OBG Management

CASE 1 Defining anatomic structures to assure surgical precision

A 44-year-old woman is scheduled for a vaginal hysterectomy and bilateral salpingectomy for abnormal uterine bleeding. In your academic practice, a resident routinely operates with you and is accompanied by a medical student. As this is your first case with each learner, you review the steps of the procedure along with pertinent anatomy. During this discussion, numerous anatomic terms are used to describe anterior cul-de-sac entry, including pubocervical fascia, vesicouterine fold, and vesicovaginal space. Which of these terms, if any, are correct? Is there a preferred term that should be used to teach future learners so we can all “speak” the same language?

What’s in a name?

ObGyns must thoroughly understand pelvic anatomy, since much of our patient care relates to structures in that region. We also must understand the terminology that most appropriately describes each pelvic structure so that we can communicate effectively with colleagues and other providers. The case described above lists several terms that are commonly found in gynecologic textbooks and surgical atlases to describe dissection for vaginal hysterectomy. Lack of a standardized vocabulary, however, often confuses teachers and learners alike, and it highlights the importance of having a universal language to ensure the safe, effective performance of surgical procedures.¹

At first glance, it may seem that anatomic terms are inherently descriptive of the structure they represent; for example, the terms uterus and vagina seem rather obvious. However, many anatomic terms convey ambiguity. Which muscles, for example, constitute the levator ani: pubococcygeus, pubovisceral, pubovisceralis, puboperinealis, puboanalis, pubovaginalis, puborectalis, puborectal, iliococcygeus, ischiococcygeus? Do any of these terms redundantly describe the same structure, or does each term refer to an independent structure?

Standard terminology is essential

Anatomists long have recognized the need for standardized terminology to facilitate clear communication. To provide historical background, the term anatomy is derived from the Greek word for “dissection” or “to cut open.”² Records on the scientific study of human anatomy date back thousands of years.

A brief review of current standardized terminology can be traced back to 1895, with the publication of Basle Terminologia Anatomica.³ That work was intended to provide a consolidated reference with clear direction regarding which anatomic terms should be used. It was updated several times during the ensuing century and was later published as Nomina Anatomica.

In 1990, an international committee was formed with representatives from many anatomical organizations, again with the intention of providing standardized anatomic terminology. Those efforts resulted in the publication of Terminologia Anatomica: International Anatomical Terminology, commonly referred to as TA, in 1998. TA continues to be the referent standard for human anatomic terminology; it was most recently updated in 2011.⁴

CASE 2 Conveying details of mesh erosion

A 52-year-old woman presents to the general gynecology clinic with a 10-year history of pelvic pain and dyspareunia after undergoing vaginal mesh surgery for prolapse and urinary incontinence. On examination, there is a visible ridge of mesh extending from the left side of the midurethra along the anterior and lateral vagina for a length of 1.5 cm. There also is a palpable tight band on the right vaginal wall near the ischial spine that reproduces her pain and causes spasm of the levator ani. You believe the patient needs a urogynecology referral for complications of vaginal mesh. How do you best describe your findings to your urogynecology colleague?

Continue to: Pelvic anatomy from the SGS perspective...

Pelvic anatomy from the SGS perspective

The Society of Gynecologic Surgeons (SGS) recognized the importance of standardizing terminology specific to the pelvis. The SGS Pelvic Anatomy Group thus was organized in 2016. The Pelvic Anatomy Group’s purpose is to help educate physicians about pelvic anatomy, with the overarching goal of compiling instructional materials, primarily from dissections (surgical or cadaveric), and radiologic imaging for all pelvic structures. Throughout the discussions on this initiative, it became clear that standardized terms needed to be established and used for pelvic structures.

While TA is an excellent reference work, it does not include all of the clinically relevant structures for gynecologic surgeons. As physicians, surgeons, and women’s health care providers, we read about and discuss pelvic anatomy structures in medical textbooks, medical literature, and clinical settings that are not necessarily included in TA. In addition, advances in information technology have facilitated the creation of clinically oriented computer-based anatomy programs and expanded the number and availability of electronic publications on surgical and clinical anatomy.⁵ As a result, there is a need not only to standardize nomenclature but also to continually revise and update terminology and integrate new terms, both from an anatomic and a clinical perspective.

The Pelvic Anatomy Group developed a novel approach to anatomic terminology. We decided to review the medical literature, identify the terms used, adjudicate the terms with current TA terms, and provide consensus for the terms and structures in the pelvis. Because of the volume of literature available and the existing number of terms, we divided the pelvis into 4 regions—anterior, apical, posterior, and vulvar—to improve the feasibility of reviewing the medical literature for the entire female pelvis.

Our process for tackling terminology

Our literature review started with the anterior compartment. (For complete details, see our prior publication.³) Modeled on a systematic review, we searched the MEDLINE database for terms related to the anterior pelvis, screened all associated abstracts, and then extracted terms from appropriate papers. We also identified several book chapters from various disciplines (anatomy, gynecology, urology, and radiology) to ensure wide representation of disciplines. We then extracted all terms pertinent to the anterior pelvis.

We organized the terms, with terms that referred to the same anatomic structure grouped together. Whenever possible, we used TA terms as the preferred terms. In this process, however, we identified several clinically relevant terms that were not included in TA: pelvic sidewall, pelvic bones, anterior compartment, pubourethral ligament, vaginal sulcus, and levator hiatus, among others. The new terms were then proposed and agreed on by members of the SGS Pelvic Anatomy Group and accepted by SGS members. We currently are completing a similar process for the apical pelvis, posterior pelvis, and vulvar regions.

TA code numbers pinpoint the nomenclature

As we move forward, we suggest that physicians use TA or other approved terms for patient and research communication. Such use will help standardize anatomic terms and also will improve communication between providers and education for learners.

Continue to: TA includes approved options...

TA includes approved options in English and Latin and lists a unique identification number for each term (shown in parentheses in the examples that follow). For instance, to answer the question posed earlier, the levator ani (A04.5.04.002) is comprised of the pubococcygeus (A04.5.04.003), puborectalis (A04.5.04.007), and iliococcygeus (A04.5.04.008) muscles (FIGURE 1).The terms pubovisceral and pubovisceralis are used synonymously in the literature with pubococcygeus (A04.5.04.003).³ The additional terms puboperinealis (A04.5.04.004), pubovaginalis (A04.5.04.005), and puboanalis (A04.5.04.006) are subcomponents of the pubococcygeus (A04.5.04.003), and this relationship is indicated in TA by indentation formatting.⁴ Finally, the ischiococcygeus (A04.5.04.011) muscle is not considered part of the levator ani (A04.5.04.002).

Revisiting the mesh erosion case: Reporting your findings

After reviewing the recommended terminology for the anterior pelvis,^3,4 you might draft a report as follows: “A mesh erosion was visualized in anterior vaginal wall (A09.1.04.006) at the level of the mid-urethra extending into ‘anterior and lateral vaginal sulci’ (proposed term). In addition, there is a painful tight band in the ‘lateral vaginal wall’ (proposed term) near the ischial spine (A02.5.01.205). Palpation of this band reproduces the patient’s pain and causes secondary spasm of the levator ani (A04.5.04.002).” Certainly, TA identification numbers would not be expected to be included in medical communication; they are included here for reference.

From your description, your urogynecology colleague has a better understanding of the location of your patient’s vaginal mesh and requests her operative report from an outside facility. In the operative report, the surgeon described “placement of mesh into the vagina, dissection through the rectal spaces, and anchoring of the mesh into the levator/pelvic muscles, the cervix, and lastly to the paraurethral ligaments,” and “passage of trocars through the cave of Retzius at the level of the midurethra” (FIGURE 2).

Based on this description, the urogynecologist ascertains that the mesh is located in the anterior vaginal wall (A09.1.04.006), with passage of anchoring arms through the bilateral sacrospinous ligaments (A03.6.03.007) and retropubic space (A10.1.01.003). Exposed mesh is visible, extending from the midurethra to the “anterior and lateral vaginal sulci” (proposed term).

This case clearly demonstrates the importance of communication between providers for patient care, since understanding the patient’s anatomy and the location of the vaginal mesh is important for planning surgical excision of the exposed mesh.

Additional initiatives

Outlining standardized terminology is just the first step toward improving the anatomic “language” used among providers. Ongoing efforts from the SGS Pelvic Anatomy Group include a special imaging group’s review of imaging modalities (ultrasonography, magnetic resonance imaging, computerized tomography) to improve standardization on reporting clinical anatomy. In addition, SGS has developed a group to create educational content related to the structures identified by the terminology group from cadaveric or surgical dissections. Educational materials will be compiled to help physicians and learners expand their anatomic understanding and improve their communication.

Further details of the Pelvic Anatomy Group’s efforts can be found on the SGS website at https://www.sgsonline.org.

CASE 1 Defining anatomic structures to assure surgical precision

A 44-year-old woman is scheduled for a vaginal hysterectomy and bilateral salpingectomy for abnormal uterine bleeding. In your academic practice, a resident routinely operates with you and is accompanied by a medical student. As this is your first case with each learner, you review the steps of the procedure along with pertinent anatomy. During this discussion, numerous anatomic terms are used to describe anterior cul-de-sac entry, including pubocervical fascia, vesicouterine fold, and vesicovaginal space. Which of these terms, if any, are correct? Is there a preferred term that should be used to teach future learners so we can all “speak” the same language?

What’s in a name?

ObGyns must thoroughly understand pelvic anatomy, since much of our patient care relates to structures in that region. We also must understand the terminology that most appropriately describes each pelvic structure so that we can communicate effectively with colleagues and other providers. The case described above lists several terms that are commonly found in gynecologic textbooks and surgical atlases to describe dissection for vaginal hysterectomy. Lack of a standardized vocabulary, however, often confuses teachers and learners alike, and it highlights the importance of having a universal language to ensure the safe, effective performance of surgical procedures.¹

At first glance, it may seem that anatomic terms are inherently descriptive of the structure they represent; for example, the terms uterus and vagina seem rather obvious. However, many anatomic terms convey ambiguity. Which muscles, for example, constitute the levator ani: pubococcygeus, pubovisceral, pubovisceralis, puboperinealis, puboanalis, pubovaginalis, puborectalis, puborectal, iliococcygeus, ischiococcygeus? Do any of these terms redundantly describe the same structure, or does each term refer to an independent structure?

Standard terminology is essential

Anatomists long have recognized the need for standardized terminology to facilitate clear communication. To provide historical background, the term anatomy is derived from the Greek word for “dissection” or “to cut open.”² Records on the scientific study of human anatomy date back thousands of years.

A brief review of current standardized terminology can be traced back to 1895, with the publication of Basle Terminologia Anatomica.³ That work was intended to provide a consolidated reference with clear direction regarding which anatomic terms should be used. It was updated several times during the ensuing century and was later published as Nomina Anatomica.

In 1990, an international committee was formed with representatives from many anatomical organizations, again with the intention of providing standardized anatomic terminology. Those efforts resulted in the publication of Terminologia Anatomica: International Anatomical Terminology, commonly referred to as TA, in 1998. TA continues to be the referent standard for human anatomic terminology; it was most recently updated in 2011.⁴

CASE 2 Conveying details of mesh erosion

A 52-year-old woman presents to the general gynecology clinic with a 10-year history of pelvic pain and dyspareunia after undergoing vaginal mesh surgery for prolapse and urinary incontinence. On examination, there is a visible ridge of mesh extending from the left side of the midurethra along the anterior and lateral vagina for a length of 1.5 cm. There also is a palpable tight band on the right vaginal wall near the ischial spine that reproduces her pain and causes spasm of the levator ani. You believe the patient needs a urogynecology referral for complications of vaginal mesh. How do you best describe your findings to your urogynecology colleague?

Continue to: Pelvic anatomy from the SGS perspective...

Pelvic anatomy from the SGS perspective

The Society of Gynecologic Surgeons (SGS) recognized the importance of standardizing terminology specific to the pelvis. The SGS Pelvic Anatomy Group thus was organized in 2016. The Pelvic Anatomy Group’s purpose is to help educate physicians about pelvic anatomy, with the overarching goal of compiling instructional materials, primarily from dissections (surgical or cadaveric), and radiologic imaging for all pelvic structures. Throughout the discussions on this initiative, it became clear that standardized terms needed to be established and used for pelvic structures.

While TA is an excellent reference work, it does not include all of the clinically relevant structures for gynecologic surgeons. As physicians, surgeons, and women’s health care providers, we read about and discuss pelvic anatomy structures in medical textbooks, medical literature, and clinical settings that are not necessarily included in TA. In addition, advances in information technology have facilitated the creation of clinically oriented computer-based anatomy programs and expanded the number and availability of electronic publications on surgical and clinical anatomy.⁵ As a result, there is a need not only to standardize nomenclature but also to continually revise and update terminology and integrate new terms, both from an anatomic and a clinical perspective.

The Pelvic Anatomy Group developed a novel approach to anatomic terminology. We decided to review the medical literature, identify the terms used, adjudicate the terms with current TA terms, and provide consensus for the terms and structures in the pelvis. Because of the volume of literature available and the existing number of terms, we divided the pelvis into 4 regions—anterior, apical, posterior, and vulvar—to improve the feasibility of reviewing the medical literature for the entire female pelvis.

Our process for tackling terminology

Our literature review started with the anterior compartment. (For complete details, see our prior publication.³) Modeled on a systematic review, we searched the MEDLINE database for terms related to the anterior pelvis, screened all associated abstracts, and then extracted terms from appropriate papers. We also identified several book chapters from various disciplines (anatomy, gynecology, urology, and radiology) to ensure wide representation of disciplines. We then extracted all terms pertinent to the anterior pelvis.

We organized the terms, with terms that referred to the same anatomic structure grouped together. Whenever possible, we used TA terms as the preferred terms. In this process, however, we identified several clinically relevant terms that were not included in TA: pelvic sidewall, pelvic bones, anterior compartment, pubourethral ligament, vaginal sulcus, and levator hiatus, among others. The new terms were then proposed and agreed on by members of the SGS Pelvic Anatomy Group and accepted by SGS members. We currently are completing a similar process for the apical pelvis, posterior pelvis, and vulvar regions.

TA code numbers pinpoint the nomenclature

As we move forward, we suggest that physicians use TA or other approved terms for patient and research communication. Such use will help standardize anatomic terms and also will improve communication between providers and education for learners.

Continue to: TA includes approved options...

TA includes approved options in English and Latin and lists a unique identification number for each term (shown in parentheses in the examples that follow). For instance, to answer the question posed earlier, the levator ani (A04.5.04.002) is comprised of the pubococcygeus (A04.5.04.003), puborectalis (A04.5.04.007), and iliococcygeus (A04.5.04.008) muscles (FIGURE 1).The terms pubovisceral and pubovisceralis are used synonymously in the literature with pubococcygeus (A04.5.04.003).³ The additional terms puboperinealis (A04.5.04.004), pubovaginalis (A04.5.04.005), and puboanalis (A04.5.04.006) are subcomponents of the pubococcygeus (A04.5.04.003), and this relationship is indicated in TA by indentation formatting.⁴ Finally, the ischiococcygeus (A04.5.04.011) muscle is not considered part of the levator ani (A04.5.04.002).

Revisiting the mesh erosion case: Reporting your findings

After reviewing the recommended terminology for the anterior pelvis,^3,4 you might draft a report as follows: “A mesh erosion was visualized in anterior vaginal wall (A09.1.04.006) at the level of the mid-urethra extending into ‘anterior and lateral vaginal sulci’ (proposed term). In addition, there is a painful tight band in the ‘lateral vaginal wall’ (proposed term) near the ischial spine (A02.5.01.205). Palpation of this band reproduces the patient’s pain and causes secondary spasm of the levator ani (A04.5.04.002).” Certainly, TA identification numbers would not be expected to be included in medical communication; they are included here for reference.

From your description, your urogynecology colleague has a better understanding of the location of your patient’s vaginal mesh and requests her operative report from an outside facility. In the operative report, the surgeon described “placement of mesh into the vagina, dissection through the rectal spaces, and anchoring of the mesh into the levator/pelvic muscles, the cervix, and lastly to the paraurethral ligaments,” and “passage of trocars through the cave of Retzius at the level of the midurethra” (FIGURE 2).

Based on this description, the urogynecologist ascertains that the mesh is located in the anterior vaginal wall (A09.1.04.006), with passage of anchoring arms through the bilateral sacrospinous ligaments (A03.6.03.007) and retropubic space (A10.1.01.003). Exposed mesh is visible, extending from the midurethra to the “anterior and lateral vaginal sulci” (proposed term).

This case clearly demonstrates the importance of communication between providers for patient care, since understanding the patient’s anatomy and the location of the vaginal mesh is important for planning surgical excision of the exposed mesh.

Additional initiatives

Outlining standardized terminology is just the first step toward improving the anatomic “language” used among providers. Ongoing efforts from the SGS Pelvic Anatomy Group include a special imaging group’s review of imaging modalities (ultrasonography, magnetic resonance imaging, computerized tomography) to improve standardization on reporting clinical anatomy. In addition, SGS has developed a group to create educational content related to the structures identified by the terminology group from cadaveric or surgical dissections. Educational materials will be compiled to help physicians and learners expand their anatomic understanding and improve their communication.

Further details of the Pelvic Anatomy Group’s efforts can be found on the SGS website at https://www.sgsonline.org.

CASE 1 Defining anatomic structures to assure surgical precision

A 44-year-old woman is scheduled for a vaginal hysterectomy and bilateral salpingectomy for abnormal uterine bleeding. In your academic practice, a resident routinely operates with you and is accompanied by a medical student. As this is your first case with each learner, you review the steps of the procedure along with pertinent anatomy. During this discussion, numerous anatomic terms are used to describe anterior cul-de-sac entry, including pubocervical fascia, vesicouterine fold, and vesicovaginal space. Which of these terms, if any, are correct? Is there a preferred term that should be used to teach future learners so we can all “speak” the same language?

What’s in a name?

ObGyns must thoroughly understand pelvic anatomy, since much of our patient care relates to structures in that region. We also must understand the terminology that most appropriately describes each pelvic structure so that we can communicate effectively with colleagues and other providers. The case described above lists several terms that are commonly found in gynecologic textbooks and surgical atlases to describe dissection for vaginal hysterectomy. Lack of a standardized vocabulary, however, often confuses teachers and learners alike, and it highlights the importance of having a universal language to ensure the safe, effective performance of surgical procedures.¹

At first glance, it may seem that anatomic terms are inherently descriptive of the structure they represent; for example, the terms uterus and vagina seem rather obvious. However, many anatomic terms convey ambiguity. Which muscles, for example, constitute the levator ani: pubococcygeus, pubovisceral, pubovisceralis, puboperinealis, puboanalis, pubovaginalis, puborectalis, puborectal, iliococcygeus, ischiococcygeus? Do any of these terms redundantly describe the same structure, or does each term refer to an independent structure?

Standard terminology is essential

Anatomists long have recognized the need for standardized terminology to facilitate clear communication. To provide historical background, the term anatomy is derived from the Greek word for “dissection” or “to cut open.”² Records on the scientific study of human anatomy date back thousands of years.

A brief review of current standardized terminology can be traced back to 1895, with the publication of Basle Terminologia Anatomica.³ That work was intended to provide a consolidated reference with clear direction regarding which anatomic terms should be used. It was updated several times during the ensuing century and was later published as Nomina Anatomica.

In 1990, an international committee was formed with representatives from many anatomical organizations, again with the intention of providing standardized anatomic terminology. Those efforts resulted in the publication of Terminologia Anatomica: International Anatomical Terminology, commonly referred to as TA, in 1998. TA continues to be the referent standard for human anatomic terminology; it was most recently updated in 2011.⁴

CASE 2 Conveying details of mesh erosion

A 52-year-old woman presents to the general gynecology clinic with a 10-year history of pelvic pain and dyspareunia after undergoing vaginal mesh surgery for prolapse and urinary incontinence. On examination, there is a visible ridge of mesh extending from the left side of the midurethra along the anterior and lateral vagina for a length of 1.5 cm. There also is a palpable tight band on the right vaginal wall near the ischial spine that reproduces her pain and causes spasm of the levator ani. You believe the patient needs a urogynecology referral for complications of vaginal mesh. How do you best describe your findings to your urogynecology colleague?

Continue to: Pelvic anatomy from the SGS perspective...

Pelvic anatomy from the SGS perspective

The Society of Gynecologic Surgeons (SGS) recognized the importance of standardizing terminology specific to the pelvis. The SGS Pelvic Anatomy Group thus was organized in 2016. The Pelvic Anatomy Group’s purpose is to help educate physicians about pelvic anatomy, with the overarching goal of compiling instructional materials, primarily from dissections (surgical or cadaveric), and radiologic imaging for all pelvic structures. Throughout the discussions on this initiative, it became clear that standardized terms needed to be established and used for pelvic structures.

While TA is an excellent reference work, it does not include all of the clinically relevant structures for gynecologic surgeons. As physicians, surgeons, and women’s health care providers, we read about and discuss pelvic anatomy structures in medical textbooks, medical literature, and clinical settings that are not necessarily included in TA. In addition, advances in information technology have facilitated the creation of clinically oriented computer-based anatomy programs and expanded the number and availability of electronic publications on surgical and clinical anatomy.⁵ As a result, there is a need not only to standardize nomenclature but also to continually revise and update terminology and integrate new terms, both from an anatomic and a clinical perspective.

The Pelvic Anatomy Group developed a novel approach to anatomic terminology. We decided to review the medical literature, identify the terms used, adjudicate the terms with current TA terms, and provide consensus for the terms and structures in the pelvis. Because of the volume of literature available and the existing number of terms, we divided the pelvis into 4 regions—anterior, apical, posterior, and vulvar—to improve the feasibility of reviewing the medical literature for the entire female pelvis.

Our process for tackling terminology

Our literature review started with the anterior compartment. (For complete details, see our prior publication.³) Modeled on a systematic review, we searched the MEDLINE database for terms related to the anterior pelvis, screened all associated abstracts, and then extracted terms from appropriate papers. We also identified several book chapters from various disciplines (anatomy, gynecology, urology, and radiology) to ensure wide representation of disciplines. We then extracted all terms pertinent to the anterior pelvis.

We organized the terms, with terms that referred to the same anatomic structure grouped together. Whenever possible, we used TA terms as the preferred terms. In this process, however, we identified several clinically relevant terms that were not included in TA: pelvic sidewall, pelvic bones, anterior compartment, pubourethral ligament, vaginal sulcus, and levator hiatus, among others. The new terms were then proposed and agreed on by members of the SGS Pelvic Anatomy Group and accepted by SGS members. We currently are completing a similar process for the apical pelvis, posterior pelvis, and vulvar regions.

TA code numbers pinpoint the nomenclature

As we move forward, we suggest that physicians use TA or other approved terms for patient and research communication. Such use will help standardize anatomic terms and also will improve communication between providers and education for learners.

Continue to: TA includes approved options...

TA includes approved options in English and Latin and lists a unique identification number for each term (shown in parentheses in the examples that follow). For instance, to answer the question posed earlier, the levator ani (A04.5.04.002) is comprised of the pubococcygeus (A04.5.04.003), puborectalis (A04.5.04.007), and iliococcygeus (A04.5.04.008) muscles (FIGURE 1).The terms pubovisceral and pubovisceralis are used synonymously in the literature with pubococcygeus (A04.5.04.003).³ The additional terms puboperinealis (A04.5.04.004), pubovaginalis (A04.5.04.005), and puboanalis (A04.5.04.006) are subcomponents of the pubococcygeus (A04.5.04.003), and this relationship is indicated in TA by indentation formatting.⁴ Finally, the ischiococcygeus (A04.5.04.011) muscle is not considered part of the levator ani (A04.5.04.002).

Revisiting the mesh erosion case: Reporting your findings

After reviewing the recommended terminology for the anterior pelvis,^3,4 you might draft a report as follows: “A mesh erosion was visualized in anterior vaginal wall (A09.1.04.006) at the level of the mid-urethra extending into ‘anterior and lateral vaginal sulci’ (proposed term). In addition, there is a painful tight band in the ‘lateral vaginal wall’ (proposed term) near the ischial spine (A02.5.01.205). Palpation of this band reproduces the patient’s pain and causes secondary spasm of the levator ani (A04.5.04.002).” Certainly, TA identification numbers would not be expected to be included in medical communication; they are included here for reference.

From your description, your urogynecology colleague has a better understanding of the location of your patient’s vaginal mesh and requests her operative report from an outside facility. In the operative report, the surgeon described “placement of mesh into the vagina, dissection through the rectal spaces, and anchoring of the mesh into the levator/pelvic muscles, the cervix, and lastly to the paraurethral ligaments,” and “passage of trocars through the cave of Retzius at the level of the midurethra” (FIGURE 2).

Based on this description, the urogynecologist ascertains that the mesh is located in the anterior vaginal wall (A09.1.04.006), with passage of anchoring arms through the bilateral sacrospinous ligaments (A03.6.03.007) and retropubic space (A10.1.01.003). Exposed mesh is visible, extending from the midurethra to the “anterior and lateral vaginal sulci” (proposed term).

This case clearly demonstrates the importance of communication between providers for patient care, since understanding the patient’s anatomy and the location of the vaginal mesh is important for planning surgical excision of the exposed mesh.

Additional initiatives

Outlining standardized terminology is just the first step toward improving the anatomic “language” used among providers. Ongoing efforts from the SGS Pelvic Anatomy Group include a special imaging group’s review of imaging modalities (ultrasonography, magnetic resonance imaging, computerized tomography) to improve standardization on reporting clinical anatomy. In addition, SGS has developed a group to create educational content related to the structures identified by the terminology group from cadaveric or surgical dissections. Educational materials will be compiled to help physicians and learners expand their anatomic understanding and improve their communication.

Further details of the Pelvic Anatomy Group’s efforts can be found on the SGS website at https://www.sgsonline.org.

As the face of health care changes and physicians are presented with new challenges, we need to keep focused on our priorities: maintain outstanding patient care, continue to grow ourselves as physicians, and train the next generation of women’s health care providers. The theme of the SGS 2019 annual scientific meeting in Tucson, Arizona, “Looking Forward: Achieving Excellence in Gynecologic Surgery for Ourselves, Our Learners, and Our Patients,” focused on these very concepts. This 2-part special section of OBG Management highlights some of the meeting’s outstanding presentations.

The excellent postgraduate workshops included courses on simulation of laparoscopic suturing, surgical strategies for fibroid management, and a quality improvement boot camp. In addition, Rebecca Rogers, MD, Cassandra Carberry, MD, and Danielle Antosh, MD, along with physical therapist Uchenna Ossai, PT, DPT, WCS, ran a course on pelvic surgery and its impact on sexual function, tackling an important, often difficult topic for gynecologic surgeons. In part 2 of this special section, these authors highlight current knowledge on sexual function related to surgery and offer an initial evaluation and treatment approach for women with sexual dysfunction after surgery.

Peter Jeppson, MD, Audra Jolyn Hill, MD, and Sunil Balgobin, MD, have been integral leaders of the SGS Pelvic Anatomy Group, which has a mission to educate physicians about pelvic anatomy. Early discussions made it clear that standardized terms needed to be established and used for pelvic structures. In this special section, these authors illustrate the importance of standard terminology to optimize patient care, and they review pertinent vaginal compartment structures for the gynecologist.

Along with outstanding plenary talks focusing on surgical education research by Gary Dunnington, MD, and health disparities in gynecologic surgery by Marcela del Carmen, MD, MPH, 2 special focus speakers were featured. Sean Dowdy, MD, highlighted advances in the perioperative care of gynecologic surgery patients. In this special section, he reviews best practices for enhanced recovery after surgery (ERAS) and describes his experience with implementing a successful ERAS program.

Cheryl Iglesia, MD, covered energy-based therapies in female genital cosmetic surgery. In part 2 of this special section, she highlights, with Sarah Ward, MD, the salient points from her presentation, including the mechanism of action of laser therapy on tissue remodeling as well as some therapeutic uses for and outcomes of laser therapy in gynecologic care.

I hope you enjoy the content of this special section (part 2 will follow in the May issue) and find that it helps you achieve excellence in gynecologic surgery for yourself, your learners, and your patients!

As the face of health care changes and physicians are presented with new challenges, we need to keep focused on our priorities: maintain outstanding patient care, continue to grow ourselves as physicians, and train the next generation of women’s health care providers. The theme of the SGS 2019 annual scientific meeting in Tucson, Arizona, “Looking Forward: Achieving Excellence in Gynecologic Surgery for Ourselves, Our Learners, and Our Patients,” focused on these very concepts. This 2-part special section of OBG Management highlights some of the meeting’s outstanding presentations.

The excellent postgraduate workshops included courses on simulation of laparoscopic suturing, surgical strategies for fibroid management, and a quality improvement boot camp. In addition, Rebecca Rogers, MD, Cassandra Carberry, MD, and Danielle Antosh, MD, along with physical therapist Uchenna Ossai, PT, DPT, WCS, ran a course on pelvic surgery and its impact on sexual function, tackling an important, often difficult topic for gynecologic surgeons. In part 2 of this special section, these authors highlight current knowledge on sexual function related to surgery and offer an initial evaluation and treatment approach for women with sexual dysfunction after surgery.

Peter Jeppson, MD, Audra Jolyn Hill, MD, and Sunil Balgobin, MD, have been integral leaders of the SGS Pelvic Anatomy Group, which has a mission to educate physicians about pelvic anatomy. Early discussions made it clear that standardized terms needed to be established and used for pelvic structures. In this special section, these authors illustrate the importance of standard terminology to optimize patient care, and they review pertinent vaginal compartment structures for the gynecologist.

Along with outstanding plenary talks focusing on surgical education research by Gary Dunnington, MD, and health disparities in gynecologic surgery by Marcela del Carmen, MD, MPH, 2 special focus speakers were featured. Sean Dowdy, MD, highlighted advances in the perioperative care of gynecologic surgery patients. In this special section, he reviews best practices for enhanced recovery after surgery (ERAS) and describes his experience with implementing a successful ERAS program.

Cheryl Iglesia, MD, covered energy-based therapies in female genital cosmetic surgery. In part 2 of this special section, she highlights, with Sarah Ward, MD, the salient points from her presentation, including the mechanism of action of laser therapy on tissue remodeling as well as some therapeutic uses for and outcomes of laser therapy in gynecologic care.

I hope you enjoy the content of this special section (part 2 will follow in the May issue) and find that it helps you achieve excellence in gynecologic surgery for yourself, your learners, and your patients!

As the face of health care changes and physicians are presented with new challenges, we need to keep focused on our priorities: maintain outstanding patient care, continue to grow ourselves as physicians, and train the next generation of women’s health care providers. The theme of the SGS 2019 annual scientific meeting in Tucson, Arizona, “Looking Forward: Achieving Excellence in Gynecologic Surgery for Ourselves, Our Learners, and Our Patients,” focused on these very concepts. This 2-part special section of OBG Management highlights some of the meeting’s outstanding presentations.

The excellent postgraduate workshops included courses on simulation of laparoscopic suturing, surgical strategies for fibroid management, and a quality improvement boot camp. In addition, Rebecca Rogers, MD, Cassandra Carberry, MD, and Danielle Antosh, MD, along with physical therapist Uchenna Ossai, PT, DPT, WCS, ran a course on pelvic surgery and its impact on sexual function, tackling an important, often difficult topic for gynecologic surgeons. In part 2 of this special section, these authors highlight current knowledge on sexual function related to surgery and offer an initial evaluation and treatment approach for women with sexual dysfunction after surgery.

Peter Jeppson, MD, Audra Jolyn Hill, MD, and Sunil Balgobin, MD, have been integral leaders of the SGS Pelvic Anatomy Group, which has a mission to educate physicians about pelvic anatomy. Early discussions made it clear that standardized terms needed to be established and used for pelvic structures. In this special section, these authors illustrate the importance of standard terminology to optimize patient care, and they review pertinent vaginal compartment structures for the gynecologist.

Along with outstanding plenary talks focusing on surgical education research by Gary Dunnington, MD, and health disparities in gynecologic surgery by Marcela del Carmen, MD, MPH, 2 special focus speakers were featured. Sean Dowdy, MD, highlighted advances in the perioperative care of gynecologic surgery patients. In this special section, he reviews best practices for enhanced recovery after surgery (ERAS) and describes his experience with implementing a successful ERAS program.

Cheryl Iglesia, MD, covered energy-based therapies in female genital cosmetic surgery. In part 2 of this special section, she highlights, with Sarah Ward, MD, the salient points from her presentation, including the mechanism of action of laser therapy on tissue remodeling as well as some therapeutic uses for and outcomes of laser therapy in gynecologic care.

I hope you enjoy the content of this special section (part 2 will follow in the May issue) and find that it helps you achieve excellence in gynecologic surgery for yourself, your learners, and your patients!

Our specialty is focusing now more intently on perioperative optimization, commonly referred to as enhanced recovery after surgery (ERAS), a concept championed first and most visibly by colorectal surgeons in the 1990s.¹ Both academic and nonacademic practices are challenging long-held beliefs about perioperative management.

The 3 tenets of ERAS

In multiple surgical specialties, proper implementation of 3 tenets—early feeding, perioperative euvolemia, and multimodal pain control—reduces the length of hospital stay, improves patient satisfaction, reduces complications, lowers health care costs, and most importantly hastens patient recovery.

1 Early feeding

Just as athletes hydrate and carbohydrate load prior to a competition, patients benefit if fluids and calories are not withheld in anticipation of a physiologically stressful surgical procedure. Similarly, modest benefit is associated with carbohydrate loading as a liquid supplement 2 hours before surgery.² The American Society of Anesthesiologists guidelines state that while solid foods should not be consumed after midnight before surgery, clear liquids safely may be withheld for only 2 hours prior to anesthesia induction, and systematic reviews have failed to show harm.^3,4 All patients, including those undergoing colonic resections, are allowed to eat a general diet as tolerated the evening before surgery, supplemented with caloric-dense nutritional supplements.

2 Multimodal pain control

Postsurgical pain is a top patient concern. Pain control is critical for rapid recovery; it helps avoid upregulation of the sympathetic axis and permits ambulation and resumption of normal activities. Although opioids relieve pain, they should not be considered a primary pain control approach.

Responding to the opioid epidemic, in 2015 the Centers for Disease Control and Prevention identified opioid overdose prevention as one of the top 5 public health challenges; notably, approximately 6% of patients will experience new, persistent opioid use following surgery.⁵ Optimal pain management therefore should provide effective pain relief while minimizing opioid use.

Preemptive oral acetaminophen, gabapentin, and celecoxib should be used routinely prior to incision; nonsteroidal anti-inflammatory drugs should be scheduled postoperatively. Even after a complex cytoreductive laparotomy, pain may be controlled with oral rather than intravenous (IV) medications in most patients, with opioid requirements averaging just 2 to 4 tablets of oxycodone in the first 48 hours after surgery, in our experience. The most critical need for pain medications occurs in the first 48 hours after surgery, which highlights the importance of local or regional analgesia. In one investigation, implementation of multimodal pain management that included incisional injection of liposomal bupivacaine reduced patient-controlled analgesia use to less than 5% after laparotomy.⁶ The need for opioids more than a week postoperatively is uncommon even after a laparotomy.

3 Perioperative euvolemia

Maintaining euvolemia is a central and underrecognized tenet of enhanced recovery pathways, and it facilitates the other 2 tenets of early feeding and optimal pain control. Overhydrated patients have more pain and prolonged recovery of bowel function. Unfortunately, euvolemia is the most difficult ERAS component to implement, requiring seamless communication between all members of the surgical team.

Continue to: Fluid therapy...

Fluid therapy should be respected as a pharmacologic agent with both benefits and risks. Recognizing that a single liter of lactated Ringer’s solution contains the sodium load of more than 30 bags of potato chips (and normal saline contains far more), one can imagine the impact of 10 L of solution on peripheral and bowel edema and on overall recovery. Importantly, euvolemia must be initiated during surgery. A meta-analysis of nearly 1,000 randomly assigned patients showed that benefits were limited when euvolemia was initiated in the postoperative period.⁷

When it comes to maintaining euvolemia, particular care must be taken to avoid erring toward hyperadherence. No difference in hospital length of stay, complications, or ileus was observed when patients were randomly assigned to goal-directed fluid therapy or standard practice.⁸ However, differences in the volume of fluid administered were relatively small, and while there was evidence of underhydration (likely responsible for acute kidney injury), there was no evidence of overhydration. For example, 4 L of fluid is likely superior to 15 L, but it may not be clinically different from 4.5 L. A threshold of fluid restriction is likely to be reached; that is, additional benefit is not achieved and, instead, detrimental effects may occur.

Rather than a specific directive, a more clinically relevant goal may be to replace insensible fluid losses and to maintain perfusion and blood pressure with the lowest volume possible. Note that estimation of fluid requirements is vastly simplified by omitting mechanical bowel preparation. Postoperatively, permissive oliguria (20 mL/h) is allowed since reduced urine output is a normal response to surgery (as a result of inappropriate secretion of antidiuretic hormone) and does not necessitate administration of a fluid bolus. Above all, anesthesiologists should acknowledge that fluid administration’s effects on a patient extend past the postanesthesia care unit, and the entire surgical team should be invested in the patient’s long-term recovery.

Our experience with ERAS

In 2011, Mayo Clinic was the first institution to implement enhanced recovery on a large scale in gynecologic surgery. We have subsequently made multiple pathway modifications in the spirit of continuous improvement (FIGURE 1).

For patients with ovarian cancer requiring extended procedures for cytoreduction via laparotomy (such as colon resection, splenectomy, diaphragm resection), enhanced recovery reduced the median hospital stay by 3 days, patient-controlled IV analgesia use by 88%, and postoperative opioid requirements by 90%.^9,10

At 48 hours after surgery, 40% of our patients require no opioids or tramadol, and epidurals are not utilized because of their effects on ambulation and the potential for hypotension. These reductions were met with stable to improved pain scores, a 60% decrease in nausea, and a 50% reduction in adynamic ileus.^9,10

Our initial efforts reduced 30-day costs of care by more than $850,000 in just 6 months, with savings of more than $7,600 for each patient undergoing a complex cytoreduction. Furthermore, these improvements allowed consolidation of our inpatient unit with those of other surgical specialties, serving higher volumes of patients within a smaller inpatient footprint. This contraction of inpatient services has accounted for an additional $1.1 million in savings every year since implementation (FIGURE 2).^9,10

Our group is not alone in realizing these benefits, and interest has intensified as demonstrated by the fact that the ERAS Society guidelines are among the all-time most downloaded articles in Gynecologic Oncology.^11,12 Although our research to demonstrate safety has focused on women undergoing complex oncologic operations, ERAS nevertheless hastens recovery, improves patient satisfaction, and adds value for all patients undergoing gynecologic surgery.

Continue to: Collateral improvements to practice...

Collateral improvements to practice

Clinical optimization using evidence-based practices such as enhanced recovery pathways can result in immediate patient benefit. Affecting such profound clinical improvements is energizing and creates a unique opportunity to transform the culture of the entire health care team. Irrespective of our provider roles (surgeon, anesthesiologist, nurse) or areas of interest (practice, research, education, leadership), we are united by a common purpose: to improve the human condition.¹³ Reaffirming this common purpose, through the collective effort involved in establishing a standardized enhanced recovery pathway, has allowed our practice and those of others to move beyond enhanced recovery and improve other areas of practice.

Other positive effects. The long-term collateral impact of this culture change at our institution is arguably more important than enhanced recovery itself. Examples of downstream impact include^14,15:

• 80% reduction in surgical site infection
• 50% reduction in anastomotic leaks
• 60% reduction in blood utilization for patients undergoing surgery for ovarian cancer.

Team-based pragmatic strategies. Additionally, our willingness to make decisions as a division rather than as individuals facilitated universal implementation of sentinel lymph node biopsy for patients with endometrial cancer and standardized imaging, testing, and surgical decision making for patients with ovarian and endometrial cancer.

The interventions associated with these improvements were not tested in a randomized fashion; however, rather than await perfect data, we made informed decisions based on imperfect data together with a commitment to continuous data review. We find this to be an effective strategy if our goal is to ensure that tomorrow’s outcomes will be better than yesterday’s. In this way, pragmatic trials can be extremely effective in rural settings and tertiary centers.

Barriers to innovation

The widely reported benefits of enhanced recovery beg the question, Why has enhanced recovery not been adopted universally as standard of care? The answer is multifaceted and highlights long-standing shortcomings in our health care system.

Most importantly, our health care system lacks a robust interface to link discovery of new techniques, treatments, and workflows to clinical practice. Perhaps the best example of this is the adoption of minimally invasive surgery (MIS) for endometrial cancer. Ten years have passed since randomized trials showed MIS has equivalent oncologic outcomes and superior recovery compared to laparotomy, yet in the United States less than 50% of women with endometrial cancer benefit.^16,17

However, even surgeons who are knowledgeable about recent innovations and genuinely wish to promote improvements may face near-insurmountable skepticism. Blind faith in our abilities and outcomes, overprotection of autonomy, close-mindedness, and satisfaction with the status quo are common responses to innovation and are the enemies of change. Resistance often comes from good intentions, but our desire to avoid complications may result in actions that could just as accurately be labeled superstitious as conservative. These observations suggest that developing methods to incorporate evidence-based practice into routine clinical use is the rate-limiting step in improving surgical quality.

Principles essential to change

Various methodologies have been described to manage change and facilitate implementation of new workflows and practices. Irrespective of the method used, including the more formal discipline of implementation science, at least 4 principles must be followed:

1. Teamwork. Mutual trust, mutual respect, and a sense of common purpose are minimum requirements for any successful initiative. Standardization is difficult or impossible without these elements. Thus, establishing a healthy team is the first step in implementing change.

2. Stakeholder analysis. Feedback from surgeons, nurses, residents, fellows, anesthesiologists, pharmacists, nurse anesthetists, and administrators is necessary to obtain diverse perspectives, facilitate engagement, and promote collaborative management. Negativity and resistance are common reactions to change, and it is particularly important to include those who are most skeptical in the stakeholder analysis to mitigate sabotage.

3. Concrete metrics. Success is possible only if defined a priori by specific and achievable goals. Counterbalances also are important to ensure that interventions do not have unintended consequences. Once a goal is met (for example, reduced hospital length of stay or costs), relevant metrics should be monitored after project completion for a minimum of 3 years to avoid regression to the pre-project state.

4. Leadership. The project champion responsible for the initiative must objectively facilitate all of the above and ensure excellent communication between stakeholders to nurture long-term engagement. Despite best efforts, if a minority of the group rejects compromise, this creates an opportunity to compare outcomes between those who do and do not accept the proposed change. Progress realized by early adopters may convince resistors to conform at a later time. Alternatively, the project champion also must have the insight to recognize when a proposed change is impossible at that point in time with that particular group. For example, our own initial attempts to implement enhanced recovery stalled in 2008, but they were successful 3 years later in a different environment.

Continue to: Although a discussion of leadership styles...

Although a discussion of leadership styles is beyond the scope of this article, in our experience, the most successful model is one of servant leadership that is team oriented rather than star dominated. Rather than being led by a single surgeon, each of the 4 quality improvement projects reviewed above (ERAS, and reductions in anastomotic leak, surgical site infection, and blood transfusion) that grew from enhanced recovery included trainees and was led by a different champion, encouraging teamwork and promoting career development. Such a model also supports the Accreditation Council for Graduate Medical Education’s emphasis on quality improvement education.

Our specialty is focusing now more intently on perioperative optimization, commonly referred to as enhanced recovery after surgery (ERAS), a concept championed first and most visibly by colorectal surgeons in the 1990s.¹ Both academic and nonacademic practices are challenging long-held beliefs about perioperative management.

The 3 tenets of ERAS

In multiple surgical specialties, proper implementation of 3 tenets—early feeding, perioperative euvolemia, and multimodal pain control—reduces the length of hospital stay, improves patient satisfaction, reduces complications, lowers health care costs, and most importantly hastens patient recovery.

1 Early feeding

Just as athletes hydrate and carbohydrate load prior to a competition, patients benefit if fluids and calories are not withheld in anticipation of a physiologically stressful surgical procedure. Similarly, modest benefit is associated with carbohydrate loading as a liquid supplement 2 hours before surgery.² The American Society of Anesthesiologists guidelines state that while solid foods should not be consumed after midnight before surgery, clear liquids safely may be withheld for only 2 hours prior to anesthesia induction, and systematic reviews have failed to show harm.^3,4 All patients, including those undergoing colonic resections, are allowed to eat a general diet as tolerated the evening before surgery, supplemented with caloric-dense nutritional supplements.

2 Multimodal pain control

Postsurgical pain is a top patient concern. Pain control is critical for rapid recovery; it helps avoid upregulation of the sympathetic axis and permits ambulation and resumption of normal activities. Although opioids relieve pain, they should not be considered a primary pain control approach.

Responding to the opioid epidemic, in 2015 the Centers for Disease Control and Prevention identified opioid overdose prevention as one of the top 5 public health challenges; notably, approximately 6% of patients will experience new, persistent opioid use following surgery.⁵ Optimal pain management therefore should provide effective pain relief while minimizing opioid use.

Preemptive oral acetaminophen, gabapentin, and celecoxib should be used routinely prior to incision; nonsteroidal anti-inflammatory drugs should be scheduled postoperatively. Even after a complex cytoreductive laparotomy, pain may be controlled with oral rather than intravenous (IV) medications in most patients, with opioid requirements averaging just 2 to 4 tablets of oxycodone in the first 48 hours after surgery, in our experience. The most critical need for pain medications occurs in the first 48 hours after surgery, which highlights the importance of local or regional analgesia. In one investigation, implementation of multimodal pain management that included incisional injection of liposomal bupivacaine reduced patient-controlled analgesia use to less than 5% after laparotomy.⁶ The need for opioids more than a week postoperatively is uncommon even after a laparotomy.

3 Perioperative euvolemia

Maintaining euvolemia is a central and underrecognized tenet of enhanced recovery pathways, and it facilitates the other 2 tenets of early feeding and optimal pain control. Overhydrated patients have more pain and prolonged recovery of bowel function. Unfortunately, euvolemia is the most difficult ERAS component to implement, requiring seamless communication between all members of the surgical team.

Continue to: Fluid therapy...

Fluid therapy should be respected as a pharmacologic agent with both benefits and risks. Recognizing that a single liter of lactated Ringer’s solution contains the sodium load of more than 30 bags of potato chips (and normal saline contains far more), one can imagine the impact of 10 L of solution on peripheral and bowel edema and on overall recovery. Importantly, euvolemia must be initiated during surgery. A meta-analysis of nearly 1,000 randomly assigned patients showed that benefits were limited when euvolemia was initiated in the postoperative period.⁷

When it comes to maintaining euvolemia, particular care must be taken to avoid erring toward hyperadherence. No difference in hospital length of stay, complications, or ileus was observed when patients were randomly assigned to goal-directed fluid therapy or standard practice.⁸ However, differences in the volume of fluid administered were relatively small, and while there was evidence of underhydration (likely responsible for acute kidney injury), there was no evidence of overhydration. For example, 4 L of fluid is likely superior to 15 L, but it may not be clinically different from 4.5 L. A threshold of fluid restriction is likely to be reached; that is, additional benefit is not achieved and, instead, detrimental effects may occur.

Rather than a specific directive, a more clinically relevant goal may be to replace insensible fluid losses and to maintain perfusion and blood pressure with the lowest volume possible. Note that estimation of fluid requirements is vastly simplified by omitting mechanical bowel preparation. Postoperatively, permissive oliguria (20 mL/h) is allowed since reduced urine output is a normal response to surgery (as a result of inappropriate secretion of antidiuretic hormone) and does not necessitate administration of a fluid bolus. Above all, anesthesiologists should acknowledge that fluid administration’s effects on a patient extend past the postanesthesia care unit, and the entire surgical team should be invested in the patient’s long-term recovery.

Our experience with ERAS

In 2011, Mayo Clinic was the first institution to implement enhanced recovery on a large scale in gynecologic surgery. We have subsequently made multiple pathway modifications in the spirit of continuous improvement (FIGURE 1).

For patients with ovarian cancer requiring extended procedures for cytoreduction via laparotomy (such as colon resection, splenectomy, diaphragm resection), enhanced recovery reduced the median hospital stay by 3 days, patient-controlled IV analgesia use by 88%, and postoperative opioid requirements by 90%.^9,10

At 48 hours after surgery, 40% of our patients require no opioids or tramadol, and epidurals are not utilized because of their effects on ambulation and the potential for hypotension. These reductions were met with stable to improved pain scores, a 60% decrease in nausea, and a 50% reduction in adynamic ileus.^9,10

Our initial efforts reduced 30-day costs of care by more than $850,000 in just 6 months, with savings of more than $7,600 for each patient undergoing a complex cytoreduction. Furthermore, these improvements allowed consolidation of our inpatient unit with those of other surgical specialties, serving higher volumes of patients within a smaller inpatient footprint. This contraction of inpatient services has accounted for an additional $1.1 million in savings every year since implementation (FIGURE 2).^9,10

Our group is not alone in realizing these benefits, and interest has intensified as demonstrated by the fact that the ERAS Society guidelines are among the all-time most downloaded articles in Gynecologic Oncology.^11,12 Although our research to demonstrate safety has focused on women undergoing complex oncologic operations, ERAS nevertheless hastens recovery, improves patient satisfaction, and adds value for all patients undergoing gynecologic surgery.

Continue to: Collateral improvements to practice...

Collateral improvements to practice

Clinical optimization using evidence-based practices such as enhanced recovery pathways can result in immediate patient benefit. Affecting such profound clinical improvements is energizing and creates a unique opportunity to transform the culture of the entire health care team. Irrespective of our provider roles (surgeon, anesthesiologist, nurse) or areas of interest (practice, research, education, leadership), we are united by a common purpose: to improve the human condition.¹³ Reaffirming this common purpose, through the collective effort involved in establishing a standardized enhanced recovery pathway, has allowed our practice and those of others to move beyond enhanced recovery and improve other areas of practice.

Other positive effects. The long-term collateral impact of this culture change at our institution is arguably more important than enhanced recovery itself. Examples of downstream impact include^14,15:

• 80% reduction in surgical site infection
• 50% reduction in anastomotic leaks
• 60% reduction in blood utilization for patients undergoing surgery for ovarian cancer.

Team-based pragmatic strategies. Additionally, our willingness to make decisions as a division rather than as individuals facilitated universal implementation of sentinel lymph node biopsy for patients with endometrial cancer and standardized imaging, testing, and surgical decision making for patients with ovarian and endometrial cancer.

The interventions associated with these improvements were not tested in a randomized fashion; however, rather than await perfect data, we made informed decisions based on imperfect data together with a commitment to continuous data review. We find this to be an effective strategy if our goal is to ensure that tomorrow’s outcomes will be better than yesterday’s. In this way, pragmatic trials can be extremely effective in rural settings and tertiary centers.

Barriers to innovation

The widely reported benefits of enhanced recovery beg the question, Why has enhanced recovery not been adopted universally as standard of care? The answer is multifaceted and highlights long-standing shortcomings in our health care system.

Most importantly, our health care system lacks a robust interface to link discovery of new techniques, treatments, and workflows to clinical practice. Perhaps the best example of this is the adoption of minimally invasive surgery (MIS) for endometrial cancer. Ten years have passed since randomized trials showed MIS has equivalent oncologic outcomes and superior recovery compared to laparotomy, yet in the United States less than 50% of women with endometrial cancer benefit.^16,17

However, even surgeons who are knowledgeable about recent innovations and genuinely wish to promote improvements may face near-insurmountable skepticism. Blind faith in our abilities and outcomes, overprotection of autonomy, close-mindedness, and satisfaction with the status quo are common responses to innovation and are the enemies of change. Resistance often comes from good intentions, but our desire to avoid complications may result in actions that could just as accurately be labeled superstitious as conservative. These observations suggest that developing methods to incorporate evidence-based practice into routine clinical use is the rate-limiting step in improving surgical quality.

Principles essential to change

Various methodologies have been described to manage change and facilitate implementation of new workflows and practices. Irrespective of the method used, including the more formal discipline of implementation science, at least 4 principles must be followed:

1. Teamwork. Mutual trust, mutual respect, and a sense of common purpose are minimum requirements for any successful initiative. Standardization is difficult or impossible without these elements. Thus, establishing a healthy team is the first step in implementing change.

2. Stakeholder analysis. Feedback from surgeons, nurses, residents, fellows, anesthesiologists, pharmacists, nurse anesthetists, and administrators is necessary to obtain diverse perspectives, facilitate engagement, and promote collaborative management. Negativity and resistance are common reactions to change, and it is particularly important to include those who are most skeptical in the stakeholder analysis to mitigate sabotage.

3. Concrete metrics. Success is possible only if defined a priori by specific and achievable goals. Counterbalances also are important to ensure that interventions do not have unintended consequences. Once a goal is met (for example, reduced hospital length of stay or costs), relevant metrics should be monitored after project completion for a minimum of 3 years to avoid regression to the pre-project state.

4. Leadership. The project champion responsible for the initiative must objectively facilitate all of the above and ensure excellent communication between stakeholders to nurture long-term engagement. Despite best efforts, if a minority of the group rejects compromise, this creates an opportunity to compare outcomes between those who do and do not accept the proposed change. Progress realized by early adopters may convince resistors to conform at a later time. Alternatively, the project champion also must have the insight to recognize when a proposed change is impossible at that point in time with that particular group. For example, our own initial attempts to implement enhanced recovery stalled in 2008, but they were successful 3 years later in a different environment.

Continue to: Although a discussion of leadership styles...

Although a discussion of leadership styles is beyond the scope of this article, in our experience, the most successful model is one of servant leadership that is team oriented rather than star dominated. Rather than being led by a single surgeon, each of the 4 quality improvement projects reviewed above (ERAS, and reductions in anastomotic leak, surgical site infection, and blood transfusion) that grew from enhanced recovery included trainees and was led by a different champion, encouraging teamwork and promoting career development. Such a model also supports the Accreditation Council for Graduate Medical Education’s emphasis on quality improvement education.

Our specialty is focusing now more intently on perioperative optimization, commonly referred to as enhanced recovery after surgery (ERAS), a concept championed first and most visibly by colorectal surgeons in the 1990s.¹ Both academic and nonacademic practices are challenging long-held beliefs about perioperative management.

The 3 tenets of ERAS

In multiple surgical specialties, proper implementation of 3 tenets—early feeding, perioperative euvolemia, and multimodal pain control—reduces the length of hospital stay, improves patient satisfaction, reduces complications, lowers health care costs, and most importantly hastens patient recovery.

1 Early feeding

Just as athletes hydrate and carbohydrate load prior to a competition, patients benefit if fluids and calories are not withheld in anticipation of a physiologically stressful surgical procedure. Similarly, modest benefit is associated with carbohydrate loading as a liquid supplement 2 hours before surgery.² The American Society of Anesthesiologists guidelines state that while solid foods should not be consumed after midnight before surgery, clear liquids safely may be withheld for only 2 hours prior to anesthesia induction, and systematic reviews have failed to show harm.^3,4 All patients, including those undergoing colonic resections, are allowed to eat a general diet as tolerated the evening before surgery, supplemented with caloric-dense nutritional supplements.

2 Multimodal pain control

Postsurgical pain is a top patient concern. Pain control is critical for rapid recovery; it helps avoid upregulation of the sympathetic axis and permits ambulation and resumption of normal activities. Although opioids relieve pain, they should not be considered a primary pain control approach.

Responding to the opioid epidemic, in 2015 the Centers for Disease Control and Prevention identified opioid overdose prevention as one of the top 5 public health challenges; notably, approximately 6% of patients will experience new, persistent opioid use following surgery.⁵ Optimal pain management therefore should provide effective pain relief while minimizing opioid use.

Preemptive oral acetaminophen, gabapentin, and celecoxib should be used routinely prior to incision; nonsteroidal anti-inflammatory drugs should be scheduled postoperatively. Even after a complex cytoreductive laparotomy, pain may be controlled with oral rather than intravenous (IV) medications in most patients, with opioid requirements averaging just 2 to 4 tablets of oxycodone in the first 48 hours after surgery, in our experience. The most critical need for pain medications occurs in the first 48 hours after surgery, which highlights the importance of local or regional analgesia. In one investigation, implementation of multimodal pain management that included incisional injection of liposomal bupivacaine reduced patient-controlled analgesia use to less than 5% after laparotomy.⁶ The need for opioids more than a week postoperatively is uncommon even after a laparotomy.

3 Perioperative euvolemia

Maintaining euvolemia is a central and underrecognized tenet of enhanced recovery pathways, and it facilitates the other 2 tenets of early feeding and optimal pain control. Overhydrated patients have more pain and prolonged recovery of bowel function. Unfortunately, euvolemia is the most difficult ERAS component to implement, requiring seamless communication between all members of the surgical team.

Continue to: Fluid therapy...

Fluid therapy should be respected as a pharmacologic agent with both benefits and risks. Recognizing that a single liter of lactated Ringer’s solution contains the sodium load of more than 30 bags of potato chips (and normal saline contains far more), one can imagine the impact of 10 L of solution on peripheral and bowel edema and on overall recovery. Importantly, euvolemia must be initiated during surgery. A meta-analysis of nearly 1,000 randomly assigned patients showed that benefits were limited when euvolemia was initiated in the postoperative period.⁷

When it comes to maintaining euvolemia, particular care must be taken to avoid erring toward hyperadherence. No difference in hospital length of stay, complications, or ileus was observed when patients were randomly assigned to goal-directed fluid therapy or standard practice.⁸ However, differences in the volume of fluid administered were relatively small, and while there was evidence of underhydration (likely responsible for acute kidney injury), there was no evidence of overhydration. For example, 4 L of fluid is likely superior to 15 L, but it may not be clinically different from 4.5 L. A threshold of fluid restriction is likely to be reached; that is, additional benefit is not achieved and, instead, detrimental effects may occur.

Rather than a specific directive, a more clinically relevant goal may be to replace insensible fluid losses and to maintain perfusion and blood pressure with the lowest volume possible. Note that estimation of fluid requirements is vastly simplified by omitting mechanical bowel preparation. Postoperatively, permissive oliguria (20 mL/h) is allowed since reduced urine output is a normal response to surgery (as a result of inappropriate secretion of antidiuretic hormone) and does not necessitate administration of a fluid bolus. Above all, anesthesiologists should acknowledge that fluid administration’s effects on a patient extend past the postanesthesia care unit, and the entire surgical team should be invested in the patient’s long-term recovery.

Our experience with ERAS

In 2011, Mayo Clinic was the first institution to implement enhanced recovery on a large scale in gynecologic surgery. We have subsequently made multiple pathway modifications in the spirit of continuous improvement (FIGURE 1).

For patients with ovarian cancer requiring extended procedures for cytoreduction via laparotomy (such as colon resection, splenectomy, diaphragm resection), enhanced recovery reduced the median hospital stay by 3 days, patient-controlled IV analgesia use by 88%, and postoperative opioid requirements by 90%.^9,10

At 48 hours after surgery, 40% of our patients require no opioids or tramadol, and epidurals are not utilized because of their effects on ambulation and the potential for hypotension. These reductions were met with stable to improved pain scores, a 60% decrease in nausea, and a 50% reduction in adynamic ileus.^9,10

Our initial efforts reduced 30-day costs of care by more than $850,000 in just 6 months, with savings of more than $7,600 for each patient undergoing a complex cytoreduction. Furthermore, these improvements allowed consolidation of our inpatient unit with those of other surgical specialties, serving higher volumes of patients within a smaller inpatient footprint. This contraction of inpatient services has accounted for an additional $1.1 million in savings every year since implementation (FIGURE 2).^9,10

Our group is not alone in realizing these benefits, and interest has intensified as demonstrated by the fact that the ERAS Society guidelines are among the all-time most downloaded articles in Gynecologic Oncology.^11,12 Although our research to demonstrate safety has focused on women undergoing complex oncologic operations, ERAS nevertheless hastens recovery, improves patient satisfaction, and adds value for all patients undergoing gynecologic surgery.

Continue to: Collateral improvements to practice...

Collateral improvements to practice

Clinical optimization using evidence-based practices such as enhanced recovery pathways can result in immediate patient benefit. Affecting such profound clinical improvements is energizing and creates a unique opportunity to transform the culture of the entire health care team. Irrespective of our provider roles (surgeon, anesthesiologist, nurse) or areas of interest (practice, research, education, leadership), we are united by a common purpose: to improve the human condition.¹³ Reaffirming this common purpose, through the collective effort involved in establishing a standardized enhanced recovery pathway, has allowed our practice and those of others to move beyond enhanced recovery and improve other areas of practice.

Other positive effects. The long-term collateral impact of this culture change at our institution is arguably more important than enhanced recovery itself. Examples of downstream impact include^14,15:

• 80% reduction in surgical site infection
• 50% reduction in anastomotic leaks
• 60% reduction in blood utilization for patients undergoing surgery for ovarian cancer.

Team-based pragmatic strategies. Additionally, our willingness to make decisions as a division rather than as individuals facilitated universal implementation of sentinel lymph node biopsy for patients with endometrial cancer and standardized imaging, testing, and surgical decision making for patients with ovarian and endometrial cancer.

The interventions associated with these improvements were not tested in a randomized fashion; however, rather than await perfect data, we made informed decisions based on imperfect data together with a commitment to continuous data review. We find this to be an effective strategy if our goal is to ensure that tomorrow’s outcomes will be better than yesterday’s. In this way, pragmatic trials can be extremely effective in rural settings and tertiary centers.

Barriers to innovation

The widely reported benefits of enhanced recovery beg the question, Why has enhanced recovery not been adopted universally as standard of care? The answer is multifaceted and highlights long-standing shortcomings in our health care system.

Most importantly, our health care system lacks a robust interface to link discovery of new techniques, treatments, and workflows to clinical practice. Perhaps the best example of this is the adoption of minimally invasive surgery (MIS) for endometrial cancer. Ten years have passed since randomized trials showed MIS has equivalent oncologic outcomes and superior recovery compared to laparotomy, yet in the United States less than 50% of women with endometrial cancer benefit.^16,17

However, even surgeons who are knowledgeable about recent innovations and genuinely wish to promote improvements may face near-insurmountable skepticism. Blind faith in our abilities and outcomes, overprotection of autonomy, close-mindedness, and satisfaction with the status quo are common responses to innovation and are the enemies of change. Resistance often comes from good intentions, but our desire to avoid complications may result in actions that could just as accurately be labeled superstitious as conservative. These observations suggest that developing methods to incorporate evidence-based practice into routine clinical use is the rate-limiting step in improving surgical quality.

Principles essential to change

Various methodologies have been described to manage change and facilitate implementation of new workflows and practices. Irrespective of the method used, including the more formal discipline of implementation science, at least 4 principles must be followed:

1. Teamwork. Mutual trust, mutual respect, and a sense of common purpose are minimum requirements for any successful initiative. Standardization is difficult or impossible without these elements. Thus, establishing a healthy team is the first step in implementing change.

2. Stakeholder analysis. Feedback from surgeons, nurses, residents, fellows, anesthesiologists, pharmacists, nurse anesthetists, and administrators is necessary to obtain diverse perspectives, facilitate engagement, and promote collaborative management. Negativity and resistance are common reactions to change, and it is particularly important to include those who are most skeptical in the stakeholder analysis to mitigate sabotage.

3. Concrete metrics. Success is possible only if defined a priori by specific and achievable goals. Counterbalances also are important to ensure that interventions do not have unintended consequences. Once a goal is met (for example, reduced hospital length of stay or costs), relevant metrics should be monitored after project completion for a minimum of 3 years to avoid regression to the pre-project state.

4. Leadership. The project champion responsible for the initiative must objectively facilitate all of the above and ensure excellent communication between stakeholders to nurture long-term engagement. Despite best efforts, if a minority of the group rejects compromise, this creates an opportunity to compare outcomes between those who do and do not accept the proposed change. Progress realized by early adopters may convince resistors to conform at a later time. Alternatively, the project champion also must have the insight to recognize when a proposed change is impossible at that point in time with that particular group. For example, our own initial attempts to implement enhanced recovery stalled in 2008, but they were successful 3 years later in a different environment.

Continue to: Although a discussion of leadership styles...

Although a discussion of leadership styles is beyond the scope of this article, in our experience, the most successful model is one of servant leadership that is team oriented rather than star dominated. Rather than being led by a single surgeon, each of the 4 quality improvement projects reviewed above (ERAS, and reductions in anastomotic leak, surgical site infection, and blood transfusion) that grew from enhanced recovery included trainees and was led by a different champion, encouraging teamwork and promoting career development. Such a model also supports the Accreditation Council for Graduate Medical Education’s emphasis on quality improvement education.

Prenatal diagnosis of genetic anomalies is important for diagnosing lethal genetic conditions before birth. It can provide information for parents regarding pregnancy options and allow for recurrence risk counseling and the potential use of preimplantation genetic testing in the next pregnancy. For decades, a karyotype was used to analyze amniocentesis and chorionic villus sampling specimens; in recent years, chromosomal microarray analysis provides more information about significant chromosomal abnormalities, including microdeletions and microduplications. However, microarrays also have limitations, as they do not identify base pair changes associated with single-gene disorders.

The advent of next-generation sequencing has substantially reduced the cost of DNA sequencing. Whole genome sequencing (WGS) can sequence the entire genome— both the coding (exonic) and noncoding (intronic) regions—while exome sequencing analyzes only the protein-coding exons, which make up 1% to 2% of the genome and about 85% of the protein-coding genes associated with known human disease. Exome sequencing increasingly is used in cases of suspected genetic disorders when other tests have been unrevealing.

In this Update, we review recent reports of prenatal exome sequencing, including studies exploring the yield in fetuses with structural anomalies; the importance of prenatal phenotyping; the perspectives of parents and health care professionals who were involved in prenatal exome sequencing studies; and a summary of a joint position statement from 3 societies regarding prenatal sequencing.

Prenatal whole exome sequencing has potential utility, with some limitations 

Petrovski S, Aggarwal V, Giordano JL, et al. Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study. Lancet. 2019;393:758-767. 
 

Lord J, McMullan DJ, Eberhardt RY, et al; for the Prenatal Assessment of Genomes and Exomes Consortium. Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study. Lancet. 2019;393:747-757. 

Exome sequencing has been shown to identify an underlying genetic cause in 25% to 30% of children with an undiagnosed suspected genetic disorder. Two studies recently published in the Lancet sought to determine the incremental diagnostic yield of prenatal whole exome sequencing (WES) in the setting of fetal structural anomalies when karyotype and microarray results were normal. 

Continue to: Details of the studies...

In a prospective cohort study by Petrovski and colleagues, DNA samples from 234 fetuses with a structural anomaly (identified on ultrasonography) and both parents (parent-fetus "trios") were used for analysis. WES identified diagnostic genetic variants in 24 trios (10%). An additional 46 (20%) had variants that indicated pathogenicity but without sufficient evidence to be considered diagnostic. 

The anomalies with the highest frequency of a genetic diagnosis were lymphatic, 24%; skeletal, 24%; central nervous system, 22%; and renal, 16%; while cardiac anomalies had the lowest yield at 5%. 

In another prospective cohort study, known as the Prenatal Assessment of Genomes and Exomes (PAGE), Lord and colleagues sequenced DNA samples from 610 parent-fetus trios, but they restricted sequencing to a predefined list of 1,628 genes. Diagnostic genetic variants were identified in 52 fetuses (8.5%), while 24 (3.9%) had a variant of uncertain significance that was thought to be of potential clinical usefulness. 

Fetuses with multiple anomalies had the highest genetic yield (15.4%), followed by skeletal (15.4%) and cardiac anomalies (11.1%), with the lowest yield in fetuses with isolated increased nuchal translucency (3.2%). 

Diagnostic yield is high, but prenatal utility is limited 

Both studies showed a clinically significant diagnostic yield of 8% to 10% for prenatal exome sequencing in cases of fetal structural anomalies with normal karyotype and microarray testing. While this yield demonstrates the utility of prenatal exome sequencing, it is significantly lower than what has been reported in postnatal studies. One of the reasons for this is the inherent limitation of prenatal phenotyping (discussed below). 

The importance of prenatal phenotyping 

Aarabi M, Sniezek O, Jiang H, et al. Importance of complete phenotyping in prenatal whole exome sequencing. Hum Genet. 2018;137:175-181. 

In postnatal exome sequencing, the physical exam, imaging findings, and laboratory results are components of the phenotype that are used to interpret the sequencing data. Prenatal phenotyping, however, is limited to the use of fetal ultrasonography and, occasionally, the addition of magnetic resonance imaging. Prenatal phenotyping is without the benefit of an exam to detect more subtle anomalies or functional status, such as developmental delay, seizures, or failure to thrive. 

When a structural anomaly is identified on prenatal ultrasonography, it is especially important that detailed imaging be undertaken to detect other anomalies, including more subtle facial features and dysmorphology. 

Value of reanalyzing exome sequencing data 

Aarabi and colleagues conducted a retrospective study of 20 fetuses with structural anomalies and normal karyotype and microarray. They performed trio exome sequencing first using information available only prenatally and then conducted a reanalysis using information available after delivery. 

With prenatal phenotyping only, the investigators identified no pathogenic, or likely pathogenic, variants. On reanalysis of combined prenatal and postnatal findings, however, they identified pathogenic variants in 20% of cases. 

Significance of the findings 

This study highlights both the importance of a careful, detailed fetal ultrasonography study and the possible additional benefit of a postnatal examination (such as an autopsy) in order to yield improved results. In addition, the authors noted that the development of a prenatal phenotype-genotype database would significantly help exome sequencing interpretation in the prenatal setting.

Social impact of WES: Parent and provider perspectives 

Wou K, Weitz T, McCormack C, et al. Parental perceptions of prenatal whole exome sequencing (PPPWES) study. Prenat Diagn. 2018;38:801-811. 

Horn R, Parker M. Health professionals' and researchers' perspectives on prenatal whole genome and exome sequencing: 'We can't shut the door now, the genie's out, we need to refine it.' PLoS One. 2018;13:e0204158. 

As health care providers enter a new era of prenatal genetic testing with exome sequencing, it is crucial to the path forward that we obtain perspectives from the parents and providers who participated in these studies. Notably, in both of the previously discussed Lancet reports, the authors interviewed the participants to discuss the challenges involved and identify strategies for improving future testing. 

Continue to: What parents want...

To ascertain the perceptions of couples who underwent prenatal WES, Wou and colleagues conducted semi-structured interviews with participants from the Fetal Sequencing Study regarding their experience. They interviewed 29 parents from 17 pregnancies, including a mix of those who had pathogenic prenatal results, terminated prior to receiving the results, and had normal results. 
 

Expressed feelings and desires. Parents recalled feelings of anxiety and stress around the time of diagnosis and the need for help with coping while awaiting results. The majority of parents reported that they would like to be told about uncertain results, but that desire decreased as the certainty of results decreased. 

Parents were overall satisfied with the prenatal genetic testing experience, but they added that they would have liked to receive written materials beforehand and a written report of the test results (including negative cases). They also would like to have connected with other families with similar experiences, to have received results sooner, and to have an in-person meeting after telephone disclosure of the results. 

Health professionals articulate complexity of prenatal genomics 

In a qualitative interview study to explore critical issues involved in the clinical practice use of prenatal genomics, Horn and Parker conducted interviews with 20 health care professionals who were involved in the previously described PAGE trial. Patient recruiters, midwives, genetic counselors, research assistants, and laboratory staff were included. 

Interviewees cited numerous challenges involved in their day-to-day work with prenatal whole genome and exome sequencing, including: 

• the complexity of achieving valid parental consent at a time of vulnerability 
• management of parent expectations  
• transmitting and comprehending complex information 
• the usefulness of information 
• the difficulty of a long turnaround time for study results. 

All the interviewees agreed that prenatal exome sequencing studies contribute to knowledge generation and the advancement of technology. 

The authors concluded that an appropriate next step would be the development of appropriate guidelines for good ethical practice that address the concerns encountered in genomics clinical practice.

Societies offer guidance on using genome and exome sequencing 

International Society for Prenatal Diagnosis, Society for Maternal and Fetal Medicine, Perinatal Quality Foundation. Joint Position Statement from the International Society for Prenatal Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality Foundation (PQF) on the use of genome-wide sequencing for fetal diagnosis. Prenat Diagn. 2018;38:6-9. 

In response to the rapid integration of exome sequencing for genetic diagnosis, several professional societies—the International Society for Prenatal Diagnosis, Society for Maternal Fetal Medicine, and Perinatal Quality Foundation—issued a joint statement addressing the clinical use of prenatal diagnostic genome wide sequencing, including exome sequencing. 

Continue to: Guidance at a glance...

The societies' recommendations are summarized as follows: 

• Exome sequencing is best done as a trio analysis, with fetal and both parental samples sequenced and analyzed together. 
• Extensive pretest education, counseling, and informed consent, as well as posttest counseling, are essential. This should include:  

—the types of results to be conveyed (variants that are pathogenic, likely pathogenic, of uncertain significance, likely benign, and benign) 
—the possibility that results will not be obtained or may not be available before the birth of the fetus 
—realistic expectations regarding the likelihood that a significant result will be obtained 
—the timeframe to results 
—the option to include or exclude in the results incidental or secondary findings (such as an unexpected childhood disorder, cancer susceptibility genes, adult-onset disorders) 
—the possibility of uncovering nonpaternity or consanguinity 
—the potential reanalysis of results over time 
—how data are stored, who has access, and for what purpose. 

• Fetal sequencing may be beneficial in the following scenarios: 

—multiple fetal anomalies or a single major anomaly suggestive of a genetic disorder, when the microarray is negative 
—no microarray result is available, but the fetus exhibits a pattern of anomalies strongly suggestive of a single-gene disorder  
—a prior undiagnosed fetus (or child) with anomalies suggestive of a genetic etiology, and with similar anomalies in the current pregnancy, with normal karyotype or microarray. Providers also can consider sequencing samples from both parents prior to preimplantation genetic testing to check for shared carrier status for autosomal recessive mutations, although obtaining exome sequencing from the prior affected fetus (or child) is ideal. 
—history of recurrent stillbirths of unknown etiology, with a recurrent pattern of anomalies in the current pregnancy, with normal karyotype or microarray. 

• Interpretation of results should be done using a multidisciplinary team-based approach, including clinical scientists, geneticists, genetic counselors, and experts in prenatal diagnosis. 
• Where possible and after informed consent, reanalysis of results should be undertaken if a future pregnancy is planned or ongoing, and a significant amount of time has elapsed since the time the result was last reported. 
• Parents should be given a written report of test results. 

Summary

Exome sequencing is increasingly becoming mainstream in postnatal genetic testing, and it is emerging as the newest diagnostic frontier in prenatal genetic testing. However, there are limitations to prenatal exome sequencing, including issues with consent at a vulnerable time for parents, limited information available regarding the phenotype, and results that may not be available before the birth of a fetus. Providers should be familiar with the indications for testing, the possible results, the limitations of prenatal phenotyping, and the implications for future pregnancies. 
 

Prenatal diagnosis of genetic anomalies is important for diagnosing lethal genetic conditions before birth. It can provide information for parents regarding pregnancy options and allow for recurrence risk counseling and the potential use of preimplantation genetic testing in the next pregnancy. For decades, a karyotype was used to analyze amniocentesis and chorionic villus sampling specimens; in recent years, chromosomal microarray analysis provides more information about significant chromosomal abnormalities, including microdeletions and microduplications. However, microarrays also have limitations, as they do not identify base pair changes associated with single-gene disorders.

The advent of next-generation sequencing has substantially reduced the cost of DNA sequencing. Whole genome sequencing (WGS) can sequence the entire genome— both the coding (exonic) and noncoding (intronic) regions—while exome sequencing analyzes only the protein-coding exons, which make up 1% to 2% of the genome and about 85% of the protein-coding genes associated with known human disease. Exome sequencing increasingly is used in cases of suspected genetic disorders when other tests have been unrevealing.

In this Update, we review recent reports of prenatal exome sequencing, including studies exploring the yield in fetuses with structural anomalies; the importance of prenatal phenotyping; the perspectives of parents and health care professionals who were involved in prenatal exome sequencing studies; and a summary of a joint position statement from 3 societies regarding prenatal sequencing.

Prenatal whole exome sequencing has potential utility, with some limitations 

Petrovski S, Aggarwal V, Giordano JL, et al. Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study. Lancet. 2019;393:758-767. 
 

Lord J, McMullan DJ, Eberhardt RY, et al; for the Prenatal Assessment of Genomes and Exomes Consortium. Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study. Lancet. 2019;393:747-757. 

Exome sequencing has been shown to identify an underlying genetic cause in 25% to 30% of children with an undiagnosed suspected genetic disorder. Two studies recently published in the Lancet sought to determine the incremental diagnostic yield of prenatal whole exome sequencing (WES) in the setting of fetal structural anomalies when karyotype and microarray results were normal. 

Continue to: Details of the studies...

In a prospective cohort study by Petrovski and colleagues, DNA samples from 234 fetuses with a structural anomaly (identified on ultrasonography) and both parents (parent-fetus "trios") were used for analysis. WES identified diagnostic genetic variants in 24 trios (10%). An additional 46 (20%) had variants that indicated pathogenicity but without sufficient evidence to be considered diagnostic. 

The anomalies with the highest frequency of a genetic diagnosis were lymphatic, 24%; skeletal, 24%; central nervous system, 22%; and renal, 16%; while cardiac anomalies had the lowest yield at 5%. 

In another prospective cohort study, known as the Prenatal Assessment of Genomes and Exomes (PAGE), Lord and colleagues sequenced DNA samples from 610 parent-fetus trios, but they restricted sequencing to a predefined list of 1,628 genes. Diagnostic genetic variants were identified in 52 fetuses (8.5%), while 24 (3.9%) had a variant of uncertain significance that was thought to be of potential clinical usefulness. 

Fetuses with multiple anomalies had the highest genetic yield (15.4%), followed by skeletal (15.4%) and cardiac anomalies (11.1%), with the lowest yield in fetuses with isolated increased nuchal translucency (3.2%). 

Diagnostic yield is high, but prenatal utility is limited 

Both studies showed a clinically significant diagnostic yield of 8% to 10% for prenatal exome sequencing in cases of fetal structural anomalies with normal karyotype and microarray testing. While this yield demonstrates the utility of prenatal exome sequencing, it is significantly lower than what has been reported in postnatal studies. One of the reasons for this is the inherent limitation of prenatal phenotyping (discussed below). 

The importance of prenatal phenotyping 

Aarabi M, Sniezek O, Jiang H, et al. Importance of complete phenotyping in prenatal whole exome sequencing. Hum Genet. 2018;137:175-181. 

In postnatal exome sequencing, the physical exam, imaging findings, and laboratory results are components of the phenotype that are used to interpret the sequencing data. Prenatal phenotyping, however, is limited to the use of fetal ultrasonography and, occasionally, the addition of magnetic resonance imaging. Prenatal phenotyping is without the benefit of an exam to detect more subtle anomalies or functional status, such as developmental delay, seizures, or failure to thrive. 

When a structural anomaly is identified on prenatal ultrasonography, it is especially important that detailed imaging be undertaken to detect other anomalies, including more subtle facial features and dysmorphology. 

Value of reanalyzing exome sequencing data 

Aarabi and colleagues conducted a retrospective study of 20 fetuses with structural anomalies and normal karyotype and microarray. They performed trio exome sequencing first using information available only prenatally and then conducted a reanalysis using information available after delivery. 

With prenatal phenotyping only, the investigators identified no pathogenic, or likely pathogenic, variants. On reanalysis of combined prenatal and postnatal findings, however, they identified pathogenic variants in 20% of cases. 

Significance of the findings 

This study highlights both the importance of a careful, detailed fetal ultrasonography study and the possible additional benefit of a postnatal examination (such as an autopsy) in order to yield improved results. In addition, the authors noted that the development of a prenatal phenotype-genotype database would significantly help exome sequencing interpretation in the prenatal setting.

Social impact of WES: Parent and provider perspectives 

Wou K, Weitz T, McCormack C, et al. Parental perceptions of prenatal whole exome sequencing (PPPWES) study. Prenat Diagn. 2018;38:801-811. 

Horn R, Parker M. Health professionals' and researchers' perspectives on prenatal whole genome and exome sequencing: 'We can't shut the door now, the genie's out, we need to refine it.' PLoS One. 2018;13:e0204158. 

As health care providers enter a new era of prenatal genetic testing with exome sequencing, it is crucial to the path forward that we obtain perspectives from the parents and providers who participated in these studies. Notably, in both of the previously discussed Lancet reports, the authors interviewed the participants to discuss the challenges involved and identify strategies for improving future testing. 

Continue to: What parents want...

To ascertain the perceptions of couples who underwent prenatal WES, Wou and colleagues conducted semi-structured interviews with participants from the Fetal Sequencing Study regarding their experience. They interviewed 29 parents from 17 pregnancies, including a mix of those who had pathogenic prenatal results, terminated prior to receiving the results, and had normal results. 
 

Expressed feelings and desires. Parents recalled feelings of anxiety and stress around the time of diagnosis and the need for help with coping while awaiting results. The majority of parents reported that they would like to be told about uncertain results, but that desire decreased as the certainty of results decreased. 

Parents were overall satisfied with the prenatal genetic testing experience, but they added that they would have liked to receive written materials beforehand and a written report of the test results (including negative cases). They also would like to have connected with other families with similar experiences, to have received results sooner, and to have an in-person meeting after telephone disclosure of the results. 

Health professionals articulate complexity of prenatal genomics 

In a qualitative interview study to explore critical issues involved in the clinical practice use of prenatal genomics, Horn and Parker conducted interviews with 20 health care professionals who were involved in the previously described PAGE trial. Patient recruiters, midwives, genetic counselors, research assistants, and laboratory staff were included. 

Interviewees cited numerous challenges involved in their day-to-day work with prenatal whole genome and exome sequencing, including: 

• the complexity of achieving valid parental consent at a time of vulnerability 
• management of parent expectations  
• transmitting and comprehending complex information 
• the usefulness of information 
• the difficulty of a long turnaround time for study results. 

All the interviewees agreed that prenatal exome sequencing studies contribute to knowledge generation and the advancement of technology. 

The authors concluded that an appropriate next step would be the development of appropriate guidelines for good ethical practice that address the concerns encountered in genomics clinical practice.

Societies offer guidance on using genome and exome sequencing 

International Society for Prenatal Diagnosis, Society for Maternal and Fetal Medicine, Perinatal Quality Foundation. Joint Position Statement from the International Society for Prenatal Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality Foundation (PQF) on the use of genome-wide sequencing for fetal diagnosis. Prenat Diagn. 2018;38:6-9. 

In response to the rapid integration of exome sequencing for genetic diagnosis, several professional societies—the International Society for Prenatal Diagnosis, Society for Maternal Fetal Medicine, and Perinatal Quality Foundation—issued a joint statement addressing the clinical use of prenatal diagnostic genome wide sequencing, including exome sequencing. 

Continue to: Guidance at a glance...

The societies' recommendations are summarized as follows: 

• Exome sequencing is best done as a trio analysis, with fetal and both parental samples sequenced and analyzed together. 
• Extensive pretest education, counseling, and informed consent, as well as posttest counseling, are essential. This should include:  

—the types of results to be conveyed (variants that are pathogenic, likely pathogenic, of uncertain significance, likely benign, and benign) 
—the possibility that results will not be obtained or may not be available before the birth of the fetus 
—realistic expectations regarding the likelihood that a significant result will be obtained 
—the timeframe to results 
—the option to include or exclude in the results incidental or secondary findings (such as an unexpected childhood disorder, cancer susceptibility genes, adult-onset disorders) 
—the possibility of uncovering nonpaternity or consanguinity 
—the potential reanalysis of results over time 
—how data are stored, who has access, and for what purpose. 

• Fetal sequencing may be beneficial in the following scenarios: 

—multiple fetal anomalies or a single major anomaly suggestive of a genetic disorder, when the microarray is negative 
—no microarray result is available, but the fetus exhibits a pattern of anomalies strongly suggestive of a single-gene disorder  
—a prior undiagnosed fetus (or child) with anomalies suggestive of a genetic etiology, and with similar anomalies in the current pregnancy, with normal karyotype or microarray. Providers also can consider sequencing samples from both parents prior to preimplantation genetic testing to check for shared carrier status for autosomal recessive mutations, although obtaining exome sequencing from the prior affected fetus (or child) is ideal. 
—history of recurrent stillbirths of unknown etiology, with a recurrent pattern of anomalies in the current pregnancy, with normal karyotype or microarray. 

• Interpretation of results should be done using a multidisciplinary team-based approach, including clinical scientists, geneticists, genetic counselors, and experts in prenatal diagnosis. 
• Where possible and after informed consent, reanalysis of results should be undertaken if a future pregnancy is planned or ongoing, and a significant amount of time has elapsed since the time the result was last reported. 
• Parents should be given a written report of test results. 

Summary

Exome sequencing is increasingly becoming mainstream in postnatal genetic testing, and it is emerging as the newest diagnostic frontier in prenatal genetic testing. However, there are limitations to prenatal exome sequencing, including issues with consent at a vulnerable time for parents, limited information available regarding the phenotype, and results that may not be available before the birth of a fetus. Providers should be familiar with the indications for testing, the possible results, the limitations of prenatal phenotyping, and the implications for future pregnancies. 
 

Prenatal diagnosis of genetic anomalies is important for diagnosing lethal genetic conditions before birth. It can provide information for parents regarding pregnancy options and allow for recurrence risk counseling and the potential use of preimplantation genetic testing in the next pregnancy. For decades, a karyotype was used to analyze amniocentesis and chorionic villus sampling specimens; in recent years, chromosomal microarray analysis provides more information about significant chromosomal abnormalities, including microdeletions and microduplications. However, microarrays also have limitations, as they do not identify base pair changes associated with single-gene disorders.

The advent of next-generation sequencing has substantially reduced the cost of DNA sequencing. Whole genome sequencing (WGS) can sequence the entire genome— both the coding (exonic) and noncoding (intronic) regions—while exome sequencing analyzes only the protein-coding exons, which make up 1% to 2% of the genome and about 85% of the protein-coding genes associated with known human disease. Exome sequencing increasingly is used in cases of suspected genetic disorders when other tests have been unrevealing.

In this Update, we review recent reports of prenatal exome sequencing, including studies exploring the yield in fetuses with structural anomalies; the importance of prenatal phenotyping; the perspectives of parents and health care professionals who were involved in prenatal exome sequencing studies; and a summary of a joint position statement from 3 societies regarding prenatal sequencing.

Prenatal whole exome sequencing has potential utility, with some limitations 

Petrovski S, Aggarwal V, Giordano JL, et al. Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study. Lancet. 2019;393:758-767. 
 

Lord J, McMullan DJ, Eberhardt RY, et al; for the Prenatal Assessment of Genomes and Exomes Consortium. Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study. Lancet. 2019;393:747-757. 

Exome sequencing has been shown to identify an underlying genetic cause in 25% to 30% of children with an undiagnosed suspected genetic disorder. Two studies recently published in the Lancet sought to determine the incremental diagnostic yield of prenatal whole exome sequencing (WES) in the setting of fetal structural anomalies when karyotype and microarray results were normal. 

Continue to: Details of the studies...

In a prospective cohort study by Petrovski and colleagues, DNA samples from 234 fetuses with a structural anomaly (identified on ultrasonography) and both parents (parent-fetus "trios") were used for analysis. WES identified diagnostic genetic variants in 24 trios (10%). An additional 46 (20%) had variants that indicated pathogenicity but without sufficient evidence to be considered diagnostic. 

The anomalies with the highest frequency of a genetic diagnosis were lymphatic, 24%; skeletal, 24%; central nervous system, 22%; and renal, 16%; while cardiac anomalies had the lowest yield at 5%. 

In another prospective cohort study, known as the Prenatal Assessment of Genomes and Exomes (PAGE), Lord and colleagues sequenced DNA samples from 610 parent-fetus trios, but they restricted sequencing to a predefined list of 1,628 genes. Diagnostic genetic variants were identified in 52 fetuses (8.5%), while 24 (3.9%) had a variant of uncertain significance that was thought to be of potential clinical usefulness. 

Fetuses with multiple anomalies had the highest genetic yield (15.4%), followed by skeletal (15.4%) and cardiac anomalies (11.1%), with the lowest yield in fetuses with isolated increased nuchal translucency (3.2%). 

Diagnostic yield is high, but prenatal utility is limited 

Both studies showed a clinically significant diagnostic yield of 8% to 10% for prenatal exome sequencing in cases of fetal structural anomalies with normal karyotype and microarray testing. While this yield demonstrates the utility of prenatal exome sequencing, it is significantly lower than what has been reported in postnatal studies. One of the reasons for this is the inherent limitation of prenatal phenotyping (discussed below). 

The importance of prenatal phenotyping 

Aarabi M, Sniezek O, Jiang H, et al. Importance of complete phenotyping in prenatal whole exome sequencing. Hum Genet. 2018;137:175-181. 

In postnatal exome sequencing, the physical exam, imaging findings, and laboratory results are components of the phenotype that are used to interpret the sequencing data. Prenatal phenotyping, however, is limited to the use of fetal ultrasonography and, occasionally, the addition of magnetic resonance imaging. Prenatal phenotyping is without the benefit of an exam to detect more subtle anomalies or functional status, such as developmental delay, seizures, or failure to thrive. 

When a structural anomaly is identified on prenatal ultrasonography, it is especially important that detailed imaging be undertaken to detect other anomalies, including more subtle facial features and dysmorphology. 

Value of reanalyzing exome sequencing data 

Aarabi and colleagues conducted a retrospective study of 20 fetuses with structural anomalies and normal karyotype and microarray. They performed trio exome sequencing first using information available only prenatally and then conducted a reanalysis using information available after delivery. 

With prenatal phenotyping only, the investigators identified no pathogenic, or likely pathogenic, variants. On reanalysis of combined prenatal and postnatal findings, however, they identified pathogenic variants in 20% of cases. 

Significance of the findings 

This study highlights both the importance of a careful, detailed fetal ultrasonography study and the possible additional benefit of a postnatal examination (such as an autopsy) in order to yield improved results. In addition, the authors noted that the development of a prenatal phenotype-genotype database would significantly help exome sequencing interpretation in the prenatal setting.

Social impact of WES: Parent and provider perspectives 

Wou K, Weitz T, McCormack C, et al. Parental perceptions of prenatal whole exome sequencing (PPPWES) study. Prenat Diagn. 2018;38:801-811. 

Horn R, Parker M. Health professionals' and researchers' perspectives on prenatal whole genome and exome sequencing: 'We can't shut the door now, the genie's out, we need to refine it.' PLoS One. 2018;13:e0204158. 

As health care providers enter a new era of prenatal genetic testing with exome sequencing, it is crucial to the path forward that we obtain perspectives from the parents and providers who participated in these studies. Notably, in both of the previously discussed Lancet reports, the authors interviewed the participants to discuss the challenges involved and identify strategies for improving future testing. 

Continue to: What parents want...

To ascertain the perceptions of couples who underwent prenatal WES, Wou and colleagues conducted semi-structured interviews with participants from the Fetal Sequencing Study regarding their experience. They interviewed 29 parents from 17 pregnancies, including a mix of those who had pathogenic prenatal results, terminated prior to receiving the results, and had normal results. 
 

Expressed feelings and desires. Parents recalled feelings of anxiety and stress around the time of diagnosis and the need for help with coping while awaiting results. The majority of parents reported that they would like to be told about uncertain results, but that desire decreased as the certainty of results decreased. 

Parents were overall satisfied with the prenatal genetic testing experience, but they added that they would have liked to receive written materials beforehand and a written report of the test results (including negative cases). They also would like to have connected with other families with similar experiences, to have received results sooner, and to have an in-person meeting after telephone disclosure of the results. 

Health professionals articulate complexity of prenatal genomics 

In a qualitative interview study to explore critical issues involved in the clinical practice use of prenatal genomics, Horn and Parker conducted interviews with 20 health care professionals who were involved in the previously described PAGE trial. Patient recruiters, midwives, genetic counselors, research assistants, and laboratory staff were included. 

Interviewees cited numerous challenges involved in their day-to-day work with prenatal whole genome and exome sequencing, including: 

• the complexity of achieving valid parental consent at a time of vulnerability 
• management of parent expectations  
• transmitting and comprehending complex information 
• the usefulness of information 
• the difficulty of a long turnaround time for study results. 

All the interviewees agreed that prenatal exome sequencing studies contribute to knowledge generation and the advancement of technology. 

The authors concluded that an appropriate next step would be the development of appropriate guidelines for good ethical practice that address the concerns encountered in genomics clinical practice.

Societies offer guidance on using genome and exome sequencing 

International Society for Prenatal Diagnosis, Society for Maternal and Fetal Medicine, Perinatal Quality Foundation. Joint Position Statement from the International Society for Prenatal Diagnosis (ISPD), the Society for Maternal Fetal Medicine (SMFM), and the Perinatal Quality Foundation (PQF) on the use of genome-wide sequencing for fetal diagnosis. Prenat Diagn. 2018;38:6-9. 

In response to the rapid integration of exome sequencing for genetic diagnosis, several professional societies—the International Society for Prenatal Diagnosis, Society for Maternal Fetal Medicine, and Perinatal Quality Foundation—issued a joint statement addressing the clinical use of prenatal diagnostic genome wide sequencing, including exome sequencing. 

Continue to: Guidance at a glance...

The societies' recommendations are summarized as follows: 

• Exome sequencing is best done as a trio analysis, with fetal and both parental samples sequenced and analyzed together. 
• Extensive pretest education, counseling, and informed consent, as well as posttest counseling, are essential. This should include:  

—the types of results to be conveyed (variants that are pathogenic, likely pathogenic, of uncertain significance, likely benign, and benign) 
—the possibility that results will not be obtained or may not be available before the birth of the fetus 
—realistic expectations regarding the likelihood that a significant result will be obtained 
—the timeframe to results 
—the option to include or exclude in the results incidental or secondary findings (such as an unexpected childhood disorder, cancer susceptibility genes, adult-onset disorders) 
—the possibility of uncovering nonpaternity or consanguinity 
—the potential reanalysis of results over time 
—how data are stored, who has access, and for what purpose. 

• Fetal sequencing may be beneficial in the following scenarios: 

—multiple fetal anomalies or a single major anomaly suggestive of a genetic disorder, when the microarray is negative 
—no microarray result is available, but the fetus exhibits a pattern of anomalies strongly suggestive of a single-gene disorder  
—a prior undiagnosed fetus (or child) with anomalies suggestive of a genetic etiology, and with similar anomalies in the current pregnancy, with normal karyotype or microarray. Providers also can consider sequencing samples from both parents prior to preimplantation genetic testing to check for shared carrier status for autosomal recessive mutations, although obtaining exome sequencing from the prior affected fetus (or child) is ideal. 
—history of recurrent stillbirths of unknown etiology, with a recurrent pattern of anomalies in the current pregnancy, with normal karyotype or microarray. 

• Interpretation of results should be done using a multidisciplinary team-based approach, including clinical scientists, geneticists, genetic counselors, and experts in prenatal diagnosis. 
• Where possible and after informed consent, reanalysis of results should be undertaken if a future pregnancy is planned or ongoing, and a significant amount of time has elapsed since the time the result was last reported. 
• Parents should be given a written report of test results. 

Summary

Exome sequencing is increasingly becoming mainstream in postnatal genetic testing, and it is emerging as the newest diagnostic frontier in prenatal genetic testing. However, there are limitations to prenatal exome sequencing, including issues with consent at a vulnerable time for parents, limited information available regarding the phenotype, and results that may not be available before the birth of a fetus. Providers should be familiar with the indications for testing, the possible results, the limitations of prenatal phenotyping, and the implications for future pregnancies. 
 

EXPERT COMMENTARY

Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F, et al. Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study. BMJ. 2019;364:1665.

Alzheimer disease represents the most common cause of dementia. Although sex hormones may play a role in the etiology of AD in women, studies addressing the impact of menopausal HT on risk of AD have conflicting findings.

Finnish researchers Savolainen-Peltonen and colleagues aimed to compare postmenopausal HT use in women with and without AD. They used national drug and population registries to identify patients with AD, control women without a diagnosis of AD, and data on postmenopausal HT use.

Details of the study

In Finland, reimbursement for treatment related to AD requires cognitive testing, brain imaging, and a statement from a specialist physician. Using national records, the study investigators identified 84,739 women with a diagnosis of AD during the years 1999–2013 and the same number of control women (without AD) during the same period. A national drug reimbursement registry was used to identify HT use from the year 1994.

Findings. Women diagnosed with AD were more likely to have been current or former users of systemic HT than controls (18.6% vs 17.0%, P<.001). The odds ratios (ORs) for AD were 1.09 for the estradiol-only group and 1.17 for the estrogen-progestin group (P<.05 for both comparisons).

Initiation of HT prior to age 60 was less common among AD cases than controls (P = .006). As a continuous variable, age was not a determinant for disease risk in estradiol-only users (OR, 1.0), estrogen-progestin users (OR, 1.0), or any HT use (OR, 1.0).

The exclusive use of vaginal estrogen therapy was not associated with an elevated risk of AD (OR, 0.99).

Study strengths and limitations

This study on the association between HT and AD included a very large number of participants from a national population registry, and the use of HT was objectively determined from a controlled registry (not self-reported). In addition, AD was accurately diagnosed and differentiated from other forms of dementia.

Limitations of the study include the lack of baseline demographic data for AD risk factors for both HT users and controls. Further, an increased risk of AD may have been a cause for HT use and not a consequence, given that initial cognitive impairments may occur 7 to 8 years prior to AD diagnosis and the possibility exists that such women may have sought help for cognitive symptoms from HT. In addition, the lack of brain imaging or neurologic examination to exclude AD might also account for undiagnosed disease in controls. The authors noted that they were unable to compare the use of oral and transdermal HT preparations or the use of cyclic and continuous estrogen-progestin therapy.

EXPERT COMMENTARY

Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F, et al. Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study. BMJ. 2019;364:1665.

Alzheimer disease represents the most common cause of dementia. Although sex hormones may play a role in the etiology of AD in women, studies addressing the impact of menopausal HT on risk of AD have conflicting findings.

Finnish researchers Savolainen-Peltonen and colleagues aimed to compare postmenopausal HT use in women with and without AD. They used national drug and population registries to identify patients with AD, control women without a diagnosis of AD, and data on postmenopausal HT use.

Details of the study

In Finland, reimbursement for treatment related to AD requires cognitive testing, brain imaging, and a statement from a specialist physician. Using national records, the study investigators identified 84,739 women with a diagnosis of AD during the years 1999–2013 and the same number of control women (without AD) during the same period. A national drug reimbursement registry was used to identify HT use from the year 1994.

Findings. Women diagnosed with AD were more likely to have been current or former users of systemic HT than controls (18.6% vs 17.0%, P<.001). The odds ratios (ORs) for AD were 1.09 for the estradiol-only group and 1.17 for the estrogen-progestin group (P<.05 for both comparisons).

Initiation of HT prior to age 60 was less common among AD cases than controls (P = .006). As a continuous variable, age was not a determinant for disease risk in estradiol-only users (OR, 1.0), estrogen-progestin users (OR, 1.0), or any HT use (OR, 1.0).

The exclusive use of vaginal estrogen therapy was not associated with an elevated risk of AD (OR, 0.99).

Study strengths and limitations

This study on the association between HT and AD included a very large number of participants from a national population registry, and the use of HT was objectively determined from a controlled registry (not self-reported). In addition, AD was accurately diagnosed and differentiated from other forms of dementia.

Limitations of the study include the lack of baseline demographic data for AD risk factors for both HT users and controls. Further, an increased risk of AD may have been a cause for HT use and not a consequence, given that initial cognitive impairments may occur 7 to 8 years prior to AD diagnosis and the possibility exists that such women may have sought help for cognitive symptoms from HT. In addition, the lack of brain imaging or neurologic examination to exclude AD might also account for undiagnosed disease in controls. The authors noted that they were unable to compare the use of oral and transdermal HT preparations or the use of cyclic and continuous estrogen-progestin therapy.

EXPERT COMMENTARY

Savolainen-Peltonen H, Rahkola-Soisalo P, Hoti F, et al. Use of postmenopausal hormone therapy and risk of Alzheimer’s disease in Finland: nationwide case-control study. BMJ. 2019;364:1665.

Alzheimer disease represents the most common cause of dementia. Although sex hormones may play a role in the etiology of AD in women, studies addressing the impact of menopausal HT on risk of AD have conflicting findings.

Finnish researchers Savolainen-Peltonen and colleagues aimed to compare postmenopausal HT use in women with and without AD. They used national drug and population registries to identify patients with AD, control women without a diagnosis of AD, and data on postmenopausal HT use.

Details of the study

In Finland, reimbursement for treatment related to AD requires cognitive testing, brain imaging, and a statement from a specialist physician. Using national records, the study investigators identified 84,739 women with a diagnosis of AD during the years 1999–2013 and the same number of control women (without AD) during the same period. A national drug reimbursement registry was used to identify HT use from the year 1994.

Findings. Women diagnosed with AD were more likely to have been current or former users of systemic HT than controls (18.6% vs 17.0%, P<.001). The odds ratios (ORs) for AD were 1.09 for the estradiol-only group and 1.17 for the estrogen-progestin group (P<.05 for both comparisons).

Initiation of HT prior to age 60 was less common among AD cases than controls (P = .006). As a continuous variable, age was not a determinant for disease risk in estradiol-only users (OR, 1.0), estrogen-progestin users (OR, 1.0), or any HT use (OR, 1.0).

The exclusive use of vaginal estrogen therapy was not associated with an elevated risk of AD (OR, 0.99).

Study strengths and limitations

This study on the association between HT and AD included a very large number of participants from a national population registry, and the use of HT was objectively determined from a controlled registry (not self-reported). In addition, AD was accurately diagnosed and differentiated from other forms of dementia.

Limitations of the study include the lack of baseline demographic data for AD risk factors for both HT users and controls. Further, an increased risk of AD may have been a cause for HT use and not a consequence, given that initial cognitive impairments may occur 7 to 8 years prior to AD diagnosis and the possibility exists that such women may have sought help for cognitive symptoms from HT. In addition, the lack of brain imaging or neurologic examination to exclude AD might also account for undiagnosed disease in controls. The authors noted that they were unable to compare the use of oral and transdermal HT preparations or the use of cyclic and continuous estrogen-progestin therapy.

The first cases of HIV infection in the United States were reported in 1981. Since that time, more than 700,000 individuals in our country have died of AIDS. Slightly more than 1 million persons in the United States are currently living with HIV infection; approximately 15% of them are unaware of their infection. Men who have sex with men (MSM) and African American and Hispanic/Latino men and women are disproportionately affected by HIV infection.¹ Among men, MSM is the most common method of infection transmission, accounting for 83% of infections. Heterosexual contact accounts for 9.4% of new infections and injection drug use for 4.0%. Among women in the United States, heterosexual contact is the most common mechanism of transmission, accounting for about 87% of cases; injection drug use accounts for about 12%.¹ Perinatal transmission rates are extremely low—less than 1%—when women receive effective treatment during pregnancy and their infants are treated in the neonatal period.^1,2

The prognosis for HIV-infected patients has improved dramatically in recent years with the availability of many new and exceptionally effective highly-active antiretroviral treatment regimens. Nevertheless, the disease is not yet completely curable. Therefore, preventive measures are of great importance in reducing the enormous toll imposed by this condition.²

Evaluating effectiveness of PrEP

At the request of the US Preventive Services Task Force, Chou and colleagues recently conducted a systematic review to determine the effectiveness of pre-exposure prophylaxis (PrEP) in preventing the horizontal transmission of HIV infection.¹ The authors’ secondary objectives included assessing the relationship between degree of adherence to the prophylactic regimen and degree of effectiveness and evaluating the accuracy of various screening systems for identifying patients at high risk for acquiring HIV infection.

The authors reviewed prospective, randomized controlled trials (treatment versus no treatment or treatment versus placebo) published through 2018. Pregnant women were excluded from the studies, as were women who became pregnant after enrollment.

Two different prophylactic regimens were used in the reviewed studies: 1) the combination of tenofovir disoproxil fumarate 300 mg or 245 mg plus emtricitabine 200 mg and 2) tenofovir 300 mg alone. Most trials used the combination regimen. With the exception of one trial, the medications were given daily to uninfected patients at high risk of acquiring HIV infection. In one investigation, the administration of prophylaxis was event driven (administered after a specific high-risk exposure).

Key study findings

PrEP decreased HIV transmission in high-risk patients. Chou and colleagues found that high-risk patients included primarily MSM who did not use condoms consistently or who had a high number of sex partners, individuals in an HIV-serodiscordant relationship, and intravenous drug users who shared injection equipment.

In these high-risk patients, PrEP was associated with a significantly decreased risk of HIV transmission. Observations from 11 trials demonstrated a relative risk (RR) of 0.46 (95% confidence interval [CI], 0.33–0.66). The absolute risk reduction was -2.0% (95% CI, -2.8% to -1.2%). The duration of follow up ranged from 4 months to 4 years.

Continue to: Better medication adherence = greater prophylaxis effectiveness...

Better medication adherence = greater prophylaxis effectiveness. When adherence was ≥70%, the RR was 0.27 (95% CI, 0.19–0.39). When adherence was 40% to 70%, the RR was 0.51 (95% CI, 0.38–0.70). When adherence was ≤40%, the relative risk was 0.93 (95% CI, 0.72–1.20). Adherence was better with daily administration, as opposed to event-driven administration.

Although the combination prophylactic regimen (tenofovir plus emtricitabine) was most frequently used in the clinical trials, tenofovir alone was comparable in effectiveness.

PrEP resulted in more mild adverse effects. Patients who received PrEP were more likely to develop gastrointestinal adverse effects and renal function abnormalities when compared with patients in the control arms of the studies. These adverse effects were virtually always mild and did not necessitate discontinuation of treatment.

No increase in promiscuous sexual behavior with PrEP. Specifically, investigators did not document an increased incidence of new sexually transmitted infections (STIs) in treated patients.

PrEP did not increase adverse pregnancy outcomes. In women who became pregnant while on PrEP, and who then discontinued treatment, there was no increase in the frequency of spontaneous abortion, congenital anomalies, or other adverse pregnancy outcomes.

In addition, PrEP posed a low risk for causing drug resistance in patients who became infected despite prophylaxis. Finally, the authors found that screening instruments for identifying patients at highest risk for acquiring HIV infection had low to modest sensitivity.

My recommendations for practice

Based on the study by Chou and colleagues, and on a recent commentary by Marcus et al, I believe that the following actions are justified^1–3:

• For prophylaxis to be effective, we must identify all infected patients. Therefore, screening of asymptomatic individuals during routine health encounters is essential.
• All patients should have access to easy-to-understand information related to risk factors for HIV infection.
• Every effort should be made to promote safe sex practices, such as use of latex condoms, avoidance of sex during menses and in the presence of ulcerative genital lesions, and avoidance of use of contaminated drug-injection needles.
• All high-risk patients, as defined above, should be offered PrEP.
• To the greatest extent possible, financial barriers to PrEP should be eliminated.
• Patients receiving PrEP should be monitored for evidence of renal dysfunction. Should they become infected despite prophylaxis, they should be evaluated carefully to detect drug-resistant viral strains.
• Although PrEP is definitely effective in reducing the risk of transmission of HIV infection, it does not prevent the transmission of other STIs, such as syphilis, gonorrhea, and chlamydia.

In my practice, I administer prophyaxis on a daily basis rather than just before, or after, a high-risk exposure. This approach enhances patient adherence and, hopefully, will lead to maximum effectiveness over time. I also use the combination of tenofovir disoproxil fumarate plus emtricitabine rather than tenofovir alone because there is more published information regarding the effectiveness of the combination regimen.

The first cases of HIV infection in the United States were reported in 1981. Since that time, more than 700,000 individuals in our country have died of AIDS. Slightly more than 1 million persons in the United States are currently living with HIV infection; approximately 15% of them are unaware of their infection. Men who have sex with men (MSM) and African American and Hispanic/Latino men and women are disproportionately affected by HIV infection.¹ Among men, MSM is the most common method of infection transmission, accounting for 83% of infections. Heterosexual contact accounts for 9.4% of new infections and injection drug use for 4.0%. Among women in the United States, heterosexual contact is the most common mechanism of transmission, accounting for about 87% of cases; injection drug use accounts for about 12%.¹ Perinatal transmission rates are extremely low—less than 1%—when women receive effective treatment during pregnancy and their infants are treated in the neonatal period.^1,2

The prognosis for HIV-infected patients has improved dramatically in recent years with the availability of many new and exceptionally effective highly-active antiretroviral treatment regimens. Nevertheless, the disease is not yet completely curable. Therefore, preventive measures are of great importance in reducing the enormous toll imposed by this condition.²

Evaluating effectiveness of PrEP

At the request of the US Preventive Services Task Force, Chou and colleagues recently conducted a systematic review to determine the effectiveness of pre-exposure prophylaxis (PrEP) in preventing the horizontal transmission of HIV infection.¹ The authors’ secondary objectives included assessing the relationship between degree of adherence to the prophylactic regimen and degree of effectiveness and evaluating the accuracy of various screening systems for identifying patients at high risk for acquiring HIV infection.

The authors reviewed prospective, randomized controlled trials (treatment versus no treatment or treatment versus placebo) published through 2018. Pregnant women were excluded from the studies, as were women who became pregnant after enrollment.

Two different prophylactic regimens were used in the reviewed studies: 1) the combination of tenofovir disoproxil fumarate 300 mg or 245 mg plus emtricitabine 200 mg and 2) tenofovir 300 mg alone. Most trials used the combination regimen. With the exception of one trial, the medications were given daily to uninfected patients at high risk of acquiring HIV infection. In one investigation, the administration of prophylaxis was event driven (administered after a specific high-risk exposure).

Key study findings

PrEP decreased HIV transmission in high-risk patients. Chou and colleagues found that high-risk patients included primarily MSM who did not use condoms consistently or who had a high number of sex partners, individuals in an HIV-serodiscordant relationship, and intravenous drug users who shared injection equipment.

In these high-risk patients, PrEP was associated with a significantly decreased risk of HIV transmission. Observations from 11 trials demonstrated a relative risk (RR) of 0.46 (95% confidence interval [CI], 0.33–0.66). The absolute risk reduction was -2.0% (95% CI, -2.8% to -1.2%). The duration of follow up ranged from 4 months to 4 years.

Continue to: Better medication adherence = greater prophylaxis effectiveness...

Better medication adherence = greater prophylaxis effectiveness. When adherence was ≥70%, the RR was 0.27 (95% CI, 0.19–0.39). When adherence was 40% to 70%, the RR was 0.51 (95% CI, 0.38–0.70). When adherence was ≤40%, the relative risk was 0.93 (95% CI, 0.72–1.20). Adherence was better with daily administration, as opposed to event-driven administration.

Although the combination prophylactic regimen (tenofovir plus emtricitabine) was most frequently used in the clinical trials, tenofovir alone was comparable in effectiveness.

PrEP resulted in more mild adverse effects. Patients who received PrEP were more likely to develop gastrointestinal adverse effects and renal function abnormalities when compared with patients in the control arms of the studies. These adverse effects were virtually always mild and did not necessitate discontinuation of treatment.

No increase in promiscuous sexual behavior with PrEP. Specifically, investigators did not document an increased incidence of new sexually transmitted infections (STIs) in treated patients.

PrEP did not increase adverse pregnancy outcomes. In women who became pregnant while on PrEP, and who then discontinued treatment, there was no increase in the frequency of spontaneous abortion, congenital anomalies, or other adverse pregnancy outcomes.

In addition, PrEP posed a low risk for causing drug resistance in patients who became infected despite prophylaxis. Finally, the authors found that screening instruments for identifying patients at highest risk for acquiring HIV infection had low to modest sensitivity.

My recommendations for practice

Based on the study by Chou and colleagues, and on a recent commentary by Marcus et al, I believe that the following actions are justified^1–3:

• For prophylaxis to be effective, we must identify all infected patients. Therefore, screening of asymptomatic individuals during routine health encounters is essential.
• All patients should have access to easy-to-understand information related to risk factors for HIV infection.
• Every effort should be made to promote safe sex practices, such as use of latex condoms, avoidance of sex during menses and in the presence of ulcerative genital lesions, and avoidance of use of contaminated drug-injection needles.
• All high-risk patients, as defined above, should be offered PrEP.
• To the greatest extent possible, financial barriers to PrEP should be eliminated.
• Patients receiving PrEP should be monitored for evidence of renal dysfunction. Should they become infected despite prophylaxis, they should be evaluated carefully to detect drug-resistant viral strains.
• Although PrEP is definitely effective in reducing the risk of transmission of HIV infection, it does not prevent the transmission of other STIs, such as syphilis, gonorrhea, and chlamydia.

In my practice, I administer prophyaxis on a daily basis rather than just before, or after, a high-risk exposure. This approach enhances patient adherence and, hopefully, will lead to maximum effectiveness over time. I also use the combination of tenofovir disoproxil fumarate plus emtricitabine rather than tenofovir alone because there is more published information regarding the effectiveness of the combination regimen.

The first cases of HIV infection in the United States were reported in 1981. Since that time, more than 700,000 individuals in our country have died of AIDS. Slightly more than 1 million persons in the United States are currently living with HIV infection; approximately 15% of them are unaware of their infection. Men who have sex with men (MSM) and African American and Hispanic/Latino men and women are disproportionately affected by HIV infection.¹ Among men, MSM is the most common method of infection transmission, accounting for 83% of infections. Heterosexual contact accounts for 9.4% of new infections and injection drug use for 4.0%. Among women in the United States, heterosexual contact is the most common mechanism of transmission, accounting for about 87% of cases; injection drug use accounts for about 12%.¹ Perinatal transmission rates are extremely low—less than 1%—when women receive effective treatment during pregnancy and their infants are treated in the neonatal period.^1,2

The prognosis for HIV-infected patients has improved dramatically in recent years with the availability of many new and exceptionally effective highly-active antiretroviral treatment regimens. Nevertheless, the disease is not yet completely curable. Therefore, preventive measures are of great importance in reducing the enormous toll imposed by this condition.²

Evaluating effectiveness of PrEP

At the request of the US Preventive Services Task Force, Chou and colleagues recently conducted a systematic review to determine the effectiveness of pre-exposure prophylaxis (PrEP) in preventing the horizontal transmission of HIV infection.¹ The authors’ secondary objectives included assessing the relationship between degree of adherence to the prophylactic regimen and degree of effectiveness and evaluating the accuracy of various screening systems for identifying patients at high risk for acquiring HIV infection.

The authors reviewed prospective, randomized controlled trials (treatment versus no treatment or treatment versus placebo) published through 2018. Pregnant women were excluded from the studies, as were women who became pregnant after enrollment.

Two different prophylactic regimens were used in the reviewed studies: 1) the combination of tenofovir disoproxil fumarate 300 mg or 245 mg plus emtricitabine 200 mg and 2) tenofovir 300 mg alone. Most trials used the combination regimen. With the exception of one trial, the medications were given daily to uninfected patients at high risk of acquiring HIV infection. In one investigation, the administration of prophylaxis was event driven (administered after a specific high-risk exposure).

Key study findings

PrEP decreased HIV transmission in high-risk patients. Chou and colleagues found that high-risk patients included primarily MSM who did not use condoms consistently or who had a high number of sex partners, individuals in an HIV-serodiscordant relationship, and intravenous drug users who shared injection equipment.

In these high-risk patients, PrEP was associated with a significantly decreased risk of HIV transmission. Observations from 11 trials demonstrated a relative risk (RR) of 0.46 (95% confidence interval [CI], 0.33–0.66). The absolute risk reduction was -2.0% (95% CI, -2.8% to -1.2%). The duration of follow up ranged from 4 months to 4 years.

Continue to: Better medication adherence = greater prophylaxis effectiveness...

Better medication adherence = greater prophylaxis effectiveness. When adherence was ≥70%, the RR was 0.27 (95% CI, 0.19–0.39). When adherence was 40% to 70%, the RR was 0.51 (95% CI, 0.38–0.70). When adherence was ≤40%, the relative risk was 0.93 (95% CI, 0.72–1.20). Adherence was better with daily administration, as opposed to event-driven administration.

Although the combination prophylactic regimen (tenofovir plus emtricitabine) was most frequently used in the clinical trials, tenofovir alone was comparable in effectiveness.

PrEP resulted in more mild adverse effects. Patients who received PrEP were more likely to develop gastrointestinal adverse effects and renal function abnormalities when compared with patients in the control arms of the studies. These adverse effects were virtually always mild and did not necessitate discontinuation of treatment.

No increase in promiscuous sexual behavior with PrEP. Specifically, investigators did not document an increased incidence of new sexually transmitted infections (STIs) in treated patients.

PrEP did not increase adverse pregnancy outcomes. In women who became pregnant while on PrEP, and who then discontinued treatment, there was no increase in the frequency of spontaneous abortion, congenital anomalies, or other adverse pregnancy outcomes.

In addition, PrEP posed a low risk for causing drug resistance in patients who became infected despite prophylaxis. Finally, the authors found that screening instruments for identifying patients at highest risk for acquiring HIV infection had low to modest sensitivity.

My recommendations for practice

Based on the study by Chou and colleagues, and on a recent commentary by Marcus et al, I believe that the following actions are justified^1–3:

• For prophylaxis to be effective, we must identify all infected patients. Therefore, screening of asymptomatic individuals during routine health encounters is essential.
• All patients should have access to easy-to-understand information related to risk factors for HIV infection.
• Every effort should be made to promote safe sex practices, such as use of latex condoms, avoidance of sex during menses and in the presence of ulcerative genital lesions, and avoidance of use of contaminated drug-injection needles.
• All high-risk patients, as defined above, should be offered PrEP.
• To the greatest extent possible, financial barriers to PrEP should be eliminated.
• Patients receiving PrEP should be monitored for evidence of renal dysfunction. Should they become infected despite prophylaxis, they should be evaluated carefully to detect drug-resistant viral strains.
• Although PrEP is definitely effective in reducing the risk of transmission of HIV infection, it does not prevent the transmission of other STIs, such as syphilis, gonorrhea, and chlamydia.

In my practice, I administer prophyaxis on a daily basis rather than just before, or after, a high-risk exposure. This approach enhances patient adherence and, hopefully, will lead to maximum effectiveness over time. I also use the combination of tenofovir disoproxil fumarate plus emtricitabine rather than tenofovir alone because there is more published information regarding the effectiveness of the combination regimen.

Perinatal depression is an episode of major or minor depression that occurs during pregnancy or in the 12 months after birth; it affects about 10% of new mothers.¹ Perinatal depression adversely impacts mothers, children, and their families. Pregnant women with depression are at increased risk for preterm birth and low birth weight.² Infants of mothers with postpartum depression have reduced bonding, lower rates of breastfeeding, delayed cognitive and social development, and an increased risk of future mental health issues.³ Timely treatment of perinatal depression can improve health outcomes for the woman, her children, and their family.

Clinicians follow current screening recommendations

The American College of Obstetricians and Gynecologists (ACOG) currently recommends that ObGynsscreen all pregnant women for depression and anxiety symptoms at least once during the perinatal period.¹ Many practices use the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and postpartum. Women who screen positive are referred to mental health clinicians or have treatment initiated by their primary obstetrician.

Clinicians have been phenomenally successful in screening for perinatal depression. In a recent study from Kaiser Permanente Northern California, 98% of pregnant women were screened for perinatal depression, and a diagnosis of depression was made in 12%.⁴ Of note, only 47% of women who screened positive for depression initiated treatment, although 82% of women with the most severe symptoms initiated treatment. These data demonstrate that ObGyns consistently screen pregnant women for depression but, due to patient and system issues, treatment of all screen-positive women remains a yet unattained goal.^5,6

New USPSTF guideline: Identify women at risk for perinatal depression and refer for counseling

In 2016 the United States Preventive Services Task Force (USPSTF) recommended that pregnant and postpartum women be screened for depression with adequate systems in place to ensure diagnosis, effective treatment, and follow-up.⁷ The 2016 USPSTF recommendation was consistent with prior guidelines from both the American Academy of Pediatrics in 2010⁸ and ACOG in 2015.⁹

Now, the USPSTF is making a bold new recommendation, jumping ahead of professional societies: screen pregnant women to identify those at risk for perinatal depression and refer them for counseling (B recommendation; net benefit is moderate).^10,11 The USPSTF recommendation is based on growing literature that shows counseling women at risk for perinatal depression reduces the risk of having an episode of major depression by 40%.¹¹ Both interpersonal psychotherapy and cognitive behavioral therapy have been reported to be effective for preventing perinatal depression.^12,13

As an example of the relevant literature, in one trial performed in Rhode Island, women who were 20 to 35 weeks pregnant with a high score (≥27) on the Cooper Survey Questionnaire and on public assistance were randomized to counseling or usual care. The counseling intervention involved 4 small group (2 to 5 women) sessions of 90 minutes and one individual session of 50 minutes.¹⁴ The treatment focused on managing the transition to motherhood, developing a support system, improving communication skills to manage conflict, goal setting, and identifying psychosocial supports for new mothers. At 6 months after birth, a depressive episode had occurred in 31% of the control women and 16% of the women who had experienced the intervention (P = .041). At 12 months after birth, a depressive episode had occurred in 40% of control women and 26% of women in the intervention group (P = .052).

Of note, most cases of postpartum depression were diagnosed more than 3 months after birth, a time when new mothers generally no longer are receiving regular postpartum care by an obstetrician. The timing of the diagnosis of perinatal depression indicates that an effective handoff between the obstetrician and primary care and/or mental health clinicians is of great importance. The investigators concluded that pregnant women at very high risk for perinatal depression who receive interpersonal therapy have a lower rate of a postpartum depressive episode than women receiving usual care.¹⁴

Pregnancy, delivery, and the first year following birth are stressful for many women and their families. Women who are young, poor, and with minimal social supports are at especially high risk for developing perinatal depression. However, it will be challenging for obstetric practices to rapidly implement the new USPSTF recommendations because there is no professional consensus on how to screen women to identify those at high risk for perinatal depression, and mental health resources to care for the screen-positive women are not sufficient.

Continue to: Challenges to implementing new USPSTF guideline...

Challenges to implementing new USPSTF guideline

Challenge 1: There is no widely accepted approach for identifying women at risk for perinatal depression. The USPSTF acknowledges “there is no accurate screening tool for identifying who is at risk of perinatal depression and who might benefit from preventive interventions.”¹⁰

Obstetricians have had great success in screening for perinatal depression because validated screening tools are available. Professional societies need to reach a consensus on recommending a specific screening tool for perinatal depression risk that can be used in all obstetric practices.

Challenge 2: The USPSTF guideline identifies many risk factors for perinatal depression. The USPSTF concluded that pregnant women with one (or more) of the following risk factors are at high risk for perinatal depression and recommended that they be offered a counseling intervention:

• personal history of depression
• current depressive symptoms that do not reach a diagnostic threshold
• low income
• all adolescents
• all single mothers
• recent exposure to intimate partner violence
• elevated anxiety symptoms
• a history of significant negative life events.

For many obstetricians, most of their pregnant patients meet the USPSTF criteria for being at high risk for perinatal depression and, per the guideline, these women should have a counseling intervention.

Challenge 3: The counseling intervention recommended by the USPSTF may not be available to all women at risk for perinatal depression. The USPSTF literature review, including a meta-analysis of 49 randomized clinical trials, concluded that for women at risk for perinatal depression, a counseling intervention reduces the risk of depression. In the published literature, many counseling interventions to reduce the risk of perinatal depression involve 6 to 12 hours of contact time over 4 to 8 episodes.

For many health systems, the resources available to provide mental health services are very limited. If most pregnant women need a counseling intervention, the health system must evolve to meet this need. In addition, risk factors for perinatal depression are also risk factors for having difficulty in participating in mental health interventions due to limitations, such as lack of transportation, social support, and money.⁴

Fortunately, clinicians from many backgrounds, including psychologists, social workers, nurse practitioners, and public health workers have the experience and/or training to provide the counseling interventions that have been shown to reduce the risk of perinatal depression. Health systems will need to tap all these resources to accommodate the large numbers of pregnant women who will be referred for counseling interventions. Pilot projects using electronic interventions, including telephone counseling, smartphone apps, and internet programs show promise.^15,16 Electronic interventions have the potential to reach many pregnant women without over-taxing limited mental health resources.

A practical approach

Identify women at the greatest risk for perinatal depression and focus counseling interventions on this group. In my opinion, implementation of the USPSTF recommendation will take time. A practical approach would be to implement them in a staged sequence, focusing first on the women at highest risk, later extending the program to women at lesser risk. The two factors that confer the greatest risk of perinatal depression are a personal history of depression and high depression symptoms that do not meet criteria for depression.¹⁷ Many women with depression who take antidepressants discontinue their medications during pregnancy. These women are at very high risk for perinatal depression and deserve extra attention.¹⁸

Continue to: To identify women with a prior personal history of depression...

To identify women with a prior personal history of depression, it may be helpful to ask open-ended questions about a past diagnosis of depression or a mood disorder or use of antidepressant medications. To identify women with the greatest depression symptoms, utilize a lower cut-off for screening positive in the Edinburgh questionnaire. Practices that use an EPDS screen-positive score of 13 or greater could reduce the cut-off to 10 or 11, which would increase the number of women referred for evaluation and treatment.¹⁹

Clinical judgment and screening

Screening for prevalent depression and screening for women at increased risk for perinatal depression is challenging. ACOG highlights two important clinical issues¹:

“Women with current depression or anxiety, a history of perinatal mood disorders, risk factors for perinatal mood disorders or suicidal thoughts warrant particularly close monitoring, evaluation and assessment.”

When screening for perinatal depression, screening test results should be interpreted within the clinical context. “A normal score for a tearful patient with a flat affect does not exclude depression; an elevated score in the context of an acute stressful event may resolve with close follow-up.”

In addition, women who screen-positive for prevalent depression and are subsequently evaluated by a mental health specialist may be identified as having mental health problems such as an anxiety disorder, substance misuse, or borderline personality disorder.²⁰

Policy changes that support pregnant women and mothers could help to reduce the stress of pregnancy, birth, and childrearing, thereby reducing the risk of perinatal depression. The United States stands alone among rich nations in not providing paid parental leave. Paid maternity and parental leave would help many families respond more effectively to the initial stresses of parenthood.²¹ For women and families living in poverty, improved social support, including secure housing, protection from abusive partners, transportation resources, and access to healthy foods likely will reduce both stress and the risk of depression.

The ultimate goal: A healthy pregnancy

Clinicians have been phenomenally successful in screening for perinatal depression. The new USPSTF recommendation adds the prevention of perinatal depression to the goals of a healthy pregnancy. This recommendation builds upon the foundation of screening for acute illness (depression), pivoting to the public health perspective of disease prevention.

Perinatal depression is an episode of major or minor depression that occurs during pregnancy or in the 12 months after birth; it affects about 10% of new mothers.¹ Perinatal depression adversely impacts mothers, children, and their families. Pregnant women with depression are at increased risk for preterm birth and low birth weight.² Infants of mothers with postpartum depression have reduced bonding, lower rates of breastfeeding, delayed cognitive and social development, and an increased risk of future mental health issues.³ Timely treatment of perinatal depression can improve health outcomes for the woman, her children, and their family.

Clinicians follow current screening recommendations

The American College of Obstetricians and Gynecologists (ACOG) currently recommends that ObGynsscreen all pregnant women for depression and anxiety symptoms at least once during the perinatal period.¹ Many practices use the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and postpartum. Women who screen positive are referred to mental health clinicians or have treatment initiated by their primary obstetrician.

Clinicians have been phenomenally successful in screening for perinatal depression. In a recent study from Kaiser Permanente Northern California, 98% of pregnant women were screened for perinatal depression, and a diagnosis of depression was made in 12%.⁴ Of note, only 47% of women who screened positive for depression initiated treatment, although 82% of women with the most severe symptoms initiated treatment. These data demonstrate that ObGyns consistently screen pregnant women for depression but, due to patient and system issues, treatment of all screen-positive women remains a yet unattained goal.^5,6

New USPSTF guideline: Identify women at risk for perinatal depression and refer for counseling

In 2016 the United States Preventive Services Task Force (USPSTF) recommended that pregnant and postpartum women be screened for depression with adequate systems in place to ensure diagnosis, effective treatment, and follow-up.⁷ The 2016 USPSTF recommendation was consistent with prior guidelines from both the American Academy of Pediatrics in 2010⁸ and ACOG in 2015.⁹

Now, the USPSTF is making a bold new recommendation, jumping ahead of professional societies: screen pregnant women to identify those at risk for perinatal depression and refer them for counseling (B recommendation; net benefit is moderate).^10,11 The USPSTF recommendation is based on growing literature that shows counseling women at risk for perinatal depression reduces the risk of having an episode of major depression by 40%.¹¹ Both interpersonal psychotherapy and cognitive behavioral therapy have been reported to be effective for preventing perinatal depression.^12,13

As an example of the relevant literature, in one trial performed in Rhode Island, women who were 20 to 35 weeks pregnant with a high score (≥27) on the Cooper Survey Questionnaire and on public assistance were randomized to counseling or usual care. The counseling intervention involved 4 small group (2 to 5 women) sessions of 90 minutes and one individual session of 50 minutes.¹⁴ The treatment focused on managing the transition to motherhood, developing a support system, improving communication skills to manage conflict, goal setting, and identifying psychosocial supports for new mothers. At 6 months after birth, a depressive episode had occurred in 31% of the control women and 16% of the women who had experienced the intervention (P = .041). At 12 months after birth, a depressive episode had occurred in 40% of control women and 26% of women in the intervention group (P = .052).

Of note, most cases of postpartum depression were diagnosed more than 3 months after birth, a time when new mothers generally no longer are receiving regular postpartum care by an obstetrician. The timing of the diagnosis of perinatal depression indicates that an effective handoff between the obstetrician and primary care and/or mental health clinicians is of great importance. The investigators concluded that pregnant women at very high risk for perinatal depression who receive interpersonal therapy have a lower rate of a postpartum depressive episode than women receiving usual care.¹⁴

Pregnancy, delivery, and the first year following birth are stressful for many women and their families. Women who are young, poor, and with minimal social supports are at especially high risk for developing perinatal depression. However, it will be challenging for obstetric practices to rapidly implement the new USPSTF recommendations because there is no professional consensus on how to screen women to identify those at high risk for perinatal depression, and mental health resources to care for the screen-positive women are not sufficient.

Continue to: Challenges to implementing new USPSTF guideline...

Challenges to implementing new USPSTF guideline

Challenge 1: There is no widely accepted approach for identifying women at risk for perinatal depression. The USPSTF acknowledges “there is no accurate screening tool for identifying who is at risk of perinatal depression and who might benefit from preventive interventions.”¹⁰

Obstetricians have had great success in screening for perinatal depression because validated screening tools are available. Professional societies need to reach a consensus on recommending a specific screening tool for perinatal depression risk that can be used in all obstetric practices.

Challenge 2: The USPSTF guideline identifies many risk factors for perinatal depression. The USPSTF concluded that pregnant women with one (or more) of the following risk factors are at high risk for perinatal depression and recommended that they be offered a counseling intervention:

• personal history of depression
• current depressive symptoms that do not reach a diagnostic threshold
• low income
• all adolescents
• all single mothers
• recent exposure to intimate partner violence
• elevated anxiety symptoms
• a history of significant negative life events.

For many obstetricians, most of their pregnant patients meet the USPSTF criteria for being at high risk for perinatal depression and, per the guideline, these women should have a counseling intervention.

Challenge 3: The counseling intervention recommended by the USPSTF may not be available to all women at risk for perinatal depression. The USPSTF literature review, including a meta-analysis of 49 randomized clinical trials, concluded that for women at risk for perinatal depression, a counseling intervention reduces the risk of depression. In the published literature, many counseling interventions to reduce the risk of perinatal depression involve 6 to 12 hours of contact time over 4 to 8 episodes.

For many health systems, the resources available to provide mental health services are very limited. If most pregnant women need a counseling intervention, the health system must evolve to meet this need. In addition, risk factors for perinatal depression are also risk factors for having difficulty in participating in mental health interventions due to limitations, such as lack of transportation, social support, and money.⁴

Fortunately, clinicians from many backgrounds, including psychologists, social workers, nurse practitioners, and public health workers have the experience and/or training to provide the counseling interventions that have been shown to reduce the risk of perinatal depression. Health systems will need to tap all these resources to accommodate the large numbers of pregnant women who will be referred for counseling interventions. Pilot projects using electronic interventions, including telephone counseling, smartphone apps, and internet programs show promise.^15,16 Electronic interventions have the potential to reach many pregnant women without over-taxing limited mental health resources.

A practical approach

Identify women at the greatest risk for perinatal depression and focus counseling interventions on this group. In my opinion, implementation of the USPSTF recommendation will take time. A practical approach would be to implement them in a staged sequence, focusing first on the women at highest risk, later extending the program to women at lesser risk. The two factors that confer the greatest risk of perinatal depression are a personal history of depression and high depression symptoms that do not meet criteria for depression.¹⁷ Many women with depression who take antidepressants discontinue their medications during pregnancy. These women are at very high risk for perinatal depression and deserve extra attention.¹⁸

Continue to: To identify women with a prior personal history of depression...

To identify women with a prior personal history of depression, it may be helpful to ask open-ended questions about a past diagnosis of depression or a mood disorder or use of antidepressant medications. To identify women with the greatest depression symptoms, utilize a lower cut-off for screening positive in the Edinburgh questionnaire. Practices that use an EPDS screen-positive score of 13 or greater could reduce the cut-off to 10 or 11, which would increase the number of women referred for evaluation and treatment.¹⁹

Clinical judgment and screening

Screening for prevalent depression and screening for women at increased risk for perinatal depression is challenging. ACOG highlights two important clinical issues¹:

“Women with current depression or anxiety, a history of perinatal mood disorders, risk factors for perinatal mood disorders or suicidal thoughts warrant particularly close monitoring, evaluation and assessment.”

When screening for perinatal depression, screening test results should be interpreted within the clinical context. “A normal score for a tearful patient with a flat affect does not exclude depression; an elevated score in the context of an acute stressful event may resolve with close follow-up.”

In addition, women who screen-positive for prevalent depression and are subsequently evaluated by a mental health specialist may be identified as having mental health problems such as an anxiety disorder, substance misuse, or borderline personality disorder.²⁰

Policy changes that support pregnant women and mothers could help to reduce the stress of pregnancy, birth, and childrearing, thereby reducing the risk of perinatal depression. The United States stands alone among rich nations in not providing paid parental leave. Paid maternity and parental leave would help many families respond more effectively to the initial stresses of parenthood.²¹ For women and families living in poverty, improved social support, including secure housing, protection from abusive partners, transportation resources, and access to healthy foods likely will reduce both stress and the risk of depression.

The ultimate goal: A healthy pregnancy

Clinicians have been phenomenally successful in screening for perinatal depression. The new USPSTF recommendation adds the prevention of perinatal depression to the goals of a healthy pregnancy. This recommendation builds upon the foundation of screening for acute illness (depression), pivoting to the public health perspective of disease prevention.

Perinatal depression is an episode of major or minor depression that occurs during pregnancy or in the 12 months after birth; it affects about 10% of new mothers.¹ Perinatal depression adversely impacts mothers, children, and their families. Pregnant women with depression are at increased risk for preterm birth and low birth weight.² Infants of mothers with postpartum depression have reduced bonding, lower rates of breastfeeding, delayed cognitive and social development, and an increased risk of future mental health issues.³ Timely treatment of perinatal depression can improve health outcomes for the woman, her children, and their family.

Clinicians follow current screening recommendations

The American College of Obstetricians and Gynecologists (ACOG) currently recommends that ObGynsscreen all pregnant women for depression and anxiety symptoms at least once during the perinatal period.¹ Many practices use the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and postpartum. Women who screen positive are referred to mental health clinicians or have treatment initiated by their primary obstetrician.

Clinicians have been phenomenally successful in screening for perinatal depression. In a recent study from Kaiser Permanente Northern California, 98% of pregnant women were screened for perinatal depression, and a diagnosis of depression was made in 12%.⁴ Of note, only 47% of women who screened positive for depression initiated treatment, although 82% of women with the most severe symptoms initiated treatment. These data demonstrate that ObGyns consistently screen pregnant women for depression but, due to patient and system issues, treatment of all screen-positive women remains a yet unattained goal.^5,6

New USPSTF guideline: Identify women at risk for perinatal depression and refer for counseling

In 2016 the United States Preventive Services Task Force (USPSTF) recommended that pregnant and postpartum women be screened for depression with adequate systems in place to ensure diagnosis, effective treatment, and follow-up.⁷ The 2016 USPSTF recommendation was consistent with prior guidelines from both the American Academy of Pediatrics in 2010⁸ and ACOG in 2015.⁹

Now, the USPSTF is making a bold new recommendation, jumping ahead of professional societies: screen pregnant women to identify those at risk for perinatal depression and refer them for counseling (B recommendation; net benefit is moderate).^10,11 The USPSTF recommendation is based on growing literature that shows counseling women at risk for perinatal depression reduces the risk of having an episode of major depression by 40%.¹¹ Both interpersonal psychotherapy and cognitive behavioral therapy have been reported to be effective for preventing perinatal depression.^12,13

As an example of the relevant literature, in one trial performed in Rhode Island, women who were 20 to 35 weeks pregnant with a high score (≥27) on the Cooper Survey Questionnaire and on public assistance were randomized to counseling or usual care. The counseling intervention involved 4 small group (2 to 5 women) sessions of 90 minutes and one individual session of 50 minutes.¹⁴ The treatment focused on managing the transition to motherhood, developing a support system, improving communication skills to manage conflict, goal setting, and identifying psychosocial supports for new mothers. At 6 months after birth, a depressive episode had occurred in 31% of the control women and 16% of the women who had experienced the intervention (P = .041). At 12 months after birth, a depressive episode had occurred in 40% of control women and 26% of women in the intervention group (P = .052).

Of note, most cases of postpartum depression were diagnosed more than 3 months after birth, a time when new mothers generally no longer are receiving regular postpartum care by an obstetrician. The timing of the diagnosis of perinatal depression indicates that an effective handoff between the obstetrician and primary care and/or mental health clinicians is of great importance. The investigators concluded that pregnant women at very high risk for perinatal depression who receive interpersonal therapy have a lower rate of a postpartum depressive episode than women receiving usual care.¹⁴

Pregnancy, delivery, and the first year following birth are stressful for many women and their families. Women who are young, poor, and with minimal social supports are at especially high risk for developing perinatal depression. However, it will be challenging for obstetric practices to rapidly implement the new USPSTF recommendations because there is no professional consensus on how to screen women to identify those at high risk for perinatal depression, and mental health resources to care for the screen-positive women are not sufficient.

Continue to: Challenges to implementing new USPSTF guideline...

Challenges to implementing new USPSTF guideline

Challenge 1: There is no widely accepted approach for identifying women at risk for perinatal depression. The USPSTF acknowledges “there is no accurate screening tool for identifying who is at risk of perinatal depression and who might benefit from preventive interventions.”¹⁰

Obstetricians have had great success in screening for perinatal depression because validated screening tools are available. Professional societies need to reach a consensus on recommending a specific screening tool for perinatal depression risk that can be used in all obstetric practices.

Challenge 2: The USPSTF guideline identifies many risk factors for perinatal depression. The USPSTF concluded that pregnant women with one (or more) of the following risk factors are at high risk for perinatal depression and recommended that they be offered a counseling intervention:

• personal history of depression
• current depressive symptoms that do not reach a diagnostic threshold
• low income
• all adolescents
• all single mothers
• recent exposure to intimate partner violence
• elevated anxiety symptoms
• a history of significant negative life events.

For many obstetricians, most of their pregnant patients meet the USPSTF criteria for being at high risk for perinatal depression and, per the guideline, these women should have a counseling intervention.

Challenge 3: The counseling intervention recommended by the USPSTF may not be available to all women at risk for perinatal depression. The USPSTF literature review, including a meta-analysis of 49 randomized clinical trials, concluded that for women at risk for perinatal depression, a counseling intervention reduces the risk of depression. In the published literature, many counseling interventions to reduce the risk of perinatal depression involve 6 to 12 hours of contact time over 4 to 8 episodes.

For many health systems, the resources available to provide mental health services are very limited. If most pregnant women need a counseling intervention, the health system must evolve to meet this need. In addition, risk factors for perinatal depression are also risk factors for having difficulty in participating in mental health interventions due to limitations, such as lack of transportation, social support, and money.⁴

Fortunately, clinicians from many backgrounds, including psychologists, social workers, nurse practitioners, and public health workers have the experience and/or training to provide the counseling interventions that have been shown to reduce the risk of perinatal depression. Health systems will need to tap all these resources to accommodate the large numbers of pregnant women who will be referred for counseling interventions. Pilot projects using electronic interventions, including telephone counseling, smartphone apps, and internet programs show promise.^15,16 Electronic interventions have the potential to reach many pregnant women without over-taxing limited mental health resources.

A practical approach

Identify women at the greatest risk for perinatal depression and focus counseling interventions on this group. In my opinion, implementation of the USPSTF recommendation will take time. A practical approach would be to implement them in a staged sequence, focusing first on the women at highest risk, later extending the program to women at lesser risk. The two factors that confer the greatest risk of perinatal depression are a personal history of depression and high depression symptoms that do not meet criteria for depression.¹⁷ Many women with depression who take antidepressants discontinue their medications during pregnancy. These women are at very high risk for perinatal depression and deserve extra attention.¹⁸

Continue to: To identify women with a prior personal history of depression...

To identify women with a prior personal history of depression, it may be helpful to ask open-ended questions about a past diagnosis of depression or a mood disorder or use of antidepressant medications. To identify women with the greatest depression symptoms, utilize a lower cut-off for screening positive in the Edinburgh questionnaire. Practices that use an EPDS screen-positive score of 13 or greater could reduce the cut-off to 10 or 11, which would increase the number of women referred for evaluation and treatment.¹⁹

Clinical judgment and screening

Screening for prevalent depression and screening for women at increased risk for perinatal depression is challenging. ACOG highlights two important clinical issues¹:

“Women with current depression or anxiety, a history of perinatal mood disorders, risk factors for perinatal mood disorders or suicidal thoughts warrant particularly close monitoring, evaluation and assessment.”

When screening for perinatal depression, screening test results should be interpreted within the clinical context. “A normal score for a tearful patient with a flat affect does not exclude depression; an elevated score in the context of an acute stressful event may resolve with close follow-up.”

In addition, women who screen-positive for prevalent depression and are subsequently evaluated by a mental health specialist may be identified as having mental health problems such as an anxiety disorder, substance misuse, or borderline personality disorder.²⁰

Policy changes that support pregnant women and mothers could help to reduce the stress of pregnancy, birth, and childrearing, thereby reducing the risk of perinatal depression. The United States stands alone among rich nations in not providing paid parental leave. Paid maternity and parental leave would help many families respond more effectively to the initial stresses of parenthood.²¹ For women and families living in poverty, improved social support, including secure housing, protection from abusive partners, transportation resources, and access to healthy foods likely will reduce both stress and the risk of depression.

The ultimate goal: A healthy pregnancy

Clinicians have been phenomenally successful in screening for perinatal depression. The new USPSTF recommendation adds the prevention of perinatal depression to the goals of a healthy pregnancy. This recommendation builds upon the foundation of screening for acute illness (depression), pivoting to the public health perspective of disease prevention.