Neurodevelopmental outcomes at 2 years in children who received sildenafil therapy in utero: The STRIDER randomised controlled trial.

OBJECTIVE: Severe early-onset fetal growth restriction (FGR) causes stillbirth, neonatal death and neurodevelopmental impairment. Poor maternal spiral artery remodelling maintains vasoactive responsiveness but is susceptible to treatment with sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, which may improve perinatal outcomes. DESIGN: Superiority, double-blind randomised controlled trial. SETTING: A total of 20 UK fetal medicine units. POPULATION: Pregnancies affected by FGR, defined as an abdominal circumference below the tenth centile with absent end-diastolic flow in the umbilical artery between 22+0 and 29+6 weeks of gestation. METHODS: Treatment with sildenafil (25 mg three times/day) or placebo until delivery or 32 weeks of gestation. MAIN OUTCOME MEASURES: All infants alive at hospital discharge were assessed for cardiovascular function and cognitive, speech/language and neuromotor impairment at 2 years of age. The primary outcome was survival without cerebral palsy or neurosensory impairment, or a Bayley-III composite score of >85. RESULTS: In total, 135 women were randomised between November 2014 and July 2016 (70 to sildenafil and 65 to placebo). We previously published that there was no improvement in time to delivery or perinatal outcomes with sildenafil. In all, 75 babies (55.5%) were discharged alive, with 61 infants eligible for follow-up (32 sildenafil and 29 placebo). One infant died (placebo), three mothers declined and ten mothers were uncontactable. There was no difference in neurodevelopment or blood pressure following treatment with sildenafil. Infants who received sildenafil had a larger head circumference at 2 years of age (median difference 49.2 cm, IQR 46.4-50.3, vs 47.2 cm, 95% CI 44.7-48.9 cm). CONCLUSIONS: Sildenafil therapy did not prolong pregnancy or improve perinatal outcomes and did not improve infant neurodevelopment in FGR survivors. Therefore, sildenafil should not be prescribed for this condition.

Resilience during lockdown: a longitudinal study investigating changes in behaviour and attitudes among older females during COVID-19 lockdown in the UK.

In order to slow the spread of COVID-19, on March 23, 2020, a strict lockdown was implemented in the UK. This was followed by alternating periods of less restrictive lockdowns until most public health restrictions were lifted in the summer of 2021. While these measures were necessary, they significantly affected people's daily activities, lifestyles, and mental well-being.This paper presents a longitudinal research study that focused on females aged 55 + in the UK, aiming to understand how COVID-19 and the subsequent 15-month period of lockdowns affected their lifestyles and emotions. The study collected data through online surveys, where respondents reported the frequency and mode of access to activities, and their positive and negative emotional experiences during distinct study phases that encompassed both lockdown and less strict periods.In contrast to previous studies highlighting vulnerabilities for females and the elderly during lockdowns, this research found that the studied group maintained an overall positive outlook throughout the study period and successfully adapted to the lockdowns by increasing their engagement in certain activities, in particular, activities like 'getting active'. In addition, our findings indicate rapid adaptive behaviour change towards many online activities, such as cultural activities. However, the study also revealed negative emotions and a decrease in some activities during the second lockdown in 2020 and the subsequent lockdowns in 2021, underscoring the challenges inherent in prolonged periods of confinement. In addition, the study found negative affect associated with some activities, including working and studying from home.The findings provide valuable insights into how females aged over 55 coped with stressful circumstances, which can inform the development of resilient and mental health-conscious public health policies and responses in preparation for future pandemics or other hazards.

Genome-wide DNA methylation analysis of discordant monozygotic twins reveals consistent sites of differential methylation associated with congenital heart disease.

BACKGROUND: Despite being essentially genetically identical, monozygotic (MZ) twins can be discordant for congenital heart disease (CHD), thus highlighting the importance of in utero environmental factors for CHD pathogenesis. This study aimed to identify the epigenetic variations between discordant MZ twin pairs that are associated with CHD at birth. METHODS: Cord blood of CHD-discordant MZ twins from the Chongqing Longitudinal Twin Study Cohort was subjected to whole-genome bisulfite sequencing, then validated by MeDIP-qPCR and qRT-PCR. RESULTS: 379 DMRs mapped to 175 differentially methylated genes (DMGs) were associated with CHD. Functional enrichment analysis identified these DMGs are involved in histone methylation, actin cytoskeleton organization, the regulation of cell differentiation, and adrenergic signaling in cardiomyocytes. Of note, SPESP1 and NOX5 were hypermethylated in CHD, and associated with lower gene expression levels. CONCLUSIONS: Specific DNA methy (DNAm) variations in cord blood were associated with CHD, thus illustrating new biomarkers and potential interventional targets for CHD. TRIAL REGISTRATION: ChiCTR-OOC-16008203, registered on 1 April 2016 at the Chinese Clinical Trial Registry.

Airborne grass pollen and thunderstorms influence emergency department asthma presentations in a subtropical climate.

BACKGROUND: Grass pollen is considered a major outdoor aeroallergen source worldwide. It is proposed as a mechanism for thunderstorm asthma that lightning during thunderstorms promotes electrical rupture of pollen grains that leads to allergic airway inflammation. However, most evidence of associations between grass pollen and asthma comes from temperate regions. The objective of this study was to investigate short-term associations between airborne grass pollen exposure and asthma emergency department presentations in a subtropical population. METHODS: Episode level public hospital presentations for asthma (2016-2020) were extracted for greater Brisbane, Australia, from Queensland Health's Emergency Data Collection. Concentrations of airborne pollen were determined prospectively using a continuous flow volumetric impaction sampler. Daily time series analysis using a generalised additive mixed model were applied to determine associations between airborne grass pollen concentrations, and lightning count data, with asthma presentations. RESULTS: Airborne grass pollen showed an association with asthma presentations in Brisbane; a significant association was detected from same day exposure to three days lag. Grass pollen exposure increased daily asthma presentations up to 48.5% (95% CI: 12%, 85.9%) in female children. Lightning did not modify the effect of grass pollen on asthma presentations, however a positive association was detected between cloud-to-cloud lightning strikes and asthma presentations (P = 0.048). CONCLUSION: Airborne grass pollen exposure may exacerbate symptoms of asthma requiring urgent medical care of children and adults in a subtropical climate. This knowledge indicates an opportunity for targeted management of respiratory allergic disease to reduce patient and health system burden. For the first time, an influence of lightning on asthma was detected in this context. The outcomes support a need for continued pollen monitoring and surveillance of thunderstorm asthma risk in subtropical regions.

Interventions affecting the nitric oxide pathway versus placebo or no therapy for fetal growth restriction in pregnancy.

BACKGROUND: Fetal growth restriction (FGR) is a condition of poor growth of the fetus in utero. One of the causes of FGR is placental insufficiency. Severe early-onset FGR at < 32 weeks of gestation occurs in an estimated 0.4% of pregnancies. This extreme phenotype is associated with a high risk of fetal death, neonatal mortality, and neonatal morbidity. Currently, there is no causal treatment, and management is focused on indicated preterm birth to prevent fetal death. Interest has risen in interventions that aim to improve placental function by administration of pharmacological agents affecting the nitric oxide pathway causing vasodilatation. OBJECTIVES: The objective of this systematic review and aggregate data meta-analysis is to assess the beneficial and harmful effects of interventions affecting the nitric oxide pathway compared with placebo, no therapy, or different drugs affecting this pathway against each other, in pregnant women with severe early-onset FGR. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (16 July 2022), and reference lists of retrieved studies. SELECTION CRITERIA: We considered all randomised controlled comparisons of interventions affecting the nitric oxide pathway compared with placebo, no therapy, or another drug affecting this pathway in pregnant women with severe early-onset FGR of placental origin, for inclusion in this review. DATA COLLECTION AND ANALYSIS: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. MAIN RESULTS: We included a total of eight studies (679 women) in this review, all of which contributed to the data and analysis. The identified studies report on five different comparisons: sildenafil compared with placebo or no therapy, tadalafil compared with placebo or no therapy, L-arginine compared with placebo or no therapy, nitroglycerin compared with placebo or no therapy and sildenafil compared with nitroglycerin. The risk of bias of included studies was judged as low or unclear. In two studies the intervention was not blinded. The certainty of evidence for our primary outcomes was judged as moderate for the intervention sildenafil and low for tadalafil and nitroglycerine (due to low number of participants and low number of events). For the intervention L-arginine, our primary outcomes were not reported. Sildenafil citrate compared to placebo or no therapy (5 studies, 516 women) Five studies (Canada, Australia and New Zealand, the Netherlands, the UK and Brazil) involving 516 pregnant women with FGR were included. We assessed the certainty of the evidence as moderate. Compared with placebo or no therapy, sildenafil probably has little or no effect on all-cause mortality (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.80 to 1.27, 5 studies, 516 women); may reduce fetal mortality (RR 0.82, 95% CI 0.60 to 1.12, 5 studies, 516 women), and increase neonatal mortality (RR 1.45, 95% CI 0.90 to 2.33, 5 studies, 397 women), although the results are uncertain for fetal and neonatal mortality as 95% confidence intervals are wide crossing the line of no effect. Tadalafil compared with placebo or no therapy (1 study, 87 women) One study (Japan) involving 87 pregnant women with FGR was included. We assessed the certainty of the evidence as low. Compared with placebo or no therapy, tadalafil may have little or no effect on all-cause mortality (risk ratio 0.20, 95% CI 0.02 to 1.60, one study, 87 women); fetal mortality (RR 0.11, 95% CI 0.01 to 1.96, one study, 87 women); and neonatal mortality (RR 0.89, 95% CI 0.06 to 13.70, one study, 83 women). L-Arginine compared with placebo or no therapy (1 study, 43 women) One study (France) involving 43 pregnant women with FGR was included. This study did not assess our primary outcomes. Nitroglycerin compared to placebo or no therapy (1 studies, 23 women) One study (Brazil) involving 23 pregnant women with FGR was included. We assessed the certainty of the evidence as low. The effect on the primary outcomes is not estimable due to no events in women participating in both groups. Sildenafil citrate compared to nitroglycerin (1 study, 23 women) One study (Brazil) involving 23 pregnant women with FGR was included. We assessed the certainty of the evidence as low. The effect on the primary outcomes is not estimable due to no events in women participating in both groups. AUTHORS' CONCLUSIONS: Interventions affecting the nitric oxide pathway probably do not seem to influence all-cause (fetal and neonatal) mortality in pregnant women carrying a baby with FGR, although more evidence is needed. The certainty of this evidence is moderate for sildenafil and low for tadalafil and nitroglycerin. For sildenafil a fair amount of data are available from randomised clinical trials, but with low numbers of participants. Therefore, the certainty of evidence is moderate. For the other interventions investigated in this review there are insufficient data, meaning we do not know whether these interventions improve perinatal and maternal outcomes in pregnant women with FGR.

Predictors of Knowledge, Attitude, and Practice (KAP) Towards Family Planning (FP) Among Pregnant Women in Fiji.

OBJECTIVE: This study aimed to determine the predictors of Knowledge, Attitude and Practice (KAP) towards Family Planning (FP) among pregnant Fijian women. METHODS: A cross-sectional study was conducted over two months in 2019 with adult pregnant women attending the Antenatal Clinic (ANC) at Ba Mission Hospital (BMH), Fiji. Data was collected using a self-administrated questionnaire. Statistical analysis included correlation tests and regression analysis in determining predictors of KAP. RESULTS: 240 pregnant women participated in this study with a mean age of 26.02 (± SD = 4.13). The results showed a moderate level of knowledge (mean 14.95, SD ± 3.15), positive attitude (mean 20.56, SD ± 5.68), and good practice (mean 4.97, SD ± 1.73). Linear regression identified that women with more than seven children had a knowledge score of 3.65, lower than null parity (t value = -2.577, p = 0.011). Women aged 20 to 24 had a 6.47 lower attitude score than women aged 18 to 19 (t value = -2.142, p = 0.033). Women in defacto relationships had a 2.12 lower attitude score compared to the married category (t value = -2.128, p = 0.034). Fijian women of Indian descent had a 1.98 lower attitude score than the I Taukei women (t value = -2.639, p = 0.009). Women aged 30-34 had 2.41 lower practice scores than those aged 18-19 (t value = -2.462, p = 0.015). CONCLUSION: This study found a medium knowledge of FP among pregnant women. These findings support a recommendation for further research to implement effective strategies.

Child Maltreatment and Long-Term Physical and Mental Health Outcomes: An Exploration of Biopsychosocial Determinants and Implications for Prevention.

Child maltreatment rates remain unacceptably high and rates are likely to escalate as COVID-related economic problems continue. A comprehensive and evidence-building approach is needed to prevent, detect and intervene where child maltreatment occurs. This review identifies key challenges in definitions, overviews the latest data on prevalence rates, reviews risk and protective factors, and examines common long-term mental health outcomes for children who experience maltreatment. The review takes a systems approach to child maltreatment outcomes through its focus on the overall burden of disease, gene-environment interactions, neurobiological mechanisms and social ecologies linking maltreatment to mental ill-health. Five recommendations relating to the accurate measurement of trends, research on brain structures and processes, improving the reach and impact of teleservices for detecting, preventing and treating child maladjustment, community-based approaches, and building population-focused multidisciplinary alliances and think tanks are presented.

A novel role of FoxO3a in the migration and invasion of trophoblast cells: from metabolic remodeling to transcriptional reprogramming.

BACKGROUND: The forkhead box O3a protein (FoxO3a) has been reported to be involved in the migration and invasion of trophoblast, but its underlying mechanisms unknown. In this study, we aim to explore the transcriptional and metabolic regulations of FoxO3a on the migration and invasion of early placental development. METHODS: Lentiviral vectors were used to knock down the expression of FoxO3a of the HTR8/SVneo cells. Western blot, matrigel invasion assay, wound healing assay, seahorse, gas-chromatography-mass spectrometry (GC-MS) based metabolomics, fluxomics, and RNA-seq transcriptomics were performed. RESULTS: We found that FoxO3a depletion restrained the migration and invasion of HTR8/SVneo cells. Metabolomics, fluxomics, and seahorse demonstrated that FoxO3a knockdown resulted in a switch from aerobic to anaerobic respiration and increased utilization of aromatic amino acids and long-chain fatty acids from extracellular nutrients. Furthermore, our RNA-seq also demonstrated that the expression of COX-2 and MMP9 decreased after FoxO3a knockdown, and these two genes were closely associated with the migration/invasion progress of trophoblast cells. CONCLUSIONS: Our results suggested novel biological roles of FoxO3a in early placental development. FoxO3a exerts an essential effect on trophoblast migration and invasion owing to the regulations of COX2, MMP9, aromatic amino acids, energy metabolism, and oxidative stress.

The prevalence and associated factors of prenatal depression and anxiety in twin pregnancy: a cross-sectional study in Chongqing, China.

BACKGROUND: Pregnant women expecting twins are more likely to experience stress, which can lead to anxiety and depression. Our aim was to investigate the prevalence of prenatal anxiety and depressive symptoms in women with twin pregnancies and the associated factors. METHODS: In a cross-sectional survey, 210 women with twin pregnancies who satisfied the inclusion and exclusion criteria in two tertiary centers in Southwestern China were asked to complete a basic information form, the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS). To compare statistics with normal distribution in distinct characteristic groups, a paired t-test, and one-way ANOVA were utilized. Binary logistic step regression was used to analyze the associated factors of antenatal anxiety and depressive symptoms. RESULTS: The 210 women with twin pregnancies (age = 30.8 ± 4.2 years) were between 7 and 37 gestational weeks (29.2 ± 1.2 weeks), were typically well-educated (72.4% had a post-high-school degree), and reasonably affluent (88.1% were above the low-income cutoff). Among them, 34.8% had symptoms associated with clinical levels of anxiety, and 37.1% had symptoms indicating possible depression. The prevalence of co-morbid anxiety and depressive symptoms was 24.3%. Binary stepwise logistic regression analysis showed that previous health status and sleep disturbance during pregnancy were the associated factors of anxiety symptoms in women with twin pregnancies (P < 0.05), whereas age, previous health status, negative life events, and physical activity during pregnancy were the associated factors of depressive symptoms in women with twin pregnancies (P < 0.05). CONCLUSION: About one-third of women with twin pregnancies had symptoms of anxiety or depression; these were most strongly predicted by some modifiable factors, suggesting that early preventive mind-body interventions may be a promising strategy to protect against mental health issues for women with twin pregnancies.

The effects of gestational diabetes mellitus with maternal age between 35 and 40 years on the metabolite profiles of plasma and urine.

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance in pregnancy and without a history of diabetes mellitus. While there are limited metabolomic studies involving advanced maternal age in China, we aim to investigate the metabolomic profiling of plasma and urine in pregnancies complicated with GDM aged at 35-40 years at early and late gestation. METHODS: Twenty normal and 20 GDM pregnant participants (≥ 35 years old) were enlisted from the Complex Lipids in Mothers and Babies (CLIMB) study. Maternal plasma and urine collected at the first and third trimester were detected using gas chromatography-mass spectrometry (GC-MS). RESULTS: One hundred sixty-five metabolites and 192 metabolites were found in plasma and urine respectively. Urine metabolomic profiles were incapable to distinguish GDM from controls, in comparison, there were 14 and 39 significantly different plasma metabolites between the two groups in first and third trimester respectively. Especially, by integrating seven metabolites including cysteine, malonic acid, alanine, 11,14-eicosadienoic acid, stearic acid, arachidic acid, and 2-methyloctadecanoic acid using multivariant receiver operating characteristic models, we were capable of discriminating GDM from normal pregnancies with an area under curve of 0.928 at first trimester. CONCLUSION: This study explores metabolomic profiles between GDM and normal pregnancies at the age of 35-40 years longitudinally. Several compounds have the potential to be biomarkers to predict GDM with advanced maternal age. Moreover, the discordant metabolome profiles between the two groups could be useful to understand the etiology of GDM with advanced maternal age.

From proband to provider: is there an obligation to inform genetic relatives of actionable risks discovered through direct-to-consumer genetic testing?

Direct-to-consumer genetic testing is a growing phenomenon, fuelled by the notion that knowledge equals control. One ethical question that arises concerns the proband's duty to share information indicating genetic risks in their relatives. However, such duties are unenforceable and may result in the realisation of anticipated harm to relatives. We argue for a shift in responsibility from proband to provider, placing a duty on test providers in the event of identified actionable risks to relatives. Starting from Parker and Lucassen's (2004) 'joint account model', we adapt Kilbride's (2018) application of the rule of rescue and balance it against the relative's right not to know, placing responsibility on the providers of direct-to-consumer genetic testing. Where the risk of disease to a relative is actionable, we argue providers ought to share results even in the face of the proband's objections. Confidentiality issues are navigated by a pre-emptive consent model, whereby consumers agree to the sharing of certain information with their relatives ahead of testing and as a condition of testing. When a relative is informed, the proband's privacy is protected by maximal deidentification, and the rights of the relative are met by a stepwise approach to informing that allows them to decide how much information they receive.

How to design and implement a university-based COVID-19 testing programme? An evaluation of a novel RT-LAMP COVID-19 testing programme in a UK university.

BACKGROUND: Little is known about how asymptomatic testing as a method to control transmission of COVID-19 can be implemented, and the prevalence of asymptomatic infection within university populations. The objective of this study was to investigate how to effectively set-up and implement a COVID-19 testing programme using novel reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) technology and to quantify the scale of asymptomatic infection on a university campus. METHODS: An observational study to describe the set-up and implementation of a novel COVID-19 testing programme on a UK university campus between September and December 2020. RT-LAMP testing was used to identify asymptomatic cases. RESULTS: A total of 1,673 tests were performed using RT-LAMP during the study period, of which 9 were positive for COVID-19, giving an overall positivity rate of 0.54%, equivalent to a rate in the tested population of 538 cases per 100,000 over the duration of testing. All positive tests were found to be positive on RT-PCR testing, giving a false positive rate of 0%. CONCLUSIONS: This study shows that it is possible to rapidly setup a universal university testing programme for COVID-19 in collaboration with local healthcare providers using RT-LAMP testing. Positive results were comparable to those in the local population, though with a different peak of infection. Further research to inform the design of the testing programme includes focus groups of those who underwent testing and further interrogation of the demographics of those opting to be tested to identify potential access problems or inequalities.

Rodents on a high-fat diet born to mothers with gestational diabetes exhibit sex-specific lipidomic changes in reproductive organs.

Maternal gestatonal diabetes mellitus (GDM) and offspring high-fat diet (HFD) have been shown to have sex-specific detrimental effects on the health of the offspring. Maternal GDM combined with an offspring HFD alters the lipidomic profiles of offspring reproductive organs with sex hormones and increases insulin signaling, resulting in offspring obesity and diabetes. The pre-pregnancy maternal GDM mice model is established by feeding maternal C57BL/6 mice and their offspring are fed with either a HFD or a low-fat diet (LFD). Testis, ovary and liver are collected from offspring at 20 weeks of age. The lipidomic profiles of the testis and ovary are characterized using gas chromatography-mass spectrometry. Male offspring following a HFD have elevated body weight. In reproductive organs and hormones, male offspring from GDM mothers have decreased testes weights and testosterone levels, while female offspring from GDM mothers show increased ovary weights and estrogen levels. Maternal GDM aggravates the effects of an offspring HFD in male offspring on the AKT pathway, while increasing the risk of developing inflammation when expose to a HFD in female offspring liver. Testes are prone to the effect of maternal GDM, whereas ovarian metabolite profiles are upregulated in maternal GDM and downregulated in offspring following an HFD. Maternal GDM and an offspring HFD have different metabolic effects on offspring reproductive organs, and PUFAs may protect against detrimental outcomes in the offspring, such as obesity and diabetes.

Understanding Vietnam's drug policy for amphetamine-type stimulants misuse.

INTRODUCTION: The emergence of widespread amphetamine-type stimulants (ATSs) usage has created significant challenges for drug control and treatment policies in Southeast Asian countries. This study analyses the development of drug policies and examines current treatment program constraints in Vietnam to deal with ATS misuse. The aim was to gain insights that may be useful for national and international drug-related policy development and revision. METHODS: A desk review of national policy documents and 22 in-depth key informant interviews were conducted from 2019 to 2021. Thematic content analysis was employed to identify key themes and their connections. RESULTS: Analysis identified Vietnam's 30-year history of developing policies and formulating strategies to reduce supply, demand, and harm from illicit drugs. With the increasing number of people who use ATS (PWUA), Vietnam has recently promoted harsh policy and law enforcement to deter drug use and supply. This policy trend prevails in many Asian countries. The three main constraints in dealing with ATS misuse emerged from punitive and restrictive drug policies. First, the general public believed that Centre-based compulsory treatment (CCT) is the only appropriate treatment for all types of illicit drug addiction despite its low-quality service provision. The rigid drug policy has led to social persuasion with impractical expectations for CCT effectiveness. Second, the emphasis on punishment and detention has hampered new drug treatment service development in Vietnam. CCT has become monopolistic in the context of impoverished services. Third, people who use drugs tend to hide their needs and avoid formal treatment and support services, resulting in declined social coherence. CONCLUSION: While new drugs are constantly evolving, the current law enforcement approach potentially constrains expertise to adopt effective treatment services. This study suggests that the top-down policing mechanism presently hinders the development of an appropriate intervention strategy for ATS misuse and diminishes social support to service providers.

Association of infant feeding patterns with body fat mass and obesity in the first 2 years of life: a longitudinal twin birth cohort study.

Childhood obesity is a major public health problem with no effective intervention. We explored the influence of feeding patterns on infants' growth indices within the first 2 years in a twin birth cohort. Dietary intake at 12 months was recorded with a food frequency questionnaire, and dietary patterns were identified by principal component analysis. Milk feeding methods in first 6 months were categorised as breastfeeding or exclusive formula feeding. Correlations between feeding patterns and infants' growth indices were examined via generalised estimating equations. Two dietary patterns were identified and neither of which was related to growth indices. Breastfed infants had a higher body fat mass (BFM) percentage at 12 months, a higher body mass index (BMI) increment from birth to 6 months and a lower BMI increment from 6 to 12 months. Breastfed infants were likely positively correlated with BFM at 12 months; as complementary food was added, the effect of breastfeeding on growth gradually decreased.

'The second mother': How the baby food industry captures science, health professions and civil society in France.

Most babies in France are fed with infant formula and then commercial complementary foods, many of which are ultra-processed and harmful to health. Internationally, there is opposition by the baby food industry to the introduction of public health policies that would limit the marketing and consumption of such products. Our aim was to identify the key baby food industry actors, describe their history and corporate political activity (CPA) in France. We sourced publicly available information, which we triangulated with data from 10 semi-structured interviews. Qualitative thematic analysis was undertaken simultaneously to data collection, guided by an existing classification of the CPA of the food industry. The baby food industry in France has shaped the science on infant and young child nutrition and nurtured long-established relationships with health professionals. This corporate science and these relationships helped baby food companies to portray themselves as experts on child-related topics. The baby food industry has also engaged with a broad range of civil society organisations, particularly through the concept of the first 1000 days of life, and during the covid-19 pandemic. We found evidence, although limited, that the baby food industry directly lobbied the French government. Since its early development in France in the 19th century, the baby food industry used its CPA to promote its products and protect and sustain its market. Our findings can be used to recognise, anticipate and address the CPA of this industry, and to minimise any negative influence it may have on babies' and mother's health.

Potential role of FoxO3a in the regulation of trophoblast development and pregnancy complications.

The forkhead box O3a protein (FoxO3a) has been reported to regulate tumour invasion and migration, but little is known about the molecular mechanism or its role in trophoblast invasion and migration into the uterus. In this study, we aim to explore its role in trophoblast development and placenta-related pregnancy complications and the potential mechanism. Levels of FoxO3a and its phosphorylated form (p-FoxO3a) in placental tissue from healthy pregnant women and pre-eclampsia patients were first compared. Then, HTR-8/SVneo cells were transfected with lentiviral vectors to deplete and overexpress FoxO3a. Western blot, immunohistochemistry, Cell Counting Kit-8, wound-healing assay, Matrigel invasion assay, cell apoptosis, cell cycle assay, RNA sequencing, qRT-PCR and ChIP-qPCR were performed on the cells to study the potential role of FoxO3a and the underlying mechanism. We found the expression of FoxO3a was decreased, whereas p-FoxO3a was increased in pre-eclampsia placentae. FoxO3a depletion significantly reduced transcription of the promoter region of intercellular cell adhesion molecule-1 (ICAM1) gene in ChIP assays and led to reduced invasion and migration of trophoblast cells, arrested cell cycle in G1 phase and increased apoptosis under oxidative stress. Our results suggested that FoxO3a may play a role in the regulation of trophoblast invasion and migration during placental development, which may be because of its affinity to the ICAM1 promotor.

Glycerophospholipid and detoxification pathways associated with small for gestation age pathophysiology: discovery metabolomics analysis in the SCOPE cohort.

INTRODUCTION: Small for gestational age (SGA) may be associated with neonatal morbidity and mortality. Our understanding of the molecular pathways implicated is poor. OBJECTIVES: Our aim was to determine the metabolic pathways involved in the pathophysiology of SGA and examine their variation between maternal biofluid samples. METHODS: Plasma (Cork) and urine (Cork, Auckland) samples were collected at 20 weeks' gestation from nulliparous low-risk pregnant women participating in the SCOPE study. Women who delivered an SGA infant (birthweight < 10th percentile) were matched to controls (uncomplicated pregnancies). Metabolomics (urine) and lipidomics (plasma) analyses were performed using ultra performance liquid chromatography-mass spectrometry. Features were ranked based on FDR adjusted p-values from empirical Bayes analysis, and significant features putatively identified. RESULTS: Lipidomics plasma analysis revealed that 22 out of the 33 significantly altered lipids annotated were glycerophospholipids; all were detected in higher levels in SGA. Metabolomic analysis identified reduced expression of metabolites associated with detoxification (D-Glucuronic acid, Estriol-16-glucuronide), nutrient absorption and transport (Sulfolithocholic acid) pathways. CONCLUSIONS: This study suggests higher levels of glycerophospholipids, and lower levels of specific urine metabolites are implicated in the pathophysiology of SGA. Further research is needed to confirm these findings in independent samples.

Twin-twin transfusion syndrome is associated with alterations in the metabolic profile of maternal plasma in early gestation: a pilot study.

OBJECTIVE: Twin-twin transfusion syndrome (TTTS) causes perinatal mortality and morbidity in monochorionic twins. The early recognition of and interventional therapy for TTTS is associated with a more favorable overall prognosis. However, the prediction by the use of ultrasound in the first trimester has relatively poor sensitivity and specificity. This study aimed to identify metabolic biomarkers to aid in ultrasound screening of TTTS. METHODS: Maternal plasma was prospectively collected between 11 and 15 weeks of gestation in apparently uncomplicated monochorionic-diamniotic twin pregnancies. This cohort was divided into: (i) patients who were subsequently diagnosed with TTTS by using ultrasound; (ii) uncomplicated matched controls. Metabolome was profiled by using gas chromatography-mass spectrometry. RESULTS: The levels of fatty acids, organic acids, oxaloacetic acid, and beta-alanine were significantly lower in the TTTS maternal plasma at 11-15 weeks of gestation, and methionine and glycine were also higher (p < 0.05, FDR<0.12). Generally, in TTTS pregnancies, the metabolisms of amino acid, carbohydrate, cofactors, vitamins, and purine were "down-regulated"; whereas bile secretion and pyrimidine metabolism were "upregulated." CONCLUSIONS: The metabolomics scanning of early gestation maternal plasma may identify those pregnancies that subsequently develop TTTS; in particular, downregulated fatty acid levels may be biologically plausible to be implicated in the pathogenesis of TTTS.

High-flow nasal cannulae for respiratory support in adult intensive care patients.

BACKGROUND: High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adults experiencing acute respiratory failure, or at risk of acute respiratory failure, in the intensive care unit (ICU). This is an update of an earlier version of the review. OBJECTIVES: To assess the effectiveness of HFNC compared to standard oxygen therapy, or non-invasive ventilation (NIV) or non-invasive positive pressure ventilation (NIPPV), for respiratory support in adults in the ICU. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane COVID-19 Register (17 April 2020), clinical trial registers (6 April 2020) and conducted forward and backward citation searches. SELECTION CRITERIA: We included randomized controlled studies (RCTs) with a parallel-group or cross-over design comparing HFNC use versus other types of non-invasive respiratory support (standard oxygen therapy via nasal cannulae or mask; or NIV or NIPPV which included continuous positive airway pressure and bilevel positive airway pressure) in adults admitted to the ICU. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included 31 studies (22 parallel-group and nine cross-over designs) with 5136 participants; this update included 20 new studies. Twenty-one studies compared HFNC with standard oxygen therapy, and 13 compared HFNC with NIV or NIPPV; three studies included both comparisons. We found 51 ongoing studies (estimated 12,807 participants), and 19 studies awaiting classification for which we could not ascertain study eligibility information. In 18 studies, treatment was initiated after extubation. In the remaining studies, participants were not previously mechanically ventilated. HFNC versus standard oxygen therapy HFNC may lead to less treatment failure as indicated by escalation to alternative types of oxygen therapy (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.45 to 0.86; 15 studies, 3044 participants; low-certainty evidence). HFNC probably makes little or no difference in mortality when compared with standard oxygen therapy (RR 0.96, 95% CI 0.82 to 1.11; 11 studies, 2673 participants; moderate-certainty evidence). HFNC probably results in little or no difference to cases of pneumonia (RR 0.72, 95% CI 0.48 to 1.09; 4 studies, 1057 participants; moderate-certainty evidence), and we were uncertain of its effect on nasal mucosa or skin trauma (RR 3.66, 95% CI 0.43 to 31.48; 2 studies, 617 participants; very low-certainty evidence). We found low-certainty evidence that HFNC may make little or no difference to the length of ICU stay according to the type of respiratory support used (MD 0.12 days, 95% CI -0.03 to 0.27; 7 studies, 1014 participants). We are uncertain whether HFNC made any difference to the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) within 24 hours of treatment (MD 10.34 mmHg, 95% CI -17.31 to 38; 5 studies, 600 participants; very low-certainty evidence). We are uncertain whether HFNC made any difference to short-term comfort (MD 0.31, 95% CI -0.60 to 1.22; 4 studies, 662 participants, very low-certainty evidence), or to long-term comfort (MD 0.59, 95% CI -2.29 to 3.47; 2 studies, 445 participants, very low-certainty evidence). HFNC versus NIV or NIPPV We found no evidence of a difference between groups in treatment failure when HFNC were used post-extubation or without prior use of mechanical ventilation (RR 0.98, 95% CI 0.78 to 1.22; 5 studies, 1758 participants; low-certainty evidence), or in-hospital mortality (RR 0.92, 95% CI 0.64 to 1.31; 5 studies, 1758 participants; low-certainty evidence). We are very uncertain about the effect of using HFNC on incidence of pneumonia (RR 0.51, 95% CI 0.17 to 1.52; 3 studies, 1750 participants; very low-certainty evidence), and HFNC may result in little or no difference to barotrauma (RR 1.15, 95% CI 0.42 to 3.14; 1 study, 830 participants; low-certainty evidence). HFNC may make little or no difference to the length of ICU stay (MD -0.72 days, 95% CI -2.85 to 1.42; 2 studies, 246 participants; low-certainty evidence). The ratio of PaO2/FiO2 may be lower up to 24 hours with HFNC use (MD -58.10 mmHg, 95% CI -71.68 to -44.51; 3 studies, 1086 participants; low-certainty evidence). We are uncertain whether HFNC improved short-term comfort when measured using comfort scores (MD 1.33, 95% CI 0.74 to 1.92; 2 studies, 258 participants) and responses to questionnaires (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 168 participants); evidence for short-term comfort was very low certainty. No studies reported on nasal mucosa or skin trauma. AUTHORS' CONCLUSIONS: HFNC may lead to less treatment failure when compared to standard oxygen therapy, but probably makes little or no difference to treatment failure when compared to NIV or NIPPV. For most other review outcomes, we found no evidence of a difference in effect. However, the evidence was often of low or very low certainty. We found a large number of ongoing studies; including these in future updates could increase the certainty or may alter the direction of these effects.

ANTECEDENTES: Las cánulas nasales de alto flujo (HFNC) administran flujos elevados de una mezcla humedecida de aire y oxígeno a través de cánulas nasales de gran calibre y pueden ser útiles para proporcionar asistencia respiratoria a los adultos que presentan insuficiencia respiratoria aguda, o que tienen riesgo de presentarla, en la unidad de cuidados intensivos (UCI). Esta es una actualización de una versión anterior de la revisión. OBJETIVOS: Evaluar la eficacia de las HFNC en comparación con la oxigenoterapia estándar, o la ventilación no invasiva (VNI) o la ventilación con presión positiva no invasiva (VPPNI), para la asistencia respiratoria de adultos en la UCI. MÉTODOS DE BÚSQUEDA: Se realizaron búsquedas en CENTRAL, MEDLINE, Embase, CINAHL, Web of Science y en el Registro Cochrane de covid­19 (17 de abril de 2020), registros de ensayos clínicos (6 de abril de 2020) y se realizaron búsquedas de citas prospectivas y retrospectivas. CRITERIOS DE SELECCIÓN: Se incluyeron los estudios controlados aleatorizados (ECA) con un diseño de grupos paralelos o cruzados que compararon el uso de HFNC versus otro tipo de asistencia respiratoria no invasiva (oxigenoterapia estándar a través de cánulas nasales o mascarilla; o VNI o VPPNI que incluía la presión positiva continua en las vías respiratorias y la presión positiva de dos niveles en las vías respiratorias) en adultos ingresados en la UCI. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Se utilizaron los procedimientos metodológicos estándar previstos por la Colaboración Cochrane. RESULTADOS PRINCIPALES: Se incluyeron 31 estudios (22 de grupos paralelos y nueve de diseño cruzado) con 5136 participantes; esta actualización incluyó 20 estudios nuevos. Veintiún estudios compararon la HFNC con la oxigenoterapia estándar, y 13 compararon la HFNC con la VNI o la VPPNI; tres estudios incluyeron ambas comparaciones. Se encontraron 51 estudios en curso (con una estimación de 12 807 participantes) y 19 estudios en espera de clasificación en los que no fue posible determinar la información de elegibilidad del estudio. En 18 estudios el tratamiento se inició después de la extubación. En el resto de los estudios, los participantes no habían recibido de forma previa ventilación mecánica. HFNC versus oxigenoterapia estándar La HFNC podría conducir a un menor fracaso del tratamiento, según lo indicado por el escalamiento a tipos alternativos de oxigenoterapia (razón de riesgos [RR] 0,62; intervalo de confianza [IC] del 95%: 0,45 a 0,86; 15 estudios, 3044 participantes; evidencia de certeza baja). La HFNC probablemente da lugar a poca o ninguna diferencia en la mortalidad cuando se compara con la oxigenoterapia estándar (RR 0,96; IC del 95%: 0,82 a 1,11; 11 estudios, 2673 participantes; evidencia de certeza moderada). La HFNC probablemente da lugar a poca o ninguna diferencia con respecto a los casos de neumonía (RR 0,72; IC del 95%: 0,48 a 1,09; cuatro estudios, 1057 participantes; evidencia de certeza moderada), y no se sabe con certeza su efecto sobre la mucosa nasal ni el traumatismo cutáneo (RR 3,66; IC del 95%: 0,43 a 31,48; dos estudios, 617 participantes; evidencia de certeza muy baja). Se encontró evidencia de certeza baja de que la HFNC podría dar lugar a poca o ninguna diferencia en la duración de la estancia en la UCI según el tipo de asistencia respiratoria utilizada (DM 0,12 días; IC del 95%: ­0,03 a 0,27; siete estudios, 1014 participantes). No se sabe con certeza si la HFNC dio lugar a alguna diferencia en el cociente entre la presión parcial de oxígeno arterial y la fracción de oxígeno inspirado (PaO2/FiO2) en las primeras 24 horas del tratamiento (DM 10,34 mmHg; IC del 95%: ­17,31 a 38; cinco estudios, 600 participantes; evidencia de certeza muy baja). No se sabe con certeza si la HFNC dio lugar a alguna diferencia en la comodidad a corto plazo (DM 0,31; IC del 95%: ­0,60 a 1,22; cuatro estudios, 662 participantes, evidencia de certeza muy baja), o en la comodidad a largo plazo (DM 0,59; IC del 95%: ­2,29 a 3,47; dos estudios, 445 participantes, evidencia de certeza muy baja). HFNC versus VNI o VPPNI No se encontró evidencia de una diferencia entre los grupos en el fracaso del tratamiento cuando se utilizó la HFNC después de la extubación o sin el uso previo de ventilación mecánica (RR 0,98; IC del 95%: 0,78 a 1,22; cinco estudios, 1758 participantes; evidencia de certeza baja), ni en la mortalidad hospitalaria (RR 0,92; IC del 95%: 0,64 a 1,31; cinco estudios, 1758 participantes; evidencia de certeza baja). No hay certeza sobre el efecto del uso de la HFNC en la incidencia de la neumonía (RR 0,51; IC del 95%: 0,17 a 1,52; tres estudios, 1750 participantes; evidencia de certeza muy baja), y la HFNC podría dar lugar a poca o ninguna diferencia en el barotraumatismo (RR 1,15; IC del 95%: 0,42 a 3,14; un estudio, 830 participantes; evidencia de certeza baja). La HFNC podría suponer una diferencia escasa o nula en la duración de la estancia en la UCI (DM ­0,72 días; IC del 95%: ­2,85 a 1,42; dos estudios, 246 participantes; evidencia de certeza baja). El cociente PaO2/FiO2 podría ser menor hasta 24 horas con el uso de la HFNC (DM ­58,10 mmHg; IC del 95%: ­71,68 a ­44,51; tres estudios, 1086 participantes; evidencia de certeza baja). No se sabe si la HFNC mejoró la comodidad a corto plazo cuando se midió mediante puntuaciones de comodidad (DM 1,33; IC del 95%: 0,74 a 1,92; dos estudios, 258 participantes) y respuestas a cuestionarios (RR 1,30; IC del 95%: 1,10 a 1,53; un estudio, 168 participantes); la evidencia para la comodidad a corto plazo fue de certeza muy baja. Ningún estudio informó sobre la mucosa nasal ni el traumatismo cutáneo. CONCLUSIONES DE LOS AUTORES: La HFNC podría dar lugar a un menor fracaso del tratamiento en comparación con la oxigenoterapia estándar, pero probablemente suponga una escasa o nula diferencia en el fracaso del tratamiento en comparación con la VNI o la VPPNI. Para la mayoría de los demás desenlaces de la revisión, no se encontró evidencia de una diferencia en el efecto. Sin embargo, la certeza de la evidencia se consideró baja o muy baja. Se encontró un gran número de estudios en curso; incluirlos en futuras actualizaciones podría aumentar la certeza o podría alterar la dirección de estos efectos.