio: a systematic review of logitudial studies. J Viral Hepat 2006;13: Ateatal screeig for ifectious diseases i Eglad: summary report for Health protectio report. Lodo (GB): Health Protectio Report; 2012;6(36). Available at: hpr/archives/2012/ews3612.htm#as. 15. Lim GH, Harris T, Desai S, Crowcroft NS, Mazzulli T, Kozlowski T, et al. Rubella immuity amog preatal wome i Otario, BMC Ifect Dis 2013;13(362): Chakraborty R, Luck S. Maagig cogeital syphilis agai? The more thigs chage.... Curr Opi Ifect Dis 2007;20(3): Sigh AE, Sutherlad K, Lee B, Robiso JL, Wog T. Resurgece of early cogeital syphilis i Alberta. CMAJ 2007;177(1): Gilbert M, Kowles L, Neuma F, Ache M, Joes H, Ogilvie G, et al. Mother, ifat, ad syphilis: icreasig cause for cocer i British Columbia. BCMJ 2008;50(1):17, Hottes TS, Lidegger M, Cosolacio T, Wog S, Lester R, Motgomery C, et al. Ifectious syphilis amog gay, bisexual ad other me who have sex with me i British Columbia: 2003 to Vacouver: British Columbia Cetre for Disease Cotrol, Cliical Prevetio Services; Available at: rdolyres/b917a2f2 54C F80538CAC1E/0/CPS_ Report_Ifectious_Syphilis_MSMBC_ _ pdf. 20. Remis RS, Merid MF, Palmer RWH, Whittigham E, Kig SM, Daso NS, et al. High uptake of HIV testig i pregat wome i Otario, Caada. PLoS Oe 2012;7(11): Plitt S, Sigh A, Lee B, Preiksaitis JK. HIV Seroprevalece amog wome optig out of preatal HIV screeig i Alberta, Caada: Cli Ifec Dis 2007;45: Forbes JC, Alimeti AM, Siger J, Brophy JC, Bitum A, Samso LM, et al.; Caadia Pediatric AIDS Research Group (CPARG). A atioal review of vertical HIV trasmissio. AIDS 2012;26: Public Health Agecy of Caada. HIV ad AIDS i Caada: surveillace report to December 31, Ottawa: Surveillace ad Epidemiology Divisio, Cetre for Commuicable Diseases ad Ifectio Cotrol; British Columbia Miistry of Health. From hope to health: towards a AIDS-free geeratio. Victoria: BC Miistry of Health, Available at: from-hope-to-health-aids-free.pdf. 25. British Columbia Cetre for Disease Cotrol. (2012). British Columbia aual summary of reportable diseases Vacouver: BCCDC; Available at: F-BEC7 0C9316E57721/0/2011_CD_Aual_ Report_Fial.pdf. 26. McDermott CD, Moravac CC, Yudi MH. The effectiveess of screeig for hepatitis C i pregacy. J Obstet Gyaecol Ca 2010;32: Yeug LTF, Kig SM, Roberts EA. Mother-to-ifat trasmissio of hepatitis C virus. Hepatology 2001;34(2): Liag TJ, Ghay MG. Curret ad future therapies for hepatitis C virus ifectio. N Egl J Med 2013;368: JUNE JOGC JUIN 2014

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