Maternal plasma levels of oxytocin during breastfeeding—A systematic review

Abstract

Introduction

The European Cooperation in Science and Technology (EU COST), supports scientific collaboration within the European Union. This article was created within the framework of the COST Action IS1405 BIRTH: "Building Intrapartum Research Through Health—An interdisciplinary whole system approach to understanding and contextualising physiological labour and birth" (http://www.cost.eu/COST_Actions/isch/IS1405). A literature review article regarding plasma levels of oxytocin in connection with labour and birth, performed within this COST action has already been published [1].

Breastfeeding is recognized as the best way to feed infants and the World Health Organization (WHO) recommends exclusive breastfeeding for the first six months of life [2, 3]. Breastfeeding gives rise to many positive effects in babies and their mothers. It for example protects against infections in new-borns and early in life and it may also reduce the occurrence of some allergic conditions, obesity, and type 1 diabetes later on in childhood. In addition, it has also been suggested to increase the level of intelligence [4]. For mothers, breastfeeding stimulates physiological and psychological changes in order to facilitate milk production and adaptations to motherhood. In addition, it gives long-term protection against diseases such as breast cancer, ovarian cancer, cardiovascular disease and diabetes type 2 [4, 5].

Breastfeeding also supports the interaction and bonding between mother and infant. Longer duration of breastfeeding was associated with more maternal sensitive responsiveness and more attachment security and less attachment disorganization in the child [6].

Oxytocin, a peptide molecule produced in the supraoptic and paraventricular nuclei (SON and PVN) of the hypothalamus, plays a key role during breastfeeding. Oxytocin released into the circulation during breastfeeding promotes milk ejection by contracting the myoepithelial cells surrounding the mammary gland alveoli and by relaxing the milk duct sphincters.

Suckling also induces a release of oxytocin from nerves within the brain where oxytocin facilitates both physiological and psychological adaptations for breastfeeding and motherhood. Oxytocin promotes prolactin release and thereby milk production. It also induces powerful anti-stress effects, including decreased blood pressure and cortisol levels, and stimulates digestive and metabolic processes [7].

The release of oxytocin into the circulation and the brain occurs in parallel in response to each breastfeeding episode. A recent publication provides an elaborate description of the mechanisms by which the release of oxytocin into the circulation and brain are coordinated [1].

It has been suggested that medical interventions during labour and birth, including caesarean section [8], epidural analgesia [9], and infusion of synthetic oxytocin [10] might negatively impact the initiation and/or continuation of breastfeeding. Medical interventions may hypothetically cause such effects by influencing the release of and effects caused by oxytocin during labour and birth in the long term.

The aim of this study was to review plasma levels of oxytocin levels in response to breastfeeding. Also, other oxytocin linked effects presented in the identified articles as well as data regarding effects of medical interventions during labour and birth are reported. Data obtained within the same article allows more detailed investigations of the relationship between oxytocin and oxytocin linked effects, than does data presented in separate articles. The same applies for articles on the effects of medical interventions.

Methods

A systematic literature search, with the aim to summarize the knowledge regarding oxytocin levels in response to breastfeeding, was carried out according to the PRISMA statement [11] and using Covidence©, an online platform for systematic reviews [12]. The main inclusion criterion was plasma levels of oxytocin in response to breastfeeding, All the inclusion criteria are shown in Table 1.

The search strings were created by KUM, AEB and SB together with librarians from the University of Queensland and searches were performed in the following databases: Pubmed, Scopus, CINAHL, and PsycINFO in September 2017. An additional literature search based on the same search string was performed in September 2019.

Procedure for selection of studies

In 2017, 453 articles were identified via database searches (PubMed n = 305, Scopus n = 91, CINAHL n = 7, and PsycINFO n = 50). Fifteen additional articles were identified through other sources. Forty duplicates were removed from the 468 articles leaving 428 articles. By screening of titles and abstracts, 268 of the 468 articles were excluded. After full-text screening of the remaining 160 articles, 28 articles were identified that met the inclusion criteria, were included in this review. A last search was performed in September 2019. Additional 34 papers were identified. After removing duplicates and screening of titles and abstracts, two full text papers were included and reviewed. One paper was excluded due to no reporting of oxytocin levels [13] and one paper met the inclusion/exclusion criteria [14].

All together 29 articles were identified in which maternal oxytocin levels were recorded during breastfeeding or other types of breast stimulation [14–42]. Note that the 29 included articles are based on 25 clinical studies, as data from 3 of the clinical studies had been split and published in 2 separate articles, thus [20, 34] and [30, 32] and [36, 37] were based on the same clinical studies. For 2 of the other included articles, Jonas et. al. 2009 [24] and Uvnäs Moberg et. al. 1990 [37] additional material regarding breastfeeding induced effects had been published as separate articles [43–45] and [46, 47] respectively. Data from these additional studies have also been included in the tables. Altogether 601 women participated in the studies summarized.

At each stage, articles were screened by at least two authors working independently in pairs (AEB, KUM, CM, KL, SB & ZP) based on the inclusion and exclusion criteria (Table 1). In case inclusion was unclear, an expert third author (KUM) was involved. Final decisions were agreed by SB & KUM. The selection process is illustrated in a flow diagram (Fig 1).

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Fig 1

Flow diagram of study selection.

Results

Discussion

Articles in which blood/plasma levels of oxytocin levels in response to breastfeeding had been recorded were included in this systematic literature review. In some of the selected articles (and in some of the associated articles based on the same clinical studies) information was also reported regarding prolactin, stress, nutrition, metabolism, as well as personality and mood. Some studies also reported on effects of medical interventions in connection with birth. Since the primary objective of this systematic literature review was to summarize studies that measured breastfeeding-related oxytocin levels, we obviously did not identify all studies regarding the secondary variables mentioned above. We chose to include the secondary oxytocin linked effects because data obtained within the same article may reveal more causal with oxytocin relationships than data obtained from different articles. In a sense this gives a deeper meaning to the oxytocin levels recorded because they also become a proxy for the secondary oxytocin linked endocrine, physiological and psychological effects.

The studies included in this review differ in many ways. Some studies were performed during early breastfeeding and some later on during established breastfeeding. In some studies oxytocin release in response to suckling was studied immediately after birth. The timing of blood samples was also very different. The number of blood samples collected in the different studies varied between 2 and 24 and the frequency by which samples were collected between 30 seconds and 20 minutes. In other studies, as much as 24 blood samples were collected, some of them with 30 second intervals. We have tried to describe and summarize the results regarding breastfeeding induced effects on oxytocin level despite these methodological differences.

All of the studies showed that suckling is associated with oxytocin release [14–42]. In early breastfeeding, the release of oxytocin occurred in pulses, which later on during breastfeeding coalesced into a large sustained peak [23, 24, 28, 30, 32, 35, 37, 40]. There were correlations between oxytocin levels and milk yield in several of the included studies and also correlations with duration of breastfeeding and weight of the newborn [14, 22, 25, 26, 28–30, 32, 35–37, 52]. The correlation between milk yield and the number of oxytocin pulses is of particular interest as each peak of oxytocin is linked to milk ejection [53]. Taken together, these data suggest that oxytocin levels in response to breast feeding correlates with milk production and also for the duration of breastfeeding.

From this perspective, it is of interest that the number of oxytocin peaks released during breastfeeding was reduced by relatively minor stressors, such as noise and mental activity (concentration), indicating that both an “external” and “internal” environment characterized by calmness are of importance for the breastfeeding mother in order promote the milk-ejection reflex and thereby milk production [35]. Also maternal mood influenced oxytocin levels, as depression was associated with lower oxytocin release in response to breastfeeding [34].

Oxytocin produced in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus is released from the posterior pituitary into the circulation in response to breastfeeding in order to stimulate milk ejection. However, oxytocin is at the same time released from oxytocinergic nerves that project from the PVN in the hypothalamus to many regulatory areas in the brain. In this way breastfeeding may be accompanied by many different physiological and psychological adaptations, which help mothers to cope with the demands of breastfeeding and motherhood. For a more elaborate description of the central effects of oxytocin and how oxytocin release into the circulation and the brain are coordinated, see Uvnäs Moberg et. al. 2019 [1].

The present results identified multiple adaptive effects of breastfeeding, which are linked to activation of the oxytocin system. These effects include facilitation of prolactin release, decreased activity in the stress system (HPA axis: ACTH and cortisol and the sympathetic nervous system: blood pressure and heart rate) and increased function of the parasympathetic part of the autonomic nervous system, including activation of the gastrointestinal tract by the vagal nerve. Oxytocin release was also correlated with mental adaptations that facilitate motherhood such as increased levels of social interaction and decreased anxiety [1]. The oxytocinergic pathways in the brain that may be involved in these actions are illustrated in Fig 2.

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Fig 2

Schematic illustration of the oxytocin pathways activated during breastfeeding.

As reported in this review prolactin was released by suckling [15, 20, 21, 23–25, 28–30, 32, 35, 37, 38, 40, 41]. The release of prolactin, however, differed from oxytocin release caused by suckling in many ways. During a breastfeeding episode, oxytocin is released within minutes and in a pulsatile pattern, whereas prolactin levels increase more slowly, are not pulsatile and more long lasting than oxytocin levels. Nor could prolactin be released by breast-massage and prolactin release was less sensitive to acute stressors than oxytocin release. Altogether, these data indicate that oxytocin and prolactin release are in part mediated by separate mechanisms and that prolactin release is more resilient to stress than is oxytocin [35]. Nevertheless, oxytocin exerts an over-riding facilitating influence on prolactin release, via the oxytocin-containing nerves that extend from the PVN to the prolactin-producing cells in the anterior pituitary, as shown above and in Fig 2. In this way, oxytocin stimulates milk production as well as milk ejection [7].

Breastfeeding was also linked to anti-stress effects, with decreases in ACTH, cortisol and blood pressure during a breastfeeding episode [16–18, 20, 30, 32, 34, 42–44, 51]. The decrease in ACTH levels was linked to the duration of suckling reflecting the inhibitory effect of oxytocin released within the PVN on Corticotropin-releasing factor (CRF), which regulates ACTH release. In addition, oxytocin may have a direct inhibitory effect on ACTH via nerves linking the PVN to ACTH-producing cells in the anterior pituitary (Fig 2).

In these studies, the decrease in cortisol levels was not only associated with reduced ACTH levels, but also to the duration of skin-to-skin contact. This latter effect most likely reflects the influence of oxytocin nerves that project to areas in the brain that regulate the function of the autonomic nervous system, and which are activated in response to stimulation of sensory nerves that originate in the skin. In the same way the decrease in blood pressure induced by suckling involves an oxytocin mediated decrease of the activity in the sympathetic nervous system [7, 49].

Lowering of ACTH and cortisol levels was also induced in response to suckling in non-breastfeeding women, suggesting that suckling may induce stress reduction in the absence of breastfeeding [18].

One of the studies showed that the sensitivity to stress is decreased for some hours following breastfeeding, indicating that breastfeeding is, in addition to the acute anti stress effect, linked to a more long-term stress-buffering effect [20]. Similar findings have been reported in other studies [54]. Taken together these data show that mothers are subject to powerful anti-stress effects during suckling, which may help them relax and adapt to breastfeeding. The antioxidant effects observed in response to skin-to-skin contact represent yet another “health” promoting effect of breastfeeding [44].

The data in this review also showed that thirst is increased and that, absorption, digestion and metabolism of nutrients were optimized by breastfeeding-related oxytocin release [22, 46, 47]. These effects assist in adapting the mother to the high demands of nutrition and fluid intake during breastfeeding. Oxytocin influences the gastrointestinal function by increasing the function of the vagal nerve. For example, it may decrease the release somatostatin, a hormone produced in the gastrointestinal tract, which exerts inhibitory effects on gastrointestinal function [7]. Oxytocin (and breastfeeding) lower the levels of somatostatin and thereby the function of the gastrointestinal tract increases. The finding of an inverse relationship between levels of oxytocin and somatostatin (which inhibits the activity of the endocrine system of the gastrointestinal tract) also supports the important role oxytocin has in adapting maternal metabolism to the demands of breastfeeding [55].

In several of the included studies, the personality inventory, Karolinska Scales of Personality (KSP) was applied to breastfeeding women [30, 36, 39, 51]. The KSP has 135 items in a four-point response format. It consists of 15 self-reported scales that can be divided into the anxiety proneness scales, the extroversion related scales, the socialization scale, the social desirability scale and the aggression-hostility related scales. The KSP is standardized for sex and age and the normative sample is based on 200 non-pregnant or lactating randomly selected women. The test has a high validity and retest stability [56, 57].

It seems that oxytocin release during breastfeeding influences maternal psychology in a way that facilitates motherhood, i.e. levels of anxiety and aggression are decreased, and social functioning increased. Breastfeeding is also linked to increased sensitivity in the mother and other mental adaptations that facilitate motherhood [6]. In a study performed by Strathearn et. al., 2009, dopamine activity in the maternal brain was increased in response to their own smiling baby’s photo. This increase in dopamine activity was related to maternal oxytocin levels and also to secure attachment [58].

These changes, which are linked to oxytocin levels are beneficial for the mother and might constitute a slight reflection of the more developed maternal behaviours that occur in other mammals in response to central oxytocin release, during parturition and suckling [59]. Altogether, these data indicate that the oxytocin release associated with breastfeeding contributes to the development of positive maternal experiences, psychological skills and physiological adaptations.

Mechanical breast stimulation was associated with oxytocin release and milk yield of similar magnitude as breastfeeding. Mechanical breast stimulation also stimulated prolactin release and decreased ACTH and cortisol levels [17, 25, 41]. These data suggest that mechanical breast stimulation is associated with at least some of the oxytocin-induced adaptations seen in response to breastfeeding [7].

By contrast, none of these adaptations were induced when mothers were bottle-feeding their babies [23]. Also, other studies have demonstrated that bottle feeding mothers are less sensitive in the communication with their babies and that they have higher stress levels than breastfeeding mothers [60].

Medical interventions during labour and birth have been associated with disturbed breastfeeding [8–10]. Such effects might potentially be mediated by a disrupted function of the oxytocin system during labour and birth, which then persists during breastfeeding. During labour the release of oxytocin is triggered by pressure from the baby’s head on the cervix and the vagina in response to uterine contractions (the Ferguson reflex). Less oxytocin may be released during caesarean sections (especially by prelabour caesarean sections due to the absence of uterine contractions and labour) than during vaginal birth [1]. Also, epidural analgesia may reduce oxytocin release in connection with birth. Epidural analgesia blocks the transmission in pain fibres, but also the transmission in the nerve fibres mediating the Ferguson reflex and thereby oxytocin release [61]. It is biologically plausible that such effects on oxytocin release induced by medical interventions in connection with birth could become long-lasting, with consequences for breastfeeding outcomes and other oxytocin-linked effects [1, 62]. In fact, results from some of the included studies indicate that oxytocin release in response to breastfeeding may be deranged by medical interventions. In women who had an emergency cesarean section, oxytocin release in response to early breastfeeding was significantly reduced [30, 32]. Prolactin release and maternal adaptations were also reduced, possibly as a consequence of the reduced release of oxytocin in the brain during breastfeeding [30, 32]. In another study mothers who had had a prelabour caesarean section, skin-to-skin contact immediately after birth did not stimulate maternal oxytocin release or maternal adaptations as measured with the KSP 2 days later [39]. Epidural analgesia was linked to decreased prolactin levels and decreased maternal adaptations [24, 51]. Taken together these data suggest that mothers who have given birth by caesarean or have had an epidural analgesia might at least initially during breastfeeding have a compromised function of the oxytocin system. This may contribute to the breastfeeding difficulties that women can experience following caesarean section and epidural analgesia [8, 9].

Both prolactin release, and maternal mental adaptations were, however, more strongly developed in women who received synthetic oxytocin infusions during labour, in comparison to those who did not receive any medical interventions. Some of these effects were dose-dependent [24, 51]. In addition, infusions of synthetic oxytocin seemed to counteract the negative influence of epidural analgesia on maternal mental adaptations [51]. Infusions of synthetic oxytocin also restored the release of endogenous oxytocin in response to early skin-to-skin contact, as well as the development of maternal mental adaptations, which was otherwise not developed following prelabour caesarean section [39]. These central effects of synthetic oxytocin are probably induced indirectly via nervous reflexes, such as reinforcement of the Ferguson reflex (1).

In addition, the repetitive release of endogenous oxytocin during breastfeeding may counteract some of the negative effects of caesarean section and epidural analgesia on prolactin release and maternal mental adaptations [51]. In this way breastfeeding may counteract some of the negative consequences caused by medical interventions that are linked to reduction of oxytocin release in labour and birth.

The repetitive release of oxytocin occurring during breastfeeding may also explain why basal blood pressure was significantly decreased after 6 weeks of breastfeeding [45]. Such long term effects of repeated oxytocin exposure may also explain why breastfeeding is linked to long term health-promoting effects [63]. In particular, there are long term benefits for different types of cardiovascular disease, including hypertension, stroke, heart infarction and diabetes type 2, with greater effects for longer duration of lactation [4, 5, 64–66].

Also the infants profit from breastfeeding beyond being exposed to the beneficial components of breastmilk [67]. Skin-to-skin contact and suckling promote oxytocin release also in the baby [7], with possible long term beneficial effects on bonding, health and wellbeing [4, 6, 7].

Taken together this review shows that breastfeeding is more than a transfer of breastmilk from mother to infant. By stimulating the release of oxytocin into the circulation and into the brain, it not only stimulates milk ejection, it also stimulates neuroendocrine processes that facilitate milk production and maternal physiological and psychological adaptations. Also, the baby is exposed to oxytocin during breastfeeding with possible long-term beneficial effects on health and wellbeing. When considering these positive aspects of breastfeeding it is obvious that breastfeeding should be valued beyond its role as a source of breastmilk for the baby.

Conclusions and implications for clinical practice

The Baby-Friendly Hospital Initiative (BFHI) which is supported by the WHO focuses on breastfeeding for healthy, mother-infant dyads. To stimulate and facilitate breastfeeding “The ten steps to successful breastfeeding” have been formulated. They recommend immediate and uninterrupted skin-to-skin contact and support of mothers to initiate breastfeeding as soon as possible after birth. They also support mothers to initiate and maintain breastfeeding and how to manage common breastfeeding difficulties. Further, they support the mothers and their infants to remain together and to practise rooming in the maternity ward and not to provide breastfed newborns any food or fluids other than breast milk, unless medically indicated. Finally, they also provide support for mothers to recognize and respond to their infants’ cues for feeding. There is substantial evidence that implementing the “Ten Steps” significantly improves breastfeeding rates. A systematic review of 58 studies on maternity and newborn care published in 2016 demonstrated clearly that adherence to the Ten Steps impacts early initiation of breastfeeding immediately after birth, exclusive breastfeeding, and total duration of breastfeeding [68].

In fact, all the practical recommendations described within “The ten steps” are consistent with an optimized stimulation of oxytocin release. As summarized in this review oxytocin is released in response to skin-to-skin contact and breastfeeding to cause milk ejection and to promote milk production. It also induces physiological changes and psychological adaptations to facilitate motherhood. The relevance of the “Ten steps” recommendations is therefore supported by their link to activation of the oxytocin system. More research should be performed to increase the knowledge about the link between the practical recommendations mention above in BFHI and the activation of the oxytocin system in mothers and their babies.

Repeated exposure to oxytocin with each episode of breastfeeding, may contribute to the lifelong benefits of breastfeeding for mother and baby and it may even counteract some negative consequences of medical interventions.

It is of importance that health professionals receive information about how oxytocin and oxytocin linked effects promote breastfeeding and how this system is reinforced by the recommendations of BFHI.

Supporting information

Funding Statement

This article is based upon work funded by the COST Action IS1405 BIRTH: "Building Intrapartum Research Through Health - An interdisciplinary whole system approach to understanding and contextualizing physiological labour and birth" (http://www.cost.eu/COST_Actions/isch/IS1405), supported by EU COST (European Cooperation in Science and Technology).

Data Availability

All relevant data are within the paper.

References