Maternal plasma levels of oxytocin during physiological childbirth – a systematic review with implications for uterine contractions and central actions of oxytocin

Background:Oxytocin is a key hormone in childbirth, and synthetic oxytocin is widely administered to induce orspeed labour. Due to lack of synthetized knowledge, we conducted a systematic review of maternal plasma levelsof oxytocin during physiological childbirth, and in response to infusions of synthetic oxytocin, if reported in theincluded studies.Methods:An a priori protocol was designed and a systematic search was conducted in PubMed, CINAHL, andPsycINFO in October 2015. Search hits were screened on title and abstract after duplicates were removed (n=4039), 69 articles were examined in full-text and 20 papers metinclusion criteria. As the articles differed in designand methodology used for analysis of oxytocin levels,a narrative synthesis was created and the material wascategorised according to effects.Results:Basal levels of oxytocin increased 3–4-fold during pregnancy. Pulses of oxytocin occurred with increasingfrequency, duration, and amplitude, from late pregnancy through labour, reaching a maximum of 3 pulses/10 mintowards the end of labour. There was a maximal 3- to 4-fold rise in oxytocin at birth. Oxytocin pulses also occurred inthe third stage of labour associated with placental expulsion. Oxytocin peaks during labour did not correlate in timewith individual uterine contractions, suggesting additional mechanisms in the control of contractions. Oxytocin levelswere also raised in the cerebrospinal fluid during labour, indicating that oxytocin is released into the brain, as well asinto the circulation. Oxytocin released into the brain induces beneficial adaptive effects during birth and postpartum.Oxytocin levels following infusion of synthetic oxytocin up to 10 mU/min were similar to oxytocin levels inphysiological labour. Oxytocin levels doubled in response to doubling of the rate of infusion of synthetic oxytocin.Conclusions:Plasma oxytocin levels increase gradually during pregnancy, and during the first and second stages oflabour, with increasing size and frequency of pulses of oxytocin. A large pulse of oxytocin occurs with birth. Oxytocin inthe circulation stimulates uterine contractions and oxytocin released within the brain influences maternal physiologyand behaviour during birth. Oxytocin given as an infusion does not cross into the mother’s brain because of the bloodbrain barrier and does not influence brain function in the same way as oxytocin during normal labour does