Background
Pregnancy and childbirth are significant events in many women’s lives, that often entail abrupt lifestyle changes in addition to hormonal and physiological alterations [
10]. The prevalence of mental health problems, especially depressive symptoms, is increased during this vulnerable time of life. The rate of women who suffer from depressive disorders has been reported to be 10% during pregnancy and 13% postpartum (World Health Organization [
49]). In addition to the mental health impact on women, depression during pregnancy and in the postpartum period – together referred to as perinatal depression (PND) – also affects the health and wellbeing of the child [
25]. Despite its well-documented health consequences, PND often remains undetected and untreated [
17].
Exposure to stressful life events [
42] and stress in everyday life, such as work-related stress [
16] has been found to increase the risk of PND. Indeed, life stress overall has been found to incur a medium to strong risk for PND [
26].
Apart from an array of well documented cognitive, affective, and somatic symptoms (WHO [
48]) depression as well as stress are associated with physiological changes, such as reduced heart-rate variability (HRV) and activation of the inflammatory response system [
27,
35,
36]. Psychophysiological research has shown that HRV can be used to index cardiac vagal tone, which represents the contribution of the parasympathetic nervous system to cardiac regulation. HRV can be impacted by self-regulation at the cognitive, emotional, social, and health levels [
30].
Importantly, reduced HRV in pregnant women with depression has been related to abnormal uterine artery blood-flow and lower infant birth weight [
45]. Also, pregnant mothers with previous anxiety disorders have been shown to have reduced HRV [
7,
21,
45].
During pregnancy, the woman’s body undergoes extensive changes in immune system adaptation and inflammatory response, which can be detected through blood samples [
8,
29]. Complex adaptations are made to protect the fetus against pathogens as well as to adjust the mother´s immunological response in order to prevent rejection of the fetus, which lead to increases in a number of inflammatory markers during the progression of pregnancy [
8,
29]. Moreover, inflammation has been reported to increase the risk of depression and stress-related disorders [
14,
31,
37], as well as predict recurrent major depression episodes [
51]. Negative maternal emotions in childbirth have been associated with an increase in pro-inflammatory cytokines of both the mother and the infant [
22], even if no single biomarker for PND has been identified to date [
9,
39].
In recent decades, the use of Mindfulness Based Interventions (MBIs) in clinical settings, and research regarding their effects on various health-related outcomes have increased rapidly. Mindfulness practice was initially secularized and brought to clinical settings by Jon Kabat-Zinn with the Mindfulness Based Stress Reduction program (MBSR) [
44]. Taken together, the use of MBIs is wide spread, and the preliminary research in this field shows that antenatal MBIs are feasible and appreciated, and systematic reviews motivate further research in a field that shows promising results [
4,
18,
46].
Some of the MBIs have been tailored specifically for pregnant women and their partners and assessed in terms of a variety of outcomes in iterated pilot studies, with only a few with a randomised controlled design and an active control condition [
34]. A recently published systematic review [
3] and a meta-analysis [
18] have concluded that there is sufficient evidence for the use of mindfulness interventions for anxiety, stress and depression reduction in the perinatal period, but that research of the effects on other pregnancy-related outcomes is yet insufficient.
Some studies have documented physiological effects of mindfulness on immune function [
13,
15], and on HRV [
38], However, a recent meta-analysis on mindfulness based interventions on biomarkers showed mixed and inconclusive results, particularly due to the lack of large, rigorously conducted RCTs [
41].
In summary, MBIs may potentially have an effect on HRV and inflammatory biomarkers, and our previous study showed significant effects on PND and perceived stress. Therefore, the aim of this study was to assess the effects of a Mindfulness Based Childbirth and Parenting (MBCP) intervention on HRV and serum inflammatory marker levels, through an RCT study design with an active control group. The active control consisted of a Lamaze childbirth program. This method has been developed initially by Dr Fernand Lamaze [
40], and is widely used as childbirth preparation in the Swedish context, where the present study was conducted. The method includes focused breathing techniques, muscle relaxation, and focus practices, and has been shown in a recent meta-analysis to carry positive effects on the length of labor, alleviate labor pain and reduce post-partum bleeding [
50]. However, the aim of Lamaze is mainly to assist women in the physical side of labor and does not focus particularly on the common psychological challenges of pregnancy and childbirth.
The study hypotheses were that: 1) the intervention group, in comparison with the active control group, will have a larger increase of HRV; and 2) the intervention group, in comparison with the active control group, will have a smaller increase in serum inflammatory markers.
Results
Background of participants
Table
2 displays the descriptive statistics and group comparisons for demographic variables and shows a significant difference in pregnancy week at pre-test (
p=0.0472). There were no significant baseline differences between groups in age, civil status, nationality, education, income or prescribed drug use.
Table 2
Socio-economic background characteristics of all participants (n=60)
Age, years |
Mean | 31.6 | 32.9 | t = -1.435 | 85 | 0.155 |
SD | 3.93 | 4.70 | | | |
Civil status | n (%) | n (%) | Fisher´s exact test | | 1.000 |
Single | 0 (0%) | 1 (2%) | | | |
Co-living | 25 (60%) | 26 (58%) | | | |
Married | 17 (40%) | 17 (38%) | | | |
Living apart | 0 (0%) | 1 (2%) | | | |
Nationality | | | Fisher´s exact test | | 0.814 |
Swedish | 37 (88%) | 38 (84%) | | | |
Swedish & other | 2 (5%) | 4 (9%) | | | |
European | 2 (5%) | 1 (2%) | | | |
Non-European | 1 (2%) | 2 (4%) | | | |
Education | | | Fisher´s exact test | | 1.000 |
Elementary | 0 (0%) | 0 (0%) | | | |
Secondary | 7 (17%) | 8 (18%) | | | |
College | 35 (83%) | 37 (82%) | | | |
Pregnancy week at pre-test |
Mean | 24.3 | 22.9 | z=1.98 | | 0.0472 |
SD | 3.85 | 3.77 | *Mann-Whitney | | |
Household income/month | | | Fisher´s exact test | | 0.223 |
< 25 000 SEK | 0 (0%) | 0 (0%) | | | |
25 - 40 000 SEK | 5 (12%) | 5 (11%) | | | |
40 - 60 000 SEK | 17 (40%) | 11 (24%) | | | |
> 60 000 SEK | 20 (48%) | 29 (64%) | | | |
Prescribed drug use | | | Fisher´s exact test | | 0.377 |
None | 25 (60%) | 33 (73%) | | | |
Other medication | 12 (29%) | 9 (20%) | | | |
ADHD medication | 0 (0%) | 1 (2%) | | | |
SSRI | 4 (10%) | 2 (4%) | | | |
Sedatives | 1 (2%) | 0 (0%) | | | |
Baseline differences between groups in psychometric measures, serum markers and HRV
No significant baseline differences between groups in outcome variable values were found, apart from a-2 microglobulin and IL-6 where higher levels were found in the intervention group at baseline with p-value = 0.025 and 0.036 respectively.
Correlations between psychometric measures and serum markers/HRV at baseline
There was no correlation found between any of the questionnaire target variables and blood sample target variables / HRV at baseline or at post-intervention (analysis performed for all participants together).
Within group changes
Table
3 displays the within group changes in the psychometric measures between different time points.
Table 3
Within group changes, psychometric measures. Wilcoxon signed-rank test
PSS | 27.774 (8.492) 28 | 21.774 (6.835) 22 | ≤ 0.001 | - 0.68 | 25.275 (7.049) 26 | 22.525 (9.047) 21 | 0.0050 | - 0.44 |
EPDS | 9.967 (5.136) 10 | 6.742 (3.812) 6 | 0.0010 | - 0.60 | 8.475 (5.179) 9 | 7.425 (5.629) 7.5 | 0.0484 | - 0.31 |
FFMQ | 87.200 (14.175) 86 | 98.233 (12.266) 98 | ≤ 0.001 | 0.80 | 93.425 (12.796) 91 | 99.6 (14.836) 99 | ≤ 0.001 | 0.59 |
In the intervention group, the within-group comparisons of the psychometric variables from baseline to post-intervention showed significant decreases in perceived stress (PSS) scores (p≤0.001), and perinatal depression (EPDS) scores (p≤0.001) and significant increases in mindfulness (FFMQ) scores (p≤0.001).
In the control group, the within-group comparisons of the target variables from baseline to post-intervention showed a significant decrease in PSS scores (p=0.005) and EPDS scores (p=0.048) and significant increases in FFMQ scores (p≤0.001).
Table
4 displays the within group changes in the inflammatory serum markers between different time points.
Table 4
Within group changes, serum markers. 1=Paired t-test, 2=Wilcoxon signed-rank test
A2M1 | 99209 (113106) 75156 | 145611 (196816) 48317 | 0.299 | | 60174 (65295) 41501 | 88612 (158265) 36290 | 0.138 | |
Hapto1 | 55286 (74169) 30459 | 170919 (418747) 24428 | 0.0412 | 0.30 | 29816 (36033) 19814 | 77298 (159572) 24015 | 0.0173 | 0.35 |
CRP2 | | N/A | 0.564 | | N/A | N/A | 0.527 | |
SAP2 | 1684 (1912) 1153 | 2970 (3269) 1532 | 0.0319 | 0.42 | 1189 (1302) 711 | 2075 (2922) 910 | 0.0428 | 0.35 |
PCT1 | 10989 (4555) 9586 | 10877 (5190) 10120 | 0.673 | | 12657 (6710) 10730 | 13602 (6866) 12473 | 0.141 | |
Ferr1 | 37687 (57439) 14300 | 25077 (20970) 22368 | 0.796 | | 45330 (62636) 18732 | 35411 (46080) 24513 | 0.576 | |
tPa2 | 5162 (4302) 3346 | 8419 (8161) 7142 | 0.0124 | 0.49 | 6935 (4998) 3939 | 8934 (5481) 9505 | ≤ 0.001 | 0.59 |
Fibri1 | 5970 (2034) 5198 | 6442 (2584) 5782 | 0.227 | | 6920 (2398) 5948 | 7544 (2567) 7324 | 0.0220 | |
SAA1 | 1477 (1189) 953 | 1673 (1312) 1326 | 0.262 | | 2330 (2051) 1478 | 2652 (2476) 1591 | 0.161 | |
Osteo2 | 1606 (1197) 2286 | 2872 (2434) 1641 | ≤ 0.001 | 0.79 | 1338 (1208) 977 | 1991 (1942) 1128 | ≤ 0.001 | 0.71 |
IL-1β2 | N/A | N/A | 0.317 | | N/A | N/A | 1.0000 | |
IL-62 | N/A | N/A | 0.480 | | N/A | N/A | 0.317 | |
IL-102 | N/A | N/A | N/A | | N/A | N/A | 0.157 | |
TNF- α2 | N/A | N/A | 0.706 | | N/A | N/A | 0.480 | |
In the intervention group, the within-group comparisons of the serum variables from baseline to post-intervention showed significant increases in serum levels of haptoglobin (p=0.041), serum amyloid P (p=0.032), tissue plasminogen activator (p=0.012) and osteocalcin (p≤0.001).
In the control group, significant increases from baseline to post-intervention serum levels of haptoglobin (p=0.017), serum amyloid P (p=0.043), tissue plasminogen activator (p≤0.001), fibrinogen (p=0.022) and osteocalcin (p≤0.001) were found.
No HRV parameters showed significant changes from baseline to post-intervention, neither in intervention- nor in control group (data not shown).
Between group comparisons
Table
5 displays the differences between the intervention and control group in the change of target variables (post-intervention values minus pre-intervention values). The MBCP group reported a larger reduction in perceived stress (
F(1, 69)= 4.54, adj
R2=0.0481,
p=0.037) and a larger increase in five facets of mindfulness (
F(1, 69)= 4.52, adj
R2=0.0485,
p=0.037). No other target variables showed significant differences between the intervention and control group.
Table 5
Between group changes, (post-intervention values minus pre-intervention values). 1=linear regression, 2=multinomial regression
Serum markers (n=46) | F (2, 57) | | | | | | |
A2M1 | 0.18 | -0.0284 | | | 0.605 | | 0.695 |
Hapto1 | 0.99 | -0.0005 | | | 0.429 | | 0.315 |
CRP2 | | | 1.515 | 0.299 | 0.107 | | 0.034 |
SAP1 | 0.43 | -0.0195 | | | 0.610 | | 0.496 |
PCT1 | 2.54 | 0.0495 | | | 0.495 | | 0.050 |
Ferr1 | 0.26 | -0.0256 | | | 0.756 | | 0.488 |
tPa1 | 0.47 | -0.0183 | | | 0.340 | | 0.780 |
Fibri1 | 1.46 | 0.0154 | | | 0.914 | | 0.101 |
SAA1 | 1.74 | 0.0246 | | | 0.933 | | 0.073 |
Osteo1 | 6.55 | 0.1582 | | | 0.160 | | 0.003 |
IL-1β2 | | | 1.034 | -0.238 | 0.428 | | 0.040 |
IL-62 | | | -1.735 | -0.101 | 0.152 | | 0.365 |
IL-102 | | | 16.906 | 0.361 | 0.996 | | 0.120 |
TNF- α2 | | | 0.204 | 0.00448 | 0.800 | | 0.966 |
HRV |
SDNN1 (n=56) F (2, 53) | 0.69 | -0.0114 | | | 0.757 | | 0.249 |
RMSS1 (n=49) F(2, 46) | 0.74 | -0.0108 | | | 0.288 | | 0.481 |
LFpow1 (n=52) F(2, 49) | 0.94 | -0.0025 | | | 0.190 | | 0.634 |
LFnorm1 (n=58) F(2, 55) | 2.06 | 0.0358 | | | 0.805 | | 0.060 |
HFpow1 (n=49) F(2, 46) | 1.12 | 0.0051 | | | 0.748 | | 0.169 |
HFnorm1 (n=56) F(2, 53) | 2.10 | 0.0386 | | | 0.505 | | 0.080 |
LF/HFpow1 (n=46) F(2, 43) | 0.35 | -0.0297 | | | 0.951 | | 0.410 |
Questionnaires (n=71) | F (1, 69) | | | | | | |
PSS1 | 4.54 | 0.0481 | | | 0.037 | 0.22 | N/A |
EPDS1 | 3.92 | 0.0406 | | | 0.052 | | N/A |
FFMQ1 | 4.52 | 0.0485 | | | 0.037 | 0.23 | N/A |
Discussion
In this study, no significant changes in our primary outcomes, inflammatory serum markers or HRV-measures, were found.
However, in line with the results from the main study, participants randomized to MBCP reported a significantly larger reduction in perceived stress and a significantly larger increase in mindfulness, compared to participants randomized to Lamaze. The finding of significant differences between groups in reductions in PND [
34] were not replicated in this sub-study. Nevertheless, the main purpose of this sub-study was not to assess between-group differences in changes in self-report measures.
This study is the first one to compare the effects of MBCP with an active control group not only on psychological outcomes, but also on physiological outcomes. The lack of significant effects of MBCP on inflammatory serum markers and HRV parameters found in this study are in line with the results reported in a recent review and meta-analysis [
41].
A normal pregnancy is related to remarkable changes in the immune system. Complex adaptations are made to protect the fetus against pathogens as well as to adjust the mother´s immunological response in order to prevent rejection of the fetus [
8,
29]. Due to this, the results from the current study on inflammatory serum markers can also be interpreted as a normal immunological shift that occurs in pregnancy and hence explain the lack of significant differences between MBCP and Lamaze. Both groups showed significant increases in haptoglobin, serum amyloid P, tissue plasminogen activator and osteocalcin, which can probably be explained by normal changes over time during pregnancy [
8]. In addition to changes in the immune system, a normal pregnancy is also related to an increase in sympathetic tone as the gestation progresses [
19,
23]. This may in turn result in altered HRV parameters [
28,
47], which may have rendered eventual changes from the intervention undetectable in the present study.
The findings on larger reduction in perceived stress and larger increase in mindfulness in the MBCP group compared to the Lamaze group, are in line with previous findings [
4]. However, the present study did not confirm our hypothesis that the MBCP program would incur greater positive impact on the stress-and depression-related physiological variables studied. This may be explained by that the control intervention - the Lamaze childbirth program - also has physiological impacts for the pregnant women, as has been demonstrated in a meta-analysis [
50].
Limitations of the study
This study has both limitations and strengths. A strength is the randomization of participants and the use of an active control intervention. However, we were not able to conduct a sample size calculation for the present study, due to the scarcity of other studies in this research field. Therefore, we cannot be certain that the lack of detectable differences between the groups in terms of biomarkers were due to the lack of actual changes in HRV and inflammatory parameters, or due to lack of statistical power. Due to the large number of statistical analyses conducted in the study, significant changes in certain variables should be interpreted with caution.
Future research
In this study, it was not possible to assess if some of the changes that were detected in biomarkers over time were due to the interventions or if they were naturally occurring during pregnancy. Therefore, it may be of interest to conduct future studies where a third arm with no intervention is included. Also, future studies may need to include larger samples, and the present study findings may be used as a basis for a future sample size calculation. Based on for example the CRP outcome in this study, we have been able to conduct a post hoc power calculation (4% change in intervention group vs. 0% change in control group), which gives 24.4% power.
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