Results
Between 26/05/2015 and 14/08/2017, 1,182 women were screened for trial
eligibility at our antenatal assessment unit. A total of 304 women were
randomised, nine participants withdrew prior to the infusion, two did
not receive the infusion and one entered labour before the infusion. 292
participants received an infusion and 278 were included in the analysis.
The trial flow is shown in Figure 1.
The demographic and clinical characteristics of study participants at
baseline are presented in Table 1. Participants were enrolled into the
trial on average at 32 weeks gestational age. Approximately half of all
participants were anaemic at study entry. The first infusion was
received on average 11-12 days after screening.
The proportion of participants assigned to the two different trial doses
of IVI were not equivalent within a 5% margin at any time point (Table
2). More participants assigned to 500mg IVI required repeat infusions at
4 weeks post infusion compared to those assigned to 1000mg IVI (26/73
(36%) vs 5/67 (8%); estimated difference in proportions, 0.28, 90% CI
(0.18, 0.39)). Between 4 weeks post infusion and 6 months postpartum,
the difference between the groups reduced but the 90% confidence
interval did not lie within (-0.05, 0.05), therefore equivalence was not
achieved within a 5% margin (15/88 (17%) vs 9/67 (13%) at 6 months
postpartum; estimated difference in proportions 0.037, 90% CI (- 0.059,
0.133)) (Figure 2). The proportion of participants requiring a repeat
infusion increased over time in the 1000mg IVI group from 5/67 (8%) at
4 weeks post infusion to 14/70 (20%) at 12 months postpartum.
Equivalence was not achieved in the sensitivity analyses using linear
mixed models, GEEs with different correlation structures, participants
who received repeat infusions or were treated per protocol (Table S1)
and the secondary analysis of all randomised participants (Table S2).The
proportion of participants who required a repeat infusion at any time
during follow-up was also not equivalent (83/152 (55%) vs 34/126
(27%), estimated difference in proportions 0.288, 90% CI (0.191,
0.384)) ( Table S1).
Compared to participants assigned to 1000mg IVI, participants in the
500mg IVI received more than twice the repeat infusion rate prior to
delivery, after delivery and overall (0.81 (0.84) vs 0.40 (SD= 0.69),
Rate Ratio 2.05, 95% CI (1.45, 2.91), p < 0.001) (Table
3).
Participants who received 1000mg IVI had significantly higher ferritin
levels up to 6- months postpartum, compared to those receiving 500mg IVI
(Table 3). Similarly, serum iron and transferrin saturation were higher
in participants who received 1000mg IVI than participants who received
500mg IVI at 4 weeks post infusion, while transferrin was lower (Table
3). Between group differences had disappeared for all markers of iron
status by 12 months postpartum.
No serious adverse events were observed. Minor adverse events were
observed in 3% (n=8/276, 2 with missing data) of all participants
during the first infusion, including 5/126 participants (4%) who
received 1000mg iron (dizziness n=2, hypotension n=1, nausea n=1, chest
tightness n=1) and 3/150 participants (2%) who received 500mg iron
(nausea n=2, hypotension n=1). There was no difference between the
groups (Fisher’s exact test, p=0.48). No adverse events were observed on
subsequent infusions.
PPROM occurred in 6/121 participants in the 1000mg arm only. The
likelihood of other maternal complications did not differ between
participants who received 500mg and 1000mg IVI (Table 3). Similarly, no
difference was found between the length of gestation, neonatal outcomes,
or child neurodevelopment between the two doses (Table 3).
A post-hoc analysis of haemoglobin
levels indicated these were significantly higher in participants in the
1000mg IVI group compared to the 500mg IVI at 4 weeks post infusion (
Table S3). At each time point, the mean Hb level was in a range
indicating sufficiency (>115) in both the 500mg and 1000mg
IVI iron groups.