Lifestyle factors, adiposity and cardiometabolic risk factors in South Asian women living in Scotland

South Asians migrating to the Western world have a 3 to 5-fold higher risk of developing type 2 diabetes and double the risk of cardiovascular disease (CVD) than the background population of White European descent, without exhibiting a proportional higher prevalence of conventional cardiometabolic risk factors. Notably, women of South Asian descent are more likely to be diagnosed with type 2 diabetes as they grow older compared with South Asian men and, in addition, they have lost the cardio-protective effects of being females. Despite South Asian women in Western countries being a high risk group for developing future type 2 diabetes and CVD, they have been largely overlooked. The aims of this thesis were to compare lifestyle factors, body composition and cardiometabolic risk factors in healthy South Asian and European women who reside in Scotland, to examine whether ethnicity modifies the associations between modifiable environmental factors and cardiometabolic risks and to assess whether vascular reactivity is altered by ethnicity or other conventional and novel CVD risks. I conducted a cross-sectional study and recruited 92 women of South Asian and 87 women of White European descent without diagnosed diabetes or CVD. Women on hormone replacement therapy or hormonal contraceptives were excluded too. Age and body mass index (BMI) did not differ between the two ethnic groups. Physical activity was assessed and with self-reported questionnaires and objectively with the use of accelerometers. Cardiorespiratory fitness was quantified with the predicted maximal oxygen uptake (VO2 max) during a submaximal test (Chester step test). Body composition was assessed with skinfolds measured at seven body sites, five body circumferences, measurement of abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) with the use of magnetic resonance imaging (MRI) and liver fat with the use MR spectroscopy. Dietary density was assessed with food frequency questionnaires. Vascular response was assessed by measuring the response to acetylcholine and sodium nitroprusside with the use of Laser Doppler Imaging with Iontophoresis (LDI-ION) and the response to shear stress with the use of Peripheral Arterial Tonometry (EndoPAT). The South Asian women exhibited a metabolic profile consistent with the insulin resistant phenotype, characterised by greater levels of fasting insulin, lower levels of high density lipoprotein (HDL) and higher levels of triglycerides (TG) compared with their European counterparts. In addition, the South Asians had greater levels of glycated haemoglobin (HbA1c) for any given level of fasting glucose. The South Asian women engaged less time weekly with moderate to vigorous physical activity (MVPA) and had lower levels of cardiorespiratory fitness for any given level of physical activity than the women of White descent. In addition, they accumulated more fat centrally for any given BMI. Notably, the South Asians had equivalent SAT with the European women but greater VAT and hepatic fat for any given BMI. Dietary density did not differ among the groups. Increasing central adiposity had the largest effect on insulin resistance in both ethic groups compared with physical inactivity or decreased cardiorespiratory fitness. Interestingly, ethnicity modified the association between central adiposity and insulin resistance index with a similar increase in central adiposity having a substantially larger effect on insulin resistance index in the South Asian women than in the Europeans. I subsequently examined whether ethnic specific thresholds are required for lifestyle modifications and demonstrated that South Asian women need to engage with MVPA for around 195 min.week-1 in order to equate their cardiometabolic risk with that of the Europeans exercising 150 min.week-1. In addition, lower thresholds of abdominal adiposity and BMI should apply for the South Asians compared with the conventional thresholds. Although the South Asians displayed an adverse metabolic profile, vascular reactivity measured with both methods did not differ among the two groups. An additional finding was that menopausal women with hot flushing of both ethnic groups showed a paradoxical vascular profile with enhanced skin perfusion (measured with LDI-ION) but decreased reactive hyperaemia index (measured with EndoPAT) compared with asymptomatic menopausal women. The latter association was independent of conventional CVD risk factors. To conclude, South Asian women without overt disease who live in Scotland display an adverse metabolic profile with steeper associations between lifestyle risk factors and adverse cardiometabolic outcomes compared with their White counterparts. Further work in exploring ethnic specific thresholds in lifestyle interventions or in disease diagnosis is warranted

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

Machine learning and disease prediction in obstetrics

Machine learning technologies and translation of artificial intelligence tools to enhance the patient experience are changing obstetric and maternity care. An increasing number of predictive tools have been developed with data sourced from electronic health records, diagnostic imaging and digital devices. In this review, we explore the latest tools of machine learning, the algorithms to establish prediction models and the challenges to assess fetal well-being, predict and diagnose obstetric diseases such as gestational diabetes, pre-eclampsia, preterm birth and fetal growth restriction. We discuss the rapid growth of machine learning approaches and intelligent tools for automated diagnostic imaging of fetal anomalies and to asses fetoplacental and cervix function using ultrasound and magnetic resonance imaging. In prenatal diagnosis, we discuss intelligent tools for magnetic resonance imaging sequencing of the fetus, placenta and cervix to reduce the risk of preterm birth. Finally, the use of machine learning to improve safety standards in intrapartum care and early detection of complications will be discussed. The demand for technologies to enhance diagnosis and treatment in obstetrics and maternity should improve frameworks for patient safety and enhance clinical practice

Excessive age-related decline in functional ovarian reserve in infertile women: prospective cohort of 15,500 women

Context: Whether infertile women exhibit accelerated ovarian aging and whether a low ovarian reserve is overrepresented in infertility populations is not known. Objective: To compare the age-related decline in antral follicle count (AFC), a biomarker of the ovarian reserve, in fertile and infertile women. Design: Cross-sectional data from a large prospective cohort study conducted from January 2013 to December 2014. Setting: Thirteen fertility centers across Spain. Patients or Other Participants: Consecutive women aged 18 to 45 years of age attending the fertility centers either seeking fertility treatment or as fertile women wishing to act as potential oocyte donors. Intervention(s): Standardized AFC assessment on day 2 to 4 of the cycle. Main Outcome Measure(s): Age-related decline of AFC for both fertile and infertile women. Results: A total of 15 500 women, of whom 5722 were potential donors and 9778 were patients seeking fertility treatment, participated in the study. Average AFC was greater in potential oocyte donors than in infertile women (20 [interquartile range, 16–24] vs 10 [interquartile range, 6–15], respectively; P < .001), a difference that was maintained after adjustment for age (P < .001) in a model predicting log(AFC) from donor vs infertility, adjusting for 2-year age bands. The age-related decline in AFC was much steeper in infertile women compared with that of potential oocyte donors, with an increased prevalence of a low ovarian reserve (AFC < 5) at all ages in infertile women. Conclusions: The age-related decline in AFC was substantially greater in infertility patients than potential oocyte donors. Overrepresentation in infertility populations of women with low ovarian reserve may be an additional functional cause of infertility

Prediction of ovarian response using the automated Elecsys anti-Müllerian hormone assay in gonadotrophin-releasing hormone antagonist cycles

Research question: What is the capability of serum anti-Müllerian hormone (AMH) measured using the automated Elecsys® AMH immunoassay to (Roche Diagnostics International Ltd) determine ovarian response after fertility treatment? Design: Single-centre, retrospective, observational, cohort study including women undergoing ovarian stimulation. Serum AMH concentrations were determined using the Elecsys AMH immunoassay based on one blood sample drawn 6 months or less before treatment. Stimulation was conducted in accordance with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Patients were divided into four ovarian response categories based on their oocyte yield: low (0–3), suboptimal (4–9), optimal (10–15) and high (>15). Areas under the curve were calculated for each ovarian response group. Results: Overall, 1248 patients were enrolled. The AMH concentration had a strong positive correlation with oocyte yield (Spearman's rho = 0.74, P < 0.001). Areas under the curve (95% CI) for AMH predicting ovarian response were 0.85 (0.83 to 0.88) for low and 0.89 (0.87 to 0.91) for high response. Optimal serum AMH cut-offs for predicting a low and high response using the Elecsys AMH immunoassay were 6.4 pmol/l (0.89 ng/ml) and 14.2 pmol/l (1.99 ng/ml), respectively. Multivariable regression analysis showed that 47% (R2 = 0.470) of variation in ovarian response could be attributed to AMH alone, increasing to 50.9% (R2 = 0.509) with the addition of age, body weight, and total dose of gonadotrophin. Conclusion: Ovarian response and oocyte yield after stimulation in a GnRH antagonist cycle can be predicted with high accuracy using a single determination of serum AMH before ovarian stimulation

Impact of GnRH agonist triggering and intensive luteal steroid support on live-birth rates and ovarian hyperstimulation syndrome:a retrospective cohort study

BACKGROUND: Conventional luteal support packages are inadequate to facilitate a fresh transfer after GnRH agonist (GnRHa) trigger in patients at high risk of developing ovarian hyperstimulation syndrome (OHSS). By providing intensive luteal-phase support with oestradiol and progesterone satisfactory implantation rates can be sustained. The objective of this study was to assess the live-birth rate and incidence of OHSS after GnRHa trigger and intensive luteal steroid support compared to traditional hCG trigger and conventional luteal support in OHSS high risk Asian patients. METHODS: We conducted a retrospective cohort study of 363 women exposed to GnRHa triggering with intensive luteal support compared with 257 women exposed to conventional hCG triggering. Women at risk of OHSS were defined by ovarian response ≥15 follicles ≥12 mm on the day of the trigger. RESULTS: Live-birth rates were similar in both groups GnRHa vs hCG; 29.8% vs 29.2% (p = 0.69). One late onset severe OHSS case was observed in the GnRHa trigger group (0.3%) compared to 18 cases (7%) after hCG trigger. CONCLUSIONS: GnRHa trigger combined with intensive luteal steroid support in this group of OHSS high risk Asian patients can facilitate fresh embryo transfer, however, in contrast to previous reports the occurrence of late onset OHSS was not completely eliminated

Age at menarche and cardiometabolic health::a sibling analysis in the Scottish Family Health Study

Background: Previous studies of age at menarche and cardiometabolic health report conflicting findings, and only a few could account for childhood characteristics. We aimed to estimate the associations of age at menarche with cardiovascular risk factors in unrelated women and within sister groups, under the assumption that within‐sibship estimates will be better adjusted for shared genetics and early life environment. Methods and Results: Our study included 7770 women, from 5984 sibships, participating in the GS:SFHS (Generation Scotland: Scottish Family Health Study). We used fixed‐ and between‐effects linear regression to estimate the associations within sister groups and between unrelated individuals, respectively. Within sibships, the mean difference between sisters with early menarche (≤11 years) and sisters with menarche at 12 to 13 years was 1.73 mm Hg (95% confidence interval [CI], −0.41 to 3.86) for systolic blood pressure, 1.26 mm Hg (95% CI, −0.02 to 2.55) for diastolic blood pressure, −0.06 nmol/L (95% CI, −0.11 to −0.02) for high‐density lipoprotein, 0.20 nmol/L (95% CI, 0.08–0.32) for non–high‐density lipoprotein, −0.34% (95% CI, −1.98 to 1.30) for glucose, 1.60 kg/m2 (95% CI, 0.92–2.28) for body mass index, and 2.75 cm (95% CI, 1.06–4.44) for waist circumference. There was weak evidence of associations between later menarche (14–15 or ≥16 years) and lower body mass index, waist circumference, and blood pressure. We found no strong evidence that estimates from within‐ and between‐sibship analyses differed (all P values >0.1). The associations with other cardiovascular risk factors were attenuated after adjustment for adult body mass index. Conclusions: Our results suggest that confounding by shared familial characteristics is unlikely to be a major driver of the association between early menarche and adverse cardiometabolic health but do not exclude confounding by individual‐level characteristics

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

Customised and Noncustomised Birth Weight Centiles and Prediction of Stillbirth and Infant Mortality and Morbidity: A Cohort Study of 979,912 Term Singleton Pregnancies in Scotland.

BACKGROUND: There is limited evidence to support the use of customised centile charts to identify those at risk of stillbirth and infant death at term. We sought to determine birth weight thresholds at which mortality and morbidity increased and the predictive ability of noncustomised (accounting for gestational age and sex) and partially customised centiles (additionally accounting for maternal height and parity) to identify fetuses at risk. METHODS: This is a population-based linkage study of 979,912 term singleton pregnancies in Scotland, United Kingdom, between 1992 and 2010. The main exposures were noncustomised and partially customised birth weight centiles. The primary outcomes were infant death, stillbirth, overall mortality (infant and stillbirth), Apgar score <7 at 5 min, and admission to the neonatal unit. Optimal thresholds that predicted outcomes for both non- and partially customised birth weight centiles were calculated. Prediction of mortality between non- and partially customised birth weight centiles was compared using area under the receiver operator characteristic curve (AUROC) and net reclassification index (NRI). FINDINGS: Birth weight ≤25th centile was associated with higher risk for all mortality and morbidity outcomes. For stillbirth, low Apgar score, and neonatal unit admission, risk also increased from the 85th centile. Similar patterns and magnitude of associations were observed for both non- and partially customised birth weight centiles. Partially customised birth weight centiles did not improve the discrimination of mortality (AUROC 0.61 [95%CI 0.60, 0.62]) compared with noncustomised birth weight centiles (AUROC 0.62 [95%CI 0.60, 0.63]) and slightly underperformed in reclassifying pregnancies to different risk categories for both fatal and non-fatal adverse outcomes (NRI -0.027 [95% CI -0.039, -0.016], p < 0.001). We were unable to fully customise centile charts because we lacked data on maternal weight and ethnicity. Additional analyses in an independent UK cohort (n = 10,515) suggested that lack of data on ethnicity in this population (in which national statistics show 98% are white British) and maternal weight would have misclassified ~15% of the large-for-gestation fetuses. CONCLUSIONS: At term, birth weight remains strongly associated with the risk of stillbirth and infant death and neonatal morbidity. Partial customisation does not improve prediction performance. Consideration of early term delivery or closer surveillance for those with a predicted birth weight ≤25th or ≥85th centile may reduce adverse outcomes. Replication of the analysis with fully customised centiles accounting for ethnicity is warranted.SI is funded by a UK Medical Research Council skills development fellowship (MR/N015177/1). DAL works in a Unit that receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_12013/5); she is a National Institute of Health Research (NIHR) Senior Investigator (NF-SI-0611-10196). This work is also supported by the NIHR through the University of Bristol NIHR Biomedical Research Centre (BRC) and the University of Cambridge BRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants

Background: Obesity is a multifactorial condition influenced by both genetics and lifestyle. The aim of this study was to investigate whether the association between a validated genetic profile risk score for obesity (GPRS-obesity) and body mass index (BMI) or waist circumference (WC) was modified by macronutrient intake in a large general population study. Methods: This study included cross-sectional data from 48 170 white European adults, aged 37–73 years, participating on the UK Biobank. Interactions between GPRS-obesity, and macronutrient intake (including total energy, protein, fat, carbohydrate and dietary fibre intake) and its effects on BMI and WC were investigated. Results: The 93-SNPs genetic profile risk score was associated with a higher BMI (β:0.57 kg.m−2 per standard deviation (s.d.) increase in GPRS, [95%CI:0.53–0.60]; P=1.9 × 10−183) independent of major confounding factors. There was a significant interaction between GPRS and total fat intake (P[interaction]=0.007). Among high fat intake individuals, BMI was higher by 0.60 [0.52, 0.67] kg.m−2 per s.d. increase in GPRS-obesity; the change in BMI with GPRS was lower among low fat intake individuals (β:0.50 [0.44, 0.57] kg.m-2). Significant interactions with similar patterns were observed for saturated fat intake (High β:0.66 [0.59, 0.73] versus Low β:0.49 [0.42, 0.55] kg.m-2, P-interaction=2 × 10-4), and total energy intake (High β:0.58 [0.51, 0.64] versus Low β:0.49 [0.42, 0.56] kg.m−2, P-interaction=0.019), but not for protein intake, carbohydrate intake and fiber intake (P-interaction &gt;0.05). The findings were broadly similar using WC as the outcome. Conclusions: These data suggest that the benefits of reducing the intake of fats and total energy intake, may be more important in individuals with high genetic risk for obesity