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Objectives: To investigate the predictive performance of the Fetal Medicine Foundation (FMF) first‐trimester screening algorithm for pre‐eclampsia in a Danish population and compare screening performance with that of the current Danish strategy, which is based on maternal risk factors. Methods: This was a prospective study of women with a singleton pregnancy attending for their first‐trimester ultrasound scan and screening for aneuploidies at six Danish university hospitals between May 2019 and December 2020. Prenatal data on maternal characteristics and medical history were recorded, and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA‐PI), serum pregnancy‐associated plasma protein‐A (PAPP‐A) and serum placental growth factor (PlGF) were collected without performing a risk assessment for pre‐eclampsia. Information on acetylsalicylic acid use was recorded. After delivery, pregnancy outcome, including gestational age at delivery and pre‐eclampsia diagnosis, was recorded. Pre‐eclampsia risk assessment for each woman was calculated blinded to outcome using the FMF screening algorithm following adjustment to the Danish population. Detection rates (DRs) of the FMF algorithm were calculated for a fixed screen‐positive rate (SPR) of 10% and for the SPR achieved in the current Danish screening. Results: A total of 8783 pregnant women were included, with a median age of 30.8 (interquartile range (IQR), 28.1–33.9) years. The majority were white (95%), naturally conceiving (90%), non‐smokers (97%) and had no family history of pre‐eclampsia (96%). The median body mass index was 23.4 (IQR, 21.2–26.6) kg/m2. A complete risk assessment including maternal characteristics, MAP, UtA‐PI, PlGF and PAPP‐A was available for 8156 women (92.9%). In these women, UtA‐PI was measured bilaterally with a median value of 1.58 (IQR, 1.27–1.94) and the median resting MAP of 80.5 (IQR, 76.1–85.4) mmHg in two consecutive measurements. Among these, 303 (3.7%) developed pre‐eclampsia, including 55 (0.7%) cases of pre‐eclampsia with delivery < 37 weeks of gestation and 16 (0.2%) cases of pre‐eclampsia with delivery < 34 weeks. At a SPR of 10%, combined screening using the FMF algorithm based on maternal characteristics, MAP, UtA‐PI, PlGF and PAPP‐A had a DR of 77.4% (95% CI, 57.6–97.2%) for pre‐eclampsia with delivery < 34 weeks, 66.8% (95% CI, 54.4–79.1%) for pre‐eclampsia with delivery < 37 weeks and 44.1% (95% CI, 38.5–49.7%) for pre‐eclampsia with delivery at any gestational age. The current Danish screening strategy using maternal risk factors detected 25.0% of women with pre‐eclampsia with delivery < 34 weeks and 19.6% of women with pre‐eclampsia with delivery < 37 weeks at a SPR of 3.4%. When applying the FMF algorithm including maternal characteristics, MAP, UtA‐PI and PlGF at the fixed SPR of 3.4%, the DRs were 60.5% (95% CI, 36.9–84.1%) for PE with delivery < 34 weeks and 45.2% (95% CI, 32.0–58.5%) for PE with delivery < 37 weeks. Conclusion: In this large Danish multicenter study, the FMF algorithm based on maternal characteristics, MAP, UtA‐PI, PlGF and PAPP‐A predicted 77.4% of cases with pre‐eclampsia with delivery < 34 weeks and 66.8% of cases with pre‐eclampsia with delivery < 37 weeks of gestation at a SPR of 10%, suggesting that the performance of the algorithm in a Danish cohort matches that in other populations. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: The primary aim of this study was to compare the screening performance for trisomy 21 (T21) between combined first-trimester screening (cFTS) with referral for invasive testing at a T21 risk ≥ 1 in 300, and contingent screening consisting of referral for invasive testing at a cFTS-T21 risk ≥ 1 in 100 and referral for cell-free DNA (cfDNA) testing at a cFTS-T21 risk between 1 in 100 and 1 in 1000. Secondary aims were to compare the incidence of fetuses diagnosed with trisomy 18 (T18), trisomy 13 (T13) or sex chromosome aneuploidy, and examine the association between fetal fraction of cfDNA in maternal blood and maternal/fetal characteristics.Methods: Women with a singleton pregnancy and a cFTS-T21 risk of ≥ 1 in 1000 were recruited consecutively from two Danish hospitals between August 2014 and May 2015. First-trimester combined screening was based on maternal age, nuchal translucency thickness and levels of pregnancy-associated plasma protein A (PAPP-A) and β-human chorionic gonadotropin (β-hCG). Blood samples for cfDNA testing were analyzed for risks of T21, T18, T13 and sex chromosomal aneuploidies. cfDNA analysis was conducted blinded to the cFTS assessment and karyotype results. Pregnancy outcomes and pre- and postnatal karyotypes were obtained from the Danish Fetal Medicine Database.Results: Among 6449 women who underwent cFTS risk assessment, 869 (13.5%) had a T21 risk of ≥ 1 in 1000 and 597 were included for cfDNA testing. Among these, there were 15 cases of T21, one case of T18 and two cases of T13. The sensitivity for detection of T21 was 100% using both screening strategies, while specificity increased significantly (P < 0.0001) from 97.0% using the cFTS strategy to 98.8% using the contingent approach. The sensitivity for detection of T21, T18 and T13 increased from 94.4% using the cFTS strategy to 100% using the contingent approach, with overlapping CIs, while specificity increased significantly (P < 0.0001) from 97.1% for cFTS to 98.9% for the contingent strategy. Seven pregnancies were categorized as being at increased risk of a sex chromosomal aneuploidy by cfDNA testing but chromosome analysis was discordant, corresponding to a false-positive rate of 1.2%. The fetal fraction decreased significantly with increasing maternal weight and increased significantly with the level of β-hCG and PAPP-A and among female fetuses, in both univariate and multivariate analyses.Conclusions: In a clinical setting with efficient cFTS, contingent screening offering women with a cFTS risk of ≥ 1 in 100 an invasive test and women with a risk from 1 in 100 to 1 in 1000 a cfDNA test had the same sensitivity for T21, T18 and T13, but significantly increased specificity, when compared with offering an invasive test to all women with a risk of ≥ 1 in 300. Implementing contingent screening would therefore reduce significantly the number of invasive tests performed at no loss of sensitivity. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess prospectively the risk of fetal loss associated with chorionic villus sampling (CVS) and amniocentesis (AC) following combined first-trimester screening (cFTS) for Down syndrome.Methods: This was a nationwide population-based study (Danish Fetal Medicine Database, 2008-2010) including 147,987 women with singleton pregnancy who underwent cFTS. Propensity score stratification was used to assess the risk of fetal loss with and without invasive testing. Analyses were performed between 3 and 21 days after cFTS for CVS and between 28 and 42 days after cFTS for AC. Results are reported as average risk differences with 95% CIs.Results: The risks of miscarriage and stillbirth were not higher in women exposed to CVS or AC compared with unexposed women, independent of the analysis time-point. The average effect of CVS on risk of miscarriage was -0.08% (95% CI, -0.64; 0.47) at 3 days and -0.21% (95% CI, -0.58; 0.15) at 21 days after cFTS, while the effect on risk of stillbirth was -0.18% (95% CI, -0.50; 0.13) at 3 days and -0.27% (95% CI, -0.58; 0.04) at 21 days after cFTS. Regarding the effect of AC on risk of miscarriage, the analysis at 28 days after cFTS showed an average effect of 0.56% (95% CI, -0.21; 1.33), while the effect on risk of stillbirth was 0.09% (95% CI, -0.39; 0.58) at 42 days after cFTS.Conclusion: Neither CVS nor AC was associated with increased risk of miscarriage or stillbirth. These findings indicate that the procedure-related risk of CVS and AC is very low. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusions To assess the validity of the Fetal Medicine Foundation (FMF) chorionicity‐specific models for fetal growth in twin pregnancy.This was an external validation study of the FMF models using a nationwide Danish cohort of twin pregnancies. The cohort included all dichorionic (DC) and monochorionic diamniotic (MCDA) twin pregnancies with an estimated delivery date between 2008 and 2018, which satisfied the following inclusion criteria: two live fetuses at the first‐trimester ultrasound scan (11–14 weeks' gestation); biometric measurements available for the calculation of estimated fetal weight (EFW) using the Hadlock‐3 formula; and delivery of two liveborn infants. Validation involved assessing the distributional properties of the models and estimating the mean EFW Z‐score deviations. Additionally, the models were applied to pregnancies that delivered preterm and attended non‐scheduled visits (complicated pregnancies).Overall, 8542 DC and 1675 MCDA twin pregnancies met the inclusion criteria. In DC twins, 17 084 fetuses were evaluated at a total of 95 346 ultrasound scans, of which 44.5% were performed at scheduled visits in pregnancies carried to 37 + 0 weeks or later. The median number of growth scans per DC twin fetus from 20 + 0 weeks onwards was four. The model showed good agreement with the validation cohort for scheduled visits in DC twins delivered at 37 + 0 weeks or later (mean EFW Z‐score, –0.14 ± 1.05). In MCDA twins, 3350 fetuses underwent 31 632 eligible ultrasound scans, of which 59.5% were performed at scheduled visits in pregnancies carried to 36 + 0 weeks or later. The median number of growth scans per MCDA twin fetus from 16 + 0 weeks onwards was 10. The model showed favorable agreement with the validation cohort for scheduled visits in MCDA twins delivered at 36 + 0 weeks or later (mean EFW Z‐score, –0.09 ± 1.01). Non‐scheduled visits and preterm delivery before 37 + 0 weeks for DC twins and before 36 + 0 weeks for MCDA twins corresponded with smaller weight estimates, which was consistent with the study's definition of complicated pregnancy.The FMF models provide a good fit for EFW measurements in our Danish national cohort of uncomplicated twin pregnancies assessed at routine scans. Therefore, the FMF models establish robust criteria for subsequent investigations and potential clinical applications. Future research should focus on exploring the consequences of clinical implementation, particularly regarding the identification of twins that are small‐for‐gestational age, as they are especially susceptible to adverse perinatal outcome. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

An abstract of the article "Vaginal progesterone and the risk of preterm delivery in high-risk twin gestations - secondary analysis of a placebo-controlled randomized trial" by K. Klein and colleagues is presented.

Objectives: To describe the distributional properties and assess the performance of placental growth factor (PlGF) measured in blood samples collected before 11 weeks' gestation in the prediction of pre-eclampsia (PE)., Methods: The study population consisted of pregnant women included in the Pre-eclampsia Screening in Denmark (PRESIDE) study with a PlGF measurement from the routine combined first-trimester screening (cFTS) blood sample collected at 8-14 weeks' gestation. PRESIDE was a prospective multicenter study investigating the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for PE in a Danish population. In the current study, serum concentration of PlGF in the cFTS blood samples was analyzed in batches between January and June 2021., Results: A total of 8386 pregnant women were included. The incidence of PE was 0.7% at < 37 weeks' gestation and 3.0% at ≥ 37 weeks. In blood samples collected at 10 weeks' gestation, PlGF multiples of the median (MoM) were significantly lower in pregnancies with preterm PE < 37 weeks compared to unaffected pregnancies. However, PlGF MoM did not differ significantly between pregnancies with PE and unaffected pregnancies in samples collected before 10 weeks' gestation., Conclusions: The gestational-age range for PlGF sampling may be expanded from 11-14 to 10-14 weeks when assessing the risk for PE using the FMF first-trimester screening model. There is little evidence to support the use of PlGF in blood samples collected before 10 weeks' gestation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To examine the association of isolated single umbilical artery (iSUA) confirmed at the mid-trimester anomaly scan and adverse pregnancy outcome and congenital malformations with up to 10 years postnatal follow up., Methods: This retrospective cohort study included 116,501 singleton pregnancies consecutively enrolled in first trimester screening for aneuploidies and mid-trimester anomaly scan at three University Hospitals in the Capital Region of Copenhagen, Denmark.Data from the Danish Fetal Medicine Database (2008-2017) were verified by manually scrutinizing pre- and postnatal records. The main outcomes of interest were intrauterine fetal demise (IUFD), small for gestational age (SGA), preterm delivery, cesarean section and unrecognized pre- and postnatal congenital malformations., Results: In total, 775 pregnancies with iSUA were identified. Isolated SUA were associated with a significantly increased risk of IUFD (OR 4.16, 95% CI 2.06-8.44), SGA < 3 rd centile (aOR 2.41, 95% 1.85-3.14) and SGA < 10 th centile (aOR 1.84, 95% CI 1.53-2.21), but not with preterm delivery or cesarean section. The laterality of the missing artery was not associated with SGA. In total, 4.3% of pregnancies with iSUA had unrecognized congenital malformations. 1.5% with iSUA had congenital cardiovascular malformations, which were considered minor., Conclusion: Isolated SUA is associated with IUFD and SGA, supporting surveillance during third trimester. If, during the mid-trimester scan, the sonographer achieves thorough, extended cardiac views and finds no additional malformation other than SUA, fetal echocardiography seems not to be needed.

Objectives: The objective of this analysis was to evaluate the effect of a diet rich in animal protein and low in glycemic index on blood pressure during pregnancy., Design: This post hoc , secondary data analysis of a randomized controlled trial, evaluated blood pressure in pregnant participants who were randomized either to an ad libitum diet with high protein and low glycemic index, rich in dairy and seafood, or an ad libitum control diet according to national recommendations., Setting: The study occurred in pregnant women in Copenhagen, Denmark., Sample: A total of 279 pregnant females with overweight or obesity were enrolled., Methods and Outcome Measure: Blood pressure was measured at 5 timepoints during pregnancy from gestational week 15 through week 36, and blood pressure between groups was compared., Results: There were no differences between diet arms in systolic or diastolic blood pressure over time. There were also no differences in most blood-pressure-related pregnancy complications, including the prevalence of premature birth, preeclampsia, or hypertension, but the frequency of total cesarean sections was lower in the active than the control group (16 out of 104 vs. 30 out of 104) ( p  = 0.02)., Conclusion: Increased animal protein intake was not associated with changes in blood pressure in pregnant women with overweight or obesity., Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT01894139]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Larson, Magkos, Zingenberg, Svare, Astrup and Geiker.)

Objective: To examine the association of gestational weight gain (GWG) among women with pre-pregnancy overweight or obesity with infant weight and BMI z-score at birth., Methods: This study is a secondary analysis of a randomized controlled trial including data from 208 infants at birth born by mothers with pre-pregnancy BMI between 28 and 45 kg/m 2 who completed the APPROACH study (randomized to a high-protein low-glycemic index diet or a moderate-protein moderate-glycemic index diet). This analysis pooled the two diet treatment groups together and data were analyzed using a linear mixed model., Results: Limiting GWG by 1 kg was associated with lower birthweight (-16 g, P  = 0.003), BMI z-score (-0.03SD, P  = 0.019), weight z-score (-0.03SD, P  = 0.004), and infant abdominal circumference (-0.06 cm, P  = 0.039). Infants born by mothers whose GWG was ≤9 kg weighed less (122 g, 95% CI: 6-249, P  = 0.040), had similar BMI z-score (0.2SD, 95% CI: -0.06 to 0.55, P  = 0.120), and lower incidence of emergency cesarean deliveries (11.5% vs. 23.1%, P  = 0.044) compared to infants born by mothers whose GWG was >9 kg. When women were classified into GWG quartiles, women in Q1 (GWG range: -7.0 to 3.2 kg) gave birth to smaller infants (3,420 g, P  = 0.015) with lower BMI z-score (-0.5SD, P  = 0.041) than women in Q2 (3.3-7.1 kg), Q3 (7.2-10.9 kg) and Q4 (11.1-30.2 kg)., Conclusions: Limiting GWG among women with pre-pregnancy overweight or obesity was associated with lower infant weight, BMI z-score, weight z-score, and abdominal circumference at birth. Moreover, GWG below the Institute of Medicine guideline of a maximum of 9 kg was associated with lower birthweight and fewer emergency cesarean deliveries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Mogensen, Zingenberg, Svare, Astrup, Magkos and Geiker.)