Dispelling Myths about Antenatal TAPS: A Call for Action for Routine MCA-PSV Doppler Screening in the United States

Reviewer Comment

Authors’ Response

The authors are presenting a review of literature in support of   screening for twin anemia polycythemia sequence starting at 16 weeks in   monochorionic diamniotic twins. The manuscript is highly opinionated on   certain aspects supported some of the studies. The article does not   systematically address each questions with scientific rigor- a systematic   review or meta-analysis of existing literature. Therefore, it is a very good   letter to editor or an opinion, but lacks scientific merit to consider as a   original article.

It does not address the concerns of the critiques- the reference   standards in the studies, weaknesses in the original studies, variability in   definition of disease, and treatment effects on the TAPS.

In response to concerns about 1) the opinionated nature of   the manuscript; and, 2) the lack of scientific rigor, we appreciate insights   into ways in which the topic under examination could be developed into a   systematic review or meta-analysis of existing literature.  And, while   such approaches may be a subsequent examination for our team or others   tackling the gaps in clinical practice in regard to antenatal TAPS screening,   it is essential that deeply embedded assumptions and practices in the U.S.   are described in detail and critically examined from theoretical and   pragmatic perspectives.  That is, current gaps in antenatal screening   processes are due, in part, to misinterpretation or misuse of existing   literature, as well as, a lack of consideration for the significant progress   in research and clinical practice that has been detailed in the selected   literature that could yield a standard of care.  Because clinical   guidelines have been published that are counter to those valid studies we   have identified in this manuscript, addressing this issue through a critical   theoretical analysis is essential for prompting clinicians and readers to   re-visit those guidelines through future research, i.e., the meta-analysis   you have suggested.  To start with a meta-analysis will likely impair   the call to action, as such research may be exposed to the same fate as those   TAPS projects that are underutilized or ignored.  What we have provided   is an argumentative review, which by definition, is a selective examination   of literature to support or refute arguments, deeply embedded assumptions or   philosophical problems, which, in this case, have led to guidelines and   practices that negatively impact the welfare of our patient   populations.  This is our duty as researchers, clinicians, and   ethicists. In terms of scientific rigor, the approaches to this paper follow   the philosophical traditions of theoretical analysis, which is an accepted   methodology in bioethics and the social sciences that intersect with medical   research methods.  The postulates, theoretical support, and argumentative   framework substantiate our claims in which opinion is replaced with valid and   sound logical argumentation and supported with foundational theoretical and   descriptive justification from the medical literature.  While the tone   may be that of opinion, the descriptive and theoretical analysis, and   concluding call to action, is consistent with the enterprise of research   practices and collegial discussions. Thus, we respectfully believe this   manuscript should be categorized as an original article, and not merely a   letter to editor for which the gravity of this issue may go unnoticed.

We have added clarification of this issue within the   manuscript.

Please see Page 2, Lines 66-72.

Reviewer Comment

Authors’ Response

Page 3:

Line 85-98:  Suggest to   use the recently improved TAPS classification system and show stages based on   the recent improved classification system by Tollenaar et al.

We have   replaced our previous staging criteria example with an example of the   improved classification system by Tollenaar et al.

Please see   Page 3, Lines 102-111.

We chose   to leave a brief explanation regarding the evolution of the use of MoM values   to predict antenatal TAPS in an effort to assist readers who may not be aware   of the recent and preferential delta standard.

Line 99: other typical   “ultrasound” findings (suggestion to insert ultrasound)

Please see   Page 3, Line 117.

We also   deleted “antenatal” to limit repeated language in this portion of the paper.

Line 101: also starry sky   liver in the recipient can be added as additional ultrasound finding

Please see   Page 3, Line 119.

Line 116: suggestion to   insert: permanently life altering for “TAPS survivors and their” families.

Please see   Page 4, Line 134.

Page 6:

Line 185: suggestion to add:    recommend to use the improved antenatal classification system by   Tollenaar et al. Less TAPS cases will be missed and a delta is more   representative for the difference within the twins.

Please see   Page 7, Lines 209-211.

Reviewer Comment

Authors’ Response

When the authors report on the studies, which evaluated   the accuracy of MCA-PSV in predicting TAPS, the interval between the MCA   measurement and delivery should be mentioned for each study, as this interval   may influence the performance of this measurement.

For the four studies included in Table 1 we have added a column to   include information related to the interval between the timing of prenatal   MCA-PSV and delivery.

Please see modified Table 1 on Pages 5-6 (yellow highlights).

We have also added in the following sentence to the manuscript, “The   four studies in Table 1 included in their protocols a timely interval between   prenatal MCA-PSV and delivery (no greater than 1 week) increasing confidence   in the accuracy of the MCA-PSV measurements.”

Please see Page 4, Lines 164-166.

The authors should mention that value of MCA-PSV in   predicting polycythemia by itself is not as well established as its use for   prediction of fetal anemia. According to ref # 18, neonates with polycythemia   had similar MCA-PSV measurements compared to neonates with normal hemoglobin   level, and MCA-PSV>1MOM does not necessarily rule out fetal polycythemia.

Please see   Page 4, Lines 153-155.

In the section of MYTH 2 the authors should emphasize   that it seems that Delta MCA-PSV rather the actual MCA-PSV of each twin is   more accurate in prenatal detection of TAPS (ref 18 and ref 23).

We have   taken steps to clarify and emphasize this point in numerous parts of the   manuscript, including under MYTH 2.

Please   see, Page 3, Lines 98-99

Please see   Page 3, Lines 102-111.

Please see   Page 5, Lines 182-183.

In the section of MYTH 4 the authors should emphasize   that the different interventions for TAPS haven’t been shown to improve   perinatal outcome and that the flow chart presented is an expert opinion and   not evidence-based

Please see   Page 9, Line 299.

Please see   Page 9, Lines 309-310.

Additionally,   we have added a brief statement to this portion to help emphasize the premise   of the paper.

Please see   Page 9, Lines 303-305.

In the section of MYTH 4- in the paragraph discussing IUT   treatment, the authors should add that IUT does not only provide temporary   relief, but allows deferral of delivery and thus reduces the risk associated   with severe prematurity.

Please see   Page 9, Lines 293-294.

Reviewer Comment

Authors’ Response

The authors are making a case for argumentative and ethical   consideration for the study. However, the scientific question of whether   screening TAPS and implications of false positive or false negatives are not   explored.

The   issue of how Doppler MCA-PSV false positives and/or false negatives influence   TAPS screening is explored in MYTH 2 and MYTH 5.

We   address this issue in a few different ways:

1)    By   discussing the specific levels of sensitivity (used to assess false   positives) and specificity (used to assess false negatives) as outlined in   the relevant literature.

These findings can be found in Table 1 (pages 5-6) as well as on   pages 4-5, Lines 169-181.

We have added additional clarification on Page 7 to include the   specificity/false negative findings. Please see Page 7, Line 207.

Overall   findings confirm that MCA-PSV Doppler sensitivity and specificity levels are   high and acceptable. 

2)    By reviewing   the literature to suggest ways in which MCA-PSV Doppler screening technique can   be adjusted to maximize accurate screening results.

Please see Page 4, Lines 144-151.

Additionally, we include discussion regarding the value of   adopting of delta MoM values to catch more TAPS cases and the use of serial   MCA-PSV screening to reduce false negatives.

Please see Page 7, Lines 196-212.

This is reiterated on Page 10, Lines 316-328.

3)    By   discussing the ability for MCA-PSV Doppler screening results to prompt   interventions that may result in premature birth.

Please see MYTH 8 on Page 11, Lines 368-382.

4)    By   discussing clinicians’ prevailing ethical obligation and rights of the   patient to be offered the option for TAPS screening regardless of the (low   and acceptable) possibility of false positives and/or false negatives.

Please see   Page 12, Lines 419-427.

Finally,   we would like to highlight that the discussion of the implications of faulty   MCA-PSV Doppler readings is an important but minor portion of the overall   paper. That is, there are many prevailing myths working to withhold routine   TAPS screening from women in the United Sates and issues surrounding   potential false positives and/or false negatives represents a small portion   of these myths. Therefore, false positives and/or false negatives are not the   main focus of the paper, and are thus discussed in proportion to the   influence they are having on the withholding of routine TAPS screening.

Complementary   to this, the entire paper is founded on the argument that despite inherent   flaws in testing or established treatment protocol (which throughout the   paper we admit exist), the only person who can make the decision to accept or   reject the risks and benefits of routine TAPS screening is the patient   herself.