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.

Investigating the beliefs of Saudi females regarding physical activity: a qualitative exploration.

PURPOSE: Saudi women have been deprived of equal access to and opportunities for an active lifestyle due to sociocultural restrictions. Using the theory of planned behaviour, this elicitation study aimed to explore the salient beliefs of young Saudi women aged 18-35 regarding physical activity (PA). METHODS: A descriptive qualitative methodology was utilized using a semi-structured interview. A total of 25 transcribed interviews were coded. Content analysis was used to identify the salient beliefs and to rank-order the beliefs using an adaptation of Burnard's model. FINDINGS: Thirty-five salient beliefs were identified as dominant factors in the decision to engage in PA. The salient beliefs about PA are classified as positive (related to advantages, social approval, and enabling) and negative (related to disadvantages, social disapproval, and barriers). These included behavioural beliefs (concerning physical/psychological well-being and social opportunities), normative beliefs (concerning family, community, international and local media influencers' expectations), and control beliefs (concerning personal, social, natural, and built environment enablers as well as constraints). CONCLUSIONS: Due to the elicited beliefs, young women may be able to adopt more active lifestyles and change their inactive behaviour. Addressing negative beliefs can help change their inactive behaviour. Strengthening positive beliefs and facilitators is also beneficial.

Positive and negative emotions during the COVID-19 pandemic: A longitudinal survey study of the UK population.

The COVID-19 pandemic has had a profound impact on society; it changed the way we work, learn, socialise, and move throughout the world. In the United Kingdom, policies such as business closures, travel restrictions, and social distance mandates were implemented to slow the spread of COVID-19 and implemented and relaxed intermittently throughout the response period. While negative emotions and feelings such as distress and anxiety during this time of crisis were to be expected, we also see the signs of human resilience, including positive feelings like determination, pride, and strength. A longitudinal study using online survey tools was conducted to assess people's changing moods during the pandemic in the UK. The Positive and Negative Affect Schedule (PANAS) was used to measure self-reported feelings and emotions throughout six periods (phases) of the study from March 2020 to July 2021. A total of 4,222 respondents participated in the survey, while a sub-group participated in each of the six study phases (n = 167). The results were analysed using a cross-sectional study design for the full group across each study phase, while prospective cohort analysis was used to assess the subset of participants who voluntarily answered the survey in each of the six study phases (n = 167). Gender, age and employment status were found to be most significant to PANAS score, with older people, retirees, and women generally reporting more positive moods, while young people and unemployed people generally reported lower positive scores and higher negative scores, indicating more negative emotions. Additionally, it was found that people generally reported higher positive feelings in the summer of 2021, which may be related to the relaxation of COVID-19-related policies in the UK as well as the introduction of vaccines for the general population. This study is an important investigation into what allows for positivity during a crisis and gives insights into periods or groups that may be vulnerable to increased negative states of emotions and feelings.

Ultraprocessing and presence of additives in commercially produced complementary foods in seven Southeast Asian countries: a cross-sectional study.

BACKGROUND: There has been a dramatic shift in food systems, and the consumption of commercially processed and packaged foods has grown globally, including among older infants and young children. Many of these products are ultraprocessed and contain additives, with concerning implications for the health and nutrition of children. OBJECTIVES: The study objectives were as follows: 1) to assess the levels of processing among different commercially produced complementary food product (CPCF) categories marketed in the Southeast Asia region, 2) to compare the nutrient content of CPCF products across levels of processing, and 3) to assess the types of additives present in different CPCF categories. METHODS: This cross-sectional study involved secondary analysis of a cross-sectional dataset of product label information from CPCF purchased in 2021 in Cambodia, Indonesia, Lao People's Democratic Republic, Malaysia, Philippines, Thailand, and Viet Nam. Ingredient lists were reviewed to determine the level of processing-based on the Nova classification-and the presence of additives. Nutrient declaration panels were reviewed to determine total sugar, sodium, and total fat. RESULTS: Nearly half of all CPCF were ultraprocessed, with total sugar and sodium content significantly higher among ultraprocessed CPCF than unprocessed/minimally processed products. Almost half of CPCF contained additives, with a median of 6 per product. More than 30% of all CPCF made use of cosmetic additives to enhance the products' appearance, flavor, or texture, with emulsifiers, colors, and thickeners the most prevalent. Almost one-third of products contained additives not permitted in Codex Alimentarius standards and guidelines for CPCF. CONCLUSIONS: Findings from this study should alert national governments to both adopt and ensure enforcement of Codex guidance on additives and regulations enacted to encourage lower levels of processing for CPCF.

Associations of air pollution exposures in preconception and pregnancy with birth outcomes and infant neurocognitive development: analysis of the Complex Lipids in Mothers and Babies (CLIMB) prospective cohort in Chongqing, China.

OBJECTIVES: To investigate the associations of traffic-related air pollution exposures in early pregnancy with birth outcomes and infant neurocognitive development. DESIGN: Cohort study. SETTING: Eligible women attended six visits in the maternity clinics of two centres, the First Affiliated Hospital of Chongqing Medical University and Chongqing Health Centre for Women and Children. PARTICIPANTS: Women who were between 20 and 40 years of age and were at 11-14 weeks gestation with a singleton pregnancy were eligible for participation. Women were excluded if they had a history of premature delivery before 32 weeks of gestation, maternal milk allergy or aversion or severe lactose intolerance. 1273 pregnant women enrolled in 2015-2016 and 1174 live births were included in this analysis. EXPOSURES: Air pollution concentrations at their home addresses, including particulate matter with diameter ≤2.5 µm (PM2.5) and nitrogen dioxide (NO2), during pre-conception and each trimester period were estimated using land-use regression models. OUTCOME MEASURES: Birth outcomes (ie, birth weight, birth length, preterm birth, low birth weight, large for gestational age and small for gestational age (SGA) status) and neurodevelopment outcomes measured by the Chinese version of Bayley Scales of Infant Development. RESULTS: An association between SGA and per-IQR increases in NO2 was found in the first trimester (OR: 1.57, 95% CI: 1.06 to 2.32) and during the whole pregnancy (OR: 1.33, 99% CI: 1.01 to 1.75). Both PM2.5 and NO2 exposure in the 90 days prior to conception were associated with lower Psychomotor Development Index scores (ß: -6.15, 95% CI: -8.84 to -3.46; ß: -2.83, 95% CI: -4.27 to -1.39, respectively). Increased NO2 exposure was associated with an increased risk of psychomotor development delay during different trimesters of pregnancy. CONCLUSIONS: Increased exposures to NO2 during pregnancy were associated with increased risks of SGA and psychomotor development delay, while increased exposures to both PM2.5 and NO2 pre-conception were associated with adverse psychomotor development outcomes at 12 months of age. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16007700.

The attenuation of gut microbiota-derived short-chain fatty acids elevates lipid transportation through suppression of the intestinal HDAC3-H3K27ac-PPAR-γ axis in gestational diabetes mellitus.

Gut flora is considered to modulate lipid transport from the intestine into the bloodstream, and thus may potentially participate in the development of GDM. Although previous studies have shown that the intestinal microbiota influences lipid transport and metabolism in GDM, the precise mechanisms remain elusive. To address this, we used a high-fat diet (HFD)-induced GDM mouse model and conducted 16s rRNA sequencing and fecal metabolomics to assess gut microbial community shifts and associated metabolite changes. Western blot, ELISA, and chromatin immunoprecipitation (ChIP) were utilized to elucidate how gut microbiota affect intestinal lipid transport and the insulin sensitivity of hepatic, adipose, and skeletal muscle tissues. We found that HFD impaired the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) in pregnant mice. 16s rRNA sequencing demonstrated profound compositional changes, especially in the relative abundances of Firmicutes and Bacteroidetes. Metabolomics analysis presented a decline in the concentration of short-chain fatty acids (SCFAs) in the GDM group. Western blot analyses showed an upregulation of HDAC3 and a concurrent reduction in H3K27 acetylation in the intestine. ChIP-qPCR showed that PPAR-γ was inhibited, which in turn activated lipid-transporter CD36. ELISA and insulin signaling pathway detection in insulin-target organs showed high concentrations of circulating fatty acids and triglycerides and insulin resistance in insulin-target organs. Our results suggest that gut microbiota is closely associated with the development of GDM, partly because decreased gut flora-associated SCFAs activate CD36 by suppressing the HDAC3-H3K27ac-PPAR-γ axis to transport excessive fatty acids and triglycerides into blood circulation, thereby dysregulating the insulin sensitivity of insulin target organs.

Evidence for ethnicity and location as regulators of the newborn blood metabolome: a monozygous twin study.

Introduction: Monochorionic, diamniotic (MCDA) monozygotic twins share nearly all genetic variation and a common placenta in utero. Despite this, MCDA twins are often discordant for a range of common phenotypes, including early growth and birth weight. As such, MCDA twins represent a unique model to explore variation in early growth attributable primarily to in utero environmental factors. Methods: MCDA twins with a range of within-pair birth weight discordance were sampled from the peri/postnatal epigenetic twin study (PETS, Melbourne; n = 26 pairs), Beijing twin study (BTS, Beijing; n = 25), and the Chongqing longitudinal twin study (LoTiS, Chongqing; n = 22). All PETS participants were of European-Australian ancestry, while all Chinese participants had Han ancestry. The average of the birth weight difference between the larger and smaller co-twins for all twin pairs was determined and metabolomic profiles of amino acids, TCA cycle intermediates, fatty acids, organic acids, and their derivatives generated from cord blood plasma by gas chromatograph mass spectrometry. Within and between co-twin pair analyses were performed to identify metabolites specifically associated with discordance in birth weight. Multivariable regression and pathway enrichment analyses between different regions were performed to evaluate the geographical effects on the metabolism of MCDA twin pairs. Results: PETS twins showed a markedly different metabolic profile at birth compared to the two Chinese samples. Within-pair analysis revealed an association of glutathione, creatinine, and levulinic acid with birth weight discordance. Caffeine, phenylalanine, and several saturated fatty acid levels were uniquely elevated in PETS twins and were associated with maternal BMI and average within pair birth weight, in addition to birth weight discordance. LoTiS twins had higher levels of glutathione, tyrosine, and gamma-linolenic acid relative to PETS and BTS twins, potentially associated with eating habits. Conclusion: This study highlights the potential role of underlying genetic variation (shared by MZ twins), in utero (non-shared by MZ twins) and location-specific (shared by MZ twins) environmental factors, in regulating the cord blood metabolome of uncomplicated MCDA twins. Future research is needed to unravel these complex relationships that may play a key role in phenotypic metabolic alterations of twins independent of genetic diversity.

Cohort profile: Improved Pregnancy Outcomes via Early Detection (IMPROvED), an International Multicentre Prospective Cohort.

Background: Improved Pregnancy Outcomes via Early Detection (IMPROvED) is a multi-centre, European phase IIa clinical study. The primary aim of IMPROvED is to enable the assessment and refinement of innovative prototype preeclampsia risk assessment tests based on emerging biomarker technologies. Here we describe IMPROvED's profile and invite researchers to collaborate. Methods: A total of 4,038 low-risk nulliparous singleton pregnancies were recruited from maternity units in Ireland (N=1,501), United Kingdom (N=1,108), The Netherlands (N=810), and Sweden (N=619) between November 2013 to August 2017. Participants were interviewed by a research midwife at ~11 weeks (optional visit), ~15 weeks, ~20 weeks, ~34 weeks' gestation (optional visit), and postpartum (within 72-hours following delivery). Findings to date: Clinical data included information on maternal sociodemographic, medical history, and lifestyle factors collected at ~15 weeks' gestation, and maternal measurements, collected at each study visit. Biobank samples included blood, urine, and hair collected at each study visit throughout pregnancy in all units plus umbilical cord/blood samples collected at birth in Ireland and Sweden. A total of 74.0% (N=2,922) had an uncomplicated pregnancy, 3.1% (N=122) developed preeclampsia, 3.6% (N=143) had a spontaneous preterm birth, and 10.5% (N=416) had a small for gestational age baby. We evaluated a panel of metabolite biomarkers and a panel of protein biomarkers at 15 weeks and 20 weeks' gestation for preeclampsia risk assessment. Their translation into tests with clinical application, as conducted by commercial entities, was hampered by technical issues and changes in test requirements. Work on the panel of proteins was abandoned, while work on the use of metabolite biomarkers for preeclampsia risk assessment is ongoing. Future plans: In accordance with the original goals of the IMPROvED study, the data and biobank are now available for international collaboration to conduct high quality research into the cause and prevention of adverse pregnancy outcomes.