The added value of CPR and uterine Doppler at 33 weeks of gestation for detecting defective growth is poor.

Objective To assess the added value of chromosomal microarray analysis (CMA) over conventional karyotyping to assess the genetic causes in stillbirth. Methods To identify relevant studies, published in English or Spanish and without publication time restrictions, we performed a systematic search of PubMed, SCOPUS and ISI Web of Science databases, The Cochrane Library and the PROSPERO register of systematic reviews, for case series of fetal loss ≥ 20 weeks of gestation, with normal or suspected normal karyotype, undergoing CMA and with at least five subjects analyzed. To investigate quality, two reviewers evaluated independently the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool. For the meta‐analysis, the incremental yield of CMA over karyotyping was assessed by single‐proportion analysis using a random‐effects model (weighting by inverse variance). We assessed heterogeneity between studies and performed a sensitivity analysis and a subgroup analysis of structurally abnormal (malformed or growth‐restricted) and normal fetuses. Results Included in the meta‐analysis were seven studies involving 903 stillborn fetuses which had normal karyotype. The test success rate achieved by conventional cytogenetic analysis was 75%, while that for CMA was 90%. The incremental yield of CMA over conventional karyotyping based on the random‐effects model was 4% (95% CI, 3–5%) for pathogenic copy‐number variants (pCNVs) and 8% (95% CI, 4–17%) for variants of unknown significance. Subgroup analysis showed a 6% (95% CI, 4–10%) incremental yield of CMA for pCNVs in structurally abnormal fetuses and 3% (95% CI, 1–5%) incremental yield for those in structurally normal fetuses. The pCNV found most commonly was del22q11.21. Conclusions CMA, incorporated into the stillbirth work‐up, improves both the test success rate and the detection of genetic anomalies compared with conventional karyotyping. To achieve a genetic diagnosis in stillbirth is particularly relevant for the purpose of counseling regarding future pregnancies. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.