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.

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.

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

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

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.

Breastfeeding promotes early neonatal regulatory T-cell expansion and immune tolerance of non-inherited maternal antigens.

BACKGROUND: Breastfeeding is associated with long-term health benefits, such as a lower incidence of childhood infections, asthma, obesity and autoimmune disorders. However, little is known regarding how the maternal and neonatal immune systems interact after parturition when the neonate receives nutrition from maternal breast milk. METHODS: We undertook a comparative analysis of immune repertoire and function at birth and 3 weeks of age in a cohort of 38 term neonates born by caesarean section grouped according to feeding method (breast milk versus formula). We used flow cytometry to study the immune phenotype in neonatal and maternal blood samples and mixed lymphocyte reactions to establish the proliferation response of neonatal versus maternal lymphocytes and vice versa. The microbiome of neonatal stool samples was also investigated using 16S rRNA sequencing. RESULTS: We show that the proportion of regulatory T cells (Tregs) increases in this period and is nearly twofold higher in exclusively breastfed neonates compared with those who received formula milk only. Moreover, breastfed neonates show a specific and Treg-dependent reduction in proliferative T-cell responses to non-inherited maternal antigens (NIMA), associated with a reduction in inflammatory cytokine production. We also observed the enrichment of short chain fatty acid producing taxa (Veillonella and Gemella) in stool samples of exclusively breastfed neonates. CONCLUSIONS: These data indicate that exposure of the neonate to maternal cells through breastfeeding acts to drive the maturation of Tregs and 'tolerizes' the neonate towards NIMA.

Progesterone to prevent miscarriage in women with early pregnancy bleeding: the PRISM RCT.

BACKGROUND: Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage. OBJECTIVES: (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding. DESIGN: A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding. SETTING: A total of 48 hospitals in the UK. PARTICIPANTS: Women aged 16-39 years with early pregnancy bleeding. INTERVENTIONS: Women aged 16-39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation. MAIN OUTCOME MEASURES: The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective. RESULTS: A total of 4153 women from 48 hospitals in the UK received either progesterone (n = 2079) or placebo (n = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p = 0.08). A significant subgroup effect (interaction test p = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p = 0.004). A significant post hoc subgroup effect (interaction test p = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval -£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation. CONCLUSIONS: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 33. See the NIHR Journals Library website for further project information.

Miscarriage is a common complication of pregnancy that affects one in five pregnancies. Several small studies have suggested that progesterone, a hormone essential for maintaining a pregnancy, may reduce the risk of miscarriage in women presenting with early pregnancy bleeding. This research was undertaken to test whether or not progesterone given to pregnant women with early pregnancy bleeding would increase the number of live births when compared with placebo (dummy treatment). The women participating in the study had an equal chance of receiving progesterone or placebo, as determined by a computer; one group received progesterone (400 mg twice daily as vaginal pessaries) and the other group received placebo with an identical appearance. Treatment began when women presented with vaginal bleeding, were < 12 weeks of gestation and were found to have at least a pregnancy sac on an ultrasound scan. Treatment was stopped at 16 weeks of gestation, or earlier if the pregnancy ended before 16 weeks. Neither the participants nor their health-care professionals knew which treatment was being received. In total, 23,775 women were screened and 4153 women were randomised to receive either progesterone or placebo pessaries. Altogether, 2972 participants had a live birth after at least 34 weeks of gestation. Overall, the live birth rate in the progesterone group was 75% (1513 out of 2025 participants), compared with 72% (1459 out of 2013 participants) in the placebo group. Although the live birth rate was 3% higher in the progesterone group than in the placebo group, there was statistical uncertainty about this finding. However, it was observed that women with a history of one or more previous miscarriages and vaginal bleeding in their current pregnancy may benefit from progesterone. For women with no previous miscarriages, our analysis showed that the live birth rate was 74% (824 out of 1111 participants) in the progesterone group compared with 75% (840 out of 1127 participants) in the placebo group. For women with one or more previous miscarriages, the live birth rate was 75% (689 out of 914 participants) in the progesterone group compared with 70% (619 out of 886 participants) in the placebo group. The potential benefit appeared to be most strong for women with three or more previous miscarriages, who had a live birth rate of 72% (98 out of 137 participants) in the progesterone group compared with 57% (85 out of 148 participants) in the placebo group. Treatment with progesterone did not appear to have any negative effects.

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.

Quality of investigations into unexpected deaths of infants and young children in England after implementation of national child death review procedures in 2008: a retrospective assessment.

OBJECTIVES: In 2008, new statutory national procedures for responding to unexpected child deaths were introduced throughout England. There has, to date, been no national audit of these procedures. STUDY DESIGN: Families bereaved by the unexpected death of a child under 4 years of age since 2008 were invited to participate. Factors contributing to the death and investigations after the death were explored. Telephone interviews were conducted, and coroners' documents were obtained. The nature and quality of investigations was compared with the required procedures; information on each case was reviewed by a multiagency panel; and the death was categorised using the Avon clinicopathological classification. RESULTS: Data were obtained from 91 bereaved families (64 infant deaths and 27 children aged 1-3 years); 85 remained unexplained after postmortem examination. Documentation of multiagency assessments was poorly recorded. Most (88%) families received a home visit from the police, but few (37%) received joint visits by police and healthcare professionals. Postmortem examinations closely followed national guidance; 94% involved paediatric pathologists; 61% of families had a final meeting with a paediatrician to explain the investigation outcome. There was no improvement in frequency of home visits by health professionals or final meetings with paediatricians between 2008-2013 and 2014-2017 and no improvement in parental satisfaction with the process. CONCLUSIONS: Statutory procedures need to be followed more closely. The implementation of a national child mortality database from 2019 will allow continuing audit of the quality of investigations after unexpected child deaths. An important area amenable to improvement is increased involvement by paediatricians.