A systematic review of brachial plexus injuries after caesarean birth: challenging delivery?

BACKGROUND: Caesarean section (CS) is widely perceived as protective against obstetric brachial plexus injury (BPI), but few studies acknowledge the factors associated with such injury. The objectives of this study were therefore to aggregate cases of BPI after CS, and to illuminate risk factors for BPI. METHODS: Pubmed Central, EMBASE and MEDLINE databases were searched using free text: (“brachial plexus injury” or “brachial plexus injuries” or “brachial plexus palsy” or “brachial plexus palsies” or “Erb’s palsy” or “Erb’s palsies” or “brachial plexus birth injury” or “brachial plexus birth palsy”) and (“caesarean” or “cesarean” or “Zavanelli” or “cesarian” or “caesarian” or “shoulder dystocia”). Studies with clinical details of BPI after CS were included. Studies were assessed using the National Institutes for Healthy Study Quality Assessment Tool for Case Series, Cohort and Case-Control Studies. MAIN RESULTS: 39 studies were eligible. 299 infants sustained BPI after CS. 53% of cases with BPI after CS had risk factors for likely challenging handling/manipulation of the fetus prior to delivery, in the presence of considerable maternal or fetal concerns, and/or in the presence of poor access due to obesity or adhesions. CONCLUSIONS: In the presence of factors that would predispose to a challenging delivery, it is difficult to justify that BPI could occur due to in-utero, antepartum events alone. Surgeons should exercise care when operating on women with these risk factors

Fetal surgery for open spina bifida

Key content: Spina bifida is a congenital neurological condition with lifelong physical and mental effects. Open fetal repair of the spinal lesion has been shown to improve hindbrain herniation, ventriculoperitoneal shunting, independent mobility and bladder outcomes for the child and, despite an increased risk of prematurity, does not seem to increase the risk of neurodevelopmental impairment. Open fetal surgery is associated with maternal morbidity. Surgery at our institution is offered and performed according to internationally agreed criteria and protocols. Further evidence regarding long‐term outcomes, fetoscopic repair and alternative techniques is awaited. Learning objectives: To understand the clinical effects, potential prevention and prenatal diagnosis of spina bifida. To understand the rationale and evidence supporting the benefits and risks of fetal repair of open spina bifida. To understand the criteria defining those who are likely to benefit from fetal surgery. Ethical issues: The concept of the fetus as a patient, and issues surrounding fetal death or the need for resuscitation during fetal surgery. The associated maternal morbidity in a procedure performed solely for the benefit of the fetus/child. The financial implications of new surgical treatments

FetReg: Placental Vessel Segmentation and Registration in Fetoscopy Challenge Dataset

Fetoscopy laser photocoagulation is a widely used procedure for the treatment of Twin-to-Twin Transfusion Syndrome (TTTS), that occur in mono-chorionic multiple pregnancies due to placental vascular anastomoses. This procedure is particularly challenging due to limited field of view, poor manoeuvrability of the fetoscope, poor visibility due to fluid turbidity, variability in light source, and unusual position of the placenta. This may lead to increased procedural time and incomplete ablation, resulting in persistent TTTS. Computer-assisted intervention may help overcome these challenges by expanding the fetoscopic field of view through video mosaicking and providing better visualization of the vessel network. However, the research and development in this domain remain limited due to unavailability of high-quality data to encode the intra- and inter-procedure variability. Through the \textit{Fetoscopic Placental Vessel Segmentation and Registration (FetReg)} challenge, we present a large-scale multi-centre dataset for the development of generalized and robust semantic segmentation and video mosaicking algorithms for the fetal environment with a focus on creating drift-free mosaics from long duration fetoscopy videos. In this paper, we provide an overview of the FetReg dataset, challenge tasks, evaluation metrics and baseline methods for both segmentation and registration. Baseline methods results on the FetReg dataset shows that our dataset poses interesting challenges, offering large opportunity for the creation of novel methods and models through a community effort initiative guided by the FetReg challenge

Management of late-onset fetal growth restriction: pragmatic approach

OBJECTIVES: International guidelines recommend delivery from 37 weeks in small for gestational age (SGA) fetuses mostly because of stillbirth concerns. Differentiating SGA from late-onset fetal growth restriction (FGR) is challenged by the limited prospective evidence to guide management. We prospectively assessed a novel protocol that used ultrasound criteria to classify women with suspected late FGR into two groups: low-risk with expectant management until the expected date of delivery and high-risk with delivery soon after 37 weeks. Furthermore, we compared the outcome of this prospective cohort with a historical cohort of women similarly presenting with suspected late FGR, to evaluate the impact of implementation of the new protocol. METHODS: This was a prospective study in women with a singleton non-anomalous fetus at ≥32 weeks with any of the following inclusion criteria: estimated fetal weight (EFW) ≤10th centile, ≥50 centiles decrease of the abdominal circumference (AC) from previous scans, umbilical artery Doppler pulsatility index >95th centile or cerebroplacental ratio <5th centile. Women were stratified into low- or high-risk late FGR. Women in the low-risk group were delivered by 41 weeks unless meeting high-risk criteria for delivery later on, whereas women in the high-risk group (PAPP-A <0.4MoM, EFW <3rd centile, or EFW ≥3rd and ≤10th centile with AC drop or abnormal Dopplers) were delivered at 37 weeks. The primary outcome was adverse neonatal outcome including hypothermia, hypoglycemia, neonatal unit admission, jaundice requiring treatment, suspected infection, feeding difficulties, Apgar score <7 at 1 minute, hospital readmission and any of the severe adverse neonatal outcome (perinatal death, resuscitation using inotropes or mechanical ventilation, Apgar score <7 at 5 minutes, metabolic acidosis, sepsis, 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 with the new protocol were compared with a historical cohort where management was guided by individual clinician's expertise. RESULTS: Over 18 months (2018-2019), 321 women were included. Adverse neonatal outcome was significantly less common in low- (n=156) compared with high-risk fetus (n=165): 45 vs 57%; aOR, 0.6; 95% CI, 0.4-0.9; P=0.022. There was no significant difference in adverse maternal outcome (18% vs 24%; aOR, 0.7; 95% CI, 0.4-1.2; P=0.142) and severe adverse neonatal outcome (3.8% vs 8.5%; aOR: 0.5; 95% CI, 0.2-1.3; P=0.153) between low and high-risk group. Compared to women delivered prior to the implementation of the new protocol and classified retrospectively into low- and high-risk late FGR (n=323), there was a lower adverse neonatal outcome (45% vs 58%; aOR, 0.6; 95% CI, 0.4-0.9; P=0.026) in the low-risk late FGR clinic group. CONCLUSIONS: Appropriate risk classification to define management in low- and high-risk FGR groups was associated with reduced adverse neonatal outcome in the low-risk group. In clinical practice a policy of expectantly managing women with late-onset low-risk FGR pregnancies 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 of late FGR on perinatal morbidity, mortality and long-term neurodevelopment

Foetal loss after chorionic villus sampling and amniocentesis in twin pregnancies: A multicentre retrospective cohort study.

OBJECTIVE: We aimed to determine foetal losses for DCDA and MCDA twins following transabdominal CVS or amniocentesis performed <22+0  weeks. METHODS: Retrospective cohort study conducted in the UK and Belgium 01/01/00-01/06/20. Cases with unknown chorionicity, monochorionic complications or complex procedures were excluded. Uncomplicated DCDA and MCDA twins without invasive procedures were identified as controls. We reported foetal losses <24+0  weeks and losses of genetically and structurally normal foetuses. RESULTS: Outcomes were compared for DCDA foetuses; 258 after CVS with 3406 controls, 406 after amniocentesis with 3390 controls plus MCDA foetuses, 98 after CVS with 1124 controls, and 160 after amniocentesis with 1122 controls. There were more losses <24+0  weeks with both procedures in DCDA (CVS RR 5.54 95% CI 3.38-9.08, amniocentesis RR 2.36 95% CI 1.22-4.56) and MCDA twins (CVS RR 5.14 95% CI 2.51-10.54, amniocentesis RR 7.01 95% CI 3.86-12.74). Losses of normal foetuses were comparable to controls (DCDA CVS RR 0.39 95% CI 0.05-2.83, DCDA amniocentesis RR 1.16 95% CI 0.42-3.22, MCDA CVS RR 2.3 95% CI 0.71-7.56, and MCDA amniocentesis RR 1.93 95% CI 0.59-6.38). CONCLUSIONS: This study indicates increased foetal losses for DCDA and MCDA twins following CVS and amniocentesis with uncertain risk to normal foetuses

Diagnosis and management of selective fetal growth restriction in monochorionic twin pregnancies: A cross‐sectional international survey

Objective: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. Design: Cross‐sectional survey. Setting: International. Population: Clinicians involved in the management of MCDA twin pregnancies with sFGR. Methods: A structured, self‐administered survey. Main Outcome Measures: Clinical practices and attitudes to diagnostic criteria and management strategies. Results: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of 25% for the diagnosis of sFGR. For early‐onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early‐onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early‐onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early‐onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. Conclusions: There is significant variation in clinician practices and attitudes towards the management of early‐onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high‐level evidence to guide management

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

FERN: is it possible to conduct a randomised controlled trial of intervention or expectant management for early-onset selective fetal growth restriction in monochorionic twin pregnancy - protocol for a prospective multicentre mixed-methods feasibility study.

INTRODUCTION: Selective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin <10th centile and EFW discordance ≥25%, is associated with stillbirth and neurodisability for both twins. The condition poses unique management difficulties: on the one hand, continuation of the pregnancy carries a risk of death of the smaller twin, with a high risk of co-twin demise (40%) or co-twin neurological sequelae (30%). On the other, early delivery to prevent the death of the smaller twin may expose the larger twin to prematurity, with the associated risks of long-term physical, emotional and financial costs from neurodisability, such as cerebral palsy.When there is severe and early sFGR, before viability, delivery is not an option. In this scenario, there are currently three main management options: (1) expectant management, (2) selective termination of the smaller twin and (3) placental laser photocoagulation of interconnecting vessels. These management options have never been investigated in a randomised controlled trial (RCT). The best management option is unknown, and there are many challenges for a potential RCT. These include the rarity of the condition resulting in a small number of eligible pregnancies, uncertainty about whether pregnant women will agree to participate in such a trial and whether they will agree to be randomised to expectant management or active fetal intervention, and the challenges of robust and long-term outcome measures. Therefore, the main objective of the FERN study is to assess the feasibility of conducting an RCT of active intervention vs expectant management in monochorionic twin pregnancies with early-onset (prior to 24 weeks) sFGR. METHODS AND ANALYSIS: The FERN study is a prospective mixed-methods feasibility study. The primary objective is to recommend whether an RCT of intervention vs expectant management of sFGR in monochorionic twin pregnancy is feasible by exploring women's preference, clinician's preference, current practice and equipoise and numbers of cases. To achieve this, we propose three distinct work packages (WPs). WP1: A Prospective UK Multicentre Study, WP2A: a Qualitative Study Exploring Parents' and Clinicians' Views and WP3: a Consensus Development to Determine Feasibility of a Trial. Eligible pregnancies will be recruited to WP1 and WP2, which will run concurrently. The results of these two WPs will be used in WP3 to develop consensus on a future definitive study. The duration of the study will be 53 months, composed of 10 months of setup, 39 months of recruitment, 42 months of data collection, and 5 months of data analysis, report writing and recommendations. The pragmatic sample size for WP1 is 100 monochorionic twin pregnancies with sFGR. For WP2, interviews will be conducted until data saturation and sample variance are achieved, that is, when no new major themes are being discovered. Based on previous similar pilot studies, this is anticipated to be approximately 15-25 interviews in both the parent and clinician groups. Engagement of at least 50 UK clinicians is planned for WP3. ETHICS AND DISSEMINATION: This study has received ethical approval from the Health Research Authority (HRA) South West-Cornwall and Plymouth Ethics Committee (REC reference 20/SW/0156, IRAS ID 286337). All participating sites will undergo site-specific approvals for assessment of capacity and capability by the HRA. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. The results from the FERN project will be used to inform future studies. TRIAL REGISTRATION NUMBER: This study is included in the ISRCTN Registry (ISRCTN16879394) and the NIHR Central Portfolio Management System (CPMS), CRN: Reproductive Health and Childbirth Specialty (UKCRN reference 47201)

Diagnosis and management of selective fetal growth restriction in monochorionic twin pregnancies: A cross-sectional international survey.

OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN: Cross-sectional survey. SETTING: International. POPULATION: Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS: A structured, self-administered survey. MAIN OUTCOME MEASURES: Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of 25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life