BACKGROUND:Maternal omega-3 fatty acid status can influence gestational length, with low omega-3 status associated with increased preterm birth risk. However, the underlying mechanisms remain unclear. Oxylipin derivatives are plausible mediators of gestational timing and preterm birth risk. This review evaluates whether studies combining an omega-3 exposure or intervention with oxylipin profiling provide mechanistic insights into gestational length or preterm birth risk. METHODS:Randomised controlled trials (RCTs) and observational studies in pregnant women that included an omega-3 intervention or recorded omega-3 exposure, with oxylipins quantified by liquid chromatography coupled with mass spectrometry (LC-MS), were systematically reviewed. RESULTS:Two studies were identified that included an omega-3 intervention and quantification of oxylipins by LC-MS, both nested within the same parent trials. One study examined associations between oxylipins and gestational outcomes and reported that specific lipoxygenase derived oxylipins measured in early pregnancy were associated with higher risk of spontaneous preterm birth. The other study evaluated changes in oxylipin profiles in response to omega-3 supplementation but did not assess associations with gestational length or preterm birth. CONCLUSIONS:Available evidence is insufficient to clarify relationships between omega-3 status, preterm birth or gestational length. Limited findings suggest that select oxylipins may be associated with spontaneous preterm birth risk, but evidence remains hypothesis generating. Further well-designed studies using standardised LC-MS methods and broader oxylipin profiling are needed.

BACKGROUND:Despite evidence that omega-3 supplementation reduces early preterm birth, population-level data on the distribution of fatty acids in pregnancy are limited. Statewide early-pregnancy screening data were used to describe serum fatty acid profiles. METHODS:We analysed serum fatty acid classes (saturated, monounsaturated, omega-6 polyunsaturated fatty acids [PUFA] and omega-3 PUFA) from women in South Australia's Omega-3 Test-and-Treat Program (Apr 2021-Apr 2025). Samples collected at <20 weeks' gestation were measured by gas chromatography (% total fatty acids). Total omega-3 PUFA (alpha-linolenic acid + eicosapentaenoic acid [EPA] + docosapentaenoic acid + docosahexaenoic acid [DHA]) was classified as low (<3.7%), moderate (3.7-4.3%) or sufficient (>4.3%). RESULTS:Among 26,389 samples, omega-6 PUFA was highest (median 36.9%), followed by saturated fatty acids (31.6%), monounsaturated fatty acids (26.2%), and omega-3 PUFA (4.4%). Total omega-3 PUFA, DHA and EPA were right-skewed, whereas arachidonic acid (AA) had a narrow distribution. Overall, 16.1% were classified as low total omega-3, 26.7% were moderate and 57.2% sufficient. Compared with samples classified as sufficient, those with low omega-3 had higher linoleic acid (29.0%vs 26.9%) and slightly lower AA (6.2%vs 7.1%). The clinically validated cut-off for low omega-3 (<3.7%) was similar to one standard deviation below the cohort mean (mean -1 SD = 3.47%). CONCLUSION:Around one in six samples had low serum total omega-3 status. These data quantify early-pregnancy serum fatty acid profiles and demonstrate the clinically validated low omega-3 cut-off lies in the lower tail of the population distribution, providing context for biomarker-guided screening in pregnancy.

INTRODUCTION:Spaceflight presents unique challenges to ocular health, as visual disturbances such as dry eye symptoms have been frequently reported by astronauts. Matrix metalloproteinases (MMPs), a family of extracellular matrix-degrading enzymes, are known mediators of ocular surface inflammation and tissue remodeling on Earth, particularly in dry eye disease. This review explores the potential role of MMPs in spaceflight-associated ocular conditions, including spaceflight-associated dry eye syndrome and spaceflight-associated neuro-ocular syndrome. METHODS:We searched literature on topics relating to metallomatrix proteins and spaceflight using databases PubMed, MedLine, Embase, and Central from inception to April 2025. RESULTS:Although there are limited studies on direct measurements of tear MMPs during spaceflight, indirect clinical evidence and analog studies suggest that microgravity, radiation, and systemic inflammation may upregulate MMP expression. This contributes to epithelial barrier disruption and impaired wound healing. Rodent models and simulated microgravity experiments further support the mechanosensitive regulation of MMPs across various tissues. DISCUSSION:Given the safety and accessibility of tear collection, MMPs may be useful biomarkers for assessing ocular and systemic changes in astronauts. Understanding MMP expression and regulation in space may inform preventive strategies to preserve vision during long-duration missions. Stephanian B, Ong J, Lee R, Gibson R, Berdahl J, Waisberg E, Mader TH, Lee AG. Ocular matrix metalloproteinases in spaceflight. Aerosp Med Hum Perform. 2026; 97(1):47-54.

BACKGROUND:Concentrations of the long-chain polyunsaturated fatty acids, in particular, the ω-3 (n-3) fatty acid DHA and the ω-6 fatty acid arachidonic acid (AA), decrease in infant blood during the first days after very preterm birth. OBJECTIVES:This study aimed to explore factors associated with blood DHA and AA concentrations of very preterm infants receiving standard care, in the days following birth. METHODS:We examined the fatty acid composition of whole blood samples collected on cards at 0-6 d after birth, from a cross-sectional study of 1174 infants born <29 weeks of gestation in Australia, New Zealand, and Singapore. RESULTS:Considerable variation was observed in the proportions of blood AA (1.4%-18.0%) and DHA (0.4%-5.7%) concentrations. Infant blood DHA status was not associated with gestational age at birth, but AA was lower by 0.11% for each week of gestation (95% CI: -0.07%, 0.15%). There was an inverse relationship between age of sampling after birth and DHA (0.07% lower per day; 95% CI: 0.04%, 0.09%) and AA (0.09% lower; 95% CI: 0.04%, 0.14%). A concomitant positive relationship was observed between days after birth and the fatty acids present in the intravenous lipid emulsion administered: ω-6 linoleic acid (range: 2.1%-35.1%) and ω-9 oleic acid (range: 12.2%-52.9%). CONCLUSIONS:Preterm infants whose blood was sampled later after birth have lower DHA and AA status relative to those sampled earlier after birth; samples taken at later timepoints are concurrently higher in the fatty acids of linoleic acid and oleic acid, which are the major compositional components of intravenous lipid emulsions routinely administered to preterm infants. The results support calls to develop intravenous feeds closely matching the fatty acid composition of infant blood at birth. The N3RO Trial is registered at the Australian New Zealand Clinical Trial Registry as ACTRN12612000503820 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000503820).

Objective: To evaluate the feasibility and early adoption of the Omega-3 Test-and-Treat Program, a targeted intervention to reduce preterm birth in women with low omega-3 levels, implemented within routine antenatal care. Design: A prospective implementation study using the Quality Enhancement Research Initiative (QUERI) framework, conducted between April 19, 2021, and June 30, 2022. Setting: Antenatal care settings in South Australia, leveraging the South Australia (SA) Pathology, South Australian Serum Antenatal Screening (SAMSAS) program. Participants: Pregnant women with singleton pregnancies <20 weeks' gestation undergoing antenatal screening and healthcare providers responsible for ordering and facilitating omega-3 testing. Intervention: A structured program to identify women with low omega-3 levels in early pregnancy and provide evidence-based supplementation guidance to reduce the risk of preterm birth. Main Outcome Measures: Program feasibility (uptake and fidelity), representativeness of early adopters compared to the broader population, adherence to program criteria (singleton pregnancies <20 weeks' gestation), and omega-3 status distribution. Results: A total of 4,801 omega-3 tests were reported by SA Pathology, with consistent uptake over time. Women tested were demographically and clinically comparable to those not tested. Among early adopters, 702 (14.7%) had low, 1,638 (34.2%) moderate, and 2,442 (51.1%) sufficient omega-3 levels. Program fidelity was high across 5057 omega-3 lab samples with 4,935 (97.6%) analysed within the standard 72-hour timeframe. Adherence to testing criteria was strong, with only 33 (0.7%) samples from pregnancies >20 weeks' and 58 (1.2%) from multiple pregnancies. Conclusion: Early evaluations show the Omega-3 Test-and-Treat Program is feasible and integrates effectively into routine antenatal care. This real-world approach demonstrates strong potential to reduce preterm birth rates through targeted nutritional intervention, supporting its scalability and broader implementation. ### Competing Interest Statement MM served as President of the International Society for the Study of Fatty Acids and Lipids (ISSFAL) from 2021 to 2024 (unpaid role). RG holds a patent titled "Stabilising and analysing fatty acids in a biological sample stored on solid media" (Patent ID AU2013209278). KB served as a member of a Preterm Birth Prevention Trial Data Safety and Monitoring Board (unpaid role). LY received funding from Societe des Produits Nestle for a separate analysis of data from the ORIP trial to identify women likely to benefit from omega-3 supplementation, which was unrelated to this work. All other authors declare no relevant disclosures. ### Funding Statement This work was supported by a project grant from the Thyne Reid Foundation and the Hospital Research Foundation (THRF), as well as an Australian National Health and Medical Research Council (NHMRC) Centre of Research Excellence Grant (APP1135155). The ORIP trial was funded through an NHMRC project grant (APP1050468). MM and PM were supported by Australian NHMRC Investigator Grants (APP2016756 and APP1172870). KB received support from a Women's and Children's Hospital Foundation MS McLeod Postdoctoral Fellowship. The funders had no role in the design, conduct, or analysis of this work. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This work was approved by the Women's and Children's Health Network Human Research Ethics Committee (HREC/20/WCHN/138). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data for this study will not be shared, as we do not have permission from the participants or ethics approval to do so.

Astronauts can develop a distinct collection of neuro-ophthalmic findings during long duration spaceflight, collectively known as Spaceflight Associated Neuro-ocular Syndrome (SANS). These clinical characteristics include optic disc edema, hyperopic refractive shifts, globe flattening, and chorioretinal folds, which may pose a health risk for future space exploration. Obtaining knowledge of SANS and countermeasures for its prevention is crucial for upcoming crewed space missions and warrants a multidisciplinary approach. This review examines the potential causes and countermeasures of SANS, including space anticipation glasses, lower body negative pressure, venoconstrictive thigh cuffs, impedance threshold devices, translaminar pressure gradient modulation, centrifugation, artificial gravity, pharmaceuticals, and precision nutritional supplementation. This paper highlights future research directions for understanding the genetic, anthropometric, behavioral, and environmental susceptibilities to SANS as well as how to use terrestrial analogs for testing future mitigation strategies.

OBJECTIVE:To assess the feasibility of embedding omega-3 fatty acid testing and targeted supplementation (the Omega-3 Test-and-Treat Program) into routine antenatal care to reduce the risk of preterm birth. STUDY DESIGN:Prospective implementation evaluation study, using the Quality Enhancement Research Initiative (QUERI) framework. SETTING, PARTICIPANTS:Women with singleton pregnancies undergoing routine antenatal screening during early pregnancy (before 20 weeks' gestation) and their health care providers, South Australia, 19 April 2021 - 30 June 2022. INTERVENTION:Addition of omega-3 fatty acid testing option to SA Pathology test referral forms for the South Australian Maternal Serum Antenatal Screening (SAMSAS) program, with the aim of identifying women with low omega-3 fatty acid levels during early pregnancy and providing evidence-based supplementation guidance for reducing the risk of preterm birth. MAIN OUTCOME MEASURES:Program feasibility (uptake and fidelity); representativeness of women tested for omega-3 fatty acid status; and omega-3 fatty acid status, by proportion of total serum fatty acids (low, < 3.7%; moderate, 3.7-4.3%; sufficient, > 4.3%). RESULTS:A total of 4801 requests for omega-3 fatty acid tests (26.1% of 18 362 SAMSAS referrals) were submitted to SA Pathology during the initial implementation phase of the Omega-3 Test-and-Treat Program. The monthly number of test requests increased from 15 (2.4% of 627 SAMSAS referrals) in April 2021 to 340 (29.4% of 1156 SAMSAS referrals) in June 2022. The socio-demographic and clinical characteristics of women referred for omega-3 fatty acid testing were similar to those for women who were not. Serum samples were insufficient for omega-3 fatty acid testing in 19 cases; of the 4782 tests performed, omega-3 fatty acid levels were low in 702 (14.7%), moderate in 1638 (34.2%), and sufficient in 2442 tests (51.1%). Of 5057 samples received by the Omega-3 Laboratory, 4935 (97.6%) were analysed within 72 hours. Thirty-three of 4801 omega-3 fatty acid test referrals (0.7%) were for women beyond 20 weeks of pregnancy; 58 referrals (1.2%) were for women with non-singleton pregnancies. CONCLUSION:The Omega-3 Test-and-Treat Program is a feasible approach to reducing the risk of preterm birth with a targeted nutritional intervention that could be integrated into routine antenatal care in Australia.

Background: Enteral high-dose docosahexaenoic acid (DHA) may be required for neurodevelopment, including cognition, of extremely preterm infants. High-level summative evidence is lacking. Objectives: This study aims to examine associations between enteral high-dose DHA during the neonatal period and neurodevelopment in infants born ≤29 wk of gestation. Methods: The following databases were searched (from inception to 11 April, 2024): CINAHL, Cochrane Library, Embase, Medline, Scopus, and Web of Science. Eligible randomized controlled trials (RCTs) in infants born ≤29 wk, assessing direct enteral administration ≥ 40 mg/kg/d DHA, or breast milk/formula with DHA ≥ 0.60% total fatty acids, reporting neurodevelopmental outcomes. Two reviewers independently screened articles, extracted data, and assessed quality using the Cochrane Handbook guidance. Data were pooled using fixed or random-effect meta-analyses. The primary outcome was global cognitive scores from a standardized test. Results: We screened 1978 articles and included 3 high-quality RCTs (2028 infants born ≤29 wk). Enteral high-dose DHA was not associated with overall differences in global cognition scores at a corrected age (CA) of 18–36 mo [3 RCTs, 638 children, mean difference (MD) 0.67; 95% confidence interval (CI): –1.80, 3.15; P = 0.59; I2 = 0%] or CA of 5–7 y (2 RCTs, 852 children; MD: 2.22; 95% CI: –0.14, 4.57; P = 0.06; I2 = 33%); however, benefit was observed in the largest RCT with a direct enteral emulsion (656 children, CA of 5 y, MD 3.45; 95% CI: 0.38, 6.52; P = 0.03). Associations with most secondary outcomes were not seen; however, high-dose DHA was associated with reduced mild motor (3 RCTs, CA of 18–36 mo) and cognitive (2 RCTs, CA of 5–7 y) impairment. No negative impacts were observed. Conclusions: Enteral high-dose DHA in extremely preterm infants was not associated with differences in global cognition scores on meta-analysis; however, higher scores were observed with the use of a direct emulsion. Results support contemporary recommendations.This trial was registered at PROSPERO as CRD42022382744 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382744).

Bisphenol analogues have been shown to have similar estrogenic activity to that of BPA and may affect fetal development. However, no human studies have examined the effects of perinatal exposure to emerging bisphenol alternatives [bisphenol G, bisphenol M, and bisphenol BP (BPBP)] on small for gestational age (SGA) and how placental function may mediate the relationship. Here, 13 urinary bisphenol analogues were detected in 1054 contemporary pregnant women, and BPA was still the most dominant congener. Logistic regressions identified BPA and its traditional alternatives [bisphenol B (BPB), bisphenol E (BPE), bisphenol Z, and bisphenol AP (BPAP)] as being associated with an elevated risk of SGA (all ORs > 1.80, P < 0.05). In contrast, the emerging substitutes, despite high occurrences, all showed much attenuated risk. Mixture effect models Bayesian kernel machine regression and quantile-based g-computation demonstrated that coexposure to bisphenols was strongly correlated with SGA risk (OR = 2.70, P < 0.001), with BPA and the conventional substitutes (BPB, BPE, and BPAP) as primary effect drivers, outweighing the effect from emerging substitutes. Finally, mediation analysis revealed that the placental function index estriol mediated the relationship between exposure and SGA, dominated by BPBP (25.4%). Our findings provide new epidemiological evidence that early BPA alternatives may pose a higher risk for offspring development than those emerging alternatives, potentially via mediation by compromised placental function. Future toxicity assessments and validation studies in other settings on these emerging bisphenols are needed.

BACKGROUND:Preterm birth (< 37 weeks gestation) is a leading cause of infant morbidity and mortality, yet the underlying causes remain unknown in many cases. Environmental exposures, including endocrine-disrupting chemicals such as phthalates, have been implicated in preterm birth risk. Phthalates are commonly used as plasticisers in consumer products, resulting in widespread human exposure. While some studies suggest an association between maternal phthalate exposure and reduced gestational length, findings remain inconsistent. This study aimed to investigate the relationship between urinary phthalate metabolite concentrations and gestational length in an Australian pregnancy cohort. METHODS:This prospective cohort study was nested within the Omega-3 to Reduce the Incidence of Prematurity (ORIP) trial. A total of 605 women with singleton pregnancies from South Australia provided urine samples between 22- and 26-weeks' gestation for phthalate metabolite analysis. Thirteen phthalate metabolites were quantified using liquid chromatography-tandem mass spectrometry. Gestational age at birth was determined from medical records. Linear regression models assessed associations between phthalate concentrations and gestational length, adjusting for maternal characteristics including age, BMI, socioeconomic status, education, smoking, and alcohol consumption. RESULTS:Phthalate metabolites were detected in > 99% of urine samples, with the highest concentrations observed for mono-ethyl phthalate (MEP), mono-isobutyl phthalate (MiBP), and mono-butyl phthalate (MBP). There was no evidence of an association between phthalate exposure and gestational length in either unadjusted or adjusted analyses. No significant association was found between phthalate exposure and preterm birth risk. CONCLUSIONS:Despite widespread phthalate exposure, no clear link was identified between maternal phthalate levels and shortened gestation in this Australian cohort. However, continued surveillance is needed to monitor emerging plasticiser exposures and inform public health policies on maternal and infant health. TRIAL REGISTRATION NUMBER:Australian New Zealand Clinical Trials Registry number, ACTRN12613001142729. Date of registration: 27/09/2013.

BACKGROUND: This article documents the stability of photorefractive keratectomy (PRK) and laser -assisted in situ keratomileusis (LASIK) in two astronauts during 6-mo missions to the International Space Station. CASE REPORTS: Ocular examinations including visual acuity, cycloplegic refraction, slit lamp examination, corneal topography, central corneal thickness, optical biometry (axial length/keratometry), applanation tonometry, and dilated fundus examination were performed on each astronaut before and after their missions, and in-flight visual acuity testing was done on flight day 30, 90, and R-30 (30 d before return). They were also questioned regarding visual changes during flight. DISCUSSION: We documented stable vision in both PRK and LASIK astronauts during liftoff, entry into microgravity, 6 mo on the International Space Station, descent, and landing. Our results suggest that both PRK and LASIK are stable and well tolerated during long -duration spaceflight.

Per- and polyfluoroalkyl substances (PFASs) can disrupt lipid metabolism, and changes in cord blood fatty acid composition have been observed in small newborns. Emerging evidence suggests that exposure to PFASs during pregnancy is linked to decreased newborn size, although the evidence is not consistent. The modifying effect of fatty acids on the associations of gestational PFAS exposure with newborn size is still unknown. Here we show that the nutritional status of the fetus, as indicated by the level of fatty acids in the cord blood, mitigates the adverse effects of gestational PFAS exposure on the size of the newborn. Our study confirms the adverse developmental effects of PFASs and identifies emerging short-chain PFASs as the primary drivers of reduced newborn size, despite their lower exposure burden compared to legacy PFASs. Additionally, we find the protective role of cord blood fatty acids, suggesting potential strategies for mitigating the detrimental effects of emerging environmental exposures on human health. Our findings provide new evidence of the potential toxicity of emerging PFASs and call for further toxicity evaluations of these pollutants for regulatory purposes. Future studies should consider the complex interaction between exposure and nutrition within the human body, particularly during the first thousand days of life, to promote lifelong health.

BACKGROUND:Infant formulas are typically manufactured using skimmed milk, whey proteins, and vegetable oils, which excludes milk fat globule membranes (MFGM). MFGM contains polar lipids, including sphingomyelin (SM). OBJECTIVE:The objective of this study was comparison of infant plasma SM and acylcarnitine species between infants who are breastfed or receiving infant formulas with different fat sources. METHODS:In this explorative study, we focused on SM and acylcarnitine species concentrations measured in plasma samples from the TIGGA study (ACTRN12608000047392), where infants were randomly assigned to receive either a cow milk-based infant formula (CIF) with vegetable oils only or a goat milk-based infant formula (GIF) with a goat milk fat (including MFGM) and vegetable oil mixture to the age ≥4 mo. Breastfed infants were followed as a reference group. Using tandem mass spectrometry, SM species in the study formulas and SM and acylcarnitine species in plasma samples collected at the age of 4 mo were analyzed. RESULTS:Total SM concentrations (∼42 μmol/L) and patterns of SM species were similar in both formulas. The total plasma SM concentrations were not different between the formula groups but were 15 % (CIF) and 21% (GIF) lower in the formula groups than in the breastfed group. Between the formula groups, differences in SM species were statistically significant but small. Total carnitine and major (acyl) carnitine species were not different between the groups. CONCLUSIONS:The higher total SM concentration in breastfed than in formula-fed infants might be related to a higher SM content in human milk, differences in cholesterol metabolism, dietary fatty acid intake, or other factors not yet identified. SM and acylcarnitine species composition in plasma is not closely related to the formula fatty acid composition. This trial was registered at Australian New Zealand Clinical Trials Registry as ACTRN12608000047392.

The objective of the study was to assess the accumulation of omega-3 (n-3) fats and the sensory quality of scrambled eggs from two strains of laying hens (brown and white) given omega-3 enriched diets. The design of this research was a completely randomized block design, with a 3 × 2 factorial. A total of 24 Hy-Line brown and 24 Hy-Line white were fed three experimental diets. The alphalinolenic acid (18:3n3, ALA) levels of the dietary treatments were either low (0.3%), moderate (3.0%), or high (6.0%) with the linoleic acid (18:2n6, LA) level kept constant at approximately 4%en. The results showed that dietary supplementation of ALA enhanced n-3 fats and had no impact (P>0.05) on sensory properties including oily odour, butter aroma, sulphur aroma, taste, flavour, or off-flavour of scrambled eggs. Diets high in ALA resulted in Scrambled eggs with less intense egg aroma compared to those given diets with low or moderate ALA. Eggs of brown hens had a significantly stronger egg aroma, butter flavour, and sulphur flavour (P<0.05) compared to white eggs. In conclusion, the dietary inclusion of 3.0% ALA was discovered to be optimum with respect to the accumulation of n-3 fats and the sensory properties of the eggs.

The aim of this study was to evaluate the levels of omega-3 (n-3) and omega-6 (n-6) fatty acids in egg and the ratio of n-6/n-3 of white eggs produced by laying hens (Hy-Line white) fed diets enriched with n-3 fats. In this study, alpha-linolenic acid (ALA) levels of the dietary treatments ranged from 0.3 to 6% energy. Grain-based diets containing a low linoleic acid (LA) content were selected to prepare a basal diet to optimize the conversion of ALA into n-3 long chain polyunsaturated fatty acids (LCPUFA). The results showed that the level of all n-3 LCPUFA in eggs improved (P < 0.01) by increasing the levels of dietary ALA. Importantly, eggs produced from laying hens fed diets containing 6%en ALA significantly increased (P < 0.01) the total of n-3 fats by approximately nine-fold. Diets enriched with ALA significantly reduced (P < 0.01) the ratio of n-6/n-3 of the eggs. The n-6/n-3 ratio of eggs decreased from 7.17% in the 0.3%en ALA diet to 1.29% in the 6%en ALA diet. In conclusion, white laying hens fed ALA-enriched diets produced eggs higher in n-3 fatty acids and lower n-6/n-3 ratio, which provides an alternative n-3 rich food for consumers and have beneficial health effects.

The cause of death in people affected by sickle cell disease (SCD) is often challenging to define as prior studies have used retrospective or administrative data for analysis. We used a prospective longitudinal registry to assess mortality and clinical co-morbidities among subjects enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. At enrollment, we collected the following data: patient-reported demographics, SCD phenotype, baseline laboratory values, comorbidities, and current medications. Subjects were followed for a median of 4.7 years before the present analysis. The relationship of clinical co-morbidities (at time of enrollment) to mortality was determined using survival analysis, adjusting for SCD phenotype and gender. There was a total of 2439 people with SCD enrolled in the SCDIC registry. One hundred and twenty-eight participants (5%) died during the observation period (2017-2022). Six people died from trauma and were excluded from further analysis. Proximate cause of death was unwitnessed in 17% of the deaths, but commonest causes of death include cardiac (18%), acute chest or respiratory failure (11%), sudden unexplained death (8%). Enrollment characteristics of the individuals who died (n = 122) were compared to those of survivors (n = 2317). Several co-morbidities at enrollment increased the odds of death on univariate analysis. All co-morbidities were included in a multivariable model. After backward elimination, iron overload, pulmonary hypertension, and depression, remained statistically significant predictors of the risk of death. SCD reduces life expectancy. Improved comprehensive and supportive care to prevent end-organ damage and address comorbidities is needed for this population.

We read with great interest the article by Tidwell and colleagues[1][1] entitled "Longitudinal Changes in Cerebral Perfusion, Perivascular Space Volume, and Ventricular Volume in a Healthy Cohort Undergoing a Spaceflight Analog" published recently in the American Journal of Neuroradiology . We

Objective To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit.Design Individual participant data meta-analysis.Data sources Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset.Eligibility criteria for selecting studies Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model.Results The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, -18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R2) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of -22.3 g (Allen cohort), -33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (-154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making.Conclusions The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required.Trial registration PROSPERO CRD42019135045