Improving the Pitocin Conversation: One Question at a Time

July 12, 2013. Marta Wegorzewska, PhD candidate, in collaboration with Dr. Seth Bokser, MD. Edited by Dr. Tracey McLean, MD*.

Two women arrive to the hospital ready for the moment they have been preparing for months. Each woman has a plan for what she wants. One woman goes into labor so quickly there is no time for an epidural. Aware of her low threshold for pain, she never imagined delivering without pain medication. Yet, a healthy and happy Emily is born. Across the hall, 10 hours of painful labor results in little progress. An exhausted and frightened mother, who hoped to deliver without any medical intervention, wants options. Physicians have to make a difficult decision: wait longer or intervene. 12 hours into her slow progressing labor, physicians and mother decide to augment the delivery of the baby with a drug called Pitocin, a synthetic form of the natural hormone Oxytocin. Mother and baby are carefully monitored. Pitocin triggers contractions and a relieved mother starts to progress in labor. Baby Jacob is ready to be born. Suddenly, the doctors notice that Jacob’s heartbeat is slowing. Maybe they waited too long or maybe the contractions were too strong. The removal of Pitocin does not change Jacob’s state and doctors make the decision to perform a Cesarean Section (C-Section). Moments later, a happy and healthy Jacob is welcomed into the world.

When it comes to childbirth, every woman is different. Every experience is unique. Every delivery poses challenges for the mother, the baby, physicians and nurses. And every plan gets modified. Yet, the goal is the same: healthy mother, healthy baby. Mothers, fathers, family members, physicians and the public are questioning how this goal is being accomplished. Over 20% of deliveries are induced and Pitocin is the most common method used for labor induction 1. In this piece, we will explore the science behind labor and reveal what we know and are still learning about Pitocin.

Safety first: can Pitocin harm the baby?

Critics question the overuse and misuse of Pitocin. The documentary, The Business of Being Born, was released in 2008 to bring awareness to the safety concerns of critics 2. Today, Pitocin continues to be accused of being dangerous to mother and fetus. On May 7, 2013, new research on Pitocin was presented at the Annual Clinical Meeting of the American College of Obstetricians and Gynecologists (ACOG). The researchers claim to reveal, for the first time, adverse effects of Pitocin use on newborns. The Internet was quick to condemn Pitocin using little scientific data to base its claims. In fact, this study has yet to undergo a peer review process; a process put in place to determine the accuracy and quality of the data. Once the work led by Primary Investigator Michael Tsimis, MD, becomes published and available for the community to evaluate, only then will it be appropriate to judge the effect of Pitocin on the baby. Meanwhile, an already published study found no adverse affects on newborns after using a low dose of Pitocin but is limited by the small cohort of patients that were considered 3. Historically, research on Pitocin has been plagued by small sample sizes leading to questionable conclusions. There exists a consensus over the need for better data to learn more about Pitocin safety.

The recent findings discussed at the conference of ACOG on Pitocin shows that the concerns and questions surrounding Pitocin safety are not being ignored. In the press release put out by ACOG, Dr. Tsimis was quoted saying, “However, we don’t want to discourage the use of Pitocin, but simply want a more systematic and conscientious approach to the indications for its use.” Pitocin’s potential for effectiveness and safety should not be discouraged. But physicians and patients alike should demand better research with sound data to help define the parameters that make Pitocin safe.

Oxytocin and Pitocin: identical or fraternal twins?

Pitocin is made to mimic the natural occurring hormone Oxytocin that is produced throughout pregnancy and induces contractions at the time of labor. Despite the difference in their origin, Pitocin and Oxytocin are identical twins that look exactly alike 4. Pitocin is a synthesized drug that is a perfect replica of the natural hormone Oxytocin.

The rules of chemistry dictate that structure and function go hand in hand. If two chemicals look identical, they should act alike. But we all know that despite their appearance, identical twins have different personalities. Oxytocin and Pitocin are no exception. But not because chemistry got it all-wrong. In fact, Pitocin has the potential to function exactly like Oxytocin because they are structurally identical. However, replicating the naturally released concentrations of Oxytocin has proven a challenging feat. Various concentrations have been tried. Higher dosages of Pitocin compared to lower doses have been shown to cause stronger contractions in women being induced while resulting in fewer C-sections 5. While it is unclear if higher doses cause harm to the fetus, there is a lack of consensus about the optimal oxytocin dosage that should be used to ensure efficacy and safety 5,6. This lack of consensus comes from a difficulty in replicating the natural behavior of Oxytocin that is released from the brain in pulses and is eliminated from the circulation at a rapid speed 7. Better insight into the physiology of labor and behavior of Pitocin will help determine the optimal use of Pitocin to induce labor.

From fetus to baby: how is labor triggered?

For 80% of women, nine months of pregnancy ends with the natural delivery of a healthy baby 1. Uterine contractions increase in frequency and intensity resulting in a dilated cervix ready to allow passage of the baby through the birth canal. The amount of time it takes for the baby to be born from the start of labor (contractions begin) varies among women. For 20% of women, labor either does not begin or it stalls (cervical dilation does not progress despite contractions) 1. This great diversity in scenarios at the time of delivery begs the question: what triggers labor?

During pregnancy, Oxytocin is made in the brain and is released into the blood stream. The blood stream is a means of transportation. Ultimately, Oxytocin settles on one of the numerous oxytocin-binding receptors in the uterus. The interaction between oxytocin and its receptor causes contractions to begin. During labor, the sensitivity of the uterus to Oxytocin increases because the number of receptors available to interact with Oxytocin increases significantly 8. However, what signals the start of labor that results in this physiological change in the uterus is unknown. Maybe a mature fetus is able to communicate to the mother that its time to live outside the womb. A fetal lung protein released during the onset of labor has been proposed to trigger labor 9. Maybe the maternal immune system plays an active role in inducing labor. Immune cells that function to protect us during times of sickness are found in the uterus at the time of labor and may play a role in its onset 10. The lack of understanding of how labor is triggered makes it very difficult for physicians to predict when labor will happen and when it won’t. Which makes for difficult decision-making.

To wait or not to wait, that is the question!

Physicians assess risks and benefits when deciding to wait or intervene during labor. Sometimes patience ultimately leads to natural vaginal delivery and reduces unnecessary cesarean deliveries that pose a risk to maternal health 11. But waiting can also be problematic. Waiting too long leads to larger babies that are more difficult for the mother to deliver, in turn increasing the chances of C-section 12. The placenta, which functions to supply the fetus with nutrients and oxygen from the mother’s circulation, starts to age and become less efficient resulting in fetal malnutrition and deprivation of oxygen 13. Although low overall, the risk of fetal death increases with gestational age 14,15. Physicians face a challenging decision and must consider maternal and fetal health when determining if intervention outweighs the risk of waiting 16.

Answering questions with quality research

The implementation of a standardized protocol and careful monitoring of mother and baby during Pitocin administration was born out of research that aimed to address the concerns over Pitocin safety 17. These concerns are encouraging better quality scientific studies in obstetric care.

Scientists and physicians are improving the quality of the research needed to answer the question: does Pitocin harm the newborn? Often Pitocin is given to augment labor that stalls after many hours. In the previous section, we learned that prolonged labor has potential risks for the newborn. Therefore, a conclusion that Pitocin harms the baby without acknowledging that prolonged labor may also have an effect on the baby is questionable. Comparing prolonged, Pitocin-augmented labor to quick, Pitocin-free labor does not rule out if the effect on newborn health came from the many more hours of labor or from Pitocin. To address concerns over Pitocin safety, future studies need to ensure that the effect of prolonged labor does not confound data on Pitocin’s effect on newborn health. Scientists and physicians need to compare Pitocin-augmented mothers to mothers who had long labor but were not given Pitocin. Although challenging due to how rare the latter scenario is, it is the most accurate comparison for defining Pitocin’s effect on newborn health.

Understanding what triggers normal labor and how these triggers fail in some women will also help ensure Pitocin safety but providing better indicators for Pitocin use. Until science figures out why some women require medical intervention, expectant parents should discuss their plan with their healthcare providers to prepare for a delivery that may not go according to that plan. Education of, and communication among, providers and their patients will encourage appropriate use of Pitocin while ensuring the careful monitoring of mother and baby when Pitocin becomes the agreed-upon, best option for helping achieve a safe delivery of a healthy baby.

*Conflict of interest: The authors have declared that no conflict of interest exists.

This post is checked by the following science articles:
1) Martin A, Hamilton B, Ventura S, Osterman M, Wilson E, Matthews TJ. Births: Final data for 2010. Natl Vital Stat Rep. 2012;61(1):1.
2) The Business of Being Born. Dir. Abby Epstein. Perf. Mary Helen Ayres, Julia Barnett Tracy, Sylvie Blaustein. New Line, 2008. Film.
3) Bugg G, Siddiqui F, Thornton J. Oxytocin versus no treatment or delayed treatment for slow progress in the first stage of spontaneous labour. Editorial Group: Cochrane Pregnancy and Childbirth Group Published Online: 6 JUL 2011.
4) Stewart R and Slezak R. Synthetic and Natural Oxytocin: Comparison of their effects in initiating labor. Obstetrics and Gynecology. 1958; 11(3):295.
5) Wei SQ, Luo ZC, Qi HP, Xu H, Fraser WD. High-dose vs low-dose oxytocin for labor augmentation: a systematic review. Am J Obstet Gynecol. 2010 Oct;203(4):296-304.
6) Alfirevic Z, Kelly AJ, Dowswell T. Intravenous oxytocin alone for cervical ripening and induction of labour. Cochrane Database Syst Rev. 2009.
7) Meyer C, Freund MM, GuerneY, Richard P. Relationship between oxytocin release and amplitude of oxytocin cell neurosecretory bursts during suckling in the rat. J Endocrinol 114: 263–270, 1987.
8) Kimura T, Tanizawa O, Mori K, Brownstein MJ, Okayama H. Structure and expression of a human oxytocin receptor. Nature 356: 526–529, 1992.
9) Condon JC, Jeyasuria P, Faust JM, Mendelson CR. Surfactant protein secreted by the maturing mouse fetal lung acts as a hormone that signals the initiation of parturition. Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4978-83.
10) Gomez-Lopez N, Vega-Sanchez R, Castillo-Castrejon M, Romero R, Cubeiro-Arreola K, Vadillo-Ortega F. Evidence for a role for the adaptive immune response in human term parturition. Am J Reprod Immunol. 2013 Mar;69(3):212-30.
11) Dana E.M. Henry, Yvonne W. Cheng, Brian L. Shaffer, Anjali J. Kaimal, Katherine Bianco, Aaron B. Caughey. Perinatal Outcomes in the Setting of Active Phase Labor Arrest. Obstet Gynecol. 2008 Nov; 112(5): 1109–1115.
12) Najafian M, Cheraghi M. Occurrence of FetalMacrosomia Rate and ItsMaternal and Neonatal Complications: A 5-Year Cohort Study. ISRN Obstet Gynecol. 2012;2012:353791.
13) Vorherr H . Placental insufficiency in relation to postterm pregnancy and fetal postmaturity. Evaluation of fetoplacental function; management of the postterm gravida. Am J Obstet Gynecol. 1975;123(1):67.
14) Bruckner TA, Cheng YW, Caughey AB. Increased neonatal mortality among normal-weight births beyond 41 weeks of gestation in California. Am J Obstet Gynecol. 2008;199(4):421.e1.
15) Yudkin PL, Wood L, Redman CW. Risk of unexplained stillbirth at different gestational ages. Lancet. 1987 May 23;1(8543):1192-4.
16) ACOG Practice Bulletin No. 107: Induction of labor. ACOG Committee on Practice Bulletins –Obstetrics. Obstet Gynecol. 2009;114(2 Pt 1):386.
17) Optimizing Protocols in Obstetrics. Oxytocin for Induction. ACOG.


One thought on “Improving the Pitocin Conversation: One Question at a Time

  1. What a great and easy to follow article on an unexpectedly interesting topic that I never thought I’d care to read about. I like the fact that this blog provides a layman’s exploration behind common medical events like migraines and childbirth. I foresee this developing into something like the science version of NPR’s Planet Money which I absolutely love. Ever thought about doing a podcast?

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