Effect of Acupuncture on Induction of Labor

Transcription

1 THE JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE Volume 15, Number 11, 2009, pp ª Mary Ann Liebert, Inc. DOI: =acm Effect of Acupuncture on Induction of Labor Chi Eung Danforn Lim, M.B.B.S., 1 Jenny M. Wilkinson, Ph.D., 2 Wu Shun Felix Wong, M.D., 3 and Nga Chong Lisa Cheng, M.B.B.S. 4 Abstract Objective: The objective of this study is to review the existing scientific evidence on the potential role of acupuncture on induction of labor during pregnancy. Design: The Medline, EMBASE, Cochrane Central Register of Controlled Trials, AMED (Allied and Complementary Medicine), and NCCAM (The National Center for Complementary and Alternative Medicine) databases were searched to identify relevant monographs from 1970 to Inclusion criteria: These criteria included all available human acupuncture studies on pregnant women carrying a viable fetus due for third trimester induction of labor. Exclusion criteria: These criteria included studies not meeting the inclusion criteria, in languages other than English, or animal studies. Results: Ten (10) studies on labor induction were identified. The duration of labor as a result of acupuncture treatment ranged from 10 hours 20 minutes to 29.1 hours. All of the studies demonstrated labor induction by acupuncture treatment. However, because two randomized controlled trials reported that there was no statistically significant effect of acupuncture, these results are more suggestive than definitive. Furthermore, although the relationship between cervical ripening and interleukin-8 (IL-8), prostaglandin F 2a (PGF 2a ), and b-endorphin is well documented in the literature, there is no evidence to suggest that acupuncture alters these mediators. Serum levels of IL8, b-endorphin, and PGF 2a were not found to be significantly influenced by acupuncture. Conclusions: Although the definitive role of acupuncture in inducing labor is still yet to be established, the existing studies suggest that acupuncture may be beneficial in labor induction. Further randomized clinical trials are needed to investigate this further. Introduction Current Western medical intervention of labor induction is not without criticism. As was evident from the literature, there are many documented side-effects (for example, prolonged labor, failed induction, and delivery by cesarean section with increased morbidity 1,2 related to the therapies employed to address the labor induction). The success of these therapies in inducing labor varies greatly and needs to be weighed against the risk of potential side-effects. The potential risk of fetal harm side-effects from conventional medical treatment of labor induction contributed greatly to the rationale of many of the researchers who embarked on research into the area of acupuncture in the treatment of labor induction. Traditional Chinese medicine (TCM) is a system of medicine based on ancient Chinese philosophy and includes a number of diagnosis and therapeutic techniques, one of which is acupuncture. Acupuncture has been applied as a therapeutic medical technique for more than 2000 years in China, although there is evidence of acupuncture pre-dating this in other medical systems. 3 Acupuncture needling involves inserting a fine sterile needle into the skin at an acupoint and manipulating the needle using a range of different manual methods in order to enhance the stimulation to the specific acupoint. Acupuncture is growing in popularity in Western countries. 4 Fisher, 5 for example, found that 12% 19% of individuals in a European population had received acupuncture treatment, and Allaire 6 showed that in the United States state 1 Division of Chinese Medicine, Royal Melbourne Institute of Technology University, Bundoora Campus, Victoria, Australia. 2 School of Biomedical Sciences, Faculty of Science, Charles Sturt University, Boorooma, New South Wales, Australia. 3 School of Women s and Children s Health, Faculty of Medicine and 4 Sydney Children s Hospital, Faculty of Medicine, University of New South Wales, Sydney, Australia. 1209

2 1210 LIM ET AL. of North Carolina, 20% of 82 midwives interviewed reported using acupuncture for cervix ripening and labor induction. Xue et al. 7 reported that 68.9% of the Australian population had used complementary and alternative medicine, with 9.2% of individuals having used acupuncture. Burke et al. 8 carried out a National Health Interview Survey crosssectional study in United States and stated that 4.1% of the respondents reported lifetime use, and 1.1% (representing 2.13 million Americans) reported recent use of acupuncture. Acupuncture has been described as an effective tool for cervical ripening and induction of labor. 9 In contrast, Lyrenas et al. 10 reported that acupuncture was neither sufficient to reduce the need for analgesics nor to reduce the duration of labor. However, other authors have observed significant effects of acupuncture on the duration of the first and second stages of labor. 9,11 15 This article provides a descriptive and critical review of the current research available on acupuncture in the English literature regarding the induction of labor. The objective of this article is to evaluate the effectiveness of acupuncture on labor induction and to discuss the proposed mechanisms of how acupuncture influences labor. Hopefully, we will also determine whether there is sufficient evidence to suggest that this ancient method may be valuable in labor induction, or may need further clinical research. Materials and Methods A comprehensive search of literature that was published from 1970 to 2008 was undertaken using the following keywords: Acupuncture, Traditional Chinese Medicine, Labor Induction, and Pregnancy. These terms were used to search the follow databases: Medline (PubMed), EMBASE, Cochrane Central Register of Controlled Trials, AMED (Allied and Complementary Medicine), and NCCAM (The National Center for Complementary and Alternative Medicine) databases. Additional articles were also identified from the reference list of identified articles. Each located article was reviewed, and those describing animal studies or that did not include acupuncture were discarded. Using this method, 10 studies were identified and were assessed according to the following criteria: effect to initiate labor, effect on interleukin 8 (IL-8), prostaglandin F2a (PGF 2a ), b-endorphin, and use of acupuncture prescription. Data were independently extracted by 2 authors (DL and LC) using a piloted data extraction form. Data on study characteristics including methods, participants, interventions, and outcomes were extracted. The selected trials that claimed to be randomized were retrieved and judged as adequately randomized if they meet the set criteria by Jadad 16 (1996). Another 2 authors ( JW and FW) are responsible for systematic review dispute resolution for study selection, adequacy of treatment, and revision and review of final interpretations of findings. The data retrieval process is shown in Figure 1. Results Acupuncture with and without electrical stimulation was used to induce labor in pregnant women in 10 studies meeting the inclusion criteria (Table 1). The common points that are stated in the literature to induce labor are Hegu (LI4) 9,17 21 and Sanyinjiao (SP6). 9,13,17 21 Herder 22 first suggested the use of galvanic current for inducing labor in In 1959, Preisman and Ryskin 23 introduced the methods of inserting electrodes into the cervix for missed-abortion patients. Later in 1962, Theobald and Lundborg reported a 70% success rate by using the electrodes to stimulate the cervix for inducing labor. Sawasaki and Fujimoto 24 reported a 71.6% success rate of labor induction by placing electrodes onto the lower-pole cervix. Theobald 25 conducted the first controlled study utilizing electrical current to stimulate the abdominal wall skin for labor induction with 27 subjects receiving the treatment while 102 subjects served as controls. Seventy-seven percent Potential studies identified from the databases by using keywords of acupuncture, Traditional Chinese Medicine, labour induction, pregnancy, human studies Twelve studies identified include both randomized controlled study, nonrandomized noncontrolled study and nonrandomized controlled study Ten studies were recruited Two studies were excluded (one in German and the other in French) Data extraction was performed by 2 authors and RCT was assessed by the criteria set by Jadad et al. 33 FIG. 1. Data retrieval process flow chart.

3 EFFECT OF ACUPUNCTURE ON INDUCTION OF LABOR 1211 (77%) of participants in the treatment group delivered 4 days before the estimated date of delivery, while only 46% of participants in the control group delivered within that time range. Tsuei 17 reported that 10 of 12 subjects who received acupuncture and electrical stimulation to the upper and lower limbs developed favorable uterine contractions and softening of the cervix after treatment. On the other hand, Tsuei 7 also reported that a number of acupoints have effects to arrest labor and uterine contraction. In the 1970s, four studies reported the use of acupuncture for inducing labor. 9,17,18,26 In particular Yip 26 has utilised electro-acupuncture which was reported to be successful in inducing 21 women (out of 31) of gestational age of 38 to 42 weeks. Tsuei 17 reported a success rate of 83% on inducing labor in 12 pregnant women with pregnancy duration ranging from 19 to 43 weeks. The average labor time in this study was 13.1 hours. Tsuei 9 reported a 78% success rate on inducing labor by utilizing electro-acupuncture on 41 subjects (34 term and post-term women and 7 pregnant women with intrauterine fetal death). There were no known teratogenic effect or side-effects reported from these studies. Theobald 25 and Kubista et al. 18 attempted to elucidate the effect of acupuncture and labor induction on term pregnancy by carrying out nonrandomized trials. Theobald 18 applied electrodes to four selected acupoints to stimulate the abdominal wall skin as the treatment group and reported that 77% (20 of 27 subjects) delivered 4 days prior to the estimated date of delivery. In the control group with no electrical stimulation, only 46% of subjects had delivery 4 days prior to the estimated date of delivery. Kubista et al. 18 used electro-acupuncture on 35 pregnant women and compared the outcomes with a control group of 35 subjects. Eightyeight percent (88%) of subjects (31 pregnant women) in the treatment group reported an increased intensity of uterine contractions compared to the control group, where no increase in uterine contraction intensity was observed. Five (5) randomized controlled studies 13,14,19 21 with Jadad score 3=5 were identified in this review. However, only one study 20 reported statistically significant results while others 14,21 found a decrease in time between prelabor rupture of membrane to active phase of labor, but the results were not statistically significant. Dunn 13 performed the first randomized controlled study using acupuncture to induce labor. However, the subject size was small, with only 10 women in each arm of the study. Rabl 19 recruited 45 subjects (20 control, 25 acupuncture), for a randomized controlled study; however, the results were inconclusive. Gaudernack s 14 study demonstrated that the labor time in the treatment group was shortened and statistically significant ( p ¼ 0.027). In addition, the acupuncture group was shown to request fewer oxytocins infusions to induce uterine contraction during labor ( p ¼ 0.018). The results obtained from this study supported the positive role of acupuncture as an effective treatment in labor induction. In contrast to the studies performed by Dunn s 13 and Rabl s 19 groups, Gaudernack 14 was able to recruit 91 subjects for the study, with 43 receiving acupuncture treatment. The randomized controlled studies that Harper s 20 and Selmer-Olsen s 21 teams carried out were able to demonstrate that the subjects in the acupuncture treatment group have a shorter active phase of labor. However, neither study showed a statistically significance difference between control and acupuncture groups. Selmer-Olsen s 24 team used the largest sample size (101 subjects with 53 allocated to control group) of all randomized control trials completed on this topic, and all subjects received treatment depending on their Chinese medicine syndrome differentiation and were thus treated using different acupuncture points. Discussion The findings of the research papers reviewed suggest that acupuncture may stimulate the onset of labor, with all the preliminary findings demonstrating some positive effects in reduction of labor duration. However, most of the sample sizes in the studies are too small to draw definitive conclusions. In the absence of a sound research design, a control group, adequate sample size, randomization, and appropriate statistical analysis, these findings may not be as convincing as they first appear. It is imperative that further research be undertaken to determine whether there is in fact a causal relationship between the changes observed and the acupuncture treatment. Acupuncture rationale and needling details The acupoints that were chosen in the reviewed studies (Table 2) included SP6, LI4, GV1, GB34, 9 SP6, LV3, 13 GV7, HT7, PC6, 15 LV3, ST36, and CV4. 14 Selmer-Olsen et al. 21 applied CV4 as universal point by adding other points depending on the subject s individual TCM syndrome differentiation. Among these points, SP6 and LI4 are the points that have the indication for inducing labor according to the classic TCM literature. According to Deadman et al. 27 in the Manual of Acupuncture, Sanyinjiao SP6 is the meeting point of the three yin channels of the leg (Spleen, Liver, and Kidney) and is one of the most important and widely used of the acupuncture points. The three leg yin channels dominate menstruation, conception, pregnancy, leukorrhea, and the external genitalia. SP6 is the single most important distal point in the treatment of any gynecologic, obstetric, or postpartum disorder whether characterized by deficiency of qi; Blood; yin, yang, or Kidney essence; failure of Spleen qi to hold the Blood; or stagnation of qi, Blood, Dampness, Damp Heat, or Phlegm. 27 SP6 is also an essential point to induce labor, assist in transverse presentation, and alleviate the pain of childbirth. 27 Hegu (LI4) has a strong action on promoting labor as well. According to the Ode to Elucidate Mysteries, Xu Wen-bai has used the combination of reducing Zusanli ST36 and reinforcing Hegu LI4 for inducing a twin birth. Due to its strong action of inducing labor, and even promoting the expulsion of a dead fetus, Hegu LI4 is considered to have an indication of labor induction. It is also important to note that despite certain acupoints being used in some studies (e.g., GV1, GV7, PC6, HT7, LV4, GB34) do not have the proven indication on labor induction, 27 they were applied either as a control protocol or as additional points for different Chinese medicine syndrome differentiation at the studies. Mechanism The duration of labor following the acupuncture that is reported in the literature ranged from 10 hours 20 minutes 17 to 29.1 hours 14 ; however the mechanism by which acupuncture

4 Table 1. Summary of Research Journal Articles Identified Authors And year Research design Sample size Control group Results Discussion & general comment Tsuei et al Nonrandomized trial without control group Kubista Nonrandomized trial et al with control group Yip et al Nonrandomized trial without control group Tsuei et al Nonrandomized trial without control group Dunn et al. Randomized controlled trial ( Jadad score 3=5) Tempfer Matched pair study et al with control group Rabl et al Randomized controlled trial ( Jadad score 3=5) Gaudernack Randomized controlled et al trial ( Jadad score 3=5) Harper et al. Randomized controlled trial ( Jadad score 3=5) Selmer-Olsen Randomized controlled et al trial ( Jadad score 3=5) 12 No control group used The average duration for labor by using acupuncture is about 10 hours gravidae with intact membranes with no electro-acupuncture performed 31 cases evidenced certain increase in the intensity of labor contraction frequency 31 No control group used The pattern of uterine contractions induced in the subjects was similar to that in normal labor 60 No control group used 78% success rate for labor induction subjects received a placebo treatment, in which the equipment was attached but not activated women who gave birth during the same period and did not receive acupuncture treatment were matched for age and parity out of 45 allocated in control group out of 91 allocated in control group out of 56 allocated in control group out of 101 allocated to control group in term pregnancy, post-term pregnancy and intrauterine fetal death 90% of experimental subjects showed an increase in contractions after stimulation, compared with 30% in control group Serum level of IL-8, PGF2a, and b-endorphin were not significantly correlated with the duration of the 1 st and 2 nd stage of labor The time period from expected date of confinement to delivery was on average 5 days in the acupuncture group and 7.9 days in the control group The time from PROM to delivery was 29.1 hrs compared to 32.7 hrs in control group. Significant reduction of oxytocins infusion in need for the acupuncture group. Subjects in acupuncture group delivered 21 hrs sooner than the subjects in control group The median time from PROM to onset of active phase of labor in the acupuncture group vs. control group were 15 vs hrs, respectively, but no statistically significant difference noted The results may not be truly indicative of effectiveness and differences in the treatments Relative small sample size and non-rct study It was unable to be concluded whether the labor induction effect was caused by the electroacupuncture alone or the amniotomy No further details can be obtained with regard to this study Electrical stimulated acupuncture has evident effect of initiating uterine contractions in certain acupoints. This study represent some possible links in between acupoints to autonomic nervous system. The evidence that strong contractions are produced suggest that labor induction may be possible by this method, but this study has not established such an outcome and the sample size is rather small The results support the role of acupuncture as an effective treatment. The prenatal acupuncture treatment has a role of reducing the duration of labor. However, serum levels of IL-8, PGF 2a, and b-endorphin were not influenced by acupuncture, and are thus likely to mediate acupuncturerelated effects during labor The results are not conclusive and only provide little support to the previously known evidence from other studies The shortening of labor time in treatment group was statistically significant. The use of acupuncture is associated with a significant reduction of oxytocin infusion in need to augment labor. The results support the role of acupuncture as an effective treatment. The results of the trial revealed no statistically significant effect of acupuncture in reducing labor time Relative small sample size The results of the trial revealed no statistically significant effect of acupuncture in reducing time from PROM to active phase of labor when comparing treatment group to control group RCT, randomized controlled trial; IL-8, interleukin-8; PGF2a, prostaglandin F2a; PROM, premature rupture of membranes.

5 EFFECT OF ACUPUNCTURE ON INDUCTION OF LABOR 1213 Study Table 2. Summary of Acupoints Applied in the Research Journal Articles Identified Acupoints Tsuei et al SP 6 & LI 4 Kubista et al SP 6 & LI 4 Yip et al Not specified Tsuei et al SP 6 & LI 4 or GV 1 & GB 34 Dunn et al SP 6 & LV 3 Tempfer et al GV 20, HT 7 & PC 6 Rabl et al SP 6 & LI 4 Gaudernack et al ST 36, LV 3 & CV 4 Harper et al LI 4, SP 6, BL 31 & 32 Selmer-Olsen et al CV 4 for all subjects; SP qi deficiency group: BL 20, SP 6, ST 36 LV qi stagnation group: BL 18, LV 3, LI 4 KI deficiency group: BL 23, KI 3 Other points: GV4, GV20, HE7, BL15, LU7, BL32, PC6, SJ6 induces labor is unclear. Liao et al. 28 suggested that acupoint stimulation may increase discharge from thalamic nuclei and also the hypothalamic anterior pituitary system. This is supported by the work of Gaudernack et al., 14 who found that subjects in the acupuncture treatment group required significantly less oxytocin to stimulate uterine contraction during labor. Tempfer et al. 15 hypothesized that acupuncture has a neuronal stimulation component that may increase the contractility of the uterus without influencing locally active factors (e.g., IL-8 and PGF 2a ) either by central oxytocin release or by parasympathetic stimulation of the uterus. It seems that close to term, stimulation of the parasympathetic system excites the uterus, whereas sympathetic stimulation might be excitatory or inhibitory. 29 The clinical process of cervical ripening is characterized by an intense remodeling of the cervical connective tissue. After an increase of vascularization, water uptake, content of collagen, proteoglycans, and heparin sulphate in the connective tissue during pregnancy, the onset of cervical dilatation is characterized by enzymatic degradation of cervical connective tissue. 30 This is in part mediated by neutrophil granulocytes, accumulated in the cervix due to the chemotactic activity of the leukotriene IL-8. Barclay et al. 31 reported that the cervix has the ability to produce large amounts of IL-8, and that cervical dilatation is inducible by local injection of IL-8 in an experimental setting. In addition to IL-8, several other factors have been described to be critically involved in cervical ripening. Prostaglandins (e.g., PGF 2a) have been described to continuously rise during labor activity and to play a key role in the initiation and regulation of uterine activity during parturition. 32 b-endorphin, secreted by the pituitary gland, placenta, and various other organs, rises with progressive cervical dilatation, shows a positive correlation with pain intensity during labor, and has been shown to be a genuine part of the endocrine response to the stress of parturition. 33 These acupuncture studies do not demonstrate any relation between the chemical mediators IL-8, PGF 2a, and b- endorphin. Tempfer et al. 15 demonstrated that the serum levels of IL-8 and PGF 2a did not differ significantly between the two groups of subjects (pregnant women received acupuncture treatment versus match-controlled subjects without receiving acupuncture treatment) in their study. A minority of research articles addressed the proposed mechanism of the action of acupuncture related to labor induction. In three studies, 9,17,26 the majority of post-term pregnant women began labor during the treatment, though this often took more than 12 hours. The selected acupoints may be activating afferent nerve fibers and influencing hormonal changes through the ascending pathways to the hypothalamus, or reflex activation of autonomic efferents to the uterus. Alternatively, it may because of a commonality of the spinal cord segment of the parasympathetic outflow and the spinal reference of the acupuncture point selected for treatment. The exact mechanism of the action of acupuncture on this system is still not known. Conclusions From the critical review of the literature associated with acupuncture on labor induction, it was evident that there was an extremely low incidence of side-effects associated with acupuncture. There were no adverse effects of acupuncture noted or reported in the studies identified in this review in relation to the delivery outcome. Acupuncture may offer a safe, low-risk, nonteratogenic alternative treatment for labor induction. There is suitable justification for a well-designed clinical trial to investigate the use of acupuncture on labor induction, based on the observational data that acupuncture has potentially positive outcomes demonstrated from the literature on inducing labor contraction. In addition, there are benefits of having relative low-risk=no side-effects observed from the acupuncture treatment compared to the side-effects associated with the routine Western medical treatments documented in the literature. Thus, further research is needed to investigate the suggested positive effect of acupuncture treatment on labor induction. This will also aid the clinicians and women who seek acupuncture treatment alongside conventional obstetrics in the decisionmaking process. Disclosure Statement No competing financial interests exist. References 1. Turnbull AC, Anderson AB. Induction of labor. J Obstet Gynaecol Br Commonwealth 1979;75: Clinch J. Induction of labor: A six-year review. Br J Obstet Gynaecol 1979;75: World Health Organisation, Regional Office for the Western Pacific, Guidelines for Clinic Research on Acupuncture, WHO Regional Publication, Western Pacific Series No. 15. Manila, Philippines, MacLennan AH, Wilson DH, Taylor AW. Prevalence and cost of alternative medicine in Australia. Lancet 1996;347: Fisher P, Ward A. Complementary medicine in Europe. Br Med J 1994;309:

6 1214 LIM ET AL. 6. Allaire AD, Moos M, Wells SR. Complementary and alternative medicine in pregnancy: A survey of North Carolina nurse-midwives. Obstet Gynaecol 2000;95: Xue CCL, Zhang AL, Lin V, et al. Complementary and alternative medicine use in Australia: A national populationbased survey. J Altern Complement Med 2007;13: Burke A, Upchurch DM, Dye C, Chyu L. Acupuncture use in the United States: Findings from the National Health Interview Survey. J Altern Complement Med 2006;12: Tsuei JT, Lai Y, Sharma SD. The influence of acupuncture stimulation during pregnancy: The induction and inhibition of labor. Obstet Gynecol 1977;50: Lyrenas S, Lutsch H, Hetta J, et al. Acupuncture before delivery: Effect on pain perception and the need for analgesics. Gynecol Obstet Invest 1990;29: Kubista E, Jucera H. Acupuncture preparation of primigravidae as a means of shortening labor. Wilen Klin Wochenschr 1973;85: Hyodo M, Gega O. Use of acupuncture anesthesia for normal delivery. Am J Chin Med 1977;5: Dunn PA, Rogers D, Halford K. Transcutaneous electrical nerve stimulation at acupuncture points in the induction of uterine contractions. Obstet Gynecol 1989;73: Gaudernack LC, Forbord S, Hole E. Acupuncture administered after spontaneous rupture of membranes at term significantly reduces the length of birth and use of oxytocin: A randomized controlled trial. Acta Obstet Gynecol Scand 2006;85: Tempfer C, Zeisler H, Heinzl H, et al. Influence of acupuncture on maternal serum levels of interleukin-8, prostaglandin F2 alpha, and beta-endorphin: A matched pair study. Obstet Gynecol 1998;92: Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Controlled Clin Trials 1996;17: Tsuei JT, Lai Y. Induction of labor by acupuncture and electrical stimulation. Obstet Gynecol 1974;43: Kubista E, Kucera H, Muller-Tyl E. Initiating contractions of the gravid uterus through electroacupuncture. Am J Chin Med 1975;3: Rabl M, Ahner R, Bitschnau M, et al. Acupuncture for cervical ripening and induction of labor at term: A randomized controlled trial. Wien Klin Wochenschr 2001;113: Harper TC, Coeytaux RR, Chen W, et al. A randomized controlled trial of acupuncture for initiation of labor in nulliparous women. J Maternal Fetal Neonat Med 2006;19: Selmer-Olsen T, Lydersen S, Mørkved S. Does acupuncture used in nulliparous women reduce time from prelabour rupture of membranes at term to active phase of labour? A randomised controlled trial. Acta Obstet Gynecol Scand 2007;86: Herder RT, Simpson JT. Historical review of British obstetrics and gynaecology. Kerr JM, Johnston RW, Phillips MH, eds. Edinburgh: Livingstone, Preisman AB, Ryskin FE. Electrical stimulation in late miscarriage. Zdravookhranenie Turkmenistana 1959;2: Sawasaki C, Fujimoto Z. Labour induction by the electric stimulation apparatus. Sanfujinka no Jissai 1966;15: Theobald GW. The Electrical Induction of Labour. London: Butterworths, Yip S, Pang J, Sung M. Induction of labour by acupuncture electro-stimulation. Am J Chin Med 1976;4: Deadman P, Al-Khafaji M, Baker K. A Manual of Acupuncture. London: Journal of Chinese Medicine Publications, Liao Y, Seto K, Saito H, et al. Effect of acupuncture on adrenocortical hormone production: Variation in the ability for adrenocortical hormone production in relation to the duration of acupuncture stimulation. Am J Chin Med 1979;7: Bell C. Autonomic nervous control of reproduction: Circulatory and other factors. Pharmacol Rev 1972;24: Chwalisz K, Benson M, Scholz P, Daum J. Cervical ripening with the cytokines interleukin 8, interleukin 1 beta and tumour necrosis factor alpha in guinea pigs. Hum Reprod 1994;11: Barclay CG, Brennand JE, Kelly RW, Calder AA. Interleukin- 8 production by the human cervix. Am J Obstet Gynecol 1993;169: Fairlie F, Phillips G, McLaren M, et al. Uterine activity in spontaneous labor and maternal peripheral plasma prostaglandin E2 and F2 alpha metabolites. J Perinatal Med 1993; 21: Bacigalupo G, Riese S, Rosendahl H, Saling E. Quantitative relationships between pain intensities during labor and beta endorphin and cortisol concentrations in plasma: Decline of the hormone concentrations in the early postpartum period. J Perinatal Med 1990;18: Address correspondence to: Chi Eung Danforn Lim, M.B.B.S. Division of Chinese Medicine RMIT University, Bundoora Campus Bundoora, Victoria, 3083 Australia celim@unswalumni.com

7