Nonpharmacologic Factors Affecting Milk Production in Pump-Dependent Mothers of Critically Ill Infants

State of the Science

Abstract

Background: 

Improved health outcomes for critically ill infants including neurodevelopmental, immunological, and cost benefits are dependent upon the dose and duration of mother's own milk feedings. However, mothers of infants admitted to the neonatal intensive care unit (NICU) must express their milk (pump-dependent) and often struggle with milk production.

Purpose: 

To examine the state of the science on nonpharmacologic modifiable expression factors that may influence milk production in pump-dependent mothers of critically ill infants admitted to the NICU.

Data Sources: 

PubMed, Embase, and CINAHL databases from 2005 to 2020.

Search Strategy: 

Guided by the lactation conceptual model, the authors searched for peer-reviewed studies with terms related to milk volume, pump dependency, critically ill infants, and modifiable factors, which may influence milk volume and assessed 46 eligible studies.

Data Extraction: 

Data were extracted by 3 reviewers with a systematic staged review approach.

Results: 

Evidence from 26 articles found expressed milk volume may be influenced by multiple potentially modifiable factors. Simultaneous expression with a hospital-grade electric pump at least 5 times per day beginning 3 to 6 hours after delivery, and adding complementary techniques including hand expression, hands-on-pumping, music, breast massage, warm compresses, skin-to-skin care, and the mother expressing near her infant may promote increased milk volume.

Implications for Practice and Research: 

Healthcare providers should assist pump-dependent mothers with early initiation and frequent milk removal with a hospital-grade breast pump. Further research is needed to explore optimal frequency of expressions, dose and timing of skin-to-skin care, and other targeted strategies to improve expressed milk volume.

The American Academy of Pediatrics recommends all infants receive exclusive human milk feedings for the first 6 months including donor human milk (DHM) for preterm infants when mother's own milk (MOM) is not available.¹ The use of MOM compared with pasteurized DHM or formula improves outcomes for infants who are admitted to the neonatal intensive care unit (NICU) related to decreased late-onset sepsis,² necrotizing enterocolitis, and overall morbidity, as well as increased gastrointestinal and cognitive development.³ Most health benefits are dependent upon dose and duration of MOM feedings^2,3; therefore, it is imperative to prioritize MOM for infant feedings. Yet regardless of an infant's gestational age (GA) at birth, insufficient milk production is a mother's primary reason for supplementation and lactation cessation.^4,5 Insufficient milk production is defined as a state in which a mother produces or perceives that she produces an inadequate milk volume to meet the nutritional needs of her infant. For mothers of preterm infants, early postpartum diminished milk production is associated with an over 6 times greater odds of formula feeding at discharge.⁴

The World Health Organization estimates more than 1 in 10 infants are born premature.⁶ The preterm birth rate in the United States rose from 9.57% in 2014 to 10.02% in 2018.⁷ This increase has primarily been attributed to an escalation in late preterm births (34-36 weeks).⁸ Along with the rising prematurity rate, admission rates to the NICU have increased for all GAs.⁹ However, the highest acuity and cost of NICU care are inversely associated with GA.⁹ For an infant born less than 28 weeks' gestation, the reported average NICU cost is over $100,000.⁹ An increase in the amount of MOM an infant receives by as little as 10 mL/kg/day while admitted to the NICU has been associated with lower hospitalization costs of approximately $10,000.⁹ The dose-dependent health and cost advantages of MOM² suggest that feeding infants MOM benefits the infant and ultimately, the long-term cumulative advantages suggest benefits to the health and economy of society.

A mother whose infant is admitted to the NICU is often unable to breastfeed her infant due to physical separation,¹⁰ poor oral motor development, prematurity, and/or illness.^4,11 Therefore, mothers must rely on expression of milk via a breast pump to establish and maintain an adequate milk supply for purposes of lactation for their high-risk infants, otherwise known as pump dependency.¹² The first weeks following delivery are important because the mammary gland epithelial cells undergo programming processes,¹³ suggesting prolonged milk production is influenced by early and effective milk removal.¹⁴ Hill et al¹⁵ reported milk volume in mothers of preterm infants declined from weeks 3 through 6 postpartum, compared with a negligible milk volume decline during week 6 seen in mothers of breastfeeding term infants. Mothers of infants admitted to the NICU have described expressing milk negatively as burdensome, time-consuming, and difficult.¹⁶ Nonetheless, these mothers have described expressing milk positively as a source of connection and maternal identity.¹⁷ However, pump-dependent mothers whose infants are admitted to the NICU often struggle with sustaining an adequate milk production over time, likely resulting in DHM or formula supplementation potentially reducing neurodevelopmental, immunological, antimicrobial, and cost benefits² of MOM feedings.³ Examining modifiable factors that may influence MOM production in pump-dependent mothers is fundamental to identifying and prioritizing evidence-based lactation care to increase lactation success and thus improve infant outcomes. Therefore, the purpose of this state-of-the-science review is to examine and critically analyze the evidence on the effect of modifiable expression factors on milk production in pump-dependent mothers of critically ill infants admitted to the NICU and to provide implications for clinical practice and future research.

CONCEPTUAL MODEL

This state-of-the-science review is guided by the lactation conceptual model pioneered by Hill et al¹⁸ to critically review factors that may influence milk production in pump-dependent mothers of infants admitted to the NICU. The model uses activator events, which are primary stressors capable of initiating substantial physical or psychological reactions and mediators, which are defined as filters or modifiers that may explain variations in an individual's responses.¹⁸ A mother's reaction to the birth of an infant admitted to the NICU has physiological (hormonal) and psychosocial (stress) responses that may affect her lactation experience. In this model, mediators are variables occurring before delivery identified as primary mediators or after delivery identified as secondary mediators, which potentially have a positive or negative influence on milk volume and may explain individual differences in milk production.¹⁸ Primary mediators are generally nonmodifiable and include maternal characteristics such as age or income. Secondary mediators are potentially modifiable such as time to initiation of expression, frequency of expression, and skin-to-skin care. This review examined secondary mediators related to milk expression that can potentially be modified and may affect milk production.

REVIEW OF THE LITERATURE

A systematic staged review approach¹⁹ by 3 reviewers was used to implement a well-defined comprehensive search of published literature. The primary databases searched included PubMed, Embase, and CINAHL. A secondary search was conducted by hand from the references of included articles. In addition, a librarian was consulted to assist in defining search terms, identifying relevant databases, and applying a systematic search. The MeSH, primary, and related search terms included mothers own milk, breast milk, human milk, lactation, milk expression, expression, lactation, breastfeeding, colostrum, pump, pump dependent, breast milk expression, mothers own milk expression, volume, amount, production, supply, NICU, and intensive care, neonatal. Boolean operators were applied to combine and define the search terms. Search limiters were applied depending on the database to include English language, humans to exclude animal studies, peer reviewed, and research articles to narrow the search to relevant sources.

Articles published between January 2005 and December 2020 were included if the study population was comprised of pump-dependent mothers delivering an infant admitted to the NICU and contained results related to MOM production. This review included articles over the last 15 years to capture sentinel milk volume research. Included articles needed to be peer-reviewed randomized controlled trials (RCTs) or observational studies that were obtainable in English and full text. Articles were excluded if the study's purpose was to examine maternal/infant outcomes related to breastfeeding or the receipt of MOM upon or after NICU discharge, as well as breast pump brand comparison. Studies related to galactagogues known as substances that may increase milk production are beyond the scope of this review and were excluded.

The primary reviewer (M.M.B.) screened the titles and/or abstracts based on inclusion and exclusion criteria, and then full-text articles were obtained for further review. Two secondary reviewers (L.C.I. and L.A.P.) independently reviewed full-text articles. Articles selected for critical analysis were determined by reviewer consensus. A visualization of the study selection process is presented in Figure 1.¹⁹

FIGURE 1: PRISMA 2020 flow diagram of study selection.¹⁹

RESULTS

This literature review yielded 26 studies that met the inclusion and exclusion criteria for critical analysis. Six studies were RCTs^20–25 of which 3 were pilot studies. One²⁶ was a secondary analyses of an RCT and the remaining 19 were observational cohort studies. Studies originated from 13 different countries, with 11 from the United States. See Table 1 for a summary of included studies.

TABLE 1. - Summary of Included Studies

Authors and Location	Study Design and Purpose	Methods and Sample Population
Acuña-Muga et al10 Spain	Observational prospective cohort To investigate the effect of expression in proximity to infants and STS on MV	Mothers (n = 26) of very low birth-weight infants, 28.7 ± 2.4-wk GA recorded MV, whether the expression sessions occurred during or after STS, and where the expression sessions occurred in proximity to her infant for 10 d
Bishara et al27 Canada	Prospective descriptive To describe foremilk, hindmilk, and total MV in relation to expression factors	24 mothers of infants <28-wk GA and 21- to 30 d old who expressed ≥4x/d and whose MV exceeded their infants' needs by 20%. Mothers recorded MV for 24 h.
Divya et al28 India	Quasi-experimental, time series To determine the effect of breast massage on MV	30 mothers used breast massage with warm compresses during 3 expression sessions 3-8 d postpartum. MV was measured using a measuring cup and compared with MV from 3 sessions with no massage/warm compresses.
Fewtrell et al26 United Kingdom	Secondary analysis To investigate factors predicting MV during the first 10 d postpartum and during the infant's entire hospital stay	62 mothers of infants 24- to 34-wk GA recorded STS episodes, MV (determined by weight), expression session duration, and whether simultaneous or sequential expression was used in a diary for 10 d postpartum. 47 mothers recorded information until infant discharge.
Henderson et al29 Australia	Prospective cohort To explore 24-h MV over 10 d	50 mothers of infants 24.2- to 33.7-wk GA recorded milk weight, frequency, and duration of expressions in a diary for 10 d after delivery.
Hill and Aldag30 USA	Longitudinal cohort To determine whether d 4 expression frequency and MV predicted wk 6 MV adequacy	81 mothers of infants <1500 g and ≤31-wk GA recorded MV and time of expressions in a logbook. Information regarding STS during d 1-7 was obtained via questionnaire.
Hill et al15 USA	Observational prospective cohort To determine whether MV wk 1 through wk 6 differs by GA	Mothers of infants ≤31-wk GA (n = 95) and mothers of healthy breastfeeding term infants (n = 98) recorded MV and expression or breastfeeding duration for 6 wk.
Hill et al14 USA	Observational cohort To compare MV, expression frequency and hormone levels between mothers of preterm and term infants	Pump-dependent mothers of infants ≤31-wk GA (n = 95) and breastfeeding mothers of term infants ≥37-wk GA (n = 98) recorded MV and expression frequency and/or breastfeeding in a logbook for 6 wk.
Hoban et al31 USA	Pilot observational To describe relationships between biomarkers, MV, and expression frequency for d 1-14 postpartum	16 mothers of infants <33-wk GA recorded expression duration in a pumping log for 14 d, MV volume was determined by weighing vials of milk (by nursing staff).
Jayamala et al32 India	Quasi-experimental To evaluate the effect of music therapy on MV	30 mothers of infants <34-wk GA listened to music before and during 4 of 8 expression sessions over 4 d. MV measured using vial gradations.
Keith et al20 USA	Pilot RCT To explore the effect of 3 musical interventions on MV	162 mothers of infants <38-wk GA were randomized to 1 of 4 interventions (guided relaxation and lullabies; infant images, guided relaxation and lullabies; guided relaxation; or standard care). Mothers recorded MV for 14 d.
Köroğlu et al33 Turkey	Descriptive quasi-experimental To compare sequential vs simultaneous expression on MV	Mothers (n = 35) of infants 25- to 38-wk GA self-selected to either simultaneous or sequential expression. Recorded MV, frequency, and expression duration for 10 d.
Lai et al34 Australia	Observational cohort To determine the effect of expression regimes on MV during early lactation	25 mothers of infants <34-wk GA recorded expression session duration and MV on d 10 and d 15-20 postpartum. MV was determined by weight.
Lau et al35 USA	Observational cohort To determine associations between MV, STS, and lactation duration	124 mothers of infants 26- to 29-wk GA recorded daily MV and expression frequency over 10 wk postpartum and information on STS during infant hospitalization.
Lussier et al21 USA	Pilot RCT To compare MV using HE vs EE d 1-7 and 28 d post-delivery	40 mothers (HE n = 12, EE n = 14) of infants ≤1500 g and ≤32-wk GA recorded MV, time of expression, and method of expression (HE or EE) in a logbook.
Morton et al36 USA	Observational prospective cohort To determine whether HE of colostrum and hands-on-pumping of mature milk affects MV over 8-wk postpartum	67 mothers of infants <1500 g and <31-wk GA recorded time of expression and MV for 8 wk. A subset of mothers (n = 42) began hands-on-pumping at 20.6 ± 9.6 d into the study.
Murase et al37 Japan	Retrospective chart review To examine MV d 1-4 and mother's own milk at NICU discharge	Expression frequency, time to first expression and MV for the first 4 d after delivery was extracted from the medical records of 87 mothers of infants <32-wk GA.
Parker et al22 USA	Pilot RCT To compare MV between mothers who initiated expression ≤1 h vs 1-6 h following delivery over 6 wk	Mothers of infants <32-wk GA and <1500 g were randomized to initiate expression <1 h (n = 10) or 1-6 h (n = 10) after delivery. MV was measured by weight on d 1-7, and weekly for 6 wk.
Parker et al38 USA	Pilot prospective cohort To determine the effect of time to initiation of expression on time to SA and MV over 6 wk	40 mothers of infants <1500 g and <32-wk GA initiated expression <6 h (n = 20) or >6 h (n = 20) after delivery. MV was measured by weight on d 1-7 and weekly for 6 wk.
Parker et al24 USA	RCT To determine the effect of time to expression initiation on time to onset of SA and MV over 6 wk	180 mothers of infants ≤1500 g and ≤32-wk GA were randomized to initiate expression ≤1 h (n = 58), >1-3 h (n = 62), or >3-6 h (n = 60). MV was measured by weight on d 1-7 and weekly for 6 wk.
Post et al39 Netherlands	Observational cohort To compare MV between use of S-BPSP and I-BPSP	130 mothers of term (n = 19), late preterm (n = 44), and preterm (n = 67) infants who used an S-BPSP (n = 64) or I-BPSP (n = 66) until SA. Mothers recorded MV d 1-14.
Ru et al40 China	Observational prospective cohort To investigate relationship of MV with time to first expression, expression frequency, and time to onset of SA	30 mothers of infants <1500 g and <32-wk GA recorded expression frequency and duration and MV by weight in a diary on d 1-14, d 21, 28, 35, and 42 postpartum.
Slusher et al23 Kenya/Nigeria	RCT To compare MV using electric BP, nonelectric pedal BP, and HE	65 mothers of infants 26- to 40-wk GA were randomized to use an electric BP (n = 21), pedal pump (n = 24), or HE (n = 18). MV was measured using a graduated scale on bottles for 10 d.
Slusher et al41 Uganda	Quasi-experimental To compare MV between 3 milk expression techniques: double electric BP, single manual BP, and HE	161 mothers of infants (GA not reported) were randomized to double electric BP (n = 55), single nonelectric manual BP (n = 59), or HE (n=47). MV was measured using a graduated scale on bottles for 7 d.
Varişoğlu and Güngör Satilmiş25 Turkey	RCT To compare the effect of listening to music on MV over 4 d	40 mothers of infants 28- to 34-wk GA were randomized to listen to music (n = 20) or no music (n = 20) during 2 expression sessions a day for 3 d.
Yigit et al42 Turkey	Quasi-experimental To investigate the effect of warm compresses on MV	39 mothers of infants <21 d old were randomized to apply a warm compress for 20 min to one breast before 2 expressions a day for 3 d. MV was measured by graduated scale on bottle.

Abbreviations: BP, breast pump; EE, electric pump expression; GA, gestational age; HE, hand expression; I-BPSP, irregular breast pump suction pattern; MV, milk volume, NICU, neonatal intensive care unit; RCT, randomized controlled trial; SA, secretory activation; S-BPSP, standard breast pump suction pattern; STS, skin-to-skin care.

Although all studies included pump-dependent mothers of infants admitted to the NICU, 13 included only mothers of very low birth-weight (VLBW, <1500 g) infants. Therefore, the evidence provided from this review is primarily based upon research examining mothers delivering VLBW infants less than 32 weeks' GA. Furthermore, when researchers reported milk volume in grams, the results were equated to milliliters (1 mL = 1 g) for greater uniformity between study results.

TIMING OF INITIATION AND FREQUENCY OF EXPRESSION

Timing of initiation of the first expression session following delivery and expression frequency are potentially modifiable factors that may affect establishment and subsequent maintenance of milk production. See Table 2 for a summary of key findings.

TABLE 2. - Effect of Timing of Initiation and Frequency of Expression

Authors	Key Findings
Timing of initiation of first expression
Hill and Aldag30	Earlier time to initial expression (r s=−0.22, P = 0.05) was positively predictive of milk adequacy (defined as ≥500 mL/d) at wk 6.
Murase et al37	Median time to first expression was 20 h (8-29) postpartum with 36% of mothers beginning expression after 24 h postpartum. Milk expression initiation <6 h was not associated with low milk volume on d 4 (<153 mL).
Ru et al40	MV on d 7, 14, and 42 was similar between mothers initiating expression <6 h and >6 h. (7.6 h, range 4.6-10.3).
Parker et al22	Mothers who began milk expression <1 h after birth had greater MV during the first week postpartum (1374.7 vs 608.1 mL; P = .05) and at wk 3 (P < .01) than those who began expressing 1-6 h after birth and had an earlier onset of SA (80.4 h vs 136.8 h; P = .03).
Parker et al38	Initiation of expression <6 h after delivery was associated with greater MV on d 6 (P = .001) and 7 (P = .006). Initiation of expression <6 h was associated with greater MV during d 1-7 (P = .076) and at 6 wk (P = .05) but was not statistically significant. Expression initiation <1 h after delivery (n = 10) was associated with greater MV compared to initiation 1-6 h (n = 10) or >6 h (n = 20) at d 7 (306.2, 244.0-384.3 vs 180.7, 80.8-253.2, vs 125.7, 65.3-192.7; P = .005) at wk 3 (543.5, 466.1-818.1 vs 238.9, 87.8-442.0 vs 224.3 mL, 100.7-334.8; P = .007) and wk 6 (440.0, 352.1-526.4 vs 209.0, 64.1-355.8 vs 258.7 mL, 124.3-284.7; P = .024).
Parker et al24	Initiation of expression 3-6 h after delivery was associated with increased MV d 1-3 (P = .031) and at 6 wk (P = .045) compared to initiation at <1 h but was similar to initiation between 1 and 3 h.
Breast expression frequency
Bishara et al27	Total MV did not correlate with milk expression frequency or longest time between expressions.
Hill et al15	Mothers of preterm infants expressed fewer times/d than mothers of term infants (either expressed or breastfed) across all weeks (P < .001).
Hill et al14	MV was positively related to expression frequency in mothers of both preterm and term infants (P < .001; P < .001, respectively).
Fewtrell et al26	MV was positively predicted by greater number of expressions during the first 10 d (r = 0.43, P = .001) and throughout the infant's hospital stay (r = 0.36, P = .01).
Lussier et al21	Daily expression frequency between groups was similar. Daily MV was positively associated with daily expression frequency (coefficient 25, 95% CI: 14 to 37; P < .001), with each expression session adding an adjusted 25 mL to daily MV.
Hill and Aldag30	Greater d 4 expression frequency (r s= 0.32, P < .01) was positively predictive of milk adequacy (defined as ≥500 mL/d) at wk 6.
Murase et al37	≥4 expressions d 2 was associated with MV (median ≥153 mL) on d 4 (P = .02).
Lau et al35	Daily expression frequency (4.6 ± 1.3 to 5.7 ± 1.2 times/d) was positively correlated with 24-h MV (P = .001).
Morton et al36	HE >5 times/d vs <2 times/d or 2-5 times/d on d 1-3 postpartum was associated with greater MV during wk 2 (710 ± 402 vs 392 ± 196 mL, P < .005; 448 ± 318 mL, P = .023, respectively) and greater MV on d 14 but not at wk 8. MV at 8 wk was positively associated with BP expression frequency (P = .002), expression session duration (P = .033), and longest interval between expression sessions (P < .01). ≥7 expressions/d was associated with higher MV compared to <7 times/d at 2 wk (P = .030) but not 8 wk (P = .170).
Hoban et al31	Mother who achieved MV >500 mL/d by d 14 compared with mothers who did not had increased expression frequency d 1-5 (P < .001) and d 1-14 (P = .03). Mothers who expressed ≥5 vs <5 times/d were more likely to achieve >500 mL/d by d 14 (P = .01).
Lai et al34	MV was greater on d 10 and 15-20 with 6 vs 3 expressions/d (228 mL, 95% CI: 414 to 43; P = .006), 7 vs 3 (26.9 mL, 95% Cl: 11 to 9; P < .001), 5 vs 4 (170 mL, 95% CI: 298 to 42; P = .002), and 6 vs 4 expressions/d (223 mL, 95% CI: 370 to 77; P < .001). No statistically significant daily MV difference between 3 vs 4 or 5 or between 5, 6, 7, 8, and 9 expressions/d.
Henderson et al29	Over 10 d, 24-h MV was positively associated with expression frequency (P < .001). Mothers who expressed ≥6 times/d vs <6 times/d produced greater MV.
Ru et al40	Expression frequency of ≥6 vs <6 times/d was associated with greater MV on d 42 (1178.7 vs 557.5 mL, t =−2.828, P = .009).

Abbreviations: BP, breast pump; CI, confidence interval; HE, hand expression; MV, milk volume; SA, secretory activation.

Timing of Initiation of First Expression

Baby-Friendly Hospital Initiative (BFHI) practices were developed to improve lactation success and recommend initiation of breastfeeding within 1 hour after delivery.¹¹ When breastfeeding is impossible due to mother–infant separation, recommendations include instructing mothers on initiation of breast expression.¹¹ The onset of secretory activation is the transition from production of small amounts of colostrum to copious amounts of MOM. Six studies examined the effect of time to the initial expression session following delivery on milk volume in mothers delivering infants less than 33 weeks' GA (Table 2).^{22,24,30,37,38,40} While one small pilot RCT suggests initiation within 1 hour after delivery increases milk production and decreases time to onset of secretory activation,²² a recent adequately powered RCT found no benefit to expression within 1 hour.²⁴ In this study, mothers who initiated expression 3 to 6 hours after delivery produced more milk over the first 6 weeks compared with those who initiated at less than 1 hour (P = .045). However, mothers who initiated expression 3 to 6 hours after delivery expressed more frequently over the first 5 days, which may have positively affected milk production. In contrast, findings from a small (n = 30) observational study⁴⁰ reported no differences in milk production on postpartum days 7, 14, or 42 between mothers who initiated expression within 6 hours of delivery compared with those who initiated more than 6 hours postpartum. In mothers who initiated expression more than 6 hours postpartum, 43% initiated 6 to 12 hours and 17% more than 12 hours after delivery. However, the study's small sample size may have limited detection of statistically significant differences. Two studies (n = 81³⁰ and n = 87³⁷) reporting a positive association between milk volume and earlier initiation of expression found approximately 50% of participants initiated expression more than 24 hours postpartum, suggesting mothers may experience challenges initiating expression within the recommended 6 hours.¹¹ The evidence of 2 observational studies supports earlier expression initiation; furthermore, 1 observational study and 2 RCTs support that expression initiation within 6 hours following delivery is optimal and thus studies to explore interventions to implement early initiation of expression are needed.

Breast Expression Frequency

Frequent and effective milk removal is necessary to prevent accumulation of the polypeptide feedback inhibitor of lactation within the breast leading to a reduction in milk production.⁴³ Although BFHI recommends mothers breastfeed 8 to 12 times a day, recommendations for mothers delivering infants admitted to the NICU include expressing “frequently,” but the exact number of recommended expressions per day is not provided.¹¹ Thirteen studies examined the effect of expression frequency on milk production with 12 studies, finding a positive relationship between number of expressions per day and volume of milk produced (Table 2). Hill et al¹⁵ found in their sentinel study that mothers of preterm infants expressed less frequently than mothers of term breastfeeding infants over 6 weeks (5.7-6.05 vs 8.0-8.9 times/day; P < .001) and were 2.8 times more likely to produce a milk volume of less than 500 mL/day by week 6. However, Bishara et al²⁷ found that while 92% of 24 mothers expressed at least 6 times during the 24-hour study period, total milk volume was not related to expression frequency or longest time between expressions. This descriptive study²⁷ included a small sample size, was conducted over a short period (24 hours), and included mothers who had been expressing milk for at least 3 weeks, which may have limited variability in milk production and expression frequency.

Expression frequency during the first few days after delivery may be associated with milk production. In their study of 85 mothers of infants 27.6 to 30.6 weeks' gestation, Murase et al³⁷ found expression frequency on day 2 postpartum was positively associated with milk volume on day 4 (P = .02) and mothers who expressed fewer than 4 times on day 2 had lower milk volume on day 4 compared with those who expressed at least 4 times (median <153 vs ≥153 mL; P = .02). Likewise, in an observational study of 81 mothers of infants less than 32 weeks' GA, day 4 expression frequency was associated with a milk volume of at least 500 mL/day during week 6 (r_s= 0.32; P < .01).³⁰

Expression frequency prior to the onset of secretory activation may be associated with milk production during the first few weeks following delivery. Morton et al³⁶ found mothers of infants less than 31 weeks' GA (n = 67) who used a combination of an electric breast pump and hand expression prior to the onset of secretory activation produced more daily milk volume at week 2 postpartum when they expressed at least 5 times per day during the first 3 days postpartum compared with those who expressed fewer than 2 times per day (710 vs 392 mL; P < .005) or between 2 and 5 times per day (710 vs 448 mL; P = .023). Furthermore, mothers who expressed at least 7 times per day produced a greater daily milk volume at 2 weeks (622 vs 402 mL; P = .03) but not at 8 weeks postpartum (1019 vs. 752 mL; P = .17), suggesting more frequent expressions may have a greater influence on establishment, rather than maintenance of milk production.

Several researchers^29,31,40 have reported an association between an expression frequency of greater than 5 times per day and increased milk production. In 124 mothers of infants born between 26 and 29 weeks' GA, Lau et al³⁵ found a positive correlation (P = .001) between daily expression frequency (4.6-5.7 times/day) and 24-hour milk volume at weeks 2, 4, 6, 8, and 10, but no correlation existed between expression frequency and whether or not mothers continued expressing through their infant's hospitalization. A small observational study³⁴ of 25 mothers of preterm infants (24-32 weeks' GA) found expressing 6 times/day was associated with a greater daily milk volume on day 10 and days 15 to 20 than expressing 3 times/day (P = .006). Likewise, expressing 7 times/day was associated with greater milk production per expression compared with 3 times/day (P < .001). However, there was no per-expression milk volume difference between 7, 8, or 9 expressions per day. Similarly, researchers found, in a small RCT (n = 36), expression frequency ranged from 1 to 10 times per day during the first 28 days postpartum and that each additional expression was associated with a daily milk volume increase of 25 mL (P < .001).²¹ Based upon the results of 13 studies, while expressing at least 5 times per day may be sufficient to maintain milk production, mothers who express at least 6 times per day likely produce greater daily milk volume.

EXPRESSION METHODS

Expression methods are techniques implemented to remove milk from the breast and include hand expression, hands-on-pumping, type of breast pump used, and whether sequential or simultaneous expression is performed. The type of expression method used may influence milk volume by eliciting a milk ejection reflex (MER) and promoting effective milk removal. An MER is a neurohormonal reflex stimulated by oxytocin released from the posterior pituitary leading to alveolar myoepithelial cell contracture and milk release.⁴³ Only minimal amounts of milk can generally be removed before the first MER occurs and the number of MERs occurring during a single expression session is associated with the volume of milk removed from the breast.^43,44 During expression, oxytocin release can occur from direct nerve intervention by areolar/nipple stimulation or indirectly from a conditioned response related to stimulus, such as hearing an infant cry.⁴³

Milk removal can be performed using hand expression, hands-on-pumping, and/or a manual or electric breast pump. Hand expression refers to rhythmically compressing and releasing the breast to remove milk.³⁶ Simultaneous expression is expressing both breasts at the same time and sequential expression is expressing one breast at a time during an expression session. Hands-on-pumping is a multistep expression technique beginning with simultaneous breast expression using an electric breast pump while concurrently using breast compression and massage followed by breast massage and hand expression after cessation of milk flow to remove any remaining milk.³⁶ Two main types of breast pumps are available for use, including manual that requires mothers to manually cycle and control suction and electric that uses electricity for cycling and suction. While not common, pedal breast pumps use a foot pedal for manual cycling with a spring cylinder for suction and have been used in NICUs in developing countries.²³ This review found 7 studies investigating the effect of different expression methods on milk production in mothers delivering infants admitted to the NICU (Table 3).

TABLE 3. - Effect of Expression Methods

Authors	Key Findings
Breast pump vs hand expression
Lussier et al21	Exclusive EE compared to exclusive HE over the first week was associated with greater daily MV (P < .05) and cumulative MV (1371 vs 456 mL; P = .003) d 1-7 postpartum and higher MV of 119 mL/d (coefficient −119, 95% CI: −175 to −63; P < .001) and cumulative MV d 1-28 (13,639 [3020, 17,770] vs 7208 mL [4240, 14,279]).
Slusher et al23	Use of a double electric BP was associated with greater daily MV over 10 d than HE (578 vs 323 mL; P < .01). Similar MV was obtained between an electric BP and pedal pump (463 mL) and between pedal pump and HE.
Slusher et al41	Mothers who expressed using a double electric BP had greater daily MV over 7 d than mothers using HE (647 vs 434 mL; P < .01), but similar to those using a single nonelectric manual BP (520 mL). Similar MV was obtained between mothers expressing with single nonelectric manual BP and HE.
Combining the use of breast pumps with hand expression or hands-on-pumping
Morton et al36	Hands-on-pumping was associated with increased daily MV (583 ± 383 to 863 ± 506 mL; P <.003).
Simultaneous vs sequential expression
Fewtrell et al26	MV was positively predicted by simultaneous vs sequential expression (109 mL/d, 95% CI: 31 to 186; P = .007) on d 1-10 (288 [168, 386] vs 147 mL/d [78, 275]) and during the infant's hospital stay (218 mL/d, 95% CI: 80 to 356; P = .003; 561 (202, 708) vs 220 (112, 349) mL/d).
Köroğlu et al33	Mothers who expressed using simultaneous vs sequential expression achieved similar MV in a shorter amount of time (11.57-15.62 min vs 18.16-20 min).

Abbreviations: BP, breast pump; CI, confidence interval; EE, electric breast pump expression; HE, hand expression; MV, milk volume.

Breast Pump Versus Hand Expression

Three studies compared the use of hand expression versus a breast pump on milk production. In 2 separate studies, Slusher and colleagues compared the effect of 4 expression methods (hand expression, electric breast pump, manual breast pump, and pedal pump) on milk volume. In the first study, 65 mothers of infants 26 to 40 weeks' GA admitted to the NICU were randomized to use either an electric breast pump, hand expression, or a pedal breast pump during the first 10 days postpartum.²³ They found statistically significant differences in milk volume between groups (P = .014), with electric breast pumps being associated with higher daily milk volume than hand expression (578 vs 323 mL; P = .001) but not compared to pedal pumps.²³ The second, a quasi-experimental study of 161 Ugandan mothers of critically ill infants (no GA reported) who were sequentially assigned to use an electric breast pump, a manual breast pump, or hand expression over the 7-day study found mothers who used an electric breast pump produced more daily milk volume than mothers who used hand expression (647 vs 434 mL; P = .01) but similar milk volume as mothers who used a manual pump.⁴¹ Similarly, Lussier et al²¹ found mothers who used an electric pump produced more milk than those who performed hand expression over the first week (cumulative median 1371 vs 456 mL; P = .003) but not at week 2 or 15 to 28 days postpartum. However, median cumulative milk volume over the first 28 days postpartum was lower in mothers who used hand expression compared with those using an electric pump during the first week (7208 vs 13,639 mL), which may be clinically important.²¹ Together, these 3 studies suggest greater milk volume may be obtained with the electric breast pump than hand expression, manual pump, or pedal pump.

Combining the Use of Breast Pumps With Hand Expression or Hands-On-Pumping

Few researchers have examined using hand expression in combination with an electric breast pump or the use of hands-on-pumping. In mothers (n = 67) of infants less than 31 weeks' GA, Morton et al³⁶ found those who used hand expression greater than 5 times per day combined with breast pumping during the first 3 days postpartum compared with those who did not hand express or did so fewer than 2 times per day was associated with an increase in mean daily milk volume during week 2 (710 vs 392 mL; P = .017) and week 8 (955 vs 658 mL; P = .06). In a subset analysis of 42 mothers who began using hands-on-pumping at 3 to 4 weeks postpartum, milk volume was increased at 8 weeks postpartum when compared with 3 days prior to initiation of hands-on-pumping (583 vs 863 mL; P < .003).³⁶ Evidence from only one observational study supports combining hand expression with an electric breast pump during the first 3 days postpartum, followed by hands-on-pumping with an electric breast pump as an important expression method to increase and maintain milk volume. However, additional research is needed to confirm results.

Simultaneous Versus Sequential Expression

Two studies examined the effect of sequentially expressing one breast at a time versus simultaneous expression of both breasts on milk production.^26,33 One small observational study³³ found no difference in milk volume between simultaneous and sequential expression during the first 10 days postpartum in 35 mothers of infants 25 to 38 weeks' GA. However, the duration of expression sessions was shorter for simultaneous expression (11.57-15.62 minutes) than for sequential expression (18.16-20 minutes). Conversely, an RCT (n = 62) reported simultaneous compared with sequential expression resulted in greater daily milk volume over 10 days (288 vs 147 mL/day; P = .007).²⁶ Based on these findings, simultaneous expression may decrease the time necessary for milk expression, but the effect on milk production is unclear. It is possible that simultaneous milk expression may influence milk production by stimulating a bilateral MER, which may increase the number of MER events in a single expression session.

COMPLEMENTARY EXPRESSION STRATEGIES

Complementary expression strategies are methods aimed at eliciting the first MER and increasing the number of MER occurrences during an expression session, thus potentially increasing volume of milk produced. Complementary expression strategies include breast pump suction pattern (BPSP) technology, breast massage, warm compresses, relaxation techniques, and skin-to-skin care. For the purposes of this review, relaxation techniques will include environment and music therapy due to their potential relationship to stress and anxiety and effect on MER and thus milk volume. See Table 4 for key findings.

TABLE 4. - Effect of Complementary Expression Strategies

Authors	Key Findings
Breast pump suction patterns
Post et al39	The I-BPSP group had greater MV d 3-14 (P < .001), experienced an earlier onset of SA (3.3 ± 0.6 vs 4.5 ± 2.1 d; P < .001) and reached an MV of >500 mL/d earlier (7.7 ± 2.4 vs 9.5 ± 3.0 d; P < .01).
Breast massage and application of warm compresses
Divya et al28	Mothers expressed greater MV during the sessions with massage and warm compresses (15.56 ± 8.38 vs 7.33 ± 4.86 mL; P = .001).
Yigit et al42	During each of the 6 expression sessions, the warm compress breast produced greater MV (P < .001). Differences were greatest on the fifth of 6 expressions on d 3 (47.02 ± 23.01 vs 33.15 ± 19.98 mL; P < .001).
Environment and relaxation therapies
Acuña-Muga et al10	The first expression of the day had the greatest MV (difference, 38.5 mL; 95% CI: 33.1 to 44.0 mL; P < .001) and when expression occurred in proximity vs far from infant (adjusted difference, 3.82 mL; 95% CI: 0.05 to 7.58 mL; P = .046) or when expressing at the infant's bedside vs at home (101.2 mL, 95% CI: 88.1 to 114.3 vs 97.4 mL, 95% CI: 84.3 to 110.5; P = .046).
Keith et al20	Mothers in the 3 experimental groups produced more milk over the 14 d than the control group (P < .001).
Jayamala et al32	Mothers produced greater MV during the 4 music vs 4 no music expression sessions (7.12 vs. 6.68 mL; P = .033).
Varişoğlu and Güngör Satilmiş25	MV was greater in the music group compared with on the third to fourth days (23.1 ± 14.1 vs 12.3 ± 11.8 mL; P = .001).
Skin-to-skin care
Acuña-Muga et al10	MV was greater when mothers expressed during STS vs at their infant's bedside (difference, 11 mL; 95% CI: 4.8 to 17.2; Bonferroni adjusted P = .003) and after STS vs at their infant's bedside (difference, 21 mL; 95% CI: 9.5 to 32.6; Bonferroni adjusted P < .001). There was no difference in MV when mothers expressed during STS vs after STS or between expressions when far from the infant either at home or in the hospital but not at infant bedside.
Fewtrell et al26	Positive predictors of MV included more STS episodes on d 1-10 and during the infant's hospitalization (r = 0.34 P = .007; r = 0.26 P = .08; respectively).
Hill and Aldag30	STS during wk 1 (r s= 0.33, P < .01) was positively predictive of milk adequacy (defined as ≥500 mL/d) at wk 6.
Lau et al35	Time in STS was positively associated with 24-h MV (P = .020) and whether or not mothers continued expressing until infant discharge (P = .048, odds ratio = 1.05, 95% CI: 1.00 to 1.10).

Abbreviations: BP, breast pump; CI, confidence interval; EE, electric breast pump expression; HE, hand expression; I-BPSP, irregular breast pump suction pattern; MV, milk volume; SA, secretory activation; S-BPSP, standard breast pump suction pattern; STS, skin-to-skin care.

Breast Pump Suction Patterns

The ability of breast pumps to remove milk depends primarily on the magnitude and rate of vacuum suction,⁴⁵ with stronger suction levels resulting in higher milk yields⁴⁶ and repetitive vacuum suction cycling triggering an MER.⁴⁶ Currently, 2 BPSPs are available that adapt the cycling rate of vacuum suction to elicit additional MERs including the Standard BPSP (S-BPSP, Standard 2.0, Medela, Baar, Switzerland) and irregular BPSP (I-BPSP, Preemie+ card, Medela, Baar, Switzerland). The S-BPSP is a 2-phased suction pattern with rates of 120 suck cycles per minute for up to 2 minutes during the MER stimulation phase and rates of 60 per minute during the expression phase. The biphasic pattern of the S-BPSP resembles the healthy, term breastfeeding infant's suckling pattern before (stimulation phase) and after an MER (expression phase). The breastfeeding infant feeds at the breast, with pauses and suck bursts of nutritive likely resulting in milk transfer and nonnutritive suck patterns likely resulting in negligible milk transfer with a faster suck rate during nonnutritive sucking.⁴⁷ Before each MER, breastfeeding infants exhibit more nonnutritive sucking, as opposed to after an MER when the suck rate becomes slower with more time spent in nutritive sucking.⁴⁷ The I-BPSP operates at rates of 60, 90, or 120 suck cycles per minute, with random pauses seeking to replicate the preterm infant suckling behavior, which differs from breastfeeding infant's more biphasic suck pattern.

This review found a single study that explored variations in BPSPs as a method to improve milk production. Post et al³⁹ assigned mothers of term (n = 19), late preterm (n = 44), and preterm infants (n = 67) to use I-BPSP or S-BPSP prior to the onset of secretory activation based upon which suction pattern was available at the start of their first expression. After adjustment for GA, they found the I-BPSP was associated with an earlier onset of secretory activation (3.3 vs 4.5 days; P < .001) in mothers of preterm and late preterm infants and higher daily milk volume (P < .001) for 14 days in all 3 GA categories.³⁹ Although the rate variation in suck cycles with I-BPSPs more closely resembles preterm infant feeding behavior, I-BPSPs may be associated with an earlier onset of secretory activation and later adequate milk production in pump-dependent mothers of any GA infant.

Breast Massage and Application of Warm Compresses

Two studies explored the effect of breast massage and/or application of warm compresses to the breast on milk production.^28,42 Breast massage involves application of gentle pressure in circular, kneading, stroking, and compression motions directed from the back of each breast toward the nipple to assist in draining milk from the breast.²⁸ Warm compresses applied to the breast before an expression session may increase breast blood flow, elicit an MER, and improve efficiency of milk removal.⁴⁸ Divya et al²⁸ found milk production was higher when 30 mothers of infants admitted to the NICU used breast massage combined with warm compresses during hand expression over 3 consecutive expression sessions between days 3 and 8 postpartum compared with 3 previous consecutive expression sessions without the use of these complementary therapies (7.33 vs 15.56 mL; P = .001). Similarly, Yigit et al⁴² randomized 39 mothers' right and left breast to unilaterally have a warm compress applied for 20 minutes before 6 expression sessions (2 daily expressions for 3 days) and found the warmed breast produced higher milk volumes (P < .001). While this review finds limited support for breast massage and warm compresses as strategies to increase milk volume, further research is warranted.

Environment and Relaxation Therapies

Stress and anxiety are known to affect milk production by negatively influencing the MER.⁴³ An environment that reduces stress and anxiety and the use of relaxation therapies such as music may increase milk production by stimulating and increasing the number of MERs.^20,49 One study examined the effect of expression location and mothers' proximity to their infant on milk production over 10 days and found mothers (n = 26) expressed more milk when at their infant's bedside compared with at home (101.2 vs 97.4 mL; P = .046).¹⁰ Yet, no differences were found between expressing at home versus in the hospital while not at their infant's bedside.¹⁰

Results of 3 studies suggest exposure to music therapy may increase milk production.^20,25,32 In a small study conducted over 4 days,³² 29 mothers of infants less than 34 weeks' GA listened to 30 minutes of music therapy before and during 4 out of 8 expression sessions. Researchers found increased milk volume during the sessions when mothers listened to music (7.12 vs 6.68 mL; P = .033), but differences were less than 1 mL, which may not be clinically significant. In the second study, no differences in milk volume were found when mothers of NICU infants (28-34 weeks' GA) were randomized to listen to 15 minutes of music during 2 expression sessions over a 3-day period. However, they did produce more milk during the final study day (23.1 vs 12.3 mL; P = .001).²⁵ Both studies may be limited by the small number of intervention sessions; hence, results should be interpreted with caution. Lastly, researchers randomized 162 mothers of infants less than 38 weeks' GA admitted to the NICU to receive guided relaxation, guided relaxation with lullabies and infant images, guided relaxation with lullabies, or no intervention (control group) while expressing.²⁰ Each of the experimental groups produced more milk than the control group from day 2 (64.8, P < .001; 79.9, P < .001; 65.6, P < .001; vs 35.2 mL) to day 14 (591.4, 1028.0, 861.7 vs 318.2 mL; P < .001), respectively, with mothers who received guided relaxation with lullabies and infant images producing the most milk.²⁰ Interestingly, mothers randomized to receive solely guided relaxation produced more milk than mothers experiencing a combination of guided relaxation with lullaby music. Although limited, evidence suggests music and/or guided imagery therapy may increase milk volume and further studies are needed to explore the effect of these low-cost and convenient interventions on milk production.

Skin-to-Skin Care

Skin-to-skin care (STS) is defined as an infant clad only in a diaper being held directly on their mother's chest¹⁰ and may increase milk production by lowering maternal stress and anxiety in addition to increasing oxytocin levels, which may increase the number of MER occurrences.⁵⁰ Four studies investigated whether STS was associated with milk production. Acuña-Muga et al¹⁰ found milk production increased both during and immediately following mothers engaging in STS compared with expressing at their infants' bedside without STS (107.7 vs 96.7 mL; P = .003, and 117.7 vs 96.7 mL; P < .001, respectively) throughout the 10-day study. Hill and Aldag³⁰ reported that a single episode of STS during week 1 was positively predictive of milk volume through week 6 (r_s= 0.33, P < .01). Likewise, Fewtrell et al²⁶ found the number of episodes of STS care during the first 10 days following delivery was positively predictive of day 10 milk volume in mothers of infants less than 34 weeks' GA (r = 0.34, P = .007) but did not report the number of STS episodes. In a large cohort study (n = 124),³⁵ researchers found the total time a mother spent in STS positively influenced 24-hour milk production at 2, 4, 6, 8, and 10 weeks postpartum (P = .02) and whether or not mothers continued lactating for 10 weeks (odds ratio = 1.05, P = .048), yet total time spent in STS was not reported. However, due to the high attrition rate (47%), results may represent mothers more motivated to continue expressing milk. Based on 4 studies, STS may have a positive effect on milk volume; however, further research is needed to explore best practices for implementation, such as timing and number of episodes.

IMPLICATIONS FOR RESEARCH AND CLINICAL PRACTICE

Mothers of infants admitted to the NICU must rely on milk expression to establish and maintain an adequate milk production for purposes of lactation for high-risk infants. Volume of milk obtained during expression may be influenced by multiple potentially modifiable factors including timing and frequency of expression, expression methods, and complementary expression strategies such as breast massage. Results of this review also suggest simultaneous expression using a hospital-grade electric breast pump at least 5 times a day with no longer than 4 to 7 hours between sessions may be the best method to facilitate milk production in mothers of critically ill infants. However, use of hand expression combined with an electric breast pump until the onset of secretory activation, then subsequently expressing with an electric breast pump adding hands-on-pumping to the electric breast pump expression, may increase breast emptying. It is possible that hands-on-pumping may increase oxytocin release due to the combination of tactile stimulation and breast compression from hand expression and increased intramammary and intraductal pressure from breast pump cycling thus increasing milk removal.³⁶ Colostrum, which is viscous, may be more effectively removed using hand expression than with a breast pump. An improvement in effectiveness of milk removal may result in greater milk production the first weeks postpartum. In addition, complementary strategies including I-BPSP, breast massage, and warm compresses may increase the number of MERs per expression session, thereby increasing milk production. Music and/or visual imagery, as well as STS care, may positively influence milk production, but further research including adequately powered RCTs is needed. Although complementary strategies may be cost-effective and require little maternal effort, qualitative studies are needed to understand how mothers experience the use of these complementary strategies.^16,17 However, healthcare professionals should consider instructing mothers to include breast massage, warm compresses, and music to their expression routine, as well as implementing policies and protocols that support and encourage STS care.

Further research is needed to explore practices to support initiation of expression within 6 hours following delivery focusing on the first 3 to 6 hours as the optimal of time to initiate. Since pump dependency may be a risk factor for decreased milk supply, research is needed in pump-dependent mothers who deliver infants of all GAs. In addition, further exploration of other modifiable expression factors including frequency and duration of expression to increase milk production is needed. Given that volume of milk produced may vary based on the time of day, future research should focus on assessing milk volume over 24 hours.

A rigorous search strategy was used to reduce publication and selection bias to identify relevant studies; however, this state-of-the-science review has limitations. Although the influence of expression factors on milk production is likely multifactorial in pump-dependent mothers, this review was limited to the expression factors reviewed. The reviewed studies often included small samples that described large individual variations in milk volume, which may have limited the effect of the modifiable expression factor on milk production. Moreover, longitudinal studies were limited by missing data from attrition of study participants over time. Finally, milk volume was primarily determined by maternal self-report, which is subject to recall bias.

CONCLUSION

This state of the science critically reviewed the evidence from 26 articles on expression factors that may affect MOM production in pump-dependent mothers of critically ill infants admitted to the NICU. Establishment and maintenance of an adequate milk volume is a global concern for mothers of infants admitted to the NICU and requires evidence-based strategies that can be universally applied to increase milk volume. Multidisciplinary approaches are likely necessary to understand the complexity of pump dependency and expression factors that may affect milk production.

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What we know:	The amount of mother's own milk an infant receives while admitted to the neonatal intensive care unit has been associated with lower hospitalization costs and improved infant health outcomes. Mothers of infants admitted to the neonatal intensive care unit must rely on milk expression to establish and maintain an adequate milk production. Long-term milk production is strongly associated with production in the first few days after delivery.
What needs to be studied:	Targeted interventions to implement early initiation of expression and optimal frequency of expressions. Amount and frequency of modifiable factors that may increase milk volume to include skin-to-skin care and combining hand techniques with simultaneous breast pump expression. How to apply interventions to increase milk volume for pumpdependent mothers.
What we can do today:	Assist pump-dependent mothers with early initiation, and frequent milk removal. Instruct mothers on complementary strategies that may increase milk volume to include breast massage, warm compresses, music, hand expression, and skin-to-skin care to their expression routine.