Cardiac Development and Factors Influencing the Development of Congenital Heart Defects (CHDs): Part I.

The traditional description of cardiac development involves progression from a cardiac crescent to a linear heart tube, which in the phase of transformation into a mature heart forms a cardiac loop and is divided with the septa into individual cavities. Cardiac morphogenesis involves numerous types of cells originating outside the initial cardiac crescent, including neural crest cells, cells of the second heart field origin, and epicardial progenitor cells. The development of the fetal heart and circulatory system is subject to regulatation by both genetic and environmental processes. The etiology for cases with congenital heart defects (CHDs) is largely unknown, but several genetic anomalies, some maternal illnesses, and prenatal exposures to specific therapeutic and non-therapeutic drugs are generally accepted as risk factors. New techniques for studying heart development have revealed many aspects of cardiac morphogenesis that are important in the development of CHDs, in particular transposition of the great arteries.

Environmental Signals.

Environmental factors have long been known to play a role in the pathogenesis of congenital heart disease (CHD), but this has not been a major focus of research in the modern era. Studies of human exposures and animal models demonstrate that demographics (age, race, socioeconomic status), diseases (e.g., diabetes, hypertension, obesity, stress, infection, high altitude), recreational and therapeutic drug use, and chemical exposures are associated with an increased risk for CHD. Unfortunately, although studies suggest that exposures to these factors may cause CHD, in most cases, the data are not strong, are inconclusive, or are contradictory. Although most studies concentrate on the effects of maternal exposure, paternal exposure to some agents can also modify this risk. From a mechanistic standpoint, recent delineation of signaling and genetic controls of cardiac development has revealed molecular pathways that may explain the effects of environmental signals on cardiac morphogenesis and may provide further tools to study the effects of environmental stimuli on cardiac development. For example, environmental factors likely regulate cellular signaling pathways, transcriptional and epigenetic regulation, proliferation, and physiologic processes that can control the development of the heart and other organs. However, understanding of the epidemiology and risk of these exposures and the mechanistic basis for any effects on cardiac development remains incomplete. Further studies defining the relationship between environmental exposures and human CHD and the mechanisms involved should reveal strategies to prevent, diagnose, and treat CHD induced by environmental signals.

Maternal diabetes and risk of offspring congenital heart diseases: the Japan Environment and Children's Study.

BACKGROUND: Few prospective cohort studies have examined the association between maternal diabetes, including pre-pregnancy and gestational diabetes, and the risk of congenital heart disease (CHD) in Asian offspring. METHODS: We examined the association between maternal diabetes and offspring CHD among 97,094 mother-singleton infant pairs in the Japan Environment and Children's Study (JECS) between January 2011 and March 2014. Odds ratios (OR) and 95% confidence intervals (CI) of offspring CHD based on maternal diabetes (pre-pregnancy diabetes and gestational diabetes) were estimated using logistic regression after adjusting for maternal age at delivery, pre-pregnancy body mass index (BMI), maternal smoking habits, alcohol consumption, annual household income, and maternal education. The diagnosis of CHD in the offspring was ascertained from the transcript of medical records. RESULTS: The incidence of CHD in the offspring was 1,132. Maternal diabetes, including both pre-pregnancy diabetes and gestational diabetes, was associated with a higher risk of offspring CHD: multivariable OR (95%CI) = 1.81 (1.40-2.33) for maternal diabetes, 2.39 (1.05-5.42) for pre-pregnancy diabetes and 1.77 (1.36-2.30) for gestational diabetes. A higher risk of offspring CHD was observed in pre-pregnancy BMI ≥25.0 kg/m2 (OR = 2.55, 95% CI: 1.74-3.75) than in pre-pregnancy BMI <25.0 kg/m2 (OR = 1.49, 95% CI: 1.05-2.10, p for interaction = 0.04). CONCLUSIONS: Maternal diabetes, including both pre-pregnancy and gestational, was associated with an increased risk of CHD in offspring.

Association between Maternal Birth Weight and Prevalence of Congenital Malformations in Offspring: The Japanese Environment and Children's Study.

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that an MBW of <2500 g (low MBW) was associated with an increased risk of congenital heart disease (adjusted odds ratio: 1.388, [95% confidence interval: 1.075-1.792]), angioma (1.491 [1.079-2.059]), and inguinal hernia (1.746, [1.189-2.565]), while those with an MBW of ≥4000 g (high MBW) were associated with congenital anomalies of the urinary tract (2.194, [1.261-3.819]) and arrhythmia (1.775, [1.157-2.725]) compared with those with an MBW of 3000-3499 g. Low MBW was associated with cleft lip and/or palate (1.473, [1.052-2.064]), congenital heart disease (1.615, [1.119-2.332]), genital organs (1.648, [1.130-2.405]), hypospadias (1.804, [1.130-2.881]), and inguinal hernia (1.484, [1.189-1.851]) in male infants and CAKUT (1.619, [1.154-2.273]) in female infants, whereas high MBW was associated with congenital heart disease (1.745, [1.058-2.877]) and CAKUT (2.470, [1.350-4.517]) in male infants. The present study is the first to demonstrate a link between MBW and congenital malformations in Japanese children. While these results must be interpreted with caution, MBW should be considered a major predictor of congenital malformation risk.

Association between lipid profile in early pregnancy and the risk of congenital heart disease in offspring: a prospective cohort study.

This study aimed to investigate the association of lipid profile in early pregnancy and the risk of congenital heart disease (CHD) in offspring. This study was a prospective cohort design based on the Fujian Birth Cohort Study in China. We recruited pregnant women at ≤ 14 weeks of gestation between 2019 and 2022, and all participants in this study filled out the questionnaire about periconceptional exposure. Simultaneously, we collected participants' fasting blood samples to measure their lipid profile by automatic biochemical analyzer. The outcome was defined as offspring with CHD. A multivariable logistic regression model was used to calculate adjusted odds ratio (AOR) risk estimates, which indicate the associations between maternal lipid profiles and CHD in offspring. Restricted cubic splines were used to estimate their nonlinear relationship. A total of 21,425 pregnant women with an average gestational age of 11.3 (± 1.40) weeks were included in the analysis. The higher triglyceride (AOR 1.201, 95% CI [1.036, 1.394]), low-density lipoprotein (AOR 1.216, 95% CI [1.048, 1.410]), apolipoprotein B (Apo B) (AOR 2.107, 95% CI [1.179, 3.763]) levels were correlated with increased odds of CHD in offspring, while high-density lipoprotein (OR 0.672, 95% CI [0.490, 0.920]) related with decreased odds of CHD in offspring. The restricted cubic spline suggested a nonlinear relationship between total cholesterol (TC) levels and the risk of CHD in offspring (P = 0.0048), but no significant nonlinear relationships were found in other lipid profile. Apolipoprotein A was not related to the risk of CHD in offspring as either a continuous variable or a hierarchical variable. Elevated lipid profile in early pregnancy levels are associated with an increased risk of CHD in offspring. Additionally, there is a non-linear relationship between TC levels and the risk of CHD in offspring.

Correlation between essential and toxic elements in maternal blood during early pregnancy and atrial septal defects/ventricular septal defects/patent ductus arteriosus in offspring.

BACKGROUND: Congenital heart defects (CHDs) are the most common congenital malformation in the world. Recent studies have found that essential and toxic trace element levels may play a crucial role in the risk of neonatal malformation. However, the relationships between element levels in early pregnancy and CHD risk among humans remain unclear. This study investigates the association between maternal essential element (copper [Cu], zinc [Zn], calcium [Ca], manganese [Mg] and iron [Fe]) and toxic element (lead [Pb] and cadmium [Cd]) levels during early pregnancy and CHDs. METHODS: A hospital-based case-control study was conducted, including 181 cases and 218 controls. Eligible participants underwent antenatal examination during gestational weeks 11-14 and trace element levels were detected by the atomic absorption method. Multi-variable logistic regression was used to examine the associations between the level of maternal trace elements and CHD risks. RESULTS: Higher levels of Ca in early pregnancy were associated with lower risk of ASD/VSD risks. Moreover, higher Fe, Pb, and Cd levels in the first trimester were associated with higher risks of all CHD and the subtypes risks, and the tests for trend were significant (all p < .05). The restricted cubic spline analysis showed that there was a nonlinear inverted u-shaped dose-response relationship between levels of Zn, Pb, and Cd in the first trimester and risk of CHDs (non-linearity test p < .05). CONCLUSIONS: A moderate increase in Zn and Ca levels and a decrease in Pb and Cd levels during early pregnancy are needed to reduce the incidence of CHDs in the Chinese population.

Maternal Diabetes and Overweight and Congenital Heart Defects in Offspring.

Importance: Maternal diabetes and overweight or obesity are known to be associated with increased risk of congenital heart defects (CHDs) in offspring, but there are no large studies analyzing outcomes associated with these factors in 1 model. Objective: To investigate the association of maternal diabetes and overweight or obesity with CHDs among offspring in 1 model. Design, Setting, and Participants: This nationwide, population-based register study was conducted in a birth cohort from Finland consisting of all children born between 2006 and 2016 (620 751 individuals) and their mothers. Data were analyzed from January 2022 until November 2023. Exposures: Maternal prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), categorized as underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9), and obesity (≥30), was assessed. Maternal diabetes status, classified as no diabetes, type 1 diabetes (T1D), type 2 or other diabetes, and gestational diabetes, was assessed. Main Outcomes and Measures: Odds ratios (ORs) of isolated CHDs in children were found. In addition, 9 anatomical CHD subgroups were studied. Results: Of 620 751 children (316 802 males [51.0%]; 573 259 mothers aged 20-40 years [92.3%]) born in Finland during the study period, 10 254 children (1.7%) had an isolated CHD. Maternal T1D was associated with increased odds of having a child with any CHD (OR, 3.77 [95% CI, 3.26-4.36]) and 6 of 9 CHD subgroups (OR range, 3.28 [95% CI, 1.55-6.95] for other septal defects to 7.39 [95% CI, 3.00-18.21] for transposition of great arteries) compared with no maternal diabetes. Maternal overweight was associated with left ventricular outflow tract obstruction (OR, 1.28 [95% CI, 1.10-1.49]) and ventricular septal defects (OR, 0.92 [95% CI, 0.86-0.98]), and obesity was associated with complex defects (OR, 2.70 [95% CI, 1.14-6.43]) and right outflow tract obstruction (OR, 1.31 [95% CI, 1.09-1.58]) compared with normal maternal BMI. Conclusions and Relevance: This study found that maternal T1D was associated with increased risk for most types of CHD in offspring, while obesity and overweight were associated with increased risk for complex defects and outflow tract obstruction and decreased risk for ventricular septal defects. These different risk profiles of T1D and overweight and obesity may suggest distinct underlying teratogenic mechanisms.

Maternal and neonatal factors associated with cesarean delivery in a cohort of pregnancies complicated by prenatally diagnosed congenital heart disease.

BACKGROUND: Pregnancies with prenatally diagnosed congenital heart disease (CHD) have increased cesarean delivery (CD) rates, with no outcome improvement. OBJECTIVE: We aim to examine indications for delivery, indications for CD and risk factors associated with CD. STUDY DESIGN: Retrospective cohort of 322 singleton pregnancies prenatally diagnosed with moderate to severe CHD. We compared maternal and fetal factors correlated with delivery route. RESULTS: CD rate was 46% (95% CI 40, 51%). Of all CD, 31.3% (95% CI 23.8, 38.7) were secondary to urgent fetal indications. However, 79.7% of inductions resulted in vaginal delivery (VD). Factors associated with CD include morbid obesity (RR 3.0, 95% CI 1.5, 6.1), diabetes (RR 3.9, 95% CI 2.0, 7.3) and severe pre-eclampsia (6.0, 95% CI 1.7, 21.4). Of the 10 most frequent CHD diagnoses, only hypoplastic-left-heart was associated with CD (OR 1.9, 95% CI 1.02, 3.4). CONCLUSIONS: Although the CD rate is higher in fetal CHD, most indications for CD are maternal.

The Impact of Nasal Intubation on Feeding Outcomes in Neonates Requiring Cardiac Surgery: A Randomized Control Trial.

Neonates who require surgery for congenital heart disease (CHD) frequently have difficulty with oral feeds post-operatively and may require a feeding tube at hospital discharge. The purpose of this study was to determine the effect of oral or nasal intubation route on feeding method at hospital discharge. This was a non-blinded randomized control trial of 62 neonates who underwent surgery for CHD between 2018 and 2021. Infants in the nasal (25 patients) and oral (37 patients) groups were similar in terms of pre-operative risk factors for feeding difficulties including completed weeks of gestational age at birth (39 vs 38 weeks), birthweight (3530 vs 3100 g), pre-operative PO intake (92% vs 81%), and rate of pre-operative intubation (22% vs 28%). Surgical risk factors were also similar including Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category (3.9 vs 4.1), shunt placement (32% vs 41%), cardiopulmonary bypass time (181 vs 177 min), and cross-clamp time (111 vs 105 min). 96% of nasally intubated patients took full oral feeds by discharge as compared with 78% of orally intubated infants (p = 0.05). Nasally intubated infants reach full oral feeds an average of 3 days earlier than their orally intubated peers. In this cohort of patients, nasally intubated infants reach oral feeds more quickly and are less likely to require supplemental tube feeding in comparison to orally intubated peers. Intubation route is a potential modifiable risk factor for oral aversion and appears safe in neonates. The study was approved by the University of Virginia Institutional Review Board for Health Sciences Research and was retrospectively registered on clinicaltrials.gov (NCT05378685) on May 18, 2022.

Detection of severe congenital heart defects in live-born infants in Norway 2017-2020.

AIM: The aims of this nationwide retrospective cohort study were to determine the time and causes of detection of severe congenital heart defects (CHDs) in live-born infants in Norway between 2017 and 2020. METHODS: Information regarding live-born infants with severe CHDs was retrieved from national registries and medical records. RESULTS: A total of 219 776 infants were born in Norway from 01.01.2017 to 31.12.2020. Severe CHDs were diagnosed in 442 (0.2%) infants. Of these, 376 (85%) infants were diagnosed either prenatally (n = 203, 46%) or before discharge from hospital after birth (n = 173, 39%). A total of 56 (13%) infants were discharged with undetected CHDs. Time of detection was unknown in 10 cases (2%). The most frequent undetected CHDs at discharge were coarctation of the aorta/aortic arch hypoplasia (n = 24), atrioventricular septal defect (n = 13), anomalous pulmonary venous connection (n = 5) and coronary artery anomalies (n = 4). Seven (13%) children with undetected CHD experienced circulatory collapse out of hospital. CONCLUSION: Most infants with severe CHDs in Norway were identified prior to hospital discharge. However, some infants were discharged undiagnosed. Awareness of undetected CHDs and immediate cardiac assessment in infants with signs of circulatory failure early in life are still important.

Short-Term Mortality Among Pediatric Patients With Heart Diseases Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

BACKGROUND: Veno-arterial extracorporeal membrane oxygenation serves as a crucial mechanical circulatory support for pediatric patients with severe heart diseases, but the mortality rate remains high. The objective of this study was to assess the short-term mortality in these patients. METHODS AND RESULTS: We systematically searched PubMed, Embase, and Cochrane Library for observational studies that evaluated the short-term mortality of pediatric patients undergoing veno-arterial extracorporeal membrane oxygenation. To estimate short-term mortality, we used random-effects meta-analysis. Furthermore, we conducted meta-regression and binomial regression analyses to investigate the risk factors associated with the outcome of interest. We systematically reviewed 28 eligible references encompassing a total of 1736 patients. The pooled analysis demonstrated a short-term mortality (defined as in-hospital or 30-day mortality) of 45.6% (95% CI, 38.7%-52.4%). We found a significant difference (P<0.001) in mortality rates between acute fulminant myocarditis and congenital heart disease, with acute fulminant myocarditis exhibiting a lower mortality rate. Our findings revealed a negative correlation between older age and weight and short-term mortality in patients undergoing veno-arterial extracorporeal membrane oxygenation. Male sex, bleeding, renal damage, and central cannulation were associated with an increased risk of short-term mortality. CONCLUSIONS: The short-term mortality among pediatric patients undergoing veno-arterial extracorporeal membrane oxygenation for severe heart diseases was 45.6%. Patients with acute fulminant myocarditis exhibited more favorable survival rates compared with those with congenital heart disease. Several risk factors, including male sex, bleeding, renal damage, and central cannulation contributed to an increased risk of short-term mortality. Conversely, older age and greater weight appeared to be protective factors.

Risk Factors of Congenital Heart Defects among Bangladeshi Population.

Etiology of congenital heart defects are complex and possibly lie within the interaction of environmental exposures and inherited factors. Exploration of the contribution of environmental risk factors that are potentially modifiable impeded the prevention of CHDs. This study was conducted to evaluate the environmental risk factors of CHD. It was a case control study, conducted from July 2018 to June 2019 in Paediatric Cardiology department of Dhaka Shishu (Children) Hospital, Bangladesh. Parents of the children with CHDs visiting the out-patient department were considered as case. Control was taken from parents of the children not having congenital heart disease. Data were collected by face-to-face interview using a structured questionnaire containing all the variables of interest and analyzed by using SPSS version 21.0. Majority of the respondents were from rural area (86.9% and 80.0% in case and control group respectively) and CHD was found significantly higher in rural population (p<0.05). Consanguinity was present in 8.9% in case group and CHD was found significantly higher among children born to consanguineous parents (p<0.05). Most of the mother (65.4%) had completed primary level of education however 11.9% mother was illiterate in case group. CHD was found significantly higher among illiterate mothers (p<0.05). Most of the respondents belonged to lower and lower-middle class family (83.1% and 75.7% in case and control group respectively) and CHD was found significantly higher among them (p<0.05). Mothers exposed to passive smoking and in stress during pregnancy period, CHD was significantly higher (p<0.05). No significant association was found between maternal drug use and infection during pregnancy period with CHD (p<0.05). Maternal illiteracy, residing in rural areas, low and lower- middle class socioeconomic status, consanguineous marriage, exposed to passive smoking and stress during pregnancy period have been significantly associated with CHDs.

Recommendations for Centers Performing Pediatric Heart Surgery in the United States.

Care and outcomes for the more than 40,000 patients undergoing pediatric and congenital heart surgery in the United States annually are known to vary widely. While consensus recommendations have been published across numerous fields as one mechanism to promote a high level of care delivery across centers, it has been more than two decades since the last pediatric heart surgery recommendations were published in the United States. More recent guidance is lacking, and collaborative efforts involving the many disciplines engaged in caring for these children have not been undertaken to date. The present initiative brings together professional societies spanning numerous care domains and congenital cardiac surgeons, pediatric cardiologists, nursing, and other healthcare professionals from diverse programs around the country to develop consensus recommendations for United States centers. The focus of this initial work is on pediatric heart surgery, and it is recommended that future efforts focus in detail on the adult congenital population. We describe the background, rationale, and methodology related to this collaborative effort, and recommendations put forth for Essential Care Centers (essential services necessary for any program), and Comprehensive Care Centers (services to optimize comprehensive and high-complexity care), encompassing structure, process, and outcome metrics across 14 domains.

Neighborhood location and nutritional resources as a risk factor for congenital heart disease in the fetus.

BACKGROUND: Congenital heart disease (CHD) is the most common birth defect, influenced by maternal health, environmental conditions, and genetics. Maternal health and nutrition, particularly maternal diabetes, is a modifiable risk factor for development of CHD in the fetus. However, the importance of food access during pregnancy on the development of CHD remains unknown. The objective of this study was to investigate the association between maternal neighborhood characteristics, particularly food access, and occurrence of prenatally diagnosed CHD. METHODS: A retrospective case series studied maternal-fetal dyads with prenatally diagnosed CHD between 2019 and 2021 in Washington, DC. Moran's I of maternal addresses evaluated geographic clustering of disease. Negative binomial regression assessed association between census tract demographics and population-adjusted CHD rate. RESULTS: A total of 307 dyads were analyzed. Global Moran's I showed significant CHD clustering (p-value = .004). However, degree of clustering was not clinically meaningful. After adjusting for neighborhood socioeconomic status, residing in food deserts was not a predictor for CHD. However, neighborhoods with a higher percentage of households receiving Supplemental Nutrition Assistance Program (SNAP) benefits were associated with higher rates of conotruncal heart defects (Incident Rate Ratio [IRR] = 1.04, CI = 1.01-1.08) and aggregate CHD (IRR = 1.03, CI = 1.01-1.05). CONCLUSIONS: Neighborhood location and food access were not associated with CHD. However, increased enrollment in SNAP was associated with higher rates of CHD. The association between CHD and SNAP benefits warrants further exploration. Understanding food access and maternal nutrition may illuminate disparities in the burden of CHD.

The Effects of Cardiac Implantable Electronic Device Personal Protective Equipment Use in Patients with Pediatric and Adult Congenital Heart Disease.

Pediatric and adult congenital heart disease (ACHD) patients encounter physical and emotional barriers. Cardiac implantable electronic devices (CIEDs), including pacemakers and implantable cardiac defibrillators (ICD) often compound these issues. Patient fear associated with damaging the CIED system can lead to avoidance of physical activity and reduced quality of life (QOL). CIED personal protective equipment (PPE) is a potential treatment for decreasing this fear. We sought to determine the effects of CIED PPE use in the pediatric and ACHD population. Patients 5 years or older with a CIED at a single pediatric and ACHD heart rhythm center received a CIED protector and customized athletic shirt. QOL was assessed using the PedsQL TM 4.0 SF15 prior to and after 6-12 months. Of the 77 patients enrolled, 26 completed repeat assessment. The mean age at enrollment was 15.6 years (range 5-36) with a mean device age of 2.2 years (< 1-10 years). Pacemakers were present in 77% and 23% had ICDs. The PPE was used in 92% with no PPE malfunction. Fear associated with physical activity was reduced, z = - 4, p < 0.001, with a large effect size (r = 0.55). There was a trend toward increased physical activity. Total QOL scores improved, z = - 2.771, P < 0.05, with a medium effect size (r = 0.4). This first study of CIED PPE in children shows that providing CIED PPE to pediatric and ACHD patients may decrease their fear of damaging their device system, increasing physical activity levels, and improving quality of life.

Application of high-flow nasal cannula in fibreoptic bronchoscopy after congenital heart surgery: a retrospective cohort study.

BACKGROUND: The purpose of this study was to compare the effectiveness and safety of high-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) in fibreoptic bronchoscopy (FB) after congenital heart surgery (CHS) in children. METHODS: We did a retrospective cohort study using patients from the electronic medical record system of Fujian Children's Hospital in China. The study population was children who underwent FB in the cardiac intensive care unit after CHS for 1 year (May 2021-May 2022). Children were classified into HFNC and COT groups according to their oxygen therapy during FB. The primary outcome was oxygenation indices during FB, including pulse oximeter oxygen saturation (SpO2) and transcutaneous oxygen tension (TcPO2) during FB. Secondary outcomes were the number of interruptions during FB and their causes, and complications after FB. RESULTS: We identified 107 children from the electronic medical record system, and 102 children after CHS were finally included in the study (53 in the HFNC group and 49 in the COT group). During the FB examination, TcPO2 and SpO2 were significantly higher in the HFNC group than in the COT group (TcPO2: 90.3±9.3 vs 80.6±11.1 mm Hg; SpO2: 95.6±2.5 vs 92.1%±2.0%, p<0.001) and the transcutaneous carbon dioxide tension was significantly lower than in the COT group (39.6±3.0 vs 43.5±3.9 mm Hg, p<0.001). During the FB, a total of 20 children in the COT group had 24 interruptions, and 8 children in the HFNC group had 9 interruptions (p=0.001). In terms of postoperative complications, eight cases had complications in the COT group and four complications in the HFNC group (p=0.223). CONCLUSIONS: Among children undergoing FB after CHS, the application of HFNC was associated with better oxygenation and fewer procedural interruptions compared with COT, without an increased risk of postoperative complications.

Oxidative balance scores and neural crest cell-related congenital anomalies.

Oxidative stress and redox imbalance adversely affect embryonic development. We developed two oxidative balance scores (OBS) that include dietary and nondietary exposures. We hypothesized that higher scores (i.e., lower oxidative stress) would be associated with lower risk of neural tube defects, orofacial clefts, conotruncal heart defects, and limb deficiencies. We used data from the National Birth Defects Prevention Study to create a dietary OBS based on intake of 13 nutrients and an overall OBS that included the 13 nutrients and eight additional nondietary factors related to oxidative balance (e.g., smoking). We used logistic regression to examine odds ratios associated with having low or high scores (i.e., <10th or >90th percentiles). Continuous models indicated reduced odds associated with high versus low scores (i.e., comparing odds at the 90th versus 10th percentile values of the distribution) on the overall OBS for cleft lip with or without cleft palate [adjusted odds ratio (aOR) 0.72, 95% confidence interval (CI) 0.63-0.82], longitudinal limb deficiency (aOR 0.73, CI 0.54-0.99), and transverse limb deficiency (aOR 0.74, CI 0.58-0.95); increased odds for anencephaly (aOR 1.40, CI 1.07-1.84); and primarily nonsignificant associations with conotruncal heart defects. Results for the dietary OBS were similar. This study provides some evidence that oxidative stress contributes to congenital anomalies related to neural crest cell development.

Maternal exposure to housing renovation during the periconceptional period and the risk of offspring with isolated congenital heart disease: a case-control study.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent birth defect in recent decades. The aim of this research was to examine the association between maternal housing renovation exposure during the periconceptional period and isolated congenital heart disease (CHD) in their offspring. METHODS: A multi-hospitals case-control study was conducted from six tertiary A hospitals in Xi'an, Shaanxi, Northwest China based on questionnaires and interviews to address this question. The cases included fetuses or newborns diagnosed with CHD. Controls consisted of healthy newborns without birth defects. In total, 587 cases and 1180 controls were enrolled in this study. The association between maternal periconceptional housing renovation exposure and isolated CHD for offspring was assessed by estimating odds ratios (OR) with multivariate logistic regression models. RESULTS: After adjusting for potential confounding variables, it was found that maternal exposure to home improvement projects was associated with a higher probability of isolated CHD in offspring (adjusted OR: 1.77, 95% CI: 1.34, 2.33). Additionally, the risk of the ventricular septal defect (VSD) and patent ductus arteriosus (PDA) for CHD types was significantly associated with maternal exposure to housing renovations (VSD: adjusted OR = 1.56, 95% CI: 1.01, 2.41; PDA: adjusted OR = 2.50, 95% CI: 1.41, 4.45). CONCLUSIONS: Our study suggests that maternal exposure to housing renovation during the periconceptional period was associated with an increased risk of isolated CHD in offspring. Consequently, it would be beneficial to avoid living in a renovated home from 12 months before pregnancy through the first trimester to lower isolated CHD in infants.

Increased gestational palmitic acid predisposes offspring to congenital heart disease.

Identification of the causes for congenital heart disease (CHD) is a prerequisite for precise prevention and personalized treatment of CHD. Zhao et al.1 show increased that gestational serum palmitic acid (PA) predisposes offspring to CHD by perturbating the MARS/K-Hcy/GATA4 signaling pathway.