Study protocol: assessing SleeP IN infants with early-onset atopic Dermatitis by Longitudinal Evaluation (The SPINDLE study)

Cathal O'Connor, Alan D Irvine, Deirdre Murray, Michelle Murphy, Jonathan O'B Hourihane, Geraldine Boylan, Cathal O'Connor, Alan D Irvine, Deirdre Murray, Michelle Murphy, Jonathan O'B Hourihane, Geraldine Boylan

Abstract

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin condition in childhood. Most (50-60%) children with AD report sleep disturbance, which is secondary to itch, dry skin, inflammation, and abnormal circadian rhythm. Sleep is essential for brain development, learning, and growth. Sleep disruption in early life is associated with cognitive and psychological dysfunction in later life. The aim of this study is to describe in detail the sleep architecture of infants with early-onset atopic dermatitis (AD), compared to controls, by using EEG polysomnography, sleep actigraphy, and parental reporting.

Methods: This observational study will recruit six- to eight-month old infants with moderate to severe AD and age-matched control infants who do not have AD. At six-eight months diurnal sleep electroencephalography and polysomnography will be performed in our research center. Nocturnal sleep actigraphy will be performed at home for five consecutive nights at six-eight months and 12 months. Between six and 12 months, monthly questionnaires will capture data on quantitative sleep and parental sleep. Skin barrier and immune profiles will be captured at six-eight and 12 months. AD will be assessed using standardized severity assessment tools and treated according to protocol. A neurodevelopmental assessment will be performed at 18 months to assess cognition and behaviour. An estimated sample size of 50 participants in each group is required to power the primary outcome of disturbed macrostructure of sleep and secondary outcomes of disturbed microstructure of sleep, and disturbed parental sleep, assuming an attrition rate of 60%. Potential confounding factors which will be controlled for in the data analysis will include parental educational level, parental depression, feeding practice, and number of siblings.

Discussion: This study will provide a rich analysis of sleep in infants with AD in the first year of life using detailed electroencephalography, novel actigraphy techniques, and longitudinal parent-reported data. It may provide guidance on the optimal treatment of AD to prevent or reduce sleep disruption.

Trial registration: clinicaltrials.gov NCT05031754 , retrospectively registered on September 2nd, 2021.

Keywords: Actigraphy; Atopic dermatitis; Early intervention; Electroencepalography; Parental sleep disruption; Sleep; Sleep diaries; Sleep disruption.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Data from the ENRICH study showing sleep spindles in a 4-month-old infant. Sleep spindles highlighted in red
Fig. 2
Fig. 2
SPINDLE study flow diagram. EEG = electroencephalogram
Fig. 3
Fig. 3
Sampling of inflammatory cytokines from the stratum corneum by tape stripping
Fig. 4
Fig. 4
Sleep pants with belt to attach sensor device for overnight actigraphy

References

    1. O'Connor C, Kelleher M, O'B Hourihane J. Calculating the effect of population-level implementation of the learning early about Peanut allergy (LEAP) protocol to prevent peanut allergy. J Allergy Clin Immunol. 2016;137(4):1263–1264.e2. doi: 10.1016/j.jaci.2015.11.029.
    1. Wadonda-Kabondo N, Sterne JA, Golding J, et al. Association of parental eczema, hayfever, and asthma with atopic dermatitis in infancy: birth cohort study. Arch Dis Child. 2004;89(10):917–921. doi: 10.1136/adc.2003.034033.
    1. Ständer S. Atopic dermatitis. N Engl J Med. 2021;384(12):1136–1143. doi: 10.1056/NEJMra2023911.
    1. Paller A, Jaworski JC, Simpson EL, et al. Major comorbidities of atopic dermatitis: beyond allergic disorders. Am J Clin Dermatol. 2018;19(6):821–838. doi: 10.1007/s40257-018-0383-4.
    1. Adamson AS. The economics burden of atopic dermatitis. Adv Exp Med Biol. 2017;1027:79–92. doi: 10.1007/978-3-319-64804-0_8.
    1. Silverberg JI, Gelfand JM, Margolis DJ, et al. Patient burden and quality of life in atopic dermatitis in US adults: a population-based cross-sectional study. Ann Allergy Asthma Immunol. 2018;121(3):340–347. doi: 10.1016/j.anai.2018.07.006.
    1. Beattie PE, Lewis-Jones MS. A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases. Br J Dermatol. 2006;155(1):145–151. doi: 10.1111/j.1365-2133.2006.07185.x.
    1. Gruber R, Carrey N, Weiss SK, et al. Position statement on pediatric sleep for psychiatrists. J Can Acad Child Adolesc Psychiatry. 2014;23(3):174–195.
    1. Rasch B, Born J. About sleep's role in memory. Physiol Rev. 2013;93(2):681–766. doi: 10.1152/physrev.00032.2012.
    1. Mirmiran M. The importance of fetal/neonatal REM sleep. Eur J Obstet Gynecol Reprod Biol. 1986;21(5-6):283–291. doi: 10.1016/0028-2243(86)90006-7.
    1. Mirmiran M, Scholtens J, van de Poll NE, Uylings HB, van der Gugten J, Boer GJ. Effects of experimental suppression of active (REM) sleep during early development upon adult brain and behavior in the rat. Brain Res. 1983;283(2-3):277–286. doi: 10.1016/0165-3806(83)90184-0.
    1. Morrissey MJ, Duntley SP, Anch AM, Nonneman R. Active sleep and its role in the prevention of apoptosis in the developing brain. Med Hypotheses. 2004;62(6):876–879. doi: 10.1016/j.mehy.2004.01.014.
    1. Liu D, Diorio J, Day JC, Francis DD, Meaney MJ. Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nat Neurosci. 2000;3(8):799–806. doi: 10.1038/77702.
    1. Mulder TA, Kocevska D, Muetzel RL, et al. Childhood sleep disturbances and white matter microstructure in preadolescence. J Child Psychol Psychiatry. 2019;60(11):1242–1250. doi: 10.1111/jcpp.13085.
    1. Scher A. Infant sleep at 10 months of age as a window to cognitive development. Early Hum Dev. 2005;81(3):289–292. doi: 10.1016/j.earlhumdev.2004.07.005.
    1. Hon KL, Leung TF, Wong KY, Chow CM, Chuh A, Ng PC. Does age or gender influence quality of life in children with atopic dermatitis? Clin Exp Dermatol. 2008;33(6):705–709. doi: 10.1111/j.1365-2230.2008.02853.x.
    1. Chamlin SL, Mattson CL, Frieden IJ, et al. The price of pruritus: sleep disturbance and cosleeping in atopic dermatitis. Arch Pediatr Adolesc Med. 2005;159(8):745–750. doi: 10.1001/archpedi.159.8.745.
    1. Camfferman D, Kennedy JD, Gold M, Martin AJ, Lushington K. Eczema and sleep and its relationship to daytime functioning in children. Sleep Med Rev. 2010;14(6):359–369. doi: 10.1016/j.smrv.2010.01.004.
    1. Ricci G, Bendandi B, Bellini F, Patrizi A, Masi M. Atopic dermatitis: quality of life of young Italian children and their families and correlation with severity score. Pediatr Allergy Immunol. 2007;18(3):245–249. doi: 10.1111/j.1399-3038.2006.00502.x.
    1. Yu SH, Attarian H, Zee P, Silverberg JI. Burden of sleep and fatigue in US adults with atopic dermatitis. Dermatitis. 2016;27(2):50–58. doi: 10.1097/DER.0000000000000161.
    1. Choi JH, Nam GE, Kim DH, Lee JY, Han KD, Cho JH. Association between sleep duration and the prevalence of atopic dermatitis and asthma in young adults. Asian Pac J Allergy Immunol. 2017;35(3):150–155. doi: 10.12932/AP0772.
    1. Kong TS, Han TY, Lee JH, Son SJ. Correlation between severity of atopic dermatitis and sleep quality in children and adults. Ann Dermatol. 2016;28(3):321–326. doi: 10.5021/ad.2016.28.3.321.
    1. Lewis-Jones S. Quality of life and childhood atopic dermatitis: the misery of living with childhood eczema. Int J Clin Pract. 2006;60(8):984–992. doi: 10.1111/j.1742-1241.2006.01047.x.
    1. Chang YS, Chiang BL. Mechanism of sleep disturbance in children with atopic dermatitis and the role of the circadian rhythm and melatonin. Int J Mol Sci. 2016;17(4):462. doi: 10.3390/ijms17040462.
    1. Chang YS, Chiang BL. Sleep disorders and atopic dermatitis: a 2-way street? J Allergy Clin Immunol. 2018;142(4):1033–1040. doi: 10.1016/j.jaci.2018.08.005.
    1. Fishbein AB, Vitaterna O, Haugh IM, et al. Nocturnal eczema: review of sleep and circadian rhythms in children with atopic dermatitis and future research directions. J Allergy Clin Immunol. 2015;136(5):1170–1177. doi: 10.1016/j.jaci.2015.08.028.
    1. Reuveni H, Chapnick G, Tal A, Tarasiuk A. Sleep fragmentation in children with atopic dermatitis. Arch Pediatr Adolesc Med. 1999;153(3):249–253. doi: 10.1001/archpedi.153.3.249.
    1. Meltzer LJ, Booster GD. Sleep disturbance in caregivers of children with respiratory and atopic disease. J Pediatr Psychol. 2016;41(6):643–650. doi: 10.1093/jpepsy/jsw016.
    1. Ramirez FD, Chen S, Langan SM, et al. Assessment of sleep disturbances and exhaustion in mothers of children with atopic dermatitis. JAMA Dermatol. 2019;155(5):556–563. doi: 10.1001/jamadermatol.2018.5641.
    1. Sette S, Baumgartner E, Ferri R, Bruni O. Predictors of sleep disturbances in the first year of life: a longitudinal study. Sleep Med. 2017;36:78–85. doi: 10.1016/j.sleep.2017.04.015.
    1. Mindell JA, Leichman ES, Composto J, Lee C, Bhullar B, Walters RM. Development of infant and toddler sleep patterns: real-world data from a mobile application. J Sleep Res. 2016;25(5):508–516. doi: 10.1111/jsr.12414.
    1. Van de Water AT. Holmes A, Hurley DA. Objective measurements of sleep for non-laboratory settings as alternatives to polysomnography--a systematic review. J Sleep Res. 2011;20(1 Pt 2):183–200. doi: 10.1111/j.1365-2869.2009.00814.x.
    1. Doucette MR, Kurth S, Chevalier N, Munakata Y, LeBourgeois MK. Topography of Slow Sigma Power during Sleep is Associated with Processing Speed in Preschool Children. Brain Sci. 2015;5(4):494–508. doi: 10.3390/brainsci5040494.
    1. Ujma PP, Sándor P, Szakadát S, Gombos F, Bódizs R. Sleep spindles and intelligence in early childhood-developmental and trait-dependent aspects. Dev Psychol. 2016;52(12):2118–2129. doi: 10.1037/dev0000233.
    1. Romanos M, Gerlach M, Warnke A, Schmitt J. Association of attention-deficit/hyperactivity disorder and atopic eczema modified by sleep disturbance in a large population-based sample. J Epidemiol Community Health. 2010;64(3):269–273. doi: 10.1136/jech.2009.093534.
    1. Irvine AD, McLean WH, Leung DY. Filaggrin mutations associated with skin and allergic diseases. N Engl J Med. 2011;365(14):1315–1327. doi: 10.1056/NEJMra1011040.
    1. Kelleher MM, O'Carroll M, Gallagher A, et al. Newborn transepidermal water loss values: a reference dataset. Pediatr Dermatol. 2013;30(6):712–716. doi: 10.1111/pde.12106.
    1. Ní Chaoimh C, Nico C, Puppels GJ, et al. In vivo Raman spectroscopy discriminates between FLG loss-of-function carriers vs wild-type in day 1-4 neonates. Ann Allergy Asthma Immunol. 2020;124(5):500–504. doi: 10.1016/j.anai.2020.01.022.
    1. Nemoto-Hasebe I, Akiyama M, Nomura T, Sandilands A, McLean WH, Shimizu H. Clinical severity correlates with impaired barrier in filaggrin-related eczema. J Invest Dermatol. 2009;129(3):682–689. doi: 10.1038/jid.2008.280.
    1. Kezic S, O'Regan GM, Yau N, et al. Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity. Allergy. 2011;66(7):934–940. doi: 10.1111/j.1398-9995.2010.02540.x.
    1. Guttman-Yassky E, Diaz A, Pavel AB, et al. Use of tape strips to detect immune and barrier abnormalities in the skin of children with early-onset atopic dermatitis [published online ahead of print, 2019 Oct 9] JAMA Dermatol. 2019;155(12):1358–1370. doi: 10.1001/jamadermatol.2019.2983.
    1. McAleer MA, Jakasa I, Hurault G, et al. Systemic and stratum corneum biomarkers of severity in infant atopic dermatitis include markers of innate and T helper cell-related immunity and angiogenesis. Br J Dermatol. 2019;180(3):586–596. doi: 10.1111/bjd.17088.
    1. Buysse DJ, Reynolds CF, 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213. doi: 10.1016/0165-1781(89)90047-4.
    1. Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol (Stockh) 1980;Suppl 92:44–47.
    1. Chopra R, Vakharia PP, Sacotte R, et al. Severity strata for eczema area and severity index (EASI), modified EASI, Scoring atopic dermatitis (SCORAD), objective SCORAD, atopic dermatitis severity index and body surface area in adolescents and adults with atopic dermatitis. Br J Dermatol. 2017;177(5):1316–1321. doi: 10.1111/bjd.15641.
    1. Chopra R, Silverberg JI. Assessing the severity of atopic dermatitis in clinical trials and practice. Clin Dermatol. 2018;36(5):606–615. doi: 10.1016/j.clindermatol.2018.05.012.
    1. Gaunt DM, Metcalfe C, Ridd M. The patient-oriented eczema measure in young children: responsiveness and minimal clinically important difference. Allergy. 2016;71(11):1620–1625. doi: 10.1111/all.12942.
    1. Haydek CG, Love E, Mollanazar NK, et al. Validation and banding of the ItchyQuant: a self-report itch severity scale. J Invest Dermatol. 2017;137(1):57–61. doi: 10.1016/j.jid.2016.06.633.
    1. Lewis-Jones MS, Finlay AY, Dykes PJ. The Infants' dermatitis quality of life index. Br J Dermatol. 2001;144(1):104–110. doi: 10.1046/j.1365-2133.2001.03960.x.
    1. Dodington SR, Basra MK, Finlay AY, Salek MS. The dermatitis family impact questionnaire: a review of its measurement properties and clinical application. Br J Dermatol. 2013;169(1):31–46. doi: 10.1111/bjd.12232.
    1. NICE. Postnatal care up to 8 weeks after birth. Available from: .
    1. O’ Toole J, Boylan G. Neural: quantitative features for newborn EEG using Matlab. arXiv e-prints. 2017;arXiv:1704.05694 [physics.med-ph].
    1. Twomey DM, Ahearne C, Hennessy E, et al. Concurrent validity of a touchscreen application to detect early cognitive delay [published online ahead of print, 2020 Sep 18]. Arch Dis Child. 2020;archdischild-2019-318262. doi:10.1136/archdischild-2019-318262
    1. Burnham MM, Goodlin-Jones BL, Gaylor EE, Anders TF. Nighttime sleep-wake patterns and self-soothing from birth to one year of age: a longitudinal intervention study. J Child Psychol Psychiatry. 2002;43(6):713–725. doi: 10.1111/1469-7610.00076.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe