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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.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.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).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.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 «autorisaient» 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 «autorisé» des résultats indésirables non mortels (95%) que la mort fœtale (58%). Parmi les études qui les ont «autorisé», 94% ont trouvé au moins un décès fœtal. Dans 37% des rapports, il n’est pas indiqué si la mort fœtale avait été «autorisée». Une seule étude contenait des données suffisantes pour estimer un risque relatif de mort fœtale (11,05 ; IC95%: 3,43, 35,55).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.

It has become increasingly evident the serotonergic (5-hydroxytryptamine, 5-HT) system is an important central neuronal network disrupted following neonatal hypoxic-ischemic (HI) insults. Serotonin acts via a variety of receptor subtypes that are differentially associated with behavioural and cognitive mechanisms. The 5-HT7 receptor is purported to play a key role in epilepsy, anxiety, learning and memory and neuropsychiatric disorders. Furthermore, the 5-HT7 receptor is highly localized in brain regions damaged following neonatal HI insults. Utilising our well-established neonatal HI model in the postnatal day 3 (P3) rat pup we demonstrated a significant decrease in levels of the 5-HT7 protein in the frontal cortex, thalamus and brainstem one week after insult. We also observed a relative decrease in both the cytosolic and membrane fractions of 5-HT7. The 5-HT7 receptor was detected on neurons throughout the cortex and thalamus, and 5-HT cell bodies in the brainstem. However we found no evidence of 5-HT7 co-localisation on microglia or astrocytes. Moreover, minocycline treatment did not significantly prevent the HI-induced reductions in 5-HT7. In conclusion, neonatal HI injury caused significant disruption to 5-HT7 receptors in the forebrain and brainstem. Yet the use of minocycline to inhibit activated microglia, did not prevent the HI-induced changes in 5-HT7 expression.

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. (C) 2017 Elsevier Ltd. All rights reserved.

© 2019 Australian College of Midwives Background: ‘Bundles of care’ are being implemented to improve key practice gaps in perinatal care. As part of our development of a stillbirth prevention bundle, we consulted with Australian maternity care providers. Objective: To gain the insights of Australian maternity care providers to inform the development and implementation of a bundle of care for stillbirth prevention. Methods: A 2018 on-line survey of hospitals providing maternity services included 55 questions incorporating multiple choice, Likert items and open text. A senior clinician at each site completed the survey. The survey asked questions about practices related to fetal growth restriction, decreased fetal movements, smoking cessation, intrapartum fetal monitoring, maternal sleep position and perinatal mortality audit. The objectives were to assess which elements of care were most valued; best practice frequency; and, barriers and enablers to implementation. Results: 227 hospitals were invited with 83 (37%) responding. All proposed elements were perceived as important. Hospitals were least likely to follow best practice recommendations “all the time” for smoking cessation support (

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.

It has become increasingly evident the serotonergic (5-hydroxytryptamine, 5-HT) system is an important central neuronal network disrupted following neonatal hypoxic-ischemic (HI) insults. Serotonin acts via a variety of receptor subtypes that are differentially associated with behavioural and cognitive mechanisms. The 5-HT

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. Electronic supplementary material The online version of this article (doi:10.1186/s12884-016-1071-0) contains supplementary material, which is available to authorized users.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12884-016-1040-7) contains supplementary material, which is available to authorized users.

${\bf Background}$ 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. ${\bf Methods}$ 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. ${\bf Results}$ 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. ${\bf Conclusion}$ 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., This project was initially undertaken as part of the Harmonized Reproductive Health Registries project through the Norwegian Institute of Public Health in Partnership with the Mater Medical Research Institute, Brisbane, Australia, and in collaboration with the Department of Reproductive Health and Research, WHO., This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by BioMed Central.

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.

Background Preterm birth is a major cause of perinatal mortality and morbidity. Cyclo-oxygenase (COX) inhibitors inhibit uterine contractions, are easily administered and appear to have few maternal side effects. However, adverse effects have been reported in the fetus and newborn as a result of exposure to COX inhibitors. Objectives To assess the effects on maternal and neonatal outcomes of COX inhibitors administered as a tocolytic agent to women in preterm labour when compared with (i) placebo or no intervention and (ii) other tocolytics. In addition, to compare the effects of non-selective COX inhibitors with COX-2 selective inhibitors. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (24 August 2014). We also contacted recognised experts and searched reference lists of retrieved studies. Selection criteria All published and unpublished randomised trials in which COX inhibitors were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation. Data collection and analysis Two review authors independently evaluated methodological quality and extracted data. We sought additional information from study authors. Results are presented using risk ratio (RR; dichotomous data) and mean difference (MD; continuous data) with 95% confidence interval (CI). The number needed to treat for benefit (NNTB) and the number needed to treat for harm (NNTH) were calculated for statistically different categorical outcomes. Main results With the addition of seven studies with a total of 684 women, this review now includes outcome data from 20 studies including 1509 women. The non-selective COX inhibitor indomethacin was used in 15 studies. The overall quality of the included studies was considered moderate to low. Three small studies (102 women), two of which were conducted in the 1980's, compared COX inhibition (indomethacin only) with placebo. No difference was shown in birth less than 48 hours after trial entry (average RR 0.20, 95% CI 0.03 to 1.28; two studies with 70 women). Indomethacin resulted in a reduction in preterm birth (before completion of 37 weeks of gestation) in one small study (36 women) (RR 0.21, 95% CI 0.07 to 0.62; NNTB 2, 95% CI 2 to 4); and an increase in gestational age at birth (average MD 3.59 weeks, 95% CI 0.65 to 6.52; two studies with 66 women) and birthweight (MD 716.34 g, 95% CI 425.52 to 1007.16; two studies with 67 infants). No difference was shown in measures of neonatal morbidity or neonatal mortality. Compared with betamimetics, COX inhibitors resulted in a reduction in birth less than 48 hours after trial entry (RR 0.27, 95% CI 0.08 to 0.96; NNTB 7, 95% CI 6 to 120; two studies with 100 women) and preterm birth (before completion of 37 weeks of gestation) (RR 0.53, 95% CI 0.28 to 0.99; NNTB 6, 95% CI 4 to 236; two studies with 80 women) although no benefit was shown in terms of neonatal morbidity or mortality. COX inhibition was also associated with fewer maternal adverse affects compared with betamimetics (RR 0.19, 95% CI 0.11 to 0.31; NNTB 3, 95% CI 2 to 3; five studies with 248 women) and maternal adverse effects requiring cessation of treatment (average RR 0.09, 95% CI 0.02 to 0.49; NNTB 5, CI 95% 5 to 9; three studies with 166 women). No differences were shown when comparing COX inhibitors with magnesium sulphate (MgSO4) (seven studies with 792 women) or calcium channel blockers (CCBs) (two studies with 230 women) in terms of prolonging pregnancy or for any fetal/neonatal outcomes. There were also no differences in very preterm birth (before completion of 34 weeks of gestation) and no maternal deaths occurred in the one study that reported on this outcome. However COX inhibitors resulted in fewer maternal adverse affects when compared with MgSO4 (RR 0.39, 95% CI 0.25 to 0.62; NNTB 11, 95% CI 9 to 17; five studies with 635 women). A comparison of non-selective COX inhibitors versus any COX-2 inhibitor (two studies with 54 women) did not demonstrate any differences in maternal, fetal or neonatal outcomes. No data were available to assess COX inhibitors compared with oxytocin receptor antagonists (ORAs). Further, no data were available on extremely preterm birth (before 28 weeks of gestation), longer-term infant outcomes or costs. Authors' conclusions In this review, no clear benefit for COX inhibitors was shown over placebo or any other tocolytic agents. While some benefit was demonstrated in terms of postponement of birth for COX inhibitors over placebo and betamimetics and also maternal adverse effects over betamimetics and MgSO4, due to the limitations of small numbers, minimal data on safety, lack of longer-term outcomes and generally low quality of the studies included in this review, we conclude that there is insufficient evidence on which to base decisions about the role of COX inhibition for women in preterm labour. Further well-designed tocolytic studies are required to determine short- and longer-term infant benefit of COX inhibitors over placebo and other tocolytics, particularly CCBs and ORAs. Another important focus for future studies is identifying whether COX-2 inhibitors are superior to non-selective COX inhibitors. All future studies on tocolytics for women in preterm labour should assess longer-term effects into early childhood and also costs.