NMA results: dexamethasone vs. betamethasone
The geometry of the treatment networkis presented in Figure 2 ,
and the direct, indirect and NMA (mixed) effect estimations for the main
eight outcomes of the comparison dexamethasone vs. betamethasone are
presented in Figure 3 and Table 1 of Summary of
finding. We also present in the Appendix S5 the direct
comparison forest-plots, in Appendix S6 the summary of finding
tables of each corticosteroid vs. control, in Appendix S7 the
pairwise meta-analysis forest-plots by type of corticosteroid against
placebo and in Appendix S8 the NMA outputs and SUCRA values.
-Chorioamnionitis (6,698 patients, 15 studies)
Compared with placebo/no treatment (control), dexamethasone probably
increases chorioamnionitis but in one side of the confidence interval
could also reduce it: OR 1.46
(95%CI 0.81-2.66). On the contrary betamethasone reduces
chorioamnionitis: OR 0.63 (95%CI 0.41-0.95). The test for subgroup
differences by corticosteroid type showed this disparity (P= 0.010, I²
84.2%).
Compared with betamethasone, dexamethasone probably reduces
chorioamnionitis but in one side of the CrI is slightly detrimental:OR 0.70 (95%CrI 0.45-1.06), moderate-CE . We found
serious incoherence between direct and indirect evidence (Ratio of OR
[ROR] 3.18 [95%CI 1.26-8.02]).
-Endometritis/puerperal sepsis (4,030 patients, 10 studies)
Dexamethasone may increase endometritis/puerperal sepsis and
betamethasone probably have little or no effect against control: OR 1.93
(95%CI 0.8534.41) and 0.94 (95%CI 0.47-1.87), respectively (Test for
subgroup differences suggest disparities; P: 0.16, I² 49.8%).
There was no report of direct evidence regarding this outcome. Indirect
evidence suggest that compared with betamethasone, dexamethasone may
increase endometritis/puerperal sepsis, but in one side of the CrI is
protective: OR 2.04 (95%CrI 0.72-6.06), low-CE .
-Neonatal Death (8697 patients, 23 studies)
Both dexamethasone and betamethasone reduce neonatal death against
control: OR 0.60 (95%CI 0.37-0.94) and OR 0.57 (95%CI 0.39-0.80),
respectively (Test for subgroup differences shows no disparity; P: 0.81,
I² 0%). We found no incoherence; ROR 1.15 (95%CI 0.44-2.96), therefore
we considered the NMA evidence the most reliable estimation. Compared
with betamethasone, dexamethasone probably has no effect on neonatal
death, but the CrI is compatible with beneficial or detrimental effect:OR 1.05 (95%CrI 0.62-1.84), moderate-CE .
-Foetal death (3857 patients, 13 studies)
Dexamethasone may reduce foetal death and betamethasone probably have
little or no effect against control: OR 0.86 (95%CI 0.32-2.16) and 1.05
(95%CI 0.58-2.15), respectively (Test for subgroup differences shows no
disparity; P: 0.70, I² 0%). There was no report of direct evidence
regarding this outcome. Indirect evidence suggest that compared with
betamethasone, dexamethasone may reduce foetal death, but the CrI limits
is compatible with large beneficial or detrimental effect: OR
0.81 (95%CrI 0.24-2.41), low-CE .
-Respiratory distress Syndrome (9784 patients, 30 studies)
Both dexamethasone and betamethasone may reduce neonatal death against
control: OR 0.64 (95%CI 0.47-0.90) and 0.47 (95%CI 0.35-0.60),
respectively (Test for subgroup differences suggest disparities; P:
0.11, I² 54.7%).
We found no serious incoherence; ROR 1.14 (95%CI 0.71-2.75), therefore
we considered the NMA evidence the most reliable estimation. Compared
with betamethasone, dexamethasone probably increases RDS but the CrI is
compatible with a small protective effect: OR 1.38 (95%CrI
0.96-2.11), moderate-CE .
- Neurodevelopmental
disability (2628 patients, 3 studies)
We did not find direct evidence for betamethasone vs. placebo.
Dexamethasone may reduce neurodevelopmental disability against control:
OR 0.39 (95%CI 0.01-8.08).
Compared with betamethasone, dexamethasone probably has no effect on
neurodevelopmental disability, but the CrI is compatible with large
beneficial or detrimental effect: OR 1.14 (95%CrI 0.24-13.86). Two of
the included studies had rare events. The frequentist analysis suggested
more precise and reliable estimation an OR 1.03 (95%CI
0.80-1.33), moderate-CE .
-Intraventricular haemorrhage (IVH) (7449 patients, 17 studies)
Both dexamethasone and betamethasone reduce IVH: OR 0.473 (95%CI
0.281-0.738) and 0.381 (95%CI 0.191-0.668), respectively (Test for
subgroup differences shows no disparity; P: 0.88, I² 0%).
We found no serious incoherence; ROR 1.54 (95%CI 0.57-4.16). The NMA
evidence suggested that compared with betamethasone, dexamethasone may
reduce IVH but the CrI is compatible with beneficial or detrimental
effect: OR 0.812 (95%CrI 0.420-1.427), low-CE. However, we found mild
heterogeneity (I2 31%) and important subgroup
differences by corticosteroid type (I² 63.5%).
Considering the very high risk of attrition bias (43% of non-analysed
infants), the unique marked effect favouring dexamethasone of the study
Elimian 200746 and the
incoherence that this study had generated, we performed a post-hoc
sensitivity analysis excluding it. Both the heterogeneity and subgroup
differences changed to an I² of 0%. The new estimation, stilllow-CE , OR 1.04 (95%CrI 0.56-1.78) was more
consistent with the indirect evidence (ROR 1.14 (95%CI 0.51-2.57) and
therefore we considered it as the most reliable estimation (forest-plots
in Appendix S5 ).
-Mean birthweight (8645 patients, 23 studies)
Both dexamethasone and
betamethasone have no effect on birthweight against control: MD -17.04gr
(95%CI -75.48; 41.41) and -9.74 gr. (95%CI -43.11; 23.63),
respectively (Test for subgroup differences shows no disparity; P: 0.80,
I² 0%). We found no serious incoherence; ROR 1.15 (95%CI 0.44-2.96)
and both direct and indirect evidence were considered as high certainty
evidence, therefore we considered the NMA evidence the most reliable
estimation. Dexamethasone has no effect mean birthweight:mean difference
+ 5.29gr (95%CrI -49.79, 58.97) high-CE .