Riva Tauman

Obesity Rather Than Severity of Sleep-Disordered Breathing as the Major Determinant of Insulin Resistance and Altered Lipidemia in Snoring Children

Objective. Sleep-disordered breathing (SDB) is associated with insulin resistance and dyslipidemia in adults and in obese children. However, the prevalence of such metabolic abnormalities among snoring children is unknown. This study was done to prospectively assess the relative contribution of SDB and obesity to metabolic disturbances in a large cohort of snoring children. Methods. Measurements of fasting serum glucose, insulin, and lipids were obtained after polysomnographic evaluation in 116 snoring children and in 19 control subjects. Insulin resistance was assessed using the insulin/glucose ratio (I/G ratio) and homeostasis model assessment (HOMA). Results. A total of 135 children (79 boys; mean age: 8.9 ± 3.5 years) were studied. Sixty-four children had moderate to severe SDB (AHI = 5 per hour of total sleep time [TST]), 52 had mild SDB (AHI = 1 but <5 per hour of TST), and 19 were control subjects (AHI <1 per hour of TST). Seventy of these children were obese. No significant correlations were found between AHI, lowest arterial oxygen saturation, or arousal index and serum insulin, serum glucose, I/G ratio, HOMA, or serum lipids for either the whole group or the obese children only. However, significant positive correlations were found between I/G ratio and relative BMI (relBMI; r = 0.58), HOMA and relBMI (r = 0.52), triglycerides and relBMI (r = 0.30), and high-density lipoprotein and relBMI (r = 0.50). No significant differences were found in relBMI, I/G ratio, and lipid levels between boys and girls. Conclusions. Among children with suspected SDB, insulin resistance and dyslipidemia seem to be determined primarily by the degree of body adiposity rather than by the severity of SDB.

Modafinil in the treatment of excessive daytime sleepiness in children

BACKGROUND Modafinil is an alerting agent approved for the treatment of narcolepsy in adults. There are no studies examining the long-term effects and safety profile of modafinil in children with excessive daytime somnolence (EDS). OBJECTIVES To determine the effects of modafinil on clinical manifestations of narcolepsy and idiopathic hypersomnia. METHODS A systematic chart review was conducted for 13 children (mean age 11.0+/-5.3 years, six males, 10 with narcolepsy and three with idiopathic hypersomnia) receiving modafinil. RESULTS The mean modafinil dose was 346+/-119 mg/day, with a mean treatment duration of 15.6+/-7.8 months. For approximately 90% of the children treated, parents reported a favorable response with the reduction in sudden sleep attacks, as documented by sleep-wake diaries. One child failed to improve on 400 mg/day modafinil and was switched to methylphenidate. Two other children showed only partial improvement and required additional stimulant medication to control EDS symptoms. Seven children underwent repeated nocturnal polysomnography and multiple sleep latency tests (MSLT). Compared to baseline MSLT measures (mean sleep latency: 6.6+/-3.7 min), modafinil prolonged mean sleep latency (10.2+/-4.8 min, p=0.02) without significant alteration in nocturnal polysomnographic measures. However, a trend towards REM sleep reduction was noted (16.8+/-5.1%TST vs. 11.8+/-6.2%TST). Exacerbation of seizures and psychotic symptoms was reported with modafinil therapy in two children with preexisting conditions. Hematological and hepatic functions assessed every 3 months remained unaltered. CONCLUSION Modafinil has a modest, yet significant effect on EDS in children and appears to be safe and well tolerated.

Obstructive sleep apnea syndrome in children

The clinical syndrome of obstructive sleep apnea (OSAS) in children is a distinct, yet somewhat overlapping disorder with the condition that occurs in adults, such that the clinical manifestations, polysomnographic findings, diagnostic criteria and treatment approaches need to be considered in an age-specific manner. Childhood OSAS has now become widely recognized as a frequent disorder and as a major public health problem. Pediatric OSAS, particularly when obesity is concurrently present, is associated with substantial end-organ morbidities and increased healthcare utilization. Although adenotonsillectomy (T&A) remains the first line of treatment, evidence in recent years suggests that the outcomes of this surgical procedure may not be as favorable as expected, such that post-T&A polysomnographic evaluation may be needed, especially in high-risk patient groups. In addition, incorporation of nonsurgical approaches for milder forms of the disorder and for residual OSAS after T&A is now being investigated.

Serum Proteomic Patterns Associated With Sleep-Disordered Breathing in Children

Obstructive sleep apnea (OSA) is a major public health problem affecting approximately 2% to 3% of children. However, snoring, the cardinal symptom of OSA, affects at least 5-fold more children, such that evaluation by overnight polysomnography (ONP) is required for the diagnosis. ONP is laborious, expensive, and relatively unavailable to children. Proteomic mass spectrometry coupled with bioinformatic tools provide valuable means for discovery of new biomarkers in serum for a variety of human disorders. The possibility exists that snoring children with and without OSA may exhibit different protein expression profiles in serum that could be useful in the development of novel diagnostic tools for this condition. The proteomic patterns of 20 children with OSA and of 20 children with habitual primary snoring but no evidence of OSA (HS) were evaluated using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Linear discriminative analysis identified three differentially regulated proteins with molecular masses of 5896, 3306, 6068 Da that were capable of diagnosing OSA with 93% sensitivity and 90% specificity. Thus, the proteomic signatures of sera from children with OSA differ from those of HS who do not fulfill the current criteria for treatment. Identification and sequencing of those differentially expressed proteins discovered through proteomic strategies may lead to future development of serum-based diagnostic tests for OSA in snoring children.

Maternal snoring during pregnancy is associated with enhanced fetal erythropoiesis – a preliminary study

OBJECTIVE AND BACKGROUND Snoring is common among pregnant women and early reports suggest that it may bear a risk to the fetus. Increased fetal erythropoiesis manifested by elevated circulating nucleated red blood cells (nRBCs) has been found in complicated pregnancies involving fetal hypoxia. Both erythropoietin (EPO) and interleukin-6 (IL-6) mediate elevation of circulating nRBCs. The intermittent hypoxia and systemic inflammation elicited by sleep-disordered breathing (SDB) could affect fetal erythropoiesis during pregnancy. We hypothesized that maternal snoring will result in increased levels of fetal circulating nRBCs via increased concentrations of EPO, IL-6, or both. METHODS Women of singleton uncomplicated full-term pregnancies were recruited during labor and completed a designated questionnaire. Umbilical cord blood was collected immediately after birth and analyzed for nRBCs, plasma EPO and plasma IL-6 concentrations. Newborn data were retrieved from medical records. RESULTS One hundred and twenty-two women were recruited. Thirty-nine percent of women reported habitual snoring during pregnancy. Cord blood levels of circulating nRBCs, EPO and IL-6 were significantly elevated in habitual snorers compared with non-snorers (p = 0.03, 0.005 and 0.01; respectively). No differences in maternal characteristics or newborn crude outcomes were found. CONCLUSIONS Maternal snoring during pregnancy is associated with enhanced fetal erythropoiesis manifested by increased cord blood levels of nRBCs, EPO and IL-6. This provides preliminary evidence that maternal snoring is associated with subtle alterations in markers of fetal well being.

Melatonin production in infants

This study investigated the relationships of the excretion of the melatonin metabolite, 6-sulfatoxymelatonin, to prenatal, natal, and postnatal variables and its possible relation to psychomotor development. nocturnal urinary excretion of 6-sulfatoxymelatonin was studied over a 13-hour period in 355 term infants at 8 weeks of age (n = 320) and 16 weeks of age (n = 96). data on a variety of perinatal factors including pregnancy course, delivery, early postnatal course, birth weight, medical problems, growth (length, weight, and head circumference), and psychomotor development were collected at 1, 3, 6, 9, 12, and 18 months. the relationship between nocturnal 6-sulfatoxymelatonin excretion at 8 and 16 weeks of age and these factors was investigated and analyzed. 6-sulfatoxymelatonin levels at 16 weeks of age were significantly lower in infants with abnormal vs normal development at 3 months of age (7.27 + 1.44 vs 7.97 + 1.06, p = 0.05) as well as at 6 months of age (7.15 + 1.29 vs 7.95 + 1.10, p = 0.04). no other significant relation was evident among growth, perinatal complications, medical problems, and 6-sulfatoxymelatonin excretion at 8 weeks of age and at 16 weeks of age. low melatonin excretion in the first weeks of life correlates with delayed psychomotor achievements at 3 and 6 months of age. this association suggests a causal or predictive link between melatonin and neurodevelopment in infants.

Insulin Sensitivity, Serum Lipids, and Systemic Inflammatory Markers in School-Aged Obese and Nonobese Children

The impact of obesity as a systemic low-grade inflammatory process has only partially been explored. To this effect, 704 community-based school-aged children (354 obese children and 350 age-, gender-, and ethnicity-matched controls) were recruited and underwent assessment of plasma levels of fasting insulin and glucose, lipids, and a variety of proinflammatory mediators that are associated with cardiometabolic dysfunction. Obese children were at higher risk for abnormal HOMA and cholesterol levels. Furthermore, BMI z score, HOMA, and LDL/HDL ratio strongly correlated with levels of certain inflammatory mediators. Taken together, obesity in children is not only associated with insulin resistance and hyperlipidemia, but is accompanied by increased, yet variable, expression of markers of systemic inflammation. Future community-based intervention and phenotype correlational studies on childhood obesity will require inclusion of expanded panels of inflammatory biomarkers to provide a comprehensive assessment of risk on specific obesity-related morbidities.

Maternal snoring during pregnancy is not associated with fetal growth restriction

A small number of studies have, thus far, evaluated the association between maternal snoring and fetal growth revealing conflicting results. No study has compared fetal growth between women with habitual snoring who snored before pregnancy and women with habitual snoring that started to snore during pregnancy. Objectives: To examine the effect of maternal snoring on fetal outcome and to investigate the differences between “chronic snorers” and “new-onset snorers”. Methods: Women of singleton, uncomplicated, full-term pregnancies completed a questionnaire. Obstetric and labor records were reviewed. Newborn records were reviewed for gestational age, birth weight, Apgar score and gender. Results: 246 low risk women were studied. Mean BMI at the beginning of pregnancy was 22.3 ± 3.5 kg/m2. 32% reported habitual snoring. Of those, 26% were chronic snorers and 74% were new-onset snorers. Neither significant difference in fetal growth was found between snorers and non-snorers nor between chronic snorers and new-onset snorers. Increased rate of nulliparous women was found in new-onset snorers compared with both chronic snorers and non-snorers (54 vs. 25 and 29% respectively; p = 0.001). Conclusions: In pregnant women with no apparent risk factors, maternal snoring does not affect fetal growth. No differences in maternal characteristics or fetal outcome were found between chronic snorers and new-onset snorers.

Coexistence of Sleep and Feeding Disturbances in Young Children

OBJECTIVE: Behavioral insomnia and feeding difficulties are 2 prevalent conditions in healthy young children. Despite similarities in nature, etiology, prevalence, and age distribution, the association between these 2 common disorders in young children has not been examined thus far. PATIENTS AND METHODS: Children aged 6 to 36 months with either behavioral insomnia or feeding disorders were recruited. Children aged 6 to 36 months who attended the well-care clinics were recruited and served as controls. Sleep and feeding were evaluated by using a parental questionnaire. RESULTS: Six hundred eighty-one children were recruited. Fifty-eight had behavioral insomnia, 76 had feeding disorders, and 547 were controls. The mean age was 17.0 ± 7.6 months. Parents of children with feeding disorders considered their childs sleep problematic significantly more frequently compared with controls (37% vs 16%, P = .0001 [effect size (ES): 0.66]). They reported shorter nocturnal sleep duration and delayed sleep time compared with controls (536 ± 87 vs 578 ± 88 minutes, P = .0001) and 9:13 ± 0.55 pm vs 8:26 ± 1.31 pm, P = .003). Parents of children with behavioral insomnia described their childs feeding as “a problem” more frequently compared with controls (26% vs 9%, P = .001 [ES: 0.69]). They reported being more concerned about their childs growth (2.85 ± 1.1 vs 2.5 ± 1.0, P = .03) and reported higher scores of food refusal compared with controls (3.38 ± 0.54 vs 3.23 ± 0.44, P = .04). CONCLUSIONS: Problematic sleep and feeding behaviors tend to coexist in early childhood. Increased awareness of clinicians to this coexistence may allow early intervention and improve outcome.

Oxidative Stress in Children with Obstructive Sleep Apnea Syndrome

STUDY OBJECTIVES Pediatric obstructive sleep apnea (OSA) is associated with cardiovascular consequences, including accelerated atherosclerosis and endothelial dysfunction. Increased lipid peroxidation, a marker of oxidative stress, has been identified in adults with OSA in a severity-dependent manner, with attenuation following treatment with continuous positive airway pressure therapy. Studies on oxidative stress in children with OSA are sparse and results are inconclusive. The objective of this study was to compare lipid peroxidation in children with OSA to non-OSA children. METHODS A prospective cross-sectional study of 26 children with polysomnography-confirmed OSA (oAHI ≥ 5/h TST) was conducted. Thirty age- and body mass index z-score-matched children with primary snoring (PS) served as a comparison group (oAHI ≤ 1/h TST). Fasting blood samples were obtained on the morning following the sleep study. Plasma oxidized low-density lipoprotein (oxLDL) concentrations were measured by enzyme-linked immunosorbent assay. RESULTS There were no group differences in patient characteristics and their lipid profiles. The mean oxLDL levels of the OSA group were significantly higher than those of the comparison group (53.1 ± 13.0 vs. 45.7 ± 10.0 U/L, respectively, p = 0.02). There was a significant positive correlation between plasma oxLDL and the apnea hypopnea index (r = 0.29, p = 0.03) and between oxLDL and the oxygen desaturation index (r = 0.51, p = 0.003), and a significant negative correlation between SpO2 nadir and oxLDL (r = -0.29, p = 0.03). CONCLUSIONS OSA in children is associated with increased lipid peroxidation in a severity-dependent manner. Lipid peroxidation levels correlate with the degree of intermittent hypoxia.