Risk of major congenital heart disease in pregestational maternal diabetes is modified by hemoglobin A1c.

OBJECTIVES: The association between pregestational diabetes mellitus (PDM) and risk of congenital heart disease (CHD) is well recognized; however, the importance of glycemic control and other coexisting risk factors during pregnancy is less clear. We sought to determine the relative risk (RR) of major CHD (mCHD) among offspring from pregnancies complicated by PDM and the effect of first-trimester glycemic control on mCHD risk. METHODS: We determined the incidence of mCHD (requiring surgery within 1 year of birth or resulting in pregnancy termination or fetal demise) among registered births in Alberta, Canada. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c) at < 16 weeks' gestation and other covariates was performed using data from the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted RR (aRR), calculated using log-binomial modeling. RESULTS: Of 1412 cases of mCHD in 594 773 (2.37/1000) births in the study period, mCHD was present in 48/7497 with PDM (6.4/1000; RR, 2.8 (95% CI, 2.1-3.7); P < 0.0001). In the entire cohort, increased maternal age (aRR, 1.03 (95% CI, 1.02-1.04); P < 0.0001) and multiple gestation (aRR, 1.37 (95% CI, 1.1-1.8); P = 0.02) were also associated with mCHD risk, whereas maternal prepregnancy weight > 91 kg was not. The stratified risk for mCHD associated with HbA1c ≤ 6.1%, > 6.1-8.0% and > 8.0% was 4.2/1000, 6.8/1000 and 17.1/1000 PDM/gestational diabetes mellitus births, respectively; the aRR of mCHD associated with PDM and HbA1c > 8.0% was 8.5 (95% CI, 5.0-14.4) compared to those without diabetes and 5.5 (95% CI, 1.6-19.4) compared to PDM with normal HbA1c (≤ 6.1%). CONCLUSIONS: PDM is associated with a RR of 2.8 for mCHD, increasing to 8.5 in those with HbA1c > 8%. These data should facilitate refinement of referral indications for high-risk pregnancy screening. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Treatment, not delivery, of the late preterm and term fetus with supraventricular arrhythmia.

OBJECTIVE: While in-utero treatment of sustained fetal supraventricular arrhythmia (SVA) is standard practice in the previable and preterm fetus, data are limited on best practice for late preterm (34 + 0 to 36 + 6 weeks), early term (37 + 0 to 38 + 6 weeks) and term (> 39 weeks) fetuses with SVA. We reviewed the delivery and postnatal outcomes of fetuses at ≥ 35 weeks of gestation undergoing treatment rather than immediate delivery. METHODS: This was a retrospective case series of fetuses presenting at ≥ 35 weeks of gestation with sustained SVA and treated transplacentally at six institutions between 2012 and 2022. Data were collected on gestational age at presentation and delivery, SVA diagnosis (short ventriculoatrial (VA) tachycardia, long VA tachycardia or atrial flutter), type of antiarrhythmic medication used, interval between treatment and conversion to sinus rhythm and postnatal SVA recurrence. RESULTS: Overall, 37 fetuses presented at a median gestational age of 35.7 (range, 35.0-39.7) weeks with short VA tachycardia (n = 20), long VA tachycardia (n = 7) or atrial flutter (n = 10). Four (11%) fetuses were hydropic. In-utero treatment led to restoration of sinus rhythm in 35 (95%) fetuses at a median of 2 (range, 1-17) days; this included three of the four fetuses with hydrops. Antiarrhythmic medications included flecainide (n = 11), digoxin (n = 7), sotalol (n = 11) and dual therapy (n = 8). Neonates were liveborn at 36-41 weeks via spontaneous vaginal delivery (23/37 (62%)) or Cesarean delivery (14/37 (38%)). Cesarean delivery was indicated for fetal SVA in two fetuses, atrial ectopy or sinus bradycardia in three fetuses and obstetric reasons in nine fetuses that were in sinus rhythm at the time of delivery. Twenty-one (57%) cases were treated for recurrent SVA after birth. CONCLUSION: In-utero treatment of the near term and term (≥ 35-week) SVA fetus is highly successful even in the presence of hydrops, with the majority of cases delivered vaginally closer to term, thereby avoiding unnecessary Cesarean section. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of rural residence and low socioeconomic status on rate and timing of prenatal detection of major congenital heart disease in a jurisdiction of universal health coverage.

OBJECTIVE: Socioeconomic status (SES) and distance of residence from tertiary care may impact fetal detection of congenital heart disease (CHD), partly through reduced access to and quality of obstetric ultrasound screening. It is unknown whether SES and remoteness of residence (RoR) affect prenatal detection of CHD in jurisdictions with universal health coverage. We examined the impact of SES and RoR on the rate and timing of prenatal diagnosis of major CHD within the province of Alberta in Canada. METHODS: In this retrospective study, we identified all fetuses and infants diagnosed with major CHD in Alberta, from 2008 to 2018, that underwent cardiac surgical intervention within the first year after birth, died preoperatively, were stillborn or underwent termination. Using maternal residence postal code and geocoding, Chan SES index quintile, geographic distance from a tertiary-care fetal cardiology center and the Canadian Index of Remoteness (IoR) were calculated. Outcome measures included rates of prenatal diagnosis and diagnosis after 22 weeks' gestation. Risk ratios (RR) were calculated using log-binomial regression and stratified by rural (≥ 100 km from tertiary care) or metropolitan (< 100 km from tertiary care) residence, adjusting for year of birth and the obstetric ultrasound screening view in which CHD would most likely be detected (four-chamber view; outflow-tract view; three-vessel or three-vessels-and-trachea or non-standard view; septal view). RESULTS: Of 1405 fetuses/infants with major CHD, prenatal diagnosis occurred in 814 (57.9%). Residence ≥ 100 km from tertiary care (adjusted RR, 1.19; 95% CI, 1.05-1.34) and higher IoR (adjusted RR, 1.9; 95% CI, 1.1-3.3) were associated with missed prenatal diagnosis of major CHD. Similarly, residence ≥ 100 km from tertiary care (adjusted RR, 1.41; 95% CI, 1.22-1.62) and higher IoR (adjusted RR, 3.6; 95% CI, 2.2-8.2) were associated with prenatal diagnosis after 22 weeks. Although adjusted and unadjusted analyses showed no association between Chan SES index quintile and prenatal-diagnosis rate overall nor for residence in rural areas, in metropolitan regions, lower SES quintiles were associated with missed prenatal diagnosis (quintile 1: RR, 1.24; 95% CI, 1.02-1.50) and higher risk of diagnosis after 22 weeks' gestation (quintile 1: RR, 1.46; 95% CI, 1.10-1.93; quintile 2: RR, 1.66; 95% CI, 1.24-2.23). CONCLUSIONS: Despite universal healthcare, rural residence in Alberta is associated with lower rate of prenatal diagnosis of major CHD and higher risk of late prenatal diagnosis (≥ 22 weeks). Within metropolitan regions, lower SES impacts negatively prenatal-diagnosis rate and timing. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Clinical presentation, genetic etiology and outcome associated with fetal cardiomyopathy: comparison of two eras.

OBJECTIVE: To assess the rate and type of genetic diagnosis and clinical outcome of cases of fetal cardiomyopathy (CM) during two eras, in order to examine the impact of advanced genetic testing and improved perinatal management strategies. METHODS: All diagnoses of fetal CM in Alberta, Canada, encountered between 2003 and 2019, were reviewed retrospectively. Genetic, cardiac and non-cardiac diagnoses and clinical outcome were documented. Cases with CM secondary to extracardiac pathology and maternal conditions were excluded. Cases diagnosed in the earlier era of the study period (2003-2012) were compared with those diagnosed in the later era (2013-2019). RESULTS: Thirty-eight cases of fetal CM met the inclusion criteria. Median gestational age (GA) at diagnosis was 22.8 (range, 13.4-37.4) weeks. Associated structural heart disease was present in 39% (15/38) of cases and 24% (9/38) had arrhythmia. Hydrops was identified in 29% (11/38) of cases at presentation, and a further 18% (7/38) developed hydrops later in gestation. Twenty-six percent (10/38) of cases underwent termination of pregnancy and 24% (9/38) had intrauterine death. Of liveborn cases, neonatal death occurred in 16% (3/19), late death occurred in 21% (4/19) and 63% (12/19) were alive at the last follow-up. Excluding cases that had termination of pregnancy and those with a liveborn infant who received planned palliative care, the rate of neonatal survival was higher in the later compared with the earlier era (69% (11/16) vs 45% (5/11)), although the difference was not statistically significant (P = 0.26). A genetic etiology was confirmed in 39% (15/38) of cases and strongly suspected in 24% (9/38). A significantly higher proportion of cases had a confirmed or strongly suspected genetic etiology in the later era compared with in the earlier era (76% (19/25) vs 38% (5/13); P = 0.04). CONCLUSIONS: In the recent era, a higher proportion of fetal CM cases had a confirmed or strongly suspected genetic etiology than reported previously. Based on comparison with older series, modern perinatal management strategies may not have a significant impact on neonatal survival in cases of fetal CM; however, a larger study would be better powered to detect more subtle differences. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal echocardiographic predictors of biventricular circulation in hypoplastic left heart complex.

OBJECTIVES: To determine which echocardiographic features of hypoplastic left heart complex (HLHC) in the fetal period are predictive of biventricular (BV) circulation and to evaluate the long-term outcome of patients with HLHC, including rates of mortality, reintervention and development of further cardiac disease. METHODS: Echocardiograms of fetuses with HLHC obtained at 18-26 weeks and 27-36 weeks' gestation between 2004 and 2017 were included in the analysis. The primary outcome was successful BV circulation (Group 1). Group 2 included patients with single-ventricle palliation, death or transplant. Univariate analysis was performed on data obtained at 18-26 and 27-36 weeks and multivariate logistic regression was performed on data obtained at 27-36 weeks only. RESULTS: Of the 51 included cases, 44 achieved successful BV circulation (Group 1) and seven did not (Group 2). Right-to-left/bidirectional foramen ovale (FO) flow and a higher mitral valve (MV) annulus Z-score were associated with successful BV circulation on both univariate and multivariate analysis. Bidirectional or left-to-right FO flow, left ventricular length (LVL) Z-score of < -2.4 and a MV Z-score of < -4.5 correctly predicted 80% of Group 2 cases. Late follow-up was available for 41 patients. There were two late deaths in Group 2. Thirteen patients in Group 1 required reintervention, 12 developed mitral stenosis and five developed isolated subaortic stenosis. CONCLUSIONS: BV circulation is common in fetuses with HLHC. Higher MV annulus and LVL Z-scores and right to left direction of FO flow are important predictors of BV circulation. Long-term sequelae in those with BV circulation may include mitral and subaortic stenosis. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal features of ductus arteriosus-related branch pulmonary stenosis in fetal pulmonary atresia.

OBJECTIVE: Ductus arteriosus (DA)-related branch pulmonary stenosis (PS), due to ductal tissue migration into the proximal pulmonary artery (PA) ipsilateral to the DA, is common in newborns with pulmonary atresia (PAtr) and contributes significantly to their mortality and morbidity. We sought to define fetal echocardiographic predictors of DA-PS in PAtr. METHODS: This was a study of all neonates diagnosed prenatally with PAtr and a DA-dependent pulmonary circulation, with a DA that joined the underbelly of the arch, who had undergone surgical or catheter intervention in our hospital between 2009 and 2018. The postnatal echocardiograms and clinical records were reviewed to confirm the presence or absence of DA-PS based on the need for angioplasty at initial intervention and/or development of proximal PA stenosis post intervention. Fetal echocardiograms were examined for the features of DA-PS. RESULTS: Of 53 fetuses with PAtr, 34 (64%) had analyzable images, including 20/34 (59%) with and 14/34 (41%) without DA-PS. An inability to visualize the branch PAs in the same plane, largely associated with abnormal DA insertion into the ipsilateral PA (85% of cases), had sensitivity, specificity and positive (PPV) and negative (NPV) predictive values of 75%, 100%, 100% and 74%, respectively, for the prediction of postnatal DA-PS. The mean branch PA posterior bifurcation angle was more obtuse in cases with DA-PS compared to cases without DA-PS (117° ± 17° vs 79° ± 17°, P < 0.001), and an angle of > 100°, the preoperative cut-off observed previously in affected newborns, had a sensitivity, specificity, PPV and NPV of 88%, 79%, 82% and 85%, respectively. The receiver-operating-characteristics curve revealed an angle of ≥ 105° to have a sensitivity and specificity of 88% and 93%, respectively, for prenatal prediction of DA-PS. The presence of one or both features (inability to image in the same plane and the posterior bifurcation angle of ≥ 105°) had a sensitivity, specificity, PPV and NPV of 100%, 93%, 95% and 100%, respectively. CONCLUSION: An inability to visualize the branch PAs in the same plane, associated with abnormal insertion of the DA in most cases, and/or the presence of a posterior PA bifurcation angle of ≥ 105° are predictive features of postnatal DA-PS in fetuses with PAtr. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Population trends in prenatal detection of transposition of great arteries: impact of obstetric screening ultrasound guidelines.

OBJECTIVES: Dextro-transposition of the great arteries (d-TGA) is one of the most common critical neonatal heart defects, with a low detection rate antenatally. We sought to evaluate trends in the prenatal detection of d-TGA with or without ventricular septal defect (VSD) in Alberta over the past 13 years, examining the potential impact of ultrasound guidelines incorporating screening of cardiac outflow tracts, updated in 2009-2010 and in 2013, and factors affecting detection of the condition. METHODS: All fetuses and neonates with d-TGA, with or without VSD, encountered between 2003 and 2015 in the province of Alberta, were identified retrospectively. Clinical records including obstetric ultrasound reports were reviewed. Pregnancy outcome, common referral indications and associated maternal and fetal pathology in affected pregnancies were assessed. RESULTS: From 2003 to 2015, 127 cases with d-TGA were encountered in Alberta, of which 47 (37%) were detected prenatally. Prenatal detection improved over the study period, from 14% in 2003-2010, to 50% in 2011-2013, and to 77% in 2014-2015. Of the 47 fetuses with a prenatal diagnosis of d-TGA, an indication for fetal echocardiography included abnormal or poorly visualized cardiac outflows with normal four-chamber view in 46 (98%). Comorbidities were identified in 12 mothers, only five of which represented an additional reason for fetal echocardiography referral, and four fetuses had extracardiac pathology. CONCLUSION: Substantial improvement in the prenatal detection of d-TGA has been observed in Alberta over the past few years, owing to improved screening of cardiac outflow tracts on routine obstetric ultrasound examination in otherwise healthy pregnancies, and has been temporally associated with updated obstetric ultrasound guidelines suggesting that these contributed to optimized screening of affected pregnancies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Parameters of fetal pulmonary vascular health: baseline trends and response to maternal hyperoxia in the second and third trimesters.

OBJECTIVES: Several parameters, including branch pulmonary artery (PA) diameter and Doppler-derived PA acceleration-to-ejection time ratio (AT/ET), peak late-systolic/early-diastolic reversed flow (PEDRF) and pulsatility index (PI) response to maternal hyperoxia, have been used to investigate fetal pulmonary health. Lower AT/ET, increased PEDRF and lack of PI response to hyperoxia have been observed in fetuses with severe lung hypoplasia and are considered markers of pulmonary vascular resistance. We sought to further define the evolution of PA diameter and Doppler parameters and their response to maternal hyperoxia in healthy fetuses. METHODS: Fifty-four prospectively recruited women with healthy pregnancy underwent fetal echocardiography from 18-36 weeks of gestation. After baseline branch PA diameter and Doppler assessment, oxygen (8-10 L/min) was administered by non-reservoir facemask for 10 min and PA Doppler parameters were reassessed. RESULTS: Branch PA diameters and AT/ET increased linearly with gestational age, while PEDRF increased quadratically (P < 0.001 for all) and PA-PI did not change. In response to maternal hyperoxia, although most fetuses demonstrated a significant decrease in PI for both branch PAs (right PA, P = 0.025; left PA, P = 0.040) ≥ 30 weeks, significant variability was observed in PI response with 31% of cases demonstrating either no response or a slight decrease. No other parameter demonstrated a measurable change in response to maternal hyperoxia. CONCLUSIONS: From the mid-trimester, fetal branch PA diameters and AT/ET increase linearly and PEDRF increases quadratically, whereas PI remains unchanged. Although maternal hyperoxia triggers a significant decrease in PA-PI after 30 weeks, variability in this response may reduce its utility in clinical practice. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Severe left heart obstruction with retrograde arch flow influences fetal cerebral and placental blood flow.

OBJECTIVE: Decreased middle cerebral artery (MCA) pulsatility index (PI) is a marker of fetal brain-sparing in placental insufficiency and it is also found in fetuses with severe congenital heart disease. This study sought to explore the impact of anatomical subtypes in fetal heart disease on MCA-PI and head growth. METHODS: We retrospectively reviewed fetal echocardiograms of pregnancies complicated by fetal hypoplastic left heart syndrome (HLHS; n = 42) with and without anatomic coarctation (n = 28 and n = 10, respectively), isolated severe aortic coarctation (n = 21), D-transposition of the great arteries (TGA; n = 11) and pulmonary outflow tract obstruction without forward flow across the pulmonary valve (POTO; n = 15), comparing observations with gestational age-matched controls (n = 89). No fetus had major extracardiac pathology or aneuploidy. MCA and umbilical artery (UA) PI, the cerebral placental ratio (CPR = MCA-PI/ UA-PI) and neonatal head circumference were obtained and expressed as Z-scores. RESULTS: Lower MCA-PI, higher UA-PI and lower CPR were observed in fetal HLHS and isolated coarctation with reversed arch flow (n = 6) (P < 0.001) but not TGA, POTO or isolated coarctation with antegrade arch flow (n = 15) compared with controls. No difference was found between HLHS with anatomical coarctation and those without; however, MCA-PI correlated positively with neonatal head circumference in HLHS with reversed distal arch flow (r = 0.33, P < 0.05). CONCLUSIONS: Severe left heart obstruction with reversed aortic arch flow is associated with altered fetal cerebral blood flow, and in these conditions, MCA-PI positively correlates with head growth. Anatomical arch obstruction itself may not be a contributing factor to altered MCA flow in fetal HLHS.

Fetal cardiac function in recipient twins undergoing fetoscopic laser ablation of placental anastomoses for Stage IV twin-twin transfusion syndrome.

OBJECTIVE: Cardiac dysfunction is common in the recipient fetus of twin-twin transfusion syndrome (TTTS). In this study, we aimed to document the severity of fetal cardiac dysfunction in Stage IV TTTS (fetal hydrops) and assess evolution of cardiac function longitudinally after fetoscopic laser surgery. METHODS: We reviewed obstetric ultrasound examination data, pre- and postoperative echocardiograms and neonatal outcomes for 22 cases of Stage IV TTTS undergoing fetoscopic laser ablation of placental anastomoses between 1998 and 2011. Myocardial performance index, atrioventricular valve flow patterns, ventricular shortening fraction, ventricular hypertrophy, outflow tract obstruction and venous Doppler waveforms were assessed. RESULTS: Nineteen fetuses (86.4%) had ascites, eight (36.4%) had pleural effusions, nine (40.9%) had a pericardial effusion and 12 (54.5%) had subcutaneous edema at presentation. Preoperatively, cardiac function was grossly abnormal in all. Eight fetuses (36.4%) had functional pulmonary atresia and one (4.5%) had functional aortic atresia. Seventy-seven percent of recipient fetuses survived until birth. Postoperative echocardiographic follow-up (mean, 26 days) showed that indices of fetal cardiac function improved considerably, but never completely normalized. Six of the eight fetuses with functional pulmonary atresia (75.0%), as well as the fetus with functional aortic atresia, survived to birth. In all cases, the functional atresia resolved within 48 h of laser ablation therapy and none had structural valve anomalies at birth. All fetal effusions resolved after the laser. CONCLUSIONS: Fetoscopic laser ablation of placental anastomoses reverses cardiac dysfunction and valvulopathy, even in the most severe cases of TTTS. However, recovery takes longer than in early stage disease.

Changes in fetal cardiac axis between 8 and 15 weeks' gestation.

OBJECTIVES: To document changes in the normal embryonic/fetal cardiac axis in the late first and early second trimesters of pregnancy. METHODS: Images from 188 fetal echocardiograms performed prospectively between 8 and 15 weeks' gestation in 166 healthy pregnancies and in 10 pregnancies with severe fetal heart disease were reviewed. For each echocardiogram, three measurements of the cardiac axis were taken in the axial plane at the level of the four-chamber view. Differences in mean embryonic/fetal cardiac axis at different gestational ages in the healthy pregnancies were compared. RESULTS: The mean ± SD embryonic/fetal cardiac axis was 25.5 ± 11.5° from 8 + 0 to 9 + 6 weeks (Group 1), 40.4 ± 9.2° from 10 + 0 to 11 + 6 weeks (Group 2), 49.2 ± 7.4° from 12 + 0 to 12 + 6 weeks (Group 3), 50.6 ± 5.7° from 13 + 0 to 13 + 6 weeks (Group 4) and 48.6 ± 7.3° from 14 + 0 to 14 + 6 weeks (Group 5). Groups 1 and 2 were significantly different from each other and all other groups (P < 0.05). The results for 22 cases with repeat measurements from 8 + 0 to 11 + 6 and 12 + 0 to 14 + 6 weeks confirmed that the embryonic/fetal cardiac axis increased significantly (P < 0.001). In the cases with severe congenital heart disease, the cardiac axis was > 90th centile in four cases and < 10th centile in two cases. CONCLUSIONS: The embryonic cardiac axis is relatively midline at 8 weeks and levorotates in the late first trimester. By 12 weeks' gestation, the normal leftward fetal cardiac axis is established and remains stable until at least 14 + 6 weeks. Observation of an abnormal cardiac axis in some cases of severe congenital heart disease prior to 15 weeks' gestation may assist in prenatal detection.

Effect of selective fetoscopic laser photocoagulation therapy for twin-twin transfusion syndrome on pulmonary valve pathology in recipient twins.

OBJECTIVE: To investigate the impact of selective fetoscopic laser photocoagulation (SFLP) on pre-existing pulmonary valve pathology in the recipient twin in twin-twin transfusion syndrome (TTTS). METHODS: We evaluated preoperative echocardiograms of all pregnancies with TTTS treated with SFLP at our institution from 2001 to 2009 (n = 76). Sixteen (21%) recipients had an abnormal pulmonary valve (stenosis/dysplasia, insufficiency or functional atresia) before SFLP. Postoperative echocardiograms and medical records from these 16 recipients were reviewed. Changes in pulmonary valve structure and function, and overall cardiac function, were noted after SFLP. RESULTS: The mean gestational age at SFLP was 21 (range, 18.7-24.3) weeks. Seven of sixteen (44%) recipients with abnormal pulmonary valve prior to SFLP survived. Six of the 16 (37.5%) recipient twins had documented absence of persistent pulmonary valve abnormalities at birth or at autopsy. Two (12.5%) of the 16 recipients (2.6% of the original cohort) had persistent pulmonary valve abnormalities at birth, requiring intervention. Systolic and diastolic function improved or normalized after SFLP in all patients undergoing longitudinal follow-up. There was a tendency for a better cardiovascular profile score (best = 10 points) at initial evaluation in pregnancies with survivors compared with those with no survivors (mean (SD): 5.6 (2.2) vs. 6.75 (1.28)), but this was not statistically significant. Severity of cardiac involvement did not predict persistence of valve pathology or survival. CONCLUSIONS: SFLP can improve flow through the pulmonary valve of the recipient twin in TTTS, probably as a consequence of improvements in right ventricular systolic and diastolic function. However, pulmonary valve pathology may persist and require postnatal intervention.

Spectrum of cardiac involvement in neonatal lupus.

'Neonatal' lupus erythematosus (NLE) describes a clinical spectrum of cardiac and non-cardiac abnormalities observed in neonates and foetuses whose mothers have the auto-antibodies anti-SSA/Ro (anti-Ro) and anti-SSB/La (anti-La). Of the cardiac abnormalities, congenital AVB is the most common cardiovascular abnormality found in affected foetuses and infants. Many other cardiovascular manifestations of NLE have been more recently recognized including atrial and ventricular arrhythmias and other conduction abnormalities, myocarditis, cardiomyopathy often with endocardiofibroelastosis and structural heart disease, particularly valvar lesions. In this report, the spectrum of cardiovascular manifestations observed in foetuses and infants with NLE are reviewed and the pathogenesis, diagnosis and clinical outcomes are briefly discussed.

A case of restrictive cardiomyopathy presenting in fetal life with an isolated pericardial effusion.

We describe the evolution during pregnancy of a case of restrictive cardiomyopathy which first presented at 22 weeks' gestation with a large pericardial effusion. Measurements of cardiac function were normal and remained near normal until late in the third trimester, when pulsed and tissue Doppler data suggested impairment in ventricular relaxation. This disease progressed in postnatal life to symptomatic restrictive cardiomyopathy by 2 years of age necessitating cardiac transplant. To our knowledge, this is the first time this unusual association has been reported.

Prenatal diagnosis of primary pulmonary hypoplasia in fraternal twins.

Primary pulmonary hypoplasia is a rare, usually lethal, condition presenting only after birth without other congenital abnormalities. We describe the first case of fraternal twins diagnosed prenatally with primary pulmonary hypoplasia. Both had diffuse hypoplasia of the pulmonary arteries initially identified by fetal echocardiography and confirmed at autopsy following termination. These cases permit examination of the histopathology of this disease in the fetal stage of development.

Extracardiac lesions and chromosomal abnormalities associated with major fetal heart defects: comparison of intrauterine, postnatal and postmortem diagnoses.

OBJECTIVES: The clinical outcome of prenatally diagnosed congenital heart defects (CHD) continues to be affected significantly by associated extracardiac and chromosomal abnormalities. We sought to: determine the frequency and type of major extracardiac abnormalities (with impact on quality of life) and chromosomal abnormalities associated with fetal CHD; and compare the extracardiac abnormalities detected prenatally to the postnatal and autopsy findings in affected fetuses, to find the incidence of extracardiac abnormalities missed on prenatal ultrasound. METHODS: We reviewed the computerized database of the Division of Cardiology of the Hospital for Sick Children in Toronto to identify all cases of major CHD detected prenatally from 1990 to 2002. Medical records, fetal echocardiograms and ultrasound, cytogenetic and autopsy reports were reviewed. The types of CHD detected were grouped into categories and the frequencies of major extracardiac and chromosomal abnormalities in these categories were noted. Prenatal ultrasound findings were compared with those at autopsy or postnatal examination. RESULTS: Of 491 fetuses with major structural CHD, complete data were obtained for 382. Of these, there were 141 (36.9%) with major extracardiac abnormalities at autopsy or postnatal exam, of which 46 had chromosomal abnormalities and 95 did not. In the absence of chromosomal abnormalities, the organ systems most affected were urogenital (12.2%) and gastrointestinal (11.6%). CHDs with the highest incidence of extracardiac abnormalities (>25%) included: heterotaxy, single left ventricle and tricuspid atresia, hypoplastic left heart syndrome and tetralogy of Fallot. Ninety-four of 334 (28.1%) fetuses tested had chromosomal abnormalities. The most common chromosomal abnormalities were trisomies 21 (43.6%), 18 (19.1%) and 13 (9.6%), monosomy X (7.4%) and 22q11.2 deletion (7.4%). Of 289 extracardiac abnormalities from the complete series, 134 (46.4%) were not identified prenatally. Of the missed extracardiac abnormalities, 65 were considered not detectable at prenatal ultrasound, so 23.9% (69/289) of detectable extracardiac abnormalities were missed prenatally. CONCLUSIONS: Major extracardiac and chromosomal abnormalities are common in fetuses with major fetal CHD. Many important associated extracardiac abnormalities may be missed prenatally, which should be taken into consideration in the prenatal counseling for fetal CHD.

Color M-mode propagation velocity, but not its ratio to early diastolic inflow velocity, changes throughout gestation in normal human fetuses.

OBJECTIVES: Color M-mode propagation velocity (Vp) is a measure of diastolic function in adults and, when combined with early diastolic inflow velocity (E), the ratio E/Vp reflects ventricular filling pressure. Early detection of diastolic compromise may benefit fetal patients at risk for developing heart failure. The objectives of this study were to measure values for Vp and inflow peak E in a group of normal fetuses, to analyze age-dependent alterations in these measurements, and to evaluate the interobserver and intraobserver variability of the measurements. METHODS: Thirty-two normal fetuses at between 20 and 35 weeks' gestation underwent echocardiography. Color M-mode Vp was measured from the four-chamber view for the right (RV) and left (LV) ventricles, and mitral and tricuspid inflow velocities were determined by pulsed-wave Doppler ultrasound. The values obtained were compared with previously reported findings in adults. RESULTS: Adequate tracings were obtainable in 23 patients for the RV and 29 for the LV. Mean Vp values for the RV (15.3 +/- 3.2 cm/s) and LV (20.8 +/- 5.6 cm/s) were lower than normal adult values, and Vp values were significantly lower for the RV than the LV (P < 0.001). Applying Bazett's heart rate correction, values for RV (23.4 +/- 4.8 cm/s) and LV (31.9 +/- 8.7 cm/s) remained lower than normal adult values. There was a linear correlation of Vp with gestational age for the RV (R = 0.69, P < 0.001), and the ratio of E/Vp corrected for heart rate for the RV (1.51 +/- 0.26) remained constant throughout gestation. Interobserver bias was high but intraobserver bias low, at 19 and 1.1%, respectively. CONCLUSIONS: Vp is lower in fetal than in adult life. Vp for the RV changes in a manner indicative of improving diastolic function throughout normal gestation, providing insight into the alterations in diastolic function with gestation that contribute to increases in cardiac output. The use of Vp to assess diastolic function disturbance in fetuses is feasible, but high interobserver variability is problematic.