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European Journal of Medical Research Aug 2023The reactivation of herpesviruses (HHV) in COVID-19 patients is evident in the literature. Several reports have been published regarding the reactivation of these... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The reactivation of herpesviruses (HHV) in COVID-19 patients is evident in the literature. Several reports have been published regarding the reactivation of these viruses (HSV, VZV, EBV, and CMV) among those who got COVID-19 vaccines. In this study, we aimed to review the current evidence to assess whether HHVs reactivation has any association with the prior administration of COVID-19 vaccines.
METHODS
A systematic search was conducted on 25 September 2022 in PubMed/MEDLINE, Web of Science, and EMBASE. We included all observational studies, case reports, and case series which reported the reactivation of human herpesviruses following administration of COVID-19 vaccines.
RESULTS
Our systematic search showed 80 articles that meet the eligibility criteria. Among the evaluated COVID-19 vaccines, most of the vaccines were mRNA based. Evidence from observational studies showed the possible relation between COVID-19 vaccine administration and VZV and HSV reactivation. The results of our proportion meta-analysis showed that the rate of VZV reactivation among those who received the COVID-19 vaccine was 14 persons per 1000 vaccinations (95% CI 2.97-32.80). Moreover, our meta-analysis for HSV reactivation showed the rate of 16 persons per 1000 vaccinations (95% CI 1.06-46.4). Furthermore, the evidence from case reports/series showed 149 cases of HHV reactivation. There were several vaccines that caused reactivation including BNT162b2 mRNA or Pfizer-BioNTech (n = 76), Oxford-AstraZeneca (n = 22), mRNA-1273 or Moderna (n = 17), Sinovac (n = 4), BBIBP-CorV or Sinopharm (n = 3), Covaxin (n = 3), Covishield (n = 3), and Johnson and Johnson (n = 1). Reactivated HHVs included varicella-zoster virus (VZV) (n = 114), cytomegalovirus (CMV) (n = 15), herpes simplex virus (HSV) (n = 14), Epstein-Barr virus (EBV) (n = 6), and HHV-6 (n = 2). Most cases reported their disease after the first dose of the vaccine. Many patients reported having comorbidities, of which hypertension, diabetes mellitus, dyslipidemia, chicken pox, and atrial fibrillation were common.
CONCLUSION
In conclusion, our study showed the possible association between COVID-19 vaccination and herpesvirus reactivation. The evidence for VZV and HSV was supported by observational studies. However, regarding other herpesviruses (EBV and CMV), further research especially from observational studies and clinical trials is required to elucidate the interaction between COVID-19 vaccination and their reactivation.
Topics: Humans; BNT162 Vaccine; ChAdOx1 nCoV-19; COVID-19; COVID-19 Vaccines; Cytomegalovirus; Cytomegalovirus Infections; Epstein-Barr Virus Infections; Herpesviridae Infections; Herpesvirus 3, Human; Herpesvirus 4, Human; Simplexvirus; Vaccination; Viruses
PubMed: 37559096
DOI: 10.1186/s40001-023-01238-9 -
The Cochrane Database of Systematic... Oct 2023Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of... (Review)
Review
BACKGROUND
Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of the varicella episode, the virus can remain latent in the sensitive dorsal ganglia of the spine. Years later, with declining immunity, the varicella zoster virus (VZV) can reactivate and cause herpes zoster, an extremely painful condition that can last many weeks or months and significantly compromise the quality of life of the affected person. The natural process of ageing is associated with a reduction in cellular immunity, and this predisposes older adults to herpes zoster. Vaccination with an attenuated form of the VZV activates specific T-cell production avoiding viral reactivation. Two types of herpes zoster vaccines are currently available. One of them is the single-dose live attenuated zoster vaccine (LZV), which contains the same live attenuated virus used in the chickenpox vaccine, but it has over 14-fold more plaque-forming units of the attenuated virus per dose. The other is the recombinant zoster vaccine (RZV) which does not contain the live attenuated virus, but rather a small fraction of the virus that cannot replicate but can boost immunogenicity. The recommended schedule for the RZV is two doses two months apart. This is an update of a Cochrane Review first published in 2010, and updated in 2012, 2016, and 2019.
OBJECTIVES
To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults.
SEARCH METHODS
For this 2022 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2022, Issue 10), MEDLINE (1948 to October 2022), Embase (2010 to October 2022), CINAHL (1981 to October 2022), LILACS (1982 to October 2022), and three trial registries.
SELECTION CRITERIA
We included studies involving healthy older adults (mean age 60 years or older). We included randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine (any dose and potency) versus any other type of intervention (e.g. varicella vaccine, antiviral medication), placebo, or no intervention (no vaccine). Outcomes were cumulative incidence of herpes zoster, adverse events (death, serious adverse events, systemic reactions, or local reaction occurring at any time after vaccination), and dropouts.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included two new studies involving 1736 participants in this update. The review now includes a total of 26 studies involving 90,259 healthy older adults with a mean age of 63.7 years. Only three studies assessed the cumulative incidence of herpes zoster in groups that received vaccines versus placebo. Most studies were conducted in high-income countries in Europe and North America and included healthy Caucasians (understood to be white participants) aged 60 years or over with no immunosuppressive comorbidities. Two studies were conducted in Japan and one study was conducted in the Republic of Korea. Sixteen studies used LZV. Ten studies tested an RZV. The overall certainty of the evidence was moderate, which indicates that the intervention probably works. Most data for the primary outcome (cumulative incidence of herpes zoster) and secondary outcomes (adverse events and dropouts) came from studies that had a low risk of bias and included a large number of participants. The cumulative incidence of herpes zoster at up to three years of follow-up was lower in participants who received the LZV (one dose subcutaneously) than in those who received placebo (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.43 to 0.56; risk difference (RD) 2%; number needed to treat for an additional beneficial outcome (NNTB) 50; moderate-certainty evidence) in the largest study, which included 38,546 participants. There were no differences between the vaccinated and placebo groups for serious adverse events (RR 1.08, 95% CI 0.95 to 1.21) or deaths (RR 1.01, 95% CI 0.92 to 1.11; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of one or more adverse events (RR 1.71, 95% CI 1.38 to 2.11; RD 23%; number needed to treat for an additional harmful outcome (NNTH) 4.3) and injection site adverse events (RR 3.73, 95% CI 1.93 to 7.21; RD 28%; NNTH 3.6; moderate-certainty evidence) of mild to moderate intensity. These data came from four studies with 6980 participants aged 60 years or older. Two studies (29,311 participants for safety evaluation and 22,022 participants for efficacy evaluation) compared RZV (two doses intramuscularly, two months apart) versus placebo. Participants who received the new vaccine had a lower cumulative incidence of herpes zoster at 3.2 years follow-up (RR 0.08, 95% CI 0.03 to 0.23; RD 3%; NNTB 33; moderate-certainty evidence), probably indicating a favourable profile of the intervention. There were no differences between the vaccinated and placebo groups in cumulative incidence of serious adverse events (RR 0.97, 95% CI 0.91 to 1.03) or deaths (RR 0.94, 95% CI 0.84 to 1.04; moderate-certainty evidence). The vaccinated group had a higher cumulative incidence of adverse events, any systemic symptom (RR 2.23, 95% CI 2.12 to 2.34; RD 33%; NNTH 3.0), and any local symptom (RR 6.89, 95% CI 6.37 to 7.45; RD 67%; NNTH 1.5). Although most participants reported that their symptoms were of mild to moderate intensity, the risk of dropouts (participants not returning for the second dose, two months after the first dose) was higher in the vaccine group than in the placebo group (RR 1.25, 95% CI 1.13 to 1.39; RD 1%; NNTH 100, moderate-certainty evidence). Only one study reported funding from a non-commercial source (a university research foundation). All other included studies received funding from pharmaceutical companies. We did not conduct subgroup and sensitivity analyses AUTHORS' CONCLUSIONS: LZV (single dose) and RZV (two doses) are probably effective in preventing shingles disease for at least three years. To date, there are no data to recommend revaccination after receiving the basic schedule for each type of vaccine. Both vaccines produce systemic and injection site adverse events of mild to moderate intensity. The conclusions did not change in relation to the previous version of the systematic review.
Topics: Humans; Aged; Middle Aged; Herpesvirus 3, Human; Herpes Zoster Vaccine; Chickenpox; Herpes Zoster; Vaccines, Attenuated
PubMed: 37781954
DOI: 10.1002/14651858.CD008858.pub5 -
Frontiers in Immunology 2022To investigate the efficacy, effectiveness and safety of recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL) in immunocompetent and immunocompromised subjects. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the efficacy, effectiveness and safety of recombinant zoster vaccine (RZV) and zoster vaccine live (ZVL) in immunocompetent and immunocompromised subjects.
METHODS
Data sources: PubMed, EMBASE, Cochrane Library, and Web of Science databases (up to Jan 2022) were searched to identify English articles. Search terms included randomized controlled trials (RCTs), observational studies, herpes zoster, RZV, ZVL. Study Selection: Only randomized controlled trials (RCTs) evaluating vaccine efficacy and safety and observational studies assessing vaccine effectiveness (after a vaccine was approved for marketing) were included. Data Extraction: Two researchers independently screened the literature, extracted the data, and checked the each other results.
RESULTS
Seventeen RCTs and 19 cohort studies were included. Among immunocompetent subjects, RZV was superior to ZVL at wide intervals (relative vaccine efficacy: 84%, 95% CI: 53%-95%; relative vaccine effectiveness: 49%, 95% CI: 21%-67%), across genders and subjects aged ≥ 60 years. Among immunocompromised subjects, RZV was superior to placebo in terms of vaccine efficacy (60%, 95% CI: 49%-69%). There was no difference between ZVL and placebo in those with selected immunosuppressive conditions. RZV was 45% (95% CI: 30%-59%) superior to ZVL in real-world practice. Compared with placebo, adverse events related to RZV were primarily related to injection-site and systemic, and RZV did not increase the risk of serious adverse events (SAEs) or death. There was no difference in the incidence of adverse events between groups with and without immunosuppression.
CONCLUSIONS
Both RZV and ZVL can reduce the risk of herpes zoster in both immunocompetent and immunocompromised subjects. RZV was well-tolerated in the study population and demonstrated stronger protection than ZVL.
SYSTEMATIC REVIEW REGISTRATION
Prospero CRD42022310495.
Topics: Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Network Meta-Analysis; Vaccines, Synthetic
PubMed: 36248796
DOI: 10.3389/fimmu.2022.978203 -
The Lancet. Healthy Longevity Apr 2022Given the substantial impact of herpes zoster on health and quality of life, and its considerable economic burden, prevention through vaccination is a priority. We aimed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Given the substantial impact of herpes zoster on health and quality of life, and its considerable economic burden, prevention through vaccination is a priority. We aimed to evaluate the effectiveness of the herpes zoster vaccines (recombinant zoster vaccine [RZV] and zoster vaccine live [ZVL]) against incident herpes zoster and postherpetic neuralgia in older adults.
METHODS
We did a systematic review and meta-analysis of studies assessing the effectiveness of herpes zoster vaccines in adults aged 50 years or older, compared with no vaccination or another vaccine. We searched published literature on MEDLINE, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ProQuest Central, and Dimensions, as well as unpublished studies, grey literature, and the reference lists of included studies. Observational studies published in any language between May 25, 2006, and Dec 31, 2020, were included. Eligible studies were appraised for methodological quality using standardised critical appraisal instruments from the Joanna Briggs Institute, and data were extracted from selected studies using a standardised tool. Random-effects meta-analysis models were used to estimate pooled vaccine effectiveness for outcomes of interest (herpes zoster, herpes zoster ophthalmicus, and postherpetic neuralgia) among clinically and methodologically comparable studies, with a fixed-effects model also used for herpes zoster ophthalmicus. Vaccine effectiveness was also assessed in people with comorbidities. As a post-hoc analysis, a forward citation search was done on Jan 31, 2021. This study is registered on PROSPERO, CRD42021232383.
FINDINGS
Our search identified 1240 studies, of which 1162 were excluded based on title and abstract screening. A further 56 articles were excluded on reading the full text. 22 studies (21 cohort studies and one case-control study, involving 9 536 086 participants and 3·35 million person-years in the USA, UK, Canada, and Sweden) were included in the quantitative analysis. Of these, 13 articles were included in the meta-analysis. The overall quality of evidence was very low for all outcomes. The pooled vaccine effectiveness for ZVL against herpes zoster in adults was 45·9% (95% CI 42·2-49·4; seven studies). The vaccine effectiveness for ZVL against postherpetic neuralgia was 59·7% (58·4-89·7; three studies) and against herpes zoster ophthalmicus (in a fixed-effects model) was 30·0% (20·5-38·4; two studies). ZVL was effective in preventing herpes zoster in people with comorbidities, including diabetes (vaccine effectiveness 49·8%, 45·1-54·1; three studies), chronic kidney disease (54·3%, 49·0-59·1; four studies), liver disease (52·9%, 41·6-62·1; two studies), heart disease (52·3%, 45·0-58·7; two studies), and lung disease (49·0%, 32·2-66·2; two studies). In a post-hoc analysis of two studies from the USA published after 2020, the pooled vaccine effectiveness for RZV against herpes zoster in adults was 79·2% (57·6-89·7). Substantial heterogeneity (I≥75%) was observed in 50% of the meta-analyses.
INTERPRETATION
ZVL and RZV are effective in preventing herpes zoster in routine clinical practice. ZVL also reduces the risk of postherpetic neuralgia. Selection bias and confounding by unmeasured variables are inherent challenges of observational studies based on large health-care databases. Nevertheless, these findings will reassure policy makers, health practitioners, and the public that the vaccinations currently available for herpes zoster vaccination programmes are effective at preventing herpes zoster and related complications.
FUNDING
None.
Topics: Aged; Case-Control Studies; Herpes Zoster Ophthalmicus; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Neuralgia, Postherpetic; Quality of Life; Vaccine Efficacy; Vaccines, Synthetic
PubMed: 36098300
DOI: 10.1016/S2666-7568(22)00039-3 -
Bulletin of the World Health... May 2020To generate global and regional estimates for the prevalence and incidence of herpes simplex virus (HSV) type 1 and type 2 infection for 2016. (Comparative Study)
Comparative Study
OBJECTIVE
To generate global and regional estimates for the prevalence and incidence of herpes simplex virus (HSV) type 1 and type 2 infection for 2016.
METHODS
To obtain data, we undertook a systematic review to identify studies up to August 2018. Adjustments were made to account for HSV test sensitivity and specificity. For each World Health Organization (WHO) region, we applied a constant incidence model to pooled prevalence by age and sex to estimate the prevalence and incidence of HSV types 1 and 2 infections. For HSV type 1, we apportioned infection by anatomical site using pooled estimates of the proportions that were oral and genital.
FINDINGS
In 2016, an estimated 491.5 million people (95% uncertainty interval, UI: 430.4 million-610.6 million) were living with HSV type 2 infection, equivalent to 13.2% of the world's population aged 15-49 years. An estimated 3752.0 million people (95% UI: 3555.5 million-3854.6 million) had HSV type 1 infection at any site, equivalent to a global prevalence of 66.6% in 0-49-year-olds. Differing patterns were observed by age, sex and geographical region, with HSV type 2 prevalence being highest among women and in the WHO African Region.
CONCLUSION
An estimated half a billion people had genital infection with HSV type 2 or type 1, and several billion had oral HSV type 1 infection. Millions of people may also be at higher risk of acquiring human immunodeficiency virus (HIV), particularly women in the WHO African Region who have the highest HSV type 2 prevalence and exposure to HIV.
Topics: Adolescent; Adult; Age Distribution; Child; Child, Preschool; Female; Global Health; Herpes Genitalis; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Incidence; Infant; Male; Middle Aged; Prevalence; Young Adult
PubMed: 32514197
DOI: 10.2471/BLT.19.237149 -
Clinical Infectious Diseases : An... Oct 2020The primary reported risk factors for herpes zoster (HZ) include increasing age and immunodeficiency, yet estimates of HZ risk by immunocompromising condition have not...
BACKGROUND
The primary reported risk factors for herpes zoster (HZ) include increasing age and immunodeficiency, yet estimates of HZ risk by immunocompromising condition have not been well characterized. We undertook a systematic literature review to estimate the HZ risk in immunocompromised patients.
METHODS
We systematically reviewed studies that examined the risk of HZ and associated complications in adult patients with hematopoietic cell transplants (HCT), cancer, human immunodeficiency virus (HIV), and solid organ transplant (SOT). We identified studies in PubMed, Embase, Medline, Cochrane, Scopus, and clinicaltrials.gov that presented original data from the United States and were published after 1992. We assessed the risk of bias with Cochrane or Grading of Recommendations Assessment, Development, and Evaluation methods.
RESULTS
We identified and screened 3765 records and synthesized 34 studies with low or moderate risks of bias. Most studies that were included (32/34) reported at least 1 estimate of the HZ cumulative incidence (range, 0-41%). There were 12 studies that reported HZ incidences that varied widely within and between immunocompromised populations. Incidence estimates ranged from 9 to 92 HZ cases/1000 patient-years and were highest in HCT, followed by hematologic malignancies, SOT, and solid tumor malignancies, and were lowest in people living with HIV. Among 17 HCT studies, the absence of or use of antiviral prophylaxis at <1 year post-transplant was associated with a higher HZ incidence.
CONCLUSIONS
HZ was common among all immunocompromised populations studied, exceeding the expected HZ incidence among immunocompetent adults aged ≥60 years. Better evidence of the incidence of HZ complications and their severity in immunocompromised populations is needed to inform economic and HZ vaccine policies.
Topics: Adult; Herpes Zoster; Herpes Zoster Vaccine; Herpesvirus 3, Human; Humans; Immunocompromised Host; Incidence; Middle Aged; Neuralgia, Postherpetic; United States
PubMed: 31677266
DOI: 10.1093/cid/ciz1090 -
Microbial Pathogenesis Apr 2023The aim of this study was to investigate the prevalence and potential association between infection with different herpes viruses and multiple sclerosis (MS). (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this study was to investigate the prevalence and potential association between infection with different herpes viruses and multiple sclerosis (MS).
METHODS
A systematic literature search was performed by finding relevant cross-sectional and case-control studies from a large online database. Heterogeneity, Odds ratio (OR), and corresponding 95% Confidence interval (CI) were applied to all studies by meta-analysis and forest plots. The analysis was performed using Stata Software v.14.
RESULTS
One hundred and thirty-four articles (289 datasets) were included in the meta-analysis, 128 (245 datasets) of which were case/control and the rest were cross-sectional. The pooled prevalence of all human herpes viruses among MS patients was 50% (95% CI: 45-55%; I2 = 96.91%). In subgroup analysis, the pooled prevalence of Herpes simplex virus (HSV), Varicella-zoster virus (VZV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Human herpes virus 6 (HHV-6), Human herpes virus 7 (HHV-7), and Human herpes virus 8 (HHV-8) was 32%, 52%, 74%, 41%, 39% 28%, and 28%, respectively. An association was found between infection with human herpes viruses and MS [summary OR 2.07 (95% CI (1.80-2.37); I2 = 80%)].
CONCLUSION
The results of the present study showed that EBV, VZV, and HHV-6 infection are associated with multiple sclerosis and can be considered as potential risk factors for MS. Although the exact molecular mechanism of the role of herpes viruses in the development of MS is still unknown, it seems that molecular mimicry, the release of autoreactive antibodies, and inflammation in the CNS following viral infection can be important factors in the induction of MS.
Topics: Humans; Multiple Sclerosis; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Simplexvirus; Herpesviridae Infections; Herpesvirus 3, Human; Viruses
PubMed: 36775211
DOI: 10.1016/j.micpath.2023.106031 -
Autonomic Neuroscience : Basic &... Nov 2022Autonomic dysfunction has been occasionally described in varicella-zoster virus (VZV) infection, while few systematic reviews are available. We systematically review... (Review)
Review
BACKGROUND AND PURPOSE
Autonomic dysfunction has been occasionally described in varicella-zoster virus (VZV) infection, while few systematic reviews are available. We systematically review autonomic dysfunction due to VZV infection.
METHODS
This study followed the PRISMA guideline, and three databases were researched and included cross-sectional studies in full-length publications in the English language using appropriate search keywords.
RESULTS
A total of 102 articles were identified initially; finally 45 studies were used for review, comprising pupillomotor dysfunction in 4, sudomotor dysfunction in 2, cardiovascular dysfunction in 2, gastrointestinal dysfunction in 14, and urogenital dysfunction in 23. They can be summarized as (1) VZV infection rarely produces orthostatic hypotension, which involves diffuse sympathetic dysfunction by polyneuropathy. (2) In contrast, VZV infection produces dysfunction of the bladder and the bowel, which involves segmental parasympathetic or sympathetic dysfunction by dorsal root ganglionopathy.
CONCLUSIONS
Awareness of VZV-related autonomic dysfunction is important, because such patients may first visit a gastroenterology or urology clinic. Close collaboration among neurologists, dermatologists, gastroenterologists, and urologists is important to start early antiviral agents and maximize bowel and bladder care in such patients.
Topics: Autonomic Nervous System Diseases; Chickenpox; Cross-Sectional Studies; Herpes Zoster; Herpesvirus 3, Human; Humans
PubMed: 35863181
DOI: 10.1016/j.autneu.2022.103018 -
Virology Journal Dec 2023Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cervical cancer (CC) is one of the most common gynecologic tumors among women around the world. Although the etiological role of human papillomavirus (HPV) in CC is well established, other factors in CC carcinogenesis remains unclear. Here, we performed a systematic review and meta-analysis to explore the association between infections of human herpesvirus (HHVs) and CC risk.
METHODS
Embase and PubMed databases were utilized to search the relevant studies. The revised JBI Critical Appraisal Tool was used to assess the quality of the included studies. Prevalence and odds ratios (ORs) with 95% confidence intervals (CI) were calculated to evaluate the association between viral infection and CC or precancerous cervical lesions (PCL).
RESULTS
Totally 67 eligible studies involving 7 different HHVs were included in meta-analysis. We found an increased risk of CC or PCL that was associated with the overall infection of HHVs (CC, OR = 2.74, 95% CI 2.13-3.53; PCL, OR = 1.95, 95% CI 1.58-2.41). Subgroup analysis showed a trend towards positive correlations between herpes simplex virus type 2 (HSV-2) infection and CC (OR = 3.01, 95% CI 2.24 to 4.04) or PCL (OR = 2.14, 95% CI 1.55 to 2.96), and the same is true between Epstein-Barr virus (EBV) infection and CC (OR = 4.89, 95% CI 2.18 to 10.96) or PCL (OR = 3.55, 95% CI 2.52 to 5.00). However, for HSV-1 and cytomegalovirus (HCMV), there was no association between viral infection and CC or PCL. By contrast, the roles of HHV-6, HHV-7, and Kaposi sarcoma-associated herpesvirus (KSHV) in cervical lesions were unclear due to the limited number of studies.
CONCLUSIONS
This study provided evidence that HHVs infection as a whole increase the risk of CC incidence. In addition, some types of HHVs such as EBV and HSV-2 may serve as potential targets in the development of new interventions or therapeutic strategies for cervical lesions.
Topics: Humans; Female; Epstein-Barr Virus Infections; Uterine Cervical Neoplasms; Herpesvirus 4, Human; Herpesviridae Infections; Herpesviridae; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human
PubMed: 38049836
DOI: 10.1186/s12985-023-02234-5 -
The Lancet. Psychiatry May 2020Prenatal and perinatal insults are implicated in the aetiopathogenesis of psychotic disorders but the consistency and magnitude of their associations with psychosis have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prenatal and perinatal insults are implicated in the aetiopathogenesis of psychotic disorders but the consistency and magnitude of their associations with psychosis have not been updated for nearly two decades. The aim of this systematic review and meta-analysis was to provide a comprehensive and up-to-date synthesis of the evidence on the association between prenatal or perinatal risk and protective factors and psychotic disorders.
METHODS
In this systematic review and meta-analysis, we searched the Web of Science database for articles published up to July 20, 2019. We identified cohort and case-control studies examining the association (odds ratio [OR]) between prenatal and perinatal factors and any International Classification of Diseases (ICD) or Diagnostic and Statistical Manual of Mental Disorders (DSM) non-organic psychotic disorder with a healthy comparison group. Other inclusion criteria were enough data available to do the analyses, and non-overlapping datasets. We excluded reviews, meta-analyses, abstracts or conference proceedings, and articles with overlapping datasets. Data were extracted according to EQUATOR and PRISMA guidelines. Extracted variables included first author, publication year, study type, sample size, type of psychotic diagnosis (non-affective psychoses or schizophrenia-spectrum disorders, affective psychoses) and diagnostic instrument (DSM or ICD and version), the risk or protective factor, and measure of association (primary outcome). We did random-effects pairwise meta-analyses, Q statistics, I index, sensitivity analyses, meta-regressions, and assessed study quality and publication bias. The study protocol was registered at PROSPERO, CRD42017079261.
FINDINGS
152 studies relating to 98 risk or protective factors were eligible for analysis. Significant risk factors were: maternal age younger than 20 years (OR 1·17) and 30-34 years (OR 1·05); paternal age younger than 20 years (OR 1·31) and older than 35 years (OR 1·28); any maternal (OR 4·60) or paternal (OR 2·73) psychopathology; maternal psychosis (OR 7·61) and affective disorder (OR 2·26); three or more pregnancies (OR 1·30); herpes simplex 2 (OR 1·35); maternal infections not otherwise specified (NOS; OR 1·27); suboptimal number of antenatal visits (OR 1·83); winter (OR 1·05) and winter to spring (OR 1·05) season of birth in the northern hemisphere; maternal stress NOS (OR 2·40); famine (OR 1·61); any famine or nutritional deficits in pregnancy (OR 1·40); maternal hypertension (OR 1·40); hypoxia (OR 1·63); ruptured (OR 1·86) and premature rupture (OR 2·29) of membranes; polyhydramnios (OR 3·05); definite obstetric complications NOS (OR 1·83); birthweights of less than 2000 g (OR 1·84), less than 2500 g (OR 1·53), or 2500-2999 g (OR 1·23); birth length less than 49 cm (OR 1·17); small for gestational age (OR 1·40); premature birth (OR 1·35), and congenital malformations (OR 2·35). Significant protective factors were maternal ages 20-24 years (OR 0·93) and 25-29 years (OR 0·92), nulliparity (OR 0·91), and birthweights 3500-3999 g (OR 0·90) or more than 4000 g (OR 0·86). The results were corrected for publication biases; sensitivity and meta-regression analyses confirmed the robustness of these findings for most factors.
INTERPRETATION
Several prenatal and perinatal factors are associated with the later onset of psychosis. The updated knowledge emerging from this study could refine understanding of psychosis pathogenesis, enhance multivariable risk prediction, and inform preventive strategies.
FUNDING
None.
Topics: Adult; Birth Weight; Congenital Abnormalities; Famine; Female; Fetal Macrosomia; Fetal Membranes, Premature Rupture; Herpes Simplex; Herpesvirus 2, Human; Humans; Hypertension; Hypoxia; Infant, Newborn; Infant, Small for Gestational Age; Male; Malnutrition; Maternal Age; Mood Disorders; Parity; Paternal Age; Polyhydramnios; Pregnancy; Pregnancy Complications; Pregnancy Complications, Infectious; Premature Birth; Prenatal Care; Prenatal Exposure Delayed Effects; Protective Factors; Psychotic Disorders; Risk Factors; Seasons; Stress, Psychological; Young Adult
PubMed: 32220288
DOI: 10.1016/S2215-0366(20)30057-2