Consistent cord blood DNA methylation signatures of gestational age between South Asian and white European cohorts.

BACKGROUND: Epigenetic modifications, particularly DNA methylation (DNAm) in cord blood, are an important biological marker of how external exposures during gestation can influence the in-utero environment and subsequent offspring development. Despite the recognized importance of DNAm during gestation, comparative studies to determine the consistency of these epigenetic signals across different ethnic groups are largely absent. To address this gap, we first performed epigenome-wide association studies (EWAS) of gestational age (GA) using newborn cord blood DNAm comparatively in a white European (n = 342) and a South Asian (n = 490) birth cohort living in Canada. Then, we capitalized on established cord blood epigenetic GA clocks to examine the associations between maternal exposures, offspring characteristics and epigenetic GA, as well as GA acceleration, defined as the residual difference between epigenetic and chronological GA at birth. RESULTS: Individual EWASs confirmed 1,211 and 1,543 differentially methylated CpGs previously reported to be associated with GA, in white European and South Asian cohorts, respectively, with a similar distribution of effects. We confirmed that Bohlin's cord blood GA clock was robustly correlated with GA in white Europeans (r = 0.71; p = 6.0 × 10-54) and South Asians (r = 0.66; p = 6.9 × 10-64). In both cohorts, Bohlin's clock was positively associated with newborn weight and length and negatively associated with parity, newborn female sex, and gestational diabetes. Exclusive to South Asians, the GA clock was positively associated with the newborn ponderal index, while pre-pregnancy weight and gestational weight gain were strongly predictive of increased epigenetic GA in white Europeans. Important predictors of GA acceleration included gestational diabetes mellitus, newborn sex, and parity in both cohorts. CONCLUSIONS: These results demonstrate the consistent DNAm signatures of GA and the utility of Bohlin's GA clock across the two populations. Although the overall pattern of DNAm is similar, its connections with the mother's environment and the baby's anthropometrics can differ between the two groups. Further research is needed to understand these unique relationships.

The association of red and processed meat with gestational diabetes mellitus: Results from 2 Canadian birth cohort studies.

OBJECTIVE: Red and processed meat is considered risk factors of gestational diabetes mellitus (GDM), but the evidence is inconclusive. We aimed to examine the association between red and processed meat intake and odds of GDM among South Asian and White European women living in Canada. METHODS: This is a cross-sectional analysis of pregnant women from two birth cohorts: SouTh Asian biRth cohorT (START; n = 976) and Family Atherosclerosis Monitoring In earLY life (FAMILY; n = 581). Dietary intake was assessed using a validated 169-item semi-quantitative food-frequency questionnaire (FFQ). Multivariate logistic regression models were used to examine the associations between gestational diabetes and: 1) total red and processed meat; 2) unprocessed red meat; 3) processed meat and GDM after adjustment for potential confounders. RESULTS: There were 241 GDM cases in START and 91 in FAMILY. The median total red and processed meat intake were 1.5 g/d (START) and 52.8 g/d (FAMILY). In START, the multivariable-adjusted odds ratio (OR) showed neither lower nor higher intakes of unprocessed red meat (p-trend = 0.68), processed meat (p-trend = 0.90), or total red and processed meat (p-trend = 0.44), were associated with increased odds of GDM, when compared with medium intake. Similar results were observed in FAMILY except for processed meat intake [OR = 0.94 (95% CI 0.47-1.91), for medium versus low and OR = 1.51 (95% CI 0.77-2.29) for medium versus high; p-trend = 0.18] after adjusting for additional dietary factors such as the diet quality score, total fiber, saturated fat and glycemic load. CONCLUSION: Medium compared with low or high red and processed meat intake is not associated with GDM in White Europeans and South Asians living in Canada.

Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.

PURPOSE: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome. METHODS: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4). RESULTS: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001). CONCLUSION: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity.

Association between impaired lung function and carotid intima-media thickness in children.

Association between obstructive lung function impairment with higher cIMT is present in childhood after accounting for common risk factors. This suggests that a developmental link between obstructive lung diseases and CVD may have its origin in early life. https://bit.ly/4657s2b.

Parity modulates impact of BMI and gestational weight gain on gut microbiota in human pregnancy.

Dysregulation of maternal adaptations to pregnancy due to high pre-pregnancy BMI (pBMI) or excess gestational weight gain (GWG) is associated with worsened health outcomes for mothers and children. Whether the gut microbiome contributes to these adaptations is unclear. We longitudinally investigated the impact of pBMI and GWG on the pregnant gut microbiome. We show that the gut microbiota of participants with higher pBMI changed less over the course of pregnancy in primiparous but not multiparous participants. This suggests that previous pregnancies may have persistent impacts on maternal adaptations to pregnancy. This ecological memory appears to be passed on to the next generation, as parity modulated the impact of maternal GWG on the infant gut microbiome. This work supports a role of the gut microbiome in maternal adaptations to pregnancy and highlights the need for longitudinal sampling and accounting for parity as key considerations for studies of the microbiome in pregnancy and infants. Understanding how these factors contribute to and shape maternal health is essential for the development of interventions impacting the microbiome, including pre/probiotics.

Early neurodevelopment in the offspring of women enrolled in a randomized controlled trial assessing the effectiveness of a nutrition + exercise intervention on the cognitive development of 12-month-olds.

Experimental data on the effects of lifestyle interventions on fetal neurodevelopment in humans remain scarce. This study assessed the impact of a pregnancy nutrition+exercise intervention on offspring neurodevelopment at 12 months of age. The Be Healthy in Pregnancy (BHIP) randomized controlled trial (RCT) randomly assigned pregnant persons with stratification by site and body mass index (BMI) to bi-weekly nutrition counselling and high dairy protein diet, walking goal of 10,000 steps/day plus usual prenatal care (UPC; intervention group) or UPC alone (control group). This study examined a subset of these mothers (> 18 years, singleton pregnancy, BMI <40 kg/m2, and enrolled by ≤12 weeks gestation) and their infants (intervention = 42, control = 32), assessing cognition, language, motor, social-emotional, and adaptive functioning at 12 months using the Bayley Scales of Infant and Toddler Development third edition (BSID-III) as the outcome measure. We also examined if maternal factors (prepregnancy BMI, gestational weight gain (GWG)) moderated associations. Expressive language (MD = 9.62, 95% CI = (9.05-10.18), p = 0.03, ƞ2p = 0.07) and general adaptive composite (GAC) scores (MD = 103.97, 95% CI = (100.31-107.63), p = 0.04, ƞ2p = 0.06) were higher in infants of mothers in the intervention group. Effect sizes were medium. However, mean cognitive, receptive language, motor, and social-emotional scale scores did not differ between groups. A structured and monitored nutrition+exercise intervention during pregnancy led to improved expressive language and general adaptive behavior in 12-month-olds, but not cognitive, receptive language, motor, or socioemotional functioning. While these experimental data are promising, further research is needed to determine the clinical utility of nutrition+exercise interventions for optimizing infant neurodevelopment.

Comparative Assessment of Diet Quality and Adherence to a Structured Nutrition and Exercise Intervention Compared with Usual Care in Pregnancy in a Randomized Trial.

Background: In trials testing the efficacy of diet and exercise modifications during pregnancy on health outcomes, assessment of participant adherence to interventions of diet and exercise is rarely reported, with few standard methods existing to measure adherence. Objective: We aimed to assess the maternal diet quality and create an algorithm to evaluate adherence to an intervention of high protein/dairy nutrition and walking exercise from early pregnancy to birth. Methods: In Be Healthy in Pregnancy randomized trial (NCT01693510), diet quality was measured using scores from an adapted PrimeScreen food frequency questionnaire, nutrient intake assessed by 3-day diet records, and physical activity using accelerometry at 14-17 (early), 26-28 (middle), and 36-38 (late) weeks' gestation. A novel adherence score was derived by combining data for compliance with prescribed protein and energy intakes and daily step counts in the intervention group. Between-group diet quality scores and changes in adherence scores in the intervention group across pregnancy were analyzed using generalized estimating equations adjusted for prepregnancy body mass index and study site. Results: Diet scores were similar for intervention (n = 55) and control (n = 56) groups at baseline but only the intervention group significantly improved and maintained their scores from early to middle (18.7 ± 7.6 vs. 22.9 ± 6.1; P < 0.001) and late (22.5 ± 6.9; P < 0.008) pregnancy. Protein intake was significantly (P < 0.001) higher but energy intakes were similar in the intervention group compared with those in the control group. Adherence scores for the intervention increased significantly (P < 0.01) from early (1.52 ± 0.70) to midpregnancy (1.89 ± 0.82) but declined from midpregnancy to late (1.55 ± 0.78; P < 0.0005) pregnancy primarily owing to lower step counts. Conclusions: Adherence to an intervention may decline toward the end of pregnancy, particularly in maintaining physical activity. Creation of adherence scores is a feasible approach to measure combined intervention compliance for diet and physical activity and may increase transparency in interpreting results of randomized trials in pregnancy.This trial was registered at clinicaltrials.gov as NCT01689961 (https://clinicaltrials.gov/ct2/show/NCT01689961?cond=NCT01689961&rank=1; registered on 21 September 2012).

Reductions in Bone Mineral Density Are Apparent Early in Children With Prevalent Osteonecrosis Lesions Following Leukemia Therapy.

Osteonecrosis (ON) is a serious complication of childhood acute lymphoblastic leukemia. We determined the prevalence of osteonecrotic lesions in our patient population by a one-time multisite magnetic resonance imaging (MRI) more than 1 year following leukemia therapy. MRI findings were evaluated in relationship to clinical factors (including longitudinal changes in bone mineral density [BMD]). Eighty-six children enrolled in the Steroid Associated Osteoporosis in the Pediatric Population (STOPP) study were evaluated for ON at 3.1 ± 1.3 years following therapy. Thirty children had a total of 150 confirmed ON lesions (35%). Lumbar spine (LS) BMD Z-scores (mean ± SD) were low at diagnosis and similar between patients with and without ON (-1.09 ± 1.53 versus -1.27 ± 1.25, p = 0.549). LS BMD Z-scores declined from baseline to 12 months in children with ON (-0.31 ± 1.02) but not in those without (0.13 ± 0.82, p = 0.035); the hip BMD Z-scores from baseline to 24 months declined in both groups, but to a greater extent in those with ON (-1.77 ± 1.22) compared to those without (-1.03 ± 1.07, p = 0.045). At the time of the MRI, mean total hip and total body (TB) BMD Z-scores were lower in children with ON (hip -0.98 ± 0.95 versus -0.28 ± 1.06, p = 0.010; TB -1.36 ± 1.10 versus -0.48 ± 1.50, p = 0.018). Pain occurred in 11/30 (37%) with ON versus 20/56 (36%) without, p = 0.841. In multivariable models, older age at diagnosis (odds ratio [OR] 1.57; 95% confidence interval [CI], 1.15-2.13; p = 0.004), and hip BMD Z-score at MRI (OR 2.23; 95% CI, 1.02-4.87; p = 0.046) were independently associated with ON. Overall, one-third of children demonstrated ON after leukemia therapy. Those with ON had greater reductions in spine and hip BMD Z-scores in the first 1 and 2 years of therapy, respectively. Older age and lower hip BMD Z-scores at MRI were significantly associated with prevalent, off-therapy ON. These data assist in identifying children at risk of ON. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Early sex-dependent differences in metabolic profiles of overweight and adiposity in young children: a cross-sectional analysis.

BACKGROUND: Childhood obesity is a global health concern and can lead to lifetime cardiometabolic disease. New advances in metabolomics can provide biochemical insights into the early development of obesity, so we aimed to characterize serum metabolites associated with overweight and adiposity in early childhood and to stratify associations by sex. METHODS: Nontargeted metabolite profiling was conducted in the Canadian CHILD birth cohort (discovery cohort) at age 5 years (n = 900) by multisegment injection-capillary electrophoresis-mass spectrometry. Clinical outcome was defined using novel combined measures of overweight (WHO-standardized body mass index ≥ 85th percentile) and/or adiposity (waist circumference ≥ 90th percentile). Associations between circulating metabolites and child overweight/adiposity (binary and continuous outcomes) were determined by multivariable linear and logistic regression, adjusting for covariates and false discovery rate, and by subsequent sex-stratified analysis. Replication was assessed in an independent replication cohort called FAMILY at age 5 years (n = 456). RESULTS: In the discovery cohort, each standard deviation (SD) increment of branched-chain and aromatic amino acids, glutamic acid, threonine, and oxoproline was associated with 20-28% increased odds of overweight/adiposity, whereas each SD increment of the glutamine/glutamic acid ratio was associated with 20% decreased odds. All associations were significant in females but not in males in sex-stratified analyses, except for oxoproline that was not significant in either subgroup. Similar outcomes were confirmed in the replication cohort, where associations of aromatic amino acids, leucine, glutamic acid, and the glutamine/glutamic acid ratio with childhood overweight/adiposity were independently replicated. CONCLUSIONS: Our findings show the utility of combining measures of both overweight and adiposity in young children. Childhood overweight/adiposity at age 5 years has a specific serum metabolic phenotype, with the profile being more prominent in females compared to males.

Prevalence of sarcopenia indicators and sub-optimal protein intake among elective total joint replacement patients.

Sarcopenia is associated with falls, and can complicate recovery following total joint replacement (TJR) surgery. We examined (1) the prevalence of sarcopenia indicators and lower-than-recommended protein intake among TJR patients and non-TJR community participants and (2) the relationships between dietary protein intake and sarcopenia indicators. We recruited adults ≥65 years of age who were undergoing TJR, and adults from the community not undergoing TJR (controls). We assessed grip strength and appendicular lean soft-tissue mass (ALSTMBMI) using DXA, and applied the original Foundation for the National Institutes of Health Sarcopenia Project cut-points for sarcopenia indicators (grip strength <26 kg for men and <16 kg for women; ALSTM <0.789 m2 for men and <0.512 m2 for women) and less conservative cut-points (grip strength <31.83 kg for men and <19.99 kg for women; ALSTM <0.725 m2 for men and <0.591 m2 for women). Total daily and per meal protein intakes were derived from 5-day diet records. Sixty-seven participants (30 TJR, 37 controls) were enrolled. Using less conservative cut-points for sarcopenia, more control participants were weak compared with TJR participants (46% versus 23%, p = 0.055), and more TJR participants had low ALSTMBMI (40% versus 13%, p = 0.013). Approximately 70% of controls and 76% of TJR participants consumed <1.2 g protein/kg/day (p = 0.559). Total daily dietary protein intake was positively associated with grip strength (r = 0.44, p = 0.001) and ALSTMBMI (r = 0.29, p = 0.03). Using less conservative cut-points, low ALSTMBMI, but not weakness, was more common in TJR patients. Both groups may benefit from a dietary intervention to increase protein intake, which may improve surgical outcomes in TJR patients.

A harmonized analysis of five Canadian pregnancy cohort studies: exploring the characteristics and pregnancy outcomes associated with prenatal alcohol exposure.

BACKGROUND: As a teratogen, alcohol exposure during pregnancy can impact fetal development and result in adverse birth outcomes. Despite the clinical and social importance of prenatal alcohol use, limited routinely collected information or epidemiological data exists in Canada. The aim of this study was to pool data from multiple Canadian cohort studies to identify sociodemographic characteristics before and during pregnancy that were associated with alcohol consumption during pregnancy and to assess the impact of different patterns of alcohol use on birth outcomes. METHODS: We harmonized information collected (e.g., pregnant women's alcohol intake, infants' gestational age and birth weight) from five Canadian pregnancy cohort studies to consolidate a large sample (n = 11,448). Risk factors for any alcohol use during pregnancy, including any alcohol use prior to pregnancy recognition, and binge drinking, were estimated using binomial regressions including fixed effects of pregnancy cohort membership and multiple maternal risk factors. Impacts of alcohol use during pregnancy on birth outcomes (preterm birth and low birth weight for gestational) were also estimated using binomial regression models. RESULTS: In analyses adjusting for multiple risk factors, women's alcohol use during pregnancy, both any use and any binge drinking, was associated with drinking prior to pregnancy, smoking during pregnancy, and white ethnicity. Higher income level was associated with any drinking during pregnancy. Neither drinking during pregnancy nor binge drinking during pregnancy was significantly associated with preterm delivery or low birth weight for gestational age in our sample. CONCLUSIONS: Pooling data across pregnancy cohort studies allowed us to create a large sample of Canadian women and investigate the risk factors for alcohol consumption during pregnancy. We suggest that future pregnancy and birth cohorts should always include questions related to the frequency and amount of alcohol consumed before and during pregnancy that are prospectively harmonized to support data reusability and collaborative research.

Preliminary findings of emotion regulation in 12-month-old infants of mothers enrolled in a randomized controlled trial assessing a nutrition + exercise intervention.

Improved offspring emotion regulation (ER) has been associated with maternal intake of single nutrients or exercise during pregnancy but has not been examined in randomized trials. We investigated the impact of a maternal nutrition + exercise intervention during pregnancy on offspring ER at 12 months of age. Mothers in the Be Healthy In Pregnancy randomized controlled trial were randomly assigned to an individualized nutrition + exercise intervention plus usual care (UC) or UC alone (control group). A multimethod assessment of infant ER using parasympathetic nervous system function (high frequency heart rate variability [HF-HRV] and root mean square of successive differences [RMSSD]) as well as maternal reports of infant temperament (Infant Behavior Questionnaire- Revised short form) was completed with a subsample of infants of enrolled mothers (intervention = 9, control = 8). The trial was registered at www.clinicaltrials.gov (NCT01689961). We observed greater HF-HRV (M = 4.63, SD = 0.50, p = .04, ƞ2 p  = .25) and RMSSD (M = 24.25, SD = 6.15, p = .04, ƞ2 p  = .25) in infants of mothers in the intervention versus control group. Intervention group infants also had higher maternally rated surgency/extraversion (M = 5.54, SD = 0.38, p = .00, ƞ2 p  = .65) and regulation/orienting (M = 5.46, SD = 0.52, p = .02, ƞ2 p  = .81), and lower negative affectivity (M = 2.70, SD = 0.91, p = .03, ƞ2 p  = .52). These preliminary results suggest that pregnancy nutrition + exercise interventions could improve infant ER but these findings require replication in larger, more diverse samples.

Dynamic Metabolic Signatures of Choline and Carnitine across Healthy Pregnancy and in Cord Blood: Association with Maternal Dietary Protein.

BACKGROUND: In pregnancy, choline is deemed an essential nutrient and carnitine needs are increased, but amounts remain undefined. OBJECTIVES: We aimed to measure choline and total dietary protein and dairy protein intake from food and supplements across pregnancy and the response to intake by profiling choline and carnitine metabolites across pregnancy and in cord blood. METHODS: An exploratory analysis of choline and protein intake from 3-d diet records and measures of 36 serum choline and carnitine metabolites in early (12-17 wk) and late (36-38 wk) pregnancy was conducted in participants from the Be Healthy in Pregnancy study randomized to high dairy protein+walking exercise or usual care. Metabolites were measured in fasted maternal and cord serum using multisegment injection-capillary electrophoresis-mass spectrometry. Mixed ANOVA adjusted for body mass index was performed for comparison of metabolites across pregnancy and between intervention and control. RESULTS: In 104 participants, the median (Q1, Q3) total choline intake was 347 (263, 427) mg/d in early and 322 (270, 437) mg/d in late pregnancy. Only ∼20% of participants achieved the recommended adequate intake (450 mg/d) and ∼10% consumed supplemental choline (8-200 mg/d). Serum-free choline (µmol/L) was higher in late compared with early pregnancy [12.9 (11.4, 15.1) compared with 9.68 (8.25, 10.61), P < 0.001], but choline downstream metabolites were similar across pregnancy. Serum carnitine [10.3 (9.01, 12.2) compared with 15.9 (14.1, 17.9) µmol/L, P < 0.001] and acetylcarnitine [2.35 (1.92, 2.68) compared with 3.0 (2.56, 3.59), P < 0.001] were significantly lower in late pregnancy. High cord:maternal serum metabolite ratios were found in most measured metabolites. CONCLUSIONS: Despite inadequate choline intake, serum-free choline was elevated in late pregnancy and enriched in cord blood compared with maternal serum. Serum carnitine declined in late pregnancy despite a high protein diet. The higher cord:maternal concentrations in choline and carnitine metabolites suggest active uptake in late pregnancy, reflecting the importance of these circulating metabolites in fetal development. This trial was registered at clinicaltrials.gov as NCT01689961.

Medical, behavioural and social preconception and interconception risk factors among pregnancy planning and recently pregnant Canadian women.

OBJECTIVES: The objective of this study is to describe the clustering of medical, behavioural and social preconception and interconception health risk factors and determine demographic factors associated with these risk clusters among Canadian women. DESIGN: Cross-sectional data were collected via an online questionnaire assessing a range of preconception risk factors. Prevalence of each risk factor and the total number of risk factors present was calculated. Multivariable logistic regression models determined which demographic factors were associated with having greater than the mean number of risk factors. Exploratory factor analysis determined how risk factors clustered, and Spearman's r determined how demographic characteristics related to risk factors within each cluster. SETTING: Canada. PARTICIPANTS: Participants were recruited via advertisements on public health websites, social media, parenting webpages and referrals from ongoing studies or existing research datasets. Women were eligible to participate if they could read and understand English, were able to access a telephone or the internet, and were either planning a first pregnancy (preconception) or had ≥1 child in the past 5 years and were thus in the interconception period. RESULTS: Most women (n=1080) were 34 or older, and were in the interconception period (98%). Most reported risks in only one of the 12 possible risk factor categories (55%), but women reported on average 4 risks each. Common risks were a history of caesarean section (33.1%), miscarriage (27.2%) and high birth weight (13.5%). Just over 40% had fair or poor eating habits, and nearly half were not getting enough physical activity. Three-quarters had a body mass index indicating overweight or obesity. Those without a postsecondary degree (OR 2.35; 95% CI 1.74 to 3.17) and single women (OR 2.22, 95% CI 1.25 to 3.96) had over twice the odds of having more risk factors. Those with two children or more had 60% lower odds of having more risk factors (OR 0.68, 95% CI 0.52 to 0.86). Low education and being born outside Canada were correlated with the greatest number of risk clusters. CONCLUSIONS: Many of the common risk factors were behavioural and thus preventable. Understanding which groups of women are prone to certain risk behaviours provides opportunities for researchers and policy-makers to target interventions more efficiently and effectively.

Individualized high dairy protein + walking program supports bone health in pregnancy: a randomized controlled trial.

BACKGROUND: Pregnancy induces bone mineral mobilization, which may be further compromised if diet and physical activity are suboptimal. OBJECTIVES: We aimed to determine the effects of a Nutrition + Exercise intervention during pregnancy on maternal calciotropic and bone biomarker profiles throughout pregnancy and the postpartum. METHODS: In the Be Healthy in Pregnancy (BHIP) randomized controlled trial, 203 of 225 participants who consented to the bone health substudy were, randomly assigned at 12-17 weeks gestation to receive either usual care (control) or a structured and monitored Nutrition + Exercise plan (intervention) providing an individualized high dairy protein diet and a walking program throughout pregnancy. Maternal serum total procollagen type 1 N-terminal propeptide (P1NP; bone formation), C-terminal telopeptide of type I collagen (CTX; bone resorption), and insulin-like growth factor-1 (IGF-1) were measured by ELISA, and vitamin D metabolites by ultra-performance LC tandem MS at early and late pregnancy, 6 mo postpartum, and in cord blood. RESULTS: In 187 participants completing all measures, significantly higher intakes were observed in the intervention than in the control group for total protein (P < 0.0001), protein intake from dairy foods (P < 0.0001), and calcium (P < 0.0001), whereas vitamin D intake was similar between treatment groups in both the second and third trimesters. The intervention group had significantly lower serum CTX at end of pregnancy (mean ± SD: 0.78 ± 0.31 ng/mL; n = 91 compared with 0.89 ± 0.33 ng/mL; n = 96, P = 0.034) and in cord serum (0.58 ± 0.13 ng/mL; n = 31 compared with 0.69 ± 0.18 ng/mL; n = 22, P < 0.025). Serum concentrations of P1NP rose significantly (P < 0.02) from early pregnancy to 6 mo postpartum for the intervention group only. Serum 25-hydroxyvitamin D status was >50 nmol/L for 97% of all participants. CONCLUSIONS: Higher maternal dietary protein and calcium intakes than usual care in concert with normal vitamin D status minimized bone resorption and maintained bone formation and may protect bone health during pregnancy.This trial was registered at clinicaltrials.gov as NCT01689961.

Sources of Variation in Food-Related Metabolites during Pregnancy.

The extent to which variation in food-related metabolites are attributable to non-dietary factors remains unclear, which may explain inconsistent food-metabolite associations observed in population studies. This study examined the association between non-dietary factors and the serum concentrations of food-related biomarkers and quantified the amount of variability in metabolite concentrations explained by non-dietary factors. Pregnant women (n = 600) from two Canadian birth cohorts completed a validated semi-quantitative food frequency questionnaire, and serum metabolites were measured by multisegment injection-capillary electrophoresis-mass spectrometry. Hierarchical linear modelling and principal component partial R-square (PC-PR2) were used for data analysis. For proline betaine and DHA (mainly exogenous), citrus foods and fish/fish oil intake, respectively, explained the highest proportion of variability relative to non-dietary factors. The unique contribution of dietary factors was similar (15:0, 17:0, hippuric acid, TMAO) or lower (14:0, tryptophan betaine, 3-methylhistidine, carnitine) compared to non-dietary factors (i.e., ethnicity, maternal age, gestational age, pre-pregnancy BMI, physical activity, and smoking) for metabolites that can either be produced endogenously, biotransformed by gut microbiota, and/or derived from multiple food sources. The results emphasize the importance of adjusting for non-dietary factors in future analyses to improve the accuracy and precision of the measures of food intake and their associations with health and disease.

Exploring comparative assessment of adiposity measures during pregnancy and postpartum.

BACKGROUND & AIMS: Excessive adiposity in pregnancy is associated with an altered cardiometabolic profile and adverse maternal and offspring outcomes. Pre-pregnancy body mass index (pBMI) is a proxy measure for adiposity that is most often used in clinical settings; however, it may not identify at-risk pregnancies caused by adiposity-related cardiometabolic dysfunction. The challenge is that validated direct adiposity measures are limited due to the dynamic nature of pregnancy. This exploratory analysis aimed to, 1) evaluate longitudinal changes in % body fat (BF) and the agreement between skinfold thickness (SFT) and bioelectrical impedance analysis (BIA) across pregnancy and in postpartum; 2) compare the discrimination power of SFT, BIA, and pBMI regarding adiposity status; and 3) assess agreement between SFT and BIA with dual-energy X-ray absorptiometry (DXA) in the postpartum. METHODS: Participants enrolled in the Be Healthy in Pregnancy (BHIP) RCT (NCT01693510) had demographic data and pBMI collected at enrollment and adiposity measured at 12-17, 26-28, and 36-38 weeks gestation by BIA (%BF) and SFT (sum and %BF), and also by DXA at 6 months postpartum. Agreement between methods was assessed by Bland Altman plots and McNemar's test and C-statistic for discriminative power. RESULTS: In 181 women with mean pBMI of 25.1 kg/m2 (min: 17.4 kg/m2, max: 39.6 kg/m2) and age 31.6 (SD: 4.0 yr), maternal adiposity increased significantly (p < 0.001) across pregnancy when measured by the sum of SFT or %BF by BIA, but not %BF by SFT. In early pregnancy, BF by BIA and SFT showed good agreement, with BIA values 1.8% greater than SFT, but low agreement in late pregnancy, with BIA values 7.1% greater than SFT. However, in the postpartum, agreement was similar to early pregnancy, and both BIA and SFT demonstrated good agreement with DXA. By pBMI, 45.5% of participants were categorized as overweight/obese, compared to 66.5% by BIA (p < 0.0001) and 54.5% by SFT (p < 0.0001). CONCLUSIONS: In comparison to SFT and BIA, the results suggest that pBMI is less sensitive in identifying participants with excessive adiposity, limiting its use as a screening tool for adiposity-related adverse outcomes in pregnancy. It would be preferable to use a direct measure of adiposity to screen for at-risk pregnancies. Both %BF by BIA and sum of SFT can quantify the change in adiposity across pregnancy and in the postpartum and thus could be adopted as clinical practice tools. Future research efforts should further refine and validate adiposity techniques for use, particularly in mid and late pregnancy. CLINICAL TRIAL: The BHIP clinical trial (NCT01693510). REGISTRATION SITE: https://clinicaltrials.gov/ct2/show/NCT01693510.

Serum metabolomic signatures of gestational diabetes in South Asian and white European women.

INTRODUCTION: This study aimed to identify serum metabolomic signatures associated with gestational diabetes mellitus (GDM), and to examine if ethnic-specific differences exist between South Asian and white European women. RESEARCH DESIGN AND METHODS: Prospective cohort study with a nested case-control analysis of 600 pregnant women from two Canadian birth cohorts; using an untargeted approach, 63 fasting serum metabolites were measured and analyzed using multisegment injection-capillary electrophoresis-mass spectrometry. Multivariate logistic regression modeling was conducted overall and by cohort. RESULTS: The proportion of women with GDM was higher in South Asians (27.1%) compared with white Europeans (17.9%). Several amino acid, carbohydrate, and lipid pathways related to GDM were common to South Asian and white European women. Elevated circulating concentrations of glutamic acid, propionylcarnitine, tryptophan, arginine, 2-hydroxybutyric acid, 3-hydroxybutyric acid, and 3-methyl-2-oxovaleric acid were associated with higher odds of GDM, while higher glutamine, ornithine, oxoproline, cystine, glycine with lower odds of GDM. Per SD increase in glucose concentration, the odds of GDM increased (OR=2.07, 95% CI 1.58 to 2.71), similarly for metabolite ratios: glucose to glutamine (OR=2.15, 95% CI 1.65 to 2.80), glucose to creatinine (OR=1.79, 95% CI 1.39 to 2.32), and glutamic acid to glutamine (OR=1.46, 95% CI 1.16 to 1.83). South Asians had higher circulating ratios of glucose to glutamine, glucose to creatinine, arginine to ornithine, and citrulline to ornithine, compared with white Europeans. CONCLUSIONS: We identified a panel of serum metabolites implicated in GDM pathophysiology, consistent in South Asian and white European women. The metabolic alterations leading to larger ratios of glucose to glutamine, glucose to creatinine, arginine to ornithine, and citrulline to ornithine in South Asians likely reflect the greater burden of GDM among South Asians compared with white Europeans.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) I-Cognitive Function and Metabolic Risk.

Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, n = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; p = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, n = 438; aRR 0.94 [0.76, 1.17]; p = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, n = 1406; aRR 0.76 [0.60, 0.97]; p = 0.03), and improved motor scores overall (13 trials, n = 1406; adjusted mean difference 1.57 [0.14, 2.99]; p = 0.03) and in girls not boys (p = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.

How Do Health Schemas Inform Healthy Behaviours During Pregnancy? Qualitative Findings from the Be Healthy in Pregnancy (BHIP) Study.

OBJECTIVE: Excess gestational weight gain (GWG) is associated with adverse long and short-term outcomes for both woman and child, yet evidence demonstrates pregnant women are frequently not engaging in healthy behaviours linked to appropriate weight gain. The purpose of the current study was to explore women's values and beliefs related to weight, nutrition and physical activity during pregnancy and to describe how these beliefs influence their behaviours. METHODS: As part of a larger randomized controlled trial, we conducted 20 focus groups with 66 pregnant women between 16 and 24-weeks gestation using a semi-structured interview guide. Focus groups were recorded and transcribed verbatim and analyzed using a grounded theory approach. RESULTS: Three personal health schemas emerged from the findings which illustrated women's diverging beliefs about their health behaviours in pregnancy. 'Interconnected health' described beliefs regarding the impact their health had on that of their growing baby and awareness of risks associated with inappropriate weight gain. 'Gestational weight gain as an indicator of health' illustrated perceptions regarding how GWG impacted health and the utility of guidelines. Finally, 'Control in pregnancy' described the sense of agency over one's body and health. CONCLUSIONS FOR PRACTICE: Our results showed that health-related behaviours in pregnancy are driven by personal health schemas which are often discordant with clinical evidence. Interventions and health care provider advice aimed at behaviour modification would benefit from first understanding and addressing these schemas. Tackling the conflict between beliefs and behaviour may improve health outcomes associated with appropriate weight gain in pregnancy.