The benefits of breastfeeding are well recognized for both the mother and baby; thus, efforts should be made to promote initiation, duration, and exclusivity of breastfeeding [1
]. The recently published survey of Canadian women who gave birth and were residing with their infants at the time of the interview has found that breastfeeding intention and initiating rates were fairly high, 90% and 90.3%, respectively, among women of this representative sample [2
]. However, reported exclusive breastfeeding rates at three and six months fell substantially—51.7% and 14.4%. While factors that affect breastfeeding success are multiple and nonmodifiable at times, the early recognition and timely management of modifiable risk factors is warranted to improve lactation performance [3
]. Various nonpharmacological interventions have been shown to be effective and hence are incorporated in the current clinical recommendations for promoting breastfeeding [1
]. Among them are individual and group breastfeeding education provided by lactation specialists, peer counseling, in-person, or telephone support. Pharmacological interventions to improve lactation, mainly dopamine antagonists, are usually recommended only after nonpharmacological modalities have failed, and this is largely due to scarcity of available evidence and potential safety issues with pharmaceutical galactagogues [4
Domperidone, a peripheral dopamine receptor antagonist, is believed to enhance breast milk production by increasing prolactin secretion [6
]. It has a favorable safety profile when compared to metoclopramide, another dopamine receptor antagonist, with only rare extra-pyramidal side effects owing likely to poor blood-brain barrier penetration of domperidone [9
]. The drug is well tolerated with relatively few side effects reported including headache, dry mouth, and abdominal cramps [10
]. While domperidone is not available for any indication in the United States due to arrhythmia concerns, it is approved in Canada and other countries as a prokinetic agent. Moreover, there is a worldwide experience with domperidone in treating nausea and vomiting. The use of domperidone as a galactagogue, hence, represents an “off-label” indication.
In 2004, the United States Food and Drug Administration (FDA) issued an advisory against the use of domperidone as a milk enhancer due to safety concerns [13
]. There have been a few reports of cardiac arrhythmia and sudden death in cancer patients treated with intravenous domperidone which are often cited in the literature [14
]. Rapid intravenous administration or high doses of domperidone as well as concurrent hypokalemia might be significant contributors to these adverse outcomes leading to discontinuation of the intravenous route of administration. A single case report of reversible QT prolongation associated with oral domperidone administration has been published [15
]. In neonates, oral administration of domperidone was associated with QT prolongation [16
]. Whereas the potential pro-arrhythmic effect of domperidone should not be ignored, the FDA concern over the use of domperidone for promoting lactation has been regarded by lactation experts as a gross overestimation. Available pharmacokinetic data, although limited, indicates minimal excretion of domperidone into breast milk with extremely low (less than 0.01% of the maternal weight-adjusted dose) infant exposure via breast milk [6
]. No side effects have been reported in exposed infants. The American Academy of Pediatrics lists domperidone as compatible with breastfeeding [17
Nevertheless, there is a controversy regarding the role of domperidone as a galactagogue: some authors claim no or little effectiveness, largely due to limitations of available data [18
] while other researchers suggested that domperidone is a galactagogue of choice based on evidence available [4
]. This situation might be a source of confusion in the medical community and, therefore, may compromise clinical management decisions.
The objective of our study was to perform a systematic review and meta-analysis of the available data assessing the effect of domperidone on breast milk supply in women experiencing insufficient breast milk production.