Incidence, risk factors, and outcomes of preterm and early term births : a population-based register study

Preterm birth (PTB) and early term birth (ETB) are associated with high risks of perinatal mortality and morbidity. While extreme to very PTBs have been extensively studied, studies on infants born at later stages of pregnancy, particularly late PTBs and ETBs, are lacking. In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes of PTB and ETB births in Qatar. We examined 15,865 singleton live births using 12-month retrospective registry data from the PEARL-Peristat Study. PTB and ETB incidence rates were 8.8% and 33.7%, respectively. PTB and ETB in-hospital mortality rates were 16.9% and 0.2%, respectively. Advanced maternal age, pre-gestational diabetes mellitus (PGDM), assisted pregnancies, and preterm history independently predicted both PTB and ETB, whereas chromosomal and congenital abnormalities were found to be independent predictors of PTB but not ETB. All groups of PTB and ETB were significantly associated with low birth weight (LBW), large for gestational age (LGA) births, caesarean delivery, and neonatal intensive care unit (NICU)/or death of neonate in labor room (LR)/operation theatre (OT). On the other hand, all or some groups of PTB were significantly associated with small for gestational age (SGA) births, Apgar 7 at 1 and 5 minutes and in-hospital mortality. The findings of this study may serve as a basis for taking better clinical decisions with accurate assessment of risk factors, complications, and predictions of PTB and ETB

Incidence, risk factors, and feto-maternal outcomes of inappropriate birth weight for gestational age among singleton live births in Qatar : a population-based study

Background Abnormal fetal growth can be associated with factors during pregnancy and at postpartum. Objective In this study, we aimed to assess the incidence, risk factors, and feto-maternal outcomes associated with small-for-gestational age (SGA) and large-for-gestational age (LGA) infants. Methods We performed a population-based retrospective study on 14,641 singleton live births registered in the PEARL-Peristat Study between April 2017 and March 2018 in Qatar. We estimated the incidence and examined the risk factors and outcomes using univariate and multivariate analysis. Results SGA and LGA incidence rates were 6.0% and 15.6%, respectively. In-hospital mortality among SGA and LGA infants was 2.5% and 0.3%, respectively, while for NICU admission or death in labor room and operation theatre was 28.9% and 14.9% respectively. Preterm babies were more likely to be born SGA (aRR, 2.31; 95% CI, 1.45–3.57) but male infants (aRR, 0.57; 95% CI, 0.4–0.81), those born to parous (aRR 0.66; 95% CI, 0.45–0.93), or overweight (aRR, 0.64; 95% CI, 0.42–0.97) mothers were less likely to be born SGA. On the other hand, males (aRR, 1.82; 95% CI, 1.49–2.19), infants born to parous mothers (aRR 2.16; 95% CI, 1.63–2.82), or to mothers with gestational diabetes mellitus (aRR 1.36; 95% CI, 1.11–1.66), or pre-gestational diabetes mellitus (aRR 2.58; 95% CI, 1.8–3.47) were significantly more likely to be LGA. SGA infants were at high risk of in-hospital mortality (aRR, 226.56; 95% CI, 3.47–318.22), neonatal intensive care unit admission or death in labor room or operation theatre (aRR, 2.14 (1.36–3.22). Conclusion Monitoring should be coordinated to alleviate the risks of inappropriate fetal growth and the associated adverse consequences.The PEARL-Peristat study was funded by Qatar National Research Fund (Grant no NPRP 6-238-3-059) and was sponsored by the Medical Research Centre, Hamad Medical Corporation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Management of chronic myeloid leukaemia : current treatment options, challenges, and future strategies

Small molecule therapy is a critical component of targeted anticancer treatment, with tyrosine kinase inhibitors (TKIs) being the first compounds to treat the clonal Chronic Myelogenous Leukaemia (CML) translocation t (9;22) (q34; q11) effectively since 2001. TKIs, such as imatinib, have improved the 10-year survival rate of CML patients to 80%. They bind the kinase and inhibit downstream signaling pathways. However, therapy failure may be seen in 20-25% of CML patients due to intolerance or inadequacy related to dependent or independent mechanisms. This review aimed to summarize current treatment options involving TKIs, resistance mechanisms and the prospective approaches to overcome TKI resistance. We highlight -dependent mechanisms of TKI resistance by reviewing clinically-documented mutations and their consequences for TKI binding. In addition, we summarize independent pathways, including the relevance of drug efflux, dysregulation of microRNA, and the involvement of alternative signaling pathways. We also discuss future approaches, such as gene-editing techniques in the context of CML, as potential therapeutic strategies

Prevalence, predictors, and outcomes of major congenital anomalies : a population-based register study

Congenital anomalies (CAs) are a leading cause of morbidity and mortality in early life. We aimed to assess the incidence, risk factors, and outcomes of major CAs in the State of Qatar. A population-based retrospective data analysis of registry data retrieved from the Perinatal Neonatal Outcomes Research Study in the Arabian Gulf (PEARL-Peristat Study) between April 2017 and March 2018. The sample included 25,204 newborn records, which were audited between April 2017 and March 2018, of which 25,073 live births were identified and included in the study. Maternal risk factors and neonatal outcomes were assessed for association with specific CAs, including chromosomal/genetic, central nervous system (CNS), cardiovascular system (CVS), facial, renal, multiple congenital anomalies (MCAs) using univariate and multivariate analyses. The incidence of any CA among live births was 1.3% (n = 332). The most common CAs were CVS (n = 117; 35%), MCAs (n = 69, 21%), chromosomal/genetic (51; 15%), renal (n = 39; 12%), CNS (n = 20; 6%), facial (14, 4%), and other (GIT, Resp, Urogenital, Skeletal) (n = 22, 7%) anomalies. Multivariable regression analysis showed that multiple pregnancies, parity ≥ 1, maternal BMI, and demographic factors (mother’s age and ethnicity, and infant’s gender) were associated with various specific CAs. In-hospital mortality rate due to CAs was estimated to be 15.4%. CAs were significantly associated with high rates of caesarean deliveries (aOR 1.51; 95% CI 1.04–2.19), Apgar < 7 at 1 min (aOR 5.44; 95% CI 3.10–9.55), Apgar < 7 at 5 min (aOR 17.26; 95% CI 6.31–47.18), in-hospital mortality (aOR 76.16; 37.96–152.8), admission to neonatal intensive care unit (NICU) or perinatal death of neonate in labor room (LR)/operation theatre (OT) (aOR 34.03; 95% CI 20.51–56.46), prematurity (aOR 4.17; 95% CI 2.75–6.32), and low birth weight (aOR 5.88; 95% CI 3.92–8.82) before and after adjustment for the significant risk factors. This is the first study to assess the incidence, maternal risk factors, and neonatal outcomes associated with CAs in the state of Qatar. Therefore, a specialized congenital anomaly data registry is needed to identify risk factors and outcomes. In addition, counselling of mothers and their families may help to identify specific needs for pregnant women and their babies.Open Access funding provided by the Qatar National Library. The PEARL-Peristat study was funded by Qatar National Research Fund (Grant no NPRP 6-238-3-059) and was sponsored by the Medical Research Centre, Hamad Medical Corporation.Scopu

Studying Frequencies, Types and Causes of Medical Laboratory Associated Errors Using the Electronic Occurrence, Variance and Accident (OVA) Reporting System in Department of Laboratory Medicine and Pathology at Hamad Medical Corporation (HMC)

Medical laboratory services are an integral part of healthcare systems that play significant roles in over 70% of medical decisions. Thus, unintentional errors that occur during total testing process (TTP) of laboratory may cause adverse outcomes. Therefore, implementing a system that assists healthcare professional to collect, track and analyze the frequency of incidents is essential for quality improvement. Hamad Medical Corporation (HMC) has implemented OVA system for reporting occurrences, variances and accidents (OVA). Objectives: This study was conducted to (i) determine the types of laboratory associated errors and (ii) to analyze the frequencies and causes of these errors. Design and Methods: The present study, a descriptive retrospective investigation, analyzed 38,814 OVA incidents. The laboratory quality management department provided the incidents recorded by the laboratory information system (LIS) for a three years period from first of January 2017 up to thirty first of December 2019. Incident types were classified into three categories: preanalytical, analytical, post analytical. Descriptive statistical analysis was performed by Microsoft Excel office 365, and frequencies as well as the percentages of incidents were determined. Results: Out of the 38,814 OVA reports, 18,679 (47.6%), 15,347 (40.0%), 4788 (12.4%) incidents occurred in 2017, 2018 and 2019 respectively. The events were grouped into three categories showing 95% for preanalytical, 2% for analytical and 3% for postanalytical categories. The data showed that 91.7% of sample rejection in preanalytical category were due to clotted, hemolysis, and insufficient patient sample volume. In analytical category, quality control issues and equipment errors represent about 82.8% and 17.2% respectively. Finally, most of postanalytical errors were delay in critical results 50.4% and discrepancy 49.6%. Conclusions: This study found that preanalytical category are the major source of reported errors in ova system which accounts for 92%. the main reason for sample rejection were due to sample collection process, which is conducted by nurses and phlebotomist

Genetic polymorphisms associated with obesity in the Arab world: a systematic review

Background: Obesity, one of the most common chronic health conditions worldwide, is a multifactorial disease caused by complex genetic and environmental interactions. Several association studies have revealed a considerable number of candidate loci for obesity; however, the genotype–phenotype correlations remain unclear. To date, no comprehensive systematic review has been conducted to investigate the genetic risk factors for obesity among Arabs. Objectives: This study aimed to systematically review the genetic polymorphisms that are significantly associated with obesity in Arabs. Methods: We searched four literature databases (PubMed, Science Direct, Scopus, and Google Scholar) from inception until May 2020 to obtain all reported genetic data related to obesity in Arab populations. Quality assessment and data extraction were performed individually by three investigators. Results: In total, 59 studies comprising a total of 15,488 cases and 9,760 controls were included in the systematic review. A total of 76 variants located within or near 49 genes were reported to be significantly associated with obesity. Among the 76 variants, two were described as unique to Arabs, as they have not been previously reported in other populations, and 19 were reported to be distinctively associated with obesity in Arabs but not in non-Arab populations. Conclusions: There appears to be a unique genetic and clinical susceptibility profile of obesity in Arab patients

Genetic polymorphisms associated with obesity in the Arab world: a systematic review

Background Obesity, one of the most common chronic health conditions worldwide, is a multifactorial disease caused by complex genetic and environmental interactions. Several association studies have revealed a considerable number of candidate loci for obesity; however, the genotype–phenotype correlations remain unclear. To date, no comprehensive systematic review has been conducted to investigate the genetic risk factors for obesity among Arabs. Objectives This study aimed to systematically review the genetic polymorphisms that are significantly associated with obesity in Arabs. Methods We searched four literature databases (PubMed, Science Direct, Scopus, and Google Scholar) from inception until May 2020 to obtain all reported genetic data related to obesity in Arab populations. Quality assessment and data extraction were performed individually by three investigators. Results In total, 59 studies comprising a total of 15,488 cases and 9,760 controls were included in the systematic review. A total of 76 variants located within or near 49 genes were reported to be significantly associated with obesity. Among the 76 variants, two were described as unique to Arabs, as they have not been previously reported in other populations, and 19 were reported to be distinctively associated with obesity in Arabs but not in non-Arab populations. Conclusions There appears to be a unique genetic and clinical susceptibility profile of obesity in Arab patients.Other Information Published in: International Journal of Obesity License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1038/s41366-021-00867-6</p

Attention-deficit hyperactivity disorder : genetic, pharmacogenetic, and metabolomic insights

ADHD is a neurodevelopmental disorder that affects children, adolescents, and adults at a high rate around the globe, resulting in significant impairment. Inattention, impulsivity, restlessness, and hyperactivity are all hallmarks of ADHD. Symptoms may persist into adulthood in 55–66% of all cases. The causes of ADHD remain unclear, but it is believed to be a complex disease with a variety of contributing variables, including heredity, neurodevelopmental problems, severe brain traumas, neuroinflammation, consanguineous marriages, prematurity, and exposure to environmental toxins. Numerous genetic polymorphisms linked with ADHD have been discovered in the twenty-first century. These findings have already given a starting point for the study of ADHD biology and innovative treatment options. Pharmacotherapy using methylphenidate (MPH) seems to be the first-line treatment option for adults with ADHD. Moreover, research has been done on genes that influence the response to MPH among ADHD-affected individuals. Furthermore, a few peripheral biomarkers have been discovered in ADHD adults. In this chapter, the authors summarize current evidence on genetic, pharmacogenetic, and biochemical (metabolomics) investigations in ADHD. Also, the authors address the neurobiology of ADHD, with a focus on functional or structural alterations in the brain of ADHD-affected individuals and their connections with complicated chromosomal variants using imaging genetics methods. In addition, the biological mechanisms involved in ADHD have been summarized. Finally, the scope for additional research for a better understanding of the pathophysiology of ADHD in the context of disrupted signaling pathways is reviewed, which could eventually lead to the discovery of possible therapeutic targets and novel treatment strategies

Principal molecular pathways affected in autism spectrum disorder

Autism spectrum disorder (ASD) development is a highly multifaceted process as evidenced by the complexity of the factors involved in the etiology of ASD, including genetic and nongenetic factors. Several forms of ASD result from genetic alterations in genes that regulate the process of protein synthesis. A growing body of evidence suggests that abnormal synaptic protein synthesis might contribute to ASD and ASD-like clinical features. Several reports of different mutated genes responsible for ASD cases and genetic models have emerged, revealing dysregulation of many crucial signaling pathways. In this chapter, the authors summarize the various factors described to contribute to ASD, both genetic and nongenetic, and their association with WNT, SHH, RA, FGF, and BMP/TGF-β signaling pathways. In addition, the authors discuss the scope for additional research for a better understanding of the pathophysiology of ASD in the context of disrupted signaling pathways, which could help open the doors to identify possible gene targets and novel therapeutic strategies

Association of single nucleotide polymorphisms with dyslipidemia and risk of metabolic disorders in the State of Qatar

Background: Dyslipidemia is recognized as one of the risk factors of cardiovascular diseases (CVDs), type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD). Objective: The study aimed to investigate the association between selected single nucleotide polymorphisms (SNPs) with dyslipidemia and increased susceptibility risks of CVD, NAFLD, and/or T2DM in dyslipidemia patients in comparison with healthy control individuals from the Qatar genome project. Methods: A community-based cross-sectional study was conducted among 2933 adults (859 dyslipidemia patients and 2074 healthy control individuals) from April to December 2021 to investigate the association between 331 selected SNPs with dyslipidemia and increased susceptibility risks of CVD, NAFLD and/or T2DM, and covariates. Results: The genotypic frequencies of six SNPs were found to be significantly different in dyslipidemia patients subjects compared to the control group among males and females. In males, three SNPs were found to be significant, the rs11172113 in over-dominant model, the rs646776 in recessive and over-dominant models, and the rs1111875 in dominant model. On the other hand, two SNPs were found to be significant in females, including rs2954029 in recessive model, and rs1801251 in dominant and recessive models. The rs17514846 SNP was found for dominant and over-dominant models among males and only the dominant model for females. We found that the six SNPs linked to gender type had an influence in relation to disease susceptibility. When controlling for the four covariates (gender, obesity, hypertension, and diabetes), the difference between dyslipidemia and the control group remained significant for the six variants. Finally, males were three times more likely to have dyslipidemia in comparison with females, hypertension was two times more likely to be present in the dyslipidemia group, and diabetes was six times more likely to be in the dyslipidemia group. Conclusion: The current investigation provides evidence of association for a common SNP to coronary heart disease and suggests a sex-dependent effect and encourage potential therapeutic applications. Keywords: Qatar genome project (QGP); cardiovascular disease (CVD); coronary artery disease (CAD); diabetes; dyslipidemia; hypertension; metabolic; non-alcoholic fatty liver disease (NAFLD); single nucleotide polymorphism (SNP). © 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC