Search

Purpose: To investigate the utility of umbilical artery (UA) lactate measurements in a South African hospital for assessing intrapartum care and predicting neonatal outcomes.Materials and Methods: From 3 March-12 November 2014, we conducted a prospective cohort study of UA lactate levels at Kalafong Hospital, Pretoria, South Africa. Following birth, a UA blood sample (<0.5uL) was taken from a double-clamped segment of cord and the lactate measured. Maternal and neonatal characteristics and outcomes were recorded.Results: During the study, there were 4668 deliveries; including 1091 emergency cesarean and 154 instrumental deliveries. A lactate was recorded for 946 deliveries (20.3%). 190 babies required neonatal resuscitation, with an optimal cutoff for lactate of 5.45 mmol/L (sensitivity 68%, specificity 72%). 124 babies required nursery admission with the optimal cutoff for lactate 4.95 mmol/L (sensitivity 61%, specificity 59%). 55 babies had an Apgar score <7 at 5 min and the optimal lactate for this outcome was 5.65 mmol/L (sensitivity 64%, specificity of 69%).Conclusions: Umbilical lactate can be used in a middle-low resource setting as a measurement of intrapartum hypoxia, with reasonable sensitivity and specificity for the prediction of, or need for, resuscitation, admission to the nursery, and low Apgar scores. [ABSTRACT FROM AUTHOR]

Background: Umbilical cord lactate is one approach to measuring acidosis and intrapartum hypoxia, knowledge of which may be helpful for clinicians involved in the care of women and newborns.Objective: To synthesise the evidence on accuracy of umbilical cord lactate in measuring acidosis and predicting poor neonatal outcome.Search Strategy: Studies published and unpublished between 1990 and 2014 from PubMed/Medline, EMBASE, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov were assessed.Selection Criteria: Cross-sectional and randomised studies that assessed fetal acidosis (using lactate as the index test) with or without an assessment of neonatal outcome.Data Collection and Analysis: Correlations between index and reference test(s) were recorded, as were the raw data to classify the predictive ability of umbilical lactate for neonatal outcomes. Meta-analysis of correlation was performed. We plotted estimates of the studies' observed sensitivities and specificities on Forest plots with 95% confidence intervals (CI). Where possible, we combined data using meta-analysis, applying the hierarchical summary receiver operating characteristics model and a bivariate model.Main Results: Twelve studies were included. Umbilical lactate correlated with pH [pooled effect size (ES) -0.650; 95% CI -0.663 to -0.637, P < 0.001], base excess (ES -0.710; 95% CI -0.721 to -0.699, P < 0.001), and Apgar scores at 5 minutes (ES 0.300; 95% 0.193-0.407, P < 0.001). Umbilical lactate had pooled sensitivity and specificity for predicting neonatal neurological outcome including hypoxic ischaemic encephalopathy of 69.7% (95% CI 23.8-94.4%) and 93% (95% CI 86.8-96.3%).Authors' Conclusion: Umbilical cord lactate is a clinically applicable, inexpensive and effective way to measure acidosis and is a tool that may be used in the assessment of neonatal outcome.Tweetable Abstract: Umbilical cord lactate: a clinically applicable, inexpensive, effective way to measure intrapartum acidosis. [ABSTRACT FROM AUTHOR]

The article discusses the ICD-PM perinatal period deaths classification being developed by the World Health Organization based on existing International Classification of Diseases-10 (ICD-10) codes. Topics include reference to unrecognized stillbirths or neonatal deaths, unifying perinatal death classification system with the contributing maternal factors as well as convened groups of experts such as obstetricians and neonatologists. Also mentioned are ICD-MM codes and the epidemiologists.

Objective: To apply the World Health Organization (WHO) Application of the International Classification of Diseases, tenth revision (ICD-10) to deaths during the perinatal period: ICD-Perinatal Mortality (ICD-PM) to existing perinatal death databases.Design: Retrospective application of ICD-PM.Setting: South Africa, UK.Population: Perinatal death databases.Methods: Deaths were grouped according to timing of death and then by the ICD-PM cause of death. The main maternal condition at the time of perinatal death was assigned to each case.Main Outcome Measures: Causes of perinatal mortality, associated maternal conditions.Results: In South Africa 344/689 (50%) deaths occurred antepartum, 11% (n = 74) intrapartum and 39% (n = 271) in the early neonatal period. In the UK 4377/9067 (48.3%) deaths occurred antepartum, with 457 (5%) intrapartum and 4233 (46.7%) in the neonatal period. Antepartum deaths were due to unspecified causes (59%), chromosomal abnormalities (21%) or problems related to fetal growth (14%). Intrapartum deaths followed acute intrapartum events (69%); neonatal deaths followed consequences of low birthweight/ prematurity (31%), chromosomal abnormalities (26%), or unspecified causes in healthy mothers (25%). Mothers were often healthy; 53%, 38% and 45% in the antepartum, intrapartum and neonatal death groups, respectively. Where there was a maternal condition, it was most often maternal medical conditions, and complications of placenta, cord and membranes.Conclusions: The ICD-PM can be a globally applicable perinatal death classification system that emphasises the need for a focus on the mother-baby dyad as we move beyond 2015.Tweetable Abstract: ICD-PM is a global system that classifies perinatal deaths and links them to maternal conditions. [ABSTRACT FROM AUTHOR]

Objective: We explore preterm-related neonatal deaths using the WHO application of the International Classification of Disease (ICD-10) to deaths during the perinatal period: ICD-PM as an informative case study, where ICD-PM can improve data use to guide clinical practice and programmatic decision-making.Design: Retrospective application of ICD-PM.Setting: South Africa, and the UK.Population: Perinatal death databases.Methods: Descriptive analysis of neonatal deaths and maternal conditions present.Main Outcome Measures: Causes of preterm neonatal mortality and associated maternal conditions.Results: We included 98 term and 173 preterm early neonatal deaths from South Africa, and 956 term and 3248 preterm neonatal deaths from the UK. In the South African data set, the main causes of death were respiratory/cardiovascular disorders (34.7%), low birthweight/prematurity (29.2%), and disorders of cerebral status (25.5%). Amongst preterm deaths, low birthweight/prematurity (43.9%) and respiratory/cardiovascular disorders (32.4%) were the leading causes. In the data set from the UK, the leading causes of death were low birthweight/prematurity (31.6%), congenital abnormalities (27.4%), and deaths of unspecified cause (26.1%). In the preterm deaths, the leading causes were low birthweight/prematurity (40.9%) and deaths of unspecified cause (29.6%). In South Africa, 61% of preterm deaths resulted from the maternal condition of preterm spontaneous labour. Among the preterm deaths in the data set from the UK, no maternal condition was present in 36%, followed by complications of placenta, cord, and membranes (23%), and other complications of labour and delivery (22%).Conclusions: ICD-PM can be used to appraise the maternal and newborn conditions contributing to preterm deaths, and can inform practice.Tweetable Abstract: ICD-PM can be used to appraise maternal and newborn contributors to preterm deaths to improve quality of care. [ABSTRACT FROM AUTHOR]

Objective: The WHO application of the tenth edition of the International Classification of Diseases (ICD-10) to deaths during the perinatal period (ICD Perinatal Mortality, ICD-PM) captures the essential characteristics of the mother-baby dyad that contribute to perinatal deaths. We compare the capture of maternal conditions in the existing ICD-PM with the maternal codes from the WHO application of ICD-10 to deaths during pregnancy, childbirth, and the puerperium (ICD Maternal Mortality, ICD-MM) to explore potential benefits in the quality of data received.Design: Retrospective application of ICD-PM.Setting: South Africa and the UK.Population: Perinatal death databases.Methods: The maternal conditions were classified using the ICD-PM groupings for maternal condition in perinatal death, and then mapped to the ICD-MM groupings of maternal conditions.Main Outcome Measures: Main maternal conditions in perinatal deaths.Results: We reviewed 9661 perinatal deaths. The largest group (4766 cases, 49.3%) in both classifications captures deaths where there was no contributing maternal condition. Each of the other ICD-PM groups map to between three and six ICD-MM groups. If the cases in each ICD-PM group are re-coded using ICD-MM, each group becomes multiple, more specific groups. For example, the 712 cases in group M4 in ICD-PM become 14 different and more specific main disease categories when the ICD-MM is applied instead.Conclusions: As we move towards ICD-11, the use of the more specific, applicable, and relevant codes outlined in ICD-MM for both maternal deaths and the maternal condition at the time of a perinatal death would be preferable, and would provide important additional information about perinatal deaths.Tweetable Abstract: Improving the capture of maternal conditions in perinatal deaths provides important actionable information. [ABSTRACT FROM AUTHOR]

The Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Consensus Conference on Clinical Research (ECCC) was held in Incheon, South Korea, Nov 2-3, 2023. The aims were to develop consensus statements for future trials in endometrial cancer to achieve harmonisation on design elements, select important questions, and identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and finalisation of 18 statements within four topic groups, addressing adjuvant treatment in high-risk disease; treatment for metastatic and recurrent disease; trial designs for rare endometrial cancer subgroups and special circumstances; and specific methodology and adaptation for trials in low-resource settings. In addition, eight areas of unmet need were identified. This was the first GCIG Consensus Conference to include patient advocates and an expert on inclusion, diversity, equity, and access to take part in all aspects of the process and output. Four early-career investigators were also selected for participation, ensuring that they represented different GCIG member groups and regions. Unanimous consensus was obtained for 16 of the 18 statements, with 97% concordance for the remaining two. Using the described methodology from previous Ovarian Cancer Consensus Conferences, this conference did not require even one minority statement. The high acceptance rate following active involvement in the preparation, discussion, and refinement of the statements by all representatives confirmed the consensus progress within a global academic setting, and the expectation that the ECCC will lead to greater harmonisation, actualisation, inclusion, and resolution of unmet needs in clinical research for individuals living with and beyond endometrial cancer worldwide., Competing Interests: Declaration of interests All authors report that the KGOG paid for their 2-night hotel stay and basic meals during the 2 days of the ECCC on Clinical Research meeting. CLC reports a research grant paid to her institution from Varian; payment to her institution for participation on a data safety monitoring board from Merck; and unpaid roles as chair of GCIG Endometrial Committee and member of Guidelines Committees for Endometrial cancer of the European Society of Gynaecologic Oncology (ESGO) and the European Society of Radiotherapy and Oncology. GE reports personal consulting fees from MSD, personal fees from Eisai, and support for attending a meeting or travel from MSD. LE reports personal consulting fees AstraZeneca, GSK, and MSD; personal fees from AstraZeneca and GSK, and support for attending a meeting or travel from AstraZeneca and GSK. RAN reports research grants paid to his institution from Elekta, Varian, and Accuray; and payment to his institution for presentations from Elekta and MSD. DL reports research grants both personal and paid to her institution from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, Novartis, Pharmamar, and Seagen; personal grants from Corcept, Oncoinvest, and Sutro; and grants to her institution from Incyte and Roche; consulting fees from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Pharmamar, Seagen, and Sutro; payment for presentations from Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Pharmamar, Seagen, and Sutro; support for attending a meeting or travel from AstraZeneca, Clovis Oncology, MSD and GSK; and payments for participation on a data safety monitoring board from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Pharmamar, Seagen, and Sutro. AO reports research grants paid to his institution from AstraZeneca; consulting fees from Bristol Myers Squibb, uncompensated participation on data and safety monitoring boards of studies funded by AstraZeneca and GlaxoSmithKline; and unpaid roles as principal investigator on investigator-initiated trials and on steering committees of trials funded by AstraZeneca and GlaxoSmithKline. BP reports research grants from Tesaro/GSK, Merck, AstraZeneca, Karyopharm Therapeutics, Sutro, Incyte, Clovis Oncology, Roche/Genentech, Mersana, Celsion/Immunon, Imab, Takeda, Toray, VBL Therapeutics, InxMed, Agenus, Seagen, NRG Oncology, Duality Bio, Xencor, Onconova, Celgene, Sutro Biopharma, Novocure, Immunogen, Eisai, Acrivon, and Alkermes; consulting fees from Tesaro/GSK, AstraZeneca, Merck, Immunogen, Gynecologic Oncology Group (GOG) Foundation, SeaGen, Lily, Eisai, Signatera, Celsion, Butro Biopharma, Imvax, Incyte, InxMed, Onconova Therapeutics, R Pharm, Regeneron, and Duality Bio; payment for presentations from Bioascend, PERS, Vanium, Curio, OncLive, Yale University and PeerView; support for attending a meeting or travel from GOG Partners, payment for participation on a data safety monitoring board or advisory board from Sutro, AstraZeneca, GOG Foundation, Celsion/Immunon, Toray, InxMed, Imvax, Imab, Tesaro/GSK, Merck, Mersana, Nuvation, and BioNtech; and unpaid leadership roles in boards, societies and committees: Society of Gynecologic Oncology (SGO) Clinical Practice Committee Chair, SGO Board of Directors, SGO COVID-19 Taskforce co-chair, GOG Partners, and New York Obstetrical Society Second VP. BH reports textbook royalties from Elsevier; consulting fees from Tempus; honoraria for lectures from Leica and Projects in Knowledge; and unpaid leadership roles on the International Society of Gynecological Pathologists Board of Directors (as member at large) and on the Endometrial Cancer MSI Committee of the College of American Pathologists. IR-C reports research grants from AstraZeneca, Clovis, GSK, Mersana, BMS, and MSD; payment for presentations from AstraZeneca, Clovis, GSK, Mersana, BMS, MSD, Roche, Pharmamar, Seagen, Eisai, and Novartis; support for attending a meeting or travel from Roche, GSK, AstraZeneca, Pharmamar, and MSD; and payment for participation on a data safety monitoring board or advisory board from Clovis, Deciphera, Adaptimmue, Sutro, and Immunogen. DG reports support for attending meetings or travel from IGCS Board of Directors; payment for participation on a data and safety monitoring board from Merck, and a leadership role in NRG Oncology. AM reports payment for participation as independent statistician on data safety monitoring boards from ONY Biotech, Regeneron, and Genentech/Roche. NC reports payments or honoraria for presentations from GSK, Seagen, Akesobio, AstraZeneca, eTheRNA immunotherapies NV, Kartos, MSD, Mersana, ImmunoGen, Eisai, Seattle Genetics, TouchIME, and Medscape Oncology; support for attending a meeting or travel from Roche, Genmab, and Amgen; payment for participation on a data safety monitoring board or advisory board from GSK, Mersana, Seagen, ImmunoGen, Akesobio, Eisai, AstraZeneca, Mersana, Seattle Genetics, eTheRNA immunotherapies NV, and Kartos; and leadership roles as President of ESGO and Chair of European Network for Gynaecological Oncological Trial groups Early Drug Development Network. MAP reports grants paid to his institution from GSK; payment for participation on a data and safety monitoring board from GSK, AstraZeneca, Eisai, Merck, Immunogen, Clovis Oncology, Jazz Pharma, and SeaGen; and payment to his institution for a leadership role on a board or committee from NRG Oncology. MAB reports payment to his institution for participation on a data and safety monitoring board from Immunogen; and employment as physician at The Permanente Medical Group. J-WK, EA, SIK, J-YP, LM, PBO, AB, DM, VG, TB, CG, TM, HW, XM-G, WS, and GS declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Surgical decision making is complex and involves a combination of analytic, intuitive, and cognitive processes. Medicolegal, infrastructural, and financial factors may influence these processes depending on the context and setting, but to what extent can they influence surgical decision making in gynecologic oncology? This scoping review evaluates existing literature related to medicolegal, infrastructural, and financial aspects of gynecologic cancer surgery and their implications in surgical decision making. Our objective was to summarize the findings and limitations of published research, identify gaps in the literature, and make recommendations for future research to inform policy., Competing Interests: Competing interests: PAC declares honoraria from Astra Zeneca unrelated to the submitted work., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To meet the demand for cervical cancer care in Africa, access to surgical and radiation therapy services needs to be understood. We thus mapped the availability of gynecologic and radiation therapy equipment and staffing for treating cervical cancer., Methods and Materials: We collected data on gynecologic and radiation oncology staffing, equipment, and infrastructure capacities across Africa. Data was obtained from February to July 2021 through collaboration with international partners using Research Electronic Data Capture. Cancer incidence was taken from the International Agency for Research on Cancer's GLOBOCAN 2020 database. Treatment capacity, including the numbers of radiation oncologists, radiation therapists, physicists, gynecologic oncologists, and hospitals performing gynecologic surgeries, was calculated per 1000 cervical cancer cases. Adequate capacity was defined as 2 radiation oncologists and 2 gynecologic oncologists per 1000 cervical cancer cases., Results: Forty-three of 54 African countries (79.6%) responded, and data were not reported for 11 countries (20.4%). Respondents from 31 countries (57.4%) reported access to specialist gynecologic oncology services, but staffing was adequate in only 11 countries (20.4%). Six countries (11%) reported that generalist obstetrician-gynecologists perform radical hysterectomies. Radiation oncologist access was available in 39 countries (72.2%), but staffing was adequate in only 16 countries (29.6%). Six countries (11%) had adequate staffing for both gynecologic and radiation oncology; 7 countries (13%) had no radiation or gynecologic oncologists. Access to external beam radiation therapy was available in 31 countries (57.4%), and access to brachytherapy was available in 25 countries (46.3%). The number of countries with training programs in gynecologic oncology, radiation oncology, medical physics, and radiation therapy were 14 (26%), 16 (30%), 11 (20%), and 17 (31%), respectively., Conclusions: We identified areas needing comprehensive cervical cancer care infrastructure, human resources, and training programs. There are major gaps in access to radiation oncologists and trained gynecologic oncologists in Africa., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Ensuring timely follow-up of abnormal screening results is essential for eliminating cervical cancer., Objective: The purpose of the study was to review single and multicomponent interventions designed to improve follow-up of women with abnormal cervical cancer screening results. We report on effectiveness across studies, and describe what aspects of these interventions might be more impactful., Methods: Publications were searched between January 2000 and December 2022. The search included observational, quasi-experimental (pre-post studies) and randomized controlled studies describing at least one intervention to increase follow-up of women with abnormal cervical cancer screening results. Outcomes of studies included completion of any follow-up (i.e., attending a follow-up appointment), timely diagnosis (i.e., colposcopy results within 90 days of screening) and time to diagnostic resolution (i.e., days between screening and final diagnosis). We assessed risk of bias for observational and quasi-experimental studies using the Newcastle-Ottawa Scale (NOS) tool and the Cochrane collaboration tool for randomized studies. We conducted a meta-analysis using studies where data were provided to estimate a summary average effect of the interventions on follow-up of patients and to identify characteristics of studies associated with an increased effectiveness of interventions. We extracted the comparison and intervention proportions of women with follow-up before and after the intervention (control and intervention) and plotted the odds ratios (ORs) of completing follow-up along with the 95% confidence intervals (CIs) using forest plots for the interventions vs. controls when data were available., Findings: From 7,457 identified studies, 28 met the inclusion criteria. Eleven (39%) of the included studies had used a randomized design. Most studies (63%) assessed completion of any follow-up visit as the primary outcome, whereas others measured time to definite diagnosis (15%) or diagnostic resolution (22%). Navigation was used as a type of intervention in 63% of the included studies. Most interventions utilized behavioral approaches to improve outcomes. The overall estimate of the OR for completion of follow-up for all interventions was 1.81 (1.36-2.42). The highest impact was for programs using more than one approach (multicomponent interventions) to improve outcomes with OR = 3.01 (2.03-4.46), compared with studies with single intervention approaches with OR = 1.56 (1.14-2.14). No statistical risks were noted from publication bias or small-study effects in the studies reviewed., Conclusion: Our findings revealed large heterogeneity in how follow-up of abnormal cervical cancer screening results was defined. Our results suggest that multicomponent interventions were more effective than single component interventions and should be used to improve follow-up after abnormal cervical cancer screening results. Navigation appears to be an important tool for improving follow-up. We also provide recommendations for future studies and implications for policy in terms of better defining outcomes for these interventions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Varon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Current guidelines recommend that resolution of a complete molar pregnancy (CMP) can only be confirmed once a negative β-human chorionic gonadotropin (β-hCG) has been maintained for six months following uterine surgical evacuation. However, multiple studies have found that the risk of developing gestational trophoblastic neoplasia (GTN) once a negative β-hCG had been obtained is negligible, which suggests that a shorter follow-up may be reasonable., Aim: To determine the trend in β-hCG following diagnosis of a CMP and the incidence of GTN, in a single unit., Materials and Methods: All patients presenting to the tertiary hospital, Royal Prince Alfred Hospital Early Pregnancy Assessment Service (RPAH EPAS), with a histopathological diagnosis of a CMP between 2010 and 2017 were included. Data collected included age, parity, β-hCG at diagnosis, subsequent β-hCG levels, incidence of GTN and treatment required., Results: Sixty-seven patients were diagnosed with CMP between January 2010 and July 2017 through RPAH EPAS. The mean age of women diagnosed with a CMP was 33 years. None of the 40 patients who spontaneously achieved a negative β-hCG and completed their six months follow-up had a subsequent rise in β-hCG. The median number of days from surgical evacuation to normalisation of β-hCG was 55.5 days. Sixteen out of 67 patients who had a CMP required further management for persistent GTN. None of these patients achieved a negative β-hCG prior to further management., Conclusions: Consideration could be made to decreasing the period of β-hCG monitoring for women who achieve a spontaneous negative β-hCG following surgical evacuation of a CMP., (© 2020 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Stillbirths and neonatal deaths have long been imperfectly classified and recorded worldwide. In Hong Kong, the current code system is deficient (>90% cases with unknown causes) in providing the diagnoses of perinatal mortality cases., Objective: The objective of this study was to apply the International Classification of Diseases for Perinatal Mortality (ICD-PM) system to existing perinatal death data. Further, the aim was to assess whether there was any change in the classifications of perinatal deaths compared with the existing classification system and identify any areas in which future interventions can be made., Methods: We applied the ICD-PM (with International Statistical Classification of Diseases and Related Health Problems, 10th Revision) code system to existing perinatal death data in Kwong Wah Hospital, Hong Kong, to improve diagnostic classification. The study included stillbirths (after 24 weeks gestation) and neonatal deaths (from birth to 28 days). The retrospective data (5 years) from May 1, 2012, to April 30, 2017, were recoded by the principal investigator (HML) applying the ICD-PM, then validated by an overseas expert (EA) after she reviewed the detailed case summaries. The prospective application of ICD-PM from May 1, 2017, to April 30, 2019, was performed during the monthly multidisciplinary perinatal meetings and then also validated by EA for agreement., Results: We analyzed the data of 34,920 deliveries, and 119 cases were included for analysis (92 stillbirths and 27 neonatal deaths). The overall agreement with EA of our codes using the ICD-PM was 93.2% (111/119); 92% (78/85) for the 5 years of retrospective codes and 97% (33/34) for the 2 years of prospective codes (P=.44). After the application of the ICD-PM, the overall proportion of unknown causes of perinatal mortality dropped from 34.5% (41/119) to 10.1% (12/119) of cases (P<.001)., Conclusions: Using the ICD-PM would lead to a better classification of perinatal deaths, reduce the proportion of unknown diagnoses, and clearly link the maternal conditions with these perinatal deaths., (©Hiu Mei Luk, Emma Allanson, Wai-Kit Ming, Wing Cheong Leung. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 03.08.2020.)

Background: The number of de novo genome sequence assemblies is increasing exponentially; however, relatively few contain one scaffold/contig per chromosome. Such assemblies are essential for studies of genotype-to-phenotype association, gross genomic evolution, and speciation. Inter-species differences can arise from chromosomal changes fixed during evolution, and we previously hypothesized that a higher fraction of elements under negative selection contributed to avian-specific phenotypes and avian genome organization stability. The objective of this study is to generate chromosome-level assemblies of three avian species (saker falcon, budgerigar, and ostrich) previously reported as karyotypically rearranged compared to most birds. We also test the hypothesis that the density of conserved non-coding elements is associated with the positions of evolutionary breakpoint regions., Results: We used reference-assisted chromosome assembly, PCR, and lab-based molecular approaches, to generate chromosome-level assemblies of the three species. We mapped inter- and intrachromosomal changes from the avian ancestor, finding no interchromosomal rearrangements in the ostrich genome, despite it being previously described as chromosomally rearranged. We found that the average density of conserved non-coding elements in evolutionary breakpoint regions is significantly reduced. Fission evolutionary breakpoint regions have the lowest conserved non-coding element density, and intrachromomosomal evolutionary breakpoint regions have the highest., Conclusions: The tools used here can generate inexpensive, efficient chromosome-level assemblies, with > 80% assigned to chromosomes, which is comparable to genomes assembled using high-density physical or genetic mapping. Moreover, conserved non-coding elements are important factors in defining where rearrangements, especially interchromosomal, are fixed during evolution without deleterious effects.

Background: Stillbirth is a global health problem. The World Health Organization (WHO) application of the International Classification of Diseases for perinatal mortality (ICD-PM) aims to improve data on stillbirth to enable prevention., Objectives: To identify globally reported causes of stillbirth, classification systems, and alignment with the ICD-PM., Search Strategy: We searched CINAHL, EMBASE, Medline, Global Health, and Pubmed from 2009 to 2016., Selection Criteria: Reports of stillbirth causes in unselective cohorts., Data Collection and Analysis: Pooled estimates of causes were derived for country representative reports. Systems and causes were assessed for alignment with the ICD-PM. Data are presented by income setting (low, middle, and high income countries; LIC, MIC, HIC)., Main Results: Eighty-five reports from 50 countries (489 089 stillbirths) were included. The most frequent categories were Unexplained, Antepartum haemorrhage, and Other (all settings); Infection and Hypoxic peripartum (LIC), and Placental (MIC, HIC). Overall report quality was low. Only one classification system fully aligned with ICD-PM. All stillbirth causes mapped to ICD-PM. In a subset from HIC, mapping obscured major causes., Conclusions: There is a paucity of quality information on causes of stillbirth globally. Improving investigation of stillbirths and standardisation of audit and classification is urgently needed and should be achievable in all well-resourced settings. Implementation of the WHO Perinatal Mortality Audit and Review guide is needed, particularly across high burden settings., Funding: HR, SH, SHL, and AW were supported by an NHMRC-CRE grant (APP1116640). VF was funded by an NHMRC-CDF (APP1123611)., Tweetable Abstract: Urgent need to improve data on causes of stillbirths across all settings to meet global targets., Plain Language Summary: Background and methods Nearly three million babies are stillborn every year. These deaths have deep and long-lasting effects on parents, healthcare providers, and the society. One of the major challenges to preventing stillbirths is the lack of information about why they happen. In this study, we collected reports on the causes of stillbirth from high-, middle-, and low-income countries to: (1) Understand the causes of stillbirth, and (2) Understand how to improve reporting of stillbirths. Findings We found 85 reports from 50 different countries. The information available from the reports was inconsistent and often of poor quality, so it was hard to get a clear picture about what are the causes of stillbirth across the world. Many different definitions of stillbirth were used. There was also wide variation in what investigations of the mother and baby were undertaken to identify the cause of stillbirth. Stillbirths in all income settings (low-, middle-, and high-income countries) were most frequently reported as Unexplained, Other, and Haemorrhage (bleeding). Unexplained and Other are not helpful in understanding why a baby was stillborn. In low-income countries, stillbirths were often attributed to Infection and Complications during labour and birth. In middle- and high-income countries, stillbirths were often reported as Placental complications. Limitations We may have missed some reports as searches were carried out in English only. The available reports were of poor quality. Implications Many countries, particularly those where the majority of stillbirths occur, do not report any information about these deaths. Where there are reports, the quality is often poor. It is important to improve the investigation and reporting of stillbirth using a standardised system so that policy makers and healthcare workers can develop effective stillbirth prevention programs. All stillbirths should be investigated and reported in line with the World Health Organization standards., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Background: Umbilical cord lactate is one approach to measuring acidosis and intrapartum hypoxia, knowledge of which may be helpful for clinicians involved in the care of women and newborns., Objective: To synthesise the evidence on accuracy of umbilical cord lactate in measuring acidosis and predicting poor neonatal outcome., Search Strategy: Studies published and unpublished between 1990 and 2014 from PubMed/Medline, EMBASE, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov were assessed., Selection Criteria: Cross-sectional and randomised studies that assessed fetal acidosis (using lactate as the index test) with or without an assessment of neonatal outcome., Data Collection and Analysis: Correlations between index and reference test(s) were recorded, as were the raw data to classify the predictive ability of umbilical lactate for neonatal outcomes. Meta-analysis of correlation was performed. We plotted estimates of the studies' observed sensitivities and specificities on Forest plots with 95% confidence intervals (CI). Where possible, we combined data using meta-analysis, applying the hierarchical summary receiver operating characteristics model and a bivariate model., Main Results: Twelve studies were included. Umbilical lactate correlated with pH [pooled effect size (ES) -0.650; 95% CI -0.663 to -0.637, P < 0.001], base excess (ES -0.710; 95% CI -0.721 to -0.699, P < 0.001), and Apgar scores at 5 minutes (ES 0.300; 95% 0.193-0.407, P < 0.001). Umbilical lactate had pooled sensitivity and specificity for predicting neonatal neurological outcome including hypoxic ischaemic encephalopathy of 69.7% (95% CI 23.8-94.4%) and 93% (95% CI 86.8-96.3%)., Authors' Conclusion: Umbilical cord lactate is a clinically applicable, inexpensive and effective way to measure acidosis and is a tool that may be used in the assessment of neonatal outcome., Tweetable Abstract: Umbilical cord lactate: a clinically applicable, inexpensive, effective way to measure intrapartum acidosis., (© 2016 Royal College of Obstetricians and Gynaecologists.)

Objective: We explore preterm-related neonatal deaths using the WHO application of the International Classification of Disease (ICD-10) to deaths during the perinatal period: ICD-PM as an informative case study, where ICD-PM can improve data use to guide clinical practice and programmatic decision-making., Design: Retrospective application of ICD-PM., Setting: South Africa, and the UK., Population: Perinatal death databases., Methods: Descriptive analysis of neonatal deaths and maternal conditions present., Main Outcome Measures: Causes of preterm neonatal mortality and associated maternal conditions., Results: We included 98 term and 173 preterm early neonatal deaths from South Africa, and 956 term and 3248 preterm neonatal deaths from the UK. In the South African data set, the main causes of death were respiratory/cardiovascular disorders (34.7%), low birthweight/prematurity (29.2%), and disorders of cerebral status (25.5%). Amongst preterm deaths, low birthweight/prematurity (43.9%) and respiratory/cardiovascular disorders (32.4%) were the leading causes. In the data set from the UK, the leading causes of death were low birthweight/prematurity (31.6%), congenital abnormalities (27.4%), and deaths of unspecified cause (26.1%). In the preterm deaths, the leading causes were low birthweight/prematurity (40.9%) and deaths of unspecified cause (29.6%). In South Africa, 61% of preterm deaths resulted from the maternal condition of preterm spontaneous labour. Among the preterm deaths in the data set from the UK, no maternal condition was present in 36%, followed by complications of placenta, cord, and membranes (23%), and other complications of labour and delivery (22%)., Conclusions: ICD-PM can be used to appraise the maternal and newborn conditions contributing to preterm deaths, and can inform practice., Tweetable Abstract: ICD-PM can be used to appraise maternal and newborn contributors to preterm deaths to improve quality of care., (© 2016 Royal College of Obstetricians and Gynaecologists The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Objective: The WHO application of the tenth edition of the International Classification of Diseases (ICD-10) to deaths during the perinatal period (ICD Perinatal Mortality, ICD-PM) captures the essential characteristics of the mother-baby dyad that contribute to perinatal deaths. We compare the capture of maternal conditions in the existing ICD-PM with the maternal codes from the WHO application of ICD-10 to deaths during pregnancy, childbirth, and the puerperium (ICD Maternal Mortality, ICD-MM) to explore potential benefits in the quality of data received., Design: Retrospective application of ICD-PM., Setting: South Africa and the UK., Population: Perinatal death databases., Methods: The maternal conditions were classified using the ICD-PM groupings for maternal condition in perinatal death, and then mapped to the ICD-MM groupings of maternal conditions., Main Outcome Measures: Main maternal conditions in perinatal deaths., Results: We reviewed 9661 perinatal deaths. The largest group (4766 cases, 49.3%) in both classifications captures deaths where there was no contributing maternal condition. Each of the other ICD-PM groups map to between three and six ICD-MM groups. If the cases in each ICD-PM group are re-coded using ICD-MM, each group becomes multiple, more specific groups. For example, the 712 cases in group M4 in ICD-PM become 14 different and more specific main disease categories when the ICD-MM is applied instead., Conclusions: As we move towards ICD-11, the use of the more specific, applicable, and relevant codes outlined in ICD-MM for both maternal deaths and the maternal condition at the time of a perinatal death would be preferable, and would provide important additional information about perinatal deaths., Tweetable Abstract: Improving the capture of maternal conditions in perinatal deaths provides important actionable information., (© 2016 Royal College of Obstetricians and Gynaecologists The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Objective: To apply the World Health Organization (WHO) Application of the International Classification of Diseases, tenth revision (ICD-10) to deaths during the perinatal period: ICD-Perinatal Mortality (ICD-PM) to existing perinatal death databases., Design: Retrospective application of ICD-PM., Setting: South Africa, UK., Population: Perinatal death databases., Methods: Deaths were grouped according to timing of death and then by the ICD-PM cause of death. The main maternal condition at the time of perinatal death was assigned to each case., Main Outcome Measures: Causes of perinatal mortality, associated maternal conditions., Results: In South Africa 344/689 (50%) deaths occurred antepartum, 11% (n = 74) intrapartum and 39% (n = 271) in the early neonatal period. In the UK 4377/9067 (48.3%) deaths occurred antepartum, with 457 (5%) intrapartum and 4233 (46.7%) in the neonatal period. Antepartum deaths were due to unspecified causes (59%), chromosomal abnormalities (21%) or problems related to fetal growth (14%). Intrapartum deaths followed acute intrapartum events (69%); neonatal deaths followed consequences of low birthweight/ prematurity (31%), chromosomal abnormalities (26%), or unspecified causes in healthy mothers (25%). Mothers were often healthy; 53%, 38% and 45% in the antepartum, intrapartum and neonatal death groups, respectively. Where there was a maternal condition, it was most often maternal medical conditions, and complications of placenta, cord and membranes., Conclusions: The ICD-PM can be a globally applicable perinatal death classification system that emphasises the need for a focus on the mother-baby dyad as we move beyond 2015., Tweetable Abstract: ICD-PM is a global system that classifies perinatal deaths and links them to maternal conditions., (© 2016 Royal College of Obstetricians and Gynaecologists The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.)

Background: Each year, about 5.3 million babies die in the perinatal period. Understanding of causes of death is critical for prevention, yet there is no globally acceptable classification system. Instead, many disparate systems have been developed and used. We aimed to identify all systems used or created between 2009 and 2014, with their key features, including extent of alignment with the International Classification of Diseases (ICD) and variation in features by region, to inform the World Health Organization's development of a new global approach to classifying perinatal deaths., Methods: A systematic literature review (CINAHL, EMBASE, Medline, Global Health, and PubMed) identified published and unpublished studies and national reports describing new classification systems or modifications of existing systems for causes of perinatal death, or that used or tested such systems, between 2009 and 2014. Studies reporting ICD use only were excluded. Data were independently double-extracted (except from non-English publications). Subgroup analyses explored variation by extent and region., Results: Eighty-one systems were identified as new, modifications of existing systems, or having been used between 2009 and 2014, with an average of ten systems created/modified each year. Systems had widely varying characteristics: (i) comprehensiveness (40 systems classified both stillbirths and neonatal deaths); (ii) extent of use (systems were created in 28 countries and used in 40; 17 were created for national use; 27 were widely used); (iii) accessibility (three systems available in e-format); (iv) underlying cause of death (64 systems required a single cause of death); (v) reliability (10 systems tested for reliability, with overall Kappa scores ranging from .35-.93); and (vi) ICD alignment (17 systems used ICD codes). Regional databases were not searched, so system numbers may be underestimated. Some non-differential misclassification of systems was possible., Conclusions: The plethora of systems in use, and continuing system development, hamper international efforts to improve understanding of causes of death. Recognition of the features of currently used systems, combined with a better understanding of the drivers of continued system creation, may help the development of a truly effective global system.

Background: To reduce the burden of 5.3 million stillbirths and neonatal deaths annually, an understanding of causes of deaths is critical. A systematic review identified 81 systems for classification of causes of stillbirth (SB) and neonatal death (NND) between 2009 and 2014. The large number of systems hampers efforts to understand and prevent these deaths. This study aimed to assess the alignment of current classification systems with expert-identified characteristics for a globally effective classification system., Methods: Eighty-one classification systems were assessed for alignment with 17 characteristics previously identified through expert consensus as necessary for an effective global system. Data were extracted independently by two authors. Systems were assessed against each characteristic and weighted and unweighted scores assigned to each. Subgroup analyses were undertaken by system use, setting, type of death included and type of characteristic., Results: None of the 81 systems were aligned with more than 9 of the 17 characteristics; most (82 %) were aligned with four or fewer. On average, systems were aligned with 19 % of characteristics. The most aligned system (Frøen 2009-Codac) still had an unweighted score of only 9/17. Alignment with individual characteristics ranged from 0 to 49 %. Alignment was somewhat higher for widely used as compared to less used systems (22 % v 17 %), systems used only in high income countries as compared to only in low and middle income countries (20 % vs 16 %), and systems including both SB and NND (23 %) as compared to NND-only (15 %) and SB-only systems (13 %). Alignment was higher with characteristics assessing structure (23 %) than function (15 %)., Conclusions: There is an unmet need for a system exhibiting all the characteristics of a globally effective system as defined by experts in the use of systems, as none of the 81 contemporary classification systems assessed was highly aligned with these characteristics. A particular concern in terms of global effectiveness is the lack of alignment with "ease of use" among all systems, including even the most-aligned. A system which meets the needs of users would have the potential to become the first truly globally effective classification system.

Background: Despite the global burden of perinatal deaths, there is currently no single, globally-acceptable classification system for perinatal deaths. Instead, multiple, disparate systems are in use world-wide. This inconsistency hinders accurate estimates of causes of death and impedes effective prevention strategies. The World Health Organisation (WHO) is developing a globally-acceptable classification approach for perinatal deaths. To inform this work, we sought to establish a consensus on the important characteristics of such a system., Methods: A group of international experts in the classification of perinatal deaths were identified and invited to join an expert panel to develop a list of important characteristics of a quality global classification system for perinatal death. A Delphi consensus methodology was used to reach agreement. Three rounds of consultation were undertaken using a purpose built on-line survey. Round one sought suggested characteristics for subsequent scoring and selection in rounds two and three., Results: The panel of experts agreed on a total of 17 important characteristics for a globally-acceptable perinatal death classification system. Of these, 10 relate to the structural design of the system and 7 relate to the functional aspects and use of the system., Conclusion: This study serves as formative work towards the development of a globally-acceptable approach for the classification of the causes of perinatal deaths. The list of functional and structural characteristics identified should be taken into consideration when designing and developing such a system.

Background: The official WHO estimates of preterm birth are an essential global resource for assessing the burden of preterm birth and developing public health programmes and policies. This protocol describes the methods that will be used to identify, critically appraise and analyse all eligible preterm birth data, in order to develop global, regional and national level estimates of levels and trends in preterm birth rates for the period 1990 - 2014., Methods: We will conduct a systematic review of civil registration and vital statistics (CRVS) data on preterm birth for all WHO Member States, via national Ministries of Health and Statistics Offices. For Member States with absent, limited or lower-quality CRVS data, a systematic review of surveys and/or research studies will be conducted. Modelling will be used to develop country, regional and global rates for 2014, with time trends for Member States where sufficient data are available. Member States will be invited to review the methodology and provide additional eligible data via a country consultation before final estimates are developed and disseminated., Discussion: This research will be used to generate estimates on the burden of preterm birth globally for 1990 to 2014. We invite feedback on the methodology described, and call on the public health community to submit pertinent data for consideration., Trial Registration: Registered at PROSPERO CRD42015027439 CONTACT: pretermbirth@who.int.

Scaling up an emergency obstetric and neonatal care (EmONC) programme entails reaching a larger number of people in a potentially broader geographical area. Multiple strategies requiring simultaneous attention should be deployed. This paper provides a framework for understanding the implementation, scale-up and sustainability of such programmes. We reviewed the existing literature and drew on our experience in scaling up the Essential Steps in the Management of Obstetric Emergencies (ESMOE) programme in South Africa. We explore the non-linear change process and conditions to be met for taking an existing EmONC programme to scale. Important concepts cutting across all components of a programme are equity, quality and leadership. Conditions to be met include appropriate awareness across the board and a policy environment that leads to the following: commitment, health systems-strengthening actions, allocation of resources (human, financial and capital/material), dissemination and training, supportive supervision and monitoring and evaluation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: While there is widespread acknowledgment of the need for improved quality and quantity of information on births and deaths, there has been less movement towards systematically capturing and reviewing the causes and avoidable factors linked to deaths, in order to affect change. This is particularly true for stillbirths and neonatal deaths which can fall between different health care providers and departments. Maternal and perinatal mortality audit applies to two of the five objectives in the Every Newborn Action Plan but data on successful approaches to overcome bottlenecks to scaling up audit are lacking., Methods: We reviewed the current evidence for facility-based perinatal mortality audit with a focus on low- and middle-income countries and assessed the status of mortality audit policy and implementation. Based on challenges identified in the literature, key challenges to completing the audit cycle and affecting change were identified across the WHO health system building blocks, along with solutions, in order to inform the process of scaling up this strategy with attention to quality., Results: Maternal death surveillance and review is moving rapidly with many countries enacting and implementing policies and with accountability beyond the single facility conducting the audits. While 51 priority countries report having a policy on maternal death notification in 2014, only 17 countries have a policy for reporting and reviewing stillbirths and neonatal deaths. The existing evidence demonstrates the potential for audit to improve birth outcomes, only if the audit cycle is completed. The primary challenges within the health system building blocks are in the area of leadership and health information. Examples of successful implementation exist from high income countries and select low- and middle-income countries provide valuable learning, especially on the need for leadership for effective audit systems and on the development and the use of clear guidelines and protocols in order to ensure that the audit cycle is completed., Conclusions: Health workers have the power to change health care routines in daily practice, but this must be accompanied by concrete inputs at every level of the health system. The system requires data systems including consistent cause of death classification and use of best practice guidelines to monitor performance, as well as leaders to champion the process, especially to ensure a no-blame environment, and to access change agents at other levels to address larger, systemic challenges.