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In two cases, cell-based noninvasive prenatal testing (cb-NIPT) detected copy number variations (CNVs): a 7 Mb deletion of 15q11q13 covering the Prader-Willi region and a 4.6 Mb deletion at 3p26.3p26.1. This may potentially be an improved noninvasive alternative for the detection of smaller CNVs. Denmark has a tax-financed combined first trimester screening program that consists of a nuchal translucency scan, maternal age, fβ-hCG, and PAPP-A measurements. The program has an uptake of above 93%. 1,2 If a woman has a risk equal to or greater than 1:300 for trisomy 21 or 1:150 for trisomy 18 or 13, she may choose between invasive and noninvasive prenatal testing after appropriate counseling on detection rates and risk. 3,4 In Denmark, the majority of women opt for invasive testing if the risk is high. 2,5 Cell-free noninvasive prenatal testing (cfNIPT) based on sequencing analysis of cell-free DNA has been widely implemented for screening of common aneuploidies and sex chromosomal aberrations (SCA). 6 However, a substantial number of fetal genetic disorders caused by subchromosomal copy

Purpose Proof of concept of the use of cell-based non-invasive prenatal testing (cbNIPT) as an alternative to chorionic villus sampling (CVS) following preimplantation genetic testing for monogenic disorders (PGT-M). Method PGT-M was performed by combined testing of short tandem repeat (STR) markers and direct mutation detection, followed by transfer of an unaffected embryo. Patients who opted for follow-up of PGT-M by CVS had blood sampled, from which potential fetal extravillous throphoblast cells were isolated. The cell origin and mutational status were determined by combined testing of STR markers and direct mutation detection using the same setup as during PGT. The cbNIPT results with respect to the mutational status were compared to those of genetic testing of the CVS. Results Eight patients had blood collected between gestational weeks 10 and 13, from which 33 potential fetal cell samples were isolated. Twenty-seven out of 33 isolated cell samples were successfully tested (82%), of which 24 were of fetal origin (89%). This corresponds to a median of 2.5 successfully tested fetal cell samples per case (range 1–6). All fetal cell samples had a genetic profile identical to that of the transferred embryo confirming a pregnancy with an unaffected fetus, in accordance with the CVS results. Conclusion These findings show that although measures are needed to enhance the test success rate and the number of cells identified, cbNIPT is a promising alternative to CVS. Trial registration number N-20180001

Introduction We identified risk factors and outcomes associated with SARS‐CoV‐2 infection in pregnancy in a universally tested population according to disease severity and validated information on SARS‐CoV‐2 during pregnancy in national health registers in Denmark. Material and methods Cohort study using data from national registers and medical records including all pregnancies between March 1, 2020 and February 28, 2021. We compared women with a validated positive SARS‐CoV‐2 test during pregnancy with non‐infected pregnant women. Risk factors and pregnancy outcomes were assessed by Poisson and Cox regression models and stratified according to disease severity defined by hospital admission status and admission reason (COVID‐19 symptoms or other). Using medical record data on actual period of pregnancy, we calculated predictive values of the SARS‐CoV‐2 diagnosis in pregnancy in the registers. Results SARS‐CoV‐2 infection was detected in 1819 (1.6%) of 111 185 pregnancies. Asthma was associated with infection (relative risk [RR] 1.63, 95% confidence interval [CI] 1.28–2.07). Risk factors for severe COVID‐19 disease requiring hospital admission were high body mass index (median ratio 1.06, 95% CI 1.04–1.09), asthma (RR 7.47, 95% CI 3.51–15.90) and gestational age at the time of infection (gestational age 28–36 vs < 22: RR 3.53, 95% CI 1.75–7.10). SARS‐CoV‐2‐infected women more frequently had hypertensive disorders in pregnancy (adjusted hazard ratio [aHR] 1.31, 95% CI 1.04–1.64), early pregnancy loss (aHR 1.37, 95% CI 1.00–1.88), preterm delivery before gestational age 28 (aHR 2.31, 95% CI 1.01–5.26), iatrogenically preterm delivery before gestational age 37 (aHR 1.49, 95% CI 1.01–2.19) and small‐for‐gestational age children (aHR 1.28, 95% CI 1.05–1.54). The associations were stronger among women admitted to hospital for any reason. The validity of the SARS‐CoV‐2 diagnosis in relation to pregnancy in the registers compared with medical records showed a negative predictive value of 99.9 (95% CI 99.9–100.0) and a positive predictive value of 82.1 (95% CI 80.4–83.7). Conclusions Women infected with SARS‐CoV‐2 during pregnancy were at increased risk of hypertensive disorders in pregnancy, early pregnancy loss, preterm delivery and having children small for gestational age. The validity of Danish national registers was acceptable for identification of SARS‐CoV‐2 infection during pregnancy.

This observational study investigated digital auscultation for the purpose of assessing the clinical feasibility of monitoring vascular sounds in pregnancy. The study was performed at the Regional Hospital Viborg, Denmark, and included 29 pregnant women, 10 non-pregnant women and 10 male participants. Digital auscultation was performed with an electronic stethoscope bilaterally near the uterine arteries and correlated to the clinical diagnosis of preeclampsia (PE), intrauterine growth restriction (IUGR) or normal pregnancy in the group of pregnant participants. In the group of non-pregnant participants, digital auscultation was performed as control measurements in the same anatomical positions. The auscultations displayed pulse waveforms comprising systolic and diastolic periods in 20 of the 29 pregnant participants. However, in the non-pregnant and male participants, the pulse waveforms were absent. The pulsatile patterns are thus likely to originate from the arteries in relation to the pregnant uterus. In the participants displaying pulse waveforms, the presence of a dicrotic notch appeared with a sensitivity of 89% and a specificity of 100% in the discrimination of normal pregnancies (n  =  11) from pregnancies with PE or IUGR (n  =  9), (p < 0.001). This preliminary study shows the potential of identifying vascular complications during pregnancy such as preeclampsia and intrauterine growth restriction. The morphology of the derived pulse contour should be investigated and could be further developed to identify pathophysiology.