Giants in Obstetrics and Gynecology Series: a profile of Stuart Campbell, DSc, FRCPEd, FRCOG, FACOG

Dr Stuart Campbell, Emeritus Professor of Obstetrics and Gynecology at King’s College London in the United Kingdom, revolutionized obstetrics and gynecology through his seminal contributions in ultrasound imaging. Dr Campbell’s vision, talent, and inspired leadership are at the heart of these important advances in women’s health.

Dr Campbell introduced the use of fetal biometry to date pregnancy, initiated longitudinal studies of fetal growth, made the first prenatal diagnosis of anencephaly with ultrasound, and pioneered the use of uterine artery Doppler velocimetry to predict adverse pregnancy outcome. In gynecology, he has played a key role in the development of screening for ovarian cancer by combining imaging and biomarkers. He remains actively engaged in the use of imaging to optimize reproductive outcome in patients undergoing in vitro fertilization (IVF).

The department under Dr Campbell’s direction at King’s College trained a generation of leaders, and his power of convocation made possible the founding of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG). He is the founding Editor in Chief of Ultrasound in Obstetrics and Gynecology and recipient of the Ian Donald Gold Medal for excellence in ultrasound research in our discipline.

Dr Campbell is herein recognized as a “Giant in Obstetrics and Gynecology” for his many groundbreaking contributions to obstetrics and gynecology that have improved the lives of women and their families and for the lasting impact he has had on our discipline.

Early life, medicine, and obstetrics and gynecology

Stuart was born in Glasgow, Scotland, in 1936. His father, a businessman, served as a soldier after the Great Depression, and his mother, a nurse and “matron” (a hands-on director of nursing), instilled her medical interests in Stuart and his older brother, David (Figure 1). When Stuart was three years old, the family moved to Inveraray on Scotland’s western coast for safety during World War II, and he grew up in the small port town as a self-professed “country boy.” The family eventually returned inland to care for Stuart’s grandparents, settling in Paisley, a large town outside of Glasgow known for its production of textiles woven in the paisley pattern. Stuart commuted by train to attend the University of Glasgow Medical School. His field of study was influenced not only by his mother but also his brother, who had become a physician and passed down his medical textbooks to Stuart.

Figure 1.

The Campbell family in 1936.

Left to right: grandfather David holding Stuart’s brother David, father David (standing), mother Mary Ann holding 3-month-old Stuart. “David” is the Campbell family name for firstborn males, a tradition that dates back to at least the 19th century.

Photo courtesy of Dr. Campbell.

When I asked Stuart why he decided to go into medicine, he acknowledged that he did not receive the “call” to medicine at the start. When asked by an interviewer at the medical school why he wished to be a doctor, Stuart quipped, “I didn’t hear the voice in the night, if that’s what you mean,” much to the interviewer’s amusement. Yet, when Stuart began his clinical rotations, he found excitement in the delivery room, distinguished himself in obstetrics and gynecology during his final examinations, and then decided to pursue the field. After graduating in 1961, Stuart took a position as a junior physician with Dr Ian Donald at the Queen Mother’s Hospital in Glasgow. Stuart noted that he became serious about medicine when he “suddenly realized that people depended on me.”

Use of biparietal diameter to date pregnancy

Stuart spent the early part of his career with Dr Donald, a British obstetrician and Regius Chair of Midwifery at the University of Glasgow, who built the first ultrasound machine in collaboration with engineer Thomas Brown. Dr Donald introduced Stuart to the basic principles of ultrasound and the application of this tool to clinical medicine, such as diagnosing the hydatidiform mole.

During this time, Stuart became aware of the need to develop a standardized method to measure the biparietal diameter (known then as fetal cephalometry). The ultrasonographic technique in use, which applied the one-dimensional amplitude mode (A-mode) to measure this fetal parameter, had limitations: it was often difficult to locate the fetal head in early pregnancy, and measurements were not reproducible. “I thought that by requiring the landmark of a midline echo the measurement of the biparietal diameter would become more reproducible and accurate,” he said.

The issue of standardizing the plane to measure the biparietal diameter kept him awake at night. “I puzzled over how to angle the ultrasound transducer to capture the optimal axial plane of the fetal head and how to balance the echoes correctly to get a midline echo,” he recalled. “I eventually worked it out and developed a precise technique of measuring the biparietal diameter of the fetal head by combining the amplitude mode and bright mode methods” (Figure 2). To determine the orientation of the fetal head, Stuart first used the brightness mode (B-mode) to visualize the midline echo of the fetal brain on a two-dimensional display. He then performed A-mode scans to measure the distance between the two parietal bones (A-mode was required because the placement of calipers on the B-mode image was imprecise). The 1968 groundbreaking study described this combined approach, a method quickly adopted as the standard practice in obstetric ultrasound examination for the next decade^1,2 (Figure 3).

Figure 2.

Combined brightness (B-mode) and amplitude (A-mode) measurement of the biparietal diameter, 1969³

Campbell’s method of measuring the biparietal diameter at 20 weeks (menstrual age): Left: B-mode scan is first used to obtain a true transverse section of the fetal head with the midline echo bisecting (blue arrow). Right: A-mode scan depicts the cranial echoes (red arrows) and midline echo (blue arrow) allowing precise measurement across the parietal diameter.

Photo courtesy of Dr Campbell.

Figure 3.

1968 study on fetal cephalometry by ultrasound.

The biparietal diameter became, and still is, the most commonly used fetal biometric parameter to assess gestational age worldwide. In another landmark study in 1969, Stuart reported that early measurement of the biparietal diameter gave an equivalent (or better) estimate of gestational age in pregnancies with an unknown date or a date/size discrepancy compared to those with a certain date.³ In a later study based on a large technician-based routine ultrasound program, he found that biparietal diameter measurements performed between 12 and 18 weeks of gestation were significantly more accurate in gestational-age predictions (89.4%) than those based on optimal menstrual history (84.7%) or crown-rump length measurement (84.6%) (all P<.001).⁴ The study concluded that a single ultrasound scan of the biparietal diameter performed before 18 weeks of gestation was the single-best dating parameter, thus justifying a routine scan in all pregnancies. Moreover, Stuart’s finding established scanning at 16 to 18 weeks of gestation as the optimal time for studying fetal morphology, which became standard practice in his department.

Solving the problem of assigning gestational age was one of the most important contributions to obstetrics by Stuart during the 20th century. Gestational age established along with fetal size had important benefits: a decrease in inductions of inaccurately diagnosed postterm gestations, the prevention of iatrogenic prematurity, and an accurate interpretation of biomarkers in maternal blood and amniotic fluid. Furthermore, this new, solid dimension of visualization improved the clinical management of pregnancy by freeing practitioners and patients from reliance on the first day of the last menstrual period as a parameter for gestational dating.

Stuart is the first obstetrician to advocate for routine scanning of all pregnancies to date gestational age. He insisted that fetal biometric parameters be obtained in a precise plane defined by anatomic landmarks: first, the biparietal diameter, followed by abdominal circumference, and then virtually all biometric parameters. His initiative has influenced clinical research and the practice of medicine.

Serial biometry to assess fetal growth: another first

Pediatricians have studied infant growth for decades. However, investigation of fetal growth was impossible given the dearth of safe imaging techniques to assess changes in fetal size throughout gestation. Stuart originated the scientific genre of fetal growth studies by describing changes in biparietal diameter that occur with advancing gestational age in the same fetus, generating the first estimates of fetal growth (velocity).^2,3,5

The longitudinal study of fetal growth generally began around 16 weeks of gestation, and Stuart obtained serial measurements every two to three weeks. His method allowed reporting of the first fetal growth velocity graphs. Stuart identified two distinct patterns of growth deceleration: (1) fetuses that were small from an early age and whose growth gradually fell below the reference range (ie, the “low profile growth pattern” associated with congenital abnormalities) and (2) fetuses of normal size whose growth declined later in pregnancy (ie, the “late flattening pattern” associated with fetal growth restriction)⁶ (Figure 4).

Figure 4.

Serial cephalometry: the first assessment of fetal growth restriction, 1970²

A representation of biparietal diameter measurements showing the accurate capture of the midline echoes from 13 weeks of gestation throughout the second trimester.

Photo courtesy of Dr Campbell.

From Glasgow to London

In 1968, Stuart applied for a position at the Institute of Obstetrics and Gynaecology at Queen Charlotte’s Maternity Hospital in London. No Scottish-born junior physician had ever been given a position there, and sure enough, Stuart received a letter politely declining his application. A few days later, however, he received a call from Dr Jack Dewhurst, who had just begun his tenure at the hospital and had made diversity of staff a priority. Speaking in a quiet voice, he told Stuart that he had read his curriculum vitae and then invited him to interview for the position. After Stuart met with Dr Dewhurst and Dr Richard Beard the next day, he received the job offer.

In 1973, Dr Juiry (Yuri) Wladimiroff joined Stuart’s team as his first research fellow at Queen Charlotte’s. “He worked with me on fetal urine production rates in the assessment of fetal wellbeing,” Stuart recalled. “After a year, he returned to Rotterdam to Erasmus University and ultimately became a leader in our field pioneering Doppler studies of the fetal circulation, particularly in the internal carotid artery. Yuri served on the Society’s first Executive Committee and is a Gold Medal winner.”

Fetal abdominal circumference to assess fetal weight and growth

Stuart was determined to develop a more accurate way of measuring fetal body size. A paper published by this Journal in 1965⁷ reported on the use of fetal chest circumference measurements in assessing fetal growth. However, given the conical shape of the fetal thorax, the results were not easily reproducible. Consequently, Stuart looked to the more cylindrically shaped fetal abdomen, focusing on the liver as the organ most affected by fetal growth restriction. He identified the plane where the umbilical vein meets the portal vein as an easily identifiable landmark to measure the abdominal circumference, thus increasing accuracy and reliability.

In 1975, Stuart reported a nomogram of fetal abdominal circumference vs birthweight in fetuses delivered within 48 hours of abdominal circumference measurement.⁸ That study showed the accuracy of predictions varied with the size of the fetus: at a predicted weight of 1 kg, 95% of birthweights fell within 160 g, whereas at 2 kg, 3 kg, and 4 kg, the corresponding values were 290 g, 450 g, and 590 g, respectively. He recommended abdominal circumference as the optimal parameter in screening for the small-for-gestational-age fetus, provided an early dating scan had been performed. Stuart would have been amused to know at that time that abdominal circumference would be the key parameter in predicting fetal macrosomia right into the next century. Two years later, he described the ratio of head circumference to abdominal circumference, observing that this ratio was abnormal in cases of asymmetric fetal growth restriction.⁹

By 1980, with the advent of real-time ultrasound, Stuart’s group in London began to measure fetal limb bones¹⁰ and described yet another significant parameter—fetal femur length to assess gestational age in the second trimester,¹¹ a factor that would also become a method to screen for fetal skeletal dysplasias.

The first prenatal diagnosis of a congenital anomaly with ultrasound: anencephaly

During his time in Glasgow, Stuart made good use of the Diasonograph, the large ultrasound scanning machine designed by Dr Donald and engineer Thomas Brown. Consequently, Stuart arranged to have one procured for Queen Charlotte’s Maternity Hospital, which allowed the team there to take a lead in the early diagnosis of fetal abnormalities by ultrasound, and established Queen Charlotte’s Maternity Hospital as being at the “cutting edge” in 1972 (Figure 5).

Figure 5.

Stuart in action in the early 1970s—Diasonograph at Queen Charlotte’s Maternity Hospital, London, United Kingdom.

Photo courtesy of Dr. Campbell.

Prenatal diagnosis of congenital abnormalities had not been a particular focus of Stuart’s research until he encountered a patient whose 17-week scan did not show the landmarks of the biparietal diameter. “I was certain it was a case of anencephaly,” he recalled. “I measured the patient for two successive weeks to confirm this diagnosis.” His acumen afforded the first early diagnosis of a congenital abnormality, and Stuart published this case report in The Lancet¹² (Figures 6 and 7).

Figure 6.

Anencephaly study in The Lancet, 1972.

Figure 7.

Image of the fetal trunk and base of the skull demonstrating an absence of cranial echoes to confirm the diagnosis of anencephaly

Ultrasonograms 17 weeks after ovulation: A, anencephalic fetus, with absence of normal cephalic echoes; B, normal fetus, showing a cephalic outline. B, bladder; CP, cephalic pole; Cx, cervix; FH, fetal head; FT, fetal trunk; SP, symphysis pubis; UM, umbilicus.

With permission from The Lancet. 1972;300:1226–7.

He subsequently emphasized the value of screening women who had previously delivered a child with neural tube defects, thus predicting the possibility of screening all women for anencephaly in early pregnancy. This contribution was the basis for what is now an essential component of prenatal care—screening for congenital anomalies during pregnancy. That initial case report led to a series of studies evaluating diagnostic methods for neural tube defects. Stuart collaborated with Dr Mary Seller of the Pediatric Research Unit at Guy’s Hospital, now Professor of Developmental Genetics at King’s College London, to compare the reliability of ultrasound examination and the estimation of alpha fetoprotein (AFP) levels in both amniotic fluid and maternal serum in diagnosing neural tube defects and spina bifida in particular. The ultrasound examination included not only fetal head assessment for anencephaly but also a detailed fetal spine examination, followed by a series of transverse scans to demonstrate the circular appearance of a spinal cord. Stuart and Dr Seller reported on three representative cases in The Lancet that revealed the important role of ultrasound examination in the prenatal assessment of spina bifida, including the first successful early diagnosis of spina bifida by ultrasound (Figure 8).¹³

Figure 8.

Early prenatal diagnosis of spina bifida at 18 weeks, 1975.

Left image: Transverse scan of normal spine showing circular spinal canal. Right image: Transverse scan of spine showing “U” shaped abnormality of spina bifida.

Photo courtesy of Dr Campbell.

Concurrently, the team also compared AFP levels in maternal serum between two groups of women: those whose fetus had severe neural tube defects (some taken from the prospective study) and a control group. They found increased concentrations of AFP in maternal serum samples collected in the cases with neural tube defects; however, this finding was not significantly different from the higher levels seen in the control group. Assessing levels of AFP in amniotic fluid provided a more clearly defined difference and was more reliable in diagnosing neural tube defects.¹⁴ However, by 1977, Stuart reported on 329 high-risk pregnancies examined at 16–20 weeks of gestation in which ultrasound identified 25 of 28 neural tube defects; 10 of 13 cases of spina bifida were detected, with low sacral lesions presenting as false negatives.¹⁵ He also found that examining AFP concentrations could not describe the location and precise nature of the neural tube defect, whereas ultrasound examination usually enabled this diagnosis, including associated ventriculomegaly.

Fetoscopy, fetal blood sampling, and the Harris Birthright Research Centre for Fetal Medicine

In 1976, Stuart was appointed Professor and Head of Obstetrics and Gynaecology at King’s College Hospital Medical School in London (Figure 9). “I was lucky to have as my lecturer then-Associate Professor Dr Charles Rodeck, who was carrying out studies on human placental lactogen,” Stuart reminisced. “Yet, he agreed to learn the technique of ultrasound-guided fetoscopy — an endoscopic procedure to visualize the fetus and vessels on the placental surface.”

Figure 9.

Stuart in his office at King’s College Hospital, overlooking Camberwell, United Kingdom.

Photo courtesy of Dr Campbell.

Stuart believed that this procedure, pioneered by Dr John Hobbins at Yale University, might well have great potential in prenatal diagnosis. He again acquired a Diasonograph, and soon thereafter, Dr Rodeck performed fetoscopy in cases of spina bifida diagnosed in the second trimester. King’s College in London quickly became a referral center for cases of suspected fetal anomalies. In 1978, he and Stuart published a paper in The Lancet on the use of fetoscopy for the early prenatal diagnosis of neural tube defects.¹⁶ A breakthrough occurred when Dr Rodeck obtained pure fetal blood from the cord insertion by ultrasound-guided fetoscopy.¹⁷ “I was his first assistant during the procedure,” Stuart said, “and I remember Charles’ excitement as he immediately recognized that direct access to the fetal circulation could begin a new era in prenatal diagnosis.”

Together, they realized the need to establish an institute devoted to fetal medicine based on ultrasound and this new fetoscopic technique. With the help of Dr Michael Brudenell, a supportive National Health Service Consultant at King’s, they invited Sir Philip Harris, a renowned English businessman, and his team to visit King’s College in 1982. They showed a video of a live fetoscopy, during which one of the observers fainted, hitting his head hard on the way down to the floor. Stuart recalled his whispered comment to Dr Rodeck: “I think that’s our grant, gone.” A few days later, however, they heard from Sir Philip Harris, who was excited about the project and wanted to invest. The Harris Birthright Research Centre for Fetal Medicine was thus established and continues to operate today. At King’s, the academic Department of Obstetrics and Gynecology was located on the ninth floor of the Ruskin Wing in two parallel corridors, and the Harris Birthright Centre was assigned to one of the corridors, with Dr Rodeck taking a lead role.

Of historical interest, the Princess of Wales, Diana Spencer, who was an expectant mother at that time, was present to open the Harris Birthright Centre (Figure 10). Stuart served as the sonographer to the British royal family for several years, scanning both Princess Anne and Princess Diana during their pregnancies. He often visited Buckingham Palace with his mobile ultrasound machine.

Figure 10.

Dr Campbell with the Princess of Wales, Diana Spencer, at the opening of the Harris Birthright Research Centre for Fetal Medicine at King’s College Hospital, 1982

Photo courtesy of Dr. Campbell.

In 1980, the Centre welcomed Dr Kypros Nicolaides to the department, and after initial training, he became an assistant to Dr Rodeck. The Prenatal Diagnosis Unit made many important fetoscopic “firsts,”¹⁸ but Dr Nicolaides was eager to go beyond fetoscopic blood sampling and pursue “cordocentesis”; although it was Dr Nicolaides who coined this term, this technique had already been described.¹⁹

When Dr Rodeck left King’s to assume the role as Chair of Obstetrics and Gynaecology at the Royal Postgraduate Medical School based in Queen Charlotte’s Maternity Hospital, Dr Nicolaides assumed leadership of the Harris Birthright Centre. “Kypros continued growing from strength to strength, and we worked together on umbilical cord sampling²⁰ and correlating fetal blood gases with Doppler studies of fetal well-being,” Stuart said.²¹ Just when it appeared that cordocentesis had replaced fetoscopy for all invasive procedures, fetoscopic laser surgery emerged as a particularly useful technique in treating twin-to-twin transfusion syndrome by sealing off the communicating vessels.²²

Fetal echocardiography

In tandem with these developments, Stuart continued to explore early diagnosis of fetal malformations, and he trained a team of young physicians to handle the increasing number of referrals to King’s Prenatal Diagnosis Unit. In 1978, Stuart was approached by a gifted pediatric cardiologist, Dr Lindsey Allan from Guy’s Hospital in London, to collaborate in the prenatal diagnosis of congenital heart disease. Stuart and Dr Allan produced a landmark study: the first detailed anatomic study of the fetus published in 1980.²³ Along with the team at Guy’s, they examined fetal cardiac anatomy using real-time two-dimensional ultrasound in 200 pregnancies from 14 weeks of gestation until term, identifying eight diagnostic scanning planes. In a subset of patients within this study, they demonstrated echographic and anatomic correlates. “One longitudinal and one transverse plane could be seen in nearly all patients,” Stuart said. “The team made considerable improvements in the recognition of the other planes with the second hundred group of patients, as our experience and anatomical understanding increased.”

A second paper in 1981 detailed real-time examinations of the fetal heart made in 21 women before midtrimester termination, mainly for chromosomal abnormalities.²⁴ Eighteen hearts were correctly identified as normal; two with atrial septal defects and one with a coarctation of the aorta were also correctly diagnosed; and there was one false-positive diagnosis of a ventricular septal defect. Thus began fetal echocardiography, as Dr Allan’s systematic scanning planes went into use worldwide to diagnose fetal cardiac defects and fetal arrhythmias. Dr Allan continued to work with the King’s team^25,26 and increased her activities with the fetal cardiology unit at Guy’s as the influence of her work grew.

Concurrently, Stuart pursued studies in fetal well-being, fetal behavioral and Doppler studies in particular. In 1982, Doppler ultrasound was first applied to study the fetal aorta by Dr Sturla Eik-Nes of Norway and Dr Karel Marsal of Sweden.²⁷ As a frequent visitor to Lund and Trontheim, Stuart became enthused by these early developments in Doppler and teamed up with London engineer Mike Teague, who Stuart described as “absolutely brilliant.” They built equipment that not only enabled the visualization of fetal vessels but also had duplex imaging and a Doppler probe capable of measuring velocities and the pulsatility index of the fetal aorta, carotid arteries, and smaller vessels such as the renal arteries. Stuart considered himself fortunate to have a dedicated team of research fellows, especially Dr David Griffin, a “devoted and wonderful research fellow,” who initiated many of the team’s fetal Doppler studies.²⁸ The fetal Doppler group examined fetuses in normal pregnancies at 17–42 weeks of gestation and demonstrated the redistribution of flow that occurs after 32 weeks.²⁹ Other leading members of the team were Drs Titia Cohen, Katia Bilardo, Sanjay Vyas, Susan Bewley, Gerald Hackett, David Little, and Sarah Bower. Furthermore, with the team led by Dr Nicolaides just across the corridor, collaborative studies were conducted to correlate fetal Doppler parameters with fetal blood gases.^30,31

Doppler studies of the uterine artery

Up to this time, the focus of Doppler to assess fetal wellbeing concentrated on the umbilical artery and fetal vessels, yet Stuart was very keen to discover whether flow in the uterine arteries could be determined. Another revelatory moment in Stuart’s career came about when he and Dr Griffin first identified the uterine artery waveform: soon they became adept at identifying the waveform with their duplex equipment, which was altered by the development of a “notch” and a high pulsatility index in association with preeclampsia/fetal growth restriction.³² “Two-dimensional images of the uterine artery lateral to the lower segment could be difficult to obtain,” he said, “but two years later, color Doppler became available and made screening for the prediction of preeclampsia much more reliable and quicker to accomplish.”

Using pulsed Doppler ultrasound to examine blood-flow velocity profiles in the uterine vessels during the second and third trimesters, the team created profiles of normal pregnancies and those with complications such as hypertension, proteinuria, and fetal growth restriction. The study supported the conclusion that the technique may provide an early warning for the development of preeclampsia or fetal growth restriction.³³ Eight years later, Stuart published a paper that introduced the concept of screening for preeclampsia and fetal growth restriction based on early uteroplacental waveforms.³⁴ In subsequent years, Stuart and his team studied uteroplacental blood flow in pathologic conditions and published on the use of Doppler ultrasound imaging to investigate uteroplacental circulation,³⁵ the assessment of both fetal and uteroplacental circulation in severe second-trimester oligohydramnios,³⁶ and the examination of the uteroplacental vessels in anembryonic pregnancies, ectopic pregnancies, and spontaneous abortions to improve understanding of the pathophysiology of early placentation.³⁷

In the mid-1990s, Stuart recalled that “an outstanding researcher,” Dr Kurt Hecher from Austria, joined the department and carried out meticulous studies on the fetal venous system, including the ductus venosus, finding a-wave reversal to be indicative of development of fetal acidemia and severe fetal compromise.³⁸ Dr Hecher is now Professor and Chair of the Department of Obstetrics and Prenatal Medicine at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany.

Early human development unit

In parallel with these advanced studies on late fetal compromise, Stuart established studies on first-trimester fetal development with the help of Drs Eric Jauniaux of Belgium and Davor Jurkovic of Croatia. They were supported by Dr Gonzalo Moscoso of Peru, who was employed by the King’s College Anatomy Department and who produced some of the finest anatomic and electromicroscopic studies of early pregnancy. Much of their research was original, and the team published papers on early placental morphology and the biochemistry of coelomic fluid and the yolk sac.³⁹ The coelomic space is present between 6 and 10 weeks of gestation, and it was questioned whether a culture of the coelomic cells would allow accurate prenatal diagnosis at an earlier stage than chorionic villous sampling. After initial hope that this approach would be successful,⁴⁰ it turned out that the miscarriage rate for the new technique was unacceptably high. Stuart lamented that, sadly, not all the innovations at King’s would turn out to be successful.

Dr Moscoso was later extremely helpful in obtaining support from the University of Lima for comparative studies on fetal growth and circulation at the altitude of 4300 m in Cerro de Pasco in the Andes and at sea level in Lima. An Austrian fellow, Dr Elizabeth Krampl, spent six months in Peru on growth and Doppler studies.^41,42 No previous research had involved maternal-fetal studies at such high elevation, and as expected, low maternal O₂ content, low pO₂, and high hematocrit were found in the Cerro de Pasco group. The team documented significantly slower fetal growth rates at altitude from 26 weeks of gestation onward, but Doppler studies showed no evidence of centralization of flow in these fetuses, suggesting that slower growth rates were unrelated to fetal hypoxia. Indeed, uteroplacental blood flow was significantly greater in women who lived at high altitude, which left the higher incidence of preeclampsia unexplained.

The story of nitric oxide in premature labor and preeclampsia

Inspired by seminal work on the biology of prostaglandins and nitric oxide, which led to two Nobel Prizes in Physiology and Medicine in 1982 and 1998, Dr Christoph Lees, Dr Salvador Moncada, and Stuart worked to explore whether a nitric oxide donor (nitroglycerin) could be used as a tocolytic agent, given that it relaxes vascular smooth muscle and the myometrium. A randomized clinical trial showed that nitroglycerin decreased the frequency of contractions and prolonged pregnancy for a short time but did not significantly reduce the rate of preterm delivery.⁴³ In this way, nitroglycerin was added to the list of potential tocolytic agents.

Realizing the importance of nitric oxide in vascular biology, Dr Lees and Stuart also used s-nitrosoglutathione (GSNO) for the treatment of early preeclampsia and HELLP syndrome. This particular nitric oxide donor inhibits platelet aggregation, induces vascular relaxation (improving hypertension), and improves renal function and uterine blood flow.⁴⁴ This promising approach, which targets the vessel wall and platelets, remains an interesting area for further investigation.

Ultrasound for in vitro fertilization and screening for ovarian cancer

An avid reader of the literature, Stuart became interested in a paper from Denmark about transabdominal ultrasound-guided egg retrieval: “This must be a way to make egg collection easier and less invasive than the then-practiced laparoscopic egg retrieval.” This observation led him to invite Dr John Parsons, who had experience with IVF, to join his department.

“We had no IVF service at this time, only two clean rooms and an ultrasound machine available, but John did an amazing job. Within a few weeks, he’d built a laboratory and developed the first ambulatory program,” Stuart recalled.⁴⁵ “In those days, the cast-off ultrasound machine was usually assigned to the IVF Unit, but I was eager to use advanced equipment, including 3D and Doppler, to determine if parameters such as endometrial vascular grading and perifollicular blood flow would add to our understanding of endometrial and follicular physiology and improve success.” This innovation led to two original papers that influence IVF protocols today.^46,47

It was a natural extension of his work at the IVF unit for Stuart to gravitate into the field of gynecology. Stuart attended a meeting in which there was discussion about ovarian cancer being largely asymptomatic, leading to a late diagnosis. Thinking about the unit’s steady influx of patients regularly monitored for follicle growth, Stuart proposed this query: “Why not go further and look at the ovary in older women to try to predict ovarian cancer earlier? Why can’t we screen women every year to identify morphological and volumetric changes associated with early ovarian carcinoma?”

To investigate this question, Stuart set up a study in 1985 and began annual transabdominal screening of women older than 45 years. Of 3000 women scanned, stage I ovarian cancer was detected in five patients. The results were published in the British Medical Journal in 1989,⁴⁸ and Stuart promptly wrote to the UK Medical Research Council applying for a grant to continue ovarian cancer screening—this time, based on an annual transvaginal scan.⁴⁹ However, his application was declined. Shortly thereafter, Dr Ian Jacobs, Chair of the Department of Obstetrics and Gynecology at St. Bartholomew’s Hospital in London, applied for a grant to use serum cancer antigen 125 (CA125) for the detection of ovarian cancer. His proposal was accepted, but on one condition—he must include Stuart and ultrasound in the screening program. “The Medical Research Council got the best of both of us,” Stuart said.

The project, a huge undertaking, aimed to determine whether screening could significantly reduce the mortality rate from ovarian cancer; the study group consisted of more than 200,000 asymptomatic women who were older than 50 years. Women were randomized to a control group of 101,359, an ultrasound arm of 50,539 screened with transvaginal ultrasound alone, and a multimodal arm of 50,640 screened with serial CA125, supplemented with ultrasound to reduce the false-positive rate. The trial involved annual screening for 10 years and a follow-up screening a few years later.

The results, published in 2016, showed a reduction in mortality compared to the control group, but the results were not as exciting as Stuart had hoped. The primary analysis, using a Cox proportional hazards model, gave a nonsignificant reduction over years 0–14 of 15% in the multimodal screening arm and 11% in the ultrasound arm when compared to the control arm. However, there was a late effect in mortality with a mean reduction of 23% for years 7–14 in the multimodal group and 21% in the ultrasound group.⁵⁰ Stuart suggested that a different statistical model to demonstrate the late effect might have shown an overall significant decrease in mortality. Interestingly, ultrasound imaging detected 95% of the cases with borderline ovarian cancer, making this technique valuable in the identification of slow-growing tumors. “One problem with using ultrasound is that aggressive cancers go undetected between the one-year screening intervals,” he said, “whereas serum CA125 testing can be done more often.”

The research team plans to continue analysis of the data and conduct another follow-up this year, and Stuart is optimistic that they will show a significant drop in mortality enough to persuade healthcare providers to recommend routine screening for ovarian cancer. Stuart noted how well the trial was run and credited collaborators Dr Jacobs and Dr Usha Menon for “being wonderful organizers and closely surveilling their team of gynecologists and sonographers in the study.” Dr Jacobs now serves as President and Vice-Chancellor of the University of New South Wales in Sydney, Australia, and Dr Menon, who is now Professor of Gynecological Cancer and Head of the Gynecological Cancer Research Centre at University College London, was Dr Jacob’s right-hand person at the beginning of the study and now runs the project on-site.

During that time, Stuart was also involved in studies investigating the use of ultrasound in combination with color flow imaging as a means to detect endometrial cancer^51–53 and ectopic pregnancies,^54,55 further underscoring the importance of ultrasound imaging as an effective tool in the diagnosis and management of pregnant and nonpregnant women alike.

Founding the International Society of Ultrasound in Obstetrics and Gynecology

In 1988, Stuart and a group of his colleagues established a scientific society with a focus on imaging—ultrasound in particular. His vision was to bring together the medical and scientific communities to “(1) act as a forum for in-depth analysis and presentation of advances in ultrasound diagnosis in all aspects of the specialty; (2) be an influential body, setting standards for medical training, and monitoring the safety of ultrasound in obstetric and gynecological diagnosis; and (3) hold a major conference every year to explore the most recent developments of ultrasound in obstetrics and gynecology, and to bring together doctors who are using ultrasound to improve clinical care.”⁵⁶ They accomplished this enormous task in less than three years.

Once Stuart announced the first World Congress would be held in London in January 1991 (Figure 11), attendance swelled to more than 1000 delegates: the event was a testimony to Stuart’s leadership. The whole Congress was organized by a small team and led by Stuart, his executive assistant Ms Bobbie Andress, and a start-up company, Meeting Point, that specialized in conference planning. With bravado and without fear, Stuart selected the most prestigious, expensive conference center in London, the Queen Elizabeth II, to house the Congress. The banquet, held at the Dinosaur Hall in the Natural History Museum, remains a memorable event for those who attended. To highlight the opening ceremony, Stuart asked for volunteers among the luminaries of ultrasound to entertain the delegates. Dr Hobbins played the piano; Stuart sang a duet with a young physician from the Philippines.

Figure 11.

The inaugural issue of Ultrasound in Obstetrics and Gynecology and the program for the first ISUOG meeting, 1991

ISUOG, International Society of Ultrasound in Obstetrics and Gynecology.

Photo courtesy of Dr. Campbell.

Since that time, ISUOG has become the premier forum for scientific advances in imaging for our discipline. Serving as President from 1991 to 1998, he oversaw the scientific programs in Bonn, Germany; Las Vegas, Nevada; Budapest, Hungary; Kyoto, Japan; Rotterdam, Netherlands; Washington, DC; and Edinburgh, Scotland. ISUOG’s membership has now grown to include more than 15,000 members from more than 140 countries. Under the leadership of the current president, Prof. dr C.M. (Katia) Bilardo of Italy and Netherlands, the Society continues to provide strong educational and outreach programs globally. ISUOG’s long-term vision is access to ultrasound for every woman and competency of every scan to improve women’s healthcare.

ISUOG recognized Stuart’s contributions to the field with its Ian Donald Gold Medal in 1992 and the ISUOG Honorary Fellowship Award in 2002. The ISUOG Board of Directors also honored Stuart’s legacy to obstetrics and gynecology with the creation of the “Stuart Campbell Award for Education,” bestowed upon a recipient whose exceptional dedication to the advancement of ultrasound through education has been constant throughout one’s career. Stuart continues to be recognized at each ISUOG Congress: the Stuart Campbell Lecture is delivered by esteemed figures in our discipline.

Editor in Chief of Ultrasound in Obstetrics and Gynecology

While organizing the first ISUOG Congress, Stuart decided that the Society needed its own scientific journal. He approached Mr David Bloomer of Parthenon Publishing to launch this new initiative. The first issue of Ultrasound in Obstetrics and Gynecology (UOG) coincided with the ISUOG Congress in London in 1991 (Figure 11). UOG’s incubation period lasted one year, and Stuart supported its development as an international journal. He encouraged submissions from non-English-speaking countries, thus welcoming good scientific work without requiring correct English syntax and grammar. Stuart, as Editor in Chief, penned the first editorial, “Ian Donald’s child comes of age.”⁵⁶ Acknowledging the revolutionary origin of this specialty, he praised Dr Donald’s invaluable contribution and unshakable honesty portrayed in the 1958 “magnum opus,” a report of the first ultrasound images of obstetrical and gynecologic anatomy and pathology.⁵⁷ Further, Stuart wrote to the first readers and potential contributors to UOG:

“Above all, we would like your letters, be they observations on aspects of clinical practice, or criticism of papers contained in previous issues. We want the journal to be both informative and entertaining and to reflect the concerns and interests of all doctors who use ultrasound in obstetrical and gynecological diagnosis...there will be a section for short communications, for we believe a series of illustrative case reports can be as influential on good clinical practice as the best-designed prospective trial. We aim also to provide historical items and information about national societies.”⁵⁶

To strengthen the international appeal of UOG, Stuart recruited physicians worldwide to serve as Editors and members of the Editorial Board. Further underscoring UOG’s inclusive commitment to publish good science and medicine, he appointed a talented, savvy, dedicated, and thorough Editorial Manager, Ms Sarah Hatcher. In 1998, Stuart said of Ms Hatcher, “She is polite, friendly, and quietly efficient. To those of you whose first language is not English, it is Sarah who will convert your inelegant prose to the masterpiece of impeccable syntax which you so proudly show to your colleagues.”

Instrumental in the success of the establishment of UOG was Dr Lawrence Platt: “Larry was the greatest supporter of the Society in the United States,” Stuart said. “He was always an enthusiastic member of the Society right from the start, and he served on our first Executive Committee and Editorial Board. He was hugely influential in popularizing the ‘White Journal’ in the States and of course became our President in 2004.”

Five years after the first issue, Stuart remarked that UOG had moved from infancy through childhood to enter adulthood. He announced that UOG was indexed by all extraction systems, and that its 1994 impact factor placed the Journal among the top 10 in obstetrics and gynecology, an exceptional feat that testifies to Stuart’s vision and editorial wisdom.

The “White Journal,” as it is affectionately now known, currently ranks number three in impact factor among all journals in obstetrics and gynecology and provides its content free of charge after one year of publication.

From King’s College Hospital to St. George’s Hospital

In 1996, Stuart left King’s College to become Chair and Professor of the Department of Obstetrics and Gynecology at St. George’s Hospital in London, where he was an early advocate for the three-dimensional (3D) ultrasound scan as an important catalyst for maternal-fetal bonding. Stuart focused his time at St. George’s on recruiting new talent and increasing the department’s research profile. There, he established the first Fetal Medicine Unit, led by Dr Yves Ville, set up a gynecologic ultrasound unit led by Dr Tom Bourne, and instituted an IVF unit led by Dr Geeta Nargund, Medical Director of the Diana, Princess of Wales Centre for Reproductive Medicine at St. George’s Hospital.

Now 65 years young, Stuart was still heavily involved in research and focused on 3D ultrasound. However, the United Kingdom has a strict retirement policy for professors who reach 65 years of age. Unlike their counterparts in the United States, who are able to continue teaching and research activities within their departments, academicians in the United Kingdom are fully retired from university life. Not ready to give it up, he continued his practice in the private sector.

At first, the “retiree” concentrated on the use of 3D ultrasound and imaged developing fetuses throughout gestation. Applying his command of science to the arts, he also wrote “a few books” and played an important role in producing the acclaimed documentary In The Womb for National Geographic, which aired in 2005. Around the same time, Stuart described a novel method for diagnosing cleft palate with a reverse-face view, collaborating with Dr Christoph Lees, Director of Fetal Medicine, and Dr Per Hall, an orofacial surgeon at Addenbrooke’s Hospital, based in the Cambridge Biomedical Campus.^58,59 This advance gave detailed, reliable information on congenital defects of the fetal palate, whereas previous methods revealed only defects of the lips and alveolar ridge.

Continuing his collaboration with Dr Nargund, Stuart became more interested in the mild and natural cycle of IVF that she pioneered in the United Kingdom.⁶⁰ They eventually set up a full clinic in reproductive endocrinology and infertility, establishing the CREATE Health Centre for Reproduction and Advanced Technology (CREATE Fertility) in Wimbledon.

Informed and inspired by their patients, they found themselves quite busy, as women learned they could go through IVF without feeling menopausal or bloated, as often happens after the high stimulation of the ovaries through traditional IVF. Stuart and Dr Nargund concentrated on reducing the number of eggs collected, even though the standard in the United Kingdom at that time was to maximize egg collection. However, with mild IVF, the idea was to collect an adequate number of eggs of good quality, but not the maximum possible, to avoid ovarian hyperstimulation.

The clinic became popular and expanded into other cities, with additional centers now in St. Paul’s London, Birmingham, Manchester, Bristol, and Copenhagen. Stuart continues to teach sonography at these centers and has recently published a two-part review on predicting the quality of the oocyte and receptivity of the endometrium with color Doppler and 3D ultrasound.^61,62

Professional activities and awards

Stuart is a Fellow of the Royal College of Obstetricians and Gynaecologists, the Royal College of Physicians of Edinburgh, and the American College of Obstetricians and Gynecologists. He has been recognized as an Honorary Fellow by several scientific societies, including the American Institute of Ultrasound in Medicine, the British Medical Ultrasound Society, and the Italian Society of Echography in Obstetrics and Gynecology. Stuart served as President of the Royal Society of Medicine’s Section of Obstetrics and Gynaecology in 1995. Stuart and his wife, Jane, were also honored to meet Pope John Paul II in 1998 (Figure 12).

Figure 12.

Meeting Pope John Paul II in the United Kingdom with Jane, 1998

Photo courtesy of Dr. Campbell.

Family life

Stuart and Jane met when he first moved to London in 1968 and rented a flat in a building where she also lived. Jane, then a surgical nurse, had decided to complete her training in midwifery and joined the nursing team at Queen Charlotte’s Maternity Hospital around the same time that Stuart began his work there. Their common interest in medicine brought them together, and two years later, Stuart and Jane were married. Their four children, Bruce, Tiffany, Oliver, and Charlie, and their grandchildren still gather often in the family home (Figure 13).

Figure 13.

The Campbell Family Christmas, 2019

Back row: Bruce and Alison (eldest son and his wife), Tiffany (daughter), Archie (grandson), Jeffrey (Tiffany’s friend), Charlie (youngest son). Front row: Stuart, Jane, Beatrix (granddaughter), Laura (mother of daughter-in-law Crystal), Deirdre (her wife). Not pictured: Crystal (Charlie’s wife) and Oliver (son).

Photo courtesy of Dr. Campbell.

Life outside of medicine

Still working six days a week, Stuart finds reading time hard to come by. Sharing that he was an avid reader growing up, he developed a great love of poetry, enjoying the classics, including John Keats, and metaphysicial poets such as John Donne, but the works of Shakespeare are his greatest love. A well-accomplished scientific writer, he often thinks about writing a book one day—a novel or a bit of history. He appreciates writers whose works are simple, clear, and entertaining, and he credits the style of George Orwell as an influence on his own writing.

Stuart also plays golf every Sunday morning, occasionally on Fridays, and enjoys watching televised golf games—not necessarily to see who wins but to understand the techniques and to learn from professionals. He is drawn to the precision of the game and is always adjusting his swing to improve (Figure 14).

Figure 14.

Posing with a golf trophy.

Photo courtesy of Dr. Campbell.

Reflections

Looking back on his career, Stuart said he is most proud of his mentorship and encouragement of young physicians: “I gave them ideas and let them run with it.” Stuart mentioned that to build a successful department, it was important to be involved with team members individually, understand what they are thinking, and evaluate them. “I like to see obsessional people. I like to see people who, once they get the idea, focus on it and develop it. I believe that optimism and enthusiasm are essential for leadership.” He also noted it is a two-way street with trainees: “You inspire them with ideas, and then they will inspire you back.”

Stuart told me that he is proud of the department he created at King’s and regards his obsession with accuracy as his greatest contribution to the field of obstetrics and gynecology. When asked what made King’s such a fertile environment for new ideas, Stuart told me: “I didn’t want to control everything. Many of the fantastic innovations were not mine; it’s because I was open to new ideas and encouraged them to develop. And I had a liking for appointing people who were maybe a little bit challenging and idiosyncratic. I think you must do that as head of a department; you don’t necessarily appoint people who have been up the traditional path. If you interview somebody, and they show a bit of flair and imagination, go for it.”

Stuart has dedicated more than 50 years to the study of fetal biometry, and he pioneered ultrasonic methods for diagnosing fetal abnormalities, assessing fetal growth, and improving egg collection procedure for IVF patients. Stuart’s influence in the field of obstetrics and gynecology can be summarized by his own self-description: “an innovator and a good teacher, and, really, not a bad person at the end of the day.”

On the occasion of his 80th birthday, there was a special reception in Stuart’s honor at the House of Commons of the United Kingdom where he was surrounded by friends and family (Figures 15 and 16).

Figure 15.

Reception at the House of Commons in London, United Kingdom, honoring Stuart’s 80th birthday.

Left to right: Dr Stuart Campbell, Dr Geeta Nargund, Dr Willem Ombelet and Mrs Hilde Ombelet, Dr René Frydman and Mrs Monique Frydman.

Photo courtesy of Dr Campbell.

Figure 16.

Members of the Create Fertility team celebrate with Stuart at the House of Commons, London, United Kingdom.

Left to right: Dr Spiros Liatsicos, Dr Anastasis Anastasiadis, Dr Ippokratis Sarris, Dr Melina Stasinou, Dr Stuart Campbell, Dr Spiros Chouliaras, Dr Vasileios Sarafis.

Photo courtesy of Dr Campbell.

For his transformative and substantial contributions to obstetrics and gynecology and for improving the care of women, the American Journal of Obstetrics & Gynecology recognizes Dr Stuart Campbell as a “Giant in Obstetrics and Gynecology.”

Biography