Repeat or single-dose lentiviral vector administration to mouse lungs? It's all about the timing.

Lentiviral vectors are attractive delivery vehicles for cystic fibrosis gene therapy owing to their low immunogenicity and ability to integrate into the host cell genome, thereby producing long-term, stable gene expression. Nonetheless, repeat dosing may be required to increase initial expression levels, and/or boost levels when they wane. The primary aim of this study was to determine if repeat dosing of a VSV-G pseudotyped LV vector delivered into mouse lungs is more effective than a single dose. C57Bl/6 mouse lungs were conditioned with lysophosphatidylcholine, followed one-hour later by a LV vector carrying the luciferase reporter gene, using six different short-term (≤1 wk) and long-term (>1 wk) dosing schedules. Luciferase expression was quantified using bioluminescence imaging over 12 months. Most dosing schedules produced detectable bioluminescence over the 12-month period, but the shorter intervals (≤1 wk) produced higher levels of flux than the longest interval (five doses at least 1-month apart). Ex vivo lung analysis at 12 months showed that the estimated mean flux for the group that received two doses 1-week apart was significantly greater than the single dose group and the two groups that received doses over a period greater than 1-week. These results suggest that early consecutive multiple doses are more effective at improving gene expression in mouse lungs at 12 months, than longer repeat dosing intervals.

Assessment of Mobilization Potential of Per- and Polyfluoroalkyl Substances for Soil Remediation.

This study investigated the mobilization of a wide range of per- and polyfluoroalkyl substances (PFASs) present in aqueous film-forming foams (AFFFs) in water-saturated soils through one-dimensional (1-D) column experiments with a view to assessing the feasibility of their remediation by soil desorption and washing. Results indicated that sorption/desorption of most of the shorter-carbon-chain PFASs (C ≤ 6) in soil reached greater than 99% rapidly─after approximately two pore volumes (PVs) and were well predicted by an equilibrium transport model, indicating that they will be readily removed by soil washing technologies. In contrast, the equilibrium model failed to predict the mobilization of longer-chain PFASs (C ≥ 7), indicating the presence of nonequilibrium sorption/desorption (confirmed by a flow interruption experiment). The actual time taken to attain 99% sorption/desorption was up to 5 times longer than predicted by the equilibrium model (e.g., ∼62 PVs versus ∼12 PVs predicted for perfluorooctane sulfonate (PFOS) in loamy sand). The increasing contribution of hydrophobic interactions over the electrostatic interactions is suggested as the main driving factor of the nonequilibrium processes. The inverse linear relationship (R2 = 0.6, p < 0.0001) between the nonequilibrium mass transfer rate coefficient and the Freundlich sorption coefficient could potentially be a useful means for preliminary evaluation of potential nonequilibrium sorption/desorption of PFASs in soils.

Comparing the Leaching Behavior of Per- and Polyfluoroalkyl Substances from Contaminated Soils Using Static and Column Leaching Tests.

Soil contaminated with aqueous film-forming foams (AFFFs) containing per- and polyfluoroalkyl substances (PFASs) at firefighting training sites has become a major concern worldwide. To date, most studies have focused on assessing soil-water partitioning behavior of PFASs and the key factors that can affect their sorption, whereas PFASs leaching from contaminated soils have not yet been widely investigated. This study evaluated the leaching and desorption of a wide range of PFASs from twelve contaminated soils using the Australian Standard Leaching Procedure (ASLP), the U.S. EPA Multiple Extraction Procedure (MEP), and Leaching Environmental Assessment Framework (LEAF). All three leaching tests provided a similar assessment of PFAS leaching behavior. Leaching of PFASs from soils was related to C-chain lengths and their functional head groups. While short-chain (CF2 ≤ 6) PFASs were easily desorbed and leached, long-chain PFASs were more difficult to desorb. PFASs with a carboxylate head group were leached more readily and to a greater extent than those with a sulfonate or sulfonamide head group. Leaching of long-chain PFASs was pH-dependent where leaching increased at high pH, while leaching of short-chain PFASs was less sensitive to pH. Comparing different leaching tests showed that the results using the alkaline ASLP were similar to the cumulative MEP data and the former might be more practical for routine use than the MEP. No single soil property was adequately able to describe PFAS leaching from the soils. Overall, the PFAS chemical structure appeared to have a greater effect on PFAS leaching from soil than soil physicochemical properties.

Relative importance of metabolic syndrome components for developing gestational diabetes.

PURPOSE: To assess the independent and joint contribution of the individual components of metabolic syndrome, and known risk factors for gestational diabetes (GDM), on risk of GDM. METHODS: Two thousand nine hundred and fifteen women from Australia and New Zealand, who participated in The Screening for Pregnancy Endpoints Study (SCOPE), were included. Using the SCOPE clinical data set and biomarkers obtained at 14-16 weeks' gestation, a logistic regression model was fitted to the binary outcome GDM, with individual metabolic syndrome components (waist circumference, blood pressure, glucose, HDL-C, triglycerides), recruitment site, and other established factors associated with GDM. Hierarchical partitioning was used to assess the relative contribution of each variable. RESULTS: Of the 2915 women, 103 women (3.5%) developed GDM. The deviance explained by the logistic regression model containing all variables was 18.65% and the AUC was 0.809. Seventy percent of the independent effect was accounted for by metabolic syndrome components. The highest independent relative contribution to GDM was circulating triglycerides (17 ± 3%), followed by waist circumference (13 ± 3%). Glucose and maternal BMI contributed 12 ± 2% and 12 ± 3%, respectively. The remaining factors had an independent relative contribution of < 10%. CONCLUSION: Triglyceride concentrations had the highest independent relative importance for risk of GDM. Increased focus for lowering triglycerides as an important risk factor for GDM is warranted.

Phenotypic Characterization and Comparison of Cystic Fibrosis Rat Models Generated Using CRISPR/Cas9 Gene Editing.

Animal models of cystic fibrosis (CF) are essential for investigating disease mechanisms and trialing potential therapeutics. This study generated two CF rat models using clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9 gene editing. One rat model carries the common human Phe508del (ΔF508) CF transmembrane conductance regulator (CFTR) mutation, whereas the second is a CFTR knockout model. Phenotype was characterized using a range of functional and histologic assessments, including nasal potential difference to measure electrophysiological function in the upper airways, RNAscope in situ hybridization and quantitative PCR to assess CFTR mRNA expression in the lungs, immunohistochemistry to localize CFTR protein in the airways, and histopathologic assessments in a range of tissues. Both rat models revealed a range of CF manifestations, including reduced survival, intestinal obstruction, bioelectric defects in the nasal epithelium, histopathologic changes in the trachea, large intestine, and pancreas, and abnormalities in the development of the male reproductive tract. The CF rat models presented herein will prove useful for longitudinal assessments of pathophysiology and therapeutics.

The BlastGen study: a randomized controlled trial of blastocyst media supplemented with granulocyte-macrophage colony-stimulating factor.

RESEARCH QUESTION: Does Embryogen®/BlastGen™ culture medium improve live birth rates compared with standard culture medium for women undergoing IVF and intracytoplasmic sperm injection (ICSI) with poor prognosis. DESIGN: Randomized clinical trial. A total of 100 couples undergoing IVF/ICSI were randomly allocated to having their inseminated oocytes incubated in either Embryogen®/BlastGen™ sequential culture media or standard Cleavage/Blastocyst sequential culture media for 5 days (ClinicalTrials.gov Identifier: NCT02305420). RESULTS: No statistically significant difference in live birth rate was found between the control group and the Embryogen®/BlastGen™ group (17 [34%] versus 11 [22%], respectively) (OR 0.55; 95% CI 0.22 to 1.32; P = 0.18). After adjustment for maternal age, body mass index and fertilization procedure, the blastulation rate reduced (40.6 ± 26.5 versus 24.6 ± 26.7; RR 0.70, CI 0.52 to 0.95; P < 0.05), and grade of the embryo transferred (OR 0.35, CI 0.16 to 0.77; P < 0.01) when Embryogen®/BlastGen™ medium was used. CONCLUSION: A significant reduction in day-5 embryo outcome parameters was found using Embryogen®/BlastGen™ compared with standard medium, and insufficient evidence of a difference in pregnancy outcomes. Taking into consideration the small samples size, study limitations and strict inclusion criteria of this single-centre study, further research is needed to determine the efficacy of Embryogen®/BlastGen™ medium in couples undergoing IVF/ICSI.

The deleterious effects of cannabis during pregnancy on neonatal outcomes.

OBJECTIVES: To evaluate whether cannabis use during pregnancy is associated with adverse neonatal outcomes that are independent of cigarette smoking. DESIGN: Prospective cohort study. SETTING: Adelaide (Australia), Auckland (New Zealand), Cork (Ireland), and Leeds, London and Manchester (United Kingdom). PARTICIPANTS: 5610 pregnant nulliparous women with low risk pregnancies recruited for the Screening for Pregnancy Endpoints (SCOPE) study, November 2004 - February 2011. At 14-16 weeks of pregnancy, women were grouped by self-reported cannabis use. MAIN OUTCOME MEASURES: Infant birthweight, head circumference, birth length, gestational age, and severe neonatal morbidity or mortality. RESULTS: 314 women (5.6%) reported using cannabis in the 3 months before or during their pregnancy; 97 (31%) stopped using it before and 157 (50%) during the first 15 weeks of pregnancy, while 60 (19%) were still using cannabis at 15 weeks. Compared with babies of mother who had never used cannabis, infants of those who still used it at 15 weeks had lower mean values for birthweight (adjusted mean difference [aMD], -127 g; 95% CI, -238 to -17 g), head circumference (aMD, -0.5 cm; 95% CI, -0.8 to -0.1 cm), birth length (aMD, -0.8 cm; 95% CI, -1.4 to -0.2 cm), and gestational age at birth (aMD, -8.1 days; 95% CI, -12.1 to -4.0 days). The differences for all outcomes except gestational age were greater for women who used cannabis more than once a week than for those who used it less frequently. CONCLUSIONS: Continuing to use cannabis during pregnancy is an independent risk factor for poorer neonatal outcomes.

Limited uptake of ulcerative colitis "treat-to-target" recommendations in real-world practice.

BACKGROUND AND AIMS: A "treat-to-target" approach has been proposed for ulcerative colitis (UC), with a target of combined clinical and endoscopic remission. The aim of the study was to evaluate the extent to which proposed targets are achieved in real-world care, along with clinician perceptions and potential challenges. METHODS: A multicentre, retrospective, cross-sectional review of patients with UC attending outpatient services in South Australia was conducted. Clinical and objective assessment of disease activity (endoscopy, histology, and/or biomarkers) was recorded. A survey evaluated gastroenterologists' perceptions of treat to target in UC. Statistical analysis included logistic regression and Fisher's exact tests. RESULTS: Of 246 patients with UC, 61% were in clinical remission (normal bowel habit and no rectal bleeding), 35% in clinical and endoscopic remission (Mayo endoscopic sub-score ≤ 1), and 16% in concordant clinical, endoscopic, and histological (Truelove and Richards' Index) remission. Rather than disease-related factors (extent/activity), clinician-related factors dominated outcome. Hospital location and the choice of therapy predicted combined clinical and endoscopic remission (OR 3.6, 95% CI 1.6-8.7, P < 0.001; OR 3.3, 95% CI 1.1-12.5, P = 0.04, respectively). Clinicians used C-reactive protein more often than endoscopy as a biomarker for disease activity (75% vs 47%, P < 0.001). In the survey, 45/61 gastroenterologists responded, with significant disparity between clinician estimates of targets achieved in practice and real-world data (P < 0.001 for clinical and endoscopic remission). CONCLUSIONS: Most patients with UC do not achieve composite clinical and endoscopic remission in "real-world" practice. Clinician uptake of proposed treat-to-target guidelines is a challenge to their implementation.

Reliability and accuracy of six hand-held blood lactate analysers.

The reliability and accuracy of five portable blood lactate (BLa) analysers (Lactate Pro, Lactate Pro2, Lactate Scout+, Xpress™, and Edge) and one handheld point-of-care analyser (i-STAT) were compared to a criterion (Radiometer ABL90). Two devices of each brand of analyser were assessed using 22 x 6 mL blood samples taken from five subjects at rest and during exercise who generated lactate ranging ~1-23 mM. Each sample was measured simultaneously ~6 times on each device. Reliability was assessed as the within-sample standard deviation (wsSD) of the six replicates; accuracy as the bias compared with the ABL90; and overall error (the root mean squared error (√MSE)) was calculated as the square root of (wsSD(2) and bias(2)). The √MSE indicated that both the Edge and Xpress had low total error (~0-2 mM) for lactate concentrations <15 mM, whereas the Edge and Lactate Pro2 were the better of the portable analysers for concentrations >15 mM. In all cases, bias (negative) was the major contribution to the √MSE. In conclusion, in a clinical setting where BLa is generally <15 mM the Edge and Xpress devices are relevant, but for athlete testing where peak BLa is important for training prescription the Edge and Lactate Pro2 are preferred. Key pointsThe reliability of five common portable blood lactate analysers were generally <0.5 mM for concentrations in the range of ~1.0-10 mM.For all five portable analysers, the analytical error within a brand was much smaller than the biological variation in blood lactate (BLa).Compared with a criterion blood lactate analyser, there was a tendency for all portable analysers to under-read (i.e. a negative bias), which was particularly evident at the highest concentrations (BLa ~15-23 mM).The practical application of these negative biases would overestimate the ability of the athlete and prescribe a training intensity that would be too high.

Bird community responses to the edge between suburbs and reserves.

New insights into community-level responses at the urban fringe, and the mechanisms underlying them, are needed. In our study, we investigated the compositional distinctiveness and variability of a breeding bird community at both sides of established edges between suburban residential areas and woodland reserves in Canberra, Australia. Our goals were to determine if: (1) community-level responses were direct (differed with distance from the edge, independent of vegetation) or indirect (differed in response to edge-related changes in vegetation), and (2) if guild-level responses provided the mechanism underpinning community-level responses. We found that suburbs and reserves supported significantly distinct bird communities. The suburban bird community, characterised by urban-adapted native and exotic species, had a weak direct edge response, with decreasing compositional variability with distance from the edge. In comparison, the reserve bird community, characterised by woodland-dependent species, was related to local tree and shrub cover. This was not an indirect response, however, as tree and shrub cover was not related to edge distance. We found that the relative richness of nesting, foraging and body size guilds also displayed similar edge responses, indicating that they underpinned the observed community-level responses. Our study illustrates how community-level responses provide valuable insights into how communities respond to differences in resources between two contrasting habitats. Further, the effects of the suburban matrix penetrate into reserves for greater distances than previously thought. Suburbs and adjacent reserves, however, provided important habitat resources for many native species and the conservation of these areas should not be discounted from continued management strategies.

Dairy-based preexercise meal does not affect gut comfort or time-trial performance in female cyclists.

Some athletes avoid dairy in the meal consumed before exercise due to fears about gastrointestinal discomfort. Regular exclusion of dairy foods may unnecessarily reduce intake of high quality proteins and calcium with possible implications for body composition and bone health. This study compared the effects of meals that included (Dairy) or excluded (Control) dairy foods on gastric comfort and subsequent cycling performance. Well-trained female cyclists (n = 32; mean ± SD; 24.3 ± 4.1 y; VO(2peak) 57.1 ± 4.9 ml/kg/min) completed two trials (randomized cross-over design) in which they consumed a meal (2 g/kg carbohydrate and 54 kJ/kg) 2 hr before a 90-min cycle session (80 min at 60% maximal aerobic power followed by a 10-min time trial; TT). The dairy meal contained 3 servings of dairy foods providing ~1350 mg calcium. Gut comfort and palatability were measured using questionnaires. Performance was measured as maximum mean power during the TT (MMP10(min)). There was no statistical or clinical evidence of an effect of meal type on MMP10(min) with a mean difference (Dairy - Control) of 4 W (95% CI [-2, 9]). There was no evidence of an association between pretrial gut comfort and meal type (p = .15) or between gut comfort delta scores and meal type postmeal (p = .31), preexercise (p = .17) or postexercise (p = .80). There was no statistical or clinical evidence of a difference in palatability between meal types. In summary, substantial amounts of dairy foods can be included in meals consumed before strenuous cycling without impairing either gut comfort or performance.

Interruptions in healthcare: Modeling dynamic processes and effects at a team level.

Interruptions are associated with increases in medical errors amongst healthcare professionals, yet interventions to reduce interruptions have not been widely successful. While interruptions can be problematic for the interruptee, they may be necessary for the interrupter to maintain patient safety. To understand the emergent effects of interruptions within a dynamic environment, we develop a computational model that describes how nurses make decisions about interruptions and the effects those decisions have at a team level. Simulations reveal the dynamic interplay between urgency, task importance, the cost of being interrupted and team efficiency, depending on the consequences of clinical or procedural error, and shed light on the ways that the risks from interruptions can be better managed.

Spatial and temporal trends of 64 pesticides and their removal from Australian wastewater.

Pesticides are necessary for the control of pest plant, fungi and insect species. After application, they may find their way into waste streams, such as municipal sewage, where their spatio-temporal distribution has not been well characterised. To further understand the spatio-temporal distribution and to evaluate potential sources and fate after treatment, 64 pesticides were analysed in matched influents and effluents of 22 wastewater treatment plants (WWTPs) from across Australia. The pesticides consisted of 30 herbicides and 8 herbicide metabolites or transformation products, 16 insecticides and 10 fungicides. The samples were 1084 24-hr composite samples pooled into 113 samples. Pools represented two influent and one effluent pools at each of 22 sites in 2019, as well as two pools per year from 2009 to 2021 for an 11-year long-term temporal trend at a subset of two locations. The total population served by the 22 sites was equivalent to ~41 % of the Australian population. Of the 64 pesticides, 25 were detected in influent, with highest influent concentrations up to 100 µg/L and effluent concentrations up to 16 µg/L for the herbicide 2,4-D. The total mass of pesticides was extrapolated to Australia, suggesting ~33 t of the targeted pesticides entered WWTP influent annually nation-wide, with 14 t emitted into effluents annually. Long-term trends varied by analyte and for carbendazim decreases over time, may be related to restrictions in use. Risk quotients (RQs) were calculated for 14 analytes in the effluent. 35 % had an RQ above one, indicating a potential environmental risk. Fipronil had the highest RQ (49) at Site 6. The population-normalized mass loads of pesticides were site-specific, and in some cases correlated with land use attributes suggestive of point sources. This reflects a need to better characterise sources to enable prevention, or possible pre-treatment of pesticide-containing wastewater entering municipal sewage streams.

Bisphenols and phthalates in Australian wastewater: A statistical approach for estimating contributions from diffuse and point sources.

Chemicals associated with plastics, such as bisphenols and phthalates, enter sewerage from both diffuse (domestic/commercial) and point (industrial) sources. In this study, we aimed to devise a conservative, statistical baseline to estimate contributions from these source types when sampling of specific sources is not possible. Population-normalised mass loads of two bisphenols and nine phthalates were estimated in wastewater samples from 22 sewage treatment plants (STPs) in 2019. Two multiday (10 and 7 day) pools were created for each STP. Baseline (diffuse) release thresholds were set at the mean of the first quartile (Q1) plus 10 times the standard deviation (STDV) of this quartile [Q1 mean + (10 x STDV)], with contributions over this considered to come from point sources. Chemicals with at least one population-normalised mass load more than three times their baseline were classified as point-source dominant and the remaining as diffuse-source dominant. Eleven of the twelve chemicals examined were detected above limits of quantification in all wastewater samples. Bisphenol A (BPA), bisphenol S (BPS), di-isononyl phthalate (DiNP) and di-methyl phthalate (DMP) were classified as point-source dominant chemicals. The total annual mass loads entering STPs across Australia were estimated to be 4.2 tonnes/year from diffuse sources and 4.5 tonnes/year from point sources for bisphenols, and 47 tonnes/year from diffuse sources and 5.9 tonnes/year from point sources for phthalates.

Calibration of a microporous polyethylene tube passive sampler for polar organic compounds in wastewater effluent.

Water resources are vulnerable to contamination from polar organic compounds (POCs) originating from sources such as wastewater effluent. Two configurations of a microporous polyethylene tube (MPT) passive sampler were investigated for the time-integrative detection and quantification of POCs in effluent. One configuration contained the polymeric reversed phase sorbent Strata-X (SX) and the other Strata-X suspended in agarose gel (SX-Gel). These were deployed for up to 29 days and analysed for forty-nine POCs including pesticides, pharmaceuticals and personal care products (PPCPs) together with illicit drugs. Complementary composite samples were collected on days 6, 12, 20 and 26 representing the previous 24 h. Thirty-eight contaminants were detected in composite samples and MPT extracts, with MPT sampling rates (Rs) for 11 pesticides and 9 PPCPs/drugs ranging from 0.81 to 10.32 mL d-1 in SX and 1.35-32.83 mL d-1 in SX-Gel. Half-times to equilibrium of contaminants with the SX and SX-Gel equipped samplers ranged from two days to >29 days. MPT (SX) samplers were also deployed at 10 wastewater treatment effluent discharge sites across Australia for 7 days (again with complementary composite samples), to validate the sampler performance under varying conditions. Extracts from these MPTs detected 48 contaminants in comparison with 46 in composite samples, with concentrations ranging from 0.1 to 138 ng mL-1. An advantage of the MPT was preconcentration of contaminants, resulting in extract levels often markedly above instrument analytical detection limits. The validation study demonstrated a high correlation between accumulated contaminant mass in the MPTs and wastewater concentrations from composite samples (r2 > 0.70, where concentrations in composite samples were > 3× LOD). The MPT sampler shows promise as a sensitive tool for detecting POCs at trace levels in wastewater effluent and also quantifying these levels if temporal concentration variations are not significant.

The efficacy of soil washing for the remediation of per- and poly-fluoroalkyl substances (PFASs) in the field.

This paper aims to describe the performance of a soil washing plant (SWP) for remediating a per- and poly-fluoroalkyl substances (PFASs)-contaminated soil with a high clay content (61%). The SWP used both physical and chemical processes; fractionation of the soil particles by size and partitioning of PFASs into the aqueous phase to remove PFASs from the soil. Contaminated water was treated in series with granulated activated carbon (GAC) and ion-exchange resin and reused within the SWP. Approximately 2200 t (dry weight) of PFAS-contaminated soil was treated in 25 batches of 90 t each, with a throughput of approximately 11 t soil/hr. Efficiency of the SWP was measured by observed decreases in total and leachable concentrations of PFASs in the soil. Average removal efficiencies (RE) were up to 97.1% for perfluorocarboxylic acids and 94.9% for perfluorosulfonic acids. REs varied among different PFASs depending on their chemistry (functional head group, carbon chain length) and were independent of the total PFAS concentrations in each soil batch. Mass balance analysis found approximately 90% of the PFAS mass in the soil was transferred to the wash solution and > 99.9% of the PFAS mass in the wash solution was transferred onto the GAC without any breakthrough.

Protocol for a nested case-control study design for omics investigations in the Environmental Determinants of Islet Autoimmunity cohort.

Background: The Environmental Determinants of Islet Autoimmunity (ENDIA) pregnancy-birth cohort investigates the developmental origins of type 1 diabetes (T1D), with recruitment between 2013 and 2019. ENDIA is the first study in the world with comprehensive data and biospecimen collection during pregnancy, at birth and through childhood from at-risk children who have a first-degree relative with T1D. Environmental exposures are thought to drive the progression to clinical T1D, with pancreatic islet autoimmunity (IA) developing in genetically susceptible individuals. The exposures and key molecular mechanisms driving this progression are unknown. Persistent IA is the primary outcome of ENDIA; defined as a positive antibody for at least one of IAA, GAD, ZnT8 or IA2 on two consecutive occasions and signifies high risk of clinical T1D.Method: A nested case-control (NCC) study design with 54 cases and 161 matched controls aims to investigate associations between persistent IA and longitudinal omics exposures in ENDIA. The NCC study will analyse samples obtained from ENDIA children who have either developed persistent IA or progressed to clinical T1D (cases) and matched control children at risk of developing persistent IA. Control children were matched on sex and age, with all four autoantibodies absent within a defined window of the case's onset date. Cases seroconverted at a median of 1.37 years (IQR 0.95, 2.56). Longitudinal omics data generated from approximately 16,000 samples of different biospecimen types, will enable evaluation of changes from pregnancy through childhood.Conclusions: This paper describes the ENDIA NCC study, omics platform design considerations and planned univariate and multivariate analyses for its longitudinal data. Methodologies for multivariate omics analysis with longitudinal data are discovery-focused and data driven. There is currently no single multivariate method tailored specifically for the longitudinal omics data that the ENDIA NCC study will generate and therefore omics analysis results will require either cross validation or independent validation.KEY MESSAGESThe ENDIA nested case-control study will utilize longitudinal omics data on approximately 16,000 samples from 190 unique children at risk of type 1 diabetes (T1D), including 54 who have developed islet autoimmunity (IA), followed during pregnancy, at birth and during early childhood, enabling the developmental origins of T1D to be explored.

The Australian Feeding Infants and Toddler Study (OzFITS 2021): Breastfeeding and Early Feeding Practices.

The Australian Feeding Infants and Toddler Study 2021 (OzFITS 2021) is a nationwide survey of Australian caregivers' infant and toddler feeding practices. Here, we describe breastfeeding rates and duration, use of breastmilk substitutes, and introduction of complementary (solid) foods, including common food allergens. Caregivers (n = 1140) were recruited by a digital marketing company and were interviewed using a structured telephone questionnaire to obtain information. Breastfeeding was initiated in 98% of infants, but the duration of exclusive breastfeeding to six months was less than 1%. Nearly 40% of children continued to receive breastmilk beyond one year, with 10% of toddlers receiving breastmilk at two years. One-quarter of infants were introduced to solid foods between 4 to 5 months, and nearly all infants had received solid foods by 7 months. New guidelines encourage the early introduction of potential food allergens to reduce the risk of allergy, and by 12 months, over 90% of children had been given eggs and peanuts. One-third of children received no breastmilk substitutes during their first year. One-third of infants first received breastmilk substitutes following birth and before discharge from the hospital. Of these infants, 30% ceased breastmilk substitute use after discharge. Our findings suggest a high rate of continued breastfeeding with 44% receiving breastmilk beyond 1 year. One approach to increase the duration of exclusive breastfeeding is to reduce breastmilk substitute use while in hospital.

Associations of Maternal Milk Feeding With Neurodevelopmental Outcomes at 7 Years of Age in Former Preterm Infants.

Importance: Maternal milk feeding may have unique long-term neurodevelopmental benefits in very preterm infants. Objective: To examine the extent to which maternal milk feeding after very preterm birth is associated with cognitive, academic, and behavioral outcomes at school age. Design, Setting, and Participants: This prospective cohort study assessed 586 infants born at less than 33 weeks' gestation at 5 Australian perinatal centers and enrolled in the Docosahexaenoic Acid for Improvement of Neurodevelopmental Outcomes study (January 1, 2001, to December 31, 2005) who were evaluated at a corrected age of 7 years. The statistical analysis was completed on January 19, 2022. Exposures: Maternal milk intake, including mean volume (milliliters per kilogram per day) during neonatal hospitalization and total duration (in months). Main Outcomes and Measures: Neurodevelopmental outcomes at 7 years of age were (1) IQ (Wechsler Abbreviated Scale of Intelligence), (2) academic achievement (Wide Range Achievement Test, Fourth Edition), (3) symptoms of attention-deficit/hyperactivity disorder (ADHD) (Conners Third Edition ADHD Index, parent reported), (4) executive function (Behavior Rating Inventory of Executive Functioning, parent reported), and (5) behavior (Strengths and Difficulties Questionnaire, parent reported). Results: A total of 586 infants (mean [SD] gestational age at birth, 29.6 [2.3] weeks; 314 male [53.6%]) born to 486 mothers (mean [SD] age, 30.6 [5.5] years; 447 [92.0%] White) were included. Mean (SD) maternal milk intake in the neonatal intensive care unit was 99 (48) mL/kg daily, and mean (SD) maternal milk duration was 5.1 (5.4) months. Mean (SD) full-scale IQ was 98.5 (13.3) points. After covariate adjustment, higher maternal milk intake during the neonatal hospitalization was associated with higher performance IQ (0.67 points per additional 25 mL/kg daily; 95% CI, 0.10-1.23 points), reading scores (1.14 points per 25 mL/kg daily; 95% CI, 0.39-1.89 points), and math scores (0.76 points per 25 mL/kg daily; 95% CI, 0.14-1.37 points) and fewer ADHD symptoms (-1.08 points per 25 mL/kg daily; 95% CI, -1.96 to -0.20 points). Longer duration of maternal milk intake was associated with higher reading (0.33 points per additional month; 95% CI, 0.03-0.63 points), spelling (0.31 points per month; 95% CI, 0.01-0.62 points), and math (0.30 points per month; 95% CI, 0.03-0.58 points) scores. Maternal milk was not associated with improved full-scale IQ, verbal IQ, executive function, or behavior. Most associations were stronger among infants born at lower gestational ages, particularly less than 30 weeks (interaction P values <.01). Conclusions and Relevance: In this cohort study of preterm infants, maternal milk feeding during the neonatal hospitalization and after discharge were associated with better school-age performance IQ and academic achievement and with a reduction in ADHD symptoms, particularly among infants born at less than 30 weeks' gestation.