Congenital Heart Disease Fetuses Research Articles

The yield of SNP microarray analysis for fetal ultrasound cardiac abnormalities.

Chromosomal microarray analysis (CMA) has emerged as a critical instrument in prenatal diagnostic procedures, notably in assessing congenital heart diseases (CHD). Nonetheless, current research focuses solely on CHD, overlooking the necessity for thorough comparative investigations encompassing fetuses with varied structural abnormalities or those without apparent structural anomalies. This study sought to assess the relation of single nucleotide polymorphism-based chromosomal microarray analysis (SNP-based CMA) in identifying the underlying causes of fetal cardiac ultrasound abnormalities. A total of 2092 pregnant women who underwent prenatal diagnosis from 2017 to 2022 were included in the study and divided into four groups based on the presence of ultrasound structural abnormalities and the specific type of abnormality. The results of the SNP-Array test conducted on amniotic fluid samples from these groups were analyzed. Findings from the study revealed that the non-isolated CHD group exhibited the highest incidence of aneuploidy, overall chromosomal abnormalities, and trisomy 18, demonstrating statistically significant differences from the other groups (p < 0.001). Regarding the distribution frequency of copy number variation (CNV) segment size, no statistically significant distinctions were observed between the isolated CHD group and the non-isolated CHD group (p > 0.05). The occurrence rates of 22q11.2 and 15q11.2 were also not statistically different between the isolated CHD group and the non-isolated congenital heart defect group (p > 0.05). SNP-based CMA enhances the capacity to detect abnormal CNVs in CHD fetuses, offering valuable insights for diagnosing chromosomal etiology and facilitating genetic counseling. This research contributes to the broader understanding of the utility of SNP-based CMA in the context of fetal cardiac ultrasound abnormalities.

Associations of elevated glucose levels at each time point during OGTT with fetal congenital heart diseases: a cohort study of 72,236 births

BackgroundIt remains unclear how the condition of glucose metabolism during pregnancy affects fetal outcomes. This study aimed to investigate the associations of gestational diabetes mellitus (GDM) and elevated glucose levels at each time point during oral glucose tolerance test (OGTT) with congenital heart disease (CHD) risk in offspring.MethodsWe conducted a retrospective cohort study of mothers with singleton pregnancies of 20 weeks or more registered at Maternal and Child Health Centers in Fujian Province, China. The OGTT results and offspring CHD occurrence were collected. We used logistic regression to analyse the association between elevated blood glucose at each time point during OGTT and CHD.ResultsA total of 71,703 normal and 533 CHD fetuses were included. Compared to the corresponding normal group, women with GDM, elevated blood glucose at different time points in OGTT (0 h ≥ 5.1 mmol/L, 1 h ≥ 10 mmol/L, and 2 h ≥ 8.5 mmol/L) showed an increased risk of CHD in offspring (adjusted OR = 1.41, 1.36, 1.37, and 1.41, all P < 0.05, respectively). Compared to group 1 (normal OGTT 0 h, 1 h and 2 h), the risk of CHD was higher in group 3 (normal OGTT 0 h and abnormal OGTT 1 h or 2 h) and group 4 (abnormal OGTT 0 h, 1 h and 2 h), OR = 1.53 and 2.21, all P < 0.05, respectively. Moreover, we divided participants by advanced maternal age, multipara, assisted reproduction, fetal sex, and others, similar associations were observed in the subgroup analyses.ConclusionElevated blood glucose at different time points during OGTT was associated with CHD in offspring. Fetuses of pregnant women with GDM should be screened for a high risk of CHD.

The Construction of an Intrauterine Diagnosis and Treatment System and Comprehensive Lifecycle Health Service of Congenital Heart Disease: Xinhua Hospital Model

With the growing influence of slow population growth and population aging, China has established the birth policy and issued a series of documents to promote maternal and fetal health and improve the birth rate. With the increase in prevalence of birth defects, timely diagnosis and intervention in utero provide possibilities to reduce unnecessary abortions and offer better prognosis. Congenital heart disease (CHD), as one of the most common congenital birth defects, is the leading cause of mortality in patients aged &lt;5 years, and brings a heavy burden to both the affected families and society. Fetuses with CHD are associated with an increased risk of pregnancy-related complications and premature birth, and children with CHD typically face growth and developmental problems even after the correction of malformation. Therefore, management including diagnosis, treatment, and rehabilitation throughout the fetal period into childhood and even adulthood is essential for children with CHD. Based on the rapid advances in intrauterine and perinatal medicine and an in-depth collaboration among obstetrics and pediatrics, a novel diagnosis and treatment system has been established for the management of CHD in the past 2 decades in Shanghai Xinhua Hospital. This Intrauterine Diagnosis and Treatment System and Comprehensive Lifecycle Health Service of Congenital Heart Disease model provides prenatal diagnosis, intrauterine intervention, delivery room service and neonatal therapies, and postintrauterine rehabilitation for children with CHD. We have developed a four-dimensional spatiotemporal image correlation echocardiography and a three-dimensional cardiac virtual endoscopy system for the intrauterine diagnosis of CHD, dramatically raising the diagnostic utility. Our innovative and independent newborn-intervention technique has effectively reduced the re-intervention rate in patients with pulmonary atresia with intact ventricular septum and critical pulmonary stenosis. In 2018, Xinhua Hospital independently performed the case of fetal aortic valvuloplasty in Asia through a multidepartment collaborative effort. All children treated in this system achieved biventricular circulation and a better long-term postoperative outcome. We also have conducted postoperative rehabilitation therapy to promote the development and health of children with CHD. The practice of Xinhua model has reduced unnecessary abortion of CHD fetuses, reduced the mortality rate associated with critical CHD, and improved the mid- and long-term prognosis in CHD, which is essential to promote the fertility level and children’s health. Furthermore, translational medicine platform and the birth cohort Early Life Plan was constructed to explore the origins of major developmental diseases and establish an early intervention model in CHD. This practice of assessment of the intrauterine system has been expanded to other congenital defects in Xinhua Hospital, and sequential treatment of more than 2,000 cases has been completed to date. Based on practice in intrauterine management of CHD and other diseases, the concept of Intrauterine Pediatrics was proposed as a first to emphasize early prevention and intervention of childhood diseases and promote a comprehensive lifecycle service for children. The development and evolution of this system requires further attention not only from researchers but also from the government and global medical communities.

Polymorphisms in gene UGT1A1 modify the association of prenatal exposure to polycyclic aromatic hydrocarbons with congenital heart diseases risk

Introduction Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for the occurrence of congenital heart diseases (CHDs). Genetic susceptibility to PAHs metabolism may modify the exposure–risk relationship. The role of uridine diphosphoglucuronosyl transferase 1A1 (UGT1A1) genetic polymorphisms for modulating the impacts of prenatal PAHs exposure on the risk of CHDs remains to be discovered. Objective The aim of this study was to investigate whether maternal UGT1A1 genetic polymorphisms are associated with fetal susceptibility to CHDs and to assess whether the risk is modified by maternal PAHs exposure. Methods Maternal urinary biomarker of PAHs exposure was determined in 357 pregnant women with CHDs fetuses and 270 controls (pregnant women carrying fetuses without major congenital malformations). Urinary 1-hydroxypyrene-glucuronide (1-OHPG) concentration, a sensitive biomarker for PAHs exposure, was measured using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Maternal single nucleotide polymorphisms (SNPs) in UGT1A1, including rs3755319, rs887829, rs4148323, rs6742078, and rs6717546, were genotyped using an improved multiplex ligation detection reaction (iMLDR) technique. Unconditional logistic regression was performed to determine the impacts of UGT1A1 polymorphisms on the risks of CHDs and their subtypes. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene–gene and gene–PAHs exposure interactions. Results None of the selected UGT1A1 polymorphisms was independently associated with the risk of CHDs. The interaction between SNP rs4148323 and PAHs exposure was observed to be associated with CHDs (p< .05). Pregnant women with high-level PAHs exposure and rs4148323 had an increased risk of carrying CHDs fetuses (GA-AA vs. GG: aOR = 2.00, 95% CI = 1.06–3.79). Moreover, the joint effect of rs4148323 and PAHs exposure was found to be significantly associated with risks of septal defects, conotruncal heart defects, and right-sided obstructive malformations. Conclusions Maternal genetic variations of UGT1A1 rs4148323 may modify the association between prenatal PAHs exposure and CHDs risk. This finding needs to be further confirmed in a larger-scale study.

Associated factors for prenatally diagnosed fetal congenital heart diseases

ObjectiveCurrent studies have suggested that fetal congenital heart diseases (CHDs) are caused by various factors. However, few data in this field is available in China.This study aimed to detect associated factors of prenatally diagnosed fetal CHD in a large sample in China.Study designPregnant women who underwent fetal echocardiography were recruited in our hospital between May 2018 and September 2019. The maternal sociodemographic and lifestyle characteristics and some fetal factors were obtained. We used forward stepwise logistic regression analysis to assess risk of fetal CHD associated with various factors.ResultsA total of 5024 subjects were enrolled, of whom 875 had CHD fetuses. Among the fetal CHD group (N = 875), critical CHDs account for 27%, of which Tetralogy of Fallot is the most (7.1%), followed by coarctation of aorta (4.0%), double-outlet right ventricle (2.9%). The forward stepwise logistic regression models revealed that history of spontaneous abortion (OR = 1.59, 95% CI 1.33–1.91, P = 0.000), upper respiratory tract infection during early pregnancy (OR = 1.30, 95% CI 1.04–1.62, P = 0.020), mental stress during early pregnancy (OR = 2.37, 95% CI 1.15–4.91, P = 0.020), single umbilical artery (OR = 2.30, 95% CI 1.18–4.51, P = 0.015), and paternal smoking (OR = 1.21, 95% CI 1.02–1.44, P = 0.027) are positively associated with an increased risk of fetal CHD.ConclusionWe identified several factors positively associated with fetal CHD. These findings suggest that it is important to strengthen healthcare and prenatal counseling for women with these factors.

Abstract 15837: Decreased Placental Blood Flow in Fetuses With Congenital Heart Disease is Associated With Placental Vascular Abnormalities and Impaired Fetal Growth

Introduction: Studies suggest the placenta is abnormal in fetuses with congenital heart disease (CHD), possibly due to shared abnormal vascular developmental pathways. Umbilical venous volume flow (UVVF) is a validated Doppler-derived noninvasive imaging method to assess blood flow from placenta to fetus. We previously demonstrated that mid-gestational UVVF is decreased in fetuses with CHD compared to controls. We hypothesize that decreased UVVF in fetuses with CHD is associated with placental vascular abnormalities as well as impaired fetal growth. Methods: Pregnant women carrying fetuses with CHD (n=38; n=29 single ventricle (SV); n=8 TOF, n=1 d-TGA) or without (n=38) were enrolled in a prospective case-control study. UVVF and combined cardiac output (CCO) were measured during second trimester fetal echocardiograms (echo). Postnatal placentas were analyzed and assigned a placental abnormality severity score (PASS) based on the degree of lesions associated with fetal vascular malperfusion (FVM) and chronic inflammation (CI). Biometrics were collected for all newborns. T-tests or Fisher’s Exact tests were performed to assess statistical significance. Results: Gestational age (GA) at time of fetal echo was slightly greater for the CHD group (Table). All CHD fetuses as well as subgroup analysis of SV only had decreased UVVF indexed to fetal weight (UVVF/Wt) and to CCO (UVVF/CCO). Placental PASS analysis demonstrated higher grade FVM and CI lesions in fetuses with CHD. Fetuses with CHD were born earlier and had decreased birth weight z-scores compared to controls. Conclusions: Fetuses with CHD demonstrate decreased placental blood flow in utero, higher grade placental lesions associated with FVM and CI, and decreased birth weight. UVVF reflects characteristics of abnormal placental pathology and may be a useful marker of placental malperfusion in fetuses with CHD. Future study looking at association of UVVF and clinical outcomes is warranted.

Fetal heart foramen ovale area by three-dimensional ultrasound using stic in the rendering mode: reference range and applicability in congenital heart diseases.

To determine reference values for the foramen ovale (FO) area of fetal hearts by three-dimensional (3D) ultrasound using spatio-temporal image correlation (STIC) method in the rendering mode, as well as applicability in fetuses with congenital heart disease (CHD). A retrospective and prospective study was performed of 242 normal fetuses and 36 fetuses with CHD between 20 and 33 + 6 weeks of gestation. The FO area was determined in the four-chamber view with manual delineation. To determine the reference curve of the FO area as a function of gestational age (GA), a linear regression model was utilized with an adjusted coefficient of determination (R2). For intra- and interobserver reproducibility calculations, the concordance correlation coefficient (CCC) was used. The mean ± standard deviation (SD) of the FO measurement area was 21.2 ± 1.8 and 48.1 ± 1.9 mm2 at 20 and 33 weeks' gestation, respectively. A linear correlation was observed between the FO area and GA (1.924*GA - 17.95; R2 = 0.91). Good intra- (CCC = 0.97) and interobserver (CCC = 0.94) agreement was observed for the FO area measurement. The mean difference in FO area between normal and CHD fetuses was - 14.4 mm2 (p < 0.001). Reference values for the FO area of fetal hearts were determined by 3D ultrasound using STIC in the rendering mode. This method showed good intra- and interobserver reproducibility and could be used to assess different CHD types.

Alterations in cardiac output in fetuses with congenital heart disease.

Fetuses with severe congenital heart disease (CHD) have altered blood flow patterns. Prior work to assess fetal combined cardiac output (CCO) is limited by sample size and lack of longitudinal gestational data. Our aim was to evaluate CCO in CHD fetuses to determine whether the presence of single ventricle (SV) physiology or aortic obstruction impacts fetal blood flow and cardiovascular hemodynamics. Prospective study including singleton fetuses with CHD (n=141) and controls (n=118) who underwent a mid- and late-gestation fetal echocardiogram. Ventricular cardiac output was calculated using the standard computation. Combined cardiac output was derived as the sum of the right and left cardiac outputs and indexed to estimated fetal weight. Fetuses with two ventricle (2V) CHD had significantly higher CCO compared to controls and SV CHD fetuses. Fetuses with SV-CHD had similar CCO compared to controls. Fetuses with 2V-CHD and aortic obstruction had significantly higher CCO than fetuses with SV-CHD and aortic obstruction. Our findings suggest that the SV can compensate and increase CCO despite the lack of a second functioning ventricle, however, the degree of compensation may be insufficient to support the increased blood flow needed to overcome the hemodynamic and physiologic alternations seen with severe CHD.

Prenatal Detection of Congenital Heart Diseases Using Echocardiography: 12-Year Results of an Improving Program With 9782 Cases.

BackgroundA provincial program combining the effect of a government investment in prenatal screening and a specialized cardiac center was introduced in 2004, to improve prenatal diagnosis by echocardiography for congenital heart diseases (CHDs) in the Guangdong Registry of Congenital Heart Disease, China.ObjectivesTo evaluate the effects of this program on the prenatal diagnosis rate (PDR) by echocardiography and termination of pregnancy (TOP).MethodsA retrospective study from 2004-2015 included 9782 fetuses and infants diagnosed with CHDs. The PDR was calculated for major and minor CHDs during pre-, mid- and post-program time-intervals. Multivariable logistic regression was utilized to analyze the associations between program implementation and the timing of CHD diagnosis (prenatal vs. postnatal) by different hospital levels. The rate for TOP were also evaluated.ResultsThe PDR increased by 44% for major CHDs in the post-program interval relative to the pre-program interval. The three most frequently diagnosed subtypes prenatally were hypoplastic left heart syndrome (84%), double outlet right ventricle (83%) and severe pulmonary stenosis (82%). Participants with a high school education experienced a greater increase in PDR than those without a high school education. The odds for a prenatal vs. a postnatal diagnosis for major CHD were greater after introduction of the program than before (adjusted odd ratio= 20.95, 95% CI:2.47, 178.06 in secondary hospitals; and adjusted odd ratio=11.65, 95% CI:6.52, 20.81 in tertiary hospitals). The TOP rate decreased from 52.3% pre-program to 19.6% post-program among minor CHD fetuses with a prenatal diagnosis (P for trend =0.041). A lower proportion of TOP were attributed to minor CHDs after the program.ConclusionsThe program combining the advantages of government investment and a specialized cardiac center appeared to increase the PDR by echocardiography for CHDs in an unselected population. The TOP rate among minor cases with prenatal diagnosis declined significantly after implementation of the program.

Brain Oxygen Perfusion and Oxidative Stress Biomarkers in Fetuses with Congenital Heart Disease-A Retrospective, Case-Control Pilot Study.

Fetuses with congenital heart disease (CHD) have circulatory changes that may lead to predictable blood flow disturbances that may affect normal brain development. Hypoxemia and hypoperfusion may alter the redox balance leading to oxidative stress (OS), that can be assessed measuring stable end-products. OS biomarkers (OSB) were measured in amniotic fluid in fetuses with (n = 41) and without CHD (n = 44) and analyzed according to aortic flow, expected cyanosis after birth, and a CHD classification derived from this. Birth head circumference (HC) was used as a neurodevelopment biomarker. CHD fetuses had higher levels of ortho-Tyrosine (o-Tyr) than controls (p = 0.0003). There were no differences in o-Tyr levels considering aortic flow obstruction (p = 0.617). Fetuses with expected extreme cyanosis presented the highest levels of o-Tyr (p = 0.003). Among groups of CHD, fetuses without aortic obstruction and extreme cyanosis had the highest levels of o-Tyr (p = 0.005). CHD patients had lower HC than controls (p = 0.023), without correlation with OSB. Patients with HC < 10th percentile, presented high levels of o-Tyr (p = 0.024). Fetuses with CHD showed increased OSB and lower HC when compared to controls, especially those with expected extreme cyanosis. Our results suggest that increased levels of OSB are more influenced by the effect of low oxygenation than by aortic flow obstruction. Future studies with larger sample size are needed to further investigate the role of OSB as an early predictor of neurodevelopmental problems in CHD survivors.

Epidemiological Aspects, Prenatal Screening and Diagnosis of Congenital Heart Defects in Beijing.

Background: In China, congenital heart disease (CHD) is the most common birth defect type, with approximately 13,000 new cases annually. This study aimed to investigate high-risk factors, prenatal screening and prenatal diagnosis as a basis for clinical decisions.Methods: All CHD cases identified from 2018 to 2020 were obtained from the Beijing city birth defect surveillance system and prenatal diagnosis institutions. The prenatal CHD diagnosis was confirmed by fetal echocardiography and amniotic fluid or cord blood genetic examination. Chi-square, odds ratio (OR), 95% confidence interval (CI), and univariate and multivariate logistic analyses were used to explore the high-risk factors, prenatal screening and prenatal diagnosis of CHD. Results: In total, 6,786/594,860 fetuses with CHD were diagnosed by prenatal echocardiography. The average incidence of CHD was 11.4 per 1,000 births, with an increase of 30.7 per 1,000 births from 2018 to 2020 (P < 0.05); the average incidence of complex CHD (CCHD) was 2.02 per 1,000 births, with no significant change from 2018 to 2020 (P > 0.05). Women age ≥35 years (OR 1.06, 95% CI 0.77–1.46) was at higher risk of having babies with CHD than women aged 21–34 years. Overall, CHD incidence increased with maternal age (OR1.03, 95% CI 1.02–1.03). Additionally, women who had a non-local household registration (OR 1.16, 95% CI 1.10–1.22) or had diabetes mellitus (DM) (OR 1.16, 95% CI 0.96–1.25) were at higher risk of CHD. As an independent factor, CCHD was related to maternal age, DM, fetal gender, and maternal education level (all P < 0.05). The prenatal ultrasound screening detection rate of CCHD was 97.59%, which was far higher than that of total CHD (51.67%) (P < 0.001). The prenatal ultrasound diagnosis rate of CCHD was higher than that of simple CHD (P < 0.001), but the coincidence rate in the ultrasound diagnosis of CCHD was lower than that of simple CHD (P < 0.001). Prenatal genetic testing revealed chromosomal abnormalities in 25.62% (279/1089) of CHD cases with indications for a prenatal diagnosis.Conclusions: Maternal age, household registration and DM were related to CHD occurrence. Prenatal ultrasound screening is a highly effective method for CCHD diagnosis, and CHD fetuses should be closely evaluated to exclude chromosomal abnormalities.

Three-Dimensional Volumetric Magnetic Resonance Imaging Detects Early Alterations of the Brain Growth in Fetuses With Congenital Heart Disease.

Several published studies have shown alterations of brain development in third-trimester fetuses with congenital heart disease (CHD). However, little is known about the timing and pattern of altered brain development in fetuses with CHD. To investigate the changes in the volume of intracranial structures in fetuses with CHD by three-dimensional (3D) volumetric magnetic resonance imaging (MRI) in the earlier stages of pregnancy (median gestational age [GA], 26 weeks). Retrospective. Forty women carrying a fetus with CHD (including 20 fetuses with GA <26 weeks) and 120 pregnant women carrying a healthy fetus (including 50 fetuses with GA <26 weeks). Two-dimensional single-shot turbo spin echo sequence at 1.5-T. Three-dimensional volumetric parameters from slice-to-volume registered images, including cortical gray matter volume (GMV), subcortical brain tissue volume (SBV), intracranial cavity volume (ICV), lateral ventricles volume (VV), cerebellum, brainstem, and extra-cerebrospinal fluid (e-CSF) were quantified by manual segmentation from one primary and two secondary observers. Volumes were presented graphically with quadratic curve fitting. Scatterplots were produced mapping volumes against GA in normal and CHD fetuses. For GA <26 weeks, Z scores were calculated and Student's t-tests were conducted to compare volumes between the normal and CHD fetuses. In fetuses with CHD GMV, SBV, cerebellum, and brainstem were significantly reduced (all P < 0.05) in early stages of pregnancy (GA <26 weeks), with differences becoming progressively greater with increasing GA. Compared with normal fetuses, e-CSF, e-CSF to ICV ratio, and VV were higher in fetuses with CHD (all P < 0.05). However, ICV volume and the GMV to SBV ratio were not significantly reduced in the CHD group (P=0.94 and P=0.13, respectively) during the middle gestation (GA <26 weeks). There appear to be alterations of brain development trajectory in CHD fetuses that can be detected by 3D volumetric MRI in the earlier stages of pregnancy. 4 TECHNICAL EFFICACY: Stage 3.

Noninherited Factors in Fetal Congenital Heart Diseases Based on Bayesian Network: A Large Multicenter Study

Background: Current studies have confirmed that fetal congenital heart diseases (CHDs) are caused by various factors. However, the quantitative risk of CHD is not clear given the combined effects of multiple factors. Objective: This cross-sectional study aimed to detect associated factors of fetal CHD using a Bayesian network in a large sample and quantitatively analyze relative risk ratios (RRs). Methods: Pregnant women who underwent fetal echocardiography (N = 16,086 including 3,312 with CHD fetuses) were analyzed. Twenty-six maternal and fetal factors were obtained. A Bayesian network is constructed based on all variables through structural learning and parameter learning methods to find the environmental factors that directly and indirectly associated with outcome, and the probability of fetal CHD in the two groups is predicted through a junction tree reasoning algorithm, so as to obtain RR for fetal CHD under different exposure factor combinations. Taking into account the effect of gestational week on the accuracy of model prediction, we conducted sensitivity analysis on gestational week groups. Results: The single-factor analysis showed that the RRs for the numbers of births, spontaneous abortions, and parental smoking were 1.50, 1.38, and 1.11 (P < 0.001), respectively. The risk gradually increased with the synergistic effect of ranging from one to more environmental factors above. The risk was higher among subjects with five synergistic factors, including the number of births, upper respiratory tract infection during early pregnancy, anemia, and mental stress as well as a history of spontaneous abortions or parental smoking, than in those with less than 5 factors (RR = 2.62 or 2.28, P < 0.001). This result was consistent across the participants grouped by GWs. Conclusion: We identified six factors that were directly associated with fetal CHD. A higher number of these factors led to a higher risk of CHD. These findings suggest that it is important to strengthen healthcare and prenatal counseling for women with these factors.

Fetal Cerebral Oxygenation Is Impaired in Congenital Heart Disease and Shows Variable Response to Maternal Hyperoxia.

BackgroundImpairments in fetal oxygen delivery have been implicated in brain dysmaturation seen in congenital heart disease (CHD), suggesting a role for in utero transplacental oxygen therapy. We applied a novel imaging tool to quantify fetal cerebral oxygenation by measuring T2* decay. We compared T2* in fetuses with CHD with controls with a focus on cardiovascular physiologies (transposition or left‐sided obstruction) and described the effect of brief administration of maternal hyperoxia on T2* decay.Methods and ResultsThis is a prospective study performed on pregnant mothers with a prenatal diagnosis of CHD compared with controls in the third trimester. Participants underwent a fetal brain magnetic resonance imaging scan including a T2* sequence before and after maternal hyperoxia. Comparisons were made between control and CHD fetuses including subgroup analyses by cardiac physiology. Forty‐four mothers (CHD=24, control=20) participated. Fetuses with CHD had lower total brain volume (238.2 mm3, 95% CI, 224.6–251.9) compared with controls (262.4 mm3, 95% CI, 245.0–279.8, P=0.04). T2* decay time was faster in CHD compared with controls (beta=−14.4, 95% CI, −23.3 to −5.6, P=0.002). The magnitude of change in T2* with maternal hyperoxia was higher in fetuses with transposition compared with controls (increase of 8.4 ms, 95% CI, 0.5–14.3, P=0.01), though between‐subject variability was noted.ConclusionsCerebral tissue oxygenation is lower in fetuses with complex CHD. There was variability in the response to maternal hyperoxia by CHD subgroup that can be tested in future larger studies. Cardiovascular physiology is critical when designing neuroprotective clinical trials in the fetus with CHD.

Can we Improve the Perinatal Outcomes and Early Postnatal Survival of Fetuses with Congenital Heart Disease by Initiating Specialized Prenatal Consultation Service

Background: Requirements of specialized prenatal consultation after prenatal diagnosis of Congenital Heart Disease (CHD) is increasing, but its impact is not clear. This study was to introduce such a specialized prenatal consultation service and assess its impact on outcomes of CHD fetuses. Methods: We initiated specialized prenatal consultation in a referral tertiary cardiac center in southern China in 2013. A multidisciplinary team serves as consultants in this service and is especially responsible by two pediatric cardiologists in regular outpatient clinics. We included CHD fetuses diagnosed from 2011 to 2015 consecutively. They were divided into before (2011-2013) and after (2014-2015) specialized prenatal consultation groups and their perinatal outcomes, delivery location and early postnatal survival were compared. Risk factors for termination were also assessed. Results: Totally, 1032 CHD fetuses were included and 533 accepted specialized prenatal consultation. After initiation of specialized prenatal consultation, the live birth rate significantly improved (OR=1.59, 95% CI: 1.10-2.29) and termination rate significantly reduced (OR=0.63, 95% CI: 0.44-0.91) in single CHD fetuses. No significant change in delivery location and postnatal survival of CHD fetuses were observed after specialized prenatal consultation. Referrals from district hospitals, along with multiple-lesion CHD, critical CHDs, gestational age<28 weeks at prenatal diagnosis were risk factors for termination. Conclusion: Specialized prenatal consultation can improve the perinatal outcomes in single CHD fetuses. Education for district hospitals of standardizing counseling, especially for minor CHD fetuses and timely transferring of mothers with critical CHDs/multiple CHDs fetus is crucial to improve the outcomes of CHD fetuses further.

Abstract 17283: The Impact of Fetal Congenital Heart Disease on In Vivo Regional Brainstem Development

Introduction: Brain injury and delayed brain development have been reported in fetuses with congenital heart disease (CHD). While reduced volumes of fetal brain structures have been discovered, the shape alternations of the brainstem affected by CHD were not fully investigated. Hypothesis: We assessed the hypothesis that the morphology of the brainstem in CHD fetuses was altered when compared to healthy controls. Methods: A total of 146 pregnant women were recruited for this longitudinal observational study (99 controls and 47 CHD; median gestational age (GA) and range: 33.4 [24.4-39.1] weeks), in which 207 MRI scans were performed. Single shot fast spin echo T2-weighted images were acquired on a 1.5T GE MRI scanner. Anatomical landmarks of brainstem were manually identified on 1 mm 3 isotropic 3D reconstructed images using RView software. Anterior-posterior and transverse diameters of mesencephalon, pons, and medullary were determined based on 12 landmarks on the midsagittal and coronal planes correspondingly. The inter-landmark distances and 2D areas enclosed by landmarks on the midsagittal plane of the two groups were analyzed using generalized estimating equations, adjusting for GA and fetal gender. Results: Results indicated lower regional anterior-posterior diameters of the pons in CHD fetuses [landmarks 2-3, 2-6, 3-4, and 4-6 ( p-values &lt;0.05)]. The 2D areas enclosed by landmarks on the midsagittal plane were overall smaller in CHD fetuses (control: 183±10 mm 2 ; CHD: 175±10 mm 2 ; p =0.016). No differences in transverse diameters were observed between control and CHD fetuses on the three coronal planes. All measured diameters and areas were significantly increased with advancing GA ( p-values &lt;0.05), while no gender differences were detected. Conclusions: We report for the first time impaired regional growth of the pons in fetuses with CHD. The pons may play a role in altered emerging cerebral-cerebellar structure and functional connections in fetal CHD.

Abstract 17061: Impact of Maternal Anxiety on In Vivo Placental Development in Fetuses With Congenital Heart Disease

Introduction: Studies have shown that maternal stress and anxiety during pregnancy have been associated with a higher incidence of preterm birth and low birth weight. However, the relationship between prenatal maternal mental distress and placental development in fetuses with congenital heart disease (CHD) is unknown. Hypothesis: We tested the hypothesis that elevated maternal anxiety is associated with altered placental morphology in fetuses with CHD. Methods: A total of 141 pregnant women were recruited prospectively (control: 91; two-ventricle/2V CHD: 29; single-ventricle/SV CHD: 21), in which 228 fetal MR scans were performed (gestational age: 31.8±4.5 weeks). Single shot fast spin echo T2-weighted images were acquired on a 1.5 Tesla GE MRI scanner. Placenta tissue was manually segmented, and slice-to-volume registration was used for motion correction and 3D reconstruction. Six placental features were calculated: volume, thickness, elongation, surface area, mean diameter, and umbilical cord centricity. We completed the Spielberger State (SSAI) and Trait (SSAI) Anxiety Inventory at each study visit. Linear mixed models were utilized to analyze the placental features predicted by maternal anxiety. Results: Placental volume, surface area, and mean diameter were decreased with elevated SSAI in 2V CHD fetuses, while volume and cord centricity were increased with higher SSAI in SV CHD fetuses. Lower cord centricity was associated with elevated STAI in 2V CHD fetuses, and elongation was positively associated with STAI in SV CHD fetuses. There were no associations between anxiety measures and placental features in control fetuses. Conclusions: We report for the first time that elevated prenatal maternal anxiety is associated with altered in vivo placental structures in pregnancies complicated by fetal CHD. Our data suggest that disturbances in placental structure vary based on the type of fetal CHD (SV vs. 2V) in the setting of elevated prenatal maternal anxiety.

Mid-gestational fetal placental blood flow is diminished in the fetus with congenital heart disease.

Data suggest fetuses with congenital heart disease (CHD) have placental abnormalities. Their abnormal placental vasculature may affect fetal placental blood flow, which has not previously been explored. We performed a retrospective cross-sectional study comparing umbilical venous volume flow (UVVF) of single ventricle, D-transposition of the great arteries, and tetralogy of Fallot fetuses with fetuses without CHD. UVVF and combined cardiac output (CCO) were calculated from fetal echocardiography and compared using t tests, χ2 and Fisher's exact tests. Mean gestational age and fetal weight were greater in CHD fetuses (26.5 weeks, 1119.4 g; n = 81, P < .001) compared to controls (23.1 weeks, 675 g; n = 170, P < .001). UVVF/fetal weight was nevertheless decreased among cases (99.8 vs 115.3 mL/min/kg, P < .001). Subgroup analysis of 20- to 25-week fetuses demonstrated no significant differences in case and control baseline characteristics. In CHD fetuses (n = 31) compared to controls (n = 144), absolute UVVF (50.8 vs 62.1 mL/min, P = .006), and UVVF/fetal weight (98.8 vs 118.5 mL/min/kg, P < .001) were decreased. Findings were similar in single ventricle (n = 24) and hypoplastic left heart syndrome (n = 14). Mid-gestational placental blood flow in CHD fetuses is decreased compared to controls. Further study is needed to explore the relationship between UVVF and placental pathology, and impact on outcomes.

Positive Rate of Noninvasive Prenatal Screening for Pregnancies with Fetal Congenital Heart Disease and Its Impact on Pregnancy Outcome

Abstract Objective: To evaluate the clinical utility of noninvasive prenatal screening (NIPS) for fetuses with congenital heart disease (CHD) and impact of NIPS results on pregnancy outcome. Methods: This was a retrospective study of pregnant women with fetuses diagnosed with CHDs by sonographic examination, who willing to underwent NIPS as a side-test for fetal aneuploidies. From August 2016 to October 2017, in the sonographic examination center of Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. NIPS was offered to 117 women who carried fetuses with CHD diagnosed by fetal ultrasound (mean gestational age = 24 weeks). The pregnancy outcomes were followed-up. Results: NIPS positive rate in our pregnancies with CHD fetuses’ cohort is 11.1% (13/117), and the positive predictive value for aneuploidies is 85.7% (6/7). In the NIPS positive group (n = 13), all pregnancies terminated, 76.9% (10/13) of those decisions were made on ultrasound finding alone. In the NIPS negative group (n = 104), 2 lost follow-up, 79 pregnancies terminated, among which 77.2% (61/79) of the decision was made by ultrasound results alone. Twenty-three pregnancies continued and 78.3% of those fetuses carried single type CHD. In terminated pregnancies that did not considered NIPS results (71/115), 73.2% (52/71) of those carried fetuses with two or more types of CHDs. Conclusion: NIPS can detect common aneuploidy associated with CHD with high positive predictive value and screening yield. The NIPS result played certain meaningful roles in determining pregnancy outcomes, particularly for fetus with simplex CHD; yet the parents’ decision of pregnancy was mainly made based on ultrasound findings.

Discussion

Discussion