Statistical analysis
All outcomes were analysed according to a predefined analysis strategy
that was conducted in collaboration with our clinical epidemiologist
(JGB).
For our main outcome, sensitivity and subgroup analyses on the
difference in severity of HDFN between two subsequent pregnancies, a
Wilcoxon Signed-Rank test was used. With this test, the number of
positive differences in severity (+1 to +3 disease categories), negative
differences (-1 to -3) and ties are ranked.
Differences in severity of HDFN between two non-paired groups were
analysed with a multinomial logistic regression. In other, non-paired
analyses, the Pearson’s Chi-square test or logistic regression (or
Fisher’s exact test if appropriate) was used for the comparison of
proportions. Comparisons of non-parametric outcomes were analysed with
the Mann-Whitney U test. A sensitivity analysis was performed among
patients in whom all the information on disease outcome was available
and disease severity was thus not imputed. As the mechanism and thus
severity of HDFN might be different if RhD antibodies are developed
after giving birth to a RhD-positive child and thus after receiving
anti-D at least twice (group A), or in the first pregnancy at risk for
immunization (group B), a subgroup analysis was performed in these
groups.
In order to identify factors possibly predicting severe HDFN (IUT or
death) in a subsequent pregnancy for counselling purposes, a prediction
model was constructed including variables known or thought to be
associated with HDFN severity from the literature, the potential
predictors. All potential predictors with a P -value<.25
in univariate analysis were included in a multivariate logistic
regression model. The prediction model was further improved by applying
manual backward selection, excluding the variable with the highestP -value at every step. Eventually, all variables with aP -value<.1 remained in the final prediction model.
RESULTS