Cardiovascular disease hospitalizations among women who undergo fertility treatment.

RESEARCH QUESTION: Are women who receive fertility treatment at increased risk of cardiovascular disease (CVD) hospitalization compared with women who do not? DESIGN: A retrospective cohort study of all women registered for fertility treatment at Monash IVF between 1998 and 2014. This cohort was linked to the Victorian Admitted Episodes Dataset, which contains records of all hospital admissions in the Australian state of Victoria. Age- and Index of Relative Socioeconomic Disadvantage (IRSD)-adjusted relative risks of CVD hospitalization for women who did or did not undergo fertility treatment were determined using Poisson regression. Risks were calculated overall by CVD subtype and stratified by area-based social disadvantage using IRSD fifths, number of stimulated cycles and mean oocytes per cycle. RESULTS: Of 27,262 women registered for fertility treatment, 24,131 underwent treatment and 3131 did not. No significant difference was found in risk of CVD hospitalization between treated and untreated women overall (adjusted RR 0.93, 95% 0.82 to 1.05) or by CVD subtype. The admission risk for CVD was significantly lower in treated women who had a mean of fewer than five oocytes per cycle (adjusted RR 0.80, 95% CI 0.70 to 0.92) compared with untreated women. Treated women residing in areas within the second IRSD fifth were less likely to be hospitalized for CVD compared with untreated women (age-adjusted RR 0.66, 95% CI 0.49 to 0.89). CONCLUSIONS: Fertility treatment is not associated with increased risk of CVD hospitalization. Lower risk among some subgroups of treated women may be explained by social disadvantage.

Short apneas and periodic breathing in preterm infants in the neonatal intensive care unit-Effects of sleep position, sleep state, and age.

This observational study investigated the effects of sleep position and sleep state on short apneas and periodic breathing in hospitalized preterm infants longitudinally, in relation to postmenstrual age. Preterm infants (25-31 weeks gestation, n = 29) were studied fortnightly after birth until discharge, in prone and supine positions, and in quiet sleep and active sleep. The percentage of time spent in each sleep state (percentage of time in quiet sleep and percentage of time in active sleep), percentage of total sleep time spent in short apneas and periodic breathing, respectively, the percentage of falls from baseline in heart rate, arterial oxygen saturation and cerebral tissue oxygenation index during short apneas and periodic breathing, and the associated percentage of total sleep time with systemic (arterial oxygen saturation < 90%) and cerebral hypoxia (cerebral tissue oxygenation index < 55%) were analysed using a linear mixed model. Results showed that the prone position decreased (improved) the percentage of falls from baseline in arterial oxygen saturation during both short apneas and periodic breathing, decreased the proportion of infants with periodic breathing and the periodic breathing-associated percentage of total sleep time with cerebral hypoxia. The percentage of time in quiet sleep was higher in the prone position. Quiet sleep decreased the percentage of total sleep time spent in short apneas, the short apneas-associated percentage of falls from baseline in heart rate, arterial oxygen saturation, and proportion of infants with systemic hypoxia. Quiet sleep also decreased the proportion of infants with periodic breathing and percentage of total sleep time with cerebral hypoxia. The effects of sleep position and sleep state were not related to postmenstrual age. In summary, when sleep state is controlled for, the prone sleeping position has some benefits during both short apneas and periodic breathing. Quiet sleep improves cardiorespiratory stability and is increased in the prone position at the expense of active sleep, which is critical for brain maturation. This evidence should be considered in positioning preterm infants.

The association between sleep duration and muscle sympathetic nerve activity.

PURPOSE: Sleep duration is associated with risk of hypertension and cardiovascular diseases. It is thought that shorter sleep increases sympathetic activity. However, most studies are based on acute experimental sleep deprivation that have produced conflicting results. Furthermore, there are limited data available on habitual sleep duration and gold-standard measures of sympathetic activation. Hence, this study aimed to assess the association between habitual sleep duration and muscle sympathetic nerve activity. METHODS: Twenty-four participants aged ≥ 18 years were included in the study. Sleep was assessed using at-home 7-day/night actigraphy (ActiGraph™ GT3X-BT) and sleep questionnaires (Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale). Microelectrode recordings of muscle sympathetic nerve activity were obtained from the common peroneal nerve. Participants were categorised into shorter or longer sleep duration groups using a median split of self-report and actigraphy sleep measures. RESULTS: Compared to longer sleepers, shorter sleepers averaged 99 ± 40 min and 82 ± 40 min less sleep per night as assessed by self-report and objective measures, respectively. There were no differences in age (38 ± 18 vs 39 ± 21 years), sex (5 male, 7 female vs 6 male, 6 female), or body mass index (23 ± 3 vs 22 ± 3 kg/m2) between shorter and longer sleepers. Expressed as burst frequency, muscle sympathetic nerve activity was higher in shorter versus longer sleepers for both self-report (39.4 ± 12.9 vs 28.4 ± 8.5 bursts/min, p = 0.019) and objective (37.9 ± 12.4 vs 28.1 ± 8.8 bursts/min, p = 0.036) sleep duration. CONCLUSIONS: Shorter sleep duration assessed in a home setting was associated with higher muscle sympathetic nerve activity. Sympathetic overactivity may underlie the association between short sleep and hypertension.

Long term all-cause and cardiovascular disease mortality among women who undergo fertility treatment.

OBJECTIVES: To compare age-adjusted all-cause and CVD mortality, relative to the general female population, for women registered for fertility treatment who received it and those who did not. DESIGN: Prospective cohort study; analysis of Monash IVF clinical registries data, 1975-2018, linked with National Death Index mortality data. PARTICIPANTS: All women who registered for fertility treatment at Monash IVF (Melbourne, Victoria), 1 January 1975 - 1 January 2014, followed until 31 December 2018. MAIN OUTCOME MEASURES: Standardised mortality ratios (SMRs) for all-cause and CVD mortality, for women who did or did not undergo fertility treatment; SMRs stratified by area-level socio-economic disadvantage (SEIFA Index of Relative Socioeconomic Disadvantage [IRSD]) and (for women who underwent treatment), by stimulated cycle number and mean oocytes/cycle categories. RESULTS: Of 44 149 women registered for fertility treatment, 33 520 underwent treatment (66.4%), 10 629 did not. After adjustment for age, both all-cause (SMR, 0.58; 95% CI, 0.54-0.62) and CVD mortality (SMR, 0.41; 95% CI, 0.32-0.53) were lower than for the general female population. All-cause mortality was similar for women registered with Monash IVF who did (SMR, 0.55; 95% CI, 0.50-0.60) or did not undergo fertility treatment (SMR, 0.63; 95% CI, 0.56-0.70). The SMR was lowest for both treated and untreated women in the fifth IRSD quintile (least disadvantage), but the difference was statistically significant only for untreated women. CVD mortality was lower for registered women who underwent fertility treatment (SMR, 0.29; 95% CI, 0.19-0.43) than for those who did not (SMR, 0.58; 95% CI, 0.42-0.81). CONCLUSION: Fertility treatment does not increase long term all-cause or CVD mortality risk. Lower mortality among women registered for fertility treatment probably reflected their lower socio-economic disadvantage.

Prone sleeping affects cardiovascular control in preterm infants in NICU.

BACKGROUND: Prone sleeping is used in preterm infants undergoing intensive care to improve respiratory function, but evidence suggests that this position may compromise autonomic cardiovascular control. To test this hypothesis, this study assessed the effects of the prone sleeping position on cardiovascular control in preterm infants undergoing intensive care treatment during early postnatal life. METHODS: Fifty-six preterm infants, divided into extremely preterm (gestational age (GA) 24-28 weeks, n = 23) and very preterm (GA 29-34 weeks, n = 33) groups, were studied weekly for 3 weeks in prone and supine positions, during quiet and active sleep. Heart rate (HR) and non-invasive blood pressure (BP) were recorded and autonomic measures of HR variability (HRV), BP variability (BPV), and baroreflex sensitivity (BRS) using frequency analysis in low (LF) and high (HF) bands were assessed. RESULTS: During the first 3 weeks, prone sleeping increased HR, reduced BRS, and increased HF BPV compared to supine. LF and HF HRV were also lower prone compared to supine in very preterm infants. Extremely preterm infants had the lowest HRV and BRS measures, and the highest HF BPV. CONCLUSIONS: Prone sleeping dampens cardiovascular control in early postnatal life in preterm infants, having potential implications for BP regulation in infants undergoing intensive care.

Improved sleep efficiency is associated with reduced cardio-metabolic risk: Findings from the MODERN trial.

Poor sleep increases cardio-metabolic risk, but limited information on the impact of sleep for the improvement of cardio-metabolic health exists. This analysis examined the impact of sleep on a health and lifestyle modification programme to reduce cardio-metabolic disease risk factors. Secondary analysis of the MODERN randomised controlled trial to reduce cardio-metabolic risk was undertaken at baseline and 24-month follow-up. Participants aged 40-70 years (n = 121) with three or more cardio-metabolic risk factors were randomised to a health and lifestyle modification intervention (n = 59) or usual care (n = 62), and underwent 7 day/night actigraphy to assess total sleep time, sleep efficiency (%), number of awakenings/night and physical activity levels. Blood pressure, blood lipid and glycaemic levels, anthropometric and diet measures were collected. The mean age was 59 ± 7 years and 37% were male. Baseline sleep measures were not different between groups. At the 24-month follow-up, both groups showed improvements in cardio-metabolic risk factors, albeit the change in blood pressure was greater in the intervention compared with the usual care group (systolic blood pressure: -11 versus -4 mmHg, p = .014). There were no differences between groups for diet, physical activity or sleep parameters. An increase in sleep efficiency was independently associated with lower systolic blood pressure (ß = -2.117, p = .002) and higher high-density lipoprotein levels (ß = 0.040, p = .033); an increase in total sleep time was associated with lower low-density lipoprotein levels (ß = -0.003, p = .038) at 24 months. Overall, improvement in sleep quality over time was beneficial to reduce blood pressure and lipid levels. These findings highlight sleep as a potential target to reduce cardio-metabolic risk.

Sleep quantity and quality and cardiometabolic risk factors in Indigenous Australians.

Poor sleep is associated with increased risk of cardiovascular disease (CVD). Indigenous Australians have 1.3 times higher risk of CVD compared to non-indigenous Australians. However, there are limited data describing sleep problems and cardiometabolic risk in this population. This study aimed to investigate sleep quantity and quality in indigenous Australians and assess its association with cardiometabolic risk. Two hundred and forty-five indigenous Australians aged > 18 years were recruited via convenience sampling from communities in the Northern Territory and Queensland. Sleep quantity and quality was assessed subjectively with questionnaires including the Epworth Sleepiness Scale. In a sub-population (n = 46), objective sleep assessment was performed over three nights of actigraphy. Cardiometabolic risk measures included glycated haemoglobin, lipids, anthropometric measurements and sitting blood pressure. Sleep duration measured subjectively and objectively averaged 7.5 ± 2.0 hr/night; however, over one-third of participants (self-report 35%; actigraphy 39%) obtained < 7 hr/night. Overall, more than a third of participants experienced poor-quality sleep, with 27% reporting severe daytime sleepiness (ESS score > 10) and a high number of objectively measured awakenings/night (6 ± 4). Short sleep duration (<6 hr/night) measured both subjectively and objectively was an independent predictor of diastolic (ß = 5.37, p = .038) and systolic blood pressure (ß = 14.30, p = .048). More objectively measured night-time awakenings were associated with increased glycated haemoglobin levels (ß = 0.07, p = .020) and greater sleep fragmentation was associated with lower high-density lipoprotein levels (ß = -0.01, p = .025). A large proportion of indigenous Australians experienced short sleep durations and had significant sleep disruption. Poor sleep quantity and quality may contribute to heightened cardiometabolic risk in this population.

Imaging-guided evaluation of subclinical atherosclerosis to enhance cardiovascular risk prediction in asymptomatic low-to-intermediate risk individuals: A systematic review.

Carotid intima-media thickness (cIMT), plaque quantification and coronary artery calcium (CAC) scoring have been suggested to improve risk prediction of cardiovascular disease (CVD), particularly for asymptomatic individuals classified as low-to-intermediate risk. We aimed to compare the predictive value of cIMT, carotid plaque identification, and CAC scoring for identifying sub-clinical atherosclerosis and assessing future risk of CVD in asymptomatic, low-to-intermediate risk individuals. We conducted a comprehensive search of Ovid (Embase and Medline), Cochrane Central Register of Controlled Trials (CENTRAL) and Medline complete (EBSCO health). A total of 30 papers were selected and data were extracted. Comparisons were made according to the cIMT measurement (mean, maximum), carotid plaque evaluation (presence or area), and CAC scoring. CVD event rates, hazard ratios (HR), net reclassification index (NRI), and c-statistic of the markers were compared. There were 27 studies that reported cIMT, 24 reported carotid plaque, and 6 reported CAC scoring. Inclusion of CAC scores yielded the highest HR ranging from 1.45 (95% CI, 1.11-1.88, p = 0.006) to 3.95 (95% CI, 2.97-5.27, p < 0.001), followed by maximum cIMT (HR 1.08; 95% CI, 1.06-1.11, p < 0.001 to 2.58; 95% CI, 1.83-3.62, p < 0.001) and carotid plaque presence (HR 1.21; 95% CI, 0.5-1.2, p = 0.39 to 2.43; 95% CI, 1.7-3.47, p < 0.001). The c-statistic enhanced predictive value by a minimum increase of 0.7. Finally, the NRI ranked higher with CAC (≥11.2%), followed by carotid plaque (≥2%) and cIMT (3%). CAC scoring was superior compared to carotid plaque and cIMT measurements in asymptomatic individuals classified as being at low-to-intermediate risk.

The Gut Microbiota and Their Metabolites in Human Arterial Stiffness.

AIM: Gut microbiota-derived metabolites, such as short-chain fatty acids (SCFAs) have vasodilator properties in animal and human ex vivo arteries. However, the role of the gut microbiota and SCFAs in arterial stiffness in humans is still unclear. Here we aimed to determine associations between the gut microbiome, SCFA and their G-protein coupled sensing receptors (GPCRs) in relation to human arterial stiffness. METHODS: Ambulatory arterial stiffness index (AASI) was determined from ambulatory blood pressure (BP) monitoring in 69 participants from regional and metropolitan regions in Australia (55.1% women; mean, 59.8± SD, 7.26 years of age). The gut microbiome was determined by 16S rRNA sequencing, SCFA levels by gas chromatography, and GPCR expression in circulating immune cells by real-time PCR. RESULTS: There was no association between metrics of bacterial α and ß diversity and AASI or AASI quartiles in men and women. We identified two main bacteria taxa that were associated with AASI quartiles: Lactobacillus spp. was only present in the lowest quartile, while Clostridium spp. was present in all quartiles but the lowest. AASI was positively associated with higher levels of plasma, but not faecal, butyrate. Finally, we identified that the expression of GPR43 (FFAR2) and GPR41 (FFAR3) in circulating immune cells were negatively associated with AASI. CONCLUSIONS: Our results suggest that arterial stiffness is associated with lower levels of the metabolite-sensing receptors GPR41/GPR43 in humans, blunting its response to BP-lowering metabolites such as butyrate. The role of Lactobacillus spp. and Clostridium spp., as well as butyrate-sensing receptors GPR41/GPR43, in human arterial stiffness needs to be determined.

Effects of Prone Sleeping on Cerebral Oxygenation in Preterm Infants.

OBJECTIVE: To determine the effect of prone sleeping on cerebral oxygenation in preterm infants in the neonatal intensive care unit. STUDY DESIGN: Preterm infants, divided into extremely preterm (gestational age 24-28 weeks; n = 23) and very preterm (gestational age 29-34 weeks; n = 33) groups, were studied weekly until discharge in prone and supine positions during active and quiet sleep. Cerebral tissue oxygenation index (TOI) and arterial oxygen saturation (SaO2) were recorded. Cerebral fractional tissue extraction (CFOE) was calculated as CFOE = (SaO2 - TOI)/SaO2. RESULTS: In extremely preterm infants, CFOE increased modestly in the prone position in both sleep states at age 1 week, in no change in TOI despite higher SaO2. In contrast, the very preterm infants did not have position-related differences in CFOE until the fifth week of life. In the very preterm infants, TOI decreased and CFOE increased with active sleep compared with quiet sleep and with increasing postnatal age. CONCLUSION: At 1 week of age, prone sleeping increased CFOE in extremely preterm infants, suggesting reduced cerebral blood flow. Our findings reveal important physiological insights in clinically stable preterm infants. Further studies are needed to verify our findings in unstable preterm infants regarding the potential risk of cerebral injury in the prone sleeping position in early postnatal life.

Comparison of the longitudinal effects of persistent periodic breathing and apnoea on cerebral oxygenation in term- and preterm-born infants.

KEY POINTS: Periodic breathing and apnoea were more common in preterm compared to age-matched term-born infants across the first 6 months after term-corrected age. Periodic breathing decreased with age in both term and preterm infants. Apnoea duration was not different between groups; however, the decline in apnoea index with postnatal age observed in the term infants was not seen in the preterm infants. Falls in tissue oxygenation index (brain TOI) associated with apnoeas were greater in the preterm infants at all three ages studied. The clinical significance of falls in brain TOI during periodic breathing and apnoea on neurodevelopmental outcome is unknown and warrants further investigations. ABSTRACT: Periodic breathing and short apnoeas are common in infants, particularly those born preterm, but are thought to be benign. The aim of our study was to assess the incidence and impact of periodic breathing and apnoea on heart rate, oxygen saturation and brain tissue oxygenation index (TOI) in infants born at term and preterm over the first 6 months after term equivalent age. Nineteen term-born infants (38-42 weeks gestational age) and 24 preterm infants (born at 27-36 weeks gestational age) were studied at 2-4 weeks, 2-3 months and 5-6 months post-term-corrected age during sleep. Periodic breathing episodes were defined as three or more sequential apnoeas each lasting ≥3 s and apnoeas as ≥3 s in duration. The mean duration of periodic breathing episodes was longer in term infants than in preterm infants at 2-4 weeks (P < 0.05) and at 5-6 months (P < 0.05); however, the nadir in TOI was significantly less in the term infants at 2-3 months (P < 0.001). Apnoea duration was not different between groups; however, the decline in apnoea index with postnatal age observed in the term infants was not seen in the preterm infants. Falls in TOI associated with apnoeas were greater in the preterm infants at all three ages studied. In conclusion, periodic breathing and short apnoeas were more common in infants born preterm and falls in cerebral oxygenation were greater than in the term group. The clinical significance of this on neurodevelopmental outcome is unknown and warrants further investigations.

The effect of sex and prematurity on the cardiovascular baroreflex response in sheep.

NEW FINDINGS: What is the central question of this study? Late preterm infants are often assumed to escape long-term morbidities known to impact earlier preterm offspring. Is this true for the cardiovascular system? What is the main finding and its importance? We show that late preterm birth is a risk factor for cardiovascular dysfunction in early adulthood and is influenced by sex. Early signs of cardiovascular dysfunction might predispose to heart disease in adulthood. Very preterm infants have an increased risk of cardiovascular disease; however, the effects of a late preterm birth on future cardiovascular function are not known. We hypothesized that after a late preterm birth, the well-described impairments in heart rate variability and baroreflex sensitivity would persist into adulthood. To test this hypothesis, sheep born preterm (0.9 gestation; nine male and seven female) or term (11 male and six female) underwent surgery at 14 months of age for insertion of femoral arterial and venous catheters and a femoral flow probe. After recovery, heart rate variability was assessed, followed by a baroreflex challenge (using the vasoactive agents phenylephrine and sodium nitroprusside) in conscious adult lambs. Our data demonstrate decreased low-frequency normalised units (LFnu) and low-frequency/high-frequency ratio in female but not male ex-preterm sheep at rest. When challenged, mature male ex-preterm sheep have an increased blood pressure response but dampened heart rate baroreflex response. We show that even a late preterm birth leads to cardiovascular dysfunction in adulthood. These early signs of cardiovascular dysfunction might underpin the later hypertension and increased risk of heart disease observed in adults born preterm. These findings are particularly important because late preterm infants are often assumed to escape the long-term morbidities known to impact on very preterm and extremely preterm offspring.

Effects of foetal growth restriction and preterm birth on cardiac morphology and function during infancy.

AIM: To investigate the effects of foetal growth restriction (FGR) and prematurity on cardiac morphology and function in infancy. We hypothesised that FGR and prematurity would both alter cardiac development. METHODS: Cardiac morphology and function were evaluated in 24 preterm FGR infants (p-FGR) and 23 preterm and 19 term appropriately grown for gestational age infants (p-AGA and t-AGA, respectively) by conventional echocardiography and Tissue Doppler Imaging. p-FGR and p-AGA infants were studied on postnatal day 1 and all groups were studied at one-and six-months post-term age. RESULTS: p-FGR infants demonstrated increased cardiac sphericity compared to AGA peers on postnatal day 1 (p = 0.004) and at one-month post-term age (p = 0.004). Posterior and relative wall thickness increased overtime in the p-FGR group only (p < 0.05). Systolic function was not different between groups. E/e' ratio was higher in both preterm groups compared to the term group at one-month post-term age (p = 0.01). No statistically significant group differences were found at six-months post-term age. CONCLUSION: Foetal growth restriction was associated with subtle cardiac morphological changes, whereas both prematurity and FGR were associated with subclinical alterations in diastolic function.

Fetal-growth-restricted preterm infants display compromised autonomic cardiovascular control on the first postnatal day but not during infancy.

BackgroundFetal growth restriction (FGR) is associated with increased perinatal mortality and long-term cardiovascular and neurodevelopmental sequelae. We hypothesized that FGR impacts on the development of autonomic heart rate and blood pressure control, contributing to unfavorable short- and long-term outcomes following FGR.MethodsWe studied 25 preterm FGR and 22 preterm and 19 term appropriate for gestational age (AGA) infants. Preterm neonates were studied on postnatal day 1, and all infants were studied at 1 and 6 months post-term age. To investigate autonomic cardiovascular control, we examined heart rate variability (HRV) and baroreflex sensitivity using spectral power and transfer-function analyses.ResultsPreterm FGR neonates exhibited higher heart rates and reduced HRV compared with preterm AGA controls on postnatal day 1. No significant differences were found between the three groups at 1 or 6 months post-term age.ConclusionPreterm FGR neonates display compromised HRV on postnatal day 1, which may suggest increased vulnerability to circulatory instability. This may predispose these neonates to systemic and cerebral hypoperfusion and increase the risk of long-term neurodevelopmental sequelae. Differences were no longer found at 1 and 6 months post-term age, suggesting that the maturation of autonomic cardiovascular control may be preserved following FGR.

Intrauterine growth restriction: impact on cardiovascular development and function throughout infancy.

Intrauterine growth restriction (IUGR) refers to the situation where a fetus does not grow according to its genetic growth potential. One of the main causes of IUGR is uteroplacental vascular insufficiency. Under these circumstances of chronic oxygen and nutrient deprivation, the growth-restricted fetus often displays typical circulatory changes, which in part represent adaptations to the suboptimal intrauterine environment. These fetal adaptations aim to preserve oxygen and nutrient supply to vital organs such as the brain, the heart, and the adrenals. These prenatal circulatory adaptations are thought to lead to an altered development of the cardiovascular system and "program" the fetus for life long cardiovascular morbidities. In this review, we discuss the alterations to cardiovascular structure, function, and control that have been observed in growth-restricted fetuses, neonates, and infants following uteroplacental vascular insufficiency. We also discuss the current knowledge on early life surveillance and interventions to prevent progression into chronic disease.

Dummy/pacifier use in preterm infants increases blood pressure and improves heart rate control.

BACKGROUND: Preterm infants are at increased risk of sudden infant death syndrome (SIDS). Use of a dummy/pacifier is thought to be protective against SIDS; accordingly, we assessed the effects of dummy/pacifier use on blood pressure, cerebral oxygenation, and heart rate control over the first 6 mo of life after term corrected age (CA) when SIDS risk is greatest. METHODS: Thirty-five preterm infants were studied longitudinally at 2-4 wk, 2-3 mo, and 5-6 mo CA. Cardiac control was assessed from spectral indices of heart rate variability (HRV) in the low frequency (LF) and the high frequency (HF) range, and the ratio of HF/LF indicating sympathovagal balance was calculated. RESULTS: Overall, at 2-3 mo, mean arterial pressure was significantly higher in the supine position in dummy/pacifier users in both quiet sleep (70 ± 2 vs. 60 ± 2 mm Hg; P < 0.05) and active sleep (74 ± 3 vs. 69 ± 2 mm Hg; P < 0.05). Dummy/pacifier users had higher LF HRV and LF/HF ratio and lower HF HRV. CONCLUSION: Dummy/pacifier use increased blood pressure during sleep, at the age of greatest SIDS risk. Overall, LF HRV was elevated and HF HRV reduced in dummy/pacifier users, suggesting that dummy use alters cardiac control in preterm infants.

Discrimination of sleep states using continuous cerebral bedside monitoring (amplitude-integrated electroencephalography) compared to polysomnography in infants.

AIM: Limited two-channel electroencephalography (EEG) and amplitude-integrated EEG (aEEG) monitorings are being increasingly used; however, these measurements have not been compared with polysomnographic monitoring, the gold standard for determining infant sleep states. We aimed to determine the accuracy of two-channel EEG and aEEG recordings in defining sleep states and wakefulness in term infants compared to polysomnographic monitoring. METHODS: Sleep was assessed in eight healthy term born infants (mean: 34 ± 3 days), using simultaneous polysomnography (Compumedics S-Series) and a two-channel EEG monitor (Brainz BRM2). EEG intensity, 90% spectral edge frequency (SEF), aEEG amplitude frequency bands were analysed in 30-second epochs during quiet sleep, active sleep and awake as determined by polysomnography. RESULTS: BRM2-recorded EEG accurately identified quiet sleep from active sleep for EEG intensity (p = 0.003), SEF (p = 0.001) and aEEG amplitude (p = 0.003) and quiet sleep from awake, but not active sleep from awake. Frequency band analysis showed that wake could be identified by changes in absolute power (p = 0.015) and frequency as a percentage of total power (p = 0.03). CONCLUSION: We demonstrate that limited two-channel EEG monitoring can distinguish quiet sleep from active sleep and may be suitable for investigating the development of sleep in infants in the neonatal intensive care setting.

Gestational age at birth affects maturation of baroreflex control.

OBJECTIVES: To assess the effect of prone sleeping, the major risk factor for sudden infant death syndrome, in the control of blood pressure (BP) in preterm infants born across a range of gestational ages. STUDY DESIGN: Daytime polysomnography was performed at 2-4 weeks, 2-3 months, and 5-6 months postterm age. The participants were 21 very preterm (mean gestation 29.4 ± 0.3 weeks), 14 preterm (mean gestation 33.1 ± 0.3 weeks), and 17 term (mean gestation 40.1 ± 0.3 weeks). BP was measured via a Finometer cuff (Finapres Medical Systems, Amsterdam, The Netherlands) placed around the wrist. Data were recorded both supine and prone. Baroreflex sensitivity (BRS) was calculated via cross-spectral analysis of spontaneous fluctuations in BP. RESULTS: BRS was lower in the prone position in very preterm infants at 2-4 weeks in active sleep (P < .05). Maturation of BRS was delayed in very preterm compared with both preterm and term infants. CONCLUSIONS: Maturation of BRS after term-equivalent age is altered in very preterm infants. Reduced BRS may result in an impaired ability of very preterm infants to respond to cardiovascular stress during infancy and may predispose them to cardiovascular disease later in life.

Pacifier use does not alter sleep and spontaneous arousal patterns in healthy term-born infants.

AIM: Impaired arousal from sleep has been implicated in sudden infant death syndrome (SIDS). Sleeping in the prone position is a major risk factor for SIDS. Epidemiological studies have shown that pacifier use decreases the risk of SIDS, even when infants sleep prone. We examined spontaneous arousability in infants slept prone and supine over the first 6 months of life and hypothesised that spontaneous arousals would be increased in pacifier users, particularly in the prone position. METHODS: Healthy term infants (n = 30) were studied on three occasions over the first 6 months after birth. Spontaneous cortical arousals and subcortical activations were scored and converted into frequency per hour of sleep. RESULTS: There was no effect of pacifier use on total time spent sleeping or awake or the number of spontaneous awakenings at any age. There was also no effect of pacifier use on the frequency or duration of the total number of spontaneous arousals or on cortical arousals and subcortical activations. CONCLUSION: Pacifier use did not alter infant spontaneous arousability at any of the three ages studied, in either the prone or supine sleeping position. Any preventative effect of pacifiers for SIDS may be through physiological mechanisms other than increased arousability.

Association of the Sleep Regularity Index With Incident Dementia and Brain Volume.

BACKGROUND AND OBJECTIVES: Irregular sleep may increase the risk of cardiometabolic conditions, but its association with incident dementia is unclear. The aim of this study was to assess the association between sleep regularity, that is, the day-to-day consistency in sleep-wake patterns and the risk of incident dementia and related brain MRI endophenotypes. METHODS: We used Cox proportional hazard models to investigate the relationships between sleep regularity and incident dementia in 88,094 UK Biobank participants. The sleep regularity index (SRI) was calculated as the probability of being in the same state (asleep/awake) at any 2 time points 24 hours apart, averaged over 7 days of accelerometry. RESULTS: The mean age of the sample was 62 years (SD = 8), 56% were women, and the median SRI was 60 (SD = 10). There were 480 cases of incident dementia over a median 7.2 years of follow-up. Following adjustments for demographic, clinical, and genetic confounders (APOE ε4), there was a nonlinear association between the SRI and dementia hazard (p [global test of spline term] < 0.001) with hazard ratios (HRs) following a U-shape pattern. HRs, relative to the median SRI, were 1.53 (95% CI 1.24-1.89) for participants with SRI at the 5th percentile (SRI = 41) and 1.16 (95% CI 0.89-1.50) for those with SRI at the 95th percentile (SRI = 71). In a subset with brain MRI (n = 15,263), gray matter and hippocampal volume tended to be lowest at the extremes of the SRI. DISCUSSION: Sleep regularity displayed a U-shaped association with risk of incident dementia. Irregular sleep may represent a novel dementia risk factor.