Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing:Follow-up results of the TRIDENT-2 study

In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2 study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weigh

The misuse of ANCOVA in neuroimaging studies

Analysis of Covariance (ANCOVA) is a technique that is frequently used in neuroimaging studies to control for covariates. An assumption of ANCOVA is that the between-subjects factor and the covariate are independent. In some observational studies in the neuroimaging literature, this assumption is violated. The question that these studies attempt to answer is what the difference would be between group means on the dependent variable if the group means on the covariate were equal. However, when there is a dependency between the between-subjects factor and the covariate, then correcting for differences between groups on the covariate may misrepresent the factor and distort its definition. Moreover, the situation where all subjects have equal scores on the covariate may be unrealistic. If the assumption of independence is violated, there are several procedures to follow. Generally, it is of crucial importance to consider the question what it means to correct for a variable that has a relationship with the factor under study. In case of an observational study, ANCOVA does not facilitate the estimation of the causal effect of the between-subjects factor. When two variables are related, there is no statistical method available to correct for this relationship

The misuse of ANCOVA in neuroimaging studies

Analysis of Covariance (ANCOVA) is a technique that is frequently used in neuroimaging studies to control for covariates. An assumption of ANCOVA is that the between-subjects factor and the covariate are independent. In some observational studies in the neuroimaging literature, this assumption is violated. The question that these studies attempt to answer is what the difference would be between group means on the dependent variable if the group means on the covariate were equal. However, when there is a dependency between the between-subjects factor and the covariate, then correcting for differences between groups on the covariate may misrepresent the factor and distort its definition. Moreover, the situation where all subjects have equal scores on the covariate may be unrealistic. If the assumption of independence is violated, there are several procedures to follow. Generally, it is of crucial importance to consider the question what it means to correct for a variable that has a relationship with the factor under study. In case of an observational study, ANCOVA does not facilitate the estimation of the causal effect of the between-subjects factor. When two variables are related, there is no statistical method available to correct for this relationship

The Dimensional Assessment of Personality Pathology – Short Form for Adolescents (DAPP-SF-A): normative data for Flemish adolescents aged 16 to 21 years

Background:The Dimensional Assessment of Personality Pathology – Short Form for Adolescents (DAPP-SF-A) is an age-adapted version of the DAPP Basic Questionnaire (DAPP-BQ). The psychometric properties of this questionnaire were established by Tromp and Koot. However, norming data are currently available exclusively for Dutch adolescents.Objective:The main aim of this study was to provide community-based norming data for the DAPP-SF-A in Flemish adolescents and separately for boys and girls. The second aim was to compare the Flemish norms with the Dutch norms.Method:The sample consisted of 425 adolescents (52% girls), aged 16 to 21 years (mean, 18.6; SD, 1.16), from the general Flemish population. In 2012, all respondents completed the DAPP-SF-A and the Youth Self-Report as a part of the longitudinal Flemish Study on Parenting, Personality, and Development.Results:Internal consistency reliabilities of the lower-order dimensions were acceptable to good (a ranged from 0.71 to 0.87, median=0.85, mean item-rest correlations ranged from 0.44 to 0.67). The lower-order dimensions showed distinctive mean patterns for boys and girls, with higher scores for girls on Affective Instability and Insecure Attachment [effect sizes (d) were both −0.35] and higher scores for boys on all lower-order dimensions of Dissocial Behavior, Inhibitedness, and three lower-order dimensions of Emotional Dysregulation (d ranged from 0.21 to 0.79). The comparison of the Flemish scores with the Dutch scores showed substantial inter-cultural differences (d ranged from 0.13 to −1.78).Conclusions:The DAPP-SF-A shows satisfactory reliability in a Flemish community-based sample of adolescents. Furthermore, given the differences between boys and girls, the use of gender-based norms seems appropriate. Finally, substantial differences with the Dutch general population norms warrant the use of separate norms in Flemish adolescents

The Multidimensional Wellbeing in Youth Scale (MWYS): Development and Psychometric Properties

In the present multi-sample mixed method study, we developed a novel assessment tool of youth wellbeing, the Multidimensional Wellbeing in Youth Scale (MWYS). In Study 1, an online survey study among Dutch-speaking adolescents and young adults (N = 339, Mage = 18.44 years, SD = 3.53, 79 % females) was conducted to inspect which initial MWYS-items were viewed as being important for their wellbeing. In Study 2, we co-evaluated the original MWYS-items and co-created new items with adolescents and young adults (N = 25) via focus groups. In Study 3, we examined the validity and reliability of the updated MWYS in a new sample of Dutch-speaking adolescents and young adults (N = 239, Mage = 19.68 years, SD = 4.40, 68 % females). Principal Components Analyses revealed five preliminary components of adolescent wellbeing: 1) having impact, purpose, and meaning; 2) dealing with stress and worry; 3) family relationships; 4) self-confidence; and 5) feeling respected, appreciated, and loved. These MWYS-components were related to other measures of mental health and wellbeing, and the MWYS showed good internal consistency and test-retest reliability. In conclusion, the MWYS was found to be a valid and reliable measure of youth wellbeing

Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study

In the TRIDENT-2 study, all pregnant women in the Netherlands are offered genome-wide non-invasive prenatal testing (GW-NIPT) with a choice of receiving either full screening or screening solely for common trisomies. Previous data showed that GW-NIPT can reliably detect common trisomies in the general obstetric population and that this test can also detect other chromosomal abnormalities (additional findings). However, evidence regarding the clinical impact of screening for additional findings is lacking. Therefore, we present follow-up results of the TRIDENT-2 study to determine this clinical impact based on the laboratory and perinatal outcomes of cases with additional findings. Between April 2017 and April 2019, additional findings were detected in 402/110,739 pregnancies (0.36%). For 358 cases, the origin was proven to be either fetal (n = 79; 22.1%), (assumed) confined placental mosaicism (CPM) (n = 189; 52.8%), or maternal (n = 90; 25.1%). For the remaining 44 (10.9%), the origin of the aberration could not be determined. Most fetal chromosomal aberrations were pathogenic and associated with severe clinical phenotypes (61/79; 77.2%). For CPM cases, occurrence of pre-eclampsia (8.5% [16/189] vs 0.5% [754/159,924]; RR 18.5), and birth weight <2.3rd percentile (13.6% [24/177] vs 2.5% [3,892/155,491]; RR 5.5) were significantly increased compared to the general obstetric population. Of the 90 maternal findings, 12 (13.3%) were malignancies and 32 (35.6%) (mosaic) pathogenic copy number variants, mostly associated with mild or no clinical phenotypes. Data from this large cohort study provide crucial information for deciding if and how to implement GW-NIPT in screening programs. Additionally, these data can inform the challenging interpretation, counseling, and follow-up of additional findings