Sample
This study is a sub-study of a larger RCT, where perceived stress (assessed with the Perceived Stress Scale) was the primary outcome (BLINDED REFERENCE). The Stockholm Regional Ethics Committee approved the study (approval number 2012/400-31/4) and written informed consent was obtained from all participants. Participants were blinded to the study hypothesis and recruited through eight maternity health clinics (MHCs) in Stockholm County between 2014 and 2015. The inclusion criteria were being a woman with a history of depression and/or anxiety and/or early life adversity and/or current high levels of perceived stress. The details of study recruitment, procedures and eligibility have been described in detail in another publication (BLINDED REFERENCE). For the larger RCT that this study is part of, a letter of invitation was sent to 1647 primiparous women. Of those, 347 women were assessed for eligibility and 193 met the inclusion criteria and agreed to participate; 96 were randomized to the MBCP group and 97 to the Lamaze group, see below. Blood samples and HRV measures for the present study were collected from the first 60 participants that were included in the study (26 in the intervention and 34 in the control group). For further information on participation, see flowchart (Fig. 1). Trial registration: ClinicalTrials.gov ID: NCT02441595.
Procedure
Eligible participants were scheduled for an appointment at the MHC for HRV-registration and the baseline questionnaires were completed on. After baseline assessments, an independent administrator randomised the participants to either MBCP or Lamaze, according to a sequence generated in SPSS in blocks of 10.MBCP participants joined the program within two weeks after baseline assessment, and Lamaze participants joined this program at between three and five weeks after baseline assessment. At ten to twelve weeks after the baseline assessment both groups completed post-intervention assessments.
Intervention
The original 9-week MBCP program was developed in the USA and consists of nine 3-hour long weekly sessions, a full day retreat and a reunion (Bardacke, 2012). In the current trial we adjusted the curriculum to Swedish conditions (see the details about the adjustments in BLINDED REFERENCE).
Active control
In order to control for the effects of social support, psycho-education and child-birth preparation, the active control condition consisted of a Lamaze program that is widely available in Stockholm (for more details see BLINDED REFERENCE).
Outcome Measures
Perceived Stress Scale (PSS). The PSS contains fourteen items that are used to assess perceived stressful experiences (Cohen, 1983). A Swedish version has been translated and validated (Eklund, Bäckström, & Tuvesson, 2014).
Edinburgh Postnatal Depression Scale (EPDS). The EPDS contains ten items that are used to assess depressive symptoms (Cox, Holden, & Sagovsky, 1987; Levis et al., 2020; Rubertsson, Börjesson, Berglund, Josefsson, & Sydsjö, 2011).
Positive States of Mind (PSOM). The PSOM contains six items that are used to assess positive emotional and cognitive experiences.
Five-facet Mindfulness Questionnaire (FFMQ). The Swedish Version of the FFMQ contains 29 items that are used to assess five facets of mindfulness (Baer, Smith, Hopkins, Krietemeyer, & Toney, 2016; Lilja et al., 2011).
In the larger RCT of which this study is a part, we assessed internal consistency for all four scales (Cronbach alpha for PSS = .82, for EPDS = .85, for PSOM = .83, for FFMQ = .85 and FFMQ subscales = .82, .75, .84, .88, .84).
Serum markers
Prior to randomisation, at pregnancy week 20-25, as well as at post-intervention, at pregnancy week 30-35, the participants left blood samples at a health clinic laboratory. 5 ml of blood was collected from each participant and then left to cool down for 30-60 minutes in room temperature before being centrifuged for 10 minutes at 2400 x gravity. The serum from each tube was thereafter aliquoted into two separate tubes, and frozen at -20°C. The biological outcomes in this study included serum levels of Interleukin-10 (IL-10), Interleukin-6 (IL-6), Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α), osteocalcin and nine acute phase proteins (alpha-2-microglobulin (A2M), C-reactive protein (CRP), haptoglobin, serum amyloid P (SAP), procalcitonin (PCT), ferritin, tissue plasminogen activator (tPA), fibrinogen and serum amyloid A (SAA)). Serum levels were assessed by using a premixed, magnetic bead-based multiplex panel (BioRad, Hercules, CA, USA), according to the manufacturer instructions. Concentrations were imputed using Bio-Plex 200 Suspension Array System with Bio-Plex Manager 6.0 software (Hercules, CA, USA). Coefficients of variation were calculated for the manufacturer-provided analytical controls. Samples below the lower level of quantification (LLOQ) were assigned the value of the LLOQ/√2 for the analyses.
Heart rate variability
ECG assessment was carried at baseline and post-intervention, out in a supine position on a stationary bench. Three ECG electrodes were placed over the left fifth intercostal space, the right fifth intercostal space and over the manubrium. Once the ECG signal was acceptable, participants were informed that they should rest for 10 minutes, alone in the examination room, before the ECG would be recorded for minimum 5 minutes. Participants were instructed not to talk or move excessively, to turn off their mobile phones, and to relax as much as possible. The ECG-assessments were recorded at a sampling frequency of 1000 Hz and stored on a computer. Each 300 s ECG-recording was inspected for ectopic beats and artifacts, as well as for the correct identification of each R-peak by the software, and non-sinus beats and other artifacts were corrected by interpolation (Birkett, Kienzle, & Myers, 1991; Gao, Johansson, Hammarén, Nordberg, & Friberg, 2005). After preparation of the data, time domain measures of HRV such as SDNN (Standard Deviation of the N-N intervals) and RMSSD (Root Mean Square of the Successive Differences), were computed, as well as power spectral analysis of the frequency domain, that partitions the total variance (the “power”) of a continuous series of beats into its frequency components: Low Frequency (LF), 0.04–0.15 Hz, High Frequency (HF) 0.15–0.4 Hz, and the ratio of LF to HF (LF/HF) (Akselrod et al., 1981; Appel, Berger, Saul, Smith, & Cohen, 1989).
Statistical Analyses
Independent sample t-tests were used for parametrically distributed data on interval scale level. For non-parametric data the Mann-Whitney U test was used to compare groups. Variables on nominal levels were tested by Fisher´s exact test. Some of the variables were skewed and therefore transformed to their natural logarithm (ln) before analyses with parametric tests could be conducted. Those analytes that had more than 10% of values with LLOQ were transformed into binary variables, where 0 denoted “under LLOQ” and 1 denoted “over LLOQ”. Spearman rank correlations (Rs) were calculated to assess the correlations between the questionnaire target variables and blood sample target variables/HRV at baseline. Within group comparisons from pre- to post-intervention were carried out using either paired t-tests for parametric distributions or Wilcoxon signed-rank test for non-parametric distributions. Linear regression analyses (or multinomial logistic regression analyses for categorical variables) were conducted to assess whether there were any significant differences between the intervention and control group in the change of target variables (post-intervention values minus pre-intervention values). Due to the fact that the participating women entered the study (and hence, the pre-test) at different stages of pregnancy, the regression analyses were adjusted for pregnancy week since both serum inflammatory markers and HRV are considered to be related to gestation progress. The regression analyses for psychometric measures where not adjusted for pregnancy week, since pregnancy week was found not to be a confounder in the exploratory analyses. Only data from participants who completed the follow-up assessments was analyzed. All analyses were performed using Stata software (version 14.2).