Effectiveness of 12-13-week scan for early diagnosis of fetal congenital anomalies in the cell-free DNA era.

OBJECTIVES: The main aim of this study was to assess the proportion and type of congenital anomalies, both structural and chromosomal, that can be detected at an early scan performed at 12-13 weeks' gestation, compared with at the 20-week structural anomaly scan offered under the present screening policy. Secondary aims were to evaluate the incidence of false-positive findings and ultrasound markers at both scans, and parental choice regarding termination of pregnancy (TOP). METHODS: Sonographers accredited for nuchal translucency (NT) measurement were asked to participate in the study after undergoing additional training to improve their skills in late first-trimester fetal anatomy examination. The early scans were performed according to a structured protocol, in six ultrasound practices and two referral centers in the north-east of The Netherlands. All women opting for the combined test (CT) or with an increased a-priori risk of fetal anomalies were offered a scan at 12-13 weeks' gestation (study group). All women with a continuing pregnancy were offered, as part of the 'usual care', a 20-week anomaly scan. RESULTS: The study group consisted of 5237 women opting for the CT and 297 women with an increased a-priori risk of anomalies (total, 5534). In total, 51 structural and 34 chromosomal anomalies were detected prenatally in the study population, and 18 additional structural anomalies were detected after birth. Overall, 54/85 (63.5%) anomalies were detected at the early scan (23/51 (45.1%) structural and all chromosomal anomalies presenting with either an increased risk at first-trimester screening or structural anomalies (31/34)). All particularly severe anomalies were detected at the early scan (all cases of neural tube defect, omphalocele, megacystis, and multiple severe congenital and severe skeletal anomalies). NT was increased in 12/23 (52.2%) cases of structural anomaly detected at the early scan. Of the 12 cases of heart defects, four (33.3%) were detected at the early scan, five (41.7%) at the 20-week scan and three (25.0%) after birth. False-positive diagnoses at the early scan and at the 20-week scan occurred in 0.1% and 0.6% of cases, respectively, whereas ultrasound markers were detected in 1.4% and 3.0% of cases, respectively. After first- or second-trimester diagnosis of an anomaly, parents elected TOP in 83.3% and 25.8% of cases, respectively. CONCLUSIONS: An early scan performed at 12-13 weeks' gestation by a competent sonographer can detect about half of the prenatally detectable structural anomalies and 100% of those expected to be detected at this stage. Particularly severe anomalies, often causing parents to choose TOP, are amenable to early diagnosis. The early scan is an essential part of modern pregnancy care. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Approximate entropy studies of hormone pulsatility from plasma concentration time series: influence of the kinetics assessed by simulation.

Approximate entropy (ApEn) is a method developed in the early nineties to quantify the "regularity" of a time series. In recent years, it has been vigorously employed to study the oscillatory/pulsatile secretory behavior of many hormones and found capable of successfully identifying pathological or prepathological states characterized by an enhanced secretion irregularity. Since hormone secretion rate is nonaccessible to direct measurement, ApEn is usually calculated from the time series of the hormone concentrations in plasma. However, the plasma concentration time course also reflects the whole-body kinetics of the hormone and can thus only provide a distorted portrait of the secretion rate at the gland level. In this paper, we investigate by simulation whether and how this distortion can influence the study of the regularity of hormone pulsatility by ApEn. Pulsatile secretion time series with different degrees of irregularity are simulated by varying the statistics of the random parameters which describe the secretory pulses. Then, plasma concentration time series are obtained by convolution with the hormone impulse response. Different degrees of impulse response smoothness are also considered in order to vary the amount of the distortion introduced. Results show that ApEn computed from secretion time series consistently discriminated better than ApEn calculated from plasma concentration time series among processes with different degrees of regularity. In addition, smoother impulse responses decreased the ApEn differences between plasma concentration time series corresponding to different degrees of secretion regularity. Therefore, the power of the ApEn index in the study of hormone pulsatility can potentially be enhanced by applying it to the hormone secretion time series.