Consensus update on twin‐twin transfusion syndrome staging: An international Delphi study

Abstract

Introduction

Twin‐twin transfusion syndrome (TTTS) affects approximately 15% of monochorionic pregnancies and results in poor outcomes without treatment. The Quintero staging system has been used to characterize the severity of the syndrome and has been widely adopted due to its simplicity. However, it has been interpreted to indicate a chronological and synchronous evolution of TTTS disease that has been increasingly called into question. We sought to update the current staging system for TTTS to reflect current understanding of the underlying pathophysiology and to optimize guidance for clinical decision making and future research.

Methods

A four‐round Delphi procedure was conducted among an international panel of experts on TTTS to obtain consensus on an updated staging system. A core group of experts chosen based on their scholarship, international reputation, and medical specialty provided input on fact statements for the first two rounds. A larger group of experts was included in Rounds 3 and 4 and participation in round 4 was not contingent on participation in round 3. Consensus was defined as agreement of ≥ 70%.

Results

A total of 462 experts from three continents were approached during the four rounds. The core group consisted of 16 experts, of which 15 (93.8%) completed all rounds. An additional 79 experts participated in round 3 (total of 94, response rate 20.3%) and an additional 18 experts participated in round 4 (total of 112, response rate 24.2%).

Four areas of proposed changes were identified: (1) identification of a subgroup of monochorionic pregnancies at increased risk for progression to TTTS (“pre‐TTTS”), (2) differentiation between donor and recipient disease for stages III and IV, (3) modifications to critically abnormal fetal cardiovascular findings defining stage III TTTS, and (4) recognition that TTTS with evidence of severe cardiac compromise can present without a fluid discordance satisfying classic criteria for stage I (“atypical TTTS”).

Conclusion

The updated consensus‐based staging system for TTTS aims to improve clinical care by allowing earlier and more specific identification of disease, standardizing follow‐up, and facilitating more robust research into TTTS's natural history, management, and outcomes. Prospective validation is warranted to assess its clinical utility.

1. INTRODUCTION

Twin‐twin transfusion syndrome (TTTS) affects approximately 15% of monochorionic pregnancies [1] and results in poor outcomes without treatment [2, 3]. TTTS is a multi‐system disease resulting from volume imbalance and hormonal factors traversing placental vascular anastomoses, contributing to profound hemodynamic shifts for both donor and recipient [4, 5]. Fetoscopic laser coagulation (FLC) of communicating placental vessels interrupts the volume and substance exchange between co‐twins and has significantly improved the odds of survival [6, 7, 8].

The Quintero staging system characterizes TTTS severity [9] and has been widely adopted. However, this staging system has been interpreted to indicate a sequential and synchronous progression of the disorder between donor and recipient that no longer reflects our current understanding of TTTS pathophysiology [10]. It has been criticized due to its lack of differentiation between donor and recipient disease—two completely different conditions which do not typically evolve synchronously [11]. Recipient TTTS is characterized by volume overload and congestive (predominantly right) heart failure [5] while donor disease can overlap with selective fetal growth restriction (sFGR) and is associated with hypovolemia and increased angiotensin production [12]. Thus, TTTS presents with renal and cardiovascular manifestations, which do not predictably progress at the same rate in both twins [13].

The Quintero definition of stage III: absent or reversed end‐diastolic velocity (a/r EDV) in the umbilical artery (UA), reversed a‐wave in the ductus venosus (DV), or pulsations in the umbilical vein (UV) misses all but the most extreme forms of cardiovascular compromise in the recipient. Marked cardiac dysfunction in the recipient is often apparent prior to a reversed a‐wave in the DV or pulsations in the UV [14].

In addition, TTTS may present with advanced recipient disease (stage III or IV) in the absence of diagnostic fluid abnormalities. This may create a false sense of security about the absence of TTTS and thus these “atypical” cases may be overlooked unless venous Dopplers or cardiac assessment is performed [15, 16].

Stages II–IV are typically managed by urgent referral to a fetal center for FLC. Treatment for stage I disease, which progresses in up to 60% of cases [17], depends on maternal symptoms, cervical length, proximity to a fetal center, and additional clinical findings such as cardiac dysfunction in the recipient. However, there is uncertainty about how to manage pregnancies that present with a fluid discordance not meeting criteria for stage I, though closer follow‐up has been proposed [18].

Efforts to modify the staging system for recipient disease such as the CHOP cardiovascular score [19], or the Cincinnati scoring system [20] may predict outcomes for recipients [21]. Despite their merits, neither has been widely implemented as both require advanced cardiac assessment, which may be unavailable in the urgent timeline typically required for TTTS evaluation and management.

We sought to update the Quintero staging system for TTTS to reflect current understanding of the underlying pathophysiology and varied presentations. The goal is to allow for better guidance on clinical decision‐making and future research. We also wanted to retain the element of simplicity, so that staging can be carried out reliably outside of specialized fetal centers.

2. METHODS

We used the Delphi method [22] with an international panel of experts to maximize the chances of adoption of an updated staging system for TTTS in accordance with the Guidance on Conducting and Reporting Delphi Studies (CREDES) [23]. The Delphi method is an iterative survey method to collect expert opinions and is increasingly used to develop clinical guidelines [22]. Benefits of the Delphi method include a feedback loop to refine questions, anonymity, and the potential to include experts from different geographic locations [24].

Two groups of experts participated in our study (see Figure 1). A core group of 16 international experts was selected based on their history of scholarship, international reputation, and representation of medical specialties involved in the screening and treatment of TTTS to develop and refine the questions over two rounds [22]. The group included global experts in maternal fetal medicine, pediatric surgery, radiology, and cardiology, and leaders in the Society for Maternal Fetal Medicine (SMFM), the Fetal Heart Society, the North American Fetal Therapy Network (NAFTNet), and the International Fetal Medicine and Surgery Society (IFMSS) (see Table 1). Participants who declined the invitation recommended an alternate senior physician from their department to participate.

FIGURE 1.

Outline of the Delphi study process and participants.

TABLE 1.

Details on 16 experts on TTTS participating in the Delphi study.

Characteristic	n
Region of Practice
USA (East)	3
USA (Central)	3
USA (West)	4
Canada	1
Europe	3
Asia	2
Years of experience in the diagnosis and treatment of TTTS
5–10 years	1
11–15 years	4
16–20 years	1
21–25 years	3
> 25 years	7
Estimated number of twin pregnancies evaluated annually at institution
< 50	0
50–100	3
100–200	6
200–300	2
> 300	5
Estimated number of fetoscopic laser photocoagulation for TTTS annually
< 10	1
10–30	3
30–50	5
50–70	4
> 70	3
Specialty
Maternal fetal medicine	13
Pediatric cardiology	1
Radiology	1
Pediatric surgery	1

Abbreviation: TTTS, twin‐twin transfusion syndrome.

To explore the broader acceptability of an updated TTTS staging system, a larger group of experts consisting of IFMSS annual meeting attendees and NAFTNet members was invited to vote on items identified by the core group in Rounds 3 and 4 (Figure 1). Participation in round 4 was not contingent on participation in round 3 [22]. Questionnaires were designed using the research electronic data capture (REDCap) platform to collect anonymous responses and comments. Exempt approval was obtained from the Seattle Children's Hospital IRB. Participants received an invitation by email and were informed that answering the questions was considered consent to participate in the study. Non‐responders received an email reminder at 7 and 14 days.

2.1. Delphi rounds

During a brainstorming session, core group experts were invited to share their challenges and critiques of the current system as well as their proposed changes. Consensus statements about stage V TTTS were not explored since adjustment in staging is not anticipated to impact management. We also solicited input on follow‐up recommendations for pregnancies demonstrating fluid discordance not meeting criteria for TTTS. This session was the basis for the questions posed in round 1 of the Delphi procedure.

2.1.1. Round 1

Based on the brainstorming session, fact phrases were presented to the panel. Participants were asked to rate their agreement with the fact phrases based on a 5‐point Likert scale (5 = strongly agree, 4 = agree, 3 = neutral, 2 = disagree, 1 = strongly disagree), with an option to suggest additional considerations. Additional questions related to the experts’ experience of TTTS.

2.1.2. Round 2

In the second round, data from the first round were shared in aggregate form. Questions were edited for clarity, and participants had the option to revise their responses. Modified fact statements from the first round were presented back, and participants were asked to rate these on a 5‐point Likert scale, with the option to provide additional comments. One question involved additional markers for stage III recipient disease. Participants were also presented with seven scenarios on frequency of follow‐up (2 weeks, 1 week, or 2x/week). Items with a median score of 5 without suggestions for modifications were considered consensus and were not included in subsequent rounds. Phrases with a median score of 3 or less were deemed non‐consensus and eliminated from subsequent rounds. Phrases with a median score of 4 were modified based on the comments and included in round 3.

2.1.3. Rounds 3 and 4

Input from a larger group of experts actively involved in screening for and treating TTTS was sought to gauge the acceptability of an updated TTTS staging system. Experts were asked to vote (“agree” or “disagree”) on statements and to provide comments. Consensus was defined as agreement among 70% or more of the experts. Items with 65%–69% agreement and comments were modified and resubmitted in the final round. In the fourth round, a single item was presented for consideration to the larger expert group. Consensus was defined as 70% or more agreement.

3. RESULTS

All 16 core experts who participated in the brainstorming session participated in the first round of the Delphi procedure and 15/16 (93.8%) responded in rounds 2–4. The core group represented three continents and primarily consisted of maternal fetal medicine specialists (13/16, 81%), with additional representation by pediatric cardiology, radiology, and pediatric surgery. Experts with > 15 years of experience managing TTTS made up 69% of the core group, and 75% performed > 30 FLC procedures yearly. Details regarding demographics, specialty, and level of expertise are shown in Table 1. For rounds 3 and 4, IFMSS annual meeting attendees (n = 156) and NAFTNet members (n = 306) were invited to participate. These included members of the core group. As there was an overlap between these groups, experts were asked to fill out the survey only once per round.

In round 1, 28 fact statements were presented to the core expert group. For a summary of questions and answers, see Section S1. Based on the responses, 20 modified fact statements were presented in round 2. Three received a median score of 5 and were considered consensus, and three received a median score of 3 or less and were not included in subsequent rounds. Six fact statements with a median score of 4 were modified based on comments and included in round 3. Two potential markers for stage III that reached > 70% of votes were also included in round 3. For a summary of round 2, see Section S2.

For round 3, 94/462 experts responded, for a response rate of 20.3%. Sixteen fact phrases received an agreement of 70% or more and were considered consensus. Four fact statements with agreement of < 65% were removed from the survey. Two fact statements with agreement of 65%–69% and suggestions and comments were modified and resubmitted as a single fact statement in the final round (see Section S3). Round 4 included one single item and 112/462 experts from the same cohort as round 3 responded for a response rate of 24.2%. The single item reached consensus agreement (see Section S3).

Table 2 lists all consensus statements. A revised Delphi staging system for TTTS based on these consensus statements is proposed in Table 3. Table 4 highlights the differences between the Quintero and the proposed Delphi staging systems. There was consensus that monochorionic twins’ routine surveillance should include UA and middle cerebral artery (MCA) Dopplers. There was also consensus that a subset of pregnancies with fluid discordance not meeting criteria are at risk of progression and should be followed more closely than the standard 2‐week interval. Consensus was achieved on naming this presentation “pre‐TTTS”. There was also consensus that a shorter screening interval may be indicated by sFGR and the development of maternal symptoms. There was no consensus regarding changing the fluid criteria of stage I to Eurofoetus criteria—MVPs of ≥ 8 cm/ ≤ 2 cm prior to 20 weeks and ≥ 10 cm/ ≤ 2 cm after 20 weeks—(59% agreement). While retaining the Quitero stage I fluid criteria cutoffs, we chose to use inclusive cutoffs (≥ and ≤) following the lead of the Eurofoetus trial [7] and the common definition of polyhydramnios as an MVP of at least 8 cm.

TABLE 2.

Fact phrases regarding the screening of monochorionic multiples and staging of TTTS for which met predefined consensus criteria, as voted on by experts in the third and fourth rounds of the Delphi procedure.

Fact phrase	Votes (% in favor)
Monochorionic multiples surveillance should include umbilical artery Dopplers.	76
Monochorionic multiples surveillance should include MCA Dopplers.	81
While MCA Dopplers are not part of the definition of TTTS, they should be part of every TTTS evaluation due to overlap between TAPS and TTTS.	100
Follow‐up in one week or less is indicated for a fluid discordance (isolated polyhydramnios, isolated oligohydramnios or a fluid discordance within 1 cm of the cutoff proposed by Quintero (i.e. 7 cm/3 cm).	93
A fluid discordance not otherwise explained by other causes can be called “Pre‐TTTS,” (without implication that all of these cases progress to TTTS).	71
A follow‐up interval of one week or less is indicated for abnormal Dopplers.	97
A follow‐up interval of one week or less is indicated for maternal symptoms.	71
A follow‐up interval of one week or less is indicated for early onset sFGR.	78
Stage I TTTS fluid criteria should remain the same at all gestational ages.	82
Stage II TTTS should remain non‐visualized bladder on the donor.	94
MCA discordance should not be part of TTTS staging criteria.	94
Stage III TTTS should be further defined as stage III donor, stage III recipient, or stage III donor + recipient.	83
Persistent absent or reversed EDV in the umbilical artery (as opposed to intermittent or cyclical) should be included in the definition of stage III TTTS.	78
Absent a‐wave of the ductus venosus should be included in the definition of stage III (in addition to reversed a‐wave)	88
Severe tricuspid regurgitation as a marker of cardiac dysfunction should be included in the definition of stage III.	84
Stage III recipient disease (polyhydramnios, abnormal DV or UV, TR) can occur in the absence of oligohydramnios (MVP < 2 cm) in the donor.	90
Stage IV should remain hydrops.	100

Abbreviations: DV, ductus venosus; EDV, end‐diastolic velocity; MCA, middle cerebral artery; MVP, maximal vertical pocket; TR, tricuspid regurgitation; TTTS, twin‐twin transfusion syndrome; UV, umbilical vein.

TABLE 3.

Delphi staging system of TTTS (modification to Quintero staging [9] in bold font).

	Amniotic fluid	Bladder visible (donor)	Dopplers (UA, UV, DV, TR)	Hydrops
Pre‐TTTS	Discordant a	Yes	All normal	No
TTTS
Stage I	MVP ≥ 8 cm MVP ≤ 2 cm	Yes	All normal	No
Stage II	MVP ≥ 8 cm MVP ≤ 2 cm	No	All normal	No
Stage III Recipient, IIIR	MVP ≥ 8 cm MVP ≤ 2 cm b	Yes or no	Any of the following: absent or reversed a‐wave in the recipient DV severe recipient TR pulsatile recipient UV a/r EDV in recipient UA (rare)	No
Stage III Donor, IIID	MVP ≥ 8 cm MVP ≤ 2 cm	Yes or no	Any of the following: a/r EDV in donor UA absent or reversed a‐wave in the donor DV pulsatile donor UV severe donor TR (rare)	No
Stage III Donor +Recipient, IIID+R	MVP ≥ 8 cm MVP ≤ 2 cm b	Yes or no	Meets criteria for stage III donor and stage III recipient	No
Stage IV Recipient Donor	MVP ≥ 8 cm MVP ≤ 2 cm b	Yes or no	Same as for stage III	Yes

Abbreviations: a/r EDV,  absent or reversed end‐diastolic velocity; DV,  ductus venosus; MVP,  maximal vertical pocket; TR,  tricuspid regurgitation; TTTS, twin‐twin transfusion syndrome; UA , umbilical artery; UV,  umbilical vein.

^a Polyhydramnios (MVP ≥ 8), or oligohydramnios (MVP ≤ 2), or discordant fluid (MVP ≥ 7 and MVP ≤ 3). Pre‐TTTS does not imply progression to TTTS. If possible, perform Dopplers used for staging and follow‐up at a closer interval than 2 weeks (ideally ≤ 1 week).

^b If polyhydramnios and abnormal Dopplers in the recipient are present without oligohydramnios ≤ 2 cm on donor, describe as “atypical stage III‐IV recipient” or “isolated recipient disease.”

TABLE 4.

Comparison of Quintero staging for TTTS and Delphi staging system for TTTS.

Stage	Quintero	Delphi
Pre‐TTTS	NA	Discordant fluid MVP ≥ 8, or MVP ≤ 2, or MVP ≥ 7 and MVP ≤ 3
Stage I	MVP > 8 cm and MVP < 2 cm donor bladder visible	MVP ≥ 8 cm and MVP ≤ 2 cm donor bladder visible
Stage II	MVP > 8 cm and MVP < 2 cm donor bladder not visible	MVP ≥ 8 cm and MVP ≤ 2 cm donor bladder not visible
Stage III	MVP > 8 cm and MVP < 2 cm Absent bladder ± reversed a‐wave in the DV a/r EDV in the UA pulsative UV	MVP ≥ 8 cm and MVP ≤ 2 cm Absent bladder ± absent or reversed a‐wave in the DV a/r EDV in the UA pulsative UV severe TR add designation “donor,” “recipient,” or “donor and recipient”
“Atypical stage III” or “isolated recipient disease”	NA	MVP ≥ 8 cm and MVP > 2 cm Absent bladder ± absent or reversed a‐wave in the DV a/r EDV in the UA pulsative UV severe TR
Stage IV	Meets criteria for stage III plus hydrops	Meets criteria for stage III plus hydrops add designation “donor,” “recipient,” or “donor and recipient”
Stage V	Meets criteria for stage IV plus demise	NA

Abbreviations: DV, ductus venosus; MVP, maximal vertical pocket; TR, tricuspid regurgitation; TTTS, twin‐twin transfusion syndrome; UA, umbilical artery; UV, umbilical vein.

There was consensus on adding a designation for stages III and IV based on which fetus is affected (donor, recipient, or both) and adding absent a‐wave in the DV and severe tricuspid regurgitation (TR) to the findings defining stage III. For Dopplers of the UA, there was consensus to specify “persistent” (rather than cyclical or intermittent) a/r EDV. There was consensus that findings consistent with stage III recipient disease (polyhydramnios, abnormal DV or UV, TR) can occur in the absence of oligohydramnios (MVP ≤ 2 cm) in the donor/co‐twin, but there was no consensus on what to call this presentation. The majority of experts (57 %) stated that they would agree to call this “atypical” TTTS, 23.4% would call it “isolated recipient disease,” and 9.6% stated that it met their criteria for TTTS while 9.6% said they did not believe this presentation represented TTTS.

4. DISCUSSION

This Delphi study proposes four key updates to the Quintero staging system based on international expert consensus. These include: (1) identification of a subgroup of monochorionic pregnancies at increased risk for progression to TTTS (“pre‐TTTS”), (2) differentiation between donor and recipient disease for stages III and IV, (3) modifications to critically abnormal findings defining stage III TTTS to include absent a‐wave in the DV and severe TR, and (4) recognition that evidence of severe cardiac compromise can present without a fluid discordance satisfying criteria for stage I TTTS.

4.1. Preclinical TTTS (“Pre‐TTTS”)

We propose the designation of “pre‐TTTS” for monochorionic pregnancies with a fluid discordance not meeting stage I TTTS fluid criteria to highlight the need for closer follow‐up. Consensus criteria for this were isolated polyhydramnios, isolated oligohydramnios, or a fluid discordance within 1 cm of stage I criteria (i.e., ≥ 7 cm and ≤ 3 cm). A recent study [25] demonstrated that pregnancies with fluid abnormalities that did not meet criteria for TTTS had a significantly elevated risk of development of TTTS (41%), twin anemia polycythemia sequence (TAPS) (8%), new onset sFGR (11%), need for laser (36%), fetal demise (11%), and maternal admission for fetal surveillance (15%). Van Mieghem et al. noted that the risk of progression to TTTS for twins with amniotic fluid discordance of 3.1 cm or more was higher (86%) before 20 weeks and suggested a surveillance interval of 2–3 days for this gestational age [26]. Yamamoto et al. [27] proposed a fluid discordance cutoff of 4 cm as a predictor for progression which aligns with our criteria. Progression often occurs in the first 2 [26] to 4 weeks [25] after initial diagnosis, mandating increased vigilance during this time. Follow‐up should be at least weekly until findings normalize or remain stable over 4 weeks [25] and should ideally include Doppler measurements that define stage III to detect atypical TTTS [28, 29]. In the absence of progression or atypical TTTS, expectant management under heightened surveillance is appropriate.

4.2. Differentiation between donor and recipient disease for stages III and IV

The staging system has been erroneously interpreted as reflecting a natural progression of TTTS with sequential stages affecting donor and recipient with equal severity [11]. In reality, donor and recipient disease are distinctly different conditions and often present with discordant severity. Risk factors for demise post‐FLC differ between donor and recipient [30], underscoring the need to differentiate between donor and recipient for stages III and IV disease.

TTTS stages I and II reflect volume status and the renal manifestations of TTTS, while stages III and IV are based on cardiovascular manifestations (Figure 2). The severity of renal manifestations (i.e., the degree of oligohydramnios and polyhydramnios) does not reliably correlate with cardiac manifestations [15, 16], suggesting a benefit to assess cardiovascular function for all monochorionic twins with fluid discordance [29].

FIGURE 2.

In the donor, the net transfer of blood to the recipient triggers the activation of the renin angiotensin aldosterone system (RAAS) as a compensatory mechanism, leading to vasoconstriction, oliguria, and abnormal umbilical artery (UA) Dopplers. In contrast, recipient disease is caused by a combination of hypervolemia leading to increased preload and increased afterload from exposure to the RAAS environment of the donor. These factors contribute to polyhydramnios and impaired cardiac function. DV, ductus venosus; GFR, glomerular filtration rate; TR, tricuspid regurgitation; UV, umbilical vein.

In the donor, the net transfer of blood to the recipient triggers the activation of the renin angiotensin aldosterone system (RAAS) as a compensatory mechanism, leading to vasoconstriction (Figure 2) [31, 32]. This may exacerbate features of sFGR and abnormal UA Dopplers [33]. There is an overlap of stage III donor with sFGR [11], which may cause abnormal UA flow patterns in itself. The heart function of the donor is usually normal, and any diastolic dysfunction is thought to be due to the effects of FGR [34]. Donors with abnormal Dopplers are at increased risk of perioperative demise [35]. A distinction between stage III donor or recipient has the potential to facilitate research into which fetuses might benefit from experimental surgical or medical treatment approaches [35, 36] when adjusting outcomes based on stage. Cyclical abnormalities in the UA are more likely a reflection of artery‐to‐artery anastomoses than severe TTTS and were thus excluded from the definition of stage III.

In contrast, stage III recipient disease is caused by hypervolemia, leading to increased preload and increased afterload from exposure to the RAAS environment of the donor (Figure 2) [37, 38]. These factors contribute to diastolic dysfunction, decreased cardiac contractility, systolic dysfunction, and atrioventricular valve regurgitation, which ultimately can result in cardiac failure [39]. Up to 50% of recipients in stages I and II already show marked cardiac dysfunction [14].

The distinction between donor and recipient disease draws attention to the different pathophysiological pathways and may facilitate the interpretation of sonographic findings and comparison of outcomes.

4.3. Modifications to critically abnormal findings defining stage III TTTS

Stage III has been defined as reversed a‐wave in the DV, a/r EDV in the UA, or pulsations in the UV in either fetus [9]. We achieved consensus on adding absent a‐wave in the DV and severe TR to the critical findings that define stage III. Many centers are already including “absent or reversed a‐wave of the DV” in their definition of stage III, so we are suggesting formalizing this practice. The addition of severe TR serves as a measure of cardiac dysfunction that may precede abnormalities in the DV. The Quintero staging system was proposed in 1999 before the prevalence and the spectrum of cardiovascular disturbances had been fully appreciated [15]. A comprehensive body of research in the intervening time has demonstrated that subtle cardiac dysfunction is present early in the disease [29, 40, 41] and increases as the disease progresses [42].

Expectant management is often suggested for otherwise asymptomatic stage I [43], however, waiting until venous pulsations or reversed a‐wave in the DV are present in the recipient may incur an increased risk of myocardial damage, ventricular hypertrophy, and acquired critical pulmonary stenosis [44]. In addition, a subset of stage I will demonstrate rapidly progressive cardiovascular impairment [13]. Other authors have called for assessing cardiovascular manifestations rather than depending on the renal manifestation of bladder filling versus non‐filling as a more robust basis on which to offer FLC earlier than is currently the standard [40]. While some investigational cardiovascular parameters such as DV time intervals hold promise to predict worsening of TTTS earlier [41, 45, 46], these are only available on fetal echocardiograms done at specialized fetal centers.

The addition of absent a‐wave of the DV and severe TR maintains the balance of increasing the sensitivity of detecting cardiac dysfunction with the feasibility of performing staging of TTTS at referring sites rather than fetal therapy centers. Severe TR can easily be identified by color and pulsed Doppler. While there is no one universally accepted definition of what constitutes “severe” versus “moderate” tricuspid regurgitation [47], we suggest that the standard used at each institution be followed, with input from pediatric cardiology if imaging is equivocal. Components defining severe TR may include holosystolic regurgitation, the color jet reaching the back wall of the atrium, width of the color jet > 7 mm, and velocity of > 60 cm/s.

4.4. Recognition that TTTS with evidence of recipient cardiac compromise can present without a fluid discordance satisfying criteria for stage I (“atypical TTTS”)

As suggested by other authors [15, 48], there was consensus that a subset of monochorionic twin pregnancies exhibits advanced recipient TTTS without donor anuria and does not meet criteria for oligohydramnios. Alternatively, severe recipient cardiac failure may decrease renal perfusion and result in a lack of polyhydramnios. Although the incidence, characteristics, and outcomes of this subset are largely unexplored, one retrospective series identified the prevalence of this presentation (characterized by stages III and IV recipient disease) at 7.2% [16]. Abnormal Dopplers and hydrops resolved after FLC, with survival on a par with typical TTTS, suggesting an analogous cause. However, current recommendations do not suggest cardiovascular evaluation in the absence of stage I TTTS and do not provide guidance on the treatment of these cases. This may inhibit fetal therapy specialists from offering invasive therapy in these atypical cases [15] and impedes research on the incidence, characteristics, and outcomes. Including these cases as a distinct entity in a staging system of TTTS will facilitate the differentiation from non‐TTTS pathology, enhance identification, and allow comparison of results with FLC to investigate the preferred treatment. A total of 82% of respondents agreed that it should be differentiated from TTTS. A majority (57%) agreed to call this “atypical TTTS,” so we suggest using this nomenclature.

A strength of this study is that it reflects expert insight into advances in our understanding of the pathophysiology of TTTS. We strived to retain the simplicity of Quintero staging to allow for implementation outside of specialized fetal therapy centers. The strength of the recommendations of a Delphi procedure depends on the participants. We selected experts with a wealth of clinical experience and included diverse specialties that are involved in evaluating and treating TTTS across a wide geographic distribution. The demographics of the core expert panel reflect a highly experienced group with a median of 21–25 years’ experience in performing fetoscopy with a median of 50 procedures annually at their institution. We invited a broad range of experts to vote on items that had been formulated with the core expert panel to reduce bias and gauge widespread acceptability. All participants’ votes were equally weighted. We used predefined parameters for the definition of consensus. When there were ambiguous interpretations of questions, subsequent rounds were used to clarify the answers and allowed participants to adjust their answer informed by feedback.

A limitation of a Delphi procedure is the potential for bias by the participants. To mitigate peer pressure, the participants received feedback regarding others’ responses only in aggregate form. To encourage participants to openly express their opinions, we allowed free text comments for each group of questions.

In conclusion, our study proposes an updated, consensus‐based staging system for TTTS. We submit the revised definition that may improve the identification of preclinical and atypical cases, guide the intensity of follow‐up, and facilitate timely referral for FLC when appropriate. The proposed staging system also supports collaborative research into the natural history, progression, treatment strategies, and outcomes of these complicated pregnancies. By allowing clearer differentiation of disease severity and patterns, these changes may enhance the comparability of clinical data and support the development of customized treatment approaches.

Prospective validation of this consensus‐based staging system is warranted to assess its clinical utility in improving risk stratification and guiding management of TTTS. While not part of the proposed staging system, the interaction with sFGR and TAPS also merits further investigation.

CONFLICT OF INTEREST STATEMENT

Dr. Paek and Dr. Walker have served as expert witnesses regarding TTTS and have a financial interest in an educational patient application, eDoula. Dr. Običan has served as an expert witness in her capacity as a reproductive toxicologist. Dr. Johnson and Dr. Papanna have served as expert witnesses. Dr. Lewi is supported by a grant from the Research Foundation Flanders.

FUNDING INFORMATION

The authors received no specific funding for this work.

Supporting information

Supporting Information