Predictors of Phthalate Metabolites Exposure among Healthy Pregnant Women in the United States, 2010-2015.

Phthalate use and the concentrations of their metabolites in humans vary by geographic region, race, ethnicity, sex, product use and other factors. Exposure during pregnancy may be associated with detrimental reproductive and developmental outcomes. No studies have evaluated the predictors of exposure to a wide range of phthalate metabolites in a large, diverse population. We examined the determinants of phthalate metabolites in a cohort of racially/ethnically diverse nulliparous pregnant women. We report on urinary metabolites of nine parent phthalates or replacement compounds-Butyl benzyl phthalate (BBzP), Diisobutyl phthalate (DiBP), Diethyl phthalate (DEP), Diisononyl phthalate (DiNP), D-n-octyl phthalate (DnOP), Di-2-ethylhexyl terephthalate (DEHTP), Di-n/i-butyl phthalate (DnBP), Di-isononyl phthalate (DiNP) and Di-(2-ethylhexyl) phthalate (DEHP) from urine collected up to three times from 953 women enrolled in the Nulliparous Mothers To Be Study. Phthalate metabolites were adjusted for specific gravity. Generalized estimating equations (GEEs) were used to identify the predictors of each metabolite. Overall predictors include age, race and ethnicity, education, BMI and clinical site of care. Women who were Non-Hispanic Black, Hispanic or Asian, obese or had lower levels of education had higher concentrations of selected metabolites. These findings indicate exposure patterns that require policies to reduce exposure in specific subgroups.

Ending preventable stillbirths and improving bereavement care: a scorecard for high- and upper-middle income countries.

BACKGROUND: Despite progress, stillbirth rates in many high- and upper-middle income countries remain high, and the majority of these deaths are preventable. We introduce the Ending Preventable Stillbirths (EPS) Scorecard for High- and Upper Middle-Income Countries, a tool to track progress against the Lancet's 2016 EPS Series Call to Action, fostering transparency, consistency and accountability. METHODS: The Scorecard for EPS in High- and Upper-Middle Income Countries was adapted from the Scorecard for EPS in Low-Income Countries, which includes 20 indicators to track progress against the eight Call to Action targets. The Scorecard for High- and Upper-Middle Income Countries includes 23 indicators tracking progress against these same Call to Action targets. For this inaugural version of the Scorecard, 13 high- and upper-middle income countries supplied data. Data were collated and compared between and within countries. RESULTS: Data were complete for 15 of 23 indicators (65%). Five key issues were identified: (1) there is wide variation in stillbirth rates and related perinatal outcomes, (2) definitions of stillbirth and related perinatal outcomes vary widely across countries, (3) data on key risk factors for stillbirth are often missing and equity is not consistently tracked, (4) most countries lack guidelines and targets for critical areas for stillbirth prevention and care after stillbirth and have not set a national stillbirth rate target, and (5) most countries do not have mechanisms in place for reduction of stigma or guidelines around bereavement care. CONCLUSIONS: This inaugural version of the Scorecard for High- and Upper-Middle Income Countries highlights important gaps in performance indicators for stillbirth both between and within countries. The Scorecard provides a basis for future assessment of progress and can be used to help hold individual countries accountable, especially for reducing stillbirth inequities in disadvantaged groups.

Improving maternal and newborn health and reducing stillbirths in the Western Pacific Region - current situation and the way forward.

Despite positive trends in many indicators, there remains an unacceptable burden of preventable maternal, newborn deaths and stillbirths every year. This paper provides an overview of the maternal and perinatal outcomes across 22 Pacific Island Countries and Territories, including Papua New Guinea. We highlight some unique challenges and provide examples of initiatives in three of the larger countries to contribute to safer childbirth. There are high maternal and perinatal morbidity and mortality rates in many of the countries, although reliable data are limited. There are currently no data relating to the burden of intrapartum-related maternal and perinatal morbidity or stillbirth or the quality of intrapartum care. Varying definitions across countries for perinatal indicators mean that meaningful comparisons are difficult and unreliable. There is need for midwives and other maternal and newborn health providers to improve maternal and newborn indicators as countries advance towards the 2030 Sustainable Development Goals.

Current approach and attitudes toward neonatal near-miss and perinatal audits: An exploratory international survey.

BACKGROUND: Combined with perinatal mortality review, neonatal near-miss (NNM) audit has the potential to inform strategies to better prevent adverse perinatal outcomes. Nonetheless, there is lack of standardised definitions of NNM and limited evidence of implementation of NNM audits. AIM: To describe definitions of NNM and assess current approaches and attitudes toward perinatal mortality and morbidity audit. MATERIALS AND METHODS: Online survey from December 2021 to February 2022, with a mix of Likert scales, polar, pool, multi-choice, and open-ended questions, disseminated through national and international organisations to perinatal healthcare workers from high-income countries. RESULTS: One hundred and twenty participants came from Australia (n = 86), New Zealand (n = 18), Canada (n = 7), USA (n = 4), Netherlands (n = 2), other countries (n = 3). Neonatologists (35%), midwives (21.7%), obstetricians (12.5%), neonatal nurse practitioners (11.7%) and others (23.3%) responded. Most respondents thought the main characteristics to define NNM were birth asphyxia needing therapeutic hypothermia (68.3%), unexpected resuscitation at birth (67.5%), need for intubation/chest compression/adrenaline (65.0%) and metabolic acidosis at birth (60.0%). There were 97.5% of participants who considered NNM important for identifying cases for perinatal morbidity audits. However, only 10.0% of their institutions used a NNM definition. Overall, 98.4% of participants considered perinatal mortality and morbidity audits important to prevent adverse outcomes. CONCLUSION: Neonatal near-miss audit is viewed as a valuable tool to reduce adverse neonatal outcomes. There was reasonable consensus that NNM encompassed evidence of birth asphyxia and/or advanced neonatal resuscitation. Data from this international survey identifies a starting point for a consensus definition of NNM, which can be used for perinatal audits to identify opportunities for improvement.

Protocol for the development of a core outcome set for stillbirth care research (iCHOOSE Study).

INTRODUCTION: Stillbirth is associated with significant physical, psychosocial and economic consequences for parents, families, wider society and the healthcare system. There is emerging momentum to design and evaluate interventions for care after stillbirth and in subsequent pregnancies. However, there is insufficient evidence to inform clinical practice compounded by inconsistent outcome reporting in research studies. To address this paucity of evidence, we plan to develop a core outcome set for stillbirth care research, through an international consensus process with key stakeholders including parents, healthcare professionals and researchers. METHODS AND ANALYSIS: The development of this core outcome set will be divided into five distinct phases: (1) Identifying potential outcomes from a mixed-methods systematic review and analysis of interviews with parents who have experienced stillbirth; (2) Creating a comprehensive outcome long-list and piloting of a Delphi questionnaire using think-aloud interviews; (3) Choosing the most important outcomes by conducting an international two-round Delphi survey including high-income, middle-income and low-income countries; (4) Deciding the core outcome set by consensus meetings with key stakeholders and (5) Dissemination and promotion of the core outcome set. A parent and public involvement panel and international steering committee has been convened to coproduce every stage of the development of this core outcome set. ETHICS AND DISSEMINATION: Ethical approval for the qualitative interviews has been approved by Berkshire Ethics Committee REC Reference 12/SC/0495. Ethical approval for the think-aloud interviews, Delphi survey and consensus meetings has been awarded from the University of Bristol Faculty of Health Sciences Research Ethics Committee (Reference number: 116535). The dissemination strategy is being developed with the parent and public involvement panel and steering committee. Results will be published in peer-reviewed specialty journals, shared at national and international conferences and promoted through parent organisations and charities. PROSPERO REGISTRATION NUMBER: CRD42018087748.

Multicountry study protocol of COCOON: COntinuing Care in COVID-19 Outbreak global survey of New, expectant, and bereaved parent experiences.

INTRODUCTION: Globally, the COVID-19 pandemic has significantly disrupted the provision of healthcare and efficiency of healthcare systems and is likely to have profound implications for pregnant and postpartum women and their families including those who experience the tragedy of stillbirth or neonatal death. This study aims to understand the psychosocial impact of COVID-19 and the experiences of parents who have accessed maternity, neonatal and bereavement care services during this time. METHODS AND ANALYSIS: An international, cross-sectional, online and/or telephone-based/face-to-face survey is being administered across 15 countries and available in 11 languages. New, expectant and bereaved parents during the COVID-19 pandemic will be recruited. Validated psychometric scales will be used to measure psychosocial well-being. Data will be analysed descriptively and by assessing multivariable associations of the outcomes with explanatory factors. In seven of these countries, bereaved parents will be recruited to a nested, qualitative interview study. The data will be analysed using a grounded theory analysis (for each country) and thematic framework analysis (for intercountry comparison) to gain further insights into their experiences. ETHICS AND DISSEMINATION: Ethics approval for the multicountry online survey, COCOON, has been granted by the Mater Misericordiae Human Research Ethics Committee in Australia (reference number: AM/MML/63526). Ethics approval for the nested qualitative interview study, PUDDLES, has been granted by the King's College London Biomedical & Health Sciences, Dentistry, Medicine and Natural & Mathematical Sciences Research Ethics Subcommittee (reference number: HR-19/20-19455) in the UK. Local ethics committee approvals were granted in participating countries where required. Results of the study will be published in international peer-reviewed journals and through parent support organisations. Findings will contribute to our understanding of delivering maternity care services, particularly bereavement care, in high-income, lower middle-income and low-income countries during this or future health crises.

Parents' experiences of care offered after stillbirth: An international online survey of high and middle-income countries.

BACKGROUND: Stillbirth, the death of a baby before birth, is associated with significant psychological and social consequences that can be mitigated by respectful and supportive bereavement care. The absence of high-level evidence to support the broad scope of perinatal bereavement practices means that offering a range of options identified as valued by parents has become an important indicator of care quality. This study aimed to describe bereavement care practices offered to parents across different high-income and middle-income countries. METHODS: An online survey of parents of stillborn babies was conducted between December 2014 and February 2015. Frequencies of nine practices were compared between high-income and middle-income countries. Differences in proportions of reported practices and their associated odds ratios were calculated to compare high-income and middle-income countries. RESULTS: Over three thousand parents (3041) with a self-reported stillbirth in the preceding five years from 40 countries responded. Fifteen countries had atleast 40 responses. Significant differences in the prevalence of offering nine bereavement care practices were reported by women in high-income countries (HICs) compared with women in middle-income countries (MICs). All nine practices were reported to occur significantly more frequently by women in HICs, including opportunity to see and hold their baby (OR = 4.8, 95% CI 4.0-5.9). The widespread occurrence of all nine practices was reported only for The Netherlands. CONCLUSIONS: Bereavement care after stillbirth varies between countries. Future research should look at why these differences occur, their impact on parents, and whether differences should be addressed, particularly how to support effective communication, decision-making, and follow-up care.

Systematic review: fetal death reporting and risk in Zika-affected pregnancies.

OBJECTIVES: Zika virus is linked to several adverse pregnancy outcomes. We assessed whether Zika infection during pregnancy is associated with increased risk of foetal death (miscarriage, stillbirth, abortion) and whether there is incomplete reporting of such deaths. METHODS: We searched PubMed, Embase, CINAHL, Web of Science and LILACS for studies reporting Zika-affected completed pregnancies (ending in foetal death or live birth), excluding studies whose aim required live birth. Studies 'allowed' foetal death if their populations were defined to encompass both live births and foetal deaths, regardless of whether deaths were actually found. Two authors independently extracted data and assessed study quality. Foetal death absolute and relative risks in Zika-affected vs. unaffected pregnancies were calculated. RESULTS: We found 108 reports including 24 699 completed, Zika-affected pregnancies. The median absolute risk in 37 studies of completed, Zika-affected pregnancies was 6.3% (IQR 3.2%, 10.6%) for foetal death and 5.9% (IQR 0%, 29.1%) for non-fatal adverse outcomes (e.g. microcephaly). More studies allowed non-fatal adverse outcomes (95%) than foetal death (58%). Of studies which allowed them, 94% found at least one foetal death. In 37% of reports, it was unknown whether foetal deaths were allowed. Only one study had sufficient data to estimate a foetal death relative risk (11.05, 95% CI 3.43, 35.55). CONCLUSIONS: Evidence was insufficient to determine whether foetal death risk is higher in Zika-affected pregnancies, but suggests quality of foetal death reporting should be improved, including stating whether foetal deaths were found, how many, and at what gestational ages, or justifying their exclusion.

OBJECTIFS: Le virus Zika est lié à plusieurs issues défavorables de la grossesse. Nous avons évalué si l'infection à Zika pendant la grossesse était associée à un risque accru de mort fœtale (fausse couche, mortinaissance, avortement) et s'il y avait une déclaration incomplète de ces décès. MÉTHODES: Nous avons recherché dans PubMed, EMBASE, Cinahl, Web of Science et LILACS des études rapportant des grossesses terminées touchées par le virus Zika (se terminant par une mort fœtale ou une naissance vivante), à l'exclusion des études dont l'objectif nécessitait une naissance vivante. Les études «autorisaient¼ la mort fœtale si leur population était définie comme englobant à la fois les naissances vivantes et les décès fœtaux, indépendamment du fait que des décès aient été effectivement constatés. Deux auteurs ont indépendamment extrait les données et évalué la qualité des études. Les risques absolus et relatifs de mortalité fœtale dans les grossesses affectées par Zika par rapport aux grossesses non affectées ont été calculés. RÉSULTATS: Nous avons trouvé 108 reports dont 24.699 grossesses terminées et affectées par le virus Zika. Le risque médian absolu dans 37 études portant sur des grossesses terminées affectées par Zika était de 6,3% (IQR 3,2%, 10,6%) pour la mort fœtale et de 5,9% (IQR 0%, 29,1%) pour les issues indésirables non mortelles (par exemple microcéphalie). Plus d'études ont «autorisé¼ des résultats indésirables non mortels (95%) que la mort fœtale (58%). Parmi les études qui les ont «autorisé¼, 94% ont trouvé au moins un décès fœtal. Dans 37% des rapports, il n'est pas indiqué si la mort fœtale avait été «autorisée¼. Une seule étude contenait des données suffisantes pour estimer un risque relatif de mort fœtale (11,05 ; IC95%: 3,43, 35,55). CONCLUSIONS: Les données étaient insuffisantes pour déterminer si le risque de mort fœtale est plus élevé dans les grossesses touchées par le virus Zika, mais suggèrent que la qualité des reports sur les décès fœtaux devrait être améliorée, notamment en indiquant si des décès fœtaux ont été constatés, combien et à quel âge gestationnel, ou justifiant leur exclusion.

Stillbirth in Australia 1: The road to now: Two decades of stillbirth research and advocacy in Australia.

Stillbirth is a major public health problem with an enormous mortality burden and psychosocial impact on parents, families and the wider community both globally and in Australia. In 2015, Australia's late gestation stillbirth rate was over 30% higher than that of the best-performing countries globally, highlighting the urgent need for action. We present an overview of the foundations which led to the establishment of Australia's NHMRC Centre of Research Excellence in Stillbirth (Stillbirth CRE) in 2017 and highlight key activities in the following areas: Opportunities to expand and improve collaborations between research teams; Supporting the conduct and development of innovative, high quality, collaborative research that incorporates a strong parent voice; Promoting effective translation of research into health policy and/or practice; and the Regional and global work of the Stillbirth CRE. We highlight the first-ever Senate Inquiry into Stillbirth in Australia in 2018. These events ultimately led to the development of a National Stillbirth Action and Implementation Plan for Australia with the aims of reducing stillbirth rates by 20% over the next five years, reducing the disparity in stillbirth rates between advantaged and disadvantaged communities, and improving care for all families who experience this loss.

Classification of causes and associated conditions for stillbirths and neonatal deaths.

Accurate and consistent classification of causes and associated conditions for perinatal deaths is essential to inform strategies to reduce the five million which occur globally each year. With the majority of deaths occurring in low- and middle-income countries (LMICs), their needs must be prioritised. The aim of this paper is to review the classification of perinatal death, the contemporary classification systems including the World Health Organization's International Classification of Diseases - Perinatal Mortality (ICD-PM), and next steps. During the period from 2009 to 2014, a total of 81 new or modified classification systems were identified with the majority developed in high-income countries (HICs). Structure, definitions and rules and therefore data on causes vary widely and implementation is suboptimal. Whereas system testing is limited, none appears ideal. Several systems result in a high proportion of unexplained stillbirths, prompting HICs to use more detailed systems that require data unavailable in low-income countries. Some systems appear to perform well across these different settings. ICD-PM addresses some shortcomings of ICD-10 for perinatal deaths, but important limitations remain, especially for stillbirths. A global approach to classification is needed and seems feasible. The new ICD-PM system is an important step forward and improvements will be enhanced by wide-scale use and evaluation. Implementation requires national-level support and dedicated resources. Future research should focus on implementation strategies and evaluation methods, defining placental pathologies, and ways to engage parents in the process.

Evaluation of an international educational programme for health care professionals on best practice in the management of a perinatal death: IMproving Perinatal mortality Review and Outcomes Via Education (IMPROVE).

BACKGROUND: Stillbirths and neonatal deaths are devastating events for both parents and clinicians and are global public health concerns. Careful clinical management after these deaths is required, including appropriate investigation and assessment to determine cause (s) to prevent future losses, and to improve bereavement care for families. An educational programme for health care professionals working in maternal and child health has been designed to address these needs according to the Perinatal Society of Australia and New Zealand Guideline for Perinatal Mortality: IMproving Perinatal mortality Review and Outcomes Via Education (IMPROVE). The programme has a major focus on stillbirth and is delivered as six interactive skills-based stations. We aimed to determine participants' pre- and post-programme knowledge of and confidence in the management of perinatal deaths, along with satisfaction with the programme. We also aimed to determine suitability for international use. METHODS: The IMPROVE programme was delivered to health professionals in maternity hospitals in all seven Australian states and territories and modified for use internationally with piloting in Vietnam, Fiji, and the Netherlands (with the assistance of the International Stillbirth Alliance, ISA). Modifications were made to programme materials in consultation with local teams and included translation for the Vietnam programme. Participants completed pre- and post-programme evaluation questionnaires on knowledge and confidence on six key components of perinatal death management as well as a satisfaction questionnaire. RESULTS: Over the period May 2012 to May 2015, 30 IMPROVE workshops were conducted, including 26 with 758 participants in Australia and four with 136 participants internationally. Evaluations showed a significant improvement between pre- and post-programme knowledge and confidence in all six stations and overall, and a high degree of satisfaction in all settings. CONCLUSIONS: The IMPROVE programme has been well received in Australia and in three different international settings and is now being made available through ISA. Future research is required to determine whether the immediate improvements in knowledge are sustained with less causes of death being classified as unknown, changes in clinical practice and improvement in parents' experiences with care. The suitability for this programme in low-income countries also needs to be established.

Seeking order amidst chaos: a systematic review of classification systems for causes of stillbirth and neonatal death, 2009-2014.

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.

Classification systems for causes of stillbirth and neonatal death, 2009-2014: an assessment of alignment with characteristics for an 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.

Characteristics of a global classification system for perinatal deaths: a Delphi consensus study.

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.

Stillbirths: recall to action in high-income countries.

Variation in stillbirth rates across high-income countries and large equity gaps within high-income countries persist. If all high-income countries achieved stillbirth rates equal to the best performing countries, 19,439 late gestation (28 weeks or more) stillbirths could have been avoided in 2015. The proportion of unexplained stillbirths is high and can be addressed through improvements in data collection, investigation, and classification, and with a better understanding of causal pathways. Substandard care contributes to 20-30% of all stillbirths and the contribution is even higher for late gestation intrapartum stillbirths. National perinatal mortality audit programmes need to be implemented in all high-income countries. The need to reduce stigma and fatalism related to stillbirth and to improve bereavement care are also clear, persisting priorities for action. In high-income countries, a woman living under adverse socioeconomic circumstances has twice the risk of having a stillborn child when compared to her more advantaged counterparts. Programmes at community and country level need to improve health in disadvantaged families to address these inequities.