Andrew K. Ewer

Pulse oximetry screening (POS) is a simple non-invasive tool which enables the early detection of critical congenital heart defects (CCHDs). POS has moderate sensitivity and high specificity; it is cost-effective, readily accepted by parents and healthcare professionals, and its introduction significantly reduces mortality from CCHDs. As a result, most high-income countries and many middle-income countries have introduced, or are considering introducing, POS. Despite the international uptake of POS, there is still no consensus regarding the most appropriate screening algorithm, although several have been described. In addition, this review will consider the variations—and their relative advantages and disadvantages—between POS algorithms and also explore how modifications to existing algorithms—such as the addition of a perfusion index or the incorporation of machine learning—may have the potential to improve future detection of CCHDs.

Background: Optimal oxytocin dosing during induction of labour remains uncertain despite widespread use. We aimed to determine whether a high-dose oxytocin regimen reduced caesarean section rates without increasing maternal or neonatal morbidity compared with a standard-dose regimen in nulliparous women. Methods: We performed a multicentre, randomised, parallel-group, double-blind controlled trial across 16 UK maternity units, including nulliparous women undergoing induction of labour requiring oxytocin after rupture of membranes. Participants were randomly assigned (1:1) to receive either high-dose oxytocin (starting 4 mU/min, titrated to a maximum dose of 64 mU/min) or standard-dose oxytocin (starting 2 mU/min, titrated to a maximum dose of 32 mU/min). The primary outcome was caesarean section. The trial is registered at the ISRCTN registry, ISRCTN79220656. Findings: Between May 31, 2022, and Sept 7, 2025, 976 women were randomised to high-dose (n=489) or standard-dose oxytocin (n=487). Following a futility analysis requested by the Data Monitoring Committee, recruitment stopped prematurely because of low probability of benefit with high-dose. Caesarean section occurred in 218 (45%) of 489 participants in the high-dose group and 193 (40%) of 487 participants in the standard-dose group (adjusted risk ratio 1· 14, 95% CI 0·99 to 1·32; adjusted risk difference 0·05, 95% CI 0·01 to 0·11; p=0·08). Total dose received was 47% higher in the high-dose group (10·3 mU/min v 7·0 mU/min). Uterine tachysystole was more common with high-dose (208 [43%] versus 167 [35%]; adjusted risk ratio 1·21, 95% CI 1·03 to 1·41; adjusted risk difference 0·10, 95% CI 0·04 to 0·16). Maternal and neonatal outcomes and serious adverse events were similar between groups, with 960 babies discharged home with mother. Interpretation: A high-dose oxytocin regimen, compared to standard-dose for induction of labour did not reduce caesarean section rates. High-dose oxytocin should not be used.

Background: Delay in the first stage of labour occurs in approximately 20% of nulliparous women. Recommended treatment is intravenous oxytocin, which shortens labour but does not affect the mode of birth. There is some evidence that a higher dose regimen may decrease the need for caesarean section. Objective: The primary objective was to establish if a high-dose regimen of oxytocin compared to the current standard-dose regimen reduced the need for caesarean section for nulliparous women with confirmed delay in the first stage of labour. Design: Multicentre, randomised double-blind controlled trial. Setting: Twenty-one maternity units in the United Kingdom. Participants: Consenting nulliparous women who had a singleton cephalic pregnancy, gestation of 37–41 weeks inclusive, confirmed delay in labour in first stage, ruptured membranes and for whom the clinical decision has been made to prescribe oxytocin. Interventions: Standard-dose regimen of oxytocin (2 mU/min increasing every 30 minutes to a maximum of 32 mU/min) compared with high-dose regimen (4 mU/min increasing every 30 minutes to a maximum of 64 mU/min). Main outcome measures: The primary outcome was the rate of caesarean section. Secondary outcomes included maternal and neonatal birth outcomes and safety. Results: One hundred and eighteen women were successfully randomised via third-party minimisation from an intended sample size of 1500 between 30 June 2017 and 14 November 2022. The caesarean section rate in the standard-dose group was 34% (20/58) and 27% (16/60) in the high-dose group. The intervention was provided as intended in 96% (113/118) of participants. There was no obvious suggestion that the high-dose regime was unsafe (all neonates were discharged home with mother), but this size of sample prohibited any definitive conclusions. Limitations: The trial did not meet its intended sample size due to a number of challenges. It was difficult for busy clinical staff to recruit women in labour in this acute, but not emergency, situation. The legislative requirements of undertaking research using interventional medicinal products imposed further constraints, and we encountered challenges in the production, blinding and monitoring required. Changes in clinical practice since trial design and commencement 10 years ago have resulted in fewer women going into spontaneous labour (reduced from 66% to 47%), and therefore potentially becoming eligible, due to more women having labour induced (22%–33%) or elective caesarean sections (12%–20%). These challenges were further compounded by a falling birth rate and the impact of the COVID-19 pandemic. Conclusions: The question of the optimum dose of oxytocin for nulliparous women delayed in the first stage of spontaneous labour remains an important unanswered clinical question, and the major challenge is how best to address this within the current regulatory framework. Future work: Future studies should consider whether the option of delayed consent would be suitable in this acute, but not emergency, situation. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 14/140/44.

Background: Second trimester miscarriage and preterm birth is a significant global problem. Surgical cervical cerclage is performed to prevent pregnancy loss and preterm birth. It utilises either a monofilament or braided suture. It is hypothesised that a braided material becomes colonised with pathogenic bacteria that causes vaginal dysbiosis, infection and cerclage failure. Objectives: The primary objective of the study was to examine the effectiveness of using a monofilament suture material as opposed to a braided suture material on pregnancy loss in women requiring a vaginal cervical cerclage. Design: Superiority open randomised controlled trial. Setting: Seventy-five maternity sites across the UK. Participants: Women experiencing a singleton pregnancy requiring a cervical cerclage. Interventions: Monofilament suture or braided suture. Main outcome measures: The primary outcome was pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life). Secondary outcomes included the core outcome set for preterm birth. Methods: Women were randomised on a 1 : 1 basis to monofilament or braided cerclage utilising a bespoke randomisation service with minimisation dependent on the site, indication for cerclage, intention to use progesterone and planned surgical technique. The inclusion criteria were three or more previous mid-trimester losses or preterm births, insertion of a cerclage in a previous pregnancy, a history of a mid-trimester loss or preterm birth with a shortened cervical length in the current pregnancy or in women who clinicians deemed at risk of preterm birth. The exclusion criteria were an emergency or rescue cerclage, age of < 18 years, being unable to give informed consent or the cerclage having to be placed abdominally. The original sample size was calculated based on a relative risk reduction of 41% from a pregnancy loss rate of 19% in the braided group to 11% in the monofilament group with 90% power and alpha at p = 0.05. The independent data monitoring committee noted a lower-than-anticipated pooled event rate within the trial and recommended an increase in sample size to 2050. The outcome data were collected using clinical record forms from the maternal and neonatal medical records and reported to Birmingham Clinical Trials Unit. Results: A total of 2049 women were randomised, after withdrawals and loss to follow-up, data on 1005 women in the monofilament group and 993 women in the braided group were included. The baseline demographics between the groups were similar. There was no evidence of a difference in pregnancy loss rates between the monofilament and braided groups (80/1003 vs. 75/993; adjusted risk ratio: 1.05, 95% confidence interval: 0.79 to 1.40; adjusted risk difference: 0.002, 95% confidence interval: −0.02 to 0.03). Limitations: The trial did not collect long-term paediatric outcomes. There were no safety concerns. Conclusions: There was no evidence of a difference in pregnancy loss between a monofilament suture and a braided suture. Future work: Long-term follow-up of neonates born within the C-STICH (cerclage suture type for an insufficient cervix and its effects on health outcomes) trial. Trial registration: This trial is registered as ISRCTN15373349. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/04/107) and is published in full in Health Technology Assessment; Vol. 28, No. 40. See the NIHR Funding and Awards website for further award information.

Background Perinatal advance care planning (PnACP) is a process of formal decision-making to help families plan for their baby’s care when recognised that they may have a life-limiting condition. While PnACP is recommended in policy, there is a lack of evidence to support implementation and development in the perinatal setting. Objective To conduct an online survey of UK and Ireland perinatal providers to examine how PnACP is operationalised in current practice. Methods A secure online questionnaire was developed to collect data on (1) ‘what’ is being implemented, (2) the ‘processes’ being used, (3) perceived impact and (4) unmet support needs. Data were analysed using basic descriptive statistics, thematic analysis and through a conceptual lens of Normalisation Process Theory. Results Questionnaires were completed by 108 health professionals working in 108 maternity and neonatal services, representing 90 organisations across the UK and Ireland. This revealed many resources and examples of good practice to support PnACP. However, there was wide variation in how PnACP was conceptualised and implemented. Existing frameworks, pathways and planning tools are not routinely embedded into care, and respondents identified many barriers that negatively impact the quality of care. They called for better integration of palliative care principles into acute settings and more investment in staff training to support families at existentially difficult times. Conclusions Priorities for additional perinatal service development include greater sharing of best practice and effective strategies to target the unique challenges of PnACP, such as time-sensitive collaborative working and decision-making in the face of high uncertainty.

Objective To determine the impact of supplemental bovine lactoferrin on the gut microbiome and metabolome of preterm infants. Design Cohort study nested within a randomised controlled trial (RCT). Infants across different trial arms were matched on several clinical variables. Bacteria and metabolite compositions of longitudinal stool and urine samples were analysed to investigate the impact of lactoferrin supplementation. Setting Thirteen UK hospitals participating in a RCT of lactoferrin. Patients 479 infants born Results 10 990 stool and 22 341 urine samples were collected. Analyses of gut microbiome (1304 stools, 201 infants), metabolites (171 stools, 83 infants; 225 urines, 90 infants) and volatile organic compounds (314 stools, 117 infants) were performed. Gut microbiome Shannon diversity at 34 weeks corrected age was not significantly different between infants in the lactoferrin (mean=1.24) or placebo (mean=1.06) groups (p=0.11). Lactoferrin receipt explained less than 1% variance in microbiome compositions between groups. Metabolomic analysis identified six discriminative features between trial groups. Hospital site (16%) and postnatal age (6%) explained the greatest variation in microbiome composition. Conclusions This multiomic study identified minimal impacts of lactoferrin but much larger impacts of hospital site and postnatal age. This may be due to the specific lactoferrin product used, but more likely supports the findings of the RCT in which this study was nested, which showed no impact of lactoferrin on reducing rates of sepsis. Multisite mechanistic studies nested within RCTs are feasible and help inform trial interpretation and future trial design.

Dear Editor, The ichthyoses are rare disorders characterized by thick, scaly skin. The commonest neonatal type, autosomal recessive congenital ichthyosis (ARCI), is genetically heterogeneous,¹ with prognoses ranging from neonatal death to rapid spontaneous resolution. ARCI usually presents as collodion membrane (CM), and rarely harlequin ichthyosis (HI). This common neonatal phenotype and uncertain prognosis present challenges for neonatologists, with a risk of iatrogenic complications from overtreatment. Recommendations for managing HI and CM are generic, based on more severe cases, and include intensive monitoring in a humidified incubator.² By contrast, the authors’ experience is that babies with uncomplicated CM can be nursed successfully in an open cot with minimal monitoring, facilitating skincare, parental bonding and early discharge from hospital.