1. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Katherine E. Hartmann, MD, PhD Lucius E. Burch Chair, Obstetrics and Gynecology Deputy Director, Institute for Medicine and Public Health Director, Vanderbilt Evidence-based Practice Center Evidence Limited to Inform Decisions about Maternal-Fetal Surgery

2. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Technical Brief Intent Summarizing the state of the field including:  Content of the research  Access to fetal surgery  Training of providers  Ethical aspects  Coverage of procedures  Ongoing studies

3. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Selection of target conditions  Cardiac malformations  Congenital diaphragmatic hernia  Myelomeningocele  Obstructive uropathy  Sacrococcygeal teratoma  Thoracic lesions (Congenital Pulmonary Airway Malformations)  Twin-twin transfusion syndrome

4. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Review Team & Expert Panel Selection  Fetal sonographers/echocardiographers  Maternal-fetal medicine specialists  Perinatal geneticists  Pediatric surgeons  “Fetal” surgeons  Neonatologists  Biomedical ethicists  Generalists prenatal care providers  Familiarity with perinatal hospice

5. VANDERBILT EVIDENCE-BASED PRACTICE CENTER State of the Evidence Methods  PubMed, MEDLINE (no date limits)  English, ≥ 2 cases, condition of interest, fetal intervention, training information, outcomes including quality of life (for mother or fetus)  Included RCT, cohorts with comparison, case-control, and case series

6. VANDERBILT EVIDENCE-BASED PRACTICE CENTER State of the Evidence Review Methods  Dual review of abstracts  Dual review of articles  Extraction of descriptive data into standardized forms: – study design and setting – fetal and maternal inclusion criteria – training of providers – outcomes measured – length of follow up

7. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Disposition of the Literature  Abstracts: 1382  Articles: 620  Relevant studies: 166  Study designs RCTS: 3 Cohort studies: 47 Case series: 116  Studies from US: 74

8. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Cardiac Malformations Studies (n=9) Pulmonary atresia with intact ventricular septum—2 case series Aortic stenosis—8 case series Hypoplastic left heart syndrome and intact atrial septum—3 case series State of the Science 90 pregnancies in literature 1 study provided infant outcomes beyond hospital stay Maternal inclusion criteria poorly reported No data on long term survival or neurologic outcomes

9. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Congenital Diaphragmatic Hernia Studies (n=21) 1 RCT 3 prospective cohorts 5 retrospective cohorts 2 prospective case series 10 retrospective case series State of the Science Fetal inclusion criteria well- reported; 9 of 21 reported maternal criteria Few measured outcomes beyond hospital stay (8/21) Longest reported infant follow up: 24-48 months Long term maternal outcomes addressed in 2 studies

10. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Cardiac Diaphragmatic hernia Myelomening- ocele Obstructive uropathy Sacrococcygeal teratoma Thoracic lesions Twin-twin transfusion Total Literature (n=9)(n=21)(n=11)(n=25)(n=5)(n=11)(n=84)(n=166) U.S.6121114462174 European2904134968 Asian000201 5 8 Other 100501 916 Overview

11. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Cardiac Diaphragmatic hernia Myelomening- ocele Obstructive uropathy Sacrococcygeal teratoma Thoracic lesions Twin-twin transfusion Total Literature Study Type Case series9124141373116 Retro. cohort0558476 36 Prospective cohort0323013 11 Randomized clinical trial 0100002 3 Overview

12. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Cardiac Diaphragmatic hernia Myelomening- ocele Obstructive uropathy Sacrococcygeal teratoma Thoracic lesions Twin-twin transfusions Total Literature Last infant assessment Birth 6319242247 ≤ 6 mos 1922021935 > 6 to ≤ 12 mos 01410118 > 12 mos 28411341951 Unknown 0002002325 Overview

13. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Child Developmental Status Any Maternal Outcomes Cardiac malformations 0/9 4/9 CDH 7/21 11/21 Myelomeningocele 3/11 4/11 Obstructive uropathy 5/25 2/25 Sacrococcygeal teratoma 0 3/5 Thoracic lesions 2/11 1/11 Twin-twin transfusion syndrome 13/844/84 Outcomes reported

14. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Challenges for the field include: Rare conditions with no method to consolidate new cases Cases accrue slowly - innovations change the benefit equation Clinical and research classifications of fetal anomalies vary Spontaneous regression/stabilization occurs Prognosis cannot be determined with high accuracy Changes in the spectrum of disease reduces comparability to prior natural history studies of anticipated outcomes Intervention techniques change rapidly Higher SES patients are over-represented Regionalization of care needs consideration No formal plan for certified training programs exists

15. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Strategies to Reduce Evidence Gaps Continue to develop consensus operational definitions Enhance attention to common data elements Use valid and reliable tools for outcomes Support platforms for cooperative data sharing Use analyses to help define equipoise for trials Develop new methods for funding and cost sharing Establish a consistent set of ethical standards for research in the field

16. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Challenges for Technical Brief Process  Content of the research: organizing classification, defining families, resisting urge to cross into outcomes  Access to fetal surgery: identifying pool of experts - able to establish via direct communication with those who publish  Training of providers: identifying sites - able to establish  Ethical aspects: balancing priorities for the report  Coverage: identifying accurate, available sources  Ongoing studies: documenting trials more achievable than other studies

17. VANDERBILT EVIDENCE-BASED PRACTICE CENTER Technical Brief Conclusions Limited RCT evidence Literature dominated by case series (70% of studies) Lack of clearly described maternal inclusion criteria and long term follow-up for infant or mother Limited outcomes reported: Literature not typical level of quality of studies or aggregate strength of evidence sufficient to guide care