Being born preterm, small, and to a mother who smokes are common perinatal complications with major public health implications. Evidence suggests that each affects the body's structure and function ...in ways that could increase susceptibility to cardiovascular dysfunction later in life. Here, we used 2 routine stress reactivity tests to identify incipient "silent" programming of cardiovascular dysfunction associated with adverse perinatal events.
We studied 29 control babies born at term to nonsmokers, 18 term-born babies of mothers who smoked throughout pregnancy (mean, 15 cigarettes a day), and 31 babies born preterm to nonsmokers. All infants were compared at the same age after conception (ie, at 40 to 42 weeks), during sleep. We analyzed blood pressure (BP) and heart rate responses to breathing 4% CO(2) for 4 minutes or to passive head-up tilt to 60 degrees . BP was measured continuously from a wrist cuff. CO(2) exposure raised heart rate and BP in controls by 10%, and tilt increased their BP by 5%. CO(2) elicited the expected BP but no heart rate response from preterm infants but a much-greater-than-expected BP and heart rate response from babies of smokers. Tilt elicited a 3- to 4-fold greater rise in BP from preterm and tobacco-exposed babies.
Vascular, cardiac, and blood pressure reactivity is heightened in babies born preterm or to smokers. The findings are consistent with in utero and early postnatal "programming" of human cardiovascular dysfunction by adverse circumstances. This incipient dysfunction may be an early manifestation of processes that lead to other problems or complications later on (eg, higher BP or sudden infant death syndrome).
Summary
Obstructive sleep apnea (OSA), often concomitant with obesity, increases the risk for the metabolic syndrome. One mechanism that may participate in this association is upregulation of ...inflammatory pathways. We used structural equation modeling to assess the interrelations between childhood obesity, OSA, inflammation, and metabolic dysfunction. One hundred and eighty‐four children (127 boys, mean age: 8.5 ± 4.1years) had height and weight measured, underwent overnight polysomnography and had fasting blood taken. The blood was analyzed for insulin, glucose, lipids, leptin, and cytokines interferon (IFN)‐γ, granulocyte macrophage–colony stimulating factor, interleukin (IL)‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, tumor necrosis factor‐α. Structural equation modeling (SEM) was used to evaluate associations between the outcomes of interest including hypoxia, arousal (related to respiratory and spontaneous), obesity, metabolic dysfunction, and inflammatory markers. Two cytokine factors and one metabolic factor were derived for the SEM. These factors provided good fit in the structural equation model (χ2/df = 2.855; comparative fit index = 0.90, root mean squared error of approximation = 0.10) and all factor loadings were significantly different from zero (P ≤ 0.01). Overall, our results indicate that while obesity (as measured by body mass index z‐score) has a major influence on the metabolic dysfunction associated with OSA, arousal indices, and cytokine markers may also influence this association. Our results support the hypothesis that OSA is a contributor to the mechanisms that link sleep, systemic inflammation and insulin resistance, and show that the interrelations may begin in childhood.
Sleepwalking is a dissociation between body sleep and mind sleep. We report single photon emission computed tomography (SPECT) in a man with a history of sleepwalking. Our findings suggest that this ...dissociation arises from activation of thalamocingulate pathways and persisting deactivation of other thalamocortical arousal systems.
In adults, obstructive sleep apnea (OSA) is associated with metabolic dysfunction that improves with treatment of OSA. No equivalent studies exist in children.
To examine the relationship between ...metabolic markers and OSA with time and treatment in children.
Metabolic markers measured on a fasting morning blood sample at diagnostic polysomnography and follow-up 1.3 +/- 0.6 yr later.
Forty-five children (34 males), aged 6.9 +/- 3.5 yr, and including 12 obese subjects, were in the final analysis. There were no differences in metabolic markers between children with and without OSA at initial study; however, obese children had significantly higher insulin (106.1 +/- 72.1 vs. 66.7 +/- 37.6 pmol/L; p = 0.028), insulin/glucose ratio (23.7 +/- 14.3 vs. 14.7 +/- 8.0; p = 0.02), and significantly lower high-density lipoprotein cholesterol (1.3 +/- 0.2 vs. 1.6 +/- 0.4 nmol/L; p = 0.005) than nonobese children. Twenty children underwent surgical removal of adenotonsillar tissue, whereas 12 children with OSA elected not to have treatment. OSA persisted after treatment in five children, and resolved in 27. Thirteen children did not have OSA on initial or follow-up studies. At follow-up, there was a small but significant improvement in total cholesterol in those children whose OSA was resolved (4.8 +/- 0.8 to 4.7 +/- 0.6 nmol/L; p = 0.005) and a trend for obese children with persisting OSA to have elevated insulin levels compared with obese children without OSA (p = 0.07).
Obesity appears to be the major influence on metabolic dysfunction in children with OSA, but these preliminary data also suggest that resolution or persistence of OSA may affect changes in metabolic function over time.
Key points
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Fast‐acting reflexes fine‐tune heart rate and blood pressure as the push and pull of gravity changes from moment to moment.
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Circulatory failure may occur if these mechanisms fail to ...develop normally.
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Reactions to routine movements such as head‐up and sideways tilt show how two key reflexes involved develop during sleep, in early infancy.
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Sensors that detect motion and arterial pulsations, located in the inner ear and arteries, respectively, produce carefully coordinated changes in heart rate and blood pressure as body position and the force/direction of gravity alters.
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Both mechanisms are intact in infants exposed to tobacco, but a mild pulse pressure anomaly reflexively slows their heart and lowers their blood pressure on tilt to upright.
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Circulatory dysfunction need not necessarily reflect abnormal development of key reflexes per se, but other factors that inappropriately trigger or inhibit them.
Heart rate (HR) and arterial blood pressure (BP) are rapidly and reflexively adjusted as body position and the force/direction of gravity alters. Anomalies in these mechanisms may predispose to circulatory failure during sleep. We analysed the development of two key reflexes involved by undertaking a longitudinal (birth–1 year) comparison of instantaneous HR and BP changes evoked by abrupt upright, sideways or horizontal repositioning. Each manoeuvre triggered an identical rise in HR (tachycardia) followed by a slower rise in diastolic blood pressure (DBP)/systolic blood pressure (SBP) and variable pulse pressure (PP) change. We show that tachycardia is triggered by acceleration (vestibular) sensors located in the inner ear and slight changes in the pulsatile component of BP then signal to the arterial baroreceptors to reinforce or oppose these actions as needed. We also identified a PP anomaly in sleeping 1‐year‐olds of smokers that prematurely slows HR and is associated with mild positional hypotension. We conclude that positional circulatory compensation is initiated pre‐emptively in a feed‐forward manner and that feedback changes in vago‐sympathetic drive to the heart (and perhaps blood vessels) by PP exert a slower but powerful modulating effect. An anomaly in either or both mechanisms may weaken positional compensation in some sleeping infants.
During a 3-y period 13 newborns were referred for investigation of jerks. The events were epileptic in six children. The diagnosis of benign neonatal sleep myoclonus was made in the remaining seven ...children.
Benign neonatal sleep myoclonus is an important neonatal entity that can be mistaken for epilepsy.
We describe extended and repeat magnetic resonance (MR) examinations in the case of a 16-year-old male who developed acute left-sided sensorimotor hemiplegia after a single dose of inhaled heroin. ...MRI revealed symmetrical hyperintense signals in T 2 -weighted images and massive diffusion disorders in the diffusion weighted images predominantly in parieto-occipital subcortical white matter and both ventral globi pallidi with preservation of U fibers and no brain oedema. MR spectroscopy data were compatible with combined hypoxic and mitochondrial damage resulting in axonal injury without demyelination. Normal values and variations had been obtained from spectra of five age-matched subjects. This is the first reported MR follow-up study of leukoencephalopathy occurring acutely after a first inhaled dose of heroin. We postulate that toxic spongiform leukoencephalopathy in heroin addicts may be the outcome of a complex mechanism directly triggered by heroin and causing mitochondrial as well as hypoxic injury in specific and limited areas of white matter.
During a 3‐y period 13 newborns were referred for investigation of jerks. The events were epileptic in six children. The diagnosis of benign neonatal sleep myoclonus was made in the remaining seven ...children.
Conclusion: Benign neonatal sleep myoclonus is an important neonatal entity that can be mistaken for epilepsy.
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