Malone 2005.
| Clinical features and settings | Routine screening | |
| Participants | 38,033 participants USA ‐ multi‐centre study (15 centres) October 1999 to December 2002 Pregnant women 21.6% of women aged ≥ 35 years Singleton pregnancies Live fetuses 10‐13 and 15‐18 weeks' gestation |
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| Study design | Prospective cohort | |
| Target condition and reference standard(s) | Down’s syndrome: 92 cases (87 had first trimester and second trimester screening) Reference standards: amniocentesis (offered to women with positive results from any screening test) or follow‐up to birth |
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| Index and comparator tests | Maternal age First trimester NT in 36,306 patients (92.9%) First trimester PAPP‐A and free ßhCG in 37,843 patients (99.5%) Second trimester AFP, total hGC, uE3 and inhibin‐A in 35,236 patients (92.6%) All tests done in 33,546 patients (88.2%) |
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| Follow‐up | Follow‐up with computerised tracking system. Medical records were reviewed in cases of 1) possible medical problem suspected 2) positive screening test results with no karyotype data, 3) 10% random sample of all enrolled patients. Follow‐up to birth complete in 36, 378 patients (97%) | |
| Aim of study | To evaluate first trimester and/or second trimester screening tools for Down's syndrome | |
| Test characteristics | ||
| Reference standard used | ||
| Notes | Unclear which types of patients did not have follow‐up data. Appears that aborted/miscarried fetuses did not have follow‐up (note in table) | |
| 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 | No | Not all women received a reference standard (3% had no ascertainment of pregnancy outcome, patients not excluded from 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 | NT failed or rejected at review in 7.1% or women |
| Withdrawals explained? All tests | Yes | Details given for patients who did not undergo different index tests |