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Objective: To evaluate cell‐free non‐invasive prenatal testing (cfNIPT) in pregnancies affected by mosaicism. Method: We assessed paired cfNIPT and chorionic villus sample (CVS) results from the same pregnancies in a case series of mosaicism detected in Central and North Denmark Regions from April 2014 to September 2018. Indications for the clinically obtained CVS, pregnancy markers and outcome were retrieved from The Danish Fetal Medicine Database. Results: Mosaicisms in CVS involved common aneuploidy, n = 14; sex chromosomal aneuploidies, n = 14; rare autosomal trisomies (RATs), n = 16 and copy number variants (CNVs) >5Mb, n = 9. Overall, 24/53 (45.3%; CI 95%: 31.8%–59.4%) of cases with mosaicism were detected by cfNIPT; highest for RATs (56%) and lowest for CNVs (22%). CfNIPT more commonly detected high‐level than low‐level mosaic cases (p = 0.000). CfNIPT detected 7/16 (43.8%; CI 95%: 21%–69%) clinically significant mosaic cases, either true fetal mosaicism or confined placental mosaicisms with adverse pregnancy outcome. There was a trend toward a higher risk for adverse outcome in pregnancies where mosaicism was detected by cfNIPT compared to pregnancies where mosaicism was not detected by cfNIPT (p = 0.31). Conclusion: CfNIPT has a low detection rate of mosaicism, including pregnancies with clinically significant mosaicism. However, abnormal cfNIPT results may be a predictor of adverse pregnancy outcomes. Key points: What´s already known about this topic? The prevalence of mosaicism in chorionic villus samples is 2%–4%Fetoplacental mosaicism is one of the causes behind false results with cell‐free non‐invasive prenatal testing (cfNIPT) What does this study add? CfNIPT detects ∼50% of mosaic cases revealed in chorionic villus samplesThe detection rate of mosaicism by cfNIPT correlates with the level of mosaicism in chorionic villus samplesIn case of placental mosaicism, a positive cfNIPT result may be a predictor of adverse pregnancy outcome [ABSTRACT FROM AUTHOR]

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by the absence or underdevelopment of the uterus and upper part of the vagina. It is usually diagnosed during adolescence, and the present study investigates how women experience and negotiate to live with MRKH syndrome long-term. From January to March 2021, eighteen Danish women with MRKH syndrome participated in semi-structured interviews via video conference. The mean time since diagnosis was 11.5 years. A thematic analysis using the life course framework as a theoretical approach was applied. The analysis identified the diagnosis as a turning point, that dramatically altered the women's imagined futures. Not conforming to dominant social norms regarding sexuality and pregnancy meant that the women continuously managed and negotiated the meaning and impact of MRKH syndrome in relation to the five principles of the life course perspective: (1) Lifelong development, (2) Timing, (3) Human agency, (4) Linked lives, and (5) Historical time and place. Using the life course framework contributed to a holistic understanding of life with MRKH syndrome by showing how the meaning and consequences of the congenital condition changed over time and in adaptation to gendered and age-related social norms and expectations. The perceived meaning and impact of living with Mayer-Rokitansky-Küster-Hauser syndrome change over time, and women's information and support needs thus change accordingly Sensitive, clinical communication is essential when discussing treatment options Online communities may provide support and reduce feelings of loneliness [ABSTRACT FROM AUTHOR]

Introduction: In this register‐based study of pregnancies in Denmark, we assessed the associations between maternal age and the risk of fetal aneuploidies (trisomy 21, trisomy 18, trisomy 13, triploidy, monosomy X and other sex chromosome aberrations). Additionally, we aimed to disentangle the maternal age‐related effect on fetal aneuploidies by cases with translocation trisomies and mosaicisms. Material and methods: We followed a nationwide cohort of 542 375 singleton‐pregnant women attending first trimester screening in Denmark between 2008 and 2017 until delivery, miscarriage or termination of pregnancy. We used six maternal age categories and retrieved information on genetically confirmed aneuploidies of the fetus and infant from the national cytogenetic register. Results: We confirmed the known associations between advanced maternal age and higher risk of trisomy 21, 18, 13 and other sex chromosome aberrations, especially in women aged ≥35 years, whereas we found no age‐related associations with triploidy or monosomy X. Cases with translocation trisomies and mosaicisms did not influence the overall reported association between maternal age and aneuploidies. Conclusion: This study provides insight into the accurate risk of fetal aneuploidies that pregnant women of advanced ages encounter. [ABSTRACT FROM AUTHOR]

Objective: To investigate if the Down syndrome phenotype differs according to the result of first‐trimester combined screening (FTS). Method: We included all Down syndrome cases diagnosed by karyotype in pregnancy or after birth in Denmark during 2005–2018. We compared screen positive (odds ≥1:300) and screen negative (odds <1:300) cases as well as screen result subgroups with respect to anthropometrics, congenital malformations, childhood diseases, and hospitalization. Results: Absolute measures of fetal and birth anthropometrics were comparable between groups. A prenatal malformation diagnosis was more prevalent among screen positive than screen negative cases. Analyses suggested that this could reflect a detection bias. Cases with a screen result of 1:2–1:10 had a higher probability of being diagnosed with a malformation prenatally and with severe congenital heart disease (CHD) postnatally compared with a result of 1:11–1:300. Screen positive cases more often had non‐severe CHD but less often a non‐heart malformation compared with screen negative cases, while proportions of severe CHD were similar in these groups. Data on hospitalizations showed inconsistent results. Conclusion: The 1:300 screening threshold had limited or no value in predicting Down syndrome phenotype severity. In contrast, cases with a screen result between 1:2 and 1:10 may represent a more severe phenotype. Key points: What's already known about this topic? The severity of the Down syndrome phenotype is variable and unpredictable.The first‐trimester combined screening (FTS) is based on measures, such as nuchal translucency, known to be associated with adverse outcomes, suggesting predictive potential. What does this study add? The severity of the Down syndrome phenotype did not consistently differ between screen positive (odds at FTS ≥1:300) and screen negative (odds at FTS <1:300) cases.Screen positive Down syndrome cases with odds 1:2–1:10 may, however, be at risk of a severe phenotype.In screen negative Down syndrome cases, the sensitivity of a prenatal diagnosis of congenital malformations may be lower than that among screen positive Down syndrome cases. [ABSTRACT FROM AUTHOR]

Objectives: Cystic fibrosis (CF) is one of the most common severe autosomal recessive disorders. Prenatal or preconception CF screening is offered in some countries. A maternal blood sample in early pregnancy can provide circulating trophoblasts and offers a DNA source for genetic analysis of both the mother and the fetus. This study aimed to develop a cell‐based noninvasive prenatal test (NIPT) to screen for the 50 most common CF variants. Methods: Blood samples were collected from 30 pregnancies undergoing invasive diagnostics and circulating trophoblasts were harvested in 27. Cystic fibrosis testing was conducted using two different methods: by fragment length analysis and by our newly developed NGS‐based CF analysis. Results: In all 27 cases, cell‐based NIPT provided a result using both methods in agreement with the invasive test result. Conclusion: This study shows that cell‐based NIPT for CF screening provides a reliable result without the need for partner‐ and proband samples. Key points: What's already known about this topic?Many pregnant women are positive towards prenatal screening for Cystic fibrosis (CF).The only current pregnancy marker is echogenic bowel in the second trimester, but this test has low sensitivity and specificity. What does this study add?Prenatal screening for CF can be done using circulating trophoblasts isolated from maternal blood early in pregnancyCirculating trophoblasts can provide screening for CF as a simple single‐visit setup without the need for a paternal sample. [ABSTRACT FROM AUTHOR]