Assessment of risk of bias and quality of evidence
The methodological quality of the included studies was assessed by two
independent reviewers (A.P and S.S..) using the Newcastle Ottawa scale.
The scale incorporates domains that include assessment of selection of
study groups, comparability of groups and methods ascertainment of the
outcome of interest. A point is awarded in a 9-point based system. For
the purposes of the present systematic review the two points that are
awarded for comparability of groups refer to differences in baseline
gestational age at assessment of serum LDH and in maternal age.
Quality of evidence was evaluated under the Grading of Recommendations
Assessment, Development and Evaluation (GRADE) framework, ranging from
very low to high. More specifically, credibility of evidence was
assessed by taking into account the following domains: study
limitations, directness, consistency, precision and publication bias. In
particular, study limitations were evaluated based on risk of bias
assessments (NOS score), while directness was judged using the PICOS
(population, intervention, comparison, outcome, study type) approach. To
assess consistency and precision, clinically important effects were
defined as serum LDH differences of ≥100 U/L, indicating a range of
equivalence from -50 to 50 U/L. In this context, consistency referred to
the agreement of 95% confidence and prediction intervals for each
outcome in relation to clinically relevant effects, while precision
assessment was made by taking into account whether 95% CI extended into
the range of equivalence.