80176

2017
JHLXXX10.1177/0890334416680176Journal of Human LactationAsztalos et al.

Original Research
Journal of Human Lactation

Enhancing Human Milk Production

2017, Vol. 33(1) 181­–187
© The Author(s) 2017
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DOI: 10.1177/0890334416680176

Preterm Infants: Results From the journals.sagepub.com/home/jhl

EMPOWER Trial

Elizabeth V. Asztalos, MD, MSc, FRCPC1,

Marsha Campbell-Yeo, PhD2, Orlando P. da Silva, MD3,
Shinya Ito, MD4, Alex Kiss, PhD5, and David Knoppert,
MScPhm6, for the EMPOWER Study Collaborative Group*

Abstract
Background: Mothers of preterm infants often are at risk of expressing an inadequate amount of milk for their infants and
the use of galactogogues is often considered. Domperidone is a widely used galactogogue with little information available to
guide clinicians regarding initiation, timing, and duration of treatment.
Research aim: The primary objective of this study was to determine whether administration of domperidone within the
first 21 days after delivery would lead to a higher proportion of mothers achieving a 50% increase in the volume of milk at
the end of 14 days of treatment compared with mothers receiving placebo.
Methods: Eligible mothers were randomized to one of two treatment arms: Group A—domperidone 10 mg orally three
times daily for 28 days; or Group B—placebo 10 mg orally three times daily for 14 days followed by domperidone 10 mg
orally three times daily for 14 days.
Results: A total of 90 mothers of infants ≤ 29 weeks gestation were randomized. Mean milk volumes at entry were similar
for both groups. More mothers achieved a 50% increase in milk volume after 14 days in Group A (77.8%) compared with
Group B (57.8%), odds ratio = 2.56, 95% confidence interval [1.02, 6.25], p = .04.
Conclusion: A greater number of mothers experienced a 50% or more increase in human milk volume, but the absolute
increase in milk volume was modest.

Keywords
breastfeeding, breast milk expression, galactogogues, human milk, human milk production, lactation difficulties, milk supply,
randomized controlled trials

Background Speight, & Avery, 1982). These characteristics have prompted

The use of mother’s own milk for infants born very preterm
has a positive effect in reducing potential serious neonatal
morbidities and also contributes to improvements in neurode-
velopmental outcomes (Abrams, Schanler, Lee, & Rechtman,
2014). However, the mothers of these infants are often at risk
of expressing an inadequate amount of milk for their infants
(Henderson, Hartmann, Newnham, & Simmer, 2008). For
these mothers, the use of galactogogues is often considered
(Forinash, Yancey, Barnes, & Myles, 2012). Domperidone is
a widely prescribed galactogogue not approved at this time by
any health authority for this use (Gabay, 2002). Its character-
istics prevent it from crossing the blood–brain barrier and
causing the extrapyramidal effects seen with other galacto-
gogues such as metoclopramide (Brogden, Carmine, Heel,
widespread use of the medication worldwide (Grzeskowiak,
Lim, Thomas, Ritchie, & Gordon, 2013; Smolina, Morgan,
Hanley, Oberlander, & Mintzes, 2016). However, there is a
paucity of research to augment the information on the galac-
togogue properties, safety, and efficacy of domperidone.
EMPOWER was a multicenter, double-masked, random-
ized controlled trial with an intention-to-treat analysis
(Asztalos et al., 2012). Its primary aim was to determine
whether administration of domperidone, within the first 21
days after delivery, would lead to a higher proportion of
mothers having a 50% increase in the volume of expressed
milk at the end of 14 days of treatment compared with moth-
ers receiving placebo. A secondary aim was to determine if a
4-week (28 day) treatment approach compared with a 2-week
(14 day) approach yielded a higher proportion of mothers
182 Journal of Human Lactation 33(1)

with an overall increase in expressed milk volumes. However,

enrollment had to stop when recruitment fell to a rate too low
for completion of the study.
Methods
Design
EMPOWER was a multicenter, double-masked, randomized
controlled trial with an intention-to-treat analysis.
Sample
The inclusion criteria were designed to identify those moth-
ers early postdelivery at higher risk of not being able to pro-
duce and/or maintain a supply of milk for their infants.
Mothers were eligible if their preterm infants were born ≤
29 completed weeks gestation (230/7–296/7 weeks), were 8 to
21 days postdelivery, were pumping a minimum of six times
a day in the 4 days prior to study entry, and were experienc-
ing a milk volume that was < 150 ml/kg/d (based on their
infant’s birthweight) during the 72-hour period prior to
study entry or a maternal report of milk volume reduction by
more than one-third from a peak volume of the previous 72
hours. The reported reduction of milk volume was con-
firmed by lactation support personnel at the center. In the
case of mothers with twins, the estimated fluid volume to be
produced was based on the weight of the larger twin. One
year into the study, the inclusion criteria were felt to be too
restrictive and were modified to 250 ml/kg/d or experienc-
ing a milk volume reduction of 20% or more from a peak
volume during the 72-hour period prior to study entry. In the
case of mothers with twins, the estimated fluid volume to be
produced was based on the combined weight of the twins.
Mothers could be identified in the neonatal intensive care
unit as early as Day 4 until Day 18 postdelivery. Additional
counseling and support by the lactation consultant with
Key Messages
•• There is a paucity of research to best guide cli-
nicians as to dose, timing of administration,
and duration of treatment of domperidone in
mothers of preterm infants.
•• Domperidone was effective in supporting more
mothers to increase their milk volume starting
as early as 8 days postdelivery.
•• Starting mothers on domperidone 2 weeks later
was similarly effective in supporting mothers
to increase their milk volume.
•• No serious adverse effects or evidence of pro-
longed Q-Tc were observed in this study.
respect to nonpharmacologic techniques were offered. If
there was no response to the techniques, the mother was
considered eligible for the trial.
Exclusion criteria included known or suspected cardiac
dysrhythmias (tachyarrhythmia, Q-Tc prolongation) or
receiving an anti-arrhythmic medication; current mastitis;
previous breast surgery (augmentation, reduction, nipple
piercing); chronic or debilitating illness; abnormal liver func-
tion; gastric abnormalities (gastrointestinal hemorrhage,
blockage, or currently treated acid reflux); human immunode-
ficiency virus; prolactin-releasing pituitary tumor; receiving
medications known to alter the metabolism and pharmacoki-
netics of domperidone (e.g., oral “azole” antifungals, macro-
lides, monoamine oxidase inhibitors) or medications that
have dopaminergic or antidopaminergic activity or affect pro-
lactin levels; mother of higher order pregnancies (triplet or
higher); and cigarette smoking.
The research ethics committee of each center approved
the study protocol. The first author and the biostatistician
took responsibility for the accuracy and completeness of the

1
Department of Newborn and Developmental Paediatrics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
2
Izaak Walton Killam Health Centre, Dalhousie University, Halifax, NS, Canada
3
Perinatal and Women’s Health, London Health Sciences Centre, Western University, London, ON, Canada
4
Division of Clinical Pharmacology & Toxicology, Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
5
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
6
School of Pharmacy, University of Waterloo, Kitchener, ON, Canada

*EMPOWER Study Collaborative Group (number of participants in parentheses): London Health Sciences Centre (7), London, ON: Orlando da Silva,
Nicola Geoghegan-Morphet; Hamilton Health Sciences Centre (4), Hamilton, ON: Christoph Fusch, Geoff Travis; Sunnybrook Health Sciences Centre
(36), Toronto, ON: Elizabeth Asztalos, Afsheen Ayaz; Jewish General Hospital (17), Montreal, PQ: Lajos Kovacs, Sandy Ho; Sainte-Justine Hospital (8),
Montreal, PQ: Annie Janvier, Julie Lavoie; Centre Hospitalier Universitaire de Quebec (6), Quebec City, PQ: Georges Cauoette, Mylene LeBlanc; Foothills
Medical Centre (3), Calgary, AB: Abhay Lodha, Linda Lavoie; Everett Chalmers Regional Hospital (1), Fredericton, NB: Barbara Bulleid, Judy Neal; Izaak
Walton Killam Health Centre (8), Halifax, NS: Doug MacMillan, Balpreet Singh, Marsha Campbell-Yeo, Kim Caddell.

Date submitted: September 8, 2016; Date accepted: October 30, 2016.

Corresponding Author:
Elizabeth V. Asztalos, MD, MSc, FRCPC, Department of Newborn and Developmental Paediatrics, Sunnybrook Health Sciences Centre, University of
Toronto, M4-230, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
Email: elizabeth.asztalos@sunnybrook.ca
Asztalos et al. 183
reported data. All the mothers who participated provided a
written informed consent before being enrolled. Because the
study was using an off-label indication for domperidone, the
study was conducted under the Food and Drug Act of Health
Canada.
Setting
EMPOWER was conducted in eight level 3 neonatal inten-
sive care units across Canada. Using a 24 hour/day web-
based randomization service at the coordinating center,
mothers were assigned to one of two groups: Group A (inter-
vention group: domperidone 10 mg orally three times daily
for 28 days) or Group B (comparison group: placebo 10 mg
orally three times daily for 14 days followed by domperidone
10 mg orally three times daily for 14 days). The treatment
protocol design enabled the following aims to be evaluated:
(a) an earlier introduction of domperidone compared with
later introduction, and (b) efficacy for a 2-week versus a
4-week treatment approach. The study treatment was ran-
domly assigned in a 1:1 ratio in blocks of four and eight,
stratified by center, gestational age (23–26 and 27–29 weeks
gestation at delivery), and days postdelivery (7–14 and 15–
21 days). All study personnel, point of care personnel, and
mothers were masked to the allocation.
The centers were encouraged to maintain their standard
approach in supporting the mothers as it related to duration
of pumping and the types of pumps used in their centers. For
the purpose of the trial, all mothers enrolled were encour-
aged to pump six to eight times daily for the 4-week study
period. The mothers were asked to maintain a diary provided
by the study to record pumping times, milk volumes, and any
side effects daily. Human milk volumes were verified regu-
larly by study personnel at each center. Each mother was
asked to immediately report to the study site any adverse
events experienced. Nonpharmacologic (skin-to-skin,
Kangaroo care, etc.) approaches were encouraged. Serum
prolactin levels were not measured for this study because
past studies showed an increase in prolactin levels but an
inconsistent relationship between these levels and the vol-
ume of milk produced.
Because of concerns of Q-Tc interval prolongation related
to domperidone, each mother had two electrocardiograms
(ECGs) performed during the study period: at entry and at
the end of the 4-week study medication period. Each infant
had ECGs completed at the start and end of the study period
if the mother consented to these ECGs. The ECGs, maternal
and infant, were reviewed centrally by an adult and a pediat-
ric cardiologist, respectively, at prespecified times during the
study to determine the presence of a Q-Tc interval prolonga-
tion during the 4-week study medication period.
During the 4-week study medication period, mothers
were provided two 2-week supplies of the study medica-
tion—the first at study entry, and the second prior to Day 15
of the study. Follow-up was conducted by phone or in-person
at the calculated term gestation (40 weeks postconceptual
age) and at 6 weeks corrected gestational age (6 weeks post-
term gestation). Mothers were asked questions regarding
feeding patterns, continued frequency of breast stimulation,
additional use of galactogogues or alternatives after the study
medication period, and the use of feeding supplementation
for their infant(s) at each time point. If an infant was trans-
ferred to another care facility outside of the study site before
28 days, the center was asked to remain connected with the
mother to maintain compliance with the study medication,
pumping, and diary entries and maintain follow-up at term
and at 6 weeks postterm gestation.
Measurements
The primary outcome measure was the proportion of mothers
who achieved a 50% increase in milk volume from the base-
line expressed milk volume at study entry to the end of the first
2-week period on Day 14. If human milk volumes were miss-
ing on Day 14 and/or Day 28, volumes were checked for the
preceding 2 days to determine inclusion. The secondary out-
come measures were (a) the proportion of mothers who
achieved a 50% increase in expressed milk volume on Day 28,
(b) mean milk volume on Days 14 and 28, and (c) mean per-
centage volume change from Days 0 to 14 and Days 15 to 28.
Data Analysis
The sample size for the trial was 560 mothers (280 per
group). With the trial stopping early at 90 mothers, we had
80% power to detect a 20% difference in proportions in the
two groups, anticipating that 60% of the mothers in Group B
who were receiving placebo would still be able to achieve a
50% increase in milk volume at the end of the initial 14-day
period with nonpharmacologic approaches.
No formal interim analysis was planned; safety reviews
were to be conducted by an independent Data Safety
Monitoring Board after the first 175 and 350 mothers were
randomized and enrolled into the study. At both of these
reviews, serious adverse events would be assessed and data
analyzed.
An a priori intention-to-treat analysis was conducted: all
of the mothers who were enrolled and randomized were
included and analyzed in the groups to which they were ran-
domized. The analysis was carried out using SAS Version 9.3
(SAS Institute, Cary, North Carolina, USA). Descriptive sta-
tistics were calculated for all variables of interest. Continuous
measures were summarized using means and standard devia-
tions (SDs), whereas categorical measures were summarized
using counts and percentages. Where applicable, nonpara-
metric statistics (Wilcoxon rank sum test) were used.
The primary and secondary outcomes were assessed
between groups using a logistic regression model.
Specifically, generalized estimating equations with a logit
link function were used to account for correlation among
184 Journal of Human Lactation 33(1)

Figure 1.  Trial profile.

Table 1.  Baseline Characteristics of Mothers at Study Entry. Table 2.  Outcomes on Days 14 and 28.

Characteristic Group A Group B Group A Group B OR (95% CI) p

a
Married/common law 38 (84.4) 37 (82.2) No. (%) of mothers who 35 (77.8%) 26 (57.8%) 2.56 [1.02, 6.25] .04a
achieved a 50% increase
Nulliparous 28 (62.2) 33 (73.3)
in milk volume on
Spontaneous pregnancy 43 (95.6) 37 (82.2) Day 14
Comorbidities prior to pregnancy 20 (44.4) 16 (35.6) Missing Day 14 volumes 0 5  
Comorbidities during pregnancy 28 (62.2) 18 (40.0) No. (%) of mothers who 31 (68.9%) 28 (62.2%) 1.35 [0.56, 3.22] .51
Comorbidities after delivery 5 (11.1) 9 (20.0) achieved 50% increase
Antenatal corticosteroids 41 (91.1) 35 (77.8) in milk volume on
Day 28
Note. Data are given as n (%). Group A: 4 weeks of domperidone Missing Day 28 volumes 4 7  
(N = 45). Group B: 2 weeks of placebo + 2 weeks of domperidone (N = 45).
Note. CI = confidence interval; OR = odds ratio. Group A: 4 weeks of domperidone
(N = 45). Group B: 2 weeks of placebo + 2 weeks of domperidone (N = 45).
a
This favors Group A over Group B.
observations taken at the same site as well as multiple births
by the same mother. Odds ratios (ORs) together with 95%
confidence intervals (CIs) and significance levels were Group B. Mean (SD) milk volumes at study entry were also
calculated. similar for both groups: 121 (96) ml for Group A and 115 (95)
ml for Group B. During the study medication period, 11 moth-
ers stopped pumping and taking the study medication—5 in
Results
the first 14 days and the remaining 6 in the second 14 days.
Between June 1, 2012, and June 30, 2015, 90 mothers were Table 2 shows the proportion of mothers who achieved a
enrolled at the eight participating centers and equally assigned 50% increase in expressed milk volume on Day 14 and Day
to Group A or Group B as outlined in Figure 1. Baseline char- 28, respectively. The proportion of mothers who achieved a
acteristics were similar in the two study groups (see Table 1). 50% increase on Day 14 was significantly higher in Group A
The mean maternal age for Group A was 31.3 years and for (77.8%) compared with Group B (57.8%), OR = 2.56, 95%
Group B, 33.6 years. The mean entry into the study was 14 CI [1.02, 6.25], p = .04. There was no significant difference
days (range = 10–20) for Group A and 15 days (range = 8–19) in mean (SD) milk volume on Day 14: 267 (189) ml for
for Group B. The gestational age at delivery was similar Group A compared with 217 (168) ml for Group B (p = .21),
between the two groups: 26.9 weeks for Group A and 27.3 for as shown in Table 3.
Asztalos et al. 185

Table 3.  Mean Milk Volumes on Days 14 and 28. Table 5.  Follow-Up at Term and 6 Weeks Postterm Gestation.

Group A Group B p Group A Group B

Mean (SD) milk volume 267 (189) 217 (168) .20 Follow-up term gestation  
on Day 14 (ml)   Provision of human milk 26 (57.8) 27 (60.0)
Mean (SD) milk volume 290 (211) 302 (230) .88   Supplementation to human 33 (73.3) 31 (68.9)
on Day 28 (ml) milk (formula/donor human
milk)
Note. Group A: 4 weeks of domperidone (N = 45). Group B: 2 weeks of
  Use of lactation-inducting 30 (66.7) 30 (66.7)
placebo + 2 weeks of domperidone (N = 45).
compounds post study period
Follow-up 6 weeks postterm  
Table 4.  Mean Percentage Volume Change on Days 14 and 28. gestation
  Provision of human milk 19 (42.2) 20 (44.4)
Group A Group B p   Supplementation to human 32 (71.1) 30 (66.7)
Mean (range) % 254 (–100 to 2,129) 175 (–100 to 923) .19a milk (formula)
volume change   Use of lactation-inducting 18 (40.0) 20 (44.4)
Day 0 to Day 14 compounds post study period
Mean (range) % 22 (–68 to 200) 49 (–100 to 254) .05a
volume change Note. Data are given as n (%). Group A: 4 weeks of domperidone
Day 15 to Day 28 (N = 45). Group B: 2 weeks of placebo + 2 weeks of domperidone (N = 45).

Note. Group A: 4 weeks of domperidone (N = 45). Group B: 2 weeks of placebo + 2

weeks of domperidone (N = 45). Table 6.  Maternal Adverse Events.
a
Wilcoxon rank sum test was used.
Group A Group B
At Day 28, there was no difference in the number of moth-
Maternal events  
ers who achieved a 50% increase between Group A (68.9%)   Baseline to Day 14 20 (68) 15 (65)
and Group B (62.3%), OR = 1.35, 95% CI [0.56, 3.20], p =   Day 15 to end of study 10 (32) 8 (35)
.51. There was no significant difference in mean (SD) milk Category of maternal events  
volume on Day 28: 290 (211) ml for Group A compared with  Cardiac 0 (0.0) 2 (8.7)a
302 (230) ml for Group B (p = .88), as shown in Table 3.  Gastrointestinal 3 (9.7) 9 (39.1)
Although there was no significant difference in mean  Obstetrical 3 (9.7) 1 (4.3)
milk volume on Day 28 between the two groups, the mothers   Central Nervous System: headache 10 (32.3) 3 (13.0)
in Group B did experience a significant percentage volume   Central Nervous System: other 3 (9.7) 2 (8.7)
change from Day 15 to Day 28 with the start of domperidone  Respiratory 3 (9.7) 2 (8.7)
(see Table 4).  Infection 4 (12.9) 3 (13.0)
Table 5 outlines the outcomes for the two follow-up study  Other 5 (16.1) 1 (4.3)
points in the study. Regardless of the assigned grouping,
Note. Data are given as n (%). Group A: 4 weeks of domperidone (no. of
almost 60% of the study participants attempted to continue to events = 31). Group B: 2 weeks of placebo + 2 weeks of domperidone
provide human milk and continued with some form of lacta- (no. of events = 23).
a
tion-inducing compounds at term gestation. The numbers The events included low-lying ectopic atrial rhythm (benign variant) and
dropped down to slightly more than 40% for the combined palpitations (electrocardiogram normal).
groups at 6 weeks postterm gestation.
Tables 6 and 7 outline the adverse events noted during
Discussion
the entire study period for both the mothers and the infants.
No serious adverse events were reported. It is interesting Our study focused on a high-risk group of mothers (gave
that the majority (65%–68%) of the events took place in the birth < 30 weeks gestation) with a more defined definition of
first 2 weeks irrespective of the mother being on domperi- inadequate human milk volume. We were able to demon-
done or the placebo. It is important that there was no evi- strate that (a) more mothers were able to achieve an increase
dence of prolongation of Q-Tc interval with any mother if given domperidone on or before 21 days postdelivery, (b)
participating in the trial. There was a total of 103 infants administering domperidone on or before 21 days postdeliv-
born to the 90 mothers: 52 in Group A and 51 in Group B. ery was effective in increasing human milk volume within a
Of these, 92% and 86%, respectively, had ECGs completed 2-week period but the volumes achieved were not of great
at the start of the study medication period and 75% and magnitude, and (c) mothers who had started domperidone 2
73%, respectively, at the end. From these, a total of 5 infants weeks later were still able to produce milk at a similar vol-
was found to have a Q-Tc interval > 500 ms; all of these ume to mothers who had started 2 weeks earlier.
infants were asymptomatic and no intervention was insti- The findings of increasing human milk volume are con-
tuted at the study centers. sistent with the other trials evaluating domperidone as a
186 Journal of Human Lactation 33(1)
Table 7.  Neonatal Adverse Events.
Neonatal event Group A Group B
Cardiac arrhythmia 0 (0.0) 0 (0.0)
Q-Tc interval: 442 to > 500 ms 2a 3b
Infection 6 (43.0) 8 (57.0)
Pulmonary 1 (7.0) 0 (0.0)
Gastrointestinal 2 (14.0) 3 (21.0)
Neurological 2 (14.0) 0 (0.0)
Genitourinary 1 (7.0) 0 (0.0)
Death 2 (14.0)c 3 (21.0)d
Note. Data are given as n (%). Group A: 4 weeks of domperidone (no. of
events = 14). Group B: 2 weeks of placebo + 2 weeks of domperidone
(no. of events = 14).
a
The event was present in two infants at study end electrocardiogram.
b
The event was present in three infants: two at study start and one at
study end electrocardiogram. cDeath was due to respiratory failure and
extreme prematurity, respectively. dDeath was due to sepsis in two
infants and extreme prematurity in one infant.
galactogogue (Campbell-Yeo et al., 2010; da Silva, Knoppert,
Angelini, & Forret, 2001; Ingram, Taylor, Churchill, Pike, &
Greenwood, 2012; Knoppert et al., 2013). Our study focused
on an earlier timing of introduction, within 21 days postde-
livery, to determine if this approach would be more helpful.
Even though we found that an earlier introduction was ben-
eficial, we also found that delaying treatment with domperi-
done still enabled mothers to demonstrate a response to
treatment some 22 to 35 days following delivery. Our study
was not able to demonstrate a significant measure of effec-
tiveness for a 4-week treatment approach compared with the
more studied 2 weeks. There appeared to be no more appre-
ciable gain with respect to human milk supply from a 14- to
28-day treatment course, but supply was essentially sus-
tained, which may be clinically important.
Because of the cardiac concerns that were presenting
prior to the start of this trial, we did ECGs to track any poten-
tial changes. We did not see any Q-Tc abnormalities during
the conduct of the trial. We recognize that conclusions
regarding safety along that line cannot be drawn because of
our small sample size, but we were reassured that we did not
see any effects as described in the literature (Paul et al., 2015;
Rossi & Giorgi, 2010). We did not have consistency in the
infants’ ECGs to draw any conclusions. Because of different
feeding policies in the centers, it was not always clear if an
infant had received human milk pumped during the time his
or her mother was on the study medication. There were five
neonatal ECGs with a Q-Tc interval > 500 ms in clinically
asymptomatic preterm infants, at the start and end of the
study medication period; these may be innate findings related
to the electrophysiologic mechanisms of preterm infants
requiring more evaluation (Ulrich et al., 2014).
The incidence of mothers experiencing an inadequate
milk volume and the rate of recruitment into the trial were
less than originally anticipated, despite adjustments in the
inclusion criteria early into the trial. Although this may, in
part, be due to an overestimation on our part and the part of
our collaborators, the lower incidence may also be the result
of activities initiated through a national neonatal endeavor
conducted in Canada to reduce neonatal morbidity, called
Evidence-Based Practice for Improving Quality (EPIQ;
www.epiq.ca). Many of our centers participated in EPIQ and
focused on reducing necrotizing enterocolitis as a morbidity
of interest. One strategy among the centers was to improve
the early provision of mother’s own milk by initiating lacta-
tion support immediately following delivery as well as
improving lactation support for this group of mothers.
Even though we were able to demonstrate that domperi-
done was effective, there were several concerns for both
groups of mothers. They continued to have milk volume
issues over the remaining time of hospitalization and early
postdischarge. They remained on a variety of lactation-
inducing compounds for an extended period of time. This
reaffirms that these mothers represent a subgroup of preterm
mothers who need ongoing support and encouragement to
provide human milk for their preterm infants throughout
their infants’ neonatal hospitalization and postdischarge.
Over the 3 years of the study, there were four warnings
issued by Health Canada regarding the risk of prolongation
of the Q-Tc interval and the risk of cardiac arrhythmias and
sudden death (Health Canada, 2012a, 2012b, 2015a, 2015b).
The information had a cumulative effect on recruitment and
a decision was made to stop the trial early at 16% of its tar-
geted sample size. Despite these warnings, there was never a
request from Health Canada to stop the trial. This is not the
first trial having challenges in recruitment in the face of an
unfavorable environment. The DART study also became a
victim of a climate not conducive to the study of dexametha-
sone in the management of chronic lung disease in very pre-
term infants and terminated at 9% of the projected sample
size (Doyle et al., 2006).
A strength was the rigor of the study conduct to ensure
consistency and integrity of the results. Coordinators were
encouraged to maintain contact with the mothers on a weekly
basis to ensure compliance, to ensure that the mothers
recorded milk volumes as diligently as possible, and to
ensure that adverse events were appropriately monitored.
This study was conducted as a masked trial with a modified
placebo arm, as there was concern that mothers would not
participate if they did not receive any domperidone during
the study period. Recruiting mothers in future trials involv-
ing domperidone and a placebo may be impossible; mothers
know that domperidone appears to have some benefit and
may not be willing to consider being randomized to a pla-
cebo. Finally, our aim for this article was to estimate the
effects of allocating an approach in care with domperidone in
clinical practice, that is, whether initiating treatment with
domperidone earlier would achieve a 50% increase in human
milk volume compared with initiating later. It will be impor-
tant to assess the effects of domperidone more clearly to see
which mothers truly benefited or did not benefit from this
approach in care.
Asztalos et al. 187
Conclusion
Domperidone supported more mothers to increase their milk
volume as early as 8 to 21 days postdelivery; however, the
gain in volume was modest and not significantly different.
From a clinical perspective, mothers should be carefully
assessed to ensure that an inadequate human milk supply is
present prior to considering domperidone for lactation sup-
port. Because of the current concerns for cardiac events, a
careful risk–benefit assessment is necessary.
Acknowledgments
The authors thank all of the participants in the EMPOWER Trial for
their ongoing participation and the staff at the coordinating center
for their hard work and dedication.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The authors disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article:
EMPOWER was funded by the Canadian Institutes of Health
Research (CIHR) grant MOP#114980. CIHR had no role in the
design, management, data collection, analysis, or interpretation of
the data. CIHR had no role in the writing of the manuscript or in the
decision to submit for publication.
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