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STUDY QUESTION Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles? SUMMARY ANSWER Using the utero-placental vascular skeleton (uPVS) as a new imaging marker, this study reveals morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic growth and development, fetal growth, and birth weight percentiles. WHAT IS KNOWN ALREADY First-trimester development of the utero-placental vasculature is associated with placental function, which subsequently impacts embryonic and fetal ability to reach their full growth potential. The attribution of morphologic variations in the utero-placental vascular development, including the vascular structure and branching density, on prenatal growth remains unknown. STUDY DESIGN, SIZE, DURATION This study was conducted in the VIRTUAL Placental study, a subcohort of 214 ongoing pregnancies, embedded in the prospective observational Rotterdam Periconception Cohort (Predict study). Women were included before 10 weeks gestational age (GA) at a tertiary referral hospital in The Netherlands between January 2017 and March 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS We obtained three-dimensional power Doppler volumes of the gestational sac including the embryo and the placenta at 7, 9, and 11 weeks of gestation. Virtual Reality-based segmentation and a recently developed skeletonization algorithm were applied to the power Doppler volumes to generate the uPVS and to measure utero-placental vascular volume (uPVV). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-crossing-, or vessel point). Additionally, total vascular length (mm) was calculated. The ratios of the uPVS characteristics to the uPVV were calculated to determine the density of vascular branching. Embryonic growth was estimated by crown-rump length and embryonic volume. Embryonic development was estimated by Carnegie stages. Fetal growth was measured by estimated fetal weight in the second and third trimester and birth weight percentiles. Linear mixed models were used to estimate trajectories of longitudinal measurements. Linear regression analysis with adjustments for confounders was used to evaluate associations between trajectories of the uPVS and prenatal growth. Groups were stratified for conception method (natural/IVF-ICSI conceptions), fetal sex (male/female), and the occurrence of placenta-related complications (yes/no). MAIN RESULTS AND THE ROLE OF CHANCE Increased absolute vascular morphologic development, estimated by positive random intercepts of the uPVS characteristics, is associated with increased embryonic growth, reflected by crown-rump length (endpoints β  = 0.017, 95% CI [0.009; 0.025], bifurcation points β  = 0.012, 95% CI [0.006; 0.018], crossing points β  = 0.017, 95% CI [0.008; 0.025], vessel points β  = 0.01, 95% CI [0.002; 0.008], and total vascular length β  = 0.007, 95% CI [0.003; 0.010], and similarly with embryonic volume and Carnegie stage, all P -values ≤ 0.01. Density of vascular branching was negatively associated with estimated fetal weight in the third trimester (endpoints: uPVV β = −94.972, 95% CI [−185.245; −3.698], bifurcation points: uPVV β = −192.601 95% CI [−360.532; −24.670]) and birth weight percentiles (endpoints: uPVV β = −20.727, 95% CI [−32.771; −8.683], bifurcation points: uPVV β −51.097 95% CI [−72.257; −29.937], and crossing points: uPVV β = −48.604 95% CI [−74.246; −22.961])), all P -values < 0.05. After stratification, the associations were observed in natural conceptions specifically. LIMITATION, REASONS FOR CAUTION Although the results of this prospective observational study clearly demonstrate associations between first-trimester utero-placental vascular morphologic development and prenatal growth, further research is required before we can draw firm conclusions about a causal relationship. WIDER IMPLICATIONS OF THE FINDINGS Our findings support the hypothesis that morphologic variations in utero-placental vascular development play a role in the vascular mechanisms involved in embryonic and fetal growth and development. Application of the uPVS could benefit our understanding of the pathophysiology underlying placenta-related complications. Future research should focus on the clinical applicability of the uPVS as an imaging marker for the early detection of fetal growth restriction. STUDY FUNDING/COMPETING INTEREST(S) This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest. TRIAL REGISTRATION NUMBER Registered at the Dutch Trial Register (NTR6854). [ABSTRACT FROM AUTHOR]

Objectives: Fetal growth restriction (FGR) is a condition characterized by its complexity in diagnosis and management. There is a need for early accurate diagnosis, evidence-based monitoring and management of FGR to improve neonatal outcomes. This study evaluated differences and similarities in protocols of Dutch hospitals in the approach of (suspected) FGR in the context of the national guideline.Study Design: FGR protocols were collected from Dutch hospitals between November 2019 and June 2020. Collected data were coded for further analysis and categorized in eight predetermined key domains of definition, preventive measures, testing, referral, monitoring strategies, interventions, mode of delivery and pathologic placenta examination.Results: 55 of 71 approached hospitals (78 %) responded to the request and 54 protocols (76 %) were obtained. Protocols used variable definitions of FGR, and management was mostly based on fetal biometry results in combination with Doppler results (n = 47, 87 %). In pregnancies with an abdominal circumference (AC) or an estimated fetal weight (EFW) <10th percentile with normal Doppler results, induction of labour was recommended ≥37 weeks (n = 1, 2 %), ≥38-40 weeks (n = 23, 43 %); ≥41 weeks (n = 1, 2 %) or not specified (n = 29, 54 %). In case of an umbilical artery (UA) Doppler pulsatility index >95th percentile, (preterm) labour induction was recommended in the majority of the protocols regardless of fetal size (≥36 weeks: n = 2, 4 %; ≥37 weeks: n = 41, 76 %, not stated: n = 11, 20 %).Conclusion: This study found practice variation in all predetermined domains of FGR protocols of Dutch hospitals, underscoring the complexity of the condition. The differences found in this study feed the research agenda that informs the process of improving obstetric care by better identification of the fetus at risk for consequences of FGR, improving evidence-based monitoring strategies to identify (imminent) fetal hypoxia, and more accurate timing of delivery. [ABSTRACT FROM AUTHOR]

Objectives: First, assess accuracy of late third trimester universal fetal growth screening in high risk nulliparous women with a singleton in vertex presentation at term. Second, assess instrumental delivery rates and perinatal outcomes in this population.Study Design: Single centre retrospective cohort study in a teaching hospital, The Netherlands.Results: In a cohort of 1902 pregnancies, growth ultrasound after 33 weeks was moderately accurate in detecting children with a birthweight below the 10th centile with a sensitivity of 46.2% and a false positive rate of 4.7%. Induction of labour followed an antenatal suspicion of FGR more often than in the group with normal expected fetal weight (73.4% vs 52.6% OR 2.49 (1.88-3.3)) as could be expected from application of guidelines. The caesarean section rates was lowest in the group with suspected FGR compared to the group with expected normal fetal weight (15.2% vs 22.1% OR 0.63 (0.45-0.9)). There were no differences between both groups in rates of composite severe adverse perinatal outcome (0.7% vs 0.8% OR 0.87 (0.2-3.93)).Conclusions: The detection of growth restriction using universal screening in term high risk nulliparous women with a singleton in vertex position is moderate. Despite this, caesarean section rates were not increased and perinatal outcomes were similar when compared to that found in the randomized controlled trial on which the recommendation for induction of labour for suspected term FGR is based. This supports universal late third trimester fetal growth screening in pregnancies under consultant-led care in the two tiers Dutch obstetrical system. [ABSTRACT FROM AUTHOR]

Objective: To identify neonatal risk for severe adverse perinatal outcomes across birth weight centiles in two Dutch and one international birth weight chart.Background: Growth restricted newborns have not reached their intrinsic growth potential in utero and are at risk of perinatal morbidity and mortality. There is no golden standard for the confirmation of the diagnosis of fetal growth restriction after birth. Estimated fetal weight and birth weight below the 10th percentile are generally used as proxy for growth restriction. The choice of birth weight chart influences the specific cut-off by which birth weight is defined as abnormal, thereby triggering clinical management. Ideally, this cut-off should discriminate appropriately between newborns at low and at high risk of severe adverse perinatal outcomes and consequently correctly inform clinical management.Methods: This is a secondary analysis of the IUGR Risk Selection (IRIS) study. Newborns (n = 12 953) of women with a low-risk status at the start of pregnancy and that received primary antenatal care in the Netherlands were included. We examined the distribution of severe adverse perinatal outcomes across birth weight centiles for three birth weight charts (Visser, Hoftiezer and INTERGROWTH) by categorizing birth weight centile groups and comparing the prognostic performance for severe adverse perinatal outcomes. Severe adverse perinatal outcomes were defined as a composite of one or more of the following: perinatal death, Apgar score < 4 at 5 min, impaired consciousness, asphyxia, seizures, assisted ventilation, septicemia, meningitis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis.Results: We found the highest rates of severe adverse perinatal outcomes among the smallest newborns (< 3rd percentile) (6.2% for the Visser reference curve, 8.6% for the Hoftiezer chart and 12.0% for the INTERGROWTH chart). Discriminative abilities of the three birth weight charts across the entire range of birth weight centiles were poor with areas under the curve ranging from 0.57 to 0.61. Sensitivity rates of the various cut-offs were also low.Conclusions: The clinical utility of all three charts in identifying high risk of severe adverse perinatal outcomes is poor. There is no single cut-off that discriminates clearly between newborns at low or high risk.Trial Registration: Netherlands Trial Register NTR4367 . Registration date March 20th, 2014. [ABSTRACT FROM AUTHOR]

Background: Unfavorable lipid profile is associated with pregnancy disorders characterized by uteroplacental dysfunction, including hypertensive disorders of pregnancy, preterm birth and fetal growth restriction. None of current tools used to predict the risk of pregnancy complications include lipid levels., Objective(s): In this study, we examined the association of preconception lipid profile with pregnancy disorders characterized by uteroplacental dysfunction in a multi-ethnic population, aiming to improve the identification of women at high risk for uteroplacental dysfunction using current prediction models., Study Design: We conducted a linkage study combining lipid profile collected in the multi-ethnic HELIUS study (Amsterdam, 2011-2015), linked with national perinatal registry data on pregnancy complications after inclusion until 2019. We included 1177 women of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan origin. Associations were studied using Poisson regression. The discriminative ability was assessed for different pregnancy complications of significantly associated lipid parameters when added to commonly used prediction tools for preeclampsia., Results: Preconception triglyceride level was associated with prevalence of hypertensive disorders of pregnancy (e^triglyceride level (mmol/L) adjusted prevalence ratio 1.07, 95% CI 1.00 to 1.14). Age-adjusted prevalence of hypertensive disorders of pregnancy was also higher among women with high LDL-C level, high TC/HDL-C or ≥4 adverse lipid parameters, but most of these findings were not statistically significant when adjusted for demographic, lifestyle and medical characteristics. Addition of triglyceride level and other lipid parameters to the NICE guideline criteria and to the EXPECT prediction tool did not improve discriminative ability for hypertensive disorders of pregnancy, preterm birth or fetal growth restriction., Conclusion(s): Lipid profile did not aid in the identification of women at high risk for pregnancy disorders characterized by uteroplacental dysfunction. Further studies are needed to improve preconception prediction models for hypertensive disorders of pregnancy and other pregnancy disorders characterized by uteroplacental dysfunction using biomarkers or other easily available measurements., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Study Question: Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles?, Summary Answer: Using the utero-placental vascular skeleton (uPVS) as a new imaging marker, this study reveals morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic growth and development, fetal growth, and birth weight percentiles., What Is Known Already: First-trimester development of the utero-placental vasculature is associated with placental function, which subsequently impacts embryonic and fetal ability to reach their full growth potential. The attribution of morphologic variations in the utero-placental vascular development, including the vascular structure and branching density, on prenatal growth remains unknown., Study Design, Size, Duration: This study was conducted in the VIRTUAL Placental study, a subcohort of 214 ongoing pregnancies, embedded in the prospective observational Rotterdam Periconception Cohort (Predict study). Women were included before 10 weeks gestational age (GA) at a tertiary referral hospital in The Netherlands between January 2017 and March 2018., Participants/materials, Setting, Methods: We obtained three-dimensional power Doppler volumes of the gestational sac including the embryo and the placenta at 7, 9, and 11 weeks of gestation. Virtual Reality-based segmentation and a recently developed skeletonization algorithm were applied to the power Doppler volumes to generate the uPVS and to measure utero-placental vascular volume (uPVV). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-crossing-, or vessel point). Additionally, total vascular length (mm) was calculated. The ratios of the uPVS characteristics to the uPVV were calculated to determine the density of vascular branching. Embryonic growth was estimated by crown-rump length and embryonic volume. Embryonic development was estimated by Carnegie stages. Fetal growth was measured by estimated fetal weight in the second and third trimester and birth weight percentiles. Linear mixed models were used to estimate trajectories of longitudinal measurements. Linear regression analysis with adjustments for confounders was used to evaluate associations between trajectories of the uPVS and prenatal growth. Groups were stratified for conception method (natural/IVF-ICSI conceptions), fetal sex (male/female), and the occurrence of placenta-related complications (yes/no)., Main Results and the Role of Chance: Increased absolute vascular morphologic development, estimated by positive random intercepts of the uPVS characteristics, is associated with increased embryonic growth, reflected by crown-rump length (endpoints β = 0.017, 95% CI [0.009; 0.025], bifurcation points β = 0.012, 95% CI [0.006; 0.018], crossing points β = 0.017, 95% CI [0.008; 0.025], vessel points β = 0.01, 95% CI [0.002; 0.008], and total vascular length β = 0.007, 95% CI [0.003; 0.010], and similarly with embryonic volume and Carnegie stage, all P-values ≤ 0.01. Density of vascular branching was negatively associated with estimated fetal weight in the third trimester (endpoints: uPVV β = -94.972, 95% CI [-185.245; -3.698], bifurcation points: uPVV β = -192.601 95% CI [-360.532; -24.670]) and birth weight percentiles (endpoints: uPVV β = -20.727, 95% CI [-32.771; -8.683], bifurcation points: uPVV β -51.097 95% CI [-72.257; -29.937], and crossing points: uPVV β = -48.604 95% CI [-74.246; -22.961])), all P-values < 0.05. After stratification, the associations were observed in natural conceptions specifically., Limitation, Reasons for Caution: Although the results of this prospective observational study clearly demonstrate associations between first-trimester utero-placental vascular morphologic development and prenatal growth, further research is required before we can draw firm conclusions about a causal relationship., Wider Implications of the Findings: Our findings support the hypothesis that morphologic variations in utero-placental vascular development play a role in the vascular mechanisms involved in embryonic and fetal growth and development. Application of the uPVS could benefit our understanding of the pathophysiology underlying placenta-related complications. Future research should focus on the clinical applicability of the uPVS as an imaging marker for the early detection of fetal growth restriction., Study Funding/competing Interest(s): This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest., Trial Registration Number: Registered at the Dutch Trial Register (NTR6854)., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Screening for, diagnosis and management of intrauterine growth restriction (IUGR) is often performed in multidisciplinary collaboration. However, variation in screening methods, diagnosis and management of IUGR may lead to confusion. In the Netherlands two monodisciplinary guidelines on IUGR do not fully align. To facilitate effective collaboration between different professionals in perinatal care, we undertook a Delphi study with uniform recommendations as our primary result, focusing on issues that are not aligned or for which specifications are lacking in the current guidelines.Methods: We conducted a Delphi study in three rounds. A purposively sampled selection of 56 panellists participated: 27 representing midwife-led care and 29 obstetrician-led care. Consensus was defined as agreement between the professional groups on the same answer and among at least 70% of the panellists within groups.Results: Per round 51 or 52 (91% - 93%) panellists responded. This has led to consensus on 27 issues, leading to four consensus based recommendations on screening for IUGR in midwife-led care and eight consensus based recommendations on diagnosis and eight on management in obstetrician-led care. The multidisciplinary project group decided on four additional recommendations as no consensus was reached by the panel. No recommendations could be made about induction of labour versus expectant monitoring, nor about the choice for a primary caesarean section.Conclusions: We reached consensus on recommendations for care for IUGR within a multidisciplinary panel. These will be implemented in a study on the effectiveness and cost-effectiveness of routine third trimester ultrasound for monitoring fetal growth. Research is needed to evaluate the effects of implementation of these recommendations on perinatal outcomes.Trial Registration: NTR4367 . [ABSTRACT FROM AUTHOR]

Objective: In the TRUFFLE (Trial of Randomized Umbilical and Fetal Flow in Europe) study on the outcome of early fetal growth restriction, women were allocated to one of three groups of indication for delivery according to the following monitoring strategies: (1) reduced fetal heart rate (FHR) short-term variation (STV) on cardiotocography (CTG); (2) early changes in fetal ductus venosus (DV) waveform (DV-p95); and (3) late changes in fetal DV waveform (DV-no-A). However, many infants per monitoring protocol were delivered because of safety-net criteria, for maternal or other fetal indications, or after 32 weeks of gestation when the protocol was no longer applied. The objective of the present posthoc subanalysis was to investigate the indications for delivery in relation to 2-year outcome in infants delivered before 32 weeks to further refine management proposals.Methods: We included all 310 cases of the TRUFFLE study with known outcome at 2 years' corrected age and seven fetal deaths, excluding seven cases with inevitable perinatal death. Data were analyzed according to the allocated fetal monitoring strategy in combination with the indication for delivery.Results: Overall, only 32% of liveborn infants were delivered according to the specified monitoring parameter for indication for delivery; 38% were delivered because of safety-net criteria, 15% for other fetal reasons and 15% for maternal reasons. In the CTG-STV group, 51% of infants were delivered because of reduced STV. In the DV-p95 group, 34% of infants were delivered because of abnormal DV and, in the DV-no-A group, only 10% of infants were delivered accordingly. The majority of infants in the DV groups were delivered for the safety-net criterion of spontaneous decelerations in FHR. Two-year intact survival was highest in the DV groups combined compared with the CTG-STV group (P = 0.05 for live births only, P = 0.21 including fetal death), with no difference between DV groups. A poorer outcome in the CTG-STV group was restricted to infants delivered because of FHR decelerations in the safety-net subgroup. Infants delivered because of maternal reasons had the highest birth weight and a non-significantly higher intact survival.Conclusions: In this subanalysis of infants delivered before 32 weeks, the majority were delivered for reasons other than the allocated monitoring strategy indication. Since, in the DV group, CTG-STV criteria were used as a safety net but in the CTG-STV group, no DV safety-net criteria were applied, we speculate that the slightly poorer outcome in the CTG-STV group might be explained by the absence of DV data. The optimal timing of delivery of fetuses with early intrauterine growth restriction may therefore be best determined by monitoring them longitudinally, with both DV and CTG monitoring. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess the underlying risk factors for perinatal mortality in term born small for gestational age infants.Study Design: We performed a population based nationwide cohort study in the Netherlands of 465,532 term born infants from January 2010 to January 2013. Logistic regression analyses were performed. Also audit results were studied for detailed care information.Results: We studied 162 small for gestational age infants who died in the perinatal period. Risk factors were: gestational age at 37completed weeks (adjusted Odds Ratio (aOR) 2.6, 95% Confidence Interval (CI) 1.6-4.3), male gender (aOR 1.4, 95% CI 1.01-1.9), South Asian ethnicity (aOR 3.6, 95% CI 1.6-8.4), African (aOR 3.5, 95% CI 1.9-6.5) and other non-Western ethnicity (aOR 1.9, CI 1.2-3.1). At 37 completed weeks gestation audit results showed that 26% of the women smoked, 91% were boys and in all but one case death occurred before birth. In 61% of all deceased SGA infants born at 37 completed weeks gestation referral from primary care by independent midwives to the obstetrician took place because of antepartum death before labor.Conclusions: Gestational age of 37 completed weeks, male gender, South Asian, African or other non-Western ethnicity and smoking are associated with perinatal mortality in SGA infants. These risk factors concern the complete term population starting at 37 weeks or even earlier. Therefore, it is of utmost importance to develop accurate diagnostic tests to screen for SGA before 36 weeks gestation to prevent perinatal mortality at term in SGA infants. [ABSTRACT FROM AUTHOR]

Objective: To study the prevalence of metabolic syndrome in women after a pregnancy complicated by pre-eclampsia or small-for-gestational-age (SGA), both epitomes of placental syndrome.Design: A retrospective cohort study.Setting: Single tertiary centre for maternal medicine in the Netherlands.Population: Women with a history of pre-eclampsia in absence of SGA (n = 742) or pregnancy complicated by normotensive SGA (n = 147) between 1996 and 2010.Methods: Women were routinely screened for underlying cardiometabolic and cardiovascular risk factors at least 6 months postpartum. Logistic regression analysis was used to calculate the odds ratio and adjusted odds ratio for each group. Adjustments were made for age, maternal height, smoking, parity, and interval between delivery and measurement.Main Outcome Measures: Prevalence of the metabolic syndrome.Results: The prevalence of the metabolic syndrome in our population was two-fold higher for women with a history of pre-eclampsia (13.9%) compared with women with a history of SGA (7.6%). Calculated odds ratios for metabolic syndrome, fasting insulin, HOMA, and microalbuminuria were all higher for women with a history of pre-eclampsia compared with women with SGA. This difference persisted after adjustment for confounding factors: metabolic syndrome (adjusted odds ratio, aOR 2.11; 95% confidence interval, 95% CI 1.00-4.47) and hyperinsulinaemia (aOR 1.78; 95% CI 1.13-2.81) insulin resistance (HOMAIR ; aOR 1.80; 95% CI 1.14-2.86). Microalbuminuria (aOR 1.58; 95% CI 0.85-2.93) did not reach the level of significance after adjustment for confounding factors.Conclusions: A history of pre-eclampsia, rather than SGA, was associated with metabolic syndrome, suggesting that it relates to maternal rather than fetal etiology of placental syndrome. [ABSTRACT FROM AUTHOR]

The STRIDER is an international consortium of five randomised trials of the use of sildenafil to treat fetal growth restriction. We describe the scientific rationale and processes undertaken to take advantage of such a joint approach to studying new interventions in pregnancy. We also describe the challenges faced during recruitment and the further challenges faced after initial publication. We discuss concerns about fetal wellbeing identified in the Netherlands STRIDER trial and the implications of this on other studies and the wider maternity research community. [ABSTRACT FROM AUTHOR]

Background: Worldwide, hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR) and preterm birth remain the leading causes of maternal and fetal pregnancy-related mortality and (long-term) morbidity. Fetal cardiac deformation changes can be the first sign of placental dysfunction, which is associated with HDP, FGR and preterm birth. In addition, preterm birth is likely associated with changes in electrical activity across the uterine muscle. Therefore, fetal cardiac function and uterine activity can be used for the early detection of these complications in pregnancy. Fetal cardiac function and uterine activity can be assessed by two-dimensional speckle-tracking echocardiography (2D-STE), non-invasive fetal electrocardiography (NI-fECG), and electrohysterography (EHG). This study aims to generate reference values for 2D-STE, NI-fECG and EHG parameters during the second trimester of pregnancy and to investigate the diagnostic potential of these parameters in the early detection of HDP, FGR and preterm birth., Methods: In this longitudinal prospective cohort study, eligible women will be recruited from a tertiary care hospital and a primary midwifery practice. In total, 594 initially healthy pregnant women with an uncomplicated singleton pregnancy will be included. Recordings of NI-fECG and EHG will be made weekly from 22 until 28 weeks of gestation and 2D-STE measurements will be performed 4-weekly at 16, 20, 24 and 28 weeks gestational age. Retrospectively, pregnancies complicated with pregnancy-related diseases will be excluded from the cohort. Reference values for 2D-STE, NI-fECG and EHG parameters will be assessed in uncomplicated pregnancies. After, 2D-STE, NI-fCG and EHG parameters measured during gestation in complicated pregnancies will be compared with these reference values., Discussion: This will be the a large prospective study investigating new technologies that could potentially have a high impact on antepartum fetal monitoring., Trial Registration: Registered on 26 March 2020 in the Dutch Trial Register (NL8769) via https://www.trialregister.nl/trials and registered on 21 October 2020 to the Central Committee on Research Involving Human Subjects (NL73607.015.20) via https://www.toetsingonline.nl/to/ccmo&#95;search.nsf/Searchform?OpenForm ., (© 2021. The Author(s).)

Objective: To assess the value of computerized cardiotocography (cCTG) with calculation of fetal heart rate (FHR) short-term variability (STV) in early preterm fetal growth restriction (FGR) for prevention of fetal death and neonatal asphyxia, neonatal morbidity, and 2-year neurodevelopmental impairment., Methods: This was a retrospective cohort study of all women who were admitted to the Amsterdam University Medical Center-AMC between 2003 and 2015 due to FGR and/or pre-eclampsia, and who were delivered by prelabor Cesarean section, or had a fetal death, before 32 weeks' gestation. STV of all available cCTG registrations during the 5 days preceding fetal death or delivery was calculated retrospectively, and FHR decelerations were classified visually as absent, 1-2/h or recurrent (> 2/h). Adverse outcome endpoints were defined as fetal death, neonatal asphyxia at birth (including fetal death), neonatal death, major neonatal morbidity and 2-year neurodevelopmental outcome. A simulation analysis was performed to assess the incidence of adverse outcome using two thresholds for cCTG: (1) highly abnormal (STV < 2.6 ms before 29 weeks and < 3.0 ms thereafter, and/or recurrent FHR decelerations); and (2) moderately abnormal (STV < 3.5 ms before 29 weeks and < 4.0 ms thereafter, and/or recurrent FHR decelerations). Three management strategies were assessed using a strict schedule for the frequency of cCTG recordings: (1) cCTG without use of fetal arterial Doppler; (2) cCTG with additional fetal arterial Doppler after 29 weeks; and (3) cCTG with additional fetal arterial Doppler after 27 weeks., Results: Included were 367 pregnancies (3295 cCTG recordings), of which 20 resulted in fetal death and 347 were delivered by Cesarean section before the onset of labor. Cesarean delivery was indicated by fetal condition in 94% of cases and by maternal condition in 6%. Median gestational age at delivery was 30 (interquartile range (IQR), 28-31) weeks and median birth weight was 900 (IQR, 740-1090) g. Six cases of fetal death were not anticipated by standard practice using visual assessment of CTG. A last highly abnormal cCTG was associated with fetal death and with neonatal asphyxia (including fetal death; n = 99), but not with major neonatal morbidity and 2-year neurodevelopmental outcome. Moderately abnormal cCTG had no significant association with any endpoint. Simulation analysis showed that a strategy that combined cCTG results with umbilicocerebral ratio or umbilical absent or reversed end-diastolic flow could detect all fetal deaths., Conclusions: Computerized CTG in combination with fetal arterial Doppler, with a strict protocol for the frequency of recordings, is likely to be more effective than visual CTG assessment for preventing fetal death in early preterm FGR. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Introduction: Pregnant women faced with complications of pregnancy often require long-term hospital admission for maternal and/or fetal monitoring. Antenatal admissions cause a burden to patients as well as hospital resources and costs. A telemonitoring platform connected to wireless cardiotocography (CTG) and automated blood pressure (BP) devices can be used for telemonitoring in pregnancy. Home telemonitoring might improve autonomy and reduce admissions and thus costs. The aim of this study is to compare the effects on patient safety, satisfaction and cost-effectiveness of ho spital care versus tel emonitoring (HOTEL) as an obstetric care strategy in high-risk pregnancies requiring daily monitoring., Methods and Analysis: The HOTEL trial is an ongoing multicentre randomised controlled clinical trial with a non-inferiority design. Eligible pregnant women are >26+0 weeks of singleton gestation requiring monitoring because of pre-eclampsia (hypertension with proteinuria), fetal growth restriction, preterm rupture of membranes without contractions, recurrent reduced fetal movements or an intrauterine fetal death in a previous pregnancy.Randomisation takes place between traditional hospitalisation (planned n=208) versus telemonitoring (planned n=208) until delivery. Telemonitoring at home is facilitated with Sense4Baby CTG devices, Microlife BP monitor and daily telephone calls with an obstetric healthcare professional as well as weekly hospital visits.Primary outcome is a composite of adverse perinatal outcome, defined as perinatal mortality, 5 min Apgar <7 or arterial cord blood pH <7.05, maternal morbidity (eclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, thromboembolic event), neonatal intensive care admission and caesarean section rate. Patient satisfaction and preference of care will be assessed using validated questionnaires. We will perform an economic analysis. Outcomes will be analysed according to the intention to treat principle., Ethics and Dissemination: The study protocol was approved by the Ethics Committee of the Utrecht University Medical Center and the boards of all six participating centres. Trial results will be submitted to peer-reviewed journals., Trial Registration Number: NTR6076., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)