Clinical trial NCT06379074: Poor Sleep During Pregnancy as Risk Factor for Post-partum Stress and Mental Health
Official title: Poor Sleep During Pregnancy as Risk Factor for Post-partum Stress and Mental Health: A Translational, Longitudinal and Clinical Study. Maternal Outcome After THERapy for Sleep (MOTHERS)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Postpartum Depression
Insomnia
Stress
Keywords: Insomnia
Pregnancy
Stress
Sleep health
Postpartum
Actigraphy
Cortisol
DNA methylation
CBT-I
Lead sponsor: University of Rome G. Marconi
Sponsor class: OTHER
Collaborators: name: University of Bologna
name: University of the Italian Switzerland
First posted: 2024-04-23
Enrollment: 114
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will receive a personal e-mail address to access their reserved area of the study's website. Each e-mail address is created using the pre-defined pseudonymized code, which will be assigned to each participant after screening (participants with sleep difficulties will be randomly assigned a code for condition B1 or B2).

This procedure is designed to increase privacy protection, allow for matching of responses throughout study's phases, and blind outcome assessors to participants allocation.

The personal website areas include contents based on their group allocation:

* A: online questionnaire and sleep diaries;
* B1: online questionnaire and sleep diaries; placebo intervention's contents (videos and pdf);
* B2: online questionnaire and sleep diaries; intervention's contents (videos and pdf); weekly optional private chat with a clinician (a psychotherapist expert in CBT-I and insomnia during pregnancy).
Primary purpose: TREATMENT

Brief summary: Improving maternal mental health is a worldwide health priority. Nevertheless, several scientific sources highlighted lack of empirical data which could drive clinical practice. The present project addresses psychobiological mechanisms leading to peripartum mental disorders. It focuses on one key risk factor for psychopathology, which is poor sleep continuity. The project aims to describe the link between maternal poor sleep quality and the cascade of events which may enhance vulnerability to stress and risk for mental disorders and to evaluate the efficacy of an online automated psychological prenatal intervention directed to sleep problems in preventing these negative outcomes.

Detailed description: The present trial aims to evaluate long-term effectiveness of a digital psychoeducational module based on CBT-I for expectant mothers complaining insomnia symptoms without psychiatric comorbidities on:

1. physiological, biological, genetical and subjective indices of maternal psychopathology, stress, and emotional processes. These outcomes will be assessed through online questionnaires and sleep diaries, cortisol levels, and recording of the sleep-wake activity through actigraphy;
2. father's and child's sleep and perceived stress. These outcomes will be assessed through online questionnaires and sleep diaries.

   114 expectant mothers will be evaluated from early pregnancy until 6 months post-partum.

   For power calculation of human studies, efficacy of clinical intervention for insomnia during pregnancy in preventing and ameliorating sleep, psychopathology and attachment with future child at post-partum was considered the primary outcome. A study that compared scores on the Edinburgh Postnatal Depression Scale (EPDS) in 132 women divided into cognitive-behavioral therapy for insomnia (N = 89) or control group (N = 43) before, during and after pregnancy was used. G-Power software estimated that 114 women in total would be needed to have an effect power of at least 80%.

   Women will be recruited primarily in the area of Bologna and Rome (Italy) and study's materials will be conserved in the Department of Biomedical and Neuromotor Sciences, University of Bologna (Italy).

   Screening: all interested women will be contacted for an appointment with a clinical psychologist for the screening, which will be conducted in a confidential space in a room at the Universities' Department involved (Department of Biomedical and Neuromotor Sciences, University of Bologna; Department of Human Sciences, Guglielmo Marconi University of Rome). These spaces will be used for all in-person contact with the participants (details below). Study's materials, including biological samples, will be conserved in a secured room in the Department of Biomedical and Neuromotor Sciences, University of Bologna for the whole duration of the study. All women will be asked to read and sign the informed consent before proceeding. Women will be evaluated through a widely used psychological structured interview (Structured Clinical Interview for DSM-5, SCID-5 in the brief version QuickSCID-5) and an interview about sleep. Furthermore, data on pregnancy and socioeconomic variables will be collected. Women will be asked to share, along with their consent, gynecological medical data on their health status (e.g. information on pregnancy). This face-to-face screening procedure will be conducted for checking inclusion criteria.

   The full sample will be divided in the following groups matched for age.
   1. Group A: control group of healthy pregnant women with no insomnia complaints (N=38);
   2. Group B: pregnant women complaining of subthreshold or clinical insomnia (N=76), further assigned to the following subgroups: Subgroup B1: psychological placebo intervention (N=38), Subgroup B2: CBT-I derived intervention (N=38).

   Insomnia complaints will be assessed through a validated questionnaire 'Insomnia Severity Index'. No insomnia complaints (Group A) vs insomnia complaints (Group B) will be operationalized using the cut-off of 7 (subthreshold insomnia). Group B will be randomly assigned to Subgroup B1 and to Subgroup B2.

   After the baseline interview, all women will be monitored longitudinally in 6 assessment evaluations:
   1. Baseline: between the 11th and the 15th week of pregnancy;
   2. Follow-up-1: after 6 weeks from baseline;
   3. Follow-up-2: after 12 weeks from baseline;
   4. Follow-up-3: 1-to-2-weeks after birth;
   5. Follow-up-4: 3-months post-partum;
   6. Follow-up-5: 6-monhts post-partum.

   For women who will be offered clinical treatment, baseline and follow-up-1 assessments will be conducted pre- and post-treatment.

   At three time points (Baseline, Follow-up 1, and Follow-up 5) an ecological-momentary-assessment (EMA) design will be used to collect data on sleep and emotions (sleep diary), sleep-wake parameters (actigraphy) and stress reactivity (salivary cortisol). Women will be asked, for each EMA week, to complete a sleep and emotion diary twice a day (in the morning and evening), to wear a wrist actigraph for 7 days, and to collect, on the first day of each EMA week, saliva samples through swabs. Saliva samples will be collected in the morning and the evening and will be used to evaluate salivary cortisol levels by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cortisol levels will be used as index of stress reactivity. Aliquots of morning salivary (1 assessment per person) will be used for the analysis of DNA methylation of the genes FKBP5, BDNF, and NR3C1, by Sequenom MALDI-TOF mass spectrometry, as potential biomarkers of prenatal poor sleep.

   The partner of each participant (n=114) will also be invited to take part to the study by filling out online questionnaire and sleep diaries for each assessment point detailed above.

Eligibility criteria: Inclusion Criteria:

1. age ≥ 18 yrs. old;
2. good knowledge of Italian language;
3. intention to continue pregnancy;
4. BMI ranging 18-30 (i.e., without underweight or obesity following international criteria; WHO, 2013);
5. ≤ 15th week of pregnancy at the time of recruitment.

Exclusion Criteria:

1. severe diagnosis of relevant somatic disorder;
2. smoking;
3. alcohol intake;
4. assumption of illegal drugs;

Primary outcomes:
measure: Stress reactivity
timeFrame: Twice a day (morning and evening) once at baseline; after 6 weeks from baseline; 6 months post-partum
measure: Sleep efficiency
timeFrame: One week at baseline; after 6 weeks from baseline; 6 months post-partum
measure: Depressive symptoms
timeFrame: Baseline; after 6 weeks from baseline; after 12 weeks from baseline; 1-to-2-week after birth; 3 months post-partum; 6 months post-partum
measure: Insomnia symptoms
timeFrame: Baseline; after 6 weeks from baseline; after 12 weeks from baseline; 1-to-2-week after birth; 3 months post-partum; 6 months post-partum
measure: Anxiety symptoms
timeFrame: Baseline; after 6 weeks from baseline; after 12 weeks from baseline; 1-to-2-week after birth; 3 months post-partum; 6 months post-partum
measure: Valence of affective states
timeFrame: Baseline; after 6 weeks from baseline; after 12 weeks from baseline; 1-to-2-week after birth; 3 months post-partum; 6 months post-partum
measure: Arousal of affective states
timeFrame: Baseline; after 6 weeks from baseline; after 12 weeks from baseline; 1-to-2-week after birth; 3 months post-partum; 6 months post-partum
measure: Emotion regulation
timeFrame: Baseline; after 6 weeks from baseline; 6 monhts post-partum
Secondary outcomes:
measure: Mothers' parenting stress
timeFrame: 1-to-2-week after birth; 3 months post-partum; 6 months post-partum
measure: Partners' insomnia symptoms
timeFrame: Baseline; after 6 weeks from baseline; after 12 weeks from baseline; 1-to-2-week after birth; 3 months post-partum; 6 months post-partum
measure: Children sleep difficulties
timeFrame: 1-to-2-week after birth; 3 months post-partum; 6 months post-partum
Other outcomes:
measure: Partners' sleep efficiency
timeFrame: One week at baseline; after 6 weeks from baseline; 6 monhts post-partum
measure: Fathers' parenting stress
timeFrame: 1-to-2-week after birth; 3 months post-partum; 6 months post-partum
measure: Daytime sleepiness
timeFrame: Baseline; after 6 weeks from baseline; after 12 weeks from baseline; 1-to-2-week after birth; 3 months post-partum; 6 months post-partum
Locations:
city: Bologna
country: Italy
facility: Department of Biomedical and Neuromotor Sciences, Physiology campus, University of Bologna, Bologna, Italy
Study officials:
affiliation: Department of Human Sciences, Guglielmo Marconi University, Rome, Italy
name: Chiara Baglioni, Professor
role: STUDY_DIRECTOR
References:
citation: Austin MP, Frilingos M, Lumley J, Hadzi-Pavlovic D, Roncolato W, Acland S, Saint K, Segal N, Parker G. Brief antenatal cognitive behaviour therapy group intervention for the prevention of postnatal depression and anxiety: a randomised controlled trial. J Affect Disord. 2008 Jan;105(1-3):35-44. doi: 10.1016/j.jad.2007.04.001. Epub 2007 May 8.
citation: First & Williams. QuickSCID-5. Raffaello Cortina Editore - Libro Raffaello Cortina Editore; 2020. https://www.raffaellocortina.it/scheda-libro/michael-b-first-janet-bw-williams/quickscid-5-9788832853629-3590.html
citation: Meneo D, Bacaro V, Buonanno C, Baglioni C. La valutazione del sonno in psicoterapia: una proposta di intervista clinica semistrutturata | Giovanni Fioriti Editore. Cognitivismo clinico. Published online November 9, 2023. https://www.fioritieditore.com/la-valutazione-del-sonno-in-psicoterapia-una-proposta-di-intervista-clinica-semistrutturata/