Embryonic Lethal Phenotyping to Identify Candidate Genes Related with Birth Defects.

Congenital birth defects contribute significantly to preterm birth, stillbirth, perinatal death, infant mortality, and adult disability. As a first step to exploring the mechanisms underlying this major clinical challenge, we analyzed the embryonic phenotypes of lethal strains generated by random mutagenesis. In this study, we report the gross embryonic and perinatal phenotypes of 55 lethal strains randomly picked from a collection of mutants that carry piggyBac (PB) transposon inserts. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested most of the analyzed mutations hit genes involved in heart and nervous development, or in Notch and Wnt signaling. Among them, 12 loci are known to be associated with human diseases. We confirmed 53 strains as embryonic or perinatal lethal, while others were subviable. Gross morphological phenotypes such as body size abnormality (29/55, 52.73%), growth or developmental delay (35/55, 63.64%), brain defects (9/55, 16.36%), vascular/heart development (31/55, 56.36%), and other structural defects (9/55, 16.36%) could be easily observed in the mutants, while three strains showed phenotypes similar to those of human patients. Furthermore, we detected body weight or body composition alterations in the heterozygotes of eight strains. One of them was the TGF-ß signaling gene Smad2. The heterozygotes showed increased energy expenditure and a lower fat-to-body weight ratio compared to wild-type mice. This study provided new insights into mammalian embryonic development and will help understand the pathology of congenital birth defects in humans. In addition, it expanded our understanding of the etiology of obesity.

Global, regional, and national incidence and mortality of congenital birth defects from 1990 to 2019.

The study aims to estimate the trends in incidence and mortality of congenital birth defects at global, regional, and national levels from 1990 to 2019. Annual incident cases, age-standardized incidence rates (ASIRs), deaths, and age-standardized mortality rates (ASMRs) of congenital birth defects during 1990-2019 were collected from Global Burden of Diseases Study 2019. We calculated percentage of relative changes and estimated annual percentage changes (EAPCs) to quantify temporal trends, and explored potential influence factors of EAPCs using Pearson correlation. Globally, total incident cases and deaths of congenital birth defects were 8.52 million and 0.55 million in 2019. Congenital heart anomalies were the major category of congenital birth defects worldwide in 2019. From 1990 to 2019, the ASIR remained stable (EAPC=0.01, 95% CI -0.03 to 0.05), whereas the ASMR decreased (EAPC=-1.79, 95% CI -1.84 to -1.74). The most pronounced increase in ASIR occurred in low-middle socio-demographic index (SDI) regions (EAPC=0.03, 95% CI 0.01 to 0.06). The number of deaths increased by 14.49% in low SDI regions and the ASMR increased in Southern Sub-Saharan Africa (EAPC=0.17, 95% CI 0.02 to 0.33). Negative correlations of EAPCs in ASIRs and ASMRs with SDI and universal health coverage index values in 2019 were detected at national levels.  Conclusions: Congenital birth defects are an important child health problem. There is urgent need to strengthen surveillance and detection of congenital birth defects, build and improve maternal and child healthcare capacity, and promote treatment and rehabilitation, especially in resource-limited countries. What is known: • Congenital birth defects were the fourth leading cause of death among children under 5 years in 2019, accounting for nearly 10% of deaths. What is new: • In this study using data from the Global Burden of Disease Study, global incident cases, deaths, and age-standardized mortality rate (ASMR) of congenital birth defects decreased, whereas age-standardized incidence rate (ASIR) remained stable from 1990 to 2019. • From 1990 to 2019, the most pronounced increase in ASIR occurred in Oceania, and the ASMR increased by an average of 0.17% per year in Southern Sub-Saharan Africa.

Analysis for trends in disease burden of congenital birth defects among children under 5 years old in China. / 中国5å²ä»¥ä¸‹å„¿ç«¥å ˆå¤©æ€§å‡ºç”Ÿç¼ºé™·çš„ç–¾ç— è´Ÿæ‹ è¶‹åŠ¿åˆ†æž.

OBJECTIVES: Congenital birth defects are the main source of disease burden among children under 5 years old in China. This study aims to compare the trends in disease burden of different congenital birth defects among Chinese children under 5 years old from 1990 to 2019, and to provide a scientific basis for strengthening the comprehensive prevention and control of birth defects. METHODS: Based on data from the Global Burden Disease (GBD) in 2019, the incidence mortality rate, and disability-adjusted life years (DALYs) rate of congenital birth defects among Chinese children under 5 years old from 1990 to 2019 were selected as evaluation indicators. The Joinpoint regression model was used to analyze the trends in disease burden of different types with congenital birth defects over three decades. The study also compared the differences in disease burden of congenital birth defects among children under 5 years old by gender. RESULTS: Compared to 1990, the DALYs rates of congenital heart anomalies (1 931.91/100 000), digestive congenital anomalies (364.63/100 000), neural tube defects (277.20/100 000), congenital musculoskeletal and limb anomalies (133.33/100 000), and Down syndrome (128.22/100 000) in children under 5 years old in China in 2019 were decreased 70.78%, 71.61%, 86.21%, 36.84% and 73.65%, respectively. From 1990 to 2019, the mortality rates and DALYs rates of different congenital birth defects showed an overall downward trend, but the incidence of digestive congenital anomalies and Down syndrome showed an upward trend after 2005 and 2001, respectively. Except for congenital musculoskeletal and limb anomalies, incidence of the remaining categories of birth defects were higher in boys than that in girls. CONCLUSIONS: The disease burden of congenital birth defects in children under 5 years old in China is decreased substantially from 1990 to 2019, but the burden of congenital heart anomalies is still serious and the incidence of some birth defect diseases is on the rise, and it is still crucial to strengthen the prevention and treatment for birth defects in children and propose targeted measures according to their gender characteristics.

Fertilization and neonatal outcomes after early rescue intracytoplasmic sperm injection: a retrospective analysis of 16,769 patients.

PURPOSE: To evaluate the efficacy and safety of short-term insemination and early-rescue intracytoplasmic sperm injection (ICSI), an approach that rescued oocytes with unclear second polar body 6 h after initial insemination by ICSI (early R-ICSI) to avoid total or near-total fertilization failure in conventional in vitro fertilization (IVF). METHODS: We performed a retrospective study in 16,769 patients (short-term IVF, n = 12,094; ICSI, n = 3452; early R-ICSI, n = 1223) who received IVF/ICSI treatment in our hospital from January 2009 to October 2018. Fertilization and clinical outcomes were compared among those three groups. RESULTS: When considering the R-ICSI embryos in the early R-ICSI group independently, the rates of fertilization and day-3 cleaved embryos in 2PN oocytes were comparable, the rates of fertilization (2PN) and high-quality embryos were lower, whereas the multi-PN fertilization rate (3.27%) was significantly higher than the ICSI group (1.26%). The difference of clinical pregnancy rate between the part of transferred R-ICSI embryos (40.81%) and the ICSI group (44.73%) remained nonsignificant. Furthermore, the rate of congenital birth defects in the early R-ICSI group (0.99%) was not significantly different from those in the short-term IVF (0.76%) and ICSI groups (1.07%). CONCLUSION: Despite the multi-PN fertilization rate, our study highlights early R-ICSI as a safe and effective alternative in assisted reproduction to decrease complete IVF fertilization failure and reduce ICSI utilization. Additional large amount and long-term follow-up studies are needed to further validate the use of early R-ICSI.

A deficiency in SUMOylation activity disrupts multiple pathways leading to neural tube and heart defects in Xenopus embryos.

BACKGROUND: Adenovirus protein, Gam1, triggers the proteolytic destruction of the E1 SUMO-activating enzyme. Microinjection of an empirically determined amount of Gam1 mRNA into one-cell Xenopus embryos can reduce SUMOylation activity to undetectable, but nonlethal, levels, enabling an examination of the role of this post-translational modification during early vertebrate development. RESULTS: We find that SUMOylation-deficient embryos consistently exhibit defects in neural tube and heart development. We have measured differences in gene expression between control and embryos injected with Gam1 mRNA at three developmental stages: early gastrula (immediately following the initiation of zygotic transcription), late gastrula (completion of the formation of the three primary germ layers), and early neurula (appearance of the neural plate). Although changes in gene expression are widespread and can be linked to many biological processes, three pathways, non-canonical Wnt/PCP, snail/twist, and Ets-1, are especially sensitive to the loss of SUMOylation activity and can largely account for the predominant phenotypes of Gam1 embryos. SUMOylation appears to generate different pools of a given transcription factor having different specificities with this post-translational modification involved in the regulation of more complex, as opposed to housekeeping, processes. CONCLUSIONS: We have identified changes in gene expression that underlie the neural tube and heart phenotypes resulting from depressed SUMOylation activity. Notably, these developmental defects correspond to the two most frequently occurring congenital birth defects in humans, strongly suggesting that perturbation of SUMOylation, either globally or of a specific protein, may frequently be the origin of these pathologies.

Multivitamin use and adverse birth outcomes in high-income countries: a systematic review and meta-analysis.

BACKGROUND: In high-income countries, a healthy diet is widely accessible. However, a change toward a poor-quality diet with a low nutritional value in high-income countries has led to an inadequate vitamin intake during pregnancy. OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the association between multivitamin use among women in high-income countries and the risk of adverse birth outcomes (preterm birth [primary outcome], low birthweight, small for gestational age, stillbirth, neonatal death, perinatal mortality, and congenital anomalies without further specification). STUDY DESIGN: We searched electronic databases (MEDLINE, Embase, Cochrane, Scopus, and CINAHL) from inception to June 17, 2016, using synonyms of pregnancy, study/trial type, and multivitamins. Eligible studies were all studies in high-income countries investigating the association between multivitamin use (3 or more vitamins or minerals in tablets or capsules) and adverse birth outcomes. We evaluated randomized, controlled trials using the Cochrane Collaboration tool. Observational studies were evaluated using the Newcastle-Ottawa Scale. Meta-analyses were applied on raw data for outcomes with data for at least 2 studies and were conducted using RevMan (version 5.3). Outcomes were pooled using the random-effect model. The quality of evidence was assessed using the Grades of Research, Assessment, Development and Evaluation approach. RESULTS: We identified 35 eligible studies including 98,926 women. None of the studies compared the use of folic acid and iron vs the use of multivitamins. The use of multivitamin did not change the risk of the primary outcome, preterm birth (relative risk, 0.84 [95% confidence interval, 0.69-1.03]). However, the risk of small for gestational age (relative risk, 0.77 [95% confidence interval, 0.63-0.93]), neural tube defects (relative risk, 0.67 [95% confidence interval, 0.52-0.87]), cardiovascular defects (relative risk, 0.83 [95% confidence interval, 0.70-0.98]), urine tract defects (relative risk, 0.60 [95% confidence interval, 0.46-0.78]), and limb deficiencies (relative risk, 0.68 [95% confidence interval, 0.52-0.89]) was decreased. Of the 35 identified studies, only 4 were randomized, controlled trials. The degree of clinical evidence according to the Grades of Research, Assessment, Development, and Evaluation system was low or very low for all outcomes except for recurrence of neural tube defects in which a moderate degree of clinical evidence was found. CONCLUSION: Routine multivitamin use in high-income countries can be recommended but with caution because of the low quality of evidence. Randomized, controlled trials or well-performed, large prospective cohort studies are needed.

Risk of selected structural abnormalities in infants after increased nuchal translucency measurement.

OBJECTIVE: We sought to examine the association between increased first-trimester fetal nuchal translucency (NT) measurement and major noncardiac structural birth defects in euploid infants. STUDY DESIGN: Included were 75,899 singleton infants without aneuploidy or critical congenital heart defects born in California in 2009 through 2010 with NT measured between 11-14 weeks of gestation. Logistic binomial regression was employed to estimate relative risks (RRs) and 95% confidence intervals (CIs) for occurrence of birth defects in infants with an increased NT measurement (by percentile at crown-rump length [CRL] and by ≥3.5 mm compared to those with measurements <90th percentile for CRL). RESULTS: When considered by CRL adjusted percentile and by measurement ≥3.5 mm, infants with a NT ≥95th percentile were at risk of having ≥1 major structural birth defects (any defect, RR, 1.6; 95% CI, 1.3-1.9; multiple defects, RR, 2.1; 95% CI, 1.3-3.4). Infants with a NT measurement ≥95th percentile were at particularly high risk for pulmonary, gastrointestinal, genitourinary, and musculoskeletal anomalies (RR, 1.6-2.7; 95% CI, 1.1-5.4). CONCLUSION: Our findings demonstrate that risks of major pulmonary, gastrointestinal, genitourinary, and musculoskeletal structural birth defects exist for NT measurements ≥95th percentile. The ≥3-fold risks were observed for congenital hydrocephalus; agenesis, hypoplasia, and dysplasia of the lung; atresia and stenosis of the small intestine; osteodystrophies; and diaphragm anomalies.

Epigenetic regulation of craniofacial development and disease.

BACKGROUND: The formation of the craniofacial complex relies on proper neural crest development. The gene regulatory networks (GRNs) and signaling pathways orchestrating this process have been extensively studied. These GRNs and signaling cascades are tightly regulated as alterations to any stage of neural crest development can lead to common congenital birth defects, including multiple syndromes affecting facial morphology as well as nonsyndromic facial defects, such as cleft lip with or without cleft palate. Epigenetic factors add a hierarchy to the regulation of transcriptional networks and influence the spatiotemporal activation or repression of specific gene regulatory cascades; however less is known about their exact mechanisms in controlling precise gene regulation. AIMS: In this review, we discuss the role of epigenetic factors during neural crest development, specifically during craniofacial development and how compromised activities of these regulators contribute to congenital defects that affect the craniofacial complex.

Global, regional and national burdens of reproduction-related congenital birth defects, 1990-2019.

Background: Reproduction-related congenital birth defects (RCBDs), including Klinefelter syndrome (KS), Turner syndrome (TS), and urogenital congenital anomalies (UCA), can lead to severe physical and psychosocial disorders. The global impact of RCBDs on children and adults is unknown, which limits high-quality development of populations and increases in life expectancy per capita. Methods: Annual incidence rates, prevalence rates (PR), and disability-adjusted life year (DALY) rates were collected for KS, TS, and UCA for 204 countries and territories, including at birth, for children younger than 1 year, and age-standardized (AS) for all ages. Linear regression was used to calculate their estimated annual percentage changes (EAPCs). Finally, the relationships between EAPCs of each indicator and sociodemographic index (SDI) was investigated using Pearson correlation analysis. Results: Globally, the age-standardized prevalence rate (ASPR) trend is decreasing in KS and TS and increasing in UCA. The DALY rates for children younger than 1 year were on a downward trend in KS and UCA, while they were still rising for TS. The AS-DALY rates were all on a downward trend in KS, TS, and UCA. The DALY rates of KS, TS and UCA were found higher in high-income countries in North America. In addition, the burdens of TS and UCA went down with increasing SDI, whereas the burden of KS increased with increasing SDI. Conclusion: The global burdens of RCBDs have decreased since 1990. This finding can help policymakers implement cost-effective interventions to reduce the burdens of RCBDs.

Maternal Cigarette Smoking and Congenital Upper and Lower Limb Differences: A Systematic Review and Meta-Analysis.

Maternal smoking during pregnancy has been associated with adverse effects on foetal development, including congenital limb anomalies. This systematic review aimed to provide an updated assessment of the association between maternal smoking during pregnancy and the risk of congenital limb anomalies. A systematic search was conducted to identify relevant studies published up to February 2023. Studies reporting on the relationship between maternal smoking during pregnancy and congenital digital anomalies or congenital limb reduction defects were included. Two independent reviewers screened the studies, extracted data, and assessed the quality of the included studies. Meta-analyses were performed to estimate the pooled odds ratios with 95% confidence intervals using fixed and random-effects models. In total, 37 publications comprising 11 cohort and 26 case-control studies were included in the systematic review. The meta-analysis demonstrated a significant increased risk of congenital limb reduction defects (pooled OR: 1.27, 95% CI: 1.18-1.38) in infants born to mothers who smoked during pregnancy. Similarly, a significant relationship was observed for the development of polydactyly/syndactyly/adactyly when considered as a single group (pooled OR: 1.32, 95% CI: 1.25-1.40). Yet, in contrast, no significant association was observed when polydactyly (pooled OR: 1.06, 95% CI: 0.88-1.27) or syndactyly (pooled OR: 0.91, 95% CI: 0.77-1.08) were considered individually. This systematic review provides updated evidence of a significant relationship between maternal smoking during pregnancy and increased risk of congenital limb anomalies. These findings highlight the potential detrimental effects of smoking on foetal limb development and underscore the importance of smoking cessation interventions for pregnant women to mitigate these risks.

The burden of congenital birth defects between 1990 and 2019 in China: an observational study.

Background: Congenital birth defects (CBDs) are a major public health issue. This study aims to assess trends in the burden of CBDs between 1990 and 2019 across China based on the Global Burden of Disease Study 2019 (GBD 2019). Methods: Indicators of the burden of CBDs included incidence, mortality, and disability-adjusted life years (DALYs). Metrics included number, rate, and age-standardized rate with 95% uncertainty intervals (UIs). Data were stratified by region [China, global, high-, middle-, low-socio-demographic index (SDI)], age, sex, and type of CBD. Average annual percentage changes (AAPC) and trends were evaluated. Results: In China, between 1990 and 2019, the age-standardized incidence rate for CBDs showed an increasing trend, with an AAPC of 0.26% (0.11% to 0.41%), reaching 148.12 per 105 person-years (124.03 to 176.33) in 2019. Most CBDs were congenital heart anomalies, with an AAPC of 0.12% (-0.08% to 0.32%). The age-standardized mortality rate for CBDs showed a decreasing trend, with an AAPC of -4.57% (-4.97% to -4.17%), reaching 4.62 per 105 person-years (3.88 to 5.57) in 2019. Most mortality was associated with congenital heart anomalies, with an AAPC of -3.77% (-4.35% to -3.19%). The age-standardized DALYs rate for CBDs showed a decreasing trend, with an AAPC of -3.74% (-3.95% to -3.52%), reaching 480.95 per 105 person-years (407.69 to 570.04) in 2019. Conclusions: Morbidity associated with CBDs increased in China between 1990 and 2019, accelerated by the adoption of the two-child policy, and ranked high globally. These findings emphasize the need for prenatal screening and primary and secondary prevention strategies.

Coffin-Siris syndrome: Clinical description of two cases.

Coffin-Siris syndrome is a rare disorder, which can be difficult to recognize. A broad spectrum of nonspecific clinical features is associated with Coffin-Siris syndrome, and the expression of these features is diverse. We describe two cases with Coffin-Siris syndrome with mutations in the ARID1A gene, with dissimilar presentation and clinical course.

Maternal and Neonatal Complications in Teen Pregnancies: A Comprehensive Study of 661,062 Patients.

PURPOSE: To provide a comprehensive assessment of maternal and neonatal complications associated with teen pregnancies in the United States. METHODS: Retrospective analysis of the Centers for Disease Control and Prevention natality live births database (2016-2019). Singleton births to women younger than 35 years from the following racial/ethnic groups were included: non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic. The risks of various complications were compared between teen patients (<20 years old) and nonteen patients (20-35 years old) using Pearson's chi-square test with the Bonferroni correction. Multivariate logistic regressions were used to adjust outcomes for potential confounders, including body mass index, race/ethnicity, payment method, prenatal care, parity, and the presence of chronic comorbidities. RESULTS: Teen pregnancies comprised approximately 6% of the study population (661,062 of 11,038,489). Teen pregnancies were associated with increased odds of several maternal complications, such as hypertensive disorders of pregnancy, eclampsia, preterm birth, blood transfusion, and chlamydial and gonorrheal infections. Teen pregnancies were also associated with increased odds of several neonatal complications, including congenital birth defects, low 5-minute Apgar score, suspected neonatal sepsis, and assisted ventilation. Conversely, teen pregnancies were associated with decreased odds of gestational diabetes, unplanned hysterectomy, macrosomia, low birth weight, and neonatal intensive care unit admission. DISCUSSION: Teen pregnancies in the United States are associated with increased risks of multiple adverse outcomes. This information should inform clinicians and policy makers about the unique risks of this highly vulnerable patient population and provide further knowledge for the important efforts to reduce teen birth rates in the United States.

Assisted Oocyte Activation With Calcium Ionophore Improves Pregnancy Outcomes and Offspring Safety in Infertile Patients: A Systematic Review and Meta-Analysis.

This study aimed to evaluate the efficacy and safety of calcium ionophore during assisted oocyte activation (AOA). This meta-analysis contained randomized controlled trials and prospective observational and retrospective trials. The summary odds ratio (OR) with 95% confidence intervals (CIs) was calculated for clinical pregnancy rate and live birth rate. Both fixed and random effects models were applied. A total of 22 studies were included into this meta-analysis. Seventeen of the included studies showed that calcium ionophore increased the clinical pregnancy rate (OR, 2.14; 95% CI, 1.38-3.31). Similarly, 14 studies indicated that AOA with calcium ionophore during intracytoplasmic sperm injection (ICSI) improved the live birth rate considerably (OR, 2.65; 95% CI, 1.53-4.60). Moreover, fertilization, blastocyst formation, and implantation rate were higher after using AOA with calcium ionophore combined with ICSI. In addition, calcium ionophore did not increase top-quality embryo rate, cleavage rate, miscarriage rate, congenital birth defects, and neonatal sex ratio. Therefore, calcium ionophore followed by ICSI not only significantly improved live birth and overall pregnancy, but also did not affect the incidence of miscarriage, congenital birth defects, and neonatal sex ratio. This meta-analysis indicated that using calcium ionophore to activate oocytes was beneficial for couples with poor fertilization rates following ICSI.

Diverse Fate of an Enigmatic Structure: 200 Years of Meckel's Cartilage.

Meckel's cartilage was first described by the German anatomist Johann Friedrich Meckel the Younger in 1820 from his analysis of human embryos. Two hundred years after its discovery this paper follows the development and largely transient nature of the mammalian Meckel's cartilage, and its role in jaw development. Meckel's cartilage acts as a jaw support during early development, and a template for the later forming jaw bones. In mammals, its anterior domain links the two arms of the dentary together at the symphysis while the posterior domain ossifies to form two of the three ear ossicles of the middle ear. In between, Meckel's cartilage transforms to a ligament or disappears, subsumed by the growing dentary bone. Several human syndromes have been linked, directly or indirectly, to abnormal Meckel's cartilage formation. Herein, the evolution, development and fate of the cartilage and its impact on jaw development is mapped. The review focuses on developmental and cellular processes that shed light on the mechanisms behind the different fates of this cartilage, examining the control of Meckel's cartilage patterning, initiation and maturation. Importantly, human disorders and mouse models with disrupted Meckel's cartilage development are highlighted, in order to understand how changes in this cartilage impact on later development of the dentary and the craniofacial complex as a whole. Finally, the relative roles of tissue interactions, apoptosis, autophagy, macrophages and clast cells in the removal process are discussed. Meckel's cartilage is a unique and enigmatic structure, the development and function of which is starting to be understood but many interesting questions still remain.

Reprogramming Axial Level Identity to Rescue Neural-Crest-Related Congenital Heart Defects.

The cardiac neural crest arises in the hindbrain, then migrates to the heart and contributes to critical structures, including the outflow tract septum. Chick cardiac crest ablation results in failure of this septation, phenocopying the human heart defect persistent truncus arteriosus (PTA), which trunk neural crest fails to rescue. Here, we probe the molecular mechanisms underlying the cardiac crest's unique potential. Transcriptional profiling identified cardiac-crest-specific transcription factors, with single-cell RNA sequencing revealing surprising heterogeneity, including an ectomesenchymal subpopulation within the early migrating population. Loss-of-function analyses uncovered a transcriptional subcircuit, comprised of Tgif1, Ets1, and Sox8, critical for cardiac neural crest and heart development. Importantly, ectopic expression of this subcircuit was sufficient to imbue trunk crest with the ability to rescue PTA after cardiac crest ablation. Together, our results reveal a transcriptional program sufficient to confer cardiac potential onto trunk neural crest cells, thus implicating new genes in cardiovascular birth defects.

Developing Practical Therapeutic Strategies that Target Protein SUMOylation.

Post-translational modification by small ubiquitin-like modifier (SUMO) has emerged as a global mechanism for the control and integration of a wide variety of biological processes through the regulation of protein activity, stability and intracellular localization. As SUMOylation is examined in greater detail, it has become clear that the process is at the root of several pathologies including heart, endocrine, and inflammatory disease, and various types of cancer. Moreover, it is certain that perturbation of this process, either globally or of a specific protein, accounts for many instances of congenital birth defects. In order to be successful, practical strategies to ameliorate conditions due to disruptions in this post-translational modification will need to consider the multiple components of the SUMOylation machinery and the extraordinary number of proteins that undergo this modification.

Analysis for trends in disease burden of congenital birth defects among children under 5 years old in China / 中南大学学报(医学版)

OBJECTIVES@#Congenital birth defects are the main source of disease burden among children under 5 years old in China. This study aims to compare the trends in disease burden of different congenital birth defects among Chinese children under 5 years old from 1990 to 2019, and to provide a scientific basis for strengthening the comprehensive prevention and control of birth defects.@*METHODS@#Based on data from the Global Burden Disease (GBD) in 2019, the incidence mortality rate, and disability-adjusted life years (DALYs) rate of congenital birth defects among Chinese children under 5 years old from 1990 to 2019 were selected as evaluation indicators. The Joinpoint regression model was used to analyze the trends in disease burden of different types with congenital birth defects over three decades. The study also compared the differences in disease burden of congenital birth defects among children under 5 years old by gender.@*RESULTS@#Compared to 1990, the DALYs rates of congenital heart anomalies (1 931.91/100 000), digestive congenital anomalies (364.63/100 000), neural tube defects (277.20/100 000), congenital musculoskeletal and limb anomalies (133.33/100 000), and Down syndrome (128.22/100 000) in children under 5 years old in China in 2019 were decreased 70.78%, 71.61%, 86.21%, 36.84% and 73.65%, respectively. From 1990 to 2019, the mortality rates and DALYs rates of different congenital birth defects showed an overall downward trend, but the incidence of digestive congenital anomalies and Down syndrome showed an upward trend after 2005 and 2001, respectively. Except for congenital musculoskeletal and limb anomalies, incidence of the remaining categories of birth defects were higher in boys than that in girls.@*CONCLUSIONS@#The disease burden of congenital birth defects in children under 5 years old in China is decreased substantially from 1990 to 2019, but the burden of congenital heart anomalies is still serious and the incidence of some birth defect diseases is on the rise, and it is still crucial to strengthen the prevention and treatment for birth defects in children and propose targeted measures according to their gender characteristics.

A new mammalian model system for thalidomide teratogenesis: Monodelphis domestica.

From 1957 to 1962, thalidomide caused birth defects in >10,000 children. While the drug was pulled from the market, thalidomide is currently prescribed to treat conditions including leprosy. As a result, a new generation of babies with thalidomide defects is being born in the developing world. This represents a serious problem, as the mechanisms by which thalidomide disrupts development remain unresolved. This lack of resolution is due, in part, to the absence of an appropriate mammalian model for thalidomide teratogenesis. We test the hypothesis that opossum (Monodelphis domestica) is well suited to model human thalidomide defects. Results suggest that opossum embryos exposed to thalidomide display a range of phenotypes (e.g., heart, craniofacial, limb defects) and penetrance similar to humans. Furthermore, all opossums with thalidomide defects exhibit vascular disruptions. Results therefore support the hypotheses that opossums make a good mammalian model for thalidomide teratogenesis, and that thalidomide can severely disrupt angiogenesis in mammals.

Current perspective of diethylstilbestrol (DES) exposure in mothers and offspring.

Diethylstilbestrol (DES) was an orally active estrogen prescribed to the pregnant women to prevent miscarriages. DES is known as a 'biological time bomb' and long-term effects of DES have been recorded in the mothers exposed to DES and their offspring (DES-daughters and DES-sons). Adverse pregnancy outcomes, infertility, cancer, and early menopause have been discovered in women exposed to DES, and some events occur in their offspring and subsequent generations. An increased risk of breast cancer is not limited to the DES-exposed daughters. There is an urgent need to find ways to stop the inheritance cycle of DES and prevent adverse effects of DES in the future generations. The present article reviews the health implications of DES exposure and screening exams currently recommended to DES daughters and their offspring.