Supporting a Physiologic Approach to Pregnancy and Birth: A Practical Guide

Section 1

Understanding a physiologic approach

Chapter 1

The case for a physiologic approach to birth: An overview

Melissa D. Avery

Childbirth is normal until proven otherwise.

Peggy Vincent

Picture yourself at a neighborhood clinic on a typical weekday. You are conducting a health care visit with a woman as her prenatal care provider; she is 32 weeks pregnant. You ask how she has been feeling—she is fine. Her fundal height is 33 cm, the baby feels vertex, fetal heart tones are 134 beats per minute, a 2-pound weight gain since her last visit. No, she has not experienced any bleeding or headaches, no contractions. Yes, she started prenatal classes this week and the instructor reviewed the signs of early labor. Transition to the hospital. You’re the nurse admitting a woman in labor to the birthing room with the bed centrally located, the fetal monitor in an attractive wood cabinet next to the bed. You ask when her contractions began, the current frequency and duration, and if her baby has been moving. Her membranes are intact, vital signs are normal, fetal heart rate 148. While you turn down the bedcovers, she changes into a hospital gown and asks if water birth is possible; she read about it on a pregnancy website and thought it might be a nice option.

On the face of it, the daily experiences of many maternity care clinicians and the women we care for seem pretty normal, routine, and positive to a degree. We talk about pregnancy as a normal life process, yet women enter our care system where problems are anticipated rather than emphasizing the normalcy of pregnancy. The number and ­frequency of technological interventions continue to increase while the outcomes of care have ­worsened, with some recent abatement. Substantial national resources are spent on what is supposed to be a normal process. From the clinic to the hospital, how do we as nurses, midwives, and physicians provide a safe and high-quality experience for the women we care for during pregnancy and birth? How are we helping women plan for and achieve their goals and desires for their birth experiences?

Cesarean section has become the most common operating room procedure in America [1]. The U.S. cesarean section rate is nearly 33%, appearing to at least stabilize in 2010 and 2011 after rising by 60% from 1996 to 2009 [2,3]. The Healthy People 2020 goal is a moderate 10% reduction in cesarean births to low-risk women (term, singleton, vertex) from a baseline of 26.5% in 2007 to 23.9% by 2020, as well as a 10% increase in vaginal births among women with a previous cesarean [4]. At the same time, infant mortality, a measure used worldwide to reflect care to mothers and families, is 6.05 deaths in the first year of life per 1,000 live births [5]. This is higher than all but three member countries of the Organisation for Economic Co-operation and Development (OECD), an organization of primarily developed countries including Europe, the United States, Canada, and others [6]. Infant mortality in the United States has declined from 6.71 per 1,000 live births in 2006 after remaining stable from 2000 to 2005 [7]. An 8% decline in premature births occurred from 12.80% in 2006 to 11.72% in 2011 [3], along with increased efforts at ­preventing early elective births such as the March of Dimes and the California Maternal Quality Care Collaborative [8,9]. Maternal mortality was 12.7 per 100,000 live births in 2007 [10], a number that may be increasing [11], with the U.S. rate behind forty-nine other developed nations in 2010 [12]. (See summary data in Table 1.1.)

Table 1.1 U.S. maternity care data.

Not readily apparent in these statistics are significant racial disparities. For example, infant mortality among African American women was 11.42 per 1,000 live births, 2.2 times greater than the 5.11 for White women [5]. Maternal mortality was approximately 3 times higher for African American women compared to White women [10,11]. These ­disparities are inexcusable in a country with such vast resources; we must reverse these trends by assuring access to continuous high-quality health care [13]. Returning to a more normal or physiologic approach to maternity care including access to ­comprehensive ­continuous care to all women in the United States is one step in that direction.

Spending and doing too much

Nearly 99% of U.S. births occur in hospitals [2], thus liveborn infant and pregnancy and childbirth are among the most common reasons for hospitalization [1], accounting for nearly a quarter of hospital discharges in 2008, and over $98 billion in hospital charges (amount hospitals bill for a stay). Medicaid payment covers the cost of care for over 40% of pregnancies and births [14]. Of pregnancy and childbirth and liveborn infant ­hospitalizations in 2008, $41 billion was paid by Medicaid and $50 billion was paid by private insurers [15]. The United States spent 17.6% of gross domestic product (GDP) on health care in 2010, more than any of the other OECD countries [6]. This phenomenon of doing more in perinatal care without a corresponding improvement in care outcomes was first referred to as the perinatal paradox more than 20 years ago [16]. Tremendous resources are allocated to maternal and infant care in the United States and yet our ­outcomes do not compare well with other developed countries. Although preterm birth has declined in recent years and the cesarean rate may have stabilized, there is much more work to be done.

The passage of the Affordable Care Act (ACA) in 2010 marked the first success in half a century of legislative attempts to change health care in the United States. When fully implemented, millions more Americans will have health care coverage. An important focus of the ACA is on improving health care and reducing costs by enhancing coordina­tion of care for individuals with chronic conditions, reducing medical errors, reducing ­hospital-acquired infections, and reducing waste in the system. Improving health care, improving care outcomes including client satisfaction, and providing care at lower cost, often referred to as the triple aim, are not only possible but necessary. In addition to improved access to health care, ACA improvements in care options for women include family planning and breast and cervical cancer screening without co-pays, coverage for maternity and newborn care, home-visiting services during pregnancy and early childhood, restricting insurance companies from charging women higher premiums than men, and enhanced support for breastfeeding mothers [17].

Concerns about the increased use of technology and medical intervention overuse in maternity care have been expressed by clinicians, scientists, educators, and others around the world. Multiple health professions and health-related organizations worldwide have issued statements calling for a more normal or physiologic approach to ­pregnancy and birth. Concerned with the rising rates of interventions in maternity care in the United Kingdom, the Maternity Care Working Party published a normal birth consensus ­statement in 2007, supported by the Royal College of Obstetricians and Gynecologists and the Royal College of Midwives, defining normal delivery as spontaneous labor, labor ­progression, and birth, without the use of interventions such as labor induction, epidural, cesarean section, and forceps. The statement proposes action steps to increase the proportion of normal births in the four UK countries [18]. Other statements, in some cases endorsed by multiple health professions organizations, have called for support of birth as a normal process, reduced intervention, use of best available evidence, and woman-­centered care [19–22]. More recently, in the United States, the American Academy of Family Physicians; American Academy of Pediatrics; American College of ­Nurse-Midwives; American College of Obstetricians and Gynecologists; American College of Osteopathic Obstetricians and Gynecologists; Association of Women’s Health, Obstetric and Neonatal Nurses; and Society for Maternal-Fetal Medicine endorsed a statement on quality patient care in labor and delivery identifying pregnancy and birth as normal processes requiring little if any intervention in most cases [23]. The authors called for effective communication, shared decision making, teamwork, and quality measurement in the provision of maternity care. Three U.S. midwifery ­organizations partnered in the development of a statement supporting physiologic birth—defining normal physiologic birth, identifying factors that disrupt and factors influencing normal birth, and proposing a set of actions to promote normal birth [24]. Reflecting the growing concern about the U.S. cesarean section rate, authors of a report summarizing a recent workshop held by the American Congress of Obstetricians and Gynecologists, the Society for Maternal-Fetal Medicine, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, plus a similar commentary, recommended specific practices and actions for clinicians and health systems to prevent the first cesarean section [25,26]. At least on paper, it seems as if we all agree.

Internationally, a series of normal labor and birth conferences have been held beginning in England in 2002 and most recently in China in 2012 [27]. The conferences highlight current research and best practices in promoting normal birth. In the United States, authors of a key report on evidence-based maternity care have identified induction of labor and cesarean section as overused procedures. Additionally, midwives, family ­physicians, and prenatal vitamins were described as underused interventions [28]. Following that report, Childbirth Connection, a nonprofit organization focused on improving maternity care, held a multistakeholder meeting focused on just how the quality and value of maternity care could be improved in the United States. The resulting Blueprint for Action: Steps toward a High-Quality, High-Value Maternity Care System provides clinicians, payers, educators, and care systems with excellent proposals to improve our care to women [29]. Strong Start for Mothers and Newborns, a federally funded program under the Centers for Medicare and Medicaid Services (CMS) Center for Medicare and Medicaid Innovation, has provided funding to reduce early elective births and to test new models of enhanced prenatal care to meet the triple aim. The models include enhanced prenatal care in group prenatal settings, in birth centers, and in maternity care homes [30].

In order to improve quality, health systems need to measure and report on the care provided [29,31,32]. Maternity care measures are available for use to improve quality such as the Joint Commission, the National Quality Forum, and the American Medical Association (AMA). The AMA Physician Consortium for Performance Improvement measure set was developed by an interprofessional work group and includes measures related to overuse of certain care practices as well as a measure for spontaneous labor and birth [33]. These quality measure sets are available to health systems, clinicians, and payers to improve care and achieve better care outcomes. In addition to the national ­measure sets, a tool to examine the optimal processes and outcomes of normal ­pregnancies among groups of women has been developed and tested. The Optimality Index-US ­measures what is optimal or best possible care processes and outcomes—within a ­philosophy of aiming for the best outcome using the least number of interventions [34–36]. Higher Optimality scores in one setting over another may reflect an ­environment that supports a low intervention and physiologic approach to prenatal and labor care. Available as a research tool, clinicians can also use the index to examine institutional care processes and in peer review and other quality improvement processes [35].

Looking for something different

Women have signaled that they are beginning to look for something different, evidenced by the recent increase in out-of-hospital births [37]. After declining since 1990, home births increased by 29% from 2004 to 2009 [38]. In 2010, the increase in both home and free-standing birth center births was large enough to cross the 99% mark, documenting more than 1% of births occurring outside the hospital [2]. While the absolute number may not seem impressive (47,000 of nearly 4 million), the change is a message that a ­segment of the U.S. childbearing population is looking for something else. Birth is ­important to women, often a transformative event that they remember clearly throughout their lives. Many women believe labor and birth should not be interfered with and women understand their right to full information and to accept or refuse specific care processes [39]. Women are asking for specific services in hospitals such as water immersion, ­aromatherapy, and acupressure as part of the support tools available for labor and birth. Although epidurals remain popular, women are increasingly planning for an unmedicated birth and express a desire to be in control of their birth process [40]. The author of the 2011 consumer book Natural Birth in the Hospital: The Best of Both Worlds [41] reaches out to the nearly 99% of women giving birth in hospitals, letting them know that they, too, can have a more normal experience in a hospital and how to get what they want.

Women’s partnerships with their care providers are of utmost importance. Return for a moment to your clinic—sit down for a few more minutes with your client. What is it that she and her birth support persons really hope for during her labor and birth? What does the best evidence suggest are the preferred care measures resulting in the least harm? Take a little more time to engage in meaningful discussions with her so she puts aside her fears about labor, forgets the anxiety she’s seen in births depicted in the media, and partners with you in understanding options and planning for her labor and birth. When you welcome her to the hospital birthing room, tell her that your goal is to accommodate her and her partner’s preferences. Although it sounds easy, and most likely what we are trying to provide, current data support an alternate story.

This book can help you—the clinician at the bedside—take a look into the clinic exam rooms and hospital labor units to see what else is possible. The various chapter authors are clinicians and educators just like you. Together we have worked to summarize recent research and other published information and provide some ideas, tools, and ­solutions to put into the hands of maternity care clinicians including midwives, nurses, physicians, and others. The authors herein argue for supporting and enhancing women’s confidence in their ability to give birth. At the same time we aim to increase the confidence of care providers to trust in the normal process and support women expecting a healthy outcome rather than looking for reasons to disrupt the process. It goes without saying that specific conditions warrant medical intervention and higher levels of care such as ­pre-existing diabetes, hypertension, and multifetal gestation, and yet even women with those conditions can still be supported as mothers, enhancing normal or physiologic processes as much as possible.

A word about language. We have chosen to talk about an approach to physiologic ­pregnancy and birth with a profound respect for the intricate changes that occur during both pregnancy and labor that result in what is commonly referred to as the miracle of birth. We use the word birth in most cases, to honor the work that women do in giving birth. Delivery is retained in some circumstances, primarily to refer to women ­delivering their newborns. Normal is meant to signify the usual process of being pregnant and giving birth without being disturbed by technology or other interventions that are not necessary in supporting the usual processes [42], with no intent to judge any woman’s pregnancy or birth experience [43]. Every woman is unique; her process is also unique. Physiologic or normal is not just one variety or type, but each woman’s individual ­experience to be supported, managing only when the experience is truly outside the range of normal and thus requiring additional intervention. Even then, aspects of a normal or physiologic approach can be retained, always remembering the unique woman giving birth. Finally, this book is based on a belief that it takes all types of maternity care ­providers working in partnership to improve maternity care. Thus we refer to providers and clinicians, and the authors represent midwives, nurses, physicians, and others.

A look inside

Section 1 begins with a review of the normal physiologic changes of pregnancy as well as the physiologic uterine phases through pregnancy, labor initiation, continuation, and birth. Although the exact mechanism of the initiation of labor is not completely ­understood, the known components of pregnancy and labor physiology are fascinating, with increasing understanding through research on the intricacies of the labor process. With the goal of a physiologic approach as the norm, how do we adapt routine prenatal care to enhance women’s confidence and understanding of pregnancy as normal and not an illness to be treated? In a woman-centered approach, women are supported to understand the range of tools for comfort in early labor, how to recognize active labor and the best time to transition to the birthing unit (if not the home), and mechanisms to support the process. We work to bring women’s knowledge and understanding of the process as close to ours as possible and respect the knowledge and expertise each woman brings to her pregnancy. Originally proposed as a description of exemplary midwifery care, the art of doing ’nothing’ well [44] is recommended here as an approach for all clinicians providing maternity care unless there is a compelling reason to do something more.

Section 2 begins with a theoretical perspective on promoting comfort for women in labor followed by chapters describing integrative therapies for pregnancy, labor, and birth. Maternity care clinicians may not have sufficient knowledge and understanding about integrative or complementary and alternative medicine (CAM) practices [45]. Midwives appear to have a more positive view of the effectiveness of alternative therapies and are less likely to believe that results of CAM are due to placebo effect than ­obstetricians [46]. Researchers investigating nurse-midwives’ experiences with CAM therapies ­demonstrated that a majority of certified nurse-midwife respondents reported CAM use. Herbal preparations, pharmacologic/biologic, mind-body interventions, and manual healing/bioelectromagnetic therapies were used most often. Diet and lifestyle therapies were also common [47]. Women have increased their use of CAM therapies during pregnancy, thus maternity care providers need to become knowledgeable about these practices and facilitate communication, cooperation, and respect among alternative and conventional providers [48].

Within the context of promoting comfort, chapters on relaxation, touch therapies, water immersion and water birth, acupuncture and acupressure, and aromatherapy are offered as adjuncts to doing nothing in support of women during pregnancy, labor, and birth. While not an exhaustive representation of possible integrative therapies, reviews of ­evidence and practical suggestions are offered as tools for maternity care clinicians to assist women in achieving their preferred birth experience. Authors aim to help clinicians understand these therapies better, including specific instructions on how to use certain techniques, as well as information on referring to providers of the therapy and how specific practices, such as acupuncture, are regulated.

Finally, section 3 focuses on the broader care and education systems. Individual clinicians can provide excellent one-on-one care and effect local change. In order to change maternity care in the United States, we must also work within our broader systems to shift to a more physiologic approach. Because nearly 99% of births occur in hospitals, the best opportunity to effect meaningful system change is to adjust the approach to care on labor units. Nurses are key in making that happen, and a group of labor nurses have proposed a possible solution after examining available evidence and related information. The other 1% of births occur outside the hospital; evidence supports the safety of this approach for carefully selected women when out-of-hospital practice is imbedded in a broader system of consultation and referral to more intensive care when needed. Respecting out-of-­hospital birth as a safe environment for low-risk women who desire that care is critical. When transfer to the hospital setting is required, the process of transfer and receiving the woman and her family can be more seamless and positive with enhanced understanding and respect among clinicians from both settings.

For the change we desire to be permanent and system-wide, we must promote ­interprofessional collaborative practices that are built on a foundation of mutual trust and respect, with care decisions made by informed women and their families [23,24,49,50]. Maternity care providers must be educated together so that they will provide the seamless quality care women deserve, with clinical education occurring in environments where students learn with interprofessional care teams. Policy changes to support clinicians practicing together to the full extent of their education and training, in an environment where all women have access to quality health care, is the final critical component to improving maternity care. Legislators and policy-makers need to hear from their constituent clinicians in making those necessary changes.

National attention is focused on maternity care in a way that has not been seen in recent history, providing an opportunity to be transformative [29]. This group of authors, representing committed clinicians, educators, and researchers from multiple ­professions, invites you to come along on a journey to serve women today to build ­tomorrow’s healthier families. Women and their families deserve the very best that we can collectively provide in an environment that respects pregnancy and birth as normal processes, that respects the women and their families/support networks to lead their care, and where we respect and trust each other as partners in providing excellent care. The change required is larger than any one clinician or profession can accomplish. Indeed, we are encouraged that health professionals are responding to calls for interprofessional ­practice and education. While we add our voices to the larger discussions in Congress, federal health-related agencies, educational settings, and corporate boardrooms, a more quiet yet powerful change can occur in our care settings through the ­conversations and plans we make with each other and with our clients every day—clinic by clinic, woman by woman, birth by birth.

References

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49. Waldman RN & Kennedy HP. (2011). Collaborative practice between obstetricians and ­midwives. Obstetrics & Gynecology, 118, 503–504.

50. Avery MD, Montgomery O, & Brandl-Salutz E. (2012). Essential components of successful collaborative maternity care models: The ACOG-ACNM Project. Obstetrics and Gynecology Clinics of North America, 39, 423–434. DOI: 10.1016/j.ogc.2012.05.010.

Chapter 2

The physiology of pregnancy, labor, and birth

Cindy M. Anderson

Key points

The placenta is the interface between the mother and fetus supporting perfusion to meet fetal growth and development needs; transport is influenced by placental area, diffusing distance, permeability of placental barrier, and maternal-fetal blood flow in the intervillous spaces.

The placenta assumes the neuroendocrine functions that are regulated in the nonpregnant state by the typical hypothalamus-pituitary-end organ feedback mechanisms.

Progesterone is the dominant hormone during pregnancy, its inhibitory effects largely responsible for the uterine quiescent phase during pregnancy.

To meet the increased demand for maternal and fetal oxygen and oxygen transport during pregnancy, cardiac output, oxygen consumption, and left ventricular stroke volume increase, along with a 40% increase in blood volume primarily comprised of the plasma component. Maternal pulmonary tidal volume and inspiratory capacity increase while residual volume, expiratory reserve volume and functional residual capacity decline.

Changes in the firm cervical structure to more pliable and distensible occur in later pregnancy as water concentration increases relative to collagen, resulting from an increase in highly hydrophilic glycoaminoglycans such as chondroitin sulfate and hyaluronan.

The complex signaling between mother, placenta, and fetus that triggers labor initiation and progression are not completely understood, however likely involve the interplay among hormonal, mechanical, and immune factors.

The transition from progesterone dominance in the uterine quiescent phase to the estrogen dominance in the activation phase stimulates coordinated, synchronous contractions in myometrial cells in the contractile fundus. Uterine contractions are promoted by increased myometrial oxytocin receptors and increased prostaglandin production in the fetal membranes.

Stress and anxiety during labor can be exacerbated by fear, thus triggering cognitive pain perception and increasing sensitivity to pain.

[I]t is time that professionals regain their trust in the physiology which enables healthy women to labour and deliver, mostly without interference.

Marianne Mead

Introduction

The processes of the initiation and progression events characteristic of the intrapartum period are critically important for optimal care of pregnant women, yet the underlying mechanisms of labor physiology are poorly understood. The physiologic changes of pregnancy are necessary to prepare women for the unique challenges brought on by the significant demands placed on multiple maternal body systems, required to support ideal function of the maternal-placental-fetal unit. The intrapartum period presents new challenges associated with unique adaptations associated with initiation and progression of labor, culminating in birth of a newborn and the return to maternal prepregnant physiologic function. Theories surrounding the relatively mysterious biochemical events that prompt intrapartum events abound, though a single explanation for the processes of labor and birth is elusive. The complex signaling between mother, placenta, and fetus that triggers labor initiation and progression is unclear but likely involves interplay between hormonal, mechanical, and immune factors. This chapter presents a detailed discussion of maternal physiologic adaptations in pregnancy as well as labor and birth and the known and postulated mechanisms surrounding the intrapartum events of labor and delivery.

Physiologic adaptive changes in pregnancy

Adaptations of maternal physiology during pregnancy involve the accommodations in multiple systems to support the increasing demands with progressive gestation. Pregnancy adaptations are essential foundations for the unique adjustments required to support the processes of labor and to support the increased demands placed on the maternal-placental-fetal unit during the intrapartum period. Pregnancy can be considered in four separate phases: quiescence, activation, stimulation, and involution [1]. The antepartum period prior to the onset of labor is characterized by quiescence, suppression of uterine activity, reflecting the exquisite balance between the hormonal mileu and responsiveness of the uterus and cervix. Quiescence is mediated by inhibitor hormones, including progesterone, prostacyclin, relaxin, nitric oxide (NO), corticotropin-releasing hormone (CRH), and human placental lactogen (hPL).

Placenta

The placenta, formed by the union of the maternal decidua basalis and the fetal trophoblast, develops in the early days of pregnancy with implantation of the blastocyst. Placental growth continues throughout gestation until term, when the average surface area reaches 12.6 m², increasing to a functional surface area of 90 m² when microvilli surface is considered. Placental weight at term equals approximately 500 g, with dimensions of a diameter of 15–20 cm and thickness of 3 cm [2, p. 3].

The placenta serves as the interface between mother and fetus, supporting perfusion to meet fetal needs in the intrauterine environment. Progressive placental vascular development is stimulated by the hypoxic intrauterine environment characteristic of early pregnancy. Fetal deoxygenated blood passes from the dual umbilical arteries to the placenta. Maternal blood supply is delivered to the placenta by the remodeled spiral arteries, bathing the spaces between chorionic villi (intervillous) with arterial blood at approximately 8–9 weeks of gestation [3]. The chorionic villi contain fetal blood vessels, tightly packed with extensive branching. Maternal-fetal circulatory separation is achieved by several layers of tissue known as the placental barrier or membrane, providing structural separation ­between fetal vessels within the chorionic villi and maternal blood. Chorionic villi represent the anatomic structure across which essential substrates including gases, nutrients, drugs, and wastes must be transported bidirectionally between the maternal and fetal circulations. Transport processes include simple diffusion as the primary mechanism, followed by facilitated diffusion and active transport of select nutritionally essential molecules. Efficiency of placental transport is influenced by placental area, ­diffusing distance, permeability of placental barrier and maternal-fetal blood flow in the intervillous spaces. Additionally, the characteristics of the transported substance that influence transport include concentration and electrical potential gradients, molecule size, binding affinity of substance to carrier protein (e.g., hemoglobin), and solubility (e.g., water, lipid). Factors impacting fetal blood flow include fetal heart activity, influenced by fetal blood pressure, right to left shunts, and vascular resistance, both pulmonary and systemic. Maternal blood flow is determined by perfusion to the uterine and spiral (uteroplacental) arteries, influenced by cardiac output, systemic, peripheral, and uteroplacental resistance.

Endocrine adaptations

Placental endocrine functions are central to the establishment and maintenance of pregnancy. Optimal placental endocrine function requires the involvement of the maternal-placental-fetal unit, reflecting the adaptive transition from independent maternal production [4]. The array of endocrine substances produced by the placenta includes, but is not limited to, polypeptide hormones adrenocorticotropic hormone (ACTH), human chorionic gonadotropin hormone (hCG) and hPL, steroid hormones estrogen and progesterone, neurohormones oxytocin and releasing hormones (gonadotropin, thyroid, growth, corticotropin), growth factors (placental, PlGF; transforming, TGF; insulin-like, IGF), and cytokines (interleukins, IL; tumor necrosis factor, TNF). The placenta assumes neuroendocrine functions during pregnancy, typically regulated by the hypothalamus-pituitary-end organ feedback mechanisms in the nonpregnant state [4].

Progesterone is often referred to as the hormone of pregnancy, reflecting the dominance of this steroid hormone during gestation. The quiescent phase of pregnancy is largely attributed to the inhibitory effects of progesterone. Progesterone inhibits formation of estrogen receptor alpha (ER-α), limiting estrogen sensitivity [5]. The effects of estrogen are opposed by progesterone, resulting in inhibition of gap junction formation and uterine activity. A progesterone-induced increase in NO synthase activity, decreased prostaglandin (PG) production, and reduced development of oxytocin receptors and calcium ion channels combine to enhance uterine quiescence. Cervical integrity is also promoted by progesterone through the inhibition of collagen breakdown.

The ovarian corpus luteum is the primary source of progesterone in early pregnancy, transitioning to primary production from acetate and cholesterol by the placenta with advancing gestation. Progesterone binds to two primary receptor isoforms: progesterone receptor (PR)-A and PR-B. Binding of progesterone to PR-B enhances progesterone function compared to progesterone binding to the truncated PR-A, which antagonizes the effects of progesterone–PR-B binding [6]. During pregnancy, the progesterone binding to PR-B exceeds that of PR-A, promoting the characteristic effects of progesterone. During labor, the PR-A to PR-B ratio changes, promoting the dominant proinflammatory effects of progesterone–PR-A binding [7].

During pregnancy, the delicate balance between estrogen and progesterone is critical to suppression of uterine activity. Progesterone dominance over estrogen during the ­quiescent period of pregnancy overcomes the influence of estrogen-associated effects prior to labor initiation. The placenta is a major source of estriol, the major circulating estrogen in pregnancy. Placental production of estriol is primarily dependent on fetal adrenal production of dehydroepiandrosterone sulfate (DHEAS), hydroxylation of DHEAS by the liver, and aromatization by the placenta [8]. Placenta estriol leads to an increase in the release of maternal prostaglandins, prostaglandin receptors, and oxytocin receptors. An increase in gap junctions, necessary for the rapid transmission of contractile signals, is also due to the influence of estrogen [9]. During the last few weeks of pregnancy, cervical ripening is enhanced by estrogens, promoted by remodeling of collagen and elastin that soften the cervix. Estrogen binding to the ER-α promotes cellular ­signaling with outcomes associated with the actions of estrogen.

Oxytocin is a peptide hormone that has a important role in the labor process. Its relatively short half-life of 3–4 minutes is reduced further when exogenous high doses of oxytocin are infused [10]. Synthesized in the hypothalamus, oxytocin is released from the posterior pituitary and binds to oxytocin receptors for the primary action of uterine ­contraction stimulation.

Uterine adaptation

The adaptations of the uterus accommodate the increasing intrauterine contents as gestation advances. Enlargement of the uterus is due to progressive elasticity and proliferation of smooth muscle contractile units, the myocytes [11]. Early uterine growth is due to myocyte hyperplasia, increase in cell number. Progressive growth with continued gestation is the result of the combined effect of both hyperplasia and hypertrophy, enlargement of existing cells, increasing uterine capacity from 10 ml to 5000 ml at term. The longitudinal and circular muscles of the uterus gain equilibrium in contractile ability by term. Contractile ability is influenced by electrical events in myocyte cellular membranes leading to action potential, the propagation of the action potential to nearby cells via gap junctions, and intracellular calcium availability. The organization of uterine smooth muscle cells promotes a great deal of force along a short distance at low velocity [12].

The coordinated, synchronous contraction of myometrial cells in the contractile fundus is the hallmark of labor onset and progression. Of critical importance is the regulation of uterine contractile function during gestation, delayed until the onset of parturition. The quiescent period prior to labor initiation is characterized by uterine relaxation, with intermittent dyssynchronous uterine activity [8]. The suppression of uterine contractile activity is the combined effect of inhibitors of myometrial activity, which include progesterone, prostacyclin (PG I2), relaxin, NO, and CRH.

Cervical remodeling

During pregnancy, the cervix changes from a firm, rigid structure to one that is pliable and distensible. The cervix is primarily comprised of collagen-producing fibroblasts and smooth muscle cells comprised of cross-linked collagen fibers, elastin, and proteoglycans (glycoaminoglycans attached to a protein). As pregnancy advances, water concentration increases relative to collagen as a result of an increase in highly hydrophilic glycoaminoglycans such as chondroitin sulfate and hyaluronan. The tight collagen bundles relax as a result of remodeling of collagen linkages, maximized by collagen degradation during the process of mechanical stretch during labor. Cervical vascular permeability is promoted by the presence of fibroblasts, leukocytes, macrophages, and eosinophil infiltration.

PGs, a group of hormones resulting from metabolism of arachidonic acid, are produced by the placental and fetal amnion/chorion and are involved in the regulation of uterine activity. Inhibitory PGs (PG I2) reduce uterine activity while stimulatory PGs (PG F2α and E2) promote myometrial contraction [8]. PG production is increased under the influence of estrogens, CRH, and inflammatory cytokines and decreased by progesterone.

CRH is a hypothalamic-releasing hormone regulating ACTH and adrenal cortisol via a negative feedback loop. Beginning in the second trimester, the major source of CRH production transitions from the hypothalamus to the placenta along with a change from negative to positive feedback, with cortisol serving to increase placental CRH production [8]. Stimulants of placental CRH production include PGs, inflammatory cytokines, and neuropeptides. Progesterone and NO inhibit CRH production [11]. The shift to estrogen dominance may be influenced by CRH through stimulation of fetal adrenal activity, promoting release of DHEAS, the precursor of estriol [8]. CRH increases dilation of uterine, fetal, and placental blood vessels and promotes uterine contraction, possibly through the effect on increased fetal membrane production of stimulatory PGs F2α and E2.

Hematologic and cardiac adaptations

Hematologic and cardiac adaptations in pregnancy are essential to promote fetal tolerance for the challenges during labor and blood loss in the third stage of labor. Cardiac output, oxygen consumption, and left ventricular stroke volume are increased with progressive increases in blood volume [13]. Increased maternal blood volume of approximately 40%, composed primarily of increased plasma component due to retention of sodium and body water, peaks in the early third trimester. Red blood cells (RBCs) increase approximately 33%, maximizing oxygen-carrying capacity and provision of oxygen to the fetus. Increased RBC production is promoted by hormone stimulated release of erythropoietin but occurs more slowly than plasma volume adaptations. Plasma proteins are reduced by approximately 10–14%, with implications for drug binding, calcium binding, and metabolism of anesthetic agents during the intrapartum period. Increased production of coagulation factors contributes to a hypercoagulable state, characterized by increased clot formation and inhibition of clot breakdown. Thrombin, the clotting cascade enzyme responsible for the irreversible conversion of soluble fibrinogen to an insoluble fibrin clot, is increased during pregnancy. Thrombin also potentiates clotting through activation of clotting factors V, VII, XI, and XII. During labor and delivery, further increases in factor V and VII provide protection against hemorrhage after placental separation. Fibrinolytic activity is reduced during labor due primarily to plasminogen-activating inhibitor and fibrin-degradation products that peak at placental separation.

The hypertrophy of the maternal vascular system, promoted by NO-mediated vasodilation and progesterone-mediated reduction in vascular tone and resistance, accommodates the increased blood volume and perfusion requirements of the maternal-placental-fetal unit. Increased plasma volume is accompanied by decreased viscosity, reducing resistance to flow. The decreased resistance in the uteroplacental circulation is in part the result of a physiologic arteriovenous shunt that promotes accommodation of increased blood volume