Risk factors for and pregnancy outcomes after SARS-CoV-2 in pregnancy according to disease severity: A nationwide cohort study with validation of the SARS-CoV-2 diagnosis.

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.

SARS-CoV-2 infection in pregnancy in Denmark-characteristics and outcomes after confirmed infection in pregnancy: A nationwide, prospective, population-based cohort study.

INTRODUCTION: Assessing the risk factors for and consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy is essential to guide clinical care. Previous studies on SARS-CoV-2 infection in pregnancy have been among hospitalized patients, which may have exaggerated risk estimates of severe outcomes because all cases of SARS-CoV-2 infection in the pregnant population were not included. The objectives of this study were to identify risk factors for and outcomes after SARS-CoV-2 infection in pregnancy independent of severity of infection in a universally tested population, and to identify risk factors for and outcomes after severe infection requiring hospital admission. MATERIAL AND METHODS: This was a prospective population-based cohort study in Denmark using data from the Danish National Patient Register and Danish Microbiology Database and prospectively registered data from medical records. We included all pregnancies between March 1 and October 31, 2020 and compared women with a positive SARS-CoV-2 test during pregnancy to non-infected pregnant women. Cases of SARS-CoV-2 infection in pregnancy were both identified prospectively and through register linkage to ensure that all cases were identified and that cases were pregnant during infection. Main outcome measures were pregnancy, delivery, maternal, and neonatal outcomes. Severe infection was defined as hospital admission due to coronavirus disease 2019 (COVID-19) symptoms. RESULTS: Among 82 682 pregnancies, 418 women had SARS-CoV-2 infection during pregnancy, corresponding to an incidence of 5.1 per 1000 pregnancies, 23 (5.5%) of which required hospital admission due to COVID-19. Risk factors for infection were asthma (odds ratio [OR] 2.19, 95% CI 1.41-3.41) and being foreign born (OR 2.12, 95% CI 1.70-2.64). Risk factors for hospital admission due to COVID-19 included obesity (OR 2.74, 95% CI 1.00-7.51), smoking (OR 4.69, 95% CI 1.58-13.90), infection after gestational age (GA) 22 weeks (GA 22-27 weeks: OR 3.77, 95% CI 1.16-12.29; GA 28-36 weeks: OR 4.76, 95% CI 1.60-14.12), and having asthma (OR 4.53, 95% CI 1.39-14.79). We found no difference in any obstetrical or neonatal outcomes. CONCLUSIONS: Only 1 in 20 women with SARS-CoV-2 infection during pregnancy required admission to hospital due to COVID-19. Risk factors for admission comprised obesity, smoking, asthma, and infection after GA 22 weeks. Severe adverse outcomes of SARS-CoV-2 infection in pregnancy were rare.

Cell-based non-invasive prenatal testing for monogenic disorders: confirmation of unaffected fetuses following preimplantation genetic testing.

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.

Cell-based noninvasive prenatal testing (cbNIPT) detects pathogenic copy number variations.

In two cases, cell-based noninvasive prenatal testing (cbNIPT) detected pathogenic copy number variations (CNVs) in the fetal genome. cbNIPT may potentially be an improved noninvasive alternative for the detection of smaller CNVs.

Association between maternal vascular murmur and the small-for-gestational-age fetus with abnormal umbilical artery Doppler flow.

OBJECTIVE: To investigate the association between maternal vascular murmurs (MVMs) and fetal growth restriction (defined as small-for-gestational-age [SGA] fetus) and abnormal Doppler pulsatility index (PI) of the uterine and/or umbilical arteries. METHODS: A cross-sectional study of women aged 18 years or older with a singleton pregnancy at 28-34 weeks was conducted at Regional Hospital Viborg, Denmark, between May 1 and August 1, 2013. Ultrasound fetal biometry was performed and the Doppler PI of the umbilical and uterine arteries was determined. An estimated fetal weight (EFW) at or below the 10th percentile was defined as SGA. Microphone recordings from the lower abdomen were divided into heart valve sounds and MVMs. RESULTS: The final analysis included 63 participants, with 25 classified as SGA and 38 as non-SGA. The mean pregnancy duration was 32.4 ± 1.4 weeks. In total, 17 participants had MVMs. There was a clear association between MVMs and a composite of SGA and an abnormal PI of the uterine and/or the umbilical artery (P<0.001), but not between MVMs and SGA only (P=0.154). CONCLUSION: Maternal vascular murmurs are significantly associated with fetal growth restriction, but not with SGA per se.

Separation and characterization of maternal cardiac and vascular sounds in the third trimester of pregnancy.

OBJECTIVE: To characterize the vascular sounds of the uteroplacental blood flow obtained by microphones. METHODS: The present retrospective study took place in an anechoic chamber facility at Aalborg University, Aalborg, Denmark, in 2012, and included pregnant participants aged 18-40 years with a singleton pregnancy at 32-36 weeks and a parity of 0-2. Abdominal Doppler ultrasonography was performed bilaterally on the uterine arteries. Subsequently, in the same positions, sound recordings were performed with microphones. The derived raw sound signal was separated into two frequency ranges, and characterized accordingly. RESULTS: The mean pregnancy length among 25 participants was 33.6 ± 2.0 weeks. The pulsatility index of the uterine artery was 0.67 ± 0.24. All 50 recordings displayed the first and second maternal heart sounds (frequency 25-100 Hz), and in 17 of 50 recordings, maternal vascular murmurs (frequency 200-800 Hz) were present. The average pulse wave velocity between the maternal aortic valve and the uterine artery was estimated to be 6.6 ± 1.5 m/s. CONCLUSION: Maternal vascular murmurs in the frequency range of 200-800 Hz were identified as a possible marker of abnormal uteroplacental blood flow, and provide a means to measure the arterial pulse wave velocity.

Digital auscultation of the uterine artery: a measure of uteroplacental perfusion.

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.

No change in adolescents' neglect on contraceptive use over two decades.

PURPOSE: The sexual activity and contraceptive use is evaluated over 21 years amongst Danish adolescents in ninth grade. METHODS: A repeated, cross-sectional questionnaire study in the municipality of Viborg, comparing the results of four consecutive surveys between 1986 and 2007. RESULTS: In 2007, 40% of the pupils had sexual debut at an average age of 15.3 ± 1.5 years. At sexual debut condoms were used in 77% of the adolescents and the contraceptive pill in 15%. At their latest coitus 34% used any contraceptive pill as 27% of pupils changed from use of condom to the pill. Practical experience with condoms was found in 90% of both sexes at sexual debut. Fourteen percent of the adolescents used no contraception at all at debut in 2007, which is similar to 1986, 1993, and 2000. Eighteen percent of the pupils used no contraception at all at their last intercourse in 2007 and 2000. CONCLUSION: Knowledge about and use of condoms is substantial amongst adolescents already at sexual debut. A shift is confirmed from condoms at first coitus to more frequent use of the pill later on. A considerable number of pupils (10-20%) are neither protected against sexually transmitted infections nor pregnancy at first or later intercourse.

[Down's syndrome risk assessment in Denmark--secondary publication]. / Risikovurdering for Downs syndrom i Danmark--sekundaerpublikation.

In 2004 The Danish National Board of Health introduced a new guideline regarding prenatal screening. All pregnant women are now offered a Down's syndrome risk assessment. The new guideline has had an impact on the number of invasive early prenatal procedures. The number of procedures fell by 50% from 2000 to 2006. 90% of the foetuses with Down's syndrome are detected prenatally. Denmark is one of the first countries in the world in which risk assessment for Down's syndrome has been successfully implemented at a national level.

[Basic registration of risk factors in medical records. Malnutrition, overweight, physical inactivity, smoking and alcohol]. / Basale journaloplysninger om risikofaktorer. Underernaering, overvaegt, fysisk inaktivitet, rygning og alkohol.

INTRODUCTION: Lifestyle factors are important for clinical outcome. Systematic and early identification of these factors is important in order to offer relevant lifestyle intervention programmes. The objective was to evaluate whether basic registration of risk factors was understandable, applicable and sufficient in the clinical workday. MATERIALS AND METHODS: Eleven clinical specialists participated from a broad range of departments. They performed identification and registration of malnutrition, overweight, physical inactivity, smoking and harmful alcohol consumption based on medical records from own departments (in total 2420 times). The specialists then evaluated the understanding, applicability and sufficiency (363 times). Their comments were noted. RESULTS: Identification and registration was accomplished for 85% (0-100%) of the records. Except for two fields--"measurements of waist" and "other training programs"--the specialists found the basic registration understandable, applicable and sufficient. They lacked more details regarding stress-response in the information material and pointed out inconsistencies in the wording. Ten specialists found that the recommended clinical approach was possible to implement in the present routines. CONCLUSION: Basic registration of lifestyle factors for adult patients is possible and clinical relevant. It is recommended that the Danish National Board of Health uses the results in future.

User driven, evidence based experimental design; a new method for interface design used to develop an interface for clinical overview of patient records.

A novel method of interface design--user driven, evidence based experimental design--was developed which approximates the usual clinical way of maturing science and technology in the healthcare domain. The method is user-driven and the clinician remains in control of gathering and evaluating evidence of relevance to the project--as well as specifying the details of the user interface. Information not obtainable from the literature was gained experimentally and used to achieve a deeper understanding of the problem before the design phase. The design was subsequently validated experimentally by ordinary users with no connection to the software or design team. After applying this method to the problem of gaining a satisfactory clinical overview of a single patient's record, we recommend that clinical IT interfaces have clinical logic, sufficient complexity, and are well structured. Developers should use computer power to support "building blocks" such as anatomical problem lists and summaries of history, status and treatment, personal notes, and should support clinical browsing using text and graphics.