Development of standard definitions and grading for Maternal and Fetal Adverse Event Terminology.

OBJECTIVE: Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive framework to define and grade maternal and fetal AEs in pregnancy trials severely limits understanding risks in pregnant women. We created AE terminology to improve safety monitoring for developing pregnancy drugs, devices and interventions. METHOD: Existing severity grading for pregnant AEs and definitions/indicators of 'severe' and 'life-threatening' conditions relevant to maternal and fetal clinical trials were identified through a literature search. An international multidisciplinary group identified and filled gaps in definitions and severity grading using Medical Dictionary for Regulatory Activities (MedDRA) terms and severity grading criteria based on Common Terminology Criteria for Adverse Event (CTCAE) generic structure. The draft criteria underwent two rounds of a modified Delphi process with international fetal therapy, obstetric, neonatal, industry experts, patients and patient representatives. RESULTS: Fetal AEs were defined as being diagnosable in utero with potential to harm the fetus, and were integrated into MedDRA. AE severity was graded independently for the pregnant woman and her fetus. Maternal (n = 12) and fetal (n = 19) AE definitions and severity grading criteria were developed and ratified by consensus. CONCLUSIONS: This Maternal and Fetal AE Terminology version 1.0 allows systematic consistent AE assessment in pregnancy trials to improve safety.

Fetal Cardiac Intervention for Pulmonary Atresia with Intact Ventricular Septum: International Fetal Cardiac Intervention Registry.

INTRODUCTION: Invasive fetal cardiac intervention (FCI) for pulmonary atresia with intact ventricular septum (PAIVS) and critical pulmonary stenosis (PS) has been performed with small single-institution series reporting technical and physiological success. We present the first multicenter experience. OBJECTIVES: Describe fetal and maternal characteristics of those being evaluated for FCI, including pregnancy/neonatal outcome data using the International Fetal Cardiac Intervention Registry (IFCIR). METHODS: We queried the IFCIR for PAIVS/PS cases evaluated from January 2001 to April 2018 and reviewed maternal/fetal characteristics, procedural details, pregnancy and neonatal outcomes. Data were analyzed using standard descriptive statistics. RESULTS: Of the 84 maternal/fetal dyads in the registry, 58 underwent pulmonary valvuloplasty at a median gestational age of 26.1 (21.9-31.0) weeks. Characteristics of fetuses undergoing FCI varied in terms of tricuspid valve (TV) size, TV regurgitation, and pulmonary valve patency. There were fetal complications in 55% of cases, including 7 deaths and 2 delayed fetal losses. Among those who underwent successful FCI, the absolute measurement of the TV increased by 0.32 (±0.17) mm/week from intervention to birth. Among 60 liveborn with known outcome, there was a higher percentage having a biventricular circulation following successful FCI (87 vs. 43%). CONCLUSIONS: Our data suggest a possible benefit to fetal therapy for PAIVS/PS, though rates of technically unsuccessful procedures and procedure-related complications, including fetal loss were substantial. FCI criteria are extremely variable, making direct comparison to nonintervention patients challenging and potentially biased. More uniform FCI criteria for fetuses with PAIVS/PS are needed to avoid unnecessary procedures, expose only fetuses most likely to sustain a benefit, and to enable comparisons to be made with nonintervention patients.

Procedural, pregnancy, and short-term outcomes after fetal aortic valvuloplasty.

OBJECTIVES: We aimed to evaluate the effect of technical aspects of fetal aortic valvuloplasty (FAV) on procedural risks and pregnancy outcomes. BACKGROUND: FAV is performed in cases of severe mid-gestation aortic stenosis with the goal of preventing hypoplastic left heart syndrome (HLHS). METHODS: The International Fetal Cardiac Intervention Registry was queried for fetuses who underwent FAV from 2002 to 2018, excluding one high-volume center. RESULTS: The 108 fetuses had an attempted cardiac puncture (mean gestational age [GA] 26.1 ± 3.3 weeks). 83.3% of attempted interventions were technically successful (increased forward flow/new aortic insufficiency). The interventional cannula was larger than 19 g in 70.4%. More than one cardiac puncture was performed in 25.0%. Intraprocedural complications occurred in 48.1%, including bradycardia (34.1%), pericardial (22.2%) or pleural effusion (2.7%) requiring drainage, and balloon rupture (5.6%). Death within 48 hr occurred in 16.7% of fetuses. Of the 81 patients born alive, 59 were discharged home, 34 of whom had biventricular circulation. More than one cardiac puncture was associated with higher complication rates (p < .001). Larger cannula size was associated with higher pericardial effusion rates (p = .044). On multivariate analysis, technical success (odds ratio [OR] = 10.9, 95% confidence interval [CI] = 2.2-53.5, p = .003) and later GA at intervention (OR = 1.5, 95% CI = 1.2-1.9, p = .002) were associated with increased odds of live birth. CONCLUSIONS: FAV is an often successful but high-risk procedure. Multiple cardiac punctures are associated with increased complication and fetal mortality rates. Later GA at intervention and technical success were independently associated with increased odds of live birth. However, performing the procedure later in gestation may miss the window to prevent progression to HLHS.

Clinical Monitoring of Sacrococcygeal Teratoma.

BACKGROUND: Sacrococcygeal teratomas (SCT) are often highly vascularized and may result in high-output cardiac failure, polyhydramnios, fetal hydrops, and demise. Delivery is guided by the SCT to fetus volume ratio (SCTratio), SCT growth rate, and cardiac output indexed for weight (CCOi). METHODS: We compared measurements and outcome in 12 consecutive fetuses referred with SCT. Adverse outcomes were: fetal surgery, delivery < 32 gestational weeks or neonatal demise. Only SCTratio and CCOi were used to manage the cases. SCT vascularization index (VI%) was derived from the 3D virtual organ computer-aided analysis (VOCAL) software. The SCTModel (modified from acardiac twins) calculated a hypothetical SCT draining vein size and derived a risk line, using diameters of the superior and inferior vena cava, the azygous and umbilical veins. VI% and a model of systemic and umbilical venous volumes (SCTModel) were tested as indicators for outcome in SCT. RESULTS: Fetuses were monitored from 20.1 to 36.4 gestational weeks and 5/12 had adverse outcomes: 1 had successful open fetal surgery at 23.8 weeks and delivered at term, 4 delivered at < 32 weeks with 3/4 having neonatal demise between 25 and 29 weeks. VI% was significantly higher in cases with adverse outcomes (mean 10.3 [8.9-11.6] vs. 4.4 [3.4-5.3], p < 0.0001). The additional fraction of the fetal cardiac output required to perfuse the SCT-draining vein (XSCO%) (p = 0.46), SCTratio (p = 0.08), and CCOi (p = 0.64) were not significant. All cases with adverse outcome had VI% > 8%. The SCTModel risk line predicted nonadverse outcomes well but lacked data in 2/5 cases with adverse outcomes. CONCLUSIONS: VI% is a significant indicator of SCT cases with adverse outcomes and combined with SCTratio may guide timing of delivery better than current measures.

In utero intervention for severe congenital heart disease.

The aim of foetal cardiac therapy is to treat an abnormality at the developmental stage so that the process of cardiac growth, which is complex and relies on the volume and direction of circulating blood as well as genetic determinants, can continue. In reality, most cardiac interventions are palliative; hence, major abnormalities are still present at birth. Nevertheless, tangible benefits following successful foetal intervention include improved haemodynamics and reduction in secondary damage leading to better postnatal outcomes. In cases of semilunar valve stenosis, or atresia, foetal valvuloplasty aims to achieve a biventricular, rather than univentricular, circulation. Opening and stenting a restrictive atrial foramen may preserve the pulmonary function in cases of hypoplastic left heart syndrome, thereby increasing the chances of successful postnatal surgery. More recent endeavours include percutaneous implantation of a miniaturised pacemaker to treat complete heart block and the promotion of left-sided heart growth by chronic maternal hyperoxygenation. The true clinical benefit of these interventions over natural history remains uncertain because of the paucity of appropriate randomised controlled trials (RCTs). Foetal cardiac therapy must now move from a pioneering approach to one that is supported by evidence, as has been done successfully for other foetal therapies.

Attitudes of clinicians toward cardiac surgery and trisomy 18.

Trisomy 18 is an autosomal trisomy condition characterized by minor to major birth defects, severe disabilities, and high rates of pre- and postnatal mortality. Interventions for these infants have traditionally been withheld with focus instead on palliative support. The issues and attitudes surrounding corrective surgery of congenital heart defects, which is a birth defect that occurs in approximately 90% of infants with trisomy 18, is of our study's interest as recent literature has indicated that cardiac surgery is being performed and may lead to improved survival compared to palliative care. Thus, our study aimed to describe clinician attitudes toward cardiac surgery and trisomy 18. We surveyed 378 clinicians from multiple specialties, including genetic counselors, involved in the pre- and postnatal care of infants with trisomy 18. Descriptive statistics were performed to describe all clinicians' responses, and a secondary analysis with stratifications by clinician type was also performed. Forty-eight percent (n = 378) of clinicians felt it was appropriate to discuss the option of cardiac surgery. Ethical concerns and insufficient outcome data were the most agreed upon reasons for not offering cardiac surgery. Trisomy 18 not being uniformly lethal and expressed parental wishes were the most agreed upon justifications for offering surgery. Clinicians felt the discussion of the option of cardiac surgery is appropriate, however are hesitant due to ethical concerns and insufficient outcome data. Results from this study aim to promote discussion and collaboration among clinicians to improve consistency in patient care.

Home Monitoring for Fetal Heart Rhythm During Anti-Ro Pregnancies.

BACKGROUND: Fetal atrioventricular block (AVB) occurs in 2% to 4% of anti-Ro antibody-positive pregnancies and can develop in <24 h. Only rarely has standard fetal heart rate surveillance detected AVB in time for effective treatment. OBJECTIVES: Outcome of anti-Ro pregnancies was surveilled with twice-daily home fetal heart rate and rhythm monitoring (FHRM) and surveillance echocardiography. METHODS: Anti-Ro pregnant women were recruited from 16 international centers in a prospective observational study. Between 18 and 26 weeks' gestation, mothers checked FHRM twice daily with a commercially available Doppler monitor and underwent weekly or biweekly surveillance fetal echocardiograms. If FHRM was abnormal, a diagnostic echocardiogram was performed. Cardiac cycle length and atrioventricular interval were measured, and cardiac function was assessed on all echocardiograms. After 26 weeks, home FHRM and echocardiograms were discontinued, and mothers were monitored during routine obstetrical visits. Postnatal electrocardiograms were performed. RESULTS: Most mothers (273 of 315, 87%) completed the monitoring protocol, generating 1,752 fetal echocardiograms. Abnormal FHRM was detected in 21 mothers (6.7%) who sought medical attention >12 h (n = 7), 3 to 12 h (n = 9), or <3 h (n = 5) after abnormal FHRM. Eighteen fetuses had benign rhythms, and 3 had second- or third-degree AVB. Treatment of second-degree AVB <12 h after abnormal FHRM restored sinus rhythm. Four fetuses had first-degree AVB diagnosed by echocardiography; none progressed to second-degree AVB. No AVB was missed by home FHRM or developed after FHRM. CONCLUSIONS: Home FHRM confirms the rapid progression of normal rhythm to AVB and can define a window of time for successful therapy. (Prospective Maternal Surveillance of SSA [Sjögren Syndrome A] Positive Pregnancies Using a Hand-held Fetal Heart Rate Monitor; NCT02920346).

Long-term outcomes for monochorionic twins after laser therapy in twin-to-twin transfusion syndrome.

Twin-to-twin transfusion syndrome typically occurs in the second trimester in 10-15% of monochorionic twin pregnancies. Vascular anastomoses of monochorionic placentae are the underlying cause of the development of the syndrome. If a blood flow imbalance occurs, one fetus becomes the so-called donor twin and the other the recipient. If untreated, perinatal mortality is 80-90%. Fetoscopic laser coagulation of the vascular anastomoses destroys the cause of the syndrome and leads to dual twin survival rates of around 70% and more than 90% of pregnancies with at least one survivor. However, unequal placental sharing, intrauterine death, and severe prematurity are still limiting factors for further improvement of survival rates and decreases in long-term morbidity. Prematurity and neurodevelopmental impairment affect the donor and recipient twins, whereas cardiovascular failure and obstruction of the right ventricular outflow tract are typical complications of recipients, which can lead to long-term morbidity. In this Review, we summarise the literature on follow-up data for survivors of twin-to-twin-transfusion syndrome after laser therapy, including neurodevelopmental outcomes, cardiovascular outcomes, growth, renal function, and ischaemic events, as well as the potential effects of intrauterine programming on later life.

The Influence of Blood Pressure on Fetal Aortic Distensibility: An Animal Validation Study.

BACKGROUND/AIMS: Aortic distension waveforms describe the change in diameter or cross-sectional area over the cardiac cycle. We aimed to validate the association of aortic fractional area change (AFAC) with blood pressure (BP) in a fetal lamb model. METHODS: Four pregnant ewes underwent open fetal surgery under general anesthesia at 107-120 gestational days. A 4-Fr catheter was introduced into the fetal femoral artery and vein, or the carotid artery and jugular vein. The thoracic aorta was imaged using real-time ultrasound; AFAC was calculated using offline speckle tracking software. Measurements of invasive BP and AFAC were obtained simultaneously and averaged over 10 cardiac cycles. BP was increased by norepinephrine infusion and the association of aortic distensibility with BP was assessed. RESULTS: Baseline measurements were obtained from 4 lambs, and changes in aortic distensibility with increasing BP were recorded from 3 of them. A positive correlation was found between AFAC and systolic BP (r = 0.692, p = 0.001), diastolic BP (r = 0.647, p = 0.004), mean BP (r = 0.692, p = 0.001), and BP amplitude (r = 0.558, p = 0.016) controlled for heart rate. No association was found between BP and maximum or minimum aortic area. CONCLUSION: AFAC provides a quantifiable measure of aortic distensibility and correlates with systolic BP, diastolic BP, mean BP, and BP amplitude in a fetal lamb model.

Advances in fetal echocardiography.

The development of fetal echocardiography and success in prenatal cardiac screening programs over the past 30 years has been driven by technical innovation and influenced by the different approaches of the various specialties practicing it. Screening for congenital heart defects no longer focuses on examining a limited number of pregnant women thought to be at increased risk, but instead forms an integrated part of a high-quality anatomical ultrasound performed in the second trimester using the 'five-transverse view' protocol. A prenatal diagnosis is feasible in almost all cardiac lesions and the advantages to parents and to health professionals are well recognized. Prenatal evaluation can usually determine the level of care required at delivery, thereby reducing perinatal morbidity. However, only half of the babies undergoing surgery within the first year of life have a prenatal detection, and practical training programs to support and provide feedback to sonographers remain essential for continued improvement.

Recipient umbilical artery elongation (redundancy) in twin-twin transfusion syndrome.

BACKGROUND: Chronic hypertension in adults causes arterial lengthening in major arteries, but the effects of early fetal hypertension on the twin-twin transfusion syndrome recipient's vascular architecture remains unknown. OBJECTIVE: We hypothesize that arterial cord redundancy is related to recipient hypertension and subsequent heart failure. Our objectives were to: (1) establish a 3-dimensional color Doppler ultrasound method of measuring umbilical arterial length relative to its corresponding venous segment in the umbilical cord using artery vein angle; (2) compare recipient artery vein angle to gestational age-matched controls; and (3) test the association of artery vein angle with recipient heart failure. STUDY DESIGN: We compared 3 groups prospectively: twin-twin transfusion syndrome pregnancies undergoing fetoscopic laser surgery (preoperatively) and 2 groups of gestational age-matched controls: uncomplicated monochorionic-diamniotic twin pregnancies and healthy singletons. Using a 3-dimensional color-Doppler volume image of 5 cm of cord near the placental insertion, we traced the umbilical artery and vein producing umbilical artery:vein length, (artery vein index) and measured the artery vein angle between umbilical artery and vein. Correlation of artery vein angle to twin-twin transfusion syndrome stage, maximum vertical pocket, umbilical arterial indices, ductus venosus Doppler, and brain natriuretic peptide were performed. We used pulsed-wave and tissue Doppler to measure tissue Doppler velocities and indexed cardiac output and correlated these with artery vein angle. Comparative statistics, including multivariable linear regression, examined the relationship between umbilical arterial Doppler indices and artery vein angle. RESULTS: Artery vein angle and artery vein index correlated significantly (R2, 0.86; P < .0001), hence, artery vein angle was used for analysis. Mean artery vein angle was 33.1 ± 31.5 degrees in recipients (n = 44), 9.5 ± 6 degrees in monochorionic-diamniotic (n = 11; 22 fetuses), and 8.9 ± 8.3 degrees in singleton controls (n = 16) (P < .001). An artery vein angle ≥26 degrees (>95th percentile for controls) was measured in 52% recipients. Artery vein angle was higher in twin-twin transfusion syndrome stage 3R vs 1 (P = .001). Artery vein angle increased with increasing umbilical arterial pulsatility index (P < .001), and decreased with increasing resistance index (P = .02) after adjusting for gestational age. Interrater agreements to categorize abnormal artery vein angle values was 95% (P < .001). Abnormal ductus venosus Doppler and elevated recipient amniotic fluid N-terminal pro-brain natriuretic peptide/protein levels correlated significantly with artery vein angle. Abnormal artery vein angles were associated with decreased indexed cardiac output, lower tissue Doppler velocities, higher right-sided Tei indices, and severe tricuspid regurgitation. CONCLUSION: Umbilical arterial lengthening occurs in 52% of recipients and is associated with abnormal Doppler flows, low systolic tissue Doppler velocities, reduced cardiac output, and elevated markers of cardiac failure. This may reflect chronicity and severity of hypertension in the recipient fetus. Further research is needed to explore the mechanisms of elongation and long-term implications.

Acardiac twin pregnancies part IV: Acardiac onset from unequal embryonic splitting simulated by a fetoplacental resistance model.

BACKGROUND: Benirschke postulated that acardiac twinning occurs when markedly unequal embryonic splitting combines with arterioarterial (AA) and venovenous placental anastomoses. We tested this hypothesis by model simulations and by comparison of outcomes with 18 "pseudo-" (twin fetus with beating heart but otherwise with clear signs of an acardiac) and 3 "normal" acardiac cases. METHODS: The smaller/larger cell volume ratio at embryonic splitting becomes the smaller/larger embryonic/fetal blood volume ratio (a). From a, we derived nonpulsating blood pressures using normal values (larger twin) and normal values at an appropriate earlier gestational age (smaller twin). These unequal pressure sources were used in a linear resistance fetoplacental network to calculate umbilical venous diameter ratios. Acardiac onset occurs when the smaller twin has 50% left of its normal, singleton placenta. Comparison with clinical cases approximated a by crown-rump-length-ratio to the 3rd power. Input parameters are a and the AA-radius at 40 weeks. RESULTS: Acardiacs can be small or large, can occur early or late, earlier at smaller a and larger AA, with larger umbilical venous diameter ratios at smaller a and smaller AA. Comparison with the 21 clinical cases was good, except for 2. CONCLUSION: Our analysis supports Benirschke's hypothesis. The smaller twin has to share its placental perfusion with the larger twin, which is a novel finding. The AA size is essential for the future of both fetuses but complicates easy understanding of (pseudo-)acardiac clinical presentations. Late acardiac onset occurs infrequently. Using nonpulsating circulations may have caused our extensive predictions of late onset. An improved model requires including hypoxemia in the smaller twin from chronic placental hypoperfusion. Birth Defects Research 109:211-223, 2017. © 2016 Wiley Periodicals, Inc.

Acardiac twin pregnancies part II: Fetal risk of chorangioma and sacrococcygeal teratoma predicted by pump/acardiac umbilical vein diameters.

BACKGROUND: We recently published pump/acardiac umbilical venous diameter (UVD) ratios, representing the pump twin's excess cardiac output fraction, of 27 acardiac twin pregnancies. There was a clear separation between the 17 pump twins that had life-threatening complications and the 10 that did not. The hypothesis of this study is that placental chorangioma and sacrococcygeal teratoma (SCT), tumors whose perfusion also causes high-output complications, have the same fetal outcome as pump twins when perfusion of the tumor requires the same excess cardiac output fraction. METHODS: We compared the three fetoplacental circulations. Fetuses with a placental chorangioma and acardiac twin pregnancies both have their feeding artery and draining vein located at the placental cord insertion. In contrast, SCT lacks a prescribed feeding artery and draining vein. We, therefore, had to modify our model to assume that the diameter of the hypothetical draining vein is related to the flow difference between inferior vena cava and superior vena cava. The latter flow has been estimated sonographically and is the same as the inferior vena cava flow in the absence of an SCT. Furthermore, a simple modification accounts for the different location of the tumor with respect to the placental cord insertion. RESULTS: We propose to apply the clinical pump/acardiac UVD ratios to pregnancies complicated by placental chorangiomas and the modified pump/acardiac UVD ratios for SCT. CONCLUSION: Risk prediction of these rare fetal tumors may be possible based on application of data on excess cardiac output fractions from pump/acardiac UVD ratios and will require future clinical validation. Birth Defects Research (Part A) 106:733-738, 2016. © 2016 Wiley Periodicals, Inc.

Fetal cardiovascular hemodynamics in twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) complicates 10-15% of monochorionic-diamniotic (MCDA) pregnancies. It originates from unbalanced transfer of fluid and vasoactive mediators from one twin to its co-twin via placental anastomoses. This results in hypovolemia in the donor and hypervolemia and vasoconstriction in the recipient twin. Consequently, the recipient demonstrates cardiovascular alterations including atrioventricular valve regurgitation, diastolic dysfunction, and pulmonary stenosis/atresia that do not necessarily correlate with Quintero-stages. Selective fetoscopic laser photocoagulation of placental vascular anastomoses disrupts the underlying pathophysiology and usually improves cardiovascular function in the recipient with normalization of systolic and diastolic function within weeks after treatment. Postnatal studies have demonstrated early decreased arterial distensibility in ex-donor twins, but 10-year follow up is encouraging with survivors showing normal cardiovascular function after TTTS. However, prediction and appropriate early management of TTTS remain poor. Assessment of the cardiovascular system provides additional insight into the pathophysiology and severity of TTTS and may permit more targeted early surveillance of MCDA pregnancies in future. It should form an integral part of the diagnostic algorithm.

Foetal cardiac function: assessing new technologies.

Assessment of foetal cardiac function is more challenging than in the adult, in whom emerging technologies are tested. The postnatal cardio-respiratory interaction is replaced by the cardio-placental circulation and impedance of the brain, and distal vascular beds play an important role in modulating flow to enable its redistribution in the foetal body. Prenatal specialists, comprising obstetricians and cardiologists, have tested a variety of traditional methodologies, as well as non-Doppler offline ultrasound methods in the foetus. This article reviews the development of techniques, outlines their use, and draws attention to pitfalls in adapting technologies validated in the adult heart to the small, fast beating, remote, and largely ungated foetal heart.

Foetal therapy, what works? An overview.

The update course in foetal cardiology held by the Fetal Working Group of the Association for European Paediatric and Congenital Cardiology in Istanbul in May 2012 included a session on foetal cardiac therapy. In the introductory overview to this symposium, we critically examine the level of evidence supporting or refuting proposed foetal cardiac therapies including transplacental treatment of foetal tachyarrhythmias, steroid treatment in foetal atrioventricular block, and foetal aortic valvuloplasty. In summary, the evidence for the efficiency and safety of currently available foetal cardiac therapies is low, with no therapy based on a randomised controlled trial. Transplacental treatment of foetal tachycardia is generally accepted as effective and safe, based on extensive and widespread clinical experience; however, there is no consensus on which drugs are the most effective in different electrophysiological situations. Randomised studies may be able to resolve this, but this is complicated because tachyarrhythmias are relatively rare conditions, the foetus is not accessible for direct treatment, and it is the healthy mother who accepts treatment she does not need on behalf of her foetus. The indications for steroid treatment in foetal atrioventricular block and for foetal valvuloplasty are even more controversial. Although randomised trials would be desirable, the practical issues of recruiting sufficient sample sizes and controlling for variation in practice across multiple sites is not to be underestimated. Multicentre registries, analysed free of bias, may be an alternative way to improve the evidence base of foetal cardiac therapy.

Prenatal screening for major congenital heart disease: assessing performance by combining national cardiac audit with maternity data.

OBJECTIVE: Determine maternity hospital and lesion-specific prenatal detection rates of major congenital heart disease (mCHD) for hospitals referring prenatally and postnatally to one Congenital Cardiac Centre, and assess interhospital relative performance (relative risk, RR). METHODS: We manually linked maternity data (3 hospitals prospectively and another 16 retrospectively) with admissions, fetal diagnostic and surgical cardiac data from one Congenital Cardiac Centre. This Centre submits verified information to National Institute for Cardiovascular Outcomes Research (NICOR-Congenital), which publishes aggregate antenatal diagnosis data from infant surgical procedures. We included 120 198 unselected women screened prospectively over 11 years in 3 maternity hospitals (A, B, C). Hospital A: colocated with fetal medicine, proactive superintendent, on-site training, case-review and audit, hospital B: on-site training, proactive superintendent, monthly telemedicine clinics, and hospital C: sonographers supported by local obstetrician. We then studied 321 infants undergoing surgery for complete transposition (transposition of the great arteries (TGA), n=157) and isolated aortic coarctation (CoA, n=164) screened in hospitals A, B, C prospectively, and 16 hospitals retrospectively. RESULTS: 385 mCHD recorded prospectively from 120 198 (3.2/1000) screened women in 3 hospitals. Interhospital relative performance (RR) in Hospital A:1.68 (1.4 to 2.0), B:0.70 (0.54 to 0.91), C:0.65 (0.5 to 0.8). Standardised prenatal detection rates (funnel plots) demonstrating inter-hospital variation across 19 hospitals for TGA (37%, 0.00 to 0.81) and CoA (34%, 0.00 to 1.06). CONCLUSIONS: Manually linking data sources produced hospital-specific and lesion-specific prenatal mCHD detection rates. More granular, rather than aggregate, data provides meaningful feedback to improve screening performance. Automatic maternal and infant record linkage on a national scale, requires verified, prospective maternity audit and integration of health information systems.

The cost-effectiveness of prenatal detection for congenital heart disease using telemedicine screening.

We estimated the longer-term cost-effectiveness of using telemedicine screening for prenatal detection of congenital heart disease (CHD). One hospital in south-east England with a telemedicine service was connected to a fetal cardiology unit in London. A UK health service perspective was adopted. Evidence on costs and outcomes for standard-risk pregnant women during the antenatal period was based on patient-level data. Extrapolation beyond the end of the study (just after delivery) was carried out for the lifetime of children born with and without CHD. Expert opinion and data from published sources was used to populate a decision model. Future costs and benefits were discounted. The main outcome was quality-adjusted life years (QALYs) and results were expressed as cost per QALY gained. Various one-way sensitivity analyses were conducted. The model showed that offering telemedicine screening by specialists to all standard-risk pregnant women was the dominant strategy (i.e. cheaper and more effective). The sensitivity analyses found that the model was robust, and that telemedicine remained the most cost-effective strategy. The study showed that it would be cost-effective to provide telemedicine examinations as part of an antenatal screening programme for all standard-risk women.