Statistical analysis
The sample size calculation has previously been described in detail
(19). At 29–34 weeks of gestations we expected a mean difference of
7.75 (SD=16) in WHO-5 between the intervention group and the control
group. Based on a two-sample t-test and a two-sided significance level
of 0.05, 91 women are required in each treatment group to obtain a power
of 90%. A total of 300 women were planned to be randomised allowing for
a 13% drop out as a result of discomfort or complications and a further
30% drop out due to refusal to fill in the questionnaires.
To account for missing values under the assumption of Missing At Random
(MAR) and to adjust for potential baseline imbalances between the two
treatment groups, quantitative outcomes were analysed using constrained
linear mixed models considering scores measured baseline, 29–34 weeks
of gestation and eight weeks postpartum as outcomes (24). The fixed part
of the models included the interaction between group (intervention and
control) and time (baseline/29–34 weeks/eight weeks postpartum) with
the constraint that the means in the two groups were assumed equal at
baseline due to randomisation. The random part of the model included a
random intercept for each patient.
For each group and each time point, the proportion of women with EPDS
≥11 was estimated from a logistic regression model with parameters
estimated by weighted Generalised Estimating Equations (GEE) to account
for repeated measures and missing data (25). The weights were defined as
the inverse probabilities of being observed conditional on previous
measurements of EPDS (quantitative), treatment group and previous
missing value of EPDS and were estimated from a logistic regression
model. An unstructured correlation matrix was used as the working
correlation.
As specified in the protocol (19), analysis of WHO-5 was repeated based
on the sub group of women attending ≥75% of the sessions. In this
analysis, the linear mixed model was not constrained to assume equal
means at baseline as the randomisation is not valid for this group of
women.
Due to the large number of hypotheses tested, correction for multiple
testing was applied. The p-value corresponding to the comparison of the
secondary outcome (WHO-5 at eight weeks postpartum) was adjusted
accounting for the test of the primary outcome, there by multiplying the
p-value by 2 (False Discovery Rate method ). The remaining secondary
outcomes are presented uncorrected for multiple testning.