Canine congenital malformations are structural or functional abnormalities of organs present at birth that possibly interfere with the viability of newborns, thus contributing to neonatal mortality. ...This study evaluated and described the incidence of congenital malformations in neonatal dogs and determined the mortality rates among those affected. Of the 178 litters and 803 newborns included in the study, 24.7% (44/178) of the litters presented neonates with congenital malformations. The total rate of neonates that presented malformations was 6.7% (64/803). The total mortality rate in newborns with congenital defects was 5.4% (44/803), representing 68.7% (44/64) of the deaths observed among those affected. The early (0–2 days old) and late (3–30 days old) mortality rates among the affected neonates were 61.4% (27/44) and 38.6% (17/44), respectively. In total, 27 malformations were recorded, and the most common congenital defects were cleft palate 2.8% (23/803) and hydrocephaly 1.5% (12/803), either alone or associated with other malformations. The malformations were recorded in 15 breeds: Pug, Miniature Pinscher, Rottweiler, Pitbull, French Bulldog, English Bulldog, Dachshund, Labrador Retriever, Lhasa Apso, Poodle, German Spitz, Yorkshire Terrier, Shih-tzu, Brazilian Terrier and mixed breed. One case of exposure to a teratogenic agent was reported, but no maternal exposure to teratogens during gestation was reported with the other litters. The occurrence of congenital defects may be related to genetic factors since the highest incidence of malformations (84.4%) was observed in purebred dogs.
Innovations in epitranscriptomics have resulted in the identification of more than 160 RNA modifications to date. These developments, together with the recent discovery of writers, readers, and ...erasers of modifications occurring across a wide range of RNAs and tissue types, have led to a surge in integrative approaches for transcriptome-wide mapping of modifications and protein–RNA interaction profiles of epitranscriptome players. RNA modification maps and crosstalk between them have begun to elucidate the role of modifications as signaling switches, entertaining the notion of an epitranscriptomic code as a driver of the post-transcriptional fate of RNA. Emerging single-molecule sequencing technologies and development of antibodies specific to various RNA modifications could enable charting of transcript-specific epitranscriptomic marks across cell types and their alterations in disease.
A literature survey on RNA modifications reveals that RNA modifications are abundant in tRNAs, rRNAs, snoRNAs, and snRNAs but that their diversity is prominent in tRNAs, rRNAs, and mRNAs followed by snRNAs and snoRNAs.
Increasing evidence provides a link between RNA modifications and post-transcriptional regulatory processes.
Gene knockout and functional studies report the importance of RNA modifications in human health and disease.
Emerging long read direct RNA sequencing technologies and development of antibodies specific to RNA modifications could be promising venues for charting the combinatorial epitranscriptomic code across cell types.
Locus- and cell-type-specific combinations of epitranscriptome marks could drive the post-transcriptional regulatory fate of an RNA molecule.
Some maternal infections, contracted before or during pregnancy, can be transmitted to the fetus, during gestation (congenital infection), during labor and childbirth (perinatal infection) and ...through breastfeeding (postnatal infection). The agents responsible for these infections can be viruses, bacteria, protozoa, fungi. Among the viruses most frequently responsible for congenital infections are Cytomegalovirus (CMV), Herpes simplex 1–2, Herpes virus 6, Varicella zoster. Moreover Hepatitis B and C virus, HIV, Parvovirus B19 and non-polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth. Recently, new viruses have emerged, SARS-Cov-2 and Zika virus, of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy.
Viral infections in pregnancy can damage the fetus (spontaneous abortion, fetal death, intrauterine growth retardation) or the newborn (congenital anomalies, organ diseases with sequelae of different severity). Some risk factors specifically influence the incidence of transmission to the fetus: the timing of the infection in pregnancy, the order of the infection, primary or reinfection or chronic, the duration of membrane rupture, type of delivery, socio-economic conditions and breastfeeding. Frequently infected neonates, symptomatic at birth, have worse outcomes than asymptomatic. Many asymptomatic babies develop long term neurosensory outcomes.
The way in which the virus interacts with the maternal immune system, the maternal-fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal‑neonatal outcomes of maternal infections. The maternal immune system undergoes functional adaptation during pregnancy, once thought as physiological immunosuppression. This adaptation, crucial for generating a balance between maternal immunity and fetus, is necessary to promote and support the pregnancy itself and the growth of the fetus. When this adaptation is upset by the viral infection, the balance is broken, and the infection can spread and lead to the adverse outcomes previously described. In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn.
•Prevention of congenital viral infections starts during prenatal pathways.•Diagnosis of congenital infection allows prenatal treatment for some infections.•Prenatal treatment of some infections could improve neonatal outcomes.•Long-term follow-up of congenitally infected neonates is required.
Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth cohort 2010-2014.
Data from 39 ...U.S. population-based birth defects surveillance programs (16 active case-finding, 10 passive case-finding with case confirmation, and 13 passive without case confirmation) were used to calculate pooled prevalence estimates for major defects by case-finding approach. Fourteen active case-finding programs including at least live birth and stillbirth pregnancy outcomes monitoring approximately one million births annually were used to develop national prevalence estimates, adjusted for maternal race/ethnicity (for all conditions examined) and maternal age (trisomies and gastroschisis). These calculations used a similar methodology to the previous estimates to examine changes over time.
The adjusted national birth prevalence estimates per 10,000 live births ranged from 0.62 for interrupted aortic arch to 16.87 for clubfoot, and 19.93 for the 12 critical congenital heart defects combined. While the birth prevalence of most birth defects studied remained relatively stable over 15 years, an increasing prevalence was observed for gastroschisis and Down syndrome. Additionally, the prevalence for atrioventricular septal defect, tetralogy of Fallot, omphalocele, and trisomy 18 increased in this period compared to the previous periods. Active case-finding programs generally had higher prevalence rates for most defects examined, most notably for anencephaly, anophthalmia/microphthalmia, trisomy 13, and trisomy 18.
National estimates of birth defects prevalence provide data for monitoring trends and understanding the impact of these conditions. Increasing prevalence rates observed for selected conditions warrant further examination.
The true incidence of congenital anomalies in sub-Saharan Africa is unknown. Owing to complex challenges associated with congenital anomalies, many affected babies may never present to a health ...facility, resulting in an underestimation of disease burden.
Interviews were conducted with Ugandans between September 2018 and May 2019. Responses from community members versus families of children with congenital anomalies were compared.
A total of 198 Ugandans were interviewed (91 family members, 80 community members). All participants (N = 198) believed that seeking surgical care would lead to poverty, 43% (n = 84) assumed fathers would abandon the child, and 26% (n = 45) thought a child with a congenital anomaly in their community had been left to die. Causes of anomalies were believed to be contraceptive methods (48%, n = 95), witchcraft (17%, n = 34), or drugs (10%, n = 19). Of family members, 25 (28%) were advised to allow the child to die. Families with affected children were more likely to have a lower income (P < .001), believe anomalies could be treated (P = .007), but thought that allowing the child to die was best for the family (32% vs 9%; P < .0001). Monthly household income <50,000 Uganda shillings ($13 United States dollars) was a significant predictor of the father leaving the family (P = .024), being advised to not pursue medical care (P = .046), and believing that God should decide the child’s fate (P = .047).
Families face significant financial and social pressures when deciding to seek surgical care for a child with a congenital anomaly. Many children with anomalies may die and never reach a health facility to be counted, thus contributing to a hidden mortality.
The appropriate management of asymptomatic congenital pulmonary malformations (CPMs) remains controversial. Prophylactic surgery is recommended to avoid the risk for development of pulmonary ...infections and to prevent the highly debated development of malignancy. However, the true risk for development of malignancy remains unknown. A systematic review analyzed all cases in which lung tumors associated with CPMs in both the pediatric and adult populations were described.
A comprehensive literature search was carried out; it included all the cases in which an association between CPMs and malignant pulmonary lesions was reported.
In all, 134 publications were eligible for inclusion. In 168 patients CPM was found associated with lung tumor. The diagnosis was made in 76 children at a mean age of 3.68 ± 3.4, whereas in the adult population (n = 92) it was made at a mean age of 44.62 ± 16.09. Cough was the most frequent presenting symptom both in children and in adults. Most of the patients underwent lobectomy. The tumor most often associated with CPM was pleuropulmonary bastoma in children (n = 31) and adenocarcinoma (n = 20) or bronchioloalveolar carcinoma (n = 20) in adults. The CPM most frequenty associated with tumors in children was congenital cystic adenomatoid malformation (n = 37), especially type 1 (n = 21), whereas in adults it was bronchogenic cyst (n = 25), followed by congenital cystic adenomatoid malformation (n = 21).
CPMs should be followed up and never underestimated because they may conceal a tumor. Apparently, there is no age limit for malignant progression of CPMs and no limit of the interval between first detection of the CPM and appearance of the associated tumor.
IMPORTANCE: Understanding the risk of birth defects associated with Zika virus infection during pregnancy may help guide communication, prevention, and planning efforts. In the absence of Zika virus, ...microcephaly occurs in approximately 7 per 10 000 live births. OBJECTIVE: To estimate the preliminary proportion of fetuses or infants with birth defects after maternal Zika virus infection by trimester of infection and maternal symptoms. DESIGN, SETTING, AND PARTICIPANTS: Completed pregnancies with maternal, fetal, or infant laboratory evidence of possible recent Zika virus infection and outcomes reported in the continental United States and Hawaii from January 15 to September 22, 2016, in the US Zika Pregnancy Registry, a collaboration between the CDC and state and local health departments. EXPOSURES: Laboratory evidence of possible recent Zika virus infection in a maternal, placental, fetal, or infant sample. MAIN OUTCOMES AND MEASURES: Birth defects potentially Zika associated: brain abnormalities with or without microcephaly, neural tube defects and other early brain malformations, eye abnormalities, and other central nervous system consequences. RESULTS: Among 442 completed pregnancies in women (median age, 28 years; range, 15-50 years) with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 (6%; 95% CI, 4%-8%) fetuses or infants. There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%; 95% CI, 4%-9%) pregnant asymptomatic women and 10 of 167 (6%; 95% CI, 3%-11%) symptomatic pregnant women. Of the 26 affected fetuses or infants, 4 had microcephaly and no reported neuroimaging, 14 had microcephaly and brain abnormalities, and 4 had brain abnormalities without microcephaly; reported brain abnormalities included intracranial calcifications, corpus callosum abnormalities, abnormal cortical formation, cerebral atrophy, ventriculomegaly, hydrocephaly, and cerebellar abnormalities. Infants with microcephaly (18/442) represent 4% of completed pregnancies. Birth defects were reported in 9 of 85 (11%; 95% CI, 6%-19%) completed pregnancies with maternal symptoms or exposure exclusively in the first trimester (or first trimester and periconceptional period), with no reports of birth defects among fetuses or infants with prenatal exposure to Zika virus infection only in the second or third trimesters. CONCLUSIONS AND RELEVANCE: Among pregnant women in the United States with completed pregnancies and laboratory evidence of possible recent Zika infection, 6% of fetuses or infants had evidence of Zika-associated birth defects, primarily brain abnormalities and microcephaly, whereas among women with first-trimester Zika infection, 11% of fetuses or infants had evidence of Zika-associated birth defects. These findings support the importance of screening pregnant women for Zika virus exposure.
•Advanced maternal age increases chromosome segregation errors during meiosis.•Recombination failure and cohesin degradation promote chromosome mis-segregation.•Older oocytes have reduced expression ...of core SAC components.•Mitochondrial dysfunction contributes to reduced oocyte quality.•Dietary intervention may mitigate the effect of maternal aging on oocyte quality.
It is well established that maternal age is associated with a rapid decline in the production of healthy and high-quality oocytes resulting in reduced fertility in women older than 35 years of age. In particular, chromosome segregation errors during meiotic divisions are increasingly common and lead to the production of oocytes with an incorrect number of chromosomes, a condition known as aneuploidy. When an aneuploid oocyte is fertilized by a sperm it gives rise to an aneuploid embryo that, except in rare situations, will result in a spontaneous abortion. As females advance in age, they are at higher risk of infertility, miscarriage, or having a pregnancy affected by congenital birth defects such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Turner syndrome (monosomy X). Here, we review the potential molecular mechanisms associated with increased chromosome segregation errors during meiosis as a function of maternal age. Our review shows that multiple exogenous and endogenous factors contribute to the age-related increase in oocyte aneuploidy. Specifically, the weight of evidence indicates that recombination failure, cohesin deterioration, spindle assembly checkpoint (SAC) disregulation, abnormalities in post-translational modification of histones and tubulin, and mitochondrial dysfunction are the leading causes of oocyte aneuploidy associated with maternal aging. There is also growing evidence that dietary and other bioactive interventions may mitigate the effect of maternal aging on oocyte quality and oocyte aneuploidy, thereby improving fertility outcomes. Maternal age is a major concern for aneuploidy and genetic disorders in the offspring in the context of an increasing proportion of mothers having children at increasingly older ages. A better understanding of the mechanisms associated with maternal aging leading to aneuploidy and of intervention strategies that may mitigate these detrimental effects and reduce its occurrence are essential for preventing abnormal reproductive outcomes in the human population.
Summary Background Congenital anomalies are a leading cause of infant death and disability and their incidence varies between ethnic groups in the UK. Rates of infant death are highest in children of ...Pakistani origin, and congenital anomalies are the most common cause of death in children younger than 12 in this ethnic group. We investigated the incidence of congenital anomalies in a large multiethnic birth cohort to identify the causes of the excess of congenital anomalies in this community. Methods We obtained questionnaire data from the mothers of children with one or more anomalies from the Born in Bradford study, a prospective birth cohort study of 13 776 babies and their families in which recruitment was undertaken between 2007 and 2011. Details of anomalies were prospectively reported to the study and we cross checked these details against medical records. We linked data for anomalies to maternal questionnaire and clinical data gathered as part of the Born in Bradford study. We calculated univariate and multivariate risk ratios (RRs) with 95% CIs for various maternal risk factors. Findings Of 11 396 babies for whom questionnaire data were available, 386 (3%) had a congenital anomaly. Rates for congenital anomaly were 305·74 per 10 000 livebirths, compared with a national rate of 165·90 per 10 000. The risk was greater for mothers of Pakistani origin than for those of white British origin (univariate RR 1·96, 95% CI 1·56–2·46). Overall, 2013 (18%) babies were the offspring of first-cousin unions. These babies were mainly of Pakistani origin—1922 (37%) of 5127 babies of Pakistani origin had parents in first-cousin unions. Consanguinity was associated with a doubling of risk for congenital anomaly (multivariate RR 2·19, 95% CI 1·67–2·85); we noted no association with increasing deprivation. 31% of all anomalies in children of Pakistani origin could be attributed to consanguinity. We noted a similar increase in risk for mothers of white British origin older than 34 years (multivariate RR 1·83, 95% CI 1·14–3·00). Maternal education to degree level was protective (0·53, 95% CI 0·38–0·75), irrespective of ethnic origin. Interpretation Consanguinity is a major risk factor for congenital anomaly. The risk remains even after adjustment for deprivation, and accounts for almost a third of anomalies in babies of Pakistani origin. High levels of educational attainment are associated with reduced risk in all ethnic groups. Our findings will be valuable in health promotion and public health, and to those commissioning antenatal, paediatric, and clinical genetic services. Sensitive advice about the risks should be provided to communities at increased risk, and to couples in consanguineous unions, to assist in reproductive decision making. Funding National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care programme.
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