There is little consistency in the use of instruments for measuring self-reported quality of life (QoL) in young children.
To systematically review studies of self-reported QoL in children aged <12 ...years with congenital health conditions, and to examine the agreement between self- and proxy-reports.
Literature databases (MEDLINE, EMBASE, Web of Science, PsychINFO) were systematically searched, reference lists of eligible studies were scanned.
We included studies published in English between January 1989 and June 2013 which used validated instruments to assess self-reported QoL in children aged <12 years with a distinct congenital health condition identified in early infancy.
We extracted data on study design, objective, sample characteristics, QoL assessment instrument, statistical techniques and results.
From 403 full-text articles assessed for eligibility, 50 studies underwent detailed review, and 37 were included in a narrative synthesis. Children's self-reported QoL was assessed by using a variety of generic and/or condition-specific instruments, with the Pediatric Quality of Life Inventory being the most frequently used (25% 9 studies). Regardless of the condition or the instrument used, children often reported QoL similar to the reference population, except for lower scores in the physical functioning/health domain. There were differences between younger and older age groups according to QoL domain. The child's perception of QoL differed from that of his or her parents, in particular for subjective domains such as emotional functioning, and these differences were age related. The main limitation of the review resulted from the lack of published studies on self-reported QoL in young children, in particular, lacking both self-reports and proxy reports. Existing studies demonstrated wide variability in the QoL instruments used and approaches to statistical analyses, lack of information about the formation of the study sample (response rate; comparison of responders and nonresponders) and low sample sizes in the age group of interest.
The reviewed studies demonstrated that, even for younger children, both child and parent perspectives are essential to understanding the impact of a condition on a child's QoL.
This systematic review and meta-analysis was aimed at determining whether paternal age is a risk factor for offspring birth defects.
A total of 38 and 11 studies were included in the systematic ...review and meta-analysis, respectively. Compared with reference, fathers aged 25 to 29, young fathers (< 20 years) could increase the risk of urogenital abnormalities (OR: 1.50, 95 % CI: 1.03-2.19) and chromosome disorders (OR: 1.38, 95 % CI: 1.12-1.52) in their offsprings; old fathers (≥ 40 years) could increase the risk of cardiovascular abnormalities (OR: 1.10, 95 % CI: 1.01-1.20), facial deformities (OR: 1.08, 95 % CI: 1.00-1.17), urogenital abnormalities (OR: 1.28, 95 % CI: 1.07-1.52), and chromosome disorders (OR: 1.30, 95 % CI: 1.12-1.52).
Our study indicated that paternal age is associated with a moderate increase in the incidence of urogenital and cardiovascular abnormalities, facial deformities, and chromosome disorders.
PubMed, Web of Science, the Cochrane Library, and Embase were searched for relevant literatures from 1960 to February 2020. The systematic review follows PRISMA guidelines. Relevant meta-analyses were performed.
Gene expression often requires interaction between promoters and distant enhancers, which occur within the context of highly organized topologically associating domains (TADs). Using a series of ...engineered chromosomal rearrangements at the Shh locus, we carried out an extensive fine-scale characterization of the factors that govern the long-range regulatory interactions controlling Shh expression. We show that Shh enhancers act pervasively, yet not uniformly, throughout the TAD. Importantly, changing intra-TAD distances had no impact on Shh expression. In contrast, inversions disrupting the TAD altered global folding of the region and prevented regulatory contacts in a distance-dependent manner. Our data indicate that the Shh TAD promotes distance-independent contacts between distant regions that would otherwise interact only sporadically, enabling functional communication between them. In large genomes where genomic distances per se can limit regulatory interactions, this function of TADs could be as essential for gene expression as the formation of insulated neighborhoods.
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•Potential for responsiveness to Shh enhancers correlates with contact frequency•Changing distances within Shh TAD has little effect on Shh expression•Inversions bridging the Shh TAD boundaries disrupt folding and regulatory contacts•Decreasing genomic distance can rescue disrupted long-range regulatory interactions
Using systematic genomic rearrangements at the Shh locus, Symmons et al. demonstrate that the topologically associating domain overlapping the locus acts as a functional regulatory mold by promoting contacts between elements that would otherwise be too rare to yield a functional outcome due to the dampening effects of large genomic distances.
Introduction
Several studies have reported on the maternal age‐associated risks of congenital anomalies. However, there is a paucity of studies with comprehensive review of anomalies. We aimed to ...quantify the risk of birth defects in children born to middle‐aged mothers compared with that in children born to young or older mothers.
Material and methods
We classified maternal ages into three groups: young (<20 years old), middle (20–34 years old) and older age (≥35 years old). Observational studies that met our age criteria were eligible for inclusion. The articles searched using the Embase and MEDLINE databases were those published from 1989 to January 21, 2021. The Newcastle–Ottawa scale was used to assess the risk of bias. If heterogeneity exceeded 50%, the random effect method was used; otherwise, the fixed‐effect method was used. Prospero registration number: CRD42021235229.
Results
We included 15 cohort, 14 case–control and 36 cross‐sectional studies. The pooled unadjusted odds ratio (95% CI) of any congenital anomaly was 1.64 (1.40–1.92) and 1.05 (0.95–1.15) in the older and young age groups, respectively (very low quality of evidence). The pooled unadjusted odds ratio of chromosomal anomaly was 5.64 (5.13–6.20) and 0.69 (0.54–0.88) in the older and young age groups, respectively. The pooled unadjusted odds ratio of non‐chromosomal anomaly was 1.09 (1.01–1.17) and 1.10 (1.01–1.21) in the older and young age groups, respectively (very low quality of evidence). The incidence of abdominal wall defects was increased in children of women in the young maternal age group.
Conclusions
We identified that very low quality evidence suggests that women in the older maternal age group had increased odds of having children with congenital anomalies compared with those in the 20–34 year age group. There was no increase in odds of children with congenital anomalies in women of <20 year age group except for abdominal defects compared with those in the 20–34 year age group. The results stem from very low quality evidence with no adjustment of confounders.
Microglia are CNS-resident macrophages that scavenge debris and regulate immune responses. Proliferation and development of macrophages, including microglia, requires Colony Stimulating Factor 1 ...Receptor (CSF1R), a gene previously associated with a dominant adult-onset neurological condition (adult-onset leukoencephalopathy with axonal spheroids and pigmented glia). Here, we report two unrelated individuals with homozygous CSF1R mutations whose presentation was distinct from ALSP. Post-mortem examination of an individual with a homozygous splice mutation (c.1754−1G>C) demonstrated several structural brain anomalies, including agenesis of corpus callosum. Immunostaining demonstrated almost complete absence of microglia within this brain, suggesting that it developed in the absence of microglia. The second individual had a homozygous missense mutation (c.1929C>A p.His643Gln) and presented with developmental delay and epilepsy in childhood. We analyzed a zebrafish model (csf1rDM) lacking Csf1r function and found that their brains also lacked microglia and had reduced levels of CUX1, a neuronal transcription factor. CUX1+ neurons were also reduced in sections of homozygous CSF1R mutant human brain, identifying an evolutionarily conserved role for CSF1R signaling in production or maintenance of CUX1+ neurons. Since a large fraction of CUX1+ neurons project callosal axons, we speculate that microglia deficiency may contribute to agenesis of the corpus callosum via reduction in CUX1+ neurons. Our results suggest that CSF1R is required for human brain development and establish the csf1rDM fish as a model for microgliopathies. In addition, our results exemplify an under-recognized form of phenotypic expansion, in which genes associated with well-recognized, dominant conditions produce different phenotypes when biallelically mutated.
Objective To evaluate the incidence of brain injury after neonatal surgery for noncardiac congenital anomalies using magnetic resonance imaging (MRI). Study design An MRI was obtained in 101 infants ...at 7 days range: 1-115 after neonatal surgery for major noncardiac congenital anomalies. Brain injury was assessed using T1, T2, diffusion weighted imaging, and susceptibility-weighted imaging. Results Thirty-two preterm infants (<37 weeks of gestation) and 69 full-term infants were included. MRI abnormalities were found in 24 (75%) preterm and 40 (58%) full-term infants. Parenchymal lesions were noted in 23 preterm (72%) and 29 full-term infants (42%). These consisted of punctate white matter lesions (n = 45), punctate cerebellar lesions (n = 17), thalamic infarction (n = 5), and periventricular hemorrhagic infarction (n = 4). Nonparenchymal abnormalities were found in 9 (28%) preterm and 26 (38%) full-term infants. These included supra- and infratentorial subdural hemorrhages (n = 30), intraventricular hemorrhage grade II (n = 7), and asymptomatic sinovenous thrombosis (n = 1). A combination of parenchymal lesions was present in 21 infants. Of infants who had an MRI within 10 days after surgery, punctate white matter lesions were visible on diffusion weighted imaging in 22 (61%), suggestive of recent ischemic origin. Type of congenital anomaly and prematurity were most predictive of brain injury. Conclusions Infants who have neonatal surgery for noncardiac congenital anomalies are at risk of brain injury, potentially accounting for the neurodevelopmental delay frequently observed in this population. Further research is warranted into potential mechanisms of brain injury and its timing of onset. Long-term neurodevelopmental follow-up is needed in this vulnerable population.
Purpose The objective of this study was to examine the associations between paternal age and birth defects of unknown etiologies while carefully controlling for maternal age. Methods By using 1997 to ...2004 data from the National Birth Defects Prevention Study, we fit logistic regression models with paternal and maternal age as continuous variables while adjusting for demographic and other factors. Results Elevated odds ratios (ORs) for each year increase in paternal age were found for cleft palate (OR. 1.02, 95% confidence interval 95% CI, 1.00–1.04), diaphragmatic hernia (OR, 1.04; 95% CI, 1.02–1.06), right ventricular outflow tract obstruction (OR, 1.03; 95% CI, 1.01–1.04), and pulmonary valve stenosis (OR, 1.02, 95% CI, 1.01–1.04). At younger paternal ages, each year increase in paternal age correlated with increased odds of having offspring with encephalocele, cataract, esophageal atresia, anomalous pulmonary venous return, and coarctation of the aorta, but these increased odds were not observed at older paternal ages. The effect of paternal age was modified by maternal age for gastroschisis, omphalocele, spina bifida, all orofacial clefts, and septal heart defects. Conclusions Our findings suggest that paternal age may be a risk factor for some multifactorial birth defects.
Zika virus was recently linked to birth defects, especially microcephaly. In this report from French territories in the Americas, the rate of birth defects possibly associated with intrapartum Zika ...virus infection was found to be 7%.
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