Associations between antenatal depressive symptoms in different trimesters and perinatal outcomes: A prospective multicenter cohort study in China.

BACKGROUND: Evidence exists that maternal antenatal depression may have adverse impacts on perinatal outcomes. However, the results of those studies are inconsistent and mainly focus on maternal depressive symptoms in the second or third trimester. METHODS: This prospective cohort study used a sub-sample of participants from the Sino-Canadian Healthy Life Trajectories Initiative trial. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for depressive symptoms in the first, second, and third trimesters, respectively. Infant growth indicator measurements were conducted in the first year of life. Logistic regression, Spearman correlation analyses and Generalized estimation equation (GEE) models were used to test the hypotheses. RESULTS: 2053 participants were recruited in this study, 326 of whom had at least one EPDS score ≥ 10 during pregnancy. A higher EPDS score in the first (aOR=1.053, 95 % CI: 1.004-1.103) or in the second trimester (aOR=1.060, 95 % CI: 1.007-1.115) was associated with greater risk of macrosomia. A higher EPDS score in the third trimester was associated with higher risks of preterm birth (aOR=1.079, 95 % CI: 1.006-1.157) and the infant being small for gestational age (aOR=1.097, 95 % CI: 1.015-1.185). GEE models showed that a greater EPDS score in the third trimester was associated with higher infant subscapular skinfold thickness (adjusted ß=0.026, 95 % CI: 0.003-0.050). CONCLUSION: Maternal depressive symptoms in different trimesters were differentially associated with infant weight and growth parameters at birth and postnatally. The present study further highlights the importance of depression screening in all trimesters of pregnancy, including the first trimester.

Effect of Menstrual Cycle and Hormonal Contraception on Musculoskeletal Health and Performance: Protocol for a Prospective Cohort Design and Cross-Sectional Comparison.

BACKGROUND: Women of reproductive age experience cyclical variation in the female sex steroid hormones 17ß-estradiol and progesterone during the menstrual cycle that is attenuated by some hormonal contraceptives. Estrogens perform a primary function in sexual development and reproduction but have nonreproductive effects on bone, muscle, and sinew tissues (ie, ligaments and tendons), which may influence injury risk and physical performance. OBJECTIVE: The purpose of the study is to understand the effect of the menstrual cycle and hormonal contraceptive use on bone and calcium metabolism, and musculoskeletal health and performance. METHODS: A total of 5 cohorts of physically active women (aged 18-40 years) will be recruited to participate: eumenorrheic, nonhormonal contraceptive users (n=20); combined oral contraceptive pill (COCP) users (n=20); hormonal implant users (n=20); hormonal intrauterine system users (n=20); and hormonal injection users (n=20). Participants must have been using the COCP and implant for at least 1 year and the intrauterine system and injection for at least 2 years. First-void urine samples and fasted blood samples will be collected for biochemical analysis of calcium and bone metabolism, hormones, and metabolic markers. Knee extensor and flexor strength will be measured using an isometric dynamometer, and lower limb tendon and stiffness, tone, and elasticity will be measured using a Myoton device. Functional movement will be assessed using a single-leg drop to assess the frontal plane projection angle and the qualitative assessment of single leg loading. Bone density and macro- and microstructure will be measured using ultrasound, dual-energy x-ray absorptiometry, and high-resolution peripheral quantitative computed tomography. Skeletal material properties will be estimated from reference point indentation, performed on the flat surface of the medial tibia diaphysis. Body composition will be assessed by dual-energy x-ray absorptiometry. The differences in outcome measures between the hormonal contraceptive groups will be analyzed in a one-way between-group analysis of covariance. Within the eumenorrheic group, the influence of the menstrual cycle on outcome measures will be assessed using a linear mixed effects model. Within the COCP group, differences across 2 time points will be analyzed using the paired-samples 2-tailed t test. RESULTS: The research was funded in January 2020, and data collection started in January 2022, with a projected data collection completion date of August 2024. The number of participants who have consented at the point of manuscript submission is 66. It is expected that all data analysis will be completed and results published by the end of 2024. CONCLUSIONS: Understanding the effects of the menstrual cycle and hormonal contraception on musculoskeletal health and performance will inform contraceptive choices for physically active women to manage injury risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT05587920; https://classic.clinicaltrials.gov/ct2/show/NCT05587920. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50542.

Effects of resistance exercise, collagen ingestion and circulating oestrogen concentration on collagen synthesis in a female athlete: A case report.

We investigated the effects of resistance exercise (RE), hydrolysed collagen (HC) ingestion and circulating oestrogen concentration on collagen synthesis in a naturally menstruating female CrossFit athlete. In a double-blind, randomised cross-over design, the participant (36 years; height 1.61 m; mass 82.6 kg) consumed 0 or 30 g HC prior to performing back-squat RE when endogenous circulating oestrogen concentration was low (onset of menses, OM) and high (late follicular phase, LF) during two consecutive menstrual cycles. Ten 5-mL blood samples were collected during each of the four interventions to analyse concentrations of serum 17ß-oestradiol, and biomarkers of type I collagen turnover, that is serum procollagen type I N-terminal propeptide (PINP, a biomarker of collagen synthesis) and plasma ß-isomerised C-terminal telopeptide of type I collagen (ß-CTX, a biomarker of collagen breakdown), as well as the serum concentration of 18 collagen amino acids. 17ß-Oestradiol concentration was 5-fold higher at LF (891 ± 116 pmol L-1) than OM (180 ± 13 pmol L-1). The PINP concentration × time area under the curve (AUC) was higher in the 30 g HC OM intervention (201 µg L-1 h) than the 30 g HC LF (144 µg L-1 h), 0 g HC OM (151 µg L-1 h) and 0 g HC LF (122 µg L-1 h) interventions. ß-CTX concentration decreased 1.4-fold from pre-RE to 6 h post-RE in all interventions. Thus, high circulating oestrogen concentration was associated with lower collagen synthesis following RE in this female athlete. Ingesting 30 g HC, however, augmented the collagen synthesis response at LF and particularly at OM. HIGHLIGHTS: What is the central question of this study? Does resistance exercise-induced collagen synthesis vary according to circulating oestrogen concentration in a naturally menstruating female athlete, and if so, does hydrolysed collagen ingestion have any impact? What is the main finding and its importance? Exercise-induced collagen synthesis was low when circulating oestrogen concentration was high and vice versa. However, ingesting 30 g hydrolysed collagen prior to exercise reduced the negative effect of oestrogen on collagen synthesis. As high circulating oestrogen has been associated with greater injury risk in females, supplementing exercise with hydrolysed collagen may help protect these tissues from injury.

Iron status is associated with tibial structure and vitamin D metabolites in healthy young men.

The influence of iron on collagen synthesis and vitamin D metabolism has implications for bone health. This cross-sectional observational study investigated associations between markers of iron status and tibial structure, vitamin D metabolites, and circulating biochemical markers of bone metabolism in young healthy men. A total of 343 male British Army recruits participated (age 22 ± 3 y, height 1.77 ± 0.06 m, body mass 75.5 ± 10.1 kg). Circulating biochemical markers of iron status, vitamin D metabolites, and bone metabolism, and tibial structure and density by high-resolution peripheral quantitative computed tomography scans (HRpQCT) were measured in participants during week 1 of basic military training. Associations between markers of iron status and HRpQCT outcomes, bone metabolism, and vitamin D metabolites were tested, controlling for age, height, lean body mass, and childhood exercise volume. Higher ferritin was associated with higher total, trabecular, and cortical volumetric bone mineral density, trabecular volume, cortical area and thickness, stiffness, and failure load (all p ≤ 0.037). Higher soluble transferrin receptor (sTfR) was associated with lower trabecular number, and higher trabecular thickness and separation, cortical thickness, and cortical pore diameter (all p ≤ 0.033). Higher haemoglobin was associated with higher cortical thickness (p = 0.043). Higher ferritin was associated with lower ßCTX, PINP, total 25(OH)D, and total 24,25(OH)2D, and higher 1,25(OH)2D:24,25(OH)2D ratio (all p ≤ 0.029). Higher sTfR was associated with higher PINP, total 25(OH)D, and total 24,25(OH)2D (all p ≤ 0.025). The greater density, size, and strength of the tibia, and lower circulating concentrations of markers of bone resorption and formation with better iron stores (higher ferritin) are likely as a result of the direct role of iron in collagen synthesis.

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation.

CONTEXT: Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation. OBJECTIVE AND METHODS: Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression. RESULTS: Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR. CONCLUSION: Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.

Comparative Study of Healthy Older and Younger Adults Shows They Have the Same Skin Concentration of Vitamin D3 Precursor, 7-Dehydrocholesterol, and Similar Response to UVR.

Vitamin D3 synthesis in human skin is initiated by solar ultraviolet radiation (UVR) exposure of precursor 7-dehydrocholesterol (7DHC), but influence of age on the early stage of vitamin D3 metabolism is uncertain. We performed a prospective standardised study in healthy ambulant adults aged ≥65 and ≤40 years examining (1) if baseline skin 7DHC concentration differs between younger and older adults and (2) the impact of older age on serum vitamin D3 response to solar simulated UVR. Eleven younger (18-40 years) and 10 older (65-89 years) adults, phototype I-III, received low-dose UVR (95% UVA, 5% UVB, 1.3 SED) to ~35% of the body surface area. Biopsies were taken for 7DHC assay from unexposed skin, skin immediately and 24 h post-UVR, and blood sampled at baseline, 24 h and 7 d post-UVR for vitamin D3 assay. Samples were analysed by HPLC-MS/MS. Baseline skin 7DHC (mean ± SD) was 0.22 ± 0.07 and 0.25 ± 0.08 µg/mg in younger versus older adults (no significant difference). Baseline serum vitamin D3 concentration was 1.5 ± 1.5 and 1.5 ± 1.7 nmol/L in younger versus older adults, respectively, and showed a significant increase in both groups post-UVR (no significant differences between age groups). Thus, skin 7DHC concentration was not a limiting factor for vitamin D3 production in older relative to younger adults. This information assists public health guidance on sun exposure/vitamin D nutrition, with particular relevance to the growing populations of healthy ambulant adults ≥65 years.

Influence of vitamin D supplementation on growth, body composition, pubertal development and spirometry in South African schoolchildren: a randomised controlled trial (ViDiKids).

OBJECTIVE: To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. DESIGN: Phase 3 double-blind randomised placebo-controlled trial. SETTING: Socioeconomically disadvantaged peri-urban district of Cape Town, South Africa. PARTICIPANTS: 1682 children of black African ancestry attending government primary schools and aged 6-11 years at baseline. INTERVENTIONS: Oral vitamin D3 (10 000 IU/week) versus placebo for 3 years. MAIN OUTCOME MEASURES: Height-for-age and body mass index-for-age, measured in all participants; Tanner scores for pubertal development, spirometric lung volumes and body composition, measured in a subset of 450 children who additionally took part in a nested substudy. RESULTS: Mean serum 25-hydroxyvitamin D3 concentration at 3-year follow-up was higher among children randomised to receive vitamin D versus placebo (104.3 vs 64.7 nmol/L, respectively; mean difference (MD) 39.7 nmol/L, 95% CI 37.6 to 41.9 nmol/L). No statistically significant differences in height-for-age z-score (adjusted MD (aMD) -0.08, 95% CI -0.19 to 0.03) or body mass index-for-age z-score (aMD -0.04, 95% CI -0.16 to 0.07) were seen between vitamin D versus placebo groups at follow-up. Among substudy participants, allocation to vitamin D versus placebo did not influence pubertal development scores, % predicted forced expiratory volume in 1 s (FEV1), % predicted forced vital capacity (FVC), % predicted FEV1/FVC, fat mass or fat-free mass. CONCLUSIONS: Weekly oral administration of 10 000 IU vitamin D3 boosted vitamin D status but did not influence growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02880982, South African National Clinical Trials Register DOH-27-0916-5527.

Influence of vitamin D supplementation on bone mineral content, bone turnover markers, and fracture risk in South African schoolchildren: multicenter double-blind randomized placebo-controlled trial (ViDiKids).

Randomized controlled trials (RCTs) to determine the influence of vitamin D on BMC and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n = 450) nested within a phase 3 RCT of weekly oral supplementation with 10 000 IU vitamin D3 vs placebo for 3 yr in HIV-uninfected Cape Town schoolchildren aged 6-11 yr. Outcomes were BMC at the whole body less head (WBLH) and LS and serum 25-hydroxyvitamin D3 (25(OH)D3), PTH, alkaline phosphatase, C-terminal telopeptide, and PINP. Incidence of fractures was a secondary outcome of the main trial (n = 1682). At baseline, mean serum 25(OH)D3 concentration was 70.0 nmol/L (SD 13.5), and 5.8% of participants had serum 25(OH)D3 concentrations <50 nmol/L. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI, 36.1 to 43.6) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI, -0.94 to -0.17). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI, -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI, -1.3 to 0.8) or serum concentrations of bone turnover markers. Fractures were rare among participants in the main trial randomized to vitamin D vs placebo (7/755 vs 10/758 attending at least 1 follow-up; adjusted odds ratio 0.70, 95% CI, 0.27 to 1.85). In conclusion, a 3-yr course of weekly oral vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC or serum concentrations of bone turnover markers. Fracture incidence was low, limiting power to detect an effect of vitamin D on this outcome.

Vitamin D­the "sunshine vitamin"­is essential for helping the body to absorb calcium from the diet, which is laid down in bone to improve its strength. There is a lack of clinical trials testing whether vitamin D supplements can improve bone content of calcium and other minerals, or reduce risk of bone fractures (broken bones) in children of Black African ancestry. We therefore conducted such a study, recruiting 1682 schoolchildren aged 6­11 yr living in Cape Town, South Africa. We found that a weekly dose of 10 000 international units (250 micrograms) of vitamin D3, given by mouth for 3 yr, was effective in boosting vitamin D levels in trial participants who received it. However, this did not have any effect on bone content of calcium and other minerals. Relatively few children experienced a broken bone during the study, so we were unable to say with confidence whether or not vitamin D supplements might affect this outcome.

Prenatal Exposure to Air Pollution and Respiratory Distress in Term Newborns: Results from the MIREC Prospective Pregnancy Cohort.

BACKGROUND: Respiratory distress is the leading cause of neonatal morbidity and mortality worldwide, and prenatal exposure to air pollution is associated with adverse long-term respiratory outcomes; however, the impact of prenatal air pollution exposure on neonatal respiratory distress has not been well studied. OBJECTIVES: We examined associations between prenatal exposures to fine particular matter (PM2.5) and nitrogen dioxide (NO2) with respiratory distress and related neonatal outcomes. METHODS: We used data from the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a prospective pregnancy cohort (n=2,001) recruited in the first trimester from 10 Canadian cities. Prenatal exposures to PM2.5 (n=1,321) and NO2 (n=1,064) were estimated using land-use regression and satellite-derived models coupled with ground-level monitoring and linked to participants based on residential location at birth. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between air pollution and physician-diagnosed respiratory distress in term neonates in hierarchical logistic regression models adjusting for detailed maternal and infant covariates. RESULTS: Approximately 7% of newborns experienced respiratory distress. Neonates received clinical interventions including oxygen therapy (6%), assisted ventilation (2%), and systemic antibiotics (3%). Two percent received multiple interventions and 4% were admitted to the neonatal intensive care unit (NICU). Median PM2.5 and NO2 concentrations during pregnancy were 8.81 µg/m3 and 18.02 ppb, respectively. Prenatal exposures to air pollution were not associated with physician-diagnosed respiratory distress, oxygen therapy, or NICU admissions. However, PM2.5 exposures were strongly associated with assisted ventilation (OR per 1-µg/m3 increase in PM2.5=1.17; 95% CI: 1.02, 1.35), multiple clinical interventions (OR per 1-µg/m3 increase in PM2.5=1.16; 95% CI: 1.07, 1.26), and systemic antibiotics, (OR per 1-µg/m3 increase in PM2.5=1.12; 95% CI: 1.04, 1.21). These associations were consistent across exposure periods-that is, during prepregnancy, individual trimesters, and total pregnancy-and robust to model specification. NO2 exposure was associated with administration of systemic antibiotics (OR per 1-ppb increase in NO2=1.03; 95% CI: 1.00, 1.06). DISCUSSION: Prenatal exposures to PM2.5 increased the risk of severe respiratory distress among term newborns. These findings support the development and prioritization of public health and prenatal care strategies to increase awareness and minimize prenatal exposures to air pollution. https://doi.org/10.1289/EHP12880.

Hormonal contraceptive use is associated with altered bone structural and metabolic responses to military training in women: An observational cohort study.

Military training increases tibial density and size. Female sex hormones may influence the adaption of bone to loading, but it is unknown if women using different hormonal contraceptives adapt similarly to military training. One hundred and sixteen women (57 women not using hormonal contraceptives [non-users], 38 combined oral contraceptive pill [COCP] users, 21 depot medroxyprogesterone acetate [DMPA] users) completed this study. Tibial volumetric bone mineral density (vBMD) and geometry were measured by peripheral quantitative computed tomography (4 %, 14 %, 38 %, and 66 % sites) at the start (week 1) and end (week 14) of British Army basic training. Circulating markers of bone and calcium metabolism were measured at weeks 1, 2, 4, 6, 10, and 14. Training increased trabecular vBMD at the 4 % site, periosteal perimeter at the 14 % and 66 % sites, and total area, cortical area, cortical thickness, and bone strength at all sites (0.1 to 1.6 %, p ≤ 0.009), with no differences between hormonal contraceptive groups (p ≥ 0.127). Trabecular vBMD increased at the 14 % site in non-users (0.8 %, p = 0.005), but not in COCP or DMPA users (p ≥ 0.205). Periosteal perimeter increased at the 38 % site in COCP (0.4 %, p < 0.001) and DMPA (0.5 %, p < 0.001) users, but not in non-users (p = 0.058). Training had no effect on periosteal perimeter at the 4 % site or cortical vBMD or endosteal perimeter at any site (p ≥ 0.168). ßCTX decreased and PINP increased during training with no difference between hormonal contraceptive groups. Training increased iPTH in non-users, but not COCP or DMPA users. Hormonal contraceptives may exert site-specific effects on the mechanobiology of bone, with higher endogenous oestradiol promoting trabecularisation and inhibiting periosteal expansion in non-users compared with hormonal contraceptive users.

Sex differences in iron status during military training: a prospective cohort study of longitudinal changes and associations with endurance performance and musculoskeletal outcomes.

This study investigated sex differences in Fe status, and associations between Fe status and endurance and musculoskeletal outcomes, in military training. In total, 2277 British Army trainees (581 women) participated. Fe markers and endurance performance (2·4 km run) were measured at the start (week 1) and end (week 13) of training. Whole-body areal body mineral density (aBMD) and markers of bone metabolism were measured at week 1. Injuries during training were recorded. Training decreased Hb in men and women (mean change (-0·1 (95 % CI -0·2, -0·0) and -0·7 (95 % CI -0·9, -0·6) g/dl, both P < 0·001) but more so in women (P < 0·001). Ferritin decreased in men and women (-27 (95 % CI -28, -23) and -5 (95 % CI -8, -1) µg/l, both P ≤ 0·001) but more so in men (P < 0·001). Soluble transferrin receptor increased in men and women (2·9 (95 % CI 2·3, 3·6) and 3·8 (95 % CI 2·7, 4·9) nmol/l, both P < 0·001), with no difference between sexes (P = 0·872). Erythrocyte distribution width increased in men (0·3 (95 % CI 0·2, 0·4)%, P < 0·001) but not in women (0·1 (95 % CI -0·1, 0·2)%, P = 0·956). Mean corpuscular volume decreased in men (-1·5 (95 % CI -1·8, -1·1) fL, P < 0·001) but not in women (0·4 (95 % CI -0·4, 1·3) fL, P = 0·087). Lower ferritin was associated with slower 2·4 km run time (P = 0·018), sustaining a lower limb overuse injury (P = 0·048), lower aBMD (P = 0·021) and higher beta C-telopeptide cross-links of type 1 collagen and procollagen type 1 N-terminal propeptide (both P < 0·001) controlling for sex. Improving Fe stores before training may protect Hb in women and improve endurance and protect against injury.

Collagen peptide supplementation before bedtime reduces sleep fragmentation and improves cognitive function in physically active males with sleep complaints.

PURPOSE: The primary aim of this study was to examine whether a glycine-rich collagen peptides (CP) supplement could enhance sleep quality in physically active men with self-reported sleep complaints. METHODS: In a randomized, crossover design, 13 athletic males (age: 24 ± 4 years; training volume; 7 ± 3 h·wk1) with sleep complaints (Athens Insomnia Scale, 9 ± 2) consumed CP (15 g·day1) or a placebo control (CON) 1 h before bedtime for 7 nights. Sleep quality was measured with subjective sleep diaries and actigraphy for 7 nights; polysomnographic sleep and core temperature were recorded on night 7. Cognition, inflammation, and endocrine function were measured on night 7 and the following morning. Subjective sleepiness and fatigue were measured on all 7 nights. The intervention trials were separated by ≥ 7 days and preceded by a 7-night familiarisation trial. RESULTS: Polysomnography showed less awakenings with CP than CON (21.3 ± 9.7 vs. 29.3 ± 13.8 counts, respectively; P = 0.028). The 7-day average for subjective awakenings were less with CP vs. CON (1.3 ± 1.5 vs. 1.9 ± 0.6 counts, respectively; P = 0.023). The proportion of correct responses on the baseline Stroop cognitive test were higher with CP than CON (1.00 ± 0.00 vs. 0.97 ± 0.05 AU, respectively; P = 0.009) the morning after night 7. There were no trial differences in core temperature, endocrine function, inflammation, subjective sleepiness, fatigue and sleep quality, or other measures of cognitive function or sleep (P > 0.05). CONCLUSION: CP supplementation did not influence sleep quantity, latency, or efficiency, but reduced awakenings and improved cognitive function in physically active males with sleep complaints.

Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget's disease of bone.

INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB. RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups. CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB. TRIAL REGISTRATION NUMBER: ISRCTN11616770.

Perinatal morbidity among women with a previous caesarean delivery (PRISMA trial): a cluster-randomised trial.

BACKGROUND: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery. METHODS: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559. FINDINGS: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups. INTERPRETATION: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture. FUNDING: Canadian Institutes of Health Research (CIHR, MOP-142448).

Cross-sectional study of the associations between circulating vitamin D concentrations and insulin resistance in children aged 9-10 years of South Asian, black African Caribbean and white European origins.

BACKGROUND: Lower circulating vitamin D 25-hydroxyvitamin D (25(OH)D) concentrations are associated with higher type 2 diabetes risk in adults, although causality remains uncertain. However, associations between 25(OH)D and type 2 diabetes risk markers in children have been little studied, particularly in ethnic minority populations. We examined whether 25(OH)D concentrations were associated with insulin resistance in children and whether lower 25(OH)D concentrations in South Asians and black African Caribbeans could contribute to their higher insulin resistance. METHODS: Cross-sectional study of 4650 UK primary school children aged 9-10 years of predominantly South Asian, black African Caribbean and white European ethnicity. Children had fasting blood measurements of circulating 25(OH)D metabolite concentrations, insulin and glucose. RESULTS: Lower 25(OH)D concentrations were observed in girls, South Asians and black African Caribbeans. In analyses adjusted for age, sex, month, ethnic group and school, circulating 25(OH)D was inversely associated with fasting insulin (-0.38%, 95% CI -0.49% to -0.27%), homoeostasis model assessment (HOMA) insulin resistance (-0.39%, 95% CI -0.50% to -0.28%) and fasting glucose (-0.03%, 95% CI -0.05% to -0.02%) per nmol/L increase in 25(OH)D; associations did not differ between ethnic groups. Ethnic differences in fasting insulin and HOMA insulin resistance (higher among South Asian and black African Caribbeans) were reduced by >40% after adjustment for circulating 25(OH)D concentrations. CONCLUSION: Circulating vitamin D was inversely associated with insulin resistance in all ethnic groups; higher insulin resistance in South Asian and black African children were partly explained by their lower vitamin D levels. Whether vitamin D supplementation can reduce emerging type 2 diabetes risk needs further evaluation.

Cohort profile update: The Canadian Maternal-Infant Research on Environmental Chemicals Child Development study (MIREC-CD PLUS).

BACKGROUND: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. OBJECTIVES: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. POPULATION: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. PRELIMINARY RESULTS: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). CONCLUSIONS: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development.

Second-trimester abortion and risk of live birth.

BACKGROUND: Second-trimester abortion may result in a live birth, but the extent to which this outcome occurs is unknown. OBJECTIVE: This study aimed to examine rates of live birth after pregnancy termination in the second trimester and identify associated risk factors. STUDY DESIGN: We conducted a retrospective cohort study of 13,777 second-trimester abortions occurring in hospital settings between April 1, 1989 and March 31, 2021 in Quebec, Canada. The exposure was induced abortion between 15 and 29 weeks of gestation, including the indication for (fetal anomaly, maternal emergency, other) and use of feticidal injection (intracardiac/intrathoracic or intraamniotic). The primary outcome was live birth following abortion. We measured the rate of live birth per 100 abortions and used adjusted log-binomial regression models to estimate risk ratios and 95% confidence intervals for the association of fetal and maternal characteristics with the risk of live birth. We assessed the extent to which feticidal injection reduced the risk. RESULTS: Among 13,777 abortions between 15 and 29 weeks of gestation, 1541 (11.2%) led to live birth. Fetal anomaly was a common indication for termination (48.1%), and most abortions were by labor induction (72.2%). Compared with abortion between 15 and 19 weeks, abortion between 20 and 24 weeks was associated with 4.80 times the risk of live birth (95% confidence interval, 4.20-5.48), whereas abortion between 25 and 29 weeks was associated with 1.34 times the risk (95% confidence interval, 1.00-1.79). Feticidal injection reduced the risk of live birth by 57% compared with no injection (risk ratio, 0.43; 95% confidence interval, 0.36-0.51). Intracardiac or intrathoracic injection was particularly effective at preventing live birth (risk ratio, 0.02; 95% confidence interval, 0.01-0.07). CONCLUSION: Second-trimester abortion carries a risk of live birth, especially at 20 to 24 weeks of gestation, although feticidal injection may protect against this outcome.

Longitudinal associations between paternal mental health and child behavior and cognition in middle childhood.

Introduction: Paternal mental health has been associated with adverse consequences on offspring psychosocial development, and family environmental factors may partly explain those associations. To clarify this, we need comprehensive prospective studies, particularly in middle-childhood when the child enters school and is expected to make use of behavioral and cognitive skills as part of their interactions and learning. Method: Using data from a sub-sample of the prospective 3D birth cohort study comprised of mother-father-child triads, and a follow-up of the parents and the children at 6-8 years of age (n = 61; 36 boys, 25 girls), we examined whether paternal anxious and depressive symptoms measured during the pregnancy period (i.e., prenatally) or concurrently when the child was assessed at 6-8 years old were associated with children's cognition/behavior. Results: In contrast to our hypotheses, we found that greater prenatal paternal depressive symptoms predicted fewer child behavioral difficulties; and that greater concurrent childhood paternal depression or anxiety symptoms were associated with higher child full-scale IQ, controlling for the equivalent maternal mental health assessment and parental education. Father parenting perception did not mediate these associations, nor were they moderated by maternal mental health at the concurrent assessment, or paternal ratings of marital relationship quality. Discussion: These findings suggest that higher symptoms of paternal mental health symptoms are associated with fewer child behavioral difficulties and higher cognitive performance in middle childhood. Potential clinical implications and future research directions are discussed.