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Objectives: To investigate the relationship between total uterine artery blood volume flow rate (TVFR) and birth weight and gestational age at delivery, and to establish normal ranges of TVFR throughout pregnancy.Methods: This was a prospective cohort study of 334 nulliparous women booking antenatal care at University College London Hospital between August 2008 and September 2009. Women underwent a transabdominal ultrasound examination of uterine arteries for measurement of TVFR at 12, 20 and 24 weeks' gestation. Pregnancy outcomes were recorded and linear regression was used to study the relationship between TVFR and gestational age at delivery and birth weight.Results: A total of 551 ultrasound scans were performed. There was a significant, positive correlation between TVFR at 11-13 weeks (TVFR1) and at 22-26 weeks (TVFR3) and birth weight. For every 100-mL/min increase in TVFR1 and TVFR3, there was an increase in birth weight of 45 g and 27 g, respectively. There was also a positive association between TVFR1 and gestational age at delivery, with a 1.4-day increase in gestational age for every 100-mL/min increase of TVFR1.Conclusion: Ultrasound measurement of TVFR in the first trimester is significantly associated with both birth weight and gestational age at delivery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

The article focuses on a symposium on the association between surgical treatment of cervical intraepithelial neoplasia (CIN) and subsequent preterm birth held on February 16, 2015 in London, Great Britain. It is stated that CIN grades 2 and 3 that have been managed surgically were the main focus of the meeting.

Objective To explore whether the increased risk of preterm birth following treatment for cervical disease is limited to the first birth following colposcopy. Design Nested case-control study. Setting Twelve NHS hospitals in England. Population All nonmultiple births from women selected as cases or controls from a cohort of women with both colposcopy and a hospital birth. Cases had a preterm (20-36 weeks of gestation) birth. Controls had a term birth (38-42 weeks) and no preterm. Methods Obstetric, colposcopy and pathology details were obtained. Main outcome measures Adjusted odds ratio of preterm birth in first and second or subsequent births following treatment for cervical disease. Results A total of 2798 births (1021 preterm) from 2001 women were included in the analysis. The risk of preterm birth increased with increasing depth of treatment among first births post treatment [trend per category increase in depth, categories <10 mm, 10-14 mm, 15-19 mm, ≥20 mm: odds ratio ( OR) 1.23, 95% confidence interval (95% CI) 1.12-1.36, P < 0.001] and among second and subsequent births post treatment (trend OR 1.34, 95% CI 1.15-1.56, P < 0.001). No trend was observed among births before colposcopy ( OR 0.98, 95% CI 0.83-1.16, P = 0.855). The absolute risk of a preterm birth following deep treatments (≥15 mm) was 6.5% among births before colposcopy, 18.9% among first births and 17.2% among second and subsequent births post treatment. Risk of preterm birth (once depth was accounted for) did not differ when comparing first births post colposcopy with second and subsequent births post colposcopy (adjusted OR 1.15, 95% CI 0.89-1.49). Conclusions The increased risk of preterm birth following treatment for cervical disease is not restricted to the first birth post colposcopy; it remains for second and subsequent births. These results suggest that once a woman has a deep treatment she remains at higher risk of a preterm birth throughout her reproductive life. Tweetable abstract Risk of preterm birth following large treatments for cervical disease remains for second and subsequent births. [ABSTRACT FROM AUTHOR]

OP06.02: Conservative management of low-risk late fetal growth restriction: an evidence-based management protocol The aim of this study was to assess the benefit of conservative management at term of late fetal growth restricted (FGR) babies stratified as low risk according with a novel evidence based protocol. Conclusions Appropriate risk stratification with conservative management of low risk FGR at term is safe and associated with less adverse neonatal and maternal outcomes. [Extracted from the article]

An abstract of the conference paper "The accuracy of birth weight estimation using two-dimensional ultrasonography in extremely small fetuses," by R. A. Jawan, and colleagues is presented.

Objective To evaluate the use of second-trimester uterine artery (UtA) Doppler to predict adverse pregnancy outcome in women with extreme levels of fetoplacental proteins used for Down syndrome screening. Methods At a single institution, women screened for Down syndrome were offered second-trimester UtA Doppler examination if they had one of the following on analysis of maternal serum: pregnancy-associated plasma protein-A≤0.28 multiples of the median (MoM) (1% of screened population), inhibin ≥3.0 MoM (2%), human chorionic gonadotropin ≥4.0 MoM (2%), alphafetoprotein (AFP) ≥2.5 MoM (2%), estriol ≤0.5 MoM (1%). Abnormal UtA Doppler was defined as bilateral or unilateral notching or mean pulsatility index ≥1.45. Results Of 240 women studied, 92 (38.3%) had an adverse pregnancy outcome: small for gestational age (either <10th customized centile (SGA10) or <5th customized centile (SGA5)), low birth weight (LBW, <2.5 kg), preterm delivery (<37 + 0 weeks of gestation), fetal loss (late miscarriage or stillbirth), placental abruption and gestational hypertension. Of 167 women screened with all five hormones, those with two or more extreme levels (n = 18, 10.8%) were significantly at risk of adverse pregnancy outcome compared with those with only one marker (61.1% vs. 35.6%, P = 0.04). UtA Doppler was abnormal in 20% (32 of 159 women screened) and increased the risk of adverse pregnancy outcome (RR 2.5, 65.6% vs. 26.0%, P < 0.001). SGA10, SGA5 and LBW were significantly more common in women with abnormal UtA Doppler (RR 2.98, 56.2% vs. 18.9%, P < 0.001, RR 4.6, 43.7% vs. 9.4%, P < 0.001 and RR 4.4, 31.2% vs. 7.1%, P < 0.001, respectively). Women with normal Doppler examination still had a 26% risk of adverse pregnancy outcome. Conclusions In women with extreme levels of fetoplacental proteins used for Down syndrome screening, an abnormal second-trimester UtA Doppler examination confers a high risk of adverse pregnancy outcome and SGA in particular, but a normal examination does not rule out an adverse pregnancy outcome. [ABSTRACT FROM AUTHOR]

Impaired materno-placental perfusion causes two important obstetric complications, fetal growth restriction and preeclampsia. This study investigated whether adenoviral vector-mediated overexpression of vascular endothelial growth factor (VEGF) in the uterine arteries (UtAs) increases uterine artery blood flow (UBF). First-generation adenovirus vectors (5 × 1011 particles) containing the VEGF gene (Ad.VEGF-A or -D) or the β-galactosidase reporter gene (Ad.lacZ) were injected into the UtAs of pregnant sheep (n=6) at 88–102 days of gestation (term=145 days). UBF was measured using Doppler sonography before, and 4–7 days after injection. Mean UBF increased significantly from 233±156 (s.d.) ml min−1 to 753±415 ml min−1 following Ad.VEGF-A injection (P=0.005, n=5); Ad.lacZ infection had no significant effect. Organ bath experiments on uterine arterial sections 4–7 days after injection showed that, compared with Ad.lacZ vessels, Ad.VEGF-A-transduced vessels had a reduced contractile response to phenylephrine (Emax 148±10.9 vs Emax 228.2±27.5, P<0.05) but increased relaxation with bradykinin (pD2 (−log EC50) values 9.11±0.01 vs 8.65±0.11, P<0.05). Injection of Ad.VEGF-A into the UtAs increases UBF by enhancing vasodilatation. This may provide the basis for therapy in pregnancies complicated by uteroplacental insufficiency.Gene Therapy (2008) 15, 1344–1350; doi:10.1038/gt.2008.102; published online 19 June 2008 [ABSTRACT FROM AUTHOR]

The article examines the prevalence of fetal isolated short femur in a group of women screened for Down syndrome by the integrated test. It also compares the outcome of fetuses with isolated short femur in the mid-trimester with that of fetuses with normal femur length. Results reveal that isolated short femur in the mid-trimester fetus is related to fetal growth restriction and small-for-gestational age.

Objectives: To access the fetal sheep trachea by ultrasound-guided transthoracic injection in order to deliver gene therapy vectors or occlude the trachea with a detachable balloon.Methods: Fetal sheep were operated on at a mean gestational age of 102 (range, 81-116) days (term = 145 days). Under ultrasound guidance, either a 20-G spinal (for vector delivery) or a 16-G Kellett (for placement of an occlusive balloon) needle was inserted via the fetal thorax into the fetal trachea.Results: Using the 20-G spinal needle the trachea was accessed successfully in 33/36 fetuses, with 97% survival. Failure to inject was related to fetal position and gestational age. Blood vessel damage causing significant morbidity occurred in two fetuses (6%). Tracheal occlusion was achieved by puncturing the trachea with the 16-G needle and advancing an endoluminal balloon in three out of five attempts in a mean time of 17 (range, 16-19) min, with 100% survival. In one case, the balloon became sited within the accessory lobe bronchus and was not inflated. At postmortem examination 21 days later, all balloons remained inflated and occluded the trachea, and the lung-to-body weight ratio and airways morphometric indices were consistent with relative pulmonary hyperplasia in the obstructed lungs.Conclusions: Ultrasound-guided transthoracic tracheal puncture is a reliable technique in fetal sheep, with low morbidity and mortality. Using this technique, a detachable endotracheal balloon can be placed to provoke pulmonary growth. Advances in needle design and balloon size may improve the success rate. [ABSTRACT FROM AUTHOR]

Somatic gene delivery in utero is a novel approach to gene therapy for genetic disease based on the hypothesis that prenatal intervention may avoid the development of severe manifestations of early-onset disease, allow targeting of otherwise inaccessible tissues including expanding stem cell populations, induce tolerance against the therapeutic transgenic protein and thereby provide permanent somatic gene correction. This approach is particularly relevant in relation to prenatal screening programmes for severe genetic diseases as it could offer prevention as a third option to families faced with the prenatal diagnosis of a genetically affected child. Most investigations towards in utero gene therapy have been performed on mice and sheep fetuses as model animals for human disease and for the application of clinically relevant intervention techniques such as vector delivery by minimally invasive ultrasound guidance. Other animals such as dogs may serve as particular disease models and primates have to be considered in immediate preparation for clinical trials. Proof of principle for the hypothesis of fetal gene therapy has been provided during the last 2 years in mouse models for Crigler Najjar Disease, Leber's congenital amaurosis, Pompe's disease and haemophilia B showing long-term postnatal therapeutic effects and tolerance of the transgenic protein after in utero gene delivery. However, recently we have also observed a high incidence of liver tumours after in utero application of an early form of third-generation equine infectious anaemia virus vectors with SIN configuration. These findings highlight the need for more investigations into the safety and the ethical aspects of in utero gene therapy as well as for science-based public information on risks and benefits of this preventive gene therapy approach before application in humans can be contemplated.Gene Therapy (2005) 12, 1601–1607. doi:10.1038/sj.gt.3302632; published online 1 September 2005 [ABSTRACT FROM AUTHOR]

Objective: We examined the yield and quality of genomic deoxyribonucleic acid (DNA) extracted from various postmortem fetal tissues. Methods: Fetal tissues were collected at the time of autopsy, and DNA was subsequently extracted. The yield and DNA quality was assessed using ultraviolet spectrometry and agarose gel electrophoresis. We used polymerase chain reaction (PCR) to assess the DNA extracted for genomic testing. Results: The median (range) gestation of the fetuses was 22 (16-41) weeks and the postmortem interval was 5.5 (2-10) days. Non-degraded genomic DNA was successfully extracted from all fetal tissues. Liver tissue had the lowest quality and muscle the highest quality. DNA yield or purity was not influenced by the postmortem interval. Conclusion: High quality genomic DNA can be extracted from fetal muscle, despite postmortem intervals of several days. [ABSTRACT FROM AUTHOR]

EP20.09: Late fetal growth restriction at term: should all babies be delivered before 40 weeks? Between the low and high risk group there was no significant difference between severe neonatal outcome and maternal outcomes (10% v's 11% and 63% v's 65% p > 0.05). Appropriate risk stratification with delivery recommended after 40 weeks in small babies at low risk of complication is safe and could have beneficial effect on neonatal and long-term development. [Extracted from the article]

The new cohort was compared with a historical cohort of late FGR babies diagnosed with customised birth weight <10 SP th sp centile. The historical cohort had a significantly lower gestational age at delivery (38 weeks versus 38 weeks+6 days), lower birth weight 2439g versus 2591g, but similar gestational age at diagnosis, 31 weeks. A novel ultrasound evidence based management of late FGR babies using a conservative approach could improve neonatal outcome, at the expense of more interventions in labour. [Extracted from the article]

Preterm birth (PTB; delivery <37 weeks), the main cause of neonatal death worldwide, can lead to adverse neurodevelopmental outcomes, as well as lung and gut pathology. PTB can be associated with ascending vaginal infection. Previously, we have shown that ascending E. coli infection in pregnant mice induces PTB and reduces pup survival. Here, we demonstrate that this model recapitulates the pathology observed in human preterm neonates, namely neuroinflammation, lung injury and gut inflammation. In neonatal brains, there is widespread cell death, microglial activation, astrogliosis and reduced neuronal density. We also validate the utility of this model by assessing the efficacy of maternal cervical gene therapy with an adeno-associated viral vector containing human beta defensin 3; this improves pup survival and reduces Tnfa mRNA expression in perinatal pup brains exposed to E. coli. This model provides a unique opportunity to evaluate the therapeutic benefit of preterm labour interventions on perinatal pathology., (Copyright © 2025. Published by Elsevier Inc.)

Fetal growth restriction (FGR) is associated with uteroplacental insufficiency, and neurodevelopmental and structural brain deficits in the infant. It is currently untreatable. We hypothesised that treating the maternal uterine artery with vascular endothelial growth factor adenoviral gene therapy (Ad.VEGF-A 165 ) normalises offspring brain weight and prevents brain injury in a guinea pig model of FGR. Pregnant guinea pigs were fed a restricted diet before and after conception and received Ad.VEGF-A 165 (1 × 10 10 viral particles, n = 18) or vehicle (n = 18), delivered to the external surface of the uterine arteries, in mid-pregnancy. Pregnant, ad libitum-fed controls received vehicle only (n = 10). Offspring brain weight and histological indices of brain injury were assessed at term and 5-months postnatally. At term, maternal nutrient restriction reduced fetal brain weight and increased microglial ramification in all brain regions but did not alter indices of cell death, astrogliosis or myelination. Ad.VEGF-A 165 increased brain weight and reduced microglial ramification in fetuses of nutrient restricted dams. In adult offspring, maternal nutrient restriction did not alter brain weight or markers of brain injury, whilst Ad.VEGF-A 165 increased microglial ramification and astrogliosis in the hippocampus and thalamus, respectively. Ad.VEGF-A 165 did not affect cell death or myelination in the fetal or offspring brain. Ad.VEGF-A 165 normalises brain growth and markers of brain injury in guinea pig fetuses exposed to maternal nutrient restriction and may be a potential intervention to improve childhood neurodevelopmental outcomes in pregnancies complicated by FGR., (© 2024. The Author(s).)

Introduction: This study aims to investigate probe motion during full mid-trimester anomaly scans., Methods: We undertook a prospective, observational study of obstetric sonographers at a UK University Teaching Hospital. We collected prospectively full-length video recordings of routine second-trimester anomaly scans synchronized with probe trajectory tracking data during the scan. Videos were reviewed and trajectories analyzed using duration, path metrics (path length, velocity, acceleration, jerk, and volume) and angular metrics (spectral arc, angular area, angular velocity, angular acceleration, and angular jerk). These trajectories were then compared according to the participant level of expertise, fetal presentation, and patient BMI., Results: A total of 17 anomaly scans were recorded. The average velocity of the probe was 12.9 ± 3.4 mm/s for the consultants versus 24.6 ± 5.7 mm/s for the fellows (p = 0.02), the average acceleration 170.4 ± 26.3 mm/s 2 versus 328.9 ± 62.7 mm/s 2 (p = 0.02), and the average jerk 7491.7 ± 1056.1 mm/s 3 versus 14944.1 ± 3146.3 mm/s 3 (p = 0.02), the working volume 9.10 6  ± 4.10 6 mm 3 versus 29.10 6  ± 11.10 6 mm 3 (p = 0.03), respectively. The angular metrics were not significantly different according to the participant level of expertise, the fetal presentation, or to patients BMI., Conclusion: Some differences in the probe path metrics (velocity, acceleration, jerk and working volume) were noticed according to operator's level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In Canada, disparities between Indigenous and non-Indigenous Peoples continue to exist in health and education because of the past and current harms of racism and colonization. One step towards closing health gaps is clinicians who can provide health and social care services that are free of racism and mistrust. Indigenous health providers are in the best position to provide this culturally relevant and safe care to their own communities. Therefore, more Indigenous students graduating from health professional programs are required to meet these needs. Indigenous identity support can be a facilitator for Indigenous student academic success but developing one's Indigenous identity can be challenging in post-secondary education environments. We explored how Indigenous rehabilitation students expressed, and wanted to be supported in their identity and academic success., Methods: Using a narrative inquiry approach, we conducted interviews with seven students from the occupational, physical, and respiratory therapy programs of a Canadian university. Students were asked to tell their story of learning about, applying to, and being in their rehabilitation program and how their Indigenous identity impacted these experiences. Data analysis was conducted by Indigenous and non-Indigenous team members, analyzing the stories on interaction of the participant with (1) themselves and others, (2) time, and (3) situation or place., Results: The researchers developed seven mini-stories, one for each participant, to illustrate the variation between participant experiences in the development of their Indigenous and professional identity, before and during their rehabilitation program. The students appreciated the opportunities afforded to them by being admitted to their programs in a Indigenous Peoples category, including identity affirmation. However, for most students, being in this category came with feared and/or experienced stigma. The work to develop a health professional identity brought even more complexity to the already complex work of developing and maintaining an Indigenous identity in the colonized university environment., Conclusion: This study highlights the complexity of developing a rehabilitation professional identity as an Indigenous student. The participant stories call for universities to transform into an environment where Indigenous students can be fully accepted for their unique gifts and the identities given to them at birth., (© 2024. The Author(s).)

In obstetric ultrasound (US) scanning, the learner's ability to mentally build a three-dimensional (3D) map of the fetus from a two-dimensional (2D) US image represents a significant challenge in skill acquisition. We aim to build a US plane localization system for 3D visualization, training, and guidance without integrating additional sensors. This work builds on top of our previous work, which predicts the six-dimensional (6D) pose of arbitrarily oriented US planes slicing the fetal brain with respect to a normalized reference frame using a convolutional neural network (CNN) regression network. Here, we analyze in detail the assumptions of the normalized fetal brain reference frame and quantify its accuracy with respect to the acquisition of transventricular (TV) standard plane (SP) for fetal biometry. We investigate the impact of registration quality in the training and testing data and its subsequent effect on trained models. Finally, we introduce data augmentations and larger training sets that improve the results of our previous work, achieving median errors of 2.97 mm and 6.63° for translation and rotation, respectively.

Objective: To quantify the risks of mortality, morbidity and postnatal characteristics associated with extreme preterm fetal growth restriction (EP-FGR)., Design: The EVERREST (Do e s v ascular endothelial growth factor gene therapy saf e ly imp r ove outcome in seve r e e arly-onset fetal growth re st riction?) prospective multicentre study of women diagnosed with EP-FGR (singleton, estimated fetal weight (EFW) <3rd percentile, <600 g, 20 +0 -26 +6 weeks of gestation). The UK subgroup of EP-FGR infants (<36 weeks) were sex-matched and gestation-matched to appropriate for age (AGA) infants born in University College London Hospital (1:2 design, EFW 25th-75th percentile)., Setting: Four tertiary perinatal units (UK, Germany, Spain, Sweden)., Main Outcomes: Antenatal and postnatal mortality, bronchopulmonary dysplasia (BPD), sepsis, surgically treated necrotising enterocolitis (NEC), treated retinopathy of prematurity (ROP)., Results: Of 135 mothers recruited with EP-FGR, 42 had a stillbirth or termination of pregnancy (31%) and 93 had live births (69%). Postnatal genetic abnormalities were identified in 7/93 (8%) live births. Mean gestational age at birth was 31.4 weeks (SD 4.6). 54 UK-born preterm EP-FGR infants (<36 weeks) were matched to AGA controls. EP-FGR was associated with increased BPD (43% vs 26%, OR 3.6, 95% CI 1.4 to 9.4, p=0.01), surgical NEC (6% vs 0%, p=0.036) and ROP treatment (11% vs 0%, p=0.001). Mortality was probably higher among FGR infants (9% vs 2%, OR 5.0, 95% CI 1.0 to 25.8, p=0.054). FGR infants more frequently received invasive ventilation (65% vs 50%, OR 2.6, 95% CI 1.1 to 6.1, p=0.03), took longer to achieve full feeds and had longer neonatal stays (median difference 6.1 days, 95% CI 3.8 to 8.9 and 19 days, 95% CI 9 to 30 days, respectively, p<0.0001)., Conclusions: Mortality following diagnosis of EP-FGR is high. Survivors experience increased neonatal morbidity compared with AGA preterm infants., Trial Registration Number: NCT02097667., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To determine whether the Growth Assessment Protocol (GAP) affects the antenatal detection of large for gestational age (LGA) or maternal and perinatal outcomes amongst LGA babies., Design: Secondary analysis of a pragmatic open randomised cluster control trial comparing the GAP with standard care., Setting: Eleven UK maternity units., Population: Pregnant women and their LGA babies born at ≥36 +0  weeks of gestation., Methods: Clusters were randomly allocated to GAP implementation or standard care. Data were collected from electronic patient records. Trial arms were compared using summary statistics, with unadjusted and adjusted (two-stage cluster summary approach) differences., Main Outcome Measures: Rate of detection of LGA (estimated fetal weight on ultrasound scan above the 90th centile after 34 +0  weeks of gestation, defined by either population or customised growth charts), maternal and perinatal outcomes (e.g. mode of birth, postpartum haemorrhage, severe perineal tears, birthweight and gestational age, neonatal unit admission, perinatal mortality, and neonatal morbidity and mortality)., Results: A total of 506 LGA babies were exposed to GAP and 618 babies received standard care. There were no significant differences in the rate of LGA detection (GAP 38.0% vs standard care 48.0%; adjusted effect size -4.9%; 95% CI -20.5, 10.7; p = 0.54), nor in any of the maternal or perinatal outcomes., Conclusions: The use of GAP did not change the rate of antenatal ultrasound detection of LGA when compared with standard care., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objectives: There is limited prospective evidence to guide the management of late-onset fetal growth restriction (FGR) and its differentiation from small-for-gestational age. The aim of this study was to assess prospectively a novel protocol in which ultrasound criteria were used to classify women with suspected late FGR into two groups: those at low risk, who were managed expectantly until the anticipated date of delivery, and those at high risk, who were delivered soon after 37 weeks of gestation. We also compared the outcome of this prospective cohort with that of a historical cohort of women presenting similarly with suspected late FGR, in order to evaluate the impact of the new protocol., Methods: This was a prospective study of women with a non-anomalous singleton pregnancy at ≥ 32 weeks' gestation attending a tertiary hospital in London, UK, between February 2018 and September 2019, with estimated fetal weight (EFW) ≤ 10 th centile, or EFW > 10 th centile in addition to a decrease in fetal abdominal circumference of ≥ 50 centiles compared with a previous scan, umbilical artery Doppler pulsatility index > 95 th centile or cerebroplacental ratio < 5 th centile. Women were classified as low or high risk based on ultrasound and Doppler criteria. Women in the low-risk group were delivered by 41 weeks of gestation, unless they subsequently met high-risk criteria, whereas women in the high-risk group (EFW < 3 rd centile, umbilical artery Doppler pulsatility index > 95 th centile or EFW between 3 rd and 10 th centiles (inclusive) with abdominal circumference drop or abnormal Dopplers) were delivered at or soon after 37 weeks. The primary outcome was adverse neonatal outcome and included hypothermia, hypoglycemia, neonatal unit admission, jaundice requiring treatment, suspected infection, feeding difficulties, 1-min Apgar score < 7, hospital readmission and any severe adverse neonatal outcome (perinatal death, resuscitation using inotropes or mechanical ventilation, 5-min Apgar score < 7, metabolic acidosis, sepsis, and cerebral, cardiac or respiratory morbidity). Secondary outcomes were adverse maternal outcome (operative delivery for abnormal fetal heart rate) and severe adverse neonatal outcome. Women managed according to the new protocol were compared with a historical cohort of 323 women delivered prior to the implementation of the new protocol, for whom management was guided by individual clinician expertise., Results: Over 18 months, 321 women were recruited to the prospective cohort, of whom 156 were classified as low risk and 165 were high risk. Adverse neonatal outcome was significantly less common in the low-risk compared with the high-risk group (45% vs 58%; adjusted odds ratio (aOR), 0.6 (95% CI, 0.4-0.9); P = 0.022). There was no significant difference in the rate of adverse maternal outcome (18% vs 24%; aOR, 0.7 (95% CI, 0.4-1.2); P = 0.142) or severe adverse neonatal outcome (3.8% vs 8.5%; aOR, 0.5 (95% CI, 0.2-1.3); P = 0.153) between the low- and high-risk groups. Compared with women in the historical cohort classified retrospectively as low risk, low-risk women managed under the new protocol had a lower rate of adverse neonatal outcome (45% vs 58%; aOR, 0.6 (95% CI, 0.4-0.9); P = 0.026)., Conclusions: Appropriate risk stratification to guide management of late FGR was associated with a reduced rate of adverse neonatal outcome in low-risk pregnancies. In clinical practice, a policy of expectantly managing women with a low-risk late-onset FGR pregnancy at term could improve neonatal and long-term development. Randomized controlled trials are needed to assess the effect of an evidence-based conservative management protocol for late FGR on perinatal morbidity and mortality and long-term neurodevelopment. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To determine whether the Growth Assessment Protocol (GAP), as implemented in the DESiGN trial, is cost-effective in terms of antenatal detection of small-for-gestational-age (SGA) neonate, when compared with standard care., Methods: This was an incremental cost-effectiveness analysis undertaken from the perspective of a UK National Health Service hospital provider. Thirteen maternity units from England, UK, were recruited to the DESiGN (DEtection of Small for GestatioNal age fetus) trial, a cluster randomized controlled trial. Singleton, non-anomalous pregnancies which delivered after 24 + 0 gestational weeks between November 2015 and February 2019 were analyzed. Probabilistic decision modeling using clinical trial data was undertaken. The main outcomes of the study were the expected incremental cost, the additional number of SGA neonates identified antenatally and the incremental cost-effectiveness ratio (ICER) (cost per additional SGA neonate identified) of implementing GAP. Secondary analysis focused on the ICER per infant quality-adjusted life year (QALY) gained., Results: The expected incremental cost (including hospital care and implementation costs) of GAP over standard care was £34 559 per 1000 births, with a 68% probability that implementation of GAP would be associated with increased costs to sustain program delivery. GAP identified an additional 1.77 SGA neonates per 1000 births (55% probability of it being more clinically effective). The ICER for GAP was £19 525 per additional SGA neonate identified, with a 44% probability that GAP would both increase cost and identify more SGA neonates compared with standard care. The probability of GAP being the dominant clinical strategy was low (11%). The expected incremental cost per infant QALY gained ranged from £68 242 to £545 940, depending on assumptions regarding the QALY value of detection of SGA., Conclusion: The economic case for replacing standard care with GAP is weak based on the analysis reported in our study. However, this conclusion should be viewed taking into account that cost-effectiveness analyses are always limited by the assumptions made. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Prognosis of Alzheimer's disease (AD) progression has been recognized as a challenging problem due to the massive numbers of cognitive, and pathological features recorded for patients and controls. While there have been many studies investigated the diagnosis of dementia using pathological characteristics, predicting the advancement of the disease using cognitive elements has not been heavily studied particularly using technologies like artificial intelligence and machine learning. This research aims at evaluating items of the Alzheimer's Disease Assessment Scale-Cognitive 13 (ADAS-Cog-13) test to determine key cognitive items that influence the progression of AD. A methodology that consists of machine learning and feature selection (FS) techniques was designed, implemented, and then tested against real data observations (cases and controls) of the Alzheimer's Disease Neuroimaging Initiative (ADNI) repository with a narrow scope on cognitive items of the ADAS-Cog-13 test. Results obtained by ten-fold cross validation and using dissimilar classification and FS techniques revealed that the decision tree algorithm produced classification models with the best performing results from the cognitive items. For ADAS-Cog-13 test, memory and learning features including word recall, delayed word recall and word recognition were the key items pinpointing to AD advancement. When these three cognitive items are processed excluding demographics by C4.5 algorithm the models derived showed 82.90% accuracy, 87.60% sensitivity and 78.20% specificity.

Background: Reducing the rate of stillbirth is an international priority. At least half of babies stillborn in high-income countries are small for gestational-age (SGA). The Growth Assessment Protocol (GAP), a complex antenatal intervention that aims to increase the rate of antenatal detection of SGA, was evaluated in the DESiGN type 2 hybrid effectiveness-implementation cluster randomised trial (n = 13 clusters). In this paper, we present the trial process evaluation., Methods: A mixed-methods process evaluation was conducted. Clinical leads and frontline healthcare professionals were interviewed to inform understanding of context (implementing and standard care sites) and GAP implementation (implementing sites). Thematic analysis of interview text used the context and implementation of complex interventions framework to understand acceptability, feasibility, and the impact of context. A review of implementing cluster clinical guidelines, training and maternity records was conducted to assess fidelity, dose and reach., Results: Interviews were conducted with 28 clinical leads and 27 frontline healthcare professionals across 11 sites. Staff at implementing sites generally found GAP to be acceptable but raised issues of feasibility, caused by conflicting demands on resource, and variable beliefs among clinical leaders regarding the intervention value. GAP was implemented with variable fidelity (concordance of local guidelines to GAP was high at two sites, moderate at two and low at one site), all sites achieved the target to train &gt; 75% staff using face-to-face methods, but only one site trained &gt; 75% staff using e-learning methods; a median of 84% (range 78-87%) of women were correctly risk stratified at the five implementing sites. Most sites achieved high scores for reach (median 94%, range 62-98% of women had a customised growth chart), but generally, low scores for dose (median 31%, range 8-53% of low-risk women and median 5%, range 0-17% of high-risk women) were monitored for SGA as recommended., Conclusions: Implementation of GAP was generally acceptable to staff but with issues of feasibility that are likely to have contributed to variation in implementation strength. Leadership and resourcing are fundamental to effective implementation of clinical service changes, even when such changes are well aligned to policy mandated service-change priorities., Trial Registration: Primary registry and trial identifying number: ISRCTN 67698474. Registered 02/11/16. https://doi.org/10.1186/ISRCTN67698474 ., (© 2022. The Author(s).)

Background: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care., Methods and Findings: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes., Conclusions: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings., Trial Registration: This trial is registered with the ISRCTN registry, ISRCTN67698474., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: NM reports personal fees from Takeda, personal fees from RSM Consulting, personal fees from Novartis, outside the submitted work. BT is the Clinical Director of the Tommy’s National Centre for Maternity Improvement based at the Royal College of Obstetrics and Gynaecology (RCOG); the Centre’s objective is to translate the latest evidence into clinical practice in the UK. DAL has received support from Medtronic Ltd and Roche Diagnostics for research unrelated to that presented here. LP is clinical advisor [and from Sept 2021 deputy clinical director] for Healthcare Safety Investigation Branch maternity investigation programme, President of the British Intrapartum Care Society (BICS), invited member of some RCOG working groups and co-opted member of the British Maternal and Fetal Medicine Society (BMFMS) committee; she also received support from Pharmacosmos for clinical consultancy in work unrelated to that presented here.

Background: Perinatal inflammation combined with hypoxia-ischemia (HI) exacerbates injury in the developing brain. Therapeutic hypothermia (HT) is standard care for neonatal encephalopathy; however, its benefit in inflammation-sensitized HI (IS-HI) is unknown., Methods: Twelve newborn piglets received a 2 µg/kg bolus and 1 µg/kg/h infusion over 52 h of Escherichia coli lipopolysaccharide (LPS). HI was induced 4 h after LPS bolus. After HI, piglets were randomized to HT (33.5 °C 1-25 h after HI, n = 6) or normothermia (NT, n = 6). Amplitude-integrated electroencephalogram (aEEG) was recorded and magnetic resonance spectroscopy (MRS) was acquired at 24 and 48 h. At 48 h, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive brain cell death, microglial activation/proliferation, astrogliosis, and cleaved caspase-3 (CC3) were quantified. Hematology and plasma cytokines were serially measured., Results: Two HT piglets died. aEEG recovery, thalamic and white matter MRS lactate/N-acetylaspartate, and TUNEL-positive cell death were similar between groups. HT increased microglial activation in the caudate, but had no other effect on glial activation/proliferation. HT reduced CC3 overall. HT suppressed platelet count and attenuated leukocytosis. Cytokine profile was unchanged by HT., Conclusions: We did not observe protection with HT in this piglet IS-HI model based on aEEG, MRS, and immunohistochemistry. Immunosuppressive effects of HT and countering neuroinflammation by LPS may contribute to the observed lack of HT efficacy. Other immunomodulatory strategies may be more effective in IS-HI., Impact: Acute infection/inflammation is known to exacerbate perinatal brain injury and can worsen the outcomes in neonatal encephalopathy. Therapeutic HT is the current standard of care for all infants with NE, but the benefit in infants with coinfection/inflammation is unknown. In a piglet model of inflammation (LPS)-sensitized HI, we observed no evidence of neuroprotection with cooling for 24 h, based on our primary outcome measures: aEEG, MRS Lac/NAA, and histological brain cell death. Additional neuroprotective agents, with beneficial immunomodulatory effects, require exploration in IS-HI models., (© 2021. The Author(s).)

Purpose: In obstetric ultrasound (US) scanning, the learner's ability to mentally build a three-dimensional (3D) map of the fetus from a two-dimensional (2D) US image represents a major challenge in skill acquisition. We aim to build a US plane localisation system for 3D visualisation, training, and guidance without integrating additional sensors., Methods: We propose a regression convolutional neural network (CNN) using image features to estimate the six-dimensional pose of arbitrarily oriented US planes relative to the fetal brain centre. The network was trained on synthetic images acquired from phantom 3D US volumes and fine-tuned on real scans. Training data was generated by slicing US volumes into imaging planes in Unity at random coordinates and more densely around the standard transventricular (TV) plane., Results: With phantom data, the median errors are 0.90 mm/1.17[Formula: see text] and 0.44 mm/1.21[Formula: see text] for random planes and planes close to the TV one, respectively. With real data, using a different fetus with the same gestational age (GA), these errors are 11.84 mm/25.17[Formula: see text]. The average inference time is 2.97 ms per plane., Conclusion: The proposed network reliably localises US planes within the fetal brain in phantom data and successfully generalises pose regression for an unseen fetal brain from a similar GA as in training. Future development will expand the prediction to volumes of the whole fetus and assess its potential for vision-based, freehand US-assisted navigation when acquiring standard fetal planes., (© 2022. The Author(s).)

Background: Exposure to inflammation exacerbates injury in neonatal encephalopathy (NE). We hypothesized that brain biomarker mRNA, cytokine mRNA and microRNA differentiate inflammation (E. coli LPS), hypoxia (Hypoxia), and inflammation-sensitized hypoxia (LPS+Hypoxia) in an NE piglet model., Methods: Sixteen piglets were randomized: (i) LPS 2 μg/kg bolus; 1 μg/kg infusion (LPS; n = 5), (ii) Saline with hypoxia (Hypoxia; n = 6), (iii) LPS commencing 4 h pre-hypoxia (LPS+Hypoxia; n = 5). Total RNA was acquired at baseline, 4 h after LPS and 1, 3, 6, 12, 24, 48 h post-insult (animals euthanized at 48 h). Quantitative PCR was performed for cytokines (IL1A, IL6, CXCL8, IL10, TNFA) and brain biomarkers (ENO2, UCHL1, S100B, GFAP, CRP, BDNF, MAPT). MicroRNA was detected using GeneChip (Affymetrix) microarrays. Fold changes from baseline were compared between groups and correlated with cell death (TUNEL) at 48 h., Results: Within 6 h post-insult, we observed increased IL1A, CXCL8, CCL2 and ENO2 mRNA in LPS+Hypoxia and LPS compared to Hypoxia. IL10 mRNA differentiated all groups. Four microRNAs differentiated LPS+Hypoxia and Hypoxia: hsa-miR-23a, 27a, 31-5p, 193-5p. Cell death correlated with TNFA (R = 0.69; p < 0.01) at 1-3 h and ENO2 (R = -0.69; p = 0.01) at 48 h., Conclusions: mRNA and miRNA differentiated hypoxia from inflammation-sensitized hypoxia within 6 h in a piglet model. This information may inform human studies to enable triage for tailored neuroprotection in NE., Impact: Early stratification of infants with neonatal encephalopathy is key to providing tailored neuroprotection. IL1A, CXCL8, IL10, CCL2 and NSE mRNA are promising biomarkers of inflammation-sensitized hypoxia. IL10 mRNA levels differentiated all three pathological states; fold changes from baseline was the highest in LPS+Hypoxia animals, followed by LPS and Hypoxia at 6 h. miR-23, -27, -31-5p and -193-5p were significantly upregulated within 6 h of a hypoxia insult. Functional analysis highlighted the diverse roles of miRNA in cellular processes.

Background: Posterior fossa abnormalities (PFAs) are commonly identified within routine screening and are a frequent indication for fetal magnetic resonance imaging (MRI). Although biometric measurements of the posterior fossa (PF) are established on fetal ultrasound and MRI, qualitative visual assessments are predominantly used to differentiate PFAs., Objectives: This systematic review aimed to assess 2-dimensional (2D) biometric measurements currently in use for assessing the PF on fetal MRI to delineate different PFAs., Methods: The protocol was registered (PROSPERO ID CRD42019142162). Eligible studies included T2-weighted MRI PF measurements in fetuses with and without PFAs, including measurements of the PF, or other brain areas relevant to PFAs., Results: 59 studies were included - 6859 fetuses had 62 2D PF and related measurements. These included linear, area and angular measurements, representing measures of PF size, cerebellum/vermis, brainstem, and supratentorial measurements. 11 measurements were used in 10 or more studies and at least 1200 fetuses. These dimensions were used to characterise normal for gestational age, diagnose a range of pathologies, and predict outcome., Conclusion: A selection of validated 2D biometric measurements of the PF on fetal MRI may be useful for identification of PFA in different clinical settings. Consistent use of these measures, both clinically and for research, is recommended., (© 2020 John Wiley & Sons, Ltd.)

Early detection is the key to successfully tackling dementia, a neurocognitive condition common among the elderly. Therefore, screening using technological platforms such as mobile applications (apps) may provide an important opportunity to speed up the diagnosis process and improve accessibility. Due to the lack of research into dementia diagnosis and screening tools based on mobile apps, this systematic review aims to identify the available mobile-based dementia and mild cognitive impairment (MCI) apps using specific inclusion and exclusion criteria. More importantly, we critically analyse these tools in terms of their comprehensiveness, validity, performance, and the use of artificial intelligence (AI) techniques. The research findings suggest diagnosticians in a clinical setting use dementia screening apps such as ALZ and CognitiveExams since they cover most of the domains for the diagnosis of neurocognitive disorders. Further, apps such as Cognity and ACE-Mobile have great potential as they use machine learning (ML) and AI techniques, thus improving the accuracy of the outcome and the efficiency of the screening process. Lastly, there was overlapping among the dementia screening apps in terms of activities and questions they contain therefore mapping these apps to the designated cognitive domains is a challenging task, which has been done in this research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Autism spectrum disorder is a developmental disorder that describes certain challenges associated with communication (verbal and non-verbal), social skills, and repetitive behaviors. Typically, autism spectrum disorder is diagnosed in a clinical environment by licensed specialists using procedures which can be lengthy and cost-ineffective. Therefore, scholars in the medical, psychology, and applied behavioral science fields have in recent decades developed screening methods such as the Autism Spectrum Quotient and Modified Checklist for Autism in Toddlers for diagnosing autism and other pervasive developmental disorders. The accuracy and efficiency of these screening methods rely primarily on the experience and knowledge of the user, as well as the items designed in the screening method. One promising direction to improve the accuracy and efficiency of autism spectrum disorder detection is to build classification systems using intelligent technologies such as machine learning. Machine learning offers advanced techniques that construct automated classifiers that can be exploited by users and clinicians to significantly improve sensitivity, specificity, accuracy, and efficiency in diagnostic discovery. This article proposes a new machine learning method called Rules-Machine Learning that not only detects autistic traits of cases and controls but also offers users knowledge bases (rules) that can be utilized by domain experts in understanding the reasons behind the classification. Empirical results on three data sets related to children, adolescents, and adults show that Rules-Machine Learning offers classifiers with higher predictive accuracy, sensitivity, harmonic mean, and specificity than those of other machine learning approaches such as Boosting, Bagging, decision trees, and rule induction.