Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative motor neuron disease (MND) with heterogeneity in disease onset, progression and treatment response. The Strategic ALS Australia–Systems Genomics Consortium (SALSA-SGC) was established in recognition of the need for large data sets of clinical data matched with biological samples to enable and foster ALS research and better understanding of aetiology and biological mechanisms. SALSA-SGC brought together the major Australian MND clinics to set up sustainable infrastructure that could facilitate long-term human ALS research and clinical trials nationally and internationally.

Between April 2016 and December 2024, SALSA-SGC recruited 1813 participants, including 1386 ALS/MND cases, 388 controls and 39 others (asymptomatic relatives and ALS mimics). Clinical data and biospecimens are available for 1333 and 1189 ALS cases, respectively, with longitudinal data spanning 4442 total clinic visits and 3201 samples. An open-access online data explorer showcases collected datasets.

Detailed clinical and questionnaire data allow an in-depth description of the cohort, informing clinical and health policy research. Screening for known ALS large-effect risk variants identified 125 mutation carriers (11.5% from N=1059), including 70 with C9orf72 expansions. Single Nucleotide Polymorphism (SNP)-array data (N=1088 cases; N=244 controls) have supported multiple published studies. SALSA-SGC resources are actively used by national and international researchers.

Ongoing efforts aim to expand recruitment into regional Australia and enhance sample processing for cell-based studies. The SALSA-SGC resource is accessible by researchers under agreements governed by participant consent, human ethics committee guidelines and agreed use of data and samples.

To collate and appraise evidence from existing systematic reviews and meta-analyses on interventions to prevent stillbirth and reduce perinatal mortality across the reproductive continuum, including preconception, antenatal, intrapartum and immediate newborn periods.

Umbrella review synthesising evidence from systematic reviews, including meta-analyses where available.

A comprehensive search was conducted in CENTRAL (via Cochrane Register of Studies Online), PubMed, Embase and Web of Science, along with trial registries (WHO International Clinical Trials Registry Platform, ClinicalTrials.gov and ISRCTN Registry), from inception to 12 January 2026.

Systematic reviews and meta-analyses synthesising randomised controlled trials or quasi-experimental studies that reported stillbirth, perinatal mortality, fetal loss or fetal death were included. Reviews focused exclusively on predefined high-risk populations were excluded.

Two reviewers independently extracted data and assessed methodological quality using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). Grading of Recommendations, Assessment, Development and Evaluation (GRADE) certainty ratings were extracted as reported by the original review authors. Evidence synthesis followed a structured framework adapted from Ota et al, integrating direction of effect and certainty of evidence based on pooled estimates and GRADE assessments. Publication overlap was assessed using the Corrected Covered Area index where relevant.

A total of 116 systematic reviews were included, synthesising evidence from randomised controlled and quasi-experimental studies across preconception, antenatal, intrapartum and immediate newborn periods. Evidence from individual reviews showed clear benefit for several interventions, including balanced energy-protein supplementation, home visits by community health workers, birth preparedness interventions, labour induction at or beyond 37 weeks of gestation and skilled or community-based intrapartum care, primarily for reducing perinatal mortality. Reduced antenatal visit schedules compared with standard care were associated with a possible increase in stillbirth or perinatal mortality, indicating potential harm. Many interventions—such as group antenatal care (ANC), nutritional education, case-note provision, routine ultrasound or Doppler monitoring, antibiotic treatment for bacterial vaginosis, antiretroviral therapy in pregnancy and several pharmacological or hormonal interventions—demonstrated unknown or inconclusive effects on stillbirth or perinatal mortality, largely due to imprecision and heterogeneity.

This umbrella review identifies a range of interventions with evidence of effectiveness across the reproductive continuum, particularly those addressing maternal nutrition, continuity of ANC and quality intrapartum and newborn care. However, substantial evidence gaps remain, especially for interventions widely implemented without strong supporting evidence. These findings highlight the need for context-specific implementation research and prioritisation of proven strategies in low- and middle-income countries, where the burden of stillbirth remains highest.

CRD42024531100.