Clinical experience across the fetal-fraction spectrum of a non-invasive prenatal screening approach with low test-failure rate.

OBJECTIVE: To describe our clinical experience across the entire range of fetal-fraction (FF) measurements of a non-invasive prenatal screen (NIPS) that uses whole- genome sequencing (WGS). METHODS: We analyzed retrospectively results from 58 105 singleton pregnancies that underwent NIPS on a customized WGS platform during an 8-month period and assessed clinical test performance for trisomy 21, trisomy 18 and trisomy 13. Pregnancy outcomes were sought for all screen-positive patients and for 18% of screen-negative patients. As differences in outcome-collection response rates could artificially impact test-performance calculations, we computed inferred sensitivity, specificity, positive predictive values (PPV) and negative predictive values adjusted for ascertainment bias. RESULTS: The screening test yielded a result for 99.9% (n = 58 048) of patients, meaning that approximately 1 in 1000 patients received a test failure (i.e. test failure rate = 0.1%). Of pregnancies with a test result, 572 (1%) screened positive for one of the common aneuploidies (362 for trisomy 21, 142 for trisomy 18 and 68 for trisomy 13). Informative outcomes were received for 237 (41.4%) patients with a screen-positive result and 3258 (5.7%) of those with a screen-negative result. In the full cohort, inferred sensitivities for trisomy 21, trisomy 18 and trisomy 13 were 99.7%, 96.8% and 94.3%, respectively, and PPVs were 93.1%, 85.2% and 48.4%, respectively. If a FF threshold of 4% had been employed to guard against false negatives, calculated sensitivities for the three aneuploidies would not have changed significantly, yet, importantly, the overall test-failure rate would have increased to 6.6% (n = 3829), impacting 1 in 15 women. CONCLUSIONS: Our clinical experience demonstrates that a customized WGS-based NIPS without a FF threshold achieves high accuracy while maintaining a low test-failure rate of 0.1%. As such, alternative strategies to ensure high accuracy of detection of common aneuploidies in samples with low FF (such as redraw after test failure, redrawing at a later gestational age, risk scoring based on FF) are not necessary for this screening approach. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Suspected macrosomia? Better not tell.

OBJECTIVE: To evaluate the management policy of delivery in a suspected macrosomic fetus and to describe the outcome of this policy. STUDY DESIGN: For this prospective observational study we followed the management by reviewing the medical records of 145 women and their infants. The study population included women at term admitted to the obstetrics department with suspected macrosomic infants, as was diagnosed by an obstetrician and/or by fetal sonographic weight estimation of > or =4,000 g. The comparison group (n = 5,943) consisted of all women who gave birth during the data collection period. RESULTS: Induction of labor and cesarean delivery rates in the macrosomic pregnancies (actual birth weight >4,000 g) of the study group were significantly higher when compared with the macrosomic pregnancies of the comparison group. When comparing the non-macrosomic to the macrosomic pregnancies (actual birth weight 4,000 g) of the study group no significant difference was demonstrated regarding maternal or infant complications. The sensitivity, specificity and positive predictive value of the methods used for detecting macrosomia were 21.6, 98.6 and 43.5%, respectively. CONCLUSION: Our ability to predict macrosomia is poor. Our management policy of suspected macrosomic pregnancies raises induction of labor and cesarean delivery rates without improving maternal or fetal outcome.