Survey of Australian maternity hospitals to inform development and implementation of a stillbirth prevention 'bundle of care'.

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 (<50%), risk assessment for fetal growth restriction (<40%) and advice on sleep position (<20%). Time constraints, absence of clear guidelines and lack of continuity of carer were recognised as barriers to implementation across care practices. CONCLUSIONS: Areas for practice improvement were evident. All elements of care were valued, with increasing awareness of safe sleeping position perceived as less important. There is strong support from maternity care providers across Australia for a bundle of care to reduce stillbirth.

Making stillbirths visible: a systematic review of globally reported causes of stillbirth.

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.

Neonatal hypoxia-ischaemia disrupts descending neural inputs to dorsal raphé nuclei.

Neuronal losses have been shown to occur in the brainstem following a neonatal hypoxic-ischaemic (HI) insult. In particular serotonergic neurons, situated in the dorsal raphé nuclei, appear to be vulnerable to HI injury. Nonetheless the mechanisms contributing to losses of serotonergic neurons in the brainstem remain to be elucidated. One possible mechanism is that disruption of neural projections from damaged forebrain areas to dorsal raphé nuclei may play a role in the demise of serotonergic neurons. To test this, postnatal day 3 (P3) rat pups underwent unilateral common carotid artery ligation followed by hypoxia (6% O2 for 30 min). On P38 a retrograde tracer, fluorescent-coupled choleratoxin b, was deposited in the dorsal raphé dorsal (DR dorsal) nucleus or the dorsal raphé ventral (DR ventral) nucleus. Compared to control animals, P3 HI animals had significant losses of retrogradely labelled neurons in the medial prefrontal cortex, preoptic area and lateral habenula after tracer deposit in the DR dorsal nucleus. On the other hand, after tracer deposit in the DR ventral nucleus, we found significant reductions in numbers of retrogradely labelled neurons in the hypothalamus, preoptic area and medial amygdala in P3 HI animals compared to controls. Since losses of descending inputs are associated with decreases in serotonergic neurons in the brainstem raphé nuclei, we propose that disruption of certain descending neural inputs from the forebrain to the DR dorsal and the DR ventral nuclei may contribute to losses of serotonergic neurons after P3 HI. It is important to delineate the phenotypes of different neuronal networks affected by neonatal HI, and the mechanisms underpinning this damage, so that interventions can be devised to target and protect axons from the harmful effects of neonatal HI.

Ibuprofen inhibits neuroinflammation and attenuates white matter damage following hypoxia-ischemia in the immature rodent brain.

Damage to major white matter tracts is a hallmark mark feature of hypoxic-ischemic (HI) brain injury in the preterm neonate. There is, however, no therapeutic intervention to treat this injury. Neuroinflammation is thought to play a prominent role in the pathogenesis of the HI-induced white matter damage but identification of the key mediators that constitute the inflammatory response remain to be fully elucidated. Cyclooxygenase enzymes (COX-1 and COX-2) are candidate neuroinflammatory mediators that may contribute to the HI-induced demise of early oligodendrocyte progenitors and myelination. We investigated whether ibuprofen, a non-steroidal anti-inflammatory drug that inhibits COX enzymes, can attenuate neuroinflammation and associated white matter damage incurred in a rodent model of preterm HI. On postnatal day 3 (P3), HI was produced (right carotid artery ligation and 30 min 6% O(2)). An initial dose of ibuprofen (100mg/kg, s.c.) was administered 2h after HI followed by a maintenance dose (50mg/kg, s.c.) every 24h for 6 days. Post-HI ibuprofen treatment significantly attenuated the P3 HI-induced increases in COX-2 protein expression as well as interleukin-1beta (IL-1ß) and tumour necrosis factor-alpha (TNF-α) levels in the brain. Ibuprofen treatment also prevented the HI-induced loss O4- and O1-positive oligodendrocyte progenitor cells and myelin basic protein (MBP)-positive myelin content one week after P3 HI. These findings suggest that a repeated, daily, ibuprofen treatment regimen administered after an HI insult may be a potential therapeutic intervention to prevent HI-induced damage to white matter progenitors and early myelination in the preterm neonate.

Efficacy of post-insult minocycline administration to alter long-term hypoxia-ischemia-induced damage to the serotonergic system in the immature rat brain.

Neuroinflammation is a key mechanism contributing to long-term neuropathology observed after neonatal hypoxia-ischemia (HI). Minocycline, a second-generation tetracycline, is a potent inhibitor of neuroinflammatory mediators and is successful for at least short-term amelioration of neuronal injury after neonatal HI. However the long-term efficacy of minocycline to prevent injury to a specific neuronal network, such as the serotonergic (5-hydroxytryptamine, 5-HT) system, is not known. In a post-natal day 3 (P3) rat model of preterm HI we found significant reductions in 5-HT levels, 5-HT transporter expression and numbers of 5-HT-positive dorsal raphé neurons 6 weeks after insult compared to control animals. Numbers of activated microglia were significantly elevated in the thalamus and dorsal raphé although the greatest numbers were observed in the thalamus. Brain levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were also significantly elevated on P45 in the thalamus and frontal cortex. Post-insult administration of minocycline for 1 week (P3-P9) attenuated the P3 HI-induced increases in numbers of activated microglia and levels of TNF-α and IL-1ß on P45 with concurrent changes in serotonergic outcomes. The parallel prevention of P3 HI-induced serotonergic changes suggests that inhibition of neuroinflammation within the first week after P3 HI injury was sufficient to prevent long-term neuroinflammation as well as serotonergic system damage still evident at 6 weeks. Thus early, post-insult administration of minocycline may target secondary neuroinflammation and represent a long-term therapy to preserve the integrity of the central serotonergic network in the preterm neonate.