Wearable-derived maternal heart rate variability as a novel digital biomarker of preterm birth.

Despite considerable health consequences from preterm births, their incidence remains unchanged over recent decades, due partially to limited screening methods and limited use of extant methods. Wearable technology offers a novel, noninvasive, and acceptable way to track vital signs, such as maternal heart rate variability (mHRV). Previous research observed that mHRV declines throughout the first 33 weeks of gestation in term, singleton pregnancies, after which it improves. The aim of this study was to explore whether mHRV inflection is a feature of gestational age or an indication of time to delivery. This retrospective case-control study considered term and preterm deliveries. Remote data collection via non-invasive wearable technology enabled diverse participation with subjects representing 42 US states and 16 countries. Participants (N = 241) were retroactively identified from the WHOOP (Whoop, Inc.) userbase and wore WHOOP straps during singleton pregnancies between March 2021 and October 2022. Mixed effect spline models by gestational age and time until birth were fit for within-person mHRV, grouped into preterm and term births. For term pregnancies, gestational age (Akaike information criterion (AIC) = 26627.6, R2m = 0.0109, R2c = 0.8571) and weeks until birth (AIC = 26616.3, R2m = 0.0112, R2c = 0.8576) were representative of mHRV trends, with significantly stronger fit for weeks until birth (relative log-likelihood ratio = 279.5). For preterm pregnancies, gestational age (AIC = 1861.9, R2m = 0.0016, R2c = 0.8582) and time until birth (AIC = 1848.0, R2m = 0.0100, R2c = 0.8676) were representative of mHRV trends, with significantly stronger fit for weeks until birth (relative log-likelihood ratio = 859.4). This study suggests that wearable technology, such as the WHOOP strap, may provide a digital biomarker for preterm delivery by screening for changes in nighttime mHRV throughout pregnancy that could in turn alert to the need for further evaluation and intervention.

Connection Between Sleep and Psychological Well-Being in U.S. Army Soldiers.

INTRODUCTION: The goal of this exploratory study was to examine the relationships between sleep consistency and workplace resilience among soldiers stationed in a challenging Arctic environment. MATERIALS AND METHODS: A total of 862 soldiers (67 females) on an Army base in Anchorage, AK, were provided WHOOP 3.0, a validated sleep biometric capture device and were surveyed at onboarding and at the conclusion of the study. Soldiers joined the study from early January to early March 2021 and completed the study in July 2021 (650 soldiers completed the onboarding survey and 210 completed the exit survey, with 151 soldiers completing both). Three comparative analyses were conducted. First, soldiers' sleep and cardiac metrics were compared against the general WHOOP population and a WHOOP sample living in AK. Second, seasonal trends (summer versus winter) in soldiers' sleep metrics (time in bed, hours of sleep, wake duration during sleep, time of sleep onset/offset, and disturbances) were analyzed, and these seasonal trends were compared with the general WHOOP population and the WHOOP sample living in AK. Third, soldiers' exertion, sleep duration, and sleep consistency were correlated with their self-reported psychological functioning. All analyses were conducted with parametric and non-parametric statistics. This study was approved by The University of Queensland Human Research Ethics Committee (Brisbane, Australia) Institutional Review Board. RESULTS: Because of the exploratory nature of the study, the critical significance value was set at P < .001. Results revealed that: (1) Arctic soldiers had poorer sleep consistency and sleep duration than the general WHOOP sample and the Alaskan WHOOP sample, (2) Arctic soldiers showed a decrease in sleep consistency and sleep duration in the summer compared to that in the winter, (3) Arctic soldiers were less able to control their bedroom environment in the summer than in the winter, and (4) sleep consistency but not sleep duration correlated positively with self-report measures of workplace resilience and healthy social networks and negatively with homesickness. CONCLUSIONS: The study highlights the relationship between seasonality, sleep consistency, and psychological well-being. The results indicate the potential importance of sleep consistency in psychological functioning, suggesting that future work should manipulate factors known to increase sleep consistency to assess whether improved sleep consistency can enhance the well-being of soldiers. Such efforts would be of particular value in an Arctic environment, where seasonality effects are large and sleep consistency is difficult to maintain.

Pre-sleep feeding, sleep quality, and markers of recovery in division I NCAA female soccer players.

Pre-sleep nutrition habits in elite female athletes have yet to be evaluated. A retrospective analysis was performed with 14 NCAA Division I female soccer players who wore a WHOOP, Inc. band - a wearable device that quantifies recovery by measuring sleep, activity, and heart rate metrics through actigraphy and photoplethysmography, respectively - 24 h a day for an entire competitive season to measure sleep and recovery. Pre-sleep food consumption data were collected via surveys every 3 days. Average pre-sleep nutritional intake (mean ± sd: kcals 330 ± 284; cho 46.2 ± 40.5 g; pro 7.6 ± 7.3 g; fat 12 ± 10.5 g) was recorded. Macronutrients and kcals were grouped into high and low categories based upon the 50th percentile of the mean to compare the impact of a high versus low pre-sleep intake on sleep and recovery variables. Sleep duration (p = 0.10, 0.69, 0.16, 0.17) and sleep disturbances (p = 0.42, 0.65, 0.81, 0.81) were not affected by high versus low kcal, PRO, fat, CHO intake, respectively. Recovery (p = 0.81, 0.06, 0.81, 0.92), RHR (p = 0.84, 0.64, 0.26, 0.66), or HRV (p = 0.84, 0.70, 0.76, 0.93) were also not affected by high versus low kcal, PRO, fat, or CHO consumption, respectively. Consuming a small meal before bed may have no impact on sleep or recovery.

Wearable derived cardiovascular responses to stressors in free-living conditions.

Stress contributes to the progression of many diseases. Despite stress' contribution towards disease, few methods for continuously measuring stress exist. We investigated if continuously measured cardiovascular signals from a wearable device can be used as markers of stress. Using wearable technology (WHOOP Inc, Boston, MA) that continuously measures and calculates heart rate (HR) and heart rate variability (root-mean-square of successive differences; HRV), we assessed duration and magnitude of deviations in HR and HRV around the time of a run (from 23665 runs) or high-stress work (from 8928 high-stress work events) in free-living conditions. HR and HRV were assessed only when participants were motionless (HRmotionless). Runs were grouped into light, moderate, and vigorous runs to determine dose response relationships. When examining HRmotionless and HRV throughout the day, we found that these metrics display circadian rhythms; therefore, we normalized HRmotionless and HRV measures for each participant relative to the time of day. Relative to the period within 30 minutes leading up to a run, HRmotionless is elevated for up to 180-210 minutes following a moderate or vigorous run (P<0.05) and is unchanged or reduced following a light run. HRV is reduced for at least 300 minutes following a moderate or vigorous run (P<0.05) and is unchanged during a light run. Relative to the period within 30 minutes leading up to high-stress work, HRmotionless is elevated during and for up to 30 minutes following high-stress work. HRV tends to be lower during high-stress work (P = 0.06) and is significantly lower 90-300 minutes after the end of the activity (P<0.05). These results demonstrate that wearables can quantify stressful events, which may be used to provide feedback to help individuals manage stress.

Neonatal intake of Omega-3 fatty acids enhances lipid oxidation in adipocyte precursors.

Establishing metabolic programming begins during fetal and postnatal development, and early-life lipid exposures play a critical role during neonatal adipogenesis. We define how neonatal consumption of a low omega-6 to -3 fatty acid ratio (n6/n3 FA ratio) establishes FA oxidation in adipocyte precursor cells (APCs) before they become adipocytes. In vivo, APCs isolated from mouse pups exposed to the low n6/n3 FA ratio had superior FA oxidation capacity, elevated beige adipocyte mRNAs Ppargc1α, Ucp2, and Runx1, and increased nuclear receptor NR2F2 protein. In vitro, APC treatment with NR2F2 ligand-induced beige adipocyte mRNAs and increased mitochondrial potential but not mass. Single-cell RNA-sequencing analysis revealed low n6/n3 FA ratio yielded more mitochondrial-high APCs and linked APC NR2F2 levels with beige adipocyte signatures and FA oxidation. Establishing beige adipogenesis is of clinical relevance, because fat depots with energetically active, smaller, and more numerous adipocytes improve metabolism and delay metabolic dysfunction.

Biometrics from a wearable device reveal temporary effects of COVID-19 vaccines on cardiovascular, respiratory, and sleep physiology.

Although vaccines against SARS-CoV-2 have been proven safe and effective, transient side-effects lasting 24-48 h postvaccination have been reported. To better understand the subjective and objective response to COVID-19 vaccination, we conducted a retrospective analysis on 69,619 subscribers to a wrist-worn biometric device (WHOOP Inc., Boston, MA) who received either the AstraZeneca, Janssen/Johnson & Johnson, Moderna, or Pfizer/BioNTech vaccine. The WHOOP device measures resting heart rate (RHR), heart rate variability (HRV), respiratory rate (RR), and sleep architecture, and these physiological measures were normalized to the same day of the week, 1 wk before vaccination. Averaging across vaccines, RHR, RR, and percent sleep derived from light sleep were elevated on the first night following vaccination and returned to baseline within 4 nights postvaccination. When statistical differences were observed between doses on the first night postvaccination, larger deviations in physiological measures were observed following the first dose of AstraZeneca and the second dose of Moderna and Pfizer/BioNTech. When statistical differences were observed between age groups or gender on the first night postvaccination, larger deviations in physiological measures were observed in younger populations and in females (compared with males). When combining self-reported symptoms (fatigue, muscle aches, headache, chills, or fever) with the objectively measured physiological parameters, we found that self-reporting fever or chills had the strongest association with deviations in physiological measures following vaccination. In summary, these results suggest that COVID-19 vaccines temporarily affect cardiovascular, respiratory, and sleep physiology and that dose, gender, and age affect the physiological response to vaccination.NEW & NOTEWORTHY Here we report the first large-scale study investigating the effect of COVID-19 vaccines on cardiovascular, respiratory, and sleep physiology. We find that vaccines temporarily impact measures of cardiovascular, respiratory, and sleep physiology and that the degree of change in physiology is influenced by the manufacturer and dose of the vaccine and the gender and age of the vaccine recipient. These results provide insights into physiological changes that occur with COVID-19 vaccination and indicate that the unique responses that occur postvaccination may depend on manufacturer, dose, gender, and age.

Lipoprotein Lipase Overexpression in Skeletal Muscle Attenuates Weight Regain by Potentiating Energy Expenditure.

Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain.

Sex differences in the effect of diet, obesity, and exercise on bone quality and fracture toughness.

Bone fragility and obesity are both diseases that are multifactorial in etiology and pathology. The contributing role of high fat diet (HFD) versus energy overconsumption on bone health is controversial. Exercise is often prescribed for improving bone health, but it is unclear whether HFD or overconsumption influences skeletal adaptations to exercise. Female and male Wistar rats were fed HFD or low fat diet (LFD) for 10 weeks, starting at 8 weeks of age. Within HFD, rats were labeled Obesity-Resistant (OR) or Obesity-Prone (OP) based on weight and fat gain. Within each diet and phenotype group, rats were randomized to treadmill exercise or sedentary control (SED) for the final 4 weeks. Femurs were assessed for fracture toughness. Cortical lamellar and nonlamellar bone microscale material behavior and chemistry were assessed using nanoindentation and Raman spectroscopy. Female bones had higher fracture toughness and mineral: matrix ratio than male bones. Diet and energy overconsumption affected bone characteristics in a sex-dependent manner, where the divergence between OP and OR in response to HFD occurred more rapidly in males. Diet composition, in general, had a stronger effect on bone quality than overconsumption. HFD dramatically decreased bone size and lamellar mineral:matrix compared to LFD. Effects of short-term exercise training on microscale tissue properties were generally more robust with LFD. Exercise enhanced the contrast between lamellar and nonlamellar bone for nanoindentation modulus but decreased this contrast for plastic work. Our data demonstrate the complexities in the relationship between diet and obesity and highlight the importance of addressing both aspects when characterizing bone quality and fracture resistance.

Compensatory eating behaviors in male and female rats in response to exercise training.

Exercise is often used as a strategy for weight loss maintenance. In preclinical models, we have shown that exercise may be beneficial because it counters the biological drive to regain weight. However, our studies have demonstrated sex differences in the response to exercise in this context. In the present study, we sought to better understand why females and males exhibit different compensatory food eating behaviors in response to regular exercise. Using a forced treadmill exercise paradigm, we measured weight gain, energy expenditure, food intake in real time, and the anorectic effects of leptin. The 4-wk exercise training resulted in reduced weight gain in males and sustained weight gain in females. In male rats, exercise decreased intake, whereas it increased food intake in females. Our results suggest that the anorectic effects of leptin were not responsible for these sex differences in appetite in response to exercise. If these results translate to the human condition, they may reveal important information for the use and application of regular exercise programs.

Regular exercise potentiates energetically expensive hepatic de novo lipogenesis during early weight regain.

Exercise is a potent facilitator of long-term weight loss maintenance (WLM), whereby it decreases appetite and increases energy expenditure beyond the cost of the exercise bout. We have previously shown that exercise may amplify energy expenditure through energetically expensive nutrient deposition. Therefore, we investigated the effect of exercise on hepatic de novo lipogenesis (DNL) during WLM and relapse to obesity. Obese rats were calorically restricted with (EX) or without (SED) treadmill exercise (1 h/day, 6 days/wk, 15 m/min) to induce and maintain weight loss. After 6 wk of WLM, subsets of WLM-SED and WLM-EX rats were allowed ad libitum access to food for 1 day to promote relapse (REL). An energy gap-matched group of sedentary, relapsing rats (REL-GM) were provided a diet matched to the positive energy imbalance of the REL-EX rats. During relapse, exercise increased enrichment of hepatic DN-derived lipids and induced hepatic molecular adaptations favoring DNL compared with the gap-matched controls. In the liver, compared with both REL-SED and REL-GM rats, REL-EX rats had lower hepatic expression of genes required for cholesterol biosynthesis; greater hepatic expression of genes that mediate very low-density lipoprotein synthesis and secretion; and greater mRNA expression of Cyp27a1, which encodes an enzyme involved in the biosynthesis of bile acids. Altogether, these data provide compelling evidence that the liver has an active role in exercise-mediated potentiation of energy expenditure during early relapse.

Impact of Exercise and Activity on Weight Regain and Musculoskeletal Health Post-Ovariectomy.

The purpose of this study was to determine whether obesity and/or exercise training alters weight regain and musculoskeletal health after ovariectomy (OVX). Female rats were fed high-fat diet (HFD) to reveal obesity-prone (OP) and obesity-resistant (OR) phenotypes. The OP and OR exercising (EX) and sedentary (SED) rats were calorically restricted to lose 15% of body weight using medium-fat diet. Rats were then maintained in energy balance for 8 wk before OVX. After OVX and a brief calorically limited phase, rats were allowed to eat ad libitum until body weight plateaued. Starting at weight loss, EX ran 1 h·d, 6 d·wk, 15 m·min. Energy intake, spontaneous physical activity (SPA), and total energy expenditure were evaluated at the end of weight maintenance pre-OVX, and at three time points post-OVX: before weight regain, during early regain, and after regain. Data are presented as mean ± SE. Exercise attenuated weight regain after OVX in OP only (OP-EX, 123 ± 10 g; OP-SED, 165 ± 12 g; OR-EX, 121 ± 6 g; OR-SED, 116 ± 6 g), which was primarily an attenuation of fat gain. The early post-OVX increase in energy intake explained much of the weight regain, and was similar across groups. Exercising improved bone strength, as did maintaining SPA. Group differences in muscle mitochondrial respiration were not significant. The large decrease in SPA due to OVX was persistent, but early weight regain was dependent on decreased SPA. In conclusion, leanness and exercise do not necessarily protect from OVX-induced weight gain. Exercise prevented weight gain in obese rats, but loss of SPA was the greatest contributor to post-OVX weight gain. Thus, understanding the mechanisms resulting in reduction in SPA after ovarian hormone loss is critical in the prevention of menopause-associated metabolic dysfunction.

Compensation for cold-induced thermogenesis during weight loss maintenance and regain.

Prevalence of obesity is exacerbated by low rates of successful long-term weight loss maintenance (WLM). In part, relapse from WLM to obesity is due to a reduction in energy expenditure (EE) that persists throughout WLM and relapse. Thus, interventions that increase EE might facilitate WLM. In obese mice that were calorically restricted to reduce body weight by ~20%, we manipulated EE throughout WLM and early relapse using intermittent cold exposure (ICE; 4°C, 90 min/day, 5 days/wk, within the last 3 h of the light cycle). EE, energy intake, and spontaneous physical activity were measured during the obese, WLM, and relapse phases. During WLM and relapse, the ICE group expended more energy during the light cycle because of cold exposure but expended less energy in the dark cycle, which led to no overall difference in total daily EE. The compensation in EE appeared to be mediated by activity, whereby the ICE group was more active during the light cycle because of cold exposure but less active during the dark cycle, which led to no overall effect on total daily activity during WLM and relapse. In brown adipose tissue of relapsing mice, the ICE group had greater mRNA expression of Dio2 and protein expression of UCP1 but lower mRNA expression of Prdm16. In summary, these findings indicate that despite robust increases in EE during cold exposures, ICE is unable to alter total daily EE during WLM or early relapse, likely due to compensatory behaviors in activity.

Low Neonatal Plasma n-6/n-3 PUFA Ratios Regulate Offspring Adipogenic Potential and Condition Adult Obesity Resistance.

Adipose tissue expansion progresses rapidly during postnatal life, influenced by both prenatal maternal factors and postnatal developmental cues. The ratio of omega-6 (n-6) relative to n-3 polyunsaturated fatty acids (PUFAs) is believed to regulate perinatal adipogenesis, but the cellular mechanisms and long-term effects are not well understood. We lowered the fetal and postnatal n-6/n-3 PUFA ratio exposure in wild-type offspring under standard maternal dietary fat amounts to test the effects of low n-6/n-3 ratios on offspring adipogenesis and adipogenic potential. Relative to wild-type pups receiving high perinatal n-6/n-3 ratios, subcutaneous adipose tissue in 14-day-old wild-type pups receiving low n-6/n-3 ratios had more adipocytes that were smaller in size; decreased Pparγ2, Fabp4, and Plin1; several lipid metabolism mRNAs; coincident hypermethylation of the PPARγ2 proximal promoter; and elevated circulating adiponectin. As adults, offspring that received low perinatal n-6/n-3 ratios were diet-induced obesity (DIO) resistant and had a lower positive energy balance and energy intake, greater lipid fuel preference and non-resting energy expenditure, one-half the body fat, and better glucose clearance. Together, the findings support a model in which low early-life n-6/n-3 ratios remodel adipose morphology to increase circulating adiponectin, resulting in a persistent adult phenotype with improved metabolic flexibility that prevents DIO.

Prior weight loss exacerbates the biological drive to gain weight after the loss of ovarian function.

Both the history of obesity and weight loss may change how menopause affects metabolic health. The purpose was to determine whether obesity and/or weight loss status alters energy balance (EB) and subsequent weight gain after the loss of ovarian function. Female lean and obese Wistar rats were randomized to 15% weight loss (WL) or ad libitum fed controls (CON). After the weight loss period, WL rats were kept in EB at the reduced weight for 8 weeks prior to ovariectomy (OVX). After OVX, all rats were allowed to eat ad libitum until weight plateaued. Energy intake (EI), spontaneous physical activity, and total energy expenditure (TEE) were measured with indirect calorimetry before OVX, immediately after OVX, and after weight plateau. Changes in energy intake (EI), TEE, and weight gain immediately after OVX were similar between lean and obese rats. However, obese rats gained more total weight and fat mass than lean rats over the full regain period. Post-OVX, EI increased more (P ≤ 0.03) in WL rats (58.9 ± 3.5 kcal/d) than CON rats (8.5 ± 5.2 kcal/d), and EI partially normalized (change from preOVX: 20.5 ± 4.2 vs. 1.5 ± 4.9 kcal/day) by the end of the study. As a result, WL rats gained weight (week 1:44 ± 20 vs. 7 ± 25 g) more rapidly (mean = 44 ± 20 vs. 7 ± 25 g/week; P < 0.001) than CON Prior obesity did not affect changes in EB or weight regain following OVX, whereas a history of weight loss prior to OVX augmented disruptions in EB after OVX, resulting in more rapid weight regain.