Original Paper Received: June 29, 2016 Accepted after revision: November 25, 2016 Published online: March 17, 2017 Fetal Diagn Ther 2017;42:210–217 DOI: 10.1159/000455024 Specialty-Based Variation in Applying Maternal-Fetal Surgery Trial Evidence Ryan M. Antiel a–c Alan W. Flake a Mark P. Johnson a Nahla Khalek a Natalie E. Rintoul a John D. Lantos e Farr A. Curlin f Jon C. Tilburt b, d Chris Feudtner a a University of Pennsylvania Perelman School of Medicine and Children’s Hospital of Philadelphia, Philadelphia, PA, Biomedical Ethics Program, c Department of General Surgery, and d Division of General Internal Medicine, Mayo Clinic, Rochester, MN, e Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO, and f Trent Center for Bioethics, Humanities, and History of Medicine, Duke University, Durham, NC, USA Keywords Maternal-fetal surgery · Myelomeningocele · Spina bifida · Prenatal diagnosis · Physician attitudes Abstract Introduction: The Management of Myelomeningocele Study (MOMS) compared prenatal with postnatal surgery for fetal myelomeningocele (MMC). We sought to understand how subspecialists interpreted the trial results and whether their practice has changed. Materials and Methods: Cross-sectional, mailed survey of 1,200 randomly selected maternalfetal medicine (MFM) physicians, neonatologists, and pediatric surgeons. Results: Of 1,176 eligible physicians, 670 (57%) responded. Compared to postnatal closure, 33% viewed prenatal closure as “very favorable” and 60% as “somewhat favorable.” Most physicians reported being more likely to recommend prenatal surgery (69%), while 28% were less likely to recommend pregnancy termination. In multivariable analysis, neonatologists were more likely to report prenatal closure as “very favorable” (OR 1.6; 95% CI: 1.03–2.5). Pediatric surgeons and neonatologists were more © 2017 S. Karger AG, Basel E-Mail firstname.lastname@example.org www.karger.com/fdt likely to recommend prenatal closure (OR 2.1; 95% CI: 1.3– 3.3, and OR 2.9; 95% CI: 1.8–4.6) and less likely to recommend termination (OR 3.8; 95% CI: 2.2–6.7, and OR 4.7; 95% CI: 2.7– 8.1). In addition, physicians with a higher tolerance for prematurity were more likely to report prenatal closure as “very favorable” (OR 1.02; 95% CI: 1.00–1.05). Discussion: In light of the MOMS trial, the vast majority of pediatric subspecialists and MFMs view prenatal MMC closure favorably. These attitudes vary by specialty and risk tolerance. © 2017 S. Karger AG, Basel Introduction Myelomeningocele (MMC) represents the first nonlethal prenatal diagnosis that can be managed with maternal-fetal surgery. MMC is characterized by protrusion of the spinal cord through the open vertebrae into the amniotic fluid, frequently resulting in variable degrees of lifelong disability. In the recent past, three options were available: postnatal closure, postnatal palliative care, or termination of pregnancy. Now a fourth option exists. Ryan M. Antiel, MD University of Pennsylvania Perelman School of Medicine Blockley Hall, 423 Guardian Drive, Floor 14 Philadelphia, PA 19104 (USA) E-Mail antiel @ mail.med.upenn.edu Downloaded by: Vanderbilt University Library 184.108.40.206 - 10/29/2017 2:16:35 AM b Surgeons can now perform maternal-fetal surgery and close the MMC prenatally. This specific open maternalfetal surgery aims to mitigate damage from chronic chemical and mechanical insults in utero. Early results from nonrandomized studies suggested that prenatal closure could minimize or reverse hindbrain herniation and decrease the need for cerebrospinal fluid shunt for hydrocephalus [1–5]. In February 2003, with the endorsement of the American College of Obstetrics and Gynecology  and others [7–9], the NIH sponsored a prospective randomized clinical trial to test the efficacy and safety of prenatal surgical treatment. The Management of Myelomeningocele Study (MOMS) was conducted at the Children’s Hospital of Philadelphia, Vanderbilt University, and the University of California, San Francisco . Prenatal closure resulted in a decrease in shunt placement (40 vs. 82%), a decrease in the presence of hindbrain herniation (64 vs. 96%), as well as an increase in the ability to walk independently without orthotics upon exam (42 vs. 21%) at 30 months of age. There were, however, significant maternal and fetal risks. The prenatal surgery group experienced an increased incidence of chorioamniotic membrane separation (26 vs. 0%), spontaneous membrane rupture (46 vs. 8%), need for blood transfusion at cesarean delivery (9 vs. 1%), and area of uterine dehiscence at hysterotomy (10 vs. 0%). These complications led to a greater incidence of prematurity in the prenatal surgery group (13% delivered at less than 30 weeks’ gestation vs. 0%). Given the tradeoffs revealed by the trial results between the potential neonatal benefits and maternal and neonatal risks and the uncertainty of outcomes for any given pregnant woman and fetus, some physicians urged caution before widespread adoption of this approach . As such, MOMS illustrates some of the well-known limitations of clinical trials that measure multiple outcomes. Patient decisions inevitably reflect preferences and values, along with high-quality evidence . In the case of prenatally diagnosed MMC, the decision-making process typically occurs in a stepwise manner, with obstetricians and maternal-fetal medicine (MFM) physicians first communicating with and counseling the pregnant woman regarding a range of options. Neonatologists and pediatric surgeons are often involved later in the multidisciplinary process of prenatal evaluation and counseling. We sought to clarify how the results of MOMS influenced the opinions and potential recommendations of these three professional specialties involved in the care of pregnant women and fetuses with MMC. We hypothe- sized that MFM physicians, with their focus on the health and well-being of the maternal-fetal dyad, would be less persuaded by the MOMS results. In comparison, neonatologists and pediatric surgeons, with their focus on the care of neonates, would be more favorably influenced by the trial results. Since the publication of the MOMS trial results, no empirical studies have been conducted to describe how these subspecialists have interpreted and applied the trial findings. Applying Maternal-Fetal Surgery Trial Evidence Fetal Diagn Ther 2017;42:210–217 DOI: 10.1159/000455024 Materials and Methods Study Participants and Data Collection In the spring of 2015, we mailed a confidential, self-administered, 11-page, 32-item questionnaire titled “Emerging Issues in Maternal-Fetal Surgery” to a random sample of 1,200 practicing US physicians. The sample included 400 MFMs, 400 neonatologists, and 400 pediatric surgeons. These physicians were randomly selected from member lists of the Society for Maternal-Fetal Medicine, the American Academy of Pediatrics Section on Perinatal Pediatrics, and the American Academy of Pediatrics Section on Surgery, respectively. Using the Tailored Design Method , up to three separate mailings were sent, the first mailing including a USD 20 bill. This study was reviewed and deemed exempt by the Mayo Clinic Institutional Review Board. 211 Downloaded by: Vanderbilt University Library 220.127.116.11 - 10/29/2017 2:16:35 AM Survey Instrument We reviewed the literature, consulted with content experts, conducted physician interviews at five maternal-fetal centers, formulated questions, and then conducted cognitive interviews in which draft survey instruments were administered to specialty colleagues whose feedback was used to revise questions further. The primary outcome variables were physicians’ responses to a series of questions asked after participants reviewed a table of results from the MOMS trial (see Appendix A). First, physicians were asked, “In your opinion, how favorable is prenatal surgery for MMC, compared to postnatal surgery?” Response categories were “very favorable,” “somewhat favorable,” “somewhat unfavorable,” “unfavorable,” or “not sure.” Next, physicians were asked, “In light of these results, please tell us whether your attitude changed regarding any of the options that are available to pregnant women with a newly diagnosed fetal MMC. Do these results make you more or less likely to recommend: termination of pregnancy, open uterine prenatal surgery, and postnatal closure (no fetal surgery)?” Response categories for each were “less likely,” “no change,” and “more likely.” Given that the results of the MOMS trial may not be reproducible in some centers, we asked physicians to assume their center offered prenatal surgery and that they were reviewing their institution’s 5-year outcome data. We then asked physicians to indicate the highest complication rate of three outcomes associated with prenatal surgery that they would consider acceptable. Outcomes included: rate of perinatal mortality, rate of prematurity (less than 30 weeks), and rate of uterine dehiscence. We also examined physician demographic characteristics (age, sex, region, specialty, and years in practice) and practice setting type. Results Of the 1,200 potential respondents, 24 (2%) could not be contacted. Of the remaining participants, 670 returned completed surveys for a response rate of 57%. Response rates did not differ significantly by specialty (MFM, 54%; neonatology, 57%; pediatric surgery, 60%; p = 0.2). The characteristics of the respondents are shown in Table 1. Subspecialty Interpretation of Evidence and Influence on Clinical Recommendations As seen in Table 2, the majority of our cohort believe that prenatal closure for MMC (compared to postnatal closure) was favorable (33% “very favorable,” 60% “somewhat favorable”). In light of the MOMS trial results, 69% of respondents reported that they are more likely to recommend prenatal closure, and only 4% indicated they were less likely to recommend prenatal closure. In addition, 38% of all respondents reported they would be less likely to recommend postnatal closure in light of trial results, and only 4% would be more likely (58% no change). The MOMS trial appeared to influence some physicians’ attitudes about termination of pregnancy: 28% of respondents reported that they were now less likely to recommend termination (71% reported no change). A third of neonatologists and pediatric surgeons indicated that they are now less likely to recommend termination (36% and 32%, respectively), whereas 13% of MFM specialists reported being now less likely to recommend termination. Risk Tolerance As seen in Table 3, physician-reported median acceptable complication rates were quite similar to the complication rates reported in the MOMS trial for perinatal mortality (5 vs. 3%, respectively), gestational age at birth <30 weeks (15 vs. 13%, respectively), and uterine dehiscence (10 vs. 10%, respectively). The highest acceptable rates of complications by specialty are reported in Ta212 Fetal Diagn Ther 2017;42:210–217 DOI: 10.1159/000455024 Table 1. Characteristics of the 670 US physicians who responded to the survey Characteristic Response Specialty Maternal-fetal medicine specialist Neonatologist Pediatric surgeon Female sex Age <50 years ≥50 years Years in practice, mean (SD), years Race or ethnic group White or Caucasian Asian Black or African American Other Region Midwest Northeast South West Practice setting type Solo, private Group, private Institutional, private Academic Other Affiliation with fetal center Location (fetal care affiliates only) General hospital Women’s/women and infant hospital Children’s hospital Freestanding clinic or outpatient facility Other 208/388 (54) 228/397 (57) 234/391 (60) 245/659 (37) 256/653 (39) 397/653 (61) 18 (11) 523/664 (79) 88/664 (13) 27/664 (4) 26/664 (4) 168/670 (25) 141/670 (21) 235/670 (35) 126/670 (19) 21/663 (3) 152/663 (23) 95/663 (14) 345/663 (52) 50/663 (8) 402/660 (61) 107/376 (29) 99/376 (26) 132/376 (35) 28/376 (7) 10/376 (3) Data are given as n (%), except where indicated. Percentages may not total 100 because of rounding. ble 3. MFM specialists were willing to accept slightly higher average rates of perinatal mortality than neonatologists or pediatric surgeons (7.8% compared to 6.4 and 5.8%, respectively, p < 0.001). Multivariate Analysis In multivariate logistic regression models controlling for age, years in practice, region, and practice setting (Table 4), self-reported affiliation with a fetal center was not significantly associated with responses to the relevant items. Male physicians were more likely to recommend open maternal-fetal surgery (74 vs. 66%; odds ratio [OR] 1.69; 95% confidence interval [CI]: 1.08–2.64) and were more likely to report that they would not recommend terAntiel/Flake/Johnson/Khalek/Rintoul/ Lantos/Curlin/Tilburt/Feudtner Downloaded by: Vanderbilt University Library 18.104.22.168 - 10/29/2017 2:16:35 AM Data Management and Analysis Responses were double entered and imported into SAS version 9.3. We used the American Association for Public Opinion Research RR2 response rate definition . We used descriptive statistics and logistic regression to assess associations between physician specialty and characteristics and their attitudes toward prenatal MMC closure in light of the MOMS trial results. When distributions allowed, we dichotomized results for ease of presentation. The Kruskal-Wallis test was used to compare the self-reported highest acceptable complication rates among specialties. Statistical inferences were based on 2-tailed tests with significance set at p < 0.05. Table 2. Physicians’ opinions about the MOMS trial results All physicians MFMs Neonatologists Considering the known risks and benefits, how favorable is open prenatal surgery for MMC? Very favorable 219 (33) 62 (31) 86 (39) Somewhat favorable 398 (60) 127 (64) 124 (56) Somewhat unfavorable 25 (4) 10 (5) 5 (2) Unfavorable 7 (1) 1 (1) 5 (2) Compared to before the MOMS trial, are you now more or less likely to recommend: Termination of pregnancy Less likely 182 (28) 26 (13) No change 468 (71) 175 (86) More likely 8 (1) 2 (1) Prenatal MMC closure Less likely 23 (4) 8 (4) No change 185 (28) 81 (40) More likely 454 (69) 115 (56) Postnatal MMC closure (no fetal surgery) Less likely 250 (38) 69 (34) No change 382 (58) 123 (61) More likely 25 (4) 10 (5) Surgeons 71 (31) 147 (64) 10 (4) 1 (1) 81 (36) 139 (62) 4 (2) 75 (32) 154 (67) 2 (1) 9 (4) 51 (23) 165 (73) 6 (3) 53 (23) 174 (75) 92 (41) 124 (55) 8 (4) 89 (39) 135 (58) 7 (3) Data are given as n (%). Percentages may not total 100 because of rounding. MFMs, maternal-fetal medicine specialists; MMC, myelomeningocele. Table 3. Physicians’ risk tolerance Survey item Group All physicians p value MFMs Neonatologists Surgeons What is the highest complication rate associated with open prenatal surgery that you would consider acceptable? Rate of perinatal death, % Mean (SD) 6.6 (8.6) 7.8 (9.67) 6.4 (8.1) 5.8 (8.0) Median (IQR) 5 (3–5) 5 (3–10) 5 (2–5) 4 (2–5) Rate of prematurity (less than 30 weeks), % Mean (SD) 16.8 (11.0) 16.8 (9.6) 17.1 (12.3) 16.5 (10.7) Median (IQR) 15 (10–20) 15 (10–20) 15 (10–20) 15 (10–20) Rate of uterine dehiscence, % Mean (SD) 9.4 (8.1) 8.6 (7.9) 10.3 (9.1) 9.0 (7.0) Median (IQR) 10 (5–10) 10 (5–10) 10 (5–10) 10 (5–10) <0.001 0.47 0.20 mination of pregnancy (30 vs. 24%; OR 1.91; 95% CI: 1.15–3.16). Neonatologists, compared to MFMs, were more likely to report prenatal closure as “very favorable” (OR 1.64; 95% CI: 1.00–2.70). Compared to MFMs, pediatric surgeons and neonatologists were more likely to recommend prenatal closure (OR 2.11; 95% CI: 1.27–3.49, and OR 2.57; 95% CI: 1.55–4.25, respectively) and were less likely to recommend termination (OR 4.09; 95% CI: 2.17–7.72, and OR 4.40; 95% CI: 2.36–8.21, respectively). The acceptable rates of complications were also significantly associated with how a physician interpreted Applying Maternal-Fetal Surgery Trial Evidence Fetal Diagn Ther 2017;42:210–217 DOI: 10.1159/000455024 213 Downloaded by: Vanderbilt University Library 22.214.171.124 - 10/29/2017 2:16:35 AM p values are for the comparison between specialty groups and were calculated with the use of the Kruskal-Wallis test. MFMs, maternal-fetal medicine specialists. Table 4. Physicians’ opinions about the MOMS trial results according to physician characteristics Age <50 years ≥50 years Sex Female Male Affiliation with fetal center Yes No Specialty MFM Surgeon Neonatologist Risk tolerance Rate of perinatal death Rate of prematurity Rate of uterine dehiscence Interpretation of MOMS results Recommendations after MOMS trial Prenatal surgery for MMC (very favorable vs. somewhat favorable) Less likely to recommend termination of pregnancy (vs. no change) More likely to recommend open prenatal closure (vs. no change) Less likely to recommend postnatal closure (vs. no change) 1.0 (referent) 0.73 (0.37–1.45) 1.0 (referent) 0.67 (0.31–1.44) 1.0 (referent) 1.05 (0.52–2.12) 1.0 (referent) 1.67 (0.86–3.24) 1.0 (referent) 1.35 (0.86–2.10) 1.0 (referent) 1.91 (1.15–3.16)* 1.0 (referent) 1.69 (1.08–2.64)* 1.0 (referent) 0.94 (0.61–1.44) 1.0 (referent) 0.85 (0.57–1.29) 1.0 (referent) 0.93 (0.58–1.47) 1.0 (referent) 0.93 (0.61–1.44) 1.0 (referent) 1.15 (0.77–1.73) 1.0 (referent) 0.98 (0.59–1.66) 1.64 (1.00–2.70)* 1.0 (referent) 4.09 (2.17–7.72)*** 4.40 (2.36–8.21)*** 1.0 (referent) 2.11 (1.27–3.49)** 2.57 (1.55–4.25)*** 1.0 (referent) 1.30 (0.79–2.12) 1.43 (0.88–2.32) 0.99 (0.96–1.02) 1.02 (1.00–1.05)* 1.01 (0.99–1.03) 0.96 (0.93–0.99)* 1.05 (1.02–1.07)*** 1.01 (0.98–1.04) 0.97 (0.94–1.00) 1.05 (1.02–1.08)** 1.02 (0.99–1.05) 0.98 (0.95–1.01) 1.02 (0.99–1.04) 1.03 (1.00–1.06)* Data are given as odds ratios (95% confidence intervals). Odds ratios are from multivariate logistic regression, with adjustment for years in practice, region of practice, practice setting type, and ethnicity/race. MMC, myelomeningocele; MFM, maternal-fetal medicine specialist. * p < 0.05, ** p < 0.01, *** p < 0.001. Discussion Most physicians among these relevant specialties believe the results from the MOMS trial are “somewhat” or “very” favorable. In light of the trial results, the majority of surveyed subspecialists report that they have shifted to now being more likely to recommend prenatal MMC closure, with the greatest shift occurring among neonatologists and 214 Fetal Diagn Ther 2017;42:210–217 DOI: 10.1159/000455024 pediatric surgeons. The majority of physicians report that the MOMS trial results have not changed their likelihood of recommending termination of pregnancy; however, a significant minority (28%) report that they are now less likely to recommend termination. MFM physicians were less likely to have changed their recommendations compared to the pediatric subspecialists, likely reflecting MFMs’ commitment to nondirective or neutral counseling . The interpretation and influence of the MOMS trial evidence appears to vary by respondent characteristics. Compared to MFMs, neonatologists interpret the MOMS trial results more favorably. Compared to MFMs, neonatologists and pediatric surgeons are more likely to recommend prenatal MMC surgery, and both are now less likely to recommend termination of pregnancy. In addition, physician tolerance for risk of complications was also associated with trial interpretation and influence, even while controlling for specialty. And finally, female physicians were less likely to change their recommendations about prenatal closure or termination of pregnancy than were male physicians, potentially because maternal-fetal surgery directly affects the reproductive health of women. Antiel/Flake/Johnson/Khalek/Rintoul/ Lantos/Curlin/Tilburt/Feudtner Downloaded by: Vanderbilt University Library 126.96.36.199 - 10/29/2017 2:16:35 AM and applied MOMS trial results. Physicians who would tolerate a high rate of prematurity were more likely to view prenatal closure as “very favorable” (OR 1.02; 95% CI: 1.00–1.05), more likely to recommend prenatal surgery (OR 1.05; 95% CI: 1.02–1.08), and more likely to not recommend termination (OR 1.05; 95% CI: 1.02–1.07). Physicians who would tolerate higher rates of perinatal death did not change in their recommendations for termination following the trial (OR 0.96; 95% CI: 0.93–0.99). Finally, physicians who reported a higher tolerance for uterine dehiscence were less likely to recommend postnatal surgery (OR 1.03; 95% CI: 1.00–1.06). tions of pregnancy . A European center recently reported that 76% of prenatal diagnoses of spina bifida resulted in termination, and the authors found that requests were not correlated with the severity of disease . The results of the MOMS trial may modify this number as perceptions surrounding open maternal-fetal surgery change. Our results suggest, however, that the impact of the MOMS trial results on decisions surrounding termination may depend upon who conveys those results to the pregnant woman. MFMs are more likely than neonatologists or pediatric surgeons to discuss termination of pregnancy as an acceptable option for pregnancy management in addition to prenatal surgery for MMC. Patients and families may be affected, directly or indirectly, by the professional and personal factors that shape how respondents replied to the questions posed by this survey. Specifically, prenatal counseling may be influenced by provider specialty as well as risk tolerance for various associated complications. This study highlights the need for balanced consultation, full disclosure, and an open dialogue with families to optimize shared decisionmaking and mitigate unconscious bias. Ideally, all physicians would engage in explicit and open discussions about the potential risks and benefits to both the pregnant woman and to her fetus . As pediatric subspecialists participate in the care discussion for women who elect prenatal surgery for MMC, they must be sensitive to, and mindful of, issues surrounding the pregnant woman and her family. Furthermore, while some of the individual centers involved in the MOMS trial have replicated the trial results following the closure of the study , it is crucial for less experienced centers to be transparent with their outcomes. Our findings should be interpreted with four main limitations kept in mind. First, in order to capture attitudinal changes, we used similar language to previously published studies, including the term “recommend” . While we cannot determine whether respondents’ reports of changes in their attitudes correspond to changes in their clinical practices, including specific recommendations, ample evidence exists that attitudes towards medical and surgical interventions influence how physicians counsel patients [35–37]. Second, while we identified specific hypothesized associations in this cross-sectional study, other factors may also be associated with how physicians interpret trial data and form their subsequent recommendations, including professional society statements. Previous analysis of the positions of the ethics committees of the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists Applying Maternal-Fetal Surgery Trial Evidence Fetal Diagn Ther 2017;42:210–217 DOI: 10.1159/000455024 215 Downloaded by: Vanderbilt University Library 188.8.131.52 - 10/29/2017 2:16:35 AM This study suggests that professional identity and specialty role and culture influence the interpretation and application of trial evidence in maternal-fetal surgery. Such a finding is consistent with other studies of how physicians and surgeons interpret and apply medical science [15–17]. Specialty bias and differing interpretations of evidence lead to divergent treatment recommendations and ongoing debates for conditions ranging from prostate cancer [18, 19] to menopausal hormone therapy [20–22] to treatment for sciatica [23–25]. Different specialty groups view certain ethical aspects of maternal-fetal surgery differently . In the specific case of the interpretation of the MOMS trial, a concern for maternal-fetal health, both during the affected pregnancy and from the perspective of future reproductive health, continues to prevail among MFMs about prenatal surgery for MMC. Historically, the care of pregnant women carrying fetuses with anomalies was exclusively the domain of obstetrics and MFM. With the rapid evolution of prenatal diagnosis and fetal therapy, pediatric subspecialists are now participating in multidisciplinary care planning for those patients electing open maternal-fetal surgery. Traditionally, pediatricians and pediatric surgeons are trained to focus on the well-being of the neonate, whereas MFMs are uniquely positioned in that they routinely consider both the well-being of the pregnant woman and fetus. In this specific context, these roles have become more fluid as the fetus has become a “patient” [27–29]. For most pregnancies, the well-being of the pregnant woman and the fetus are fully aligned. In the context of prenatal surgery for MMC, a divergence can occur, as the pregnant woman assumes increased risks for the prospect of improving her future child’s well-being. While MFMs are also dedicated to improving neonatal outcomes, they must simultaneously manage and balance the risks to the pregnant woman. Furthermore, MFMs encounter pregnant women earlier in the process of medical evaluation and decision-making, and the profession strongly advocates for discussing all possible management options, including termination, in a nondirective manner. This specific aspect of maternal-fetal care plan discussion may not be applicable by the time pediatric subspecialists enter the conversation. At the same time, however, the majority of both MFMs and pediatric subspecialists believe that a pediatric consult should take place prior to decision to terminate a pregnancy with spina bifida (77 vs. 82%, respectively) . A systematic review of studies published between 1994 and 2004 estimated that in the US, approximately 43% of prenatal diagnoses of spina bifida resulted in termina- found subtle differences between the societies concerning maternal-fetal conflicts and interventions . Third, even with the high response rate to this survey, the attitudes of physicians who did not respond to the survey may differ from those who did respond. Fourth, not all physicians who responded to the survey are directly involved in caring for patients and families who elect maternal-fetal surgery. Also, we were unable to survey all types of providers who may be involved in maternal-fetal counseling including pediatric neurosurgeons or genetic counselors. We designed the sample frame of our study to reflect the broader obstetric and pediatric professional interpretation of the MOMS trial results and recommendations as the field of maternal-fetal surgery is expanding, with seventeen centers in the US now offering or performing open prenatal surgery for spina bifida. Notwithstanding these limitations, this study indicates that the majority of subspecialists view the MOMS trial results favorably, yet it also notes that the degree to which physicians’ potential recommendations were influenced by the MOMS results varied across specialties and by risk tolerance. Prenatal maternal-fetal surgery for spina bifida is demonstrative of how the use of evidence-based medicine necessarily requires consideration of trade-offs between maternal health, future reproductive health, fetal health, and the potential well-being of the future child . The results of this study can be considered as professional societies draft and update guidelines for counseling. Since individual physician characteristics influence the interpretation of trial outcome data, physicians should be self-aware about their own values and risk tolerance that are operative in their professional interpretation and discussion of treatment options. Acknowledgment We thank Sarah M. Jenkins, MS, from the Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA, for her help with the statistical analysis. Disclosure Statement The authors declare that they have no conflicts of interest. Funding Sources Supported by a grant from the Greenwall Foundation. Appendix A The recent Management of Myelomeningocele Study (MOMS) was a randomized controlled trial that compared prenatal and postnatal surgery for myelomeningocele (MMC). Results are below: Fetal or neonatal outcome Perinatal death Prematurity <30 weeks At 12 months Placement of shunt Hindbrain herniation At 30 months Walking independently on exam Maternal outcome Maternal death Chorioamniotic separation Spontaneous membrane rupture Uterine dehiscence Blood transfusion at delivery 216 Prenatal surgery (n = 78) Postnatal surgery (n = 80) p value 2 (3%) 10 (13%) 2 (2%) 0 1.00 <0.001 31 (40%) 45/70 (64%) 66 (82%) 66/69 (96%) <0.001 <0.001 26/62 (42%) 14/67 (21%) 0.01 0 20 (26%) 36 (46%) 8/76 (10%) 7 (9%) 0 0 6 (8%) NA 1 (1%) Fetal Diagn Ther 2017;42:210–217 DOI: 10.1159/000455024 <0.001 <0.001 0.03 Antiel/Flake/Johnson/Khalek/Rintoul/ Lantos/Curlin/Tilburt/Feudtner Downloaded by: Vanderbilt University Library 184.108.40.206 - 10/29/2017 2:16:35 AM Outcome References Applying Maternal-Fetal Surgery Trial Evidence 15 Perez EA: Perceptions of prognosis, treatment, and treatment impact on prognosis in non-small cell lung cancer. Chest 1998; 114: 593–604. 16 Seidman AD: Sequential single-agent chemotherapy for metastatic breast cancer: therapeutic nihilism or realism? J Clin Oncol 2003; 21:577–579. 17 Ellerbeck EF, Jencks SF, Radford MJ, et al: Quality of care for Medicare patients with acute myocardial infarction. A four-state pilot study from the Cooperative Cardiovascular Project. JAMA 1995;273:1509–1514. 18 Sommers BD, Beard CJ, D’Amico AV, Kaplan I, Richie JP, Zeckhauser RJ: Predictors of patient preferences and treatment choices for localized prostate cancer. Cancer 2008; 113: 2058–2067. 19 Kim SP, Gross CP, Nguyen PY, et al: Specialty bias in treatment recommendations and quality of life among radiation oncologists and urologists for localized prostate cancer. Prostate Cancer Prostatic Dis 2014;17:163–169. 20 Goldman N: New evidence rekindles the hormone therapy debate. J Fam Plann Reprod Health Care 2010;36:61–64. 21 Manson JE, Chlebowski RT, Stefanick ML, et al: Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 2013;310:1353–1368. 22 Manson JE, Kaunitz AM: Menopause management – getting clinical care back on track. N Engl J Med 2016;374:803–806. 23 Peul WC, van Houwelingen HC, van den Hout WB, et al: Surgery versus prolonged conservative treatment for sciatica. N Engl J Med 2007;356:2245–2256. 24 Jacobs WC, van Tulder M, Arts M, et al: Surgery versus conservative management of sciatica due to a lumbar herniated disc: a systematic review. Eur Spine J 2011;20:513–522. 25 Lewis RA, Williams NH, Sutton AJ, et al: Comparative clinical effectiveness of management strategies for sciatica: systematic review and network meta-analyses. Spine J 2015; 15: 1461–1477. 26 Brown SD, Lyerly AD, Little MO, Lantos JD: Paediatrics-based fetal care: unanswered ethical questions. Acta Paediatrica 2008;97:1617– 1619. 27 Chervenak FA, McCullough LB: The fetus as a patient: an essential ethical concept for maternal-fetal medicine. J Matern Fetal Med 1996;5:115–119. 28 McCullough LB, Chervenak FA: A critical analysis of the concept and discourse of “unborn child”. Am J Bioeth 2008;8:34–39. 29 Lyerly AD, Little MO, Faden RR: A critique of the “fetus as patient”. Am J Bioeth 2008;8:42– 44, discussion W4–W6. 30 Brown SD, Feudtner C, Truog RD: Prenatal decision-making for myelomeningocele: can we minimize bias and variability? Pediatrics 2015;136:409–411. 31 Johnson CY, Honein MA, Dana Flanders W, Howards PP, Oakley GP Jr, Rasmussen SA: Pregnancy termination following prenatal diagnosis of anencephaly or spina bifida: a systematic review of the literature. Birth Defects Res A Clin Mol Teratol 2012;94:857–863. 32 Ovaere C, Eggink A, Richter J, et al: Prenatal diagnosis and patient preferences in patients with neural tube defects around the advent of fetal surgery in Belgium and Holland. Fetal Diagn Ther 2015;37:226–234. 33 Moldenhauer JS, Soni S, Rintoul NE, et al: Fetal myelomeningocele repair: the post-MOMS experience at the Children’s Hospital of Philadelphia. Fetal Diagn Ther 2015;37:235–240. 34 Brown SD, Ecker JL, Ward JRM, et al: Prenatally diagnosed fetal conditions in the age of fetal care: does who counsels matter? Am J Obstet Gynecol 2012;206:409.e1–11. 35 Curlin FA, Lawrence RE, Chin MH, Lantos JD: Religion, conscience, and controversial clinical practices. N Engl J Med 2007; 356: 593–600. 36 Tucker EB, McKenzie F, Farrow V, Raglan G, Schulkin J: A national survey of obstetricians’ attitudes toward and practice of periviable intervention. J Perinatol 2015;35:338–343. 37 Edmonds BT, McKenzie F, Hendrix KS, Perkins SM, Zimet GD: The influence of resuscitation preferences on obstetrical management of periviable deliveries. J Perinatol 2015; 35: 161–166. 38 Brown SD, Truog RD, Johnson JA, Ecker JL: Do differences in the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists positions on the ethics of maternal-fetal interventions reflect subtly divergent professional sensitivities to pregnant women and fetuses? Pediatrics 2006;117:1382–1387. Fetal Diagn Ther 2017;42:210–217 DOI: 10.1159/000455024 217 Downloaded by: Vanderbilt University Library 220.127.116.11 - 10/29/2017 2:16:35 AM 1 Meuli M, Meuli-Simmen C, Hutchins GM, Yingling CD: In utero surgery rescues neurological function at birth in sheep with spina bifida. Nat Med 1995;1:342–347. 2 Adzick NS, Sutton LN, Crombleholme TM, Flake AW: Successful fetal surgery for spina bifida. Lancet 1998;352:1675–1676. 3 Tulipan N, Hernanz-Schulman M, Bruner JP: Reduced hindbrain herniation after intrauterine myelomeningocele repair: a report of four cases. Pediatr Neurosurg 1998; 29: 274– 278. 4 Bruner JP, Tulipan N, Paschall RL, et al: Fetal surgery for myelomeningocele and the incidence of shunt-dependent hydrocephalus. JAMA 1999;282:1819–1825. 5 Sutton LN, Adzick NS, Bilaniuk LT, Johnson MP, Crombleholme TM, Flake AW: Improvement in hindbrain herniation demonstrated by serial fetal magnetic resonance imaging following fetal surgery for myelomeningocele. JAMA 1999;282:1826–1831. 6 American College of Obstetricians and Gynecologists: Fetal Surgery for Open Neural Tube Defects. ACOG committee opinion No. 252. Washington, DC: American College of Obstetricians and Gynecologists, 2001. 7 Simpson JL: Fetal surgery for myelomeningocele: promise, progress, and problems. JAMA 1999;282:1873–1874. 8 Lyerly AD, Cefalo RC, Socol M, Fogarty L, Sugarman J: Attitudes of maternal-fetal specialists concerning maternal-fetal surgery. Am J Obstet Gynecol 2001;185:1052–1058. 9 Hirose S, Farmer DL, Albanese CT: Fetal surgery for myelomeningocele. Curr Opin Obstet Gynecol 2001;13:215–222. 10 Adzick NS, Thom EA, Spong CY, et al: A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 2011;364:993–1004. 11 Simpson JL, Greene MF: Fetal surgery for myelomeningocele? N Engl J Med 2011; 364: 1076–1077. 12 Lantos JD, Lauderdale DS: Preterm Babies, Fetal Patients, and Childbearing Choices. Cambridge, The MIT Press, 2015. 13 Dillman D, Smyth J, Christian L: Internet, Mail, and Mixed-Mode Surveys: The Tailored Design Method, 3rd ed. Hoboken, John Wiley & Sons, 2009. 14 American Association for Public Opinion Research: Standard Definitions: Final Dispositions of Case Codes and Outcome Rates for Surveys, 7th ed. Lenexa, AAPOR, 2011.