UK stillbirth trends in over 11 million births provide no evidence to support effectiveness of Growth Assessment Protocol program.

OBJECTIVE: Use of the Growth Assessment Protocol (GAP) has increased internationally under the assumption that it reduces the stillbirth rate. The evidence for this is limited and based largely on an ecological time-trend study. Discordance in the uptake of the GAP program between Scotland and England/Wales enabled us to assess the assertion that implementation of GAP leads to a reduced stillbirth rate. METHODS: We analyzed data from the National Records for Scotland and the Office for National Statistics on the number of singleton maternities and stillbirths in Scotland and in England and Wales, respectively, from 1 January 2000 to 31 December 2015. National uptake of the GAP program over time in each of the regions was recorded. Stillbirth rate per 1000 maternities was calculated, according to year of delivery, and compared between Scotland and England/Wales. RESULTS: During the study period, there were 870 632 singleton maternities in Scotland, of which 4243 were stillbirths, and there were 10 469 120 singleton maternities in England and Wales, of which 51 562 were stillbirths. There was a marked difference in uptake of the GAP program between the two regions, with substantially fewer maternity units in Scotland implementing the program. Stillbirth rates were static up to 2010, with a decline thereafter in both regions, to 3.75 (95% CI, 3.25-4.30) per 1000 maternities in Scotland and 4.30 (95% CI, 4.15-4.46) per 1000 maternities in England and Wales in 2015. From 2010 onwards, the decline in Scotland was faster, equating to 48 (95% CI, 47.9-48.1) fewer stillbirths per 100 000 maternities in Scotland than in England and Wales from 2010 to 2015 compared with 2000 to 2009. CONCLUSIONS: We observed a decline in stillbirth rate in England and Wales, which coincided with implementation of the GAP program. However, a concurrent decline in stillbirth rate was observed in Scotland in the absence of increased implementation of GAP. The secular rates of change in stillbirth rate in England and Wales cannot be used to infer efficacy of the GAP program. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Variation in menopausal vasomotor symptoms outcomes in clinical trials: a systematic review.

BACKGROUND: There is substantial variation in how menopausal vasomotor symptoms are reported and measured among intervention studies. This has prevented meaningful comparisons between treatments and limited data synthesis. OBJECTIVES: To review systematically the outcome reporting and measures used to assess menopausal vasomotor symptoms from randomised controlled trials of treatments. SEARCH STRATEGY: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to May 2018. SELECTION CRITERIA: Randomised controlled trials with a primary outcome of menopausal vasomotor symptoms in women and a sample size of at least 20 women per study arm. DATA COLLECTION AND ANALYSIS: Data about study characteristics, primary vasomotor-related outcomes and methods of measuring them. MAIN RESULTS: The search identified 5591 studies, 214 of which were included. Forty-nine different primary reported outcomes were identified for vasomotor symptoms and 16 different tools had been used to measure these outcomes. The most commonly reported outcomes were frequency (97/214), severity (116/214), and intensity (28/114) of vasomotor symptoms or a composite of these outcomes (68/214). There was little consistency in how the frequency and severity/intensity of vasomotor symptoms were defined. CONCLUSIONS: There is substantial variation in how menopausal vasomotor symptoms have been reported and measured in treatment trials. Future studies should include standardised outcome measures which reflect the priorities of patients, clinicians, and researchers. This is most effectively achieved through the development of a Core Outcome Set. This systematic review is the first step towards development of a Core Outcome Set for menopausal vasomotor symptoms. TWEETABLE SUMMARY: Menopausal hot flushes and night sweats have been reported in 49 different ways in clinical research. A core outcome set is urgently required.

Urinary Sodium Excretion, Blood Pressure, and Risk of Future Cardiovascular Disease and Mortality in Subjects Without Prior Cardiovascular Disease.

Hypertension is a risk factor for cardiovascular disease. Increased urinary sodium excretion, representing dietary sodium intake, is associated with hypertension. Low sodium intake has been associated with increased mortality in observational studies. Further studies should assess whether confounding relationships explain associations between sodium intake and outcomes. We studied UK Biobank participants (n=457 484; mean age, 56.3 years; 44.7% men) with urinary electrolytes and blood pressure data. Estimated daily urinary sodium excretion was calculated using Kawasaki formulae. We analyzed associations between sodium excretion and blood pressure in subjects without cardiovascular disease, treated hypertension, or diabetes mellitus at baseline (n=322 624). We tested relationships between sodium excretion, incidence of fatal and nonfatal cardiovascular disease, heart failure, and mortality. Subjects in higher quintiles of sodium excretion were younger, with more men and higher body mass index. There was a linear relationship between increasing urinary sodium excretion and blood pressure. During median follow-up of 6.99 years, there were 11 932 deaths (1125 cardiovascular deaths) with 10 717 nonfatal cardiovascular events. There was no relationship between quintile of sodium excretion and outcomes. These relationships were unchanged after adjustment for comorbidity or excluding subjects with events during the first 2 years follow-up. No differing risk of incident heart failure (1174 events) existed across sodium excretion quintiles. Urinary sodium excretion correlates with elevated blood pressure in subjects at low cardiovascular risk. No pattern of increased cardiovascular disease, heart failure, or mortality risk was demonstrated with either high or low sodium intake.

Associations of dietary protein intake with bone mineral density: An observational study in 70,215 UK Biobank participants.

PURPOSE: Adequate dietary protein intake is important for the maintenance of bone health; however, data in this area is ambiguous with some suggestion that high protein intake can have deleterious effects on bone health. The aim of the current study was to explore the associations of protein intake with bone mineral density (BMD). METHODS: We used baseline data from the UK Biobank (participants aged 40-69 years) to examine the association of protein intake with BMD (measured by ultrasound). These associations were examined, in women (n = 39,066) and men (n = 31,149), after adjustment for socio-demographic and lifestyle confounders and co-morbidities. RESULTS: Protein intake was positively and linearly associated with BMD in women (ß-coefficient 0.010 [95% CI 0.005; 0.015, p < 0.0001]) and men (ß-coefficient 0.008 [95% CI 0.000; 0.015, p = 0.044]); per 1.0 g/kg/day increment in protein intake, independently of socio-demographics, dietary factors and physical activity. CONCLUSIONS: The current data have demonstrated that higher protein intakes are positively associated with BMD in both men and women. This indicates that higher protein intakes may be beneficial for both men and women.

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 in 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-single-nucleotide polymorphism (SNP) GPRS was associated with a higher BMI (ß: 0.57 kg m-2 per s.d. increase in GPRS (95% confidence interval: 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 (ß: 0.50 (0.44, 0.57) kg m-2). Significant interactions with similar patterns were observed for saturated fat intake (high ß: 0.66 (0.59, 0.73) versus low ß: 0.49 (0.42, 0.55) kg m-2, P(interaction)=2 × 10-4) and for total energy intake (high ß: 0.58 (0.51, 0.64) versus low ß: 0.49 (0.42, 0.56) kg m-2, P(interaction)=0.019), but not for protein intake, carbohydrate intake and fibre intake (P(interaction) >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.

Adiposity among 132 479 UK Biobank participants; contribution of sugar intake vs other macronutrients.

Background: Policy makers are being encouraged to specifically target sugar intake in order to combat obesity. We examined the extent to which sugar, relative to other macronutrients, was associated with adiposity. Methods: We used baseline data from UK Biobank to examine the associations between energy intake (total and individual macronutrients) and adiposity [body mass index (BMI), percentage body fat and waist circumference]. Linear regression models were conducted univariately and adjusted for age, sex, ethnicity and physical activity. Results: Among 132 479 participants, 66.3% of men and 51.8% of women were overweight/obese. There was a weak correlation (r = 0.24) between energy from sugar and fat; 13% of those in the highest quintile for sugar were in the lowest for fat, and vice versa. Compared with normal BMI, obese participants had 11.5% higher total energy intake and 14.6%, 13.8%, 9.5% and 4.7% higher intake from fat, protein, starch and sugar, respectively. Hence, the proportion of energy derived from fat was higher (34.3% vs 33.4%, P < 0.001) but from sugar was lower (22.0% vs 23.4%, P < 0.001). BMI was more strongly associated with total energy [coefficient 2.47, 95% confidence interval (CI) 2.36-2.55] and energy from fat (coefficient 1.96, 95% CI 1.91-2.06) than sugar (coefficient 0.48, 95% CI 0.41-0.55). The latter became negative after adjustment for total energy. Conclusions: Fat is the largest contributor to overall energy. The proportion of energy from fat in the diet, but not sugar, is higher among overweight/obese individuals. Focusing public health messages on sugar may mislead on the need to reduce fat and overall energy consumption.

Resistin in mid-trimester amniotic fluid in trisomy 21.

OBJECTIVE: The aim of this study was to examine whether resistin is present in second trimester amniotic fluid from trisomy 21 (also known as Down's syndrome) pregnancies and whether its concentration differs compared with euploid pregnancies. METHODS: The study cohort consisted of 58 women in the mid-trimester of pregnancy who underwent amniocentesis for prenatal diagnosis, 31 of whom carried a single fetus with diagnosed trisomy 21 (study group) and the rest with normal karyotype (control group, n = 27). Groups were matched for maternal and gestational age. Levels of resistin in amniotic fluid were measured by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Resistin was detected in all amniotic fluid samples. Its median concentration in the second trimester amniotic fluid of trisomy 21 pregnancies (2.1 ng/ml) was statistically significantly lower (p value <0.001) in comparison with that in euploid pregnancies (3.3 ng/ml). CONCLUSIONS: Resistin is a physiologic constituent of second trimester amniotic fluid. Lower levels of amniotic fluid resistin in pregnancies with trisomy 21 may reflect altered metabolic pathways in utero that could possibly be related with phenotypic features of the syndrome.

Corticotropin-releasing hormone and progesterone plasma levels association with the onset and progression of labor.

UNLABELLED: PURPOSE OF LNVESTIGATION: To examine the relationship between maternal plasma progesterone along with corticotropin- releasing hormone (CRH) plasma levels and the progression of labor. MATERIALS AND METHODS: Maternal serum CRH and progesterone were measured during the latent phase of labor, active labor, and 24 hours postpartum in women who went into spontaneous labor and delivered vaginally at term. Progesterone (P) levels in women delivered by an elective cesarean section at term were also measured as baseline. RESULTS: Mean maternal plasma P was 18% higher in the active phase than in the latent phase of labor (p < 0.01), and declined significantly by 24 hours postpartum (p < 0.001). Mean level of serum CRH was 24% higher in the active phase than in the latent phase of labor (p < 0.01), and subsequently declined significantly by 24 hours postpartum (p < 0.001). CONCLUSIONS: As labor progresses, P and CRH increase and subsequently decrease precipitously in the immediate postpartal period. P levels tend to drop in women who are in early labor compared with non-laboring full-term women.

Mediators of chronic inflammation in polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is an endocrine disorder affecting 5-10% of reproductive-age women. Hyperandrogenemia, which characterizes the syndrome, stimulates the maturation of adipocytes and favors central obesity. The linking hub between obesity and other metabolic manifestations of the syndrome seems to be chronic low-grade inflammation. We discuss the most reliable current data regarding the role of inflammatory mediators in PCOS, with particular focus on the genetic mechanisms implicated. C-reactive protein levels are 96% higher in PCOS patients than in healthy controls. Patients with the -308A polymorphism of the tumor necrosis factor-α gene have elevated androgens in comparison with carriers of the -308G. Interleukin 18 (IL-18) is elevated in lean patients, with a further rise in the presence of obesity and insulin resistance. Polymorphisms of the IL-1a, IL-1b and IL-6 genes have also been associated with PCOS. Plasminogen activator inhibitor-1 levels are positively associated with the syndrome, and carriers of the 4G allele of the 4G/5G polymorphism are at risk of developing PCOS. Other mediators discussed include adhesion molecules, osteoprotegerin, asymmetric dimethylarginine, homocysteine and advanced glycation end-products. The elucidation of the pathogenetic mechanisms implicated in PCOS and their connection with low-grade inflammation may in the future offer the opportunity for the formulation of novel therapeutic strategies and individualized therapy for these patients.

Fetuin A concentration in the second trimester amniotic fluid of fetuses with trisomy 21 appears to be lower: phenotypic considerations.

OBJECTIVE: We investigated whether the concentration of the glycoprotein fetuin A is altered in the second trimester amniotic fluid of trisomy 21 pregnancies compared with euploid pregnancies. METHODS: 25 pregnancies with an extra chromosome 21 were matched for maternal and gestational age with 25 pregnancies with normal karyotype. Levels of fetuin A in amniotic fluid were measured by a commercially available enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: The median concentration of fetuin A in amniotic fluid of trisomy 21 pregnancies (5.3 ng/ml) was statistically significantly lower (P value = 0.008) compared with that in euploid pregnancies (6.8 ng/mL). CONCLUSION: Lower levels of fetuin A in trisomy 21 may indicate an association with altered metabolic pathways in this early stage that could potentially be associated with features of the syndrome, such as growth restriction or impaired osteogenesis.