First Trimester Contingent Screening for Aneuploidies with Cell-Free Fetal DNA in Singleton Pregnancies - a Swiss Single Centre Experience.

Introduction: Switzerland was amongst the first countries to offer cell-free fetal DNA (cffDNA) testing covered by the health insurance to pregnant women with a risk ≥ 1:1000 for trisomies at first trimester combined screening (FTCS). The aim of this study is to evaluate the implementation of this contingent model in a single tertiary referral centre and its effect on gestational age at diagnosing trisomy 21. Materials and Methods: Between July 2015 and December 2020 all singleton pregnancies at 11-14 weeks of gestation without major fetal malformation were included and stratified according to their risk at FTCS. Statistical analysis was performed by GraphPad Version 9.1 for Windows. Results: 4424 pregnancies were included. Of 166 (3.8%) pregnancies with a NT ≥ 3.5 mm and/or a risk ≥ 1:10 at FCTS, 130 (78.3%) opted for direct invasive testing. 803 (18.2%) pregnancies had an intermediate risk, 692 (86.2%) of them opted for cffDNA first. 3455 (78.1%) pregnancies had a risk < 1:1000. 63 fetuses were diagnosed with trisomy 21, 47 (74.6%) directly by invasive procedures after FTCS, 16 (25.4%) by cffDNA first. Conclusions: Most women choose cffDNA or invasive testing as second tier according to national guidelines. Despite the delay associated with cffDNA testing after FCTS, 75% of all trisomy 21 are still diagnosed in the first trimester with this contingent screening model.

Fetal Assessment in Pregnancy (Indication and Methodology for Fetal Monitoring in a low-risk Population). Guideline of the DGGG, DEGUM, OEGGG and SGGG (S3-Level, AWMF Registry No. 015/089, February 2023). / Fetale Überwachung in der Schwangerschaft (Indikation und Methodik zur fetalen Zustandsdiagnostik im Low-Risk-Kollektiv). Leitlinie der DGGG, DEGUM, OEGGG und SGGG (S3-Level, AWMF-Registernummer 015/089, Februar 2023).

PURPOSE: The aim of this guideline was to find evidence on whether carrying out Doppler examinations and CTGs in low-risk cohorts of pregnant women improves outcomes. METHODS: First, a systematic search for guidelines was carried out. Identified guidelines were evaluated using the DELPHI instrument of the AWMF. Three guidelines were found to be suitable to evaluate CTG. Two DEGUM best practice guidelines were judged suitable to describe the methods. All studies on this issue were additionally analyzed using 8 PICO questions. A structured consensus of the participating professional societies was achieved using a nominal group process and a structured consensus conference moderated by an independent moderator. RECOMMENDATIONS: No antepartum Doppler sonography examinations should be carried out in low-risk cohorts in the context of antenatal care. No antepartum CTG should be carried out in low-risk cohorts. NOTE: The guideline will be published simultaneously in the official journals of both professional societies (i. e., Geburtshilfe und Frauenheilkunde for the DGGG and Ultraschall in der Medizin/European Journal of Ultrasound for the DEGUM).

Maternal overweight and obesity and its association with metabolic changes and fetal overgrowth in the absence of gestational diabetes mellitus: A prospective cohort study.

INTRODUCTION: Previous studies indicated an association between fetal overgrowth and maternal obesity independent of gestational diabetes mellitus (GDM). However, the underlying mechanisms beyond this possible association are not completely understood. This study investigates metabolic changes and their association with fetal and neonatal biometry in overweight and obese mothers who remained normal glucose-tolerant during gestation. MATERIAL AND METHODS: In this prospective cohort study 893 women who did not develop GDM were categorized according to their pregestational body mass index (BMI): 570 were normal weight, 220 overweight and 103 obese. Study participants received a broad metabolic evaluation before 16 weeks and were followed up until delivery to assess glucose levels during the oral glucose tolerance test (OGTT) at mid-gestation as well as fetal biometry in ultrasound and pregnancy outcome data. RESULTS: Increased maternal BMI was associated with an adverse metabolic profile at the beginning of pregnancy, including a lower degree of insulin sensitivity (as assessed by the quantitative insulin sensitivity check index) in overweight (mean difference: -2.4, 95% CI -2.9 to -1.9, p < 0.001) and obese (mean difference: -4.3, 95% CI -5.0 to -3.7, p < 0.001) vs normal weight women. Despite not fulfilling diagnosis criteria for GDM, overweight and obese mothers showed higher glucose levels at fasting and during the OGTT. Finally, we observed increased measures of fetal subcutaneous tissue thickness in ultrasound as well as higher proportions of large-for-gestational-age infants in overweight (18.9%, odds ratio [OR] 1.74, 95% CI 1.08-2.78, p = 0.021) and obese mothers (21.0%, OR 1.99, 95% CI 1.06-3.59, p = 0.027) vs normal weight controls (11.8%). The risk for large for gestational age was further determined by OGTT glucose (60 min: OR 1.11, 95% CI 1.02-1.21, p = 0.013; 120 min: OR 1.13, 95% CI 1.02-1.27, P = 0.025, for the increase of 10 mg/dL) and maternal triglyceride concentrations (OR 1.11, 95% CI 1.01-1.22, p = 0.036, for the increase of 20 mg/dL). CONCLUSIONS: Mothers affected by overweight or obesity but not GDM had a higher risk for fetal overgrowth. An impaired metabolic milieu related to increased maternal BMI as well as higher glucose levels at mid-gestation may impact fetal overgrowth in women still in the range of normal glucose tolerance.

Fetal Assessment in Pregnancy (Indication and Methodology for Fetal Monitoring in a Low-risk Population). Guideline of the DGGG, DEGUM, OEGGG and SGGG (S3-Level, AWMF Registry No. 015/089, February 2023).

Purpose The aim of this guideline was to find evidence on whether carrying out Doppler examinations and CTGs in low-risk cohorts of pregnant women improves outcomes. Methods First, a systematic search for guidelines was carried out. Identified guidelines were evaluated using the DELPHI instrument of the AWMF. Three guidelines were found to be suitable to evaluate CTG. Two DEGUM best practice guidelines were judged suitable to describe the methods. All studies on this issue were additionally analyzed using 8 PICO questions. A structured consensus of the participating professional societies was achieved using a nominal group process and a structured consensus conference moderated by an independent moderator. Recommendations No antepartum Doppler sonography examinations should be carried out in low-risk cohorts in the context of antenatal care. No antepartum CTG should be carried out in low-risk cohorts. Note The guideline will be published simultaneously in the official journals of both professional societies (i.e., Geburtshilfe und Frauenheilkunde for the DGGG and Ultraschall in der Medizin/European Journal of Ultrasound for the DEGUM).

Diverse mechanisms underlying the fetal growth course in gastroschisis and omphalocele.

BACKGROUND: Gastroschisis and omphalocele are the 2 most common congenital fetal abdominal wall defects. Both malformations are commonly associated with small-for-gestational-age neonates. However, the extent and causes of growth restriction remain controversial in both gastroschisis and omphalocele without associated malformations or aneuploidy. OBJECTIVE: This study aimed to examine the role of the placenta and the birthweight-to-placental weight ratio in fetuses with abdominal wall defects. STUDY DESIGN: This study included all cases of abdominal wall defects examined at our hospital between January 2001 and December 2020, retrieving the data from the hospital's software. Fetuses with any other combined congenital anomalies, known chromosomal abnormalities, or lost to follow-up were excluded. Overall, 28 singleton pregnancies with gastroschisis and 24 singleton pregnancies with omphalocele met the inclusion criteria. Patient characteristics and pregnancy outcomes were reviewed. The primary outcome was to investigate the association between birthweight and placental weight in pregnancies with abdominal wall defects as measured after delivery. To correct for gestational age and to compare total placental weights, ratios between the observed and expected birthweights for the given gestational age in singletons were calculated. The scaling exponent ß was compared with the reference value of 0.75. Statistical analysis was performed using GraphPad Prism (version 8.2.1; GraphPad Software, San Diego, CA) and IBM SPSS Statistics. A P value of <.05 indicated statistical significance. RESULTS: Women pregnant with a fetus with gastroschisis were significantly younger and more often nulliparous. In addition, in this group, the gestational age of delivery was significantly earlier and almost exclusively for cesarean delivery. Of 28 children, 13 (46.7%) were born small for gestational age, only 3 of them (10.7%) had a placental weight <10th percentile. There is no correlation between birthweight percentiles and placental weight percentiles (P=not significant). However, in the omphalocele group, 4 of 24 children (16.7%) were born small for gestational age (<10th percentile), and all children also had a placental weight <10th percentile. There is a significant correlation between birthweight percentiles and placental weight percentiles (P<.0001). The birthweight-to-placental weight ratio differs significantly between pregnancies diagnosed with gastroschisis and pregnancies diagnosed with omphalocele (4.48 [3.79-4.91] vs 6.05 [5.38-6.47], respectively; P<.0001). Allometric metabolic scaling revealed that placentas complicated by gastroschisis and placentas complicated by omphalocele do not scale with birthweight. CONCLUSION: Fetuses with gastroschisis displayed impaired intrauterine growth, which seemed to differ from the classical placental insufficiency growth restriction.

Implementing Preeclampsia Screening in Switzerland (IPSISS): First Results from a Multicentre Registry.

INTRODUCTION: The Fetal Medicine Foundation (FMF) London developed a first trimester combined screening algorithm for preterm preeclampsia (pPE) that allows a significantly higher detection of pregnancies at risk compared to conventional screening by maternal risk factors only. The aim of this trial is to validate this screening model in the Swiss population in order to implement this screening into routine first trimester ultrasound and to prescribe low-dose aspirin 150 mg (LDA) in patients at risk for pPE. Therefore, a multicentre registry study collecting and screening pregnancy outcome data was initiated in 2020; these are the preliminary results. METHODS: Between June 1, 2020, and May 31, 2021, we included all singleton pregnancies with pPE screening at the hospitals of Basel, Lucerne, and Bern. Multiple of medians of uterine artery pulsatility index (UtA-PI), mean arterial pressure (MAP), placental growth factor (PlGF), and pregnancy-associated plasma protein A (PAPP-A) as well as risks were analysed as calculated by each centre's software and recalculated on the FMF online calculator for comparative reasons. Statistical analyses were performed by GraphPad Version 9.1. RESULTS: During the study period, 1,027 patients with singleton pregnancies were included. 174 (16.9%) had a risk >1:100 at first trimester combined screening. Combining the background risk, MAP, UtA-PI, and PlGF only, the cut-off to obtain a screen positive rate (SPR) of 11% is ≥1:75. Outcomes were available for 968/1,027 (94.3%) of all patients; 951 resulted in live birth. Fifteen (1.58%) developed classical preeclampsia (PE), 23 (2.42%) developed PE according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) definition. CONCLUSION: First trimester combined screening for PE and prevention with LDA results in a low prevalence of PE. The screening algorithm performs according to expectations; however, the cut-off of >1:100 results in a SPR above the accepted range and a cut-off of ≥1:75 should be considered for screening. More data are needed to evaluate, if these results are representative for the general Swiss population.

Use of Polynomial Reference Ranges for Atrioventricular Intervals Assessed by Fetal Echocardiography in Anti-Ro/SSA Antibody-Positive Pregnancies to Exclude Fetal Heart Blocks: A Pilot Study.

INTRODUCTION: Maternal anti-Ro/SSA antibodies can cause fetal atrioventricular blocks (AVB). This pilot study aims to apply previously published echocardiographic reference ranges of the fetal atrioventricular (AV) intervals in the setting of anti-Ro/SSA antibody-positive pregnancies in order to exclude a 1° AVB. MATERIALS AND METHODS: Between January 2018 and September 2022, we included all women with known anti-Ro/SSA antibodies followed up at the prenatal ultrasound department of the University Hospital of Bern. AV intervals were serially measured by two previously reported methods and plotted against previously created reference ranges. RESULTS: We included 23 pregnancies from 17 anti-Ro/SSA antibody-positive women with connective tissue diseases. 443 AV interval measurements were recorded between 16+3 and 38+4 weeks of gestation. 14 (3.2%) AV-intervals measured >150 ms, none measured >170 ms and 8 (1.8%) were found to be >95th percentile. In none of the pregnancies, serial AV-prolongations were noted. The postnatal electrocardiograms demonstrated normal sinus rhythm without AVB in all children. CONCLUSION: AV intervals of pregnancies followed up for anti-Ro/SSA antibodies without neonatal AVB lie within our published polynomial reference ranges. While diagnosing a 1° AVB remains controversial, more data are needed to prove that our reference ranges are helpful exclude a 1° AVB.

First-trimester glycosylated hemoglobin (HbA1c) and maternal characteristics in the prediction of gestational diabetes: An observational cohort study.

INTRODUCTION: This study aimed to investigate the extent to which gestational diabetes mellitus (GDM) can be predicted in the first trimester by combining a marker of growing interest, glycosylated hemoglobin A1c (HbA1c), and maternal characteristics. MATERIAL AND METHODS: This observational study was conducted in the outpatient obstetric department of our institution. The values of HbA1c and venous random plasma glucose were prospectively assessed in the first trimester of pregnancy. We determined maternal characteristics that were independent predictors from the regression analysis and calculated areas under the receiver-operating curves by combining the maternal age, body mass index, previous history of GDM, and first-degree family history for diabetes mellitus. Moreover we investigated the predictive capability of HbA1c to exclude GDM. Patients with a first-trimester HbA1c level of 6.5% (48 mmol/mol) or more were excluded. The study was registered at ClinicalTrials.gov ID: NCT02139254. RESULTS: We included 785 cases with complete dataset. The prevalence of GDM was 14.7% (115/785). Those who developed GDM had significantly higher HbA1c and random plasma glucose values (p < 0.0001 and p = 0.0002, respectively). In addition, they had a higher body mass index, were more likely to have a history of GDM and/or a first-degree family history of diabetes. When these maternal characteristics were combined with the first-trimester HbA1c and random plasma glucose the combined area under the receiver operating characteristics curve was 0.76 (95% CI 0.70-0.81). CONCLUSIONS: Our results indicate that HbA1c and random plasma glucose values combined with age, body mass index, and personal and family history, allow the identification of women in the first trimester who are at increased risk of developing GDM.

The impact of regional origin on the incidence of gestational diabetes mellitus in a multiethnic European cohort.

Introduction: Women with migration background present specific challenges related to risk stratification and care of gestational diabetes mellitus (GDM). Therefore, this study aims to investigate the role of ethnic origin on the risk of developing GDM in a multiethnic European cohort. Methods: Pregnant women were included at a median gestational age of 12.9 weeks and assigned to the geographical regions of origin: Caucasian Europe (n = 731), Middle East and North Africa countries (MENA, n = 195), Asia (n = 127) and Sub-Saharan Africa (SSA, n = 48). At the time of recruitment maternal characteristics, glucometabolic parameters and dietary habits were assessed. An oral glucose tolerance test was performed in mid-gestation for GDM diagnosis. Results: Mothers with Caucasian ancestry were older and had higher blood pressure and an adverse lipoprotein profile as compared to non-Caucasian mothers, whereas non-Caucasian women (especially those from MENA countries) had a higher BMI and were more insulin resistant. Moreover, we found distinct dietary habits. Non-Caucasian mothers, especially those from MENA and Asian countries, had increased incidence of GDM as compared to the Caucasian population (OR 1.87, 95%CI 1.40 to 2.52, p < 0.001). Early gestational fasting glucose and insulin sensitivity were consistent risk factors across different ethnic populations, however, pregestational BMI was of particular importance in Asian mothers. Discussion: Prevalence of GDM was higher among women from MENA and Asian countries, who already showed adverse glucometabolic profiles at early gestation. Fasting glucose and early gestational insulin resistance (as well as higher BMI in women from Asia) were identified as important risk factors in Caucasian and non-Caucasian patients.

Hypertensive disorders of pregnancy share common cfDNA methylation profiles.

Hypertensive disorders of pregnancy (HDP) contribute substantially to perinatal morbidity and mortality. Epigenetic changes point towards cardio-metabolic dysregulation for these vascular disorders. In early pregnancy, epigenetic changes using cell free DNA (cfDNA) are largely unexplored. We aimed to investigate these in HDP between 11 and 14 weeks of gestation by analysis of cfDNA methylation profiles in patients with hypertensive disorders. We identified patients without chronic hypertension but with subsequent development of preeclampsia (PE) (n = 11), with chronic hypertension (HT) but without PE development (n = 14), and lacking both PE and HT (n = 422). We matched patients according to PE risk factors into three groups (n = 5 each group): (1) PE: no HT but PE development, (2) HT: chronic hypertension but no PE and (3) Control: no PE or HT. We successfully optimized our cfDNA isolation process prior to whole genome bisulfite sequencing. Analysis of cfDNA methylation changes indicate a common predisposition in PE and HT groups, chiefly of maternal origin. Assessment of significant differentially methylated regions and annotated genes point towards a common cardiovascular predisposition in preeclampsia and hypertension groups in the first trimester. We postulate the pivotal role of the maternal cardiovascular system in HDP, which is already evident in the first trimester.

Gestational diabetes is associated with SARS-CoV-2 infection during pregnancy: A case-control study.

AIM: Individuals with SARS-CoV-2 infection and (pre-existing) diabetes, including pregnant women, present with more severe morbidity, as compared to non-diabetic subjects. To date, evidence is limited concerning the role of gestational diabetes (GDM) in severity of SARS-CoV-2 infection during pregnancy, or vice versa. The aim of our study was to investigate the prevalence of GDM in a SARS-CoV-2 infected pregnant population and evaluate risk factors for and from severe infection in these patients. METHODS: A case-control study with prospective data collection for the case group and 1:2 matching with historical controls based on parity, BMI and ethnicity was conducted (n = 224). GDM screening was performed at 26 weeks' gestation. Multivariate binary logistic regression analysis was performed to assess risk factors for GDM and inpatient COVID-19 management. RESULTS: 34.6% of the patients in the case group suffered from GDM, vs. 16.1% in the control group (p = 0.002). 35.7% patients were diagnosed with GDM after, vs. 33.3% before SARS-CoV-2 infection (OR (95%CI) 1.11(0.40-3.08), p = 0.84), with no correlation between time point of infection and GDM diagnosis. SARS-CoV-2 (OR (95%CI) 2.79 (1.42, 5.47), p = 0.003) and BMI (OR (95%CI) 1.12 (1.05, 1.19), p = 0.001) were significant independent risk factors for GDM. CONCLUSION: Data suggests that GDM increases the risk of infection in SARS-CoV-2 infected pregnant women. Meanwhile, SARS-CoV-2 during pregnancy might increase the risk of developing GDM. Vaccination and caution in using protective measures should be recommended to pregnant women, particularly when suffering from GDM.

Integrating Combined First Trimester Screening for Preeclampsia into Routine Ultrasound Examination.

Introduction The Fetal Medicine Foundation (FMF) London has developed a first trimester screening algorithm for preeclampsia (PE), based on maternal characteristics and past risk factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and placental growth factor (PlGF). The aim of this study was to determine the feasibility of integrating PE screening into routine practice. Material and Methods All pregnancies with a fetal crown-rump length of 45 - 84 mm presenting to our ultrasound department between January 2014 and September 2020 were included in this analysis. Screening for PE was offered to singleton pregnancies only. The number of screening tests performed in the eligible population was assessed and the reasons for missed screenings identified with the help of the electronic clinical database. SPSS Statistics 25 and GraphPad version 8.0 for Windows were used for statistical analysis. Results 6535 pregnancies were included, 4510 (69.0%) of which were screened for PE. The percentage of patients being offered PE screening increased over the years from 63.1 to 96.7% (r s = 0.96; p = 0.003), while the rate of screenings performed in eligible patients remained stable at a median [range] of 86.2% [78.0 - 91.8%] (p = ns). 2025 (31.0%) pregnancies were not screened for PE, 1306 (64.5%) because they were not eligible for screening. 145 (2.2%) women explicitly declined PE screening; their background risk was lower than that of women who accepted screening. Conclusion Our study shows that integration of PE screening into the routine first trimester ultrasound scan is feasible and widely accepted by pregnant women and health care providers.

Perinatal outcomes in singletons after fresh IVF/ICSI: results of two cohorts and the birth registry.

RESEARCH QUESTION: How are perinatal outcomes of live-born singletons after stimulated and unstimulated IVF different from perinatal outcomes in (i) children born in a tertiary centre and (ii) all children born in Switzerland? METHODS: This cohort study compared the perinatal outcomes of two birth cohorts and the national live birth registry. Relative risks were calculated using modified Poisson regression and clustering for siblings and adjustment for maternal age, parity and childs sex. RESULTS: Of the 636,639 live births, 311 were in the Bern IVF Cohort (144 stimulated, 167 unstimulated), 2332 in the tertiary centre and 633,996 in the Swiss Live Birth Registry (SLBR). Perinatal outcomes following IVF did not differ compared with births in the SLBR (adjusted relative risk [aRR]; 95% confidence interval [CI]), with the exception of the increased risk of small for gestational age (1.31; 1.01 to 1.70, P = 0.04; aRR 1.12; 0.87 to 1.45, P = 0.39). Children born following stimulated IVF had a higher risk of low birthweight (2.17; 1.27 to 3.69, P < 0.01; aRR 1.72; 1.01 to 2.93, P = 0.05), and of being small for gestational age (1.50; 1.05 to 2.14, P = 0.03; aRR 1.31; 0.92 to 1.87; P = 0.13), whereas children born after unstimulated IVF had no increased risks compared with the SLBR. Higher Caesarean rate after IVF was mainly associated with higher maternal age. CONCLUSION: Singletons in the Bern IVF Cohort do not show less favourable perinatal outcomes. Gonadotrophin stimulation seems to have an effect, because lower risks were associated with unstimulated IVF.

Is computerized cardiotocography useful in monochorionic twins with selective intrauterine growth restriction?

OBJECTIVE: To assess the value of using computerized cardiotocography (cCTG) short-term variation (STV) for intrapartum monitoring in monochorionic twins (MC) complicated by selective intrauterine growth restriction (sIUGR). MATERIAL AND METHODS: All available cCTGs retrieved from computerized medical records of MC with sIUGR were retrospectively studied regarding the behavior of the STV. sIUGR was defined as intertwin estimated fetal weight (EFW) discordance of ≥20% with the abdominal circumference (AC) below the fifth percentile and/or the EFW of the smaller twin below the 10th percentile. The sIUGR classification system proposed by Gratacos et al. was used using types I-III on the basis of umbilical artery Doppler characteristics of the IUGR twin. The admission (entry) STV and final pre-delivery (last) STV values were analyzed. Cases with intrauterine demise, with structural or chromosomal abnormalities, with twin anemia polycythemia sequence (TAPS) and/or twin-to-twin transfusion syndrome (TTTS) were excluded. RESULTS: During the study period, 64 consecutive cases were managed within our department. Thirty-two cases fulfilled the inclusion criteria for analysis. Mean gestational age at assessment and at delivery was 28.4 ± 2.7 and 31.5 ± 2.2 weeks, respectively. The entry STV and last STV before delivery were not statistically different (mean IUGR STV entry: 9.3 ± 3.4 ms versus last 8 ± 2.2 ms; p = .051; mean co-twin STV entry: 9.1 ± 2.8 ms versus last 9.2 ± 3 ms; p = .87). Neither was the sIUGR-type adjusted STV. CONCLUSIONS: In MC pregnancies complicated by sIUGR, the cCTG STV does not distinguish between fetuses, nor does it show differences in cases of fetal deterioration monitored by conventional CTG.

Differential Diagnosis and Prognosis of Fetuses with Bilateral Enlarged, Hyperechogenic Kidneys: Renal Volume and Amniotic Fluid Volume with Advancing Gestation.

INTRODUCTION: This study's objective was to identify prenatal criteria helping differential diagnosis of bilateral enlarged, hyperechogenic kidneys, especially looking at development of renal volume and amniotic fluid volume with increasing gestational age. METHOD: Retrospective analysis (single-center database) of all bilateral enlarged, hyperechogenic kidneys between 2000-2018. Renal enlargement was defined as renal volume>90th percentile. Evaluation included development of renal and amniotic fluid volume during pregnancy and fetal outcome. RESULTS: 23 cases fulfilled the inclusion criteria. 12 pregnancies were terminated. For 11 continued pregnancies, longitudinal information on amniotic fluid volume and renal volume were available. 4 cases with oligohydramnios showed a progressive reduction; 6 cases with normal/increased amniotic fluid volume remained stable; in 1 case amniotic fluid volume normalized from initially being oligohydramnios. Regarding renal volume, 4 cases showed exponential enlargement, 3 cases linear progression; in 2 cases renal volume stabilized after initial progression; 2 cases showed initial progression and secondary regression. 4 fetuses survived: 3 autosomal dominant polycystic kidney diseases, 1 Bardet-Biedl syndrome. CONCLUSION: Progressive reduction of amniotic fluid volume with exponential increase of renal volume is highly suggestive for autosomal recessive polycystic kidney disease. Cases of autosomal dominant polycystic kidney disease show a linear progression of renal volume>90th percentile and mostly normal amniotic fluid volume.

Reducing the Risk of Preterm Preeclampsia: Comparison of Two First Trimester Screening and Treatment Strategies in a Single Centre in Switzerland.

Introduction First trimester screening for preeclampsia (PE) is based on the combined risks model. Recent trials demonstrate that variations in multiple of the medians (MoMs) of the screening markers influence the performance of the algorithm in different populations. The aim of this study is to compare the performance of the algorithm in two cohorts with different prevention strategies. Material and Methods All first trimester screening tests performed between January 2014 and April 2020 were included. Up to June 2017 pregnancies with a risk > 1 : 200 for early-onset PE (eoPE) were considered at risk and received 100 mg of aspirin (strategy A). From July 2017 onwards, pregnancies with a risk > 1 : 100 for preterm PE (pPE) received 150 mg of aspirin (strategy B). We compared the screen positive rates (SPR) and incidence of PE between the two screening approaches. Statistical analysis were performed with Graphpad 8.0. Results 3552 pregnancies were included; 1577 pregnancies were screened according to strategy A, 1975 pregnancies according to strategy B. The screen positive rate (SPR) for strategy A and B was 8.9 and 16.9% respectively (p < 0.0001) while the incidence of PE was 1.41 and 1.84% respectively (p = ns). Conclusion With a SPR of less than 10% we achieved a remarkably low rate of PE in our population, no further reduction in PE could be achieved by an increase in the SPR and LDA-prescription during the second screening period. The cut-off to define a pregnancy at risk for PE should be tailored to keep the SPR below 10% to avoid unnecessary treatment with aspirin.

Soluble fms-like tyrosine kinase 1 (sFlt-1): A novel biochemical marker for acute fatty liver of pregnancy.

INTRODUCTION: Acute fatty liver of pregnancy (AFLP) substantially contributes to maternal and neonatal morbidity and mortality. Other liver-associated pregnancy complications such as preeclampsia-associated HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome may be difficult to differentiate from AFLP as these diseases overlap with regard to multiple clinical and laboratory features. The aim of this study was to investigate angiogenic profiles by measuring soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in pregnancies compromised by AFLP and to compare them with those complicated by HELLP syndrome. MATERIAL AND METHODS: Pregnant women affected by AFLP or HELLP syndrome were enrolled. The study population of women with HELLP syndrome was part of a larger data collection obtained in our clinic that has been used for previous work. Patients' angiogenic profiles were assessed by measuring sFlt-1 and PlGF serum levels. To assess the diagnostic potential of these angiogenic markers in AFLP, as well as discriminating it from HELLP syndrome, non-parametric tests were used and receiver operating curves were calculated. RESULTS: Six women with AFLP and 48 women with HELLP syndrome were included in the study. Patients with AFLP showed significantly higher sFlt-1 levels (median: 57 570 pg/mL; range 31 609-147 170 pg/mL) than patients with HELLP syndrome (9713 pg/mL; 1348-30 781 pg/mL; p < 0.001). PlGF serum levels were higher in patients with AFLP compared with those with HELLP syndrome (197 pg/mL; 127-487 pg/mL vs. 40 pg/mL; 9-644 pg/mL, respectively; p < 0.01). sFlt-1/PlGF ratios were not significantly different between AFLP and HELLP syndrome patients (192; 157-1159 vs. 232; 3-948, respectively; NS). In our study population, an sFlt-1 cut-off value of 31 100 pg/mL allowed differentiation between these two diseases with a sensitivity and specificity of 100%. A linear correlation was found between the cumulative numbers of Swansea criteria and sFlt-1 serum levels (r = 0.97; p < 0.01). CONCLUSIONS: AFLP is associated with very high sFlt-1 serum levels in particular in women fulfilling eight or more Swansea criteria. Besides the suggested Swansea criteria to diagnose AFLP, an sFlt-1 value above 31 100 pg/mL may be an additional biochemical feature improving discrimination between AFLP and HELLP syndrome. However, because of the small number of pregnancies affected by AFLP included in this work further studies are needed to corroborate our findings.

Double inferior vena cava in a monochorionic twin pregnancy with selective fetal growth restriction.

Congenital anomalies of the infrarenal inferior vena cava (IVC) are well described in adult life, however, little information exists on their associations in fetal life. Here, we describe a case of a monochorionic diamniotic (MCDA) twin pregnancy complicated by selective fetal growth restriction (sFGR) with an incidental finding of a double IVC in one child. In fetal life, variants of the infrarenal IVC are strongly associated with heart defects, which might suggest haemodynamic alterations or genetic causes, even more so in our case with MCDA twins complicated by sFGR.

FIRST TRIMESTER SCREENING FOR PREECLAMPSIA - A SYSTEMATIC REVIEW.

Objective: To increase the detection rate of preterm preeclampsia (PE) first trimester combined screening tests are being developed. The aim of this review is to create an overview of the currently investigated screening markers, algorithms and their validations.Methods: Comprehensive review of the literature concerning first trimester screening for PEResults and conclusions: Studies investigating a total of 160 biochemical, 6 biophysical and 14 ultrasound markers could be identified. Of the 21 algorithms published, mainly the algorithm published by the Fetal Medicine Foundation London has been validated. This algorithm performes significantly better than screening by anamnestic risk factors only.