Strengths and Limitations
This study explored CVF cytokine trajectories throughout spontaneous
labor onset and considers symptom status, sub-categories of delivery and
time-dependent properties biomarkers. In addition, this study attempts
to address gestational age heterogeneity and suggests a pragmatic way
that could make diagnosis and prediction of spontaneous labor easier
with greater accuracy and at a lower cost. Timely detection of
spontaneous labor is fundamental to identify those mothers at higher
risk of delivering and plan appropriate management. Conversely,
predicting spontaneous delivery to identify women at low risk would
avoid the use of unnecessary and sometimes costly
interventions.31
Amongst the limitations to be acknowledged, the research design limits
the ability to establish real temporal relationships, which might
require further confirmation in a longitudinal setting following the
same women.
A common characteristic of cytokine data sets is undetectable values or
when concentrations exceed a certain threshold on the top of the
measurement scale, and thus the issue of “censored data” needs to be
addressed, which generally make statistical analysis challenging. The
literature recommends different methods to deal with censored
data.35 We used simple substitution for IL-1Ra (the
only cytokine with censored values) due to the large proportion of
censored values. However, simple substitution is not advisable as it may
lead to strongly biased results.36 To overcome this,
we performed multiple imputation using chained equations to account for
variability of missing data; we performed a sensitivity analysis of
complete-cases versus multiple imputed data and observed no significant
results discrepancies.