Cerclage suture type to prevent pregnancy loss in women requiring a vaginal cervical cerclage: the C-STICH RCT.

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.

Cervical cerclage is an operation performed in pregnancy to prevent miscarriage and preterm birth. A cervical cerclage is sometimes recommended in women who have had babies born prematurely before or who have had previous cervical surgery. A cerclage operation involves a stitch being inserted around the neck of the womb (cervix) to keep it closed during pregnancy and to prevent it opening prematurely. When performing the operation, the doctor can use different types of threads made of different materials. The threads used to perform the operation are called sutures. One suture type is a single strand or monofilament thread, and the other is a multifilament braided thread with lots of thin strands woven together. Some evidence has suggested that using a monofilament suture thread prevented pregnancy loss by preventing infection. Therefore, we performed a randomised controlled trial of the use of monofilament suture thread versus braided suture thread, aiming to reduce pregnancy loss in women who were having a cerclage as part of their routine care. The women consented to take part in the study and were randomly allocated to their cerclage performed with either a monofilament or braided suture thread; there was no other change to their planned pregnancy care. What happened in their pregnancy was recorded from their medical records and analysed. A total of 2049 women agreed to take part in the study and consented to the analysis of their pregnancy and neonatal outcomes. Cerclage suture type for an insufficient cervix and its effects on health outcomes showed that there was no difference in pregnancy loss between the two suture threads. There was decreased maternal sepsis and decreased chorioamnionitis (which is an infection inside the womb during labour) in the women who received a monofilament suture, which needs further investigation. Although more women who had a cerclage using the monofilament thread needed a small operation and an anaesthetic, often between 36 and 37 weeks, to remove the monofilament suture prior to a vaginal birth, there were no differences in the outcomes for their babies.

Pulse Oximetry Screening for Critical Congenital Heart Defects in Newborn Babies.

Pulse oximetry screening (POS) was first described over 20 years ago. However, in recent years, major clinical trials have demonstrated consistent test accuracy for the detection of critical congenital heart defects (CCHD). International uptake of POS has progressed well over the last 10 years with most major high-income countries now recommending screening. This review describes the evidence base which has led to this, the current debate regarding choice of screening algorithm, and the future areas for further research.

Advance care planning in perinatal settings: national survey of implementation using Normalisation Process Theory.

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.

Mechanisms affecting the gut of preterm infants in enteral feeding trials: a nested cohort within a randomised controlled trial of lactoferrin.

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 <32 weeks' gestation between June 2016 and September 2017. 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.

Monofilament suture versus braided suture thread to improve pregnancy outcomes after vaginal cervical cerclage (C-STICH): a pragmatic randomised, controlled, phase 3, superiority trial.

BACKGROUND: Miscarriage in the second trimester and preterm birth are significant global problems. Vaginal cervical cerclage is performed to prevent pregnancy loss and preterm birth. We aimed to determine the effectiveness of a monofilament suture thread compared with braided suture thread on pregnancy loss rates in women undergoing a cervical cerclage. METHODS: C-STICH was a pragmatic, randomised, controlled, superiority trial done at 75 obstetric units in the UK. Women with a singleton pregnancy who received a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were centrally randomised (1:1) using minimisation to receive a monofilament suture or braided suture thread for their cervical cerclage. Women and outcome assessors were masked to allocation as far as possible. The primary outcome was pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life, analysed in the intention-to-treat population (ie, all women who were randomly assigned). Safety was also assessed in the intention-to-treat population. The trial was registered with ISRCTN, ISRCTN15373349. FINDINGS: Between Aug 21, 2015, and Jan 28, 2021, 2049 women were randomly assigned to receive a monofilament suture (n=1025) or braided suture (n=1024). The primary outcome was ascertained in 1003 women in the monofilament suture group and 993 women in the braided suture group. Pregnancy loss occurred in 80 (8·0%) of 1003 women in the monofilament suture group and 75 (7·6%) of 993 women in the braided suture group (adjusted risk ratio 1·05 [95% CI 0·79 to 1·40]; adjusted risk difference 0·002 [95% CI -0·02 to 0·03]). INTERPRETATION: Monofilament suture did not reduce rate of pregnancy loss when compared with a braided suture. Clinicians should use the results of this trial to facilitate discussions around the choice of suture thread to optimise outcomes. FUNDING: National Institute of Health Research Health Technology Assessment Programme.

Left Ventricular Dysfunction Persists in the First Week after Re-Warming following Therapeutic Hypothermia for Hypoxic-Ischaemic Encephalopathy.

OBJECTIVES: The aim of this study was to assess serial myocardial function in newborn infants receiving therapeutic hypothermia (TH) as treatment for moderate to severe hypoxic-ischaemic encephalopathy (HIE). METHODS: Serial echocardiography was performed in 20 term infants receiving TH on days 1-3 and again after re-warming. Left ventricular (LV) fractional shortening, LV cardiac output, and tissue Doppler imaging-derived myocardial velocities and myocardial performance index were measured. Similar assessments were obtained from 20 well term infants within 48 h of birth. RESULTS: LV fractional shortening (LVFS) was similar between cases and controls during all measurements (25.3% vs. 27.4%). The mean LV cardiac output on day 1 was significantly lower in cases (109 mL/kg/min) than in controls (162 mL/kg/min) but increased after re-warming (145 mL/kg/min). All myocardial velocities were significantly lower in cases on day 1, increased during TH, but LV indices remained consistently lower compared to controls even after re-warming. LV myocardial performance index was higher in cases compared to controls on day 1, improved during TH but remained abnormal after re-warming. The right ventricular myocardial performance index was similar between cases and controls. CONCLUSION: Among infants affected by moderate to severe HIE, LV function appears to be more affected than right ventricular function with LV dysfunction persisting after completion of TH. LVFS was not useful to determine dysfunction in this cohort.

Busy can be happy: 'Cake Thursday' as a team bonding exercise.

Implementation of 'Cake Thursday' as a team bonding and morale-boosting exercise.

Temporal trends in routine predischarge pulse oximetry screening: 6 years' experience in a UK regional neonatal unit.

OBJECTIVES: To evaluate the continued impact of pulse oximetry screening (POS) in a regional neonatal unit (NNU) and identify trends in screening outcomes in comparison with our previous experience. DESIGN: Retrospective review of admissions between April 2013 and March 2019 (the current study) and comparison with previously published data (the 2014 study). PATIENTS: All infants >34 weeks completed gestation admitted to NNU as a result of positive POS. OUTCOME MEASURES: Indication for admission, diagnosis, investigations and management. RESULTS: There were 49 375 livebirths and 253 NNU admissions as a result of positive POS (0.5% of livebirths; compared with 0.8% in 2014). 247/253 (97.6%) of those admitted had a significant diagnosis requiring medical intervention (compared with 79% in 2014) and the proportion of healthy babies (with transitional circulation) admitted decreased from 21% to 2.4%.22 (9%) babies admitted as a result of a positive POS were found to have a previously undiagnosed congenital heart defect (CHD) of which eight were critical CHDs (CCHDs). This accounted for 73% of all undiagnosed CCHD undergoing POS. The antenatal detection rate of CCHD was 75% compared with 46% in 2014. No baby died or collapsed on the postnatal ward during the study period. The proportion of babies with CCHD identified before discharge improved from 94% to 99%. CONCLUSIONS: Routine POS, in addition to antenatal screening and postnatal examination, continues to contribute to the improvement of our overall CCHD detection rates. We have demonstrated an overall reduction in the admission of healthy babies and therefore workload following a positive test.

C-STICH: Cerclage Suture Type for an Insufficient Cervix and its effect on Health outcomes-a multicentre randomised controlled trial.

BACKGROUND: Preterm birth is associated with significant mortality and morbidity for mothers and babies. Women are identified as high risk for preterm birth based on either previous medical/pregnancy history or on ultrasound assessment of the cervix. Women identified as high risk can be offered a cervical cerclage (a purse string stitch) around the cervix (neck of the womb) to reduce the risk of preterm birth. In women who have a cervical cerclage, the procedure can be performed using either a monofilament (single-stranded) or braided (woven) suture material. Both suture materials are routinely used for cervical cerclage and there is uncertainty as to which is superior. METHODS: A multicentre, open, randomised controlled superiority trial of 2050 women presenting at obstetric units, deemed to be at risk of preterm birth and already scheduled to have a cervical cerclage as part of their standard care. Inclusion criteria include singleton pregnancies and an indication for cervical cerclage for either a history of three or more previous mid-trimester losses or premature births (≤ 28 weeks), insertion of cervical sutures in previous pregnancies, a history of mid trimester loss or premature birth with a (current) shortened (≤ 25 mm) cervix, or women whom clinicians deem to be at risk of preterm birth either by history or the results of an ultrasound scan. Exclusion criteria include women who have taken part in C-STICH previously, are aged less than 18 years old at the time of presentation, require a rescue cerclage, and are unwilling or unable to give informed consent and in whom a cerclage will be placed by any route other than vaginally (e.g. via an abdominal route). Following informed consent, women are randomised on a 1:1 basis to either monofilament or braided suture, by minimisation. The primary outcome is pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life), and secondary outcomes include the core outcome set for preterm birth trials. DISCUSSION: Optimising established interventions to prevent preterm birth is important in reducing perinatal mortality rates. TRIAL REGISTRATION: ISRCTN 15373349 . Registered before recruitment on 03 December 2014 prior to first recruit.

New born pulse oximetry screening: A global perspective.

The possibility of pulse oximetry screening (POS) for congenital heart defects was first described over 20 years ago. Since then, an accumulation of research evidence and clinical practice experience has established POS as an important test to detect critical congenital heart defects (CCHDs). POS meets the criteria for universal screening and professional bodies around the globe have recommended universal POS. Many countries have already adopted POS while several others are working towards its implementation. In low and low-middle-income countries (LLMIC), POS has the additional potential for reducing morbidity and mortality from neonatal sepsis. This review summarises the evidence for POS and looks at current global uptake and different approaches to the implementation of POS.

Fetal ultrasound diagnosis allows effective early postnatal treatment of hematometrocolpos.

Fetal hematometrocolpos is a rare finding with an incidence of 1 in 16 000 female births. We present a case of fetal hematometrocolpos managed exclusively by prenatal and postnatal ultrasound scans allowing for effective immediate postnatal surgical treatment.

Updated Strategies for Pulse Oximetry Screening for Critical Congenital Heart Disease.

Seven years after its addition to the US Recommended Uniform Screening Panel, newborn screening for critical congenital heart disease (CCHD) using pulse oximetry became mandatory in the United States. Although CCHD newborn screening reduces morbidity and mortality, there remain important opportunities to improve. An expert panel convened for a 1-day meeting in September 2018, including subject matter experts and representatives from stakeholder organizations. Presentations on CCHD outcomes, variations in approach to screening, and data and quality improvement helped identify improvement opportunities. The expert panel concluded that sufficient evidence exists to recommend modifying the current American Academy of Pediatrics algorithm by (1) requiring an oxygen saturation of at least 95% in both (formerly either) the upper and lower extremities to pass and (2) requiring only 1 repeat screen instead of 2 for cases that neither pass nor fail initially. The panel underscored the importance of improving public health reporting by further specifying the targets of screening and criteria for reporting outcomes (false-negative and false-positive cases). The panel also highlighted the need to ensure sufficient public health funding for CCHD newborn screening and opportunities for education and global implementation. Newborn screening for CCHD using pulse oximetry has led to significant improvements in child health outcomes. However, further important work is required to understand and improve the effectiveness and efficiency of screening.

Faecal volatile organic compounds in preterm babies at risk of necrotising enterocolitis: the DOVE study.

BACKGROUND: Early diagnosis of necrotising enterocolitis (NEC) may improve prognosis but there are no proven biomarkers. OBJECTIVE: To investigate changes in faecal volatile organic compounds (VOCs) as potential biomarkers for NEC. DESIGN: Multicentre prospective study. SETTINGS: 8 UK neonatal units. PATIENTS: Preterm infants <34 weeks gestation. METHODS: Daily faecal samples were collected prospectively from 1326 babies of whom 49 subsequently developed definite NEC. Faecal samples from 32 NEC cases were compared with samples from frequency-matched controls without NEC. Headspace, solid phase microextraction gas chromatography/mass spectrometry was performed and VOCs identified from reference libraries. VOC samples from cases and controls were compared using both discriminant and factor analysis methods. RESULTS: VOCs were found to cluster into nine groups (factors), three were associated with NEC and indicated the possibility of disease up to 3-4 days before the clinical diagnosis was established. For one factor, a 1 SD increase increased the odds of developing NEC by 1.6 times; a similar decrease of the two other factors was associated with a reduced risk (OR 0.5 or 0.7, respectively). Discriminant analyses identified five individual VOCs, which are associated with NEC in babies at risk, each with an area under the receiver operating characteristics curve of 0.75-0.76, up to 4 days before the clinical diagnosis was made. CONCLUSIONS: Faecal VOCs are altered in preterm infants with NEC. These data are currently insufficient to enable reliable cotside detection of babies at risk of developing NEC and further work is needed investigate the role of VOCs in clarifying the aetiology of NEC.