NIHR DC Discover

NIHR Signal Domperidone increases breast milk production in mothers of premature babies

Published on 8 May 2018

doi: 10.3310/signal-00590

The drug domperidone increases the amount of breast milk women produce. This review looked at its use for up to two weeks in women with premature babies being fed with expressed milk. Women had a moderate increase in breast milk of about 88ml a day, a clinically important increase for these small babies.

Domperidone is an anti-sickness medication. It has not been widely used to increase breast milk because of unknown effectiveness and concerns that it can cause an irregular heart rhythm with longer-term use in older people.

This review found it can moderately increase milk production. Though no serious or cardiac side effects occurred in the studies, only 192 women participated in the trials, so rarer side effects may still occur.

Overall, the risk of irregular heart rhythms in mothers may be outweighed by the benefits of increased breast milk consumption in premature infants. Informed consent is necessary for this use of domperidone.

Share your views on the research.

Why was this study needed?

Exclusive breastfeeding for the first six months of life has benefits for both mother and baby. This includes fewer infections in babies and increased weight loss in mothers.

About eight in every 100 babies are born prematurely in England and Wales. Premature babies who are separated from their mothers for medical care may need to be fed with expressed breast milk for several weeks. Expressing breast milk may not stimulate the production of enough breast milk.

A Cochrane review in 2012 identified two studies of 59 women which suggested that the drug domperidone, usually prescribed for nausea and vomiting, might increase breast milk production. However, its use has been limited because of concerns about adverse cardiac problems in older people. This may not be the case for young otherwise healthy women. Therefore, this systematic review aimed to collate additional evidence of the safety and effectiveness of domperidone in mothers of premature babies.

What did this study do?

This systematic review identified five randomised controlled trials of domperidone compared with placebo in 192 women who were expressing breast milk. All studies used the same dose of domperidone: 10mg three times a day. One study assessed domperidone use for five days, two studies assessed seven days’ use, and two studies assessed 14 days’ use.

Most studies included women with premature babies aged one to three weeks, who were expressing milk but had low milk supply. In two studies, low milk supply was defined as less than 250ml per kg of the baby’s weight per day.

Overall, these studies were rated as good quality. The small number of women taking domperidone means that uncommon and rarer adverse effects of the drug may not have been seen.

What did it find?

  • Domperidone increased mean daily expressed milk volume by 88ml/day (95% confidence interval [CI] 57 to 112; five studies, 192 women). The amount was similar after five or 14 days of treatment and considered clinically important in this situation.
  • Separate analyses by study quality showed differences in the results. In studies rated as low risk of bias, milk production increased by 122ml/day (95% CI 75 to 169; two studies, 75 women). In studies rated as high risk of bias, milk production increased by 61ml/day (95% CI 19 to 104; three studies, 117 women).
  • Domperidone did not increase the risk of adverse events in mothers (risk ratio 1.05, 95% CI 0.65 to 1.71; five studies, 192 women). Adverse events included a headache, gastrointestinal, respiratory, and neurological symptoms such as sleep disturbance and dizziness.
  • No women withdrew from the studies because of adverse events, and no serious adverse events were reported. Only one study specifically measured effects on the mothers’ heartbeat, in which no effects were seen.
  • Two studies reported no adverse events in infants in either group. Neonatal adverse events were seen in 14 infants in both groups in one study. This study measured effects on the infants’ heartbeat (long QTc syndrome). Long QTc syndrome was seen in two babies at the start of the study and in three babies at the end of the study. They did not require any treatment. It was not clear whether the mothers of those babies had taken domperidone or placebo.

What does current guidance say on this issue?

Exclusive breastfeeding for the first six months of life is recommended internationally. NICE’s guidelines on postnatal care and maternal and child nutrition include advice on supporting women to achieve successful breastfeeding. Both of these guidelines are being updated.

A drug safety alert on domperidone in 2014 restricted its use because of irregular heart rhythms, occasionally leading to sudden death, particularly in people older than 60 years. It should be used only for short periods, usually no longer than one week.

There is no guidance or advice for using domperidone to increase milk supply in breastfeeding mothers.

What are the implications?

Domperidone can increase breast milk supply in mothers with premature infants who need to be fed with expressed breast milk. The risk of irregular heartbeats may be lower with short-term use in new mothers than was seen with regular use in people older than 60 years. The number of women studied is too low to be sure of its safety.

Domperidone does not have marketing authorisation in the UK for increasing breast milk supply. Informed consent should be obtained and documented before use, following the General Medical Council's prescribing unlicensed medicines guidance.

Citation and Funding

Grzeskowiak LE, Smithers LG, Amir LH, et al. Domperidone for increasing breast milk volume in mothers expressing breast milk for their preterm infants: a systematic review and meta-analysis. BJOG. 2018. [Epub ahead of print].

The authors were supported by the Australian National Health and Medical Research Council.

Bibliography

Donovan TJ and Buchanan K. Medications for increasing milk supply in mothers expressing breastmilk for their preterm hospitalised infants. Cochrane Database Syst Rev. 2012;3:CD005544.

EMC. Domperidone: summary of product characteristics. Surrey: Electronic Medicines Consortium; 2017.

General Medical Council. Prescribing unlicensed medicines. London: General Medical Council; accessed 2018.

Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev. 2012;8:CD003517.

Medicines and Healthcare products Regulatory Agency. Domperidone: risks of cardiac side effects. London: Medicines and Healthcare products Regulatory Agency; 2014.

NICE. Maternal and child nutrition. PH11. London: National Institute for Health and Care Excellence; 2008.

NICE. Postnatal care up to 8 weeks after birth. CG37. London: National Institute for Health and Care Excellence; 2006.

Office for National Statistics. Birth characteristics in England and Wales: 2016. London: Office for National Statistics; 2017.

World Health Organization. Breastfeeding. Geneva: World Health Organization; accessed 2018.

Why was this study needed?

Exclusive breastfeeding for the first six months of life has benefits for both mother and baby. This includes fewer infections in babies and increased weight loss in mothers.

About eight in every 100 babies are born prematurely in England and Wales. Premature babies who are separated from their mothers for medical care may need to be fed with expressed breast milk for several weeks. Expressing breast milk may not stimulate the production of enough breast milk.

A Cochrane review in 2012 identified two studies of 59 women which suggested that the drug domperidone, usually prescribed for nausea and vomiting, might increase breast milk production. However, its use has been limited because of concerns about adverse cardiac problems in older people. This may not be the case for young otherwise healthy women. Therefore, this systematic review aimed to collate additional evidence of the safety and effectiveness of domperidone in mothers of premature babies.

What did this study do?

This systematic review identified five randomised controlled trials of domperidone compared with placebo in 192 women who were expressing breast milk. All studies used the same dose of domperidone: 10mg three times a day. One study assessed domperidone use for five days, two studies assessed seven days’ use, and two studies assessed 14 days’ use.

Most studies included women with premature babies aged one to three weeks, who were expressing milk but had low milk supply. In two studies, low milk supply was defined as less than 250ml per kg of the baby’s weight per day.

Overall, these studies were rated as good quality. The small number of women taking domperidone means that uncommon and rarer adverse effects of the drug may not have been seen.

What did it find?

  • Domperidone increased mean daily expressed milk volume by 88ml/day (95% confidence interval [CI] 57 to 112; five studies, 192 women). The amount was similar after five or 14 days of treatment and considered clinically important in this situation.
  • Separate analyses by study quality showed differences in the results. In studies rated as low risk of bias, milk production increased by 122ml/day (95% CI 75 to 169; two studies, 75 women). In studies rated as high risk of bias, milk production increased by 61ml/day (95% CI 19 to 104; three studies, 117 women).
  • Domperidone did not increase the risk of adverse events in mothers (risk ratio 1.05, 95% CI 0.65 to 1.71; five studies, 192 women). Adverse events included a headache, gastrointestinal, respiratory, and neurological symptoms such as sleep disturbance and dizziness.
  • No women withdrew from the studies because of adverse events, and no serious adverse events were reported. Only one study specifically measured effects on the mothers’ heartbeat, in which no effects were seen.
  • Two studies reported no adverse events in infants in either group. Neonatal adverse events were seen in 14 infants in both groups in one study. This study measured effects on the infants’ heartbeat (long QTc syndrome). Long QTc syndrome was seen in two babies at the start of the study and in three babies at the end of the study. They did not require any treatment. It was not clear whether the mothers of those babies had taken domperidone or placebo.

What does current guidance say on this issue?

Exclusive breastfeeding for the first six months of life is recommended internationally. NICE’s guidelines on postnatal care and maternal and child nutrition include advice on supporting women to achieve successful breastfeeding. Both of these guidelines are being updated.

A drug safety alert on domperidone in 2014 restricted its use because of irregular heart rhythms, occasionally leading to sudden death, particularly in people older than 60 years. It should be used only for short periods, usually no longer than one week.

There is no guidance or advice for using domperidone to increase milk supply in breastfeeding mothers.

What are the implications?

Domperidone can increase breast milk supply in mothers with premature infants who need to be fed with expressed breast milk. The risk of irregular heartbeats may be lower with short-term use in new mothers than was seen with regular use in people older than 60 years. The number of women studied is too low to be sure of its safety.

Domperidone does not have marketing authorisation in the UK for increasing breast milk supply. Informed consent should be obtained and documented before use, following the General Medical Council's prescribing unlicensed medicines guidance.

Citation and Funding

Grzeskowiak LE, Smithers LG, Amir LH, et al. Domperidone for increasing breast milk volume in mothers expressing breast milk for their preterm infants: a systematic review and meta-analysis. BJOG. 2018. [Epub ahead of print].

The authors were supported by the Australian National Health and Medical Research Council.

Bibliography

Donovan TJ and Buchanan K. Medications for increasing milk supply in mothers expressing breastmilk for their preterm hospitalised infants. Cochrane Database Syst Rev. 2012;3:CD005544.

EMC. Domperidone: summary of product characteristics. Surrey: Electronic Medicines Consortium; 2017.

General Medical Council. Prescribing unlicensed medicines. London: General Medical Council; accessed 2018.

Kramer MS, Kakuma R. Optimal duration of exclusive breastfeeding. Cochrane Database Syst Rev. 2012;8:CD003517.

Medicines and Healthcare products Regulatory Agency. Domperidone: risks of cardiac side effects. London: Medicines and Healthcare products Regulatory Agency; 2014.

NICE. Maternal and child nutrition. PH11. London: National Institute for Health and Care Excellence; 2008.

NICE. Postnatal care up to 8 weeks after birth. CG37. London: National Institute for Health and Care Excellence; 2006.

Office for National Statistics. Birth characteristics in England and Wales: 2016. London: Office for National Statistics; 2017.

World Health Organization. Breastfeeding. Geneva: World Health Organization; accessed 2018.

Domperidone for increasing breast milk volume in mothers expressing breast milk for their preterm infants: a systematic review and meta-analysis

Published on 23 February 2018

Grzeskowiak, L. E.,Smithers, L. G.,Amir, L. H.,Grivell, R. M.

Bjog , 2018

BACKGROUND: Mothers of preterm infants often struggle to produce enough breast milk to meet the nutritional needs of their infant. Galactagogues such as domperidone are often prescribed to increase breast milk supply, but evidence supporting their role in clinical practice is uncertain. OBJECTIVE: To evaluate the efficacy and safety of domperidone for increasing breast milk volume in mothers expressing breast milk for their preterm infants. SEARCH STRATEGY: Medline, Embase, and Web of Science were searched without language restrictions, from first publication until January 2017. Bibliographies of articles and reviews were hand searched for additional reports. SELECTION CRITERIA: Randomised controlled trials that compared domperidone with placebo in mothers of preterm infants (<37 weeks' gestation) experiencing insufficient milk supply. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and evaluated study quality. Difference in breast milk volume, and adverse events, were combined using fixed effects meta-analysis. MAIN RESULTS: The pooled analysis of five trials consisting of 194 women demonstrated a moderate increase in daily breast milk volume of 88.3 mL/day (95% CI 56.8-119.8) with the use of domperidone compared with placebo. No difference was evident with respect to maternal adverse events (OR 1.05; 95%CI 0.65-1.71), with no reported cases of prolonged QTc syndrome or sudden cardiac death. Sensitivity analyses showed no important differences in the estimates of effects. CONCLUSIONS: Domperidone is well tolerated and results in a moderate short-term increase in expressed breast milk volume among mothers of preterm infants previously identified as having insufficient breast milk supply. This article is protected by copyright. All rights reserved.

Expert commentary

Globally, more than one in 10 pregnancies will end in preterm birth, 15 million babies per year. Preterm birth complications caused approximately one million deaths in 2015.

Breast milk has been proven to prevent infections in preterm babies and can drastically reduce this number, though lactation can be very challenging for hospitalised mothers for many reasons, included being stressed and fearful for their baby.

Healthy mothers have now a real option to increase their milk supply with a medication that is safe for them and could help them in giving their babies the best beginning in life.

Miss Mariacristina Ricci, Midwife, Birmingham Women and Children's Hospital