image1.jpg

Journal of Midwifery &Women’s Health www.jmwh.org

Review

CEUBreastfeeding Outcomes After Oxytocin Use During

Childbirth: An Integrative Review Elise N. Erickson, CNM, MS, Cathy L. Emeis, CNM, PhD

Introduction:Despite widespread use of exogenous synthetic oxytocin during the birth process, few studies have examined the effect of this drug

on breastfeeding. Based on neuroscience research, endogenous oxytocin may be altered or manipulated by exogenous administration or by block-

ing normal function of the hormone or receptor. Women commonly cite insufficient milk production as their reason for early supplementation,

jeopardizing breastfeeding goals. Researchers need to consider the role of birth-related medications and interventions on the production of milk.

This article examines the literature on the role of exogenous oxytocin on breastfeeding in humans.

Methods: Using the method described by Whittemore and Knafl, this integrative review of literature included broad search criteria within the

PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, and Scopus databases. Studies published in English

associating a breastfeeding outcome in relation to oxytocin use during the birth process were included. Twenty-six studies from 1978 to 2015 met

the criteria.

Results: Studies were analyzed according to the purpose of the research, measures and methods used, results, and confounding variables. The

26 studies reported 34 measures of breastfeeding. Outcomes included initiation and duration of breastfeeding, infant behavior, and physiologic

markers of lactation. Timing of administration of oxytocin varied. Some studies reported on low-risk birth, while others included higher-risk ex-

periences. Fifty percent of the results (17 of 34measures) demonstrated an association between exogenous oxytocin and less optimal breastfeeding

outcomes, while 8 of 34 measures (23%) reported no association. The remaining 9 measures (26%) had mixed findings. Breastfeeding intentions,

parity, birth setting, obstetric risk, and indications for oxytocin use were inconsistently controlled among the studies.

Discussion: Research on breastfeeding and lactation following exogenous oxytocin exposure is limited by few studies and heterogeneousmethods.

Despite the limitations, researchers and clinicians may benefit from awareness of this body of literature. Continued investigation is recommended

given the prevalence of oxytocin use in clinical practice.

J Midwifery Womens Health 2017;62:397–417 c© 2017 by the American College of Nurse-Midwives.

Keywords: active management third-stage labor, breastfeeding, drug effects, lactation, labor (induced), labor (obstetric), labor stage (third),

oxytocin

INTRODUCTION

While increasing numbers of women are breastfeeding their newborns at birth, the ability to maintain breastfeeding may be affected by factors contributing to maternal milk pro- duction. This is reflected by the Centers for Disease Con- trol and Prevention (CDC) 2016 Breastfeeding Report Card, which shows that while 81.1% of women initiate breastfeed- ing after birth, only 44.4% of women are still exclusively breastfeeding at 3 months, falling to 22.3% of infants by the 6-month target.1 Common reasons for early cessation of ex- clusive or any breastfeeding is the perception of insufficient milk supply2,3 and the early introduction of formula.4,5 There- fore, factors that may influence physiologic milk production are compelling targets for translational research.

Understanding possible causes of suboptimal breastfeed- ing may have implications for improving maternal and in- fant health. Infants receiving formula or solid foods before 6 months of age are at increased risk for acute and chronic illnesses, as well as sudden infant death syndrome.6 The number of infant deaths potentially preventable by meeting breastfeeding goals are estimated upwards of 700 annually.7,8

Furthermore, a growing body of literature is examining the

Address correspondence to Elise N. Erickson, CNM, MS, Oregon Health & Science University, School of Nursing, 3455 SE US Veterans Hospital Rd, Portland, OR 97239-2941. E-mail: [email protected]

long-term effect of breastfeeding on maternal health. Women who have no breastfeeding history have poorer indices of car- diovascular health in later life.9 Another study used a simula- tionmodel to estimate the impact of suboptimal breastfeeding on many maternal health outcomes, reporting a potential an- nual excessmortality of 3340 deaths andmore than $14 billion in costs in the United States due to premature death.7

Milk production and successful breastfeeding require oxytocin-driven neuroendocrine pathways that are primed by pregnancy and the process of childbirth.10 Endogenous oxytocin function is essential for onset of lactation and milk ejection in mammals.11 Manipulation of oxytocin in experi- mental animal models can lead to deficits in lactation, ma- ternal behavior, and abnormal behavioral development of offspring.12,13 Oxytocin is commonly administered inmodern maternity care for labor augmentation, induction of labor,14

and to minimize or treat uterine bleeding in the third stage of labor.15 There is evidence that exogenous oxytocin can pass through the placenta and into fetal circulation.16 Therefore, depending on the timing of administration, this synthetic hor- mone and neurotransmitter could affect neonates as well as women.

The significance of these questions relate to the extensive use of oxytocin in practice. Estimates of induction of labor, typically involving exogenous oxytocin, range from 23% to 29% of births17,18 but may be in the range of 31% to 42% in

1526-9523/09/$36.00 doi:10.1111/jmwh.12601 c© 2017 by the American College of Nurse-Midwives 397

✦ Oxytocin administration during childbirth is widespread; few studies have investigated the effects of this on breastfeeding, and most of these have not directly studied the relationship.

✦ The effect of exogenous oxytocin on breastfeeding has been measured through infant breastfeeding behavior, physiologic lactation, maternal initiation, and duration or exclusivity of breastfeeding.

✦ While oxytocin administration has an important role in modern maternity care, potential effects on lactation should be explored more, as the research on breastfeeding outcomes is incomplete.

some settings, based onUSdata.19,20 Amongwomenwho start labor spontaneously, augmentation of labor with oxytocin due to slow progress is also frequent,20 though exact national rates are not published. Epidural analgesia is also associated with induced and augmented labor, with more than 75% of women using epidural analgesia undergoing induction or augmenta- tion, according to 2008 CDC data.21 During cesarean birth, accounting for 32.7% of births,18 oxytocin is administered af- ter extracting the placenta to slow bleeding.15 Finally, to help minimize bleeding, the World Health Organization (WHO) promotes prophylactic administration of oxytocin as the stan- dard of care following vaginal birth.15 It is also a mainstay treatment for postpartum hemorrhage.

Despite widespread use of oxytocin and the importance of the physiology of oxytocin for successful lactation, clinical studies have rarely explored long-term effects on women and infants, such as breastfeeding outcomes.22,23 The purpose of this integrative review is to understand 1) what breastfeeding outcomes (maternal or infant) have been reported following any clinical oxytocin administration and 2) any patterns in the published results to better inform future research.

METHODS

An integrative approach described by Whittemore and Knafl informed the procedure for this review, as a preliminary litera- ture search revealed significant heterogeneity in methods and outcomes among relevant studies.24 We were unable to iden- tify articles synthesizing the body of literature regarding oxy- tocin administration in humans and breastfeeding outcomes. The complexity of this question is owed to both the various indications and timing of oxytocin use during the birth pro- cess and the multifactorial nature of breastfeeding and lacta- tion research outcomes. In an effort to capture all possible oxy- tocin administration during the birth process, our review in- cluded intrapartum oxytocin and/or third-stage labor admin- istration. Breastfeeding outcomes were defined as any mater- nal and infant breastfeeding-related measure.

Literature Search

Due to the exploratory nature of this investigation, the ap- proach included broad search terms and no limits on pub- lication date. We performed a Boolean search (as shown in Table 1) of PubMed Medical Subject Heading (MeSH) terms including: 1) “oxytocin,” “labor (induced),” “labor (obstet- ric),” “labor stage (third),” or “epidural analgesia”; and 2) “breastfeeding,” “feeding behavior,” “lactation,” or “lactation

(disorder),” yielding 1847 results after limiting to human studies. A duplicate search in the Cumulative Index to Nurs- ing and Allied Health Literature (CINAHL) yielded 268 cita- tions (“infant behavior” substituted for “feeding behavior”). A total of 2115 abstracts (including duplicates) were scanned for inclusion by 1) data-based studies published in English and 2) noting oxytocin administration and a breastfeeding outcome (maternal or infant). If a potential match did not mention oxytocin administration in the abstract, the full text was reviewed in detail. Induction of labor studies not evaluat- ing oxytocin specifically were excluded, as well as studies as- sessing infant bottle feeding. The resulting group consisted of 26 studies published between 1978 and 2015.

Data Evaluation

Significant heterogeneity in the study objectives, design, and outcomes complicated the evaluation of this body of litera- ture. Themajority of the studies were descriptive or secondary analysis reports (either prospective or retrospective); how- ever, one randomized controlled trial, 2 quasi-experimental studies, and 2 case-control studies also made up the sample.

While studies in this review considered oxytocin exposure during birth with at least one breastfeedingmeasure, most did not set out to study this relationship. Many noted the associ- ation between oxytocin and breastfeeding as a subanalysis of the primary aim or as a covariate or control for another objec- tive. We identified 3 groups of research objectives within the sample studies. Only 9 studies examined the effect of oxytocin use on breastfeeding. Four studies examined factors (general health and obstetric) associated with delayed lactogenesis and poor breastfeeding generally. In these reports, use of oxytocin was among many variables considered. The largest group of studies, however, sought to understand broad outcomes of specific obstetric interventions: epidural analgesia (n = 4), medication use (n = 3), active management of third-stage la- bor (AMTSL) (n = 1), or as part of an induction of labor (n = 5). These studies included a breastfeeding measure among other outcomes.

Time point of oxytocin administration varied among the studies, illustrated in Figure 1. The majority considered intra- partum oxytocin administration only. Four of these assessed the postpartum dose of oxytocin as well.25–28 Another 3 stud- ies mention that oxytocin was routinely given postpartum but was not included in the analysis in terms of exposure.29–31

Three other studies addressed the third-stage issue generally by reporting “increased need for postpartum uterotonics”

398 Volume 62, No. 4, July/August 2017

Table 1. Search Strategy for Oxytocin Use During Birth and Breastfeeding

Database Search Terms (MeSH and Keyword) Results

Unique Studies

Included

PubMed Oxytocin, labor (induced), labor (obstetric), labor stage (third),

epidural analgesia AND breastfeeding, feeding behavior, lactation,

lactation disorder

598 14

Lactogenesis (keyword) 131 3

Labor (induced) AND oxytocin 1118 4

CINAHL Oxytocin, labor (induced), obstetric care, labor stage (third), epidural

analgesia AND breastfeeding, infant behavior, lactation, lactation

disorder

89

Lactogenesis 54 1

Labor (induced) AND oxytocin 125 0

Cochrane Induced labor AND breastfeeding 13 0

Active management (third stage) labor 1 1

Scopus 1

Hand check of reference

lists

1

Total 26

Abbreviation: CINAHL, Cumulative Index to Nursing and Allied Health Literature.

Figure 1. Number of Studies by Time Point of Oxytocin Exposure

and Type of BreastfeedingMeasures Reported

MaternalMeasures of Breastfeeding (Initiation orDuration

of Breastfeeding, Physiology of Lactation).

Infant Measures of Breastfeeding (Infant Feeding

Behavior).

Both Maternal and Infant Measures.

Abbreviations: AOL, augmentation of labor; IOL, induction of labor; PP, postpartum prophylaxis.

(ie, oxytocin and other medications),32–34 or commenting on the relationship of postpartum hemorrhage and breastfeeding outcomes.35

Breastfeeding outcomes included maternal behaviors like initiation, duration of breastfeeding, measures of physio- logic milk production (eg, hormones, lactogenesis), and in- fant breastfeeding behavior. A total of 34 measures in the 26 studies were examined in relationship to oxytocin use as il- lustrated in Figure 2. Some studies reported more than one outcome in the findings. Due to the variety of study objec- tives, methods, and outcomes used in the sample, rigor of the studies was not evaluated by a standardized rubric or score. Instead, we addressed quality of the studies by assess- ing and synthesizing themes that may introduce bias or limit generalizability.

RESULTS

Breastfeeding Outcomes

No primary study outcome associated oxytocin use with a more favorable breastfeeding outcome. Data were arranged into 3 categories: 1) use of oxytocin (intrapartum and/or post- partum) and a less optimal breastfeeding outcome, 2) no association, or 3) having mixed findings. Results were la- beled mixed if they were the subanalyses of the primary aim of the study or significance was seen in certain subgroups of the sample (ie, primiparas). Of the 34 measures reported in the studies, 50% found oxytocin use was associated with a less optimal breastfeeding outcome (n = 17). Mixed or qual- ified support of less optimal outcomes was reported by 26% (n = 9), and 23% showed no differences in breastfeeding out- comes with oxytocin use or not (n = 8). Table 2 lists the mea- sures, statistical data, and information about the study design and limitations.

Initiation of Breastfeeding

Eleven studies examined associations between breastfeeding initiation and oxytocin administration; 7 studies reported on initiation only.28,32,33,36–39 Initiation of breastfeeding was de- fined by various time points ranging from 10 minutes after birth through 7 days postpartum. An additional 4 studies re- ported duration measures as well as initiation measures of breastfeeding.30,40–42

Four of these 11 studies were generated from large data sets and controlled for multiple covariates in their analyses.28,32,33,36 Two noted delay in initiation of breastfeed- ing following induction of labor and elective induction of la- bor in Latin American countries.32,33 Another reported lower breastfeeding rates at hospital discharge following AMTSL in

Journal of Midwifery &Women’s Health � www.jmwh.org 399

Figure 2. Number ofMeasures by Direction of Findings Reporting Relationship Between Oxytocin Use and BreastfeedingOutcomes

Measures Showing Less Optimal Breastfeeding Outcome With Oxytocin Use.

Measures Reporting Mixed Findings: Less Optimal Outcome With Oxytocin Use in Subgroup Analysis.

Measures Reporting No Association Between Oxytocin and Breastfeeding.

theUnited Kingdom.28 In this study, after controlling formul- tiple intrapartum factors and examining a subgroup ofwomen with low-risk, physiologic labors, AMTSL was still associated with an approximate 7% reduction in breastfeeding at 2 days postpartum.

However, the study by Prendiville,39 the only random- ized controlled trial in the sample, did not find an as- sociation between AMTSL and breastfeeding at hospital discharge. This study is limited by a lack of fidelity to the ran- domization; only 403 of 849 participants allocated to physio- logic management had it performed. In addition, the physio- logic group was also more likely to put the newborn to breast 10 minutes after birth per midwives’ recommendation.

Brown and Jordan42 also did not find thatAMTSL affected rates of breastfeeding initiation in a self-report study of breast- feeding and administration of postpartum oxytocin.42 How- ever, they did report a reduction in duration of breastfeeding at both 2 and 6 weeks postpartum among participants who had AMTSL. The most often reported reasons for cessation were pain, difficulty, and embarrassment compared towomen who had physiologic management. This study did not control for prenatal intentions to breastfeed.

Altogether, the definition of initiation of breastfeeding was variable but appeared to reflect the first several postpar- tum days. Five papers associated delayed initiation of breast- feeding with induction or augmentation of labor compared to spontaneous labor or no augmentation (postpartum use not reported)30,32,33,37 or postpartum administration of oxytocin compared to expectant management.28 Mixed findings were reported in 3 studies.36,40,41

Duration of Breastfeeding

Eight studies examined duration of breastfeeding. This was defined as the time of breastfeeding cessation,25 report of ex- clusive breastfeeding at 3 months after birth,30,31 at 6 weeks postpartum,42,43 or breastfeeding at 8 weeks.26,40,41 Shorter duration or exclusivity of breastfeeding was associated with intrapartum oxytocin use by 4 studies compared to sponta- neous labor25,26,30,31 and with postpartum use in the study by Brown and Jordan.42 Two reports hadmixed findings ondura- tion of breastfeeding.40,43 One paper reported no difference.41

The total dosage of oxytocinwas examined in terms of du- ration of breastfeeding by 2 authors. Both Gu et al26 andOlza- Fernandez31 noted that higher levels of exposure to oxytocin during the birth process were associated with reduced exclu- sive breastfeeding at 2 and 3months postpartum, respectively. Additionally, the participants in the study by Dozier et al25

most likely to cease breastfeeding by one month postpartum were those with both epidural analgesia and oxytocin expo- sure during labor (HR, 1.34; 95% confidence interval [CI], 1.00-1.79).25 Women with epidural analgesia in this study were more likely to have oxytocin administered during labor (58.8% vs 38.3%, P � .01). Breastfeeding was not analyzed by total dosage specifically in this study, but this may imply that women with epidural analgesia had more need for oxytocin administration, possibly representing higher total dosage.

Physiology of Lactation

Eight studies examined breastfeeding as a measure of phys- iologic milk production. Six of these examined lactogenesis

400 Volume 62, No. 4, July/August 2017

Table 2. Studies Reporting an Association Between Synthetic Oxytocin Use and a BreastfeedingOutcome

Author, Year, Location Design Measures Results Limitations

Gu et al,26

2015

Canada

Oxytocin Time Point

Intrapartum and postpartum

Design

Prospective longitudinal

Baby-Friendly settinga

Mixed parity sample

Self-report: Exclusivity of

breastfeeding at 2 months

Plasma oxytocin levels at 2

months

N = 386

92% of women received oxytocin

Duration

Exclusively breastfeeding mothers at 2 months

postpartum had received significantly less oxytocin

during labor (33 units) when compared to formula

(44 units) or mixed feeding mothers (43 units)

(after controlling for education level) (P � .0001)

Physiology of Lactation

Circulating oxytocin at 2 months postpartum was

positively correlated to dosage given during birth

(Pearson, 0.16, P � .01)

Did not specify the rates of analgesia,

mode of birth, indication for

oxytocin use, or neonatal problems

Breastfeeding intention not reported

Did not control for parity or other

neonatal or obstetric issues in

breastfeeding outcomes

Brimdyr et al,49

2015

United States

Oxytocin Time Point

Intrapartum

Design

Prospective Comparative

Baby-Friendly setting

Mixed parity sample

Widström’s 9 instinctive

stages of neonatal

behavior

N = 63

84% of women having oxytocin with or without

epidural analgesia

Infant Behavior