Apgar score and the risk of cause specific infant mortality: a population based cohort study of 1,029,207 livebirths

Background<p></p> The Apgar score has been used worldwide as an index of early neonatal condition for more than 60 years. With advances in health-care service provision, neonatal resuscitation, and infant care, its present relevance is unclear. The aim of the study was to establish the strength of the relation between Apgar score at 5 min and the risk of neonatal and infant mortality, subdivided by specific causes.<p></p> Methods<p></p> We linked routine discharge and mortality data for all births in Scotland, UK between 1992 and 2010. We restricted our analyses to singleton livebirths, in women aged over 10 years, with a gestational age at delivery between 22 and 44 weeks, and excluded deaths due to congenital anomalies or isoimmunisation. We calculated the relative risks (RRs) of neonatal and infant death of neonates with low (0–3) and intermediate (4–6) Apgar scores at 5 min referent to neonates with normal Apgar score (7–10) using binomial log-linear modelling with adjustment for confounders. Analyses were stratified by gestational age at birth because it was a significant effect modifier. Missing covariate data were imputed.<p></p> Findings<p></p> Complete data were available for 1 029 207 eligible livebirths. Across all gestational strata, low Apgar score at 5 min was associated with an increased risk of neonatal and infant death. However, the strength of the association (adjusted RR, 95% CI referent to Apgar 7–10) was strongest at term (p<0·0001). A low Apgar (0–3) was associated with an adjusted RR of 359·4 (95% CI 277·3–465·9) for early neonatal death, 30·5 (18·0–51·6) for late neonatal death, and 50·2 (42·8–59·0) for infant death. We noted similar associations of a lower magnitude for intermediate Apgar (4–6). The strongest associations were for deaths attributed to anoxia and low Apgar (0–3) for term infants (RR 961·7, 95% CI 681·3–1357·5) and preterm infants (141·7, 90·1–222·8). No association between Apgar score at 5 min and the risk of sudden infant death syndrome was noted at any gestational age (RR 0·6, 95% CI 0·1–4·6 at term; 1·2, 0·3–4·8 at preterm).<p></p> Interpretation<p></p> Low Apgar score at 5 min was strongly associated with the risk of neonatal and infant death. Our findings support its continued usefulness in contemporary practice

Five-minute Apgar score and educational outcomes: retrospective cohort study of 751 369 children

Background: The Apgar score is used worldwide for assessing the clinical condition and short-term prognosis of newborn infants. Evidence for a relationship with long-term educational outcomes is conflicting. We investigated whether Apgar score at 5 min after birth was associated with additional support needs (ASN) and educational attainment. Methods: Data on pregnancy, delivery and later educational outcomes for children attending Scottish schools between 2006 and 2011 were collated by linking individual-level data from national educational and maternity databases. The relationship between Apgar score and overall ASN, type-specific ASN and educational attainment was assessed using binary, multinomial and generalised ordinal logistic regression models, respectively. Missing covariate data were imputed. Results: Of the 751 369 children eligible, 9741 (1.3%) had a low or intermediate Apgar score and 49 962 (6.6%) had ASN. Low Apgar score was independently associated with overall ASN status (adjusted OR for Apgar ≤3, OR 1.52 95% CI 1.35 to 1.70), as well as ASN due to cognitive (OR 1.26, 95% CI 1.09 to 1.47), sensory (OR 2.49 95% CI 1.66 to 3.73) and motor (OR 3.57, 95% CI 2.86 to 4.47) impairments. There was a dose-response relationship between Apgar score and overall ASN status: of those scoring 0–3, 10.1% had ASN, compared with 9.1% of those scoring 4–7 and 6.6% of those scoring 7–10. A low Apgar score was associated with lower educational attainment, but this was not robust to adjustment for confounders. Conclusions: Apgar scores are associated with long-term as well as short-term prognoses, and with educational as well as clinical outcomes at the population level

Sleep characteristics modify the association between genetic predisposition to obesity and anthropometric measurements in 119,679 UK Biobank participants

Background - Obesity is a multifactorial condition influenced by genetics, lifestyle and environment. Objective - To investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) with body mass index (BMI) and waist circumference (WC) was modified by sleep characteristics. Design - This study included cross-sectional data from 119,859 white European adults, aged 37-73 years, participating on the UK Biobank. Interactions between GPRS-obesity, and sleep characteristics (sleep duration, chronotype, day napping, and shift work) in their effects on BMI and WC were investigated. Results - The GPRS-obesity was associated with BMI (β:0.57 kg.m-2 per standard deviation (SD) increase in GPRS, [95%CI:0.55, 0.60]; P=6.3x10-207) and WC (β:1.21 cm, [1.15, 1.28]; P=4.2x10-289). There were significant interactions between GPRS-obesity and a variety of sleep characteristics in their relationship with BMI (P-interaction <0.05). In participants who slept <7 hrs or >9 hrs daily, the effect of GPRS-obesity on BMI was stronger (β:0.60 [0.54, 0.65] and 0.73 [0.49, 0.97] kg.m-2 per SD increase in GPRS, respectively) than in normal length sleepers (7-9 hours; β:0.52 [0.49, 0.55] kg.m-2 per SD). A similar pattern was observed for shiftworkers (β:0.68 [0.59, 0.77] versus 0.54 [0.51, 0.58] kg.m-2 for non-shiftworkers) and for night-shiftworkers (β:0.69 [0.56, 0.82] versus 0.55 [0.51, 0.58] kg.m-2 for non-night- shiftworkers), for those taking naps during the day (β:0.65 [0.52, 0.78] versus 0.51 [0.48, 0.55] kg.m-2 for those who never/rarely had naps) and for those with a self-reported evening chronotype (β:0.72 [0.61, 0.82] versus β:0.52 [0.47, 0.57] kg.m-2 for morning chronotype). Similar findings were obtained using WC as the outcome. Conclusions – This study shows that the association between genetic risk for obesity and phenotypic adiposity measures is exacerbated by adverse sleeping characteristics

Impact of Scotland's smoke-free legislation on pregnancy complications: retrospective cohort study

BACKGROUND Both active smoking and environmental tobacco smoke exposure are associated with pregnancy complications. In March 2006, Scotland implemented legislation prohibiting smoking in all wholly or partially enclosed public spaces. The aim of this study was to determine the impact of this legislation on preterm delivery and small for gestational age. METHODS AND FINDINGS We conducted logistic regression analyses using national administrative pregnancy data covering the whole of Scotland. Of the two breakpoints tested, 1 January 2006 produced a better fit than the date when the legislation came into force (26 March 2006), suggesting an anticipatory effect. Among the 716,941 eligible women who conceived between August 1995 and February 2009 and subsequently delivered a live-born, singleton infant between 24 and 44 wk gestation, the prevalence of current smoking fell from 25.4% before legislation to 18.8% after legislation (p<0.001). Three months prior to the legislation, there were significant decreases in small for gestational age (-4.52%, 95% CI -8.28, -0.60, p = 0.024), overall preterm delivery (-11.72%, 95% CI -15.87, -7.35, p<0.001), and spontaneous preterm labour (-11.35%, 95% CI -17.20, -5.09, p = 0.001). In sub-group analyses, significant reductions were observed among both current and never smokers. CONCLUSIONS Reductions were observed in the risk of preterm delivery and small for gestational age 3 mo prior to the introduction of legislation, although the former reversed partially following the legislation. There is growing evidence of the potential for tobacco control legislation to have a positive impact on health

Alzheimer disease genetic risk factor APOE e4, and cognitive abilities in 111,739 UK Biobank participants

Background: the apolipoprotein (APOE) e4 locus is a genetic risk factor for dementia. Carriers of the e4 allele may be more vulnerable to conditions that are independent risk factors for cognitive decline, such as cardiometabolic diseases. Objective: we tested whether any association with APOE e4 status on cognitive ability was larger in older ages or in those with cardiometabolic diseases. Subjects: UK Biobank includes over 500,000 middle- and older aged adults who have undergone detailed medical and cognitive phenotypic assessment. Around 150,000 currently have genetic data. We examined 111,739 participants with complete genetic and cognitive data. Methods: baseline cognitive data relating to information processing speed, memory and reasoning were used. We tested for interactions with age and with the presence versus absence of type 2 diabetes (T2D), coronary artery disease (CAD) and hypertension. Results: in several instances, APOE e4 dosage interacted with older age and disease presence to affect cognitive scores. When adjusted for potentially confounding variables, there was no APOE e4 effect on the outcome variables. Conclusions: future research in large independent cohorts should continue to investigate this important question, which has potential implications for aetiology related to dementia and cognitive impairment

The impact of confounding on the associations of different adiposity measures with the incidence of cardiovascular disease: a cohort study of 296 535 adults of white European descent

Aims: The data regarding the associations of body mass index (BMI) with cardiovascular (CVD) risk, especially for those at the low categories of BMI, are conflicting. The aim of our study was to examine the associations of body composition (assessed by five different measures) with incident CVD outcomes in healthy individuals. Methods and results: A total of 296 535 participants (57.8% women) of white European descent without CVD at baseline from the UK biobank were included. Exposures were five different measures of adiposity. Fatal and non-fatal CVD events were the primary outcome. Low BMI (≤18.5 kg m−2) was associated with higher incidence of CVD and the lowest CVD risk was exhibited at BMI of 22–23 kg m−2 beyond, which the risk of CVD increased. This J-shaped association attenuated substantially in subgroup analyses, when we excluded participants with comorbidities. In contrast, the associations for the remaining adiposity measures were more linear; 1 SD increase in waist circumference was associated with a hazard ratio of 1.16 [95% confidence interval (CI) 1.13–1.19] for women and 1.10 (95% CI 1.08–1.13) for men with similar magnitude of associations for 1 SD increase in waist-to-hip ratio, waist-to-height ratio, and percentage body fat mass. Conclusion: Increasing adiposity has a detrimental association with CVD health in middle-aged men and women. The association of BMI with CVD appears more susceptible to confounding due to pre-existing comorbidities when compared with other adiposity measures. Any public misconception of a potential ‘protective’ effect of fat on CVD risk should be challenged

Association between active commuting and incident cardiovascular disease, cancer, and mortality: prospective cohort study

Objective: To investigate the association between active commuting and incident cardiovascular disease (CVD), cancer, and all cause mortality. Design: Prospective population based study. Setting: UK Biobank. Participants: 263 450 participants (106 674 (52%) women; mean age 52.6), recruited from 22 sites across the UK. The exposure variable was the mode of transport used (walking, cycling, mixed mode v non-active (car or public transport)) to commute to and from work on a typical day. Main outcome measures: Incident (fatal and non-fatal) CVD and cancer, and deaths from CVD, cancer, or any causes. Results: 2430 participants died (496 were related to CVD and 1126 to cancer) over a median of 5.0 years (interquartile range 4.3-5.5) follow-up. There were 3748 cancer and 1110 CVD events. In maximally adjusted models, commuting by cycle and by mixed mode including cycling were associated with lower risk of all cause mortality (cycling hazard ratio 0.59, 95% confidence interval 0.42 to 0.83, P=0.002; mixed mode cycling 0.76, 0.58 to 1.00, P<0.05), cancer incidence (cycling 0.55, 0.44 to 0.69, P<0.001; mixed mode cycling 0.64, 0.45 to 0.91, P=0.01), and cancer mortality (cycling 0.60, 0.40 to 0.90, P=0.01; mixed mode cycling 0.68, 0.57 to 0.81, P<0.001). Commuting by cycling and walking were associated with a lower risk of CVD incidence (cycling 0.54, 0.33 to 0.88, P=0.01; walking 0.73, 0.54 to 0.99, P=0.04) and CVD mortality (cycling 0.48, 0.25 to 0.92, P=0.03; walking 0.64, 0.45 to 0.91, P=0.01). No statistically significant associations were observed for walking commuting and all cause mortality or cancer outcomes. Mixed mode commuting including walking was not noticeably associated with any of the measured outcomes. Conclusions: Cycle commuting was associated with a lower risk of CVD, cancer, and all cause mortality. Walking commuting was associated with a lower risk of CVD independent of major measured confounding factors. Initiatives to encourage and support active commuting could reduce risk of death and the burden of important chronic conditions

Low birth weight and features of neuroticism and mood disorder in 83 545 participants of the UK Biobank cohort

Background: Low birth weight has been inconsistently associated with risk of developing affective disorders, including major depressive disorder (MDD). To date, studies investigating possible associations between birth weight and bipolar disorder (BD), or personality traits known to predispose to affective disorders such as neuroticism, have not been conducted in large cohorts.Aims: To assess whether very low birth weight (<1500 g) and low birth weight (1500–2490 g) were associated with higher neuroticism scores assessed in middle age, and lifetime history of either MDD or BD. We controlled for possible confounding factors.Method: Retrospective cohort study using baseline data on the 83?545 UK Biobank participants with detailed mental health and birth weight data. Main outcomes were prevalent MDD and BD, and neuroticism assessed using the Eysenck Personality Inventory Neuroticism scale - Revised (EPIN-R)Results: Referent to normal birth weight, very low/low birth weight were associated with higher neuroticism scores, increased MDD and BD. The associations between birth weight category and MDD were partially mediated by higher neuroticism.Conclusions: These findings suggest that intrauterine programming may play a role in lifetime vulnerability to affective disorders

Thioredoxins function as deglutathionylase enzymes in the yeast Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>Protein-SH groups are amongst the most easily oxidized residues in proteins, but irreversible oxidation can be prevented by protein glutathionylation, in which protein-SH groups form mixed disulphides with glutathione. Glutaredoxins and thioredoxins are key oxidoreductases which have been implicated in regulating glutathionylation/deglutathionylation in diverse organisms. Glutaredoxins have been proposed to be the predominant deglutathionylase enzymes in many plant and mammalian species, whereas, thioredoxins have generally been thought to be relatively inefficient in deglutathionylation.</p> <p>Results</p> <p>We show here that the levels of glutathionylated proteins in yeast are regulated in parallel with the growth cycle, and are maximal during stationary phase growth. This increase in glutathionylation is not a response to increased reactive oxygen species generated from the shift to respiratory metabolism, but appears to be a general response to starvation conditions. Our data indicate that glutathionylation levels are constitutively high in all growth phases in thioredoxin mutants and are unaffected in glutaredoxin mutants. We have confirmed that thioredoxins, but not glutaredoxins, catalyse deglutathionylation of model glutathionylated substrates using purified thioredoxin and glutaredoxin proteins. Furthermore, we show that the deglutathionylase activity of thioredoxins is required to reduce the high levels of glutathionylation in stationary phase cells, which occurs as cells exit stationary phase and resume vegetative growth.</p> <p>Conclusions</p> <p>There is increasing evidence that the thioredoxin and glutathione redox systems have overlapping functions and these present data indicate that the thioredoxin system plays a key role in regulating the modification of proteins by the glutathione system.</p