Maternal-fetal medicine (MFM) as a subspecialty was introduced in the Netherlands in 2006, together with three other subspecialties, fertility, oncology, and pelvic floor. General obstetric training is a highly qualified and organized 6 year program, with the majority of Obstetrician-Gynecologists going into practice in one of the 70 hospital without a fellowship training. MFM specialists work in one of the nine centers with a neonatal intensive care unit, seven of which are University Medical Centers. In this review, the role of these MFM centers in the obstetric care in the Netherlands is described, with some features unique compared to other European countries, such as the 13% home delivery rate. A more detailed description is given of the history and organization of fetal therapy, centralized already for more than 55 years in a single national referral unit, the Leiden University Medical Center.
The Netherlands: demographics
The Netherlands, sometimes called “Holland”, is the country of the Dutch people. It is positioned in the North-West of Europe, bordered in the East by Germany and in the South by Belgium. The West coast is a more than 400 km long beach at the North Sea, across this sea lies the United Kingdom (Fig. 1). From North to South is only about 300 km, and with 150 km from the coast to Germany the area is only 41 543 km2, similar to Denmark and Switzerland, and about 0.4% of the area of China. With a relatively dense population of 17.5 million people (12% of China) this means 411 persons per km2 (in China 15 per km2). However, distribution is quite unequal, with the majority living in the West, with more than 1 000 persons per km2 (Fig. 2). There are no mountains, even hardly any hills, the country is completely flat except for a small part in the South-East corner. These characteristics, a small, flat, densely populated country, with a good infrastructure of roads and railways, have important implications for the organization of health care. Life expectancy is 82 years, and currently over 3.3 million or almost 20% of the population is over 65 years of age, and this percentage is increasing. The Netherlands ranks No. 14 in the list of richest countries in the world (www.imf.org). Unemployment rate is low, with 3.5% the No. 3 lowest in Europe.
Medical education and residency in obstetrics and gynecology
Students entering Medical school at one of the seven Dutch universities have typically followed 6 years of secondary school, from the age of 12 to 18 years. The study is currently structured as a Bachelor (3 years), Master (3 years) with the last 1.5 years being internships in several hospitals. Those interested to become specialists in Obstetrics and Gynecology usually first need to work as a house officer not-in-training, or do research, or both, to be able to compete for the limited number of training positions. Once in training, the program takes another 6 years of which the last two can be done in a specific area of interest (obstetrics, general gynecology, fertility, oncology, etc). About 25% of residents completes a PhD program (3–4 years), before, during or after their general specialty training. European regulations now strictly limit the working hours for residents, to an average of 48 hours per week including nights on call. There are currently around 900 specialists in obstetrics and gynecology in the Netherlands, of which 50% are women. Among the 400 residents; however, 83% are women.
Following residency, only a minority of Obstetrician-Gynecologists specialists continue to a subspecialty fellowship. Most of the non-university hospitals do not require their obstetric staff to have completed an MFM fellowship. Also in the seven university hospitals, an MFM fellowship is not compulsory. Each university hospital has one or two MFM fellowship positions, and due to language restrictions, very few come from abroad. The 2-year MFM fellowship is a fully paid clinical position, with modules including neonatology, genetics, intensive care, prenatal diagnosis and ultrasound, maternal medicine and obviously high-risk obstetrics. In the past, all fellows learned to do invasive diagnostic procedures (chorionic villus biopsy and amniocentesis), but since the rapid decline in numbers due to cell-free DNA screening, only a selected group is now offered this training. All fellows have a PhD. Only a few MFM specialists have done their fellowships, full or in part, abroad, with Canada (Toronto), United Kingdom (London), or Australia (Brisbane, Melbourne) as most popular destinations.
Obstetric care in the Netherlands
Birth rate is slowly declining, with, in 2018, 162 464 children born. More than 80% of women, when they know they are pregnant, first visit a midwife. These well-trained (4 years education), often independently working midwives do a first triage, with history, physical examination and a dating ultrasound, and then decide whether the woman is considered high risk (with referral to an obstetrician) or low risk, in which case the midwife does all the prenatal care. During the course of the pregnancy, and during delivery, many women at first considered low risk develop a problem for which they are referred to an obstetrician. Ultimately, 28% of women deliver under the care of a midwife only, half of this group in a hospital (with the obstetrician, operating theatre, and pediatrician stand-by in case of problems). In 2018, 13% of births took place at home.1 This relatively high percentage, for European countries, a unique feature of Dutch obstetric care, is considered quite safe because of two reasons. The first is that these women are very carefully triaged to be at really low risk by the well-trained midwives. The second reason is that from any home in the country, an ambulance can take a patient to a hospital within 45 minutes, and in the majority of cases within 30 minutes from making the emergency phone call. Although the percentage drops annually, this culture of home birth and midwife-led care is part of the general view by the public that pregnancy is not a disease, but a natural event that generally goes well without the need for doctors. This view is also reflected in the low rates of epidural analgesia (22%) and cesarean sections (15%). Elective cesarean section is done in only 7.6%. Induction of labor is done in 22% of pregnancies.1
Maternal mortality is a very rare event, with less than 10 cases per year. A decrease was seen in the last decade, with more aggressive management of preeclampsia. About two-third of women that died directly or indirectly caused by pregnancy or childbirth were immigrants, often with low socio-economic status.
Perinatal mortality in the Netherlands is with 4.8 per 1 000 live births the exact average for Europe. When calculated from 22 weeks onwards, perinatal mortality is 7.9 per 1 000. Fetal death (28 weeks or more) occurred in 2.8 per 1 000, neonatal death up to 28 days in 2.0 per 1 000. In ten European countries, the outcome data are better (www.europeristat.com). A government-installed task-force is working analyzing causes and finding ways to improve our outcomes, in part by improving collaboration between the independent midwives and the obstetricians. Another focus is on the disproportionate contribution of women with low socio-economic status to the poor outcomes, with programs for better pre-pregnancy counseling and interventions, such as stop smoking help.2
Like in many countries, there is a routine screening program which includes first trimester blood testing for infections, blood group, Rh factor, and red cell alloantibodies for all women. Testing for hemoglobinopathies and sickle cell disease is only done in specific risk groups. All women receive an ultrasound between 8 and 12 weeks for dating, exclusion of ectopic and multiple pregnancy. All women are asked whether they are interested in screening for fetal trisomy. If so, they have a 20-minute counseling session with a certified counselor. Until 2017, the screening test for fetal trisomy risk available was the first trimester combined test (FCT). In the past 3 years a nationwide prospective study is performed in which non-invasive prenatal testing (NIPT) is offered as first-line test, with a choice for screening for trisomy 21, 18, and 13 only, or with addition of low resolution whole genome testing, looking at all chromosomes except X and Y. In this TRIDENT 2 study, around 40% of women choose NIPT, 3% request the FCT, and more than half of the women decline any screening for chromosomal anomalies.3 Of those choosing NIPT, 75% are interested in the additional findings. Of importance, women have to pay a part of the costs of the trisomy screening (FCT or NIPT) out of their own pocket (175 euro). More than 95% choose to have a 20-week anomaly scan, which is completely covered by basic health insurance. In 2021, a large nation-wide study evaluating the use of a routine first trimester anomaly scan will be started. If at routine screening, an anomaly is found or suspected, the pregnant woman is referred to the regional MFM center, where a full diagnostic work-up is done including detailed genetic analysis using microarray and increasingly whole exome sequencing, detailed ultrasound examination occasionally supplemented by magnetic resonance imaging, followed by multidisciplinary counseling.
The Netherlands is divided in seven regions with each their own tertiary care or university hospital center, to which hospitals in the region refer pregnancies with fetal anomalies or high-risk obstetric or maternal conditions. Apart from these seven university hospitals, two large teaching hospitals also have a neonatal intensive care unit.
The annual number of births in the MFM centers is only around 3 500, most of which are considered “high-risk”: preterm births, fetal anomalies, multiples maternal complications, and so on. Even in these centers, cesarean section rates are relatively low, between 20% and 30%. A few years ago, these MFM centers all had one or more satellite centers where invasive prenatal diagnosis was also done, but since the introduction of NIPT this is now centralized in the MFM centers in university hospitals. Patients with threatened preterm birth or early preeclampsia before 32 weeks are referred to the regional MFM center. Very preterm born neonates can be actively resuscitated from 24+0 weeks’ gestation onwards, although parents can also elect comfort care without resuscitation between 24 and 26 weeks.
An important factor, which may be quite different between countries, is the financial and insurance structure in the Netherlands. Most medical specialists, and all of the University-based MFMs, have a fixed monthly salary, and no private practice. Referrals, or number of procedures performed, are therefore not influenced by financial aspects. Also for patients, pregnancy care including fetal procedures is fully reimbursed by their health insurance. Everyone in our country is required to have a basic health insurance, which covers all regular health care. There is an own risk of 385 euro per person per year, but for pregnancy care this own risk is not used. People with low income receive governmental support for their health insurance premium. For rare procedures such as intrauterine transfusion or laser for twin-twin transfusion syndrome, a reimbursement code was never negotiated and is therefore done on the hospitals budget. This may have contributed to the fact that in the Netherlands, other centers were not that interested in performing those procedures. Most MFM centers have 8–10 MFM specialists, one or two fellows, and around ten residents. In our Leiden center, we have two dedicated, experienced nurses to support our prenatal diagnosis and fetal therapy procedures.
National fetal therapy center
In 1964, a young fellow from the Leiden university hospital, Jack Bennebroek Gravenhorst, traveled to New Zealand, to learn the new technique of intrauterine blood transfusion from its inventor, Dr. William Liley.4 At that time, Rhesus hemolytic disease was one of the major causes of perinatal mortality and morbidity. When Jack returned, he convinced his boss and colleagues to allow him to start the first Dutch fetal therapy program. For 35 years, fetal blood transfusions and occasionally platelet transfusions were the only treatments offered, up to 100 procedures in around 35 pregnancies per year. Referrals came from the entire country, no other center was interested to put time and effort into this rare, complex and not reimbursed procedure and the time-consuming care for these patients. In 1986, after a study trip to Paris, the team switched from intraperitoneal to direct intravascular transfusion, enabled by the increasing quality of ultrasound machines. With experience and improved technique, fetal survival rates gradually increased, from 25% in the 1960 to 95% in the past two decades.5
From the year 2000 onwards, an increasing number of fetal interventions were offered by the Leiden team. Laser surgery for twin-twin transfusion syndrome, bipolar cord coagulation or radiofrequency ablation in discordant monochorionic twins, thoraco-amniotic and vesico-amniotic shunting, and laser coagulation of pulmonary sequestration (pioneered by the Leiden group) became routine procedures for internationally accepted indications.6 Mentors during the early stages were Professor Jan Deprest from Leuven, Belgium and Professor Greg Ryan from Toronto, Canada. The centralized fetal therapy service meant that the team could gain a lot of experience in a relatively short time. In 2010, fetal balloon valvuloplasty was first performed in Leiden for severe aortic stenosis, to prevent hypoplastic left heart syndrome.
The Leiden Fetal Therapy center is, like most such centers in Europe and Canada, led by MFM specialists, closely collaborating with neonatologists, geneticists, pediatric subspecialists, and for magnetic resonance imaging diagnosis, radiologists. This is in contrast to many centers in the United States of America, where pediatric surgeons are in charge, assisted by MFMs.7
The small size of the country, and ease for patients to travel to Leiden if needed weekly or even more often, means that procedures can be carefully timed. The vast majority of women whose fetus is treated in utero delivers in the Leiden Center. Follow-up during pregnancy and even many years thereafter is relatively simple to organize, enabling the team together with neonatologist Professor Enrico Lopriore to perform short-term and long-term outcome studies with near 100% completeness.8–11
These studies provide excellent quality control and continuous learning for the operators. Formal quality control is done by regular audit and by Cumulative Sum analysis per operator.12,13 An annual report of all procedures and outcomes is published as part of the annual report on prenatal diagnosis and therapy of the Dutch Society for Obstetricians and Gynecologists.
In Table 1, the various procedures offered in Leiden are given, with average number per year and survival rates.
With less than 200 procedures in total per year, which are done by the Leiden team consisting of four operators, two specialized sonographers and two dedicated nurses, there was general consensus that one center in this small country was sufficient. Diluting the knowledge and experience by sharing these few patients with other centers was not considered to be in the interest of the patients. In addition, with a learning curve shown to require between 20 and 61 procedures to reach competence, it would take a new center many years to reach an acceptable level.13,14
However, around 2012, another university hospital considered starting a second fetal therapy center. The Dutch Society for Obstetricians and Gynecologists decided to install a committee, including representatives of Leiden and the center planning to start fetal therapy, that should write a consensus statement detailing the requirements and quality assurance to be fulfilled by any fetal therapy center. This report, available in English, was published in 2016.15 It contains criteria on the center, training and experience of operators, counseling, research, membership of international societies, follow-up, and quality control. The report acknowledged that to ensure high quality care in a fetal therapy center, more aspects than just operator skill and experience are important. The whole infrastructure, with expert knowledge and experience in diagnosing the various diseases for which fetal therapy might be indicated, determining the optimal time of interventions, 24/7 availability of an experienced team, a system for follow-up of treated patients, and full support of ethics committee and board of directors, is of vital importance. A complex issue to reach consensus on was the volume of patients or procedures needed to obtain and maintain adequate quality. For many rare, complex procedures in surgery, a minimum of 20 procedures per operator per year is often used, although the scientific evidence for this number is often lacking.16,17 Factors that play a role in the volume discussion are the fact that most procedures are done by a team, and experience of the sonographer and the assistant/nurse play a role as well. In many centers, rare procedures are often done with a second operator observing or stand-by. Some procedures are technically similar (ultrasound-guided needling procedures, or fetoscopic procedures) and could be combined to make up the annual volume per operator. New centers starting a fetal therapy service may at first not reach the required numbers, but may get more referrals after a few years, so criteria are not easily fulfilled right from the start.
Another complicating issue is that some fetal interventions, such as cardiac balloon dilatation, are so rare that even with one center per country, volume criteria may not be reached. This would be a reason to consider international centralization, with only a few centers in Europe offering certain very rare procedures. Although European travel is relatively easy, issues like insurance and language, and the fact that procedures may sometimes be needed urgently, hamper such a plan.
International collaboration and research
The Leiden Fetal Therapy center has a formal Alliance with the Swedish Karolinska Institute and the group of Jan Deprest in Leuven Belgium. In this Alliance, regular meetings with audit, discussion of rare complex cases, exchange of fellows and even assisting in difficult procedures is done. Outside of Europe, the Leiden team has close contacts with large fetal therapy centers including Mt. Sinai Hospital, Toronto, Canada; University College London, UK; First Maternity and Infant Hospital, Shanghai, China and the University of Texas Health Science Center in Houston, United States of America, for multicenter research projects and advice on complex cases.
Construction of MFM centers and in particular Fetal Therapy centers depends in part on geographic and logistic factors, health insurance structure, and of course numbers of complex patients in a region. A system of well-regulated referrals and collaboration, preferably without financial barriers for hospitals or patients, enhances quality of care. Rare diseases, maternal or fetal, requiring complex care and procedures by well-trained operators and their teams are best managed in specialized centers ensuring sufficient volume to maintain experience. In the Netherlands, a small and rich country with a well-organized infrastructure and an insurance system making all complex care independent of financial issues for both patients and doctors, a structure with one University-based MFM center per region, and a single national Fetal Therapy center works well. There is a lot of international collaboration, and active participation in multicenter research. Our system however is not easily transferable to other, much larger countries, or societies with a significant proportion of private health care. Still, some aspects of how the Dutch system is organized may of use for MFM colleagues around the world, just as the Dutch always enjoyed to learn from experiences of their international peers.
Conflicts of Interest
. Perined. Perinatale Zorg in Nederland Anno 2018: landelijke perinatale cijfers en duiding. Utrecht 2019. Available at: https://assets.perined.nl/docs/fc23b860-a5ff-4ef6-b164-aedf7881cbe3.pdf
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. Oepkes D, Devlieger R, Lopriore E, et al. Successful ultrasound-guided laser treatment of fetal hydrops caused by pulmonary sequestration. Ultrasound Obstet Gynecol 2007;29(4):457–459. doi:10.1002/uog.3984.
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. Lindenburg IT, Smits-Wintjens VE, van Klink JM, et al. Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study. Am J Obstet Gynecol 2012;206(2):141.e1–141.e8. doi:10.1016/j.ajog.2011.09.024.
. van Klink J, Koopman HM, Middeldorp JM, et al. Long-term neurodevelopmental outcome after selective feticide in monochorionic pregnancies. BJOG 2015;122(11):1517–1524. doi:10.1111/1471-0528.13490.
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