557175
research-article2014
JHLXXX10.1177/0890334414557175Journal of Human LactationGrzeskowiak et al
Original Research: Brief Report
Factors Associated with Domperidone Use as a Galactogogue at an Australian Tertiary Teaching Hospital
Journal of Human Lactation 1–5 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0890334414557175 jhl.sagepub.com
Luke E. Grzeskowiak, PhD1, Julia A. Dalton, RN, RM1, and Andrea L. Fielder, PhD2
Abstract Background: Insufficient milk supply is 1 of the most commonly reported reasons for discontinuation of infant breastfeeding. Although domperidone is often used to improve milk supply, knowledge of factors associated with the use of domperidone in clinical practice is scarce. Objective: This study aimed to examine factors associated with the use of domperidone as a galactogogue at the Women’s and Children’s Hospital (WCH), Adelaide. Methods: A retrospective cohort study was conducted, involving women who delivered live-born singletons (N = 21 914) at the WCH between January 2004 and December 2008. Women dispensed domperidone were identified using WCH pharmacy dispensing records. Maternal and infant clinical data were obtained from the WCH Perinatal Statistics Collection. Relationships between maternal/infant demographic and clinical variables and the use of domperidone were examined through univariate and multivariate logistic regression analyses. Results: Key factors associated with an increased likelihood of women receiving domperidone were increasing maternal age (adjusted odds ratio [aOR] = 1.04; 95% confidence interval [CI], 1.03-1.06), maternal obesity (aOR = 1.41; 95% CI, 1.161.77), primiparity (aOR = 1.94; 95% CI, 1.63-2.30), delivery by cesarean section (aOR = 1.31; 95% CI, 1.10-1.55), preterm birth (aOR = 3.54; 95% CI, 2.79-4.50), and neonatal hospitalization (aOR = 2.51; 95% CI, 2.01-3.14). In addition, statistically significant trends were observed between increasing socioeconomic status and year of delivery and an increased likelihood of women receiving domperidone (all Ps < .004). Conclusion: These findings are of clinical importance as they not only reinforce previous findings regarding risk factors for women experiencing lactation difficulties but also highlight the need for improved research regarding the rational and efficacious use of domperidone to improve breastfeeding outcomes. Keywords breastfeeding, breastfeeding difficulties, domperidone, epidemiology, galactogogue, observational study
Well Established
Background
Despite the widespread use of domperidone as a pharmacological alternative in the clinical management of insufficient milk supply, knowledge of factors associated with its use in clinical practice remains uncertain.
Exclusive breastfeeding for the first 6 months of life is well recognized as the optimal form of nutrition to support the growth and development of term and preterm infants.1,2 One of the most commonly reported reasons for the discontinuation of infant breastfeeding is insufficient milk supply.3,4
Newly Expressed Factors associated with an increased likelihood of women receiving domperidone were increasing maternal age, higher socioeconomic status, maternal obesity, primiparity, year of delivery, delivery by cesarean section, preterm birth, and neonatal hospitalization. Identification of such factors is important in reinforcing knowledge of women at risk of experiencing lactation difficulties and in highlighting the need for improved research supporting the rational and efficacious use of domperidone to improve breastfeeding outcomes.
1
The Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia 2 School of Nursing and Midwifery, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia Date submitted: February 27, 2014; Date accepted: October 2, 2014. Corresponding Author: Luke E. Grzeskowiak, PhD, The Robinson Research Institute, The University of Adelaide, Lyell McEwin Hospital, Haydown Road, Elizabeth Vale, 5112, South Australia, Australia. Email: [email protected]
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2
Journal of Human Lactation
Following the provision of adequate education regarding breastfeeding and an appropriate trial of nonpharmacological strategies to address insufficient milk supply, evidence supports pharmacological intervention with galactogogues used to augment lactation.5 The most widely studied and commonly used galactogogues include dopamine receptor antagonists, metoclopramide and domperidone, which have both been demonstrated to be effective treatments for improving milk supply.6-10 In Australia and a number of other countries, domperidone is used “off-label” in preference to metoclopramide, as it does not cross the blood-brain barrier and is associated with fewer central nervous system side effects (ie, fatigue, irritability, depression).4,6,11 Despite its frequent use, knowledge of how domperidone is actually prescribed in clinical practice and knowledge of factors associated with its use are scarce. Therefore, the aim of this study was to examine factors associated with the use of domperidone as a galactogogue at a major tertiary teaching hospital over a 5-year period.
Methods This project was approved by the Women’s and Children’s Health Network Human Research Ethics Committee. This was a retrospective cohort study based on all deliveries occurring at the Women’s and Children’s Hospital (WCH) in the Women’s and Children’s Health Network in South Australia between January 2004 and December 2008. The WCH is a Baby-Friendly Hospital Initiative accredited hospital, with a dedicated lactation support service. A total of 23 275 pregnancies were identified during the study period. Women who were eligible for the current analysis were those who gave birth to live-born singletons (N = 21 914). Data relating to women dispensed domperidone were obtained from the WCH pharmacy dispensing records.12 Domperidone is able to be prescribed only by medical doctors, with no restrictions according to level of experience (eg, interns, registrars, and consultants are all eligible to prescribe). Guidelines regarding the use of domperidone or management of low milk supply during this time period have remained consistent, recommending domperidone as the first-line pharmacological treatment. Demographic and clinical data were obtained from the Perinatal Statistics Collection, which includes electronic data on the pregnancy and outcome of every live birth and late fetal death occurring at the hospital.13,14 The information in the Perinatal Statistics Collection has been previously validated and is reliable when compared with hospital case records.15 These data have been previously utilized to undertake a clinical audit of domperidone use at the WCH.14 A variety of maternal and infant factors known or suspected to be associated with low milk supply, which could lead to the need for domperidone, were investigated.4,16,17
These included maternal age, maternal body mass index (BMI), socioeconomic status, smoking status, race, parity, mental health illness, pre-existing and pregnancy-induced diabetes/hypertension, year of delivery, delivery by cesarean section, preterm birth, and neonate admitted to neonatal intensive care unit (NICU) or special care nursery (SCN). Smoking status was based on maternal self-report at the first antenatal visit, with smokers stratified into 3 groups according to how many cigarettes they smoked each day (1-9, 10-19, or ≥ 20). Preterm birth was defined as birth < 37 completed weeks’ gestation. Socioeconomic status for each woman was determined according to her level of advantage or relative disadvantage, based on her residential postcode and data from the Socio-Economic Indexes for Areas (SEIFA). SEIFA scores were converted to quintiles, representing widely used measures of relative socioeconomic status.18 Maternal BMI (kg/m2) was calculated using height and weight recorded during the first antenatal booking visit and subsequently classified into underweight (< 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight 25.0-29.9 kg/m2), and obese (≥ 30 kg/m2). The presence of a mental health condition (eg, depression, anxiety, schizophrenia) during pregnancy was based on data routinely collected by midwives during antenatal visits and includes conditions for which women received nonpharmacological (ie, psychological/psychiatric) and/or pharmacological (ie, medications) treatment. Associations between selected factors and domperidone use were evaluated through univariate and multivariate logistic regression analysis, generating odds ratios (ORs) and associated 95% confidence intervals (CIs). All of the covariates were included in the multivariate logistic regression model. Statistical analyses were performed using Stata IC 11.0 (Stata, College Station, TX, USA). Statistical significance was defined as a 2-sided P value of < .05.
Results Of the 21 914 women included in the study, 1100 (5%) received a dispensing for domperidone. Maternal and infant characteristics associated with receiving a dispensing for domperidone are presented in Table 1. In univariate analyses, factors associated with an increased likelihood of women receiving domperidone included increasing maternal age, increasing maternal BMI, higher socioeconomic status, Caucasian ethnicity, primiparity, presence of a mental health condition during pregnancy, pre-existing or pregnancyinduced diabetes or hypertension, increasing year of delivery, delivery by cesarean section, preterm birth, and neonatal hospitalization (Table 1). In multivariate analysis, key factors associated with an increased likelihood of women receiving domperidone were increasing maternal age (aOR = 1.04; 95% CI, 1.03-1.06), maternal obesity (aOR = 1.41; 95% CI, 1.16-1.77), primiparity (aOR = 1.94; 95% CI, 1.632.30), delivery by cesarean section (aOR = 1.31; 95% CI,
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3
Grzeskowiak et al Table 1. Factors Associated with Likelihood of Women Being Dispensed Domperidone according to Univariate and Multivariate Logistic Regression Analysis. Dispensed Domperidone, No. (%) Maternal age Maternal BMI (kg/m2) Underweight (< 18.5) Normal weight (≥ 18.5 to < 25) Overweight (≥ 25 to < 30) Obese (≥ 30) Socioeconomic status 1 (lowest) 2 3 4 5 (highest) Race Caucasian Aboriginal/TSI Asian Other Smoking status Nonsmoker 1-9 10-19 20+ Parity Multiparous Primiparous Mental health conditione Diabetes (pre-existing or gestational) Hypertension (pre-existing or gestational) Year of delivery 2004 2005 2006 2007 2008 Delivery by cesarean section Preterm birth (< 37 weeks’ gestation) Neonate admitted to NICU/SCN
No
Univariate OR (95% CI)
Multivariate OR (95% CI)a,b
P Value for Trendc
30.3 (6.1)
29.2 (5.8)d
1.03 (1.02-1.04)
1.04 (1.03-1.06)
19 (2.7) 327 (46.8) 165 (23.6) 188 (26.9)
532 (3.6) 7794 (52.4) 3738 (25.1) 2808 (18.9)
0.78 (0.59-1.04) Reference 1.01 (0.83-1.22) 1.58 (1.32-1.90)
0.75 (0.55-1.03) Reference 1.00 (0.81-1.25) 1.41 (1.13-1.77)
214 (19.5) 216 (19.7) 217 (19.8) 203 (18.5) 249 (22.7)
4862 (23.4) 4116 (19.8) 3925 (18.9) 4066 (19.6) 3792 (18.3)
Reference 1.19 (0.98-1.45) 1.26 (1.04-1.52) 1.13 (0.93-1.38) 1.49 (1.24-1.80)
Reference 1.21 (0.93-1.56) 1.43 (1.11-1.84) 1.25 (0.96-1.63) 1.39 (1.07-1.82)
899 (81.7) 27 (2.5) 126 (11.5) 48 (4.4)
15 795 (75.9) 796 (3.8) 2695 (13.0) 1528 (7.3)
Reference 0.60 (0.40-0.88) 0.82 (0.68-1.00) 0.55 (0.41-0.74)
Reference 0.72 (0.40-1.30) 0.98 (0.76-1.26) 0.78 (0.54-1.12)
828 (82.7) 79 (7.9) 75 (7.5) 19 (1.9)
16 051 (82.8) 1580 (8.2) 1312 (6.8) 432 (2.2)
Reference 0.96 (0.77-1.23) 1.11 (0.87-1.41) 0.85 (0.54-1.36)
Reference 0.96 (0.71-1.30) 1.03 (0.75-1.43) 0.81 (0.44-1.49)
459 (41.9) 636 (58.1) 97 (8.8) 96 (8.7)
11 707 (56.3) 9080 (43.7) 1290 (6.2) 1404 (6.8)
Reference 1.79 (1.58-2.02) 1.41 (1.14-1.74) 1.32 (1.06-1.64)
Reference 1.94 (1.63-2.30) 1.17 (0.87-1.58) 0.96 (0.71-1.29)
NA .001 .016 NA .628 NA NA NA
Yes
31 (2.8)
267 (1.3)
2.23 (1.53-3.25)
0.92 (0.53-1.60)
170 (15.5) 186 (16.9) 205 (18.6) 287 (26.1) 252 (22.9) 482 (43.8) 452 (41.1)
3687 (17.7) 4071 (19.6) 4125 (19.8) 4389 (21.1) 4542 (21.8) 5655 (27.2) 1873 (9.0)
Reference 0.99 (0.80-1.23) 1.08 (0.88-1.33) 1.42 (1.17-1.72) 1.20 (0.99-1.47) 2.10 (1.85-2.36) 7.05 (6.20-8.03)
Reference 0.94 (0.70-1.26) 1.12 (0.84-1.48) 1.55 (1.19-2.01) 1.25 (0.95-1.63) 1.31 (1.10-1.55) 3.54 (2.79-4.50)
.004 NA NA
565 (51.4)
3448 (16.6)
5.32 (4.70-6.02)
2.51 (2.01-3.14)
NA
Abbreviations: BMI, body mass index; CI, confidence interval; NA, not applicable; NICU, neonatal intensive care unit; OR, odds ratio; SCN, special care nursery; TSI, Torres Strait Islander. a Includes adjustment for each of the variables listed in the table. b Hosmer and Lemeshow’s goodness-of-fit test; P value = .1515 (indicates that the model fits the data well). c The P value for trend tested for a linear relation of ordinal variables using logistic regression analysis, assuming equally spaced categories. d Mean (standard deviation). e Includes mental health conditions for which women received nonpharmacological (ie, psychological/psychiatric) and/or pharmacological (ie, medications) treatment during pregnancy (eg, depression, anxiety, schizophrenia).
1.10-1.55), preterm birth (aOR = 3.54; 95% CI, 2.79-4.50), and neonatal hospitalization (aOR = 2.51; 95% CI,
2.01-3.14) (Table 1). In addition, statistically significant trends were observed between increasing socioeconomic
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4
Journal of Human Lactation
Figure 1. Percentage of Mothers Dispensed Domperidone according to Number of Weeks’ Gestation at Delivery.
status and year of delivery and an increased likelihood of women receiving domperidone (all Ps < .004). Preterm birth appeared the strongest predictor of domperidone use, with a significant linear relationship between decreasing gestational age at delivery and increasing percentage of mothers receiving domperidone (P < .001) (Figure 1).
Discussion Despite the widespread use of domperidone in many countries around the world, this is the first study to evaluate maternal and infant characteristics associated with its use. Factors associated with an increased likelihood of women receiving domperidone were increasing maternal age, higher socioeconomic status, maternal obesity, primiparity, year of delivery, delivery by cesarean section, preterm birth, and neonatal hospitalization. Although it is clear that domperidone should not be used as a substitute for, or as an alternative to, effective nonpharmacological breastfeeding support and encouragement,4 these findings are of clinical importance as they reinforce previous findings regarding risk factors for lactation difficulties and highlight the need for improved research regarding nonpharmacological and pharmacological interventions targeting high-risk women to improve breastfeeding outcomes. It is somewhat unsurprising that preterm birth and neonatal hospitalization remained the strongest factor associated with receiving domperidone in the multivariate analysis. It has been previously described that mothers who deliver infants who are unwell and require supportive care following delivery, such as preterm infants, are particularly vulnerable to difficulties breastfeeding.4,19 In many cases, these mothers are not able to breastfeed directly, which, in addition to the stressful situation of having an unwell infant, can have a detrimental effect on milk supply. Despite mothers of preterm infants being more likely to be prescribed domperidone than mothers of term infants,
greater than 50% of domperidone use was identified among mothers who delivered term infants who were not admitted to the NICU or SCN.14 Such high use among mothers of term infants represents an important evidence gap, as the vast majority of studies evaluating the use of domperidone have involved mothers of preterm infants only.7,9,10,19,20 Whether the findings from these studies are generalizable to mothers of term infants remains to be determined, as pharmacological needs and response could vary. It is possible that primiparous women were more likely to receive domperidone due to perceived compared to actual milk insufficiency, as can occur due to unfamiliarity with breastfeeding.4 Primiparous women may be unaware of normal postpartum physical breast changes, such as the softening of the breasts around 10 to 14 days postpartum, or misinterpret infant symptoms such as irritability, crying, and frequent feeding as a lack of breast milk quality or quantity.4 Furthermore, primiparous women, in addition to those with new or pre-existing mental health illness, may lack breastfeeding self-efficacy.21 Breastfeeding self-efficacy is influenced by numerous factors including prior breastfeeding experience, support from family and friends, and understanding of lactation physiology.4,21 If this were the case, however, one could expect these to be addressed through nonpharmacological strategies, such as education in correct infant positioning and attachment at the breast, increasing frequency of breastfeeds, and mechanical expression, rather than the use of domperidone.4 Previous studies have identified that maternal obesity may be associated with a delay in the onset of lactation, as well as a reduction in initiation of breastfeeding.22 A delay in onset of lactation could be perceived as milk insufficiency, which may explain the increased likelihood of domperidone use among these women. A notable finding was the statistically significant increasing trend of domperidone use according to year of delivery. This finding remained statistically significant even after controlling for other key factors such as preterm birth and neonatal hospitalization. It is possible that this suggests an increased prescribing of domperidone in line with a change in clinical practice/management of women experiencing lactation difficulties, rather than a change in maternal/infant risk factors alone. A limitation of this study is the reliance on hospital pharmacy dispensing data to identify domperidone use. This is likely an underestimate of the total number of women who received domperidone, as some may have been prescribed domperidone outside of the hospital. The identification of such use in the community setting would be of particular interest. Second, no data were available on whether women saw a lactation consultant. Data from a previous study undertaken at the same hospital, however, identified that 40% of the mothers who received domperidone were admitted to a breastfeeding unit and/or received specialist advice from a lactation consultant.14 It is important to note that the aim of this study was not to evaluate the appropriateness of domperidone use.
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Grzeskowiak et al
Conclusion This study provides a significant contribution to the literature by looking beyond factors that are associated with breastfeeding itself, but rather at factors essentially associated with lactation difficulties, of which domperidone use can be used as a marker. Future research is required to explore why particular subgroups of women are at risk of experiencing lactation difficulties and are more likely to require treatment with domperidone. Furthermore, given the widespread use of domperidone, additional evidence is required regarding the safety and efficacy (dose, duration of treatment, time to initiate domperidone) to support the development of evidence-based guidelines.12 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: The authors wish to acknowledge salary support through a National Health and Medical Research Council Australian Public Health Fellowship (ID 1070421 to LEG).
References 1. Gartner LM, Eidelman AI. Breastfeeding and the use of human milk. Pediatrics. 2005;115(2):496-506. 2. Chandran L, Gelfer P. Breastfeeding: the essential principles. Pediatr Rev. 2006;27(11):409-417. 3. Australian Health Ministers’ Conference. The Australian National Breastfeeding Strategy 2010-2015. Canberra: Australian Government Department of Health and Ageing; 2009. 4. Amir LH. Breastfeeding: managing ‘supply’ difficulties. Aust Fam Physician. 2006;35(9):686-689. 5. Donovan T, Buchanan K. Medications for increasing milk supply in mothers expressing breastmilk for their preterm hospitalised infants. Cochrane Database Syst Rev. 2012;3:CD005544. doi:10.1002/14651858.CD005544.pub2. 6. Zuppa AA, Sindico P, Orchi C, et al. Safety and efficacy of galactogogues: substances that induce, maintain and increase breast milk production. J Pharm Pharm Sci. 2010;13(2):162-174. 7. Campbell-Yeo ML, Allen AC, Joseph K, et al. Effect of domperidone on the composition of preterm human breast milk. Pediatrics. 2010;125(1):e107-e114.
8. Osadchy A, Moretti ME, Koren G. Effect of domperidone on insufficient lactation in puerperal women: a systematic review and meta-analysis of randomized controlled trials. Obstet Gynecol Int. 2012;2012. 9. da Silva OP, Knoppert DC, Angelini MM, Forret PA. Effect of domperidone on milk production in mothers of premature newborns: a randomized, double-blind, placebo-controlled trial. Can Med Assoc J. 2001;164(1):17-21. 10. Ingram J, Taylor H, Churchill C, Pike A, Greenwood R. Metoclopramide or domperidone for increasing maternal breast milk output: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2012;97(4):F241-F245. 11. Henderson A. Domperidone. Discovering new choices for lactating mothers. AWHONN Lifelines. 2003;7(1):54-60. 12. Grzeskowiak L, Gilbert A, Morrison J. Hospital pharmacy dispensing records for pharmacoepidemiology research into late gestation exposure to antidepressants. J Pharm Pract Res. 2010;40(4):265-268. 13. Grzeskowiak LE, Gilbert AL, Morrison JL. Neonatal outcomes following late gestation exposure to selective serotonin reuptake inhibitors. J Clin Psychopharmacol. 2012;32(5):615-621. 14. Grzeskowiak LE, Lim SW, Thomas AE, Ritchie U, Gordon AL. Audit of domperidone use as a galactogogue at an Australian tertiary teaching hospital. J Hum Lact. 2013;29(1):32-37. 15. McLean A, Scott J, Keane R, Sage L, Chan A. Validation of the 1994 South Australian Perinatal Data Collection Form. Adelaide, South Australia: Pregnancy Outcome Unit, Epidemiology Branch, Dept of Human Services; 2001. 16. Scott JA, Binns CW, Oddy WH. Predictors of delayed onset of lactation. Matern Child Nutr. 2007;3(3):186-193. 17. Hill PD, Aldag JC, Chatterton RT, Zinaman M. Primary and secondary mediators’ influence on milk output in lactating mothers of preterm and term infants. J Hum Lact. 2005;21(2):138-150. 18. Pearlstein T, Howard M, Salisbury A, Zlotnick C. Postpartum depression. Am J Obstet Gynecol. 2009;200(4):357-364. 19. Wan EW, Davey K, Page-Sharp M, Hartmann PE, Simmer K, Ilett KF. Dose-effect study of domperidone as a galactagogue in preterm mothers with insufficient milk supply, and its transfer into milk. Br J Clin Pharmacol. 2008;66(2):283-289. 20. Knoppert DC, Page A, Warren J, et al. The effect of two different domperidone doses on maternal milk production. J Hum Lact. 2013;29(1):38-44. 21. Dennis CL, Faux S. Development and psychometric testing of the Breastfeeding Self-Efficacy Scale. Res Nurs Health. 1999;22(5):399-409. 22. Donath S, Amir L. Does maternal obesity adversely affect breastfeeding initiation and duration? J Paediatr Child Health. 2000;36(5):482-486.
Downloaded from jhl.sagepub.com at CMU Libraries - library.cmich.edu on September 18, 2015
research-article2014
JHLXXX10.1177/0890334414557175Journal of Human LactationGrzeskowiak et al
Original Research: Brief Report
Factors Associated with Domperidone Use as a Galactogogue at an Australian Tertiary Teaching Hospital
Journal of Human Lactation 1–5 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/0890334414557175 jhl.sagepub.com
Luke E. Grzeskowiak, PhD1, Julia A. Dalton, RN, RM1, and Andrea L. Fielder, PhD2
Abstract Background: Insufficient milk supply is 1 of the most commonly reported reasons for discontinuation of infant breastfeeding. Although domperidone is often used to improve milk supply, knowledge of factors associated with the use of domperidone in clinical practice is scarce. Objective: This study aimed to examine factors associated with the use of domperidone as a galactogogue at the Women’s and Children’s Hospital (WCH), Adelaide. Methods: A retrospective cohort study was conducted, involving women who delivered live-born singletons (N = 21 914) at the WCH between January 2004 and December 2008. Women dispensed domperidone were identified using WCH pharmacy dispensing records. Maternal and infant clinical data were obtained from the WCH Perinatal Statistics Collection. Relationships between maternal/infant demographic and clinical variables and the use of domperidone were examined through univariate and multivariate logistic regression analyses. Results: Key factors associated with an increased likelihood of women receiving domperidone were increasing maternal age (adjusted odds ratio [aOR] = 1.04; 95% confidence interval [CI], 1.03-1.06), maternal obesity (aOR = 1.41; 95% CI, 1.161.77), primiparity (aOR = 1.94; 95% CI, 1.63-2.30), delivery by cesarean section (aOR = 1.31; 95% CI, 1.10-1.55), preterm birth (aOR = 3.54; 95% CI, 2.79-4.50), and neonatal hospitalization (aOR = 2.51; 95% CI, 2.01-3.14). In addition, statistically significant trends were observed between increasing socioeconomic status and year of delivery and an increased likelihood of women receiving domperidone (all Ps < .004). Conclusion: These findings are of clinical importance as they not only reinforce previous findings regarding risk factors for women experiencing lactation difficulties but also highlight the need for improved research regarding the rational and efficacious use of domperidone to improve breastfeeding outcomes. Keywords breastfeeding, breastfeeding difficulties, domperidone, epidemiology, galactogogue, observational study
Well Established
Background
Despite the widespread use of domperidone as a pharmacological alternative in the clinical management of insufficient milk supply, knowledge of factors associated with its use in clinical practice remains uncertain.
Exclusive breastfeeding for the first 6 months of life is well recognized as the optimal form of nutrition to support the growth and development of term and preterm infants.1,2 One of the most commonly reported reasons for the discontinuation of infant breastfeeding is insufficient milk supply.3,4
Newly Expressed Factors associated with an increased likelihood of women receiving domperidone were increasing maternal age, higher socioeconomic status, maternal obesity, primiparity, year of delivery, delivery by cesarean section, preterm birth, and neonatal hospitalization. Identification of such factors is important in reinforcing knowledge of women at risk of experiencing lactation difficulties and in highlighting the need for improved research supporting the rational and efficacious use of domperidone to improve breastfeeding outcomes.
1
The Robinson Research Institute, The University of Adelaide, Adelaide, South Australia, Australia 2 School of Nursing and Midwifery, Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia Date submitted: February 27, 2014; Date accepted: October 2, 2014. Corresponding Author: Luke E. Grzeskowiak, PhD, The Robinson Research Institute, The University of Adelaide, Lyell McEwin Hospital, Haydown Road, Elizabeth Vale, 5112, South Australia, Australia. Email: [email protected]
Downloaded from jhl.sagepub.com at CMU Libraries - library.cmich.edu on September 18, 2015
2
Journal of Human Lactation
Following the provision of adequate education regarding breastfeeding and an appropriate trial of nonpharmacological strategies to address insufficient milk supply, evidence supports pharmacological intervention with galactogogues used to augment lactation.5 The most widely studied and commonly used galactogogues include dopamine receptor antagonists, metoclopramide and domperidone, which have both been demonstrated to be effective treatments for improving milk supply.6-10 In Australia and a number of other countries, domperidone is used “off-label” in preference to metoclopramide, as it does not cross the blood-brain barrier and is associated with fewer central nervous system side effects (ie, fatigue, irritability, depression).4,6,11 Despite its frequent use, knowledge of how domperidone is actually prescribed in clinical practice and knowledge of factors associated with its use are scarce. Therefore, the aim of this study was to examine factors associated with the use of domperidone as a galactogogue at a major tertiary teaching hospital over a 5-year period.
Methods This project was approved by the Women’s and Children’s Health Network Human Research Ethics Committee. This was a retrospective cohort study based on all deliveries occurring at the Women’s and Children’s Hospital (WCH) in the Women’s and Children’s Health Network in South Australia between January 2004 and December 2008. The WCH is a Baby-Friendly Hospital Initiative accredited hospital, with a dedicated lactation support service. A total of 23 275 pregnancies were identified during the study period. Women who were eligible for the current analysis were those who gave birth to live-born singletons (N = 21 914). Data relating to women dispensed domperidone were obtained from the WCH pharmacy dispensing records.12 Domperidone is able to be prescribed only by medical doctors, with no restrictions according to level of experience (eg, interns, registrars, and consultants are all eligible to prescribe). Guidelines regarding the use of domperidone or management of low milk supply during this time period have remained consistent, recommending domperidone as the first-line pharmacological treatment. Demographic and clinical data were obtained from the Perinatal Statistics Collection, which includes electronic data on the pregnancy and outcome of every live birth and late fetal death occurring at the hospital.13,14 The information in the Perinatal Statistics Collection has been previously validated and is reliable when compared with hospital case records.15 These data have been previously utilized to undertake a clinical audit of domperidone use at the WCH.14 A variety of maternal and infant factors known or suspected to be associated with low milk supply, which could lead to the need for domperidone, were investigated.4,16,17
These included maternal age, maternal body mass index (BMI), socioeconomic status, smoking status, race, parity, mental health illness, pre-existing and pregnancy-induced diabetes/hypertension, year of delivery, delivery by cesarean section, preterm birth, and neonate admitted to neonatal intensive care unit (NICU) or special care nursery (SCN). Smoking status was based on maternal self-report at the first antenatal visit, with smokers stratified into 3 groups according to how many cigarettes they smoked each day (1-9, 10-19, or ≥ 20). Preterm birth was defined as birth < 37 completed weeks’ gestation. Socioeconomic status for each woman was determined according to her level of advantage or relative disadvantage, based on her residential postcode and data from the Socio-Economic Indexes for Areas (SEIFA). SEIFA scores were converted to quintiles, representing widely used measures of relative socioeconomic status.18 Maternal BMI (kg/m2) was calculated using height and weight recorded during the first antenatal booking visit and subsequently classified into underweight (< 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight 25.0-29.9 kg/m2), and obese (≥ 30 kg/m2). The presence of a mental health condition (eg, depression, anxiety, schizophrenia) during pregnancy was based on data routinely collected by midwives during antenatal visits and includes conditions for which women received nonpharmacological (ie, psychological/psychiatric) and/or pharmacological (ie, medications) treatment. Associations between selected factors and domperidone use were evaluated through univariate and multivariate logistic regression analysis, generating odds ratios (ORs) and associated 95% confidence intervals (CIs). All of the covariates were included in the multivariate logistic regression model. Statistical analyses were performed using Stata IC 11.0 (Stata, College Station, TX, USA). Statistical significance was defined as a 2-sided P value of < .05.
Results Of the 21 914 women included in the study, 1100 (5%) received a dispensing for domperidone. Maternal and infant characteristics associated with receiving a dispensing for domperidone are presented in Table 1. In univariate analyses, factors associated with an increased likelihood of women receiving domperidone included increasing maternal age, increasing maternal BMI, higher socioeconomic status, Caucasian ethnicity, primiparity, presence of a mental health condition during pregnancy, pre-existing or pregnancyinduced diabetes or hypertension, increasing year of delivery, delivery by cesarean section, preterm birth, and neonatal hospitalization (Table 1). In multivariate analysis, key factors associated with an increased likelihood of women receiving domperidone were increasing maternal age (aOR = 1.04; 95% CI, 1.03-1.06), maternal obesity (aOR = 1.41; 95% CI, 1.16-1.77), primiparity (aOR = 1.94; 95% CI, 1.632.30), delivery by cesarean section (aOR = 1.31; 95% CI,
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Grzeskowiak et al Table 1. Factors Associated with Likelihood of Women Being Dispensed Domperidone according to Univariate and Multivariate Logistic Regression Analysis. Dispensed Domperidone, No. (%) Maternal age Maternal BMI (kg/m2) Underweight (< 18.5) Normal weight (≥ 18.5 to < 25) Overweight (≥ 25 to < 30) Obese (≥ 30) Socioeconomic status 1 (lowest) 2 3 4 5 (highest) Race Caucasian Aboriginal/TSI Asian Other Smoking status Nonsmoker 1-9 10-19 20+ Parity Multiparous Primiparous Mental health conditione Diabetes (pre-existing or gestational) Hypertension (pre-existing or gestational) Year of delivery 2004 2005 2006 2007 2008 Delivery by cesarean section Preterm birth (< 37 weeks’ gestation) Neonate admitted to NICU/SCN
No
Univariate OR (95% CI)
Multivariate OR (95% CI)a,b
P Value for Trendc
30.3 (6.1)
29.2 (5.8)d
1.03 (1.02-1.04)
1.04 (1.03-1.06)
19 (2.7) 327 (46.8) 165 (23.6) 188 (26.9)
532 (3.6) 7794 (52.4) 3738 (25.1) 2808 (18.9)
0.78 (0.59-1.04) Reference 1.01 (0.83-1.22) 1.58 (1.32-1.90)
0.75 (0.55-1.03) Reference 1.00 (0.81-1.25) 1.41 (1.13-1.77)
214 (19.5) 216 (19.7) 217 (19.8) 203 (18.5) 249 (22.7)
4862 (23.4) 4116 (19.8) 3925 (18.9) 4066 (19.6) 3792 (18.3)
Reference 1.19 (0.98-1.45) 1.26 (1.04-1.52) 1.13 (0.93-1.38) 1.49 (1.24-1.80)
Reference 1.21 (0.93-1.56) 1.43 (1.11-1.84) 1.25 (0.96-1.63) 1.39 (1.07-1.82)
899 (81.7) 27 (2.5) 126 (11.5) 48 (4.4)
15 795 (75.9) 796 (3.8) 2695 (13.0) 1528 (7.3)
Reference 0.60 (0.40-0.88) 0.82 (0.68-1.00) 0.55 (0.41-0.74)
Reference 0.72 (0.40-1.30) 0.98 (0.76-1.26) 0.78 (0.54-1.12)
828 (82.7) 79 (7.9) 75 (7.5) 19 (1.9)
16 051 (82.8) 1580 (8.2) 1312 (6.8) 432 (2.2)
Reference 0.96 (0.77-1.23) 1.11 (0.87-1.41) 0.85 (0.54-1.36)
Reference 0.96 (0.71-1.30) 1.03 (0.75-1.43) 0.81 (0.44-1.49)
459 (41.9) 636 (58.1) 97 (8.8) 96 (8.7)
11 707 (56.3) 9080 (43.7) 1290 (6.2) 1404 (6.8)
Reference 1.79 (1.58-2.02) 1.41 (1.14-1.74) 1.32 (1.06-1.64)
Reference 1.94 (1.63-2.30) 1.17 (0.87-1.58) 0.96 (0.71-1.29)
NA .001 .016 NA .628 NA NA NA
Yes
31 (2.8)
267 (1.3)
2.23 (1.53-3.25)
0.92 (0.53-1.60)
170 (15.5) 186 (16.9) 205 (18.6) 287 (26.1) 252 (22.9) 482 (43.8) 452 (41.1)
3687 (17.7) 4071 (19.6) 4125 (19.8) 4389 (21.1) 4542 (21.8) 5655 (27.2) 1873 (9.0)
Reference 0.99 (0.80-1.23) 1.08 (0.88-1.33) 1.42 (1.17-1.72) 1.20 (0.99-1.47) 2.10 (1.85-2.36) 7.05 (6.20-8.03)
Reference 0.94 (0.70-1.26) 1.12 (0.84-1.48) 1.55 (1.19-2.01) 1.25 (0.95-1.63) 1.31 (1.10-1.55) 3.54 (2.79-4.50)
.004 NA NA
565 (51.4)
3448 (16.6)
5.32 (4.70-6.02)
2.51 (2.01-3.14)
NA
Abbreviations: BMI, body mass index; CI, confidence interval; NA, not applicable; NICU, neonatal intensive care unit; OR, odds ratio; SCN, special care nursery; TSI, Torres Strait Islander. a Includes adjustment for each of the variables listed in the table. b Hosmer and Lemeshow’s goodness-of-fit test; P value = .1515 (indicates that the model fits the data well). c The P value for trend tested for a linear relation of ordinal variables using logistic regression analysis, assuming equally spaced categories. d Mean (standard deviation). e Includes mental health conditions for which women received nonpharmacological (ie, psychological/psychiatric) and/or pharmacological (ie, medications) treatment during pregnancy (eg, depression, anxiety, schizophrenia).
1.10-1.55), preterm birth (aOR = 3.54; 95% CI, 2.79-4.50), and neonatal hospitalization (aOR = 2.51; 95% CI,
2.01-3.14) (Table 1). In addition, statistically significant trends were observed between increasing socioeconomic
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Journal of Human Lactation
Figure 1. Percentage of Mothers Dispensed Domperidone according to Number of Weeks’ Gestation at Delivery.
status and year of delivery and an increased likelihood of women receiving domperidone (all Ps < .004). Preterm birth appeared the strongest predictor of domperidone use, with a significant linear relationship between decreasing gestational age at delivery and increasing percentage of mothers receiving domperidone (P < .001) (Figure 1).
Discussion Despite the widespread use of domperidone in many countries around the world, this is the first study to evaluate maternal and infant characteristics associated with its use. Factors associated with an increased likelihood of women receiving domperidone were increasing maternal age, higher socioeconomic status, maternal obesity, primiparity, year of delivery, delivery by cesarean section, preterm birth, and neonatal hospitalization. Although it is clear that domperidone should not be used as a substitute for, or as an alternative to, effective nonpharmacological breastfeeding support and encouragement,4 these findings are of clinical importance as they reinforce previous findings regarding risk factors for lactation difficulties and highlight the need for improved research regarding nonpharmacological and pharmacological interventions targeting high-risk women to improve breastfeeding outcomes. It is somewhat unsurprising that preterm birth and neonatal hospitalization remained the strongest factor associated with receiving domperidone in the multivariate analysis. It has been previously described that mothers who deliver infants who are unwell and require supportive care following delivery, such as preterm infants, are particularly vulnerable to difficulties breastfeeding.4,19 In many cases, these mothers are not able to breastfeed directly, which, in addition to the stressful situation of having an unwell infant, can have a detrimental effect on milk supply. Despite mothers of preterm infants being more likely to be prescribed domperidone than mothers of term infants,
greater than 50% of domperidone use was identified among mothers who delivered term infants who were not admitted to the NICU or SCN.14 Such high use among mothers of term infants represents an important evidence gap, as the vast majority of studies evaluating the use of domperidone have involved mothers of preterm infants only.7,9,10,19,20 Whether the findings from these studies are generalizable to mothers of term infants remains to be determined, as pharmacological needs and response could vary. It is possible that primiparous women were more likely to receive domperidone due to perceived compared to actual milk insufficiency, as can occur due to unfamiliarity with breastfeeding.4 Primiparous women may be unaware of normal postpartum physical breast changes, such as the softening of the breasts around 10 to 14 days postpartum, or misinterpret infant symptoms such as irritability, crying, and frequent feeding as a lack of breast milk quality or quantity.4 Furthermore, primiparous women, in addition to those with new or pre-existing mental health illness, may lack breastfeeding self-efficacy.21 Breastfeeding self-efficacy is influenced by numerous factors including prior breastfeeding experience, support from family and friends, and understanding of lactation physiology.4,21 If this were the case, however, one could expect these to be addressed through nonpharmacological strategies, such as education in correct infant positioning and attachment at the breast, increasing frequency of breastfeeds, and mechanical expression, rather than the use of domperidone.4 Previous studies have identified that maternal obesity may be associated with a delay in the onset of lactation, as well as a reduction in initiation of breastfeeding.22 A delay in onset of lactation could be perceived as milk insufficiency, which may explain the increased likelihood of domperidone use among these women. A notable finding was the statistically significant increasing trend of domperidone use according to year of delivery. This finding remained statistically significant even after controlling for other key factors such as preterm birth and neonatal hospitalization. It is possible that this suggests an increased prescribing of domperidone in line with a change in clinical practice/management of women experiencing lactation difficulties, rather than a change in maternal/infant risk factors alone. A limitation of this study is the reliance on hospital pharmacy dispensing data to identify domperidone use. This is likely an underestimate of the total number of women who received domperidone, as some may have been prescribed domperidone outside of the hospital. The identification of such use in the community setting would be of particular interest. Second, no data were available on whether women saw a lactation consultant. Data from a previous study undertaken at the same hospital, however, identified that 40% of the mothers who received domperidone were admitted to a breastfeeding unit and/or received specialist advice from a lactation consultant.14 It is important to note that the aim of this study was not to evaluate the appropriateness of domperidone use.
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Grzeskowiak et al
Conclusion This study provides a significant contribution to the literature by looking beyond factors that are associated with breastfeeding itself, but rather at factors essentially associated with lactation difficulties, of which domperidone use can be used as a marker. Future research is required to explore why particular subgroups of women are at risk of experiencing lactation difficulties and are more likely to require treatment with domperidone. Furthermore, given the widespread use of domperidone, additional evidence is required regarding the safety and efficacy (dose, duration of treatment, time to initiate domperidone) to support the development of evidence-based guidelines.12 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: The authors wish to acknowledge salary support through a National Health and Medical Research Council Australian Public Health Fellowship (ID 1070421 to LEG).
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