Touch medicine: bridging the gap between recent insights from touch research and clinical medicine and its special significance for the treatment of affective disorders.

Interpersonal touch represents the primal sensory experience between humans, fostering social bonding from the cradle to the death bed. In recent decades "affective touch" has been intensely studied, stimulated by the discovery of a population of mechanosensitive unmyelinated C-tactile afferents in mammalian skin. A lack of touch in childhood is associated with negative consequences for psychosocial and physical health and the benefits of professional touch techniques in the prevention and treatment of various diseases have been shown over and over again in clinical studies. However, its application in mainstream clinical applications remains limited. To bridge the gap between recent discoveries in touch research and clinical medicine, we propose the establishment of a new discipline: 'Touch Medicine'. Here, we unfold the potential of Touch Medicine by focusing on the treatment of depression, which in our view is primarily a disorder of the lived body. Controlled studies and systematic reviews have demonstrated the antidepressant, anxiolytic and analgesic effects of specific massage techniques. Underlying mechanisms of action are currently under investigation, ranging from interoceptive, endocrinological, to stress-related or psychological underpinnings. Touch Medicine represents a novel interdisciplinary field connected to various medical specialities such as neonatology, pediatrics, pain medicine, neurology, psychiatry, and geriatrics - but also clinical psychology and psychosomatic medicine might benefit from the integration of these findings into their daily practice.

The Yin and Yang of the oxytocin and stress systems: opposites, yet interdependent and intertwined determinants of lifelong health trajectories.

During parturition and the immediate post-partum period there are two opposite, yet interdependent and intertwined systems that are highly active and play a role in determining lifelong health and behaviour in both the mother and her infant: the stress and the anti-stress (oxytocin) system. Before attempting to understand how the environment around birth determines long-term health trajectories, it is essential to understand how these two systems operate and how they interact. Here, we discuss together the hormonal and neuronal arms of both the hypothalamic-pituitary-adrenal (HPA) axis and the oxytocinergic systems and how they interact. Although the HPA axis and glucocorticoid stress axis are well studied, the role of oxytocin as an extremely powerful anti-stress hormone deserves more attention. It is clear that these anti-stress effects depend on oxytocinergic nerves emanating from the supraoptic nucleus (SON) and paraventricular nucleus (PVN), and project to multiple sites at which the stress system is regulated. These, include projections to corticotropin releasing hormone (CRH) neurons within the PVN, to the anterior pituitary, to areas involved in sympathetic and parasympathetic nervous control, to NA neurons in the locus coeruleus (LC), and to CRH neurons in the amygdala. In the context of the interaction between the HPA axis and the oxytocin system birth is a particularly interesting period as, for both the mother and the infant, both systems are very strongly activated within the same narrow time window. Data suggest that the HPA axis and the oxytocin system appear to interact in this early-life period, with effects lasting many years. If mother-child skin-to-skin contact occurs almost immediately postpartum, the effects of the anti-stress (oxytocin) system become more prominent, moderating lifelong health trajectories. There is clear evidence that HPA axis activity during this time is dependent on the balance between the HPA axis and the oxytocin system, the latter being reinforced by specific somatosensory inputs, and this has long-term consequences for stress reactivity.

The physiology and pharmacology of oxytocin in labor and in the peripartum period.

Oxytocin is a reproductive hormone implicated in the process of parturition and widely used during labor. Oxytocin is produced within the supraoptic nucleus and paraventricular nucleus of the hypothalamus and released from the posterior pituitary lobe into the circulation. Oxytocin is released in pulses with increasing frequency and amplitude in the first and second stages of labor, with a few pulses released in the third stage of labor. During labor, the fetus exerts pressure on the cervix of the uterus, which activates a feedforward reflex-the Ferguson reflex-which releases oxytocin. When myometrial contractions activate sympathetic nerves, it decreases oxytocin release. When oxytocin binds to specific myometrial oxytocin receptors, it induces myometrial contractions. High levels of circulating estrogen at term make the receptors more sensitive. In addition, oxytocin stimulates prostaglandin synthesis and release in the decidua and chorioamniotic membranes by activating a specific type of oxytocin receptor. Prostaglandins contribute to cervical ripening and uterine contractility in labor. The oxytocin system in the brain has been implicated in decreasing maternal levels of fear, pain, and stress, and oxytocin release and function during labor are stimulated by a social support. Moreover, studies suggest, but have not yet proven, that labor may be associated with long-term, behavioral and physiological adaptations in the mother and infant, possibly involving epigenetic modulation of oxytocin production and release and the oxytocin receptor. In addition, infusions of synthetic oxytocin are used to induce and augment labor. Oxytocin may be administered according to different dose regimens at increasing rates from 1 to 3 mIU/min to a maximal rate of 36 mIU/min at 15- to 40-minute intervals. The total amount of synthetic oxytocin given during labor can be 5 to 10 IU, but lower and higher amounts of oxytocin may also be given. High-dose infusions of oxytocin may shorten the duration of labor by up to 2 hours compared with no infusion of oxytocin; however, it does not lower the frequency of cesarean delivery. When synthetic oxytocin is administered, the plasma concentration of oxytocin increases in a dose-dependent way: at infusion rates of 20 to 30 mIU/min, plasma oxytocin concentration increases approximately 2- to 3-fold above the basal level. Synthetic oxytocin administered at recommended dose levels is not likely to cross the placenta or maternal blood-brain barrier. Synthetic oxytocin should be administered with caution as high levels may induce tachystole and uterine overstimulation, with potentially negative consequences for the fetus and possibly the mother. Of note, 5 to 10 IU of synthetic oxytocin is often routinely given as an intravenous or intramuscular bolus administration after delivery to induce uterine contractility, which, in turn, induces uterine separation of the placenta and prevents postpartum hemorrhage. Furthermore, it promotes the expulsion of the placenta.

Oxytocin levels and self-reported anxiety during interactions between humans and cows.

Introduction: Positive social interactions with farm animals may have therapeutic benefits on humans by increasing brain oxytocin secretion, as inferred from circulating oxytocin levels. The aim of this observational study was to investigate acute changes in human plasma oxytocin levels and state anxiety associated with interactions with dairy cows. Methods: Data were collected from 18 healthy female nursing students who performed stroking and brushing of an unfamiliar cow for 15 min. Blood samples were drawn before entering the cowshed (T1, baseline), and after 5 (T2) and 15 (T3) min of interaction with a cow. At T1 and T3, the students filled out the Norwegian version of the Spielberger State-Trait Anxiety Inventory-State Subscale (STAI-SS). Results: Across participants, no significant changes in average plasma oxytocin concentration were detected between time points (p>0.05). There was, however, a modest decline in the STAI-SS scores between T1 and T3 (p=0.015) and a positive correlation between the change in individual level of state anxiety between T1 and T3 and the change in OT concentration of the same individual between T2 and T3 (p = 0.045). Discussion: The results suggest that friendly social interactions with cows are beneficial in lowering state anxiety, but any relationship with release of OT into the circulation was complex and variable across individuals. The acute reduction in state anxiety lends support to the value of interacting with farm animals in the context of Green Care for people with mental health challenges.

Maternal and newborn plasma oxytocin levels in response to maternal synthetic oxytocin administration during labour, birth and postpartum - a systematic review with implications for the function of the oxytocinergic system.

BACKGROUND: The reproductive hormone oxytocin facilitates labour, birth and postpartum adaptations for women and newborns. Synthetic oxytocin is commonly given to induce or augment labour and to decrease postpartum bleeding. AIM: To systematically review studies measuring plasma oxytocin levels in women and newborns following maternal administration of synthetic oxytocin during labour, birth and/or postpartum and to consider possible impacts on endogenous oxytocin and related systems. METHODS: Systematic searches of PubMed, CINAHL, PsycInfo and Scopus databases followed PRISMA guidelines, including all peer-reviewed studies in languages understood by the authors. Thirty-five publications met inclusion criteria, including 1373 women and 148 newborns. Studies varied substantially in design and methodology, so classical meta-analysis was not possible. Therefore, results were categorized, analysed and summarised in text and tables. RESULTS: Infusions of synthetic oxytocin increased maternal plasma oxytocin levels dose-dependently; doubling the infusion rate approximately doubled oxytocin levels. Infusions below 10 milliunits per minute (mU/min) did not raise maternal oxytocin above the range observed in physiological labour. At high intrapartum infusion rates (up to 32 mU/min) maternal plasma oxytocin reached 2-3 times physiological levels. Postpartum synthetic oxytocin regimens used comparatively higher doses with shorter duration compared to labour, giving greater but transient maternal oxytocin elevations. Total postpartum dose was comparable to total intrapartum dose following vaginal birth, but post-caesarean dosages were higher. Newborn oxytocin levels were higher in the umbilical artery vs. umbilical vein, and both were higher than maternal plasma levels, implying substantial fetal oxytocin production in labour. Newborn oxytocin levels were not further elevated following maternal intrapartum synthetic oxytocin, suggesting that synthetic oxytocin at clinical doses does not cross from mother to fetus. CONCLUSIONS: Synthetic oxytocin infusion during labour increased maternal plasma oxytocin levels 2-3-fold at the highest doses and was not associated with neonatal plasma oxytocin elevations. Therefore, direct effects from synthetic oxytocin transfer to maternal brain or fetus are unlikely. However, infusions of synthetic oxytocin in labour change uterine contraction patterns. This may influence uterine blood flow and maternal autonomic nervous system activity, potentially harming the fetus and increasing maternal pain and stress.

Impact of Birthing Room Design on Maternal Childbirth Experience: Results From the Room4Birth Randomized Trial.

OBJECTIVE: To study the effect of the birthing room design on nulliparous women's childbirth experience up to 1 year after birth. BACKGROUND: Although it is known that the birth environment can support or hinder birth processes, the impact of the birthing room design on maternal childbirth experience over time is insufficiently studied. METHODS: The Room4Birth randomized controlled trial was conducted at a labor ward in Sweden. Nulliparous women in active stage of spontaneous labor were randomized (n = 406) to either a regular birthing room (n = 202) or a new birthing room designed with more person-centered considerations (n = 204). Childbirth experiences were measured 2 hr, 3 months, and 12 months after birth by using a Visual Analogue Scale of Overall Childbirth Experience (VAS-OCE), the Fear of Birth Scale (FOBS), and the Childbirth Experience Questionnaire (CEQ2). RESULTS: Women randomized to the new room had a more positive childbirth experience reported on the VAS-OCE 3 months (p = .002) and 12 months (p = .021) after birth compared to women randomized to a regular room. Women in the new room also scored higher in the total CEQ2 score (p = .039) and within the CEQ2 subdomain own capacity after 3 months (p = .028). The remaining CEQ2 domains and the FOBS scores did not differ between the groups. CONCLUSIONS: These findings show that a birthing room offering more possibilities to change features and functions in the room according to personal needs and requirements, positively affects the childbirth experience of nulliparous women 3 and 12 months after they have given birth.

A weighted blanket increases pre-sleep salivary concentrations of melatonin in young, healthy adults.

Weighted blankets have emerged as a potential non-pharmacological intervention to ease conditions such as insomnia and anxiety. Despite a lack of experimental evidence, these alleged effects are frequently attributed to a reduced activity of the endogenous stress systems and an increased release of hormones such as oxytocin and melatonin. Thus, the aim of the present in-laboratory crossover study (26 young and healthy participants, including 15 men and 11 women) was to investigate if using a weighted blanket (~12% of body weight) at bedtime resulted in higher salivary concentrations of melatonin and oxytocin compared with a light blanket (~2.4% of body weight). We also examined possible differences in salivary concentrations of the stress hormone cortisol, salivary alpha-amylase activity (as an indicative metric of sympathetic nervous system activity), subjective sleepiness, and sleep duration. When using a weighted blanket, the 1 hour increase of salivary melatonin from baseline (i.e., 22:00) to lights off (i.e., 23:00) was about 32% higher (p = 0.011). No other significant differences were found between the blanket conditions, including subjective sleepiness and total sleep duration. Our study is the first to suggest that using a weighted blanket may result in a more significant release of melatonin at bedtime. Future studies should investigate whether the stimulatory effect on melatonin secretion is observed on a nightly basis when frequently using a weighted blanket over weeks to months. It remains to be determined whether the observed increase in melatonin may be therapeutically relevant for the previously described effects of the weighted blanket on insomnia and anxiety.

Room4Birth - The effect of giving birth in a hospital birthing room designed with person-centred considerations: A Swedish randomised controlled trial.

OBJECTIVE: To evaluate if a birthing room designed with person-centred considerations improves labour and birth outcomes for nulliparous women when compared to regular birthing rooms. METHODS: A randomised controlled trial was conducted at a Swedish labour ward between January 2019 and October 2020. Nulliparous women in spontaneous labour were randomised either to a birthing room designed with person-centred considerations (New room) or a Regular room. The primary outcome was a composite of four variables: vaginal non-instrumental birth; no oxytocin augmentation; postpartum blood loss < 1000 ml; and a positive childbirth experience. To detect a difference of 8% between the groups, 1274 study participants were needed, but the trial was terminated early due to consequences of the Covid-19 pandemic. RESULTS: A total of 406 women were randomised; 204 to the New room and 202 to the Regular room. There was no significant difference in the primary outcome between the groups (42.2% versus 35.1%; odds ratio: 1.35, 95% Confidence Interval 0.90-2.01; p = 0.18). Participants in the New room used epidural analgesia to a lower extent (54.4% versus 65.3%, relative risk: 0.83, 95% Confidence Interval 0.71-0.98; p = 0.03) and reported to a higher degree that the room contributed to a sense of safety, control, and integrity (p=<0.001). CONCLUSIONS: The hypothesis that the New room would improve the primary outcome could not be verified. Considering the early discontinuation of the study, results should be interpreted with caution. Nevertheless, analyses of our secondary outcomes emphasise the experiential value of the built birth environment in improving care for labouring women.

Feeding and Manual Brushing Influence the Release of Oxytocin, ACTH and Cortisol Differently During Milking in Dairy Cows.

Aim: This study aimed to examine the effects of feeding or abdominal brushing on the release of the hormones oxytocin, ACTH and cortisol during milking in dairy cows. Methods: Twelve cows in early lactation were used (2 × 2 factorial experimental design), testing the effects of two types of sensory stimulation during milking over a 3 day period; feeding concentrate or manual abdominal brushing (1 stroke/s). Blood samples for hormone analyses were collected at time at -15, -1, 0 (onset of cluster), every min for 8 min, at 10, 12, 14, 16, 30, and 60 min. Hormone levels were assayed and AUC was calculated. Results: Milking was associated with an immediate and significant rise of oxytocin. When milking was combined with feeding, significantly higher levels of oxytocin were observed at 2 and 4 mins (p < 0.05). No effect of brushing on oxytocin levels was observed. Milking alone was associated with a significant rise of ACTH levels. Feeding in connection with milking reduced the immediate rise of ACTH levels (p < 0.05) and AUC (p < 0.02), whereas no effects of brushing were found. Milking caused a progressive rise of cortisol levels. Concomitant feeding did not influence cortisol levels, whereas brushing significantly decreased cortisol levels at 1, 5 and 14 mins after onset of milking (p < 0.05). Conclusion: Feeding increases oxytocin release in response to milking and decreases ACTH levels. Abdominal brushing did not influence these variables, but decreased cortisol levels. These data demonstrate that activation of afferent vagal nerve fibres and of cutaneous sensory nerves originating from the abdominal skin in front of the udder influence milking related hormone release differently.

Epidural Analgesia With or Without Oxytocin, but Not Oxytocin Alone, Administered During Birth Disturbs Infant Pre-feeding and Sucking Behaviors and Maternal Oxytocin Levels in Connection With a Breastfeed Two Days Later.

Aims This work aimed to study consequences of medical interventions in connection with birth on infant pre-feeding and feeding behaviors and on maternal oxytocin levels in connection with a breastfeed 2 days later. Materials and Methods Mothers and their full-term newborns (n = 41) were videotaped during a breastfeed 2 days after birth. Duration and quality of rooting [Infant Breastfeeding Assessment Tool (IBFAT)] were assessed. Maternal blood samples were collected, oxytocin levels were analyzed, and mean oxytocin level and variance were calculated. Data on medical interventions during birth, number of breastfeedings, and infant weight loss since birth were recorded. Data were analyzed using logistic regression models. Results The duration of infant rooting was significantly shorter when the mother had received epidural analgesia. The shorter the duration of infant rooting, the more often infants had breastfed and the greater was the infant weight loss since birth. Mothers with epidural analgesia with oxytocin had the lowest oxytocin mean levels in connection with a breastfeed. Oxytocin variance correlated positively with quality of rooting and correlated negatively with infant weight loss. In the control group alone, we found similar patterns of associations with oxytocin levels. Conclusion Epidural analgesia and epidural analgesia with oxytocin infusion in connection with birth negatively influenced infant rooting behavior and maternal mean oxytocin levels, respectively. Oxytocin infusion alone was without effect. The data also suggest that infants who suck well stimulate oxytocin release more efficiently, as expressed by a high oxytocin variance, leading to a better stimulation of milk production and consequently to a reduced infant weight loss 2 days after birth.

The Oxytocinergic System as a Mediator of Anti-stress and Instorative Effects Induced by Nature: The Calm and Connection Theory.

Ever more research results demonstrate that human health and wellbeing are positively affected by stays in and/or exposure to natural areas, which leads, among other things, to a reduction in high stress levels. However, according to the studies, these natural areas must meet certain qualities. The qualities that are considered to be most health promoting are those that humans perceive in a positive way. Theories about how natural areas can reduce people's stress levels and improve their coping skills have mainly focused on how certain natural areas that are perceived as safe reduce the activity of the hypothalamic-pituitary-adrenal axis and consequent reduction of cortisol levels. This article discusses studies containing descriptions of how participants in rehabilitation perceive and react to natural phenomena. The common core variable in the analyzed studies was the experience of calm and connection, and this experience was associated with a reduction in stress levels and with being able to develop health and coping skills. We suggest that this experience provides a possible role for the oxytocinergic system to act as a physiological mediator for the positive and health-promoting effects in humans caused by nature. The theory is mainly based on analogies framed by theories and data from the fields of environmental psychology, horticulture, landscape architecture, medicine, and neuroscience. Oxytocin promotes different kinds of social interaction and bonding and exerts stress-reducing and healing effects. We propose that oxytocin is released by certain natural phenomena experienced as positive to decrease the levels of fear and stress, increase levels of trust and wellbeing, and possibly develop attachment or bonding to nature. By these effects, oxytocin will induce health-promoting effects. In situations characterized by low levels of fear and stress in response to release of oxytocin, the capacity for "growth" or psychological development might also be promoted. Such an instorative effect of nature, i.e., the capacity of nature to promote reorientation and the creation of new coping strategies, might hence represent an additional aspect of the oxytocin-linked effect profile, triggered in connection with certain nature phenomena. We conclude by proposing that the stress-relieving, health-promoting, restorative, and instorative effects of nature may involve activation of the oxytocinergic system.

Can intravenous oxytocin infusion counteract hyperinflammation in COVID-19 infected patients?

OBJECTIVES: Based on its well-documented anti-inflammatory and restorative properties we propose trials with the natural hormone oxytocin for treatment of hospitalised Covid-19 patients. METHODS: We searched for, retrieved, and commented on specific literature regarding multiple functions of oxytocin with a special focus on its modulation of inflammatory, immune, and restorative functions. RESULTS: Available data gathered in animals and humans support the anti-inflammatory properties of oxytocin. The multiple anti-inflammatory effects of oxytocin have been demonstrated in vitro and in vivo in various animal models and also in humans in response to intravenous infusion of oxytocin. Furthermore, oxytocin has been documented to activate several types of protective and restorative mechanisms and to exert positive effects on the immune system. CONCLUSIONS: In addition, to being anti-inflammatory, it may be hypothesised, that oxytocin may be less suppressive on adaptive immune systems, as compared with glucocorticoids. Finally, by its restorative effects coupled with its anti-stress and healing properties, oxytocin may shorten the recovery period of the Covid-19 patients.

Are There Epigenetic Oxytocin-Mediated Effects on the Mother and Infant during Physiological Childbirth?

INTRODUCTION: Studies have shown that long-term positive behavioural and physiological changes are induced in connection with vaginal, physiological birth, and skin-to-skin contact after birth in mothers and babies. Some of these effects are consistent with the effect profile of oxytocin. This scoping review explores whether epigenetic changes of the oxytocin gene and of the oxytocin receptor gene (OTR) are involved in these effects. METHODS: We searched Pubmed, Medline, BioMed Central, Cochrane Library, OVID, and Web of Science for evidence of epigenetic changes in connection with childbirth in humans, with a particular focus on the oxytocin system. RESULTS: There were no published studies identified that were related to epigenetic changes of oxytocin and its receptor in connection with labour, birth, and skin-to-skin contact after birth in mothers and babies. However, some studies were identified that showed polymorphisms of the oxytocin receptor influenced the progress of labour. We also identified studies in which the level of global methylation was measured in vaginal birth and caesarean section, with conflicting results. Some studies identified differences in the level of methylation of single genes linked to various effects, for example, immune response, metabolism, and inflammation. In some of these cases, the level of methylation was associated with the duration of labour or mode of birth. We also identified some studies that demonstrated long-term effects of mode of birth and of skin-to-skin contact linked to changes in oxytocin function. CONCLUSION: There were no studies identified that showed epigenetic changes of the oxytocin system in connection with physiological birth. The lack of evidence, so far, regarding epigenetic changes did not exclude future demonstrations of such effects, as there was a definite role of oxytocin in creating long-term effects during the perinatal period. Such studies may not have been performed. Alternatively, the oxytocin linked effects might be indirectly mediated via other receptors and signalling systems. We conclude that there is a significant lack of research examining long-term changes of oxytocin function and long-term oxytocin mediated adaptive effects induced during physiological birth and skin-to-skin contact after birth in mothers and their infants.

Interacting With a Visiting Dog Increases Fingertip Temperature in Elderly Residents of Nursing Homes.

The aim of this study was to investigate whether interacting with a visiting dog influences fingertip temperature and cortisol levels in residents living in nursing homes for the elderly. The study included two groups, the dog group (n = 13) and the control group (n = 11-15) and lasted for 8 weeks for the dog group and 6 weeks for the control group. All participants were residents living at nursing homes for the elderly. The researchers visited small groups of the participants twice weekly during the entire study in both the dog and the control group. The visiting dog and the dog handler accompanied the researchers during weeks 3-6. Fingertip temperature was measured and saliva samples for cortisol determination were collected at 0, 20 and 60 min for the dog group and at 0 and 20 min for the control group. For analysis the study was divided into periods; Period 1 (week 1-2), Period 2 (week 3-4), Period 3 (week 5-6) and Period 4 (week 7-8, only the dog group). Mean values based on all data obtained at 0 and 20 min during period 1-3 were compared between groups. A second, separate analysis for the dog group also included data from 60 min and for period 4. For the dog group fingertip temperature increased significantly between period 1 and 2, 1 and 3 and 1 and 4 (p < 0.05). In addition, fingertip temperature rose significantly between 0 and 20 min and between 0 and 60 min within all periods. For the control group a significant decrease in fingertip temperature was observed between period 1 and 3 (p < 0.05). Fingertip temperature did not differ between the two groups during period 1, but was significantly higher for the dog group than for the control group during periods 2 and 3 (p < 0.05 and p < 0.001, respectively). Cortisol results are only presented descriptively due to that many samples had too low volume of saliva to be analyzed. In the present study interaction between elderly residents and a visiting dog resulted in increased fingertip temperature, probably reflecting a decrease in the activity of the sympathetic nervous system and therefore a decrease in stress levels.

Maternal plasma levels of oxytocin during breastfeeding-A systematic review.

INTRODUCTION: Oxytocin is a key hormone in breastfeeding. No recent review on plasma levels of oxytocin in response to breastfeeding is available. MATERIALS AND METHODS: Systematic literature searches on breastfeeding induced oxytocin levels were conducted 2017 and 2019 in PubMed, Scopus, CINAHL, and PsycINFO. Data on oxytocin linked effects and effects of medical interventions were included if available. RESULTS: We found 29 articles that met the inclusion criteria. All studies had an exploratory design and included 601 women. Data were extracted from the articles and summarised in tables. Breastfeeding induced an immediate and short lasting (20 minutes) release of oxytocin. The release was pulsatile early postpartum (5 pulses/10 minutes) and coalesced into a more protracted rise as lactation proceeded. Oxytocin levels were higher in multiparous versus primiparous women. The number of oxytocin pulses during early breastfeeding was associated with greater milk yield and longer duration of lactation and was reduced by stress. Breastfeeding-induced oxytocin release was associated with elevated prolactin levels; lowered ACTH and cortisol (stress hormones) and somatostatin (a gastrointestinal hormone) levels; enhanced sociability; and reduced anxiety, suggesting that oxytocin induces physiological and psychological adaptations in the mother. Mechanical breast pumping, but not bottle-feeding was associated with oxytocin and prolactin release and decreased stress levels. Emergency caesarean section reduced oxytocin and prolactin release in response to breastfeeding and also maternal mental adaptations. Epidural analgesia reduced prolactin and mental adaptation, whereas infusions of synthetic oxytocin increased prolactin and mental adaptation. Oxytocin infusion also restored negative effects induced by caesarean section and epidural analgesia. CONCLUSIONS: Oxytocin is released in response to breastfeeding to cause milk ejection, and to induce physiological changes to promote milk production and psychological adaptations to facilitate motherhood. Stress and medical interventions during birth may influence these effects and thereby adversely affect the initiation of breastfeeding.

Oxytocin's anti-inflammatory and proimmune functions in COVID-19: a transcriptomic signature-based approach.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic, infecting over 16 million people worldwide with a significant mortality rate. However, there is no current Food and Drug Administration-approved drug that treats coronavirus disease 2019 (COVID-19). Damage to T lymphocytes along with the cytokine storm are important factors that lead to exacerbation of clinical cases. Here, we are proposing intravenous oxytocin (OXT) as a candidate for adjunctive therapy for COVID-19. OXT has anti-inflammatory and proimmune adaptive functions. Using the Library of Integrated Network-Based Cellular Signatures (LINCS), we used the transcriptomic signature for carbetocin, an OXT agonist, and compared it to gene knockdown signatures of inflammatory (such as interleukin IL-1ß and IL-6) and proimmune markers (including T cell and macrophage cell markers like CD40 and ARG1). We found that carbetocin's transcriptomic signature has a pattern of concordance with inflammation and immune marker knockdown signatures that are consistent with reduction of inflammation and promotion and sustaining of immune response. This suggests that carbetocin may have potent effects in modulating inflammation, attenuating T cell inhibition, and enhancing T cell activation. Our results also suggest that carbetocin is more effective at inducing immune cell responses than either lopinavir or hydroxychloroquine, both of which have been explored for the treatment of COVID-19.

How much synthetic oxytocin is infused during labour? A review and analysis of regimens used in 12 countries.

OBJECTIVE: To compare synthetic oxytocin infusion regimens used during labour, calculate the International Units (IU) escalation rate and total amount of IU infused over eight hours. DESIGN: Observational study. SETTING: Twelve countries, eleven European and South Africa. SAMPLE: National, regional or institutional-level regimens on oxytocin for induction and augmentation labour. METHODS: Data on oxytocin IU dose, infusion fluid amount, start dose, escalation rate and maximum dose were collected. Values for each regimen were converted to IU in 1000ml diluent. One IU corresponded to 1.67µg for doses provided in grams/micrograms. IU hourly dose increase rates were based on escalation frequency. Cumulative doses and total IU amount infused were calculated by adding the dose administered for each previous hour. Main Outcome Measures Oxytocin IU dose infused. RESULTS: Data were obtained on 21 regimens used in 12 countries. Details on the start dose, escalation interval, escalation rate and maximum dose infused were available from 16 regimens. Starting rates varied from 0.06 IU/hour to 0.90 IU/hour, and the maximum dose rate varied from 0.90 IU/hour to 3.60 IU/hour. The total amount of IU oxytocin infused, estimated over eight hours, ranged from 2.38 IU to 27.00 IU, a variation of 24.62 IU and an 11-fold difference. CONCLUSION: Current variations in oxytocin regimens for induction and augmentation of labour are inexplicable. It is crucial that the appropriate minimum infusion regimen is administered because synthetic oxytocin is a potentially harmful medication with serious consequences for women and babies when inappropriately used. Estimating the total amount of oxytocin IU received by labouring women, alongside the institution's mode of birth and neonatal outcomes, may deepen our understanding and be the way forward to identifying the optimal infusion regimen.

Birth as a neuro-psycho-social event: An integrative model of maternal experiences and their relation to neurohormonal events during childbirth.

BACKGROUND: Psychological aspects of labor and birth have received little attention within maternity care service planning or clinical practice. The aim of this paper is to propose a model demonstrating how neurohormonal processes, in particular oxytocinergic mechanisms, not only control the physiological aspects of labor and birth, but also contribute to the subjective psychological experiences of birth. In addition, sensory information from the uterus as well as the external environment might influence these neurohormonal processes thereby influencing the progress of labor and the experience of birth. METHODOLOGY: In this new model of childbirth, we integrated the findings from two previous systematic reviews, one on maternal plasma levels of oxytocin during physiological childbirth and one meta-synthesis of women´s subjective experiences of physiological childbirth. FINDINGS: The neurobiological processes induced by the release of endogenous oxytocin during birth influence maternal behaviour and feelings in connection with birth in order to facilitate birth. The psychological experiences during birth may promote an optimal transition to motherhood. The spontaneous altered state of consciousness, that some women experience, may well be a hallmark of physiological childbirth in humans. The data also highlights the crucial role of one-to-one support during labor and birth. The physiological importance of social support to reduce labor stress and pain necessitates a reconsideration of many aspects of modern maternity care. CONCLUSION: By listening to women's experiences and by observing women during childbirth, factors that contribute to an optimized process of labor, such as the mothers' wellbeing and feelings of safety, may be identified. These observations support the integrative role of endogenous oxytocin in coordinating the neuroendocrine, psychological and physiological aspects of labor and birth, including oxytocin mediated. decrease of pain, fear and stress, support the need for midwifery one-to-one support in labour as well as the need for maternity care that optimizes the function of these neuroendocrine processes even when birth interventions are used. Women and their partners would benefit from understanding the crucial role that endogenous oxytocin plays in the psychological and neuroendocrinological process of labor.