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OBJECTIVE: To validate a hypoxic ischaemic encephalopathy (HIE) prediction algorithm to identify infants at risk of HIE immediately after birth using readily available clinical data. DESIGN: Secondary review of electronic health record data of term deliveries from January 2017 to December 2021. SETTING: A tertiary maternity hospital. PATIENTS: Infants >36 weeks' gestation with the following clinical variables available: Apgar Score at 1 min and 5 min, postnatal pH, base deficit, and lactate values taken within 1 hour of birth INTERVENTIONS: Previously trained open-source logistic regression and random forest (RF) prediction algorithms were used to calculate a probability index (PI) for each infant for the occurrence of HIE. MAIN OUTCOME: Validation of a machine learning algorithm to identify infants at risk of HIE in the immediate postnatal period. RESULTS: 1081 had a complete data set available within 1 hour of birth: 76 (6.95%) with HIE and 1005 non-HIE. Of the 76 infants with HIE, 37 were classified as mild, 29 moderate and 10 severe. The best overall accuracy was seen with the RF model. Median (IQR) PI in the HIE group was 0.70 (0.53-0.86) vs 0.05 (0.02-0.15), (p<0.001) in the non-HIE group. The area under the receiver operating characteristics curve for prediction of HIE=0.926 (0.893-0.959, p<0.001). Using a PI cut-off to optimise sensitivity of 0.30, 936 of the 1081 (86.5%) infants were correctly classified. CONCLUSION: In a large unseen data set an open-source algorithm could identify infants at risk of HIE in the immediate postnatal period. This may aid focused clinical examination, transfer to tertiary care (if necessary) and timely intervention.
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BACKGROUND: T-piece is recommended for respiratory support during neonatal stabilisation. Bench studies have shown a delay >30 s in achieving changes in fraction of inspired oxygen (FiO2) at the airway when using the T-piece. Using a face mask adds dead space (DS) to the patient airway. We hypothesised that adding face mask to T-piece systems adversely affects the time required for a change in FiO2 to reach the patient. METHODS: Neopuff (Fisher and Paykel, Auckland, New Zealand) and rPAP (Inspiration Healthcare, Croydon, UK) were used to ventilate a test lung. DS equivalent to neonatal face masks was added between the T-piece and test lung. Additionally, rPAP was tested with nasal prongs. Time course for change in FiO2 to be achieved at the airway was measured for increase (0.3-0.6) and decrease (1.0-0.5) in FiO2. Primary outcome was time to reach FiO2+/-0.05 of the set target. One-way analysis of variance was used to compare mean time to reach the primary outcome between different DS volumes. RESULTS: In all experiments, the mean time to reach the primary outcome was significantly shorter for rPAP with prongs compared with Neopuff and rPAP with face mask DS (p<0.001). The largest observed difference occurred when testing a decrease in FiO2 with 10 mL tidal volume (TV) without leakage (18.3 s for rPAP with prongs vs 153.4 s for Neopuff with face mask DS). The shortest observed time was 13.3 s when increasing FiO2 with 10 mL TV with prongs with leakage and the longest time was 172.7 s when decreasing FiO2 with 4 mL TV and added face mask DS without leak. CONCLUSION: There was a delay in achieving changes in oxygen delivery at the airway during simulated ventilation attributable to the mask volume. This delay was greatly reduced when using nasal prongs as an interface. This should be examined in clinical trials.
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RATIONALE: Preterm neonates needing rescue treatments with inotropes and/or inhaled nitric oxide (iNO) (acute critical illnesses, ACIs) in neonatal intensive care units (NICUs) are at high risk of mortality. While targeted neonatal echocardiography consultations (TNE) are increasingly used to guide management, its clinical impact need evaluation. OBJECTIVES: To investigate clinical outcomes in relation to TNE utilisation during episodes of ACIs among preterm neonates. METHODS: This retrospective cohort study, conducted at two tertiary NICUs over 10 years, included neonates<37 weeks gestational age (GA) who developed ACIs. Patients receiving TNE-guided care (TNE within 24 hours of treatment initiation) were compared with non-TNE management. Outcomes included predischarge mortality, episode-related mortality (<7 days) and a new diagnosis of intraventricular haemorrhage≥grade 3 (IVH-3). Inverse probability of treatment weighting (IPTW) using propensity score was used to account for confounders, including site, birth years and baseline illness severity. MEASUREMENTS AND MAIN RESULTS: Of 622 included patients, 297 (48%) had TNE; median (IQR) GA at ACI was 26.4 (25.0-28.4) weeks. TNE group demonstrated higher baseline mean airway pressure, oxygen requirement and heart rate and frequently received both inotrope and iNO during ACI. IPTW analysis revealed TNE was associated with lower mortality (adjusted OR (95% CI) 0.75 (0.59 to 0.95)), episode-related mortality (0.54 (0.40 to 0.72)) and death or IVH-3 (0.78 (0.62 to 0.99)). TNE group received more varied inotropic agents, demonstrated earlier improvements in blood pressures, without increasing overall inotrpoic burden. CONCLUSIONS: Among preterm neonates requiring rescue treatments with inotropes/iNO, TNE utilisation to guide clinical management may be associated with improved survival.
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AIMS: To describe the prevalence of use of breastmilk and explore demographic characteristics and clinical outcomes associated with breastmilk provision in infants born <29 weeks' gestational age in Australia, New Zealand and Singapore. METHODS: This is a secondary analysis of data from a randomised controlled trial, which enrolled 1273 infants in 13 neonatal units across Australia, New Zealand and Singapore from 2012 to 2015. Infants were classified as formula-fed, donor milk-fed or mother's milk-fed at their first enteral feed and separately, at hospital discharge. RESULTS: The percentage of infants receiving mother's own milk differed between centres both at first feed (79% to 100%), and at hospital discharge (47.1% to 71.6%). Aboriginal, Torres Strait Islander and Southeast Asian heritage, drug use and smoking were associated with lower rates of fully breastmilk feeding at hospital discharge. There was no significant difference in growth outcomes, length of stay and feeding tolerance between feeding groups. CONCLUSIONS: Achieving high breastmilk feeding rates at hospital discharge for all preterm infants born <29 weeks' gestational age at hospital discharge is possible; however, targeted support for mothers who are Indigenous, Southeast Asian and/or using recreational drugs and/or smoking and/or experiencing social disadvantage may be needed. A better understanding and shared knowledge of practice variations within neonatal units with high breastfeeding rates could improve breastmilk access and equity for preterm infants. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12612000503820.
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OBJECTIVE: To investigate the perspectives of experienced parents regarding guidelines and personalisation for managing imminent extremely premature births (22-26 weeks gestational age (GA)) . The study examined four scenarios: no guideline, a guideline based on GA, a guideline based on GA plus other factors and a guideline based on a calculated prognosis. DESIGN: Nineteen semistructured qualitative interviews were conducted with Dutch parents who experienced (imminent) extremely premature births between 23+5 and 26+2 weeks of gestation. Diversity was aimed for through purposive sampling from a database created prior to this study. Four of the parents opted for palliative care. Among the parents who chose intensive care, in nine cases the infant(s) survived. RESULTS: All participants acknowledged the necessity of having a periviability guideline because it would provide valuable decision-making support, and counterbalance decisions solely based on parental instincts to save their infant. Parents preferred guidelines that considered multiple prognostic factors beyond GA alone, without overwhelming parents with information, because more information would not necessarily make the decision easier for parents. Personalisation was defined by parents mainly as 'being seen and heard' and associated with building relationships with healthcare professionals and effective communication between them and professionals. CONCLUSIONS: The results underscore the importance of having a periviability guideline including multiple prognostic factors to assist parents in making decisions at the limit of viability, and the importance of a personalised care approach to meet parental needs in the context of imminent extremely preterm birth.
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OBJECTIVE: When extremely premature birth at the limits of viability is imminent, shared decision-making with parents regarding the infant's treatment is widely recommended. Aligning decisions with parental values can be challenging. So, this study aims to get insight into (1) what values parents considered important in their decision, (2) whether their decision was based on intuition and/or rational analysis and (3) parental suggestions on how to help explore and articulate values during prenatal counselling. DESIGN: A qualitative study was performed among Dutch parents who experienced (imminent) extremely premature birth. Diversity was aimed for through purposive sampling. Semistructured interviews were conducted until saturation was achieved. Transcripts were coded and themes were derived from the data. RESULTS: Nineteen interviews were performed. Results show what parents considered important in their decision, such as the infants' future, family life and 'giving a chance'. Most parents made their decision more intuitively rather than rationally, for others both coexisted. Particularly fathers and parents who opted for palliative comfort care experienced the decision as rational. Parents would have liked to explore values, but found it challenging. They suggested strategies and conditions to help explore and articulate their values during counselling, such as a multidisciplinary approach. CONCLUSIONS: Various considerations and underlying values were found to be important. Parents recognise the influence of emotions and intuition in decision-making and struggle to articulate their values, emphasising the need for guidance. Healthcare providers should engage in open, personalised discussions to facilitate value exploration, enabling informed decisions aligned with parental values.
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BACKGROUND: Heat-inactivated probiotics (HPs) may provide an effective alternative to live probiotics (P) by avoiding their risks (eg, probiotic sepsis) while retaining the benefits. We assessed the safety and efficacy of a HP in very preterm (VP: gestation <32 weeks) infants. METHODS: VP infants were randomly allocated to receive a HP or P mixture (Bifidobacterium breve M-16V, Bifidobacterium longum subsp. infantis M-63, Bifidobacterium longum subsp. longum BB536, total 3×109 CFU/day) assuring blinding. Primary outcome was faecal calprotectin (FCP) levels were compared after 3 weeks of supplementation. Secondary outcomes included faecal microbiota and short chain fatty acid (SCFA) levels. RESULTS: 86 VP infants were randomised to HP or P group (n=43 each). Total FCP and SCFA were comparable between HP and P groups within 7 days (T1) and between day 21 and 28 (T2) after supplementation. At T2, median (range) FCP was 75 (8-563) in the HP group and 80 (21-277) in the P group (p=0.71). Propionate was significantly raised in both groups, while butyrate was significantly raised in the HP group (all p<0.01). Bacterial richness and diversity increased but was comparable between HP and P (p>0.05). Beta diversity showed similar community structures in both groups (all p>0.05). Changes in faecal Actinobacteria, Bacteroidetes and Bifidobacteriacae levels were comparable in both groups at T1 and T2. There was no probiotic sepsis. CONCLUSIONS: HP was safe and showed no significant difference in FCP as compared with a live probiotic. Adequately powered trials are needed to assess the effects of HP on clinically significant outcomes in preterm infants. TRIAL REGISTRATION NUMBER: ACTRN12618000489291.
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OBJECTIVES: Little is known about decision regret following extremely premature birth. We assessed decision regret in women who delivered an extremely premature infant, comparing decision regret scores based on resuscitation decision. METHODS: Electronic survey assessment of decision regret using a validated tool included women who delivered at 22-25 completed weeks of gestation at two hospitals 2004-2019. Comparison of 'active care', 'comfort care' and 'other' groups was quantified and comments reviewed. RESULTS: 442 of 787 (56%) eligible women were contacted, 242 of 442 (55%) completed surveys, response rate 242 of 787 (31%). Women not contacted were younger (p=0.0001) and/or delivered in an earlier year (p=0.002). There was a higher percentage of white women who completed the survey (p=0.004). Decision regret was elevated in all groups, varied widely, but was lower in 'active care' compared with 'comfort care' (Decision Regret Score 14 vs 39, p<0.0001). Lower decision regret occurred in women who recalled a prenatal consult (p=0.014) or identified as the primary decision-maker compared with women who perceived the doctor had a major role (p=0.02) or made the decision (p<0.0001). Lower decision regret occurred in women whose infant was alive at survey completion compared with women whose infant died in the hospital (p<0.0001) or after discharge (p=0.01). CONCLUSIONS: Decision regret was elevated in all groups. Women who recalled prenatal consultation, identified as the primary decision-maker, chose intensive care and/or whose infant survived had lower regret scores. CLINICAL TRIAL REGISTRATION: NCT04074525.
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OBJECTIVE: To determine the accuracy of pre-extubation lung ultrasound (LUS) to predict reintubation in preterm infants born <32 weeks' gestation. DESIGN: Prospective diagnostic accuracy study. SETTING: Two neonatal intensive care units. METHODS: Anterior and lateral LUS was performed pre-extubation. The primary outcome was the accuracy of LUS scores (range 0-24) to predict reintubation within 72 hours. Secondary outcomes were accuracy in predicting (1) reintubation within 7 days, (2) reintubation stratified by postnatal age and (3) accuracy of lateral imaging only (range 0-12). Pre-specified subgroup analyses were performed in extremely preterm infants born <28 weeks' gestation. Cut-off scores, sensitivities and specificities were calculated using receiver operating characteristic analysis and reported as area under the curves (AUCs). RESULTS: One hundred preterm infants with a mean (SD) gestational age of 27.4 (2.2) weeks and birth weight of 1059 (354) g were studied. Thirteen were subsequently reintubated. The AUC (95% CI) of the pre-extubation LUS score for predicting reintubation was 0.63 (0.45-0.80). Accuracy was greater in extremely preterm infants: AUC 0.70 (0.52-0.87) and excellent in infants who were <72 hours of age at the time of extubation: AUC 0.90 (0.77-1.00). Accuracy was poor in infants who were >7 days of age. Lateral imaging alone demonstrated similar accuracy to scanning anterior and lateral regions. CONCLUSIONS: In contrast to previous studies, LUS was not a strong predictor of reintubation in preterm infants. Accuracy is increased in extremely preterm infants. Future research should focus on infants at highest risk of extubation failure and consider simpler imaging protocols. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry: ACTRN12621001356853.
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OBJECTIVE: To investigate in extremely low birthweight (ELBW; <1000 g) babies the associations between refeeding syndrome (serum phosphate <1.4 mmol·L-1 and serum total calcium>2.8 mmol·L-1) and hypophosphataemia in the first week and death or neurodisability at 2 years' corrected age (CA). DESIGN: Secondary cohort analysis of the ProVIDe trial participants with serum biochemistry within 7 days of birth. At 2 years' CA, neurodisability was assessed by Bayley Scales of Infant Development Edition III and neurological examination. Associations between neurodisability and other variables were analysed using t-tests and logistic regression adjusted for sex and smallness-for-gestational age. SETTING: Six tertiary neonatal intensive care units (NICUs) in New Zealand. PARTICIPANTS: 352 ELBW babies born between 29 April 2014 and 30 October 2018. MAIN OUTCOME MEASURE: Death or neurodisability at 2 years' CA. RESULTS: Fifty-nine babies died, two after discharge from the NICU. Of the 336 babies who survived to 2 years' CA, 277 had neurodevelopmental assessment and 107 (39%) had a neurodisability. Death or neurodisability was more likely in babies who had refeeding syndrome (aOR 1.96 (95% CI 1.09 to 3.53), p=0.02) and in babies who had hypophosphataemia (aOR 1.74 (95% CI 1.09 to 2.79), p=0.02). Hypophosphataemia was associated with increased risk of death (aOR 2.07 (95% CI 1.09 to 3.95), p=0.03)) and severe hypophosphataemia (<0.9 mmol·L-1) with increased risk of death (aOR 2.67 (95% CI 1.41 to 5.00), p=0.002) and neurodisability (aOR 2.31 (95% CI 1.22 to 4.35), p=0.01). CONCLUSIONS: In ELBW babies, refeeding syndrome and hypophosphataemia in the first week are associated with death or neurodisability. Until optimal phosphate requirements are determined through further research, monitoring for hypophosphataemia and mitigation strategies are indicated. TRIAL REGISTRATION NUMBER: ACTRN12612001084875.
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OBJECTIVE: To assess trends in antibiotic use across a large cohort of extremely low birth-weight (<1000 g; ELBW) infants admitted to academic and community neonatal intensive care units (NICUs) across the USA over a 13-year period. DESIGN: Repeated cross-sectional cohort study. SETTING: Premier Health Database, a comprehensive administrative database of inpatient encounters from academic and community hospitals across the US. PATIENTS: ELBW inborn infants admitted to NICUs from 1 January 2009 to 31 December 2021. INTERVENTIONS: N/A MAIN OUTCOME MEASURES: Absolute and relative changes in (1) proportion of ELBW infants with antibiotic exposure and (2) days of therapy (DOT) per 1000 patient days, over time. Average annual differences were estimated using generalised linear regression with 95% CI. Disposition trends were also measured. RESULTS: Among 36 701 infants admitted to 402 NICUs, the proportion exposed to antibiotics was essentially unchanged (89.9% in 2009 to 89.3% in 2021; absolute reduction of -0.6%); generalised linear regression estimated an annual absolute difference of -0.3% (95% CI (-0.6%) to (-0.07%); p=0.01). DOT per 1000 patient days decreased from 337 in 2009 to 210 in 2021, a 37.8% relative difference and annual relative difference of -4.3% ((-5.2%) to (-3.5%); p<0.001). Mortality was unchanged during the study period. CONCLUSIONS: We found a substantial reduction in antibiotic DOT despite no substantive change in the proportion of infants exposed to antibiotics. This suggests the success of stewardship efforts aimed at antibiotic duration and highlight the need for improved approaches to identifying ELBW infants at highest risk of infection.
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OBJECTIVE: To describe the incidence of major bleeds according to different platelet counts in very preterm infants, and to explore whether this association is influenced by other risk factors for bleeding. DESIGN: Observational cohort study. SETTING: A Dutch tertiary care neonatal intensive care unit. PATIENTS: All consecutive infants with a gestational age at birth <32 weeks admitted between January 2004 and July 2022. EXPOSURE: Infants were stratified into nine groups based on their nadir platelet count (×109/L) during admission (<10, 10-24, 25-49, 50-99, 100-149, 150-199, 200-249, 250-299 and ≥300), measured before the diagnosis of a major bleed and before any platelet transfusion was administered. MAIN OUTCOME MEASURE: Incidence of major bleeds during admission. Logistic regression analysis was used to quantify the relationship between nadir platelet count and incidence of major bleeds. RESULTS: Among 2772 included infants, 224 (8%) developed a major bleed. Of the infants with a major bleed, 92% (206/224) had a nadir platelet count ≥50×109/L. The incidence of major bleeds was 8% among infants with and without severe thrombocytopenia (platelet count <50×109/L), 18/231 (95% CI 5 to 12) and 206/2541 (95% CI 7 to 9), respectively. Similarly, after adjustment for measured confounders, there was no notable association between nadir platelet counts below versus above 50×109/L and the occurrence of major bleeds (OR 1.09, 95% CI 0.61 to 1.94). CONCLUSION: In very preterm infants, the vast majority of major bleeds occur in infants without severe thrombocytopenia.