Standardization in fetal growth restriction
Beune, Irene
DOI:
10.33612/diss.156487314
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Publication date: 2021
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Beune, I. (2021). Standardization in fetal growth restriction: Progression by consensus. University of Groningen. https://doi.org/10.33612/diss.156487314
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Chapter
Building consensus and standards in fetal growth
restriction studies
SJ Gordijn
IM Beune
W Ganzevoort
Abstract
Fetal growth restriction is a pathologic condition in which the fetus fails to reach its biolog-ically based growth potential. There is inconsistency in terminology, definition, monitoring, and management, both in clinical practice and in the existing literature. This hampers inter-pretation and comparison of cohorts and studies. Standardization is essential.
With the lack of a golden standard, or the opportunity to come to empirical evidence, consensus procedures can help to establish standardization. Consensus procedures provide no new information but formulate an agreement (as second best in the absence of robust evidence) for clinical and/or research practice on the basis of existing data. Consensus agreements need to be updated when new evidence becomes available and can change over time.
In this chapter, we address the different issues that lack uniformity in FGR studies and management. Furthermore, we discuss several consensus methods and recent consensus procedures regarding fetal growth restriction.
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Introduction
Some essential issues exist in fetal growth restriction (FGR), both in published reports as well as in clinical practice. Most of these issues hinge around the fact that there is no golden standard for the definition of “FGR” or study process. In this manuscript, we aim to identify the issues that need to be considered when describing, quantifying, and studying FGR and how consensus-building strategies can be employed to improve knowledge.
The issues
FGR is a condition in which placental insufficiency results in diminished fetal growth, as the placenta cannot meet the needs of the baby for oxygen and nutrient supplies.(1, 2) This is often a stand-alone placental developmental disorder, but it may occur in the presence of chromosomal/syndromal abnormalities, infections, and other conditions.(3, 4) As growth is affected, the fetus remains smaller than it was genetically designed to be, but of note is that fetuses with high growth potential may reach weights that are within normal ranges and thus in current practice unnoticed, as they are only relatively small (“masked growth restriction”).
The terminology used in literature to classify fetuses that fail to achieve their biologically based growth potential is inconsistent and therefore confusing.(5) Historically, many terms such as dwarfism, intrauterine growth restriction/retardation, diminished fetal growth, starved fetus, small, underweighted, and so on have been used. A frequently used term is intrauterine growth restriction/retardation (IUGR), where selective IUGR (sIUGR) is used in cases of twin pregnancy.(6) This term does not appropriately reflect the actual pathology: intrauterine refers to a location and not to a person who is actually affected. The term retar-dation in IUGR suggests a delay in growth, with the potential of catch-up growth, something that is not observed in fetuses that have a limitation of growth owing to a pathological pro-cess. Inconsistency in terminology adds to communication problems between healthcare professionals on the topic and further uncertainties regarding the optimal management of such high-risk pregnancies. The term used in this chapter is FGR. This term describes the subject of concern, the fetus, and its failure to achieve the biological growth potential. We therefore suggest to adhere to this term in future research and also to use this term in selective FGR in twin pregnancies.
FGR is thought to affect approximately 10% of pregnancies, although any estimate is imper-fect in the absence of a golden standard. It would be simplistic to think that the 10% lightest babies (the definition for small for gestational age [SGA]) are growth restricted and that the cut-off for FGR is the 10th percentile on a growth chart. SGA is often used interchange-ably with FGR, although SGA is considered to be a principally different, not necessarily patho logical, condition. SGA is based on a statistical deviation of size from an often popu-lation-based reference.(7) FGR indicates that the fetus does not reach its optimal growth, and it is to a great extent independent of the absolute fetal weight. Even fetuses that are considered large in a population can be growth restricted if their growth potential was even higher (Fig. 1). As stated above, the incidence of FGR and SGA is both approximately 10%. Although they are not the same, there is overlap as FGR concentrates in SGA. It is estimated that in the small fetus group, the SGA group, usually defined as growth below the 10th per-centile (<p10), 60% is growth restricted and 40% is physiologically small.(8) The lower the growth as expressed in growth percentile, the higher the chance of pathology and thus FGR or susceptibility to problems after birth.(9) The challenge in current obstetrics is to differen-tiate the healthy SGA baby from the FGR baby and to define the FGR babies in the groups with appropriate for gestational age (AGA) or even large for gestational age (LGA) (Fig. 1). The risks of inaccurate differentiation of FGR within these different growth/weight groups are overtreatment of the healthy SGA and undertreatment of the FGR fetus with “normal” growth/weight.
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The importance in appropriately identifying FGR fetuses and babies is that the condition imposes evident risks. Before birth, stillbirth is an apparent risk, and after birth, babies are metabolically challenged and glucose metabolism is problematic. Appropriate identification leads to appropriate monitoring for these transitional processes. After birth, correct identi-fication will help in the adequate monitoring of neonates at risk for poor outcome, and, for example, prevent hypoglycemia in these subjects.
Diagnosis of FGR cannot be based on single biometric measurements, as growth is dynamic, not static, and more than one measurement is necessary to make a prospective determina-tion of (impaired) growth. Excepdetermina-tion is made when measurements are extreme: estimated fetal weight or fetal abdominal circumference (FAC) of <p3 or absent end diastolic flow (in early FGR) is considered to be sufficient to diagnose FGR irrespective of other measure-ments in time or biometric values(10) because this solitary measurement is predictive of bad outcome.(11) If a fetus grows congruently along a growth centile on the chart, the
Figure 1. Schematic representation of the possible overlap between FGR and SGA and between AGA and LGA
FGR Fetal growth restriction; SGA Small for gestational age; AGA Appropriate for gestational age; LGA Large for gestational age.
fetus is probably physiologically small and not growth restricted, even if it is below the 10th centile. If a fetus grows incongruently along the growth centiles on the chart, dropping from high to low, the fetus is likely to be growth restricted, even if it is above the 10th centile. To make a better determination of whether a fetus is growth restricted, several other indica-tors that are indicative of placental function may be used. Doppler flow velocity profiles in the umbilical, uterine, and middle cerebral arteries are widely used to determine high-resistance circulation that reflects placental insufficiency.(12-14) Moreover, experimentally, several placental serum markers are used, which reflect starvation or placental compen-satory trajectories that try to initiate better growth of the fetus.(15, 16) The most used markers are the placental growth factor and sFlt, but many other markers have been under investigation, such as IGF, hCG, and AFP, and none of these have been determined to be suf-ficiently accurate in indicating diminished growth for current practice at the moment. The identification of FGR is not uniform throughout gestational ages. In early gestational ages, almost all FGR fetuses will demonstrate abnormal smallness and accompanying symptoms such as hypertensive disorders and decreased movements (easy to diagnose and difficult to treat). In general, the early FGR occurs less often, but with graver consequences, as delivery of preterm babies will stop the intrauterine starvation but induce prematurity. In late preg-nancy, the pathology is less extreme and the symptoms less obvious (difficult to diagnose and easy to treat). Late FGR occurs more often and usually has less impact. Because of the large numbers of pregnancies, the overall impact on a population level is high, underlining the importance of adequate identification of fetuses and babies at risk.
It is important to consider not only the definition of the condition but also the reference by which size aberration has to be judged. Many growth centiles have been developed in different, more or less healthy, populations. The percentage of fetuses indicated to be SGA differs for different reference charts, and with the same measurement, up to 15% can remain undiscovered with the use of different charts.(17) If FGR is defined as a fetus that does not reach its individual growth potential, it is crucial to develop tools to compare the fetus with individualized growth trajectories. Customized charts that are currently available consider several characteristics that are known to affect fetal growth, such as maternal and/ or paternal height, BMI, and ethnic background.(18-20) This implies, on the one hand, that a smaller couple would get a smaller baby and that people of certain ethnic backgrounds would get smaller babies; on the other hand, bigger couples and couples from certain eth-nic backgrounds would get bigger babies. However, etheth-nic background is not easily under-stood and is multi-interpretable,(21) and it has been shown not to influence healthy fetal weight as much as the variation within populations.(22)
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Additionally, customization carries the risk of correction for a suboptimal, and possible pathological, situation (the parents may not be optimally grown themselves or are from a socio-economically challenged population).
Even if FGR is well defined and everybody uses the same growth centiles based on the perfect healthy population and we perform ultrasounds in every pregnant women regularly, we are not able to detect all SGA or FGR babies for the significant inter- and intraobserver variation of all ultrasound measurements. The individual available investigations have poor accuracy for detection. With a single ultrasound measurement, 50% of SGA cases are iden-tified. This is tripled by sequential measurements or by adding AC growth velocity analyses. (23)
The issues described above point to an important hiatus; the fact that there is no golden standard and measurements have their significant imperfections has led to a strong varia-tion in how populavaria-tions are described. To deal with this, many studies have fallen back to describe the population of interest only by the aberration of size, i.e., SGA. This is an imper-fection by itself. To reduce variation and more accurately define the population at risk, there is need for consensus on definitions and alignment of study designs.
Consensus and standardization
As pointed out above, every aspect of FGR studies can benefit from standardization. Com-parison of demographic characteristics of populations, including changes in height and weight, is only possible when agreed standard measurements are applied for every in-dividual, preferably at standard times. For accurate comparison of details regarding FGR studies, not only a definition of the condition but also standardized study protocol details would be helpful. No golden standard for FGR study protocols exists nor can they be de-veloped if every study investigates different aspects of FGR. However, a standard format to report important details in studies of prevention, monitoring, and treatment allows future comparison, and adherence to the standard format could improve reliability of studies. Such a set of details can be developed in a minimum reporting set (MRS), which states the minimum of baseline and process parameters that should be accounted for in a study protocol. Another important agreement can be made on a core outcome set (COS), which states the minimum outcomes to report in a study of that topic. COSs are developed so that a study is not restricted (it is a minimum set), but rather, any other important outcome of the study is also measured and reported. The minimum set results are used in comparing studies, even in individual patient data (IPD) analysis. Several initiatives support the use of COSs such as the CROWN initiative (the core outcomes In Women’s and Newborn Health
initiative), which is an international initiative led by journal editors to encourage the use of COSs in current research development (www.crown-initiative.org). Both MRS and COS can be developed by a group of experts with broad expertise in a specific area of research, who are asked to create a sensible list of items that they think is important. Although expert opinions are based on integrated evidence, these lists of items are not the absolute truth or the only possible perfect list and will not be applicable for every study. However, in general, studies regarding a particular topic can apply those lists and from then forward be compara-ble. Not only comparability but also quality of studies profit from these lists, as unimportant outcomes will not be published without the outcomes in the COS and important outcomes that do not reach significance will be reported, thereby reducing reporting bias.
How to come to consensus and standardization
Many consensus-building strategies are used in healthcare. Everyday decisions are built on consensus. Consenting to something does not necessarily mean that one fully agrees to it, it means there are no reasonable objections, and for several possible reasons, one decides to consent and conform. Consensus may come about informally, but there are formal strat-egies to achieve consensus. It is important to understand that formal consensus develop-ment is not a method to create new knowledge but makes the best use of already available information. A prerequisite to successful consensus is that there is no golden standard, that opinions are not diametrically opposed to each other in advance, and that participants are willing to change their opinion.(24)
Consensus in daily clinical practice
Consensus-seeking behavior is informal in everyday clinical practice when patient care is discussed between caregivers. Sometimes the actual given care is dictated by guide-lines, but mostly the team comes to a sensible monitoring and treatment strategy based on knowledge from variable sources. The group discussion and decision-making in these situations is a form of a consensus procedure, although it is prone to authoritative influ-ences and local culture and a wide range of options can be decided upon for that particular situation; there is a high situational variability in this state of uncertainty.(25) Healthcare team composition changes within and over days. This composition can result in different strategies for several reasons: people chose interventions with which they are most famil-iar; hence, a younger team may decide different than an older team.(25) A recently experi-enced adverse outcome in almost the same situation can result in another approach than that previously used, and when the “big boss” is present in the discussion, her/his strategy will probably be used. During group discussions, the major risk is that of noise (discussions that do not contribute to the strategy but distract attention from the basic of the
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not feel knowledgeable enough; therefore, they will most likely support the opinion of the highest acknowledged or ranked person in the room.
Expert consensus
Implicit consensus may also arise after an accepted authority publishes a view on a partic-ular situation. The scientific community may value this view as worthy of adhering to this new classification, definition, management algorithm, etc., and adopt it. A good example is the article by Gratacos, which describes classification and management of selective FGR of one of the two monochorionic twins.(26) It has thus been de facto accepted as guideline because of the obvious expertise of the author group and the sound argumentation.
Consensus by the Delphi method
The Delphi methodology taps in on the knowledge of a panel, or different panels with dif-ferent stakeholder groups. The participants receive feedback on the results of the previous round, and in subsequent iterative rounds, questions become more specific and precise to stimulate convergence of opinion.(27) Results are reported at the group level, in which one’s own individual responses are also usually provided, with guaranteed anonymity of subjects’ individual responses to others. This type of feedback takes away the influence of dominant individuals and group pressure. Panels may be fully anonymous, where the mem-bers are unaware who their fellow panel memmem-bers are, or they may be semi-anonymous, where panel participants are aware who their fellow panel members are. The advantage of a semi anonymous panel is that members can appreciate the quality of the panel. This is mainly useful in (healthcare) professional expert panels and less useful in other stakeholder groups such as lay experts.
The Delphi procedure has originally been developed by RAND corporation in the 1950s for convergence of opinion using informed intuitive judgment in forecasting of technology, but not for healthcare. The developers state that the Delphi methodology derives its impor-tance from the realization that (policy) decisions are based on individual expectations and interpretations rather than a theoretical model, and even when a formal mathematical model is available, the applicability of this model is subject to interpretations.(28-30) Of key importance is the selection of the expert panel (or panels if different stakeholder groups are involved). In the original descriptions, frequency distributions to identify patterns of agree-ment are exerted, and it was explicitly stated that participants should not meet each other in face-to-face meetings to prevent unwanted influence from socially dominant individuals. (30-32) Delphi procedures are being widely applied in healthcare.
appointment/agree-ment to accept the results as a substitute until a better paradigm arises. It may be useful to repeat procedures after several years for new or additional evidence that is published or when after prospectively using the former product of consensus turns out to be useless.
Consensus by nominal group technique (NGT)
Another consensus approach, which includes a face-to-face meeting, is the nominal group technique (NGT). This was also not developed for healthcare but as a group process ap-proach for practicing administrators charged with a program development task.(33) The essential feature of the nominal group technique is that people are in a well-organized, structured, face-to-face meeting with a robust facilitator. Each participant has equal oppor-tunity to state their ideas (anonymously) and has an equal vote. Convergence is reached by summarizing initial ideas and discussion of different options and voting. The process starts with a phase of (silent) idea generation in which the panel members write down as many options they can think of in a set time frame (originally 30 min). In the second phase, all ideas are collected in a round-robin format, i.e., one idea per person at a time is collect-ed and listcollect-ed by the facilitator, without discussion, which is ongoing until all options are collected. During the collection of ideas, panel members can think of new ideas and wait their (new) turn to share with the group. In the third phase, the ideas are then presented and clarified by the people who suggested them; similar ideas are congregated. All options are to be explained sufficiently to ensure understanding by all and to be able to come to in-formed decision-making in the ranking phase. The study team needs to hold on to a pre-de-cided method to come to consensus, for example, ranking with a cut-off of the first ten, or level of agreement above a certain percentage.
In practice, often panel members are provided with a number of recording cards, usually five. One should choose five options from the main list accordingly. After that the options are ranked with a pre-specified scoring system, usually 5 points for the most important option to 1 point for the least important option. The scores for the individual panel mem-bers are confidential. In the final phase, the scores for every option are collected and the hierarchical list of importance is presented and discussed.(25, 33-35) The NGT is suitable for small groups (mostly around 4–9 participants), and for larger groups, the group is split into smaller groups with a facilitator for every group.(33, 36)
Several adaptations have been made to this technique, such as providing pre-meeting infor-mation to generate ideas, re-ranking, and discussion until no further discussion points.
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In the nominal group technique, the facilitator has an important role in ensuring that the process is as neutral as possible and no criticism should be allowed. This is essential to rule out dominancy and make sure everybody can speak up and to limit bias.(25, 29, 33)
Combined consensus strategies
Today, often consensus meetings are organized at the end of a Delphi procedure to come to final agreement. The RAND Appropriate Method is a combination of evidence and expert opinion. In this method, a systematic literature review precedes a questionnaire, and after that, a panel meeting is organized. It is developed to detect when the experts agree rather than to come to consensus.(29) This method is adapted to be used as a face-to-face meet-ing at the end of a Delphi method to come to consensus.(37, 38) Others combine Delphi and NGT to come to final consensus.(39)
Consensus and standardization in FGR studies
At the moment, several efforts are made to standardize and harmonize several aspects of FGR (studies) in an international collaboration with the aim to come to standards in defining and reporting of figures and studies of FGR. The research line started with the very basis of the FGR: to overcome the inconsistencies in its definition. Internationally recognized FGR experts were approached to complete an e-Delphi procedure, which resulted in a consen-sus definition.(10) In this definition of FGR, early FGR (<32 weeks) and late FGR (≥32 weeks of gestation) are discriminated and functional parameters are included in addition to the traditionally used biometrical parameters (Table 1). The same procedure was held in a group of neonatologists specialized in growth restriction in the newborn (GRN). The need for this definition stems from the limited diagnostic efficacy of antenatal care, and it should be able to identify the growth-restricted newborn in the absence of an antenatal diagno-sis.(40) A third procedure was conducted on the definition of FGR in twin pregnancies, for monochorionic (MC) and dichorionic (DC) twins separately, as the origin of biometric mea-surement differences between them can be very different. The issue of sFGR in MC twins versus exclusion of twin–twin transfusion syndrome (TTTS) and the issue of whether to use twin-specific reference charts have been studied.(41) The definition formally adopts the Gratacos classification in the monitoring scheme of these pregnancies.(26) Another proce-dure is in preparation for the definition of growth restriction in stillborn babies, as those babies cannot be plotted on the normal neonatal population weight charts for gestational age.(42) All consensus definitions comprise parameters that can diagnose FGR solitary at a strict cut-off, and at a less strict cut-off, a combination of several parameters should be abnormal before diagnosis can be made. Moreover, a MRS for FGR studies has been
devel-oped for structure of future study protocols and cohorts.(41) Finally, at present, a Delphi procedure is initiated within the COMET initiative (www.comet-initiative.org) to come to a COS in FGR studies.(43) After deciding on what should be reported (outcomes), it has to be decided how these items are measured and the reference values to be used. Prinsen et al. have written a protocol on the development of measurement instruments in which they describe the selection of possible measurement instruments by systematic reviews and another consensus approach to come to the ultimate measurement instrument.(44)
Summary
The lack of a golden standard of FGR causes inconsistency in terminology, definition, mon-itoring, and management. SGA is often used interchangeably with FGR, but it is a statistical definition and describes a principally different, not necessarily pathological, condition.
Standardization is essential for comparison of cohorts and studies. Consensus procedures can help to establish uniformity, in the absence of empirical evidence. A consensus-based agreement is not an absolute truth and may change when new evidence arises. However, standardization, even in the absence of evidence, or with suboptimal cut-offs, is better than disparity. Strategies to build consensus are expert consensus, the Delphi method, nominal group technique, or combinations of these procedures.
Currently, several attempts are undertaken in an international collaboration to standardize definitions and study protocols for FGR. A consensus definition for FGR has been developed, as well as a definition for growth restriction in the newborn. A procedure has been con-ducted to define sFGR in both DC and MC twins and to define guidelines in monitoring and management. Another procedure planned is for defining growth restriction in the stillborn. Furthermore, a minimum reporting set (MRS) in FGR studies has been developed. More-over, a Delphi procedure is initiated to develop a core outcome set (COS).
Adherence in FGR studies and clinical practice to these consensus definitions and guidelines is the only way to facilitate comparison. The consensus definitions should be prospectively tested to evaluate their accuracy, and new evidence should be integrated in the course of time.
3 Table 1 Consensus-based definitions for early and late FGR.
Early FGR: gestational age <32 weeks, in the absence of congenital anomalies AC/EFW
<p3 or AEDF in the umbilical artery
Or
1. AC/EFW <p10 combined with
2. PI in the uterine artery >p95 and/or
3. PI in the umbilical artery >p95
Late FGR: gestational age ≥32 weeks, in the absence of congenital anomalies AC/EFW <p3 Or
At least 2 out of 3 of the following 1. AC/EFW <p10
2. Crossing centiles of more than 2 quartiles on growth centilesa 3. CPR <p5
Practice points
• SGA is principally different from FGR
• The challenge in current obstetrics is to differentiate the healthy SGA baby from the FGR baby and to define the FGR babies
in the groups with appropriate for gestational age (AGA) or even large for gestational age(LGA)
• The risks of inaccurate differentiation of FGR within these different growth/weight groups are overtreatment of the healthy SGA and undertreatment of the FGR fetus with “normal” growth/weight. • Consensus-based standards are relative to time (current evidence)
and consulted with experts. Effort should be made to come to max imum supported agreements; therefore, one should care
fully select the stakeholders.
• Standardization, even in the absence of evidence, or with subopti mal cut-offs, is better than disparity.
• Adhering to consensus definitions improves the possibilities for research now and in the future.
• In FGR studies, effort is made to standardize inclusions to FGR studies (FGR definition, and twins definition) and study protocols (MRS and COS).
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References
1. Mifsud W, Sebire NJ. Placental pathology in early-onset and late-onset fetal growth restriction. Fetal Diagn Ther. 2014;36(2):117-28.
2. Kingdom J, Huppertz B, Seaward G, Kaufmann P. Development of the placental villous tree and its consequences for fetal growth. Eur J Obstet Gynecol
Reprod Biol. 2000;92(1):35-43.
3. Snijders RJ, Sherrod C, Gosden CM, Nicolaides KH. Fetal growth retardation: associated malformations and chromosomal abnormalities. Am J Obstet Gynecol. 1993;168(2):547-55.
4. Yamamoto R, Ishii K, Shimada M, Hayashi S, Hidaka N, Nakayama M, Mitsuda N. Significance of maternal screening for toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus infection in cases of fetal growth restriction. J
Obstet Gynaecol Res. 2013;39(3):653-7.
5. American College of O, Gynecologists. ACOG Practice bulletin no. 134: fetal growth restriction. Obstet Gynecol. 2013;121(5):1122-33.
6. Unterscheider J, Daly S, Geary MP, Kennelly MM, McAuliffe FM, O’Donoghue K, Hunter A, Morrison JJ, Burke G, Dicker P, Tully EC, Malone FD. Definition and manage
ment of fetal growth restriction: a survey of contemporary attitudes. Eur J Obstet Gynecol Reprod Biol. 2014;174:41-5.
7. Lausman A, Kingdom J, Maternal Fetal Medicine C. Intrauterine growth restriction: screening, diagnosis, and management. J Obstet Gynaecol Can. 2013;35(8):741-8.
8. Figueras F, Gratacos E. An integrated approach to fetal growth restriction. Best Pract Res Clin Obstet Gynaecol. 2017;38:48-58.
9. Vasak B, Koenen SV, Koster MP, Hukkelhoven CW, Franx A, Hanson MA, Visser GH. Human fetal growth is constrained below optimal for perinatal survival. Ultrasound Obstet Gynecol. 2015;45(2):162-7.
10. Gordijn SJ, Beune IM, Thilaganathan B, Papageorghiou A, Baschat AA, Baker PN, Silver RM, Wynia K, Ganzevoort W. Consensus definition of fetal growth restriction: a Delphi procedure. Ultrasound Obstet Gynecol. 2016;48(3):333-9. 11. Figueras F, Eixarch E, Meler E, Iraola A, Figueras J, Puerto B, Gratacos E.
Small-for-gestational-age fetuses with normal umbilical artery Doppler have suboptimal perinatal and neurodevelopmental outcome. Eur J Obstet Gynecol Reprod Biol. 2008;136(1):34-8.
12. Baschat AA, Gembruch U, Harman CR. The sequence of changes in Doppler and biophysical parameters as severe fetal growth restriction worsens. Ultra
sound Obstet Gynecol. 2001;18(6):571-7.
13. Hecher K, Bilardo CM, Stigter RH, Ville Y, Hackeloer BJ, Kok HJ, Senat MV, Visser GH. Monitoring of fetuses with intrauterine growth restriction: a longitudinal study. Ultrasound Obstet Gynecol. 2001;18(6):564-70.
14. Bilardo CM, Wolf H, Stigter RH, Ville Y, Baez E, Visser GH, Hecher K. Relationship between monitoring parameters and perinatal outcome in severe, early intrauterine growth restriction. Ultrasound Obstet Gynecol. 2004;23(2):119-25. 15. Benton SJ, Hu Y, Xie F, Kupfer K, Lee SW, Magee LA, von Dadelszen P. Can pla
cental growth factor in maternal circulation identify fetuses with placental intrauterine growth restriction? Am J Obstet Gynecol. 2012;206(2):163 e1-7.
16. Conde-Agudelo A, Papageorghiou AT, Kennedy SH, Villar J. Novel biomarkers for predicting intrauterine growth restriction: a systematic review and me
ta-analysis. BJOG. 2013;120(6):681-94.
17. Salomon LJ, Bernard JP, Duyme M, Buvat I, Ville Y. The impact of choice of Obstet Gynecol. 2005;25(6):559-65.
18. Clausson B, Gardosi J, Francis A, Cnattingius S. Perinatal outcome in SGA births defined by customised versus population-based birthweight standards. BJOG. 2001;108(8):830-4.
19. de Jong CL, Gardosi J, Dekker GA, Colenbrander GJ, van Geijn HP. Application of a customised birthweight standard in the assessment of perinatal
outcome in a high risk population. Br J Obstet Gynaecol. 1998;105(5):531-5. 20. Gardosi J, Chang A, Kalyan B, Sahota D, Symonds EM. Customised antenatal
growth charts. Lancet. 1992;339(8788):283-7.
21. Lockie E, McCarthy EA, Hui L, Churilov L, Walker SP. Feasibility of using self-reported ethnicity in pregnancy according to the gestation-relat ed optimal weight classification: a cross-sectional study. BJOG. 2018;125(6):704-9.
22. Papageorghiou AT, Ohuma EO, Altman DG, Todros T, Cheikh Ismail L, Lambert A, Jaffer YA, Bertino E, Gravett MG, Purwar M, Noble JA, Pang R, Victora CG, Barros FC, Carvalho M, Salomon LJ, Bhutta ZA, Kennedy SH, Villar J, Inter national F, Newborn Growth Consortium for the 21st C. International stan dards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. Lancet. 2014;384(9946):869-79.
23. Sovio U, White IR, Dacey A, Pasupathy D, Smith GCS. Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study. Lancet. 2015;386(10008):2089-97.
24. Fletcher SW. Whither scientific deliberation in health policy recommen dations? Alice in the Wonderland of breast-cancer screening. N Engl J Med. 1997;336(16):1180-3.
25. Murphy MK, Black NA, Lamping DL, McKee CM, Sanderson CF, Askham J, Marteau T. Consensus development methods, and their use in clinical guide line development. Health Technol Assess. 1998;2(3):i-iv, 1-88.
26. Gratacos E, Lewi L, Munoz B, Acosta-Rojas R, Hernandez-Andrade E, Martinez JM, Carreras E, Deprest J. A classification system for selective intrauterine
growth restriction in monochorionic pregnancies according to umbilical artery Doppler flow in the smaller twin. Ultrasound Obstet Gynecol. 2007;30(1):28-34.
27. McKenna HP. The Delphi technique: a worthwhile research approach for nursing? J Adv Nurs. 1994;19(6):1221-5.
28. Dalkey N, Helmer O. An experimental application of the Delphi method to the use of experts. Manag Sci. 1963;9(3):458-67.
29. Fitch K, Bernstein Sj, Aguilar MD, Burnand B, LaCalle jR, Lazaro P, van het
Loo M, McDonnell J, Vader JP, Kahan Jp. The RAND/UCLA appropriateness method User’s manual. RAND Corporation, Santa Monica, CA, USA. 2001.
3
31. Loughlin KG, Moore LF. Using Delphi to achieve congruent objectives and activities in a pediatrics department. J Med Educ. 1979;54(2):101-6. 32. Whitman NI. The committee meeting alternative. Using the Delphi tech
nique. J Nurs Adm. 1990;20(7-8):30-6.
33. Delbecq AL, Van de Ven AH. A group process model for problem identifica tion and program planning. J Appl Behav Sci. 1971;7(4):466-92.
34. McMillan SS, King M, Tully MP. How to use the nominal group and Delphi techniques. Int J Clin Pharm. 2016;38(3):655-62.
35. Lennon R, Glasper A, Carpenter D. Nominal Group Technique: its utilisation to explore the rewards and challenges of becoming a mental health nurse, prior to the introduction of the all graduate nursing curriculum in England. Southampton, UK 2012 [Available from: http://www.southampton.ac.uk/as sets/centresresearch/documents/wphs/NominalGroupTechnique.pdf.
36. McMillan SS, Kelly F, Sav A, Kendall E, King MA, Whitty JA, Wheeler AJ. Using the Nominal Group Technique: how to analyse across multiple groups. Health Services and Outcomes Research Methodology 2014;14:92–108.
37. To T, Guttmann A, Lougheed MD, Gershon AS, Dell SD, Stanbrook MB, Wang C, McLimont S, Vasilevska-Ristovska J, Crighton EJ, Fisman DN. Evidence-based performance indicators of primary care for asthma: a modified RAND Appropriateness Method. Int J Qual Health Care. 2010;22(6):476-85.
38. Duffy JM, van ‘t Hooft J, Gale C, Brown M, Grobman W, Fitzpatrick R, Karu manchi SA, Lucas N, Magee L, Mol B, Stark M, Thangaratinam S, Wilson M, von Dadelszen P, Williamson P, Khan KS, Ziebland S, McManus RJ, Interna tional Collaboration to Harmonise Outcomes for P-e. A protocol for developing, disseminating, and implementing a core outcome set for pre-eclampsia. Pregnancy Hypertens. 2016;6(4):274-8.
39. Gerbens LA, Boyce AE, Wall D, Barbarot S, de Booij RJ, Deleuran M, Middelkamp-Hup MA, Roberts A, Vestergaard C, Weidinger S, Apfelbacher CJ,
Irvine AD, Schmitt J, Williamson PR, Spuls PI, Flohr C. TREatment of
ATopic eczema (TREAT) Registry Taskforce: protocol for an international Delphi exercise to identify a core set of domains and domain items for national atopic eczema registries. Trials. 2017;18(1):87.
40. Beune IM, Bloomfield FH, Ganzevoort W, Embleton ND, Rozance PJ, van Wassenaer-Leemhu is AG, Wynia K, Gordijn SJ. Consensus Based Definition of
Growth Restriction in the Newborn. J Pediatr. 2018;196:71-6 e1.
41. Khalil A, Beune I, Hecher K, Wynia K, Ganzevoort W, Reed K, Lewi L, Oepkes D, Gratacos E, Thilaganathan B, Gordijn SJ. Consensus definition and essential reporting parameters of selective fetal growth restriction in twin preg nancy: a Delphi procedure. Ultrasound Obstet Gynecol. 2019;53(1):47-54. 42. Sebire NJ. Detection of fetal growth restriction at autopsy in non-anomalous
stillborn infants. Ultrasound Obstet Gynecol. 2014;43(3):241-4.
43. Williamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Brookes ST,
Clarke M, Gargon E, Gorst S, Harman N, Kirkham JJ, McNair A, Prinsen CAC, Schmitt J, Terwee CB, Young B. The COMET Handbook: version 1.0. Trials. 2017;18(Suppl 3):280. 44. Prinsen CA, Vohra S, Rose MR, Boers M, Tugwell P, Clarke M, Williamson PR,
Terwee CB. How to select outcome measurement instruments for outcomes included in a “Core Outcome Set” - a practical guideline. Trials. 2016;17(1):449.
