Early Clinical Outcomes in Infants with Prenatally Diagnosed Perimembranous and Muscular Ventricular Septal Defects (VSDs).

Isolated ventricular septal defect (VSD) is often associated with good clinical outcomes. However, infants prenatally diagnosed with VSD are often recommended for delivery at tertiary care centers. The aim of our study was to determine the odds of neonatal intensive care unit (NICU) admission in infants with persistent isolated VSD and complicated VSD, where an infant is affected by VSD and other genetic/structural abnormalities. We performed a retrospective cohort study, with data collected from a single academic institution from June 2018 to March 2023. Individuals with prenatally diagnosed VSD, in the absence of any other heart defects, were included in this study. The primary outcome was admission to the NICU. Multivariable logistic regression was used to assess associations. The association between persistence of VSD and NICU admission was adjusted for maternal age, fetal genetic abnormalities, fetal extracardiac abnormalities, and gestational age at the time of delivery. The association between complicated VSD and NICU admission was adjusted for maternal age and gestational age of the infant at the time of delivery. The odds of NICU admission were similar in infants with persistent isolated VSD and VSD that closed in utero (adjusted OR 1.31, 95% CI 0.30-5.61). However, infants with complicated VSD were at increased risk of NICU admission (adjusted OR 15.52, 95% CI 2.90-82.92). The risk of NICU admission was only increased in infants whose VSD was complicated by another genetic/major structural abnormalities. Therefore, women whose infants are prenatally diagnosed with VSD alone may not require delivery at tertiary care centers.

The value of detailed first-trimester ultrasound in the era of noninvasive prenatal testing.

BACKGROUND: In 2020, the American College of Obstetricians and Gynecologists recommended noninvasive prenatal testing be offered to all patients. However, current societal guidelines in the United States do not universally recommend a detailed first-trimester ultrasound. OBJECTIVE: This study aimed to determine the additional findings identified through first-trimester ultrasound that would have otherwise been missed if noninvasive prenatal testing was used alone as a first-trimester screening method. STUDY DESIGN: This was a retrospective cohort study involving 2158 pregnant patients and 2216 fetuses that were seen at a single medical center between January 1, 2020, and December 31, 2022. All those included underwent both noninvasive prenatal testing and detailed first-trimester ultrasound between 11.0 and 13.6 weeks of gestation. Noninvasive prenatal testing results were categorized as low risk or high risk, and first-trimester ultrasound results were categorized as normal or abnormal. Abnormal first-trimester ultrasounds were further classified as first-trimester screening markers (increased nuchal translucency, absent nasal bone, tricuspid regurgitation, and ductus venosus reverse a-wave) or structural defects (the cranium, neck, heart, thorax, abdominal wall, stomach, kidneys, bladder, spine, and extremities). Descriptive statistics were used to report our findings. RESULTS: Of 2216 fetuses, 65 (3.0%) had a high-risk noninvasive prenatal testing result, whereas 2151 (97.0%) had a low-risk noninvasive prenatal testing result. Of those with a low-risk noninvasive prenatal testing result, 2035 (94.6%) had a normal first-trimester ultrasound, whereas 116 (5.4%) had at least 1 abnormal finding on first-trimester ultrasound. The most common screening marker detected within the low-risk noninvasive prenatal testing group was absent nasal bone (52/2151 [2.4%]), followed by reversed a-wave of the ductus venosus (30/2151 [1.4%]). The most common structural defect in this group was cardiac abnormality (15/2151 [0.7%]). Overall, 181 fetuses were identified as having "abnormal screening" through either a high-risk noninvasive prenatal testing result (n=65) or through a low-risk noninvasive prenatal testing result but abnormal first-trimester ultrasound (n=116). In summary, the incorporation of first-trimester ultrasound screening identified 116 additional fetuses (5.4%) that required further follow-up and surveillance than noninvasive prenatal testing alone would have identified. CONCLUSION: Detailed first-trimester ultrasound identified more fetuses with a potential abnormality than noninvasive prenatal testing alone. Therefore, first-trimester ultrasound remains a valuable screening method that should be used in combination with noninvasive prenatal testing.

Genome Editing and Myocardial Development.

Congenital heart disease (CHD) has a strong genetic etiology, making it a likely candidate for therapeutic intervention using genetic editing. Complex genetics involving an orchestrated series of genetic events and over 400 genes are responsible for myocardial development. Cooperation is required from a vast series of genetic networks, and mutations in such can lead to CHD and cardiovascular abnormalities, affecting up to 1% of all live births. Genome editing technologies are becoming better studied and with time and improved logistics, CHD could be a prime therapeutic target. Syndromic, nonsyndromic, and cases of familial inheritance all involve identifiable causative mutations and thus have the potential for genome editing therapy. Mouse models are well-suited to study and predict clinical outcome. This review summarizes the anatomical and genetic timeline of myocardial development in both mice and humans, the potential of gene editing in typical CHD categories, as well as the use of mice thus far in reproducing models of human CHD and correcting the mutations that create them.

Topography of the Heart: Mapping the Fetal Heart Through SlowflowHD.

SlowflowHD is a Doppler Ultrasound modality that is typically geared toward visualization of small-size vessels and low velocity blood flow. In this commentary, we emphasize the importance of implementing the use of SlowflowHD as an adjunct to traditional Doppler modalities in the echocardiography screening in both the first and second trimester. This modality carries many characteristics that allow it to overcome the limitations of our current ultrasound modalities and facilitate mapping of the entirety of the fetal heart. The clinical implications are significant in regard to earlier acquisition of diagnostic information to guide decision-making and patient counseling.

The impact of trimester of COVID-19 infection on pregnancy outcomes after recovery.

OBJECTIVES: Many physiological adaptations occur during pregnancy. It is not currently known how timing of COVID-19 infection impacts pregnancy. We hypothesize that maternal and neonatal outcomes are different if COVID-19 infection occurs in different trimesters of pregnancy. METHODS: This retrospective cohort study was conducted from 3/2020 to 6/2022. Pregnant patients with a positive COVID-19 infection more than 10 days before delivery (COVID-recovered) were identified and grouped by trimester of infection. Demographics and maternal, obstetric, and neonatal outcomes were analyzed. ANOVA, Wilcoxon rank-sum test, Pearson's chi-squared test, and Fisher's exact test were used to compare continuous and categorical data. RESULTS: A total of 298 COVID-recovered pregnant patients were identified. Of those, 48 (16 %) were infected in the 1st trimester, 123 (41 %) in the 2nd, and 127 (43 %) in the 3rd. There were no significant demographic differences between the study groups. Vaccination status was similar. Hospital admission rate and the need for oxygen therapy while infected were significantly higher in patients with 2nd or 3rd trimester infection (18 % & 20 % vs. 2 % and 13 % & 14 % vs. 0 %, respectively). Rates of preterm birth (PTB) and extreme PTB were higher in the 1st trimester infection group. Infants born to mothers infected in the 2nd trimester had more neonatal sepsis workups (22 % vs. 12 % & 7 %). Other outcomes were similar between groups. CONCLUSIONS: First trimester COVID-recovered patients were more likely to have a preterm birth despite having lower rates of hospital admission and oxygen supplementation while infected than patients who recovered from a 2nd or 3rd trimester infection.

The Impact of Neighborhood Socioeconomic Status, Race and Ethnicity, and Language on Prenatal Diagnosis of CHD.

Congenital heart disease (CHD) is the most prevalent birth defect. This study aimed to assess whether prenatal diagnosis (PD) of CHD and time of the diagnosis are associated with maternal race, ethnicity, neighborhood SES, and language. In this retrospective cohort study, we analyzed data on 163 patients who underwent surgical intervention for CHD within 30 days of birth between 2011 and 2020 at the University of Maryland Children's Hospital. A neighborhood SES score was calculated using the mother's address at time of discharge and 6 SES variables from the US Census block group data with a previously published method by Diez Roux et al. Neighborhood SES did not impact the likelihood of receiving a PD of CHD; however, patients of Latino ethnicity were 3.2 times and non-English-preferred language patients were 5.1 times more likely to not receive a PD. Patients whose preferred language was a non-English language received a prenatal diagnosis 5.3 weeks later, resulting in the PD being made in the third trimester rather than the second. Patients from the highest quartile SES received an earlier prenatal diagnosis, although this association was less significant when controlling for insurance type and preferred language. Significant disparities in PD of CHD were seen in patients of Latino ethnicity and patients who prefer non-English language. Better understanding of the root causes of these disparities will be important to guide interventions to reduce these disparities.

Temporal Trend of COVID-19 Clinical Severity and the Ethnic/Racial Disparity: A Report from the Maryland Study Group.

OBJECTIVES: This study aimed to evaluate the temporal trend of novel coronavirus disease 2019 (COVID-19) symptoms and severity of clinical outcomes among pregnant women over a calendar year in the State of Maryland and compare clinical outcomes between different ethnic and racial groups. STUDY DESIGN: We conducted a retrospective, multicenter observational study of the temporal trend of COVID-19 clinical presentation during pregnancy in the State of Maryland. We reviewed consecutive charts of adult pregnant females, aged 18 to 55 years, with laboratory-confirmed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection between March 1, 2020, and February 28, 2021, and managed within the University of Maryland Medical System and Johns Hopkins Medicine. We excluded cases with insufficient data for assessing the COVID-19 diagnosis, pregnancy status, or clinical outcomes. We evaluated the evolution of COVID-19 symptoms at the time of presentation. Also, we compared COVID-19 infection rate, hospitalization rate, oxygen use, and intensive care unit (ICU) admission rates between different ethnic and racial groups. RESULTS: We included 595 pregnant women with laboratory-confirmed COVID-19 over the study period. The prevalence of respiratory and systemic symptoms decreased over time with incidence rate ratios (IRRs) of 0.91 per month (95% confidence interval [CI]: 0.88-0.95) and 0.87 per month (95% CI: 0.83-0.95), respectively. The prevalence of hospitalization, O2 requirement, and ICU admission decreased over time with IRRs of 0.86 per month (95% CI: 0.82-0.91), 0.91 per month (95% CI: 0.84-0.98), and 0.70 per month (95% CI: 0.57-0.85), respectively. The Hispanic and Black populations had a higher COVID-19 infection rate and hospitalization rate than the non-Hispanic White population (p = 0.004, < 0.001, and < 0.001, respectively). CONCLUSION: Understanding the concepts of viral evolution could potentially help the fight against pandemics like COVID-19. Moreover, this might improve the knowledge of how pandemics affect disadvantaged populations and help close the gap in health care inequities. KEY POINTS: · A trade-off between virulence and transmissibility is determined by the natural selection of viruses.. · Understanding the concepts of viral evolution can help the fight against pandemics like COVID-19.. · Evolution of SARS-CoV-2 over time resulted in decreased virulence and increased infectivity..

A pilot study: Application of paired ultrasound simulator training in obstetrics.

OBJECTIVE: Medical trainees in obstetrics must develop competency in fetal ultrasonography. To date, no studies have utilized ultrasound simulator training for basic fetal anatomy with paired didactic coursework. We hypothesize that ultrasound simulator training with paired didactics improves medical trainee competency in fetal ultrasonography. METHODS: A prospective observational study was performed at a tertiary care center during the 2021-2022 academic year. Medical trainees in obstetrics without prior simulator experience could participate. Participants completed ultrasound simulator training with standardized paired didactics and subsequent real-time patient scanning. All images were reviewed by the same physician for competency. Trainees completed 11-point Likert scale surveys at three time points: pre-simulator, post-simulator, and post-real-time patient scanning. Two-tailed student's t-tests with 95% confidence intervals were performed, and p-values <0.05 were considered significant. RESULTS: Of the 26 trainees that completed the training, 96% reported that simulation positively impacted their confidence and ability to perform real-time scanning of patients. Self-reported knowledge of fetal anatomy, ultrasound techniques, and application to clinical obstetrics all significantly increased after simulator training (p < 0.01). CONCLUSIONS: Paired ultrasound simulation with didactic instruction significantly improves medical trainees' knowledge of fetal anatomy and ability to perform fetal ultrasonography. Implementing an ultrasound simulation curriculum may become an essential tool for obstetric residency programs.

Prenatal diagnosis of a germline variant in TRAF7: Importance of accessibility to prenatal exome sequencing in cases of structural fetal anomalies.

Diagnosis of a pathogenic germline TRAF7 missense variant (c.1555 C > T, p.L519F) made on a prenatal basis by exome sequencing (ES) performed on chorionic villi. This case highlights the importance of both higher-level prenatal ultrasounds and the accessibility of ES in making genetic diagnoses in making pregnancy management decisions.

Accuracy of the Standardized Early Fetal Heart Assessment in Excluding Major Congenital Heart Defects in High-Risk Population: A Single-Center Experience.

OBJECTIVE: To evaluate the ability of standardized early fetal heart assessment (EFHA) that includes the 4-chamber view, outflow tract relationship (OTR), and transverse arches views (TAV) of the great arteries in excluding major congenital heart defects (CHDs) in high-risk populations. METHODS: This retrospective study included high-risk pregnancies for CHDs undergoing EFHA at 11-14 weeks of gestation. Risk factors for CHDs were diabetes mellitus, a family history of CHDs, a history of a CHD use of teratogenic medications, seizure disorder, assisted reproductive treatment-conceived pregnancy, presence of at least one of the ultrasound markers: enlarged nuchal translucency (>95th percentile), tricuspid regurgitation, and reversed a-wave in the ductus venosus, presence of an extracardiac or a suspected cardiac anomaly, a high-risk first trimester combined screen result, and multiple pregnancies. EFHA consisted of visualization of 4ChV, OTR, and TAV, with and without power Doppler ultrasound. The primary outcome was the negative predictive value of EFHA in excluding major CHDs. RESULTS: EFHA was performed on 1055 fetuses. Of these, 1024 were used for the final analysis. Of these, 94.9% (n = 923) were singleton. The most common indication for EFHA was maternal DM (n = 231, 22.6%). The sensitivity, specificity, false positive, false negative, and accuracy of EFHA were 93.2%, 99.9%, 1.4%, 0.4%, and 99.5% (P < .0001), respectively, in entire included cases. The performance of EFHA was 88%, 99.9%, 1.4%, 0.4%, and 99.5% (P < .0001) respectively when the terminated cases were excluded. CONCLUSION: Early fetal heart assessment is feasible for screening for major CHDs in high-risk populations. This approach may be expanded to the general obstetric population.

First trimester examination of fetal anatomy: clinical practice guideline by the World Association of Perinatal Medicine (WAPM) and the Perinatal Medicine Foundation (PMF).

This recommendation document follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation. We aim to bring together groups and individuals throughout the world for precise standardization to implement the ultrasound evaluation of the fetus in the first trimester of pregnancy and improve the early detection of anomalies and the clinical management of the pregnancy. The aim is to present a document that includes statements and recommendations on the standard evaluation of the fetal anatomy in the first trimester, based on quality evidence in the peer-reviewed literature as well as the experience of perinatal experts around the world.

A prenatally diagnosed case of Donnai-Barrow syndrome: Highlighting the importance of whole exome sequencing in cases of consanguinity.

Donnai-Barrow syndrome (DBS) is an autosomal recessive disorder characterized by typical craniofacial features, vision and hearing loss, intellectual disability, agenesis of the corpus callosum (ACC), congenital diaphragmatic hernia (CDH), and omphalocele. This condition is associated with loss-of-function mutations in the LRP2 gene. Few cases have been described in the literature. In our case, CDH and ACC were prenatally diagnosed by ultrasound, and the fetus was the product of a first-degree union. Single-nucleotide polymorphism-microarray showed large regions of homozygosity. Whole exome sequencing (WES) was performed and revealed a homozygous frameshift pathogenic variant in LRP2 (c.6978dupG). Here, we present a case of DBS, which diagnosed prenatally via WES in a fetus with CDH and ACC.

Clinical management of coronavirus disease 2019 (COVID-19) in pregnancy: recommendations of WAPM-World Association of Perinatal Medicine.

These guidelines follow the mission of the World Association of Perinatal Medicine, which brings together groups and individuals throughout the world with the goal of improving outcomes of maternal, fetal and neonatal (perinatal) patients. Guidelines for auditing, evaluation, and clinical care in perinatal medicine enable physicians diagnose, treat and follow-up of COVID-19-exposed pregnant women. These guidelines are based on quality evidence in the peer review literature as well as the experience of perinatal expert throughout the world. Physicians are advised to apply these guidelines to the local realities which they face. We plan to update these guidelines as new evidence become available.

Applicability of Standardized Early Fetal Heart Examination in the Obese Population.

OBJECTIVE: This study aimed to evaluate the impact of obesity on early evaluation of fetal cardiac landmarks using a standardized examination method at the time of nuchal translucency scan. METHODS: This was a cross-sectional study of an ongoing prospective cohort at high risk for congenital heart defects. We used a standardized examination protocol using 2-dimensional sonography with power Doppler in the evaluation of fetal cardiac landmarks consisting of 4-chamber view, outflow tract relationship, and transverse arches view. The study population was stratified based on maternal body mass index into nonobese (<30 kg/m2 ) and obese (≥30 kg/m2 ). Groups were compared in terms of satisfactory evaluation of fetal cardiac landmarks, transvaginal sonography use, and scan times required for the evaluations. Subanalysis was performed by further categorizing obesity into nonmorbid obesity (30.0-39.9 kg/m2 ) and morbid obesity (≥40 kg/m2 ). RESULTS: A total of 190 patients were evaluated. Of these, 48.4% (n = 92) were obese. The most common indication for fetal cardiac assessment was maternal pregestational diabetes mellitus (42.6%). Transvaginal sonography was utilized in one nonobese woman (1.4%) and 11 obese women (12%) (P = .002). The satisfactory evaluation of 4-chamber view, outflow tract relationship, transverse arches view, and all views were not significantly different between groups (P > .05). The scan time was about 5 minutes longer in the obese group compared with nonobese group (P = .020). CONCLUSIONS: Obesity does not hamper early evaluation of fetal cardiac landmarks around the time of nuchal translucency scan. However, obese patients are more likely to require transvaginal examinations.

Exposure of the developing heart to diabetic environment and early cardiac assessment: A review.

Hyperglycemia during organogenesis is associated with an increased risk of congenital cardiac defects (CHDs). The pathophysiology leading to CHDs is not completely uncovered. However, elevated oxidative stress is considered to be the primary trigger that causes CHDs in fetuses of diabetic mothers. Maternal diabetes has been found to increase the risk for all types of CHDs. Diabetes may also impact the fetal cardiac performance at all gestational ages. Early detection of CHDs has certain advantages, such as making early decision about termination of pregnancy, enabling early genetic testing, and early reassurance if scan is normal. Combined transabdominal and transvaginal approach at 13-14 weeks of gestation is a reasonable strategy to assess fetal heart in diabetic women. Diagnostic accuracy of early fetal echocardiography has reached to above a reasonable cutoff when it is done in the late first trimester or early second trimester in the hands of expert sonographers. However, the literature is less certain to provide a firm conclusion about functional heart assessment in fetuses of diabetic mothers.

The importance of prenatal 3-dimensional sonography in a case of a segmental overgrowth syndrome with unclear chromosomal microarray results.

PIK3CA-related overgrowth spectrum, caused by mosaic mutations in the PIK3CA gene, is associated with regional or generalized asymmetric overgrowth of the body or a body part in addition to other clinical findings. Three-dimensional ultrasonography (3-D US) has the capability to display structural abnormalities in soft tissues or other organs, thereby facilitating identification of segmental overgrowth lesions. We present a case suspected of having a segmental overgrowth disorder based on 3-D US, whose chromosomal microarray result was abnormal, but apparently was not the cause of the majority of the fetus's clinical features.

Increased fetal epicardial fat thickness: A novel ultrasound marker for altered fetal metabolism in diabetic pregnancies.

OBJECTIVE: To evaluate whether fetal epicardial fat thickness (EFT) differs in diabetic and nondiabetic pregnant women. METHODS: Retrospective case-control study of pregnancies between 24 and 36 weeks complicated by preexisting (PDM) or gestational (GDM) diabetes mellitus, matched one to one with controls for body mass index and gestational age (GA). Epicardial fat was identified as the hypoechogenic area between myocardium and visceral pericardium over the right ventricle and its thickness was measured by a single observer blinded to clinical condition and outcomes. A linear regression analysis was performed to assess the relationship between GA and EFT, and regression lines were compared between diabetics and controls. RESULTS: 53 PDM and 53 GDM pregnant women were matched with controls. With the exception of maternal age, the demographics were similar among groups. EFT increased significantly with advancing gestation in both diabetics and controls (P < 0.0001) and was significantly greater in diabetics than in controls (P < 0.0001). The best fit lines were different between diabetics (EFT = 0.05 × GA + 0.07 mm; R2 = 0.70) and controls (EFT = 0.07 × GA + 0.04 mm; R2 = 0.93) (P < 0.0001). CONCLUSION: Fetal EFT was greater in diabetics than in nondiabetics, and even greater in pregestational diabetics. EFT maybe an additional and/or earlier marker to identify early changes in fetal metabolism before accelerated fetal growth and polyhydramnios is apparent.

Chronic hypoxia alters maternal uterine and fetal hemodynamics in the full-term pregnant guinea pig.

Placental hypoxia is associated with maternal hypertension, placental insufficiency, and fetal growth restriction. In the pregnant guinea pig, prenatal hypoxia during early gestation inhibits cytotrophoblast invasion of spiral arteries, increases maternal blood pressure, and induces fetal growth restriction. In this study the impact of chronic maternal hypoxia on fetal heart structure was evaluated using four-dimensional echocardiography with spatiotemporal image correlation and tomographic ultrasound, and uterine and umbilical artery resistance/pulsatility indexes and fetal heart function were evaluated using pulsed-wave Doppler ultrasound. Pregnant guinea pigs were exposed to normoxia (n = 7) or hypoxia (10.5% O2, n = 9) at 28-30 days gestation, which was maintained until full term (65 days). At full term, fetal heart structure and outflow tracts were evaluated in the four-chamber view. Fetal heart diastolic function was assessed by E wave-to-A wave diastolic filling ratios (E/A ratios) of both ventricles and systolic function by the myocardial performance index (or Tie) of left ventricles of normoxic (n = 21) and hypoxic (n = 17) fetuses. There were no structural abnormalities in fetal hearts. However, hypoxia induced asymmetric fetal growth restriction and increased the placental/fetal weight compared with normoxic controls. Hypoxia increased Doppler resistance and pulsatility indexes in the uterine, but not umbilical, arteries, had no effect on the Tie index, and increased the E/A ratio in left, but not right, ventricles. Thus, prolonged hypoxia, starting at midgestation, increases uterine artery resistance and generates fetal growth restriction at full term. Furthermore, the enhanced cardiac diastolic filling with no changes in systolic function or umbilical artery resistance suggests that the fetal guinea pig systemic circulation undergoes a compensated, adaptive response to prolonged hypoxia exposure.

Prenatal diagnosis of inverted duplication deletion 8p syndrome mimicking trisomy 18.

Inverted duplication deletion of 8p (invdupdel[8p]) is a well-described and uncommon chromosomal rearrangement. The majority of the reported cases have revealed no life-threatening malformations. Although the invdupdel[8p] syndrome in children with central nervous system abnormalities has been reported before, we present the first prenatal microarray diagnosis of invdupdel[8p] syndrome mimicking trisomy 18 due to similar sonographic features. Contrary to reported cases with invdupdel[8p] syndrome, the present case had severe polyvalvular dysplasia and the infant deceased at day 12 of life. In this case, we also emphasize the diagnostic power of microarray analysis in detecting the underlying genetic causes for fetuses with multiple congenital anomalies. © 2017 Wiley Periodicals, Inc.

Arterial and Venous Doppler in Evaluation of the "At-Risk" Fetus.

Our practice utilizes Doppler ultrasound as one of the most objective and effective methods to assess at-risk pregnancies. This review will discuss the application of arterial and venous Doppler techniques in assessing and managing various diseases and conditions for high-risk fetuses.