Wald 2003b.
| Clinical features and settings | Routine screening | |
| Participants | 606 participants: 101 cases, 505 controls matched for gestation, duration of storage and centre UK and Austria ‐ multi‐centre trial September 1996 to April 2000 Pregnant women 9‐13 and 14‐20 weeks' gestation |
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| Study design | Case‐control study | |
| Target condition and reference standard(s) | Down's syndrome: 101 cases Rerence standards: invasive testing (following second trimester screening) or follow‐up to birth |
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| Index and comparator tests | First trimester NT (midsagittal section, optimal magnification of thickness of translucent space between inner skin surface and fascia covering cervical spine (white black interface (outer) ‐ black white interface (inner), 41 models of ultrasound machine, 20 minutes allotted scanning time) First trimester and second trimester serum AFP, hCG, UE3, PAPPA, free ßhCG (time resolved fluoroimmunoassay, AutoDELFIA) First trimester and second trimester inhibin A (Sandwich enzyme linked immunosorbent assay, Oxford Bioinnovation) First trimester and second trimester urinary beta core fragment, total‐hCG, ITA and free ßhCG (ITA and beta core fragment, Quest diagnostics USA) |
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| Follow‐up | Follow‐up by: 1) Staff at local hospitals completed a study outcome form at, or just after. delivery, 2) Study records of CVS, amniocentesis or karyotype at birth linked to information from cytogenic laboratories, 3) Study records linked to records of cases of Down's syndrome from the National Down's Syndrome Cytogenetic Register, 4) Information obtained from local obstetrical outcome records, 5) Forms sent to all women with a request to return details of the outcome of their pregnancy, 6) Individual searches in respect of women whose outcomes of pregnancy had not been obtained by any of the previous methods. 96% Birth/Karyotype full outcome documentation obtained | |
| Aim of study | To identify the most effective, safe and cost effective strategy for antenatal screening for Down's syndrome using NT, maternal serum and urine markers in the first and second trimesters of pregnancy and maternal age in various combinations | |
| Test characteristics | ||
| Reference standard used | ||
| Notes | Performance of screening assessed at 17 weeks' gestation. Study tried to be non‐interventional in the first trimester ‐ second trimester testing was aimed to be used as the basis for any referral for invasive testing | |
| Table of Methodological Quality | ||
| Item | Authors' judgement | Description |
| Representative spectrum? All tests | Yes | Routine screening of typical pregnant population |
| Acceptable reference standard? All tests | Yes | Karyotyping or follow‐up to birth |
| Partial verification avoided? All tests | Unclear | 4% of total patient cohort did not have a documented outcome of pregnancy. Unclear if any of these included in nested case‐control study |
| Differential verification avoided? All tests | No | Choice of reference standard depended on index test results |
| Incorporation avoided? All tests | Yes | Reference standard was independent of the index test |
| Reference standard results blinded? All tests | No | Reference standard interpreted with knowledge of index test results |
| Index test results blinded? All tests | Yes | Index test interpreted without knowledge of reference standard results |
| Relevant clinical information? All tests | Yes | Information available as would be in standard clinical practice |
| Uninterpretable results reported? All tests | Yes | Rates of NT failure on average 9%. Pre‐10 weeks' gestation, > 33% failure rate, declined to 7% at 12 weeks |
| Withdrawals explained? All tests | No | No details of withdrawals given |