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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 prediction of preeclampsia. Methods The study population consisted of pregnant women included in the PRESIDE study (Preeclampsia Screening in Denmark) 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 preeclampsia in a Danish population. For 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 8,386 pregnant women were included. The incidence of preeclampsia was 0.7% <37 weeks and 3.0% ≥37 weeks. In blood samples collected at 10 weeks’ gestation, multiples of the median (MoM) of PlGF were significantly lower in pregnancies with preeclampsia <37 weeks. However, PlGF MoM did not differ significantly between pregnancies with preeclampsia and unaffected pregnancies in samples collected before 10 weeks’ gestation. Conclusions Gestational age for PlGF samples might be expanded from 11–14 weeks to 10–14 weeks in risk assessment for preeclampsia using the FMF first trimester screening model. There is little evidence to support the use of PlGF collected before 10 weeks’ gestation., 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 prediction of preeclampsia.METHODS: The study population consisted of pregnant women included in the PRESIDE study (Preeclampsia Screening in Denmark) 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 preeclampsia in a Danish population. For 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 8,386 pregnant women were included. The incidence of preeclampsia was 0.7% <37 weeks and 3.0% ≥37 weeks. In blood samples collected at 10 weeks' gestation, multiples of the median (MoM) of PlGF were significantly lower in pregnancies with preeclampsia <37 weeks. However, PlGF MoM did not differ significantly between pregnancies with preeclampsia and unaffected pregnancies in samples collected before 10 weeks' gestation.CONCLUSIONS: Gestational age for PlGF samples might be expanded from 11-14 weeks to 10-14 weeks in risk assessment for preeclampsia using the FMF first trimester screening model. There is little evidence to support the use of PlGF collected before 10 weeks' gestation. This article is protected by copyright. All rights reserved.

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. Amo, 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

AIM: To evaluate a conservative estimate of the prevalence of chromosome conditions in all fetuses and children with a major congenital heart defect (CHD) in Denmark between 2008 and 2018.METHODS: This was a national register-based study including all singleton pregnancies with a pre- or postnatally diagnosed major CHD usually requiring surgery within the first year of life and a due date between July 2008 and December 2018 in Denmark. Data were retrieved from the Danish Fetal Medicine Database (DFMD) and the Danish Cytogenetic Central Register (DCCR) in the fall of 2020. The DCCR contains information on all prenatal and postnatal genetic analyses including karyotyping, chromosomal microarray, polymerase chain reaction, multiplex ligation-dependent probe amplification, and fluorescence in situ hybridization. All cases were reviewed by a clinical geneticist, and genetic changes were classified as pathogenic, likely pathogenic, uncertain significance, likely benign, and benign. Pathogenic and likely pathogenic were considered to be abnormal. Cases with a CHD without any registered chromosome analysis reported were considered genetically normal. Isolated CHD was defined as a case with a major CHD without any other structural malformations detected pre- or postnatally. Results were given as total numbers and frequencies. Comparison between isolated and non-isolated cases was performed using logistic regression analysis and presented as odds ratios (ORs) including 95% confidence intervals (CI).RESULTS: We retrieved 8,482 cases with any cardiovascular diagnosis from the DFMD and excluded twins (n=112) and minor CHD (n=6,921), resulting in 1,449 cases with major CHD. Of the included cases, 917 (63.3%) had a chromosome analysis performed with an abnormal test result in 186 cases, resulting in a prevalence of chromosomal conditions of 12.8% (95% confidence interval 11.2;14.7) in cases with major CHD. The highest prevalences were found in cases with pulmonary

Objective: To investigate prenatal changes in cardiac biometric and flow parameters in fetuses with bicuspid aortic valve (BAV) diagnosed neonatally compared with controls with normal cardiac anatomy. Methods: This analysis was conducted as part of the Copenhagen Baby Heart Study, a multicenter cohort study of 25 556 neonates that underwent second-trimester anomaly scan at 18 + 0 to 22 + 6 weeks' gestation and neonatal echocardiography within 4 weeks after birth, in Copenhagen University Hospital Herlev, Hvidovre Hospital and Rigshospitalet in greater Copenhagen, between April 2016 and October 2018. From February 2017 (Rigshospitalet) and September 2017 (Herlev and Hvidovre hospitals), the protocol for second-trimester screening of the heart was extended to include evaluation of the four-chamber view, with assessment of flow across the atrioventricular valves, sagittal view of the aortic arch and midumbilical artery and ductus venosus pulsatility indices. All images were evaluated by two investigators, and cardiac biometric and flow parameters were measured and compared between cases with BAV and controls. All cases with neonatal BAV were assessed by a specialist. Maternal characteristics and first- and second-trimester biomarkers were also compared between the two groups. Results: Fifty-five infants with BAV and 8316 controls with normal cardiac anatomy were identified during the study period and assessed using the extended prenatal cardiac imaging protocol. There were three times as many mothers who smoked before pregnancy in the group with BAV as in the control group (9.1% vs 2.7%; P = 0.003). All other baseline characteristics were similar between the two groups. Fetuses with BAV, compared with controls, had a significantly larger diameter of the aorta at the level of the aortic valve (3.1 mm vs 3.0 mm (mean difference, 0.12 mm (95% CI, 0.03–0.21 mm))) and the pulmonary artery at the level of the pulmonary valve (4.1 mm vs 3.9 mm (mean difference, 0.15 mm (95

Objective: The aim of this national study was to examine the incidence of preterm pre-eclampsia (PE) and the proportion of women with risk factors for PE, according to the criteria suggested by the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG), during a 10-year period in Denmark. Methods: Data from The Danish National Patient Registry and the Danish Medical Birth Registry were used to obtain the incidence of preterm PE with delivery < 37 weeks' gestation and risk factors for PE for all deliveries in Denmark from 1 January 2008 to 31 December 2017. The proportion of women with at least one high-risk factor and/or at least two moderate-risk factors for PE, according to the NICE and ACOG criteria, and the detection rate for preterm PE were examined. Race, socioeconomic status and the woman's weight at birth were not available from the registries used, and information on Type-2 diabetes was found to be invalid. Results: Of the 597 492 deliveries during the study period, any PE was registered in 3.2%, preterm PE < 37 weeks in 0.7% and early-onset PE < 34 weeks' gestation in 0.3%. These proportions remained largely unchanged from 2008 to 2017. Overall, the NICE criteria were fulfilled in 7.5% of deliveries and the ACOG criteria in 17.3%. In the total population, the NICE criteria identified 47.6% of those with preterm PE and the ACOG criteria identified 60.5%. The current criteria for offering aspirin treatment in Denmark largely correspond to having at least one NICE high-risk factor. In 2017, a total of 3.5% of deliveries had at least one NICE high-risk factor, which identified 28.4% of cases that later developed preterm PE. Conclusions: The incidence of preterm PE remained largely unchanged in Denmark from 2008 to 2017. Prediction of PE according to high-risk maternal factors could be improved by addition of moderate-risk factors.

Objective Exploring associations between antenatal detection of fetal growth restriction (FGR) and adverse outcome. Design Retrospective, observational, register-based study. Setting Zealand, Denmark. Population or sample Children born from 1 September 2012 to 31 August 2015. Methods Diagnoses from birth until 1 January 2018 were retrieved from The National Patient Registry. Detection was defined as estimated fetal weight less than the 2.3rd centile. Cox regression was used to associate detection status with the hazard rate of adverse outcome, adjusted for fetal weight deviation, maternal age, ethnicity, body mass index and smoking. Main outcome measures Adverse neonatal outcome, adverse neuropsychiatric outcome, respiratory disorders, endocrine disorders, gastrointestinal/urogenital disorders. Results A total of 2425 FGR children were included. An association was found for gastrointestinal/urogenital disorders (hazard ratio [HR] 1.68, 95% CI 1.26-2.23,P <0.001) and respiratory disorders (HR 1.22, 95% CI 1.02-1.46,P = 0.03) in detected versus undetected infants. For adverse neuropsychiatric outcome, HR was 1.32 (95% CI 1.00-1.75,P = 0.05). There was no evidence of an association between detection and adverse neonatal outcome (HR 1.00, 95% CI 0.62-1.61,P = 0.99) and endocrine disorders (HR 1.39, 95% CI 0.88-2.19,P = 0.16). Detected infants were smaller (median -28% versus -25%,P <0.0001), more often born preterm (odds ratio [OR] 4.15, 3.12-5.52,P <0.0001) and more often born after induction or caesarean section (OR 5.19, 95% CI 4.13-6.51,P <0.0001). Stillbirth risk was increased in undetected FGR fetuses (OR 2.63, 95% CI 1.37-5.04,P = 0.004). Conclusions We found an association between detection of FGR and risk of adverse childhood conditions, possibly caused by prematurity. Iatrogenic prematurity may be inevitable in stillbirth prevention, but is accompanied by a risk of long-term childhood conditions. Tweetable abstract Antenatal detection of growth