Hormonal contraceptive use, bone density and biochemical markers of bone metabolism in British Army recruits.

INTRODUCTION: Hormonal contraceptive use might impair bone health and increase the risk of stress fracture by decreasing endogenous oestrogen production, a central regulator of bone metabolism. This cross-sectional study investigated bone density and biochemical markers of bone metabolism in women taking hormonal contraceptives on entry to basic military training. METHODS: Forty-five female British Army recruits had biochemical markers of bone metabolism, areal bone mineral density (aBMD) and tibial speed of sound (tSOS) measured at the start of basic military training. Participants were compared by their method of hormonal contraception: no hormonal contraception (NONE), combined contraceptive pill (CP) or depot-medroxyprogesterone acetate (DMPA) (20±2.8 years, 1.64±0.63 m, 61.7±6.2 kg). RESULTS: aBMD was not different between groups (p≥0.204), but tSOS was higher in NONE (3%, p=0.014) when compared with DMPA users. Beta C-terminal telopeptide was higher in NONE (45%, p=0.037) and DMPA users (90%, p=0.003) compared with CP users. Procollagen type 1 N-terminal propeptide was higher in DMPA users compared with NONE (43%, p=0.045) and CP users (127%, p=0.001), and higher in NONE compared with CP users (59%, p=0.014). Bone alkaline phosphatase was higher in DMPA users compared with CP users (56%, p=0.044). CONCLUSIONS: DMPA use was associated with increased bone turnover and decreased cortical bone integrity of the tibia. Lower cortical bone integrity in DMPA users was possibly mediated by increased intracortical remodelling, but trabecular bone was not affected by contraceptive use.

Sedentary behaviour and bone health in older adults: a systematic review.

Older adults spend more than 8 h/day in sedentary behaviours. Detrimental effects of sedentary behaviour (SB) on health are established, yet little is known about SB and bone health (bone mineral density; BMD) in older adults. The purpose of this review is to examine associations of SB with BMD in older adults. Five electronic databases were searched: Web of Science (Core Collection); PubMed; EMBASE; Sports Medicine and Education and PsycInfo. Inclusion criteria were healthy older adults mean age ≥ 65 years; measured SB and measured BMD using dual-energy X-ray absorptiometry. Quality was assessed using National Institute of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. After excluding duplicates 17813 papers were assessed; 17757 were excluded on title/abstract, 49 at full text, resulting in two prospective and five cross-sectional observational studies reviewed. Four were rated 'good' and three were rated 'fair' using the quality assessment criteria. Findings varied across the studies and differed by gender. In women, four studies reported significant positive associations of SB with BMD at different sites, and two found significant negative associations. Five studies which examined both men and women, men reported negative or no associations of SB with femoral neck, pelvic, whole body, spine or leg BMD. Whilst these findings suggest differences between men and women in the associations of SB with BMD, they may be due to the varying anatomical sections examined for BMD, the different methods used to measure SB, the varied quality of the studies included and the limited number of published findings.

The effects of short-term low energy availability, achieved through diet or exercise, on cognitive function in oral contraceptive users and eumenorrheic women.

To date, no research has explored the effects of low energy availability on cognitive performance using dietary and exercise regimens relevant to athletes. Twenty female participants (10 eumenorrheic, 10 oral contraceptive [OC] users) completed three 3-day conditions: 1) controlled-balanced energy availability without exercise (BAL; 45 kcal·kg lean body mass [LBM]-1·day-1); 2) diet-induced low energy availability without exercise (DIET; 15 kcal·kg LBM-1·day-1); and 3) exercise-induced low energy availability (EX; 15 kcal·kg LBM-1·day-1, including 30 kcal·kg LBM-1·day-1 treadmill running at 70% maximal oxygen uptake). A cognitive test battery was completed before and after each 3-day condition. Mental rotation test accuracy improved in the BAL condition, but there was a decline in accuracy in the EX condition (BAL, +2.5%; EX, -1.4%; P = 0.042, d = 0.85). DIET (+1.3%) was not different to BAL or EX (P > 0.05). All other measures of cognitive performance were not affected by condition (P > 0.05) and OC use did not affect cognitive responses (P > 0.05). Accuracy in the mental rotation test was impaired when low energy availability was induced through increased exercise energy expenditure. All other aspects of cognition were unaffected by 3 days of low energy availability through diet or exercise. OC use did not mediate the effect of low energy availability on cognition. Novelty: Cognitive function was not affected by 3 days of diet-induced low energy availability. Only spatial awareness was impaired during 3 days of exercise-induced low energy availability. Reproductive hormones affected spatial awareness independent of energy availability.

Gestational hypercalcemia: Prevalence and biochemical profile.

Gestational hypercalcemia is associated with an increased risk of maternal, fetal and neonatal morbidity and mortality. Hypercalcemia may develop during pregnancy in individuals who were previously asymptomatic. The increased sensitivity during pregnancy may be related to physiological, gestational alterations in vitamin D and calcium metabolism and may be influenced by gene variants. The prevalence is unknown. We investigated the prevalence of hypercalcemia in trimester 3 (T3) in a population representative prospective cohort study (n = 1832) in South-West Sweden. Women with serum albumin (Alb) adjusted calcium (CaAlb) ≥ 2.65 mmol/L in T3 (n = 30) were matched to normo-calcemic controls, and markers of calcium and vitamin D metabolism were investigated in trimester 1 (T1) and T3. Serum concentrations of Ca, phosphate (P), Magnesium (Mg), Alb and creatinine (Cr), parathyroid hormone (PTH; T3 only), vitamin D metabolites (total 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, and free 25(OH)D) were analysed in T1 and T3. CaAlb (Payne; inter-laboratory difference: UEA = 0.15 + 0.9*UGOT; UEA 2.54 = UGOT 2.65) and estimated glomerular filtration rate (eGFR; modified 4-variable MDRD) and vitamin D metabolites ratios (VMR) were calculated. Normally and non-normally distributed data were presented as mean (SD) or median (95 %CI). Group differences in relationships between vitamin D metabolites and with PTH were investigated with multiple regression analyses. Hypercalcemia in T3 was found in 1.7 % of women. PTH concentrations suggestive of primary hyperparathyroidism was found in 1 woman and none had 25(OH)D or 24,25(OH)2D concentrations in the toxicity range or suggestive of mutations in the CYP24A1 gene. CaAlb was significantly higher in hypercalcemic cases compared to controls in T1 (2.44 (2.30-2.80) vs 2.37 (2.25-2.49) mmol/L) and T3 (2.63 (2.52-2.78) vs 2.46 (2.31-2.58) mmol/L). Serum P was higher among cases than controls in T3 (1.12 (0.16) vs 1.07 (0.18) mmol/L) but not in T1 (1.12 (0.18) and 1.12 (0.16) mmol/L). PTH in T3 was lower in cases (1.6 (1.6-2.8) vs 2.3 (2.1-2.8) pmol/L) but 1,25(OH)2D concentrations were similar. There were no significant group differences in serum 25(OH)D, free 25(OH)D, 24,25(OH)2D, Mg, Alb, Cr and eGFR. Regression analyses did not show significant differences between cases and controls in relationships between vitamin D metabolites and with PTH, except for the free 25(OH)D-PTH relationship and a higher free:total 25(OH)D ratio in cases at T1. In conclusion, most common causes of hypercalcemia were excluded in the majority of women. Hypercalcemic women had a relatively high serum 1,25(OH)2D concentration despite an appropriately suppressed PTH, suggestive of abnormal gestational adaptions.

Vaginal microbiome in early pregnancy and subsequent risk of spontaneous preterm birth: a case-control study.

OBJECTIVES: To explore differences in the vaginal microbiome between preterm and term deliveries. DESIGN: Nested case-control study in 3D cohort (design, develop, discover). SETTING: Quebec, Canada. SAMPLE: Ninety-four women with spontaneous preterm birth as cases [17 early (<34 weeks) and 77 late (34-36 weeks) preterm birth] and 356 women as controls with term delivery (≥37 weeks). METHODS: To assess the vaginal microbiome by sequencing the V4 region of the 16S ribosomal RNA (rRNA) gene in swabs self-collected during early pregnancy. MAIN OUTCOME MEASURES: Comparison of relative abundance of bacterial operational taxonomic units and oligotypes and identifying vaginal community state types (CSTs) in early or late spontaneous preterm and term deliveries. RESULTS: Lactobacillus gasseri/ Lactobacillus johnsonii (coefficient -5.36, 95% CI -8.07 to -2.65), Lactobacillus crispatus (99%)/ Lactobacillus acidophilus (99%) (-4.58, 95% CI -6.20 to -2.96), Lactobacillus iners (99%)/ Ralstonia solanacearum (99%) (-3.98, 95% CI -6.48 to -1.47) and Bifidobacterium longum/ Bifidobacterium breve (-8.84, 95% CI -12.96 to -4.73) were associated with decreased risk of early but not late preterm birth. Six vaginal CSTs were identified: four dominated by Lactobacillus; one with presence of bacterial vaginosis-associated bacteria (Gardnerella vaginalis, Atopobium vaginae and Veillonellaceae bacterium) (CST IV); and one with nondominance of Lactobacillus (CST VI). CST IV was associated with increased risk of early (4.22, 95% CI 1.24-24.85) but not late (1.63, 95% CI 0.68-5.04) preterm birth, compared with CST VI. CONCLUSIONS: Lactobacillus gasseri/L. johnsonii, L. crispatus/L. acidophilus, L. iners/R. solanacearum and B. longum/B. breve may be associated with decreased risk of early preterm birth. A bacterial vaginosis-related vaginal CST versus a CST nondominated by Lactobacillus may be associated with increased risk of early preterm birth. TWEETABLE ABSTRACT: Largest study of its kind finds certain species of vaginal Lactobacillus + Bifidobacterium may relate to lower risk of preterm birth.

Cord blood insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin, and their associations with insulin sensitivity, ß-cell function and adiposity in infancy.

AIM: Vulnerability to insulin resistance and Type 2 diabetes may originate in early life, but little is known about whether any perinatal biomarkers are predictive of later metabolic health. We sought to assess whether cord blood insulin, insulin-like growth factor (IGF)-I, IGF-II, leptin, adiponectin and ghrelin are associated with metabolic health indicators in infancy. METHODS: In a prospective singleton birth cohort, we assessed cord blood insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin concentrations in relation to the homeostasis model assessment of insulin resistance (HOMA-IR), ß-cell function (HOMA-ß), fasting proinsulin-to-insulin ratio, BMIz-score, and the sum of triceps and subscapular skinfold thickness (an indicator of adiposity) in infants at age 1 year (n = 185). RESULTS: Adjusting for maternal and infant characteristics, one standard deviation (sd) increase in cord blood adiponectin was associated with an 11.1% (95% confidence interval 1.8-19.5%) decrease in HOMA-ß (P = 0.02) and a 13.6% (1.8-26.8%) increase in proinsulin-to-insulin ratio (P = 0.02), indicating worse ß-cell function in infants at age 1 year. One sd increase in cord blood insulin was associated with a 0.5 (0.1-1.0) mm increase in skinfold thickness (P = 0.01). One sd increase in cord blood ghrelin was associated with a 0.2 (0.02-0.3) decrease in BMIz-score (P = 0.02) and a 0.5 (0.1-0.9) mm decrease (P = 0.02) in skinfold thickness. Cord blood IGF-I and IGF-II were not associated with the observed metabolic health indicators at age 1 year. CONCLUSION: The study is the first to show that cord blood adiponectin may be negatively predictive of ß-cell function, whereas cord blood ghrelin may be negatively predictive of adiposity in infancy.

Effect of soy on bone turn-over markers in men with type 2 diabetes and hypogonadism - a randomised controlled study.

Type 2 diabetes (T2DM) is associated with increased risk of fractures. Soy supplementation has been shown to have a beneficial effect on bone turnover markers (BTM) in postmenopausal women. However, the effect of soy supplementation on BTM in T2DM and particularly in men is unclear. We performed an analysis of a randomized double blind parallel study of 200 men with T2DM treated with soy, either with or without isoflavones. Outcome measures were type I collagen crosslinked beta C-telopeptide (ßCTX), and type 1 procollagen-N-propeptide (P1NP). The men, with a total testosterone <12 nmol/L, were treated with 15 g soy protein containing 66 mg of isoflavones (SPI) or 15 g soy protein alone without isoflavones (SP) daily for three months. There was a 15% reduction in ßCTX after three months of SPI compared to SP supplementation. There was no significant difference in P1NP with either SPI or SP supplementation. There was a significant linear correlation between the reduction in ßCTX in the SPI group with the reduction in HbA1c (r2 = 0.42; p = 0.04) and HOMA-IR (r2 = 0.54; p = 0.02). Our study indicates that there was a significant reduction in bone resorption following 3 months of SPI supplementation that correlated with an improvement of glycemic control in men with T2DM.

Longevity of daily oral vitamin D3 supplementation: differences in 25OHD and 24,25(OH)2D observed 2 years after cessation of a 1-year randomised controlled trial (VICtORy RECALL).

To determine how long vitamin D lasts after supplementation ceases, the marker of status was measured 2 and 3 years after a 1-year trial. Compared to placebo, the proportion of vitamin D-deficient women was still lower, if they had taken daily vitamin D3, after 2 years, indicating its longevity. INTRODUCTION: The purpose of this study was to determine longevity of vitamin D status following cessation of vitamin D3 supplementation, 2 and 3 years after a 1-year randomised, double-blind placebo controlled trial and to investigate possible predictive factors. METHODS: Caucasian non-smoking postmenopausal women randomised to ViCtORY (2009-2010), who had not taken vitamin D supplements since the trial ended, were invited to attend follow-up visits. Total 25-hydroxyvitamin D (25OHD) and 24,25-dihydroxyvitamin D (24,25OH2D) were measured by dual tandem mass spectrometry of serum samples following removal of protein and de-lipidation; the original randomised controlled trial (RCT) samples were re-analysed simultaneously. Vitamin D-binding protein (VDBP) was measured by monoclonal immunoassay. RESULTS: In March 2012 and March 2013, 159 women (mean (SD) age 67.6 (2.1) years) re-attended, equally distributed between the original treatment groups: daily vitamin D3 (400 IU, 1000 IU) and placebo. One month after the RCT ended (March 2010), the proportion of women in placebo, 400 IU and 1000 IU vitamin D3 groups, respectively, with 25OHD < 25 nmol/L was 15, 0 and 0 (chi-square p < 0.001, n = 46, 44, 54). After 2 years (March 2012), it was 22, 4 and 4% (p = 0.002, n = 50, 48, 57); after 3 years, it was 23, 13 and 15% (p = 0.429, n = 48, 45, 52). The respective proportions of women with 24,25OH2D < 2.2 nmol/L were 50, 2 and 2% (1 month, p < 0.001, n = 46, 44, 54); 42, 33 and 12% (2 years, p = 0.002, n = 50, 48, 57); and 45, 27 and 29% (3 years, p = 0.138, n = 47, 45, 51). VDBP was a predictor of circulating 25OHD longevity (beta for VDBP in µg/mL 0.736; 95% CI 0.216-1.255, p = 0.006) but not 24,25OH2D. CONCLUSION: Four hundred international units or 1000 IU of daily vitamin D3 showed benefits over placebo 2 years after supplementation ceased in keeping 25OHD > 25 nmol/L.

Does regional loss of bone density explain low trauma distal forearm fractures in men (the Mr F study)?

The pathogenesis of low trauma wrist fractures in men is not fully understood. This study found that these men have lower bone mineral density at the forearm itself, as well as the hip and spine, and has shown that forearm bone mineral density is the best predictor of wrist fracture. INTRODUCTION: Men with distal forearm fractures have reduced bone density at the lumbar spine and hip sites, an increased risk of osteoporosis and a higher incidence of further fractures. The aim of this case-control study was to investigate whether or not there is a regional loss of bone mineral density (BMD) at the forearm between men with and without distal forearm fractures. METHODS: Sixty-one men with low trauma distal forearm fracture and 59 age-matched bone healthy control subjects were recruited. All subjects underwent a DXA scan of forearm, hip and spine, biochemical investigations, health questionnaires, SF-36v2 and Fracture Risk Assessment Tool (FRAX). The non-fractured arm was investigated in subjects with fracture and both forearms in control subjects. RESULTS: BMD was significantly lower at the ultradistal forearm in men with fracture compared to control subjects, in both the dominant (mean (SD) 0.386 g/cm2 (0.049) versus 0.436 g/cm2 (0.054), p < 0.001) and non-dominant arm (mean (SD) 0.387 g/cm2 (0.060) versus 0.432 g/cm2 (0.061), p = 0.001). Fracture subjects also had a significantly lower BMD at hip and spine sites compared with control subjects. Logistic regression analysis showed that the best predictor of forearm fracture was ultradistal forearm BMD (OR = 0.871 (0.805-0.943), p = 0.001), with the likelihood of fracture decreasing by 12.9% for every 0.01 g/cm2 increase in ultradistal forearm BMD. CONCLUSIONS: Men with low trauma distal forearm fracture have significantly lower regional BMD at the ultradistal forearm, which contributes to an increased forearm fracture risk. They also have generalised reduction in BMD, so that low trauma forearm fractures in men should be considered as indicator fractures for osteoporosis.

Is maternal periconceptional smoking associated with 2D:4D digit ratio in their children?

The 2nd--4th finger ratio (2D:4D) has been proposed as a potential indicator of greater androgen exposure during fetal development. Maternal periconceptional smoking may alter the homeostasis of fetal androgens, which could in turn result in differential development of 2D:4Ds in utero. The aim of the present study was to assess the effect of maternal periconceptional smoking (i.e. 1 year before through the first trimester of pregnancy) on the 2D:4D of children within The Maternal-Infant Research on Environmental Chemicals (MIREC) study. Maternal smoking history was obtained through questionnaires during the first trimester of pregnancy in 2001 women from 10 cities across Canada. The periconceptional smoking prevalence was 12%. A follow-up study was conducted to measure growth and development up to 5 years of age in a subsample of some 800 MIREC children (MIREC-CD Plus), and digital pictures of the ventral surface of both hands were obtained in mothers and children (2-5 years). The 2D:4D was calculated as the ratio of the 2nd and 4th fingers of each hand. Boys had lower mean 2D:4Ds compared with girls in both hands. Age and maternal 2D:4D were strong determinants of the children's 2D:4D, however, the mean 2D:4D did not differ among children whose mothers had smoked during the periconceptional period compared with those who had not, irrespective of sex. In conclusion, we did not find an association between maternal periconceptional smoking and children's 2D:4D, although the smoking prevalence was low.

Reduced fetal vitamin D status by maternal undernutrition during discrete gestational windows in sheep.

Placental transport of vitamin D and other nutrients (e.g. amino acids, fats and glucose) to the fetus is sensitive to maternal and fetal nutritional cues. We studied the effect of maternal calorific restriction on fetal vitamin D status and the placental expression of genes for nutrient transport [aromatic T-type amino acid transporter-1 (TAT-1); triglyceride hydrolase/lipoprotein uptake facilitator lipoprotein lipase (LPL)] and vitamin D homeostasis [CYP27B1; vitamin D receptor (VDR)], and their association with markers of fetal cardiovascular function and skeletal muscle growth. Pregnant sheep received 100% total metabolizable energy (ME) requirements (control), 40% total ME requirements peri-implantation [PI40, 1-31 days of gestation (dGA)] or 50% total ME requirements in late gestation (L, 104-127 dGA). Fetal, but not maternal, plasma 25-hydroxy-vitamin D (25OHD) concentration was lower in PI40 and L maternal undernutrition groups (P<0.01) compared with the control group at 0.86 gestation. PI40 group placental CYP27B1 messenger RNA (mRNA) levels were increased (P<0.05) compared with the control group. Across all groups, higher fetal plasma 25OHD concentration was associated with higher skeletal muscle myofibre and capillary density (P<0.05). In the placenta, higher VDR mRNA levels were associated with higher TAT-1 (P<0.05) and LPL (P<0.01) mRNA levels. In the PI40 maternal undernutrition group only, reduced fetal plasma 25OHD concentration may be mediated in part by altered placental CYP27B1. The association between placental mRNA levels of VDR and nutrient transport genes suggests a way in which the placenta may integrate nutritional cues in the face of maternal dietary challenges and alter fetal physiology.

High Bone Mass is associated with bone-forming features of osteoarthritis in non-weight bearing joints independent of body mass index.

OBJECTIVES: High Bone Mass (HBM) is associated with (a) radiographic knee osteoarthritis (OA), partly mediated by increased BMI, and (b) pelvic enthesophytes and hip osteophytes, suggestive of a bone-forming phenotype. We aimed to establish whether HBM is associated with radiographic features of OA in non-weight-bearing (hand) joints, and whether such OA demonstrates a bone-forming phenotype. METHODS: HBM cases (BMD Z-scores≥+3.2) were compared with family controls. A blinded assessor graded all PA hand radiographs for: osteophytes (0-3), joint space narrowing (JSN) (0-3), subchondral sclerosis (0-1), at the index Distal Interphalangeal Joint (DIPJ) and 1st Carpometacarpal Joint (CMCJ), using an established atlas. Analyses used a random effects logistic regression model, adjusting a priori for age and gender. Mediating roles of BMI and bone turnover markers (BTMs) were explored by further adjustment. RESULTS: 314 HBM cases (mean age 61.1years, 74% female) and 183 controls (54.3years, 46% female) were included. Osteophytes (grade≥1) were more common in HBM (DIPJ: 67% vs. 45%, CMCJ: 69% vs. 50%), with adjusted OR [95% CI] 1.82 [1.11, 2.97], p=0.017 and 1.89 [1.19, 3.01], p=0.007 respectively; no differences were seen in JSN. Further adjustment for BMI failed to attenuate ORs for osteophytes in HBM cases vs. controls; DIPJ 1.72 [1.05, 2.83], p=0.032, CMCJ 1.76 [1.00, 3.06], p=0.049. Adjustment for BTMs (concentrations lower amongst HBM cases) did not attenuate ORs. CONCLUSIONS: HBM is positively associated with OA in non-weight-bearing joints, independent of BMI. HBM-associated OA is characterised by osteophytes, consistent with a bone-forming phenotype, rather than JSN reflecting cartilage loss. Systemic factors (e.g. genetic architecture) which govern HBM may also increase bone-forming OA risk.

The relationship between vitamin D status and muscle strength in young healthy adults from sunny climate countries currently living in the northeast of Scotland.

The current study examined the relationship between vitamin D status and muscle strength in young healthy adults: residents (>6 months) and newcomers (0-3 months), originally from sunny climate countries but currently living in the northeast of Scotland. Our longitudinal data found a positive, albeit small, relationship between vitamin D status and knee extensor isometric strength. INTRODUCTION: Vitamin D has been suggested to play a role in muscle health and function, but studies so far have been primarily in older populations for falls prevention and subsequent risk of fractures. METHODS: Vitamin D status was assessed in a healthy young adults from sunny climate countries (n = 71, aged 19-42 years) with 56% seen within 3 months of arriving in Aberdeen [newcomers; median (range) time living in the UK = 2 months (9-105 days)] and the remainder resident for >6 months [residents; 23 months (6-121 months)]. Participants attended visits every 3 months for 15 months. At each visit, fasted blood samples were collected for analysis of serum 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), carboxy-terminal collagen crosslinks (CTX) and N-terminal propeptide of type I collagen (P1NP). Maximal voluntary contractions (MVC) were performed for grip strength (both arms) and for maximal isometric strength of the knee extensors (right knee). RESULTS: There were small seasonal variations in 25(OH)D concentrations within the newcomers and residents, but no seasonal variation in bone turnover markers. There was a positive, albeit small, association between 25(OH)D and knee extensor maximal isometric strength. Mixed modelling predicted that for each 1 nmol/L increase in 25(OH)D, peak torque would increase by 1 Nm (p = 0.04). CONCLUSIONS: This study suggests that vitamin D may be important for muscle health in young adults migrating from sunnier climates to high latitudes, yet the potential effect is small.

Habitual levels of higher, but not medium or low, impact physical activity are positively related to lower limb bone strength in older women: findings from a population-based study using accelerometers to classify impact magnitude.

This study assessed the effect of accelerometry-measured higher impacts resulting from habitual weight-bearing activity on lower limb bone strength in older women. Despite higher impacts being experienced rarely in this population-based cohort, positive associations were observed between higher vertical impacts and lower limb bone size and strength. INTRODUCTION: We investigated whether the benefit of habitual weight-bearing physical activity (PA) for lower limb bone strength in older women is explained by exposure to higher impacts, as previously suggested by observations in younger individuals. METHODS: Four hundred and eight women from the Cohort for Skeletal Health in Bristol and Avon (COSHIBA), mean 76.8 years, wore tri-axial accelerometers at the waist for a mean of 5.4 days. Y-axis peaks were categorised, using previously identified cutoffs, as low (0.5-1.0 g), medium (1.0-1.5 g), and higher (≥1.5 g) impacts. Mid and distal peripheral quantitative computed tomography scans of the tibia and radius were performed, as were hip and lumbar spine Dual X-ray Absorptiometry (DXA) scans. Regressions between (log transformed) number of low, medium and high impacts, and bone outcomes were adjusted for artefact error grade, age, height, fat and lean mass and impacts in other bands. RESULTS: Eight thousand eight hundred and nine (4047, 16,882) low impacts were observed during the measurement week, 345 (99, 764) medium impacts and 42 (17, 106) higher impacts (median with 25th and 75th quartiles). Higher vertical impacts were positively associated with lower limb bone strength as reflected by cross-sectional moment of inertia (CSMI) of the tibia [0.042 (0.012, 0.072) p = 0.01] and hip [0.067 (0.001, 0.133) p = 0.045] (beta coefficients show standard deviations change per doubling in impacts, with 95 % confidence interval). Higher impacts were positively associated with tibial periosteal circumference (PC) [0.015 (0.003, 0.027) p = 0.02], but unrelated to hip BMD. Equivalent positive associations were not seen for low or medium impacts. CONCLUSIONS: Despite their rarity, habitual levels of higher impacts were positively associated with lower limb bone size and strength, whereas equivalent relationships were not seen for low or medium impacts.

Pre-eclampsia and risk of infantile haemangioma.

BACKGROUND: Infantile haemangioma is the most common tumour of infancy, but the association with pre-eclampsia is poorly understood. OBJECTIVES: We determined the relationship between variants of pre-eclampsia and risk of infantile haemangioma. METHODS: We carried out a retrospective cohort study of hospital data for all live births between 1989 and 2013 in Quebec, Canada. We identified 14 240 neonates with, and 1 930 564 without haemangioma before discharge, and determined whether early- or late-onset pre-eclampsia was documented on the maternal chart. We used log-binomial regression to compute prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association between pre-eclampsia and infantile haemangioma, adjusted for maternal characteristics. RESULTS: The prevalence of any haemangioma was higher for pre-eclampsia than for no pre-eclampsia (81·3 vs. 72·9 per 10 000), with a PR of 1·15 (95% CI 1·06-1·25) after adjustment for maternal characteristics. Pre-eclampsia with onset before 34 weeks' gestation was associated with cutaneous (PR 2·32, 95% CI 1·68-3·21), noncutaneous (PR 3·66, 95% CI 2·49-5·37) and unspecified haemangioma (PR 2·49, 95% CI 1·77-3·49). However, the association between early-onset pre-eclampsia and haemangioma was attenuated once long neonatal length of hospital stays was accounted for. There was no association with late-onset pre-eclampsia after 34 weeks, and associations were weaker for other variants including severe pre-eclampsia and pre-eclampsia with low birthweight. CONCLUSIONS: Early-onset pre-eclampsia is associated with increased risk of haemangioma at birth, but detection bias due to longer hospital stays and closer follow-up may be part of the reason.

Female digit length ratio (2D:4D) and time-to-pregnancy.

STUDY QUESTION: Is the female 2th- to 4th-finger ratio (2D:4D) associated with fecundity as measured by time-to-pregnancy (TTP)? SUMMARY ANSWER: Our study does not support an association between female 2D:4D and TTP. WHAT IS KNOWN ALREADY: The 2th- to 4th-finger ratio (2D:4D) has been proposed as a potential indicator of greater androgen exposure during fetal development. Women exposed in utero to unbalanced steroid hormones may have impaired fecundity in the adulthood. Fecundity is often measured by TTP, an epidemiological tool commonly used to assess the impact of environmental factors in human conception. STUDY DESIGN, SIZE, DURATION: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study is a pregnancy and birth cohort of 2001 women recruited before 14 weeks of gestation in 10 cities across Canada between 2008 and 2011. The present analysis is part of MIREC-CD Plus, a follow-up study in a subsample of some 800 MIREC mothers and their children from 2012 to 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: TTP and maternal characteristics were collected from questionnaires administered during the first trimester of pregnancy as part of the MIREC study. Digital pictures of the ventral surface of both hands were obtained in the MIREC mothers at the MIREC-CD Plus follow-up study. The 2D:4D was calculated as the ratio of the second and fourth fingers of each hand. The exposure of interest was the 2D:4D of the women categorized by tertiles, or dichotomized as ≥1 (index finger longer than the ring finger) or <1 (ring finger longer than the index finger, implying greater androgen exposure during fetal development). The final sample included 696 mothers. Statistical analyses included discrete-time Cox proportional hazard models, allowing adjustment for potential confounding factors. MAIN RESULTS AND THE ROLE OF CHANCE: There was no evidence of diminished/increased fecundability according to the 2D:4D, neither on the right nor on the left hand. In our analysis by tertiles, the smallest 2D:4D (i.e. higher androgen exposure during fetal life) resulted in FORs higher than 1 (i.e. shorter TTP) in both hands, although this was not statistically significant (FOR 1.19 [95% CI 0.93, 1.51] in the right hand and 1.16 [95% CI 0.91, 1.47] in the left hand). In the dichotomous analysis, 2D:4D <1 resulted in FORs higher than 1 (i.e. shorter TTP), but this was also not statistically significant (FOR 1.08 [95% CI 0.88, 1.33] in the right hand and 1.14 [95% CI 0.92, 1.42] in the left hand). Our large sample size resulted in a high statistical power to exclude an association between female 2D:4D and TTP. LIMITATIONS, REASONS FOR CAUTION: The MIREC Study is a cohort of pregnant women, and therefore, women with infertility were excluded by design from our study. WIDER IMPLICATIONS OF THE FINDINGS: Our data do not provide evidence for an association between female 2D:4D and fecundity as measured by TTP. Whether the female 2D:4D is a marker of in utero androgen exposure and whether it is associated with fecundity have yet to be determined. STUDY FUNDING/COMPETING INTEREST: The MIREC Study was funded by Health Canada's Chemicals Management Plan, the Canadian Institute of Health Research (CIHR grant # MOP - 81285), and the Ontario Ministry of the Environment. MIREC-CD Plus was funded by Health Canada's Chemicals Management Plan Research Fund. The 2D:4D component was funded by a research grant from the CIHR-Quebec Training Network in Perinatal Research (QTNPR). M.P. Vélez was supported by a CIHR Fellowship Award, and a QTNPR scholarship. P. Monnier is supported by the Research Institute of the McGill University Health Centre. W.D Fraser is supported by a CIHR Canada Research Chair. There are no conflicts of interest to declare.

Longitudinal circulating concentrations of long-chain polyunsaturated fatty acids in the third trimester of pregnancy in gestational diabetes.

AIM: Gestational diabetes mellitus is a common complication of pregnancy. Long-chain polyunsaturated fatty acids (LCPUFA) are essential for fetal neurodevelopment. Docosahexaenoic acid (DHA) is the predominant n-3 LCPUFA in the brain and retina. Circulating absolute concentrations of total n-3 and n-6 LCPUFAs rise during normal pregnancy. It remains unclear whether gestational diabetes may affect the normal rise in circulating concentrations of LCPUFAs in the third trimester of pregnancy - a period of rapid fetal neurodevelopment. This study aimed to address this question. METHODS: In a prospective singleton pregnancy cohort, fatty acids in fasting plasma total lipids were measured at 24-28 and 32-35 weeks of gestation in women with (n = 24) and without gestational diabetes mellitus (n = 116). Fatty acid desaturase activity indices were estimated by relevant product-to-precursor fatty acid ratios. Dietary nutrient intakes were estimated by a food frequency questionnaire. RESULTS: Plasma absolute concentrations of total n-6 LCPUFAs rose significantly between 24-28 and 32-35 weeks of gestation in women with or without gestational diabetes, whereas total n-3 LCPUFAs and DHA concentrations rose significantly only in women without gestational diabetes (all P < 0.01). Delta-5 desaturase indices (20:4n-6/20:3n-6) were similar, but delta-6 desaturase indices (18:3n-6/18:2n-6) were significantly lower in women with gestational diabetes at 32-35 weeks of gestation. Dietary intakes of all fatty acids were comparable. CONCLUSION: The normal rise in circulating absolute concentrations of DHA and total n-3 LCPUFAs in the third trimester of pregnancy may be compromised in gestational diabetes, probably due to impaired synthesis or mobilization rather than dietary intake difference.

Seroconversion for cytomegalovirus infection in a cohort of pregnant women in Québec, 2010-2013.

Cytomegalovirus (CMV) is the leading cause of congenital infection and non-genetic sensorineural hearing loss in children. There are no recent data on the incidence of CMV infection during pregnancy in Canada. This present study was undertaken to determine the seroprevalence of CMV IgG antibodies and the rate of seroconversion in a cohort of pregnant women in the province of Québec, Canada. We used serum samples and questionnaire data collected as part of the 3D Pregnancy and Birth Cohort Study (2010-2013) conducted in Québec, Canada. CMV IgG antibodies were determined in serum samples collected at the first and third trimesters. Associations between independent variables and seroprevalence were assessed using logistic regression, and associations with seroconversions, by Poisson regression. Of 1938 pregnant women tested, 40·4% were seropositive for CMV at baseline. Previous CMV infection was associated with: working as a daycare educator, lower education, lower income, having had children, first language other than French or English, and being born outside Canada or the United States. Of the 1122 initially seronegative women, 24 (2·1%) seroconverted between their first and third trimesters. The seroconversion rate was 1·4 [95% confidence interval (CI) 0·9-2·1]/10 000 person-days at risk or 3·9 (95% CI 2·5-5·9)/100 pregnancies (assuming a 280-day gestation). The high proportion of pregnant women susceptible to CMV infection (nearly 60%) and the subsequent rate of seroconversion are of concern.

Maternal exposure to perfluorinated chemicals and reduced fecundity: the MIREC study.

STUDY QUESTION: What is the effect of maternal exposure to perfluorooctane sulfonate (PFOS), perflurooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS) on female fecundity? SUMMARY ANSWER: Increasing concentrations of PFOA or PFHxS in maternal plasma were associated with reduced fecundability and infertility. WHAT IS KNOWN ALREADY: Perfluorinated chemicals (PFCs) are a group of synthetic compounds used in industrial production. There is a concern about the effect of PFCs on fecundity, as measured by time-to-pregnancy (TTP). Although some recent studies suggest that increasing concentrations of PFCs may decrease fecundity, divergence in the methodological approaches used to evaluate this association have prevented firm conclusions being reached. STUDY DESIGN, SIZE, DURATION: The Maternal-Infant Research on Environmental Chemicals (MIREC) Study is a cohort study of 2,001 women recruited before 14 weeks of gestation in 10 cities across Canada between 2008 and 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: A questionnaire was administered and medical chart data and biospecimens were collected from participants. After excluding women who withdrew, those for whom data were incomplete, those whose pregnancies followed birth control failure, and accounting for male fertility, 1743 participants remained. TTP was defined as the number of months of unprotected intercourse needed to become pregnant in the current pregnancy, as self-reported in the first trimester of pregnancy. Plasma concentrations of PFOA, PFOS and PFHxS measured in the first trimester were considered as a surrogate of preconception exposure. Fecundability odds ratios (FORs) were estimated using Cox proportional hazard models for discrete time. FOR < 1 denote a longer TTP and FORs >1 denote a shorter TTP. The odds of infertility (TTP > 12 months or infertility treatment in the index pregnancy) were estimated using logistic regression. Each chemical concentration (ng/ml) was log-transformed and divided by its SD. MAIN RESULTS AND THE ROLE OF CHANCE: The cumulative probabilities of pregnancy at 1, 6 and 12 months were 0.42 (95% confidence interval (CI) 0.40-0.45), 0.81 (95% CI 0.79-0.83) and 0.90 (95% CI 0.89-0.92), respectively. The mean maternal age was 32.8 (SD 5.0) years. The geometric means (ng/ml) of PFOA, PFOS and PFHxS were 1.66 (95% CI 1.61-1.71), 4.59 (95% CI 4.46-4.72) and 1.01 (95% CI 0.97-1.05), respectively. After adjustment for potential confounders, PFOA and PFHxS were associated with a 11 and 9% reduction in fecundability per one SD increase (FOR = 0.89; 95% CI 0.83-0.94; P < 0.001 for PFOA and FOR = 0.91; 95% CI 0.86-0.97; P = 0.002 for PFHxS), while no significant association was observed for PFOS (FOR = 0.96; 95% CI 0.91-1.02; P = 0.17). In addition, the odds of infertility increased by 31% per one SD increase of PFOA (odds ratio (OR) = 1.31; 95% CI 1.11-1.53; P = 0.001) and by 27% per one SD increase of PFHxS (OR = 1.27; 95% CI 1.09-1.48; P = 0.003), while no significant association was observed for PFOS (OR = 1.14; 95% CI 0.98-1.34; P = 0.09). LIMITATIONS, REASONS FOR CAUTION: Women with the highest concentrations of PFCs might have been excluded from the study if there is a causal association with infertility. The MIREC study did not assess concentrations of PFCs in males, semen quality, menstrual cycle characteristics or intercourse frequency. WIDER IMPLICATIONS OF THE FINDINGS: Our results add to the evidence that exposure to PFOA and PFHxS, even at lower levels than previously reported, may reduce fecundability. STUDY FUNDING/COMPETING INTERESTS: The MIREC study is supported by the Chemicals Management Plan of Health Canada, the Canadian Institutes for Health Research (CIHR, grant no. MOP - 81285) and the Ontario Ministry of the Environment. M.P.V. was supported by a CIHR Fellowship Award, and a CIHR-Quebec Training Network in Perinatal Research (QTNPR) Ph.D. scholarship. W.D.F. is supported by a CIHR Canada Research Chair. There are no conflicts of interest to declare.