Non-Pharmacologic Factors Affecting Milk Production in Pump Dependent Mothers of Critically Ill Infants: State of 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 non-pharmacologic 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 was extracted by three 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 3–6 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:

Health care 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.

Introduction

The American Academy of Pediatrics recommends all infants receive exclusive human milk feedings for the first six months including donor human milk (DHM) for preterm infants when mother’s own milk (MOM) is not available.¹ The use of MOM compared to 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 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 has risen 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 gestational ages (GA).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 10mL/kg/d 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 suggests 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 processes¹³ suggesting prolonged milk production is influenced by early and effective milk removal.¹⁴ Hill et al.¹⁵ reported milk volume in mothers of preterm infants declined from weeks 3 through 6 postpartum, compared to 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 and Aldag¹⁸ 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 three 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, breastmilk, 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 of 2005 to December of 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 (RCT) 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 (MMB) screened the titles and/or abstracts based on inclusion and exclusion criteria, then full text articles were obtained for further review. Two secondary reviewers (LCI, LAP) 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 flow diagram of study selection.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. doi: 10.1136/bmj.n71.

Results

This literature review yielded 26 studies that met the inclusion and exclusion criteria for critical analysis. Six studies were RCTs^{20,21,22,23,24,25} of which three were pilot studies. One²⁶ was a secondary analyses of a 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 & location	Study design and purpose	Methods and sample population
Acuña-Muga et al., 201410 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 weeks 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 days
Bishara et al., 200932 Canada	Prospective descriptive. To describe foremilk, hindmilk and total MV in relation to expression factors.	24 mothers of infants <28 weeks GA and 21–30 days old who expressed ≥4x/day and whose MV exceeded their infants’ needs by 20%. Mothers recorded MV for 24 hours.
Divya et al., 201645 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 days postpartum. MV was measured using a measuring cup and compared with MV from 3 session with no massage/warm compresses.
Fewtrell et al., 201626 United Kingdom	Secondary analysis To investigate factors predicting MV during the first 10 days postpartum and during the infant’s entire hospital stay.	62 mothers of infants 24–34 weeks GA recorded STS episodes, MV (determined by weight), expression session duration, and whether simultaneous or sequential expression was used in a diary for 10 days postpartum. 47 mothers recorded information until infant discharge.
Henderson et al., 200834 Australia	Prospective cohort. To explore 24-hour MV over 10 days.	50 mothers of infants 24.2 to 33.7 weeks GA recorded milk weight, frequency, and duration of expressions in a diary for 10 days after delivery.
Hill & Aldag, 200527 USA	Longitudinal cohort. To determine if day 4 expression frequency and MV predicted week 6 MV adequacy.	81 mothers of infants <1500 g and ≤31 weeks GA recorded MV and time of expressions in a logbook. Information regarding STS during day 1–7 was obtained via questionnaire.
Hill et al., 200515 USA	Observational prospective cohort. To determine whether MV week 1 through week 6 differs by GA.	Mothers of infants ≤31 weeks GA (n=95) and mothers of healthy breastfeeding term infants (n=98) recorded MV and expression or breastfeeding duration for 6 weeks.
Hill et al.,14 2009 USA	Observational cohort. To compare MV, expression frequency and hormone levels between mothers of preterm and term infants.	Pump-dependent mothers of infants ≤31 weeks GA (n=95) and breastfeeding mothers of term infants ≥37 weeks GA (n=98) recorded MV and expression frequency and/or breastfeeding in a logbook for 6 weeks.
Hoban et al., 201835 USA	Pilot observational. To describe relationships between biomarkers, MV, and expression frequency for days 1–14 postpartum.	16 mothers of infants <33 weeks GA recorded expression duration in a pumping log for 14 days, MV volume was determined by weighing vials of milk (by nursing staff).
Jayamala et al., 201549 India	Quasi-experimental. To evaluate the effect of music therapy on MV.	30 mothers of infants <34 weeks GA listened to music before and during 4 of 8 expression sessions over 4 days. MV measured using vial gradations.
Keith et al., 201220 USA	Pilot RCT. To explore the effect of 3 musical interventions on MV.	162 mothers of infants <38 weeks GA were randomized to 1 of 4 interventions (guided relaxation & lullabies; infant images, guided relaxation & lullabies; guided relaxation; or standard care). Mothers recorded MV for 14 days.
Köroğlu et al., 201740 Turkey	Descriptive quasi-experimental. To compare sequential vs simultaneous expression on MV.	Mothers (n=35) of infants 25–38 weeks GA self-selected to either simultaneous or sequential expression. Recorded MV, frequency and expression duration for 10 days.
Lai et al., 202037 Australia	Observational cohort. To determine the effect of expression regimes on MV during early lactation.	25 mothers of infants <34 weeks GA recorded expression session duration and MV on day 10 and days 15–20 postpartum. MV was determined by weight.
Lau et al., 200736 USA	Observational cohort. To determine associations between MV, STS, and lactation duration.	124 mothers of infants 26–29 weeks GA recorded daily MV and expression frequency over 10 weeks postpartum and information on STS during infant hospitalization.
Lussier et al., 201521 USA	Pilot RCT. To compare MV using HE vs. EE days 1–7 and 28 days post-delivery.	40 mothers (HE n=12, EE n=14) of infants ≤1,500 g and ≤32 weeks GA recorded MV, time of expression, and method of expression (HE or EE) in a logbook.
Morton et al., 200933 USA	Observational prospective cohort. To determine whether HE of colostrum and hands-on-pumping of mature milk affects MV over 8 weeks postpartum.	67 Mothers of infants <1500g and <31 weeks GA recorded time of expression and MV for 8 weeks. A subset of mothers (n=42) began hands-on-pumping at 20.6±9.6 days into the study.
Murase et al., 201429 Japan	Retrospective chart review. To examine MV days 1–4 and mother’s own milk at NICU discharge.	Expression frequency, time to first expression and MV for the first 4 days after delivery was extracted from the medical records of 87 mothers of infants <32 weeks GA.
Parker et al., 201222 USA	Pilot RCT. To compare MV between mothers who initiated expression ≤1h vs. 1–6h following delivery over 6 weeks.	Mothers of infants <32 weeks GA and <1500g were randomized to initiate expression <1h (n=10) or 1–6h (n=10) after delivery. MV was measured by weight on day 1–7, and weekly for 6 weeks.
Parker et al., 201528 USA	Pilot prospective cohort. To determine the effect of time to initiation of expression on time to SA and MV over 6 weeks.	40 Mothers of infants <1500 g and <32 weeks GA initiated expression <6 h (n=20) or >6h (n=20) after delivery. MV was measured by weight on day 1–7 and weekly for 6 weeks.
Parker et al., 202024 USA	RCT. To determine the effect of time to expression initiation on time to onset of SA and MV over 6 weeks.	180 mothers of infants ≤1500 g and ≤32 weeks GA were randomized to initiate expression ≤1h (n=58), >1–3h (n=62), or >3–6hours (n=60). MV was measured by weight on days 1–7 and weekly for 6 weeks.
Post et al., 201644 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 a S-BPSP (n=64) or I-BPSP (n=66) until SA. Mothers recorded MV days 1–14.
Ru et al., 202030 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 <1,500g and <32 weeks GA recorded expression frequency and duration and MV by weight in a diary on days 1–14, day 21, 28, 35, and 42 postpartum.
Slusher et al., 200723 Kenya /Nigeria	RCT. To compare MV using electric BP, non-electric pedal BP, and HE.	65 mothers of infants 26–40 weeks 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 bottle for 10 days.
Slusher et al., 201239 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 non-electric manual BP (n=59), or HE (n=47). MV was measured using a graduated scale on bottles for 7 days.
Varişoğlu, et al., 202025 Turkey	RCT. To compare the effect of listening to music on MV over 4 days.	40 mothers of infants 28–34 weeks GA were randomized to listen to music (n=20) or no music (n=20) during 2 expression sessions a day for 3 days.
Yigit et al., 201246 Turkey	Quasi-experimental. To investigate the effect of warm compresses on MV	39 mothers of infants <21 days old were randomized to apply a warm compress for 20 minutes to one breast before 2 expressions a day for 3 days. MV was measured by graduated scale on bottle.

Abbreviations: BP, breast pump; GA, gestational age; EE, electric pump expression; 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 birthweight (VLBW, <1500 grams) 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 (1mL = 1gram) 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 (Year)	Key Findings
Timing of initiation of first expression
Hill & Aldag27 (2005)	Earlier time to initial expression (rs=− 0.22, p=.05), was positively predictive of milk adequacy (defined as ≥500 mL/day) at week 6.
Murase et al.29 (2014)	Median time to first expression was 20h (8–29) postpartum with 36% of mothers beginning expression after 24 hours postpartum. Milk expression initiation <6 hours was not associated with low milk volume on day 4 (<153mL).
Ru et al.30 (2020)	MV on days 7, 14, and 42 was similar between mothers initiating expression <6h and >6h. (7.6h range 4.6–10.3).
Parker et al.22 (2012)	Mothers who began milk expression <1h after birth had greater MV during the 1st week postpartum (1374.7 vs. 608.1 mL; p=.05) and at week 3 (p<.01) than those who began expressing 1 to 6h after birth and had an earlier onset of SA (80.4h vs. 136.8h; p=.03).
Parker et al.28 (2015)	Initiation of expression <6 h after delivery was associated with greater MV on day 6 (p=.001) and 7 (p=.006). Initiation of expression <6h was associated with greater MV during days 1–7 (p=.076) and at 6 weeks (p=.05) but was not statistically significant. Expression initiation <1h after delivery (n=10) was associated with greater MV compared to initiation 1–6h (n=10) or >6h (n=20) at day 7 (306.2, 244.0–384.3 vs. 180.7, 80.8–253.2, vs. 125.7, 65.3–192.7; p=.005) at week 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 week 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 al.24 (2020)	Initiation of expression 3–6 hours after delivery was associated with increased MV days 1–3 (p=.031) and at 6 weeks (p=.045) compared to initiation at <1h but was similar to initiation between 1–3h.
Breast Expression Frequency
Bishara et al.32 (2009)	Total MV did not correlate with milk expression frequency or longest time between expressions.
Hill et al.15 (2005)	Mothers of preterm infants expressed fewer times/day than mothers of term infants (either expressed or breastfed) across all weeks (p<.001).
Hill et al.14 (2009)	MV was positively related to expression frequency in mothers of both preterm and term infants (p<.001; p<.001 respectively).
Fewtrell et al.26 (2016)	MV was positively predicted by greater number of expressions during the first 10 days (r=0.43 p=.001) and throughout the infant’s hospital stay (r=0.36, p=.01).
Lussier et al.21 (2015)	Daily expression frequency between groups was similar. Daily MV was positively associated with daily expression frequency (coefficient 25, 95% CI 14, 37, p<.001), with each expression session adding an adjusted 25 mL to daily MV.
Hill & Aldag27 (2005)	Greater day 4 expression frequency (rs=0.32, p<.01) was positively predictive of milk adequacy (defined as ≥500 mL/day) at week 6.
Murase et al.29 (2014)	≥4 expressions Day 2 was associated with MV (median ≥153 mL) on day 4 (p=.02).
Lau et al.36 (2007)	Daily expression frequency (4.6±1.3 to 5.7±1.2 times/day) was positively correlated with 24-hour MV (p=001).
Morton et al.33 (2009)	HE >5 times/day vs. <2 times/day or 2 to 5 times/day on days 1–3 postpartum was associated with greater MV during week 2 (710±402 vs. 392±196 mL, p < .005; 448 ±318 mL, p=.023, respectively) and greater MV on day 14 but not at week 8. MV at 8 weeks was positively associated with BP expression frequency (p=.002), expression session duration (p=.033) and longest interval between expression sessions (p<.01). ≥7 expressions/day was associated with higher MV compared to <7 times/day at 2 weeks (p=.030) but not 8 weeks (p=.170).
Hoban et al.35 (2018)	Mother who achieved MV >500 mL/day by day 14 compared with mothers who did not had increased expression frequency days 1–5 (p<.001) and days 1–14 (p=.03). Mothers who expressed ≥5 vs. <5 times/day were more likely to achieve >500 mL/day by day 14 (p=.01).
Lai et al.37 (2020)	MV was greater on days 10 and 15–20 with 6 vs. 3 expressions/day (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/day (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/day.
Henderson et al.34 (2008)	Over 10 days, 24-hour MV was positively associated with expression frequency (p<.001). Mothers who expressed ≥6 times/day vs. <6 times/day produced greater MV.
Ru et al.30 (2020)	Expression frequency of ≥6 vs. <6 times/day was associated with greater MV on day 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 one 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).^{22,24,27,28,29,30} While one small pilot RCT suggests initiation within one 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 one hour.²⁴ In this study, mothers who initiated expression 3 – 6 hours after delivery produced more milk over the first 6 weeks compared to those who initiated at less than 1 hour (p = .045). However, mothers who initiated expression 3 – 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 study³⁰ reported no differences in milk production on postpartum days 7, 14, or 42 between mothers who initiated expression within 6 hours of delivery compared to those who initiated more than 6 hours postpartum. In mothers who initiated expression more than 6 hours postpartum, 43% initiated 6–12 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=81,²⁷ n=87²⁹) 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 two observational studies support earlier expression initiation, furthermore, one observational study and two 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.³¹ 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 al.,¹⁵ found in their sentinel study that mothers of preterm infants expressed less frequently than mothers of term breastfeeding infants over 6 weeks (5.7 to 6.05 vs. 8.0 to 8.9 times/day; p<.001) and were 2.8 times more likely to produce milk volume <500 mL/day by week 6. However, Bishara et al.³² 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 study³² included a small sample size, was conducted over a short time 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 27.6–30.6 weeks gestation, Murase et al.²⁹ 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 to 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 (rs = 0.32; p < .01).²⁷

Expression frequency prior to the onset of secretory activation may be associated with milk production during the first few weeks following delivery. Morton et al.,³³ 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 to those who expressed less 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 two weeks (622 vs. 402 mL; p = .03) but not at eight 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 ^30,34,35 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 al.³⁶ found a positive correlation (p = .001) between daily expression frequency (4.6 to 5.7 times/day) and 24-hour milk volume at week 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 study³⁷ 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 15–20 than expressing 3 times/day (p = .006). Likewise, expressing 7 times/day was associated with greater milk production per expression compared to 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 – 10 times per day during the first 28 days postpartum and that each additional expression was associated with a daily milk volume increase of 25mL (p < .001).²¹ Based upon the results of thirteen 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. A milk ejection reflex is a neuro-hormonal reflex stimulated by oxytocin released from the posterior pituitary leading to alveolar myoepithelial cell contracture and milk release.³¹ 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.^31,38 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.³¹

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.³³ 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 multi-step 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.³³ Two main types of breast pumps are available for use including manual which 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 seven 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 (Year)	Key Findings
Breast pump versus hand expression
Lussier et al.21 (2015)	Exclusive EE compared to exclusive HE over the first week was associated with greater daily MV (p<.05) and cumulative MV (1,371 vs. 456 mL; p=.003) days 1–7 postpartum and higher MV of 119 mL/day (coefficient −119, 95% CI: −175, −63, p<.001) and cumulative MV days 1–28 (13,639 [3,020, 17,770] vs. 7,208 mL [4,240, 14,279].
Slusher et al.23 (2007)	Use of a double electric BP was associated with greater daily MV over 10 days than HE (578 vs. 323 mL; p<0.01). Similar MV was obtained between an electric BP and pedal pump (463 mL) and between pedal pump and HE.
Slusher et al.39 (2012)	Mothers who expressed using a double electric BP had greater daily MV over 7 days than mothers using HE (647 vs. 434 mL; p<.01), but similar to those using a single non-electric manual BP (520mL). Similar MV was obtained between mothers expressing with single non-electric manual BP and HE.
Combining the use of breast pumps with hand expression or hands-on-pumping
Morton et al.33 (2009)	Hands-on-pumping was associated with increased daily MV 583±383 to 863±506 mL; p<.003).
Simultaneous versus sequential expression
Fewtrell et al.26 (2016)	MV was positively predicted by simultaneous vs. sequential expression (109 mL/day 95%CI 31–186, p=.007) on day 1–10 (288 [168, 386] vs. 147mL/day [78, 275]) and during the infant’s hospital stay (218 mL/day 95% CI 80 to 356, p=.003; 561 (202, 708) vs 220 (112, 349) mL/day).
Köroğlu et al.40 (2017)	Mothers who expressed using simultaneous vs. sequential expression achieved similar MV in a shorter amount of time (11.57 – 15.62 minutes vs.18.16 – 20 minutes.

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 two separate studies, Slusher and colleagues compared the effect of four expression methods (hand expression, electric breast pump, manual breast pump, and pedal pump) on milk volume. In the first study, 65 mothers of infants 26–40 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 seven 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.³⁹ Similarly, Lussier et al.²¹ found mothers who used an electric pump produced more milk than those who performed hand expression over the first week (cumulative median 1,371 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 to those using an electric pump during the first week (7,208 vs. 13,639 mL) which may be clinically important.²¹ Together these three studies suggest greater milk volume may be obtained with 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 al.³³ found those who used hand expression greater than 5 times per day combined with breast pumping during the first three days postpartum compared to those who did not hand express or did so less 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 3–4 weeks postpartum, milk volume was increased at 8 weeks postpartum when compared to 3 days prior to initiation of hands-on-pumping (583 vs. 863 mL; p < .003).³³ Evidence from only one observational study supports combining hand expression with an electric breast pump during the first three 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.^26,40 One small observational study⁴⁰ 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, a RCT (n=62) reported simultaneous compared to sequential expression resulted in greater daily milk volume over 10 days (288 vs. 147mL/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 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 (Year)	Key Findings
Breast pump suction patterns
Post et al.44 (2016)	The I-BPSP group had greater MV day 3–14, (p<.001), experienced an earlier onset of SA (3.3±0.6 vs. 4.5±2.1 days; p<.001) and reached a MV of > 500 mL/day earlier (7.7±2.4 vs. 9.5±3.0 days; p<.01).
Breast massage and application of warm compresses
Divya et al.45 (2016)	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 al.46 (2012)	During each of the 6 expression sessions, the warm compress breast produced greater MV (p<.001). Differences were greatest on the 5th of 6 expressions on day 3 (47.02±23.01 vs. 33.15±19.98 mL; p<.001).
Environment and relaxation therapies
Acuña-Muga et al.10 (2014)	The first expression of the day had the greatest MV (difference, 38.5 mL; 95% CI, 33.1–44.0 mL; p<.001) and when expression occurred in proximity vs. far from infant (adjusted difference, 3.82 mL; 95% CI, 0.05–7.58 mL; p=.046) or when expressing at the infant’s bedside vs at home (101.2 mL, 95% CL 88.1–114.3 vs. 97.4 mL, 95% CL, 84.3–110.5; p=.046).
Keith et al.20 (2012)	Mothers in the 3 experimental groups produced more milk over the 14 days than the control group (p<.001).
Jayamala et al.49 (2015)	Mothers produced greater MV during the 4 music vs. 4 no music expression sessions (7.12 vs. 6.68 mL; p=.033).
Varişoğlu et al.25 (2020)	MV was greater in the music group compared on the third to fourth day (23.1±14.1 vs. 12.3±11.8 mL; p=.001).
Skin-to-skin care
Acuña-Muga et al.10 (2014)	MV was greater when mothers expressed during STS vs. at their infant’s bedside (difference, 11 mL; 95% CI, 4.8–17.2; Bonferroni adjusted p=.003) and after STS vs. at their infant’s bedside (difference, 21 mL; 95% CI, 9.5–32.6; 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 al.26 (2016)	Positive predictors of MV included more STS episodes on day 1–10 and during the infant’s hospitalization (r=0.34 p=.007; r= 0.26 p=.08; respectively).
Hill & Aldag27 (2005)	STS during week 1 (rs=0.33, p<.01) was positively predictive of milk adequacy (defined as ≥500 mL/day) at week 6.
Lau et al.36 (2007)	Time in STS was positively associated with 24-hour MV (p=.020) and whether or not mothers continued expressing until infant discharge. (p=.048, OR=1.05 95% CI 1.00, 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; 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,⁴¹ with stronger suction levels resulting in higher milk yields⁴² and repetitive vacuum suction cycling triggering a MER.⁴² Currently, two breast pump suction patterns (BPSP) are available that adapt the cycling rate of vacuum suction to illicit 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 two-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 a MER (expression phase). The breastfeeding infant feeds at the breast with pauses and suck bursts of nutritive likely resulting in milk transfer and non-nutritive suck patterns likely resulting in negligible milk transfer with a faster suck rate during non-nutritive sucking.⁴³ Before each MER, breastfeeding infants exhibit more non-nutritive sucking, as opposed to after a MER when the suck rate becomes slower with more time spent in nutritive sucking.⁴³ 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 breast pump suction patterns as a method to improve milk production. Post et al.⁴⁴ 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 three GA categories.⁴⁴ 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.^45,46 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.⁴⁵ Warm compresses applied to the breast before an expression session may increase breast blood flow, illicit a MER, and improve efficiency of milk removal.⁴⁷ Divya et al.⁴⁵ 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 to 8 postpartum compared to 3 previous consecutive expressions sessions without the use of these complementary therapies (7.33 vs. 15.56 mL; p = .001). Similarly, Yigit et al.⁴⁶ randomized 39 mother’s 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.³¹ 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.^20,48 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 to 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 three studies suggest exposure to music therapy may increase milk production.^20,25,49 In a small study conducted over four days,⁴⁹ 29 mothers of infants <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 1mL 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 three day period. However, they did produce more milk during the final study day (23.1 vs. 12.3mL; 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 al.¹⁰ found milk production increased both during and immediately following mothers engaging in STS compared to 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 Aldag²⁷ 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 al.²⁶ 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),³⁶ 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 (OR=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 four 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.³³ 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 are 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, health care 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 gestational ages. 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 multi-factorial 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. Multi-disciplinary approaches are likely necessary to understand the complexity of pump dependency and expression factors that may affect milk production.

Acronyms and Abbreviations:

BFHI

Baby-Friendly Hospital Initiative

BP

breast pump

BPSP

breast pump suction pattern

CI

confidence interval

DHM

donor human milk

EE

electric breast pump expression

GA

gestational age

HE

hand expression

I-BPSP

irregular breast pump suction pattern

MER

milk ejection reflex

MV

milk volume

mL

milliliters

MOM

mother’s own milk

NICU

neonatal intensive care unit

RCT

randomized control trial

SA

secretory activation

STS

skin-to-skin care

S-BPSP

standard breast pump suction pattern

VLBW

very low birth weight