Oxytocin and the augmentation of labor

OXYTOCIN AND THE AUGMENTATION OF LABOR

Human and Medical Perspectives

Peter Cur t i s University of North Carolina

At least a th i rd of the women g iv ing b i r th in the Uni ted States receive in t ravenous oxytocin for the induc t ion and augmenta t ion of labor. The p rob lem of inact ive or ineffect ive labor remains a major cha l lenge for b i r th at tendants , midwives , and phys ic ians who practice obstetr ics . Be- fore the d iscovery of oxytocin, t r ad i t iona l approaches to augmenta t ion ranged from magical and folk in te rvent ions to extensive b lood le t t i ng . Despi te its w ide use the effect iveness of oxytocin augmenta t ion has not been wel l s tud ied , and current research raises new ques t ions about i ts effect on the bra in .

KEY WORDS: Oxytocin; Augmenta t ion ; Labor; Obstetr ics.

The human female, from the momen t of her birth being des t ined . . . to the exclusive wretchedness of chi ldbear ing and the endurance of more suffering than human nature seems capable of sustaining, it behooves us to act in every instance with feeling, human i ty and tenderness .

Andrew Blake. Aphorisms Illustrating Natural and Difficult Cases of Accouchement (London, 1817)

Original version dated July 1991; revised version dated August 1993.

Address all correspondence to Peter Curtis, Department of Family Medicine, University of North Carolina, Chapel Hill, NC 27599-7595.

Copyright �9 1993 by Walter de Gruyter, Inc. New York Human Nature, Vol. 4, No. 4, pp. 351-366. 1045-6767/93/$1.00 + .10

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352 Human Nature, Vol. 4, No. 4, 1993

In the past few years the role of oxytocin in the induction and augmentation of labor has been reappraised. On the one hand there has been a realization that oxytocin dosage rates and increments have been exces- sive and may have led to increased fetal compromise and obstetric interventions (American Council of Obstetricians and Gynecologists 1978, 1987; Curtis and Safransky 1988; Seitchik et al. 1985) while on the other hand proponents of the active management of labor can point to aggressive amniotomy and high dose augmentation protocols with outcomes (short labors and low cesarean section rates) substantially better than most other reported data. Yet even when identical or similar protocols are used, major variations in outcomes are apparent in different countries and even within the same country. Few obvious reasons, such as ethnicity, teenage pregnancy, or nulliparity, appear to account for these differences (Lumley 1988). In a recent text specifically based on evidence culled from valid scientific studies, Kierse (1989) notes that augmentation of labor "is a subject that has largely been neglected by controlled research." He goes on to say that most of the current recom- mendations for the use of oxytocin are based on flimsy evidence. How- ever, the value of new augmentation policies, protocols, or methods is difficult to establish since important morbidities or complications occur so rarely that costly multicenter clinical trials involving large numbers of women are required to prove their effectiveness.

While oxytocin and its effect on the uterus have been preoccupying physicians and midwives, the neurobiologists have become increasingly interested in the effects of the hormone on the brain. It is now well established that oxytocin has effects in many parts of the brain and that its activity may be concerned with maternal behavior and bonding (Uvnas-Moberg 1989). Whether the synthetic hormone produces similar effects is not known.

From my perspective as a generalist clinician who has practiced in two different health care systems and worked with midwives in the home and specialists in the tertiary care center, the time is ripe for another look at oxytocin and its role in the birthing process. In this paper I pay particular attention to aspects of augmentation before and after the discovery of oxytocin as well as implications of the emerging ideas about its psychological effects.

THE PRE-OXYTOCIN ERA

The management of laborious, ineffective, or prolonged labor has re- mained a major challenge for birth attendants and obstetricians of all hues for centuries. The National Center for Health Statistics (National

Oxytocin and the Augmentation of Labor 353

Natality Survey 1980) reported that 31% of pregnant women required oxytocin for induction and augmentation. Recently reported rates of oxytocin use of augmentation in primigravidae range from 5% (Bidgood and Steer 1987) to more than 40% (Turner et al. 1988) in different institutions. One may wonder how it is that women and their accoucheurs managed labor relatively well before the discovery and use of oxytocin.

Early approaches to difficult labor were often based on magical concepts in which the baby could be "drawn" or persuaded to come out. Specific activities that would parallel the mechanics of the birth process were performed by others in the household (Frazier 1960). A number of these approaches are summarized in Table 1. Other methods were more directly applied to the reproductive organs. For instance, the Ebers papyrus recommended anointing the genitalia with henna and inserting into the vagina a mixture of fennel, incense, garlic, sert juice, salt, and wasp dung. In the time of Hippocrates, irritating powder was blown into the parturient's nose, a technique still used in late nineteenth century America and called "snuffing" or "quilling" because goose quills were used to blow the snuff into the patient 's nose (Murphree 1969; Speert 1973).

Blocked or prolonged labor was believed to be relieved by magical or superstitious actions by those close to the laboring woman, or by ap- peasing or fooling the gods responsible for the problem (Perret 1879). In Greek mythology, Lucina (with some help from Diana and Pallas) pre- sided over weddings and births. Alcmena was responsible for obstruct- ing or stopping labor and kept Hercules from popping out for seven days by sitting cross-legged. It was only when she told that he had just been delivered that she got up . . . and so let him out!

In the early nineteenth century, bloodletting became an important technique of accelerating labor in obstetric practice. In America, Ben- jamin Rush and his protegee Will Dewees were fearless bloodletters and recommended the intermittent bleeding of 30 to 40 ounces from an upright woman in labor--until she fainted. The woman was thus relieved of pain and often delivered the baby while unconscious (Siddall 1980). This treatment was based on Denman's proposition that pregnancy was almost always associated with plethora resulting from the reten- tion of menstrual blood (i.e., no menses for nine months of pregnancy )~a morbid condition relieved only by blood loss.

Changing maternal positions has been and continues to be used extensively in an attempt to improve both contractility and progress in labor (Fenwick 1987). Over the centuries a wide range of culturally specific positions has been used by different ethnic groups (Ploss et al. 1935). These varying postures have become less and less valued with the


Table 1. Augmentation of Labor

Concepts/Myths Actions in Labor

Transfer of male power

Baby irritated or drawn to come out

Direct massage of uterus through abdomen

Homeopathic similarity to delivery

Raising intra-abdominal pressure

Shaking baby loose

Supernatural help Spell or conjure

Inanimate power

Eliminating congestion

Direct action on uterus

Connection of breast to uterus

Uterine responses to herbs and oxytocics

Male partner lies with woman Woman wears partner's hat (Murphree 1968) Man's hat placed on abdomen (Witkowski

1844) Woman wears partner's clothes (Artschwanger

1982) Mother drinks foul tea (Artschwanger 1982) Woman squats or kneels over smoke or

fumigant; guns are fired; lodestone used to pull baby out; chairs rattled (Mackenzie 1927)

Kneading, applying binders, pounding massage (Artschwanger 1982; Witkowski 1844)

Loosening clothes, opening all doors and locks, unleashing animals (Mackenzie 1927; Ploss et al. 1935)

Sniffing, quilling, forcing candle or hair down throat (Murphree 1968; Stevenson 1920; Witkowski 1844)

Hippocratic succussion, "Son of a gun" (Campbell 1956; Speert 1973; Wilde 1849)

Religious/magical incantations; put silver coins/ herbs in the bed; tie knots on the abdomen; put "letters to God" (Himmelbriefe) under the pillow (Forbes 1966; Ploss et al. 1935)

Drink wine with amber/ebony (loosening stone); place eagle stone (hematite) on abdomen; tie diamond, jasper, or jade to shoulder and then to the thigh to draw baby out (Culpepper 1765; Levret 1776)

Enemas, bloodletting (Moreau 1839; Ramsbotham 1844; Siddal 1980)

Vibration of cervix, douches, drugs, herbs, galvanic shocks to abdomen, vaginal conductor (Ramsbotham 1844; Simpson 1855)

Nipple stimulation, breastfeeding (Curtis et al. 1986; Simpson 1855)

Ergot, cinnamon, borax, cannabis, mugwort, trillium, Ura Ursi (Culpepper 1765; Curtis et al. 1986; Simpson 1855; Weiner 1980:70--181)

adven t of m o d e r n obstetrics. The effective use of posi t ioning is n o w hardly taught to physicians training in obstetrics, w h o p re sumab ly m u s t rely on oxytocin. The skills of managing labor by modi fy ing mate rna l


position remain the purview of the midwife. The left lateral position, used to modify the size of the pelvic cavity when descent of the baby's head is slow or to help correct an occipito posterior position, was introduced in England in 1751 by Brudenhall Exton. Known as the London position, it quickly became fashionable not only because it was effective but also because it was less embarrassing than other postures. The French named it pudibonderie Britannique, a sardonic comment on the reluctance of English mothers and their accoucheurs to look at one another (Jameson 1938). This perspective continued with vigor into the Victorian era. In the mid-nineteenth century, an editorial in the New York Medical Gazette noted, "No indelicate exposure will be permitted, catheterism, vaginal exploration, delivery by forceps . . . can all be performed by a competent man as well without eye as with it: and by touch alone, beneath the ordinary covering, the whole art and mystery of the accoucheur can be acquired" (Medical News and Library 1850).

A wide range of herbs has been used not only as applications to the genitalia and vagina but as oral medications. Some were applied exter- nally because of the magical concepts that the herbal principle would reach the uterus and some were ingested because of their effect on bowel function (and thereby the uterus). For instance, castor oil was routinely used for this purpose until the late 1960s in England. Other herbs produced vomiting or sneezing, effects based on the mechanistic concept of "shaking up" the uterus. On the magical side for instance, the use of tea made from a mud dauber's nest in south Florida may have been based on a similarity of the emergence of the insects from their tubes to that of the fetus emerging from the vagina (Artschwanger 1982).

Herbs were the precursors of certain tried and true medications that became established in the early nineteenth century. Those that were believed to have an established effect on uterine inertia were ergot, alcohol, strychnine, and quinine (Ehrenfest 1913). As a result of the research on the actions of ergot, a marked contractile response of the uterus to intravenous posterior pituitary extract had been reported, and by 1916 this substance was used to accelerate labor when contractions were feeble; in patients with mild disproportion; to induce labor; in placental bleeding; and during cesarean section to prevent blood loss. It was hailed as the most important innovation in midwifery since the introduction of antisepsis. However, side effects included tetanic uterine contractions, vertigo, tachycardia, and uterine rupture, with fetal death occurring in 12% of cases (Sogolow 1964). In the 1940s, Eastman (1947) compared labor outcomes in two five-year periods with and without the use of pituitary extract. There was an 80% reduction in midforceps deliveries and a 30% reduction in cesarean sections. By 1950


Hellman, Harris, and Reynolds had developed and implemented the technique of intravenous infusion of pituitary extract, creating the first of many chains that have tethered the modern laboring woman to her bed.

OXYTOCIN

In 1951, pure oxytocin was isolated by the Nobel prize winner DuVig- neaud and then synthesized commercially in 1955. Its pharmacological effect was found to be equivalent to pituitary extract, and it was used initially in the form of buccal or sublingual tablets and later as a nasal snuff (Hendricks and Gabel 1960). In a monograph on oxytocin, Caldeyro-Barcia and Sereno (1961) noted that uterine effects were fully developed after 20 to 40 minutes of application of the drug, and the recommended dose rate for induction and augmentation of labor was between 1 and 2.5 mU/minute. Theobald (1983) reported on the outcomes of 5581 women, of whom 27% had amniotomy (rupture of the membranes) followed by oxytocin infusion--an approach very similar to the active management program currently being debated. Sixty percent of the women delivered in 12 hours and 88% delivered with a dose no more than 5 mU/minute. Partly as a result of another s tudy reporting shorter labors and no increase in adverse effects with high-dose, high- frequency oxytocin (Toaff et al. 1978), dosages increased significantly to 40 mU/min (ACOG 1978; Barber et al. 1972; O'Driscoll et al. 1973). In addition, the intervals at which the doses were incremented were re- duced to 15 or 10 minutes. These protocols were based on the under- standing that oxytocin has a half life in the bloodstream of 5-10 minutes. In a retrospective study on the dangers of oxytocin-induced labor, Lis- ton and Campbell (1974) divided subjects into low-dose (<32mU/min) and high-dose (>32mU/min) groups. Their s tudy and others continued to show that high-dose oxytocin was associated with high-frequency uterine contractions and greater incidence of fetal stress (Curtis and Safransky 1988). Also, at this time concern was raised regarding the possibility that high-dose oxytocin in labor (in doses greater than 20mU/ min) was a factor in the causation of hyperbilirubinemia (DiSouza et al. 1979).

In recent years, careful studies using computerized intrauterine pressure analysis have shown that (1) a steady-state plasma concentration of oxytocin is attained at about 40 minutes so the dose only needs to be increased if there is an inadequate uterine response after 30 to 40 minutes (Seitchik et al. 1985; Foster et al. 1989); (2) every uterus has its own optimal level of activity (this suggestion is based on the stable phase


hypothesis of Steer et al. 1985) above which increased doses of oxytocin have little effect other than to produce incoordinate action (Brindley and Sokol 1989); (3) low doses appear to be perfectly effective in achieving adequate contractions, as shown 30 years earlier by Theobald (1961); and (4) uterine response to oxytocin depends on preexisting levels of uterine activity and on the sensitivity of the uterine muscle rather than on standard doses of the drug. In other words, unlike most medications for which standard regimens have been developed for the general population, each woman has an unique and highly variable response to oxytocin (Bidgood and Steer 1987). The management of augmentation must therefore involve the careful observation of uterine contraction frequency, duration, and strength in conjunction with observation of fetal well- being (heart rate) and cervical dilation (Hauth et al. 1986).

How then can one reconcile the success of the active management of labor in producing low cesarean section rates in a few obstetric centers that use high-dose oxytocin when most high-dose protocols have been associated with frequently diagnosed dystocia and double-digit cesarean section rates? I believe that the interplay of five factors contributes to the confusing outcomes of these various regimens: (1) oxytocin dosage levels and increments (i.e., high dose vs. low dose; rapid vs. slow increments), (2) type of fetal monitoring (invasive intrauterine vs. intermittent external), (3) personal labor support (intense and continuous vs. intermittent and distant), (4) physician's behavior (technical vs. nurtur- ing), and (5) physician's skill in evaluating uterine contractions (casual vs. careful). Until prospective research studies and controls for these factors, we will remain unclear about the value of various augmentation methods and protocols. For example, there is no doubt that stress, anxiety, and fear play major roles in modifying and reducing uterine function (Cramond 1954; Crandon 1978; Henneborn and Cogan 1975; Kierse et al. 1989; Klaus et al. 1986). Anxiety, discomfort, or loss of individual control may occur with invasive monitoring, poor personal support during labor, and mechanistic physician behavior, which is the style of practice that has developed in the United States over the years. Together with a tradition of high-dose oxytocin and a lack of careful assessment of uterine contractility, this may be the basis for the high incidence of dystocia and cesarean sections (Brindley and Sokol 1989). On the other hand, the successful active management of labor developed by O'Driscoll and Meagher (1980) includes strict guidelines that a midwife or other medical support person must be with the laboring woman at all times---in other words, the woman is guaranteed that she will never be alone. This very different style of obstetric care, rather than amniotomy and uterine stimulation, may be the key factor in the low cesarean section rates. Thus, Thompson (1988) has shown that the mean


duration of labor in European hospitals is one hour less than in U.S. hospitals and that the reasons are more likely to be cultural or psycho- social than clinical. As stated by Caldeyro-Barcia and Sereno (1961), the uterus is very forgiving of oxytocin. Thus high or low dosage rates may not be dangerous in an environment of support and enthusiasm, but other factors such as an adverse birth setting or physician style of practice might trigger either uterine irritability or unnecessary interventions.

High-dose and rapid-increment protocols have continued in some obstetric practices in spite of changed guidelines recommending low- dose protocols (ACOG 1987). On the horizon is a more physiological approach to augmentation using pulsed doses, which replicate the natural two to three spurt secretions every 10 minutes. Early studies of the induction and augmentation of labor show that pulsed infusion was just as effective and lowered the total dose of oxytocin administered to 20% of the dose administered under continuous infusion. There was only a 10% incidence of uterine hyperstimulation compared with 60% in the continuous infusion group (Dawood 1989).

BREAST S T I M U L A T I O N AS A N A L T E R N A T I V E TO OXYTOCIN

The connection between suckling and uterine contractions in the imme- diate postpartum phase of parturition has been known at least since the time of Hippocrates (Adams 1849:746). The value of breast stimulation in the prepartum and intrapartum phases has been hardly mentioned in the medical and historical literature, though there are references to it in the anthropological literature (cf. Curtis et al. 1986). Early medical references alluded to the induction of labor by consensual breast stimulation (Merriman 1838) and by vesicants, cupping, and electric stimulation (Curtis et al. 1986). Occasional reports on breast stimulation by self- massage or pinching the nipples, or with a breast pump, to induce or augment labor began to be published in the 1950s. Different authors reported success rates of more than 70% (Jhirad and Vago 1973; Leinzinger and Rainer 1954; Salzmann 1971). None of these were randomized controlled trials, so the data were suspect. In her 1978 book on spiritual midwifery, Gaskin reported the use of breast simulation to promote uterine contractions. Perhaps because of these purely descriptive data or because of the possibility of embarrassment in performing this technique, there was no evident interest or further investigation of this phenomenon until Freeman et al. (1982) suggested that breast stimulation might prove a low-cost, low-technology alternative to oxytocin infusion for fetal stress testing to assess uteroplacental insufficien-


cy. Breast-stimulated contraction stress tests (BS-CST) are now widely used the United States. The rationale for the method was based on the milk ejection reflex--receptors in the breast respond to suckling pressure, warmth, and touch to stimulate oxytocin secretion by the neuro- hypophysis, thereby provoking both milk ejection and uterine contractions (Poulain and Wakerley 1982). In randomized controlled trials the technique was found to be effective in ripening the cervix in postmature women and in inducing labor (Chayen et al. 1986; Salmon et al. 1986).

Our own work on augmentation of labor using this technique was triggered by observation of its apparent effectiveness in women with ruptured membranes who were either not in active labor or not pro- gressing. For many of these women it offered the option of participating in the management and control of their own labor. Early descriptive data indicated that 75% of women using breast stimulation proceeded to normal delivery, whereas the remainder required additional oxytocin. Encouraged by these results, we undertook a clinical trial to compare breast stimulation with oxytocin, hypothesizing that it would be as effective and safe. Our (unpublished) data show that only 35% of women proceeded to a spontaneous delivery with breast stimulation alone, the remainder switching to oxytocin either at their own request or because of the obstetrician's decision. Unfortunately the s tudy population was too small to show any significant differences in the cesarean rates. Cesarean section rates for nullipara were 17% for breast stimulation subjects and 24% for women receiving oxytocin.

This result was very disappointing, given the encouraging findings of earlier pilot studies, and we wondered how it could be explained. A survey of the nursing and medical staff undertaken at the beginning of the study suggested that several factors might have contributed to the lack of effectiveness of breast stimulation. First, for both nurses and physicians, nearly half felt that breast stimulation was likely to be embarrassing and that women would not be willing to use the technique. Second, the study population consisted of nonprivate patients from a poor socioeconomic background. Many had no support person with them. Third, the physicians, consisting of both residents and attending physicians, were extremely busy and often brusque, with little time for patients. Given the anecdotally reported reticence or shyness of women in certain cultural groups in dealing with breastfeeding issues and the unsupportive environment of the labor suite, we believe that the effectiveness of breast stimulation (as well as oxytocin) was significantly inhibited by maternal stress (Commentary in Birth 1989; Newton 1987; Odent 1984). Thus, whether in a context of active management of labor using amniotomy and oxytocin or in situations involving breast stimulation, it appears that maternal comfort and a supportive, low-anxiety environment are prerequisites to uncomplicated labor. It would be use-


ful to establish the validity of breast stimulation in promoting uterine contractions not only because this technique is much used by midwives but also because it has considerable potential as a low-cost intervention for both inadequate labor and postpartum hemorrhage in third world countries.

PSYCHOLOGICAL EFFECTS OF OXYTOCIN

Although Newton (1973) described oxytocin as the "hormone of love" some years ago, neuroendocrinological research has only recently opened up a new perspective on the role that it may play in mental health (Pedersen et al. 1988). Oxytocin, first described as originating in the posterior pituitary gland, is also found in several other areas of the brain, the cerebrospinal fluid, ovaries, testes, and adrenal tissue (Gan- ten and Pfaff 1986). Intracerebral injections of high doses of oxytocin in virgin rats produce maternal behavior, and the use of an oxytocin antagonist delays this behavior in lactating rats. There is increasing evidence that oxytocin regulates behavioral reactions. For instance, oxytocin neurotransmitters are implicated in the growth of tolerance for and dependance on opiate analgesics and in control of alcohol and cocaine addiction in experimental animals (Pedersen et al. 1988). While prolactin has been associated with protective (and often aggressive) behavior, oxytocin is associated with interactive behaviors as well as suppressing memory (perhaps accounting of the distancing of labor pain memories in the post partum phase of pregnancy). These central effects are strong- ly influenced by estrogen, which activates prolactin and oxytocin receptors accounting for different behaviors in the various stages of parturition (Uvnas-Moberg 1989). Bonding behavior that occurs immediately post partum can be enhanced by a rise in oxytocin associated with breastfeeding one hour after delivery. High oxytocin levels have also been correlated to personality characteristics, such as social dependency and indirect aggression (Uvnas-Moberg 1989). What is not known is the degree to which blood levels of oxytocin reflect hormonal activity in the brain, and if they do, whether infusion of oxytocin administered either continuously or pulsed and used to augment labor has a direct effect on the woman's emotional state.

SUMMARY

Kierse (1989) reports that labor augmentation rates vary from 5 to 40% depending on the institution and country involved. He noted that few


data support the liberal use of oxytocin. Instead, measures to improve the environment of labor and give the woman freedom to move around and be comfortable may be just as effective. Although the trend is now for low dose-slow increment protocols, it is likely that earlier high-dose therapy without careful supervision has accounted for inappropriate interventions with consequent high cesarean section rates. Yet a high- dose protocol in an intensely supervised and supportive environment has been associated with extremely low cesarean section rates. A highly supportive labor setting with the continuous presence of a health professional are significant factors that must be studied as potential major contributors to the reduction of cesarean section rates. Breast stimulation, as a technique of augmentation, conceptually fits well into the natural birth process, but it requires further validation from both the effectiveness and the safety perspectives. However, multicenter studies would be required to achieve adequate sample sizes in order to demon- strate its effect. Politically and culturally this type of study might not be attractive to funding institutions.

Oxytocin, originally thought to be associated only with breastfeeding and uterine contractility, may turn out to be one of the major actors in modifying human behavior, particularly emotional interactive pattern- ing. One of the fascinating questions for the future may be, what are we doing to the minds of up to 40% of women in labor who receive oxytocin infusions?

Peter Curtis is a professor in the Department of Family Medicine at the University of North Carolina at Chapel Hill. He is also Director of Fellowships and Director of the Institute for the Generalist Physician. His interests include low back pain, alternative medicine, cervical cancer, and human papiilomavirus.

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Oxytocin and the augmentation of labor

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