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Objective Design Setting Population Methods Main outcome measures Results Conclusions Severe early‐onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes.Superiority, double‐blind randomised controlled trial.A total of 20 UK fetal medicine units.Pregnancies affected by FGR, defined as an abdominal circumference below the tenth centile with absent end‐diastolic flow in the umbilical artery between 22+0 and 29+6 weeks of gestation.Treatment with sildenafil (25 mg three times/day) or placebo until delivery or 32 weeks of gestation.All infants alive at hospital discharge were assessed for cardiovascular function and cognitive, speech/language and neuromotor impairment at 2 years of age. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley‐III composite score of >85.In total, 135 women were randomised between November 2014 and July 2016 (70 to sildenafil and 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. In all, 75 babies (55.5%) were discharged alive, with 61 infants eligible for follow‐up (32 sildenafil and 29 placebo). One infant died (placebo), three mothers declined and ten mothers were uncontactable. There was no difference in neurodevelopment or blood pressure following treatment with sildenafil. Infants who received sildenafil had a larger head circumference at 2 years of age (median difference 49.2 cm, IQR 46.4–50.3, vs 47.2 cm, 95% CI 44.7–48.9 cm).Sildenafil therapy did not prolong pregnancy or improve perinatal outcomes and did not improve infant neurodevelopment in FGR survivors. Therefore, sildenafil should not be prescribed for this condition. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the incidence of antepartum stillbirth in relation to the distribution of neonatal/fetal weight for different gestational ages. Design: Prospective observational cohort study. Setting: Obstetric ultrasound departments in two UK maternity hospitals. Population: 168 966 women with singleton pregnancies attending for routine antenatal care. Methods: We examined the incidence of antepartum stillbirths, within different birthweight and fetal weight percentile subgroups, conditioning for gestational age. Main outcome measures: Incidence of antepartum stillbirth. Results: The risk of stillbirth progressively increased for lower birthweight. Considering the 25–75th percentile as the reference category, the relative risks for stillbirth at <37 weeks' gestation were 7.6 (95% confidence interval [CI] 5.7–10.2) <1st percentile, 2.6 (95% CI 1.8–3.7) 1 to 10th percentile, 1.4 (95% CI 0.9–2.1) 10 to 25th percentile, 0.8 (95% CI 0.4–1.5) 75 to 90th percentile, 0.8 (95% CI 0.4–1.7) 90 to 99th percentile, 0.9 (95% CI 0.3–2.5) >99th percentile. The respective values for births at ≥37 weeks' gestation were 5.0 (95% CI 2.9–8.9), 2.1 (95% CI 1.4–3.3), 1.4 (95% CI 0.9–2.1), 1.2 (95% CI 0.7–1.8), 1.0 (95% CI 0.6–1.8) and 4.0 (95% CI 1.8–9.3). The incidence of stillbirth in ongoing low‐risk singleton pregnancies gradually increases for smaller fetuses at any gestational point. The higher incidence (5.56%) was evident for fetal weight <1st percentile between 24 and 28 weeks' gestation. Conclusion: Fetal weight and the weight of the stillborn have a continuous association with the incidence of antepartum stillbirth which is affected by gestational age. [ABSTRACT FROM AUTHOR]

Background and Objectives: Over the last few years, great interest has arisen in the role of the cerebroplacental ratio (CPR) to identify low-risk pregnancies at higher risk of adverse pregnancy outcomes. This study aimed to assess the predictive capacity of the CPR for adverse perinatal outcomes in all uncomplicated singleton pregnancies attending an appointment at 40–42 weeks. Materials and Methods: This is a retrospective cohort study including all consecutive singleton pregnancies undergoing a routine prenatal care appointment after 40 weeks in three maternity units in Spain and the United Kingdom from January 2017 to December 2019. The primary outcome was adverse perinatal outcomes defined as stillbirth or neonatal death, cesarean section or instrumental delivery due to fetal distress during labor, umbilical arterial cord blood pH < 7.0, umbilical venous cord blood pH < 7.1, Apgar score at 5 min < 7, and admission to the neonatal unit. Logistic mixed models and ROC curve analyses were used to analyze the data. Results: A total of 3143 pregnancies were analyzed, including 537 (17.1%) with an adverse perinatal outcome. Maternal age (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01 to 1.04), body mass index (OR 1.04, 95% CI 1.03 to 1.06), racial origin (OR 2.80, 95% CI 1.90 to 4.12), parity (OR 0.36, 95% CI 0.29 to 0.45), and labor induction (OR 1.79, 95% CI 1.36 to 2.35) were significant predictors of adverse perinatal outcomes with an area under the ROC curve of 0.743 (95% CI 0.720 to 0.766). The addition of the CPR to the previous model did not improve performance. Additionally, the CPR alone achieved a detection rate of only 11.9% (95% CI 9.3 to 15) when using the 10th centile as the screen-positive cutoff. Conclusions: Our data on late-term unselected pregnancies suggest that the CPR is a poor predictor of adverse perinatal outcomes. [ABSTRACT FROM AUTHOR]

Objective: To investigate perinatal mortality, morbidity and obstetric intervention following the introduction of a universal late third‐trimester ultrasound scan for growth restriction. Design: Prospective cohort study. Setting: Oxfordshire (OUH), UK. Population Women with a non‐anomalous singleton pregnancy undergoing pregnancy care and term delivery at OUH with an estimated due date (EDD) of birth between 1 January 2014 and 30 September 2019. Methods: Universal ultrasound for fetal growth restriction between 35+0 and 36+6 weeks was introduced in 2016. The outcomes of the next 18 631 eligible term pregnancies were compared, adjusting for covariates and time, with the previous 18 636 who had clinically indicated ultrasounds only. 'Screen‐positives' for growth restriction were managed according to a pre‐determined protocol which included non‐intervention for some small‐for‐gestational‐age babies. Main Outcome Measures: Extended perinatal mortality, a composite of mortality or encephalopathy Grade II–III, and expedited birth. Other outcomes included composite adverse outcomes used elsewhere, detection of low birthweight and birth from 37+0 to 38+6 weeks. Results: Extended perinatal deaths decreased 27% and severe morbidity decreased 33% but neither change was statistically significant (adjusted odd ratio [aOR] 0.53, 95% confidence interval [C1] 00.18–1.56 and aOR 0.71, 95% CI 0.31–1.63). Expedited births changed from 35.2% to 37.7% (aOR 0.99, 95% CI 0.92–1.06). Birthweight (<10th centile) detection using fetal biometry alone was 31.4% and rose to 40.5% if all abnormal scan parameters were used. Conclusion: Improvements in mortality and severe morbidity subsequent to introducing a universal ultrasound for growth restriction are encouraging but remain unclear. Little change in intervention is possible. The antenatal detection of low birthweight remains poor but improves where markers of growth restriction are used. [ABSTRACT FROM AUTHOR]

Background The Medical Certificate of Stillbirth (MCS) records data about a baby's death after 24 weeks of gestation but before birth. Major errors that could alter interpretation of the MCS were widespread in two UK-based regional studies. Methods A multicentre evaluation was conducted, examining MCS issued 1 January 2018 to 31 December 2018 in 76 UK obstetric units. A systematic case-note review of stillbirths was conducted by Obstetric and Gynaecology trainees, generating individual 'ideal MCSs' and comparing these to the actual MCS issued. Anonymized central data analysis described rates and types of error, agreement and factors associated with major errors. Results There were 1120 MCSs suitable for assessment, with 126 additional submitted data sets unsuitable for accuracy analysis (total 1246 cases). Gestational age demonstrated 'substantial' agreement [K = 0.73 (95% CI 0.70–0.76)]. Primary cause of death (COD) showed 'fair' agreement [K = 0.26 (95% CI 0.24–0.29)]. Major errors [696/1120; 62.1% (95% CI 59.3–64.9%)] included certificates issued for fetal demise at <24 weeks' gestation [23/696; 3.3% (95% CI 2.2–4.9%)] or neonatal death [2/696; 0.3% (95% CI 0.1–1.1%)] or incorrect primary COD [667/696; 95.8% (95% CI 94.1–97.1%)]. Of 540/1246 [43.3% (95% CI 40.6–46.1%)] 'unexplained' stillbirths, only 119/540 [22.0% (95% CI 18.8–25.7%)] remained unexplained; the majority were redesignated as either fetal growth restriction [FGR: 195/540; 36.1% (95% CI 32.2–40.3%)] or placental insufficiency [184/540; 34.1% (95% CI 30.2–38.2)]. Overall, FGR [306/1246; 24.6% (95% CI 22.3–27.0%)] was the leading primary COD after review, yet only 53/306 [17.3% (95% CI 13.5–22.1%)] FGR cases were originally attributed correctly. Conclusion This study demonstrates widespread major errors in MCS completion across the UK. MCS should only be completed following structured case-note review, with particular attention on the fetal growth trajectory. [ABSTRACT FROM AUTHOR]

New Findings: What is the topic of this review?More than half of all pregnancies in the UK are exposed to adversity linked to increased problems in pregnancy for mothers and adverse outcomes for their children, but we do not know the mechanism(s) underpinning these relationships.What advances does it highlight?Studies in mice prove that placental endocrine insufficiency driven by genetic manipulation of imprinted genes in the offspring can concurrently drive fetal growth restriction, alterations in maternal caregiving and aberrant behaviour in wild‐type offspring exposed to an adverse environment. This suggests that placental endocrine insufficiency might contribute to the co‐morbidity of low birth weight, maternal depression and neurodevelopmental disorders observed in human populations. Prenatal adversity, which is estimated to impact more than half of all pregnancies in the UK, compromises fetal growth and increases the chances of stillbirth, prematurity and infant mortality. Beyond these immediate and highly visible problems, infants that survive carry the invisible burden of increased risk of some of the most common and pervasive diseases that impact human populations. In utero exposure to depression and anxiety is one adversity that has been linked to these poorer outcomes, suggesting that maternal mood disorders drive the outcomes. However, recent studies in animal models suggest that both the maternal mood disorders and the detrimental outcomes for children could be the result of the same underlying placental pathology. In these studies, genetically wild‐type rodent mothers exposed to placental endocrine insufficiency engaged in less pup‐focused behaviours and less self‐care. Genetically wild‐type rodent offspring raised in this abnormal environment exhibited increased anxiety‐like behaviours, with male offspring additionally exhibiting deficits in cognition and atypical social behaviour, with some evidence of depressive‐like symptoms. This work establishes experimentally that placental endocrine insufficiency alone is sufficient to drive atypical behaviour in both mothers and their offspring. Although there are some data to suggest that this phenomenon is relevant to human pregnancy, considerably more work is required. [ABSTRACT FROM AUTHOR]

Objective: To examine the predictive performance of the relevant guideline by the Royal College of Obstetricians and Gynaecologists (RCOG) for neonates that are small for gestational age (SGA), and to compare the performance of the RCOG guideline with that of our competing risks model for SGA. Design: Prospective observational study. Setting: Obstetric ultrasound departments in two UK maternity hospitals. Population: A total of 96 678 women with singleton pregnancies attending for routine ultrasound examination at 19–24 weeks of gestation. Methods: Risks for SGA for different thresholds were computed, according to the competing risks model using maternal history, second‐trimester estimated fetal weight, uterine artery pulsatility index and mean arterial pressure. The detection rates by the RCOG guideline scoring system and the competing risks model for SGA were compared, at the screen positive rate (SPR) derived from the RCOG guideline. Main outcome measures: Small for gestational age (SGA), <10th or <3rd percentile, for different gestational age thresholds. Results: At an SPR of 22.5%, as defined by the RCOG guideline, the competing risks model predicted 56, 72 and 81% of cases of neonates that are SGA, with birthweights of <10th percentile, delivered at ≥37, <37 and <32 weeks of gestation, respectively, which were significantly higher than the respective figures of 36, 44 and 45% achieved by the application of the RCOG guideline. The respective figures for neonates that were SGA with birthweights of <3rd percentile were 66, 79, 85 and 41, 45, 44%. Conclusion: The detection rate for neonates that were SGA with the competing risk approach is almost double than that obtained with the RCOG guideline. The competing risks approach for the prediction of SGA performs better than the existing RCOG guideline. The competing risks approach for the prediction of SGA performs better than the existing RCOG guideline. [ABSTRACT FROM AUTHOR]

Objective: Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVID-19 (PAN-COVID) study and the American Academy of Pediatrics (AAP) Section on Neonatal-Perinatal Medicine (SONPM) National Perinatal COVID-19 Registry.Methods: This was an analysis of data from the PAN-COVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARS-CoV-2 infection at any stage in pregnancy, and the AAP-SONPM National Perinatal COVID-19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARS-CoV-2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN-COVID results are presented overall for pregnancies with suspected or confirmed SARS-CoV-2 infection and separately in those with confirmed infection.Results: We report on 4005 pregnant women with suspected or confirmed SARS-CoV-2 infection (1606 from PAN-COVID and 2399 from AAP-SONPM). For obstetric outcomes, in PAN-COVID overall and in those with confirmed infection in PAN-COVID and AAP-SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (< 37 weeks' gestation) in 12.0% of all women in PAN-COVID, in 16.1% of those women with confirmed infection in PAN-COVID and in 15.7% of women in AAP-SONPM. Extreme preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN-COVID and 0.3% in AAP-SONPM. Neonatal SARS-CoV-2 infection was reported in 0.9% of all deliveries in PAN-COVID overall, in 2.0% in those with confirmed infection in PAN-COVID and in 1.8% in AAP-SONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a small-for-gestational-age (SGA) neonate were 8.2% in PAN-COVID overall, 9.7% in those with confirmed infection and 9.6% in AAP-SONPM. Mean gestational-age-adjusted birth-weight Z-scores were -0.03 in PAN-COVID and -0.18 in AAP-SONPM.Conclusions: The findings from the UK and USA registries of pregnancies with SARS-CoV-2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PAN-COVID study, although not in the AAP-SONPM study. The data presented support strong guidance for enhanced precautions to prevent SARS-CoV-2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy. Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: Fetal growth restriction (FGR) is associated with maternal cardiovascular changes. Sildenafil, a phosphodiesterase type-5 inhibitor, potentiates the actions of nitric oxide, and it has been suggested that it alters maternal hemodynamics, potentially improving placental perfusion. Recently, the Dutch STRIDER trial was stopped prematurely owing to excess neonatal mortality secondary to pulmonary hypertension. The main aim of this study was to investigate the effect of sildenafil on maternal hemodynamics in pregnancies with severe early-onset FGR.Methods: This was a cardiovascular substudy within a UK multicenter, placebo-controlled trial, in which 135 women with a singleton pregnancy and severe early-onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10th centile and absent/reversed end-diastolic flow in the umbilical artery on Doppler velocimetry, diagnosed between 22 + 0 and 29 + 6 weeks' gestation) were assigned randomly to receive either 25 mg sildenafil three times daily or placebo until 32 + 0 weeks' gestation or delivery. Maternal blood pressure (BP), heart rate (HR), augmentation index, pulse wave velocity (PWV), cardiac output, stroke volume (SV) and total peripheral resistance were recorded before randomization, 1-2 h and 48-72 h post-randomization, and 24-48 h postnatally. For continuous data, analysis was performed using repeated measures ANOVA methods including terms for timepoint, treatment allocation and their interaction.Results: Included were 134 women assigned randomly to sildenafil (n = 69) or placebo (n = 65) who had maternal BP and HR recorded at baseline. At 1-2 h post-randomization, compared with baseline values, sildenafil increased maternal HR by 4 bpm more than did placebo (mean difference, 5.00 bpm (95% CI, 1.00-12.00 bpm) vs 1.25 bpm (95% CI, -5.38 to 7.88 bpm); P = 0.004) and reduced systolic BP by 1 mmHg more (mean difference, -4.13 mmHg (95% CI, -9.94 to 1.44 mmHg) vs -2.75 mmHg (95% CI, -7.50 to 5.25 mmHg); P = 0.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60 m/s more than did placebo (mean difference, -0.90 m/s (95% CI, -1.31 to -0.51 m/s) vs -0.26 m/s (95% CI, -0.75 to 0.59 m/s); P = 0.001). Sildenafil was associated with a non-significantly greater decrease in SV index after 1-2 h post-randomization than was placebo (mean difference, -5.50 mL/m2 (95% CI, -11.00 to -0.50 mL/m2 ) vs 0.00 mL/m2 (95% CI, -5.00 to 4.00 mL/m2 ); P = 0.056).Conclusions: Sildenafil in a dose of 25 mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early-onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short- or long-term clinical impact on the mother. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Severe early-onset fetal growth restriction (FGR) predisposes to fetal death, neonatal death, neonatal morbidity and neurodisability. The use of placental biomarkers has been proposed for risk stratification in pre-eclampsia, but they could be equally useful in fetal growth restriction in aiding management.Objective: To determine the efficacy of angiogenic biomarkers at predicting adverse pregnancy outcome in severe early-onset fetal growth restriction.Study Design: This is a secondary analysis of the multicentre, placebo-controlled STRIDER UK randomised controlled trial of singleton pregnancies with severe early-onset fetal growth restriction. Women with FGR pregnancies between 22+0 and 29+6 weeks of gestation were randomly assigned to receive either sildenafil 25 mg three times daily or placebo until 32+0 weeks' gestation or delivery. We developed prediction models based upon maternal demographics (age, parity, blood pressure, preeclampsia, gestational hypertension), fetal biometric (estimated fetal weight) and Doppler measurements (Middle Cerebral Artery (MCA), Umbilical Artery (UA)) and maternal angiogenic biomarkers [placental growth factor (PlGF), soluble endoglin (sEng), soluble fms-like tyrosine kinase 1 (sFlt-1) and sFlt-1:PlGF ratio) using both univariate and multivariate analysis.Results: A complete data set was available for 105 of 135 randomised women. Multivariate regression analysis identified estimated fetal weight (EFW) and sFlt-1:PlGF as independent predictors of livebirth (EFW OR: 1.01 (1.008, 1.021); p < 0.001 and lower sFlt-1:PlGF ratio OR: 0.53 (0.284, 0.994); p = 0.048) and overall survival (EFW OR: 1.01 (1.006, 1.015); p < 0.001 and lower sFlt-1/PlGF ratio OR: 0.51 (0.286, 0.904); p = 0.021). EFW was a consistent predictor for all outcomes other than gestation at delivery. sFlt-1:PlGF ratio was a consistent predictor for all outcomes other than neonatal morbidity.Conclusions: In severe early-onset FGR pregnancies livebirth and overall survival can be predicted using a model involving EFW and sFlt-1:PlGF ratio. This model require validation in a larger cohort but may allow informed decision making about pregnancy management, especially in previable cases. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of maternal ethnicity on the risk of adverse perinatal outcome in pregnant women with chronic hypertension.Methods: Demographic and delivery data were collated of women with chronic hypertension and singleton pregnancy who delivered at one of three UK obstetric units between 2000 and 2014. Multivariable logistic regression models were used to calculate risk ratios (RR), according to ethnic group, for adverse perinatal outcome, adjusted for other maternal characteristics including age, parity, body mass index, smoking status, deprivation index and year of delivery. The impact of maternal ethnicity on birth-weight centile calculation was investigated by comparing the birth-weight centile chart customized for ethnicity (Gestation Related Optimal Weight; GROW) with a birth-weight centile calculator that does not adjust for that factor (INTERGROWTH-21st ).Results: The study cohort included 4481 pregnancies (4045 women) with chronic hypertension. Women of white ethnicity accounted for 47% (n = 2122) of the cohort and 36% (n = 1601) were of black, 8.5% (n = 379) of Asian and 8.5% (n = 379) of other ethnicity. The overall incidence of stillbirth was 1.6%, that of preterm birth < 37 weeks was 16% and that of fetal growth restriction (birth weight < 3rd centile) was 11%. Black women, compared with white women, had the highest risk for all adverse perinatal outcomes, with stillbirth occurring in 3.1% vs 0.6% of pregnancies (adjusted RR (aRR), 5.56 (95% CI, 2.79-11.09)), preterm birth < 37 weeks in 21% vs 11% (aRR, 1.70 (95% CI, 1.43-2.01)) and birth weight < 3rd centile in 15% vs 7.4% (aRR, 2.07 (95% CI, 1.71-2.51)). Asian women, compared with white women, were also at increased risk of adverse perinatal outcome, with stillbirth occurring in 1.6% vs 0.6% (aRR, 3.03 (95% CI, 1.11-8.28)), preterm birth < 37 weeks in 20% vs 11% (aRR, 1.82 (95% CI, 1.41-2.35)) and birth weight < 3rd centile in 12% vs 7.4% (aRR, 1.69 (95% CI, 1.24-2.30)). The sensitivity and specificity for prediction of infants requiring neonatal unit admission were 40% and 93%, respectively, for those with birth weight < 3rd centile according to GROW charts, compared with 16% and 96%, respectively, for those with birth weight < 3rd centile according to INTERGROWTH-21st charts.Conclusions: Black ethnicity, compared with white, is associated with the greatest risk of adverse perinatal outcome in women with chronic hypertension, even after adjusting for other maternal characteristics. Women of Asian ethnicity are also at increased risk, but to a lesser extent. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Background: Reducing stillbirth and early neonatal death is a national priority in the UK. Current evidence indicates this is potentially achievable through application of four key interventions within routine maternity care delivered as the National Health Service (NHS) England's Saving Babies' Lives care bundle. However, there is significant variation in the degree of implementation of the care bundle between and within maternity units and the effectiveness in reducing stillbirth and improving service delivery has not yet been evaluated. This study aims to evaluate the impact of implementing the care bundle on UK maternity services and perinatal outcomes.Methods: The Saving Babies' Lives Project Impact and Results Evaluation (SPiRE) study is a multicentre evaluation of maternity care delivered through the Saving Babies' Lives care bundle using both quantitative and qualitative methodologies. The study will be conducted in twenty NHS Hospital Trusts and will include approximately 100,000 births. It involves participation by both service users and care providers. To determine the impact of the care bundle on pregnancy outcomes, birth data and other clinical measures will be extracted from maternity databases and case-note audit from before and after implementation. Additionally, this study will employ questionnaires with organisational leads and review clinical guidelines to assess how resources, leadership and governance may affect implementation in diverse hospital settings. The cost of implementing the care bundle, and the cost per stillbirth avoided, will also be estimated as part of a health economic analysis. The views and experiences of service users and service providers towards maternity care in relation to the care bundle will be also be sought using questionnaires.Discussion: This protocol describes a pragmatic study design which is necessarily limited by the availability of data and limitations of timescales and funding. In particular there was no opportunity to prospectively gather pre-intervention data or design a phased implementation such as a stepped-wedge study. Nevertheless this study will provide useful practice-based evidence which will advance knowledge about the processes that underpin successful implementation of the care bundle so that it can be further developed and refined.Trial Registration: www.clinicaltrials.gov NCT03231007 (26th July 2017). [ABSTRACT FROM AUTHOR]

The grief of stillbirth continues to affect a large number of parents in the 21st century. In the UK, 17 sets of parents face the reality of a baby born dead each day, a tragic end to the months of excitement and anticipation of pregnancy. Our previous (2012) article explored the aetiology of stillbirths in high and low income countries and focused on possible global interventions to reduce rates. This update will focus more on the current UK situation, attempting to summarize causes and investigations as well as exploring current innovations aimed at improving identification of fetuses at risk. [ABSTRACT FROM AUTHOR]

Objective This study aims to compare recommendations from recently published national clinical guidelines for pregnancies complicated by fetal growth restriction (FGR). Materials and Methods Clinical guidelines informing best practice management of pregnancies with FGR issued by the American Congress of Obstetricians and Gynecologists, the Society of Obstetricians and Gynaecologists of Canada and the Royal College of Obstetricians and Gynaecologists in the United Kingdom are reviewed together with the published literature on this topic. Results Each of the guidelines uses different terminology to describe pregnancies affected by suboptimal fetal growth; all of them agree that an estimated fetal weight < 10th centile should alert clinicians to small fetal size. All guidelines describe risk factor screening for improved detection of FGR and acknowledge the limited accuracy achieved with fundal height measurement. No agreement is reached over the value of fetal weight customization. All colleges have varied opinions regarding methods of Doppler surveillance, however agree that umbilical artery Doppler is beneficial as primary surveillance tool. Conclusions The results of this review relay significant inconsistencies and call for an urgent and practical international consensus on this important and common clinical topic. Current data were used to develop a clinical practice guideline for Ireland, which will be presented in context with this review. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the relationships between nausea and vomiting in pregnancy and (a) fetal growth restriction; and (b) maternal caffeine metabolism and fetal growth restriction. A cohort of 2,643 pregnant women, aged 18-45 years, attending two UK maternity units between 8 and 12 weeks gestation, was recruited. A validated tool assessed caffeine intake at different stages of pregnancy and caffeine metabolism was assessed from a caffeine challenge test. Experience of nausea and vomiting of pregnancy was self-reported for each trimester. Adjustment was made for confounders, including salivary cotinine as a biomarker of current smoking status. There were no significant associations between fetal growth restriction and nausea and vomiting in pregnancy, even after adjustment for smoking and alcohol intake. There were no significant differences in the relationship between caffeine intake and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first ( p = 0.50) or second trimester ( p = 0.61) after adjustment for smoking, alcohol intake and caffeine half-life. There were also no significant differences in the relationship between caffeine half-life and fetal growth restriction between those experiencing symptoms of nausea and vomiting and those who did not, for either the first trimester ( p = 0.91) or the second trimester ( p = 0.45) after adjusting for smoking, alcohol intake and caffeine intake. The results from this study show no evidence that the relationship between maternal caffeine intake and fetal growth restriction is modified by nausea and vomiting in pregnancy. [ABSTRACT FROM AUTHOR]

Background: Reference values for umbilical artery Doppler indices are used clinically to assess fetal well-being. However, many studies that have produced reference charts have important methodologic limitations, and these result in significant heterogeneity of reported reference ranges., Objectives: To produce international gestational age-specific centiles for umbilical artery Doppler indices based on longitudinal data and the same rigorous methodology used in the original Fetal Growth Longitudinal Study of the INTERGROWTH-21 st Project., Study Design: In Phase II of the INTERGROWTH-21 st Project (the INTERBIO-21st Study), we prospectively continued enrolling pregnant women according to the same protocol from 3 of the original populations in Pelotas (Brazil), Nairobi (Kenya), and Oxford (United Kingdom) that had participated in the Fetal Growth Longitudinal Study. Women with a singleton pregnancy were recruited at <14 weeks' gestation, confirmed by ultrasound measurement of crown-rump length, and then underwent standardized ultrasound every 5±1 weeks until delivery. From 22 weeks of gestation umbilical artery indices (pulsatility index, resistance index, and systolic/diastolic ratio) were measured in a blinded fashion, using identical equipment and a rigorously standardized protocol. Newborn size at birth was assessed using the international INTERGROWTH-21 st Standards, and infants had detailed assessment of growth, nutrition, morbidity, and motor development at 1 and 2 years of age. The appropriateness of pooling data from the 3 study sites was assessed using variance component analysis and standardized site differences. Umbilical artery indices were modeled as functions of the gestational age using an exponential, normal distribution with second-degree fractional polynomial smoothing; goodness of fit for the overall models was assessed., Results: Of the women enrolled at the 3 sites, 1629 were eligible for this study; 431 (27%) met the entry criteria for the construction of normative centiles, similar to the proportion seen in the original fetal growth longitudinal study. They contributed a total of 1243 Doppler measures to the analysis; 74% had 3 measures or more. The healthy low-risk status of the population was confirmed by the low rates of preterm birth (4.9%) and preeclampsia (0.7%). There were no neonatal deaths and satisfactory growth, health, and motor development of the infants at 1 and 2 years of age were documented. Only a very small proportion (2.8%-6.5%) of the variance of Doppler indices was due to between-site differences; in addition, standardized site difference estimates were marginally outside this threshold in only 1 of 27 comparisons, and this supported the decision to pool data from the 3 study sites. All 3 Doppler indices decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age for each of the 3 indices are provided, as well as equations to allow calculation of any value as a centile and z scores. The mean pulsatility index according to gestational age = 1.02944 + 77.7456*(gestational age) -2 - 0.000004455*gestational age 3 ., Conclusion: We present here international gestational age-specific normative centiles for umbilical artery Doppler indices produced by studying healthy, low-risk pregnant women living in environments with minimal constraints on fetal growth. The centiles complement the existing INTERGROWTH-21 st Standards for assessment of fetal well-being., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Small-for-gestational-age (SGA) confers a higher perinatal risk of adverse outcomes. Birthweight cannot be accurately measured until delivery, therefore accurate estimated fetal weight (EFW) based on ultrasonography is important in identifying this high-risk population. We aimed to establish the sensitivity of detecting SGA infants antenatally in a unit with a selective third-trimester ultrasound policy and to investigate the association between EFW and birthweight in these babies., Material and Methods: A retrospective cohort study was conducted on non-anomalous singleton pregnancies delivered after 36 weeks of gestation where SGA (<10th percentile) was diagnosed at delivery. The EFW at the time of the third-trimester ultrasound scan was recorded using standard Hadlock formulae., Results: In 2017, there were 8392 non-anomalous singleton pregnancies live born after 36 weeks, excluding late bookers. 797 were live-born SGA <10th percentile for birthweight and 464 <5th percentile, who met our inclusion criteria. The antenatal detection rate of SGA was 19.6% for babies with birthweight <10th percentile and 24.1% <5th percentile. There was a significant correlation between the EFW and birthweight of fetuses undergoing ultrasound assessment within 2 weeks of delivery (P < .001, r = 0.73 (Pearson correlation). For these cases, EFW was greater than the birthweight in 65% of cases. After adjusting all EFWs using the discrepancy between EFW and actual birthweight for those babies born within 48 hours of the scan, the mean difference between the birthweight and adjusted EFW 7 days before delivery was 111 g (95% CI 87-136 g) and at 14 days was 200 g (95% CI 153-248 g). Despite adjusting the EFW, 61/213 cases (28.6%) apparently lost weight between the ultrasound scan and delivery., Conclusions: Small-for-gestational-age infants with a birthweight <10th percentile are poorly identified antenatally with little improvement for those <5th percentile. In SGA babies, ultrasound EFW overestimated birthweight. Discrepancies between birthweight and EFW are not explicable only by the limitations of third-trimester sonography, a reduction in fetal weight close to delivery in a proportion of liveborn SGA babies is plausible., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Small for gestational age is usually defined as an infant with a birthweight <10th centile for a population or customized standard. Fetal growth restriction refers to a fetus that has failed to reach its biological growth potential because of placental dysfunction. Small-for-gestational-age babies make up 28-45% of nonanomalous stillbirths, and have a higher chance of neurodevelopmental delay, childhood and adult obesity, and metabolic disease. The majority of small-for-gestational-age babies are not recognized before birth. Improved identification, accompanied by surveillance and timely delivery, is associated with reduction in small-for-gestational-age stillbirths. Internationally and regionally, detection of small for gestational age and management of fetal growth problems vary considerably. The aim of this review is to: summarize areas of consensus and controversy between recently published national guidelines on small for gestational age or fetal growth restriction; highlight any recent evidence that should be incorporated into existing guidelines; and identify future research priorities in this field. A search of MEDLINE, Google, and the International Guideline Library identified 6 national guidelines on management of pregnancies complicated by fetal growth restriction/small for gestational age published from 2010 onwards. There is general consensus between guidelines (at least 4 of 6 guidelines in agreement) in early pregnancy risk selection, and use of low-dose aspirin for women with major risk factors for placental insufficiency. All highlight the importance of smoking cessation to prevent small for gestational age. While there is consensus in recommending fundal height measurement in the third trimester, 3 specify the use of a customized growth chart, while 2 recommend McDonald rule. Routine third-trimester scanning is not recommended for small-for-gestational-age screening, while women with major risk factors should have serial scanning in the third trimester. Umbilical artery Doppler studies in suspected small-for-gestational-age pregnancies are universally advised, however there is inconsistency in the recommended frequency for growth scans after diagnosis of small for gestational age/fetal growth restriction (2-4 weekly). In late-onset fetal growth restriction (≥32 weeks) general consensus is to use cerebral Doppler studies to influence surveillance and/or delivery timing. Fetal surveillance methods (most recommend cardiotocography) and recommended timing of delivery vary. There is universal agreement on the use of corticosteroids before birth at <34 weeks, and general consensus on the use of magnesium sulfate for neuroprotection in early-onset fetal growth restriction (<32 weeks). Most guidelines advise using cardiotocography surveillance to plan delivery in fetal growth restriction <32 weeks. The recommended gestation at delivery for fetal growth restriction with absent and reversed end-diastolic velocity varies from 32 to ≥34 weeks and 30 to ≥34 weeks, respectively. Overall, where there is high-quality evidence from randomized controlled trials and meta-analyses, eg, use of umbilical artery Doppler and corticosteroids for delivery <34 weeks, there is a high degree of consistency between national small-for-gestational-age guidelines. This review discusses areas where there is potential for convergence between small-for-gestational-age guidelines based on existing randomized controlled trials of management of small-for-gestational-age pregnancies, and areas of controversy. Research priorities include assessing the utility of late third-trimester scanning to prevent major morbidity and mortality and to investigate the optimum timing of delivery in fetuses with late-onset fetal growth restriction and abnormal Doppler parameters. Prospective studies are needed to compare new international population ultrasound standards with those in current use., (Copyright © 2017. Published by Elsevier Inc.)