Neonatal Docosahexaenoic Acid in Preterm Infants and Intelligence at 5 Years.

BACKGROUND: Docosahexaenoic acid (DHA) is a component of neural tissue. Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before 29 weeks' gestation do not receive the normal supply of DHA. The effect of this deficiency on subsequent cognitive development is not well understood. METHODS: We assessed general intelligence at 5 years in children who had been enrolled in a trial of neonatal DHA supplementation to prevent bronchopulmonary dysplasia. In the previous trial, infants born before 29 weeks' gestation had been randomly assigned in a 1:1 ratio to receive an enteral emulsion that provided 60 mg of DHA per kilogram of body weight per day or a control emulsion from the first 3 days of enteral feeds until 36 weeks of postmenstrual age or discharge home, whichever occurred first. Children from 5 of the 13 centers in the original trial were invited to undergo assessment with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 5 years of corrected age. The primary outcome was the full-scale intelligence quotient (FSIQ) score. Secondary outcomes included the components of WPPSI. RESULTS: A total of 1273 infants underwent randomization in the original trial; of the 656 surviving children who had undergone randomization at the centers included in this follow-up study, 480 (73%) had an FSIQ score available - 241 in the DHA group and 239 in the control group. After imputation of missing data, the mean (±SD) FSIQ scores were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group (adjusted difference, 3.45; 95% confidence interval, 0.38 to 6.53; P = 0.03). The results for secondary outcomes generally did not support that obtained for the primary outcome. Adverse events were similar in the two groups. CONCLUSIONS: In infants born before 29 weeks' gestation who had been enrolled in a trial to assess the effect of DHA supplementation on bronchopulmonary dysplasia, the use of an enteral DHA emulsion until 36 weeks of postmenstrual age was associated with modestly higher FSIQ scores at 5 years of age than control feeding. (Funded by the Australian National Health and Medical Research Council and Nu-Mega Ingredients; N3RO Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.).

Early mortality among aboriginal and non-aboriginal women who had a preterm birth in Western Australia: A population-based cohort study.

BACKGROUND: Having a preterm (<37 weeks' gestation) birth may increase a woman's risk of early mortality. Aboriginal and Torres Strait Islander (hereafter Aboriginal) women have higher preterm birth and mortality rates compared with other Australian women. OBJECTIVES: We investigated whether a history of having a preterm birth was associated with early mortality in women and whether these associations differed by Aboriginal status. METHODS: This retrospective cohort study used population-based perinatal records of women who had a singleton birth between 1980 and 2015 in Western Australia linked to Death Registry data until June 2018. The primary and secondary outcomes were all-cause and cause-specific mortality respectively. After stratification by Aboriginal status, rate differences were calculated, and Cox proportional hazard regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cause-specific mortality. RESULTS: There were 20,244 Aboriginal mothers (1349 deaths) and 457,357 non-Aboriginal mothers (7646 deaths) with 8.6 million person-years of follow-up. The all-cause mortality rates for Aboriginal mothers who had preterm births and term births were 529.5 and 344.0 (rate difference 185.5, 95% CI 135.5, 238.5) per 100,000 person-years respectively. Among non-Aboriginal mothers, the corresponding figures were 125.5 and 88.6 (rate difference 37.0, 95% CI 29.4, 44.9) per 100,000 person-years. The HR for all-cause mortality for Aboriginal and non-Aboriginal mothers associated with preterm birth were 1.48 (95% CI 1.32, 1.66) and 1.35 (95% CI 1.26, 1.44), respectively, compared with term birth. Compared with mothers who had term births, mothers of preterm births had higher relative risks of mortality from diabetes, cardiovascular, digestive and external causes. CONCLUSIONS: Both Aboriginal and non-Aboriginal women who had a preterm birth had a moderately increased risk of mortality up to 38 years after the birth, reinforcing the importance of primary prevention and ongoing screening.

Survey of clinical staff knowledge on the long-term outcomes of very preterm infants delivered in a tertiary referral hospital.

AIM: To assess knowledge of our neonatal intensive care unit clinical staff regarding preterm neurodevelopmental outcomes using the 33-item Preterm Birth Knowledge Scale (PB-KS). METHODS: An anonymous convenience sampling survey of clinical staff in the Neonatal Directorate was conducted between July and December 2019. PB-KS, demographic information and prior staff education on long-term outcomes in very preterm infants were collected. RESULTS: There were 56 responses (five neonatologists, eight paediatric trainees, 41 neonatal nurses and two allied health staff). Responses were scored as correct or incorrect. The mean score on the PB-KS was 19.5 (range: 4-29 out of 40) with 50% correct answers. Accuracy was highest (96%) for rates of cerebral palsy and lowest (11%) for estimation of quality of life among preterm survivors. Staff reported training in long-term outcomes of preterm infants through attending a conference/seminar (20%) or a combination of formal training and seminars (41.1%). Over half of our clinical staff reported a lack of formal training. Formally trained clinical staff scored significantly better in this survey. Didactic seminars were indicated as preferred choice for staff education. CONCLUSIONS: Results of our survey will assist in developing a customised educational programme to address identified gaps in the knowledge of clinical staff as our survey also showed significantly better scores among staff who were formally trained about long-term outcomes in very preterm infants. Staff responses indicated that knowledge on long-term outcomes was variable but more accurate with regard to more severe disabilities and shorter-term developmental outcomes.

Observational study using video recordings to explore the first hour after admission to a neonatal intensive care unit.

AIM: To explore the admission process to our neonatal intensive care unit. METHODS: A first phase quality improvement initiative was conducted. We utilised observational video recording of a convenience sample of inborn admissions. Two remote GoPro cameras were placed, one giving an overview of activity and the other focussed on the infant. Recordings captured the first hour after admission including transfer to the neonatal intensive care unit by the birthing team. The video footage of each case study was reviewed by a multidisciplinary panel using an agreed semi-quantitative analysis of events. RESULTS: Ten admissions to the neonatal intensive care unit were video recorded between June and October 2018. Gestational age 282 -401 . A focus on maintaining airway support was inconsistent as was the ability to provide continuous monitoring of vital signs. Overall leadership of the process was lacking and handover often appeared fragmented. Median temperature on admission was 362 (354 -373 ) °C. Vascular access and fluid management occurred at a median of 36 (13-67) minutes. CONCLUSIONS: Planning and approval for this study were protracted, particularly negotiating the use of video recording. Anecdotally, this delay is thought to have contributed to an improvement in managing admissions, particularly when maintaining airway support and monitoring. However, our baseline data have highlighted a lack of leadership, fragmented handover, low admission temperatures and broad time frames to achieve vascular access. A guideline to streamline handover and nursery transition is currently being implemented; a subsequent evaluation cycle is planned.

When can I hold my baby? An audit of time to first cuddle for preterm babies (<32 weeks) pre introduction and post introduction of a Family-Integrated Care model.

AIM: The audit examined time to first cuddle between preterm babies (born < 32 weeks) and their parent pre- and post-introduction of a family-integrated care model. Secondary outcomes included time to full feeds and length of neonatal intensive care stay. BACKGROUND: Parental separation due to neonatal intensive care unit admission is known to negatively affect parental and baby wellbeing. DESIGN: A "before-after" design compared outcomes for babies admitted pre- (2015) and post (2018)-implementation of the model in a Western Australian neonatal intensive care unit. METHODS: A retrospective medical record audit included babies from two gestational age groups in 2015 and 2018, born ≤27 + 6 weeks and 28-31 + 6 weeks. SQUIRE checklist guided reporting of the audit. RESULTS: One hundred fifty-three babies were included in the audit, 79 from 2015 (≤27 + 6 weeks n = 39 and 28-31 + 6 weeks n = 40) and 74 from 2018 (≤27 + 6 weeks n = 35 and 28-31 + 6 weeks n = 39). Babies in both years were born at similar median gestational ages with comparable birthweights. Babies born ≤27 + 6 weeks in 2018 were cuddled earlier (median = 141 h old) compared with those in 2015 (median = 157 h old). Median time to reach full feeds decreased and was significant in the ≤27 + 6-week group: 288 h (12 days) in 2015 to 207.5 h (8.6 days) in 2018. Length of stay was longer for the ≤27 + 6-week gestation 2018 group (median = 64 days) and 28-31 + 6-week gestation 2018 group (median = 22 days). CONCLUSION: Family-integrated care models may decrease the time to first cuddle and full feeds. Further research on outcomes such as breastfeeding, infant weight gain and length of stay can extend existing knowledge. RELEVANCE TO CLINICAL PRACTICE: Family-integrated care models may offer benefits to families of hospitalised preterm babies and investigating barriers to its implementation and creation of solutions to overcome barriers warrants attention.

Reporting the incidence of unplanned extubation in the neonatal intensive care unit.

AIM: The aim of this study was to highlight the incidence of unplanned extubation (UE) and identify associated factors in our neonatal population. METHODS: This study was a prospective audit. RESULTS: A specifically designed audit tool was used to capture UE events; 182 neonates required mechanical ventilation for 863 days. There were 41 episodes of UE. The UE rate was 4.75 per 100 days of ventilation. At the time of UE, median gestational age of patients was 27.3 weeks (23.4-37.6), with a corrected age median of 29.2 weeks (23.4-37.6). Re-intubation was required in two thirds of the patients for increasing apnoea and increased work of breathing. Endotracheal tubes are secured in a standardised way either using Neobar or brown tape. UE events occurred with both methods. The two most common factors associated with UE included active handling of the baby and the time of day (0700-1000 h). CONCLUSIONS: This audit has provided our neonatal intensive care unit with a benchmark for improvement. It has also created staff awareness of the risk of UE and promoted staff engagement to reduce UE. A bundle approach to reduce UE has been introduced. Future audits are planned to monitor the impact of these initiatives.

Survival and neurodevelopmental outcomes in extremely preterm infants 22-24 weeks of gestation born in Western Australia.

AIM: The management of births at borderline viability continues to present dilemmas for health professionals and parents. The aim of the study was to review local outcomes of infants born between 22 and 24 weeks of gestation between 2004 and 2010 in Western Australia (WA) to aid perinatal counselling. METHODS: Survival data for the study were sourced retrospectively from the Neonatal Clinical Care Unit and Department of Health records of births in WA. Neurodevelopmental follow-up outcomes were assessed using the most recent standardised assessment (Griffiths, Bayley-III and Wechsler Preschool and Primary Scale of Intelligence, 3rd Ed) and medical examination of infants/children 12 months to 8 years from follow-up clinic appointments. RESULTS: At these gestations, 159 survivors represented 72% of neonatal intensive care unit admissions, 53% of WA live births and 26% of WA live and still births; 5% of live births survived at 22 weeks, 46% at 23 weeks and 77% at 24 weeks. Of the 14 outborn/retrieved infants, 4 survived (29%). At a median age of 59 months, disabilities were severe in 13% of children (22-23w = 19%; 24w = 11%). The median test quotient was 90. Moderate and severe cognitive disability was found in 16%, cerebral palsy was found in 7% (n = 11), and 55% of children were free from impairment as defined in this study. CONCLUSION: At these gestations, survival figures varied markedly with the chosen population denominator. Regional data are essential for valid population comparison. While many developmental difficulties occurred in these children, 78% were free from moderate or severe impairment at ages 3-5 years.

Transition from hospital to home: Parents' perception of their preparation and readiness for discharge with their preterm infant.

AIMS AND OBJECTIVES: To explore the experiences of parents with babies born between 28-32 weeks' gestation during transition through the neonatal intensive care unit and discharge to home. BACKGROUND: Following birth of a preterm baby, parents undergo a momentous journey through the neonatal intensive care unit prior to their arrival home. The complexity of the journey varies on the degree of prematurity and problems faced by each baby. The neonatal intensive care unit environment has many stressors and facilitating education to assist parents to feel ready for discharge can be challenging for all health professionals. DESIGN: Qualitative descriptive design. METHODS: The project included two phases, pre- and postdischarge, to capture the experiences of 20 couples (40 parents), whilst their baby was a neonatal intensive care unit inpatient and then after discharge. Face-to-face interviews, an online survey and telephone interviews were employed to gather parent's experiences. Constant comparative analysis was used to identify commonalities between experiences. Recruitment and data collection occurred from October 2014-February 2015. RESULTS/FINDINGS: Overlapping themes from both phases revealed three overarching concepts: effective parent staff communication; feeling informed and involved; and being prepared to go home. CONCLUSION: Our findings can be used to develop strategies to improve the neonatal intensive care unit stay and discharge experience for parents. Proposed strategies would be to improve information transfer, promote parental contact with the multidisciplinary team, encourage input from fathers to identify their needs and facilitate parental involvement according to individual needs within families. RELEVANCE TO CLINICAL PRACTICE: Providing information to parents during their time in hospital, in a consistent and timely manner is an essential component of their preparation when transitioning to home.

Young adult outcomes following premature birth: A Western Australian experience.

BACKGROUND: Childhood outcomes following preterm birth are widely published, however long-term adult outcomes are less well described. We aimed to determine the quality of life and burden of co-morbidities experienced by preterm-born young adults in Western Australia. METHODS: A retrospective observational study was conducted. Participants born at 23-33 weeks gestation cared for at King Edward Memorial Hospital during 1990 and 1991 were recruited from a historical birth cohort. Participants completed general, medical and reproductive health questionnaires. Results were compared with contemporaneous cohort data and/or population statistics. RESULTS: Questionnaires were received from 73 young adults aged 28 to 30 years. The majority of respondents completed high school (94.5 %), were employed fulltime (74.0 %) and had close friends and family relationships. Almost all the participants considered their health to be good (94.0 %) and participated in light exercise (90.0 %). Increased hypertension, hypercholesterolaemia, asthma, neuropsychiatric conditions and visual impairment were reported. Depression Anxiety and Stress Scale (DASS-21) scoring identified increased mild anxiety. Increased consultation with healthcare workers and use of prescription medications were reported. CONCLUSION: The group of preterm-born adults surveyed reported a good quality of life, supportive interpersonal relationships and they provided significant contributions to society. They did report increased medical and psychological conditions than the general population.

Childhood outcomes after maternal antenatal sildenafil treatment for severe early-onset fetal growth restriction: a randomized trial (STRIDER NZAus).

In this follow-up at 2.5 years of children from the STRIDER NZAus Trial (N = 112), in which women with singleton pregnancies affected by severe early fetal growth restriction were randomized to sildenafil citrate 75 mg daily or placebo until 32 weeks, there was no difference between groups in survival without neurosensory impairment, defined as any of cerebral palsy, deafness, blindness, cognitive delay (Bayley III cognition or language score >1 SD below mean) or motor delay: 30/56[54%] vs. 34/56[61%]; aOR = 0.74, 95%CI: 0.31, 1.77. However, children exposed to sildenafil appeared to be more likely to have cognitive delay (13/45[29%] vs. 4/40[10%]; aOR = 3.71, 95% CI: 1.01, 13.63) but less likely to have emotional-behavioural difficulties (2/43[5%] vs. 8/38[21%]; aOR = 0.19, 95%CI: 0.03, 1.00). Conclusion: maternal sildenafil treatment for severe early-onset FGR was not associated with altered survival free of neurosensory impairment at 2.5 years' corrected age.

High-Dose Docosahexaenoic Acid in Newborns Born at Less Than 29 Weeks' Gestation and Behavior at Age 5 Years: Follow-Up of a Randomized Clinical Trial.

Importance: Children born at less than 29 weeks' gestation are at risk of behavioral difficulties. This may be due in part to the lack of transplacental supply of docosahexaenoic acid (DHA), a key fatty acid with structural and functional roles in the brain. Objective: To determine whether meeting the neonatal DHA requirement through supplementation is associated with improved behavioral functioning of children born at less than 29 weeks' gestation. Design, Setting and Participants: This was a follow-up of children from 10 Australian participating centers in a multi-center, blinded, parallel group randomized clinical trial of infants born at less than 29 weeks' gestation conducted from June 2012 and September 2015, excluding those with additional fatty acid supplementation or major congenital or chromosomal abnormalities. Follow-up took place from August 2018 to May 2021. Parents of surviving children who had not withdrawn from the original trial were invited to complete questionnaires when the child turned 5 years' corrected age. Interventions: Infants were randomized to receive daily enteral emulsions providing 60 mg/kg/d of DHA or a soy-oil emulsion (with no DHA) from within the first 3 days of enteral feeding until 36 weeks' postmenstrual age or discharge home, whichever occurred first. Main Outcomes and Measures: The primary outcome of this follow-up was parent-rated behavior and emotional functioning as indicated by the Total Difficulties score of the Strengths and Difficulties Questionnaire. Parents also completed questionnaires about their child's behavioral manifestations of executive functioning, as well as a range of health outcomes to assess potential longer-term side effects of DHA intervention. Results: Primary outcome data were available for 731 children (76% of 958 surviving eligible children; 361 in the intervention group and 370 in the control group). Of these 731, 452 (47%) were female, and the mean (SD) corrected age at follow-up was 5.4 (0.5) years. Following imputation for missing data, the mean Total Difficulties score was the same in both groups (intervention group, n = 465; mean [SD], 11.8 [6.3]; control group, n = 493; mean [SD], 11.8 [6.0]; mean difference adjusted for sex, gestational age stratum, and hospital, 0.01; 95% CI, -0.87 to 0.89; P = .98). There was no evidence for differences between the groups in any secondary outcomes of behavior, executive functioning, or health. Conclusions and Relevance: In this follow-up of a randomized clinical trial, enteral DHA supplementation at the equivalent of the estimated in utero dose for infants born at less than 29 weeks' gestation did not improve behavioral functioning at age 5 years. There were no indications of adverse effects with DHA supplementation. Trial Registration: Australian New Zealand Clinical Trial Registry: ACTRN12612000503820.

Evaluating hypoxia during air travel in healthy infants.

Up to a third of ex-preterm infants flying near term exhibit pulse oxygen saturation (SpO2) of less than 85% during air travel. A hypoxia challenge test (HCT) is recommended to evaluate the requirement for in-flight supplemental O2. The validity of the HCT in healthy, term infants has not been reported. This study aimed to characterise the in-flight hypoxia response and the accuracy of the HCT to predict this response in healthy, term infants in the first year of life. Infants (n=24: (15 male)) underwent a HCT prior to commercial air travel during which parents monitored SpO2. Thirty-two flights were undertaken with six infants completing multiple flights. The median in-flight SpO2 nadir was 87% and significantly lower than the HCT SpO2 nadir (92%: p<0.001). Infants on seven flights recorded SpO2<85% with one infant recording a HCT with a SpO2 less than 85%. There was marked variability in the in-flight SpO2 in the six infants who undertook multiple flights, and for three of these infants, the SpO2 nadir was both above and below 85%. We report that in healthy term infants an in-flight SpO2 below 85% is common and can vary considerably between flights and that the HCT poorly predicts the risk of in-flight hypoxia (SpO2<85%). As it is common for healthy term infants to have SpO2 less than 85% during air travel further research is needed to clarify whether this is an appropriate cut-off in this age group.

Evaluation of the frequency and obstetric risk factors associated with term neonatal admissions to special care units.

INTRODUCTION: Approximately 10-15% of term babies may require admission to neonatal special care units. This level of care is frequently an unexpected event for parents. AIMS: To review the frequency and obstetric risk factors associated with the admission of term neonates to a tertiary hospital special care unit (SCN). MATERIALS AND METHODS: All babies born ≥37-weeks gestation admitted to the SCN at King Edward Memorial Hospital between 2004 and 2006 were identified from the institutional maternity and neonatal databases. Maternal and obstetric factors were reviewed to identify potential predictors of admission to the SCN. RESULTS: During the study period, 1671 term neonates born to 1624 women were admitted to the SCN (14.4% of term deliveries). Neonatal intensive care unit admissions accounted for 10.6% of the term admissions. The most common reasons for SCN admission were respiratory complications (n = 421, 25.2%), observation postresuscitation (n = 402, 24.1%) and hypoglycaemia (n = 152, 9.1%). Elective caesarean delivery was significantly associated with admission to the special care unit for respiratory complications compared with all other delivery modes (37 vs 23%, P < 0.001), particularly if the birth occurred at <39-weeks gestation (38 vs 24%, P < 0.001). CONCLUSIONS: In our population of women delivering at a tertiary maternity facility, approximately 1:8 term babies were admitted to the neonatal special care unit. Elective caesarean delivery was associated with a significant risk of admission for respiratory complications compared with other birth modes, especially when <39-weeks gestation.

Outcomes to 5 years of outborn versus inborn infants <32 weeks in Western Australia: a cohort study of infants born between 2005 and 2018.

OBJECTIVE: We compared mortality and morbidity of inborn versus outborn very preterm infants <32 weeks' gestation in Western Australia (WA) between 2005 and 2018. DESIGN: Retrospective cohort study. PATIENTS: Infants <32 weeks' gestation who were born in WA. MAIN OUTCOME MEASURES: Mortality was assessed as death before discharge home from the tertiary neonatal intensive care unit. Short-term morbidities included combined brain injury (intracranial haemorrhage grade ≥3 and cystic periventricular leukomalacia) and other major neonatal outcomes. Developmental assessments at age 2, 3 and 5 years were evaluated. We performed multivariable logistic regression analysis of outborn status on outcomes, controlling for gestational age, birth weight z-score, sex and multiple birth. RESULTS: A total of 4974 infants were born in WA between 22 and 32 weeks' gestation between 2005 and 2018 of which 4237 (89.6%) were inborn and 443 (10.4%) were outborn. Overall mortality to discharge was higher in outborn infants (20.5% (91/443) vs 7.4% (314/4237); adjusted OR (aOR) 2.44, 95% CI 1.60 to 3.70, p<0.001). Outborn infants had higher rates of combined brain injury than those inborn (10.7% (41/384) vs 6.0% (246/4115); aOR 1.98, 95% CI 1.37 to 2.86), p<0.001). No difference in up to 5-year developmental measures was detected. Follow-up data were available for 65% of outborn and 79% of inborn infants. CONCLUSIONS: Outborn preterm infants <32 weeks in WA had increased odds of mortality and combined brain injury than those inborn. Developmental outcomes up to 5 years were similar between groups. Loss to follow-up may have impacted the long-term comparison.

Mediation Analysis to Untangle Opposing Associations of High-Dose Docosahexaenoic Acid With IQ and Bronchopulmonary Dysplasia in Children Born Preterm.

Importance: High-dose omega-3 docosahexaenoic acid (DHA) supplementation of children born at less than 29 weeks' gestation has been shown to improve IQ despite increasing the risk of bronchopulmonary dysplasia (BPD). Given that BPD is associated with poorer cognitive outcomes, it is unclear whether the increased risk of BPD with DHA supplementation is associated with decreased benefit to IQ. Objective: To investigate whether the increased risk of BPD with DHA supplementation was associated with diminished IQ benefit. Design, Setting, and Participants: This cohort study used data collected from a multicenter, blinded, randomized controlled trial of DHA supplementation in children born at less than 29 weeks' gestation. Participants were recruited from 2012 to 2015 and followed up until 5 years' corrected age. Data were analyzed from November 2022 to February 2023. Interventions: Enteral DHA emulsion (60 mg/kg/d, to match the estimated in-utero requirement) or a control emulsion from the first 3 days of enteral feeds until 36 weeks' postmenstrual age or discharge home. Main Outcomes and Measures: Physiological BPD was assessed at 36 weeks' postmenstrual age. IQ was assessed at 5 years' corrected age using the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition; children from the 5 highest-recruiting Australian hospitals were assessed. The total effect of DHA supplementation on IQ was divided into direct and indirect effects using mediation analysis, with BPD as the presumed mediating variable. Results: Among 656 surviving children from hospitals involved in IQ follow-up (mean [SD] gestational age at birth, 26.8 [1.4] weeks; 346 males [52.7%]), there were 323 children with DHA supplementation and 333 children in the control group. Mean IQ was 3.45 points (95% CI, 0.38 to 6.53 points) higher in the DHA group than the control group, despite an increase in the risk of BPD (160 children [49.7%] vs 143 children [42.8%] with BPD). The indirect effect of DHA on IQ via BPD was not statistically significant (-0.17 points; 95% CI, -0.62 to 0.13 points), with most of the effect of DHA on IQ occurring independently of BPD (direct effect = 3.62 points; 95% CI, 0.55 to 6.81 points). Conclusions and Relevance: This study found that associations of DHA with BPD and IQ were largely independent. This finding suggests that if clinicians supplement children born preterm with high-dose DHA, any resulting increase in BPD risk would not be associated with meaningful reductions in the IQ benefit.

What Makes a Quality Health App-Developing a Global Research-Based Health App Quality Assessment Framework for CEN-ISO/TS 82304-2: Delphi Study.

BACKGROUND: The lack of an international standard for assessing and communicating health app quality and the lack of consensus about what makes a high-quality health app negatively affect the uptake of such apps. At the request of the European Commission, the international Standard Development Organizations (SDOs), European Committee for Standardization, International Organization for Standardization, and International Electrotechnical Commission have joined forces to develop a technical specification (TS) for assessing the quality and reliability of health and wellness apps. OBJECTIVE: This study aimed to create a useful, globally applicable, trustworthy, and usable framework to assess health app quality. METHODS: A 2-round Delphi technique with 83 experts from 6 continents (predominantly Europe) participating in one (n=42, 51%) or both (n=41, 49%) rounds was used to achieve consensus on a framework for assessing health app quality. Aims included identifying the maximum 100 requirement questions for the uptake of apps that do or do not qualify as medical devices. The draft assessment framework was built on 26 existing frameworks, the principles of stringent legislation, and input from 20 core experts. A follow-up survey with 28 respondents informed a scoring mechanism for the questions. After subsequent alignment with related standards, the quality assessment framework was tested and fine-tuned with manufacturers of 11 COVID-19 symptom apps. National mirror committees from the 52 countries that participated in the SDO technical committees were invited to comment on 4 working drafts and subsequently vote on the TS. RESULTS: The final quality assessment framework includes 81 questions, 67 (83%) of which impact the scores of 4 overarching quality aspects. After testing with people with low health literacy, these aspects were phrased as "Healthy and safe," "Easy to use," "Secure data," and "Robust build." The scoring mechanism enables communication of the quality assessment results in a health app quality score and label, alongside a detailed report. Unstructured interviews with stakeholders revealed that evidence and third-party assessment are needed for health app uptake. The manufacturers considered the time needed to complete the assessment and gather evidence (2-4 days) acceptable. Publication of CEN-ISO/TS 82304-2:2021 Health software - Part 2: Health and wellness apps - Quality and reliability was approved in May 2021 in a nearly unanimous vote by 34 national SDOs, including 6 of the 10 most populous countries worldwide. CONCLUSIONS: A useful and usable international standard for health app quality assessment was developed. Its quality, approval rate, and early use provide proof of its potential to become the trusted, commonly used global framework. The framework will help manufacturers enhance and efficiently demonstrate the quality of health apps, consumers, and health care professionals to make informed decisions on health apps. It will also help insurers to make reimbursement decisions on health apps.

Outcomes in extremely low birth weight (≤500 g) preterm infants: A Western Australian experience.

BACKGROUND AND AIM: Extremely preterm (EP) infant survival has significantly improved with advanced neonatal care; however outcomes of infants born with birth weight (BW) ≤500 g remain poor. We aimed to review outcomes of this cohort in our institution. METHODS: Retrospective study of all inborn preterm infants born at ≥22 weeks gestational age (GA) and weighing ≤500 g between January 2001-December 2017. Outcomes included short-term morbidity, mortality, neurodevelopmental impairment and growth up to five years of age. RESULTS: Of a total 438 eligible infants, 92 livebirths were admitted to intensive care [median (range) GA: 24 (22-30) weeks; median (IQR) BW: 427.5 (380-499) grams]. Majority [78/92 (84.7%)] were small for gestational age (SGA). In 50% of non-survivors, median (IQR) age of death was 3.5 (1-17.5) days with no late deaths. Medical morbidities were common. Follow-up, including standardised cognitive assessments, was available for 41/46 (89%) infants. At a median age of 5.06 years, 17/41 (41.5%) had moderate-severe disability; non-statistically higher in SGA compared to appropriate for gestational age/AGA (48.6% vs. 33.3%) group. Cerebral palsy (4/41; 10%), deafness needing amplification (1/41; 2.4%) were noted. Weight (32/41, 78%) and height (27/41, 66%) of most children remained at >2 SD below normal. CONCLUSIONS: In a cohort of preterm infants weighing ≤500 g at birth, 50% survived after admission to intensive care. Medical morbidities were common and 54% were free from moderate to severe disability at five years. SGA infants had higher rates (48.6%) of moderate to severe disability. Ongoing suboptimal growth in childhood is common.

Effect of cumulative dexamethasone dose in preterm infants on neurodevelopmental and growth outcomes: a Western Australia experience.

OBJECTIVE: Comparing the long-term neurodevelopmental and growth outcomes of lower and higher cumulative dexamethasone exposure in preterm infants ventilated for a minimum cumulative duration of 7 days. DESIGN: A retrospective cohort medical chart review of infants born in Western Australia <29 weeks' gestation between January 2007 and May 2016 who were mechanically ventilated >7 days. INTERVENTION: No dexamethasone (controls) or a total cumulative dexamethasone dose of <2 mg/kg (lower) and ≥2 mg/kg (higher). MAIN OUTCOME MEASURES: Long-term disability at 2 and 5 years and growth measurement outcomes at 2 years of age. RESULTS: Dexamethasone was given to 104 infants (66 with cumulative dose <2 mg/kg; 38 with cumulative dose ≥2 mg/kg), and 324 infants were controls. There was no difference in odds of long-term disability in infants with any dexamethasone exposure compared with controls (aOR: 0.90, 95% CI 0.34 to 2.02, p=0.784). No difference in long-term disability was found between the lower and higher groups (p=0.494). The prevalence of cerebral palsy (Gross Motor Functional Classification System level ≥2) between the control, lower and high-dose groups did not differ significantly (5.8% vs 4.0% vs 0%). The higher dose group had lower mean weight z-score (mean effect: -0.83, 95% CI: -1.54 to -0.01, p=0.023), height z-score (mean effect: -0.63, 95% CI: -12.5 to -0.01, p=0.048) and head circumference z-score (mean effect: -0.65, 95% CI: -1.25 to -0.05, p=0.035) compared with controls. CONCLUSIONS: In our cohort, dexamethasone use was not associated with increased odds of long-term disability. Dexamethasone use was associated with lower growth measurements compared with controls.

Protocol for assessing whether cognition of preterm infants <29 weeks' gestation can be improved by an intervention with the omega-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA): a follow-up of a randomised controlled trial.

INTRODUCTION: Docosahexaenoic acid (DHA) is an omega-3 (n-3) fatty acid that accumulates into neural tissue during the last trimester of pregnancy, as the fetal brain is undergoing a growth spurt. Infants born <29 weeks' gestation are deprived the normal in utero supply of DHA during this period of rapid brain development. Insufficient dietary DHA postnatally may contribute to the cognitive impairments common among this population. This follow-up of the N-3 fatty acids for improvement in respiratory outcomes (N3RO) randomised controlled trial aims to determine if enteral DHA supplementation in infants born <29 weeks' gestation during the first months of life improves cognitive development at 5 years of age corrected for prematurity. METHODS AND ANALYSIS: N3RO was a randomised controlled trial of enteral DHA supplementation (60 mg/kg/day) or a control emulsion (without DHA) in 1273 infants born <29 weeks' gestation to determine the effect on bronchopulmonary dysplasia (BPD). We showed that DHA supplementation did not reduce the risk of BPD and may have increased the risk.In this follow-up at 5 years' corrected age, a predefined subset (n=655) of children from five Australian sites will be invited to attend a cognitive assessment with a psychologist. Children will be administered the Wechsler Preschool and Primary Scale of Intelligence (fourth edition) and a measure of inhibitory control (fruit stroop), while height, weight and head circumference will be measured.The primary outcome is full-scale IQ. To ensure 90% power, a minimum of 592 children are needed to detect a four-point difference in IQ between the groups.Research personnel and families remain blinded to group assignment. ETHICS AND DISSEMINATION: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/17/WCHN/187). Caregivers will give informed consent prior to taking part in this follow-up study. Findings of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12612000503820.

Early Moves: a protocol for a population-based prospective cohort study to establish general movements as an early biomarker of cognitive impairment in infants.

INTRODUCTION: The current diagnostic pathways for cognitive impairment rarely identify babies at risk before 2 years of age. Very early detection and timely targeted intervention has potential to improve outcomes for these children and support them to reach their full life potential. Early Moves aims to identify early biomarkers, including general movements (GMs), for babies at risk of cognitive impairment, allowing early intervention within critical developmental windows to enable these children to have the best possible start to life. METHOD AND ANALYSIS: Early Moves is a double-masked prospective cohort study that will recruit 3000 term and preterm babies from a secondary care setting. Early Moves will determine the diagnostic value of abnormal GMs (at writhing and fidgety age) for mild, moderate and severe cognitive delay at 2 years measured by the Bayley-4. Parents will use the Baby Moves smartphone application to video their babies' GMs. Trained GMs assessors will be masked to any risk factors and assessors of the primary outcome will be masked to the GMs result. Automated scoring of GMs will be developed through applying machine-based learning to the data and the predictive value for an abnormal GM will be investigated. Screening algorithms for identification of children at risk of cognitive impairment, using the GM assessment (GMA), and routinely collected social and environmental profile data will be developed to allow more accurate prediction of cognitive outcome at 2 years. A cost evaluation for GMA implementation in preparation for national implementation will be undertaken including exploring the relationship between cognitive status and healthcare utilisation, medical costs, health-related quality of life and caregiver burden. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Medical Research Ethics Committee of Joondalup Health Services and the Health Service Human Research Ethics Committee (1902) of Curtin University (HRE2019-0739). TRIAL REGISTRATION NUMBER: ACTRN12619001422112.