The effects of radiofrequency exposure on male fertility: A systematic review of human observational studies with dose-response meta-analysis.

BACKGROUND: The World Health Organization (WHO) is bringing together evidence on radiofrequency electromagnetic field (RF-EMF) exposure in relation to health outcomes, previously identified as priorities for research and evaluation by experts in the field, to inform exposure guidelines. A suite of systematic reviews have been undertaken by a network of topic experts and methodologists to collect, assess and synthesise data relevant to these guidelines. Following the WHO handbook for guideline development and the COSTER conduct guidelines, we systematically reviewed the evidence on the potential effects of RF-EMF exposure on male fertility in human observational studies. METHODS: We conducted a broad and sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; Web of Science and EMF Portal. We also conducted searches of grey literature through relevant databases including OpenGrey, and organisational websites and consulted RF-EMF experts. We hand searched reference lists of included study records and for citations of these studies. We included quantitative human observational studies on the effect of RF-EMF exposure in adult male participants on infertility: sperm concentration; sperm morphology; sperm total motility; sperm progressive motility; total sperm count; and time to pregnancy. Titles and abstracts followed by full texts were screened in blinded duplicate against pre-set eligibility criteria with consensus input from a third reviewer as required. Data extraction from included studies was completed by two reviewers, as was risk of bias assessment using the Office of Health Assessment and Translation (OHAT) tool. We conducted a dose-response meta-analysis as possible and appropriate. Certainty of the evidence was assessed by two reviewers using the OHAT GRADE tool with input from a third reviewer as required. RESULTS: We identified nine studies in this review; seven were general public studies (with the general public as the population of interest) and two were occupational studies (with specific workers/workforces as the population of interest). General public studies. Duration of phone use: The evidence is very uncertain surrounding the effects of RF-EMF on sperm concentration (10/6 mL) (MD (mean difference) per hour of daily phone use 1.6 106/mL, 95 % CI -1.7 to 4.9; 3 studies), sperm morphology (MD 0.15 percentage points of deviation of normal forms per hour, 95 % CI -0.21 to 0.51; 3 studies), sperm progressive motility (MD -0.46 percentage points per hour, 95 % CI -1.04 to 0.13; 2 studies) and total sperm count (MD per hour -0.44 106/ejaculate, 95 % CI -2.59 to 1.7; 2 studies) due to very low-certainty evidence. Four additional studies reported on the effect of mobile phone use on sperm motility but were unsuitable for pooling; only one of these studies identified a statistically significant effect. All four studies were at risk of exposure characterisation and selection bias; two of confounding, selective reporting and attrition bias; three of outcome assessment bias and one used an inappropriate statistical method. Position of phone: There may be no or little effect of carrying a mobile phone in the front pocket on sperm concentration, total count, morphology, progressive motility or on time to pregnancy. Of three studies reporting on the effect of mobile phone location on sperm total motility and, or, total motile count, one showed a statistically significant effect. All three studies were at risk of exposure characterisation and selection bias; two of confounding, selective reporting and attrition bias; three of outcome assessment bias and one used inappropriate statistical method. RF-EMF Source: One study indicates there may be little or no effect of computer or other electric device use on sperm concentration, total motility or total count. This study is at probably high risk of exposure characterisation bias and outcome assessment bias. Occupational studies. With only two studies of occupational exposure to RF-EMF and heterogeneity in the population and exposure source (technicians exposed to microwaves or seamen exposed to radar equipment), it was not plausible to statistically pool findings. One study was at probably or definitely high risk of bias across all domains, the other across domains for exposure characterisation bias, outcome assessment bias and confounding. DISCUSSION: The majority of evidence identified was assessing localised RF-EMF exposure from mobile phone use on male fertility with few studies assessing the impact of phone position. Overall, the evidence identified is very uncertain about the effect of RF-EMF exposure from mobile phones on sperm outcomes. One study assessed the impact of other RF-EMF sources on male fertility amongst the general public and two studies assessed the impact of RF-EMF exposure in occupational cohorts from different sources (radar or microwave) on male fertility. Further prospective studies conducted with greater rigour (in particular, improved accuracy of exposure measurement and appropriate statistical method use) would build the existing evidence base and are required to have greater certainty in any potential effects of RF-EMF on male reproductive outcomes. Prospero Registration: CRD42021265401 (SR3A).

The effects of radiofrequency exposure on adverse female reproductive outcomes: A systematic review of human observational studies with dose-response meta-analysis.

BACKGROUND: To inform radiofrequency electromagnetic field (RF-EMF) exposure guidelines the World Health Organization (WHO) is bringing together evidence on RF-EMF in relation to health outcomes prioritised for evaluation by experts in this field. Given this, a network of topic experts and methodologists have conducted a series of systematic reviews collecting, assessing, and synthesising data of relevance to these guidelines. Here we present a systematic review of the effect of RF-EMF exposure on adverse pregnancy outcomes in human observational studies which follows the WHO handbook for guideline development and the COSTER conduct guidelines. METHODS: We conducted a broad, sensitive search for potentially relevant records within the following bibliographic databases: MEDLINE; Embase; and the EMF Portal. Grey literature searches were also conducted through relevant databases (including OpenGrey), organisational websites and via consultation of RF-EMF experts. We included quantitative human observational studies on the effect of RF-EMF exposure in adults' preconception or pregnant women on pre-term birth, small for gestational age (SGA; associated with intrauterine growth restriction), miscarriage, stillbirth, low birth weight (LBW) and congenital anomalies. In blinded duplicate, titles and abstracts then full texts were screened against eligibility criteria. A third reviewer gave input when consensus was not reached. Citation chaining of included studies was completed. Two reviewers' data extracted and assessed included studies for risk of bias using the Office of Health Assessment and Translation (OHAT) tool. Random effects meta-analyses of the highest versus the lowest exposures and dose-response meta-analysis were conducted as appropriate and plausible. Two reviewers assessed the certainty in each body of evidence using the OHAT GRADE tool. RESULTS: We identified 18 studies in this review; eight were general public studies (with the general public as the population of interest) and 10 were occupational studies (with the population of interest specific workers/workforces). General public studies. From pairwise meta-analyses of general public studies, the evidence is very uncertain about the effects of RF-EMF from mobile phone exposure on preterm birth risk (relative risk (RR) 1.14, 95% confidence interval (CI): 0.97-1.34, 95% prediction interval (PI): 0.83-1.57; 4 studies), LBW (RR 1.14, 95% CI: 0.96-1.36, 95% PI: 0.84-1.57; 4 studies) or SGA (RR 1.13, 95% CI: 1.02-1.24, 95% PI: 0.99-1.28; 2 studies) due to very low-certainty evidence. It was not feasible to meta-analyse studies reporting on the effect of RF-EMF from mobile phone exposure on congenital anomalies or miscarriage risk. The reported effects from the studies assessing these outcomes varied and the studies were at some risk of bias. No studies of the general public assessed the impact of RF-EMF exposure on stillbirth. Occupational studies. In occupational studies, based on dose-response meta-analyses, the evidence is very uncertain about the effects of RF-EMF amongst female physiotherapists using shortwave diathermy on miscarriage due to very low-certainty evidence (OR 1.02 95% CI 0.94-1.1; 2 studies). Amongst offspring of female physiotherapists using shortwave diathermy, the evidence is very uncertain about the effects of RF-EMF on the risk of congenital malformations due to very low-certainty evidence (OR 1.4, 95% CI 0.85 to 2.32; 2 studies). From pairwise meta-analyses, the evidence is very uncertain about the effects of RF-EMF on the risk of miscarriage (RR 1.06, 95% CI 0.96 to 1.18; very low-certainty evidence), pre-term births (RR 1.19, 95% CI 0.32 to 4.37; 3 studies; very low-certainty evidence), and low birth weight (RR 2.90, 95% CI: 0.69 to 12.23; 3 studies; very low-certainty evidence). Results for stillbirth and SGA could not be pooled in meta-analyses. The results from the studies reporting these outcomes were inconsistent and the studies were at some risk of bias. DISCUSSION: Most of the evidence identified in this review was from general public studies assessing localised RF-EMF exposure from mobile phone use on female reproductive outcomes. In occupational settings, each study was of heterogenous whole-body RF-EMF exposure from radar, short or microwave diathermy, surveillance and welding equipment and its effect on female reproductive outcomes. Overall, the body of evidence is very uncertain about the effect of RF-EMF exposure on female reproductive outcomes. Further prospective studies conducted with greater rigour (particularly improved accuracy of exposure measurement and using appropriate statistical methods) are required to identify any potential effects of RF-EMF exposure on female reproductive outcomes of interest.

Predictors of Post-Operative Hospital Length of Stay Following Complete Repair of Tetralogy of Fallot in a Pediatric Cohort in the North of England.

We sought to estimate the median post-operative length of stay (PLOS) and predictors of PLOS following tetralogy of Fallot (ToF) repair at a specialist surgical center in the North of England. The local National Congenital Heart Disease Audit dataset was used to identify patients aged < 2 years who underwent surgical repair for ToF between 1 January 1986 and 13 May 2022. Coefficients representing the median change in PLOS (days) according to predictors were estimated using Quantile regression. There were 224 patients (59.4% male, median age = 9 months, interquartile range (IQR) 5-13 months) with a median PLOS of 9 days (IQR 7-13). In the univariable regression, age (months) and weight (kg) at operation (ß = - 0.17, 95% CI: - 0.33, - 0.01) and (ß = - 0.53, 95% CI: - 0.97, - 0.10), previous (cardiac or thoracic) procedure (ß = 5, 95% CI:2.38, 7.62), procedure urgency (elective vs urgent) (ß = 2.8, 95% CI:0.39, 5.21), bypass time (mins) (ß = 0.03, 95% CI:0.01, 0.05), cross-clamp time (mins) (ß = 0.03, 95% CI:0.01, 0.06) and duration of post-operative intubation (days) (ß = 0.81, 95% CI:0.67, 0.96), were significantly associated with PLOS. Previous procedure and intubation time remained significant in multivariable analyses. Some patient and operative factors can predict PLOS following complete ToF repair. Information on PLOS is important for health professionals to support parents in preparing for their child's discharge and to make any necessary practical arrangements. Health commissioners can draw on evidence-based guidance for resource planning. The small sample size may have reduced the power to detect small effect sizes, but this regional study serves as a foundation for a larger national study.

A systematic review and meta-analysis of school and cognitive function domains of health-related quality of life measures for children and young adults with congenital heart disease.

BACKGROUND: Research on cognitive and school functioning domains of health-related quality of life (HRQOL) for children and adolescents with congenital heart disease (CHD) presents inconsistencies. OBJECTIVES: To summarize and synthesize data on school and cognitive function domains of HRQOL for children and young people (CYP) with CHD. METHODS: Five electronic databases MEDLINE, Scopus, PsycINFO, EMBASE, ERI, and citations were systematically searched. We included original-research articles reporting the cognitive and school function domains of HRQOL for children and young people with CHD (child and parent reports included). Both fixed and random-effects meta-analyses were performed to estimate pooled mean test scores for cognitive and school function. A total of 34 studies met our inclusion criteria and were synthesized narratively, 17 studies were included in formal meta-analyses. RESULTS: Self-reported cognitive function was lower for children and young people with CHD than healthy controls (SMD -0.28 (-0.42, -0.15)). Parental reports demonstrated similar results to self-reports (SMD -0.54 (-0.91, -0.18)). School function was lower in children and young people with CHD compared with healthy controls in self-reported (SMD -0.30 (-0.48, -0.13)) and parent reported HRQOL (SMD -0.49 (0.64, -0.36)). Self-reported school function domain scores were lower for young (<8 years) (SMD -0.65 (-1.32, 0.03)) and older children (8-18 years) (SMD -0.25 (-0.47, -0.03)) with CHD than their peers. Similarly, parents reported lower school function domain scores for young (<8 years) (SMD -0.68 (-1.29, -0.07)) and older (8-18 years) (SMD -0.46 (-068, -0.25)) children with CHD than typically developing peers. CONCLUSION: Children born with CHD may experience lower cognitive and school function HRQOL scores than healthy controls (self and proxy-report). This is consistent with a subgroup meta-analysis of young (<8 years) and older (8 years old or more) children with CHD reporting lower school function scores compared to controls.

Impact of the COVID-19 pandemic on expectant and new parents' experience of pregnancy, childbirth, breast feeding, parental responsiveness and sensitivity, and bonding and attunement in high-income countries: a systematic review of the evidence.

OBJECTIVES: To review the evidence on how pregnancy, birth experience, breast feeding, parental responsiveness and sensitivity, and bonding and attunement were impacted by COVID-19. METHODS: We searched eight literature databases and websites of relevant UK-based organisations. The review focused on evidence during pregnancy and the early years (0-5 years). Studies of any study design published in English from 1 March 2020 to 15 March 2021 and conducted in high-income countries were included. Screening and data extraction were undertaken in duplicate. Evidence was synthesised using a narrative approach. Study quality of included studies was assessed using the Mixed Methods Appraisal Tool. RESULTS: The search yielded 9776 publications, of which 26 met our inclusion criteria. Significant knowledge gaps on how COVID-19 affected pregnancy and breast feeding limited healthcare providers' ability to provide consistent evidence-based information and care at the start of the pandemic. There was an enduring sense of loss about loved ones being restricted from taking part in key moments. Parents were concerned about the limitations of virtual healthcare provision. Some parents reported more opportunities for responsive breast feeding and improved parent-infant bonding due to reduced social and work pressures. Women from minoritised ethnic groups were less likely to continue breast feeding and attributed this to a lack of face-to-face support. CONCLUSIONS: The evidence suggests that new and expectant families have been both negatively and positively impacted by the COVID-19 pandemic and the resulting restrictions. The impacts on parents' opportunities to bond with their young children and to be attuned to their needs were felt unequally. It is important that emergency response policies consider the mother and the partner as a family unit when making changes to the delivery of maternal and child health and care services, so as to mitigate the impact on the family and existing health inequalities. PROSPERO REGISTRATION NUMBER: CRD42021236769.

The effects of radiofrequency exposure on male fertility and adverse reproductive outcomes: A protocol for two systematic reviews of human observational studies with meta-analysis.

BACKGROUND: The World Health Organization (WHO) is bringing together evidence on radiofrequency electromagnetic field (RF-EMF) exposure in relation to health outcomes, previously identified as priorities for evaluation by experts in the field, to inform exposure guidelines. A suite of systematic reviews are being undertaken by a network of topic experts and methodologists in order to collect, assess and synthesise data relevant to these guidelines. Here, we present the protocol for the systematic review on the effect of exposure to RF on adverse reproductive outcomes (human observational studies), also referred to as Systematic Review (SR) 3 within the series of systematic reviews currently being commissioned. OBJECTIVES: Following the WHO handbook for guideline development and the COSTER conduct guidelines, we will systematically review the effect of RF-EMF exposure on both male fertility (SR3A) and adverse pregnancy outcomes (SR3B) in human observational studies. Herein we adhere to the PRISMA-P reporting guidelines. DATA SOURCES: We will conduct a broad search for potentially relevant records relevant for both reviews within the following bibliographic databases: MEDLINE; Embase; and EMF Portal. We will also conduct searches of grey literature through relevant databases and organisational websites. RF-EMF experts will also be consulted. We will hand search citation and reference lists of included study records. STUDY ELIGIBILITY CRITERIA: We will include quantitative human observational studies on the effect of RF-EMF exposure: (in SR3A) in adult male participants on infertility, sperm morphology, concentration or total sperm count or motility; and (in SR3B) in preconception adults or pregnant women on preterm birth, small for gestational age (associated with intrauterine growth restriction), miscarriage, stillbirth and congenital anomalies. STUDY APPRAISAL AND SYNTHESIS METHODS: Titles, abstracts and then full texts will be screened in blinded duplicate against eligibility criteria with input from a third reviewer as required. Data extraction from included studies will be completed by two reviewers as will risk of bias assessment using the Office of Health Assessment and Translation (OHAT) tool. If appropriate we will undertake meta-analysis to pool effect measures and explore heterogeneity using sub-group analyses or meta-regression as feasible. We will conduct sensitivity analysis to assess the impact of any assumptions made throughout the review process. The OHAT methodology, based on the GRADE guidelines for evidence assessment, will be used to evaluate the certainty of evidence per outcome and to conclude the level of evidence of a health effect. CONCLUSION: This manuscript details the protocols for two systematic reviews. The aims of publishing details of both protocols are to: pre-specify their scope and methods; reduce the impact of reviewer bias; promote transparency and replicability; and improve the review process. PROSPERO REGISTRATION: CRD42021265401 (SR3A), CRD42021266268 (SR3B).

The Tyrosine Kinase-Driven Networks of Novel Long Non-coding RNAs and Their Molecular Targets in Myeloproliferative Neoplasms.

Recent research has focused on the mechanisms by which long non-coding RNAs (lncRNAs) modulate diverse cellular processes such as tumorigenesis. However, the functional characteristics of these non-coding elements in the genome are poorly understood at present. In this study, we have explored several mechanisms that involve the novel lncRNA and microRNA (miRNA) axis participating in modulation of drug response and the tumor microenvironment of myeloproliferative neoplasms (MPNs). We identified novel lncRNAs via mRNA sequencing that was applied to leukemic cell lines derived from BCR-ABL1-positive and JAK2-mutant MPNs under treatment with therapeutic tyrosine kinase inhibitors (TKI). The expression and sequence of novel LNC000093 were further validated in both leukemic cells and normal primary and pluripotent cells isolated from human blood, including samples from patients with chronic myelogenous leukemia (CML). Downregulation of LNC000093 was validated in TKI-resistant CML while a converse expression pattern was observed in blood cells isolated from TKI-sensitive CML cases. In addition to BCR-ABL1-positive CML cells, the driver mutation JAK2-V617F-regulated lncRNA BANCR axis was further identified in BCR-ABL1-negative MPNs. Further genome-wide validation using MPN patient specimens identified 23 unique copy number variants including the 7 differentially expressed lncRNAs from our database. The newly identified LNC000093 served as a competitive endogenous RNA for miR-675-5p and reversed the imatinib resistance in CML cells through regulating RUNX1 expression. The extrinsic function of LNC000093 in exosomal H19/miR-675-induced modulation for the microenvironment was also determined with significant effect on VEGF expression.