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.

Cross-sectional associations between neighborhood characteristics, cognition and dementia risk factor burden in middle-aged and older Australians.

Dementia disproportionately affects individuals from disadvantaged backgrounds, including those living in areas of lower neighborhood-level socioeconomic status. It is important to understand whether there are specific neighborhood characteristics associated with dementia risk factors and cognition which may inform dementia risk reduction interventions. We sought to examine whether greenspace, walkability, and crime associated with the cumulative burden of modifiable dementia risk factors and cognition. This was a cross-sectional analysis of 2016-2020 data from the Healthy Brain Project, a population-based cohort of community-dwelling individuals across Australia. Participants were aged 40-70 and free of dementia. Measures included greenspace (greenspace % in the local area, and distance to greenspace, n = 2,181); and intersection density (n = 1,159), and crime (rate of recorded offences; n = 1,159). Outcomes included a modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score to index the burden of modifiable vascular dementia risk factors; and composite scores of both memory and attention, derived from the Cogstate Brief Battery. Linear regressions adjusted for age, sex, education, and personal socio-economic status, demonstrated distance to greenspace (b ± SE per 2-fold increase = 0.09 ± 0.03, p =.005) and crime rate (b ± SE per 2-fold increase = 0.07 ± 0.03, p =.018) were associated with higher modified CAIDE. Higher crime was associated with lower memory performance (b ± SE = -0.03 ± 0.01, p =.018). The association between distance to greenspace and modified CAIDE was only present in low-moderate socioeconomic status neighborhoods (p interaction = 0.004). Dementia prevention programs that address modifiable risk factors in midlife should consider the possible role of neighborhood characteristics.

Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology.

BACKGROUND AND OBJECTIVES: Both short and long sleep duration were previously associated with incident dementia, but underlying mechanisms remain unclear. We evaluated how self-reported sleep duration and its change over time associate with (A)myloid, (T)au, (N)eurodegeneration, and (V)ascular neuroimaging markers of Alzheimer disease. METHODS: Two Framingham Heart Study overlapping samples were studied: participants who underwent 11C-Pittsburg Compound B amyloid and 18F-flortaucipir tau PET imaging and participants who underwent an MRI. MRI metrics estimated neurodegeneration (total brain volume) and cerebrovascular injuries (white matter hyperintensities [WMHs] volume, covert brain infarcts, free-water [FW] fraction). Self-reported sleep duration was assessed and split into categories both at the time of neuroimaging testing and approximately 13 years before: short ≤6 hours. average 7-8 hours, and long ≥9 hours. Logistic and linear regression models were used to examine sleep duration and neuroimaging metrics. RESULTS: The tested cohort was composed of 271 participants (age 53.6 ± 8.0 years; 51% male) in the PET imaging sample and 2,165 participants (age 61.3 ± 11.1 years; 45% male) in the MRI sample. No fully adjusted association was observed between cross-sectional sleep duration and neuroimaging metrics. In fully adjusted models compared with consistently sleeping 7-8 hours, groups transitioning to a longer sleep duration category over time had higher FW fraction (short to average ß [SE] 0.0062 [0.0024], p = 0.009; short to long ß [SE] 0.0164 [0.0076], p = 0.031; average to long ß [SE] 0.0083 [0.0022], p = 0.002), and those specifically going from average to long sleep duration also had higher WMH burden (ß [SE] 0.29 [0.11], p = 0.007). The opposite associations (lower WMH and FW) were observed in participants consistently sleeping ≥9 hours as compared with people consistently sleeping 7-8 hours in fully adjusted models (ß [SE] -0.43 [0.20], p = 0.028; ß [SE] -0.019 [0.004], p = 0.020). Each hour of increasing sleep (continuous, ß [SE] 0.12 [0.04], p = 0.003; ß [SE] 0.002 [0.001], p = 0.021) and extensive increase in sleep duration (≥2 hours vs 0 ± 1 hour change; ß [SE] 0.24 [0.10], p = 0.019; ß [SE] 0.0081 [0.0025], p = 0.001) over time was associated with higher WMH burden and FW fraction in fully adjusted models. Sleep duration change was not associated with PET amyloid or tau outcomes. DISCUSSION: Longer self-reported sleep duration over time was associated with neuroimaging biomarkers of cerebrovascular pathology as evidenced by higher WMH burden and FW fraction. A longer sleep duration extending over time may be an early change in the neurodegenerative trajectory.

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.

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.

The treatment of sleep dysfunction to improve cognitive function: A meta-analysis of randomized controlled trials.

OBJECTIVE: This meta-analysis of randomized controlled trials (RCTs) evaluates if treating sleep disturbances improves cognitive function over at least 12 weeks. METHODS: Multiple data sources were searched until November 1, 2021. RCTs were included if they examined the effect of an intervention (behavioral or medical) on sleep and cognition in an adult sample with sleep disturbances and had an intervention duration and follow-up of at least 12 weeks. Two independent reviewers located 3784 studies; 16 satisfied the inclusion criteria. Primary outcomes included the broad cognitive domains of visual processing, short-term memory, long-term storage and retrieval, processing speed, and reaction time. RESULTS: Most trials were conducted in participants with obstructive sleep apnea (OSA; N = 13); the most studied intervention was continuous positive airway pressure (CPAP; N = 10). All RCTs were 12 months in duration or less. The estimates of mean pooled effects were not indicative of significant treatment effect for any primary outcome. Although the interventions reduced daytime sleepiness (Hedge's g, 0.51; 95% confidence interval, 0.29-0.74; p < 0.01), this did not lead to cognitive enhancement. CONCLUSIONS: Overall, there was insufficient evidence to suggest that treating sleep dysfunction can improve cognition. Further studies with longer follow-up duration and supporting biomarkers are needed.

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.

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.

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.

When does prone sleeping improve cardiorespiratory status in preterm infants in the NICU?

STUDY OBJECTIVES: Preterm infants undergoing intensive care are often placed prone to improve respiratory function. Current clinical guidelines recommend preterm infants are slept supine from 32 weeks' postmenstrual age, regardless of gestational age at birth. However, respiratory function is also related to gestational and chronological ages and is affected by sleep state. We aimed to identify the optimal timing for adopting the supine sleeping position in preterm infants, using a longitudinal design assessing the effects of sleep position and state on cardiorespiratory stability. METHODS: Twenty-three extremely (24-28 weeks' gestation) and 33 very preterm (29-34 weeks' gestation) infants were studied weekly from birth until discharge, in both prone and supine positions, in quiet and active sleep determined by behavioral scoring. Bradycardia (heart rate ≤100 bpm), desaturation (oxygen saturation ≤80%), and apnea (pause in respiratory rate ≥10 s) episodes were analyzed. RESULTS: Prone positioning in extremely preterm infants reduced the frequency of bradycardias and desaturations and duration of desaturations. In very preterm infants, prone positioning only reduced the frequency of desaturations. The position-related effects were not related to postmenstrual age. Quiet sleep in both preterm groups was associated with fewer bradycardias and desaturations, and also reduced durations of bradycardia and desaturations in the very preterm group. CONCLUSIONS: Cardiorespiratory stability is improved by the prone sleep position, predominantly in extremely preterm infants, and the improvements are not dependent on postmenstrual age. In very preterm infants, quiet sleep has a more marked effect than the prone position. This evidence should be considered in individualizing management of preterm infant positioning.

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.

Being Born Too Small and Too Early May Alter Sleep in Childhood.

STUDY OBJECTIVES: Fetal growth restriction (FGR) occurs in up to 10% of pregnancies and is associated with increased risk of prematurity and neurodevelopmental impairment. FGR also alters sleep-state distribution in utero and maturation in infancy. Currently, limited data on the long-term associations of FGR and childhood sleep exist. Accordingly, we assessed the associations between preterm birth and FGR and sleep in children aged 5-12 years. METHODS: Seventeen children born preterm and FGR, 15 children born preterm but appropriately grown (appropriate birth weight for gestational age [AGA]), and 20 term AGA children (controls) were studied using overnight polysomnography. Sleep macroarchitecture was assessed using standard criteria, and sleep microarchitecture was assessed using spectral analysis of the electroencephalogram (C4-M1) with total, δ (0.5-3.9 Hz), θ (4.0-7.9Hz), α (8.0-11.9 Hz), σ (12.0-13.9 Hz), and ß power (14.0-30 Hz) calculated. RESULTS: For sleep macroarchitecture, preterm FGR children had higher N2% compared with term AGA children (p < .05). Preterm AGA children had reduced total sleep time, NREM%, and sleep efficiency compared with term AGA children (p < .05 for all). For sleep microarchitecture, preterm FGR children had a higher amount of total, δ and α power compared with both groups (p < .05). Sigma and ß power was lowest in the preterm AGA group compared with both groups (p < .05 for both). CONCLUSIONS: Prematurity and FGR were associated with altered sleep macro- and microarchitecture measures indicative of reduced sleep quantity and quality in childhood. As sleep disturbance can affect both behavior and neurodevelopment in children, sleep in FGR and preterm children warrants further investigation.

Prone sleeping position in infancy: Implications for cardiovascular and cerebrovascular function.

Advances in neonatal care have improved the survival rates of preterm infants, however, the likelihood of brain injury and neurodevelopmental disability remains a significant problem. Whilst the etiology of preterm brain injury is complex, impairments in the cardio- and cerebro-vascular function have been implicated. During infancy, sleep is vital for brain development. However, instabilities in cardio- and cerebro-vascular function are most marked during sleep. Sleeping position is an important part of a safe sleeping environment. Prone sleeping increases the risk of sudden infant death syndrome and is associated with reduced blood pressure, cerebral oxygenation and impaired autonomic cardiovascular control in infants born at term. Importantly, these effects are amplified by preterm birth. Hospitalized preterm infants are often slept in the prone position to improve respiratory function. However, there is little consensus regarding the sustained benefits of prone sleeping in this population. In light of the impaired cardio- and cerebro-vascular function during prone sleeping in term and preterm infants after hospital discharge, the likely adverse effects of prone sleeping in hospitalized preterm infants are concerning. This review examines the cardiovascular and cerebrovascular effects of prone sleeping in infants born at term, those born preterm after term equivalent age and whilst hospitalized.

EEG power spectrum maturation in preterm fetal growth restricted infants.

Power spectral analysis of the electroencephalogram (EEG) is a non-invasive method to examine infant brain maturation. Preterm fetal growth restricted (p-FGR) neonates display an altered EEG power spectrum compared to appropriate-for-gestational-age (AGA) peers, suggesting delayed brain maturation. Longitudinal studies investigating EEG power spectrum maturation in p-FGR infants are lacking, however. We thus aimed to investigate brain maturation using sleep EEG power spectral analysis in p-FGR infants compared to preterm and term AGA controls (p-AGA and t-AGA, respectively). EEG was recorded during spontaneous sleep in 13 p-FGR, 17 p-AGA and 19 t-AGA infants at 1 and 6 months post-term age. Infant sleep states (active and quiet sleep) were scored using standard criteria. Power spectral analysis of a single-channel EEG (C3-M2/C4-M1) was performed using Fast Fourier Transform. The EEG power spectrum was divided into delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), sigma (12-14 Hz) and beta (14-30 Hz) frequency bands. Relative (%) powers and the spectral edge frequency were calculated. The spectral edge frequency was significantly higher in p-FGR infants compared to p-AGA controls in quiet sleep at 1 month post-term age (p < .01). This was due to significantly reduced %-delta and significantly increased %-theta, %-alpha and %-beta power (p < .01 for all) compared to p-AGA infants. p-FGR infants also showed significantly increased %-beta power compared to t-AGA infants (p < .05). No group differences were observed in active sleep or at 6 months post-term age. In conclusion, p-FGR infants show altered sleep EEG power spectrum maturation compared to AGA peers. However, changes resolved by 6 months post-term age.

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.