Does melatonin improve sleep and functioning in children with Fetal Alcohol Spectrum Disorder? A comparison with placebo.

INTERVENTION: Prior to receiving medication treatments, parents/carers will also receive basic sleep hygiene information via an information sheet and a brief interview with a researcher (approx 15 mins) to implement for two weeks. The sleep hygiene information will cover basic behavioral routine tips and environmental issues that can affect sleep quality that have been readily designed specifically for this study. If the study child's sleep is still disturbed after this period (ie over this period they still meet criteria), they will be entered into the melatonin/placebo treatment phase. Across a 6 week cross‐over trial, children will receive sublingual liquid melatonin for a three week period and a placebo for a three week period. The order of these treatment periods will be randomised per participant. Children will be prescribed a dose of 0.1 mg of melatonin per kilogram of body weight, with a maximum dose of 6 mg. Because melatonin has a short halflife, there will be no wash out period. However, analysis after the trial may exclude the first 1‐3 days of data collected from participants in the placebo phase who had previously been in the melatonin phase in an effort to minimise any carry‐over effects. Participants will record their melatonin use in a sleep diary. Products will also be returned and weighed at the end of the trial. CONDITION: Chronic Insomnia Disorder;Fetal Alcohol Spectrum Disorder; Delayed Sleep‐Wake Phase Disorder; ; Chronic Insomnia Disorder ; Fetal Alcohol Spectrum Disorder ; Delayed Sleep‐Wake Phase Disorder Mental Health ‐ Other mental health disorders Reproductive Health and Childbirth ‐ Fetal medicine and complications of pregnancy PRIMARY OUTCOME: Sleep behaviour measured using a sleep diary and actigraphy[Daily for 9 weeks.] SECONDARY OUTCOME: An adaption of the Dimensional Change Card Sort Task (DCCS) will be used as a direct behavioural measure of set shifting ability, also referred to as cognitive flexibility executive function (Zelazo et al., 2013). The task will be presented on a computer. Participants are presented with two stimuli at the bottom of a screen that each have a different shape and colour dimension. They are asked to sort stimuli that subsequently appear on the screen by either the shape or colour dimension by pressing the response button that represents the corresponding dimension. Across multiple blocks the dimension that they are asked to sort stimuli by changes. Performance is measured using accuracy and response times. The DCCS task has high internal reliability, ICC = .92, and converges with scores on the WPPSI‐III Block Design task, r = .69, in 3‐8 year olds (Zelazo et al., 2013). On each assessment occasion, a different arrangement of trial types and stimuli will be used to minimise practice effects.[Measured baseline, post sleep hygeine (week 3), halfway through treatment phase (week 6), and end of treatment phase (week 9)] Child Behavioural Functioning using the BRIEF[Measured baseline, post sleep hygeine (week 3), halfway through treatment phase (week 6), and end of treatment phase (week 9)] Motor inhibitory control will be measured using a stop‐signal paradigm. Participants will be shown stimuli that they will have to respond to as quickly as possible. Occasionally, immediately after the presentation of target stimuli they will be presented with stimuli signalling that they should stop their response (stop trials). Their ability to terminate their response before pressing a button on a keyboard on stop trials will be used as a measure of inhibitory control. This task is commonly used in paediatric populations and has been used extensively as an outcome measure in trials involving young children with neurodevelopmental difficulties (Soreni, Crosbie, Ickowicz, & Schachar, 2009). On each assessment occasion, a different arrangement of trial types and stimuli will be used to minimise practice effects.[Measured baseline, post sleep hygeine (week 3), halfway through treatment phase (week 6), and end of treatment phase (week 9)] Parent Stress Index[Measured baseline, post sleep hygeine (week 3), halfway through treatment phase (week 6), and end of treatment phase (week 9)] Parental stress will be measured using the Parenting Stress Index short form (PSI‐SF), which is a well validated self‐report measure comprising 36 items measured using a five‐point Likert scale of perceived stress in the parenting role (Reitman, Currier, & Stickle, 2002). The three subscales are Parental Distress, Parent‐Child Dysfunctional Interaction, and Difficult Child. PSI‐SF scores are highly stable over a 1‐year period, rs = .61‐.75 (Haskett, Ahern, Ward, & Allaire, 2006) and are internally consistent, as = .74‐.88 (Haskett et al., 2006). PSI‐SF subscale scores map on highly to other measures of parental well‐being and parent‐child relationship quality (Haskett et al., 2006; Reitman et al., 2002). Parents will fill out the Parenting Stress Index short form at the end of every study phase during each scheduled visit. This assessment will be administered during each home visit from the beginning of the treatment phase.[Measured baseline, post sleep hygeine (week 3), halfway through treatment phase (week 6), and end of treatment phase (week 9)] Processing speed will be measured using an adaption of a simple reaction time paradigm (Carlozzi, Tulsky, Kail, & Beaumont, 2013). Children will be presented with a series of stimuli on a computer screen with varying temporal intervals and they will be required to make speeded responses on a keyboard based on appearance of the stimuli (i.e., respond as soon as it appears), and basic categorical information (e.g., similarity judgement based on colour or size). Performance will be measured using response times to stimuli and accuracy of responses. Stimuli will include age‐appropriate pictures of familiar animals and plants (e.g., kangaroo, emu, fish, tree, flower) and symbols (e.g., plus and cross signs). On each assessment occasion, a different arrangement of trial types and stimuli will be used to minimise practice effects.[Measured baseline, post sleep hygeine (week 3), halfway through treatment phase (week 6), and end of treatment phase (week 9)] The NIH Toolbox flanker task will be used as a direct behavioural measure of inhibitory control, which is a component of executive functioning (Zelazo et al., 2013). The task is presented on an electronic tablet and thus test administration and scoring is also standardised. In this task, there are two blocks, one where the visual stimuli are cartoon fish and another where they are arrows. On each trial, participants are presented with four flanker stimuli, two either side of the middle, and then one stimulus in the centre. They are asked to indicate the direction of the central stimulus, which can either be congruent or incongruent with the direction of the flankers, on the touch screen. Performance is measured using response time and accuracy. The NIH Toolbox measures have been normed on people aged 3‐ 85 years. The flanker task shows high internal reliability, ICC = .92, and converges with scores on the WPPSI‐III Block Design task, r = .60, in 3‐8 year olds (Zelazo et al., 2013). This task will be administered during each home visit from the beginning of the treatment phase.[Measured baseline, post sleep hygeine (week 3), halfway through treatment phase (week 6), and end of treatment phase (week 9)] Working memory will be measured using an adaption of a working memory paradigm. They will be presented with a series of stimuli on a computer screen and will be asked to memorise these stimuli for recall using the keyboard. Performance will be measured using accuracy of responses. Similar computerized tasks with age‐appropriate stimuli have been shown to have satisfactory validity and test‐retest reliabilities (Van de Weijer‐Bergsma, Kroesbergen, Prast, & Van Luit, 2015). On each assessment occasion, a different arrangement of trial types and stimuli will be used to minimise practice effects.[Measured baseline, post sleep hygeine (week 3), halfway through treatment phase (week 6), and end of treatment phase (week 9)] INCLUSION CRITERIA: Children aged between 5‐ and 8‐years with confirmed prenatal alcohol exposure and who have been assessed using the Australian Guidelines for the diagnosis of FASD to have either FASD with 3 Sentinel Facial Features (SFF); FASD with < 3 SFF or “At Riskâ€� of FASD (Bower & Elliott, 2016), and with reported sleep problems (see Sleep Inclusion Criteria). Sleep Problem Inclusion Criteria Children will be included in the study if their parents/caregivers report that they have problems with sleep initiation, whereby sleep onset latency is equal to or greater than 45 minutes, three nights or more a week, for equal to or more than a month.