Katie. M. Groom

Background: Transabdominal cervical cerclage (TACC) may be used for those at very high risk of spontaneous preterm birth, where transvaginal cerclage has been ineffective previously or is not possible. High‐quality randomised evidence supports the use of this relatively uncommon procedure, but there is no published experience of its use in Aotearoa New Zealand. Aims: To review all cases of TACC performed in a tertiary hospital that receives referrals from across Aotearoa New Zealand. Materials and Methods: This is a single‐centre retrospective observational study. All TACC performed at National Women's Health, Auckland City Hospital, Auckland between 1st January 2007 and 31st August 2023 were included. Cases were identified from hospital theatre records. Data were obtained from medical records and perinatal databases. Outcomes for the index and all subsequent births up to 31st October 2024 were included. Results: Forty people received a TACC. The most common indication was obstetric history (27, 62.5%), followed by extensive cervical surgery (13, 32.5%). There were 47 pregnancies in 33 people, including five early miscarriages and one pregnancy termination for foetal anomalies. In the remaining 41 pregnancies, 37 (90.2%) resulted in a live birth ≥ 24 weeks, with a mean gestation at birth of 36 + 1 weeks. All 37 neonates were alive at hospital discharge with low rates of complications. Conclusions: This study demonstrates favourable perinatal outcomes following TACC in those at high risk of spontaneous preterm birth in Aotearoa New Zealand.

Background: Phosphodiesterase type 5 (PDE-5) inhibitors have been proposed as a potential in-utero treatment to improve uteroplacental perfusion in pregnancies with fetal growth restriction. Randomized controlled trials (RCTs) have shown conflicting results, with concerns about the integrity of several trials. Objective: This protocol outlines a systematic review and aggregate data meta-analysis of RCTs investigating the short-term effects of PDE-5 inhibitors versus placebo or no treatment in pregnancies affected by FGR. We will assess the trustworthiness and scientific integrity of included trials and evaluate their impact on pooled outcomes. Methods: Eligible trials were identified through a literature search. Primary outcome is mortality (stillbirth, neonatal or infant death). Secondary outcomes include severe neonatal morbidities and maternal preeclampsia. Risk of bias will be assessed using the Cochrane Risk of Bias 2 tool. Trustworthiness will be evaluated using the INSPECT-SR tool, the Cochrane Pregnancy and Childbirth Trustworthiness Screening Tool and additional statistical analyses. In the aggregate data meta-analysis, trials will be classified into subgroups based on the results from the INSPECT-SR tool. If concerns about trial conduct or reporting arise, authors will be contacted; unresolved issues may be referred to the journal. Discussion: This review will critically assess the trustworthiness of randomized trials on PDE-5 inhibitors for FGR and summarize the available evidence. This protocol is written in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines ¹ . Corresponding PRISMA-P items are indicated in brackets following each section heading.

Background: Preterm birth is a priority area for practice improvement internationally. Clinical practice guidelines improve the efficiency of clinical decision‐making and, when implemented effectively, may advance the quality and consistency of care. Guideline implementation tools may help to further optimise the use of guidelines. Objectives: To determine if guideline implementation tools improve adherence to preterm birth guideline recommendations and have an impact on differences seen by ethnicity. Search Strategy: Systematic search of MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials and Scopus on 11 December 2023. Selection Criteria: Eligibility criteria included randomised and non‐randomised studies that used an implementation tool and measured adherence to a guideline on preterm birth. Data Collection and Analysis: Data were extracted including study details and ethnicity as an equity consideration. Meta‐analyses were performed on adherence to preterm birth guideline recommendations with planned subgroup analysis by ethnicity/Indigeneity and topic of guideline. Main Results: Twenty studies were included; two cluster randomised controlled trials and 18 before–after studies. Nineteen studies comparing guideline implementation tool to no tool reported improved adherence to guideline recommendations with the use of a tool (data for meta‐analysis from 14 studies, 20 961 people, OR 13.8, 95% CI 6.02–31.71, adherence in 3871/11 195 [34.6%] before compared with 6607/9766 [67.6%] after). Only one study performed analysis by ethnicity. Conclusions: Effective implementation tools have the potential to increase adherence to evidence‐based preterm birth guidelines, improving quality and consistency of preterm birth care.

Background: The human placenta releases large numbers of extracellular vesicles (EVs) into the maternal circulation throughout pregnancy. In preeclampsia, a hypertensive disorder of pregnancy, the number of EVs increases and the cargo they carry is altered. We investigated whether human placental EVs from pregnancies complicated by preeclampsia directly alter maternal vascular function, a hallmark of the disorder, and if EVs from early-onset or late-onset variants of preeclampsia have different effects on the vasculature. Methods: Macro-EVs, micro-EVs and nano-EVs were isolated from cultured explants of human placentae from women with early-onset or late-onset preeclampsia, or from normotensive women. EVs were injected intravenously into pregnant mice and either at 30 minutes or 24 hours after injection, the mice were euthanized and the function of second order mesenteric arteries were assessed using wire myography. Results: Placental EVs from pregnancies with early-onset preeclampsia enhanced vasoconstriction to PE, AngII, and ET-1 whilst impairing vasodilation to ACh and SNP in a time-dependent fashion, most prominently at 24 hours. In contrast, placental EVs from pregnancies with late-onset preeclampsia induced few differences compared to arteries taken from control mice injected with EVs from women with normotensive pregnancies. Conclusions: To the best of our knowledge, this is the first comparison of vascular function after exposure to the full range of EVs produced by placentae from women with early-onset and late-onset preeclampsia and normotensive women. Placental EVs from early-onset preeclampsia demonstrated the ability to contribute to the development of the high-resistance haemodynamic profiles of women affected by early-onset preeclampsia.

In this follow-up at 2.5 years of children from the STRIDER NZAus Trial (N = 112), in which women with singleton pregnancies affected by severe early fetal growth restriction were randomized to sildenafil citrate 75 mg daily or placebo until 32 weeks, there was no difference between groups in survival without neurosensory impairment, defined as any of cerebral palsy, deafness, blindness, cognitive delay (Bayley III cognition or language score >1 SD below mean) or motor delay: 30/56[54%] vs. 34/56[61%]; aOR = 0.74, 95%CI: 0.31, 1.77. However, children exposed to sildenafil appeared to be more likely to have cognitive delay (13/45[29%] vs. 4/40[10%]; aOR = 3.71, 95% CI: 1.01, 13.63) but less likely to have emotional-behavioural difficulties (2/43[5%] vs. 8/38[21%]; aOR = 0.19, 95%CI: 0.03, 1.00). Conclusion: maternal sildenafil treatment for severe early-onset FGR was not associated with altered survival free of neurosensory impairment at 2.5 years’ corrected age.

Background: Clinical trial evidence underpins evidence-based medicine and the improvement of healthcare worldwide. In Australasia, a significant proportion of clinical trials are conducted by geographically dispersed and multidisciplinary clinical researchers under the auspices of Clinical Trials Networks (CTNs). These groups play an important role in contributing to evidence-based medicine, primarily by conducting investigator-initiated clinical trials. Despite their clear benefits in terms of return on investment, CTNs suffer significant challenges. Methods: We conducted surveys and focus groups with Australian and New Zealand CTNs to identifying the activities and attributes that enable CTNs to operate successfully. Based on our findings, we then conducted further surveys of Australian and New Zealand CTNs to identify the prevalence of these success factors in existing CTNs. Results: Our focus groups identified three key themes associated with success and growth of a CTN: engaged membership, established infrastructure, and sustainability; and thirteen critical success factors: shared vision and motivation; strong leaders, governance and succession planning; an executive officer; sustainable funding for operations; effective communication; diverse representation and consumer input; transparent processes; a strong pipeline of trials; a reputable and recognised CTN brand; innovation and adaption; an effective group of network sites with a skilled workforce; embedded trials and prioritisation of research. These key themes and the relevant key areas were presented to 30 CTNs. Two factors were almost universally present in CTNs, reflecting the importance of these attributes: the presence of an executive officer, and a strong pipeline of trials. Three factors had a particularly low prevalence: sustainable funding for operations, effective communication, and embedded trials. Conclusions: By supporting both emerging and established CTNs to achieve critical success factors, we can improve the efficiency of CTNs to continue to contribute and expand their clinical trial activities. Particular focus needs to be on finding sustainable funding for CTNs, and raising awareness of the critical role undertaken by CTNs to improve healthcare and health outcomes.