Ultrasound Obstet Gynecol 2016; 47: 667–671 Published online 3 May 2016 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.15852

Editorial Prenatal counseling for neurodevelopmental delay in congenital heart disease: results of a worldwide survey of experts’ attitudes advise caution D. PALADINI*†, Z. ALFIREVIC‡, J. S. CARVALHO§, A. KHALIL¶, G. MALINGER**, J. M. MARTINEZ††, J. RYCHIK‡‡ and H. GARDINER§§ †Fetal Medicine and Surgery Unit– Istituto G.Gaslini, Genoa, Italy; ‡Department of Women’s and Children’s Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK; §Fetal Medicine Unit, St George’s University of London; and Brompton Centre for Fetal Cardiology, Royal Brompton Hospital, London, UK; ¶Fetal Medicine Unit, Department of Obstetrics and Gynaecology, St George’s Hospital, London, UK; **Ob-Gyn Ultrasound Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; ††Fetal Medicine, Barcelona Center for Maternal Fetal and Neonatal Medicine, Hospital Cl´ınic and Sant Joan de D´eu, University of Barcelona, Barcelona, Spain; ‡‡Fetal Heart Program, Children’s Hospital of Philadelphia, PA, USA; §§The Fetal Center, University of Texas Health Science Center at Houston, Houston, TX, USA *Correspondence. (e-mail: [email protected])

balloon atrial septostomy and after surgery in neonates with TGA, new lesions have been described, despite strategies to optimize perioperative care11 – 13 . Studies have reported that periventricular leukomalacia is associated with low baseline CBF and an MRI-derived maturation score demonstrated brain immaturity in the CHD cohort8 . The weight of evidence from imaging and clinical studies documenting brain lesions and likely risk of NDD in the fetus with CHD has raised concern among health professionals involved in prenatal counseling14 – 17 . However, the correlation of MRI findings with neuropathology remains inconclusive in most studies18 – 23 and the clinical implications are uncertain and discordant with some pediatric cardiologists’ experience. There are concerns that discussing adverse neurodevelopmental outcomes may lead couples to terminate pregnancy for isolated CHD associated with low mortality and long-term morbidity. These uncertainties led us to prepare a web-based survey to circulate among CHD referral units worldwide, to gather information on healthcare professionals’ practice, their understanding of the evidence base for NDD in CHD and the way in which they convey this information during prenatal counseling.

The questionnaire (Appendix S1)

Introduction An association between congenital heart disease (CHD) and neurodevelopmental delay (NDD) has long been recognized, but remains poorly understood. The Boston Circulatory Arrest randomized controlled trial showed no difference in NDD following different surgical bypass techniques for transposition of the great arteries (TGA)1 . However, assessment at 16 years of age described mild NDD in half of these2 , and up to 30% of CHD surgery survivors are reported to require special education and rehabilitation services3,4 . Current research on CHD attempts to determine the precise nature and timing of brain damage. There is a long period of potential vulnerability during white-matter development in the fetal brain5 and alteration of blood flow and metabolic substrates due to CHD may contribute to the risk of damage. Genetic contributors, such as apolipoprotein E, in combination with other risk factors, such as low birth weight and genetic syndromes, are associated with NDD6 . Lowered fetal cerebral resistance7 and reduced cerebral blood flow (CBF) have been reported in TGA and hypoplastic left heart syndrome (HLHS)8 , with an increased rate of microcephaly in the latter9,10 . Magnetic resonance imaging (MRI) has shown lesions suggesting brain injury before cardiac surgery. Following

Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

A participant database of e-mail addresses was created from national and international societies of fetal medicine experts and pediatric cardiologists involved in fetal cardiology. A healthcare professional was included in the mailing list only if they met all of the following criteria: 1) leading expert with publications in the field of fetal and neonatal CHD; 2) working in referral centers for fetal and neonatal CHD; and 3) actively carrying out prenatal counseling for CHD. Exclusion criteria were: 1) working in a private-only facility; and 2) working in referral centers but not involved in prenatal counseling. In this way, a list of 297 fetal medicine and pediatric cardiology experts was generated. The specialists identified were asked to participate in a survey on their attitudes towards prenatal counseling for CHD. A web-based questionnaire (Appendix S1) was sent by email between May and July 2015, with two reminders to non-responders sent at 3-month intervals. Geographically, four continents were included: North America, South America, Europe (including Israel) and Asia. The survey consisted of three components: the first identified the specialty background of the expert and the case load of the center; the second aimed to gauge the degree to which the individual participant agreed with the conclusions of the literature regarding the risk of NDD in fetuses/neonates with CHD, whether this was discussed in routine counseling for CHD and, if so, how the information was delivered; the third inquired about local routine protocols for

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Paladini et al.

668 Table 1 Distribution of the 150 replies received to questionnaires sent to fetal medicine experts and pediatric cardiologists involved in fetal cardiology on their attitude towards prenatal counseling for congenital heart disease, according to respondent’s country

USA (United States of America) France China Italy UK (United Kingdom) Spain Israel India The Netherlands Brazil Germany Martinique Belgium Canada Indonesia Argentina Austria Denmark Poland Sweden Taiwan Afghanistan Total

35 30

% (n) 22.8 (34) 14.8 (22) 12.1 (18) 10.1 (15) 8.7 (13) 6.0 (9) 4.0 (6) 4.0 (6) 2.7 (4) 2.7 (4) 2.0 (3) 2.0 (3) 1.3 (2) 1.3 (2) 1.3 (2) 0.7 (1) 0.7 (1) 0.7 (1) 0.7 (1) 0.7 (1) 0.7 (1) 0.7 (1) 150

Number of replies

Country

Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

25

23 20

20 15

11

10

10

10

7

5 0

5 3

2

4 2

1

0–10

No TOP

11–30

>50

31–50

TOP rate (%)

Figure 1 Rate of termination of pregnancy (TOP) in cases of isolated congenital heart disease, according to geographical location of the institutions of respondents to questionnaire on experts’ attitudes towards prenatal counseling. , North America; , South America; , Europe; , Asia.

80

To the 297 questionnaires originally sent out, 150 (50.5%) replies were received, from 123 referral centers in 22 countries.

71

70 Number of replies

MRI and clinical assessment of brain development and neurodevelopmental function, respectively. The questionnaire gathered qualitative data, and free-text fields accompanied most questions, to enable entry of additional information and comments from the participants. To the 297 emails sent to expert professionals, 150 (50%) replies were received, from 123 referral centers in 22 countries (the majority being from USA, France, China, Italy and UK; Table 1). Healthcare professionals who replied included 86 (57.3%) fetal/pediatric cardiologists, 51 (34.0%) fetal medicine experts, three (2.0%) radiologists and 10 (6.7%) from other specialties, such as neonatology and neurology. Eighty-five (56.7%) of the respondents saw more than 70 fetuses with CHD per year, 21 (14%) saw 51–70 cases, 25 (16.7%) saw 21–50 cases and 19 (12.7%) saw 20 or fewer cases per year. The rate of termination of pregnancy (TOP) in cases of isolated CHD was reported to be 10% or lower by 51 (37.0%) of the 138 respondents who replied to this question, 11–30% by 55 (39.9%) respondents, 31–50% by 15 (10.9%) respondents and above 50% by 12 (8.7%) respondents. There was a significant geographical difference in TOP rates (P < 0.001; Figure 1). Most physicians responded that prenatal counseling was carried out by a multidisciplinary team (102/143; 71.3%), while 41 (28.7%) stated that this was usually done by a single counselor. Twenty-four physicians said that the personnel varied depending on circumstances,

40

40

60 50 38

40 30 20 10 0

12 3

2

11

No

8

4

1

Partially

Yes

Reply

Figure 2 Breakdown of replies to the question, ‘Are you aware of the increasing amount of literature on the topic of possible brain lesions/neurodevelopmental delay associated with congenital heart disease from fetal life?’, according to specialty of respondent. , pediatric cardiologist; , fetal medicine expert; , other, e.g. radiologist, neonatologist.

including the complexity of the case. Professionals involved in the multidisciplinary prenatal counseling sessions were usually fetal medicine experts (86; 84.3%), fetal/pediatric cardiologists (85; 83.3%) or cardiac surgeons (49; 48.0%), other professionals (clinical geneticists, cardiac liaison nurses, fetal medicine midwives, psychologists, neonatologists and neuropediatricians) being involved less frequently. Most respondents to the questionnaire were fully aware of the link between CHD and NND, with only six (4%) being completely unaware (Figure 2). Awareness was more pronounced among pediatric cardiologists than among fetal medicine experts.

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669

60 49

40 Replies (%)

Number of replies

50 40 30

22

20 10 0

47.6%

50

10

10 5

7

20.4% 11.6%

0

6

2

0

In cases of In cases of TGA or HLHS HLHS Reply

No

20 10

15

10 12

29.3%

30

Yes

Figure 3 Breakdown of replies to the question, ‘Do you mention this risk to the parents of a fetus with congenital heart disease?’, according to specialty of respondent. , pediatric cardiologist; , fetal medicine expert; , other, e.g. radiologist, neonatologist. HLHS, hypoplastic left heart syndrome; TGA, transposition of the great arteries.

6.1%

Reply A

Reply B

Reply C

Reply D

Figure 5 Breakdown of replies to the question, ‘What sentence describes best your opinion on this issue? (you may tick more than one answer)’. Reply A, ‘the evidence is overwhelming, and we cannot but mention it in counseling’; Reply B, ‘there is some evidence, but it refers mainly to MRI modifications, not sure how much these determine actual neurodevelopmental delay’; Reply C, ‘there is some evidence, but in my experience I do not see as many cases of neurodevelopmental delay as expected according to the literature’; Reply D, ‘I will ignore it until the evidence becomes compelling’; Reply E, other. 35

7.4%

33

33

59.3%

Number of replies

30

11.1%

22.2%

Reply E

25 20

20 14

15

8

5 1

0

12 10

10 2

No

1

3 1

0

In cases of HLHS

2

In cases of TGA or HLHS

6 1

Yes

Reply

Figure 4 Breakdown of replies to the question, ‘If you do not mention this risk to the parents of a fetus with congenital heart disease, why?’. Replies: , ‘not convinced it impacts on actual life of the individuals’; , ‘feel more clear cut demonstration is needed before including this in counseling’; , ‘because otherwise most couples will opt for termination of pregnancy’; , ‘other’; further detail given in ‘other’ replies are summarized in Table S2.

The majority (82%) of healthcare professionals conveyed to the parents prenatally information on the risk of NDD in babies with CHD, approximately half (49.3%) of them doing so regardless of the type of CHD and the remainder (32.4%) doing so in selected cases, depending on the lesion; 18.2% did not discuss it at all (Figure 3). The reasons for this are reported in Figure 4. In general, the doctors felt that the scientific data are not yet sufficiently robust as to warrant inclusion in their prenatal counseling for CHD. This attitude is confirmed in Figure 5, which shows that almost half of the doctors who answered the questionnaire felt that imaging findings were not yet convincingly linked to adverse neurodevelopmental outcome. One third of the responders felt that NDD was not as prevalent as some recent reports have suggested. There was a geographical difference in the attitude of the respondents towards prenatal counseling (P < 0.001; Figure 6). Thirty-three (92%) of the 36 respondents from North America mentioned the risk of possible NDD in

Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Figure 6 Breakdown of replies to the question, ‘Do you mention this risk to the parents of a fetus with congenital heart disease?’ according to geographical location of respondents. , North America; , South America; , Europe; , Asia. HLHS, hypoplastic left heart syndrome; TGA, transposition of the great arteries.

CHD routinely, regardless of its type, whereas in Europe 33/79 (42%) and in Asia 6/27 (22%) respondents gave this information to all expectant parents. The strength with which the concept is conveyed during counseling by those who do so can be gauged by considering the replies reported in Table S1. The majority of respondents reported that prenatal brain MRI was not performed in fetuses with CHD (99/146 respondents; 67.8%); almost one third (44/146) of respondents said it was performed in selected cases, while only three (2.1%) said it was performed routinely. The timing of the fetal MRI was specified by 45 respondents; it was performed at 29–32 gestational weeks in most centers (19/45 (42.2%)), between 33 and 35 gestational weeks in 11 (24.4%), before 28 weeks in nine (20.0%) and after 35 gestational weeks in the remaining six (13.3%). The majority (98/143 (68.5%)) of respondents reported that presurgical brain MRI was not performed, while 41/143 (28.7%) stated that it was performed in

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selected cases only; only four (2.8%) respondents said it was performed routinely. The pediatric cardiology respondents were asked to state the timing of any neurological developmental assessment. Eighty-six replies were received: 32 (37.2%) reported that no specific assessment is performed in their center, 29 (33.7%) said it was done in selected cases only, while 25 (29.1%) stated that in their center a developmental assessment was carried out routinely in all neonates with CHD. Of the 41 centers in which specific neurodevelopmental assessment was carried out, 28 organized at least three serial assessments, at ages between 6 months and 5 years and above, and 13 centers organized only a single neurodevelopmental assessment of their patients, at 6 months (n = 3), 7–12 months (n = 2), 12–36 months (n = 6) or 60 months and above (n = 2).

Food for thought Most experts responding to this survey were aware of the association between brain damage and CHD but were less convinced that the imaging and metabolic findings on MRI and spectroscopy are robust markers of NDD in a particular fetus. Twelve percent of fetal/pediatric cardiologists and 24% of fetal medicine experts did not counsel families about the association of CHD and NDD. We found marked geographical differences in attitudes to prenatal counseling regarding NDD in CHD. It is interesting to note the low levels of TOP in North America compared with those in European countries and Asia despite the high percentage of North American centers counseling on NDD (Figure 1). In Europe and Asia, healthcare professionals were more reluctant to discuss NDD and when they did so, they tended to confine it to cases of HLHS and TGA. Possible explanations for their reluctance include the perception that most data refer to MRI changes which may not in fact be markers of actual NDD, and the personal opinions of senior professionals with broad experience in the long-term follow-up of individuals with CHD who do not recognize in their everyday experience the high incidence of NDD reported in the literature. Finally, they fear – at least in Europe, where TOP rates are higher than those in North America – that mention of this risk, which in their opinion remains to be confirmed by robust data, may lead to a further increase in the rate of TOP (Figure 4). Few centres participating in this survey worldwide had a protocol in place to investigate brain development in fetuses with CHD or their neonatal neurodevelopmental outcome. The key strength of this survey is that we apparently reached the correct target audience: 1) the sample of replies received was predominantly from the two leading disciplines involved in prenatal counseling for CHD, i.e. fetal/pediatric cardiologists and fetal medicine experts; 2) the number of CHD cases seen prenatally was high in most centers (70% saw > 50 cases of fetal CHD per year). Limitations include the inherent bias in respondents

Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

to online surveys, the fact that this survey did not cover, nor did it claim to cover, all referral centers worldwide, and the fact that only 150 (50%) replies were received to the 297 emails sent originally.

Conclusions The possibility of an association between HLHS and NDD was acknowledged in most of the replies to our questionnaire, but at the same time it was felt, especially in European centers, that more data are needed to quantify the risk and to identify factors associated with NDD in babies affected by TGA and other heart defects likely to have a biventricular circulation (Figure 6). Furthermore, studies of the association between CHD and NDD, particularly those that include longer term outcomes, do not usually state whether the diagnosis was prenatal or postnatal, nor whether the baby was delivered in optimal circumstances. Lack of prenatal diagnosis and delivery outside an expert cardiac center are important contributors to hypoxic brain insult. These factors contribute to a reluctance by many fetal cardiologists to include this information in prenatal counseling. Moreover, fetal MRI findings such as reduced brain biometry and delayed sulcation are not necessarily indicative of NND, and longitudinal studies into childhood for fetuses with all types of CHD would assist in strengthening the evidence base to guide prenatal management. In the meantime, there is a strong need worldwide to adjust the way in which information on NDD is transmitted to families during prenatal counseling. This topic will be addressed shortly by a Task Force of the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), which includes, among others, all the authors of the present article. Another issue to consider is our current and future ability to assess neurodevelopment. Equipment and personnel are expensive and clinical centers caring for individuals affected by CHD remain under-resourced; most babies only gain access to brain MRI and neurodevelopmental assessment through programs funded by research grants, which are, by their very nature, transient. Consequently, few centers had a protocol to investigate brain development in fetuses and neonates, despite the recommendations of a document by the American Heart Association underscoring the need for clinical surveillance of neonates and infants with CHD17 . Specialized equipment, technical expertise and research time are requirements for a successful program. Clinical standards of care should emphasize the importance of assessing neurodevelopment in all neonates affected with CHD, followed by the development of protocols that are funded and available to all. An expert panel could formulate these clinical care standards, list suitable investigations and recommend ideal timings (for example, pre- and post-surgery). Imaging should include both ultrasound and MRI, and serial clinical neurological development tests, such as the Bayley Scales of Infant Development score, should be applied.

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REFERENCES ¨ ¨ 1. Hovels-G urich HH, Seghaye MC, Schnitker R, Wiesner M, Huber W, Minkenberg R, Kotlarek F, Messmer BJ, von Bernuth G. Long-term neurodevelopmental outcomes in school-aged children after neonatal arterial switch operation. J Thorac Cardiovasc Surg 2002; 124: 448–458. 2. Bellinger DC, Wypij D, Rivkin MJ, DeMaso DR, Robertson RL Jr, Dunbar-Masterson C, Rappaport LA, Wernovsky G, Jonas RA, Newburger JW. Adolescents with d-transposition of the great arteries corrected with the arterial switch procedure: neuropsychological assessment and structural brain imaging. Circulation 2011; 124: 1361–1369. 3. Mitchell ME, Ittenbach RF, Gaynor JW, Wernovsky G, Nicolson S, Spray TL. Intermediate outcomes after the Fontan procedure in the current era. J Thorac Cardiovasc Surg 2006; 131: 172–180. 4. Shillingford A, Glanzman MM, Ittenbach RF, Clancy RR, Gaynor JW, Wernovsky G. Inattention, hyperactivity, and school performance in a population of school-age children with complex congenital heart disease. Pediatrics 2008; 121: 759–767. 5. Chen CY, Zimmerman RA, Faro S, Parrish B, Wang Z, Bilaniuk LT, Chou TY. MR of the cerebral operculum: topographic identification and measurement of interopercular distances in healthy infants and children. Am J Neuroradiol 1995; 16: 1677–1687. 6. Gaynor JW, Wernovsky G, Jarvik GP, Bernbaum J, Gerdes M, Zackai E, Nord AS, Clancy RR, Nicolson SC, Spray TL. Patient characteristics are important determinants of neurodevelopmental outcome at one year of age after neonatal and infant cardiac surgery. J Thorac Cardiovasc Surg 2007 May; 133: 1344–1353, 1353.e1–3. 7. Kaltman JR, Di H, Tian Z Rychik J. Impact of congenital heart disease on cerebrovascular blood flow dynamics in the fetus. Ultrasound Obstet Gynecol 2005; 25: 32–36. 8. Licht DJ, Shera DM, Clancy RR, Wernovsky G, Montenegro LM, Nicolson SC, Zimmerman RA, Spray TL, Gaynor JW, Vossough A. Brain maturation is delayed in infants with complex congenital heart defects. J Thorac Cardiovasc Surg 2009; 137: 529–536. 9. Shillingford AJ, Ittenbach RF, Marino BS, Rychik J, Clancy RR, Spray TL, Gaynor JW, Wernovsky G. Aortic morphometry and microcephaly in hypoplastic left heart syndrome. Cardiol Young 2007; 17: 189–195. 10. Sun L, Macgowan CK, Sled JG, Yoo SJ, Manlhiot C, Porayette P, Grosse-Wortmann L, Jaeggi E, McCrindle BW, Kingdom J, Hickey E, Miller S, Seed M. Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease. Circulation 2015; 131: 1313–1323. 11. Andropoulos DB, Hunter JV, Nelson DP, Stayer SA, Stark AR, McKenzie, Heinle JS, Fraser CD. Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high-flow bypass and cerebral oxygenation monitoring. J Thorac Cardiovasc Surg 2010 Mar; 139: 543–556.

671 12. Galli KK, Zimmerman RA, Jarvik GP, Wernovsky G, Kuypers MK, Clancy RR, Montenegro LM, Mahle WT, Newman MF, Saunders AM, Nicolson SC, Spray TL, Gaynor JW. Periventricular leukomalacia is common after neonatal cardiac surgery. J Thorac Cardiovasc Surg 2004; 127: 692–704. 13. Miller S, McQuillen PS, Hamrick S, Xu D, Glidden DV, Charlton N, Karl T, Azakie A, Ferriero DM, Barkovich AJ, Vigneron DB. Abnormal brain development in newborns with congenital heart disease. N Engl J Med 2007; 357: 1928–1938. ¨ 14. Sarajuuri A, Joniken E, Mildh L, Tujulin AM, Mattila I, Valanne L, Lonnqvist T. Neurodevelopmental burden at age 5 years in patients with univentricular heart. Pediatrics 2012; 130: e1636–1646. 15. Donofrio MT, Duplessis AJ, Limperopoulos C. Impact of congenital heart disease on fetal brain development and injury. Curr Opin Pediatr 2011; 23: 502–511. 16. Khalil A, Suff N, Thilaganathan B, Hurrell A, Cooper D, Carvalho JS. Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis. Ultrasound Obstet Gynecol 2014; 43: 14–24. 17. Marino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M, Gaynor JW. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation 2012; 126: 1143–1172. 18. Ortinau C, Alexopoulos D, Dierker D, Van Essen D, Beca J, Inder T. Cortical folding is altered before surgery in infants with congenital heart disease. J Pediatr 2013; 163: 1507–1510. 19. Clouchoux C, du Plessis AJ, Bouyssi-Kobar M, Tworetzky W, McElhinney DB, Brown DW, Gholipour A, Kudelski D, Warfield SK, McCarter RJ, Robertson LJ Jr, Evans AC, Newburger JW, Limperopoulos C. Delayed cortical development in fetuses with complex congenital heart disease. Cereb Cortex 2012; 23: 2932–2943. 20. Limperopoulos C, Tworetzky W, McElhinney DB, Newburger JW, Brown DW, Robertson RL Jr, Guizard N, McGrath E, Geva J, Annese D, Dunbar-Masterson C, Trainor B, Laussen PL, du Plessis AJ. Brain volume and metabolism in foetuses with congenital heart disease: evaluation with quantitative magnetic resonance imaging and spectroscopy. Circulation 2010; 121: 26–33. 21. Mlczoch E, Brugger P, Ulm B, Novak A, Frantal S, Prayer D, Salzer-Muhar U. Structural congenital brain disease in congenital heart disease: results from a fetal MRI program. Eur J Paediatr Neurol 2013 Mar; 17: 153–160. 22. Owen M, Shevell M, Majnemer A, Limperopoulos C. Abnormal brain structure and function in newborns with complex congenital heart defects before open heart surgery a review of the evidence. J Child Neurol 2011; 26: 743–755. 23. Martinez-Biarge M, Jowett VC, Cowan FM, Wusthoff CJ. Neurodevelopmental outcome in children with congenital heart disease. Semin Fetal Neonatal Med 2013; 18: 279–285.

SUPPORTING INFORMATION ON THE INTERNET The following supporting information may be found in the online version of this article: Appendix S1 Questionnaire and its rationale, circulated among centers for fetal congenital heart disease (CHD) worldwide, to gather information on healthcare professionals’ practice, their understanding of the evidence base for neurodevelopmental delay in CHD and the way in which they convey this information during prenatal counseling. Table S1 Selected strings entered in the free-text slot for ‘can you write how you mention this risk, to let us perceive the strength with which you convey this piece of information to the couple? (e.g. ‘in some cases, MRI evidence of brain lesions has been reported’, or other)’ (88 replies) Table S2 Summary of replies to the question, ‘If you do not mention this risk to the parents of a fetus with congenital heart disease, why?’

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Ultrasound Obstet Gynecol 2016; 47: 667–671.