What CARs can tell us about screening programmes & their population effects: a model for trisomy 21

Ann M Tonks (WMCAR PHE), Adam S Gornall (The Shrewsbury & Telford Hospital NHS Trust)

Background• Congenital anomaly surveillance & screening are both population-based

public health activities

• CARs collect affected cases from the total/target population;including the screened and unscreened cohorts

• Screening detection rates (DTRs) are needed to• provide women with information to make informed choices

• monitor performance

• Modelled DTRs for T21 screening tests are available from DQASS for service-based (laboratory) cohorts only

• There is a paucity of data on the total population effects and performance of screening programmes

2 WMCAR T21 BINOCAR 2014

Methods - CARsT21 cases were identified from a regional BINOCAR register (WMCAR)

Population-based data using multiple sources and active case-finding

Systems that do not actively collect all postnatally identified cases (unscreened and screen –ve cases) will:

UNDER-estimate prevalenceOVER-estimate detection rates

Reliable methodology, generates good quality data and ensures highest possible ascertainment†

† Savva G M, Morris J K. Ascertainment and accuracy of Down syndrome cases reported in congenital anomaly registers in England and Wales. Arch Dis Child Fetal Neonatal Ed 2009; 94: F23–F27.

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Methods – T21 WMCARSetting

West Midlands: annual birth population of ≈ 73,500, 15 Acute Trusts

T21 screening – combined or quad screening (Jan 2011+)

Case definition

All cytogenetically confirmed T21 cases: screened (NHS & private) & unscreened

Selected by EDD (Jul 2011-Jun 2013) & postcode at delivery

All outcomes miscarriages, TOPs (all gestations), & registerable births

Affected population, excludes screen +ve cases where karyotyping normal/declined

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Methods – T21 data collection/validationProspective reporting of cases by Trusts (via Local LCO) or other sources

Diagnoses/ascertainment validated with cytogenetics labs (regional & private), NDSCR annual, surrounding CARs

Retrospective validation of cases by Trusts (LCOs):

a) correctly allocated to Trust at booking

b) details of the screening offer/results collected

Screened: screening data are confirmed with biochemistry labs

Unscreened: choices confirmed in maternal notes or dating USS

confirm eligibility – late bookers or IUD at dating

Provisional Trust lists of T21 cases are sent to LCOs for cleaning

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Results - CARs397 cases of T21 (2 years)

Total prevalence 25.9 / 10,000 births (95%CI 24.2-29.5)

Median mat age at EDD (36, IQR 31-40); background (all births) 28 years

Live births, n=202 (50.9%)

Live birth prevalence 13.1 / 10,000 live births (95%CI 11.3-14.9)

Mortality: stillbirths and infant deaths, n= 28

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Combined(81.5%)

DTR 72.4% (65.9-78.9)MOBP 90%/2%

Quad DTR 63.4% (48.7-78.2)MOBP 75%/3%

NHSSCREENED

n=222

screen -ven=65

Screen DTR70.7% (64.7-76.7)

75.1%

DIAGNOSESNHS screening

n=118

screen +ven=157

PND 56.3% (49.8-62.8)

ELIGIBLEn=377

Coverage 58.9%

privatescreenn=20

UNSCREENEDn=155

INELIGIBLEn=20

diagnostictest (other)

n=5

declinedscreenn=88

missed screen

n=4

abnormaldating scan

n=38

T21 AFFECTED CASESTOTAL POPULATION

n=397

5.0%

DIAGNOSISother indication

n=72

ALL PRENATAL DIAGNOSES

n=190

Population PND 47.9% (42.9-52.8)

PND 37.1% (30.-44.3)

Uptake of TOP = 85.8%, n=163

Results: combined screening DTR

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2011-12 2012-130%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%MOBP

Results: maternal ethnic group

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White British Other

Total affected T21 292 105

Median mat age EDD (IQR) yrs 37(31-40)

36(31-39)

Screening uptake in eligible, p<0.01 63.0%(57.3-68.6)

46.9% (36.9-56.9)

NHS screen DTR, p=0.05 74.0%(67.6-80.5)

57.8%(43.3-72.2)

Uptake PND in screen +ve 77.9% 61.5%

Population PND rate, p<0.01 54.8%(49.1-60.5)

28.6%(19.9-37.2)

Uptake TOP following PND 85.0%(79.5-90.5)

90.0%(79.3-100)

Results: CAR outcomes (total)

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Prevalence: total & live birth, long term trends

Pregnancy outcomes, mortality rates, long term survival

Link to exposures (fluoridation)

Population PND rates

timing of prenatal diagnosis

methods of invasive testing

Workload/work force planning

Results: screening tests & programme

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Population-based (e.g. Area Team) or service-based (e.g. booked at Trust)

Screened cohort:

Which type of test? %combined v %quad

Test performance (DTR) – observed not modelled

Pathway activity – uptake of PND, uptake of TOP

Screening Programme:

Eligible population size

Offer coverage/screening uptake (affected group only)

Missed screen (eligible cases screening not offered/completed)

Results: stakeholders

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Trusts:

Case list for Annual Antenatal & Newborn Screening Audit Submission

Missed screen

SSS screen –ve (combined) image review

Summary report for Trust Screening Board

Area Team:

Screening outcomes

Screening lab:

Own DTR

Audit and review of screen –ve cases

Conclusions• CARs provide a picture of screening performance and its population effects

in affected cases

• Quantify the benefits of screening, but not the risks.

• CARs can generate reliable service and population-based screening outcomes for an entire programme or a specific test within it.

• There is an opportunity to use routinely-collected CAR data to inform other antenatal screening programmes.

West Midlands

• Combined screening DTR did not achieve the NSC MOBP.

• Population prenatal diagnosis rates varied by maternal ethnic group.

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AcknowledgementsAll clinical, laboratory, and administrative staff who notify WMCAR, especially Local Screening Co-ordinators

WMCAR staff for processing, coding, completing notifications

14 WMCAR T21 BINOCAR 2014

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Trisomy 21 prenatal diagnosis (karyotype)

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1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 20120%

10%

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50%

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TRISOMY 21 PRENATAL DIAGNOSIS

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17 WMCAR & T21 CKO visit

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T21 prenatal diagnosis timing

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1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011

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Maternal age rate Screen +ve rate

Headings are set in 40 pt ArialLarge body copy should be set in 18pt Roman

Large subheadings set in 18pt Arial

Text

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Notifications from Trusts

Data cleaningascertainment

Data cleaningScreening

Regional Cytogenetics

National Down’s Register

HES data

Biochemistry labsx 2

Provisional Trust listLCO cleans

DATA COMPLETE

Final Trust listLCO

Screened casesBiochemistry lab

Final Trust reportHOM – new 2012

No specimen found

Baby alive at 1st USS

Gestation at1st ultrasound scan

Check biochemistry lab for specimens

Confirm as affected pregnancy

Ineligible for screeningIUD

ScreenedPregnancy

Case confirmed asELIGIBLE

Review Green PHR page 7Screening Tests for Downs syndrome

Review tick boxes“Screening offered”

Review tick boxes“Accepted by mother”

SCREENINGDECLINED

20+0 weeks or lessCRL <= 84 mm OR HC < 173 mm

YES

NO

Mother acceptedTicked as “No”

Screening offeredNot ticked

Screening offeredTicked as “Yes”

Screening offeredTicked as “No”

Mother acceptedTicked as “Yes”

Mother acceptedNot ticked

Specimenfound

20+1 weeksor more

SCREENING NOT OFFERED

SCREENING ACCEPTED & NOT DONE

SCREENING OFFER NOT DOCUMENTED

SCREENING ACCEPTANCE NOT

DOCUMENTED

Correctpregnancy

Ineligible for screeningLATE BOOKER

Gestation atbooking appt

Case confirmed asUNSCREENED

20+1 weeksor more

HC 173+ mm

20+0 weeksor less

REVIEW DELAYS IN USS APPTS FOR URGENT

CASES

Specimen from previous/subsequent

pregnancy

SUSPECTEDMISSED CASE

SURUSS & Private vs NHS

Biochemistry

NT measurement

Risk calculation

All sizes

Low riskHigh risk

TR, DV

Biochemistry

NT measurement

Risk calculation

Low riskHigh risk

< 3.5 mm>= 3.5 mm

Large NTpathway