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.

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

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

Pathophysiological Mechanism of Extravasation via Umbilical Venous Catheters.

A rare complication of umbilical venous catheter (UVC) insertion is the extravasation of the infusate into the peritoneal cavity. We report 3 cases of abdominal extravasation of parenteral nutrition (PN) fluid via UVCs. Two of these cases presented as "acute abdomen" which were assumed to be necrotizing enterocolitis clinically; however, during postmortem, PN ascites and liver necrosis were found. A further case is described in an infant with congenital diaphragmatic hernia. While we were unable to ascertain direct vessel perforation by the catheter in any of these cases, based on pathological and histological examination, the proposed mechanism of PN fluid extravasation is leakage through microinjuries of liver vessel walls and necrotic parenchyma. PN extravasation should be considered as a differential diagnosis of acute abdomen when PN is infused via an UVC presumably as PN may have a direct irritant effect on the peritoneum.

Pulse oximetry screening for critical congenital heart defects.

BACKGROUND: Health outcomes are improved when newborn babies with critical congenital heart defects (CCHDs) are detected before acute cardiovascular collapse. The main screening tests used to identify these babies include prenatal ultrasonography and postnatal clinical examination; however, even though both of these methods are available, a significant proportion of babies are still missed. Routine pulse oximetry has been reported as an additional screening test that can potentially improve detection of CCHD. OBJECTIVES: • To determine the diagnostic accuracy of pulse oximetry as a screening method for detection of CCHD in asymptomatic newborn infants• To assess potential sources of heterogeneity, including:○ characteristics of the population: inclusion or exclusion of antenatally detected congenital heart defects;○ timing of testing: < 24 hours versus ≥ 24 hours after birth;○ site of testing: right hand and foot (pre-ductal and post-ductal) versus foot only (post-ductal);○ oxygen saturation: functional versus fractional;○ study design: retrospective versus prospective design, consecutive versus non-consecutive series; and○ risk of bias for the "flow and timing" domain of QUADAS-2. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2) in the Cochrane Library and the following databases: MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Health Services Research Projects in Progress (HSRProj), up to March 2017. We searched the reference lists of all included articles and relevant systematic reviews to identify additional studies not found through the electronic search. We applied no language restrictions. SELECTION CRITERIA: We selected studies that met predefined criteria for design, population, tests, and outcomes. We included cross-sectional and cohort studies assessing the diagnostic accuracy of pulse oximetry screening for diagnosis of CCHD in term and late preterm asymptomatic newborn infants. We considered all protocols of pulse oximetry screening (eg, different saturation thresholds to define abnormality, post-ductal only or pre-ductal and post-ductal measurements, test timing less than or greater than 24 hours). Reference standards were diagnostic echocardiography (echocardiogram) and clinical follow-up, including postmortem findings, mortality, and congenital anomaly databases. DATA COLLECTION AND ANALYSIS: We extracted accuracy data for the threshold used in primary studies. We explored between-study variability and correlation between indices visually through use of forest and receiver operating characteristic (ROC) plots. We assessed risk of bias in included studies using the QUADAS-2 tool. We used the bivariate model to calculate random-effects pooled sensitivity and specificity values. We investigated sources of heterogeneity using subgroup analyses and meta-regression. MAIN RESULTS: Twenty-one studies met our inclusion criteria (N = 457,202 participants). Nineteen studies provided data for the primary analysis (oxygen saturation threshold < 95% or ≤ 95%; N = 436,758 participants). The overall sensitivity of pulse oximetry for detection of CCHD was 76.3% (95% confidence interval [CI] 69.5 to 82.0) (low certainty of the evidence). Specificity was 99.9% (95% CI 99.7 to 99.9), with a false-positive rate of 0.14% (95% CI 0.07 to 0.22) (high certainty of the evidence). Summary positive and negative likelihood ratios were 535.6 (95% CI 280.3 to 1023.4) and 0.24 (95% CI 0.18 to 0.31), respectively. These results showed that out of 10,000 apparently healthy late preterm or full-term newborn infants, six will have CCHD (median prevalence in our review). Screening by pulse oximetry will detect five of these infants as having CCHD and will miss one case. In addition, screening by pulse oximetry will falsely identify another 14 infants out of the 10,000 as having suspected CCHD when they do not have it.The false-positive rate for detection of CCHD was lower when newborn pulse oximetry was performed longer than 24 hours after birth than when it was performed within 24 hours (0.06%, 95% CI 0.03 to 0.13, vs 0.42%, 95% CI 0.20 to 0.89; P = 0.027).Forest and ROC plots showed greater variability in estimated sensitivity than specificity across studies. We explored heterogeneity by conducting subgroup analyses and meta-regression of inclusion or exclusion of antenatally detected congenital heart defects, timing of testing, and risk of bias for the "flow and timing" domain of QUADAS-2, and we did not find an explanation for the heterogeneity in sensitivity. AUTHORS' CONCLUSIONS: Pulse oximetry is a highly specific and moderately sensitive test for detection of CCHD with very low false-positive rates. Current evidence supports the introduction of routine screening for CCHD in asymptomatic newborns before discharge from the well-baby nursery.

Newborn pulse oximetry screening in practice.

The concept of using pulse oximetry (PO) as a screening test to identify newborn babies with critical congenital heart defects (CCHD) before life-threatening collapse occurs has been debated for some time now. Several recent large studies have consistently shown that PO screening adds value to existing screening techniques with over 90% of CCHDs detected. It can also help identify newborn babies with low oxygen saturations due to infection, respiratory disease and non-critical CCHD. Many countries have now introduced PO screening as routine practice, and as screening gains more widespread acceptance in the UK, we have focused more on the practical aspects of screening in this article. This includes case reports to demonstrate how the different screening modalities for CCHD work together and the experience of hospitals that have already introduced PO screening programmes (Birmingham Women's Hospital and others). Issues discussed include how and when to screen babies in hospital, what to do with a positive screen and how to screen babies born at home. The UK National Screening Committee is currently investigating the potential feasibility of routine PO screening in the UK, and so it is perhaps a suitable time for individual hospitals to consider the possibility of introducing such screening in their maternity units.

Screening for Critical Congenital Heart Defects with Pulse Oximetry: Medical Aspects.

The detection of newborn babies with potentially life-threatening, critical congenital heart defects (CCHDs) before they collapse or expire remains an important clinical challenge. The absence of physical signs and the difficulty assessing mild cyanosis means that the newborn baby check misses up to a third of babies. Fetal anomaly ultrasound scanning identifies an increasing proportion, but this screen is operator-dependent and therefore highly variable; although some units report very high detection rates, overall most babies with CCHD are still missed. Pulse oximetry screening (POS) is an additional test that meets the criteria for universal screening. POS increases overall detection of CCHD to over 90% and also identifies babies with noncardiac, hypoxemic conditions (such as congenital pneumonia, early-onset sepsis, and pulmonary hypertension), which are usually included in the false positives. There is a wealth of published data on the POS, both in a research setting and more recently in routine clinical practice, and consideration of POS is becoming increasingly widespread particularly among high-income countries. But a degree of controversy still remains, and debate continues regarding the most appropriate time to screen, the most effective screening pathway, and screening outside the well-baby nursery. So, should all newborn babies be screened with POS, if so, when and where should screening take place, what saturations are acceptable, and which conditions are we trying to identify? This review will look at the available evidence and try to suggest the way forward for those considering its introduction into their clinical practice.

Assessment of myocardial function in preterm infants with patent ductus arteriosus using tissue Doppler imaging.

OBJECTIVE: To assess myocardial function in preterm infants with different degrees of ductal patency in the first week of life using tissue Doppler imaging. STUDY DESIGN: Infants <30 weeks of gestation underwent echocardiography on day 3. A total of 72 infants were recruited into the study and categorised into three groups (i) haemodyamically significant ductus arteriosus, (ii) patent ductus arteriosus and (iii) no patent ductus arteriosus. Those with haemodynamically significant ductus arteriosus were treated with indometacin and echocardiography was repeated after 48-72 hours following treatment. Peak systolic and diastolic myocardial velocities were obtained using tissue Doppler imaging, and myocardial performance index was calculated. RESULTS: Initial myocardial velocities were significantly lower and myocardial performance index significantly higher in the haemodynamically significant ductus arteriosus group compared with other groups. For the haemodynamically significant ductus arteriosus group, post-treatment myocardial velocities were higher and myocardial performance index lower than pre-treatment. CONCLUSION: Preterm infants with haemodynamically significant ductus arteriosus had lower myocardial velocities and higher myocardial performance index, suggesting relative systolic and diastolic myocardial dysfunction. Babies whose patent ductus arteriosus remained open despite indometacin had lower pre-treatment myocardial velocities and higher myocardial performance index than those babies whose patent ductus arteriosus closed, suggesting worse myocardial function in this group. Measurement of myocardial function using tissue Doppler imaging in preterm infants is feasible and may prove to be helpful in the management of babies with patent ductus arteriosus.

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.

Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis.

BACKGROUND: Screening for critical congenital heart defects in newborn babies can aid in early recognition, with the prospect of improved outcome. We assessed the performance of pulse oximetry as a screening method for the detection of critical congenital heart defects in asymptomatic newborn babies. METHODS: In this systematic review, we searched Medline (1951-2011), Embase (1974-2011), Cochrane Library (2011), and Scisearch (1974-2011) for relevant citations with no language restriction. We selected studies that assessed the accuracy of pulse oximetry for the detection of critical congenital heart defects in asymptomatic newborn babies. Two reviewers selected studies that met the predefined criteria for population, tests, and outcomes. We calculated sensitivity, specificity, and corresponding 95% CIs for individual studies. A hierarchical receiver operating characteristic curve was fitted to generate summary estimates of sensitivity and specificity with a random effects model. FINDINGS: We screened 552 studies and identified 13 eligible studies with data for 229,421 newborn babies. The overall sensitivity of pulse oximetry for detection of critical congenital heart defects was 76·5% (95% CI 67·7-83·5). The specificity was 99·9% (99·7-99·9), with a false-positive rate of 0·14% (0·06-0·33). The false-positive rate for detection of critical congenital heart defects was particularly low when newborn pulse oximetry was done after 24 h from birth than when it was done before 24 h (0·05% [0·02-0·12] vs 0·50 [0·29-0·86]; p=0·0017). INTERPRETATION: Pulse oximetry is highly specific for detection of critical congenital heart defects with moderate sensitivity, that meets criteria for universal screening. FUNDING: None.

Review of pulse oximetry screening for critical congenital heart defects in newborn infants.

PURPOSE OF REVIEW: The concept of using pulse oximetry as a screening method to detect undiagnosed critical congenital heart defects (CCHD) in asymptomatic newborns was first explored over 10 years ago. A number of studies were subsequently reported, which initially involved relatively small numbers of patients, low prevalence of CCHD and heterogeneous methodology. As a consequence, the majority of clinicians felt the case for routine pulse oximetry screening had not been proven. RECENT FINDINGS: In the last 3 years, four European studies reporting the test accuracy of routine pulse oximetry screening, and involving over 150 ,000 babies, have strengthened the argument. A systematic review and meta-analysis of almost 230 ,000 screened babies has also recently been published which reported high specificity, moderate sensitivity and a low false-positive rate. In addition, acceptability to parents and staff, cost-effectiveness and feasibility of implementing screening outside the research context have also been reported. SUMMARY: Pulse oximetry screening is a highly specific, moderately sensitive test, which is acceptable to parents and staff, likely to be cost-effective and fulfils the criteria for universal screening. Routine screening for CCHD using pulse oximetry is being increasingly supported and was added to the recommended uniform screening panel in the USA in 2011.

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.

Pulse oximetry screening for congenital heart defects in newborn infants (PulseOx): a test accuracy study.

BACKGROUND: Screening for congenital heart defects relies on antenatal ultrasonography and postnatal clinical examination; however, life-threatening defects often are not detected. We prospectively assessed the accuracy of pulse oximetry as a screening test for congenital heart defects. METHODS: In six maternity units in the UK, asymptomatic newborn babies (gestation >34 weeks) were screened with pulse oximetry before discharge. Infants who did not achieve predetermined oxygen saturation thresholds underwent echocardiography. All other infants were followed up to 12 months of age by use of regional and national registries and clinical follow-up. The main outcome was the sensitivity and specificity of pulse oximetry for detection of critical congenital heart defects (causing death or requiring invasive intervention before 28 days) or major congenital heart disease (causing death or requiring invasive intervention within 12 months of age). FINDINGS: 20,055 newborn babies were screened and 53 had major congenital heart disease (24 critical), a prevalence of 2·6 per 1000 livebirths. Analyses were done on all babies for whom a pulse oximetry reading was obtained. Sensitivity of pulse oximetry was 75·00% (95% CI 53·29-90·23) for critical cases and 49·06% (35·06-63·16) for all major congenital heart defects. In 35 cases, congenital heart defects were already suspected after antenatal ultrasonography, and exclusion of these reduced the sensitivity to 58·33% (27·67-84·83) for critical cases and 28·57% (14·64-46·30) for all cases of major congenital heart defects. False-positive results were noted for 169 (0·8%) babies (specificity 99·16%, 99·02-99·28), of which six cases were significant, but not major, congenital heart defects, and 40 were other illnesses that required urgent medical intervention. INTERPRETATION: Pulse oximetry is a safe, feasible test that adds value to existing screening. It identifies cases of critical congenital heart defects that go undetected with antenatal ultrasonography. The early detection of other diseases is an additional advantage. FUNDING: National Institute for Health Research Health Technology Assessment programme.

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.

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.