Sleep‐disordered breathing is common among term and near term infants in the NICU

ObjectiveAmong older infants and children, sleep‐disordered breathing (SDB) has negative neurocognitive consequences. We evaluated the frequency and potential impact of SDB among newborns who require intensive care.Study DesignTerm and near‐term newborns at risk for seizures underwent 12‐h attended polysomnography in the neonatal intensive care unit (NICU). Bayley Scales of Infant Development, third edition (Bayley‐III) were administered at 18‐22 months.ResultThe 48 newborns (EGA 39.3 ± 1.6) had a median pediatric apnea‐hypopnea index (AHI) of 10.1 (3.3‐18.5) and most events were central (vs obstructive). Maternal and prenatal factors were not associated with AHI. Moreover, neonatal PSG results were not associated with Bayley‐III scores (P > 0.05).ConclusionSDB is common among term and near‐term newborns at risk for seizures. Follow‐up at ages when more nuanced testing can be performed may be necessary to establish whether neonatal SDB is associated with long‐term neurodevelopmental disability.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149248/1/ppul24266.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149248/2/ppul24266_am.pd

Associations between age and sleep apnea risk among newborn infants

ObjectiveAmong older children, sleep‐disordered breathing (SDB) is associated with measurable neurocognitive consequences. However, diagnostic SDB thresholds are lacking for infants < 12 months. We sought to evaluate the relationship between SDB indices, gestational age (GA), and postmenstrual age (PMA) for infants who underwent clinically‐indicated polysomnograms at a tertiary care center.MethodsEvery infant < 3‐months chronological age whose first clinically‐indicated polysomnogram was between 2/2012 and 2/2017 was included. Linear regression was used to evaluate associations between apnea‐hypopnea index (AHI), obstructive‐apnea index (OAI), and GA and PMA for infants with and without obvious clinical risk factors for SDB (eg, micrognathia and cleft palate).ResultsFor 53 infants without obvious SDB risk factors (GA 35.6 ± 4.5 weeks; PMA 41.2 ± 4.0 weeks), mean AHI was 27 ± 18 and OAI 2.9 ± 4.5. There was a weak inverse relationship between AHI and PMA (r2 = 0.12, P = 0.01), but AHI was not predicted by GA (r2 = 0.04, P = 0.13). Conversely, OAI was more strongly associated with GA (r2 = 0.33, P < 0.0001) than PMA (r2 = 0.08, P = 0.036). For 28 infants with congenital structural anomalies that predispose to SDB (GA 38.0 ± 3.1 weeks, PMA 43.1 ± 3.3 weeks, AHI 37.7 ± 30, OAI 8.2 ± 11.8), neither AHI nor OAI were related to PMA or GA.ConclusionsAmong infants who received clinically‐indicated polysomnograms but did not have obvious structural risk for SDB, AHI declined with advancing PMA, but obstructive‐apnea was best predicted by prematurity. In contrast, the SDB risk did not improve with increasing GA or PMA for infants with congenital structural risk factors; such infants may not outgrow their risk for SDB.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150552/1/ppul24354_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150552/2/ppul24354.pd

Neurodevelopmental Outcomes at Two Years of Age for Premature Infants Diagnosed With Neonatal Obstructive Sleep Apnea

STUDY OBJECTIVES: Neurocognitive deficits have been shown in school-aged children with sleep apnea. The effect of obstructive sleep apnea (OSA) on the neurodevelopmental outcome of preterm infants is unknown. METHODS: A retrospective chart review was performed for all preterm infants ( 1 event/h. Regression analyses were performed to find a relationship between PSG parameters and cognitive, language, and motor scores. RESULTS: Fifteen patients (males: n = 10) were eligible for the study. Median postmenstrual age at the time of the PSG was 41 weeks (37-46). Median AHI for the cohort was 17.4 events/h (2.2-41.3). Median cognitive, language, and motor scores were 90 (65-125), 89 (65-121), and 91 (61-112), respectively. Mean end-tidal CO2 (median 47 mm Hg [25-60]) negatively correlated with cognitive scores (P = .01) but did not significantly correlate with language or motor scores. AHI was not associated with cognitive, language, or motor scores. CONCLUSIONS: The median score for cognitive, language, and motor scores for preterm infants with neonatal OSA were within one standard deviation of the published norm. Mean end-tidal CO2, independent of AHI, may serve as a biomarker for predicting poor cognitive outcome in preterm infants with neonatal OSA

Effects of SIDS risk factors and hypoxia on cardiovascular control in infants

Background and aims. Sudden infant death syndrome (SIDS) is a rare lethal event occurring in 0.1 to 0.3 of infants. In Finland, 10 to 20 infants die from SIDS annually. Research has defined many risk factors for SIDS, but the cascade leading to death remains unexplained. Cardiovascular recordings of infants succumbing to SIDS, as well as animal models, suggest that the final sequelae involve cardiovascular collapse resembling hypotensive shock. There is also evidence of previous hypoxia in SIDS infants. In animal studies, vestibulo-mediated cardiovascular control has been shown to be important in hypotensive shock. Hence, we hypothetized that SIDS victims may have impaired vestibulo-mediated cardiovascular control, possibly due to previous hypoxic episodes. In this thesis, we studied cardiovascular control, and especially vestibulo-mediated cardiovascular control in infants with known risk factors for SIDS at 2 to 4 months of age when the risk for SIDS is highest. Study subjects. A full polysomnographic recording with continuous blood pressure (BP) measurement was performed in 50 infants at 2-4 months of age: 20 control infants, nine infants with univentricular heart (UVH) suffering from chronic hypoxia, 10 infants with bronchopulmonary dysplasia (BPD) with intermittent postnatal hypoxic events, and 11 infants whose mothers had smoked during pregnancy, and thus had been exposed to intrauterine hypoxia and nicotine, were studied. In addition, 20 preterm infants were studied at the gestational age of 34-39 weeks to evaluate developmental aspects of cardiovascular control during head-up tilt test and vestibular stimulus. Methods. Linear side motion and 45° head-up tilt tests were performed in quiet non-rapid eye movement sleep (NREM). Heart rate (HR) and BP responses were analysed from the tests without signs of subcortical or cortical arousal. In addition, HR variability during NREM sleep was assessed. As a general marker of cardiovascular reactivity, HR response to spontaneous arousal from NREM sleep was also evaluated. Results.Side motion test. In the side motion test, control infants presented a biphasic response. First, there was a transient increase in HR and BP. This was followed by a decrease in BP to below baseline, and a return to baseline in HR. All other infant groups showed altered responses. UVH infants and preterm infants near term age had markedly reduced responses. Infants with BPD presented with variable responses: some responded similarly to controls, whereas others showed no initial increase in BP, and the following BP decrease was more prominent. Infants with intrauterine exposure to cigarette smoke showed flat initial BP responses, and the following decrease was more prominent, similarly to a subgroup of BPD infants. Tilt test. Control infants presented with a large variability in BP responses to head-up tilting. On average, systolic BP remained, at first, close to baseline, and diastolic BP increased, after which both decreased and remained below baseline even at the end of the tilt test. On average, HR showed a biphasic response with an initial increase followed by a decrease to below and, finally, a return to baseline. UVH infants showed a similar BP response, but their HR response was tachycardic. Preterm infants with BPD presented with an even greater variability in their BP responses to head-up tilts than control infants, but the overall response as a group did not differ from that of the controls. The tilt response of infants exposed to maternal cigarette smoking during pregnancy did not markedly differ from the control response. Preterm infants near term age showed attenuated responses in both cardiovascular measures, together with greater inter-subject variability compared to the control infants. Discussion. In conclusion, the studied infants with SIDS risk factors showed altered vestibulo-mediated cardiovascular control during the linear side motion test and head-up tilt test. The findings support our initial hypothesis that some infants with SIDS risk factors have defective vestibulo-mediated cardiovascular control, which may lead to death in life-threatening situations.Kätkytkuolemat ovat harvinaisia, mutta ne ovat edelleen suurin yksittäinen syy täysiaikaisena syntyneiden imeväisten kuolemaan. Suomessa kätkytkuolemaan menehtyy vuosittain 10-20 lasta. Kätkytkuoleman syytä ei tiedetä. Epidemiologisten tutkimusten avulla kätkytkuoleman riskitekijät tunnetaan hyvin; näitä ovat mm. vatsallaan nukkuminen, äidin raskaudenaikainen tupakointi ja keskosuus. Selällään nukuttamisen yleistymisen myötä kätkytkuolemien määrä on vähentynyt olennaisesti. Koe-eläintöissä ja muutamassa kätkytkuoleman aikaisessa seurantanauhoituksessa on viitteitä siitä, että kätkytkuoleman mekanismi todennäköisesti muistuttaa verenvuotosokin loppuvaiheen kaltaista verenkiertoelimistön toiminnan romahtamista. Koe-eläintöiden perusteella tällaisessa sokkitilanteessa tasapainotumakevälitteinen verenkierron säätely on tärkeää. Tämän tutkimuskokonaisuuden pääolettaman mukaan kätkytkuolleilla on puutteellinen tasapainotumakevälitteinen sykkeen ja verenpaineen säätely. Koska kätkytkuolleilla on myös todettu merkkejä hapenpuutteesta ennen kuolemaa, voi poikkeavan tasapainotumakevälitteisen verenkierron säätelyn syynä olla edeltänyt hapenpuute: riskiryhmistä esimerkiksi keskosilla lyhytkestoiset hapenpuutejaksot ja äidin raskaudenaikaiselle tupakoinnille altistuneilla lapsilla pitkäaikainen lievä hapenpuute sikiöaikana. Myös pitkäaikaisesta syntymän jälkeisestä hapenpuutteesta kärsivillä yksikammiosydämisillä imeväisillä on todettu äkillisiä, kätkytkuoleman kaltaisia kuolemia. Tutkimme imeväisen verenkierron säätelyä unen aikana rekisteröimällä verenkiertovasteita sivuttaissiirto- ja kippilavatestille täysiaikaisilla imeväisillä sekä imeväisillä, joilla on yllämainittuja kätkytkuoleman riskitekijöitä tai hapenpuutetta. Unirekisteröinti tehtiin yhteensä 70 imeväiselle. 2-4 kuukauden korjatussa iässä tutkittiin 20 täysiaikaista verrokkia, 10 bronkopulmonaalisesta dysplasiasta kärsivää keskosta, 9 yksikammiosydämistä imeväistä sekä 11 imeväistä, joiden äidit tupakoivat raskauden aikana. Lisäksi tutkimme 20 keskosta 34-39 raskausviikon iässä sykkeen ja verenpaineen säätelyn kehityksen kartoittamiseksi. Sivuttaissiirtotesti sekä 45° kippilavatesti pää ylöspäin tehtiin rauhallisessa ei-REM-unessa. Terveiden täysiaikaisten verrokkien verenpaine- ja sykevasteita käytettiin vertailukohtana muiden ryhmien vasteita arvioitaessa. Syke- ja verenpainevasteet arvioitiin testeistä, joissa ei ollut viitettä havahtumisesta tai heräämisestä. Sydämen sykkeen vaihtelevuutta ja spontaanin heräämisen aiheuttamaa sykevastetta käytettiin kuvaamaan yleistä verenkiertoelimistön säätelyn herkkyyttä. Sivuttaissiirtotestissä verrokit reagoivat kaksivaiheisella syke- ja verenpainevasteella. Sekä verenpaine että syke nousivat aluksi, jonka jälkeen verenpaine laski alle lähtötason ennen paluuta lähtötasoon, ja syke palasi lähtötasoon. Muissa tutkituissa ryhmissä vasteet poikkesivat normaalivasteista. Yksikammiosydänlapsilla sekä lähellä laskettua aikaa tutkituilla keskosilla syke- ja verenpainevasteet sivuttaissiirrolle olivat hyvin vaimeat. Puolet bronkopulmonaalisesta dysplasiasta kärsivistä imeväisistä reagoi samoin kuin verrokit, mutta puolella verenpaineen nousu puuttui ja sitä seurannut verenpaineen lasku oli selvästi normaalia syvempi. Myös imeväisillä, joiden äidit olivat tupakoineet raskauden aikana, verenpaineen alkunousu puuttui ja sitä seurannut verenpaineen lasku oli verrokkeja syvempi. Kippilavatestissä täysiaikaisten verrokkien verenpainevasteet olivat hyvin vaihtelevat. Keskimäärin testin alussa systolinen verenpaine pysyi ennallaan ja diastolinen nousi. Testin jatkuessa molemmat laskivat alle lähtötason, jossa ne pysyivät vielä testin lopettamisen jälkeenkin. Verrokkien sykevasteet olivat selkeästi yhtenevämmät ja vaste oli kaksivaiheinen: alun sykkeen nousua seurasi sykkeen lasku alle lähtötason ja paluu takaisin lähtötasoon. Yksikammiosydänlasten verenpainevasteet olivat verrokkien kaltaiset, mutta heidän sykkeensä pysyi korkeana koko testin ajan. Bronkopulmonaalisesta dysplasiasta kärsivien imeväisten verenpainevasteissa oli vielä voimakkaampaa vaihtelua kuin verrokkien vasteissa, mutta ryhmänä heidän vasteensa ei eronnut verrokeista. Raskaudenaikaiselle tupakoinnille altistuneiden imeväisten verenkiertovasteet eivät eronneet verrokeista. Lähellä laskettua aikaa tutkittujen keskosten syke- ja verenpainevasteissa oli suurta vaihtelua verrattuna täysiaikaisiin verrokkeihin, mutta ryhmänä verenkiertovasteet olivat vaimeammat kuin verrokeilla. Tässä tutkimuksessa todettiin poikkeava tasapainotumakevälitteinen verenkierron säätely imeväisillä, joilla on yllämainittuja kätkytkuoleman riskitekijöitä ja edeltäneitä hapenpuutejaksoja. Tutkimustulokset tukevat etukäteisolettamustamme, että heikentynyt tasapainotumakevälitteinen verenkierron säätely imeväisillä voi olla osaltaan johtamassa kätkytkuolemaan henkeä uhkaavassa tilanteessa

Automatic neonatal sleep stage classification:A comparative study

Sleep is an essential feature of living beings. For neonates, it is vital for their mental and physical development. Sleep stage cycling is an important parameter to assess neonatal brain and physical development. Therefore, it is crucial to administer newborn's sleep in the neonatal intensive care unit (NICU). Currently, Polysomnography (PSG) is used as a gold standard method for classifying neonatal sleep patterns, but it is expensive and requires a lot of human involvement. Over the last two decades, multiple researchers are working on automatic sleep stage classification algorithms using electroencephalography (EEG), electrocardiography (ECG), and video. In this study, we present a comprehensive review of existing algorithms for neonatal sleep, their limitations and future recommendations. Additionally, a brief comparison of the extracted features, classification algorithms and evaluation parameters is reported in the proposed study

Sleep and chronotype during pregnancy, and the bright light treatment of perinatal depression

Background Perinatal depression (PND) is a severe mental disorder with disruptive consequences on the health and well-being of mothers, children, and their families. Due to the induced socioeconomic burden, it also represents a major public health problem for society as a whole, and is therefore considered a priority target of health prevention strategies at a global level. There is, in fact, general consensus among experts that PND is still prevalent, underrecognized and undertreated. While research on the pathophysiological mechanisms of PND is contributing to an increased knowledge of the multifactorial causes of this condition, and is likely to provide new biomarkers for medical use in the near future, none of these is currently available for the everyday clinical practice. Conversely, there is an urgent need of easy and universal screening instruments, as well as safe and affordable treatments that all women can have access to. Sleep and circadian rhythm disruption are commonly experienced by women during the perinatal period, but there is limited evidence on the objective changes in sleep parameters occurring during pregnancy and how these relate to health outcomes. Moreover, the role of sleep and circadian factors in the etiology of PND and as potential targets for treatment is still underestimated and underinvestigated. As an example, the influence of different circadian preferences for sleep-wake times (chronotypes) on the development of depressive symptoms across the perinatal period has never been investigated. Likewise, the efficacy and safety of bright light therapy (BLT) for the treatment of PND with onset before and/or after delivery have never been tested. Objectives Manuscript 1: to perform the first systematic review and meta-analysis of polysomnographic studies during pregnancy, in order to identify possible objective markers of sleep disruption in pregnant women. Manuscript 2: to investigate whether chronotype is a risk factor for PND and to explore the association between chronotype, maternal sociodemographic characteristics, and lifestyle habits, in relation to PND. Manuscript 3: to conduct the first randomized controlled trial (RCT) aimed at testing the efficacy and safety of BLT for PND occurring over a 12-month observation period. Methods Manuscript 1: by carefully following the PRISMA guidelines, we conducted the first systematic review of polysomnographic studies during pregnancy available in the literature. In addition, we performed a meta-analysis of the data collected on two sleep variables (TST and SE). This was instead not possible for other sleep parameters, due to the large heterogeneity of the reviewed studies. Manuscript 2: as a part of the “Life-ON” project, a multicenter, prospective, cohort study on sleep and mood changes during the perinatal period, 299 women were followed-up from the first trimester of pregnancy until 6 months postpartum. Chronotype was assessed at baseline using the MEQ, while mood was repeatedly evaluated at several timepoints with depression rating scales (i.e., EPDS, HDRS, and MADRS). The influence of time and chronotype on the different scales was estimated by constructing multilevel linear mixed regression models. A Cox proportional-hazard regression model was built to evaluate the association between chronotype and incidence of depression. Manuscript 3: in the frame of the “Life-ON” project, a RCT was conducted in a subsample of women with an EPDS score >12 at any time point from the second trimester of pregnancy up to 6 months postpartum. Participants received either BLT (10’000 lux) or DRL (19 lux) for 6 weeks, 30 minutes in the morning, within 20 minutes after wake up, and at a distance of 30 cm from the light box. Multilevel linear models were constructed to test for the influence of time and treatment group on EPDS values and log-linear models to test for socioeconomic factors influencing PND remission. Results According to our systematic review, the main changes in objective sleep parameters during pregnancy consists in a reduction of sleep duration and a fragmentation of sleep continuity, with an increased number of awakenings and superficial sleep stages (N1, N2), and a simultaneous decrease of SWS, REM sleep, and SE. The meta-analysis revealed a significant reduction of TST by 26.8 min between the first and third trimester of pregnancy, as well as a decrease of SE by 4% within the same time frame. Pregnant evening chronotypes, as compared to the other chronotypes, are more vulnerable to PND symptoms, especially in the immediate postpartum period. Although the survival analysis did not show a statistically significant influence of chronotype on the overall risk of PND, a trend towards an increased risk for PND in evening chronotypes and a reduced risk in intermediate types, as compared to morning types, was observed. Furthermore, in line with the literature, pregnant women with evening chronotype in the Life-ON study were more likely subject to health problems and negative pregnancy outcomes than the other chronotypes, and presented adverse sociodemographic characteristics and lifestyle attitudes, that are commonly associated with a higher risk for PND. Finally, in a RCT testing 6-week morning BLT (10’000 lux) vs. DRL (19 lux) for treating PND, the active light intervention (BLT) showed a remarkable efficacy in inducing a rapid remission from PND compared to DRL. The multilevel linear model revealed a significant influence of time on EPDS score and a group-time interaction, with a greater and sustained reduction in the BLT-group across the whole follow-up period. Conclusion We found evidence that the subjective experience of sleep deterioration, that many women report during pregnancy, is related to objective alterations in sleep architecture, particularly during late gestation. These can only be appropriately recorded by PSG, which should be therefore considered a valuable and sometimes necessary instrument to correctly diagnose sleep disorders, also during pregnancy, by overcoming under- or overestimation bias due to subjective reports of sleep problems. Interestingly, despite several physiological factors may be involved in the subjective worsening of sleep quality across gestation, is not pregnancy per se, that causes major PSG-assessed sleep disorders in healthy, normal-weight women. Rather, it is likely the combination of predisposing factors, such as obesity, higher maternal age or hypertension, and physiological changes occurring during pregnancy, that may contribute in particular to the development of obstructive sleep apnea (OSA) in at-risk pregnant women. Evening chronotype is associated with a time-dependent, greater severity of PND. Thus, assessing chronotype during pregnancy via the administration of an easy screening questionnaire, may help identify women who are likely to experience more severe perinatal depressive symptoms, especially in the early postpartum, and provide them with psychiatric/psychological support and treatment. BLT can not only induce a rapid and significant remission from PND compared to DRL, but the resulting improvement in mood can be maintained over time after treatment completion. These new findings support the integration of BLT as effective and safe chronotherapeutic tool, based on solid scientific evidence, to the equipment available to clinicians for the treatment of PND, thus responding to the need for affordable, easy-to-use, and accessible therapies for patients

Sleep, sleep-disordered-breathing : cognition and prematurity

Tese de doutoramento, Medicina (Psiquiatria e Saúde Mental), Universidade de Lisboa, Faculdade de Medicina, 2018Prematurity leads to many handicaps, some of them are only recognized later in life and may impact the individuals for the rest of their life. The delivery date compared to the full term delivery time will be a measure of “indication of risks” of post-natal handicap risk, but this is only one of the many measurements that can be looked at. Many studies have investigated development of premature infants, based on different criteria at entry in the considered study. Our investigations are only a limited contribution to the investigation of premature infants. We included infants born as young as 24 weeks of gestational-age [GA] but none of the infants had major neurological syndromes recognized at birth. “Normal infants” defined as infants with more than 37 weeks of GA, birth-weight >2500g and absence of any indication of health problems born in the same hospital maternity at same time as premature infants were also recruited to serve as normal controls. As most newborn infants spend a large amount of time asleep, all the presented studies include investigation of sleep, and once sleep-time occurred mostly during the nocturnal period, it focused on the polygraphic monitoring of the nocturnal sleep. The premature cohort study was a longitudinal study and parents who signed informed consent approved by the Chang Gung Hospital and Medical College Ethic Committee, were asked to come back on a yearly basis for at least 5 years. This is an on-going study and not every child has been followed for such time. Furthermore, as in any longitudinal study, loss of patients occurred as parents did not bring children back. At entry 400 parents signed the informed consent, currently at 5 years follow-up 150 children have ended the follow-up period and about 215 at 4 years. The sample is a non-random convenience sample of children selected based on the parents` willingness to participate in the protocol and obtained with the help of neonatologist physicians in our NICUs. Most of the studies presented in the thesis come-out of this longitudinal study. The studies asked specific questions, particularly looking at development of abnormal obstructive breathing during sleep. But some of our studies looked also at children of older age as some of the findings that we observed in our premature cohort needed a different investigative approach, and prior validation on older children-premature and in non-premature infants. We have included these studies in our narrative as they become part of our research, and they are part of a general research program on “sleep- breathing-and-cognition” in children

A One-Hour Sleep Restriction Impacts Brain Processing in Young Children Across Tasks: Evidence From Event-related Potentials

The effect of mild sleep restriction on cognitive functioning in young children is unclear, yet sleep loss may impact children\u27s abilities to attend to tasks with high processing demands. In a preliminary investigation, six children (6.6 - 8.3 years of age) with normal sleep patterns performed three tasks: attention (“Oddball”), speech perception (conconant-vowel syllables) and executive function (Directional Stroop). Event-related potentials (ERP) responses were recorded before (Control) and following one-week of 1-hour per day of sleep restriction. Brain activity across all tasks following Sleep Restriction differed from activity during Control Sleep, indicating that minor sleep restriction impacts children\u27s neurocognitive functioning

Automatic neonatal sleep stage classification: A comparative study

Sleep is an essential feature of living beings. For neonates, it is vital for their mental and physical development. Sleep stage cycling is an important parameter to assess neonatal brain and physical development. Therefore, it is crucial to administer newborn's sleep in the neonatal intensive care unit (NICU). Currently, Polysomnography (PSG) is used as a gold standard method for classifying neonatal sleep patterns, but it is expensive and requires a lot of human involvement. Over the last two decades, multiple researchers are working on automatic sleep stage classification algorithms using electroencephalography (EEG), electrocardiography (ECG), and video. In this study, we present a comprehensive review of existing algorithms for neonatal sleep, their limitations and future recommendations. Additionally, a brief comparison of the extracted features, classification algorithms and evaluation parameters is reported in the proposed study