|
1
|
Lee YF, Lin YH, Lin CH, Lin MC. Influenza Infection During Pregnancy and Risk of Seizures in Offspring. JAMA Netw Open 2024; 7:e2434935. [PMID: 39312238 PMCID: PMC11420688 DOI: 10.1001/jamanetworkopen.2024.34935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/25/2024] Open
Abstract
Importance Seizure is a common neurological problem among infants and children up to age 6 years. Prenatal exposure to maternal influenza infection has been reported to be associated with childhood seizures. Objective To evaluate the association between maternal influenza infection and risk of childhood seizures. Designs, Setting, and Participants This cohort study identified mother-offspring pairs from January 1, 2004, to December 31, 2013, using records in Taiwan's Maternal and Child Health Database. Mothers who had influenza infection during pregnancy and their first offspring were identified and assigned to the influenza group. Mothers in the control group were those without influenza during pregnancy and were matched 1:4 with mothers in the influenza group by maternal age, offspring sex, and date of delivery. Offspring were followed up until December 31, 2020. Data were analyzed between March 2023 and July 2024. Exposure Diagnosis of influenza infection during pregnancy defined using International Classification of Diseases, Ninth Revision, Clinical Modification codes 487.0, 487.1, and 487.8, or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes J09, J10, and J11. Main Outcomes and Measures The primary outcome was the association between maternal influenza infection during pregnancy and risk of any type of seizures during childhood, including both epilepsy and febrile seizures. Adjusted hazard ratios (AHRs) and 95% CIs were estimated using Cox proportional hazards regression models. Pregnancy-related complications were collected as covariates. Results A total of 1 316 107 mother-offspring pairs were enrolled, of whom 75 835 mothers (predominant maternal age, 25-29 years; 39 324 male offspring [51.9%]) were assigned to the influenza group and 1 240 272 were matched and assigned to the control group (n = 303 340; predominant maternal age, 30-34 years; 157 296 male offspring [51.9%]). In the influenza group, there was a slightly higher prevalence of placenta previa or abruption compared with the control group (1.6% [1241] vs 1.4% [4350]; P < .001). The cumulative risk of seizures was higher among offspring whose mothers had influenza infection. After controlling for potential confounders, the AHRs were 1.09 (95% CI, 1.05-1.14) for seizures, 1.11 (95% CI, 1.06-1.17) for febrile convulsions, and 1.04 (95% CI, 0.97-1.13) for epilepsy. In the subgroup analysis, no statistically significant differences were observed between the trimesters regarding the timing of influenza infection. Conclusions and Relevance Results of this cohort study suggest that maternal influenza infection during pregnancy was associated with an increased risk of childhood seizures, especially febrile seizures, but not epilepsy. Further studies are needed to elucidate the mechanisms underlying childhood neurological development.
Collapse
Affiliation(s)
- Yi-Feng Lee
- Children's Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yi-Hsuan Lin
- Children's Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ching-Heng Lin
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Ming-Chih Lin
- Children's Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Food and Nutrition, Providence University, Taichung, Taiwan
- School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan
| |
Collapse
|
|
2
|
Yates EF, Mulkey SB. Viral infections in pregnancy and impact on offspring neurodevelopment: mechanisms and lessons learned. Pediatr Res 2024; 96:64-72. [PMID: 38509227 PMCID: PMC11257821 DOI: 10.1038/s41390-024-03145-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Revised: 02/28/2024] [Accepted: 03/04/2024] [Indexed: 03/22/2024]
Abstract
Pregnant individuals with viral illness may experience significant morbidity and have higher rates of pregnancy and neonatal complications. With the growing number of viral infections and new viral pandemics, it is important to examine the effects of infection during pregnancy on both the gestational parent and the offspring. Febrile illness and inflammation during pregnancy are correlated with risk for autism, attention deficit/hyperactivity disorder, and developmental delay in the offspring in human and animal models. Historical viral epidemics had limited follow-up of the offspring of affected pregnancies. Infants exposed to seasonal influenza and the 2009 H1N1 influenza virus experienced increased risks of congenital malformations and neuropsychiatric conditions. Zika virus exposure in utero can lead to a spectrum of abnormalities, ranging from severe microcephaly to neurodevelopmental delays which may appear later in childhood and in the absence of Zika-related birth defects. Vertical infection with severe acute respiratory syndrome coronavirus-2 has occurred rarely, but there appears to be a risk for developmental delays in the infants with antenatal exposure. Determining how illness from infection during pregnancy and specific viral pathogens can affect pregnancy and neurodevelopmental outcomes of offspring can better prepare the community to care for these children as they grow. IMPACT: Viral infections have impacted pregnant people and their offspring throughout history. Antenatal exposure to maternal fever and inflammation may increase risk of developmental and neurobehavioral disorders in infants and children. The recent SARS-CoV-2 pandemic stresses the importance of longitudinal studies to follow pregnancies and offspring neurodevelopment.
Collapse
Affiliation(s)
- Emma F Yates
- Frank H. Netter School of Medicine at Quinnipiac University, North Haven, CT, USA
| | - Sarah B Mulkey
- Children's National Hospital, Washington, DC, USA.
- Department of Neurology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
- Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
| |
Collapse
|
|
3
|
Ou J, Dong H, Dai S, Hou Y, Wang Y, Lu X, Xun G, Xia K, Zhao J, Shen Y. Development and validation of a risk score model for predicting autism based on pre- and perinatal factors. Front Psychiatry 2024; 15:1291356. [PMID: 38435974 PMCID: PMC10904522 DOI: 10.3389/fpsyt.2024.1291356] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 01/30/2024] [Indexed: 03/05/2024] Open
Abstract
Background The use of pre- and perinatal risk factors as predictive factors may lower the age limit for reliable autism prediction. The objective of this study was to develop a clinical model based on these risk factors to predict autism. Methods A stepwise logistic regression analysis was conducted to explore the relationships between 28 candidate risk factors and autism risk among 615 Han Chinese children with autism and 615 unrelated typically developing children. The significant factors were subsequently used to create a clinical risk score model. A chi-square automatic interaction detector (CHAID) decision tree was used to validate the selected predictors included in the model. The predictive performance of the model was evaluated by an independent cohort. Results Five factors (pregnancy influenza-like illness, pregnancy stressors, maternal allergic/autoimmune disease, cesarean section, and hypoxia) were found to be significantly associated with autism risk. A receiver operating characteristic (ROC) curve indicated that the risk score model had good discrimination ability for autism, with an area under the curve (AUC) of 0.711 (95% CI=0.679-0.744); in the external validation cohort, the model showed slightly worse but overall similar predictive performance. Further subgroup analysis indicated that a higher risk score was associated with more behavioral problems. The risk score also exhibited robustness in a subgroup analysis of patients with mild autism. Conclusion This risk score model could lower the age limit for autism prediction with good discrimination performance, and it has unique advantages in clinical application.
Collapse
Affiliation(s)
- Jianjun Ou
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Huixi Dong
- Mental Health Center of Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Si Dai
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Yanting Hou
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Ying Wang
- Mental Health Center of Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Xiaozi Lu
- Qingdao Mental Health Center, Qingdao, Shandong, China
| | - Guanglei Xun
- Shandong Mental Health Center, Jinan, Shandong, China
| | - Kun Xia
- Center for Medical Genetics and School of Life Sciences, Central South University, Changsha, Hunan, China
| | - Jingping Zhao
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Yidong Shen
- Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
| |
Collapse
|
|
4
|
Hwang JW, Lee JS. Korean Clinical Guideline for Autism Spectrum Disorder - Clinical Features, Course, Epidemiology, and Cause. Soa Chongsonyon Chongsin Uihak 2024; 35:8-14. [PMID: 38204746 PMCID: PMC10774551 DOI: 10.5765/jkacap.230040] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 08/10/2023] [Accepted: 12/03/2023] [Indexed: 01/12/2024] Open
Abstract
Autism spectrum disorder (ASD) is a heterogeneous developmental disorder characterized by impairments in two core areas: 1) social communication and interaction and 2) restricted and repetitive patterns of behaviors and interests. In general, ASD is known to be a lifelong disorder. Follow-up studies from childhood to adulthood have reported that the severity of the key symptoms ASD decreases over time. However, chronic health problems including mental health occur in many patients with ASD. The prevalence of ASD has increased from around 0.04% in the 1970s to 2.8% at present. The average age of diagnosis in developed countries is 38-120 months of age. Recent evidence suggests that biological factors which include genetic, congenital, immunological, neuroanatomical, biochemical, and environmental ones are important in causing autism. Until now, early signs and various risk factors of ASD have been suggested.
Collapse
Affiliation(s)
- Jun-Won Hwang
- Department of Psychiatry, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Jeong-Seop Lee
- Department of Psychiatry, Inha University Hospital, Inha University School of Medicine, Incheon, Korea
| |
Collapse
|
|
5
|
Botsas G, Koidou E, Chatzinikolaou K, Grouios G. Environmental Influences on Individuals with Autistic Spectrum Disorders with Special Emphasis on Seasonality: An Overview. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1851. [PMID: 38136053 PMCID: PMC10742301 DOI: 10.3390/children10121851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/20/2023] [Accepted: 11/22/2023] [Indexed: 12/24/2023]
Abstract
This paper offers an in-depth exploration of the intricate relationship between environmental factors and autism spectrum disorder (ASD), with a special emphasis on seasonality. It reviews existing research, providing a comprehensive summary of findings and highlighting the multifaceted dimensions of several environmental factors influencing the etiology of ASD. The discussion encompasses various elements, including birth months, maternal health, dietary choices, and vitamin D deficiency, delving into the intricate interplay of seasonality with environmental influences such as viral infections and solar radiation. The present study raises essential questions regarding the timing of environmental influences and the factors contributing to the rising prevalence of ASD. Ultimately, it underscores the need for future epidemiological research to incorporate more extensive investigations of environmental risk factors and employ advanced statistical analyses. This comprehensive overview contributes to a deeper understanding of how environmental factors, particularly seasonality, may be linked to the occurrence of ASD and its increasing prevalence, recognizing the multifaceted and diverse nature of these interactions.
Collapse
Affiliation(s)
- George Botsas
- Department of Early Childhood and Care, School of Social Sciences, International Hellenic University, 57400 Thessaloniki, Greece
- Department of Education, School of Education and Social Sciences, Frederick University, 3080 Limassol, Cyprus
| | - Eirini Koidou
- Department of Human Performance, School of Physical Education and Sports Sciences, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece; (E.K.); (K.C.); (G.G.)
| | - Konstantinos Chatzinikolaou
- Department of Human Performance, School of Physical Education and Sports Sciences, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece; (E.K.); (K.C.); (G.G.)
| | - George Grouios
- Department of Human Performance, School of Physical Education and Sports Sciences, Aristotle University of Thessaloniki, 57001 Thessaloniki, Greece; (E.K.); (K.C.); (G.G.)
| |
Collapse
|
|
6
|
Foo D, Sarna M, Pereira G, Moore HC, Regan AK. Association between maternal influenza vaccination and neurodevelopmental disorders in childhood: a longitudinal, population-based linked cohort study. Arch Dis Child 2023; 108:647-653. [PMID: 37001967 PMCID: PMC10423464 DOI: 10.1136/archdischild-2022-324269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 03/02/2023] [Indexed: 04/07/2023]
Abstract
OBJECTIVE To assess the association between in utero exposure to seasonal inactivated influenza vaccine (IIV) and the risk of a diagnosis of a neurodevelopmental disorder in early childhood. DESIGN Retrospective cohort study. SETTING Population-based birth registry linked with health administrative databases in Western Australia (WA). PARTICIPANTS Singleton, liveborn children born between 1 April 2012 and 1 July 2016 in WA. EXPOSURE Receipt of seasonal IIV during pregnancy obtained from a state-wide antenatal vaccination database. MAIN OUTCOME MEASURES Clinical diagnosis of a neurodevelopmental disorder was recorded from hospital inpatient and emergency department records. We used Cox proportional hazard regression, weighted by the inverse-probability of treatment (vaccination), to estimate the hazard ratio (HR) of neurodevelopmental disorders associated with in utero exposure to seasonal IIV. RESULTS The study included 140 514 children of whom, 15 663 (11.2%) were exposed to seasonal IIV in utero. The prevalence of neurodevelopmental disorders was 5.4%, including mental or behavioural (0.4%), neurological (5.1%), seizure (2.2%) and sleep disorders (2.7%). Maternal IIV was not associated with increased risk of neurodevelopmental disorders (HR 1.00; 95% CI 0.91 to 1.08). Children exposed in the first trimester had a lower risk of seizure disorders (adjusted HR [aHR] 0.73; 95% CI 0.54 to 0.998), and preterm children exposed any time during pregnancy had a lower risk of sleep disorders (aHR 0.63; 95% CI 0.41 to 0.98). CONCLUSIONS We did not observe increased risk of neurodevelopmental disorders following in utero exposure to seasonal IIV. Although we observed some evidence for lower risk of seizure and sleep disorders, additional studies are required to confirm.
Collapse
Affiliation(s)
- Damien Foo
- Curtin School of Population Health, Curtin University, Perth, Western Australia, Australia
- Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia
| | - Mohinder Sarna
- Curtin School of Population Health, Curtin University, Perth, Western Australia, Australia
- Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia
| | - Gavin Pereira
- Curtin School of Population Health, Curtin University, Perth, Western Australia, Australia
- eNable Institute, Curtin University, Perth, Western Australia, Australia
| | - Hannah C Moore
- Curtin School of Population Health, Curtin University, Perth, Western Australia, Australia
- Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia
| | - Annette K Regan
- School of Nursing and Health Professions, University of San Francisco, San Francisco, California, USA
- Fielding School of Public Health, University of California Los Angeles, Los Angeles, California, USA
| |
Collapse
|
|
7
|
Al-Beltagi M, Saeed NK, Elbeltagi R, Bediwy AS, Aftab SAS, Alhawamdeh R. Viruses and autism: A Bi-mutual cause and effect. World J Virol 2023; 12:172-192. [PMID: 37396705 PMCID: PMC10311578 DOI: 10.5501/wjv.v12.i3.172] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/16/2023] [Accepted: 04/18/2023] [Indexed: 06/21/2023] Open
Abstract
Autism spectrum disorder (ASD) is a group of heterogeneous, multi-factorial, neurodevelopmental disorders resulting from genetic and environmental factors interplay. Infection is a significant trigger of autism, especially during the critical developmental period. There is a strong interplay between the viral infection as a trigger and a result of ASD. We aim to highlight the mutual relationship between autism and viruses. We performed a thorough literature review and included 158 research in this review. Most of the literature agreed on the possible effects of the viral infection during the critical period of development on the risk of developing autism, especially for specific viral infections such as Rubella, Cytomegalovirus, Herpes Simplex virus, Varicella Zoster Virus, Influenza virus, Zika virus, and severe acute respiratory syndrome coronavirus 2. Viral infection directly infects the brain, triggers immune activation, induces epigenetic changes, and raises the risks of having a child with autism. At the same time, there is some evidence of increased risk of infection, including viral infections in children with autism, due to lots of factors. There is an increased risk of developing autism with a specific viral infection during the early developmental period and an increased risk of viral infections in children with autism. In addition, children with autism are at increased risk of infection, including viruses. Every effort should be made to prevent maternal and early-life infections and reduce the risk of autism. Immune modulation of children with autism should be considered to reduce the risk of infection.
Collapse
Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Alghrabia, Egypt
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Pathology Department, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 12, Bahrain
- Microbiology Section, Pathology Department, Irish Royal College of Surgeon, Busaiteen 15503, Muharraq, Bahrain
| | - Reem Elbeltagi
- Department of Medicine, The Royal College of Surgeons in Ireland - Bahrain, Busiateen 15503, Muharraq, Bahrain
| | - Adel Salah Bediwy
- Department of Pulmonolgy, Faculty of Medicine, Tanta University, Tanta 31527, Alghrabia, Egypt
- Department of Chest Disease, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Syed A Saboor Aftab
- Endocrinology and DM, William Harvey Hospital (Paula Carr Centre), Ashford TN24 0LZ, Kent, United Kingdom
| | - Rawan Alhawamdeh
- Pediatrics Research and Development, Genomics Creativity and Play Center, Manama 0000, Bahrain
| |
Collapse
|
|
8
|
Hall MB, Willis DE, Rodriguez EL, Schwarz JM. Maternal immune activation as an epidemiological risk factor for neurodevelopmental disorders: Considerations of timing, severity, individual differences, and sex in human and rodent studies. Front Neurosci 2023; 17:1135559. [PMID: 37123361 PMCID: PMC10133487 DOI: 10.3389/fnins.2023.1135559] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Accepted: 03/13/2023] [Indexed: 05/02/2023] Open
Abstract
Epidemiological evidence suggests that one's risk of being diagnosed with a neurodevelopmental disorder (NDD)-such as autism, ADHD, or schizophrenia-increases significantly if their mother had a viral or bacterial infection during the first or second trimester of pregnancy. Despite this well-known data, little is known about how developing neural systems are perturbed by events such as early-life immune activation. One theory is that the maternal immune response disrupts neural processes important for typical fetal and postnatal development, which can subsequently result in specific and overlapping behavioral phenotypes in offspring, characteristic of NDDs. As such, rodent models of maternal immune activation (MIA) have been useful in elucidating neural mechanisms that may become dysregulated by MIA. This review will start with an up-to-date and in-depth, critical summary of epidemiological data in humans, examining the association between different types of MIA and NDD outcomes in offspring. Thereafter, we will summarize common rodent models of MIA and discuss their relevance to the human epidemiological data. Finally, we will highlight other factors that may interact with or impact MIA and its associated risk for NDDs, and emphasize the importance for researchers to consider these when designing future human and rodent studies. These points to consider include: the sex of the offspring, the developmental timing of the immune challenge, and other factors that may contribute to individual variability in neural and behavioral responses to MIA, such as genetics, parental age, the gut microbiome, prenatal stress, and placental buffering.
Collapse
|
|
9
|
Fung SG, Fakhraei R, Condran G, Regan AK, Dimanlig-Cruz S, Ricci C, Foo D, Sarna M, Török E, Fell DB. Neuropsychiatric outcomes in offspring after fetal exposure to maternal influenza infection during pregnancy: A systematic review. Reprod Toxicol 2022; 113:155-169. [PMID: 36100136 DOI: 10.1016/j.reprotox.2022.09.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 08/24/2022] [Accepted: 09/05/2022] [Indexed: 01/15/2023]
Abstract
Increasing evidence suggests that influenza infection in pregnancy may disrupt fetal neurodevelopment. The impact of maternal influenza infection on offspring neuropsychiatric health has not been comprehensively reviewed. We systematically reviewed comparative studies evaluating associations between maternal influenza infection and neuropsychiatric health outcomes in offspring. We searched MEDLINE, EMBASE, CINAHL, and Web of Science for articles published until January 7, 2022. Included were English studies evaluating neuropsychiatric outcomes in offspring aged > 6 months born to women with and without influenza during pregnancy, defined as clinical or laboratory-confirmed influenza illness, or being pregnant during pandemics/epidemics. Of 12,010 records screened, 42 studies were included. Heterogeneity in study design, exposures, and outcome definitions precluded meta-analyses. Four of 14 studies assessing schizophrenia reported adjusted ratio estimates from 0.5 to 8.2; most 95% CIs contained the null value; study quality was high in three of four. Two studies reported an increased risk of schizophrenia with influenza exposure any time during pregnancy (adjusted incidence rate ratio 8.2, 95% CI: 1.4-48.8; adjusted odds ratio 1.3, 95% CI: 1.2-1.5); another reported a reduced risk with first-trimester exposure (adjusted risk ratio 0.5, 95% CI: 0.3-0.9). Seven studies of autism spectrum disorder reported adjusted ratio estimates from 0.9 to 4.0; all 95% CIs included the null value; study quality was high in four. No conclusions could be drawn about the association between exposure to maternal influenza and neuropsychiatric outcomes due to the limited quantity and quality of available research. Large observational studies with long-term follow-up are required to investigate these associations.
Collapse
Affiliation(s)
- Stephen G Fung
- Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
| | - Romina Fakhraei
- Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada; The Ottawa Hospital Research Institute, Ottawa, ON, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada
| | | | - Annette K Regan
- School of Nursing and Health Professions, University of San Francisco, San Francisco, CA, United States; Curtin School of Population Health, Curtin University, Perth, WA, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia
| | | | | | - Damien Foo
- Curtin School of Population Health, Curtin University, Perth, WA, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia
| | - Mohinder Sarna
- Curtin School of Population Health, Curtin University, Perth, WA, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia
| | | | - Deshayne B Fell
- Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada; School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada.
| |
Collapse
|
|
10
|
Becerra-Culqui TA, Getahun D, Chiu V, Sy LS, Tseng HF. Prenatal influenza vaccination or influenza infection and autism spectrum disorder in offspring. Clin Infect Dis 2022; 75:1140-1148. [PMID: 35174388 DOI: 10.1093/cid/ciac101] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND As prenatal vaccinations continue to be given more frequently, it is important to assess long-term safety events. This study investigates the association between prenatal influenza vaccination or infection and autism spectrum disorder (ASD) risk in offspring. METHODS Retrospective cohort study of mother-child pairs with deliveries 1/1/2011-12/31/2014 at Kaiser Permanente Southern California was performed. Children >1 year were followed through 12/31/2018. Maternal influenza vaccination or infection during pregnancy was obtained from electronic health records. ASD was defined by International Classification of Diseases, 9th/10th Revision codes after age 1 year. Cox proportional hazards models estimated the crude and inverse probability of treatment weighted (IPTW) hazard ratios (HR) for the association between maternal influenza vaccination or infection and ASD. RESULTS There were 84,739 mother-child pairs included in the final analytic sample. Maternal vaccination coverage increased slightly over time, from 52.7% for 2011 births to 59.6% for 2014 births. Of the 46,257 women vaccinated, 32.4% were vaccinated during the 1 st trimester, 41.8% during the 2 nd trimester, and 25.8% during the 3 rd trimester. ASD was diagnosed in 1,930 (2.3%) children. The IPTW analyses showed no association between prenatal influenza vaccination or infection and ASD in offspring (HR: 1.04, 95% confidence interval [CI]: 0.95, 1.13; HR: 1.12, 95% CI: 0.66, 1.89, respectively). CONCLUSIONS Prenatal influenza vaccination or infection was not associated with ASD risk in offspring. The findings support recommendations to vaccinate pregnant women to protect themselves and their infants, both of whom are vulnerable to severe morbidity following infection.
Collapse
Affiliation(s)
- Tracy A Becerra-Culqui
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.,Department of Occupational Therapy, California State University, Dominguez Hills, Carson CA, USA
| | - Darios Getahun
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.,Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine School of Medicine, Pasadena, CA, USA
| | - Vicki Chiu
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA
| | - Lina S Sy
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA
| | - Hung Fu Tseng
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA.,Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine School of Medicine, Pasadena, CA, USA
| |
Collapse
|
|
11
|
Oakley LL, Regan AK, Fell DB, Spruin S, Bakken IJ, Kwong JC, Pereira G, Nassar N, Aaberg KM, Wilcox AJ, Håberg SE. Childhood seizures after prenatal exposure to maternal influenza infection: a population-based cohort study from Norway, Australia and Canada. Arch Dis Child 2022; 107:153-159. [PMID: 34187781 PMCID: PMC8908878 DOI: 10.1136/archdischild-2021-322210] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 06/10/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To assess whether clinical and/or laboratory-confirmed diagnosis of maternal influenza during pregnancy increases the risk of seizures in early childhood. DESIGN Analysis of prospectively collected registry data for children born between 2009 and 2013 in three high-income countries. We used Cox regression to estimate country-level adjusted HRs (aHRs); fixed-effects meta-analyses were used to pool adjusted estimates. SETTING Population-based. PARTICIPANTS 1 360 629 children born between 1 January 2009 and 31 December 2013 in Norway, Australia (New South Wales) and Canada (Ontario). EXPOSURE Clinical and/or laboratory-confirmed diagnosis of maternal influenza infection during pregnancy. MAIN OUTCOME MEASURES We extracted data on recorded seizure diagnosis in secondary/specialist healthcare between birth and up to 7 years of age; additional analyses were performed for the specific seizure outcomes 'epilepsy' and 'febrile seizures'. RESULTS Among 1 360 629 children in the study population, 14 280 (1.0%) were exposed to maternal influenza in utero. Exposed children were at increased risk of seizures (aHR 1.17, 95% CI 1.07 to 1.28), and also febrile seizures (aHR 1.20, 95% CI 1.07 to 1.34). There was no strong evidence of an increased risk of epilepsy (aHR 1.07, 95% CI 0.81 to 1.41). Risk estimates for seizures were higher after influenza infection during the second and third trimester than for first trimester. CONCLUSIONS In this large international study, prenatal exposure to influenza infection was associated with increased risk of childhood seizures.
Collapse
Affiliation(s)
- Laura L Oakley
- Department of Non-communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK
- Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Annette K Regan
- School of Nursing and Health Professions, University of San Francisco, San Francisco, California, USA
- School of Public Health, Curtin University, Perth, Western Australia, Australia
- Fielding School of Public Health, University of California Los Angeles, Los Angeles, California, USA
| | - Deshayne B Fell
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
- ICES, Toronto, Ontario, Canada
- Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, Ontario, Canada
| | - Sarah Spruin
- ICES, Toronto, Ontario, Canada
- Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Inger Johanne Bakken
- Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Jeffrey C Kwong
- ICES, Toronto, Ontario, Canada
- Division of Epidemiology, University of Toronto Dalla Lana School of Public Health, Toronto, Ontario, Canada
- Public Health Ontario, Toronto, Ontario, Canada
- Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada
- University Health Network, Toronto, Ontario, Canada
| | - Gavin Pereira
- School of Public Health, Curtin University, Perth, Western Australia, Australia
| | - Natasha Nassar
- Child Population and Translational Health Research, Children's Hospital at Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia
| | - Kari M Aaberg
- The National Center for Epilepsy, Oslo University Hospital, Oslo, Norway
| | - Allen J Wilcox
- Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
- Epidemiology Branch, National Institutes of Health/National Institute of Environmental Health Sciences, Durham, North Carolina, USA
| | - Siri E Håberg
- Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
| |
Collapse
|
|
12
|
Marí-Bauset S, Peraita-Costa I, Donat-Vargas C, Llopis-González A, Marí-Sanchis A, Llopis-Morales J, Morales Suárez-Varela M. Systematic review of prenatal exposure to endocrine disrupting chemicals and autism spectrum disorder in offspring. AUTISM : THE INTERNATIONAL JOURNAL OF RESEARCH AND PRACTICE 2022; 26:6-32. [PMID: 34412519 DOI: 10.1177/13623613211039950] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
LAY ABSTRACT Autism spectrum disorders comprise a complex group with many subtypes of behaviorally defined neurodevelopmental abnormalities in two core areas: deficits in social communication and fixated, restricted, repetitive, or stereotyped behaviors and interests each with potential unique risk factors and characteristics. The underlying mechanisms and the possible causes of autism spectrum disorder remain elusive and while increased prevalence is undoubtable, it is unclear if it is a reflection of diagnostic improvement or emerging risk factors such as endocrine disrupting chemicals. Epidemiological studies, which are used to study the relation between endocrine disrupting chemicals and autism spectrum disorder, can have inherent methodological challenges that limit the quality and strength of their findings. The objective of this work is to systematically review the treatment of these challenges and assess the quality and strength of the findings in the currently available literature. The overall quality and strength were "moderate" and "limited," respectively. Risk of bias due to the exclusion of potential confounding factors and the lack of accuracy of exposure assessment methods were the most prevalent. The omnipresence of endocrine disrupting chemicals and the biological plausibility of the association between prenatal exposure and later development of autism spectrum disorder highlight the need to carry out well-designed epidemiological studies that overcome the methodological challenges observed in the currently available literature in order to be able to inform public policy to prevent exposure to these potentially harmful chemicals and aid in the establishment of predictor variables to facilitate early diagnosis of autism spectrum disorder and improve long-term outcomes.
Collapse
Affiliation(s)
- Salvador Marí-Bauset
- Unit of Public Health and Environmental Care, Department of Preventive Medicine and Public Health, Food Sciences, Toxicology and Forensic Medicine, University of Valencia, Spain
| | - Isabel Peraita-Costa
- Unit of Public Health and Environmental Care, Department of Preventive Medicine and Public Health, Food Sciences, Toxicology and Forensic Medicine, University of Valencia, Spain
- CIBER in Epidemiology and Public Health (CIBERESP), Institute of Health Carlos III, Spain
| | | | - Agustín Llopis-González
- Unit of Public Health and Environmental Care, Department of Preventive Medicine and Public Health, Food Sciences, Toxicology and Forensic Medicine, University of Valencia, Spain
- CIBER in Epidemiology and Public Health (CIBERESP), Institute of Health Carlos III, Spain
| | | | - Juan Llopis-Morales
- Unit of Public Health and Environmental Care, Department of Preventive Medicine and Public Health, Food Sciences, Toxicology and Forensic Medicine, University of Valencia, Spain
| | - María Morales Suárez-Varela
- Unit of Public Health and Environmental Care, Department of Preventive Medicine and Public Health, Food Sciences, Toxicology and Forensic Medicine, University of Valencia, Spain
- CIBER in Epidemiology and Public Health (CIBERESP), Institute of Health Carlos III, Spain
| |
Collapse
|
|
13
|
Ng DQ, Dang E, Chen L, Nguyen MT, Nguyen MKN, Samman S, Nguyen TMT, Cadiz CL, Nguyen L, Chan A. Current and recommended practices for evaluating adverse drug events using electronic health records: A systematic review. JOURNAL OF THE AMERICAN COLLEGE OF CLINICAL PHARMACY 2021. [DOI: 10.1002/jac5.1524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Ding Quan Ng
- School of Pharmacy & Pharmaceutical Sciences University of California Irvine Irvine California USA
| | - Emily Dang
- School of Pharmacy & Pharmaceutical Sciences University of California Irvine Irvine California USA
| | - Lijie Chen
- School of Pharmacy & Pharmaceutical Sciences University of California Irvine Irvine California USA
| | - Mary Thuy Nguyen
- School of Pharmacy & Pharmaceutical Sciences University of California Irvine Irvine California USA
| | - Michael Ky Nguyen Nguyen
- School of Pharmacy & Pharmaceutical Sciences University of California Irvine Irvine California USA
| | - Sarah Samman
- School of Pharmacy & Pharmaceutical Sciences University of California Irvine Irvine California USA
| | - Tiffany Mai Thy Nguyen
- School of Pharmacy & Pharmaceutical Sciences University of California Irvine Irvine California USA
| | - Christine Luu Cadiz
- School of Pharmacy & Pharmaceutical Sciences University of California Irvine Irvine California USA
| | - Lee Nguyen
- School of Pharmacy & Pharmaceutical Sciences University of California Irvine Irvine California USA
| | - Alexandre Chan
- School of Pharmacy & Pharmaceutical Sciences University of California Irvine Irvine California USA
| |
Collapse
|
|
14
|
Antoun S, Ellul P, Peyre H, Rosenzwajg M, Gressens P, Klatzmann D, Delorme R. Fever during pregnancy as a risk factor for neurodevelopmental disorders: results from a systematic review and meta-analysis. Mol Autism 2021; 12:60. [PMID: 34537069 PMCID: PMC8449704 DOI: 10.1186/s13229-021-00464-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 08/06/2021] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Fever during pregnancy is a relatively common and most often trivial event. However, under specific conditions, it could affect significantly fetal brain development. Few studies, with inconsistent results, investigated whether fever, regardless the pathogen, could represent a risk factor for neurodevelopmental disorders (NDD) in the offspring. We aimed to explore further this question by performing a systematic review and meta-analysis. METHODS Peer-reviewed studies exploring the occurrence of NDD in offspring after a fetal exposure to maternal fever were included. We specifically considered the impact of fever severity and duration, taking into consideration some confounding variables such as the use of antipyretic during pregnancy, the trimester in which the fever arose, the maternal age or smoking at time of gestation. MEDLINE, EMBASE, PsycINFO, Cochrane and Web of Science were searched without language restriction. PRISMA recommendations were followed. Odds ratio (OR) were pooled using random-effects meta-analysis. Heterogeneity in effect size across studies was studied using random-effects meta-regression analysis. (PROSPERO CRD42020182801). RESULTS We finally considered ten studies gathering a total of 10,304 children with NDD. Among them, 1394 were exposed to fever during pregnancy. The selected studies were divided into 5 case-control studies and 5 cohort studies. Maternal exposure to fever during pregnancy increased the risk of NDD in offspring with an OR of 1.24 [95% CI: 1.12-1.38]. Secondary analysis revealed an increased risk for NDD when fever occurred during the first trimester of gestation [OR 1.13-95% CI: 1.02-1.26]. LIMITATIONS We excluded studies that considered infections with no evidence of fever. Another potential limitation may be the possible heterogeneity between study designs (cohorts and case-control). CONCLUSION Additional evidence supported the association between fever during pregnancy and increased risk for NDD in offspring. Careful monitoring should be considered for children born from mothers with a febrile episode during pregnancy (specifically during the first trimester).
Collapse
Affiliation(s)
- Stephanie Antoun
- Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France
| | - Pierre Ellul
- Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France
- Immunology-Immunopathology-Immunotherapy (i3), INSERM U959, Sorbonne University, Paris, France
| | - Hugo Peyre
- Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France
- Université de Paris, Inserm UMR, 1141 NeuroDiderot, Paris, France
| | - Michelle Rosenzwajg
- Immunology-Immunopathology-Immunotherapy (i3), INSERM U959, Sorbonne University, Paris, France
| | - Pierre Gressens
- Université de Paris, Inserm UMR, 1141 NeuroDiderot, Paris, France
- Centre for the Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King’s College London, King’s Health Partners, St. Thomas’ Hospital, London, UK
| | - David Klatzmann
- Immunology-Immunopathology-Immunotherapy (i3), INSERM U959, Sorbonne University, Paris, France
| | - Richard Delorme
- Child and Adolescent Psychiatry Department, Robert Debré Hospital, APHP, Paris University, Paris, France
- Human Genetics and Cognitive Functions, Institut Pasteur, Paris, France
| |
Collapse
|
|
15
|
Anashkina AA, Erlykina EI. Molecular Mechanisms of Aberrant Neuroplasticity in Autism Spectrum Disorders (Review). Sovrem Tekhnologii Med 2021; 13:78-91. [PMID: 34513070 PMCID: PMC8353687 DOI: 10.17691/stm2021.13.1.10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Indexed: 01/03/2023] Open
Abstract
This review presents the analysis and systematization of modern data on the molecular mechanisms of autism spectrum disorders (ASD) development. Polyetiology and the multifactorial nature of ASD have been proved. The attempt has been made to jointly review and systematize current hypotheses of ASD pathogenesis at the molecular level from the standpoint of aberrant brain plasticity. The mechanism of glutamate excitotoxicity formation, the effect of imbalance of neuroactive amino acids and their derivatives, neurotransmitters, and hormones on the ASD formation have been considered in detail. The strengths and weaknesses of the proposed hypotheses have been analyzed from the standpoint of evidence-based medicine. The conclusion has been drawn on the leading role of glutamate excitotoxicity as a biochemical mechanism of aberrant neuroplasticity accompanied by oxidative stress and mitochondrial dysfunction. The mechanism of aberrant neuroplasticity has also been traced at the critical moments of the nervous system development taking into account the influence of various factors of the internal and external environment. New approaches to searching for ASD molecular markers have been considered.
Collapse
Affiliation(s)
- A A Anashkina
- Senior Teacher, Department of Biochemistry named after G.Y. Gorodisskaya; Senior Researcher, Central Scientific Research Laboratory, Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Square, Nizhny Novgorod, 603005, Russia
| | - E I Erlykina
- Professor, Head of the Department of Biochemistry named after G.Y. Gorodisskaya, Privolzhsky Research Medical University, 10/1 Minin and Pozharsky Square, Nizhny Novgorod, 603005, Russia
| |
Collapse
|
|
16
|
Hanley GE, Ip A, Oberlander TF. Epidural Analgesia and Autism Spectrum Disorder Risk-The Challenges Inherent in Complex Observational Research. JAMA Pediatr 2021; 175:675-677. [PMID: 33871555 DOI: 10.1001/jamapediatrics.2021.0382] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Gillian E Hanley
- Department of Obstetrics and Gynaecology, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Angie Ip
- Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada.,School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
| | - Tim F Oberlander
- Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada.,School of Population and Public Health, The University of British Columbia, Vancouver, British Columbia, Canada
| |
Collapse
|
|
17
|
Fruit and vegetable consumption before and during pregnancy and developmental delays in offspring aged 2 years in Japan. Br J Nutr 2021; 127:1250-1258. [PMID: 34121643 PMCID: PMC8980726 DOI: 10.1017/s0007114521002154] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The association between fruit and vegetable consumption before and during pregnancy and offspring’s physical growth has been well reported, but no study has focused on offspring’s neurological development. We aimed to explore the association between maternal fruit and vegetable consumption before and during pregnancy and developmental delays in their offspring aged 2 years. Between July 2013 and March 2017, 23 406 women were recruited for the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Fruit and vegetable consumption was calculated using FFQ, and offspring’s developmental delays were evaluated by the Ages & Stages Questionnaires, Third Edition (ASQ-3) for infants aged 2 years. Finally, 10 420 women and 10 543 infants were included in the analysis. Totally, 14·9 % of children had developmental delay when screened using the ASQ-3. Women in the highest quartile of vegetable consumption from pre-pregnancy to early pregnancy and from early to mid-pregnancy had lower odds of offspring’s developmental delays (OR 0·74; 95 % CI 0·63, 0·89 and OR 0·70; 95 % CI 0·59, 0·84, respectively) than women in the lowest quartile. Women in the highest quartile of fruit consumption from early to mid-pregnancy had lower odds of offspring’s developmental delays (OR 0·78; 95 % CI 0·66, 0·92) than women in the lowest quartile. In conclusion, high fruit and vegetable consumption before and during pregnancy was associated with a lower risk of developmental delays in offspring aged 2 years.
Collapse
|
|
18
|
Mehrabadi A, Dodds L, MacDonald NE, Top KA, Benchimol EI, Kwong JC, Ortiz JR, Sprague AE, Walsh LK, Wilson K, Fell DB. Association of Maternal Influenza Vaccination During Pregnancy With Early Childhood Health Outcomes. JAMA 2021; 325:2285-2293. [PMID: 34100870 PMCID: PMC8188273 DOI: 10.1001/jama.2021.6778] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
IMPORTANCE Seasonal influenza vaccination in pregnancy can reduce influenza illness among pregnant women and newborns. Evidence is limited on whether seasonal influenza vaccination in pregnancy is associated with adverse childhood health outcomes. OBJECTIVE To assess the association between maternal influenza vaccination during pregnancy and early childhood health outcomes. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study, using a birth registry linked with health administrative data. All live births in Nova Scotia, Canada, between October 1, 2010, and March 31, 2014, were included, with follow-up until March 31, 2016. Adjusted hazard ratios (HRs) and incidence rate ratios (IRRs) with 95% confidence intervals were estimated while controlling for maternal medical history and other potential confounders using inverse probability of treatment weighting. EXPOSURES Seasonal influenza vaccination during pregnancy. MAIN OUTCOMES AND MEASURES Childhood outcomes studied were immune-related (eg, asthma, infections), non-immune-related (eg, neoplasms, sensory impairment), and nonspecific (eg, urgent or inpatient health care utilization), measured from emergency department and hospitalization databases. RESULTS Among 28 255 children (49% female, 92% born at ≥37 weeks' gestation), 10 227 (36.2%) were born to women who received seasonal influenza vaccination during pregnancy. During a mean follow-up of 3.6 years, there was no significant association between maternal influenza vaccination and childhood asthma (incidence rate, 3.0 vs 2.5 per 1000 person-years; difference, 0.53 per 1000 person-years [95% CI, -0.15 to 1.21]; adjusted HR, 1.22 [95% CI, 0.94 to 1.59]), neoplasms (0.32 vs 0.26 per 1000 person-years; difference, 0.06 per 1000 person-years [95% CI, -0.16 to 0.28]; adjusted HR, 1.26 [95% CI, 0.57 to 2.78]), or sensory impairment (0.80 vs 0.97 per 1000 person-years; difference, -0.17 per 1000 person-years [95% CI, -0.54 to 0.21]; adjusted HR, 0.82 [95% CI, 0.49 to 1.37]). Maternal influenza vaccination in pregnancy was not significantly associated with infections in early childhood (incidence rate, 184.6 vs 179.1 per 1000 person-years; difference, 5.44 per 1000 person-years [95% CI, 0.01 to 10.9]; adjusted IRR, 1.07 [95% CI, 0.99 to 1.15]) or with urgent and inpatient health services utilization (511.7 vs 477.8 per 1000 person-years; difference, 33.9 per 1000 person-years [95% CI, 24.9 to 42.9]; adjusted IRR, 1.05 [95% CI, 0.99 to 1.16]). CONCLUSIONS AND RELEVANCE In this population-based cohort study with mean follow-up duration of 3.6 years, maternal influenza vaccination during pregnancy was not significantly associated with an increased risk of adverse early childhood health outcomes.
Collapse
Affiliation(s)
- Azar Mehrabadi
- Departments of Obstetrics and Gynaecology, Dalhousie University, Halifax, Nova Scotia, Canada
- Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Linda Dodds
- Departments of Obstetrics and Gynaecology, Dalhousie University, Halifax, Nova Scotia, Canada
- Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Noni E. MacDonald
- Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Karina A. Top
- Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Eric I. Benchimol
- Department of Paediatrics and Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
- Division of Gastroenterology, Hepatology and Nutrition and Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada
- ICES, Toronto, Ontario, Canada
| | - Jeffrey C. Kwong
- ICES, Toronto, Ontario, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
- Public Health Ontario, Toronto, Ontario, Canada
- Department of Family and Community Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Justin R. Ortiz
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore
| | - Ann E. Sprague
- Better Outcomes Registry & Network, Ottawa, Ontario, Canada
- Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, Ontario, Canada
| | - Laura K. Walsh
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| | - Kumanan Wilson
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Deshayne B. Fell
- ICES, Toronto, Ontario, Canada
- Children’s Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, Ontario, Canada
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
| |
Collapse
|
|
19
|
Nwoji U. Seasonal influenza vaccine exposure in pregnancy: 5-year results from a pregnancy registry. Hum Vaccin Immunother 2021; 18:1932213. [PMID: 34082643 PMCID: PMC8920223 DOI: 10.1080/21645515.2021.1932213] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
The World Health Organization recommends that all pregnant women receive seasonal influenza vaccine. Under a post-authorization safety study protocol (NCT02148211), a pregnancy exposure registry was established in the United States to monitor spontaneously reported pregnancy outcomes in women vaccinated with GSK’s seasonal inactivated influenza vaccines (IIVs). From 1 June 2014 to 31 May 2019, 507 pregnancies were prospectively reported: 352 (69.4%) were lost to follow-up and 40 (7.9%) were ongoing. Reported outcomes for the remaining 115 were: 101 (87.8%) live births without congenital anomalies; 3 (2.6%) live births with congenital anomalies; 2 (1.7%) spontaneous abortions with no congenital anomalies; 1 (0.9%) spontaneous abortion with a congenital anomaly; 1 stillbirth with no apparent congenital anomaly; 7 (6.1%) ‘Unknown’. Results from 493 prospective reports received via worldwide spontaneous, passive surveillance showed similar outcomes. All cases with congenital anomaly were assessed as not likely/unlikely/unrelated to vaccination. Despite the limited number of cases and outcomes, no safety signal was identified. The study findings are aligned with previously published data and should be confirmed with other robust data sources.
What is the context?
The pneumococcus bacterium can cause infections of the meninges, blood, lung, middle ear and sinuses. Two vaccins, Synflorix (GSK) and Prevnar 13 (Pfizer Inc.), are widely used to protect young children against these infections. The vaccines’ compositions differ: Synflorix includes antigens from 10 pneumococcus strains (or “serotypes”) and Prevnar 13 from 13 serotypes. However, both have a similar effect on the total pneumococcal disease burden in children.
What does this commentary highlight?
This commentary summarizes the evidence beihnd the two vaccines’ comparable impact on pneumococcal disase. It also looks at why the vaccines have a similar effect on the total pneumococcal disease burden despite their different compositions.
What is the impact on current thinking?
Given that Synflorix and Prevnar 13 have a comparable impact on pneumococcal disease, a country’s choice between the two vaccines will depend on vaccine supply, cost, logistical factors (e.g., transport, storage, training requirements of health workers) and the local pneumococcal epidemiology.
Collapse
|
|
20
|
Tioleco N, Silberman AE, Stratigos K, Banerjee-Basu S, Spann MN, Whitaker AH, Turner JB. Prenatal maternal infection and risk for autism in offspring: A meta-analysis. Autism Res 2021; 14:1296-1316. [PMID: 33720503 DOI: 10.1002/aur.2499] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 02/13/2021] [Accepted: 02/21/2021] [Indexed: 12/27/2022]
Abstract
While prenatal maternal infection has received attention as a preventable and treatable risk factor for autism, findings have been inconsistent. This paper presents the results of a meta-analysis to determine whether the weight of the evidence supports such an association. Studies with a categorical diagnosis of autism as the outcome and an assessment of its association with prenatal maternal infection or fever (or the data necessary to compute this association) were included. A total of 36 studies met these criteria. Two independent reviewers extracted data on study design, methods of assessment, type of infectious agent, site of infection, trimester of exposure, definition of autism, and effect size. Analyses demonstrated a statistically significant association of maternal infection/fever with autism in offspring (OR = 1.32; 95% CI = 1.20-1.46). Adjustment for evident publication bias slightly weakened this association. There was little variation in effect sizes across agent or site of infection. Small differences across trimester of exposure were not statistically significant. There was some evidence that recall bias associated with status on the outcome variable leads to differential misclassification of exposure status. Nonetheless, the overall association is only modestly reduced when studies potentially contaminated by such bias are removed. Although causality has not been firmly established, these findings suggest maternal infection during pregnancy confers an increase in risk for autism in offspring. Given the prevalence of this risk factor, it is possible that the incidence of autism would be reduced by 12%-17% if maternal infections could be prevented or safely treated in a timely manner. LAY SUMMARY: This study is a meta-analysis of the association of maternal infection during pregnancy and subsequent autism in offspring. In combining the results from 36 studies of this association we find that a significant relationship is present. The association does not vary much across the types of infections or when they occur during pregnancy. We conclude that the incidence of autism could be substantially reduced if maternal infections could be prevented or safely treated in a timely manner.
Collapse
Affiliation(s)
- Nina Tioleco
- Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, New York, New York, USA.,Division of Child and Adolescent Psychiatry, The New York State Psychiatric Institute, New York, New York, USA
| | - Anna E Silberman
- Division of Child and Adolescent Psychiatry, The New York State Psychiatric Institute, New York, New York, USA
| | - Katharine Stratigos
- Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, New York, New York, USA
| | | | - Marisa N Spann
- Department of Psychiatry and Pediatrics, Columbia University Irving Medical Center, New York, New York, USA
| | - Agnes H Whitaker
- Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, New York, New York, USA.,Division of Child and Adolescent Psychiatry, The New York State Psychiatric Institute, New York, New York, USA
| | - J Blake Turner
- Division of Child and Adolescent Psychiatry, Columbia University Irving Medical Center, New York, New York, USA.,Division of Child and Adolescent Psychiatry, The New York State Psychiatric Institute, New York, New York, USA
| |
Collapse
|
|
21
|
Shuid AN, Jayusman PA, Shuid N, Ismail J, Kamal Nor N, Mohamed IN. Association between Viral Infections and Risk of Autistic Disorder: An Overview. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:2817. [PMID: 33802042 PMCID: PMC7999368 DOI: 10.3390/ijerph18062817] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/25/2021] [Accepted: 03/05/2021] [Indexed: 12/26/2022]
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental condition of the central nervous system (CNS) that presents with severe communication problems, impairment of social interactions, and stereotypic behaviours. Emerging studies indicate possible associations between viral infections and neurodegenerative and neurobehavioural conditions including autism. Viral infection during critical periods of early in utero neurodevelopment may lead to increased risk of autism in the offspring. This review is aimed at highlighting the association between viral infections, including viruses similar to COVID-19, and the aetiology of autism. A literature search was conducted using Pubmed, Ovid/Medline, and Google Scholar database. Relevant search terms included "rubella and autism", "cytomegalovirus and autism", "influenza virus and autism", "Zika virus and autism", "COVID-19 and autism". Based on the search terms, a total of 141 articles were obtained and studies on infants or children with congenital or perinatal viral infection and autistic behaviour were evaluated. The possible mechanisms by which viral infections could lead to autism include direct teratogenic effects and indirect effects of inflammation or maternal immune activation on the developing brain. Brain imaging studies have shown that the ensuing immune response from these viral infections could lead to disruption of the development of brain regions and structures. Hence, long-term follow up is necessary for infants whose mothers report an inflammatory event due to viral infection at any time during pregnancy to monitor for signs of autism. Research into the role of viral infection in the development of ASD may be one avenue of improving ASD outcomes in the future. Early screening and diagnosis to detect, and maybe even prevent ASD are essential to reduce the burden of this condition.
Collapse
Affiliation(s)
- Ahmad Naqib Shuid
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas 13200, Malaysia;
| | - Putri Ayu Jayusman
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia;
| | - Nazrun Shuid
- Department of Pharmacology, Faculty of Medicine, Universiti Teknologi MARA, Sg Buloh 47000, Malaysia
| | - Juriza Ismail
- Autism Research Group, Department of Pediatrics, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (J.I.); (N.K.N.)
| | - Norazlin Kamal Nor
- Autism Research Group, Department of Pediatrics, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (J.I.); (N.K.N.)
| | - Isa Naina Mohamed
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia;
| |
Collapse
|
|
22
|
Sünnetçi E, Durankuş F, Albayrak Y, Erdoğan MA, Atasoy Ö, Erbaş O. Effects of the Prenatal Administration of Tetanus Toxoid on the Sociability and Explorative Behaviors of Rat Offspring: A Preliminary Study. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE : THE OFFICIAL SCIENTIFIC JOURNAL OF THE KOREAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY 2021; 19:84-92. [PMID: 33508791 PMCID: PMC7851460 DOI: 10.9758/cpn.2021.19.1.84] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 06/21/2020] [Accepted: 06/24/2020] [Indexed: 01/05/2023]
Abstract
OBJECTIVE Autism spectrum disorder (ASD) is a severely disabling psychiatric disease characterized by impairments in communication and social skills. Although efforts have been made to explore the etiology of ASD, its pathophysiology remains unclear. This issue is rendered more challenging by confounding data about the effects of vaccination on disease etiology. In this study, therefore, we investigated the neurodevelopmental effects of maternal tetanus toxoid administration on rat offspring. We hypothesized that the vaccine affects the sociability and preference for social novelty of rat offspring as well as the production of immunological and neurotrophic factors, including tumor necrosis factor-alfa (TNF-α), neuregulin-1 (NRG-1), neuron growth factor (NGF), and oxytocin. METHODS The study involved 12 female and 4 male adult Sprague-Dawley rats (238 ± 10 g), which were assigned to two groups. Group 1 (control group) was given 0.5 ml of normal saline (0.9% NaCl) on the 10th day of pregnancy, whereas Group 2 (experimental group) was administered 0.5 ml of tetanus vaccine (tetanus toxoid, 40 IU). RESULTS Maternal tetanus toxoid administration exerted beneficial effects on the sociability and explorative behaviors of the rats. The brain tissue levels of TNF-α, NGF, NRG-1, and oxytocin were higher in the experimental group than those among the controls. All these significant differences were found in both the male and female rats. CONCLUSION This study is the first to demonstrate the advantages of tetanus toxoid administration in relation to the sociability and explorative behaviors of rat offspring. The results showed that the vaccine also influences NRG-1, neuregulin, and oxytocin production.
Collapse
Affiliation(s)
- Eda Sünnetçi
- Department of Pediatrics, Istanbul Training and Education Hospital, Istanbul, Turkey
| | - Ferit Durankuş
- Department of Pediatrics, Istanbul Medeniyet University, Istanbul, Turkey
| | - Yakup Albayrak
- Department of Psychiatry, Faculty of Medicine, Tekirdağ Namık Kemal University, Tekirdağ, Izmir, Turkey
| | - Mümin Alper Erdoğan
- Department of Physiology, Katip Çelebi University Medical School, Izmir, Turkey
| | - Özüm Atasoy
- Department of Radiation Oncolgy, Kartal Education and Research Hospital, Istanbul, Turkey
| | - Oytun Erbaş
- Department of Physiology, Demiroğlu Bilim University Medical School, Istanbul, Turkey
| |
Collapse
|
|
23
|
Gordon-Lipkin E, Hoon A, Pardo CA. Prenatal cytomegalovirus, rubella, and Zika virus infections associated with developmental disabilities: past, present, and future. Dev Med Child Neurol 2021; 63:135-143. [PMID: 33084055 PMCID: PMC7785600 DOI: 10.1111/dmcn.14682] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/13/2020] [Indexed: 11/28/2022]
Abstract
Prenatal infections have long been recognized as important, preventable causes of developmental disabilities. The list of pathogens that are recognized to have deleterious effects on fetal brain development continues to grow, most recently with the association between Zika virus (ZIKV) and microcephaly. To answer clinical questions in real time about the impact of a novel infection on developmental disabilities, an historical framework is key. The lessons learned from three historically important pathogens: rubella, cytomegalovirus, and ZIKV, and how these lessons are useful to approach emerging congenital infections are discussed in this review. Congenital infections are preventable causes of developmental disabilities and several public health approaches may be used to prevent prenatal infection. When they cannot be prevented, the sequelae of prenatal infection may be treatable. WHAT THIS PAPER ADDS: The list of prenatal infections associated with developmental disabilities continues to increase. Lessons learned from rubella, cytomegalovirus, and Zika virus have implications for new pathogens. Severity of illness in the mother does not correlate with severity of sequelae in the infant.
Collapse
Affiliation(s)
- Eliza Gordon-Lipkin
- Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland, USA
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Alexander Hoon
- Department of Neurology and Developmental Medicine, Kennedy Krieger Institute, Baltimore, Maryland, USA
| | - Carlos A Pardo
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| |
Collapse
|
|
24
|
Khatami M. Deceptology in cancer and vaccine sciences: Seeds of immune destruction-mini electric shocks in mitochondria: Neuroplasticity-electrobiology of response profiles and increased induced diseases in four generations - A hypothesis. Clin Transl Med 2020; 10:e215. [PMID: 33377661 PMCID: PMC7749544 DOI: 10.1002/ctm2.215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 10/08/2020] [Accepted: 10/13/2020] [Indexed: 12/16/2022] Open
Abstract
From Rockefeller's support of patent medicine to Gates' patent vaccines, medical establishment invested a great deal in intellectual ignorance. Through the control over medical education and research it has created a public illusion to prop up corporate profit and encouraged the lust for money and power. An overview of data on cancer and vaccine sciences, the status of Americans' health, a survey of repeated failed projects, economic toxicity, and heavy drug consumption or addiction among young and old provide compelling evidence that in the twentieth century nearly all classic disease categories (congenital, inheritance, neonatal, or induced) shifted to increase induced diseases. Examples of this deceptology in ignoring or minimizing, and mocking fundamental discoveries and theories in cancer and vaccine sciences are attacks on research showing that (a), effective immunity is responsible for defending and killing pathogens and defective cancerous cells, correcting and repairing genetic mutations; (b) viruses cause cancer; and (c), abnormal gene mutations are often the consequences of (and secondary to) disturbances in effective immunity. The outcomes of cancer reductionist approaches to therapies reveal failure rates of 90% (+/-5) for solid tumors; loss of over 50 million lives and waste of $30-50 trillions on too many worthless, out-of-focus, and irresponsible projects. Current emphasis on vaccination of public with pathogen-specific vaccines and ingredients seems new terms for drugging young and old. Cumulative exposures to low level carcinogens and environmental hazards or high energy electronic devices (EMF; 5G) are additional triggers to vaccine toxicities (antigen-mitochondrial overload) or "seeds of immune destruction" that create mini electrical shocks (molecular sinks holes) in highly synchronized and regulated immune network that retard time-energy-dependent biorhythms in organs resulting in causes, exacerbations or consequences of mild, moderate or severe immune disorders. Four generations of drug-dependent Americans strongly suggest that medical establishment has practiced decades of intellectual deception through its claims on "war on cancer"; that cancer is 100, 200, or 1000 diseases; identification of "individual" genetic mutations to cure diseases; "vaccines are safe". Such immoral and unethical practices, along with intellectual harassment and bullying, censoring or silencing of independent and competent professionals ("Intellectual Me Too") present grave concerns, far greater compared with the sexual harassment of 'Me Too' movement that was recently spearheaded by NIH. The principal driving forces behind conducting deceptive and illogical medical/cancer and vaccine projects seem to be; (a) huge return of investment and corporate profit for selling drugs and vaccines; (b) maintenance of abusive power over public health; (c) global control of population growth via increased induction of diseases, infertility, decline in life-span, and death. An overview of accidental discoveries that we established and extended since 1980s, on models of acute and chronic ocular inflammatory diseases, provides series of the first evidence for a direct link between inflammation and multistep immune dysfunction in tumorigenesis and angiogenesis. Results are relevant to demonstrate that current emphasis on vaccinating the unborn, newborn, or infant would induce immediate or long-term immune disorders (eg, low birth weight, preterm birth, fatigue, autism, epilepsy/seizures, BBB leakage, autoimmune, neurodegenerative or digestive diseases, obesity, diabetes, cardiovascular problems, or cancers). Vaccination of the unborn is likely to disturb trophoblast-embryo-fetus-placenta biology and orderly growth of embryo-fetus, alter epithelial-mesenchymal transition or constituent-inducible receptors, damage mitochondria, and diverse function of histamine-histidine pathways. Significant increased in childhood illnesses are likely due to toxicities of vaccine and incipient (eg, metals [Al, Hg], detergents, fetal tissue, DNA/RNA) that retard bioenergetics of mitochondria, alter polarization-depolarization balance of tumoricidal (Yin) and tumorigenic (Yang) properties of immunity. Captivated by complex electobiology of immunity, this multidisciplinary perspective is an attempt to initiate identifying bases for increased induction of immune disorders in three to four generations in America. We hypothesize that (a) gene-environment-immune biorhythms parallel neuronal function (brain neuroplasticity) with super-packages of inducible (adaptive or horizontal) electronic signals and (b) autonomic sympathetic and parasympathetic circuitry that shape immunity (Yin-Yang) cannot be explained by limited genomics (innate, perpendicular) that conventionally explain certain inherited diseases (eg, sickle cell anemia, progeria). Future studies should focus on deep learning of complex electrobiology of immunity that requires differential bioenergetics from mitochondria and cytoplasm. Approaches to limit or control excessive activation of gene-environment-immunity are keys to assess accurate disease risk formulations, prevent inducible diseases, and develop universal safe vaccines that promote health, the most basic human right.
Collapse
Affiliation(s)
- Mahin Khatami
- Inflammation, Aging and Cancer, National Cancer Institute (NCI)the National Institutes of Health (NIH) (Retired)BethesdaMarylandUSA
| |
Collapse
|
|
25
|
Zerbo O, Ray GT, Zhang L, Goddard K, Fireman B, Adams A, Omer S, Kulldorff M, Klein NP. Individual and Neighborhood Factors Associated With Failure to Vaccinate Against Influenza During Pregnancy. Am J Epidemiol 2020; 189:1379-1388. [PMID: 32735018 PMCID: PMC7604527 DOI: 10.1093/aje/kwaa165] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 07/27/2020] [Accepted: 07/28/2020] [Indexed: 12/18/2022] Open
Abstract
Uptake of influenza vaccine among pregnant women remains low. We investigated whether unvaccinated pregnant women were clustered geographically and determined factors associated with failure to vaccinate using spatial and multivariate logistic regression analyses. Pregnant women who were members of Kaiser Permanente Northern California in 2015 or 2016 were included in the study. More than half (53%) of the 77,607 included pregnant women were unvaccinated. Spatial analysis identified 5 clusters with a high prevalence of unvaccinated pregnant women. The proportion of unvaccinated women ranged from 57% to 75% within clusters as compared with 51% outside clusters. In covariate-adjusted analyses, residence in a cluster was associated with a 41% increase in the odds of being unvaccinated (odds ratio (OR) = 1.41, 95% confidence interval (CI): 1.36, 1.46). The odds of being unvaccinated were greater for Black women (OR = 1.58, 95% CI: 1.49, 1.69), Hispanic women (OR = 1.15, 95% CI: 1.05, 1.25), women with subsidized health insurance (OR = 1.18, 95% CI: 1.11, 1.24), women with fewer than 5 prenatal-care visits (OR = 1.85, 95% CI: 1.60, 2.16), and neighborhoods with a high deprivation index (fourth quartile vs. first: OR = 1.14, 95% CI: 1.07, 1.21). In conclusion, unvaccinated pregnant women were clustered geographically and by key sociodemographic factors. These findings suggest that interventions to increase influenza vaccine coverage among pregnant women are needed, particularly in vulnerable populations.
Collapse
Affiliation(s)
- Ousseny Zerbo
- Correspondence to Dr. Ousseny Zerbo, Kaiser Permanente Northern California Vaccine Study Center, 1 Kaiser Plaza, 16th Floor, Oakland, CA 94612 (e-mail: )
| | | | | | | | | | | | | | | | | |
Collapse
|
|
26
|
Ludvigsson JF, Winell H, Sandin S, Cnattingius S, Stephansson O, Pasternak B. Maternal Influenza A(H1N1) Immunization During Pregnancy and Risk for Autism Spectrum Disorder in Offspring : A Cohort Study. Ann Intern Med 2020; 173:597-604. [PMID: 32866418 DOI: 10.7326/m20-0167] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND There are concerns that influenza vaccine exposure during pregnancy may be associated with increased risk for autism spectrum disorder (ASD). OBJECTIVE To examine the risk for ASD in offspring of mothers who were vaccinated against influenza A(H1N1)pdm09 ("swine flu") during pregnancy. DESIGN Population-based cohort study using nationwide registers. SETTING Seven health care regions in Sweden. PARTICIPANTS Live births between October 2009 and September 2010, with follow-up through December 2016. In total, 39 726 infants were prenatally exposed to H1N1 vaccine (13 845 during the first trimester) and 29 293 infants were unexposed. MEASUREMENTS Cox regression was used to estimate hazard ratios (HRs) for the primary outcome, ASD, before and after adjustment for potential confounders. The secondary outcome was autistic disorder (AD). RESULTS Mean follow-up was 6.7 years in both unexposed and exposed children. During follow-up, 394 (1.0%) vaccine-exposed and 330 (1.1%) unexposed children had a diagnosis of ASD. In adjusted analyses, prenatal exposure to H1N1 vaccination was not associated with a later diagnosis of ASD (adjusted HR [aHR], 0.95 [95% CI, 0.81 to 1.12]) or AD (aHR, 0.96 [CI, 0.80 to 1.16]). The 6-year standardized cumulative incidence difference between the unexposed and exposed children was 0.04% (CI, -0.09% to 0.17%) for ASD and 0.02% (CI, -0.09% to 0.14%) for AD. Restricting the analysis to vaccination in the first trimester of pregnancy did not influence risk estimates (aHR, 0.92 [CI, 0.74 to 1.16] for ASD and 0.91 [CI, 0.70 to 1.18] for AD). LIMITATION Data on H1N1 influenza infection are lacking. CONCLUSION This large cohort study found no association between maternal H1N1 vaccination during pregnancy and risk for ASD in the offspring. PRIMARY FUNDING SOURCE Swedish Research Council.
Collapse
Affiliation(s)
- Jonas F Ludvigsson
- Karolinska Institutet, Stockholm, and Örebro University Hospital, Örebro, Sweden, School of Medicine, University of Nottingham, Nottingham, United Kingdom, and Celiac Disease Center, Columbia University College of Physicians and Surgeons, New York, New York (J.F.L.)
| | - Henric Winell
- Karolinska Institutet, Stockholm, and Uppsala University, Uppsala, Sweden (H.W.)
| | - Sven Sandin
- Karolinska Institutet, Stockholm, Sweden, and Icahn School of Medicine at Mount Sinai and Seaver Autism Center for Research and Treatment at Mount Sinai, New York, New York (S.S.)
| | | | - Olof Stephansson
- Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden (O.S.)
| | - Björn Pasternak
- Karolinska Institutet, Stockholm, Sweden, and Statens Serum Institut, Copenhagen, Denmark (B.P.)
| |
Collapse
|
|
27
|
Foo DYP, Sarna M, Pereira G, Moore HC, Fell DB, Regan AK. Early Childhood Health Outcomes Following In Utero Exposure to Influenza Vaccines: A Systematic Review. Pediatrics 2020; 146:peds.2020-0375. [PMID: 32719088 DOI: 10.1542/peds.2020-0375] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/07/2020] [Indexed: 11/24/2022] Open
Abstract
CONTEXT Vaccination during pregnancy is an effective strategy for preventing infant disease; however, little is known about early childhood health after maternal vaccination. OBJECTIVES To systematically review the literature on early childhood health associated with exposure to influenza vaccines in utero. DATA SOURCES We searched CINAHL Plus, Embase, Medline, Scopus, and Web of Science for relevant articles published from inception to July 24, 2019. STUDY SELECTION We included studies published in English reporting original data with measurement of in utero exposure to influenza vaccines and health outcomes among children <5 years of age. DATA EXTRACTION Two authors independently assessed eligibility and extracted data on study design, setting, population, vaccines, outcomes, and results. RESULTS The search yielded 3647 records, of which 9 studies met the inclusion criteria. Studies examined infectious, atopic, autoimmune, and neurodevelopmental outcomes, and all-cause morbidity and mortality. Authors of 2 studies reported an inverse association between pandemic influenza vaccination and upper respiratory tract infections, gastrointestinal infections, and all-cause hospitalizations; and authors of 2 studies reported modest increased association between several childhood disorders and pandemic or seasonal influenza vaccination, which, after adjusting for confounding and multiple comparisons, were not statistically significant. LIMITATIONS Given the small number of studies addressing similarly defined outcomes, meta-analyses were deemed not possible. CONCLUSIONS Results from the few studies in which researchers have examined outcomes in children older than 6 months of age did not identify an association between exposure to influenza vaccines in utero and adverse childhood health outcomes.
Collapse
Affiliation(s)
- Damien Y P Foo
- School of Public Health, Curtin University, Perth, Western Australia, Australia; .,Wesfarmers Centre of Vaccines & Infectious Diseases
| | - Mohinder Sarna
- School of Public Health, Curtin University, Perth, Western Australia, Australia.,Wesfarmers Centre of Vaccines & Infectious Diseases
| | - Gavin Pereira
- School of Public Health, Curtin University, Perth, Western Australia, Australia.,Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia.,Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway
| | | | - Deshayne B Fell
- School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.,Children's Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada; and
| | - Annette K Regan
- School of Public Health, Curtin University, Perth, Western Australia, Australia.,Wesfarmers Centre of Vaccines & Infectious Diseases.,School of Public Health, Texas A&M University, College Station, Texas
| |
Collapse
|
|
28
|
Daaboul J, Tamouza R, Leboyer M. [Immunopsychiatry and SARS-CoV-2 pandemic: Links and possible consequences]. Encephale 2020; 47:151-156. [PMID: 32928535 PMCID: PMC7373027 DOI: 10.1016/j.encep.2020.07.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 07/20/2020] [Indexed: 12/28/2022]
Abstract
OBJECTIVE The SARS-CoV-2 (or COVID-19) pandemic has been propagating since December 2019, inducing a drastic increase in the prevalence of anxious and depressive disorders in the general population. Psychological trauma can partly explain these disorders. However, since psychiatric disorders also have an immuno-inflammatory component, the direct effects of the virus on the host's immune system, with a marked inflammatory response, but also the secondary inflammation to these psychosocial stressors, may cause the apparition or the worsening of psychiatric disorders. We describe here the probable immunopsychiatric consequences of the SARS-CoV-2 pandemic, to delineate possible screening actions and care that could be planned. METHOD Data from previous pandemics, and existing data on the psychopathological consequences of the SARS-CoV-2 pandemic, allowed us to review the possible immunopsychiatric consequences of the SARS-CoV-2 pandemic, on the gestational environment, with the risk of consecutive neurodevelopmental disorders for the fetus on one hand, on the children and adults directly infected being at increased risks of psychiatric disorders on the other hand. RESULTS As in previous pandemics, the activation of the immune system due to psychological stress and/or to infection during pregnancy, might lead to an increased risk of neurodevelopmental disorders for the fetus (schizophrenia and autism spectrum disorders). Furthermore, in individuals exposed to psychological trauma and/or infected by the virus, the risk of psychiatric disorders, especially mood disorders, is probably increased. CONCLUSION In this context, preventive measures and specialized care are necessary. Thus, it is important to propose a close follow-up to the individuals who have been infected by the virus, in order to set up the earliest care possible. Likewise, in pregnant women, screening of mood disorders during the pregnancy or the postpartum period must be facilitated. The follow-up of the babies born during the pandemic must be strengthened to screen and care for possible neurodevelopmental disorders.
Collapse
Affiliation(s)
- J Daaboul
- Université de Lille, CHU de Lille, Lille, France; DMU IMPACT, département médico-universitaire de psychiatrie et d'addictologie du groupe hospitalier universitaire Henri-Mondor, AP-HP, Créteil, France
| | - R Tamouza
- DMU IMPACT, département médico-universitaire de psychiatrie et d'addictologie du groupe hospitalier universitaire Henri-Mondor, AP-HP, Créteil, France; Fondation FondaMental, Créteil, France; Université Paris Est Créteil, UPEC, Inserm, U955, équipe 15 neuro-psychiatrie translationnelle, Institut Mondor de Recherche Biomédicale, IMRB, Créteil, France
| | - M Leboyer
- DMU IMPACT, département médico-universitaire de psychiatrie et d'addictologie du groupe hospitalier universitaire Henri-Mondor, AP-HP, Créteil, France; Fondation FondaMental, Créteil, France; Université Paris Est Créteil, UPEC, Inserm, U955, équipe 15 neuro-psychiatrie translationnelle, Institut Mondor de Recherche Biomédicale, IMRB, Créteil, France.
| |
Collapse
|
|
29
|
Hooker BS, Miller NZ. Analysis of health outcomes in vaccinated and unvaccinated children: Developmental delays, asthma, ear infections and gastrointestinal disorders. SAGE Open Med 2020; 8:2050312120925344. [PMID: 32537156 PMCID: PMC7268563 DOI: 10.1177/2050312120925344] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 04/20/2020] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE The aim of this study was to compare the health of vaccinated versus unvaccinated pediatric populations. METHODS Using data from three medical practices in the United States with children born between November 2005 and June 2015, vaccinated children were compared to unvaccinated children during the first year of life for later incidence of developmental delays, asthma, ear infections and gastrointestinal disorders. All diagnoses utilized International Classification of Diseases-9 and International Classification of Diseases-10 codes through medical chart review. Subjects were a minimum of 3 years of age, stratified based on medical practice, year of birth and gender and compared using a logistic regression model. RESULTS Vaccination before 1 year of age was associated with increased odds of developmental delays (OR = 2.18, 95% CI 1.47-3.24), asthma (OR = 4.49, 95% CI 2.04-9.88) and ear infections (OR = 2.13, 95% CI 1.63-2.78). In a quartile analysis, subjects were grouped by number of vaccine doses received in the first year of life. Higher odds ratios were observed in Quartiles 3 and 4 (where more vaccine doses were received) for all four health conditions considered, as compared to Quartile 1. In a temporal analysis, developmental delays showed a linear increase as the age cut-offs increased from 6 to 12 to 18 to 24 months of age (ORs = 1.95, 2.18, 2.92 and 3.51, respectively). Slightly higher ORs were also observed for all four health conditions when time permitted for a diagnosis was extended from ⩾ 3 years of age to ⩾ 5 years of age. CONCLUSION In this study, which only allowed for the calculation of unadjusted observational associations, higher ORs were observed within the vaccinated versus unvaccinated group for developmental delays, asthma and ear infections. Further study is necessary to understand the full spectrum of health effects associated with childhood vaccination.
Collapse
Affiliation(s)
- Brian S Hooker
- Department of Sciences and Mathematics,
Simpson University, Redding, CA, USA
| | - Neil Z Miller
- Institute of Medical and Scientific
Inquiry, Santa Fe, NM, USA
| |
Collapse
|
|
30
|
Pu Y, Yang J, Chang L, Qu Y, Wang S, Zhang K, Xiong Z, Zhang J, Tan Y, Wang X, Fujita Y, Ishima T, Wang D, Hwang SH, Hammock BD, Hashimoto K. Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase. Proc Natl Acad Sci U S A 2020; 117:11753-11759. [PMID: 32398374 PMCID: PMC7260984 DOI: 10.1073/pnas.1922287117] [Citation(s) in RCA: 101] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Epidemiological studies suggest that exposure to herbicides during pregnancy might increase risk for autism spectrum disorder (ASD) in offspring. However, the precise mechanisms underlying the risk of ASD by herbicides such as glyphosate remain unclear. Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids is shown to play a key role in the development of ASD in offspring after maternal immune activation. Here, we found ASD-like behavioral abnormalities in juvenile offspring after maternal exposure to high levels of formulated glyphosate. Furthermore, we found higher levels of sEH in the prefrontal cortex (PFC), hippocampus, and striatum of juvenile offspring, and oxylipin analysis showed decreased levels of epoxy-fatty acids such as 8 (9)-EpETrE in the blood, PFC, hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure, supporting increased activity of sEH in the offspring. Moreover, we found abnormal composition of gut microbiota and short-chain fatty acids in fecal samples of juvenile offspring after maternal glyphosate exposure. Interestingly, oral administration of TPPU (an sEH inhibitor) to pregnant mothers from E5 to P21 prevented ASD-like behaviors such as social interaction deficits and increased grooming time in the juvenile offspring after maternal glyphosate exposure. These findings suggest that maternal exposure to high levels of glyphosate causes ASD-like behavioral abnormalities and abnormal composition of gut microbiota in juvenile offspring, and that increased activity of sEH might play a role in ASD-like behaviors in offspring after maternal glyphosate exposure. Therefore, sEH may represent a target for ASD in offspring after maternal stress from occupational exposure to contaminants.
Collapse
Affiliation(s)
- Yaoyu Pu
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan
| | - Jun Yang
- Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center, University of California, Davis, CA 95616
| | - Lijia Chang
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan
| | - Youge Qu
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan
| | - Siming Wang
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan
| | - Kai Zhang
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan
| | - Zhongwei Xiong
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan
| | - Jiancheng Zhang
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan
| | - Yunfei Tan
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan
| | - Xingming Wang
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan
| | - Yuko Fujita
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan
| | - Tamaki Ishima
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan
| | - Debin Wang
- Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center, University of California, Davis, CA 95616
| | - Sung Hee Hwang
- Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center, University of California, Davis, CA 95616
| | - Bruce D Hammock
- Department of Entomology and Nematology and UC Davis Comprehensive Cancer Center, University of California, Davis, CA 95616
| | - Kenji Hashimoto
- Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 260-8670 Chiba, Japan;
| |
Collapse
|
|
31
|
Kępińska AP, Iyegbe CO, Vernon AC, Yolken R, Murray RM, Pollak TA. Schizophrenia and Influenza at the Centenary of the 1918-1919 Spanish Influenza Pandemic: Mechanisms of Psychosis Risk. Front Psychiatry 2020; 11:72. [PMID: 32174851 PMCID: PMC7054463 DOI: 10.3389/fpsyt.2020.00072] [Citation(s) in RCA: 107] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 01/28/2020] [Indexed: 12/13/2022] Open
Abstract
Associations between influenza infection and psychosis have been reported since the eighteenth century, with acute "psychoses of influenza" documented during multiple pandemics. In the late 20th century, reports of a season-of-birth effect in schizophrenia were supported by large-scale ecological and sero-epidemiological studies suggesting that maternal influenza infection increases the risk of psychosis in offspring. We examine the evidence for the association between influenza infection and schizophrenia risk, before reviewing possible mechanisms via which this risk may be conferred. Maternal immune activation models implicate placental dysfunction, disruption of cytokine networks, and subsequent microglial activation as potentially important pathogenic processes. More recent neuroimmunological advances focusing on neuronal autoimmunity following infection provide the basis for a model of infection-induced psychosis, potentially implicating autoimmunity to schizophrenia-relevant protein targets including the N-methyl-D-aspartate receptor. Finally, we outline areas for future research and relevant experimental approaches and consider whether the current evidence provides a basis for the rational development of strategies to prevent schizophrenia.
Collapse
Affiliation(s)
- Adrianna P. Kępińska
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Conrad O. Iyegbe
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Anthony C. Vernon
- Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
- MRC Centre for Neurodevelopmental Disorders, King’s College London, London, United Kingdom
| | - Robert Yolken
- Stanley Laboratory of Developmental Neurovirology, Johns Hopkins Medical Center, Baltimore, MD, United States
| | - Robin M. Murray
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| | - Thomas A. Pollak
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom
| |
Collapse
|
|
32
|
Bickford CD, Oberlander TF, Lanphear NE, Weikum WM, Janssen PA, Ouellette-Kuntz H, Hanley GE. Identification of Pediatric Autism Spectrum Disorder Cases Using Health Administrative Data. Autism Res 2019; 13:456-463. [PMID: 31799770 DOI: 10.1002/aur.2252] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 09/26/2019] [Accepted: 11/11/2019] [Indexed: 12/31/2022]
Abstract
Administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases in epidemiological studies. However, validation studies on this mode of case ascertainment have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We report on the diagnostic accuracy of using readily available health administrative data for pediatric ASD case ascertainment. The validation cohort included almost all the ASD-positive children born in British Columbia, Canada from April 1, 2000 to December 31, 2009 and consisted of 8,670 children in total. 4,079 ASD-positive and 2,787 ASD-negative children were identified using Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R) assessments done through the British Columbia Autism Assessment Network (BCAAN). An additional 1,804 ADOS/ADI-R assessed ASD-positive children were identified using Ministry of Education records. This prospectively collected clinical data (the diagnostic gold standard) was then linked to each child's physician billing and hospital discharge data. The diagnostic accuracy of 11 algorithms that used the administrative data to assign ASD case status was assessed. For all algorithms, high positive predictive values (PPVs) were observed alongside low values for other measures of diagnostic accuracy illustrating that PPVs alone are not an adequate measure of diagnostic accuracy. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders. Utilizing these data may result in misclassification bias. Methodologically sound, region-specific validation studies are needed to support the use of administrative data for ASD case ascertainment. Autism Res 2020, 13: 456-463. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Health administrative data are frequently used to identify Autism Spectrum Disorder (ASD) cases for research purposes. However, previous validation studies on this sort of case identification have lacked access to high-quality clinical diagnostic data and have not followed published reporting guidelines. We show that British Columbia's health administrative data cannot reliably be used to discriminate between children with ASD and children with other developmental disorders.
Collapse
Affiliation(s)
- Celeste D Bickford
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada
| | - Tim F Oberlander
- Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.,Sunny Hill Health Centre for Children, BC Children's Hospital, Vancouver, British Columbia, Canada.,BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada
| | - Nancy E Lanphear
- Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.,Sunny Hill Health Centre for Children, BC Children's Hospital, Vancouver, British Columbia, Canada
| | - Whitney M Weikum
- Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.,Sunny Hill Health Centre for Children, BC Children's Hospital, Vancouver, British Columbia, Canada
| | - Patricia A Janssen
- School of Population and Public Health, University of British Columbia, Vancouver, British Columbia, Canada.,BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada
| | | | - Gillian E Hanley
- BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.,Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, British Columbia, Canada
| |
Collapse
|
|
33
|
Regan AK, Håberg SE, Fell DB. Current Perspectives on Maternal Influenza Immunization. CURRENT TROPICAL MEDICINE REPORTS 2019. [DOI: 10.1007/s40475-019-00188-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
|
|
34
|
Jeong S, Jang EJ, Jo J, Jang S. Effects of maternal influenza vaccination on adverse birth outcomes: A systematic review and Bayesian meta-analysis. PLoS One 2019; 14:e0220910. [PMID: 31412058 PMCID: PMC6693758 DOI: 10.1371/journal.pone.0220910] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 07/25/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Although pregnant women are a priority group for influenza vaccination, its effect on birth outcomes has long been debated. Numerous observational studies and a few randomized controlled studies have been conducted, with inconsistent results. OBJECTIVES To evaluate the association of influenza vaccination in pregnancy with adverse birth outcomes. DATA SOURCE The Cochrane Library, PubMed, EMBASE, Web of Science, and Scopus were searched. STUDY ELIGIBILITY CRITERIA This analysis included randomized placebo-controlled studies, cohort studies, and case-control studies, in which inactivated influenza vaccination was given during pregnancy and fetal adverse birth outcomes were assessed. PARTICIPANTS & INTERVENTION Women who received inactivated influenza vaccine during pregnancy and their offspring. STUDY APPRAISAL AND SYNTHESIS Two independent reviewers and a third reviewer collaborated in study selection and data extraction. A Bayesian 3-level random-effects model was utilized to assess the impact of maternal influenza vaccination on birth outcomes, which were presented as odds ratios (ORs) with 95% credible interval (CrIs). Bayesian outcome probabilities (P) of an OR<1 were calculated, and values of at least 90% (0.9) were deemed to indicate a significant result. RESULTS Among the 6,249 identified publications, 48 studies were eligible for the meta-analysis, including 2 randomized controlled trials, 41 cohort studies, and 5 case-control studies. The risk of none of the following adverse birth outcomes decreased significantly: preterm birth (OR = 0.945, 95% CrI: 0.736-1.345, P = 73.3%), low birth weight (OR = 0.928, 95% CrI: 0.432-2.112, P = 76.7%), small for gestational age (OR = 0.971, 95% CrI: 0.249-4.217,P = 63.3%), congenital malformation (OR = 1.026, 95% CrI: 0.687-1.600, P = 38.0%), and fetal death (OR = 0.942, 95% CrI: 0.560-1.954, P = 61.6%). Summary estimates including only cohort studies showed significantly decreased risks for preterm birth, small for gestational age and fetal death. However, after adjusting for season at the time of vaccination and countries' income level, only fetal death remained significant. CONCLUSION This Bayesian meta-analysis did not find a protective effect of maternal influenza vaccination against adverse birth outcomes, as reported in previous studies. In fact, our results showed evidence of null associations between maternal influenza vaccination and adverse birth outcomes.
Collapse
Affiliation(s)
- Sohyun Jeong
- Hinda and Arthur Marcus Institute for Aging Research, Hebrew SeniorLife and Harvard Medical School, Boston, Massachusetts, United States of America
- School of Pharmacy, Sungkyunkwan University, Jangan-gu, Suwon, Gyeonggi-do, Korea
| | - Eun Jin Jang
- Department of Information Statistics, Andong National University, Gyeongsangbuk-do, Korea
| | - Junwoo Jo
- Department of Statistics, Kyungpook National University, Bukgu, Daegu, Korea
| | - Sunmee Jang
- College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon, Korea
| |
Collapse
|
|
35
|
Croen LA, Qian Y, Ashwood P, Zerbo O, Schendel D, Pinto-Martin J, Daniele Fallin M, Levy S, Schieve LA, Yeargin-Allsopp M, Sabourin KR, Ames JL. Infection and Fever in Pregnancy and Autism Spectrum Disorders: Findings from the Study to Explore Early Development. Autism Res 2019; 12:1551-1561. [PMID: 31317667 DOI: 10.1002/aur.2175] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 06/26/2019] [Accepted: 06/27/2019] [Indexed: 01/08/2023]
Abstract
Maternal infection and fever during pregnancy have been implicated in the etiology of autism spectrum disorder (ASD); however, studies have not been able to separate the effects of fever itself from the impact of a specific infectious organism on the developing brain. We utilized data from the Study to Explore Early Development (SEED), a case-control study among 2- to 5-year-old children born between 2003 and 2006 in the United States, to explore a possible association between maternal infection and fever during pregnancy and risk of ASD and other developmental disorders (DDs). Three groups of children were included: children with ASD (N = 606) and children with DDs (N = 856), ascertained from clinical and educational sources, and children from the general population (N = 796), randomly sampled from state birth records. Information about infection and fever during pregnancy was obtained from a telephone interview with the mother shortly after study enrollment and maternal prenatal and labor/delivery medical records. ASD and DD status was determined by an in-person standardized developmental assessment of the child at 3-5 years of age. After adjustment for covariates, maternal infection anytime during pregnancy was not associated with ASD or DDs. However, second trimester infection accompanied by fever elevated risk for ASD approximately twofold (aOR = 2.19, 95% confidence interval 1.14-4.23). These findings of an association between maternal infection with fever in the second trimester and increased risk of ASD in the offspring suggest that the inflammatory response to the infectious agent may be etiologically relevant. Autism Res 2019, 12: 1551-1561. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Using data from a large multisite study in the United States-the Study to Explore Early Development-we found that women who had an infection during the second trimester of pregnancy accompanied by a fever are more likely to have children with ASD. These findings suggest the possibility that only more severe infections accompanied by a robust inflammatory response increase the risk of ASD.
Collapse
Affiliation(s)
- Lisa A Croen
- Division of Research, Kaiser Permanente, Oakland, California
| | - Yinge Qian
- Division of Research, Kaiser Permanente, Oakland, California
| | - Paul Ashwood
- Department of Medical Microbiology and Immunology, University of California, Davis, California
| | - Ousseny Zerbo
- Division of Research, Kaiser Permanente, Oakland, California
| | - Diana Schendel
- Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH; National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark.,Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark
| | | | | | - Susan Levy
- Department of Developmental and Behavioral Pediatrics, Philadelphia, Pennsylvania, USA
| | - Laura A Schieve
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Marshalyn Yeargin-Allsopp
- National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Katherine R Sabourin
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Jennifer L Ames
- Division of Research, Kaiser Permanente, Oakland, California
| |
Collapse
|
|
36
|
Walsh LK, Donelle J, Dodds L, Hawken S, Wilson K, Benchimol EI, Chakraborty P, Guttmann A, Kwong JC, MacDonald NE, Ortiz JR, Sprague AE, Top KA, Walker MC, Wen SW, Fell DB. Health outcomes of young children born to mothers who received 2009 pandemic H1N1 influenza vaccination during pregnancy: retrospective cohort study. BMJ 2019; 366:l4151. [PMID: 31292120 PMCID: PMC6614795 DOI: 10.1136/bmj.l4151] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVE To determine whether any association exists between exposure to 2009 pandemic H1N1 (pH1N1) influenza vaccination during pregnancy and negative health outcomes in early childhood. DESIGN Retrospective cohort study. SETTING Population based birth registry linked with health administrative databases in the province of Ontario, Canada. PARTICIPANTS All live births from November 2009 through October 2010 (n=104 249) were included, and children were followed until 5 years of age to ascertain study outcomes. MAIN OUTCOME MEASURES Rates of immune related (infectious diseases, asthma), non-immune related (neoplasms, sensory disorders), and non-specific morbidity outcomes (urgent or inpatient health services use, pediatric complex chronic conditions) were evaluated from birth to 5 years of age; under-5 childhood mortality was also assessed. Propensity score weighting was used to adjust hazard ratios, incidence rate ratios, and risk ratios for potential confounding. RESULTS Of 104 249 live births, 31 295 (30%) were exposed to pH1N1 influenza vaccination in utero. No significant associations were found with upper or lower respiratory infections, otitis media, any infectious diseases, neoplasms, sensory disorders, urgent and inpatient health services use, pediatric complex chronic conditions, or mortality. A weak association was observed between prenatal pH1N1 vaccination and increased risk of asthma (adjusted hazard ratio 1.05, 95% confidence interval 1.02 to 1.09) and decreased rates of gastrointestinal infections (adjusted incidence rate ratio 0.94, 0.91 to 0.98). These results were unchanged in sensitivity analyses accounting for any potential differential healthcare seeking behavior or access between exposure groups. CONCLUSIONS No associations were observed between exposure to pH1N1 influenza vaccine during pregnancy and most five year pediatric health outcomes. Residual confounding may explain the small associations observed with increased asthma and reduced gastrointestinal infections. These outcomes should be assessed in future studies.
Collapse
Affiliation(s)
- Laura K Walsh
- Better Outcomes Registry & Network, Ottawa, ON, Canada
- University of Ottawa, Ottawa, ON, Canada
| | | | | | - Steven Hawken
- University of Ottawa, Ottawa, ON, Canada
- ICES, Toronto, ON, Canada
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Kumanan Wilson
- University of Ottawa, Ottawa, ON, Canada
- ICES, Toronto, ON, Canada
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Eric I Benchimol
- University of Ottawa, Ottawa, ON, Canada
- ICES, Toronto, ON, Canada
- Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
| | - Pranesh Chakraborty
- University of Ottawa, Ottawa, ON, Canada
- Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
| | - Astrid Guttmann
- ICES, Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
- Hospital for Sick Children, Toronto, ON, Canada
| | - Jeffrey C Kwong
- ICES, Toronto, ON, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
- Public Health Ontario, Toronto, ON, Canada
- Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada
| | | | - Justin R Ortiz
- University of Maryland School of Medicine, Baltimore, MD, USA
| | - Ann E Sprague
- Better Outcomes Registry & Network, Ottawa, ON, Canada
- University of Ottawa, Ottawa, ON, Canada
- Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
| | | | - Mark C Walker
- Better Outcomes Registry & Network, Ottawa, ON, Canada
- University of Ottawa, Ottawa, ON, Canada
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Shi Wu Wen
- University of Ottawa, Ottawa, ON, Canada
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Deshayne B Fell
- University of Ottawa, Ottawa, ON, Canada
- ICES, Toronto, ON, Canada
- Children's Hospital of Eastern Ontario (CHEO) Research Institute, Ottawa, ON, Canada
| |
Collapse
|
|
37
|
|
|
38
|
Key role of soluble epoxide hydrolase in the neurodevelopmental disorders of offspring after maternal immune activation. Proc Natl Acad Sci U S A 2019; 116:7083-7088. [PMID: 30890645 DOI: 10.1073/pnas.1819234116] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
Maternal infection during pregnancy increases risk of neurodevelopmental disorders such as schizophrenia and autism spectrum disorder (ASD) in offspring. In rodents, maternal immune activation (MIA) yields offspring with schizophrenia- and ASD-like behavioral abnormalities. Soluble epoxide hydrolase (sEH) plays a key role in inflammation associated with neurodevelopmental disorders. Here we found higher levels of sEH in the prefrontal cortex (PFC) of juvenile offspring after MIA. Oxylipin analysis showed decreased levels of epoxy fatty acids in the PFC of juvenile offspring after MIA, supporting increased activity of sEH in the PFC of juvenile offspring. Furthermore, expression of sEH (or EPHX2) mRNA in induced pluripotent stem cell-derived neurospheres from schizophrenia patients with the 22q11.2 deletion was higher than that of healthy controls. Moreover, the expression of EPHX2 mRNA in postmortem brain samples (Brodmann area 9 and 40) from ASD patients was higher than that of controls. Treatment with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent sEH inhibitor, in juvenile offspring from prenatal day (P) 28 to P56 could prevent cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial PFC of adult offspring after MIA. In addition, dosing of TPPU to pregnant mothers from E5 to P21 could prevent cognitive deficits, and social interaction deficits and PV immunoreactivity in the medial prefrontal cortex of juvenile offspring after MIA. These findings suggest that increased activity of sEH in the PFC plays a key role in the etiology of neurodevelopmental disorders in offspring after MIA. Therefore, sEH represents a promising prophylactic or therapeutic target for neurodevelopmental disorders in offspring after MIA.
Collapse
|
|
39
|
Brown AS, Meyer U. Maternal Immune Activation and Neuropsychiatric Illness: A Translational Research Perspective. Am J Psychiatry 2018; 175:1073-1083. [PMID: 30220221 PMCID: PMC6408273 DOI: 10.1176/appi.ajp.2018.17121311] [Citation(s) in RCA: 197] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Epidemiologic studies, including prospective birth cohort investigations, have implicated maternal immune activation in the etiology of neuropsychiatric disorders. Maternal infectious pathogens and inflammation are plausible risk factors for these outcomes and have been associated with schizophrenia, autism spectrum disorder, and bipolar disorder. Concurrent with epidemiologic research are animal models of prenatal immune activation, which have documented behavioral, neurochemical, neuroanatomic, and neurophysiologic disruptions that mirror phenotypes observed in these neuropsychiatric disorders. Epidemiologic studies of maternal immune activation offer the advantage of directly evaluating human populations but are limited in their ability to uncover pathogenic mechanisms. Animal models, on the other hand, are limited in their generalizability to psychiatric disorders but have made significant strides toward discovering causal relationships and biological pathways between maternal immune activation and neuropsychiatric phenotypes. Incorporating these risk factors in reverse translational animal models of maternal immune activation has yielded a wealth of data supporting the predictive potential of epidemiologic studies. To further enhance the translatability between epidemiology and basic science, the authors propose a complementary approach that includes deconstructing neuropsychiatric outcomes of maternal immune activation into key pathophysiologically defined phenotypes that are identifiable in humans and animals and that evaluate the interspecies concordance regarding interactions between maternal immune activation and genetic and epigenetic factors, including processes involving intergenerational disease transmission. [AJP AT 175: Remembering Our Past As We Envision Our Future October 1857: The Pathology of Insanity J.C. Bucknill: "In the brain the state of inflammation itself either very quickly ceases or very soon causes death; but when it does cease it leaves behind it consequences which are frequently the causes of insanity, and the conditions of cerebral atrophy." (Am J Psychiatry 1857; 14:172-193 )].
Collapse
Affiliation(s)
- Alan S. Brown
- New York State Psychiatric Institute, Columbia University Medical Center, New York, NY
| | - Urs Meyer
- Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Zurich, Switzerland,Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland
| |
Collapse
|
|
40
|
Littauer EQ, Skountzou I. Hormonal Regulation of Physiology, Innate Immunity and Antibody Response to H1N1 Influenza Virus Infection During Pregnancy. Front Immunol 2018; 9:2455. [PMID: 30420854 PMCID: PMC6215819 DOI: 10.3389/fimmu.2018.02455] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 10/04/2018] [Indexed: 12/13/2022] Open
Abstract
In 2009, the H1N1 swine flu pandemic highlighted the vulnerability of pregnant women to influenza viral infection. Pregnant women infected with influenza A virus were at increased risk of hospitalization and severe acute respiratory distress syndrome (ARDS), which is associated with high mortality, while their newborns had an increased risk of pre-term birth or low birth weight. Pregnant women have a unique immunological profile modulated by the sex hormones required to maintain pregnancy, namely progesterone and estrogens. The role of these hormones in coordinating maternal immunotolerance in uterine tissue and cellular subsets has been well researched; however, these hormones have wide-ranging effects outside the uterus in modulating the immune response to disease. In this review, we compile research findings in the clinic and in animal models that elaborate on the unique features of H1N1 influenza A viral pathogenesis during pregnancy, the crosstalk between innate immune signaling and hormonal regulation during pregnancy, and the role of pregnancy hormones in modulating cellular responses to influenza A viral infection at mid-gestation. We highlight the ways in which lung architecture and function is stressed by pregnancy, increasing baseline inflammation prior to infection. We demonstrate that infection disrupts progesterone production and upregulates inflammatory mediators, such as cyclooxygenase-2 (COX-2) and prostaglandins, resulting in pre-term labor and spontaneous abortions. Lastly, we profile the ways in which pregnancy alters innate and adaptive cellular immune responses to H1N1 influenza viral infection, and the ways in which these protect fetal development at the expense of effective long-term immune memory. Thus, we highlight advancements in the field of reproductive immunology in response to viral infection and illustrate how that knowledge might be used to develop more effective post-infection therapies and vaccination strategies.
Collapse
Affiliation(s)
- Elizabeth Q Littauer
- Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, United States.,Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States
| | - Ioanna Skountzou
- Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, United States.,Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, United States
| |
Collapse
|
|
41
|
Diagnostic and Severity-Tracking Biomarkers for Autism Spectrum Disorder. J Mol Neurosci 2018; 66:492-511. [DOI: 10.1007/s12031-018-1192-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Accepted: 09/25/2018] [Indexed: 01/06/2023]
|
|
42
|
Influenza Vaccinations for All Pregnant Women? Better Evidence Is Needed. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:ijerph15092034. [PMID: 30231471 PMCID: PMC6164291 DOI: 10.3390/ijerph15092034] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 08/23/2018] [Accepted: 09/14/2018] [Indexed: 02/07/2023]
Abstract
Pregnant women are a World Health Organization (WHO) priority group for influenza vaccination, but evidence of effectiveness and safety for pregnant women comes from observational studies, which are notoriously prone to confounding by indication and healthy-vaccinee bias. The latter type of bias leads to an overestimation of the effectiveness and safety of the vaccine, which may be what occurs in pregnant women. Indeed, better educated women with healthier behaviors and who seek better medical care may be more adherent to vaccinations recommended by doctors, scientific societies and health authorities. Therefore, it is fundamental to obtain information about vaccine effectiveness and safety from randomized controlled trials (RCTs). Cochrane reviews have identified only one RCT with "low risk of bias". Its results were unclear in terms of maternal, perinatal, and infant deaths and hospitalization, and showed a Number Needed to Vaccine (NNV) of 55 for mothers, with an excess of local adverse effects. A Cochrane review concluded that the inactivated influenza vaccine provides pregnant women with uncertain or very limited protection against influenza-like illnesses and influenza. Some observational studies have suggested possible adverse effects of the inflammation following the vaccination. Consistent with the Cochrane reviewers' conclusions, further trials for influenza vaccines with appropriate study designs and comparison groups are required before promoting universal seasonal influenza vaccinations of pregnant women. Meanwhile, vaccination in second to third trimester should be offered while communicating the uncertainties that still exist, promoting informed choices. Vaccination in the first trimester is debatable and debated. This does not mean leaving women defenseless; many other useful behavioral and environmental measures can reduce infectious disease.
Collapse
|
|
43
|
Becerra-Culqui TA, Getahun D, Chiu V, Sy LS, Tseng HF. Prenatal Tetanus, Diphtheria, Acellular Pertussis Vaccination and Autism Spectrum Disorder. Pediatrics 2018; 142:peds.2018-0120. [PMID: 30104424 DOI: 10.1542/peds.2018-0120] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/30/2018] [Indexed: 11/24/2022] Open
Abstract
UNLABELLED : media-1vid110.1542/5803567555001PEDS-VA_2018-0120Video Abstract BACKGROUND: Increasing vaccination of pregnant women makes it important to assess safety events potentially linked to prenatal vaccination. This study investigates the association between prenatal tetanus, diphtheria, acellular pertussis (Tdap) vaccination and autism spectrum disorder (ASD) risk in offspring. METHODS This is a retrospective cohort study of mother-child pairs with deliveries January 1, 2011 to December 31, 2014 at Kaiser Permanente Southern California hospitals. Maternal Tdap vaccination from pregnancy start to delivery date was obtained from electronic medical records. A diagnosis of ASD was obtained by using International Classification of Diseases, Ninth and Tenth Revision codes. Children were managed from birth to first ASD diagnosis, end of membership, or end of follow-up (June 30, 2017). Cox proportional hazards models estimated the unadjusted and adjusted hazard ratios (HRs) for the association between maternal Tdap vaccination and ASD, with inverse probability of treatment weighting to adjust for confounding. RESULTS Women vaccinated were more likely to be Asian American or Pacific Islander, be nulliparous, have a higher education, receive influenza vaccination prenatally, and give birth at term. ASD was diagnosed in 1341 (1.6%) children, and the incidence rate was 3.78 per 1000 person years in the Tdap exposed and 4.05 per 1000 person years in the unexposed group (HR: 0.98, 95% confidence interval: 0.88-1.09). The inverse probability of treatment weighting-adjusted analyses revealed that prenatal Tdap vaccination was not associated with an increased ASD risk (HR: 0.85, 95% confidence interval: 0.77-0.95). CONCLUSIONS Prenatal Tdap vaccination was not associated with an increased ASD risk. We support recommendations to vaccinate pregnant women to protect infants, who are at highest risk of death after pertussis infection.
Collapse
Affiliation(s)
- Tracy A Becerra-Culqui
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California
| | - Darios Getahun
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California
| | - Vicki Chiu
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California
| | - Lina S Sy
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California
| | - Hung Fu Tseng
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California
| |
Collapse
|
|
44
|
Traglia M, Croen LA, Jones KL, Heuer LS, Yolken R, Kharrazi M, DeLorenze GN, Ashwood P, Van de Water J, Weiss LA. Cross-genetic determination of maternal and neonatal immune mediators during pregnancy. Genome Med 2018; 10:67. [PMID: 30134952 PMCID: PMC6106874 DOI: 10.1186/s13073-018-0576-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 08/03/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control. METHODS This is the first genetic study of > 700 mother-infant pairs to analyse the circulating levels of 22 maternal mid-gestational serum-derived and 42 neonatal bloodspot-derived immune mediators (cytokines/chemokines) in the context of maternal and fetal genotype. We first estimated the maternal and fetal genome-wide SNP-based heritability (h2g) for each immune molecule and then performed genome-wide association studies (GWAS) to identify specific loci contributing to individual immune mediators. Finally, we assessed the relationship between genetic immune determinants and ASD outcome. RESULTS We show maternal and neonatal cytokines/chemokines displaying genetic regulation using independent methodologies. We demonstrate that novel fetal loci for immune function independently affect the physiological levels of maternal immune mediators and vice versa. The cross-associated loci are in distinct genomic regions compared with individual-specific immune mediator loci. Finally, we observed an interaction between increased IL-8 levels at birth, autism spectrum disorder (ASD) status, and a specific maternal genotype. CONCLUSIONS Our results suggest that maternal and fetal genetic variation influences the immune system during pregnancy and at birth via distinct mechanisms and that a better understanding of immune factor determinants in early development may shed light on risk factors for developmental disorders.
Collapse
Affiliation(s)
- Michela Traglia
- Department of Psychiatry and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA
| | - Lisa A Croen
- Divison of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Karen L Jones
- Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California Davis, Davis, CA, USA
- MIND Institute, University of California Davis, Davis, CA, USA
| | - Luke S Heuer
- Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California Davis, Davis, CA, USA
- MIND Institute, University of California Davis, Davis, CA, USA
| | - Robert Yolken
- Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Martin Kharrazi
- Division of Environmental and Occupational Disease Control, California Department of Public Health, Richmond, CA, USA
| | - Gerald N DeLorenze
- Divison of Research, Kaiser Permanente Northern California, Oakland, CA, USA
| | - Paul Ashwood
- MIND Institute, University of California Davis, Davis, CA, USA
- Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, USA
| | - Judy Van de Water
- Department of Internal Medicine, Division of Rheumatology, Allergy, and Clinical Immunology, University of California Davis, Davis, CA, USA
- MIND Institute, University of California Davis, Davis, CA, USA
| | - Lauren A Weiss
- Department of Psychiatry and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
| |
Collapse
|
|
45
|
Lord C, Elsabbagh M, Baird G, Veenstra-Vanderweele J. Autism spectrum disorder. Lancet 2018; 392:508-520. [PMID: 30078460 PMCID: PMC7398158 DOI: 10.1016/s0140-6736(18)31129-2] [Citation(s) in RCA: 1089] [Impact Index Per Article: 155.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2017] [Revised: 04/19/2018] [Accepted: 05/02/2018] [Indexed: 12/20/2022]
Abstract
Autism spectrum disorder is a term used to describe a constellation of early-appearing social communication deficits and repetitive sensory-motor behaviours associated with a strong genetic component as well as other causes. The outlook for many individuals with autism spectrum disorder today is brighter than it was 50 years ago; more people with the condition are able to speak, read, and live in the community rather than in institutions, and some will be largely free from symptoms of the disorder by adulthood. Nevertheless, most individuals will not work full-time or live independently. Genetics and neuroscience have identified intriguing patterns of risk, but without much practical benefit yet. Considerable work is still needed to understand how and when behavioural and medical treatments can be effective, and for which children, including those with substantial comorbidities. It is also important to implement what we already know and develop services for adults with autism spectrum disorder. Clinicians can make a difference by providing timely and individualised help to families navigating referrals and access to community support systems, by providing accurate information despite often unfiltered media input, and by anticipating transitions such as family changes and school entry and leaving.
Collapse
Affiliation(s)
- Catherine Lord
- Center for Autism and the Developing Brain, NewYork-Presbyterian Hospital, Weill Cornell Medicine, Cornell University, White Plains, NY, USA.
| | - Mayada Elsabbagh
- Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada
| | - Gillian Baird
- Evelina Children's Hospital, King's Health Partners, London, UK
| | - Jeremy Veenstra-Vanderweele
- Division of Child and Adolescent Psychiatry, Center for Autism and the Developing Brain, NewYork-Presbyterian Hospital, Department of Psychiatry, Columbia University, New York State Psychiatric Institute, White Plains, NY, USA
| |
Collapse
|
|
46
|
Willsey AJ, Morris MT, Wang S, Willsey HR, Sun N, Teerikorpi N, Baum TB, Cagney G, Bender KJ, Desai TA, Srivastava D, Davis GW, Doudna J, Chang E, Sohal V, Lowenstein DH, Li H, Agard D, Keiser MJ, Shoichet B, von Zastrow M, Mucke L, Finkbeiner S, Gan L, Sestan N, Ward ME, Huttenhain R, Nowakowski TJ, Bellen HJ, Frank LM, Khokha MK, Lifton RP, Kampmann M, Ideker T, State MW, Krogan NJ. The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders. Cell 2018; 174:505-520. [PMID: 30053424 PMCID: PMC6247911 DOI: 10.1016/j.cell.2018.06.016] [Citation(s) in RCA: 81] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 05/07/2018] [Accepted: 06/08/2018] [Indexed: 12/11/2022]
Abstract
Although gene discovery in neuropsychiatric disorders, including autism spectrum disorder, intellectual disability, epilepsy, schizophrenia, and Tourette disorder, has accelerated, resulting in a large number of molecular clues, it has proven difficult to generate specific hypotheses without the corresponding datasets at the protein complex and functional pathway level. Here, we describe one path forward-an initiative aimed at mapping the physical and genetic interaction networks of these conditions and then using these maps to connect the genomic data to neurobiology and, ultimately, the clinic. These efforts will include a team of geneticists, structural biologists, neurobiologists, systems biologists, and clinicians, leveraging a wide array of experimental approaches and creating a collaborative infrastructure necessary for long-term investigation. This initiative will ultimately intersect with parallel studies that focus on other diseases, as there is a significant overlap with genes implicated in cancer, infectious disease, and congenital heart defects.
Collapse
Affiliation(s)
- A Jeremy Willsey
- Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA.
| | - Montana T Morris
- Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Sheng Wang
- Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Helen R Willsey
- Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Nawei Sun
- Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Nia Teerikorpi
- Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Tetrad Graduate Program, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Tierney B Baum
- Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Gerard Cagney
- School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin 4, Ireland
| | - Kevin J Bender
- Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Tejal A Desai
- Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Deepak Srivastava
- Gladstone Institutes, San Francisco, CA 94158, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Graeme W Davis
- Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Jennifer Doudna
- Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA
| | - Edward Chang
- Department of Neurological Surgery, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Vikaas Sohal
- Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Daniel H Lowenstein
- Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Hao Li
- Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA
| | - David Agard
- Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Michael J Keiser
- Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Brian Shoichet
- Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Mark von Zastrow
- Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Lennart Mucke
- Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone Institutes, San Francisco, CA 94158, USA
| | - Steven Finkbeiner
- Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone Institutes, San Francisco, CA 94158, USA; Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Li Gan
- Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone Institutes, San Francisco, CA 94158, USA
| | - Nenad Sestan
- Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06510, USA
| | - Michael E Ward
- National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892, USA
| | - Ruth Huttenhain
- Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Tomasz J Nowakowski
- Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA; The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Hugo J Bellen
- Departments of Molecular and Human Genetics and Neuroscience, Neurological Research Institute at TCH, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA
| | - Loren M Frank
- Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA
| | - Mustafa K Khokha
- Pediatric Genomics Discovery Program, Departments of Pediatrics and Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
| | - Richard P Lifton
- Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY 10065, USA
| | - Martin Kampmann
- Institute for Neurodegenerative Diseases, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA
| | - Trey Ideker
- Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
| | - Matthew W State
- Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94143, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA
| | - Nevan J Krogan
- Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
| |
Collapse
|
|
47
|
Shalev H, Solt I, Chodick G. Month of birth and risk of autism spectrum disorder: a retrospective cohort of male children born in Israel. BMJ Open 2017; 7:e014606. [PMID: 29150463 PMCID: PMC5702026 DOI: 10.1136/bmjopen-2016-014606] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Increased incidence and prevalence of autism spectrum disorder (ASD) over the last two decades have prompted considerable efforts to investigate its aetiological factors. We examined an association between month of birth and ASD incidence. METHODS In a retrospective cohort of male children born from January 1999 to December 2008 in a large health organisation in Israel (Maccabi Healthcare Services), ASD was followed from birth through December 2015. RESULTS Of 108 548 boys, 975 cases of ASD were identified. The highest rates (10.3 and 10.2 per 1000 male live births) were recorded for children born in May and August, respectively, and the lowest rates for February (7.6 per 1000 male live births). Among lower socioeconomic status households, boys born in August were more likely (OR=1.71; 95% CI 1.06 to 2.74) of being diagnosed with ASD than children born in January. Significantly higher rates were not observed for other months. CONCLUSIONS In line with several previous studies, we found a modestly higher likelihood of autism occurrence among male children of lower socioeconomic levels born in August.
Collapse
Affiliation(s)
| | - Ido Solt
- Faculty of Medicine,Technion, Haifa, Israel
- Rambam Health Care campus, Haifa, Israel
| | - Gabriel Chodick
- Maccabi Healthcare Services, Tel Aviv, Israel
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| |
Collapse
|
|
48
|
Kagashe I, Yan Z, Suheryani I. Enhancing Seasonal Influenza Surveillance: Topic Analysis of Widely Used Medicinal Drugs Using Twitter Data. J Med Internet Res 2017; 19:e315. [PMID: 28899847 PMCID: PMC5617904 DOI: 10.2196/jmir.7393] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2017] [Revised: 06/09/2017] [Accepted: 07/26/2017] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Uptake of medicinal drugs (preventive or treatment) is among the approaches used to control disease outbreaks, and therefore, it is of vital importance to be aware of the counts or frequencies of most commonly used drugs and trending topics about these drugs from consumers for successful implementation of control measures. Traditional survey methods would have accomplished this study, but they are too costly in terms of resources needed, and they are subject to social desirability bias for topics discovery. Hence, there is a need to use alternative efficient means such as Twitter data and machine learning (ML) techniques. OBJECTIVE Using Twitter data, the aim of the study was to (1) provide a methodological extension for efficiently extracting widely consumed drugs during seasonal influenza and (2) extract topics from the tweets of these drugs and to infer how the insights provided by these topics can enhance seasonal influenza surveillance. METHODS From tweets collected during the 2012-13 flu season, we first identified tweets with mentions of drugs and then constructed an ML classifier using dependency words as features. The classifier was used to extract tweets that evidenced consumption of drugs, out of which we identified the mostly consumed drugs. Finally, we extracted trending topics from each of these widely used drugs' tweets using latent Dirichlet allocation (LDA). RESULTS Our proposed classifier obtained an F1 score of 0.82, which significantly outperformed the two benchmark classifiers (ie, P<.001 with the lexicon-based and P=.048 with the 1-gram term frequency [TF]). The classifier extracted 40,428 tweets that evidenced consumption of drugs out of 50,828 tweets with mentions of drugs. The most widely consumed drugs were influenza virus vaccines that had around 76.95% (31,111/40,428) share of the total; other notable drugs were Theraflu, DayQuil, NyQuil, vitamins, acetaminophen, and oseltamivir. The topics of each of these drugs exhibited common themes or experiences from people who have consumed these drugs. Among these were the enabling and deterrent factors to influenza drugs uptake, which are keys to mitigating the severity of seasonal influenza outbreaks. CONCLUSIONS The study results showed the feasibility of using tweets of widely consumed drugs to enhance seasonal influenza surveillance in lieu of the traditional or conventional surveillance approaches. Public health officials and other stakeholders can benefit from the findings of this study, especially in enhancing strategies for mitigating the severity of seasonal influenza outbreaks. The proposed methods can be extended to the outbreaks of other diseases.
Collapse
Affiliation(s)
- Ireneus Kagashe
- School of Management and Economics, Beijing Institute of Technology, Beijing, China
| | - Zhijun Yan
- School of Management and Economics, Beijing Institute of Technology, Beijing, China
- Sustainable Development Research Institute for Economy and Society of Beijing, Beijing, China
| | - Imran Suheryani
- School of Life Science, Department of Biomedical Engineering, Beijing Institute of Technology, Beijing, China
| |
Collapse
|
|
49
|
Brucato M, Ladd-Acosta C, Li M, Caruso D, Hong X, Kaczaniuk J, Stuart EA, Fallin MD, Wang X. Prenatal exposure to fever is associated with autism spectrum disorder in the boston birth cohort. Autism Res 2017; 10:1878-1890. [PMID: 28799289 DOI: 10.1002/aur.1841] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 07/04/2017] [Accepted: 07/12/2017] [Indexed: 12/25/2022]
Abstract
Autism spectrum disorder (ASD) is phenotypically and etiologically heterogeneous, with evidence for genetic and environmental contributions to disease risk. Research has focused on the prenatal period as a time where environmental exposures are likely to influence risk for ASD. Epidemiological studies have shown significant associations between prenatal exposure to maternal immune activation (MIA), caused by infections and fever, and ASD. However, due to differences in study design and exposure measurements no consistent patterns have emerged revealing specific times or type of MIA exposure that are most important to ASD risk. No prior studies have examined prenatal MIA exposure and ASD risk in an under-represented minority population of African ancestry. To overcome these limitations, we estimated the association between prenatal exposure to fever and maternal infections and ASD in a prospective birth cohort of an understudied minority population in a city in the United States. No association was found between prenatal exposure to genitourinary infections or flu and the risk of ASD in a nested sample of 116 ASD cases and 988 typically developing controls in crude or adjusted analyses. Prenatal exposure to fever was associated with increased ASD risk (aOR 2.02 [1.04-3.92]) after adjustment for educational attainment, marital status, race, child sex, maternal age, birth year, gestational age, and maternal smoking. This effect may be specific to fever during the third trimester (aOR 2.70 [1.00-7.29]). Our findings provide a focus for future research efforts and ASD prevention strategies across diverse populations. Autism Res 2017, 10: 1878-1890. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY We looked at whether activation of the immune system during pregnancy increases the chance a child will develop ASD. We examined 116 children with ASD and 988 children without ASD that came from a predominantly low income, urban, minority population. We found that having the flu or genitourinary tract infections during pregnancy is not related to the child being diagnosed with ASD. However, we did find children were at increased risk for ASD when their mothers had a fever during pregnancy.
Collapse
Affiliation(s)
- Martha Brucato
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205.,Johns Hopkins University School of Medicine, Medical Scientist Training Program, Baltimore, MD, 21205.,Johns Hopkins Bloomberg School of Public Health, The Wendy Klag Center for Autism and Developmental Disabilities, Baltimore, MD, 21205
| | - Christine Ladd-Acosta
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205
| | - Mengying Li
- Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, The Center on the Early Life Origins of Disease, Baltimore, MD, 21205
| | - Deanna Caruso
- Johns Hopkins Bloomberg School of Public Health, The Wendy Klag Center for Autism and Developmental Disabilities, Baltimore, MD, 21205.,Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, The Center on the Early Life Origins of Disease, Baltimore, MD, 21205
| | - Xiumei Hong
- Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, The Center on the Early Life Origins of Disease, Baltimore, MD, 21205
| | - Jamie Kaczaniuk
- Johns Hopkins Bloomberg School of Public Health, The Wendy Klag Center for Autism and Developmental Disabilities, Baltimore, MD, 21205
| | - Elizabeth A Stuart
- Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205
| | - M Daniele Fallin
- Johns Hopkins Bloomberg School of Public Health, The Wendy Klag Center for Autism and Developmental Disabilities, Baltimore, MD, 21205.,Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205
| | - Xiaobin Wang
- Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, The Center on the Early Life Origins of Disease, Baltimore, MD, 21205
| |
Collapse
|
|
50
|
Vaccine opponents' use of Twitter during the 2016 US presidential election: Implications for practice and policy. Vaccine 2017; 35:4670-4672. [DOI: 10.1016/j.vaccine.2017.06.066] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 06/16/2017] [Accepted: 06/21/2017] [Indexed: 11/21/2022]
|