Birth Defects Research最新文献

Objective: To determine whether there is a higher rate of major fetal congenital heart diseases (CHDs) at first-trimester scan in pregnancies conceived by assisted reproductive technology (ART).

Methods: A retrospective study was conducted from 2014 to 2022. It included 20,009 singleton pregnancies undergoing ultrasound between 11 and 15 weeks for first-trimester aneuploidy screening or referral for suspected fetal abnormality. Fetal heart assessment was performed through sequential analysis. In cases of CHDs, extracardiac malformations, or other risk factors for major aneuploidies, fetal karyotype evaluation was conducted. CHDs were categorized as major or minor.

Results: A CHD was diagnosed in 133 (0.7%) of 18,532 natural pregnancies and 14 (0.9%) of 1477 ART pregnancies. The prevalence of major CHDs in natural pregnancies was 0.5%, with no significant difference compared to ART pregnancies (0.7%; p = 0.47). Overall, 48 CHD cases (43.2%) were associated with extracardiac abnormalities, with no differences between natural and ART pregnancies (p = 0.38). The frequency of abnormal karyotype and isolated CHDs (normal karyotype and no extracardiac abnormalities) also did not differ.

Conclusion: The rate of major CHDs detectable at the end of the first trimester does not differ between ART and natural pregnancies.

Background: This review aimed to investigate the effect of melatonin on the maternal side of the implantation process. Additionally, reproductive factors involved in changing melatonin levels and vice versa, will also be discussed.

Methods: The authors collected the relevant articles published until 2024 and these are carefully selected from PubMed, Embase, Google scholar databases on the basis of related keywords.

Results: Melatonin could improve the endometrial receptivity and has been shown to act directly on several reproductive events, including folliculogenesis, oocyte maturation, and corpus luteum (CL) formation. Melatonin administration reduces oxidative stress and directly acts on its membrane receptors and melatonin thyroid hormone receptors (MT1 and MT2). Also, melatonin displays effects on the earliest phases of pregnancy and during the whole gestational period. Many studies have reported the anticancer effect of melatonin against a myriad of women cancer types. A new report by WHO revealed that around 17.5% of the adult population experience infertility, showing the urgent need to increase access to affordable, high-quality fertility care for those in need.

Conclusions: This study shows that melatonin is present in the ovary and the placenta and has positive effects in the maternal reproductive system.

Background: Congenital heart disease (CHD) is the most common birth defect. Environmental risk factors, including air pollution, are increasingly identified as contributors to the risk profile of CHD. We sought to investigate the temporal association between frequency and severity of fetal CHD with air quality in the D.C. metropolitan region.

Methods: We queried all fetal diagnoses of CHD at a tertiary care center over a 5-year period, inclusive of a wildfire smoke event. We categorized each case as critical or non-critical CHD and assigned the case to the estimated month of delivery. We used descriptive statistics to show temporal trends in fetal CHD and the relationship with publicly available air quality data.

Results: Of the 685 CHD cases, approximately 60% were considered critical CHD. The highest number of cases occurred in March 2024 (coincident with a periconception period in June 2023 during peak wildfire smoke exposure). An additional peak in CHD cases in February 2023 also coincided with a worse air quality peak during the cardiac embryonic period. However, there was no change in the percentage of critical CHD during these peaks.

Conclusion: Our work highlights the possibility of environmental pollution, specifically wildfire smoke exposure, as a risk factor for fetal CHD.

Introduction: The human face develops through a complex sequence of growth and fusion events involving multiple pharyngeal arch derivatives. Disruptions in these processes can result in congenital anomalies such as cleft lip and/or palate (CL/P), which occur in approximately 1.6 per 1000 live births in Europe. Patients with CL/P often experience difficulties regarding feeding and speech, and studies suggest an increased risk of psychosocial difficulties. Understanding the morphological development and timing of secondary palate formation is essential for clarifying the pathogenesis of CL/P and identifying critical developmental periods during pregnancy. In this study, we aimed to evaluate the timing and morphological changes of the secondary palate in human embryos between Carnegie Stages 17-23 and fetuses aged 9-11 weeks post-conception (PC).

Methods: Histological sections and micro-CT scans of 26 human specimens, evenly distributed across these developmental stages, were analyzed.

Results: The results showed that palatal shelves first appear at CS18 and continue vertical outgrowth until CS22. At CS22, the shelves start to reorient horizontally and further extend medially. Shelf contact is observed at CS23, marking the onset of fusion, which is completed during or after 9 weeks PC.

Conclusions: These findings refine the timeline of human secondary palate development. Importantly, identifying this critical developmental window suggests that current guidelines for administering medications during early pregnancy should be reevaluated, as drug exposure during this sensitive period may increase the risk of palatal malformations.

Introduction: Most complementary and alternative medicines (CAMs) lack clinical safety regarding use in pregnancy, yet they are freely available and do not require a prescription. While all new conventional medicines are assessed for safety during pregnancy, CAMs are exempt. In vitro testing potentially provides a rapid screening method to support risk assessment. Whole rat embryo culture can be used to identify the impact of chemicals on the embryonic heart rate. There is clear evidence that slowing of the embryonic heart rate (bradycardia) can cause spontaneous abortions and fetal malformations. The aim of this study was to examine the effect of four commonly used CAMs on the embryonic heart rate in vitro. A risk assessment was then generated from the results.

Methods: Gestation day 13 rat embryos were exposed to the active ingredient of four herbal medicines: allicin (garlic), epigallocatechin-gallate (green tea), ginsenoside Rg3 (found in ginseng), and berberine (goldenseal). All ingredients caused embryonic bradycardia.

Results and conclusion: The margin of safety was acceptable for EGCG and ginsenoside Rg3 but could not be calculated for allicin due to lack of pharmacokinetic data. The margin of safety for berberine is also likely to be acceptable under most conditions.

Background: Congenital anomalies (CAs) are a major cause of childhood mortality and disability in low- and middle-income countries. Our study explored caregiver experiences of infants with major CAs in Kenya and co-developed interventions using human-centered design (HCD).

Methods: We conducted a qualitative study at Kenya's second largest referral hospital (August 2023 to January 2024). Thirty-one caregivers of 23 infants with major CAs completed interviews on experiences and care needs, analyzed thematically using the socio-ecological model (individual, family, healthcare, and community domains). We conducted three HCD workshops with 19 healthcare providers and 15 caregivers to co-develop interventions to improve CA services.

Results: Caregivers reported emotional distress, stigma, and financial and geographic barriers to care. Key healthcare challenges included limited antenatal diagnosis, inadequate provider communication, insufficient peer support, and poor access to CA information. Community stigma contributed to parental isolation and distress, though social and spiritual networks offered coping support. Workshop participants identified stigma and fragmented care as critical issues and proposed feasible interventions, including caregiver support groups, dedicated counselors, provider training, integrated community counseling, improved infrastructure, and stronger support networks to enhance person-centered care.

Conclusions: Engaging caregivers and providers through HCD highlighted major psychosocial and healthcare barriers and generated contextually relevant strategies to improve care for infants with CAs in Kenya. Future research should evaluate the implementation and effects of these interventions on patient- and family-centered outcomes.

Background: Prenatal alcohol exposure can cause fetal alcohol syndrome, but genetic variation can account for some of the observed differential susceptibility to alcohol-induced birth defects. Here we investigate an inbred mouse strain, 129S1/SvImJ (129S1), for its potential susceptibility to alcohol- and Sonic hedgehog pathway inhibitor-induced craniofacial birth defects and the ways complex genetic factors work to alter susceptibility compared to the highly alcohol-susceptible strain, the C57BL/6J (B6J).

Methods: 129S1 pregnant females were treated with alcohol (two doses of 2.9 g/kg), CP-55,940 (2.0 mg/kg), vismodegib (40 or 80 mg/kg), or smoothened agonist (12 mg/kg) during gastrulation or neurulation, then fetuses were assessed for defects. Gastrulation- and neurulation-stage embryo gene expression and apoptosis were also analyzed.

Results: 129S1 mice are completely resistant to alcohol-induced craniofacial birth defects despite high blood alcohol concentrations compared to other alcohol-susceptible mouse strains. This strain is also resistant to craniofacial birth defects after exposure to a synthetic cannabinoid, CP-55,940, and vismodegib. All three drugs inhibit the Sonic hedgehog (Shh) pathway. 129S1 embryos have higher basal expression of two key Shh-related mRNAs, Smo and Efcab7, and lower apoptosis after alcohol compared to B6J embryos. 129S1 embryos are more susceptible to birth defects after treatment with a Shh pathway agonist, smoothened agonist (SAG), than B6J embryos.

Conclusions: 129S1 embryos have higher expression of key Shh pathway genes and low apoptosis after alcohol, which may contribute to the alcohol-resistant phenotype seen in the 129S1/SvImJ strain, adding to the understanding of protective genetic factors in alcohol teratogenesis.

Background: Biliary atresia is a rare but severe congenital anomaly associated with substantial morbidity and mortality in early childhood. Population-based estimates of survival, surgical management, and liver transplantation across Europe remain limited. This study aimed to describe mortality and morbidity among children born with biliary atresia using multinational population-based data.

Methods: We investigated children diagnosed with biliary atresia across nine registries from five countries within the European surveillance of congenital anomalies network (EUROCAT), covering births from 1995 to 2014. The data were linked to hospital databases and adjusted for regional differences and follow-up length.

Results: Our cohort included 171 children, with an infant mortality rate of 12.3% (95% CI: 7.8-17.6) and a mortality rate before age five of 18.5% (95% CI: 10.7-27.7). Among these children, 151 had undergone surgery, including 133 who received the Kasai procedure by the age of 1 year at a median age of 57 days (95% CI: 51-62 days). By age five, 37% (adjusted percentage, 95% CI: 30-44) had undergone liver transplantation, with the median age at transplantation being 318 days (95% CI: 244-391 days). Median age at death in the first year was over 6 months and was not immediately after surgery.

Conclusion: The high mortality and the substantial need for liver transplantation within the first year of life underline the severity of biliary atresia. This highlights the urgent need for further research into pregnancy exposures that may contribute to this rare but severe congenital anomaly to develop primary prevention strategies.

Background: MotherToBaby (MTB) is a teratogen information service that provides information about exposures during pregnancy and breastfeeding to the public and healthcare providers. During the Coronavirus Disease of 2019 (COVID-19) pandemic, MTB received an influx of queries regarding the teratogenicity of the virus and the vaccine. The purpose of this study was to assess the frequency and type of exposures asked about prior to the onset of the COVID-19 pandemic through March 2022 and to evaluate the demographics of individuals who made inquiries.

Methods: Data from MTB contacts (2018-2022) were accessed through a data-sharing agreement. The data were cleaned and standardized by coding all exposures into 11 established categories before linking demographic and exposure files into a single dataset. Analyses included descriptive statistics, chi-square tests, and logistic regression conducted in Excel and STATA 17.0, with statistical significance set at a 0.01% error rate.

Results: The total number of contacts increased from 2019 to 2022, and the exposure category with the highest number of contacts was prescription medications, followed by COVID-19-related exposures. Peaks in the number of contacts relating to COVID-19 correlate with various pandemic milestones, such as when vaccines were approved by the U.S. Food and Drug Administration (FDA).

Conclusion: These data provide valuable information for healthcare providers and agencies, such as the Centers for Disease Control and Prevention (CDC), to better prepare for future pandemics and epidemics.

Background: Hypospadias is one of the most common genital defects in boys, affecting about 1 in 125 live-born boys. Several studies have examined the association between a single environmental exposure and risk of hypospadias, but few have examined the possible effects of multiple environmental exposures simultaneously. Thus, we aimed to address this gap by examining the association between cumulative maternal prenatal environmental exposures and hypospadias occurrence in offspring.

Methods: We conducted a retrospective cohort study using data from 2006 to 2010 Arkansas environmental quality index (EQI), its domains (air, water, land, sociodemographic, and built) and related county-level estimates, matched to data on infants diagnosed with hypospadias and identified from the Arkansas Reproductive Health Monitoring System born 2005-2012. We classified the EQI and its domains into quartiles. Crude and adjusted prevalence ratios (PR) and 95% CI were estimated with Poisson regression analyses with cluster-robust standard error to estimate the association between EQI and the prevalence of hypospadias.

Results: There was no statistically significant association between boys born in areas with fair environmental quality compared to those born in areas with better environmental quality (adjusted PR = 1.01; 95% CI = 0.86, 1.18). For the air domain, we observed a higher prevalence of hypospadias among boys born to women living in areas with fair air quality compared to those living in areas with excellent air quality (adjusted PR = 1.18; 95% CI = 1.01, 1.39).

Conclusion: Our results suggest that there was no significant association between overall poor environmental quality index and the prevalence of hypospadias. However, poorer air quality was associated with a higher prevalence of hypospadias among offspring.