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Joint observation in NICU (JOIN): study protocol of a clinical randomised controlled trial examining an early intervention during preterm care

Introduction Preterm birth may generate significant distress among the parents, who often present with difficulties in appropriating their parental role. Parental stress and low perceived parental self-efficacy may interfere with the infant’s socioemotional and cognitive development, particularly through disrupted parent–infant interactions. Perceived parental self-efficacy represents the belief of efficacy in caring for one’s own infant and successful incarnation of the parental role, as well as the perception of one’s own abilities to complete a specified task. Interventions to support parental role, as well as infant development, are needed, and parental self-efficacy represents a useful indicator to measure the effects of such early interventions. Methods and analysis This study protocol describes a randomised controlled trial that will test an early intervention in the neonatal intensive care unit (NICU) (JOIN: Joint Observation In Neonatology) carried out by an interdisciplinary staff team. Mothers of preterm neonates born between 28 and 32 6/7 weeks of gestational age are eligible for the study. The intervention consists of a videotaped observation by a clinical child psychologist or child psychiatrist and a study nurse of a period of care delivered to the neonate by the mother and a NICU nurse. The care procedure is followed by an interactive video guidance intended to demonstrate the neonate’s abilities and resources to his parents. The primary outcome will be the difference in the perceived maternal self-efficacy between the intervention and control groups assessed by self-report questionnaires. Secondary outcomes will be maternal mental health, the perception of the parent– infant relationship, maternal responsiveness and the neurodevelopment of the infant at 6 months corrected age. Ethics and dissemination Ethical approval was granted by the Human Research Ethics Committee of the Canton de Vaud (study number 496/12). Results from this study will be disseminated at national and international conferences, and in peer-reviewed journals. Trial registration number NCT02736136, Pre-results.


Methods and analysis
This study protocol describes a randomized controlled trial that will test an early intervention in the NICU (JOIN: Joint Observation In Neonatology) carried out by an interdisciplinary staff team. Mothers of preterm neonates born between 28 and 32 6/7 weeks of gestational age are eligible for the study. The intervention consists of a videotaped observation by a clinical child psychologist or psychiatrist and a study nurse of a period of care delivered to the neonate by the mother and a NICU nurse. The care procedure is followed by an interactive video guidance intended to reinforce parental competences and perceived self-efficacy, and to demonstrate the neonate's abilities and resources to his parents.
The primary outcome will be the difference in the perceived maternal self-efficacy between the intervention and control groups assessed by self-reported questionnaires. Secondary outcomes will be the maternal mental health, the perception of the parent-infant relationship, the maternal responsiveness, and the neurodevelopment of the infant at 6 months corrected age.

Ethics and dissemination
Ethical approval was granted by the Human Research Ethics Committee of the Canton de Vaud (study number 496/12). Results from the study will be disseminated at national and international conferences, and in peer-reviewed journals.

Advances in Neonatal Care
Improvement of pre-and postnatal care over the past decades has led to increased survival of very preterm neonates born less than 32 weeks' gestation 1 . Among others, protective measures to promote health and subsequent neurodevelopment have been developed, including optimization of nutritional support, better characterization of neonatal stress, and improved pain management. In the same perspective, developmental care was introduced in the Neonatal Intensive Care Units (NICU) since the 90's with the intention of minimizing the adverse consequences of prematurity on the developing brain. During a critical period of development, the preterm brain is highly vulnerable to injury, represented by cerebral haemorrhage and insult to the white matter. Additionally, beyond the injury, preterm neonates are prone to alteration of brain maturation with disruption of normal developmental trajectory of both grey and white matters [2][3][4] .

Developmental Care
Over the last two decades, a growing body of research focused on the impact of excessive stimuli such as sound, light, touch or pain on the preterm neonate, hypothesizing that an unfavourable and stressful environment may add to the adverse effects of neonatal morbidity 5 . These concerns led progressively to the introduction of developmental care, which consists of individualized strategies mainly based on the neonate's skills and/or difficulties 6 , and supporting the neonate's regulation and development. The first aim of the developmental care is to limit exposure to deleterious environmental stimulations.
Management of sensorial dystimulation, as well as of pain and stress during invasive care procedures, represents a central target of developmental care 7 8 . The second main objective focuses on the child's well-being through the adaptation of the sensorial environment in order to provide more physiological external stimuli (tactile, auditory, visual, vestibular), that will help to promote behaviours and postures fostering comfort and regulation. The third objective of the developmental care aims to support parents in their role and to strengthen the relationship they are developing with their child 7 9 . Although studies have found contradictory results [10][11][12] , some evidence shows a positive impact of developmental care on short-and long-term neonatal and neurodevelopmental outcomes [13][14][15][16] .

Impact of prematurity on parents' well-being
Preterm birth and caring for a preterm infant may be distressing for parents, who often feel vulnerable and incompetent in the high-tech NICU environment [17][18][19] . Parents may present with difficulties in understanding and capturing subtle cues from their infant 20 .
Although the hospitalization of a preterm neonate may affect both parents equally 30 , most of the studies examining parental emotional distress focused on mothers' experience and needs 18 31 32 . After birth, the mother normally initiates specific behaviours towards her newborn, which aim at supporting the neonate who experiences high levels of stress during hospitalization in the NICU 33 , and foster the infant's socioemotional development 34 35 . However, mothers of preterm infants may present difficulties in  36 . Thus, parental stress may interfere with the infant's socioemotional and cognitive development, and is associated with more difficulties in building positive parent-infant relationships due to disrupted interactions 34 37 38 .
However, a recent meta-analysis showed that mothers of preterm children were not less sensitive or responsive toward their children than mothers of full-term children 39 .

Parenting self-efficacy
Parenting self-efficacy is defined as 'beliefs or judgements a parent holds of their capabilities to organize and execute a set of tasks related to parenting a child' 40 . Selfefficacy includes two separate notions; first, the belief of competence in caring for one's own child and successful incarnation of the parental role (general self-efficacy) 41 , and secondly, the skills required for parenting (specific self-efficacy) 42 . The present study will focus on the specific self-efficacy, which drives actions and predicts parents' performances and behaviours 43 44 .
As demonstrated in previous studies, parenting self-efficacy appears to mediate the relationship between psychosocial risk factors and maternal competences 45 46 . Thus, a perception of low self-efficacy is associated with parental depression 45 47-50 , high levels of parenting stress 51 52 , low family support 53 , poor infant health 52 54 , and demanding infant temperament 55 56 . In contrast, a perception of high self-efficacy is associated with sensitive and receptive parental behaviour, and is related to improved infant socioemotional development 49 57 .
Parents of preterm neonates face a complex challenge. While they might be responsive to their infant cues, preterm neonates might not be capable of engaging in sustained and responsive interaction, as they tend to be less attentive and reactive due to immaturity, and to show more negative behaviours and emotions, as well as less rewarding interactions than their term-born peers 49 [58][59][60] . In parallel, mothers of preterm neonates, who are at risk of experiencing depression, anxiety or post-traumatic disorder 19 29 , may not be able to interact as adequately with their child, and could be less sensitive than mothers without mental health symptoms. Mothers of preterm infants may be at a higher risk of decreased maternal confidence 61 , although the limited evidence available so far is mixed 50 62 . The quality of care provided by parents is strongly influenced by the maternal perception of self-efficacy, and interventions promoting this may therefore help to increase parenting quality 63 64 .
To date, only few early interventions have focused on enhancing perceived parenting self-efficacy. The interventions that are currently available in the early neonatal period mainly aim to decrease parental trauma and stress-related symptoms, and to improve parental responsiveness within the parent-infant interaction 17 [65][66][67] . Thus, a recent meta-analysis identified only two interventions intended to increase maternal self-efficacy [68][69][70] . These two interventions concentrated on different techniques of parenting education, and one of the two demonstrated improved cognitive child development at 4 months of age 70 . The present study focuses on the joint observation, which is an interdisciplinary intervention performed in the NICU soon after birth with distinct objectives. Among them, increasing perceived parenting self-efficacy may represent a good indicator of the effects of this early intervention.

Joint observation
The joint observation (JOIN: Joint Observation In Neonatology 71   This intervention is based on four distinct theories describing neonatal and infant development. First, the evaluation of neonatal behaviour developed by Brazelton and Nugent 72 underlines the importance of parents detecting the neonate's competences and fragilities, and interpreting stress cues to adjust to the infant's regulation needs. Second, the synactive model of Als 73 proposes a program of individualized care avoiding overstimulation in the NICU and supporting the neonate's self-regulation and competences. Third, the sensorimotor approach elaborated by Bullinger 74 consists mainly of the assessment of sensory dystimulations provided to the neonate, and the management of subsequent tonico-postural disturbances observed during the NICU stay with the long-term perspective of optimizing his development. This approach builds a framework to adjust the care procedures to the neonate's capacity to treat multisensory information, and to reach a sensoritonic balance that allows and supports interactive behaviours. Fourth, the interactive guidance is a model based on the observation and analysis of parent-infant interactions trough the therapeutic use of video-feedback [75][76][77] . This approach aims to allow parents to become aware of their competences and resources, as well as the skills and needs of their infant. Video-feedback has recently been studied as an intervention in the NICU 78 79 . The authors postulated that the interactive guidance through video-feedback reduces the negative impact of preterm birth on the parent-infant relationship, and the behavioural withdrawal of the parent. Results revealed increased parental sensitivity and positive effects on the developing relationship 78   The joint observation pragmatically consists of two phases. Firstly, a video-recorded period of routine care for the preterm neonate (such as a nappy change) is carried out by both the parent (mostly the mother) and a NICU nurse. Secondly, several short extracts of the period of care are carefully selected by the observers in order to reach the main objective of the intervention that can be summarized as follows: increasing the parents' confidence in caring for their own infant, as well as in their own capacity to build the parentinfant relationship, and to support their infant's development. With this main goal in mind, observers will play back the extracts to the parents, showing short specific moments of interactive behaviours that usually escape awareness. This video-feedback is conducted in order to point out the quality of the relational and emotional parent-infant interactions, and highlights moments of attunement, adjustment, synchrony, reciprocity and mutuality.

Aims of the present study
The objectives of the present study are to measure the effects of the joint observation as an early intervention performed in the NICU on outcomes relative to parental perception and mental health, as well as to indices of the parent-infant relationship quality and of child development. The primary outcome measure will be the perceived maternal self-efficacy. Secondary objectives will be to measure the impact of this intervention on maternal mental health (including perceived stress, posttraumatic stress, anxiety, depression), on maternal perception of the parent-infant relationship, on maternal responsiveness, and on the neurodevelopment of the infant at 6 months corrected age (CA).
In addition, acceptability of the intervention and maternal satisfaction will be assessed.

Study Design
We will conduct a monocentric randomized controlled trial testing an intervention compared with treatment-as-usual, in the level III NICU of a Swiss University Hospital.

Study population, recruitment, group allocation, and blinding
All mothers of preterm neonates born between 28 and 32 6/7 weeks of gestational age (GA), admitted to the NICU, and aged less than 8 weeks of life are eligible to participate.
Exclusion criteria include the following: maternal age <18 years, established intellectual disability or psychotic illness, insufficient French-speaking level to fulfil questionnaires, and cardio-respiratory instability of the preterm neonate (severe brady-apnea syndrome, oxygen requirement >30%). Regarding twins or triplets, only the first-born neonate or the one being more stable will be included in the study.
Recruitment will be performed by the study nurses, who approach the eligible mothers once their infants are stable enough. The allocation ratio of randomisation is 1:1, using a computer-generated list of random blocks (https://www.sealedenvelope.com/simple-randomiser). The allocation sequence will be concealed from the principal investigator in sequentially numbered, opaque, sealed envelopes. Envelopes will be opened only after the enrolled participants gave signed consent and completed all baseline assessments. The principal investigator and the statistician will be blind to group allocation. All participant data will be coded to ensure confidentiality.

Control group
Participants in the control group will receive treatment-as-usual. They will be asked to complete questionnaires at the same time-points as the participants in the intervention group: at recruitment, at one month after enrolment, and at 6 months of their infant's corrected age (CA). At 6 months CA, a neurodevelopmental assessment of the infant and a 10-min filmed mother-infant interaction will take place.

Intervention group
Mothers assigned to the intervention group will be asked to complete self-report questionnaires at the three time-points described above. The intervention in the form of the joint observation will be planned after enrolment depending on the infant's clinical state and stability. The intervention is two-fold: firstly, two professionals (a study nurse, a child psychologist or psychiatrist) are jointly observing a period of care administered to the neonate jointly by her mother and a NICU nurse. The care procedure is video-taped and an observation grid 81 is completed by the observer. Secondly, the mother and the NICU nurse participate in a video-feedback session with the two observers. The discussion is based on the principles of interactive guidance 78 , as described above. At the end of the intervention, the mother will also be asked to complete a questionnaire regarding her satisfaction with the intervention. At 6 months CA, a neurodevelopmental assessment of the infant and a 10-min filmed mother-infant interaction will be carried out. The primary outcome is the difference in perceived maternal self-efficacy between the control and intervention groups measured with the Perceived Maternal Parenting Self-Efficacy (PMP-SE) questionnaire one month after study enrolment.

Maternal outcomes
Using validated self-reported questionnaires described below, various aspects of maternal well-being will be compared between the two groups at baseline and at the 1-month and 6-month follow-up, including symptoms of PTSD Study Social Support Survey), and maternal sensitivity or responsiveness (Emotional Availability Scales and Care Index). In addition, acceptability and maternal satisfaction of the intervention will be assessed in the intervention group.

Neonatal outcomes
The neurodevelopmental outcome of the preterm neonates will be measured  F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y   16 After enrolment, mothers will be asked to complete several questionnaires described below, and again one month after study enrolment, and at 6 months CA. Infants will return at 6 months CA to the neonatal follow-up clinic for the neurodevelopmental assessment and the 15-min filmed mother-infant interaction. The study measures and timings are summarized in Table 1 and Figure 1.

Perceived Maternal Parenting Self-Efficacy (PMP-SE)
This questionnaire including 20 items, which represent 4 subscales (care taking procedures, evoking behaviour(s), reading behaviours or signalling, and situational beliefs), was specifically developed for mothers of preterm neonates, and has good psychometric properties 42 . Responses to each item are recorded on a fourpoint Likert scale (from 'strongly disagree' -score 1 to 'strongly agree' -score 4). To obtain a French version of the questionnaire, a translation and cultural adaptation was performed with the forward-backward method 82 .

Posttraumatic Diagnosis Scale (PDS-F)
Maternal PTSD is measured using this 17-items scale based on DSM-IV criteria. Mothers will rate frequency and severity of symptoms, such as reexperiencing, avoidance and hyperarousal, experienced over the last month, and graded on a four-point Likert scale. The PDS displays good psychometric properties 83 , and a French version has been validated 84 . The questionnaire assessed parental stress with 31 items focusing on their perception of stress factors during the NICU stay of their neonate and explores three domains: impact of the visual and auditory environment, behaviour and aspect of the neonate, and parental role 85 .

Parenting Stress Index-Short form (PSI-SF)
This 36-items questionnaire is a shortened version of the Parental Stress Index 86 , which measures the stress related to parenthood, and is intended for parents of children 0 to 3 years. The three subscales investigate parental distress, dysfunctional interactions between the parents and the child, and child difficulties.
Its validity has been demonstrated in studies of parents of preterm neonates 87 . In this study, the validated French version will be used 88 .

Hospital Anxiety and Depression Scale (HADS)
Anxiety and depression symptoms are assessed using the French version of the HADS, which includes 14 items, and measures the severity of symptoms 89 . This questionnaire has good psychometric properties 90 .

Edinburgh Postnatal Depression Scale (EPDS)
Maternal depression symptoms will also be assessed with the EPDS, which focuses on the symptoms experienced over the last 7 days 91

Mother-to-Infant Bonding Scale (MIBS)
In this questionnaire, the mother rates (from 0 to 5) eight adjectives describing her feelings toward her infant, which is indicative of mother-infant bonding 93 94 and was translated into French 95 .

Infant Behaviour Questionnaire -Revised (IBQ-R) Very Short Form
Infant temperament is assessed through the French version of this questionnaire (total of 191 items). The parent reports on a 7-points Likert scale the frequency of his infant's behaviours during the previous two weeks 96 .

Modified Medical Outcomes Study Social Support Survey (mMOS-SS)
This validated self-reported evaluation consisting of eight items measuring different aspects of social support 97 is based on the 19-items questionnaire assessing the dimensionality of four functional support scales (emotional/informative, tangible, affectionate, and positive social interaction) 98 . A French translation and cultural adaptation was performed using the forward-back method 82 .

Questionnaire of satisfaction and acceptability of the intervention
This questionnaire comprises a general question on maternal satisfaction with the intervention and six questions on its setting, value and usefulness, which will provide a qualitative evaluation. In addition, three questions focus on the acceptability of the intervention by the mothers.

Demographic and perinatal characteristics
Mothers will also report demographic information, including socio-economic status, level of education 99 , and previous psychiatric disease. Neonatal characteristics will be collected from the medical record on severity of morbidity (GA and weight at birth, Apgar score, complications -need for mechanical ventilation and respiratory morbidity, sepsis, and cerebral lesions), as well as the Clinical Risk Index for Babies (CRIB) 100 , which represents neonatal morbidity severity.

Assessment of maternal sensitivity and responsiveness
Maternal sensitivity will be assessed at 6 months CA by coding a session of free play between the mother and her infant with the Emotional Availability Scales (EAS) 101 . Six domains are evaluated, of which four relate to the mother's behaviour (sensitivity, structuration, intrusion and hostility toward the infant), and two to the infant's behaviour (reactivity to the mother and maternal involvement). Patterns of interaction and emotional availability can therefore be measured on separate scales 102 .
A second tool, the Care Index 103 , will measure maternal sensitivity, by assessing the interactive behaviour within the mother-infant dyad according to seven scales (facial expressions, vocalizations, posture, expressed affection, turn-taking, control and activity).
Three maternal (sensitive, controlling, passive) and four infant (cooperative, compulsivecompliant, demanding, passive) characteristic behaviours are coded on each scale.

Neurodevelopmental assessment of the infant
A standardized neurodevelopmental assessment will be conducted at 6 104 , which entails three subscales (cognitive, language and motor) with a normative mean score of 100 ± 15 SD.

Sample size calculation
Power calculation (G*Power) 105 based on published means and standards deviations 42 48 related to perceived parental self-efficacy in a sample of preterm (M = 58.51, SD = 12.57) and of term-born (M = 65.9, SD = 8.2) neonates showed that 68 participants would need to be recruited (α = 0.05, 1-β = 0.80, unilateral hypothesis). This is based on the assumption that parental self-efficacy in mothers of preterm babies in the intervention group who benefitted from the intervention would be comparable to that in mothers of term babies. Therefore, it is planned that 80 mothers will be enrolled to anticipate possible participant withdrawal.

STATISTICAL ANALYSES
For the primary outcome regarding the difference in the perceived maternal selfefficacy between the intervention and control groups, linear regression analysis will be employed. For the secondary aims, the analyses will be performed both for differences in changes between the intervention and the control group and for differences between groups at different time points using linear regression analysis. Associations between outcomes will be tested using linear regression analyses.
Differences between groups will be adjusted for the respective baseline values in case they differ. Variables will be transformed if residuals are not normally distributed. We will include potential confounding variables, if necessary. These include maternal age, sex of Bonferroni correction for multiple analyses will be applied. For initial exploratory analyses, no such correction will be used 106 .

ADVERSE EVENTS
Expected and unexpected adverse events will be recorded during the study period.
As the intervention does not involve medical or pharmaceutical treatment, the risk that an adverse event would occur is low. A child psychiatrist will be available for clinical assessment and follow-up if needed, particularly if significant psychological distress or psychiatric illness is detected during study participation.

DATA MANAGEMENT
All study data will be coded and entered by research staff (psychology assistant). The database will be regularly updated by the IT Service of the Lausanne University Hospital.
Double data entry will be done for the primary outcomes. For the rest of the data, a random 5% will be double-checked. The principal investigator, the co-investigators and the statistician will have access to the final trial dataset. Individual participant data collected during the trial (after deidentification) on which publications from JOIN consortium are based will be available on reasonable request. obtained from all participating mothers. Participation in the study will not interfere with the typical care patients receive after childbirth and during NICU stay. Results from the study will be disseminated at national and international conferences, and in peer-reviewed journals. This randomized controlled trial is registered in clinicaltrials.gov (NCT02726136).

SIGNIFICANCE AND OUTLOOK
This study might result in an evidence-based early intervention aiming to reinforce parental competences, in particular to increase perceived parental self-efficacy. It would represent a brief, easily accessible, and safe early intervention, which could be implemented in the routine care in the NICU, thus leading to significant changes in clinical practice. It will also help to characterize the relationships between perceived parental self-efficacy, maternal mental health, maternal perception of their relationship with their infant and their infant's temperament, and maternal sensitivity.
Due to its interdisciplinary nature, this research is of interest for clinicians, educators and researchers in the field of paediatrics and development, psychology, psychiatry, and public health.

Maternal perception of her infant's temperament
Maternal sensitivity x

Maternal satisfaction
Satisfaction questionnaire  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58   Roles and responsibilities 5a Names, affiliations, and roles of protocol contributors 23 5b Name and contact information for the trial sponsor n/a 5c Role of study sponsor and funders, if any, in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities n/a 5d Composition, roles, and responsibilities of the coordinating centre, steering committee, endpoint adjudication committee, data management team, and other individuals or groups overseeing the trial, if applicable (see Item 21a for data monitoring committee) n/a Trial design 8 Description of trial design including type of trial (eg, parallel group, crossover, factorial, single group), allocation ratio, and framework (eg, superiority, equivalence, noninferiority, exploratory) 13

Methods: Participants, interventions, and outcomes
Study setting 9 Description of study settings (eg, community clinic, academic hospital) and list of countries where data will be collected. Reference to where list of study sites can be obtained 13 Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and individuals who will perform the interventions (eg, surgeons, psychotherapists)

13
Interventions 11a Interventions for each group with sufficient detail to allow replication, including how and when they will be administered 9-11, 14, Table 1, Figure 1 11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, or improving/worsening disease) n/a 11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (eg, drug tablet return, laboratory tests) n/a 11d Relevant concomitant care and interventions that are permitted or prohibited during the trial 13 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended

14-15
Participant timeline 13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for participants. A schematic diagram is highly recommended (see Figure) 15-16, Table 1, Figure 1 Page 37 of 40

Methods: Assignment of interventions (for controlled trials)
Allocation: Sequence generation 16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions 13 Allocation concealment mechanism 16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned 13 Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to interventions 13 Blinding (masking) 17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, data analysts), and how 13 17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant's allocated intervention during the trial n/a

Data collection methods 18a
Plans for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known. Reference to where data collection forms can be found, if not in the protocol 15-20 18b Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols n/a Methods for any additional analyses (eg, subgroup and adjusted analyses) 21 20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any statistical methods to handle missing data (eg, multiple imputation) 21

Methods: Monitoring
Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed n/a 21b Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial n/a

Harms 22
Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse events and other unintended effects of trial interventions or trial conduct 21 Auditing 23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent from investigators and the sponsor n/a How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial 13, 21

Ethics and dissemination
Declaration of interests 28 Financial and other competing interests for principal investigators for the overall trial and each study site 23 Access to data 29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators  Perceived parental self-efficacy represents the belief of efficacy in caring for one's own infant and successful incarnation of the parental role, as well as the perception of one's own abilities to complete a specified task. Interventions to support parental role, as well as infant development, are needed, and parental self-efficacy represents a useful indicator to measure the effects of such early interventions.

Methods and analysis
This study protocol describes a randomized controlled trial that will test an early intervention in the NICU (JOIN: Joint Observation In Neonatology) carried out by an interdisciplinary staff team. Mothers of preterm neonates born between 28 and The primary outcome will be the difference in the perceived maternal selfefficacy between the intervention and control groups assessed by self-report questionnaires. Secondary outcomes will be maternal mental health, the perception of the parent-infant relationship, maternal responsiveness, and the neurodevelopment of the infant at 6 months corrected age.

Ethics and dissemination
Ethical approval was granted by the Human Research Ethics Committee of the Canton de Vaud (study number 496/12). Results from this study will be disseminated at national and international conferences, and in peer-reviewed journals.  Among other objectives, the intervention aims at increasing perceived parental selfefficacy in mothers of very preterm infants.
 The intervention draws on theories of neonatal and infant development, as well as interactive video guidance.
 Methodological rigour, including concealment of random allocation and prospective trial registration and publication, limits risk of bias.
 Unblinded participants and clinicians may increase the risk of bias.

Advances in Neonatal Care
Improvement of pre-and postnatal care over the past decades has led to increased survival of very preterm neonates born less than 32 weeks' gestation 1 .
Among others, protective measures to promote health and subsequent neurodevelopment have been developed, including optimization of nutritional support, better characterization of neonatal stress, and improved pain management.
In the same perspective, developmental care was introduced in the Neonatal Intensive Care Units (NICU) since the 90's with the intention of minimizing the adverse consequences of prematurity on the developing brain. During a critical period of development, the preterm brain is highly vulnerable to injury, represented by cerebral haemorrhage and insult to the white matter. Additionally, beyond the injury, preterm neonates are prone to alteration of brain maturation with disruption of normal developmental trajectory of both grey and white matters 2-4 . focuses on the child's well-being through the adaptation of the sensorial environment in order to provide more physiological external stimuli (tactile, auditory, visual, vestibular), that will help to promote behaviors and postures fostering comfort and regulation. The third objective of the developmental care aims to support parents in their role and to strengthen the relationship they are developing with their child 7 9 10 .

Impact of prematurity on parents' well-being
Preterm birth and caring for a preterm infant may be distressing for parents, who often feel vulnerable and incompetent in the high-tech NICU environment [20][21][22] .
Parents may present with difficulties in understanding and capturing subtle cues from their infant 23 . Parents show important signs of stress 24 , and require more support during the first year after the preterm birth compared with parents of term infants 25 .
Although the hospitalization of a preterm neonate may affect both parents equally 33 , most of the studies examining parental emotional distress so far focused on mothers' experience and needs 21 34 35 . After birth, the mother normally initiates specific behaviors towards her newborn, aimed at supporting the neonate who experiences high levels of stress during hospitalization in the NICU 36 , and at fostering the infant's socioemotional development 37 38 . However, mothers of preterm infants may present difficulties in developing these protective behaviours 39 . Thus, parental stress may interfere with the infant's socioemotional and cognitive development, and is associated with more difficulties in building positive parentinfant relationships due to disrupted interactions 37 40 41 . However, a recent metaanalysis showed that mothers of preterm children were not less sensitive or responsive toward their children than mothers of full-term children 42 .

Perceived parental self-efficacy
Perceived parental self-efficacy is defined as 'beliefs or judgements a parent holds of their capabilities to organize and execute a set of tasks related to parenting a child' 43 . Self-efficacy includes two separate notions; first, the belief of efficacy in caring for one's own child across several varied domains of functioning and successful incarnation of the parental role (general self-efficacy) [44][45][46] , and secondly, the perception of one's own abilities to complete a specified task within a specific domain (specific self-efficacy) 47 . The present study will focus on the specific selfefficacy, which appears to drive actions and predicts parents' behaviors 45 48 . As demonstrated in previous studies, perceived parental self-efficacy appears to mediate the relationship between psychosocial risk factors and maternal competences 49 50 . Thus, a perception of low self-efficacy is associated with parental depression 49 51-54 , high levels of parenting stress 55 56 , low family support 57 , poor infant health 56 58 , and demanding infant temperament 59 60 . In contrast, a perception of high self-efficacy is associated with sensitive and receptive parental behavior, and is related to improved infant socioemotional development 53 61 .
Parents of preterm neonates face a complex challenge. While they might be responsive to their infant cues, preterm neonates might not be capable of engaging in sustained and responsive interaction, as they tend to be less attentive and reactive due to immaturity, and to show more negative behaviors and emotions, as well as less rewarding interactions than their term-born peers 53 62-64 . In parallel, mothers of preterm neonates, who are at risk of experiencing depression, anxiety or post-traumatic disorder 22 32 , may not be able to interact as adequately with their child, and could be less sensitive than mothers without mental health symptoms.
Mothers of preterm infants may be at a higher risk of decreased maternal confidence 65 , although the limited evidence available so far is mixed 54 66 . The quality of care  73 . The present study focuses on the joint observation, which is an interdisciplinary intervention performed in the NICU soon after birth. The main aim of the study is to examine whether this early intervention increases perceived parental self-efficacy.   There is no intervention by the observers during the videotaping. Secondly, before gathering with the mother, several short extracts of the period of care are carefully selected by the observers in order to reach the objectives of the intervention. During the discussion and for illustration purpose, the observers will play back 4-6 short extracts of 10-30 seconds each to the parents, showing short specific moments of interactive behaviors that usually escape awareness. This video-feedback, which lasts about 60 minutes, is conducted in order to point out the quality of the relational and emotional parent-infant interactions, and highlights moments of attunement, adjustment, synchrony, reciprocity, and mutuality. The objectives of the present study are to measure the effects of the joint observation as an early intervention performed in the NICU on outcomes relative to parental perception and mental health, as well as to indices of the parent-infant relationship quality and of child development. The primary outcome measure will be the perceived maternal self-efficacy. Secondary objectives will be to measure the impact of this intervention on maternal mental health (including perceived stress, post-traumatic stress, anxiety, depression), on maternal perception of the parentinfant relationship, on maternal responsiveness, and on the neurodevelopment of the infant at 6 months corrected age (CA). In addition, acceptability of the intervention and maternal satisfaction will be assessed.

Study Design
We will conduct a monocentric randomized controlled trial testing an intervention compared with treatment-as-usual, in the level III NICU of a Swiss University Hospital.

Study population, recruitment, group allocation, and blinding
All mothers of preterm neonates born between 28 and 32 6/7 weeks of gestational age (GA), admitted to the NICU, and aged less than 8 weeks of life are eligible to participate. Exclusion criteria were set for ethical considerations and in order to avoid approaching mothers needing acute treatment, and include the following: maternal age <18 years; established intellectual disability or psychotic illness; insufficient French-speaking level to complete questionnaires due to impossibility to obtain valid translations to multiples languages for financial reasons; and cardio-respiratory instability of the preterm neonate (severe brady-apnea Regarding twins or triplets, only the first-born neonate or the one being more stable will be included in the study.
Recruitment will be performed by the study nurses, who approach the eligible mothers once their infants are stable enough, i.e., after the critical period of the first week of life when cardio-respiratory stability is established, usually on non-invasive ventilation and with oxygen requirement <30%, which would also permit more active participation of the parents in the neonate's care. The allocation ratio of randomisation is 1:1, using a computer-generated list of random blocks (https://www.sealedenvelope.com/simple-randomiser). The allocation sequence will be concealed from the principal investigator in sequentially numbered, opaque, sealed envelopes. Envelopes will be opened only after the enrolled participants gave signed consent and completed all baseline assessments. The principal investigator and the statistician will be blind to group allocation. All participant data will be coded to ensure confidentiality. Participants in the control group will receive treatment-as-usual. They will be asked to complete questionnaires at the same time-points as the participants in the intervention group: at recruitment, at one month after enrolment, and at 6 months of their infant's corrected age (CA). At 6 months CA, a neurodevelopmental assessment of the infant and a 10-min filmed mother-infant interaction will take place.

Intervention group
Mothers assigned to the intervention group will be asked to complete selfreport questionnaires at the three time-points described above. The intervention in the form of the joint observation will be planned after enrolment depending on the infant's clinical state and stability. The intervention is two-fold: firstly, the observers are jointly observing a period of care administered to the neonate jointly by her mother and a NICU nurse. The care procedure is video-taped and an observation grid 84 is completed by the observers. Secondly, the mother and the NICU nurse participate in a video-feedback session with the two observers. The discussion is based on the principles of interactive guidance 81 , as described above. At the end of  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y 23 the intervention, the mother will also be asked to complete a questionnaire regarding her satisfaction with the intervention.
At 6 months CA, a neurodevelopmental assessment of the infant and a 10min filmed mother-infant interaction will be carried out.

Primary outcome
The primary outcome is the difference in perceived maternal self-efficacy between the control and intervention groups measured with the Perceived Maternal Parenting Self-Efficacy (PMP-SE) questionnaire one month after study enrolment.

Maternal outcomes
Using validated self-reported questionnaires described below, various aspects of maternal well-being will be compared between the two groups at  Care Index). In addition, acceptability and maternal satisfaction of the intervention will be assessed in the intervention group.

Neonatal outcomes
The neurodevelopmental outcome of the preterm neonates will be

Data collection and visits
After enrolment, mothers will be asked to complete several questionnaires described below, and again one month after study enrolment, and at 6 months CA. Infants will return at 6 months CA to the neonatal follow-up clinic for the neurodevelopmental assessment and the 10-min filmed mother-infant interaction.
The study measures and timings are summarized in Table 1 and Figure 1.

Perceived Maternal Parenting Self-Efficacy (PMP-SE)
This questionnaire including 20 items, which represent 4 subscales (care taking procedures, evoking behaviour(s), reading behaviours or signalling, and situational beliefs), was specifically developed for mothers of preterm neonates, and has good psychometric properties 47 . Responses to each item are recorded on a four-point Likert scale (from 'strongly disagree'score 1 to 'strongly agree' -score 4). To obtain a French version of the questionnaire, a translation and cultural adaptation was performed with the forward-backward method 85 .  90 . In this study, the validated French version will be used 91 .

Hospital Anxiety and Depression Scale (HADS)
Anxiety and depression symptoms are assessed using the French version of the HADS, which includes 14 items, and measures the severity of symptoms 92 . This questionnaire has good psychometric properties 93 .

Edinburgh Postnatal Depression Scale (EPDS)
Maternal depression symptoms will also be assessed with the EPDS, which focuses on the symptoms experienced over the last 7 days 94 . The French version displays good psychometric characteristics 95 . In this questionnaire, the mother rates (from 0 to 5) eight adjectives describing her feelings toward her infant, which is indicative of mother-infant bonding 96 97 and was translated into French with good psychometric properties 98 .

Infant Behaviour Questionnaire -Revised (IBQ-R) Very Short Form
Infant temperament is assessed through the French version of this questionnaire (total of 191 items). The parent reports on a 7-points Likert scale the frequency of his infant's behaviours during the previous two weeks 99 . Good psychometric properties haven reported 99 .

Modified Medical Outcomes Study Social Support Survey (mMOS-SS)
This validated self-reported evaluation consisting of eight items measuring different aspects of social support 100 is based on the 19-items questionnaire assessing the dimensionality of four functional support scales (emotional/informative, tangible, affectionate, and positive social interaction)  101 . A French translation and cultural adaptation was performed using the forward-back method 85 .

Questionnaire of satisfaction and acceptability of the intervention
This questionnaire comprises a general question on maternal satisfaction with the intervention and six questions on its setting, value and usefulness, which will provide a qualitative evaluation. In addition, three questions focus on the acceptability of the intervention by the mothers.

Demographic and perinatal characteristics
Mothers will also report demographic information, including socio-economic status, level of education 102 , and previous psychiatric disorder. Neonatal characteristics will be collected from the medical record on severity of morbidity (GA and weight at birth, Apgar score, complications -need for mechanical ventilation and respiratory morbidity, sepsis, and cerebral lesions), as well as the Clinical Risk Index for Babies (CRIB) 103 , which represents neonatal morbidity severity.

Assessment of maternal sensitivity and responsiveness
Maternal sensitivity will be assessed at 6 months CA by coding a session of free play between the mother and her infant with the Emotional Availability Scales (EAS) 104 . Six domains are evaluated, of which four relate to the mother's behaviour (sensitivity, structuration, intrusion, and hostility toward the infant), and two to the infant's behaviour (reactivity to the mother and maternal involvement). Patterns of interaction and emotional availability can therefore be measured on separate scales 105 .
A second tool, the Care Index 106 , will measure maternal sensitivity, by assessing the interactive behaviour within the mother-infant dyad according to seven scales (facial expressions, vocalizations, posture, expressed affection, turn-taking, control and activity). Three maternal (sensitive, controlling, passive) and four infant (cooperative, compulsive-compliant, demanding, passive) characteristic behaviors are coded on each scale.  107 , which entails three subscales (cognitive, language and motor) with a normative mean score of 100 ± 15 SD.

Sample size calculation
Power calculation (G*Power) 108  This is based on the assumption that parental self-efficacy in mothers of preterm babies in the intervention group who benefitted from the intervention would be comparable to that in mothers of term babies. Therefore, it is planned that 80 mothers will be enrolled to anticipate possible participant withdrawal. For the primary outcome regarding the difference in the perceived maternal self-efficacy between the intervention and control groups, linear regression analysis will be employed, with maternal self-efficacy at 1 month as the dependent variable and group as the explanatory variable, with adjustment for baseline maternal selfefficacy. For secondary analyses, linear mixed model regressions will be conducted, with maternal self-efficacy at 1 and 6 months as dependent variables and group, time, and the interaction group x time as independent variables, adjusted for baseline maternal self-efficacy. The sample principle will be applied to all other secondary outcomes. We will include potential confounding variables, if necessary.

STATISTICAL ANALYSES
These include maternal age, sex of the children, and socioeconomic status where applicable. For confirmatory analyses, a Bonferroni correction for multiple analyses will be applied. For initial exploratory analyses, no such correction will be used 109 .
Differences between groups will be adjusted for the respective baseline values in case they differ using potential confounding variables, if necessary. These include maternal age, sex of children, and socioeconomic status where applicable.
Variables will be transformed if residuals are not normally distributed.

ADVERSE EVENTS
Expected and unexpected adverse events will be recorded during the study period. As the intervention does not involve medical or pharmaceutical treatment, the risk that an adverse event would occur is low. A child psychiatrist will be available for clinical assessment and follow-up if needed, particularly if significant psychological distress or psychiatric illness of the mother or her infant is detected during study participation.

DATA MANAGEMENT
All study data will be coded and entered by research staff (psychology assistant). The database will be regularly updated by the IT Service of the Lausanne University Hospital. Double data entry will be done for the primary outcomes. For the rest of the data, a random 5% will be double-checked. The principal investigator, the co-investigators and the statistician will have access to the final trial dataset.
Individual participant data collected during the trial (after deidentification) on which publications from JOIN consortium are based will be available on reasonable request.

SIGNIFICANCE AND OUTLOOK
This study might result in an evidence-based early intervention aimed at reinforcing parental competences, in particular at increasing perceived parental selfefficacy. It would represent a brief, easily accessible, and safe early intervention, which could be implemented in the routine care in the NICU, thus leading to Due to its interdisciplinary nature, this research is of interest for clinicians, educators and researchers in the field of paediatrics and development, psychology, child psychiatry, and public health.

PATIENTS AND PUBLIC INVOLVEMENT
In the early 2000's, the joint observation was introduced in our NICU by two professionals as part of the care of the parent-infant dyads 74 . Due to positive feedback from the parents, the intervention was more routinely performed and systematized to the point that a randomized controlled trial was needed to examine its validity.
Although patients and caregivers' feedback was considered in designing and adapting the intervention, they were not directly involved in the design or recruitment   Interventions for each group with sufficient detail to allow replication, including how and when they will be administered 9-11, 14, Table 1, Figure 1 11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, or improving/worsening disease) n/a 11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (eg, drug tablet return, laboratory tests) n/a 11d Relevant concomitant care and interventions that are permitted or prohibited during the trial 13 Outcomes 12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended

14-15
Participant timeline 13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for participants. A schematic diagram is highly recommended (see Figure) 15-16, Table 1, Figure 1 Page 53 of 56

Methods: Assignment of interventions (for controlled trials)
Allocation: Sequence generation 16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions 13 Allocation concealment mechanism 16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned 13 Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to interventions 13 Blinding (masking) 17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, data analysts), and how 13 17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant's allocated intervention during the trial n/a

Data collection methods 18a
Plans for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known. Reference to where data collection forms can be found, if not in the protocol 15-20 18b Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols n/a Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any statistical methods to handle missing data (eg, multiple imputation) 21

Methods: Monitoring
Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed n/a 21b Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial n/a How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial 13, 21 Declaration of interests 28 Financial and other competing interests for principal investigators for the overall trial and each study site 23 Access to data 29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators   e  w  o  n  l  y  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59 1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59 1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  Perceived parental self-efficacy represents the belief of efficacy in caring for one's own infant and successful incarnation of the parental role, as well as the perception of one's own abilities to complete a specified task. Interventions to support parental role, as well as infant development, are needed, and parental self-efficacy represents a useful indicator to measure the effects of such early interventions.

Methods and analysis
This study protocol describes a randomized controlled trial that will test an early intervention in the NICU (JOIN: Joint Observation In Neonatology) carried out by an interdisciplinary staff team. Mothers of preterm neonates born between 28 and  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60 F o r p e e r r e v i e w o n l y 5 32 6/7 weeks of gestational age are eligible for the study. The intervention consists of a videotaped observation by a clinical child psychologist or child psychiatrist and a study nurse of a period of care delivered to the neonate by the mother and a NICU nurse. The care procedure is followed by an interactive video guidance intended to demonstrate the neonate's abilities and resources to his parents.
The primary outcome will be the difference in the perceived maternal selfefficacy between the intervention and control groups assessed by self-report questionnaires. Secondary outcomes will be maternal mental health, the perception of the parent-infant relationship, maternal responsiveness, and the neurodevelopment of the infant at 6 months corrected age.

Strengths and limitations of this study
 The study will test the effects of an early intervention carried out by an interdisciplinary partnership between NICU nurses and clinical child psychologists/ child psychiatrists.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59   Unblinded participants and clinicians, as well as contamination due to improvement of usual care by health care providers, may increase the risk of bias.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  In the same perspective, developmental care was introduced in the Neonatal Intensive Care Units (NICU) since the 90's with the intention of minimizing the adverse consequences of prematurity on the developing brain. During a critical period of development, the preterm brain is highly vulnerable to injury, represented by cerebral haemorrhage and insult to the white matter. Additionally, beyond the injury, preterm neonates are prone to alteration of brain maturation with disruption of normal developmental trajectory of both grey and white matters 2-4 .  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y 10 Over the last two decades, a growing body of research focused on the impact of excessive stimuli such as sound, light, touch or pain on the preterm neonate, hypothesizing that an unfavourable and stressful environment may add to the adverse effects of neonatal morbidity 5 . These concerns led progressively to the introduction of developmental care, which consists of individualized strategies mainly based on the neonate's skills and/or difficulties 6 , and supporting the neonate's regulation and development. The first aim of the developmental care is to limit exposure to deleterious environmental stimulations. Management of sensorial dystimulation, as well as of pain and stress during invasive care procedures, represents a central target of developmental care 7 8 . The second main objective focuses on the child's well-being through the adaptation of the sensorial environment in order to provide more physiological external stimuli (tactile, auditory, visual, vestibular), that will help to promote behaviors and postures fostering comfort and regulation. The third objective of the developmental care aims to support parents in their role and to strengthen the relationship they are developing with their child 7 9 10 .

Impact of prematurity on parents' well-being
Preterm birth and caring for a preterm infant may be distressing for parents, who often feel vulnerable and incompetent in the high-tech NICU environment [23][24][25] .
Parents may present with difficulties in understanding and capturing subtle cues from their infant 26 . Parents show important signs of stress 27 , and require more support during the first year after the preterm birth compared with parents of term infants 28 .
Although the hospitalization of a preterm neonate may affect both parents equally 36 , most of the studies examining parental emotional distress so far focused on mothers' experience and needs 24 37 38 . After birth, the mother normally initiates specific behaviors towards her newborn, aimed at supporting the neonate who  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y 12 experiences high levels of stress during hospitalization in the NICU 39 , and at fostering the infant's socioemotional development 40 41 . However, mothers of preterm infants may present difficulties in developing these protective behaviours 42 . Thus, parental stress may interfere with the infant's socioemotional and cognitive development, and is associated with more difficulties in building positive parentinfant relationships due to disrupted interactions 40 43 44 . However, a recent metaanalysis showed that mothers of preterm children were not less sensitive or responsive toward their children than mothers of full-term children 45 .

Perceived parental self-efficacy
Perceived parental self-efficacy is defined as 'beliefs or judgements a parent holds of their capabilities to organize and execute a set of tasks related to parenting a child' 46 . Self-efficacy includes two separate notions; first, the belief of efficacy in caring for one's own child across several varied domains of functioning and successful incarnation of the parental role (general self-efficacy) [47][48][49] , and secondly, the perception of one's own abilities to complete a specified task within a specific  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y 13 domain (specific self-efficacy) 50 . The present study will focus on the specific selfefficacy, which appears to drive actions and predicts parents' behaviors 48 51 .
As demonstrated in previous studies, perceived parental self-efficacy appears to mediate the relationship between psychosocial risk factors and maternal competences 52 53 . Thus, a perception of low self-efficacy is associated with parental depression 52 54-57 , high levels of parenting stress 58 59 , low family support 60 , poor infant health 59 61 , and demanding infant temperament 62 63 . In contrast, a perception of high self-efficacy is associated with sensitive and receptive parental behavior, and is related to improved infant socioemotional development 56 64 .
Parents of preterm neonates face a complex challenge. While they might be responsive to their infant cues, preterm neonates might not be capable of engaging in sustained and responsive interaction, as they tend to be less attentive and reactive due to immaturity, and to show more negative behaviors and emotions, as well as less rewarding interactions than their term-born peers 56 65-67 . In parallel, mothers of preterm neonates, who are at risk of experiencing depression, anxiety or post-traumatic disorder 25 35 , may not be able to interact as adequately with their child, and could be less sensitive than mothers without mental health symptoms. Mothers of preterm infants may be at a higher risk of decreased maternal confidence 68 , although the limited evidence available so far is mixed 57 69 . The quality of care provided by parents is strongly influenced by the maternal perception of self-efficacy, and interventions promoting this may therefore help to increase parenting quality 49 70 .

Aims of the present study
The objectives of the present study are to measure the effects of the joint observation as an early intervention performed in the NICU on outcomes relative to parental perception and mental health, as well as to indices of the parent-infant relationship quality and of child development. The primary outcome measure will be the perceived maternal self-efficacy. Secondary objectives will be to measure the impact of this intervention on maternal mental health (including perceived stress, post-traumatic stress, anxiety, depression), on maternal perception of the parentinfant relationship, on maternal responsiveness, and on the neurodevelopment of the infant at 6 months corrected age (CA). In addition, acceptability of the intervention and maternal satisfaction will be assessed.

Study Design
We will conduct a monocentric randomized controlled trial testing an intervention compared with treatment-as-usual, in the level III NICU of a Swiss University Hospital.

Study population, recruitment, group allocation, and blinding
All mothers of preterm neonates born between 28 and 32 6/7 weeks of gestational age (GA), admitted to the NICU, and aged less than 8 weeks of life are eligible to participate. Exclusion criteria were set for ethical considerations and in order to avoid approaching mothers needing acute treatment, and include the following: maternal age <18 years; established intellectual disability or psychotic illness; insufficient French-speaking level to complete questionnaires due to impossibility to obtain valid translations to multiples languages for financial reasons; and cardio-respiratory instability of the preterm neonate (severe brady-apnea Regarding twins or triplets, only the first-born neonate or the one being more stable will be included in the study. Recruitment will be performed by the study nurses, who approach the eligible mothers once their infants are stable enough, i.e., after the critical period of the first week of life when cardio-respiratory stability is established, usually on non-invasive ventilation and with oxygen requirement <30%, which would also permit more active participation of the parents in the neonate's care. The allocation ratio of randomisation is 1:1, using a computer-generated list of random blocks (https://www.sealedenvelope.com/simple-randomiser). The allocation sequence will be concealed from the principal investigator in sequentially numbered, opaque, sealed envelopes. Envelopes will be opened only after the enrolled participants gave signed consent and completed all baseline assessments. The principal investigator and the statistician will be blind to group allocation. All participant data will be coded to ensure confidentiality. Participants in the control group will receive treatment-as-usual. They will be asked to complete questionnaires at the same time-points as the participants in the intervention group: at recruitment, at one month after enrolment, and at 6 months of their infant's corrected age (CA). At 6 months CA, a neurodevelopmental assessment of the infant and a 10-min filmed mother-infant interaction will take place.

Intervention group
Mothers assigned to the intervention group will be asked to complete selfreport questionnaires at the three time-points described above. The intervention in the form of the joint observation will be planned after enrolment depending on the infant's clinical state and stability. The intervention is two-fold: firstly, the observers are jointly observing a period of care administered to the neonate jointly by her mother and a NICU nurse. The care procedure is video-taped and an observation grid 87 is completed by the observers. Secondly, the mother and the NICU nurse participate in a video-feedback session with the two observers. The discussion is based on the principles of interactive guidance 84 , as described above. At the end of  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y 23 the intervention, the mother will also be asked to complete a questionnaire regarding her satisfaction with the intervention. At 6 months CA, a neurodevelopmental assessment of the infant and a 10min filmed mother-infant interaction will be carried out.

Primary outcome
The primary outcome is the difference in perceived maternal self-efficacy between the control and intervention groups measured with the Perceived Maternal Parenting Self-Efficacy (PMP-SE) questionnaire one month after study enrolment.

Neonatal outcomes
The neurodevelopmental outcome of the preterm neonates will be measured at 6 months CA (Bayley Scales of Infant Development, 3 rd Edition [BSID-III]).

Data collection and visits
After enrolment, mothers will be asked to complete several questionnaires described below, and again one month after study enrolment, and at 6 months CA. Infants will return at 6 months CA to the neonatal follow-up clinic for the neurodevelopmental assessment and the 10-min filmed mother-infant interaction.
The study measures and timings are summarized in Table 1 and Figure 1.

Hospital Anxiety and Depression Scale (HADS)
Anxiety and depression symptoms are assessed using the French version of the HADS, which includes 14 items, and measures the severity of symptoms 95 . This questionnaire has good psychometric properties 96 .

Infant Behaviour Questionnaire -Revised (IBQ-R) Very Short Form
Infant temperament is assessed through the French version of this questionnaire (total of 191 items). The parent reports on a 7-points Likert scale the frequency of his infant's behaviours during the previous two weeks 102 . Good psychometric properties haven reported 102 .

Questionnaire of satisfaction and acceptability of the intervention
This questionnaire comprises a general question on maternal satisfaction with the intervention and six questions on its setting, value and usefulness, which will provide a qualitative evaluation. In addition, three questions focus on the acceptability of the intervention by the mothers.

Assessment of maternal sensitivity and responsiveness
Maternal sensitivity will be assessed at 6 months CA by coding a session of free play between the mother and her infant with the Emotional Availability Scales (EAS) 107 . Six domains are evaluated, of which four relate to the mother's behaviour (sensitivity, structuration, intrusion, and hostility toward the infant), and two to the infant's behaviour (reactivity to the mother and maternal involvement). Patterns of interaction and emotional availability can therefore be measured on separate scales 108 .

Sample size calculation
Power calculation (G*Power) 111  This is based on the assumption that parental self-efficacy in mothers of preterm babies in the intervention group who benefitted from the intervention would be comparable to that in mothers of term babies. Therefore, it is planned that 80 mothers will be enrolled to anticipate possible participant withdrawal.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y   32 For the primary outcome regarding the difference in the perceived maternal self-efficacy between the intervention and control groups, linear regression analysis will be employed, with maternal self-efficacy at 1 month as the dependent variable and group as the explanatory variable, with adjustment for baseline maternal selfefficacy. For secondary analyses, linear mixed model regressions will be conducted, with maternal self-efficacy at 1 and 6 months as dependent variables and group, time, and the interaction group x time as independent variables, adjusted for baseline maternal self-efficacy. The sample principle will be applied to all other secondary outcomes. We will include potential confounding variables, if necessary.

STATISTICAL ANALYSES
These include maternal age, sex of the children, and socioeconomic status where applicable. For confirmatory analyses, a Bonferroni correction for multiple analyses will be applied. For initial exploratory analyses, no such correction will be used 112 .
Differences between groups will be adjusted for the respective baseline values in case they differ using potential confounding variables, if necessary. These include maternal age, sex of children, and socioeconomic status where applicable.

PATIENTS AND PUBLIC INVOLVEMENT
In the early 2000's, the joint observation was introduced in our NICU by two professionals as part of the care of the parent-infant dyads 77 . Due to positive feedback from the parents, the intervention was more routinely performed and systematized to the point that a randomized controlled trial was needed to examine its validity.
Although patients and caregivers' feedback was considered in designing and adapting the intervention, they were not directly involved in the design or recruitment of this study. However, results will be disseminated in written form to the participants and distributed to the public via social media and public events.

ADVERSE EVENTS
Expected and unexpected adverse events will be recorded during the study period. As the intervention does not involve medical or pharmaceutical treatment, the risk that an adverse event would occur is low. A child psychiatrist will be available for clinical assessment and follow-up if needed, particularly if significant psychological  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y 34 distress or psychiatric illness of the mother or her infant is detected during study participation.

DATA MANAGEMENT
All study data will be coded and entered by research staff (psychology assistant). The database will be regularly updated by the IT Service of the Lausanne University Hospital. Double data entry will be done for the primary outcomes. For the rest of the data, a random 5% will be double-checked. The principal investigator, the co-investigators and the statistician will have access to the final trial dataset.
Individual participant data collected during the trial (after deidentification) on which publications from JOIN consortium are based will be available on reasonable request.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47  48  49  50  51  52  53  54  55  56  57  58  59  60   F  o  r  p  e  e  r  r  e  v  i  e  w  o  n  l  y 35 informed consent will be obtained from all participating mothers. Participation in the study will not interfere with the typical care patients receive after childbirth and during NICU stay. Results from the study will be disseminated at national and international conferences, and in peer-reviewed journals. This randomized controlled trial is registered in clinicaltrials.gov (NCT02736136).

Methods: Participants, interventions, and outcomes
Study setting 9 Description of study settings (eg, community clinic, academic hospital) and list of countries where data will be collected. Reference to where list of study sites can be obtained 13 Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and individuals who will perform the interventions (eg, surgeons, psychotherapists)

13
Interventions 11a Interventions for each group with sufficient detail to allow replication, including how and when they will be administered 9-11, 14, Table 1, Figure 1 11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, or improving/worsening disease) n/a 11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (eg, drug tablet return, laboratory tests) n/a 11d Relevant concomitant care and interventions that are permitted or prohibited during the trial 13 Outcomes 12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended

14-15
Participant timeline 13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for participants. A schematic diagram is highly recommended (see Figure) 15-16, Table 1, Figure 1 Page 53 of 56

Methods: Assignment of interventions (for controlled trials)
Allocation: Sequence generation 16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions 13 Allocation concealment mechanism 16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned 13 Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to interventions 13 Blinding (masking) 17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, data analysts), and how 13 17b If blinded, circumstances under which unblinding is permissible, and procedure for revealing a participant's allocated intervention during the trial n/a

Methods: Data collection, management, and analysis
Data collection methods 18a Plans for assessment and collection of outcome, baseline, and other trial data, including any related processes to promote data quality (eg, duplicate measurements, training of assessors) and a description of study instruments (eg, questionnaires, laboratory tests) along with their reliability and validity, if known. Reference to where data collection forms can be found, if not in the protocol 15-20 18b Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols n/a Methods for any additional analyses (eg, subgroup and adjusted analyses) 21 20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any statistical methods to handle missing data (eg, multiple imputation) 21

Methods: Monitoring
Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed n/a 21b Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial n/a

Ethics and dissemination
26b Additional consent provisions for collection and use of participant data and biological specimens in ancillary studies, if applicable 13, 21

Confidentiality 27
How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial 13, 21 Declaration of interests 28 Financial and other competing interests for principal investigators for the overall trial and each study site 23 Access to data 29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators 21 Ancillary and posttrial care 30 Provisions, if any, for ancillary and post-trial care, and for compensation to those who suffer harm from trial participation n/a Dissemination policy 31a Plans for investigators and sponsor to communicate trial results to participants, healthcare professionals, the public, and other relevant groups (eg, via publication, reporting in results databases, or other data sharing arrangements), including any publication restrictions 21-22 31b Authorship eligibility guidelines and any intended use of professional writers n/a 31c Plans, if any, for granting public access to the full protocol, participant-level dataset, and statistical code 21

Appendices
Informed consent materials 32 Model consent form and other related documentation given to participants and authorised surrogates upon request Biological specimens 33 Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in the current trial and for future use in ancillary studies, if applicable n/a *It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation & Elaboration for important clarification on the items. Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons "Attribution-NonCommercial-NoDerivs 3.0 Unported" license.  1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26  27  28  29  30  31  32  33  34  35  36  37  38  39  40  41  42  43  44  45  46  47