Testing the applicability and additional value of a consultation round after the consensus meeting in the development of two core outcome sets.

OBJECTIVES: Test applicability and additional value of a consultation round after the consensus meeting in the development of core outcome sets (COSs). STUDY DESIGN AND SETTING: In two COS procedures (Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints (COSGROVE) and Definition and Core Outcomes on Hyperemesis Gravida (DCOHG)) that followed the Core Outcome Measures in Effectiveness Trials methodology, the first round of convergence to consensus among stakeholder groups in an online Delphi procedure was followed by a face-to-face consensus meeting during which a COS was formulated. We subsequently presented the COS to the online panel in a consultation round to confirm that the online panel agreed with the choices made at the consensus meeting, defined as 80% agreement. PARTICIPANTS: In the COSGROVE Study, there were eight stakeholder groups, and 83 out of 107 participants completed the consultation round. In the DCOHG Study, there were four stakeholder groups, and 96 out of 125 completed the consultation round. INTERVENTIONS: Adding a consultation round after completing a modified Delphi method with a consensus meeting. RESULTS: There was a level of agreement of 81% and 84%, respectively, in the consultation round of both procedures. This was above the preset level of agreement. The consultation round yielded additional suggestions to refine COS formulation in one of the studies. CONCLUSION: Our study shows that in two procedures, the online expert panel agreed with the participants of the consensus meeting in these procedures, lending validity to existing COS methodology. Future studies could evaluate whether bringing back the COS for confirmation after the consensus meeting could potentially increase the uptake of the final COS.

Consensus Definition of Fetal Growth Restriction in Intrauterine Fetal Death: A Delphi Procedure.

CONTEXT.­: Fetal growth restriction is a risk factor for intrauterine fetal death. Currently, definitions of fetal growth restriction in stillborns are heterogeneous. OBJECTIVES.­: To develop a consensus definition for fetal growth restriction retrospectively diagnosed at fetal autopsy in intrauterine fetal death. DESIGN.­: A modified online Delphi survey in an international panel of experts in perinatal pathology, with feedback at group level and exclusion of nonresponders. The survey scoped all possible variables with an open question. Variables suggested by 2 or more experts were scored on a 5-point Likert scale. In subsequent rounds, inclusion of variables and thresholds were determined with a 70% level of agreement. In the final rounds, participants selected the consensus algorithm. RESULTS.­: Fifty-two experts participated in the first round; 88% (46 of 52) completed all rounds. The consensus definition included antenatal clinical diagnosis of fetal growth restriction OR a birth weight lower than third percentile OR at least 5 of 10 contributory variables (risk factors in the clinical antenatal history: birth weight lower than 10th percentile, body weight at time of autopsy lower than 10th percentile, brain weight lower than 10th percentile, foot length lower than 10th percentile, liver weight lower than 10th percentile, placental weight lower than 10th percentile, brain weight to liver weight ratio higher than 4, placental weight to birth weight ratio higher than 90th percentile, histologic or gross features of placental insufficiency/malperfusion). There was no consensus on some aspects, including how to correct for interval between fetal death and delivery. CONCLUSIONS.­: A consensus-based definition of fetal growth restriction in fetal death was determined with utility to improve management and outcomes of subsequent pregnancies.

Early-onset fetal growth restriction: A systematic review on mortality and morbidity.

INTRODUCTION: Severe early-onset fetal growth restriction is an obstetric condition with significant risks of perinatal mortality, major and minor neonatal morbidity, and long-term health sequelae. The prognosis of a fetus is influenced by the extent of prematurity and fetal weight. Clinical care is individually adjusted. In literature, survival rates vary and studies often only include live-born neonates with missing rates of antenatal death. This systematic review aims to summarize the literature on mortality and morbidity. MATERIAL AND METHODS: A broad literature search was conducted in OVID MEDLINE from 2000 to 26 April 2019 to identify studies on fetal growth restriction and perinatal death. Studies were excluded when all included children were born before 2000 because (neonatal) health care has considerably improved since this period. Studies were included that described fetal growth restriction diagnosed before 32 weeks of gestation and antenatal mortality and neonatal mortality and/or morbidity as outcome. Quality of evidence was rated with the GRADE instrument. RESULTS: Of the 2604 publications identified, 25 studies, reporting 2895 pregnancies, were included in the systematic review. Overall risk of bias in most studies was judged as low. The quality of evidence was generally rated as very low to moderate, except for 3 large well-designed randomized controlled trials. When combining all data on mortality, in 355 of 2895 pregnancies (12%) the fetus died antenatally, 192 died in the neonatal period (8% of live-born neonates) and 2347 (81% of all pregnancies) children survived. Of the neonatal morbidities recorded, respiratory distress syndrome (34% of the live-born neonates), retinopathy of prematurity (13%) and sepsis (30%) were most common. Of 476 children that underwent neurodevelopmental assessment, 58 (12% of surviving children, 9% of all pregnancies) suffered from cognitive impairment and/or cerebral palsy. CONCLUSIONS: When combining the data of 25 included studies, survival in fetal growth restriction pregnancies, diagnosed before 32 weeks of gestation, was 81%. Neurodevelopmental impairment was assessed in a minority of surviving children. Individual prognostic counseling on the basis of these results is hampered by differences in patient and pregnancy characteristics within the included patient groups.

A Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints: the COSGROVE study.

BACKGROUND: Fetal growth restriction refers to a fetus that does not reach its genetically predetermined growth potential. It is well-recognized that growth-restricted fetuses are at increased risk of both short- and long-term adverse outcomes. Systematic evaluation of the evidence from clinical trials of fetal growth restriction is often difficult because of variation in the outcomes that are measured and reported. The development of core outcome sets for fetal growth restriction studies would enable future trials to measure similar meaningful outcomes. OBJECTIVE: The purpose of this study was to develop core outcome sets for trials of prevention or treatment of fetal growth restriction. STUDY DESIGN: This was a Delphi consensus study. A comprehensive literature review was conducted to identify outcomes that were reported in studies of prevention or treatment of fetal growth restriction. All outcomes were presented for prioritization to key stakeholders (135 healthcare providers, 68 researchers/academics, and 35 members of the public) in 3 rounds of online Delphi surveys. A priori consensus criteria were used to reach agreement on the final outcomes for inclusion in the core outcome set at a face-to-face meeting with 5 healthcare providers, 5 researchers/academics, and 6 maternity service users. RESULTS: In total, 22 outcomes were included in the final core outcome set. These outcomes were grouped under 4 domains: maternal (n=4), fetal (n=1), neonatal (n=12), and childhood (n=5). CONCLUSION: The Core Outcome Set for the prevention and treatment of fetal GROwth restriction: deVeloping Endpoints study identified a large number of potentially relevant outcomes and then reached consensus on those factors that, as a minimum, should be measured and reported in all future trials of prevention or treatment of fetal growth restriction. This will enable future trials to measure similar meaningful outcomes and to ensure that findings from different studies can be compared and combined.

Core Outcome Set for GROwth restriction: deVeloping Endpoints (COSGROVE).

BACKGROUND: Foetal growth restriction (FGR) refers to a foetus that does not reach its genetically predetermined growth potential. It is well recognised that growth-restricted foetuses are at increased risk of stillbirth, foetal compromise, early neonatal death and neonatal morbidity. Later in life, they are prone to health problems, including increased risk of cardiovascular diseases and neurodevelopmental disorders. Interventions for preventing and treating FGR have been studied in many trials, but evidence is often difficult to synthesise and compare because of differences in the selection and definition of outcomes. To enable future trials to measure similar, meaningful outcomes, we are developing two core outcome sets (COS) - one for prevention and the other for treatment of FGR. METHODS: We will review the literature to identify previously reported outcomes. An international panel of relevant stakeholders who have experience of FGR (parent or carer of a baby that was growth restricted, health professional involved in the care of mothers and babies affected by FGR, a person with expertise in FGR research) will rate the importance of each of those outcomes in a series of three sequential online rounds of a Delphi study. Participants will be able to add items to the proposed list in round 1. A final face-to-face consensus meeting will be held with representatives of each stakeholder group at which a final list of outcomes for inclusion in the COS will be agreed. DISCUSSION: The development of COSs in FGR will ensure the collection and reporting of a minimum dataset agreed by stakeholder consensus and will reduce inconsistencies in the reporting of outcomes across relevant trials. Such standardisation in the reporting of outcomes will improve synthesis of evidence and generalisability of knowledge in the future by reducing heterogeneity in outcomes between trials and thus improve the results of systematic reviews and meta-analyses. Ultimately, we hope that the COSs will lead to an improvement in the quality of evidence-based clinical practice, enhance patient care, and improve the quality and consistency of research. TRIAL REGISTRATION: Not applicable. This study is registered in the Core Outcome Measures for Effectiveness (COMET) database.

Consensus Based Definition of Growth Restriction in the Newborn.

OBJECTIVE: To develop a consensus definition of growth restriction in the newborn that can be used clinically to identify newborn infants at risk and in research to harmonize reporting and definition in the current absence of a gold standard. STUDY DESIGN: An international panel of pediatric leaders in the field of neonatal growth were invited to participate in an electronic Delphi procedure using standardized methods and predefined consensus rules. Responses were fed back at group-level and the list of participants was provided. Nonresponders were excluded from subsequent rounds. In the first round, variables were scored on a 5-point Likert scale; in subsequent rounds, inclusion of variables and cut-offs were determined with a 70% level of agreement. In the final round participants selected the ultimate algorithm. RESULTS: In total, 57 experts participated in the first round; 79% completed the procedure. Consensus was reached on the following definition: birth weight less than the third percentile, or 3 out of the following: birth weight <10th percentile; head circumference <10th percentile; length <10th percentile; prenatal diagnosis of fetal growth restriction; and maternal pregnancy information. CONCLUSIONS: Consensus was reached on a definition for growth restriction in the newborn. This definition recognizes that infants with birth weights <10th percentile may not be growth restricted and that infants with birth weights >10th percentile can be growth restricted. This definition can be adopted in clinical practice and in clinical trials to better focus on newborns at risk, and is complementary to the previously determined definition of fetal growth restriction.

Building consensus and standards in fetal growth restriction studies.

Fetal growth restriction is a pathologic condition in which the fetus fails to reach its biologically based growth potential. There is inconsistency in terminology, definition, monitoring, and management, both in clinical practice and in the existing literature. This hampers interpretation 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.

Prediction of recurrence of hypertensive disorders of pregnancy in the term period, a retrospective cohort study.

OBJECTIVES: To assess the recurrence risk of term hypertensive disease of pregnancy and to determine which potential risk factors are predictive of recurrence. STUDY DESIGN: We performed a retrospective cohort study in two secondary and one tertiary care hospitals in the Netherlands. We identified women with a hypertensive disorder in the index pregnancy and delivery after 37weeks of gestation between January 2000 and December 2002. Data were extracted from medical files and women were approached for additional information on subsequent pregnancies. Adverse outcome was defined as recurrence of a hypertensive disorder in the next subsequent pregnancy. MAIN OUTCOME MEASURES: The absolute risk of recurrence and a prediction model containing demographic and clinical factors predictive of recurrence. RESULTS: We identified 638 women for potential inclusion, of whom 503 could be contacted. Of these women, 312 (62%) had a subsequent pregnancy. Hypertensive disorders recurred in 120 (38%, 95% CI 33-44) women, of whom 15 (5%, 95% CI 3-7) delivered preterm. Women undergoing recurrence were more at risk to develop chronic hypertension after pregnancy (35% versus 16%, OR 2.8, 95% CI 1.5-5.3). Body mass index, non-White European origin, chronic hypertension, maximum diastolic blood pressure, no use of anticonvulsive medication and interpregnancy interval were predictors for recurrence. CONCLUSIONS: Women with hypertensive disorders and term delivery have a substantial chance of recurrence, but a small risk of preterm delivery. A number of predictors for recurrence could be identified and women with a recurrence more often developed chronic hypertension.