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Hope for targeted management of preeclampsia
In medicine, there are many diseases and conditions that pose significant challenges to health care practitioners. For example, within brain science, there are patients with debilitating neurodegenerative diseases; within emergency medicine, there are patients who have suffered severe and acute trauma; within pediatrics, there are patients with terminal illnesses, such as cancer. In ob.gyn., one of the great obstetrical syndromes is preeclampsia.
Humans have known about preeclampsia for thousands of years, dating back to the 4th and 5th centuries B.C., since the time of Hippocrates. Ancient writings on medical conditions of women reflect a recognition of preeclampsia and eclampsia, although formal classification of the condition as a hypertensive disorder associated specifically with pregnancy did not occur until the late 1800s. Despite this, the pathology of preeclampsia is significantly underdefined, and because the underlying causes of preeclampsia are largely unknown, prevention and management continue to be hindered.
However, recent research indicating an association between statin use and prevention of preeclampsia has given us some hope that targeted management is possible. As ob.gyns. continue to grapple with the intricacies of managing patients with preeclampsia, a condition we increasingly see because of concurrent rises in being overweight, being obese, and having diabetes during pregnancy, so we are eager to see whether the research might confirm an effective role for statins in patient care. Although statins are still quite far from becoming a new standard of care, we are, as a specialty, hungry for a solution to this millennia-old problem.
Therefore, this month we have invited Maged Costantine, MD, an associate professor in the department of obstetrics and gynecology and division of maternal fetal medicine at the University of Texas Medical Branch in Galveston, to discuss this novel and exciting new area of research.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
In medicine, there are many diseases and conditions that pose significant challenges to health care practitioners. For example, within brain science, there are patients with debilitating neurodegenerative diseases; within emergency medicine, there are patients who have suffered severe and acute trauma; within pediatrics, there are patients with terminal illnesses, such as cancer. In ob.gyn., one of the great obstetrical syndromes is preeclampsia.
Humans have known about preeclampsia for thousands of years, dating back to the 4th and 5th centuries B.C., since the time of Hippocrates. Ancient writings on medical conditions of women reflect a recognition of preeclampsia and eclampsia, although formal classification of the condition as a hypertensive disorder associated specifically with pregnancy did not occur until the late 1800s. Despite this, the pathology of preeclampsia is significantly underdefined, and because the underlying causes of preeclampsia are largely unknown, prevention and management continue to be hindered.
However, recent research indicating an association between statin use and prevention of preeclampsia has given us some hope that targeted management is possible. As ob.gyns. continue to grapple with the intricacies of managing patients with preeclampsia, a condition we increasingly see because of concurrent rises in being overweight, being obese, and having diabetes during pregnancy, so we are eager to see whether the research might confirm an effective role for statins in patient care. Although statins are still quite far from becoming a new standard of care, we are, as a specialty, hungry for a solution to this millennia-old problem.
Therefore, this month we have invited Maged Costantine, MD, an associate professor in the department of obstetrics and gynecology and division of maternal fetal medicine at the University of Texas Medical Branch in Galveston, to discuss this novel and exciting new area of research.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
In medicine, there are many diseases and conditions that pose significant challenges to health care practitioners. For example, within brain science, there are patients with debilitating neurodegenerative diseases; within emergency medicine, there are patients who have suffered severe and acute trauma; within pediatrics, there are patients with terminal illnesses, such as cancer. In ob.gyn., one of the great obstetrical syndromes is preeclampsia.
Humans have known about preeclampsia for thousands of years, dating back to the 4th and 5th centuries B.C., since the time of Hippocrates. Ancient writings on medical conditions of women reflect a recognition of preeclampsia and eclampsia, although formal classification of the condition as a hypertensive disorder associated specifically with pregnancy did not occur until the late 1800s. Despite this, the pathology of preeclampsia is significantly underdefined, and because the underlying causes of preeclampsia are largely unknown, prevention and management continue to be hindered.
However, recent research indicating an association between statin use and prevention of preeclampsia has given us some hope that targeted management is possible. As ob.gyns. continue to grapple with the intricacies of managing patients with preeclampsia, a condition we increasingly see because of concurrent rises in being overweight, being obese, and having diabetes during pregnancy, so we are eager to see whether the research might confirm an effective role for statins in patient care. Although statins are still quite far from becoming a new standard of care, we are, as a specialty, hungry for a solution to this millennia-old problem.
Therefore, this month we have invited Maged Costantine, MD, an associate professor in the department of obstetrics and gynecology and division of maternal fetal medicine at the University of Texas Medical Branch in Galveston, to discuss this novel and exciting new area of research.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Multidisciplinary teams offer key to complex deliveries
Medical practice has evolved, and will continue to do so, as we begin pushing for more personalized and better precision health care. Gone are the days of the general practitioner who attempted to treat all conditions in all patients. Health care is now so complex that not only specialists but also so-called superspecialists are needed to manage complicated cases successfully.
One of the biggest challenges, and greatest opportunities, in ob.gyn. is the need to establish a multidisciplinary health team to the address the needs of today’s patients. More than ever, we are working with patients with advanced maternal age having their first pregnancies. More than ever, we are managing patients who have preexisting diabetes and are concurrently overweight or obese. More than ever, our patients are having multiple cesarean deliveries. More than ever, our patients are hoping – perhaps even expecting – to retain their fertility after a complicated delivery. More than ever, a single patient may need the guidance and care of not just an ob.gyn. or maternal-fetal medicine subspecialist but also an endocrinologist, cardiologist, diabetologist, genetic counselor, nutritionist – the list could go on.
The emergence and continued growth of personalized and preventive medicine in the very near future will catalyze fundamental changes at many different levels in health care and health systems. The need to establish multidisciplinary care teams is already apparent in ob.gyn. but is especially necessary in helping patients who experience complicated deliveries that could jeopardize their immediate and long-term health and fertility.
This month, we have invited M. Ozhan Turan, MD, PhD, the director of fetal therapy and complex obstetric surgery at the University of Maryland, Baltimore, to discuss the use of a multidisciplinary team in the management of patients with placenta accreta and other forms of morbidly adherent placenta.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column.
Medical practice has evolved, and will continue to do so, as we begin pushing for more personalized and better precision health care. Gone are the days of the general practitioner who attempted to treat all conditions in all patients. Health care is now so complex that not only specialists but also so-called superspecialists are needed to manage complicated cases successfully.
One of the biggest challenges, and greatest opportunities, in ob.gyn. is the need to establish a multidisciplinary health team to the address the needs of today’s patients. More than ever, we are working with patients with advanced maternal age having their first pregnancies. More than ever, we are managing patients who have preexisting diabetes and are concurrently overweight or obese. More than ever, our patients are having multiple cesarean deliveries. More than ever, our patients are hoping – perhaps even expecting – to retain their fertility after a complicated delivery. More than ever, a single patient may need the guidance and care of not just an ob.gyn. or maternal-fetal medicine subspecialist but also an endocrinologist, cardiologist, diabetologist, genetic counselor, nutritionist – the list could go on.
The emergence and continued growth of personalized and preventive medicine in the very near future will catalyze fundamental changes at many different levels in health care and health systems. The need to establish multidisciplinary care teams is already apparent in ob.gyn. but is especially necessary in helping patients who experience complicated deliveries that could jeopardize their immediate and long-term health and fertility.
This month, we have invited M. Ozhan Turan, MD, PhD, the director of fetal therapy and complex obstetric surgery at the University of Maryland, Baltimore, to discuss the use of a multidisciplinary team in the management of patients with placenta accreta and other forms of morbidly adherent placenta.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column.
Medical practice has evolved, and will continue to do so, as we begin pushing for more personalized and better precision health care. Gone are the days of the general practitioner who attempted to treat all conditions in all patients. Health care is now so complex that not only specialists but also so-called superspecialists are needed to manage complicated cases successfully.
One of the biggest challenges, and greatest opportunities, in ob.gyn. is the need to establish a multidisciplinary health team to the address the needs of today’s patients. More than ever, we are working with patients with advanced maternal age having their first pregnancies. More than ever, we are managing patients who have preexisting diabetes and are concurrently overweight or obese. More than ever, our patients are having multiple cesarean deliveries. More than ever, our patients are hoping – perhaps even expecting – to retain their fertility after a complicated delivery. More than ever, a single patient may need the guidance and care of not just an ob.gyn. or maternal-fetal medicine subspecialist but also an endocrinologist, cardiologist, diabetologist, genetic counselor, nutritionist – the list could go on.
The emergence and continued growth of personalized and preventive medicine in the very near future will catalyze fundamental changes at many different levels in health care and health systems. The need to establish multidisciplinary care teams is already apparent in ob.gyn. but is especially necessary in helping patients who experience complicated deliveries that could jeopardize their immediate and long-term health and fertility.
This month, we have invited M. Ozhan Turan, MD, PhD, the director of fetal therapy and complex obstetric surgery at the University of Maryland, Baltimore, to discuss the use of a multidisciplinary team in the management of patients with placenta accreta and other forms of morbidly adherent placenta.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column.
The moving target of gestational diabetes care
With the rise of obesity and diabetes, especially type 2 diabetes, in the general population, the likelihood of encountering a patient with diabetes in pregnancy also continues to increase. Women with diabetes who are pregnant require specialized medical guidance, additional monitoring, and a health care team well versed in the possible complications that can arise during pregnancy, delivery, and after birth.
Even with strict glycemic control, women with diabetes in pregnancy are much more likely to experience complications, such as preeclampsia, babies with major congenital defects, large-for-gestational-age fetuses, and children with a higher propensity for chronic diseases later in life, compared with women without diabetes.
Therefore, it has been an incredible honor for me to have taken part in the work of the Diabetes in Pregnancy Study Group of North America (DPSG-NA) for the last 20 years. The DPSG-NA meetings have served as a forum for the dissemination of data, gathered through collaboration between researchers and clinical care teams in the United States and abroad. This year, the DPSG-NA will meet in Washington, D.C., Oct. 26-28, to discuss a range of topics under the theme of managing and preventing diabetes and obesity in pregnancy.
I am delighted that one of the speakers at the DPSG-NA meeting is this month’s Master Class guest author, Lynn Yee, MD, assistant professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine, Chicago. Dr. Yee will address the need to reduce disparities in the quality and availability of care for patients with diabetes in pregnancy, an extension of the June Master Class column that discussed the critical role that ob.gyns. can play in improving health equity for all patients.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
With the rise of obesity and diabetes, especially type 2 diabetes, in the general population, the likelihood of encountering a patient with diabetes in pregnancy also continues to increase. Women with diabetes who are pregnant require specialized medical guidance, additional monitoring, and a health care team well versed in the possible complications that can arise during pregnancy, delivery, and after birth.
Even with strict glycemic control, women with diabetes in pregnancy are much more likely to experience complications, such as preeclampsia, babies with major congenital defects, large-for-gestational-age fetuses, and children with a higher propensity for chronic diseases later in life, compared with women without diabetes.
Therefore, it has been an incredible honor for me to have taken part in the work of the Diabetes in Pregnancy Study Group of North America (DPSG-NA) for the last 20 years. The DPSG-NA meetings have served as a forum for the dissemination of data, gathered through collaboration between researchers and clinical care teams in the United States and abroad. This year, the DPSG-NA will meet in Washington, D.C., Oct. 26-28, to discuss a range of topics under the theme of managing and preventing diabetes and obesity in pregnancy.
I am delighted that one of the speakers at the DPSG-NA meeting is this month’s Master Class guest author, Lynn Yee, MD, assistant professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine, Chicago. Dr. Yee will address the need to reduce disparities in the quality and availability of care for patients with diabetes in pregnancy, an extension of the June Master Class column that discussed the critical role that ob.gyns. can play in improving health equity for all patients.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
With the rise of obesity and diabetes, especially type 2 diabetes, in the general population, the likelihood of encountering a patient with diabetes in pregnancy also continues to increase. Women with diabetes who are pregnant require specialized medical guidance, additional monitoring, and a health care team well versed in the possible complications that can arise during pregnancy, delivery, and after birth.
Even with strict glycemic control, women with diabetes in pregnancy are much more likely to experience complications, such as preeclampsia, babies with major congenital defects, large-for-gestational-age fetuses, and children with a higher propensity for chronic diseases later in life, compared with women without diabetes.
Therefore, it has been an incredible honor for me to have taken part in the work of the Diabetes in Pregnancy Study Group of North America (DPSG-NA) for the last 20 years. The DPSG-NA meetings have served as a forum for the dissemination of data, gathered through collaboration between researchers and clinical care teams in the United States and abroad. This year, the DPSG-NA will meet in Washington, D.C., Oct. 26-28, to discuss a range of topics under the theme of managing and preventing diabetes and obesity in pregnancy.
I am delighted that one of the speakers at the DPSG-NA meeting is this month’s Master Class guest author, Lynn Yee, MD, assistant professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine, Chicago. Dr. Yee will address the need to reduce disparities in the quality and availability of care for patients with diabetes in pregnancy, an extension of the June Master Class column that discussed the critical role that ob.gyns. can play in improving health equity for all patients.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Health inequities take a societal toll
Arguably one of the most important public health issues in our nation is the gap between high-quality care and the people who need it most. The passage of the Affordable Care Act was meant, in part, to reduce this gap and increase health equity in terms of both eligibility for, and access to, care. However, lower-income residents, especially those from minority groups, are more likely to be hospitalized for asthma, hypertension, heart disease, and diabetes, and to experience infertility, preterm birth, and fetal death.
Health disparities, or inequities, translate not only into greater suffering for certain segments of the population, but also to significantly greater health care costs for everyone. Racial health disparities are associated with an estimated $35 billion annually in excess expenditures, $10 billion in lost productivity, and nearly $200 billion in premature deaths, according to an article in the Harvard Business Review. A 2013 study estimated that reducing racial disparities in adverse pregnancy outcomes – preeclampsia, preterm birth, gestational diabetes mellitus, and fetal death/stillbirth – could generate health care cost savings of up to $214 million per year (Matern Child Health J. 2013 Oct;17[8]:1518-25).
Several years ago, the State of Maryland took a unique approach to reducing health disparities by passing the Maryland Health Improvement and Disparities Reduction Act. One of the major components of this legislation was the creation of Health Enterprise Zones (HEZs), distinct geographical areas across the state dedicated to addressing health disparities and improving access to high-quality care. This incentive-based program provides state-funded resources to primary care providers and community-based health organizations specifically to help the neighborhoods they serve. I was deeply honored to serve as chairman of the task force that recommended the establishment of the HEZs.
For this Master Class, I have invited Melissa A. Simon, MD, the George H. Gardner, MD, Professor of Clinical Gynecology and professor of obstetrics and gynecology at Northwestern University, Chicago, to provide some practical advice on how to create greater health equity.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Arguably one of the most important public health issues in our nation is the gap between high-quality care and the people who need it most. The passage of the Affordable Care Act was meant, in part, to reduce this gap and increase health equity in terms of both eligibility for, and access to, care. However, lower-income residents, especially those from minority groups, are more likely to be hospitalized for asthma, hypertension, heart disease, and diabetes, and to experience infertility, preterm birth, and fetal death.
Health disparities, or inequities, translate not only into greater suffering for certain segments of the population, but also to significantly greater health care costs for everyone. Racial health disparities are associated with an estimated $35 billion annually in excess expenditures, $10 billion in lost productivity, and nearly $200 billion in premature deaths, according to an article in the Harvard Business Review. A 2013 study estimated that reducing racial disparities in adverse pregnancy outcomes – preeclampsia, preterm birth, gestational diabetes mellitus, and fetal death/stillbirth – could generate health care cost savings of up to $214 million per year (Matern Child Health J. 2013 Oct;17[8]:1518-25).
Several years ago, the State of Maryland took a unique approach to reducing health disparities by passing the Maryland Health Improvement and Disparities Reduction Act. One of the major components of this legislation was the creation of Health Enterprise Zones (HEZs), distinct geographical areas across the state dedicated to addressing health disparities and improving access to high-quality care. This incentive-based program provides state-funded resources to primary care providers and community-based health organizations specifically to help the neighborhoods they serve. I was deeply honored to serve as chairman of the task force that recommended the establishment of the HEZs.
For this Master Class, I have invited Melissa A. Simon, MD, the George H. Gardner, MD, Professor of Clinical Gynecology and professor of obstetrics and gynecology at Northwestern University, Chicago, to provide some practical advice on how to create greater health equity.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Arguably one of the most important public health issues in our nation is the gap between high-quality care and the people who need it most. The passage of the Affordable Care Act was meant, in part, to reduce this gap and increase health equity in terms of both eligibility for, and access to, care. However, lower-income residents, especially those from minority groups, are more likely to be hospitalized for asthma, hypertension, heart disease, and diabetes, and to experience infertility, preterm birth, and fetal death.
Health disparities, or inequities, translate not only into greater suffering for certain segments of the population, but also to significantly greater health care costs for everyone. Racial health disparities are associated with an estimated $35 billion annually in excess expenditures, $10 billion in lost productivity, and nearly $200 billion in premature deaths, according to an article in the Harvard Business Review. A 2013 study estimated that reducing racial disparities in adverse pregnancy outcomes – preeclampsia, preterm birth, gestational diabetes mellitus, and fetal death/stillbirth – could generate health care cost savings of up to $214 million per year (Matern Child Health J. 2013 Oct;17[8]:1518-25).
Several years ago, the State of Maryland took a unique approach to reducing health disparities by passing the Maryland Health Improvement and Disparities Reduction Act. One of the major components of this legislation was the creation of Health Enterprise Zones (HEZs), distinct geographical areas across the state dedicated to addressing health disparities and improving access to high-quality care. This incentive-based program provides state-funded resources to primary care providers and community-based health organizations specifically to help the neighborhoods they serve. I was deeply honored to serve as chairman of the task force that recommended the establishment of the HEZs.
For this Master Class, I have invited Melissa A. Simon, MD, the George H. Gardner, MD, Professor of Clinical Gynecology and professor of obstetrics and gynecology at Northwestern University, Chicago, to provide some practical advice on how to create greater health equity.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Electronic fetal monitoring: Is it information overload?
There is no question that we are living in the information age where “big data” isn’t just reserved for scientists but is accessible to everyone. Wearable devices have revolutionized when and how often we exercise. Smartphones have changed the way in which we consume news, watch television, take photographs, and record home movies. Online video chatting has allowed people who live miles – or even countries – away to connect on a whole new level. Today’s 7-year-olds have never lived in a world without iPhones and don’t know what life is like without iPads. Technology has improved our daily lives in countless ways. However, is “too much of a good thing” ever just too much?
Last year, we looked back over the preceding 5 decades of ob.gyn. practice. This retrospective analysis demonstrated that today’s practitioners have infinitely more tools at their disposal than many of their mentors did to ensure the best pregnancy outcomes. From prenatal diagnostic approaches, such as ultrasonography and genetic screening, to in utero surgical interventions, our discipline has advanced in leaps and bounds, all over the course of one person’s lifetime.
As technology continues to change and, in many ways, enhance the patient experience, the question we should continually ask is, “just because we can do something, should we do it?” Just because we can perform a chorionic villus sampling, should we perform one? Perhaps not. Just because we can schedule a planned cesarean section, should we? Probably not. The same line of questioning applies to the tools we employ to assist us in labor and delivery, including one of the most ubiquitous ones – the electronic fetal monitor.
The electronic fetal heart rate monitor was developed in the late 1950s to continuously record the fetal heart rate during delivery and to help ob.gyns. identify patterns that might indicate fetal distress. Although the monitors have improved over time, the interpretation of the data obtained, and what measures to employ based on these data, can be unclear. Just because the electronic fetal monitor can detect an abnormal heart rate pattern, should we intervene, and what approaches should we employ?
To help answer these questions, I have invited Dr. Alison G. Cahill, associate professor in the department of obstetrics and gynecology at Washington University, St. Louis, and chief of the division of maternal-fetal medicine, to explore the use, utility, and interpretation of data obtained by electronic fetal monitors.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
There is no question that we are living in the information age where “big data” isn’t just reserved for scientists but is accessible to everyone. Wearable devices have revolutionized when and how often we exercise. Smartphones have changed the way in which we consume news, watch television, take photographs, and record home movies. Online video chatting has allowed people who live miles – or even countries – away to connect on a whole new level. Today’s 7-year-olds have never lived in a world without iPhones and don’t know what life is like without iPads. Technology has improved our daily lives in countless ways. However, is “too much of a good thing” ever just too much?
Last year, we looked back over the preceding 5 decades of ob.gyn. practice. This retrospective analysis demonstrated that today’s practitioners have infinitely more tools at their disposal than many of their mentors did to ensure the best pregnancy outcomes. From prenatal diagnostic approaches, such as ultrasonography and genetic screening, to in utero surgical interventions, our discipline has advanced in leaps and bounds, all over the course of one person’s lifetime.
As technology continues to change and, in many ways, enhance the patient experience, the question we should continually ask is, “just because we can do something, should we do it?” Just because we can perform a chorionic villus sampling, should we perform one? Perhaps not. Just because we can schedule a planned cesarean section, should we? Probably not. The same line of questioning applies to the tools we employ to assist us in labor and delivery, including one of the most ubiquitous ones – the electronic fetal monitor.
The electronic fetal heart rate monitor was developed in the late 1950s to continuously record the fetal heart rate during delivery and to help ob.gyns. identify patterns that might indicate fetal distress. Although the monitors have improved over time, the interpretation of the data obtained, and what measures to employ based on these data, can be unclear. Just because the electronic fetal monitor can detect an abnormal heart rate pattern, should we intervene, and what approaches should we employ?
To help answer these questions, I have invited Dr. Alison G. Cahill, associate professor in the department of obstetrics and gynecology at Washington University, St. Louis, and chief of the division of maternal-fetal medicine, to explore the use, utility, and interpretation of data obtained by electronic fetal monitors.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
There is no question that we are living in the information age where “big data” isn’t just reserved for scientists but is accessible to everyone. Wearable devices have revolutionized when and how often we exercise. Smartphones have changed the way in which we consume news, watch television, take photographs, and record home movies. Online video chatting has allowed people who live miles – or even countries – away to connect on a whole new level. Today’s 7-year-olds have never lived in a world without iPhones and don’t know what life is like without iPads. Technology has improved our daily lives in countless ways. However, is “too much of a good thing” ever just too much?
Last year, we looked back over the preceding 5 decades of ob.gyn. practice. This retrospective analysis demonstrated that today’s practitioners have infinitely more tools at their disposal than many of their mentors did to ensure the best pregnancy outcomes. From prenatal diagnostic approaches, such as ultrasonography and genetic screening, to in utero surgical interventions, our discipline has advanced in leaps and bounds, all over the course of one person’s lifetime.
As technology continues to change and, in many ways, enhance the patient experience, the question we should continually ask is, “just because we can do something, should we do it?” Just because we can perform a chorionic villus sampling, should we perform one? Perhaps not. Just because we can schedule a planned cesarean section, should we? Probably not. The same line of questioning applies to the tools we employ to assist us in labor and delivery, including one of the most ubiquitous ones – the electronic fetal monitor.
The electronic fetal heart rate monitor was developed in the late 1950s to continuously record the fetal heart rate during delivery and to help ob.gyns. identify patterns that might indicate fetal distress. Although the monitors have improved over time, the interpretation of the data obtained, and what measures to employ based on these data, can be unclear. Just because the electronic fetal monitor can detect an abnormal heart rate pattern, should we intervene, and what approaches should we employ?
To help answer these questions, I have invited Dr. Alison G. Cahill, associate professor in the department of obstetrics and gynecology at Washington University, St. Louis, and chief of the division of maternal-fetal medicine, to explore the use, utility, and interpretation of data obtained by electronic fetal monitors.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Prenatal surveillance vital in monochorionic twin pregnancies
Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.
The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.
This month, we focus on the range of tools and approaches used to treat complications that can occur in monochorionic twin pregnancies, including twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion. Despite the challenges these conditions pose, increased ultrasonographic and echocardiographic surveillance allow for earlier detection and possible intervention to slow progression or, in some cases, correct defects that would have terminated the pregnancy not too long ago. Additionally, fetal therapy programs utilizing in-utero surgical techniques, such as fetoscopic laser coagulation, have significantly broadened the management and treatment options we can now offer these patients.
Dr. M. Ozhan Turan, an associate professor and director of fetal therapy and complex obstetric surgery in the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, provides an overview of these techniques and technologies which, when applied appropriately, can significantly improve pregnancy outcomes.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.
The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.
This month, we focus on the range of tools and approaches used to treat complications that can occur in monochorionic twin pregnancies, including twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion. Despite the challenges these conditions pose, increased ultrasonographic and echocardiographic surveillance allow for earlier detection and possible intervention to slow progression or, in some cases, correct defects that would have terminated the pregnancy not too long ago. Additionally, fetal therapy programs utilizing in-utero surgical techniques, such as fetoscopic laser coagulation, have significantly broadened the management and treatment options we can now offer these patients.
Dr. M. Ozhan Turan, an associate professor and director of fetal therapy and complex obstetric surgery in the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, provides an overview of these techniques and technologies which, when applied appropriately, can significantly improve pregnancy outcomes.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.
The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.
This month, we focus on the range of tools and approaches used to treat complications that can occur in monochorionic twin pregnancies, including twin-to-twin transfusion syndrome, selective fetal growth restriction, twin anemia polycythemia sequence, and twin reversed arterial perfusion. Despite the challenges these conditions pose, increased ultrasonographic and echocardiographic surveillance allow for earlier detection and possible intervention to slow progression or, in some cases, correct defects that would have terminated the pregnancy not too long ago. Additionally, fetal therapy programs utilizing in-utero surgical techniques, such as fetoscopic laser coagulation, have significantly broadened the management and treatment options we can now offer these patients.
Dr. M. Ozhan Turan, an associate professor and director of fetal therapy and complex obstetric surgery in the department of obstetrics, gynecology, and reproductive sciences at the University of Maryland School of Medicine, provides an overview of these techniques and technologies which, when applied appropriately, can significantly improve pregnancy outcomes.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Alarming gaps in gestational diabetes care
BY E. ALBERT REECE, MD, PhD, MBA
Much attention has been given in the media to the incidence of prediabetes in the general population. The Centers for Disease Control and Prevention estimates that approximately 86 million adults have prediabetes, and that the incidence of this condition is similar across racial and ethnic groups. Indeed, the seriousness of this public health concern prompted the Centers for Medicare & Medicaid Services to expand Medicare coverage for interventions for people with prediabetes, a move that was finalized in November 2016.
Despite a widespread focus on the need to prevent prediabetes from becoming type 2 diabetes, women diagnosed with gestational diabetes mellitus (GDM), which accounts for about 9% of women in the United States, may not be receiving critical advice and care.
The investigators analyzed data collected via the National Health and Nutrition Examination Survey from 2007-2012, and identified 284 women with a history of GDM. Only 67% of these women received diabetes screening, and approximately one-third of women included in the study had undiagnosed prediabetes and diabetes. The authors concluded that prediabetes in women who have had GDM may be underdiagnosed. They argued that women with GDM should be encouraged to have additional health visits and screenings to prevent the development of prediabetes or diabetes. Considering the fact that a number of studies have shown that GDM predisposes a woman to developing type 2 diabetes, the University of Illinois findings are alarming.
As ob.gyns., we have increasingly become a woman’s only health care practitioner. Although individuals may skip annual exams with a primary care physician, during which blood work is typically drawn, many women will see their ob.gyn. for regular check-ups. Therefore, we have a unique role to play in our patients’ lifelong health. This is especially important during pregnancy, when it may be easy to focus only on the mother’s health as it pertains to the health of the baby, rather than her health in pregnancy as it may affect her long-term well-being.
We have invited Robert Ratner, MD, the chief scientific and medical officer at the American Diabetes Association, to discuss the need to carefully follow up with patients who have had GDM and to educate them about their risk for developing type 2 diabetes later in life.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Why postpartum GDM follow-up is so important
BY ROBERT E. RATNER, MD
Much of the attention paid to diagnosing gestational diabetes has focused on the fetus and on babies being born very large. However, it is important to appreciate that the original definitions of the condition were based entirely on the long-term outcomes of the mother.
John O’Sullivan, MD, and statistician Claire Mahan published diagnostic criteria in 1964 after performing 3-hour oral glucose tolerance tests (OGTTs) in more than 500 unselected women during their pregnancies, and then following these women and babies out as far as 23 years. Retrospectively, Dr. O’Sullivan and Ms. Mahan defined gestational diabetes mellitus (GDM) as glucose values exceeding two standard deviations above the mean on two out of four OGTT values. 
They came to their conclusions after tracking the later development of diabetes outside of pregnancy. More than 20 years later, 70% of women with the higher OGTT values had developed type 2 diabetes, compared with approximately 10% of women who did not have higher values during pregnancy. The O’Sullivan criteria were established, essentially, based on their association with the development of diabetes after pregnancy. In addition to being a significant predictor of subsequent diabetes, a history of GDM also conferred a three- to fourfold increase in maternal mortality.
Fifty-some years later, these findings have been affirmed through additional research and are the crux of what drives the current recommendations for postpartum follow-up of women with a history of GDM.
Long-term maternal risks
Postpartum, the current recommendation from both the American Diabetes Association and the American College of Obstetricians and Gynecologists is that women with GDM be tested at 6-12 weeks after delivery to ensure that the diabetes has resolved.
This recommendation for initial postpartum testing carries with it a stipulation that’s different from subsequent postpartum testing. It says that postpartum testing at 6-12 weeks should be performed with either a fasting glucose test or a 2-hour OGTT. Since hemoglobin A1c may still be impacted by the rapid red blood cell turnover in pregnancy or blood loss at delivery, A1c testing lacks sensitivity for identifying diabetes during this window of time.
Initial postpartum testing also serves as a way to identify whether the diabetes during pregnancy was preexisting or purely secondary to the hormonal changes associated with the pregnancy.
If this first postpartum test shows diabetes, the patient most likely had preexisting diabetes, and therapy must be initiated immediately. In the case of a normal result, the patient remains at higher risk for the development of type 2 diabetes essentially for the rest of her life and should be tested at least every 3 years for the occurrence of the disease.
Much of the increased risk for different ethnic groups occurs within 5 years of the index pregnancy. This was shown in a systematic review led by Catherine Kim, MD; the review examined more than two dozen studies with follow-up of up to 28 years postpartum. The cumulative incidence of type 2 diabetes increased markedly in the first 5 years and then appeared to plateau after 10 years (Diabetes Care. 2002 Oct;25[10]:1862-8).
The best data on late-occurring diabetes following GDM comes from the multicenter National Institutes of Health–sponsored Diabetes Prevention Program (DPP) trial, which randomized more than 3,000 individuals with baseline impaired glucose tolerance – or prediabetes – to one of two interventions: metformin therapy or intensive lifestyle intervention, or to placebo.
Within this population, there were more than 1,700 women who had a previous live birth. Of these women, 350 reported a history of GDM at a mean of 12 years since the delivery of their first GDM pregnancy. The DPP gave us the opportunity, therefore, to look at a large group of women about 12 years away from their GDM pregnancy who had abnormal glucose levels but had not reached the level of type 2 diabetes, and compare them with women with similarly impaired glucose tolerance who did not have a history of GDM.
There were interesting similarities and differences. Women with a GDM history were on average 8 years younger than women without a GDM history, but they had comparable BMIs. In addition, within the placebo arm, we could observe the natural history of glucose intolerance in women with and without a history of GDM. Despite both groups entering the study with equivalent degrees of impaired glucose tolerance and similar BMI, women with a history of GDM had a 71% higher risk of developing diabetes during the 3-year intervention period than that of parous women without a history of GDM (J Clin Endocrinol Metab. 2008 Dec;93[12]:4774-9).
Clearly, there was something about the history of GDM that puts these women at greater risk for diabetes than women who had the same impaired glucose tolerance, but no GDM. The study demonstrated that GDM is an exceptionally strong predictor of the development of type 2 diabetes, even for those who manage to escape diabetes for the first 10 years.
Postpartum prevention
The DPP demonstrated, moreover, that intensive lifestyle therapy and metformin not only were both effective, but that they were equally effective, in delaying or preventing diabetes in women with impaired glucose tolerance and a history of GDM. Both reduced the risk by about 50% at 3 years. This was striking because in parous women without GDM, the reductions were 49% and 14%, respectively. Metformin thus appeared to be more effective in women with a history of GDM.
The effects of the interventions persisted over a 10-year follow up of the DPP population. In women with a history of GDM, the intensive lifestyle intervention and metformin reduced progression to diabetes by 35% and 40%, respectively, over 10 years (J Clin Endocrinol Metab. 2015 Apr;100[4]:1646-53).
Pregnancy presents a stress test for beta cell function, and gestational diabetes clearly is a harbinger of further deterioration in beta-cell function and metabolic abnormalities in the mother. Because of these risks and because early intervention makes a difference, surveillance is critically important. Most women see their ob.gyn. as their primary care physician in the 10 years following a pregnancy – the time when more than 50% of all cases of subsequent diabetes will occur – and many continue to see their ob.gyns. in the longer term, as their risk continues to linger.
Immediately after a pregnancy with GDM, ob.gyns. can counsel women not only about their risks of developing type 2 diabetes and the importance of screening, but also about the beneficial impact of lifestyle modification, caloric restriction and weight loss if necessary, and increased exercise. Mothers should also know that GDM is a family affair, and that lifestyle changes that are beneficial for the mother will be equally beneficial for the baby.
The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study taught us that there are continuous linear relationships between maternal glucose and adverse fetal outcomes like birth weight and percent body fat greater than the 90th percentile. Longitudinal studies of the Pima Indians showed us that offspring of women who had diabetes during pregnancy were more likely to be obese and more likely to develop diabetes than offspring of women who did not have diabetes during pregnancy. Even when GDM has been well treated and controlled, we should have heightened awareness to the potential risks in the fetus and the growing child and adolescent.
Patients who are found to have subsequent type 2 diabetes should know that aggressive therapy early on in the natural history of the disease reduces the risk of microvascular and macrovascular complications. And as the DPP has demonstrated, lifestyle interventions and metformin may also keep women who are found to have prediabetes outside of pregnancy from progressing on to diabetes.
Dr. Ratner is the chief scientific and medical officer for the American Diabetes Association. He reported having no financial disclosures relevant to this Master Class.
BY E. ALBERT REECE, MD, PhD, MBA
Much attention has been given in the media to the incidence of prediabetes in the general population. The Centers for Disease Control and Prevention estimates that approximately 86 million adults have prediabetes, and that the incidence of this condition is similar across racial and ethnic groups. Indeed, the seriousness of this public health concern prompted the Centers for Medicare & Medicaid Services to expand Medicare coverage for interventions for people with prediabetes, a move that was finalized in November 2016.
Despite a widespread focus on the need to prevent prediabetes from becoming type 2 diabetes, women diagnosed with gestational diabetes mellitus (GDM), which accounts for about 9% of women in the United States, may not be receiving critical advice and care.
The investigators analyzed data collected via the National Health and Nutrition Examination Survey from 2007-2012, and identified 284 women with a history of GDM. Only 67% of these women received diabetes screening, and approximately one-third of women included in the study had undiagnosed prediabetes and diabetes. The authors concluded that prediabetes in women who have had GDM may be underdiagnosed. They argued that women with GDM should be encouraged to have additional health visits and screenings to prevent the development of prediabetes or diabetes. Considering the fact that a number of studies have shown that GDM predisposes a woman to developing type 2 diabetes, the University of Illinois findings are alarming.
As ob.gyns., we have increasingly become a woman’s only health care practitioner. Although individuals may skip annual exams with a primary care physician, during which blood work is typically drawn, many women will see their ob.gyn. for regular check-ups. Therefore, we have a unique role to play in our patients’ lifelong health. This is especially important during pregnancy, when it may be easy to focus only on the mother’s health as it pertains to the health of the baby, rather than her health in pregnancy as it may affect her long-term well-being.
We have invited Robert Ratner, MD, the chief scientific and medical officer at the American Diabetes Association, to discuss the need to carefully follow up with patients who have had GDM and to educate them about their risk for developing type 2 diabetes later in life.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Why postpartum GDM follow-up is so important
BY ROBERT E. RATNER, MD
Much of the attention paid to diagnosing gestational diabetes has focused on the fetus and on babies being born very large. However, it is important to appreciate that the original definitions of the condition were based entirely on the long-term outcomes of the mother.
John O’Sullivan, MD, and statistician Claire Mahan published diagnostic criteria in 1964 after performing 3-hour oral glucose tolerance tests (OGTTs) in more than 500 unselected women during their pregnancies, and then following these women and babies out as far as 23 years. Retrospectively, Dr. O’Sullivan and Ms. Mahan defined gestational diabetes mellitus (GDM) as glucose values exceeding two standard deviations above the mean on two out of four OGTT values.
They came to their conclusions after tracking the later development of diabetes outside of pregnancy. More than 20 years later, 70% of women with the higher OGTT values had developed type 2 diabetes, compared with approximately 10% of women who did not have higher values during pregnancy. The O’Sullivan criteria were established, essentially, based on their association with the development of diabetes after pregnancy. In addition to being a significant predictor of subsequent diabetes, a history of GDM also conferred a three- to fourfold increase in maternal mortality.
Fifty-some years later, these findings have been affirmed through additional research and are the crux of what drives the current recommendations for postpartum follow-up of women with a history of GDM.
Long-term maternal risks
Postpartum, the current recommendation from both the American Diabetes Association and the American College of Obstetricians and Gynecologists is that women with GDM be tested at 6-12 weeks after delivery to ensure that the diabetes has resolved.
This recommendation for initial postpartum testing carries with it a stipulation that’s different from subsequent postpartum testing. It says that postpartum testing at 6-12 weeks should be performed with either a fasting glucose test or a 2-hour OGTT. Since hemoglobin A1c may still be impacted by the rapid red blood cell turnover in pregnancy or blood loss at delivery, A1c testing lacks sensitivity for identifying diabetes during this window of time.
Initial postpartum testing also serves as a way to identify whether the diabetes during pregnancy was preexisting or purely secondary to the hormonal changes associated with the pregnancy.
If this first postpartum test shows diabetes, the patient most likely had preexisting diabetes, and therapy must be initiated immediately. In the case of a normal result, the patient remains at higher risk for the development of type 2 diabetes essentially for the rest of her life and should be tested at least every 3 years for the occurrence of the disease.
Much of the increased risk for different ethnic groups occurs within 5 years of the index pregnancy. This was shown in a systematic review led by Catherine Kim, MD; the review examined more than two dozen studies with follow-up of up to 28 years postpartum. The cumulative incidence of type 2 diabetes increased markedly in the first 5 years and then appeared to plateau after 10 years (Diabetes Care. 2002 Oct;25[10]:1862-8).
The best data on late-occurring diabetes following GDM comes from the multicenter National Institutes of Health–sponsored Diabetes Prevention Program (DPP) trial, which randomized more than 3,000 individuals with baseline impaired glucose tolerance – or prediabetes – to one of two interventions: metformin therapy or intensive lifestyle intervention, or to placebo.
Within this population, there were more than 1,700 women who had a previous live birth. Of these women, 350 reported a history of GDM at a mean of 12 years since the delivery of their first GDM pregnancy. The DPP gave us the opportunity, therefore, to look at a large group of women about 12 years away from their GDM pregnancy who had abnormal glucose levels but had not reached the level of type 2 diabetes, and compare them with women with similarly impaired glucose tolerance who did not have a history of GDM.
There were interesting similarities and differences. Women with a GDM history were on average 8 years younger than women without a GDM history, but they had comparable BMIs. In addition, within the placebo arm, we could observe the natural history of glucose intolerance in women with and without a history of GDM. Despite both groups entering the study with equivalent degrees of impaired glucose tolerance and similar BMI, women with a history of GDM had a 71% higher risk of developing diabetes during the 3-year intervention period than that of parous women without a history of GDM (J Clin Endocrinol Metab. 2008 Dec;93[12]:4774-9).
Clearly, there was something about the history of GDM that puts these women at greater risk for diabetes than women who had the same impaired glucose tolerance, but no GDM. The study demonstrated that GDM is an exceptionally strong predictor of the development of type 2 diabetes, even for those who manage to escape diabetes for the first 10 years.
Postpartum prevention
The DPP demonstrated, moreover, that intensive lifestyle therapy and metformin not only were both effective, but that they were equally effective, in delaying or preventing diabetes in women with impaired glucose tolerance and a history of GDM. Both reduced the risk by about 50% at 3 years. This was striking because in parous women without GDM, the reductions were 49% and 14%, respectively. Metformin thus appeared to be more effective in women with a history of GDM.
The effects of the interventions persisted over a 10-year follow up of the DPP population. In women with a history of GDM, the intensive lifestyle intervention and metformin reduced progression to diabetes by 35% and 40%, respectively, over 10 years (J Clin Endocrinol Metab. 2015 Apr;100[4]:1646-53).
Pregnancy presents a stress test for beta cell function, and gestational diabetes clearly is a harbinger of further deterioration in beta-cell function and metabolic abnormalities in the mother. Because of these risks and because early intervention makes a difference, surveillance is critically important. Most women see their ob.gyn. as their primary care physician in the 10 years following a pregnancy – the time when more than 50% of all cases of subsequent diabetes will occur – and many continue to see their ob.gyns. in the longer term, as their risk continues to linger.
Immediately after a pregnancy with GDM, ob.gyns. can counsel women not only about their risks of developing type 2 diabetes and the importance of screening, but also about the beneficial impact of lifestyle modification, caloric restriction and weight loss if necessary, and increased exercise. Mothers should also know that GDM is a family affair, and that lifestyle changes that are beneficial for the mother will be equally beneficial for the baby.
The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study taught us that there are continuous linear relationships between maternal glucose and adverse fetal outcomes like birth weight and percent body fat greater than the 90th percentile. Longitudinal studies of the Pima Indians showed us that offspring of women who had diabetes during pregnancy were more likely to be obese and more likely to develop diabetes than offspring of women who did not have diabetes during pregnancy. Even when GDM has been well treated and controlled, we should have heightened awareness to the potential risks in the fetus and the growing child and adolescent.
Patients who are found to have subsequent type 2 diabetes should know that aggressive therapy early on in the natural history of the disease reduces the risk of microvascular and macrovascular complications. And as the DPP has demonstrated, lifestyle interventions and metformin may also keep women who are found to have prediabetes outside of pregnancy from progressing on to diabetes.
Dr. Ratner is the chief scientific and medical officer for the American Diabetes Association. He reported having no financial disclosures relevant to this Master Class.
BY E. ALBERT REECE, MD, PhD, MBA
Much attention has been given in the media to the incidence of prediabetes in the general population. The Centers for Disease Control and Prevention estimates that approximately 86 million adults have prediabetes, and that the incidence of this condition is similar across racial and ethnic groups. Indeed, the seriousness of this public health concern prompted the Centers for Medicare & Medicaid Services to expand Medicare coverage for interventions for people with prediabetes, a move that was finalized in November 2016.
Despite a widespread focus on the need to prevent prediabetes from becoming type 2 diabetes, women diagnosed with gestational diabetes mellitus (GDM), which accounts for about 9% of women in the United States, may not be receiving critical advice and care.
The investigators analyzed data collected via the National Health and Nutrition Examination Survey from 2007-2012, and identified 284 women with a history of GDM. Only 67% of these women received diabetes screening, and approximately one-third of women included in the study had undiagnosed prediabetes and diabetes. The authors concluded that prediabetes in women who have had GDM may be underdiagnosed. They argued that women with GDM should be encouraged to have additional health visits and screenings to prevent the development of prediabetes or diabetes. Considering the fact that a number of studies have shown that GDM predisposes a woman to developing type 2 diabetes, the University of Illinois findings are alarming.
As ob.gyns., we have increasingly become a woman’s only health care practitioner. Although individuals may skip annual exams with a primary care physician, during which blood work is typically drawn, many women will see their ob.gyn. for regular check-ups. Therefore, we have a unique role to play in our patients’ lifelong health. This is especially important during pregnancy, when it may be easy to focus only on the mother’s health as it pertains to the health of the baby, rather than her health in pregnancy as it may affect her long-term well-being.
We have invited Robert Ratner, MD, the chief scientific and medical officer at the American Diabetes Association, to discuss the need to carefully follow up with patients who have had GDM and to educate them about their risk for developing type 2 diabetes later in life.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Why postpartum GDM follow-up is so important
BY ROBERT E. RATNER, MD
Much of the attention paid to diagnosing gestational diabetes has focused on the fetus and on babies being born very large. However, it is important to appreciate that the original definitions of the condition were based entirely on the long-term outcomes of the mother.
John O’Sullivan, MD, and statistician Claire Mahan published diagnostic criteria in 1964 after performing 3-hour oral glucose tolerance tests (OGTTs) in more than 500 unselected women during their pregnancies, and then following these women and babies out as far as 23 years. Retrospectively, Dr. O’Sullivan and Ms. Mahan defined gestational diabetes mellitus (GDM) as glucose values exceeding two standard deviations above the mean on two out of four OGTT values.
They came to their conclusions after tracking the later development of diabetes outside of pregnancy. More than 20 years later, 70% of women with the higher OGTT values had developed type 2 diabetes, compared with approximately 10% of women who did not have higher values during pregnancy. The O’Sullivan criteria were established, essentially, based on their association with the development of diabetes after pregnancy. In addition to being a significant predictor of subsequent diabetes, a history of GDM also conferred a three- to fourfold increase in maternal mortality.
Fifty-some years later, these findings have been affirmed through additional research and are the crux of what drives the current recommendations for postpartum follow-up of women with a history of GDM.
Long-term maternal risks
Postpartum, the current recommendation from both the American Diabetes Association and the American College of Obstetricians and Gynecologists is that women with GDM be tested at 6-12 weeks after delivery to ensure that the diabetes has resolved.
This recommendation for initial postpartum testing carries with it a stipulation that’s different from subsequent postpartum testing. It says that postpartum testing at 6-12 weeks should be performed with either a fasting glucose test or a 2-hour OGTT. Since hemoglobin A1c may still be impacted by the rapid red blood cell turnover in pregnancy or blood loss at delivery, A1c testing lacks sensitivity for identifying diabetes during this window of time.
Initial postpartum testing also serves as a way to identify whether the diabetes during pregnancy was preexisting or purely secondary to the hormonal changes associated with the pregnancy.
If this first postpartum test shows diabetes, the patient most likely had preexisting diabetes, and therapy must be initiated immediately. In the case of a normal result, the patient remains at higher risk for the development of type 2 diabetes essentially for the rest of her life and should be tested at least every 3 years for the occurrence of the disease.
Much of the increased risk for different ethnic groups occurs within 5 years of the index pregnancy. This was shown in a systematic review led by Catherine Kim, MD; the review examined more than two dozen studies with follow-up of up to 28 years postpartum. The cumulative incidence of type 2 diabetes increased markedly in the first 5 years and then appeared to plateau after 10 years (Diabetes Care. 2002 Oct;25[10]:1862-8).
The best data on late-occurring diabetes following GDM comes from the multicenter National Institutes of Health–sponsored Diabetes Prevention Program (DPP) trial, which randomized more than 3,000 individuals with baseline impaired glucose tolerance – or prediabetes – to one of two interventions: metformin therapy or intensive lifestyle intervention, or to placebo.
Within this population, there were more than 1,700 women who had a previous live birth. Of these women, 350 reported a history of GDM at a mean of 12 years since the delivery of their first GDM pregnancy. The DPP gave us the opportunity, therefore, to look at a large group of women about 12 years away from their GDM pregnancy who had abnormal glucose levels but had not reached the level of type 2 diabetes, and compare them with women with similarly impaired glucose tolerance who did not have a history of GDM.
There were interesting similarities and differences. Women with a GDM history were on average 8 years younger than women without a GDM history, but they had comparable BMIs. In addition, within the placebo arm, we could observe the natural history of glucose intolerance in women with and without a history of GDM. Despite both groups entering the study with equivalent degrees of impaired glucose tolerance and similar BMI, women with a history of GDM had a 71% higher risk of developing diabetes during the 3-year intervention period than that of parous women without a history of GDM (J Clin Endocrinol Metab. 2008 Dec;93[12]:4774-9).
Clearly, there was something about the history of GDM that puts these women at greater risk for diabetes than women who had the same impaired glucose tolerance, but no GDM. The study demonstrated that GDM is an exceptionally strong predictor of the development of type 2 diabetes, even for those who manage to escape diabetes for the first 10 years.
Postpartum prevention
The DPP demonstrated, moreover, that intensive lifestyle therapy and metformin not only were both effective, but that they were equally effective, in delaying or preventing diabetes in women with impaired glucose tolerance and a history of GDM. Both reduced the risk by about 50% at 3 years. This was striking because in parous women without GDM, the reductions were 49% and 14%, respectively. Metformin thus appeared to be more effective in women with a history of GDM.
The effects of the interventions persisted over a 10-year follow up of the DPP population. In women with a history of GDM, the intensive lifestyle intervention and metformin reduced progression to diabetes by 35% and 40%, respectively, over 10 years (J Clin Endocrinol Metab. 2015 Apr;100[4]:1646-53).
Pregnancy presents a stress test for beta cell function, and gestational diabetes clearly is a harbinger of further deterioration in beta-cell function and metabolic abnormalities in the mother. Because of these risks and because early intervention makes a difference, surveillance is critically important. Most women see their ob.gyn. as their primary care physician in the 10 years following a pregnancy – the time when more than 50% of all cases of subsequent diabetes will occur – and many continue to see their ob.gyns. in the longer term, as their risk continues to linger.
Immediately after a pregnancy with GDM, ob.gyns. can counsel women not only about their risks of developing type 2 diabetes and the importance of screening, but also about the beneficial impact of lifestyle modification, caloric restriction and weight loss if necessary, and increased exercise. Mothers should also know that GDM is a family affair, and that lifestyle changes that are beneficial for the mother will be equally beneficial for the baby.
The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study taught us that there are continuous linear relationships between maternal glucose and adverse fetal outcomes like birth weight and percent body fat greater than the 90th percentile. Longitudinal studies of the Pima Indians showed us that offspring of women who had diabetes during pregnancy were more likely to be obese and more likely to develop diabetes than offspring of women who did not have diabetes during pregnancy. Even when GDM has been well treated and controlled, we should have heightened awareness to the potential risks in the fetus and the growing child and adolescent.
Patients who are found to have subsequent type 2 diabetes should know that aggressive therapy early on in the natural history of the disease reduces the risk of microvascular and macrovascular complications. And as the DPP has demonstrated, lifestyle interventions and metformin may also keep women who are found to have prediabetes outside of pregnancy from progressing on to diabetes.
Dr. Ratner is the chief scientific and medical officer for the American Diabetes Association. He reported having no financial disclosures relevant to this Master Class.
The importance of studying the placenta
It makes logical, intellectual sense that the placenta, an organ that is so integrally involved in pregnancy, will be of such great importance to the well-being, sustenance, and growth and development of the fetus. After all, the placental compartment and fetal compartment have the same origin early in embryogenesis, and the placenta is the sole source of nutrients and oxygen for the fetus.
However, the placenta has been extraordinarily poorly understood. Much of medicine has regarded the placenta like the appendix – an organ that may be easily discarded. We know too little about its functions and its biology. We do not even know whether there is a minimum amount of placenta that’s necessary for fetal health.
Over the years, the National Institutes of Health (NIH) has placed an emphasis on certain key areas of study through efforts such as the Human Genome Project, the BRAIN Initiative, and the Cancer Moonshot. Such efforts involve sustained, fundamental research and usually lead to significant findings and subsequent application of the findings.
It is exciting to know that the NIH has launched its Human Placenta Project in an effort to better understand the biology of the placenta and to elucidate its functions. The technology that is employed will play an adjunctive role.
Fortunately, over the years various investigators have studied the placenta using ultrasound, color Doppler technology, and other techniques, and have reported important findings. The work of pathologist Carolyn M. Salafia, MD, and others has called attention to the importance of the shape and vasculature of the placenta, as well as blood flow.
To bring us up to date, as the NIH’s Human Placenta Project proceeds, I have asked Dr. Salafia to provide us with a review discussion of our current knowledge and its implications. Dr. Salafia specializes in reproductive and developmental pathology and reviews thousands of placentas each year through her work with various hospitals and as head of the Placental Modulation Laboratory at the Institute for Basic Research in Developmental Disabilities in Staten Island, N.Y.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
It makes logical, intellectual sense that the placenta, an organ that is so integrally involved in pregnancy, will be of such great importance to the well-being, sustenance, and growth and development of the fetus. After all, the placental compartment and fetal compartment have the same origin early in embryogenesis, and the placenta is the sole source of nutrients and oxygen for the fetus.
However, the placenta has been extraordinarily poorly understood. Much of medicine has regarded the placenta like the appendix – an organ that may be easily discarded. We know too little about its functions and its biology. We do not even know whether there is a minimum amount of placenta that’s necessary for fetal health.
Over the years, the National Institutes of Health (NIH) has placed an emphasis on certain key areas of study through efforts such as the Human Genome Project, the BRAIN Initiative, and the Cancer Moonshot. Such efforts involve sustained, fundamental research and usually lead to significant findings and subsequent application of the findings.
It is exciting to know that the NIH has launched its Human Placenta Project in an effort to better understand the biology of the placenta and to elucidate its functions. The technology that is employed will play an adjunctive role.
Fortunately, over the years various investigators have studied the placenta using ultrasound, color Doppler technology, and other techniques, and have reported important findings. The work of pathologist Carolyn M. Salafia, MD, and others has called attention to the importance of the shape and vasculature of the placenta, as well as blood flow.
To bring us up to date, as the NIH’s Human Placenta Project proceeds, I have asked Dr. Salafia to provide us with a review discussion of our current knowledge and its implications. Dr. Salafia specializes in reproductive and developmental pathology and reviews thousands of placentas each year through her work with various hospitals and as head of the Placental Modulation Laboratory at the Institute for Basic Research in Developmental Disabilities in Staten Island, N.Y.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
It makes logical, intellectual sense that the placenta, an organ that is so integrally involved in pregnancy, will be of such great importance to the well-being, sustenance, and growth and development of the fetus. After all, the placental compartment and fetal compartment have the same origin early in embryogenesis, and the placenta is the sole source of nutrients and oxygen for the fetus.
However, the placenta has been extraordinarily poorly understood. Much of medicine has regarded the placenta like the appendix – an organ that may be easily discarded. We know too little about its functions and its biology. We do not even know whether there is a minimum amount of placenta that’s necessary for fetal health.
Over the years, the National Institutes of Health (NIH) has placed an emphasis on certain key areas of study through efforts such as the Human Genome Project, the BRAIN Initiative, and the Cancer Moonshot. Such efforts involve sustained, fundamental research and usually lead to significant findings and subsequent application of the findings.
It is exciting to know that the NIH has launched its Human Placenta Project in an effort to better understand the biology of the placenta and to elucidate its functions. The technology that is employed will play an adjunctive role.
Fortunately, over the years various investigators have studied the placenta using ultrasound, color Doppler technology, and other techniques, and have reported important findings. The work of pathologist Carolyn M. Salafia, MD, and others has called attention to the importance of the shape and vasculature of the placenta, as well as blood flow.
To bring us up to date, as the NIH’s Human Placenta Project proceeds, I have asked Dr. Salafia to provide us with a review discussion of our current knowledge and its implications. Dr. Salafia specializes in reproductive and developmental pathology and reviews thousands of placentas each year through her work with various hospitals and as head of the Placental Modulation Laboratory at the Institute for Basic Research in Developmental Disabilities in Staten Island, N.Y.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Obstetrics Moonshots: 50 years of discoveries
In 1961 before Congress, and in 1962 at Rice University, Houston, President John F. Kennedy called on America to land a man on the moon and bring him back safely, and to look beyond the moon as well, and pursue an ambitious space exploration program. He challenged the country to think and act boldly, telling Americans in his speech at Rice that “we choose to go the moon in this decade and do the other things, not because they are easy, but because they are hard.”
When Neil Armstrong and Buzz Aldrin set foot on the moon in 1969 – even before President Kennedy’s 10-year deadline had arrived – the country’s primary moonshot was realized. The President had inspired the nation, teams of engineers and others had collectively met daunting technological challenges, and space consequently was more open to us than ever before.
In looking at the field of obstetrics and how far it has come in the past 50 years, since the 1960s, it is similarly astonishing and inspiring to reflect on what extraordinary advances we have made. Who would have thought that the fetus would become such a visible and intimate patient – one who, like the mother, can be interrogated, monitored, and sometimes treated before birth? Who would have thought we would be utilizing genomic studies in a now well-established field of prenatal diagnosis, or that fetal therapy would become a field in and of itself?
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Our specialty has advanced through a series of moonshots that have been inspired and driven by technological advancement and by our continually bold goals and vision for the health and well-being of women and their offspring. We have taken on ambitious challenges, achieved many goals, and embraced advancements in practice only to then set new targets that previously were unimaginable.
Yet just as our country’s space exploration program has faced disappointments, so has our field. It is sobering, for instance, that we have made only incremental improvements in prematurity and infant mortality, and that the age-old maternal problem of preeclampsia is still with us. We also face new challenges, such as the rising rate of maternal obesity and diabetes, which threaten both maternal and fetal health.
President Kennedy spoke of having “examined where we are strong, and where we are not.” Such self-reflection and assessment is a critical underpinning of advancement in fields across all of science, medicine, and health care, and in our specialty, it is a process that has driven ambitious new research efforts to improve fetal and maternal health.
A step back to more in-depth fundamental research on the biomolecular mechanisms of premature labor and diabetes-associated birth defects, for instance, as well as new efforts to approach fetal surgery less invasively, are positioning us to both conquer our disappointments and achieve ambitious new moonshots.
The fetus as our patient
Fifty years ago, in 1966, a seminal paper in the Lancet reported that amniotic fluid cells could be cultured and were suitable for karyotyping (1[7434]:383-5). The tapping and examination of amniotic fluid had been reported on sporadically for many decades, for various clinical purposes, but by and large the fetal compartment was not invaded or directly examined. The fetus was instead the hopeful beneficiary of pregnancy care that focused on the mother. Fetal outcome was clouded in mystery, known only at birth.
With the Lancet report, prenatal detection of chromosomal disorders began to feel achievable, and the 1960s marked the beginning of a journey first through invasive methods of prenatal diagnosis and then through increasingly non-invasive approaches.
In 1970, just several years after the report on chromosome analysis of amniotic-fluid cells, another landmark paper in the New England Journal of Medicine described 162 amniocenteses performed between the 13th and 18th weeks of gestation and the detection of 10 cases of Down syndrome, as well as a few other cases of metabolic and other disorders (282[11]:596-9). This report provided an impetus for broader use of the procedure to detect neural tube defects, Down syndrome, and other abnormalities.
The adoption of amniocentesis for prenatal diagnosis still took some time, however. The procedure was used primarily early on to determine fetal lung maturity, and to predict the ability of the fetus to survive after delivery.
At the time, it was widely praised as an advanced method for evaluating the fetus. Yet, looking back, the early years of the procedure seem primitive. The procedure was done late in pregnancy and it was performed blindly, with the puncture site located either with external palpation of the uterus or with the assistance of static ultrasound. Patients who had scans would usually visit the radiologist, who would mark on the patient’s abdomen a suggested location for needle insertion. Upon the patient’s return, the obstetrician would then insert a needle into that spot, blindly and likely after the fetus had moved.
The development and adoption of real-time ultrasound was a revolutionary achievement. Ultrasound-guided amniocentesis was first described in 1972, 14 years after Ian Donald’s seminal paper introducing obstetric ultrasound was published in the Lancet (1958 Jun 7;1[7032]:1188-95).
As real-time ultrasound made its way into practice, it marked the true realization of a moonshot for obstetrics.
Not only could we simultaneously visualize the needle tip and place the needle safety, but we could see the real-time movement of the fetus, its activity, and the surrounding pockets of fluid. It was like looking up into the sky and seeing the stars for the first time. We could see fetal arrhythmia – not only hear it. With this window into the fetal compartment, we could visualize the fetal bowel migrating into the chest cavity due to a hole (hernia) in the diaphragm. We could visualize other malformations as well.
Chorionic villus sampling (CVS) was technically more difficult and took longer to evolve. For years, through the early 1980s, it was performed only at select centers throughout the country. Patients traveled for the procedure and faced relatively significant risks of complications.
By the end of the 1980s, however, with successive improvements in equipment and technique (including development of a transabdominal approach in addition to transvaginal) the procedure was deemed safe, effective, and acceptable for routine use. Fetoscopy, pioneered by John Hobbins, MD, and his colleagues at Yale University, New Haven, Conn., had also advanced and was being used to diagnose sickle cell anemia, Tay-Sachs disease, congenital fetal skin diseases, and other disorders.
With these advances and with our newfound ability to obtain and analyze a tissue sample earlier in pregnancy – even before a woman shared the news of her pregnancy, in some cases – it seemed that we had achieved our goals and may have even reached past the moon.
Yet there were other moonshots being pursued, including initiatives to make prenatal diagnosis less invasive. The discovery in 1997 of cell-free fetal DNA in maternal plasma and serum, for instance, was a pivotal development that opened the door for noninvasive prenatal testing.
This, and other advances in areas from biochemistry to ultrasound to genomic analysis, led to an array of prenatal diagnostic tools that today enable women and their physicians to assess the genetic, chromosomal, and biophysical aspects of their fetus considerably before the time of viability, and from both the maternal side and directly in the fetal compartment.
First-trimester screening is a current option, and we now have the ability to more selectively perform amniocentesis and CVS based on probability testing, and not solely on maternal age. Ultrasound technology now encompasses color Doppler, 3D and 4D imaging, and other techniques that can be used to assess the placenta, various structures inside the brain, and the heart, as well as blood flow through the ductus venosus.
Parents have called for and welcomed having the option of assessing the fetus in greater detail, and of having either assurance when anomalies are excluded or the opportunity to plan and make decisions when anomalies are detected.
Fetal surgery has been a natural extension of our unprecedented access to the fetus. Our ability to visualize malformations and their evolution led to animal studies that advanced our interest in arresting, correcting, or reversing fetal anomalies through in-utero interventions. In 1981, surgeons performed the first human open fetal surgery to correct congenital hydronephrosis.
Today, we can employ endoscopic laser ablation or laser coagulation to treat severe twin-to-twin syndrome, for instance, as well as other surgical techniques to repair defects such as congenital diaphragmatic hernia, lower urinary tract obstruction, and myelomeningocele. Such advances were unimaginable decades ago.
Old foes and new threats
Despite these advances in diagnosis and care, obstetrics faces unrealized moonshots – lingering challenges that, 50 years ago, we would have predicted would have been solved. Who would have thought that we would still have as high an infant mortality rate as we do, and that we would not be further along in solving the problem of prematurity? Our progress has been only incremental.
Fifty years ago, we lacked an understanding of the basic biology of preterm labor. Prematurity was viewed simply as term labor occurring too early, and many efforts were made over the years to halt the premature labor process through the use of various drugs and other therapeutics, with variable and minimally impactful levels of success.
In the last 25 years, and especially in the last decade, we have made greater efforts to better understand the biology of premature labor – to elucidate how and why it occurs – and we have come to understand that premature labor is very different physiologically from term labor.
Thanks to the work at the Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), led by Roberto Romero, MD, attention has consequently shifted toward prediction, identification of women at highest risk, and prevention of the onset of premature labor among those deemed to be at highest risk.
Cervical length in the mid-trimester is now a well-verified predictor of preterm birth, and vaginal progesterone has been shown to benefit women without other known risk factors who are diagnosed with a shortened cervical length.
We have consequently seen the preterm birth rate decline a bit. In 2013, the last year for which we have complete data, the preterm birth rate dropped to 11.4%, down from a high of 12.8% in 2006, according to the Centers for Disease Control and Prevention.
Infant mortality similarly remains unacceptably high, due largely to the high preterm birth rate and to our failure to significantly alter the prevalence of birth defects. In 2010, according to the CDC, the infant mortality rate in the U.S. was 6.1 deaths per 1,000 live births (compared with 6.87 in 2005), and the United States ranked 26th in infant mortality among countries belonging to the Organisation for Economic Co-operation and Development, despite the fact that we spend a significant portion of our gross domestic product (17.5% in 2014) on health care.
Birth defects have taken over as a leading cause of infant mortality after early newborn life, and while we’ve made some advancements in understanding and diagnosing them, the majority of causes of birth defects are still unknown.
On the maternal side of obstetrical care, our progress has similarly been more modest than we have hoped for. Preeclampsia remains a problem, for instance. Despite decades of research into its pathogenesis, our advancements have been only incremental, and the condition – particularly its severe form – continues to be a vexing and high-risk problem.
Added to such age-old foes, moreover, are the growing threats of maternal obesity and diabetes, two closely related and often chronic conditions that affect not only the health of the mother but the in-utero environment and the health of the fetus. Today, more than one-third of all adults in the U.S., and 34% of women aged 20-39 years, are obese, and almost 10% of the U.S. population has diabetes.
Both conditions are on the rise, and obstetrics is confronting an epidemic of “diabesity” that would not necessarily have been predicted 50 years ago. It is particularly alarming given our growing knowledge of how obesity can be programmed in-utero and essentially passed on from generation to generation, of how diabetes can negatively affect perinatal outcomes, and of how the two conditions can have an additive effect on fetal complications.
Achieving new moonshots
Concerted efforts in the past several decades to step back and try to understand the basic biology and physiology of term labor and of premature labor have better positioned our specialty to achieve the moonshot of significantly reducing the incidence of preterm birth.
Establishment in the mid-1980s of the NICHD’s Perinatology Research Branch was a major development in this regard, helping to build and direct research efforts, including basic laboratory science, toward questions about what triggers and propagates labor. There has been notable progress in the past decade, in particular, and our specialty is now on the right path toward development of therapeutic interventions for preventing prematurity.
Additionally, the NICHD’s recently launched Human Placenta Project is building upon the branch-sponsored animal and cell culture model systems of the placenta to allow researchers, for the first time, to monitor human placental health in real time. By more fully understanding the role of the placenta in health and disease, we will be able to better evaluate pregnancy risks and improve pregnancy outcomes.
We also are learning through research in the University of Maryland Birth Defects Research Laboratory, which I am privileged to direct, and at other facilities, that maternal hyperglycemia is a teratogen, creating insults that can trigger a series of developmental fetal defects. By studying the biomolecular mechanisms of hyperglycemia-induced birth defects and developing “molecular maps,” we expect to be able to develop strategies for preventing or mitigating the development of such anomalies. I hope and expect that these future advancements, combined with reductions in prematurity, will significantly impact the infant mortality rate.
Fetal therapy and surgery will also continue to advance, with a much more minimally invasive approach taken in the next 50 years to addressing the fetal condition without putting the mother at increased risk. Just as surgery in other fields has moved from open laparotomy to minimally invasive techniques, I believe we will develop endoscopic or laparoscopic means of correcting the various problems in-utero, such as the repair of neural tube defects and diaphragmatic hernias. It already appears likely that a fetoscopic approach to treating myelomeningocele can reduce maternal morbidity while achieving infant neurological outcomes that are at least as good as outcomes achieved with open fetal surgery.
We’re in a much different position than we were 50 years ago in that we have two patients – the mother and the fetus – with whom we can closely work. We also have a relatively new and urgent obligation to place our attention not only on women’s reproductive health, but on the general gynecologic state. Ob.gyns. often are the only primary care physicians whom women see for routine care, and the quality of our attention to their weight and their diabetes risk factors will have far-reaching consequences, both for them and for their offspring.
As we have since the 1960s, we will continue to set new moonshots and meet new challenges, working with each other and with our patients to evaluate where we are strong and where we must improve. We will persistently harness the power of technology, choosing to do the things that “are hard,” while stepping back as needed to ask and address fundamental questions.
As a result, I can envision the next 50 years as a revolutionary time period for obstetrics – a time in which current problems and disorders are abated or eliminated through a combination of genomics, microbiomics, and other technological advances. Someday in the future, we will look back on some of our many achievements and marvel at how we have transformed the unimaginable to reality.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Select advances through the years
1960s
1965: Siemens Corp. introduces first real-time ultrasound scanner.
1966: Lancet paper reports that amniotic fluid cells can be cultured and karyotyped.
1970s
1970: New England Journal of Medicine paper describes mid-trimester amniocenteses and detection of Down syndrome cases.
1972: Ultrasound-guided amniocentesis first described.
1973: Fetoscopy introduced.
1980s
1981: First human open fetal surgery to correct congenital hydronephrosis.
Early 1980s: Chorionic villus sampling introduced at select centers.
1985: Color Doppler incorporated into ultrasound.
1990s
1990: Embryoscopy first described.
Mid-1990s: 3D/4D ultrasound begins to assume major role in ob.gyn. imaging.1997: Discovery of cell-free fetal DNA in maternal plasma.
2000s
2003: MOMS (Management of Myelomeningocele Study) was launched.
2010s
2012: The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support cell-free DNA screening for women at increased risk of fetal aneuploidy.
2013: Preterm birth rate drops to 11.4%
2014: Diabetes incidence marks a 4-fold increase since 1980.
In 1961 before Congress, and in 1962 at Rice University, Houston, President John F. Kennedy called on America to land a man on the moon and bring him back safely, and to look beyond the moon as well, and pursue an ambitious space exploration program. He challenged the country to think and act boldly, telling Americans in his speech at Rice that “we choose to go the moon in this decade and do the other things, not because they are easy, but because they are hard.”
When Neil Armstrong and Buzz Aldrin set foot on the moon in 1969 – even before President Kennedy’s 10-year deadline had arrived – the country’s primary moonshot was realized. The President had inspired the nation, teams of engineers and others had collectively met daunting technological challenges, and space consequently was more open to us than ever before.
In looking at the field of obstetrics and how far it has come in the past 50 years, since the 1960s, it is similarly astonishing and inspiring to reflect on what extraordinary advances we have made. Who would have thought that the fetus would become such a visible and intimate patient – one who, like the mother, can be interrogated, monitored, and sometimes treated before birth? Who would have thought we would be utilizing genomic studies in a now well-established field of prenatal diagnosis, or that fetal therapy would become a field in and of itself?
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Our specialty has advanced through a series of moonshots that have been inspired and driven by technological advancement and by our continually bold goals and vision for the health and well-being of women and their offspring. We have taken on ambitious challenges, achieved many goals, and embraced advancements in practice only to then set new targets that previously were unimaginable.
Yet just as our country’s space exploration program has faced disappointments, so has our field. It is sobering, for instance, that we have made only incremental improvements in prematurity and infant mortality, and that the age-old maternal problem of preeclampsia is still with us. We also face new challenges, such as the rising rate of maternal obesity and diabetes, which threaten both maternal and fetal health.
President Kennedy spoke of having “examined where we are strong, and where we are not.” Such self-reflection and assessment is a critical underpinning of advancement in fields across all of science, medicine, and health care, and in our specialty, it is a process that has driven ambitious new research efforts to improve fetal and maternal health.
A step back to more in-depth fundamental research on the biomolecular mechanisms of premature labor and diabetes-associated birth defects, for instance, as well as new efforts to approach fetal surgery less invasively, are positioning us to both conquer our disappointments and achieve ambitious new moonshots.
The fetus as our patient
Fifty years ago, in 1966, a seminal paper in the Lancet reported that amniotic fluid cells could be cultured and were suitable for karyotyping (1[7434]:383-5). The tapping and examination of amniotic fluid had been reported on sporadically for many decades, for various clinical purposes, but by and large the fetal compartment was not invaded or directly examined. The fetus was instead the hopeful beneficiary of pregnancy care that focused on the mother. Fetal outcome was clouded in mystery, known only at birth.
With the Lancet report, prenatal detection of chromosomal disorders began to feel achievable, and the 1960s marked the beginning of a journey first through invasive methods of prenatal diagnosis and then through increasingly non-invasive approaches.
In 1970, just several years after the report on chromosome analysis of amniotic-fluid cells, another landmark paper in the New England Journal of Medicine described 162 amniocenteses performed between the 13th and 18th weeks of gestation and the detection of 10 cases of Down syndrome, as well as a few other cases of metabolic and other disorders (282[11]:596-9). This report provided an impetus for broader use of the procedure to detect neural tube defects, Down syndrome, and other abnormalities.
The adoption of amniocentesis for prenatal diagnosis still took some time, however. The procedure was used primarily early on to determine fetal lung maturity, and to predict the ability of the fetus to survive after delivery.
At the time, it was widely praised as an advanced method for evaluating the fetus. Yet, looking back, the early years of the procedure seem primitive. The procedure was done late in pregnancy and it was performed blindly, with the puncture site located either with external palpation of the uterus or with the assistance of static ultrasound. Patients who had scans would usually visit the radiologist, who would mark on the patient’s abdomen a suggested location for needle insertion. Upon the patient’s return, the obstetrician would then insert a needle into that spot, blindly and likely after the fetus had moved.
The development and adoption of real-time ultrasound was a revolutionary achievement. Ultrasound-guided amniocentesis was first described in 1972, 14 years after Ian Donald’s seminal paper introducing obstetric ultrasound was published in the Lancet (1958 Jun 7;1[7032]:1188-95).
As real-time ultrasound made its way into practice, it marked the true realization of a moonshot for obstetrics.
Not only could we simultaneously visualize the needle tip and place the needle safety, but we could see the real-time movement of the fetus, its activity, and the surrounding pockets of fluid. It was like looking up into the sky and seeing the stars for the first time. We could see fetal arrhythmia – not only hear it. With this window into the fetal compartment, we could visualize the fetal bowel migrating into the chest cavity due to a hole (hernia) in the diaphragm. We could visualize other malformations as well.
Chorionic villus sampling (CVS) was technically more difficult and took longer to evolve. For years, through the early 1980s, it was performed only at select centers throughout the country. Patients traveled for the procedure and faced relatively significant risks of complications.
By the end of the 1980s, however, with successive improvements in equipment and technique (including development of a transabdominal approach in addition to transvaginal) the procedure was deemed safe, effective, and acceptable for routine use. Fetoscopy, pioneered by John Hobbins, MD, and his colleagues at Yale University, New Haven, Conn., had also advanced and was being used to diagnose sickle cell anemia, Tay-Sachs disease, congenital fetal skin diseases, and other disorders.
With these advances and with our newfound ability to obtain and analyze a tissue sample earlier in pregnancy – even before a woman shared the news of her pregnancy, in some cases – it seemed that we had achieved our goals and may have even reached past the moon.
Yet there were other moonshots being pursued, including initiatives to make prenatal diagnosis less invasive. The discovery in 1997 of cell-free fetal DNA in maternal plasma and serum, for instance, was a pivotal development that opened the door for noninvasive prenatal testing.
This, and other advances in areas from biochemistry to ultrasound to genomic analysis, led to an array of prenatal diagnostic tools that today enable women and their physicians to assess the genetic, chromosomal, and biophysical aspects of their fetus considerably before the time of viability, and from both the maternal side and directly in the fetal compartment.
First-trimester screening is a current option, and we now have the ability to more selectively perform amniocentesis and CVS based on probability testing, and not solely on maternal age. Ultrasound technology now encompasses color Doppler, 3D and 4D imaging, and other techniques that can be used to assess the placenta, various structures inside the brain, and the heart, as well as blood flow through the ductus venosus.
Parents have called for and welcomed having the option of assessing the fetus in greater detail, and of having either assurance when anomalies are excluded or the opportunity to plan and make decisions when anomalies are detected.
Fetal surgery has been a natural extension of our unprecedented access to the fetus. Our ability to visualize malformations and their evolution led to animal studies that advanced our interest in arresting, correcting, or reversing fetal anomalies through in-utero interventions. In 1981, surgeons performed the first human open fetal surgery to correct congenital hydronephrosis.
Today, we can employ endoscopic laser ablation or laser coagulation to treat severe twin-to-twin syndrome, for instance, as well as other surgical techniques to repair defects such as congenital diaphragmatic hernia, lower urinary tract obstruction, and myelomeningocele. Such advances were unimaginable decades ago.
Old foes and new threats
Despite these advances in diagnosis and care, obstetrics faces unrealized moonshots – lingering challenges that, 50 years ago, we would have predicted would have been solved. Who would have thought that we would still have as high an infant mortality rate as we do, and that we would not be further along in solving the problem of prematurity? Our progress has been only incremental.
Fifty years ago, we lacked an understanding of the basic biology of preterm labor. Prematurity was viewed simply as term labor occurring too early, and many efforts were made over the years to halt the premature labor process through the use of various drugs and other therapeutics, with variable and minimally impactful levels of success.
In the last 25 years, and especially in the last decade, we have made greater efforts to better understand the biology of premature labor – to elucidate how and why it occurs – and we have come to understand that premature labor is very different physiologically from term labor.
Thanks to the work at the Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), led by Roberto Romero, MD, attention has consequently shifted toward prediction, identification of women at highest risk, and prevention of the onset of premature labor among those deemed to be at highest risk.
Cervical length in the mid-trimester is now a well-verified predictor of preterm birth, and vaginal progesterone has been shown to benefit women without other known risk factors who are diagnosed with a shortened cervical length.
We have consequently seen the preterm birth rate decline a bit. In 2013, the last year for which we have complete data, the preterm birth rate dropped to 11.4%, down from a high of 12.8% in 2006, according to the Centers for Disease Control and Prevention.
Infant mortality similarly remains unacceptably high, due largely to the high preterm birth rate and to our failure to significantly alter the prevalence of birth defects. In 2010, according to the CDC, the infant mortality rate in the U.S. was 6.1 deaths per 1,000 live births (compared with 6.87 in 2005), and the United States ranked 26th in infant mortality among countries belonging to the Organisation for Economic Co-operation and Development, despite the fact that we spend a significant portion of our gross domestic product (17.5% in 2014) on health care.
Birth defects have taken over as a leading cause of infant mortality after early newborn life, and while we’ve made some advancements in understanding and diagnosing them, the majority of causes of birth defects are still unknown.
On the maternal side of obstetrical care, our progress has similarly been more modest than we have hoped for. Preeclampsia remains a problem, for instance. Despite decades of research into its pathogenesis, our advancements have been only incremental, and the condition – particularly its severe form – continues to be a vexing and high-risk problem.
Added to such age-old foes, moreover, are the growing threats of maternal obesity and diabetes, two closely related and often chronic conditions that affect not only the health of the mother but the in-utero environment and the health of the fetus. Today, more than one-third of all adults in the U.S., and 34% of women aged 20-39 years, are obese, and almost 10% of the U.S. population has diabetes.
Both conditions are on the rise, and obstetrics is confronting an epidemic of “diabesity” that would not necessarily have been predicted 50 years ago. It is particularly alarming given our growing knowledge of how obesity can be programmed in-utero and essentially passed on from generation to generation, of how diabetes can negatively affect perinatal outcomes, and of how the two conditions can have an additive effect on fetal complications.
Achieving new moonshots
Concerted efforts in the past several decades to step back and try to understand the basic biology and physiology of term labor and of premature labor have better positioned our specialty to achieve the moonshot of significantly reducing the incidence of preterm birth.
Establishment in the mid-1980s of the NICHD’s Perinatology Research Branch was a major development in this regard, helping to build and direct research efforts, including basic laboratory science, toward questions about what triggers and propagates labor. There has been notable progress in the past decade, in particular, and our specialty is now on the right path toward development of therapeutic interventions for preventing prematurity.
Additionally, the NICHD’s recently launched Human Placenta Project is building upon the branch-sponsored animal and cell culture model systems of the placenta to allow researchers, for the first time, to monitor human placental health in real time. By more fully understanding the role of the placenta in health and disease, we will be able to better evaluate pregnancy risks and improve pregnancy outcomes.
We also are learning through research in the University of Maryland Birth Defects Research Laboratory, which I am privileged to direct, and at other facilities, that maternal hyperglycemia is a teratogen, creating insults that can trigger a series of developmental fetal defects. By studying the biomolecular mechanisms of hyperglycemia-induced birth defects and developing “molecular maps,” we expect to be able to develop strategies for preventing or mitigating the development of such anomalies. I hope and expect that these future advancements, combined with reductions in prematurity, will significantly impact the infant mortality rate.
Fetal therapy and surgery will also continue to advance, with a much more minimally invasive approach taken in the next 50 years to addressing the fetal condition without putting the mother at increased risk. Just as surgery in other fields has moved from open laparotomy to minimally invasive techniques, I believe we will develop endoscopic or laparoscopic means of correcting the various problems in-utero, such as the repair of neural tube defects and diaphragmatic hernias. It already appears likely that a fetoscopic approach to treating myelomeningocele can reduce maternal morbidity while achieving infant neurological outcomes that are at least as good as outcomes achieved with open fetal surgery.
We’re in a much different position than we were 50 years ago in that we have two patients – the mother and the fetus – with whom we can closely work. We also have a relatively new and urgent obligation to place our attention not only on women’s reproductive health, but on the general gynecologic state. Ob.gyns. often are the only primary care physicians whom women see for routine care, and the quality of our attention to their weight and their diabetes risk factors will have far-reaching consequences, both for them and for their offspring.
As we have since the 1960s, we will continue to set new moonshots and meet new challenges, working with each other and with our patients to evaluate where we are strong and where we must improve. We will persistently harness the power of technology, choosing to do the things that “are hard,” while stepping back as needed to ask and address fundamental questions.
As a result, I can envision the next 50 years as a revolutionary time period for obstetrics – a time in which current problems and disorders are abated or eliminated through a combination of genomics, microbiomics, and other technological advances. Someday in the future, we will look back on some of our many achievements and marvel at how we have transformed the unimaginable to reality.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Select advances through the years
1960s
1965: Siemens Corp. introduces first real-time ultrasound scanner.
1966: Lancet paper reports that amniotic fluid cells can be cultured and karyotyped.
1970s
1970: New England Journal of Medicine paper describes mid-trimester amniocenteses and detection of Down syndrome cases.
1972: Ultrasound-guided amniocentesis first described.
1973: Fetoscopy introduced.
1980s
1981: First human open fetal surgery to correct congenital hydronephrosis.
Early 1980s: Chorionic villus sampling introduced at select centers.
1985: Color Doppler incorporated into ultrasound.
1990s
1990: Embryoscopy first described.
Mid-1990s: 3D/4D ultrasound begins to assume major role in ob.gyn. imaging.1997: Discovery of cell-free fetal DNA in maternal plasma.
2000s
2003: MOMS (Management of Myelomeningocele Study) was launched.
2010s
2012: The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support cell-free DNA screening for women at increased risk of fetal aneuploidy.
2013: Preterm birth rate drops to 11.4%
2014: Diabetes incidence marks a 4-fold increase since 1980.
In 1961 before Congress, and in 1962 at Rice University, Houston, President John F. Kennedy called on America to land a man on the moon and bring him back safely, and to look beyond the moon as well, and pursue an ambitious space exploration program. He challenged the country to think and act boldly, telling Americans in his speech at Rice that “we choose to go the moon in this decade and do the other things, not because they are easy, but because they are hard.”
When Neil Armstrong and Buzz Aldrin set foot on the moon in 1969 – even before President Kennedy’s 10-year deadline had arrived – the country’s primary moonshot was realized. The President had inspired the nation, teams of engineers and others had collectively met daunting technological challenges, and space consequently was more open to us than ever before.
In looking at the field of obstetrics and how far it has come in the past 50 years, since the 1960s, it is similarly astonishing and inspiring to reflect on what extraordinary advances we have made. Who would have thought that the fetus would become such a visible and intimate patient – one who, like the mother, can be interrogated, monitored, and sometimes treated before birth? Who would have thought we would be utilizing genomic studies in a now well-established field of prenatal diagnosis, or that fetal therapy would become a field in and of itself?
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Our specialty has advanced through a series of moonshots that have been inspired and driven by technological advancement and by our continually bold goals and vision for the health and well-being of women and their offspring. We have taken on ambitious challenges, achieved many goals, and embraced advancements in practice only to then set new targets that previously were unimaginable.
Yet just as our country’s space exploration program has faced disappointments, so has our field. It is sobering, for instance, that we have made only incremental improvements in prematurity and infant mortality, and that the age-old maternal problem of preeclampsia is still with us. We also face new challenges, such as the rising rate of maternal obesity and diabetes, which threaten both maternal and fetal health.
President Kennedy spoke of having “examined where we are strong, and where we are not.” Such self-reflection and assessment is a critical underpinning of advancement in fields across all of science, medicine, and health care, and in our specialty, it is a process that has driven ambitious new research efforts to improve fetal and maternal health.
A step back to more in-depth fundamental research on the biomolecular mechanisms of premature labor and diabetes-associated birth defects, for instance, as well as new efforts to approach fetal surgery less invasively, are positioning us to both conquer our disappointments and achieve ambitious new moonshots.
The fetus as our patient
Fifty years ago, in 1966, a seminal paper in the Lancet reported that amniotic fluid cells could be cultured and were suitable for karyotyping (1[7434]:383-5). The tapping and examination of amniotic fluid had been reported on sporadically for many decades, for various clinical purposes, but by and large the fetal compartment was not invaded or directly examined. The fetus was instead the hopeful beneficiary of pregnancy care that focused on the mother. Fetal outcome was clouded in mystery, known only at birth.
With the Lancet report, prenatal detection of chromosomal disorders began to feel achievable, and the 1960s marked the beginning of a journey first through invasive methods of prenatal diagnosis and then through increasingly non-invasive approaches.
In 1970, just several years after the report on chromosome analysis of amniotic-fluid cells, another landmark paper in the New England Journal of Medicine described 162 amniocenteses performed between the 13th and 18th weeks of gestation and the detection of 10 cases of Down syndrome, as well as a few other cases of metabolic and other disorders (282[11]:596-9). This report provided an impetus for broader use of the procedure to detect neural tube defects, Down syndrome, and other abnormalities.
The adoption of amniocentesis for prenatal diagnosis still took some time, however. The procedure was used primarily early on to determine fetal lung maturity, and to predict the ability of the fetus to survive after delivery.
At the time, it was widely praised as an advanced method for evaluating the fetus. Yet, looking back, the early years of the procedure seem primitive. The procedure was done late in pregnancy and it was performed blindly, with the puncture site located either with external palpation of the uterus or with the assistance of static ultrasound. Patients who had scans would usually visit the radiologist, who would mark on the patient’s abdomen a suggested location for needle insertion. Upon the patient’s return, the obstetrician would then insert a needle into that spot, blindly and likely after the fetus had moved.
The development and adoption of real-time ultrasound was a revolutionary achievement. Ultrasound-guided amniocentesis was first described in 1972, 14 years after Ian Donald’s seminal paper introducing obstetric ultrasound was published in the Lancet (1958 Jun 7;1[7032]:1188-95).
As real-time ultrasound made its way into practice, it marked the true realization of a moonshot for obstetrics.
Not only could we simultaneously visualize the needle tip and place the needle safety, but we could see the real-time movement of the fetus, its activity, and the surrounding pockets of fluid. It was like looking up into the sky and seeing the stars for the first time. We could see fetal arrhythmia – not only hear it. With this window into the fetal compartment, we could visualize the fetal bowel migrating into the chest cavity due to a hole (hernia) in the diaphragm. We could visualize other malformations as well.
Chorionic villus sampling (CVS) was technically more difficult and took longer to evolve. For years, through the early 1980s, it was performed only at select centers throughout the country. Patients traveled for the procedure and faced relatively significant risks of complications.
By the end of the 1980s, however, with successive improvements in equipment and technique (including development of a transabdominal approach in addition to transvaginal) the procedure was deemed safe, effective, and acceptable for routine use. Fetoscopy, pioneered by John Hobbins, MD, and his colleagues at Yale University, New Haven, Conn., had also advanced and was being used to diagnose sickle cell anemia, Tay-Sachs disease, congenital fetal skin diseases, and other disorders.
With these advances and with our newfound ability to obtain and analyze a tissue sample earlier in pregnancy – even before a woman shared the news of her pregnancy, in some cases – it seemed that we had achieved our goals and may have even reached past the moon.
Yet there were other moonshots being pursued, including initiatives to make prenatal diagnosis less invasive. The discovery in 1997 of cell-free fetal DNA in maternal plasma and serum, for instance, was a pivotal development that opened the door for noninvasive prenatal testing.
This, and other advances in areas from biochemistry to ultrasound to genomic analysis, led to an array of prenatal diagnostic tools that today enable women and their physicians to assess the genetic, chromosomal, and biophysical aspects of their fetus considerably before the time of viability, and from both the maternal side and directly in the fetal compartment.
First-trimester screening is a current option, and we now have the ability to more selectively perform amniocentesis and CVS based on probability testing, and not solely on maternal age. Ultrasound technology now encompasses color Doppler, 3D and 4D imaging, and other techniques that can be used to assess the placenta, various structures inside the brain, and the heart, as well as blood flow through the ductus venosus.
Parents have called for and welcomed having the option of assessing the fetus in greater detail, and of having either assurance when anomalies are excluded or the opportunity to plan and make decisions when anomalies are detected.
Fetal surgery has been a natural extension of our unprecedented access to the fetus. Our ability to visualize malformations and their evolution led to animal studies that advanced our interest in arresting, correcting, or reversing fetal anomalies through in-utero interventions. In 1981, surgeons performed the first human open fetal surgery to correct congenital hydronephrosis.
Today, we can employ endoscopic laser ablation or laser coagulation to treat severe twin-to-twin syndrome, for instance, as well as other surgical techniques to repair defects such as congenital diaphragmatic hernia, lower urinary tract obstruction, and myelomeningocele. Such advances were unimaginable decades ago.
Old foes and new threats
Despite these advances in diagnosis and care, obstetrics faces unrealized moonshots – lingering challenges that, 50 years ago, we would have predicted would have been solved. Who would have thought that we would still have as high an infant mortality rate as we do, and that we would not be further along in solving the problem of prematurity? Our progress has been only incremental.
Fifty years ago, we lacked an understanding of the basic biology of preterm labor. Prematurity was viewed simply as term labor occurring too early, and many efforts were made over the years to halt the premature labor process through the use of various drugs and other therapeutics, with variable and minimally impactful levels of success.
In the last 25 years, and especially in the last decade, we have made greater efforts to better understand the biology of premature labor – to elucidate how and why it occurs – and we have come to understand that premature labor is very different physiologically from term labor.
Thanks to the work at the Perinatology Research Branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), led by Roberto Romero, MD, attention has consequently shifted toward prediction, identification of women at highest risk, and prevention of the onset of premature labor among those deemed to be at highest risk.
Cervical length in the mid-trimester is now a well-verified predictor of preterm birth, and vaginal progesterone has been shown to benefit women without other known risk factors who are diagnosed with a shortened cervical length.
We have consequently seen the preterm birth rate decline a bit. In 2013, the last year for which we have complete data, the preterm birth rate dropped to 11.4%, down from a high of 12.8% in 2006, according to the Centers for Disease Control and Prevention.
Infant mortality similarly remains unacceptably high, due largely to the high preterm birth rate and to our failure to significantly alter the prevalence of birth defects. In 2010, according to the CDC, the infant mortality rate in the U.S. was 6.1 deaths per 1,000 live births (compared with 6.87 in 2005), and the United States ranked 26th in infant mortality among countries belonging to the Organisation for Economic Co-operation and Development, despite the fact that we spend a significant portion of our gross domestic product (17.5% in 2014) on health care.
Birth defects have taken over as a leading cause of infant mortality after early newborn life, and while we’ve made some advancements in understanding and diagnosing them, the majority of causes of birth defects are still unknown.
On the maternal side of obstetrical care, our progress has similarly been more modest than we have hoped for. Preeclampsia remains a problem, for instance. Despite decades of research into its pathogenesis, our advancements have been only incremental, and the condition – particularly its severe form – continues to be a vexing and high-risk problem.
Added to such age-old foes, moreover, are the growing threats of maternal obesity and diabetes, two closely related and often chronic conditions that affect not only the health of the mother but the in-utero environment and the health of the fetus. Today, more than one-third of all adults in the U.S., and 34% of women aged 20-39 years, are obese, and almost 10% of the U.S. population has diabetes.
Both conditions are on the rise, and obstetrics is confronting an epidemic of “diabesity” that would not necessarily have been predicted 50 years ago. It is particularly alarming given our growing knowledge of how obesity can be programmed in-utero and essentially passed on from generation to generation, of how diabetes can negatively affect perinatal outcomes, and of how the two conditions can have an additive effect on fetal complications.
Achieving new moonshots
Concerted efforts in the past several decades to step back and try to understand the basic biology and physiology of term labor and of premature labor have better positioned our specialty to achieve the moonshot of significantly reducing the incidence of preterm birth.
Establishment in the mid-1980s of the NICHD’s Perinatology Research Branch was a major development in this regard, helping to build and direct research efforts, including basic laboratory science, toward questions about what triggers and propagates labor. There has been notable progress in the past decade, in particular, and our specialty is now on the right path toward development of therapeutic interventions for preventing prematurity.
Additionally, the NICHD’s recently launched Human Placenta Project is building upon the branch-sponsored animal and cell culture model systems of the placenta to allow researchers, for the first time, to monitor human placental health in real time. By more fully understanding the role of the placenta in health and disease, we will be able to better evaluate pregnancy risks and improve pregnancy outcomes.
We also are learning through research in the University of Maryland Birth Defects Research Laboratory, which I am privileged to direct, and at other facilities, that maternal hyperglycemia is a teratogen, creating insults that can trigger a series of developmental fetal defects. By studying the biomolecular mechanisms of hyperglycemia-induced birth defects and developing “molecular maps,” we expect to be able to develop strategies for preventing or mitigating the development of such anomalies. I hope and expect that these future advancements, combined with reductions in prematurity, will significantly impact the infant mortality rate.
Fetal therapy and surgery will also continue to advance, with a much more minimally invasive approach taken in the next 50 years to addressing the fetal condition without putting the mother at increased risk. Just as surgery in other fields has moved from open laparotomy to minimally invasive techniques, I believe we will develop endoscopic or laparoscopic means of correcting the various problems in-utero, such as the repair of neural tube defects and diaphragmatic hernias. It already appears likely that a fetoscopic approach to treating myelomeningocele can reduce maternal morbidity while achieving infant neurological outcomes that are at least as good as outcomes achieved with open fetal surgery.
We’re in a much different position than we were 50 years ago in that we have two patients – the mother and the fetus – with whom we can closely work. We also have a relatively new and urgent obligation to place our attention not only on women’s reproductive health, but on the general gynecologic state. Ob.gyns. often are the only primary care physicians whom women see for routine care, and the quality of our attention to their weight and their diabetes risk factors will have far-reaching consequences, both for them and for their offspring.
As we have since the 1960s, we will continue to set new moonshots and meet new challenges, working with each other and with our patients to evaluate where we are strong and where we must improve. We will persistently harness the power of technology, choosing to do the things that “are hard,” while stepping back as needed to ask and address fundamental questions.
As a result, I can envision the next 50 years as a revolutionary time period for obstetrics – a time in which current problems and disorders are abated or eliminated through a combination of genomics, microbiomics, and other technological advances. Someday in the future, we will look back on some of our many achievements and marvel at how we have transformed the unimaginable to reality.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Select advances through the years
1960s
1965: Siemens Corp. introduces first real-time ultrasound scanner.
1966: Lancet paper reports that amniotic fluid cells can be cultured and karyotyped.
1970s
1970: New England Journal of Medicine paper describes mid-trimester amniocenteses and detection of Down syndrome cases.
1972: Ultrasound-guided amniocentesis first described.
1973: Fetoscopy introduced.
1980s
1981: First human open fetal surgery to correct congenital hydronephrosis.
Early 1980s: Chorionic villus sampling introduced at select centers.
1985: Color Doppler incorporated into ultrasound.
1990s
1990: Embryoscopy first described.
Mid-1990s: 3D/4D ultrasound begins to assume major role in ob.gyn. imaging.1997: Discovery of cell-free fetal DNA in maternal plasma.
2000s
2003: MOMS (Management of Myelomeningocele Study) was launched.
2010s
2012: The American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine support cell-free DNA screening for women at increased risk of fetal aneuploidy.
2013: Preterm birth rate drops to 11.4%
2014: Diabetes incidence marks a 4-fold increase since 1980.
Zika virus challenges ob.gyn. practice
Viral illnesses in pregnancy are not unheard of. When a patient presents with symptoms, we often think of an influenza type of infection that will be cleared within a short period of time and with few negative consequences for the developing fetus. Other infections that can occur include TORCH – Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes – infections, but these are also relatively common.
Rarely do we in the United States consider a gravida’s vulnerability to tropical infectious diseases such as dengue, chikungunya, and now Zika virus. With the popularity and ease of international travel, and the potential for women’s exposure to more exotic diseases, the practice of ob.gyn. must undergo a significant transition in perspective. It is vital for us to understand these illnesses because of their potency and reported injury to both the mother and baby, for several reasons.
First, there is the public health concern. As of June 16, 2016, the Pan American Health Organization of the World Health Organization, reported 39 countries and territories in the Americas with confirmed cases of Zika virus, with 21 of those countries having confirmed cases in pregnant women.
As of June 9, 2016, the Centers for Disease Control and Prevention reported that 234 pregnant women in the United States have laboratory evidence of possible Zika infection, along with 189 pregnant women living in U.S. territories. Since the current outbreak, which began in July 2015 in Brazil, seven countries – accounting for more than 1,600 cases – have reported babies with congenital syndrome associated with Zika virus, the majority of which have been in Brazil. With the Summer Olympics in Rio starting in August 2016, the potential spread of Zika virus is dizzying.
Second, there is the counseling and management concern. Without a treatment or vaccine available, ob.gyns. must stay current on the latest research and findings to inform their patients of the risks associated with travel to an area with confirmed, or areas at risk for developing, Zika virus transmission.
Third, there is a diagnostic concern. Women who have visited areas with Zika virus, or who have had intimate contact with someone who has traveled to these areas, must be diagnosed and then counseled immediately.
We have devoted this Master Class to a discussion of Zika virus and the work being conducted in the United States to understand this disease. We have invited Dr. Yoel Sadovsky, an expert on placental development and trophoblast function, and his colleague, Carolyn Coyne, Ph.D., a leading researcher on host-virus interactions, to address this important topic.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Viral illnesses in pregnancy are not unheard of. When a patient presents with symptoms, we often think of an influenza type of infection that will be cleared within a short period of time and with few negative consequences for the developing fetus. Other infections that can occur include TORCH – Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes – infections, but these are also relatively common.
Rarely do we in the United States consider a gravida’s vulnerability to tropical infectious diseases such as dengue, chikungunya, and now Zika virus. With the popularity and ease of international travel, and the potential for women’s exposure to more exotic diseases, the practice of ob.gyn. must undergo a significant transition in perspective. It is vital for us to understand these illnesses because of their potency and reported injury to both the mother and baby, for several reasons.
First, there is the public health concern. As of June 16, 2016, the Pan American Health Organization of the World Health Organization, reported 39 countries and territories in the Americas with confirmed cases of Zika virus, with 21 of those countries having confirmed cases in pregnant women.
As of June 9, 2016, the Centers for Disease Control and Prevention reported that 234 pregnant women in the United States have laboratory evidence of possible Zika infection, along with 189 pregnant women living in U.S. territories. Since the current outbreak, which began in July 2015 in Brazil, seven countries – accounting for more than 1,600 cases – have reported babies with congenital syndrome associated with Zika virus, the majority of which have been in Brazil. With the Summer Olympics in Rio starting in August 2016, the potential spread of Zika virus is dizzying.
Second, there is the counseling and management concern. Without a treatment or vaccine available, ob.gyns. must stay current on the latest research and findings to inform their patients of the risks associated with travel to an area with confirmed, or areas at risk for developing, Zika virus transmission.
Third, there is a diagnostic concern. Women who have visited areas with Zika virus, or who have had intimate contact with someone who has traveled to these areas, must be diagnosed and then counseled immediately.
We have devoted this Master Class to a discussion of Zika virus and the work being conducted in the United States to understand this disease. We have invited Dr. Yoel Sadovsky, an expert on placental development and trophoblast function, and his colleague, Carolyn Coyne, Ph.D., a leading researcher on host-virus interactions, to address this important topic.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
Viral illnesses in pregnancy are not unheard of. When a patient presents with symptoms, we often think of an influenza type of infection that will be cleared within a short period of time and with few negative consequences for the developing fetus. Other infections that can occur include TORCH – Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes – infections, but these are also relatively common.
Rarely do we in the United States consider a gravida’s vulnerability to tropical infectious diseases such as dengue, chikungunya, and now Zika virus. With the popularity and ease of international travel, and the potential for women’s exposure to more exotic diseases, the practice of ob.gyn. must undergo a significant transition in perspective. It is vital for us to understand these illnesses because of their potency and reported injury to both the mother and baby, for several reasons.
First, there is the public health concern. As of June 16, 2016, the Pan American Health Organization of the World Health Organization, reported 39 countries and territories in the Americas with confirmed cases of Zika virus, with 21 of those countries having confirmed cases in pregnant women.
As of June 9, 2016, the Centers for Disease Control and Prevention reported that 234 pregnant women in the United States have laboratory evidence of possible Zika infection, along with 189 pregnant women living in U.S. territories. Since the current outbreak, which began in July 2015 in Brazil, seven countries – accounting for more than 1,600 cases – have reported babies with congenital syndrome associated with Zika virus, the majority of which have been in Brazil. With the Summer Olympics in Rio starting in August 2016, the potential spread of Zika virus is dizzying.
Second, there is the counseling and management concern. Without a treatment or vaccine available, ob.gyns. must stay current on the latest research and findings to inform their patients of the risks associated with travel to an area with confirmed, or areas at risk for developing, Zika virus transmission.
Third, there is a diagnostic concern. Women who have visited areas with Zika virus, or who have had intimate contact with someone who has traveled to these areas, must be diagnosed and then counseled immediately.
We have devoted this Master Class to a discussion of Zika virus and the work being conducted in the United States to understand this disease. We have invited Dr. Yoel Sadovsky, an expert on placental development and trophoblast function, and his colleague, Carolyn Coyne, Ph.D., a leading researcher on host-virus interactions, to address this important topic.
Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at [email protected].
