Case report of a rare cause of secondary hypertension illustrating the importance of cardio-obstetric preconception counselling.

Background: Cardiovascular diseases represent a leading cause of maternal morbidity and mortality in industrialized countries. High blood pressure during pregnancy is a major driver of short- and long-term cardiovascular health in both mother and child. Screening and adequate treatment of elevated blood pressure before pregnancy significantly reduce mortality risk to mother and child. Case summary: A 30-year-old woman with middle aortic coarctation (MAC) previously treated with aortic stenting was referred to our cardio-obstetrics with plans to become pregnant. The clinical examination revealed severe hypertension with a significant blood pressure gradient between the upper and lower limbs. The patient underwent computed tomography angiography showing re-stenosis of the aorta. After the analysis of the benefit risk of all treatment options, percutaneous transluminal aortic in-stent re-stenting was performed. Following the intervention, blood pressure profile significantly improved but remained slightly elevated further necessitating the introduction of an antihypertensive therapy. Discussion: This clinical case condenses several challenges encountered in the management of hypertension in women who plan to become pregnant. Firstly, it emphasizes the fact that secondary causes of chronic hypertension, including MAC, do not have to be overlooked in childbearing age patient. Secondly, it illustrates the need for a multidisciplinary analysis of all available treatment options in view of a future pregnancy. Finally, it discusses the particular follow-up and potential complications in pregnant women with MAC and aortic stent.

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.

Mediating processes underlying the associations between maternal obesity and the likelihood of cesarean birth.

BACKGROUND: Pregnant women with obesity are more likely to experience cesarean birth compared to women without obesity. Yet, little is known about the underlying mechanisms. The objective of this study was therefore to evaluate how mediators contribute to the association between obesity and prelabor/intrapartum cesarean birth. METHODS: We retrospectively analyzed Swiss cohort data from 394,812 singleton, cephalic deliveries between 2005 and 2020. Obesity (BMI ≥ 30 kg/m2 ) was defined as the exposure and prelabor or intrapartum cesarean birth as the outcomes. Hypothesized mediators included gestational comorbidities, large-for-gestational-age infant, pregnancy duration >410/7 weeks, slower labor progress, labor induction, and history of cesarean birth. We performed path analyses using generalized structural equation modeling and assessed mediation by a counterfactual approach. RESULTS: Women with obesity had a cesarean birth rate of 39.36% vs. 24.12% in women without obesity. The path models mainly showed positive direct and indirect associations between obesity and cesarean birth. In the total sample, the mediation models explained up to 39.47% (95% CI 36.92-42.02) of the association between obesity and cesarean birth, and up to 57.13% (95% CI 54.10-60.16) when including history of cesarean birth as mediator in multiparous women. Slower labor progress and history of cesarean birth were found to be the most clinically significant mediators. CONCLUSIONS: This study provides empirical insights into how obesity may increase cesarean birth rates through mediating processes. Particularly allowing for a slower labor progress in women with obesity might reduce cesarean birth rates and prevent subsequent repeat cesarean births in multiparous women.

"Don't add fuel to the fire"- Hyperhemolysis Syndrome in a pregnant woman with compound Sickle cell disease/ß0-thalassemia - Case report and review of the literature.

Hyperhemolysis Syndrome (HHS) is a rare and severe post-transfusion complication characterized by the destruction of both recipient and donor red blood cells (RBC). The underlying mechanism of HHS is not fully understood and proper management can be difficult. Furthermore, there are few reports regarding HHS in pregnancy. We report on the development and management of HHS in a pregnant woman with known compound Sickle cell disease/ß-0-thalassemia after transfusion of not fully compatible packed red blood cells (PRBC). We aim to raise awareness on this diagnostically challenging and life-threatening type of hemolysis with this report, and to stress the need to consider the diagnosis of HHS in SCD patients with progressive anemia despite PRBC administration.

Fetal RHD Screening in RH1 Negative Pregnant Women: Experience in Switzerland.

RH1 incompatibility between mother and fetus can cause hemolytic disease of the fetus and newborn. In Switzerland, fetal RHD genotyping from maternal blood has been recommended from gestational age 18 onwards since the year 2020. This facilitates tailored administration of RH immunoglobulin (RHIG) only to RH1 negative women carrying a RH1 positive fetus. Data from 30 months of noninvasive fetal RHD screening is presented. Cell-free DNA was extracted from 7192 plasma samples using a commercial kit, followed by an in-house qPCR to detect RHD exons 5 and 7, in addition to an amplification control. Valid results were obtained from 7072 samples, with 4515 (64%) fetuses typed RHD positive and 2556 (36%) fetuses being RHD negative. A total of 120 samples led to inconclusive results due to the presence of maternal or fetal RHD variants (46%), followed by women being serologically RH1 positive (37%), and technical issues (17%). One sample was typed false positive, possibly due to contamination. No false negative results were observed. We show that unnecessary administration of RHIG can be avoided for more than one third of RH1 negative pregnant women in Switzerland. This reduces the risks of exposure to a blood-derived product and conserves this limited resource to women in actual need.

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.

Sonographic and Magnetic Resonance Characteristics of Gynecological Sarcoma.

INTRODUCTION: Gynecological sarcomas are rare malignant tumors with an incidence of 1.5-3/100,000 and are 3-9% of all malignant uterine tumors. The preoperative differentiation between sarcoma and myoma becomes increasingly important with the development of minimally invasive treatments for myomas, as this means undertreatment for sarcoma. There are currently no reliable laboratory tests or imaging-characteristics to detect sarcomas. The objective of this article is to gain an overview of sarcoma US/MRI characteristics and assess their accuracy for preoperative diagnosis. METHODS: A systematic literature review was performed and 12 studies on ultrasound and 21 studies on MRI were included. RESULTS: For the ultrasound, these key features were gathered: solid tumor > 8 cm, unsharp borders, heterogeneous echogenicity, no acoustic shadowing, rich vascularization, and cystic changes within. For the MRI, these key features were gathered: irregular borders; heterogeneous; high signal on T2WI intensity; and hemorrhagic and necrotic changes, with central non-enhancement, hyperintensity on DWI, and low values for ADC. CONCLUSIONS: These features are supported by the current literature. In retrospective analyses, the ultrasound did not show a sufficient accuracy for diagnosing sarcoma preoperatively and could also not differentiate between the different subtypes. The MRI showed mixed results: various studies achieved high sensitivities in their analysis, when combining multiple characteristics. Overall, these findings need further verification in prospective studies with larger study populations.

Immunology of pregnancy and reproductive health in autoimmune rheumatic diseases. Update from the 11th International Conference on Reproduction, Pregnancy and Rheumatic Diseases.

Autoimmune rheumatic diseases (ARD) can affect women and men during fertile age, therefore reproductive health is a priority issue in rheumatology. Many topics need to be considered during preconception counselling: fertility, the impact of disease-related factors on pregnancy outcomes, the influence of pregnancy on disease activity, the compatibility of medications with pregnancy and breastfeeding. Risk stratification and individualized treatment approach elaborated by a multidisciplinary team minimize the risk of adverse pregnancy outcomes (APO). Research has been focused on identifying biomarkers that can be predictive of APO. Specifically, preeclampsia and hypertensive disorders of pregnancy tend to develop more frequently in women with ARD. Placental insufficiency can lead to intrauterine growth restriction and small-for-gestational age newborns. Such APO have been shown to be associated with maternal disease activity in different ARD. Therefore, a key message to be addressed to the woman wishing for a pregnancy and to her family is that treatment with compatible drugs is the best way to ensure maternal and fetal wellbeing. An increasing number of medications have entered the management of ARD, but data about their use in pregnancy and lactation are scarce. More information is needed for most biologic drugs and their biosimilars, and for the so-called small molecules, while there is sufficient evidence to recommend the use of TNF inhibitors if needed for keeping maternal disease under control. Other issues related to the reproductive journey have emerged as "unmet needs", such as sexual dysfunction, contraception, medically assisted reproduction techniques, long-term outcome of children, and they will be addressed in this review paper. Collaborative research has been instrumental to reach current knowledge and the future will bring novel insights thanks to pregnancy registries and prospective studies that have been established in several Countries and to their joint efforts in merging data.

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.

Mental health in pregnant individuals during the COVID-19 pandemic based on a Swiss online survey.

The aim of our study was to evaluate the mental health of pregnant individuals during the early COVID-19 pandemic and the potential factors associated. A Swiss online survey was proposed to individuals who gave birth during the pandemic period from March 2020. The Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder 7 questions (GAD-7), and Impact Event Scale-Revised (IES-R) were evaluated and used to defined mental health impairment as a composite outcome. From October, 2020 to February, 2021, 736 participants responded. The anxiety GAD-7 score was moderate in 9.6% and severe in 2.0%. The EPDS was moderate in 21.5% and severe in 32.9%. The IES-R was moderate in 10.3% and severe in 3.9%. Mental health impairment was reported in 37.0%. The association between the risk of mental health impairment and foreign nationality was significant (OR = 1.48; 95%CI [1.06-2.05]) as well as fetal and pregnancy worries because of coronavirus (OR = 1.46; 95% CI [1.08-1.98]) and 1.65; 95% CI [1.22-2.24]). Adjusted ORs were significant for foreign nationality (aOR = 1.51; 95%CI [1.07-2.13]) and pregnancy worries because of coronavirus (aOR = 1.62; 95%CI [1.10-2.40]). Pregnant people and especially foreign national have a high risk of mental health impairment during the pandemic.

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.

Obstetrical and Fertility Outcomes Following Transcatheter Pelvic Arterial Embolization for Postpartum Hemorrhage: A Cohort Follow-Up Study.

Objectives: Management of severe postpartum hemorrhage (PPH) includes transcatheter pelvic arterial embolization (TAE). Data regarding subsequent fertility and obstetrical outcomes is limited, as most fertility outcomes derive from TAE in uterine fibroma. The purpose of our study was to evaluate the long-term outcomes of patients undergoing TAE, particularly concerning subsequent fertility and following pregnancies. Material and methods: We included 28 patients who underwent TAE for PPH at our institution between 2009 and 2018 in a retrospective cohort study. Data were assessed by reviewing patients' charts and by contacting the patients. Results: Ten patients had prophylactic balloon occlusion before cesarean section because of anticipated PPH, with planned hysterectomy by placenta increta/percreta. All these patients were excluded from the analysis regarding fertility. 16 (73%) patients reported having regular menstruation after TAE. In total, 11 women had no desire for subsequent pregnancy. Seven of the remaining 11 patients (63.6%) had a total of 13 spontaneous pregnancies, nine of these resulted in miscarriages. Four patients delivered a live baby (36.4%). Two of these (50%) had recurrent PPH and treatment was conservative. Of the patients with infertility (n = 4, 36.4%), two (18.1%) underwent assisted infertility treatment without success. Conclusion: Our study suggests that the fertility of patients undergoing TAE due to PPH is limited. In women who conceive, the risk for first trimester miscarriage as well as recurrent PPH seems to be increased. If this is a consequence of the underlying cause of PPH or the TAE remains unknown. Larger follow-up cohorts are needed. In the meantime, patients who desire pregnancy after TAE should be counseled accordingly.

Low Birth Weight and Impaired Later Lung Function: Results from a Monochorionic Twin Study.

Rationale: Fetal growth restriction (FGR) and resulting low birth weight are risk factors for impaired lung development. However, both are often correlated with other factors, especially prematurity. Therefore, the question whether lung function changes in individuals with FGR are driven by gestational age, fetal growth, or both often remains unanswered. Objectives: To examine the association of birth weight with lung function in monochorionic twins with selective FGR in one twin. Methods: We included 20 monochorionic twin pairs with selective FGR and subsequent discordant birth weight with a minimum age of 6 years. In this unique case-control design, the smaller twin represents the case and the cotwin the almost identical counterpart. They performed spirometry and underwent body plethysmography, multiple-breath washout, and magnetic resonance imaging (MRI). We compared lung function and MRI outcomes between the smaller twins and their cotwins by paired t tests, and we used mixed linear models to assess the association between birth weight and outcomes. Results: Mean study age was 18.4 years (range, 7.5-29.4), and mean difference in birth weight within the twin pairs was 575 g (range, 270-1,130). The mean difference of forced expiratory volume in 1 second z-score was -0.64 (95% confidence interval [CI], -0.98 to -0.30), and -0.55 (95% CI, -0.92 to -0.18) of forced vital capacity z-score between the smaller twins and their cotwins. Both were associated with birth weight: per 500 g of birth weight, forced expiratory volume in 1 second z-score increased by 0.50 (95% CI, 0.35-0.65; P < 0.001) and forced vital capacity z-score increased by 0.44 (95% CI, 0.31-0.57; P < 0.001). Sacin from multiple-breath washout, as a marker for ventilation inhomogeneity of acinar airways, was elevated in the smaller twins and was associated with low birth weight. There was no difference for MRI outcomes. The results remained similar after adjustment for study height. Conclusions: Low birth weight was associated with reduced large and small airway function independent of gestational age and body growth. Our findings suggest that intrauterine impairment of lung development induced by FGR has significant consequences on lung function until early adulthood.

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.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

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.