Prenatal detection of placenta accreta spectrum using a sonographic checklist.

INTRODUCTION: The European Working Group for Abnormally Invasive Placenta proposed a checklist of ultrasound features for the antenatal detection of placenta accreta spectrum (PAS). This study aims to assess the performance of the checklist in identifying histopathologically confirmed PAS cases in a cohort with a high pre-test probability of PAS, and identify if particular features are associated with PAS. MATERIAL AND METHODS: This is a prospective multi-site cohort study conducted between 2018 and 2023. Consecutive patients who underwent ultrasound assessment for suspicion of PAS were included, and the sonographic checklist was completed at the time of ultrasound. Cases were defined as PAS where they had intraoperative findings as described by the International Federation of Gynecology and Obstetrics (FIGO) grading, and histopathological findings for hysterectomy and myometrial resection cases. All non-PAS cases in this study had placenta previa and at least one prior cesarean delivery. RESULTS: Seventy-eight participants met inclusion criteria, of whom 63 (80.7%) were diagnosed with PAS. Cesarean hysterectomy was performed in 49 cases (62.8%). Overall, third-trimester ultrasound performed at a median gestational age of 32 weeks (IQR 30-34 weeks) had a sensitivity of 0.84 (95% CI 0.73 to 0.92) and specificity of 0.73 (95% CI 0.45 to 0.92) for detecting PAS, with a positive and negative likelihood ratio of 3.15 (95% CI 1.35 to 7.35) and 0.22 (95% CI 0.11 to 0.41), respectively. Features most associated with PAS were abnormal placental lacunae (Odds Ratio [OR] 5.40 [95% CI 1.61 to 18.03] and myometrial thinning OR 6.87 [95% CI 1.93 to 24.4]). While many of the ultrasound features seen in PAS were also present in cases of placenta previa with prior Cesarean section, the median (IQR) number of features present in PAS cases was significantly higher than in the non-PAS placenta previa group (six features [3-8] vs. two features [0-3] p = 0.001). No case of non-PAS placenta previa had more than five features present. CONCLUSIONS: The use of a standardized sonographic checklist had a high sensitivity and good specificity for the detection of PAS in this prospective cohort of well-classified PAS cases.

Radiomic study of antenatal prediction of severe placenta accreta spectrum from MR imaging.

OBJECTIVE: We previously demonstrated the potential of radiomics for prediction of severe histological Placenta Accreta Spectrum (PAS) subtypes using T2-weighted MRI. We aim is to validate our model using an additional dataset. Secondly, we explore whether performance is improved using a new approach to develop a new multivariate radiomics model. METHODS: Multi-centre retrospective analysis conducted between 2018-2023. Inclusion criteria: MRI performed for suspicion of PAS from ultrasound, clinical findings of PAS at laparotomy and/or histopathological confirmation. Radiomic features were extracted from T2-weighted MRI. The previous multivariate model was validated. Secondly, a 5-radiomic feature random forest classifier was selected from a randomised feature selection scheme to predict invasive placenta increta PAS cases. Prediction performance was assessed based on several metrics including Area Under the Curve (AUC) of the receiver operating characteristic curve (ROC), sensitivity and specificity. RESULTS: We present 100 women (mean age 34.6 (±3.9) with PAS, 64 of whom had placenta increta. Firstly, we validated the previous multivariate model and found a Support Vector Machine classifier had a sensitivity of 0.620 (95% CI: 0.068; 1.0), specificity of 0.619 (95% CI: 0.059; 1.0), an AUC of 0.671 (95% CI: 0.440; 0.922) and accuracy of 0.602 (95% CI: 0.353; 0.817) for predicting placenta increta. From the new multivariate model, the best 5-feature subset selected via the random subset feature selection scheme comprised of 4 radiomic features and 1 clinical variable (number of previous caesareans). This clinical-radiomic model achieved an AUC of 0.713 (95% CI: 0.551; 0.854), accuracy of 0.695 (95% CI 0.563; 0.793), sensitivity of 0.843 (95% CI 0.682; 0.990) and specificity of 0.447 (95% CI 0.167; 0.667). CONCLUSION: We validated our previous model and present a new multivariate radiomic model for prediction of severe placenta increta from a well-defined, cohort of PAS cases. ADVANCES IN KNOWLEDGE: Radiomic features demonstrate good predictive potential for identifying placenta increta. This suggests radiomics may be a useful adjunct to clinicians caring for women with this high-risk pregnancy condition.

Splenic vein rupture in pregnancy: A case report and systematic review of the literature.

Splenic vein aneurysm (SVA) rupture is a rare clinical entity, with few case reports detailing its occurrence during pregnancy. We describe a case of a SVA rupture and present a systematic review of the literature in relation to splenic vein rupture, with or without aneurysm. Our case was of a 30-year-old woman, Para 4 at 37 weeks' gestation who presented with significant abdominal pain and subsequent maternal collapse. Massive intra-abdominal hemorrhage was identified, with splenic vessel rupture suspected. A splenectomy and partial pancreatectomy were performed along with massive blood product transfusion. There was both maternal and fetal survival with no long-term sequelae at follow-up. Histological examination of the spleen and its vessels noted a SVA rupture. In a subsequent systematic review of the literature, we identified 10 cases of splenic vein rupture with only two previously documented cases of SVA rupture in pregnancy. Maternal and fetal survival has only been reported in two cases of splenic vein rupture, with ours being a third.

The importance of collaboration in maternal medicine: A retrospective descriptive study of a maternal multidisciplinary team meeting.

OBJECTIVE: In the present study we aimed to review the evolution and function of the maternal medicine multidisciplinary team (MMMDT) meeting of a maternal medicine service of a tertiary level stand-alone maternity hospital. METHODS: We conducted a retrospective descriptive study of all minutes of MMMDT meetings from 2014 to 2020, with the aim of evaluating meeting characteristics and patient demographics. RESULTS: There were 575 multidisciplinary team (MDT) discussions of 486 women during 43 meetings in the 7 year period. On average, 13 (range 3-23; SD = 5.28) women were discussed at each meeting, attended by 17 (range: 11-27; SD = 4.26) attendees. There were 18 women discussed during successive pregnancies. When analyzing the 2017-2020 data, preconceptual discussions made up 7.3% (n = 42) of patients discussed, with 5.7% (n = 33) being postnatal. The mean maternal age was 32.5 years (range 15-48 years) and women were most likely to be discussed in the mid-trimester period (21-24 weeks gestation). The top five primary specialities involved were hematology, neurology, rheumatology, neurosurgery and gastroenterology; however, 22 specialities were represented overall when classified by the primary medical condition. When examining the MDT input, hematology input was required in 144 patients (25.0%), radiology in 161 (28.0%) patients, and 117 in anesthesiology (20.3%). When examining the number of teams required to manage the patient, 80 women required the input of three specialities, with 16 women requiring the input of four specialities. CONCLUSION: We demonstrate the value and role of the MDT in the management of complex patients, providing a forum to discuss care in all phases of the obstetric journey.

Private practice dietetics: A scoping review of the literature.

AIM: Private practice is one of the most rapidly growing, but under-researched employment sectors for graduate dietitians in Australia, limiting evidence-based workforce development. This scoping review examines existing international literature to gain an understanding of the current private practice workforce size, distribution, demography and workforce development considerations, including competencies, supply and demand, remuneration and professional development activities. METHODS: The databases MEDLINE, EMBASE, CINAHL, EMCARE, PsycInfo (Ovid) and grey literature were systematically searched in August 2023 using key search terms to identify studies for inclusion. Articles were included if they related to private practice dietetics and described an aspect of workforce. Original research, government and organisational reports, statements of practice and websites providing governmental or organisational statistics were included. A directed content analysis and qualitative constant comparison technique were used to deductively map intelligence sources against a workforce development framework. A gap analysis was also conducted to provide a focus for future workforce development research. RESULTS: A total of 72 peer-reviewed and grey literature sources were included, with 65% of the studies being Australian-based publications. Private practice dietetics research interest has increased in the last decade. Despite a breadth of published sources, this review found little published data on workforce size, distribution, demography, supply, demand, continued professional development and remuneration, indicating a significant gap in the evidence base. Existing literature focuses on workforce challenges and barriers, the work of private practice dietitians, with limited exploration of competency requirements for graduate private practitioners. CONCLUSIONS: The literature on the private practice dietetics workforce is lacking worldwide, which constrains evidenced-based workforce development initiatives. Workforce development research across all workforce aspects is warranted to address current evidence gaps.

VTE risk assessment, prevention and diagnosis in pregnancy.

Venous thromboembolism (VTE) is still reported as the leading cause of direct maternal death in pregnancy in serial international reports in developed countries. VTE risk is higher during pregnancy but is further increased by additional well-characterized risk factors. International guidelines recommend that formal VTE risk assessment should be conducted at least in early pregnancy, at delivery and when risk factors change. High quality data supporting optimal VTE prevention strategies are lacking, outside the setting of prevention of VTE recurrence. Moreover, recent high-quality studies have provided much-needed data on diagnostic strategies for pulmonary embolism (PE) in pregnancy. In this review, we summarize knowledge gaps and recently published data in the prevention and diagnosis of VTE in pregnancy. Moreover, we describe ongoing high-quality randomised trials and prospective clinical management studies in this area. High quality clinical studies and trials in pregnancy can be done and must be prioritised, through international network efforts and national funding advocacy. Ultimately, translation of study results to impact upon guidelines and policy will deliver better care to and will protect the lives and health of pregnant people and those contemplating pregnancy throughout the world.

Validating the safety of low-dose CTPA in pregnancy: results from the OPTICA (Optimised CT Pulmonary Angiography in Pregnancy) Study.

BACKGROUND: Pulmonary embolism (PE) is a leading cause of pregnancy-related mortality. CT pulmonary angiogram (CTPA) is the first-line advanced imaging modality for suspected PE in pregnancy at institutes offering low-dose techniques; however, a protocol balancing safety with low dose remains undefined. The wide range of CTPA doses reported in pregnancy suggests a lack of confidence in implementing low-dose techniques in this group. PURPOSE: To define and validate the safety, radiation dose and image quality of a low-dose CTPA protocol optimised for pregnancy. MATERIALS AND METHODS: The OPTICA study is a prospective observational study. Pregnant study participants with suspected PE underwent the same CTPA protocol between May 2018 and February 2022. The primary outcome, CTPA safety, was judged by the reference standard; the 3-month incidence of venous thromboembolism (VTE) in study participants with a negative index CTPA. Secondary outcomes defined radiation dose and image quality. Absorbed breast, maternal effective and fetal doses were estimated by Monte-Carlo simulation on gestation-matched phantoms. Image quality was assessed by signal-to-noise and contrast-to-noise ratios and a Likert score for pulmonary arterial enhancement. RESULTS: A total of 116 CTPAs were performed in 113 pregnant women of which 16 CTPAs were excluded. PE was diagnosed on 1 CTPA and out-ruled in 99. The incidence of recurrent symptomatic VTE was 0.0% (one-sided 95% CI, 2.66%) at follow-up. The mean absorbed breast dose was 2.9 ± 2.1mGy, uterine/fetal dose was 0.1 ± 0.2mGy and maternal effective dose was 1.4 ± 0.9mSv. Signal-to-noise ratio (SNR) was 11.9 ± 3.7. Contrast-to-noise ratio (CNR) was 10.4 ± 3.5. CONCLUSION: The OPTICA CTPA protocol safely excluded PE in pregnant women across all trimesters, with low fetal and maternal radiation. CLINICAL RELEVANCE: OPTICA (Optimised CT Pulmonary Angiography in Pregnancy) is the first prospective study to define the achievable radiation dose, image-quality and safety of a low-dose CT pulmonary angiogram protocol optimised for pregnancy (NCT04179487). It provides the current benchmark for safe and achievable CT pulmonary angiogram doses in the pregnant population. KEY POINTS: • Despite the increased use of CT pulmonary angiogram in pregnancy, an optimised low-dose protocol has not been defined and reported doses in pregnancy continue to vary widely. • The OPTICA (Optimised CT Pulmonary Angiography in Pregnancy) study prospectively defines the achievable dose, image quality and safety of a low-dose CT pulmonary angiogram protocol using widely available technology. • OPTICA provides a benchmark for safe and achievable CT pulmonary angiogram doses in the pregnant population.

Radiomics-based prediction of FIGO grade for placenta accreta spectrum.

BACKGROUND: Placenta accreta spectrum (PAS) is a rare, life-threatening complication of pregnancy. Predicting PAS severity is critical to individualise care planning for the birth. We aim to explore whether radiomic analysis of T2-weighted magnetic resonance imaging (MRI) can predict severe cases by distinguishing between histopathological subtypes antenatally. METHODS: This was a bi-centre retrospective analysis of a prospective cohort study conducted between 2018 and 2022. Women who underwent MRI during pregnancy and had histological confirmation of PAS were included. Radiomic features were extracted from T2-weighted images. Univariate regression and multivariate analyses were performed to build predictive models to differentiate between non-invasive (International Federation of Gynecology and Obstetrics [FIGO] grade 1 or 2) and invasive (FIGO grade 3) PAS using R software. Prediction performance was assessed based on several metrics including sensitivity, specificity, accuracy and area under the curve (AUC) at receiver operating characteristic analysis. RESULTS: Forty-one women met the inclusion criteria. At univariate analysis, 0.64 sensitivity (95% confidence interval [CI] 0.0-1.00), specificity 0.93 (0.38-1.0), 0.58 accuracy (0.37-0.78) and 0.77 AUC (0.56-.097) was achieved for predicting severe FIGO grade 3 PAS. Using a multivariate approach, a support vector machine model yielded 0.30 sensitivity (95% CI 0.18-1.0]), 0.74 specificity (0.38-1.00), 0.58 accuracy (0.40-0.82), and 0.53 AUC (0.40-0.85). CONCLUSION: Our results demonstrate a predictive potential of this machine learning pipeline for classifying severe PAS cases. RELEVANCE STATEMENT: This study demonstrates the potential use of radiomics from MR images to identify severe cases of placenta accreta spectrum antenatally. KEY POINTS: • Identifying severe cases of placenta accreta spectrum from imaging is challenging. • We present a methodological approach for radiomics-based prediction of placenta accreta. • We report certain radiomic features are able to predict severe PAS subtypes. • Identifying severe PAS subtypes ensures safe and individualised care planning for birth.

Psychosocial factors and chronic spontaneous urticaria: a systematic review.

BACKGROUND: Psychosocial factors have been informally associated with Chronic Spontaneous Urticaria (CSU); however, the relationship between psychosocial factors and CSU remains relatively unexplored in the scientific literature. OBJECTIVE: This review aims to provide an evaluation of peer reviewed studies exploring psychosocial factors and CSU. METHODS: A systematic search was performed over four databases identifying studies exploring psychosocial factors in relation to CSU published between the years 1995 and 2022. RESULTS: Eighteen studies were included for narrative analysis, and 33 psychosocial factors were identified. These were split into two subgroups: psychosocial factors that were associated with CSU symptoms aggravation/onset (n = 20), and psychosocial factors expected to be impacted by CSU symptoms (n = 13). CONCLUSION: This review has highlighted a need for more research and interventions to support individuals with psychosocial factors involved in CSU.

Use of an aortic balloon to achieve uterine conservation in a case of placenta accreta spectrum: A case report.

Placenta accreta spectrum (PAS) is a rare complication of pregnancy associated with a high risk of massive haemorrhage and caesarean hysterectomy. This is a case report of abdominal aortic balloon occlusion, using intravascular ultrasound, to achieve uterine conservation in a case of severe PAS. The patient was a 34-year-old woman, G2P1, with one prior caesarean section. Antenatal imaging, consisting of transabdominal and transvaginal ultrasound, and magnetic resonance imaging, showed features of PAS. The risk of caesarean hysterectomy with PAS was explained, but the patient declared a desire to retain fertility. Following multi-disciplinary discussion, it was considered appropriate to attempt uterine conservation using en-bloc myometrial and placental resection. An elective caesarean delivery was performed at 36 weeks of gestation. An aortic balloon was inserted prior to surgery using intravascular ultrasound, which allowed for radiation-free, point-of-surgery, accurate balloon sizing, by measuring the aortic diameter, and correct placement of the balloon in the abdominal aorta below the renal vessels. Intraoperative findings confirmed PAS, and a myometrial resection was performed. There were no intraoperative complications. Estimated blood loss was 1000 mL and the patient had an uncomplicated postoperative course. This case demonstrates how the use of an intravascular intraoperative aortic balloon can facilitate uterine conservation in a case of severe PAS.

Management of Hemorrhage During Cesarean Delivery in a Patient With Vascular Ehlers-Danlos Syndrome: A Case Report.

Parturients with vascular Ehlers-Danlos syndrome are at particular risk of hemorrhage, and there is little evidence to guide prevention or management of hemorrhage in these patients. We present the case of a patient with vascular Ehlers-Danlos syndrome who had a cesarean delivery complicated by an intraoperative hemorrhage. Administration of desmopressin and tranexamic acid appeared to be of marked benefit in achieving hemostasis. To the best of our knowledge, this is the first report of the use of desmopressin during major obstetric hemorrhage in vascular Ehlers-Danlos syndrome.

Onset of labor and use of analgesia in women using thromboprophylaxis with 2 doses of low-molecular-weight heparin: insights from the Highlow study.

BACKGROUND: Peripartum management of women using low-molecular-weight heparin (LMWH) varies widely. Minimum time intervals are required between LMWH injection and neuraxial procedure, and they differ by dose. OBJECTIVES: The objective of this study was to describe the onset of labor and use of analgesia in women using LMWH and to compare practices between intermediate-dose and low-dose LMWH. METHODS: In the Highlow study (NCT01828697), 1110 women were randomized to intermediate-dose or low-dose LMWH and were instructed to discontinue LMWH when labor commenced unplanned or 24 hours prior to planned delivery. The required time interval since last injection to receive a neuraxial procedure was ≥24 hours for intermediate-dose LMWH or ≥12 hours for low-dose LMWH. RESULTS: In total, 1018 women had an ongoing pregnancy for ≥24 weeks. Onset of labor was spontaneous in 198 of 509 (39%) women on intermediate-dose LMWH and in 246 of 509 (49%) on low-dose LMWH. With unplanned onset, a neuraxial procedure was performed in 37% on intermediate-dose and in 48% on low-dose LMWH (risk difference -11%, 95% CI -20% to -2%). Based on time interval, 61% on intermediate-dose and 82% on low-dose LMWH were eligible for a neuraxial procedure. With planned onset, 68% on intermediate-dose and 66% on low-dose LMWH received a neuraxial procedure, whereas 81% and 93%, respectively, were eligible for a neuraxial procedure (risk difference -13%, 95% CI -18% to -8%). CONCLUSION: With spontaneous onset of labor, neuraxial procedures were performed less often in women using intermediate-dose LMWH. Irrespective of onset, fewer women on intermediate-dose LMWH than those on low-dose LMWH were eligible for neuraxial procedures based on required time intervals since the last LMWH injection.

Placenta accreta spectrum ultrasound stage and fetal growth.

OBJECTIVE: to evaluate fetal growth in pregnancies complicated by placenta accreta spectrum (PAS) and to compare fetal growth between cases stratified by ultrasound stage of PAS. METHODS: This was a prospective multicenter cohort study of women diagnosed with PAS between January 2018 and December 2021. We grouped participants into cases by ultrasound stage (PAS stage 1-3) and controls (PAS0). Fetal growth centiles at three timepoints with median gestational ages of 21 ± 1 weeks (interquartile range [IQR], 20 ± 1-22 ± 0 weeks), 28 ± 0 weeks (IQR, 27 ± 0-28 ± 5 weeks), and 33 ± 0 weeks (IQR, 32 ± 1-34 ± 0 weeks) and birth weight centiles were compared between cases and controls and between those with PAS stratified by ultrasound stage. RESULTS: A total of 53 women met inclusion criteria, with a mean age of 37 years (standard deviation, ±4.0 years) and body mass index of 27 kg/m2 (standard deviation, ±5.8 kg/m2 ). Median (IQR) fetal weight centiles were around the 50th centile at each timepoint, with no difference between groups. The incidence of small for gestational age (birth weight ≤ 10th percentile) and large for gestational age (birth weight ≥ 90th percentile) was 11.3% (n = 6) and 15.1% (n = 8), respectively, with no differences by ultrasound stage. The median birth weight centile was 64 (IQR, 26-85), with no differences between cases and controls or by ultrasound stage. CONCLUSIONS: In our cohort, a diagnosis of PAS was not associated with fetal growth restriction.

Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: Pregnancy-related venous thromboembolism is a leading cause of maternal morbidity and mortality, and thromboprophylaxis is indicated in pregnant and post-partum women with a history of venous thromboembolism. The optimal dose of low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy and the post-partum period is uncertain. METHODS: In this open-label, randomised, controlled trial (Highlow), pregnant women with a history of venous thromboembolism were recruited from 70 hospitals in nine countries (the Netherlands, France, Ireland, Belgium, Norway, Denmark, Canada, the USA, and Russia). Women were eligible if they were aged 18 years or older with a history of objectively confirmed venous thromboembolism, and with a gestational age of 14 weeks or less. Eligible women were randomly assigned (1:1), before 14 weeks of gestational age, using a web-based system and permuted block randomisation (block size of six), stratified by centre, to either weight-adjusted intermediate-dose or fixed low-dose low-molecular-weight heparin subcutaneously once daily until 6 weeks post partum. The primary efficacy outcome was objectively confirmed venous thromboembolism (ie, deep-vein thrombosis, pulmonary embolism, or unusual site venous thrombosis), as determined by an independent central adjudication committee, in the intention-to-treat (ITT) population (ie, all women randomly assigned to treatment). The primary safety outcome was major bleeding which included antepartum, early post-partum (within 24 h after delivery), and late post-partum major bleeding (24 h or longer after delivery until 6 weeks post partum), assessed in all women who received at least one dose of assigned treatment and had a known end of treatment date. This study is registered with ClinicalTrials.gov, NCT01828697, and is now complete. FINDINGS: Between April 24, 2013, and Oct 31, 2020, 1339 pregnant women were screened for eligibility, of whom 1110 were randomly assigned to weight-adjusted intermediate-dose (n=555) or fixed low-dose (n=555) low-molecular-weight heparin (ITT population). Venous thromboembolism occurred in 11 (2%) of 555 women in the weight-adjusted intermediate-dose group and in 16 (3%) of 555 in the fixed low-dose group (relative risk [RR] 0·69 [95% CI 0·32-1·47]; p=0·33). Venous thromboembolism occurred antepartum in five (1%) women in the intermediate-dose group and in five (1%) women in the low-dose group, and post partum in six (1%) women and 11 (2%) women. On-treatment major bleeding in the safety population (N=1045) occurred in 23 (4%) of 520 women in the intermediate-dose group and in 20 (4%) of 525 in the low-dose group (RR 1·16 [95% CI 0·65-2·09]). INTERPRETATION: In women with a history of venous thromboembolism, weight-adjusted intermediate-dose low-molecular-weight heparin during the combined antepartum and post-partum periods was not associated with a lower risk of recurrence than fixed low-dose low-molecular-weight heparin. These results indicate that low-dose low-molecular-weight heparin for thromboprophylaxis during pregnancy is the appropriate dose for the prevention of pregnancy-related recurrent venous thromboembolism. FUNDING: French Ministry of Health, Health Research Board Ireland, GSK/Aspen, and Pfizer.

Vitamin E in Cancer Treatment: A Review of Clinical Applications in Randomized Control Trials.

Vitamin E, along with other vitamins and micronutrients play a range of physiologic roles in the homeostasis of the body. Moreover, they also have postulated therapeutic roles that are often incompletely studied and understood. In this scoping review, we explored the recent randomized control trials (RCTs) of Vitamin E in the context of cancer, to investigate whether Vitamin E has a therapeutic role. We searched major bibliographic electronic databases to identify sixteen RCTs studying the role of Vitamin E in cancer management that have been published in the last ten years. These studies had different methodological qualities, including some that used Vitamin E in combination with other treatments. Furthermore, due to the heterogenous results, it is difficult to make a consensus statement on the effectiveness of Vitamin E in cancer therapeutics. In some cases, there were even suggestion of detriment with Vitamin E supplementation. Therefore, well designed, large, prospective RCTs are needed studying pure isoforms of Vitamin E to establish the safety and efficacy of this dietary supplement.

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.

Management of pregnancy in a patient with long-chain 3-hydroxyacyl CoA dehydrogenase deficiency.

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare mitochondrial defect of ß-oxidation of long-chain fatty acids. Patients may present with muscle pain, hypotonia, peripheral neuropathy, cardiomyopathy, recurrent rhabdomyolysis and sudden death. Dietary management of LCHADD aims at preventing prolonged fasting and decreasing energy production from long-chain fatty acids compensated by an increase in medium-chain triglyceride fat. Herein, we present medical and dietetic management of a successful pregnancy in a LCHADD female patient and the delivery of a healthy baby boy.

Exploring the barriers and enablers experienced by people with Cystic Fibrosis and their healthcare professionals in accessing, utilising and delivering maternity and Cystic Fibrosis care during the pre-conception to post-partum period: A mixed methods systematic review protocol.

Background Cystic Fibrosis (CF) is an autosomal recessive inherited multi-system disease that primarily affects the lungs and digestive system. New drug therapies and treatments are improving the lives of many people with CF. With improved life expectancy and increased quality of life, many people with CF are now contemplating parenthood and becoming pregnant, an aspiration that decades ago was almost unheard of. Given this quickly evolving and more positive health landscape, it is vital to understand how people with CF experience the care they receive whilst accessing and utilising fertility and maternity services. It is also important to explore the experiences of healthcare professionals involved in providing care during this period. The overall aim of the mixed-methods systematic review will be to explore the barriers and enablers experienced by people with CF and the healthcare professionals involved in their care in the pre-conception to post-partum period. Methods The proposed review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for convergent integrated mixed methods systematic reviews. A systematic search of Medline (Ebsco), Cinahl, Embase, APA PsychINFO and Cochrane Library from inception to February 2022 will be conducted. Quantitative, qualitative and mixed methods studies pertaining to the experience of pre-conception to post-partum care for people with CF and their healthcare professionals will be included. Two independent reviewers will screen titles, abstracts and full texts with disagreements being resolved by a third reviewer. Conclusion This review will help to determine the potential barriers and facilitators experienced by people with Cystic Fibrosis and the health care professionals involved in their care during the pre-conception to post-partum period. The results will be of benefit specifically to the CF population and their healthcare providers when planning further studies in the area of fertility and pregnancy for this population and when delivering care.